Subchronic exposure to PM2.5 induced renal function damage and intestinal microflora changes in rats.

BACKGROUND: Exposure to inhalable environmental particulate matter with a diameter of 2.5 µm or smaller (PM2.5) is associated with decreased or impaired kidney function, but the underlying biological mechanisms are not fully understood. Gut microbiota is an emerging key player in the homeostasis regulation of the gut-kidney axis. Few studies have investigated its role in PM2.5 exposure-induced gut-kidney axis homeostasis abnormalities. METHODS: In this study, a versatile aerosol concentration enrichment system for medium- to long-term whole-body exposure was used to expose Sprague-Dawley rats to filtered air (FA) or concentrated ambient PM2.5 for 12 weeks. A correlation analysis of renal impairment and the intestinal microbiome was performed. RESULTS: The urine flow rate calculation and renal function analysis showed that PM2.5 exposure significantly impaired renal function and increased the urine flow rate. The fecal microbiota analysis showed that renal impairment and increased urine flow rates were consistent with the reduced estimates of the fecal bacteria Chao1, observed-species, Shannon, and Simpson (richness and diversity indices). Pearson's correlation analysis showed that the estimated bacterial richness and diversity were correlated with the urine flow rate and renal function. The linear discriminant analysis effect size (LEfSe) analysis revealed differences between animals exposed to PM2.5 and FA in 25 bacterial groups. Further correlation of a single bacterial taxon with the urine flow rate and renal function showed that the relative abundances of 30, 29, 21, and 50 distinct bacterial groups were significantly correlated with the urine flow rate, estimated glomerular filtration rate (eGFR), serum cystatin C (CysC), and beta-2 microglobulin (ß2-MG), respectively. CONCLUSION: Subchronic exposure to PM2.5 can cause intestinal ecological disorders, which may, in turn, lead to decreased kidney function or the development of impaired kidney function.

Effect of folic acid supplementation in the association between short sleep duration and gestational diabetes mellitus.

PURPOSE: To examine whether or not folic acid (FA) supplementation may modify the relationships between duration or quality of sleep and gestational diabetes mellitus (GDM) risk. METHODS: In a case-control study of patients with GDM and controls, mothers were interviewed face-to-face at enrollment. The Pittsburgh Sleep Quality Scale was used to assess duration and quality of sleep during early pregnancy, and information on FA supplementation and covariates was obtained using a semiquantitative questionnaire. RESULTS: Among 396 patients with GDM and 904 controls, GDM risk increased by 328% and 148% among women with short (< 7 h) and long (≥ 9 h) sleep durations, respectively, compared to those averaging 7-8.9 h sleep. Mothers with poor sleep quality increased their GDM risk by an average of 75% (all p < 0.05). The effect of short sleep duration on GDM risk was much weaker among women with adequate FA supplementation (taking supplements containing ≥ 0.4 mg FA daily for each day of the first three months of pregnancy) than that among women with inadequate FA supplementation, with a p-value for interaction = 0.003. There were no significant effects of FA on links among long duration and poor quality of sleep with GDM risk. CONCLUSIONS: Sleep duration and quality in early gestation were related to increased GDM risks. FA supplementation may reduce GDM risk associated with short sleep duration.

U-shaped Association Between Folic Acid Supplementation and the Risk of Gestational Diabetes Mellitus in Chinese Women.

OBJECTIVE: Our aim in this study was to assess the association between folic acid (FA) supplementation before and during pregnancy and risk of gestational diabetes mellitus (GDM) in Chinese women. METHODS: This case-control study was conducted at 2 hospitals in central China. A total of 1,300 pregnant women, including 396 GDM patients and 904 controls, participated in the study. Information on the dose and duration of FA supplementation was collected using a self-report questionnaire at enrolment (24 to 28 weeks of gestation). RESULTS: We observed a U-shaped association between FA supplementation and GDM risk that demonstrated a 228% increased risk of GDM among women who never took FA supplements, a 28% increased risk among women who took supplements containing <400 µg/day FA or took FA supplements for <1 month and a 188% increased risk among women who took supplements containing ≥800 µg/day FA for an adequate duration (>1 month before pregnancy and >3 months during pregnancy) compared with women who took supplements containing 400 to 799 µg/day FA for an adequate duration (all p<0.05). For women who took supplements containing ≥800 µg/day FA for an adequate duration, the association between FA supplementation and GDM risk appeared to be stronger among those women with a prepregnancy body mass index (BMI) of ≥25 kg/m2 than among those with a prepregnancy BMI of <25 kg/m2 (p=0.006 for interaction). CONCLUSIONS: There was a U-shaped association of FA supplementation with GDM risk; that is, FA supplementation both below and above the recommended levels may increase the risk of GDM.

Portulaca oleracea polysaccharides reduce serum lipid levels in aging rats by modulating intestinal microbiota and metabolites.

Metabolic diseases characterized by dyslipidemia are common health problems for elderly populations. Dietary fiber intake is inversely associated with the risk of dyslipidemia. This study investigated the effects of Portulaca oleracea polysaccharide (POP) on the intestinal microbiota and its metabolites in aging rats using 16S rRNA sequencing and metabolomics techniques. Our results showed that POPs reduced the ratio of Firmicutes/Bacteroidetes (F/B), relative abundance of Fusobacteria, and levels of triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), and gamma-glutamyl transferase (γ-GT) in the serum of aging rats. POP supplementation also reduced 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol, and vaccenic acid concentrations in lipids and lipoid-like molecules, while soyasapogenol E and monoacylglycerol (MG) (24:0/0:0/0:0) levels increased. This study demonstrated that POP's beneficial effects on lipid levels in aging rats might be partially attributable to the modification of gut microbiota and related metabolites.

Portulaca oleracea Polysaccharides Modulate Intestinal Microflora in Aged Rats in vitro.

To explore the effect of Portulaca oleracea polysaccharides (POP) in regulating intestinal microflora in aged rats in vitro, its intestinal microbial composition was analyzed by 16 S rDNA high-throughput sequencing, and the level of short-chain fatty acids in fermentation broth was determined by LC-MS. POP significantly upregulated the relative abundance of Lactobacillus, Eggerthella, and Paraprevotella and significantly downregulated Escherichia_Shigella, Bacteroides, and Eubacterium nodatum groups. The pH value and ammonia nitrogen level decreased significantly in the POP-treated group, resulting in a more short-chain fatty acid consumption which changed the acid-base environment of the fermentation broth. In conclusion, POP is beneficial to aged rats because it can regulate intestinal flora, promote the growth of probiotics, and inhibit the reproduction of pathogenic bacteria.

The promising antitumour drug disulfiram inhibits viability and induces apoptosis in cardiomyocytes.

Disulfiram (DSF), widely used for treating alcohol abuse, is a promising antitumour drug that inhibits tumour cell viability, reverses cancer drug resistance and induces apoptosis. However, its potential side effects on cardiomyocytes remain unknown. This study demonstrated that DSF can not only inhibit cardiomyocyte viability and activity but also promote cell apoptosis. Furthermore, we revealed that cardiomyocytes were more sensitive to DSF than cancer cells. Moreover, the expression of STAT3, a key regulator of cardiomyocyte viability, was significantly down-regulated in cardiomyocytes treated with DSF. Finally, we also used experimental comparisons to indicate that PEG is a promising solvent for decreasing the adverse side effects of DSF, thereby expanding its potential range of clinical applications.

Tamoxifen Attenuates Lipopolysaccharide/Galactosamine-induced Acute Liver Failure by Antagonizing Hepatic Inflammation and Apoptosis.

Bacterial lipopolysaccharide (LPS)-induced acute liver failure (ALF) is a common severe clinical syndrome in intensive care unit. No other methods are available for its prevention apart from supportive treatment and liver transplantation. Tamoxifen (TAM) was reported to attenuate ALF induced by excessive acetaminophen, while its effect on LPS-induced ALF remained unknown. For this, in the present study, we comprehensively assessed whether TAM can attenuate ALF induced by LPS/galactosamine (GaIN). Mice were given TAM once a day for three times. Twelve hours after the last treatment, mice were given LPS/GaIN (intraperitoneally [i.p.]). Survival, plasma transaminases, and histopathology were examined. Serum TNF-α and IL-1ß were analyzed by ELISA. Hepatic apoptosis was analyzed by TUNEL and caspase-3 Western blotting, respectively. Compared to the model group, ALF induced by LPS/GaIN was alleviated remarkably following TAM administration, as evidenced by the improvement of survival (87.5% vs. 37.5%), hepatic swell, moderate transaminases, slightly increased serum TNF-α, IL-1ß (P < 0.05), and moderate histopathology. In respect of apoptosis, severe hepatocellular apoptosis was reduced notably by TAM treatment confirmed by less TUNEL-positive hepatocytes and decreased caspase-3 cleavage. The results demonstrated that TAM could attenuate LPS/GaIN-induced ALF effectively, probably due to hepatic inflammation and apoptosis antagonism. Furthermore, it was the first report about the effect of TAM on LPS/GaIN-induced ALF.

A diet with lactosucrose supplementation ameliorates trinitrobenzene sulfonic acid-induced colitis in rats.

Chronic intestinal inflammation contributes to an increased risk of colon cancer. Lactosucrose (LS), a kind of functional trisaccharide, can modulate immunity and promote microbe growth. The aim of this study was to investigate the effect of LS on 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced colitis in rats. Rats were randomly divided into four treatment groups: the normal group, TNBS group, LS group, and salicylazosulfapyridine (SASP) group for five weeks. LS supplementation ameliorated TNBS-induced colitis. LS supplementation increased IL-10 production and suppressed the secretion of IL-12 in the colon, as compared to the TNBS group. LS decreased the production of TLR-2 protein and nuclear NF-κB p65 protein, as well as mRNA levels, as compared with colitic rats. These results indicate that chronic feeding of LS inhibited TNBS-induced chronic inflammation. LS has potential nutraceutical intervention to combat colitis.

Lactosucrose attenuates intestinal inflammation by promoting Th2 cytokine production and enhancing CD86 expression in colitic rats.

Some oligosaccharides have immunoregulatory and anti-inflammatory functions in the intestine. This study investigated the immunoregulatory effect of lactosucrose (LS) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitic rats. Alkaline phosphatase activity was increased but myeloperoxidase activity was decreased in the LS-TNBS group, as compared with the TNBS group (colitis rats without receiving LS). LS supplementation stimulated IL-4 and IL-10 production, while up-regulating CD86 expression in dendritic cells. LS supplementation reduced the ratio of CD80/CD86 and the ratio of IFN-γ/IL-4 compared to the TNBS group. Moreover, IFN-γ was significantly correlated with CD80 (r = 0.764, p < 0.01), whereas IL-4 was significantly correlated with CD86 (r = 0.489, p < 0.05). These results indicated that LS attenuated colitis by promoting the production of Th2-type cytokines and rebalancing the ratio of Th1/Th2 and that enhanced IL-4 production is correlated with enhanced CD86 expression in the gut. Therefore, LS is a functional food for patients with inflammatory bowel disease.