RESUMO
Diabetic wounds represent a significant healthcare burden and are characterized by impaired wound healing due to increased oxidative stress and persistent inflammation. We have shown that CNP-miR146a synthesized by the conjugation of cerium oxide nanoparticles (CNP) to microRNA (miR)-146a improves diabetic wound healing. CNP are divalent metal oxides that act as free radical scavenger, while miR146a inhibits the pro-inflammatory NFκB pathway, so CNP-miR146a has a synergistic role in modulating both oxidative stress and inflammation. In this study, we define the mechanism(s) by which CNP-miR146a improves diabetic wound healing by examining immunohistochemical and gene expression analysis of markers of inflammation, oxidative stress, fibrosis, and angiogenesis. We have found that intradermal injection of CNP-miR146a increases wound collagen, enhances angiogenesis, and lowers inflammation and oxidative stress, ultimately promoting faster closure of diabetic wounds.
Assuntos
Cério , Diabetes Mellitus , MicroRNAs , Nanopartículas , Cério/química , Cério/farmacologia , Humanos , MicroRNAs/metabolismo , Nanopartículas/química , CicatrizaçãoRESUMO
BACKGROUND: Diabetic wounds have become one of the most challenging public health issues of the 21st century, yet there is no effective treatment available. We have previously shown that the diabetic wound healing impairment is associated with increased inflammation and decreased expression of the regulatory microRNA miR-146a. We have conjugated miR-146a to cerium oxide nanoparticles (CNP-miR146a) to target reactive oxygen species (ROS) and inflammation. This study aimed to evaluate the consequences of CNP-miR146a treatment of diabetic wounds. STUDY DESIGN: Eight-millimeter wounds were created on the dorsal skin of Db/Db mice and treated with PBS or differing concentrations of CNP-mir146a (1; 10; 100; or 1,000 ng) at the time of wounding. Rate of wound closure was measured until the wounds were fully healed. At 4 weeks post-healing, a dumbbell-shaped skin sample was collected, with the healed wound in the center, and an Instron 5942 testing unit was used to measure the maximum load and modulus. RESULTS: Our data showed that diabetic wounds treated with PBS or 1 ng CNP-miR146a took 18 days to heal. Treatment with 10, 100, or 1,000 ng of CNP+miR-146a effectively enhanced healing, and wounds were fully closed at day 14 post-wounding. The healed skin from the CNP-miR146a-treated group showed a trend of improved biomechanical properties (increased maximum load and modulus), however it did not reach significance. CONCLUSIONS: We found that a 100-ng dose of CNP-miR146a improved diabetic wound healing and did not impair the biomechanical properties of the skin post-healing. This nanotechnology-based therapy is promising, and future studies are warranted to transfer this therapy to clinical application.
Assuntos
Cério/farmacologia , Complicações do Diabetes/terapia , MicroRNAs/farmacologia , Nanopartículas/química , Cicatrização/efeitos dos fármacos , Ferimentos Penetrantes/terapia , Animais , Modelos Animais de Doenças , Feminino , CamundongosRESUMO
BACKGROUND: Surgical burden is a large and neglected global health problem in low- and middle-income countries. With the increasing trauma burden, the goal of this study was to evaluate the trauma capacity of hospitals in the central plateau of Haiti. MATERIALS AND METHODS: The World Health Organization Emergency and Essential Surgical Care survey was adapted with a focus on trauma capacity. Interviewers along with translators administered the survey to key hospital staff. RESULTS: Seven hospitals in the region were surveyed. Of the hospitals surveyed, 3/7 had functioning surgical facilities. None of the hospitals had trauma registries. 71% of the hospitals had no formal trauma guidelines. 2/7 hospitals had a general surgeon available 100% of the time. All surgical facilities had oxygen cylinders available 100% of the time, but three of the primary level hospitals only had it available 51%-90% of the time. Intubation equipment was available at 57% of the facilities. Ventilators were only available in the operating room. Only the largest hospital had a computed tomography scanner. Other hospitals (66%) had a functioning x-ray machine 76%-90% of the time. Hospitals (57%) had an ultrasound machine. The most common reasons for referral were lack of appropriate facilities and supplies at the primary level care centers or lack of trained personnel at higher-level facilities. CONCLUSIONS: Trauma capacity in the central plateau of Haiti is limited. There is a great need for more personnel, trauma training at all staff levels, emergency care guidelines, trauma registries, and imaging equipment and training, specifically in ultrasonography. To accomplish this, coordination is needed between the Haitian government and local and international nongovernmental organizations.