Sevoflurane Ameliorates Myocardial Cell Injury by Inducing Autophagy via the Deacetylation of LC3 by SIRT1

Misfolded and aberrant proteins have been found to be associated with myocardial cell injury. Thus, increased clearance of misfolded or aggregated proteins via autophagy might be a potential option in preventing myocardial cell injury. Sevoflurane may ameliorate myocardial cell injury by affecting sirtuin 1- (SIRT1-) mediated autophagy. Rat models with myocardial cell injury were induced by limb ischemia reperfusion. The model rats received different treatments: sevoflurane, nicotinamide, and autophagy inhibitor 3-methyladenine (3-MA). Autophagy was observed by SEM. The levels of SIRT1 and microtubule-associated protein 1A/1B-light chain 3 (LC3) were measured. Present findings demonstrated that limb ischemia reperfusion induced autophagy. Sevoflurane increased the level of SIRT1, which deacetylated LC3 and further increased autophagic rates. On the other hand, the autophagy was inhibited by sevoflurane and or the inhibitors of SIRT1 and LC3. Present results demonstrated a novel molecular mechanism by which sevoflurane induced autophagy by increasing the level of SIRT1 and reducing the acetylation of LC3

Epigenetic regulation of CD271, a potential cancer stem cell marker associated with chemoresistance and metastatic capacity.

Cancer stem cells (CSCs) are considered to be the cause of tumor initiation, metastasis and recurrence. Additionally, CSCs are responsible for the failure of chemotherapy and radiotherapy. The isolation and identification of CSCs is crucial for facilitating the monitoring, therapy or prevention of cancer. We aimed to identify esophageal squamous cell carcinoma (ESCC) stem-like cells, the epigenetic mechanism and identify novel biomarkers for targeting ESCC CSCs. Sixty-three paired ESCC tissues and adjacent non-cancerous tissues were included in this study. CD271, which was identified as the CSC marker for melanoma, was assessed using quantitative PCR (qPCR). Using flow cytometry, we isolated CD271+ cells comprising 7.5% of cancer cells from the KYSE70 cell line. Sphere formation and anchorage-independent growth were analyzed in CD271+ and CD271- cancer cells, respectively. qPCR was used to detect stem-related genes and CCK-8 was performed to analyze the sensitivity to chemotherapy in the two groups. Bisulfite genomic sequencing was used to analyze the methylation status. CD271 expression was significantly higher in ESCC tissues than in adjacent non-cancerous tissues. Compared with CD271- cancer cells, CD271+ cancer cells showed a higher ability of sphere and colony formation, a high level expression of stem-related gene, and resistance to chemotherapy. The expression of CD271 was induced by a demethylation agent. In conclusion, CD271+ ESCC cells possess stem-like properties. CD271 can potentially act as a prognostic marker for ESCC, whose expression is regulated epigenetically

Perioperative dynamic alterations in peripheral regulatory T and B cells in patients with hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Intratumoral and circulating regulatory T cells (Tregs) have been shown to be critical in the pathogenesis of hepatocellular carcinoma (HCC). However there is limited knowledge on the alterations of regulatory B cells (Bregs). We here investigated perioperative dynamic alterations of peripheral circulating Tregs and Bregs in HCC patients to reveal the relationship between regulatory lymphocytes and its clinical implications.</p> <p>Methods</p> <p>36 patients with HCC, 6 with chronic hepatitis B infection and 10 healthy donors were enrolled for this study. Frequencies of peripheral Tregs and Bregs were measured by flow cytometry with antibodies against CD4, CD25, CD127, CD19 and IL-10 before, and after radical surgery. Then, clinical informatics of HCC patients was achieved through Digital Evaluation Score System (DESS) for the assessment of disease severity. Finally, we analysed correlations between digitalized clinical features and kinetics of circulating regulatory lymphocytes.</p> <p>Results</p> <p>Level of circulating CD4⁺CD25⁺CD127^-Tregs in HCC patients was significantly lower than that in healthy donors and patients with chronic hepatitis B infection before surgery, but was increased after surgery. Preoperative level of CD19⁺IL-10⁺Bregs in HCC patients was also significantly lower than the other groups. However it dramatically was elevated right after surgery and remained elevated compared to controls (about 7 days after surgery, <it>P </it>= 0.04). Frequency of circulating Tregs was correlated with circulating leukocytes, ferritin, and clinical features suggesting tumor aggressiveness including portal vein thrombosis, hepatic vein involvement and advanced clinical stages. Frequency of circulating Bregs was associated with Hepatitis B e Antigen (HBeAg) and Hepatitis B virus (HBV) DNA copy number. In addition, DESS was significantly and positively correlated with other staging systems.</p> <p>Conclusion</p> <p>Frequencies of peripheral Tregs and Bregs in HCC patients increased after surgery. These results suggest that a postoperative combination of therapies against Tregs and Bregs may be beneficial for better outcome of HCC patients after resection.</p

Report drawn up on behalf of the Committee on Economic and Monetary Affairs on the possible loan from the OPEC countries to the Federal Republic of Germany and to France. EP Working Documents 1982-83, Document 1-284/82, 4 June 1982

Abstract Background Hand, foot, and mouth disease (HFMD) has become an emerging infectious disease in China in the last decade. There has been evidence that meteorological factors can influence the HFMD incidence, and understanding the mechanisms can help prevent and control HFMD. Methods HFMD incidence data and meteorological data in Minhang District, Shanghai were obtained for the period between 2009 and 2015. Distributed lag non-linear models (DLNMs) were utilized to investigate the impact of meteorological factors on HFMD incidence after adjusting for potential confounders of long time trend, weekdays and holidays. Results There was a non-linear relationship between temperature and HFMD incidence, the RR of 5th percentile compared to the median is 0.836 (95% CI: 0.671–1.042) and the RR of 95th percentile is 2.225 (95% CI: 1.774–2.792), and the effect of temperature varied across age groups. HFMD incidence increased with increasing average relative humidity (%) (RR = 1.009, 95% CI: 1.005–1.015) and wind speed (m/s) (RR = 1.197, 95% CI: 1.118–1.282), and with decreasing daily rainfall (mm) (RR = 0.992, 95% CI: 0.987–0.997) and sunshine hours (h) (RR = 0.966, 95% CI: 0.951–0.980). Conclusions There were significant relationships between meteorological factors and childhood HFMD incidence in Minhang District, Shanghai. This information can help local health agencies develop strategies for the control and prevention of HFMD under specific climatic conditions

Neutralization of IL- 10 produced by B cells promotes protective immunity during persistent HCV infection in humanized mice

Chronic HCV infection can lead to cirrhosis and is associated with increased mortality. Interleukin (IL)- 10- producing B cells (B10 cells) are regulatory cells that suppress cellular immune responses. Here, we aimed to determine whether HCV induces B10 cells and assess the roles of the B10 cells during HCV infection. HCV- induced B10 cells were enriched in CD19hi and CD1dhiCD5+ cell populations. HCV predominantly triggered the TLR2- MyD88- NF- κB and AP- 1 signaling pathways to drive IL- 10 production by B cells. In a humanized murine model of persistent HCV infection, to neutralize IL- 10 produced by B10 cells, mice were treated with pcCD19scFv- IL- 10R, which contains the genes coding the anti- CD19 single- chain variable fragment (CD19scFv) and the extracellular domain of IL- 10 receptor alpha chain (sIL- 10Ra). This treatment resulted in significant reduction of B10 cells in spleen and liver, increase of cytotoxic CD8+ T- cell responses against HCV, and low viral loads in infected humanized mice. Our results indicate that targeting B10 cells via neutralization of IL- 10 may offer a novel strategy to enhance anti- HCV immunotherapy.HCV predominantly triggers the TLR2- MyD88- NF- κB and AP- 1 signaling pathways to drive IL- 10 production by B cells. Neutralization of IL- 10 produced by B10 cells promotes anti- HCV immunity in a humanized murine model of persistent HCV infection. These results provide insight into a novel immunotherapy strategy for HCV treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162732/2/eji4736.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162732/1/eji4736_am.pd

Scopararanes C–G: New Oxygenated Pimarane Diterpenes from the Marine Sediment-Derived Fungus Eutypella scoparia FS26

Five new oxygenated pimarane diterpenes, named scopararanes C–G (1–5) were isolated from the culture of a marine sediment-derived fungus Eutypella scoparia FS26 obtained from the South China Sea. The structures of these compounds were established on the basis of extensive spectroscopic analysis. The absolute configurations of compounds 1–5, were determined by CD spectroscopic analysis and comparison with literature data. All isolated compounds (1–5) were evaluated for their cytotoxic activities against MCF-7, NCI-H460, and SF-268 tumor cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) method

Defining the threshold: triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio’s non-linear impact on tubular atrophy in primary membranous nephropathy

BackgroundHyperlipidemia is common in primary membranous nephropathy (PMN) patients, and tubular atrophy (TA) is an unfavorable prognostic factor. However, the correlation between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and TA is controversial. Therefore, our study aimed to investigate the association between the TG/HDL-C ratio and TA in PMN patients.MethodsWe conducted a cross-sectional study and collected data from 363 PMN patients at Shenzhen Second People’s Hospital from January 2008 to April 2023. The primary objective was to evaluate the independent correlation between the TG/HDL-C ratio and TA using binary logistic regression model. We used a generalized additive model along with smooth curve fitting and multiple sensitivity analyses to explore the relationship between these variables. Additionally, subgroup analyses were conducted to delve deeper into the results.ResultsOf the 363 PMN patients, 75 had TA (20.66%). The study population had a mean age of 46.598 ± 14.462 years, with 217 (59.78%) being male. After adjusting for sex, age, BMI, hypertension, history of diabetes, smoking, alcohol consumption, UPRO, eGFR, HB, FPG, and ALB, we found that the TG/HDL-C ratio was an independent risk factor for TA in PMN patients (OR=1.29, 95% CI: 1.04, 1.61, P=0.0213). A non-linear correlation was observed between the TG/HDL-C ratio and TA, with an inflection point at 4.25. The odds ratios (OR) on the left and right sides of this inflection point were 1.56 (95% CI: 1.17, 2.07) and 0.25 (95% CI: 0.04, 1.54), respectively. Sensitivity analysis confirmed these results. Subgroup analysis showed a consistent association between the TG/HDL-C ratio and TA, implying that factors such as gender, BMI, age, UPRO, ALB, hypertension and severe nephrotic syndrome had negligible effects on the link between the TG/HDL-C ratio and TA.ConclusionOur study demonstrates a non-linear positive correlation between the TG/HDL-C ratio and the risk of TA in PMN patients, independent of other factors. Specifically, the association is more pronounced when the ratio falls below 4.25. Based on our findings, it would be advisable to decrease the TG/HDL-C ratio below the inflection point in PMN patients as part of treatment strategies

The GECAM Real-Time Burst Alert System

Gravitational Wave High-energy Electromagnetic Counterpart All-sky Monitor (GECAM), consisting of two micro-satellites, is designed to detect gamma-ray bursts associated with gravitational-wave events. Here, we introduce the real-time burst alert system of GECAM, with the adoption of the BeiDou-3 short message communication service. We present the post-trigger operations, the detailed ground-based analysis, and the performance of the system. In the first year of the in-flight operation, GECAM was triggered by 42 GRBs. GECAM real-time burst alert system has the ability to distribute the alert within $\sim$1 minute after being triggered, which enables timely follow-up observations.Comment: 17 pages, 10 figures; Accepted for publication in RA

Validity and reliability of the Chinese version of the Normalization MeAsure Development(NoMAD)

Background: The Normalization MeAsure Development (NoMAD) is a brief quantitative tool based on the Normalization Process Theory (NPT), which can measure the implementation process of new technologies and complex interventions. The aim of our study was to translate and culturally adapt the NoMAD into Chinese, and to evaluate the psychometric properties of the Chinese version of NoMAD. Methods: According to the NoMAD translation guideline, we undertook forward translation, backward translation, and compared these translations to get a satisfactory result, then we performed cognitive interviews to achieve cross-culture adaptation. And the psychometric properties of the final version were evaluated among clinical nurses who used the pressure injuries management system via WeChat mini-program at a tertiary hospital in northwestern China. Results: A total of 258 nurses were enrolled in our study, and the response rate was 92.1%. The Cronbach’s alpha of four dimensions were as follow: Coherence (0.768), Cognitive Participation (0.904), Collective Action (0.820), and Reflexive Monitoring (0.808). The overall internal consistency was 0.941. The confirmatory factor analysis results showed a good fit for its theoretical structure (CFI = 0.924, TLI = 0.910, RMSEA = 0.0079, SRMSR = 0.046, χ2/df = 2.61). The item-level content validity index ranged from 0.857 to 1, and the scale-level content validity index was 0.95. There were positive correlations between four constructs scores and three general normalization scores. Conclusions: The Chinese version of NoMAD is a reliable and valid tool to evaluate the implementation process of innovations