scholarly journals The biochemical basis of disease

2018 ◽  
Vol 62 (5) ◽  
pp. 619-642 ◽  
Author(s):  
Alastair J. Barr
Keyword(s):  
Liver Disease ◽  
Global Health ◽  
Cell Biology ◽  
Biochemical Basis ◽  
New Developments ◽  
Biochemical Pathways ◽  
Causes Of Disease ◽  
Health And Disease ◽  
Insight Into

This article gives the reader an insight into the role of biochemistry in some of the current global health and disease problems. It surveys the biochemical causes of disease in an accessible and succinct form while also bringing in aspects of pharmacology, cell biology, pathology and physiology which are closely aligned with biochemistry. The discussion of the selected diseases highlights exciting new developments and illuminates key biochemical pathways and commonalities. The article includes coverage of diabetes, atherosclerosis, cancer, microorganisms and disease, nutrition, liver disease and Alzheimer’s disease, but does not attempt to be comprehensive in its coverage of disease, since this is beyond its remit and scope. Consequently there are many fascinating biochemical aspects of diseases, both common and rare, that are not addressed here that can be explored in the further reading cited. Techniques and biochemical procedures for studying disease are not covered in detail here, but these can be found readily in a range of biochemical methods sources.

scholarly journals Role of Biological Sex in the Cardiovascular-Gut Microbiome Axis

2022 ◽  
Vol 8 ◽  
Author(s):  
Shuangyue Li ◽  
Georgios Kararigas
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Microbial Composition ◽  
Biological Sex ◽  
Technological Advances ◽  
Host Health ◽  
Health And Disease ◽  
And Function ◽  
Insight Into

There has been a recent, unprecedented interest in the role of gut microbiota in host health and disease. Technological advances have dramatically expanded our knowledge of the gut microbiome. Increasing evidence has indicated a strong link between gut microbiota and the development of cardiovascular diseases (CVD). In the present article, we discuss the contribution of gut microbiota in the development and progression of CVD. We further discuss how the gut microbiome may differ between the sexes and how it may be influenced by sex hormones. We put forward that regulation of microbial composition and function by sex might lead to sex-biased disease susceptibility, thereby offering a mechanistic insight into sex differences in CVD. A better understanding of this could identify novel targets, ultimately contributing to the development of innovative preventive, diagnostic and therapeutic strategies for men and women.

scholarly journals GlcNAcstatins are nanomolar inhibitors of human O-GlcNAcase inducing cellular hyper-O-GlcNAcylation

2009 ◽  
Vol 420 (2) ◽  
pp. 221-227 ◽  
Author(s):  
Helge C. Dorfmueller ◽  
Vladimir S. Borodkin ◽  
Marianne Schimpl ◽  
Daan M. F. van Aalten
Keyword(s):  
Active Site ◽  
Cell Biology ◽  
Rational Design ◽  
Catalytic Mechanism ◽  
Conserved Residues ◽  
Cellular Processes ◽  
Acetyl Group ◽  
Nanomolar Range ◽  
Insight Into

O-GlcNAcylation is an essential, dynamic and inducible post-translational glycosylation of cytosolic proteins in metazoa and can show interplay with protein phosphorylation. Inhibition of OGA (O-GlcNAcase), the enzyme that removes O-GlcNAc from O-GlcNAcylated proteins, is a useful strategy to probe the role of this modification in a range of cellular processes. In the present study, we report the rational design and evaluation of GlcNAcstatins, a family of potent, competitive and selective inhibitors of human OGA. Kinetic experiments with recombinant human OGA reveal that the GlcNAcstatins are the most potent human OGA inhibitors reported to date, inhibiting the enzyme in the sub-nanomolar to nanomolar range. Modification of the GlcNAcstatin N-acetyl group leads to up to 160-fold selectivity against the human lysosomal hexosaminidases which employ a similar substrate-assisted catalytic mechanism. Mutagenesis studies in a bacterial OGA, guided by the structure of a GlcNAcstatin complex, provides insight into the role of conserved residues in the human OGA active site. GlcNAcstatins are cell-permeant and, at low nanomolar concentrations, effectively modulate intracellular O-GlcNAc levels through inhibition of OGA, in a range of human cell lines. Thus these compounds are potent selective tools to study the cell biology of O-GlcNAc.

Multifaceted MRGPRX2: New Insight into the Role of Mast Cells in Health and Disease

2021 ◽  
Author(s):  
Saptarshi Roy ◽  
Chalatip Chompunud Na Ayudhya ◽  
Monica Thapaliya ◽  
Vishwa Deepak ◽  
Hydar Ali
Keyword(s):  
Mast Cells ◽  
Health And Disease ◽  
Insight Into

Role of Toll-like receptors in liver health and disease

2011 ◽  
Vol 121 (10) ◽  
pp. 415-426 ◽  
Author(s):  
Ruth Broering ◽  
Mengji Lu ◽  
Joerg F. Schlaak
Keyword(s):  
Immune System ◽  
Liver Disease ◽  
Innate Immune System ◽  
Innate Immune ◽  
Toll Like Receptors ◽  
Evolutionarily Conserved ◽  
Liver Health ◽  
Health And Disease ◽  
Molecular Patterns

TLRs (Toll-like receptors), as evolutionarily conserved germline-encoded pattern recognition receptors, have a crucial role in early host defence by recognizing so-called PAMPs (pathogen-associated molecular patterns) and may serve as an important link between innate and adaptive immunity. In the liver, TLRs play an important role in the wound healing and regeneration processes, but they are also involved in the pathogenesis and progression of various inflammatory liver diseases, including autoimmune liver disease, alcoholic liver disease, non-alcoholic steatohepatitis, fibrogenesis, and chronic HBV (hepatitis B virus) and HCV (hepatitis C virus) infection. Hepatitis viruses have developed different evading strategies to subvert the innate immune system. Thus recent studies have suggested that TLR-based therapies may represent a promising approach in the treatment in viral hepatitis. The present review focuses on the role of the local innate immune system, and TLRs in particular, in the liver.

scholarly journals TASK-1 (KCNK3) channels in the lung: from cell biology to clinical implications

2017 ◽  
Vol 50 (5) ◽  
pp. 1700754 ◽  
Author(s):  
Andrea Olschewski ◽  
Emma L. Veale ◽  
Bence M. Nagy ◽  
Chandran Nagaraj ◽  
Grazyna Kwapiszewska ◽  
...  
Keyword(s):  
Pulmonary Circulation ◽  
Cell Biology ◽  
Unsaturated Fatty Acids ◽  
Excitable Cells ◽  
Intracellular Signalling Pathways ◽  
Current State ◽  
Health And Disease ◽  
Pulmonary Arterial ◽  
Pore Domain

TWIK-related acid-sensitive potassium channel 1 (TASK-1 encoded by KCNK3) belongs to the family of two-pore domain potassium channels. This gene subfamily is constitutively active at physiological resting membrane potentials in excitable cells, including smooth muscle cells, and has been particularly linked to the human pulmonary circulation. TASK-1 channels are sensitive to a wide array of physiological and pharmacological mediators that affect their activity such as unsaturated fatty acids, extracellular pH, hypoxia, anaesthetics and intracellular signalling pathways. Recent studies show that modulation of TASK-1 channels, either directly or indirectly by targeting their regulatory mechanisms, has the potential to control pulmonary arterial tone in humans. Furthermore, mutations in KCNK3 have been identified as a rare cause of both familial and idiopathic pulmonary arterial hypertension. This review summarises our current state of knowledge of the functional role of TASK-1 channels in the pulmonary circulation in health and disease, with special emphasis on current advancements in the field.

scholarly journals Fibrogénesis hepática células estelares hepáticas

Tequio ◽  
2018 ◽  
Vol 1 (2) ◽  
pp. 79-84
Author(s):  
Osiris G Ildefonso García ◽  
Alma Aurora Ramírez Hernández ◽  
Jovito César Santos Álvarez ◽  
Juan M Velázquez Enriquez ◽  
Gabriel Carrasco Torres ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
Biliary Disease ◽  
Considerable Evidence ◽  
Insight Into

Liver fibrosis affects both the amount and the composition of the extracellular matrix. This process may occur during chronic liver disease characterized by hepato biliary disease or inflammation. There is now considerable evidence to support the role of the hepatic stellar cells (HSC) as the main matrix producing cells in fibrogenesis. The focus of this review is to provide insight into hepatic stellar cells in the fibrogenic process.

A causal concept Of disease in an Iranian community

1978 ◽  
Vol 10 (4) ◽  
pp. 347-351
Author(s):  
Ali A. Alemi ◽  
Manouchehr Mohseni
Keyword(s):  
Rural Areas ◽  
Concept Of Disease ◽  
Old People ◽  
Traditional Beliefs ◽  
Cultural Variables ◽  
Evil Eye ◽  
Causes Of Disease ◽  
Health And Disease ◽  
Causal Concept

SummaryIn 1975, as part of a socio-medical survey in a southern province of Iran, the influence of socio-cultural variables on behaviour in relation to illness and on beliefs about the causes of disease was examined. It was found that traditional beliefs such as ‘luck’ and religion were related to locality and age. For instance, the urban literate community puts less emphasis than the illiterate rural population on such beliefs. Older people and those living in rural areas still tend to believe in as ‘evil eye’ as a cause of disease, but a small percentage of old people in both localities do believe that flies can cause disease. The causal role of culture or specific elements of culture on health and disease requires further study.

scholarly journals MicroRNA Signature in Alcoholic Liver Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Shashi Bala ◽  
Gyongyi Szabo
Keyword(s):  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Current Knowledge ◽  
Isolated Hepatocytes ◽  
Tnf Alpha ◽  
Insight Into ◽  
Global Health Problem

Alcoholic liver disease (ALD) is a major global health problem. Chronic alcohol use results in inflammation and fatty liver, and in some cases, it leads to fibrosis and cirrhosis or hepatocellular carcinoma. Increased proinflammatory cytokines, particularly TNF alpha, play a central role in the pathogenesis of ALD. TNF alpha is tightly regulated at transcriptional and posttranscriptional levels. Recently, microRNAs (miRNAs) have been shown to modulate gene functions. The role of miRNAs in ALD is getting attention, and recent studies suggest that alcohol modulates miRNAs. Recently, we showed that alcohol induces miR-155 expression both in vitro (RAW 264.7 macrophage) and in vivo (Kupffer cells, KCs of alcohol-fed mice). Induction of miR-155 contributed to increased TNF alpha production and to the sensitization of KCs to produce more TNF alpha in response to LPS. In this paper, we summarize the current knowledge of miRNAs in ALD and also report increased expression of miR-155 and miR-132 in the total liver as well as in isolated hepatocytes and KCs of alcohol-fed mice. Our novel finding of the alcohol-induced increase of miRNAs in hepatocytes and KCs after alcohol feeding provides further insight into the evolving knowledge regarding the role of miRNAs in ALD.

scholarly journals Peroxisomal Hydrogen Peroxide Metabolism and Signaling in Health and Disease

2019 ◽  
Vol 20 (15) ◽  
pp. 3673 ◽  
Author(s):  
Lismont ◽  
Revenco ◽  
Fransen
Keyword(s):  
Hydrogen Peroxide ◽  
Molecular Mechanisms ◽  
Signaling Network ◽  
H2o2 Production ◽  
Peroxisomal Enzyme ◽  
Pathological Conditions ◽  
Health And Disease ◽  
Precise Role ◽  
Insight Into

Hydrogen peroxide (H2O2), a non-radical reactive oxygen species generated during many (patho)physiological conditions, is currently universally recognized as an important mediator of redox-regulated processes. Depending on its spatiotemporal accumulation profile, this molecule may act as a signaling messenger or cause oxidative damage. The focus of this review is to comprehensively evaluate the evidence that peroxisomes, organelles best known for their role in cellular lipid metabolism, also serve as hubs in the H2O2 signaling network. We first briefly introduce the basic concepts of how H2O2 can drive cellular signaling events. Next, we outline the peroxisomal enzyme systems involved in H2O2 metabolism in mammals and reflect on how this oxidant can permeate across the organellar membrane. In addition, we provide an up-to-date overview of molecular targets and biological processes that can be affected by changes in peroxisomal H2O2 metabolism. Where possible, emphasis is placed on the molecular mechanisms and factors involved. From the data presented, it is clear that there are still numerous gaps in our knowledge. Therefore, gaining more insight into how peroxisomes are integrated in the cellular H2O2 signaling network is of key importance to unravel the precise role of peroxisomal H2O2 production and scavenging in normal and pathological conditions.

Early-Phase Alcoholic Liver Disease: An Update on Animal Models, Pathology, and Pathogenesis

2004 ◽  
Vol 23 (4) ◽  
pp. 217-231 ◽  
Author(s):  
Shashi K. Ramaiah ◽  
Chantal Rivera ◽  
Gavin E. Arteel
Keyword(s):  
Liver Disease ◽  
Animal Models ◽  
Alcoholic Liver Disease ◽  
Early Phase ◽  
Morbidity And Mortality ◽  
Alcohol Metabolism ◽  
Pathologic Findings ◽  
Common Etiology ◽  
Insight Into

Alcoholic liver disease (ALD) remains to be one of the most common etiology of liver disease and is a major cause of morbidity and mortality worldwide. The pathologic stages of ALD comprises of steatosis, steatohepatitis, and fibrosis/cirrhosis. Steatosis and steatohepatitis represents the early phase of ALD and are precursor stages for fibrosis/cirrhosis. Numerous research efforts have been directed at recognizing cofactors interacting with alcohol in the pathogenesis of steatosis and steatohepatitis. This review will elucidate the constellation of complex pathogenesis, available animal models, and microscopic pathologic findings mostly in the early-phase of ALD. The role of endotoxin, reactive oxygen species, alcohol metabolism, and cytokines are discussed. Understanding the mechanisms of early-phase ALD should provide insight into the development of therapeutic strategies and thereby decrease the morbidity and mortality associated with ALD.

Sign in / Sign up

Export Citation Format

Share Document