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1.
Cancer Imaging ; 20(1): 26, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252816

RESUMO

BACKGROUND: The Vesical Imaging-Reporting and Data System (VI-RADS) was created in 2018, and a 5-point VI-RADS scoring system was proposed to determine whether the muscularis of the bladder has been infiltrated by tumor tissues. PURPOSE: To verify the accuracy of the VI-RADS scoring system in predicting muscle-invasive bladder cancer and to explore its value in clinical application. MATERIALS AND METHODS: A total of 220 patients with bladder cancer who underwent multiparameter magnetic resonance imaging from January 2017 to June 2019 were selected. Then, two radiologists with equivalent qualifications gave their diagnoses of bladder tumors on T2-weighted imaging, diffusion-weighted imaging and dynamic contrast enhanced imaging. Meanwhile, the bladder tumor was also scored on the basis of the VI-RADS system; for multifocal tumors, the highest tumor load was selected for scoring. Furthermore, the final pathological results of the patients were unknown during the imaging diagnosis and scoring. Next, the VI-RADS score was compared with the pathological results after surgery, and the ability of the VI-RADS score to assess the degree of muscularis infiltration was finally analyzed. RESULTS: A total of 220 patients were included in our study, including 194 males and 26 females. Among them, the pathological results were 113 cases of muscle-invasive bladder cancer and 107 cases of non-muscle-invasive bladder cancer. The results showed that there was a positive correlation between the pathological results and VI-RADS score (r = 0.821, P < 0.05). The area under the receiver operating characteristic curve of the VI-RADS score was 0.960 (95% CI: 0.937, 0.983). When the VI-RADS score was above 3, the sensitivity, specificity and accuracy of predicting muscle-invasive bladder cancer were 82.3, 95.3 and 88.64%, respectively. CONCLUSION: The VI-RADS scoring system has good diagnostic value in predicting the degree of tumor invasion and can be used to guide clinical decision-making and management.

2.
Liver Int ; 40(4): 860-865, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31943701

RESUMO

Several studies show associations between gut bacterial dysbiosis and chronic liver diseases, but causative mechanisms are largely unclear. We recently identified cytolysin, a bacterial exotoxin expressed and secreted by Enterococcus faecalis to cause liver damage in the setting of alcohol-related liver disease. Cytolysin was increased and highly correlated with liver disease severity and mortality in alcoholic hepatitis patients. In this study, we investigated if faecal cytolysin-positivity can be linked to non-alcoholic fatty liver disease, a highly prevalent disease where new biomarkers and treatment targets are urgently needed. In contrast to what we observed in alcoholic hepatitis, only seven out of 96 non-alcoholic fatty liver disease patients were cytolysin-positive, and these patients did not have increased liver disease activity compared with cytolysin-negative patients. These results indicate that the association of cytolysin carriage with worse clinical outcome might be specific for alcoholic hepatitis.

3.
J Hepatol ; 72(3): 391-400, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31606552

RESUMO

BACKGROUND & AIMS: Alcohol-associated liver disease is a leading indication for liver transplantation and a leading cause of mortality. Alterations to the gut microbiota contribute to the pathogenesis of alcohol-associated liver disease. Patients with alcohol-associated liver disease have increased proportions of Candida spp. in the fecal mycobiome, yet little is known about the effect of intestinal Candida on the disease. Herein, we evaluated the contributions of Candida albicans and its exotoxin candidalysin in alcohol-associated liver disease. METHODS: C. albicans and the extent of cell elongation 1 (ECE1) were analyzed in fecal samples from controls, patients with alcohol use disorder and those with alcoholic hepatitis. Mice colonized with different and genetically manipulated C. albicans strains were subjected to the chronic-plus-binge ethanol diet model. Primary hepatocytes were isolated and incubated with candidalysin. RESULTS: The percentages of individuals carrying ECE1 were 0%, 4.76% and 30.77% in non-alcoholic controls, patients with alcohol use disorder and patients with alcoholic hepatitis, respectively. Candidalysin exacerbates ethanol-induced liver disease and is associated with increased mortality in mice. Candidalysin enhances ethanol-induced liver disease independently of the ß-glucan receptor C-type lectin domain family 7 member A (CLEC7A) on bone marrow-derived cells, and candidalysin does not alter gut barrier function. Candidalysin can damage primary hepatocytes in a dose-dependent manner in vitro and is associated with liver disease severity and mortality in patients with alcoholic hepatitis. CONCLUSIONS: Candidalysin is associated with the progression of ethanol-induced liver disease in preclinical models and worse clinical outcomes in patients with alcoholic hepatitis. LAY SUMMARY: Candidalysin is a peptide toxin secreted by the commensal gut fungus Candida albicans. Candidalysin enhances alcohol-associated liver disease independently of the ß-glucan receptor CLEC7A on bone marrow-derived cells in mice without affecting intestinal permeability. Candidalysin is cytotoxic to primary hepatocytes, indicating a direct role of candidalysin on ethanol-induced liver disease. Candidalysin might be an effective target for therapy in patients with alcohol-associated liver disease.

4.
Hepatology ; 71(2): 522-538, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31228214

RESUMO

Chronic alcohol consumption causes increased intestinal permeability and changes in the intestinal microbiota composition, which contribute to the development and progression of alcohol-related liver disease. In this setting, little is known about commensal fungi in the gut. We studied the intestinal mycobiota in a cohort of patients with alcoholic hepatitis, patients with alcohol use disorder, and nonalcoholic controls using fungal-specific internal transcribed spacer amplicon sequencing of fecal samples. We further measured serum anti-Saccharomyces cerevisiae antibodies (ASCA) as a systemic immune response to fungal products or fungi. Candida was the most abundant genus in the fecal mycobiota of the two alcohol groups, whereas genus Penicillium dominated the mycobiome of nonalcoholic controls. We observed a lower diversity in the alcohol groups compared with controls. Antibiotic or steroid treatment was not associated with a lower diversity. Patients with alcoholic hepatitis had significantly higher ASCA levels compared to patients with alcohol use disorder and to nonalcoholic controls. Within the alcoholic hepatitis cohort, patients with levels of at least 34 IU/mL had a significantly lower 90-day survival (59%) compared with those with ASCA levels less than 34 IU/mL (80%) with an adjusted hazard ratio of 3.13 (95% CI, 1.11-8.82; P = 0.031). Conclusion: Patients with alcohol-associated liver disease have a lower fungal diversity with an overgrowth of Candida compared with controls. Higher serum ASCA was associated with increased mortality in patients with alcoholic hepatitis. Intestinal fungi may serve as a therapeutic target to improve survival, and ASCA may be useful to predict the outcome in patients with alcoholic hepatitis.

5.
J Colloid Interface Sci ; 561: 696-707, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31767396

RESUMO

The synthesis of environmental-friendly metal-free photocatalysts has great significance in photocatalytic technology. In this work, we firstly report the successful synthesis of in situ epitaxial growth of g-C3N4 on carbon dots through a facile thermal polymerization technique. Characterization and density functional theory (DFT) calculations were conducted to clarify the structure engineering and the electronic/chemical properties of the in-plane interconnected carbon dots/g-C3N4 (C-CN) heterostructures. With the optimal carbon dots content, the C-CN exhibited 3.2 times higher degradation rate for sulfadiazine (SDZ) than that of g-C3N4. Besides, the C-CN heterostructures displayed excellent stability and reusability in five consecutive cycles. The enhanced photocatalytic activity was related to the narrowed band gap and the local electronic density of valance band and conduction band orbitals of the unique plane heterostructures, corroborated by the spectroscopic characterizations and theoretical calculations. Photogenerated holes dominated the degradation of SDZ, while OH showed a negligible contribution. Moreover, DFT calculation succeeded to predict that the atoms with high Fukin index (f0) on SDZ molecule were more vulnerable to radicals attack. SDZ degradation pathway mainly included smiles-type rearrangement, SO2 extrusion, ring hydroxylation and SN bond cleavage processes. The eco-toxicity assessment revealed the generation of less toxic intermediates after photocatalysis. Our findings not only afford a new technique for constructing g-C3N4-based in-plane heterostructures with high and stable photocatalytic efficiency, but also highlight the feasible application of metal-free photocatalysts in environmental remediation.

6.
Nat Mater ; 19(1): 94-101, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31659291

RESUMO

Natural self-assembled three-dimensional photonic crystals such as blue-phase liquid crystals typically assume cubic lattice structures. Nonetheless, blue-phase liquid crystals with distinct crystal symmetries and thus band structures will be advantageous for optical applications. Here we use repetitive electrical pulses to reconfigure blue-phase liquid crystals into stable orthorhombic and tetragonal lattices. This approach, termed repetitively applied field, allows the system to relax between each pulse, gradually transforming the initial cubic lattice into various intermediate metastable states until a stable non-cubic crystal is achieved. We show that this technique is suitable for engineering non-cubic lattices with tailored photonic bandgaps, associated dispersion and band structure across the entire visible spectrum in blue-phase liquid crystals with distinct composition and initial crystal orientation. These field-free blue-phase liquid crystals exhibit large electro-optic responses and can be polymer-stabilized to have a wide operating temperature range and submillisecond response speed, which are promising properties for information display, electro-optics, nonlinear optics, microlasers and biosensing applications.

7.
J Cell Biochem ; 121(1): 672-689, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31407370

RESUMO

Papillary renal cell carcinoma (pRCC) is a heterogeneous disease containing multifocal or solitary tumors with an aggressive phenotype. Increasing evidence has indicated the involvement of aberrant splicing variants in renal cell cancer, while systematic profiling of aberrant alternative splicing (AS) in pRCC was lacking and largely unknown. In the current study, comprehensive profiling of AS events were performed based on the integration of pRCC cohort from the Cancer Genome Atlas database and SpliceSeq software. With rigorous screening and univariate Cox analysis, a total of 2077 prognoses AS events from 1642 parent genes were identified. Then, stepwise least absolute shrinkage and selection operator method-penalized Cox regression analyses with 10-fold cross-validation followed by multivariate Cox regression were used to construct the prognostic AS signatures within each AS type. And a final 21 AS event-based signature was proposed which showed potent prognostic capability in stratifying patients into low- and high-risk subgroups (P < .0001). Furthermore, time-dependent receiver operating characteristics curves confirmed that the final AS signature was effective and robust in predicting overall survival for pRCC patients with the area under the curve above 0.9 from 1 to 5 years. In addition, splicing correlation network was built to uncover the potential regulatory pattern among prognostic splicing factors and candidate AS events. Besides, gene set enrichment analysis revealed the involvement of these candidates AS events in tumor-related pathways including extracellular matrix organization, oxidative phosphorylation, and P53 signaling pathways. Taken together, our results could contribute to elucidating the underlying mechanism of AS in the oncogenesis process and broaden the novel field of prognostic and clinical application of molecule-targeted approaches in pRCC.

8.
Nature ; 575(7783): 505-511, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31723265

RESUMO

Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality1-3. Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated liver disease. The gut microbiota promotes ethanol-induced liver disease in mice4, but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin-a two-subunit exotoxin that is secreted by Enterococcus faecalis5,6-as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis. The presence of cytolysin-positive (cytolytic) E. faecalis correlated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis. We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecalis with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis.

9.
Oncol Rep ; 42(6): 2450-2472, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31578577

RESUMO

Alternative splicing (AS) is a pervasive and vital mechanism involved in the progression of cancer by expanding genomic encoding capacity and increasing protein complexity. However, the systematic analysis of AS in hepatocellular carcinoma (HCC) is lacking and urgently required. In the present study, genome­wide AS events with corresponding clinical information were profiled in 290 patients with HCC from the Cancer Genome Atlas and SpliceSeq software. Functional enrichment analyses revealed the pivotal biological process of AS regulation. Univariate Cox regression analyses were performed, followed by stepwise forward multivariate analysis to develop the prognostic signatures. Spearman's correlation analyses were also used to construct potential regulatory network between the AS events and aberrant splicing factors. A total of 34,163 AS events were detected, among which 1,805 AS events from 1,314 parent genes were significantly associated with the overall survival (OS) of patients with HCC, and their parent genes serve crucial roles in HCC­related oncogenic processes, including the p53 signaling pathway, AMPK signaling pathway and HIF­1 signaling pathway. A prognostic AS signature was established that was found to be an independent prognostic factor for OS in stratified cohorts, harboring a noteworthy ability to distinguish between the distinct prognoses of patients with HCC (high­risk vs. low­risk, 827 vs. 3,125 days, P<2e­16). Time­dependent receiver­-operator characteristic curves confirmed its robustness and clinical efficacy, with the area under the curves maintained >0.9 for short­term and long­term prognosis prediction. The splicing correlation network suggested a trend in the interactions between splicing factors and prognostic AS events, further revealing the underlying mechanism of AS in the oncogenesis of HCC. In conclusion, the present study provides a comprehensive portrait of global splicing alterations involved in the progression and HCC in addition to valuable prognostic factors for patients, which may represent as underappreciated hallmark and provide novel clues of therapeutic targets in HCC.

10.
Biochem Biophys Res Commun ; 519(2): 246-252, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31495492

RESUMO

BACKGROUND: Bladder cancer (BCa) is one of the most common urological malignancies. While Inositol-3-phosphate synthase 1 (ISYNA1) expression and function were largely unknown in BCa. We aimed to study the expression and role of ISYNA1 in bladder cancer and investigate its potential mechanisms via ingenuity pathway analysis (IPA). METHODS: ISYNA1 expression was quantified by qRT-PCR in bladder cancer cell lines as well as normal urothelial cell line. Knocking down ISYNA1 gene in BCa T24 cells was achieved by shRNA lentivirus transfection. MTT and Celigo assay were used to assess cell proliferation. Flow cytometry was applied to test cell cycle and apoptosis. In addition, IPA was performed using PrimeView™ Human Gene Expression Array. Imunohistochemistry (IHC) was performed in BCa patient tissue microarray to verify the association between ISYNA1 expression and patients' clinicopathological features. RESULTS: ISYNA1 was significantly upregulated in BCa samples vs. para-tumor tissues. Higher expression were significantly associated with tumor T stage and lymph node metastasis of bladder cancer patients. Similarly, it was elevated in BCa cell lines (5637 and T24) compared with SVHUC cells. Knocking down ISYNA1 significantly decreased proliferation, induced apoptosis and cell cycle arrest in T24 cells. Furthermore, IPA indicated that ISYNA1 was an important regulatory factors and related networks were involved in multiple functional processes. CONCLUSION: Taken together, current study suggest ISYNA1 promotes proliferation and inhibit apoptosis in bladder cancer cells, and its expression correlated with BCa patients' clinicopathological features. Thus, ISYNA1 may serve as a potential biomarker and therapeutic target for BCa patients.

11.
Oncogene ; 38(42): 6850-6866, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31406252

RESUMO

Increasing evidence has indicated that circular RNAs (circRNAs) play a critical role in cancer development. However, only a small number of circRNAs have been experimentally validated and functionally annotated. In this study, using a high-throughput microarray assay, we identified a novel circRNA, circKDM4C, which was downregulated in breast cancer tissues with metastasis. Furthermore, we analyzed a cohort of breast cancer patients and found that circKDM4C expression was decreased in breast cancer tissues, and lower circKDM4C expression was associated with poor prognosis and metastasis in breast cancer. Functionally, we demonstrated that circKDM4C significantly repressed breast cancer proliferation, metastasis, and doxorubicin resistance in vitro and in vivo. Mechanistically, using a dual-luciferase activity assay and AGO2 RNA immunoprecipitation, circKDM4C was identified as a miR-548p sponge. We also found that PBLD was a direct target of miR-548p, which functioned as a tumor suppressor in breast cancer. Moreover, miR-548p overexpression was able to reverse the circKDM4C-induced attenuation of malignant phenotypes and elevated expression of PBLD in breast cancer cells. Taken together, our data indicate that circKDM4C might have considerable potential as a prognostic biomarker in breast cancer, and support the notion that therapeutic targeting of circKDM4C/miR-548p/PBLD axis may be a promising treatment approach for breast cancer patients.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Doxorrubicina/farmacologia , Histona Desmetilases com o Domínio Jumonji/genética , MicroRNAs/metabolismo , Proteínas/metabolismo , Neoplasias da Mama/patologia , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Prognóstico
12.
Theranostics ; 9(14): 4030-4046, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281530

RESUMO

Heart diseases are one of the leading causes of death for humans in the world. Increasing evidence has shown that myocardial injury induced innate and adaptive immune responses upon early cellular damage but also during chronic phases post-injury. The immune cells can not only aggravate the injury but also play an essential role in the induction of wound healing responses, which means they play a complex role throughout the acute inflammatory response and reparative response after cardiac injury. This review will summarize the current experimental and clinical evidence of lymphocytes, one of the major types of immune cells, participate in heart diseases and try to explain the possible role of these immune cells following cardiac injury.

13.
Mol Ther Nucleic Acids ; 17: 347-361, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31302495

RESUMO

Emerging evidence suggests that circular RNAs (circRNAs) have crucial roles in various processes, including cancer development and progression. However, the functional roles of circRNAs in breast cancer remain to be elucidated. In this study, we identified a novel circRNA (named circBMPR2) whose expression was lower in breast cancer tissues with metastasis. Moreover, circBMPR2 expression was negatively associated with the motility of breast cancer cells and significantly downregulated in human breast cancer tissues. Functionally, we found that circBMPR2 knockdown effectively enhanced cell proliferation, migration, and invasion. Moreover, circBMPR2 knockdown promoted tamoxifen resistance of breast cancer cells through inhibiting tamoxifen-induced apoptosis, whereas circBMPR2 overexpression led to decreased tamoxifen resistance. Mechanistically, we demonstrated that circBMPR2 could abundantly sponge miR-553 and that miR-553 overexpression could attenuate the inhibitory effects caused by circBMPR2 overexpression. We also found that ubiquitin-specific protease 4 (USP4) was a direct target of miR-553, which functions as a tumor suppressor in breast cancer. Our findings demonstrated that circBMPR2 might function as a miR-553 sponge and then relieve the suppression of USP4 to inhibit the progression and tamoxifen resistance of breast cancer. Targeting this newly identified circRNA may help us to develop potential novel therapies for breast cancer patients.

14.
Dig Dis Sci ; 64(7): 1878-1892, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31076986

RESUMO

BACKGROUND: Alcohol-related liver disease is one of the most prevalent chronic liver diseases worldwide. Mechanisms involved in the pathogenesis of alcohol-related liver disease are not well understood. Oxylipins play a crucial role in numerous biological processes and pathological conditions. Nevertheless, oxylipins are not well studied in alcohol-related liver disease. AIMS: (1) To characterize the patterns of bioactive ω-3 and ω-6 polyunsaturated fatty acid metabolites in alcohol use disorder and alcoholic hepatitis patients and (2) to identify associations of serum oxylipins with clinical parameters in patients with alcohol-related liver disease. METHODS: We performed a comprehensive liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis of serum and fecal oxylipins derived from ω-6 arachidonic acid, ω-3 eicosapentaenoic acid, and docosahexaenoic acid in a patient cohort with alcohol-related liver disease. RESULTS: Our results show profound alterations in the serum oxylipin profile of patients with alcohol use disorder and alcoholic hepatitis compared to nonalcoholic controls. Spearman correlation of the oxylipins with clinical parameters shows a link between different serum oxylipins and intestinal permeability, aspartate aminotransferase, bilirubin, albumin, international normalized ratio, platelet count, steatosis, fibrosis and model for end-stage liver disease score. Especially, higher level of serum 20-HETE was significantly associated with decreased albumin, increased hepatic steatosis, polymorphonuclear infiltration, and 90-day mortality. CONCLUSIONS: Patients with alcohol-related liver disease have different oxylipin profiles. Future studies are required to confirm oxylipins as disease biomarker or to connect oxylipins to disease pathogenesis.


Assuntos
Alcoolismo/sangue , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Fezes/química , Hepatite Alcoólica/sangue , Oxilipinas/sangue , Adulto , Idoso , Alcoolismo/diagnóstico , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Feminino , Hepatite Alcoólica/diagnóstico , Humanos , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
15.
Front Genet ; 10: 278, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984247

RESUMO

Background: Increasing evidence indicated a close relationship between aberrant splicing variants and carcinoma, whereas comprehensive analysis of prognostic alternative splicing (AS) profiling in breast cancer (BRCA) is lacking and largely unknown. Methods: RNA-seq data and corresponding clinical information of BRCA patients were obtained and integrated from The Cancer Genome Atlas (TCGA). Then SpliceSeq software was used to assess seven AS types and calculate the Percent Spliced In (PSI) value. Univariate followed by stepwise multivariate Cox regression analyses identified survival associated AS events and constructed the AS signature, which were further sent for enrichment analysis, respectively. Besides, the splicing correlation network was constructed. Additionally, nomogram incorporating AS signature and clinicopathological characteristics was developed and its efficacy was evaluated with respect to discrimination, calibration and clinical utility. Results: A total of 45,421 AS events were detected, among which 3071 events were found associated with overall survival (OS) after strict filtering. Parent genes of these prognostic events were involved in BRCA-related processes including NF-kappaB and HIF-1 signaling pathway. Besides, the final prognostic signature built with 20 AS events performed well with an area under the curve (AUC) of receiver operating characteristic (ROC) curve up to 0.957 for 5 years. And gene set enrichment analysis (GSEA) also confirmed the candidate 20 AS events contributed to progression of BRCA. Moreover, the nomogram that incorporated 20-AS-event-based classifier, age, pathological stage and Her-2 status showed good calibration and moderate discrimination, with C-index of 0.883 (95% CI, 0.844-0.921). Decision curve analysis (DCA) confirmed more benefit was added to survival prediction with our nomogram, especially in 5 or 8 years with threshold probability up to 80%. Finally, splicing correlation network revealed an obvious regulatory pattern of prognostic splicing factors (SF) in BRCA. Conclusion: This study provided a systematic portrait of survival-associated AS events involved in BRCA and further presented a AS-clinicopathological nomogram, which could be conveniently used to assist the individualized prediction of long-term survival probability for BRCA patients. And a series of bioinformatic analysis provided a promising perspective for further uncovering the underlying mechanisms of AS events and validating therapeutic targets for BRCA.

16.
Zhen Ci Yan Jiu ; 44(3): 205-10, 2019 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-30945504

RESUMO

OBJECTIVE: To evaluate the effectiveness and safety of internal heat-type acupuncture needle (IHTAN) the-rapy in the treatment of post-stroke shoulder pain in apopletic patients. METHODS: According to the random number table, 96 patients with post-stroke shoulder pain were divided into IHTAN group and warm needle moxibustion group (n=48 in each one). Jianyu (LI15), Jianliao (TE14), Jianzhen (SI9), Binao (LI14) and Ashi points (Extra) on the affected side were selected in the two groups. For patients of the IHTAN group, internal warmth controllable acupuncture needles were inserted into the above-mentioned acupoints, and then connected to an internal heat acupuncture apparatus for stimulating the acupoints at 42 ℃, 20 min every time, once a week, for 4 weeks. For patients of the warm needle moxibustion group, the above mentioned acupoints were stimulated with filiform needles attached with an ignited moxa-stick, once every other day, for 4 weeks. If the shoulder pain disappeared or basically disappeared, it was considered to be healed, if the pain was relieved, it was considered to be effective, ot-herwise, it was considered to be ineffective. The incidence of local skin injury including burn, empyrosis, silt blue, hematoma and infection, the heart rate, respiration, blood pressure, oxyhemoglobin saturation, blood routine (hemoglobin level, white blood cell [WBC] count, platelet count), creatase and dipolymer levels were recorded or detected. Additionally, the patients' satisfaction rate about the treatment environment was recorded. RESULTS: Following the treatment, of the 45 and 47 cases in the warm needle moxibustion and IHTAN groups, 5 (11.11%) and 20 (42.55%) were cured, 26(57.78%) and 21(44.68%) experienced marked improvement, and 14 (31.11%) and 6 (12.77%) had no apparent changes in their shoulder pain severity, with the total effective rates being 68.89% and 87.23%, respectively. The curative rate and total effective rate of the IHTAN group were significantly higher than those of the warm needle moxibustion group (P<0.01,P<0.05). The incidence of skin injury of the IHTAN group was evidently lower than that of the warm needle moxibustion group (P<0.01), and the patients' therapeutic environment satisfaction rate was remarkably higher in the IHTNA group than in the warm needle moxibustion group (P<0.05). No significant differences were found between the two groups and between pre- and post-treatment in each group in the heart rate, respiration frequency, systolic and diastolic pressures, oxyhemoglobin saturation, hemoglobin content, WBC count, platelet count, and plasma dipolymer, creatine kinase, lactic dehydrogenase, and beta-hydroxybutyrate dehydrogenase levels (P>0.05). CONCLUSION: The IHTAN therapy is effective, safe and reliable in the treatment of post-stroke shoulder pain. In terms of the incidence of skin injury and the satisfaction degree of therapeutic environment, the internal heat-type acupuncture needle therapy is obviously superior to the warm needle moxibustion therapy.


Assuntos
Moxibustão , Acidente Vascular Cerebral , Pontos de Acupuntura , Temperatura Alta , Humanos , Agulhas , Dor de Ombro/terapia , Resultado do Tratamento
17.
Spectrochim Acta A Mol Biomol Spectrosc ; 218: 206-212, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-30995578

RESUMO

Hydrogen sulfide (H2S) is a kind of gaseous signal molecule in many physiological processes. In order to detect H2S, a novel "turn on" fluorescent probe 6,12-dihydroxyperylene-1,7-dione (DPD) was designed and synthesized. The probe DPD is fluorescence silence, while the addition of H2S induces an obvious green fluorescence with an obvious color change from dark blue to yellow-green. The probe shows excellent selectivity, fast response (2.5min) and linear curve (0-90µM) in wide effective pH range (4-10). Competition experiments are also revealed in corresponding studies and the detection limit is 3.6µM. The response mechanism is proved to be the reduction of the probe by H2S, which is confirmed by 1H NMR. Furthermore, through the fluorescence turn-on signal toward H2S in Hela cells, probe DPD was successfully applied to monitor H2S in living Hela cells.


Assuntos
Corantes Fluorescentes/química , Sulfeto de Hidrogênio/análise , Perileno/análogos & derivados , Quinonas/química , Fluorescência , Corantes Fluorescentes/síntese química , Células HeLa , Humanos , Limite de Detecção , Microscopia Confocal , Imagem Óptica , Perileno/síntese química , Perileno/química , Quinonas/síntese química , Espectrometria de Fluorescência
18.
Cancer Res ; 79(13): 3347-3359, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30940661

RESUMO

Triple-negative breast cancer (TNBC) is highly heterogeneous and has a poor prognosis. It is therefore important to identify the underlying molecular mechanisms in order to develop novel therapeutic strategies. Although emerging research has revealed long noncoding RNAs (lncRNA) as vital to carcinogenesis and cancer progression, their functional involvement in TNBC has not been well defined. In this study, we utilized the The Cancer Genome Atlas (TCGA) database and analyzed clinical samples to show that the long noncoding antisense transcript of nicotinamide phosphoribosyltransferase (NAMPT), NAMPT-AS, is upregulated in TNBC and is associated with poor prognosis, lymph node involvement, metastasis, and advanced stage. NAMPT-AS was cotranscribed with NAMPT from a bidirectional promoter, where the distributions of H3K4me3 and H3K27Ac chromatin modifications were enriched based on ENCODE and FANTOM5, suggesting the potential enhancer-RNA characteristics of NAMPT-AS. NAMPT-AS epigenetically regulated the expression of NAMPT in two divergent ways: NAMPT-AS recruited POU2F2 to activate the transcription of NAMPT, and NAMPT-AS acted as a competing endogenous RNA to rescue NAMPT degradation from miR-548b-3p. NAMPT-AS/NAMPT promoted tumor progression and regulated autophagy through the mTOR pathway in vitro and in vivo. In a cohort of 480 breast cancer patients, NAMPT was associated with breast cancer-specific survival and overall survival. These results demonstrate that NAMPT-AS is an oncogenic lncRNA in TNBC that epigenetically activates NAMPT to promote tumor progression and metastasis. Furthermore, these data identify NAMPT-AS/NAMPT as promising therapeutic targets in patients with TNBC. SIGNIFICANCE: Upregulation of the long noncoding antisense RNA of NAMPT gene (NAMPT-AS) is associated with metastasis and poor prognosis in TNBC.

19.
PLoS One ; 14(3): e0211491, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30822312

RESUMO

BACKGROUND: The present study aims to investigate the gene expression changes in papillary renal cell carcinoma(pRCC) and screen several genes and associated pathways of papillary renal cell carcinoma progression. METHODS: The papillary renal cell carcinoma RNA sequencing (RNA-seq) data set was downloaded from TCGA (The Cancer Genome Atlas). We identified the differentially expressed mRNAs between cancer and normal tissues and performed annotation of differentially expressed mRNAs to figure out the functions and pathways they were enriched in. Then, we constructed a risk score that relied on the 5-mRNA. The optimal value for the patients'classification risk level was identified by ROC analysis. The relationship between mRNA expression and prognosis of papillary renal cell carcinoma was evaluated by univariate Cox regression model. The 5-mRNA based risk score was validated in both complete set and testing set. RESULT: In general, the 5-mRNA (CCNB2, IGF2BP3, KIF18A, PTTG1, and BUB1) were identified and validated, which can predict papillary renal cell carcinoma patient survival. This study revealed the 5-mRNA expression profile and the potential function of a single mRNA as a prognostic target for papillary renal cell carcinoma. CONCLUSION: In addition, these findings may have significant implications for potential treatments options and prognosis for patients with papillary renal cell carcinoma.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Bases de Dados Genéticas , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Curva ROC , Fatores de Risco , Análise de Sequência de RNA , Transcriptoma/genética
20.
IUBMB Life ; 71(7): 928-941, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30907986

RESUMO

Nimotuzumab is a humanized anti-EGF monoclonal antibody that has been approved for treating different cancers. However, few studies have examined its therapeutic potential in prostate cancer (PC), a most common and highly aggressive malignancy among male population. We used both LNCaP, and PC3 and PC3-AR (androgen receptor) cells as the model system and assessed the effects of nimotuzumab on epithelial-mesenchymal transition (EMT) in vitro and in vivo. The EMT makers were detected by immunohistochemistry, qRT-PCR and Western blot. MTT, wound healing assay, and transwell assay were used to measure cell viability, migration, and invasion, respectively. For mechanistic understanding, we evaluated the significance of Akt/Y-box binding protein-1 (YB-1)/AR axis in nimotuzumab-induced EMT by overexpressing AR, activating Akt using SC79, and/or downregulating YB-1 using siRNA. Nimotuzumab suppressed the xenograft growth from both LNCaP and PC3 cells in vivo, which was associated with reduced EMT. Consistently, nimotuzumab inhibited proliferation, cell-cycle progression, EMT, and migration/invasion, but stimulated apoptosis of both LNCaP and PC3-AR cells in vitro. On the molecular level, nimotuzumab inactivated Akt and YB-1 and reduced the expression of AR. Boosting AR expression in LNCaP and PC3-AR cells antagonized the action of nimotuzumab, at least partially restored EMT, and enhanced the migration/invasion. We also found that Akt was essential for controlling YB-1 activation, and both critical for regulating the levels of AR and EMT-related biomarkers. In this study, we presented our novel findings that by targeting the Akt/YB-1/AR axis, nimotuzumab significantly inhibited EMT of PC cells. Considering that EMT is a critical mechanism contributing to the metastatic spread of cancer cells, nimotuzumab may become a promising therapy for alleviating the malignant progression of PC. © 2019 IUBMB Life, 1-14, 2019.

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