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1.
Artigo em Inglês | MEDLINE | ID: mdl-32071245

RESUMO

Recurrence and metastasis remain the major obstacles to successful treatment of hepatocellular carcinoma (HCC). Chromatin remodeling factor ARID2 is commonly mutated in HCC, indicating its important role in cancer development. However, its role in HCC metastasis is largely elusive. In this study, we find that ARID2 expression is significantly decreased in metastatic HCC tissues, showing negative correlation with pathological grade, organ metastasis and positive association with survival of HCC patients. ARID2 inhibits migration and invasion of HCC cells in vitro and metastasis in vivo. Moreover, ARID2 knockout promotes pulmonary metastasis in different HCC mouse models. Mechanistic study reveals that ARID2 represses epithelial-mesenchymal transition (EMT) of HCC cells by recruiting DNMT1 to Snail promoter, which increases promoter methylation and inhibits Snail transcription. In addition, we discover that ARID2 mutants with disrupted C2H2 domain lose the metastasis suppressor function, exhibiting a positive association with HCC metastasis and poor prognosis. In conclusion, our study reveals the metastasis suppressor role as well as the underlying mechanism of ARID2 in HCC and provides a potential therapeutic target for ARID2-deficient HCC.

2.
Metabolism ; 104: 154140, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926204

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases that may progress to liver fibrosis or cancer. The present study aimed to investigate the role of microRNA-125b-5p (miR-125b-5p) in NAFLD and to further explore underlying molecular mechanisms. METHODS: A mouse model of NAFLD was constructed by high cholesterol diet feeding and a cell-model was developed by treating the mouse liver cell line NCTC1469 with palmitic acid. Gain- and loss-of-function experiments were performed to determine the effects of miR-125b-5p, integrin α8 (ITGA8), and the RhoA signaling pathway on liver fibrosis in NAFLD. After the expression levels of miR-125b-5p, ITGA8, and RhoA were determined, liver fibrosis was evaluated in vivo and in vitro. The binding relationship of miR-125b-5p and ITGA8 was then validated. Finally, miR-125b-5p promoter methylation in NAFLD liver tissues and cells was determined. RESULTS: In NAFLD clinical samples, mouse model, and cell-model, miR-125b-5p expression was reduced, while ITGA8 expression was increased. Moreover, miR-125b-5p targeted and downregulated ITGA8, leading to inhibition of the RhoA signaling pathway. In NAFLD liver tissues and cells, the CpG island in the miR-125b-5p promoter was methylated, causing epigenetic silencing of miR-125b-5p. Both miR-125b-5p silencing and ITGA8 overexpression promoted in vitro and in vivo liver fibrosis in NAFLD via activation of the RhoA signaling pathway. CONCLUSIONS: Collectively, epigenetic silencing of miR-125b-5p upregulates ITGA8 expression to activate the RhoA signaling pathway, leading to liver fibrosis in NAFLD.

3.
BMC Cancer ; 20(1): 42, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31952506

RESUMO

Following publication of the original article [1], the authors reported an error in Fig 5 of this article, graphs presenting FCM and immunofluorescent for CD4T, CD8T and NK cell of the Control Groups (LL2, LL2-irradation, MCS-irradiation) were inadvertently duplicated from another parallel experiment.

4.
Int J Obes (Lond) ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911662

RESUMO

OBJECTIVE: Ectopic lipid deposition is closely associated with type 2 diabetes (T2D). Accumulating evidence shows that GLP-1 receptor agonists (GLP-1 RAs) improve obesity and liver steatosis. However, it remains unknown whether and how they ameliorate lipid deposition in skeletal muscle. This study aimed to investigate the effect of exenatide (a GLP-1 RA) on intramyocellular lipid deposition in the skeletal muscle of T2D models and its dependence on weight loss. METHODS: Ob/ob mice and diet-induced obese (DIO) mice were treated with exenatide (24 nmol/kg), leptin (1 mg/kg), or saline control intraperitoneally once daily for 4 weeks. Phenotypic evaluations were performed during and after the intervention. PA-induced myoblast C2C12 cells were used as an in vitro model. The expression of key enzymes involved in lipid metabolism was assessed in the skeletal muscle of ob/ob mice and DIO mice. RESULTS: In ob/ob mice, 4-week exenatide treatment did not improve the body weight and fat mass, but modestly ameliorated intramyocellular lipid deposition and lipid profiles. In DIO mice, it remarkably alleviated the body weight, lipid profiles, and intramyocellular lipid deposition. In the skeletal muscle of these two models, exenatide treatment activated the AMP-activated protein kinase (AMPK) signaling pathway, stimulated lipid oxidation enzymes, and upregulated the insulin signaling pathway. In vitro, exendin-4 activated the AMPK signaling pathway and stimulated lipid metabolism to improve lipid accumulation in palmitate-induced myoblast C2C12 cells. CONCLUSIONS: Exenatide ameliorated intramyocellular lipid deposition without body weight reduction in ob/ob mice, but alleviated body weight and intramyocellular lipid deposition in DIO mice. The underlying mechanism included the activation of AMPK signaling pathway and improvement in insulin sensitivity, independent of weight loss in ob/ob mice.

5.
J Cell Mol Med ; 24(2): 1541-1552, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31793207

RESUMO

Both PNPLA3 I148M and hepatic inflammation are associated with nonalcoholic fatty liver disease (NAFLD) progression. This study aimed to elucidate whether PNPLA3 I148M is involved in NF-kB-related inflammation regulation in NAFLD. HepG2 cells homozygous for the PNPLA3 I148M mutation were used. The human PNPLA3 promoter sequence was screened for NF-kB binding sites using the MATCH and PATCH tools. NF-kB-mediated transcriptional regulation of the PNPLA3 gene was assessed by luciferase reporter assay, EMSA and ChIP-qPCR. Wild-type (I148I) and mutant (M148M) PNPLA3 were overexpressed using stable lentivirus-mediated transfection. The pCMV vector and siRNA were transiently transfected into cells to direct NF-kB overexpression and PNPLA3 silencing, respectively. A putative NF-kB binding site in the human PNPLA3 promoter was shown to be necessary for basal and NF-kB-driven transcriptional activation of PNPLA3 and protein/DNA complex formation. Supershift analysis demonstrated a protein/DNA complex specifically containing the NF-kB p65 and p50 subunits. ChIP-qPCR confirmed the endogenous binding of NF-kB to the human PNPLA3 promoter in response to NF-kB overexpression and palmitic acid (PA) challenge. The silencing of PNPLA3 blocked the overexpression of NF-kB or PA-induced TNF-α up-regulation. Moreover, mutant PNPLA3 overexpression prevented NF-kB inhibitor-induced down-regulation of TNF-α expression in PA-treated HepG2 cells. Finally, the overexpression of mutant but not wild-type PNPLA3 increased TNF-α expression and activated the ER stress-mediated and NF-kB-independent inflammatory IRE-1α/JNK/c-Jun pathway. Human PNPLA3 was shown to be a target of NF-kB, and PNPLA3 I148M mediated the regulatory effect of NF-kB on inflammation in PA-treated HepG2 cells, most likely via the IRE-1α/JNK/c-Jun ER stress pathway.

6.
Zhen Ci Yan Jiu ; 44(12): 898-905, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31867910

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) on inflammatory reaction and insulin sensitivity in insulin-resistant obese (OIR) rats. METHODS: Thirteen male Wistar rats were randomly selected as the control group and fed with common diet. The other 39 rats were fed with high-fat diet for 8 weeks to establish OIR model and then randomized into model, EA and sham EA groups. EA (2 Hz, 1 mA) was applied to unilateral "Zusanli" (ST36), "Fenglong" (ST40), "Zhongwan" (CV12) and "Guanyuan" (CV4) for 15 min, once every other day for 8 weeks, and sham EA was applied to unilateral 4 control spots about 5 mm lateral to the aforementioned 4 acupoints after shallowly inserting acupuncture needles, but without electric current output. After 8 weeks' intervention, the body weight was recorded and the glucose infusion rate (GIR) measured using hyperinsulinemic-euglycemic clamp technique. At the 6th week of intervention, glucose contents of intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tole-rance test (IPITT) were measured. The levels of serum insulin (INS) and inflammatory factors as C-reactive protein (CRP), IL-6 and TNF-α were measured by using ELISA at the end of the treatment. The expression levels of IL-6, TNF-α, monocyte chemoattractant protein-1(MCP-1), IL-10 and IL-1ß proteins and mRNAs in the abdominal adipose tissues were detected by Western blot and quantitative real time-PCR, separately. The CD68 expression (displaying infiltration of macrophages) of adipose tissue was detected using immunohistochemistry. RESULTS: After modeling, the contents of glucose of IPGTT at 30, 60 and 120 min and those of IPITT at 15, 30, 60 and 120 min, serum INS, CRP, IL-6 and TNF-α, as well as the expression levels of IL-6, TNF-α, IL-1ß and MCP-1 proteins and mRNAs and CD68 protein were significantly increased (P<0.01, P<0.05), while the levels of GIR and IL-10 protein and mRNA were obviously decreased in the model group in comparison with those of the control group (P<0.01), suggesting an increase of inflammation and a decline of INS sensitivity. Following the interventions, the increased contents of glucose of IPGTT and IPITT, serum INS, CRP, IL-6 and TNF-α, expression levels of IL-6, TNF-α, IL-1ß and MCP-1 proteins and mRNAs and CD68 protein, and the decreased levels of GIR and IL-10 protein and mRNA were evidently reversed in the EA group compared with the model group (P<0.01, P<0.05) rather than those in the sham EA group (P>0.05). CONCLUSION: EA can reduce the level of inflammation and improve insulin sensitivity in OIR rats.


Assuntos
Eletroacupuntura , Resistência à Insulina , Pontos de Acupuntura , Animais , Inflamação , Insulina , Masculino , Obesidade , Ratos , Ratos Wistar
7.
BMC Cardiovasc Disord ; 19(1): 249, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699029

RESUMO

BACKGROUND: Conventional pharmacologic therapies aim to reduce fluid overload in advanced heart failure (HF) represented by intravenous (IV) loop diuretics (LDs) have sometimes not so efficacious and been reported to have side effects such as unpredictable removal of water and sodium and electrolyte disturbance. It is not certain whether early ultrafiltration (UF) is effective than LDs in relieving edema. Given the weakness of evidence for early UF in patients with fluid overload, recommendations of UF in guidelines is considered as second-line therapy only for patients with refractory congestion, who failed to respond to LD-based strategies. METHODS: The early continuous ultrafiltration in Chinese patients with congestive heart failure (EUC-CHF) trial is an open-label, registry-based, prospective study, recruiting patients with severe acute decompensated HF who are hospitalized for HF worsening due to overt fluid overload 24 h from hospital admission. Forty patients will be enrolled to two treatment groups (n = 20 for each group). The primary outcomes are the changes of weight loss and dyspnea severity score after treatment, as well as the occurrence of clinically overt major bleeding. DISCUSSION: EUC-CHF trial was primarily designed to evaluate the efficacy and safety of early UF in patients with acute decompensated HF to reduce volume overload and improve clinical outcome. The trial aims to determine if early UF in acute HF is superior to IV LDs in clinical parameter improvement without adverse events and prevents rehospitalization up to 30 days. Also the trial is expected to establish a scoring system based on Chinese population to guide early UF treatment in appropriate patients. EUC-CHF is one of the first controlled trials tailored to determine the benefit of UF with 24 h from hospital admission. TRIAL REGISTRATION: www.chictr.org.cn, ChiCTR1800019556. Registered on 18 November 2018.

8.
Diabetes Metab Res Rev ; : e3228, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31655017

RESUMO

BACKGROUND: The aim of our study is to investigate whether preproinsulin (PPI) could trigger a proinflammatory CD4+ T cell response in Chinese patients with type 1 diabetes (T1D). METHODS: Peripheral blood mononuclear cells were stimulated by a pool of 13 PPI peptides. Additional five PPI peptides previously proved to be antigenic in other cohorts of patients with T1D were also used. PPI reactive T cell responses were measured by interferon (IFN)-γ ELISPOT assay. RESULTS: Fifty-one Chinese patients with T1D were enrolled in this study and 72.34% of them were positive for at least one islet autoantibody. The stimulation index (SI) value of IFN-γ response to PPI peptide pool or peptides with dominant epitopes was below 3 in patients when SI≥3 was used as the positive cut-off value. Two peptides (B9-23 and C19-A3) restricted to DQ8 or DR4 molecule failed to induce positive IFN-γ response in patients with high-risk HLA-DQ8 or HLA-DR4/DR9 alleles. RNA-seq analysis of PPI specific CD4+ T cell lines further showed that most of the IFN-γ associated genes remained unchanged. CONCLUSIONS: This is the first report of CD4+ T cell epitope mapping of PPI in Chinese T1D. The lack of positive IFN-γ response to PPI peptides indicates that PPI might not be the principal antigenic candidate for autoreactive CD4+ T cells in Chinese T1D. Therefore, the efficacy of PPI-based immunotherapies in attenuating proinflammatory CD4+ T cell response requires further investigation.

9.
Chem Commun (Camb) ; 55(64): 9507-9510, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31329195

RESUMO

A novel palladium-catalyzed decarbonylative annulation for the synthesis of phenanthridinones from phthalimides and arynes has been developed. This catalytic system tolerates a broad range of functional groups. Mechanistic experiments demonstrate that the Pd(ii) complex B is the key intermediate, which has been confirmed by X-ray crystallography for the first time.

10.
Int J Endocrinol ; 2019: 1567095, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31236111

RESUMO

A glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (LR) had been experimentally and clinically shown to ameliorate nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the beneficial effect of LR on NAFLD in vivo and in vitro and its underlying molecular mechanism. The effects of LR were examined on the high-fat diet-induced in vivo model in mice and in vitro model of NAFLD in human HepG2 cells. Liver tissues and HepG2 cells were procured for measuring lipid metabolism, histological examination, and western blot analysis. LR administration significantly lowered the serum lipid profile and lipid disposition in vitro and in vivo because of the altered expression of enzymes on hepatic gluconeogenesis and lipid metabolism. Moreover, LR significantly decreased Src homology region 2 domain-containing phosphatase-1 (SHP1) and then increased the expression of phosphorylated-AMP-activated protein kinase (p-AMPK). However, the overexpression of SHP1 mediated by lentivirus vector reversed LR-induced improvement in lipid deposition. Moreover, SHP1 silencing could further increase the expression of p-AMPK to ameliorate lipid metabolism and relative lipogenic gene induced by LR. In addition, abrogation of AMPK by Compound C eliminated the protective effects of LR on lipid metabolism without changing the expression of SHP1. LR markedly prevented NAFLD through adjusting lipid metabolism via SHP1/AMPK signaling pathway.

11.
J Endocrinol ; 242(2): 79-89, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31137012

RESUMO

Obesity-associated chronic inflammation in adipose tissue is partly attributed to hypoxia with insufficient microcirculation. Previous studies have shown that exenatide, a glucagon-like peptide 1 (GLP-1) receptor agonist, plays an anti-inflammatory role. Here, we investigate its effects on inflammation, hypoxia and microcirculation in white adipose tissue of diet-induced obese (DIO) mice. DIO mice were injected intraperitoneally with exenatide or normal saline for 4 weeks, while mice on chow diet were used as normal controls. The mRNA and protein levels of pro-inflammatory cytokines, hypoxia-induced genes and angiogenic factors were detected. Capillary density was measured by laser confocal microscopy and immunochemistry staining. After 4-week exenatide administration, the dramatically elevated pro-inflammatory cytokines in serum and adipose tissue and macrophage infiltration in adipose tissue of DIO mice were significantly reduced. Exenatide also ameliorated expressions of hypoxia-related genes in obese fat tissue. Protein levels of endothelial markers and pro-angiogenic factors including vascular endothelial growth factor and its receptor 2 were augmented in accordance with increased capillary density by exenatide in DIO mice. Our results indicate that inflammation and hypoxia in adipose tissue can be mitigated by GLP-1 receptor agonist potentially via improved angiogenesis and microcirculation in obesity.

12.
J Zhejiang Univ Sci B ; 20(5): 449-456, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31090270

RESUMO

Mitochondrion is a semi-autonomous organelle, important for cell energy metabolism, apoptosis, the production of reactive oxygen species (ROS), and Ca2+ homeostasis. Mitochondrial DNA (mtDNA) mutation is one of the primary factors in mitochondrial disorders. Though much progress has been made, there remain many difficulties in constructing cell models for mitochondrial diseases. This seriously restricts studies related to targeted drug discovery and the mechanism and therapy for such diseases. Here we summarize the characteristics of patient-specific immortalized lymphoblastoid cells, fibroblastoid cells, cytoplasmic hybrid (cybrid) cell lines, and induced pluripotent stem cells (iPSCs)-derived differentiation cells in the study of mitochondrial disorders, as well as offering discussion of roles and advances of these cell models, particularly in the screening of drugs.


Assuntos
DNA Mitocondrial/metabolismo , Descoberta de Drogas , Doenças Mitocondriais/metabolismo , Animais , Apoptose , Cálcio/metabolismo , Diferenciação Celular , Linhagem Celular , Citoplasma/metabolismo , Metabolismo Energético , Fibroblastos/citologia , Homeostase , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Linfócitos/citologia , Mitocôndrias/metabolismo , Mutação , Fenótipo , Espécies Reativas de Oxigênio/metabolismo
13.
Stem Cell Res Ther ; 10(1): 125, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30999928

RESUMO

Stem cell transplantation (SCT) has become a promising way to treat ischemic heart failure (IHF). We performed a large-scale meta-analysis of randomized clinical trials to investigate the efficacy and safety of SCT in IHF patients. Randomized controlled trials (RCTs) involving stem cell transplantation for the treatment of IHF were identified by searching the PubMed, EMBASE, SpringerLink, Web of Science, and Cochrane Systematic Review databases as well as from reviews and the reference lists of relevant articles. Fourteen eligible randomized controlled trials were included in this study, for a total of 669 IHF patients, of which 380 patients were treated with SCT. The weighted mean difference (WMD) was calculated for changes in the New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic volumes (LVEDV and LVESV), and Canadian Cardiovascular Society (CCS) angina grade using a fixed effects model, while relative risk (RR) was used for mortality. Compared with the control group, SCT significantly lowered the NYHA class (MD = - 0.73, 95% CI - 1.32 to - 0.14, P < 0.05), LVESV (MD = - 14.80, 95% CI - 20.88 to - 8.73, P < 0.05), and CCS grade (MD = - 0.81, 95% CI - 1.45 to - 0.17, P < 0.05). Additionally, SCT increased LVEF (MD = 6.55, 95% CI 5.93 to 7.16, P < 0.05). However, LVEDV (MD = - 0.33, 95% CI - 1.09 to 0.44, P > 0.05) and mortality (RR = 0.86, 95% CI 0.45 to 1.66, P > 0.05) did not differ between the two groups. This meta-analysis suggests that SCT may contribute to the improvement of LVEF, as well as the reduction of the NYHA class, CCS grade, and LVESV. In addition, SCT does not affect mortality.

14.
Front Psychol ; 10: 758, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31001183

RESUMO

The present study examined whether perceptions of a transgressor's trustworthiness mediates the relationship between apologies and repaired trust, and the moderating role of negative emotions within this process. Chinese undergraduate students (N = 221) completed a trust game where they invested tokens in their counterpart, and either experienced no trust violation (i.e., half of the tokens returned), a trust violation (i.e., no tokens returned), or a trust violation followed by an apology. Participant's trust behavior was measured by the number of tokens they re-invested in their counterpart in a second round of the game. Participants also completed measures to assess perceptions of the transgressor's trustworthiness and emotional state. Results revealed that participants who received an apology were more likely to trust in their counterpart, compared to those who did not receive an apology, and this relationship was mediated by perceptions of the transgressor's trustworthiness. Further, the relationship between apologies and perceptions of the transgressors trustworthiness was moderated by negative emotions; apologies only improved perceptions of trustworthiness for participants who experienced less negative emotions.

15.
Stem Cell Res Ther ; 10(1): 106, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-30898155

RESUMO

BACKGROUND: Human adipose-derived stem cells (hADSCs) are an important source of cells for regenerative medicine. Evidence of extensive interactions with the surrounding microenvironment has led researchers to focus more on hADSCs as activating agents of regenerative pathways, rather than simply replacing damaged cells. Several studies have found that functional miRNAs can be packaged into exosomes and transferred from donor cells into recipient cells, indicating that transported miRNAs may be a new class of cell-to-cell regulatory species. The aim of the present study was to evaluate whether the exosome-derived miRNAs secreted by hADSCs are capable of influencing angiogenesis, a key step in tissue regeneration. METHODS: Exosomes were purified from hADSCs followed by the characterization of their phenotype and angiogenic potential in vitro. RNA sequencing was performed to detect the miRNAs that were enriched in the hADSC-derived exosomes. A miRNA-mimic experiment was used to detect the key miRNAs in the proangiogenic activity of hADSC-derived exosomes. RESULTS: Exosomes isolated from hADSCs were characterized as round membrane vesicles with a size of approximately 100 nm and were positive for CD9 and flotillin. The exosomes were internalized by primary human umbilical vein endothelial cells (HUVECs) and stimulated HUVEC proliferation and migration. Remarkably, the exosomes promoted vessel-like formation by HUVECs in a dose-dependent manner, and their maximum activity (10 µg/mL) was comparable with that of 5% FBS. The RNA-seq bioinformatics analysis predicted 1119 gene targets of the top 30 exosomal miRNAs in Gene Ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and the pathway involved in the angiogenesis was among the top KEGG pathways. Moreover, intact miR-423-5p was further demonstrated to be transferred into HUVECs via exosomes and to exert its angiogenic function by targeting Sufu. CONCLUSIONS: Exosomal miR-423-5p mediated the proangiogenic activity of hADSCs by targeting Sufu, which may contribute to the exploitation of exosomes from hADSCs as a therapeutic tool for regenerative medicine.

16.
Sci Data ; 6: 190031, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30806636

RESUMO

Adipose-derived mesenchymal stem cells (ADSCs) show considerable promise for clinical applications in regenerative medicine. We performed a large-scale single-cell transcriptomic sequencing of 24,358 cultured human ADSCs from three donors. We provide a high-quality dataset, which would be a valuable resource for dissecting the intrapopulation heterogeneity of cultured ADSCs as well as interrogating lineage priming patterns for any interested lineages at single-cell resolution.


Assuntos
Perfilação da Expressão Gênica , Células-Tronco Mesenquimais , Diferenciação Celular/genética , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Análise de Sequência de RNA , Análise de Célula Única
17.
Pediatr Neonatol ; 60(4): 447-452, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30799148

RESUMO

BACKGROUND: As the inflammatory regulators, Resistin-like molecule ß (RELMß) and Resistin might be potential biomarkers of necrotizing enterocolitis (NEC), while thrombocytopenia is often related to the severity of NEC, clinical observation suggests that thrombocytopenia might be an early biomarker of NEC. The aim of this study was to evaluate whether RELMß, Resistin and thrombocytopenia could be biomarkers for early diagnosis of NEC in preterm infants. METHODS: From January 2016 to March 2018, twenty-nine NEC preterm infants who were diagnosed with NEC (Bell's stage ≥Ⅱ) by two independent neonatologists and twenty-nine non NEC preterm infants at neonatal intensive care unit in our hospital were enrolled in this case-control study. Preterm infants with a history of serious infections (sepsis, pneumonia), asphyxia, and congenital malformations were excluded from the study. The plasma RELMß and Resistin were evaluated by enzyme linked immunosorbent assay (ELISA) and serum platelet levels were measured directly by ordinary light microscope at the diagnosis of NEC (Bell's stage ≥Ⅱ). RESULTS: Plasma RELMß levels in NEC group were significantly higher than control group (P < 0.05). The optimal cut-off value of RELMß determined by receiver operating characteristic curve (ROC) was 378.3 ng/L. The overall estimates for sensitivity and specificity of high RELMß concentrations in the detection of neonatal NEC were 71.4% and 91.7%, respectively. No significant difference was found in plasma Resistin levels between two groups (P > 0.05). If platelet level was less than 157 × 109/L, the sensitivity and specificity were 69.34% and 82.87%, respectively. Interestingly, the combination of RELMß and thrombocytopenia increased sensitivity and specificity to 82.89% and 93.21%, respectively. CONCLUSION: The combination of RELMß and thrombocytopenia was a reliable biomarker for the early diagnosis of NEC in this study with 82.89% sensitivity and 93.21% specificity, respectively.


Assuntos
Enterocolite Necrosante/diagnóstico , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Resistina/sangue , Trombocitopenia/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Diagnóstico Precoce , Enterocolite Necrosante/sangue , Enterocolite Necrosante/complicações , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Projetos Piloto , Curva ROC , Sensibilidade e Especificidade , Trombocitopenia/complicações
18.
J Org Chem ; 84(4): 2200-2208, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30688072

RESUMO

A Pd-catalyzed ring-opening reaction of 2 H-azirines with carboxylic acids was developed. This reaction undergoes nucleophilic addition between 2,3-diaryl-2 H-azirines and carboxylic acids followed by C-N single-bond cleavage and a subsequent thermal rearrangement. This method enables the rapid construction of valuable α-amido ketone derivatives with high atomic efficiency and superb functional group tolerance.

19.
Hepatology ; 69(6): 2414-2426, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30341767

RESUMO

To investigate the effect of antidiabetic agents on nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM), 75 patients with T2DM and NAFLD under inadequate glycemic control by metformin were randomized (1:1:1) to receive add-on liraglutide, sitagliptin, or insulin glargine in this 26-week trial. The primary endpoint was the change in intrahepatic lipid (IHL) from baseline to week 26 as quantified by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF). Secondary endpoints included changes in abdominal adiposity (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT]), glycated hemoglobin, and body weight from baseline to week 26. We analysed data from intent-to-treat population. MRI-PDFF, VAT, and weight decreased significantly with liraglutide (15.4% ± 5.6% to 12.5% ± 6.4%, P < 0.001; 171.4 ± 27.8 to 150.5 ± 30.8, P = 0.003; 86.6 ± 12.9 kg to 82.9 ± 11.1 kg, P = 0.005, respectively) and sitagliptin (15.5% ± 5.6% to 11.7% ± 5.0%, P = 0.001; 153.4 ± 31.5 to 139.8 ± 27.3, P = 0.027; 88.2 ± 13.6 kg to 86.5 ± 13.2 kg, P = 0.005, respectively). No significant change in MRI-PDFF, VAT, or body weight was observed with insulin glargine. SAT decreased significantly in the liraglutide group (239.9 ± 69.0 to 211.3 ± 76.1; P = 0.020) but not in the sitagliptin and insulin glargine groups. Changes from baseline in MRI-PDFF, VAT, and body weight were significantly greater with liraglutide than insulin glargine but did not differ significantly between liraglutide and sitagliptin. Conclusion: Combined with metformin, both liraglutide and sitagliptin, but not insulin glargine, reduced body weight, IHL, and VAT in addition to improving glycemic control in patients with T2DM and NAFLD.

20.
Curr Med Sci ; 38(5): 776-784, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30341512

RESUMO

Clinically, coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) is generally used to treat patients with ischemic heart failure. However, the optimal treatment strategy remains unknown. This study examined the efficacy of the two coronary revascularization strategies for severe ischemic heart failure by using a meta-analysis. Studies comparing the efficacy of CABG and PCI were obtained from PubMed, EMBASE, Google Scholar and Cochrane Central Register of Controlled Trials (CENTRAL). The quality of each eligible article was evaluated by Newcastle-Ottawa Quality Assessment Scale (NOS), and the meta-analysis was performed using Stata version 12.0 software. Eventually, 12 studies involving 9248 patients (n=4872 in CABG group; n=4376 in PCI group) were subject to the meta-analysis for subsequent pooling calculation. The pooled hazard ratio (HR) [HR=0.83, 95% CI (0.76, 0.90), P<0.001; heterogeneity, P=0.218, I2=22.9%] of CABG compared with that of PCI revealed a statistical superiority of CABG to PCI in terms of the long-term mortality. Furthermore, CABG showed more advantages over PCI with respect to the incidence of myocardial infarction [HR=0.51, 95% CI (0.39, 0.67), P<0.001; heterogeneity, P=0.707, I2=0%] and repeat revascularization [HR=0.40, 95% CI (0.27, 0.59), P<0.001; heterogeneity, P<0.001, I2=80.1%]. It was concluded that CABG appears to be more advantageous than PCI for the treatment of ischemic heart failure in the given clinical setting.


Assuntos
Insuficiência Cardíaca/cirurgia , Infarto do Miocárdio/cirurgia , Isquemia Miocárdica/cirurgia , Revascularização Miocárdica/métodos , Ponte de Artéria Coronária , Stents Farmacológicos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Humanos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/fisiopatologia , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/fisiopatologia , Intervenção Coronária Percutânea , Modelos de Riscos Proporcionais
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