Study on Periplaneta americana Polypeptide PAE2 in Reversing Multidrug Resistance for Liver Cancer / 中国实验方剂学杂志

Objective:To investigate the effect and mechanism of PAE₂， a polypeptide of <italic>Periplaneta americana， </italic>in reversing multidrug resistance （MDR） for liver cancer <italic>in vivo</italic>. Method:Balb/c-nude mice were inoculated with HepG2 and HepG2/ADM cells under the armpits to establish animal models of liver cancer sensitive strains and animal models of MDR respectively. After successful modeling， the nude mice were randomly divided into normal group， HepG2 model group， HepG2/ADM model group， sorafenib group （positive drug control group， <italic>ig</italic> 30 mg·kg^-1）， HepG2/ADM+PAE₂ （<italic>iv</italic>） low， medium and high dose groups （50， 100， 200 mg·kg^-1）， HepG2/ADM+PAE₂ （<italic>ig</italic>） low， medium， and high dose groups （50， 100， 200 mg·kg^-1）， skim cream group （<italic>ig</italic> 200 mg·kg^-1）， and CⅡ-3 group （<italic>ig</italic> 200 mg·kg^-1）， all of which received corresponding drug treatment. The body weight and tumor volume of nude mice were measured and recorded every 2 days. The next day after the last administration， tumor tissues of nude mice were taken to record the tumor weight. The effect of <italic>P. americana </italic>polypeptide PAE₂ on permeability-glycoprotein（P-gp）， lung resistance protein（LRP） ， breast cancer resistance protein（BCRP）， protein kinase C（PKC）， glutathione S-transferase-π（GST-π）， topo-isomerase typeⅡ（ToPoⅡ）， multidurg resistance gene 1（MDR1）and Multidrug resistance-associated proteins（MRP1） of the protein level and gene level expression in tumor tissues were determined by immunohistochemistry （IHC） and real-time quantitative polymerase chain reaction （Real-time PCR）. In addition， both oral and intravenous administration groups were set up at the same time for preliminary study on the basic pharmacokinetic characteristics of <italic>P. americana </italic>polypeptide PAE₂. Result:After the successful modeling， the body weight of the nude mice was significantly lower than that in the normal mice（<italic>P</italic><0.05）. After treatment with corresponding drugs， the body weight increased to a certain extent， but it was still not as good as the normal nude mice. In <italic>iv</italic> administration， the medium-dose <italic>P. americana </italic>polypeptide PAE₂ showed the best anti-tumor effect as compared with the model group （<italic>P</italic><0.05）， while in oral administration， the anti-effect increased with the increase of the dose， so the high-dose group showed the best effect （<italic>P</italic><0.05）. Preliminary crude extract CII-3 had no obvious anti-tumor effect， and skim cream showed a certain anti-tumor effect （<italic>P</italic><0.05）. <italic>P. americana </italic>polypeptide PAE₂ had certain effects on MDR related proteins and enzymes<italic> in vivo</italic>， mainly by inhibiting the expression of LRP and BCRP in tumor tissues and affecting the expression of these related proteins and genes to different degrees to inhibit intracellular drugs outflow， thereby promoting tumor apoptosis， and the effect was superior to that of the <italic>P. americana</italic> crude extract CⅡ-3 and skim cream. Conclusion:<italic>P. americana</italic> polypeptide PAE₂ may reduce the drug efflux， promote intracellular drug accumulation and apoptosis by affecting the expression of related proteins and enzymes that mediate multidrug resistance， thereby exerting a reverse effect on HepG2/ADM cells Balb/c MDR in nude mice.

Calycosin down-regulates c-Met to suppress development of glioblastomas

The current case–control study sought the association of BDNF rs6265 and MC4R rs17782313 with metabolic syndrome(MetS), MetS components and other related metabolic parameters in a sample of Pakistani subjects. Fasting high-densitylipoprotein cholesterol (HDL-C) and homeostatic model assessment of insulin sensitivity showed a significantly lowermean whereas body mass index (BMI), waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP),fasting blood glucose, insulin, total cholesterol (TC), low-density lipoprotein cholesterol, very-low-density lipoproteincholesterol, triglycerides (TG), cholesterol to HDL-C ratio, TG to HDL-C ratio, homeostatic model assessment of insulinresistance, visceral adiposity index, lipid accumulation product and the product of TG and glucose showed a significantlyhigher mean in the presence of MetS. Reduced HDL-C appeared as the most frequent and hypertriglyceridemia as the leastfrequent component of MetS whereas clustering of reduced HDL-C ? abdominal obesity (AO) ? hyperglycemia appearedas the most prevalent combination of MetS components. Moreover, BDNF rs6265 showed BMI and gender independentassociation with increased risk of MetS in Pakistani individuals whereas MC4R rs17782313 showed BMI and genderdependent association with increased risk of MetS in Pakistani females. In addition, BDNF rs6265 and MC4R rs17782313showed gender-dependent associations with decreased risk of having low HDL-C in males and increased risk of havingabdominal obesity in females, respectively. However, no association was observed for metabolic variables other thancomponents of MetS across genotypes of both BDNF rs6265 and MC4R rs17782313.

Research Progress of Laportea bulbifera / 中国实验方剂学杂志

The research literature of Laportea bulbifera was summarized and analyzed, and its distribution of literature, chemical composition, pharmacological activity, quality control, clinical application and patent approval were summarized, this study can provide reference for the follow-up clinical application and development and utilization of the herb. Taking CNKI and PubMed database as the retrieval platform, keywords and full text as the search items, the Honghema, Honghuoma, Zhuya Aima, Laportea bulbifera (Siebold & Zuccarini) Weddell. and Laportea bulbifera as the search terms, the domestic and foreign paper reports and patent approvals of L. bulbifera from 1989 to 2018 were retrieved. A total of 41 papers and 63 patents were reviewed, the contents of these papers were pharmacological activity, chemical composition and quality control research, the majority of patents were compound. At present, 73 chemical constituents have been isolated and identified from L. bulbifera, and most of them were flavonoids. Flavonoids, catechins and coumarins were selected as the quality control indexes, and most of the pharmacological activities were anti-inflammatory, analgesic and anti-rheumatism. L. bulbifera is highly competitive in the market because of its remarkable pharmacological activities, however, its quality control level in local standard is low and testing items are incomplete. The determination reported in the literature lacks specific indexes to evaluate the quality of L. bulbifera, at the same time, it is necessary to further study its anti-inflammatory mechanism, explore its quality markers and establish the spectrum-effect relationship, so as to effectively control the quality of L. bulbifera and provide documentation for its comprehensive utilization and resource development.

An association study of single nucleotide polymorphisms of the FOXP3 intron-1 and the risk of Psoriasis vulgaris.

Psoriasis vulgaris (PV) is a common autoimmune disease that involves the dysfunction of CD4+CD25+ regulatory T cells. FOXP3 is a key transcription factor in the development and function of CD4+CD25+ regulatory T cells. Previous studies have demonstrated a genetic association between the FOXP3 gene and some autoimmune diseases. To elucidate the association between the FOXP3 gene and the risk of PV, 408 patients diagnosed with PV and 363 age and sex-matched healthy controls from a cohort of the Chinese majority Han population were recruited. Four single nucleotide polymorphisms (rs2232365, rs3761547, rs3761548 and rs3761549) of the FOXP3 gene were analyzed using the polymerase chain reaction and ligase detection reaction. The major allele of three single nucleotide polymorphisms (SNPs — rs2232365 A, rs3761547 A and rs3761549 C) were associated with an increased risk of PV in a clinical subgroup of female patients, who were less than 40 yrs of age, had a family history of the disease and did not have disease complications (p < 0.05 for all parameters). The haplotype was structured between rs3761547 and rs3761549. An increased risk of PV was observed in haplotype A/A-T/T (p = 0.0055; adjusted OR = 3.188; 95% CI = 0.4354-23.34) and A/G-C/C (p = 0.0082; adjusted OR = 1.288; 95% CI = 0.1529-10.85) between rs3761547 and rs3761549. A synergistic effect was found among the three SNPs. Subjects with the rs2232365AA- rs3761547 AG + GG genotype were more susceptible to PV (p = 0.0393; OR = 2.90; 95% CI = 1.05-7.97). No correlation was found between rs3761548 and the onset of PV. Therefore, the FOXP3 polymorphisms appear to contribute to the risk of psoriasis among the Chinese majority Han population. These findings may aid in our understanding of the pathogenesis of psoriasis