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Pulmonary fibrosis (PF), the end point of interstitial lung diseases, is characterized by myofibroblast over differentiation and excessive extracellular matrix accumulation, leading to progressive organ dysfunction and usually a terminal outcome. Studies have shown that umbilical cord-derived mesenchymal stromal cells (uMSCs) could alleviate PF; however, the underlying mechanism remains to be elucidated.
The therapeutic effects of uMSC-derived extracellular vesicles (uMSC-EVs) on PF were evaluated using bleomycin (BLM)-induced mouse models. Then, the role and mechanism of uMSC-EVs in inhibiting myofibroblast differentiation were investigated in vivo and in vitro.
Treatment with uMSC-EVs alleviated the PF and enhanced the proliferation of alveolar epithelial cells in BLM-induced mice, thus improved the life quality, including the survival rate, body weight, fibrosis degree, and myofibroblast over differentiation of lung tissue. Moreover, these effects of uMSC-EVs on PF are likely achieved by inhibiting the transforming growth factor-β (TGF-β) signaling pathway, evidenced by decreased expression levels of TGF-β2 and TGF-βR2. Using mimics of uMSC-EV-specific miRNAs, we found that miR-21 and miR-23, which are highly enriched in uMSC-EVs, played a critical role in inhibiting TGF-β2 and TGF-βR2, respectively.
The effects of uMSCs on PF alleviation are likely achieved via EVs, which reveals a new role of uMSC-EV-derived miRNAs, opening a novel strategy for PF treatment in the clinical setting.
The effects of uMSCs on PF alleviation are likely achieved via EVs, which reveals a new role of uMSC-EV-derived miRNAs, opening a novel strategy for PF treatment in the clinical setting.
Mutations in the DMD gene encoding dystrophin-a critical structural element in muscle cells-cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD.
In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46-54. We compared this approach with other DMD rescue strategies by using DMD patient-derived primary muscle-derived stem cells (DMD-MDSCs). Furthermore, a patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors.
Results demonstrated that the large-scale excision of mutant DMD exons showed high efficiency in restoring dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cas12a)-mediated genome editing could correct DMD mutation with the same efficiency as CRISPR-associated protein 9 (Cas9). In addition, more than 10% human DMD muscle fibers expressed dystrophin in the PDX DMD mouse model after treated by the large-scale excision strategies. The restored dystrophin in vivo was functional as demonstrated by the expression of the dystrophin glycoprotein complex member β-dystroglycan.
We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. This study demonstrated an approach for the application of gene therapy to other genetic diseases.
We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. selleck chemical This study demonstrated an approach for the application of gene therapy to other genetic diseases.
Coronary artery disease (CAD) is the leading cause of death worldwide. In this study, we aimed to explore whether some genetic variants of the human IDOL gene were associated with CAD among Chinese population in Xinjiang.
We designed two independent case-control studies. The first one included in the Han population (448 CAD patients and 343 controls), and the second one is the Uygur population (304 CAD patients and 318 controls). We genotyped three SNPs (rs2072783, rs2205796, and rs909562) of the IDOL gene.
Our results revealed that, in the Han female subjects, for rs2205796, the distribution of alleles, dominant model (TT vs. GG + GT) and the additive model (GG + TT vs. GT) showed significant differences between CAD patients and the control subjects (P = 0.048, P = 0.014, and P = 0.032, respectively).
The rs2205796 polymorphism of the IDOL gene is associated with CAD in the Chinese Han female population in Xinjiang, China.
The rs2205796 polymorphism of the IDOL gene is associated with CAD in the Chinese Han female population in Xinjiang, China.
Cystic echinococcosis (CE) is a disease caused by the larval stage of Echinococcus granulosussensu lato (s.l.). The treatment of CE mainly relies on the use of benzimidazoles, which can commonly cause adverse side effects. Therefore, more efficient treatment options are needed. Drug repurposing is a useful approach for advancing drug development. We have evaluated the in vitro protoscolicidal effects of tropisetron and granisetron in E. granulosussensu stricto (s.s.) and assessed the expression of the calcineurin (CaN) and calmodulin (CaM) genes, both of which have been linked to cellular signaling activities and thus are potentially promising targets for the development of drugs.
Protoscoleces (PSC) of E. granulosus (s.s.) (genotype G1) obtained from sheep hepatic hydatid cysts were exposed to tropisetron and granisetron at concentrations of 50, 150 and 250 µM for various periods of time up to 10 days. Cyclosporine A (CsA) and albendazole sulfoxide were used for comparison. Changes in the morphology of Pacy than granisetron against E. granulosus (s.s.) PSC, which is probably due to the different mechanisms of action of the two drugs. The concentration-dependent effect of tropisetron on calcineurin gene expression might reflect its dual functions, which should stimulate future research into its mechanism of action and evaluation of its potential therapeutical effect in the treatment of CE.
Tropisetron exhibited a higher efficacy than granisetron against E. granulosus (s.s.) PSC, which is probably due to the different mechanisms of action of the two drugs. The concentration-dependent effect of tropisetron on calcineurin gene expression might reflect its dual functions, which should stimulate future research into its mechanism of action and evaluation of its potential therapeutical effect in the treatment of CE.
In the early days of neurosurgery, extradural haemorrhages (EDHs) contributed to a high mortality rate after craniotomies. Almost a century ago, Walter Dandy reported dural tenting sutures as an effective way to prevent postoperative EDH. Over time, his technique gained in popularity and significance to finally become a neurosurgical standard. Yet, several retrospective reports and one prospective report have questioned the ongoing need for dural tenting sutures. Dandy's explanation that the haemostasis observed under hypotensive conditions is deceiving and eventually causes EDH may be obsolete. Today, proper intra- and postoperative care, including maintenance of normovolemia and normotension and the use of modern haemostatic agents, may be sufficient for effective haemostasis. Thus, there is a fundamental need to evaluate the necessity of dural tenting sutures in a solid, unbiased, evidence-based manner.
This study is designed as a randomised, multicentre, double-blinded, controlled interventional trialittee of the Medical University of Warsaw approved the study protocol (KB/106/2018). The trial is registered at http//www.clinicaltrials.gov ( NCT03658941 ) on September 6, 2018. The findings of this trial will be submitted to a peer-reviewed neurosurgical journal. Abstracts will be submitted to relevant national and international conferences.
Protocol version and date version 1.5, 14.01.2020 First recruitment September 7, 2018 Estimated recruitment completion September 1, 2021.
Protocol version and date version 1.5, 14.01.2020 First recruitment September 7, 2018 Estimated recruitment completion September 1, 2021.
Several essential factors have played a crucial role in the spreading mechanism of COVID-19 (Coronavirus disease 2019) in the human population. These factors include undetected cases, asymptomatic cases, and several non-pharmaceutical interventions. Because of the rapid spread of COVID-19 worldwide, understanding the significance of these factors is crucial in determining whether COVID-19 will be eradicated or persist in the population. Hence, in this study, we establish a new mathematical model to predict the spread of COVID-19 considering mentioned factors.
Infection detection and vaccination have the potential to eradicate COVID-19 from Jakarta. From the sensitivity analysis, we find that rapid testing is crucial in reducing the basic reproduction number when COVID-19 is endemic in the population rather than contact trace. Furthermore, our results indicate that a vaccination strategy has the potential to relax social distancing rules, while maintaining the basic reproduction number at the minimum possible, and also eradicate COVID-19 from the population with a higher vaccination rate. In conclusion, our model proposed a mathematical model that can be used by Jakarta's government to relax social distancing policy by relying on future COVID-19 vaccine potential.
Infection detection and vaccination have the potential to eradicate COVID-19 from Jakarta. From the sensitivity analysis, we find that rapid testing is crucial in reducing the basic reproduction number when COVID-19 is endemic in the population rather than contact trace. Furthermore, our results indicate that a vaccination strategy has the potential to relax social distancing rules, while maintaining the basic reproduction number at the minimum possible, and also eradicate COVID-19 from the population with a higher vaccination rate. In conclusion, our model proposed a mathematical model that can be used by Jakarta's government to relax social distancing policy by relying on future COVID-19 vaccine potential.
Free-living and symbiotic chemosynthetic microbial communities support primary production and higher trophic levels in deep-sea hydrothermal vents. The shrimp Rimicaris exoculata, which dominates animal communities along the Mid-Atlantic Ridge, houses a complex bacterial community in its enlarged cephalothorax. The dominant bacteria present are from the taxonomic groups Campylobacteria, Desulfobulbia (formerly Deltaproteobacteria), Alphaproteobacteria, Gammaproteobacteria, and some recently discovered iron oxyhydroxide-coated Zetaproteobacteria. This epibiotic consortium uses iron, sulfide, methane, and hydrogen as energy sources. Here, we generated shotgun metagenomes from Rimicaris exoculata cephalothoracic epibiotic communities to reconstruct and investigate symbiotic genomes. We collected specimens from three geochemically contrasted vent fields, TAG, Rainbow, and Snake Pit, to unravel the specificity, variability, and adaptation of Rimicaris-microbe associations.
Our data enabled us to reconstruct 49 metagenome-assembled genomes (MAGs) from the TAG and Rainbow vent fields, including 16 with more than 90% completion and less than 5% contamination based on single copy core genes.
Homepage: https://www.selleckchem.com/products/cc-930.html
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