The bidirectional association of C-peptide with cardiovascular risk in nondiabetic adults and patients with newly diagnosed type 2 diabetes mellitus: a retrospective cohort study.

BACKGROUND: Recent literature reported the biological role of C-peptide, but this role is still controversial and unclear. The primary aim of this study was to investigate associations between C-peptide and cardiovascular biomarkers as well as events. METHODS: A total of 55636 participants who had a health examination from 2017 to 2021 were included. Of them, 6727 participants visited the hospital at least twice. Cardiovascular biomarkers like high-sensitivity C-reactive protein (hs-CRP) and high-sensitivity cardiac troponin T (hs-cTnT) were measured and their relationships with fasting C-peptide were evaluated for all participants. Cardiovascular events were obtained during the last visit and their associations with C-peptide were evaluated for those participants who visited the hospital at least twice. RESULTS: Among the included participants, 11.1% had a previous type 2 diabetes mellitus (T2DM). In the participants without previous T2DM, the relationships between fasting C-peptide and hs-CRP and hs-cTnT were negative if the value of fasting C-peptide was < 1.4 ng/mL and positive if the value was ≥ 1.4 ng/mL. These relationships remained significant after adjusting for hemoglobin A1c, insulin resistance index, and its interaction with C-peptide, even if the participants were stratified by glucose metabolism status or levels of insulin resistance index. Hazard ratios of cardiovascular events were first decreased and then increased with the increasing of baseline C-peptide levels, though these associations became unsignificant using the multivariate Cox regression model. Unlike the participants without previous T2DM, the associations of C-peptide with cardiovascular biomarkers and events were not significant in the patients with previous T2DM. CONCLUSIONS: The associations of C-peptide with cardiovascular biomarkers and events were different between the participants without previous T2DM and those with previous T2DM. The effect of C-peptide on cardiovascular risk may be bidirectional, play a benefit role at a low level, and play a harmful role at a high level in the nondiabetic adults and the patients with newly diagnosed T2DM.

Deficiency of NARFL increases transcription of NADPH oxidases and ROS production impairing the function of endothelial cells.

AIMS: Nuclear prelamin A recognition factor-like (NARFL) is involved in cytosolic iron­sulfur (FeS) protein biogenesis and cellular defense against oxidative stress. Previous study reported that increased oxidative stress and subintestinal vessel (SIV) malformation in narfl knockout zebrafish. However, the underlying mechanism of oxidative stress caused by NARFL deficiency remains unclear. The present study was sought to investigate the function of NARFL in endothelial cells. METHODS: NARFL knockdown assay was performed in two cell lines and NADPH oxidase (Nox) were measured using Western blotting. Nox inhibitors were selected for assessing the potential sources of reactive oxygen species (ROS) generation. Cell migration was detected using wound healing assay and transwell assay. Cell cycle was analyzed using flow cytometry. Promoter activity assay and Chromatin immunoprecipitation (ChIP) assay were chosen for investigating the molecular mechanism of Nox transcription. RESULTS: NARFL deficiency resulted in upregulated expressions of Nox2, Nox4, and p47phox and increased ROS levels in endothelial cells. Nox2 knockdown reversed the effects and improved endothelial dysfunctions caused by NARFL deficiency. ChIP experiments revealed that NARFL knockdown increased the recruitment of RNA polymerase II and modification of histones at the promoter sites of Nox2 and Nox4. CONCLUSION: NARFL knockdown induced the transcriptional activation of Nox2 and Nox4, which resulted in increased ROS levels and impaired endothelial functions.

Introducing electrolysis to enhance anaerobic digestion resistance to acidification.

The phenomenon that the anaerobic system is inhibited by acid has always been a bottleneck hindering the application of anaerobic digestion (AD) technology. We tried to introduce electrolysis into AD to improve the acidification resistance, and eventually the productivity of the energy. In a batch fermentation device, the ability of electrochemical anaerobic digestion (EAD) to resist acidification was evaluated in current intensity, electrode potential, AC impedance, microbial community, pH value, and volatile fatty acids (VFAs). The results showed that the average concentration of VFAs in EAD was 32.9% lower than that in AD, the energy efficiency of EAD is 53.25% higher than AD, indicating that EAD has stronger anti-acidification ability and energy conversion efficiency than AD. When the EAD reaches a steady state, the current intensity fluctuates in the range of 7-12 mA, the electrode potential difference is maintained at 600 ± 5 mV, and the internal resistance decreases from 3333.3 ± 16Ω at startup to 68.9 ± 1.4Ω at the steady state, indicating that the EAD has stronger resistance to acidification may be due to the degradation of some VFAs on the electrode surface. Furthermore, the 16S rRNA sequencing analysis showed that the dominant electricity-producing bacteria on EAD anode surface were Clostridium, Hydrogenophaga and Trichloromonas, with a relative abundance of 40.32%, while the relative abundance of electrogenic bacteria in AD bulk solution and EAD bulk solution were about 1/2 and 1/4 that of EAD anode film, suggesting that the electricity-producing bacteria on the electrode surface play an important role in the degradation of VFAs.

A novel mutation in nuclear prelamin a recognition factor-like causes diffuse pulmonary arteriovenous malformations.

Two daughters in a Chinese consanguineous family were diagnosed as diffuse pulmonary arteriovenous malformations (PAVMs) and screened using whole exome sequencing (WES) and copy number variations (CNVs) chips. Though no mutation was found in the established causative genes of capillary malformation-AVMs (CM-AVMs) or PAVMs, Ser161Ile (hg19 NM_022493 c.482G>T) mutation in nuclear prelamin A recognition factor-like (NARFL) was identified. Ser161Ile mutation in NARFL conservation region was predicted to be deleterious and absent in 500 population controls and Exome Aggregation Consortium (ExAC) Database. And there was a dosage effect of the mutation on mRNA levels among family members and population controls, consistent with the instability of mutant mRNA in vitro. Accordingly, in lung tissue of the proband, NARFL protein expression was reduced but Fe3+ was overloaded with vascular endothelial growth factor (VEGF) overexpression. Furthermore, NARFL-knockdown cell lines demonstrated decreased activity of cytosolic aconitase, while NARFL-knockout zebrafish presented ectopic subintestinal vessels sprouts and upregulated VEGF. So we concluded that the Ser161Ile mutant induced NARFL deficiency and eventually diffuse PAVMs probably through VEGF pathway. In a word, we detected a functional mutation in NARFL, which might be the pathogenic gene in this pedigree.

MicroRNA­187 is an independent prognostic factor in lung cancer and promotes lung cancer cell invasion via targeting of PTRF.

MicroRNAs (miRNAs) are involved in the progression of different types of cancers giving new hope for cancer treatment. The role and regulatory mechanism of microRNA­187 (miR­187) are largely unknown. In the present study, 74 patients with non­small cell lung cancer (NSCLC) were selected. Tumor tissues and matched normal tissues were collected for determining the expression level of miR­187. Cell research was performed to detect the function of miR­187. The expression level was measured and miR­187 was found to be overexpressed in the NSCLC cell lines and tissues. Overexpression of miR­187 promoted cell proliferation in the A549 and H1650 cell lines. Moreover, overexpression of miR­187 also promoted cell migration and invasion. Polymerase I and transcript release factor (PTRF) was identified as a target of miR­187. Overexpression of miR­187 suppressed the expression of PTRF. Knockdown of PTRF promoted lung cancer cell invasion, and overexpression of PTRF had a negative effect on lung cancer cell invasion. The PTRF messenger RNA (mRNA) levels in cancer tissues were significantly lower than those in their adjacent normal lung tissues as determined by real­time PCR (RT­PCR). The expression of the PTRF protein was significantly weaker than that in the adjacent normal lung tissues using immunohistochemical staining. The findings revealed that miR­187 promotes cell growth and invasion by targeting PTRF and miR­187 may be a new prognostic factor for NSCLC.

Glutathione S-transferase M1 null genotype and hepatocellular carcinoma susceptibility in China and India: evidence from an updated meta-analysis.

BACKGROUND: Glutathione S-transferase M1 (GSTM1) have been reported to be associated with hepatocellular carcinoma. However, the effect of the GSTM1 null genotype was divergent in the literature and we therefore performed the present meta-analysis to explore the relationship in detail. MATERIALS AND METHODS: Reported studies were searched from 1990 to March 1, 2014 in PubMed and Wanfang Med Online. The total odds oatio (OR) and 95% CI were calculated and analyzed by Review Manager 5.1 and STATE 12. RESULTS: Total OR was calculated from 26 articles with 3,769 cases and 5,517 controls and the association proved significant (OR [95%CI]=1.50 [1.25, 1.80], P<0.05) in the Chinese population. However, there was no significant association between hepatocellular carcinoma risk among subjects carrying the GSTM1 null genotype (OR [95%CI]=1.20 [0.88-1.64], P=0.24) in subgroups of publication in English and in Indian populations (OR [95%CI]=1.80 [0.80- 4.20], P=0.15). CONCLUSIONS: The GSTM1 deletion polymorphism might not have a significant effect on the susceptibility of hepatocellular carcinoma overall.

Null Glutathione S-transferase T1 and M1 genotypes and oral cancer susceptibility in China and India--a meta-analysis.

OBJECTIVE: Genetic variation is considered to strongly impact on detoxification of carcinogens and therefore is related to cancer risk. However, findings for the null genotypes of GSTT1 and GSTM1 have not always been consistent. Therefore the present meta-analysis was conducted. METHODS: We accessed the reported study at different research areas and used various databases, including PubMed and Wanfang Med Onlion from 1990 to May 1st 2013. We calculated the odds ratio (OR), 95% confidence interval (CI) and P value for oral cancer by using Review Manager 5.1 and STATE 12. RESULTS: We found that there was no increased oral cancer risk among subjects carrying GSTM1 and GSTT1 null genotype (OR=1.35, 95%CI=0.68-2.68, P=0.39) and (OR=1.41, 95%CI=0.72-2.77, P=0.31) in the Chinese population. In contrast, in studies in India a significant correlation between GSTM1 null genotype and oral cancer was observed (OR=1.59, 95%CI=1.20-2.11, P=0.001), but not in GSTT1 (OR=1.21, 95% CI = 0.84-1.74, P=0.31). CONCLUSION: We discovered that GSTM1 deletion polymorphism had a significant effect on the susceptibility of oral cancer in the Indian population.

Lack of assocation of glutathione S-transferase T1 gene null and susceptibility to lung cancer in china: a meta-analysis.

BACKGROUND: Variation in metabolic genes is regarded as an important factor in processes leading to cancer. However, the effect of GSTT1 null genotype is divergent in the form of lung cancer. METHODS: Studies were conducted at different research databases from 1990 to 2013 and the total odds ratio (OR) and 95% confidence interval (CI) were calculated for lung cancer. Review Manager 5.2 and STATE 12 are employed. RESULTS: Total OR value is calculated from 17 articles with 2,118 cases and 2,915 controls. We discovered no significant increase in lung cancer risk among subjects carrying GSTT1 null genotype [OR = 1.15; 95% CI 0.97-1.36] in this meta- analysis. CONCLUSION: The GSTT1 deletion polymorphism does not have a significant effect on the susceptibility to lung cancer overall in China.