Distinctive Microbiome Type Distribution in a Young Adult Balinese Cohort May Reflect Environmental Changes Associated with Modernization.

An important public health question is understanding how changes in human environments can drive changes in the gut microbiota that influence risks associated with human health and wellbeing. It is well-documented that the modernization of societies is strongly correlated with intergenerational change in the frequency of nutrition-related chronic diseases in which microbial dysbiosis is implicated. The population of Bali, Indonesia, is well-positioned to study the interconnection between a changing food environment and microbiome patterns in its early stages, because of a recent history of modernization. Here, we characterize the fecal microbiota and diet history of the young adult women in Bali, Indonesia (n = 41) in order to compare microbial patterns in this generation with those of other populations with different histories of a modern food environment (industrialized supply chain). We found strong support for two distinct fecal microbiota community types in our study cohort at similar frequency: a Prevotella-rich (Type-P) and a Bacteroides-rich (Type-B) community (p < 0.001, analysis of similarity, Wilcoxon test). Although Type-P individuals had lower alpha diversity (p < 0.001, Shannon) and higher incidence of obesity, multivariate analyses with diet data showed that community types significantly influenced associations with BMI. In a multi-country dataset (n = 257), we confirmed that microbial beta diversity across subsistent and industrial populations was significantly associated with Prevotella and Bacteroides abundance (p < 0.001, generalized additive model) and that the prevalence of community types differs between societies. The young adult Balinese microbiota was distinctive in having an equal prevalence of two community types. Collectively, our study showed that the incorporation of community types as an explanatory factor into study design or modeling improved the ability to identify microbiome associations with diet and health metrics.

High C-Reactive Protein/ Albumin Ratio Predicts Mortality and Hemorrhage in Stroke Patients Undergoing Mechanical Thrombectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: Stroke outcomes are multifactorial, and the C-Reactive Protein to Albumin Ratio (CAR) has emerged as a potential prognostic marker. This study aims to evaluate CAR prognostic significance in stroke. METHODS: Systematic searches across ScienceDirect, Medline, and Cochrane databases identified longitudinal studies. Unfavorable outcomes, including poor prognosis (modified rankin scale> 2), mortality, and severe complications like hemorrhage or restenosis, were considered. Analyses for unfavorable outcomes were conducted based on prior intervention, stroke type, and outcome type. RESULTS: The meta-analysis included 12 cohort studies comprising 5042 participants. Elevated CAR (OR: 1.72; 95% confidence interval [CI]: 1.17-2.52; P = 0.01) and CRP (OR: 1.91; 95% CI: 1.31-2.77; P < 0.001) levels on admission were associated with unfavorable outcomes; no such association was observed for albumin (OR: 0.66; 95%CI: 0.24-1.80; P = 0.42). Elevated CAR levels were associated with unfavorable outcomes in patients undergoing mechanical thrombectomy (odds ratio [OR]: 2.70; 95% CI: 1.14-6.38; P < 0.02) and those with ischemic stroke (OR: 1.99; 95% CI: 1.24-3.18; P < 0.001), but no significant association was found in patients with hemorrhagic stroke. Furthermore, concerning specific outcomes, high CAR levels were associated with mortality (OR: 1.71; 95% CI: 1.00-2.95; P = 0.05) and hemorrhage (OR: 6.02; 95% CI: 1.61-23.87; P = 0.05). The area under the curve for CAR was 0.72 (0.68-0.76), with a sensitivity of 0.61 (0.49-0.71) and specificity of 0.73 (0.64-0.81). CONCLUSIONS: Elevated CAR emerges as an effective marker in assessing unfavorable outcomes in stroke patients with moderately high sensitivity and specificity. High CAR levels exhibited statistically significant mortality and hemorrhage in stroke patients undergoing mechanical thrombectomy.

New-onset diabetes in COVID-19: The molecular pathogenesis.

Diabetes mellitus (DM) is still a challenging metabolic disease worldwide. In the current situation, the world is facing a COVID-19 pandemic due to SARS-CoV-2 infection. DM is one of the comorbid conditions that can worsen the severity of the COVID-19 condition. Surprisingly, SARS-CoV-2 infection can induce new-onset diabetes, a condition in which acute hyperglycemia occurs and may develop into a complication in nondiabetic patients. Angiotensinconverting enzyme 2 (ACE2) is a crucial entry factor for SARS-CoV-2 infection. ACE2 will bind to the spike protein of SARS-CoV-2, potentially initiating a damaging process in many tissues in the human body, including metabolic tissues. This mechanism suggests a potential role of ACE2 in the pathogenesis of diabetes since ACE2 has been proven to localize in essential metabolic tissues, one of which is the acini and islets part of the pancreas. This interrelated ACE2 in COVID-19 and DM is thought of as the mechanism that induces new-onset diabetes in COVID-19 patients. This review will thoroughly describe the current findings and theories regarding the molecular mechanism of SARS-CoV-2-induced new-onset diabetes and the possible therapeutic intervention.

Analysis of PD-L1 Expression in Breast Cancer: A Systematic Review and Meta-Analysis in Asian Population.

OBJECTIVE: This study aimed to investigate the level of PD-L1 protein expression in patients with BCs who were of Asian descent. METHODS: Three databases were conducted on this article up to August 10th, 2022. The reference lists of the publications were examined for further studies, and in cases of duplicates, a study with a larger sample size was added. In survival analysis, the hazard ratio (HR) was applied to the circumstances characterized by the frequency of occurrences, and for the clinicopathological characteristic, the best-adjusted odds ratio (OR) with a 95% confidence interval (CI) was employed. The Newcastle-Ottawa Scale (NOS) was utilized to evaluate selection criteria, comparison, and exposure to establish the quality of the technique in the under-consideration studies. The Z test determined the association analysis of OS, DFS, and clinicopathological characteristics with PD-L1 expression. RESULT: All eight trials for OS and six for DFS were considered, with 4.111 and 3.071 participants, respectively. Overexpression of PD-L1 was linked to a reduced OS compared to individuals with undetectable expression (HR= 1.58, 95% CI 1.04-2.40; P=0.03). We analyzed clinicopathological features, and it elevated in individuals with histological grade III (OR=2.39, 95% CI 1.26-4.54; P=0.008) and positive node (OR=0.68, 95% CI 0.48-0.97; P<0.05). CONCLUSION: Overexpression of PD-L1 was associated with a shorter OS in BCs patients. High PDL1 was higher in persons with nodal positivity and histological grade III.

The Potential of the Flavonoid Content of Ipomoea batatas L. as an Alternative Analog GLP-1 for Diabetes Type 2 Treatment-Systematic Review.

Ipomoea batatas L. (IBL) has gained significant popularity as a complementary therapy or herbal medicine in the treatment of anti-diabetes. This review seeks to explore the mechanism by which flavonoid compounds derived from IBL exert their anti-diabetic effects through the activation of GLP-1. The review article refers to the PRISMA guidelines. In order to carry out the literature search, electronic databases such as Science Direct, Crossref, Scopus, and Pubmed were utilized. The search query was based on specific keywords, including Ipomoea batatas OR sweet potato AND anti-diabetic OR hypoglycemic. After searching the databases, we found 1055 articles, but only 32 met the criteria for further review. IBL contains various compounds, including phenolic acid, flavonols, flavanols, flavones, and anthocyanins, which exhibit activity against anti-diabetes. Flavonols, flavanols, and flavones belong to a group of flavonoids that possess the ability to form complexes with AlCl3 and Ca2+. The intracellular L cells effectively retain Ca2+, leading to the subsequent release of GLP-1. Flavonols, flavones, and flavone groups have been found to strongly interact with DPP-IV, which inhibits the degradation of GLP-1. The anti-diabetic activity of IBL is attributed to the mechanism that effectively increases the duration of GLP-1 in the systemic system, thereby prolonging its half-life.

Clinicopathological and Prognostic Significance of Ubiquitin-Specific Protease 39 Overexpression in solid Cancers: A Meta-Analysis.

OBJECTIVES: This meta-analysis aimed to evaluate the association between USP39 expression, the prognosis of patients with solid cancer, and to identify the clinicopathological characteristics of these patients. MATERIAL AND METHOD: This study was carried out using PRISMA strategy. Pubmed, ScienceDirect, Google Scholar, Ebsco, Cochrane Library electronic databases were searched for relevant studies published up to April 2022. 14 studies was included in this study. Hazard ratio (HR) and 95% confidence interval (CI) data were collected, including number of samples, detection methods, number of sample with high USP39 expression, and cut-off value. HR and 95% CI was used to evaluate the prognostic value of USP39 expression. Odds ratio (OR) with 95% CI was used to assess the effect of USP39 expression on clinicopathological parameters. RESULTS: Qualitative analysis using 14 included studies and quantitative analysis using 7 included studies. We found that USP39 expression has significant risk for histological grade (OR 3.14, CI 95% 2.15-4.58, p<0.001), TNM stage (OR 2.23, CI 95% 1.66-3.00, p<0.001), tumor size (OR 2.17, CI 95% 1.56-3.03, p<0.001), lymph node metastasis (OR 2.31, CI 95% 1.23-4.33, p=0.009), vascular invasion (OR = 1.76, 95% CI = 1.13-2.73, p=0.01). Furthermore, high expression of USP39 protein was associated with worse OS (OR 1.17, CI 95% 1.13-1.21, p<0.001) and DFS (OR 1.39, CI 95% 1.23-1.57, p<0.001) in cancer patients. CONCLUSION: It can be concluded that USP39 has a significant prognostic value in patients with solid cancer and was found to have a significant relationship in the clinicopathology of solid cancer patients.

The Risk of Antipsychotic Drugs on Breast Cancer: A Systematic Review and Meta-analysis.

Objectives: To investigate the association between the consumption of antipsychotic drugs and breast cancer. Methods: In this systematic review and meta-analysis study, relevant studies were extracted from different databases including PubMed, ScienceDirect, Cochrane, Medline, and additional sources. The selected studies were statistically analyzed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Of a total of 11 studies selected, five were case-control type and six were cohort type. The overall study quality was 6.7. Meta-analysis of the five case-control studies (which together had 81 766 breast cancer patients and 1 150 316 control participants) showed no significant association between the overall use of antipsychotic drugs and the incidence of breast cancer (odds ratio = 1.06; 95% CI: 0.94-1.19; p =0.36). Q-test results showed evidence of heterogeneity (p < 0.10) in the overall analysis. The I2 statistical assessment also show evidence of heterogeneity (I2> 75%). Conclusions: The use of antipsychotic drugs does not significantly increase the risk of breast cancer.

Pretreatment Leukocyte Count Ratios as Metastatic Predictive Factors in Luminal Type Breast Cancer.

OBJECTIVE: Molecular based predictive biomarkers have been developed but still unaffordable in developing countries. The leukocyte ratio is known as a promising, affordable and practical biomarker. However, the evidence to support their application is still lacking, especially from developing countries. Therefore, this study aimed to evaluate the association between leukocytes count ratios as predictive markers of metastasis in luminal type breast cancer. METHODS: A retrospective cross-sectional study was conducted using breast cancer patient data obtained at Sanglah General Hospital (2016-2020). Complete blood count (CBC) and histopathological records of the patients were collected and the basophil-to-lymphocyte ratio (BLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) were calculated. Tumor stadium was classified into early (I-II) and advance (III-IV) stage while distant metastasis was classified into M0 and M1. Data were then analyzed using ROC curve and then followed by chi square and logistic regression analysis to obtain OR value. RESULTS: Two hundred eighty-three  luminal breast cancer patient data were used in this study with mean age 49.27 ± 9.451. Most of the patient had advanced disease (177 patients; 62.5%) while metastatic disease accounted for 54 patients (19.1%) of all patients. Patients with metastatic disease had higher median of BLR, MLR, NLR and PLR (0.043 ± 0.025, p=0.034; 0.289 ± 0.285, p=0.008; 3.489 ± 5.027, p=0.044; 159.538 ± 127.79, p=0.008) than patients without metastasis. The AUC (sensitivity and specificity) of BLR, MLR, NLR and PLR in predicting metastasis were 0.593 (51%; 65%), 0.616 (35%; 89%), 0.588 (46%; 75%) and 0.615 (40%; 81%), respectively. In multivariate risk analysis model, patients with metastasis were found in high BLR (Adjusted OR: 2.045; 95%CI=1.123-3.723; p=0.019), MLR (Adjusted OR: 4.862; 95%CI=2.401-9.844; p<0.001), NLR (Adjusted OR: 2.727; 95%CI=1.475-5.044; p=0.001) and PLR (Adjusted OR: 3.061; 95%CI=1.618-5.792; p=0.001). CONCLUSION: Pretreatment leukocyte ratios are potential predictive markers for metastasis. However, these findings need to be validated in larger and prospective studies with more comprehensive design.

Polymorphisms of vascular endothelial growth factor-2578C/A rs699947 are risk factors for diabetic retinopathy in type-2 diabetes mellitus patients in Bali, Indonesia.

BACKGROUND: Diabetic retinopathy (DR) is one of the complications in diabetes mellitus (DM) which caused by microvascular-damage in the retina due to long termmetabolic changes in diabetes. To date, there has been much research targeted on the determinant of genetic identification in DR patients. In DR, Vascular Endothelial Growth Factor (VEGF) gene is accountable for breaking down the blood-retinal barrier and implicated in the role of neovascularization. It is thought that the polymorphism of VEGF -2578C/A (rs699947) contributed to the development of diabetic retinopathy in type 2 DM. AIM: To determine whether the polymorphisms of VEGF-2578C/A are the risk factors for DR in type 2 DM patients in Bali, Indonesia. METHODS: This study is a case-control model comparing 33 cases DR patients in type-2 diabetes mellitus and 35 cases of non-DR as controls in Balinese ethnic. Polymorphisms of VEGF-2578C/A were examined by PCR analysis and DNA sequencing on rs699947 to identify any variation in A/C/T allele distribution. Chi-square test was used to analyze the data and determine the relation of polymorphism and DR. RESULTS: This research showed the genetic variation existence in VEGF-2578C/A polymorphism significantly (p = 0,000) with C allele was higher in the DR group, in contrast, A and T allele were greater in the non-DR group compared to DR group. The result showed that C allele in VEGF-2578 contributed as a risk factor (OR = 13.05; 95% CI = 2.69-63.18; p = 0.001) for DR in type-2 DM (T2DM) patients in Bali, Indonesia. CONCLUSION: Polymorphism of VEGF-2578C/A (rs699947) allele distribution can be concluded as a risk factor of DR within T2DM patients in Bali, Indonesia. This study may also be used to expand the knowledge in managing DR patients at an earlier stage to avoid further complications.

Chaperone-Based Therapeutic Target Innovation: Heat Shock Protein 70 (HSP70) for Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is still a global health problem. Current T2DM treatments are limited to curing the symptoms and have not been able to restore insulin sensitivity in insulin-sensitive tissues that have become resistant. In the past decade, some studies have shown the significant role of a chaperone family, heat shock protein 70 (HSP70), in insulin resistance pathogenesis that leads to T2DM. HSP70 is a cytoprotective molecular chaperone that functions in protein folding and degradation. In general, studies have shown that decreased concentration of HSP70 is able to induce inflammation process through JNK activation, inhibit fatty acid oxidation by mitochondria through mitophagy decrease and mitochondrial biogenesis, as well as activate SREBP-1c, one of the lipogenic gene transcription factors in ER stress. The overall molecular pathways are potentially leading to insulin resistance and T2DM. Increased expression of HSP70 in brain tissues is able to improve insulin sensitivity and glycemic control specifically. HSP70 modulation-targeting strategies (including long-term physical exercise, hot tub therapy (HTT), and administration of alfalfa-derived HSP70 (aHSP70)) in subjects with insulin resistance are proven to have therapeutic and preventive potency that are promising in T2DM management.

The therapeutic potential of RNA interference in controlling HIV-1 replication.

Human immunodeficiency virus type 1 (HIV-1) has long been a major problem to handle. Its existence is incurable (yet) and has reached pandemic proportions despite strictly-controlled epidemiological surveillance. The current treatment regimen involves the use of multiple antiretroviral agents (known as HAART) is very complex and may harm patients through its serious risk of toxicities. Moreover, the continuing emergence of drug resistance further threaten the future therapy, thereby necessitates another treatment strategy i.e. specific and efficient with low or minimal toxicity. RNAi is a potent candidate for the future treatment of HIV-1. It involves an immune-based silencing mechanism (post transcriptional gene silencing/PTGS) that uses small sequence of RNA (21-25 nucleotides in length) to inhibit almost every genes expression, including HIV-1 RNA and its mRNA byproducts. Since RNAi uses sequence of base pairs, it can be designed very specific and homologues to silence the genes in favor. RNAi works either through binding with HIV-1 to inhibit provirus integration into cellular genome or with mRNA products to inhibit certain genes expression (e.g. p24/Gag, Vif, Rev) that plays an important role in HIV-1 infectivity to knockdown its virulence capacity. Given the need for a treatment modality that are sequence-specific and able to overcome the highly mutation rate of virus like HIV-1, also by its enormous power to inhibit HIV-1 expression through various target sites, it is considered essential to discuss the molecular mechanism of RNAi, progresses that have been achieved, and future directions for its use in clinical settings.

Polymorphisms of Aldose Reductase (ALR2) Regulatory Gene are Risk Factors for Diabetic Retinopathy in Type-2 Diabetes Mellitus Patients in Bali, Indonesia.

AIM: The study aimed to elucidate whether the polymorphisms of the aldose reductase regulatory gene were risk factors for Diabetic Retinopathy (DR) in type-2 diabetes mellitus (T2DM) patients in Bali. METHODS: This is a case-control study including 35 cases of T2DM patients with DR paired with 35 cases with non-DR as controls. PCR analysis and DNA-sequencing were carried out to detect the C(-106)T and C(-12)G polymorphisms at the regulatory region of Aldose Reductase (ALR2) gene. Genotype and allele distributions were analyzed by Chi-squared test and independent t-and Mann-Whitney U tests were used to analyze other data. RESULTS: Among all subjects in both groups, the baseline characteristics were homogenous except for systolic blood pressure, fasting blood glucose and 2-hours post-prandial blood glucose. This study found two polymorphisms, C(-104)T and C(-9)G, in the regulatory region of ALR2 gene. The result showed that the C(-104)T polymorphism was a risk factor for DR (OR=36; 95% CI = 4.43-292.85; p=0.001), but not the C(-9)G polymorphism (OR=1.28; 95% CI=0.48-3.38; p=0.621). Other findings in the study revealed that CC/CC haplotype is a protective factor for DR (OR=0.198; p=0.002), whereas CT/CC and CT/CG haplotypes as risk factors for DR with OR=15.58; p=0.002 and OR=2.29; p=0.005 respectively. CONCLUSION: It can be concluded that C(-104)T polymorphism in the regulatory region of Aldose Reductase (ALR2) gene was the risk factor for DR among T2DM patients in Bali, Indonesia. However, small sample size, systolic blood pressure, fasting blood glucose and 2-hours post-prandial blood glucose could affect our finding.