Gut microbiota dysbiosis and intestinal barrier impairment in diarrhea caused by cold drink and high-fat diet.

Cold drink and high-fat diet (CDHFD) are common diet patterns. However, the potential risks remain unclear. We investigated the effects of CDHFD in adult mice and explored the mechanisms of action. Twenty adult male mice were randomly divided into control and model groups, and the control group was fed a normal diet, whereas the model group was fed CDHFD for 28 days. We found that mice in the model group developed diarrhea symptoms accompanied by fatigue and weakness. Analysis of the intestinal flora revealed that the model group had a lower diversity and richness of microorganism species in the gut than the control group. Furthermore, the characteristic analysis indicated that CDHFD downregulated specific bacteria, such as norank_f_Muribaculaceae, Muribaculum, and Odoribacter, which are known to be associated with the systemic inflammatory response and mucosal barrier function. Blood tests showed that immune cells and inflammatory cytokines were significantly elevated in the model group, along with increased LPS induced by CDHFD. Pathological investigations demonstrated that CDHFD damages the intestinal mucosa while affecting the expression of tight junction proteins, including ZO-1, Claudin-1, Claudin-2, and Occludin, which may be attributed to the activation of the TRAF6/IκB/p65 signaling pathway. In conclusion, impaired gut microbial and mechanical barrier function is responsible for CDHFD-induced diarrhea. In this study, we constructed a model of diet-induced diarrhea by simulating human dietary patterns, evaluated the long-term effects of CDHFD on human intestinal barriers and immune systems, and revealed its mechanism of action based on chronic inflammation. This study validated the model's fit to provide an effective screening model for drug or functional food development.

Polymethoxyflavones in citrus extract has a beneficial effect on hypercholesterolemia rats by promoting liver cholesterol metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperlipidemia is characterized by the disorder of lipid metabolism accompanied by oxidative stress damage, and low-grade inflammation, with the pathway of cholesterol and bile acid metabolic are an important triggering mechanism. Polymethoxyflavones (PMFs) are the active constituents of Aurantii Fructus Immaturus, which have many biological effects, including anti-inflammatory, antioxidant activities, anti-obesity, suppressing adipogenesis in adipocytes, and ameliorate type 2 diabetes, with potential roles for regulation of lipid metabolism. However, its associated mechanisms on hyperlipidemia remain unclear. AIM OF THE STUDY: This study aims to identify the anti-hypercholesterolemia effects and mechanisms of PMFs in a hypercholesterolemia model triggered by high-fat compounds in an excessive alcohol diet (HFD). MATERIALS AND METHODS: A hypercholesterolemia rat model was induced by HFD, and PMFs was intragastric administered at 125 and 250 mg/kg daily for 16 weeks. The effects of PMFs on hypercholesterolemia were assessed using serum lipids, inflammatory cytokines, and oxidative stress levels. Hematoxylin & eosin (H&E) and Oil Red O staining were performed to evaluate histopathological changes in the rat liver. The levels of total cholesterol (TC) and total bile acid (TBA) in the liver and feces were determined to evaluate lipid metabolism. RAW264.7 and BRL cells loaded with NBD-cholesterol were used to simulate the reverse cholesterol transport (RCT) process in vitro. The signaling pathway of cholesterol and bile acid metabolic was evaluated by Western Blotting (WB) and qRT-PCR. RESULTS: Lipid metabolism disorders, oxidative stress injury, and low-grade inflammation in model rats were ameliorated by PMFs administration. Numerous vacuoles and lipid droplets in hepatocytes were markedly reduced. In vitro experiments results revealed decreased NBD-cholesterol levels in RAW264.7 cells and increased NBD-cholesterol levels in BRL cells following PMFs intervention. PMFs upregulated the expression of proteins associated with the RCT pathway, such as LXRα, ABCA1, LDLR, and SR-BI, thereby promoting TC entry into the liver. Meanwhile, the expression of proteins associated with cholesterol metabolism and efflux pathways such as CYP7A1, CYP27A1, CYP7B1, ABCG5/8, ABCB1, and BSEP were regulated, thereby promoting cholesterol metabolism. Moreover, PMFs treatment regulated the expression of proteins related to the pathway of enterohepatic circulation of bile acids, such as ASBT, OSTα, NTCP, FXR, FGF15, and FGFR4, thereby maintaining lipid metabolism. CONCLUSIONS: PMFs might ameliorate hypercholesterolemia by promoting the entry of cholesterol into the liver through the RCT pathway, followed by excretion via metabolism pathways of cholesterol and bile acid. These findings provide a promising therapeutic potential for PMFs to treat hypercholesterolemia.

Investigation and analysis on an outbreak of norovirus infection in a health school in Guangdong Province, China.

Our objective was to describe the epidemiological features of an outbreak of norovirus infection in a health school in Guangdong province, China, to identify the cause of such a large scale outbreak of norovirus among older students, to simulate the transmission dynamics, and to evaluate the effect of intervention measures of GII.17 [P17] genotype norovirus infection. We identified all cases during the outbreak. Descriptive epidemiological, analytical epidemiological and hygiene survey methods were used to described the outbreak epidemic course and identify the cause of the outbreak of norovirus infection. We also used dynamical model to simulate the transmission dynamics of norovirus infection and evaluate the effect of intervention measures. Norovirus genotyping was assigned to the newly obtained strains, with a maximum likelihood phylogenetic analysis conducted. There were 360 cases of 42 classes in five grades with a 12.99% attack rate. Proportionally, more students were in contact with sick students and vomit in the suspected case group than the control group (χ2 = 5.535, P = 0.019 and χ2 = 5.549, P = 0.019, respectively). The basic reproduction number was 8.32 before and 0.49 after the intervention. Dynamical modeling showed that if the isolation rate was higher or case isolation began earlier, the total attack rate would decrease. Molecular characterization identified the GII.17 [P17] genotype in all stains obtained from the health school, which were clustered with high support in the phylogenetic tree. This was an outbreak of norovirus infection caused by contact transmission. The main reasons for the spread of the epidemic were the later control time, irregular treatment of vomit and no case isolation. The transmission dynamics of contact transmission was high, more efficient control measures should be employed.

Network Pharmacology Prediction and Pharmacological Verification Mechanism of Yeju Jiangya Decoction on Hypertension.

BACKGROUND: Yeju Jiangya decoction (CIF) is an herbal formula from traditional Chinese medicine (TCM) for the treatment of hypertension. MATERIALS AND METHODS: Based on the analysis of network pharmacology, combined with in animal experiments, the network pharmacology was used to explore the potential proteins and mechanisms of CIF against hypertension. The bioactive compounds of CIF were screened by using the platform, and the targets of hypertension and CIF were collected. Then, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction network (PPI) core targets were carried out, and the useful proteins were found by molecular docking technology. Finally, we used N-nitro-L-arginine (L-NNA) induced hypertension model rats to confirm the effect and mechanism of CIF on hypertension. RESULTS: 14 bioactive compounds of CIF passed the virtual screening criteria, and 178 overlapping targets were identified as core targets of CIF against hypertension. The CIF-related target network with 178 nodes and 344 edges is constructed. The topological results show that quercetin and luteolin are the key components in the network. The key targets NOS3 (nitric oxide synthase 3) and NOS2 (nitric oxide synthase 2) were screened by the protein-protein interaction network. The analysis of target protein pathway enrichment showed that the accumulation pathway is related to the vascular structure of CIF regulation of hypertension. Further verification based on molecular docking results showed that NOS3 had the good binding ability with quercetin and luteolin. On the other hand, NOS3 has an important relationship with the composition of blood vessels. Furthermore, the animal experiment indicated that after the L-NNA-induced hypertension rat model was established, CIF intervention was given by gavage for 3 weeks, and it can decrease serum concentrations of endothelin-1 (ET-1) and thromboxane B2 (TXB2), increase the expression of nitric oxide (NO) and prostacyclin 2 (PGI2), and improve renal, cardiac, and aortic lesions. At the same time, it can reduce blood pressure and shorten vertigo time. Western blot (WB) and immunohistochemistry (IHC) analyses indicated that CIF may downregulate the expression of NOS3, guanylyl cyclase-alpha 1 (GC-α1), guanylyl cyclase-alpha 2 (GC-α2), and protein kinase CGMP-dependent 1 (PRKG1). These results suggest that CIF may play an antihypertensive role by inhibiting the activation of the NOS3/PRKG1 pathway. CONCLUSIONS: The results of this study indicate that CIF has the ability to improve target organs, protect endothelial function, and reduce blood pressure and that CIF might be a potential therapeutic drug for the prevention of hypertension. It provides new insight into hypertension and the potential biological basis and mechanism for CIF clinical research.

[Effect of Dendrobium officinale superfine powder on stomach Yin deficiency model mice induced by "spicy overeating"].

Dendrobium officinale is a traditional Chinese medicine for nourishing Yin and benefiting stomach. Its superfine powder has many advantages, such as good dissolution, high utilization rate, strong integrity and easy to use. However, the researches on effect of D. officinale superfine powder on stomach Yin deficiency model are still not sufficient. In this experiment, we explored the effect of D. officinale superfine powder in mice model with stomach Yin deficiency caused by "spicy overeating", and provided certain reference value for its application in gastrointestinal diseases. Male ICR mice were randomly divided into normal group, model group, Yiweitang group, omeprazole group, and D. officinale superfine powder high, medium and low dose groups. The mixture of wine and pepper liquid was given by gavage administration for 30 d, and the corresponding drug was given for 60 d while the model was conti-nued. The body weight, food intake, water intake, fecal moisture content and particle number, foot temperature of mice were measured. The levels of serum gastrin(Gas), motilin(MTL) and somatostatin(SS) were measured by ELISA. Gastric histomorpho-logy was observed by HE staining. The expression levels of nuclear factor kappa B(NF-κB) and cyclooxygenase-2(COX-2) were determined by immunohistochemistry. The expression levels of B-cell lymphoma-2(Bcl-2) and Bcl-2 associated X protein(Bax) in gastric tissues were detected by Western blot. The results showed that D. officinale superfine powder could increase the food intake, water intake, fecal moisture content and particle number, reduce the foot temperature, improve the pathological changes of gastric mucosa, reduce the expression of NF-κB, COX-2 protein in gastric tissues, and increase the ratio of Bax/Bcl-2. D. officinale superfine powder can "nourish Yin and benefit the stomach", improve the syndrome of stomach Yin deficiency, such as "hunger but not want to eat, dry mouth but not want to drink, hand and feet hot, constipation", and reduce the damage of gastric mucosa. The mechanism may be related to regulating the secretion of gastrointestinal hormones, inhibiting the inflammation of gastric tissues and promoting the apoptosis of abnormal cells in gastric tissues.

[Improvement effect and mechanism of ethanol extract from Citri Reticulatae Pericarpium on triglyceride in hyperlipidemia model rat].

The aim of this paper was to study the improvement effect of ethanol extract from Citri Reticulatae Pericarpium(CRP) on triglyceride of hyperlipidemia model rats, and to explore the possible mechanism. SD rats were randomly divided into normal group, model group, positive control group, and high, medium and low-dose CRP ethanol extract groups, with 10 rats in each group. During the experiment, except for the normal group that was fed with distilled water and ordinary feed, rats in the other groups were given different concentrations of alcohol and fed with high-sugar and fat diets. All rats were given free diets. While being modeled, each group was administered with 0.01 mL·g~(-1) by gavage once a day for six weeks. Blood samples were collected after two weeks, four weeks and six weeks of drug treatment. After the completion of the experiment, blood, liver and adipose tissue were collected. Triglyceride(TG), alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP) in serum, TG in liver tissue and TG in fecal were detected. Free fatty acid(FFA) and triglyceride-related hydrolase, such as adipose tiglyceride lipase(ATGL), lipoprotein lipase(LPL), hepatic lipase(HL), hormone-sensitive triglyceride lipase(HSL) were detected by ELISA. The mRNA expressions of peroxisome proliferators-activated receptors(PPARγ), sterol regulatory element binding protein 1 c(SREBP-1 c) and farnesoid X receptor(FXR) were determined by RT-PCR. Compared with the model group, each administration group could reduce TG levels in serum and liver to varying degrees, reduce serum ALT, AST, ALP activities, significantly reduce free fatty acid content in serum, significantly increase triglyceride metabolism-related enzymes, including fat ATGL, LPL and liver HL content, and significantly reduced the content of fat HSL. According to the study of transcriptional regulation genes relating to triglyceride metabolism, extract from CRP could significantly increase the mRNA expressions of PPARγ and FXR. In conclusion, ethanol extract from CRP could ob-viously reduce the TG level of hyperlipidemia model rats, and might reduce plasma TG content by increasing PPARγ-LPL/ATGL and FXR-HL triglyceride hydrolysis pathways.

Item selection in the development of quality of life scale for nasopharyngeal carcinoma patients.

BACKGROUND AND OBJECTIVE: At present, the quality of life (QOL) of nasopharyngeal carcinoma (NPC) patients is assessed with the QOL scales for cancer patients or head and neck cancer patients (QLQ-C30, QLQ-H&N35, and so on), and SF-36 scale, but they are not specific scales for NPC patients. The specific scale for NPC patients (Scale of Quality of Life for Nasopharyngeal Carcinoma, SQOL-NPC) has not been updated. This study was to develop a QOL scale (Quality of Life for Nasopharyngeal Carcinoma, QOL-NPC) for NPC patients in China. METHODS: The pilot scale was formed according to the definition of QOL from WHO and based on interviews with some experts and patients. The data were collected from 433 NPC patients treated in Cancer Center of Sun Yat-sen University from January to February, 2007. The items were preliminarily screened, evaluated, and modified, then selected by the methods of coefficient of variation, correlation analysis, factor analysis, and reliability analysis (the internal consistency Cronbach's coefficients). RESULTS: QOL-NPC was developed and evaluated. The scale included 30 items in four domains: physical function (PH), psychological function (PS), social function (SF), and side effect (SE). CONCLUSION: The QOL-NPC scale might be an effective scale for NPC patients because it is consistent with the WHO definition and connotation of QOL, and contains common issues of NPC patients as well.