Non-alcoholic fatty liver disease: the interplay between metabolism, microbes and immunity

Nature Metabolism, Год журнала: 2021, Номер 3(12), С. 1596 - 1607

Опубликована: Дек. 20, 2021

Язык: Английский

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Hemicyanine‐Based Near‐Infrared Activatable Probes for Imaging and Diagnosis of Diseases

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(51), С. 26454 - 26475

Опубликована: Июль 15, 2021

Molecular activatable probes with near-infrared (NIR) fluorescence play a critical role in vivo imaging of biomarkers for drug screening and disease diagnosis. With structural diversity high quantum yields, hemicyanine dyes have emerged as versatile scaffold the construction optical probes. This Review presents survey hemicyanine-based NIR (HNAPs) early diagnosis diseases. The molecular design principles HNAPs towards signaling against various are discussed focus on their broad applications detection diseases including inflammation, acute organ failure, skin diseases, intestinal cancer. progress not only proves unique value preclinical research but also highlights translational potential clinical

Язык: Английский

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Anakinra Therapy for Non-cancer Inflammatory Diseases

Frontiers in Pharmacology, Год журнала: 2018, Номер 9

Опубликована: Ноя. 6, 2018

Interleukin-1 (IL-1) is the prototypic inflammatory cytokine: two distinct ligands (IL-1α and IL-1β) bind IL-1 type 1 receptor (IL-1R1) induce a myriad of secondary mediators, including prostaglandins, cytokines chemokines. IL-1α constitutively present in endothelial epithelial cells whereas IL-1β inducible myeloid released following cleavage by caspase 1. Over past 30 years, IL-1-mediated inflammation has been established broad spectrum diseases, ranging from rare autoinflammatory diseases to common conditions such as gout rheumatoid arthritis, 2 diabetes, atherosclerosis, acute myocardial infarction. Blocking IL entered clinical arena with anakinra, recombinant form naturally occurring Receptor antagonist (IL 1Ra); 1Ra prevents binding 1α well 1β 1R1. Quenching 1-mediated detrimental consequences tissue damage organ dysfunction. Although anakinra presently approved for treatment arthritis cryopyrin-associated periodic syndromes, off-label use far exceeds its indications. Dosing 100 mg subcutaneously provides clinically evident benefits within days some used daily over 12 years. Compared other biologics, an unparalleled record safety opportunistic infections, particularly Mycobacterium tuberculosis are rare, even populations at risk reactivation latent infections. Because this excellent profile relative short duration action, can also be diagnostic tool undefined mediated trials treat cancer, review focuses on chronic diseases.

Язык: Английский

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The impact of the Fungus-Host-Microbiota interplay uponCandida albicansinfections: current knowledge and new perspectives

FEMS Microbiology Reviews, Год журнала: 2020, Номер 45(3)

Опубликована: Ноя. 18, 2020

Candida albicans is a major fungal pathogen of humans. It exists as commensal in the oral cavity, gut or genital tract most individuals, constrained by local microbiota, epithelial barriers and immune defences. Their perturbation can lead to outgrowth development mucosal infections such oropharyngeal vulvovaginal candidiasis, patients with compromised immunity are susceptible life-threatening systemic infections. The importance interplay between fungus, host microbiota driving transition from C. commensalism pathogenicity widely appreciated. However, complexity these interactions, significant impact fungal, variability upon disease severity outcome, less well understood. Therefore, we summarise features fungus that promote infection, how genetic variation clinical isolates influences pathogenicity. We discuss antifungal immunity, this differs mucosae, individual person's susceptibility infection. Also, describe factors influence composition gut, vaginal microbiotas, affect colonisation immunity. argue detailed understanding variables, which underlie fungal-host-microbiota will present opportunities for directed therapies benefit vulnerable patients.

Язык: Английский

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Gut Microbiota Interact With the Brain Through Systemic Chronic Inflammation: Implications on Neuroinflammation, Neurodegeneration, and Aging

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Апрель 7, 2022

It has been noticed in recent years that the unfavorable effects of gut microbiota could exhaust host vigor and life, yet knowledge theory are just beginning to be established. Increasing documentation suggests microbiota–gut–brain axis not only impacts brain cognition psychiatric symptoms but also precipitates neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), multiple sclerosis (MS). How blood–brain barrier (BBB), a machinery protecting central nervous system (CNS) from systemic circulation, allows risky factors derived translocated into seems paradoxical. For unique anatomical, histological, immunological properties underpinning its permeable dynamics, BBB regarded biomarker associated with neural pathogenesis. The permeability mice rats caused by GM dysbiosis raises question how metabolites change causes pathophysiology neuroinflammation neurodegeneration (NF&ND) aging, pivotal multidisciplinary field tightly immune chronic inflammation. If all, microbiota-induced inflammation (GM-SCI) mainly refers excessive mucosal immunity dysregulation, which is often influenced dietary components age, produced at interface intestinal (IB) or exacerbated after IB disruption, initiates various common diseases along dispersal routes, eventually impairs integrity cause NF&ND aging. To illustrate roles affected inflammatory “leaky” resulting their metabolites, we reviewed selected publications, including role barrier, influences on permeability, NF&ND, add depth bridging inflammation, plausible mechanism indispensable for corruption was highlighted; namely, maintenance cues cytokines, may help understand play major

Язык: Английский

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From Focal Lipid Storage to Systemic Inflammation

Journal of the American College of Cardiology, Год журнала: 2019, Номер 74(12), С. 1594 - 1607

Опубликована: Сен. 1, 2019

Язык: Английский

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The Role of Mitophagy in Innate Immunity

Frontiers in Immunology, Год журнала: 2018, Номер 9

Опубликована: Июнь 5, 2018

Mitochondria are cellular organelles essential for multiple biological processes, including energy production, metabolites biosynthesis, cell death and immunological responses among others. Recent advances in the field of immunology research reveal pivotal role metabolism innate immune cells fate function. Therefore, maintenance mitochondrial network integrity activity is a prerequisite system homeostasis. Mitochondrial selective autophagy, known as mitophagy, surveils population eliminating superfluous and/or impaired mediating survival viability response to injury/trauma infection. Defective removal damaged mitochondria leads hyperactivation inflammatory signaling pathways subsequently chronic systemic inflammation development diseases. Here, we review molecular mechanisms mitophagy highlight its critical

Язык: Английский

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Mediators of Inflammation

Springer eBooks, Год журнала: 2018, Номер unknown, С. 3 - 32

Опубликована: Янв. 1, 2018

Язык: Английский

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Mitochondria in the signaling pathways that control longevity and health span

Ageing Research Reviews, Год журнала: 2019, Номер 54, С. 100940 - 100940

Опубликована: Авг. 12, 2019

Genetic and pharmacological intervention studies have identified evolutionarily conserved functionally interconnected networks of cellular energy homeostasis, nutrient-sensing, genome damage response signaling pathways, as prominent regulators longevity health span in various species. Mitochondria are the primary sites ATP production key players several other important processes. Mitochondrial dysfunction diminishes tissue organ functional performance is a commonly considered feature aging process. Here we review evidence that through reciprocal multilevel interactions, mitochondria implicated lifespan modulation function these which altogether constitute highly dynamic complex system controls An characteristic pathways their extensive crosstalk apparent malleability to modification by non-invasive pharmacological, dietary, lifestyle interventions, with promising effects on animal models potentially also humans.

Язык: Английский

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Chloride regulates dynamic NLRP3-dependent ASC oligomerization and inflammasome priming

Proceedings of the National Academy of Sciences, Год журнала: 2018, Номер 115(40)

Опубликована: Сен. 19, 2018

The NLRP3 inflammasome is an important regulator of inflammation and immunity. It a multimolecular platform formed within cells that facilitates the activation proinflammatory caspases to drive secretion cytokines such as interleukin-1β (IL-1β). Knowledge mechanisms regulating formation incomplete. Here we report Cl- channel-dependent dynamic ASC oligomers specks remain inactive in absence K+ efflux. Formed after efflux exclusively, are dependent, reversible, inactive, although they further prime inflammatory responses, accelerating enhancing release IL-1β response efflux-inducing stimulus. NEK7 specific sensor does not associate with under conditions stimulating exclusively efflux, but activating complex driving inflammation. Our investigation delivers mechanistic understanding into regulation responses.

Язык: Английский

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