The neuroprotective role of microglial cells against amyloid beta‐mediated toxicity in organotypic hippocampal slice cultures

During Alzheimer’s disease (AD) progression, microglial cells play complex roles and have potentially detrimental as well as beneficial effects. The use of appropriate model systems is essential for characterizing and understanding the roles of microglia in AD pathology. Here, we used organotypic hippocampal slice cultures (OHSCs) to investigate the impact of microglia on amyloid beta (Aβ)‐mediated toxicity. Neurons in OHSCs containing microglia were not vulnerable to cell death after 7 days of repeated treatment with Aβ_1‐42 oligomer‐enriched preparations. However, when clodronate was used to remove microglia, treatment with Aβ_1‐42 resulted in significant neuronal death. Further investigations indicated signs of endoplasmic reticulum stress and caspase activation after Aβ_1‐42 challenge only when microglia were absent. Interestingly, microglia provided protection without displaying any classic signs of activation, such as an amoeboid morphology or the release of pro‐inflammatory mediators (e.g., IL‐6, TNF‐α, NO). Furthermore, depleting microglia or inhibiting microglial uptake mechanisms resulted in significant more Aβ deposition compared to that observed in OHSCs containing functional microglia, suggesting that microglia efficiently cleared Aβ. Because inhibiting microglial uptake increased neuronal cell death, the ability of microglia to engulf Aβ is thought to contribute to its protective properties. Our study argues for a beneficial role of functional ramified microglia whereby they act against the accumulation of neurotoxic forms of Aβ and support neuronal resilience in an in situ model of AD pathology.     

The heterogeneous immune microenvironment in breast cancer is affected by hypoxia-related genes

The immune system constitutes an important first-line defence against malignant transformation. However, cancer mediated immunosuppression inactivates the mechanisms of host immune surveillance. Cancer cells shut down anti-cancer immunity through direct cell–cell interactions with leukocytes and through soluble factors, establishing an immunosuppressive environment for unimpeded cancer growth. The composition of the immunosuppressive microenvironment in breast tumours is not well documented. To address this question, selected immunosuppressive factors were analyzed in tumour specimens from 33 breast cancer patients after surgery. The mRNA expression of selected genes was quantified in fresh tumour samples. Tumour infiltrating leukocytes were characterized by flow cytometry to identify regulatory T cells, myeloid derived suppressor cells, and type 2 macrophages. Statistical analysis revealed several interesting correlations between the studied parameters and clinical features. Overall, a surprisingly high degree of heterogeneity in the composition of the immunosuppressive environment was found across all breast cancer samples which adds to the complexity of this disease. The influence of the hypoxia inducible factors (HIFs) on the immune microenvironment was also addressed. The level of HIFs correlated with hormone receptor status and the expression of several immunosuppressive molecules. Targeting HIFs might not only sensitize breast tumours for radiation and chemotherapies but also interfere with cancer immunosuppression.     

Myeloperoxidase gene polymorphism predicts fibrosis severity in women with hepatitis C

Oxidative stress plays an important role on liver fibrosis progression in the course of hepatitis C virus (HCV) infection. Myeloperoxidase (MPO) is an enzyme released by neutrophils and macrophages, responsible for generating hypochlorous acid and reactive oxygen species (ROS) that may lead to liver injury in HCV infection. On the other hand, antioxidant enzymes such as manganese superoxide dismutase (SOD) controls ROS-mediated damage. The aim of the present study was to investigate the influence of MPO G-463A and SOD2 Ala16Val polymorphisms in the severity of liver fibrosis in individuals with chronic HCV infection. The present study included 270 patients with chronic HCV recruited from the Gastrohepatology Service of the Oswaldo Cruz University Hospital/Liver Institute of Pernambuco (Recife, Northeastern Brazil). All patients underwent liver biopsy, which was classified according METAVIR score. The SNPs were determined by real-time PCR. After multivariate analysis adjustment, the GG genotype of MPO and the presence of metabolic syndrome were independently associated with fibrosis severity in women (P = 0.025 OR 2.25 CI 1.10–4.59 and P = 0.032 OR 2.32 CI 1.07–5.01, respectively). The presence of the GG genotype seems to be a risk factor for fibrosis severity in women with HCV.     

78例乳腺癌的nm23基因和ER表达及其临床意义

目的研究nm23和ER在乳腺癌组织中的表达及与转移的关系。方法采用免疫组化法（S—P法）,对2000～2005年我科诊断的78乳腺癌患者的病理切片做回顾性分析。结果nm23、ER在无淋巴结转移的乳腺癌组阳性表达分别为84．4％、78．1％,明显高于有淋巴结转移的乳腺癌组（P〈0．01）。组织学分级中,分化程度越高,nm23、ER的阳性率越高（P〈0．01和P〈0．05）。结论乳腺癌的nm23和ER阳性表达率无淋巴结转移组明显高于有淋巴结转移组。nm23、ER阳性的乳腺癌分化较高,淋巴结转移发生较晚,预后较好。nm23和ER可作为判断乳腺癌预后的指标。     

Self-introduction of a two-meter nylon string into the urinary bladder: A case report

A foreign body of the urinary bladder can be caused by several factors. Several patients deliberately insert foreign bodies via the urethra due to psychiatric issues to achieve sexual pleasure. Self-inserted urinary bladder foreign bodies remain a significant challenge in the urology field regarding diagnosis and management as patients may be late in seeking medical assistance due to guilt and embarrassment. We aimed to report a 37-year-old man who inserted a two-meter nylon string into his urethra for sexual gratification.     

Adaptive response of resistant cancer cells to chemotherapy

Despite advances in cancer therapeutics and the integration of personalized medicine, the development of chemoresistance in many patients remains a significant contributing factor to cancer mortality. Upon treatment with chemotherapeutics, the disruption of homeostasis in cancer cells triggers the adaptive response which has emerged as a key resistance mechanism. In this review, we summarize the mechanistic studies investigating the three major components of the adaptive response, autophagy, endoplasmic reticulum (ER) stress signaling, and senescence, in response to cancer chemotherapy. We will discuss the development of potential cancer therapeutic strategies in the context of these adaptive resistance mechanisms, with the goal of stimulating research that may facilitate the development of effective cancer therapy.     

乳腺癌中MTA1，ER的表达及其相关性研究

目的 观察MTA1,ER在乳腺癌中的表达,探讨两者与乳腺癌侵袭能力的相关性.方法 应用原位核酸分子杂交和免疫组织化学分别检测正常乳腺组织、癌前病变组织及乳腺癌组织中MTA1,ER的表达;并以Spearman等级相关分析它们的相关性.结果 在正常乳腺组织、癌前病变组织、乳腺癌组织中,原位杂交对MTA1,ER的阳性检出率高于免疫组化,原位杂交检测中MTA1 mRNA的表达率分别为12.2%,33.3%,81.1%;免疫组化检测中MTA1的表达率分别为11.1%,31.1%,72.2%;原位杂交检测中ER mRNA的表达率分别为83.3%.61.1%,37.8%,免疫组化检测中ER的表达率分别为70.9%,56.7%和35.6%.MTA1在ER阴性组中的阳性表达率为86.2%,高于阳性组中的46.9%.结论 原位杂交和免疫组化联合检测增加MTA1,ER基因的检出率;随疾病的进展和肿瘤分化程度的降低,MTA1表达逐渐增强,ER表达逐渐减弱,甚至丧失.MTA1与ER表达呈负相关(r=-0.466,P＜0.01).提示MTA1,ER可作为乳腺癌预后及治疗重要的分子标记物.     

抗乳增片对乳腺增生模型大鼠脏器系数及乳腺组织ER、PR表达的影响

[目的]观察抗乳增片对乳腺增生模型大鼠脏器系数和乳腺组织ER、PR的影响。[方法]采用去卵巢加注射苯甲酸雌二醇的方法造成大鼠乳腺增生模型,给予不同剂量的抗乳增片治疗4周。动物处死后取脾、胸腺称重并计算脏器指数;采用免疫组化方法观察乳腺组织中雌激素受体(ER)和孕激素受体(PR)的变化。[结果]模型组大鼠脾脏指数、胸腺指数较假手术组均降低,各用药组的2个脏器指数较模型组显著升高(P<0.05或P<0.01);模型组大鼠乳腺组织ER、PR较假手术组表达增强,与模型组相比,各药物治疗组大鼠乳腺组织ER和PR表达的积分值显著减少(P<0.05或P<0.01)。[结论]抗乳增片对大鼠乳腺增生的治疗作用与其能够增强其免疫功能、降低乳腺组织ER、PR表达有关。