Villumsenmouritzen8663
CD8
CD25
fork-head box transcription factor (Foxp3)
regulatory T cells (CD8
Tregs) play a role in immune tolerance. However, the role of these cells in allergic rhinitis (AR) has not been elucidated. The study aimed to evaluate influences of CD8
Tregs on inflammatory conditions in a murine model of AR.
A murine model of AR was established. CD8
Tregs were isolated from mice nasal mucosa and cultured in vitro. We examined interleukin (IL)-10 and transforming growth factor (TGF)-β in cell cultures. Then, we administered CD8
Tregs into mice nasal mucosal cultures, and examined eosinophil cation protein (ECP), IL-4, IL-5 and IL-13 in these cultures. Finally, we adoptively transferred CD8
Tregs into mice models, and evaluated percentages of CD8
Tregs, numbers of sneezing and nasal rubbing, and counts of eosinophils and contents of ECP, IL-4, IL-5, IL-13, IL-10 and TGF-β in nasal lavage fluid (NLF) in mice.
The percentage of CD8
Tregs from AR mice was reduced. IL-10 and TGF-β were increased in cell cultures from AR mice. ECP, IL-4, IL-5 and IL-13 were decreased after the AR mice CD8
Tregs administration in mucosal cultures. However, their contents were not changed after normal CD8
Tregs treatment. Additionally, the adoptive transfer of AR CD8
Tregs enhanced the percentage of CD8
Tregs and levels of IL-10 and TGF-β in NLF, reduced numbers of sneezing and nasal rubbing, and counts of eosinophils and concentrations of ECP, IL-4, IL-5 and IL-13 in NLF. However, normal CD8
Tregs could not change above parameters.
These findings show that CD8
Tregs may inhibit inflammatory responses in the AR condition.
These findings show that CD8+ Tregs may inhibit inflammatory responses in the AR condition.
Sub-Saharan Africa continues to carry a high burden of communicable diseases such as TB and HIV and non-communicable diseases such as hypertension and other cardiovascular conditions. Although investment in research has led to advances in improvements in outcomes, a lot still remains to be done to build research capacity in health. Like many other regions in the world, Sub-Saharan Africa suffers from a critical shortage of biostatisticians and clinical trial methodologists.
Funded through a Fogarty Global Health Training Program grant, the Faculty of Medicine and Health Sciences at Stellenbosch University in South Africa established a new Masters Program in Biostatistics which was launched in January 2017. In this paper, we describe the development of a biostatistical and clinical trials collaboration Module, adapted from a similar course offered in the Health Research Methodology program at McMaster University.
Guided by three core principles (experiential learning; multi-/inter-disciplinary approach; and formal mentorship), the Module aims to advance biostatistical collaboration skills of the trainees by facilitating learning in how to systematically apply fundamental statistical and trial methodological knowledge in practice while strengthening some soft skills which are necessary for effective collaborations with other healthcare researchers to solve health problems. We also share some preliminary findings from the first four cohorts that took the Module in January-November 2018 to 2021. We expect that this Module can provide an example of how to improve biostatistical and clinical trial collaborations and accelerate research capacity building in low-resource settings.
Fogarty International Center of the National Institutes of Health.
Fogarty International Center of the National Institutes of Health.Metabolic rewiring offers novel therapeutic opportunities in cancer. GSK-3 phosphorylation Until recently, there was scant information regarding soft tissue sarcomas, due to their heterogeneous tissue origin, histological definition and underlying genetic history. Novel large-scale genomic and metabolomics approaches are now helping stratify their physiopathology. In this review, we show how various genetic alterations skew activation pathways and orient metabolic rewiring in sarcomas. We provide an update on the contribution of newly described mechanisms of metabolic regulation. We underscore mechanisms that are relevant to sarcomagenesis or shared with other cancers. We then discuss how diverse metabolic landscapes condition the tumor microenvironment, anti-sarcoma immune responses and prognosis. Finally, we review current attempts to control sarcoma growth using metabolite-targeting drugs.
Intracerebral hemorrhage (ICH) is a major public health concern, and mesenchymal stem cells (MSCs) hold great potential for treating ICH. However, the quantity and quality of MSCs decline in the cerebral niche, limiting the potential efficacy of MSCs. Hypoxic preconditioning is suggested to enhance the survival of MSCs and augment the therapeutic efficacy of MSCs in ICH. MicroRNAs (miRNAs) are known to mediate cellular senescence. However, the precise mechanism by which miRNAs regulate the senescence of hypoxic MSCs remains to be further studied. In the present study, we evaluated whether hypoxic preconditioning enhances the survival and therapeutic effects of olfactory mucosa MSC (OM-MSC) survival and therapeutic effects in ICH and investigated the mechanisms by which miRNA ameliorates hypoxic OM-MSC senescence.
In the in vivo model, ICH was induced in mice by administration of collagenase IV. At 24 h post-ICH, 5 × 10
normoxia or hypoxia OM-MSCs or saline was administered intracerebrally. The behavioraermore, we showed that miR-326 alleviated cellular senescence by upregulating autophagy. Mechanistically, miR-326 promoted the autophagy of OM-MSCs via the PI3K signaling pathway by targeting polypyrimidine tract-binding protein 1 (PTBP1).
Our study shows that hypoxic preconditioning delays OM-MSC senescence and augments the therapeutic efficacy of OM-MSCs in ICH by upregulating the miR-326/PTBP1/PI3K-mediated autophagy.
Our study shows that hypoxic preconditioning delays OM-MSC senescence and augments the therapeutic efficacy of OM-MSCs in ICH by upregulating the miR-326/PTBP1/PI3K-mediated autophagy.
Despite the high prevalence of common mental disorders in adolescents and young adults, and their association with poor health and socio-economic outcomes throughout the lifespan, many young people do not seek or receive help for such disorders. There is growing interest in the community sector in supporting mental health in young people; however, there is little by way of experimental research in this area. During the COVID-19 pandemic and lockdown, we designed an online cultural experience to reduce anxiety and depression and support mental health in people aged 16-24.
The O-ACE POP (Online Active Community Engagement Proof of Principle) study is a UK-based online randomised controlled trial of an online cultural experience named Ways of Being, involving human centred narratives and viewpoints, compared with a typical museum website (the Ashmolean Museum). We aim to compare efficacy on affect, symptoms ofepression and anxiety, flourishing and loneliness as well as investigating potential mechanisms of action.
The COVID-19 pandemic has provided a unique opportunity to design an innovative approach to supporting mental health in young adults. Findings derived from this study will allow us to evaluate the efficacy of this intervention and will inform the design of studies to further refine the resource and test it further.
ClinicalTrials.gov NCT04663594. Registered on 11 December 2020 (submitted in same form 27 November 2020). Protocol v1.0 27 November 2020. Date recruitment began 4 December 2020. Recruitment complete (estimate) February 2021.
ClinicalTrials.gov NCT04663594. Registered on 11 December 2020 (submitted in same form 27 November 2020). Protocol v1.0 27 November 2020. Date recruitment began 4 December 2020. Recruitment complete (estimate) February 2021.
During aging, hematopoietic stem cells (HSC) lose progressively both their self-renewal and differentiation potential. The precise molecular mechanisms of this phenomenon are not well established. To uncover the molecular events underlying this event, we have performed a bioinformatics analysis of 650 single-cell transcriptomes.
Single-cell transcriptome analyses of expression heterogeneity, cell cycle, and cell trajectory in human cell compartment enriched in hematopoietic stem cell compartment were investigated in the bone marrow according to the age of the donors. Identification of aging-related nodules was identified by weighted correlation network analysis in this primitive compartment.
The analysis of single-cell transcriptomes allowed to uncover a major upregulation of EGR1 in human-aged lineage-CD34+CD38- cells which present cell cycle dysregulation with reduction of G2/M phase according to less expression of CCND2 during S phase. EGR1 upregulation in aging hematopoietic stem cells was found to lated transcriptional program in aged human HSCs. EGR1 and its program were found to be connected to the aging of human HSC with dissociation of quiescence property and cell cycle phase progression in this primitive hematopoietic compartment.
EGR1 was found to be connected to the aging of human HSC and highlighted a specific cell trajectory contributing to the dysregulation of an inflammatory and leukemia-related transcriptional program in aged human HSCs. EGR1 and its program were found to be connected to the aging of human HSC with dissociation of quiescence property and cell cycle phase progression in this primitive hematopoietic compartment.
Reproductive genetic carrier screening is a type of genetic testing available to those planning a pregnancy, or during their first trimester, to understand their risk of having a child with a severe genetic condition. There is a lack of consensus for 'what to measure' in studies on this intervention, leading to heterogeneity in choice of outcomes and methods of measurement. Such outcome heterogeneity has implications for the quality and comparability of these studies and has led to a lack of robust research evidence in the literature to inform policy and decision-making around the offer of this screening. As reproductive genetic carrier screening becomes increasingly accessible within the general population, it is timely to investigate the outcomes of this intervention.
The development of a core outcome set is an established methodology to address issues with outcome heterogeneity in research. We aim to develop a core outcome set for reproductive genetic carrier screening to clarify and standardise outcomdevelopment process and its novel application in the setting of genetic testing. This core outcome set will support the standardisation of outcome reporting in reproductive carrier screening research and contribute to an evolving literature on outcomes to evaluate genetic testing and genetic counselling as health interventions. COMET CORE OUTCOME SET REGISTRATION http//www.comet-initiative.org/Studies/Details/1381 .
This protocol outlines the core outcome set development process and its novel application in the setting of genetic testing. This core outcome set will support the standardisation of outcome reporting in reproductive carrier screening research and contribute to an evolving literature on outcomes to evaluate genetic testing and genetic counselling as health interventions. COMET CORE OUTCOME SET REGISTRATION http//www.comet-initiative.org/Studies/Details/1381 .
