scholarly journals Presence of Malassezia Hyphae Is Correlated with Pathogenesis of Seborrheic Dermatitis

2022 ◽  
Author(s):  
Juanjuan Li ◽  
Yahui Feng ◽  
Chen Liu ◽  
Zhiya Yang ◽  
Sybren de Hoog ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Clinical Observation ◽  
Seborrheic Dermatitis ◽  
Pathogenic Factors ◽  
The Way

Our results support the proposal that the hyphal form of Malassezia could be one of the pathogenic factors that contribute to SD, which has been previously less well studied. This clinical observation paves the way for further investigations of the molecular mechanisms of Malassezia hyphal pathogenicity in SD.

Reaching the Threshold: A Multilayer Pathogenesis of Macrophage Activation Syndrome

2013 ◽  
Vol 40 (6) ◽  
pp. 761-767 ◽  
Author(s):  
Raffaele Strippoli ◽  
Ivan Caiello ◽  
Fabrizio De Benedetti
Keyword(s):  
Mouse Models ◽  
Inflammatory Cytokines ◽  
Genetic Background ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Molecular Mechanisms ◽  
Fatal Complication ◽  
Pathogenic Factors ◽  
Laboratory Features ◽  
Activation Syndrome

Macrophage activation syndrome (MAS) is a potentially fatal complication of rheumatic diseases. The condition is considered part of secondary hemophagocytic lymphohistiocytoses (HLH). There are similarities in genetic background, pathogenesis, and clinical and laboratory features with primary HLH (p-HLH). We describe findings in mouse models of secondary HLH, comparing them with models of p-HLH and the cellular and molecular mechanisms involved, and relate them to recent findings in patients with secondary HLH. A multilayer model is presented in which background inflammation, infections, and genetics all contribute in different proportions and in several ways. Once the “threshold” has been reached, inflammatory cytokines are the final effectors, independent of the interplay between different upstream pathogenic factors.

scholarly journals Comprehensive Analysis of Common Different Gene Expression Signatures in the Neutrophils of Sepsis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zhaojun Liu ◽  
Yang Chen ◽  
Tingting Pan ◽  
Jialin Liu ◽  
Rui Tian ◽  
...  
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
Clinical Samples ◽  
Central Component ◽  
Inflammatory Disorder ◽  
Rt Pcr ◽  
Hub Gene ◽  
Pathway Enrichment ◽  
Protein Protein Interaction ◽  
Pathogenic Factors

The central component of sepsis pathogenesis is inflammatory disorder, which is related to dysfunction of the immune system. However, the specific molecular mechanism of sepsis has not yet been fully elucidated. The aim of our study was to identify genes that are significantly changed during sepsis development, for the identification of potential pathogenic factors. Differentially expressed genes (DEGs) were identified in 88 control and 214 septic patient samples. Gene ontology (GO) and pathway enrichment analyses were performed using David. A protein-protein interaction (PPI) network was established using STRING and Cytoscape. Further validation was performed using real-time polymerase chain reaction (RT-PCR). We identified 37 common DEGs. GO and pathway enrichment indicated that enzymes and transcription factors accounted for a large proportion of DEGs; immune system and inflammation signaling demonstrated the most significant changes. Furthermore, eight hub genes were identified via PPI analysis. Interestingly, four of the top five upregulated and all downregulated DEGs were involved in immune and inflammation signaling. In addition, the most intensive hub gene AKT1 and the top DEGs in human clinical samples were validated using RT-PCR. This study explored the possible molecular mechanisms underpinning the inflammatory, immune, and PI3K/AKT pathways related to sepsis development.

scholarly journals New gadget in the membrane trafficking toolbox: A novel inhibitor of SNARE priming

2019 ◽  
Vol 294 (46) ◽  
pp. 17186-17187
Author(s):  
Hagai Abeliovich
Keyword(s):  
Small Molecule ◽  
Membrane Trafficking ◽  
Molecular Mechanisms ◽  
Reversible Inhibitors ◽  
Sensitive Factor ◽  
The Way

NSF (N-ethylmaleimide sensitive factor) and its yeast counterpart Sec18 are highly conserved homohexameric proteins that play vital roles in eukaryotic membrane trafficking. Sec18 functions by disrupting SNARE complexes formed in cis, on the same membrane. However, the molecular mechanisms of this process are poorly understood, in large part due to the lack of selective, reversible inhibitors. A new study by Sparks et al. now reports a small molecule that appears to selectively inhibit Sec18 action in an in vitro assay. Their finding now paves the way to elucidate further details of Sec18-mediated SNARE priming.

scholarly journals RNAInter in 2020: RNA interactome repository with increased coverage and annotation

2019 ◽  
Vol 48 (D1) ◽  
pp. D189-D197 ◽  
Author(s):  
Yunqing Lin ◽  
Tianyuan Liu ◽  
Tianyu Cui ◽  
Zhao Wang ◽  
Yuncong Zhang ◽  
...  
Keyword(s):  
Rna Editing ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Interaction Data ◽  
Biological Functions ◽  
Additional Species ◽  
Dynamic Expression ◽  
Regulatory Landscape ◽  
The Way

Abstract Research on RNA-associated interactions has exploded in recent years, and increasing numbers of studies are not limited to RNA–RNA and RNA–protein interactions but also include RNA–DNA/compound interactions. To facilitate the development of the interactome and promote understanding of the biological functions and molecular mechanisms of RNA, we updated RAID v2.0 to RNAInter (RNA Interactome Database), a repository for RNA-associated interactions that is freely accessible at http://www.rna-society.org/rnainter/ or http://www.rna-society.org/raid/. Compared to RAID v2.0, new features in RNAInter include (i) 8-fold more interaction data and 94 additional species; (ii) more definite annotations organized, including RNA editing/localization/modification/structure and homology interaction; (iii) advanced functions including fuzzy/batch search, interaction network and RNA dynamic expression and (iv) four embedded RNA interactome tools: RIscoper, IntaRNA, PRIdictor and DeepBind. Consequently, RNAInter contains >41 million RNA-associated interaction entries, involving more than 450 thousand unique molecules, including RNA, protein, DNA and compound. Overall, RNAInter provides a comprehensive RNA interactome resource for researchers and paves the way to investigate the regulatory landscape of cellular RNAs.

scholarly journals The Interrelation between Reactive Oxygen Species and Autophagy in Neurological Disorders

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Congcong Fang ◽  
Lijuan Gu ◽  
Daniel Smerin ◽  
Shanping Mao ◽  
Xiaoxing Xiong
Keyword(s):  
Cerebral Ischemia ◽  
Neurological Disorders ◽  
Molecular Mechanisms ◽  
Cell Damage ◽  
Cellular Defense ◽  
Neuronal Homeostasis ◽  
Pathogenic Factors ◽  
The Brain ◽  
Cytotoxic Substance

Neurological function deficits due to cerebral ischemia or neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) have long been considered a thorny issue in clinical treatment. Recovery after neurologic impairment is fairly limited, which poses a major threat to health and quality of life. Accumulating evidences support that ROS and autophagy are both implicated in the onset and development of neurological disorders. Notably, oxidative stress triggered by excess of ROS not only puts the brain in a vulnerable state but also enhances the virulence of other pathogenic factors, just like mitochondrial dysfunction, which is described as the culprit of nerve cell damage. Nevertheless, autophagy is proposed as a subtle cellular defense mode against destructive stimulus by timely removal of damaged and cytotoxic substance. Emerging evidence suggests that the interplay of ROS and autophagy may establish a determinant role in the modulation of neuronal homeostasis. However, the underlying regulatory mechanisms are still largely unexplored. This review sets out to afford an overview of the crosstalk between ROS and autophagy and discusses relevant molecular mechanisms in cerebral ischemia, AD, and PD, so as to provide new insights into promising therapeutic targets for the abovementioned neurological conditions.

Array lessons from the heart: focus on the genome and transcriptome of cardiomyopathies

2005 ◽  
Vol 21 (2) ◽  
pp. 131-143 ◽  
Author(s):  
Despina Sanoudou ◽  
Elizabeth Vafiadaki ◽  
Demetrios A. Arvanitis ◽  
Evangelia Kranias ◽  
Aikaterini Kontrogianni-Konstantopoulos
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Normal Function ◽  
Study Data ◽  
Cardiovascular Research ◽  
Single Experiment ◽  
New Era ◽  
Optimum Experimental Design ◽  
End Stage ◽  
The Way

Our understanding of the cardiovascular system has evolved through the years by extensive studies emphasizing the identification of the molecular and physiological mechanisms involved in its normal function and disease pathogenesis. Major discoveries have been made along the way. However, the majority of this work has focused on specific genes or pathways rather than integrative approaches. In cardiomyopathies alone, over 30 different loci have shown mutations with varying inheritance patterns, yet mostly coding for structural proteins. The emergence of microarrays in the early 1990s paved the way to a new era of cardiovascular research. Microarrays dramatically accelerated the rhythm of discoveries by giving us the ability to simultaneously study thousands of genes in a single experiment. In the field of cardiovascular research, microarrays are having a significant contribution, with the majority of work focusing on end-stage cardiomyopathies that lead to heart failure. Novel molecular mechanisms have been identified, known pathways are seen under new light, disease subgroups begin to emerge, and the effects of various drugs are molecularly dissected. This cross-study data comparison concludes that consistent energy metabolism gene expression changes occur across dilated, hypertrophic, and ischemic cardiomyopathies, while Ca2+ homeostasis changes are prominent in the first two cardiomyopathies, and structural gene expression changes accompany mostly the dilated form. Gene expression changes are further correlated to disease genetics. The future of microarrays in the cardiomyopathy field is discussed with an emphasis on optimum experimental design and on applications in diagnosis, prognosis, and drug discovery.

Reshaping biological membranes in endocytosis: crossing the configurational space of membrane-protein interactions

2014 ◽  
Vol 395 (3) ◽  
pp. 275-283 ◽  
Author(s):  
Mijo Simunovic ◽  
Patricia Bassereau
Keyword(s):  
Membrane Protein ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Full Range ◽  
Biological Membranes ◽  
Membrane Properties ◽  
Physical Parameters ◽  
Membrane Remodeling ◽  
Experimental Conditions ◽  
The Way

Abstract Lipid membranes are highly dynamic. Over several decades, physicists and biologists have uncovered a number of ways they can change the shape of membranes or alter their phase behavior. In cells, the intricate action of membrane proteins drives these processes. Considering the highly complex ways proteins interact with biological membranes, molecular mechanisms of membrane remodeling still remain unclear. When studying membrane remodeling phenomena, researchers often observe different results, leading them to disparate conclusions on the physiological course of such processes. Here we discuss how combining research methodologies and various experimental conditions contributes to the understanding of the entire phase space of membrane-protein interactions. Using the example of clathrin-mediated endocytosis we try to distinguish the question ‘how can proteins remodel the membrane?’ from ‘how do proteins remodel the membrane in the cell?’ In particular, we consider how altering physical parameters may affect the way membrane is remodeled. Uncovering the full range of physical conditions under which membrane phenomena take place is key in understanding the way cells take advantage of membrane properties in carrying out their vital tasks.

scholarly journals Integrating mechanisms of pulmonary fibrosis

2011 ◽  
Vol 208 (7) ◽  
pp. 1339-1350 ◽  
Author(s):  
Thomas A. Wynn
Keyword(s):  
Pulmonary Fibrosis ◽  
Molecular Mechanisms ◽  
Complex Disease ◽  
Pathological Process ◽  
Therapeutic Options ◽  
Pathogenic Mechanisms ◽  
The Way

Pulmonary fibrosis is a highly heterogeneous and lethal pathological process with limited therapeutic options. Although research on the pathogenesis of pulmonary fibrosis has frequently focused on the mechanisms that regulate the proliferation, activation, and differentiation of collagen-secreting myofibroblasts, recent studies have identified new pathogenic mechanisms that are critically involved in the initiation and progression of fibrosis in a variety of settings. A more detailed and integrated understanding of the cellular and molecular mechanisms of pulmonary fibrosis could help pave the way for effective therapeutics for this devastating and complex disease.

scholarly journals Discovery of lipotoxicity-sensitive transcription factors in non-alcoholic steatohepatitis

2021 ◽  
Author(s):  
Joaquín Pérez-Schindler ◽  
Elyzabeth Vargas-Fernández ◽  
Bettina Karrer-Cardel ◽  
Danilo Ritz ◽  
Alexander Schmidt ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Chromatin Accessibility ◽  
Alcoholic Fatty Liver ◽  
Mouse Hepatocyte ◽  
Alcoholic Steatohepatitis ◽  
Pathogenic Factors ◽  
Mouse Hepatocytes ◽  
Regulated Gene Expression

Non-alcoholic fatty liver disease is continuum of disorders among which non-alcoholic steatohepatitis (NASH) is particularly associated with a negative prognosis. Hepatocyte lipotoxicity is one of the main pathogenic factors of liver fibrosis and NASH. However, the molecular mechanisms regulating this process are poorly understood. Here, we integrated transcriptomic and chromatin accessibility analyses from human liver and mouse hepatocytes to identify lipotoxicity-sensitive transcription factors. We found that the transcription factors MAFK and TCF4 were activated in liver from NASH patients and by mouse hepatocyte lipotoxicity. Genetic deletion of these transcription factors protected hepatocytes against saturated fatty acid oversupply. Notably, MAFK- and TCF4-regulated gene expression linked to lipotoxicity closely correlated with transcriptional patters in fibrosis progression in NASH patients. Collectively, our findings uncovered novel molecular insights into lipotoxicity-induced NASH, revealing the relevance and therapeutic potential of MAFK and TCF4 in human disease.

scholarly journals Cognizance of Molecular Methods for the Generation of Mutagenic Phage Display Antibody Libraries for Affinity Maturation

2019 ◽  
Vol 20 (8) ◽  
pp. 1861 ◽  
Author(s):  
Chia Chiu Lim ◽  
Yee Siew Choong ◽  
Theam Soon Lim
Keyword(s):  
Phage Display ◽  
Molecular Mechanisms ◽  
Combinatorial Libraries ◽  
Affinity Maturation ◽  
Fine Tuning ◽  
Human Antibody ◽  
Molecular Approaches ◽  
The Way

Antibodies leverage on their unique architecture to bind with an array of antigens. The strength of interaction has a direct relation to the affinity of the antibodies towards the antigen. In vivo affinity maturation is performed through multiple rounds of somatic hypermutation and selection in the germinal centre. This unique process involves intricate sequence rearrangements at the gene level via molecular mechanisms. The emergence of in vitro display technologies, mainly phage display and recombinant DNA technology, has helped revolutionize the way antibody improvements are being carried out in the laboratory. The adaptation of molecular approaches in vitro to replicate the in vivo processes has allowed for improvements in the way recombinant antibodies are designed and tuned. Combinatorial libraries, consisting of a myriad of possible antibodies, are capable of replicating the diversity of the natural human antibody repertoire. The isolation of target-specific antibodies with specific affinity characteristics can also be accomplished through modification of stringent protocols. Despite the ability to screen and select for high-affinity binders, some ‘fine tuning’ may be required to enhance antibody binding in terms of its affinity. This review will provide a brief account of phage display technology used for antibody generation followed by a summary of different combinatorial library characteristics. The review will focus on available strategies, which include molecular approaches, next generation sequencing, and in silico approaches used for antibody affinity maturation in both therapeutic and diagnostic applications.

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