Impaired intestinal stem cell activity in ETEC infection: enterotoxins, cyclic nucleotides, and Wnt signaling.

Enterotoxigenic Escherichia coli (ETEC) in humans and animals colonizes the intestine and thereafter secrets heat-stable enterotoxin (ST) with or without heat-labile enterotoxin (LT), which triggers massive fluid and electrolyte secretion into the gut lumen. The crosstalk between the cyclic nucleotide-dependent protein kinase/cystic fibrosis transmembrane conductance regulator (cAMP or cGMP/CFTR) pathway involved in ETEC-induced diarrhea channels, and the canonical Wnt/ß-catenin signaling pathway leads to changes in intestinal stem cell (ISC) fates, which are strongly associated with developmental disorders caused by diarrhea. We review how alterations in enterotoxin-activated ion channel pathways and the canonical Wnt/ß-catenin signaling pathway can explain inhibited intestinal epithelial activity, characterize alterations in the crosstalk of cyclic nucleotides, and predict harmful effects on ISCs in targeted therapy. Besides, we discuss current deficits in the understanding of enterotoxin-intestinal epithelial cell activity relationships that should be considered when interpreting sequelae of diarrhea.

HSD3B1 variant and androgen-deprivation therapy outcome in prostate cancer.

OBJECTIVE: Rate-limiting enzyme 3b-hydroxysteroid dehydrogenase type 1 (3ßHSD1) encoded by HSD3B1 catalyzes the transition of dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT). The HSD3B1 (1245C) variant renders 3bHSD1 of resistant to ubiquitination and degradation, leading to a large amount of protein accumulation in the cell. Multiple clinical studies have shown that this mutation was correlated with resistance to androgen-deprivation therapy in prostate cancer. However, the results were not consistent depending on different treatment strategy and in some researches, the number of observed cases was relatively small. METHODS: To determine the effects of HSD3B1 (1245C) variant on resistance to androgen-deprivation therapy in prostate cancer, we performed a meta-analysis of the available literature. Electronic database searches identified appropriately designed studies that detected HSD3B1 in prostate cancer. We conducted a systematic search of studies in the following databases: PubMed, and EMBASE published until August 10, 2020 using the following search terms: (HSD3B1 AND ((((prostate cancer) OR prostatic neoplasm) OR prostatic carcinoma) OR prostatic cancer). RESULTS: Eight researches were included in this research. The result validated that the HSD3B1 (1245C) variant allele was associated with a shorter PFS (HR, 1.97; 95% CI, 1.39-2.79; P = 0.0001) (homozygous wild-type group) in men with prostate cancer when treated with ADT, however, a higher PFS (HR, 0.68; 95% CI, 0.48-0.96; P = 0.03) when treated with ADT and CYP17A1 inhibitor. CONCLUSION: The HSD3B1 (1245C) variant is a predictor of ADT plus CYP17A1 inhibitor response in prostate cancer.

Cytomegalovirus Infection Is a Risk Factor in Gastrointestinal Cancer: A Cross-Sectional and Meta-Analysis Study.

BACKGROUND: This study was planned to investigate the association betweenhuman cytomegalovirus (HCMV) infection and gastrointestinal cancer (GIC) risk, by undertaking a meta-analysis and case-control cross-sectional study. SUMMARY: A cross-sectional study analysis of 160 GIC patients and 100 control subjects indicated significantly higher HCMV prevalence in GIC patients based on the HCMV IgM test. However, a similar analysis based on an IgG test revealed no significant relationship. Further meta-analysis of 11 studies, including 1,044 patients and 991 healthy subjects, displayed HCMV infection as an important risk factor for not only colorectal cancer occurrence and development based on a HCMV DNA test, but also for GIC based on a HCMV IgM test. However, the IgG test again displayed no significant relationship between HCMV infection and GIC occurrence. Key Message: Overall, our study revealed that HCMV infection is associated with an increased GIC risk. However, additional studies are warranted to elucidate the molecular mechanism underlying this association.

Curcumin inhibits the formation of atherosclerosis in ApoE-/- mice by suppressing cytomegalovirus activity in endothelial cells.

BACKGROUND: Curcumin (Cur) is a hydrophobic polyphenol compound derived from the rhizome of the herb Curcuma longa. Cur has a wide spectrum of biological and pharmacological activities. It has been shown that human cytomegalovirus (HCMV) infection was an important risk factor for atherosclerosis (AS) and Cur exhibited an outstanding anti-HCMV effect. However, anti-AS effects of Cur remain unclear when HCMV infected endothelial cells. AIMS: This study will investigate the anti-AS activities and mechanism of Cur,when HCMV infected in vivo and in vitro. MATERIALS AND METHODS: Cur (0.5, 1, and 2 µM) was used to explore the anti-AS activities and mechanism after HCMV infected endothelial cells in vitro. ApoE-/- mice were fed a high fat and cholesterol diet (HD) and given 4000,000 copies/mouse MCMV infection by intraperitoneal and treated with ganciclovir (5 mg/kg/d), Cur (25, 15 mg/kg/d) for 10 weeks in vivo. KEY FINDINGS: As our results showed that Cur inhibited CMV replication and proliferation, reduced the intracellular ROS overproduction, decreased the release of inflammatory cytokines, down-regulated the level of HMGB1-TLRS-NF-κB signaling pathway-related proteins in vitro experiments. Cur reduced the serum levels of LDL-C, TC and TG, significantly decreased the formation of atherosclerotic plaque in the aorta, reduced the lipid deposition in liver and inflammatory damage in heart, lung and kidney in vivo experiments. SIGNIFICANCE: This study showed that Cur prevent AS progression by inhibiting CMV activity and CMV-induced HMGB1-TLRS-NF-κB signaling pathway.

Enhanced anodic electrochemiluminescence of CdTe quantum dots based on electrocatalytic oxidation of a co-reactant by dendrimer-encapsulated Pt nanoparticles and its application for sandwiched immunoassays.

Herein, we synthesized Pt dendrimer-encapsulated nanoparticles (Pt DENs) using amine-terminated sixth-generation polyamidoamine dendrimers. The enhanced and stable anodic electrochemiluminescence (ECL) of 3-mercaptopropionic acid-capped CdTe quantum dots (QDs) in a tripropylamine solution was achieved owing to Pt DENs. The reason may be that Pt DENs exhibit high catalytic electrochemical oxidation in the presence of tripropylamine and excellent conductive property. Inspired by this, Pt DENs were conjugated with Fe3O4@SiO2 nanoparticles and served as nano-carriers. The capture antibodies were immobilized on the Fe3O4@SiO2-Pt DEN nanocomposites, which possess many attractive advantages such as the ease of bioconjugation, large specific surface area, and convenience of magnetic separation. Fluorescence microscopy images and UV-vis spectra were used to verify the immobilization of capture antibodies on the nanocomposites. The CdTe QDs were applied as signal labels for conjugation of nanocomposites with detection antibodies, which were characterized by agarose gel electrophoresis. Electrochemical impedance spectroscopy and cyclic voltammetry demonstrated the successful preparation of an ECL immunosensor. Under the optimal conditions, the proposed immunosensor provided a wide linear range from 0.005 ng mL-1 to 150 ng mL-1 with a detection limit of 0.2 pg mL-1 (S/N = 3) for the detection of carcinoembryonic antigen. Moreover, the immunosensor showed good performance for the detection of carcinoembryonic antigen in serum samples as well as great potential in clinical bioassay.

[Levels, Sources, and Health Risk Assessments of Heavy Metals in Indoor Dust in a College in the Pearl River Delta].

Thirty indoor dust samples were collected from staff and study areas in a college in Foshan, and the As, Hg, Cd, Cu, Zn, Ni, Pb, and Cr contents were measured. The Spearman correlation coefficient, principal component analysis, and US EPA health risk assessment model were used to determine the sources and degree of pollution and the health risks. The results showed that the levels of the eight heavy metals were higher than the background values in Guangdong Province and the reported values in other Chinese cities, excluding Hg. The levels of the eight heavy metals were higher in the staff area than in the study area, but the difference was not significant. The eight heavy metals were derived from similar sources; Hg was mainly derived from outdoor anthropogenic sources, while the others were mainly derived from indoor anthropogenic sources. The daily non-carcinogenic exposure dose was in the following order:ingestion > dermal exposure > inhalation. Ingestion was the major pathway of heavy metal exposure from indoor dust. Except for Cr, the non-carcinogenic hazard indexes of ingestion and dermal exposure were taken from partial sample points > 1. All of the health risks were lower than the average risk thresholds of the heavy metals, and would not cause health risks to humans. Printers, copiers, instruments, and equipment were important sources of indoor pollution and risk sources of heavy metals. Thus, protective measures should be taken to reduce the risk of exposure.