Fibroblast proliferation and migration in wound healing by phytochemicals: Evidence for a novel synergic outcome

Wound-healing is a dynamic skin reparative process that results in a sequence of events, including inflammation, proliferation, and migration of different cell types as fibroblasts. Fibroblasts play a crucial role in repairing processes, from the late inflammatory phase until the fully final epithelization of the injured tissue. Within this context, identifying tools able to implement cell proliferation and migration could improve tissue regeneration. Recently, plants species from all over the world are coming out as novel tools for therapeutic applications thanks to their phytochemicals, which have antioxidant properties and can promote wound healing. In this paper, we aimed at investigating antioxidant activity of waste extracts from different medicinal plants, endemic of the Mediterranean area, on fibroblast proliferation and wound healing. We determined the amount of total phenols and anti-oxidant activity by ABTS assay. We then evaluated the cytotoxicity of the compounds and the proliferative capabilities of fibroblasts by scratch assay. Our results showed that waste extracts retain antioxidant and regenerative properties, inducing tissue re-establishment after environmental stress exposure. Taken together, our findings suggest that waste material could be used in the future also in combinations to stimulate wound healing processes and antioxidant responses in damaged skin

381pdcomprehensive geriatric assessment cga for outcome prediction in elderly patients pts with glioblastoma gbm a mono institutional experience

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Isolating stem cells from skin: designing a novel highly efficient non-enzymatic approach

Stem cells are undifferentiated elements capable to acquire a specific cellular phenotype under the influence of specific stimuli, thus being involved in tissue integrity and maintenance. In the skin tissue self-renewal and wound healing after injury is a complex process, especially in adulthood, due to the aging process and the continuous exposure to damaging agents. The importance of stem cells in regenerative medicine is well known and defining or improving their isolation methods is therefore a primary and crucial step. In the present paper we present a novel method to isolate stem cells from human skin, including the involvement of a novel medium for the maintenance and expansion of in vitro cultures. The biopsies were mechanically digested and put in culture. The migrating cells were positive selected with magnetic cell sorting, characterized by flow-cytometry analysis, and viability detected by MTT assay. Cells exhibited a mesenchymal phenotype, as demonstrated by the positive acquirement of an osteogenic or adipogenic phenotype when cultured in specific conditioned media. Taken together our results disclose a novel method for culturing and expanding stem cells from skin and pave the way for future clinical applications in tissue regeneration

mismatch repair deficiency mmrd in glioma patients pts frequency and correlation with clinical histological and molecular characteristics

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Transapical off-pump echo-guided mitral valve repair with neochordae implantation mid-term outcomes

Background: The NeoChord echo-guided transapical beating heart repair is a promising early-stage minimally invasive surgical procedure for degenerative mitral valve (MV) regurgitation (DMR) correction. The technique has been improved since its inception following procedure standardization, patient selection optimization, and learning curve stabilization. We hereby present the mid-term clinical results through three years of our large single center experience. Methods: All consecutive patients with severe symptomatic DMR due to prolapse or flail of one or both mitral leaflets that underwent the NeoChord procedure between November 2013 and June 2019 were included. Patients were categorized according to MV anatomy; Type A isolated central posterior leaflet prolapse and/or flail, Type B posterior multi-segment prolapse and/or flail, Type C anterior and/or bi-leaflet prolapse or flail, Type D paracommissural prolapse and/or flail and/or significant leaflet and/or annular calcifications. Patients underwent clinical and echocardiographic follow-up at one, three, six, twelve months and yearly thereafter. Clinical outcomes and the composite primary endpoint (patient success) were defined according to Mitral Valve Academic Research Consortium (MVARC) criteria. Mitral regurgitation (MR) severity was graded as absent, mild, moderate and severe according to American Society of Echocardiography (ASE) and European Society of Cardiology (ESC) guidelines. Results: Two hundred and three patients were included; median follow-up was 24 months [interquartile range (IQR), 9–36]. Median age was 64 years (IQR, 54–74 years), median Society of Thoracic Surgeons (STS) Predicted Risk of Mortality (PROM) was 0.60% (IQR, 0.32–1.44%). There were 106 Type A patients (52.2%), 68 Type B (33.5%), 16 Type C (7.9%), and 13 Type D (6.4%). Kaplan-Meier estimate of survival was 99.0%±0.7% at one and two years and 94.0%±2.9% at three years. At one-year follow-up patient success was 91.2%±2.0% and 111 patients (74%) presented a residual MR mild or less (1+). At three-year follow-up patient success was 81.2%±3.8% and 32 patients (64%) had a residual MR mild or less (1+). Patient success was significantly different according to anatomical type (P=0.001). Echocardiographic analysis showed a significant acute left ventricle and left atrial reverse remodeling that was maintained up to three years. Conclusions: The NeoChord echo-guided transapical beating heart repair procedure demonstrated good clinical outcomes and echocardiographic results up to three-year follow-up

A subaliança Fraxino angustifoliae-Ulmenion minoris em Portugal continental.

A subaliança Fraxino angustifoliae-Ulmenion minoris (Populion albae, Populet alia albae, Salici purpureaePopuletea nigrae) reúne os bosques climácicos tempori higrófilos das zonas mais elevadas das margens dos rios - raramente inundadas - bem como de cabeceiras de linhas de água - onde o caudal não chega a ser permanente. Com base em inventários realizados desde 2004, são propostos dois novos sintáxones no âmbito desta subaliança : Hedero hibernicae Fraxinetum angustifoliae omphalodetosum nitidae e Clematido campanifloraeCeltidetum australis. Por fim, apresenta-se uma análise de agrupamento (cluster analysis) com todas as comunidades pertencentes a esta subaliança, com presença reconhecida em Portugal continental. Tal análise revelou que a sintaxonomia - actual e proposta - é consistente, discriminando claramente os sintáxones em causa

Smart nanofibers with natural extracts prevent senescence patterning in a dynamic cell culture model of human skin

Natural cosmetic products have recently re-emerged as a novel tool able to counteract skin aging and skin related damages. In addition, recently achieved progress in nanomedicine opens a novel approach yielding from combination of modern nanotechnology with traditional treatment for innovative pharmacotherapeutics. In the present study, we investigated the antiaging effect of a pretreatment with Myrtus communis natural extract combined with a polycaprolactone nanofibrous scaffold (NanoPCL-M) on skin cell populations exposed to UV. We set up a novel model of skin on a bioreactor mimicking a crosstalk between keratinocytes, stem cells and fibroblasts, as in skin. Beta-galactosidase assay, indicating the amount of senescent cells, and viability assay, revealed that fibroblasts and stem cells pretreated with NanoPCL-M and then exposed to UV are superimposable to control cells, untreated and unexposed to UV damage. On the other hand, cells only exposed to UV stress, without NanoPCL-M pretreatment, exhibited a significantly higher yield of senescent elements. Keratinocyte-based 3D structures appeared disjointed after UV-stress, as compared to NanoPCL-M pretreated samples. Gene expression analysis performed on different senescence associated genes, revealed the activation of a molecular program of rejuvenation in stem cells pretreated with NanoPCL-M and then exposed to UV. Altogether, our results highlight a future translational application of NanoPCL-M to prevent skin aging

Epigenetics, stem cells, and autophagy: Exploring a path involving miRNA

MiRNAs, a small family of non-coding RNA, are now emerging as regulators of stem cell pluripotency, differentiation, and autophagy, thus controlling stem cell behavior. Stem cells are undifferentiated elements capable to acquire specific phenotype under different kind of stimuli, being a main tool for regenerative medicine. Within this context, we have previously shown that stem cells isolated from Wharton jelly multipotent stem cells (WJ-MSCs) exhibit gender differences in the expression of the stemness related gene OCT4 and the epigenetic modulator gene DNA-Methyltransferase (DNMT1). Here, we further analyze this gender difference, evaluating adipogenic and osteogenic differentiation potential, autophagic process, and expression of miR-145, miR-148a, and miR-185 in WJ-MSCs derived from males and females. These miRNAs were selected since they are involved in OCT4 and DNMT1 gene expression, and in stem cell differentiation. Our results indicate a difference in the regulatory circuit involving miR-148a/DNMT1/OCT4 autophagy in male WJ-MSCs as compared to female cells. Moreover, no difference was detected in the expression of the two-differentiation regulating miRNA (miR-145 and miR-185). Taken together, our results highlight a different behavior of WJ-MSCs from males and females, disclosing the chance to better understand cellular processes as autophagy and stemness, usable for future clinical applications

COVID-19 Vaccinations: Perceptions and Behaviours in People with Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare genetic disease that causes recurrent respiratory infections. People with PCD may be at higher risk of severe coronavirus disease 2019 (COVID-19), and therefore vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important. We studied vaccination willingness, speed of vaccination uptake, side effects, and changes in social contact behaviour after vaccination in people with PCD. We used data from COVID-PCD, an international participatory cohort study. A COVID-19 vaccination questionnaire was emailed to participants in May 2021 and 423 participants from 31 countries replied (median age: 30 years, range 1–85 years; 261 (62%) female). Vaccination uptake and willingness were high, with 273 of 287 adults (96%) being vaccinated or willing to be in June 2021; only 4% were hesitant. The most common reason for hesitancy was fear of side effects, reported by 88%. Mild side effects were common, but no participant reported severe side effects. Half of the participants changed their social behaviour after vaccination by seeing friends and family more often. The high vaccination willingness in the study population might reflect the extraordinary effort taken by PCD support groups to inform people about COVID-19 vaccination. Clear and specific information and involvement of representatives is important for high vaccine uptake

ATG24 represses autophagy and differentiation and is essential for homeostasy of the flagellar pocket in trypanosoma brucei

We have previously identified homologs for nearly half of the approximately 30 known yeast Atg's in the genome database of the human sleeping sickness parasite Trypanosoma brucei. So far, only a few of these homologs have their role in autophagy experimentally confirmed. Among the candidates was the ortholog of Atg24 that is involved in pexophagy in yeast. In T. brucei, the peroxisome-like organelles named glycosomes harbor core metabolic processes, especially glycolysis. In the autotrophic yeast, autophagy is essential for adaptation to different nutritional environments by participating in the renewal of the peroxisome population. We hypothesized that autophagic turnover of the parasite's glycosomes plays a role in differentiation during its life cycle, which demands adaptation to different host environments and associated dramatic changes in nutritional conditions. We therefore characterized T. brucei ATG24, the T. brucei ortholog of yeast Atg24 and mammalian SNX4, and found it to have a regulatory role in autophagy and differentiation as well as endocytic trafficking. ATG24 partially localized on endocytic membranes where it was recruited via PI3-kinase III/VPS34. ATG24 silencing severely impaired receptor-mediated endocytosis of transferrin, but not adsorptive uptake of a lectin, and caused a major enlargement of the flagellar pocket. ATG24 silencing approximately doubled the number of autophagosomes, suggesting a role in repressing autophagy, and strongly accelerated differentiation, in accordance with a role of autophagy in parasite differentiation. Overexpression of the two isoforms of T. brucei ATG8 fused to GFP slowed down differentiation, possibly by a dominant-negative effect. This was overcome by ATG24 depletion, further supporting its regulatory role