A5012920949- Connexins and lens biology
- Wound Healing and Treatments
- Heat shock proteins research
- Dermatologic Treatments and Research
- Pancreatic function and diabetes
- Barrier Structure and Function Studies
- Nicotinic Acetylcholine Receptors Study
- Exercise and Physiological Responses
- Bee Products Chemical Analysis
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Yersinia bacterium, plague, ectoparasites research
- Toxin Mechanisms and Immunotoxins
- Dermatology and Skin Diseases
- Diagnosis and Treatment of Venous Diseases
- Pluripotent Stem Cells Research
- Molecular Biology Techniques and Applications
- Corneal Surgery and Treatments
- Bacillus and Francisella bacterial research
- RNA Interference and Gene Delivery
- Hidradenitis Suppurativa and Treatments
- Adipose Tissue and Metabolism
- Advanced Glycation End Products research
- Burn Injury Management and Outcomes
- NF-κB Signaling Pathways
- Cancer Genomics and Diagnostics
FirstString Research (United States)
2011-2021
Medical University of South Carolina
2006-2019
JT Pharmaceuticals (United States)
2019
North Carolina State University
2002-2004
The gap junction protein, connexin43 (Cx43), has critical roles in the inflammatory, edematous, and fibrotic processes following dermal injury during wound healing, is abnormally upregulated at epidermal margins of venous leg ulcers (VLUs). Targeting Cx43 with ACT1, a peptide mimetic carboxyl-terminus Cx43, accelerates fibroblast migration proliferation, reepithelialization. In prospective, multicenter clinical trial conducted India, adults chronic VLUs were randomized to treatment an ACT1...
Aim: Gap-junctional connexin43 (Cx43) has roles in multiple aspects of skin wound healing – including scarring. The aim here was to study the effects a cell-permeant peptide from Cx43 carboxyl-terminus (CT) on scarring and regeneration following cutaneous injury. Materials & methods: CT were studied mouse pig models parameters assessed included neutrophil density, closure, granulation, tensile properties. Results: CT-peptide prompted decreases area scar progenitor tissue promoted restoration...
Nonhealing neuropathic foot ulcers remain a significant problem in individuals with diabetes. The gap-junctional protein connexin43 (Cx43) has roles dermal wound healing and targeting Cx43 signalling accelerates reepithelialization. In prospective, randomized, multicenter clinical trial we evaluated the efficacy safety of peptide mimetic C-terminus Cx43, alpha connexin carboxy-terminal (ACT1), accelerating chronic diabetic (DFUs) when incorporated into standard care (SOC) protocols. Adults...
Chronic inflammatory skin diseases may have a profound negative impact on the quality of life. Current treatment options be inadequate, offering an unsatisfactory response or side effects. Therefore, ongoing efforts exist to identify novel effective and safe treatments. Heat shock protein (HSP) 90 is chaperone that promotes activity wide range client proteins including key proinflammatory molecules involved in aberrant inflammation. Recently, proof-of-concept clinical trial 13 patients...
Background Heat shock protein 90 (HSP90) is an important chaperone supporting the function of many proinflammatory client proteins. Recent studies indicate HSP90 inhibition may be a novel mechanism action for inflammatory skin diseases; however, this has not been explored in atopic dermatitis (AD). Objectives Our study aimed to investigate as target treat AD. Methods Experimental models AD were used including primary human keratinocytes stimulated with cytokines (TNF/IFNγ or TNF/IL-4) and...
Treatment failure is a critical issue in breast cancer and identifying useful interventions that optimize current therapies remains unmet need. Expression functional studies have identified connexins (Cxs), family of gap junction proteins, as potential tumor suppressors. Studies suggest Cx43 has role cell proliferation, differentiation, migration. Although pan-gap drugs are available, the lack specificity these agents increases opportunity for off target effects. Consequently, therapeutic...
The alpha-carboxy terminus 1 (αCT1) peptide is a synthetically produced mimetic modified from the DDLEI C-terminus sequence of connexin 43 (Cx43). Previous research using various wound healing models have found promising therapeutic effects when applying drug, resulting in increased rates and reduced scarring. data suggested rapid metabolism rate vitro, creating an interest long term release. Using streptozotocin (STZ) type I diabetic rat model with surgically induced corneal injury, we...
HSP90 is a downstream regulator of tumour necrosis factor (TNF)-α and interleukin (IL)-17A signalling may therefore serve as novel target in the treatment psoriasis.This phase Ib proof-of-concept study was undertaken to evaluate safety efficacy inhibitor (RGRN-305) plaque psoriasis.We conducted an open-label, single-arm, dose-selection, single-centre study. Patients with psoriasis were treated 250 mg or 500 RGRN-305 daily for 12 weeks. Efficacy evaluated clinically using Psoriasis Area...
Increased apoptosis of pancreatic β-cells plays an important role in the occurrence and development type 2 diabetes. We examined effect diazoxide on β-cell its potential mechanism Otsuka Long Evans Tokushima Fatty (OLETF) rats, established animal model human diabetes, at prediabetic diabetic stages. found a significant increase with age frequency apoptosis, sequential enlargement islets, proliferation connective tissue surrounding accompanied defective insulin secretory capacity increased...
Phase II clinical trials have reported that acute treatment of surgical skin wounds with the therapeutic peptide alpha Connexin Carboxy-Terminus 1 (αCT1) improves cutaneous scar appearance by 47% 9-month postsurgery. While Cx43 and ZO-1 been identified as molecular targets αCT1, mode-of-action in mitigation at cellular tissue levels remains to be further characterized. Scar histoarchitecture αCT1 vehicle-control treated within same patient were compared using biopsies from a I trial 29-day...
Keratinocytes are the key cellular target for IL-17A-mediated effects in psoriasis and HSP90 is important signalling. RGRN-305 a novel inhibitor reported to reduce psoriatic phenotypes preclinical animal models. The aim of this study was investigate effect on psoriasis-like inflammatory response human keratinocytes vitro. Using RT-qPCR, we demonstrated significantly increased expression isoforms HSP90AB1, HSP90B1 TRAP1 lesional compared with non-lesional skin. In setting where were...
Abstract Retinoblastoma (Rb) is a common childhood intraocular cancer that affects approximately 300 children each year in the United States alone. 2‐Methoxyestradiol (2ME), an endogenous metabolite of 17‐β‐estradiol dose not bind to nuclear estrogen receptor, exhibits potent apoptotic activity against rapidly growing tumor cells. Here, we report 2ME induction apoptosis was demonstrated by early fragmented DNA after 48 h incubation with 10 µM Rb cell lines. Subsequently, decrease...
Importance Hidradenitis suppurativa is a painful immune-mediated disorder with limited treatment options; hence, need exists for new treatments. Objective To evaluate the feasibility of heat shock protein 90 inhibition by RGRN-305 as novel mechanism action in treating moderate to severe hidradenitis suppurativa. Design, Setting, and Participants This was parallel-design, double-blind, proof-of-concept, placebo-controlled randomized clinical trial conducted between September 22, 2021, August...