Genome‐wide scans to detect positive selection in Large White and Tongcheng pigs

Due to the direction, intensity, duration and consistency of genetic selection, especially recent artificial selection, the production performance of domestic pigs has been greatly changed. Therefore, we reasoned that there must be footprints or selection signatures that had been left during domestication. In this study, with porcine 60K BeadChip genotyping data from both commercial Large White and local Chinese Tongcheng pigs, we calculated the extended haplotype homozygosity values of the two breeds using the long‐range haplotype method to detect selection signatures. We found 34 candidate regions, including 61 known genes, from Large White pigs and 25 regions comprising 57 known genes from Tongcheng pigs. Many selection signatures were found on SSC1, SSC4, SSC7 and SSC14 regions in both populations. According to quantitative trait loci and network pathway analyses, most of the regions and genes were linked to growth, reproduction and immune responses. In addition, the average genetic differentiation coefficient F_ST was 0.254, which means that there had already been a significant differentiation between the breeds. The findings from this study can contribute to further research on molecular mechanisms of pig evolution and domestication and also provide valuable references for improvement of their breeding and cultivation.     

Isolation and Characterization of Anti-Inflammatory Sorbicillinoids from the Mangrove-Derived Fungus Penicillium sp. DM815

Marine derived fungus has gained increasing ground in the discovery of novel lead compounds with potent biological activities including anti-inflammation. Here, we first report the characterization of one new sorbicillinoid ( 1 ) and fourteen known compounds ( 2 – 15 ) from the ethyl acetate (AcOEt) extract of a cultured mangrove derived fungus Penicillium sp. DM815 by UV, IR, HR ESI-Q-TOF MS, and NMR spectra. We then evaluated the anti-inflammatory effects of eleven sorbicillinoids ( 1 – 11 ) using cultured macrophage RAW264.7 cells. The results show that compound 9 , and to a lesser degree compound 5 , significantly inhibited the Gram-negative bacteria lipopolysaccharide (LPS)-induced upregulation of the inducible nitric oxide synthase (iNOS). Consistently, compounds 5 and 9 significantly reduced the level of nitric oxide (NO), the product of iNOS, induced by LPS. We further show that these two compounds dose-dependently inhibited LPS-triggered iNOS expression and NO production, but had no effect on proliferation of RAW264.7 cells in the presence of LPS. In conclusion, our study identifies novel and known sorbicillinoids as potent anti-inflammatory agents, holding the promise of developing novel anti-inflammation treatment in the future.     

Prostatic Alpha-Linolenic Acid (ALA) Is Positively Associated with Aggressive Prostate Cancer: A Relationship Which May Depend on Genetic Variation in ALA Metabolism

Previous observational studies have reported associations between prostate cancer and alpha-linolenic acid (ALA). However, few investigations have been able to study this relationship prospectively and in well-controlled settings. Moreover, no studies have determined whether single nucleotide polymorphisms (SNPs) that influence ALA metabolism are associated with this common cancer. The purpose of this study was to explore associations between prostatic levels of ALA, SNPs and prostate cancer-specific biomarkers in samples collected from a previous randomized clinical trial conducted using a presurgical model and which tested the effects of flaxseed supplementation, a rich source of ALA, prior to prostatectomy (n = 134). Serum prostate-specific antigen (PSA) was determined and immunohistochemistry was used to assess tumor proliferation rate (Ki67). Prostatic ALA was determined with gas chromatography. Seven previously identified SNPs associated with delta-6 desaturase activity (rs99780, rs174537, rs174545, rs174572, rs498793, rs3834458 and rs968567) were tested for associations with prostatic ALA, PSA and Ki67. Despite consuming seven times more ALA per day, men in the flaxseed arm had similar amounts of prostatic ALA relative to men not consuming flaxseed. In unadjusted analysis, there were significant positive associations between prostatic ALA and PSA (ρ = 0.191, p = 0.028) and Ki67 (ρ = 0.186, p = 0.037). After adjusting for covariates (flaxseed, age, race, BMI and statin-use) the association between ALA and PSA remained (p = 0.004) but was slightly attenuated for Ki67 (p = 0.051). We did not observe associations between any of the SNPs studied and prostatic ALA; however, in models for PSA there was a significant interaction between rs498793 and ALA and for Ki67 there were significant interactions with ALA and rs99780 and rs174545. Independent and inverse associations were observed between rs174572 and Ki67. This study provides evidence that prostatic ALA, independent of the amount of ALA consumed, is positively associated with biomarkers of aggressive prostate cancer and that genetic variation may modify this relationship.     

Autophagy induction by xanthoangelol exhibits anti‐metastatic activities in hepatocellular carcinoma

Xanthoangelol (XAG), a prenylated chalcone isolated from the Japanese herb Angelica keiskei Koidzumi, has been reported to exhibit antineoplastic properties. However, the specific anti‐tumor activity of XAG in human hepatocellular carcinoma (HCC), and the relevant mechanisms are not known. Herein, we evaluated the effect of XAG against HCC in vitro and in vivo. Although XAG treatment did not significantly reduce the viability of the Hep3B and Huh7 cell lines, it suppressed cell migration, invasion, and EMT. This anti‐metastatic effect of XAG was due to induction of autophagy, because treatment with the autophagy inhibitor 3‐methyadenine (3‐MA) or knockdown of the pro‐autophagy Beclin‐1 effectively abrogated the XAG‐induced suppression of metastasis. Mechanistically, XAG induced autophagy via activation of the AMPK/mTOR signaling pathway, and XAG treatment dramatically increased the expression of p‐AMPK while decreasing p‐mTOR expression. In addition, blocking AMPK/mTOR axis with compound C abrogated the autophagy‐mediated inhibition of metastasis. The murine model of HCC metastasis also showed that XAG effectively reduced the number of metastatic pulmonary nodules. Taken together, our results revealed that autophagy via the activation of AMPK/mTOR pathway is essential for the anti‐metastatic effect of XAG against HCC. These findings not only contribute to our understanding of the anti‐tumor activity of XAG but also provide a basis for its clinical application in HCC. Before this study, evidence of XAG on HCC was purely anecdotal; present study provides the first comprehensive assessments of XAG on HCC metastasis and investigates its underlying mechanism. Results suggest that XAG exerts anti‐metastatic properties against HCC through inducing autophagy which is mediated by the activation of AMPK/mTOR signaling pathway. This research extends our knowledge about the antineoplastic properties of XAG and suggests that induction autophagy may represent future treatment strategies for metastatic HCC.     

胆囊结石患者结石形态学特征及血浆脂多糖水平与急性胆源性胰腺炎的关系研究

摘要 目的：探讨胆囊结石患者结石形态学特征及血浆脂多糖（LPS）水平与急性胆源性胰腺炎（ABP）的关系。方法：选取2015年10月~2018年9月期间武汉大学人民医院收治的胆囊结石患者164例为研究对象,分析结石形态学特征与并发ABP的关系,同时采用Logistic回归分析ABP发生的危险因素。将所有患者根据LPS水平分为低LPS组（n=65,<10 pg/mL）以及高LPS组（n=99,≥10 pg/mL）,分析血浆LPS水平对不同结石大小、不同总胆固醇（TG）水平患者并发ABP的影响。结果：多发胆囊结石、球状结石、<3 mm结石、软碎型结石患者并发ABP的概率明显高于单发胆囊结石、不规则状结石或泥沙状结石、3~10 mm结石或>10 mm结石、硬型结石或胶冻型结石（P<0.05）。Logistic回归分析结果显示,多发胆囊结石、球状结石、<3 mm结石以及软碎型结石均是ABP发生的高危因素（P<0.05）。当患者处于高TG水平时,高LPS组并发ABP的概率高于低LPS组（P<0.05）,在细小结石患者中,高LPS组并发ABP的概率高于低LPS组（P<0.05）。结论：依据结石形态学特征可对胆囊结石患者并发ABP的可能性作出早期的判断,同时血浆LPS水平升高是高TG以及细小胆囊结石患者易并发ABP的重要因素之一。     

早期非小细胞肺癌患者血清巨噬细胞抑制因子-1、趋化素与临床病理特征及预后的关系

目的:探讨早期非小细胞肺癌(NSCLC)患者血清巨噬细胞抑制因子-1(MIC-1)、趋化素(chemerin)水平与临床病理特征及预后的关系。方法:选择72例NSCLC患者(NSCLC组)、53例肺良性疾病患者(良性组)、50例体检健康人群(对照组),分别检测血清MIC-1、chemerin水平,分析血清MIC-1、chemerin水平与NSCLC患者临床病理参数的关系。Kaplan-Meier法分析不同血清MIC-1、chemerin水平NSCLC患者生存时间的差异,COX比例风险回归分析血清MIC-1、chemerin水平与NSCLC患者预后的关系。结果:NSCLC组患者血清MIC-1、chemerin水平高于良性组和对照组(P0.05)。血清MIC-1水平与NSCLC患者年龄、目前吸烟、肿瘤直径、TNM分期、分化程度、复发或转移、生存状态有关(P0.05),chemerin水平与NSCLC患者目前吸烟、TNM分期、复发或转移、生存状态有关(P0.05)。高MIC-1水平患者生存率低于低MIC-1水平患者(P0.05),高chemerin水平患者生存率低于低chemerin水平患者(P0.05)。COX比例风险回归分析结果显示:血清MIC-1、chemerin、TNM分期与NSCLC不良预后独立相关。结论:血清MIC-1、chemerin水平与NSCLC患者部分临床病理参数和预后相关,可作为早期NSCLC患者预后预测的潜在指标。