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1.
Neuroscience ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33002559

RESUMO

Chylomicron Retention Disease (CMRD) is a rare inherited lipid malabsorption syndrome that exhibits a recessive hypocholesterolemia in infants. CMRD has been associated with genetic mutations of SAR1B-a member of the Arf GTPase family involved in the secretory pathway from the endoplasmic reticulum to the Golgi. CMRD patients suffer from multiple neurological deficits, the etiologies of which remain unclear. In this study, we found that Sar1b protein is expressed in developing mouse neocortex. The knockdown of Sar1b does not affect the proliferation and mitotic exit of the neural progenitors but inhibits the radial migration of the newborn cortical neurons. At postnatal day 3, the neurons stalled in the white matter fail to develop axons across the midline of the corpus callosum, resulting in the loss of the neurons later on. hSAR1B(D137N), a CMRD-associated mutant of SAR1B, also impairs the positioning of the cortical neurons in the mouse brain, suggesting a dominant-negative effect by the human heterozygous mutant. The results indicate that SAR1B is crucial to radial migration and axon morphogenesis of the cortical neurons. Our study reveals a cell-autonomous action of Sar1b, which is unrelated to lipid absorption from the gut, on the development of the cerebral cortex.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1474-1479, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067940

RESUMO

OBJECTIVE: To investigate the value of fluorescence in situ hybridization (FISH) in the diagnosis and prognosis evaluation of patients with chronic lymphocytic leukemia (CLL). METHODS: Ninty-three patients with newly diagnosed CLL were tested by five probes including RB1 (13q14.1), D13S25 (13q14.3), p53(17p13.1), ATM( 11q22.3) and CSP12, while conventional cytogenetics (CC) was used for karyotype analysis. Then the correlation of the molecular cytogenetic abnormalities with the clinical Binet stages, Rai stages and the other related laboratory examinations was analyzed. RESULTS: The detection rate of chromosome abnormality in 93 patients was 79.6%, out of which detection rate of 13q (13q- was the highest and accounted for 45.2%), followed by trisomy 12 (+12) 26.9%, p53 deletion (17p-) 19.4% and ATM deletion (11p-) 17.2%. There were 27 cases (29.0%) with 2 or more abnormalities, including 13 cases with 13q-/17q-, 5 with 13q-/11q-, and 4 with 13q-/+12. Compared with CC test results, the positive rate of FISH detection was significantly higher (χ2=32.127, P<0.01). There was no significant correlation between FISH results and Rai stages (P>0.05), meanwhile 17p- highly correlated with later stage of the Binet stages (P=0.012). The molecular cytogenetic abnormalities significantly correlated with age, absolute value of peripheral lymphocyte count and CD38 expression level (P>0.05). The incidence of 13q- in female (65.4%) was statistically significantly higher than that in male (37.3%) (P=0.015). The unmutated IGHV rate of CLL patients with a 17p- was significantly higher than that in patients without this genetic abnormality (P=0.013). The expression of CD38 was detected among 29.0% of the patients, which significantly correlated with Binet stages (P=0.027) and unmutated IGHV (P=0.006). CONCLUSION: FISH can greatly increase the detection rate of molecular cytogenetic abnormalities in CLL patients, which, as a powerful supplement to the conventional cytogenetics, can be applied for the clinical staging and prognosis evaluation of CLL patients.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1762-1768, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067987

RESUMO

OBJECTIVE: To investigate the effect of dasatinib on the expansion of NK cells in vitro, as well as the subsets, receptor expression and cytotoxic function of NK cells. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy adult volunteers and cultured with SCGM added IL-2 and IL-15 for expansion of NK cells. In this culture system, dasatinib of different concentrations were added. Cell counting and phenotyping by flow cytometry were used to evaluate the amplification efficiency of NK cells. FCM was used to detect the expression of receptors on the surface of NK cells and the distribution of subsets. Subsequently, degranulation assay and CFSE/7AAD based cytotoxicity assay were used to detect the effects of dasatinib on NK cytotoxicity against leukemia cell line K562 cells. RESULTS: The expansion efficiency of NK cells in vitro could be increased by dasatinib at the concentration range of 5-50 nmol/L, and the expansion efficiency of NK cells reached the peak at 20 nmol/L of dasatinib. The NK cytotoxicity against K562 cells in dasatinib cultured group at the concentration of 20 nmol/L was significantly higher than that in control group. For the cells cultured by disatinib in vitro, the MFI of CD226, NKP46 and NKG2D was up-regulated; the ratio of NKG2A+CD57- subset was down-regulated, while the ratio of NKG2A-CD57+ subset was up-regulated.The degranulation response of NKG2A-CD57+ NK cells to K562 cells was stronger than that of NKG2A+CD57- NK cells. CONCLUSION: The results shows that appropriate dose of dasatinib(20 nmol/L) can increases the amplification efficiency of NK cells, simultaneously up-regulates the expression of NK activating receptors and increases the NKG2A-CD57+ subset, which lead to the enhancement of NK cytotoxicty against leukemia cell lines.

4.
Aging (Albany NY) ; 122020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33040051

RESUMO

OBJECTIVES: To evaluate the fatal impact of COVID-19 on patients with comorbid cardiovascular disease (CVD). RESULTS: Overall, the 28-day mortality of patients with comorbid CVD was 3.25 times of that of patients without comorbid CVD (40.63% vs 12.50%, P=0.011). Clinic symptoms on admission were similar for the two groups. However, patients with comorbid CVD had higher levels of Interleukin-10 (22.22% vs 0%, P=0.034), procalcitonin (22.6% vs 3.13%, P<0.001), high-sensitivity troponin I (20 pg/mL vs 16.05 pg/mL, P=0.019), and lactic dehydrogenase (437 U/L vs 310 U/L, P=0.015). In addition, patients with comorbid CVD experienced a high incidence of acute respiratory distress syndrome (59.38% vs 15.63%, P<0.001), and required more invasive mechanical ventilation (40.63% vs 12.50%, P=0.011). Methylprednisolone was found to improve the survival of patients without comorbid CVD (p = 0.05). CONCLUSIONS: Comorbid CVD resulted in a higher mortality rate for COVID-19 patients. Acute respiratory distress syndrome was the primary reason of death for COVID-19 patients with comorbid CVD, followed by acute myocardial infarction. METHODS: This retrospective study used propensity score matching to divide 64 COVID-19 patients into two groups with and without comorbid CVD. Clinic symptoms, laboratory features, treatments, and 28-day mortality were compared between the two groups.

5.
Genes Genomics ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33040302

RESUMO

BACKGROUND: The overexpression of TSLP and DNA methylation in asthma were both risk factors the relationship was not clear. OBJECTIVE: This study aimed to investigate the relationship between methylation status of TSLP promoter and mRNA/protein expression in asthmatic airway epithelial cells. METHODS: Human bronchial epithelial cells were cultured in vitro and divided into: Control group, treated with PBS, model group, sensitized with LPS (10 µg/mL) for 12 h (37 °C, 5% CO2). Other groups were cultured with the pCMV3 plasmid (M + NC/pCMV), pGPH1 plasmid (M + NC/pGPH), DNMT1/pCMV3 plasmid (M + DNMT1/pCMV), and DNMT1/pGPH1 plasmid (M + DNMT1/pGPH) for 48 h. The expression of DNA methyltransferase 1 and TSLP were measured using real-time PCR and western blotting. RESULTS: Compared with the control group, TSLP mRNA (1.00 ± 0.00 vs. 2.82 ± 0.81 vs. 1, P < 0.001) and protein (1.07 ± 0.04 vs. 1.46 ± 0.11, P < 0.01) were significantly greater, and the methylation of promoter was lower (92.75 ± 1.26 vs. 58.57 ± 3.34, P < 0.05) in the model group. Compared with the model group, TSLP mRNA (2.82 ± 0.81 vs. 1.17 ± 0.10, P < 0.001) decreased, but TSLP promoter methylation increased (58.57 ± 3.34 vs. 92.58 ± 7.30, P < 0.05) in M + DNMT1/pCMV. TSLP mRNA and protein were higher (2.82 ± 0.81 vs. 5.32 ± 0.21, P < 0.001; 1.46 ± 0.11 vs. 1.94 ± 0.11, respectively, P < 0.01), TSLP promoter methylation was lower (58.57 ± 3.34 vs. 33.57 ± 4.29, P < 0.05) in M + DNMT1/pGPH. CONCLUSIONS: Overexpression of TSLP in asthmatic airway epithelial cells may be regulated by DNA demethylation.

6.
Ann Palliat Med ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-33040539

RESUMO

Benign metastasizing leiomyoma (BML) is a rare condition that occurs mainly in premenopausal women and is characterized most commonly by pulmonary metastases. Here, we report the case of a 45-yearold woman who presented with multiple bilateral pulmonary nodules on chest examination during a health checkup 13 years after myomectomy. This patient has a normal menstrual cycle, moderate anemia, and no obvious respiratory symptoms. Serum concentrations of cancer markers such as carcinoembryonic antigen, neuron specific enolase, cytokeratin 19 fragments, and pro-gastrin-releasing peptide were within normal limits. Color doppler ultrasound was also performed, several hypoechoic regions were found in uterine bodies and cavity. The computed tomography (CT)-guided lung biopsy was used for histopathological examination. Immunohistochemical staining revealed BML which were positive for smooth muscle antibody, desmin, vimentin, estrogen and progesterone receptors, and Ki-67 positive rate of about 1%. Hysterectomy and bilateral adnexectomy were performed as a part of treatment. The lung nodules were meticulously monitored at follow-up. Three months later, the repeat CT scan showed that the nodules had reduced in size, and no new nodules had appeared, 1 year later, CT scan showed no obvious changes in lung nodules. This study is of great significance as the results will be helpful in diagnosing and treating future pulmonary benign metastasizing leiomyoma (PBML) cases.

7.
Cell Mol Biol (Noisy-le-grand) ; 66(6): 93-97, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33040792

RESUMO

Lung cancer is a disease characterized by the uncontrolled growth of cells in lung tissue. If left untreated, cell growth can spread beyond the lungs to a process called metastasis and reach surrounding tissues or other organs. This experiment was set up to discuss and analyze the research value of joint detection of tumor markers including carcino-embryonic antigen (CEA), cytokeratin 19 fragments (CYFRA21-1) and neuron-specific enolase (NSE) in the diagnosis and pathological type of lung cancer. From November 2016 to February 2018, 378 cases of patients with lung cancer treated in our hospital and 200 cases of people with healthy physical examinations were collected. The electrochemical immunoluminescence method was adopted to detect the CEA, CYFRA21-1 and NSE. The detected positive rate and the concentration of CEA, CYFRA21-1 and NSE of lung cancer group were higher than that of the healthy physical examination group. The differences were of statistical significance (P<0.05); the detected positive rate of CEA and CYFRA21-1 and the concentration of CEA, CYFRA21-1 and NSE of squamous carcinoma group were higher than that of the adenocarcinoma group. The differences were of statistical significance (P<0.05). The CEA, CYFRA21-1 and NSE are related to the pathological type of lung cancer and can be regarded as related indicators to diagnose lung cancer.

8.
Zool Res ; : 1-29, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33045777

RESUMO

The emerging virus SARS-CoV-2 has caused a global pandemic, and understanding its pathogenesis and host antiviral immunity is critical for the development of vaccines and antivirals. Mice are frequently used to generate animal models of infectious diseases due to their convenience and ability to undergo genetic manipulation. However, normal adult mice are not susceptible to SARS-CoV-2. Here, we developed a viral receptor (human angiotensin-converting enzyme 2, hACE2) pulmonary transfection mouse model to rapidly establish SARS-CoV-2 infection in the mouse lung. Based on the model, the virus successfully infected the mouse lung after 2 days of transfection. Viral RNA/protein, innate immune cell infiltration, inflammatory cytokine expression, and pathological changes in the infected lung were observed after infection. Further studies indicated that neutrophils were the first and most abundant leukocytes that infiltrated the infected lung soon after viral infection. In addition, using infected CXCL5-knockout mice, the chemokine CXCL5 was found to be responsible for neutrophil recruitment. CXCL5 knockout decreased lung inflammation without diminishing viral clearance, suggesting a potential target for controlling pneumonia.

9.
Sci Rep ; 10(1): 16554, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024179

RESUMO

Tumor associated macrophages (TAMs) play a critical role in biology of various cancers, including breast cancer. In the current study, we defined "M1" macrophage and "M1"/"M2" ratio by transcriptomic signatures using xCell. We investigated the association between high level of "M1" macrophage or "M1"/"M2" ratio and the tumor immune microenvironment by analyzing the transcriptome of publicly available cohorts, TCGA and METABRIC. We found that "M1" high tumors were not associated with prolonged survival compared with "M1" low tumors, or with the response to neoadjuvant chemotherapy. "M1" high tumors were associated with clinically aggressive features and "M1" high tumors enriched the cell proliferation and cell cycle related gene sets in GSEA. At the same time, "M1" high tumors were associated with high immune activity and favorable tumor immune microenvironment, as well as high expression of immune check point molecules. Strikingly, all these results were mirrored in "M1"/"M2" ratio high tumors. In conclusion, transcriptomically defined "M1" or "M1"/"M2" high tumors were associated with aggressive cancer biology and favorable tumor immune microenvironment but not with survival benefit, which resembled only part of their conventional clinical characteristics.

10.
Cancers (Basel) ; 12(10)2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33036243

RESUMO

Pancreatic cancer is highly mortal due to uncontrolled cell proliferation. The G2M checkpoint pathway is an essential part of the cell cycle. We hypothesized that a high G2M pathway score is associated with cell proliferation and worse survival in pancreatic cancer patients. Gene set variation analysis using the Hallmark G2M checkpoint gene set was used as a score to analyze a total of 390 human pancreatic cancer patients from 3 cohorts (TCGA, GSE62452, GSE57495). High G2M score tumors enriched other cell proliferation genes sets as well as MKI67 expression, pathological grade, and proliferation score. Independent of other prognostic factors, G2M score was predictive of disease-specific survival in pancreatic cancer. High G2M tumor was associated with high mutation rate of KRAS and TP53 and significantly enriched these pathway gene sets, as well as high infiltration of Th2 cells. High G2M score consistently associated with worse overall survival in 3 cohorts, particularly in R1/2 resection, but not in R0. High G2M tumor in R1/2 highly enriched metabolic and cellular components' gene sets compared to R0. To our knowledge, this is the first study to use gene set variation analysis as a score to examine the clinical relevancy of the G2M pathway in pancreatic cancer.

11.
Sci Rep ; 10(1): 16239, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004887

RESUMO

High myopia (HM) is associated with impaired long-distance vision. accumulating evidences reported that abnormal visual experience leads to dysfunction in brain activity in HM even corrected. However, whether the long-term of abnormal visual experience lead to neuroanatomical changes remain unknown, the aim at this study is to investigate the alternation of cortical surface thickness in HM patients. 82 patients with HM (HM groups), 57 healthy controls (HC groups) were recruited. All participants underwent high-resolution T1 and resting-state functional magnetic resonance imaging (MRI) scans. The cortical thickness analysis was preformed to investigate the neuroanatomical changes in HM patients using computational anatomy toolbox (CAT 12) toolbox. Compare with HCs, HM patients showed decreased the cortical surface thickness in the left middle occipital gyrus (MOG), left inferior parietal lobule (IPL), right inferior temporal gyrus (ITG), right precuneus, right primary visual area 1 (V1), right superior temporal gyrus (STG), right superior parietal lobule (SPL), right occipital pole, and right the primary motor cortex (M1), and increased to the parietal operculum (OP4) (P < 0.01, FWE-corrected), the mean cortical thickness of right orbitofrontal cortex (OFC), right dorsolateral prefrontal cortex (DLPFC) and right subcallosal cortex showed negatively correlation between clinical variables (axis length (ALM), the average macular thickness (AMT), keratometer (KER) 1, KER2, the mean KER, the mean macular fovea thickness (MFK), the refractive diopter) in HM patients. Our result mainly provided an evidence of cortical thickness reduction and disconnection in visual center and visual processing area, and cortical thickness increase in left multimodal integration region in HM patients. This may provide important significance of the study of the neural mechanism of HM.

12.
Ann Hematol ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33000361

RESUMO

Prior studies have suggested that for leukemia patients with high-risk features, haplo-identical-hematopoietic stem cell transplantation (HID-HSCT) has a stronger anti-leukemia effect compared with HSCT using an identical sibling donor (ISD-HSCT). However, it is unclear whether an HID-HSC transplant also augments the graft-versus-leukemia (GVL) effect among refractory/relapsed (R/R) acute myeloid leukemia (AML) patients who are not in remission (NR). We conducted a retrospective analysis of 124 R/R AML patients with NR status who underwent HID-HSCT between April 2012 and December 2016 and compared these to 27 R/R AML patients who underwent an ISD-HSCT within the same timeframe. Among all of the patients, 68 (45.0%) had primary induction failure (PIF) and 83 (54.9%) were relapsed and had failed to respond to at least one cycle of salvage combination chemotherapy. Myeloablative conditioning regimens were administered to all patients. Here, we present a retrospective multivariate analysis of pre-transplantation risk factors and characteristics of all 151 patients and developed a predictive scoring system to predict patient survival. The median period of follow-up was 46 months for all patients. The HID cohort had a higher 5-year overall survival (OS) compared with the ISD cohort (48.6% ± 4.6% vs 25.9% ± 8.4, respectively; P = 0.017) and higher LFS (leukemia-free survival) (41.6% ± 7.5% vs 25.9% ± 8.4%, respectively; P = 0.019). There was no difference in the 5-year cumulative incidence of non-relapse mortality (NRM) (18.0% ± 3.8% and 34.9% ± 12.6%, respectively; P = 0.212) between the two group. However, the 5-year cumulative incidence of relapse (CIRs) was lower in the HID group compared with the ISD group (55.4% ± 8.9% vs 67.3% ± 9.9%, respectively; P = 0.021). Multivariate analysis showed three risk factors associated with OS and LFS: (1) ISD-HSCT, (2) use of a standardized conditioning regimen, and (3) less than 50% proportional reduction of blast cells in the bone marrow (BM). Based on these three risk factors, we developed a predictive scoring system for R/R AML patients undergoing HSCT. Patients who had a predictive score of 0 and 1 had a 66.6% ± 4.5% and 44.1% ± 3.6% OS rate at 5 years, respectively. Patients with a score ≥ 2 had only a 4.4 ± 0.2% OS rate at 5 years. An HID-HSCT had a better anti-leukemia effect among R/R AML patients with an NR status compared with an ISD-HSCT. We also identified pre-transplantation risk factors to delineate subgroups that could derive maximal benefit from HSCT.

13.
Clin Cardiol ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33002216

RESUMO

BACKGROUND: Although successful ablation of the accessory pathway (AP) eliminates atrial fibrillation (AF) in some of patients with Wolff-Parkinson-White (WPW) syndrome and paroxysmal AF, in other patients it can recur. HYPOTHESIS: Whether adding pulmonary vein isolation (PVI) after successful AP ablation effectively prevents AF recurrence in patients with WPW syndrome is unknown. METHODS: We retrospectively studied 160 patients (102 men, 58 women; mean age, 46 ± 14 years) with WPW syndrome and paroxysmal AF who underwent AP ablation, namely 103 (64.4%) undergoing only AP ablation (AP group) and 57 (35.6%) undergoing AP ablation plus PVI (AP + PVI group). Advanced interatrial block (IAB) was defined as a P-wave duration of >120 ms and biphasic (±) morphology in the inferior leads, using 12-lead electrocardiography (ECG). RESULTS: During the mean follow-up period of 30.9 ± 9.2 months (range, 3-36 months), 22 patients (13.8%) developed AF recurrence. The recurrence rate did not differ in patients in the AP + PVI group and AP group (15.5% vs 10.5%, respectively; P = .373). Univariable and multivariable Cox regression analyses showed that PVI was not associated with the risk of AF recurrence (hazard ratio, 0.66; 95% confidence interval, 0.26-1.68; P = .380). In WPW patients with advanced IAB, the recurrence rate was lower in patients in the AP + PVI group vs the AP group (90% vs 33.3%, respectively; P = .032). CONCLUSIONS: PVI after successful AP ablation significantly reduced the AF recurrence rate in WPW patients with advanced IAB. Screening of a resting 12-lead ECG immediately after AP ablation helps identify patients in whom PVI is beneficial.

14.
J Affect Disord ; 279: 53-58, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33038700

RESUMO

BACKGROUND: With the modification of DSM-5 mixed features specifier, a brief scale to screen mixed features in patients with mood disorders is needed in clinical practice. This study aimed to explore the psychometric properties of the Chinese version of the Clinically Useful Depression Outcome Scale supplemented with DSM-5 Mixed subtype (CUDOS-M-C) for the Chinese patients with mood disorders. METHODS: Overall, 300 patients with major depressive episode were recruited. All participants were assessed using CUDOS-M-C, Young Mania Rating Scale, Hamilton Anxiety Scale and Montgomery-Asberg Depression Rating Scale. The receiver operating characteristic (ROC) curve analysis was used to calculate the optimal cut-off values of CUDOS-M-C score. The reliability and validity of CUDOS-M-C were examined using Cronbach's alpha, intraclass correlation coefficient (ICC) and principal component analysis (PCA). RESULTS: The results of PCA indicated two-factor structure as the best solution for CUDOS-M-C, which explained 54.82% of cumulative variance. The Cronbach's alpha was 0.892 and the ICC was 0.853. The area under the ROC curve of the CUDOS-M-C for participants with mixed depression was 0.927 (p<0.001) and the suitable cut-off value was 8, with a sensitivity of 91.6% and specificity of 79.9%. LIMITATIONS: Most of the patients were recruited from eastern China and further research with larger sample is warranted. And this study did not perform confirmatory factor analysis to identify the generalization of factor structure of CUDOS-M-C. Besides, the study performed the test-retest reliability of CUDOS-M-C and further analysis is needed to ascertain the patient's post-treatment changes. CONCLUSION: The CUDOS-M-C demonstrated to have satisfactory psychometric properties as a self-report scale, and could be applied to screen patients with mixed depression in clinical practice.

15.
Int J Mol Sci ; 21(18)2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32933189

RESUMO

Angiogenesis is one of the hallmarks of cancer. We hypothesized that intra-tumoral angiogenesis correlates with inflammation and metastasis in breast cancer patients. To test this hypothesis, we generated an angiogenesis pathway score using gene set variation analysis and analyzed the tumor transcriptome of 3999 breast cancer patients from The Cancer Genome Atlas Breast Cancer (TCGA-BRCA), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), GSE20194, GSE25066, GSE32646, and GSE2034 cohorts. We found that the score correlated with expression of various angiogenesis-, vascular stability-, and sphingosine-1-phosphate (S1P)-related genes. Surprisingly, the angiogenesis score was not associated with breast cancer subtype, Nottingham pathological grade, clinical stage, response to neoadjuvant chemotherapy, or patient survival. However, a high score was associated with a low fraction of both favorable and unfavorable immune cell infiltrations except for dendritic cell and M2 macrophage, and with Leukocyte Fraction, Tumor Infiltrating Lymphocyte Regional Fraction and Lymphocyte Infiltration Signature scores. High-score tumors had significant enrichment for unfavorable inflammation-related gene sets (interleukin (IL)6, and tumor necrosis factor (TNF)α- and TGFß-signaling), as well as metastasis-related gene sets (epithelial mesenchymal transition, and Hedgehog-, Notch-, and WNT-signaling). High score was significantly associated with metastatic recurrence particularly to brain and bone. In conclusion, using the angiogenesis pathway score, we found that intra-tumoral angiogenesis is associated with immune reaction, inflammation and metastasis-related pathways, and metastatic recurrence in breast cancer.

16.
Anticancer Drugs ; 31(9): 918-924, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32889895

RESUMO

The hypoxic microenvironment is commonly found in various solid tumors including pancreatic ductal adenocarcinoma (PDAC). Saururus chinensis is a medicinal Chinese herb widely used because of documented anti-inflammatory and anti-angiogenic properties. Sauchinone is special active lignin extracted from S. chinensis and its biological functions have been extensively explored. Recent studies have found that sauchinone could affect tumor initiation, metastasis and progression of some cancers. However, the specific role of sauchinone in PDAC remains to be elucidated. The main aim of this study was to elucidate the involvement of sauchinone in the progression of PDAC under the hypoxic condition. The human PDAC cell lines PANC-1 and BxPC-3 were exposed to hypoxia and various concentrations of sauchinone. The CCK-8 assay was performed to detect cytotoxic effects of sauchinone on PDAC cells. The levels of vascular endothelial growth factor, hypoxia-inducible factor-1α, E-cadherin, N-cadherin, Wnt3a and ß-catenin were examined by the western blot analysis. Wound healing and transwell assays were used to assess cell migration and invasion. The results showed that the migratory and invasive abilities of PDAC cells were enhanced after exposure to hypoxia and the expression of epithelial-mesenchymal transition markers was also significantly regulated by hypoxia. All these effects induced under the hypoxic condition were terminated by sauchinone treatment. In addition, sauchinone suppressed hypoxia-induced activation of the Wnt/ß-catenin signaling pathway. Our study provided important insight into understanding the mechanisms of the anti-cancer effect of sauchinone. Taken together, we suggested that sauchinone may be considered a new therapeutic agent for PDAC treatment.

17.
J Zhejiang Univ Sci B ; 21(9): 727-739, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32893529

RESUMO

BACKGROUND AND OBJECTIVE: Acute liver failure (ALF) is a type of disease with high mortality and rapid progression with no specific treatment methods currently available. Glucocorticoids exert beneficial clinical effects on therapy for ALF. However, the mechanism of this effect remains unclear and when to use glucocorticoids in patients with ALF is difficult to determine. The purpose of this study was to investigate the specific immunological mechanism of dexamethasone (Dex) on treatment of ALF induced by lipopolysaccharide (LPS)/D-galactosamine (D-GaIN) in mice. METHODS: Male C57BL/6 mice were given LPS and D-GaIN by intraperitoneal injection to establish an animal model of ALF. Dex was administrated to these mice and its therapeutic effect was observed. Hematoxylin and eosin (H&E) staining was used to determine liver pathology. Multicolor flow cytometry, cytometric bead array (CBA) method, and next-generation sequencing were performed to detect changes of messenger RNA (mRNA) in immune cells, cytokines, and Kupffer cells, respectively. RESULTS: A mouse model of ALF can be constructed successfully using LPS/D-GaIN, which causes a cytokine storm in early disease progression. Innate immune cells change markedly with progression of liver failure. Earlier use of Dex, at 0 h rather than 1 h, could significantly improve the progression of ALF induced by LPS/D-GaIN in mice. Numbers of innate immune cells, especially Kupffer cells and neutrophils, increased significantly in the Dex-treated group. In vivo experiments indicated that the therapeutic effect of Dex is exerted mainly via the glucocorticoid receptor (Gr). Sequencing of Kupffer cells revealed that Dex could increase mRNA transcription level of nuclear receptor subfamily 4 group A member 1 (Nr4a1), and that this effect disappeared after Gr inhibition. CONCLUSIONS: In LPS/D-GaIN-induced ALF mice, early administration of Dex improved ALF by increasing the numbers of innate immune cells, especially Kupffer cells and neutrophils. Gr-dependent Nr4a1 upregulation in Kupffer cells may be an important ALF effect regulated by Dex in this process.

18.
J Biomater Sci Polym Ed ; : 1-16, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32896222

RESUMO

In this study, an ideal nano-scale material, named epidermal stimulating (ES) factors-gelatin/polycaprolactone (GT/PCL) nanofiber, was fabricated using a coaxial electrospinning technique. The ES-GT/PCL nanofibers possessed a highly porous structure with qualified mechanical properties for transplantation. With ES factors stored in the core and GT/PCL in the shell, the ES factors could be protected and released in a sustained manner. After seeding L929 cell line on ES-GT/PCL nanofibers for 7 days in vitro, the proliferation of cells was nearly 1.5 folds compared to the control group. The in vivo study showed that ES-GT/PCL nanofibers can accelerate skin wound healing rate during the healing course, especially on the early stage. The epidermal and dermal thickness, as well as skin appendages and fat tissue, were the most similar to the native skin. These findings provided valuable insights into the addition of multiple bioactive factors to nanometre biomaterials, and optimising the advantages of the compositions as a promising potential dermal substitute construct.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32897502

RESUMO

OBJECTIVES: Single-port thoracoscopic lobectomy is a new therapeutic technique for patients with lung cancer; however, insufficient data are available regarding its clinical outcomes. We therefore compared the clinical outcomes of single-port and two-port thoracoscopic lobectomies for lung cancer. METHODS: We retrospectively analyzed and compared the data of 204 and 368 patients with lung cancer who underwent single-port or two-port thoracoscopic lobectomy, respectively, between October 2014 and October 2017 at our institution. Patients in both groups underwent 1:1 propensity score matching, and 400 patients (200 patients in each group) were included. Perioperative clinical indicators were analyzed, including operation time, lymph node dissection stations and numbers, incidence of postoperative complications, and pain scores at 24 h, 72 h, and 1 week after surgery. RESULTS: No perioperative deaths occurred in either group. The operation time, intraoperative blood loss, chest drainage duration, duration of postoperative hospital stay, lymph node dissection station and number, rate of conversion to open surgery, number of ruptured intraoperative pulmonary vessel, and incidence of postoperative complications were not significantly different between the groups (all P > 0.05). However, analysis of the 24-h (P = 0.005), 72-h (P = 0.011), and 1-week (P = 0.034) visual analog scale score after surgery revealed that the postoperative pain levels were significantly lower in the single-port than in the two-port group. CONCLUSIONS: Single-port and two-port thoracoscopic lobectomies had similar perioperative outcomes, although the postoperative pain was lower after single-port than two-port thoracoscopic lobectomy. Hence, we concluded that single-port thoracoscopic lobectomy is an effective, minimally invasive, and promising surgical procedure.

20.
Comput Math Methods Med ; 2020: 8741739, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908583

RESUMO

Neonatal sepsis is one of the most prevalent causes of death of the neonates. However, the mechanisms underlying neonatal sepsis remained unclear. The present study identified a total of 1128 upregulated mRNAs and 1008 downregulated mRNAs, 28 upregulated lncRNAs, and 61 downregulated lncRNAs in neonatal sepsis. Then, we constructed PPI networks to identify key regulators in neonatal sepsis, including ITGAM, ITGAX, TLR4, ITGB2, SRC, ELANE, RPLP0, RPS28, RPL26, and RPL27. lncRNA coexpression analysis showed HS.294603, LOC391811, C12ORF47, LOC729021, HS.546375, HNRPA1L-2, LOC158345, and HS.495041 played important roles in the progression of neonatal sepsis. Bioinformatics analysis showed DEGs were involved in the regulation cellular extravasation, acute inflammatory response, macrophage activation of NF-kappa B signaling pathway, TNF signaling pathway, HIF-1 signaling pathway, Toll-like receptor signaling pathway, and ribosome, RNA transport, and spliceosome. lncRNAs were involved in regulating ribosome, T cell receptor signaling pathway, RNA degradation, insulin resistance, ribosome biogenesis in eukaryotes, and hematopoietic cell lineage. We thought this study provided useful information for identifying novel therapeutic markers for neonatal sepsis.

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