Osteoarthritis: insights into pathogenesis and futuristic treatment strategies

Osteoarthritis is the most common musculoskeletal condition world over that causes significant health, economic, and societal burdens. Till date, no therapeutic approaches have been able to stop or delay the progression of osteoarthritis satisfactorily. Structural and clinical features of the disease are characterized by a high inter-patient variability. This heterogeneity is believed to be a major factor associated with the complexity of osteoarthritis and the on-going difficulty to identify a single therapy for all sub-groups. The objective of this review is to highlight recent advances in the understanding of the pathophysiology of osteoarthritis and latest biological treatments available, their limitations and to bring to notice the latest state-of-the-art on-going research on novel therapies. For this study we searched different online databases such as PubMed and Cochrane Library from inception to January 2022. We identified eligible studies on the pathophysiologic findings, prevalence, or incidence of knee osteoarthritis, available treatments, and current research for future therapies. Besides the availability of vast literature on cartilage extracellular matrix and its changes in osteoarthritis, the complicated mechanism of the disease still has missing links in the chain. Presently, biological treatments such as platelet rich plasma, bone marrow mesenchymal stem cells and autologous fragmented adipose tissue containing structural vascular fraction are commonly used. In future, gene therapy could become a potential option for treating the disease. More extensive insights into the pathophysiology of osteoarthritis will be helpful in designing therapies that can curb structural progression and promote cartilage regeneration thus providing more potent relief from painful and disabling condition associated with osteoarthritis

Ewing sarcoma genomics and recent therapeutic advancements

Ewing sarcomas are highly heterogenous mesenchymal tumors that develop in bone or soft tissue and primarily affect children, teenagers, and young adults. After osteosarcoma, it is the second most common malignant bone sarcoma. Ewing sarcoma, metastatic and relapsed, typically have a poor prognosis and recurrences are frequent, leading to high rates of morbidity and mortality. The ongoing inability to increase overall survival for patients with ewing sarcoma emphasizes the critical requirement for the quick translation of emerging therapy approaches. Targeting the EWR1/FLI1 fusion protein, which is the primary genetic anomaly and master regulator of ewing sarcoma and found in 80–90% of instances of ewing tumors, is the most crucial objective. This review offers new insights into the genomics and proteomics of ewing sarcoma signaling and how it influences the tumor microenvironment and disease progression. It also elucidates how recent technological advancements have explained some of the underlying oncogenic characteristics of ewing sarcoma. The current review examined existing and potential experimental therapies that, by enhancing patient survival and quality of life, target multiple signaling pathways involved in the progression of ewing sarcoma. These therapies may one day replace current regimens as the new standard of care for patients

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Not AvailableThe present study was conducted to identify the differentially expressed miRNAs (DE miRNAs) in the peripheral blood mononuclear cells of crossbred pigs in response to CSF vaccination on 7 and 21 days of post vaccination as compared to unvaccinated control (0 dpv). Simultaneously, set of miRNA was predicted using mRNA seq data at same time point. The proportion of CD4(-)CD8( + ) and CD4( + )CD8( + ) increased after vaccination, and the mean percentage inhibition was 86.89% at 21 dpv. It was observed that 22 miRNAs were commonly expressed on both the time points. Out of predicted DE miRNAs, it was found that 40 and 35 DE miRNAs were common, obtained from miRNA seq analysis and predicted using mRNA seq data on 7 dpv versus 0 dpv and 21 dpv versus 0 dpv respectively. Two DE miRNAs, ssc-miR-22-5p and ssc-miR-27b-5p, were selected based on their log(2) fold change and functions of their target genes in immune process/pathway of viral infections. The validations of DE miRNAs using qRT-PCR were in concordance with miRNA seq analysis. Two set of target genes, CD40 and SWAP70 (target gene of ssc-miR-22-5p) and TLR4 and Lyn (target gene of ssc-miR-27b-5p), were validated and were in concordance with results of RNA seq analysis at a particular time point (except TLR4). The first report of genome-wide identification of differentially expressed miRNA in response to live attenuated vaccine virus of classical swine fever revealed miR-22-5p and miR-27b-5p were differentially expressed at 7 dpv and 21 dpv.CABIN project of IASRI; SubDIC (BTISnet), ICAR-IVR