Ganoderma lucidum Polysaccharide Peptide Reduces Oxidative Stress and Improves Renal Function in Patient with Cardiometabolic Syndrome

BACKGROUND: Cardiometabolic syndrome is a risk factor for the development of diseases related to cardiovascular disease and decreased renal function. Ganoderma lucidum polysaccharide peptide (GLPP) has been reported to have anti-inflammatory and antioxidant properties. The current study was conducted to investigate the role of GLPP in inflammatory, oxidative stress and renal function markers of cardiometabolic subjects.METHODS: A randomized double-blinded perspective control trial with pre-post design was conducted. Cardiometabolic syndrome subjects were treated with placebo or GLPP for 60 days. Blood serum was collected from each subject before the first capsule consumption and one day after the last capsule consumption. Serum tumor necrosis factor (TNF)-α, high-sensitivity-C-Reactive Protein (hs-CRP) and malondialdehyde (MDA) levels were measured using enzyme-linked immunosorbent assay, while superoxide dismutase (SOD) level was measured using colorimetric assay. Serum urea and creatinine levels were measured using a clinical analyzer. The Cockroft-Gault formula was used to calculate estimated glomerular filtration rate (eGFR).RESULTS: Compared with the control group, the MDA level was significantly reduced, while the SOD level was significantly increased in the GLPP treatment group. Furthermore, serum urea and creatinine were lowered, while eGFR was increased in the GLPP treatment group.CONCLUSION: Treatment of GLPP for 60 days could be beneficial for lowering oxidative stress and improving renal function of patients with cardiometabolic syndrome.KEYWORDS: Ganoderma lucidum, cardiometabolic syndrome, inflammation, oxidative stress, renal functio

Elevated Levels of Urinary Podocyte-Derived Microparticles in Nephrotic Syndrome

BACKGROUND: Nephrotic syndrome (NS) is the most common glomerular disease in childhood. The proposed hypothesis for the pathogenesis of this disease has changed over time, from immune dysregulation theory and systemic circulating factors theory, to the growing recognition of podocytopathies’ role. The existance of podocytopathies is usually examined by using podocyte-derived microparticles (MPs), such as nephrin, podocin, and podocalyxin (PCX). Therefore in this study, the difference between nephrin, podocin, and PCX expressions in NS children and healthy children was investigated.METHODS: An observational cross-sectional study was conducted, involving 33 children with NS and 22 age-matched healthy children as controls. Urine samples were collected from each subject in the early morning, before being processed and incubated with antibodies to detect nephrin, podocin, and PCX. The processed samples were then analyzed with flow cytometer methods.RESULTS: NS subjects had significantly higher expression of all three urinary podocyte-derived MPs compared to the control subjetcs. Nephrin, podocin, and PCX showed good discrimination in NS subjects with the area under curve (AUC) of 0.895, 0.849, and 0.728, respectively.CONCLUSION: This study revealed the differential expression of podocyte proteins in NS subjects compared to healthy controls. This supports the role of podocytopathies in the pathogenesis of NS. Therefore, nephrin, podocin, and PCX might have potentials to be future non-invasive diagnostic tools in glomerular disease.KEYWORDS: nephrin, nephrotic syndrome, podocalyxin, podocin, podocyte, urinary microparticl

Mesenchymal Stem Cell Therapy for Ischemic Stroke in Animal Model: A Systematic Review

BACKGROUND: Stroke is one of many leading causes of death and disability worldwide. Despite decades of research, treatment for stroke recovery is still inadequate. Recently, mesenchymal stem cell (MSC) therapy is considered as one of the potential treatments for stroke due to their capabilities to repair or regenerate damaged tissues, as well as immunomodulators in inflammatory conditions. Many pre-clinical and clinical trials have shown MSC therapy feasibility, safety, and efficacy in treating stroke. However, evidence regarding the optimal treatment plan and factors that can improve stem cell functional outcomes in treating stroke needs to be further explored. Therefore, a systematic review was conducted.METHODS: Recent literatures from 2015-2022 regarding stem cell therapies, specifically MSC on ischemic stroke, were collected from two reliable databases: PubMed and PubMed Central. Collected literatures were properly applied to inclusion-exclusion criteria and appraised critically. Keyword strategies on databases were employed, including both medical subject headings (MeSH).RESULTS: Five literatures from 726 were identified and used for systematic review. All animal model in the literatures were prepared to have middle cerebral artery occlusion. All studies indicated that MSC therapy is a safe and reliable procedure despite the variety of transplantation routes. No report of toxicity, rejection reaction, nor infection on MSC treated groups.CONCLUSION: Stem cell sources, dosages, and delivery routes could be resourceful for future translational studies to ensure the safety and efficacy of MSC therapy for ischemic stroke.KEYWORDS: ischemic stroke, mesenchymal stem cells, regenerative medicine, immunomodulato

Seluang Fish (Rasbora sp.) Oil Improves Interleukin-17 Levels and Disease Activity in Rheumatoid Arthritis

BACKGROUND: Vitamin D has a role in downregulating the proinflammatory cytokines as well as promoting the antiinflammatory pathway in rheumatoid arthritis (RA). Seluang fish (Rasbora sp.) has potency as a new source of vitamin D. Previous study had proven Seluang fish oil efficacy in systemic lupus erythematosus. However, there are no trials that prove its efficacy in RA yet. Hence, this study was conducted to find out the ability of Seluang fish oil to improve proinflammatory cytokines, vitamin D levels, and disease activity in RA.METHODS: A clinical trial with a randomized and double-blind method was done in two groups, each one consisting of 17 RA subjects. One group was given 500 mL of a Seluang fish oil capsule (contains 665 IU cholecalciferol), while the other group was given a placebo daily, for 12 consecutive weeks. Measurements of the RA disease activity score 28 erythrocyte sedimentation rate (DAS28-ESR) and DAS28 C-reactive protein (DAS28-CRP), as well as measurement of interleukin (IL)-6, IL-17, and vitamin D levels by using immunoassay method were performed before and after the supplementation.RESULTS: Significant alterations in the lower levels of IL-17 were observed in the Seluang fish oil group (p=0.031), but not in the placebo group (p=0.320). Reduction of DAS28-ESR (p=0.000) and DAS28-CRP (p=0.000) score demonstrated that the Seluang fish oil supplementation was useful in reducing RA disease activity. No significant shift was observed in either vitamin D (p=0.967) or IL-6 levels (p=0.076) after Seluang Fish Oil supplementation.CONCLUSION: Seluang fish oil is effective in lowering IL-17 levels, DAS28-ESR, and DAS28-CRP, but not in improving vitamin D level or lowering IL-6 level in RA patients.KEYWORDS: rheumatoid arthritis, seluang fish oil, interleukin-6, interleukin-17, vitamin D, DAS2

Increased Levels of IFN-γ, PAI-1, and NT-proBNP are Associated with the Occurrence of Hypoxemia in COVID-19

BACKGROUND: Acute respiratory distress syndrome (ARDS) is one of the severe complications of Coronavirus disease 2019 (COVID-19) that can lead to the occurrence of hypoxemia. Hypoxemia occurs due to the role of pro-inflammatory cytokines and coagulation factors. Several studies have shown that interferon (IFN)-γ, plasminogen activator inhibitor 1 (PAI-1) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are biological markers that can be used to evaluate the severity and prognosis of the disease in severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection. This study was conducted to evaluate the association between IFN-γ, PAI-1, NT-proBNP and hypoxemia in COVID-19 patients.METHODS: This was a cross-sectional study of COVID-19 subjects with hypoxemia. Hypoxemia assessment was performed based on arterial blood gas analysis. IFN-γ and PAI-1 were measured with ELISA, while NT-proBNP levels were measured with Roche NT-proBNP.RESULTS: Fifty-five COVID-19 subjects with hypoxemia were observed. Thirty subjects experiencing moderate to severe hypoxemia and 25 with mild hypoxemia. Levels of IFN-γ, PAI-1, and NT-proBNP were higher in COVID-19 subjects with moderate to severe hypoxemia compared to those with mild hypoxemia (261.14 (121-348.60) pg/mL vs. 145.50 (59.90-348.60) pg/mL, p<0.001; 5.47 (3.50-8.50) pg/mL vs. 3.40 (2.20-9.30) pg/mL, p<0.001; 760 (112-34,066) pg/mL vs. 71 (48-364) pg/mL, p<0.001).CONCLUSION: Elevated levels of IFN-γ, PAI-1, and NT-proBNP are associated with hypoxemia in COVID-19 patients, suggesting that these markers may be useful in assessing hypoxemia in COVID-19 patients.KEYWORDS: IFN-γ, PAI-1, NT-proBNP, hypoxemia, COVID-1

ESAT-6-Ag85C-polyHistag Antigen Fusion is Potential as Vaccine Candidate for Tuberculosis

BACKGROUND: BCG vaccine has been proven to be effective protection against tuberculosis (TB) meningitis and miliary TB. However, for protection against pulmonary TB, the results remains vary widely. Recombinant vaccine consisting of two immunodominant Mtb antigens ESAT-6-Ag85C-polyHistag (EAH) is currently being developed as a new TB vaccine candidate for booster. An immugonecity test for vaccine candidates is required in the initial phase to evaluate cellular immune response. This study was conducted to evaluate the cellular immune response by measuring interferon-gamma (IFN-γ) cytokines produced by T cells after ex vivo stimulation by TB EAH antigen fusion.METHODS: Peripheral blood mononuclear cells supernatant samples were collected from 16 new pulmonary TB subjects, 17 pulmonary TB in treatment subjects, and 10 healthy subjects. Samples were tested for IFN-γ level with enzyme-linked immunosorbent assay (ELISA). Kruskal-Wallis test was used to test the differences between IFN-γ levels among three groups, and followed by post-hoc analysis using Mann Whitney.RESULTS: The median of IFN-γ levels for new pulmonary TB, pulmonary TB in treatment, and healthy subjects were 17.09 (2.65-140.14) pg/mL, 4.36 (2.43-21.41) pg/mL, and 2.91 (2.39-3.85) pg/mL, respectively. There were significant differences of IFN-γ levels between new pulmonary TB group and pulmonary TB in treatment group (p=0.012), between new pulmonary TB group and healthy group (p=0.001), and also between pulmonary TB in treatment group and healthy group (p=0.035).CONCLUSION: Results show that TB EAH could stimulate cell-mediated immune responses in the three groups, with the highest IFN-γ levels are found in new pulmonary TB group, suggesting a potential immunodominant antigen fusion for vaccine candidate development.KEYWORDS: Ag85C, ESAT-6, immunogenicity test, IFN-γ, TB vaccine candidate, tuberculosi

Amino Acid Profile of Luminal A and B Subtypes Breast Cancer

BACKGROUND: Amino acids are important for proliferation and maintenance of tumor cells. Breast cancer patients were found to have significant changes in the number of amino acids, which are assumed to be correlated with the molecular subtypes of breast cancer. Therefore, current study was conducted to analyze plasma amino acids in breast cancer patients with luminal A and B subtypes.METHODS: Breast cancer and control subjects were recruited, and venous blood was collected for the measurement of plasma amino acids. Total 19 plasma amino acids were measured using reverse-phase high-performance liquid chromatography with C18 column. Mean comparison for normally distributed and homogeneous data was further analzyed using independent sample T-test, with p<0.05 was considered as significant.RESULTS: From total 19 amino acids, only 7 amino acids; cysteine, glutamic acid, histidine, ornithine, threonine, tyrosine, valine, were statistically different between the healthy control and breast cancer subjects. Eventhough no amino acids was found to be statistically different between breast cancer subjects with luminal A and B subtypes, but some amino acids were found to be significantly different when correlated to various breast cancer risk factors.CONCLUSION: Amino acid profile of patients with Luminal A and B subtypes of breast cancer differs compared to healthy controls and is also correlated with breast cancer risk factors. Increase in cysteine level in Luminal A subtype patients and decrease of alanine and leucine in Luminal B subtype patients can be used as a biomarker.KEYWORDS: amino acid, plasma, breast cancer, risk factor, biomarke

Effect of Three and Six Months of Vitamin D Supplementation on Glycemic Control and Insulin Resistance in Type 2 Diabetes Mellitus: Randomized Placebo-controlled Trial

BACKGROUND: 25(OH)D level is correlated with insulin secretion and tissue sensitivity to insulin. Administration of vitamin D supplements may reduce tissue resistance to insulin in type 2 diabetes mellitus (T2DM), but a number of studies found conflicting results. The present study was to measure the results of administration of vitamin D supplements for 3 and 6 months regarding HbA1c, fasting blood glucose (FBG), insulin and tissue resistance to insulin in T2DM cases.METHODS: A randomized double-blind placebo-controlled trial was conducted in T2DM patients with ≤3 years duration. Subjects were randomly divided into two groups: 47 subjects received daily 5000 IU vitamin D supplementation and 47 subjects received daily placebo as control. After supplementation for 3 and 6 months, homeostatic model assessment for tissue resistance to insulin (HOMA-IR), insulin, HbA1c, and FBG were examined.RESULTS: Supplementation of daily 5000 IU vitamin D for 3 months increased 25(OH)D level in the vitamin D group from 12.50±5.28 to 43.57±17.14 ng/mL, and after 6 months the 25(OH)D level was 38.38±17.64 ng/mL. Both groups showed significant differences after 3 and 6 months regarding HOMA-IR (p=0.033 and p=0.031), insulin (p=0.034 and p=0.013), but not FBG (p=0.296) and HbA1c (p=0.360). In both groups, HOMA-IR and insulin increased although the increase in the control group was greater than in the vitamin D group. The difference between the control and vitamin D groups was significant.CONCLUSION: Vitamin D supplementation for 3 and 6 months may lead to improvement HOMA-IR but not for FBG and HbA1c in the vitamin D group as compared with the control group in T2DM cases.KEYWORDS: vitamin D, T2DM, HbA1c, blood glucose, insulin, tissue resistance to insuli

Increased hs-CRP and Sepsis Influence the Occurrence of Thrombocytopenia in Severe and Critically Ill COVID-19 Patients Receiving Anticoagulants

BACKGROUND: Despites its benefits, as one of COVID-19 principal treatments, anticoagulant raises a significant concern regarding the anticoagulant-related thrombocytopenia. However, up to date, there is lack of study examining anticoagulantinduced thrombocytopenia during COVID-19, hence this study was conducted to determine the factors inducing anticoagulant-induced thrombocytopenia in COVID-19 patients.METHODS: An observational cross-sectional study of 106 anticoagulant-treated COVID-19 subjects was conducted. Blood serum was drawn from subjects, then platelets, prothrombin time (PT), activated partial thromboplastin (aPPT), international ratio (INR), D-dimer, ferritin, fibrinogen, and high-sensitivity C-reactive protein (hs-CRP), were measured. For thrombocytopenia risk assessment, the 4T score was calculated. To assess the risk of thrombocytopenia. Statistical analysis using Chi-square and Mann-Whitney U test were performed and followed by multivariate analysis to examine the correlation among the thrombocytopenia risk factors.RESULTS: Significant differences were identified in the length of stay (LOS) (p=0.04), disease severity (p=0.021), sepsis (p=0.006), hs-CRP (p=0.003), and mortality rate (p=0.028) between thrombocytopenia and nonthrombocytopenia groups. A multivariate analysis through linear and logistic regression disclosed an increase in hs-CRP (OR=-0.29; p=0.045) and sepsis (OR=4.32; p=0.03) that precipitate the thrombocytopenia events.CONCLUSION: In severe and critically ill COVID-19 patients, the occurrence of thrombocytopenia was followed by an increase in inflammatory parameters such as D-dimer, fibrinogen, ferritin, hs-CRP and prolonged coagulation. The increase in hs-CRP and sepsis may raise the risk of thrombocytopenia, especially in severe and crtically ill cases of COVID-19.KEYWORDS: COVID-19, anticoagulant, thrombocytopenia, inflammation, infectious diseas

A Double-Blind, Randomized Controlled Trial of Hydroxychloroquine for Cognitive Dysfunction and Inflammatory Biomarkers in Systemic Lupus Erythematosus Patients in Indonesia

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune condition characterized by persistent, chronic inflammation that damages organ tissue. One of the symptoms that is often found in SLE is cognitive dysfunction. Hydroxychloroquine is recommended for the treatment of all levels of SLE. This study was conducted to prove the influence of hydroxychloroquine on improving cognitive function and inflammatory biomarkers compared to standard therapy.METHODS: The study adopted randomized controlled trial (RCT) in SLE patients with cognitive dysfunction who met the inclusion criteria. The treatment group consisted of 26 subjects who received hydroxychloroquine 200 mg/day for 8 weeks and standard therapy, while the control group consisted of 29 subjects who were given standard therapy only. Examination of Montreal Cognitive Assessment (MoCA)-INA, interleukin (IL)-6, IL-4, interferon (IFN)-α, and C-reactive protein (CRP) scores was carried out at the beginning and the end of the study. The unpaired variables were examined with independent T-test or the Mann-Whitney test, while the paired variables were examined with paired T-test or Wilcoxon signed rank test. The Spearman correlation test was used to measure correlation between variables.RESULTS: A total of 55 subjects participated and completed the study. The result showed a significant relationship between hydroxychloroquine and decreasing levels of IL-6 and IL-4 (p0.05) in both groups.CONCLUSION: Hydroxychloroquine decreases the levels of IL-6 and IL-4, but has no effect on cognitive function, levels of IFN-α and CRP.KEYWORDS: hydroxychloroquine, systemic lupus erythematosus, cognitive dysfunction, inflammatio