The clinicopathological and gene expression patterns associated with ulceration of primary melanoma

Ulceration of primary melanomas is associated with poor prognosis yet is reported to predict benefit from adjuvant interferon. To better understand the biological processes involved, clinicopathological factors associated with ulceration were determined in 1804 patients. From this cohort, 348 primary tumor blocks were sampled to generate gene expression data using a 502‐gene cancer panel and 195 blocks were used for immunohistochemistry to detect macrophage infiltration and vessel density. Gene expression results were validated using a whole genome array in two independent sample sets. Ulceration of primary melanomas was associated with more proliferative tumors, tumor vessel invasion, and increased microvessel density. Infiltration of tumors with greater number of macrophages and gene expression pathways associated with wound healing and up‐regulation of pro‐inflammatory cytokines suggests that ulceration is associated with tumor‐related inflammation. The relative benefit from interferon reported in patients with ulcerated tumors may reflect modification of signaling pathways involved in inflammation.     

刺参“腐皮综合症”致病菌LNUB415的分离及防治的初步研究

从大连海域患“腐皮综合症”的养殖刺参肠道中分离纯化到1株优势细菌LNUB415,经人工回接感染试验确定其对刺参具有较强的致病性.经形态学、生理生化和16S rDNA序列分析,该菌被初步鉴定为蜡样芽胞杆菌(Bacillus cereus).从多种具有免疫增强作用的中草药中筛选到抑菌效果最好的黄连,可使刺参死亡率降低30％.     

幽门螺杆菌感染对延缓乙酸诱导大鼠胃溃疡愈合的实验研究

本工作旨在观察幽门螺秆菌（Ｈｅｌｉｃｏｂａｃｔｅｒｐｙｌｏｒｉ,ＨＰ）感染对大鼠乙酸性胃溃疡愈合的影响。实验发现,大鼠发生乙酸性溃疡后,一次性接种ＨＰ几乎使所有大鼠感染,并引起胃溃疡的自然愈合明显减慢;组织学和生化检测观察到ＨＰ组大鼠胃溃疡病灶处有更多炎症细胞浸润,以中性粒细胞为主,未受溃疡累及的胃窦和胃后壁粘膜也有炎症细胞浸润;免疫组化研究发现ＨＰ组胃粘膜出现较多的ＩＬ－８阳性细胞;此外发现ＨＰ组胃粘膜ＢｒｄＵ标记细胞显著减少,既粘膜上皮的再生减慢。结果提示,ＨＰ感染延缓乙酸性溃疡的愈合,后者与ＨＰ感染后增加ＩＬ－８表达所诱导更强的炎症反应和粘膜细胞再生减慢有关。     

Application of proteomics to the study of Helicobacter pylori and implications for the clinic

Introduction: Helicobacter pylori (H. pylori) is a gram-negative bacterium that colonizes the gastric epithelium and mucous layer of more than half the world’s population. H. pylori is a primary human pathogen, responsible for the development of chronic gastritis, peptic ulceration and gastric cancer. Proteomics is impacting several aspects of medical research: understanding the molecular basis of infection and disease manifestation, identification of therapeutic targets and discovery of clinically relevant biomarkers.

Areas covered: The main aim of the present review is to provide a comprehensive overview of the contribution of proteomics to the study of H. pylori infection pathophysiology. In particular, we focused on the role of the bacterium and its most important virulence factor, CagA, in the progression of gastric cells transformation and cancer progression. We also discussed the proteomic approaches aimed at the investigation of the host response to bacterial infection.

Expert commentary: In the field of proteomics of H. pylori, comprehensive analysis of clinically relevant proteins (functional proteomics) rather than entire proteomes will result in important medical outcomes. Finally, we provided an outlook on the potential development of proteomics in H. pylori research.     

仿刺参“化皮病”体壁组织DNA甲基化的MSAP分析

利用甲基化敏感扩增多态性(Methylation-sensitive amplified polymorphism, MSAP)技术分析了健康仿刺参(Apostichopus japonicus)体壁和“化皮病”仿刺参病变体壁、正常体壁DNA序列中CCGG位点的甲基化情况。结果显示, 健康仿刺参体壁和“化皮病”仿刺参病变体壁、正常体壁总甲基化水平分别为(18.60±5.61)%、(26.70±6.82)%和(19.53±3.34)%, 其中全甲基化水平分别为(13.97±4.86)%、(20.08±5.26)%和(15.42±2.61)%, 半甲基化水平分别为(4.63±3.59)%、(6.62±3.80)%和(4.11±2.08)%。“化皮病”仿刺参病变体壁总甲基化水平和全甲基化水平显著高于健康仿刺参体壁和“化皮病”仿刺参正常体壁(P<0.05), 健康仿刺参体壁与“化皮病”仿刺参正常体壁总甲基化水平和全甲基化水平差异不显著(P>0.05); 三者的半甲基化水平无显著差异(P>0.05)。因此, 推测仿刺参体壁“化皮”与DNA甲基化有关。     

Evidence and impact of neutrophil extracellular traps in malignant melanoma

Ulceration of melanoma is associated with neutrophil infiltrates and lower survival rates opposite to non‐ulcerated melanoma. Neutrophils release neutrophil extracellular traps (NETs) that are chromatin structures loaded with antimicrobial proteins. Since NETs have been correlated with tumor progression, we investigated whether NETs appear in melanoma and affect melanoma cells. Indeed, human primary melanoma biopsies revealed neutrophils releasing NETs in all of 27 ulcerated melanomas, whereas NETs were absent in all of 7 non‐ulcerated melanomas. However, the quantity of intratumoral NETs did not correlate with tumor progression of melanoma. Interestingly, in vitro assays showed that melanoma cells attach to NETs via integrin‐mediated adhesion and that NETs inhibit tumor cell migration. Moreover, co‐culturing of NETs and melanoma cells had a cytotoxic effect on melanoma cells resulting in necrosis. Hence, we discovered in vitro an antineoplastic role of NETs in melanoma.     

New nitric oxide donating 1,2,4-triazole/oxime hybrids: Synthesis,investigation of anti-inflammatory,ulceroginic liability and antiproliferative activities

A series of novel nitric oxide (NO) donating triazole/oxime hybrids was prepared and evaluated for their anti-inflammatory activity. Most of the tested compounds showed significant anti-inflammatory activity using carrageenan-induced rat paw edema method compared to indomethacin. Calculation of the ulcer indices and histopathological investigation indicated that the prepared NO-donating oximes exhibited less ulcerogenicity compared to their intermediate ketones and indomethacin. The NO-donating oxime 6i revealed significant activity against renal cancer A498 cell lines with 50.52 cell growth inhibition.     

Anti‐inflammatory effects of eriocitrin against the dextran sulfate sodium–induced experimental colitis in murine model

Inflammatory bowel disease (IBD) is a continual ailment condition which engrosses the entire alimentary canal. The IBD can be primarily distinguished into two forms, ulcerative colitis, and Crohn's disease. The major symptoms of IBD include pustules or abscesses, severe abdominal pain, diarrhea, fistula, and stenosis, which may directly affect the patient's quality of life. A variety of mediators can stimulate the circumstances of IBD, some examples include infections by microbes such as bacteria, perturbation of the immune system and the surrounding environment of the intestines. Severe colitis was stimulated in the experimental animals through administering 4% dextran sulfate sodium (DSS) which is mixed in water ad libitum for 6 days. Eriocitrin (30 mg/kg) was then administered to the experimental animals followed by the induction of severe colitis to evaluate the therapeutic prospective of eriocitrin against the colon inflammation stimulated by DSS. In this study, eriocitrin (30 mg/kg) demonstrated significant (P < .05) attenuation activity against the DSS‐stimulated severe colitis in experimental animals. Eriocitrin counteracted all of the clinical deleterious effects induced by DSS, such as body‐weight loss, colon shortening, histopathological injury, accretion of infiltrated inflammatory cells at the inflamed region and the secretion of inflammatory cytokines. The results clearly showed that eriocitrin effectively attenuated DSS‐induced acute colitis in experimental animals.     

脑室注射5-HT对应激后胃粘膜中ATP酶活性及ATP和ADP含量的影响

中枢5-羟色胺(5-HT)可通过兴奋下丘脑-垂体-甲状腺轴加重大鼠冷冻加束缚应激性溃疡。本工作进一步观察了脑室注射5-HT对胃粘膜代谢的影响及其与甲状腺激素的关系。应激180min大鼠的胃粘膜ATP酶的活性较非应激发对照鼠升高42.6％;如应激前10min向侧脑室注射5-HT50μg或腹腔注射四碘甲腺原氨酸(T_4)200μg/kg,均匀进一步提高应激后胃粘膜ATP酶的活性。在侧脑室注射5-HT后应激180min的鼠,血浆三碘甲腺原氨酸(T_3)和T_4水平均与胃粘膜ATP酶的活性呈明显的正相关关系。用高效液相层析测定观察到,应激鼠胃粘膜ATP和ADP水平均明显低于非应激鼠,分别为非应激鼠的70.3％和76.8％。腹腔注射T_4进一步减少应激后胃粘膜ATP和ADP的水平。这些结果提示,中枢5-HT可能通过甲状腺激素提高胃粘膜ATP酶的活性,使ATP和ADP含量下降,这可能与其加重溃疡的机制有关。