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Mitophagy is known to contribute towards progression of Parkinson's disease. Korean red ginseng (KRG) is a widely used medicinal herb in East Asia, and recent studies have reported that KRG prevents 1-methyl-4-phenylpyridinium ion (MPP
)-induced cell death. This study was undertaken to investigate whether KRG suppresses MPP
-induced apoptosis and mitophagy.
SH-SY5Y cells were incubated with KRG for 24h, and subsequently exposed to MPP
. The MPP
-induced cell death was confirmed with the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. Changes in the structure and function of mitochondria were confirmed using mitotracker, MitoSOX red mitochondrial superoxide indicator, parkin, and phosphatase and tensin homolog deleted on chromosome ten-induced putative kinase 1 (PINK1) immunofluorescent staining. Western blotting was performed to evaluate the expression of apoptosis-related factors in whole cells, including Bax, Bcl-2 and cleaved caspase-3, and mitophagy-related factors in the mitochondrial fraction, including cytochrome c, parkin, PINK1, translocase of the outer membrane 20 (TOM20), p62 and Beclin 1.
MPP
induced cell death by cytochrome c release and caspase-3 activation; however, this effect was suppressed by KRG's regulation of the expressions of Bcl-2 and Bax. Moreover, MPP
exposure increased the mitochondrial expressions of parkin, PINK1, Beclin 1 and p62, and decreased TOM20, cytochrome c and Bcl-2 expressions. These MPP
-induced changes in the mitochondrial fraction were attenuated by treatment with KRG.
KRG effectively prevents MPP
-induced SH-SY5Y cell death by regulating cytochrome c release from mitochondria and PINK1/parkin-mediated mitophagy, through regulation of the Bcl-2 family.
KRG effectively prevents MPP+-induced SH-SY5Y cell death by regulating cytochrome c release from mitochondria and PINK1/parkin-mediated mitophagy, through regulation of the Bcl-2 family.Follicular lymphoma (FL) is the most common indolent lymphoma, accounting for 20%-25% of all non-Hodgkin's lymphomas (NHLs). It is a malignancy with variable biologic presentation and heterogeneous clinical outcomes. Several models incorporating clinical laboratory variables and molecular biomarkers are able to predict its prognosis, allowing to stratify patients into different risk groups. However, these prognostic scores should not be used to indicate first-line treatment or risk-adapted therapeutic recommendations. Over the past 5 years, progression of disease within 24 months (POD-24) of first-line chemo-immunotherapy has emerged as a robust adverse prognostic factor, capable of assessing overall survival and identifying high-risk patients with indication for more aggressive therapeutic approaches, such as consolidation based in autologous stem cell transplantation. read more It should be reinforced that POD-24 is not a baseline measurement, it is based on a post-treatment strategy, and is usually applied to patients with a high tumor burden. The identification of newly diagnosed patients at high risk for disease progression, particularly those with low tumor volume is still a challenge in the context of FL. link2 Therefore, the primary purpose of this review is to provide an overview of the main prognostic models validated to date for FL. Moreover, using these scores, which incorporate clinical and genetic variables, we aim to identify individuals with newly diagnosed FL, advanced disease, and low tumor burden with a high probability of progression or relapse within 24 months of first treatment. Thus, a decision regarding risk-adapted induction therapy could be better stablished for these subset of patients.
Non-typhoid Salmonella infection is a major agent of food-borne outbreaks as well as individual cases worldwide. However, few studies on drug-resistant Salmonella strains, especially those recovered from young children, are available. Therefore, we determined the prevalence and characteristics of cephalosporin-resistant Salmonella isolates in the south-west region of Korea over a five-year period.
Non-duplicate Salmonella clinical isolates were recovered from diarrhoeagenic patient specimens at 12 hospitals in Gwangju, Korea between January 2014 and December 2018. Antimicrobial susceptibility testing and molecular features of cephalosporin-resistant isolates were determined.
A total of 652 Salmonella isolates were collected and 48 cefotaxime-resistant Salmonella isolates (7.4%), that belonged to nine Salmonella serovars, were identified. These were S. Enteritidis, S. Typhimurium, S. I 4,[5],12i-, S. Virchow, S. Agona, S. Bareilly, S. Infantis, S. Newport, and S. Schleissheim. The prevalence rate increased from 5.3% in 2014 to 10.3% in 2018. S. Virchow (44.4%) showed significantly high resistant rate compared to the other serovars. PGFE genotyping revealed high genetic homogeneities among each Salmonella serovars, suggesting clonal dissemination of cephalosporin-resistant strains.
Progressive increases in carriage rates and the possibility of community outbreaks by cephalosporin-resistant Salmonella in young children may pose tangible public health threats.
Progressive increases in carriage rates and the possibility of community outbreaks by cephalosporin-resistant Salmonella in young children may pose tangible public health threats.
Viral respiratory infections are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and asthma. We conducted a multicenter prospective study to determine the differences in the spectrum of viruses between adults with asthma exacerbations and AECOPD and assessed the prevalence and impact of human rhinovirus (HRV)-C in adults, which is more pathogenic in children with asthma than other HRV species.
Nasopharyngeal and serum samples and clinical information were collected from 64 outpatients with adult asthma exacerbations and 44 outpatients with AECOPD between April 2018 and March 2020. Viral pathogens and HRV strains were identified from nasal samples by multiplex PCR and VP4/VP2 nested PCR.
Viral pathogens were identified in 31 patients with asthma exacerbations (48.4%) and 17 patients with AECOPD (38.6%). The most commonly detected viruses were HRV/enterovirus followed by human metapneumovirus (hMPV) in patients with asthma exacerbations, and hMPV followed by parainfluenza virus in patients with AECOPD. HRV-C was the HRV species most commonly associated with both asthma exacerbations and AECOPD. Clinical characteristics, baseline lung function, serum inflammatory chemokines, hospitalization, and systemic steroid use did not differ between HRV-C-positive patients and those positive for other HRV species.
Exacerbation-associated spectrum of viruses differed between adults with asthma exacerbations and AECOPD. HRV-C was the HRV species most often observed in adult asthma exacerbations and AECOPD, although it did not worsen patients' clinical outcomes relative to those of patients with other HRVs. Underlying disease-specific factors may be responsible for susceptibility to respiratory viruses.
UMIN-CTR UMIN000031934.
UMIN-CTR UMIN000031934.
An enhanced surveillance schedule has been proposed for cirrhotics with viral etiology, who are considered at extremely high-risk of hepatocellular carcinoma (HCC).
We compared the 3- and 6-months surveillance interval, evaluating cancer stage at diagnosis and patient survival.
Data of 777 HBV and HCV cirrhotic patients with HCC diagnosed under a 3-months (n=109, 3MS group) or a 6-months (n=668, 6MS group) surveillance were retrieved from the Italian Liver Cancer database. Survival in the 3MS group was considered as observed and adjusted for lead-time bias, and survival analysis was repeated after a propensity score matching.
The 3-months surveillance interval neither reduced the share of patients diagnosed outside the Milano criteria, nor increased their probability to receive curative treatments. The median survival of 6MS patients (55.0 months [45.9-64.0]) was not significantly different from the observed (47.0 months [35.0-58.9]; p=0.43) and adjusted (44.9 months [33.4-56.4]; p=0.30) survival of 3MS patients. A propensity score analysis confirmed the absence of a survival advantage for 3MS patients.
A tightening of surveillance schedule does not increase the diagnosis of early-stage tumors, the feasibility of curative treatments and the survival. Therefore, we should maintain the 6-months interval in the surveillance of viral cirrhotics.
A tightening of surveillance schedule does not increase the diagnosis of early-stage tumors, the feasibility of curative treatments and the survival. Therefore, we should maintain the 6-months interval in the surveillance of viral cirrhotics.Tumor mutational burden (TMB) is an emerging biomarker for the prediction of immunotherapy success in solid tumors. Gliomas, however, do not demonstrate a correlation between TMB and immunotherapy efficacy. Here, we discuss the potential factors influencing this discordance, focusing on the impact of neoantigen immunogenicity, clonality, expression, and presentation.Increasing evidence indicates that a mitochondria-specific stress response referred to as the 'mitochondrial unfolded protein response' (UPRmt) is activated to maintain mitochondrial integrity and support tumor growth. In this forum article, we discuss the recent advances and current challenges in therapeutically targeting UPRmt in cancer.Genome-scale genetic screens allow researchers to rapidly identify the genes and proteins that impact a particular phenotype of interest. In African trypanosomes, RNA interference (RNAi) knockdown screens have revealed mechanisms underpinning drug resistance, drug transport, prodrug metabolism, quorum sensing, genome replication, and gene expression control. RNAi screening has also been remarkably effective at highlighting promising potential antitrypanosomal drug targets. link3 The first ever RNAi library screen was implemented in African trypanosomes, and genome-scale RNAi screens and other related approaches continue to have a major impact on trypanosomatid research. Here, I review those impacts in terms of both discovery and translation.Breast cancer is a neoplastic disease and is a cause of cancer-related mortality for women. Among cellular and molecular regulators of the microenvironment, mast cells and vascular endothelial growth factor (VEGF), are correlated with tumor progression and prognosis in breast cancer. Clinical and experimental studies on breast cancer have revealed a marked correlation between increased angiogenesis, metastasization, and poorer prognosis. After a brief introduction on angiogenesis evidence and angiogenic factors role in different breast cancer subtypes, in this article, we have discerned the relationship between mast cell infiltration, angiogenesis, and tumor progression in human breast cancer with particular reference to the dual role of mast cells, in terms of both pro- or anti-tumoral activity and poor or good biomarker.The approval and subsequent reimbursement of CFTR modulator therapies from 2012 have provided a potential "game-changing" treatment for patients with cystic fibrosis (CF), especially among younger patients. We used HCUP-NIS and HCUP-KID data in 2006, 2009, 2012 and 2016 to compare the number of admissions, hospital charges/cost, length of stay (LOS) and other clinical outcomes between inpatient admissions aged over and below 20 with CF before and after the approval of CFTR therapies. We found the number of hospitalizations with CF dropped among those aged 0-20 but increased among those aged over 20. We found the average LOS and charges/costs increased among the former and decreased among the later. These findings support the hypothesis that modulator therapies have impacted on patterns of hospital care, contributing to a reduction in the number of young people treated in hospital albeit with an increase in their complexity relative to those aged over 20.
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