Cancer is one of the most prevailing, deadly and challenging diseases worldwide. The advancement in technology led to the generation of different types of omics data at each genome level that may potentially improve the current status of cancer patients. These data have tremendous applications in managing cancer effectively with improved outcome in patients. This review summarizes the various computational resources and tools housing several types of omics data related to cancer. Major categorization of resources includes-cancer-associated multiomics data repositories, visualization/analysis tools for omics data, machine learning-based diagnostic, prognostic, and predictive biomarker tools, and data analysis algorithms employing the multiomics data. The review primarily focuses on providing comprehensive information on the open-source multiomics tools and data repositories, owing to their broader applicability, economic-benefit and usability. Sections including the comparative analysis, tools applicability and possible future directions have also been discussed in detail. We hope that this information will significantly benefit the researchers and clinicians, especially those with no sound background in bioinformatics and who lack sufficient data analysis skills to interpret something from the plethora of cancer-specific data generated nowadays.Accumulating evidence shows that intestinal homeostasis is mediated by cross-talk between the nervous system, enteric neurons and immune cells, together forming specialized neuroimmune units at distinct anatomical locations within the gut. In this review, we will particularly discuss how the intrinsic and extrinsic neuronal circuitry regulates macrophage function and phenotype in the gut during homeostasis and aberrant inflammation, such as observed in inflammatory bowel disease (IBD). Furthermore, we will provide an overview of basic and translational IBD research using these neuronal circuits as a novel therapeutic tool. Finally, we will highlight the different challenges ahead to make bioelectronic neuromodulation a standard treatment for intestinal immune-mediated diseases.
Atrial fibrillation (AF) has been associated with intracellular calcium disturbances in human atrial myocytes, but little is known about the potential influence of sex and we here aimed to address this issue.
Alterations in calcium regulatory mechanisms were assessed in human atrial myocytes from patients without AF or with long-standing persistent or permanent AF. Patch-clamp measurements revealed that L-type calcium current (ICa) density was significantly smaller in males with than without AF (-1.15±0.37 vs. -2.06±0.29 pA/pF) but not in females with AF (-1.88±0.40 vs. -2.21±0.0.30 pA/pF). In contrast, transient inward currents (ITi) were more frequent in females with than without AF (1.92±0.36 vs. 1.10±0.19 events/min) but not in males with AF. Moreover, confocal calcium imaging showed that females with AF had more calcium spark sites than those without AF (9.8±1.8 vs. 2.2±1.9 sites/µm2) and sparks were wider (3.0±0.3 vs. 2.2±0.3 µm) and lasted longer (79±6 vs. 55±8 ms), favoring their fusion into calcit confounding effects of concurrent disease, risk factors and treatments revealed differential sex-dependent alterations of the calcium homeostasis in AF. The analysis suggests that suppression of calcium release-induced membrane depolarizations with adenosine receptor antagonists may be efficient in women with AF only while therapies aiming to restore L-type calcium current may be more efficient in males with AF.
Although neuropsychiatric involvement in Systemic Lupus Erythematosus (NPSLE) is one of the most complex and troubling manifestations of the disease, validated outcome instruments to be used as sensitive endpoints in controlled clinical trials are lacking. We set out a systematic literature review (SLR) to identify outcome measurement instruments and domains used to assess NPSLE.
The Preferred Reporting Items for systematic reviews and Meta-analysis (PRISMA) guidelines were used. Articles available in English (1967-2020), listed in PubMed, EMBASE, PsycINFO, Cochrane Library and EULAR outcome measures library were screened. learn more All domains and outcome measurement instruments were characterized according to the OMERACT Filter 2.1, considering core areas (manifestations/abnormalities, life impact, death/lifespan, societal/resource use) and contextual factors.
Of 3,392 abstracts evaluated, 83 studies were included in the SLR (15,974 patients, females 89.9%). Eligible studies included domains and instruments pert instruments to promote clinical research in this field, enhancing comparability across studies.
The secreted and membrane-anchored SCUBE (signal peptide-CUB-EGF domain-containing proteins) gene family composed of 3 members was originally identified from endothelial cells (ECs). We recently showed that membrane SCUBE2 binds vascular endothelial growth factor A (VEGFA) and acts as a co-receptor for VEGF receptor 2 (VEGFR2) to modulate EC migration, proliferation and tube formation during postnatal and tumor angiogenesis. However, whether these SCUBE genes cooperate in modulating VEGF signaling during embryonic vascular development remains unknown.
To further dissect the genetic interactions of these scube genes, transcription activator-like effector nuclease-mediated genome editing was used to generate knockout (KO) alleles of each scube gene. No overt vascular phenotypes were seen in any single scube KO mutants because of compensation by other scube genes during zebrafish development. However, scube1 and scube2 double KO (DKO) severely impaired EC filopodia extensions, migration, and proliferation, thus disrupting proper vascular lumen formation during vasculogenesis and angiogenesis as well as development of the organ-specific intestinal vasculature. Further genetic, biochemical, and molecular analyses revealed that Scube1 and Scube2 might act cooperatively at the cell-surface receptor level to facilitate Vegfa signaling during zebrafish embryonic vascularization.
We showed for the first time that cooperation between scube1 and scube2 is critical for proper regulation of angiogenic cell behaviors and formation of functional vessels during zebrafish embryonic development.
Our studies indicate that targeting SCUBE1 and/or SCUBE2 on modulating VEGF signaling might provide potential therapeutic treatments or VEGF-mediated proliferative pathological vascular diseases.
Our studies indicate that targeting SCUBE1 and/or SCUBE2 on modulating VEGF signaling might provide potential therapeutic treatments or VEGF-mediated proliferative pathological vascular diseases.learn more
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