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BACKGROUND: Different strategies for hand skin hygiene have been used to prevent the spread of SARS-CoV-2. However, frequent hand sanitization has been associated with skin damage. The present study aimed to evaluate hand hygiene habits during the COVID-19 pandemic and the effect of the repetitive use of soap or alcohol-based products on skin characteristics. METHODS: We conducted a survey regards hand hygiene habits acquired during the COVID-19 pandemic. Also, we performed cutometry in a cohort of individuals who cleansed their volar forearms every 30 min, during 4 h, using soap or alcohol-based products. RESULTS: We received 138 responses from people with medium-high educational level who reported a 2.5-time increase in the frequency of hand cleansing (p < 0.0001) that resulted in skin damage. An in vivo analysis of skin moisture and elasticity was also performed among 19 health workers and students. In general, skin moisture decreased with every cleansing, mainly after 2 h of washing with soap (p < 0.01), while skin elasticity only reduced after 4 h of treatment (p < 0.05). Alcohol-based solution or alcohol-based gel (70% ethanol, both) did not affect skin moisture or elasticity during testing. CONCLUSION: It is known that the excessive use of soap or alcohol-based products causes dermatological issues. The present study demonstrates that non-medicated soap significantly affects skin moisture and elasticity, probably because the soap removes the hydrolipidic protective barrier, favoring transepidermal water loss, where the lack of the appropriate stratum corneum hydration also affects skin elasticity, mainly associated with changes in epidermal structure.

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Ear pinna is a particular feature of mammals that shows several repair responses depending on age. Two millimeter hole made in the pinna of middle-aged female mice heals due to partial reconstitution of new tissues (limited regeneration), whereas a hole punched in the ear of young mice forms a scar tissue. In these studies, the injury is made in the center of the ear pinna, but little is known about the type of reparative response along the proximodistal polarity of the ear. This study evaluated the effect of pinna polarity, age, and sex in the ear hole-repairing response in Balb/c mice. Proximal injuries were repaired more efficiently by limited regeneration than wounds made in the middle region. Non-injured ear histological analysis revealed a higher presence of muscle, adipose tissue, cartilage, and larger blood vessels in the proximal ear area, which could influence ear hole closure by limited regeneration. To evaluate the healing response during ear growth, we punched a standard hole in the proximal area of the ear on postnatal day 21 and 8-month-old mice (adults). Thirty-five days after the wound, both groups reached the same wound closure, despite the greater proportional size of holes made in the younger mice. Ear growth also improved ear hole closure in male mice. These results suggest that ear growth accelerates hole closure, providing an example of enhanced regenerative abilities in growing structures. Finally, hole closure kinetics in the growing ear indicated an early re-differentiation phase exhibited at 14 days post-wound. In conclusion, ear topography and growth positively influenced the healing response to ear holes, making it a tractable model to study in mammals.

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In this work, we evaluated the direct effect of a dialkyl carbamoyl chloride (DACC)-coated dressing on Staphylococcus aureus adhesion and growth in vitro, as well as the indirect effect of the dressing on fibroblast and macrophage activity. S. aureus cultures were treated with the dressing or gauze in Müller-Hinton medium or serum-supplemented Dulbecco's modified Eagle medium. Bacterial growth and attachment were assessed through colony-forming units (CFU) and residual biomass analyses. Fibroblast and macrophage co-cultures were stimulated with filtered supernatants from the bacterial cultures treated with the DACC-coated dressing, following which tumor necrosis factor (TNF)-α/transforming growth factor (TGF)-ß1 expression and gelatinolytic activity were assessed by enzyme-linked immunosorbent assays (ELISA) and zymography, respectively. The DACC-coated dressing bound 1.8−6.1% of all of the bacteria in the culture. Dressing-treated cultures presented biofilm formation in the dressing (enabling mechanical removal), with limited formation outside of it (p < 0.001). Filtered supernatants of bacterial cultures treated with the DACC-coated dressing did not over-stimulate TNF-α or TGF-ß1 expression (p < 0.001) or increase gelatinolytic activity in eukaryotic cells, suggesting that bacterial cell integrity was maintained. Based on the above data, wound caregivers should consider the use of hydrophobic dressings as a first option for the management of acute or chronic wounds.

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Electrolyzed acid solutions produced by different methods have antiseptic properties due to the presence of chlorine and reactive oxygen species. Our aim was to determine whether a controlled-flow electrolyzed acid solution (CFEAS) has the ability to improve wound healing due to its antiseptic and antibiofilm properties. First, we demonstrated in vitro that Gram-negative and Gram-positive bacteria were susceptible to CFEAS, and the effect was partially sustained for 24 h, evidencing antibiofilm activity (p < 0.05, CFEAS-treated vs. controls). The partial cytotoxicity of CFEAS was mainly observed in macrophages after 6 h of treatment; meanwhile, fibroblasts resisted short-lived free radicals (p < 0.05, CFEAS treated vs. controls), perhaps through redox-regulating mechanisms. In addition, we observed that a single 24 h CFEAS treatment of subacute and chronic human wounds diminished the CFU/g of tissue by ten times (p < 0.05, before vs. after) and removed the biofilm that was adhered to the wound, as we observed via histology from transversal sections of biopsies obtained before and after CFEAS treatment. In conclusion, the electrolyzed acid solution, produced by a novel method that involves a controlled flow, preserves the antiseptic and antibiofilm properties observed in other, similar formulas, with the advantage of being safe for eukaryotic cells; meanwhile, the antibiofilm activity is sustained for 24 h, both in vitro and in vivo.

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ETHNOPHARMACOLOGICAL RELEVANCE: The bark of Amphipterygium adstringens Schiede ex Schltdl (Anacardiaceae), commonly known as 'cuachalalate' has been used in Mexican traditional medicine for the treatment of skin and oral lesions, gastric ulcers, and other conditions. The use as wound healing of the bark of this plant has been known since before the Spanish conquest of Mexico. Its uses are mentioned in the first writings of the Spanish in the 16th century. It is important to highlight that its use for wound healing treatment has no scientific previous reports. AIM OF THE STUDY: The objectives of this study were to determine the wound healing effect of the hydroalcoholic extract of the stem bark of Amphipterygium adstringens and its main metabolites, using a model of excision in the back of Wistar rats. To evaluate its antimicrobial effect against common bacteria that living on the skin of wounds and to evaluate its effect on angiogenesis. MATERIALS AND METHODS: The hydroalcoholic extract of cuachalalate (HAE, 10 mg/wound/day), the 3α-hydroxymasticadienoic acid (3 MA, 300 µg/wound/day), the masticadienoic acid (MA, 300 µg/wound/day), and a mixture of anacardic acids (ANA, 300 µg per wound) were tested in a murine excision model topically for 15 days, to evaluate their wound-healing effect. The results were reported in a wound closure percentage (n = 30 animals per treatment curve), using pirfenidone (PIR, 8% in vehicle) as a reference drug. In addition, histologic analysis was performed to evaluate the structure and quality of the scar. The effect on angiogenesis was assessed using the chick embryo chorioallantoic membrane (CAM) model (n = 6 eggs per treatment). The concentration evaluated for each treatment was 300 µg, using as proangiogenic reference drug the histamine (HIS, 5.6 µg) and as antiangiogenic drugs pirfenidone (9 µg) and acetylsalicylic acid (ASA, 9 µg). The antimicrobial test was performed against S. mutans, S. aureus, P. aeruginosa y E. coli using a minimum inhibitory concentration (MIC) assay. RESULTS: The 3α-hydroxymasticadienoic (3 MA) acid and the anacardic acids (ANA) improve the wound closure by approximates 30% (similar to pirfenidone) in comparison with the control-treated with the vehicle in the proliferative phase. On the other hand, the hydroalcoholic extract of cuachalalate (HAE) did not show an effect on the wound healing process. The histologic analysis demonstrated that the three main metabolites showed an improvement in the scar structure. According to the CAM results, it is probable that the main action mechanism of the 3α-hydroxymasticadienoic acid and the anacardic acids is related to their proangiogenic effect. In addition, ANA showed a modest antimicrobial effect. CONCLUSIONS: The 3α-hydroxymasticadienoic acid and anacardic acids showed a better tissue structure and reduced the time closure of the wound. In addition, the anacardic acids showed antimicrobial effects and both metabolites promote angiogenesis, suggesting that these effects may be related to their action mechanism. These metabolites of cuachalalate could be a good alternative for wound healing treatment.

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Grafting is the preferred treatment for severe skin burns. Frequently, allogeneic tissue is the only transient option for wound coverage, but their use risks damage to surrounding tissues. MicroRNAs have been associated with acute rejection of different tissues/organs. In this study, we analyzed the expression of miR-31, miR-155, and miR-221 and associate it with graft tolerance or rejection using a murine full-thickness skin transplantation model. Recipient animals for the syngeneic and allogeneic groups were BALB/c and C57BL/6 mice, respectively; donor tissues were obtained from BALB/c mice. After 7 days posttransplantation (DPT), the recipient skin and grafts in the syngeneic group maintained most of their structural characteristics and transforming growth factor (TGF)-ß1 and TGF-ß3 expression. Allografts were rejected early (Banff grades II and IV at 3 and 7 DPT, respectively), showing damage to the skin architecture and alteration of TGF-ß3 distribution. miRNAs skin expression changed in both mouse strains; miR-31 expression increased in the recipient skin of syngeneic grafts relative to that of allogeneic grafts at 3 and 7 DPT (P < .05 and P < .01, respectively); miR-221 expression increased in the same grafts at 7 DPT (P < .05). The only significant difference between donor tissues was observed for miR-155 expression at 7 DPT which was associated with necrotic tissue. Only miR-31 and miR-221 levels were increased in the blood of BALB/c mice that received syngeneic grafts after 7 DPT. Our data suggest that local and systemic miR-31 and miR-221 overexpression are associated with graft tolerance.

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Hepatocellular carcinoma expressing hepatobiliary progenitor markers, is considered of poor prognosis. By using a hepatocarcinogenesis model, laser capture microdissection, and RNA-Sequencing analysis, we identified an expression profile in GGT/KRT19-positive experimental tumors; 438 differentially expressed genes were found in early and late nodules along with increased collagen deposition. Dysregulated genes were involved in Fatty Acid Metabolism, RXR function, and Hepatic Stellate Cells Activation. Downregulation of Slc27a5, Acsl1, and Cyp2e1, demonstrated that Retinoid X Receptor α (RXRα) function is compromised in GGT/KRT19-positive nodules. Since RXRα controls NRF2 pathway activation, we determined the expression of NRF2 targeted genes; Akr1b8, Akr7a3, Gstp1, Abcc3, Ptgr1, and Txnrd1 were upregulated, indicating NRF2 pathway activation. A comparative analysis in human HCC showed that SLC27A5, ACSL1, CYP2E1, and RXRα gene expression is mutually exclusive with KRT19 gene expression. Our results indicate that the downregulation of Slc27a5, Acsl1, Rxrα, and Cyp2e1 genes is an early event within GGT/KRT19-positive HCC.

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The role of transforming growth factor ß TGFß/activin signaling in wound repair and regeneration is highly conserved in the animal kingdom. Various studies have shown that TGF-ß/activin signaling can either promote or inhibit different aspects of the regeneration process (i.e., proliferation, differentiation, and re-epithelialization). It has been demonstrated in several biological systems that some of the different cellular responses promoted by TGFß/activin signaling depend on the activation of Smad-dependent or Smad-independent signal transduction pathways. In the context of regeneration and wound healing, it has been shown that the type of R-Smad stimulated determines the different effects that can be obtained. However, neither the possible roles of Smad-independent pathways nor the interaction of the TGFß/activin pathway with other complex signaling networks involved in the regenerative process has been studied extensively. Here, we review the important aspects concerning the TGFß/activin signaling pathway in the regeneration process. We discuss data regarding the role of TGF-ß/activin in the most common animal regenerative models to demonstrate how this signaling promotes or inhibits regeneration, depending on the cellular context.

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BACKGROUND: Tissue replacement is among the most important challenges in biotechnology worldwide. SCOPE OF REVIEW: We aim to highlight the importance of the intricate feedback between rheological properties and materials science and cell biological parameters in order to obtain an efficient bioink design, supported by various practical examples. MAJOR CONCLUSIONS: Viscoelastic properties of bioink formulas, rheological properties, injection speed and printing nozzle diameter must be considered in bioink design. These properties are related to cell behavior and the survival rate during and after printing. Mechanosensing can strongly influence epigenetics to modify the final cell phenotype, which can affect the replacement tissue. GENERAL SIGNIFICANCE: In tissue engineering, biotechnologists must consider the biophysical properties and biological conditions of the materials used, as well as the material delivery mode (in a case or tissue) and maturation mode (curing or biomass), to ensure the development off appropriate materials mimicking the native tissue.

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Transforming growth factor beta (TGFß) signalling is involved in several aspects of regeneration in many organs and tissues of primitive vertebrates. It has been difficult to recognize the role of this signal in mammal regeneration due to the low ability of this animal class to reconstitute tissues. Nevertheless, ear-holes in middle-age female mice represent a model to study the limited epimorphic-like regeneration in mammals. Using this model, in this study we explored the possible participation of TGFß signalling in mammal regeneration. Positive pSmad3 cells, as well as TGFß1 and TGFß3 isoforms, were detected during the redifferentiation phase in the blastema-like structure. Daily administration of the inhibitor of the TGFß intracellular pathway, SB431542, during 7 days from the re-differentiation phase, resulted in a decreased level of pSmad3 accompanied by a transitory higher growth of the new tissue, larger cartilage nodules, and new muscle formation. These phenotypes were associated with a decrease in the number of α-SMA-positive cells and loose packing of collagen I. These results indicate that the modulation of the fibrosis mediated by TGFß signalling contributes to enhancing the differentiation of cartilage and muscle during limited ear-hole regeneration.

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