Dual‐Nanoparticle Engineered Hydrogel Reverses Bicellular Oxidative Stress to Accelerate Diabetic Fracture Healing DOI Creative Commons
Yanzhi Zhao, Weixian Hu, Shengming Zhang

и другие.

Advanced Functional Materials, Год журнала: 2025, Номер unknown

Опубликована: Май 22, 2025

Abstract Impaired fracture healing in diabetic patients poses a persistent clinical challenge, with underlying mechanisms that remain to be fully elucidated. These findings reveal high glucose microenvironments generate excessive reactive oxygen species bone marrow mesenchymal stem cells (BMSCs) and marrow‐derived macrophages (BMDMs), leading mitochondrial dysfunction metabolic impairment. pathophysiological disruptions suppress osteogenic differentiation BMSCs while driving pro‐inflammatory polarization BMDMs, processes closely tied high‐glucose‐induced inhibition of Adenosine 5′‐monophosphate‐activated protein kinase (AMPK) phosphorylation. Restoration AMPK phosphorylation emerges as pivotal strategy mitigate oxidative stress restore cellular function. To address this, dual‐targeted therapeutic system (DLNPs@HA hydrogel) is developed combines anti‐CD105‐antibody‐modified nanoliposomes phosphatidylserine‐modified nanoliposomes, both encapsulating the specific activator α‐lipoic acid. This hydrogel facilitates sustained nanoparticle release, enabling precise effective delivery BMDMs. In vitro, DLNPs@HA successfully enhances activity suppresses inflammatory responses. vivo, it accelerates mice. By precisely targeting BMDMs reversing bicellular stress, this integrative medical‐engineering provides promising translatable solution for repair, seamlessly bridging mechanistic insights innovation.

Язык: Английский

Opposite causal effects of type 2 diabetes and metformin on Alzheimer's disease DOI Creative Commons
Dongming Liu, Hongbao Cao, Ancha Baranova

и другие.

The Journal of Prevention of Alzheimer s Disease, Год журнала: 2025, Номер unknown, С. 100129 - 100129

Опубликована: Март 1, 2025

Type 2 diabetes (T2D) is commonly co-morbid with Alzheimer's disease (AD). However, it remains unclear whether T2D itself or the antidiabetic drug metformin contributes to progression of AD. This study aimed investigate overall and independent effects use on risk Summary genome-wide association datasets were utilized for Mendelian randomization (MR) multivariable MR (MVMR) analyses, including ones (N = 455,017), 456,276), AD 453,733). Additionally, using proportional imbalance method, we analyzed AD-related adverse events in FDA Adverse Event Reporting System (FAERS) database (covering Q1 2004 Q2 2024). Our two-sample analysis indicated that not associated (OR: 1.03, CI: 0.99-1.08, P 0.128). while statistically significant, genetic signature exposure demonstrated a trend toward an increased 1.05, 1.00-1.09, 0.053). Interestingly, MVMR analysis, which evaluates T2D, found robust decrease 0.82, 0.68-0.98, 0.031), was higher 1.26, 1.06-1.50, 9.45E-3). In FAERS database, total 228,283 metformin-related event reports from 67,742 cases found. For as target event, signal reported 29 (ROR: 0.83, 95 % 0.58-1.19, 0.3126). reveals opposite causal These findings highlight importance assessing when prescribing patients T2D.

Язык: Английский

Процитировано

0
Noninvasive electrical stimulation enhances the diabetic osseointegration via alleviating mitochondrial damage DOI Creative Commons

Dongzong Huang,

Rongchen Xu,

Changzhen Xu

и другие.

View, Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

Abstract A high‐glucose environment induces an imbalance in mitochondrial homeostasis, and further results decreased autophagic capacity energy metabolism mitochondria. This dysfunction inhibits the regeneration of bone tissue. Electrical stimulation (ES) is efficient strategy to rebalance homeostasis accelerate process. However, traditional ES strategies are invasive easily cause secondary trauma, limiting their medical application. Here, we designed a new noninvasive direct‐current electric field (DCEF) strategy. can provide situ without implantation. The show that this target regulate through PI3K–AKT signaling pathway, activate autophagy, alleviate high‐glucose‐induced damage, promote osteogenic differentiation marrow mesenchymal stem cells. Consequently, exogenous effectively repair defects alleviating damage.

Язык: Английский

Процитировано

0
Dual‐Nanoparticle Engineered Hydrogel Reverses Bicellular Oxidative Stress to Accelerate Diabetic Fracture Healing DOI Creative Commons
Yanzhi Zhao, Weixian Hu, Shengming Zhang

и другие.

Advanced Functional Materials, Год журнала: 2025, Номер unknown

Опубликована: Май 22, 2025

Abstract Impaired fracture healing in diabetic patients poses a persistent clinical challenge, with underlying mechanisms that remain to be fully elucidated. These findings reveal high glucose microenvironments generate excessive reactive oxygen species bone marrow mesenchymal stem cells (BMSCs) and marrow‐derived macrophages (BMDMs), leading mitochondrial dysfunction metabolic impairment. pathophysiological disruptions suppress osteogenic differentiation BMSCs while driving pro‐inflammatory polarization BMDMs, processes closely tied high‐glucose‐induced inhibition of Adenosine 5′‐monophosphate‐activated protein kinase (AMPK) phosphorylation. Restoration AMPK phosphorylation emerges as pivotal strategy mitigate oxidative stress restore cellular function. To address this, dual‐targeted therapeutic system (DLNPs@HA hydrogel) is developed combines anti‐CD105‐antibody‐modified nanoliposomes phosphatidylserine‐modified nanoliposomes, both encapsulating the specific activator α‐lipoic acid. This hydrogel facilitates sustained nanoparticle release, enabling precise effective delivery BMDMs. In vitro, DLNPs@HA successfully enhances activity suppresses inflammatory responses. vivo, it accelerates mice. By precisely targeting BMDMs reversing bicellular stress, this integrative medical‐engineering provides promising translatable solution for repair, seamlessly bridging mechanistic insights innovation.

Язык: Английский

Процитировано

0