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1.
Food Chem ; 337: 127753, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32777566

RESUMO

The effects of treatment with melatonin on ripening of 'Fuji' apples during storage at 1 °C for 56 d were investigated. The apples were harvested at the commercial ripening stage and treated with 1 mmol L-1 melatonin. Compared with the control, melatonin treated apples had significant reduced ethylene production (28 d-56 d) and weight loss (14 d-56 d) during storage (p < 0.05). Also, the melatonin treatment maintained better apple skin structure throughout storage. The reduced ethylene production was regulated by the decreased expressions of MdACO1, MdACS1, MdAP2.4 and MdERF109, based on RNA-Seq analysis, which was validated using qRT-PCR analysis. Moreover, the activity of 3 enzymes, including peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT), were significantly increased in melatonin treated fruit (p < 0.05). Taken together, this study highlights the inhibitory effects of melatonin in ethylene biosynthesis and factors influencing postharvest quality in apple.

2.
Mol Neurobiol ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33057926

RESUMO

There is increasing evidence that EphA1 is involved in the function and development of the central nervous system, especially in neuroinflammation. It has been found to affect the disease progression of Alzheimer's disease (AD) by regulating the neuroinflammatory process. Neuroinflammation has always been regarded as the mechanism of the development of Parkinson's disease (PD) and possible therapeutic targets. Therefore, it is worth studying whether EphA1 has a potential therapeutic value for PD. The purpose of this study is to investigate the effect of EphA1 in mice and PD cell models and its mechanism.In this study, we verified the difference in expression of EphA1 and the effect and mechanism of EphA1 on neuropathological changes through Parkinson's patient samples, Parkinson's mice model, and Parkinson's model prepared from SH-SY5Y cells in vitro.EphA1 was highly expressed in the substantia nigra (SN) region of Parkinson mice and the Parkinson cell model, while the expression of tyrosine hydroxylase (TH) in the SN region of Parkinson mice was significantly reduced. After silenced EphA1 in the SH-SY5Y cell PD model, the expression levels of α-synuclein, inflammatory factors, and microglia-activated chemokine decreased. The co-immunoprecipitation experiment proved that EphA1 overexpression could promote the binding of CXCL12 and CXCR4. However, after silenced EphA1 and CXCL12 at the same time, the above effects brought by silenced EphA1 were suppressed. The same result appeared in mice with PD.EphA1 improves the inflammatory responses and neuropathological changes of the PD model in vivo and in vitro through the CXCL12/CXCR4 signaling pathway. Graphical abstract.

3.
Pharmacol Res ; : 105242, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33075491

RESUMO

Over a short span of two decades, the central role of angiogenesis in the treatment of wound healing, diverse cancers, nerve defect, vascular injury and several ophthalmic diseases has become evident. Tetrahydropalmatine, as the index component of Corydalis yanhusuo W. T. Wang, is inseparable from protecting cardiovascular system, yet its role in angiogenesis has been poorly characterized. We have demonstrated the binding potential of THP and VEGFR2 using molecular docking based on the clinical experience of traditional Chinese medicine in the pretest study. Here, we identified tetrahydropalmatine (THP) as one proangiogenic trigger via regulation of arginine biosynthesis by pharmacological assays and DESI-MSI/GC-MS based metabolomics. First, the proangiogenic effects of THP were evaluated by quail chorioallantoic membrane test in vivo and multiple models of endothelial cells in vitro. According to virtual screening, the main mechanisms of THP (2/5 of the top terms with smaller p-value) were metabolic pathways. Hence, metabolomics was applied for the main mechanisms of THP and results showed the considerable metabolite difference in arginine biosynthesis (p < 0.05) altered by THP. Finally, correlated indicators were deteced using targeted metabolomics and pharmacological assays for validation, and results suggested the efficacy of THP on citrulline to arginine flux, arginine biosynthesis, and endothelial VEGFR2 expression sequentially, leading to the promotion of angiogenesis. Overall, this manuscript identified THP as the proangiogenic trigger with the potential to develop as pharmacological agents for unmet clinical needs.

4.
Oncol Lett ; 20(5): 208, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32963614

RESUMO

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-associated morbidity and mortality worldwide. Sphingosine-1-phosphate (S1P) and S1P receptor 1 (S1PR1) have been associated with the development and progression of HCC. Angiotensin II (Ang II) and Ang II receptor type 1 (AT1R) serve key roles in the progression and metastasis of HCC. However, the association and roles of Ang II/AT1R and S1P/S1PR1 in HCC have remained elusive. Therefore, the aim of the present study was to investigate the potential association between Ang II/AT1R and S1P/S1PR1 in HCC, as well as the association of AT1R and S1PR1 protein expression levels with the progression and prognosis of HCC. The results found that the serum levels of Ang II and S1P were significantly higher in patients with HCC compared with those in healthy donors. Furthermore, mRNA and protein levels of AT1R and S1PR1 were highly expressed in human HCC tissues. In addition, a positive correlation between Ang II/S1P and AT1R/S1PR1 in HCC was noted. Upregulation of AT1R and S1PR1 was associated with the progression of HCC. Patients with high AT1R and S1PR1 protein expression levels had unfavorable outcomes with respect to overall survival and recurrence-free survival compared with patients with low AT1R and S1PR1 expression levels. The present results demonstrated an association between AT1R and S1PR1 overexpression and the progression of HCC, indicating that Ang II/AT1R and S1P/S1PR may serve as valuable prognostic biomarkers for HCC.

5.
AJR Am J Roentgenol ; 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32845712

RESUMO

Background: Sinistral portal hypertension (SPH) is caused by an obstruction of the splenic vein and is a potential cause of upper gastrointestinal bleeding. Although splenic artery embolization (SAE) and splenic vein stenting (SVS) are accepted treatment options for SPH, their outcomes have not been compared directly. Objective: This retrospective study aimed to compare the outcomes of SVS and SAE for SPH-related gastrointestinal bleeding. Methods: The data of patients with SPH treated by interventional radiology between Jan 1, 2013 and Jun 1, 2019 and with at least 6-months of clinical follow-up were retrospectively identified from the hospital electronic database. Patients were divided into the SAE group (SAE alone), SVS-SAE group (SAE immediately after SVS failure according to the same procedure as in the SAE group), and SVS group (successful treatment with SVS). The patients' baseline characteristics and follow-up data were retrieved, and their clinical outcomes were compared. Results: Thirty-seven patients with SPH were included. A total of 11, 12, and 14 patients were classified into the SAE, SVS-SAE, and SVS groups, respectively. Rebleeding (e.g., hematemesis and/or melena) was significantly less common (P = 0.013) in the SVS group (7.1%, 1/14) than in the SAE and SVS-SAE groups combined (47.8%, 11/23). Splenectomy because of rebleeding was not significantly different (P = 0.630) between the SVS group (7.1%, 1/14) and the SAE and SVS-SAE groups combined (17.4%, 4/23). No interventional procedure-related mortality was observed during follow-up in any group. Conclusion: When feasible, SVS is a safe and effective treatment for SPH-related gastrointestinal bleeding that appears to better prevent rebleeding than SAE. Clinical Impact: When feasible, SVS should be recommended over SAE for the treatment of SPH-related upper gastrointestinal bleeding.

6.
Hepatology ; 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32750152

RESUMO

Circular RNAs (circRNAs) and extracellular vesicles (EVs) are involved in various malignancies. We aimed to clarify the functions and mechanisms of dysregulated circRNAs in the cells and EVs of cholangiocarcinoma (CCA). CircRNA microarray was used to identify circRNA expression profiles in CCA tissues and bile-derived EVs. Cholangiocarcinoma-associated circular RNA 1 (circ-CCAC1) expression was measured by qRT-PCR. The clinical importance of circ-CCAC1 was analyzed by receiver operating characteristic curves, Fisher's exact test, Kaplan-Meier plots, and Cox regression model. The functions of circ-CCAC1 and exosomal circ-CCAC1 were explored in CCA cells and HUVECs, respectively. Different animal models were used to verify the in vitro results. RNA sequencing, bioinformatics, RNA immunoprecipitation, RNA pulldown, chromatin immunoprecipitation followed by sequencing, and luciferase reporter assays were used to determine the regulatory networks of circ-CCAC1 in CCA cells and HUVECs. Circ-CCAC1 levels were increased in cancerous bile-resident EVs and tissues. The diagnostic and prognostic values of circ-CCAC1 were identified in patients with CCA. For CCA cells, circ-CCAC1 increased cell progression by sponging miR-514a-5p to upregulate YY1. Meanwhile, YY1 directly bound to the promoter of CAMLG to activate its transcription. Moreover, circ-CCAC1 from CCA-derived EVs was transferred to endothelial monolayer cells, disrupting endothelial barrier integrity and inducing angiogenesis. Mechanistically, circ-CCAC1 increased cell leakiness by sequestering EZH2 in the cytoplasm, thus elevating SH3GL2 expression to reduce the levels of intercellular junction proteins. In vivo studies further showed that increased circ-CCAC1 levels in circulating EVs and cells accelerated both CCA tumorigenesis and metastasis. CONCLUSION: Circ-CCAC1 plays a vital role in CCA tumorigenesis and metastasis and may be an important biomarker/therapeutic target for CCA.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32691153

RESUMO

BACKGROUND: This study was designed to detect patients with early NSCLC with tentatively using the stem signatures associated autoantibodies (AAbs), and to evaluate its latent values in the early diagnosis and precise prognosis prediction. METHODS: The serum concentrations of selective antibodies were quantitated by enzyme-linked immunosorbent assay (ELISA), and a total of 458 cases were enrolled (training set = 401; validation set = 57). TCGA databases were used to analyze the distinct expressions and prognostic values of related genes. The optimal cut-off values were 11.60 U/ml for P53, 4.90 U/ml for MAGEA1, 3.85 U/ml for SOX2, and 7.05U/ml for PGP9.5. RESULTS: We found that the stem signatures associated antibodies of MAGEA1, PGP9.5, SOX2, and TP53 exhibited high expressions in NSCLC, negatively correlating with the overall survival (OS) (P < 0.05). In the test groups, the diagnosis sensitivity of P53, PGP9.5, SOX2, and MAGEA1 reached to 21.5%, 39.0%, 50.3%, and 35.0%, respectively, and the specificity reached to 98.7%, 99.4%, 92.2%, and 97.4%. The four candidates' panel gave a sensitivity of 71.8% with a specificity of 89%. In the validation group, the detection of the four antibodies in early diagnosis of NSCLC also exhibited high specificity and sensitivity, further consolidating their potential application. CONCLUSIONS: The detection regarding stem signatures associated antibodies could be used as effective tools in early NSCLC diagnosis, but not for localized screening of cancers, and their abnormal expression was in accordance with poorer survival.

8.
Sensors (Basel) ; 20(14)2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32650574

RESUMO

Intrusion detection is only the initial part of the security system for an industrial control system. Because of the criticality of the industrial control system, professionals still make the most important security decisions. Therefore, a simple intrusion alarm has a very limited role in the security system, and intrusion detection models based on deep learning struggle to provide more information because of the lack of explanation. This limits the application of deep learning methods to industrial control network intrusion detection. We analyzed the deep neural network (DNN) model and the interpretable classification model from the perspective of information, and clarified the correlation between the calculation process of the DNN model and the classification process. By comparing the normal samples with the abnormal samples, the abnormalities that occur during the calculation of the DNN model compared to the normal samples could be found. Based on this, a layer-wise relevance propagation method was designed to map the abnormalities in the calculation process to the abnormalities of attributes. At the same time, considering that the data set may already contain some useful information, we designed filtering rules for a kind of data set that can be obtained at a low cost, so that the calculation result is presented in a more accurate manner, which should help professionals lock and address intrusion threats more quickly.

9.
Aging (Albany NY) ; 12(11): 11116-11138, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32526702

RESUMO

Pancreatic cancer is a highly invasive malignant tumor of the digestive system with an unfavorable prognosis worldwide. This trait is thought to be largely attributed to chemoresistance. Chemotherapy is the only hope for patients with advanced pancreatic cancer. Therefore, seeking new effective chemotherapy drugs has become an urgent need. The purpose of our study was to explore whether deoxyelephantopin (DET), a sesquiterpene lactone, has a potential antitumor effect in pancreatic cancer. Additionally, the antitumor effects of DET alone or in combination with gemcitabine (GEM) and the potential mechanism of this combination were revealed. In vitro experiments showed that DET suppressed the proliferation, invasion and metastasis of pancreatic cancer cells, induced cell apoptosis via oxidative stress, and enhanced GEM sensitivity by inhibiting the NF-κB signaling pathway. Beyond that, in vivo experiments showed that DET not only inhibited pancreatic tumor growth and metastasis but also amplified the antitumor capacity of GEM, which was related to the downregulation of NF-κB and its downstream gene products. In summary, it is possible that DET could be developed as a single agent or combined with conventional chemotherapy drugs to improve the treatment of pancreatic cancer.

10.
J Hazard Mater ; 399: 123034, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32544768

RESUMO

Hepatic insulin resistance (IR) is the key event for arsenic-caused type 2 diabetes (T2D). However, the unequivocal mechanism of arsenic-induced hepatic IR remains unclear. The current study determined the role of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in arsenic-induced IR and revealed the underlying mechanism. Three-month NaAsO2 gavage led to glucose intolerance and insulin insensitivity, impaired hepatic insulin signaling. Additionally, NaAsO2 upregulated the level of oxidized mitochondrial DNA (ox-mtDNA) and mitophagy, thereby activating the NLRP3 inflammasome in SD rat liver. In vitro, we demonstrated that NaAsO2-induced IR depended upon the NLRP3 inflammasome activation. Moreover, inhibiting mitophagy mitigated the NLRP3 inflammasome activation and impaired insulin signaling induced by NaAsO2. Furthermore, mitochondrial reactive oxygen species (mtROS) scavenger alleviated the upregulated ox-mtDNA and mitophagy, thereby inhibiting the NLRP3 inflammasome activation, and improving insulin signaling. Taken together, these data demonstrated that mtROS-triggered ox-mtDNA, mitophagy, and the activation of NLRP3 inflammasome was involved in arsenic-induced hepatic IR.

11.
Int J Radiat Biol ; 96(8): 980-987, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32338561

RESUMO

Purpose: Ionizing radiation has very complex biological effects, such as inducing damage to DNA and proteins, ionizing water molecules to produce toxic free radicals, and triggering genetic and somatic effects. Understanding the biomolecular response mechanism of radiation is very important for the prevention and treatment of radiation diseases. However, function information of these radiation-associated genes is hidden in numbers of scientific papers and databases, making it difficult to understand the response mechanism of ionizing radiation.Materials and methods: We collected radiation-associated genes by literature and database mining. Literature and database mining was performed on the basis of biomedical literature from PubMed and gene expression datasets from GEO respectively.Results: We built an ionizing radiation related knowledgebase RadAtlas 1.0 (http://biokb.ncpsb.org/radatlas), which contains 598 radiation-associated genes compiled from literature mining, and 611 potential radiation-associated genes collected from gene expression datasets by differential gene expression analysis. We also provide a user-friendly web interface that offers multiple search methods.Conclusions: RadAtlas collected a large amount of information about genes, biological processes, and pathways related to ionizing radiation. It is the first attempt to provide a comprehensive catalog of radiation-associated genes with literature evidence and potential radiation-associated genes with differential expression evidence. We believe that RadAtlas would be a helpful tool to understand the response mechanism to ionizing radiation.

12.
Cell Biol Toxicol ; 36(5): 493-507, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32279126

RESUMO

A percentage of colorectal cancer (CRC) patients display low sensitivity to radiotherapy, which affects its therapeutic effect. Cancer cells DNA double-strand breaks (DSBs) repair capacity is crucial for radiosensitivity, but the roles of long noncoding RNAs (lncRNAs) in this process are largely uncharacterized. This study aims to explore whether lnc-RI regulates CRC cell growth and radiosensitivity by regulating the nonhomologous end-joining (NHEJ) repair pathway. CRC cells in which lnc-RI has been silenced showed lower cell growth and higher apoptosis rates due to increased DSBs and cell cycle arrest. We found that miR-4727-5p targets both lnc-RI and LIG4 mRNA and inhibit their expression. CRC cells showed increased radiosensitivity when lnc-RI was silenced. These results reveal novel roles for lnc-RI in both DNA damage repair and radiosensitivity regulation in CRC cells. Our study revealed that lnc-RI regulates LIG4 expression through lnc-RI/miR-4727-5p/LIG4 axis and regulates NHEJ repair efficiency to participate in DNA damage repair. The level of lnc-RI was negatively correlated with the radiosensitivity of CRC cells, indicates that lnc-RI may be a potential target for CRC therapy. We also present the first report of the function of miR-4727-5p.

13.
Food Chem ; 321: 126687, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32244138

RESUMO

The effect of food processing on the level and fate of chiral pesticide residues in apple products has rarely been investigated. In this study, we used ultra-performance convergence chromatography coupled with triple quadrupole mass spectrometry to determine the content of the novel chiral acaricide cyflumetofen. The matrix-matched calibration lines were constructed for apple slices, juice, wine and vinegar, and the determination coefficients (r2) exceeded 0.9954. Acceptable average recoveries were within 81.1% to 119.9%, and the relative standard deviations (RSDs) ranged from 0.8% to 11.0%. Processing effectiveness is represented by the processing factor (PF). The results indicated that the PFs of different procedures (washing, peeling, enzymolysis, fermentation, among others.) were generally less than 1. The reduction of cyflumetofen enantiomers during fermentation was in accordance with first-order kinetics, and stereoselective behavior was observed. This study provides reliable references for the risk assessment of cyflumetofen in the processing of apple products.


Assuntos
Malus/química , Resíduos de Praguicidas/química , Propionatos/química , Acaricidas/química , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Estereoisomerismo
14.
Sensors (Basel) ; 20(8)2020 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-32290552

RESUMO

The Industrial Internet of Things (IIoT) is of great significance to the improvement of industrial efficiency and quality, and to reduce industrial costs and resources. However, there are few openly-reported practical project applications based on the IIoT up to now. For legacy automation devices in traditional industry, it is especially challenging to realize the upgrading of industrial automation adopting the IIoT technology with less investment. Based on the practical engineering experience, this paper introduces the automation renovation of a sewage treatment plant. The legacy automation devices are upgraded by the central controller of a STM32 processor (Produced by STMicroelectronics company, located in Geneva, Switzerland), and the WeChatApplet (Developed by Tencent company, located in Shenzhen, China) is used as the extended host computer. A set of remote monitoring and control systems of sewage treatment based on the IIoT is built to realize the wide-area monitoring and control of sewage treatment. The paper describes the field hardware system, wide-area monitoring and control application program, management cloud platform and security technologies in detail. The actual operation results show that the monitoring system has the requirements of high accuracy, good real-time performance, reliable operation and low cost.

15.
Front Immunol ; 11: 176, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194541

RESUMO

Adoptive cell therapy (ACT) is a kind of immunotherapy in which T cells are genetically modified to express a chimeric antigen receptor (CAR) or T cell receptor (TCR), and ACT has made a great difference in treating multiple types of tumors. ACT is not perfect, and it can be followed by severe side effects, which hampers the application of ACT in clinical trials. One of the most promising methods to minimize side effects is to endow adoptive T cells with the ability to target neoantigens, which are specific to tumor cells. With the development of antigen screening technologies, more methods can be applied to discover neoantigens in cancer cells, such as whole-exome sequencing combined with mass spectrometry, neoantigen screening through an inventory-shared neoantigen peptide library, and neoantigen discovery via trogocytosis. In this review, we focus on the side effects of existing antigens and their solutions, illustrate the strategies of finding neoantigens in CAR-T and TCR-T therapies through methods reported by other researchers, and summarize the clinical behavior of these neoantigens.

16.
J Immunother Cancer ; 8(1)2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32221014

RESUMO

BACKGROUND: Following the extensive use of immunosuppressive drugs in the clinic, immunosuppression-associated side effects have received increasing attention. Epstein-Barr virus (EBV) reactivation and related lymphoproliferative diseases (LPD) are the lethal complications observed after allogeneic hematopoietic cell transplantation (alloHCT). While studies generally suggest an association between immunosuppressants and EBV reactivation, the effects of specific immunosuppressive drugs and which T-cell subsets mediate these correlations are unclear. Vδ2+ T cells are correlated with EBV reactivation after alloHCT. Researchers have not determined whether Vδ2+ T-cell activities are affected by immunosuppressants and thereby facilitate EBV reactivation and related LPD. METHODS: A clinical cohort study of 170 patients with hematopoietic malignancies who received haploidentical hematopoietic cell transplantation (haploHCT) was performed to investigate whether the early cessation of mycophenolate mofetil (MMF) decreases EBV reactivation and related LPD and to determine whether this change is associated with the recovery of Vδ2 + T cells after transplantation. The effects of MMF on the expansion and anti-EBV capacity of Vδ2+ T cells were detected in vitro and in an immunodeficient mouse model. RESULTS: A reduction in the course of MMF significantly improved the recovery of Vδ2+ T cells from 30 to 90 days after haploHCT (p=0.002, p=0.042 and p=0.035, respectively), accompanied by a significant decrease in EBV reactivation (from 26% to 13%, p=0.033) and EBV-LPD (from 10.6% to 2.4%, p=0.029). The day-30 Vδ2+ T level remained an independent factor for EBV reactivation in patients with different MMF durations (p=0.007). In the in-vitro experiments, MMF inhibited Vδ2+ T-cell expansion and its cytotoxicity on EBV-transformed malignant cells. Furthermore, the therapeutic and prophylactic effects of adoptively transferred human Vδ2+ T cells were attenuated by the MMF treatment in immunodeficient mice with EBV-LPD. CONCLUSIONS: These results elucidated a negative effect of immunosuppressants on the anti-EBV capacity of Vδ2+ T cells. Strategies that appropriately relieve the immunosuppression may improve anti-EBV immunity by increasing the activity of Vδ2+ T cells after alloHCT.

17.
FASEB J ; 34(3): 3743-3754, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31943384

RESUMO

Wear debris-induced osteolysis and ensuing aseptic loosening is the main cause of implant failure and revision surgery. Wear debris-induced inflammatory response plays key roles in peri-implant osteolysis. Recently, substantial of evidence suggests that hydrogen sulfide (H2 S), the third gasotransmitter, is a critical player regulating inflammation. However, the role and therapeutic potential of H2 S in wear debris-induced inflammation and osteolysis remains to be defined. In the present study, we investigated the effect of H2 S on wear debris-induced pro-inflammatory cytokines expression and osteolysis in vitro and in vivo. With a slow-releasing H2 S donor GYY4137, our study demonstrated that H2 S attenuated wear debris-induced osteolysis and osteoclastogenesis in murine calvaria resorption models. The expression of tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) that stimulated by wear particles were significantly reduced by GYY4137. Further, the level of sirtuin 1 (SIRT1), which possesses anti-inflammation property, was examined in vivo and in macrophages. And we found that wear debris decreased the expression of SIRT1. Cotreated macrophages with GYY4137 in part reversed the decline of SIRT1. More importantly, with the SIRT1 recombinant lentivirus and small interfering RNAs (siRNA) against SIRT1, our data indicated that SIRT1 mediated the inhibitory effects of GYY4137 on wear debris-induced inflammation. Collectively, these results suggested that exogenous H2 S production (via H2 S donors) may represent a potential approach for the treatment of wear particle-induced osteolysis.

18.
Medicine (Baltimore) ; 99(2): e18737, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914090

RESUMO

Portal vein thrombosis (PVT) might impair the prognosis of cirrhotic patients. However, formation of de novo PVT after transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients without preexisting PVT was rarely reported. Moreover, it is not known whether warfarin is efficient in preventing de novo PVT after TIPS. The current study aimed to investigate retrospectively the incidence and location of de novo PVT, and preventive effects of warfarin on de novo PVT after TIPS for cirrhotic patients. Patients who received TIPS placement between March 1, 2015 and March 1, 2016 in our hospital were screened retrospectively. Patients without preexisting PVT before TIPS and those who were followed up for at least 12 months were included. There were 2 groups: 1 group received warfarin (warfarin group) post-TIPS, while another group (control group) did not receive prophylactic drug to prevent PVT. Their baseline characteristics and follow-up data were retrieved. The occurrence of PVT, adverse events due to warfarin, difference in stent patency and clinical complications such as stent dysfunction, hepatic encephalopathy, mortality, liver cancer, variceal bleeding, infection, and liver failure, and results of follow-up biochemical examination were compared. Eighty-three patients without preexisting PVT were included. There were 56 patients in the control group and 27 in the warfarin group. The incidence of PVT in the warfarin group was 14.8% (4/27), whereas the incidence in the control group was 42.9% (24/56, P = .013). The location of de novo PVT was mainly at left portal vein. Adverse events due to warfarin was mostly mild, such as hemorrhinia and gingival hemorrhage. No significant difference regarding to stent patency and clinical complications between the 2 groups was found. At 24-month after-TIPS, for the remaining patients in both groups, the total bilirubin was significantly increased while the red blood cell count was significantly decreased in control group compared with those in warfarin group (P < .05). PVT could commonly occur after TIPS in patients without preexisting PVT. Warfarin could prevent PVT in these patients, and might improve patient's liver function.


Assuntos
Cirrose Hepática/cirurgia , Veia Porta/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Trombose/etiologia , Trombose/prevenção & controle , Varfarina/administração & dosagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Varfarina/efeitos adversos
19.
J Hazard Mater ; 384: 121390, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31735470

RESUMO

Chronic arsenic exposure is a significantly risk factor for pancreatic dysfunction and type 2 diabetes (T2D). Ferroptosis is a newly identified iron-dependent form of oxidative cell death that relies on lipid peroxidation. Previous data have indicated that ferroptosis is involved in various diseases, including cancers, neurodegenerative diseases, and T2D. However, the concrete effect and mechanism of ferroptosis on pancreatic dysfunction triggered by arsenic remains unknown. In this study, we verified that ferroptosis occurred in animal models of arsenic-induced pancreatic dysfunction through assessing proferroptotic markers and morphological changes in mitochondria. In vitro, arsenic caused execution of ferroptosis in a dose-dependent manner, which could be significantly reduced by ferrostatin-1. Additionally, arsenic damaged mitochondria manifested as diminishing of mitochondrial membrane potential, reduced cytochrome c level and production of mitochondrial reactive oxygen species (MtROS) in MIN6 cells. Using the Mito-TEMPO, we found the autophagy level and subsequent ferroptotic cell death induced by arsenic were both alleviated. With autophagy inhibitor chloroquine, we further revealed that ferritin regulated ferroptosis through the MtROS-autophagy pathway. Collectively, NaAsO2-induced ferroptotic cell death is relied on the MtROS-dependent autophagy by regulating the iron homeostasis. Ferroptosis is involved in pancreatic dysfunction triggered by arsenic, and arsenic-induced ferroptosis involves MtROS, autophagy, ferritin.

20.
J Cell Biochem ; 121(3): 2632-2642, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31680319

RESUMO

Circular RNAs play an imperative role in cancer development and metastasis by regulating oncogenic and tumor-suppressive pathways. However, the role and mechanism of circ_0074027 in non-small-cell lung cancer (NSCLC) have not been elucidated. The expression levels of circ_0074027 were detected by qRT-PCR. The link between circ_0074027 expression and clinicopathologic parameters was analyzed by Fisher's exact test. The prognostic role of circ_0074027 was investigated by Kaplan-Meier and Cox regression analysis. Cell counting kit-8 and flow cytometric assays were utilized to evaluate NSCLC cell proliferation and apoptosis, respectively. Wound scratch and Transwell tests were applied to detect cell migratory and invasive capacities. The interaction potential of circ_0074027 and miR-185-3p was analyzed by the circBank database, and verified by dual-luciferase reporter assay. The downstream gene of miR-185-3p was also investigated. Circ_0074027 was elevated in NSCLC specimens and cell lines. Overexpressed circ_0074027 was related to more advanced TNM stages, poorer differentiation grade, and worse overall survival. Upregulated circ_0074027 increased the proliferation of H1299 cells by inhibiting cell apoptosis. Cell migration and invasion were enhanced after circ_0074027 overexpression. Silenced circ_0074027 caused the opposite effects in the A549 cell line. For mechanism investigation, circ_0074027 directly sponges miR-185-3p to enhance bromodomain-containing protein 4 (BRD4) and MAPK-activating death domain-containing protein (MADD) expression levels at the posttranscriptional level. Furthermore, we found the oncogenic function of circ_0074027 is attributed to its modulation of BRD4 and MADD. Collectively, upregulated circ_0074027 in NSCLC accelerates cell progression via miR-185-3p/BRD4/MADD pathway as a competing endogenous RNA.

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