Notes

Your Interplay associated with Glucagon-Like Peptide-1 Receptor Trafficking and also Signalling within Pancreatic Beta Tissue.
INTRODUCTION Left bundle branch pacing (LBBP) is a promising new method for patients with pacing indications. This study aims to evaluate the safety and feasibility of LBBP in a relatively longer time span. METHODS AND RESULTS A total of 164 patients were recruited for LBBP in this study. Among these patients, 148 patients had pacing indications due to symptomatic bradycardia while the other 16 patients had indications for cardiac resynchronization therapy (CRT). LBBP was successful in 89.0% (146/164) of all recruited patients. Intracardiac and surface electrographic parameters and image data were documented during the LBBP procedure. The mean paced QRS duration (pQRSD) and the mean stimulus to left ventricular activation time (stim-LVAT) was 106.0 ± 12.9 ms and 64.4 ± 13.7 ms respectively. Left bundle branch (LBB) potentials were recorded in 89 patients. Forty-three of whom had sick sinus syndrome (SSS), and 46 had atrioventricular block (AVB). The presence of LBB potential was more common in patients with SSS (82.7% vs 57.5%, P = .002). No significant differences in pQRSD, stim-LVAT, or capture threshold were detected between patient groups with or without LBB potential. Patients were followed up at 1 month, 3 months, 6 months, and 1 year after the procedure. Pacing parameters and the echocardiographic data remained stable within a mean follow-up period of 8.6 ± 4.3 months. No serious complication caused by this procedure was found in this study. CONCLUSIONS Successful LBBP carried an aspect of short pQRSD and stim-LVAT while the LBB potential was not the prerequisite and necessary feature. The LBBP procedure had a high success rate with satisfied and stable lead parameters during short and intermediate-term observations. © 2020 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.Telomerase (hTERT) reactivation and sustained expression is a key event in the process of cellular transformation. Therefore, the identification of the mechanisms regulating hTERT expression is of great interest for the development of new anticancer therapies. Although the epigenetic state of hTERT gene promoter is important, we still lack a clear understanding of the mechanisms by which epigenetic changes affect hTERT expression. Retinoids are well-known inducers of granulocytic maturation in acute promyelocytic leukemia (APL). We have previously shown that retinoids repressed hTERT expression in the absence of maturation leading to growth arrest and cell death. Exploring the mechanisms of this repression, we showed that transcription factor binding was dependent on the epigenetic status of hTERT promoter. In the present study, we used APL cells lines and publicly available datasets from APL patients to further investigate the integrated epigenetic events that promote hTERT promoter transition from its silent to its active state, and inversely. We showed, in APL patients, that the methylation of the distal domain of hTERT core promoter was altered and correlated with the outcome of the disease. Further studies combining complementary approaches carried out on APL cell lines highlighted the significance of a domain outside the minimal promoter, localized around 5 kb upstream from the transcription start site, in activating hTERT. This domain is characterized by DNA hypomethylation and H3K4Me3 deposition. Our findings suggest a cooperative interplay between hTERT promoter methylation, chromatin accessibility, histone modifications that force the revisiting of previously proposed concepts regarding hTERT epigenetic regulation. They represent, therefore, a major advance in predicting sensitivity to retinoid-induced hTERT repression and, more generally, in the potential development of therapies targeting hTERT expression in cancers. This article is protected by copyright. All rights reserved.Nivolumab, a fully human IgG4 immune checkpoint modulator, binds to the programmed cell death 1 (PD-1) receptor on T cells and blocks their inhibition. Thus, it increases the anticancer host immune response by allowing T cells to attack tumor cells. Although anti-PD-1 immunotherapy is typically well accepted, deregulation of immune tolerance caused by nivolumab may determine immune-related adverse events, among which skin toxicities represent the most common. We report a case of severe new-onset palmoplantar and nail psoriasis after receiving nivolumab treatment for metastatic melanoma. © 2020 Wiley Periodicals LLC.As a potential antitumor herbal medicine, plantamajoside (PMS) benefits the treatment of many human malignances. However, the role of PMS in the progression of hepatocellular carcinoma (HCC) and the related molecular mechanisms is still unknown. Here, we proved that the cell viabilities of HepG2 cells were gradually decreased with the increasing concentrations of CoCl2 and/or PMS via cell counting kit-8 assay. Meanwhile, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and western blot assays were used to further confirm that PMS inhibited the CoCl2 -induced cell proliferation in HepG2 cells via suppressing the Ki67 and proliferating cell nuclear antigen expressions. We also performed wound-healing and transwell assays and demonstrated that PMS inhibited CoCl2 -induced migration and invasion in HepG2 cells via suppressing the epithelial-mesenchymal transition (EMT) process. In addition, the use of 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole further proved that PMS inhibited the malignant biological behaviors of HepG2 cells under hypoxic condition by suppressing the hypoxia-inducible factor-1α (HIF-1α) expression. Besides, we further confirmed that PMS suppressed the growth and metastasis of implanted tumors in vivo. Given that PMS suppressed the proliferation and EMT induced by CoCl2 in HCC cells via downregulating HIF-1α signaling pathway, we provided evidence that PMS might be a novel anti-cancer drug for HCC treatment. © 2020 International Federation for Cell Biology.In late life, traumas may act cumulatively to exacerbate vulnerability to post-traumatic stress disorder (PTSD). PTSD is also a risk factor for cognitive decline. Major neurocognitive disorder (MND) can be associated with worsening of already controlled PTSD symptoms, late-life resurgence or de novo emergence. Misidentifying PTSD symptoms in MND can have negative consequences for the patient and families. We review the literature pertaining to PTSD and dementia and describe five cases referred for consultation in geriatric psychiatry initially for behavioural and psychological symptoms of dementia (BPSD), which were eventually diagnosed and treated as PTSD in MND subjects. We propose that certain PTSD symptoms in patients with MND are misinterpreted as BPSD and therefore, not properly addressed. For example, flashbacks could be interpreted as hallucinations, hypervigilance as paranoia, nightmares as sleep disturbances, and hyperreactivity as agitation/aggression. We suggest that better identification of PTSD symptoms in MND is needed. We propose specific recommendations for care, namely clarifying diagnosis by distinguishing PTSD symptoms coexisting with different types of dementia from a specific dementia symptom (BPSD), gathering a detailed history of the trauma in order to personalise non-pharmacological interventions, adapting psychotherapeutic strategies to patients with dementia, using selective serotonin reuptake inhibitors as first-line treatment and avoiding antipsychotics and benzodiazepines. Proper identification of PTSD symptoms in patients with MND is essential and allows a more tailored and efficient treatment, with decrease in inappropriate use of physical and chemical restraints. © 2020 Japanese Psychogeriatric Society.Intensive crop production systems worldwide, particularly in China, rely heavily on nitrogen (N) fertilization, but left more than 50% of it in the environment. Nitrogen (over)fertilization and atmospheric N deposition induce soil acidification, which is neutralized by soil inorganic carbon (SIC; carbonates) and carbon dioxide (CO2 ) is released to the atmosphere. For the first time, the loss of SIC stocks in response to N-induced soil acidification was estimated from Chinese croplands from 1980 to 2020 and forecasts were made up to 2100. The SIC stocks in croplands in 1980 were 2.16 Pg C (16.3 Mg C ha-1 ) in the upper 40 cm, 7% (0.15 Pg C; 1.1 Mg C ha-1 ) of which were lost from 1980 to 2020. During these 40 years, 7 million ha of cropland has become carbonate free. Another 37% of the SIC stocks may be lost up to 2100 in China, leaving 30 million ha of cropland (37.8%) without carbonates if N fertilization follows the business as usual (BAU) scenario. Compared to the BAU scenario, the reduction of N input by 15%-30% after 2020 (scenarios S1 and S2) will decrease carbonates dissolution by 18%-41%. If N input remains constant as noted in 2020 (S3) or decreases by 1% annually (S4), a reduction of up to 52%-67% in carbonates dissolution is expected compared to the BAU. The presence of CaCO3 in the soil is important for various processes including acidity buffering, aggregates formation and stabilization, organic matter stabilization, microbial and enzyme activities, nutrients cycling and availability, and water permeability and plants productivity. Therefore, optimizing N fertilization and improving N use efficiency are important for decreasing SIC losses from acidification. N application should be strictly calculated based on crop demand, and any overfertilization should be avoided to prevent environmental problems and soil fertility decline associated with CaCO3 losses. This article is protected by copyright. All rights reserved.BACKGROUND & AIMS Coronavirus disease 2019 (COVID-19) has raised world concern for global epidemic since December, 2019. Limited data are available for liver function in COVID-19 patients. We aimed to investigate the risk factors related to liver injury in the COVID-19 patients. METHODS A retrospective study was performed in non-ICU Ward at Jinyintan Hospital from February 2, 2020 to February 23, 2020. Consecutively confirmed COVID-19 discharged cases were enrolled. The clinical characteristics of patients with liver injury and without liver injury were compared. RESULTS A total of 79 COVID-19 patients were included. 31.6%, 35.4% and 5.1% COVID-19 patients had elevated levels of alanine transaminase (ALT), aspartate aminotransferase (AST) and bilirubin respectively. Median value of ALT, AST and bilirubin for entire cohort was 36.5 (17.5 ~ 71.5) U/L, 34.5 (25.3 ~ 55.3) U/L and 12.7 (8.1 ~ 15.4) mmol/L respectively. There were no significant differences in age, previous medical history and symptoms between the two groups. Nimodipine solubility dmso Males were more likely to have liver injury when infected with COVID-19 (P less then .05); compared with patients without liver injury, patients with liver injury had increased levels of white blood cell counts, neutrophils, CRP and CT score (P less then .05) and had a longer length of stay (P less then .05). Logistic regression analyses suggested that the extent of pulmonary lesions on CT was a predictor of liver function damage (P less then .05). CONCLUSIONS Liver injury is common in non-ICU hospitalized COVID-19 patients. It may be related to systemic inflammation. Intense monitoring and evaluation of liver function in patients with severe pulmonary imaging lesions should be considered. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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