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1.
Molecules ; 26(19)2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34641597

RESUMO

Ubiquitous occurrences of phthalic acid esters (PAEs) or phthalates in a variety of consumer products have been demonstrated. Nevertheless, studies on their occurrence in various types of bottled drinks are limited. In this study, fifteen PAEs were analyzed in six categories of bottled drinks (n = 105) collected from the Chinese market, including mineral water, tea drinks, energy drinks, juice drinks, soft drinks, and beer. Among the 15 PAEs measured, DEHP was the most abundant phthalate with concentrations ranging from below the limit of quantification (LOQ) to 41,000 ng/L at a detection rate (DR) of 96%, followed by DIBP (DR: 88%) and DBP (DR: 84%) with respective concentration ranges of below LOQ to 16,000 and to 4900 ng/L. At least one PAE was detected in each drink sample, and the sum concentrations of 15 PAEs ranged from 770 to 48,004 ng/L (median: 6286 ng/L). Significant differences with respect to both PAE concentrations and composition profiles were observed between different types of bottled drinks. The median sum concentration of 15 PAEs in soft drinks was over five times higher than that detected in mineral water; different from other drink types. Besides DEHP, DBIP, and DBP, a high concentration of BMEP was also detected in a tea drink. The estimated daily dietary intake of phthalates (EDIdrink) through the consumption of bottled drinks was calculated based on the concentrations measured and the daily ingestion rates of bottled drink items. The EDIdrink values for DMP, DEP, DIBP, DBP, BMEP, DAP, BEEP, BBP, DCP, DHP, BMPP, BBEP, DEHP, DOP, and DNP through the consumption of bottled mineral water (based on mean concentrations) were 0.45, 0.33, 12.5, 3.67, 2.10, 0.06, 0.32, 0.16, 0.10, 0.09, 0.05, 0.81, 112, 0.13, and 0.20 ng/kg-bw/d, respectively, for Chinese adults. Overall, the EDIdrink values calculated for phthalates through the consumption of bottled drinks were below the oral reference doses suggested by the United States Environmental Protection Agency (U.S. EPA).


Assuntos
Bebidas/análise , Exposição Dietética/análise , Ácidos Ftálicos/análise , China , Cromatografia Gasosa , Ingestão de Líquidos , Disruptores Endócrinos/análise , Ésteres/análise , Humanos
2.
ACS Chem Neurosci ; 12(18): 3314-3322, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34445868

RESUMO

Luteolin is a flavone compound occurring in a variety of medicinal plants, which is reported to have neuroprotective properties. In this study, we aimed to explore the effects of luteolin in alleviating sevoflurane-induced neurotoxicity. GeneCards and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform were employed to screen luteolin, sevoflurane, and neurotoxicity-related genes. Subsequently, we isolated primary neurons from the hippocampus of 1-day-old C57BL/6J mice and tested for cytotoxicity after treatment of different concentrations of luteolin. Next, we measured the expression of apoptosis by flow cytometry and assessed inflammation-related factors, including heme oxygenase-1 expression detected by immunohistochemical staining and neuronal apoptosis. Finally, water maze, open field, and fear conditioning tests were conducted to observe the interaction between luteolin and sevoflurane in cognitive impairment of mice. Luteolin had the lowest cytotoxicity at concentrations of 30 or 60 µg/mL; we selected 30 µg/mL for drug administration experiments in vitro. Luteolin inhibited sevoflurane-induced neuronal apoptosis and inflammatory responses through the autophagic pathway and thus ameliorated sevoflurane-induced cognitive impairment in mice. Mechanistically, luteolin up-regulated heme oxygenase-1 expression, which activated the autophagy pathway in vitro. This was confirmed by subsequent histological experiments in mice and behavioral results showing rescue cognitive impairment. Our findings uncovered an inhibitory role of luteolin in sevoflurane-induced neuronal apoptosis and inflammatory response through activation of autophagy arising from up-regulation of heme oxygenase-1, thereby alleviating sevoflurane-induced cognitive impairment in mice.


Assuntos
Heme Oxigenase-1 , Luteolina , Animais , Apoptose , Autofagia , Hipocampo , Luteolina/farmacologia , Aprendizagem em Labirinto , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos C57BL , Sevoflurano/toxicidade
3.
Artigo em Inglês | MEDLINE | ID: mdl-33986813

RESUMO

Objective: The randomized controlled clinical trial aims to investigate the clinical efficacy of moxibustion for breast cancer patients with chemotherapy-induced myelosuppression (CIM) during adjuvant chemotherapy. Methods: Surgically resected breast cancer patients were randomly divided into the moxibustion group (MOX; n = 48) and control group (CON; n = 44). Routine adjuvant chemotherapy (every 21 days, 4-8 cycles) and supportive recombinant human granulocyte colony-stimulating factor were given to both groups, while MOX received an additional moxibustion treatment (once daily after each cycle of chemotherapy). Primary endpoints included the grade of myelosuppression in terms of white blood cell (WBC) and absolute neutrophil count (ANC) and the incidence of myelosuppression-related serious adverse events (SAEs). Other measures included treatment compliance, adverse events (AEs), and survival. Results: WBC counts were generally higher in MOX and were dramatically higher than those in CON at the 7th course of chemotherapy (P=0.008), while grade 1 ANC reduction was dramatically lower than that in CON at the 7thcourse of chemotherapy (P=0.006). These effects were particularly significant in patients receiving anthracycline-taxane combination regimens. Moreover, MOX had fewer febrile neutropenia than CON (P=0.051). MOX demonstrated a lower incidence of grade 3-4 myelosuppression (P < 0.05). AEs including grade 2-3 severe nausea, various kinds of pains, and vertigo occurred less frequently in MOX (P < 0.05). No difference in survival was observed between the two groups (P > 0.05). Conclusion: Moxibustion is effective for treating CIM in breast cancer patients during adjuvant chemotherapy, especially for patients receiving high-dose, long-term, and combined chemotherapy regimens. Moxibustion can reduce the incidence of myelosuppression-related SAE and improve the compliance and safety of chemotherapy in breast cancer.

4.
BMC Cancer ; 21(1): 67, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446144

RESUMO

BACKGROUND: The role of nicotinamide N-methyltransferase (NNMT) in ovarian cancer is still elusive. Our aim is to explore the expression of NNMT in ovarian cancer and to assess its association with patient prognosis and treatment response. METHODS: We first analyzed the differential expression of NNMT among fallopian tube epithelium, primary ovarian cancers, metastatic ovarian cancers, and recurrent ovarian cancers using Gene Expression Ominus (GEO) database (GSE10971, GSE30587, GSE44104 and TCGA datasets). Then, we assessed the association of NNMT expression with clinical and molecular parameters using CSIOVDB database and GSE28739 dataset. Next, we evaluate the association of NNMT expression with the prognosis of ovarian cancer patients in both GSE9891 dataset and TCGA dataset. Finally, GSE140082 dataset was used to explore the association of NNMT expression with bevacizumab response. RESULTS: NNMT expression was significantly elevated in lymphovascular space invasion (LVSI)-positive ovarian cancers compared with that in LVSI-negative ovarian cancers (TCGA dataset, P < 0.05), Moreover, increased expression of NNMT was associated with increased tumor stage, grade, and mesenchymal molecular subtype (CSIOVDB database). Survival analysis indicated that increased expression of NNMT was associated with a reduced OS in both GSE9891 dataset (HR: 2.28, 95%CI: 1.51-3.43, Log-rank P < 0.001) and TCGA dataset (HR: 1.55, 95%CI: 1.02-2.36, Log-rank P = 0.039). Multivariate analysis further confirmed the negative impact of NNMT expression on OS in ovarian cancer patients in those two datasets. Furthermore, the NNMT-related nomogram showed that NNMT shared a larger contribution to OS, compared with debulking status. More interestingly, bevacizumab conferred significant improvements in OS for patients with low NNMT expression (HR: 0.56, 95%CI: 0.31-0.99, Log-rank P = 0.049). In contrast, patients with high NNMT expression didn't benefit from bevacizumab treatment significantly (HR: 0.85, 95%CI: 0.48-1.49, Log-rank P = 0.561). NNMT expression was positively correlated with the expression of genes, LDHA and PGAM1, involved in Warburg effect. CONCLUSIONS: In conclusion, NNMT expression is associated with the aggressive behavior of ovarian cancer, correlates with a poor prognosis, and is predictive of sensitivity to bevacizumab treatment.


Assuntos
Bevacizumab/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias das Tubas Uterinas/tratamento farmacológico , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Nicotinamida N-Metiltransferase/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias das Tubas Uterinas/metabolismo , Neoplasias das Tubas Uterinas/secundário , Feminino , Seguimentos , Humanos , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Nicotinamida N-Metiltransferase/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Prognóstico , Taxa de Sobrevida
5.
Artigo em Inglês | MEDLINE | ID: mdl-33493421

RESUMO

Background: Triple-negative breast cancer (TNBC) is the most serious subtype of breast cancer (BC) and has been a great health threat to females. Although chemotherapeutic agent contributes a lot to TNBC treatment, drug resistance has been a great obstacle for chemotherapies. Ursolic acid (UA), a pentacyclic triterpenoid compound, was reported to reverse paclitaxel resistance in BC. However, whether UA could affect the resistance of TNBC cells to other drugs such as doxorubicin (DOX) remains to be discovered. Materials and Methods: MTT assay, EdU assay, colony formation assay, and flow cytometry analysis were implemented to detect the viability, proliferation, and apoptosis of DOX-resistant MDA-MB-468 and MDA-MB-436 cells with or without UA treatment. Mechanism assays including RIP, RNA pull-down, and luciferase reporter assays verified the interaction between RNAs. Results: UA treatment hindered the growth and mitigated the DOX resistance of DOX-resistant MDA-MB-468 and MDA-MB-436 cells. Mechanistically, multidrug resistance-associated protein 1 (ABCC1) expression was downregulated by UA treatment. MiR-186-5p was verified to target ABCC1. Further, UA-inhibited ZEB1-AS1 (zinc finger E-box binding homeobox 1 antisense RNA 1) was verified as a competitive endogenous RNA (ceRNA) to upregulate ABCC1 through sponging miR-186-5p. Importantly, UA treatment impaired the malignant phenotypes of DOX-resistant MDA-MB-468 and MDA-MB-436 cells through ZEB1-AS1/ABCC1 axis. Conclusion: UA promotes TNBC cell sensitivity to DOX through inactivating ZEB1-AS1/miR-186-5p/ABCC1 signaling.

6.
Mol Med Rep ; 22(6): 5145-5154, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33174608

RESUMO

Tripartite motif­containing (TRIM) 14 is a protein of the TRIM family. Studies have indicated that TRIM14 may be used as an oncogene in tumor cells, such as osteosarcoma, non­small cell lung cancer and breast cancer through different pathways. However, the functions of TRIM14 in cervical cancer cells remain unclear. Therefore, this study aimed to investigate the functions of TRIM14 in cervical cancer cells and its underlying mechanism. Caski cells stably expressing TRIM14 and SiHa, and HeLa cells stably expressing TRIM14 short hairpin RNA were constructed by lentivirus­mediated overexpression or knockdown systems. The effects of TRIM14 on proliferation and apoptosis of cervical cancer cells were detected by Cell Counting Kit­8 (CCK­8) assay and flow cytometry, respectively. In addition, reverse transcription­quantitative (RT­q) PCR and western blotting were used to investigate the expression levels of TRIM14 and of signaling pathway marker protein including P21, caspase­3, cleaved caspase­3, Akt and phosphorylated Akt. The results of RT­qPCR and western blotting revealed that TRIM14 was highly expressed in human cervical cancer tissues and cell lines compared with adjacent normal tissues and normal cervical epithelial cells. TRIM14 also regulated cell proliferation and apoptosis of human SiHa, HeLa and Caski cervical cancer cell lines through the Akt signaling pathway. Additionally, TRIM14 protein levels were related to the clinical and pathological features of cervical cancer. CCK­8 assay and flow cytometry demonstrated that TRIM14 expression could promote cervical cancer cell proliferation and autophagy suppression. Taken together, TRIM14­induced cell proliferation and apoptosis inhibition may by evoked by the activation of the Akt pathway. This study demonstrated the role of TRIM14 in cervical cancer, and reveals its mechanism of action as a potential therapeutic target for cervical cancer.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Adulto , Idoso , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Colo do Útero/patologia , China , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células HeLa , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Pessoa de Meia-Idade , Oncogenes/genética , Osteossarcoma/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/genética , Proteínas com Motivo Tripartido/genética
7.
Biosci Rep ; 40(12)2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33146718

RESUMO

MicroRNAs (miRNAs) regulate the progression of human malignancy by targeting oncogenes or tumor suppressors, which are 12 promising targets for cancer treatment. Increasing evidence has suggested the aberrant expression and tumor-suppressive function of miR-1298 in cancers, however, the regulatory mechanism of miR-1298 in breast cancer (BC) remains unclear. Here, our findings showed that miR-1298 was down-regulated in BC tissues and cell lines. Lower level of miR-1298 was significantly correlated with the advanced progression of BC patients. Experimental study showed that overexpression of miR-1298 inhibited the proliferation, induced apoptosis and cell cycle arrest in BC cells. The in vivo xenograft mice model showed that highly expressed miR-1298 significantly reduced the tumor growth and metastasis. Further mechanism analysis revealed that miR-1298 bound the 3'-untranslated region (UTR) of a disintegrin and metalloproteinase 9 domain (ADAM9) and suppressed the expression of ADAM9 in BC cells. ADAM9 was overexpressed in BC tissues and inversely correlated with miR-1298. Down-regulation of ADAM9 induced apoptosis and cell cycle arrest of BC cells. Moreover, ectopic expression of ADAM9 by transiently transfecting with vector encoding the full coding sequence of ADAM9 attenuated the inhibitory effects of miR-1298 on the proliferation and cell cycle progression of BC cells. Collectively, our results illustrated that miR-1298 played a suppressive role in regulating the phenotype of BC cells through directly repressing ADAM9, suggesting the potential application of miR-1298 in the therapy of BC.


Assuntos
Proteínas ADAM/metabolismo , Neoplasias da Mama/enzimologia , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Proteínas ADAM/genética , Adulto , Idoso , Animais , Apoptose , Sítios de Ligação , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proliferação de Células , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Proteínas de Membrana/genética , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Transdução de Sinais , Carga Tumoral
8.
Trials ; 21(1): 844, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046128

RESUMO

BACKGROUND: Traditional Chinese medicine (TCM) has a long history of use in breast cancer, but lacking systematic evidence to support its clinical benefits. In this study, we evaluated the prophylactic and therapeutic effects of moxibustion combined with decoctions for treating chemotherapy-induced myelosuppression (CIM) in early-stage breast cancer patients. METHODS: This is a randomized controlled clinical trial single-blinded for TCM decoction but not moxibustion. Patients are equally divided into the control group without decoction and moxibustion treatment (control), the decoction+moxibustion group (MD), and the placebo+moxibustion group (MP), according to the following stratification factors: age (below 40s, 40s, 50s, and 60s or above), chemotherapy regimen (anthracyclines, taxanes, anthracyclines+taxane, and others), and chemotherapy strategy (adjuvant and neoadjuvant). The TCM decoction is Wenshen Shengbai Decoction. The anticipated sample size is 462 cases (154 cases in each group). All participants are expected to treat with chemotherapy and recombinant human granulocyte colony-stimulating factor (rhG-CSF). The primary outcomes include the proportion of patients with relief of leukopenia and/or neutropenia, the myelosuppression-associated serious adverse event including grade 3-4 leukopenia and/or neutropenia, and febrile neutropenia, and the dose of rhG-CSF. The secondary outcomes include chemotherapy adherence, stratified analysis, adverse reactions, quality of life by EORTC Breast-Cancer-Specific Quality of Life Questionnaire including EORTC QLQ-C30 (V3.0) and QLQ-BR23, TCM Constitution, and 3-year disease-free survival and overall survival. Baseline information including age, surgical approach, chemotherapy regimen and strategy, pathological stage, and molecular subtype will be recorded. DISCUSSION: This will be the first randomized controlled trial to evaluate the efficacy of moxibustion combined with TCM decoction in treating CIM in early-stage breast cancer patients, aiming to standardize the TCM decoction and moxibustion method, thus providing evidence for its clinical benefit. TRIAL REGISTRATION: chictr.org.cn ChiCTR-INR-16009557 . Registered on 23 October 2016.


Assuntos
Neoplasias da Mama , Moxibustão , Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Medicina Tradicional Chinesa , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Eur J Obstet Gynecol Reprod Biol ; 251: 162-166, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32505789

RESUMO

OBJECTIVES: To evaluate the outcomes and related factors of gestational trophoblastic neoplasia (GTN) with lung metastasis in comparison with GTN without metastasis. STUDY DESIGN: GTN is a spectrum of diseases arising from trophoblastic cells, and treatment outcome is promising because of its high sensitivity to chemotherapy. Lung metastasis is not usually considered to be an adverse prognostic factor in the evaluation and treatment of GTN. The clinical records of 48 GTN patients with lung metastasis and 162 GTN patients without metastasis were reviewed and analysed retrospectively from 2003 to 2013. Data were compared between patients with and without metastasis. RESULTS: Twenty-five percent of GTN patients with lung metastasis presented with pre-treatment serum human chorionic gonadotropin ≥105 mIU/mL, which was significantly higher compared with GTN patients without metastasis (9.3 %, p < 0.01). Regarding the International Federation of Gynecology and Obstetrics (FIGO) score, 39.6 % of patients with lung metastasis were in the high-risk group (FIGO score ≥ 7), compared with 13.6 % of patients without metastasis (p < 0.01). However, on multi-variate analysis, only a FIGO score ≥7 was associated with lung metastasis. The relapse rate of GTN patients with lung metastasis was significantly higher than that of those without metastasis (8.3 % vs 0.6 %, p < 0.05). In the patients who relapsed, non-postmolar GTN, high-risk GTN and first-line chemoresistance were observed more frequently compared with the patients who did not relapse (p < 0.05). CONCLUSION: GTN patients with lung metastasis appear to have increased risk of relapse compared with GTN patients without metastasis. To overcome this, there is a need to consider adjustment of the FIGO scoring system to enable GTN patients with lung metastasis to receive more intensive chemotherapy.


Assuntos
Doença Trofoblástica Gestacional , Neoplasias Pulmonares , Gonadotropina Coriônica , Feminino , Doença Trofoblástica Gestacional/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia , Gravidez , Estudos Retrospectivos
12.
J Photochem Photobiol B ; 202: 111676, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31837583

RESUMO

Wounds origins serious complications of lives of human beings which may leads to death. The important issue for the problem is infection during wound care management which delays wound healing process. These kinds of infections may be caused by the overuse or misuse of antibiotics, antidotes, usage of new drugs, not properly sterilized surgical instruments, not appropriate for pH level and imperfect wound dressing etc. during or after surgery. Hence in this report, antimicrobial action of pH responsive TA/KA composited hydrogel crosslinked with GO-QDs (TA/KA-GOQDs) using citric acid as cross-linker has been reported by demonstrating in-vitro and in-vivo studies for wound care management. The prepared samples of GOQDs, TA/KA hydrogel and TA/KA-GOQDs were characterized using FT-IR, XRD, SEM and TEM techniques. pH responsive hydrogel property of TA/KA was evaluated by swelling studies. In-vitro antibacterial studies was carried out by direct contact test method. Further, the prepared samples were tested in a wound healing model of rate with the wound of size 1.5 cm2 for in-vivo studies. After 16 days of treatment, the prepared samples for wound healing causes 100% wound areas closure. Histological observations were made by MT and HE staining process which proves keratinocytes proliferation by biocompatible and biocomposited TA/KA-GOQDs. The pH responsive TA/KA-GOQDs proved as efficient wound healing agent by faster keratinocytes proliferation within a compact period.


Assuntos
Materiais Biocompatíveis/farmacologia , Grafite/química , Hidrogéis/química , Queratinas/química , Pontos Quânticos/química , Cicatrização/efeitos dos fármacos , Animais , Materiais Biocompatíveis/química , Proliferação de Células/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Queratinócitos/citologia , Queratinócitos/metabolismo , Ratos , Pele/patologia , Staphylococcus aureus/efeitos dos fármacos
13.
Environ Sci Pollut Res Int ; 27(6): 6269-6277, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31865567

RESUMO

Dechlorane plus (DP) is a chlorinated flame retardant with high production volume (HPV) and is widely used in our daily necessities. In the present study, a laboratory-scale microcosm was built up to simulate the uptake, depuration, bioaccumulation, and stereoselective enrichment of DP in a lower concentration and equilibration condition. Common carp (Cyprinus carpio) were used for 32 days exposure and 32 days depuration. The concentration ratios of syn-DP to total DP (fsyn values) in fish examined were lower than that in commercial products. Rate constants of uptake (kS) and elimination (ke) for the syn- and anti-DP were calculated using a first-order kinetic model. The uptake rate constants of syn- and anti-DP were 0.63 and 0.89 day-1, respectively. The depuration rate constants of syn-DP (0.11 day-1) were similar to anti-DP (0.096 day-1), suggesting that anti-DP is absorbed faster than syn-DP by common carp. The estimated bioconcentration factors for both syn-DP (5700 L/kg) and anti-DP (9300 L/kg) were higher than the bioconcentration hazard criteria outlined in the Stockholm Convention, suggesting the bioconcentration potential to aquatic organisms for DP.


Assuntos
Carpas/metabolismo , Monitoramento Ambiental , Hidrocarbonetos Clorados/metabolismo , Compostos Policíclicos/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Bioacumulação , Retardadores de Chama
14.
J Ovarian Res ; 12(1): 47, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113446

RESUMO

OBJECTIVE: Our aim is to analyzed the expression pattern of sirtuin(SIRT) superfamily and evaluated their prognostic values in serous ovarian cancer patients. METHODS: We first analyzed the differential expression of SIRT members among fallopian tube epithelium (FTE), primary serous ovarian cancers/tubal cancers (PSOCs/PSTCs), and omental metastases using GSE10971 and GSE30587 datasets. The prognostic values of SIRT members were evaluated using TCGA and GSE9891 dataset. RESULTS: SIRT3 and SIRT5 expression were significantly decreased and increased in PSOCs/PSTCs compared with that in normal counterparts, respectively. SIRT6 and SIRT7 were overexpressed in ometal metastases compared with corresponding primary counterparts. With respect to recurrence free survival, however, SIRT7 overexpression was correlated with better prognosis. A similar trend was observed by multivariable analysis. Regarding overall survival (OS), increased expression of SIRT3, SIRT5, and SIRT7 were associated with better survival by univariable analysis. Subsequent multivariable analysis showed that SIRT3 remained an independent favorable prognostic factor for OS. The SIRT3-related nomogram illustrated age at initial diagnosis as sharing the largest contribution to OS, followed by SIRT3 expression and FIGO stage. The C-index for OS prediction was 0.65 (95%CI, 0.61-0.69) in training cohort (TCGA dataset) and 0.65 (95%CI, 0.59-0.71) in validation cohort (GSE9891 dataset), respectively. The calibration plots showed optimal agreement between the prediction by SIRT3-related nomogram and actual observation for 1-, 3-, and 5-year OS probability. CONCLUSION: In conclusion, SIRT3 was an independent favorable prognostic factor for OS in serous ovarian cancer, and added prognostic value to the traditional clinicopathological factors used to evaluate patients' prognosis.


Assuntos
Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/mortalidade , Neoplasias das Tubas Uterinas/mortalidade , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Sirtuína 3/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Cistadenocarcinoma Seroso/patologia , Intervalo Livre de Doença , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/patologia , Feminino , Expressão Gênica , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Estadiamento de Neoplasias , Nomogramas , Neoplasias Ovarianas/patologia , Prognóstico , Sirtuínas/genética , Taxa de Sobrevida
15.
Curr Mol Med ; 19(2): 147-155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30854965

RESUMO

PURPOSE: Breast cancer is the most prevalent malignancy and the leading cause of death among women. Triple-negative breast cancer (TNBC) is a subtype of breast cancer and shows a distinctly aggressive nature with higher rates of relapse and shorter overall survival in the metastatic setting compared to other subtypes of breast cancer. This study aimed to assess the effect of KIF15 on various clinicopathological characteristics, survival analysis, and cell proliferation in triple-negative breast cancer, which has not been reported to our knowledge. METHODS: A total of 165 patients with triple-negative breast cancer were enrolled and clinical data were obtained, Mann-Whitney U analysis was performed to assess the correlation between the expression of KIF15 and clinical pathological characteristics of TNBC patients. Survival analysis was performed by Kaplan-Meier analysis and Log-rank test. The expression levels of KIF15 in cancer tissues and adjacent tissues were evaluated via Sign test. Lentivirus was used to down-regulate the expression of KIF15 in TNBC cells. The cell proliferation, colony formation capacity and apoptosis were examined by MTT, Giemsa staining and flow cytometry assay, respectively. RESULTS: Our results showed that, among the 165 TNBC patients, the expression of KIF15 was positive correlation with clinicopathological features of TNBC. In addition, KIF15 low-expression group showed higher disease-free survival than KIF15 highexpression group and univariate analysis showed that KIF15 high-expression group appeared higher mortality than KIF low-expression group (P ≤ 0.05). Meanwhile, the expression levels of KIF15 in cancer tissue notably up-regulated in comparison with adjacent tissue. In vitro, knockdown of KIF15 significantly promoted cell apoptosis and suppressed cell proliferation and colony formation of TNBC cells. CONCLUSION: By utilizing survival analysis, we found that high-expression of KIF15 in the TNBC samples were associated with poorer overall survival, while the anti-tumor effect of KIF15 knockdown was also confirmed at the cellular level in vitro. Taken together, KIF15 can be applied as a potential diagnostic and therapeutic target in TNBC.


Assuntos
Biomarcadores Tumorais/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Cinesina/antagonistas & inibidores , RNA Interferente Pequeno/genética , Neoplasias de Mama Triplo Negativas/patologia , Apoptose , Biomarcadores Tumorais/genética , Feminino , Seguimentos , Humanos , Técnicas In Vitro , Cinesina/genética , Cinesina/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Células Tumorais Cultivadas
16.
Arch Environ Contam Toxicol ; 76(3): 496-507, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30259079

RESUMO

Despite the high production volume and widespread use of methyl siloxanes, limited studies have been conducted to investigate the bioconcentration, biomagnification, and trophic magnification potentials of these substances. In the present study, bioconcentration factors (BCFs) of methyl siloxanes were determined with common carp exposed at environmental relevant levels for 32 days. BCF of octamethylcyclotetrasiloxane (D4) was estimated as 6197 L/Kg, indicating strong bioconcentration potential in the common carp. To assess the food chain transfer of methyl siloxanes, 12 aquatic invertebrates and vertebrates species were collected from a food web in Shuangtaizi estuary in northeastern China and concentrations of methyl siloxanes in these species were determined with gas chromatography mass spectrometry. Trophic magnification factors (TMFs) of decamethylcyclopentasiloxane (D5), dodecamethylcyclohexasiloxane (D6), and linear siloxanes (L7-10) were significantly greater than 1 in one food chain selected, which suggest trophic magnification potentials of these methyl siloxanes. Biomagnification factors of D4-D6 and L7-L10 from planktons to Japanese snapping shrimp were greater than 1, indicating biomagnification potentials of these methyl siloxanes from the prey to predator. This is the first study to investigate the bioaccumulation behaviors of methyl siloxanes by coupling BCF and BMF with TMF.


Assuntos
Carpas/metabolismo , Monitoramento Ambiental/métodos , Siloxanas/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , China , Estuários , Cadeia Alimentar
17.
J Physiol Anthropol ; 37(1): 5, 2018 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-29454386

RESUMO

BACKGROUND: The effects of acute hypoxia at high altitude on the telomere length of the cells in the heart and lung tissues remain unclear. This study aimed to investigate the change in telomere length of rat heart and lung tissue cells in response to acute exposure to severe hypoxia and its role in hypoxia-induced damage to heart and lung tissues. METHODS: Forty male Wistar rats (6-week old) were randomized into control group (n = 10) and hypoxia group (n = 30). Rats in control group were kept at an altitude of 1500 m, while rats in hypoxia group were exposed to simulated hypoxia with an altitude of 5000 m in a low-pressure oxygen chamber for 1, 3, and 7 days (n = 10). The left ventricular and right middle lobe tissues of each rat were collected for measurement of telomere length and reactive oxygen species (ROS) content, and the mRNA and protein levels of telomerase reverse transcriptase (TERT), hypoxia-inducible factor1α (HIF-1α), and hypoxia-inducible factor1α (HIF-2α). RESULTS: Increased exposure to hypoxia damaged rat heart and lung tissue cells and increased ROS production and telomere length. The mRNA and protein levels of TERT and HIF-1α were significantly higher in rats exposed to hypoxia and increased with prolonged exposure; mRNA and protein levels of HIF-2α increased only in rats exposed to hypoxia for 7 days. TERT was positively correlated with telomere length and the levels of HIF-1α but not HIF-2α. CONCLUSIONS: Acute exposure to severe hypoxia causes damage to heart and lung tissues due to the production of ROS but promotes telomere length and adaptive response by upregulating TERT and HIF-1α, which protect heart and lung tissue cells from fatal damage.


Assuntos
Coração/fisiologia , Hipóxia/fisiopatologia , Pulmão/fisiologia , Telômero/fisiologia , Altitude , Animais , Translocador Nuclear Receptor Aril Hidrocarboneto/análise , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/análise , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Pulmão/citologia , Pulmão/patologia , Masculino , Miocárdio/citologia , Miocárdio/patologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Telomerase/análise , Telomerase/metabolismo
18.
Cancer Cell Int ; 17: 80, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28912668

RESUMO

PURPOSE: Epithelial-mesenchymal transition (EMT), TP53, and Podoplanin have been implicated in the tumorigenesis and metastasis of human cancers. Nevertheless, the clinical significance of these markers in cancer patients is still not clear. In this study, we sought to determine the prognostic values of Vimentin, TP53, and Podoplanin in patients with cervical cancer. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were performed to determine the messenger RNA and protein expression levels of Vimentin, TP53, and Podoplanin, respectively, in cervical squamous cell carcinoma and adjacent normal cervical tissues. Additionally, the expression levels of Podoplanin were also measured in 130 cervical cancer patients (FIGO stages Ib1-IIa2) using immunohistochemistry (IHC) staining. RESULTS: The mRNA expression levels of Vimentin, TP53, and Podoplanin were considerably elevated in cervical cancer tissues, compared with those in the adjacent normal cervical tissues. Additionally, the protein expression levels of Vimentin were closely correlated with the age of onset (P = 0.007), lymph node metastasis (P = 0.007), lymphatic invasion (P = 0.024), disease recurrence (P < 0.001), and the clinical prognosis of patients with cervical cancer (P < 0.001). Our multivariate analysis also suggests that Vimentin is an independent marker for survival in cervical cancer patients. Furthermore, the expression levels of Vimentin are negatively correlated with the proliferation marker Ki67 expression. CONCLUSIONS: Our data show that Vimentin can serve as an independent prognostic marker for cervical cancer patients with primary surgery. Registration number ChiCTR-TRC-06000236 Registered 15 December 2006.

19.
Environ Sci Technol ; 51(2): 780-789, 2017 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-27959523

RESUMO

Despite the widespread use of parabens in a range of consumer products, little is known about bioaccumulation of these chemicals in aquatic environments. In this study, six parabens and four of their common metabolites were measured in abiotic (water, sediment) and biotic (fish including sharks, invertebrates, plants) samples collected from a subtropical marine food web in coastal Florida. Methyl paraben (MeP) was found in all abiotic (100%) and a majority of biotic (87%) samples. 4-Hydroxy benzoic acid (4-HB) was the most abundant metabolite, found in 97% of biotic and all abiotic samples analyzed. The food chain accumulation of MeP and 4-HB was investigated for this food web. The trophic magnification factor (TMF) of MeP was estimated to be 1.83, which suggests considerable bioaccumulation and biomagnification of this compound in the marine food web. In contrast, a low TMF value was found for 4-HB (0.30), indicating that this compound is metabolized and excreted along the food web. This is the first study to document the widespread occurrence of parabens and their metabolites in fish, invertebrates, seagrasses, marine macroalgae, mangroves, seawater, and ocean sediments and to elucidate biomagnification potential of MeP in a marine food web.


Assuntos
Cadeia Alimentar , Parabenos/metabolismo , Animais , Monitoramento Ambiental , Peixes/metabolismo , Invertebrados/metabolismo , Poluentes Químicos da Água
20.
Int Immunopharmacol ; 42: 195-202, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27930970

RESUMO

BACKGROUND: Astragaloside IV (AS-IV), the major active triterpenoid in Radix Astragali, has shown anti-tumorigenic properties in certain cancers; however, its role in breast cancer remains unclear. The present study investigated the effects of AS-IV on breast cancer in vitro and in vivo and examined the underlying mechanisms. METHODS: The effects of AS-IV on MDA-MB-231 cell proliferation, migration, invasion and metastasis were investigated by MTT and Transwell assays, and western blotting. In addition, an orthotopic mouse tumor model was established for in vivo experiments. RESULTS: AS-IV inhibited the viability and invasive potential of MDA-MB-231 breast cancer cells, suppressed the activation of the mitogen activated protein kinase (MAPK) family members ERK1/2 and JNK, and downregulated matrix metalloproteases (MMP)-2 and -9. The effects of AS-IV were mediated by the downregulation of Vav3, a guanine nucleotide exchange factor, leading to decreased levels of activated Rac1, a Rho family GTPase. Vav3 overexpression promoted cell proliferation and invasion in vitro, whereas Vav3 silencing had the opposite effects. AS-IV suppressed orthotopic breast tumor growth and metastasis to the lungs, whereas ectopic expression of Vav3 reversed the inhibitory effect of AS-IV on cell viability, invasiveness, MAPK signaling and MMP expression. CONCLUSION: The present results provide a mechanistic explanation for the antitumor effects of AS-IV and suggest its potential in the treatment of metastatic breast cancer.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células , Medicamentos de Ervas Chinesas , Proteínas Proto-Oncogênicas c-vav/metabolismo , Saponinas/farmacologia , Triterpenos/farmacologia , Proteínas rac1 de Ligação ao GTP/metabolismo , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular , Feminino , Humanos , Camundongos , Camundongos Nus , Proteínas Proto-Oncogênicas c-vav/genética , RNA Interferente Pequeno/genética , Transdução de Sinais/efeitos dos fármacos , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
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