RORA

The circadian rhythm regulates many crucial physiological processes, impacting human aging and aging-related outcomes. Observational evidence links circadian rhythm disturbance to PM2.5 exposure, yet the underlying DNA methylation mechanisms remain unclear due to limited PM2.5 -dominated experimental settings. Therefore, we investigated the associations between short-term PM2.5 exposure and DNA methylation changes of 1188 CpG candidates across circadian genes among 32 young adults in the FDU study, with the validation in 26 individuals from the PKU study...

Bovine coronavirus (BCoV) infection causes significant economic loss to the dairy and beef industries worldwide. BCoV exhibits dual tropism, infecting the respiratory and enteric tracts of cattle. The enteric BCoV isolates could also induce respiratory manifestations under certain circumstances. However, the mechanism of this dual tropism of BCoV infection has not yet been studied well. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a dual role in virus infection, mediating virus or modulating host immune regulatory genes through complex virus-host cell interactions...

Gene regulatory elements, such as enhancers, greatly influence cell identity by tuning the transcriptional activity of specific cell types. Dynamics of enhancer landscape during early human Th17 cell differentiation remains incompletely understood. Leveraging ATAC-seq-based profiling of chromatin accessibility and comprehensive analysis of key histone marks, we identified a repertoire of potential enhancers that potentially exert control over the fate specification of Th17 cells. We found 23 SNPs associated with autoimmune diseases within Th17-enhancers that precisely overlapped with the binding sites of transcription factors actively engaged in T-cell functions...

Depressive disorders have increased in global prevalence, making improved management of these disorders a public health priority. Prior research has linked circadian clock genes to depression, either through direct interactions with mood-related pathways in the brain or by modulating the phase of circadian rhythms. Using machine learning and statistical techniques, we explored associations between 157,347 SNP variants from 51 circadian-related genes and depression scores from the patient health questionnaire 9 (PHQ-9) in 99,939 UK Biobank participants...

Degeneration of the macula is associated with several overlapping diseases including age-related macular degeneration (AMD) and Stargardt Disease (STGD). Mutations in ATP Binding Cassette Subfamily A Member 4 (ABCA4) are associated with late-onset dry AMD and early-onset STGD. Additionally, both forms of macular degeneration exhibit deposition of subretinal material and photoreceptor degeneration. Retinoic acid related orphan receptor α (RORA) regulates the AMD inflammation pathway that includes ABCA4, CD59, C3 and C5...

Circadian clock perturbation frequently occurs in cancer and facilitates tumor progression by regulating malignant growth and shaping the immune microenvironment. Emerging evidence has indicated that clock genes are disrupted in melanoma and linked to immune escape. Here, we found that the expression of retinoic acid receptor-related orphan receptor-α (RORA) is downregulated in melanoma patients and that patients with higher RORA expression have a better prognosis after immunotherapy. Additionally, RORA was significantly positively correlated with T-cell infiltration and recruitment...

BACKGROUND: Laparoscopic sacrocolpopexy (LSC) and robot-assisted sacrocolpopexy (RSC) using mesh are popular approaches for treating pelvic organ prolapse (POP). However, it is not uncommon that native tissue repair (NTR) should be presented as an option to patients who are expected to have extensive intraperitoneal adhesion or patients for whom LSC or RSC is difficult owing to various risk factors. Laparoscopic vaginal stump-uterosacral ligament fixation (Shull method) has been introduced as a method for NTR in case of POP...

PURPOSE: To longitudinally assess the impact of high-risk structural biomarkers for natural disease progression in non-exudative age-related macular degeneration (AMD) on spatially resolved mesopic and scotopic fundus-controlled perimetry testing. METHODS: Multimodal retinal imaging data and fundus-controlled perimetry stimuli points were semiautomatically registered according to landmark correspondences at each annual visit over a period of up to 4 years. The presence of sub-RPE drusen, subretinal drusenoid deposits, pigment epithelium detachments (PEDs), hyper-reflective foci (HRF), vitelliform lesions, refractile deposits, and incomplete RPE and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA) were graded at each stimulus position and visit...

Kaposi's sarcoma (KS) is the second most common tumor in human immunodeficiency virus (HIV) infected patients worldwide. While many miRNAs have been confirmed to be involved in KS biological processes, no relevant studies have combined miRNA and mRNA expression profiles using KS patient tissue biopsies. In this study, we performed transcriptome sequencing on tumor and normal tissues from four KS patients and identified differentially expressed mRNA and miRNA, further performed target gene prediction and enrichment analysis...

Musk secreted by male forest musk deer (Moschus berezovskii) musk glands is an invaluable component of medicine and perfume. Musk secretion depends on musk gland maturation; however, the mechanism of its development remains elusive. Herein, using single cell multiome ATAC + gene expression coupled with several bioinformatic analyses, a dynamic transcriptional cell atlas of musk gland development was revealed, and key genes and transcription factors affecting its development were determined. Twelve cell types, including two different types of acinar cells (Clusters 0 and 10) were identified...

OBJECTIVE: Sepsis is linked to high morbidity and mortality rates. Consequently, early diagnosis is crucial for proper treatment, reducing hospitalization, and mortality rates. Additionally, over one-fifth of sepsis patients still face a risk of death. Hence, early diagnosis, and effective treatment play pivotal roles in enhancing the prognosis of patients with sepsis. METHOD: The study analyzed whole blood data obtained from patients with sepsis and control samples sourced from three datasets (GSE57065, GSE69528, and GSE28750)...

INTRODUCTION: The close association between cuproptosis and tumor immunity in triple-negative breast cancer (TNBC) allows its monitoring for predicting the prognosis of patients with TNBC. Nevertheless, the biological function and prognostic value of cuproptosis-related miRNAs and their target genes have not been reported. PURPOSE: To construct the miRNA and mRNA-based risk models associated with cuproptosis for patients with TNBC. METHODS: Comparison of expression levels for genes associated with cuproptosis was executed between patients in the normal individuals and the TCGA-TNBC cohort...

Fuchs endothelial corneal dystrophy (FECD) is a leading indication for corneal transplantation, but its molecular etiology remains poorly understood. We performed genome-wide association studies (GWAS) of FECD in the Million Veteran Program followed by multi-ancestry meta-analysis with the previous largest FECD GWAS, for a total of 3970 cases and 333,794 controls. We confirm the previous four loci, and identify eight novel loci: SSBP3, THSD7A, LAMB1, PIDD1, RORA, HS3ST3B1, LAMA5, and COL18A1. We further confirm the TCF4 locus in GWAS for admixed African and Hispanic/Latino ancestries and show an enrichment of European-ancestry haplotypes at TCF4 in FECD cases...

RORα is a transcription factor encoded by RORA gene. This protein is involved in several metabolic conditions, including obesity. We assessed association between two polymorphisms within this gene (namely rs11639084 and rs4774388) and severe obesity in Iranian population. Both SNPs were associated with obesity in all models (P < 0.0001) except for over-dominant model. T allele of rs11639084 was associated with this trait with OR (95% CI) of 16.85 (13.11-21.67) and was considered as the risk allele...

The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma (LUAD), and chemoresistance, however, usually results in treatment failure and limits its application in the clinic. It has been shown that microRNAs (miRNAs) play a significant role in tumor chemoresistance. In this study, miR-125b was identified as a specific cisplatin (DDP)-resistant gene in LUAD, as indicated by the bioinformatics analysis and the real-time quantitative PCR assay. The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time...

The chemotherapeutic agent tegafur, a prodrug that prolongs the half-life of fluorouracil (5-FU), exerts antitumor effects against various cancers. Since tegafur is metabolized to 5-FU by CYP2A6 in the liver, the expression of CYP2A6 determines the effect of tegafur. Here, we report that the expression rhythm of Cyp2a5, a homolog of human CYP2A6, in female mice causes dosing time-dependent differences in tegafur metabolism. In the livers of female mice, CYP2A5 expression showed a circadian rhythm, peaking during the dark period...

BACKGROUND: Microwave endometrial ablation (MEA) is a minimally invasive treatment method for heavy menstrual bleeding. However, additional treatment is often required after recurrence of uterine myomas treated with MEA. Additionally, because this treatment ablates the endometrium, it is not indicated for patients planning to become pregnant. To overcome these issues, we devised a method for ultrasound-guided microwave ablation of uterine myoma feeder vessels. We report three patients successfully treated for heavy menstrual bleeding, secondary to uterine myoma, using our novel method...

Psychosis occurs inside the brain, but may have external manifestations (peripheral molecular biomarkers, behaviors) that can be objectively and quantitatively measured. Blood biomarkers that track core psychotic manifestations such as hallucinations and delusions could provide a window into the biology of psychosis, as well as help with diagnosis and treatment. We endeavored to identify objective blood gene expression biomarkers for hallucinations and delusions, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design...

BACKGROUND: Age and obesity are dominant risk factors for several common cardiometabolic disorders, and both are known to impair adipose tissue function. However, the underlying cellular and genetic factors linking aging and obesity on adipose tissue function have remained elusive. Adipose stem and precursor cells (ASPCs) are an understudied, yet crucial adipose cell type due to their deterministic adipocyte differentiation potential, which impacts the capacity to store fat in a metabolically healthy manner...

BACKGROUND: Renal transplantation plays an essential role in the quality of life of patients with end-stage renal disease. At least 12% of the renal patients receiving transplantations show graft rejection. One of the methods used to diagnose renal transplantation rejection is renal allograft biopsy. This procedure is associated with some risks such as bleeding and arteriovenous fistula formation. In this study, we applied a bioinformatics approach to identify serum markers for graft rejection in patients receiving a renal transplantation...