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Thus, although potentially beneficial in short term, inducing mitochondrial biogenesis with bezafibrate altered the metabolomic signature of mitochondrial disease, raising concerns about long-term sequelae. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.Macrophages are characterized by a high plasticity in response to changes in tissue microenvironment, which allows them to acquire different phenotypes and to exert essential functions in complex processes, such as tissue regeneration. Here, we report that the membrane protein Cripto plays a key role in shaping macrophage plasticity in skeletal muscle during regeneration and disease. Conditional deletion of Cripto in the myeloid lineage (CriptoMy-LOF ) perturbs MP plasticity in acutely injured muscle and in mouse models of Duchenne muscular dystrophy (mdx). Specifically, CriptoMy-LOF macrophages infiltrate the muscle, but fail to properly expand as anti-inflammatory CD206+ macrophages, which is due, at least in part, to aberrant activation of TGFβ/Smad signaling. This reduction in macrophage plasticity disturbs vascular remodeling by increasing Endothelial-to-Mesenchymal Transition (EndMT), reduces muscle regenerative potential, and leads to an exacerbation of the dystrophic phenotype. Thus, in muscle-infiltrating macrophages, Cripto is required to promote the expansion of the CD206+ anti-inflammatory macrophage type and to restrict the EndMT process, providing a direct functional link between this macrophage population and endothelial cells. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.AIMS Cognitive impairment is common in systemic lupus erythematosus (SLE) patients with substantial adverse effects on function and quality of life. One hypothesis to understand the mechanisms of cognitive impairment in SLE is accelerated immunosenescence. The aim of this study is to observe the correlation between immunosenescence with cognitive impairment in patients with SLE. METHODS Sixty-one female SLE patient were measured for CD4 and CD8 T cell-associated senescence markers, including percentage of end-stage differentiated T cells (CD4 and CD8 T cells expressing CD57+ or loss of CD28 expression), of naïve T cells (CD4+ CD45RA+ and CD8+ CD45RA+ ), memory T cells (CD4+ CD45RO+ and CD8+ CD45RO+ ), and antigen-experienced T cells (CD4+ KLRG1+ and CD8+ KLRG1+ ) which were measured using flow cytometry. One hallmark of immunosenescence called immune risk profile (IRP) was defined by an inverted ratio of CD4 and CD8. Cognitive functions were measured by Mini-Mental State Examination (MMSE) and Montréal Cognitive Assessment (MOCA) questionnaire. RESULTS Thirty-six (59.1%) SLE patients who had IRP develop significantly lower attention and recall from both MMSE (P = .005 and P = .000) and MOCA (P = .017 and P = .000) examinations. Decreased visuospatial ability was also found in patients with IRP measured by MOCA (P = .046). There was a negative correlation between memory CD4+ CD45RO+ T cells with recall and visuospatial domain (R = -0.204, P = .039 and R = -0.250, P = .033; respectively), and negative correlation between CD8+ CD28- T cells with recall and attention domain (R = -0.249, P = .027 and R = -0.145, P = .048, respectively). CONCLUSION Systemic lupus erythematosus patients develop an accelerated immunosenescence which contributes to cognitive dysfunction, especially in attention, recall, and visuospatial domains. © 2020 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.BACKGROUND Circular RNA (circRNA) is a novel molecular marker and target candidate that is closely associated with tumor invasion and migration. The mechanism of action of hsa_circ_0005035 (circ-IGF1R) in non-small cell lung cancer remains unclear. In this study, we aimed to study the mechanism of action of circ-IGF1R in lung cancer. METHODS We screened circ-IGF1R, one of the most notable differential expressions, from the Gene Expression Omnibus database, GSE104854, for further research. The expression level of circ-IGF1R was examined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in five different lung cancer cell lines and 50 pairs of lung cancer and adjacent tissues. Wound-healing and Transwell assays were used for verifying the biological function of circ-IGF1R. The effect of overexpressing circ-IGF1R on the transcriptome of whole lung cancer cells was explored in lung cancer cell lines using RNA-seq. RESULTS The expression level of circ-IGF1R was notably lower in lung cancer tissues and lung cancer cell lines than in the adjacent normal tissues and cells (P  less then  0.0001). In addition, the expression level of circ-IGF1R was associated with larger tumors (T2/T3/T4) and lymph node metastasis (N1/ N2/N3) (P  less then  0.05). The overexpression of circ-IGF1R significantly inhibited the invasion and migration of the lung cancer cells. The potential network of circ-IGF1R-miR-1270-VANGL2 was preliminarily determined, and the expression patterns of miR-1270 and VANGL2 were verified in lung cancer cell lines. CONCLUSION Circ-IGF1R may inhibit lung cancer invasion and migration through a potential network of circ-IGF1R-miR-1270-VANGL2. © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.Ranitidine has been the topic of recent media reports. Current findings, confirmed by the US Food and Drug Administration, indicate that some ranitidine products contain a substance that may be carcinogenic. Providers and patients require additional information on the risks of continuing therapy vs. the benefits of the medication. This article comments on what is currently known about the evolving situation of elevated N-nitrosodimethylamine levels in ranitidine and the limits of the existing information to assess best practices. © 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. Tariquidar research buy on behalf of the American Society for Clinical Pharmacology and Therapeutics.BACKGROUND In the recent case of R v Taj, the Court of Appeal of England & Wales upheld the conviction of a defendant who, in a psychotic delusional state, mistook his non-threatening victim to be a terrorist, violently attacking him. The law typically allows honest mistakes (even if unreasonable) as a basis for self-defence (in this case the defence of others). But because Taj’s delusions were found by the court to have been caused by voluntary alcohol consumption, special legal (prior-fault) intoxication rules were applied to block his defence; Taj was convicted and sentenced to 19 years for attempted murder. ARGUMENT We focus here on the simple question – what does it mean to be intoxicated? On the facts, Taj did not have drugs active in his system at the time of the attack, but the court nonetheless insisted that Taj’s delusional mistake was ‘attributable to intoxication’, namely to drink and drug-taking in the previous days and weeks. This extended conception of intoxication was questionably distinguished from psychosis induced by withdrawal.