ABSTRACT
BACKGROUND: Skin aging is an inevitable process with one of the key features of aging being dryness or flakiness of the skin. Previous in vivo and in vitro testing has highlighted that a silk-based product may be effective in improving moisture retention in skin. METHODS: We evaluated the safety and efficacy of our silk-based product through a combination of objective- including scanning electron microscopy (SEM) and EpiDerm Skin Irritation tests - and subjective tests - including direct evaluation of patient's own perception of their skin. RESULTS: In alignment with previous studies, patients reported significant concerns about aging, wrinkling, or saggy skin. We found that our silk-based product was safe and effective in improving hydration and resilience of facial skin and a majority of participants stated they would continue to use this product, when commercially available. CONCLUSION: Our novel silk-based product, NanoSilk Cosmo, is safe for use on human facial skin and it improves skin resiliency and hydration.
Subject(s)
Emollients , Skin Aging , Humans , Perception , Skin , Skin Care , Skin CreamABSTRACT
Acute respiratory distress syndrome (ARDS) is a devastating pulmonary disease with significant in-hospital mortality and is the leading cause of death in COVID-19 patients. Excessive leukocyte recruitment, unregulated inflammation, and resultant fibrosis contribute to poor ARDS outcomes. Nanoparticle technology with cerium oxide nanoparticles (CNP) offers a mechanism by which unstable therapeutics such as the anti-inflammatory microRNA-146a can be locally delivered to the injured lung without systemic uptake. In this study, we evaluated the potential of the radical scavenging CNP conjugated to microRNA-146a (termed CNP-miR146a) in preventing acute lung injury (ALI) following exposure to bleomycin. We have found that intratracheal delivery of CNP-miR146a increases pulmonary levels of miR146a without systemic increases, and prevents ALI by altering leukocyte recruitment, reducing inflammation and oxidative stress, and decreasing collagen deposition, ultimately improving pulmonary biomechanics.
Subject(s)
Bleomycin/adverse effects , Cerium , Drug Delivery Systems , MicroRNAs , Respiratory Distress Syndrome/drug therapy , Animals , Bleomycin/pharmacology , COVID-19/genetics , COVID-19/metabolism , Cerium/chemistry , Cerium/pharmacology , Disease Models, Animal , Male , Mice , MicroRNAs/chemistry , MicroRNAs/pharmacology , Respiratory Distress Syndrome/chemically induced , Respiratory Distress Syndrome/genetics , Respiratory Distress Syndrome/metabolism , SARS-CoV-2/metabolism , COVID-19 Drug TreatmentABSTRACT
Diabetes mellitus is a metabolic disorder associated with properties and an increased risk of chronic wounds due to sustained pro-inflammatory response. We have previously of radical scavenging cerium oxide nanoparticles (CNP) conjugated to the anti-inflammatory microRNA (miR)-146a, termed CNP-miR146a, improves diabetic wound healing by synergistically lowering oxidative stress and inflammation, and we sought to evaluate this treatment in a topical application. Silk fibroin is a biocompatible polymer that can be fabricated into nanostructures, termed nanosilk. Nanosilk is characterized by a high strength-to-density ratio and an ability to exhibit strain hardening. We therefore hypothesized that nanosilk would strengthen the biomechanical properties of diabetic skin and that nanosilk solution could effectively deliver CNP-miR146a to improve diabetic wound healing. The ability of nanosilk to deliver CNP-miR146a to murine diabetic wounds and improve healing was assessed by the rate of wound closure and inflammatory gene expression, as well as histologic analysis. The effect of nanosilk on the properties of human diabetic skin was evaluated by testing the biomechanical properties following topical application of a 7% nanosilk solution. Diabetic murine wounds treated with topical nanosilk and CNP-miR146a healed by day 14.5 compared to day 16.8 in controls (p = 0.0321). Wounds treated with CNP-miR146a had higher collagen levels than controls (p = 0.0126) with higher pro-fibrotic gene expression of TGFß-1 (p = 0.0092), Col3α1 (p = 0.0369), and Col1α2 (p = 0.0454). Treatment with CNP-miR146a lowered pro-inflammatory gene expression of IL-6 (p = 0.0488) and IL-8 (p = 0.0009). Treatment of human diabetic skin with 7% nanosilk solution resulted in significant improvement in maximum load and modulus (p < 0.05). Nanosilk solution is able to strengthen the biomechanical properties of diabetic skin and can successfully deliver CNP-miR146a to improve diabetic wound healing through inhibition of pro-inflammatory gene signaling and promotion of pro-fibrotic processes.
Subject(s)
Cerium/administration & dosage , Diabetes Mellitus, Experimental/drug therapy , MicroRNAs/administration & dosage , Nanoparticles/administration & dosage , Silk/administration & dosage , Skin Physiological Phenomena/drug effects , Wound Healing/drug effects , Animals , Biomechanical Phenomena , Cerium/chemistry , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/pathology , Female , Gene Expression/drug effects , Humans , Mice , MicroRNAs/chemistry , Nanoparticles/chemistry , Silk/chemistry , Skin/drug effects , Skin/metabolism , Skin/pathologyABSTRACT
BACKGROUND: Biliary atresia (BA) is an inflammatory pediatric cholangiopathy with only surgical means for treatment. Many contributors to bile acid synthesis and transport have previously been reported to be downregulated in patients with BA; yet, the driving factors of the abnormal bile acid synthesis and transport in regard to BA have not been previously studied. MATERIALS AND METHODS: Wild type or Ig-α-/- mice were injected with salt solution (control) or rotavirus on day of life 0, and analyses were performed on day of life 14. The mRNA levels of bile acid transporters/nuclear receptors and liver microRNAs (miRNAs) were compared between groups. A mouse hepatocyte cell line was used to examine the effects of innate cytokines on miRNA levels and bile acid transporter/nuclear receptor expression and miRNAs on bile acid transporter/nuclear receptor expression. RESULTS: BA mice had significantly increased mRNA expression of innate cytokines and miRNAs known to bind bile acid transporters/nuclear receptors (miRNAs -22-5p, -34a-5p, and -222-3p) and decreased mRNA expression of bile acid transporters and nuclear receptors. In vitro, TNF-α and IL-1ß decreased BSEP and CYP7A1 while increasing miRNA-34a-5p and miRNA 222-3p. LXR, SHP, CYP7A1, NTCP, and MRP2 were decreased by miRNA-34a-5p, whereas miRNA-222-3p decreased NTCP and MRP4. TNF-α and IL-1ß increased expression of miRNAs 34a-5p and 222-3p and these miRNAs then decrease expression of multiple bile acid transporters and nuclear receptors. CONCLUSIONS: Loss of bile acid transporters increases hepatotoxicity via bile acid retention. Therapeutic agents that increase bile acid transport or nuclear receptor functioning should be investigated in BA.
