Editorial: Metaflammation in obesity and diabetes

Frontiers in Endocrinology, Год журнала: 2025, Номер 15

Опубликована: Янв. 16, 2025

Lifestyle diseases are indeed becoming life-threatening. Obesity and diabetes now considered as two major inflammatory that were in disguised over the years only metabolic diseases. Now there growing interests dissecting role of metaflammation well inflammation a cause and/or consequence for its direct contribution pathogenesis pathophysiology these life-threatening Since last decade, cutting-edge research demonstrated obesity one key mediators predisposing factors context beyond, including cancer. Intriguingly, has been presented promoter cancer through experimental clinical conducted throughout 10 [1][2].Keeping this mind, present topic was conceived with an aim to current updates on topics ranging from mechanistic insights consequences induced obesity, signaling defects/dysregulation cell death pathways endocrine network, response infectious agents etc. relevant progression diabetes. A total 7 contributions 8 countries received include 4 original 3 review articles. All reviews article described possible therapeutic options while rest articles emphasized obesity.Low-grade persistent is linked number serious health setbacks In compliance issues, study by Uroić et al. (https://doi.org/10.3389/fendo.2024.1335371) have revealed significantly close association between expression chemokine ligand/receptor pathological abnormalities obesity-induced viz. abundance CCR4 + T lymphocytes vs vascular inflammation, CXCR4 subsets albuminuria CXCR3 dyslipidemia axes proposed potential targets. addition, obese conditions due overfeeding during early post-natal period signal polycystic ovary syndrome (PCOS) insulin resistance evoking proinflammatory responses activating NLRP3 followed elevation IL-1β deactivating AMPK experimentally documented Veličković (https://doi.org/10.3389/fendo.2024.1402905). healthy individuals, antiinflammatory reverse episodes. Adiponectin (ADP) synthesized adipocytes known act anti-inflammatory adipokine links lipid metabolism glucose homeostasis regulate energy balance insulin-secretion prevent [3]. However, cross-sectional Nielsen Prevalence changes life-style, feed habits environmental increasing reports new fatal outcomes also emerging both developed developing countries. particular, threating world prevalence different subtypes [8], especially colorectal cancer.Interestingly, further complications editorial majorly Toll-like receptor (TLR4) summarized Figure 1. Whilst cytokines drives tumorigenesis inflammation-dysplasianeoplasia sequel. Created https://BioRender.com.Although

Язык: Английский

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RNA viruses, TLRs, and cytokines: the perfect storm?

Journal of Innate Immunity, Год журнала: 2025, Номер 17(1), С. 126 - 153

Опубликована: Янв. 16, 2025

The interactions between viruses and the host immune response are nuanced intricate. cytokine arguably plays a central role in dictating outcome of virus infection, balancing inflammation, healing, which is crucial to resolving infection without destructive immunopathologies. Early innate responses key generation beneficial or detrimental response. These initial regulated by plethora surface bound, endosomal, cytoplasmic receptors known as pattern recognition receptors. Of these, Toll-like (TLRs) play an important induction cytokines during infection. Recognizing pathogen-associated molecular patterns (PAMPs) such viral proteins and/or nucleotide sequences, TLRs act sentinels for initiation propagation responses. initiating single-stranded RNA (ssRNA) like influenza A (IAV), severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1), SARS-CoV-2, Middle East coronavirus, dengue virus, Ebola virus. Infection with these also associated aberrant expression proinflammatory that contribute harmful storm Herein we discuss connections ssRNA viruses, storm, roles TLRs.

Язык: Английский

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Plant-derived molecules in monkeypox management: insight and alternative therapeutic strategies

Beni-Suef University Journal of Basic and Applied Sciences, Год журнала: 2025, Номер 14(1)

Опубликована: Фев. 19, 2025

Abstract The WHO and CDC recently declared monkeypox virus (MPXV) a zoonotic disease known as (Mpox) Public Health Emergency of International Concern. According to the CDC, no treatment is specifically approved for Mpox infections. Medicinal plants are crucial in healthcare economic development, particularly low- middle-income countries. This review offers valuable insights into pathogenesis management through therapeutic approaches vaccination strategies using plant-based molecules. Core structural proteins necessary both viral entry immune response, including A29, H3L, L1R, involved MPXV. Potential targets vaccines include like A35R B6R, which essential propagation viruses. MPXV evades system by concealing its DNA, suppressing interferon limiting T NK cell activation, preventing apoptosis, complicating vaccine development. Antivirals (tecovirimat, brincidofovir) vaccinations (JYNNEOS, ACAM2000) manage Mpox. A recent study revealed early clinical trial results, indicating that antiviral drug tecovirimat, well-known conventional treatment, more effective than placebo against clade I type Research gaps, low effectiveness, availability challenges. novel perspective on combating global threat investigating alternative centered plant-derived compounds. Graphical

Язык: Английский

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In silico evidence of monkeypox F14 as a ligand for the human TLR1/2 dimer

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 17, 2025

Recent emergence of zoonotic monkeypox virus (Mpox) in human has triggered the virologists to develop plausible preventive measures. Hitherto, our understanding on mechanism immunopathogenesis Mpox infection is elusive. However, available experimental evidences suggest induction inflammation as main cause pathogenesis. Toll-like receptors (TLRs) are critical initiating and modulating host immune response pathogens. Inflammatory responses observed various poxvirus infections have, fact, been shown be mediated through TLR activation. Therefore, by silico approaches, this study seeks identify antigen(s) (MAg) that most likely interact with cell-surface TLRs. The proteomics data UniProt database contain 174 protein sequences, among which 105 immunoreactive proteins were modeled for 3D structure examined comparative protein-protein interactions TLRs molecular docking dynamics simulation. F14, an 8.28 kDa infective Mpox, was found exhibit strong binding affinity (ΔG=-12.5 Kcal mol-1) TLR1/2 dimer form a compact thermodynamically stable complex. Interestingly, significant level conformational change also both F14 TLR6 while forming F14-TLR1/2 Based these we propose putative ligand initiate proinflammatory signaling Mpox-infected host.

Язык: Английский

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Myeloid‐Driven Immune Suppression Subverts Neutralizing Antibodies and T Cell Immunity in Severe COVID‐19

Journal of Medical Virology, Год журнала: 2025, Номер 97(4)

Опубликована: Апрель 1, 2025

The objective of this study was to better understand immune failure mechanisms during severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 infection, which are critical for developing targeted vaccines and effective treatments. We collected 34 cases representing different disease severities performed high-quality single-cell TCR/BCR sequencing analyze the peripheral cell profiles. Additionally, we assessed antibody-neutralizing activity through in vitro experiments. Our integrated multiomics analysis uncovers a profound paradox COVID-19: hyperinflammation coexists with immunosuppression, driven by distinct yet interconnected dysregulatory mechanisms. Severe patients develop robust humoral immunity, evidenced clonally expanded plasma cells producing neutralizing antibodies (e.g., IGHG1-dominated responses) antigen-specific T activation. However, these protective responses counteracted myeloid-driven particularly CD14+ HMGB2+ monocytes exhibiting metabolic reprogramming HLA-DR downregulation, coupled progressive exhaustion characterized IFN-γ/TNF-α hyperactivation impaired antigen presentation. Importantly, prolonged viral persistence arises from coordinate cellular immunity-antibody-mediated neutralization cannot compensate defective cytotoxic function monocyte-mediated suppression. These findings highlight necessity therapeutic strategies that simultaneously enhance antibody effector functions Fc optimization), restore exhausted cells, reverse myeloid They also importance designed elicit balanced B memory durable responses, preventing progression. By addressing dual challenges such approaches could coordination improve outcomes COVID-19.

Язык: Английский

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Computational design of a glycosylated multi-epitope vaccine against HAsV-1 and HAsV-2 astrovirus for acute gastroenteritis

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 22, 2025

Язык: Английский

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