1,721,095 research outputs found
Thrombosis and bleeding after COVID-19 vaccination: do differences in sex matter?
No full textGender medicine deals with differences in approach to diagnostic work-up and management according to gender. Although the issue is relevant in every field of medicine, it is often neglected. However, the recent SARS-CoV-2 pandemic has made consideration of gender even more urgent. In fact, available literature has suggested a higher number of deaths among infected men than in women and more side effects in women than in male recipients of certain anti-COVID-19 vaccines. This review examines sex-disaggregated data on thrombotic and bleeding events associated with vaccination against COVID-19. Thrombotic complications are by far more frequently reported than bleeding events after vaccination and are mostly observed in young women receiving viral-vectored vaccines. However, detailed data that could help better stratify the risk according to sex/gender are generally lacking. Likewise, overall bleeding complications and those associated with a specific vaccine are mainly reported as aggregated data, including thrombocytopenia that is reported to occur in the presence or absence of thrombotic complications. Such information is important as it underlines the need to differentiate between thrombocytopenia with and without thrombosis because management and prognosis differ according to the association of thrombotic events. Here, we highlight how the lack of disaggregated data has led to the publication of conflicting information about adverse events by sex in recipients of viral-vectored vaccines. Lastly, we examine the possible mechanisms underlying vaccine-associated thrombotic and bleeding complications according to sex/gender
Reply to comments of Carmona et al. to the article: Regenerative medicine for the treatment of musculoskeletal overuse injuries in competition horses
No full textIn a recently published study, we documented our experience
using platelet-rich plasma (PRP) and concentrated
bone marrow mononucleated cells (BMMNCs) for the
treatment of musculoskeletal injuries (ligament and tendon
overuse injuries) in competition horses refractory to other
therapies [1]. We evaluated number of cells and presence of
growth factors (GFs) injected, and performed follow-ups on
horses weekly, up to one year. The results of our study
showed a marked improvement in the degree of lameness,
with 84.6% of horses returning to competition, and a direct
correlation between number of platelets injected and
clinical outcome
Benefits of Applying Nanotechnologies to Hydrogels in Efficacy Tests in Osteoarthritis Models—A Systematic Review of Preclinical Studies
Full text linkOsteoarthritis (OA) is a severe musculoskeletal disease with an increasing incidence in the worldwide population. Recent research has focused on the development of innovative strategies to prevent articular cartilage damage and slow down OA progression, and nanotechnologies applied to hydrogels have gained particular interest. The aim of this systematic review is to investigate the state of the art on preclinical in vitro and in vivo efficacy studies applying nanotechnologies to hydrogels in OA models to elucidate the benefits of their applications. Three databases were consulted for eligible papers. The inclusion criteria were in vitro and in vivo preclinical studies, using OA cells or OA animal models, and testing hydrogels and nanoparticles (NPs) over the last ten years. Data extraction and quality assessment were performed. Eleven papers were included. In vitro studies evidenced that NP-gels do not impact on cell viability and do not cause inflammation in OA cell phenotypes. In vivo research on rodents showed that these treatments could increase drug retention in joints, reducing inflammation and preventing articular cartilage damage. Nanotechnologies in preclinical efficacy tests are still new and require extensive studies and technical hits to determine the efficacy, safety, fate, and localization of NPs for translation into an effective therapy for OA patients
Sex Specific Determinants in Osteoarthritis: A Systematic Review of Preclinical Studies
No full textOsteoarthritis (OA) is a highly prevalent joint disease that primarily affects about 10% of the world’s population over 60 years old. The purpose of this study is to systematically review the preclinical studies regarding sex differences in OA, with particular attention to the molecular aspect and gene expression, but also to the histopathological aspects. Three databases (PubMed, Scopus, and Web of Knowledge) were screened for eligible studies. In vitro and in vivo papers written in English, published in the last 11 years (2009–2020) were eligible. Participants were preclinical studies, including cell cultures and animal models of OA, evaluating sex differences. Independent extraction of articles and quality assessments were performed by two authors using predefined data fields and specific tools (Animals in Research Reporting In Vivo Experiments (ARRIVE) guideline and Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool). Twenty-three studies were included in the review: 4 in vitro studies, 18 in vivo studies, and 1 both in vitro and in vivo study. From in vitro works, sex differences were found in the gene expression of inflammatory molecules, hormonal receptors, and in responsiveness to hormonal stimulation. In vivo research showed a great heterogeneity of animal models mainly focused on the histopathological aspects rather than on the analysis of sex-related molecular mechanisms. This review highlights that many gaps in knowledge still exist; improvementsin the selection and reporting of animal models, the use of advanced in vitro models, and multiomics analyses might contribute to developing a personalized gender-based medicine
Estrogen deficiency does not decrease the in vitro osteogenic potential of rat adipose-derived mesenchymal stem cells.
No full textOsteoporosis due to estrogen deficiency is an increasing bone health issue worldwide: new strategies are being studied for regenerative medicine of bone pathologies in these patients. The most commonly used cells for tissue engineering therapy are the bone marrow mesenchymal stem cells (BMSCs), but they might be negatively affected by aging and estrogen deficiency. Besides the general advantages of adipose-derived mesenchymal stem cells (ADSCs) over BMSCs, ADSCs also seem to be less affected by aging than BMSCs, but in the literature, little is known about ADSCs in estrogen deficiency. The present study investigated the in vitro behavior of ADSCs, isolated from healthy (SHAM) and estrogen-deficient (OVX) rats. Phenotype, clonogenicity, viability, and osteogenic differentiation, at both cellular and molecular levels, were evaluated with or without osteogenic stimuli. Pro-inflammatory cytokines, growth factors, and adipogenic differentiation markers were also analyzed. There were no significant differences between OVX and SHAM ADSCs in some analyzed parameters. In addition, clonogenicity, osteopontin (Spp1) gene expression, alkaline phosphatase (ALP) activity at 2 weeks of culture, total collagen (COLL), osteocalcin (Bglap) gene expression and production, and matrix mineralization were significantly higher in OVX than in SHAM ADSCs. Besides the increase in some osteogenic markers, peroxisome proliferator-activated receptor gamma (Pparg) gene was also more expressed in OVX in osteogenic medium, with a concomitant estrogen receptor 1 (Esr1) gene expression decrease. These results underlined that ADSCs were not affected by estrogen deficiency in an osteogenic microenvironment
The influence of root surface distance to alveolar bone and periodontal ligament on periodontal wound healing
No full textPurpose: The purpose of this animal study was to perform a 3-dimensional micro-computed
tomography (micro-CT) analysis in order to investigate the influence of root surface distance
to the alveolar bone and the periodontal ligament on periodontal wound healing after a
guided tissue regeneration (GTR) procedure.
Methods: Three adult Sus scrofa domesticus specimens were used. The study sample included
6 teeth, corresponding to 2 third mandibular incisors from each animal. After coronectomy,
a circumferential bone defect was created in each tooth by means of calibrated piezoelectric
inserts. The experimental defects had depths of 3 mm, 5 mm, 7 mm, 9 mm, and 11 mm, with
a constant width of 2 mm. One tooth with no defect was used as a control. The defects were
covered with a bioresorbable membrane and protected with a flap. After 6 months, the animals
were euthanised and tissue blocks were harvested and preserved for micro-CT analysis.
Results: New alveolar bone was consistently present in all experimental defects. Signs of root
resorption were observed in all samples, with the extent of resorption directly correlated to
the vertical extent of the defect; the medial third of the root was the most commonly affected
area. Signs of ankylosis were recorded in the defects that were 3 mm and 7 mm in depth.
Density and other indicators of bone quality decreased with increasing defect depth.
Conclusions: After a GTR procedure, the periodontal ligament and the alveolar bone
appeared to compete in periodontal wound healing. Moreover, the observed decrease
in bone quality indicators suggests that intrabony defects beyond a critical size cannot
be regenerated. This finding may be relevant for the clinical application of periodontal
regeneration, since it implies that GTR has a dimensional limit
How exosomal platelet-derived miRNAs can lead to spontaneous osteoclastogenesis in osteoporosis: a new mechanistic viewpoint
Full text linkOsteoporosis is a chronic bone disease characterized by impaired bone remodeling and increased fracture risk. While classical mechanisms implicate estrogen deficiency, aging, and altered receptor activator of the nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) signaling, growing evidence supports a pivotal role of immune and inflammatory pathways in sustaining osteoclast-mediated bone resorption. A distinctive hallmark observed in osteoporotic patients is spontaneous osteoclastogenesis (SO), defined as the ability of mononuclear precursors to differentiate into osteoclasts even in the absence of exogenous stimuli such as RANKL or macrophage colony-stimulating factor (M-CSF), a process driven by an intrinsically primed in vivo microenvironment that includes platelets. We hypothesize that platelets may contribute to this priming not only through soluble mediators but also via the release of extracellular vesicles, particularly exosomes enriched in regulatory microRNAs (miRs). Within this framework, platelet-derived exosomal miRs (P-EXO-miRs) may orchestrate multiple intercellular interactions within the bone marrow microenvironment, modulating monocytes, macrophages, stromal and endothelial cells, as well as T and B lymphocytes. Specifically, miR-21, miR-223, miR-214, and miR-155 emerge as key candidates capable of regulating cytokine secretion, inflammatory signaling, and the RANKL/OPG balance, thereby promoting a pro-osteoclastogenic milieu. Network-based analysis using miRNet further supports the involvement of these miRs in pathways such as Hedgehog, Wnt, and actin cytoskeleton regulation, all relevant to osteoclast differentiation and function. Through these mechanisms, P-EXO-miRs may amplify chronic low-grade inflammation and facilitate spontaneous osteoclast differentiation and activity, ultimately contributing to bone loss in osteoporosis. Future investigations should aim to experimentally validate this platelet-bone axis, delineate the molecular targets of individual miRs, and explore their potential as circulating biomarkers or therapeutic targets. By unveiling this previously unrecognized role of platelet-derived miRs in SO, this hypothesis opens new perspectives for the understanding, early detection, and treatment of osteoporosis
Novel therapeutic targets in osteoarthritis: Narrative review on knock-out genes involved in disease development in mouse animal models
No full textOsteoarthritis (OA) can affect every joint, especially the knee. Given the complexity of this pathology, OA is difficult to treat with current therapies, which only relieve pain and inflammation and are not capable of restoring tissues once OA has started. Currently, researchers focus on finding a therapeutic strategy that may help to arrest disease progression.The present narrative review gives an overview of the genes involved in the development and progression of OA, assessing in vivo studies performed in knock-out mice affected by OA, to suggest new therapeutic strategies. The article search was performed on the PubMed database and www.webofknowledge.com website with the following keywords: "knee osteoarthritis" AND "knockout mice". The included studies were in English and published from 2005 to 2015. Additional papers were found within the references of the selected articles. In the 55 analyzed in vivo studies, genes mainly affected chondrocyte homeostasis, inflammatory processes, extracellular matrix and the relationship between obesity and OA. Genes are defined as inducing, preventing and not influencing OA. This review shows that joint homeostasis depends on a variety of genetic factors, and preventing or restoring the loss of a gene encoding for protective proteins, or inhibiting the expression of proteins that induce OA, might be a potential therapeutic approach. However, conclusions cannot be drawn because of the wide variability concerning the technique used for OA induction, the role of the genes, the method for tissue evaluations and the lack of assessments of all joint tissues
Protective effects of Polypodium leucotomos extract against UVB-induced damage in a model of reconstructed human epidermis
No full textBackground: Polypodium leucotomos (PL) exerts potent antioxidant, photo-protective, and immune-modulatory activities. A reconstructed human epidermis (RHE) (Episkin) is a suitable model for the evaluation of acute UV-induced cell damage. No data regarding the photo-protective action of PL in this model are available. Purpose: We evaluated the effects of PL on the prevention of UVB-induced cell damage assessing sunburn cells, CPD formation, p53, Ki-67, p21 expression, and epidermal growth factor (EGF) production. Materials & Methods: RHE was incubated in standard conditions. PL was topically applied at the concentration of 2 mg/cm2, immediately before UVB exposition. UVB exposition (300 mJ/cm2) was performed using a dedicated UVB lamp. Irradiated samples without PL and non-irradiated samples were used as positive and negative controls. Expression of p53, p21, and Ki-67 was evaluated with immune-histochemical methods. CPD were measured using a monoclonal antibody. Results: PL significantly reduced sunburned cells (-80%) in comparison with positive control. PL significantly prevented the increase in EGF production at tested times. PL significantly reduced the p53 (-80%), p21 (-84%), and Ki-67 (-48%) positive cells. Finally, PL prevented the formation of CPD (0% vs. 20% positive cells). Conclusion: In this model, PL has shown to prevent UVB cell damage, the upregulation of proliferating proteins, and fully blocking the formation of CPD
Role and translational implication of galectins in arthritis pathophysiology and treatment: A systematic literature review
No full textGalectins are members of the animal lectin family that bind to the β-galactoside-containing carbohydrate moieties of glycoconjugates. They seem to have an important role in the pathophysiology of several diseases, including arthritis. Osteoarthritis (OA) and rheumatoid arthritis (RA) are chronic conditions with few or no available therapies. In this context, galectins could provide a novel opportunity, but the precise role and mechanism of their involvement in arthritis are still not fully understood. This descriptive systematic literature review summarizes in vitro, in vivo, and clinical studies that analyzed and examined the role and mechanism of action of galectins in arthritis to highlight and clarify their possible translation implication. This review yielded promising evidence that individual galectins, in particular galectin-1, -3, and -9, could play positive or negative roles in the pathogenesis of arthritis, especially in RA and OA. It also emphasized the cell-dependent role of these galectins. This is particularly true for galectin-1, which was shown to have a protective anti-inflammatory role in RA, while it seemed to be associated with cartilage degeneration in OA. In summary, this review underlined that manipulation of certain galectins can suppress or aggravate disease symptoms in arthritis animal models, demonstrating the therapeutic potential of galectins for the treatment of RA and OA. Nevertheless, despite the fact that galectin therapy and therapies acting on galectin expression seem to be an interesting and important opportunity for research, we highlighted that further investigation is necessary to carefully evaluate their potential clinical implications in arthritis
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