Notes

Intense renal injuries linked to rhabdomyolysis inside a affected individual along with COVID-19.
We also discuss the problems and perspectives of the two disciplines and how to integrate their conceptual frameworks to address basic equations in biology in a new, innovative way.Recent advances in next-generation sequencing (NGS) technologies have triggered the rapid accumulation of publicly available multi-omics datasets. The application of integrated omics to explore robust signatures for clinical translation is increasingly emphasized, and this is attributed to the clinical success of immune checkpoint blockades in diverse malignancies. However, effective tools for comprehensively interpreting multi-omics data are still warranted to provide increased granularity into the intrinsic mechanism of oncogenesis and immunotherapeutic sensitivity. Therefore, we developed a computational tool for effective Immuno-Oncology Biological Research (IOBR), providing a comprehensive investigation of the estimation of reported or user-built signatures, TME deconvolution, and signature construction based on multi-omics data. Notably, IOBR offers batch analyses of these signatures and their correlations with clinical phenotypes, long non-coding RNA (lncRNA) profiling, genomic characteristics, and signatures generated from single-cell RNA sequencing (scRNA-seq) data in different cancer settings. Additionally, IOBR integrates multiple existing microenvironmental deconvolution methodologies and signature construction tools for convenient comparison and selection. Collectively, IOBR is a user-friendly tool for leveraging multi-omics data to facilitate immuno-oncology exploration and to unveil tumor-immune interactions and accelerating precision immunotherapy.Osteoporosis is the most prevalent metabolic bone disease that affects half the women in the sixth and seventh decade of life. Osteoporosis is characterized by uncoupled bone resorption that leads to low bone mass, compromised microarchitecture and structural deterioration that increases the likelihood of fracture with minimal trauma, known as fragility fractures. Several factors contribute to osteoporosis in men and women. In women, menopause - the cessation of ovarian function, is one of the leading causes of primary osteoporosis. Over the past three decades there has been growing appreciation that the adaptive immune system plays a fundamental role in the development of postmenopausal osteoporosis, both in humans and in mouse models. In this review, we highlight recent data on the interactions between T cells and the skeletal system in the context of postmenopausal osteoporosis. Finally, we review recent studies on the interventions to ameliorate osteoporosis.Bruton´s tyrosine kinase (BTK) inhibitor (BTKi)s block the B-cell receptor (BCR) signaling cascade by binding to the BTK enzyme preventing the proliferation and survival of malignant and normal B cells. During the past decade, the clinical use of BTKis for the treatment of B-cell malignancies has exponentially grown, changing the treatment landscape for chronic lymphocytic leukemia (CLL) in particular. At present, three different covalent BTKis, ibrutinib, acalabrutinib and zanubrutinib, are FDA-approved and many new inhibitors are under development. Despite having remarkable selectivity for BTK, the first-in-class BTKi ibrutinib can also bind, with various affinities, to other kinases. The combined inhibition of BTK ("on-target" effect) and other kinases ("off-target" effect) can have additive or synergistic anti-tumor effects but also induce undesired side effects which might be treatment-limiting. Such "off-target" effects are expected to be more limited for second-generation BTKis. Moreover, the blockade of BCR signaling also indirectly affects the tumor microenvironment in CLL. Treatment with BTKis potentially impacts on both innate and adaptive immunity. Whether this affects infection susceptibility and vaccination efficacy requires further investigation. Here, we summarize the available knowledge on the impact of BTKis on the immune system and discuss the possible clinical implications. Indeed, a deeper knowledge on this topic could guide clinicians in the management and prevention of infections in patients with CLL treated with BTKis.Disease-associated, high-affinity pathological autoantibody production is a well-described consequence of immune dysregulation affecting B cells in systemic sclerosis (SSc), including the distribution of B-cell subsets. Selleck AK 7 We have previously shown that the increased relative frequency of CD19+CD27+IgD- switched memory B cells is associated with the severe form of SSc. This study sought to analyze memory B cell subsets using an extended range of markers for further subdivision based on CD19, IgD, CD27, CD38 and CD95 phenotype, to define relationship between the alterations of memory B cell subsets and the clinical features of SSc. Peripheral blood samples were obtained from 21 SSc patients, including 14 diffuse (dcSSc) and 7 limited (lcSSc) cutaneous SSc patients, with disease duration of 2.7 ( ± 1.6) years. After purification of CD19+ B cells, multiparametric flow cytometry was performed and the frequencies of CD19+IgD-CD27-CD38+ double negative (DN) 1, CD19+IgDloCD27+CD38+ unswitched, CD19+IgD-CD27+CD38+CD95- rma cell precursors with anti-topoisomerase I antibody positivity could reflect their contribution to pathological autoantibody production, whereas the decrease of memory precursor DN B cells and the increase of anti-citrate synthase IgG autoantibody may have potential significance in the assessment of disease activity.Immune homeostasis is disturbed during severe viral infections, which can lead to loss of tolerance to self-peptides and result in short- or long-term autoimmunity. Using publicly available transcriptomic datasets, we conducted an in-silico analyses to evaluate the expression levels of 52 autoantigens, known to be associated with 24 autoimmune diseases, during SAR-CoV-2 infection. Seven autoantigens (MPO, PRTN3, PADI4, IFIH1, TRIM21, PTPRN2, and TSHR) were upregulated in whole blood samples. MPO and TSHR were overexpressed in both lung autopsies and whole blood tissue and were associated with more severe COVID-19. Neutrophil activation derived autoantigens (MPO, PRTN3, and PADI4) were prominently increased in blood of both SARS-CoV-1 and SARS-CoV-2 viral infections, while TSHR and PTPRN2 autoantigens were specifically increased in SARS-CoV-2. Using single-cell dataset from peripheral blood mononuclear cells (PBMCs), we observed an upregulation of MPO, PRTN3, and PADI4 autoantigens within the low-density neutrophil subset.
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