Development of an amplicon-based sequencing approach in response to the global emergence of mpox.

The 2022 multicountry mpox outbreak concurrent with the ongoing Coronavirus Disease 2019 (COVID-19) pandemic further highlighted the need for genomic surveillance and rapid pathogen whole-genome sequencing. While metagenomic sequencing approaches have been used to sequence many of the early mpox infections, these methods are resource intensive and require samples with high viral DNA concentrations. Given the atypical clinical presentation of cases associated with the outbreak and uncertainty regarding viral load across both the course of infection and anatomical body sites, there was an urgent need for a more sensitive and broadly applicable sequencing approach. Highly multiplexed amplicon-based sequencing (PrimalSeq) was initially developed for sequencing of Zika virus, and later adapted as the main sequencing approach for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Here, we used PrimalScheme to develop a primer scheme for human monkeypox virus that can be used with many sequencing and bioinformatics pipelines implemented in public health laboratories during the COVID-19 pandemic. We sequenced clinical specimens that tested presumptively positive for human monkeypox virus with amplicon-based and metagenomic sequencing approaches. We found notably higher genome coverage across the virus genome, with minimal amplicon drop-outs, in using the amplicon-based sequencing approach, particularly in higher PCR cycle threshold (Ct) (lower DNA titer) samples. Further testing demonstrated that Ct value correlated with the number of sequencing reads and influenced the percent genome coverage. To maximize genome coverage when resources are limited, we recommend selecting samples with a PCR Ct below 31 Ct and generating 1 million sequencing reads per sample. To support national and international public health genomic surveillance efforts, we sent out primer pool aliquots to 10 laboratories across the United States, United Kingdom, Brazil, and Portugal. These public health laboratories successfully implemented the human monkeypox virus primer scheme in various amplicon sequencing workflows and with different sample types across a range of Ct values. Thus, we show that amplicon-based sequencing can provide a rapidly deployable, cost-effective, and flexible approach to pathogen whole-genome sequencing in response to newly emerging pathogens. Importantly, through the implementation of our primer scheme into existing SARS-CoV-2 workflows and across a range of sample types and sequencing platforms, we further demonstrate the potential of this approach for rapid outbreak response.

Effect of high irradiance and short exposure times on the depth of cure of six bulk-fill resin composites.

This study examined the effect of high irradiance and short exposure times on the depth of cure of six resin-based composites (RBCs). Bluephase PowerCure and the Valo X light-curing units (LCUs) were used to photocure bulk-fill RBCs for their recommended exposure times: Admira Fusion x-tra (AFX/20s), Aura Bulk Fill (ABF/20s), Filtek One Bulk Fill (FOB/20s), Opus Bulk Fill APS (OBF/30s), Tetric EvoCeram Bulk Fill (TEC/10s) and Tetric PowerFill (TPF/10s). In addition, all bulk-fill RBCs were tested for depth of cure with one short 3 s exposure time from the Bluephase PowerCure or the Valo X in the Xtra Power mode. The RBCs (n = 10 per RBC) were inserted into a 4 mm diameter metal mold and covered by a polyester strip before being photocured. After 24 h of storage, uncured RBC was scraped away to determine the depth of cure of the RBCs. None of the RBCs achieved a 4 mm depth of cure. The depth of cure of TEC and TPF was unaffected by the exposure times (recommended or short) when using the Valo X. The depth of cure of AFX/20s, AFX/Xtra Power, ABF/Xtra Power, FOB/Xtra Power, and OBF/30s RBCs was greater when using Valo X compared to the Bluephase PowerCure. It was concluded that short exposure times can reduce depth of cure and should only be used for some RBCs.

Subclinical choroidal involvement in Systemic Lupus Erythematosus.

PURPOSE: To assess the choroidal status of Systemic Lupus Erythematosus (SLE) patients using Optical Coherence Tomography (OCT) and OCT-Angiography. METHODS: SLE patients with disease duration < 10 years, no disease activity and no ocular involvement were recruited and cross-sectionally evaluated. A demographically similar cohort of healthy subjects was used for comparison. The main outcome is choroidal vascularity index (CVI). As secondary outcomes, choriocapillaris parameters and choroidal thickness (CT) were evaluated. RESULTS: Forty eyes of 40 subjects (20 SLE patients and 20 healthy subjects) were studied with a mean ± SD age of 36.7 ± 9.9 years. In the SLE group, the mean ± SD duration of disease was 7.35 ± 2.21 years. Increased CVI was found in the SLE group (p = 0.022). Considering the choriocapillaris, SLE patients presented a lower number (p = 0.037) and a smaller total area (p = 0.041) of signal voids. No differences between groups were found in CT. For SLE patients, CT at subfoveal, temporal and inferior locations presented a negative moderate correlation with disease duration. A strong correlation between choriocapillaris parameters and age was demonstrated for both groups. CONCLUSIONS: This study provides evidence of subclinical choroidal changes in adult SLE patients with inactive disease and no overt ocular manifestation. Increased CVI and fewer and smaller flow voids in choriocapillaris with normal CT suggest increased choroidal vascularity in SLE.

Diagnostic evaluation of institutions as a basis for designing the Brazilian maturity model of telehealth services.

BACKGROUND: The number and specificities of telehealth service units that expanded their services and diversified with the COVID-19 pandemic in Brazil need to be discovered. The objective of this manuscript is to present a methodology for the diagnostic evaluation of 19 telehealth units from different regions of the country for federal governmental decision-making. METHODS: A cross-sectional quantitative and qualitative study was carried out in the form of a census based on administrative records with an online survey and in-depth interviews with local telehealth managers. RESULTS: Despite the discontinuity of regular funding, the results point to a diversity of initiatives and advances. Citizenship, sustainability, security, and budget management are recurring themes in the maturity analysis of telehealth services after the advent of the pandemic. CONCLUSION: It is necessary for Brazil to build a resilient model of the maturity of telehealth services that contemplates the different regional scenarios.

Stool Glycoproteomics Signatures of Pre-Cancerous Lesions and Colorectal Cancer.

Colorectal cancer (CRC) screening relies primarily on stool analysis to identify occult blood. However, its sensitivity for detecting precancerous lesions is limited, requiring the development of new tools to improve CRC screening. Carcinogenesis involves significant alterations in mucosal epithelium glycocalyx that decisively contribute to disease progression. Building on this knowledge, we examined patient series comprehending premalignant lesions, colorectal tumors, and healthy controls for the T-antigen-a short-chain O-glycosylation of proteins considered a surrogate marker of malignancy in multiple solid cancers. We found the T-antigen in the secretions of dysplastic lesions as well as in cancer. In CRC, T-antigen expression was associated with the presence of distant metastases. In parallel, we analyzed a broad number of stools from individuals who underwent colonoscopy, which showed high T expressions in high-grade dysplasia and carcinomas. Employing mass spectrometry-based lectin-affinity enrichment, we identified a total of 262 proteins, 67% of which potentially exhibited altered glycosylation patterns associated with cancer and advanced pre-cancerous lesions. Also, we found that the stool (glyco)proteome of pre-cancerous lesions is enriched for protein species involved in key biological processes linked to humoral and innate immune responses. This study offers a thorough analysis of the stool glycoproteome, laying the groundwork for harnessing glycosylation alterations to improve non-invasive cancer detection.

Influence of new complete dentures on the touch perception threshold and quality of life of edentulous patients.

OBJECTIVE: To evaluate the touch perception threshold of the alveolar mucosa and quality of life of edentulous patients before (T0) and 30 days after (T1) the insertion of new complete dentures. BACKGROUND: Touch perception is important so that edentulous patients can detect the position of complete dentures in their mouth. MATERIALS AND METHODS: This study included 32 complete denture wearers with good oral and systemic health and no temporomandibular disorders for at least 5 years. At each time point (T0 and T1), two tests were performed (touch perception threshold and quality-of-life scale). The touch perception threshold (Von Frey or Semmes-Weinstein test) was assessed using nylon monofilaments on the regions of the alveolar mucosa of the maxilla and mandible. The Oral Health Impact Profile for edentulous individuals (OHIP-EDENT) was administered to evaluate oral health-related quality of life. RESULTS: In the maxilla and mandible, the touch perception thresholds for all regions of the alveolar mucosa were significantly lower at T1 than at T0. The OHIP-EDENT mean scores showed that the overall quality of life was significantly better at T1 (3.6) than at T0 (4.7), and a significant improvement in quality of life was observed in all domains of the OHIP-EDENT at T1. For touch perception threshold, effect sizes ranged from 0.4 to 0.8; and for quality of life, effect sizes ranged from 0.4 to 1.0. CONCLUSIONS: New complete dentures reduced the touch perception threshold of the alveolar mucosa of both edentulous arches and improved individuals' quality of life.

Comparative Effectiveness of COVID-19 Vaccines in Preventing Infections and Disease Progression from SARS-CoV-2 Omicron BA.5 and BA.2, Portugal.

We estimated comparative primary and booster vaccine effectiveness (VE) of SARS-CoV-2 Omicron BA.5 and BA.2 lineages against infection and disease progression. During April-June 2022, we implemented a case-case and cohort study and classified lineages using whole-genome sequencing or spike gene target failure. For the case-case study, we estimated the adjusted odds ratios (aORs) of vaccination using a logistic regression. For the cohort study, we estimated VE against disease progression using a penalized logistic regression. We observed no reduced VE for primary (aOR 1.07 [95% CI 0.93-1.23]) or booster (aOR 0.96 [95% CI 0.84-1.09]) vaccination against BA.5 infection. Among BA.5 case-patients, booster VE against progression to hospitalization was lower than that among BA.2 case-patients (VE 77% [95% CI 49%-90%] vs. VE 93% [95% CI 86%-97%]). Although booster vaccination is less effective against BA.5 than against BA.2, it offers substantial protection against progression from BA.5 infection to severe disease.

Antibacterial activity and physicochemical properties of a sealer containing copaiba oil.

This study aimed to evaluate the antimicrobial activity and physicochemical properties of a novel dual-cure endodontic sealer containing copaiba oil. The copaiba oil was obtained and characterized by gas chromatography (GC), and the minimum inhibitory concentration (MIC) was performed. The experimental sealers were formulated with copaiba oil concentrations of 0, 0.5, 1, and 2%, and the RealSeal™ (Sybron endo, Orange, USA) and AH Plus (Dentsply De Trey Gmbh, Konstanz, Germany) were used as the commercial references. The antimicrobial activity of the sealers was evaluated by the direct contact test for 1h and 24h. To evaluate the physicochemical properties of the sealers, the degree of conversion, setting time, film thickness, dimensional stability, and radiopacity tests were performed. The data were statistically analyzed by one-way ANOVA and Tukey's test (α = 0.05). Concerning the results, the sealers containing copaiba oil showed antimicrobial activity without harming the physicochemical properties.

The Role of Novel Digital Clinical Tools in the Screening or Diagnosis of Obstructive Sleep Apnea: Systematic Review.

BACKGROUND: Digital clinical tools are a new technology that can be used in the screening or diagnosis of obstructive sleep apnea (OSA), notwithstanding the crucial role of polysomnography, the gold standard. OBJECTIVE: This study aimed to identify, gather, and analyze the most accurate digital tools and smartphone-based health platforms used for OSA screening or diagnosis in the adult population. METHODS: We performed a comprehensive literature search of PubMed, Scopus, and Web of Science databases for studies evaluating the validity of digital tools in OSA screening or diagnosis until November 2022. The risk of bias was assessed using the Joanna Briggs Institute critical appraisal tool for diagnostic test accuracy studies. The sensitivity, specificity, and area under the curve (AUC) were used as discrimination measures. RESULTS: We retrieved 1714 articles, 41 (2.39%) of which were included in the study. From these 41 articles, we found 7 (17%) smartphone-based tools, 10 (24%) wearables, 11 (27%) bed or mattress sensors, 5 (12%) nasal airflow devices, and 8 (20%) other sensors that did not fit the previous categories. Only 8 (20%) of the 41 studies performed external validation of the developed tool. Of these, the highest reported values for AUC, sensitivity, and specificity were 0.99, 96%, and 92%, respectively, for a clinical cutoff of apnea-hypopnea index (AHI)≥30. These values correspond to a noncontact audio recorder that records sleep sounds, which are then analyzed by a deep learning technique that automatically detects sleep apnea events, calculates the AHI, and identifies OSA. Looking at the studies that only internally validated their models, the work that reported the highest accuracy measures showed AUC, sensitivity, and specificity values of 1.00, 100%, and 96%, respectively, for a clinical cutoff AHI≥30. It uses the Sonomat-a foam mattress that, aside from recording breath sounds, has pressure sensors that generate voltage when deformed, thus detecting respiratory movements, and uses it to classify OSA events. CONCLUSIONS: These clinical tools presented promising results with high discrimination measures (best results reached AUC>0.99). However, there is still a need for quality studies comparing the developed tools with the gold standard and validating them in external populations and other environments before they can be used in clinical settings. TRIAL REGISTRATION: PROSPERO CRD42023387748; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=387748.

MicroRNA Biomarkers as Promising Tools for Early Colorectal Cancer Screening-A Comprehensive Review.

Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide. Early detection of this neoplasia has proven to improve prognosis, resulting in a 90% increase in survival. However, available CRC screening methods have limitations, requiring the development of new tools. MicroRNA biomarkers have emerged as a powerful screening tool, as they are highly expressed in CRC patients and easily detectable in several biological samples. While microRNAs are extensively studied in blood samples, recent interest has now arisen in other samples, such as stool samples, where they can be combined with existing screening methods. Among the microRNAs described in the literature, microRNA-21-5p and microRNA-92a-3p and their cluster have demonstrated high potential for early CRC screening. Furthermore, the combination of multiple microRNAs has shown improved performance in CRC detection compared to individual microRNAs. This review aims to assess the available data in the literature on microRNAs as promising biomarkers for early CRC screening, explore their advantages and disadvantages, and discuss the optimal study characteristics for analyzing these biomarkers.

Genome-Scale Characterization of Mycobacterium abscessus Complex Isolates from Portugal.

The Mycobacterium abscessus complex (MABC) is an emerging, difficult to treat, multidrug-resistant nontuberculous mycobacteria responsible for a wide spectrum of infections and associated with an increasing number of cases worldwide. Dominant circulating clones (DCCs) of MABC have been genetically identified as groups of strains associated with higher prevalence, higher levels of antimicrobial resistance, and worse clinical outcomes. To date, little is known about the genomic characteristics of MABC species circulating in Portugal. Here, we examined the genetic diversity and antimicrobial resistance profiles of 30 MABC strains isolated between 2014 and 2022 in Portugal. The genetic diversity of circulating MABC strains was assessed through a gene-by-gene approach (wgMLST), allowing their subspecies differentiation and the classification of isolates into DCCs. Antimicrobial resistance profiles were defined using phenotypic, molecular, and genomic approaches. The majority of isolates were resistant to at least two antimicrobials, although a poor correlation between phenotype and genotype data was observed. Portuguese genomes were highly diverse, and data suggest the existence of MABC lineages with potential international circulation or cross-border transmission. This study highlights the genetic diversity and antimicrobial resistance profile of circulating MABC isolates in Portugal while representing the first step towards the implementation of a genomic-based surveillance system for MABC at the Portuguese NIH.

Clinical reproducibility of different centric relation recording techniques in edentulous individuals: An observational cross-sectional study.

PURPOSE: To assess the reproducibility of four different centric relation (CR) recording techniques, and time spent performing each technique in edentulous individuals. MATERIALS AND METHODS: Four techniques were assessed: extraoral gothic arch (EOGA) tracing, intraoral gothic arch (IOGA) tracing, deglutition (D), and frontal manipulation with tongue elevation (FMTE). Twelve subjects participated in the study; four technique records were performed on each volunteer by the same operator. Each record was repeated three times, in the same period of the day, with a 30 min interval between each technique. The reproducibility of each technique was assessed by the tri-dimensional displacement of the position of the condylar housing (mandible condyle) to the wall of the condylar guide (glenoid cavity) in the semi-adjustable articulator (anteroposterior, mediolateral, and superior-inferior). The time spent on each technique was timed in seconds (from the beginning of each technique until the wax occlusion fixation). The analysis of variance (ANOVA) and the Tukey test were performed for anteroposterior displacement (two-way) and for time spent on CT recording techniques (one-way) (α < 0.05). Regarding mediolateral and superior-inferior displacements, the nonparametric Kruskal-Wallis was performed for the comparison between recording methods, whereas the Mann-Whitney test was performed for the comparison between sides (α < 0.05). RESULTS: The factor recording technique interfered with the anteroposterior displacement (ANOVA: α < 0.001; F = 11.396). The technique D (right side: 3.78 ± 0.69 mm; left side: 3.45 ± 0.74 mm) showed a statistically significant difference compared to the other techniques (EOGA: right side: 3.00 ± 0.00 mm; left side: 3.00 ± 0.00 mm; FMTE: right side: 2.81 ± 0.52 mm; left side: 2.82 ± 0.79 mm; IOGA: right side: 2.90 ± 0.65 mm; left side: 3.12 ± 0.44 mm). The time spent on the recording technique influenced the results (ANOVA: α < 0.001; F = 21.118). The IOGA (340.40 ± 163.41 s) and EOGA (285.93 ± 133.84 s) required more time compared to the D (86.00 ± 34.33 s) and FMTE (101.33 ± 36.72 s) techniques. CONCLUSION: Graphic recordings showed better reproducibility and accuracy of the position of the centric relation.

Complete Denture - Border Molding Technique Using a Laboratory Condensation Silicone Putty: Review.

During the fabrication of a complete denture, functional impression is taken. Literature studies show that polydimethylsiloxane (condensation silicone) has not been reported by United States dental schools to perform border molding. Thus, the purpose of this article is to review the functional impression technique when border molding is performed with a laboratory condensation silicone putty.

Removable Partial Denture - Functional Impression Techniques: Review.

The objective of this article is to concisely review the main clinical techniques used to make the functional impression to manufacture a removable partial denture. Through this review, the dentist can develop his clinical knowledge.

Influence of thermal cycles and disinfection on the roughness, microhardness and color of PETG/TPU and PMMA.

BACKGROUND: Occlusal splints can protect teeth during bruxism, preventing tooth wear, as well as during sports activities, shielding them from impacts. OBJECTIVES: To verify the influence of thermal cycles and disinfection on the roughness, microhardness and color of polyethylene terephthalate glycol/thermoplastic polyurethane (PETG/TPU) and poly(methyl methacrylate) (PMMA). MATERIAL AND METHODS: Thirty-six PETG/TPU samples and 36 PMMA samples were prepared (ø10 mm × 3 mm). Six groups were created according to the material and the disinfection method used (n = 12 each): PETG/TPU (glister), PETG/TPU (hypochlorite), PETG/TPU (soap), PMMA (glister), PMMA (hypochlorite), and PMMA (soap). Roughness, Knoop microhardness and color evaluations were performed before the experiments (T1), after thermocycling (T2) and after disinfection (T3). Three-way repeated measures analysis of variance (ANOVA) and Tukey's test were used for statistical evaluations. RESULTS: For roughness and color, ANOVA showed statistical significance based on the interaction between thermal cycling, material and disinfectant factors. In terms of Knoop microhardness, ANOVA showed statistical significance based on the interaction between thermal cycling and material factors. CONCLUSIONS: Roughness results were clinically acceptable in all groups at all time points, except the PETG/TPU and PMMA groups disinfected with hypochlorite. Microhardness significantly increased for both materials after thermal cycling, and at all time points, the microhardness of PMMA was significantly higher than that of PETG/TPU. After thermal cycling, the color changes were clinically unacceptable in all groups.

Cytotoxicity of cleaning agents for ocular prostheses.

BACKGROUND: Polymethylmethacrylate (PMMA) is the most used material for the manufacturing of eye prostheses. OBJECTIVES: To investigate the cytotoxicity of different cleaning agents for ocular prostheses on human conjunctival cells. MATERIAL AND METHODS: Six groups of specimens were created (saline, soap, 4% chlorhexidine, hydrogen peroxide, 1% triclosan, and citronella oil). Three specimens were made for each disinfectant at each disinfection period (1, 7, 15, 30, 60, and 90 days), totaling 108 specimens. Thus, the specimens were disinfected, with different disinfectants, for different periods of time. After each disinfection process, the specimens were washed with sterile distilled water. A human conjunctival cell line was grown on the acrylic resin specimens and then cytotoxicity tests (MTT and Neutral Red (NR)) were performed. A negative control (untreated cell cultures) and positive control (Tween 20) were created. Two-way analysis of variance (ANOVA) and Bonferroni test were performed (p < 0.05). RESULTS: For the MTT and NR tests, when there was a significant difference between the disinfectant and negative control, the disinfectant generated a significant reduction in cell proliferation most of the time. CONCLUSIONS: All reductions in cell proliferation caused by the disinfectants were clinically acceptable. All disinfectants tested in this study were found to be non-cytotoxic to human conjunctival cells.

Prevalence of anophthalmia etiological factors in patients treated in a reference center: A retrospective study.

Background: Ocular prosthesis rehabilitation has an important social, psychological, esthetic, and functional role. Congenital factors, trauma, and tumors, among others, can cause anophthalmia, and it is essential to identify the etiology to guide its prevention and treatment. Methods: The aim of this study was to retrospectively investigate the records of patients treated from 2013 to 2020 by the Oral and Maxillofacial Prosthesis Group, aiming to identify the prevalence of patients with anophthalmia and the etiology of their anophthalmia. After approval by the Human Research Ethics Committee, two calibrated researchers evaluated 520 records, identifying those from patients with anophthalmia. The inclusion criteria were records with complete and legible information from patients with anophthalmia and a description of their etiology. Descriptive statistics were performed, and etiological factors were categorized into trauma, congenital cause, end-stage eye disease, and tumor. Spearman's correlation was performed to verify the relation between gender and anophthalmia etiology, with a 5% significance level. Seventy-two records were included in the study. Results: It was observed that 33.4% of patients were women and 66.6% were men. The etiologies were physical trauma (52.4%), tumor (21.8%), end-stage eye disease (16.6%), and congenital cause (9.2%), and there was no correlation between gender and these etiologies (p = .301). Conclusion: Most of the cases identified were of traumatic origin, which allows the establishment of preventive and educational measures to avoid new cases of anophthalmia.

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones.

Dienones are challenging building blocks in natural product synthesis due to their high reactivity and complex synthesis. Based on previous work and own initial results, a new stereospecific sequential hydrozirconation/Pd-catalyzed acylation of enynes with acyl chlorides towards conjugated (2E,4E)-dienones is reported. We investigated a number of substrates with different alkyl and aryl substituents in the one-pot reaction and showed that regardless of the substitution pattern, the reactions lead to the stereoselective formation (≥95% (2E,4E)) of the respective dienones under mild conditions. It was found that enynes with alkyl chains gave higher yields than the corresponding aryl-substituted analogues, whereas the variation of the acyl chlorides did not affect the reaction significantly. The synthetic application is demonstrated by formation of non-natural and natural dienone-containing terpenes such as ß-ionone which was available in 4 steps and 6% overall yield.

Screening for Inhibitors of YAP Nuclear Localization Identifies Aurora Kinase A as a Modulator of Lung Fibrosis.

Idiopathic pulmonary fibrosis is a progressive lung disease with limited therapeutic options that is characterized by pathological fibroblast activation and aberrant lung remodeling with scar formation. YAP (Yes-associated protein) is a transcriptional coactivator that mediates mechanical and biochemical signals controlling fibroblast activation. We previously identified HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors (statins) as YAP inhibitors based on a high-throughput small-molecule screen in primary human lung fibroblasts. Here we report that several Aurora kinase inhibitors were also identified from the top hits of this screen. MK-5108, a highly selective inhibitor for AURKA (Aurora kinase A), induced YAP phosphorylation and cytoplasmic retention and significantly reduced profibrotic gene expression in human lung fibroblasts. The inhibitory effect on YAP nuclear translocation and profibrotic gene expression is specific to inhibition of AURKA, but not Aurora kinase B or C, and is independent of the Hippo pathway kinases LATS1 and LATS2 (Large Tumor Suppressor 1 and 2). Further characterization of the effects of MK-5108 demonstrate that it inhibits YAP nuclear localization indirectly via effects on actin polymerization and TGFß (Transforming Growth Factor ß) signaling. In addition, MK-5108 treatment reduced lung collagen deposition in the bleomycin mouse model of pulmonary fibrosis. Our results reveal a novel role for AURKA in YAP-mediated profibrotic activity in fibroblasts and highlight the potential of small-molecule screens for YAP inhibitors for identification of novel agents with antifibrotic activity.

Effects of Dermatan Sulfate from Marine Invertebrate Styela plicata in the Wound Healing Pathway: A Natural Resource Applied to Regenerative Therapy.

Acute and chronic dermatological injuries need rapid tissue repair due to the susceptibility to infections. To effectively promote cutaneous wound recovery, it is essential to develop safe, low-cost, and affordable regenerative tools. Therefore, we aimed to identify the biological mechanisms involved in the wound healing properties of the glycosaminoglycan dermatan sulfate (DS), obtained from ascidian Styela plicata, a marine invertebrate, which in preliminary work from our group showed no toxicity and promoted a remarkable fibroblast proliferation and migration. In this study, 2,4-DS (50 µg/mL)-treated and control groups had the relative gene expression of 84 genes participating in the healing pathway evaluated. The results showed that 57% of the genes were overexpressed during treatment, 16% were underexpressed, and 9.52% were not detected. In silico analysis of metabolic interactions exhibited overexpression of genes related to: extracellular matrix organization, hemostasis, secretion of inflammatory mediators, and regulation of insulin-like growth factor transport and uptake. Furthermore, in C57BL/6 mice subjected to experimental wounds treated with 0.25% 2,4-DS, the histological parameters demonstrated a great capacity for vascular recovery. Additionally, this study confirmed that DS is a potent inducer of wound-healing cellular pathways and a promoter of neovascularization, being a natural ally in the tissue regeneration strategy.