抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.

https://www.who.int/respiratory/copd/GOLD_WR_06.pdf

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.

At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

/pdf/free-radicals-in-the-physiological-control-of-cell-function-g3w3iyr0ph.pdf

Free Radicals in the Physiological Control of Cell Function

The REDCap consortium: Building an international community of software platform partners.

Comprehensive Integration of Single-Cell Data.

The circadian clock in animals and humans plays crucial roles in multiple physiological processes. Disruption of circadian homeostasis causes detrimental effects. Here, it is demonstrated that the disruption of the circadian rhythm by genetic deletion of mouse brain and muscle ARNT-like 1 (Bmal1) gene, coding for the key clock transcription factor, augments an exacerbated fibrotic phenotype in various tumors. Accretion of cancer-associated fibroblasts (CAFs), especially the alpha smooth muscle actin positive myoCAFs, accelerates tumor growth rates and metastatic potentials. Mechanistically, deletion of Bmal1 abrogates expression of its transcriptionally targeted plasminogen activator inhibitor-1 (PAI-1). Consequently, decreased levels of PAI-1 in the tumor microenvironment instigate plasmin activation through upregulation of tissue plasminogen activator and urokinase plasminogen activator. The activated plasmin converts latent TGF-β into its activated form, which potently induces tumor fibrosis and the transition of CAFs into myoCAFs, the latter promoting cancer metastasis. Pharmacological inhibition of the TGF-β signaling largely ablates the metastatic potentials of colorectal cancer, pancreatic ductal adenocarcinoma, and hepatocellular carcinoma. Together, these data provide novel mechanistic insights into disruption of the circadian clock in tumor growth and metastasis. It is reasonably speculated that normalization of the circadian rhythm in patients provides a novel paradigm for cancer therapy.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202301505

Disruption of the Clock Component Bmal1 in Mice Promotes Cancer Metastasis through the PAI-1-TGF-β-myoCAF-Dependent Mechanism.

NSAIDs and cardiovascular risk—Reply

Arachidonic acid is converted enzymatically into different prostaglandins (PG) by the activity of a key enzyme, PG-endoperoxide synthase (PGHS), which exhibits both bisoxygenase and peroxidase activity (1). Cell-specific isomerization or reduction of PGH2 by various synthases (isomerases) or reductases leads to the formation of different prostanoids (2). It has been demonstrated that mammalian cells contain two isoforms of PGHS referred to as PGHS-1 and PGHS-2, encoded by separated genes (3). PGHS-1 is constitutively expressed in most tissue including platelets, endothelial cells and monocytes. However, it is recognized that expresion of PGHS-1 may be regualted. For example, androgens upregulate PGHS-1 in seminiferous tubules (4), as do cytokines in bone marrow derived mast cells (5). PGHS-2 expression is readily induced by serum, growth factors, cytokines in wide variety of cell types (6,7). Conventionally, this has implied the predominant importance of this isoform in regulating the inflammatory response. Data consistent with this view of the roles of the two enzymes have been obtained from “knock out” mice (8–10). Thus, while the PGHS-1 knock out exhibits a normal phenotype (8), inflammatory responses were modified following disruption of the PGHS-2 gene (9).

PGHS-2 Dependent Formation of 8-Epi PGF2α by Human Monocytes

The invention is drawn to a new class of isoeicosanoids that have been identified as products of the oxidation of docosahexaenoic acid (DHA). The invention provides compositions and methods related to the new class of molecules.

Neurofurans-indices of oxidant stress

Abstract:Arising from the release of Irish and British state papers for the years 1974 and 1975, Professor Ronan Fanning wrote in the Irish Independent about the Irish government's reactions in 1975 to what appeared to be a danger that the British government might withdraw from Northern Ireland. This current article outlines the circumstances in which, as Minister for Foreign Affairs, I submitted a memorandum to government on this issue on 11 June 1975, incorporating a document prepared at the request of the government by the Inter-Departmental Unit on Northern Ireland. It also deals with the reactions of Conor Cruise O'Brien, Minister for Posts and Telegraphs and Labour Spokesman on Northern Ireland, and of Assistant Cabinet Secretary Dermot Nally to this memorandum, including their concern at any consultation with the SDLP on this issue; and it places this matter in the political context of the period.

Garret A. FitzGerald

Papers

Disruption of the Clock Component Bmal1 in Mice Promotes Cancer Metastasis through the PAI-1-TGF-β-myoCAF-Dependent Mechanism.

NSAIDs and cardiovascular risk—Reply

PGHS-2 Dependent Formation of 8-Epi PGF2α by Human Monocytes

Neurofurans-indices of oxidant stress

The 1974-5 Threat of a British Withdrawal from Northern Ireland