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1.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(1): 1-9, 2020 Feb 18.
Artigo em Chinês | MEDLINE | ID: mdl-32071456

RESUMO

OBJECTIVE: To identify the role of Tribbles pseudokinase 3 (TRIB3) during the process of adipogenic differentiation of human adipose-derived mesenchymal stem cells (hASCs), and to provide a new target and a novel idea for the application of hASCs in adipose tissue engineering and soft tissue regeneration. METHODS: TRIB3-knockdown hASCs (shTRIB3) and TRIB3-overexpression hASCs (TRIB3-over) were established using lentivirus transfection technique. The transfection effect was estimated by the visible presence of green fluorescence as the expression of green fluorescent protein (GFP) in the transfected hASCs. The lentiviral transfection efficiency was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. After adipogenic induction, Oil Red staining and quantification, as well as qRT-PCR about several specific adipogenic markers were used to evaluate the adipogenic differentiation ability of hASCs. RESULTS: In TRIB3-knockdown hASCs, the TRIB3 mRNA expression level decreased by about 84.3% compared with the control group (P<0.01), and the TRIB3 protein level also showed obvious reduction. Oppositely, in TRIB3-overexpression hASCs, the TRIB3 mRNA expression level increased by approximately 160% compared with the control group (P<0.01), and the TRIB3 protein level also showed a significant increase. These results indicated a successful construction of TRIB3-knockdown hASCs and TRIB3-overexpression hASCs. The Oil Red staining results showed that the down-regulation of TRIB3 significantly promoted lipid droplets formation in hASCs, consistent with Oil Red quantification. On the other hand, the up-regulation of TRIB3 suppressed lipid droplets formation in hASCs, consistent with Oil Red quantification. After adipogenic induction, adipogenesis-related genes, including peroxisome proliferator-activated receptor γ (PPARγ), cluster of differentiation 36 (CD36) and CCAAT/enhancer binding protein α (C/EBPα), were increased significantly in TRIB3-knockdown hASCs compared with the control group (P<0.01). Oppositely, PPARγ, CD36 and lipoprotein lipase (LPL) were significantly decreased in TRIB3-overexpression hASCs compared with the control group (P<0.01). CONCLUSION: TRIB3 inhibited the adipogenic differentiation of hASCs. Knockdown of TRIB3 promoted the ability of adipogenesis of hASCs, while overexpression of TRIB3 inhibited the adipogenic differentiation of hASCs. Considering the important role of PPARγ in the adipogenis process, the molecular mechanism of the regulatory function of TRIB3 may be related with PPARγ signal pathway.


Assuntos
Adipogenia , Células-Tronco Mesenquimais , Tecido Adiposo , Células Cultivadas , Humanos
2.
Eur Rev Med Pharmacol Sci ; 23(23): 10324-10331, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31841187

RESUMO

OBJECTIVE: Oral squamous cell carcinoma (OSCC), the most frequent head and neck cancer, has a high potential for metastasis. MiR-126 plays an important role in the tumorigenesis of many tumors; however, there were little studies in OSCC. The purpose of our study was to explore how miR-126 and ADAM9 worked on migration and invasion in OSCC. PATIENTS AND METHODS: The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was applied to detect the mRNA level of miR-126 and ADAM9. The transwell assay was utilized to calculate the migratory and invasive capacities in the OSCC cells. The luciferase report assay was utilized to verify that ADAM9 was a direct target of miR-126. RESULTS: MicroR-126 was downregulated in OSCC tissues and cell lines SCC25 and HSC3. ADAM9 was predicted to be a direct target of miR-126 and was upregulated in the OSCC cells. In addition, miR-126 suppressed the migratory and invasive ability via mediating the expression of ADAM9 by directly targeting its mRNA 3'-noncoding region (UTR), whose partial functions was reversed by ADAM9. CONCLUSIONS: MiR-126 inhibited the migratory and invasive capacities of OSCC by directly targeting the 3'-UTR of ADAM9 mRNA. It is suggested that miR-126/ADAM9 axis may play an essential role in inhibiting the abilities of migration and invasion in oral squamous cell carcinoma cells.

3.
Artigo em Chinês | MEDLINE | ID: mdl-31163529

RESUMO

Objective:To explore the relationships between glucocorticoid (GC) sensitivity and the prognosis of refractory sudden sensorineural hearing loss (SSNHL), and to analyze the related factors being affected the prognosis of SSNHL. Method:Ninety-one refractory SSNHL patients were enrolled in the present investigation. Peripheral blood mononuclear cells (PBMCs) from the refractory SSNHL were extracted to conduct GC proliferation dexamethasone (DEX) inhibition experiments. All patients accepted comprehensive treatment with methylprednisolone. Result:Total effective rate was 40.66% in refractory SSNHL patients. Gender, number of affected ear, age, accompanying with vertigo, tinnitus or not and the procedure of methylprednisolone treatment were irrelevant to the efficacy. Only the inhibitory rate of DEX and the time from onset to visit were related to GC treatment effect, especially for inhibitory rate of DEX. The DEX inhibition rate of the effective group was higher than that of the ineffective group. Conclusion:DEX inhibition rate can predict GC sensitivity and prognosis of SSNHL. GC sensitivity and the time from onset to treatment are two important factors affecting the prognosis of refractory SSNHL patients..


Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Anti-Inflamatórios/administração & dosagem , Dexametasona/administração & dosagem , Perda Auditiva Neurossensorial/complicações , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Súbita/complicações , Perda Auditiva Súbita/diagnóstico , Humanos , Leucócitos Mononucleares , Prognóstico , Zumbido , Vertigem
4.
J Nutr Health Aging ; 23(6): 547-551, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31233076

RESUMO

OBJECTIVES: We aimed to explore the association between serum UA and cellular aging markers. DESIGN: The current cross-sectional analysis was based on data collected within a type 2 diabetes project. SETTINGS: Serum uric acid (UA), which has both antioxidant and pro-oxidant properties, is thought to be involved in cellular aging processes. PARTICIPANTS: There are 536 participants included in total, 65.3% of which are women. The average serum UA in women was 267.8 umol/l, lower than in men of 337.7 umol/l (P<0.001). MEASUREMENTS: Serum UA, blood lipid profile, HbA1c, plasma glucose and insulin were determined. The peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) were assessed using a real-time PCR assay. Logistic regressions were used to analyze the associations between serum UA and cellular aging markers. RESULTS: In Spearman's correlation analysis, there were significantly negative correlations between serum UA and LTL in both women and men (r=-0.162, P=0.006; and r=-0.232, P=0.004, respectively). The logistic regression adjusted for age, BMI, WC, daily energy intake, HbA1c, TG, and LDL-C revealed that the ORs of shorter LTL comparing the extreme serum UA quintiles was 5.52 (95% CI 1.69-18.02; P for trend =0.025) in women and 6.49 (95% CI 1.38-30.45; P for trend =0.108) in men. Furthermore, the OR (95% CI) for shorter LTL per 1 SD increment in serum UA was 1.51(1.10-2.07) in women and 1.64(1.01-2.65) in men. In regard to mtDNAcn, the association between elevated serum UA and lower mtDNAcn only reached significance in men when comparing the second and fifth quintiles with reference quintile (OR=3.73(1.07-13.04) and 3.76(1.01-14.09) , separately, and P for trend=0.066). CONCLUSIONS: Our results indicate a significant negative association between serum UA and peripheral blood cellular aging markers. Serum UA might play a role in promoting cellular aging.

5.
Int J Oral Maxillofac Surg ; 48(4): 475-479, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30037668

RESUMO

The aim of this study was to explore whether botulinum toxin A (BTXA) injection treats epiphora secondary to submandibular gland (SMG) transplantation for severe keratoconjunctivitis sicca. Fifteen patients with epiphora after SMG transplantation were separated to three groups, and received 15U, 20U and 25U BTXA injection in the transplanted SMG, respectively. Secretion of transplanted SMG was assessed subjectively by visual analogue scale (VAS) regarding epiphora, and objectively by Schirmer test. There were no significant differences in the 15-U BTXA group regarding the values of the VAS on epihora before and 1 month after BTXA injection. While in 20-U group and 25-U group, the values of VAS on epihora decreased significantly after BTXA injection, and lasted for 6months. Under resting conditions, the secretion of transplanted SMG decreased 64.4%, 73.0% and 78.0% in 15-U, 20-U and 25-U groups, respectively (P<0.01), in 1month after BTXA injection; significant secretion decreasing lasted 3months only in the 25-U BTXA group. BTXA injection can decrease the secretion of transplanted SMG significantly, relieving the symptoms of epiphora; 25U BTXA is a suitable dose to treat 'opportunistic epiphora' after SMG transplantation.


Assuntos
Toxinas Botulínicas Tipo A , Ceratoconjuntivite Seca , Doenças do Aparelho Lacrimal , Humanos , Glândula Submandibular , Transplante Autólogo
6.
Int J Oral Maxillofac Surg ; 48(1): 40-47, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30057239

RESUMO

We assessed long-term outcomes of autologous microvascular submandibular gland (SMG) transplantation for severe dry eye disease and investigated factors influencing long-term results. From August 1999 to January 2015, 185 patients (200 eyes) with severe dry eye received SMG transplantation. Subjective assessments and ophthalmologic evaluations were performed before and after transplantation. Follow-up results showed successful transplantation in 180 of 200 eyes (success rate: 90%), resulting in marked symptomatic relief of xerophthalmia. Surgery failed due to vascular thrombosis (15 glands) and duct obstruction (5 glands). Follow-up data were available for 163 eyes. Epiphora occurred in 98 (60.1%) eyes and was effectively managed by surgical reduction of graft, topical atropine gel and botulinum toxin injection. Wharton's duct obstruction occurred in 16 (10.6%) eyes and was treated by duct reconstruction. Subjective satisfaction was achieved in 143 (87.7%) eyes. Mean score of fluorescent staining reduced from 11.25±1.42 to 7.25±3.37. Postoperative best-corrected visual acuity improved in 85 (56.3%) eyes. Our clinical experience proved that SMG transplantation is effective and grants long-term improvement in severe dry eye. Secretory function of transplanted SMGs remains active and stable. Blood vessel thrombosis, Wharton's duct obstruction, and epiphora are primary factors influencing results.


Assuntos
Ceratoconjuntivite Seca/cirurgia , Glândula Submandibular/transplante , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Microcirurgia , Pessoa de Meia-Idade , Satisfação do Paciente , Complicações Pós-Operatórias , Transplante Autólogo , Resultado do Tratamento , Acuidade Visual
7.
Eur Rev Med Pharmacol Sci ; 22(7): 1948-1957, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29687848

RESUMO

OBJECTIVE: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, which is the leading cause of cancer-related morbidity and mortality worldwide. The carbon monoxide-releasing molecules (CO-RMs) are transition metal carbonyls with the capacity to release carbon monoxide (CO). The aims of our study were to assess the effects and underlying mechanisms of CO-releasing molecules-2 (CORM-2) on proliferation, migration, invasion and apoptosis in NSCLC cells, and to evaluate its potential application for lung cancer. MATERIALS AND METHODS: NSCLC cells Calu-3 were treated with CORM-2, negative control and blank control. Cell proliferation, migration and invasion were assessed by cell Counting Kit-8 (CCK-8), scratch assay and matrigel invasion chamber experiment, respectively. Apoptosis was measured by flow cytometry. Real-time PCR and Western blot were applied to examine the expression of apoptosis-related molecules on mRNA and protein levels. RESULTS: CORM-2 markedly attenuated proliferation, migration and invasion of Calu-3 cells. CORM-2 treatment also significantly reduced the ratio of B cell lymphoma 2 (Bcl-2)/B cell lymphoma 2 associated X protein (Bax) while increased expression of caspase-3 and cytochrome c. The optimal dose of CORM-2 for Calu-3 cells was 100 µM. CONCLUSIONS: CORM-2 modulates biological functions of NSCLC cells and may provide a novel therapeutic strategy for lung cancer.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Compostos Organometálicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/patologia , Invasividade Neoplásica
8.
J Appl Microbiol ; 124(5): 1131-1138, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29446192

RESUMO

AIMS: (i) To obtain and identify the predatory bacteria for the control of contaminated bacteria and to promote the autotrophic growth of Chlorella USTB-01. (ii) To identify and measure the different cell numbers in microalgal culture using flow cytometer. METHODS AND RESULTS: A predatory bacterial strain was isolated using Escherichia coli BL21 as a sole prey host, which was identified as Bdellovibrio USTB-06 by the analysis of 16S rDNA sequence. A flow cytometer was successfully used to identify and measure the cell numbers of Chlorella USTB-01, the contaminated bacteria and Bdellovibrio USTB-06 simultaneously in the autotrophic culture of Chlorella USTB-01 according to the identification of the different cell sizes. With the addition of Bdellovibrio USTB-06 at initial 104 plaque-forming units per ml, the contaminated bacteria severely decreased by about five counts (in log10  CFU per ml) and the growth of Chlorella USTB-01 was greatly increased by 37·0% compared with those of control respectively. CONCLUSIONS: Bdellovibrio USTB-06 could effectively promote the growth of Chlorella USTB-01 via the killing of the contaminated bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study reveals a good biotechnology method to increase the growth of Chlorella USTB-01 which is very important in the industry of microalgal culture.


Assuntos
Bdellovibrio/fisiologia , Chlorella/crescimento & desenvolvimento , Chlorella/microbiologia , Processos Autotróficos , Bdellovibrio/isolamento & purificação , Escherichia coli/fisiologia , Interações Microbianas
9.
Beijing Da Xue Xue Bao Yi Xue Ban ; 50(1): 1-4, 2018 Feb 18.
Artigo em Chinês | MEDLINE | ID: mdl-29483714

RESUMO

Severe dry eye is a refractory ophthalmologic disease. Our multidisciplinary research group treated severe dry eye by microvascular autologous transplantation of submandibular gland (SMG) during the past 20 years. The SMG, with its blood vessels and Wharton's duct, was harvested from the submandibular triangle and transferred to the temporal area. The blood vessels in the SMG were anastomosed with the temporal blood vessels using a microsurgical technique. Then, the distal end of Wharton's duct was sutured to form an opening in the upper lateral conjunctival fold. The tear was replaced by the secretion of the transplanted SMG to lubricate the ocular surface. In our study, the surgical techniques of blood vessel management were continuously modified to increase the survival rate of the transplanted SMG. A novel surgical modality of partial transplantation of SMG was established to prevent postoperative epiphora. A clinical study with the largest case number in the world was conducted and the effectiveness of transplantation of SMG for severe dry eye was fully confirmed. In order to resolve two main clinical problems including ductal obstruction resulted from low secretion rate during the latent period, and epiphora due to over secretion of the transplanted SMG in the later term of transplantation, the regulation of the secretion mechanism of the normal and transplanted SMG were investigated. New opinions on mechanisms of saliva secretion were provided. Based on the priniciple of translational medicine, the results of related basic research were applied in the clinic. The clinical guidelines for secretion regulation of transplanted SMG were established. A concept of chronic obstructive sialadenitis of transplanted SMG was provided and its diagnostic criteria, diagnostic technique of sialography, and therapeutic regimen were established. As a result, the surgical success rate was obviously elevated, the surgical complications were decreased, and life quality of the patients was greatly improved.


Assuntos
Doenças do Aparelho Lacrimal , Glândula Submandibular , Transplante Autólogo , Humanos , Doenças do Aparelho Lacrimal/terapia , Ductos Salivares , Glândula Submandibular/transplante , Lágrimas
10.
J Mycol Med ; 28(1): 36-44, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29477784

RESUMO

OBJECTIVE: The aim of this study was to investigate the antifungal activity of dracorhodin perchlorate (DP) against planktonic growth and virulence factors of Candida albicans. METHODS: Microdilution method based on CLSI-M27-A3 was used to test the antifungal susceptibility of DP. The activity of DP against biofilm formation and development of C. albicans was quantified by XTT assay and visualized by confocal laser scanning microscope. The effect of DP on the morphological transition of C. albicans induced by four kinds of hyphal-inducing media at 37°C for 4hours was observed under microscope. The rescue experiment by adding exogenous cAMP analog was performed to investigate the involvement of cAMP in the yeast to hyphal transition and biofilm formation of C. albicans. Egg yolk emulsion agar was used to determine the inhibition of DP on the phospholipase production of C. albicans. Human JEG-3 and HUVEC cell lines, as well as the nematode Caenorhabditis elegans was used to assess the toxicity of DP. RESULTS: The minimum inhibitory concentration (MIC) of DP is 64µM while the antifungal activity was fungistatic. As low as a concentration at 16µM, DP could inhibit the yeast to hyphal transition in liquid RPMI-1640, Spider, GlcNAc and 10% FBS-containing Sabouroud Dextrose medium, as well as on the solid spider agar. Exogenous cAMP analog could rescue part of biofilm viability of C. albicans. DP could inhibit the production of phospholipase. The toxicity of DP against human cells and C. elegans is low. CONCLUSION: DP could inhibit the planktonic growth and virulent factors in multiple stages, such as yeast to hyphal transition, adhesion, biofilm formation and production of phospholipase of C. albicans.


Assuntos
Antifúngicos/farmacologia , Benzopiranos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Hifas/efeitos dos fármacos , Animais , Antifúngicos/administração & dosagem , Antifúngicos/toxicidade , Benzopiranos/administração & dosagem , Benzopiranos/toxicidade , Caenorhabditis elegans/efeitos dos fármacos , Candida albicans/enzimologia , Candida albicans/crescimento & desenvolvimento , Candida albicans/patogenicidade , Linhagem Celular Tumoral , Humanos , Testes de Sensibilidade Microbiana , Fosfolipases/efeitos dos fármacos , Virulência/efeitos dos fármacos , Fatores de Virulência
11.
Oncogene ; 37(1): 128-138, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-28892048

RESUMO

Pancreatic cancer is among the deadliest malignancies; however, the genetic events that lead to pancreatic carcinogenesis in adults remain unclear. In vivo models in which these genetic alterations occur in adult animals may more accurately reflect the features of human cancer. In this study, we demonstrate that inactivation of Cdkn2b (p15ink4b) is necessary for induction of pancreatic cancer by oncogenic KRASG12D expression and inactivation of Tp53 and Cdkn2a in adult mouse pancreatic ductal cells (P60 or older). KRASG12D overexpression in these cells activated transforming growth factor-ß signaling and expression of CDKN2B, which, along with CDKN2A, led to cellular senescence and protected cells from KRAS-mediated transformation via inhibition of retinoblastoma phosphorylation. These results show a critical role of CDKN2B inactivation in pancreatic carcinogenesis, and provide a useful adult animal model by genetic engineering via lentiviral delivery.


Assuntos
Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/genética , Animais , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Senescência Celular/genética , Inibidor de Quinase Dependente de Ciclina p15/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p18/genética , Inibidor de Quinase Dependente de Ciclina p18/metabolismo , Engenharia Genética/métodos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , RNA Interferente Pequeno/administração & dosagem , Proteína do Retinoblastoma/metabolismo , Deleção de Sequência , Proteína Supressora de Tumor p53/genética
12.
Psychol Med ; 48(1): 115-122, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28625224

RESUMO

BACKGROUND: Auditory verbal hallucinations (AVHs) are one of the most common and severe symptoms of schizophrenia, but the neuroanatomical abnormalities underlying AVHs are not well understood. The present study aims to investigate whether AVHs are associated with cortical thinning. METHODS: Participants were schizophrenia patients from four centers across China, 115 with AVHs and 93 without AVHs, as well as 261 healthy controls. All received 3 T T1-weighted brain scans, and whole brain vertex-wise cortical thickness was compared across groups. Correlations between AVH severity and cortical thickness were also determined. RESULTS: The left middle part of the middle temporal gyrus (MTG) was significantly thinner in schizophrenia patients with AVHs than in patients without AVHs and healthy controls. Inferences were made using a false discovery rate approach with a threshold at p < 0.05. Left MTG thickness did not differ between patients without AVHs and controls. These results were replicated by a meta-analysis showing them to be consistent across the four centers. Cortical thickness of the left MTG was also found to be inversely correlated with hallucination severity across all schizophrenia patients. CONCLUSION: The results of this multi-center study suggest that an abnormally thin left MTG could be involved in the pathogenesis of AVHs in schizophrenia.


Assuntos
Alucinações/patologia , Esquizofrenia/complicações , Esquizofrenia/patologia , Lobo Temporal/patologia , Adulto , Estudos de Casos e Controles , China , Feminino , Alucinações/etiologia , Humanos , Imagem por Ressonância Magnética , Masculino , Lobo Temporal/diagnóstico por imagem , Adulto Jovem
13.
Oncogene ; 37(8): 1062-1074, 2018 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-29106390

RESUMO

Glycolysis is critical for cancer stem cell reprogramming; however, the underlying regulatory mechanisms remain elusive. Here, we show that pyruvate dehydrogenase kinase 1 (PDK1) is enriched in breast cancer stem cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH+ subpopulations, decreases stemness-related transcriptional factor expression, and inhibits sphere-formation ability and tumor growth. Conversely, high levels of PDK1 enhance BCSC properties and are correlated with poor overall survival. In mouse xenograft tumor, PDK1 is accumulated in hypoxic regions and activates glycolysis to promote stem-like traits. Moreover, through screening hypoxia-related long non-coding RNAs (lncRNAs) in PDK1-positive tissue, we find that lncRNA H19 is responsible for glycolysis and BCSC maintenance. Furthermore, H19 knockdown decreases PDK1 expression in hypoxia, and ablation of PDK1 counteracts H19-mediated glycolysis and self-renewal ability in vitro and in vivo. Accordingly, H19 and PDK1 expression exhibits strong correlations in primary breast carcinomas. H19 acting as a competitive endogenous RNA sequesters miRNA let-7 to release Hypoxia-inducible factor 1α, leading to an increase in PDK1 expression. Lastly, aspirin markedly attenuates glycolysis and cancer stem-like characteristics by suppressing both H19 and PDK1. Thus, these novel findings demonstrate that the glycolysis gatekeeper PDK1 has a critical role in BCSC reprogramming and provides a potential therapeutic strategy for breast malignancy.


Assuntos
Neoplasias da Mama/patologia , Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/fisiopatologia , Células-Tronco Neoplásicas/patologia , Proteínas Serina-Treonina Quinases/metabolismo , RNA Longo não Codificante/genética , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Proliferação de Células , Feminino , Glicólise , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/metabolismo , Prognóstico , Proteínas Serina-Treonina Quinases/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Reprod Domest Anim ; 53(1): 3-10, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29134682

RESUMO

Several oocyte-derived genes/proteins are essential to early embryonic development. The expression and stability of these proteins are influenced by the autocrine/paracrine activity of factors released by oocytes and cumulus cells. This study investigated the paracrine and autocrine activity of follistatin (FS), which is secreted by oocytes and cumulus cells as part of porcine embryogenesis. Immunohistochemical (IHC) localization of follistatin was conducted on 100 randomly selected early- and late-cleaving two-cell embryos. Dissociated cumulus cells were treated with various doses of follistatin for determination of the follistatin gene (FST) mRNA expression levels by quantitative real-time PCR analysis. Microinjection of siRNA induced a downregulation of FST mRNA during embryonic development, thereby decreasing the proportion embryos developing to the blastocyst stage (19.33%). Immunolocalization analysis showed enhanced staining for follistatin in early-cleavage stage embryos. Quantitative real-time PCR indicated a significantly lower FST transcript level in cumulus cells after application of the highest dose of follistatin (100 ng/ml). Exogenous follistatin treatment of in vitro maturation embryos resulted in statistically significant dose-dependent changes during development. Application of the highest concentration (100 ng/ml) of follistatin decreased the maturation rate of the oocytes. On the other hand, the application of 10 ng/ml follistatin resulted in an increase in the number of embryos. The observed differential effect of exogenous follistatin might be due to maternal FST and autocrine/paracrine factors secreted by cumulus cells.


Assuntos
Células do Cúmulo/efeitos dos fármacos , Folistatina/farmacocinética , Oócitos/efeitos dos fármacos , Suínos/embriologia , Animais , Comunicação Autócrina , Blastocisto , Células do Cúmulo/metabolismo , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Folistatina/genética , Expressão Gênica , Inativação Gênica , Técnicas de Maturação in Vitro de Oócitos/veterinária , Oócitos/metabolismo , Comunicação Parácrina , RNA Mensageiro , Reação em Cadeia da Polimerase em Tempo Real , Suínos/genética , Suínos/metabolismo
15.
Oncogene ; 37(8): 1119, 2018 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-29251717

RESUMO

This corrects the article DOI: 10.1038/onc.2017.368.

16.
Eur Rev Med Pharmacol Sci ; 21(20): 4680-4686, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29131274

RESUMO

OBJECTIVE: To investigate the level of expression and the clinical significance of IL-2 (interleukin-2), IL-6 (interleukin-6) and TGF-ß (transforming growth factor-ß) in elderly patients with goiter and hyperthyroidism. PATIENTS AND METHODS: Gender, age, course of disease, BMI (Body Mass Index), serum FT3 (Free triiodothyronine-3), FT4 (Free triiodothyronine-4), TT3 (Total triiodothyronine-3), TT4 (Total triiodothyronine-4), TSH (Thyroid Stimulating Hormone) and clinical manifestations on admission and other general clinical data and laboratory examination results were collected and statistically analyzed as case group in 128 elderly patients with goiter and hyperthyroidism. Additional 128 over 60-year-old patients with hyperthyroidism were selected as control group. The thyroid tissue of these patients and the control group were examined by fine needle aspiration biopsy. The expressions of IL-2, IL-6, TGF-ß of the thyroid tissue in all patients were detected by immunohistochemistry, qRT-PCR (Real-time Quantitative Polymerase Chain Reaction) and Western blot method respectively, and the statistical analysis was carried out. p < 0.05 indicated that the difference had statistical significance. RESULTS: Compared with the control group, the expressions of IL-2, IL-6 and TGF-ß in the group of patients were significantly higher (p < 0.05). The significantly higher expression of IL-2, IL-6, and TGF-ß was mainly concentrated in the thyroid follicular cells of patients with hyperthyroidism and thyroid enlargement (p < 0.05). In the patients with goiter, hyperthyroidism, and symptoms of exophthalmos, the level of expression of IL-6 was significantly higher than that of patients without exophthalmos (p < 0.05). In the patients with goiter, hyperthyroidism and symptoms of exophthalmos, and the patients with goiter, hyperthyroidism without symptoms of exophthalmos, IL-2 and TGF-ß expression level were not different (p > 0.05). CONCLUSIONS: The expression levels of IL-2, IL-6, and TGF-ß were significantly increased in the patients with senile goiter and hyperthyroidism, but in the senile patients with goiter, hyperthyroidism and exophthalmos symptoms, IL-6 levels were significantly higher than those without exophthalmos. The use of IL-2, IL-6, and TGF-ß is of great significance in the diagnosis of goiter with hyperthyroidism, especially for elderly patients with atypical clinical symptoms of hyperthyroidism.


Assuntos
Bócio/diagnóstico , Hipertireoidismo/diagnóstico , Interleucina-2/metabolismo , Interleucina-6/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Idoso , Estudos de Casos e Controles , Feminino , Bócio/metabolismo , Humanos , Hipertireoidismo/metabolismo , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Glândula Tireoide/metabolismo , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue
17.
Eur Rev Med Pharmacol Sci ; 21(21): 4867-4874, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29164575

RESUMO

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide. Long non-coding RNAs (lncRNAs) are novel proposed non-coding RNAs, and play critical roles in tumorigenesis. However, the clinical significance, biological role and molecular mechanism of ncRNAs in HCC still remain largely elusive. The aim of this study was to uncover the clinical value and biological role of XLOC_010235 (XLOC), which has been demonstrated as an oncogene in gastric cancer, in HCC. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (QRT-PCR) was conducted to measure the level of XLOC in HCC tissues and cell lines. The relationship between XLOC expression and clinicopathological features of HCC patients was analyzed. Then loss-of-function assays were conducted to determine the biological effect of XLOC in HCC cells. RESULTS: Our investigations revealed that XLOC was increased in HCC tissues and cell lines, and high level of XLOC was significantly correlated with poor prognosis. Additionally, silenced XLOC significantly inhibited cell proliferation, induced cell apoptosis and facilitated cell migration of HCC in vitro. CONCLUSIONS: Our findings advance our understanding of the role of XLOC as an oncogene in HCC, which may help in the development of new therapeutics.


Assuntos
Carcinogênese/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , RNA Longo não Codificante/genética , Apoptose , Carcinoma Hepatocelular/diagnóstico , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Regulação para Cima
18.
Eur Psychiatry ; 45: 6-13, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28728097

RESUMO

BACKGROUND: The catechol-O-methyltransferase (COMT) gene is related to dopamine degradation and has been suggested to be involved in the pathogenesis of major depressive disorder (MDD). However, how this gene affects brain function properties in MDD is still unclear. METHODS: Fifty patients with MDD and 35 cognitively normal participants underwent a resting-state functional magnetic resonance imaging scan. A voxelwise and data-drive global functional connectivity density (gFCD) analysis was used to investigate the main effects and the interactions of disease states and COMT rs4680 gene polymorphism on brain function. RESULTS: We found significant group differences of the gFCD in bilateral fusiform area (FFA), post-central and pre-central cortex, left superior temporal gyrus (STG), rectal and superior temporal gyrus and right ventrolateral prefrontal cortex (vlPFC); abnormal gFCDs in left STG were positively correlated with severity of depression in MDD group. Significant disease×COMT interaction effects were found in the bilateral calcarine gyrus, right vlPFC, hippocampus and thalamus, and left SFG and FFA. Further post-hoc tests showed a nonlinear modulation effect of COMT on gFCD in the development of MDD. Interestingly, an inverted U-shaped modulation was found in the prefrontal cortex (control system) but U-shaped modulations were found in the hippocampus, thalamus and occipital cortex (processing system). CONCLUSION: Our study demonstrated nonlinear modulation of the interaction between COMT and depression on brain function. These findings expand our understanding of the COMT effect underlying the pathophysiology of MDD.


Assuntos
Catecol O-Metiltransferase/genética , Transtorno Depressivo Maior/genética , Hipocampo/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Adulto , Transtorno Depressivo Maior/fisiopatologia , Feminino , Hipocampo/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Córtex Pré-Frontal/patologia
19.
Artigo em Chinês | MEDLINE | ID: mdl-28614922

RESUMO

Objective: To investigate the efficacy and safety of the recombinant human tumor necrosis factor receptor Ⅱ-IgG Fc fusion protein (rhTNFR: Fc, etanercept) for the treatment of occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) . Methods: In September 2011 to February 2016, 12 patients with OMLDT were treated with etanercept 25 mg, subcutaneous injection, twice per week, doubling of first dose. The course of treatment was 6 weeks. The drug eruption area and severity index (DASI) score, the proportion of patients achieving a 50%, 75% and 90% reduction in DASI (DASI50, DASI75, DASI90) and the serum level of TNF-α were used to assess the efficacy at different times. Adverse reactions were also recorded and evaluated. The results were statistically analyzed by nonparametric Friedman test and repetitive measurement ANOVA using the software SPSS19.0. Results: After 4 weeks treatment, the DASI score decreased form 56.33±7.02 to 0.50±0.91 (P<0.01) . The DASI50, DASI75 and DASI90 were all increased to 12 (100%) . The serum level of TNF-α decreased form (43.74±41.62) pg/ml to (3.03±0.47) pg/ml (P<0.01) . Statistically significant difference was observed from the above indexes. There were no adverse reactions in clinical application. Conclusion: Recombinant human tumor necrosis factor receptor Ⅱ-IgG Fc fusion protein may be a safe and effective drug in the treatment of OMLDT.


Assuntos
Dermatite Ocupacional/terapia , Imunoglobulina G/sangue , Receptores Tipo II do Fator de Necrose Tumoral/farmacologia , Tricloroetileno/toxicidade , Dermatite Ocupacional/diagnóstico , Humanos , Imunoglobulina G/farmacologia
20.
Clin. transl. oncol. (Print) ; 19(4): 425-431, abr. 2017. tab, ilus, graf
Artigo em Inglês | IBECS | ID: ibc-160891

RESUMO

Purpose. CD44v6 plays a controversial role in tumor progression and patient outcome in colorectal cancer by plenty of conflicting reports. The purpose of this study was to profile the intratumoral heterogeneity of CD44v6 in rectal cancer and investigate its role in lymph node metastasis. Methods. Sixty patients were included in this study. Immunohistochemistry for CD44v6 was performed in normal mucosa, primary tumor, and lymph node metastasis with whole tissue sections. The staining intensity in tumor center and invasive front was separately measured. Sampling bias was evaluated by quantitative real-time PCR with 15 pairs of frozen tissues from different sites of the primary tumor. Results. CD44v6 expression increased from normal mucosa to primary tumor to lymph node metastasis. Multiple intratumoral staining patterns was observed in primary tumor, and CD44v6 expression in invasive front was significantly higher than that in tumor center. In addition, mRNA expression levels differed across different geographical regions of the tumor. No association between CD44v6 expression and lymph node metastasis was revealed. Conclusions. Substantial intratumoral heterogeneity of CD44v6 exists in rectal cancer that impacts the outcome of individual studies. CD44v6 expression should be assessed in a more precise way with a specified staining pattern and in a designated location (AU)


No disponible


Assuntos
Humanos , Masculino , Feminino , Proteína Cofatora de Membrana/análise , Neoplasias Retais/diagnóstico , Neoplasias Retais/patologia , Imuno-Histoquímica/métodos , Imuno-Histoquímica , Metástase Linfática/diagnóstico , Metástase Linfática/patologia , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico
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