Cigarette smoking decreases TGF-β1 serum concentrations after long bone fracture

TGF-β1 serum concentrations are considered to be one of the most promising markers of fracture healing. Previously, we demonstrated significant differences in the post-traumatic time courses of patients with timely and delayed fracture healing. The aim of this study was to evaluate possible differences in the serum concentrations of TGF-β1 in cigarette-smoking vs. non-smoking patients with timely and delayed fracture healing in order to understand pathophysiological pathways through which smoking impairs fracture healing.Serum samples were collected from 248 patients undergoing surgical treatment for long bone fractures within 1 year of surgery. Samples from 14 patients with atrophic-type delayed fracture healing were compared with 14 matched patients with normal bone healing. Each group included seven smokers and seven non-smokers. Post-operative serum concentrations were analysed at 1, 2, 4, 8, and 12 weeks as well as 1 year after surgery. The patients were monitored both clinically and radiologically for the entire duration of the study.All patients increased TGF-β1 serum concentrations after surgery. In patients with normal fracture healing, significantly higher TGF-β1 levels were observed in non-smokers (70 ng/ml) than in smokers (50 ng/ml) at the 4th week after surgery (p = 0.007). Also at the 4th week, in patients with delayed healing, significantly lower TGF-β1 levels were observed in smokers than in non-smokers (38 ng/ml vs. 47 ng/ml, p = 0.021). However, no significant differences between non-smokers with delayed healing and smokers with normal healing (p = 0.151) were observed at the 4th week after surgery. TGF-β1 serum concentrations reached a plateau in all groups from the 6th to the 12th week after surgery, with a slight decrease observed in the final measurement taken 1 year after surgery.This study demonstrates that, after fracture, TGF-β1 serum concentrations are reduced by smoking, and this reduction is statistically significant during the 4th week after surgery. Our findings may help reveal the mechanism by which smoking impairs fracture healing. Furthermore, these results may help to establish a serological marker that predicts impaired fracture healing soon after the injury. Surgeons will not only be able to monitor the bone healing, but they will also be able to monitor the success of additional treatments such as ultrasound and bone morphologic proteins (BMPs).     

慢性牙周炎与慢性肾衰竭动物模型中IL-1β的表达

目的：检测和分析白细胞介素-1β（IL-1β）在大鼠慢性牙周炎（CP）和慢性肾衰竭（CRF）模型中的表达。方法：40只SD大鼠随机分为4组,每组10只,正常对照组,慢性牙周炎组,慢性肾衰竭组,牙周炎＋慢性肾衰竭（复合组）,各组接受相应的建模干预处理。酶联免疫吸附法（ELISA）检测血清IL-1β水平,免疫组化法观察各组肾组织中IL-1β的表达程度,检测肾功能及牙周指标。结果：复合组血清IL-1β水平及肾组织中IL-1β的表达较其他组高（P〈0.05,P〈0.01）,慢性肾衰竭组、复合组血肌酐（Scr）、尿素氮（BUN）高于对照组、慢性牙周炎组（P〈0.05）。慢性牙周炎组、复合组牙龈附着丧失（AL）高于对照组、慢性肾衰竭组（P〈0.05）。结论：CP与CRF之间可能具有相关性,IL-1β的表达可能与两疾病的发生发展有关。     

白介素-1β对小鼠着床窗口期子宫内膜上皮细胞分泌基质金属蛋白酶-9及细胞黏附分子-1的影响

目的 研究白介素-1β（IL-1β）对小鼠着床窗口期子宫内膜上皮细胞分泌金属蛋白酶-9（MMP-9）及细胞黏附分子-1（ICAM-1）的影响.方法 离体培养着床窗口期小鼠子宫内膜上皮细胞,用IL-1β作为处理因素,通过免疫组织化学SP法对子宫内膜上皮细胞MMP-9、ICAM-1蛋白的表达进行检测.结果 随着IL-1β浓度的增加,原代培养的子宫内膜上皮细胞分泌MMP-9及ICAM-1表达量均呈浓度依赖性升高（P〈0.05）.结论 一定水平的IL-1β可以促进子宫内膜上皮细胞MMP-9及ICAM-1的分泌,有利于胚胎着床.     

Facilitating antidepressant-like actions of estrogens are mediated by 5-HT1A and estrogen receptors in the rat forced swimming test

Previous studies have shown that 17beta-estradiol (E2) induces antidepressant-like actions per se and potentiates those produced by fluoxetine (FLX) in the forced swimming test (FST). The aim of the present work was to explore the participation of serotonin 1A receptors (5-HT1A) and estrogen receptors (ERs) in the antidepressant-like actions of E2, FLX or their combination in the FST. Although all antidepressants reduce behavioral immobility, antidepressants that modulate serotonergic neurotransmission increase swimming behavior whereas those that modulate the catecholaminergic neurotransmission increase climbing behavior. Thus, using this animal model, it is possible to infer which neurotransmitter system is modulating the action of an antidepressant compound. Ovariectomized female Wistar rats were used in all experiments. In the first experiment, an effective dose of E2 (10 microg/rat, -48 h) was combined with several doses (0.5, 1.0 and 2 mg/kg) of RU 58668 (a pure ER antagonist) 48 h previous to the FST. The second experiment evaluated the action of (1 mg/kg, -48 h or -23, -5 and -1 h) WAY 100635 (5-HT1A receptor antagonist) on the antidepressant-like action of FLX (10 mg/kg, -23, -5 and -1 h). In the third experiment, the effect of RU 58668 (2 mg/kg, -48) or WAY 100635 (1 mg/kg, -48 h) on the antidepressant-like action of the combination of a sub-optimal dose of E2 (2.5 microg/rat, -48 h) plus a non-effective dose of FLX (2.5 mg/kg, -23,-5 and -1 h) was evaluated. The results showed that RU 58668, the antagonist to the ER, canceled the antidepressant-like action of E2 in a dose-dependent manner. The antagonist to the 5-HT1A receptor blocked the antidepressant action of FLX only when administered simultaneously with FLX, i.e. -23, -5 and -1 h before the FST. Finally, the administration of both RU 58668, and WAY100635 canceled the antidepressant-like action of the combination of E2/FLX. These results imply that both 5-HT1A receptors and ERs participate in the facilitating actions of E2 on the antidepressant-like action of FLX in the FST.     

大鼠慢性皮肤溃疡创面愈合中转化生长因子-β1、胶原Ⅰ、胶原Ⅲ的蛋白表达

目的 观察大鼠慢性皮肤溃疡创面愈合过程中转化生长因子-β1( TGF-β1)、胶原Ⅰ和胶原Ⅲ的蛋白表达。方法 将24只8周龄雌性Wister大鼠分为单纯创面组(A组)和皮瓣+创面组即缺血模型组(B组),每组各12只;苏木素-伊红(HE)染色法观察创面1、3、7、10d上皮化率、收缩率及中性粒细胞;采用酶联免疫吸附试验(ELISA)方法测定创面1、3、7、10 d TGF-β1、Ⅰ型和Ⅲ型胶原的蛋白表达。结果 A组上皮化率在各个时间段均高于B组,且在第7天差异有统计学意义(P＜0.05)。A组收缩率明显低于B组。A组中性粒细胞第1、3天逐渐增加,第3天增加到最多,随后逐渐减少;B组在1、3、7d出现增加趋势,第7天增加到最多,第10天减少。TGF-31含量A组于术后1、3、7、10d呈曲线上升趋势,B组在术后1、3、7d逐渐减低,10 d较7d略有回升,且在第1天两组差异有统计学意义(P＜0.05)。胶原Ⅰ蛋白的含量两组随着术后时间的延长均呈减少趋势,在第10天两组差异有统计学意义(P＜0.05)。胶原Ⅲ蛋白的含量两组随术后时间的延长也呈减少的趋势,但在第3天A组比B组明显增加,差异有统计学意义(P＜0.05)。结论 在缺血的干预因素作用下TGF-β1、Ⅰ型和Ⅲ型胶原蛋白表达的减少可能延迟了慢性创伤的正常愈合。     

N-cadherin、 β-连环素在肝癌组织中的表达及与Wnt信号途径的关系

目的 观察肝癌(HCC)中N-cadherin分子是否调控β-连环素(β-catenin)的表达及Wnt信号途径的活化。方法 免疫组织化学分析64例肝癌组织中N-cadherin及β-catenin的表达及相互关系。调控肝癌细胞株HCCLM3、SMMC-7721中N-cadherin表达并检测β-catenin的表达及Wnt信号途径的活化。结果 64例肝癌中,N-cadherin表达缺失34例;β-catenin在细胞膜上表达,无细胞核内聚集,且13例细胞膜表达缺失;细胞膜上β-catenin表达缺失与N-cadherin表达缺失呈正相关(P＜0.05)。下调HCCLM3细胞或上调SMMC-7721细胞中的N-cadherin表达导致细胞膜上β-catenin表达减弱或增强,但均未导致Wnt信号途径的活化。结论 在肝癌中,N-cadherin表达与细胞膜上β-catenin的表达水平呈正相关,但N-cadherin分子并不参与Wnt信号途径的调控。     

转化生长因子-β1及凋亡相关因子在泡球蚴感染宿主病灶旁免疫细胞中的表达及其意义

目的 探讨泡球蚴感染宿主病灶旁免疫细胞中转化生长因子-β1(TGF-β1)、凋亡及相关因子Caspase-3的变化及其意义.方法 8例配对泡型包虫患者和泡球蚴感染小鼠均采用苏木素-伊红(HE)染色观察病理变化,免疫组织化学技术检测病灶旁免疫细胞TGF-β1以及凋亡相关因子Caspase-3的表达与分布,原位末端标记技术(TUNEL)检测病灶旁免疫细胞凋亡.结果 泡型包虫患者及泡球蚴感染小鼠病灶旁及汇管区均有大量炎性细胞灶性浸润,TGF-β1(P＜0.01)和凋亡相关因子Caspase-3(P＜0.01)高表达,TUNEL结果表明病灶旁免疫细胞发生凋亡,与对照比较差异有统计学意义(P＜0.01).结论 泡球蚴在感染宿主过程中可能通过引起宿主TGF-β1高表达,造成免疫细胞发生凋亡而达到逃避宿主免疫反应长期寄生的目的.

Abstract：

Objective To explore the expression of transforming growth factor-pi (TGF-β1 ) and Caspase-3 in immune cells adjacent to Echinococcus multilocularis (Em) invasion. Methods In 8 paired alveolar echinococcoisis (AE) patients and Em infected mice, pathological changes were observed by Hematoxylin and Eosin (HE) staining. The expression of TGF-β1 and Caspase-3 in immune cells was detected by using immunohistochmistry, and the apoptosis of the immune cells was assayed by TUNEL. Results As compared with the lesion and the distant, TGF-β1 expressed mainly around granuloma,showed significant difference: AE leision and distant tissue ( P ＜ 0. 01) , acompanied with the high expression of Caspase-3 in immune cells ( P ＜ 0. 01). The immune cells showed significant apoptosis ( P ＜ 0. 01). The results of Em mouse model were consistent with AE patients. Conclusion TGF-β1 may play an important role in immune cell apoptosis during Em Evasion.     

转化生长因子-β通过PI3K/AKT信号通路促进人肺腺癌细胞株A549的增殖作用

目的 探讨转化生长因子-β(TGF-β)在人肺癌细胞株A549中对细胞增殖的影响及其机制.方法 通过抑制组50例和促进组50例两个方面验证TGF-β对肺癌细胞株A549的促增殖作用,噻唑蓝(MTT)比色法测定细胞增殖速率,流式细胞仪检测细胞的早晚期凋亡和细胞增殖状态.结果 经过siTGF-βR2处理的细胞,细胞增殖率为(91.8±2.3)%,增殖能力明显减弱;而经过rhTGF-β处理的细胞,细胞增殖率为(112.8±5.6)%,增殖能力则明显增强.流式细胞仪结果显示各组的凋亡率分别为:空白组(6.81±0.11)%,随机干扰siRNA组为(6.75±0.12)%,rhTGF-β1组为(6.10±0.10)%,siTGF-βR2组为(7.77±0.09)%,LY294002组为(7.82±0.14)%.结论 TGF-β通过PI3K/AKT信号通路促进人肺腺癌细胞株A549的增殖.

Abstract：

Objective To investigate the effect of transforming growth factor (TGF)-β in human lung cancer cell line A549 on cell proliferation and its mechanism. Methods TGF-β promoted proliferation of human lung cancer cell line A549 (50 cases), which was validated both in respect of inhibition and promotion. Cell proliferation rate was determined by methyl thiazol tetrazolium (MTT). The apotosis and proliferation were analyzed by flow cytometry in early and later stages of cells. Results Cell proliferation rate of A549 ceils was (91.8 ±2.3)%, which was significantly decreased after treatment with siTGF-βR2. On the contrary, the rate was (112. 8 ± 5. 6)%, which was significantly enhanced after treatment with rhTGF-β. Flow cytometry demonstrted that apotosis rate in control group, random interference siRNA group, rhTGF-β1 group, siTGF-βR2 group and LY294002 group was (6. 81 ± 0. 11 )%, (6. 75 ±0.12)%, (6.10±0.10)%, (7.77±0.09)%, and (7.82±0.14)% respectively. Conclusion TGF-β promotes proliferation of human lung adenocarcinoma cell line A549 through the PI3K/AKT pathway.