Goldkjellerup8882

Our observations provide in vivo evidence corroborating the notion that CLU is a potential modulator of metabolic and/or proteostatic pathways playing an important role in diabetes and tumorigenesis.Although DNA methylation variation of autosomal CpGs provides robust age predictive biomarkers, no male-specific age predictor exists based on Y-CpGs yet. Since sex chromosomes play an important role in aging, a Y-chromosome-based age predictor would allow studying male-specific aging effects and would also be useful in forensics. Here, we used blood-based DNA methylation microarray data of 1,057 males from six cohorts aged 15-87 and identified 75 Y-CpGs with an interquartile range of ≥0.1. Of these, 22 and six were significantly hyper- and hypomethylated with age (p(cor) less then 0.05, Bonferroni), respectively. Amongst several machine learning algorithms, a model based on support vector machines with radial kernel performed best in male-specific age prediction. We achieved a mean absolute deviation (MAD) between true and predicted age of 7.54 years (cor=0.81, validation) when using all 75 Y-CpGs, and a MAD of 8.46 years (cor=0.73, validation) based on the most predictive 19 Y-CpGs. The accuracies of both age predictors did not worsen with increased age, in contrast to autosomal CpG-based age predictors that are known to predict age with reduced accuracy in the elderly. Overall, we introduce the first-of-its-kind male-specific epigenetic age predictor for future applications in aging research and forensics.The effect of calorie restriction (CR) on the microbiome, fecal metabolome, and colon transcriptome of adult and old male mice was compared. Life-long CR increased microbial diversity and the Bacteroidetes/Firmicutes ratio and prevented the age-related changes in the microbiota, shifting it to a younger microbial and fecal metabolite profile in both C57BL/6JN and B6D2F1 mice. Old mice fed CR were enriched in the Rikenellaceae, S24-7 and Bacteroides families. The changes in the microbiome that occur with age and CR were initiated in the cecum and further modified in the colon. Short-term CR in adult mice had a minor effect on the microbiome but a major effect on the transcriptome of the colon mucosa. These data suggest that CR has a major impact on the physiological status of the gastrointestinal system, maintaining it in a more youthful state, which in turn could result in a more diverse and youthful microbiome.AlkB family of Fe (II) and α-ketoglutarate-dependent dioxygenases plays essential roles in development of ovarian serous carcinoma (OV). However, the molecular profiles of AlkB family in OV have not been clarified. The results indicated that the expression of ALKBH1/3/5/8 and FTO was lower in OV patients while ALKBH2/4/6/7 expression was higher. There was a strong correlation between ALKBH5/7 and pathological stage of OV patients. Kaplan-Meier plotter revealed that OV patients with high ALKBH4 level showed longer overall survival (OS). However, patients with high levels of ALKBH5/6 and FTO showed shorter OS and progression-free survival (PFS). Genetic alterations using cBioPortal revealed that the alteration rates of FTO were the highest. We also found that the functions of AlkB family were linked to several cancer-associated signaling pathways, including chemokine receptor signaling. TIMER database indicated that the AlkB family had a strong relationship with the infiltration of six types of immune cells (macrophages, neutrophils, CD8+ T-cells, B-cells, CD4+ T-cells and dendritic cells). Next, DiseaseMeth databases revealed that the global methylation levels of ALKBH1/2/3/4/5/6/7/8 and FTO were all lower in OV patients. Thus, our findings will enhance the understanding of AlkB family in OV pathology, and provide novel insights into AlkB-targeted therapy for OV patients.In the present study, we studied the role of microRNA-30c-1 (miR-30c-1) on transforming growth factor beta1 (TGF-β1)-induced senescence of hCECs. hCECs were transfected by miR-30c-1 and treated with TGF-β1 to assess the inhibitory effect of miR-30c-1 on TGF-β1-induced senescence. Cell viability and proliferation rate in miR-30c-1-transfected cells was elevated compared with control. Cell cycle analysis revealed that cell abundance in S phase was elevated in miR-30c-1-treated cells compared with control. TGF-β1 increased the senescence of hCECs; however, this was ameliorated by miR-30c-1. TGF-β1 increased the size of hCECs, the ratio of senescence-associated beta-galactosidase-stained cells, secretion of senescence-associated secretory phenotype factors, the oxidative stress, and arrested the cell cycle, all of which were ameliorated by miR-30c-1 treatment. miR-30c-1 also suppressed a TGF-β1-induced depolarization of mitochondrial membrane potential and a TGF-β1 stimulated increase in levels of cleaved poly (ADP-ribose) polymerase (PARP), cleaved caspase 3, and microtubule-associated proteins 1A/1B light chain 3B II. In conclusion, miR-30c-1 promoted the proliferation of hCECs through ameliorating the TGF- β1-induced senescence of hCECs and reducing cell death of hCECs. Thus, miR-30c-1 may be a therapeutic target for hCECs regeneration.Colorectal cancer (CRC) is a prevalent malignancy worldwide. The development of genome sequencing technology has allowed the discovery that epigenetic regulation might play a critical role in CRC tumorigenesis. In the present study, we found that the long noncoding RNA (lncRNA) SNHG4 was dramatically increased in CRC tissue samples and cell lines based on both publicly available and experimental data. SNHG4 knockdown suppressed the viability and colony formation capacity of CRC cells. The expression of CDK1 was considerably increased in CRC tissue samples and cells and had a positive correlation with the expression of SNHG4 in CRC. SNHG4 silencing not only caused S phase cell cycle arrest but also significantly downregulated the CDK1, cyclin B1, and cyclin A2 protein levels in CRC cells. miR-590-3p simultaneously bound to SNHG4 and CDK1. Selleck AZD7762 miR-590-3p functioned to inhibit CDK1 expression. miR-590-3p overexpression exerted the same effects on the CRC cell phenotype as SNHG4 knockdown. The effects of si-SNHG4 on CRC cells were significantly reversed by anti-miR-590-3p, indicating that SNHG4 relieved the miR-590-3p-induced inhibition of CDK1 by acting as a competing endogenous RNA (ceRNA).