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JAK2/STAT3 inside position involving arsenic-induced cell spreading: a systematic evaluation and meta-analysis.
BACKGROUND AND AIM As a result of its rapid spread in various countries around the world, on March 11, 2020, WHO issued an announcement of the change in coronavirus disease 2019 status from epidemic to pandemic disease. The virus that causes this disease is indicated originating from animals traded in a live animal market in Wuhan, China. Severe Acute Respiratory Syndrome Coronavirus 2 can attack lung cells because there are many conserved receptor entries, namely Angiotensin Converting Enzyme-2. The presence of this virus in host cells will initiate various protective responses leading to pneumonia and Acute Respiratory Distress Syndrome. This review aimed to provide an overview related to this virus and examine the body's responses and possible therapies. METHOD We searched PubMed databases for Severe Acute Respiratory Syndrome Coronavirus-2, Middle East respiratory syndrome-related coronavirus and Severe Acute Respiratory Syndrome Coronavirus. Full texts were retrieved, analyzed and developed into an easy-to-understand review. RESULTS We provide a complete review related to structure, origin, and how the body responds to this virus infection and explain the possibility of an immune system over-reaction or cytokine storm. We also include an explanation of how this virus creates modes of avoidance to evade immune system attacks. We further explain the therapeutic approaches that can be taken in the treatment and prevention of this viral infection. DZD9008 inhibitor CONCLUSION In summary, based on the structural and immune-evasion system of coronavirus, we suggest several approaches to treat the disease. It has been reported that frequent occurrence of COVID-19 infection in these patients is associated with low cytosolic pH. During virus infection, serum lactate dehydrogenase (LDH) level excessively rises. LDH is a cytosolic enzyme and the serum level increases as the cell break down. When anaerobic conditions develop, lactate formation increases from pyruvate. Cell pH is regulated by very complex mechanisms. When lactate increases in the extracellular area, this symporter carries lactate and H+ ion into the cell, and the intracellular pH quickly becomes acidic. Paradoxically, Na+/H+ exchanger activation takes place. While H+ ion is thrown out of the cell, Na+ and Ca+2 enter the cell. When Na+ and Ca+2 increase in the cell, the cells swell and die. Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor. Dapagliflozin has been reported to reduce lactate levels by various mechanisms. Also, it reduces oxygen consumption in tissues and causes the use of glucose in the aerobic pathway, thereby reducing lactate production. A lactate decrease in the environment reduces the activation of lactate/H+ symporter. Thus, the H ion pumping into the cell by this symporter is reduced and the cytosolic pH is maintained. Dapagliflozin also directly inhibits NHE. Thus, Na+ and Ca+2 flow to the cell are inhibited. Dapagliflozin provides the continuation of the structure and functions of the cells. Dapagliflozin can prevent the severe course of COVID-19 infection by preventing the lowering of cytosolic pH and reducing the viral load. INTRODUCTION External beam radiotherapy (EBRT) is actively used for hepatocellular carcinoma (HCC) treatment in clinical practice but has not got attention in several guidelines owing to the lack of high-level evidences. We evaluated HCC treatment guidelines from the radiation oncology perspective using the Appraisal of Guidelines for Research and Evaluation (AGREE II) model, to provide information to choose suitable guidelines and for future guidelines developments. METHODS Guidelines and consensuses for HCC management involving EBRT that have been published until May 2019 were included. Seven appraisers from 6 countries participated; all were radiation oncologists specialized in HCC. Guidelines were assessed using the AGREE II (December 2017 update), and we added an additional domain, "Radiotherapy Content," to evaluate the fidelity of evidence and participation of relevant specialists. Inconsistency among appraisers was evaluated, and standard deviations (SD) among the average scores of each domain were cabed in future guidelines. *National Cancer Comprehensive Network, European Association for the Study of the Liver, American Association for the Study of the Liver Disease, Korean Liver Cancer Study Group. BACKGROUND A phase I-II study to evaluate the feasibility and efficacy of intensified, primary radiotherapy (RT) for Locally Advanced Head and Neck Squamous Cell Carcinoma (LAHNSCC) employing dose escalation by hyperfractionation, acceleration of treatment time, concomitant chemotherapy and hypoxic modification. METHODS Patients with HPV/p16- LAHNSCC receiving primary hyperfractionated, accelerated RT, 76 Gy/56 fx, 10 fx/week for 5½ weeks, concomitant weekly cisplatin (40 mg/m2) and nimorazole (HART-CN) were included. Primary endpoint was locoregional failure (LRF). Secondary endpoints were overall survival (OS) and toxicity. RESULTS 50 patients received HART-CN from 2013 to 2017. Median age was 60 years. Most patients had stage IV hypo- or oropharynx cancer with a heavy smoking history. All oropharyngeal cancers were HPV/p16-negative. Ninety-eight percent of patients completed RT, but compliance to cisplatin and nimorazole was lower. Median observation time was 44 months. LRF was diagnosed in 10 patients. All LRFs were in the high-dose CTV. The 3-year actuarial LRF was 21%, and OS was 74%. The peak incidence of acute toxicity showed that 67% of patients experienced severe dysphagia, 61% severe mucositis, and 78% were equipped with feeding tubes. Late severe morbidity was seen in 7 of 29 recurrence-free patients with at least 3 years of followup, who presented with either severe dysphagia (n = 2), severe xerostomia (n = 1), severe fibrosis of the neck (n = 3) or osteoradionecrosis (n = 1). Three were still tube dependent. CONCLUSION HART-CN is feasible in patients with HPV/p16- LAHNSCC in good health. Although acute toxicity was pronounced, the proportion of patients with late toxicity was acceptable and outcome at 3 years encouraging. Ultrasound (US) is an important imaging modality in brachytherapy (BT). In particular for low-dose-rate (LDR) and high-dose-rate (HDR) prostate implants transrectal ultrasound (TRUS) is widespread. Besides the common use of US for prostate implants, US can also be applied in gynecological and anal cancer therapies as examples amongst others. The BRAPHYQS (BRAchytherapy PHYsics Quality assurance System) and UroGEC (urology) working groups of GEC-ESTRO (GEC Groupe Européen de Curiethérapie, committee of ESTRO European SocieTy for Radiotherapy & Oncology) elaborated upon guidelines describing quality assurance (QA) methods for US in BT. The total quality management (QM) for the unit includes acceptance testing, commissioning and periodic image testing. In 2008, the AAPM (American Association of Physicists in Medicine) published the TG (Task group) 128 report. Whereas the TG 128 focuses on US systems and prostate BT, the current recommendations also cover tests for stepping devices and include other interstitial or intracavitary treatment sites in BT, such as anal implants and gynecological BT. The recommendations presented herein do not replace regular maintenance for the US devices performed by the vendor. They are the QA of US in BT but are not sufficient for the whole maintenance of medical US devices. Moreover, national regulations and recommendations should also be followed. For the tests presented in this report tolerances or action limits are given. These recommendations explain practical test procedures of US devices in BT. They will help the clinics to perform a high level of quality in the use of US for BT in Europe. Early-onset Parkinson's disease-associated PINK1-Parkin signaling maintains mitochondrial health. Therapeutic approaches for enhancing PINK1-Parkin signaling present a potential strategy for treating various diseases caused by mitochondrial dysfunction. We report two chemical enhancers of PINK1-Parkin signaling, identified using a robust cell-based high-throughput screening system. These small molecules, T0466 and T0467, activate Parkin mitochondrial translocation in dopaminergic neurons and myoblasts at low doses that do not induce mitochondrial accumulation of PINK1. Moreover, both compounds reduce unfolded mitochondrial protein levels, presumably through enhanced PINK1-Parkin signaling. These molecules also mitigate the locomotion defect, reduced ATP production, and disturbed mitochondrial Ca2+ response in the muscles along with the mitochondrial aggregation in dopaminergic neurons through reduced PINK1 activity in Drosophila. Our results suggested that T0466 and T0467 may hold promise as therapeutic reagents in Parkinson's disease and related disorders. Direct conversion of carbon dioxide (CO2) to high-energy fuels and high-value chemicals is a fascinating sustainable strategy. For most of the current electrocatalysts for CO2 reduction, however, multi-carbon products are inhibited by large overpotentials and low selectivity. Herein, we exploit dispersed 3d transition metal dimers as spatially confined dual reaction centers for selective reduction of CO2 to liquid fuels. Various nitrogenated holey carbon monolayers are shown to be promising templates to stabilize these metal dimers and dictate their electronic structures, allowing precise control of the catalytic activity and product selectivity. By comprehensive first-principles calculations, we screen the suitable transition metal dimers that universally have high activity for ethanol (C2H5OH). Furthermore, remarkable selectivity for C2H5OH against other C1 and C2 products is found for Fe2 dimer anchored on C2N monolayer. The role of electronic coupling between the metal dimer and the carbon substrates is thoroughly elucidated. A circular-transcriptome-wide study has recently linked differential expression of circular RNAs (circRNAs) in brain tissue with Alzheimer's disease (AD). We aimed at replicating the major findings in an independent series of sporadic and familial AD. We also included cases with frontotemporal lobar degeneration (FTLD), comprising brain specimens with TDP-43 aggregates (FTLD-TDP43) and samples that presented Tau accumulation (FTLD-Tau). Using a quantitative polymerase chain reaction approach, we evaluated 8 circRNAs that surpassed the significant threshold in the former meta-analysis (circHOMER1, circDOCK1, circFMN1, circKCNN2, circRTN4, circMAN2A1, circMAP7, and circPICALM). Average expression changes between patients with AD and controls followed the same directions as previously reported. We also confirmed an exacerbated alteration in circRNA expression in the familial AD group compared with the sporadic forms. Two circRNAs (circHOMER1 and circKCNN2) also showed significant expression alterations in the group of FTLD-Tau and FTLD-TDP43, respectively. Overall, these results reinforce the conception that expression of circRNAs is different in AD, and also suggest a wider involvement of this particular class of RNA in other neurodegenerative dementias. Carbon monoxide (CO) produced by heme oxygenase-1 (HO-1) or delivered by CO-releasing molecules (CO-RMs) exerts anti-inflammatory action, a feature also exhibited by the nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the stress response. We have recently developed new hybrid molecules (HYCOs) consisting of CO-RMs conjugated to fumaric esters known to activate Nrf2/HO-1. Here we evaluated the biological activities of manganese (Mn) and ruthenium (Ru)-based HYCOs in human monocytes and keratinocytes in vitro as well as in vivo models of inflammation. The effects of HYCOs were compared to a) dimethyl fumarate (DMF), a known fumaric ester used in the clinic; b) a CO-RM alone; or c) the combination of the two compounds. Mn-HYCOs donated CO and up-regulated Nrf2/HO-1 in vitro more efficiently than Ru-HYCOs. However, irrespective of the metal, a strong reduction in anti-inflammatory markers in monocytes stimulated by LPS was observed with specific HYCOs. This effect was not observed with DMF, CO-RM alone or the combination of the two, indicating the enhanced potency of HYCOs compared to the separate entities.
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