Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by severe pain, inflammation, and joint deformity. Currently, it affects 1% of the population, with a projection to exceed 23 million cases by 2030. Despite significant advancements, non-steroidal anti-inflammatory drugs (NSAIDs), the first line of treatment, are associated with a range of adverse effects.
View Article and Find Full Text PDFIntroduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial infiltration and pannus formation, and its rising incidence is significantly contributing to the global disability rate. Despite advances in biological drugs, no treatment has successfully cured or averted its progression. Consequently, natural drugs are being explored as alternative therapeutic strategies.
View Article and Find Full Text PDFThe increasing prevalence of multi-morbidities, particularly the incidence of breast cancer in diabetic/osteoarthritic patients emphasize on the need for exploring the underlying molecular mechanisms resulting in carcinogenesis. To address this, present study employed a systems biology approach to identify switch genes pivotal to the crosstalk between diseased states resulting in multi-morbid conditions. Hub genes previously reported for type 2 diabetes mellitus (T2DM), osteoarthritis (OA), and triple negative breast cancer (TNBC), were extracted from published literature and fed into an integrated bioinformatics analyses pipeline.
View Article and Find Full Text PDFNanotechnology has transformed drug delivery, offering opportunities to enhance treatment outcomes while minimizing adverse effects. This study focuses on gelatin-coated cobalt and manganese ferrite nanoparticles for potential drug delivery applications. The synthesis involved a co-precipitation method, and the nanoparticles were characterized using various techniques, including X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, and vibrating sample magnetometer (VSM).
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that is most prevalent in elderly individuals, especially in developed countries, and its prevalence is now increasing in developing countries like Pakistan.
Objective: Our goal was to characterize key genes and their levels of expression and related molecular transcriptome networks associated with AD pathogenesis in a pilot case-control study in a Pakistani population.
Methods: To obtain the spectrum of molecular networks associated with pathogenesis in AD patients in Pakistan (comparing cases and controls), we used high-throughput qRT-PCR (TaqMan Low-Density Array; = 33 subjects) coupled with Affymetrix Arrays ( = 8) and Ingenuity Pathway Analysis (IPA) to identify signature genes associated with Amyloid processing and disease pathways.
Rheumatoid arthritis (RA), is marked by joint inflammation leading to pannus formation which results in cartilage destruction promoting bone erosion. The pathological hallmark of RA includes synovial hyperplasia and synovial angiogenesis. Active tissue neovascularization is observed in RA.
View Article and Find Full Text PDFChronic hyperglycemia and oxidative stress in Type 2 Diabetes Mellitus trigger cellular dysfunction via the formation of Advanced Glycation End Products (AGEs), resulting in dicarbonyl stress. Glyoxalase-1 (Glo-1) is the main defense against dicarbonyl stress. The aim of this study was to explore any cross-talk between Glo-1 and markers of hyperglycemia and oxidative stress.
View Article and Find Full Text PDFBackground: Synovial fibroblasts in rheumatoid arthritis (RAFLS) exhibit a pathological aberration of glycolysis and glutaminolysis. Henceforth, we aimed to investigate if dual inhibition of these pathways by phytobiological compound c28MS has the potential of synergistic therapy for arthritis by targeting both glucose and glutamine metabolism.
Methods: The presence of HK2 and GLS across various cell types and associated gene expression in human synovial cells and a murine model of arthritis was evaluated by scRNA-seq.
The bidirectional causal relationship between type 2 diabetes mellitus (T2DM) and breast cancer (BC) has been established by numerous epidemiological studies. However, the underlying molecular mechanisms are not yet fully understood. Identification of hub genes implicated in T2DM-BC molecular crosstalk may help elucidate on the causative mechanisms.
View Article and Find Full Text PDFThis study aimed to assess the anti-rheumatic potential of and to evaluate its bioactive small molecules for their beneficial effects in the management of rheumatoid arthritis. bioactivity assays were performed to assess the healing potential of and statistical analysis was performed by using the linear regression technique. analysis was performed to identify the key inhibitors of the disease to target TNF-α.
View Article and Find Full Text PDFGlyoxalase-1 (Glo-1) is a key member of the Glyoxalase system, the primary line of defense against dicarbonyl stress which, in tandem, with reduced levels of expression or activity of Glyoxalase-1 enzyme, has been implicated in various human diseases like type 2 diabetes mellitus (T2DM) and its vascular complications. The association of Glo-1 single nucleotide polymorphisms with genetic susceptibility to T2DM and its vascular complications is yet to be explored. Therefore, in this study, we have employed a computational approach to identify the most damaging missense or nonsynonymous SNPs (nsSNPs) in Glo-1 gene.
View Article and Find Full Text PDFThe CTLA4 receptor is an immune checkpoint involved in the downregulation of T cells. Polymorphisms in this gene have been found to be associated with different diseases like rheumatoid arthritis, autosomal dominant immune dysregulation syndrome, juvenile idiopathic arthritis and autoimmune Addison's disease. Therefore, the identification of polymorphisms that have an effect on the structure and function of CTLA4 gene is important.
View Article and Find Full Text PDFType 2 diabetes mellitus (T2DM) is a complex metabolic disorder that is characterized by hyperglycemia, insulin resistance, and lack of insulin production. It has been previously reported that has therapeutic potential against many diseases. To investigate the antidiabetic action of , this study aimed to analyze its restorative impact in diabetic mice, in which it was administered in diet.
View Article and Find Full Text PDFEnhancement of glycolysis and glutaminolysis are the two most common modalities associated with metabolic reprogramming in rheumatoid arthritis (RA). This enhancement is concomitant to the upregulation of hexokinase 2 (HK2) and glutaminase 1 (GLS1). Hence, the current study was undertaken to identify potential phytobiological inhibitors against HK2 and GLS1, from , an indigenous ethnomedicinal plant found in Pakistan, using computational analysis.
View Article and Find Full Text PDFType 2 Diabetes Mellitus is one of the most common metabolic disorders, and is characterized by abnormal blood sugar level due to impaired insulin secretion or impaired insulin action-or both. Metformin is the most commonly used drug for the treatment of Type 2 Diabetes Mellitus, but due to its slow mode of action and various side effects it shows poor and slow therapeutic response in patients. Currently, scientists are trying to tackle these limitations by developing nanomedicine.
View Article and Find Full Text PDFRheumatoid arthritis is an autoimmune disorder of complex disease etiology. Currently available serological diagnostic markers lack in terms of sensitivity and specificity and thus additional biomarkers are warranted for early disease diagnosis and management. We aimed to screen and compare serum proteome profiles of rheumatoid arthritis serotypes with healthy controls in the Pakistani population for identification of potential disease biomarkers.
View Article and Find Full Text PDFRheumatoid arthritis (RA) is a common chronic inflammation-mediated disorder having systematic complications. RA triggers a self-directed inflammatory and immunological cascade that culminates in joint destruction. Though a range of treatment options are available, none of them are without adverse effects and this has led researchers to search for alternative solutions.
View Article and Find Full Text PDFType 2 diabetes mellitus and breast cancer are complex, chronic, heterogeneous, and multi-factorial diseases; with common risk factors including but not limited to diet, obesity, and age. They also share mutually inclusive phenotypic features such as the metabolic deregulations resulting from hyperglycemia, hypoxic conditions and hormonal imbalances. Although, the association between diabetes and cancer has long been speculated; however, the exact molecular nature of this link remains to be fully elucidated.
View Article and Find Full Text PDFNon-synonymous missense SNPs (nsSNPs) in CPE and GNAS genes were investigated computationally. In silico identified nsSNPs were experimentally validated in type II diabetes mellitus (T2DM) in Pakistani Pathan population using next generation sequencing (NGS). Sixty two high-risk nsSNPs in CPE and 44 in GNAS were identified.
View Article and Find Full Text PDFHypoxia inducible factor-1 is a heterodimeric transcription factor that regulates cellular responses to hypoxia and is involved in tumor progression and resistance to chemotherapy. Dimerization between HIF-1α and β subunits has been recognized crucial for DNA binding and transcriptional activity of HIF-1. Therefore, inhibitors of α and β dimerization subunits of HIF-1 may potentially evade HIF-1-mediated chemotherapy resistance.
View Article and Find Full Text PDFRheumatoid Arthritis is an inflammatory disease primarily involves the inflamed synovium, affecting about 0.5-1 % population worldwide. It is the assumption from many years that oxidative stress is involved in the pathophysiology of inflammatory disorders like RA and many others.
View Article and Find Full Text PDFGenome-wide association studies (GWAS) have identified multiple type 2 diabetes (T2D) loci, mostly among populations of European descent. There is a high prevalence of T2D among Pakistanis. Both genetic and environmental factors may be responsible for this high prevalence.
View Article and Find Full Text PDFObjective: Copy number variation (CNV) is a structural variation in the human genome that has been associated with multiple clinical phenotypes. B cells are important components of rheumatoid arthritis- (RA-) mediated immune response; hence, CNV in the regulators of B cells (such as VPREB1) can influence RA susceptibility. In this study, we aimed to explore the association of CNV in the gene with RA susceptibility in the Pakistani population.
View Article and Find Full Text PDFRheumatoid arthritis (RA) is a multifactorial autoimmune disease. The interaction of genetic and environmental factors is likely necessary for RA. Among potential genetic factors, many major histocompatibility complex (MHC) and non-MHC variants may be involved in RA susceptibility.
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