Publications by authors named "Yuguo Chen"

130 Publications

Rapid Treatment with Intramuscular Magnesium Sulfate During Cardiopulmonary Resuscitation Does Not Provide Neuroprotection Following Cardiac Arrest.

Mol Neurobiol 2022 Jan 14. Epub 2022 Jan 14.

Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.

Brain injury is the most common cause of death for patients resuscitated from cardiac arrest. Magnesium is an attractive neuroprotective compound which protects neurons from ischemic injury by reducing neuronal calcium overload via NMDA receptor modulation and preventing calcium-induced mitochondrial permeability transition. Intramuscular (IM) delivery of MgSO during CPR has the potential to target these mechanisms within an early therapeutic window. We hypothesize that IM MgSO administrated during CPR could achieve therapeutic serum magnesium levels within 15 min after ROSC and improve neurologic outcomes in a rat model of asphyxial cardiac arrest. Male Long Evans rats were subjected to 8-min asphyxial cardiac arrest and block randomized to receive placebo, 107 mg/kg, 215 mg/kg, or 430 mg/kg MgSO IM at the onset of CPR. Serum magnesium concentrations increased rapidly with IM delivery during CPR, achieving twofold to fourfold increase by 15 min after ROSC in all magnesium dose groups. Rats subjected to cardiac arrest or sham surgery were block randomized to treatment groups for assessment of neurological outcomes. We found that IM MgSO during CPR had no effect on ROSC rate (p > 0.05). IM MgSO treatment had no statistically significant effect on 10-day survival with good neurologic function or hippocampal CA1 pyramidal neuron survival compared to placebo treatment. In conclusion, a single dose IM MgSO during CPR achieves up to fourfold baseline serum magnesium levels within 15 min after ROSC; however, this treatment strategy did not improve survival, recovery of neurologic function, or neuron survival. Future studies with repeated dosing or in combination with hypothermic targeted temperature management may be indicated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-021-02645-xDOI Listing
January 2022

Development and Validation of a Simple-to-Use Nomogram for Predicting In-Hospital Mortality in Patients With Acute Heart Failure Undergoing Continuous Renal Replacement Therapy.

Front Med (Lausanne) 2021 3;8:678252. Epub 2021 Nov 3.

Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, China.

Patients with acute heart failure (AHF) who require continuous renal replacement therapy (CRRT) have a high risk of in-hospital mortality. It is clinically important to screen high-risk patients using a model or scoring system. This study aimed to develop and validate a simple-to-use nomogram consisting of independent prognostic variables for the prediction of in-hospital mortality in patients with AHF undergoing CRRT. We collected clinical data for 121 patients with a diagnosis of AHF who underwent CRRT in an AHF unit between September 2011 and August 2020 and from 105 patients in the medical information mart for intensive care III (MIMIC-III) database. The nomogram model was created using a visual processing logistic regression model and verified using the standard method. Patient age, days after admission, lactic acid level, blood glucose concentration, and diastolic blood pressure were the significant prognostic factors in the logistic regression analyses and were included in our model (named D-GLAD) as predictors. The resulting model containing the above-mentioned five factors had good discrimination ability in both the training group (C-index, 0.829) and the validation group (C-index, 0.740). The calibration and clinical effectiveness showed the nomogram to be accurate for the prediction of in-hospital mortality in both the training and validation cohort when compared with other models. The in-hospital mortality rates in the low-risk, moderate-risk, and high-risk groups were 14.46, 40.74, and 71.91%, respectively. The nomogram allowed the optimal prediction of in-hospital mortality in adults with AHF undergoing CRRT. Using this simple-to-use model, the in-hospital mortality risk can be determined for an individual patient and could be useful for the early identification of high-risk patients. An online version of the D-GLAD model can be accessed at https://ahfcrrt-d-glad.shinyapps.io/DynNomapp/. www.ClinicalTrials.gov, identifier: NCT0751838.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2021.678252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595094PMC
November 2021

Corrigendum: Oseltamivir Improved Thrombocytopenia During Veno-Arterial Extracorporeal Membrane Oxygenation in Adults With Refractory Cardiac Failure: A Single-Center Retrospective Real-World Study.

Front Cardiovasc Med 2021 29;8:784904. Epub 2021 Oct 29.

Department of Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

[This corrects the article DOI: 10.3389/fcvm.2021.645867.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.784904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589771PMC
October 2021

Prevalence and related factors of do-not-resuscitate orders among in-hospital cardiac arrest patients.

Heart Lung 2021 Oct 29;51:9-13. Epub 2021 Oct 29.

Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine; Qilu Hospital of Shandong University, Jinan, China. Electronic address:

Purpose: Studies concerning do-not-resuscitate (DNR) orders in mainland China are rather scarce. We explored the prevalence and related factors of DNR orders among in-hospital cardiac arrest (IHCA) patients at a general tertiary hospital in mainland China.

Materials And Methods: We identified all IHCA patients hospital-wide between July 2019 and September 2020. Data regarding DNR status were collected from medical records. We investigated the frequency of DNR orders and explored the determinant factors of DNR establishment using logistic regression.

Results: A total of 1154 IHCA patients were included, 535 (46.4%) of whom established DNR orders. The following variables were independently associated with a higher DNR rate: female (OR 1.491; 95% CI 1.130-1.965), older age (OR 1.016; 95% CI 1.008-1.024), being a local resident (OR 1.790; 95% CI 1.344-2.383), pulmonary infection (OR 1.398; 95% CI 1052-1.859), respiratory insufficiency (OR 1.356; 95% CI 1.009-1.823), shock (OR 1.735; 95% CI 1.301-2.313), acute stroke (OR 1.821; 95% CI 1.235-2.686),neurological dysfunction (OR 1.527; 95% CI 1.149-2.028) and cancer (OR 3.316; 95% CI 2.461-4.468). Counterintuitively, patients with new-onset coronary artery disease (OR 0.592; 95% CI 0.419-0.837) were less likely to create DNR orders.

Conclusion: In mainland China, the DNR order signing rate is low, and the establishment of a DNR order is associated with demographics and comorbidity characteristics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hrtlng.2021.08.005DOI Listing
October 2021

Comparison of Safety and Efficacy Between Clopidogrel and Ticagrelor in Elderly Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

Front Pharmacol 2021 18;12:743259. Epub 2021 Oct 18.

Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China.

Dual antiplatelet therapy combining aspirin with a P2Y12 adenosine diphosphate receptor inhibitor is a therapeutic mainstay for acute coronary syndrome (ACS). However, the optimal choice of P2Y12 adenosine diphosphate receptor inhibitor in elderly (aged ≥65 years) patients remains controversial. We conducted a meta-analysis to compare the efficacy and safety of ticagrelor and clopidogrel in elderly patients with ACS. We comprehensively searched in Web of Science, EMBASE, PubMed, and Cochrane databases through 29 March, 2021 for eligible randomized controlled trials (RCTs) comparing the efficacy and safety of ticagrelor or clopidogrel plus aspirin in elderly patients with ACS. Four studies were included in the final analysis. A fixed effects model or random effects model was applied to analyze risk ratios (RRs) and hazard ratios (HRs) across studies, and I to assess heterogeneity. A total number of 4429 elderly patients with ACS were included in this analysis, of whom 2170 (49.0%) patients received aspirin plus ticagrelor and 2259 (51.0%) received aspirin plus clopidogrel. The ticagrelor group showed a significant advantage over the clopidogrel group concerning all-cause mortality (HR 0.78, 95% CI 0.63-0.96, I = 0%; RR 0.79, 95% CI 0.66-0.95, I = 0%) and cardiovascular death (HR 0.71, 95% CI 0.56-0.91, I = 0%; RR 0.76, 95% CI 0.62-0.94, I = 5%) but owned a higher risk of PLATO major or minor bleeding (HR 1.46, 95% CI 1.13-1.89, I = 0%; RR 1.40, 95% CI 1.11-1.76, I = 0%). Both the groups showed no significant difference regarding major adverse cardiovascular events (MACEs) (HR 1.06, 95% CI 0.68-1.65, I = 77%; RR 1.04, 95% CI 0.69-1.58, I = 77%). For elderly ACS patients, aspirin plus ticagrelor reduces cardiovascular death and all-cause mortality but increases the risk of bleeding. Herein, aspirin plus ticagrelor may extend lifetime for elderly ACS patients compared with aspirin plus clopidogrel. The optimal DAPT for elderly ACS patients may be a valuable direction for future research studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.743259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552409PMC
October 2021

Different Evolution Behaviors of Adhesion Force with Relative Humidity at Silica/Silica and Silica/Graphene Interfaces Studied using Atomic Force Microscopy.

Langmuir 2021 Nov 27;37(44):13075-13084. Epub 2021 Oct 27.

School of Mechanical and Electrical Engineering, Guangzhou University, Guangzhou 510006, China.

The influence of relative humidity (RH) on adhesion forces demands clarification. Adhesion forces at silica/silica and silica/graphene interfaces were measured on an atomic force microscope to investigate the evolution behaviors with RH and the contact time dependence at a certain RH. For the silica/silica interface, the adhesion force at a location by decreasing RH is independent of RH, but increases as a whole with RH both at a location and in the force volume mode by increasing RH. However, for the silica/graphene interface at a location, the adhesion force remains unchanged with RH as a whole by reducing RH and tends to decrease as a whole by increasing RH. In the force volume mode, the adhesion force at the silica/graphene interface is independent of RH. For the silica/silica interface, the adhesion force increases logarithmically with dwell time at a low RH and remains unchanged at a high RH. However, for the silica/graphene interface, the force is not dependent on RH at low and high RHs. The results can serve to further understand the mechanisms and behaviors of adhesion forces and promote the anti-adhesion design for small-scale silicon-based structures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.langmuir.1c02221DOI Listing
November 2021

4-Hydroxy-2-Nonenal Promotes Cardiomyocyte Necroptosis Stabilizing Receptor-Interacting Serine/Threonine-Protein Kinase 1.

Front Cell Dev Biol 2021 1;9:721795. Epub 2021 Oct 1.

Department of Emergency and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Necroptosis is a vital regulator of myocardial ischemia/reperfusion (MI/R) injury. Meanwhile, 4-hydroxy-2-nonenal (4-HNE) is abundantly increased during MI/R injury. However, whether 4-HNE induces cardiomyocyte necroptosis during MI/R remains unknown. To observe the relationship between 4-HNE and necroptosis during MI/R, C57BL/6 mice and aldehyde dehydrogenase 2-transgenic (ALDH2-Tg) mice were both exposed to left anterior descending artery ligation surgery to establish MI/R injury models. For further study, isolated mouse hearts and H9c2 cells were both treated with 4-HNE to elucidate the underlying mechanisms. Necroptosis and 4-HNE were both upregulated in I/R-injured hearts. Cardiomyocyte necroptosis was significantly decreased in I/R-injured hearts from ALDH2-Tg mice as compared with that of wild-type mice. studies showed that necroptosis was enhanced by 4-HNE perfusion in a time- and concentration-dependent manner. Knockdown of receptor-interacting serine/threonine-protein kinase 1 (RIP1) using small interfering RNA (siRNA) prevented 4-HNE-induced cardiomyocyte necroptosis, manifesting that RIP1 played a key role in the upregulation of cell necroptosis by 4-HNE. Further studies found that 4-HNE reduced the protein degradation of RIP1 by preventing K48-polyubiquitination of RIP1. 4-HNE contributes to cardiomyocyte necroptosis by regulating ubiquitin-mediated proteasome degradation of RIP1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.721795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517475PMC
October 2021

Lymphatics in the broken heart.

J Clin Invest 2021 10;131(20)

Department of Microbiology, Tumor and Cell Biology, Biomedicum, Karolinska Institutet, Stockholm, Sweden.

Cardiac lymphatics have emerged as a therapeutic target in cardiovascular diseases to limit myocardial edema and inflammation, notably after myocardial infarction (MI). While most experimental therapeutic approaches have focused on vascular endothelial growth factor C (VEGF-C) delivery, it remains uncertain to what degree the beneficial cardiac effects are related to lymphatic expansion in the heart. In this issue of the JCI, Keller, Lim, et al. reexamined the acute functional impact of endogenous cardiac lymphangiogenesis in the infarct zone after MI in mice. Their data, obtained by elegant comparisons of several complementary genetic mouse models, indicate that infarct expansion and left ventricular dilation and function after MI are unaffected by infarct lymphangiogenesis. This Commentary places the results into the context of previous findings. We believe these data will help further advance the research field of cardiac lymphatics to guide better clinical translation and benefit patients with ischemic heart disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI153448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516460PMC
October 2021

Fundamental Mechanisms of the Cell Death Caused by Nitrosative Stress.

Front Cell Dev Biol 2021 20;9:742483. Epub 2021 Sep 20.

Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China.

Nitrosative stress, as an important oxygen metabolism disorder, has been shown to be closely associated with cardiovascular diseases, such as myocardial ischemia/reperfusion injury, aortic aneurysm, heart failure, hypertension, and atherosclerosis. Nitrosative stress refers to the joint biochemical reactions of nitric oxide (NO) and superoxide (O ) when an oxygen metabolism disorder occurs in the body. The peroxynitrite anion (ONOO) produced during this process can nitrate several biomolecules, such as proteins, lipids, and DNA, to generate 3-nitrotyrosine (3-NT), which further induces cell death. Among these, protein tyrosine nitration and polyunsaturated fatty acid nitration are the most studied types to date. Accordingly, an in-depth study of the relationship between nitrosative stress and cell death has important practical significance for revealing the pathogenesis and strategies for prevention and treatment of various diseases, particularly cardiovascular diseases. Here, we review the latest research progress on the mechanisms of nitrosative stress-mediated cell death, primarily involving several regulated cell death processes, including apoptosis, autophagy, ferroptosis, pyroptosis, NETosis, and parthanatos, highlighting nitrosative stress as a unique mechanism in cardiovascular diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.742483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488117PMC
September 2021

High-Dose versus Standard-Dose Tigecycline Treatment of Secondary Bloodstream Infections Caused by Extensively Drug-Resistant : An Observational Cohort Study.

Infect Drug Resist 2021 18;14:3837-3848. Epub 2021 Sep 18.

Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, People's Republic of China.

Background: Extensively drug-resistant (XDR-AB) infections have become difficult to treat and are associated with a high mortality rate. Tigecycline is one of the most effective agents used to treat XDR-AB infections, but data from treating bloodstream infection (BSI) in standard dose do not look promising, because of its low plasma concentration. Secondary BSI with primary infection source may indicate tigecycline treatment with a higher dose. Currently, little is known about the application of high-dose tigecycline among patients with secondary BSI caused by XDR-AB. We aimed to investigate the outcomes for high-dose (HD) tigecycline treatment versus standard-dose (SD) treatment of these patients.

Methods: An observational cohort study was conducted at four university affiliated hospitals in mainland China. Adult inpatients who were confirmed as having secondary BSI caused by XDR-AB and received definitive tigecycline treatment were consecutively included. Patients who were treated with 50 mg every 12 h were defined as the SD group, and a twice dose was defined as the HD group.

Results: Of the enrolled patients, 63 received SD and 88 received HD tigecycline treatment. Patients in the two groups had similar with regard to baseline clinical conditions. The 30-day survival was affected by the source of the primary infection. Survival was significantly better in patients with non-pulmonary-infection-related BSI than in patients with pulmonary-infection-related BSI. Multivariate Cox regression confirmed that HD had a protective effect only observed in patients with non-pneumonia-related BSI.

Conclusion: A tigecycline dose that is twice its standard dose is better for the treatment of XDR-AB infection only in BSI associated with non-pulmonary infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IDR.S322803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457649PMC
September 2021

Osthole Attenuates Bleomycin-Induced Pulmonary Fibrosis by Modulating NADPH Oxidase 4-Derived Oxidative Stress in Mice.

Oxid Med Cell Longev 2021 4;2021:3309944. Epub 2021 Sep 4.

Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, China.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by the extensive accumulation of myofibroblasts and collagens. However, the exact mechanism that underlies this condition is unclear. Growing evidence suggests that NADPH oxidases (NOXs), especially NOX4-derived oxidative stress, play an important role in the development of lung fibrosis. Bleomycin (BLM) is a tumor chemotherapeutic agent, which has been widely employed to establish IPF animal models. Osthole (OST) is an active constituent of the fruit of . Here, we used an in vivo mouse model and found that OST suppressed BLM-induced body weight loss, lung injury, pulmonary index increase, fibroblast differentiation, and pulmonary fibrosis. OST also significantly downregulated BLM-induced NOX4 expression and oxidative stress in the lungs. In vitro, OST could inhibit TGF-1-induced Smad3 phosphorylation, differentiation, proliferation, collagen synthesis, NOX4 expression, and ROS generation in human lung fibroblasts in a concentration-dependent manner. Moreover, NOX4 overexpression could prevent the above effects of OST. We came to the conclusion that OST could significantly attenuate BLM-induced pulmonary fibrosis in mice, via the mechanism that involved downregulating TGF-1/NOX4-mediated oxidative stress in lung fibroblasts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/3309944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437590PMC
September 2021

Complete genome sequence of a novel mitovirus from the phytopathogenic fungus Fusarium oxysporum.

Arch Virol 2021 Nov 8;166(11):3211-3216. Epub 2021 Sep 8.

Key Laboratory for Green Preservation and Control of Tobacco Diseases and Pest in Huanghuai Growing Area, Institute of Tobacco, Henan Academy of Agricultural Sciences, No. 116, Garden road, Jingshui District, Zhengzhou, 450002, Henan Province, People's Republic of China.

Fusarium oxysporum is a cosmopolitan plant pathogen that causes fusarium wilt and fusarium root rot in many economically important crops. There is still limited information about mycoviruses that infect F. oxysporum. Here, a novel mitovirus tentatively named "Fusarium oxysporum mitovirus 1" (FoMV1) was identified in F. oxysporum strain B2-10. The genome of FoMV1 is 2,453 nt in length with a predicted AU content of 71.6% and contains one large open reading frame (ORF) using the fungal mitochondrial genetic code. The ORF putatively encodes an RNA-dependent RNA polymerase (RdRp) of 723 aa with a molecular mass of 84.98 kDa. The RdRp domain of FoMV1 shares 29.01% to 68.43% sequence identity with the members of the family Mitoviridae. Phylogenetic analysis further suggested that FoMV1 is a new member of a distinct species in the genus Mitovirus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00705-021-05210-yDOI Listing
November 2021

Transmission of SARS-CoV-2 during air travel: a descriptive and modelling study.

Ann Med 2021 12;53(1):1569-1575

Emergency Department, Qilu Hospital, Shandong University, Jinan, China.

Objectives: To explore the potential of SARS-CoV-2 spread during air travel and the risk of in-flight transmission.

Methods: We enrolled all passengers and crew suspected of being infected with SARS-CoV-2, who bounded for Beijing on international flights. We specified the characteristics of all confirmed cases of COVID-19 infection and utilised Wells-Riley equation to estimate the infectivity of COVID-19 during air travel.

Results: We screened 4492 passengers and crew with suspected COVID-19 infection, verified 161 confirmed cases (mean age 28.6 years), and traced two confirmed cases who may have been infected in the aircraft. The estimated infectivity was 375 quanta/h (range 274-476), while the effective infectivity was only 4 quanta/h (range 2-5). The risk of per-person infection during a 13 h air travel in economy class was 0.56‰ (95% CI 0.41‰-0.72‰).

Conclusion: We found that the universal use of face masks on the flight, together with the plane's ventilation system, significantly decreased the infectivity of COVID-19.KEY MESSAGESThe COVID-19 pandemic is changing the lifestyle in the world, especially air travel which has the potential to spread SARS-CoV-2.The universal use of face masks on the flight, together with the plane's ventilation system, significantly decreased the infectivity of COVID-19 on an aircraft.Our findings suggest that the risk of infection in aircraft was negligible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07853890.2021.1973084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409939PMC
December 2021

Oseltamivir Improved Thrombocytopenia During Veno-Arterial Extracorporeal Membrane Oxygenation in Adults With Refractory Cardiac Failure: A Single-Center Retrospective Real-World Study.

Front Cardiovasc Med 2021 26;8:645867. Epub 2021 Jul 26.

Qilu Hospital, Shandong University, Jinan, China.

Severe thrombocytopenia is a common complication of extracorporeal membrane oxygenation (ECMO). Oseltamivir can be used to treat infection-associated thrombocytopenia. To evaluate the effect of oseltamivir on attenuating severe thrombocytopenia during ECMO. This was a single-center real-world study in critically ill patients supported with venous-arterial extracorporeal membrane oxygenation (VA-ECMO). Patients suspected or confirmed with influenza received oseltamivir according to the Chinese guidelines. Thrombocytopenia and survival were compared between the oseltamivir-treated and untreated group. The factors associated with survival were analyzed by multivariable Cox analysis. A total of 82 patients were included. All patients developed thrombocytopenia after initiating VA-ECMO. Twenty-three patients received oseltamivir (O group), and 59 did not use oseltamivir (O group). During the first 8 days after VA-ECMO initiation, the platelet count in the O group was higher than that in the O group (all < 0.05). The patients in the O group had a higher median nadir platelet count (77,000/μl, 6,000-169,000/μl) compared with the O group (49,000/μl, 2,000-168,000/μl; = 0.04). A nadir platelet count of <50,000/μl was seen in 26% of the patients in the O group, compared with 53% in the O group ( = 0.031). No significant difference in survival from cardiac failure was seen between the O and O group (48 vs. 56%, = 0.508). The Sequential Organ Failure Assessment (SOFA) score on initiation of VA-ECMO were independently associated with survival (OR = 1.12, 95% confidence interval (95% CI): 1.02-1.22, = 0.015). Oseltamivir could ameliorate VA-ECMO-related thrombocytopenia. These findings suggested the prophylactic potential of oseltamivir on severe thrombocytopenia associated with the initiation of VA-ECMO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.645867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349981PMC
July 2021

Aldehyde dehydrogenase 2 protects against acute kidney injury by regulating autophagy via the Beclin-1 pathway.

JCI Insight 2021 08 9;6(15). Epub 2021 Aug 9.

The mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2) catalyzes the detoxification of acetaldehyde and endogenous lipid aldehydes. Approximately 40% of East Asians, accounting for 8% of the human population, carry the E504K mutation in ALDH2 that leads to accumulation of toxic reactive aldehydes and increases the risk for cardiovascular disease, cancer, and Alzheimer disease, among others. However, the role of ALDH2 in acute kidney injury (AKI) remains poorly defined and is therefore the subject of the present study using various cellular and organismal sources. In murine models, in which AKI was induced by either the contrast agent iohexol or renal ischemia/reperfusion, KO, activation/overexpression of ALDH2 were associated with increased and decreased renal injury, respectively. In murine renal tubular epithelial cells (RTECs), ALDH2 upregulated Beclin-1 expression, promoted autophagy activation, and eliminated ROS. In vivo and in vitro, both 3-MA and Beclin-1 siRNAs inhibited autophagy and abolished ALDH2-mediated renoprotection. In mice with iohexol-induced AKI, ALDH2 knockdown in RTECs using AAV-shRNA impaired autophagy activation and aggravated renal injury. In human renal proximal tubular epithelial HK-2 cells exposed to iohexol, ALDH2 activation potentiated autophagy and attenuated apoptosis. In mice with AKI induced by renal ischemia/reperfusion, ALDH2 overexpression or pretreatment regulated autophagy mitigating apoptosis of RTECs and renal injury. In summary, our data collectively substantiate a critical role of ALDH2 in AKI via autophagy activation involving the Beclin-1 pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.138183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410052PMC
August 2021

First Report of Root Rot of Tobacco Caused by Fusarium brachygibbosum in China.

Plant Dis 2021 May 18. Epub 2021 May 18.

Xuchang, China;

Tobacco (Nicotiana tabacum L.) is an important cash crop in China, with an estimated production of 2.2 million tons every year (Berbeć and Matyka, 2020). In June 2020, a root rot disease was observed on tobacco (cv. Zhongyan 100) in four surveyed counties (Mianchi, Lushi, Duguan and Lingbao) in Sanmenxia. Diseased plants exhibited leaf chlorosis and purplish to brown vascular discoloration of stem, taproot and lateral roots. The disease incidence ranged from 15% to 40% in 11 surveyed fields, 36.7 ha in total. Twenty five diseased tissues were surface sterilized in 75% ethanol and placed on potato dextrose agar (PDA) medium. Fifteen single-spore isolates were obtained from 25 diseased tissue samples. All cultures growing on PDA had white colonies with abundant aerial mycelia initially, turning into yellow to orange in the center and produced red pigmentation after seven days of growth. The 7-day-old cultures grown on carnation leaf agar (CLA) produced macroconidia that were curved with 3-5 septa, had wide central cells, slightly pointy apex, and measured 17.0-45.9 μm long×3.0-4.6 μm wide (n=50). The microconidia formed on CLA were slightly curved, ovoid with zero to two septa, measuring 5.4-15.5 μm long×2.0-3.2 μm wide (n=50). Spherical chlamydospores (7.58-13.52 μm; n=50) were terminal or intercalary, single or in chains. Such characteristics were typical of Fuarium brachygibbosum (Tirado-Ramírez et al. 2018). DNA from one representative single-spore isolate (MC1) was extracted, and the translation elongation factor 1-alpha (EF1-α), RNA polymerase I largest subunit (RPB1) and second largest subunit (RPB2) genes were amplified with primers EF1/EF2, F5/G2R and RPB2F/R respectively (O'Donnell et al. 1998, 2010), and sequenced. Sequences were submitted to GenBank under accession numbers MT947796 (EF1-α), MW679536 (RPB1) and MW430664 (RPB2). The consensus sequences showed 99.70%, 99.94% and 100% identity to the sequences of F. brachygibbosum strain NRRL 34033 (accession no. GQ505418.1, HM347172.1 and GQ505482.1, Wang et al 2021). Morphological and molecular results confirmed this species as F. brachygibbosum (Al-Mahmooli, et al., 2013, Rentería -Martínez, et al., 2018). Pathogenicity tests were performed on tobacco seedlings grown on autoclaved tobacco specific substrate (Tobacco specific matrix, Ainong Biotechnology Co. Ltd, China). Healthy six-leaf stage tobacco seedlings (n=30; Zhongyan 100) were inoculated by placing 7-days old wheat seed (15 seeds per plant) infested with MC1 around the root. Thirty seedlings inoculated with sterile wheat seeds served as controls. All the plants were maintained in a growth chamber at 25±0.5℃ and 70% relative humidity. The assay was conducted three times. Typical symptoms of foliage chlorosis and root browning were observed 7-14 days after inoculation. The pathogen was reisolated from the necrotic tissue from all inoculated seedlings and was identified by sequencing partial EF1-α and RPB2 genes. Control plants remained asymptomatic and no pathogen was recovered from the control plants. Fusarium brachygibbosum is known as a pathogen of grains and cash crops in China (Shan, et al., 2017, Xia, et al., 2018). To our knowledge, this is the first report of F. brachygibbosum causing root rot on tobacco. We believe that our results will help to better understand rhizome fungal diseases affecting tobacco production in China. Acknowledgements: Funding was provided by the Science and Technology Project of Henan Provincial Tobacco Company (2020410000270012), Independent Innovation Project of Hennan Academy of Agricultural Sciences (2020ZC18) and Research and Development project of Henan Academy of Agricultural Sciences (2020CY010). References: Al-Mahmooli, I. H., et al. 2013. Plant Dis. 97:687; https://doi.org/10.1094/PDIS-09-12-0828-PDN Berbeć A. K. and Matyka M. 2020. Agric. 10(11), 551; https://doi.org/10.3390/agriculture10110551 O'Donnell, K., et al. 1998. P. Natl. Acad. Sci. USA. 95(5):2044-2049; https://doi.org/10.1073/pnas.95.5.2044 O'Donnell, K., et al. 2010. J. Clin. Microbiol. 48(10)3708-3718; https://doi.org/10.1128/JCM.00989-10 Rentería -Martínez M.E., et al. 2018. Mex. J. of Phytopathol. 36(2):1-23; https://doi.org/10.18781/R.MEX.FIT.1710-1 Shan, L. Y., et al. 2017. Plant Dis. 101:837; https://doi.org/10.1094/PDIS-10-16-1465-PDN Tirado-Ramírez, M. A., et al. 2018. Plant Dis. 103; https://doi.org/10.1094/PDIS-04-18-0710-PDN Wang, S., et al. 2021. Plant Dis. 2021 Jan 6. doi: 10.1094/PDIS-05-20-0941-PDN. Epub ahead of print. PMID: 33406862. Xia, B., et al. 2018. Plant Dis. 102(11):2372; https://doi.org/10.1094/PDIS-12-17-1939-PDN The author(s) declare no conflict of interest.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1094/PDIS-01-21-0077-PDNDOI Listing
May 2021

Colonization With Extensively Drug-Resistant and Prognosis in Critically Ill Patients: An Observational Cohort Study.

Front Med (Lausanne) 2021 30;8:667776. Epub 2021 Apr 30.

Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China.

is one of the most frequently isolated opportunistic pathogens in intensive care units (ICUs). Extensively drug-resistant (XDR-AB) strains lack susceptibility to almost all antibiotics and pose a heavy burden on healthcare institutions. In this study, we evaluated the impact of XDR-AB colonization on both the short-term and long-term survival of critically ill patients. We prospectively enrolled patients from two adult ICUs in Qilu Hospital of Shandong University from March 2018 through December 2018. Using nasopharyngeal and perirectal swabs, we evaluated the presence of XDR-AB colonization. Participants were followed up for 6 months. The primary endpoints were 28-day and 6-month mortality after ICU admission. The overall survival rate was estimated by the Kaplan-Meier method. We identified risk factors associated with 28-day and 6-month mortality using the logistic regression model and a time-dependent Cox regression model, respectively. Out of 431 patients, 77 were colonized with XDR-AB. Based on the Kaplan-Meier curve results, the overall survival before 28 days did not differ by colonization status; however, a significantly lower overall survival rate was obtained at 6 months in colonized patients. Univariate and multivariate analysis results confirmed that XDR-AB colonization was not associated with 28-day mortality, but was an independent risk factor of lower overall survival at 6 months (HR = 1.749, 95% CI = 1.174-2.608). XDR-AB colonization has no effect on short-term overall survival, but is associated with lower long-term overall survival in critically ill patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2021.667776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119758PMC
April 2021

Epidemiological and clinical characteristics of imported cases of COVID-19: a multicenter study.

BMC Infect Dis 2021 May 3;21(1):406. Epub 2021 May 3.

Emergency Department, Qilu Hospital, Shandong University, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Jinan, Shandong, 250012, China.

Background: The coronavirus disease 2019 (COVID-19) pandemic continues to expand. Herein, we report the epidemiological and clinical features of 478 patients with confirmed COVID-19 from a multicenter study conducted in four cities in China excluding Wuhan.

Methods: A total of 478 patients transferred by emergency medical services to designated hospitals in four major cities in China (Beijing, Chongqing, Jinan, and Nanning) were enrolled. We compared the characteristics of imported and indigenous cases and calculated the frequencies of fatal, severe, mild, and asymptomatic disease. The results were used to generate a pyramid of COVID-19 severity.

Results: The mean age of patients with COVID-19 was 46.9 years and 49.8% were male. The most common symptoms at onset were fever (69.7%), cough (47.5%), fatigue (24.5%), dyspnea (8.4%), and headache (7.9%). Most cases (313, 65.5%) were indigenous, while 165 (34.5%) were imported. Imported cases dominated during the early stages of the pandemic, but decreased from 1 February 2020 as indigenous cases rose sharply. Compared with indigenous cases, imported cases differed significantly in terms of sex (P = 0.002), severity of disease (P = 0.006), occurrence of fever (P < 0.001), family clustering (P < 0.001), history of contact (P < 0.001), and primary outcome (P < 0.001).

Conclusions: Within the population studied, imported cases had distinct characteristics from those of indigenous cases, with lower fatality rates and higher discharge rates. New infections shifted from imported cases to local infection gradually, and overall infections have declined to a low level. We suggest that preventing import of cases and controlling spread within local areas can help prevent SARS-CoV-2 infection spread.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-021-06096-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090926PMC
May 2021

Inferring the Number of Attributes for the Exploratory DINA Model.

Psychometrika 2021 03 22;86(1):30-64. Epub 2021 Mar 22.

Department of Statistics, University of Illinois at Urbana-Champaign, 725 South Wright Street, Champaign, IL , 61820, USA.

Diagnostic classification models (DCMs) are widely used for providing fine-grained classification of a multidimensional collection of discrete attributes. The application of DCMs requires the specification of the latent structure in what is known as the [Formula: see text] matrix. Expert-specified [Formula: see text] matrices might be biased and result in incorrect diagnostic classifications, so a critical issue is developing methods to estimate [Formula: see text] in order to infer the relationship between latent attributes and items. Existing exploratory methods for estimating [Formula: see text] must pre-specify the number of attributes, K. We present a Bayesian framework to jointly infer the number of attributes K and the elements of [Formula: see text]. We propose the crimp sampling algorithm to transit between different dimensions of K and estimate the underlying [Formula: see text] and model parameters while enforcing model identifiability constraints. We also adapt the Indian buffet process and reversible-jump Markov chain Monte Carlo methods to estimate [Formula: see text]. We report evidence that the crimp sampler performs the best among the three methods. We apply the developed methodology to two data sets and discuss the implications of the findings for future research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11336-021-09750-9DOI Listing
March 2021

Scoparone alleviates Ang II-induced pathological myocardial hypertrophy in mice by inhibiting oxidative stress.

J Cell Mol Med 2021 03 9;25(6):3136-3148. Epub 2021 Feb 9.

Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, China.

Long-term poorly controlled myocardial hypertrophy often leads to heart failure and sudden death. Activation of ras-related C3 botulinum toxin substrate 1 (RAC1) by angiotensin II (Ang II) plays a pivotal role in myocardial hypertrophy. Previous studies have demonstrated that scoparone (SCO) has beneficial effects on hypertension and extracellular matrix remodelling. However, the function of SCO on Ang II-mediated myocardial hypertrophy remains unknown. In our study, a mouse model of myocardial hypertrophy was established by Ang II infusion (2 mg/kg/day) for 4 weeks, and SCO (60 mg/kg bodyweight) was administered by gavage daily. In vitro experiments were also performed. Our results showed that SCO could alleviate Ang II infusion-induced cardiac hypertrophy and fibrosis in mice. In vitro, SCO treatment blocks Ang II-induced cardiomyocyte hypertrophy, cardiac fibroblast collagen synthesis and differentiation to myofibroblasts. Meanwhile, we found that SCO treatment blocked Ang II-induced oxidative stress in cardiomyocytes and cardiac fibroblasts by inhibiting RAC1-GTP and total RAC1 in vivo and in vitro. Furthermore, reactive oxygen species (ROS) burst by overexpression of RAC1 completely abolished SCO-mediated protection in cardiomyocytes and cardiac fibroblasts in vitro. In conclusion, SCO, an antioxidant, may attenuate Ang II-induced myocardial hypertrophy by suppressing of RAC1 mediated oxidative stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.16304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957216PMC
March 2021

Efficacy and tolerability of bevacizumab in patients with severe Covid-19.

Nat Commun 2021 02 5;12(1):814. Epub 2021 Feb 5.

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, 17177, Sweden.

On the basis of Covid-19-induced pulmonary pathological and vascular changes, we hypothesize that the anti-vascular endothelial growth factor (VEGF) drug bevacizumab might be beneficial for treating Covid-19 patients. From Feb 15 to April 5, 2020, we conducted a single-arm trial (NCT04275414) and recruited 26 patients from 2-centers (China and Italy) with severe Covid-19, with respiratory rate ≥30 times/min, oxygen saturation ≤93% with ambient air, or partial arterial oxygen pressure to fraction of inspiration O ratio (PaO/FiO) >100 mmHg and ≤300 mmHg, and diffuse pneumonia confirmed by chest imaging. Followed up for 28 days. Among these, bevacizumab plus standard care markedly improves the PaO/FiO ratios at days 1 and 7. By day 28, 24 (92%) patients show improvement in oxygen-support status, 17 (65%) patients are discharged, and none show worsen oxygen-support status nor die. Significant reduction of lesion areas/ratios are shown in chest computed tomography (CT) or X-ray within 7 days. Of 14 patients with fever, body temperature normalizes within 72 h in 13 (93%) patients. Relative to comparable controls, bevacizumab shows clinical efficacy by improving oxygenation and shortening oxygen-support duration. Our findings suggest bevacizumab plus standard care is highly beneficial for patients with severe Covid-19. Randomized controlled trial is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-21085-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864918PMC
February 2021

Inhibition of adenosine kinase attenuates myocardial ischaemia/reperfusion injury.

J Cell Mol Med 2021 03 1;25(6):2931-2943. Epub 2021 Feb 1.

Department of Emergency and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Increased adenosine helps limit infarct size in ischaemia/reperfusion-injured hearts. In cardiomyocytes, 90% of adenosine is catalysed by adenosine kinase (ADK) and ADK inhibition leads to higher concentrations of both intracellular adenosine and extracellular adenosine. However, the role of ADK inhibition in myocardial ischaemia/reperfusion (I/R) injury remains less obvious. We explored the role of ADK inhibition in myocardial I/R injury using mouse left anterior ligation model. To inhibit ADK, the inhibitor ABT-702 was intraperitoneally injected or AAV9 (adeno-associated virus)-ADK-shRNA was introduced via tail vein injection. H9c2 cells were exposed to hypoxia/reoxygenation (H/R) to elucidate the underlying mechanisms. ADK was transiently increased after myocardial I/R injury. Pharmacological or genetic ADK inhibition reduced infarct size, improved cardiac function and prevented cell apoptosis and necroptosis in I/R-injured mouse hearts. In vitro, ADK inhibition also prevented cell apoptosis and cell necroptosis in H/R-treated H9c2 cells. Cleaved caspase-9, cleaved caspase-8, cleaved caspase-3, MLKL and the phosphorylation of MLKL and CaMKII were decreased by ADK inhibition in reperfusion-injured cardiomyocytes. X-linked inhibitor of apoptosis protein (XIAP), which is phosphorylated and stabilized via the adenosine receptors A2B and A1/Akt pathways, should play a central role in the effects of ADK inhibition on cell apoptosis and necroptosis. These data suggest that ADK plays an important role in myocardial I/R injury by regulating cell apoptosis and necroptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.16328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957171PMC
March 2021

Late Stent Thrombosis After Drug-Coated Balloon Coronary Angioplasty for In-Stent Restenosis.

Int Heart J 2021 Jan 16;62(1):171-174. Epub 2021 Jan 16.

Department of Emergency and Chest Pain Center, Cheeloo College of Medicine, Qilu Hospital of Shandong University.

A 41-year-old woman with chest pain for 6 hours was admitted to our chest pain center, presenting with acute myocardial infarction. Coronary angiography showed acute total occlusion in the proximal left anterior descending artery due to late stent thrombosis. After thrombus aspiration and intracoronary administration of 0.5 mg tirofiban, repeated angiography showed that no obvious residual stenosis remained. The patient underwent drug-coated balloon angioplasty 69 days ago and was then administered dual antiplatelet treatment (aspirin and clopidogrel) uninterruptedly. Genetic testing found that both cytochrome P450 2C19 (CYP2C19) (G681A) and glycoprotein Ia (GPIa) (C807T, G873A) were hybrid mutant types, demonstrating that the patient was possibly resistant to clopidogrel and aspirin simultaneously. Thus, clopidogrel was replaced by ticagrelor and no more cardiovascular adverse events occurred during the 2-year follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1536/ihj.20-309DOI Listing
January 2021

Current Evidence of Interleukin-6 Signaling Inhibitors in Patients With COVID-19: A Systematic Review and Meta-Analysis.

Front Pharmacol 2020 15;11:615972. Epub 2020 Dec 15.

Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, China.

Interleukin-6 (IL-6) is known to be detrimental in coronavirus disease 2019 (COVID-19) because of its involvement in driving cytokine storm. This systematic review and meta-analysis aimed to assess the safety and efficacy of anti-IL-6 signaling (anti-IL6/IL-6R/JAK) agents on COVID-19 based on the current evidence. Studies were identified through systematic searches of PubMed, EMBASE, ISI Web of Science, Cochrane library, ongoing clinical trial registries (clinicaltrials.gov), and preprint servers (medRxiv, ChinaXiv) on August 10, 2020, as well as eligibility checks according to predefined selection criteria. Statistical analysis was performed using Review Manager (version 5.3) and STATA 12.0. Thirty-one studies were included in the pooled analysis of mortality, and 12 studies were identified for the analysis of risk of secondary infections. For mortality analysis, 5630 COVID-19 cases including 2,132 treated patients and 3,498 controls were analyzed. Anti-IL-6 signaling agents plus standard of care (SOC) significantly decreased the mortality rate compared to SOC alone (pooled OR = 0.61, 95% CI 0.45-0.84, = 0.002). For the analysis of secondary infection risk, 1,624 patients with COVID-19 including 639 treated patients and 985 controls were included, showing that anti-IL-6 signaling agents did not increase the rate of secondary infections (pooled OR = 1.21, 95% CI 0.70-2.08, = 0.50). By contrast, for patients with critical COVID-19 disease, anti-IL-6 signaling agents failed to reduce mortality compared to SOC alone (pooled OR = 0.75, 95% CI 0.42-1.33, = 0.33), but they tended to increase the risk of secondary infections (pooled OR = 1.85, 95% CI 0.95-3.61, = 0.07). A blockade of IL-6 signaling failed to reduce the mechanical ventilation rate, ICU admission rate, or elevate the clinical improvement rate. IL-6 signaling inhibitors reduced the mortality rate without increasing secondary infections in patients with COVID-19 based on current studies. For patients with critical disease, IL-6 signaling inhibitors did not exhibit any benefit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.615972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769953PMC
December 2020

Aldehyde dehydrogenase 2 protects against sympathetic excitation-induced cardiac fibrosis.

Biochem Biophys Res Commun 2020 12 24;533(4):1427-1434. Epub 2020 Oct 24.

Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, China; Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Jinan, China; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China. Electronic address:

Sympathetic stimulated-cardiac fibrosis imposes great significance on both disease progression and survival in the pathogenesis of many cardiovascular diseases. However, there are few effective therapies targeting it clinically. The cardioprotective effect of aldehyde dehydrogenase 2 (ALDH2) has been explored in many pathological conditions, whether it can exert benefit effects on chronic sympathetic stimulus-induced cardiac fibrosis remains unclear. In this study, we determined to explore the role of ALDH2 on isoproterenol (ISO)-induced cardiac fibroblasts (CF) proliferation and cardiac fibrosis. It was found that ALDH2 enzymatic activity was impaired in ISO-induced HCF proliferation and Aldh2 deficiency promoted mouse CF proliferation. Alda-1, an ALDH2 activator, exerted obvious suppressive effect on ISO-induced HCF proliferation, together with the induction of cell cycle arrest at G/G phase and decreased expression of cyclin E1 and cyclin-dependent kinase 2 (CDK2). Mechanistically, the inhibitory role of Alda-1 on HCF proliferation was achieved by decreasing mitochondrial reactive oxygen species (ROS) production, which was partially reversed by rotenone, an inducer of ROS. In addition, wild-type mice treated with Alda-1 manifested with reduced fibrosis and better cardiac function after ISO pump. In summary, Alda-1 alleviates sympathetic excitation-induced cardiac fibrosis via decreasing mitochondrial ROS accumulation, highlighting ALDH2 activity as a promising drug target of cardiac fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2020.09.098DOI Listing
December 2020

Prostaglandin E1 attenuates post‑cardiac arrest myocardial dysfunction through inhibition of mitochondria‑mediated cardiomyocyte apoptosis.

Mol Med Rep 2021 02 10;23(2). Epub 2020 Dec 10.

Department of Emergency Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.

Post‑cardiac arrest myocardial dysfunction (PAMD) is a leading cause of death in patients undergoing resuscitation patients following cardiac arrest (CA). Although prostaglandin E1 (PGE1) is a clinical drug used to mitigate ischemia injury, its effect on PAMD remains unknown. In the present study, the protective effects of PGE1 on PAMD were evaluated in a rat model of CA and in a hypoxia‑reoxygenation (H/R) model. Rats were randomly assigned to CA, CA+PGE1 or sham groups. Asphyxia for 8 min followed by cardiopulmonary resuscitation were performed in the CA and CA+PGE1 groups. PGE1 was intravenously administered at the onset of return of spontaneous circulation (ROSC). PGE1 treatment significantly increased the ejection fraction and cardiac output within 4 h following ROSC and improved the survival rate, compared with the CA group. Moreover, PGE1 inactivated GSK3β, prevented mitochondrial permeability transition pore (mPTP) opening, while reducing cytochrome c and cleaved caspase‑3 expression, as well as cardiomyocyte apoptosis in the rat model. To examine the underlying mechanism, H/R H9c2 cells were treated with PGE1 at the start of reoxygenation. The changes in GSK3β activity, mPTP opening, cytochrome c and cleaved caspase‑3 expression, and apoptosis of H9c2 cells were consistent with those noted . The results indicated that PGE1 attenuated PAMD by inhibiting mitochondria‑mediated cardiomyocyte apoptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2020.11749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723157PMC
February 2021

Primary extraskeletal chondroblastic osteosarcoma of the pericardium: a case report and literature review.

Eur Heart J Case Rep 2020 Aug 15;4(4):1-7. Epub 2020 May 15.

Department of Emergency Medicine and Chest Pain Center, Qilu Hospital, Shandong University, No.107 Cultural West Road, Jinan, Shandong 250012, China.

Background: Primary extraskeletal chondroblastic osteosarcoma has very poor prognosis, especially in the elderly. The pericardium is an extremely rare site for this tumour.

Case Summary: A 67-year-old man presented with a large pericardial effusion and an intrapericardial mass. His past medical history of pulmonary tuberculosis led us to initially suspect tuberculous pericarditis. Primary extraskeletal chondroblastic osteosarcoma arising from the pericardium was diagnosed by the pathologist after surgery. The patient suffered severe intraoperative blood loss and surgical trauma. He went into shock and died a few hours after surgery.

Discussion: Extraskeletal chondroblastic osteosarcoma is a very rare tumour with a grim prognosis. Clinical manifestations frequently are not specific and can be explained by associated pathology. In this report, we describe an unusual case of primary extraskeletal chondroblastic osteosarcoma located in the pericardium and present a review of the literature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ehjcr/ytaa115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501906PMC
August 2020

Intercalated disc protein Xinβ is required for Hippo-YAP signaling in the heart.

Nat Commun 2020 09 16;11(1):4666. Epub 2020 Sep 16.

Department of Cardiology, Boston Children's Hospital, Harvard Medical School, 320 Longwood Avenue, Boston, MA, 02115, USA.

Intercalated discs (ICD), specific cell-to-cell contacts that connect adjacent cardiomyocytes, ensure mechanical and electrochemical coupling during contraction of the heart. Mutations in genes encoding ICD components are linked to cardiovascular diseases. Here, we show that loss of Xinβ, a newly-identified component of ICDs, results in cardiomyocyte proliferation defects and cardiomyopathy. We uncovered a role for Xinβ in signaling via the Hippo-YAP pathway by recruiting NF2 to the ICD to modulate cardiac function. In Xinβ mutant hearts levels of phosphorylated NF2 are substantially reduced, suggesting an impairment of Hippo-YAP signaling. Cardiac-specific overexpression of YAP rescues cardiac defects in Xinβ knock-out mice-indicating a functional and genetic interaction between Xinβ and YAP. Our study reveals a molecular mechanism by which cardiac-expressed intercalated disc protein Xinβ modulates Hippo-YAP signaling to control heart development and cardiac function in a tissue specific manner. Consequently, this pathway may represent a therapeutic target for the treatment of cardiovascular diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-18379-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494909PMC
September 2020

Visualization of human T lymphocyte-mediated eradication of cancer cells in vivo.

Proc Natl Acad Sci U S A 2020 09 28;117(37):22910-22919. Epub 2020 Aug 28.

Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, 171 65 Stockholm, Sweden;

Lymphocyte-based immunotherapy has emerged as a breakthrough in cancer therapy for both hematologic and solid malignancies. In a subpopulation of cancer patients, this powerful therapeutic modality converts malignancy to clinically manageable disease. However, the T cell- and chimeric antigen receptor T (CAR-T) cell-mediated antimetastatic activity, especially their impacts on microscopic metastatic lesions, has not yet been investigated. Here we report a living zebrafish model that allows us to visualize the metastatic cancer cell killing effect by tumor- infiltrating lymphocytes (TILs) and CAR-T cells in vivo at the single-cell level. In a freshly isolated primary human melanoma, specific TILs effectively eliminated metastatic cancer cells in the living body. This potent metastasis-eradicating effect was validated using a human lymphoma model with CAR-T cells. Furthermore, cancer-associated fibroblasts protected metastatic cancer cells from T cell-mediated killing. Our data provide an in vivo platform to validate antimetastatic effects by human T cell-mediated immunotherapy. This unique technology may serve as a precision medicine platform for assessing anticancer effects of cellular immunotherapy in vivo before administration to human cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2009092117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502706PMC
September 2020

The influence of side-chain conformations on the phase behavior of bottlebrush block polymers.

Soft Matter 2020 Sep 12;16(34):8047-8056. Epub 2020 Aug 12.

School of Chemistry & Key Laboratory of Bio-Inspired Smart Interfacial Science and Technology of Ministry of Education & Center of Soft Matter Physics and Its Applications, Beihang University, Beijing 100191, China.

A self-consistent field theory based on the wormlike chain model is implemented in the investigation of the self-assembly behavior of bottlebrush block polymers in the formation of a lamellar phase. We utilize the model in which the semi-flexible side chains of two types A and B are grafted at the semi-flexible backbone of type C to mimic the bottlebrush molecule, particularly allowing for the extended chain conformation due to the high grafting density. We examine the positional and orientational probability distribution for the segments along the backbone and side chains as a function of the grafting density and chain flexibility for all blocks, covering a broad regime spanning from the flexible chain to rigid rod chain. This reveals that the persistence length of side chains λ which intrinsically tunes the chain conformation of bottlebrush polymers plays a pivotal role in determining the manner of the local monomer packing in microphase segregation. As an important adjustable factor, λ has a remarkable impact on the backbone extension and then realizes the effective manipulation of the characteristic structural size of self-assembled microstructures, such as the domain spacing and the interfacial width.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0sm00918kDOI Listing
September 2020
-->