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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(4): 686-692, 2021 Jul.
Artigo em Zh | MEDLINE | ID: mdl-34323050

RESUMO

OBJECTIVE: To establish an artificial intelligence-assisted diagnosis system for molecular subtyping of colorectal cancer (CRC). METHODS: 812 whole-slide images (WSIs) of 422 patients were selected from the database of The Cancer Genome Atlas (TCGA) and were put into the training set (75%) and the test set (25%). The slides were stored in the www.paiwsit.com database. We preprocessed and segmented the slides based on the labelling results of experienced pathologists to generate a training set of more than 4 million labeled samples. Finally, deep learning models were adopted for training. RESULTS: After training with several convolutional neural network models, we tested the performance of the trained deep learning model on the test set of 203 WSIs from 110 patients, and our model achieved an accuracy of 53.04% at patch-level and 51.72% at slide-level, while the accuracy of CMS2 (one of a consensus of four subtypes for CRC) at slide-level was as high as 75.00%. CONCLUSION: This study is of great significance to the promotion of colorectal cancer screening and precision treatment.


Assuntos
Neoplasias Colorretais , Aprendizado Profundo , Inteligência Artificial , Humanos , Redes Neurais de Computação
2.
Environ Sci Technol ; 52(23): 13935-13941, 2018 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-30384584

RESUMO

Even though sex hormone disrupting effects of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are widely understood, similar effects associated with new flame retardants (NFRs) have not been so well studied. This study aimed to explore the sex hormone disruption of NFRs and their interactions with PCBs and PBDEs through the conduct of an ecological study in an e-waste dismantling and control region in South China. Questionnaires and blood samples were collected from local adult residents. Results of generalized additive model and linear regression analyses indicate that several species of NFRs showed similar disrupting effects with PBDE congeners on female follicle-stimulating hormone (FSH) and male testosterone. Judged by the curved shape and statistical significance, ΣNFR (sum of 8 species of NFRs) showed stronger disrupting effects on male testosterone and female FSH compared to ΣPBDE (sum of 13 congeners of PBDEs). The interactions induced by NFRs complicated the original sex hormone disruption led by PCBs and PBDEs. The disrupting effects and interactions induced by NFRs decreased female FSH levels in the exposed group. Comprehensive evaluation is needed to provide the evidence base for judging the health risks arising from the increased usage of NFRs.


Assuntos
Poluentes Ambientais , Retardadores de Chama , Bifenil Polibromatos , Bifenilos Policlorados , Adulto , China , Feminino , Hormônios Esteroides Gonadais , Éteres Difenil Halogenados , Humanos , Masculino , Éteres Fenílicos
3.
J Asthma ; 53(10): 1090-3, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27144426

RESUMO

INTRODUCTION: Tracheal papilloma presenting as asthma is a rare occurrence. CASE STUDY: We report a case of a 32-year-old male patient who presented with features of asthma. Flexible bronchoscopy demonstrated a large growth arising from the lower end of the trachea. Successful treatment using snare loop and argon plasma coagulation (APC) of the polyploidal growth was performed via flexible bronchoscope. RESULTS: The patient had immediate relief of airway obstruction and histopathological examination of the neoplasm demonstrated features of papilloma. CONCLUSION: Primary tracheal papilloma is mimicker of asthma, CT scan should be considered in patients with persistent chronic cough, or stridor. Endoscopic papillectomy is a safe and effective treatment and should be considered as first-line therapy for tracheal papilloma.


Assuntos
Asma/diagnóstico , Papiloma/diagnóstico , Neoplasias da Traqueia/diagnóstico , Adulto , Asma/diagnóstico por imagem , Broncoscopia , Humanos , Masculino , Papiloma/diagnóstico por imagem , Papiloma/cirurgia , Tomografia Computadorizada por Raios X , Neoplasias da Traqueia/diagnóstico por imagem , Neoplasias da Traqueia/cirurgia
4.
Cancer Sci ; 105(3): 265-71, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24418124

RESUMO

Recent studies have identified a class of small non-coding RNA molecules, named microRNA (miRNA), that is dysregulated in malignant brain glioblastoma. Substantial data have indicated that miRNA-16 (miR-16) plays a significant role in tumors of various origins. This miRNA has been linked to various aspects of carcinogenesis, including cell apoptosis and migration. However, the molecular functions of miR-16 in gliomagenesis are largely unknown. We have shown that the expression of miR-16 in human brain glioma tissues was lower than in non-cancerous brain tissues, and that the expression of miR-16 decreased with increasing degrees of malignancy. Our data suggest that the expression of miR-16 and nuclear factor (NF)-κB1 was negatively correlated with glioma levels. MicroRNA-16 decreased glioma malignancy by downregulating NF-κB1 and MMP9, and led to suppressed invasiveness of human glioma cell lines SHG44, U87, and U373. Our results also indicated that upregulation of miR-16 promoted apoptosis by suppressing BCL2 expression. Finally, the upregulation of miR-16 in a nude mice model of human glioma resulted in significant suppression of glioma growth and invasiveness. Taken together, our experiments have validated the important role of miR-16 as a tumor suppressor gene in glioma growth and invasiveness, and revealed a novel mechanism of miR-16-mediated regulation in glioma growth and invasiveness through inhibition of BCL2 and the NF-κB1/MMP-9 signaling pathway. Therefore, our experiments suggest the possible future use of miR-16 as a therapeutic target in gliomas.


Assuntos
Neoplasias Encefálicas/metabolismo , Proliferação de Células , Glioma/metabolismo , MicroRNAs/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Transdução de Sinais , Animais , Apoptose , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Glioma/patologia , Humanos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Subunidade p50 de NF-kappa B/metabolismo , Invasividade Neoplásica , Transplante de Neoplasias , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Interferência de RNA , Carga Tumoral
5.
Environ Sci Technol ; 48(19): 11196-203, 2014 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-25198778

RESUMO

Wet deposition is an effective and important mechanism for removal of atmospheric pollutants, particularly in urban regions. To examine the effectiveness of natural and anthropogenic factors in such removal mechanisms, we conducted a study in Guangzhou, a mega metropolitan center in South China. Rainwater and dry particle deposition samples were simultaneously collected from Guangzhou during the entire year of 2010, and analyzed for polybrominated diphenyl ethers (PBDEs), a group of pollutants mainly derived from industrial and household consumer products. Concentrations of ΣPBDE (sum of the 21 congeners of PBDEs) and BDE-209 in wet deposition samples ranged from 0.11 to 640 (average: 23 ± 36 ng L(-1)) and 0.071 to 420 (average: 20 ± 31 ng L(-1)), respectively. Assessed by conditional inference tree, particulate matter was recognized as the most important factor controlling concentration levels of PBDEs. The combined wet and dry deposition flux of ΣPBDE (1.4 (± 1.2) × 10(4) ng m(-2) quarter(-1)) in the first quarter of 2010 was not significantly different from that (1.3 (± 0.46) × 10(4) ng m(-2) quarter(-1)) in the fourth quarter, indicating that source control measures implemented by local governments for the 16th Asian Games and 10th Asian Para Games (held in November and December 2010, respectively) were ineffective in reducing the loadings of atmospheric PBDEs. In addition, the lower removal efficiency of ΣPBDE was found in the fourth quarter compared to other quarters. This result suggested that rain interventions conducted to maintain clear weather conditions for the Asian Games turned out to lower the efficacy for removal of PBDEs by wet deposition.


Assuntos
Éteres Difenil Halogenados/análise , China , Cidades , Monitoramento Ambiental/métodos , Poluentes Ambientais/análise , Material Particulado/análise , Chuva , Estações do Ano
6.
J Hazard Mater ; 469: 133915, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38452669

RESUMO

Neonicotinoids are widely used insecticides that have raised considerable concerns for both environmental and human health. However, there lack of comprehensive evaluation of their accumulation in surface water ecosystems and exposure to various human groups. Additionally, there's a distinct lack of scientific evidence describing the carcinogenic and non-carcinogenic impacts of neonicotinoids from surface water. Using an integrated approach employing the Relative Potency Factor (RPF), Hazard Index (HI), and Monte Carlo Simulation (MCS), the study assessed neonicotinoid exposure and risk to four demographic groups via dermal contact and mistaken oral intake pathways in the Yangtze River Basin (YRB), China. Neonicotinoid concentrations range from 0.1 to 408.12 ng/L, indicating potential risk (10-3 to 10-1) across the studied demographic groups. The Incremental Lifetime Cancer Risk (ILCR) for dermal contact was within a moderate range of 2.00 × 10-3 to 1.67 × 10-2, while the mistaken oral intake was also within a moderate range of 3.07 × 10-3 to 7.05 × 10-3. The Hazard Index (HI) for dermal exposure ranged from 1.49 × 10-2 to 0.125, while for mistaken oral intake, it varied between 2.69 × 10-2 and 0.14. The findings highlight the importance of implementing specific interventions to address neonicotinoid exposure, especially among demographic groups that are more susceptible. This research underscores the urgent need for targeted strategies to address neonicotinoid risks to vulnerable populations within the YRB while contributing to insights for effective policies to mitigate neonicotinoid exposure in surface water ecosystems globally.


Assuntos
Inseticidas , Poluentes Químicos da Água , Humanos , Inseticidas/toxicidade , Inseticidas/análise , Água , Rios , Ecossistema , Neonicotinoides/toxicidade , China , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise
7.
Tissue Barriers ; : 2256641, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37819188

RESUMO

Although the majority of the population will be protected due to the advent and widespread use of the HPV vaccine, the treatment of cervical cancer for all causes, including HPV-negative cervical cancer, is still worthy of further research. The focal point of this study was Canadine's inhibition of epithelial-mesenchymal transformation (EMT) in cervical cancer. Immunoblotting, wound healing and tumor invasion experiments showed that low concentration of Canadine could inhibit the EMT process, proliferation and migration of HT-3 cells (HPV-negative cell line). Combined with GEO database, it was found that the expression levels of several genes highly expressed in cervical tumor tissues could be inhibited by Canadine, especially MAGEA3. Further experiments confirmed that the inhibition of Canadine on MAGEA3 protein increased with time. The small interference and overexpression plasmid of MAGEA3 were designed and verified. In HT-3 cells, when MAGEA3 levels were directly decreased, mesenchymal phenotypic markers were decreased and epithelial phenotypic markers were increased. The opposite result was obtained by overexpression of MAGEA3. In addition, the inhibition of EMT due to the reduction of endogenous MAGEA3 by Canadine was also offset by the overexpression of exogenous MAGEA3. The study concludes that Canadine inhibits EMT of cervical cancer by inhibiting MAGEA3.

8.
J Cardiovasc Transl Res ; 16(1): 65-76, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35708897

RESUMO

Abdominal aortic aneurysm (AAA) is a fatal vascular disease. Vascular smooth muscle cells (VSMCs) play a crucial role in the pathogenesis of AAA. Increasing evidence has shown that Yes-associated protein (YAP) is involved in diverse vascular diseases. However, the role of YAP in AAA remains unclear. The current study aimed to determine the role of YAP in AAA formation and the underlying mechanism. We found that YAP expression in VSMCs was markedly decreased in human and experimental AAA samples. Furthermore, VSMC-specific YAP overexpression prevented several pathogenic factor-induced AAA. Mechanistically, YAP overexpression in VSMCs promoted latent transforming growth factor-ß binding protein 4 (LTBP4) expression, an important factor in elastic fiber assembly. Finally, silencing of LTBP4 in VSMCs abolished the protective role of YAP in AAA formation in vivo. Our results suggest that YAP promotes LTBP4-mediated elastic fibril assembly in VSMCs, which mitigates elastin degradation and AAA formation.


Assuntos
Aneurisma da Aorta Abdominal , Músculo Liso Vascular , Proteínas de Sinalização YAP , Animais , Humanos , Camundongos , Aneurisma da Aorta Abdominal/metabolismo , Modelos Animais de Doenças , Tecido Elástico/metabolismo , Tecido Elástico/patologia , Proteínas de Ligação a TGF-beta Latente/metabolismo , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/patologia , Proteínas de Sinalização YAP/metabolismo
9.
Sci Total Environ ; 858(Pt 1): 159746, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36306844

RESUMO

E-waste handling activities release large quantities of polychlorinated biphenyls (PCBs) and halogen flame retardants (HFRs) into the surrounding area, creating a high exposure risk for local residents. However, the possibility of PCBs and HFRs exposure contributing to renal injury has not been extensively studied. To fill this knowledge gap, we conducted an epidemiological analysis of adolescents and adults recruited from an e-waste recycling area and a control area. Some PCBs and HFRs compounds were statistically significantly associated with the levels of ß2-microglobulin (ß2-MG), blood urea nitrogen (BUN), serum creatinine (SCr), and uric acid, with thyroid hormone-related genes found to partly mediate these associations. The interactions of PCBs and HFRs with metals also influenced renal function indexes. Exposure to high concentrations of PCBs and HFRs resulted in higher levels of ß2-MG and lower levels of BUN and SCr in the exposed group. As indicated by the elevated ß2-MG levels, high exposure to PCBs and HFRs may increase the risk of early renal injury for adolescents. These findings help to clarify the impacts of PCBs and HFRs on renal function and highlight the need to protect the health of residents in regions impacted by e-waste handling activities.


Assuntos
Resíduo Eletrônico , Retardadores de Chama , Bifenilos Policlorados , Adolescente , Adulto , Humanos , Resíduo Eletrônico/análise , Monitoramento Ambiental , Retardadores de Chama/análise , Éteres Difenil Halogenados/análise , Halogênios/análise , Rim/fisiologia , Rim/química , Bifenilos Policlorados/análise , Reciclagem
10.
Zhonghua Jie He He Hu Xi Za Zhi ; 35(9): 679-82, 2012 Sep.
Artigo em Zh | MEDLINE | ID: mdl-23158071

RESUMO

OBJECTIVE: To study the clinical characteristics, chest imaging, pathology, diagnosis and treatment of clear cell tumor of the lung (CCTL). METHODS: Seven cases of CCTL diagnosed from January 2000 to December 2010 in our hospital, and 38 cases from literatures published in mainland of China, were retrospectively analyzed. RESULTS: The age of the patients was (44 ± 18) years, with equal sex distribution. In most of the patients, the lesions were incidentally found during routine examinations. Chest roentgenogram or CT scan showed a homogenous, rounded opacity (solitary nodule) of (3.2 ± 1.4) cm in diameter. Contrast-enhanced CT scans revealed a sign of intense enhancement because of these tumors were highly vascular, containing capillaries and sinusoidal vessels in some patients. Pathologic examination showed rounded and oval tumor cells with abundant clear cytoplasm, distinct cell borders, and cytoplasm rich in periodic acid Schiff-positive glycogen granules. Immunohistochemically, CCTL expressed melanocytic and myogenic markers, such as human melanoma black-45 (HMB-45), HMSA-1 and actin. But its epithelial markers were negative. Resection via operation was the only effective method till now. CONCLUSIONS: CCTL is a rare benign tumor with special features of clinical characteristics, radiology and pathology. The diagnosis is based on distinct pathologic characteristics. Earlier operation with long term follow-up is recommended.


Assuntos
Adenocarcinoma de Células Claras , Neoplasias Pulmonares , Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Huan Jing Ke Xue ; 43(1): 490-499, 2022 Jan 08.
Artigo em Zh | MEDLINE | ID: mdl-34989534

RESUMO

To study the characteristics of polychlorinated biphenyls (PCBs) in waste residue-soil-vegetable in an e-waste dismantling area and the potential health risks to humans, three samples of e-waste residue were collected, and 10 and 18 samples were taken from farmland soil and vegetables (six lettuce, six green bean, and six cabbage samples), respectively, next to the waste residue. High-resolution gas chromatography-mass spectrometry was used to detect the content of PCBs in waste residue, soil, and vegetables. The results showed that the total PCBs levels were as follows:waste residue (11938 ng·g-1, dw) > soil (45.54 ng·g-1, dw) > vegetables (11.51 ng·g-1, dw). The bio-sediment/soil enrichment factor values were as follows:lettuce samples (0.18) > green bean samples (0.05) > cabbage samples (0.01). There were 37 PCB identical homologues detected in the waste residue and soil, and 33 types were detected in vegetables, all of which were within the homologues detected in the waste residue and soil. Some homologues in the soil were correlated with cabbages (P<0.05). The column chart of PCB chlorination number in waste residues, soil, and vegetables showed that low-chlorinated biphenyls from trichlorobiphenyl to pentachlorobiphenyl mass fraction accounted for the largest proportion, accounting for 77.92%, 59.73%, and 73.96%, respectively. The proportion in the soil was relatively low, with the overall proportion showing a downward trend with increasing rate of chlorine generation. The results of the health risk assessment showed that the total HQ of PCBs in the soil and vegetables exposed to adults (male/female) and children was less than 1, which was at an acceptable level. The total CR of PCBs in the soil and vegetables exposed to adults (male/female) and children all exceeded 1×10-6, which is at an unacceptable level, and the values for adults (male/female) were higher than those for children.


Assuntos
Resíduo Eletrônico , Bifenilos Policlorados , Poluentes do Solo , Adulto , Criança , Monitoramento Ambiental , Humanos , Bifenilos Policlorados/análise , Medição de Risco , Solo , Poluentes do Solo/análise , Verduras
12.
Chemosphere ; 297: 134102, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35219707

RESUMO

Heavy metals play an important role in inducing fine particulate matter (PM2.5) related cardiovascular disease (CVD). However, most of the past researches concerned the associations between CVD mortality and the PM2.5 mass, which may not reveal the CVD mortality risk contributed by heavy metals in PM2.5. This study explored the correlations between individual heavy metals in PM2.5 and CVD mortality, identified the heavy metals that significantly contribute to PM2.5-related CVD, heart disease (HD), and cerebrovascular disease (CEV) mortality, and attempted to establish corresponding source control measures. Over a 2-year study period, PM2.5 was sampled daily in Guangzhou, China and analyzed for heavy metals. The airborne pollution and weather data, along with CVD, HD, and CEV mortality, were obtained at the same time. The excess risk (ER) of mortality was linked to the individual heavy metals using a distributed lag non-linear model. PM2.5 and most heavy metals showed significant correlations with the CVD, HD, and CEV mortality; the largest cumulative ER (LCER) values of CVD mortality associated with an interquartile range increase in the levels of lead, cadmium, arsenic, selenium, antimony, nickel, thallium, aluminum, iron, and PM2.5 were 2.43%, 2.23%, 1.66%, 2.39%, 1.19%, 1.21%, 2.69%, 3.29%, 1.74%, and 2.40%, respectively. Most heavy metals showed comparable LCER values of HD and CEV mortality. Heavy metals with the addition of PM2.5 were divided into three groups following their LCER values; lead, cadmium, arsenic, antimony, thallium, zinc, aluminum, and iron, whose contributions were greater than or equal to the average effect of the PM2.5 components, should be limited on a priority basis. These findings indicated that heavy metals play roles in the CVD, HD, and CEV mortality risk of PM2.5, and specific control measures which aimed at the emission sources should be taken to reduce the CVD mortality risk of PM2.5.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Arsênio , Doenças Cardiovasculares , Metais Pesados , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , Alumínio , Antimônio , Cádmio , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Humanos , Ferro , Metais Pesados/análise , Metais Pesados/toxicidade , Material Particulado/análise , Tálio
13.
J Dermatolog Treat ; 33(4): 2129-2136, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34060412

RESUMO

BACKGROUND: Psoriasis is chronic incurable skin inflammation. The anti-inflammatory properties of mesenchymal stem cells (MSCs) have been put forward to be involved in several inflammatory diseases. However, little was known about the role of human adipose tissue-derived stem cells (hAD-MSCs) in psoriasis. OBJECTIVE: We sought to explore the feasibility of using hAD-MSCs infusion as a therapeutic approach in psoriatic mice. METHODS: We constructed the psoriasis-like model by IMQ implication, treated with hAD-MSCs by subcutaneous injection. To evaluate the efficacy, we examined the histology, CD45 and ROS positive cells by HE and flow cytometry respectively. We also tested the key cytokines with PCR. Moreover, to achieve a better therapeutic effect, we treated the model by combing with vitamin E application. RESULTS: We found that the classic histological symptoms of psoriasis were relieved after treatment with hAD-MSCs, also, the splenic index, the infiltration of immune cells and several pro-inflammatory cytokines were decreased. Interestingly, we also found that hAD-MSCs could inhibit ROS generation. Moreover, the combination therapy of hAD-MSCs and vitamin E could promote the curative effect with greater ROS inhibition. CONCLUSION: These results suggested that hAD-MSCs could be useful for treating psoriasis by negatively regulating ROS.


Assuntos
Inflamação , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Psoríase , Espécies Reativas de Oxigênio , Tecido Adiposo/citologia , Animais , Citocinas , Dermatite/metabolismo , Dermatite/terapia , Modelos Animais de Doenças , Estudos de Viabilidade , Humanos , Inflamação/metabolismo , Inflamação/terapia , Injeções Subcutâneas , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Camundongos , Psoríase/metabolismo , Psoríase/terapia , Espécies Reativas de Oxigênio/metabolismo , Vitamina E/uso terapêutico
14.
Oncogene ; 41(8): 1166-1177, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35058597

RESUMO

BEST4 is a member of the bestrophin protein family that plays a critical role in human intestinal epithelial cells. However, its role and mechanism in colorectal cancer (CRC) remain largely elusive. Here, we investigated the role and clinical significance of BEST4 in CRC. Our results demonstrate that BEST4 expression is upregulated in clinical CRC samples and its high-level expression correlates with advanced TNM (tumor, lymph nodes, distant metastasis) stage, LNM (lymph node metastasis), and poor survival. Functional studies revealed that ectopic expression of BEST4 promoted CRC cell proliferation and metastasis, whereas the depletion of BEST4 had the opposite effect both in vitro and in vivo. Mechanistically, BEST4 binds to the p85α regulatory subunit of phosphatidylinositol-3-kinase (PI3K) and promotes p110 kinase activity; this leads to activation of Akt signaling and expression of MYC and CCND1, which are critical regulators of cell proliferation and metastasis. In clinical samples, the expression of BEST4 is positively associated with the expression of phosphorylated Akt, MYC and CCND1. Pharmacological inhibition of Akt activity markedly repressed BEST4-mediated Akt signaling and proliferation and metastasis of CRC cells. Importantly, the interaction between BEST4 and p85α was also enhanced by epidermal growth factor (EGF) in CRC cells. Therapeutically, BEST4 suppression effectively sensitized CRC cells to gefitinib treatment in vivo. Taken together, our findings indicate the oncogenic potential of BEST4 in colorectal carcinogenesis and metastasis by modulating BEST4/PI3K/Akt signaling, highlighting a potential strategy for CRC therapy.


Assuntos
Proteínas Proto-Oncogênicas c-akt
15.
Sci Total Environ ; 742: 140597, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-32629271

RESUMO

Polychlorinated biphenyls (PCBs) and halogen flame retardants (HFRs) are major pollutants in e-waste recycling area. High internal exposure levels of PCBs and HFRs are harmful to human thyroid hormone (TH) equilibrium. To examine their disrupting effects on TH, we conducted a study on children (n = 114) of an e-waste recycling and a control area in South China. Concentrations of PCBs, HFRs, and TH levels were determined in serum samples. TH related proteins and their corresponding gene were also monitored as markers of such disruption. Levels of these chemicals in the exposed group were much greater than those in the control group. Results of the linear regression and generalized additive model indicated the presence of close relationships between the internal exposure levels and the responses of TH related proteins, gene expression. More extensive exposure concentrations of these chemicals led to higher expression of iodothyronine deiodinase I and decreased the concentrations of thyroid-stimulating hormone, expression of TH receptor α, indicating the exertion of discrepant and even contrary influences on equilibrium of TH, and a compensation of these mechanisms may kept the homeostasis of TH. These results for children warrant further investigation on the health risks of PCBs and HFRs exposure in e-waste area.


Assuntos
Resíduo Eletrônico/análise , Retardadores de Chama , Bifenilos Policlorados/análise , Criança , China , Halogênios , Humanos , Proteínas , Reciclagem , Hormônios Tireóideos
16.
J Dig Dis ; 21(4): 205-214, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32223013

RESUMO

OBJECTIVE: To investigate histopathologic changes of muscularis mucosae (MM) and submucosa in the gastric cardia. METHODS: We performed a histopathology study of 50 distal esophagectomies with proximal gastrectomies for esophageal squamous cell carcinoma as the study (non-cancerous cardiac) group and 60 gastrectomies for early gastric cardiac carcinoma as the cancer group. The gastroesophageal junction was defined as the distal end of squamous epithelium, multilayered epithelium, or deep esophageal glands or ducts. Gastric cardia (n = 110) was defined as the presence of cardiac and cardio-oxyntic mucosae distal to the gastroesophageal junction. RESULTS: The average thickness of MM and submucosa in the cardia was 1.04 and 1.41 mm, respectively, which was significantly thicker than that in distal stomach (n = 34) (0.22 and 0.99 mm) or distal esophagus (n = 92) (0.60 and 1.15 mm). In the cardia, thickened MM displayed frayed muscle fibers (93.3%) with a significantly higher prevalence of entrapped glands, cysts, and lymphoid follicles than in the distal stomach or distal esophagus. In the submucosa fatty changes, cysts, and abnormal arteries were significantly more common in the cardia than in the distal stomach or distal esophagus. Compared with the study group, the cardia in the cancer group showed significantly thicker MM (average 1.31 vs 0.72 mm) and submucosa (average 1.61 vs 1.16 mm), more frequent frayed MM (93.3% vs 60.0%), prolapse-like changes (50.0% vs 2.0%), and cysts (26.7% vs 4.0%). CONCLUSION: MM and submucosa of the cardia were significantly thickened, especially in early gastric cardiac carcinomas.


Assuntos
Cárdia/patologia , Mucosa Esofágica/patologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Mucosa Gástrica/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia , Junção Esofagogástrica/patologia , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade
17.
Environ Pollut ; 254(Pt B): 112925, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31454572

RESUMO

Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and new flame retardants (NFRs) are known thyroid hormone (TH) disruptors, but their disrupting mechanisms in humans are not completely understood. In this study, we aimed to explore the disrupting mechanisms of the aforementioned chemicals via examining TH-regulated proteins and gene expression in human serum. Adult participants from an e-waste dismantling (exposed group) and a control region (control group) in South China provided blood samples for the research. Some compounds of PCBs, PBDEs, and NFRs showed strong binding affinity to the thyroid-stimulating hormone (TSH), thyroglobulin, thyroxine-binding globulin (TBG), gene expression of TH receptor α (TRα) and ß, and iodothyronine deiodinase I (ID1). The highly exposed individuals had lower levels of TBG, TSH, and expression of TRα, but higher expression of ID1 than those of the control group. The disruption of TH-regulated proteins and gene expression suggested the exertion of different and, at times, even contradictory effects on TH disruption. However, no statistically significant difference was found in the TH levels between the exposed and the control group, implying that the TH disruption induced by these chemicals depends on the combined influence of multiple mechanisms. Gene expression appears to be an effective approach for investigations of TH disruption and the potential health effects.


Assuntos
Resíduo Eletrônico/efeitos adversos , Retardadores de Chama/análise , Éteres Difenil Halogenados/sangue , Bifenilos Policlorados/sangue , Hormônios Tireóideos/sangue , Adulto , Idoso , China , Feminino , Retardadores de Chama/efeitos adversos , Expressão Gênica/efeitos dos fármacos , Éteres Difenil Halogenados/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Bifenilos Policlorados/efeitos adversos , Receptores dos Hormônios Tireóideos/genética , Receptores dos Hormônios Tireóideos/metabolismo , Tireotropina/sangue , Globulina de Ligação a Tiroxina/genética , Globulina de Ligação a Tiroxina/metabolismo
18.
Cancer Biol Ther ; 20(3): 240-246, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30252567

RESUMO

More than 90% of thyroid cancer belongs to the papillary and follicular thyroid carcinomas based on pathological subtypes. Papillary and follicular thyroid carcinoma are generally associated with a good prognosis. In contrast, other pathological subtypes such as poorly-differentiated and anaplastic thyroid carcinoma (PDTC and ATC) have a poor clinical outcome with a short life expectancy. To identify the genetic variations and biomarkers that may potentially distinguish the aggressive form of thyroid cancer, we performed a retrospective analysis of the formalin-fixed paraffin-embedded tumor samples from 50 patients who mainly displayed aggressive thyroid cancer using next-generation sequencing of 416 solid tumor-related genes. We adopted extensive bioinformatic analysis to vigorously remove germline single-nucleotide polymorphism and systematic sequencing errors, and report here that mutation in DNMT3A gene was significantly enriched in patients with PDTC or ATC.


Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Mutação , Carcinoma Anaplásico da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , DNA Metiltransferase 3A , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia
19.
J Dig Dis ; 19(10): 586-595, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30207084

RESUMO

OBJECTIVE: To investigate the risk factors of lymph node metastasis (LNM) in early gastric carcinoma (EGC) in a Chinese population. METHODS: The data were analyzed to determine risk factors of LNM. The patients' characteristics, the tumor's location, gross features, histological type, differentiation, invasive depth, lymphovascular invasion (LVI), perineural invasion and the numbers of lymph nodes retrieved and involved were statistically analyzed. RESULTS: A total of 734 patients with EGC were finally enrolled in the study, and LNM was present in 14.2% (104/734) of them. By univariate analysis, significant risk factors for LNM included depressed or excavated gross patterns, size ≥1.0 cm, SM2, moderate/poor differentiation, histological type of hepatoid or micropapillary adenocarcinoma, LVI, perineural invasion and tumor necrosis. By multivariate analysis, independent risk factors for LNM were size ≥3.0 cm (odds ratio [OR] 4.9), SM2 (OR 2.4), moderate (OR 3.6) and poor (OR 5.0) differentiation, LVI (OR 3.1) and tumor necrosis (OR 1.7). Early gastric cardiac carcinoma (OR 0.3) had a significantly lower risk than non-cardiac carcinoma. No LNM was identified in 67 EGC of <1.0 cm in size and without poor differentiation, in 142 intramucosal EGC cases of smaller than 2.0 cm and without poor differentiation, in 129 cases of well-differentiated EGC without deep SM2 submucosal invasion, or in 54 intramucosal EGC located in the gastric cardia. CONCLUSION: Independent risk factors for LNM in EGC include tumor size ≥3.0 cm, SM2 invasion, moderate/poor differentiation, LVI and tumor necrosis. Early cardiac carcinoma had a significantly lower risk of LNM than non-cardiac EGC.


Assuntos
Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Necrose , Invasividade Neoplásica , Fatores de Risco , Neoplasias Gástricas/cirurgia
20.
Chemosphere ; 202: 476-482, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29579682

RESUMO

As surrogates of polybrominated diphenyl ethers (PBDEs), new flame retardants (NFRs) include a series of chlorinated and brominated flame retardants. Though the NFRs are thought to induce similar thyroid hormone (TH) disrupting effects as PBDEs, few studies have focused on them. Given the increasing levels of NFRs in the environment, more in depth investigation of the potential TH disrupting effects of NFRs is warranted. This research involved a health survey to collect data and examine the associations between PBDEs, NFRs and TH. 174 school students lived near a petrochemical complex in South China participated in the survey, completing questionnaires and providing blood samples. Thirteen congeners of PBDEs, eight species of NFRs, TH and thyroid-stimulating hormone (TSH) were measured. The median levels of ΣPBDE (sum of thirteen congeners of PBDEs) and ΣNFR (sum of eight species of NFRs) for students were 140 and 240 ng g-1 lipid, respectively. Nonmonotonic relationships were observed between quartile levels of PBDEs, NFRs and corresponding TH. In contrast to ΣPBDE that was positively associated with triidothyrine (T3) level, ΣNFR was not statistically associated with TH. ΣPBDE + NFR (sum of thirteen congeners of PBDEs and eight species of NFRs) was significantly associated with T3 level.


Assuntos
Retardadores de Chama/análise , Éteres Difenil Halogenados/sangue , Hormônios Tireóideos/sangue , Criança , China , Retardadores de Chama/efeitos adversos , Humanos , Bifenil Polibromatos/sangue , Bifenilos Policlorados/sangue , Instituições Acadêmicas , Estudantes , Tireotropina/sangue
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