RESUMO
BACKGROUND: Our previous study has revealed that EphA7 was upregulated in patient-derived esophageal squamous cell carcinoma (ESCC) xenografts with hyper-activated STAT3, but its mechanism was still unclear. MATERIALS AND METHODS: To assess the association between EphA7 and STAT3, western blotting, immunofluorescence, ChIP assay, and qRT-PCR were conducted. Truncated mutation and luciferase assay were performed to examine the promoter activity of EphA7. CCK-8 assay and colony formation were performed to assess the proliferation of ESCC. Cell-derived xenograft models were established to evaluate the effects of EphA7 on ESCC tumor growth. RNA-seq analyses were used to assess the effects of EphA7 on related signals. RESULTS: In this study, EphA7 was found upregulated in ESCC cell lines with high STAT3 activation, and immunofluorescence also showed that EphA7 was co-localized with phospho-STAT3 in ESCC cells. Interestingly, suppressing STAT3 activation by the STAT3 inhibitor Stattic markedly inhibited the protein expression of EphA7 in ESCC cells, in contrast, activation of STAT3 by IL-6 obviously upregulated the protein expression of EphA7. Moreover, the transcription of EphA7 was also mediated by the activation of STAT3 in ESCC cells, and the -2000â¼-1500 region was identified as the key promoter of EphA7. Our results also indicated that EphA7 enhanced the cell proliferation of ESCC, and silence of EphA7 significantly suppressed ESCC tumor growth. Moreover, EphA7 silence markedly abolished STAT3 activation-derived cell proliferation of ESCC. Additionally, RNA-seq analyses indicated that several tumor-related signaling pathways were significantly changed after EphA7 downregulation in ESCC cells. CONCLUSION: Our results showed that the transcriptional expression of EphA7 was increased by activated STAT3, and the STAT3 signaling may act through EphA7 to promote the development of ESCC.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Receptor EphA7 , Fator de Transcrição STAT3 , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Receptor EphA7/metabolismoRESUMO
As a systematic research at basin scale, this study explored the composition and concentration characteristics of 16 priority polycyclic aromatic hydrocarbons (PAHs) in sediments, water, and suspended particulate matter (SPM) in the water systems (rivers, lakes, and reservoirs) in the Hai River Basin through literature review. The sources and the ecosystem risks of PAHs in the sediments in the entire basin were specially discussed with diagnostic ration, PAHs composition, and an improved risk quotient method. Results showed that the total concentration of PAHs varied from 99.65 to 25,303 ng g(-1) dry weight in sediments, from 51.0 to 559.1 ng L(-1) in water, and from 4528 to 51,080 ng g(-1) dry weight in SPM, respectively. The dominant PAHs in the three examined phases were 2-3 rings in most waterbodies. PAHs in the rivers were from mixed sources (petrogenic and pyrolytic inputs), whereas those in lakes and reservoirs were mainly from biomass combustion and petroleum combustion. PAHs in the entire basin exhibited moderate to high ecological risk, and the rivers (especially Hai River, Jiyun River, Chaobai River, and Beiyun River) suffered higher ecological risk than reservoirs and lakes. Most of the rivers with higher PAHs risk flow through or around megacity Beijing and Tianjin.
Assuntos
Monitoramento Ambiental , Hidrocarbonetos Policíclicos Aromáticos/análise , Rios/química , Poluentes Químicos da Água/análise , China , Medição de Risco , Poluição Química da Água/estatística & dados numéricosRESUMO
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor of the digestive tract, which is very harmful to human health. The JAK-STAT signaling pathway is a recognized carcinogenic pathway that plays a role in the proliferation, apoptosis, migration, and invasion of a variety of cancer cells. Some studies have shown that the activation status of STAT3 affects the expression of KIRREL3. However, the expression of KIRREL3 in ESCC and its relationship with KIRREL3 or the JAK-STAT signaling pathway is still unclear. METHODS: In this study, we used immunohistochemistry and western blotting to analyze the protein expression levels of KIRREL3 in tumor tissues and ESCC cell lines. We applied proliferation assays, plate clone formation assays, Transwell assays, flow cytometry analysis, and CDX animal models to examine the role of KIRREL3 in ESCC. RESULTS: The results indicate that KIRREL3 is highly expressed to varying degrees in ESCC tissues and cell lines. Knocking down KIRREL3 expression in ESCC cells could correspondingly inhibit cell proliferation, colony formation, invasion, and migration, and had some effects on cell cycle progression and apoptosis. In addition, overexpressing KIRREL3 in these cells had opposite effects. Tumor formation in nude mice experiments also confirmed that KIRREL3 is involved in the growth of ESCC cells in vivo. CONCLUSIONS: These data suggest that KIRREL3 plays a key role in the development of ESCC, and KIRREL3 is a potential new target for the early diagnosis and clinical treatment of this disease.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Proteínas de Membrana , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/metabolismo , Camundongos NusRESUMO
Eutrophication has become one of the most serious problems threatening the lakes/reservoirs in China over 50 years. Evaluation of eutrophication is a multi-criteria decision-making process with uncertainties. In this study, a cloud matter element (CME) model was developed in order to evaluate eutrophication level objectively and scientifically, which incorporated the randomness and fuzziness of eutrophication evaluation process. The elements belonging to each eutrophication level in the CME model were determined by means of certainty degrees through repeated simulations of cloud model with reasonable parameters of expectation Ex, entropy En, and hyper-entropy He. The weights of evaluation indicators were decided by a combination of entropy technology and analytic hierarchy process method. The neartudes of water samples to each eutrophication level of lakes/reservoirs in the CME model were generated and the eutrophication levels were determined by maximum neartude principal. The proposed CME model was applied to evaluate eutrophication levels of 24 typical lakes/reservoirs in China. The results of the CME model were compared with those of comprehensive index method, matter element model, fuzzy matter element model, and cloud model. Most of the results obtained by the CME model were consistent with the results obtained by other methods, which proved the CME model is an effective tool to evaluate eutrophication.
Assuntos
Monitoramento Ambiental/métodos , Monitoramento Ambiental/estatística & dados numéricos , Eutrofização , Lagos/química , China , Modelos TeóricosRESUMO
BACKGROUND: We and others have previously shown that the STAT3 signaling pathway is activated in some esophageal squamous cell carcinoma (ESCC) cells and is required for the survival and growth of these primary ESCC-derived xenografts. It has also been shown that the natural polyphenol curcumin is an effective anti-tumor agent. METHODS: Luciferase assay and immunoblotting were performed to examine whether curcumin suppressed STAT3 signaling. CCK-8 assay and xenografts were utilized for analyzing ESCC cell growth in culture and mice. Soft agar assay was carried out to determine the colony formation ability of ESCC cells in the presence or absence of curcumin. Cell death and cell cycle were assessed by In CELL Analyzer 2000. Immunohistochemistry and TUNEL assay were used for detecting apoptosis in ESCC tisuses. Molecular docking was performed to evaluate the interaction of curcumin with JAK2. JAK2 activity was assessed using an in vitro cell-free system. HE staining was used to evaluate the ESCC tissues. RESULTS: The natural polyphenol curcumin inhibited STAT3 phosphorylation rapidly and blocked STAT3-mediated signaling in ESCC cells. It also induced growth arrest and apoptosis in cultured ESCC cells, which were attenuated by enforced expression of STAT3. Furthermore, curcumin preferentially blocked the growth of primary ESCC-derived xenografts that harbored activated STAT3. CONCLUSIONS: Curcumin is able to exert anti-tumor action through inhibiting the STAT3 signaling pathway. Giving its wide use in traditional medicines with low toxicity and few adverse reactions, it is conceivable that curcumin might be further explored as a unique STAT3 inhibitor for anti-cancer therapies.
Assuntos
Curcumina/farmacologia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Fator de Transcrição STAT3/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Camundongos , Camundongos SCID , Simulação de Acoplamento Molecular , Transdução de Sinais/efeitos dos fármacos , Análise de Sobrevida , Transfecção , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To study the pathogen and characteristics of viral diarrhea in children in Changchun area. METHODS: 460 stools specimens were collected from children with acute diarrhea cured in the childrens, hospital of Changchun in 2010. Rotavirus were detected by ELISA, caliceverus and astrovirus were detected by reverse transcription-polymerase chain reactions (RT-PCR), adenovirus were detected by polymerase chain reactions (PCR). RESULTS: A total of 460 specimens were detected. The detection rate of rotavirus, caliceverus, astrovious, adenovious respectively is 35.22%, 20.43%, 9.78%, 3.70%, the detectablerate of mixed infection is 7.61%, children under 2 years old were the major patient. The main genotypes of the virus: rotavirus (G3P[8]), caliceverus (GII-4), astrovious (type I), adenovious (Ad41). CONCLUSION: Rotavirus is the main pathogen in Changchun. Followed by caliceverus, astrovious, adenovious.