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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 328-332, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33812395

RESUMO

OBJECTIVE: To explore the regulation effect of myeloid leukemia No.1 Chinese herb medicine prescription combined with chemotherapy on Th17 cells in bone marrow fluid of AML patients, so as to provide guidance for improving AML treatment effect and patients' long-term survival. METHODS: Seventy patients with AML who were hospitalized in Department of Hematology, Wuwei People's Hospital from April 2017 to August 2019 were selected and enrolled in AML group, 25 healthy volunteers were selected and enrolled in control group; then according to therapeutic regimen, AML patients were divided into 2 groups: combined therapy group (myeloid leukemia NO.1 Chinese herb medicine prescription combined with chemotherapy) and non-combined therapy group (chemotherapy alone). Flow cytometry was used to detect the ratio of CD3+ CD161+ IL-17+ IFN-γ+ T cells in bone marrow fluid, and ELISA was used to detect the vascular endothelial growth factor (VEGF) and interleukin-17 (IL-17) concentrations in bone marrow fluid. Statistical analysis was performed on the data with SPSS 22.0. RESULTS: The ratio of CD3+ CD161+ IL-17+ IFN-γ+ T cells, VEGF and IL-17 concentration in newly diagnosed and relapsed AML patients were significantly higher than those in the normal control group (P<0.001); while those in CR and DFS stage patients were significantly lower than those in newly diagnosed and relapsed patients (P<0.001), and the ratio of CD3+ CD161+ IL-17+ IFN-γ+ T cells, VEGF and IL-17 concentration in DFS patients with AML were not significantly different from those in the control group (P>0.05). The ratio of CD3+ CD161+ IL-17+ IFN-γ+ T cells, VEGF and IL-17 concentration in CR stage of AML patients treated with chemotherapy alone were significantly higher than those in the control group (P<0.05), but there was no difference between combined therapy group and the control group; the ratio of CD3+ CD161+ IL-17+ IFN-γ+ T cells, the concentration of VEGF and IL-17 in CR stage of AML patients treated with chemotherapy alone were higher than those of patients treated with combined therapy regimen (P<0.05). AML patients treated with combined therapy regimen had a significantly higher complete remission rate compared with patients received chemotherapy alone (P<0.05), but the recurrence rate was significantly lower (P<0.05). CONCLUSION: Th17 cells expression in bone marrow of newly diagnoses and relapsed AML patients significantly increase, and decrease significantly after treatment. Myeloid leukemia No.1 Chinese herb prescription combined with chemotherapy can significantly increase the CR rate and reduce the RL rate for AML.


Assuntos
Leucemia Mieloide Aguda , Medicina , Medula Óssea , China , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Prescrições , Células Th17 , Fator A de Crescimento do Endotélio Vascular
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 428-432, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33812410

RESUMO

OBJECTIVE: To detect the level of vascular endothelial growth factor (VEGF) in bone marrow of patients with non-M3 acute leukemia (AL), and estimate its relationship with prognosis. METHODS: From January 2016 to December 2019, 114 patients with AL in department of Hematology, Wuwei People's Hospital were selected as study group, and 25 healthy volunteers were enrolled as control group. The concentration of VEGF in bone marrow was detected by ELISA. The patients were divided into high and low concentration group according to the level of VEGF. The overall survival (OS) and event-free survival (EFS) were compared among different groups. RESULTS: The level of VEGF in patients with AL was significantly higher than that in the control group. The median OS and EFS in the low concentration group was 34.5 and 32 months, respectively, while, in the high concentration group was 30 and 26 months, respectively. The differences between the two groups were statistically significant (P=0.010). There were significant differences in OS rate (P=0.035) and EFS rate (P=0.026) between low and high concentration group. Multivariate analysis showed that high VEGF concentration was an independent risk factor affecting OS (HR=2.619, 95%CI 1.070-6.406, P=0.035) and EFS (HR=2.221, 95%CI 1.074-4.552, P=0.031) in AL patients. CONCLUSION: VEGF highly expresses in the bone marrow of patients with AL at initial diagnosis and relapse, and shows adverse effects on the prognosis.


Assuntos
Leucemia Mieloide Aguda , Fator A de Crescimento do Endotélio Vascular , Medula Óssea , Intervalo Livre de Doença , Humanos , Prognóstico
3.
Biomed Res Int ; 2021: 8835891, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763487

RESUMO

Background: Pregabalin has received wide clinical attention as a new type of analgesic. We undertake a systematic review and meta-analysis to evaluate the effect of pregabalin on postoperative pain in patients undergoing cardiac surgery. Methods: We searched PubMed, Embase, and Cochrane Library (from inception to July 2020) for eligible studies. The primary outcomes were the total morphine consumption at 24 h. A secondary outcome was intraoperative fentanyl consumption, extubation time postoperative, and length of stay in hospital. We calculated pooled weighted mean difference (WMD) or odds ratio (OR) and 95% CIs using random- or fixed-effects models. Results: Seven trials involving 463 patients were listed. Meta-analysis showed that the total morphine consumption at 24 h in the pregabalin group was significantly less than the control group (WMD: -5.44, 95% CI: -10.42-0.46, P = 0.03). We found that there is no significant difference between the two groups in intraoperative fentanyl consumption. Compared with the control group, the length of stay in hospital in the pregabalin group was significantly shorter (WMD = -0.87, 95% CI: -1.42-0.32, P = 0.002). And we found that there were no significant differences between the two groups in extubation time (WMD: 17.24, 95% CI: -24.36-58.84, P = 0.42). Conclusions: Oral pregabalin for cardiac surgery patients can effectively reduce the patient's 24-hour morphine consumption after surgery, shorten the patient's hospital stay, and is more conducive to early postoperative recovery.

4.
BMC Urol ; 21(1): 49, 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33775245

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the best-characterized and most pervasive renal cancers. The present study aimed to explore the effects and potential mechanisms of let-7i-5p in ccRCC cells. METHODS: Using bioinformatics analyses, we investigated the expression of let-7i-5p in The Cancer Genome Atlas (TCGA) database and predicted biological functions and possible target genes of let-7i-5p in ccRCC cells. Cell proliferation assay, wound healing assay and transwell invasion assay were conducted to characterize the effects of let-7i-5p in ccRCC cells. To verify the interactions between let-7i-5p and HABP4, dual-luciferase reporter assay, quantitative real-time polymerase chain reaction, and western blotting were conducted. Rescue experiments were used to investigate the relationship between let-7i-5p and HABP4. RESULTS: TCGA data analysis revealed that ccRCC tissues had significantly increased let-7i-5p expression, which was robustly associated with poor overall survival. Further verification showed that ccRCC cell proliferation, migration and invasion were inhibited by let-7i-5p inhibitor but enhanced by let-7i-5p mimics. Subsequently, HABP4 was predicted to be the target gene of let-7i-5p. TCGA data showed that ccRCC tissues had decreased expression of HABP4 and that HABP4 expression was negatively correlated with let-7i-5p. Further verification showed that downregulation of HABP4 expression promoted cell proliferation, migration and invasion. The dual-luciferase reporter gene assay suggested that the let-7i-5p/HABP4 axis was responsible for the development of ccRCC. CONCLUSION: Our results provide evidence that let-7i-5p functions as a tumor promoter in ccRCC and facilitates cell proliferation, migration and invasion by targeting HABP4. These results clarify the pathogenesis of ccRCC and offer a potential target for its treatment.

5.
Food Chem ; 350: 129276, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33609937

RESUMO

Benzo[a]pyrene (BaP), a prototype of polycyclic aromatic hydrocarbons (PAHs) with potential mutagenicity, toxicity and carcinogenicity, is ubiquitous in deep-fried foods. Herein, the changes in eight specific PAHs (PAH8) concentration in sunflower oil during frying were investigated by gas chromatography-triple quadrupole-mass spectrometry (GC-QqQ-MS). PAH8 concentrations in sunflower oil were 23.92-27.82 µg kg-1 and increased with increasing frying time. The detected BaP levels were 3.64-4.00 µg kg-1, exceeding the upper limit (2 µg kg-1) set by European Union (EU), though below the limiting value (10 µg kg-1) in China. The interaction between BaP and calf thymus DNA (ctDNA) was explored through various spectroscopic methods and molecular docking. Melting studies, denaturation experiments, ionic strength effects and viscosity measurements indicated that BaP interacted with ctDNA primarily via groove binding as evidenced by circular dichroism analysis and molecular docking. Further gel electrophoresis assays suggested that DNA was damaged at high levels of BaP.


Assuntos
Benzo(a)pireno/análise , Benzo(a)pireno/química , Culinária , DNA/química , Conformação de Ácido Nucleico , Animais , Simulação de Acoplamento Molecular
6.
Mikrochim Acta ; 188(3): 63, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33537897

RESUMO

A photothermal immunoassay using a thermometer as readout based on polyaniline@Au organic-inorganic nanohybrids was built. Temperature output is acquired due to the photothermal effect of the photothermal nanomaterial. Polyaniline@Au organic-inorganic nanohybrids were synthesized by interfacial reactions with high photothermal conversion efficiency. A sandwich structure of the immunocomplex was prepared on a microplate for determination of carcinoembryonic antigen (CEA) by polyaniline@Au organic-inorganic nanohybrids as nanolabel. The released heat based on light-to-heat conversion from the photothermal nanolabel under NIR irradiation is detectable using the thermometer. The increased temperature is directly proportional to CEA concentration. The linear range of the photothermal immunoassay is 0.20 to 25 ng mL-1 with determination limit of 0.17 ng mL-1. Polyaniline@Au organic-inorganic nanohybrids with high photothermal conversion efficiency was synthesized as labels to construct photothermal immunosensor. The sandwich-type immunoassay was built on 96 hole plate based on specific binding of antigen and antibody. Carcinoembryonic antigen in sample was detected quantitatively by thermometer readout.

9.
Eur Radiol ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33210204

RESUMO

The original version of this article, published on 24 September 2020, unfortunately contained a mistake.

10.
Infect Dis Ther ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146854

RESUMO

INTRODUCTION: Sepsis is a complication in acute-on-chronic liver failure (ACLF) patients associated with high rates of mortality and morbidity. Early diagnosis of sepsis in ACLF patients can improve prognosis. This study aimed to explore potential effective biomarkers for the early diagnosis of sepsis in ACLF patients. METHODS: Ninety-four ACLF patients with sepsis were enrolled from 10 hospitals across China from January 2015 to June 2016 as well as 49 ACLF patients without infection from Xiangya Hospital. The first-day admission data and SOFA score and CLIF-SOFA score were collected. The differences of indicators between groups were compared with Kruskal-Wallis test. The receiver-operating characteristic (ROC) curve was analyzed to evaluate the diagnostic efficiency of the selected factors. RESULTS: Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) and presepsin were significantly higher in ACLF-sepsis patients compared with ACLF patients with no infection (P < 0.001). sTREM-1 and presepsin presented higher diagnostic value in sepsis for ACLF patients compared with other biomarkers [white blood cells (WBC), procalcitonin (PCT) and C-reactive protein (CRP)]. Combining sTREM-1 or presepsin with the CLIF-SOFA score increased the diagnostic efficiency (AUC = 0.876 or AUC = 0.913, respectively). CONCLUSIONS: sTREM-1 and presepsin are potential biomarkers for the early diagnosis of sepsis in ACLF patients. The combination of presepsin and the CLIF-SOFA score is a promising method for diagnosing sepsis in ACLF patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02457637.

11.
New Phytol ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33006771

RESUMO

Post-translational modification of proteins mediated by SIZ1, a small ubiquitin-like modifier (SUMO) E3 ligase, regulates multiple biological processes in plants. However, its role in the regulation of lateral root formation remains unclear. Here, we demonstrate that the apple SUMO E3 ligase MdSIZ1 promotes lateral root formation. Using a yeast-two-hybrid (Y2H) system, the auxin response factor MdARF8 was screened out as a protein-protein interaction partner of the SUMO-conjugating E2 enzyme MdSCE1, indicating that MdARF8 may be a substrate for MdSIZ1. The interaction between MdARF8 and MdSCE1 was confirmed by pull-down, Y2H and Co-immunoprecipitation assays. MdSIZ1 enhanced the conjugating enzyme activity of MdSCE1 to form a MdSCE1-MdSIZ1-MdARF8 complex, thereby facilitating SUMO modification. We identified two arginine substitution mutations at K342 and K380 in MdARF8 that blocked MdSIZ1-mediated SUMOylation, indicating that K342 and K380 are the principal SUMOylation sites of the MdARF8 protein. Moreover, MdARF8 promoted lateral root formation in transgenic apple plants, and the phenotype of reduced lateral roots in the Arabidopsis siz1-2 mutant was restored in siz1-2/MdARF8 complementary plants. Our findings reveal an important role for sumoylation in the regulation of lateral root formation in plants.

12.
J Int Med Res ; 48(10): 300060520956473, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33044099

RESUMO

OBJECTIVE: To establish a mouse model of bioluminescent Klebsiella pneumoniae-induced lung infection, under different infection states after pretreatment with various dosages of cyclophosphamide (CTX). METHODS: A K. pneumoniae strain carrying the luxCDABE operon was used to infect immunocompetent mice (intraperitoneal injection of saline at 4 days and 1 day prior to experimental lung infection) and immunodeficient mice (50 mg/kg CTX at 4 days and 50 mg/kg CTX at 1 day prior to lung infection; or 150 mg/kg CTX at 4 days and 100 mg/kg CTX at 1 day prior to lung infection). Disease progression was monitored in living mice using a bioluminescence imaging system. The bioluminescent images, bacterial loads in lungs, blood cytological changes and histopathology of lungs were analysed. RESULTS: K. pneumoniae-induced lung infection models were established in mice pretreated with CTX. Different doses of CTX led to different severities of lung infection. Mice pretreated with 150/100 mg/kg CTX were more suitable for real-time monitoring as they had more typical bioluminescent images of lung infection, more obvious changes in the bioluminescent intensity values, more bacterial colonies in the lungs and more distinct pulmonary pathological changes. CONCLUSIONS: A stable bioluminescent K. pneumonia-induced lung infection model was successfully established in mice pretreated with CTX, which can be semi-quantitatively monitored in real-time.

13.
BMC Pregnancy Childbirth ; 20(1): 601, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028240

RESUMO

BACKGROUND: Acute fatty liver of pregnancy (AFLP) is a potentially lethal condition of pregnant women with a high mortality rate. Potential predictors related to postpartum recovery time and prognostic factors of AFLP are still unclear. This study aimed to evaluate potential predictors for prognosis and postpartum recovery time of AFLP. METHODS: We retrospectively analyzed the clinical data of 76 AFLP patients in our hospital from 2002 to 2017 and investigated potential predictors using univariate analysis and multivariate logistic regression analysis. RESULTS: Hepatic encephalopathy (HE) was found to be associated with prognosis in AFLP patients (P = 0.005, OR = 26.844). The postpartum recovery time analysis showed that AFLP patients with a age < 25 had the shortest recovery time, but no significant difference (P = 0.134, OR = 5.952). The postpartum recovery time of patients with liver failure (LF) was significantly prolonged compared to those without LF (P = 0.036, OR = 10.052). Cryoprecipitate, and plasma infusion showed no significant effect on prognosis or recovery time. Artificial liver support therapy (ALST) had no effect on prognosis, but it might affect postpartum recovery time with no statistical significance (P = 0.128, OR = 5.470). CONCLUSION: HE is a potential predictor for prognosis of AFLP. LF is a potential predictor for postpartum recovery time.

14.
Neuron ; 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33080229

RESUMO

Optogenetics has revolutionized neuroscience in small laboratory animals, but its effect on animal models more closely related to humans, such as non-human primates (NHPs), has been mixed. To make evidence-based decisions in primate optogenetics, the scientific community would benefit from a centralized database listing all attempts, successful and unsuccessful, of using optogenetics in the primate brain. We contacted members of the community to ask for their contributions to an open science initiative. As of this writing, 45 laboratories around the world contributed more than 1,000 injection experiments, including precise details regarding their methods and outcomes. Of those entries, more than half had not been published. The resource is free for everyone to consult and contribute to on the Open Science Framework website. Here we review some of the insights from this initial release of the database and discuss methodological considerations to improve the success of optogenetic experiments in NHPs.

15.
Acta Pharmacol Sin ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32939034

RESUMO

Acute liver failure (ALF) is a fatal clinical syndrome with no special drug. Recent evidence shows that modulation of macrophage to inhibit inflammation may be a promising strategy for ALF treatment. In this study we investigated the potential therapeutic effects of melittin, a major peptide component of bee venom both in mice model of ALF and in LPS-stimulated macrophages in vitro, and elucidated the underlying mechanisms. ALF was induced in mice by intraperitoneal injection of D-galactosamine/LPS. Then the mice were treated with melittin (2, 4, and 8 mg/kg, ip). We showed that melittin treatment markedly improved mortality, attenuated severe symptoms and signs, and alleviated hepatic inflammation in D-galactosamine/LPS-induced ALF mice with the optimal dose being 4 mg/kg. In addition, melittin within the effective doses did not cause significant in vivo toxicity. In LPS-stimulated RAW264.7 macrophages, melittin (0.7 µM) exerted anti-oxidation and anti-inflammation effects. We showed that LPS stimulation promoted aerobic glycolysis of macrophages through increasing glycolytic rate, upregulated the levels of Warburg effect-related enzymes and metabolites including lactate, LDHA, LDH, and GLUT-1, and activated Akt/mTOR/PKM2/HIF-1α signaling. Melittin treatment suppressed M2 isoform of pyruvate kinase (PKM2), thus disrupted the Warburg effect to alleviate inflammation. Molecular docking analysis confirmed that melittin targeted PKM2. In LPS-stimulated RAW264.7 macrophages, knockdown of PKM2 caused similar anti-inflammation effects as melittin did. In D-galactosamine/LPS-induced ALF mice, melittin treatment markedly decreased the expression levels of PKM2 and HIF-1α in liver. This work demonstrates that melittin inhibits macrophage activation-mediated inflammation via inhibition of aerobic glycolysis by targeting PKM2, which highlights a novel strategy of using melittin for ALF treatment.

16.
Eur Radiol ; 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32974686

RESUMO

OBJECTIVES: To systematically review studies on the diagnostic accuracy of spleen stiffness measurement (SSM) for the detection of clinical significant portal hypertension (CSPH), severe portal hypertension (SPH), esophageal varices (EV), and high-risk esophageal varices (HREV) in patients with chronic liver diseases (CLD). METHODS: Through a systematic search, we identified 32 studies reporting the accuracy of SSM for the diagnosis of portal hypertension (PH) and/or EV in adults with CLD. A bivariate random-effects model was performed to estimate pooled sensitivity, specificity, likelihood ratio, positive predictive value (PPV), negative predictive value (NPV), and diagnostic odds ratios (DOR). The clinical utility of SSM was evaluated by Fagan plot. RESULTS: A total of 32 studies assessing 3952 patients were included in this meta-analysis. The pooled sensitivities of SSM were 0.85 (95% confidence interval (CI), 0.69-0.93) for CSPH; 0.84 (95% CI, 0.75-0.90) for SPH; 0.90 (95% CI, 0.83-0.94) for any EV; and 0.87 (95% CI, 0.77-0.93) for HREV. The pooled specificities of SSM were 0.86 (95% CI, 0.74-0.93) for CSPH; 0.84 (95% CI, 0.72-0.91) for SPH; 0.73 (95% CI, 0.66-0.79) for EV; and 0.66 (95% CI, 0.53-0.77) for HREV. Summary PPV and NPV of SSM for detecting HREV were 0.54 (95% CI, 0.47-0.62) and 0.88 (95% CI, 0.81-0.95), respectively. CONCLUSIONS: Our meta-analysis suggests that SSM could be used as a helpful surveillance tool in management of CLD patients and was quite useful for ruling out the presence of HREV thereby avoiding unnecessary endoscopy. KEY POINTS: • SSM could be used to rule out the presence of HREV in patients with CLD thereby avoiding unnecessary endoscopy. • SSM has significant diagnostic value for CSPH and SPH with high sensitivity and specificity in patients with CLD. • SSM could be used as a helpful surveillance tool for clinicians managing CLD patients.

17.
Transfus Apher Sci ; : 102930, 2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-32933846

RESUMO

Liver-targeted cargo delivery possesses great potential for the treatment of liver disease. It is urgent to find an efficient and biocompatible liver targeted delivery system. This study focused on the liver targeting properties of erythrocyte ghosts and its possible mechanism. Herein, we optimized conditions to fabricate human and mouse erythrocyte ghosts with sufficient room capable of incorporating various model substances. Erythrocyte ghosts are biocompatible cargo carriers because it is derived from autologous red blood cells (RBCs), and the cell size, zeta potential, and biconcave-disk shape of the ghosts were consistent with those of RBCs. An in vivo imaging system and positron emission tomography/computed tomography imaging showed that the ghosts were captured mainly in the liver by intravenous injection of fluorescence or 18F-fluorodeoxyglucose (FDG)-labelled ghosts into mice. In contrast, the main concentration of naked octreotide was trapped in the lungs while naked 18F-FDG was trapped in the heart. However, the concentration of cargo-loaded ghosts decreased significantly in the liver in macrophage-depleted mice. Accordingly, in vitro experiments showed that higher phosphatidylserine exposure was observed in the ghosts (38.9 %) compared to normal erythrocytes (0.69 %), and the phagocytic activity of the macrophage RAW 264.7. on the ghosts was significantly higher than that of normal erythrocytes (p < 0.001). Together they indicate that erythrocyte ghosts show liver targeting properties, and possibly owing to macrophage phagocytosis. This promising and effective therapeutic delivery system may provide therapeutic benefits for liver disease.

18.
Chin Med J (Engl) ; 133(20): 2456-2465, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32947361

RESUMO

Immunotherapy has become the mainstay for lung cancer treatment, providing sustained therapeutic responses and improved prognosis compared with those obtained with surgery, chemotherapy, radiotherapy, and targeted therapy. It has the potential for anti-tumor treatment and killing tumor cells by activating human immunity and has moved the targets of anti-cancer therapy from malignant tumor cells to immune cell subsets. Two kinds of immune checkpoints, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1), are the main targets of current immunotherapy in lung cancer. Despite the successful outcomes achieved by immune checkpoint inhibitors, a small portion of lung cancer patients remain unresponsive to checkpoint immunotherapy or may ultimately become resistant to these agents as a result of the complex immune modulatory network in the tumor microenvironment. Therefore, it is imperative to exploit novel immunotherapy targets to further expand the proportion of patients benefiting from immunotherapy. This review summarizes the molecular features, biological function, and clinical significance of several novel checkpoints that have important roles in lung cancer immune responses beyond the CTLA-4 and PD-1/PD-L1 axes, including the markers of co-inhibitory and co-stimulatory T lymphocyte pathways and inhibitory markers of macrophages and natural killer cells.

19.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(8): 897-902, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32800039

RESUMO

A female infant, aged 43 days, had shortness of breath, cyanosis, groan, and dyspnea since birth. Physical examination showed cyanosis of lips and three-concave sign, and multiple lung imaging examinations showed diffuse ground-glass opacities in both lungs. The girl was given anti-infective therapy and continuous mechanical ventilation but there were no significant improvements in symptoms. Gene testing confirmed a compound heterozygous mutation, c.1890C>A(p.Tyr630Ter)+c.3208G>A(p.Ala1070Thr), in the ABCA3 gene, with the former from her father and the latter from her mother. Pathological examination of the lungs indicated pulmonary interstitial disease. The girl was diagnosed with infantile diffuse pulmonary interstitial disease caused by mutations in the ABCA3 gene. When full-term neonates experience shortness of breath and dyspnea after birth, pulmonary imaging suggests diffuse ground-glass changes, and conventional treatment is not effective (ventilator-dependent), congenital pulmonary surfactant metabolism defects needs to be considered. Gene testing, which can provide a basis for early intervention, prognostic evaluation, and genetic counseling, should be performed as early as possible.


Assuntos
Dispneia , Feminino , Humanos , Lactente , Pulmão , Doenças Pulmonares Intersticiais , Mutação , Surfactantes Pulmonares
20.
Cell Signal ; 75: 109738, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32818670

RESUMO

PURPOSE: Our study aimed to study the role of lncRNA TP73-AS1/miR-539/MMP-8 axis in modulating M2 macrophage polarization in hepatocellular carcinoma (HCC). METHODS: The gene expression levels of TP73-AS1, miR-539 and MMP-8 were modified by transfection with the overexpression or knockdown vectors. The patient survival rate was analyzed using Kaplan-Meier method. The levels of TP73-AS1, miR-539, MMP-8 and M1/2 macrophage polarization markers were analyzed by qRT-PCR, western blot, and flow cytometry. The release of TGF-ß1 in the supernatant was determined by ELISA assay. The interaction between TP73-AS1, miR-539 and MMP-8 was analyzed by bioinformatics analysis and dual-luciferase reporter assays. Mouse xenograft model was further established to examine the therapeutic effects of the TP73-AS1 knockdown and miR-539 overexpression in vivo. RESULTS: We found TP73-AS1 and MMP-8 upregulation, and miR-539 downregulation in HCC tissues and cell lines. Lower TP73-AS1 and MMP-8 expressions and higher miR-539 expression were associated with higher survival rate of patients. M2-macrophage markers CD206, Arg-1 and CD163 were significantly upregulated in the tumor tissues. TP73-AS1 negatively and directly regulated miR-539 and knockdown of TP73-AS1 inhibited MMP-8 expression and M2 macrophage polarization. Also, overexpression of miR-539 suppressed M2 macrophage polarization by negatively regulating MMP-8. Furthermore, knockdown of MMP-8 also restrained M2 macrophage polarization via inhibiting TGF-ß1 signaling. We also found knockdown of TP73-AS1 or overexpression of miR-539 inhibited HCC tumor growth and M2 macrophage infiltration in vivo. CONCLUSION: Our study demonstrated lncRNA TP73-AS1 negatively regulated miR-539 to promote MMP-8 expression, which activated TGF-ß1 signaling to induce M2 macrophage polarization in HCC.

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