Ingestion of Lactobacillus helveticus WHH1889 improves depressive and anxiety symptoms induced by chronic unpredictable mild stress in mice.

Emerging evidence indicates that the alterations in the gut microbiota-brain axis (GBA), which is the bilateral connection between the gut microbial communities and brain function, are involved in several mental illnesses, including depression. Certain probiotic strains have been revealed to improve depressive behaviours and the dysregulation of 5-hydroxytryptamine (5-HT) metabolism in depression. Here we evaluated the potential antidepressant effects of Lactobacillus helveticus strains using an in vitro enterochromaffin cell model (RIN14B). The L. helveticus strain WHH1889 was shown to significantly promote the level of 5-hydroxytryptamine (5-HTP, 5-HT precursor) and the gene expression of tryptophan hydroxylase 1 (Tph1), which is the key synthetase in the 5-HT biosynthesis in RIN14B cells. Ingestion of 0.2 ml WHH1889 (1´109 cfu/ml) in a chronic unpredictable mild stress (CUMS) mouse model of depression for five weeks normalised depressive and anxiety-like behaviours in the forced swim test, tail suspension test, sucrose preference test, and open field test. Meanwhile, the CUMS-induced elevated level of serum corticosterone and declined levels of hippocampal 5-HT and 5-HTP were reversed by WHH1889. Furthermore, the disturbances of the gut microbiome composition with reduced microbial diversity were also improved by WHH1889, accompanied by the increased colonic 5-HTP level and Tph1 gene expression. In summary, these findings indicate that WHH1889 exerts antidepressant-like effects on CUMS mice, which is associated with the modulations of the 5-HT/5-HTP metabolism and gut microbiome composition. Therefore, ingestion of the L. helveticus strain WHH1889 with antidepressant potentials may become an encouraging therapeutic option in the treatment of depression.

Hsa-miR-34a-5p reverses multidrug resistance in gastric cancer cells by targeting the 3'-UTR of SIRT1 and inhibiting its expression.

Multidrug resistance (MDR) is a major obstacle to chemotherapy, which leads to ineffective chemotherapy, an important treatment strategy for gastric cancer (GC). The abnormality of microRNAs (miRNAs) is critical to the occurrence and progression of MDR in various tumors. In this study, hsa-miR-34a-5p was found to be decreased in multidrug resistant GC cells SGC-7901/5-Fluorouracil (SGC-7901/5-Fu) compared to the parental SGC-7901 cells. Overexpression of hsa-miR-34a-5p in SGC-7901/5-Fu cells promoted apoptosis and decreased migration and invasiveness after chemotherapy. In addition, overexpression of hsa-miR-34a-5p suppressed the growth of drug-resistant tumor in vivo. The mechanism of the effects of hsa-miR-34a-5p could include the regulation of the expression of Sirtuin 1 (SIRT1), P-glycoprotein (P-gp) or Multidrug resistance-related protein 1 (MRP1) through direct binding to the 3'-untranslated region (UTR) of SIRT1. Functional gain-and-loss experiments indicated that hsa-miR-34a-5p enhances the chemotherapy sensitivity of MDR GC cells by inhibiting SIRT1, P-gp and MRP1. In conclusion, hsa-miR-34a-5p can reverse the MDR of GC cells by inhibiting the expression of SIRT1, P-gp or MRP1.

50-Hz magnetic field induces EGF-receptor clustering and activates RAS.

PURPOSE: In a previous study, we found that exposure to a 50 Hz magnetic field (MF) could activate stress-activated protein kinase (SAPK) and P38 mitogen-activated protein (MAP) kinase (P38 MAPK) in Chinese hamster lung (CHL) fibroblast cells, and simultaneous exposure to a 'noise' MF of the same intensity inhibited these effects. In order to explore the possible target sites and upstream signal transduction molecules of SAPK and P38 MAPK, and further validate the interference effects of 'noise' MF on 50 Hz MF, the effects of MF exposure on clustering of epidermal growth factor (EGF) receptors and Ras protein activation were investigated. MATERIALS AND METHODS: CHL cells were exposed to a 50 Hz sinusoidal MF at 0.4 mT for different durations, and clustering of EGF receptors on cellular membrane and Ras protein activation were analyzed using immunofluorescence confocal microscopy and co-precipitation technology. EGF treatment served as the positive control. RESULTS: The results showed that, compared with sham-exposed cells, exposure to a 50 Hz MF at 0.4 mT for 5 min slightly induced EGF receptor clustering, whereas exposure for 15 min enhanced receptor clustering significantly. Corresponding to receptor clustering, Ras protein was also activated after exposure to the 50 Hz MF. Exposure to a 'noise' MF (with frequency ranges from 30 - 90 Hz) at the same intensity and durations, did not significantly affect EGF receptor clustering and Ras protein. However, by superimposing the 'noise' MF, receptor clustering and Ras activation induced by 50 Hz MF were inhibited. CONCLUSION: The results suggested that membrane receptors could be one of the most important targets where extremely low frequency (ELF) MF interacts with cells, and Ras may participate in the signal transduction process of 50 Hz MF. Furthermore, a 'noise' MF could inhibit these effects caused by ELF-MF.