Coronary artery disease (CAD) remains the leading cause of mortality and morbidity around the world. Despite significant progress in the diagnosis and treatment of cardiovascular diseases, still there is a clinical need to identify novel biomarkers for early diagnosis and treatment of CAD. The aim of the study is to investigate circulating miRNAs in CAD patients to identify potential biomarkers for early detection and therapeutic management of CAD. We assessed the expression of different candidate miRNAs (miR-21-5p, miR-133a-3p, miR-221-3p, miR-451a and miR-584-5p) in plasma from 50 CAD patients and 50 controls by qRT-PCR analysis. The expression levels of miR-133a-3p (fold change (FC): 28.05, p < 0.0001), miR-451a (FC: 27.47, p < 0.0001), miR-584-5p (FC: 7.89, p < 0.0001), miR-21-5p (FC: 5.35, p < 0.0001) and miR-221-3p (FC: 5.03, p < 0.0001) were significantly up-regulated in CAD patients compared to controls. Receiver operating characteristic curve analysis showed that miR-133a-3p and miR-451a were powerful biomarkers for detecting CAD. Our results suggested that miR-21-5p, miR-133a-3p, miR-221-3p, miR-451a and miR-584-5p may serve as independent biomarkers for CAD. Further, the combination of miR-133a-3p and miR-451a could be used as a specific signature in CAD diagnosis.
Diabetes mellitus is a group of metabolic disorders that has risen to become the third most common cause in humans in recent years. The development of new bioactive substances from natural sources is a relatively new area. Flavonoids are believed to have a variety of beneficial properties in nature, including anti-inflammatory, antimicrobial, anticancer, antioxidant, neuroprotective, and anti-HIV properties. 15 naturally occurring flavonoids docked with the selected target aldose reductase. We report the optimal binding of Acumitin, Agathisflavone, Agehoustin B, and alpha-Toxicarol with aldose reductase for further consideration in drug discovery for T2DM.
Rheumatic heart disease (RHD) is a cardiovascular disease caused by an autoimmune response to group A Streptococcus (GAS) infection resulting in the damage of heart valves. RHD is the most commonly acquired heart disease among children and young adults with a global burden of over 40 million cases accounting for 306,000 deaths annually. Inflammation in the heart valves caused due to molecular mimicry between the GAS antigens and host cardiac proteins is facilitated by cytokines, cross-reactive antibodies and CD4+ T cells. The complex interaction between genetic and environmental factors linked with erratic events leads to the loss of immunological tolerance and autoimmunity in RHD. Despite extensive research on the etiopathogenesis of RHD, the precise mechanism underpinning the initiation of acute rheumatic fever (ARF) to the progression of RHD still remains elusive. Mounting evidences support the contribution of the human microbiome in the development of several immune-mediated diseases including rheumatoid arthritis, juvenile idiopathic arthritis, Kawasaki disease, inflammatory bowel disease and type 1 diabetes. The microbiome and their metabolites could play a crucial role in the integrity of the epithelial barrier, development of the immune system, inflammation and differentiation of T cell subsets. Consequently, microbiome dysbiosis might result in autoimmunity by molecular mimicry, epitope spreading and bystander activation. This review discusses various aspects of the interaction between the microbiome and the immune system in order to reveal causative links relating dysbiosis and autoimmune diseases with special emphasis on RHD.
Natural remedies from medicinal plants are known to be effective and reliable appropriate medicine for illnesses. The current research examined Plectranthus amboinicus’ anti diabetic property by docking the bioactive compounds of certain target proteins. We document the molecular docking analysis of bioactive compounds from Plectranthus amboinicus with protein Glucokinase. Molecular docking experiments were carried out in PyRx software. Results of these docking experiments showed that most of the compounds showed very strong interaction with the target protein Glucokinase. Based on the scoring parameters we have selected best four compounds (Rutin, Salvianolic acid, Luteolin and Salvigenin) which showed very good docking score and hydrogen bond interaction for diabetics.
Osteoporosis is a skeletal disease that is both systemic and silent characterized by an unbalanced activity of bone remodeling leading to bone loss. Rising evidences demonstrate that thyroid stimulating hormone (TSH) has an important role in the regulation on the metabolism of bone. However, TSH regulation on human osteoblast essential transcriptional factors has not been identified. Current study examined the role of TSH on human osteoblastic Runx2 expression and their functional genes by in vitro and in slico analysis. Human osteoblast like (HOS and SaoS-2) cells were cultured with DMEM and treated with hTSH at the concentration of 0.01 ng/mL and 10 ng/mL. After treatment, osteoblastic Runx2 and IGF-1R beta expression were studied using RT-PCR and western blot analysis. TSH treatment induced osteoblastic essential transcriptional factor, Runx2 in HOS and SaOS2 cells on 48 h duration and elevated the expression of IGF-IR β gene and Protein in SaoS-2 cells. TSH also promotes Runx2 responsive genes such as ALP, Collagen and osteocalcin in SaOS2 cells on day 2 to day 14 of 10 ng/mL of treatment and favors’ matrix mineralization matrix in these cells. In addition, TSH facilitated human osteoblastic cells to mineralize their matrix confirmed by day 21 of alizarin red calcium staining. In silico study was performed to check CREB and ELK1 interaction with Runx2. Results of in silico analysis showed that TSH mediated signalling molecules such as CREB and ELK1 showed interaction with Runx2 which involve in osteobalstic gene expression and differentiation. Present findings confirm that TSH promotes Runx2 expression, osteoblastic responsive genes and bone matrix formation.
Background: Gastric adenocarcinoma in Indian patients’ is on the rise. A high level of plasma von Willebrand factor (vWF) is associated not only with the development of cancerassociated thrombosis but also with the degree of malignancy, the rate of metastasis, andcancer prognosis. Aims and Objectives: The aim of this study was to study the association of vWF with tumor location, TNM staging, and grades of tumor differentiation in gastric adenocarcinoma and to assess the usefulness of circulating vWF levels as a potential biomarker for gastric adenocarcinoma. Materials and Methods: This study is a prospective observational study done in the Department of Surgical Gastroenterology, Madurai Medical College, Madurai, over a period of 2 years between September 2020 and August 2022. Fifty cases of gastric cancer and 50 controls were recruited and vWF levels were analyzed. Results: Among the 50 gastric cancer patients, 8% belonged to Stage II, 62% belonged to Stage III, and 30% belonged to Stage IV. vWF was elevated in Gastric Cancer patients compared to control group. Mean value of vWF in Cases and Control population was 3.68 ng/ml and 0.58 ng/ml respectively (p value 0.0005). Pertaining to Stage, the vWF value was, Stage II – 4.7, Stage III – 3.3, and Stage IV – 4.1 ng/mL. With respect to tumor differentiation, the vWF values were, poorly differentiated – 4.7, moderately differentiated – 3.0, and well differentiated – 3.9 ng/mL. Conclusion: vWF values were significantly elevated in gastric cancer patients. Based on the results, vWF can be used as a surrogate marker to predict the tumor differentiation in patients, thereby prognosticating the disease. Stage-wise, there was no significantdifference in the vWF values.