Inverse relationship between serum osteocalcin levels and nonalcoholic fatty liver disease in postmenopausal Chinese women with normal blood glucose levels.

AIM: Osteocalcin is involved in the progression of nonalcoholic fatty liver disease (NAFLD) in animal models and humans. In this study we investigated the relationship between serum osteocalcin levels and NAFLD in postmenopausal Chinese women. METHODS: A total of 733 postmenopausal women (age range: 41-78 years) with normal blood glucose levels were enrolled in this cross-sectional study. Women taking lipid-lowering or anti-hypertensive drugs were excluded. Serum osteocalcin levels were assessed using an electrochemiluminescence immunoassay. The degree of NAFLD progression for each subject was assessed through ultrasonography. The fatty liver index (FLI) of each subject was calculated to quantify the degree of liver steatosis. RESULTS: The median level of serum osteocalcin for all subjects enrolled was 21.99 ng/mL (interquartile range: 17.84-26.55 ng/mL). Subjects with NAFLD had significantly lower serum osteocalcin levels (18.39 ng/mL; range: 16.03-23.64 ng/mL) compared with those without NAFLD (22.31 ng/mL; range: 18.55-27.06 ng/mL; P<0.01). Serum osteocalcin levels decreased with incremental changes in the FLI value divided by the quartile (P-value for trend<0.01). The serum osteocalcin levels showed a negative correlation with the FLI values, even after adjusting for confounding factors (standardized ß=-0.124; P<0.01). Binary logistic regression analysis identified an individual's serum osteocalcin level as an independent risk factor for NAFLD (odds ratio: 0.951; 95% confidence interval: 0.911-0.992; P=0.02). CONCLUSION: Serum osteocalcin levels are inversely correlated with NAFLD in postmenopausal Chinese women with normal blood glucose levels.

Serum vitamin D is associated with non-alcoholic fatty liver disease in Chinese males with normal weight and liver enzymes.

AIM: Considering the characterization of vitamin D deficiency as a risk factor of ectopic fat deposition, the association of serum 25-hydroxy vitamin D3 [25(OH)D3] levels with non-alcoholic fatty liver disease (NAFLD) was evaluated in Chinese men with normal body mass index (BMI) and enzyme markers of liver function. METHODS: A total of 514 participants (22 to 79 years old) with normal BMI and liver enzymes were identified for analysis. Abdominal ultrasound was performed to diagnose NAFLD, and the fatty liver index (FLI) was calculated to quantify liver steatosis. Serum 25(OH)D3 levels were determined by an electrochemiluminescence immunoassay. RESULTS: Among the entire study population, the mean levels of serum 25(OH)D3 were 15.32±5.77 ng/mL. However, when serum 25(OH)D3 levels were compared between non-NAFLD subjects (n=438) and NAFLD subjects (n=76), the latter showed significantly lower levels (15.65±5.89 ng/mL vs 13.46±4.65 ng/mL, P=0.002). In addition, serum 25(OH)D3 levels were found to be significantly correlated with FLI after adjustment for age and BMI (r=-0.108, P=0.014). Logistic regression showed that serum 25(OH)D3 levels were independently correlated with NAFLD (OR: 0.937, 95% CI: 0.884-0.993, P=0.028). Furthermore, stepwise regression analysis revealed that serum 25(OH)D3 levels were inversely associated with FLI (ß=-0.055, P=0.040). CONCLUSION: The present study demonstrated that serum 25(OH)D3 levels were inversely associated with NAFLD, even in subjects with normal total body fat, suggesting a potential role of lower levels of vitamin D in the occurrence and development of NAFLD.

[Effect of L-Arginine on intestinal mucosal injury of rats with severe abdominal infection].

OBJECTIVE: To investigate the effect of L-Arginine on intestinal mucosal injury of rats with severe abdominal infection. METHODS: Rats received cecal ligation and puncture (CLP) to reproduce sepsis model. A total of 18 Wistar rats were divided into two groups randomly (each n=9): L-Arginine group and model group. Three hundred mg/kg of L-Arginine was injected into the abdomen in rats of L- Arginine group after CLP. Model group received equal volume of normal saline. Blood sample was harvested and the serum levels of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) were determined at 24 hours after operation in both groups. The histopathological change of intestinal mucosa was observed under light microscope and mucosa damage index was determined. RESULTS: The intestinal mucosal damage was observed both in model group and L- Arginine group after CLP, but the injury was milder in L- Arginine group. There was significant difference in mucosa injury index between L-Arginine group and model group (3.4+/-0.6 vs. 4.1+/-0.5, P<0.05). The serum level of NO [(76.1+/-26.2) micromol/L vs. (87.3+/-16.7) micromol/L, P>0.05] and iNOS [(30.6+/-7.4) U/L vs(44.4+/-6.6) U/L, P<0.01] in L-Arginine group were lower than those in model group. CONCLUSION: L-Arginine could protect against intestinal mucosal injury and depress the serum level of iNOS in severe abdominal infection of rats.

[Dynamic observation of intestinal epithelial stem cells of small intestine during the injured-repaired progress induced by 5-FU].

OBJECTIVE: To investigate the dynamic changes of intestinal epithelial stem cells during the injured-repaired progress induced by 5-FU. METHODS: Fifty adult C57BL/6J mice were enrolled in this study, 40 of them were intraperitoneally injected with 5-FU (30 mg per kg of body weigh) for five days, and 10 of them intraperitoneally injected with PBS as control. At day 1, 3, 5, 7 after treatment, the mice were killed and middle intestine was taken. Pathology was examined by HE staining. Musashi-1 (msi-1) expression was detected by immunohistochemical technique. The percentage of Rho low staining cells was detected by flow cytometry. RESULTS: After treatment with 5-FU, the intestinal mucosa was damaged. The Rho low staining cells were increasing, and at day 1 after treatment, the percentage of Rho low staining cells reached the highest level (P<0.01). The number of cells expressing msi-1 did not change significantly (P>0.05), but the percentage of positive msi-1 cells increased significantly (P<0.01). There was positive correlation between the percentage of Rhodamine 123 low staining cells and positive msi-1 cells in each group (r=0.867, P<0.01). CONCLUSIONS: The Rho low staining cells may contain rich intestinal epithelial stem cells. The intestinal epithelial stem cells expressing msi-1 can regenerate the damage of intestinal mucosa induced by 5-FU.

[Screening peptides binding specifically to large intestinal cancer LoVo cells from phage random peptide library].

OBJECTIVE: To screen the polypeptides specifically binding to human large intestinal cancer LoVo cells from a phage-displayed peptide library for potential use as targeting vectors for large intestinal cancer therapy. METHODS: With the LoVo cells as the target cells and human normal large intestinal mucosal epithelial cells as the absorber cells for subtraction biopanning from a c7c phage-display peptide library, the positive phage clones were identified by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence detection. The amino acid sequences of the identified peptides were deduced by DNA sequencing. RESULTS: After 3 rounds of screening, 5 positive phage clones showing specific binding to LoVo cells and containing conserved motif RPMP were obtained from the 20 randomly selected clones. CONCLUSION: Specific peptide against large intestinal cancer cells can be obtained from a phage-display peptide library for use as potential vectors for targeting therapy of large intestinal cancer.

[Expression of proliferating cell nuclear antigen in severely damaged small intestinal mucosa due to high-dose 5-FU exposure].

OBJECTIVE: To detect the expression of proliferating cell nuclear antigen (PCNA) in severely damaged intestinal mucosa due to high-dose 5-FU exposure. METHODS: Thirty-two adult C57BL/6J mice were subjected to daily intraperitoneal high-dose 5-FU injection at 150 mg/kg for 5 consecutive days, and on days 1, 3, and 5, the mice were sacrificed to obtain the small intestinal tissue for HE straining and immunohistochemistry for detecting PCNA expression. Another 8 mice with intraperitoneal PBS injection served as the control group. RESULTS: High-dose 5-FU exposure of the mice resulted in severe intestinal mucous damage, with complete destruction of the villi and crypts and significantly increased cells positive for PCNA expression (P<0.01). CONCLUSION: High-dose 5-FU treatment can significantly increase the PCNA index, and the cells expressing PCNA can be closely associated with regeneration of the severely damaged mucosa due to the exposure.