Scientists and health professionals are exhaustively trying to contain the coronavirus disease 2019 (COVID-19) pandemic by elucidating viral invasion mechanisms, possible drugs to prevent viral ...infection/replication, and health cares to minimize individual exposure. Although neurological symptoms are being reported worldwide, neural acute and long-term consequences of SARS-CoV-2 are still unknown. COVID-19 complications are associated with exacerbated immunoinflammatory responses to SARS-CoV-2 invasion. In this scenario, pro-inflammatory factors are intensely released into the bloodstream, causing the so-called "cytokine storm". Both pro-inflammatory factors and viruses may cross the blood-brain barrier and enter the central nervous system, activating neuroinflammatory responses accompanied by hemorrhagic lesions and neuronal impairment, which are largely described processes in psychiatric disorders and neurodegenerative diseases. Therefore, SARS-CoV-2 infection could trigger and/or worse brain diseases. Moreover, patients with central nervous system disorders associated to neuroimmune activation (e.g. depression, Parkinson's and Alzheimer's disease) may present increased susceptibility to SARS-CoV-2 infection and/or achieve severe conditions. Elevated levels of extracellular ATP induced by SARS-CoV-2 infection may trigger hyperactivation of P2X7 receptors leading to NLRP3 inflammasome stimulation as a key mediator of neuroinvasion and consequent neuroinflammatory processes, as observed in psychiatric disorders and neurodegenerative diseases. In this context, P2X7 receptor antagonism could be a promising strategy to prevent or treat neurological complications in COVID-19 patients.
With increasing life expectancy, demands for dental tissue and whole-tooth regeneration are becoming more significant. Despite great progress in medicine, including regenerative therapies, the ...complex structure of dental tissues introduces several challenges to the field of regenerative dentistry. Interdisciplinary efforts from cellular biologists, material scientists, and clinical odontologists are being made to establish strategies and find the solutions for dental tissue regeneration and/or whole-tooth regeneration. In recent years, many significant discoveries were done regarding signaling pathways and factors shaping calcified tissue genesis, including those of tooth. Novel biocompatible scaffolds and polymer-based drug release systems are under development and may soon result in clinically applicable biomaterials with the potential to modulate signaling cascades involved in dental tissue genesis and regeneration. Approaches for whole-tooth regeneration utilizing adult stem cells, induced pluripotent stem cells, or tooth germ cells transplantation are emerging as promising alternatives to overcome existing in vitro tissue generation hurdles. In this interdisciplinary review, most recent advances in cellular signaling guiding dental tissue genesis, novel functionalized scaffolds and drug release material, various odontogenic cell sources, and methods for tooth regeneration are discussed thus providing a multi-faceted, up-to-date, and illustrative overview on the tooth regeneration matter, alongside hints for future directions in the challenging field of regenerative dentistry.
The Autism Spectrum Disorder (ASD) consists of a prevalent and heterogeneous group of neurodevelopmental diseases representing a severe burden to affected individuals and their caretakers. Despite ...substantial improvement towards understanding of ASD etiology and pathogenesis, as well as increased social awareness and more intensive research, no effective drugs have been successfully developed to resolve the main and most cumbersome ASD symptoms. Hence, finding better treatments, which may act as “disease-modifying” agents, and novel biomarkers for earlier ASD diagnosis and disease stage determination are needed. Diverse mutations of core components and consequent malfunctions of several cell signaling pathways have already been found in ASD by a series of experimental platforms, including genetic associations analyses and studies utilizing pre-clinical animal models and patient samples. These signaling cascades govern a broad range of neurological features such as neuronal development, neurotransmission, metabolism, and homeostasis, as well as immune regulation and inflammation. Here, we review the current knowledge on signaling pathways which are commonly disrupted in ASD and autism-related conditions. As such, we further propose ways to translate these findings into the development of genetic and biochemical clinical tests for early autism detection. Moreover, we highlight some putative druggable targets along these pathways, which, upon further research efforts, may evolve into novel therapeutic interventions for certain ASD conditions. Lastly, we also refer to the crosstalk among these major signaling cascades as well as their putative implications in therapeutics. Based on this collective information, we believe that a timely and accurate modulation of these prominent pathways may shape the neurodevelopment and neuro-immune regulation of homeostatic patterns and, hopefully, rescue some (if not all) ASD phenotypes.
Only a few microbial studies have conducted in IVF (in vitro fertilization), showing the high-variety bacterial contamination of IVF culture media to cause damage to or even loss of cultured oocytes ...and embryos. We aimed to determine the prevalence and counts of bacteria in IVF samples, and to associate them with clinical outcome.
The studied samples from 50 infertile couples included: raw (n = 48), processed (n = 49) and incubated (n = 50) sperm samples, and IVF culture media (n = 50). The full microbiome was analyzed by 454 pyrosequencing and quantitative analysis by real-time quantitative PCR. Descriptive statistics, t-, Mann-Whitney tests and Spearman's correlation were used for comparison of studied groups.
The study involved normozoospermic men. Normal vaginal microbiota was present in 72.0% of female partners, while intermediate microbiota and bacterial vaginosis were diagnosed in 12.0 and 16.0%, respectively. The decreasing bacterial loads were found in raw (35.5%), processed (12.0%) and sperm samples used for oocyte insemination (4.0%), and in 8.0% of IVF culture media. The most abundant genera of bacteria in native semen and IVF culture media were Lactobacillus, while in other samples Alphaproteobacteria prevailed. Staphylococcus sp. was found only in semen from patients with inflammation. Phylum Bacteroidetes was in negative correlation with sperm motility and Alphaproteobacteria with high-quality IVF embryos.
Our study demonstrates that IVF does not occur in a sterile environment. The prevalent bacteria include classes Bacilli in raw semen and IVF culture media, Clostridia in processed and Bacteroidia in sperm samples used for insemination. The presence of Staphylococcus sp. and Alphaproteobacteria associated with clinical outcomes, like sperm and embryo quality.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Parkinson’s disease is a neurodegenerative disorder characterized by decreased dopamine bioavailability in the substantia nigra and the striatum. Taking into account that ATP and its metabolites are ...intensely released in the 6-hydroxydopamine (6-OHDA) animal model of Parkinson’s disease, screening of purinergic receptor gene expression was performed. Effects of pharmacological P2Y6 or P2X7 receptor antagonism were studied in preventing or reversing hemiparkinsonian behavior and dopaminergic deficits in this animal model. P2X7 receptor antagonism with Brilliant Blue G at a dose of 75 mg/kg reestablished dopaminergic nigrostriatal pathway rats injured with 6-OHDA. Selective P2Y6 receptor antagonism by MRS2578 prevented dopaminergic neuron death in SH-SY5Y cells in vitro and in vivo in the substantia nigra of rats injured with 6-OHDA. Moreover, in vivo analysis showed that both treatments were accompanied by a reduction of microglial activation in the substantia nigra. Altogether, these data provide evidence that antagonism of P2X7 and P2Y6 receptors results in neuroregenerative and neuroprotective effects, respectively, possibly through modulation of neuroinflammatory responses.
Glioblastoma (GB) is the most aggressive primary tumor of central nervous system, where no efficient therapy has been found so far. This is due to high intra- and inter- tumor heterogeneity, fast ...invasion and the therapy-resistant subpopulation of GB stem cells and their plasticity. Tumor heterogeneity involves interactions among cancer cells and stromal cells, such as mesenchymal stem cells (MSCs), that are recruited into the tumor microenvironment and migrate to the tumor site. Here, we characterized the impact of kinin receptors on the interaction of MSCs with GB cells which is further enhanced by kinin receptor agonists. Interactions between GB cells and MSCs were studied in two- and three-dimensional co-cultures. Kinin receptor activity was modulated by selective agonists and antagonists to evaluate their influence on cell viability, cell-cell interactions, GB U87 cell invasiveness, and phenotype alterations. Tumor cell invasion was enhanced by the kinin-B2 receptor agonist bradykinin, while it was blocked by B2 receptor antagonists applied in U87 cells monoculture and in co-culture with MSCs. Kinin receptor inhibition correlated with enhanced direct U87/MSC interactions, such as heterotypic fusion, vesicle transfer and entosis. Furthermore, kinin receptor modulation influenced expression of F-actin expression and genes associated with epithelial-to-mesenchymal transition in U87 cells upon U87/MSCs co-cultures. Our data support ongoing investigations of kinin receptor inhibition as an adjuvant approach in GB therapy. MSC impacts on cancer progression need further investigation, as they may have a synergistic effect with kininergic receptor activation.
Display omitted
Bone tissue engineering is an ever-changing, rapidly evolving, and highly interdisciplinary field of study, where scientists try to mimic natural bone structure as closely as possible in order to ...facilitate bone healing. New insights from cell biology, specifically from mesenchymal stem cell differentiation and signaling, lead to new approaches in bone regeneration. Novel scaffold and drug release materials based on polysaccharides gain increasing attention due to their wide availability and good biocompatibility to be used as hydrogels and/or hybrid components for drug release and tissue engineering. This article reviews the current state of the art, recent developments, and future perspectives in polysaccharide-based systems used for bone regeneration.
Glioblastoma (GBM) is one of the most malignant and devastating brain tumors. The presence of highly therapy‐resistant GBM cell subpopulations within the tumor mass, rapid invasion into brain tissues ...and reciprocal interactions with stromal cells in the tumor microenvironment contributes to an inevitable fatal prognosis for the patients. We highlight the most recent evidence of GBM cell crosstalk with mesenchymal stem cells (MSCs), which occurs either by direct cell–cell interactions via gap junctions and microtubules or cell fusion. MSCs and GBM paracrine interactions are commonly observed and involve cytokine signaling, regulating MSC tropism toward GBM, their intra‐tumoral distribution, and immune system responses. MSC‐promoted effects depending on their cytokine and receptor expression patterns are considered critical for GBM progression. MSC origin, tumor heterogeneity and plasticity may also determine the outcome of such interactions. Kinins and kinin‐B1 and ‐B2 receptors play important roles in information flow between MSCs and GBM cells. Kinin‐B1 receptor activity favors tumor migration and fusion of MSCs and GBM cells. Flow and image (tissue) cytometry are powerful tools to investigate GBM cell and MSC crosstalk and are applied to analyze and characterize several other cancer types.
Determining breeding value by judging the exterior of poultry has always been a comprehensive issue. Breeding standards represent a detailed description of the appearance that characterizes the ideal ...representative of the given breed. They are listed in the current sample of poultry breeds. There is also a list of shortcomings – deviations from the ideal. This study briefly approaches the issue of assessing the external morphological features of selected breeds of chicken. The content is also focused on the evaluation of exterior signs – their advantages and deviations according to breeding standards in selected breeds of chicken that were judged at 9 exhibitions in 5 positions according to a valid Standards. In the study was used information from six breeds of chicken – Amrock, New Hampshire Red, Oravka, Plymouth Rock, Sussex and Wyandotte – in a total number of 719 individuals. Most exterior deficiencies were recorded in the first, third and fourth position. Among the most frequent exterior deficiencies in the first position - Breeding and sexual expression were lower weight, smaller body frame or weakly muscled body. In the third position – Body shape, the most shortcomings were noted insufficient body shape, poorly carried and feathered tail and non-standard posture. Shortcomings in fourth position - Feathers included poor colour or drawing, folds in the wings, sparse plumage on the tail, folds in the wings, sparse plumage and feathers on the legs. Thanks to these obtained data, in the future it is possible to avoid exterior defects, which appear more often in the monitored breeds
PDF
