Daltonwalton8077
Purpose To compare serum total calcium and phosphate levels in patients with non-severe COVID-19 with age, sex, and serum 25-hydroxyvitamin D level matched healthy adult cohort. Methods In this retrospective case-control study, medical records of patients (≥18 years) diagnosed as non-severe COVID-19 admitted at and discharged from our tertiary care institution during the period from April 10, 2020 and June 20, 2020 were retrieved. Baseline investigations, notably, serum calcium, phosphate, albumin, magnesium, 25-hydroxyvitamin D, and C-reactive protein (CRP), were performed at admission before any form of calcium or vitamin D supplementation were considered. The biochemical parameters were compared with age, sex, and 25-hydroxyvitamin D matched healthy adult controls (11 ratio) derived from the Chandigarh Urban Bone Epidemiological Study (CUBES). Results After exclusion, 72 patients with non-severe COVID-19 (63 mild and 9 moderate disease) and an equal number of healthy controls were included in the final analysis. Age, sex, serum 25-hydroxyvitamin D, and albumin levels were matched between the 2 groups. Hypovitaminosis D and hypocalcemia were seen in 97 and 67% of the patients, respectively. The patients had lower serum calcium (P value less then 0.001) and phosphate (P = 0.007) compared with the controls. There was no statistically significant correlation between serum calcium and CRP. Conclusions Hypocalcemia is highly prevalent even in COVID-19 patients with non-severe disease probably implying that hypocalcemia is intrinsic to the disease. Prospective studies with larger number of patients are required to prove this hypothesis and unravel the underlying pathophysiological mechanisms.As the primary surge of coronavirus disease 2019 (COVID-19) wanes in many countries, it is important to reconsider best practice. More cases, probably the majority of cases, are yet to come. Hopefully, during this next phase, we will have more time, more resources, and more experience from which to affect better outcomes. Here, we examine the compromised oxygen strategy that many nations followed. We explore the evidence related to such strategies and discuss the potential mortality impact of delaying oxygen treatment in COVID-19 pneumonia.Background The association between aspirin use and the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) or hepatitis C (HCV) virus infection remains not fully determined. KPT185 A meta-analysis was performed to summarize the findings of cohort studies. Methods Relevant cohort studies were retrieved via a search of PubMed Cochrane's Library and Embase databases. A random-effect model was used to pool the results. Subgroup analyses were performed to evaluate the influence of study characteristics on the association. Results Seven cohort studies with 120,945 adult patients with HBV or HCV infection were included. Pooled results showed that aspirin use was independently associated with a reduced risk of HCC in these patients (risk ratio 0.73, 95% confidence interval 0.64 to 0.83, p less then 0.001; I2 = 86%). Subgroup analyses showed that aspirin use was associated with a reduced HCC risk regardless of the viral type, age, sex, the diabetic, and cirrhotic status of the patients, and the follow-up durations. Moreover, consistent results were obtained in studies with and without adjustment of antiviral treatment and statin use. Pooled results of four studies showed that aspirin use was associated with an increased risk of gastrointestinal bleeding in these patients (risk ratio 1.15, 95% confidence interval 1.02 to 1.28, p = 0.02; I2 = 0%). Conclusions Aspirin use was independently associated with a reduced risk of HCC in patients with HBV or HCV infection, whereas the risk of gastrointestinal bleeding may be increased. These results should be validated in clinical trials.HLA-B27 has an established relationship with the development of ankylosing spondylitis (AS). After reviewing the HLA-B genotype from 407 Chinese subjects (318 patients and 89 sex-matched controls), we found that 252 patients and 32 controls were HLA-B27(+) and that HLA-B*2704 was the dominant HLA-B27 subtype (N = 224). In all participants, HLA*2704 homozygous were only detected in two patients. In the HLA-B27(+) group, HLA-B40 was observed in 51 cases and one control (p less then 0.05, OR = 7.87, 95% CI 1.05-59.0); of these, the most genotype was HLA-B*2704/B*4001(N = 38). Two hundred thirty-nine patients' clinical information was recorded. Cases with HLA-B27/B46 had more peripheral joint involvement (OR = 3.95, 95% CI 1.77-8.79) in HLA-B27(+) AS. HLA-B*1502 may be a significant risk element to peripheral joint involvement (p less then 0.05) in HLA-B27(-) patients. Therefore, we believe HLA-B*4001, HLA-B*4601, and HLA-B*1502 can be the test indicators for AS diagnostic value.Skin cutaneous melanoma (SKCM) is the major cause of death for skin cancer patients, its high metastasis often leads to poor prognosis of patients with malignant melanoma. However, the molecular mechanisms underlying metastatic melanoma remain to be elucidated. In this study we aim to identify and validate prognostic biomarkers associated with metastatic melanoma. We first construct a co-expression network using large-scale public gene expression profiles from GEO, from which candidate genes are screened out using weighted gene co-expression network analysis (WGCNA). A total of eight modules are established via the average linkage hierarchical clustering, and 111 hub genes are identified from the clinically significant modules. Next, two other datasets from GEO and TCGA are used for further screening of biomarker genes related to prognosis of metastatic melanoma, and identified 11 key genes via survival analysis. We find that IL10RA has the highest correlation with clinically important modules among all identified biomarker genes. Further in vitro biochemical experiments, including CCK8 assays, wound-healing assays and transwell assays, have verified that IL10RA can significantly inhibit the proliferation, migration and invasion of melanoma cells. Furthermore, gene set enrichment analysis shows that PI3K-AKT signaling pathway is significantly enriched in metastatic melanoma with highly expressed IL10RA, indicating that IL10RA mediates in metastatic melanoma via PI3K-AKT pathway.[This corrects the article DOI 10.3389/fcell.2020.00753.].Vertebrate genomes are marked by notably high levels of 5-cytosine DNA methylation (5meC). The clearest function of DNA methylation among members of the subphylum is repression of potentially deleterious transposable elements (TEs). However, enrichment in the bodies of protein coding genes and pericentromeric heterochromatin indicate an important role for 5meC in those genomic compartments as well. Moreover, DNA methylation plays an important role in silencing of germline-specific genes. Impaired function of major components of DNA methylation machinery results in lethality in fish, amphibians and mammals. Despite such apparent importance, mammals exhibit a dramatic loss and regain of DNA methylation in early embryogenesis prior to implantation, and then again in the cells specified for the germline. In this minireview we will highlight recent studies that shine light on two major aspects of embryonic DNA methylation reprogramming (1) The mechanism of DNA methylation loss after fertilization and (2) the protection of discrete loci from ectopic DNA methylation deposition during reestablishment. Finally, we will conclude with some extrapolations for the evolutionary underpinnings of such extraordinary events that seemingly put the genome under unnecessary risk during a particularly vulnerable window of development.
Cryptophthalmos is characterized by congenital ocular dysplasia with eyelid malformation. The pathogenicity of mutations in genes encoding components of the FRAS1/FREM protein complex is well established, but the underlying pathomechanisms of this disease are still unclear. In the previous study, we generated mice carrying
compound heterozygous mutations using CRISPR/Cas9 and showed that these mice recapitulated the human cryptophthalmos phenotype.
In this study, we tracked changes in the metabolic profile of embryos and expression of metabolism-related genes in
mutant mice on E13.5 compared with wild-type mice. RNA sequencing (RNA-seq) was utilized to decipher the differentiated expression of genes associated with metabolism. Untargeted metabolomics and targeted metabolomics analyses were performed to detect and verify the shifts in the composition of the embryonic metabolome.
Differentially expressed genes participating in amino acid metabolism and energy metabolism were observed by RNA-seq. Tthe pathogenesis of cryptophthalmos.
We demonstrate that Frem2 mutant fetal mice have increased susceptibility to the disruption of eye morphogenesis in association with distinct transcriptomic and metabolomic signatures. Our findings suggest that the metabolomic signature established before birth may play a role in mediating cryptophthalmos in Frem2 mutant mice, which may have important implications for the pathogenesis of cryptophthalmos.Bone regeneration is the ultimate goal of periodontal therapies, in which osteogenic differentiation of human periodontal ligament stem cells plays a critical role. The tripartite motif (TRIM)16, an E3 ubiquitin ligase, is downregulated in periodontal tissues of patients with periodontitis, while the role of TRIM16 in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) is largely unknown. Firstly, we found that TRIM16 was increased throughout the osteogenic media induced differentiation of hPDLSCs. Then overexpression plasmids and specific short-hairpin RNAs (shRNAs) were constructed to manipulate the expression of target molecules. TRIM16 significantly promoted alkaline phosphatase activity, mineralized nodule formation, and positively regulated the expression of osteo-specific markers RUNX2, COL1A1 and OCN except the mRNA of RUNX2. Mechanistically, TRIM16 serves as a pivotal factor that stabilizes RUNX2 protein levels by decreasing CHIP-mediated K48-linked ubiquitination degradation of the RUNX2 protein. This study identified a novel mechanism of TRIM16 in regulating stability of the RUNX2 protein, which promoted the osteogenic differentiation of hPDLSCs. TRIM16 may be a potential target of stem cell based-bone regeneration for periodontal therapies.
CircRNAs recently have shown critical roles in tumor biology. However, their roles in prostate cancer (PCa) remains largely unclear.
CircRNA microarrays were performed in immortal prostate cell line RWPE1 and PCa cell lines as DU145, PC3, LNCaP, C4-2, and 22RV1. Combined with upregulated circRNAs in PCa tissues, circNOLC1 expression was validated in PCa cells and tissues
qRT-PCR and FISH. Sanger sequencing, actinomycin D, gDNA, and cDNA, RNase R assays were used to assess the circular characteristics of circNOLC1. CCK-8, colony formation, transwell migration assays, and mice xenograft models were conducted to evaluate the functions of PCa cells after circNOLC1 knockdown and overexpression. RNA pulldown, luciferase reporter assay, FISH (fluorescence
hybridization), and CHIP were utilized to illustrate the further mechanisms of circNOLC1.
Our research indicated that circNOLC1 was overexpressed in PCa cells and tissues, and circNOLC1 was more stable than linear NOLC1 mRNA. CircNOLC1 promoted PCa cells proliferation and migration
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