Study of the Molecular Dynamics Stability in the Inhibitory Interaction of Tenofovir Disoproxil Fumarate against CTLA-4 in Chronic Hepatitis B Patients.

Background: Tenofovir disoproxil fumarate (TDF) is a first-line nucleotide analog (NA) drug for hepatitis B therapy. Long-term NA therapy increases peripheral T cell levels to enhance antiviral response, while CTLA-4 inhibits the activation. Objective: This study analyzed the interaction between TDF and CTLA-4 through molecular docking. Methods: Target protein and ligand data mining were performed, and proteins were prepared by removing water molecules in the Discovery Studio 2019 software. The energy minimization was performed on ligands using Pyrx v.0.9.8 software. Protein-ligand docking was performed using Autodock Vina integrated with Pyrx v.09.8. Meanwhile, the docking of proteins was accomplished using the Haddock server. The BioVia Discovery Studio 2019 software visualized the interaction between the compound and the docked protein. Molecular dynamics simulations were carried out using the YASARA Dynamic program developed by Biosciences GmbH. Results: TDF ligand has good and stable inhibitory activity against the CTLA-4/B7-1 and CTLA4/B7-2 complexes. TDF docking has been shown to initiate conformational changes, indicating the ligand's inhibitory activity. The significant conformational changes based on superimposition results were shown by the CTLA-4/TDF/B7-2 and CTLA-4/B7-1/TDF complexes. TDF in all ligands undergoes bonding and displacement of binding sites. Conclusion: Treatment with TDF was predicted to have inhibitory activity against CTLA-4, especially in its complex form with B7-1 and B7-2.

Anti Inflammatory Action of Allium Sativum Ethanol Extract to Prevent Lung Damage in Smoker Rat Model.

Background: Smoking is the leading cause of death in worldwide and is known as one of the risk factors in the development and pathogenesis of several diseases and most are respiratory and cardiovascular diseases. Secondhand smoke (SHS) exposure is associated with negative health consequences including respiratory tract infection, asthma, and cancer. One of the pathogenesis that has known to cause these diseases is inflammation. Garlic (Allium sativum) is a medicinal herb that contains Allicin and other active constituents that are known to have anti-inflammatory ability by suppressing the expression and production of proinflammatory cytokines that will cause inflammation. Objective: The aim of this study is; to analyze the anti-inflammatory action of Allium sativum ethanol extract to prevent lung damage in the smoker rat model. Methods: This is a case-control study with five groups of rats each group contains of three rats. The five groups were negative control (KN), 10 days (10d) smoker (K1), 20 days (20d) smoker (K2), 20d smoker treated with Allium sativum for 10 days (K3) and 20d smoker treated with Allium sativum for 20 days (K4). After 20 days all animals were sacrificed and histological preparation of lung organs was observed under a microscope with 100 dan 400 times magnification and then captured by photomicrograph for analyzed. Results: There were improvements in lung structure both in group K3 and K4 . there was a decrease of leucocytes and inflammatory cells infiltration that covered almost all alveolar surface to 10-20% surface area and the dilated alveoli decrease from more than 50% to less than 30% area. The bronchus was clean in both two groups compared to the groups that were not treated with Allium sativum. Conclusion: This study shows that Allium sativum ethanol extract has the ability to prevent lung damage in the smoker rat model.

Association Between Serum Cytotoxic T Lymphocyte Antigen (CTLA)-4 Level and Disease Progression in Patients With Chronic Hepatitis B.

Backgroud: Immune impairment, marked by increased expression of cytotoxic T lymphocyte antigen (CTLA)-4, promotes the disease progression of chronic hepatitis B. Objective: This study aimed to determine the association between serum CTLA-4 level and disease progression in patients with chronic hepatitis B. Methods: A cross-sectional study was conducted at Haji Adam Malik General Hospital Medan, Indonesia between October 2021 to September 2022. A total of 150 participants were enrolled. Patients aged 18 years or older with evidence of chronic hepatitis B, HBV-related liver cirrhosis, and HBV-related hepatocellular carcinoma (HCC) were enrolled. Exclusion criteria were history of chronic hepatotoxic drug consumption, underlying liver abnormalities other than HBV infection, and liver injury due to metastasized malignancy from other sites. Serum CTLA-4 level was determined from serum using human CTLA-4 enzyme linked immunosorbent assay kit. Results: Most participants were males and aged between 40 and 60 years. Serum CTLA-4 level was positively associated with chronic hepatitis B progression (P<0.001). Serum CTLA-4 level was negatively correlated with serum platelet (P<0.001) and albumin levels (P<0.001) but positively correlated with serum ALT (P=0.045) and total bilirubin levels (P<0.001). Conclusions: Serum CTLA-4 level is associated with disease progression in patients with chronic hepatitis B.

Use of saliva as an alternative diagnostic method for diagnosis of COVID-19.

Background: Mass population testing has been recommended to contain the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, the use of nasopharyngeal swab specimens has caused many logistic challenges. This study investigated the sensitivity and specificity of saliva as a non-invasively-obtained specimen for molecular detection of SARS-CoV-2 RNA. Methods: In total, 153 patients with confirmed coronavirus disease 2019 (COVID-19) who had been admitted to the regional referral hospital or who self-isolated at home were included in this study. Nasopharyngeal swab specimens and saliva samples were collected on the same day, and were tested for SARS-CoV-2 infection using reverse transcriptase polymerase chain reaction. Results: The sensitivity and specificity of saliva samples were 81.5% and 76.4%, respectively, in cases that had been confirmed as COVID-19 using nasopharyngeal swab samples. Positive predictive values and negative predictive values were 92.3% and 54.1%, respectively. The highest detection rates were found among samples collected 4-7 days since symptom onset. Conclusion: Saliva samples showed comparable performance to nasopharyngeal swab specimens for the diagnosis of COVID-19 in adults. The performance of saliva as a diagnostic specimen for COVID-19 testing is particularly significant during the first week of symptoms.

Serum homocysteine level and severity of coronavirus disease-2019 (COVID-19).

INTRODUCTION: Coronavirus disease-2019 (COVID-19) is still a global health problem nowadays. A particular COVID-19 patients develop severe symptoms. Some biomarkers can be used to determine disease severity and improve outcome. Homocysteine is one of the novel biomarkers. The objective of this study is to determine the role of serum homocysteine level in stratifying severity of COVID-19. METHODS: A cross-sectional study was conducted in Medan, Indonesia from May to December 2021. Subjects were obtained using consecutive sampling method. Inclusion criteria was COVID-19 patients aged 18 years or older and willing to participate in the study. Patients with malignancy, chronic kidney disease, thyroid disease, coronary heart disease, and who consume several medications including cholestyramine, metformin, methotrexate, fibrate, and contraceptive pill, were excluded. Data regarding demographic, laboratory, and biomarker were gathered from each subject. Statistical analyses were conducted at 95% confidence interval. RESULTS: A total of 100 patients were enrolled. Most subjects were males (59%) and from Batak ethnicity (64%). Twenty percent subjects had severe COVID-19. The levels of serum high-sensitivity C-reactive protein (hs-CRP), D dimer, homocysteine, and procalcitonin were significantly higher in severe COVID-19 subjects. D dimer had the highest sensitivity (91.7%) and specificity (94.7%) in stratifying severe COVID-19, followed by hs-CRP (91.7% and 85.5%, respectively), homocysteine (87.5% and 78.9%, respectively), and procalcitonin (58.3% and 74.0%, respectively). CONCLUSION: Homocysteine can be used as a biomarker to determine COVID-19 severity.

Effect of Garlic Ethanol Extract Administration on Gluthatione Levels to Prevent Oxidative Stress in Smoker Rat Model.

Background: Sickle Garlic (Allium sativum L.) is known as a spice native to western Asia has a strong antioxidant effect and revealed it functions as an antioxidant by increasing ROS-capture activity, cellular antioxidants, SOD, CAT, and GSH levels in cells. Cigarette smoke is very dangerous because it can cause serious illness and death. Cigarette smoke is a major source of exogenous ROS because its particles are high in free radicals. Smoking is also related to a decrease in the body's natural antioxidant levels. Glutathione (GSH) synthesis and expression were found to increase initially and then decrease after being exposed to cigarette smoke. Objective: The aim of this study is; to analyze effect of garlic ethanol extract administration on gluthatione levels to prevent oxidative stress in smoker rat model. Methods: This was a case-control study with a control group design, with 15 healthy rats (Rattus norvegicus, sp.) divided into three groups, KN untreated animals (control), K1 animals exposed to cigarette smoke for 40 days (smoker), and K2 animals exposed to cigarette smoke for 40 days and treated with Allium sativum 0.1 g per day for 40 days (smoker and Allium sativum L.). After 40 days of treatment, all animals, including the control, were sacrificed with 30 mg/IP ketamine injections, and the blood plasma were taken for examination. Results: there were significant difference in glutathione levels between the treatment groups (K2) with the control group (KN) and the smokers group (K1) (p <0.05). Conclusion: garlic ethanol extract administration can increase gluthatione levels and prevent oxidative stress in smoker rat model.

Association Between Serum Midkine Level and Gastric Precancerous Lesion in Patients with Gastritis.

Background: Gastric cancer is the fifth most common malignancy and the third highest cancer-related mortality worldwide after lung and colorectal cancers. The gastric carcinogenesis is started with precancerous lesion. Prompt diagnosis and management of gastric precancerous lesion may prevent disease progression. Midkine is a growth factor associated with various cancers and proposed as a marker for detecting gastric precancerous lesion. Objective: The aim of the study is to determine the association between serum midkine level and gastric precancerous lesion in patients with gastritis. Methods: A cross sectional study was conducted at Haji Adam Malik general hospital. Subjects were obtained by consecutive sampling. Inclusion criteria were patients aged 18 years or older, diagnosed with gastritis from gastroscopy and histopathology results, and willing to cooperate in the study. Each subjects underwent interview and endoscopic examination. Serum midkine level was determined using enzyme-linked immunosorbent assay (ELISA) method. Chi square, receiver operating characteristic (ROC) curve, and logistic regression tests were applied. Results: A total of 160 subjects were enrolled with 29.4% had gastric precancerous lesion. Serum midkine level was associated with gastric premalignant lesion. Cut off point for serum midkine level was 252 pg/mL with area under the curve of 0.816 (p<0.001). It's sensitivity, specificity, and accuracy in diagnosing gastric precancerous lesion were 74.5%, 71.7%, and 72.5%, respectively. Helicobacter pylori infection, high serum midkine level, heavy alcohol drinker, and family history of gastric cancer were risk factors for gastric precancerous lesion. Conclusion: Serum midkine level is associated with gastric premalignant lesion in patients with gastritis and has good diagnostic values.

Factors affecting HBV DNA suppression in chronic hepatitis B patients treated with tenofovir disoproxil fumarate.

Background: This study aims to determine the factors affecting HBV DNA suppression in chronic hepatitis B patients with tenofovir disoproxil fumarate (TDF). Methods: A case-control was carried out from October 2021 to August 2022 on 182 chronic hepatitis B patients who had TDF therapy regularly for 24 weeks at H. Adam Malik and USU Hospitals in Medan, Indonesia. The history of the samples was obtained, followed by physical examination, and blood collection. CTLA-4 polymorphism examination was carried out using real-time PCR, while the serum CTLA-4 levels were assessed with ELISA. Results: The CTLA-4 -1661G>A polymorphism, genotype GG+AG, increased 1.52 times risk of not achieving HBV DNA suppression to TDF compared to genotype AA (p=0.041). High CTLA-4 levels increased 2.28 times risk, high HBV DNA levels increased 2.09 times risk, low ALT levels increased 1.95 times risk of not achieving HBV DNA suppression (p= 0.009, 0.026, 0.036, respectively). There was no relationship between gender, age, ethnicity, obesity, baseline AST, HBeAg, genotype, liver fibrosis and HBV DNA suppression after 24 weeks of treatment (p>0.05). Conclusions: The levels of CTLA-4, HBV DNA, ALT, and CTLA-4 -1661G>A polymorphism have a potential relationship with the suppression of HBV DNA in chronic hepatitis B patients with TDF.

Association of endothelial nitric oxide synthase gene (G894T) polymorphism and hypertension in diabetic Bataknese patients.

Aim To assess endothelial nitric oxide synthase (eNOS) gene (G894T) polymorphism and nitric oxide (NO) level in hypertensive diabetic Bataknese patients. Methods A hospital-based, case control study (hypertensive and normotensive diabetic patient) was conducted. Genotyping of eNOS gene (G894T) was done using polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP). Nitric oxide was quantified by sandwich enzyme-linked immunosorbent assay (Sandwich ELISA). Results GT polymorphism and T allele were higher in the hypertensive diabetic patients, 37.5% (p=0.6) and 54% (p=0.39), respectively. Nitric oxide level tended to be lower in the hypertensive diabetic patients (88.87µmol/L) comparing to the normotensive (95.42 µmol/L (p=0.54), as well as GT and TT polymorphism type (p=0.75). Conclusion eNOS gene (G894T) polymorphism is not associated with NO level and hypertension in the diabetic Bataknese patients.