Effect of SCN1Aand SCN2A gene polymorphisms on the efficacy of valproic acid treatment in Chinese children with epilepsy.

OBJECTIVE: Epilepsy patients exhibit considerable differences in their response to sodium valproate (VPA) therapy, a phenomenon that might be attributed to individual genetic variances. The role of genetic variations, specifically in sodium channels encoded by SCN1A and SCN2A genes, in influencing the effectiveness of VPA in treating epilepsy is still debated. This research focuses on examining the impact of these genetic polymorphisms on the efficacy of VPA therapy among pediatric epilepsy patients in China. METHODS: Five single nucleotide polymorphisms (SNPs), including SCN1A (rs10188577, rs2298771, rs3812718) and SCN2A (rs2304016, rs17183814), were genotyped in 233 epilepsy patients undergoing VPA therapy. The associations between genotypes and the antiepileptic effects of VPA were assessed, with 128 patients categorized as VPA responders and 105 as VPA non-responders. RESULTS: In the context of VPA monotherapy, SCN1A rs2298771 and SCN2A rs17183814 were found to be significantly associated with VPA response (P< 0.05). CONCLUSION: Our study suggests the findings of this investigation indicate that the polymorphisms SCN1A rs2298771 and SCN2A rs17183814 could potentially act as predictive biomarkers for the responsiveness to VPA among Chinese epilepsy patients.

Semen hoveniae extract ameliorates alcohol-induced chronic liver damage in rats via modulation of the abnormalities of gut-liver axis.

BACKGROUND: Hovenia dulcis Thunb. is considered as a traditional herbal medicine that has been used in the treatment for ethanol-induced liver disease for centuries. Recently, substantial studies demonstrated that Semen hoveniae extract (SHE) not only suppressed the hepatic steatosis caused by chronic ethanol exposure, but also inhibited lipopolysaccharide-stimulated inflammatory responses. Nevertheless, the underlying molecular mechanisms largely remained elusive. AIM: To determine the hepatoprotective effects of SHE on ethanol-triggered liver damage and further elucidate its potential mechanisms. METHODS: In the present study, the Sprague-Dawley rats were fed with the Lieber-DeCarli diet containing alcohol or isocaloric maltose dextrin as control diet with or without SHE (300 and 600 mg/kg/d bw) for 8 weeks. The levels of serum biomarkers (ALT, AST and LDH) and LPS were detected by biochemical assay kits and endotoxin detection LAL kit, respectively. The histopathological changes of liver and intestinal tissues were observed by hematoxylin and eosin (H&E) staining and Transmission electron microscope (TEM). The expressions of CD14, TLR4, MyD88, NF-κB, Iκ-B, P-Iκ-B and TNF-α in liver, and ZO-1 and occludin in intestine were determined by western blot. The faecal microbial composition was determined by16S rRNA Gene Sequencing Analysis. RESULTS: Biochemical and histopathological analysis revealed that SHE significantly alleviated the lipid deposition and inflammation response in liver induced by ethanol. SHE remarkably inhibited the TLR4 pathway and its downstream inflammatory mediators, and up-regulated the expressions of ZO-1 and occludin in the intestine. The further investigations suggested SHE dramatically reversed ethanol-induced alterations in the intestinal microbial flora and decreased the generation of gut-derived endotoxin. CONCLUSION: In summary, SHE probably modulated abnormalities of gut-liver axis and inhibited TLR4-associated inflammatory mediators activation to exert its hepatoprotective properties. These findings suggested that SHE as a traditional therapeutic options which may play an essential role in protecting against the chronic ethanol-triggered liver injury.

[Advance in studies on food allergy mechanism based on gut barrier].

Food allergies, as a type of adverse immune-mediated reactions to ingested food proteins, have become a serious public health issue that harms children and adults health, with increasing incidence year by year. However, without effective therapy for food allergies, doctors-have mostly advised to avoid allergens and provided symptomatic treatment. According to the findings of many studies, allergic diseases are correlated with intestinal barrier function injury, as evidenced by the significant increase in the intestinal permeability among patients with food allergies. In this paper, recent studies on correlations between food allergies and intestinal barrier functions, intestinal barrier function injury mechanisms of allergic foods and food allergy intervention strategies based on intestinal barrier functions were summarized to provide reference for laboratory researches and clinical treatment of food allergic diseases.

[Intervention effect and mechanism of compound Ginkgo biloba preparations on nonalcoholic fatty liver].

OBJECTIVE: To investigate the intervention effect and mechanism of compound Ginkgo biloba (CGB) preparations on nonalcoholic fatty liver disease (NAFLD). METHOD: The C57BL/6 mouse NAFLD model was induced with high fat diets. Since the 2nd week after modeling, the mice were orally administered with 600 and 200 mg x kg(-1) x d(-1) CGB for eight weeks. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), cholesterol (CHOL) and LPS in serum, as well as pathological changes and expression of tumor necrosis factor-alpha (TNF-alpha) in hepatic tissues were observed. Changes in intestinal tight junction proteins ZO-1, Occludin, Claudin-1 in intestinal tissues were determined under microscopy. RESULT: Compared with the normal group, the model group showed obvious fatty degeneration in rat livers, with notable increase in TNF-alpha expression (P < 0.01), significant increases in ALT, AST, TG, CHOL and LPS in serum (P < 0.01, P < 0.05), injury in intestinal tight junction proteins, and remarkable declines in ZO-1, Occludin and Claudin-1 (P < 0.01). Compared with the model group, CGB high and low dose groups showed obvious relieves in fatty degeneration in rat livers and injury in intestinal tight junction proteins, significant reductions in TNF-alpha expression (P < 0.01, P < 0.05) and AST, TG, CHOL and LPS in serum (P < 0.01, P < 0.05) and remarkable increases in ZO-1 and Occludin expressions (P < 0.05). CONCLUSION: CGB can protect intestinal tight junction proteins, reduce intestinal leakage, relieve fatty degeneration and inflammations in livers and prevent NAFLD occurrence and development.

Herbal SGR Formula Prevents Acute Ethanol-Induced Liver Steatosis via Inhibition of Lipogenesis and Enhancement Fatty Acid Oxidation in Mice.

Our previous study indicated that herbal SGR formula partially attenuates ethanol-induced fatty liver, but the underlying mechanisms remain unclear. In the present study, mice were pretreated with SGR (100 and 200 mg/kg/d bw) for 30 d before being exposed to ethanol (4.8 g/kg bw). The biochemical indices and histopathological changes were examined to evaluate the protective effects and to explore potential mechanisms by investigating the adiponectin, tumor necrosis factor-α (TNF-α), peroxisome proliferators-activated receptor-α (PPAR-α), sterol regulatory element binding protein-1c (SREBP-1c), adenosine monophosphate-activated protein kinase (AMPK), and so forth. Results showed that SGR pretreatment markedly inhibited acute ethanol-induced liver steatosis, significantly reduced serum and hepatic triglyceride (TG) level, and improved classic histopathological changes. SGR suppressed the protein expression of hepatic SREBP-1c and TNF-α and increased adiponectin, PPAR-α, and AMPK phosphorylation in the liver. Meanwhile, acute toxicity tests showed that no death or toxic side effects within 14 days were observed upon oral administration of the extracts at a dose of 16 g/kg body wt. These results demonstrate that SGR could protect against acute alcohol-induced liver steatosis without any toxic side effects. Therefore, our studies provide novel molecular insights into the hepatoprotective effect of SGR formula, which may be exploited as a therapeutic agent for ethanol-induced hepatosteatosis.

Effects of compound Ginkgo biloba on intestinal permeability in rats with alcohol-induced liver injury.

This study aimed to investigate the effects of Compound Ginkgo biloba (CGB) on alterations in intestinal permeability and inflammation caused by endotoxin in chronic alcohol-induced liver injury. CGB was prepared by Ginkgo biloba extract and Rosa roxburghii in a 1 : 1 proportion. Rats were divided into four groups: control, ethanol, high-dosage CGB (0.6 g kg(-1) d(-1)) and low-dosage CGB (0.2 g kg(-1) d(-1)) group. Rats in the control group ingested a Lieber-DeCarli control liquid diet, while rats in the ethanol and CGB-treated groups ingested a Lieber-DeCarli alcohol liquid diet for eight weeks. CGB was orally administered from the beginning of the third week until the end of the experiment. CGB was observed to significantly reduce the activities of serum ALT, AST, diamine oxidase (DAO) as well as levels of serum TG, D-lactic acid and plasma endotoxin in rats fed with Lieber-DeCarli ethanol liquid. Further, the hepatic steatosis was improved and the damage to intestinal tight junctions was also relieved effectively after CGB administration. Moreover, CGB significantly downregulated the expressions of TNF-α, lipopolysaccharide binding protein (LBP), CD14 and TLR4 in the liver and upregulated the expressions of tight junction proteins including ZO-1, occludin and claudin-1. In summary, this study demonstrated that CGB alleviated alcohol-induced liver injury and hepatic lipopolysaccharide signaling as well as gut barrier dysfunction through restoring tight junctions.