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1.
J Cell Physiol ; 235(1): 294-303, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31206688

RESUMO

Diabetes is a leading cause of microvascular complications, such as nephropathy and retinopathy. Recent studies have proposed that hyperglycemia-induced endothelial cell dysfunction is modulated by mitochondrial stress. Therefore, our experiment was to detect the upstream mediator of mitochondrial stress in hyperglycemia-treated endothelial cells with a focus on macrophage-stimulating 1 (Mst1) and mitochondrial fission. Our data illuminated that hyperglycemia incubation reduced cell viability, as well as increased apoptosis ratio in endothelial cell, and this alteration seemed to be associated with Mst1 upregulation. Inhibition of Mst1 via transfection of Mst1 siRNA into an endothelial cell could sustain cell viability and maintain mitochondrial function. At the molecular levels, endothelial cell death was accompanied with the activation of mitochondrial oxidative stress, mitochondrial apoptosis, and mitochondrial fission. Genetic ablation of Mst1 could reduce mitochondrial oxidative injury, block mitochondrial apoptosis, and repress mitochondrial fission. Besides, we also found Mst1 triggered mitochondrial dysfunction as well as endothelial cell damage through augmenting JNK pathway. Suppression of JNK largely ameliorated the protective actions of Mst1 silencing on hyperglycemia-treated endothelial cells and sustain mitochondrial function. The present study identifies Mst1 as a primary key mediator for hyperglycemia-induced mitochondrial damage and endothelial cell dysfunction. Increased Mst1 impairs mitochondrial function and activates endothelial cell death via opening mitochondrial death pathway through JNK.

2.
Pediatr Res ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578036

RESUMO

BACKGROUND: Cigarette smoking is associated with shorter telomere lengths in adults, but evidence on the effect of prenatal tobacco exposure is limited. We aimed to investigate the association between prenatal second-hand smoke exposure and newborn telomere length. METHODS: We recruited 762 mother-newborn pairs from Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital) between November 2013 and March 2015. Information on second-hand smoke exposure was obtained via questionnaires. Relative telomere length was measured in DNA extracted from umbilical cord blood. We used linear regression to assess the associations between prenatal second-hand smoke exposure and newborn telomere length. RESULTS: In the fully adjusted model, prenatal second-hand smoke exposure was associated with 9.7% shorter newborn telomere length (percent difference: -9.7%; 95% confidence interval (CI): -15.0, -4.0). The estimate for boys was lower (percent difference: -10.9%; 95% CI: -18.6, -2.5) than that for girls (percent difference: -8.5%; 95% CI: -15.8, -0.5), but the interaction term between newborn sex and prenatal second-hand smoke was not significant (P = 0.751). CONCLUSIONS: This study demonstrated that prenatal second-hand smoke exposure may be a preventable risk factor for accelerated biological aging in the intrauterine stage, and further suggested possible sex differences in the susceptibility to prenatal second-hand smoke.

3.
Intern Med J ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566840

RESUMO

BACKGROUND: High baseline level of soluble suppression of tumorigenicity 2 (sST2) was an independent predictor of cardiovascular death and heart failure in ST-segment elevation myocardial infarction (STEMI). AIM: To investigate the value of serum sST2 baseline levels in predicting myocardial reperfusion in patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). METHODS: Consecutive STEMI patients who underwent PPCI within 12 h after the onset of chest pain were enrolled, and were divided into TMPG 0/1/2 group and TMPG 3 group based on post-procedural Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grading (TMPG). Baseline clinical characteristics, lesions and procedural characteristics were compared. Univariate logistic regression and multivariate linear logistic analysis were performed to identify independent predictors of impaired myocardial reperfusion (TMPG 0/1/2). Receiver-operating characteristics curve (ROC) analysis of sST2 was performed to identify the optimal cutoff value for predicting the myocardial reperfusion. RESULTS: A total of 121 patients were enrolled in this study. Univariate logistic regression analysis showed that killip II-III, high levels of sST2 and BNP were risk factors of TMPG 0/1/2. Multivariable logistic regression analysis revealed that sST2 was an independent predictor of impaired myocardial reperfusion (OR 12.318, 95% CI 4.567-33.220, P < 0.001). ROC curve analysis showed that the area under curve of sST2 was 0.849, and the best cutoff value was 2.003 ng/ ml, with a sensitivity of 89.2% and a specificity of 67.9%. CONCLUSION: The elevated levels of sST2 on admission were associated with impaired myocardial reperfusion in STEMI patients undergoing PPCI. This article is protected by copyright. All rights reserved.

4.
Biomater Sci ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31602445

RESUMO

Fibrous chitin dressing (FCD) prepared from a NaOH-urea aqueous solution of chitin via a physical process was used to study its effect on wound healing using a full-thickness cutaneous wound model in rats and mice. It was demonstrated that wounds in rats covered with the FCD showed faster collagen (especially type I collagen) growth and speedier healing than those with Gauze (12 days versus 16 days). The ability of FCD to promote wound healing was also observed on wild-type (WT) mice. For MyD88-knockout mice, however, FCD displayed no beneficial but an adverse effect on wound healing: the healing time for wounds treated with FCD was even longer than those treated with gauze. Importantly, in vivo studies indicated that FCD-treated mice, compared to gauze-treated ones, exhibited markedly higher expressions of MyD88, IKBα, TGF-ß, P-TßR II, TßR II and P-Smad2/3 in wild-type mice. For MyD88 knockout mice, however, the expressions of those molecules were inhibited and lowered in FCD-treated ones than those treated with gauze. In vitro studies confirmed that chitin increased the expression of TGF-ß, P-TßRII and P-Smad2/3 while the expressions of those molecules were significantly inhibited with CD14 antibody (p < 0.05). These results indicated that FCD accelerated wound healing through a MyD88-dependent pathway, followed by a TGF-ß/Smad pathway. This work not only demonstrated the superior wound healing effect of chitin-derived dressing, but also provided for the first time the underlying molecular mechanism, further establishing chitin as an important biomedical material for potential clinical applications.

5.
J Clin Lab Anal ; : e23069, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31602678

RESUMO

OBJECTIVE: To evaluate the diagnostic accuracy of cerebrospinal fluid (CSF)-based routine clinical examinations for post-neurosurgical bacterial meningitis (PNBM) in multicenter post-neurosurgical patients. METHODS: The diagnostic accuracies of routine examinations to distinguish between PNBM and post-neurosurgical aseptic meningitis (PNAM) were evaluated by determining the values of the area under the curve (AUC) of the receiver operating characteristic curve in a retrospective analysis of post-neurosurgical patients in four centers. RESULTS: An algorithm was constructed using the logistic analysis as a classical method to maximize the capacity for differentiating the two classes by integrating the measurements of five variables. The AUC value of this algorithm was 0.907, which was significantly higher than those of individual routine blood/CSF examinations. The predicted value from 70 PNBM patients was greater than the cutoff value, and the diagnostic accuracy rate was 75.3%. The results of 181 patients with PNAM showed that 172 patients could be correctly identified with specificity of 95.3%, while the overall correctness rate of the algorithm was 88.6%. CONCLUSIONS: Routine biomarkers such as CSF/blood glucose ratio (C/B-Glu), CSF lactate (C-Lac), CSF glucose concentration (C-Glu), CSF leukocyte count (C-Leu), and blood glucose concentration (B-Glu) can be used for auxiliary diagnosis of PNBM. The multicenter retrospective research revealed that the combination of the five abovementioned biomarkers can effectively improve the efficacy of the PNBM diagnosis.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31610651

RESUMO

Cellulose was dissolved in benzyltrimethyl ammonium hydroxide (BzMe3NOH) aqueous solution, and ionic conductive cellulose hydrogels (CCHs) with antifreezing property were directly fabricated by chemical cross-linking, without further treatment. The concentrated BzMe3NOH solution in the CCH matrix endowed the hydrogel with transparency, ionic conductivity, and freeze tolerance. CCH maintained transparency over 90% and stable mechanical properties in the temperatures from -27.8 to 62.1 °C. Furthermore, the CCH-based sensors exhibited stable sensitivity to tensile strain, compressive pressure, and temperature, in a wide temperature range including the subzero temperature, with a fast responding time and no obvious hysteresis. The present work is expected to provide a simple and sustainable pathway to prepare an antifreezing soft conductor with multifunctions based on cellulose, which enables a broad range of potential applications.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31646374

RESUMO

OBJECTIVE: To investigate the presence of vimentin expression in CTCs and its clinical relevance in patients with advanced lung cancer. METHODS: Peripheral blood was obtained from 61 treatment-naive patients with advanced lung cancer. Subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) platform was applied to identify, enumerate and characterize CTCs based on cell size, aneuploidy of chromosome 8 (Chr8) and vimentin expression. Quantification and analysis of CTCs were performed on patients before chemotherapy administration and after two cycles of therapy. RESULTS: Before treatment, CTCs were detected in 60 (98.4%) patients, small cell CTCs (≤ 5 µm of WBCs) accounted for 52.8% of the absolute CTCs number, while 12 (19.7%) of the included patients had detectable vimentin-positive CTCs (vim+ CTCs). Liver metastases were reported in 7 (11.5%) patients and were significantly correlated to the presence of Vim+ CTCs (p = 0.002), with a high positivity rate of 71.4% (5/7). Vim+ CTCs were mostly in small cell size and Chr8 aneuploidy (77.0% and 82.05%, respectively). Baseline small cell CTCs ≥ 2/6 ml, triploid CTCs ≥ 2/6 ml, Vim+ CTCs ≥ 1/6 ml were found to significantly correlate with poor progression-free survival (PFS) (p = 0.017, p = 0.009 and p = 0.001, respectively). After adjusting for clinically significant factors, baseline Vim+ CTCs ≥ 1/6 ml was the only independent predictor of poor PFS [hazard ratio (HR):2.756, 95% confidence interval (CI): 1.239-6.131; p = 0.013]. CONCLUSIONS: This study demonstrates an important morphologic, karyotypic and phenotypic CTCs heterogeneity in advanced lung cancer patients. The majority of Vim+ CTCs are in small size and Chr8 aneuploidy. Baseline presence of Vim+ CTCs is correlated with liver metastases and may help predict poor PFS.

8.
Biosens Bioelectron ; 147: 111769, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31630030

RESUMO

Rapid and accurate detection of nucleic acids plays a major role in biological research and clinical diagnostics. Here, a 3D multiple self-cleaning electrochemical ratiometric microfluidic paper-based analytical device (SER-µPAD) has been constructed for manganese super oxide dismutase (MnSOD) gene detection on the basis of the inner reference probe and exonuclease Ш (Exo Ш)-assisted analytes recycling amplification method. To simplify manual operations, a multipath self-cleaning tab that could manipulate fluid transport was introduced into the paper-based device, realizing time-programmable self-cleaning of the electrode. For achieving sensitive detection of MnSOD gene, the methylene blue (MB)-modified capture probe (CP) as the inner reference element was first self-assembled on triangular Au nanosheets modified paper working electrode to provide a built-in correction and improve the detection accuracy. When MnSOD gene existed, it hybridized with the hairpin-structured signal probe, triggering the cyclic amplification with the assistance of Exo Ш selective digestion to engender numerous residual DNA labeled with ferrocene (Fc) that could be captured on electrode surface by CPs. Hence, the Fc tags were close to the electrode surface, resulting in the oxidation peak current of Fc (IFc) increase, while that of MB (IMB) was constant on account of the unchanged distance between the MB tags and the electrode. The value of IFc/IMB was linear with MnSOD gene concentration from 10 nM to 1200 nM, and the detection limit was 3.91 nM. This strategy provides an accurate, robust, and sensitive method for nucleic acids detection and shows great potential in the construction of portable devices.

9.
Biosens Bioelectron ; 147: 111786, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31654824

RESUMO

Herein, a new "on-off-on" signal switch system combined triple helix molecular switch with efficient charge separation and transfer between different sensitization units was designed for the ultrasensitive photoelectrochemical (PEC) determination of prostate-specific antigen (PSA). Concretely, the initial "signal-on" state was obtained via the cascaded sensitization structure consisting of type-II CdTe@CdSe core-shell quantum dots (QDs), CdS QDs, and ZnO nanotubes, which were assembled on Au nanoparticles modified paper fibers with the aid of signal transduction probe (STP). Thereinto, the type-II CdTe@CdSe QDs with hole-localizing core and electron-localizing shell could enable the ultrafast charge transfer and retard the charge recombination, magnifying the initial photocurrent response and preserving the high efficiency of signal-switchable PEC aptasensing system. Subsequently, the PSA aptamer (PSA-Apt) modified with gold nanoparticles (GNPs) was introduced by the hybridization of PSA-Apt with STP and the hairpin configuration of STP changed from closed to open state, forming a triple-helix structure. Hence, the CdTe@CdSe QDs labeled on the terminal of STP moved away from the electrode surface while the GNPs kept attached close to it. The proposed aptasensor turned to "signal-off" state because of the dual inhibition of vanished cosensitization effect and signal quenching effect of GNPs. Upon the target recognition, the triple-helix structure was perturbed with the formation of DNA-protein complex and the recovery of STP hairpin structure, resulting in the second "switch-on" state. Based on the target-induced photocurrent enhancement, the proposed PEC aptasensor was utilized for the determination of PSA with high sensitivity, persuasive selectivity, and excellent stability.

10.
Environ Int ; 133(Pt B): 105222, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31655275

RESUMO

BACKGROUND: Prior studies have suggested exposure to heavy metals and endocrine disrupting chemicals could disturb the homeostasis of thyroid stimulating hormone (TSH), but no epidemiology study concerning the influence of rare earth elements (REE) exposure during pregnancy on neonatal TSH levels. The present study aimed to investigate the relationships between prenatal REE exposure and neonatal TSH levels. METHODS: A total of 7367 pregnant women were recruited from Wuhan Children's Hospital between September 2012 and October 2014 in Wuhan, China. Urinary concentrations of cerium (Ce), and ytterbium (Yb) were measured by inductively coupled plasma mass spectrometry (ICP-MS). Immunofluorescence assay was used to detect neonatal TSH levels. The associations between REE exposure and neonatal TSH levels were evaluated using multivariate linear regression models. RESULTS: The geometric means of maternal urinary Ce and Yb concentrations were 0.060 µg/g creatinine and 0.025 µg/g creatinine, respectively. The results showed that per doubling of maternal urinary Ce and Yb were associated with 4.07% (95% CI: -5.80%, -2.31%), 5.13% (95% CI: -6.93%, -3.30%) decreased neonatal TSH levels respectively in the adjusted model. Sex stratified analysis demonstrated that the decreased neonatal TSH levels were observed both in male infants and female infants, and the decrease was greater in male infants in urinary Ce. There were no significant interactions between maternal urinary Ce, Yb and infant sex (Ce: P for interaction = 0.173, Yb: P for interaction = 0.967). CONCLUSIONS: Our findings demonstrated that increased maternal urinary Ce and Yb were associated with decreased neonatal TSH levels. Further researches from different populations are warranted to verify the association and to explore the mechanisms.

11.
Arch Biochem Biophys ; 676: 108137, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31605677

RESUMO

Cell fusion is a highly regulated process involved in cancer development, tissue regeneration and other physiological and pathological events. Many studies have shown that cancer cells can fuse with different types of cells such as mesenchymal stem cells (MSCs) and macrophages, which are behaved as two important fusogenic candidates in the tumor microenvironment. However, the underlying mechanisms of cell fusion between macrophages and malignant cells in cancer progression has not been fully clarified. The aim of the present study was to investigate the effects and mechanisms of cell fusion between macrophages and breast cancer cells on tumorigenesis and metastasis. Our results indicated that the hybrids exhibited enhanced proliferation, colony formation, migration and invasion capabilities, as well as suppressed apoptosis compared with parental breast cancer cells. Moreover, the hybrid cells displayed EMT with a significant downregulation of E-cadherin and upregulation of N-cadherin, Vimentin and Snail, as well as an obviously increased expression of MMP-2, MMP-9, uPA and S100A4. Mechanistically, we found that the TCF/LEF transcription factor activity of Wnt/ß-catenin pathway and the expression of its downstream target genes including cyclin D1 and c-Myc were increased in the hybrid cells. Furthermore, our data confirmed that the promoting effects of fusion of macrophages on breast cancer cell proliferation, migration and invasion could be blocked by treatment with XAV-939, a Wnt/ß-catenin signaling pathway inhibitor. In conclusion, our findings demonstrate that fusion of macrophages promotes proliferation, migration and invasion of breast cancer cells through activating EMT and Wnt/ß-catenin signaling pathway. Our current study will further contribute to elucidate the mechanism of cell fusion in tumorigenesis and metastasis, and to develop a new therapeutic strategy for breast cancer treatment.

12.
Urol J ; 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31630384

RESUMO

PURPOSE: To investigate the clinical implications of CD3+CD69+ T-cells and CD8+CD28+ T-cells in the peripheral blood of patients prior to radical prostatectomy. MATERIALS AND METHODS: A total of 91 prostate cancer (PCa) patients and 50 benign prostatic hyperplasia (BPH) patients were enrolled from January 2016 to December 2017. The proportions of CD3+CD69+ T-cells and CD8+CD28+ T-cells in the peripheral blood of PCa and BPH patients were detected by flow cytometry, and the association of these T-cell populations with pathological Grade Group and pathological TNM classification was evaluated. Data analysis was performed with SAS version 9.4 software. RESULTS: The proportions of CD3+CD69+ and CD8+CD28+ T-cells in peripheral blood were higher in PCa patients than those in BPH patients. Multivariate analysis identified a higher CD3+CD69+ T-cell proportion as a risk factor for PCa (odds ratio (OR)=4.783, P=0.0013), but the diagnostic efficacy of the CD3+CD69+ T-cell proportion (area under the curve (AUC)=0.6833, P=0.0003) for PCa was still inferior to that of the tPSA level (AUC=0.7531, P<0.0001). The AUCs for CD3+CD69+ T-cell and CD8+CD28+ T-cell proportions for PCa were 0.6959 (P=0.0372) and 0.6935 (P=0.0395), respectively, among men with tPSA levels of 4.0-10.0 ng/ml. A lower CD3+CD69+ T-cell proportion was associated with higher pathological Grade Group (P=0.0074). CONCLUSION: The proportions of CD3+CD69+ T-cells and CD8+CD28+ T-cells in peripheral blood are potential diagnostic indicators for PCa. The preoperative proportion of CD3+CD69+ T-cells in peripheral blood may have prognostic value in terms of the pathological Grade Group in PCa.

13.
Curr Hypertens Rep ; 21(11): 88, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31599364

RESUMO

PURPOSE OF REVIEW: To evaluate the status of elevated blood pressure in Chinese children and adolescents, and identify potential influence factors. RECENT FINDINGS: We searched PubMed, the Web of science, the WanFang, the VIP, and the CNKI to identify articles that were published from Jan 1, 1997, to May 30, 2019. We used random effects models to estimate the pooled prevalence of elevated blood pressure, and heterogeneity among the studies was assessed with Cochran's Q statistic. The potential source of heterogeneity was explored by meta-regression and subgroup comparisons using Q test based on ANOVA. Fifty-nine studies were included in the qualitative synthesis and the prevalence of elevated blood pressure ranged from 2.2 to 26.4%. The meta-analysis included 25 studies (341,281 participants), and the pooled prevalence of elevated blood pressure was 9.8% (95% CI 7.9, 11.9). The prevalence of elevated blood pressure in the obese children (34.1%, 95% CI 26.9, 41.7) and overweight children (15.5%, 95% CI 10.1, 21.7) was much higher than that in the normal or underweight children (5.0%, 95% CI 2.4, 8.4). Fluctuating trends in the prevalence of elevated blood pressure both in the total sample of Chinese children and adolescents and in each subgroup were observed from 2007 to 2014. Our study showed that prevalence of elevated blood pressure in children and adolescents in China was in the medium level in the world. Primary prevention for childhood hypertension should be implemented and focus on weight control and healthy lifestyle habits.

14.
Molecules ; 24(20)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640126

RESUMO

In this work, a two-phase system composed of hydrophobic ionic liquid (IL) and water phases was introduced to prepare copper sulfide (CuS) nanoparticles. It was found that CuS particles generated from the interfaces of carboxyl-functionalized IL and sodium sulfide (Na2S) aqueous solution were prone to aggregate into nanoplates and those produced from the interfaces of carboxyl-functionalized IL and thioacetamide (TAA) aqueous solution tended to aggregate into nanospheres. Both the CuS nanoplates and nanospheres exhibited a good absorption ability for ultraviolet and visible light. Furthermore, the CuS nanoplates and nanospheres showed highly efficient photocatalytic activity in degrading rhodamine B (RhB). Compared with the reported CuS nanostructures, the CuS nanoparticles prepared in this work could degrade RhB under natural sunlight irradiation. Finally, the production of CuS from the interfaces of hydrophobic IL and water phases had the advantages of mild reaction conditions and ease of operation.

15.
Atherosclerosis ; 290: 52-58, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31568962

RESUMO

BACKGROUND AND AIMS: International guidelines recommend ticagrelor over clopidogrel as preferred antiplatelet agent in patients following coronary stenting. However, no large real-life evidence is available in East Asians in general, and Chinese in particular, with regard to associated clinical outcomes. The present study aimed to assess the early and delayed outcomes after ticagrelor versus clopidogrel in post stenting Chinese patients. METHODS: We conducted the pre-specified interim analysis of Comparison Of Efficacy and Safety Between TIcagrelor and Clopidogrel In Chinese (COSTIC), the ongoing prospective, observational, single-center trial. Primary outcomes include first occurrence of myocardial infarction, stroke, vascular death and Bleeding Academic Research Consortium (BARC) scale bleeding event. Propensity score matching (PSM) was carried out to adjust for differences in baseline characteristics between treatment arms. RESULTS: In total, 4,465 patients were enrolled. After PSM, the patients prescribed with ticagrelor had a lower incidence of primary efficacy endpoint relative to those with clopidogrel (0.6% vs. 1.4%, HR = 0.44, 95%CI: 0.22-0.89, p = 0.019) at 1 month, but similar at 7 days, 6 months and 12 months. Further analysis indicated that the difference only exists in the subgroup of acute myocardial infarction (AMI) patients. With regard to safety, ticagrelor consistently increased the risk of BARC type 2 bleeding compared to clopidogrel at 1 month, 6 months and 12 months. CONCLUSIONS: These preliminary data indicate that ticagrelor is superior to clopidogrel with regard to major vascular thrombotic outcomes at 1 month, especially in the AMI population, but both groups are similar at 7 days, 6 months and 12 months. Ticagrelor consistently caused significantly more BARC type 2 bleeding.

16.
Biochem Biophys Res Commun ; 520(1): 171-178, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31582222

RESUMO

SS-31 is a kind of mitochondrion-targeted peptide. Recent studies indicated significant neuroprotective effects of SS-31. In this study, we investigated that SS-31 protected the murine cultured microglial cells (BV-2) against lipopolysaccharide (LPS)-induced inflammation and oxidative stress through stabilizing mitochondrial morphology. The morphological study showed that SS-31 preserved LPS-induced mitochondrial ultrastructure by reducing the fission protein 1 (Fis1) expression. Flow cytometry and Western blot verified that SS-31 defended the BV-2 cells against LPS-stimulated inflammation and oxidative stress via suppressing Fis1. To sum up, our study represents that SS-31 preserves BV-2 cells from LPS-stimulated inflammation and oxidative stress by down-regulating the Fis1 expression.

17.
Biosci Rep ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31661545

RESUMO

DLK1 regulates noncanonical Notch signaling pathway as ligand. DLK1 was abnormally expressed in a variety of tumors, affecting tumorigenesis and developments. The biological function of DLK1 towards cell proliferation and signaling activation was controversial across different cell types. Two currently known isoforms of DLK1, which are membrane-tethered isoform and soluble isoform, are believed to be the key of DLK1 dual behaviors. While these isoforms are not enough to explain the phenomena, our observations offer the possibility of a third isoform of DLK1. In this study, we verified the nuclear localization of DLK1 in lung cancer cells. The nuclear localized DLK1 was observed in 107 of 351 non-small cell lung cancer (NSCLC) samples and was associated with tissue differentiation and tumor size. Through co-IP combined Mass-spectrometry, we identified NCOR1 (nuclear receptor corepressor 1) as DLK1's novel interaction protein and confirmed their interaction in nuclear. We analysed the expression of NCOR1 in two independent cohort and demonstrated that NCOR1 is a tumor suppressor and has prognosis potential in lung squamous carcinomas. At last, we analyzed the colocalization of DLK1 and NCOR1 in 147 NSCLC samples by immunohistochemistry. The result indicated NCOR1 might participate with nuclear localized DLK1 in regulating cell differentiation.

18.
Mil Med Res ; 6(1): 29, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31522692

RESUMO

High-dependency units (HDUs) provide high-level care to patients who suffer from single organ failure, with the exception of respiratory failure requiring mechanical ventilation; HDUs serve as an intermediary between general wards and Intensive Care Units. Due to military and civilian needs, our hospital has established a unique HDU for patients with liver disease in China. A Chinese military officer in the United Nations Peacekeeping Forces in South Sudan was transferred to our HDU for liver failure treatment in 2018. The patient's disease status, nutrition, sleep habits, and psychological behaviour were monitored on different scales. The patient was provided with vascular monitoring, telemetry, pulse oximetry, drug treatment, nutritional support, sleep intervention, psychological intervention, and humanistic care by a multidisciplinary treatment team. After treatment, the patient recovered and avoided liver transplantation. Based on the experience with this HDU, this new model may create an efficient treatment process for military and civilian patients with severe liver disease at home or abroad.

19.
Biochem Biophys Res Commun ; 519(1): 179-185, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31493869

RESUMO

Oxidative stress plays a significant role involved in myocardial ischemia/reperfusion (MI/R) injury. The regulated in development and DNA damage response 1 (REDD1) is an mTORC1 inhibitor participating in response to hypoxia and oxidative stress. However, whether and how REDD1 is associated with MI/R injury are unclear. By investigating an in vitro model, we reveal that REDD1 is induced by HIF-1α in H9c2 cells subjected to oxygen/glucose deprivation followed by reperfusion (OGD/R). Further, cells depleted of REDD1 exhibit less OGD/R-induced injury, as evidenced by reduced lactate dehydrogenase (LDH) release and decreased apoptosis. Moreover, Nrf2 silencing abrogates REDD1 depletion-reduced reactive oxygen species (ROS) level and OGD/R-induced injury, indicating that the REDD1 depletion-mediated cellular protection is dependent on Nrf2-eliminated oxidative stress. Lastly, REDD1 depletion activates Akt/mTORC1 pathway following OGD/R treatment, and inhibition of this pathway using both LY294002 and rapamycin abrogates REDD1 effects. Altogether, these results suggest that REDD1 depletion protects H9c2 cells against OGD/R-induced injury through ameliorating oxidative stress, which is modulated by Akt/mTORC1/Nrf2 signaling. Our study may also reveal REDD1 as a potential therapeutic target for improving cardioprotection in MI/R injury treatment.

20.
Biomed Pharmacother ; 118: 109313, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545233

RESUMO

Bone marrow-derived mesenchymal stem cells (MSCs) from systemic lupus erythematosus patients (SLE-BMSCs) exhibited abnormalities in cytokine production and immune modulation. Deregulation of Nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome plays an important role in SLE. Herein, we explored whether miRNAs are involved in the regulation of NLRP3 in SLE-BMSCs. ELISA assay was used to detect the levels of inflammatory cytokines. The expression levels of let-7f-5p and gene mRNAs were determined by qRT-PCR assay. The protein levels of NLRP3, Cleaved caspase-1 and ASC were measured by western blot. The interaction between let-7f-5p and NLRP3 was verified using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. In vivo assay was performed to explore whether let-7f-5p upregulation could ameliorate inflammation in MRL/lpr mice. Our data indicated that SLE patients had significantly serum higher levels of IFN-γ, IL-6, IL-18, IL-12, IL-13 and IL-1ß. We demonstrated that NLRP3 expression was upregulated in SLE-BMSCs. Let-7f-5p directly targeted NLRP3 and repressed NLRP3 expression. NLRP3 depletion or let-7f-5p upregulation repressed IL-1ß production and the expression of NLRP3 inflammasome components. Moreover, upregulated let-7f-5p-mediated anti-inflammation effect was significantly abrogated by NLRP3 expression restoration. Besides, let-7f-5p upregulation ameliorated inflammation through modulating NLRP3 in vivo. In conclusion, our study suggested that high level of let-7f-5p alleviated inflammation in SLE-BMSCs at least partly through targeting NLRP3, highlighting let-7f-5p as a novel promising therapeutic strategy for SLE treatment.

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