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1.
Resveratrol Inhibits Wound Healing and Lens Fibrosis: A Putative Candidate for Posterior Capsule Opacification Prevention.
Smith, AJO, Eldred, JA, Wormstone, IM
Investigative ophthalmology & visual science. 2019;(12):3863-3877
Abstract
PURPOSE Posterior capsule opacification (PCO) is a common complication of cataract surgery. In addition to improved surgical methods and IOL designs, it is likely additional agents will be needed to improve patient outcomes. Presently no pharmacological agent is in clinical use to prevent PCO. Here we investigate the putative ability of resveratrol (RESV), a naturally occurring polyphenol, as a therapeutic agent. METHODS The human lens epithelial cell line FHL124, a human lens capsular bag model, and central anterior epithelium were used as experimental systems. Standard culture was in 5% fetal calf serum Eagle's minimum essential medium; 10 ng/mL transforming growth factor-β2 (TGFβ2) was used to induce fibrotic changes. A scratch wound assay was used to measure cell migration and the patch assay was used to assess matrix contraction by FHL124 cells. Protein expression was assessed by immunocytochemistry and Western blot and gene expression by quantitative RT-PCR. In capsular bags, cell growth across the posterior lens capsule, capsular wrinkling, and epithelial-to-mesenchymal transition were determined by image analysis. RESULTS In FHL124 cells, addition of 30 μM RESV significantly impeded cell migration in a wound-healing assay. RESV significantly inhibited TGFβ2-induced expression of the myofibroblast marker alpha-smooth muscle actin (α-SMA) at both the message and protein levels, as well as significantly inhibiting matrix contraction induced by TGFβ2. In human capsular bags, 30 μM RESV significantly inhibited cell growth. TGFβ2-induced α-SMA expression and capsular wrinkling were also significantly inhibited by RESV treatment. RESV significantly suppressed expression of TGFβ2-induced genes associated with fibrotic disease, including matrix metalloproteinase-2 in FHL124 cells, capsular bags, and central anterior epithelium. CONCLUSIONS RESV can counter PCO-related physiological events in two human lens model systems. RESV therefore has the potential to be used as a candidate agent for the prevention of PCO, which in turn could benefit millions of cataract patients.
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2.
Vonoprazan versus proton-pump inhibitors for healing gastroesophageal reflux disease: A systematic review.
Miyazaki, H, Igarashi, A, Takeuchi, T, Teng, L, Uda, A, Deguchi, H, Higuchi, K, Tango, T
Journal of gastroenterology and hepatology. 2019;(8):1316-1328
Abstract
BACKGROUND AND AIM Gastroesophageal reflux disease (GERD) is a common disease caused by reflux of gastric contents to the esophagus. Proton-pump inhibitors (PPIs) are recommended as a first-line therapy to treat GERD. Recently, a new potassium-competitive acid blocker, vonoprazan, was launched in Japan. We aimed to evaluate the comparative efficacy of vonoprazan and other PPIs in healing GERD. METHODS We used MEDLINE and the Cochrane Central Register of Controlled Trials to search the literature. Double-blind randomized controlled trials for PPIs and/or vonoprazan that were published in English or Japanese and assessed healing effects in adult GERD patients were included. To estimate the comparative efficacy of treatments, we performed a Bayesian network meta-analysis to assess the consistency assumption. RESULTS Of 4001 articles identified in the database, 42 studies were eligible. One study was hand-searched and added to the analysis. For the main analysis of healing effects at 8 weeks, odds ratios (ORs) of vonoprazan (20 mg daily) to esomeprazole (20 mg), rabeprazole (20 mg), lansoprazole (30 mg), and omeprazole (20 mg) were 2.29 (95% credible interval, 0.79-7.06), 3.94 (1.15-14.03), 2.40 (0.90-6.77), and 2.71 (0.98-7.90), respectively. Subgroup analysis for patients with severe esophagitis at baseline showed significantly higher ORs for vonoprazan versus most of the comparator PPIs. CONCLUSIONS This analysis shows that the GERD healing effect of vonoprazan is higher than that of rabeprazole (20 mg) but not higher than other PPIs. Subgroup analysis indicated that vonoprazan is more effective than most PPIs for patients with severe erosive esophagitis.
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3.
The Role of Vitamin A in Wound Healing.
Polcz, ME, Barbul, A
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2019;(5):695-700
Abstract
Vitamin A is an essential micronutrient that comes in multiple forms, including retinols, retinals, and retinoic acids. Dietary vitamin A is absorbed as retinol from preformed retinoids or as pro-vitamin A carotenoids that are converted into retinol in the enterocyte. These are then delivered to the liver for storage via chylomicrons and later released into the circulation and to its biologically active tissues bound to retinol-binding protein. Vitamin A is a crucial component of many important and diverse biological functions, including reproduction, embryological development, cellular differentiation, growth, immunity, and vision. Vitamin A functions mostly through nuclear retinoic acid receptors, retinoid X receptors, and peroxisome proliferator-activated receptors. Retinoids regulate the growth and differentiation of many cell types within skin, and its deficiency leads to abnormal epithelial keratinization. In wounded tissue, vitamin A stimulates epidermal turnover, increases the rate of re-epithelialization, and restores epithelial structure. Retinoids have the unique ability to reverse the inhibitory effects of anti-inflammatory steroids on wound healing. In addition to its role in the inflammatory phase of wound healing, retinoic acid has been demonstrated to enhance production of extracellular matrix components such as collagen type I and fibronectin, increase proliferation of keratinocytes and fibroblasts, and decrease levels of degrading matrix metalloproteinases.
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4.
Amino acids and wound healing in people with limb-threatening diabetic foot ulcers.
Hung, SY, Tsai, JS, Yeh, JT, Chen, KH, Lin, CN, Yang, HM, Lin, CW, Chen, HY, Huang, CH, Huang, YY
Journal of diabetes and its complications. 2019;(10):107403
Abstract
BACKGROUND Amino acids are associated with wound healing in traumatic wounds and burns, although their effects on healing in patients with diabetic foot ulcers (DFUs) are limited. This study aimed to evaluate and identify specific amino acids associated with healing outcomes of patients with DFUs. METHODS Sixty-two out of 85 patients who completed the in-hospital treatment for limb-threatening DFUs were enrolled. All ulcers had epithelialization without clinical evidence of infection at discharge. The patients and their families were instructed on foot-care techniques and committed to regular follow-up for 1 year. Baseline characteristics, PEDIS wound classification, laboratory data and serum amino acid levels were used to analyze their predictive power. RESULTS Fifty-seven patients completed the study in which 38 had healed and 19 had unhealed ulcers. The unhealed group had higher incidence of coronary artery disease and larger wound size. Most patients received endovascular therapy (81.6% healed group; 78.9% unhealed group) before enrollment. Following adjustments for clinical factors, the serum levels of arginine (326.4 μmol/L vs. 245.0 μmol/L, P = 0.045), isoleucine (166.7 μmol/L vs. 130.1 μmol/L, P = 0.019), leucine (325.8 μmol/L vs. 248.9 μmol/L, P = 0.039), and threonine (186.7 μmol/L vs. 152.0 μmol/L, P = 0.019) were significantly higher in the healed group. CONCLUSIONS The amino acids associated with wound healing in DFUs differ from those reported for traditional traumatic wounds. These findings affirm the necessity for future large-scaled studies for the application of these amino acids in DFU healing, either as prognostic predictors or supplemented regimens.
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5.
Maytenus macrocarpa (Ruiz & Pav.) Briq.: Phytochemistry and Pharmacological Activity.
Malaník, M, Treml, J, Rjašková, V, Tížková, K, Kaucká, P, Kokoška, L, Kubatka, P, Šmejkal, K
Molecules (Basel, Switzerland). 2019;(12)
Abstract
Maytenus macrocarpa (Celastraceae) is a tree native to Amazonia. Its roots, leaves, bark, and combinations of these are used in traditional medicine mainly to treat rheumatism and, to a lesser extent, to heal wounds and to combat bronchitis and diarrhea. To date, mainly triterpenes and dihydro-β-agarofuran sesquiterpenes were isolated from M. macrocarpa. Extracts and selected pure compounds isolated from the leaves, roots, and stem bark showed antibacterial, antiviral, antiparasitic, anti-inflammatory, and cytotoxic activities in vitro. The aim of this review is to summarize the available ethnobotanical, phytochemical, and pharmacological information about this traditional Amazonian medicinal tree, as well as to attract the attention of phytochemists and pharmacognosists to this potentially interesting source of ethnopharmaceuticals.
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6.
The Potential Role of Medicinal Plants in Bone Regeneration.
Barbalho, SM, Araújo, AC, Penteado Detregiachi, CR, Buchaim, DV, Guiguer, ÉL
Alternative therapies in health and medicine. 2019;(4):32-39
Abstract
BACKGROUND AND CONTEXT Natural healing of bone lesions once incomplete or delayed bone regeneration represents an important clinical issue and plants possess compounds that may enhance bone healing, and avoid bone losses. OBJECTIVE The aim of this review is to evaluate the potential role of medicinal plants in the bone regenaration. METHODS/DESIGN This review has included relevant studies available in MEDLINE-PubMed in the last three years that associated the role of plants in the bone regeneration. The descriptors used were "bone regeneration and plants" and "bone regeneration and medicinal plants". RESULTS We selected 59 articles, but only 15 studies dovetailed the study objectives of this review. These studies showed that plants have potential in increasing in the osseointegration once their components may downregulate biomarkers such as interleukin (IL)-1β, IL-6, IL-8, Tumor Necrosis Factor-α, Metalloproteinase 2, and 3. They may also upregulate mediators such as Vascular Endothelial Growth Factor, Transforming-Growing Factor-β1, Bone Morphogenetic Protein-2, osteocalcin, osteopontin, and type 1 collagen. The control in the production of these cytokines may help bone regeneration. Plant components such as curcumol, caffeic acid, resveratrol, luteolin, and many others may also be useful in bone health once may interfere in Nuclear Factor-κB and Mitogen Activated Protein Kinases, and may modulate Ca2+ signaling, inflammatory mediator genes, and inhibiting osteoclast-mediated bone resorption. CONCLUSION Many plants possess components that are effective in promoting bone regeneration and new pharmaceutical technology and pharmacological researchers should be performed in order to establish the dose and the appropriate delivery vehicle of administration of the plant or its compounds.
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7.
Sustained Ca2+ mobilizations: A quantitative approach to predict their importance in cell-cell communication and wound healing.
Lee, Y, Kim, MT, Rhodes, G, Sack, K, Son, SJ, Rich, CB, Kolachalama, VB, Gabel, CV, Trinkaus-Randall, V
PloS one. 2019;(4):e0213422
Abstract
Epithelial wound healing requires the coordination of cells to migrate as a unit over the basement membrane after injury. To understand the process of this coordinated movement, it is critical to study the dynamics of cell-cell communication. We developed a method to characterize the injury-induced sustained Ca2+ mobilizations that travel between cells for periods of time up to several hours. These events of communication are concentrated along the wound edge and are reduced in cells further away from the wound. Our goal was to delineate the role and contribution of these sustained mobilizations and using MATLAB analyses, we determined the probability of cell-cell communication events in both in vitro models and ex vivo organ culture models. We demonstrated that the injury response was complex and represented the activation of a number of receptors. In addition, we found that pannexin channels mediated the cell-cell communication and motility. Furthermore, the sustained Ca2+ mobilizations are associated with changes in cell morphology and motility during wound healing. The results demonstrate that both purinoreceptors and pannexins regulate the sustained Ca2+ mobilization necessary for cell-cell communication in wound healing.
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8.
Evaluation of the effect of honey on the healing of tooth extraction wounds in 4- to 9-year-old children.
Mokhtari, S, Sanati, I, Abdolahy, S, Hosseini, Z
Nigerian journal of clinical practice. 2019;(10):1328-1334
Abstract
OBJECTIVE The aim of the this study was to evaluate the effect of honey on the healing of tooth extraction wounds in children 4‒9 years of age. SUBJECTS AND METHODS In the present randomized clinical trial, 51 patients, 4‒9 years of age were selected randomly. All the subjects required extraction of one deciduous molar tooth. The subjects were randomly assigned to two groups. In group 1, after extraction of the tooth, the dentist used a cotton swab applicator to place a layer of honey on a piece of gauze moistened with normal saline solution (NSS) and placed it on the socket. In group 2, honey was not used; rather, NSS was applied. On days 3 and 7 after tooth extraction, the wound sizes were measured. RESULTS In both groups, the wound sizes decreased significantly on the third day compared with baseline and on the seventh day compared with the third day (P < 0.05). On the third and seventh days after tooth extraction, wound sizes in the honey group were significantly lower than those in the NSS group (P < 0.05). CONCLUSION Honey resulted in a decrease in wound sizes and faster healing after extraction of teeth in children. Therefore, use of honey can be recommended after minor surgeries in the oral cavity.
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9.
The impact of stress on epidermal barrier function: an evidence-based review.
Maarouf, M, Maarouf, CL, Yosipovitch, G, Shi, VY
The British journal of dermatology. 2019;(6):1129-1137
Abstract
BACKGROUND The epidermal barrier functions to limit skin infection and inflammation by inhibiting irritant and immunogen invasion. Abundant evidence suggests that psychological stress stemming from crowding, isolation, nicotine smoking, insomnia, mental arithmetic tasks, physical pain, real-life stressors (examinations and marital strain) and lack of positive personality traits may impart both acute and chronic epidermal dysfunction. OBJECTIVES To review the relationship between stress and epidermal barrier dysfunction. METHODS A review of the PubMed and Embase databases was conducted to identify all English-language case-control, cross-sectional and randomized control trials that have reported the effect of stress on epidermal barrier function. The authors' conclusions are based on the available evidence from 21 studies that met the inclusion and exclusion criteria. RESULTS Psychological stressors upregulate the hypothalamic-pituitary-adrenal axis to stimulate local and systemic stress hormone production. This ultimately leads to aberrant barrier dysfunction, characterized by decreased epidermal lipid and structural protein production, decreased stratum corneum hydration and increased transepidermal water loss. CONCLUSIONS This evidence-based review explores the adverse effects of psychological stressors on epidermal barrier function. Future investigations using more real-life stressors are needed to elucidate further their impact on skin physiology and identify practical stress-relieving therapies that minimize and restore epidermal barrier dysfunction, particularly in at-risk populations. What's already known about this topic? The literature reports the negative effect of stress on prolonged wound healing. Less is known about the relationship between stress and epidermal barrier dysfunction, a chronic, superficial wound involving the upper epidermal layers. What does this study add? Psychological stressors impact epidermal barrier function by activating the hypothalamic-pituitary-adrenal axis to stimulate local and systemic stress hormone production. Stress hormones negatively affect the epidermal barrier by decreasing epidermal lipids and structural proteins, decreasing stratum corneum hydration and increasing transepidermal water loss. Identification of such stressors can promote stress-avoidance and stress-reduction behaviours that protect epidermal barrier function and prevent certain dermatological conditions.
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10.
Plantar Ulcers and Neuropathic Arthropathies: Associated Diseases, Polyneuropathy Correlates, and Risk Covariates.
Andrews, KL, Dyck, PJ, Kavros, SJ, Vella, A, Kazamel, M, Clark, V, Litchy, WJ, Dyck, PJB, Lodermeier, KA, Davies, JL, et al
Advances in skin & wound care. 2019;(4):168-175
Abstract
OBJECTIVE To evaluate the associated diseases, polyneuropathy correlates, and risk covariates of neuropathic plantar ulcers (PUs) and neuropathic arthropathies (NAs). DESIGN The authors conducted a retrospective, observational study over 3.5 years of 69 patients with neuropathy, NA, or PU seen in a wound clinic who also had a comprehensive neurologic evaluation and neurophysiologic testing. Comparisons were made to a population representative cohort of patients with diabetes mellitus (DM; n = 259). RESULTS Of the 69 wound clinic patients, 32 had PUs, 14 had NAs, and 23 had both. Of the 61 adequately assessed patients, 37 (61%) had DM, 22 (36%) had no known associated disease, and 2 (3%) had hereditary sensory and autonomic neuropathy. Of the 37 patients with DM, 35 had distal polyneuropathy, and 2 did not. In 22 patients with chronic idiopathic axonal polyneuropathy, 20 had distal polyneuropathy. CONCLUSIONS Although DM was the disease most commonly associated with PUs and NAs, chronic hyperglycemia may not have been the major underlying risk factor. The major risk covariates are sensation loss from polyneuropathy, old age, obesity, repetitive foot injury, and inadequate foot care or treatment. Physicians and other healthcare providers can help by identifying patients at risk and instituting measures such as adequate foot care to decrease these risks.