Molecular and Cellular Biomedical Sciences (E-Journal)
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The Role of Hypoxia-inducible Factor in Mycobacterium tuberculosis-infected Macrophages
No full textTuberculosis is caused by Mycobacterium tuberculosis infection. During M. tuberculosis infection, there is a decrease in the partial pressure of oxygen in the granuloma microenvironment, which causes the hypoxia-inducible factor (HIF) to become stable. HIF functions as a transcription factor that regulates the expression of genes crucial for metabolic adaptation in hypoxic conditions. Recent research suggests that HIF plays a vital role in infectious and inflammatory conditions. Several studies have demonstrated that HIF signaling can enhance macrophages antimicrobial activity and bactericidal effect against M. tuberculosis, such as increasing macrophage autophagy, enhancing the effects of rifampicin, inhibiting p38 MAPK signaling, enhancing the regulation of effector antimicrobial pathways mediated by human β defensin 2 (hBD2) and vitamin D receptor (VDR), redirecting energy metabolism to glycolysis, and producing various cytokines. All these responses ultimately result in the inhibition of intracellular M. tuberculosis growth. HIF has therapeutic implications, potentially being a new candidate for host-directed therapy as a complement to existing antituberculosis drugs. Understanding the role of HIF in macrophages during M. tuberculosis infection and comprehending the host-pathogen relationship with M. tuberculosis is advantageous for developing future therapies.Keywords: Mycobacterium tuberculosis, macrophages, hypoxia-inducible facto
ACE I/D and A2350G Polymorphisms are Correlated with Body Mass Index, but Not with Body Weight and Essential Hypertension: Study in Javanese Postmenopausal Women
No full textBackground: Genetics was one of the risk factors for essential hypertension (EH). Research on ACE I/D and A2350G polymorphisms associated with risk factors for hypertension in Indonesia has never been done. Therefore, this study was conducted to analyze the relationship between the genotype and alleles of this gene with EH, body weight, and body mass index (BMI) in Javanese postmenopausal women.Materials and methods: This cross-sectional study involved 69 postmenopausal Javanese women according to several criteria related with hypertension risk factors. The data were obtained from the measurement and questionnaire results, along with Towards Health Card Records. The polymerase chain reaction (PCR) genotyping method used was the restriction fragment length polymorphism and allele-specific.Results: The prevalence of hypertension, prehypertension, and normotension in Javanese postmenopausal women were 0.246, 0.13, and 0.623, respectively. The frequency of BMI classification as underweight, normal, overweight, or obese were 0.029, 0.42, 0.261, and 0.29, respectively. The ACE I/D and A2350G polymorphism variant genotypes and frequencies found were II (0.464), ID (0.522), DD (0.014), and AA (1). Meanwhile, the alleles and their frequencies at ACE I/D gene polymorphism were I (0.725) and D (0.275). The II and ID genotype was mostly found in normotension subjects. The DD genotype was only available in hypertension subjects. There was no association between genotypes and alleles of ACE I/D, hypertension, body weight, and BMI classification (p>0.05). There was an association between these genotypes, alleles, and BMI (p<0.05).Conclusion: ACE I/D polymorphism is susceptible for BMI in Javanese postmenopausal women.Keywords: Javanese postmenopausal, essential hypertension, ACE I/D, ACE A2350
Virtual Screening of Indonesian Herbal Compounds with Neuraminidase Inhibitor Activity against N2 Influenza Virus Protein: An in silico Study
No full textBackground: Neuraminidase inhibitor (NAI) is one of anti-influenza drugs recommended for use by the World Health Organization (WHO). However, after treatment with NAI drugs in human, resistance to influenza antiviral drugs is begun to rise. Therefore, identification of compounds from Indonesian herbal plants as natural inhibitors of the influenza virus neuraminidase protein needs to be conducted for the development of new anti-influenza drugs.Materials and methods: The crystal structure of the neuraminidase protein complex used in this study was obtained from the Protein Data Bank (PDB). Structure-based pharmacophore modeling was performed using LigandScout version 4.4.5 software. Indonesian herbal plant compounds were collected from the HerbalDB database. Protein and ligand processing was carried out using Autodock 4.2 software. The 3D interaction visualization was carried out with Autodock software, while 2D interaction visualization was carried out with LigPlot software. To determine the toxicity and drug-likeliness of the ligand, the test ligands that had the best docking results were predicted using SwissADME and AdmetSAR.Results: From the virtual screening results, 24 hits were found, and five compounds had the best binding energy among the 24 tested compounds, these were pollenitin (ΔG=-7.22 kcal/mol), OPC-4:0 (ΔG=-7.11 kcal/mol), 6-hydroxykaempferol (ΔG=-7.08 kcal/mol), 5,8-dihydroxy-7,4'-dimethoxyflavone (ΔG=-7.07 kcal/mol), and 3,5,6,7-tetrahydroxy-4'-methoxyflavone (ΔG=-6.95 kcal/mol). The best five compounds were then chosen for further analysis.Conclusion: OPC-4:0 is found to be the best compound for the NAI based on its binding energy, pharmacokinetics, toxicity, and drug-likeliness. Thus, OPC-4:0 might be a potential candidate as a NAI of HxN2 virus. Keywords: influenza, molecular docking, neuraminidase, resistance, virtual screenin
Potential Anti-Senescence Effect of Extract from Andrographis paniculata Herbal Plant and Its Bioactive Compounds: A Systematic Review
No full textThe 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, senescenc
In silico Investigation on Clopidogrel, Prasugrel and Ticagrelor as Potential Mono Antiplatelet Therapy for Acute Coronary Syndrome
No full textBackground: In acute coronary syndrome (ACS), antiplatelet therapy is crucial for inhibiting platelet aggregation. Dual antiplatelet therapy (DAPT) commonly employs aspirin along with clopidogrel, prasugrel, or ticagrelor. This is well known that aspirin acts as a cyclooxygenase (COX)-1 inhibitor, while clopidogrel, prasugrel, and ticagrelor act as P2Y12 inhibitors. Despite DAPT's proven efficacy in more effectively reducing cardiovascular events in ACS patients, this is associated with an increased risk of bleeding compared to mono antiplatelet therapy (MAPT). To minimize the cost and side effect that might arise from the use of DAPT, this is necessary to assess the potential of MAPT using a P2Y12 inhibitor drug, to understand whether they are capable of binding to both COX-1 and P2Y12. Hence, this study was conducted to identify P2Y12 inhibitor drugs that have the ability to bind to COX-1, allowing them to be proposed as MAPT.Materials and methods: Molecular docking was employed to assess binding affinity, interaction types, amino acid residues, binding distances, and visualizations in both 3D and 2D formats. The applications utilized were BIOVIA Discovery Studio and AutoDock, while the websites utilized were research collaboratory for structural bioinformatics protein data bank (RCSB PDB) and PubChem.Results: In silico findings reveal differences in binding strength among clopidogrel, prasugrel, and ticagrelor to COX-1 and P2Y12, with ticagrelor emerging as the stronger ligand due to a higher number of bindings and/or closer binding distances. Notably, only prasugrel and ticagrelor demonstrate the ability to bind to the active site of COX-1.Conclusion: Therefore, prasugrel and ticagrelor emerge as potential MAPT agents for ACS patients.Keywords: clopidogrel, prasugrel, ticagrelor, antiplatelet, ACS, in silico, molecular dockin
Green Tea Yoghurt with Encapsulated Lacticaseibacillus paracasei E1 Improves Hepatocyte Damage in High-Fat High-Fructose Diet Mice by Reducing MDA and Increasing SOD
No full textBackground: 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, probioti
Decreased Follistatin Levels as a Risk of Acute Sarcopenia Marker in Elderly
No full textBackground: Acute sarcopenia is an acute muscle loss that has been associated to the frailty and vulnerability of the elderly. Follistatin has been known as a significant marker for sarcopenia, however, studies of follistatin in humans have shown varying results and there have been no studies to date regarding the relationship between follistatin and acute sarcopenia. The aim of this study was to determine changes in follistatin levels as a risk of acute sarcopenia in elderly.Materials and methods: This study was a prospective observational study involving hospitalized elderly. The follistatin level was examined with enzyme-linked immunosorbent assay (ELISA). Meanwhile the determination of acute sarcopenia was done through the measurement of changes in hand grip strength and calf circumference parameters. The data obtained was descriptively analyzed, followed by bivariate and multivariate analysis. A p<0.05 was considered significant.Results: There were 66 subjects in this study. A total of 10 subjects (15.2%) had acute sarcopenia on the 7th day of hospitalization. The cut-off point of decreased follistatin levels was 4.870 with a sensitivity of 82.1% and a specificity of 60%. There was an association between decreased follistatin levels and acute sarcopenia (p=0.01; RR: 6.90; 95% CI: 1.638-29.069). Multivariate analysis results showed that decreased follistatin levels was a significant factor that might influence the occurrence of acute sarcopenia.Conclusion: Since this study showed that decreased follistatin levels might be a risk of acute sarcopenia in the elderly, thus it could be used as a marker of acute sarcopenia, which should be further investigated.Keywords: decreased follistatin levels, acute sarcopenia, elderl
Mechanism of Actions, Efficacy, and Long-term Use of Steroids in Autoimmune Hemolytic Anemia (AIHA)
No full textAutoimmune 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, efficac
Rapidly Growing Ovarian Granulosa Cell Tumor Following Complete Debulking for Suspected Ovarian Cancer with Histopathology Result of Benign Ovarian Cyst
No full textOvarian 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, debulkin
Molecular Docking of Citrus amblycarpa Active Compounds against FTO, Leptin, and Resistin Protein
No full textBackground: Citrus amblycarpa has been known to have various pharmacological activities, such as antioxidants, anticancer, antitumor, hepatoprotective, anti-inflammatory, antidiabetic, antiviral, antibacterial, and antifungal. Hesperidin, naringin, quercetin, rutin, gamma (γ)-aminobutyric acid (GABA), neoeriocitrin, and poncirin from C. amblycarpa were the major constituents that potentially act on some obesity proteins, such as fat mass and obesity-associated (FTO) protein, leptin, and resistin, the emerging targets in the treatment of obesity. This study aimed to investigate the interaction between major active compounds of C. amblycarpa with FTO, leptin and resistin.Materials and methods: The ligands of the docking study were seven major chemical compounds found in peel of C. amblycarpa, i.e., hesperidin, naringin, quercetin, rutin, GABA, neoeriocitrin, and poncirin. FTO, leptin and resistin structure were taken from Protein Data Bank, while the C. amblycarpa compounds were prepared using Open Babel integrated into PyRx 8.0. Molecular docking simulation was performed using Autodock Vina integrated into PyRx 8.0. Virtual prediction and visualization of protein–ligand complexes were analyzed and visualized using Discovery Studio.Results: All major compounds of C. amblycarpa peel used in this study did not have hepatotoxicity and AMES toxicity. Hesperidin had the lowest binding affinity score when interacted with FTO, leptin and resistin compared to other compounds. Moreover, GABA had the highest binding affinity score compared to other compounds.Conclusion: Hesperidin may be a candidate obesity protein antagonist and may have potential as a treatment for obesity.Keywords: Citrus amblycarpa, molecular docking, FTO, leptin, obesity, resisti