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UTX (also known as KDM6A) encodes a histone H3K27 demethylase and is an important tumour suppressor that is frequently mutated in human cancers1. However, as the demethylase activity of UTX is often dispensable for mediating tumour suppression and developmental regulation2-8, the underlying molecular activity of UTX remains unknown. Here we show that phase separation of UTX underlies its chromatin-regulatory activity in tumour suppression. A core intrinsically disordered region (cIDR) of UTX forms phase-separated liquid condensates, and cIDR loss caused by the most frequent cancer mutation of UTX is mainly responsible for abolishing tumour suppression. Deletion, mutagenesis and replacement assays of the intrinsically disordered region demonstrate a critical role of UTX condensation in tumour suppression and embryonic stem cell differentiation. As shown by reconstitution in vitro and engineered systems in cells, UTX recruits the histone methyltransferase MLL4 (also known as KMT2D) to the same condensates and enriches the H3K4 methylation activity of MLL4. Moreover, UTX regulates genome-wide histone modifications and high-order chromatin interactions in a condensation-dependent manner. We also found that UTY, the Y chromosome homologue of UTX with weaker tumour-suppressive activity, forms condensates with reduced molecular dynamics. These studies demonstrate a crucial biological function of liquid condensates with proper material states in enabling the tumour-suppressive activity of a chromatin regulator.
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Diferenciación Celular , Cromatina , Genes Supresores de Tumor , Histona Demetilasas/genética , Animales , Proteínas de Unión al ADN/metabolismo , Células Madre Embrionarias/citología , Células HEK293 , Humanos , Proteínas Intrínsecamente Desordenadas/genética , Ratones , Proteínas de Neoplasias/metabolismo , Procesamiento Proteico-Postraduccional , Células THP-1RESUMEN
Objective: To investigate sexual function stratified according to four clinical phenotypes of polycystic ovary syndrome (PCOS) and its association with clinical and quality of life parameters, and to compare these with healthy controls in Chinese women with PCOS. Methods: A cross-sectional study was designed in 1000 PCOS women and 500 control women aged 18-45 years. PCOS women were grouped into four clinical phenotypes according to the Rotterdam Criteria. FSFI (Female Sexual Function Index), SF-12 (the 12-item short form health survey) and clinical and hormonal characteristics likely to affect sexual function were determined. Results: 809 PCOS women and 385 control women with complete parameters were evaluated after screening. Phenotype A had a lower total FSFI mean score (23.14 ± 3.22) compared with phenotype D and control group (p < 0.05). The control group had the highest total FSFI mean score (24.98 ± 3.78). For the percentage at risk of sexual dysfunction, phenotype A (87.5%) and phenotype B (82.46%) had a higher risk of female sexual dysfunction (FSD) than that in phenotype C (75.34%), phenotype D (70.56%) and control group (61.30%) (p < 0.05). SF-12 mental domain scores were significantly lower in phenotypes A and B compared with phenotypes C and control group (p < 0.05). Infertility treatment, bioavailable testosterone, psychological factors, age and waist circumference presented negative correlation with female sexual function. Conclusions: The risk of FSD in PCOS women seemed to be associated with PCOS clinical phenotypes. The classical PCOS phenotype with oligo-ovulation and hyperandrogenism had a higher risk of sexual dysfunction.
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Síndrome del Ovario Poliquístico , Disfunciones Sexuales Fisiológicas , Femenino , Humanos , Estudios Transversales , Pueblos del Este de Asia , Fenotipo , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/epidemiología , Síndrome del Ovario Poliquístico/diagnóstico , Calidad de Vida , Disfunciones Sexuales Fisiológicas/etiologíaRESUMEN
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that usually begins during adolescence. Patients may have severe metabolic disorders. OBJECTIVE: To investigate the levels of visfatin and apelin in adolescent girls with PCOS and to explore the importance of visfatin and apelin in glucose and lipid metabolism. METHODS: A total of 88 girls (aged 12-20 years) were prospectively and consecutively recruited during two years for the PCOS group (n = 44) and the control group (n = 44). Serum visfatin, apelin and other metabolic parameters were measured. Receiver operator characteristics (ROC) curve analysis was performed to reveal the diagnostic potential. RESULTS: Visfatin, apelin and indicators of glucose and lipid-metabolism were not different for PCOS patients compared to control. However, insulin resistance (IR) in the PCOS-group was more frequent (p < 0.05). Visfatin in non-IR patients was higher than in IR-patients in the PCOS-group (p < 0.05). However, there was no difference in apelin levels between IR and non-IR patients in the PCOS-group (p > 0.05). ROC-curve analyses demonstrated that the optimal value of visfatin for predicting IR in PCOS-patients was 7.14 ng/mL, with 78.1% sensitivity and 68.7% specificity. In the PCOS-group, visfatin was positively correlated with high density lipoprotein cholesterol (HDL-C), and negatively correlated with HOMA-IR, apolipoprotein B (Apo-B), cholesterol (CHO), low density lipoprotein cholesterol (LDL-C) and CHO/HDL-C ratio (p < 0.05). Apelin had no correlation with all indices (p > 0.05). CONCLUSIONS: Higher visfatin levels may prevent IR in adolescent PCOS patients, showing a positive predictive value for IR and also reflecting a beneficial effect on lipids. It is a possible protective factor at certain stages of metabolic syndrome.
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Resistencia a la Insulina , Síndrome del Ovario Poliquístico , Femenino , Humanos , Adolescente , Apelina , Nicotinamida Fosforribosiltransferasa , GlucosaRESUMEN
OBJECTIVE: To evaluate whether Zi Gui Nv Zhen capsules (ZGNZC) can increase the fertility rate of Chinese women with infertility due to thin endometrium. METHODS: Prospective, randomized, open-labeled 3-monthly study; 104 patients (aged 20-40 years) receiving either ZGNZC (experimental group, n = 55) or not (control group, n = 49). Main outcomes: thickness/type of the endometrium during ovulation and pregnancy rate. Between-group analysis (A) compares the experimental vs. control group, and within-group analysis (B) compares data at baseline and after study in the experimental group. RESULTS: (A) Between-group-analysis: Patients with ZGNZC had a higher endometrium thickness (0.8 ± 0.27 vs. 0.68 ± 0.10; p < .05) and higher type A endometrium rates (34.2% vs. 13.2%; p < .05) than the control group. Pregnancy rates were higher in the experimental than in the control group (43.6% vs. 22.4%; p < .05). (B) Within-group-analysis: ZGNZC increased endometrium thickness (0.58 ± 0.13 vs. 0.87 ± 0.24 vs. 0.83 ± 0.26 vs. 0.80 ± 0.27), and type A endometrium rates (10.9% vs. 60.0% vs. 49.0% vs. 34.2%) (all p < .05). Univariate analysis of pregnancy with other study parameters showed positive and significant correlations between pregnancy and administration of ZGNZC (p < .05). All hepato-renal biomarkers remained within the norm. There were no adverse events. CONCLUSIONS: In infertile women with thin endometrium who wish to conceive, two months' application of ZGNZC can improve endometrial properties and proliferation, which is necessary for a healthy pregnancy, and increase the clinical pregnancy rate in our prospective randomized observational study.
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Infertilidad Femenina , Ligustrum , Embarazo , Humanos , Femenino , Infertilidad Femenina/tratamiento farmacológico , Índice de Embarazo , Estudios Prospectivos , Medicina Tradicional China , EndometrioRESUMEN
Plant invasions profoundly impact both natural and managed ecosystems, and removal of the invasive plants addresses only part of the problem of restoring impacted areas. The rehabilitation of diverse communities and their ecosystem functions following removal of invasive plants is an important goal of ecological restoration. Arthropod assemblages and trophic interactions are important indicators of the success of restoration, but they have largely been overlooked in saltmarshes. We determined how arthropod assemblages and trophic interactions changed with the invasion of the exotic plant Spartina alterniflora and with the restoration of the native plant Phragmites australis following Spartina removal in a Chinese saltmarsh. We investigated multiple biotic and abiotic variables to gain insight into the factors underlying the changes in arthropod assemblages and trophic structure. We found that although Spartina invasion had changed arthropod diversity, community structure, feeding-guild composition, and the diets of arthropod natural enemies in the saltmarsh, these changes could be reversed by the restoration of native Phragmites vegetation following removal of the invader. The variation in arthropod assemblages and trophic structure were critically associated with four biotic and abiotic variables (aboveground biomass, plant density, leaf N, and soil salinity). Our findings demonstrate the positive effects of controlling invasive plants on biodiversity and nutrient cycling and provide a foundation for assessing the efficacy of ecological restoration projects in saltmarshes.
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OBJECTIVE: (1) To investigate anti-Mullerian-hormone (AMH) in adolescents with polycystic ovary syndrome (PCOS) compared to age-matched girls without PCOS; (2) to determine whether AMH is a valuable marker for diagnosing PCOS and to explore the best cutoff value in adolescents; (3) using a multivariate predictive model for the diagnosis of PCOS. METHODS: Ninety girls (aged 10-20 years) recruited during two years for the PCOS-group (n = 45) or control-group (n = 45). PCOS diagnostic criteria according guidelines of the Endocrinology Expert Group, Obstetrics/Gynecology Branch of the Chinese Medical Association. Serum AMH and other sex hormones were measured. Logistic regression analysis to estimate the odds ratio of AMH and other variables for the diagnosis of PCOS. Receiver operator characteristics (ROC) curve analysis was performed to reveal the diagnostic potential. RESULTS: (A) AMH was significantly higher in PCOS patients than in controls (10.21 ± 5.85 ng/ml vs. 4.31 ± 2.84 ng/ml, p < .001). In PCOS-group, total testosterone (TT), free testosterone (FT) and biologically active testosterone (BioT) were significantly higher than in controls (p < .001). (B) Logistic regression suggests that AMH and TT are correlated with the diagnosis of PCOS (p < .05). (C) ROC curve analyses demonstrated that the optimal value of AMH for predicting PCOS was 6.32 ng/mL, with 69.8% sensitivity and 80.5% specificity. Furthermore, AMH combined with TT can provide 83.7% sensitivity and 80.5% specificity for diagnosing PCOS in adolescents. CONCLUSIONS: AMH may be a useful biomarker for the diagnosis of PCOS in Chinese adolescent girls. A cutoff value of 6.32 ng/mL best discriminated between PCOS patients and controls. Besides AMH a multivariate predictive model should include TT.
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Hormona Antimülleriana , Síndrome del Ovario Poliquístico , Adolescente , Adulto , Biomarcadores , Niño , China , Femenino , Humanos , Síndrome del Ovario Poliquístico/diagnóstico , Embarazo , Testosterona , Adulto JovenRESUMEN
OBJECTIVE: To evaluate for the first time whether Zi Gui Nv Zhen® capsules (ZGNZC), until now used in traditional Chinese medicine (TCM) for menopausal complaints, can increase the fertility of Chinese women with diminished ovarian reserve (DOR). METHODS: Prospective, randomized, open-labeled 3-monthly study; 109 DOR patients (aged 20-40 years) receiving either ZGNZC (experimental group, n = 75) or not (control group, n = 34). Main outcomes: markers for ovarian function, thickness/type of the endometrium during ovulation, and pregnancy rate. Between-group analysis (A) comparing experimental vs. control group and within-group analysis (B) comparing data at baseline and after study in each of both groups. RESULTS: (A) Between-group-analysis: patients with ZGNZC had a higher endometrium thickness (0.75 vs. 0.62; p<.05) and higher anti-Müllerian hormone (AMH, 0.50 vs. 0.40; p<.05) than control group. Pregnancy rates were higher in the experimental than the control group (26.7% vs. 14.7%; n.s.). (B) Within-group-analysis: ZGNZC decreased levels of follicle-stimulating hormone (FSH, 11.42 vs. 8.69), increased estradiol-levels (E2, 56.09 vs. 73.36), and type A endometrium rates (5.3% vs. 39.7%) (all p< .05) and increased antral follicle count (AFC, 2 vs. 3). All hepato-renal biomarkers remained within the norm. The tolerability was good. There were no adverse events. CONCLUSIONS: In women with DOR who wish to conceive, three months' application of ZGNZC can improve ovarian function and oocyte quality by adjusting the neuroendocrine system, can improve endometrial properties and proliferation, necessary for a healthy pregnancy, and increased the clinical pregnancy rate in our prospective randomized observational study.
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Medicamentos Herbarios Chinos/administración & dosificación , Preservación de la Fertilidad/métodos , Reserva Ovárica/efectos de los fármacos , Hormona Antimülleriana/sangre , Medicamentos Herbarios Chinos/efectos adversos , Endometrio/anatomía & histología , Endometrio/efectos de los fármacos , Endometrio/fisiología , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Medicina Tradicional China , Embarazo , Índice de Embarazo , Estudios ProspectivosRESUMEN
ABSTRACT: Space infection occurs commonly in the oral and maxillofacial region, and is usually caused by odontogenic infection, resulting in acute symptoms through the maxillofacial space. if timely, correct, and effective treatment is not provided, local infection may quickly spread through the maxillofacial space and cause serious consequences such as suffocation, intracranial infection, and chest infection. A 55-year-old man visited our hospital with obvious swelling and pain in the right maxillofacial region. Maxillofacial computed tomography images showed revealed obvious low-density shadows on the inner side of the right mandibular angle and the right neck. Unlike the usual presentation of maxillofacial space infection, no obvious flushing or fluctuation was seen in the patient's maxillofacial region due to the deep location of the infection. Blind puncture examination and incision exploration may cause unnecessary pain and trauma to the patient. Therefore, to accurately position the infection focus, the operator reconstructed the infection cavity in three-dimensional with digital technology. The puncture point and incision site were quickly determined by three-dimensional measurement and the use of the compass and straightedge construction method, thereby achieving free drainage with an accurate and minimally invasive incision. Following 1 week of routine flushing and dressing changes, the patient recovered and was discharged from hospital. To our knowledge, this is the first precise minimally invasive treatment of a maxillofacial space infection conducted with the aid of digital positioning technology.
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Tecnología Digital , Cuello , Masculino , Humanos , Persona de Mediana Edad , Drenaje , Tratamiento de Urgencia , DolorRESUMEN
Adipose-derived mesenchymal stem cells (ADSCs) are considered to be seed cells in bone tissue engineering and emerging evidence indicates that circular RNAs (circRNAs) function in the osteogenic differentiation of ADSCs. The mechanisms of osteoblastic differentiation of ADSCs from the perspective of circRNA modulation are examined in this study. First, circRNA-23525 was upregulated during osteoblastic differentiation of ADSCs. Second, overexpression of circRNA-23525 increased Runx2, ALP and OCN at both mRNA and protein levels. Alkaline phosphatase (ALP) and Alizarin Red staining indicated a similar tendency. Silencing circRNA-23525 produced the opposite effect. Bioinformatics analysis with luciferase assays confirmed that circRNA-23525 functioned as a sponge for miR-30a-3p. In the osteoblastic differentiation of ADSCs, the dynamic expression of miR-30a-3p and circRNA-23525 resulted in an opposite trend at 3, 7 and 14 days. Overexpression of circRNA-23525 downregulated miR-30a-3p and knockdown of circRNA-23525 promoted the expression of miR-30a-3p. Bioinformatics methods and luciferase assays suggested that miR-30a-3p modulated Runx2 expression by targeting 3'UTR. Knockdown of miR-30a-3p facilitated osteogenesis in ADSCs and enhancing miR-30a-3p interfered with the osteogenic process. Finally, circRNA-23525 overexpression significantly increased Runx2 expression, while co-transfection of miR-30a-3p mimics reversed it. Runx2 expression was decreased in circRNA-23525-knockdown ADSCs but expression was rescued by including the miR-30a-3p inhibitor in the osteoblastic process. ALP activity and mineralized bone matrix confirmed the function of circRNA-23525/miR-30a-3p in osteogenesis. Taken together, the current study demonstrated that circRNA-23525 regulates Runx2 expression via targeting miR-30a-3p and is thus a positive regulator in the osteoblastic differentiation of ADSCs.
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Diferenciación Celular/genética , Células Madre Mesenquimatosas/metabolismo , MicroARNs/metabolismo , Osteogénesis/genética , ARN Circular/metabolismo , Animales , Secuencia de Bases , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Regulación de la Expresión Génica , Masculino , Ratones Endogámicos C57BL , MicroARNs/genética , Modelos Biológicos , Osteoblastos/citología , Osteoblastos/metabolismo , Unión Proteica , ARN Circular/genéticaRESUMEN
In order to reveal circular RNAs (circRNAs) differential expression profiles and investigate the function and mechanism of circRNAs in the metastasis of salivary adenoid cystic carcinoma (SACC), microarray was used to detect differentially expressed circRNAs in SACC-83 and SACC-lung metastasis (LM) cell lines. Up-regulated circRNAs were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to further predict their function. Expression of candidate circRNA and microRNA (miRNA) was determined using quantitative real-time polymerase chain reaction (qRT-PCR). Constructed circRNA-miRNA-mRNA co-expression network was based on TargetScan, miRanda databases. Wound healing and transwell assays were completed to examine the effects of hsa_circRNA_001982 and miR-181a-5p on cell migration and invasion. qRT-PCR confirmed hsa_circRNA_092556, hsa_circRNA_101379, and hsa_circRNA_001982 up-regulation in SACC-LM. miR-181a-5p was down-regulated in SACC-LM and correlated with up-regulated hsa_circRNA_001982. Wound healing and transwell assays indicated that silencing hsa_circRNA_001982 inhibited the migration and invasion of the SACC-LM cells. Furthermore, over-expression of hsa_circRNA_001982 promoted the migration and invasion of SACC-83 cells. Interestingly, up-regulation or down-regulation of miR-181a-5p led to the opposite result in wound healing and transwell assays. Overall, differential expression circRNA profiles in SACC-83 and SACC-LM cells may reveal potential targets and a novel mechanism of circRNAs in the metastasis of SACC. Moreover, the interaction of hsa_circRNA_001982/miR-181a-5p is closely related to the metastasis of SACC cells.
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Biomarcadores de Tumor/metabolismo , Carcinoma Adenoide Quístico/patología , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/secundario , ARN Circular/genética , Neoplasias de las Glándulas Salivales/patología , Apoptosis , Biomarcadores de Tumor/genética , Carcinoma Adenoide Quístico/genética , Carcinoma Adenoide Quístico/metabolismo , Movimiento Celular , Proliferación Celular , Perfilación de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Invasividad Neoplásica , Pronóstico , Neoplasias de las Glándulas Salivales/genética , Neoplasias de las Glándulas Salivales/metabolismo , Células Tumorales CultivadasRESUMEN
OBJECTIVE: To assess possible risk factors for female sexual dysfunction (FSD), aiming especially at smoking in China. METHODS: Female Sexual Function Index (FSFI) for assessing FSD; 621 women (24-75 years) divided into 'group FSD' (FSFI≤ 26.55) and 'group No FSD' (FSFI > 26.55). Univariate and multivariate analysis to detect potential risk factors for FSD. RESULTS: Active smoking was the strongest risk factor after multiple adjustments (OR= 6.226, 95%CI = 1.561 â¼ 24.822), but passive smoking also was significantly associated with a risk of FSD (OR = 1.887, 95%CI = 1.092 â¼ 3.260) (p < .05). Other risk factors included age (OR = 1.040, 95%CI = 1.005 â¼ 1.076), medical comorbidities (OR= 1.688, 95%CI =1.044 â¼ 2.729), postmenopausal stage (OR= 2.021, 95%CI = 1.073 â¼ 5.717), and dissatisfied marital relations (OR= 3.771, 95%CI = 1.768 â¼ 8.045). The prevalence of FSD for smokers regarding disorders of sexual arousal, orgasm and sexual satisfaction increased in active smokers; sexual desire disorder, sexual arousal disorder and pain in secondhand smokers (p < .05). CONCLUSION: The risk of FSD was closely related to depletion of ovarian function. Active smokers had the highest risk, but passive smoking also had a significant relationship to FSD. Although female smokers are rare in China, 'husband smoking' is frequent. Thus, our results should have significant healthcare consequences.
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Disfunciones Sexuales Fisiológicas/epidemiología , Disfunciones Sexuales Psicológicas/epidemiología , Fumar/epidemiología , Contaminación por Humo de Tabaco/estadística & datos numéricos , Adulto , Anciano , China/epidemiología , Femenino , Humanos , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Disfunciones Sexuales Fisiológicas/etiología , Disfunciones Sexuales Psicológicas/etiología , Fumar/efectos adversos , Encuestas y Cuestionarios , Contaminación por Humo de Tabaco/efectos adversos , Adulto JovenRESUMEN
OBJECTIVE: To investigate the correlation between abdominal adipose tissue and lumbar bone mineral density (BMD) in different menopausal periods of Chinese women. METHODS: 230 women were included in this cross-sectional study. Subjects were divided into a perimenopausal and postmenopausal group. Lumbar BMD was measured by QCT to assess total adipose tissue (TAT), visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). The concomitant variables age, body mass index (BMI), and endocrine hormones were also considered. Multiple linear regression was used to assess the relationship between abdominal adipose tissue and BMD. RESULTS: In the perimenopausal group, Spearman correlation analysis showed that there was no significant association among TAT, SAT, VAT, and BMD (all p > .05). In the postmenopausal group, BMD was negatively correlated with TAT, SAT, and VAT. In both groups, after adjustment for age and BMI, multiple linear regression analysis showed that VAT was negatively correlated with BMD (p < .05). In contrast, there was no significant correlation with TAT, SAT, and BMD. CONCLUSIONS: High VAT volume is associated with low lumbar BMD in both perimenopausal and postmenopausal women. TAT and SAT have no significant correlation with lumbar trabecular BMD.
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Grasa Abdominal/diagnóstico por imagen , Densidad Ósea , Menopausia/fisiología , Tomografía Computarizada por Rayos X/métodos , Grasa Abdominal/patología , Adiposidad/fisiología , Adulto , Anciano , China/epidemiología , Estudios Transversales , Femenino , Humanos , Vértebras Lumbares/diagnóstico por imagen , Persona de Mediana EdadRESUMEN
Non-small cell lung cancer (NSCLC) is a malignant cancer characterized by easy invasion, metastasis and poor prognosis, so that conventional chemotherapy cannot inhibit its invasion and metastasis. Doxorubicin (DOX), as a broad-spectrum antitumour drug, cannot be widely used in clinic because of its poor targeting, short half-life, strong toxicity and side effects. Therefore, the aim of our study is to construct a kind of PFV modified DOX plus schisandrin B liposomes to solve the above problems, and to explore its potential mechanism of inhibiting NSCLC invasion and metastasis. The antitumour efficiency of the targeting liposomes was carried out by cytotoxicity, heating ablation, wound healing, transwell, vasculogenic mimicry channels formation and metastasis-related protein tests in vitro. Pharmacodynamics were evaluated by tumour inhibition rate, HE staining and TUNEL test in vivo. The enhanced anti-metastatic mechanism of the targeting liposomes was attributed to the downregulation of vimentin, vascular endothelial growth factor, matrix metalloproteinase 9 and upregulation of E-cadherin. In conclusion, the PFV modified DOX plus schisandrin B liposomes prepared in this study provided a treatment strategy with high efficiency for NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Línea Celular Tumoral , Ciclooctanos , Doxorrubicina/farmacología , Transición Epitelial-Mesenquimal , Humanos , Lignanos , Liposomas , Neoplasias Pulmonares/tratamiento farmacológico , Compuestos Policíclicos , Factor A de Crecimiento Endotelial VascularRESUMEN
Osthole (Ost) is a coumarin compound and a potential drug for Alzheimer's disease (AD). However, the effectiveness of Ost is limited by solubility, bioavailability, and low permeability of the blood-brain barrier. In this study, we constructed Ost liposomes with modified CXCR4 on the surface (CXCR4-Ost-Lips), and investigated the intracellular distribution of liposomes in APP-SH-SY5Y cells. In addition, the neuroprotective effect of CXCR4-Ost-Lips was examined in vitro and in vivo. The results showed that CXCR4-Ost-Lips increased intracellular uptake by APP-SH-SY5Y cells and exerted a cytoprotective effect in vitro. The results of Ost brain distribution showed that CXCR4-Ost-Lips prolonged the cycle time of mice and increased the accumulation of Ost in the brain. In addition, CXCR4-Ost-Lips enhanced the effect of Ost in relieving AD-related pathologies. These results indicate that CXCR4-modified liposomes are a potential Ost carrier to treat AD.
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Enfermedad de Alzheimer , Enfermedad de Alzheimer/tratamiento farmacológico , Animales , Encéfalo , Cumarinas , Liposomas , RatonesRESUMEN
OBJECTIVES: The aims of the study were to investigate female sexual dysfunction (FSD) at different reproductive stages and the effect on FSD of hormone replacement therapy (HRT). METHODS: Participants (N = 524) were divided into six groups according to the Stages of Reproductive Aging Workshop (STRAW + 10): reproductive age (R), early (ET)/late (LT) menopausal transition, early (EP)/late (LP) postmenopause and early postmenopause in women using HRT (EP-HRT; oestradiol sequentially combined with dydrogesterone). The Female Sexual Function Index (FSFI) was used to assess FSD. Univariate and multivariate logistic regression analysis was carried out to predict FSD risk factors. RESULTS: There was an increase in FSD in groups EP and LP, but not in groups R, ET and LT; most FSFI scores were lower in groups EP and LP than in groups R, ET and LT (p < .05). There was no difference in FSD between groups EP and LP, but lubrication and pain scores were higher in group EP (p < .05). The prevalence of FSD was lower in group EP-HRT; most FSFI scores were higher in group EP-HRT compared with group EP as control (p < .05). Further risk factors for FSD were identified as neutral and dissatisfied marital relations, lower educational level and smoking (p < .05). CONCLUSION: We report a clear association between deteriorating sexual function and increasing STRAW + 10 classification, suggesting the consequence of decreasing ovarian function. HRT containing 'natural hormones' was shown to have a beneficial effect on FSD. The results are reported here for the first time in Chinese women.
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Terapia de Reemplazo de Hormonas/efectos adversos , Disfunciones Sexuales Fisiológicas/tratamiento farmacológico , Disfunciones Sexuales Psicológicas/psicología , Anciano , China/epidemiología , Femenino , Humanos , Persona de Mediana Edad , Posmenopausia , Prevalencia , Disfunciones Sexuales Fisiológicas/epidemiología , Disfunciones Sexuales Fisiológicas/etnología , Disfunciones Sexuales Psicológicas/epidemiología , Encuestas y CuestionariosRESUMEN
Chemotherapy for non-small cell lung cancer (NSCLC) is far from satisfactory, mainly due to poor targeting of antitumor drugs and self-adaptations of the tumors. Angiogenesis, vasculogenic mimicry (VM) channels, migration, and invasion are the main ways for tumors to obtain nutrition. Herein, RPV-modified epirubicin and dioscin co-delivery liposomes were successfully prepared. These liposomes showed ideal physicochemical properties, enhanced tumor targeting and accumulation in tumor sites, and inhibited VM channel formation, tumor angiogenesis, migration and invasion. The liposomes also downregulated VM-related and angiogenesis-related proteins in vitro. Furthermore, when tested in vivo, the targeted co-delivery liposomes increased selective accumulation of drugs in tumor sites and showed extended stability in blood circulation. In conclusion, RPV-modified epirubicin and dioscin co-delivery liposomes showed strong antitumor efficacy in vivo and could thus be considered a promising strategy for NSCLC treatment.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Péptidos de Penetración Celular/química , Diosgenina/análogos & derivados , Epirrubicina/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Neovascularización Patológica/tratamiento farmacológico , Células A549 , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/química , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Diosgenina/administración & dosificación , Diosgenina/química , Diosgenina/farmacología , Epirrubicina/química , Epirrubicina/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Liposomas , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The Novel Defense Hypothesis predicts that introduced plants may possess novel allelochemicals which act as a defense against native generalist enemies. Here, we aim to test if the chemicals involved in allelopathy in the invasive plant Wedelia trilobata can contribute to higher resistance against generalist herbivore and pathogen enemies by comparing with its native congener W. chinensis in controlled laboratory conditions. The allelopathic effects of the leaf extract from W. trilobata on the generalist enemies were also assessed. We showed that the larvae of two moth species preferred W. chinensis over W. trilobata. The growth rate of larvae feeding on W. trilobata leaves was significantly lower than those feeding on W. chinensis leaves. When detached leaves were inoculated with phytopathogens, the infected leaf area of W. trilobata was significantly smaller than that of W. chinensis. In addition, the leaf extract of W. trilobata also effectively inhibited the growth of the larvae and the mycelial growth of the phytopathogens. Our results indicate that the defenses of invasive W. trilobata against generalist herbivore and pathogen enemies are stronger than that of its native congener, which may be attributed to the allelopathic effects. This study provides novel insights that can comprehensively link the Novel Defense, Behavioral Constraint and Enemy Release hypotheses. These combined hypotheses would explain how invasive plants escape from their natural specialist enemies, where their allelopathic chemicals may deter herbivorous insects and inhibit pathogen infection.
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Asteraceae , Wedelia , Alelopatía , Animales , Herbivoria , LarvaRESUMEN
PURPOSE: Try to apply augmented reality (AR) technique which based on visual recognition artificial marks in the treatment of unilateral Orbitozygomatic Maxillary complex fractures (OZMF), and to explore the feasibility and the application value of the AR for assisting the oral and maxillofacial surgery (OMFS) treatment. METHODS: Based on the AR application JSARToolKit developed on the web, and combining with the self-designed tooth-borne type visual recognition artificial marks to display three-dimensional (3D) image of the region of interest (ROI), virtually designed the position and direction of plate on the jaw and helped OZMF surgery. According to some results to evaluate the postoperative effects, such as imaging, occlusion, facial appearance recovery, patients' satisfaction and operation time. RESULTS: The AR achieved the 3D image of ROI in real time, satisfied information enhancement of real scene, broadened the surgeon's horizons and improved the 3D recognition ability of maxillofacial tissue. After operation, patients had no discomforts, fracture reduction were well healed through imaging examination, and the titanium plate position was consistent with the preoperative planning. What is more, patients' facial appearance and occlusal function recovered well, significantly shorten the intraoperation time. CONCLUSION: Augmented reality technology is an effective method for OZMF treatment but there are still many technical difficulties which need to be get over, and its application in maxillofacial surgery and relevant basic theories are both worth further exploring.
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Fracturas Maxilares/cirugía , Adulto , Realidad Aumentada , Femenino , Humanos , Imagenología Tridimensional/métodos , Masculino , Fracturas Maxilares/diagnóstico por imagen , Persona de Mediana Edad , Procedimientos Quirúrgicos Orales/métodos , Cirugía Asistida por Computador/métodos , Cirugía BucalRESUMEN
Tumor invasion and metastasis are the nodus of anti-tumor. Epithelial cell-mesenchymal transition is widely regarded as one of the key steps in the invasion and metastasis of breast cancer. In this study, GGP modified daunorubicin plus dioscin liposomes are constructed and characterized. GGP modified daunorubicin plus dioscin liposome has suitable particle size, narrow PDI, zeta potential of about -5 mV, long cycle effect, and enhanced cell uptake due to surface modification of GGP making the liposome could enter the inside of the tumor to fully exert its anti-tumor effect. The results of in vitro experiments show that the liposome has superior killing effect on tumor cells and invasion. In vivo results indicate that the liposome prolongs the drug's prolonged time in the body and accumulates at the tumor site with little systemic toxicity. In short, the targeted liposome can effectively inhibit tumor invasion and may provide a new strategy for the treatment of invasive breast cancer.
Asunto(s)
Neoplasias de la Mama , Daunorrubicina/química , Diosgenina/análogos & derivados , Transición Epitelial-Mesenquimal , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Diosgenina/química , Humanos , LiposomasRESUMEN
The anticancer and anti-inflammatory effects of carboxyamidotriazole (CAI) have been demonstrated in several studies, but the underlying mechanisms remain to be elucidated. This study showed that CAI caused metabolic reprogramming of pancreatic cancer cells. The inhibition of mitochondrial oxidative metabolism by CAI led to increased glutamine-dependent reductive carboxylation and enhanced glycolytic metabolism. The presence of environmental substances that affect cellular metabolism, such as glutamine and pyruvate, attenuated the anticancer efficacy of CAI. Based on the action of CAI: 1) when glutamine was removed, the NAD+/NADH ratio was decreased, the synthesis of cellular aspartate was reduced, and autophagy flux was blocked; and 2) when glycolysis was pharmacologically inhibited, the ATP level was significantly decreased, the cell viability was greatly inhibited, and the compensatory rescue effect of glutamine was eliminated. When combined with chemotherapy, cotreatment with CAI and the glycolysis inhibitor 2-deoxyglucose (2-DG) inhibited the pancreatic cancer progression after chemotherapy. As the inhibition of mitochondrial oxidative metabolism can explain several anticancer activities of CAI reported previously, including inhibition of calcium entry and induction of reactive oxygen species, we demonstrate that inhibition of mitochondrial oxidative phosphorylation may be the fundamental mechanism of CAI. The combination of CAI and 2-DG causes energy depletion in cancer cells, eliminating the rescue effect of the metabolic environment. Inhibiting pancreatic cancer progression after chemotherapy is a rational application of this metabolism-disturbing combination strategy.