线粒体功能障碍在急性肾损伤向慢性肾脏疾病转变中的作用

急性肾损伤(AKI)是一种发病率较高的临床综合征,会使远期慢性肾脏病(CKD)的发病率明显上升,其机制目前尚不完全明确,可能包括细胞周期停滞、小管上皮周围毛细血管变少、炎性细胞浸润等。线粒体功能障碍在其中的作用主要包括导致了过度氧化应激、促进炎性反应的发生及进展、直接诱导肾小管细胞凋亡等。     

栀子苷减轻幼年哮喘小鼠气道炎性反应并下调TLR4/NF-κB活性

目的探讨栀子苷(Gen)对幼年哮喘小鼠气道炎性反应和平滑肌细胞(ASMCs)损伤的保护作用。方法将小鼠分为对照组、哮喘组(Ova)和Gen组(Ova+Gen,80 mg/kg)(每组n=10)。苏木精-伊红(HE)和阿辛兰-过碘酸雪夫(AB-PAS)染色观察肺组织病理变化(细胞浸润和杯状黏液细胞分泌);观察支气管肺泡灌洗液(BALF)中炎性反应细胞嗜酸粒细胞、中性粒细胞和巨噬细胞数目;ELISA检测BALF中TLR4及Th2型细胞因子IL-4,IL-5及IL-13表达。体外分离和培养ASMCs,分为对照组、哮喘组(Ova)、低剂量Gen组(20 mg/L)、中剂量Gen组(50 mg/L)和高剂量Gen组(100 mg/L)(每组n=8)。qRT-PCR和Western blot检测TLR4和NF-κB P65表达;四甲基偶氮唑蓝法(MTT)检测ASMCs增殖。结果体内实验发现,Gen可显著降低肺部细胞浸润和杯状黏液细胞分泌;减少炎性反应细胞增多(P0.01);降低TLR4和Th2型细胞因子表达(P0.01)。体外实验发现,Gen可抑制TLR4/NF-κB表达;抑制ASMCs增殖。结论 Gen可能通过抑制TLR4/NF-κB活化减轻幼年哮喘小鼠气道炎性反应和SMCs损伤。     

内质网应激与急性呼吸窘迫综合征的研究进展

急性呼吸窘迫综合征(ARDS)是呼吸科及重症医学科的重点、难点,因无明确有效的治疗方法而病死率极高。内质网应激(ERS)可介导炎性反应及细胞凋亡,是ARDS的重要发病机制;并且抑制ERS可改善ARDS结果。     

氧化三甲胺促进人主动脉血管内皮细胞炎性反应

目的研究氧化三甲胺(TMAO)对人主动脉内皮细胞和小鼠腹主动脉血管炎性反应的影响,以及探究其对炎性反应信号通路NF-κB激活的情况。方法将人主动脉内皮细胞分为对照组和TMAO组(用TMAO处理细胞);CCK-8法检测细胞生存率;实时荧光定量PCR检测细胞炎性反应因子mRNA表达;蛋白免疫印迹法检测p65蛋白表达及其入核情况;体内小鼠实验分为对照组和TMAO组,用腹腔注射TMAO处理小鼠;用实时荧光定量PCR检测炎性因子mRNA的表达。结果在TMAO 1 000、3 000、5 000μmol/L浓度下,细胞生存率降低(P0. 01); TMAO处理细胞和小鼠后,炎性反应因子mRNA表达明显提高(P0. 05);磷酸化p65以及p65蛋白入核明显增加(P0. 05)。结论 TMAO可能通过激活NF-κB信号通路,刺激人主动脉血管内皮细胞释放炎性反应因子,并可能通过此机制影响动脉粥样硬化的发生和发展。     

自噬与炎性反应之间分子联系的研究进展

自噬是机体重要的代谢过程,参与细胞的多种应激反应如炎性反应。自噬与炎性反应之间具有密切的分子联系。一方面,多种炎性反应介质可调控自噬发生及自噬基因的转录;另一方面,自噬通过多种方式可抑制机体过激的炎性反应。因此,机体的多种炎性反应疾病包括克罗恩病(CD)可能与自噬缺陷相关。     

没食子酸减轻香烟烟雾诱导的小鼠气道炎性反应

目的 研究没食子酸(GA)对香烟烟雾(CS)诱导的小鼠慢性阻塞性肺病(COPD)相关的肺部炎性反应的作用。方法 构建CS诱导的小鼠模型。分析支气管肺泡灌洗液中的炎性细胞的数量和促炎细胞因子的水平。相应试剂盒检测肺组织匀浆中活性氧(ROS)、谷胱甘肽(GSH)、丙二醛(MDA)和蛋白羰基的活性。Western blot分析IL-13/STAT6通路活性。结果 GA抑制SC诱导的炎性细胞浸润(中性粒细胞、淋巴细胞和巨噬细胞)和促炎细胞因子(IL-6、TNF-α和IL-1β)的水平。GA可以减轻暴露于CS的小鼠肺组织氧化还原失衡。结论 GA有效地减轻COPD模型小鼠肺部炎性反应和氧化应激。     

单核苷酸多态性和免疫细胞在糖尿病肾脏疾病中的研究进展

糖尿病肾脏疾病具有很明显的家族聚集性及种族差异,已经确定了一些与糖尿病肾脏疾病易感性有关的单核苷酸多态性(SNPs),尤其是吞噬和细胞运动性1基因(ELMO1)和氯化钠共转运蛋白基因(SLC12A3),与中国人群糖尿病肾脏疾病发展进展有关;同时炎性反应在糖尿病肾脏疾病的发生和发展中起着关键作用,其中细胞和2型固有淋巴细胞(ILC2)分泌炎性因子促进肾脏慢性炎性反应及纤维化。     

抵抗素与冠心病

人类抵抗素主要在单核细胞和巨噬细胞中表达,具有抵抗胰岛素的作用.然而,目前许多研究表明抵抗素与冠心病具有密切关系,一方面,急性心肌损伤通过斑块的破裂、炎性反应和应激等机制可刺激血浆抵抗素水平升高;另一方面,血浆抵抗素水平升高通过引起血管内皮细胞功能紊乱,诱导炎症反应和氧化应激,促进泡沫细胞的形成,促进血管平滑肌细胞增殖、迁移,促进血管内皮细胞增殖、迁移及毛细血管生成和促进冠状动脉钙化等机制导致冠心病.     

咪达唑仑通过 NLRP3 / caspase-1 途径改善脂多糖诱导 H9c2 心肌细胞损伤

目的研究咪达唑仑轮对于脂多糖 (lipopolysaccharide, LPS) 诱导的 H9c2 心肌细胞损伤的作用 及其分子生物学机制。方法比较经不同浓度、 不同时间的咪达唑仑和 LPS 刺激的 H9c2 细胞活力以确定 达唑仑最佳给药条件; 将 H9c2 心肌细胞分为对照组、 咪达唑仑组、 LPS 组和 LPS + 咪达唑仑组, 比较各组 细胞凋亡率、 线粒体膜电位变化情况、 氧化应激指标、 炎性因子水平和 NOD 样受体蛋白 3 (NOD-like receptor protein3, NLRP3) / 胱天蛋白酶 1 (caspase-1) 途径相关蛋白表达水平, 并用 NLRP3 激活剂尼日利亚 菌素验证咪达唑仑的作用。结果咪达唑仑可降低 LPS 介导的 H9c2 心肌细胞凋亡率, 减轻氧化应激和炎 性反应, 提高 NLRP3 / caspase-1 通路相关蛋白表达水平。结论咪达唑仑对 LPS 介导的 H9c2 心肌细胞损伤 具有保护作用, 其作用机制可能与抑制 NLRP3 / caspase-1 通路相关。     

异柠檬酸脱氢酶1对肝内胆管细胞癌中炎性反应的影响

目的研究肝内胆管细胞癌(ICC)中异柠檬酸脱氢酶1(IDH1) 132位点核苷酸突变与炎性反应的关系,探讨IDH1突变对ICC发生的影响。方法收集ICCs标本131例。采用Sanger法分析IDH1突变位点; HE观察ICC炎性反应发生情况。用Cre-LoxP系统,构建IDH1 R132H肠道组织特异性基因突变小鼠;分离小鼠肝脏内胆管,HE观察小鼠肝内胆管及胆道炎性反应情况。用突变型IDH1代谢产物2-羟基戊二酸(2-HG)对巨噬细胞系THP-1进行干预;收集培养液上清,ELISA检测上清中M1型巨噬细胞标志物肿瘤坏死因子(TNF-α)和M2型标志物白介素-10(IL-10)的浓度。结果 131例ICC标本中IDH1(R132H)突变率为15. 3%(20/131)。与IDH1野生型组相比,IDH1(R132H)突变组标本中炎细胞浸润明显增多(P0. 01);在肠道组织特异性突变小鼠模型中也得到一致结果(P0. 05)。2-HG能够诱导M2型巨噬细胞标志物IL-10表达增多(P0. 01),而M1型标志物TNF-α变化没有统计学意义。结论 IDH1突变能够诱发胆管发生炎性反应,并促进THP-1巨噬细胞系向M2型极化,为进一步明确IDH1突变与肝内胆管细胞癌发生的关系以及靶向治疗提供依据。     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

Hypo- und Hypermagnesämie aus kardiologischer Sicht

Zusammenfassung Eine Reihe pathologischer Zustände bedingen Magnesiummangel. Zustände mit Hypermagnesämie sind ebenfalls bekannt, doch wesentlich seltener. Für den Kardiologen beachtenswert ist, daß unter Therapie mit bestimmten Diuretica bei Herzinsuffizienz, bei Herzinfarkt, Kardiomyopathie, Digitalisintoxikation und bestimmten Herzrhythmusstörungen Hypomagnesämie beobachtet wurde. Leider kann in der klinischen Routine nur ein extracelluläres Magnesiumdefizit durch Serumbestimmungen gemessen werden; über Magnesiummangel einzelner Organe kann nichts ausgesagt werden. Hinweise für Magnesiummangel geben aber neben der Messung des Serumspiegels Anamnese, klinischer Befund, bestimmte EKG-Veränderungen wie auch evtl. Hypokalämie, ein Zustand, bei dem sich oft — besonders bei Aldosteronismus — parallele Veränderungen zeigten.Tierexperimente deuten darauf hin, daß infarktähnliche Läsionen unter Magnesiummangel entstehen, doch ob Herzinfarkt beim Menschen durch Magnesiummangel ausgelöst werden kann, ist noch ungeklärt. In Leichenherzen zeigte sich im Infarktgebiet neben Calciumakkumulation signifikanter Magnesiumverlust, wobei unklar blieb, ob sich Ursache oder Folge des Infarktes widerspiegelten. Falls ein ursächlicher Zusammenhang besteht, ist er im Myokardstoffwechsel selbst zu suchen, wie bei der Alkoholkardiomyopathie, wo myokardialer Magnesiummangel zumindest als pathogenetischer Teilfaktor anerkannt wird. Andererseits versucht man aber auch Beziehungen zwischen Atherosklerose, Blutgerinnung und Hypomagnesämie herzustellen, in der Meinung, daß Magnesiummangel auch über den coronaren Pathomechanismus des Herzinfarktes wirken könnte. Sicher scheint, daß gewisse EKG-Veränderungen und Herzrhythmusstörungen durch einen irritierten Magnesiumhaushalt bedingt sein können, da sie bei Gabe bzw. Entzug von Magnesium verschwinden. Daß Magnesiummangel die Glykosidtoleranz verringert, wird tierexperimentell bestätigt. Unter Hypomagnesämie bewirkt Acetylstrophanthidin eher und länger Rhythmusstörungen als ohne, außerdem lassen diese sich durch Magnesiumgaben eliminieren. Da in gewissen Fällen spontane und digitalisinduzierte Herzrythmusstörungen durch Magnesiuminjektionen beseitigt wurden, scheint Magnesium als Therapeuticum angebracht. Einsatz verschiedener Magnesiumsalze bei Angina pectoris, degenerativen Herzerkrankungen und Herzinsuffizienz ohne geprüften und offensichtlich gestörten Magnesiumhaushalt ist fragwürdig, weil keine eindeutigen klinischen Erfolgsbeweise vorliegen. Immerhin mag es aber larvierte, durch Serumbestimmungen nicht erfaßbare Mangelzustände geben. Allgemein erscheint es aus kardiologischer Sicht ratsam, den Magnesiumhaushalt zu überwachen und in entsprechenden Fällen auszugleichen, um möglichen Myokardläsionen oder fatalen Herzrhythmusstörungen entgegenzuwirken.     

Environmental risk factors and their role in the management of atopic dermatitis

Introduction: The etiology of atopic dermatitis (AD) is multifactorial with interaction between genetics, immune and environmental factors.

Areas covered: We review the role of prenatal exposures, irritants and pruritogens, pathogens, climate factors, including temperature, humidity, ultraviolet radiation, outdoor and indoor air pollutants, tobacco smoke exposure, water hardness, urban vs. rural living, diet, breastfeeding, probiotics and prebiotics on AD.

Expert commentary: The increased global prevalence of AD cannot be attributed to genetics alone, suggesting that evolving environmental exposures may trigger and/or flare disease in predisposed individuals. There is a complex interplay between different environmental factors, including individual use of personal care products and exposure to climate, pollution, food and other exogenous factors. Understanding these complex risk factors is crucial to developing targeted interventions to prevent the disease in millions. Moreover, patients require counseling on optimal regimens for minimization of exposure to irritants and pruritogens and other harmful exposures.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

HLA genes in Amerindians from Mexico San Vicente Tancuayalab Teenek/Huastecos

Huastecos or Teenek Amerindians are presently living at North East Mexico (San Luis Potosi State). They have probably one of the most ancient culture of Mexico and Central America together with Mayas and Olmec groups with which also show close relationships. Proximity to Atlantic Ocean/Mexican Gulf originated that Spaniards had very early contact with them at about 1519 CE or before. In the present paper we have aimed to study HLA gene profile which may be useful for HLA and disease epidemiology and transplant programs in Teeneks. HLA-DRB1*04:07, -DRB1*14:06 and -DRB1*04:11 have been found in high frequency like in other Amerindian groups. High frequency typical Amerindians HLA extended haplotypes have been found, such as A*02-B*35-DRB1*04:07-DQB1*03:02; A*68-B*39-DRB1*04:07-DQB1*03:02 and A*02-B*39-DRB1*04:07-DQB1*03:02; also new haplotypes have been described, like A*02-B*52-DRB1*04:11-DQB1*03:02, A*68-B*35-DRB1*14:02-DQB1*03:01 and A*68-B*40-DRB1*16:02-DQB1*03:01. Genetic proximity is observed not only to linguistically close Mayans, but also to Mazatecans, Mixtecans and Zapotecans, who speak an altogether different languages; it shows once more that genes and languages do not correlate. This population was greatly diminished after European contact between 1500 and 1600 years CE; in fact, North and South America First Inhabitants population was brought from 80 down to 8 million people because of diseases (i.e.: measles, smallpox or influenza), slavery and war.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.