姜黄素通过上调PPARγ抑制糖基化终末产物诱导的软骨细胞凋亡及线粒体功能损伤

目的观察姜黄素(curcumin)对糖基化终末产物(AGEs)诱导的软骨细胞凋亡及线粒体功能损伤的作用,并探讨相关机制是否与姜黄素上调过氧化物酶体增殖物激活受体-γ(PPARγ)相关。方法原代培养家兔膝关节软骨细胞;TUNEL染色法检测细胞凋亡;Rhodamine-123试剂盒检测线粒体跨膜电位(△Ψm);ATP试剂盒检测线粒体ATP生成;分光光度法检测caspase-3活性;Western blot检测PPARγ、细胞色素C、Bax及Bcl-2蛋白表达;real-time PCR检测PPARγmRNA含量;DNA-binding法检测PPARγ活性。结果 AGEs(200 mg·L-1)可明显诱导兔软骨细胞凋亡,同时线粒体跨膜电位(△Ψm)降低、ATP生成减少,caspase-3活性增加,细胞色素C释放增加,Bax/Bcl-2的比值增加;线粒体通透性转换孔的抑制剂环孢霉素A(Cs A,100 nmol·L-1)可以明显抑制AGEs诱导的细胞凋亡;PPARγ特异性激动剂吡格列酮及姜黄素均可明显抑制AGEs诱导的软骨细胞凋亡及线粒体功能损伤,给予PPARγ特异性抑制剂GW9662 10μmol·L-1预处理后,可以明显拮抗姜黄素的保护作用。同时,姜黄素可以明显上调AGEs诱导的PPARγ活性的降低,并伴随PPARγ相应的mRNA及蛋白表达水平的升高。结论姜黄素通过上调PPARγ,有效地保护AGEs诱导的软骨细胞线粒体损伤,从而抑制AGEs诱导的软骨细胞凋亡。     

(GγAγδβ)0$({}^{\rm G}{\gamma}{}^{\rm A}{\gamma}\delta\beta)^0$-Thalassemia: Report of two cases in a family

Case 1 presented with severe anemia and received an intrauterine blood cell transfusion at 33 weeks of gestation. The anemia spontaneously improved in early infancy. Case 2, the father of Case 1, had an uneventful birth with no evidence of anemia, though microcytic anemia was observed during childhood. The genetic analysis of the β-globin gene cluster identified a novel heterozygous deletion of DNA extending from the Gγ-globin gene downstream to the β-globin gene, confirming a diagnosis of (^Gγ^Aγδβ)⁰-thalassemia. In cases where thalassemia is suspected based on blood tests, a genetic diagnosis should be performed for the sake of the offspring.     

恩替卡韦分散片治疗对高病毒载量慢性乙肝患者的T细胞亚群及血清脂联素、IFN-γ、IL-2水平的影响

目的探讨恩替卡韦分散片(ETV)治疗对高病毒载量慢性乙肝患者的T细胞亚群及血清脂联素(ADP)、干扰素-γ(IFN-γ)、白细胞介素-2(IL-2)水平的影响。方法从本院于2018年6月至2020年6月收治慢性乙肝患者中筛选经荧光定量PCR法测定HBV-DNA>2×10⁵ IU/mL为高病毒载量86例进行研究,按随机数字表法分对照组和观察组,予以对照组常规减黄、保肝及营养支持等对症治疗,观察组在对症治疗基础上予以ETV治疗,均持续治疗6个月,比较两组T细胞亚群、病毒载量指标及Th1/Th2型与相关炎性因子水平。结果经治疗,两组CD3⁺、CD4⁺水平均见提升,CD8⁺水平有一定下降,观察组CD3⁺、CD4⁺水平较对照组更高,CD8⁺水平则更低(P<0.05);两组HBsAg、HBeAg及HBV-DNA载量水平均见相应降低,观察组低于对照组(P<0.05);两组ADP水平呈上升趋势,IFN-γ及IL-2水平均呈下降趋势,观察组ADP水平高于对照组,IFN-γ及IL-2水平均更低(P<0.05)。结论高病毒载量慢性乙肝患者应用恩替卡韦分散片治疗,有助于T细胞亚群改善,且较大程度降低了病毒载量水平,并增强了机体免疫功能。     

醋酸曲安奈德局部注射对变应性鼻炎患者血清白介素4和γ干扰素的影响

目的：评价醋酸曲安奈德局部注射对变应性鼻炎患者血清白介素4（interleukin-4,IL-4）和Y干扰素（interferon-γ,INF-γ）表达水平的影响.方法：60例变应性鼻炎患者随机分成观察组和对照组各30例,对照组予盐酸西替利嗪片10 mg,po,qd,观察组患者双侧中、下鼻甲黏膜下局部注射醋酸曲安奈德治疗.治疗4周后,检测两组患者血清IL-4、IFN-γ水平,比较两组疗效和药品不良反应.结果：观察组总有效率为93.33％,高于对照组的73.33％,但差异无统计学意义（P＞0.05）.治疗4周后,观察组IL-4浓度低于对照组（P＜0.01）,IFN-γ浓度高于对照组（P＜0.01）.两组均未发现不能耐受的不良反应或严重不良反应.结论：醋酸曲安奈德局部注射治疗变应性鼻炎疗效较佳,能够降低患者血清IL-4水平,并提高血清IFN-γ水平.     

参麦注射液对特发性血小板减少性紫癜患者外周血调节性T细胞的影响

目的：探讨参麦注射液对特发性血小板减少性紫癜患者外周血CD4＋CD2＋5 Treg细胞计数和分泌因子水平的影响。方法选取特发性血小板减少性紫癜患者78例,以随机数字表法分为两组;对照组常规泼尼松治疗,观察组在对照组的基础上加用参麦注射液。对比临床疗效,并分别于治疗前后抽取患者空腹静脉血,以流式细胞法测定CD4＋CD＋25FoxP3＋Treg细胞计数,以ELISA试剂盒测定IL-2、IL-4以及IFN-γ血清含量。结果观察组显效率56．41％、总有效率92．31％,均显著高于对照组的30．77％和71．79％（χ^2＝4．222、3.933,均P ＜0．05）。治疗后观察组和对照组患者外周血 CD4＋CD2＋5 FoxP3＋Treg 细胞计数比30．66％比24.10％、7．49％比5．15％,血清IL-2、IL-4以及IFN-γ血清含量（15．6±4．3） ng／mL比（10．3±3．1） ng／mL、（9．5±2．7）ng／mL比（13．9±3．4）ng／mL、（37．1±4．3）ng／mL比（31．2±4．9）ng／mL,较治疗前均有不等程度的升高,且观察组显著高于对照组（χ^2＝4．329、4．012、4．568、4．105,均P＜0．05）。结论 CD4＋CD2＋5调节性T细胞数量减少或功能缺陷可能参与了特发性血小板减少性紫癜的发病进程,参麦注射液可能能够通过该环节发挥治疗作用。     

IFN-γ对胆囊癌荷瘤小鼠IL-10和单核-巨噬细胞的影响

目的探讨IFN-γ对胆囊癌小鼠模型中肿瘤内IL-10和单核-巨噬细胞的影响。方法20只BALB／C裸鼠通过皮下接种人胆囊癌细胞株GBC—SD构建胆囊癌小鼠模型,按照随机数字表法分为IFN-γ组和对照组（每组各10只）。IFN．叮组小鼠在肿瘤内注剃、鼠重组IFN-γ 0．1mL（1×10^5kU／L,生理盐水溶解）,对照组注射同等剂量的生理盐水,通过ELISA法检测肿瘤中鼠源性IL-10的表达情况,通过免疫组织化学染色法计数CDl4’细胞（单核-巨噬细胞）、CD64^＋细胞（M1型巨噬细胞）和CD206’细胞（M2型巨噬细胞）,并以Student’st检验对所得数据进行分析。结果接种肿瘤细胞1周后,裸鼠皮下全部成瘤,固定于左前肢腋下。IFN-γ组存活9只,对照组存活7只。IFN-γ组裸鼠肿瘤质量为（518±138）mg,对照组为（669±128）mg;IFN．1组肿瘤体积为（456±172）mm。,对照组为（505±146）mm。,两组裸鼠肿瘤质量和体积比较,差异无统计学意义（t=2．240,1．503,P〉0．05）。IFN-γ组裸鼠肿瘤中鼠源性IL-10浓度为（58±16）μg／g,显著低于对照组的（102±45）“g／g,两组比较,差异有统计学意义（t=2．796,P〈0．05）。IFN-γ组中单核-巨噬细胞计数为814-16,显著高于对照组的50-e21;M1型巨噬细胞计数为66±12,显著高于对照组的94-4;M2型巨噬细胞计数为154-4,显著低于对照组的40±14,两组细胞计数比较,差异均有统计学意义（t=3．214,13．127,6．914,P〈0．05）。结论IFN-γ能够降低肿瘤微环境中的IL-10浓度。IFN-γ能够诱导单核-巨噬细胞浸润至胆囊癌细胞问质中,主要分化为M1型巨噬细胞。     

Protein kinase C isoforms in atherosclerosis: Pro- or anti-inflammatory?

Atherosclerosis is a pathologic condition caused by chronic inflammation in response to lipid deposition in the arterial wall. There are many known contributing factors such as long-term abnormal glucose levels, smoking, hypertension, and hyperlipidemia. Under the influence of such factors, immune and non-immune effectors cells are activated and participate during the progression of atherosclerosis. Protein kinase C (PKC) family isoforms are key players in the signal transduction pathways of cellular activation and have been associated with several aspects of the atherosclerotic vascular disease. This review article summarizes the current knowledge of PKC isoforms functions during atherogenesis, and addresses differential roles and disputable observations of PKC isoforms. Among PKC isoforms, both PKCβ and PKCδ are the most attractive and potential therapeutic targets. This commentary discusses in detail the outcomes and current status of clinical trials on PKCβ and PKCδ inhibitors in atherosclerosis-associated disorders like diabetes and myocardial infarction. The risk and benefit of these inhibitors for clinical purposes will be also discussed. This review summarizes what is already being done and what else needs to be done in further targeting PKC isoforms, especially PKCβ and PKCδ, for therapy of atherosclerosis and atherosclerosis-associated vasculopathies in the future.