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1.
World J Gastrointest Surg ; 15(8): 1712-1718, 2023 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-37701702

RESUMO

BACKGROUND: There are many risk factors for severe acute pancreatitis (SAP) complicated with acute gastrointestinal injury (AGI), but few reports on the interaction between these risk factors. AIM: To analyze the risk factors for SAP complicated with AGI and their interactive effects. METHODS: We selected 168 SAP patients admitted to our hospital between December 2019 and June 2022. They were divided into AGI group and non-AGI group according to whether AGI was present. Demographic data and laboratory test data were compared between the two groups. The risk factors for SAP with concomitant AGI were analyzed using multifactorial logistic regression, and an analysis of the interaction of the risk factors was performed. RESULTS: The percentage of patients with multiple organ dysfunction syndrome, acute physiological and chronic health scoring system II (APACHE II) score, white blood cell count and creatinine (CRE) level was higher in the AGI group than in the non-AGI group. There was a statistically significant difference between the two groups (P < 0.05). Logistic regression analysis indicated that an APACHE II score > 15 and CRE > 100 µmol/L were risk factors for SAP complicating AGI. The interaction index of APACHE II score and CRE level was 3.123. CONCLUSION: An APACHE II score > 15 and CRE level > 100 µmol/L are independent risk factors for SAP complicated with AGI, and there is a positive interaction between them.

2.
World J Gastroenterol ; 28(12): 1257-1271, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35431509

RESUMO

BACKGROUND: Choledocholithiasis is a severe disorder that affects a significant portion of the world's population. Treatment using endoscopic sphincterotomy (EST) has become widespread; however, recurrence post-EST is relatively common. The bile microbiome has a profound influence on the recurrence of choledocholithiasis in patients after EST; however, the key pathogens and their functions in the biliary tract remain unclear. AIM: To investigate the biliary microbial characteristics of patients with recurrent choledocholithiasis post-EST, using next-generation sequencing. METHODS: This cohort study included 43 patients, who presented with choledocholithiasis at the Guangdong Second Provincial General Hospital between May and June 2020. The patients had undergone EST or endoscopic papillary balloon dilation and were followed up for over a year. They were divided into either the stable or recurrent groups. We collected bile samples and extracted microbial DNA for analysis through next-generation sequencing. Resulting sequences were analyzed for core microbiome and statistical differences between the diagnosis groups; they were examined using the Kyoto Encyclopedia of Genes and Genomes pathway hierarchy level using analysis of variance. Correlation between the key genera and metabolic pathways in bile, were analyzed using Pearson's correlation test. RESULTS: The results revealed distinct clustering of biliary microbiota in recurrent choledocholithiasis. Higher relative abundances (RAs) of Fusobacterium and Neisseria (56.61% ± 14.81% vs 3.47% ± 1.10%, 8.95% ± 3.42% vs 0.69% ± 0.32%, respectively) and the absence of Lactobacillus were observed in the bile of patients with recurrent disease, compared to that in stable patients. Construction of a microbiological co-occurrence network revealed a mutual relationship among Fusobacterium, Neisseria, and Leptotrichia, and an antagonistic relationship among Lactobacillales, Fusobacteriales, and Clostridiales. Functional prediction of biliary microbiome revealed that the loss of transcription and metabolic abilities may lead to recurrent choledocholithiasis. Furthermore, the prediction model based on the RA of Lactobacillales in the bile was effective in identifying the risk of recurrent choledocholithiasis (P = 0.03). CONCLUSION: We demonstrated differences in the bile microbiome of patients with recurrent choledocholithiasis compared to that in patients with stable disease, thereby adding to the current knowledge on its microbiologic etiology.


Assuntos
Coledocolitíase , Esfinterotomia Endoscópica , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Coledocolitíase/cirurgia , Estudos de Coortes , Humanos , Fatores de Risco , Esfinterotomia Endoscópica/efeitos adversos , Esfinterotomia Endoscópica/métodos , Resultado do Tratamento
3.
Front Oncol ; 11: 624413, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763360

RESUMO

BACKGROUND: The impact of lymph nodes (LNs) removed on the survivals of patients with stage III gastric cancer, especially on that of those who undergo the adjuvant chemotherapy as a compensation for a possibly insufficient lymphadenectomy, is still unclear. METHODS: Consecutive patients (n = 488) with stage III gastric cancer under R0 curative resection followed by adjuvant chemotherapy were analyzed. The overall survival (OS) was compared between patients with insufficient LNs removed (ILNr, <16 LNs) and sufficient LNs removed (SLNr, ≥16 LNs). Performance of the prediction systems was evaluated using the Likelihood ratio χ2 test, Akaike information criterion (AIC), Harrell's concordance index (C-index), and area under the receiver operating characteristic curves (AUC). RESULTS: The OS of patients were significantly longer in those with SLNr relative to those with ILNr (for stage IIIA, 68.2 vs. 43.2 months, P = 0.042; for stage IIIB, 43.7 vs. 24.9 months, P < 0.001; for stage IIIC, 23.9 vs. 8.3 months, P < 0.001; and for total stage III, 37.7 vs. 21.7 months, P < 0.001). However, the OS were similar between stage IIIA patients with ILNr and stage IIIB patients with SLNr (P = 0.928), between IIIB patients with ILNr and IIIC patients with SLNr (P = 0.962), and IIIC patients with ILNr and stage IV (P = 0.668), respectively. A substage increase in the AJCC classification system, from IIIA to IIIB, from IIIB to IIIC, and from IIIC to IV in patients with ILNr, enhanced the accuracy of prognostic prediction in patients with stage III gastric cancer compared to the current TNM system (Likelihood ratio χ2, 188.6 vs. 184.8; AIC, 4336.4 vs. 4340.6; C-index, 0.695 vs. 0.679, P = 0.002). The ROC curves revealed that the performance of prognostic prediction was better in the new prediction system (AUC = 0.699) compared with the current TNM system (AUC = 0.676). CONCLUSIONS: ILNr (LNs <16) impairs the long-term outcomes of stage III gastric cancer underwent adjuvant chemotherapy. The status of LNs removal adds values to the current TNM system in prognostic prediction of stage III gastric cancer.

4.
Front Plant Sci ; 11: 1276, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973836

RESUMO

Stylosanthes species are economically important tropical and subtropical forage legumes which are generally vulnerable to chilling and frost. Fine-stem stylo (S. guianensis var. intermedia) has the most superior cold tolerance among all stylo species. A REVEILLE (RVE) gene, SgRVE6, was cloned from fine-stem stylo. Bioinformatic analysis suggests that SgRVE6 encodes a transcription factor of 292 amino acid residues, which belongs to the LATE ELONGATED HYPOCOTYL/CIRCADIAN CLOCK ASSOCIATED 1-LIKE (LCL) subgroup of RVE family and contains a SHAQKYF-class MYB domain and a LCL domain. SgRVE6 is universally expressed in root, stem and leaf tissues of fine-stem stylo and is rapidly up-regulated in all tested tissues under cold stress. Over-expressing SgRVE6 affects expression of 21 circadian clock genes, up-regulates expression of 6 nucleotide binding domain leucine-rich repeats (NB-LRR) encoding genes associated with tobacco cold tolerance, improves physiological responses to low temperature, and endows the transgenic tobaccos with higher tolerance to cold stress. This is the first time a study investigates the biological function of RVE6 in cold responses of plant species.

5.
J Gastrointest Surg ; 23(7): 1474-1484, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30617772

RESUMO

BACKGROUND: Rectal cancers have long been treated as a single-entity disease; however, whether the prognosis of high rectal cancer (inferior margin located 10.1 to 15.0 cm from the anal verge) differs from that of mid/low rectal cancer (0 to 10.0 cm) remains disputed. METHODS: Patients with stages I-III rectal adenocarcinomas undergoing curative-intent surgery were enrolled between 2007 and 2013 in this retrospective analysis. Exclusion criteria were neoadjuvant therapy or concurrent cancers. Propensity score matching and Cox regression analysis were performed to compare a 5-year overall and cancer-specific survival between patients with high and mid/low rectal cancer. RESULTS: Of 613 patients who met the inclusion criteria, 199 (32.5%) and 414 (67.5%) had high and mid/low rectal cancer, respectively. After propensity score matching (187 cases for each group), the high group showed a better overall survival (70.9 vs. 56.9%, p = 0.042) and cancer-specific survival (77.4 vs. 60.3%, p = 0.028) at 5 years compared with the mid/low group with stage III disease. However, high rectal cancer did not demonstrate prognostic superiority in stages I-II disease. Multivariate analysis identified high tumor location as an independent prognostic factor for cancer-specific survival (hazards ratio = 0.422, 95% confidence interval 0.226-0.786, p = 0.007) and overall survival (hazards ratio = 0.613, 95% confidence interval 0.379-0.991, p = 0.046). CONCLUSIONS: Patients with stage III high rectal adenocarcinoma demonstrated better overall and cancer-specific survival than those with mid/low type, and tumor location was an independent prognostic factor for patients with rectal carcinomas.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Reto/patologia , Adenocarcinoma/secundário , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida
6.
Life Sci ; 208: 55-63, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29990485

RESUMO

AIMS: To establish multiparametric radiomics of rectal tumor for the preoperative prediction of lymph node (LN) metastasis. MATERIALS AND METHODS: This prospective study consisted of 115 consecutive patients with rectal carcinoma between April 2015 and April 2017. The multiparametric radiomics scores were extracted from the endorectal ultrasound (ERUS), computed tomography (CT) and shear-wave elastography (SWE) features of the rectal tumor, LN, and peripheral tissues. The three radiomics scores were generated. Further validation as an independent predictor was performed using multivariate logistic regression together with clinical data, and a nomogram was subsequently developed. The predictive performance of the multiparametric radiomics nomogram was compared with that of conventional radiomics. KEY FINDINGS: All three scores (ERUS, CT, and SWE) were significantly higher in patients with LN metastasis than in patients with negative LN metastasis (all P < 0.05) in both training and validation set. Multivariate analysis indicated that CT and SWE scores were independent risk variables (odds ratio, OR = 6.764 and 5.482, respectively). In validation cohort, the multiparametric radiomics nomogram showed the highest predictive accuracy for LN metastasis, with a concordance index (C-index) of 0.857 compared with the conventional radiomics nomogram (C-index, 0.703, P = 0.100), resulting in a significantly improved net reclassification index (NRI) (P < 0.05) and integrated discriminatory improvement (IDI) (P = 0.002). Decision curve analysis showed that the multiparametric radiomics nomogram had a higher overall net benefit. SIGNIFICANCE: Multiparametric radiomics of rectal cancer, which captures blood supply and stiffness phenotypes, is a useful tool for predicting LN metastasis preoperatively and has marked discrimination accuracy compared to conventional radiomics.


Assuntos
Adenocarcinoma/secundário , Técnicas de Imagem por Elasticidade/métodos , Endossonografia/métodos , Imagem Multimodal/métodos , Nomogramas , Neoplasias Retais/patologia , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Neoplasias Retais/diagnóstico por imagem
7.
World J Gastroenterol ; 23(34): 6261-6272, 2017 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-28974892

RESUMO

AIM: To investigate the clinical significance of preoperative systemic immune-inflammation index (SII) in patients with colorectal cancer (CRC). METHODS: A retrospective analysis of 1383 cases with CRC was performed following radical surgery. SII was calculated with the formula SII = (P × N)/L, where P, N, and L refer to peripheral platelet, neutrophil, and lymphocyte counts, respectively. The clinicopathological features and follow-up data were evaluated to compare SII with other systemic inflammation-based prognostic indices such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in patients with CRC. RESULTS: The optimal cut-off point for SII was defined as 340. The overall survival (OS) and disease-free survival (DFS) were better in patients with low NLR, PLR, and SII (P < 0.05). The SII was an independent predictor of OS and DFS in multivariate analysis. The area under the receiver-operating characteristics (ROC) curve for SII (0.707) was larger than those for NLR (0.602) and PLR (0.566). In contrast to NLR and PLR, SII could effectively discriminate between the TNM subgroups. CONCLUSION: SII is a more powerful tool for predicting survival outcome in patients with CRC. It might assist the identification of high-risk patients among patients with the same TNM stage.


Assuntos
Plaquetas/imunologia , Neoplasias Colorretais/sangue , Inflamação/sangue , Linfócitos/imunologia , Neutrófilos/imunologia , Quimioterapia Adjuvante , Colo/patologia , Colo/cirurgia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Intervalo Livre de Doença , Feminino , Humanos , Inflamação/imunologia , Inflamação/mortalidade , Inflamação/terapia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Contagem de Plaquetas , Período Pré-Operatório , Prognóstico , Reto/patologia , Reto/cirurgia , Estudos Retrospectivos , Medição de Risco/métodos
8.
J Biol Chem ; 292(34): 14165-14175, 2017 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-28687631

RESUMO

Circadian clock and Smad2/3/4-mediated Nodal signaling regulate multiple physiological and pathological processes. However, it remains unknown whether Clock directly cross-talks with Nodal signaling and how this would regulate embryonic development. Here we show that Clock1a coordinated mesoderm development and primitive hematopoiesis in zebrafish embryos by directly up-regulating Nodal-Smad3 signaling. We found that Clock1a is expressed both maternally and zygotically throughout early zebrafish development. We also noted that Clock1a alterations produce embryonic defects with shortened body length, lack of the ventral tail fin, or partial defect of the eyes. Clock1a regulates the expression of the mesodermal markers ntl, gsc, and eve1 and of the hematopoietic markers scl, lmo2, and fli1a Biochemical analyses revealed that Clock1a stimulates Nodal signaling by increasing expression of Smad2/3/4. Mechanistically, Clock1a activates the smad3a promoter via its E-box1 element (CAGATG). Taken together, these findings provide mechanistic insight into the role of Clock1a in the regulation of mesoderm development and primitive hematopoiesis via modulation of Nodal-Smad3 signaling and indicate that Smad3a is directly controlled by the circadian clock in zebrafish.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Desenvolvimento Embrionário , Mesoderma/metabolismo , Proteína Nodal/agonistas , Transdução de Sinais , Proteína Smad3/agonistas , Proteínas de Peixe-Zebra/agonistas , Peixe-Zebra , Animais , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Embrião não Mamífero/anormalidades , Embrião não Mamífero/citologia , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento , Células HEK293 , Hematopoese/efeitos dos fármacos , Humanos , Hibridização In Situ , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Mesoderma/anormalidades , Mesoderma/citologia , Mesoderma/efeitos dos fármacos , Microinjeções , Microscopia de Fluorescência , Morfolinos/farmacologia , Mutação , Proteína Nodal/genética , Proteína Nodal/metabolismo , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Elementos de Resposta/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteína Smad3/antagonistas & inibidores , Proteína Smad3/genética , Proteína Smad3/metabolismo , Proteínas de Peixe-Zebra/antagonistas & inibidores , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
9.
Cancer Cell Int ; 17: 64, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28615992

RESUMO

BACKGROUND: Recent studies have verified that long noncoding RNAs (lncRNAs) involved in many biological functions and play crucial roles in human cancers progression, the study aimed to detect the association between long non-coding RNA HOXA11-AS and epithelial-mesenchymal transition (EMT) process in non-small cell lung cancer (NSCLC). METHODS: The lncRNA HOXA11-AS expression levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) assays in 78 paired of tumor tissue and adjacent normal tissue samples in NSCLC patients. Kaplan-Meier survival curves and log-rank test was used to examine the association between lncRNA HOXA11-AS expression and the over survival time in NSCLC patients. Transwell invasion assay was performed to detect the cell invasion ability. QRT-PCR and western-blot analysis detected the mRNA and protein expression of EMT related transcription factors ZEB1/ZEB2, Snail1/2 and EMT marker E-cadherin and N-cadherin in NSCLC cells. RIP and Chromatin immunoprecipitation assays were performed to analyze the association between lncRNA HOXA11-AS and miR-200b expression in NSCLC cells. RESULTS: The lncRNA HOXA11-AS expression levels were significantly higher in NSCLC tissues compared with adjacent normal tissues and higher HOXA11-AS expression levels had a poor prognosis in NSCLC patients. Furthermore, knockdown of lncRNA HOXA11-AS in A549 and H1299 cells dramatically inhibited cell invasive abilities. Besides, the transcription levels and protein levels of EMT related transcription factors ZEB1/ZEB2, Snail1/2, and EMT maker N-cadherin were down-regulated after lncRNA HOXA11-AS was knocked down, but the mRNA and protein expression levels of EMT maker E-cadherin was increasing in A549 and H1299 cells. The mechanistic findings showed demonstrated that HOXA11-AS interacted with EZH2 and DNMT1 and recruited them to the miR-200b promoter regions to repress miR-200b expression in NSCLC cells, which promoted cell EMT in NSCLC. CONCLUSIONS: Our results showed that up-regulation of lncRNA HOXA11-AS predicted a poor prognosis and lncRNA HOXA11-AS promoted cell epithelial-mesenchymal transition (EMT) by inhibiting miR-200b expression in NSCLC.

10.
Radiology ; 285(1): 279-292, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28640694

RESUMO

Purpose To compare the value of endorectal ultrasonography (US) with shear-wave elastography (SWE) in staging rectal tumors before surgery. Materials and Methods This prospective study was approved by the institutional review board and written informed consent was obtained. In a pilot cohort from April 2015 to January 2016, 70 patients with rectal adenocarcinomas and/or adenomas confirmed with histopathologic examination underwent both endorectal US and SWE. Tumor stiffness and three regions of reference backgrounds, as well as tumor stiffness ratios (SRs) versus these backgrounds, were analyzed. The optimal staging feature was selected by using receiver operating characteristic analysis, and the concordance rate with pathologic stage was analyzed and compared with endorectal US. The results were validated in an independent cohort of 30 patients from February 2016 to July 2016. Results In the pilot study, from rectal adenoma to stage T3 cancers, the tumor stiffness, stiffness of peritumoral fat, tumor SR versus distant perirectal fat, and tumor SR versus normal rectal wall were significantly increased (all P < .05, correlation coefficients between SWE features and pathologic T stages were 0.589-0.853). Receiver operating characteristic analysis of tumor staging demonstrated that tumor stiffness was the optimal feature with the highest area under the receiver operating characteristic curve (AUC = 0.991-1.000). The cutoff values of stage T1, T2, and T3 cancers were 26.9 kPa, 70.3 kPa, and 112.0 kPa, respectively. For SWE, the diagnostic concordance rate with pathologic stage (95.7%, weighted κ = 0.962) was higher than that of endorectal US (75.7%, weighted κ = 0.756). In the validation cohort, similar findings were revealed for diagnostic concordance rate (93.3% vs 76.7%; weighted κ = 0.927 vs 0.651) and diagnostic performance of tumor staging (AUC = 0.950-1.000 vs 0.700-0.833). Conclusion By using the feature of tumor stiffness at SWE, the accuracy of preoperative staging for rectal tumors was improved compared with endorectal US in the pilot study, but was not significantly different in the validation cohort, potentially due to small sample size. © RSNA, 2017 Online supplemental material is available for this article.


Assuntos
Técnicas de Imagem por Elasticidade , Neoplasias Retais/diagnóstico por imagem , Ultrassonografia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas de Imagem por Elasticidade/métodos , Técnicas de Imagem por Elasticidade/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Curva ROC , Neoplasias Retais/cirurgia , Reprodutibilidade dos Testes , Ultrassonografia/métodos , Ultrassonografia/estatística & dados numéricos
11.
J Huazhong Univ Sci Technolog Med Sci ; 37(2): 243-247, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28397051

RESUMO

Soluble receptor for advanced glycation end products (sRAGE) can decoy the toxic AGEs and is considered to be a protective factor. This study aimed to evaluate the correlation between intrafollicular sRAGE levels and clinical outcomes in infertile women of young or advanced maternal age (AMA) undergoing in vitro fertilization (IVF). A total of 62 young women and 62 AMA women who would undergo IVF were included in this prospective study. The intrafollicular sRAGE concentration was measured to determine its association with the number of retrieved oocytes, fertilized oocytes, high-quality embryos or achievement of clinical pregnancy in young and AMA women, respectively. Besides, correlations between sRAGE and age or follicle-stimulating hormone (FSH) were examined. We found that the intrafollicular sRAGE levels were higher in young patients than those in AMA patients, suggesting that the sRAGE levels were inversely correlated with age. In young patients, sRAGE showed no correlation with the number of retrieved oocytes, fertilized oocytes, high-quality embryos or achievement of clinical pregnancy. But it was found that AMA patients with more retrieved oocytes, fertilized oocytes and high-quality embryos demonstrated higher sRAGE levels, which were a prognostic factor for getting clinical pregnancy independent of age or FSH level. In conclusion, the sRAGE levels decrease with age. Elevated intrafollicular sRAGE levels indicate good follicular growth, fertilization and embryonic development, and successful clinical pregnancy in AMA women, while in young women, the role of sRAGE may not be so predominant.


Assuntos
Envelhecimento/metabolismo , Desenvolvimento Embrionário , Líquido Folicular/metabolismo , Oócitos/citologia , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Adulto , Feminino , Fertilização in vitro , Regulação da Expressão Gênica , Humanos , Idade Materna , Oócitos/metabolismo , Gravidez , Estudos Prospectivos
12.
Biomed Pharmacother ; 85: 756-762, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27919737

RESUMO

Acute lung injury (ALI) as a serious disease with high mortality has been emphasized as a threat to human health and life. Accumulating studies demonstrated that PM2.5 plays a significant role in metabolic and lung diseases. Histone deacetylases 3 (HDAC3) is an important regulator in control of gene transcription, required in up-regulation of inflammation-related signaling, and has been known as a key hotpot in treating a lot of chronic inflammatory diseases. TGF-ß/Smad signaling pathway has been proven to be of significance in fibrosis development. Our results found that PM2.5 induced lung function injury in WT mice with a inflammatory responses through the activation of TGF-ß/Smad signaling pathways, resulting in lung injury. Of note, HDAC3-deficient mice after PM2.5 administration further promoted TGF-ß/Smad signaling pathways activation. In addition, TLR4, p-NF-κB and p-IκBα indicated that HDAC3 knockout mice have a higher inflammation-related signals expression in lung tissue than WT mice after PM2.5 administration, resulting in pro-inflammatory cytokines releasing. Moreover, in vitro experiment of lung epithelial cells challenged with PM2.5, further indicated that TGF-ß/Smad2/3 was involved in fibrosis development, leading to inflammation response. Also, the activation of TLR4/NF-κB could be observed in PM2.5-induced lung epithelial cells, leading to inflammation infiltration. These results indicate a new therapeutic target to protect against lung injury caused by PM2.5.


Assuntos
Histona Desacetilases/metabolismo , Lesão Pulmonar/induzido quimicamente , NF-kappa B/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Deleção de Genes , Regulação da Expressão Gênica/fisiologia , Histona Desacetilases/genética , Lesão Pulmonar/metabolismo , Camundongos , NF-kappa B/genética , Tamanho da Partícula , Material Particulado/química , Material Particulado/toxicidade , Proteína Smad2/genética , Proteína Smad3/genética , Fator de Crescimento Transformador beta/genética
13.
Biol Chem ; 398(7): 785-792, 2017 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-28002023

RESUMO

Valproic acid (VPA) has been suggested to be a histone deacetylase inhibitor (HDACI). Our present study revealed that VPA at 1 mm, which had no effect on cell proliferation, can significantly increase the sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin (DDP). VPA treatment markedly decreased the mRNA and protein levels of ABCA1, while had no significant effect on ABCA3, ABCA7 or ABCB10. Luciferase reporter assays showed that VPA can decrease the ABCA1 promoter activity in both A549 and H358 cells. VPA treatment also decreased the phosphorylation of SP1, which can bind to -100 and -166 bp in the promoter of ABCA1. While the phosphorylation of c-Fos and c-Jun were not changed in VPA treated NSCLC cells. Over expression of HDAC2 attenuated VPA induced down regulation of ABCA1 mRNA expression and promoter activities. Over expression of HDAC2 also attenuated VPA induced DDP sensitivity of NSCLC cells. These data revealed that VPA can increase the DDP sensitivity of NSCLC cells via down regulation of ABCA1 through HDAC2/SP1 signals. It suggested that combination of VPA and anticancer drugs such as DDP might be great helpful for treatment of NSCLC patients.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/farmacologia , Regulação para Baixo/efeitos dos fármacos , Histona Desacetilase 2/metabolismo , Neoplasias Pulmonares/patologia , Ácido Valproico/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sinergismo Farmacológico , Histona Desacetilase 2/genética , Humanos , Fator de Transcrição Sp1/metabolismo , Transcrição Gênica/efeitos dos fármacos
14.
Respir Med ; 121: 48-58, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27888992

RESUMO

BACKGROUND: Obesity worsens asthma control partly through enhanced airway neutrophilia, altered lung mechanics and comorbidities, including obstructive sleep apnea syndrome, gastroesophageal reflux disease and depression. Although controversial, obesity may also cause poorer outcomes in acute asthma. IL-17 is associated with neutrophilic inflammation, steroid resistance and severe asthma, but its importance in the association between asthma and obesity is unknown. OBJECTIVE: To investigate the role of IL-17 in obese asthma in both acute and stable settings. METHODS: Both stable (n = 177) and acute (n = 78) asthmatics were recruited and categorized into lean (n = 77 and 39 respectively), overweight (n = 41 and 17 respectively) and obese (n = 59 and 22 respectively) groups and compared for clinical characteristics, including sputum and plasma IL-17 protein concentrations, sputum cellularity, spirometry and comorbidities. Correlations of IL-17 expression with other measures were explored. RESULTS: In stable subjects, airway neutrophilia and IL-17 concentrations were most prominent in the obese, and correlated positively with each other. Significant increase in plasma IL-17 levels was also noted and associated with elevated depressive symptoms in obesity. In acute asthma, IL-17 expression, like most other clinical measures, was similar among lean, overweight and obese groups, but was higher in acute versus stable asthma subjects, with sputum IL-17 correlating positively with sputum neutrophils and negatively with FEV1 and plasma IL-17 showing a positive connection to airway eosinophilia during exacerbation. CONCLUSIONS: IL-17 contributes to worse disease control in obese asthma through enhancing airway neutrophilia and depression, and may implicate in asthma exacerbations. Effects of adiposity on acute asthma remain uncertain.


Assuntos
Asma/imunologia , Interleucina-17/análise , Obesidade/imunologia , Escarro/imunologia , Doença Aguda , Adulto , Asma/complicações , Índice de Massa Corporal , Depressão/imunologia , Feminino , Humanos , Interleucina-17/sangue , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Obesidade/complicações , Sobrepeso/complicações , Sobrepeso/imunologia , Escarro/citologia , Magreza/imunologia
15.
J Gastroenterol ; 51(2): 119-29, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26045391

RESUMO

BACKGROUND: Gastric cancer (GC) is known for its lymph node metastasis and outstanding morbidity and mortality. Thus, improvement in the current knowledge regarding the molecular mechanism of GC is urgently needed to discover novel biomarkers involved in its progression and prognosis. Several long, non-coding RNAs (lncRNAs) play important roles in gastric tumorigenesis and metastasis. However, the signature of lncRNA-associated metastasis in GC is not fully clarified. METHODS: We determined the lncRNA and mRNA expression profiles correlating to GC with or without lymph node-metastasis based on microarray analysis. Twelve differentially expressed lncRNAs and six differentially expressed mRNAs were validated by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay. RESULTS: The relationships between the aberrantly expressed lncRNAs XLOC_010235 or RP11-789C1.1 and lymph node metastasis, pathologic metastasis status, distal metastasis and TNM (tumour, node, and metastasis) stage were found to be significantly different. Via survival analysis, patients who had high-expressed XLOC_010235 or low-expressed RP11-789C1.1 showed significantly worse survival than patients with inverse-expressed XLOC_010235 or RP11-789C1.1. CONCLUSION: In summary, this current study highlights some evidence regarding the potential role of lncRNAs in GC and posits that specific lncRNAs can be identified as novel, poor prognostic biomarkers in GC.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/secundário , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Neoplasias Gástricas/genética , Adenocarcinoma/patologia , Idoso , Biomarcadores Tumorais/genética , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Neoplasias Gástricas/patologia
16.
Respir Care ; 60(1): 128-34, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25249648

RESUMO

INTRODUCTION: The role of inflammation and immunity in COPD treatment is increasingly being recognized. The relationship between anti-inflammation/immunoregulation and emphysema in COPD lungs remains to be elucidated. The aim of this study was to investigate the effects of azithromycin (Azm) on the development of emphysema in smoking-induced COPD in rats. METHODS: Sprague-Dawley rats (n = 50) were randomly assigned to normal, COPD, saline-treated, Azm-treated, and levofloxacin-treated (Lev) groups. The effects of treatment were assessed by measuring the levels of vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assay and measuring the numbers of neutrophil and macrophage in bronchoalveolar lavage fluid, vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR2) protein expression by western blotting. Lung function measurements and histopathological evaluations (mean linear intercept and destructive index) were performed. RESULTS: FEV0.3/FVC and peak expiratory flow were lower in the COPD group than in the normal group. Mean linear intercept and destructive index were lower in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. The numbers of neutrophil and macrophage in bronchoalveolar lavage fluid were lower in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. As confirmed by western blotting, the levels of VEGF in lung homogenates were higher in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. VEGFR2 protein expression was higher in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. CONCLUSIONS: Azm attenuates pulmonary emphysema by partly reversing the decrease in the numbers of inflammatory cells (neutrophil and macrophage) and VEGF secretion and VEGFR2 protein expression in smoking-induced COPD in rats.


Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/tratamento farmacológico , Animais , Líquido da Lavagem Broncoalveolar/citologia , Modelos Animais de Doenças , Volume Expiratório Forçado , Pulmão/química , Macrófagos , Masculino , Neutrófilos , Pico do Fluxo Expiratório , Pneumonia/tratamento farmacológico , Pneumonia/etiologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Enfisema Pulmonar/etiologia , Enfisema Pulmonar/patologia , Ratos , Ratos Sprague-Dawley , Fumar , Fator A de Crescimento do Endotélio Vascular/análise , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/análise , Capacidade Vital
17.
Int J Clin Exp Pathol ; 8(11): 14365-73, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26823752

RESUMO

The Japanese Gastric Cancer Treatment Guidelines (third edition) have assigned No. 7 station left gastric artery lymph nodes (LNs) to the D1 range of lymphatic dissection. We investigated the clinicopathological characteristics, survival impact, and appropriateness of ascribing No. 7 station LNs to D1 lymphadenectomy in gastric cancer. Patients (n=608) undergoing radical resection with No. 7 station LN dissection were recruited between January 1997 and June 2008. They were subdivided into four groups: N0, no LN metastasis; D1, LN without No. 7 station LN metastasis in the D1 lymphadenectomy region; No. 7, No. 7 station LN without LN metastasis in the D2 lymphadenectomy region; and D2, LN without No. 7 station LN metastasis in the D2 lymphadenectomy region. Of these, 17.2% (n=105) were positive for No. 7 LN metastasis, an important, independent prognostic factor associated with poor clinicopathological parameters, advanced tumor stage, and reduced survival. Tumor behavior in the No. 7 group was similar to that in the D2 group, but poorer than in the D1 group in terms of advanced tumor stage, with 5-year survival rates of 34.3%, 25.9% and 54.6%, respectively. Five-year survival rates in the No. 7 group were comparable to those in the D2 group (P>0.05), but significantly lower than in the D1 group (P<0.05). Logistic multivariate regression analysis established No. 3 and 9 station LN metastasis, node classification, and tumor-node-metastasis stage as independent risk factors for No. 7 station LN metastasis. Thus, No. 7 station LNs should be ascribed to D2 lymphadenectomy in gastric cancer.


Assuntos
Excisão de Linfonodo/métodos , Linfonodos/patologia , Linfonodos/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Distribuição de Qui-Quadrado , Feminino , Gastrectomia , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/mortalidade , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Estadiamento de Neoplasias , Razão de Chances , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/mortalidade , Fatores de Tempo , Resultado do Tratamento
18.
World J Gastroenterol ; 20(40): 14927-33, 2014 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-25356053

RESUMO

AIM: To study the effect of somatostatin in patients with advanced gastric cancer who received D2 lymphadenectomy and vagina vasorum dissection. METHODS: Using a prospective, single-blind, placebo-controlled design, patients with advanced gastric cancer were randomized into a study group (n = 61) and a control group (n = 59). Patients in the study group were given somatostatin for 5-7 d starting 6 h after the operation, and patients in the control group were given normal saline. Preoperative and nonoperative complications in the perioperative period, as well as different types of postoperative drainage in the two groups were compared. RESULTS: There was no significant difference between the study group and the control group for preoperative clinicopathological indicators. We found no significant difference between the two groups for the overall incidence of complications, but a lower percentage of peritoneal effusion was observed in the treatment group (1.6% vs 10.2%, P < 0.05). There were no significant differences between the two groups in the incidence of postoperative pancreatic dysfunction and chylous fistula. However, there were significant differences in the amylase concentration in drainage fluid, volume and duration of drainage, volume and duration of chylous fistula and peritoneal drainage, and volume and duration of gastric tube drainage. The study group did not show any increase in mean hospitalization cost and the cost reduced when the postoperative complications occurred. CONCLUSION: Postoperative somatostatin reduces volume and duration of surgical drainage and related complications. Somatostatin may improve safety of gastric cancer surgery, reducing postoperative complications and promoting recovery.


Assuntos
Antineoplásicos/administração & dosagem , Gastrectomia/métodos , Excisão de Linfonodo , Somatostatina/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Antineoplásicos/efeitos adversos , Quimioterapia Adjuvante , China , Drenagem , Esquema de Medicação , Feminino , Gastrectomia/efeitos adversos , Humanos , Excisão de Linfonodo/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Método Simples-Cego , Somatostatina/efeitos adversos , Neoplasias Gástricas/patologia , Fatores de Tempo , Resultado do Tratamento
19.
Zhong Yao Cai ; 37(4): 610-1, 2014 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-25345135

RESUMO

OBJECTIVE: To investigate the chemical constituents of ethyl acetate of Tetrastigma planicaule. METHODS: The ethyl acetate fraction was isolated and purified by repeated silica gel chromatography and recrystallization. The structures of compounds were identified by physical-chemical methods and spectral data such as MS, 1H-NMR, 13C-NMR, etc. RESULTS: Six compounds were identified as gheddic acid (I), tricosanol (II), beta-sitosterol (III), palmitic acid (IV), ethyl gallate (V) and vanillin (VI), respectively. CONCLUSION: Compounds I, II, V and VI are isolated from this plant for the first time.


Assuntos
Álcoois/química , Ácido Gálico/análogos & derivados , Plantas Medicinais/química , Vitaceae/química , Acetatos , Álcoois/isolamento & purificação , Benzaldeídos/química , Benzaldeídos/isolamento & purificação , Ácido Gálico/química , Ácido Gálico/isolamento & purificação , Estrutura Molecular
20.
Arch Med Res ; 45(2): 132-7, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24316394

RESUMO

BACKGROUND AND AIMS: The objective of this observational study was to determine whether there is an association between atrial fibrillation (AF) and uric acid and to identify the risk markers for AF in obstructive sleep apnea (OSA). METHODS: Consecutive patients with newly diagnosed OSA were screened at baseline. The final study population consisted of 516 patients. One hundred and eight patients had AF. Demographic, clinical, laboratory, and echocardiographic characteristics were carefully recorded. Logistic regression was used for the multivariate analysis of independent risk factors. RESULTS: Uric acid, triglyceride, high-density lipoprotein, C-reactive protein (CRP), left atrial diameter, interventricular septum thickness, apnea hypopnea index, and Epworth sleepiness scale were significantly higher in OSA patients with AF than in those without AF (p <0.05). Among these patients, multiple logistic analyses indicated the independent risk factors for AF occurrence in the OSA subjects included serum uric acid level, left atrial diameter, percentage of time with SaO2 <90%, CRP. The diagnosis analysis showed that higher uric acid, CRP, left atrial diameter and percentage of time with SaO2 <90% had a significant ability to reflect the presence of AF occurrence. CONCLUSIONS: The novel finding of this study is that the occurrence of AF in OSA patients is strongly related to serum uric acid level, left atrial diameter, percentage of time with SaO2 <90% and CRP level. These results may be helpful for monitoring AF occurrence in OSA patients.


Assuntos
Fibrilação Atrial/sangue , Apneia Obstrutiva do Sono/sangue , Ácido Úrico/sangue , Adulto , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/fisiopatologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Apneia Obstrutiva do Sono/complicações
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