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1.
J Agric Food Chem ; 72(3): 1487-1499, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38215405

ABSTRACT

Osmotin-like proteins (OLPs) play an important role in host-plant defense. In this study, a novel multiresistant OLP (IbOLP1) was screened from sweetpotato (Ipomoea batatas) with a molecular weight of 26.3 kDa. The expression level of IbOLP1 was significantly higher in resistant cultivars than susceptible ones after inoculation with Ceratocystis fimbriata, which causes black rot disease in sweetpotato. The expression of IbOLP1 in Pichia pastoris led to the lysis of yeast cells themselves. The recombinant IbOLP1 displayed antifungal, antibacterial, and antinematode activity and stability. IbOLP1 could restrain the mycelial growth and lyse spores of C. fimbriata, distinctly reducing the incidence of black rot in sweetpotato. The IbOLP1 can trigger the apoptosis of black rot spores by elevating the intracellular levels of reactive oxygen species. Collectively, these findings suggest that IbOLP1 can be used to develop natural antimicrobial resources instead of chemical agents and generate new, disease-resistant germplasm.


Subject(s)
Ascomycota , Ipomoea batatas , Reactive Oxygen Species , Spores, Fungal , Ceratocystis , Ipomoea batatas/microbiology
2.
BMC Cancer ; 22(1): 438, 2022 Apr 21.
Article in English | MEDLINE | ID: mdl-35449036

ABSTRACT

BACKGROUND: Cancer metastasis is the main cause of mortality in cancer patients. However, the drugs targeting metastasis processes are still lacking, which is partially due to the short of effective in vitro model for cell invasion studies. The traditional 2-D culture method cannot reveal the interaction between cells and the surrounding extracellular matrix during invasion process, while the animal models usually are too complex to explain mechanisms in detail. Therefore, a precise and efficient 3-D in vitro model is highly desirable for cell invasion studies and drug screening tests. METHODS: Precise micro-fabrication techniques are developed and integrated with soft hydrogels for constructing of 3-D lung-cancer micro-environment, mimicking the pulmonary gland or alveoli as in vivo. RESULTS: A 3-D in vitro model for cancer cell culture and metastasis studies is developed with advanced micro-fabrication technique, combining microfluidic system with soft hydrogel. The constructed microfluidic platform can provide nutrition and bio-chemical factors in a continuous transportation mode and has the potential to form stable chemical gradient for cancer invasion research. Hundreds of micro-chamber arrays are constructed within the collagen gel, ensuring that all surrounding substrates for tumor cells are composed of natural collagen hydrogel, like the in vivo micro-environment. The 3-D in vitro model can also provide a fully transparent platform for the visual observation of the cell morphology, proliferation, invasion, cell-assembly, and even the protein expression by immune-fluorescent tests if needed. The lung-cancer cells A549 and normal lung epithelial cells (HPAEpiCs) have been seeded into the 3-D system. It is found out that cells can normally proliferate in the microwells for a long period. Moreover, although the cancer cells A549 and alveolar epithelial cells HPAEpiCs have the similar morphology on 2-D solid substrate, in the 3-D system the cancer cells A549 distributed sparsely as single round cells on the extracellular matrix (ECM) when they attached to the substrate, while the normal lung epithelial cells can form cell aggregates, like the structure of normal tissue. Importantly, cancer cells cultured in the 3-D in vitro model can exhibit the interaction between cells and extracellular matrix. As shown in the confocal microscope images, the A549 cells present round and isolated morphology without much invasion into ECM, while starting from around Day 5, cells changed their shape to be spindle-like, as in mesenchymal morphology, and then started to destroy the surrounding ECM and invade out of the micro-chambers. CONCLUSIONS: A 3-D in vitro model is constructed for cancer cell invasion studies, combining the microfluidic system and micro-chamber structures within hydrogel. To show the invasion process of lung cancer cells, the cell morphology, proliferation, and invasion process are all analyzed. The results confirmed that the micro-environment in the 3-D model is vital for revealing the lung cancer cell invasion as in vivo.


Subject(s)
Extracellular Matrix , Lung Neoplasms , Animals , Collagen/metabolism , Extracellular Matrix/metabolism , Humans , Hydrogels/analysis , Hydrogels/chemistry , Hydrogels/metabolism , Lung Neoplasms/metabolism , Neoplasm Invasiveness , Tumor Microenvironment
3.
Ann Thorac Surg ; 114(4): e291-e294, 2022 10.
Article in English | MEDLINE | ID: mdl-35032449

ABSTRACT

Although thoracoscopic lung segmentectomy has made significant achievements, there is little known about how to perform subsegmentectomy, which can also acquire a safe margin for curability but with more pulmonary volume reserved. This report presents the surgical procedure for subsegmental anatomic resection of left lower lobe subsegment 6b guided by the simulation of bronchovascular branching through the use of 3-dimensional computed tomographic bronchography and angiography.


Subject(s)
Imaging, Three-Dimensional , Lung Neoplasms , Bronchography/methods , Humans , Lung/surgery , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Pneumonectomy/methods , Tomography, X-Ray Computed
4.
Ann Thorac Surg ; 114(5): 1656-1663, 2022 11.
Article in English | MEDLINE | ID: mdl-34695405

ABSTRACT

BACKGROUND: Developing a nomogram to predict improvement in moderate ischemic mitral regurgitation (IMR) after coronary artery bypass grafting (CABG) is in need. METHODS: We retrospectively collected data from 112 patients with prior myocardial infarction and moderate IMR undergoing CABG between 2010 and 2018. Patients were divided into 2 groups based on IMR degree 1 year after CABG as follows: Improved Group with no or mild IMR (n = 54) and Failure Group with moderate or severe IMR (n = 58). To determine the predictors of postoperative IMR improvement, preoperative clinical and echocardiographic data were compared, and a nomogram was formulated based on all independent predictors. Discriminative ability, calibration, and clinical usefulness of the prediction model were assessed. RESULTS: Independent predictors of IMR improvement after CABG constructing the nomogram included duration between infarction and operation, posterior-inferior to left ventricular volume ratio, maximum difference of the time to reach minimum systolic volume of 16 segments, P3 leaflet tethering angle, and annular nonplanar angle. The nomogram exhibited well-fitted calibration curves and excellent discriminative ability. The area under the receiver operating characteristic curve was 0.974. Patients with a score >236 demonstrated a high probability of IMR improvement (sensitivity, 90.7%; specificity, 93.1%). Patients in the Improved Group demonstrated greater actuarial survival rates than those in the Failure Group. CONCLUSIONS: The nomogram combining 5 preoperative clinical and echocardiographic predictors provides an accurate preoperative estimation of moderate IMR improvement after surgery, with excellent discriminative ability. Based on this nomogram, patients with a higher score have predicted higher probabilities of IMR improvement.


Subject(s)
Mitral Valve Insufficiency , Myocardial Ischemia , Humans , Mitral Valve Insufficiency/diagnosis , Mitral Valve Insufficiency/surgery , Retrospective Studies , Nomograms , Treatment Outcome , Coronary Artery Bypass , Myocardial Ischemia/complications , Myocardial Ischemia/surgery
5.
Am J Transl Res ; 13(4): 2365-2378, 2021.
Article in English | MEDLINE | ID: mdl-34017395

ABSTRACT

Exosomal miRNAs are used as novel non-invasive biomarkers for detection strategies of human disease. Here, we aimed to investigate the potential clinical value of exosomal miRNAs for myocardial infarction (MI) diagnosis and treatment. Differentially expressed miRNAs were obtained from normal cardiomyocytes, MI cardiomyocytes and adjacent normal cardiomyocytes using miRNA microarray analysis. Exosomes were isolated by centrifugation and identified by transmission electron microscopy (TEM) and western blot. The expression of miR-328-3p in exosomes was then verified by qRT-PCR. Cell apoptosis was measured using flow cytometry and TUNEL analysis. The MI severity was confirmed by masson's trichrome staining and echocardiography. MiR-328-3p was significantly increased in the MI cardiomyocytes and adjacent normal cardiomyocytes. We further confirmed miR-328-3p increasing in the exosomes from MI cardiomyocytes, which can be taken into normal cardiomyocytes. Furthermore, exogenous exosomal miR-328-3p increased apoptosis of cardiomyocytes and promoted MI. Genes regulated by miR-328-3p are mainly enriched in Caspase signaling, which is an important apoptosis regulating signaling pathway. Additionally, Caspase-3 inhibitor, Z-DEVD-FMK, reversed apoptosis and MI promoting function of miR-328-3p. Exosomal miR-328-3p is a potential novel diagnostic biomarker and therapeutic target for MI, and Z-DEVD-FMK could reverse the apoptosis progression induced by miR-328-3p.

6.
J Card Surg ; 36(8): 2714-2721, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34018259

ABSTRACT

PURPOSE: Clinical treatment of gastrointestinal neoplasms in patients with severe coronary stenosis is difficult, and it remains controversial to perform staged or simultaneous surgeries. The purpose of this study was to retrospectively analyze the feasibility and indications for simultaneous gastrointestinal tumor resection and off-pump coronary artery bypass (OPCAB) graft surgery. METHODS: Data collected from a total of five patients, including three patients with gastric cancer and two patients with colorectal cancer, who underwent simultaneous radical cancer resection and OPCAB between September 2010 and October 2019, were retrospectively analyzed. Among these patients, one had an incomplete colonic obstruction. All patients had severe coronary stenosis, and one experienced acute heart failure before surgery. OPCAB was performed first, followed by the radical cancer resection. RESULTS: All five patients were discharged from hospital without perioperative death, major cardiovascular events or anastomotic leakage. The mean postoperative hospital stay was 9.4 days. One patient experienced slight gastrointestinal bleeding after surgery, which improved with conservative treatment. After a mean follow-up of 39 months, two patients with gastric cancer died from tumor metastasis at 28 months and 37 months, while the remaining three patients did not have tumor recurrence or metastasis. None of the patients experienced myocardial ischemia. CONCLUSION: It is safe and feasible to perform simultaneous OPCAB and gastrointestinal surgeries on the premise of strictly controlling the indications for patients with gastrointestinal tumors complicated with severe coronary artery stenosis.


Subject(s)
Coronary Artery Bypass, Off-Pump , Gastrointestinal Neoplasms , Feasibility Studies , Humans , Neoplasm Recurrence, Local , Postoperative Complications/epidemiology , Retrospective Studies , Treatment Outcome
7.
J Card Surg ; 36(6): 1935-1942, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33665893

ABSTRACT

OBJECTIVE: Despite substantial advances in surgical practice, the management of patients with impaired left ventricular ejection fraction (LVEF) remains challenging. Furthermore, evidence on the outcomes of off-pump coronary artery bypass (OPCAB) surgery in this population is inconsistent. We conducted the present study to compare the short- and long-term outcomes of OPCAB in patients with different ejection fractions. METHODS: This retrospective cohort study used data from the Hua-Shan Cardiac Surgery and included consecutive patients aged ≥ 18 years who underwent OPCAB procedures during 2016-2019. The patients included in the study were followed up until death or the end of data collection. Patients with different ejection fractions were matched 1:2 using propensity score matching. Factors associated with short-term outcomes were determined using logistic regression, and Kaplan-Meier survival analyses for the differences in all-cause death were generated. RESULTS: The two propensity score matched groups consisted of 40 left ventricular dysfunction (LVD) and 80 normal left ventricular function (NLVF) patients. No significant intergroup differences were observed in the postoperative outcomes for the occurrence of left heart failure (22.5% in LVD vs. 5.0% in NLVF, p = .009). Age (odds ratio = 1.11, 95% confidence interval = 1.04-1.18) but not the preoperative LVEF was shown to be a strong predictor of short-term events in logistic regression analyses. Kaplan-Meier curves displayed similar freedom from all-cause death (p = .119) or cardio-death (p = .092) between groups. CONCLUSION: The immediate postoperative outcomes and long-term outcomes were similar between the groups, indicating that OPCAB is a safe and effective choice for patients with LVD.


Subject(s)
Coronary Artery Bypass, Off-Pump , Ventricular Dysfunction, Left , Aged , Coronary Vessels , Feasibility Studies , Humans , Retrospective Studies , Risk Factors , Stroke Volume , Treatment Outcome , Ventricular Function, Left
8.
Nanomedicine (Lond) ; 16(6): 465-480, 2021 03.
Article in English | MEDLINE | ID: mdl-33599532

ABSTRACT

Aim: To construct a long circulatory and sustained releasing H2S system and explore its protective effects on myocardial ischemia and reperfusion (I/R) injury. Materials & methods: Red blood cell (RBC) membrane-coated, diallyl trisulfide (DATS)-carrying mesoporous iron oxide nanoparticles (MIONs) (RBC-DATS-MIONs) were prepared and characterized. Cytotoxicity and cellular uptake were studied in vitro, followed by in vivo assessment of safety, distribution and effect on cardiac function following I/R injury. Results: RBC-DATS-MIONs exhibited excellent biocompatibility, extended circulatory time and controlled-release of H2S in plasma and myocardium. They exhibited superior therapeutic effects on in vitro hypoxia/reoxygenation models and in vivo myocardial I/R models, which involved various mechanisms, including anti-apoptosis, anti-inflammatory and antioxidant activities. Conclusion: This work provides a new potential platform for best utilizing the protective effects of H2S by prolonging its releasing process.


Subject(s)
Myocardial Reperfusion Injury , Nanoparticles , Erythrocyte Membrane , Humans , Hydrogen Sulfide , Myocardial Reperfusion Injury/prevention & control , Myocardium
9.
J Nanobiotechnology ; 19(1): 40, 2021 Feb 06.
Article in English | MEDLINE | ID: mdl-33549092

ABSTRACT

BACKGROUND: Cardiac arrest (CA) is a leading cause of death worldwide. Even after successful cardiopulmonary resuscitation (CPR), the majorities of survivals are companied with permanent myocardial and cerebral injury. Hydrogen sulfide (H2S) has been recognized as a novel gasotransmitter exerting multiple organ protection; however, the lacks of ideal H2S donors which can controlled release H2S to targeted organs such as heart and brain limits its application. RESULTS: This work utilized mesoporous iron oxide nanoparticle (MION) as the carriers of diallyl trisulfide (DATS), with polyethylene glycol (PEG) and lactoferrin (LF) modified to MIONs to acquire the prolonged circulation time and brain-targeting effects, and a novel targeted H2S releasing system was constructed (DATS@MION-PEG-LF), which exhibited excellent biocompatibility, controlled-releasing H2S pattern, heart and brain targeting features, and the ability to be non-invasive traced by magnetic resonance imaging. DATS@MION-PEG-LF presented potent protective effects against cerebral and cardiac ischemic injury after CA in both in vitro hypoxia/reoxygenation models and in vivo CA/CPR models, which mainly involves anti-apoptosis, anti-inflammatory and anti-oxidant mechanisms. Accordingly, the cardiac and cerebral functions were obviously improved after CA/CPR, with potentially improved survival. CONCLUSIONS: The present work provides a unique platform for targeted controlled release of H2S based on MIONs, and offers a new method for combinational myocardial and cerebral protection from ischemic injury, bringing considerable benefits for CA patients.


Subject(s)
Brain Ischemia/prevention & control , Delayed-Action Preparations/chemistry , Heart Arrest/complications , Hydrogen Sulfide/administration & dosage , Myocardial Reperfusion Injury/prevention & control , Protective Agents/administration & dosage , Allyl Compounds/administration & dosage , Allyl Compounds/therapeutic use , Animals , Antioxidants/administration & dosage , Antioxidants/therapeutic use , Brain Ischemia/etiology , Cells, Cultured , Drug Delivery Systems , Hydrogen Sulfide/therapeutic use , Magnetic Iron Oxide Nanoparticles/chemistry , Male , Mice, Inbred BALB C , Myocardial Reperfusion Injury/etiology , Protective Agents/therapeutic use , Rats, Sprague-Dawley , Sulfides/administration & dosage , Sulfides/therapeutic use
10.
Biomed Res Int ; 2020: 8925420, 2020.
Article in English | MEDLINE | ID: mdl-33015184

ABSTRACT

PURPOSE: The aim of this study is to identify hub genes and miRNAs by the miRNA-mRNA interaction network in dilated cardiomyopathy (DCM) disease. METHODS: The differentially expressed miRNAs (DEMis) and mRNAs (DEMs) were selected using data of DCM patients downloaded from the GEO database (GSE112556 and GSE3585). Gene Ontology (GO) pathway analysis and transcription factor enrichment analysis were used for selecting DEMis, and the target mRNAs of DEMis were filtered by using miRDB, miRTarBase, and TargetScan. Cytoscape software was used to visualize the network between miRNAs and mRNAs and calculate the hub genes. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyze the mRNAs in the regulatory network. RESULTS: A total of 9 DEMis and 281 DEMs were selected, from which we reconstructed the miRNA-mRNA network consisting of 7 miRNAs and 51 mRNAs. The top 10 nodes, miR-144-3p, miR-363-3p, miR-9-3p, miR-21-3p, miR-144-5p, miR-338-3p, ID4 (inhibitor of DNA binding/differentiation 4), miR-770-5p, PIK3R1 (p85α regulatory subunit of phosphoinositide 3-kinase (PI3K)), and FN1 (fibronectin 1), were identified as important regulators. CONCLUSIONS: The study uncovered several important hub genes and miRNAs involved in the pathogenesis of DCM, among which, the miR-144-3p/FN1 and miR-9-3p/FN1 pathways may play an important role in myocardial fibrosis, which can help identify the etiology of DCM, and provide potential therapeutic targets.


Subject(s)
Cardiomyopathy, Dilated/genetics , Gene Regulatory Networks , MicroRNAs/genetics , Gene Expression Profiling , Gene Expression Regulation , Gene Ontology , Humans , MicroRNAs/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transcription Factors/metabolism
11.
Cell Biochem Funct ; 38(8): 1047-1055, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32519337

ABSTRACT

Myocardial infarction (MI) leads to cardiac remodelling and heart failure. Cardiomyocyte apoptosis is considered a critical pathological phenomenon accompanying MI, but the pathogenesis mechanism remains to be explored. MicroRNAs (miRs), with the identity of negative regulator of gene expression, exist as an important contributor to apoptosis. During the experiment of this study, MI mice models were successfully established and sequencing data showed that the expression of miR-23a-5p was significantly enhanced during MI progression. Further steps were taken and it showed that apoptosis of cardiac cells weakened as miR-23a-5p was downregulated and on the contrary that apoptosis strengthened with the overexpression of miR-23a-5p. To explore its working mechanisms, bioinformatics analysis was conducted by referring to multi-databases to predict the targets of miR-23a-5p. Further analysis suggested that those downstream genes enriched in several pathways, especially in the PI3K/Akt singling pathway. Furthermore, it demonstrated that miR-23a-5p was negatively related to the phosphorylation of PI3K/Akt, which plays a critical role in triggering cell apoptosis during MI. Recilisib-activated PI3K/Akt singling pathway could restrain apoptosis from inducing miR-23a-5p overexpression, and Miltefosine-blocked PI3K/Akt singling pathway could restrict apoptosis from inhibiting miR-23a-5p reduction. In conclusion, these findings revealed the pivotal role of miR-23a-5p-PI3K/Akt axis in regulating apoptosis during MI, introducing this novel axis as a potential indicator to detect ischemic heart disease and it could be used for therapeutic intervention.


Subject(s)
Apoptosis , Down-Regulation , MicroRNAs/biosynthesis , Myocardial Infarction/metabolism , Myocytes, Cardiac/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Animals , Mice , MicroRNAs/genetics , Myocardial Infarction/genetics , Myocardial Infarction/pathology , Myocytes, Cardiac/pathology , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics
12.
Angew Chem Int Ed Engl ; 58(43): 15541-15547, 2019 Oct 21.
Article in English | MEDLINE | ID: mdl-31502747

ABSTRACT

We demonstrate a simple and effective chemical equilibrium regulation strategy to improve the efficiency of electrochemical ammonia synthesis by constructing electrochemical reaction system that works at significantly lower pressure than the Haber-Bosch process. Transferring the nitrogen reduction reaction from ambient conditions to a lightly pressurized environment not only accelerates the activation of the N≡N triple bond but also inhibits the competing reaction of hydrogen evolution while promoting the dissolution and diffusion of nitrogen. The verification experiment of using well-designed Fe3 Mo3 C/C composite nanosheets as the nitrogen reduction catalyst shows that the lower pressure reaction system can improve the Faradaic current efficiency by one order of magnitude. Moreover, the comparatively low-pressure reaction system can greatly reduce the cell voltage of the ammonia synthesis reaction (up to 33 %) even at the relatively low pressure of 0.7 MPa, which is of significance for decreasing the energy consumption of electrochemical ammonia synthesis under mild conditions.

13.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(4): 468-473, 2019 Apr.
Article in Chinese | MEDLINE | ID: mdl-31109423

ABSTRACT

OBJECTIVE: To evaluate the effect and mechanism of rivaroxaban, an inhibitor of coagulation factor Xa (FXa), on endotoxin-induced injury to human umbilical vein endothelial cells (HUVEC). METHODS: When cultured HUVEC grow to 80% fusion, they were divided into four groups according to the random number method: blank control group (DMEM medium), lipopolysaccharide (LPS) group (cells were challenged by 100 µg/L LPS for 16 hours), FXa+LPS group (cells were challenged by LPS for 16 hours after they were cultured with 100 nmol/L FXa for 24 hours), and FXa +RIV+LPS group (cells were challenged by LPS for 16 hours after they were cultured with 100 nmol/L FXa and 1 µmol/L rivaroxaban for 24 hours). After each group of cells were challenged with LPS, the cell activity was detected by the cell proliferation and toxicity kit (CCK-8); the cell migration ability was detected by cell scratch experiments; the abilities of cells migration were measured by scratch-wound-healing assay; the apoptosis of cells were evaluated using flow cytometry; the endothelial barrier of cells was assessed by Transwell and Evans blue; the levels of tumor necrosis factor-α (TNF-α), interleukin (IL-1ß, IL-6) were detected by the enzyme linked immunosorbent assay (ELISA); the expressions of nuclear factor-ΚB (NF-ΚB) and mitogen activated protein kinase (MAPK) signaling pathway were detected by Western Blot. RESULTS: Compared with blank control group, the cell viability in LPS group was significantly decreased, and the migration ability, number of apoptotic cells, and barrier permeability of endothelial cells was significantly increased, the levels of TNF-α, IL-1ß and IL-6 were significantly increased, and the expressions of phosphorylation of c-Jun N-terminal kinase (p-JNK), phosphorylation of p38MAPK (p-p38MAPK), phosphorylation of transforming growth factor kinase 1 (p-TAK1) and phosphorylation of NF-ΚBp65 (p-NF-ΚBp65) were significantly increased. It indicated that LPS could stimulate the inflammatory response of vascular endothelial cells, and had a significant impact on cell activity, apoptosis and function. There was no significant difference in above indexes between FXa+LPS group and LPS group, except for the level of IL-6 being higher in FXa+LPS group. Compared with FXa+LPS group, in FXa+RIV+LPS group, the cell activity was significantly increased (A value: 0.42±0.02 vs. 0.33±0.02), and migration ability was significantly decreased (folds: 1.78±0.17 vs. 2.24±0.20), the number of apoptotic cells was significantly decreased [(11.30±0.70)% vs. (21.03±0.19)%], and permeability of monolayers endothelial cells was significantly decreased [(149±12)% vs. (253±15)%], the levels of inflammatory cytokines were significantly decreased [IL-1ß (ng/L): 163.2±20.7 vs. 477.8±20.2, IL-6 (ng/L): 69.3±0.5 vs. 238.0±24.1, TNF-α (ng/L): 117.0±13.1 vs. 196.2±4.5], the expressions of p-TAK1 and p-NF-ΚBp65 were significantly decreased (p-TAK1/TAK1: 0.74±0.09 vs. 1.85±0.15, p-NF-ΚBp65/NF-ΚBp65: 1.15±0.17 vs. 2.36±0.20), with statistically significant differences (all P < 0.05). There was no significant difference in the p-JNK, p-p38MAPK expressions between FXa+RIV+LPS group and FXa+LPS group (p-JNK/JNK: 1.64±0.12 vs. 1.65±0.15, p-p38MAPK/p38MAPK: 2.31±0.32 vs. 2.35±0.20, both P > 0.05). CONCLUSIONS: Rivaroxaban can effectively relieve the inflammatory response of HUVEC stimulated by LPS, which may be related to the inhibition of NF-ΚB signaling pathway activation rather than MAPK signaling pathway.


Subject(s)
Endotoxins/adverse effects , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/pathology , Rivaroxaban/pharmacology , Humans , Lipopolysaccharides/metabolism , NF-kappa B/metabolism , Signal Transduction , Tumor Necrosis Factor-alpha/metabolism
14.
Nitric Oxide ; 81: 1-10, 2018 12 01.
Article in English | MEDLINE | ID: mdl-30217578

ABSTRACT

Cardiac transplantation has been limited by the inability to long preserve donor hearts safely. Hydrogen sulfide (H2S) has been recognized as an important gasotransmitter exerting potent cardioprotection from ischemia/reperfusion injury (I/R). Herein we investigated the cardioprotective effects of a novel long-term and slow-releasing H2S system, namely DATS-MSN, in heart preservation solution using a heart transplantation models. The release of H2S from DATS-MSN was slow and continuous in the University of Wisconsin solution (UW), correspondingly, DATS-MSN application demonstrated superior cardioprotective effects over the control and traditional H2S donors after 6 h heart preservation and 1 h reperfusion, associated with greater allograft performance including left ventricular developed pressure (LVDP) and dP/dt max, reduced plasmic CK-MB and troponin I levels, inhibited myocardial inflammation, increased antioxidant enzyme activities, preserved mitochondria structure and function, and decreased cardiomyocyte apoptosis index. Also, DATS-MSN application presented significant superiority in long-term allografts survival and function after 8 weeks of transplantation. In the in vitro experiments, cardiomyocytes injury from hypoxia was found to be relived with the treatment of DATS-MSN by anti-inflammatory effects via TLR4/NLRP3 pathway. The present work provides a long-term releasing H2S donor compatibly applied in the donor heart preservation, and preliminary explores its underlying mechanisms.


Subject(s)
Cardiotonic Agents/pharmacology , Heart/physiology , Hydrogen Sulfide/pharmacology , Organ Preservation/methods , Adenosine/pharmacology , Allopurinol/pharmacology , Allyl Compounds/chemistry , Animals , Apoptosis , Glutathione/pharmacology , Heart/drug effects , Heart Transplantation , Hydrogen Sulfide/chemistry , Hydrogen Sulfide/metabolism , Insulin/pharmacology , Male , Morpholines/chemistry , Morpholines/pharmacology , Myocardial Reperfusion Injury/prevention & control , Myocarditis/prevention & control , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Organ Preservation Solutions/pharmacology , Organothiophosphorus Compounds/chemistry , Organothiophosphorus Compounds/pharmacology , Oxidative Stress/drug effects , Raffinose/pharmacology , Rats, Sprague-Dawley , Sulfides/chemistry , Tissue Donors
15.
Heart Surg Forum ; 21(3): E190-E193, 2018 05 24.
Article in English | MEDLINE | ID: mdl-29893679

ABSTRACT

BACKGROUND: Constrictive pericarditis (CP) is defined as impaired diastolic cardiac function caused by a calcified and thickened pericardium. We assessed the clinical characteristics and time to diagnosis, as well as patient prognosis after pericardiectomy. Methods: We analyzed the records of 36 CP patients who underwent pericardiectomy at Huashan Hospital, China, between 2012 and 2015. Clinical manifestations, length of time to diagnosis, laboratory parameters, and diagnostic imaging results were examined. All patients underwent pericardiectomy, and were assessed post-operatively for quality of life and improvement of cardiac function using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Results: All patients displayed shortness of breath and polyserous effusion, as well as elevated pro B-type natriuretic peptide and thickened pericardium. Mean time between onset of symptoms and a definitive diagnosis of CP was 9.5 ± 2.1 months. Pericardiectomy was performed within one week of diagnosis. Mean central venous pressure decreased from a pre-operative 19.92 ± 6.6 mmHg to a post-operative 8.5 ± 2.7 mmHg. Within 1.5 ± 0.7 years of surgery, all patients maintained good quality of life and cardiac function, which resulted in a mean score of 0.9 ± 0.6 on the MLHFQ. Conclusion: A definitive diagnosis of CP is usually made long after the onset of symptoms. Early detection and diagnosis by echocardiography with elevated central venous pressure and early treatment by surgery are key to an improved prognosis and resumption of good cardiac function.


Subject(s)
Central Venous Pressure/physiology , Echocardiography/methods , Pericardiectomy/methods , Pericarditis, Constrictive/diagnosis , Pericardium/diagnostic imaging , Tomography, X-Ray Computed/methods , Adult , Female , Humans , Male , Pericarditis, Constrictive/physiopathology , Pericarditis, Constrictive/surgery , Pericardium/surgery , Prognosis , Reproducibility of Results , Retrospective Studies
16.
Eur J Cardiothorac Surg ; 54(1): 84-90, 2018 07 01.
Article in English | MEDLINE | ID: mdl-29444321

ABSTRACT

OBJECTIVES: The aim of this study was to explore the predictors of the improvement in moderate ischaemic mitral regurgitation (IMR) after off-pump coronary artery bypass grafting (OPCAB) focusing on left ventricular (LV) dyssynchrony. METHODS: A prospective study was performed among 135 patients (age at surgery, mean ± SD: 67.0 ± 8.2 years, 33.3% women) with prior myocardial infarction and moderate IMR undergoing OPCAB from 2008 to 2015. Preoperative and follow-up clinical and echocardiographic parameters were analysed, focusing on LV global/regional dyssynchrony. Patients were grouped by IMR at 1 year postoperatively: improved group with no or mild IMR (n = 61) and failure group with moderate or severe IMR (n = 67). Data were compared between groups to explore the predictors of IMR improvement after OPCAB. RESULTS: Seven patients who died before the 1-year postoperative assessment were excluded. At the 1-year follow up, there were 61 patients in the improved group and 67 patients in the failure group. Preoperatively, the improved group had smaller LV global dyssynchrony, LV regional dyssynchrony (papillary muscle systolic dyssynchrony; improved group versus failure group: 48.5 ± 4.5 ms vs 57.1 ± 3.9 ms; P < 0.001) and greater LV ejection fraction (improved group versus failure group: 44.7 ± 5.0% vs 36.7 ± 6.7%; P < 0.001) than the failure group. Papillary muscle systolic dyssynchrony (odds ratio 1.556, 95% confidence interval 1.313-1.845; P < 0.001) and preoperative ejection fraction (odds ratio 0.799, 95% confidence interval 0.691-0.924; P = 0.002) were independent predictors of moderate IMR improvement after OPCAB. CONCLUSIONS: In the selected patients, preoperative moderate IMR could be relieved by coronary artery bypass grafting. Greater ejection fraction and absence of LV regional dyssynchrony may predict the improvement in moderate IMR after coronary artery bypass grafting, suggesting that LV dyssynchrony especially regional dyssynchrony and preserved ventricular function would be important to the outcome of patients with moderate IMR.


Subject(s)
Coronary Artery Bypass, Off-Pump , Coronary Artery Disease/surgery , Mitral Valve Insufficiency/surgery , Ventricular Dysfunction, Left/complications , Aged , Coronary Artery Disease/physiopathology , Female , Humans , Male , Middle Aged , Mitral Valve Insufficiency/physiopathology , Prognosis , Prospective Studies , Stroke Volume/physiology , Treatment Outcome , Ventricular Dysfunction, Left/physiopathology , Ventricular Function, Left/physiology
17.
Zhongguo Fei Ai Za Zhi ; 19(7): 418-24, 2016 Jul 20.
Article in Chinese | MEDLINE | ID: mdl-27339718

ABSTRACT

BACKGROUND: It is so far not clear that how myasthenia gravis (MG) affected the prognosis of thymoma patients. The aim of this assay is to compare the postoperative survival between patients with thymoma only and those with both thymoma and MG. METHODS: The Chinese Alliance for Research in Thymomas (ChART) registry recruited patients with thymoma from 18 centers over the country on an intention to treat basis from 1992 to 2012. Two groups were formed according to whether the patient complicated MG. Demographic and clinical data were reviewed, Patients were followed and their survival status were analyzed. RESULTS: There were 1,850 patients included in this study, including 421 with and 1,429 without MG. Complete thymectomy were done in 91.2% patients in MG group and 71.0% in non-MG group (P<0.05). There were more percentage of patients with the histology of thymoma AB, B1, or B2 (P<0.05) in MG group, and more percentage of patients with MG were in Masaoka stage I and II. The 5 year and 10 year OS rates were both higher in MG group (93% vs 88%; 83% vs 81%, P=0.034) respectively. The survival rate was significantly higher in patients with MG when the Masaoka staging was III/IV (P=0.003). Among patients with advanced stage thymoma (stage III, IVa, IVb), the constituent ratios of III, IVa, IVb were similar between MG and Non-MG group. Histologically, however, there were significantly more proportion of AB/B1/B2/B3 in the MG group while there were more C in the non-MG group (P=0.000). Univariate analyses for all patients showed that MG, WHO classification, Masaoka stage, surgical approach, chemotherapy and radiotherapy and resectability were significant factors, and multivariate analysis showed WHO Classification, Masaoka stage, and resectability were strong independent prognostic indicators. CONCLUSIONS: Although MG is not an independent prognostic factor, the survival of patients with thymoma was superior when MG was present, especially in late Masaoka stage patients. Possible reasons included early diagnosis of the tumor, better histologic types, an overall higher R0 resection and less recurrence.
.


Subject(s)
Myasthenia Gravis/mortality , Thymoma/mortality , Thymus Neoplasms/mortality , Adult , Aged , China , Databases, Factual , Humans , Male , Middle Aged , Myasthenia Gravis/complications , Myasthenia Gravis/pathology , Myasthenia Gravis/surgery , Neoplasm Staging , Postoperative Period , Prognosis , Retrospective Studies , Survival Rate , Thymoma/complications , Thymoma/pathology , Thymoma/surgery , Thymus Neoplasms/complications , Thymus Neoplasms/pathology , Thymus Neoplasms/surgery
18.
J Thorac Dis ; 8(4): 711-7, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27114839

ABSTRACT

BACKGROUND: It is so far not clear that how myasthenia gravis (MG) affected the prognosis of thymoma patients. The aim of this assay is to compare the postoperative survival between patients with thymoma only and those with both thymoma and MG. METHODS: The Chinese Alliance for Research in Thymomas (ChART) registry recruited patients with thymoma from 18 centers over the country on an intention to treat basis from 1992 to 2012. Two groups were formed according to whether the patient complicated MG. Demographic and clinical data were reviewed, patients were followed and their survival status were analyzed. RESULTS: There were 1,850 patients included in this study, including 421 with and 1,429 without MG. Complete thymectomy were done in 91.2% patients in MG group and 71.0% in non-MG group (P<0.05). There were more percentage of patients with the histology of thymoma AB, B1, or B2 (P<0.05) in MG group, and more percentage of patients with MG were in Masaoka stage I and II. The 5- and 10-year overall survival (OS) rates were both higher in MG group (93% vs. 88%; 83% vs. 81%, P=0.034) respectively. The survival rate was significantly higher in patients with MG when the Masaoka staging was 3/4 (P=0.003). Among patients with advanced stage thymoma (stage 3, 4a, 4b), the constituent ratios of 3, 4a, 4b were similar between MG and non-MG group. Histologically, however, there were significantly more proportion of AB/B1/B2/B3 in the MG group while there were more C in the non-MG group (P=0.000). Univariate analyses for all patients showed that MG, WHO classification, Masaoka stage, surgical approach, chemotherapy and radiotherapy and resectability were significant factors, and multivariate analysis showed WHO classification, Masaoka stage, and resectability were strong independent prognostic indicators. CONCLUSIONS: Although MG is not an independent prognostic factor, the survival of patients with thymoma was superior when MG was present, especially in late Masaoka stage patients. Possible reasons included early diagnosis of the tumor, better histologic types, an overall higher R0 resection and less recurrence.

19.
PLoS One ; 9(8): e106184, 2014.
Article in English | MEDLINE | ID: mdl-25171217

ABSTRACT

Hepatic ischemia/reperfusion (I/R) injury is an unavoidable consequence of major liver surgery, especially in liver transplantation with bowel congestion, during which endotoxemia is often evident. The inflammatory response aggravated by endotoxin after I/R contributes to liver dysfunction and failure. The purpose of the present study was to investigate the protective effect of butyrate, a naturally occurring four-carbon fatty acid in the body and a dietary component of foods such as cheese and butter, on hepatic injury complicated by enterogenous endotoxin, as well as to examine the underlying mechanisms involved. SD rats were subjected to a total hepatic ischemia for 30 min after pretreatment with either vehicle or butyrate, followed by 6 h and 24 h of reperfusion. Butyrate preconditioning markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathological changes. The inflammatory factors levels, macrophages activation, TLR4 expression, and neutrophil infiltration in live were attenuated by butyrate. Butyrate also maintained the intestinal barrier structures, reversed the aberrant expression of ZO-1, and decreased the endotoxin translocation. We conclude that butyrate inhibition of endotoxin translocation, macrophages activation, inflammatory factors production, and neutrophil infiltration is involved in the alleviation of total hepatic I/R liver injury in rats. This suggests that butyrate should potentially be utilized in liver transplantation.


Subject(s)
Butyrates/therapeutic use , Constipation/complications , Liver Diseases/complications , Liver Diseases/prevention & control , Protective Agents/therapeutic use , Reperfusion Injury/complications , Reperfusion Injury/prevention & control , Animals , Anti-Inflammatory Agents/therapeutic use , Constipation/immunology , Constipation/pathology , Constipation/prevention & control , Cytokines/immunology , Endotoxins/immunology , Intestinal Mucosa/drug effects , Intestinal Mucosa/immunology , Intestinal Mucosa/pathology , Liver/drug effects , Liver/immunology , Liver/pathology , Liver Diseases/immunology , Liver Diseases/pathology , Male , Neutrophil Infiltration/drug effects , Rats , Rats, Sprague-Dawley , Reperfusion Injury/immunology , Reperfusion Injury/pathology
20.
J Surg Res ; 187(2): 653-9, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24445056

ABSTRACT

BACKGROUND: The inflammatory response after hepatic ischemia reperfusion (I/R) contributes to liver dysfunction and failure after transplantation. Butyrate is a four-carbon fatty acid, normally produced by bacterial fermentation of fiber in mammalian intestines, with anti-inflammatory activities. The purpose of the present study was to investigate the protective effect of butyrate preconditioning, if any, against hepatic I/R injury in rats and the underlying mechanisms involved. METHODS: Male Sprague-Dawley rats were subjected to a partial (70%) hepatic ischemia for 60 min after pretreatment with either vehicle or butyrate, followed by 3, 6, and 24 h of reperfusion. Hepatic injury was evaluated by biochemical and histopathologic examinations. Neutrophil infiltration was measured by myeloperoxidase (MPO) activity. The expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay (Elisa) and Real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The expression of nuclear factor kappa B (NF-κB) p65 was determined by immunohistochemistry and Western blot analysis. RESULTS: Butyrate treatment markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathologic changes. The expression of tumor necrosis factor-alpha, interleukin-6, and myeloperoxidase activity was attenuated by butyrate. Butyrate also reduced I/R-induced nuclear translocation of NF-κB p65 in Kupffer cells. CONCLUSION: Our results suggest that butyrate alleviates I/R-induced liver injury, possibly by suppressing inflammatory factors production and preventing NF-κB activation in Kupffer cells.


Subject(s)
Butyrates/pharmacology , Hepatitis/drug therapy , Kupffer Cells/drug effects , Reperfusion Injury/drug therapy , Transcription Factor RelA/antagonists & inhibitors , Transplantation Conditioning/methods , Animals , Cell Nucleus/metabolism , Hepatitis/immunology , Hepatitis/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Kupffer Cells/metabolism , Liver/drug effects , Liver/immunology , Liver/metabolism , Liver Transplantation , Male , Neutrophils/immunology , Peroxidase/metabolism , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Reperfusion Injury/immunology , Reperfusion Injury/metabolism , Transcription Factor RelA/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
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