Dietary cholesterol drives the development of nonalcoholic steatohepatitis by altering gut microbiota mediated bile acid metabolism in high-fat diet fed mice.

Nonalcoholic fatty liver disease (NAFLD) is the most widespread chronic liver disorder globally. Unraveling the pathogenesis of simple fatty liver to nonalcoholic steatohepatitis (NASH) has important clinical significance for improving the prognosis of NAFLD. Here, we explored the role of a high-fat diet alone or combined with high cholesterol in causing NASH progression. Our results demonstrated that high dietary cholesterol intakes accelerate the progression of spontaneous NAFLD and induces liver inflammation in mice. An elevation of hydrophobic unconjugated bile acids cholic acid (CA), deoxycholic acid (DCA), muricholic acid and chenodeoxycholic acid, was observed in high-fat and high-cholesterol diet fed mice. Full-length sequencing of the 16S rDNA gene of gut microbiota revealed a significant increase in the abundance of Bacteroides, Clostridium, and Lactobacillus that possess bile salt hydrolase activity. Furthermore, the relative abundance of these bacterial species was positively correlated with content of unconjugated bile acids in liver. Moreover, the expression of genes related to bile acid reabsorption (organic anion-transporting polypeptides, Na+-taurocholic acid cotransporting polypeptide, apical sodium dependent bile acid transporter and organic solute transporter ß) was found to be increased in mice with a high-cholesterol diet. Lastly, we observed that hydrophobic bile acids CA and DCA induce an inflammatory response in free fatty acids-induced steatotic HepG2 cells. In conclusion, high dietary cholesterol promotes the development of NASH by altering gut microbiota composition and abundance and thereby influencing with bile acid metabolism.

Deoxycholic Acid Promotes Pyroptosis in Free Fatty Acid-Induced Steatotic Hepatocytes by Inhibiting PINK1-Mediated Mitophagy.

Nonalcoholic steatohepatitis (NASH) is the inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), which can lead to liver fibrosis and cirrhosis. Bile acid levels are correlated with markers of hepatic injury in NASH, suggesting a possible role for bile acids in the progression of NAFLD. Here, we examined the role of deoxycholic acid (DCA) in driving steatotic hepatocytes to pyroptosis, a pro-inflammatory form of programmed cell death. HepG2 cells were stimulated with odium oleate and sodium palmitate for modeling steatotic hepatocytes and then treated with DCA alone or in combination with a specific mitophagy agonist, carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Our results showed that DCA dose-dependently induced a pro-inflammatory response in steatotic hepatocytes but had no significant effect on lipid accumulation. Moreover, activation of the NLRP3 inflammasome and pyroptosis were triggered by DCA. Expression levels of the mitophagy markers PTEN-induced kinase 1 (PINK1) and E3 ubiquitin ligase Parkin were significantly diminished by DCA, whereas induction of mitophagy by CCCP prevented DCA-induced inflammatory response and restored the pyroptosis. Collectively, our data showed that DCA-induced pyroptosis involves the inhibition of PINK1-mediated mitophagy and the activation of the NLRP3 inflammasome. These findings provide insight into the association of DCA with mitophagy, pyroptosis, and inflammation in NASH.

Antiaging Potential of Peptides from Underused Marine Bioresources.

Aging is a biological process that occurs under normal conditions and in several chronic degenerative diseases. Bioactive natural peptides have been shown to improve the effects of aging in cell and animal models and in clinical trials. However, few reports delve into the enormous diversity of peptides from marine organisms. This review provides recent information on the antiaging potential of bioactive peptides from underused marine resources, including examples that scavenge free radicals in vitro, inhibit cell apoptosis, prolong the lifespan of fruit flies and Caenorhabditis elegans, suppress aging in mice, and exert protective roles in aging humans. The underlying molecular mechanisms involved, such as upregulation of oxidase activity, inhibition of cell apoptosis and MMP-1 expression, restoring mitochondrial function, and regulating intestinal homeostasis, are also summarized. This work will help highlight the antiaging potential of peptides from underused marine organisms which could be used as antiaging foods and cosmetic ingredients in the near future.

The use of mind mapping in health education in extended care for children with caries.

OBJECTIVE: To investigate the application of mind mapping-based health education in extended care for children with caries. METHODS: This was a prospective study of 159 eligible children with caries. Participants were randomly assigned to an observation group and a control group, and received extended health education and guidance. Patients in the observation group received health education with mind mapping. In the third month after the first visit, a questionnaire survey was conducted to assess knowledge of extended caries diagnosis and treatment in children and their parents. Children also underwent a bacterial plaque test. RESULTS: Caries knowledge was significantly greater in the observation group than in the control group. There was no significant between-group difference in debris index on the bacterial plaque test. The observation group had a significantly greater number of follow-up visits in 12 months than the control group. CONCLUSIONS: Mind mapping was effective in the implementation of extended care. Mind mapping information was more accessible to children and their parents, increasing their compliance with health education. Thus, mind mapping is an appropriate health education tool for use in extended care for children with caries.

The effects of chronic lead exposure on the liver of female Japanese quail (Coturnix japonica): Histopathological damages, oxidative stress and AMP-activated protein kinase based lipid metabolism disorder.

Lead (Pb) is one of the most toxic metals to human and wildlife. It also had multiple negative influences on birds with physical, neurological and hematological clinical signs. However, the impacts of lead on bird liver lipid metabolism are still unclear. In this study, female Japanese quails were used to examine the effects of chronic lead exposure on liver histology, oxidative stress and AMPK (AMP-activated protein kinase) based lipid metabolism. Quails were randomly divided into 5 groups and each group was respectively fed with 0, 50, 250, 500 and 1000 ppm lead solution for 49 days. The result showed that exposure to 250, 500 and 1000 ppm Pb induced severe histopathological damages characterized by liver lipid vacuoles and accumulation, hepatic cytoplasmic hyalinization and vacuolization, hepatocytes necrosis, hepatic sinusoid congestion, and it also caused ultrastructural alterations featured by swelling and vacuolar mitochondria, the depolymerization of polyribosome, and lipid droplets accumulation. Moreover, significant decrease of activities of GPx (glutathione peroxidase), SOD (superoxide dismutase), CAT (catalase) and level of T-AOC (total antioxidant capacity) while significant increase of MDA (malondialdehyde) content were found in livers of all Pb groups. In addition, the expressions of genes related to fatty synthesis were significantly upregulated in livers of all Pb groups while the expressions of genes related to fatty ß-oxidation were significantly downregulated in livers of 250 ppm Pb group. The present study indicated lead exposure does cause bird health damages through inducing liver microstructural and ultrastructural injury, oxidative damages and lipid metabolism disorder.

Chronic lead exposure induces histopathological damage, microbiota dysbiosis and immune disorder in the cecum of female Japanese quails (Coturnix japonica).

Lead (Pb) is one of the most hazardous metals to human and wildlife and it also has multiple negative impacts on birds. However, its influences on bird gut morphology and intestinal microbiota were still unclear. We used female Japanese quails (Coturnix japonica) to examine the effects of chronic lead exposure (0, 50 ppm and 1000 ppm) on cecal histology, microbial communities and immune function. The results showed 50 ppm lead exposure caused subtle damages of cecum cell structure. However, 1000 ppm lead exposure caused severe cecum histopathological changes characterized by mucosa abscission, Lieberkühn glands destruction and lymphocyte proliferation. Moreover, both lead concentrations induced ultrastructural damages featured by nucleus pyknosis, mitochondrial vacuolation and microvilli contraction. Meanwhile, microbial community structure, species diversity, taxonomic compositions and taxa abundance in the cecum were affected by lead exposure. Furthermore, the mRNA relative expression of immunity-related genes such as interleukin 2 (IL-2) and gamma interferon (IFN-γ) was significantly downregulated while that of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and natural killer kappa B (NF-κB) was significantly upregulated in the cecum of 50 and 1000 ppm lead exposure groups. We concluded that lead exposure may cause gut health impairment of female Japanese quails by inducing cecal histopathological changes, microbiota dysbiosis and cecal immune disorder.

Breeding habitat survey of blackthroat (Luscinia obscura) in Foping nature reserve of Qinling Mountains.

We carried out a primary survey by quadrat sampling to quantify breeding habitat characteristics of blackthroat (Luscnia obscura), a poorly documented and vulnerable bird species, in Foping nature reserve on the central southern Qinling Mountains. Tree layer information was collected in 10 m × 10 m plots, bamboo and shrub layer information was collected in 2 m × 2 m plots, and grass and ground layer information was collected in 1 m × 1 m plots. Our observations showed that blackthroat lives in coniferous forest and coniferous broadleaved forest with dense bamboos at the elevation ranging from 2130 m to 2600 m. Shrub cover, density and height, and ground cover in sites with blackthroat were significantly higher than those in random sites, while tree density, grass height and cover in habitat sites were significantly lower than those in random sites. These results suggest that shrub cover, shrub density, and canopy cover may be relevant to breeding habitat selection by these birds. Our study suggests that Qinling Mountains may be an important blackthroat breeding site.

An unstructured phylogeographic pattern with extensive gene flow in an endemic bird of South China: collared Finchbill (Spizixos semitorques).

Recent phylogeographical studies indicated that glacial oscillations played a key role on the phylogeographic pattern of extant species. As most studies have previously been carried out on heavily ice-covered regions, such as in European and North American regions, potential effects of climatic oscillations on species that are distributed on ice-free regions are less known. To address this, we investigated the phylogeographic pattern of an avian species endemic to South China, which was not glaciated during the Pleistocene glaciations. By using 2142 bp mitochondrial DNA, we identified 89 haplotypes defined by 39 polymorphic sites. A combination of high haplotype diversity (0.786-1.00) and low nucleotide diversity (0.00132-0.00252) was detected among geographic populations. Explicit genetic divergence was observed between S. s. semitorques and S. s. cinereicapillus but not detected among geographic populations of S. s. semitorques. Divergence time of the two subspecies was dated back to 87 Kyr which is congruent with the interglacial MIS 5. A weak phylogeographic structure due to strong gene flow among geographic populations was identified in this species, suggesting complex topography of South China has not formed barriers for this species.

The survey of H5N1 flu virus in wild birds in 14 Provinces of China from 2004 to 2007.

BACKGROUND: The highly pathogenic H5N1 avian influenza emerged in the year 1996 in Asia, and has spread to Europe and Africa recently. At present, effective monitoring and data analysis of H5N1 are not sufficient in Chinese mainland. METHODOLOGY/PRINCIPAL FINDINGS: During the period from April of 2004 to August of 2007, we collected 14,472 wild bird samples covering 56 species of 10 orders in 14 provinces of China and monitored the prevalence of flu virus based on RT-PCR specific for H5N1 subtype. The 149 positive samples involved six orders. Anseriformes had the highest prevalence while Passeriformes had the lowest prevalence (2.70% versus 0.36%). Among the 24 positive species, mallard (Anas platyrhynchos) had the highest prevalence (4.37%). A difference of prevalence was found among 14 provinces. Qinghai had a higher prevalence than the other 13 provinces combined (3.88% versus 0.43%). The prevalence in three species in Qinghai province (Pintail (Anas acuta), Mallard (Anas platyrhynchos) and Tufted Duck (Aythya fuligula)) were obviously higher than those in other 13 provinces. The results of sequence analysis indicated that the 17 strains isolated from wild birds were distributed in five clades (2.3.1, 2.2, 2.5, 6, and 7), which suggested that genetic diversity existed among H5N1 viruses isolated from wild birds. The five isolates from Qinghai came from one clade (2.2) and had a short evolutionary distance with the isolates obtained from Qinghai in the year 2005. CONCLUSIONS/SIGNIFICANCE: We have measured the prevalence of H5N1 virus in 56 species of wild birds in 14 provinces of China. Continuous monitoring in the field should be carried out to know whether H5N1 virus can be maintained by wild birds.