The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Dec. 10, 2020

The human microbiota has a fundamental role in host physiology and pathology. Gut microbial alteration, also known as dysbiosis, is condition associated not only with gastrointestinal disorders but diseases affecting other distal organs. Recently it became evident that the intestinal bacteria can affect central nervous system (CNS) inflammation. tract are communicating through bidirectional network of signaling pathways called gut-brain axis, which consists multiple connections, including vagus nerve, immune system, bacterial metabolites products. During these dysregulated altered permeability blood-brain barrier (BBB) neuroinflammation. However, numerous mechanisms behind impact gut neuro-development -pathogenesis remain poorly understood. There several involved CNS homeostasis Among those, inflammasome pathway been linked to neuroinflammatory conditions such sclerosis, Alzheimer’s Parkinson’s diseases, anxiety depressive-like disorders. complex assembles upon cell activation due exposure microbes, danger signals, or stress lead production pro-inflammatory cytokines (interleukin-1β interleukin-18) pyroptosis. Evidences suggest there reciprocal influence brain. how this precisely working yet be discovered. Herein, we discuss status knowledge open questions field focusing on function products cells during healthy inflammatory conditions, neuropsychiatric In particular, focus innate mechanism certain microbes.

Language: Английский

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Diversity and versatility of p38 kinase signalling in health and disease

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 22(5), P. 346 - 366

Published: Jan. 27, 2021

Language: Английский

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Targeting IL-6 trans-signalling: past, present and future prospects

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(10), P. 666 - 681

Published: April 17, 2023

Language: Английский

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Recent advances in mass spectrometry based clinical proteomics: applications to cancer research

Clinical Proteomics, Journal Year: 2020, Volume and Issue: 17(1)

Published: May 24, 2020

Abstract Cancer biomarkers have transformed current practices in the oncology clinic. Continued discovery and validation are crucial for improving early diagnosis, risk stratification, monitoring patient response to treatment. Profiling of tumour genome transcriptome now established tools novel biomarkers, but alterations proteome expression more likely reflect changes pathophysiology. In past, clinical diagnostics strongly relied on antibody-based detection strategies, these methods carry certain limitations. Mass spectrometry (MS) is a powerful method that enables increasingly comprehensive insights into advance personalized medicine. this review, recent improvements MS-based proteomics highlighted with focus oncology. We will provide detailed overview clinically relevant samples types, as well as, consideration sample preparation methods, protein quantitation MS configurations, data analysis pipelines currently available researchers. Critical each step necessary address pressing questions cancer diagnosis prognosis. While majority studies clinically-relevant there growing demand rigorous biomarker validation. These high-throughput targeted assays multi-centre standardized protocols. Additionally, sensitivity opening door new classes tumour-specific proteoforms including post-translational modifications variants originating from genomic aberrations. Overlaying proteomic complement transcriptomic datasets forges field proteogenomics, which shows great potential improve our understanding biology. Overall, advancements not only solidify proteomics’ integral position research, also accelerate shift towards becoming regular component routine practice.

Language: Английский

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Non-Alcoholic Steatohepatitis: A Review of Its Mechanism, Models and Medical Treatments

Frontiers in Pharmacology, Journal Year: 2020, Volume and Issue: 11

Published: Dec. 3, 2020

Non-alcoholic steatohepatitis (NASH) develops from non-alcoholic fatty liver disease (NAFLD). Currently, around 25% of the population is estimated to have NAFLD, and NAFLD patients are NASH. NASH typically characterized by steatosis inflammation, fibrosis driven metabolic disruptions such as obesity, diabetes, dyslipidemia. with significant increased risk developing cirrhosis failure. second leading cause for transplant in United States. More importantly, hepatocellular carcinoma has also been highlighted recent studies. Patients may years before progressing into Although pathogenesis not completely understood, current “multiple-hits” hypothesis suggests that addition fat accumulation, elevated oxidative ER stress drive inflammation fibrosis. The development clinically relevant animal models pharmacological treatments hampered limited understanding mechanism a lack sensitive, non-invasive diagnostic tools. most pre-clinical divided three main groups which includes: genetic models, diet-induced, toxin + diet-induced models. dietary mimic natural course humans, often only induce mild injury. Many rapidly disruption serious injury, but without their own shortcomings. This review provides an overview evaluation currently existing update on available interventions managing well agents undergoing clinical trials treatment

Language: Английский

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Non‐alcoholic fatty liver disease: a review of epidemiology, risk factors, diagnosis and management

Internal Medicine Journal, Journal Year: 2019, Volume and Issue: 50(9), P. 1038 - 1047

Published: Nov. 24, 2019

Due to the rising prevalence of obesity and type II diabetes mellitus, non-alcoholic fatty liver disease is becoming leading cause chronic in Western world. In some patients, simple steatosis can result steatohepatitis which over time lead cirrhosis its associated sequelae, including hepatocellular carcinoma. Early identification management patients at risk with intensive dietary lifestyle modification are essential prevent development advanced complications. this review, we will discuss epidemiology disease, pathogenesis, diagnosis, surveillance strategies offset morbidity mortality as well non-liver-related

Language: Английский

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Role of Interleukin-6 in Vascular Health and Disease

Frontiers in Molecular Biosciences, Journal Year: 2021, Volume and Issue: 8

Published: March 14, 2021

IL-6 is usually described as a pleiotropic cytokine produced in response to tissue injury or infection. As pro-inflammatory cytokine, activates innate and adaptative immune responses. released the by leukocytes well stromal cells upon pattern recognition receptor activation. then recruits triggers B T cell response. Dysregulated activity associated with pathologies involving chronic inflammation autoimmunity, including atherosclerosis. However, also under beneficial conditions, such exercise, where anti-inflammatory metabolic effects coupled physical adaptation intense training. Exercise-associated acts on adipose induce lipogenesis arteries vascular remodeling. These divergent actions could be explained complex signaling networks. Classical involves membrane-bound glycoprotein 130 (gp130), while trans-signaling relies soluble version of IL-6R (sIL-6R) gp130. Trans-signaling, but not classical pathway, regulated In this review, we discuss similarities differences myokine explain differential opposite protein during special focus system.

Language: Английский

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Patient‐derived xenograft model in cancer: establishment and applications

MedComm, Journal Year: 2025, Volume and Issue: 6(2)

Published: Jan. 19, 2025

Abstract The patient‐derived xenograft (PDX) model is a crucial in vivo extensively employed cancer research that has been shown to maintain the genomic characteristics and pathological structure of patients across various subtypes, metastatic, diverse treatment histories. Various strategies utilized PDX models can offer valuable insights into mechanisms tumor progression, drug resistance, development novel therapies. This review provides comprehensive overview establishment applications models. We present an history current status models, elucidate construction methodologies for different tumors, conduct comparative analysis highlight distinct advantages limitations this relation other are elucidated domain comprehending underlying therapy, which highlights broad fields chemotherapy, targeted delivery systems, combination antibody–drug conjugates radiotherapy. Furthermore, with multiomics single‐cell analyses also emphasized. application clinical personalized medicine additionally

Language: Английский

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Jak-Stat Signaling Induced by Interleukin-6 Family Cytokines in Hepatocellular Carcinoma

Cancers, Journal Year: 2019, Volume and Issue: 11(11), P. 1704 - 1704

Published: Nov. 1, 2019

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. It can be caused by chronic liver cell injury with resulting sustained inflammation, e.g., triggered infections hepatitis viruses B (HBV) and C (HCV). Death hepatocytes leads to activation compensatory mechanisms, which ultimately result in fibrosis cirrhosis. Another feature infiltration inflammatory cells, secrete cytokines chemokines that act directly on hepatocytes. Among several secreted proteins, members interleukin-6 (IL-6) family have emerged as important regulatory proteins might constitute an attractive target for therapeutic intervention. The IL-6-type activate multiple intracellular signaling pathways, especially Jak/STAT cascade has been shown crucial HCC development. In this review, we give overview about pathogenesis respect pathway. We highlight role mutations genes encoding involved cytokine/Jak/STAT axis summarize current knowledge IL-6 context. further discuss possible anti-cytokine therapies patients comparison already established therapies.

Language: Английский

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Semaphorins in Adult Nervous System Plasticity and Disease

Frontiers in Synaptic Neuroscience, Journal Year: 2021, Volume and Issue: 13

Published: May 11, 2021

Semaphorins, originally discovered as guidance cues for developing axons, are involved in many processes that shape the nervous system during development, from neuronal proliferation and migration to neuritogenesis synapse formation. Interestingly, expression of Semaphorins persists after development. For instance, Semaphorin 3A is a component perineuronal nets, extracellular matrix structures enwrapping certain types neurons adult CNS, which contribute closure critical period plasticity. 3G 4C play crucial role control hippocampal connectivity memory processes, 5A 7A regulate neurogenesis. This evidence points regulation In this review, we address distribution discuss their function physiological pathological processes.

Language: Английский

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