Interplay of hypoxia, immune dysregulation, and metabolic stress in pathophysiology of type 1 diabetes DOI Creative Commons
Rahul Mittal, Joana Lemos, Prem P. Chapagain

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Июнь 4, 2025

Type 1 diabetes (T1D) is an autoimmune disease characterized by the progressive destruction of pancreatic β-cells, leading to insulin deficiency and chronic hyperglycemia. While immune-mediated mechanisms β-cell are well-recognized, emerging evidence highlights hypoxia as a silent yet critical contributor T1D pathogenesis. Hypoxia in islets arises from inflammation, vascular dysfunction, hyperglycemia, immune cell infiltration, creating microenvironment that exacerbates dysfunction amplifies responses. Hypoxia-inducible factors (HIFs) play dual role regulating adaptive maladaptive responses hypoxia, influencing survival, activation, oxidative stress. Specifically, promotes polarization macrophages toward pro-inflammatory M1 phenotype, enhances differentiation Th17 cells, impairs function regulatory T cells (Tregs), thereby shifting landscape sustained autoimmunity. This perspective discusses multifaceted driving dysregulation vulnerability well need for innovative research approaches target this pathway. We propose future directions emphasize development advanced experimental models mimic interplay between clinically relevant conditions. Furthermore, we highlight potential therapeutic strategies its downstream effects preserve modulate Collaborative efforts across disciplines will be crucial translating these insights into clinical innovations improve outcomes individuals with T1D.

Язык: Английский

Synergistic effects of recombinant expressed Fowlicidin and Thymosin α1 hybrid peptides in modulating inflammation and infection in avian macrophages DOI Creative Commons

Baseer Ahmad,

Zaheer Abbas,

Xubiao Wei

и другие.

Frontiers in Microbiology, Год журнала: 2025, Номер 16

Опубликована: Апрель 16, 2025

The hybrid FowlTα1 peptide represents a promising biomolecule synthesized from two naturally occurring peptides, namely Fowlicidins (Fowl) and Thymosin α1 (Tα1). This particular exhibits remarkable anti-inflammatory antimicrobial properties demonstrates the capacity to effectively interact with lipopolysaccharide (LPS), while simultaneously inducing minimal cytotoxicity hemolytic repercussions. Despite its potential, high cost of this has limited use. To overcome limitation, present study developed cost-effective biocompatible method for expressing in Pichia pastoris (P. pastoris). We obtained transgenic strain predicted molecular weight 3.1 kDa. was purified followed by reverse-phase high-performance liquid chromatography (RP-HPLC), yielding 7.2 mg purity 98.2%. Furthermore, physiochemical structural analysis revealed an amphipathic helical configuration that enhances bioactivity. Moreover, LPS-stimulated HD11 macrophages, significantly reduced release nitric oxide (NO), TNF-α, IL-6, IL-1β dose-dependent manner (p < 0.05) displayed robust activity against Escherichia coli (E. coli) compared conventional antibiotic. Overall, results highlighted production potential as novel therapeutic agent antimicrobial, anti-inflammatory, anti-endotoxin applications.

Язык: Английский

Процитировано

0
Longevity mechanisms in cardiac aging: exploring calcium dysregulation and senescence DOI
Neetu Agrawal, Muhammad Afzal, Waleed Hassan Almalki

и другие.

Biogerontology, Год журнала: 2025, Номер 26(3)

Опубликована: Апрель 21, 2025

Язык: Английский

Процитировано

0
SGO enhanced random forest and extreme gradient boosting framework for heart disease prediction DOI Creative Commons
Anima Naik, Ghanshyam G. Tejani, Seyed Jalaleddin Mousavirad

и другие.

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

Опубликована: Май 25, 2025

Abstract Cardiovascular disease (CVD) remains a leading global health concern, accounting for approximately 31.5% of deaths worldwide. According to the World Health Organization (WHO), over 20.5 million people succumb CVD each year—a figure projected rise 24.2 by 2030. Early diagnosis is critical and can be facilitated monitoring key risk factors such as cholesterol levels, blood pressure, diabetes, obesity. This study proposes heart prediction (HDP) model employing Random Forest (RF) eXtreme Gradient Boosting (XGB) classifiers. Both models are further optimized through hyperparameter tuning using Social Group Optimization (SGO) algorithm. The was developed validated Cleveland Statlog datasets from UCI repository. Pre-optimization results RF yielded an accuracy (Acc.) 84% ROC-AUC score 92.03% on dataset, 88.09% Acc. with 97.50% Statlog. XGB classifier achieved 81.97% 90.73% Cleveland, 92.86% 96.14% After SGO-based optimization, improved 95.08% 95.26% 95.24% 98.18% Similarly, reached 93.44% 97.62% These highlight effectiveness SGO in enhancing ML performance medical problems. However, has certain limitations. evaluation conducted solely two benchmark datasets, which may not fully reflect diversity complexity real-world clinical populations. Furthermore, external validation independent or real-time data performed, limit generalizability results. computational cost associated optimization also assessed. Future research should focus validating across broader assessing applicability, analyzing efficiency ensure scalability adoption.

Язык: Английский

Процитировано

0
Interplay of hypoxia, immune dysregulation, and metabolic stress in pathophysiology of type 1 diabetes DOI Creative Commons
Rahul Mittal, Joana Lemos, Prem P. Chapagain

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Июнь 4, 2025

Type 1 diabetes (T1D) is an autoimmune disease characterized by the progressive destruction of pancreatic β-cells, leading to insulin deficiency and chronic hyperglycemia. While immune-mediated mechanisms β-cell are well-recognized, emerging evidence highlights hypoxia as a silent yet critical contributor T1D pathogenesis. Hypoxia in islets arises from inflammation, vascular dysfunction, hyperglycemia, immune cell infiltration, creating microenvironment that exacerbates dysfunction amplifies responses. Hypoxia-inducible factors (HIFs) play dual role regulating adaptive maladaptive responses hypoxia, influencing survival, activation, oxidative stress. Specifically, promotes polarization macrophages toward pro-inflammatory M1 phenotype, enhances differentiation Th17 cells, impairs function regulatory T cells (Tregs), thereby shifting landscape sustained autoimmunity. This perspective discusses multifaceted driving dysregulation vulnerability well need for innovative research approaches target this pathway. We propose future directions emphasize development advanced experimental models mimic interplay between clinically relevant conditions. Furthermore, we highlight potential therapeutic strategies its downstream effects preserve modulate Collaborative efforts across disciplines will be crucial translating these insights into clinical innovations improve outcomes individuals with T1D.

Язык: Английский

Процитировано

0