Autoimmunity and organ damage in systemic lupus erythematosus

Nature Immunology, Год журнала: 2020, Номер 21(6), С. 605 - 614

Опубликована: Май 4, 2020

Язык: Английский

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Host–microbiota interactions in immune-mediated diseases

Nature Reviews Microbiology, Год журнала: 2020, Номер 18(9), С. 521 - 538

Опубликована: Май 26, 2020

Язык: Английский

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The Akt pathway in oncology therapy and beyond (Review)

International Journal of Oncology, Год журнала: 2018, Номер unknown

Опубликована: Окт. 16, 2018

Protein kinase B (Akt), similar to many other protein kinases, is at the crossroads of cell death and survival, playing a pivotal role in multiple interconnected signaling mechanisms implicated metabolism, growth division, apoptosis suppression angiogenesis. Akt displays important metabolic effects, among which are glucose uptake muscle fat cells or neuronal death. Disruptions Akt‑regulated pathways associated with cancer, diabetes, cardiovascular neurological diseases. The regulation pathway renders valuable therapeutic target. discovery process inhibitors using various strategies has led identification great selectivity, low side‑effects toxicity. usefulness emerges beyond cancer therapy extends major diseases, such as heart neurodegeneration. This review presents key features structure functions, progress regards drug development, their preclinical clinical activity efficacy safety for patients.

Язык: Английский

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T-cell Dysfunction in Glioblastoma: Applying a New Framework

Clinical Cancer Research, Год журнала: 2018, Номер 24(16), С. 3792 - 3802

Опубликована: Март 28, 2018

Abstract A functional, replete T-cell repertoire is an integral component to adequate immune surveillance and the initiation maintenance of productive antitumor responses. Glioblastoma (GBM), however, particularly adept at sabotaging immunity, eliciting severe dysfunction that both qualitative quantitative. Understanding countering such are among keys harnessing otherwise stark potential anticancer immune-based therapies. Although in GBM has been long described, newer immunologic frameworks now exist for reclassifying deficits a manner better permits their study reversal. Herein, we divide discuss various elicited by within context five relevant categories: senescence, tolerance, anergy, exhaustion, ignorance. Categorization appropriately made according molecular bases dysfunction. Likewise, review mechanisms which elicits each mode emerging immunotherapeutic strategies designed overcome them. Clin Cancer Res; 24(16); 3792–802. ©2018 AACR.

Язык: Английский

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Immune suppression in gliomas

Journal of Neuro-Oncology, Год журнала: 2020, Номер 151(1), С. 3 - 12

Опубликована: Июнь 15, 2020

The overall survival in patients with gliomas has not significantly increased the modern era, despite advances such as immunotherapy. This is part due to their notorious ability suppress local and systemic immune responses, severely restricting treatment efficacy.

Язык: Английский

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The science and medicine of human immunology

Science, Год журнала: 2020, Номер 369(6511)

Опубликована: Сен. 25, 2020

Although the development of effective vaccines has saved countless lives from infectious diseases, basic workings human immune system are complex and have required animal models, such as inbred mice, to define mechanisms immunity. More recently, new strategies technologies been developed directly explore with unprecedented precision. We discuss how these approaches advancing our mechanistic understanding immunology facilitating therapeutics for infection, autoimmune cancer.

Язык: Английский

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Hypothyroidism

Nature Reviews Disease Primers, Год журнала: 2022, Номер 8(1)

Опубликована: Май 19, 2022

Язык: Английский

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Sex differences in obesity, lipid metabolism, and inflammation—A role for the sex chromosomes?

Molecular Metabolism, Год журнала: 2018, Номер 15, С. 35 - 44

Опубликована: Апрель 12, 2018

Sex differences in obesity and related diseases are well established. Gonadal hormones a major determinant of these sex differences. However, body size composition evident prior to exposure gonadal hormones, providing evidence for gonadal-independent contributions attributable the XX or XY chromosome complement. Large-scale genetic studies have revealed male/female architecture adipose tissue amount anatomical distribution. typically neglected X Y chromosomes.Here we discuss how complement may influence obesity, lipid levels, inflammation. Human anomalies such as Klinefelter syndrome (XXY), mouse models with engineered alterations complement, support an important role chromosomes metabolism. In particular, Four Core Genotypes model-consisting mice either ovaries testes, testes-has effect dosage on adiposity, hyperlipidemia, inflammation irrespective male female gonads. Mechanisms include enhanced expression genes that escape inactivation.Although less studied than effects exert independent interactive metabolism, presence two has been associated increased adiposity dyslipidemia XXY men. The inactivation contribute, but more work is required.

Язык: Английский

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STING inhibitors target the cyclic dinucleotide binding pocket

Proceedings of the National Academy of Sciences, Год журнала: 2021, Номер 118(24)

Опубликована: Июнь 7, 2021

Cytosolic DNA activates cGAS (cytosolic sensor cyclic AMP-GMP synthase)-STING (stimulator of interferon genes) signaling, which triggers and inflammatory responses that help defend against microbial infection cancer. However, aberrant cytosolic self-DNA in Aicardi-Goutière's syndrome constituently active gain-of-function mutations STING STING-associated vasculopathy with onset infancy (SAVI) patients lead to excessive type I interferons proinflammatory cytokines, cause difficult-to-treat sometimes fatal autoimmune disease. Here, silico docking identified a potent antagonist SN-011 binds higher affinity the dinucleotide (CDN)-binding pocket than endogenous 2'3'-cGAMP. locks an open inactive conformation, inhibits cytokine induction activated by 2'3'-cGAMP, herpes simplex virus 1 infection, Trex1 deficiency, overexpression cGAS-STING, or SAVI mutants. In Trex1-/- mice, was well tolerated, strongly inhibited hallmarks inflammation autoimmunity disease, prevented death. Thus, specific inhibitor CDN-binding is promising compound for STING-driven

Язык: Английский

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SARS-CoV-2 vaccines and autoimmune diseases amidst the COVID-19 crisis

Rheumatology International, Год журнала: 2021, Номер 41(3), С. 509 - 518

Опубликована: Янв. 30, 2021

Coronavirus disease 2019 (COVID-19) pandemic has become challenging even for the most durable healthcare systems. It seems that vaccination, one of effective public-health interventions, presents a ray hope to end by achieving herd immunity. In this review, we aimed cover aspects current knowledge severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and vaccine candidates in light autoimmune inflammatory diseases (AIIDs) analyze their potential terms safety effectiveness patients with AIIDs. Therefore, focused narrative review was carried out predict possible implications different types SARS-CoV-2 which confer distinct immune mechanisms establish response protection against COVID-19: whole virus (inactivated or weakened), viral vector (replicating non-replicating), nucleic acid (RNA, DNA), protein-based (protein subunit, virus-like particle). Still, there is uncertainty among AIIDs clinicians about new vaccines. There are variety approaches towards building protective immunity SARS-CoV-2. Only high-quality clinical trials would clarify underlying immunological newly implemented vaccines/adjuvants living

Язык: Английский

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