Background： Nontraumatic osteonecrosis of the femoral head （NONFH） is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its ...significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population. Methods： A nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging exalnination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein （HDL） and low-density lipoprotein （LDL） levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH. Results： NONFH was diagnosed in 218 subjects （0.725%） and the estimated NONFH cases were 8.12 million among Chinesepeople aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females （1.02% vs. 0.51%, x^2 = 24.997, P 〈 0.001 ）. Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents （0.85% vs. 0.61%,x^2= 5.847, P = 0.016）. Our multivariate regression analysis showed that high blood levels oftriglycerides, total cholesterol, LDL-cholesterol, and non-H DL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head. heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH. Conclusions： Our findings highlight that NONFH is a significantpublic health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk factors with atherosclerosis.
Intestinal mucus barrier dysfunction is closely involved in the pathogenesis of inflammatory bowel diseases (IBD). To investigate the protective effect and underlying mechanism of arctigenin, a ...phytoestrogen isolated from the fruits of Arctium lappa L., on the intestinal mucus barrier under colitis condition. The role of arctigenin on the intestinal mucus barrier and the apoptosis of goblet cells were examined by using both in vitro and in vivo assays. Arctigenin was demonstrated to promote the mucus secretion and maintain the integrity of mucus barrier, which might be achieved by an increase in the number of goblet cells via inhibiting apoptosis. Arctigenin selectively inhibited the mitochondrial pathway‐mediated apoptosis. Moreover, arctigenin elevated the protein level of prohibitin 1 (PHB1) through blocking the ubiquitination via activation of estrogen receptor β (ERβ) to competitively interact with PHB1 and disrupt the binding of tripartite motif 21 (TRIM21) with PHB1. ERβ knock down in the colons of mice with DSS‐induced colitis resulted in significant reduction of the protection of arctigenin and DPN against the mucosal barrier. Arctigenin can maintain the integrity of the mucus barrier by inhibiting the apoptosis of goblet cells through the ERβ/TRIM21/PHB1 pathway.
Aim
The aim of this study was to use a metabonomics approach to identify potential biomarkers of exhaled breath condensate (EBC) for predicting the prognosis of acute‐on‐chronic liver failure (ACLF).
...Methods
Using liquid chromatography mass spectrometry, EBC metabolites of ACLF patients surviving without liver transplantation (n = 57) and those with worse outcomes (n = 45), and controls (n = 15) were profiled from a specialized liver disease center in Beijing. The metabolites were used to identify candidate biomarkers, and the predicted performance of potential biomarkers was tested.
Results
Forty‐one metabolites, involving glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, and amino acid metabolism, as candidate biomarkers for discriminating the different outcomes of ACLF were selected. A prognostic model was constructed by a panel of four metabolites including phosphatidylinositol 20:4(5Z,8Z,11Z,14Z)/13:0, phosphatidyl ethanolamine (12:0/22:0), L‐metanephrine and ethylbenzene, which could predict the worse prognosis in ACLF patients with sensitivity (84.4%) and specificity (89.5%) (area under the receiver operating characteristic curve AUC = 0.859, 95% confidence interval CI = 0.787–0.931). Compared with Model for End‐Stage Liver Disease (MELD) score (AUC = 0.639, 95% CI = 0.526–0.753) and MELD‐sodium (MELD‐Na) score (AUC = 0.692, 95% CI = 0.582–0.803), EBC‐associated metabolite signature model could better predict worse outcomes in patients with ACLF (p < 0.05). Using the MELD‐Na score and EBC metabolite signatures, a decision tree model was built for predicting the prognosis of ACLF identified on logistic regression analyses (AUC = 0.906, 95% CI = 0.846–0.965).
Conclusion
EBC metabolic signatures show promise as potential biomarkers for predicting worse prognosis of ACLF.
Inhibition of immunocyte infiltration and activation has been suggested to effectively ameliorate nonalcoholic steatohepatitis (NASH). Paired immunoglobulin-like receptor B (PirB) and its human ...ortholog receptor, leukocyte immunoglobulin-like receptor B (LILRB2), are immune-inhibitory receptors. However, their role in NASH pathogenesis is still unclear. Here, we demonstrate that PirB/LILRB2 regulates the migration of macrophages during NASH by binding with its ligand angiopoietin-like protein 8 (ANGPTL8). Hepatocyte-specific ANGPTL8 knockout reduces MDM infiltration and resolves lipid accumulation and fibrosis progression in the livers of NASH mice. In addition, PirB
bone marrow (BM) chimeras abrogate ANGPTL8-induced MDM migration to the liver. And yet, PirB ectodomain protein could ameliorate NASH by sequestering ANGPTL8. Furthermore, LILRB2-ANGPTL8 binding-promoted MDM migration and inflammatory activation are also observed in human peripheral blood monocytes. Taken together, our findings reveal the role of PirB/LILRB2 in NASH pathogenesis and identify PirB/LILRB2-ANGPTL8 signaling as a potential target for the management or treatment of NASH.
•Structural characteristic of AERP is investigated by GC–MS, FT-IR, HPSEC-ELSD and colorimetric methods.•A small number of sulfate (3.38%) and acetyl (4.87%) groups were observed.•AERP showed potent ...hepatoprotective effects in vivo by CIALI in mice.•AERP displayed obvious effects on SCFAs produced by intestinal flora metabolism.
The structural characteristics of the polysaccharides from Aralia elata root barks (AERP) were systematically investigated by FT-IR, HPSEC-ELSD and colorimetric methods as well as by GCMS based monosaccharide compositions, Smith degradations, and methylation analysis. The result showed average molecular weights of AERP were between 42.7 kDa and 93.9 kDa. AERP was composed of Ara, Rha, GlcA, Man, Glc, and Gal in a molar ratio of 22.2: 10.3: 8.1: 32.7: 5.7: 21.2 along with a small number of sulfate (3.38%) and acetyl (4.87%) groups. The abundant glycosidic linkages of Man, Ara, Gal, and Rha were observed as more than 90% of all the monosaccharides detected. Studies to evaluate hepatoprotective potentials of AERP showed that they had potent hepatoprotective effects in vivo in carbon tetrachloride-induced acute liver injury (CIALI) in mice by histopathological evaluation, biochemical examinations and ELISA assays. GCMS was further used to determine the effects of AERP on the chemical profiles of nine common short-chain fatty acids (SCFAs) produced by intestinal flora metabolism in CIALI mice. These findings not only provide novel insights into the pharmacological actions of AERP on the protection from CIALI in mice, but they also demonstrate that determining SCFA profiles by targeted GC–MS metabolomics is an effective technique to investigate the molecular mechanisms of the effects of plant polysaccharides on intestinal flora metabolism.
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•The regulation mechanism of ASBT was summarized.•The relationship between ASBT and various diseases was discussed and the scope of diseases involved was expanded.•According to the ...chemical stucture classification, the application of ASBT inhibitors was summarized in detail.
Bile acids has gradually become a new focus in various diseases, and ASBT as a transporter responsible for the reabsorption of ileal bile acids, is a key hinge associated to the bile acids-cholesterol balance and bile acids of enterohepatic circulation. The cumulative studies have also shown that ASBT is a promising target for treatment of liver, gallbladder, intestinal and metabolic diseases. This article briefly reviewed the process of bile acids enterohepatic circulation, as well as the regulations of ASBT expression, covering transcription factors, nuclear receptors and gut microbiota. In addition, the relationship between ASBT and various diseases were discussed in this paper. According to the structural classification of ASBT inhibitors, the research status of ASBT inhibitors and potential ASBT inhibitors of traditional Chinese medicine (such resveratrol, jatrorrhizine in Coptis chinensis) were summarized. This review provides a basis for the development of ASBT inhibitors and the treatment strategy of related diseases.
Oral administration of curcumin has been shown to inhibit pulmonary fibrosis (PF) despite its extremely low bioavailability. In this study, we investigated the mechanisms underlying the anti-PF ...effect of curcumin in focus on intestinal endocrine. In bleomycin- and SiO
-treated mice, curcumin (75, 150 mg· kg
per day) exerted dose-dependent anti-PF effect when administered orally or rectally but not intravenously, implying an intestinal route was involved in the action of curcumin. We speculated that curcumin might promote the generation of gut-derived factors and the latter acted as a mediator subsequently entering the lungs to ameliorate fibrosis. We showed that oral administration of curcumin indeed significantly increased the expression of gut-derived hepatocyte growth factor (HGF) in colon tissues. Furthermore, in bleomycin-treated mice, the upregulated protein level of HGF in lungs by oral curcumin was highly correlated with its anti-PF effect, which was further confirmed by coadministration of c-Met inhibitor SU11274. Curcumin (5-40 μM) dose-dependently increased HGF expression in primary mouse fibroblasts, macrophages, CCD-18Co cells (fibroblast cell line), and RAW264.7 cells (monocyte-macrophage cell line), but not in primary colonic epithelial cells. In CCD-18Co cells and RAW264.7 cells, curcumin dose-dependently activated PPARγ and CREB, whereas PPARγ antagonist GW9662 (1 μM) or cAMP response element (CREB) inhibitor KG-501 (10 μM) significantly decreased the boosting effect of curcumin on HGF expression. Finally, we revealed that curcumin dose-dependently increased the production of 15-deoxy-Δ
-prostaglandin J2 (15d-PGJ2) in CCD-18Co cells and RAW264.7 cells, which was a common upstream of the two transcription factors. Moreover, both the in vitro and in vivo effects of curcumin were diminished by coadministration of HPGDS-inhibitor-1, an inhibitor of 15d-PGJ2 generation. Together, curcumin promotes the expression of HGF in colonic fibroblasts and macrophages by activating PPARγ and CREB via an induction of 15d-PGJ2, and the HGF enters the lungs giving rise to an anti-PF effect.
Lymphoid‐specific helicase (LSH) is overexpressed in tumor tissues and its overexpression is associated with poor prognosis in several cancers. However, the role and molecular mechanism of LSH in ...hepatocellular carcinoma (HCC) remains largely unknown. Herein, we report that LSH was overexpressed in tumor tissues of HCC, and overexpression of LSH was associated with poor prognosis from a public HCC database, and validated by clinical samples from our department. Ectopic LSH expression promoted the growth of HCC cells in vivo and in vitro. Mechanistically, LSH overexpression promoted tumor growth by activating transcription of centromere protein F (CENPF). Clinically, overexpression of LSH and/or CENPF correlated with shorter overall survival and higher cumulative recurrence rates of HCC. In conclusion, LSH promotes tumor growth of HCC through transcriptional regulation of CENPF expression. Therefore, LSH may be a novel predictor for prognosis and a potential therapeutic target for HCC.
In the present study, we first evaluated LSH as a potential prognostic marker in hepatocellular carcinoma. We also investigated the cellular and molecular mechanism, especially in cancer invasion and metastasis. Herein, we initially determined a novel mechanism involving protein‐DNA binding between LSH and the CENPF gene.
•Proposed a semi-analytic J-integral model with three-dimensional constraints.•Verified the accuracy of the proposed model using finite element analysis.•Determined the geometric independence of the ...proposed model.•Analyzed the influence of the constitutive parameters on the proposed model.•The proposed model is simple, accurate, and well-suited to engineering practice.
The J-integral is widely used in fracture analysis to characterize the stress-strain field at the crack tip. To describe the dimensionless relationships between the J-integral and the load for mode-I cracks in ductile materials, a novel model based on the energy density equivalence is proposed by introducing the three-dimensional constraint functions. The model-obtained relationships between the J-integral and the load are shown to be consistent with those obtained via finite element analysis. Moreover, the dimensionless relationships provided by the proposed model are shown to be only related to the constitutive parameters and independent of the geometric dimensions of mode-I cracks.
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