The animal study was reviewed and approved by The University of Michigan’s Institutional Animal Care and Use Committee approved all animal protocols .SE, RH, and EF designed the studies. IW-D, ST, and BM performed the immunophenotyping. BK, JH, FM, IW-D, ST, RH, and SE contributed to the tissue processing. BK and SE performed theinsulin stimulation and western blotting. IW-D sectioned and stained the images for microglial morphology. SE and RH imaged and analyzed the microglial morphology data.
Authors are grateful to the University of Michigan flow cytometry core and Rogel Cancer Center immunology core for assistance with flow cytometry and ELISA, as well as the University of Michigan Unit for Laboratory Animal Medicine for their care of the animals used for this work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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New insights of minimum requirement on legumes (Fabaceae sp.) daily intake in Malaysia - BMC NutritionBackground Despite their low energy density and high nutrient content, legumes may be under-recognised as a beneficial food for the prevention and management of obesity and related diseases, such as cardiovascular disease (CVD). This study aims to analyse the moderation effect of legume intake on the relationship between BMI and the prevalence of CVD among the Malaysian adult population. Methods This study addressed communities of urban and rural Malaysia, including adults aged between 35 and 70 years old at the baseline recruitment. A series of standardised questionnaires were used to assess legume intake, history of comorbidities and socio-demographic information. Resting blood pressure measurements and physical examinations were performed to collect blood pressure and anthropometric data. Bivariate analysis was completed to determine the association between legume intake, socio-demographic characteristics and CVD prevalence. Moderation analysis was used to quantify the moderation effect of minimum daily legume intake on the relationship between BMI and CVD prevalence. Results This study found that those who consume less than 3 servings of legumes per day benefit from protective effects against CVD risk (POR = 0.56, 95% CI = 0.37 – 0.85). Moderation analysis of a minimum of three servings/day for the relationship between BMI and CVD prevalence showed significant effects. The group that benefited the most from this effect was those with a BMI in the range of 26 to 34 kg/m2. Conclusions This study provides new insights into the recommendation for legume intake according to the relationship between BMI and the prevalence of CVD in Malaysian adults. This study recommends that those with a BMI of 26 to 34 kg/m2 should consume at least 3 servings of legumes per day to reduce the risk of CVD. Further prospective research is warranted to affirm these findings throughout the Malaysian population.
Source: BioMedCentral - 🏆 22. / 71 Read more »
Efficient preclinical treatment of cortical T cell acute lymphoblastic leukemia with T lymphocytes secreting anti-CD1a T cell engagersBackground The dismal clinical outcome of relapsed/refractory (R/R) T cell acute lymphoblastic leukemia (T-ALL) highlights the need for innovative targeted therapies. Although chimeric antigen receptor (CAR)-engineered T cells have revolutionized the treatment of B cell malignancies, their clinical implementation in T-ALL is in its infancy. CD1a represents a safe target for cortical T-ALL (coT-ALL) patients, and fratricide-resistant CD1a-directed CAR T cells have been preclinically validated as an immunotherapeutic strategy for R/R coT-ALL. Nonetheless, T-ALL relapses are commonly very aggressive and hyperleukocytic, posing a challenge to recover sufficient non-leukemic effector T cells from leukapheresis in R/R T-ALL patients. Methods We carried out a comprehensive study using robust in vitro and in vivo assays comparing the efficacy of engineered T cells either expressing a second-generation CD1a-CAR or secreting CD1a x CD3 T cell-engaging Antibodies (CD1a-STAb). Results We show that CD1a-T cell engagers bind to cell surface expressed CD1a and CD3 and induce specific T cell activation. Recruitment of bystander T cells endows CD1a-STAbs with an enhanced in vitro cytotoxicity than CD1a-CAR T cells at lower effector:target ratios. CD1a-STAb T cells are as effective as CD1a-CAR T cells in cutting-edge in vivo T-ALL patient-derived xenograft models. Conclusions Our data suggest that CD1a-STAb T cells could be an alternative to CD1a-CAR T cells in coT-ALL patients with aggressive and hyperleukocytic relapses with limited numbers of non-leukemic effector T cells. Data are available on reasonable request.
Source: medical_xpress - 🏆 101. / 51 Read more »
Presentation of SLE after COVID vaccination in a pediatric patient - BMC RheumatologyBackground The outbreak of severe acute respiratory syndrome coronavirus 2 has had an enormous impact on global health. Vaccination remains one of the most effective interventions for disease prevention. Clinically significant vaccine side effects are uncommon, though autoimmune-mediated disease occurs in a small percentage of vaccine recipients. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that is associated with significant morbidity and mortality. Childhood-onset SLE tends to have more severe disease manifestations than adult-onset SLE. In adults, there are a few reported cases of SLE developing soon after coronavirus disease 2019 (COVID-19) mRNA vaccination. Case presentation A 14-year-old previously healthy male developed laboratory and clinical evidence of SLE, including maculopapular malar rash, arthritis, pleuritic chest pain, and class V (membranous) lupus nephritis, 2 days after his third dose of the Pfizer-BioNTech COVID-19 vaccine. The patient’s symptoms improved after initiation of prednisone and mycophenolate mofetil. We also summarize eleven prior case reports describing SLE after COVID-19 vaccine in adults. Conclusion To our knowledge, this is the first reported pediatric patient with new onset SLE following COVID-19 mRNA vaccination. While potential mechanistic links exist between COVID-19 vaccination and SLE development, additional studies are necessary to elucidate the exact nature of this relationship.
Source: BioMedCentral - 🏆 22. / 71 Read more »