Phenotypic and metabolic aspects of prostatic epithelial cells in aged gerbils after antisteroidal therapy: Turnover in the state of chromatin condensation and androgen-independent cell replacement

The gerbil is a rodent considered a good model for studies of prostatic morphophysiology under different experimental conditions. Studies involving castration and steroidal blockers of aged gerbils showed that the glandular epithelium persists after long-term therapy, preventing the organ atrophy. Thus, the objective of this study was to evaluate the phenotypic characteristics and behavior of prostatic epithelial cells that remained after different periods of hormone ablation in aged gerbils. The identification of elements that influenced the survival of this cell type was performed by morphometric, nuclear phenotypes, ultrastructural and immune histochemical analysis. The most significant responses to treatment, by analyzing morphometric features, were observed during the first three time points (day 1, day 3, and day 7), after which there appeared to be an adjustment of the gland to the hormone ablation. All treatments led to changes in the state of chromatin condensation, DNA methylation pattern and phenotypic changes indicated cell senescence. Additionally, an increase in the basal cells seemed to guarantee self-renewal properties to the epithelium. These data indicate that changes occur at many levels, including gene expression and nuclear architecture in the epithelial cells, when aging and steroidal blockade are associated. These aspects are important when considering castration-resistant prostate cancer, a malignant tumor posing difficult therapeutic intervention.     

Biochemical and immunohistochemical changes in delta-9-tetrahydrocannabinol-treated type 2 diabetic rats

The regulation of glucose, lipid metabolism and immunoreactivities of insulin and glucagon peptides by delta-9-tetrahydrocannabinol (Δ⁹-THC) in diabetes were examined in an experimental rat model. Male Sprague-Dawley rats were divided into four groups: (1) control, (2) Δ⁹-THC treated, (3) diabetic, and (4) diabetic + Δ⁹-THC. The type 2 diabetic rat model was established by intraperitoneal (i.p.) injection of nicotinamide (85 mg/kg body weight) followed after 15 min by i.p. injection of streptozotocin (STZ) at 65 mg/kg of body weight. Δ⁹-THC and Δ⁹-THC treated diabetic groups received 3 mg/kg/day of Δ⁹-THC for 7 days. The immunolocalization of insulin and glucagon peptides was investigated in the pancreas using a streptavidin–biotin–peroxidase technique. High density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), very low density lipoprotein cholesterol (VLDL), triglycerides (TG), total cholesterol (TC) and total protein (TP) levels were measured in serum. Total islet area percent of insulin immunoreactive cells slightly changed in diabetic + Δ⁹-THC rats compared to diabetic animals. However, the area percent of glucagon immunoreactive cells showed a decrease in diabetic + Δ⁹-THC rats compared to that of diabetic animals alone. Serum TC, HDL and LDL levels of diabetes + Δ⁹-THC group showed a decrease compared to the diabetic group. These results indicate that Δ⁹-THC may serve a protective role against hyperlipidemia and hyperglycemia in diabetic rats.     

Repeated Baclofen treatment ameliorates motor dysfunction,suppresses reflex activity and decreases the expression of signaling proteins in reticular nuclei and lumbar motoneurons after spinal trauma in rats

The interruption of supraspinal input to the spinal cord leads to motor dysfunction and the development of spasticity. Clinical studies have shown that Baclofen (a GABA_B agonist), while effective in modulating spasticity is associated with side-effects and the development of tolerance. The aim of the present study was to assess if discontinued Baclofen treatment and its repeated application leads antispasticity effects, and whether such changes affect neuronal nitric oxide synthase (nNOS) in the brainstem, nNOS and parvalbumin (PV) in lumbar α-motoneurons and glial fibrillary acidic protein in the ventral horn of the spinal cord. Adult male Wistar rats were exposed to Th9 spinal cord transection. Baclofen (30 mg/b.w.) diluted in drinking water, was administered for 6 days, starting at week 1 after injury and then repeated till week 4 after injury. The behavior of the animals was tested (tail-flick test, BBB locomotor score) from 1 to 8 weeks. Our results clearly indicate the role of nitric oxide, produced by nNOS in the initiation and the maintenance of spasticity states 1, 6 and 8 weeks after spinal trauma. A considerable decrease of nNOS staining after Baclofen treatment correlates with improvement of motor dysfunction. The findings also show that parvalbumin and astrocytes participate in the regulation of ion concentrations in the sub-acute phase after the injury.     

TNF-α抗体对Sp1和NF-κ B p65在兔粘连腹膜表达的影响

目的探讨TNF-α抗体对实验兔腹膜损伤粘连修复演变过程中核转录因子Sp1和NF-κB p65活化的影响。方法实验兔随机分3组:正常对照组(不做任何处理)、模型组(腹膜腔内注入生理盐水)、TNF-α抗体组(造模后后腹膜腔内注入TNF-α抗体),每组30只,共90只。建立实验兔腹膜回盲部手术动物模型,ELISA检测腹水Sp1、NF-κB p65的表达,Masson染色检测Sp1在腹膜的表达、免疫组化SP法检测NF-κB p65在腹膜的表达,监测腹膜粘连分级变化。结果 TNF-α抗体导致Sp1和NF-κB p65在损伤腹膜和腹水中的表达水平显著减低(0.01),并有效减轻腹膜粘连形成。结论 TNF-α抗体有效减轻腹膜粘连形成可能与其下调Sp1和NF-κB p65表达相关。     

A Study of Diphenylfumaronitrile and Furan‐Substituted Diketopyrrolopyrrole Alternating Copolymer and Its Thin‐Film Transistors

A fused aromatic furan‐substituted diketopyrrolopyrrole and novel diphenylfumaronitrile conjugated building blocks are used for the synthesis of an alternating copolymer ( DPFN‐DPPF ) via Suzuki polycondensation. In this paper, the first attempt to use the diphenylfumaro­nitrile building block for the synthesis of conjugated polymer is described. The number‐average and weight‐average ­molecular weights calculated for DPFN‐DPPF are 20 661 and 66 346 g mol^?1, respectively. The optical bandgap calculated for DPFN‐DPPF is 1.53 eV whereas the highest occupied molecular orbital (HOMO) value calculated by photoelectron spectroscopy in air (PESA) is 5.50 eV. The calculated HOMO value is lower, which is suitable for stable organic electronic devices. DPFN‐DPPF polymer is used as an active layer in bottom‐contact bottom‐gate organic thin‐film transistor devices and the thin film exhibits a hole mobility of 0.20 cm² V^?1 s^?1 in air.

     

TNF and MAP kinase signalling pathways

The binding of tumour necrosis factor α (TNFα) to cell surface receptors engages multiple signal transduction pathways, including three groups of mitogen-activated protein (MAP) kinases: extracellular-signal-regulated kinases (ERKs); the cJun NH₂-terminal kinases (JNKs); and the p38 MAP kinases. These MAP kinase signalling pathways induce a secondary response by increasing the expression of several inflammatory cytokines (including TNFα) that contribute to the biological activity of TNFα. MAP kinases therefore function both upstream and down-stream of signalling by TNFα receptors. Here we review mechanisms that mediate these actions of MAP kinases during the response to TNFα.     

重症肺炎肺泡灌洗液微小核糖核酸-127的表达水平及临床意义

目的:探讨重症肺炎患者肺泡灌洗液(BALF)中微小核糖核酸-127-5p(miRNA-127-5p)的表达水平及临床价值。方法:选取我院2017年1月至2019年5月重症肺炎患者102例进行分析。所有患者第1天行纤维支气管镜检查;在病程第4、7天经纤维支气管进行支气管肺泡灌洗(BAL);选择右肺中叶或左上叶舌段,注入0.9%氯化钠液之后,使用合适的负压(100 mm Hg,1 mm Hg=0.133 k Pa)吸取BALF;应用聚合酶链式反应(PCR)法检测miR-127-5p表达量;采用酶联免疫吸附实验(ELISA)法对BALF中IL-6、IL-8及IL-10水平进行测定。结果:动态监测两组患者BALF中的miRNA-127-5p表达量以及IL-6、IL-8及IL-10水平;治疗第1天,两组的miRNA-127-5p表达量以及IL-6、IL-8及IL-10水平,差异无统计学意义(P>0.05);治疗第4天,预后良好组的miRNA-127-5p表达量显著高于预后不良组,差异有统计学意义(P<0.05);治疗第4天,预后良好组的IL-8,IL-10水平显著低于预后不良组,差异有统计学意义(P<0.05);治疗第7天,预后良好组的miRNA-127-5p表达量显著高于预后不良组,差异有统计学意义(P<0.05);治疗第7天,预后良好组的IL-8,IL-10水平显著低于预后不良组,差异有统计学意义(P<0.05);经治疗,两组的miRNA-127-5p表达量逐渐升高,IL-8,IL-10水平逐渐降低。miRNA-127-5p表达量在预测重症肺炎患者预后情况的AUC曲线下面积为(敏感度=88.6%,特异性=70.9%)。结论:肺泡灌洗液中miRNA-127-5p表达量有望成为一种判断重症肺炎患者的预后的新型生物标志物。     

错配修复蛋白和p53蛋白在结直肠癌中的表达及其临床意义

背景:研究表明,结直肠癌的主要发病途径有两条,即染色体不稳定性途径和微卫星不稳定性(MSI)途径。目的:探讨错配修复蛋白(MMRP)和p53蛋白在结直肠癌中的表达及其临床意义。方法:采用免疫组化SP法检测2013年1月—2017年12月上海市嘉定区中心医院收治的276例结直肠癌中4种MMRP和p53蛋白表达,并分析其与临床病理特征的关系。分析MSI对结直肠癌患者生存情况的影响。结果:MMRP表达缺失36例(13.0%),MSI与组织病理学类型、TNM分期和血吸虫感染有关(P<0.05),而与患者性别、年龄、发病部位、分化程度和淋巴结转移均无关(P>0.05)。p53蛋白在结直肠癌中的阳性表达率为44.9%,其表达与组织病理学类型、TNM分期、淋巴结转移和血吸虫感染有关(P<0.05),而与患者性别、年龄、发病部位和分化程度均无关(P>0.05)。MSI与p53表达呈负相关(r=-0.169,P<0.05)。MSI组和MSS组的1、3、5年生存率分别为100%、97.2%、83.1%和96.7%、81.9%、38.9%,差异有统计学意义(χ^2=12.582,P=0.001)。结论:MSI和p53表达与结直肠癌的临床病理特征关系密切,对肿瘤的恶性程度和预后的判断有指导意义。MSI与p53表达呈负相关,提示两者可能参与结直肠癌不同阶段的发生、发展过程。