Stress granules are shock absorbers that prevent excessive innate immune responses to dsRNA.

Proper defense against microbial infection depends on the controlled activation of the immune system. This is particularly important for the RIG-I-like receptors (RLRs), which recognize viral dsRNA and initiate antiviral innate immune responses with the potential of triggering systemic inflammation and immunopathology. Here, we show that stress granules (SGs), molecular condensates that form in response to various stresses including viral dsRNA, play key roles in the controlled activation of RLR signaling. Without the SG nucleators G3BP1/2 and UBAP2L, dsRNA triggers excessive inflammation and immune-mediated apoptosis. In addition to exogenous dsRNA, host-derived dsRNA generated in response to ADAR1 deficiency is also controlled by SG biology. Intriguingly, SGs can function beyond immune control by suppressing viral replication independently of the RLR pathway. These observations thus highlight the multi-functional nature of SGs as cellular "shock absorbers" that converge on protecting cell homeostasis by dampening both toxic immune response and viral replication.

Telehealth mindful exercise for people with knee osteoarthritis: A decentralized feasibility randomized controlled trial.

Objective: Negative psychological beliefs like fear avoidance and catastrophizing can interfere with exercise engagement in people with knee osteoarthritis (OA). Mindfulness, when integrated with exercise, could potentially address both psychological and physical impairments. Our objectives were to optimize and assess the feasibility of a novel telehealth, group-based mindful exercise intervention for people with knee OA. Methods: We conducted a decentralized randomized controlled trial where participants (n â€‹= â€‹40) with symptomatic knee OA were randomized into mindful exercise (n â€‹= â€‹21) or exercise-only (n â€‹= â€‹19) groups. Both groups received supervised group-based interventions weekly for 8-weeks via Zoom. Primary outcomes were safety, fidelity, and feasibility of the mindful exercise intervention. Participants completed patient-reported outcomes (PRO) for pain, function, and psychological measures at baseline, week-8, and week-14. Results: Participants were from 21 US states; >90% identified as having White race, 16% were from rural areas, and approximately 40% had an annual income < $50,000. At 8-weeks, mindful exercise and exercise groups had retention rates of 86% (18/21) and 100% (19/19), and attendance was 54% (11.4/21) and 68% (13/19) respectively. There were no adverse events in the mindful exercise group and four in the exercise group related to exacerbation of knee pain. Preliminary findings showed numerically larger improvements in several PROs for the mindful exercise group. Conclusion: An 8-week telehealth, group-based, mindful exercise intervention was safe for people with knee OA. Our decentralized approach was feasible in terms of recruitment and retention. Further refinement is needed to improve intervention attendance and participant diversity.

Promising Therapeutic Approach in Pancreatic Cancer: Metabolism-Related Genes.

Most pancreatic cancers are pancreatic ductal adenocarcinomas. This is an extremely lethal disease with poor prognosis and almost no treatment choices. Considering the profound role of the pancreas in the human body, malfunction of this organ can significantly affect quality of life. Although multiple metabolic pathways are altered in cancer cells, certain metabolic gene signatures may be critical for immunotherapy. The reprogrammed metabolism of glucose, amino acids, and lipids can nourish the tumor microenvironment (TME). Previous studies have also shown that reprogrammed metabolism influences immune responses. Tumor-infiltrating immune cells in the TME can adapt their metabolism to blunt the immune system, leading to immunosuppression and tumor progression. The identification of metabolism-related genes (MRGs) associated with immune reactions in pancreatic cancer may lead to improved treatments. This review highlights the characteristics of MRGs in pancreatic cancer and suggests that enhanced anti-cancer therapies could be used to overcome resistance to immunotherapy.