Hesperetin derivative decreases CCl4 -induced hepatic fibrosis by Ptch1-dependent mechanisms.

Hepatic fibrosis (HF), a continuous wound-healing response of the liver to repeated injuries, is characterized by abnormal extracellular matrix (ECM) accumulation. Hepatic stellate cells (HSCs) are considered a major cell type for ECM production. However, recent evidence indicates the lack of effective treatments for HF. Hesperetin, a Traditional Chinese Medicine monomer, has been isolated from the fruit peel of Citrusaurantium L. (Rutaceae). Growing evidence suggests the partial function of hesperetin in HF treatment. A hesperetin derivative (HD) was synthesized in our laboratory to increase the bioavailability and the water solubility of hesperetin. In this study, we detected the functions of HD in a mouse model of CCl4 -induced HF and transforming growth factor-ß1-stimulated HSC-T6 cells, in vivo and in vitro. HD reduced histological damage and CCl4 -induced HF. Moreover, HD interference was associated with the activation of indicators in HSC-T6 cells, showing that HD is involved in HSCs activation in HF. Mechanistically, the Hedgehog pathway is involved in the HD treatment of HF, and HD may attenuate the aberrant expression of patched1. In conclusion, the studies indicate that HD may function as a potential antifibrotic Traditional Chinese Medicine monomer in HF therapy.

Hesperetin derivative attenuates CCl4-induced hepatic fibrosis and inflammation by Gli-1-dependent mechanisms.

Hepatic fibrosis, a common pathological feature and leading cause of various chronic liver diseases, still lacks effective therapy. Hesperetin derivative (HD) is a derivative of Traditional Chinese Medicine monomer isolated from the fruit peel of Citrusaurantium L. (Rutaceae). In the present study, we revealed the anti-fibrotic effects of HD in CCl4-induced mouse hepatic fibrosis model and in TGF-ß1-activated LX-2 cells, in vivo and in vitro. Results showed that HD prevented CCl4-induced liver injury and histological damage. Consistently, HD inhibited the up-regulation of liver fibrogenesis markers α-SMA, Col1α1, Col3α1 and TIMP-1 in primary hepatic stellate cells (HSCs) and suppressed inflammatory responses in primary liver macrophages from hepatic fibrosis mice. Furthermore, HD promoted the apoptosis of activated HSCs, a key step in the onset of fibrosis regression. Mechanistically, the Hedgehog pathway was involved in HD-treated hepatic fibrosis, and HD specifically contributed to attenuate the aberrant expression of Glioma associated oncogene-1 (Gli-1). Interestingly, blockade of Gli-1 removed the inhibitory effect of HD on activated HSCs, indicating that Gli-1 may play a pivotal role in mediating the anti-fibrotic effect of HD in hepatic fibrosis. Collectively, our results suggest that HD may be a potential anti-fibrotic Traditional Chinese Medicine monomer for the treatment of hepatic fibrosis.

Effects of Postoperative Parenteral Nutrition Enhanced by Multivitamin on Metabolic Phenotype in Postoperative Gastric Cancer Patients.

SCOPE: To investigate the effects of postoperative parenteral nutrition (PN) with multivitamins supplementation on oxidative stress and metabolism. METHODS AND RESULTS: The participants are randomly assigned in a 1:1 ratio to groups: total nutrient admixture (TNA) + multivitamin (n = 14, Group A) and TNA + normal saline (n = 16, Group B). The levels of blood vitamins, ILs, and MDA are assessed and the dysregulation of metabolism is analyzed using nontargeted metabolite profiling. The degree of postoperative stress in Group A is significantly lower than that in Group B by analyzing changes in the levels of IL-8 and MDA. A set of 43 features are qualified to have a variable importance parameter score of >1.5 of a partial least-squares discriminate analysis model and fold change of >1.5 at p-value <0.05 between Groups A and B. The principal metabolic alternations in Group A include increased tricarboxylic acid cycle and ketogenesis with reduced plasma-free amino acids. Backing the results of clinical biomarkers, increased levels of antioxidative molecules, together with decreased levels of inflammatory related polyunsaturated fatty acids, are observed. CONCLUSION: Postoperative PN enhanced by multivitamins can alleviate traumatic stress and improve metabolic transition from catabolism to anabolism in gastric cancer patients.

Investigation into knowledge, attitude, and practice regarding medical nutrition therapy among patients with diabetes in China: Results from a national multicenter cross-sectional study.

BACKGROUND: The aim of the present study was to investigate knowledge, attitude, and practice (KAP) associated with medical nutrition therapy (MNT) among Chinese adult patients with diabetes and prediabetes. METHODS: From May to August 2014, a cross-sectional study was conducted in 40 hospitals across China. The KAP of respondents was investigated through a pretested structured questionnaire in face-to-face interviews. Anthropometric and biochemical data were collected, and KAP scores were recorded according to patient responses. RESULTS: In all, responses from 7017 of 7508 patients were analyzed. The mean (±SD) overall KAP score was 9.63 ± 3.46, with individual scores for the K, A, and P components being 2.69 ± 1.90, 1.77 ± 1.99, and 5.17 ± 1.99, respectively (out of possible total scores of 19, 6, 3, and 10, respectively). All scores were higher in respondents who received ≥15 min MNT education than in those with shorter sessions. Patients with higher KAP scores exhibited significantly better glycemic control, with a higher proportion achieving target HbA1c, fasting plasma glucose, and 2-h postprandial blood glucose levels (P < 0.05). "Health publicity in hospitals" and "expert outpatient services" were the most favorable means of acquiring MNT information. The two predominant concerns associated with MNT were "the feasibility" and "the authenticity and professionalism of the information". CONCLUSIONS: Patients with diabetes and prediabetes achieved moderate scores for KAP towards MNT. Glycemic control was positively correlated with the KAP score. Thus, MNT education should be improved, with a particular focus on feasibility and authenticity and professionalism, in China.

Urinary neutrophil gelatinase-associated lipocalin: A potential biomarker for predicting rapid progression of drug-induced chronic tubulointerstitial nephritis.

INTRODUCTION: The role of urinary biomarkers of kidney injury in the prediction of adverse clinical outcomes in drug-induced chronic tubulointerstitial nephritis (D-CTIN) has not been well described. METHODS: A total of 36 patients with D-CTIN were enrolled in the study. The baseline urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL), alpha1-microglobin (alpha1-MG), albumin (mAlb) and total protein were measured, and estimated glomerular filtration rate change rates within a period of 6 to 33 (mean: 24 months) follow-up months were recorded. RESULTS: Areas under the receiver-operator characteristic curve of urinary NGAL, alpha1-MG, mAlb and total protein for predicting deterioration of estimated glomerular filtration rate were 0.707, 0.631, 0.685 and 0.678, respectively. The cutoff points that maximized the combined sensitivity and specificity for NGAL, alpha1-MG, mAlb and total protein were 37.71 ng/mL, 33.20 microg/mL, 6.91 mg/L and 60.00 mg/L, respectively. At these thresholds, the sensitivity and specificity was 64.7% and 78.9% for NGAL, 66.7% and 50.0% for alpha1-MG, 80.0% and 50.0% for mAlb and 70.6% and 63.2% for total protein, respectively. The median renal survival time (years) of patients with urinary NGAL level exceeding 37.705 ng/mL was shorter than that of patients with urinary NGAL level below 37.705 ng/mL (1.59 +/- 0.79 versus 2.09 +/- 0.63, P = 0.040, chi(2) = 4.218). CONCLUSIONS: Increase of baseline urinary NGAL was better than alpha1-MG, mAlb and total protein in predicting renal function deterioration in patients with D-CTIN. This noninvasive approach has potential to serve as a practical tool in D-CTIN prognosis.