Mechanism of Non-alcoholic Steatohepatitis Improved by Qizhu Prescription Based on AMPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effect and mechanism of Qizhu prescription on liver lipid anabolism and oxidative stress in mice with non-alcoholic steatohepatitis （NASH） based on adenylate activated protein kinase （AMPK） signaling pathway. MethodA total of 60 male C57BL/6J mice were randomly divided into a normal group （n = 10） and a modeling group （n = 50）. The modeling group was fed by high-fat and high-cholesterol diet for 16 weeks to establish the NASH mice model and was randomly divided into model group， low-， medium， and high-dose groups of Qizhu prescription， and Yishanfu group， with 10 mice in each group. Qizhu prescription was administered intragastrically once a day at a dose of 4.75， 9.50， and 19.00 g·kg-1 in each group and 228 mg·kg-1 in Yishanfu group. The normal group and model group were given equal volumes of pure water for eight weeks. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total cholesterol （TC）， triglyceride （TG）， and glucose （GLU） levels were detected. The pathological changes of liver tissue were observed by hematoxylin-eosin （HE） and oil red O staining. Serum levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， free fatty acids （FFA）， reduced glutathione （GSH）， malondialdehyde （MDA）， catalase （CAT）， and superoxide dismutase （SOD） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of acetyl-CoA carboxylase （ACC）， carnitine palmitoyl transferase 1A（CPT1A）， and mitochondrial uncoupling protein 2 （UCP2） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Protein expression levels of AMPK， p-AMPK， ACC， CPT1A， and UCP2 in liver tissue were detected by Western blot. ResultCompared with the normal group， the liver steatosis of the model group was obvious， with multiple inflammatory clusters and large amounts of intracellular lipid deposition. The activity of serum AST， ALT， as well as levels of IL-6， IL-1β， TNF-α， FFA， and MDA were significantly increased， the activity of CAT and SOD was significantly decreased， and the mRNA and protein expressions of ACC were significantly increased. The mRNA and protein expressions of CPT1 and UCP2 were significantly decreased， and the protein expression of p-AMPK was significantly decreased （P<0.01）. Compared with the model group， the degree of liver steatosis in the Qizhu prescription and Yishanfu groups was reduced， the activity of AST and ALT， as well as the levels of IL-6， IL-1β， TNF-α， FFA， and MDA was significantly decreased， and the activity of CAT and SOD was significantly increased （P<0.01）. The mRNA and protein expressions of ACC in liver tissue of mice in medium- and high-dose groups of Qizhu prescription were significantly decreased， while the mRNA and protein expressions of CPT1A and UCP2， as well as p-AMPK protein were significantly increased （P<0.01）. ConclusionQizhu prescription can improve liver lipid metabolism， reduce oxidative stress， and promote liver cell repair in NASH mice by activating the AMPK signaling pathway.

Advance in mechanism and application of antibacterial peptide / 中国生化药物杂志

In the era of outbreaking of antibiotic resistance, the discovery of new antibacterial drugs is emergent.Antimicrobial peptides are important components of the natural defenses of most living organisms against invading pathogens.The unique antibacterial mechanism, direct bactericidal effect, relatively slow of resistance acquirement, and can used alone or combined with antibiotics, make antimicrobial peptides be attractive potential antibacterial drugs.In this paper, we review the physicochemical property of antibacterial peptides, action mechanism and design of antimicrobial peptides, and give a brief introduction of several promising antimicrobial peptides.

Methodology and clinical significance of detecting EGFR-T790M mutation in advanced non-small cell lung cancer / 中国肿瘤临床

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) comprise an effective therapy for advanced non-small cell lung cancer patients with EGFR-activating mutations. Unfortunately, most patients eventually develop resistance to EG-FR-TKIs, probably due to a secondary point mutation of EGFR T790M. Thus, a sensitive method for accurate detection of T790M mu-tation is essential. Peripheral blood detection has gained our attention because it is convenient, making dynamic noninvasive quantita-tive detection of T790M mutation an optimal means of monitoring the efficacy of EGFR-TKIs. To date, the clinical significance of T790M mutation and EGFR-TKI resistance remains controversial. Several EGFR-TKIs targeting EGFR mutation, which have been in-troduced in recent years, showed better response in patients with T790M mutation, indicating that T790M may be a biomarker for con-quering resistance. This review introduces the methodology of T790M detection and its role in clinical practice.