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Cell Reports Jun 2023Reelin was originally identified as a regulator of neuronal migration and synaptic function, but its non-neuronal functions have received far less attention. Reelin... (Review)
Review
Reelin was originally identified as a regulator of neuronal migration and synaptic function, but its non-neuronal functions have received far less attention. Reelin participates in organ development and physiological functions in various tissues, but it is also dysregulated in some diseases. In the cardiovascular system, Reelin is abundant in the blood, where it contributes to platelet adhesion and coagulation, as well as vascular adhesion and permeability of leukocytes. It is a pro-inflammatory and pro-thrombotic factor with important implications for autoinflammatory and autoimmune diseases such as multiple sclerosis, Alzheimer's disease, arthritis, atherosclerosis, or cancer. Mechanistically, Reelin is a large secreted glycoprotein that binds to several membrane receptors, including ApoER2, VLDLR, integrins, and ephrins. Reelin signaling depends on the cell type but mostly involves phosphorylation of NF-κB, PI3K, AKT, or JAK/STAT. This review focuses on non-neuronal functions and the therapeutic potential of Reelin, while highlighting secretion, signaling, and functional similarities between cell types.
Topics: Humans; Brain; Cell Adhesion Molecules, Neuronal; Extracellular Matrix Proteins; Inflammation; LDL-Receptor Related Proteins; Nerve Tissue Proteins; Receptors, LDL; Serine Endopeptidases; Reelin Protein
PubMed: 37339050
DOI: 10.1016/j.celrep.2023.112669 -
Deutsches Arzteblatt International Nov 2023The prevalence of inflammatory bowel disease (IBD) is rising globally. In Germany, these conditions affect 0.7% of the population, or approximately 600 000 patients.... (Review)
Review
BACKGROUND
The prevalence of inflammatory bowel disease (IBD) is rising globally. In Germany, these conditions affect 0.7% of the population, or approximately 600 000 patients. Treatment strategies have become more diversified as a result of an improved understanding of disease pathogenesis. It remains unclear how the currently available drugs should best be used in each individual patient.
METHODS
This review is based on pertinent publications retrieved by a selective search in PubMed, with special attention to phase III and IV trials and to the German and European guidelines on the treatment of IBD.
RESULTS
An improved understanding of the immunological mechanisms of disease underlies the current treatment strategies in patients with IBD. For those with a complex clinical course, monoclonal antibodies against pro-inflammatory cytokines (TNF, IL-12/IL-23, IL-23) and cell adhesion molecules (α4β7) are of established therapeutic value, along with "small molecules" such as JAK inhibitors and sphingosine-1-phosphate receptor modulators. The numerous studies that have been performed, only a few of which have been head-to-head comparison trials, and the (network) meta-analyses that have been published to date do not imply that any single one of these drugs can be considered the universal, primary treatment for all patients with IBD. In this review, we discuss the available substances and certain important differential-therapeutic aspects of the treatment of IBD.
CONCLUSION
The treatment of a patient with IBD must take his or her prior treatment(s) and comorbidities into account, along with individual patient characteristics and treatment goals. Rational decision-making is required on the basis of the mechanism of action and the side-effect profile of the various drugs that are now available for use.
Topics: Humans; Male; Female; Inflammatory Bowel Diseases; Antibodies, Monoclonal; Cytokines; Interleukin-23; Germany
PubMed: 37408514
DOI: 10.3238/arztebl.m2023.0142 -
The Lancet. Global Health Aug 2023Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and imposes a substantial economic burden. Gaining a thorough understanding of...
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and imposes a substantial economic burden. Gaining a thorough understanding of the economic implications of COPD is an important prerequisite for sound, evidence-based policy making. We aimed to estimate the macroeconomic burden of COPD for each country and establish its distribution across world regions.
METHODS
In this health-augmented macroeconomic modelling study we estimated the macroeconomic burden of COPD for 204 countries and territories over the period 2020-50. The model accounted for (1) the effect of COPD mortality and morbidity on labour supply, (2) age and sex specific differences in education and work experience among those affected by COPD, and (3) the impact of COPD treatment costs on physical capital accumulation. We obtained data from various public sources including the Global Burden of Disease Study 2019, the World Bank database, and the literature. The macroeconomic burden of COPD was assessed by comparing gross domestic product (GDP) between a scenario projecting disease prevalence based on current estimates and a counterfactual scenario with zero COPD prevalence from 2020 to 2050.
FINDINGS
Our findings suggest that COPD will cost the world economy INT$4·326 trillion (uncertainty interval 3·327-5·516; at constant 2017 prices) in 2020-50. This economic effect is equivalent to a yearly tax of 0·111% (0·085-0·141) on global GDP. China and the USA face the largest economic burdens from COPD, accounting for INT$1·363 trillion (uncertainty interval 1·034-1·801) and INT$1·037 trillion (0·868-1·175), respectively.
INTERPRETATION
The macroeconomic burden of COPD is large and unequally distributed across countries, world regions, and income levels. Our study stresses the urgent need to invest in global efforts to curb the health and economic burdens of COPD. Investments in effective interventions against COPD do not represent a burden but could instead provide substantial economic returns in the foreseeable future.
FUNDING
Alexander von Humboldt Foundation, National Natural Science Foundation of China, CAMS Innovation Fund for Medical Science, Chinese Academy of Engineering project, Chinese Academy of Medical Sciences and Peking Union Medical College project, and Horizon Europe.
TRANSLATIONS
For the Chinese and German translations of the abstract see Supplementary Materials section.
Topics: Male; Female; Humans; Financial Stress; Pulmonary Disease, Chronic Obstructive; Cost of Illness; Gross Domestic Product; China; Global Health
PubMed: 37474226
DOI: 10.1016/S2214-109X(23)00217-6 -
International Journal of Molecular... Sep 2023This Special Issue-dedicated to high-quality review papers in molecular microbiology-is highlighting two important developments in the field: (i) the analysis of...
This Special Issue-dedicated to high-quality review papers in molecular microbiology-is highlighting two important developments in the field: (i) the analysis of microbiome data in health and disease and (ii) the search for strategies against bacteria showing antimicrobial resistance [...].
Topics: Microbiota; Review Literature as Topic; Drug Resistance, Bacterial
PubMed: 37762293
DOI: 10.3390/ijms241813990 -
American Journal of Clinical Dermatology Jul 2023Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including... (Review)
Review
Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including infections, vaccinations, ingestion of various substances, and spider bites, have also been described. AGEP is characterized by the development of edema and erythema followed by the eruption of multiple punctate, non-follicular, sterile pustules and subsequent desquamation. AGEP typically has a rapid onset and prompt resolution within a few weeks. The differential diagnoses for AGEP are broad and include infectious, inflammatory, and drug-induced etiologies. Diagnosis of AGEP depends on both clinical and histologic criteria, as cases of overlap with other disease processes have been reported. Management includes removal of the offending drug or treatment of the underlying cause, if necessary, and supportive care, as AGEP is a self-limited disease. This review aims to provide an overview and update on the epidemiology, pathogenesis, reported precipitating factors, differentials, diagnosis, and management of AGEP.
Topics: Humans; Acute Generalized Exanthematous Pustulosis; Diagnosis, Differential; Skin; Exanthema; Erythema
PubMed: 37156992
DOI: 10.1007/s40257-023-00779-3