Innate immune mechanisms of mRNA vaccines

Immunity, Год журнала: 2022, Номер 55(11), С. 1993 - 2005

Опубликована: Ноя. 1, 2022

Язык: Английский

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Macrophage polarization and metabolism in atherosclerosis

Cell Death and Disease, Год журнала: 2023, Номер 14(10)

Опубликована: Окт. 20, 2023

Abstract Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of fatty deposits in inner walls vessels. These plaques restrict blood flow and lead to complications such as heart attack or stroke. The development atherosclerosis influenced variety factors, including age, genetics, lifestyle, underlying health conditions high pressure diabetes. Atherosclerotic stable form are slow growth, which leads luminal stenosis, with low embolic potential unstable form, contributes risk for thrombotic rapid clinical onset. In this complex scenario atherosclerosis, macrophages participate whole process, initiation, growth eventually rupture wound healing stages artery plaque formation. Macrophages exhibit heterogeneity plasticity, affect evolving microenvironment, e.g., leading excessive lipid accumulation, cytokine hyperactivation, hypoxia, apoptosis necroptosis. metabolic functional transitions response microenvironmental factors not only influence ongoing imminent responses within lesions but also directly dictate atherosclerotic progression regression. review, we discuss origin plaques, their phenotypic diversity, shifts, fate roles they play dynamic atherosclerosis. It describes how interact other cells, particularly T cells. Ultimately, targeting pathways involved macrophage polarization may innovative promising approaches precision medicine. Further insights into landscape biological features offer valuable information optimizing future treatment macrophages.

Язык: Английский

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Long Covid: where we stand and challenges ahead

Cell Death and Differentiation, Год журнала: 2022, Номер unknown

Опубликована: Сен. 7, 2022

Abstract Post-acute sequelae of SARS-CoV-2 (PASC), also known as Post-Covid Syndrome, and colloquially Long Covid, has been defined a constellation signs symptoms which persist for weeks or months after the initial infection. PASC affects wide range diverse organs systems, with manifestations involving lungs, brain, cardiovascular system other such kidney neuromuscular system. The pathogenesis is complex multifactorial. Evidence suggests that seeding persistence in different organs, reactivation, response to unrelated viruses EBV, autoimmunity, uncontrolled inflammation are major drivers PASC. relative importance pathogenetic pathways may differ tissue organ contexts. vaccination, addition protecting against disease, reduces breakthrough infection although its actual impact remains be defined. represents formidable challenge health care systems dissecting mechanisms pave way targeted preventive therapeutic approaches.

Язык: Английский

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xTrimoPGLM: Unified 100B-Scale Pre-trained Transformer for Deciphering the Language of Protein

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июль 6, 2023

Protein language models have shown remarkable success in learning biological information from protein sequences. However, most existing are limited by either autoencoding or autoregressive pre-training objectives, which makes them struggle to handle understanding and generation tasks concurrently. We propose a unified model, xTrimoPGLM, address these two types of simultaneously through an innovative framework. Our key technical contribution is exploration the compatibility potential for joint optimization has led strategy training xTrimoPGLM at unprecedented scale 100 billion parameters 1 trillion tokens. extensive experiments reveal that 1) significantly outperforms other advanced baselines 18 benchmarks across four categories. The model also facilitates atomic-resolution view structures, leading 3D structural prediction surpasses model-based tools. 2) not only can generate de novo sequences following principles natural ones, but perform programmable after supervised fine-tuning (SFT) on curated These results highlight substantial capability versatility generating sequences, contributing evolving landscape foundation science.

Язык: Английский

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The gasdermin family: emerging therapeutic targets in diseases

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Апрель 7, 2024

Abstract The gasdermin (GSDM) family has garnered significant attention for its pivotal role in immunity and disease as a key player pyroptosis. This recently characterized class of pore-forming effector proteins is orchestrating processes such membrane permeabilization, pyroptosis, the follow-up inflammatory response, which are crucial self-defense mechanisms against irritants infections. GSDMs have been implicated range diseases including, but not limited to, sepsis, viral infections, cancer, either through involvement pyroptosis or independently this process. regulation GSDM-mediated gaining recognition promising therapeutic strategy treatment various diseases. Current strategies inhibiting GSDMD primarily involve binding to GSDMD, blocking cleavage GSDMD-N-terminal (NT) oligomerization, albeit with some off-target effects. In review, we delve into cutting-edge understanding interplay between elucidate activation GSDMs, explore their associations diseases, discuss recent advancements potential developing inhibitors.

Язык: Английский

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A critical review of Ginger’s (Zingiber officinale) antioxidant, anti-inflammatory, and immunomodulatory activities

Frontiers in Nutrition, Год журнала: 2024, Номер 11

Опубликована: Июнь 6, 2024

Ginger ( Zingiber officinale ) is a rhizome that has been used as healthy herbal plant for years. Ginger’s chemical components are recognized to provide beneficial health effects, namely antioxidants and anti-inflammatory agents with the potential operate immunomodulators. This literature review covers numerous publications concerning ginger’s immunomodulatory potential, associated antioxidant effects in modifying body’s immune system. Pathophysiology of oxidative stress inflammation were introduced before diving deep down into plants an immunomodulator. properties provided by gingerol, shogaols, paradol, zingerone. mechanism linked Nrf2 signaling pathway activation. Its Akt inhibition NF-KB activation, triggering release cytokines while reducing proinflammatory cytokines. consumption food drink was also explored. Overall, ginger its active have shown strong reduce inflammation. Challenges future prospects elaborated development. Future collaborations between researchers from various fields, including chemists, biologists, clinicians, pharmacists, industry, required further investigate effect on human immunity. Collaboration industry can help accelerate advancement applications.

Язык: Английский

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Alleviating hypoxia to improve cancer immunotherapy

Oncogene, Год журнала: 2023, Номер 42(49), С. 3591 - 3604

Опубликована: Окт. 26, 2023

Язык: Английский

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TLRs: Innate Immune Sentries against SARS-CoV-2 Infection

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(9), С. 8065 - 8065

Опубликована: Апрель 29, 2023

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been responsible for a devastating pandemic since March 2020. Toll-like receptors (TLRs), crucial components in the initiation of innate immune responses to different pathogens, trigger downstream production pro-inflammatory cytokines, interferons, and other mediators. It demonstrated that they contribute dysregulated response observed patients with COVID-19. TLR2, TLR3, TLR4 TLR7 have associated COVID-19 severity. Here, we review role TLRs etiology pathogenesis COVID-19, including TLR3 rare variants, L412F polymorphism negatively regulates anti-SARS-CoV-2 responses, TLR3-related cellular senescence, interaction TLR2 SARS-CoV-2 proteins implication NET formation SARS-CoV-2. The activation contributes viral clearance resolution. However, may represent double-edged sword which elicit signaling, leading proinflammatory mediators, resulting disease. TLR-dependent excessive inflammation antiviral tip balance towards former or latter, altering equilibrium drives severity

Язык: Английский

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The relationship between gut microbiota and COVID-19 progression: new insights into immunopathogenesis and treatment

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Май 2, 2023

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) has posed a global health crisis. Increasing evidence underlines the key role of competent immune responses in resisting SARS-CoV-2 infection and manifests disastrous consequence host dysregulation. Elucidating mechanisms responsible for deregulated immunity COVID-19 may provide theoretical basis further research on new treatment modalities. Gut microbiota comprises trillions microorganisms colonizing human gastrointestinal tract vital homeostasis gut-lung crosstalk. Particularly, can lead to disruption gut equilibrium, condition called dysbiosis. Due its regulatory effect immunity, recently received considerable attention field immunopathology. Imbalanced fuel progression through production bioactive metabolites, intestinal metabolism, enhancement cytokine storm, exaggeration inflammation, regulation adaptive other aspects. In this review, we an overview alterations patients, their effects individuals’ susceptibility viral progression. Moreover, summarize currently available data critical bidirectional between microbes SARS-CoV-2-induced pathology, highlight immunomodulatory contributing pathogenesis. addition, discuss therapeutic benefits future perspectives microbiota-targeted interventions including faecal transplantation (FMT), bacteriotherapy traditional Chinese medicine (TCM) treatment.

Язык: Английский

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Systemic inflammation index, disease severity, and mortality in patients with COVID-19: a systematic review and meta-analysis

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Июнь 21, 2023

Introduction An excessive systemic pro-inflammatory state increases the risk of severe disease and mortality in patients with coronavirus 2019 (COVID-19). However, there is uncertainty regarding whether specific biomarkers inflammation can enhance stratification this group. We conducted a systematic review meta-analysis to investigate an emerging biomarker derived from routine hematological parameters, index (SII), COVID-19 different severity survival status. Methods A literature search was PubMed, Web Science, Scopus, between 1 st December 15 th March 2023. Risk bias certainty evidence were assessed using Joanna Briggs Institute Critical Appraisal Checklist Grades Recommendation, Assessment, Development Evaluation, respectively (PROSPERO registration number: CRD42023420517). Results In 39 studies, or non-survivor status had significantly higher SII values on admission compared non-severe survivor (standard mean difference (SMD)=0.91, 95% CI 0.75 1.06, p<0.001; moderate evidence). The also associated death 10 studies reporting odds ratios (1.007, 1.001 1.014, p=0.032; very low evidence) six hazard (1.99, 1.01 3.92, p=0.047; Pooled sensitivity, specificity, area under curve for 0.71 (95% 0.67 0.75), 0.64 0.77), 0.77 0.73 0.80), respectively. meta-regression, significant correlations observed SMD albumin, lactate dehydrogenase, creatinine, D-dimer. Discussion Our has shown that COVID-19. Therefore, inflammatory haematological parameters be helpful early Systematic https://www.crd.york.ac.uk/PROSPERO , identifier CRD42023420517.

Язык: Английский

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