KLK8 promotes the proliferation and metastasis of colorectal cancer via the activation of EMT associated with PAR1

Kallikrein-related peptidase 8 (KLK8) acts as an oncogene or anti-oncogene in various tumours, and the abnormal expression of KLK8 is involved in the carcinogenesis of several tumours. However, the role of KLK8 in colorectal cancer (CRC) and the underlying mechanism remain largely unclear. In this study, the carcinogenic effect of KLK8 was determined via CCK-8 and colony formation assays in vitro and a xenograft model in nude mice in vivo. The metastasis-promoting effect of KLK8 was investigated with transwell migration and invasion assays and wound-healing assay in vitro and a metastasis model in nude mice in vivo. Bioinformatics analyses and mechanistic experiments were conducted to elucidate the molecular mechanism. Herein, we reported that KLK8 had a promotive effect on the proliferation, migration and invasion of RKO and SW480 cells. Epithelial−mesenchymal transition (EMT) played an important role in the promotive effects of KLK8 on CRC. In addition, protease-activated receptor-1 (PAR-1) antagonist {"type":"entrez-protein","attrs":{"text":"SCH79797","term_id":"1052762130","term_text":"SCH79797"}}SCH79797 but not protease-activated receptor-2 (PAR-2) antagonist FSLLRY-NH2 attenuated the proliferation, migration and invasion of KLK8-upregulated RKO and SW480 cells. PAR-1 antagonist {"type":"entrez-protein","attrs":{"text":"SCH79797","term_id":"1052762130","term_text":"SCH79797"}}SCH79797 reduced the tumour volume of xenograft model and decreased the metastatic nodules in the livers of metastasis model. Furthermore, {"type":"entrez-protein","attrs":{"text":"SCH79797","term_id":"1052762130","term_text":"SCH79797"}}SCH79797 could reverse the positive impact of KLK8 on the EMT process in CRC both in vitro and in vivo. Taken together, these findings demonstrated for the first time that KLK8 promoted EMT and CRC progression, and this effect might be, at least partly mediated by PAR1-dependent pathway.Subject terms: Colorectal cancer, Oncogenes, Tumour biomarkers     

Opposing impact of AID deficiency on BCL-2 and IL-6 driven B-lymphoma development in BALB/c mice

Activation-induced cytidine deaminase (AID), an essential enzymatic activity required for somatic hypermutation and immunoglobulin class switch recombination in the course of normal B-lymphocyte development, has been implicated in the initiation and promotion of malignant B-cell tumors by virtue of a complex mechanism that includes the generation of oncogene-activating genomic rearrangements and the introduction of point mutations in cancer genes. Here, we use transgenic mouse models of B-cell lymphoma driven by the pro-inflammatory cytokine, interleukin 6 (IL-6), or the survival-enhancing oncoprotein, B-cell leukemia 2 (BCL-2), to evaluate the impact of loss of AID on neoplastic B-cell development. We show that AID deficiency accelerates BCL-2 induced lymphoma but delays IL-6 induced lymphoma. This led us to conclude that AID may function as tumor suppressor or tumor promoter, depending on the genetic context. Elucidating the mechanism of AID''s dual function during malignant B-cell transformation may be important for new approaches to tumor treatment and prevention.     

关于蔬菜腌渍发酵亚硝酸盐问题的探讨

综述多篇文献,探讨分析认为:蔬菜自然发酵过程中“亚硝峰”出现的时间应在环境pH 4.0左右;“亚硝峰”前应有亚硝酸盐大量被酶降解;对各因素影响蔬菜腌渍发酵亚硝酸盐消长的原因进行分析。在此基础上构想了理想的蔬菜腌渍发酵工艺。     

柑橘黄龙病株不同部位内生细菌群落结构的多样性

采用PCC(Pearson correlation coefficient)、系统聚类和多样性指数研究了柑橘黄龙病(citrus huanglongbing,HLB)植株不同部位叶片、枝条及其根部内生细菌的相互关系及其群落结构多样性.结果表明,从供试柑橘中分离得到26株内生细菌(叶片10株,枝条14株,根部2株)隶属于10个属19个种.Nested-PCR结果显示,柑橘植株不同空间叶片中,黄龙病病原的阳性检出率为58.3％.用LSD法比较显示,柑橘内生细菌在不同器官的分布量大小依次为根＞叶＞枝条.上、中、下不同部位叶片和枝条内生细菌分布量差异不显著,而东、西、南、北不同方位的叶片和枝条内生细菌分布量差异显著(P＜5％).柑橘内生细菌之间的PCC分析表明,Bacillus pumilus和Bacillus sp.与柑橘黄龙病病原菌呈显著负相关,Bacillus sp.和Bacillus pumilus与Bacillus subtilis呈显著正相关.Bacillus brevis和Escherichia hermannii与Bacillus vesiculariss存在显著正相关.对柑橘不同器官内生细菌的PCC分析表明,同种器官的内生细菌之间呈正相关,不同器官的内生细菌之间呈负相关.以内生细菌在各器官的分布量为指标分析不同器官之间的相关性,结果表明,叶片与枝条呈正相关,PCC为0.55,叶片与根部、枝条与根部均呈负相关,PCC分别为-0.19和-0.13.16S rDNA序列聚类分析表明,柑橘内生细菌可分为两大类,第Ⅰ大类为革兰氏阳性菌,第Ⅱ大类为革兰氏阴性菌.第Ⅰ大类又可以分为芽孢杆菌属和短小杆菌属两个亚类,第Ⅱ大类也可以分两个亚类.对柑橘黄龙病病原与叶片内生细菌进行聚类分析,可以分为三类,第Ⅰ类特征为内生细菌存在所有部位的叶片;第Ⅱ类特征为内生细菌与黄龙病病原菌存在负相关性;第Ⅲ类特征为内生细菌只存在特定部位叶片.当马氏距离为27.23时,可将柑橘黄龙病内生细菌群落结构聚为3类,第Ⅰ类特点是在不同部位叶片均有分布,为完全分布类型,且分布量较大,第Ⅱ类特点是在各器官中均为不完全分布类型,且分布量不均匀,第Ⅲ类特点是根部分布特性且分布量较大.分析多样性指数表明,SHANNON(H1)指数在叶片最高,根部最低.SIMPSON(D)指数在枝条最高,根部最低.Pielou指数在根部最高,枝条最低.     

氯盐胁迫下氮素对西瓜根系生长的调控作用

为揭示氯盐胁迫下氮素对西瓜根系的调节机制和提供西瓜氯毒害调控理论依据,以西瓜为供试作物,采用土培试验,研究不同施氮量(0,0.1,0.15,0.2,0.25 g/kg)对氯盐胁迫下西瓜根系的影响,并应用主成分分析法对各施氮量下根系生长情况进行综合评价。结果表明,(1)与不施氮相比,施氮0.15 g/kg处理可使西瓜根系生物量、干物质累积量、脯氨酸含量、可溶性糖含量、根系活力分别显著提高58.83%、20.83%、98.33%、70.37%和29.44%,丙二醛含量显著降低40.30%,同时使总根长、总根表面积、根尖数、分枝数分别显著增加103.42%、46.41%、64.44%、87.80%,总根体积和总根系直径分别减少23.05%和40.15%。(2)在本试验氯盐胁迫条件下,施氮0.14~0.17 g/kg时西瓜具有较理想的根系构型和较高的根系活力。(3)根系分枝数、根系活力、总根体积、根尖数可作为氯盐胁迫下氮素对西瓜根系生长影响的综合评价指标,各施氮水平对氯盐胁迫的缓解效果表现为0.15 g/kg>0.20 g/kg>0.10 g/kg>0.25 g/kg。可见,在氯盐胁迫下,适量施氮有助于西瓜建立良好的根系构型,提高根系渗透物质含量,降低细胞渗透势,减少根系丙二醛含量,维持较强的根系活力,增加根系生物量和干物质,缓解高浓度氯盐对西瓜生长的抑制作用。     

Requisite H2k role in NK cell-mediated resistance in acute murine cytomegalovirus-infected MA/My mice

Human CMV infections are a major health risk in patients with dysfunctional or compromised immunity, especially in patients with NK cell deficiencies, as these are frequently associated with high morbidity and mortality. In experimental murine CMV (MCMV) infections, Ly49H activation receptors on C57BL/6 (B6) NK cells engage m157 viral ligands on MCMV-infected cells and initiate dominant virus control. In this study, we report that MCMV resistance in MA/My relies on Ly49H-independent NK cell-mediated control of MCMV infection as NK cells in these mice do not bind anti-Ly49H mAb or soluble m157 viral ligands. We genetically compared MA/My resistance with MCMV susceptibility in genealogically and NK gene complex-Ly49 haplotype-related C57L mice. We found that MCMV resistance strongly associated with polymorphic H2k-linked genes, including MHC and non-MHC locations by analysis of backcross and intercross progeny. The H2b haplotype most frequently, but not absolutely, correlated with MCMV susceptibility, thus confirming a role for non-MHC genes in MCMV control. We also demonstrate a definite role for NK cells in H2k-type MCMV resistance because their removal from C57L.M-H2k mice before MCMV infection diminished immunity. NK gene complex-linked polymorphisms, however, did not significantly influence MCMV control. Taken together, effective NK cell-mediated MCMV control in this genetic system required polymorphic H2k genes without need of Ly49H-m157 interactions.     

乙型肝炎IgM和IgG—补体双特异性循环免疫复合物的意义

对不同临床类型的乙型肝炎患者,采用捕捉法ＥＬＩＳＡ,以ＩｇＭ和ＩｇＧ类抗体排除抗原性异物的免疫反应进行比较研究。结果发现,两种反应能力在慢性ＨＢＣ感染中基本相同,表现出明显的病型差异,而在急性ＨＢＶ感染中则不同,前者反应强度显著主于后者;二者阳性率在慢性ＨＢＶ感染的临床类型中虽均随其肝损害加重而显著上升,但ＩｇＧ／Ｃ３双特异性循环免疫复合物与ＡＬＴ有关,而ＩｇＭ／Ｃ３－ＴＣＩＣ与ＡＬＴ无关;二者阳