Airway basal cells from human-induced pluripotent stem cells: a new frontier in cystic fibrosis research

Human-induced airway basal cells (hiBCs) derived from human-induced pluripotent stem cells (hiPSCs) offer a promising cell model for studying lung diseases, regenerative medicine, and developing new gene therapy methods. We analyzed existing differentiation protocols and proposed our own protocol for obtaining hiBCs, which involves step-by-step differentiation of hiPSCs into definitive endoderm, anterior foregut endoderm, NKX2.1+ lung progenitors, and cultivation on basal cell medium with subsequent cell sorting using the surface marker CD271 (NGFR). We derived hiBCs from two healthy cell lines and three cell lines with cystic fibrosis (CF). The obtained hiBCs, expressing basal cell markers (NGFR, KRT5, and TP63), could differentiate into lung organoids (LOs). We demonstrated that LOs derived from hiBCs can assess cystic fibrosis transmembrane conductance regulator (CFTR) channel function using the forskolin-induced swelling (FIS) assay. We also carried out non-viral (electroporation) and viral (recombinant adeno-associated virus (rAAV)) serotypes 6 and 9 and recombinant adenovirus (rAdV) serotype 5 transgene delivery to hiBCs and showed that rAAV serotype 6 is most effective against hiBCs, potentially applicable for gene therapy research

Impact of globalization on the development of commerce

Globalization, the transition to an information society - modern processes of social development, due to a number of factors: the structure of social reproduction of countries, the level of economic development of countries, the availability of natural resources, the peculiarities of the internal market, etc. Globalization and the increasingly active use of digital technologies are affecting changes in the country's internal trade, increasing the share of electronic commerce in its composition. Electronic commerce predetermines the development of channels of distribution of goods and services different from traditional channels, and the applied business processes make it possible to discover and apply existing reserves and previously unused potential opportunities in economic activity in order to increase not only the income received, but also provide goods to remote (and small) populations. points

Airway and Lung Organoids from Human-Induced Pluripotent Stem Cells Can Be Used to Assess CFTR Conductance

Airway and lung organoids derived from human-induced pluripotent stem cells (hiPSCs) are current models for personalized drug screening, cell–cell interaction studies, and lung disease research. We analyzed the existing differentiation protocols and identified the optimal conditions for obtaining organoids. In this article, we describe a step-by-step protocol for differentiating hiPSCs into airway and lung organoids. We obtained airway and lung organoids from a healthy donor and from five donors with cystic fibrosis. Analysis of the cellular composition of airway and lung organoids showed that airway organoids contain proximal lung epithelial cells, while lung organoids contain both proximal and distal lung epithelial cells. Forskolin-induced swelling of organoids derived from a healthy donor showed that lung organoids, as well as airway organoids, contain functional epithelial cells and swell after 24 h exposure to forskolin, which makes it a suitable model for analyzing the cystic fibrosis transmembrane conductance regulator (CFTR) channel conductance in vitro. Thus, our results demonstrate the feasibility of generating and characterizing airway and lung organoids from hiPSCs, which can be used for a variety of future applications

Airway and Lung Organoids from Human-Induced Pluripotent Stem Cells Can Be Used to Assess CFTR Conductance

Airway and lung organoids derived from human-induced pluripotent stem cells (hiPSCs) are current models for personalized drug screening, cell–cell interaction studies, and lung disease research. We analyzed the existing differentiation protocols and identified the optimal conditions for obtaining organoids. In this article, we describe a step-by-step protocol for differentiating hiPSCs into airway and lung organoids. We obtained airway and lung organoids from a healthy donor and from five donors with cystic fibrosis. Analysis of the cellular composition of airway and lung organoids showed that airway organoids contain proximal lung epithelial cells, while lung organoids contain both proximal and distal lung epithelial cells. Forskolin-induced swelling of organoids derived from a healthy donor showed that lung organoids, as well as airway organoids, contain functional epithelial cells and swell after 24 h exposure to forskolin, which makes it a suitable model for analyzing the cystic fibrosis transmembrane conductance regulator (CFTR) channel conductance in vitro. Thus, our results demonstrate the feasibility of generating and characterizing airway and lung organoids from hiPSCs, which can be used for a variety of future applications

Effects of oral ATP supplementation on anaerobic power and muscular strength

Purpose: We examined 14 d of oral adenosine 5′-triphosphate (ATP) supplementation on indices of anaerobic capacity and muscular strength. Methods: Twenty-seven healthy males successfully completed the trial, after randomly receiving in a double-blind manner an oral dose of low dose (150 mg) or high dose (225 mg) ATP, or matched placebo. To improve absorption characteristics, the ATP was enterically coated. Total blood ATP (whole blood and plasma ATP) concentrations, two Wingate anaerobic power tests (30 s), and muscular strength (1RM and three sets of repetitions to fatigue at 70% of 1RM) were measured under three conditions: (i) baseline; (ii) acutely (7d later, no prior supplementation and 75 min after ATP ingestion); and (iii) after 14 d of daily ingestion (post). Results: Statistical analyses showed no significant between or within group treatment effects for whole blood ATP or plasma ATP concentrations for any treatment condition. We also did not observe any treatment effects for any Wingate testing parameter including peak PO, total work, average PO for 30 s, or post-Wingate lactate accumulation. Overall, we observed no significant between group treatment effects for any muscular strength parameter. We did observe several within group differences for the group ingesting the high ATP dosage including 1RM (6.6%; P < 0.04) and repetitions to fatigue during set 1 of posttesting (18.5%; P < 0.007) and total lifting volume at post (22%; P < 0.003). Conclusions: We conclude that enterically coated oral ATP supplementation may provide small ergogenic effects on muscular strength under some treatment conditions.Sin financiación2.525 JCR (2004) Q1, 3/71 Sport sciencesUE

Reflection of Metanarratives in Youth Online Communities (on the Example of VK and Telegram)

«Цифровая молодежь», или поколение Z, составляет почти треть населения России. Медиапотребление молодых россиян сосредоточено преимущественно в цифровой среде, а именно – в социальных медиа. В данном исследовании представлены медианарративы, выявленные в популярных у молодежи сообществах на платформах VK и Telegram, отражающие метанарративы российского общества. Было определено, что в повестке дня «цифровой молодежи» превалируют медианарративы, направленные на воспитание патриотизма, исторической памяти, традиционных семейных ценностей и здорового образа жизни. Между тем присутствуют и «небезопасные медианарративы», обращающие внимание на наличие в стране проблем, коррупции в регионах, одобряющие употребление алкоголя и курение“Digital youth”, or generation Z, makes up almost one third of the Russian population. Media consumption of young Russians is mainly concentrated in the digital space, more precisely, in social media. This study presents media narratives identified in communities popular among young people on the VK and Telegram platforms, reflecting the metanarratives of Russian society. Thus, the agenda of “digital youth” is dominated by media narratives aimed at fostering patriotism, historical memory, traditional family values and a healthy lifestyle. Meanwhile, there are also “unsafe medianarratives” that draw attention to the presence of problems in the country, corruption in the regions, approving the use of alcohol and smokin

Extracellular vesicles of human glial cells exert neuroprotective effects via brain miRNA modulation in a rat model of traumatic brain injury

Abstract Stem cell-based therapeutic approaches for neurological disorders are widely studied. Paracrine factors secreted by stem cells in vitro and delivered intranasally might allow bypassing the disadvantages associated with a surgical cell delivery procedure with likely immune rejection of a transplant. In this study, we investigated the therapeutic effect of the extracellular vesicles secreted by glial progenitor cells (GPC-EV) derived from human induced pluripotent stem cell in a traumatic brain injury model. Intranasal administration of GPC-EV to Wistar rats for 6 days improved sensorimotor functions assessed over a 14-day observation period. Beside, deep sequencing of microRNA transcriptome of GPC-EV was estimate, and was revealed 203 microRNA species that might be implicated in prevention of various brain pathologies. Modulation of microRNA pools might contribute to the observed decrease in the number of astrocytes that inhibit neurorecovery processes while enhancing neuroplasticity by decreasing phosphorylated Tau forms, preventing inflammation and apoptosis associated with secondary damage to brain tissue. The course of GPC-EV administration was promoted the increasing protein levels of NF-κB in studied areas of the rat brain, indicating NF-κB dependent mechanisms as a plausible route of neuroprotection within the damaged area. This investigation showed that GPC-EV may be representing a therapeutic approach in traumatic brain injury, though its translation into the clinic would require an additional research and development

Dynamic trafficking and turnover of JAM-C is essential for endothelial cell migration

Junctional complexes between endothelial cells form a dynamic barrier that hinders passive diffusion of blood constituents into interstitial tissues. Remodelling of junctions is an essential process during leukocyte trafficking, vascular permeability, and angiogenesis. However, for many junctional proteins, the mechanisms of junctional remodelling have yet to be determined. Here, we used receptor mutagenesis, horseradish peroxidase (HRP), and ascorbate peroxidase 2 (APEX-2) proximity labelling, alongside light and electron microscopy (EM), to map the intracellular trafficking routes of junctional adhesion molecule-C (JAM-C). We found that JAM-C cotraffics with receptors associated with changes in permeability such as vascular endothelial cadherin (VE-Cadherin) and neuropilin (NRP)-1 and 2, but not with junctional proteins associated with the transmigration of leukocytes. Dynamic JAM-C trafficking and degradation are necessary for junctional remodelling during cell migration and angiogenesis. By identifying new potential trafficking machinery, we show that a key point of regulation is the ubiquitylation of JAM-C by the E3 ligase Casitas B-lineage lymphoma (CBL), which controls the rate of trafficking versus lysosomal degradation.TDN, CS, and KBK were funded by an MRC project grant MR/M019179/1. KBK also received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n° 608765. AB and TPM were funded by QMUL. SN was funded by a Wellcome Trust investigator award 098291/Z/12/Z. MA was funded by Canceropôle PACA (Valo-Paca 2016) and French National Institute of Cancer (Inca, PRT-K16, #2017-24). PC and VR were funded by BBSRC (BB/M006174/1) and the Barts and The London Charity (297/2249). IJW was funded by an MRC LMCB core grant award MC_U12266B