红霉素对4-羟基壬烯醛刺激的气道上皮细胞MMP-2、MMP-9、COX-2和 AP-2表达的影响

目的：观察红霉素对4-羟基壬烯醛(4-HNE)刺激的气道上皮细胞基质金属蛋白酶2(MMP-2)、MMP-9、环氧合酶2(COX-2)和活化蛋白-2(AP-2)表达的影响。方法 Western blot 检测红霉素(5μmol/L)预孵育不同时间(24、36、48 h)后4-HNE(10μmol/L 作用4 h)刺激的气道上皮细胞MMP-2、MMP-9、COX-2和 AP-2蛋白表达的变化。结果红霉素预孵育36 h 和48 h 后明显抑制4-HNE刺激的气道上皮细胞 MMP-2、MMP-9、COX-2合成,明显抑制4-HNE 刺激的气道上皮细胞核转录因子 AP-2的激活,与红霉素未预孵育组相比,差异具有统计学意义(P <0.05)。结论红霉素可明显抑制4-HNE 刺激的气道上皮细胞 MMP-2、MMP-9、COX-2表达,其机制可能和抑制核转录因子 AP-2的激活有关。     

The effects of PGF2 alpha, PGI2, and TxB2 on human CFU-C in healthy and leukemic patients

This study was undertaken to test the effects of certain arachidonate derivatives, PGF2 alpha, PGI2 and TxB2 on in vitro bone marrow granulocyte colony growth (CFU-C) in leukemia patients receiving maintenance chemotherapy and in normal controls. The addition of PGF2 alpha did not result in increased numbers of colonies, but it did cause a shift in the size of the colonies so that there was a significant increase in larger colonies (P less than 0.001) and significantly fewer small colonies (P less than 0.05) as compared to untreated samples. Of the prostenoids tested in a Tris-buffered system, PGI2 affected the greatest increase in CFU-C (P less than 0.01) followed by PGF2 alpha (P less than 0.05) whereas 6-keto-PGF1 alpha (the stable hydrate of PGI2) did not affect colony growth. Time-response curves revealed a linear growth pattern for PGF2 alpha with a peak at 10 days, whereas there was a 6-day growth lag with PGI2 followed by linear growth with a peak at 13 days. TxB2 added to cultures significantly reduced the number of bone marrow CFU-C at all doses tested. The prostanoid effects on CFU-C derived from leukemic patients on maintenance chemotherapy and from normal individuals were identical in every respect.     

幽门螺杆菌感染与胃癌及癌前病变中c-myc、p53、C-erbB-2及bcl-2蛋白表达关系的研究

目的 观察胃癌、癌前病变中幽门螺杆菌(Hp)感染情况及其与c-myc、p53、c-erbB-2、bcl-2在胃癌及癌前病变中的表达关系,探讨Hp在胃癌、癌前病变发生及发展中的作用以及探索从癌前病变到癌变过程中的基因变化规律.方法 放大内镜及超声内镜检查收集103例胃黏膜标本,用免疫组织化学染色方法检测Hp感染及不同组织间c-myc、p53、c-erbB-2、bcl-2的表达.结果 c-myc、p53、c-erbB-2和bcl-2阳性表达率在胃癌组及癌前病变组中呈过度表达,与正常对照组相比有显著性差异(P<0.05).此外,Hp感染组c-myc、p53、c-erbB-2及bcl-2同时表达者为5例(9.4%);与无Hp感染组相比有显著性差异(P<0.01).结论 胃癌及癌前病变中组织存在c-myc、p53、c-erbB-2、bel-2多个表达,与Hp感染密切相关.     

胃乐散对大鼠溃疡组织TXA2、PGI2 及COX-2含量的影响及意义

目的 观察胃乐散对大鼠实验性溃疡血栓素A2(TXA2)和前列腺素I2( PGI2)及环氧合酶2(COX-2)的影响,并探讨其作用机理.方法 SD大鼠48只,随机分为正常对照组、模型组、胃乐散低剂量组、胃乐散中剂量组、胃乐散高剂量组和雷尼替丁组.采用冰醋酸烧灼法制备大鼠胃溃疡模型,连续用药后第14天处死大鼠,取溃疡部位组织提取蛋白.用ELISA法检测组织中血栓素B2(TXB2)和6-酮-前列腺素F1α(6-Keto-PGF1α)的水平变化,并观察TXB2/6-Keto-PGF1α的比值变化.Western blot检测组织中COX-2的含量.结果 与正常对照组比较,模型组6-Keto-PGF1α、COX-2水平降低(P＜0.05),TXB2及TXB2/6-Keto-PGF1α升高(P＜0.05);胃乐散高剂量组6-Keto-PGF1α的含量高于正常对照组(P＜0.05).与模型组比较,胃乐散中、高剂量组及雷尼替丁组6-Keto-PGF1α、COX-2的含量增加,特别是胃乐散高剂量组增加更为明显(P＜0.01),胃乐散高剂量组及雷尼替丁组TXB2低于模型组(P＜0.05),特别是TXB2/6-Keto-PGF1α降低更为显著(P＜0.01).结论 胃乐散治疗胃溃疡可能是通过促进PGI2分泌,纠正TXA2/PGI2的失衡来实现的.     

溴氰菊酯和三氯杀虫酯现场灭蛉效果观察

用2.5％可湿性溴氰菊酯和国产三氯杀虫酯(7504)进行现场喷洒灭蛉结果表明,每平方米墙面使用溴氰菊酯37.5mg、25mg和12.5mg剂量,可使白蛉数量比对照区降低13—19倍,削平季节高峰。当年的灭蛉效果超过50％的可湿性DDT。在模拟土墙和泸纸药膜上,残效至少可达50天以上。建议以每平方米12.5mg作为灭蛉喷洒剂量推广使用;7504每平方米1g的剂量可使白蛉数量降低8.9倍,值得进一步试用,但其剂型应研究改进。连续观察证明,在当地条件下,于喷洒后第三年白蛉密度可恢复到具有流行病学意义的程度。     

ACE2与糖尿病及其并发症

血管紧张素转换酶(ACE)2是近年来新发现的一种单羧肽酶,是已知的第一个ACE同系物.ACE2催化血管紧张素(Ang)Ⅱ生成Ang(1-7),后者与Mas受体结合,从而启动对AngⅡ信号级联反应的抑制作用.ACE2能够通过增加胰岛血流灌注、抑制细胞凋亡,促进胰岛素分泌,有效延缓糖尿病患者胰岛素功能衰退的发展.此外,在糖尿病微血管和大血管病变的病理生理过程中,ACE2发挥抗ACE效应,调控心脏、视网膜和肾脏的缩、扩血管的平衡.ACE2及其激活剂、拮抗剂,可能在糖尿病及其并发症的防治领域具有极其广阔的临床应用前景.     

NEK2及ERK2在乳腺癌中的表达及意义

目的通过检测乳腺原位癌及浸润性癌组织中NIMA相关蛋白激酶NEK2和细胞外信号调节激酶ERK2的表达,探讨其在乳腺癌变过程中发挥的作用。方法采用免疫组织化学ElivisionTMplus两步法,研究86例乳腺浸润性癌、10例乳腺原位癌、20例乳腺组织的表达情况。结果 NEK2在3组中的表达情况分别为87.2%、50.0%、10.0%。ERK2在3组中的表达情况分别为96.7%、80.0%、10.0%。NEK2与ERK2的表达呈正相关。NEK2蛋白和ERK2蛋白的表达均与患者发生肿瘤的淋巴结转移、病理学分级及临床分期呈明显正相关,而与患者的年龄,肿物大小,月经情况,组织分型无关。结论 ERK2相关信号传导通路和NEK2共同作用参与了乳腺癌的形成过程。     

Alterations of p53, Bcl-2, and hMSH2 protein expression in the cirrhotic, macroregenerative, dysplastic nodules and hepatocellular carcinomas in Upper Egypt.

BACKGROUND: Hepatocarcinogenesis involves alterations in p53, Bcl-2 and human Mut S homologue-2 (hMSH2) genes. In Upper Egypt, the clinicopathologic and genetic changes during hepatocarcinogensis (cirrhotic nodules (CN); macroregenerative nodules (MRN) and dysplastic nodules (DN) are unknown. METHODS: To examine these issues, 48 hepatic resection specimens entailing 25 CN, 16 MRN, 23 DN and 48 hepatocellular carcinoma (HCC) were immunohistochemically evaluated for p53, Bcl-2 and hMSH2 protein expression. RESULTS: HCC was common in males than in females (2.6:1, P<0.05) and with hepatitis C virus than hepatitis B virus infection (77.1% vs. 18.7%, P=0.001). p53 expression was found in DN (3/23) and HCC (12/48). Its average weighted scores were high in DN/HCC as compared with CN (1.60+/-0.40 and 7.20+/-1.20, P=0.0001). Bcl-2 expression was seen in CN, MRN, DN and HCC (7/48). Its average weighted scores were high in DN (7.60+/-1.60), HCC (6.86+/-0.85) as compared with CN (6.14+/-0.42) and MRN (6.50+/-0.50, P=0.22). hMSH2 average weighted scores were reduced in HCC (7.94+/-1.06) as compared with CN (8.47+/-0.52), MRN (8.00+/-1.00) and DN (8.20+/-0.80, P>0.05). CONCLUSION: In Upper Egypt: (1) HCC had similar clinicopathologic features to those in the high-risk regions, and (2) alterations of the p53, Bcl-2 and hMSH2 proteins occur during hepatocarcinogensis.     

COX-2和MMP-2的表达与食管癌侵袭转移的关系

目的探讨COX－2和MMPZ的表达与食管癌侵袭和转移的关系。方洁应用兔疫组织化学（S法）检测COX．2、 ＊＊kZ在45例食管鳞癌，癌旁组织中的表达。结果＊ox之和＊＊P之在食管癌组织中表达的阳性率显著高于癌旁组织（P＜ 0．05）O COLZ和＊M卜2在有外膜浸润组和淋巳结转移组阳性表达率明显高于无外膜浸润组和无淋巴结转移组（P＜0．0到。C012 和＊＊＊2在食管癌组织中的表达密切相关（P＜0刀别。结论食管癌组织中C0lz和＊M卜2的高表达促进了食管癌的侵袭和转 移，COX．2利MMPZ在食管癌组织中的表达有相关性。提示COX．2和MMP毛可作为判断预后的指标和化学治疗的靶点。     

c-Jun,Fra-2, and ATF-2 Immunoreactivity in the Jejunal Tissues of the Healthy Rat

The aim of this study was to compare the localization of some activator protein-1 (AP-1) proteins in healthy rat jejunum. For this purpose, the AP-1 members c-Jun, Fra-2, and ATF-2 immunoreactivity (c-Jun-IR, Fra-2-IR, ATF-2-IR) in villus epithelial cells (ECs), intravillous lamina propria cells (LPCs), crypt cells (CCs), and smooth muscle cells (SMCs) were analyzed by immunohistochemical methods. Among all the cell groups, the lowest positivity ratio was found in c-Jun-IR and the highest positivity ratio was found in ATF-2-IR. For each group of ECs, LPCs, CCs, and SMCs, c-Jun-IR, Fra-2-IR, and ATF-2-IR were compared and statistically significant differences found. There were no significant differences among the cell groups with respect to c-Jun-IR and Fra-2-IR, but there was a statistically significant difference in ATF-2-IR. These findings suggest that each member of AP-1 is expressed differently and that ATF-2 is more active than c-Jun and Fra-2 in physiological conditions in healthy rat jejunum.     

白细胞介素—2及其受体与乙型肝炎疫苗接种无、弱应答发生的关系

OBJECTIVE: To study the relationship between interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R) and the non-and-hypo-responsiveness to hepatitis B vaccine. METHODS: Peripheral blood mononuclear cells (PBMC) isolated from 21 non-and -hypo-responders, 22 hyperresponders and 21 chronic HBsAg carriers were incubated in the presence of HBsAg and phytohaemagglutinin (PHA). The levels of IL-2 and sIL-2R in the supernatants of activated cells were measured by an enzyme-linked immunosorbent assay. RESULTS: The average level of IL-2 in the non-and-hypo-responders was significantly lower than that in the hyperresponders (t=8.80, P<0.001), but was comparable to that in chronic HBsAg carriers (q=0.06, P>0.5). Between the hyperresponders and the non-and-hypo-responders, the average sIL-2R levels showed no noticeable difference. CONCLUSION: The results suggest that low level of IL-2 may be one of the causes and mechanisms of non-and-hypo-responsiveness to hepatitis B vaccine.     

Renal safety of canagliflozin,a sodium glucose co‐transporter 2 inhibitor,in patients with type 2 diabetes mellitus

The incidence of renal‐related adverse events (AEs) with canagliflozin in patients with type 2 diabetes mellitus from a pooled population of patients in 7 active‐ and placebo‐controlled trials (N = 5598) and in a 104‐week study vs glimepiride (N = 1450) was low and similar in canagliflozin and non‐canagliflozin groups. In the study vs glimepiride, canagliflozin was associated with an initial acute decrease in estimated glomerular filtration rate (eGFR) that attenuated over time, while eGFR declined progressively over 104 weeks with glimepiride. The incidence of renal‐related AEs with canagliflozin was generally stable over time, while the incidence with glimepiride increased over 104 weeks. In the present analysis, based on postmarketing reports from the US Food and Drug Administration Adverse Event Reporting System, a potential signal was identified for acute kidney injury with all approved sodium glucose co‐transporter 2 (SGLT2) inhibitors (ie, canagliflozin, dapagliflozin and empagliflozin). The early onset of acute kidney injury events with SGLT2 inhibitors in postmarketing reports probably reflects the acute changes in eGFR attibutable to the known renal haemodynamic effects of SGLT2 inhibition.     

The H2O2-Generating Enzyme,Xanthine Oxidase,Decreases Luminal Ca2+ Content of the IP3-Sensitive Ca2+ Store in Vascular Endothelial Cells

Objective: Xanthine oxidase inhibits agonist-stimulated Ca²⁺ signaling in calf pulmonary artery endothelial cells by an H₂O₂-dependent mechanism. We investigated the effect of xanthine oxidase on luminal Ca²⁺ content of the inositol-1,4,5-trisphosphate (IP₃)-sensitive Ca²⁺ store. Methods: Luminal Ca²⁺ content was estimated from the net release of Ca²⁺ activated by 2,5-di-t-butylhydroquinone (BHQ), an inhibitor of microsomal Ca²⁺ pumps. Results: Initially, xanthine oxidase depleted the IP₃-sensitive Ca²⁺ store of releasable Ca²⁺, but with more prolonged incubation, the enzyme also depleted non-IP₃-sensitive stores. In addition, xanthine oxidase inhibited capacitative Ca²⁺ influx. Similar results were observed when thapsigargin was substituted for BHQ. Conclusions: Depletion of luminal Ca²⁺ content within the IP₃-sensitive Ca²⁺ store contributes to xanthine oxidase inhibition of Ca²⁺ signaling in vascular endothelial cells.     

4-羟基壬烯醛上调气道上皮细胞MMP-2、MMP-9和COX-2的表达

目的 观察4-羟基壬烯醛(4-HNE)对气道上皮细胞基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)和环氧合酶2(COX-2)表达的影响.方法 Western-blot和RT-PCR检测不同浓度4-HNE(0μmol/L,10 μmol/L,30 μmol/L和50 μmol/L)作用气道上皮细胞4h后MMP-2、MMP-9和COX-2蛋白和mRNA表达的变化.结果 4-HNE以剂量依赖的方式促进MMP-2、MMP-9、COX-2mRNA表达和蛋白合成,与对照组相比,差异具有统计学意义(P＜0.05).结论 4-HNE可通过上调气道上皮细胞COX-2的表达而导致慢性阻塞性肺疾病患者慢性气道炎症的发生、发展,上调MMP-2、MMP-9的表达引起慢性阻塞性肺疾病患者的气道重塑.     

Interaction between cyclooxygenase-2,Snail,and E-cadherin in gastric cancer cells

AIM:To investigate the mechanisms of how cyclooxygenase-2(COX-2)regulates E-cadherin in gastric cancer cells.METHODS:COX-2 expression in human gastric cancer cell lines SGC-7901,BGC-823,MGC-803 and AGS were measured at the mRNA and protein level.COX-2 rich cell line SGC-7901 was chosen for subsequent experiments.siRNA mediated gene knockdown was used to investigate the impact of COX-2 on nuclear factor-κB (NF-κB),Snail,and E-cadherin in gastric cancer cells.Gene expression was determined by Western blot and real-time polymerase chain reaction.To analyze whether NF-κB inhibition could interrupt the modulatory effect of COX-2 or prostaglandin E2(PGE2)on E-cadherin,gastric cancer cells were treated with celecoxib or PGE2,in the presence of NF-κB specific siRNA.RESULTS:Highest expression level of COX-2 was found in SGC-7901 cells,both at mRNA and protein levels.siRNA mediated down-regulation of COX-2 led to a reduced expression of NF-κB and Snail,but an increased expression of E-cadherin in SGC-7901 cells.siRNA mediated down-regulation of NF-κB also led to a reduced expression of E-cadherin and Snail in SGC-7901 cells.However,COX-2 expression did not alter after cells were treated with NF-κB specific siRNA in SGC-7901 cells.Treatment of SGC-7901 cells with celecoxib led to a reduced expression of Snail but an increased expression of E-cadherin.In contrast,treatment of SGC-7901 cells with PGE2 led to an increased Snail and a decreased E-cadherin.However,siRNAmediated knockdown of NF-κB partially abolished the effect of celecoxib and PGE2 on the regulation of E-cadherin and Snail in SGC-7901 cells.CONCLUSION:COX-2 likely functions upstream of NF-κB and regulates the expression of E-cadherin via NF-κB/Snail signaling pathway in gastric cancer cells.     

白细胞介素-2及其受体与乙型肝炎疫苗接种无、弱应答发生的关系

目的：探讨白细胞介素-2（IL-2）与可溶性白细胞介素-2受体（sIL-2R）与乙型肝炎疫苗接种无、弱应答的关系。 方法：在HBsAg和植物血凝素（phytohaemagglutinin,PHA）两种刺激条件下,对21名乙型肝炎疫苗接种无、弱应答者、22名强应答者和21名HBsAg慢性携带者的外周血单个核细胞进行体外培养,并用酶联免疫法测定细胞培养上清液中IL-2和sIL-2R的水平。 结果：无、弱应答组的IL-2水平明显低于强应答组（t＝8.80,P＜0.001＝,而与HBsAg慢性携带组相近（q＝0.06, P＞0.5）。无、弱应答组和强应答组的sIL-2R水平差异无显著意义。结论：外周血单个核细胞分泌IL-2 水平低下可能是乙型肝炎疫苗接种后无、弱应答发生的原因之一。