Effect of the combined intervention of low-FODMAPs diet and probiotics on IBS symptoms in Western China: A randomized controlled trial.

The effect of low-FODMAPs diet on irritable bowel syndrome (IBS) in Western China has not been reported. We aimed to investigate the effect of low-FODMAPs diet on IBS patients in the area and whether low-FODMAPs diet-induced alterations of microbiota could be improved through probiotics. IBS patients were randomized to the control group, low-FODMAPs diet group, probiotics group, or combined group. IBS Symptom Severity Score questionnaire (IBS-SSS) and IBS Quality of Life Score questionnaire (IBS-QOL) were completed at baseline, 2 and 4 weeks to evaluate the severity of symptoms. Fresh feces were collected for analyses of gut microbiota and short-chain fatty acids at baseline and 4 weeks after intervention. Seventy-three patients were included in the per protocol analysis. After intervention, there was significant improvement in IBS-SSS in the low-FODMAPs group (37.5%, 44.2%), probiotics group (51.4%, 62.0%), and combined group (34.1%, 40.4%) at both 2 weeks and 4 weeks, compared with the baseline (p < .05). In the low-FODMAPs group, the abundance of several microbiota (Lachnoclostridium, Enterococcus, etc.) was significantly decreased. Furthermore, after the supplementation of probiotics in the combined group, the abundance of Genus_Ruminococcus, Coprococcus, Acidaminococcus, Ruminiclostridium, Akkermansia, Eggerthella, and Oxalobacter was significantly increased, which was associated with the improvements of symptoms score in the Pearson correlation analysis. Our study confirmed the effectiveness and safety of short-term low-FODMAPs diet in IBS symptoms based on the Chinese diet in Western China. The combination of low-FODMAPs and probiotics plays a beneficial role in gut microbiota in IBS.

LPCAT1-mediated membrane phospholipid remodelling promotes ferroptosis evasion and tumour growth.

The mechanisms underlying the dynamic remodelling of cellular membrane phospholipids to prevent phospholipid peroxidation-induced membrane damage and evade ferroptosis, a non-apoptotic form of cell death driven by iron-dependent lipid peroxidation, remain poorly understood. Here we show that lysophosphatidylcholine acyltransferase 1 (LPCAT1) plays a critical role in ferroptosis resistance by increasing membrane phospholipid saturation via the Lands cycle, thereby reducing membrane levels of polyunsaturated fatty acids, protecting cells from phospholipid peroxidation-induced membrane damage and inhibiting ferroptosis. Furthermore, the enhanced in vivo tumour-forming capability of tumour cells is closely associated with the upregulation of LPCAT1 and emergence of a ferroptosis-resistant state. Combining LPCAT1 inhibition with a ferroptosis inducer synergistically triggers ferroptosis and suppresses tumour growth. Therefore, our results unveil a plausible role for LPCAT1 in evading ferroptosis and suggest it as a promising target for clinical intervention in human cancer.

Effects of oral oligopeptide preparation and exercise intervention in older people with sarcopenia: a randomized controlled trial.

BACKGROUND: Nutrition and exercise are important interventions for sarcopenia. There were few studies on oral oligopeptide nutrition preparations combined with exercise to intervene in the older people with sarcopenia. The aim of this study was to verify the effectiveness of oligopeptide nutrition preparation combined with exercise intervention on the older people with sarcopenia in community. METHODS: A total of 219 subjects aged 65 years or older with sarcopenia were randomly divided into 4 groups. The nutrition group (n = 58) was given individualized nutrition education and oral oligopeptide nutrition preparation. The exercise group (n = 50) received exercise intervention. The combined group (n = 52) received both oral nutrition preparation and exercise interventions. The control group (n = 59) only received individualized nutrition education. The nutrition preparation can provide energy 185kcal and protein 24.2g per day. The exercise intervention including warm-up exercise, resistance exercise and aerobic exercise, the training time was 60min for 5 times every week. The intervention lasted for 16 weeks. Hand grip strength, gait speed, body composition and hematology parameters were measured before and after intervention. RESULTS: A total of 159 subjects completed the study. Compared with baseline, the left grip strength and 6-m walking speed of the subjects in nutrition group increased significantly after the intervention, and the grip strength of both hands in exercise group and combined group increased significantly. The body weight of the subjects in nutrition group, exercise group and combined group increased significantly after intervention, but no increase in soft lean mass (SLM) and skeletal muscle mass (SMM) was observed in any of the four groups. The fat-free mass (FFM) of the legs of the control group, exercise group and nutrition group decreased after intervention, and only the FFM of the legs of the combined group maintained the level before the intervention. CONCLUSION: Both oral peptide nutrition and exercise interventions can improve the muscle strength or function of the older people with sarcopenia. However, there were no increases in muscle mass observed. TRIAL REGISTRATION: ChiCTR, ChiCTR2100052135. Registered 20 October 2021, https://www.chictr.org.cn/showproj.html?proj=135743.

Infiltrative Vessel Co-optive Growth Pattern Induced by IQGAP3 Overexpression Promotes Microvascular Invasion in Hepatocellular Carcinoma.

PURPOSE: Microvascular invasion (MVI) is a major unfavorable prognostic factor for intrahepatic metastasis and postoperative recurrence of hepatocellular carcinoma (HCC). However, the intervention and preoperative prediction for MVI remain clinical challenges due to the absent precise mechanism and molecular marker(s). Herein, we aimed to investigate the mechanisms underlying vascular invasion that can be applied to clinical intervention for MVI in HCC. EXPERIMENTAL DESIGN: The histopathologic characteristics of clinical MVI+/HCC specimens were analyzed using multiplex immunofluorescence staining. The liver orthotopic xenograft mouse model and mechanistic experiments on human patient-derived HCC cell lines, including coculture modeling, RNA-sequencing, and proteomic analysis, were used to investigate MVI-related genes and mechanisms. RESULTS: IQGAP3 overexpression was correlated significantly with MVI status and reduced survival in HCC. Upregulation of IQGAP3 promoted MVI+-HCC cells to adopt an infiltrative vessel co-optive growth pattern and accessed blood capillaries by inducing detachment of activated hepatic stellate cells (HSC) from the endothelium. Mechanically, IQGAP3 overexpression contributed to HCC vascular invasion via a dual mechanism, in which IQGAP3 induced HSC activation and disruption of the HSC-endothelial interaction via upregulation of multiple cytokines and enhanced the trans-endothelial migration of MVI+-HCC cells by remodeling the cytoskeleton by sustaining GTPase Rac1 activity. Importantly, systemic delivery of IQGAP3-targeting small-interfering RNA nanoparticles disrupted the infiltrative vessel co-optive growth pattern and reduced the MVI of HCC. CONCLUSIONS: Our results revealed a plausible mechanism underlying IQGAP3-mediated microvascular invasion in HCC, and provided a potential target to develop therapeutic strategies to treat HCC with MVI.

Nuclear translocation of cleaved PCDH9 impairs gastric cancer metastasis by downregulating CDH2 expression.

Loss of Protocadherin 9 (PCDH9) is associated with the metastasis and the prognosis of gastric cancer patients, while the molecular mechanism of PCDH9-impaired gastric cancer metastasis remains unclear. Here we show that PCDH9 is cleaved in gastric cancer cells. Intracellular domain of PCDH9 translocates into nucleus, where it interacts with DNA methyltransferase 1 (DNMT1) and increases DNMT1 activity. Activated DNMT1 downregulates cadherin 2 (CDH2) expression by increasing DNA methylation at its promoter, thereby dampening the migration and in vivo metastasis of gastric cancer cells. In addition, the levels of nuclear PCDH9 correlate with CDH2 expression, lymph node metastasis, and the prognosis of gastric cancer patients. Our finding demonstrates a unique mechanism of nuclear PCDH9-impaired gastric cancer metastasis by promoting DNA methylation of CDH2 promoter.