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1.
Oncol Rep ; 46(3)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34278491

RESUMO

Serine proteinase inhibitor B9 (serpin B9) is a member of the serine protease inhibitor superfamily, which is widely found in animals, plants and microorganisms. Serpin B9 has been reported to protect cells from the immune­killing effect of granzyme B (GrB) released by lymphocytes. In recent years, an increasing number of studies have indicated that serpin B9 is involved in tumour apoptosis, immune evasion, tumorigenesis, progression, metastasis, drug resistance and even in maintaining the stemness of cancer stem cells (CSCs). Moreover, according to clinical studies, serpin B9 has been demonstrated to be significantly associated with the development of precancerous lesions, a poor prognosis and ineffective therapies, suggesting that serpin B9 may be a potential target for cancer treatment and an indicator of cancer diagnosis; thus, it has begun to attract increased attention from scholars. The present review concisely described the structure and biological functions of the serpin superfamily and serpin B9. In addition, related research on serpins in cancer is discussed in order to provide a comprehensive understanding of the role of serpin B9 in cancer, as well as its clinical significance for cancer diagnosis and prognosis.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias/metabolismo , Inibidores de Serina Proteinase/fisiologia , Serpinas/metabolismo , Serpinas/fisiologia , Animais , Antineoplásicos/farmacologia , Apoptose , Granzimas/metabolismo , Humanos , Sistema Imunitário , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Metástase Neoplásica , Neoplasias/imunologia , Neoplasias/terapia , Células-Tronco Neoplásicas/citologia , Prognóstico
2.
Phytother Res ; 35(8): 4401-4410, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33979464

RESUMO

Xiyanping (XYP) is a Chinese herbal medicine used in the clinic to treat respiratory infection and pneumonia. Recent evidence identified XYP as a potential inhibitor of severe acute respiratory syndrome coronavirus 2, implying XYP as a possible treatment for the coronavirus disease 2019 (COVID-19). Here, we conducted a prospective, multicenter, open-label and randomized controlled trial to evaluate the safety and effectiveness of XYP injection in patients with mild to moderate COVID-19. We consecutively recruited 130 COVID-19 patients with mild to moderate symptoms from five study sites, and randomized them in 1:1 ratio to receive XYP injection in combination with standard therapy or receive standard supportive therapy alone. We found that XYP injection significantly reduced the time to cough relief, fever resolution and virus clearance. Less patients receiving XYP injection experienced disease progression to the severe stage during the treatment process. No severe adverse events were reported during the study. Taken together, XYP injection is safe and effective in improving the recovery of patients with mild to moderate COVID-19. However, further studies are warranted to evaluate the efficacy of XYP in an expanded cohort comprising COVID-19 patients at different disease stages.


Assuntos
COVID-19 , Medicamentos de Ervas Chinesas/uso terapêutico , Adulto , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
3.
Oncol Rep ; 45(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33760175

RESUMO

Hypoxia is a common phenomenon during tumorigenesis and tumour development. In recent years, studies have found that hypoxia­inducible factor (HIF)­2α, also referred to as endothelial PAS domain protein­1, plays an important role in tumours. HIF­2α is an important oncogene and a critical prognostic indicator in non­small cell lung cancer. However, no unified conclusion can be drawn concerning HIF­2α and small cell lung cancer, since few studies to date have focused on their association. An increasing number of studies have confirmed that HIF­2α is involved in tumorigenesis, cell proliferation, angiogenesis, metastasis, drug resistance and radiotherapy failure in lung cancer. Of note, HIF­2α plays a crucial role in lung cancer to maintain cancer cell stemness. Based on the importance of HIF­2α in lung cancer, HIF­2α­targeted therapy has been attracting increasing attention. Although this strategy currently appears to be promising in vitro, it has never been assessed as a therapy for lung cancer. The aim of the present review was to summarize the contribution of HIF­2α to various aspects of lung cancer, as well as its potential as targeted therapy.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pulmonares/genética , Neovascularização Patológica/genética , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Carcinogênese/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Quimiorradioterapia/métodos , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Terapia de Alvo Molecular/métodos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Prognóstico , Intervalo Livre de Progressão , Tolerância a Radiação/genética
4.
Mol Biol Rep ; 47(11): 8407-8417, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33068229

RESUMO

Blastomere loss is a common issue during frozen-thawed embryo transfer (FET). Our previous study showed that blastomere loss was associated with an increased risk of small-for-gestational-age (SGA) neonates. The present study assessed the impact of blastomere loss during cryopreservation by comparing the mRNA profiles of umbilical cord blood of FET offspring from the prospective cohort study. Umbilical cord blood samples were collected from 48 neonates, including 12 from the loss group, 11 from the intact group, and 25 from the matched spontaneous pregnancy group. RNA-seq technology was used to compare the global gene expression profiles of the lymphocytes. Then, we used TopHat software to map the reads and quantitative real-time PCR to validate some important differentially expressed genes (DEGs). We identified 92 DEGs between the loss group and the spontaneous pregnancy group, including IGF2 and H19. Ingenuity Pathway Analysis (IPA) showed that the DEGs were most affected in the blastomere loss group. Downstream analysis also predicted the activation of organismal death pathways. In conclusions, our pilot study sheds light on the mechanism underlying how human blastomere loss may affect offspring at the gene expression level. These conclusions are, however, only suggestive, as the current study is based on a very limited sample size and type or nature of biological samples. Additional studies with larger sample sizes and independent experiments with placental samples should be conducted to verify these findings.


Assuntos
Blastômeros/metabolismo , Criopreservação/métodos , Transferência Embrionária/métodos , Fertilização in vitro/métodos , Sangue Fetal/metabolismo , Transcriptoma , Adulto , Análise por Conglomerados , Metilação de DNA , Feminino , Redes Reguladoras de Genes , Humanos , Recém-Nascido , Fator de Crescimento Insulin-Like II/genética , Projetos Piloto , Gravidez , Estudos Prospectivos , RNA-Seq/métodos
5.
Mol Cell Biochem ; 468(1-2): 185-193, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32200471

RESUMO

MYB Proto-Oncogene Like 2 (MYBL2) is a highly conserved member of the Myb family of transcription factors and plays a critical role in regulating cell proliferation and survival. Here we show that overexpression of MYBL2 is frequently observed in lung adenocarcinoma (LUAD) and significantly correlates with advanced stage and poor patient survival. Knockdown of MYBL2 induced apoptosis in lung cancer cells and resulted in significant inhibition of cell proliferation, migration, and invasion. Notably, we identified Non-SMC Condensin I Complex Subunit H (NCAPH) gene as a direct target of MYBL2. NCAPH expression is highly correlated with that of MYBL2 in LUAD cases and is tightly affected by MYBL2 knockdown or overexpression in vitro. Chromatin immunoprecipitation (ChIP) assays also showed that MYBL2 directly binds to the transcription start site (TSS) of NCAPH. Moreover, we provided evidence that NCAPH functions as an oncogene in lung cancer and overexpression of NCAPH could partially rescue cell death and migration blockage induced by MYBL2 knockdown. Together, these results suggest that overexpression of MYBL2 promotes proliferation and migration of lung cancer cells via upregulating NCAPH, establishing their roles as novel prognostic biomarkers as well as potential therapeutic targets for the disease.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Pulmonares/metabolismo , Proteínas Nucleares/metabolismo , Transativadores/metabolismo , Células A549 , Apoptose/genética , Biomarcadores Tumorais/genética , Carcinógenos/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Ciclo Celular/genética , Imunoprecipitação da Cromatina , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Proteínas Nucleares/genética , Ligação Proteica , Proto-Oncogene Mas , Transativadores/genética , Ativação Transcricional/genética , Regulação para Cima
6.
Am J Transl Res ; 10(9): 2940-2948, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30323880

RESUMO

Acquired resistance to chemotherapy is a major limitation for the successful treatment of lung cancer. Previously, we and others showed that formation of tumor spheres is associated with chemotherapy resistance in lung cancer cells, but the underlying mechanisms remained largely unknown. In the current study, we show that mitochondrial activity is significantly higher in A549 tumor spheres versus monolayer cells, establishing mitochondria as a putative target for antitumor therapy. To this end, we designed a peptide nucleic acids (PNAs) coupled with triphenylphosphonium (TPP) to target the displacement loop (D-loop) regulatory region of mitochondrial DNA (PNA-mito). Treatment with PNA-mito significantly disrupted mitochondrial gene expression, inhibited membrane potential and mitochondria fusion, resulting in proliferation inhibition and cell death. Consistently, in mouse xenograft models, PNA-mito could efficiently inhibit mitochondrial gene expression and block tumor growth. Treatment with a low dose of PNA-mito could significantly enhance the chemotoxicity of cisplatin (CDDP) in drug-resistant A549 tumor spheres. These results establish mitochondria-targeting PNAs as a novel strategy to enhance the accumulative therapeutic outcome of lung cancer.

7.
Oncol Lett ; 16(3): 3949-3954, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30128013

RESUMO

Yes-associated protein (YAP) serves a critical role in the initiation and progression of a variety of types of cancer via modulating the expression of genes involved in cell proliferation and the downregulation of apoptosis. Recent studies have suggested that YAP is responsible for the development of drug resistance and cancer metastasis and recurrence. However, the association between YAP and chemoresistance in lung cancer, particularly in lung cancer stem cells (LCSCs) remains largely unknown. In the current study, lung cancer cell spheres were established using the A549 cell line, which demonstrated stem cell properties. It was revealed that YAP was overexpressed in lung cancer spheres compared with normal A549 adherent cells and was associated with enhanced cisplatin (CDDP) resistance. Knockdown of YAP effectively sensitized the adherent A549 and tumor spheres to CDDP treatment and resulted in enhanced cell death. These results suggest that YAP serves a critical role in LCSCs drug resistance and YAP targeting could become a promising adjuvant to current the chemotherapy for lung cancer.

8.
Explore (NY) ; 13(5): 306-312, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28915981

RESUMO

OBJECTIVES: To explore whether transcutaneous electrical acupoint stimulation (TEAS) can improve the outcomes of in vitro fertilization (IVF). DESIGN: A prospective, randomized, and controlled study. SETTING: IVF center in a university hospital. PARTICIPANTS: Four hundred and eighty-one infertile patients with bilateral tubal blockage who were referred for IVF. Patients were randomized into four groups. INTERVENTION: TEAS was administered for 30min, respectively, at 24h before TVOR and two hours before ET. The acupoints included SP10 (Xuehai, bilateral), SP8 (Diji, bilateral), LR3 (Taichong, bilateral), ST36 (Zusanli, bilateral), EX-CA1 (Zigong, bilateral), RN4 (Guanyuan), PC6 (Neiguan, bilateral), and RN12 (Zhongwan). Based on different frequencies of TEAS, patients were grouped into a TEAS-2Hz group, a TEAS-100Hz group and a TEAS-2/100Hz group. Patients in the control group only received routine IVF treatment and no TEAS was applied on them. PRIMARY AND SECONDARY OUTCOME MEASURES: The number of mature oocytes, normally fertilized oocytes and good-quality embryos were used to evaluate oocyte developmental competence of the patients. Data of clinical pregnancy rate (CPR), implantation rate (IR), and live birth rate (LBR) were also obtained. The levels of neuropeptide Y (NPY), transforming growth factor alpha and granulocyte colony-stimulating factor in the follicular fluids were measured with enzyme-linked immunosorbent assay (ELISA). RESULTS: No significant differences were found between the control, TEAS-2Hz, TEAS-100Hz and TEAS-2/100Hz groups on the numbers of metaphase II oocytes, normally fertilized zygotes, early cleavage embryos or good quality embryos (P > .05). However, the CPR, IR and LBR of the TEAS-2/100Hz group were significantly higher than those of the other groups, respectively (P < .05). The NPY levels in the follicular fluids of TEAS-2/100Hz group were significantly higher than those of the other groups (P < .05). CONCLUSION: TEAS using a frequency of 2/100Hz could help to improve the IVF outcomes partly by increasing NPY levels in the follicular fluids.


Assuntos
Eletroacupuntura/métodos , Fertilização in vitro , Infertilidade Feminina/terapia , Estimulação Elétrica Nervosa Transcutânea , Adulto , China , Feminino , Líquido Folicular/química , Fator Estimulador de Colônias de Granulócitos/análise , Humanos , Neuropeptídeo Y/análise , Oócitos/fisiologia , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Fator de Crescimento Transformador alfa/análise , Resultado do Tratamento
9.
Tumour Biol ; 37(4): 4929-37, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26526583

RESUMO

The presence of cancer stem cells (CSCs) is the source of occurrence, aggravation, and recurrence of lung cancer. Accordingly, targeting killing the lung CSCs has been suggested to be an effective approach for lung cancer treatment. In this study, we showed that rapamycin inhibited the mammalian target of rapamycin (mTOR) signal transduction in A549 cells and improved the sensitivity to cisplatin (DDP). The mechanisms involve inhibition of the SOX2 expression, cell proliferation, epithelial-mesenchymal transition (EMT) phenotype, and sphere formation. Interestingly, knocked down SOX2 was a similar effect with rapamycin in A549 sphere. Furthermore, we showed that ectopic expression of Sox2 in A549 cells was sufficient to render them more resistant to rapamycin treatment in vitro. These data suggested that rapamycin inhibited the function of lung CSCs via SOX2. It will be of great interest to further explore the therapeutic strategies of lung cancer.


Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Fatores de Transcrição SOXB1/genética , Sirolimo/administração & dosagem , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Fatores de Transcrição SOXB1/biossíntese
10.
Int J Clin Exp Med ; 8(7): 10845-54, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26379878

RESUMO

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for degrading essentially all components of the extracellular matrix (ECM). Accumulating evidence suggests that MMPs might play a critical role in growth, invasion, and metastasis of malignant tumors. A single nucleotide polymorphism (SNP) in the promoter region of MMP-12, MMP-12 82 A/G (rs2276109), has been recognized to play a critical role in regulating the expression of MMP-12, however, its correlation with tumor susceptibility remains controversial. To address this issue, we performed meta-analysis to investigate the association MMP-12 82 A/G polymorphism and susceptibility of nine malignant tumors from 11 studies, including 6153 cancer patients and 6838 controls. Two reviewers independently screened studies for eligibility and extracted data for included studies. While overall no evident association between MMP-12 82 A/G and tumor susceptibility was observed, subgroup analysis revealed a specific role of G allele in increasing the susceptibility for epithelial ovarian carcinoma (EOC) using the allele model (fixed effects OR = 2.45, 95% CI = 1.46-4.10, P = 0.001) and the dominant model (fixed effects OR = 2.52, 95% CI = 1.49-4.24, P = 0.001). We thus suggest that G allele of MMP-12 82 A/G polymorphism is a genetic risk factor for EOC.

11.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 44(3): 237-46, 2015 05.
Artigo em Chinês | MEDLINE | ID: mdl-26350002

RESUMO

OBJECTIVE: To investigate the factors related to clinical pregnancy outcomes of in vitro fertilization-embryo transfer (IVF-ET) in women with secondary infertility. METHODS: The clinical, laboratory and follow-up data of 1129 cycles in 1099 patients with secondary infertility undergoing IVF-ET in Women's Hospital, Zhejiang University School of Medicine between July 2012 to July 2014 were retrospectively reviewed. The factors related to pregnancy outcomes were analyzed by univariate and logistic regression methods. The clinical pregnancy rates in women with different age and different number of embryos transferred were compared. The clinical outcomes of stimulation with gonadotropin releasing hormone (GnRH) agonist long protocol, GnRH agonist short protocol and GnH antagonist protocol were evaluated in secondary infertile patients aged ≥ 40 years. RESULTS: Among 1129 cycles, 376 cases (33.30%) had clinical pregnancy and 753 cases (66.70%) had no clinical pregnancy. There were significant differences in age, body mass index, basal follicle-stimulating hormone level, antral follicle number,paternal age and number of embryos transferred between pregnancy and no pregnancy groups (P<0.05); while only maternal age (OR=0.900, 95% CI: 0.873~0.928, P<0.001) and the number of embryos transferred (OR=2.248, 95% CI: 1.906~2.652, P<0.001) were the independent factors affecting the clinical pregnancy outcome of IVF-ET. There was no significant difference in clinical pregnancy rate between women aged 30~40 years with two embryos transferred and those aged<30 years with two or three embryos transferred(P>0.05). There were no significances in clinical pregnancy rate among women aged ≥ 40 years using GnRH agonist long protocol,GnRH agonist short protocol and GnRH antagonist protocol for stimulation (P>0.05). CONCLUSION: Maternal age and number of embryos transferred have independent effect on IVF-ET clinical pregnancy outcome of secondary infertile women. We suggest that no more than two embryos should be transferred for women in their thirties to minimize the risk of multiple pregnancy while still having an acceptable pregnancy rate. The pregnancy rate of patients over 40 years decreases significantly, and there is no difference in pregnancy rate by using GnRH agonist long protocol, GnRH agonist short protocol or GnRH antagonist protocol.


Assuntos
Transferência Embrionária , Fertilização in vitro , Resultado da Gravidez , Adulto , Feminino , Hormônio Foliculoestimulante , Hormônio Liberador de Gonadotropina/agonistas , Gonadotropinas , Antagonistas de Hormônios/uso terapêutico , Humanos , Infertilidade Feminina , Idade Materna , Folículo Ovariano , Indução da Ovulação , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
12.
Int J Clin Exp Pathol ; 8(6): 6287-300, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26261505

RESUMO

There is growing evidence suggesting that cancer stem cells (CSCs) are playing critical roles in tumor progression, metastasis and drug resistance. However, the role of CSCs in non-small cell lung cancer (NSCLC) remains elusive. In this study, we enriched for stem-like cells from tumor spheres derived from NSCLC cell line A549 cultured in serum-free medium. Our results showed that sphere-derived cells expressed various stem cell markers such as CD44, CD133, Sox2 and Oct4. Compared with the corresponding cells in monolayer cultures, sphere-derived cells showed marked morphologic changes and increased expression of the stem cell markers CD133. Furthermore, we found that sphere-derived cells exhibited increased proliferation, cell-cycle progression as well as drug-resistant properties as compared to A549 adherent cells. Consistently, expression of several drug resistance proteins, including lung resistance-related protein (LRP), glutathion-S-transferase-π (GST-π) and multidrug resistance proteins-1 (MRP1) were all significantly enhanced in sphere-derived cells. These results indicate the enrichment of CSCs in sphere cultures and support their role in regulating drug resistance in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/patologia , Esferoides Celulares/patologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Biomarcadores Tumorais/análise , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Citometria de Fluxo , Imunofluorescência , Humanos
13.
Int J Clin Exp Pathol ; 8(3): 2574-81, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26045763

RESUMO

Neurensin-2 (NRSN2), a small neural membrane protein which localized in small vesicles in neural cells. Recent report suggested that Neurensin-2 might play a suppressive role in tumor. While the biological functions and molecular mechanisms in cancer progression remain unknown. We retrieved Oncomine Database and found that NRSN2 is commonly highly expressed in non-small cell lung cancer (NSCLC). We examined the levels of NRSN2 in 18 pairs of NSCLC and adjacent tissues and found that NRSN2 was overexpressed in malignant tissues. Both loss and gain of function experiments in NSCLC cell lines suggest that NRSN2 promotes cell growth, but no effects in cell invasion. Further investigation show that NRSN2 could affect phosphatidylinositol 3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling. Taken together, our findings suggest that NRSN2 promotes non-small cell lung cancer cell growth through PI3K/Akt/mTOR pathway.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Proteínas de Membrana/biossíntese , Transdução de Sinais/fisiologia , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno , Reação em Cadeia da Polimerase em Tempo Real , Serina-Treonina Quinases TOR/metabolismo , Transfecção
14.
BMC Med ; 12: 240, 2014 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-25511686

RESUMO

BACKGROUND: The increasing number of babies conceived by in vitro fertilization and embryo transfer (IVF-ET) shifts concern from pregnancy outcomes to long-time health of offspring. Maternal high estradiol (E2) is a major characteristic of IVF-ET and lasts throughout the first trimester of pregnancy. The fetal thyroid develops during this period and may thus be affected by exposure to the supra-physiological E2. The aim of this study is to investigate whether the high E2 maternal environment in the first trimester increases the risk of thyroid dysfunction in children born following IVF-ET. METHODS: A cross-sectional survey design was used to carry out face-to-face interviews with consecutive children attending the hospital. A total of 949 singletons born after fresh embryo transfer (ET) (n=357), frozen ET (n=212), and natural conception (NC) (n=380), aged 3 to 10 years old, were included. All children were thoroughly examined. Meanwhile, another 183 newborns, including 55 fresh ET, 48 frozen ET, and 80 NC were studied. Levels of serum T3, FT3, T4, FT4, and TSH and levels of maternal E2 at different stages of the first trimester were examined. RESULTS: The mean serum E2 levels of women undergoing fresh ET during the first trimester of pregnancy were significantly higher than those of the women undergoing frozen ET or following NC. The thyroid hormone profile, especially the levels of T4, FT4, and TSH, were significantly increased in 3- to 10-year-old children conceived by fresh ET compared to NC. The same tendency was confirmed in newborns. However, levels of T4 and TSH in the frozen ET group were nearer to that of the NC group. Furthermore, levels of T4 and FT4 in fresh ET were positively correlated with maternal serum levels of E2 during early pregnancy. CONCLUSIONS: The maternal high E2 environment in the first trimester is correlated with increased risk of thyroid dysfunction. Frozen ET could reduce risks of thyroid damage in children conceived by IVF. Further studies are needed to confirm these findings and to better determine the underlying molecular mechanisms and clinical significance. TRIAL REGISTRATION: ChicCTR-OCC-14004682 (22-05-2014).


Assuntos
Transferência Embrionária , Estradiol/efeitos adversos , Fertilização in vitro , Doenças do Recém-Nascido/sangue , Exposição Materna/efeitos adversos , Hormônios Tireóideos/sangue , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/etiologia , Masculino , Gravidez , Resultado da Gravidez , Primeiro Trimestre da Gravidez
15.
J Clin Endocrinol Metab ; 99(12): E2494-503, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25268391

RESUMO

CONTEXT: The cardiovascular dysfunction in children born with assisted reproductive technologies has been of great concern. However, the association of ovarian hyperstimulation syndrome (OHSS), a complication of assisted reproductive technologies, with worse cardiovascular functions and underlying mechanism remains unknown. OBJECTIVES: The objective of the study was to assess the cardiovascular functions of children born to mothers with OHSS and investigate the underlying regulator(s). DESIGN AND SETTING: This was a retrospective cohort recruited in a university hospital. PARTICIPANTS AND METHODS: We assessed the cardiovascular functions by Doppler echography in 42 children born to OHSS women, 34 children of mothers with non-OHSS in vitro fertilization, and 48 spontaneously conceived (SC) children (mean age ∼ 4.5 y). Groups were matched for gestational age at delivery and birth weight. An isobaric tag for relative and absolute quantitation-labeled proteomics analysis was performed with another set of umbilical arteries from OHSS and SC pregnancies (n = 3 for both groups). RESULTS: Children of OHSS mothers showed a significantly decreased mitral ratio of early to late mitral peak velocities, reduced systolic and diastolic diameters of common carotid arteries, and impaired flow-mediated dilation compared with non-OHSS in vitro fertilization and SC children. Intima-media thickness and arterial stiffness indices were similar in the three groups. In the proteomics study, 1640 proteins were identified from OHSS and SC umbilical arteries, and 40 differentially expressed proteins were selected for further analysis. Estradiol and progesterone were identified as activated upstream regulators. CONCLUSIONS: Children born to ovarian-hyperstimulated women displayed cardiovascular dysfunctions. The underlying mechanisms may involve the effects of supraphysiological estradiol and progesterone levels.


Assuntos
Doenças Cardiovasculares/etiologia , Estradiol/sangue , Síndrome de Hiperestimulação Ovariana/complicações , Progesterona/sangue , Proteômica , Doenças Cardiovasculares/genética , Criança , Pré-Escolar , Estudos de Coortes , Ecocardiografia , Feminino , Testes de Função Cardíaca , Humanos , Masculino , Síndrome de Hiperestimulação Ovariana/genética , Estudos Retrospectivos , Artérias Umbilicais/química
16.
Sci Rep ; 4: 5028, 2014 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-24848522

RESUMO

The study was to explore whether auricular acupressure (AA) can relieve anxiety during the period from trans-vaginal oocyte retrieval to the embryo transfer in IVF treatment and whether AA can improve the outcomes of IVF. 305 infertile patients with tubal blockage who were referred for IVF were included. The women were randomized into a control group with 102 cases, a Sham-AA group with 102 cases and an AA group with 101 cases. The anxiety levels were rated with Spielberger's State Trait Anxiety Inventory and the Amsterdam Preoperative Anxiety and Information Scale. Data of clinical pregnancy rate (CPR), implantation rate (IR) and live birth rate (LBR) were obtained. The levels of neuropeptide Y (NPY) and transforming growth factor alpha (TGF-alpha) in the follicular fluids were detected with ELISA. After treatment, in AA group, the levels of state anxiety, preoperative anxiety and need-for-information were significantly lower, whereas CPR, IR, LBR and NPY levels in the follicular fluids were markedly higher than Sham-AA group and control group. We concluded that AA could help to reduce anxiety levels associated with IVF and improves the outcomes of IVF partly through increasing the levels of NPY in the follicular fluids.


Assuntos
Terapia por Acupuntura , Ansiedade/terapia , Fertilização in vitro , Pontos de Acupuntura , Adulto , Ansiedade/etiologia , Coeficiente de Natalidade , Estudos de Casos e Controles , Transferência Embrionária , Feminino , Seguimentos , Humanos , Técnicas In Vitro , Gravidez , Taxa de Gravidez , Prognóstico , Estudos Prospectivos
17.
Intern Med ; 50(12): 1323-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21673470

RESUMO

Pulmonary veno-occlusive disease (PVOD) is a rare and usually survival poor disorder. We report a patient with a long history of progressive dyspnea of over 8 years, who with a diagnosis of chronic cor pulmonale confirmed elsewhere, was ultimately diagnosed as PVOD via histological analysis of a lung biopsy. After treatment with combined bosentan, diuretics and digoxin, his symptoms and function improved. This case highlights that PVOD is an under-recognised and often misdiagnosed disease, especially in its chronic form. Understanding its pathogenesis, its poor response to medical therapy and its dismal prognosis remain challenges for the treatment of PVOD.


Assuntos
Pneumopatia Veno-Oclusiva/diagnóstico , Adulto , Anti-Hipertensivos/administração & dosagem , Biópsia , Bosentana , Cardiotônicos/administração & dosagem , Diagnóstico Diferencial , Digoxina/administração & dosagem , Diuréticos/administração & dosagem , Quimioterapia Combinada , Dispneia/etiologia , Humanos , Hipertensão Pulmonar/diagnóstico , Masculino , Doença Cardiopulmonar/diagnóstico , Pneumopatia Veno-Oclusiva/tratamento farmacológico , Pneumopatia Veno-Oclusiva/fisiopatologia , Sulfonamidas/administração & dosagem , Fatores de Tempo , Tomografia Computadorizada por Raios X
18.
Int J Cancer ; 129(4): 820-31, 2011 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-21520032

RESUMO

Energy metabolism is the foundation of survival for all organisms, and mitochondria are the most important energy-supplying organelles in eukaryotic cells. However, the mitochondrial and energy/metabolism-related properties of cancer stem cells (CSCs), the stem cell-like subpopulation in tumor masses, remain unknown. In our study, we compared the masses of mitochondria and mitochondrial DNA (mtDNA), the mitochondrial membrane potential (Δψm), oxygen/glucose consumption, and the concentration of reactive oxygen species (ROS) and ATP between lung CSCs (LCSCs) and non-LCSCs. In addition, the change in features during differentiation was examined. Some mitochondrial and energy metabolism-related properties, such as perinuclear mitochondrial distribution, a lower quantity of mtDNA, higher Δψm, lower oxygen/glucose consumption, and lower intracellular concentrations of ROS and ATP, can be used as indicators of LCSCs.


Assuntos
Metabolismo Energético , Neoplasias Pulmonares/diagnóstico , Potencial da Membrana Mitocondrial , Mitocôndrias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Trifosfato de Adenosina/metabolismo , Apoptose , Diferenciação Celular , DNA Mitocondrial/genética , Glucose/metabolismo , Humanos , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/metabolismo , Oxigênio/metabolismo , Células Tumorais Cultivadas
19.
Stem Cell Rev Rep ; 7(1): 153-60, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20306158

RESUMO

It is believed that cancer stem cells (CSCs) are precursors for the formation, development, and recurrence of malignant tumors. However, it has proven difficult to isolate and enrich these rare, undifferentiated cells from heterogeneous tumor masses. With some existing reports and preliminary results in mind, we hypothesized that the mitochondrial membrane potential within a tumor mass was heterogeneous and could be used as a tool to isolate and enrich CSCs.


Assuntos
Separação Celular/métodos , Potencial da Membrana Mitocondrial , Neoplasias/patologia , Células-Tronco Neoplásicas/patologia , Antígeno AC133 , Antígenos CD/metabolismo , Linhagem Celular Tumoral , Glicoproteínas/metabolismo , Humanos , Modelos Biológicos , Peptídeos/metabolismo , Células da Side Population/patologia , Esferoides Celulares/patologia
20.
Di Yi Jun Yi Da Xue Xue Bao ; 25(10): 1314-5, 2005 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-16234120

RESUMO

OBJECTIVE: To investigate the role of substance P (SP) in chronic obstructive pulmonary disease (COPD) or asthma. METHOD: Plasma and sputum samples were obtained from 26 COPD patients and 20 asthmatic patients as well as 12 healthy subjects for measurement of SP content. RESULTS: Patients with COPD had significantly higher levels of SP in the plasma (7.9+/-2.6 pmol/L) and sputum (53.8+/-12.5 pmol/L) than the healthy subjects (3.6+/-1.7 pmol/L and 6.2+/-2.3 pmol/L, respectively, P<0.01). The asthmatic patients also had significantly higher SP levels (8.3+/-3.1 pmol/L and 46.9+/-10.2 pmol/L, respectively) than the healthy subjects, but there was no significant difference between COPD and asthmatic patients (P>0.05). CONCLUSION: SP may be involved in the airway inflammation process in COPD and asthma.


Assuntos
Asma/sangue , Pneumopatias Obstrutivas/sangue , Escarro/química , Substância P/análise , Idoso , Asma/metabolismo , Feminino , Humanos , Pneumopatias Obstrutivas/metabolismo , Masculino , Pessoa de Meia-Idade
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