Dynamic changes of naïve T cells determine mature T cells activity in cell-mediated immune response. It is important to understand the mechanism of homeostasis maintenance affect response to novel antigen toward T cell receptor-major histocompatibility complex interaction. Most of the analysis of naïve T cells relies on flow cytometric immunophenotyping to observe surface antigen alteration within maturation stage. The combination of different surface molecules, such as the cluster of differentiation 62L (CD62L), C-C chemokine receptor type 7 (CCR7), CD27, CD28, and CD45, can give satisfied discrimination between naïve T cells and other subsets. This parameter can be used to monitor the dynamic change of naïve T cells in some chronic diseases, like human immunodeficiency virus (HIV) and cytomegalovirus (CMV). Most of the patient experience loss of naive T cells due to a chronic immune response, which related to apoptotic induction in proliferating cells by viral activity. Some pathogens trigger the migration of naive T cells into lymph nodes to facilitate direct contact with the host cells. The virus infects the cells, use cells proliferation to multiply, and induce apoptosis of host cells after the virions released. Alteration of naive T cells in chronic disease becomes a parameter to oversee the treatment and to determine the future prognosis of the disease. In highly active antiretroviral therapy for HIV infection, observation of naïve T cells and combination of surface molecules, CD45RO− and CD27+ is used to show the improvement and proliferation rate of total naïve T cells. On the other hand, the transformation of naïve T cells into CMV-specific T cells become really important in CMV prognosis. These conditions suggest that dynamic change of naïve T cells affect to the clinical condition of chronic disease patients.Keywords: naïve T cells, immunophenotyping, HIV, CMV

Background: Chemotherapy is a common treatment for leukemia as well as in other cancer treatment. The lack of tumor selectivity and development of multi-drug resistance by chemotherapy caused the development of new strategy in cancer treatment become a pressing need. This study was performed to evaluate the anticancer activity and selectivity of seven derivatives of chalcones against K562 and HL-60 leukemia cell lines. Materials and Methods: The cytotoxicity of chalcone’s seven derivatives (compound 1-7) was tested by using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxyme-thoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) method. The percentage of cell mortality data was calculated then the IC50 was analyzed using probit analysis (SPSS 17). The selectivity index (SI) then calculated from IC50 ratio of normal lymphocyte cells and cancerous cells line (HL-60 and K562).Results: The IC50 of almost all seven tested compounds were lower in HL-60 cell lines than K562 cell lines, except for Compound 7. The number and position of methoxy groups in chalcone derivatives influenced the anticancer and cancer selectivity of chalcone derivatives.Conclusion: The results revealed that the number and position of methoxy groups in chalcone derivatives influenced the anticancer and cancer selectivity of chalcone derivatives.Keywords: anticancer, chalcone derivatives, methoxy-4’-amino chalcone, leukemia, cytotoxic, selectivity

Background: One of the conditions for releasing standardized herbal medicines is the presence of pre-clinical testing that can be conducted with mice. Emulsion products with the main composition of pumpkin, red palm oil, and dragon fruit have high levels of β-carotene. The purpose of this study was to observe changes in weight, cholesterol, and sub-chronic toxicity from mice treated with emulsion products.Materials and Methods: Mice observed consisted of 6 groups: (1) untreated control (given standard ration); (2) negative control (given standard ration and 2.8% (v/b) egg yolk); (3) positive control (given standard ration and 0.4% (v/b) β-carotene); (4) standard ration, 0.4% (v/b) β-carotene and 2.8% (v/b) egg yolk; (5) given a standard ration and 2% (v/b) emulsion products; and (6) given a standard ration, 2% (v/b) emulsion products and 2.8% (v/b) egg yolk. Observations of sub-chronic toxicity were done by measuring creatinine levels, kidney weight, and visual observation of kidney swelling.Results: The use of β-carotene-rich emulsions does not cause a decrease in the average weight of mice. In general, β-carotene and emulsion can overcome cholesterol increases on the 7th day, but not for the 15th day as a result of standard food intake. The increase in creatinine levels only occurs in mice treated with egg yolk control. The additional treatment of β-carotene and emulsion successfully prevents the increase in creatinine levels.Conclusion: Emulsion products did not cause changes in weight, were able to reduce cholesterol levels in a limited manner and were not toxic to mice.Keywords: cholesterol changes, sub-chronic toxicity, b-carotene, emulsion

Background: Malnutrition and tuberculosis (TB) have a bidirectional relationship, which interacts between each other. In chronic infection, there is an imbalance between protein degradation and protein synthesis which marked with the loss of fat-free mass (FFM). Malnutrition can cause the atrophy of the thymus gland resulted in the reduction of lymphocyte production. Malnutrition in TB patients will reduce the quality of life. On the other hand, a good quality of life will increase the treatment success rate and decrease the risk of morbidity and mortality. Materials and Methods: A cross-sectional study was conducted in 12 primary health centers (PHC) chosen randomly from 23 PHC in Pekanbaru, Riau Province. The random selection was performed by using simple random sampling (random number generator). Data were collected from May until July 2019. Samples were selected using a consecutive sampling method and 72 subjects fulfilled all research criteria. The interview was used to collect basic characteristic data, dietary intake data, and quality of life score. Anthropometric measurement (body weight, body height, and FFM) and laboratory examination (total lymphocyte count) were done.Results: Research showed median age subjects was 33 years old (18-59 years old). Most of the subjects were male (56.9%), had a middle level of education, low income, were active smokers with underweight nutritional status. More than 50% of subjects had low protein intake, low fat-free mass, normal lymphocyte count and had a good quality of life.Conclusion: There was a statistically significant correlation between fat-free mass with PCS (r=0.239, p=0.044), but not for protein intake and total lymphocyte count.Keywords: fat-free mass, protein, quality of life, total lymphocyte count, tuberculosis

Background: Leptin resistance which leads to excessive circulating leptin levels is thought to affect ovarian function. This study aimed to study the correlation between serum leptin levels with insulin resistance in patients with polycystic ovary syndrome.Materials and Methods: This cross-sectional study was undertaken in several teaching hospitals in Makassar, Indonesia. We included patients diagnosed with polycystic ovary syndrome (PCOS) aged 18-40 years old. Serum leptin levels were examined in all eligible subjects using the enzyme-linked immunosorbent assay (ELISA) method. The results obtained were further analyzed statistically.Results: Approximately 53 PCOS subjects were included in this study, 25 subjects with insulin resistance and 28 subjects without insulin resistance. After examining serum leptin levels, we found that leptin is directly proportional to insulin resistance (p<0.001). We even found a strong positive correlation between serum leptin levels with homeostatic model assessment for insulin resistance (HOMA-IR) levels (r=0.659; p<0.001). Leptin was found to be independent of HOMA-IR, not influenced by confounding factors such as body mass index (BMI) (p=0.090).Conclusion: There was a significant correlation between serum leptin levels and HOMA-IR values in PCOS patients. This correlation was found to be significant regardless of patient's BMI, therefore is considered to have a direct effect on insulin resistance in PCOS.Keywords: polycystic ovary syndrome, leptin, insulin resistance, HOMA-IR

Background: The major significant factor that affected lung cancer development among female passive smokers is environmental tobacco smoke. Nicotine can be found in a never smoker population, such as a child whose father is a smoker. Lung carcinogenesis in never smoker populations is affected by nicotine metabolism by CYP2A6 gene, which encodes the main nicotine metabolizing-enzyme. The aim of this study was to assess the genetic polymorphism of CYP2A6 and its association with secondhand smokers among females who have suffered from lung cancer in North Sumatra population.Materials and methods: This study was a case-control study, composed of 53 case subjects and 46 control subjects that were involved through a purposive sampling technique from two hospitals in Medan. PCR-RFLP was used for the examination of CYP2A6 gene to determine the genotype. The data were analyzed with conditional logistic regression test using Epi Info 7.0 software.Results: The most common genotype of CYP2A6 detected in this study was *1B/*1B (40.4%), while *1B allele had the highest prevalence (55.5%). There was no significant association between CYP2A6 genotype (p-value=0.61) or alleles (p-value=0.25) and the incidence of lung cancer.Conclusion: There was no association between CYP2A6 polymorphism and the incidence of lung cancer in secondhand smoker females.Keywords: CYP2A6, PCR-RFLP, female secondhand smokers, lung cancer

Background: Currently, the key to combat coronavirus disease 2019 (COVID-19) as a global pandemic is relying mainly on vaccination, and several factors might affect the level of protection. This study aimed to determine the quantitative increase of neutralizing antibody titer against COVID-19 and the influence of gender, body mass index (BMI), routine consumption of vitamin C, D, and E towards the neutralizing antibodies after vaccination.Materials and methods: One hundred nine health workers from various health facilities were recruited. Sinovac inactivated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine was used in this study. Antibody titer measurements were carried out quantitatively using electrochemiluminescence immunoassay (ECLIA) on day 14 after the first and second doses administration of the vaccine.Results: The average of antibody titers after the first and second doses were 109.1 and 191.6 U/mL, respectively. Antibody titer significantly increased (p=0.000) as much as 82.5 U/mL from the first to the second dose. There was a significant difference in the increase in antibody titer between respondents who consumed vitamin E regularly and those who did not (p=0.036). Routine consumption of vitamin C and D, gender, and BMI did not affect the increase in neutralizing antibody titer with p-values of 0.983, 0.337, 0.186, and 0.424, respectively.Conclusion: Routine consumption of vitamin E is associated with post-SARS-CoV-2 vaccination neutralizing antibody response. Gender, BMI, and the routine consumption of vitamin C and D have no association with the immune response.Keywords: COVID-19, neutralizing antibody, inactivated SARS-CoV-2 vaccine

Background: SARS-CoV-2 virus uses angiotensin converting enzyme 2 (ACE2), a key enzyme of the renin angiotensin system (RAS) as the functional receptor for cell fusion and induction of infections in the respiratory system. Functional ACE2 gene polymorphisms may lead to RAS imbalance and are associated with COVID-19 susceptibility and severity. ACE2 G8790A (rs2285666), a splice region variant, is well characterized in various populations across the world. In the present study, the role of ACE2 G8790A (rs2285666) variant as risk predictor for severity of COVID-19 infection was investigated.Materials and methods: One-hundred COVID-19 subjects were included in the study and divided into: subjects with a history of severe infection and ICU-admitted (Group 1) and subjects with mild to moderate COVID-19 infection (Group 2). Genotype analysis for rs2285666 of ACE2 was performed using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method.Results: The distribution of ACE2 G8790A (rs2285666) genotypes were GG 62%, GA 18%, and AA 20% in Group 1 and GG 34%, GA 14%, and AA 52% in Group 2, respectively. The A allele of rs2285666 (p≤0.001; OR=3.4; 95% CI=1.89–6.107) were less frequent in Group 1 as compared to Group 2. Also, a statistically significant difference was found between severity of COVID-19 infection with age and comorbidities such as diabetes, hypertension, chronic kidney disease, but not gender.Conclusion: Our findings suggest the possibility of a protective mechanism of the AA genotype of ACE2 G8790A (rs2285666) variant against COVID-19 disease severity.Keywords: COVID-19, ACE2 gene, renin-angiotensin system, genetic association, rs2285666, sanger sequencing

The rapid aging of the global population is a major worldwide issue because of the close relationship between age and the development of several diseases. Aging or senescence is among the most widely studied topics at the moment. However, no pharmaceuticals have been developed that claim to possess anti-senescence properties. Andrographis paniculata, is a medicinal plant found widely throughout tropical and subtropical Asia. This review aims to identify the potential anti- senescence effect of A. paniculata extract and its bioactive compounds. By following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, five databases were used and in vivo and in vitro studies were included in this review. A. paniculata extracts and their bioactive compounds exert anti-senescence properties through their anti-inflammatory and antioxidant properties. This herb and its compounds enhanced memory, cognitive function and behaviour in Alzheimer's disease. The extract also promoted cell cycle progression and proliferation in the skin. In addition, andrographolide exhibited anti-senescence effects in endothelial cells through the activation of PI3K/Akt/Nrf and PI3K/Akt/AP-1 pathways. A. paniculata along with its bioactive compounds including andrographolide and 14-deoxyandrographolide, may have the potential to be used as anti-senescence through anti-inflammatory and antioxidant properties. However, the specific markers to evaluate the senescence are necessary to be conducted. Any clinical trials should be done to establish these findings. Since in clinical settings this potential herbal may be used for long-life time, the safety profile and toxicity of A. paniculata should be considered. Keywords: herbal plants, Andrographis paniculata, andrographolide, bioactive compounds, senescence

Background: The anting-anting plant (Acalypha indica L.) is used in herbal medicine in the treatment of various diseases. The leaf extract of this plant is known for its antimicrobial activity, but the antimicrobial properties of the endophytic bacteria within its leaves have never been reported. This research aims to determine the antimicrobial activity of endophytic bacteria from the leaves of the anting-anting plant. Materials and methods: The isolation of endophytic bacteria was performed using the spread plate method on nutrient agar (NA) media. Following isolation, the bacterial isolates were characterized through macroscopic and microscopic examination, as well as biochemical tests, which included indole production, hydrogen sulfide (H2S) production, motility, Simmons citrate utilization, methyl red-Voges-Proskauer (MR-VP) test, catalase test, and triple sugar iron agar (TSIA) test. Identification of the bacterial isolates was conducted according to Bergey's Manual of Systematic Bacteriology. Additionally, the antimicrobial activity of the isolates was assessed using the diffusion methodResults: Fourteen isolates of anting-anting leaf endophytic bacteria were obtained (coded as BEDA 1 to BEDA 14). The BEDA 5 isolate exhibited the largest inhibitory zone diameter against Staphylococcus aureus (31.48 mm), while BEDA 9 showed a significant inhibitory zone diameter against Candida albicans (17.84 mm). Conclusion: The two isolates (BEDA 5 and BEDA 9) exhibited significant antimicrobial activity, indicating their potential as promising candidates for alternative antimicrobial agents. These results suggest that endophytic bacteria from Acalypha indica may play an essential role in combating antibiotic resistance and in the development of new therapeutic strategies.Keywords: endophytic bacteria, characterization, antimicrobial activity, Acalypha indica

Lung cancer is the most contributor of cancer cause death in the world. Lung cancer is related to cigarette consumption and genetic factor. Nicotine derived nitrosamine ketone is the most important inducer of lung cancer associated with DNA Mutations resulting in the activation of Kirsten rat sarcoma viral (KRAS) oncogenes. DNA Mutation in Lung cancer is mostly presence by epidermal growth factor receptor (EGFR) mutations. There were seven potential biomarkers to detect early lung cancer, whereas carcinoembryonic antigen (CEA), neuron specific enolase (NSE), cytokeratin-19 fragments (CYFRA 21-1), alpha-fetoprotein (AFP), cancer antigen 125 (CA-125), CA-199 and ferritin. The use of biomarkers in combination can improve the accuracy in diagnosing lung cancer. Other biomarkers include KRAS mutations, B-type Raf kinase (BRAF) mutation, mesenchymal-epithelial transition factor (MET) amplification and Excision repair cross-complementing group 1 (ERCC1) can be used to see whether there are any genetic mutations that lead to lung cancer. Treatment of lung cancer with chemotherapy can be done using tyrosine kinase inhibitors and monoclonal antibodies.Keywords: lung cancer, DNA mutation, EGFR, KRAS, BRAF, MET, tyrosine kinase 

Background: John Cunningham Virus (JCV) was involved in pre-malignant lessions and carcinogenesis of the colon. The purpose of this study was to detect and analyze JCV T-Ag expression in mild and severe dysplasia adenomatous polyp as well as low and high grade adenocarcinoma of the colon.Materials and Methods: This study used analytic descriptive, cross sectional approach. The samples’ paraffin blocks were taken from colon adenomatous polyp cases (all grades of dysplasia) and cases of colon adenocarcinoma (all degrees) at Anatomical Pathology Laboratory, School of Medicine, Atma Jaya Catholic University of Indonesia from 2010-2014 (5 years period). Samples were reviewed from HE slides to determine histopathologic diagnosis, grades of dysplasia and grading. We performed immunohistochemistry staining with monoclonal antibody anti–SV 40-T-Ag to detect JCV T-Ag expression.Results: We found 7 cases of colon adenomatous polyp, of which 4 (57%) were mild dysplasia and 3 (43%) were severe dysplasia. Positive expression of JCV T-Ag was detected in 1 (14%) mild dysplasia case. Data analysis using Fischer’s Exact Test was p>0.05. We also found 16 cases of colon adenocarcinoma. 14 cases (87.5%) of low grade variant and 2 cases (12.5%) of high grade variant. Positive expression of JCV T-Ag was detected in 2 (12.5%) low grade cases. Data analysis using Fischer’s Exact Test was p>0.05.Conclusion: There was no difference of JCV T-Ag expression in colon adenomatous polyp (mild-severe dysplasia) and colon adenocarcinoma (low-high grade) cases at Anatomical Pathology Laboratory School of Medicine, Atma Jaya Catholic University of Indonesia 2010-2014.Keywords: colon adenomatous polyp, adenocarcinoma, JCV T-Ag

Background: Sugar palm fruit (Arenga pinnata) is used for osteoarthritis empirically. It also has antioxidant activity and showed inhibition to lipoxygenase activity. The study about analgesic and anti-inflammatory activities of sugar palm fruit is still limited, this study was initiated to explore analgesic and anti-inflammatory effects of sugar palm fruit ethanol extract (SFEE).Materials and Methods: Acetic acid induced writhing was performed for screening analgesic activity, meanwhile antiinflammatory activity was tested against rat paw edema. Acute toxicity and phytochemical screening were also investigated.Results: The results of phytochemical screening revealed that flavonoids, alkaloids and quinones were present in SFEE. SFEE 50 and 100 mg/kg have analgesic effect and show the anti-oedematogenic effect against paw edema induced by carrageenan. SFEE could significantly decrease the neutrophils numbers as compared to the carrageenan-treated group. Neutrophil activation has been shown to contribute to tissue inflammation and damage.Conclusion: SFEE have analgetic and anti-inflammatory activity.Keywords: Arenga pinnata, analgesic, anti-inflammatory, acute toxicity

Background: World Health Organization (WHO) has reported the antimicrobial resistance as one among the ten threats to global health in 2019. The development of plant-derived antibiotics is currently considered as a modern medicine’s greatest success. Persea americana is a plant with high medicinal profile which allow its different parts to be used for therapeutic purposes. This study is aimed to determine the antibacterial potential of ethanol and chloroform extracts from epicarp of mature fruits of P. americana Mill against human pathogens.Materials and Methods: The epicarps of avocado were dried in oven and ground into powder using porcelain mortar and pestle. The powdered plant materials were extracted with both 96% ethanol and chloroform. Extracts were qualitatively screened to examine their bioactive contents and agar well diffusion method was used to analyze the antibacterial activity of extracts against both Gram-positive and Gram-negative bacteria.Results: Both solvents showed the ability to dissolve the secondary metabolites from avocado epicarps. Phytochemical screening disclosed the presence of alkaloids, proteins, terpenoids, tannins, flavonoids, steroids and phenolic compounds in ethanolic extracts and absence of flavonoids and tannins in chloroform extracts. The extracts showed the inhibition zones ranging from 14±4.5 mm to 26±2.1 mm while streptomycin demonstrated high inhibition zones ranging from 20±3.1 mm to 30 mm. The minimum inhibitory concentration (MIC) values of extracts ranges from 0.3125 mg/mL to 20 mg/mL while the MIC values for streptomycin vary from 0.25 mg/mL to 1.25 mg/mL.Conclusion: The ethanol and chloroform extracts proved to be potentially effective as natural alternative preventives to fight against various disease-causing bacteria.Keywords: antibacterial activity, ethanol extract, chloroform extract, Persea americana, Rwanda

Background: Non-alcoholic steatohepatitis (NASH) is an expanding cause of chronic liver disease worldwide, including Indonesia, with higher risk progression to cirrhosis and hepatocellular carcinoma. Preclinical experiments using several mice models have been conducted to clarify its complex pathogenesis. This study was designed to investigate whether BALB/c mice on a choline-deficient high-fat diet can be used as a model for NASH. Materials and Methods: BALB/c male mice were fed choline-deficient L-amino acid-defined high-fat diet (CDAHFD) or a standard diet for six weeks. The body and liver weights, liver histology, and plasma biochemistry were analyzed. The relative expression levels of tumor necrosis factor (TNF)α, transforming growth factor (TGF)β1, collagen-1α1 (COL1α1), glutathione peroxidase 1 (GPx1), and uncoupling protein 2 (UCP2) genes in the livers were analyzed using a two-step real time-polymerase chain reaction. Liver fatty acids composition was analyzed using gas chromatography with flame ionization detector (GC-FID). Results: CDAHFD induced steatohepatitis in BALB/c mice with increased plasma levels of alanine aminotransferase. The liver of CDAHFD-fed BALB/c mice showed upregulated relative expression levels of TNFα, TGFβ1, COL1α1, GPx1, and UCP2 genes. The liver fatty acid analysis showed a significant accumulation of saturated fatty acids (SFAs) and an increased ratio of n-6/n-3 polyunsaturated fatty acids (PUFAs) in the livers of CDAHFD-fed BALB/c mice. Conclusion: This study suggests that CDAHFD can induce steatohepatitis in BALB/c mice and therefore may be used as NASH mice model.Keywords: steatohepatitis, fatty liver, choline-deficient high fat diet, BALB/c 

Background: Prostatic anomalies are common in tumor or infection condition. The enlargement of prostate gland affects the epithelial cell polarity that involves epithelial-mesenchymal transition (EMT). Transition into mesenchymal is mediated by transcription factor ZEB1 and E-cadherin protein. Upregulation of ZEB1 and loss of E-Cadherin expression were associated to proliferation and metastasis of malignancy cells. This study aims to describe the correlation of ZEB1 and E-cadherin expression in prostatic anomaly.Materials and method: Samples were Formalin Fixed Paraffin Embedded (FFPE) block consist of 8 block Benign Prostatic Hyperplasia (BPH), 6 blocks High Grade Prostatic Intraepithelial Neoplasia (HGPIN) and 6 blocks Prostate Carcinoma (PCA). The blocks then sliced into 5 sections to be prepared for RNA extraction procedures. ZEB1 and E-Cadherin expression was analyzed by semi-quantitative procedures using PCR and electrophoresis. Correlation between ZEB1 and E-Cadherin espression was analyzed using Spearman’s rank correlation.Results: Relative expression of ZEB1 and E-cadherin mRNA in each group of prostatic anomaly were not significantly different (p>0.05). ZEB1 and E-Cadherin mRNA expression showed a significant and moderate level of negative correlation (p<0.05; 0.40 < r < 0.59). Increasing of ZEB1 mRNA expression will be followed by decreasing of E-Cadherin mRNA expression.Conclusion: ZEB1 negatively correlates with E-cadherin due to EMT process in prostatic anomaly. High expression of ZEB1 induced down-regulation of E-cadherin and vise versa. Various studies can be developed, especially the development of targeted therapy against ZEB1 to suppress the EMT process by increasing the expression of E-cadherin.Keywords: epithelial-mesenchymal transition (EMT), ZEB1, E-Cadherin, BPH, HGPIN, PCA

Background: Coronavirus disease 2019 (COVID-19) in children spreads easily and has a relatively high incidence. Severe complications in children confirmed with COVID-19 are thought to be related to the multisystem inflammatory syndrome, which is associated with coagulation disorders. D-dimer is a fibrin degradation end product which is easy to examine, affordable, fast and reliable. This study investigated the potency of D-dimer levels as a biomarker and assessed optimal cut-off value of D-dimer on severity of COVID-19 in children. Materials and methods: An analytical observational study with a cross-sectional design was conducted in children aged 1-18 years confirmed to have mild, moderate or severe COVID-19 who were treated in the isolation room of Dr. Moewardi Hospital, Surakarta, Indonesia from September 2021 to February 2022. Statistical analysis was conducted using Mann- Whitney test and p<0.05 was considered as statistically significant. The cut-off value of D-dimer was determined with the receiver operating characteristic (ROC) curve. Results: There were 39 children with COVID-19. They were in mild (n=14; 35.9%), moderate (n=19; 48.7%) and severe (n= 6; 15.4%) stages. There were significant differences in D-dimer levels between mild and moderate stages (p=0.001), and mild and severe stages (p=0.001). No significant difference in D-dimer levels between moderate and severe stages (p=0.162). The cut-off value of D-dimer was 485 μg/mL with 92% sensitivity and 71.4% specificity. Conclusion: D-dimer can be used as a potential biomarker of severity in children with COVID-19.Keywords: D-dimer, COVID-19, severity, children

Autoimmune hemolytic anemia (AIHA) is a rare condition in which autoantibodies cause the loss of red blood cells. Steroids have been used to treat several illnesses, including AIHA. For now, steroids remain as the first line of treatment for AIHA. In AIHA, especially warm AIHA (wAIHA), steroids suppress autoantibody production and downregulate Fcγ receptors' expression on monocytes to prevent hemolysis. The type of steroids chosen for first-line therapy for wAIHA in pediatrics and adults are Prednisone (Prednisolone) and Methylprednisolone. At the same time, Dexamethasone is used as an alternative treatment in AIHA. Steroids show better therapeutic outcomes in the first 2-3 weeks of administration, but the proportion of patients who remain in remission after steroid discontinuation are still quite low. Long-term administration of steroids may affect bone, blood glucose metabolism, and hypothalamic-pituitary-adrenal axis (HPAA). However, steroids which have a linear pharmacokinetic profile, intermediate-acting glucocorticoids such as Prednisone (Prednisolone) or Methylprednisolone, and also tapering dose of steroids after 2-4 weeks administration will be safe for long term use as AIHA treatment.Keywords: steroids, glucocorticoid, corticosteroid, autoimmune hemolytic anemia, AIHA, mechanism of action, efficacy

Glioblastoma multiforme (GBM), a highly aggressive and malignant form of brain cancer, continues to pose a significant challenge in the field of oncology. Despite ongoing advancements in treatment strategies, the prognosis for GBM patients remains grim, with a 5-year survival rate hovering around 5%. The management of GBM involves multiple therapeutic approaches, including immunotherapy, but optimal treatment outcomes in terms of overcoming tumor recurrence and resistance have not been achieved. A key factor contributing to therapy resistance and the progression of GBM is the tumor's ability to evade the immune system, referred to as immune escape from cancer. This phenomenon reflects the tumor cells' efforts to adapt and survive the body's immune response. The release and expression of molecules like TGF-ß, IL-10, PD-L1, and NKG2DL by GBM cells impact the activation, recognition, and elimination of tumor cells by the immune system. Additionally, the involvement of cells such as MDSCs, Tregs, and TAMs plays a role in inhibiting the immune system's function, thereby promoting the development of GBM cells. A better comprehension of GBM's immune escape, supported by technological advances, will significantly aid in the future management of GBM patients' treatment.Keywords: glioblastoma multiforme, GBM, cancer immunity, immune evasion, immune escape, immunotherapy

Background: Clinical features of severe coronavirus disease 2019 (COVID-19) predominantly include respiratory symptoms and exacerbated multi-organ complications, especially in patients with comorbidities. Cellular immunity, including lymphocytes, is a critical factor in combating SARS-CoV-2 infection. However, immune dysregulation occurs in severe COVID-19 patients, characterized by cytokine storm and lymphopenia. The effectiveness of mesenchymal stem cell (MSC) therapies for COVID-19 is being assessed. The secretome released by MSC functions similarly to the cells themselves as an immunomodulator, offering potential advantages in terms of safety and cost-effectiveness. This study was conducted to assess the effect of umbilical cord MSC-derived (UC-MSC) secretome treatment on lymphocyte count and soluble programmed cell death-1 (sPD-1) levels in severe COVID-19 patient's whole blood.Materials and methods: Twelve whole blood samples from healthy individuals and severe COVID-19 patients were analyzed for lymphocyte count and functional activation using flow cytometry, along with sPD-1 level measurement in pre-treatment and post-secretome conditions.Results: The lymphocyte count in severe COVID-19 patients was significantly decreased, particularly for T cells and NK cells, indicating lymphopenia. Following secretome treatment, CD4+ T cell counts significantly increased compared to pre-treatment, although this change was not significant in the negative control group. Additionally, there was a minimal reduction in B cell count and an increase in sPD-1 levels. Elevated sPD-1 may alleviate T cell exhaustion by interfering with PD-1 binding to programmed death-ligand 1 (PD-L1).Conclusion: Administration of UC-MSC secretome to the whole blood of severe COVID-19 patients suggested immune improvement, with significant increases in CD4+ T cell counts, enhanced B cell survival, and elevated sPD-1 levels. Keywords: COVID-19, cellular immunity, lymphocytes, secretome, MSC

Background: Alopecia is a condition with partial or complete hair loss, leading to psychological distress. Current treatments, such as minoxidil and finasteride, have limited efficacyand side effects. Recent studies suggest that mesenchymal stem cells (MSCs)-derived exosomes offer regenerative potential by modulating inflammation and enhancing hair follicle regeneration, though optimal dosage remains unclear. Tumor necrosis factor-alpha (TNF-α)  inhibits hair follicle growth, while vascular endothelial growth factor (VEGF) promotes hair regrowth. This study evaluates  exosome therapy from hypoxia (Hypo-Exo)-treated MSCs in modulating TNF-α and VEGF in a fluconazole-induced alopecia-like model..Materials and methods: An experimental post-test only control group design was used with 30 male Wistar rats, divided into five groups:  Healthy group, 0.9% NaCl-treated group, 5% Minoxidil-treated group, 100 μg/mL Hypo-Exo MSCs-treated group, and 200 μg/mL Hypo-Exo MSCs-treated group. TNF-α and VEGF levels were analyzed using ELISA on day 14 post-treatment. Results: The highest TNF-α level was found in the 0.9% NaCl-treated group (307.46 ± 20.68 pg/mL) and significantly reduced (p<0.05) in 100 μg/mL Hypo-Exo MSCs-treated group (65.38±15.05 pg/mL) and 200 μg/mL Hypo-Exo MSCs-treated group (37.16±7.14 pg/mL). VEGF levels were the highest in the 200 μg/mL Hypo-Exo MSCs-treated group (189.11±9.75 pg/mL) and 100 μg/mL Hypo-Exo MSCs-treated group (158.50±5.33 pg/mL), compared to the 0.9% NaCl-treated group (69.60±15.39 pg/mL). Conclusion: Hypo-Exo MSCs significantly reduced TNF-α and increased VEGF levels, supporting their potential as a novel regenerative therapy for alopecia. Keywords: alopecia, TNF-α, VEGF, exosome, hypoxia, mesenchymal stem cells 

Background: Diabetes mellitus is a metabolic disease, characterized by hyperglycemia due to disturbance in both insulin secretion and function. One of theurapeutic approaches is to reduce blood glucose levels by inhbiting α-/β-glucosidase and α-amylase involved in carbohydrate digestion. Thus, inhibition of these enzymes play important role in the treatment of diabetes mellitus. Roselle (Hibiscus sabdariffa L.) has been known to have several medicinal properties and potency as an antidiabetics agents. This reseacrh aimed to observe antidiabetic properties of roselle ethanol extract (REE) towards α-glucosidase, β-glucosidase and α-amylase.Materials and Methods: REE was done with maceration technique using diluent of 70% ethanol. Antidiabetic properties were measured by inhibitory activity of α-amylase, α-glucosidase and β-glucosidase.Results: REE was able to inhibit α-/β-glucosidase and α-amylase in the highest concentration with inhibition percentage of 72.68, 47.34 and 73.08% respectively, and were comparable with Acarbose of 81.49, 50.97, 73.08%. The median inhibitory concentration (IC50) of α-/β-glucosidase and α-amylase of REE were 15.81, 41.77, 18.09 μg/mL respectively, and Acarbose were 9.45, 22.57, 3.64 μg/mL respectively.Conclusions: REE inhibits α-/β-glucosidase and α-amylase.Keywords: Roselle, Acarbose, α-glucosidase, β-glucosidase, α-amylase, antidiabetic

Stroke is a leading cause of death and long-term disability. This due to the ischemic event that cause by embolism of blockage blood flow. Thrombolytic agent plasminogen activator (tPA) is the only treatment approved by FDA. However, the used of tPA is limited to the short time window period. Neural stem cells (NSCs) show the potential to repair neuronal damage naturally after stroke. However, isolating NSCs is a challenging process due to the limitations of the method and its invasiveness. Some studies that had used mesenchymal stem cell (MSCs) as the main source of stem cell for therapy show that MSCs have the potency to differentiate into NSCs. in vitro, a differentiation process from MSC to NSC has been developed by combining the supplement or growth factor needed in the culture media.Keywords: stem cells, neuron stem cell, mesenchymal stem cell, stroke, trans-differentiation

Background: Hasford score is a scoring system which was made in interferon treatment era to assess chronic myelocytic leukemia (CML) prognosis. Complete hematologic response (CHR) is the milestone of prognosis evaluation. CHR achievement will significantly increase survival. Imatinib is a revolutionized treatment that change the prognosis of CML. With the advent of Imatinib, lessened the prognostic impact of the Hasford score to predict prognosis.Materials and Methods: An observational analytic with prospective cohort study conducted in oncology outward division Dr. Soetomo hospital Surabaya, from July until October 2018. Hasford score determined in 32 patients at the beginning of the study, given imatinib and followed up regularly for 3 months to know the hematologic response. Data were analyzed using Fisher exact test which was considered significant if p<0.05.Results: Median age was 39 years old, male 37.5% and female 62.5%, the median spleen was 18 cm, median hemoglobin was 9.1 g/dL, median leukocyte was 180x109 /L, median thrombocyte was 645x109 /L, median eosinophil was 2.9%, median basophil was 4.6%, median myeloblast was 6%. Hasford score showed 3.1% in low risk, 25% in intermediate risk and 71.9% in high risk. As much as 78.1% complete hematologic response was found in patient, and 21.9% was incomplete.Conclusion: There was no association between Hasford scoring system and hematologic response in chronic and accelerated phase of chronic myelocytic leukemia patient with imatinib for three month. Hasford score had no impact in hematologic response with imatinib.Keywords: Hasford score, hematologic response, CML, imatinib

Background: Asthma is a chronic inflammation of the bronchial tree that emerges as a response to exogenous factors, such as allergens, irritants, and infections. Some asthmatic patients had been reported having symptoms of asthma due to house-dust mites (HDM) allergen exposure. It is associated with immune responses which were increased in the form of specific Immunoglobulin E (IgE) production against HDM allergens. This case-control study aimed to determine the HDM profiles in persistent asthmatic patients, including density of mites, as well as its relationship with specific IgE anti-HDM serum levels.Materials and Methods: A total of 13 patients with persistent asthma and 12 control patients had their specific anti-HDM IgE levels examined using Immulite 2000 xpi. The house dust samples were taken and analyzed with the Fain method.Results: The results have shown that 69% of patients in the persistent asthma group and 25% of normal patients were positive for IgE anti-HDM. Dermatophagoides pteronyssinus is a predominant species with a total of 120 mites (83.9%) of 143 mites. Correlation analysis indicated a positive relationship between IgE anti-HDM levels within the serums of patients and the density of mites in the dust obtained from bedroom spaces (Spearmen Rho, R=0.35, p=0.04).Conclusion: Positive IgE anti-HDM patients in the persistent asthma group were higher (69%) than those in the clinically normal group (25%). The density of mites were dominated by D. Pteronyssinus. The bedroom-dust mites density revealed a positive correlation with serum IgE anti-HDM levels in persistent asthma patients.Keywords: asthma, density, Dermatophagoides spp.,IgE

Background: Long-term use of valproic acid is associated with a high level of blood ammonia related to carnitine deficiency. This study investigates the effect of carnitine supplementation on blood ammonia levels in children with epilepsy who have been treated with valproic acid for more than six months.Materials and Methods: This was a randomized, double-blind, placebo-controlled trial study where children with epilepsy who were treated with valproic acid were randomly allocated to the carnitine supplementation and control group. All children were followed for month, and then measured for blood ammonia level. Blood ammonia levels of both groups were compared using an Independent t-test with a significant of p<0.05.Results: Total of 32 children with epilepsy were enrolled as subjects in this study, with 16 children in carnitine group, and 16 children in control group. Among the subjects, 50% were male and 50% were female, with a mean age of 6.5 years old. The average duration of epilepsy in the carnitine and control group were 41.7 months and 36.9 months, respectively (p=0.419). The duration of valproic acid therapy in the carnitine and control group were 33.1 months and 27.6 months, respectively (p=0.483). The level of blood ammonia in carnitine and control group were 44.6 mg/dL and 81.4 mg/dL, respectively (p=0.007).Conclusion: The level of blood ammonia in a carnitine group was significantly lower than in a control group. It is recommended to give carnitine supplementation in epileptic children treating with long-term valproic acid.Keywords: ammonia, carnitine, epilepsy, seizure, valproic acid

Background: Chronic kidney disease (CKD) is a global public health problem, due to the increasing prevalence and incidence of kidney failure, poor prognosis, and required high costs for its treatment. Hypertension as the dominant risk factor for CKD also has a high prevalence which keep increasing in DKI Jakarta. This study aimed to determine the association between hypertension and the incidence of CKD in people aged ≥18 years old in DKI Jakarta Province.Materials and method: This was a quantitative research with an analytic cross-sectional study design. The data source used was secondary data obtained from Basic Health Research (Riset Kesehatan Dasar/Riskesdas) 2018. There were 7,141 samples that matched the inclusion and exclusion criteria.Results: The proportion of CKD and hypertension in people aged ≥18 years old in DKI Jakarta Province were 0.5% and 16.6%, respectively. There was a significant association between hypertension and CKD with a prevalence odds ratio (POR) of 3.140 (95% CI: 1.527-6.453) after being adjusted by the age variable. Several other characteristics such as age (POR = 3.912; 95% CI: 1.932-7.918), diabetes mellitus (POR = 3.412; 95% CI: 1.405-8.285), heart disease (POR = 7.323; 95% CI: 3.158- 16.982), and physical activity (POR = 2.324; 95% CI: 1.148-4.703) were also significantly associated with the incidence of CKD.Conclusion: Someone who has hypertension has 3.14 times (95% CI: 1.527-6.453; p-value = 0.002) chance of suffering from CKD compared to someone who does not have hypertension after being controlled by the confounding variable, age.Keywords: chronic kidney disease, hypertension, DKI Jakarta, Basic Health Research 2018

The experimental research on the use of mesenchymal stem cells (MSCs) for burn therapy has been published several times. However, current clinical procedure remains a challenging discussion. This systematic review assesses the safety and efficacy of administering mesenchymal stem cells (MSCs) to burns and determines the most effective source of MSCs for burn therapy. We reviewed several studies through PubMed, Google Scholar, Science Direct, and DOAJ online databases. PRISMA-P 2020 method was used based on inclusion and exclusion criteria that were re-selected through Joanna Briggs Institute (JBI) Critical Appraisal Tools. Results from 13 articles showed that MSCs are safe for burn therapy with minimal side effects/complications and have the potential to repair tissue and accelerate burn healing through several mechanisms. The treatment of MSCs in burns is influenced by donor characteristics and related to the severity and area of the burn. It can be concluded that the administration of MSCs is safe and effective in burn therapy. Keywords: burns, mesenchymal stem cells, therapeutic safety, therapeutic efficacy, wound healing

Background: Indonesia is the second-highest country with hepatitis B cases in the South East Asian region. Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein 12 (Cas12) could be developed as a diagnostic tool to detect hepatitis B infection. This study was aimed to develop a diagnostic method for hepatitis B virus by designing CRISPR target-based single-guide RNA (sgRNA).Materials and method: The preCore/Core-gene sequences of hepatitis B virus were collected from the National Center for Biotechnology Information (NCBI) website. The selected sequence was submitted to Cas Designer and CRISPOR tools to design sgRNA. The resulting sgRNA was cloned in silico into an expression vector using Benchling software.Results: The 23-nucleotide sequence 5'- GTAGTCAGTTATGTCAATGTTAA-3’ had 30% GC content, 68.3 out-of-frame and 76 predicted efficiencies. This sequence had no mismatch based on analysis.Conclusion: This preliminary study will help design a CRISPR-based diagnostic kit for the detection of hepatitis B virus in Indonesia. However, further in vitro and in vivo studies are required to demonstrate its potential and efficiency.Keywords: CRISPR-Cas12b, diagnostic, HBV, sgRNA 

Background: Obesity is a global epidemic caused by excessive body fat, which is increasing free fatty acids in the liver, causing oxidative stress and liver cell damage. Green tea yogurt (GTY) with encapsulated Lacticaseibacillus paracasei E1 (GTY-LpE1) might have a beneficial effect in reducing liver cell damage. This study was conducted determine GTY-LpE1 effect on superoxide dismutase (SOD) expression, malondialdehyde (MDA) expression and liver histopathology in high-fat high-fructose diet (HFFD) mice. Material and Methods: A completely randomized design (CRD) with 7 groups, including normal diet (ND) group, HFFD group, 1.3 mg/kg BW simvastatin (SIM)-administered HFFD group, 5 g/kg BW probiotic yoghurt (PY)-administered HFFD (PY), 2.5 g/kg BW GTY-administered HFFD (2.5 GTY), 5 g/kg BW GTY-administered HFFD (5 GTY), and 10 g/kg BW GTY-administered HFFD (10 GTY). The diet was given for 16 weeks, followed by oral administration of sim/yoghurt during the last 4 weeks. Mice were sacrificed and the liver was collected. SOD and MDA expression were analyzed by flow cytometry. Histopathology analysis was done by evaluating hematoxylin-eosin (HE) staining of the liver.Result: The percentage of necrotic cells were 34.55, 34.31, and 21.95%, when treated with 2.5, 5, and 10 g/kg BW with GTY-administered HFFD, respectively, these were lower than the ones in the HFFD group (69.49%). The percentage of MDA expression were 15.55, 18.69, and 22.42%, respectively, these were lower than the ones in the HFFD group as well. The percentage of SOD expression were 9.49, 7.85, and 11.11%, respectively, these were higher than the ones in the HFFD group (3.44%). Conclusion: GTY-LpE1 could decrease the number of necrotic cells in the HFFD mice livers and improve the hepatocyte damage by reducing MDA expression and enhancing SOD expression. GTY-LpE1 can be used as an alternative food to control obesity.Keywords: alginate, chitosan, encapsulation, green tea, probiotic

Background: Klebsiella pneumoniae is a major pathogen in pediatric pneumonia. Procalcitonin (PCT) distinguishes between Gram positive and Gram negative infections but lacks data on K. pneumoniae infection's relationship with PCT levels in children. Therefore, this study was conducted to investigate the serum PCT levels in children with K. pneumoniae infection.Materials and methods: A cross-sectional study was conducted on 61 pediatric subjects with the age of 2-59 months with severe bacterial pneumonia. Blood and sputum samples were collected and analyzed for PCT and cultured for 24 hours. PCT levels and K. pneumoniae infection were statistical analyzed with chi-square and logistic regression. Receiver operating characteristic (ROC) analysis was used to determine the PCT cut-off specific to K. pneumoniae. Results: K. pneumoniae was identified in 33%. Median PCT levels were significantly higher in the K. pneumoniae group (p<0.05). A PCT cut-off of 0.725 ng/mL yielded 70% sensitivity, 70.7% specificity, negative predictive value (NPV) of 82.9%, and area under the receiver operating characteristic curve (AUROC) of 0.74. Elevated PCT was significantly associated with K. pneumoniae infection with Odds ratio (OR) of 12.08, 95% Confidence Interval (CI): 2.54-57.36; p=0.002).Conclusion: Along with K. pneumoniae infection, serum PCT levels was elevated, supporting its potential as a biomarker for early diagnosis.    Keywords: K. pneumoniae, procalcitonin, bacterial pneumonia, pediatric

Background: Androgenic alopecia (AGA) is characterized by hair follicle miniaturization and chronic inflammation mediated by dihydrotestosterone (DHT). Current therapies primarily target hormonal pathways and do not adequately address inflammatory dysregulation. Exosomes derived from hypoxia-conditioned mesenchymal stem cells (EH-MSCs) exhibit enhanced immunomodulatory properties. However, their effects on key inflammatory mediators in AGA remain unclear. This study evaluated the effects of EH-MSCs on CXCL12 and IL-10 expression in a DHT-induced AGA mouse model.Materials and methods: Male C57BL/6 mice were allocated into five groups: healthy control, DHT-induced alopecia without treatment, DHT-induced alopecia treated with topical minoxidil, and EH-MSCs administered at 100 or 200 µL/kgBW. Alopecia was induced by subcutaneous DHT injection for 17 days. Following model validation, treatments were administered on days 25 and 32. CXCL12 and IL-10 expression in dorsal skin tissue was analyzed using RT-PCR on day 39.Results: DHT induction significantly increased CXCL12 expression and reduced IL-10 levels (p<0.05). EH-MSC administration dose-dependently downregulated CXCL12 (1.73±0.57 and 1.54±0.44 fold-change) and upregulated IL-10 expression (3.10±0.75 and 3.29±0.67 fold-change), demonstrating greater immunomodulatory effects compared with minoxidil.Conclusion: EH-MSCs effectively modulated inflammatory biomarkers by suppressing CXCL12 and enhancing IL-10 expression in a DHT-induced AGA model, suggesting their potential as an immunoregenerative therapeutic strategy for androgenic alopecia.Keywords: androgenic alopecia, mesenchymal stem cells, exosomes, hypoxia, CXCL12, IL-10

Osteoclast activities are responsible for the resorption of bone cells found in several bone diseases, one of which is periodontitis and arthritis. The downregulating signals of Receptor Activator of Nuclear Factor kB (RANK)-RANK Ligand and Tumor Necrosis Factor  (TNF)-a are the major cause of the bone destruction. Studies and experiments have been performed to overcome this matter. Various medications are now available to treat bone-related diseases, targeting the specific aspect of the signaling. Synthetic drugs such as denosumab and bisphosphonates have complex pharmacological action and have been the leading choice in treatment. Evidence in studies proved that natural resources including herbal products have potential application to therapy for bone loss, with caffeic acid and Caffeic Acid Phenethyl Ester (CAPE) showing significant inhibitory results and Chinese herbs such as Herba epimedii (Yín Yáng Huò) and Fructus psoraleae(Bǔ Gǔ Zhī) proved to contain components that give similar effects to estrogen. The purpose of this review is to discuss the therapy value of available synthetic and natural therapeutic agents. Understanding the mechanisms of both agents will not only clarify their function as therapeutic agents, but can also be the key to the treatment of diseases caused by bone resorption by targeting specific aspects of osteoclastogenesis.Keywords: osteoclastogenesis, TNF, RANKL, bone resorption, natural resource, signaling, treatment

Background: It is important to maintain the adequate level of vitamin B6 to ensure stable metabolism. Vitamin B6 serum level might decreased by absorption disturbance or increasing demand. Valproic acid increase the synthesis of serum GABAergic in the other hand vitamin B6 is required as cofactor for gamma-amino butyric acid (GABA) formation. The dosage and duration of valproic acid therapy might be correlated with vitamin B6 serum level. The aim of this study is to know the correlation between vitamin B6 serum level against dosage and duration of valproic acid therapy in children with epilepsy.Materials and Methods: This is a cross sectional study to investigate the correlation between vitamin B6 serum level against dosage and duration of valproic acid therapy. The level of vitamin B6 serum was determined by checking vitamin B6 active form in serum, pyridoxal 5’-phospate (PLP).Results: In this study, 37 epilepsy children with valproic acid duration therapy more than 3 months was enrolled. Fifty six percent epilepsy children were male, commonly on children age 1-5 years old. Spearman correlation coefficient test showed a significant weak negative correlation between vitamin B6 serum level and dosage of valproic acid (r=–0.35; p=0.03), and very weak negative correlation with valproic acid duration therapy (r=-0.08; p=0.59), however it was not significant. Conclusion: There was a significant weak negative correlation between vitamin B6 serum level and very weak negative correlation with valproic acid duration therapy, but not significant in children with epilepsy.Keywords: correlation, valproic acid, vitamin B6

Background: The excessive free radicals condition called oxidative stress can harmful for the body. To prevent and cure it, the antioxidant agents are required. Nowadays, the natural product extracted from plants have been widely used in folk medicine as antioxidant for the treatment of many diseases. Ficus elastica (rubber tree) has some compounds that has several biological activities, i.e., quercitrin, myricitrin, morin, and eleutheroside B. The F. elastica works against the free radicals and can be potential as antioxidant agent. The purpose of this study was to evaluate antioxidant properties of F. elastica ethanolic extract (FEE), quercitrin, myricitrin, morin, and eleutheroside B.Materials and Methods: The antioxidant activities of FEE and standard compounds were evaluated by free radical-scavenging activity of 2,2-diphenyl-1-picrylhydrazil (DPPH), hydrogen peroxide (H2O2), 2,2’-azinobis-(3-ethylbenzothiazoline- 6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) activities using spectrophotometry method.Results: FEE has the lowest of DPPH scavenging activity (IC50=13.82 µg/mL) than other compounds. In ABTS scavenging activity, FEE has moderate activity with IC50 value 23.29 µg/mL. In FRAP activity, FEE has moderate activity with value 241.58 µM Fe(II)/µg, while in H2O2 scavenging activity, FEE also show moderate activity with IC50=83.97 µg/mL compared to other compounds.Conclusion: In summary, FEE and the pure compounds (quercitrin, myricitrin, morin, and eleutheroside B) have potential as antioxidant agent.Keywords: free radical, morin, myricitrin, quercitrin, rubber tree, scavenging activities

Background: Skin adhesive has been used for attaching certain medical application to the human skin for functional and/or esthetic purposes. Silicone adhesive is the most common type of skin adhesives that are recently used. This study aims to evaluate the possible effect of humidity on the performance of silicone skin adhesive.Materials and Methods: Twenty-four silicone samples were divided into 2 main groups based on relative humidity (RH) exposure, namely 43% RH and 98% RH. Six samples from each group were tested for adhesion strength after 1 hour of adhesion, and the other 6 samples were tested after 2 hours of adhesion by conducting 180 degree peel test. The data were statistically analyzed for significant difference. Results: The results showed that at 43% RH, the adhesion strength was higher than the 98% RH group. The results also showed that at both humidity settings the adhesion strength after the first hours of adhesion was lower than the adhesion strength after the second hour.Conclusion: The silicone skin adhesive performance can be affected by the increase of relative humidity which needs more time of application to skin to reach the best adhesion function.Keywords: adhesions strength, humidity effect on adhesion, silicone adhesive, skin adhesives

Background: Infusate of the whole plant of Physalis angulata is used traditionally for the remedy of various diseases including diabetes and gout. This study focused on the stem of P. angulata. The objectives of this study were to investigate the potential of the stem infusate (INPA) and ethanol extract (EEPA) of P. angulata as inhibitors of α-glucosidase and xanthine oxidase.Materials and Methods: INPA and EEPA were determined for their α-glucosidase and xanthine oxidase inhibition activities in vitro, whereas antioxidant activity was determined by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay. Reference inhibitors were used for comparison. The total phenolic compounds were also estimated.Results: EEPA had more concentrated phenolic than INPA which were 7.96 and 0.08 mgGAE/g dried biomass, respectively. INPA and EEPA inhibited α-glucosidase considerably, with IC50 of 149.11 and 409.86 µg/mL, respectively (acarbose was 130.66 µg/mL). However, they inhibited xanthine oxidase weakly, with IC50 of 0.546 and 2.643 mg/mL, respectively, compared with allopurinol 0.005 mg/mL. EEPA scavenged DPPH radicals very weakly (16.04 mg/mL) compared to BHT (0.021 mg/mL), whereas no activity was observed for INPA.Conclusion: The stem infusate and ethanol extract of P. angulata are able to inhibit the activity of α-glucosidase, thus can be further explored for sources of bioactive compounds with α-glucosidase inhibition activity.Keywords: α-glucosidase, infusate, ethanol extract, Physalis angulata, stem, xanthine oxidase

Background: Preeclampsia remains as the leading cause of maternal-neonatal mortality and morbidity worldwide. Vascular endothelial growth factor A (VEGF-A) is a proangiogenic factor related to endothelial dysfunction and plays an important role in the preeclampsia pathophysiology. Genetic variants of VEGF-A are associated with VEGF-A expression and preeclampsia risk, however there are still inconsistent results between different populations. The aim of this study was to determine the association of this genetic variant as preeclampsia risk factor.Materials and methods: A cross-sectional study was performed with 76 pregnant women (29 preeclampsia and 47 normotensive) Jambi-Malay ethnic subjects. Sample DNA was extracted from subject’s blood. To determine the genotype, one-step tetra amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) method for VEGF-A rs699947 C/A was used.Results: We found that pregnant woman with AC genotype (p-value=0.045; OR=2.76 ; 95% CI=1.01-7.58) and AA genotype (p-value=0.026; OR=12.44; 95% CI=1.23-126.18) had higher risk of preeclampsia than the CC genotype.Conclusion: Genetic variant VEGF-A rs699947 C/A is associated with preeclampsia. The AC and AA genotype is the risk genotype for preeclampsia in Jambi-Malay ethnics.Keywords: preeclampsia, VEGF-A, genetic variant, Jambi-Malay, Indonesia

Ovarian granulosa cell tumor (GCT) is a rare low-grade malignancy condition. One type of GCT is adult GCT (AGCT), which has the tendency for late recurrence. AGCT is clinically palpable and focally cystic and solid. In this case report, a condition of recurrent ovarian cancer after laparotomy debulking surgery was reported. A 57-year-old woman, who was diagnosed with AGCT, had a history of laparotomy debulking three months prior and complained of abdominal pain and enlargement, along with significant weight loss. Ultrasound examination revealed a solid cyst, raising suspicion of recurrent ovarian cancer. Laboratory results indicated elevated CA-125 levels. Histopathology results confirmed metastasis of AGCT, after the second laparotomy debulking was done. Recurrence of GCT is uncommon within three months of debulking. In this rare condition, we suggested a laparotomy debulking and adjuvant chemotherapy as a treatment. Effectiveness of treatment of recurrent disease is an independent risk factor to reduce the risk of another relapse and increase the survival rate.Keywords: granulosa cell tumor, ovarian cancer, debulking

Myocardial infarction is one of the leading causes of death worldwide. Current treatments do not compensate for the loss of cardiomyocytes, thus progression to heart failure is often inevitable. In myocardial infarction, the occlusion of coronary arteries and sudden restoration of blood flow give rise to ischemia-reperfusion injury, which leads to cardiomyocyte death. Mitochondria are not only involved in the bioenergetic aspect of the heart but also play a pivotal role in cell death during ischemia-reperfusion injury. Their morphology dynamically changes via fusion and fission in a balanced manner to maintain cellular health. However, ischemia-reperfusion injury triggers excessive mitochondrial fission, which is pathological to the myocardium. This review article discusses the association between myocardial ischemia-reperfusion injury and mitochondrial dynamics, serving as a rationale for a novel therapeutic strategy for myocardial infarction. Strategic modulation of mitochondrial dynamics under this pathological setting has been shown to be effective for cardioprotection. Increasing mitochondrial fusion or reducing excessive mitochondrial fission in the myocardial tissue could prevent cardiomyocyte death, thereby reducing infarct size. Proof-of-concept studies have utilized small molecules and peptides to implement this strategy into in vivo myocardial ischemia-reperfusion injury models. However, there remains a need to address the issues of specificity, bioavailability, and potency of these pharmacological agents before future application in cardiovascular therapeutics. Nevertheless, there has been growing interest in this therapeutic strategy in recent years, rendering it an attractive approach for ischemia-reperfusion injury in the heart.Keywords: mitochondria, heart, ischemia-reperfusion, cardioprotection

Background: Hyperpigmentation is often exacerbated by ultraviolet-B (UVB) exposure through oxidative stress and activation of pathways like mitogen-activated protein kinase (MAPK) and vascular endothelial growth factor receptor (VEGFR). Current treatments carry risks and necessitate safer alternatives. This study investigated the therapeutic potential of hypoxia-induced mesenchymal stem cell (MSC) exosomes in reducing protein kinase-A (PKA) and VEGFR expression in UVB-induced hyperpigmentation.Materials and methods: A post-test-only control group design was used with 30 male C57BL/6 mice divided into five groups: Healthy group, 0,9% NaCl-treated group, retinol-treated group, and two treatment groups (200 µL Exosomes-treated group and 300 µL Exosomes-treated group. UVB-induced hyperpigmentation was established with 180 mJ/cm² exposures over two weeks. Treatment was administered via subcutaneous injections for seven days. PKA and VEGFR mRNA levels were analyzed using qRT-PCR.Results: PKA expression was significantly lower in the 200 µL Exosomes-treated group (0.34±0.05) and 300 µL Exosomes-treated group (0.21±0.04) groups compared with the 0,9% NaCl-treated group (1.12±0.08) (p<0.001). VEGFR expression similarly decreased in 200 µL Exosomes-treated group (0.32±0.05) and 300 µL Exosomes-treated group (0.18±0.04) versus the 0,9% NaCl-treated group (1.48±0.09) (p<0.001). Both exosome doses achieved reductions comparable to baseline levels observed in the Healthy group.Conclusion: Hypoxia-induced MSC exosomes reduced PKA and VEGFR expression in UVB-induced hyperpigmentation, with the 300 µL dose showing greater efficacy. These findings suggested exosome therapy as a promising alternative for hyperpigmentation treatment. Keywords: hyperpigmentation, MSC, PKA, VEGFR, melanin

Based on American Diabetes Association (ADA), diabetes can be classified into the following general categories: type 1 diabetes (T1D), type 2 diabetes (T2D), gestational diabetes mellitus (GDM) and specific types of diabetes due to other cause. Obesity is by far the main underlying factor causing T2D and its pathological potential lies in obesity-associated insulin resistance, activation of innate immunity and chronic low-grade inflammation. When tissue inflammation induced, tissue destruction occurs, 'self' antigens, which are generally not accessible to T cells, can be released from the affected tissues and promote autoimmune activation. The 4 major autoantibodies are islet-cell cytoplasmic autoantibodies (ICA), glutamid acid decarboxylase antibody (GADA), islet antigen-2 antibody (IA-2A) and insulin autoantibodies (IAA). In addition, ZnT8A has recently been found to predict T1D. ZnT8 is contained in the islets of Langerhans, with the highest expression is in β cells of the pancreas. ZnT8A measurements simultaneously with GADA, IA-2A and IAA achieve rates of 98% detection for onset level of autoimmune diabetes. Presence of antibodies in T2D also shows the potential serious complications compared with T2D without antibodies. The combination of GADA, IA-2A and ZnT8A can be suggested as the most powerful and cost-effective diagnostic approach in patients with T1D.Keywords: autoantibody, autoimmune, diabetes mellitus, ICA, GADA, IA-2A, IAA, ZnT8A

Background: Malaria is still a universal health problem, especially in tropical countries because of high morbidity and mortality rates. Infection by Plasmodium falciparum and Plasmodium vivax could result in asymptomatic disease of malaria and be found in Trenggalek, Jawa Timur. Differences in pathogenesis among affected individuals are affected by many factors, and the immune system is one of them. Among substances involved in the malarial immunity is Tumor Necrosis Factor (TNF)-α and Interleukin (IL)-10, produced by the body's defense system as the reaction to the parasite. Therefore a study was designed to detect the level of TNF-α and IL-10 in asymptomatic malaria patients.Materials and Methods: A cross-sectional study was conducted. Thirty male asymptomatic malaria subjects, age 21 to 60 years were selected. Blood from each subject was collected and the levels of TNF-α and IL-10 were analyzed using enzyme-linked immunosorbent assay (ELISA) method. Significant values considered at p<0.05.Results: There was an increased level of TNF-α with the average of 218.760 pg/µL, and an increased level of IL-10 with an average of 257.574 pg/µL in asymptomatic malaria subjects. In normal person IL-10 level is 12.6 (8.5-16.7) pg/mL and the levels of TNF-α in normal person is 0-1.5 pg/mL because they are not produce. There was a positive correlation of TNF-α with IL-10 (r=0.332; p>0.05), and positive correlation between TNF-α and the rate of hemoglobin (r=0.002; p>0.05). IL-10 was correlated negatively with the rate of hemoglobin (r=-0.363; p<0.05).Conclusion: The results from this study conclude that TNF-α and IL-10 levels increase in asymptomatic malaria subjects.Keywords: asymptomatic malaria, TNF-α, IL-10, parasite, hemoglobin

Background: Inflammation is a body response caused by injury and infection. Pulpitis is a pulp tissue inflammation which is the continuous process of pulp hyperemia by bacteria invasion. Myrmecodia pendans or Sarang semut is known to contain flavonoid compound which has the anti inflammation effect. The purpose of this study is to investigate the effect of Myrmecodia pendans ethanol extract on the healing process of pulp inflammation.Materials and Methods: This experimental study involved pre- and post-in vivo treatment of 27 Sprague Dawley rats in which the inducted pulpitis model was obtained by injecting 0.01 mL Porphyromonas gingivalis into the dental pulp for 48 hours. Subjects were divided randomly into Group I (negative control), Group II (pulpitis treated by Myrmecodia pendans extract ethanol as treatment group), and Group III (pulpitis treated by Ca(OH)2 as positive control group). Group II and III as pulpitis treatment groups were divided into subgroups based on the induction periods of 48 hours (2 days), 168 hours (7 days), and 366 hours (14 days). All specimens were processed into the slides and evaluated microscopically for the healing process.Results: The result of this study showed significant difference (p<0.05) among groups on day 2, 4 and 7. On day 4, the pulpitis treatment group of Myrmecodia pendans extract showed better healing process than Ca(OH)2. On day 7, the pulpitis treatment group of Ca(OH)2 showed better healing process than Myrmecodia pendans extract. On day 14, both of the pulpitis treatment groups showed normal pulp.Conclusion: Myrmecodia pendans ethanol extract is effective for the healing process of inflamed pulp.Keywords: inflamed pulp, Myrmecodia pendans, sarang semut, Ca(OH)2 , healing process

Cancer constitutes of complex heterogeneous organ-like structures with a hierarchical cell structure, and only minor phenotypic subpopulations with stem-like properties have a dual capacity to indefinitely self-renew and generate all heterogeneous cell phenotypes consisting of bulk tumor cells. Cancer stem cells (CSC) has similar properties to ordinary stem cells. It is understood that CSC is responsible for the recurrence of metastasis and drug resistance. Thus, control of CSC can provide successful therapy intervention that inhibits cancer growth and aggressive behavior. Conventional cancer therapy is realized to be insufficient for oral cancer therapy. Meanwhile, accurate targeting of OCSC has proved to be a significant challenge due to the commonality of many markers between OCSC and healthy cells. This article discusses the current understanding of oral CSC, with focus on origin, stemness, marker and signalling pathway.Keywords: oral cancer stem cell, CSC, marker, origin, stemness, therapy

Background: Cleft lip is a congenital birth defect caused by many proteins. Transforming growth factor (TGF)-β1, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated protein kinase (ERK)-1 are proteins which regulate proliferation and apoptosis role during intrauterine period. This study aimed to observe the expression of these proteins in cleft affected tissue of the lip.Materials and Methods: A descriptive study by examining the TGF-β1, p38 MAPK, and ERK-1 immunohistochemical expression of cleft affected tissue of the lip was conducted. Subjects were patients that were participating for the social event held by Plastic Surgery Department, Faculty of Medicine, Univesitas Brawijaya, on December 3-12, 2012 in Nusa Tenggara Timur. Excess lip mucosa (waste tissue) during the operation were stored in 10% formalin then stained by immunohistochemistry for TGF-β1, p38 MAPK, and ERK-1. We counted the average protein expression under the light microscope with 1000x magnification for 20 different fields of view, randomly.Results: Paraffin blocks from 30 subjects were selected. The mean p38 MAPK expression was found to be highest, with the average of 8 per field of view; followed by the mean TGF-β1 expression, with the average of 5 per field of view; and the mean ERK-1 expression was found to be the lowest, with the average of 2 per field of view. Conclusion: Expression of p38 MAPK and TGF-β1 are higher than ERK-1, suggesting that p38 MAPK is in the same signalling pathway as TGF-β1, while ERK-1 is lower, as its role as anti-apoptotic. This is consistent with several previous studies showing that all proteins took part in the development of cleft lip or craniofacial development. Further study needs to be conducted to determine which protein plays the bigger role.Keywords: cleft lip, TGF-β1, p38 MAPK, ERK-1

Background: Glutathione (GSH) is a principle thiol-containing tripeptide (cysteine, glutamic acid and glycine) antioxidant against free radicals and other harmful oxidants in cellular defence. The alpha-2-macroglobulin (α2M) is large tetrameric zinc-binding glycoprotein which inhibits proteinases regardless of their specificity and catalytic mechanism.Materials and Methods: The interaction of GSH was analyzed with α2M including the structural and functional alterations in α2M using various biochemical and biophysical methods. UV-visible and fluorescence spectroscopy were used to study the binding of α2M with GSH and Fourier transform infrared (FT-IR) spectroscopy was explored to study the structural change induced in α2M.Results: The results suggest that exposure of α2M to GSH decreases the antiproteolytic potential as suggested by the amidase assay. The UV-spectroscopic study showed the formation of α2M-GSH complex and fluorescence analysis showed significant quenching in fluorescence intensity of α2M suggesting GSH binding and structural alteration in the protein. FT-IR spectroscopy was explored to study the structural change induced in α2M which suggest that the secondary structure of α2M changes upon complex formation.Conclusion: Our studies show that interaction of α2M with photoilluminated GSH results in functional and conformational changes of the protein.Keywords: glutathione, GSH, alpha-2-macroglobulin, photo-illumination, ITC, FTIR

Background: Klebsiella pneumoniae is known as an extended spectrum beta (β)-lactamases (ESBLs)-producing bacteria, which produces enzymes that cause resistance to β-lactam antibiotics by degrading β-lactam ring. A solution is needed to prevent the degradation of the β-lactam ring. In this in silico study, combining β-lactam antibiotics with secondary metabolites has the possibility to inhibit the active site of the β-lactamase enzyme. This study aimed to explore the potential of the essential oil of yellow bamboo (Bambusa vulgaris) leaves as inhibitors of β-lactamase. Materials and methods: This research was conducted by simulating molecular docking to determine the interaction of ligands with proteins, pharmacological tests of compounds based on the Lipinski’s rule of five, and ligand toxicity tests with pkCSM. Results: The free bond energy values (∆G) were in the range of -4.3 to -8.0 kcal/mol. The ligands with the best ∆G value were sulfur pentafluoride (-8.0 kcal/mol), squalene (-7.3 kcal/mol), 3-aminodibenzofuran (-7.1 kcal/mol), and 2- monolaurin (-5.5 kcal/mol). Secondary metabolites from the essential oil of B. vulgaris leaves fulfilled Lipinski’s rule of five, so that oral use can be carried out except for squalene and tridecane. Conclusion: Secondary metabolite compounds in the essential oil that have potential as oral drugs based on the Lipinski pharmacological test and the pkCSM toxicity test are dipivaloylmethane, β-ocimene, 2-monolaurin, and undecane. Keywords: β-lactamase, Bambusa vulgaris, essential oil, Klebsiella pneumoniae

Dendritic cells (DC) are antigen-presenting cells between innate and adaptive immune cells and commonly used as immunotherapy. Despite this promising potential, protocols detailing the specifics of the DC production are varied, affecting the potency of dendritic as immunotherapy. There are various factors affecting the production and DC potency, such as sample source, culture period, differentiation and maturation cytokines. Due to the limited number and quality of DC in humans, the monocyte could be isolated and differentiated to mature DC. The purity and viability monocytes shall be maintained to produce a high yield of DC. Negative sorting maintains the potency of DC as a therapeutic agent. Monocytes from umbilical cord blood (UCB) are naïve and can be differentiated to DC easily. Meanwhile, the tumor microenvironment (TME) may inhibit DC maturation from monocyte-derived peripheral blood. Without pro-inflammatory cytokines and a short maturation period, DC remain immature and fails to activate T cells. Long-period culture correlates with decreased DC viability and function. This review outlines several factors which can produce higher cytotoxic T cells and pro-inflammatory cytokines that might help each facility in developing its protocol to ensure the best procedure in DC production. Increasing purity and yield through close and automatic system under GMP production are mandatory to decrease risk of contamination during DC production.Keywords: differentiation cytokines, maturation cytokines, culture period, sample source, isolation technique

Background: Breast carcinoma is the most common malignancy and demands quick and accurate diagnosis and treatment. Precise diagnosis of breast lesions is made using a triple-test approach: clinical, radiological and cytological. However, multiple steps make the process time-consuming and expensive. In developing countries like India, trained and certified radiologists are extremely overburdened. Fine needle aspiration cytology (FNAC) along with clinical examination can fill the gap. This study aims to correlate cytological, radiological and histological findings and measure their relative accuracies. Based on these findings, a new approach will be proposed to address the above shortcomings.Materials and methods: The FNAC was performed on all cases and reported as per Yokohama cytology. The cytological findings were correlated & validated against radiological and histopathological findings respectively. Relative performance of cytological and radiological findings were established using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. A chi-square test for independence between cytological and radiological findings was performed.Results: The sensitivity, specificity, PPV, NPV, and accuracy for cytological findings come out as 97.60, 90.08, 90.37, 97.52, and 93.75, respectively. Meanwhile, the Radiological findings come out as 96.61, 82.20, 84.44, 96.04, and 89.41, respectively. The chi-square test demonstrates strong interdependence between cytological and radiological findings.Conclusion: FNAC is more accurate, quicker, and cheaper than radiological tests. Hence, FNAC based on the Yokohama system, along with clinical observations, can be used as a primary diagnosis tool in developing countries with limited health resources without making significant compromises on incorrect treatment. If needed, radiology and histopathology can be used for precise diagnosis and treatment.Keywords: FNAC, cytology, breast lesions, Yokohama, radiology, histopathology

Background: Resveratrol (RSV) is a polyphenol with potent antioxidant activity and is abundant in fruits. There has been a lot of scientific evidence regarding the anti-aging effect of RSV. Aging can be induced by UV-B (photoaging) due to the production of reactive oxygen species (ROS) and oxidative stress. This study aimed to test the anti-photoaging activity of RSV on UV-B -induced Caenorhabditis elegans.Materials and methods: C. elegans was cultured at 20˚C in nematode growth medium (NGM) and was subjected to various concentrations of RSV and UV-B. The UV-B light exposure was given on day 0 post-synchronization at a dose of 100 J/m2 using a UV cross-linker. The health span (indicated by pharyngeal pumping rate) and lifespan of worms were observed. The quantification of collagen was performed using a Sircol Collagen assay kit. The mRNA expression level of gcs-1, col-19, hus-1, cep-1, egl-1, and ced-13 was examined by qRT-PCR. Results: UV-B reduced pharyngeal pumping rate, shortened the lifespan, decreased collagen, and increased the expression of apoptosis-related genes (hus-1, cep-1, egl-1, and ced-13). RSV ameliorated these aging phenotypes induced by UV-B. Anti-aging activities of RSV were not observed in the skn-1 loss-of-function strain (VC1772, skn-1(ok2315)), indicating the critical involvement of skn-1 in the mechanism of action of RSV. The activation of skn-1 was shown by elevated skn-1 target gene that play role in glutathione biosynthesis called gcs-1.Conclusion: RSV prevents accelerated aging due to UV-B in C. elegans by enforcing skn-1 signaling pathway and its downstream gcs-1 gene expression.   Keywords: anti-aging, resveratrol, oxidative stress, UV-B

Heart disease is the leading cause of death worldwide. Within decades a limited process of cardiac cell regeneration was under observation. Embryonic stem cell (ESC) shows great potential for cell and tissue regeneration. Studies indicate that ESC has the potential to enhance myocardial perfusion and/or contractile performance in ischemic myocardium. However there is still challenge to evaluate the issues of teratoma. Then induced pluripotent stem cell was invented by introducing four transcriptional factors (Oct4, Sox2, Klf4, c-Myc). iPSC was created from murine fibroblast and then differentiated into cardiomyocyte. Reprogramming the adult cell could be performed in full, partial or direct reprogramming. Several studies add the significance by reprogramming the cells through more efficient techniques. However several limitations are still remained.Keywords: cardiomyocyte, reprogramming, iPSC, fibroblast

Background: Survivin, a member of the inhibitor of apoptosis protein family, has been associated with protection from cell apoptosis and regulation of mitosis. Phosphorylated-Survivin at Ser81 was reported to provide cytoprotection against tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in L929 cells by inducing a backloop activation of phosphatidylinositol 3-kinase (PI3K). Therefore Akt as a possible substrate of PI3K was investigated.Methods: L929 cells were pretreated with/without 50 μM LY294002 or 10 μM Perifosine, and infected with viral particle of Survivin, anti sense of Survivin, Ser81Ala mutated Survivin or vector only. Cells were then harvested, lysed and subjected to immunoblot assay to detect Akt, phosphorylated Akt (Ser473), mammalian target of rapamycin (mTOR), phosphorylated-mTOR (Ser2448).Results: Survivin induced Akt and mTOR phosphorylations in a viral particle concentration dependent manner. Pretreatment of LY294002 or Perifosine prior to Survivin infection, attenuated Akt or mTOR phosphorylations, respectively. Low Akt or mTOR phosphorylations were observed when L929 cells were infected with Ser81Ala mutated Survivin.Conclusion: Ser81 phosphorylation site of Survivin played an important role in activating Survivin/PKA/PI3K/Akt/mTOR signaling pathway.Keywords: survivin, Ser81, Akt, mTOR, LY294002, perifosine

Background: Plant-phenolics and flavonoids, including gallic acid, quercetin and rutin, are considered as safe inhibitors for α-glucosidase. This study aimed to compare antioxidant and α-glucosidase inhibitory activities of gallic acid (GA), quercetin (QUE) and rutin (RUT).Materials and Methods: Pure compounds of GA, QUE, and RUT were used. Their antioxidant and inhibitory activity on α-glucosidase were investigated spectroscopically, including their kinetic analysis and interaction mechanism by docking simulation.Results: All the tested compounds (GA, QUE, and RUT) showed good antioxidant activity better than the standards ascorbic acid (AA) and butylated hydroxytoluene (BHT), with QUE showing the highest antioxidant activity based on 2,2-diphenyl1-picrylhydrazyl (DPPH) radical scavenging activity. Based on their reducing properties, the activities of the compounds follow the following order: AA > GA > BHT > QUE > RUT. Both GA and RUT induced a competitive type of inhibition, with activities stronger than acarbose (IC50 = 823 μg/mL), whereas QUE inhibited in a mixed type manner. The IC50 of GA, QUE, and RUT were 220.12, 65.52, and 224.55 μg/mL respectively. The results obtained from molecular docking indicate that all compounds have affinity in the active site pocket of α-glucosidase, with the hydrogen bond being the major force involved in each compound binding to the enzyme.Conclusion: In conclusion, QUE has better antioxidant and α-glucosidase inhibitory activity than GA and RUT. This work provides insights into the interactions between GA, QUE, and RUT and α-glucosidase.Keywords: docking, gallic acid, α-glucosidase, rutin, quercetin

Background: Skin-aging is a progressive changes in the skin combine with cumulative extrinsic factors which are mostly caused by free radicals caused by exposure to lots of free radicals molecules from pollutant, wrongly food intake, or too much sun bathing. These free radicals can be tackled by a treatment using antioxidants. Prevention of aging can be done by escalating antioxidant intake. Protocatechuic acid (PCA) and Ferulic acid (FA) have been known for their scavenging properties on free radicals and antiaging activity. Antioxidant and antiaging activity of both compounds have not been compared comprehensively before. Hence, current study was conducted to compare the potential of PCA and FA for their antioxidant and antiaging activities using various methods.Materials and Methods: Antioxidant analysis of PCA and FA was conducted using H2O2 scavenging assay, 2,2’-azinobis-3-ethylbenzo-thiazoline-6-sulfonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazil (DPPH), and ferric reducing antioxidant power (FRAP). Meanwhile, antiaging activities of PCA and FA were examined using inhibitory activities of tyrosinase, collagenase, elastase, hyaluronidase and tyrosinase.Results: IC50 of scavenging activity of ABTS were 125.18 µg/mL (PCA) and 35.55 µg/mL (FA), inhibition activity of collagenase were 126.16 µg/mL (PCA) and 52.85 µg/mL (FA) and inhibition activity of tyrosinase were 246.42 µg/mL (PCA), 253.58 µg/mL (FA).Conclusion: In conclusion, FA has better ABTS scavenging and collagenase inhibition activities compared to PCA. Meanwhile, PCA has better activity of tyrosinase inhibition than FA.Keywords: antioxidant, antiaging, ferulic acid, protocatechuic acid

Background: The prevalence of post-stroke cognitive impairment (PSCI) ranges from 20-80%. Some studies found that vitamin D deficiency was common in stroke patients, yet the relationship with cognitive performance remains unclear. The study aimed to investigate the relationship between levels of vitamin D and cognitive performance in post-stroke patients.Materials and Methods: This was a cross-sectional study with 20 post-ischemic stroke patients. Vitamin D levels were measured using enzyme-linked fluorescent assay (ELFA). The cognitive performance was assessed by computerized mini-mental state examination (MMSE) and clock drawing test (CDT). The relationship between vitamin D levels and cognitive tests were performed using paired T-test.Results: Vitamin D insufficiency (<30 ng/mL) was experienced by all of the study subjects (100%), with the mean±SD of vitamin D level was 13.75±4.06 ng/mL. More than 70% subjects had cognitive impairment. Based on MMSE, patients with cognitive impairment had lower vitamin D levels, compared with those patients with normal cognition (13±4.38 vs. 16±2.44 ng/mL, p<0.001). In CDT examination, patients with cognitive impairment had slightly higher vitamin D levels, compared with those patients with normal cognition (13.93±4.25 vs. 13.33±3.93 ng/mL, p<0.001).Conclusion: The insufficiency of vitamin D on post-ischemic stroke patients appears to generate a bigger chance of PSCI occurrence. Physicians should be aware of vitamin D status of post-stroke patients, especially in the older population.Keywords: vitamin D levels, post-stroke cognitive impairment, risk factors

Background: Evaluation and identification of HLA antibodies in the recipient’s serum is of utmost importance prior to transplantation and transfusion. HLA typing is a steppingstone in proposing a donor panel. In order to obtain the HLA typing, Polymerase Chain Reaction-Sequence Specific Primers (PCR-SSP) can be performed.Materials and method: This is a preliminary study to determine HLA polymorphism by HLA genotyping in 43 blood donors. DNA from the samples was isolated using commercial kits according to the standard protocol. The DNA then was amplified using PCR-SSP methods and analyzed using the provided set in the kit.Results: This study found that the most frequent HLA-A alleles was HLA-A*24 (41.9%). For HLA-B alleles, the most common was HLA-B*15 (28%). Most frequent HLA-A-B haplotypes was HLA-A*24-B*15 (11.3%). The results from this study concurs with that of previous study. However, some alleles might vary due to difference in study population. Determining HLA-typing is of paramount importance in an ethnically diverse country such as Indonesia. In contrast to homogenous caucassian country, difference in ethnicity might cause platelet refractoriness due to incompatibility. HLA-typing would also guide the diagnostic workup and required treatment strategy for platelet refractoriness.Conclusion: From the HLA typing using PCR-SSP in blood donors in Jakarta, we found that the most frequent alleles were HLA-A*24 and HLA-B*15; and the most frequent haplotypes were HLA-A*24-B*15. This study should be upscaled to include larger population and ethnic groups to obtain complete profile of Indonesian population.Keywords: platelet refractoriness, HLA, donor, PCR-SSP, transfusion medicine

Background: Breast cancer is the second leading cause of cancer death and a health problem worldwide. Secreted mucins are upregulated in ductal adenocarcinoma of the breast, however, the use of mucin as breast cancer biomarker has not been established before. This study aimed to determine the use of mucin level as a potential biomarker for breast cancer diagnosis. Materials and methods: This was a retrospective, cross-section study involving 40 women subjects with breast cancer. Mucin level was examined with a combination of Alcian blue/periodic acid Schiff (AB/PAS) technique applied to each specimen. The results obtained were statistically analyzed using SPSS.Results: Results of neutral mucin detection showed that among breast cancer subjects, 16 cases (40%) were neutral mucin score (+), 23 cases (57.5%) were neutral mucin score (++), and 1 case (2.5%) was neutral mucin score (+++). Meanwhile, 10 cases (25%) were acid mucin negative, 17 cases (42.5%) were acid mucin score (+), 11 cases (27.5%) were acid mucin score (++), and 2 cases (5%) were acid mucin score (+++). The most frequent type of mucin was the combination of acid and neutral mucin (30 cases; 75%) and neutral mucin were 10 cases (25%). Conclusion: Detection of mucin level can be used as an alternative technique for the diagnosis of breast cancer complementary to other types of special stains. Keywords: AB, PAS, breast cancer, histological grade, mucin level

Background: Chronic suppurative otitis media (CSOM) is a persistent inflammatory disease of the middle ear and mastoid cavity caused by pathogenic infection. CSOM has a fairly high incidence in developing countries and is the main cause of acquired hearing loss in children. Tumor necrosis factor alpha (TNF-α) is a significant inflammatory mediator in CSOM. This study aimed to analyze TNF-α levels in ear discharge and blood serum in active phase CSOM caused by Gram-positive and Gram-negative bacteria.Materials and Methods: This research was an analytical observational study with a cross sectional design. Blood serum and ear discharge from CSOM patients were used in this study. Blood serum and ear discharge TNF-α levels were measured using enzyme-linked immunosorbent assay.Results: From 26 CSOM subjects, 13 subjects were infected with Gram-positive bacteria and the 13 others were infected with Gram-negative bacteria. The majority of the subjects were male (53.8%) with an age range from 36-45 years (42.3%). The most common species of bacteria was Pseudomonas aeruginosa. Blood serum and ear discharge TNF-α levels were higher in samples that contained Gram-positive bacteria.Conclusion: TNF-α levels in active phase CSOM caused by Gram-positive bacteria are higher than those which are caused by Gram-negative bacteria.Keywords: chronic suppurative otitis media, TNF-α, gram-positive, gram-negative

Background: Cerebellum is one of the vital components of the brain that will be affected by ischemia-reperfusion (IR) injury. IR injury will increase free radicals, which in turn can trigger apoptosis and cell death. Therefore, this study was conducted to examine the effect of chlorogenic acid administration on apoptosis and the number of cells in the cerebellum of rats with global ischemic transients.Materials and methods: Wistar rats were divided into five groups: sham-operated (C1), IR (C2), IR + 15 mg/kgBW chlorogenic acid (T1), IR + 30 mg/kgBW chlorogenic acid (T2), and IR + 60 mg/kgBW chlorogenic acid (T3). C2, T1, T2, and T3 groups received bilateral common carotid occlusion (BCCO) surgery to induce IR injury. Thirty minutes after BCCO surgery, T1, T2, and T3 rats were administered chlorogenic acid in various doses intraperitoneally. RNA extraction and real-time polymerase chain reaction (PCR) measurements were then performed on NeuN, Bcl2, Bax, caspase 3, as well as on GAPDH as housekeeping genes.Results: There were significant differences in NeuN expressions between groups, with the highest expression shown in C1 followed by T3. Bcl2 expressions were also significantly different between groups, and rats in C1 and T3 showed to be significantly higher compared to C2, while T1 was significantly lower than C1. However, Bax and caspase 3 expressions showed no significant differences.Conclusion: Chlorogenic acid in 60 mg/kgBW dose increases NeuN expression and Bcl2 mRNA expression after transient global ischemia. These increases might correlate with the heightened level of protection against apoptosis in the cerebellum, hence showing its potential in protecting neuron cells.Keywords: transient global ischemia, chlorogenic acid, cerebellum, apoptosis

Cardiac remodeling is a phenotype of heart failure characterized by a molecular, cellular, and interstitial change in the heart, which manifests in the change of size and function of the heart after specific insults with multiple mechanisms. Centella asiatica (CA) and its main bioactive triterpenoid, asiatic acid (AA), pose antioxidant and anti-inflammatory effects. Still, no adequate clinical trials support the potency of CA and AA as anti-cardiac remodeling. Hence, this systematic review aims to provide an in-depth analysis of CA extract and AA in animal studies' prevention or therapy of cardiac remodeling. The search strategies were conducted based on preferred reporting Items for systematic reviews and meta-analysis (PRISMA) protocol through Pubmed, EMBASE, Scopus, and Web of Science using keywords as follows: “Centella asiatica” OR “Asiatic Acid” AND “Cardiac Remodeling” OR “Cardiac Hypertrophy” OR “Cardiac Fibrosis” along with their synonym. The data collected included hemodynamic parameters based on echocardiography, biomolecular tests such as quantitative polymerase chain reaction (qPCR), Western blotting, or biochemistry procedures. The paper quality was assessed using Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias (RoB). The previous selected study has shown that CA and AA might prevent and cure cardiac remodeling by inhibiting various pathways and protein expressions through AMPKα, NOX2/4, PI3K/Akt/mTOR, p70S6K, YAP/TAZ, and IL-1β, IL-6, and IL-18 cytokines. CA and AA, thus, exhibit cardioprotective effects in the animal model, which need to be confirmed in the clinical trials on humans. Keywords: cardiac remodeling, cardiac hypertrophy, cardiac fibrosis, Centella asiatica, asiatic acid

Background: Matrix metalloproteinase-1 (MMP-1) is an enzyme responsible for degrading extracellular matrix (ECM) components, particularly collagen. Overexpression of MMP-1 can accelerate ECM degradation, contributing to various pathological conditions. The most studied polymorphism in the promoter region of the MMP-1 gene is rs1799750, which has been linked to several diseases in previous studies. Androgenetic alopecia (AGA) is a condition characterized by the progressive miniaturization of hair follicles, influenced by androgen signaling and ECM remodeling. This study aimed to investigate the prevalence of MMP-1 gene polymorphism and its potential association with AGA.Materials and methods: This study included 50 subjects diagnosed with AGA and 50 subjects without AGA. All subjects completed a questionnaire that included gender, age, BMI, and ethnicity. DNA was extracted from blood samples for genotyping of the MMP-1 rs1799750 gene. Genotyping was performed using the PCR-RFLP method with AluI as the restriction enzyme. For validation, several samples were sequenced at Apical Scientific Laboratory, Malaysia.Results: Among the 50 subjects with AGA, 9 had the 1G/1G genotype, 26 had the 1G/2G genotype, and 15 had the 2G/2G genotype. Similarly, among the 50 subjects without AGA, 8 had the 1G/1G genotype, 27 had the 1G/2G genotype, and 15 had the 2G/2G genotype. The allele frequencies of 1G and 2G in the AGA group were 0.44 and 0.56, respectively, while in the non-AGA group, they were 0.43 and 0.57, respectively. Chi-square analysis of AGA and MMP-1 genotype yielded a p-value of 0.96, indicating no significant association between AGA and the MMP-1 genotype.Conclusion: In this study, the association between the MMP-1 gene polymorphisms rs1799750 with AGA was not observed.Keywords: Androgenetic Alopecia, matrix metalloproteinase-1, polymorphisms, rs1799750

Stem cell research has been developed and today we can witness some stem cell clinical trials are on going in Indonesia. To meet a successful stem cell treatment, several factors need to be considered, such as cell number. Cell number has been reported to be crucial, and therefore optimal cell number should be achieved. Meanwhile, in some circumstances, cell number is not enough, therefore, cell number should be enriched in an in vitro stem cell culture setting. In an in vitro stem cell culture, besides suitable and sterile equipment, reagents such as culture medium, serum and antibiotics are all important. Although all those criteria are fulfilled, somehow stem cell enrichment cannot be achieved, cell number is still below the target. Modification of stem cell microenvironment should then be an alternative. The addition of growth factors is a part of the strategies to reach a better enrichment. So that, stem cells could later be induced to proliferate at a higher rate. This strategy was then pursued by the scientist involved in herbal medicine. Herbal extracts were now highly investigated due to its potential to induce cell proliferation. Some herbal extracts inducing proliferation and differentiation of stem cell will be shown and described.Keywords: herbal extract, stem cell, progenitor cell, proliferation, differentiation

Background: Several emerging problems of regular hemodialysis (HD) including cardiovascular complication or atherosclerosis formation caused by chronic inflammation. High sensitive C-reactive protein (hs-CRP) and intima-media thickness (IMT) of the carotid artery can be applied as atherosclerosis progressivity marker. This study was designed to investigate the relationship between some inflammatory factors, including hs-CRP, interleukin (IL)-6, oxidized-low-density lipoproteins (LDL), with  IMT  among end-stage renal disease (ESRD) patients. This was the first study in Indonesian population. Materials and Methods: This cross-sectional study was performed on ESRD patients who performed regular HD at Hemodialysis Unit of Dr. Kariadi Hospital and Telogorejo Hospital Semarang between October 2009 and April 2010. This was a preliminary report for the cohort study.Results: Seventy-eight HD subjects were enrolled in this study, with mean age of 49.8 years old. Mean HD duration was 25.5±32.16 months. The mean carotid artery wall thickness was 0.64±0.149 mm. IL-6, hs-CRP, and ox-LDL level were higher in IMT group ≥0.5 mm than IMT group <0.5 mm. There was a significant correlation between hs-CRP (prevalence ratio (PR)=1.3; 95% confidence interval (CI)=1.02-1.7; p-value=0.01) as well as IL-6 (PR=1.5; 95% CI=1.1 -2.0; p-value<0.001) and IMT wall thickness. The oxidized-LDL level was not a significant factor to be associated with IMT. The cut-off value for hs-CRP and IL-6 to predict IMT progressivity was 2.8 mg/L and 2.88 mg/L, respectively.Conclusion: There was a significant correlation between IL-6 and hs-CRP levels and IMT. There was not significant correlation between oxidized LDL and IMT.Keywords: hemodialysis, atherosclerosis, IMT, IL-6, hs-CRP, Oxidized-LDL

Background: Immobilization stress is one method of stress induction on experimental animals. It affects the psychology and physical of experimental animals and is the recommended method for assessing changes in histological structure damage. The purpose of research was to analyze the effect of immobilization stress on gastric mucosal in mice.Materials and Methods: This research was experimental with post-test-only control group design. Twenty white mice (Mus musculus) male Swiss Webster strains were used in this study and divided into 4 groups: control, immobilization stress 14 days, immobilization stress 21 days, immobilization stress 28 days. Mice were given immobilization stress using 50 cc syringes for 2 hours every day for 14 days, 21 days and 28 days. Gastric mucosal damage in mice was analyzed under a microscope with of 10 fields of view in each sample. Data were analyzed using the Kruskal Wallis test and Mann Whitney test.Results: Gastric mucosal damage score were 0 in control, 1.42±0.265 in 14 days, 1.82±0.265 in 21 days, and 2.54±0.05 in 28 days. There was significant difference between each group (p<0.05), while the greatest damage was found in the 28 days group.Conclusion: These result indicated that immobilization stress caused gastric mucosal damage and the degree of damage is in accordance with duration of stress.Keywords: gastric mucosal, immobilization, stress

Background: The antipyretic effect of intravenous versus oral paracetamol is not well known. This study was aimed to compare the antipyretic effect of intravenous and oral paracetamol therapy to reduce fever.Materials and Methods: This was an open-label randomized clinical trial study. The subjects were children who presented to Pediatric Ward and Emergency of Haji Adam Malik Hospital, aged from 2 months to 18 years old, with axillary temperature ≥38.0ºC. Subjects were divided into two groups, group 1 received 15 mg/kg paracetamol intravenous and group 2 received the same dose of paracetamol but given through intravenous. The temperature reduction was analyzed by ANOVA, and the change in temperature was recorded at 0, 15, 30, 60, 120, and 180 minutes after drug administration.Results: In the first group, the mean temperature was decreased (p<0.001) from 15 to 180 minutes after the administration of paracetamol. Nausea was documented as the adverse effect for both oral and intravenous administration groups.Conclusion: The administration of 15 mg/kg paracetamol, either though intravenous or oral, have similar effect in reducing fever in children. Paracetamol therapy though intravenous route can be given if it cannot be given orally.Keywords: antipyretic, pediatrics, fever, intravenous, oral, paracetamol

Intrauterine Growth Restriction (IUGR) incidence in Indonesia ranks in the top 10 of the highest in Asia. It is the main perinatal death cause. IUGR also impairs fetal neurodevelopment, which can affect the development of children until later ages. Lack of 11β-hydroxysteroid dehydrogenase type-2 (11β-HSD2) enzyme is influenced by changes in the coding gene, HSD11B2, one of IUGR's causes. The main diagnostic method of IUGR at this time is by using Doppler ultrasound. However, Doppler ultrasound has several limitations as many cases are not detected. Its clinical predictive value in various women is poor, as Doppler ultrasound is not recommended for use in the first trimester, detection of abnormalities in the second trimester seems to be too late for helpful interventions. The study aim is to present an overview concerning HSD11B2 gene alteration in an non-invasive prenatal testing (NIPT) as a possible diagnostic parameter for early detection in IUGR infants. This literature review is based on selected articles and studies taken from the Pubmed, Proquest, and EBSCO databases. A total of 4 studies reported the tendency for DNA methylation and decreased expression of the HSD11B2 gene in IUGR cases. Changes in the HSD11B2 gene have the potential to become a diagnostic parameter in the early detection of infants with IUGR. Further study and investigation of this possibility are needed.Keywords: intrauterine growth restriction, HSD11B2, early detection, diagnostic, non-invasive prenatal testing

Background: High mutation rates in HIV-1 could affect the accuracy of diagnostic tests. Therefore, recombinant antigen that has an immunodominant and conserved region from HIV-1 need to be developed to detect HIV-1 infection in Indonesia.Materials and methods: The recombinant antigens comprise of Gag (p24), Pol and Env (gp41). Each antigens was expressed in the Escherichia coli expression system and purified using Ni-NTA chromatography. The reactivity of purified antigen against HIV antibodies was tested against a group of 50 HIV-positive plasma samples and 45 HIV-negative plasma samples in a recombinant immunoblot assay (RIBA) platform test. Moreover, 21 of 50 HIV-positive samples and 3 of 45 HIV-negative samples were also tested using HIV blot 2.2 to compare RIBA with a commercial western blot kit. Ten HBV-positive and 10 HCV-positive plasma samples were used to check cross-reactivity with HIV recombinant proteins in RIBA.Results: All HIV-positive samples (100%) tested with RIBA were reactive towards Gag (p24), Pol, Env (gp41). Otherwise, 3 of 21 HIV-positive samples assayed with HIV blot 2.2 were not reactive to Pol protein. All HIV-negative samples tested with RIBA and 3 HIV-negative samples tested with HIV blot 2.2 did not produce any bands of HIV antigens. Few HBV and HCV samples showed reactivity towards HIV recombinant proteins.Conclusion: Each recombinant protein, Gag (p24), Pol, Env (gp41), could be expressed and purified, as well as had reactivity to HIV-positive samples in RIBA test. Therefore, RIBA can be used as a diagnostic test to detect HIV-1 infection in Indonesia.Keywords: diagnostic, HIV-1, immunodominant, recombinant immunoblot assay (RIBA)

Background: Diabetic kidney disease (DKD) is one of diabetes mellitus microvascular complications. Engulfment and cell motility 1 (ELMO1) protein interacts with dedicator of cytokinesis 180 (DOCK180) and cyclooxygenase (COX)-2, which affects gene expression in extracellular matrix (ECM) and causes glomerular damage in several mechanisms, such as ECM accumulation and renal tubules thickening. Single nucleotide polymorphism (SNP) rs741301 is one of the ELMO1 genetic polymorphisms involved in DKD. The aim of this study was to evaluate the association between ELMO1 rs741301 polymorphism and DKD in type 2 diabetes mellitus (T2DM) among Balinese.Materials and methods: This study was an observational analytical study with case-control method. Subjects were divided into control and case groups comprising 40 subjects each. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) of DNA from T2DM patients were performed to detect the polymorphism in ELMO1 rs741301. Genotype and allele distribution obtained from this study was analyzed by chi-square (χ2) test and Hardy-Weinberg equilibrium law (p<0.05; CI: 95%).Results: There was no significant difference between genotype or allele distribution of ELMO1 rs741301 with DKD incidence. Genotype AA against GG had odds ratio (OR) of 0.793 (p=0.814), AG against GG had OR of 0.602 (p=0.674), and A allele against G allele had OR of 0.761 (p=0.509).Conclusion: There is no significant relationship between ELMO1 rs741301 polymorphism and DKD in T2DM patients among Balinese.Keywords: ELMO1 gene, diabetic kidney disease, polymorphism

The medical biotechnology community has undertaken significant endeavors to gain a comprehensive understanding of SARS-CoV-2’s biology and pathogenesis mechanisms. Omics approaches and technologies have been widely employed in the fight against SARS-CoV-2. Since the onset of the virus outbreak, researchers have demonstrated how recent omics and bioinformatics technological advancements have contributed to the diagnosis, vaccine development, treatment, and control of disease transmission. Studies conducted since the outbreak have been collected and summarized, with a focus on bioinformatics approaches and their contribution to controlling this pandemic. Developments and advanced omics technology in connection to the COVID-19 pandemic have been analyzed. The multi-omics technology, which offers various strategies in identifying potential diagnostics, therapeutics, studies of variants of concern, and drug repurposing approaches, has been assessed. Pandemic response has seen the application of multi-omics and pan-genomics approaches, including genomics, metabolomics, transcriptomics, proteomics, epigenomics, clustered regularly interspaced short palindromic repeats (CRISPR) technology, host-pathogen interactions, artificial intelligence, and machine learning in various research areas. Additionally, bioinformatics and mathematical modeling have played a significant role in disease control. The use of smart technologies to control virus transmission and predict patients’ health conditions and treatment outcomes has also been crucial. Transcriptome analysis has emerged as a major application, contributing to the generation of new knowledge on viral sequences and intracellular signaling pathways that regulate viral infection and pathogenesis mechanisms. The sequencing of the virus has paved the way for the use of omics technologies and an integrative technique in combating the pandemic. In general, the advancement of omics technology during this pandemic has been fascinating and has contributed a significant role to the science of health biotechnology in general and omics and bioinformatics in particular.Keywords: bioinformatics, coronavirus, COVID-19, omics, SARS COV-2

Background: Early onset preeclampsia (PE) is considered a fetal disorder that is associated with placental dysfunction. While late onset preeclampsia is considered a maternal disorder that associated with a normal placenta. An imbalance of angiogenesis factors, namely soluble Fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) is not only a strong predictor of PE but can also be a predictor of poor outcomes or adverse complications of PE. This study was conducted to analyze the difference between angiogenesis factor sFlt-1 and PlGF in maternal serum between patients with early and late onset PE. Material and Methods: This was a cross-sectional study involving pregnant women with PE who were ≥18 years old and gestational age >20 weeks had singleton pregnancies. Subjects who had a major morphological abnormality of a fetus diagnosed with USG and chromosomal abnormality of the fetus were be excluded. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured using a digital blood pressure measuring instrument. sFlt-1 and PlGF levels were measured using enzyme linked immunosorbent assay (ELISA). Result: This study showed the level of maternal serum sFlt-1 was 7522.95 pg/mL and the level of maternal serum PlGF was 222.25 pg/mL. There was a difference between sflt-1, PlGF, and the sflt-1/PlGF ratio (p=0.00; p=0.00; p=0.00) in early and late onset of PE where at early onset PE was found higher sflt-1 and late-onset PE had lower PlGF and higher sflt-1/PlGF ratio. Conclusion: There are differences in sFlt-1, PlGF, and sFlt-1/PlGF in early and late onset PE, as higher sflt-1 is found in early onset preeclampsia, while lower PlGF and higher sflt-1/PlGF ratio are found in late onset preeclampsia.Keywords: early onset, late onset, preeclampsia, maternal angiogenesis factor, Flt-1, PlGF

Background: The optimal rate for fluid bolus administration in septic shock remains a critical and unresolved question. Rapid bolus administration is commonly practiced but has been linked to elevated levels of atrial natriuretic peptide (ANP), matrix metalloproteinase-2 (MMP-2), and syndecan-1 shedding, potentially exacerbating endothelial glycocalyx damage and increasing vascular permeability. However, the physiological and clinical implications of slower bolus rates have not been thoroughly investigated. This study was conducted to identify safer fluid management practices and improve patient outcomes in septic shock.Materials and methods: A randomized post-test-only control group design was employed, involving 36 male New Zealand rabbits with lipopolysaccharide-induced septic shock. The treatment group received 0.9% NaCl boluses (20 mL/kg body weight) over 20 minutes per bolus (slow bolus), while the control group received the same volume over 5 minutes per bolus (rapid bolus). ANP, MMP-2, and syndecan-1 levels were measured using ELISA 10-15 minutes post-intervention.Results: The median ANP levels in the treatment group (92.86 ng/mL) were significantly lower (p<0.05) than those in the control group (367.32 ng/mL). The mean MMP-2 levels in the treatment group (10.26 ng/dL) were lower than those in the control group (11.43 ng/dL). The median levels of syndecan-1 were also lower in the treatment group (4.31 ng/mL) compared to the control group (5.94 ng/mL).Conclusion: Slow fluid boluses appear to mitigate endothelial damage by reducing ANP, MMP-2, and syndecan-1 shedding. These findings suggest that slower infusion rates may offer a protective advantage in fluid resuscitation, paving the way for updated clinical guidelines.Keywords: fluid bolus, ANP, MMP-2, syndecan-1

Reciprocal interaction between oral ectodermal epithelial cells and mesenchymal stem cells (MSCs)-derived from the cranial neural crest starts the teeth development. The role of dental MSCs continues throughout life. The dental MSCs do not only play a role in tooth development but also in tooth homeostasis and repair. There are many kinds of dental MSCs, such as dental pulp stem cell (DPSC), stem cell from apical papilla (SCAP), stem cell from exfoliated deciduous teeth (SHED), periodontal ligament stem cell (PDLSC) and stem cell from dental follicle (DFSC). Aligned with the proposed criteria by the International Society for Cellular Therapy (ISCT), dental MSCs are adherent cells and like other MSCs, dental tissue MSCs are capable of giving rise to cell lineages such as osteo/odontogenic, adipogenic, and neurogenic. Various surface antigens of dental MSCs were reported, however, mostly typical antigens suggested by ISCT were fulfilled. Surface antigens from each dental MSCs (DPSC, SCAP, SHED, PDLSC and DFSC) are being described in the current report.Keywords: dental stem cells, mesenchymal stem cells, tissue regeneration, DPSC, SCAP, SHED, PDLSC, DFSC

Background: A pressure ulcer (PU) is localized injury to the skin and/or underlying tissue usually over a bony prominence, as a result of pressure, or pressure in combination with sharp surface. Several studies have found that PU is also a common problem in the pediatric population. Infection at PU sites is the most common complication, where PU can host resistant microorganisms and can turn into a local infection that is a source of bacteremia in hospital patients. This study aims to determine the most common bacteria and antimicrobial susceptibility at the site of PU in pediatric patients that serve as baseline data in Haji Adam Malik Hospital.Materials and Methods: A cross-sectional study was carried out in July-December 2017, involving 30 PU pediatric patients. For each subject, swab from ulcers were cultured in microbial laboratory to determine the microbial pattern and antimicrobial susceptibility.Results: The most common age group was 0-3 (53.3%), the highest gender was male (60%), the most common type was type 2 (46.7%), the main location was occipital (30%) and the most common undelying diseases were hydrocephalus (16.6%). The most common microbial pattern in PU pediatric patients is Acinetobacter baumannii (40%). The highest sensitivity is vancomycine for gram positive bacteria and amikacine for gram negative bacteria.Conclusion: The most common microbial pattern in PU pediatric patients in Haji Adam Malik Hospital is Acinetobacter baumannii (40%). The highest sensitivity is vancomycine for gram positive bacteria and amikacine for gram negative bacteria.Keywords: pressure ulcer, pediatric, microbial pattern, antimicrobial susceptibility

Background: Skin aging is a condition where skin is unable to retain both its physiological and structural integrity. Plants is the main source of phtytochemicals compound with wide range of biological activities. Through the efforts of ongoing scientific researches, an increasing number of plant extracts and phytochemicals have been showed promising result as anti-aging agent. Snake fruit (Salacca zalacca (Gaert.) Voss) is tropical plant belongs to the palm tree family (Arecaceae) that served as important crop in Indonesia. Despite its utilization, the phytochemical compound available in snake fruit, especially its peel have not been well documented. Present study aimed to elucidate the phytochemical constituent of snake fruit peel and its anti-aging potency.Materials and Methods: Snake fruit peel extract (SPE) was subjected to qualitative phytochemical assay, high performance liquid chromatography, and molecular docking towards protein related in skin aging.Results: The screening showed SPE contained phytochemical compound belong to flavonoid, tannin, phenol, triterpenoid, saponin and alkaloid. Thus, based on the analysis only chlorogenic acid was present in SPE whilst rutin and caffeic acid were not detected. The SPE was contained chlorogenic acid around 1.074 mg/g dry weight. Chlorogenic acid had the high binding affinity towards matrix metalloproteinase (MMP)-1 (-9.4 kcal/mol).Conclusion: Current findings may provide scientific evidence for possible usage of SPE and its compounds as antioxidant and anti-aging agent.Keywords: Salacca zalacca, phytochemical compound, high performance liquid chromatography, anti-aging

Background: Obesity contributes to the increased risk of chronic kidney and systemic inflammation. This condition can occur in obese adolescents. Most researches of cystatin-C (cys-C) and adiponectin have been carried out in adult and children subjects. The purpose of this research is to determine differences in serum cys-C and adiponectin levels between obese and normoweight adolescents and their correlation with blood pressure and obesity parameters.Materials and Methods: Twenty-eight obese adolescents and 22 normoweight adolescents aged 15-18 years old participated in this research. After the measurement of blood pressure and obesity parameters, we examined serum cys-C levels as a biomarker for decreased early stage renal function and adiponectin, an antiinflammatory adipokine. Estimated glomerular filtration rate (eGFR) based on serum cys-C is calculated using the eGFR-Chronic Kidney Disease Epidemiology Collaboration (eGFR-CKD EPI cys-C equation formula). Results: Cys-C levels in obese adolescents were higher than normoweight adolescents. In contrast, serum adiponectin levels in obese adolescents were lower than for normoweight adolescents. Interestingly, eGFR based on serum cys-C showed no difference, although eGFR in obese adolescents was lower than normoweight adolescent. Serum cys-C was positively correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) and waist circumference (WC). Serum adiponectin was negatively correlated with SBP, DBP, BMI and WC. SBP is a predictor factor for the increase in serum cys-C and BMI is a predictor factor in the decrease in serum adiponectin levels. Conclusion: There is a decline in early stage kidney function and inflammation in obese adolescents as evidenced by increased serum cyst-C levels and decreased serum adiponectin levels. These two biomarkers correlate with blood pressure, BMI and WC and play a role in the pathomechanism of early stage impairment of kidney function and inflammation in obese adolescents.Keywords: adiponectin, body mass index, cystatin-C, early stage renal diseases, inflammation, systolic blood pressure

Background: Retinal artery caliber (RAC) is narrower in human immunodeficiency virus (HIV)-infected patients beginning antiretroviral therapy (ART). We aimed to assess associations between variations in genes encoding inflammatory mediators and natural killer receptors and retinal artery caliber (RAC) in HIV patients beginning ART.Materials and Methods: Seventy-nine HIV positive patients beginning ART with less than 200 cluster of differentiation (CD) 4 T-cells/μL were recruited. Examinations were performed before ART (V0) and at months 3, 6 and 12 (V3, V6, V12). The study was approved by ethics committees and informed consent was obtained from each subject.Results: Right and left RAC of the HIV patients were narrower than healthy controls (p=0.016 for right RAC) and narrowed further on ART, but demographic associations with the right and left RAC were not identical. Here we show that polymorphisms in genes encoding NK receptors or TNF activity had no significant impact, but right RAC was associated with carriage of allele 2 at IL1A+4845 (p=0.037 after 12 months on ART).Conclusion: Overall the paradoxical reduction in the RAC in HIV patients responding to ART was not modified by genotypes known to affect NK cell function or TNF responses, but IL1A genotype may modify the decline in the right RAC.Keywords: anti-retroviral therapy, CMV, HIV, IL1A, retinal artery caliber

Background: In 2017, about 1.2 million people died because of Chronic Kidney Disease (CKD). Patients with CKD are known to have increased levels of oxidative stress which leads to decrease in NO production. NO is a highly reactive signaling molecule and a major determinant of vascular homeostasis. Thus, the decreased NO can be a risk factor for the development of atherosclerosis and increased cardiovascular risk. Meanwhile, Malondialdehyde (MDA) is known as excellent biomarker for oxidative stress. This study aims to determine the correlation of serum total nitric oxide (NO) and urine MDA levels in non-hemodialysis CKD patients.Materials and Methods: This study was an observational clinical study with a cross sectional design. Fourty-nine CKD subjects were selected by consecutive sampling. The samples for laboratory tests were collected from urine. MDA concentration was measured using the High-Performance Liquid Chromatography (HPLC) kit. NO concentration was measured with Griess reaction method and Total Nitric Oxide Parameter kit. The data were analyzed using the Statistic Package for Social Science (SPPS) software version 16.Results: The data showed significant negative correlations between MDA with NO (r=-0.294; p=0.041).Conclusion: There was a correlation between serum total NO and urine MDA levels in non-hemodialysis CKD patients.Keywords: chronic kidney disease, malondialdehyde, nitric oxide, non-hemodialysis