外泌体在力相关牙周炎症反应中的作用

外泌体是细胞分泌的含有多种分子成分的细胞外囊泡,可以通过自分泌和旁分泌作用来发挥细胞间物质运 输和信号交流的功能。 外泌体在体内存在广泛,参与多种生理、病理过程,包括与力相关的炎症反应。 牙周组织中 存在着力学刺激感受细胞,可以感受牙齿受到的应力。 其中,适量的力学载荷可以维持牙周组织的健康,而过度的 力学载荷则可能引起牙周组织的破坏和吸收,导致牙周组织发生炎症反应。 本文对外泌体在力相关的炎症反应, 尤其是牙周组织炎症反应中的作用进行综述。     

成骨细胞的体外剪切应力加载实验的变形分析及信号转导区域探讨

目的 根据已有体外培养鼠成骨细胞的参数实验数据,估算剪切应力加载实验中细胞整体剪切形变,借以研究细胞的主要转导区域.方法 计算过程采用黏弹性力学理论,对细胞运用了标准黏弹性模型,并简化其膜所受剪切力为均匀.结果 细胞剪切力产生的细胞变形大约是引起成骨细胞相同生物学响应的拉伸加载变形的十分之一.结论 从细胞总的力学刺激生物学响应来看,剪切应力加载实验中细胞的整体变形所产生的力学转导是可以忽略的,主要转导区域在承受剪切应力的细胞膜.     

细胞力学2022年度研究进展

细胞的力学微环境在调控其生理功能方面起关键作用。体内细胞经常受到剪切、拉伸、压缩等多种力学载荷,并且可以通过黏附分子(如整合素-配体素的结合)连接到细胞外基质上,进而可以感知外基质的硬度。细胞力学主要研究活细胞在力学载荷下的力学特性和行为,以及这些特征和行为与细胞功能的关系。本文综述2022年度细胞力学领域的研究进展,主要关注整合素-配体素间的相互作用,以及外基质硬度和力学载荷对细胞生理行为和形态发生的影响。     

细胞力学2021年度研究进展

细胞处于复杂的生理力学和物理环境中,前者包括剪切、拉伸、压缩、扭转等,后者则涵盖细胞外基质硬度与拓扑、空间限位、体积受限、渗透压力等,呈现多方式、多模态和多参数的特点。细胞力学重点关注细胞力学性质变化及其亚细胞组元的力学重建,不同力学和物理环境下细胞发育、生长、增殖、分化和凋亡的动力学过程,细胞对作用力的感知、传递、传导和响应机制及其与周围环境的相互作用等。本文综述了2021年度细胞力学研究在心血管、骨、免疫、肿瘤、干细胞等方面的主要进展,并涵盖了相关新技术的发展。     

缓冲型圆锥型套筒冠的位移与应力分析

采用有限元法对缓冲型圆锥型套筒冠固位体的缓冲间隙与义齿支持组织位移与应力分布进行研究，结果表明，加载力在１３０Ｎ前义齿支持组织中基托下组织应力值明显大于牙周组织，当加载达１３０Ｎ后，固位体内外冠面间隙消失，基牙牙周支持组织应力明显增加，义齿的二种支持组织应力差值减少。     

离体培养细胞的力学实验方法

细胞力学是组织工程和细胞工程的基础之一，在细胞离体培养过程中对细胞施加不同的机械力以研究应力对细胞的影响是细胞力学的一个重要研究领域， 也是细胞力学的重要研究手段。本文综述了离体培养细胞的力学实验方法，根据不同的载荷施加方式可分为：微吸管吸吮技术、压力载荷法、基底拉伸法和流体剪切法等，并指出了各种方法存在的利与弊。     

骨细胞的力学感受器

骨细胞是骨骼中最丰富和寿命最长的细胞,是骨重建的调节器。骨细胞在内分泌调节和钙磷酸盐代谢中发挥重要作用,也是力学刺激的主要响应者,感知力学刺激以直接或间接的方式对刺激做出反应。骨细胞中的力学转导是一个复杂而精细的调节过程,涉及细胞与其周围环境、相邻细胞以及细胞内部不同功能的力学感受器之间的相互作用。目前已知的骨细胞主要力学感受器包括初级纤毛、Piezo离子通道、整合素、细胞外基质以及基于连接蛋白的细胞间连接。这些力学感受器在骨细胞中发挥着至关重要的作用,它们能够感知并转导力学信号,进而调节骨稳态。本文对5种力学感受器进行系统的介绍,以期为理解骨细胞如何响应力学刺激和维持骨组织稳态提供新的视角和认识。     

细胞核力学生物学及其调控机制的研究进展EI北大核心

细胞核作为细胞内重要的遗传与调控中心,不但是细胞内生化信号的终端效应器,还能在细胞感知并应答力学刺激后,通过直接或间接的核力学信号调节对细胞的功能与表型产生重要影响。细胞核依靠染色质—核膜—细胞骨架等基础结构将其与其他胞内、外的物理微环境耦合,响应力学刺激并做出应答。该力学响应级联中,细胞核形态结构的变化是最直观的表现,也是细胞核直接响应力学刺激的基础。基于此类细胞核与细胞行为、表型的联系,核的异常形态变化被作为疾病诊断工具广泛用于临床实践。本文回顾了细胞核形变如何响应和适应力学刺激的证据,并着重综述了细胞核形变的力学调控因素,以及核形变涉及到的包括肿瘤在内的生理病理过程及其力学调控机制和研究进展,为深入理解细胞核力学参与的疾病发展调控机制和作为潜在靶点用于诊疗提供新的思路。     

体外细胞培养的加力装置及压力测量的研究

目的：在一定力学作用下,机体的器官、组织、细胞和生物大分子会发生相应的形态和功能改变,这对于维持正常生理功能具有重要作用。细胞力学是组织工程和细胞工程的基础之一,在离体培养过程中对细胞施加不同的机械力以研究应力对细胞的影响是细胞力学的一个重要研究领域,也是细胞力学的重要研究手段。本研究是为了模拟在体细胞的力学环境,实现在体外培养的条件下对细胞施加力的作用,设计了一种力加载装置和相应的压力检测模块。方法：力加载装置包括应力加载模块、细胞培养室、步进电机传动模块组成。计算机通过软件驱动步进电机控制活塞在培养室内直线往复运动,实现细胞培养室内压力大小、频率和持续时间的可控变化。应力检测模块可以实时监测培养室内压力大小的变化,并与预期参数对比后通过反馈系统调节各模块的运行,实现压力加载的精准控制。结果：系统压力加载的频率调控范围为0 Hz~1Hz,压力加载范围为-71 kPa~60 kPa。结论：该系统为研究压力对细胞的影响提供了一种简单、可行的方法,实验证明系统压力加载方式准确、可行,能对离体培养的细胞进行有效的压力加载。     

雌激素受体在骨生长、代谢及其力学响应中的作用和机制

力学信号在骨组织的生长、重建和疾病治疗中发挥着重要的作用。近年来的研究发现雌激素受体(estrogenreceptor,ER)能介导雌激素效应调节骨组织细胞的增殖、凋亡以及功能活性,从而影响骨形成和骨吸收,在骨组织生长、骨重建中发挥重要作用;同时参与骨组织及其细胞对力学刺激的响应过程。骨组织响应力学刺激的效应要受到ER数量和(或)功能活性的影响。这些研究提示了力学刺激和雌激素可能通过一些共同的信号通路来调节骨组织细胞的功能活性。本文着重关注ER在骨组织及其力学响应中的作用和机制。     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

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 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.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

'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.     

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.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.