Crowderholdt1905
To explore the correlation of mutation landscape with clinical outcomes in patients with peripheral T-cell lymphoma (PTCL).
We retrospectively analyzed the clinicopathological and prognosis data of 53 patients with PTCL from November 2011 to December 2017. Targeted next-generation sequencing of a 659-gene panel was performed for tissues from 53 patients with PTCLs. The correlation of mutation landscape with clinical outcomes was analyzed.
TET2 was the most frequently mutated gene (64%), followed by RHOA (43%), PCLO (23%), DNMT3A (19%), IDH2 (17%), PIEZO1 (17%) and TP53 (15%). When mutated genes were categorized into functional groups, the most common mutations were those involved in epigenetic/chromatin modification (75%), T-cell activation (74%), and the DNA repair/TP53 pathway (64%). TET2/TP53 mutations were significantly associated with positive B symptoms (P = 0.045), and elevated lactate dehydrogenase (LDH) level (P = 0.011). Moreover, TET2/TP53 mutation was a risk factor for PTCL patient survival (HR 3.574, 95% CI 1.069- 11.941, P = 0.039). check details The occurrence of JAK/STAT pathway mutations in angioimmunoblastic T-cell lymphoma (AITL) patients conferred a worse progression-free survival (HR 2.366, 95% CI 0.9130-6.129, P = 0.0334).
Heterogeneous gene mutations occur in PTCL, some of which have a negative impact on the survival outcome.
Heterogeneous gene mutations occur in PTCL, some of which have a negative impact on the survival outcome.
Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake-via AMP-activated protein kinase (AMPK)-after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR).
Cultured cardiomyocytes were stimulated with 100nM testosterone for 24h, and hypertrophy was verified by increased cell size and mRNA levels of β-myosin heavy chain (β-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR).
Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5weeks induced cardiac hypertrophy and upregulated β-mhc, Hk2 and Pfk2 mRNA levels.
These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.
These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.
Psychosocial health issues such as depression and social isolation are an important cause of morbidity and premature mortality for older adults and people with dementia. Social robots are promising technological innovations to deliver effective psychosocial interventions to promote psychosocial wellbeing. Studies have reported positive findings regarding this technology on the psychosocial health of older adults and people with dementia. However, despite positive findings of the effects of social robots for older adults and people with dementia, little is known about factors affecting their implementation in practice.
This study follows Arksey and O'Malley's approach and methodological enhancement by Levac et al. Relevant articles will be identified by searching electronic databases MEDLINE, Embase, PsycINFO, Scopus, Web of Science, Compendex and PubMed. A two-phase screening process will be undertaken by two independent reviewers to determine articles' inclusion. Findings will be summarised and reported l from a research ethics board.
Our protocol is registered with the Open Science Framework ( https//osf.io/2x3y9/ ) as an open access article, under the Creative Commons Attribution Non Commercial (CC BY-NC-4.0) license, which allows others to distribute, remix, adapt and build on this work on a non-commercial basis, and license their derivative work using different terms, on the basis that the original basis is properly cited and the use is non-commercial ( http//creativecommons.org/licenses/by-nc/4.0/ ).
Our protocol is registered with the Open Science Framework ( https//osf.io/2x3y9/ ) as an open access article, under the Creative Commons Attribution Non Commercial (CC BY-NC-4.0) license, which allows others to distribute, remix, adapt and build on this work on a non-commercial basis, and license their derivative work using different terms, on the basis that the original basis is properly cited and the use is non-commercial ( http//creativecommons.org/licenses/by-nc/4.0/ ).
Historically the main source of laboratory Xenopus laevis was the environment. The increase in genetically altered animals and evolving governmental constraints around using wild-caught animals for research has led to the establishment of resource centres that supply animals and reagents worldwide, such as the European Xenopus Resource Centre. In the last decade, centres were encouraged to keep animals in a "low microbial load" or "clean" state, where embryos are surface sterilized before entering the housing system; instead of the conventional, "standard" conditions where frogs and embryos are kept without prior surface treatment. Despite Xenopus laevis having been kept in captivity for almost a century, surprisingly little is known about the frogs as a holobiont and how changing the microbiome may affect resistance to disease. This study examines how the different treatment conditions, "clean" and "standard" husbandry in recirculating housing, affects the skin microbiome of tadpoles and female adults. Thiadult Xenopus laevis microbiome is controlled and selected by the host. This indicates that the surface microbiome of adult Xenopus laevis is stable and defined independently of the environment in which it is housed, suggesting that the use of clean husbandry conditions poses little risk to the skin microbiome when transferring adult frogs to research laboratories. This will have important implications for frog health applicable to Xenopus laevis research centres throughout the world.
Hypothermic machine perfusion (HMP) improves the quality of donor livers for transplantation, both in animal models and in clinical practice. Treatment with SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), can suppress the JNK signaling pathway to alleviate donor liver ischemia-reperfusion injury (IRI). We performed the present study with the objective of exploring the protective effects exerted by a combination of HMP and SP600125 on liver xenograft viability for donation after cardiac death (DCD) in a porcine model.
54 adult BAMA mini-pigs were randomly assigned to 5 groups, including sham, cold storage for 4h (CS 4h), CS 4h + SP600125, CS 2h + HMP 2h, and CS 2h + HMP 2h + SP600125 groups. Donor livers in the CS 4h and CS 4h + SP600125 groups were conventionally cold preserved for 4h, whereas donor livers in the CS 2h + HMP 2h and CS 2h + HMP 2h + SP600125 groups were cold preserved for 2h and then treated with HMP for 2h. The preservation and perfusion solutions contained SP600125 (20µM). Follow-up was conducted for 5days after liver transplantation to compare the surgical outcomes by means of serological examination, pathological results, and survival rate.
The most satisfactory outcome after liver transplantation was observed in the CS 2h + HMP 2h + SP600125 group, which presented with minimal damage of donor livers during 5days' follow-up. Additionally, serological examination, pathological results, and survival rate concurred in showing better results in the CS 2h + HMP 2h ± SP600125 group than in the CS 4h ± SP600125 group.
HMP in combination with SP600125 has hepatoprotective properties and improves the quality and viability of porcine livers collected after DCD, thus improving prognosis after liver transplantation.
HMP in combination with SP600125 has hepatoprotective properties and improves the quality and viability of porcine livers collected after DCD, thus improving prognosis after liver transplantation.Swelling and the progressive destruction of articular cartilage are major characteristics of rheumatoid arthritis (RA), a systemic autoimmune disease that directly affects the synovial joints and often causes severe disability in the affected positions. Recent studies have shown that type B synoviocytes, which are also called fibroblast-like synoviocytes (FLSs), as the most commonly and chiefly resident cells, play a crucial role in early-onset and disease progression by producing various mediators. During the pathogenesis of RA, the FLSs' phenotype is altered, and represent invasive behavior similar to that observed in tumor conditions. Modified and stressful microenvironment by FLSs leads to the recruitment of other immune cells and, eventually, pannus formation. The origins of this cancerous phenotype stem fundamentally from the significant metabolic changes in glucose, lipids, and oxygen metabolism pathways. Moreover, the genetic abnormalities and epigenetic alterations have recently been implicated in cancer-like behaviors of RA FLSs. In this review, we will focus on the mechanisms underlying the transformation of FLSs to a cancer-like phenotype during RA. A comprehensive understanding of these mechanisms may lead to devising more effective and targeted treatment strategies.
Depression is one of the most prevalent mental disorders among an estimated 25.6 million people living with HIV (PLHIV) in sub-Saharan Africa (SSA). The depression rate is higher in HIV-seropositive men who have sex with men (MSM) regardless of their sexual orientation, identity or romantic attraction. This is due to various types of stigma including HIV-related stigma, social stigma, self-stigma and mental health stigma. Opportunistic infections, unemployment, poverty and food insecurity also predispose HIV-seropositive MSM to depression. link2 Moreover, depression in heterosexual and sexual minority groups challenges and additionally burdens SSA health care systems due to inadequate economic developments, lack of mental health professionals who specialise in the treatment of depression, few MSM-centred facilities, inadequate mental health infrastructure (hospitals and clinics) and complimentary resources. Although studies have highlighted links between mental health disorder, an HIV diagnosis and sexual minoritg in SSA.
Nicotinamide phosphoribosyltransferase (NAMPT) regulates cellular functions through the protein deacetylation activity of nicotinamide adenine dinucleotide (NAD
)-dependent sirtuins (SIRTs). SIRTs regulate functions of histones and none-histone proteins. link3 The role of NAMPT/SIRT pathway in the regulation of maintenance and differentiation of human-induced pluripotent stem (iPS) cells is not fully elucidated.
We evaluated the effects of specific inhibitors of NAMPT or SIRT2 on the pluripotency, proliferation, survival, and hematopoietic differentiation of human iPS cells. We also studied the molecular mechanism downstream of NAMPT/SIRTs in iPS cells.
We demonstrated that NAMPT is indispensable for the maintenance, survival, and hematopoietic differentiation of iPS cells. We found that inhibition of NAMPT or SIRT2 in iPS cells induces p53 protein by promoting its lysine acetylation. This leads to activation of the p53 target, p21, with subsequent cell cycle arrest and induction of apoptosis in iPS cells. NAMPT and SIRT2 inhibition also affect hematopoietic differentiation of iPS cells in an embryoid body (EB)-based cell culture system.
