Molecular Insights into the Interaction of Cathepsin D and Iron in Chronic Wound Healing: Exploring Therapeutic Potential and Mechanisms

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 544 - 544

Published: Feb. 21, 2025

Background: Chronic wounds, such as diabetic ulcers, often fail to progress through healing due persistent inflammation, infections, and extracellular matrix (ECM) imbalances. Cathepsin D, an aspartate protease active in acidic environments, plays a pivotal role wound by mediating inflammatory responses, ECM remodeling, macrophage phenotype transitions. Its dysregulation, however, can impair healing, highlighting the need for targeted modulation of its activity. The aim this study was investigate molecular interaction between Fe2+ cathepsin D’s catalytic core ionic zipper under physiological conditions identify strategies enhance tissue repair accelerate chronic wounds. Methods: structure D obtained from Protein Data Bank (PDB) analyzed using UCSF Chimera. Molecular interactions ferrous ions (Fe2+) were studied, focusing on key residues (D33 D231) (E5, E180, D187). Results: Our results showed that form 96 kDa dimer, consisted heterodimers with distinct amino acid chains, where D33 D231 formed site, E5, D187 constituted zipper. A functional pocket containing conserved D231, essential proteolytic activity, identified. At pH (~7.5), exhibited most potent Fe2+, energies −7 × 1017 J at oxygen atoms carboxylate group (OD1) α-carbon (CA) atoms, whereas slightly lower −6 γ-carbon atom (CG) CA atoms. (~4), E5 primary interacting residue, shortest distance (2.69 Å), stable across several emphasizing metal binding. Conclusions: strongly influence Fe2. pH, demonstrate robust energetically efficient binding Fe2+. same time, conditions, emerges residue involved, potentially affecting D. These insights provide foundation targeting specific modulate presenting promising opportunities therapeutic aimed improving healing.

Language: Английский

The Journey of Copper-Impregnated Dressings in Wound Healing: From a Medical Hypothesis to Clinical Practice

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 562 - 562

Published: Feb. 24, 2025

Background/Objectives. Chronic wounds pose a substantial global healthcare burden exacerbated by aging populations and the increasing prevalence of conditions such as diabetes, peripheral vascular disease, venous insufficiency. Impaired physiological repair mechanisms, including angiogenesis, collagen synthesis, re-epithelialization, hinder healing process in chronic wounds. Many these processes are dependent on their interaction with copper. We hypothesized that targeted delivery copper ions to wound bed would enhance healing. Methods. Wound dressings impregnated oxide microparticles were designed ensure controlled release ions. The efficacy was evaluated using non-infected models, diabetic mouse models compared against control silver dressings. Outcome measures included closure rates, epidermal skin quality assessed histopathological examination, gene expression profiling. Clinical applications through diverse case studies trials involving management. Results. Copper significantly accelerated enhanced angiogenesis Histopathological analyses revealed faster granulation tissue formation, regeneration, neovascularization. Gene showed upregulation critical angiogenic factors VEGF HIF-1α. Investigations clinical observations corroborated improved across various types, Conclusions. is essential for healing, copper-impregnated provide promising solution By enhancing go beyond antimicrobial action, offering cost-effective innovative alternative conventional therapies. represent transformative advancement addressing challenges care.

Language: Английский

The Transformative Role of Nanotechnology in the Management of Diabetes Mellitus: Insights from Current Research

Biomolecules, Journal Year: 2025, Volume and Issue: 15(5), P. 653 - 653

Published: May 1, 2025

Nanotechnology refers to the science that modulates molecules nanoscale dimension. Nanomedicine, i.e., utilization of nanotechnology for diagnosing and treating several disorders, is a subject ongoing research. The concept behind nanomedicine in diabetes mellitus (DM) treatment stems from need ameliorate absorption distribution antidiabetic therapies order overcome barriers, namely pH throughout gastrointestinal tract, gut microbiota, temperature/heat difficulties incorporation drugs into cells. Thus, scope particularly challenging demanding, considering fact human body perpetually changing entity achieve homeostasis. In this review, we will delve various nanoparticles are being studied terms treatment, their pros cons expanding knowledge field. Despite seems be very promising, there still many gaps our understanding how addresses its utilization. Moreover, high costs, along with an as-yet unclear safety profile, remain significant barrier widespread adoption. describe both phytochemicals chemical compounds seeks exploit pave way more efficacious comprehensive management mellitus.

Language: Английский