Modifications in Rat Testicular Morphology and Increases in IFN-γ Serum Levels by the Oral Administration of Subtoxic Doses of Mercuric Chloride

Mercury induces structural and functional damage in several organs, however the effects of subtoxic doses of the metal on the male reproductive system are not well defined. In order to analyze testicular and epididymal morphological alterations and changes in IL-4 or IFN-γ serum levels, adult male Sprague-Dawley rats received 0.01, 0.05 or 0.1?μg/ml of mercuric chloride (HgCl₂) in deionized water for 1 to 7 months by oral route. Controls received deionized water alone. Twenty rats, separated in four groups of five animals each, were used per time of exposure. Progressive degenerative lesions consisting of lack of germ cell cohesion and desquamation, arrest at spermatocyte stage and hypospermatogenesis were observed in seminiferous epithelium by light and electron microscopy. Leydig cells showed cytoplasmic vacuolation and nuclear signs of cell death. Loss of peritubular cell aggregation was evidenced in the epididymis. Mercury accumulation was detected in both organs by mass spectroscopy. Rats showed enhanced IFN-γ serum levels as compared to controls but only reached significance after 7 months of mercury administration. Subtoxic doses of inorganic mercury could lead to reproductive and immunological alterations. The results demonstrate that sublethal concentrations of mercuric chloride are enough to induce morphological and ultrastructural modifications in male reproductive organs. These contribute to functional alterations of spermatogenesis with arrest at spermatocyte stage, hypospermatogenesis and possibly impaired steroidogenesis which together could affect male fertility.     

CagA的表达对慢性胃炎Th细胞亚群分化的影响*

目的探讨幽门螺杆菌CagA的表达对慢性胃炎患者胃黏膜Th细胞亚群分化的影响。方法80例慢性胃炎患者,ELISA法测定血清CagA抗体,根据结果将慢性胃炎患者分为CagA阳性和阴性组,均取患者胃黏膜行病理检查及PCR、Western blot检测核转录因子TBX21、GATA-3、FoxP3和Rorγt的表达水平。结果 CagA抗体阳性组和阴性组分别为52例和28例,CagA抗体阳性组炎症中、重度43例（82.7%）显著高于阴性组10例（35.7%）,差异有统计学意义（χ2=17.964,P<0.05）;2组间Hp菌密度差异无统计学意义。CagA抗体阳性组TBX21、Rorγt的转录及蛋白表达水平较阴性组显著下调,而GATA-3、FoxP3的转录及蛋白表达水平较阴性组显著上调。结论慢性胃炎CagA阳性患者的胃黏膜炎症程度更重,但机体却不能有效清除Hp在胃黏膜中的定植,其原因与可能存在Th0向Th2/Treg的分化偏倚有关。     

Graptopetalum paraguayense and resveratrol ameliorates carboxymethyllysine (CML)-induced pancreas dysfunction and hyperglycemia

Hyperglycemia is associated with advanced glycation end products (AGEs). Recently, AGEs were found to cause pancreatic damage, oxidative stress, and hyperglycemia through the AGE receptor. Carboxymethyllysine (CML) is an AGE but whether it induces pancreatic dysfunction remains unclear. Graptopetalum paraguayense, a vegetable consumed in Taiwan, has been used in folk medicine and is an antioxidant that protects against liver damage. We investigated the protective properties of G. paraguayense 95% ethanol extracts (GPEs) against CML-induced pancreatic damage. The results indicated that resveratrol, GPE, and gallic acid (the active compound of GPE) increased insulin synthesis via upregulation of pancreatic peroxisome proliferator activated-receptor-γ (PPARγ) and pancreatic-duodenal homeobox-1 (PDX-1) but inhibited the expression of CML-mediated CCAAT/enhancer binding protein-β (C/EBPβ), a negative regulator of insulin production. Moreover, resveratrol and GPE also strongly activated nuclear factor-erythroid 2-related factor 2 (Nrf2) to attenuate oxidative stress and improve insulin sensitivity in the liver and muscle of CML-injected C57BL/6 mice and resulted in reduced blood glucose levels. Taken together, these findings suggested that GPE and gallic acid could potentially be used as a food supplement to protect against pancreatic damage and the development of diabetes.     

五加减正气散化裁对溃疡性结肠炎大鼠干扰素-γ的影响

目的:讨论五加减正气散化裁对溃疡结肠炎(UC)大鼠血中的干扰素-γ(INF-γ)的影响。方法:实验动物分成4组,分别为空白组、模型组、西药组和中药组,采用乙酸诱导法造模,观察大鼠结肠黏膜病理变化,用ELISA法检测大鼠血中INF-γ的水平。结果:空白组大鼠血中INF-γ和结肠黏膜无变化,模型组的大鼠血中INF-γ和结肠黏膜变化明显,西药组与中药组大鼠血中INF-γ和结肠黏膜无明显变化。西药组、中药组与空白组间差异无统计学意义;模型组与空白组比较,大鼠血清中INF-γ显著升高,结肠黏膜充血、水肿、糜烂并有溃疡形成,两者之间差异有统计学意义(P<0.05);模型组与西药组、中药组间大鼠血清中INF-γ显著升高,结肠黏膜充血、水肿、糜烂并有溃疡形成,差异有统计学意义(P<0.05)。结论:五加减正气散化裁能干预实验性UC大鼠血中的INF-γ的活性,对UC大鼠结肠溃疡面有修复和保护作用。     

烟草烟雾对大鼠胸主动脉硫化氢/胱硫醚-γ-裂解酶体系的影响

目的探讨烟草烟雾对大鼠胸主动脉硫化氢(H2S)/胱硫醚-γ-裂解酶(CSE)体系的影响。方法以10周龄SD大鼠为研究对象,随机分为对照组、短期吸烟组、中期吸烟组和长期吸烟组。采用烟草烟雾熏吸方法建立被动吸烟大鼠模型,采用敏感硫电极法测定血清中H2S浓度,采用免疫组织化学染色和显微图像定量分析法观察胸主动脉平滑肌CSE的表达。结果短期吸烟组血清H2S浓度与对照组比较无统计学差异(P>0.05),长期吸烟组、中期吸烟组血清H2S浓度明显低于对照组和短期吸烟组(P<0.01),长期吸烟组血清H2S浓度明显低于中期吸烟组(P<0.05),H2S浓度随着烟草烟雾熏吸时间的延长而降低,并呈时间依赖性。短期吸烟组胸主动脉CSE面积密度和光密度与对照组比较无统计学差异(P>0.05),长期吸烟组、中期吸烟组胸主动脉CSE面积密度和光密度明显低于对照组和短期吸烟组(P<0.05),长期吸烟组胸主动脉CSE面积密度和光密度明显低于中期吸烟组(P<0.05),CSE的表达随着烟草烟雾熏吸时间的延长而降低,并呈时间依赖性。结论烟草烟雾可显著下调大鼠血清H2S的浓度及胸主动脉中CSE的表达。     

Suppression of Human Liver Cancer Cell Migration and Invasion via the GABAA Receptor

Objective To investigate the roles of theγ-aminobutyric acid(GABA) in the metastasis of hepatocellular carcinoma(HCC) and to explore the potential of a novel therapeutic approach for the treatment of HCC. Methods The expression levels of GABA receptor subunit genes in various HCC cell lines and patients’ tissues were detected by quantitative real-time polymerase chain reaction and Western blot analysis.Transwell cell migration and invasion assays were carried out for functional analysis.The effects of GABA on liver cancer cell cytoskeletal were determined by immunofluorescence staining. And the effects of GABA on HCC metastasis in nude mice were evaluated using an in vivo orthotopic model of liver cancer. Results The mRNA level of GABA receptor subunits varied between the primary hepatocellular carcinoma tissue and the adjacent non-tumor liver tissue.GABA inhibited human liver cancer cell migration and invasion via the ionotropic GABAa receptor as a result of the induction of liver cancer cell cytoskeletal reorganization.Pretreatment with GABA also significantly reduced intrahepatic liver metastasis and primary tumor formation in vivo. Conclusions These findings introduce a potential and novel therapeutic approach for the treatment of cancer patients based on the modulation of the GABAergic system.     

Pharmacological approaches to mitigate neuroinflammation in Alzheimer’s disease

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases characterized by the formation of extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). Growing evidence suggested that there is an association between neuronal dysfunction and neuroinflammation (NI) in AD, coordinated by the chronic activation of astrocytes and microglial cells along with the subsequent excessive generation of the proinflammatory molecule. Therefore, a better understanding of the relationship between the nervous and immune systems is important in order to delay or avert the neurodegenerative events of AD. The inflammatory/immune pathways and the mechanisms to control these pathways may provide a novel arena to develop new drugs in order to target NI in AD. In this review, we represent the influence of cellular mediators which are involved in the NI process, with regards to the progression of AD. We also discuss the processes and the current status of multiple anti-inflammatory agents which are used in AD and have gone through or going through clinical trials. Moreover, new prospects for targeting NI in the development of AD drugs have also been highlighted.