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      HLA-G 3’UTR polymorphisms & response to a yoga-based lifestyle intervention in rheumatoid arthritis: A randomized controlled trial

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          Abstract

          Background & objectives:

          Human leucocyte antigen (HLA)-G plays a vital role in immunomodulation in rheumatoid arthritis (RA). The mounting evidence suggests a link between HLA-G gene polymorphisms, disease susceptibility and methotrexate treatment response. Various environmental factors influence the onset and progression of RA and its treatment outcomes. The aim is to identify the treatment response of HLA-G 3’ untranslated region polymorphisms to yoga-based lifestyle intervention (YBLI).

          Methods:

          In this eight-week single-blinded randomized controlled trial (CTRI/2017/05/008589), patients with RA (n=140) were randomized into two groups namely, yoga group or non-yoga group. Baseline genomic DNA was isolated using salting-out method. PCR-based methods were used for genotyping. The levels of soluble (s) HLA-G and disease activity were assessed by ELISA and disease activity score-28–erythrocyte sedimentation rate (DAS28-ESR), respectively, at baseline (day 0) and after eight weeks of intervention.

          Results:

          Low-producing sHLA-G genotypes, i.e. +3142GG and 14 bp ins/ins, showed a significant increase in sHLA-G levels after YBLI. The association analysis between HLA-G polymorphisms and treatment for RA showed no considerable differential treatment remission in either of the groups ( P>0.05). The percentages of improvement were higher in the yoga group as compared to the non-yoga group in both the HLA-G +3142G>C and 14 bp ins/del polymorphisms irrespective of their respective genotypes. No significant association was found between sHLA-G levels and disease activity with respect to genotypes.

          Interpretation & conclusions:

          Yoga intervention results in improvement and reduced severity of RA in patients irrespective of the HLA-G 14 bp ins/del or +3142G>C polymorphisms. YBLI may be used as an adjunct therapy in RA independent of the genotypes.

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          Most cited references28

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          Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies

          Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages: (i) triggering, (ii) maturation, (iii) targeting, and (iv) fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Modern pharmacologic therapies (including conventional, biological, and novel potential small molecule disease-modifying anti-rheumatic drugs) remain the mainstay of RA treatment and there has been significant progress toward achieving disease remission without joint deformity. Despite this, a significant proportion of RA patients do not effectively respond to the current therapies and thus new drugs are urgently required. This review discusses recent advances of our  understanding of RA pathogenesis, disease modifying drugs, and provides perspectives on next generation therapeutics for RA.
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            Yoga for depression: the research evidence.

            Yoga-based interventions may prove to be an attractive option for the treatment of depression. The aim of this study is to systematically review the research evidence on the effectiveness of yoga for this indication. Searches of the major biomedical databases including MEDLINE, EMBASE, ClNAHL, PsycINFO and the Cochrane Library were conducted. Specialist complementary and alternative medicine (CAM) and the IndMED databases were also searched and efforts made to identify unpublished and ongoing research. Searches were conducted between January and June 2004. Relevant research was categorised by study type and appraised. Clinical commentaries were obtained for studies reporting clinical outcomes. Five randomised controlled trials were located, each of which utilised different forms of yoga interventions and in which the severity of the condition ranged from mild to severe. All trials reported positive findings but methodological details such as method of randomisation, compliance and attrition rates were missing. No adverse effects were reported with the exception of fatigue and breathlessness in participants in one study. No language restrictions were imposed on the searches conducted but no searches of databases in languages other than English were included. Overall, the initial indications are of potentially beneficial effects of yoga interventions on depressive disorders. Variation in interventions, severity and reporting of trial methodology suggests that the findings must be interpreted with caution. Several of the interventions may not be feasible in those with reduced or impaired mobility. Nevertheless, further investigation of yoga as a therapeutic intervention is warranted.
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              Relaxation Response Induces Temporal Transcriptome Changes in Energy Metabolism, Insulin Secretion and Inflammatory Pathways

              The relaxation response (RR) is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal) genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS) as top upregulated critical molecules (focus hubs) and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-κB-associated upstream and downstream targets that mitigates stress.
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                Author and article information

                Journal
                Indian J Med Res
                Indian J Med Res
                IJMR
                Indian J Med Res
                The Indian Journal of Medical Research
                Wolters Kluwer - Medknow (India )
                0971-5916
                0975-9174
                February 2022
                30 July 2022
                : 155
                : 2
                : 253-263
                Affiliations
                [1 ] Department of Anatomy, Laboratory for Molecular Reproduction & Genetics, New Delhi, India
                [2 ] Department of Rheumatology, All India Institute of Medical Sciences, New Delhi, India
                Author notes
                For correspondence: Dr Rima Dada, Department of Anatomy, Laboratory for Molecular Reproduction & Genetics, All India Institute of Medical Sciences, New Delhi 110 029, India e-mail: rimadadaaiims20@ 123456gmail.com
                Article
                IJMR-155-253
                10.4103/ijmr.IJMR_3196_20
                9629524
                35946202
                106f2f71-4c84-4c63-be68-0265c79707b0
                Copyright: © 2022 Indian Journal of Medical Research

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 25 July 2020
                Categories
                Original Article

                Medicine
                3’ utr hla-g polymorphism,das28-esr,gene environment interaction,randomized controlled trial,rheumatoid arthritis,soluble hla-g

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