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OBJECTIVES: Infertile patients are vulnerable to mental disorders. However, a time-dependent model predicting the onset of mental disorders specific to infertile patients is lacking. This study examined the risk factors for the development of mental disorders in infertile patients and measured the duration until the occurrence of mental disorders after a diagnosis of infertility. METHODS: A total of 13,317 infertile patients in the 2002-2013 Taiwan National Health Insurance Research Database were observed. The 11 independent variables included in the hypothesised model, together with the dates of infertility and mental disorder diagnoses, were analysed using Cox proportional hazards. Data-mining methods using C5.0 and Apriori supplemented the statistical analyses. RESULTS: The total prevalence rate of mental disorders among infertile patients in Taiwan was 12.41%, including anxiety (4.66%), depression (1.81%) and other mental disorders (5.94%). The average time interval for onset of mental illness identified using survival analysis was 1.67 years. Income, occupation, treatment method, co-morbidity, region and hospital level and ownership were significant predictors of development of mental illness (all p < .05). CONCLUSIONS: The four categories of factors associated with time-dependent onset were demographics, health, health care provider and geographical characteristics. Certain patient characteristics may predict a higher likelihood of onset of a specific mental disorder. Clinical practitioners may use the findings to identify high-risk patients and make timely health interventions.
Assuntos
Infertilidade Feminina/psicologia , Infertilidade Masculina/psicologia , Transtornos Mentais/epidemiologia , Adulto , Fatores Etários , Ansiedade/epidemiologia , Estudos de Coortes , Comorbidade , Mineração de Dados , Depressão/epidemiologia , Feminino , Nível de Saúde , Humanos , Revisão da Utilização de Seguros , Masculino , Pessoa de Meia-Idade , Prevalência , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Fatores Socioeconômicos , Análise de Sobrevida , Taiwan/epidemiologia , Fatores de TempoRESUMO
In this paper, we propose a microfluidic device capable of generating a retarding flow field for the sorting and separation of human motile sperm in a high-throughput manner. The proposed sorting/separation process begins with a rapid flow field in a straight-flow zone to carry sperm into a sorting zone to maintain the sperm's mobility. The sorting zone consists of a diffuser-type sperm sorter to differentiate sperm with different motilities based on the flowing upstream nature of human sperm in a retarding flow field. The dead sperm will then be separated from the live ones by passing through a dumbbell flow field to the outlet for disposal. The proposed flowing upstream sperm sorter (FUSS) is designed to imitate the selection mechanism found in the female body when sperm swim into the uterus. The experimental results demonstrate the utility of this device with regard to throughput (approximately 200 000 sperm per minute and a maximum of 200 million cells per mL), efficiency (90% of selected sperm are mobile), and the ability to select sperm with high motility (â¼20% of sperm with a velocity exceeding 120 µm s-1). The proposed device is suitable for intrauterine insemination as well as in vitro fertilization thanks to the highly efficient sorting process not interfering with the natural function and energy resource of human sperm.
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Separação Celular , Dispositivos Lab-On-A-Chip , Análise do Sêmen , Espermatozoides/citologia , Humanos , Masculino , Motilidade dos EspermatozoidesRESUMO
Chemotherapy is the main approach for treating advanced and recurrent carcinoma, but the clinical performance of chemotherapy is limited by relatively low response rates, drug resistance, and adverse effects that severely affect the quality of life of patients. An association between epithelial-mesenchymal transition (EMT) and chemotherapy resistance has been investigated in recent studies. Our recent studies have found that the aqueous extract of Solanum nigrum (AESN) is a crucial ingredient in some traditional Chinese medicine formulas for treating various types of cancer patients and exhibits antitumor effects. We evaluated the suppression of EMT in MCF-7 breast cancer cells treated with AESN. The mitochondrial morphology was investigated using Mitotracker Deep-Red FM stain. Our results indicated that AESN markedly inhibited cell viability of MCF-7 breast cancer cells through apoptosis induction and cell cycle arrest mediated by activation of caspase-3 and production of reactive oxygen species. Furthermore, mitochondrial fission was observed in MCF-7 breast cancer cells treated with AESN. In addition to elevation of E-cadherin, downregulations of ZEB1, N-cadherin, and vimentin were found in AESN-treated MCF-7 breast cancer cells. These results suggested that AESN could inhibit EMT of MCF-7 breast cancer cells mediated by attenuation of mitochondrial function. AESN could be potentially beneficial in treating breast cancer cells, and may be of interest for future studies in developing integrative cancer therapy against proliferation, metastasis, and migration of breast cancer cells.
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Neoplasias da Mama/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Extratos Vegetais/farmacologia , Solanum nigrum/química , Neoplasias da Mama/tratamento farmacológico , Caderinas/metabolismo , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7RESUMO
Chemotherapy, a major approach was used in carcinoma treatment, always involves the development of drug resistance as well as side-effects that affect the quality of patients' lives. An association between epithelial-mesenchymal transition (EMT) and chemotherapy resistance was established recently. We demonstrate in this paper that the aqueous extract of Paris polyphylla (AEPP)-a traditional Chinese medicine-can be used in various cancer types for suppression of carcinogenesis. We evaluated the suppressions of EMT and mitochondrial activity by AEPP treatment in a high-glucose (HG) induced-human ovarian carcinoma cell line (OVCAR-3 cells). The mitochondrial morphology was investigated using MitoTracker Deep Red FM staining. Our results indicated that AEPP reduced the viability of OVCAR-3 cells considerably through induction of apoptosis. However, this inhibitory potential of AEPP was attenuated by HG induction in OVCAR-3 cells. The levels of estrogen-related receptor (ERR)-alpha activator and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha were elevated by HG induction, but were suppressed by AEPP treatment. Down-regulations of cell survival and EMT were oberved in OVCAR-3 cells through suppression of PGC-1alpha by AEPP treatment. These results were confirmed through PGC-1alpha knockdown and overexpression in OVCAR-3 cells. Thus, AEPP can be beneficial for treating ovarian cancer and has potential for development of an integrative cancer therapy against ovarian cancer proliferation, metastasis, and migration.
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Melanthiaceae/química , Neoplasias Ovarianas/tratamento farmacológico , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/biossíntese , Extratos Vegetais/administração & dosagem , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Medicina Tradicional Chinesa , Neoplasias Ovarianas/patologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Extratos Vegetais/químicaRESUMO
BACKGROUND: Advanced glycation end products (AGEs) signal through the receptor for AGE (RAGE), which can lead to hepatic fibrosis in hyperglycemia and hyperlipidemia. We investigated the inhibitory effect of aqueous extracts from Solanum nigrum (AESN) on AGEs-induced RAGE signaling and activation of hepatic stellate cells (HSCs) and hyperglycemia induced by high-fat diet with ethanol. METHODS: An animal model was used to evaluate the anti-hepatic fibrosis activity of AESN in rats fed a high-fat diet (HFD; 30%) with ethanol (10%). Male Wistar rats (4 weeks of age) were randomly divided into four groups (n = 6): (1) control (basal diet); (2) HFD (30%) + ethanol (10%) (HFD/ethanol); (3) HFD/ethanol + AESN (100 mg/kg, oral administration); and (4) HFD/ethanol + pioglitazone (10 mg/kg, oral administration) and treated with HFD for 6 months in the presence or absence of 10% ethanol in dietary water. RESULTS: We found that AESN improved insulin resistance and hyperinsulinemia, and downregulated lipogenesis via regulation of the peroxisome proliferator-activated receptor α (PPARα), PPARγ co-activator (PGC-1α), carbohydrate response element-binding protein (ChREBP), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) mRNA levels in the liver of HFD/ethanol-treated rats. In turn, AESN may delay and inhibit the progression of hepatic fibrosis, including α-smooth muscle actin (α-SMA) inhibition and MMP-2 production. CONCLUSIONS: These results suggest that AESN may be further explored as a novel anti-fibrotic strategy for the prevention of liver disease.
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Dieta Hiperlipídica/efeitos adversos , Etanol/efeitos adversos , Hiperglicemia/tratamento farmacológico , Cirrose Hepática/prevenção & controle , Extratos Vegetais/administração & dosagem , Solanum nigrum/química , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Produtos Finais de Glicação Avançada/metabolismo , Células Estreladas do Fígado/efeitos dos fármacos , Hiperglicemia/induzido quimicamente , Lipogênese/efeitos dos fármacos , Cirrose Hepática/genética , Masculino , Pioglitazona , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Tiazolidinedionas/administração & dosagem , Tiazolidinedionas/uso terapêuticoRESUMO
Chemotherapy damages the reproductive system by enhancing apoptosis, and evidence suggests that targeted anti-apoptotic therapy may preserve fertility in patients receiving chemotherapy. To investigate the protective effect of sphingosine-1-phosphate (S1P) on chemotherapeutic agent-induced ovarian gonadotoxicity, busulfan-treated female mice were pre-treated with low (0.5 mM) and high (2.0 mM) doses of S1P or vehicle 1 h before busulfan injection. In the S1P groups, each mouse was injected with low-dose S1P in one ovary and high-dose S1P in the contralateral ovary. Four weeks later, the ovaries were removed for histological and biochemical examinations. Caspase 3 immunoreactivity was greater in mice treated with busulfan compared with mice pre-treated with S1P, in which more primordial follicles were observed (P < 0.05). The mRNA level of anti-Müllerian hormone was higher in mice pre-treated with S1P than those that received busulfan only, indicating a better ovarian function in mice pre-treated with S1P. No difference was observed in the levels of growth differentiation factor-9 among all groups. In conclusion, S1P protects primordial follicles from chemotherapy-induced gonadotoxicity, and may partially preserve ovarian function.
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Antineoplásicos/efeitos adversos , Apoptose/efeitos dos fármacos , Lisofosfolipídeos/metabolismo , Ovário/efeitos dos fármacos , Esfingosina/análogos & derivados , Animais , Hormônio Antimülleriano/metabolismo , Antineoplásicos/química , Bussulfano/efeitos adversos , Bussulfano/química , Caspase 3/metabolismo , Dano ao DNA/efeitos dos fármacos , Feminino , Fertilidade/efeitos dos fármacos , Células da Granulosa/efeitos dos fármacos , Imuno-Histoquímica , Camundongos , Folículo Ovariano/efeitos dos fármacos , RNA Mensageiro/metabolismo , Esfingosina/metabolismoRESUMO
BACKGROUND: Pulmonary hypoplasia is associated with reduced lung function in infancy. The aim of this study was to evaluate the hypothesis that children exposed to oligohydramnios display an increased risk of hospitalization for respiratory illness by using a population-based matched-cohort design. METHODS: We used three nationwide population-based data sets to identify 5,228 women who gave birth during 2004 to 2007 and were diagnosed with oligohydramnios during the third trimester of pregnancy. A cohort of 20,912 unaffected pregnant women was matched with these cases, according to neonatal sex and gestational age, maternal age and education, and level of prenatal care. Respiratory hospitalization and respiratory failure were defined using discharge diagnostic codes. RESULTS: Oligohydramnios-exposed children had an 8% higher incidence rate of respiratory hospitalization and an 80% higher incidence rate of respiratory failure, compared with children without oligohydramnios exposure. This risk remained after adjusting for all potential risk factors. Cox regression analyses indicated that the adjusted hazard ratios of respiratory hospitalization and respiratory failure were 1.07 (95% confidence interval (CI): 1.01-1.15; P = 0.030) and 2.20 (95% CI: 1.26-3.84; P = 0.005), respectively. CONCLUSION: Children exposed to oligohydramnios during the third trimester of pregnancy display an increased risk of hospitalization for respiratory illness.
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Hospitalização , Oligo-Hidrâmnio/fisiopatologia , Vigilância da População , Infecções Respiratórias/etiologia , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Gravidez , Infecções Respiratórias/fisiopatologia , Fatores de RiscoRESUMO
An adequate thickness and pattern of the pre-ovulatory endometrium is considered one of the essential requirements for a successful pregnancy. Although various methods for increasing endometrial thickness have been proposed, the real value of these interventions remains controversial. Here, we present a case of successful administration of extended estrogen supplementation before conventional controlled ovarian hyperstimulation in a woman who had experienced repeated implantation failure because of an unresponsive thin endometrium. After the estrogen supplement was administrated for an extended period, the in vitro fertilization/embryo transfer in this patient led to an uneventful twin pregnancy and delivery at term.
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Endométrio/efeitos dos fármacos , Estradiol/análogos & derivados , Estrogênios/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , Adulto , Transferência Embrionária , Endométrio/patologia , Endométrio/fisiopatologia , Estradiol/uso terapêutico , Feminino , Fertilização in vitro , Humanos , Infertilidade Feminina/patologia , Infertilidade Feminina/fisiopatologia , Infertilidade Feminina/terapia , Gravidez , Gravidez de Gêmeos , Superovulação , Nascimento a TermoRESUMO
OBJECTIVE: To study whether the methylation status of cervical secretions can reflect the ability of the endometrium to allow embryo implantation. DESIGN: Case-control study. SETTING: In vitro fertilization centers. PATIENT(S): Women undergoing embryo transfer cycles, in which at least 1 good-quality embryo was transferred. INTERVENTION(S): Collection of cervical secretions during the procedure of embryo transfer. MAIN OUTCOME MEASURE(S): Methylation profiles of cervical secretions in relation to pregnancy outcomes. RESULT(S): Genome-wide methylation profiles differ between cervical secretions from pregnancy and nonpregnancy cycles. Clustering analysis on the basis of the top 2,000 differentially methylated probes of cervical secretions from 28 pregnancy and 29 nonpregnancy cycles correctly categorized 86.0% of the samples in terms of conceptional status, which was verified in selected genes by quantitative methylation-specific polymerase chain reaction and validated in another independent sample set. The combination of selected genes was estimated to predict pregnancy outcomes with a maximal area under the receiver operating characteristic curve of 0.83. CONCLUSION(S): The methylation profiles of cervical secretions were associated with pregnancy outcomes in embryo transfer cycles. Although not clinically useful at present, deoxyribonucleic acid methylation in cervical secretions may shed new light on the less invasive assessment of endometrial receptivity.
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Transferência Embrionária , Resultado da Gravidez , Estudos de Casos e Controles , DNA , Transferência Embrionária/métodos , Feminino , Humanos , Metilação , GravidezRESUMO
Tamoxifen has been reported to be oestrogenic on the lower genital tract. To evaluate its potential positive effect on the endometrium, and consequently early miscarriage and ongoing pregnancy rate, a prospective study was employed in patients for intrauterine insemination who failed to develop an adequate endometrial thickness in a previous ovulatory cycle. Ovarian stimulation was initiated with tamoxifen 40 mg/day from day 3 of the menstrual cycle for 7 days or clomiphene 100 mg/day for 5 days, in combination with 150 IU of human menopausal gonadotrophin on alternate days starting on day 4. Human chorionic gonadotrophin (HCG) was administered when at least one leading follicle was larger than 20 mm. Intrauterine insemination was accomplished 24-36 h after HCG injection and luteal phase supplement was achieved with micronized progesterone 200 mg transvaginally per day. It was found that tamoxifen-treated patients required more stimulation days and used more gonadotrophin, but recruited less follicles larger than 14 mm than clomiphene-treated patients. However, a significantly increased endometrial thickness (P < 0.001) and pregnancy rate (P = 0.015), decreased early miscarriage rate (P = 0.001) and thus improved ongoing pregnancy (P < 0.001) rate were noted in tamoxifen-treated patients. These results suggest that although tamoxifen may not be a first-line treatment in patients with adequate endometrium, it may be a promising alternative for patients with thin endometrium.
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Endométrio/anormalidades , Gonadotropinas/uso terapêutico , Infertilidade Feminina/terapia , Indução da Ovulação/métodos , Tamoxifeno/farmacologia , Adulto , Clomifeno/uso terapêutico , Endométrio/patologia , Antagonistas de Estrogênios/uso terapêutico , Feminino , Fármacos para a Fertilidade Feminina/uso terapêutico , Humanos , Masculino , Gravidez , Taxa de Gravidez , Injeções de Esperma Intracitoplásmicas/métodosRESUMO
BACKGROUND: Certified nursing assistants (CNAs) in palliative care units often encounter the death of patients and undergo emotional burdens because of their altruistic practices. However, the influences of altruism and perceptions of death on the work morale of CNAs remain unclear. The fact that morale can be improved by modifying related factors justifies the necessity of a theoretical model of morale for CNAs. However, such a model is currently absent. Based on relevant literature, factors including altruism, social support, perceptions of death, and job satisfaction are related to morale through the mediation of job stress. AIM: This study was aimed toward determining the influencing factors and developing a structural model of morale with regard to CNAs working in palliative care units. DESIGN: The hypothesized model was tested in a cross-sectional design with structural equation modeling using AMOS 23. SETTING/PARTICIPANTS: A total of 413 CNAs from five hospice units in Taiwan participated in the survey. RESULTS: Goodness-of-fit indexes, including χ2/DF = 2.187, PGFI = 0.461, and PNFI = 0.462, among others, confirmed the modified model fit the data well. Altruism, social support, perceptions of death, and job satisfaction were negatively related to job stress (-0.238, -0.196, -0.204, and -0.131, respectively). Altruism and social support positively affected job satisfaction (0.635 and 0.553). Factors directly affecting morale included altruism, social support, job stress, and job satisfaction (0.837, 0.711, -0.244, and 0.540, respectively). The relationship between altruism and morale was the strongest among all the direct paths toward morale. Job stress was the major mediator in these relationships. CONCLUSION: Altruism is imperative for morale. The confirmed model is called the Five Constructs to Morale (5CM) model. These findings indicate the need to assess the levels of altruism and perceptions of death during the recruitment of CNAs. From the perspective of human resource management and organizational behavior, CNAs with a high level of altruism and a positive attitude toward death assure the well-being of end of life patients because of work involvement and commitment to the challenging work of hospice care. The cultivation of a supportive environment and coping strategies are suggested for the management of CNAs facing patient death. Hospice care decision makers should carefully assess morale levels among health professionals by applying the 5CM model. Identifying modifiable factors that can improve morale among nursing staff in hospice care to ensure work fulfillment and quality care merits emphasis in clinical practice. The establishment of effective strategies to facilitate the work morale of nursing staff is suggested for palliative care units. Morale improvement related task should be a global public health priority.
Assuntos
Cuidados Paliativos na Terminalidade da Vida , Modelos Estatísticos , Moral , Assistentes de Enfermagem/psicologia , Adulto , Feminino , Humanos , Satisfação no Emprego , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Cordycepin (3'-deoxyadenosine) is a compound for antitumor, which has been found to exert antiangiogenic, antimetastatic, and antiproliferative effects, as well as inducing apoptosis. However, the association between cancer metastasis and mitochondrial activity in cordycepin-treated ovarian carcinoma cells remains unclear. The 50 and 100 µM of cordycepin inhibits mitochondrial fusion and induces mitochondrial fission, respectively. These suggested that cordycepin showed the down-regulation of mitochondrial function and limitation of energy production. Because of activation of mitochondria and generation of energy are needed in cancer cell migration/invasion. After 24 h treatment, cordycepin suppresses epithelial-mesenchymal transition and migration in ovarian carcinoma cells through inhibiting estrogen-related receptor (ERR)-α. The ERRα is a co-transcription factor for gene expressions associated with mitochondrial fusion. Our results indicate that cordycepin suppresses metastasis and migration of ovarian carcinoma cells via inhibiting mitochondrial activity in non-toxic concentrations, and cordycepin has potential benefits in ovarian cancer therapy.
Assuntos
Antineoplásicos/farmacologia , Desoxiadenosinas/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Receptores de Estrogênio/antagonistas & inibidores , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Técnicas de Silenciamento de Genes , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Receptor ERRalfa Relacionado ao EstrogênioRESUMO
Chemotherapy is one of the main approach for ovarian cancer. Cancer stem cells (CSCs) escape chemotherapy and lead to chemoresistance. We previously demonstrated that cordycepin (Cd) inhibited metastasis in human ovarian carcinoma cells, the aim of this study is to investigate the effects of Cd on ovarian cancer stemness. TGF-beta was used to induce chemoresistance of chemotherapeutic agent cisplatin in SKOV-3 ovarian cancer cells. After treating with 100 µM of Cd, cell viability, the percentage of cancer stem cells, and the levels of matrix metalloproteinases (MMPs) were decreased in TGF-beta-induced SKOV-3 cells. Treatment of Cd recovered E-cadherin levels and inhibited vimentin levels while TGF-beta treatment significantly increased the expression of vimentin and PGC-1alpha, and decreased E-cadherin levels in SKOV-3 cells, indicating that the action of Cd on cancer stemness may contribute to the regulation of epithelial-mesenchymal transition (EMT). Cd efficiently attenuated chemoresistance caused by TGF-beta in SKOV-3 cancer stem cells to promote the cytotoxicity of cisplatin.
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OBJECTIVE: To evaluate the impact of the number of retrieved oocytes on pregnancy outcome. MATERIALS AND METHODS: We retrospectively examined the cycles of 2491 women undergoing in vitro fertilization therapy at Taipei Medical University (Taipei, Taiwan) from August 1995 to March 2009. We divided them into three groups based on their response rate (where H = high, M = middle, and L = low). We conducted this study to evaluate and compare pregnancy outcome in these three groups. RESULTS: The total number of retrieved oocytes had a significantly positive correlation with peak E2 levels, and the number of fertilized oocytes, good quality embryos, and available frozen embryos. The number of retrieved oocytes had a positive correlation with pregnancy rates and a negative correlation with fertilization rates. The implantation and abortion rates among the three groups were essentially the same. Compared to the middle and higher responders, the pregnancy rates for lower responders were significantly lower. The pregnancy rates for middle responders and higher responders were not significantly different. CONCLUSION: The benefits of more retrieved oocytes between the lower and the middle responders were obvious. However, the benefits and risks for retrieving more oocytes for the middle and the higher responders remained controversial.
Assuntos
Implantação do Embrião , Transferência Embrionária/métodos , Fertilização in vitro/métodos , Recuperação de Oócitos/estatística & dados numéricos , Indução da Ovulação/métodos , Adulto , Fatores Etários , Transferência Embrionária/estatística & dados numéricos , Estrogênios/sangue , Feminino , Hormônio Foliculoestimulante/administração & dosagem , Humanos , Recuperação de Oócitos/métodos , Gravidez , Resultado da Gravidez , Taxa de Gravidez , Estudos RetrospectivosRESUMO
Endometrial cancer is the most common cancer in women, typically with onset after menopause. Isoliquiritigenin (ISL), a licorice flavonoid, was previously shown to have anti-oxidant, anti-inflammatory, and tumor suppression effects. In this study, we investigated the anti-tumor effect of ISL on human endometrial cancer both in vitro and in vivo. We used telomerase-immortalized human endometrial stromal cells (T-HESCs) and human endometrial cancer cell lines (Ishikawa, HEC-1A, and RL95-2 cells) as targets. The effects of ISL on cell proliferation, cell cycle regulation, and apoptosis or autophagy-related protein expression were examined. In addition, we conducted in vivo experiments to confirm the inhibitory effects of ISL on cancer cells. ISL significantly inhibited the viability of cancer cells in a dose- and time-dependent manner but with little toxicity on normal cells. In addition, flow cytometry analysis indicated that ISL induced sub-G1 or G2/M phase arrest. ISL treatment activated the extracellular signal regulated kinase signaling pathway to enhance the protein expression of caspase-7/LC3BII associated with apoptosis/autophagy. Furthermore, ISL suppressed xenograft tumor growth in vivo. Taken together, these findings suggest that ISL may induce apoptosis, autophagy, and cell growth inhibition, indicating its potential as a therapeutic agent for human endometrial cancer.
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Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Chalconas/farmacologia , Animais , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Modelos Animais de Doenças , Neoplasias do Endométrio , Feminino , Humanos , Camundongos , Modelos Biológicos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Chemotherapy is a major clinical treatment for managing patients with advanced and recurrent ovarian cancer. However, the clinical performance of chemotherapy is limited, and adverse effects have been observed. Integrating chemotherapy with current chemotherapeutic drugs and novel antitumor ingredients might improve the clinical performance of current chemotherapy for ovarian cancer. The aqueous extract of Solanum nigrum leaves (AE-SN), a key ingredient in many traditional Chinese medicine formulae, has exhibited tumor suppression efficacy in numerous human cancer cells but not in ovarian cancer cells. In this study, tumor suppression efficacy was determined using the ES-2, SKOV-3, and OVCAR-3 human ovarian cancer cell lines. The half-maximal inhibitory concentrations of the AE-SN in ES-2 and SKOV-3 cells were 1.052 and 1.779 mg/mL, respectively. AE-SN treatment increased the accumulation of mammalian microtubule-associated protein 1 light chain 3 A/B, an autophagic cell marker, in all the tested cell lines; however, it activated the cleavage of caspase-3, an apoptotic marker, only in SKOV-3 cells. Furthermore, the AE-SN also promoted tumor suppression efficiency of cisplatin, doxorubicin, and docetaxel in the tested ovarian cancer cells. In addition, AE-SN-enhanced cell death was associated with AE-SN-induced caspase-3 cleavage in SKOV-3 cells. In conclusion, the AE-SN exhibited tumor suppression efficacy and improved the tumor suppression efficiency of cisplatin, doxorubicin, and docetaxel in human ovarian cancer cells. Therefore, the AE-SN is a candidate antitumor ingredient that can be used in developing future integrated chemotherapy for managing ovarian cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Solanum nigrum/química , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Docetaxel , Doxorrubicina/administração & dosagem , Sinergismo Farmacológico , Feminino , Humanos , Concentração Inibidora 50 , Neoplasias Ovarianas/patologia , Folhas de Planta , Taxoides/administração & dosagemRESUMO
OBJECTIVE: Patients with infertility are a high risk group in depression and anxiety. However, an existing theoretically and empirically validated model of stressors, stress, and mental symptoms specific for infertile patients is still a void. This study aimed to determine the related factors and their relational structures that affect the level of depressive and anxiety symptoms among infertile patients. METHODS: A cross-sectional sample of 400 infertility outpatients seeking reproduction treatments in three teaching hospitals across Taiwan participated in the structured questionnaire survey in 2011. The hypothesized model comprising 10 latent variables was tested by Structural Equation Modeling using AMOS 17. RESULTS: Goodness-of-fit indexes, including χ2/DF = 1.871, PGFI = 0.746, PNFI = 0.764, and others, confirmed the modified model fit the data well. Marital stressor, importance of children, guilt-and-blame, and social stressor showed a direct effect on perceived stress. Instead of being a factor of stress, social support was directly and positively related to self-esteem. Perceived stress and self-esteem were the two major mediators for the relationships between stressors and mental symptoms. Increase in social support and self-esteem led to decrease in mental symptoms among the infertile patients. CONCLUSIONS: The relational structures were identified and named as the Stressors Stress Symptoms Model, clinically applied to predict anxiety and depression from various stressors. Assessing sources and level of infertility-related stress and implementing culturally-sensitive counseling with an emphasis on positive personal value may assist in preventing the severity of depression and anxiety.
Assuntos
Ansiedade/psicologia , Depressão/psicologia , Infertilidade/psicologia , Autoimagem , Estresse Psicológico/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , Psicometria , Apoio Social , Inquéritos e Questionários , TaiwanRESUMO
Fermented wheat germ extract (FWGE) is a nutrient supplement and a potential antitumor ingredient for developing an integrated chemotherapy with standard chemotherapeutic drugs for treating ovarian cancer patients. In this study, we evaluated the tumor suppression efficiency of FWGE in human ovarian carcinoma cells, SKOV-3 and ES-2, and found the half-maximal inhibitory concentrations (IC50s) to be 643.76 µg/mL and 246.11 µg/mL after 48 h of FWGE treatment. FWGE treatment also induced programmed cell death by activating the caspase-7 cleavage in both SKOV-3 and ES-2 cells, but only caspase-3 and poly(adenosine diphosphate-ribose) polymerase cleavages were activated in SKOV-3 cells. Moreover, FWGE exhibited combination drug effects with cisplatin and docetaxel in SKOV-3 and ES-2 cells by enhancing the cytotoxicity of both drugs. In conclusion, we found that FWGE not only suppressed cell growth but also induced caspase-3-related and caspase-7-related cell death in human ovarian carcinoma cells. FWGE treatment further enhanced the cytotoxicity of cisplatin and docetaxel, suggesting that FWGE is a potential ingredient in the development of adjuvant chemotherapy with cisplatin or docetaxel for treating ovarian cancer patients.
RESUMO
OBJECTIVE: To investigate the efficacy of the PolScope on imaging the spindle morphology in oocytes at the metaphase II stage before vitrification and after thawing. DESIGN: In vitro study. SETTING: University infertility clinic and academic research laboratory. INTERVENTION(S): Oocytes at the metaphase II stage that were obtained from superovulating mice were vitrified and then thawed. MAIN OUTCOME MEASURE(S): Morphological features of the spindle in oocytes were evaluated by both the PolScope and immunofluorescent staining. RESULT(S): Using the PolScope, the morphological features of the spindle of intact thawed oocytes were undetected by 3 hours of thawing in only 25% of cases. Most of the spindle images were recognized during the first hour of observation. Additionally, the statistical analysis of agreement of spindle morphology by both the PolScope and fluorescent staining showed a weighted Kappa value of 0.70, indicating good agreement. Oocytes with good spindle morphology verified by the PolScope before vitrification had a higher survival rate of intact oocytes after thawing compared with those with poor or undetected spindle images. CONCLUSION(S): The morphological features of the spindle in oocytes evaluated by the PolScope before freezing and after thawing are significantly correlated with those assessed by immunofluorescent staining after fixation. With the assistance of the PolScope, thawed oocytes with good spindle morphology can be verified and selected for further manipulation without fixation and staining.
Assuntos
Citoesqueleto/ultraestrutura , Meiose , Oócitos/citologia , Animais , Mapeamento Cromossômico , Criopreservação , Feminino , Metáfase , Camundongos , Camundongos Endogâmicos ICR , Microscopia de Fluorescência , Oócitos/ultraestrutura , Tubulina (Proteína)/análiseRESUMO
Significant follicle loss from frozen ovarian grafts is unavoidable. The authors evaluated the protective effects of the antiapoptotic agent sphingosine-1-phosphate (S1P) on vitrified ovarian grafts. Three-week-old sexually immature female FVB mice were divided into 4 groups, fresh, control without S1P, 0.5 mmol/L S1P, and 2 mmol/L S1P. The ovaries were pretreated with S1P for 1 hour and then cryopreserved by modified vitrification. The frozen-thawed ovaries were autotransplanted under the back muscles of mice for 10 days. Expression of apoptosis-related genes encoding caspase 3 and c-Myc was analyzed in the vitrified ovaries and 10 days after transplantation using real-time quantitative polymerase chain reaction. To quantify the ovarian reserve, anti-Müllerian hormone (AMH) levels and follicles were measured in the 10-day vitrified ovarian grafts. Caspase 3 and c-Myc messenger RNA did not differ significantly in the 4 groups after vitrification but was significantly upregulated in the control group after transplantation. The AMH levels and primordial follicle pool were significantly higher in the S1P-treated groups than in the control group but lower than that in the fresh group. The S1P protects vitrified ovarian grafts from ischemic reperfusion injury rather than from vitrification-associated process.