Podiatry Commons^™

Bone Healing During A Dysregulated Inflammatory Phase: Comparative Skeletal Features In 5-Lipoxygenase Knockout And Wild Type Mice, Marco Hernandez, Nidhin John, Bhuvana L. Chandrashekar, Mariza A. Matsumoto, Naohiro Shibuya, Claudia Biguetti

School of Podiatric Medicine - Student Research

Background: High-risk patients, such as those with diabetic neuropathy, often experience prolonged and dysregulated inflammation during bone healing. The 5-lipoxygenase (5LO) pathway is a key mediator of inflammation and bone resorption and may influence these outcomes. Therefore, understanding the skeletal features associated with 5LO genetic deletion may help identify therapeutic opportunities to improve healing in high-risk patients.

Objective: To determine how genetic deletion of 5LO affects skeletal structure and macrophage phenotypes, with the goal of identifying therapeutic targets to improve bone healing in high-risk patients.

Materials and Methods: A total of 10, adult (3 months old), 129/SvEv male mice were …

Comparative Analysis Of M1 And M2 Macrophage Distribution And Localization In Chronic Wounds Of Metabolically Healthy And Diabetic Hosts Using A C57bl/6 Mouse Model, Bryan Liu, Ramiro Cisneros, Nathaniel Primous, Estephania Garcia, Bhuvana Lakkasetter Chandrashekar, Claudia Biguetti

School of Podiatric Medicine - Student Research

Introduction/Purpose: Type 2 diabetes and obesity are major risk factors for delayed wound healing in chronic foot ulcers. This study investigated whether a high-fat diet induces diabetes-like metabolic dysfunction in mice and characterized associated morphological changes and macrophage polarization during wound healing. Macrophages exist as pro-inflammatory M1 and anti-inflammatory M2 phenotypes that regulate tissue repair.

Methods: Ten male C57BL/6J mice (8 weeks old) were divided into high-fat diet (HFD) and regular diet (RD) (IACUC Protocol 22-33) groups.  After 12 weeks, body weight and intraperitoneal glucose tolerance test were measured to confirm metabolic phenotypes, after which a 6mm dorsal excision wound …

Expression Of 5-Lo In Chronic Wounds In A Preclinical Murine Model Of Obesity And Type 2 Diabetes, Joshua Wu, Ramiro Cisneros, Nathaniel Primous, Estephania Garcia, Bhuvana Lakkasetter, Claudia Biguetti

School of Podiatric Medicine - Student Research

Introduction: Diabetes is associated with impaired wound healing and a high incidence of chronic, non-healing ulcers, largely driven by persistent low-grade inflammation. Leukotriene B4 (LTB4), a product of the 5-lipoxygenase (5-LO) pathway, has emerged as a key mediator of this chronic inflammatory state. Hence, this study investigated the role of the 5-LO pathway in cutaneous wound healing under normoglycemic and diabetic conditions using a murine model.

Methods: Twelve 8-week-old male C57BL/6J mice were fed with high-fat diet (HFD; 60% kcal fat) or low-fat diet (LFD; 10% kcal fat) for 12 weeks (IACUC 22-33). Body weight (BW) and fasting blood glucose …

The Multiple Roles Of 5-Lo In Tissue Regeneration – Insights From Translational Animal Models Utilizing Pharmacological And Genetic Approaches, Roel Navarro, Nidhin John, Claudia Biguetti

School of Podiatric Medicine - Student Research

Inflammation following tissue injury is a natural physiological response, where its course, duration, and intensity help determine whether it promotes beneficial or detrimental outcomes in tissue healing. Arachidonic acid (AA) serves as a substrate for5-lipoxygenase (5-LO) pathway, which synthesizes metabolites such as leukotrienes that influence both acute and chronic inflammatory response.  AA and its product's inhibitors are currently used to treat hypersensitivity reactions. However, literature suggests potential therapeutic efficacy in tissue healing.

Home-Based Electrical Stimulation To Accelerate Wound Healing-A Double-Blinded Randomized Control Trial, Alejandro Zulbaran-Rojas, Catherine Park, Nesreen El-Refaei, Brian Lepow, Bijan Najafi

Center on Aging Staff Publications

Background: Electrical stimulation (E-Stim) may offer a unique adjunctive treatment to heal complicated diabetic foot ulcers (DFU). Our primary goal is to examine the effectiveness of daily home-based E-Stim therapy to speed-up wound healing.

Methods: Patients with chronic DFUs and mild to severe peripheral arterial disease (PAD) were recruited and randomized to either control (CG) or intervention (IG) groups. The IG received 1-hour home-based E-Stim therapy on daily basis for 4 weeks (4W). E-Stim was delivered through electrical pads placed above the ankle joint using a bio-electric stimulation technology (BEST®) platform (Tennant Biomodulator® PRO). The CG was provided with an …

Characterization Of The Protective Role Of Regulatory T Cells In Experimental Periapical Lesions Development And Its Chemoattraction Manipulation As A Therapeutic Tool, Carolina Favaro Francisconi, Andreia Espindola Vieira, Cláudia Cristina Biguetti, Andrew J. Glowacki, Ana Paula Favaro Trombone, Ariadne Letra, Renato Menezes Silva, Charles S. Sfeir, Steven R. Little, Gustavo P. Garlet

School of Podiatric Medicine Publications

Introduction

The pathogenesis of periapical lesions is determined by the balance between host pro-inflammatory immune response and counteracting anti-inflammatory and reparative responses, which include regulatory T cells (Tregs) as potential immunoregulatory agents. In this study, we investigated (in a cause-and-effect manner) the involvement of CCL22-CCR4 axis in Tregs migration to the periapical area and the role of Tregs in the determination of outcomes in periapical lesions.

Methods

Periapical lesions were induced in C57Bl/6 (WT) and CCR4KO mice (pulp exposure and bacterial inoculation), and treated with anti-GITR to inhibit Tregs function or alternatively with CCL22-releasing, PLGA particles to induce site-specific migration …