There are disparities for the association between uncoupling proteins (UCP) and type 2 diabetes (T2DM). The study was to examine the associations of genetic variants of UCP2 and UCP3 with prediabetes and T2DM in a rural Chinese population. A population-based case-control study of 397 adults with T2DM, 394 with prediabetes and 409 with normal glucose tolerance (NGT) was carried out in 2014 in a rural community in eastern China. Three groups were identified through a community survey and the prediabetes and NGT groups were frequently matched by age and gender with the T2DM group and they were not relatives of T2DM subjects. With r2 ≥ 0.8 and minor allele frequency (MAF) ≥0.05 for tag single nucleotide polymorphisms (SNPs) with potential function, three (rs660339, rs45560234 and rs643064) and six (rs7930460, rs15763, rs647126, rs1800849, rs3781907 and rs1685356) SNPs were selected respectively for UCP2 and UCP3 and genotyped in real time using the MassARRAY system (Sequenom; USA). The haplotypes, gene-environmental interaction and association between genetic variants of UCP2 and UCP3 and prediabetes or T2DM were explored. There were no significant differences in age and sex among three study groups. After the adjustment for possible covariates, the A allele of rs1800849 in UCP3 was significantly associated with prediabetes (aORAA vs GG = 1.68, 95% CI: 1.02–2.78), and the association was also significant under the recessive model (aOR AA vs GA + GG = 1.64, 95% CI: 1.02–2.66). Also, rs15763 was found to be marginally significantly associated with T2DM under dominant model (ORGA + AA vs GG = 0.73, 95% CI: 0.52–1.03, P = 0.072). No haplotype was significantly associated with prediabetes or T2DM. Multiplicative interactions for rs660339-overweight on T2DM were observed. In addition, the AA genotype of rs660339 was associated with an increased risk of T2DM in overweight subjects (OR = 1.48, 95%CI: 0.87–2.52) but with a decreased risk in those with normal weight (OR = 0.54, 95%CI: 0.28–1.05). Rs1800849 in UCP3 was significantly associated with prediabetes. Overweight might modify the effects of rs660339 of UCP2 on T2DM.

Inhibitors of DNA methylation such as 5-aza-deoxycytidine are widely used in experimental and clinical settings. However, their mechanism of action is such that DNA damage inevitably co-occurs with loss of DNA methylation, making it challenging to discern their respective effects. Here we deconvolute the effects of decreased DNA methylation and DNA damage on cancer cells, by using degron alleles of key DNA methylation regulators. We report that cancer cells with decreased DNA methylation—but no DNA damage—enter cellular senescence, with G1 arrest, SASP expression, and SA-β-gal positivity. This senescence is independent of p53 and Rb, but involves p21, which is cytoplasmic and inhibits apoptosis, and cGAS, playing a STING-independent role in the nucleus. Xenograft experiments show that tumor cells can be made senescent in vivo by decreasing DNA methylation. These findings reveal the intrinsic effects of loss of DNA methylation in cancer cells and have practical implications for future therapeutic approaches.

Epigenetic abnormalities are extremely widespread in cancer. Some of them are mere consequences of transformation, but some actively contribute to cancer initiation and progression; they provide powerful new biological markers, as well as new targets for therapies. In this review, we examine the recent literature and focus on one particular aspect of epigenome deregulation: large-scale chromatin changes, causing global changes of DNA methylation or histone modifications. After a brief overview of the one-dimension (1D) and three-dimension (3D) epigenome in healthy cells and of its homeostasis mechanisms, we use selected examples to describe how many different events (mutations, changes in metabolism, and infections) can cause profound changes to the epigenome and fuel cancer. We then present the consequences for therapies and briefly discuss the role of single-cell approaches for the future progress of the field.

Mycoplasma hominis (MH) is an opportunistic pathogen, which often causes funisitis, spontaneous abortion, and low birth weight. However, current laboratory methods are time-consuming, labor-intensive, or require specialized laboratory instruments. Recombinase polymerase amplification (RPA) technology is a rapidly developing field because of the significance for clinical application and commercial value. Few studies have reported the use of RPA to detect MH. In this study, we developed the rapid MH detection assay, which may be potentially used as a sensitive point-of-care testing (POCT) in clinic. Primers based on the MH 16SrRNA gene and gap gene were explored and screened out. The probe of RPA-LFD was designed based on the optimal primer and confirmed. The reaction conditions of temperature and time for RPA were optimized. The sensitivity and specificity of the analysis were explored. A total of 60 clinical specimens were used to verify the efficiency of the two methods. The optimal reaction conditions were determined as 15 minutes and 39°C. The sensitivity of RPA was 10-6 ng for MH, which is 100,000 times more sensitive than traditional PCR. Moreover, we observed another six non-target reproductive tract common pathogens without amplification products. Furthermore, we found that there was no significant difference between RPA and the cultivation method (p > 0.05). These two methods were in good agreement (κ = 0.938) when detecting clinical specimens. A new method for sensitive and rapid detection of MH based on RPA was successfully developed, which can be applied in large-scale screening and as a supplementary method to classical methods.