RESUMEN

OBJECTIVES: This study aimed to identify the characteristics of menopausal symptoms among Japanese and Chinese women and to determine the correlation between menopausal symptoms and self-efficacy. METHODS: We surveyed 40- to 59-year-old women, 329 of whom were from an urban area in Northwest China (Xi'an) and 310 were from an urban area in Western Japan (Ehime), using a menopausal symptoms inventory and a self-efficacy scale. Comparison analysis was conducted among pre-, peri-, and postmenopausal status, within and between the two cultural groups. Following a two-way ANOVA, multiple comparisons were performed using the Tukey-Kramer test. The correlation between severity of menopause symptoms and self-efficacy scores was evaluated using canonical correlation analysis. RESULTS: The most frequently reported symptoms were fatigue (93.6%) among Japanese women and memory loss (76.6%) among Chinese women. Japanese women showed significantly higher severity scores across all factors than Chinese, sexual function: 19.58 (SE = 0.73) versus 15.04 (SE = 0.67); mental health condition: 35.44 (SE = 1.15) versus 27.12 (SE = 0.95); interpersonal anxiety: 27.45 (SE = 0.95) versus 21.92 (SE = 0.86); autonomic balance: 42.76 (SE = 1.27) versus 35.75 (SE = 1.17); other subjective symptoms: 39.68 (SE = 1.20) versus 33.07 (SE = 1.12) in the premenopausal group (P < 0.01); and mental health conditions 35.14 (SE = 1.41) versus 29.60 (SE = 1.25), interpersonal anxiety: 27.34 (SE = 1.18) versus 20.79 (SE = 1.02), autonomic balance factors: 45.81 (SE = 1.79) versus 38.05 (SE = 1.67) in the postmenopausal group (P < 0.01). No significant differences of the factors among menopausal stages within Japanese women were found. Among Chinese women, peri- and postmenopausal women showed significantly higher severity scores on sexual function, while perimenopausal women scored higher on mental health conditions and autonomic balance factors (P < 0.01). A negative correlation was found between menopausal symptoms and self-efficacy among both Japanese and Chinese women (P < 0.01). CONCLUSIONS: Japanese women reported more severe symptoms compared with their Chinese counterparts, and for Chinese women, symptoms might be specifically associated with menopausal status. Menopausal experience is associated with self-efficacy and vice versa.

Asunto(s)

Análisis de Correlación Canónica , Menopausia , Adulto , Pueblo Asiatico , Femenino , Humanos , Japón/epidemiología , Persona de Mediana Edad , Encuestas y Cuestionarios

RESUMEN

BACKGROUND: Acetaminophen (APAP) overdose is the common cause of acute liver failure (ALF) due to the oxidative damage of multiple cellular components. This study aimed to investigate whether plasma membrane vesicles (PMVs) from human umbilical cord mesenchymal stem cells (hUCMSCs) could be exploited as a novel stem cell therapy for APAP-induced liver injury. METHODS: PMVs from hUCMSCs were prepared with an improved procedure including a chemical enucleation step followed by a mechanical extrusion. PMVs of hUCMSCs were characterized and supplemented to hepatocyte cultures. Rescue of APAP-induced hepatocyte damage was evaluated. RESULTS: The hUCMSCs displayed typical fibroblastic morphology and multipotency when cultivated under adipogenic, osteogenic, or chondrogenic conditions. PMVs of hUCMSCs maintained the stem cell phenotype, including the presence of CD13, CD29, CD44, CD73, and HLA-ABC, but the absence of CD45, CD117, CD31, CD34, and HLA-DR on the plasma membrane surface. RT-PCR and transcriptomic analyses showed that PMVs were similar to hUCMSCs in terms of mRNA profile, including the expression of stemness genes GATA4/5/6, Nanog, and Oct1/2/4. GO term analysis showed that the most prominent reduced transcripts in PMVs belong to integral membrane components, extracellular vesicular exosome, and extracellular matrix. Immunofluorescence labeling/staining and confocal microscopy assays showed that PMVs enclosed cellular organelles, including mitochondria, lysosomes, proteasomes, and endoplasmic reticula. Incorporation of the fusogenic VSV-G viral membrane glycoprotein stimulated the endosomal release of PMV contents into the cytoplasm. Further, the addition of PMVs and a mitochondrial-targeted antioxidant Mito-Tempo into cultures of APAP-treated HepG2 cells resulted in reduced cell death, enhanced viability, and increased mitochondrial membrane potential. Lastly, this study demonstrated that the redox state and activities of aminotransferases were restored in APAP-treated HepG2 cells. CONCLUSIONS: The results suggest that PMVs from hUCMSCs could be used as a novel stem cell therapy for the treatment of APAP-induced liver injury.

Asunto(s)

Acetaminofén , Células Madre Mesenquimatosas , Acetaminofén/toxicidad , Diferenciación Celular , Membrana Celular , Tratamiento Basado en Trasplante de Células y Tejidos , Células Hep G2 , Humanos , Cordón Umbilical

RESUMEN

BACKGROUND AND PURPOSE: At the early stage of Alzheimer's disease (AD), the accumulation of ß-amyloid (Aß) oligomers disturbs intracellular Ca(2+) homeostasis and disrupts synaptic plasticity of brain neurons. Prevention of Aß-induced synaptic failure remains an unsolved problem for the treatment of AD. Here, the effects of 2-aminoethoxydiphenyl borate (2-APB), a non-specific, but moderately potent Ca(2+) channel inhibitor, on Aß-induced deficit of synaptic long-term potentiation (LTP) and the underlying molecular mechanisms were explored. EXPERIMENTAL APPROACH: We used hippocampal slices and primary cultures of hippocampal neurons from C57BL/6 mice. Methods applied in our study included electrophysiological recording, membrane protein extraction, Western blot assay and Ca(2+) imaging. KEY RESULTS: 2-APB at 10 µM effectively reversed suppression by oligomeric Aß1-42 (500 nM) of LTP in hippocampal slices. 2-APB also restored phosphorylation and trafficking of the glutamate receptor subunit GluA1 in Aß-treated hippocampal slices, supporting its protective action on synaptic function. Aß-mediated abnormal neuronal [Ca(2+) ]i elevation and hyperactivation of the mitochondrial apoptotic proteins BAX, caspase-3, and glycogen synthase kinase-3ß, were blocked by 2-APB pretreatment. Moreover, the defict in long term potentiation deficit in hippocampal slices from APPswe /PS1ΔE 9 gene mutant mice was rescued by 2-APB at 10 µM. CONCLUSIONS AND IMPLICATION: These data demonstrate that 2-APB is a potentially useful chemical to protect synaptic plasticity against neurotoxic effects of Aß in AD.

Asunto(s)

Péptidos beta-Amiloides/farmacología , Compuestos de Boro/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Señalización del Calcio/efectos de los fármacos , Caspasa 3/metabolismo , Hipocampo/efectos de los fármacos , Potenciación a Largo Plazo/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Sinapsis/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animales , Células Cultivadas , Activación Enzimática , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Hipocampo/enzimología , Técnicas In Vitro , Ratones Endogámicos C57BL , Ratones Mutantes , Fosforilación , Presenilina-1/genética , Cultivo Primario de Células , Transporte de Proteínas , Receptores AMPA/efectos de los fármacos , Receptores AMPA/metabolismo , Sinapsis/enzimología , Factores de Tiempo

RESUMEN

Lung cancer is one of the most common causes of cancer-related mortality worldwide. Effective early diagnosis and targeted therapies for lung cancer to reduce incidence and mortality would benefit from a better understanding of the key molecular changes that occur from normal to malignant tumor cells during lung cancer initiation and development, but these are largely unknown. Previous studies have shown that DNA methylation, an important mechanism for the regulation of gene expression, plays a key role in lung carcinogenesis. In this study, we screened a novel methylation gene, ANKRD18A, encoding ankyrin repeat domain 18A, to determine whether it is regulated by DNA methylation in lung cancer. Methylation-specific PCR and bisulfite sequencing PCR were used to analyze gene methylation status, and real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) examined mRNA levels. Promoter hypermethylation of ANKRD18A was detected in 68.4% (26/38) of lung cancer tissues but not (0/20) in normal lung tissues (P<0.01), whereas ANKRD18A mRNA expression was significantly decreased in lung cancer tissues compared with adjacent normal tissues. In addition, we found that ANKRD18A expression was significantly decreased in 9 of 10 lung cancer cell lines. This was associated with hypermethylation of the ANKRD18A promoter region. Moreover, weak expression of ANKRD18A in methylated lung cancer cell lines increased markedly after treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine. These results suggest that ANKRD18A hypermethylation and consequent mRNA alterations might be a vital molecular mechanism in lung cancer.

Asunto(s)

Repetición de Anquirina , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Azacitidina/análogos & derivados , Azacitidina/farmacología , Metilación de ADN , Metilasas de Modificación del ADN/antagonistas & inhibidores , Decitabina , Regulación hacia Abajo , Humanos , Regiones Promotoras Genéticas

Asunto(s)

Hidroxilamina/toxicidad , Espermatozoides/efectos de los fármacos , Testículo/citología , Animales , Relación Dosis-Respuesta a Droga , Masculino , Ratas , Ratas Wistar , Testículo/efectos de los fármacos

RESUMEN

The automated micronucleus test is now accepted as a simple, objective, and accurate method for evaluating potential mutagenic effects caused by physical, chemical or biotic factors. This paper describes a single-laser flow cytometry, based on an immunomagnetic isolation technique in combination with acridine orange staining, to detect frequencies of micronucleated transferrin-receptor positive reticulocytes from human peripheral blood. Using this flow cytometric system, we detected the frequencies of micronucleated transferrin-receptor positive reticulocytes from 10 nasopharyngeal cancer patients undergoing radiotherapy and the baseline of the frequencies of micronucleated transferrin-receptor positive reticulocytes from 7 healthy donors. The results showed that the mean frequency of micronucleated transferrin-receptor positive reticulocytes from healthy donors was 0.236% and that from nasopharyngeal cancer patients before radiotherapy was 0.297%. After radiotherapy it was significantly elevated. When the cumulative dose of radiotherapy was about 20Gy, it reached a maximum of 6.905%, and then, as the cumulative dose of radiotherapy continued to increase to 30Gy, 40Gy and 50Gy, the frequency decreased to 6.258%, 5.119% and 5.007% respectively. Our results indicated that the single-laser flow cytometric system was quick, reasonable and acceptable for detecting the frequency of micronucleated transferrin-receptor positive reticulocytes from human peripheral blood.

Asunto(s)

Citometría de Barrido por Láser/métodos , Pruebas de Micronúcleos/métodos , Traumatismos por Radiación/sangre , Traumatismos por Radiación/etiología , Receptores de Transferrina/sangre , Reticulocitos/metabolismo , Reticulocitos/efectos de la radiación , Adulto , Relación Dosis-Respuesta en la Radiación , Citometría de Flujo/métodos , Humanos , Separación Inmunomagnética/métodos , Enfermedades Nasofaríngeas/sangre , Enfermedades Nasofaríngeas/radioterapia , Dosificación Radioterapéutica , Reproducibilidad de los Resultados , Reticulocitos/patología , Sensibilidad y Especificidad , Resultado del Tratamiento

RESUMEN

AIM: To explore the molecular spectra and mechanism of human hypoxanthine guanine phosphoribosyl transferase (hprt) gene mutation induced by ethyluitrosourea (ENU) and (60)Co gamma-rays. METHODS: Independent human promyelocytic leukemia cells (HL-60) mutants at the hprt locus were isolated from untreated, ethyluitrosourea (ENU) and (60)Co gamma-ray-exposed cells, respectively, and verified by two-way screening. The genetic changes underlying the mutation were determined by multiplex polymerase chain reaction (PCR) amplification and electrophoresis technique. RESULTS: With dosage increased, survival rate of plated cell reduced (in the group with dosage of ENU with 100-200 micro g/ml, P<0.01; in the group with dosage of (60)Co gamma-ray with 2-4 Gy, P<0.05) and mutational frequency increased (in the group of ENU 12.5-200.0 micro g/ml, P<0.05; in the group of (60)Co gamma-ray with 1-4 Gy, P<0.05) significantly. In the 13 spontaneous mutants analyzed, 92.3 % of mutant clones did not show any change in number or size of exon, a single exon was lost in 7.7 %, and no evidence indicated total gene deletion occurred in nine hprt exons. However, deletions were found in 79.7 % of ENU-induced mutations (62.5-89.4 %, P<0.01) and in 61.7 % of gamma-ray-induced mutations (28.6-76.5 %, P<0.01). There were deletion mutations in all 9 exons of hprt gene and the most of induced mutations were chain deletion with multiplex exons (97.9 % in gamma-ray-induced mutants, 88.1 % in ENU-induced mutants). CONCLUSION: The spectra of spontaneous mutations differs completely from that induced by EUN or (60)Co gamma-ray. Although both ENU and gamma-ray can cause destruction of genetic structure, mechanism of mutagenesis between them may be different.

Asunto(s)

Alquilantes/farmacología , Etilnitrosourea/farmacología , Rayos gamma , Hipoxantina Fosforribosiltransferasa/genética , Mutación , Reacción en Cadena de la Polimerasa/métodos , Células HL-60 , Humanos , Hipoxantina Fosforribosiltransferasa/efectos de los fármacos , Hipoxantina Fosforribosiltransferasa/efectos de la radiación