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1.
Zhonghua Zhong Liu Za Zhi ; 45(7): 594-604, 2023 Jul 23.
Artigo em Chinês | MEDLINE | ID: mdl-37462016

RESUMO

Objective: To explore the mechanism of Doublecortin-like kinase 1 (DCLK1) in promoting cell migration, invasion and proliferation in pancreatic cancer. Methods: The correlation between DCLK1 and Hippo pathway was analyzed using TCGA and GTEx databases and confirmed by fluorescence staining of pancreatic cancer tissue microarrays. At the cellular level, immunofluorescence staining of cell crawls and western blot assays were performed to clarify whether DCLK1 regulates yes associated protein1 (YAP1), a downstream effector of the Hippo pathway. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to analyze the expressions of YAP1 binding transcription factor TEA-DNA binding proteins (TEAD) and downstream malignant behavior-promoting molecules CYR61, EDN1, AREG, and CTGF. Transwell test of the DCLK1-overexpressing cells treated with the Hippo pathway inhibitor Verteporfin was used to examine whether the malignant behavior-promoting ability was blocked. Analysis of changes in the proliferation index of experimental cells used real-time label-free cells. Results: TCGA combined with GTEx data analysis showed that the expressions of DCLK1 and YAP1 molecules in pancreatic cancer tissues were significantly higher than those in adjacent tissues (P<0.05). Moreover, DCLK1was positively correlated with the expressions of many effectors in the Hippo pathway, including LATS1 (r=0.53, P<0.001), LATS2 (r=0.34, P<0.001), MOB1B (r=0.40, P<0.001). In addition, the tissue microarray of pancreatic cancer patients was stained with multicolor fluorescence, indicated that the high expression of DCLK1 in pancreatic cancer patients was accompanied by the up-regulated expression of YAP1. The expression of DCLK1 in pancreatic cancer cell lines was analyzed by the CCLE database. The results showed that the expression of DCLK1 in AsPC-1 and PANC-1 cells was low. Thus, we overexpressed DCLK1 in AsPC-1 and PANC-1 cell lines and found that DCLK1 overexpression in pancreatic cancer cell lines promoted YAP1 expression and accessible to the nucleus. In addition, DCLK1 up-regulated the expression of YAP1 binding transcription factor TEAD and increased the mRNA expression levels of downstream malignant behavior-promoting molecules. Finally, Verteporfin, an inhibitor of the Hippo pathway, could antagonize the cell's malignant behavior-promoting ability mediated by high expression of DCLK1. We found that the number of migrated cells with DCLK1 overexpressing AsPC-1 group was 68.33±7.09, which was significantly higher than 22.00±4.58 of DCLK1 overexpressing cells treated with Verteporfin (P<0.05). Similarly, the migration number of PANC-1 cells overexpressing DCLK1 was 65.66±8.73, which was significantly higher than 37.00±6.00 of the control group and 32.33±9.61 of Hippo pathway inhibitor-treated group (P<0.05). Meanwhile, the number of invasive cells in the DCLK1-overexpressed group was significantly higher than that in the DCLK1 wild-type group cells, while the Verteporfin-treated DCLK1-overexpressed cells showed a significant decrease. In addition, we monitored the cell proliferation index using the real-time cellular analysis (RTCA) assay, and the proliferation index of DCLK1-overexpressed AsPC-1 cells was 0.66±0.04, which was significantly higher than 0.38±0.01 of DCLK1 wild-type AsPC-1 cells (P<0.05) as well as 0.05±0.03 of DCLK1-overexpressed AsPC1 cells treated with Verteporfin (P<0.05). PANC-1 cells showed the same pattern, with a proliferation index of 0.77±0.04 for DCLK1-overexpressed PANC-1 cells, significantly higher than DCLK1-overexpressed PANC1 cells after Verteporfin treatment (0.14±0.05, P<0.05). Conclusion: The expression of DCLK1 is remarkably associated with the Hippo pathway, it promotes the migration, invasion, and proliferation of pancreatic cancer cells by activating the Hippo pathway.


Assuntos
Quinases Semelhantes a Duplacortina , Neoplasias Pancreáticas , Humanos , Via de Sinalização Hippo , Verteporfina/farmacologia , Linhagem Celular Tumoral , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Neoplasias Pancreáticas/patologia , Proteínas de Sinalização YAP , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Supressoras de Tumor/genética , Neoplasias Pancreáticas
2.
Zhonghua Yu Fang Yi Xue Za Zhi ; 57(5): 649-653, 2023 May 06.
Artigo em Chinês | MEDLINE | ID: mdl-37165812

RESUMO

Objective: To investigate the relationship between serum lysophosphatidylcholine (LPC) level and the health index of the elderly. Methods: A total of 251 subjects were selected from the 2016 baseline survey of the Yongfu Longevity Cohort in Guangxi Province among whom 66, 63 and 122 were in the young and middle-aged group (≤59 years old), the young group (60-89 years old) and the longevity group (≥90 years old), respectively. Demographic data were collected and related indicators of height, weight, blood pressure and lipid metabolism were measured. The cognitive and physical functions of the elderly were assessed by the results of the simple mental state scale and the daily living activity scale to construct the health index of the elderly. The serum levels of LPC16∶0, LPC18∶0, LPC18∶1 and LPC18∶2 were determined by liquid chromatography-tandem mass spectrometry, and the differences among different ages and health status groups were compared. The logistic regression model was used to analyze the relationship between the serum LPC level and the health index of the elderly. Results: With the increase in age, the proportion of female subjects increased, and the rate of smoking and drinking decreased. BMI, TC, TG, LDL-C, diastolic blood pressure, and the four LPCs levels decreased with the increase of age, and systolic blood pressure levels increased with the increase of age (all P values<0.05). There was no significant difference in HDL-C levels among age groups (P>0.05). With the decline of health status in the elderly, serum levels of LPC16∶0, LPC18∶0, LPC18∶1 and LPC18∶2 showed a downward trend (all P values<0.001). After adjusting for age and gender, only LPC18∶0 was associated with the health status in old age [OR (95%CI): 0.48 (0.25-0.92)]. For every 1 standard deviation (16.87 nmol/L) increase in serum LPC18∶0 concentration, the risk of poor health status in old age decreased by 52%. Conclusion: Serum LPC18∶0 was associated with the health status in old age independent of age and sex.


Assuntos
Longevidade , Lisofosfatidilcolinas , Idoso , Pessoa de Meia-Idade , Humanos , Feminino , Idoso de 80 Anos ou mais , Fatores de Risco , China , Inquéritos e Questionários , Triglicerídeos
3.
Zhonghua Yu Fang Yi Xue Za Zhi ; 57(5): 654-658, 2023 May 06.
Artigo em Chinês | MEDLINE | ID: mdl-37165813

RESUMO

International research on healthy life expectancy (HALE) focuses on inequality of socioeconomic status and individual natural attributes. With the acceleration of population ageing and the increase in average life expectancy, the extension of unhealthy life expectancy and the increase of social and economic burden caused by diseases have gradually attracted the attention of countries around the world. Therefore, the evaluation of disease factors affecting HALE is a meaningful direction in the future. This study introduces the development process and commonly used measurement methods of HALE. According to the definition of health from the Global Burden of Disease Study and World Health Organization, physical and mental diseases such as cardiovascular and cerebrovascular diseases, chronic respiratory diseases, diabetes, malignant tumors and depression were selected to summarize the impact of these diseases and pre-disease states on HALE. It is expected to provide a theoretical basis for the formulation of relevant public health policies and the improvement of quality of life in China.


Assuntos
Expectativa de Vida Saudável , Qualidade de Vida , Humanos , Expectativa de Vida , Causalidade , Classe Social
4.
Poult Sci ; 101(12): 102196, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36272234

RESUMO

The objective of this experiment was to compare the slaughter and cecectomy methods to determine amino acid (AA) digestibility of corn and soybean meal and their additivity in a corn-soybean meal diet. A completely randomized design was adopted to determine endogenous AA losses (EAAL) and AA digestibility in each of corn, soybean meal, and a corn-soybean meal diet using either slaughter or cecectomy methods. Each treatment contained 6 replicates with 3 chickens per replicate. The endogenous loss (EL) of histidine and glycine was lower and the EL of methionine and phenylalanine was greater when determined by slaughter vs. cecectomy (P < 0.05). The EL of arginine, isoleucine, leucine, lysine, methionine, phenylalanine, valine, alanine, aspartic acid, glutamic acid, and serine determined by slaughter were 1.2 to 3.2 times of those from cecectomy. The standard error (SE) of EL of 14 AA (excluding histidine and glycine) obtained by slaughter method was 2.1 to 9.6 times of those by cecectomy method. The apparent and standardized digestibility was not affected by methods for most AA except apparent digestibility of methionine, phenylalanine and glycine, and standardized digestibility of glycine in corn. The apparent and standardized digestibility of most AA except apparent digestibility of glycine and standardized digestibility of lysine, cysteine and glycine were less for slaughter versus cecectomy methods in soybean meal (P < 0.05). Using slaughter method resulted in reduced apparent digestibility of 15 AA (except glycine) and reduced standardized digestibility of 7 AA (arginine, isoleucine, leucine, valine, aspartic acid, glutamic acid, and proline) relative to cecectomy method (P < 0.05), but the standardized digestibility of glycine was greater when determined by slaughter vs. cecectomy methods in corn-soybean meal diet (P < 0.05). The mean value of SE of 16 AA digestibility in slaughter method was 2.9 times of that by cecectomy method. The apparent digestibility of 2 and 9 of 16 AA and the standardized digestibility of 15 and 7 of 16 AA were additive when using slaughter and cecectomy determinations, respectively. In conclusion, compared to the slaughter method, cecectomy method had less SE and EAAL but greater apparent digestibility of methionine and phenylalanine in corn, and the apparent digestibility of 15 AA (except glycine) in soybean meal and corn-soybean meal diet. Additivity in apparent and standardized AA digestibility was more inconsistent when determined with slaughter vs. cecectomy methods. These findings suggest that the cecectomy method is more suitable than the slaughter method to determine the digestibility of AA.


Assuntos
Aminoácidos , Galinhas , Animais , Galinhas/metabolismo , Aminoácidos/metabolismo , Fenômenos Fisiológicos da Nutrição Animal , Digestão , Ração Animal/análise , Plumas , Leucina/metabolismo , Isoleucina/metabolismo , Lisina/metabolismo , Ácido Glutâmico , Ácido Aspártico/metabolismo , Histidina/metabolismo , Dieta/veterinária , Zea mays/química , Glycine max/química , Glicina/metabolismo , Metionina/metabolismo , Fenilalanina/metabolismo , Valina/metabolismo , Arginina/metabolismo , Íleo/metabolismo
6.
Artigo em Chinês | MEDLINE | ID: mdl-35866275

RESUMO

Objective: To analyze the clinical features and surgical outcomes of petrous bone cholesteatomas (PBCs). Methods: Data from 39 PBCs patients treated in the Department of Otorhinolaryngology, Xijing Hospital from September 2011 to December 2017 were reviewed retrospectively, including 23 males, 16 femals, aged 12-71 years old, with the median age of 37. Clinical classifications, surgical methods, facial and hearing function, and intraoperative and postoperative complications were made summary analysis. Results: In this study, five patients were congenital PBCs and 34 patients were acquired PBCs. The common clinical symptoms were hearing loss (100%, 39/39), ear discharge/pus (89.7%, 35/39) and facial paralysis (46.2%, 18/39). According to Sanna's classification, 14 cases were supralabyrinthine, including three cases underwent transcochlear (TC) approach, six cases underwent transotic (TO) approach and five underwent translabyrinthine (TL) approach. 10 cases were infralabyrinthine, including eight cases underwent subtotal petrosectomy, one case underwent TO approach and one underwent TL approach.10 cases were massive, including seven cases underwent TC approach, three cases underwent TO approach. Five cases were infralabyrinthine-apical, including two cases underwent TC approach, two cases underwent TO approach, and one case underwent endoscope assisted infratemporal fossa type B. The degree of facial nerve (FN) dysfunction from high to low was massive (6/10), supralabyrinthine (8/14), infralabyrinthine-apical (2/5) and infralabyrinthine (2/10). 19 cases involved in facial nerve operation, three cases underwent FN decompression, four cases underwent FN rerouting, four cases underwent nerve grafting, and one case underwent facial-hypoglossal anastomosis. Preoperative FN involvement in 18 cases, and the FN function was improved in 14 cases after surgery. The improved rate of postoperative FN function was 77.8%. The bone conducted hearing retained 50.0% (14/28) postoperatively. Five cases with cerebrospinal fluid leak were managed by inserting free muscle plugs and cavity obliteration. Two cases with the cholesteatomas matrix involved the sigmoid sinus and the jugular bulb, and occlusion of the sigmoid sinus was performed. Postoperatively, two patients presented with synkinesis. The patients were followed up for 40 to 115 months, and there was no recurrence. Conclusions: There are no specific clinical manifestations for PBCs, thus, it is difficult in early diagnosis and treatment. According to Sanna's classification, preoperative FN and hearing function, the best surgical approach should be selected with minimal recurrences and perioperative morbidity.


Assuntos
Colesteatoma , Osso Petroso , Adolescente , Adulto , Idoso , Criança , Colesteatoma/cirurgia , Nervo Facial/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Osso Petroso/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
8.
Poult Sci ; 100(9): 101301, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34273651

RESUMO

This research was conducted to determine the effects of natural capsaicin extract (NCE) as an alternative to the antibiotic (chlortetracycline, CTC) on growth performance, antioxidant capacity, immune function, and meat quality of broiler chickens. A total of 168 one-day-old Arbor Acre male broiler chickens with an average weight of 46.4 ± 0.6 g were randomly allotted to 3 dietary treatments, with 7 replicates per treatment and 8 broilers per pen. These 3 dietary treatments included a corn-soybean meal basal diet (CON), a basal diet + 75 mg/kg CTC (CTC), and a basal diet + 80 mg/kg NCE (NCE). Broilers from the NCE group showed higher average daily gain compared to broilers from the CON group at all stages (P < 0.05). On d 42, NCE supplementation improved dietary nitrogen-corrected apparent metabolizable energy compared to nonsupplemented or CTC-supplemented diets (P < 0.05). The digestibility of organic matter and crude protein were higher in the NCE diet than in the CON or CTC diets (P < 0.05). Higher relative weight of bursa of Fabricius was observed in broilers fed NCE diets compared with CON (P < 0.05). Pancreatic trypsin and lipase activities were significantly increased in the NCE group compared with those in the CON group (P < 0.05). The value of lightness (L*) of breast muscles from broilers fed NCE diets was significantly lower compared to those fed CON diets (P < 0.05). Broilers fed NCE diets also had higher levels of serum total antioxidant capacity, glutathione peroxidase, superoxide dismutase, and lower levels of interleukin-1ß, and tumor necrosis factor-α compared with broilers fed CON diets (P < 0.05). The liver catalase activity of broilers was also significantly increased in the NCE group than the CON group (P < 0.05). In addition, broilers from NCE group had lower concentrations of serum urea-N, low-density lipoprotein cholesterol, and total cholesterol, and higher concentration of growth hormone compared with those from the CON group (P < 0.05). Therefore, we concluded that supplementation of 80 mg/kg of NCE in diets could improve growth performance, nutrient digestibility, antioxidant status, immune function, and meat quality in broilers.


Assuntos
Capsicum , Galinhas , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Antioxidantes , Dieta/veterinária , Suplementos Nutricionais , Imunidade , Carne/análise , Nutrientes , Extratos Vegetais/farmacologia
9.
Poult Sci ; 99(10): 4929-4938, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988529

RESUMO

This experiment was conducted to evaluate the effects of wheat bran (WB) and antibiotics on growth performance, intestinal immunity, barrier function, and microbial composition in broiler chickens. A total of 168 one-day-old male Arbor Acre chicks were allocated to 3 treatments consisting of 7 replicates with 8 birds per replicate. The 3 treatments were: an antibiotic-free control diet (control, CON), CON + 75 mg/kg chlortetracycline as an antibiotic growth promoter (AGP), and CON + 3% WB. Birds fed AGP and WB had greater (P < 0.05) ADG during days 1 to 21 and lower (P < 0.05) feed-to-gain ratio during each phase than those fed CON. The WB supplementation reduced (P < 0.05) serum concentrations of tumor necrosis factor-α and diamine oxidase activity compared with CON on both day 21 and 42. The AGP and WB supplementation decreased (P < 0.05) interleukin-1ß concentration in jejunal mucosa on day 21 and increased (P < 0.05) secretory immunoglobulin A concentration in jejunal mucosa on day 21 and 42. The relative expression of occludin in jejunal mucosa was upregulated (P < 0.05) in WB than in CON on day 21. Moreover, both AGP and WB supplementation upregulated (P < 0.05) the relative expression of zonula occludens-1 in jejunal mucosa on day 21 and 42. The WB supplementation enhanced the α-diversity of cecal microbiota, as evidenced by the increased Shannon index (P < 0.05). At the phylum level, the phylum Firmicutes was enriched (P < 0.05) in WB. At the genus level, the WB supplementation enriched (P < 0.05) Lachnoclostridium and Butyricicoccus. The WB supplementation increased (P < 0.05) cecal total short chain fatty acids concentrations on day 21 and 42, and butyric acid concentrations on day 42 compared with CON. Collectively, supplementation of 3% WB could promote growth by improving intestinal immunity, barrier function, and microbial composition in broilers. Thus, WB may have a role in replacing antibiotics for improved growth performance and intestinal health in broilers.


Assuntos
Antibacterianos , Galinhas , Fibras na Dieta , Microbioma Gastrointestinal , Intestinos , Ração Animal/análise , Animais , Antibacterianos/farmacologia , Galinhas/crescimento & desenvolvimento , Galinhas/imunologia , Dieta/veterinária , Fibras na Dieta/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Masculino
10.
Poult Sci ; 99(9): 4488-4495, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32867992

RESUMO

Plant extracts have been proved as natural antioxidants resources as well as alternative feed additives in livestock and poultry species. Chestnut wood extract (CWE) as a source of hydrolysable tannic acid was used to evaluate the growth performance, nutrient retention, meat quality, antioxidant status, and immune function of broilers. A total of 168, day-old Arbor Acre male broilers (weight 46.59 ± 0.44 g) were randomly divided to 3 treatments, 7 replicate pens per treatment, 8 broilers per pen. The treatments contain a control diet, CON (corn-soybean meal basal diet); an antibiotic diet, CTC (basal diet + 75 mg/kg chlortetracycline); and chestnut wood extract diet, CWE (basal diet + 1,000 mg/kg chestnut tannins). At the finisher phase, final body weight was higher (P < 0.05) in CWE supplemented diet than in CON. Average daily body weight gain was higher (P < 0.05) and feed gain ratio was lower (P < 0.05) in broilers fed CWE than in those fed CON at the finisher phase. Crude protein digestibility was higher (P < 0.05) in broilers offered CWE than that in broilers fed CON and CTC diets. Breast muscle pH value at 24 h (pH24 h) was higher (P < 0.05) in broilers fed CWE than that in those fed CON and CTC diets. The bursa weight was higher (P < 0.05) in broilers offered CWE than that in those fed CON and CTC. Total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) values were higher (P < 0.05) in both breast muscle and thigh muscle of broilers offered CWE supplemented diet than those in broilers fed CON and CTC diets. Similarly, broilers offered with CWE diets showed higher (P < 0.05) T-AOC, GSH-PX, and SOD value in serum than those fed CON and CTC diets. Serum concentration of IgG was higher (P < 0.05) in broilers offered with CWE diets than that in those fed CON and CTC diets. Total cholesterol, low-density lipoprotein cholesterol, and urea-N concentration were lower (P < 0.05) in broilers offered CWE diet than those in broilers fed CON and CTC diets. It was recommended to supply CWE at the 1,000 mg/kg level for improving antioxidant status, cholesterol metabolism, and growth performance without affecting normal meat quality in broilers.


Assuntos
Aesculus , Antioxidantes , Galinhas , Suplementos Nutricionais , Imunidade , Carne , Extratos Vegetais , Aesculus/química , Fenômenos Fisiológicos da Nutrição Animal , Animais , Galinhas/imunologia , Colesterol/metabolismo , Dieta/veterinária , Imunidade/efeitos dos fármacos , Masculino , Carne/normas , Extratos Vegetais/farmacologia , Madeira/química
11.
Neoplasma ; 67(5): 1032-1041, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32453598

RESUMO

Nasopharyngeal cancer (NPC) is a type of head and neck cancer with a high rate of metastasis. Circular RNAs (circRNAs) were reported to be related to the development of human cancers. This research aimed to investigate the functional mechanism of circRNA circ_0000615 in NPC. The gene expression was examined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was employed to assess cell proliferation ability. Transwell assay was used to measure cell migratory and invasive abilities. Furthermore, the interaction between miR-338-3p and circ_0000615 or fibroblast growth factor 2 (FGF2) was predicted by starBase v.2.0 and then confirmed by the dual-luciferase reporter assay. Besides, the mouse xenograft experiment was carried out to explore the effect of circ_0000615 on tumor growth in vivo. We detected increased levels of circ_0000615 and FGF2, along with a decreased level of miR-338-3p in NPC tissues and cells. Circ_0000615 knockdown suppressed the proliferation, migration, invasion, and EMT of NPC cells. Interestingly, circ_0000615 interacted with miR-338-3p, and miR-338-3p targeted FGF2. Circ_0000615 inhibited miR-338-3p expression to upregulate the FGF2 level. Furthermore, both miR-338-3p depletion and FGF2 overexpression weakened the effect of circ_0000615 knockdown on NPC cell progression. Besides, circ_0000615 knockdown repressed tumor growth in vivo. In conclusion, our findings demonstrated that circ_0000615 knockdown suppressed the growth of NPC cells via modulating miR-338-3p/FGF2 axis, providing a theoretical basis for the treatment of NPC.


Assuntos
Fator 2 de Crescimento de Fibroblastos/genética , MicroRNAs/genética , Neoplasias Nasofaríngeas , RNA Circular/genética , Animais , Linhagem Celular Tumoral , Movimento Celular , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia
12.
Eur Rev Med Pharmacol Sci ; 23(4): 1528-1535, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30840275

RESUMO

OBJECTIVE: In order to investigate the role of the zinc finger E-box-binding homeobox 1 (ZEB1) expression in the incidence of non-small cell lung cancer (NSCLC), the effects of the ZEB1 expression on the pathogenesis and prognosis of NSCLC were investigated. PATIENTS AND METHODS: Correlations of the expression of ZEB1 in 88 clinical patients with NSCLC with clinicopathological features were determined. The patients were followed up for 60 months to study the correlation between the ZEB1 expression and the prognosis of NSCLC patients. To further explore the role of the ZEB1 expression in the incidence of NSCLC, the expressions of ZEB1 and E-cadherin in three NSCLC cell lines (A549, NCI-H1299 and NCI-H1975) and human normal lung epithelial BESA-2B cell line were measured, and the cell invasion ability was detected. The role of ZEB1 in NSCLC cell invasion was verified through the knockdown of ZEB1 by the short hairpin ribonucleic acids (shRNAs). In addition, its effects on the proliferation and apoptosis of NSCLC cells were confirmed by the overexpression of ZEB1. RESULTS: The expression of ZEB1 in NSCLC tissues was remarkably higher than that in normal tissues, and the expression level of ZEB1 was significantly related to the cancer stage and tumor size. The lower the expression of ZEB1 was, the higher the overall survival rate and the longer the survival time would be. The expression of ZEB1 was negatively correlated with that of E-cadherin in cell lines, and ZEB1-shRNAs markedly reduced the invasion ability of NSCLC cells. The overexpression of ZEB1 resulted in an increase in the proliferation activity and a significant decrease in the apoptosis of A549 cells. CONCLUSIONS: The expression of ZEB1 is closely related to the incidence and prognosis of NSCLC. Increased expression of ZEB1 is helpful for promoting the invasion of NSCLC and enhancing the proliferation activity of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Apoptose , Caderinas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Linhagem Celular Tumoral , Movimento Celular , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/antagonistas & inibidores , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética
13.
Zhonghua Yi Xue Za Zhi ; 97(35): 2770-2774, 2017 Sep 19.
Artigo em Chinês | MEDLINE | ID: mdl-28954337

RESUMO

Objectives: To investigate the clinical features, diagnosis and treatment of antibody mediated paraneoplastic neurological syndrome associated with thymoma. Methods: From 2012 to 2017, the paraneoplastic antibody and neuron antibody were tested from both blood and cerebrospinal fluid (CSF) in consecutive patients clinically suspected with neurological paraneoplastic syndromes/unknown encephalitis in Peking Union Medical College Hospital.The clinical data, lab results, electrophysiological examinations, imaging features, treatment and clinical prognosis were collected.In this study, the patients who met the diagnostic criteria of both thymoma and neurological paraneoplastic syndrome were retrospectively analyzed.The functional severity was assessed by modified Rankin score(mRS). Results: Six patients (4 female and 2 male) were included for the analysis.Of them, 4 patients presented with limbic encephalitis, 1 with peripheral neuropathy accompanying with myasthenia gravis and 1 with spinal and cerebella degeneration.Three patients were in severe condition (mRS=5). Positive α-amino-3-hydroxy-5-methyl-4-iso xazolepropionic acid receptor, antibody (AMPAR) was identified in 3 patients(2 in blood and CSF, 1 in blood), CV2 plus acetylcholine receptor antibody (ACH-Ab) positive in blood was seen in 1 patient and positive N-methyl-D-aspartate receptor (NMDAR) in blood and CSF in 1 patient. Brain MRI showed abnormalities in 2 patients.The CT scan revealed thymoma in all 6 patients.All patients received intravenous immunogloblin (IVIG) and/or glucocorticoid immediately after diagnosis.Furthermore, thymectomy was performed in 5 patients. All the patients were remarkably improved with mRS 0-1 at discharge.Five patients were clinical stable within follow-up of 1-2.5 years.However, one patient who refused thymectomy experienced several clinical recurrencs. Conclusions: Antibodies mediated paraneoplastic neurological syndrome/autoimmune encephalitis can occur in patients with thymoma with typical characteristics. The correlated antibody test and chest CT might be important in patients clinically suspected with neurological paraneoplastic syndrome or encephalitis with unknown reason. Surgical thymectomy combining with active immunological treatment may play a role in the favorable prognosis, even in those clinical severe patients.


Assuntos
Síndromes Paraneoplásicas , Timoma , Neoplasias do Timo , Autoanticorpos , Feminino , Humanos , Masculino , Estudos Retrospectivos , Timectomia
15.
Zhonghua Zhong Liu Za Zhi ; 38(9): 660-6, 2016 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-27647397

RESUMO

OBJECTIVE: To study the intratumor heterogeneity of esophageal squamous cell carcinoma (ESCC). METHODS: We used whole-exome sequencing and array-based comparative genomic hybridization to profile mutations and changes in copy number from 11 regions within 2 cases of ESCC and from the metastatic lymph nodes. RESULTS: The numbers of somatic single nuclear polymorphisms (SNPs) in 4 regions within the tumors in case 1 and case 2 were 93±17 and 124±28, respectively. The majority of SNPs were non synonymous mutations, synonymous mutations, nonsense mutations and splicing junction mutations. The average indels in the 4 tumor regions of case 1 and case 2 were 40±6 and 51±3, respectively. These small indels mainly occurred in exonic (frame-shift and non-frame-shift), untranslational regions of genes and splicing junction regions. All regions from a tumor exhibitedo bvious heterogeneity, and mutational similarity of all four regions within a tumor was less than 25%. Furthermore, gene copy number alteration (gain or loss) varied among multiple regions of a tumor, and the similarity of gene copy number was less than 20%. Phylogenetic analysis of the somatic mutation frequency suggests that multiple, genomic heterogeneous clones co-exist within a primary ESCC, and metastatic subclones may evolve from the primary non-metastatic parental clone. These results indicated that a single-region sampling can not reflect the architecture of the genomic landscape of mutations in ESCC tumors. CONCLUSIONS: Sequence analysis of whole genome exon in multiple regions can provide strong evidence for genomic heterogeneity in esophageal squamous cell carcinoma.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Hibridização Genômica Comparativa , Carcinoma de Células Escamosas do Esôfago , Dosagem de Genes , Genômica , Humanos , Linfonodos , Metástase Linfática , Mutação , Filogenia
16.
Blood Cancer J ; 6(7): e442, 2016 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-27391574

RESUMO

Clinical outcome and mutations of 96 core-binding factor acute myeloid leukemia (AML) patients 18-60 years old were examined. Complete remission (CR) after induction was 94.6%. There was no significant difference in CR, leukemia-free-survival (LFS) and overall survival (OS) between t(8;21) (N=67) and inv(16) patients (N=29). Univariate analysis showed hematopoietic stem cell transplantation at CR1 as the only clinical parameter associated with superior LFS. Next-generation sequencing based on a myeloid gene panel was performed in 72 patients. Mutations in genes involved in cell signaling were associated with inferior LFS and OS, whereas those in genes involved in DNA methylation were associated with inferior LFS. KIT activation loop (AL) mutations occurred in 25 patients, and were associated with inferior LFS (P=0.003) and OS (P=0.001). TET2 mutations occurred in 8 patients, and were associated with significantly shorter LFS (P=0.015) but not OS. Patients negative for KIT-AL and TET2 mutations (N=41) had significantly better LFS (P<0.001) and OS (P=0.012) than those positive for both or either mutation. Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age ⩾40 years and marrow blast ⩾70% were associated with inferior OS. These observations provide new insights that may guide better treatment for this AML subtype.


Assuntos
Fatores de Ligação ao Core/genética , Fatores de Ligação ao Core/metabolismo , Proteínas de Ligação a DNA/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Mutação , Proteínas Proto-Oncogênicas c-kit/metabolismo , Proteínas Proto-Oncogênicas/genética , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Metilação de DNA , Análise Mutacional de DNA , Proteínas de Ligação a DNA/metabolismo , Dioxigenases , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Transdução de Sinais , Análise de Sobrevida , Translocação Genética , Transplante Homólogo , Adulto Jovem
17.
Clin Radiol ; 71(9): 837-43, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27302496

RESUMO

AIM: To review the fetal magnetic resonance imaging (MRI) features of pyriform sinus fistula (PSF) and to compare them with the postnatal clinical and surgical findings. The relevant medical literature is also discussed. MATERIALS AND METHODS: The location, shape, signal, effects of adjacent structures and in utero changes detected on fetal MRI were reviewed in three cases of PSF. The patient's respiratory status at birth, the application of ex utero intrapartum therapy (EXIT), infectious complications in the neonatal period, and the surgical and pathological findings were also reviewed and discussed. The study consisted of three pregnant women between 18 and 38 years of age, each with a single fetus. Fetal MRI was performed at 26 and 38 weeks of gestation in case 1, at 34 weeks of gestation in case 2, and at 34 and 38 weeks of gestation in case 3. Postnatal clinical follow-up extended from 9 months to 3 years. RESULTS: All lesions were well-circumscribed unilobular cysts with slightly thickened walls at the neck area. Case 1 was irregular in shape, and the other two cases were oval and extended longitudinally along the neck. The fluid contents showed signals consistent with amniotic fluid. Close contact with the thyroid gland was demonstrated to be a fairly characteristic feature that could be recognised on fetal MRI. The in utero follow-up detected slight changes in the signal, wall characteristics, contour, and airway deviation. Case 1 was bilaterally affected, causing it to be initially mistaken as macro-cystic lymphangioma. The diagnosis was corrected with the aid of postnatal imaging; however, a prenatal diagnosis was correctly made in cases 2 and 3. Airway obstruction was not observed in any of the three cases, and thus, EXIT was not applied. The fetal MRI findings were in good agreement with the postnatal clinical and surgical findings. In addition to the higher spatial delineation provided by fetal MRI, as described in the literature, the observation of close contact with the thyroid gland and a flattened deformity of the thyroid gland are other characteristic features. CONCLUSION: Fetal MRI is useful for displaying characteristics of PSF that can enable an accurate prenatal diagnosis.


Assuntos
Fístula/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Doenças Faríngeas/diagnóstico por imagem , Diagnóstico Pré-Natal/métodos , Seio Piriforme/anormalidades , Seio Piriforme/diagnóstico por imagem , Adolescente , Adulto , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Posicionamento do Paciente/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
18.
Curr Res Transl Med ; 64(1): 21-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27140596

RESUMO

BACKGROUND: Myocarditis, characterized by myocyte necrosis, fibrosis, and degeneration with mononuclear cell infiltration, always causes heart failure in patients. Phosphoinositide 3-kinase (PI3K) is a pivotal kinase known to regulate inflammatory responses in cardiac diseases. Although previous research has suggested that PI3K was involved in cardiac diseases such as myocardial infarction, it is still unclear whether the inhibition of PI3K is essential for the treatment of myosin-induced myocarditis. The aim of this study was to explore whether pharmacological blockade of PI3K is able to protect mice against experimental autoimmune myocarditis (EAM). MATERIALS AND METHODS: We used the cardiac myosin-induced murine EAM model to investigate the therapeutic effect of PI3K inhibitor LY294002 on autoimmune myocarditis in mice. RESULTS: LY294002 significantly alleviated EAM injury in mice, as indicated by the reduction of cardiac necrosis, inflammatory infiltrates, and CD3(+) T cells. LY294002 also decreased the expression of p-Akt upon cardiac myosin treatment in the cardiac tissue of the mice. In the present study, LY294002 resulted in a moderate reduction in absolute CD4(+) cell numbers and a significant decrease in the absolute numbers of CD8(+) cells. Consequently, LY294002 increased the CD4(+)/CD8(+) ratio compared with peptide treatment alone. CONCLUSION: This report provides evidence that PI3K inhibitor LY294002 has potent effects against cardiac injury caused by EAM, suggesting that it has therapeutic value for the treatment of myocarditis.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Cromonas/uso terapêutico , Morfolinas/uso terapêutico , Miocardite/tratamento farmacológico , Inibidores de Fosfoinositídeo-3 Quinase , Animais , Doenças Autoimunes/enzimologia , Doenças Autoimunes/etiologia , Doenças Autoimunes/patologia , Cromonas/farmacologia , Citocinas/sangue , Avaliação Pré-Clínica de Medicamentos , Feminino , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Morfolinas/farmacologia , Miocardite/enzimologia , Miocardite/etiologia , Miocardite/patologia , Miocárdio/imunologia , Miocárdio/patologia , Cadeias Pesadas de Miosina/imunologia , Cadeias Pesadas de Miosina/toxicidade , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/toxicidade , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas Proto-Oncogênicas c-akt/metabolismo , Miosinas Ventriculares/imunologia , Miosinas Ventriculares/toxicidade
20.
Neurology ; 75(24): 2185-9, 2010 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-21172841

RESUMO

BACKGROUND: The association between protein S deficiency (PSD) and ischemic stroke is controversial and warrants further investigation. METHODS: We conducted a genotype and MRI correlation study in a Chinese family in which hereditary PSD cosegregated with premature ischemic strokes. Six out of 11 family members inherited PSD type III in an autosomal dominant manner. RESULTS: Among all PSD members, a novel missense mutation 1063C→T in exon 10 of protein S alpha (PROS1) was identified, which encoded a substitution of arginine to cysteine at position 355 (R355C) in the first globular domain of laminin A of protein S. Wild-type PROS1 sequences were retained in non-PSD members. MRI detected deep white matter infarctions predominantly distributed in the borderzone regions. The infarct topography was homogeneous in all adult mutant carriers. By contrast, cerebral infarction was absent in nonmutant carriers. Extensive investigation in the family did not reveal any confounding stroke risk. Haplotype analysis with high-density single nucleotide polymorphism markers revealed a 6.1-Mb minimally rearranged region (rs12494685 to rs1598240) in 3q11.2, lod = 3.0. Among the 7 annotated genes in this region, PROS1 is known to be associated with thrombotic disorders. MRI screening in an additional 10 PSD families without R355C showed no cerebral infarction. CONCLUSIONS: PROS1 R355C mutation cosegregated with PSD type III and premature white matter infarctions in the index family. The findings substantiate an association between PSD and stroke. Study of the mechanism underlying this association may improve our understanding of premature cryptogenic white matter infarction.


Assuntos
Encéfalo/patologia , Infarto Cerebral/genética , Infarto Cerebral/patologia , Mutação de Sentido Incorreto , Deficiência de Proteína S/complicações , Proteína S/genética , Adolescente , Adulto , Idoso , Arginina , Encéfalo/irrigação sanguínea , Criança , Cisteína , Feminino , Predisposição Genética para Doença , Haplótipos , Hong Kong , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Linhagem , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Adulto Jovem
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