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1.
BMC Womens Health ; 24(1): 159, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443889

RESUMEN

OBJECTIVE: Our study aims to investigate post-abortion needs-based education via the WeChat platform for women who had intended abortion in the first trimester, whether they are using effective contraception or becoming pregnant again. DESIGN: This single hospital intervention-controlled trial used a nearly 1:1 allocation ratio. Women who had intended abortions were randomly assigned to a Wechat group (needs-based education) and a control group (Traditional education). The women's ability to use effective contraception was the main result. Whether they unknowingly became pregnant again was the second result. Another result was patient anxiousness. Before and after education, women filled out questionnaires to assess their contraception methods and anxiety. METHODS: Based on the theoretical framework of contraceptions of IBL (inquiry-based learning), post-abortion women were included in WeChat groups. We use WeChat Group Announcement, regularly sending health education information, one-on-one answers to questions, and consultation methods to explore the possibilities and advantages of WeChat health education for women after abortion. A knowledge paradigm for post-abortion health education was established: From November 2021 until December 2021, 180 women who had an unintended pregnancy and undergone an induced or medical abortion were recruited, their progress was tracked for four months, and the PAC service team monitored the women's speech, discussed and classified the speech entries and summarized the common post-abortion needs in 8 aspects. At least 2 research group members routinely extracted records and categorized the outcomes. RESULTS: Before education, there were no appreciable variations between the two groups regarding sociodemographic characteristics, obstetrical conditions, abortion rates, or methods of contraception (P > 0.05). Following education, the WeChat group had a greater rate of effective contraception (63.0%) than the control group (28.6%), and their SAS score dropped statistically more than that of the control group (P < 0.05). Following the education, there were no unwanted pregnancies in the WeChat group, whereas there were 2 in the traditional PAC group. Only 5 participants in the WeChat group and 32 in the conventional PAC group reported mild anxiety after the education.


Asunto(s)
Aborto Inducido , Embarazo , Femenino , Humanos , Escolaridad , Anticoncepción , Miedo , Educación en Salud
2.
J Environ Manage ; 361: 121258, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38815428

RESUMEN

The rising accumulation of poly(ethylene terephthalate) (PET) waste presents an urgent ecological challenge, necessitating an efficient and economical treatment technology. Here, we developed chemical-biological module clusters that perform chemical pretreatment, enzymatic degradation, and microbial assimilation for the large-scale treatment of PET waste. This module cluster included (i) a chemical pretreatment that involves incorporating polycaprolactone (PCL) at a weight ratio of 2% (PET:PCL = 98:2) into PET via mechanical blending, which effectively reduces the crystallinity and enhances degradation; (ii) enzymatic degradation using Thermobifida fusca cutinase variant (4Mz), that achieves complete degradation of pretreated PET at 300 g/L PET, with an enzymatic loading of 1 mg protein per gram of PET; and (iii) microbial assimilation, where Rhodococcus jostii RHA1 metabolizes the degradation products, assimilating each monomer at a rate above 90%. A comparative life cycle assessment demonstrated that the carbon emissions from our module clusters (0.25 kg CO2-eq/kg PET) are lower than those from other established approaches. This study pioneers a closed-loop system that seamlessly incorporates pretreatment, degradation, and assimilation processes, thus mitigating the environmental impacts of PET waste and propelling the development of a circular PET economy.


Asunto(s)
Biodegradación Ambiental , Poliésteres , Tereftalatos Polietilenos , Tereftalatos Polietilenos/química , Tereftalatos Polietilenos/metabolismo , Poliésteres/metabolismo , Poliésteres/química , Hidrolasas de Éster Carboxílico
3.
J Community Health Nurs ; : 1-9, 2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38909288

RESUMEN

We aimed to analyze the effects of exclusive breastfeeding duration on the occurrence and course of pneumonia in infants aged up to 6 months. Prospective case-control study. This study was conducted from August 2020 to August 2022 at a maternity and child health hospital in China. A total of 218 infants up to 6 months of age with pneumonia were included in the analyses. Health data were obtained using a hospitalization information system or an interview-based questionnaire. Univariate and multivariate logistic regression analyses were performed to analyze the data. The incidence of pneumonia, hospitalization duration, and costs to participants were significantly affected by the duration of exclusive breastfeeding (p < 0.01). The incidence of pneumonia among participants with different exclusive breastfeeding durations also differed significantly (p < 0.01). The shorter the duration of exclusive breastfeeding, the higher the incidence of pneumonia among infants. We found that the longer the exclusive breastfeeding duration in infants up to 6 months of age, the lower the recurrence of pneumonia, the shorter the hospital stay, and the lower the hospital costs. The rate of exclusive breastfeeding for infants up to 6 months of age should be increased as much as possible to reduce the occurrence of pneumonia and hospital costs.

4.
Nutr J ; 22(1): 27, 2023 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-37208776

RESUMEN

BACKGROUND: Fruit, vegetable, and fruit juice intake is associated with the risk of gestational diabetes mellitus (GDM). However, the conclusion is limited and conflicted. The purpose of this systematic review and meta-analysis is to investigate the association between fruit, vegetable, and fruit juice consumption and the risk of GDM. METHODS: To find relevant studies, we searched PubMed, The Cochrane Library, Web of Science, Embase, ScienceDirect, PsycINFO, CINAHL, Ovid, EBSCO, CBM, CNKI, Wanfang Data, and VIP for the report on prospective cohort studies published from inception to April 8, 2022. Summary relative risks (RR) and 95% confidence intervals (Cis) were estimated using a random-effects model. RESULTS: A total of 12 studies with 32,794 participants were included in the meta-analysis. Total fruit consumption was associated with a lower risk of GDM (RR = 0.92, 95% CI = 0.86-0.99). Whereas an increasing the consumption of vegetable, including all vegetable (RR = 0.95, 95% CI = 0.87-1.03), starchy vegetable (RR = 1.01, 95% CI = 0.82-1.26), and fruit juice (RR = 0.97, 95% CI = 0.91-1.04) was not associated with a reduction in the risk of GDM. In a dose‒response analysis of eight studies, a 3% reduction in risk of GDM for a 100 g/d increase in fruit consumption (RR = 0.97, 95% CI = 0.96-0.99). CONCLUSIONS: The findings suggest that higher fruit consumption may reduce the risk of GDM, with a 3% reduction in the risk of GDM for every 100 g/d increase in fruit intake. Higher-quality prospective studies or randomized clinical trials are required to validate the effect of different variations of fruits, vegetables, and fruit juice consumption on the risk of GDM.


Asunto(s)
Diabetes Gestacional , Verduras , Embarazo , Femenino , Humanos , Frutas , Diabetes Gestacional/epidemiología , Conducta Alimentaria , Estudios Prospectivos , Jugos de Frutas y Vegetales
5.
BMC Nurs ; 22(1): 42, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36788572

RESUMEN

AIMS: To examine the mediating effect of resilience between social support and compassion fatigue among intern nursing and midwifery students during COVID-19. BACKGROUND: Compassion fatigue has become exceedingly common among intern nursing and midwifery students, especially during the COVID-19 pandemic. Social support and resilience can help intern nursing and midwifery students control their negative emotions, reduce compassion fatigue, and increase their well-being. However, the mediating effect of resilience between social support and compassion fatigue remains unclear. DESIGN: A multicentre cross-sectional survey. METHODS: A total of 307 intern nursing and midwifery students were recruited from November 2020 to February 2021 in tertiary grade A hospitals in China. Structural equation modelling was applied to analyse the mediating effects of resilience between social support and compassion fatigue. The Social Support Rating Scale, the 10-item Connor-Davidson Resilience Scale, and the Chinese version of the Compassion Fatigue Short Scale were used to collect data. The hypothetical path model was tested by using IBM SPSS version 26.0 and AMOS version 26.0 software. RESULTS: Intern nursing and midwifery students had moderate compassion fatigue. Social support positively affected resilience (ß = 0.514, p < 0.01). Social support negatively affected compassion fatigue (ß = - 0.310, p < 0.01), while resilience negatively affected compassion fatigue (ß = - 0.283, p < 0.01). Resilience played a mediating role between social support and compassion fatigue. CONCLUSION: Social support can directly affect the compassion fatigue of intern nursing and midwifery students during COVID-19 and indirectly through resilience. Stronger resilience can reduce compassion fatigue. Accordingly, resilience-based interventions should be developed to reduce compassion fatigue.

6.
Health Care Women Int ; 44(3): 262-275, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-34346293

RESUMEN

We aimed to assess the feeding pattern and influencing factors within six weeks postpartum on exclusive breastfeeding duration among Chinese mothers. This study was conducted using 2:1 matched case-control study. Cases and controls were matched for maternal age, parity and mode of birth. A total of 210 women were included. Approximately 67.9% of women stopped exclusive breastfeeding within the first six weeks postpartum. Maternal non-exclusive breastfeeding intention, lower maternal educational level, mother-infant skin to skin contact over one hour, unsatisfied breastfeeding self-evaluation and maternal unhealthy condition within the first six weeks were risk factors for ceasing exclusive breastfeeding early.


Asunto(s)
Lactancia Materna , Madres , Lactante , Embarazo , Femenino , Humanos , Estudios de Casos y Controles , Periodo Posparto , Edad Materna
7.
Int J Legal Med ; 136(3): 841-852, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35258670

RESUMEN

OBJECTIVES: To assess the performance of knee MRI for forensic age prediction and classification for 12-, 14-, 16-, and 18-year thresholds. METHODS: The ossification stages of distal femoral epiphyses and proximal tibial epiphyses were assessed using an integrated staging system by Schmeling et al. and Kellinghaus et al. for knee 3.0T MRI with T1-weighted turbo spin-echo (T1-TSE) in sagittal orientation among 852 Chinese Han individuals (483 males and 369 females) aged 7-30 years. Regression models for age prediction were constructed and their performances were evaluated based on mean absolute deviation (MAD) values. In addition, the performances of age classification were assessed using receiver operating characteristic (ROC) analyses. RESULTS: The intra- and inter-observer agreement levels were very good (κ > 0.80). The complete fusion of those two types of epiphyses took place before 18.0 years in our study participants. The minimum MAD values were 2.51 years (distal femur) and 2.69 years (proximal tibia) in males, and 2.75 years (distal femur) and 2.87 years (proximal tibia) in females. The specificity values of constructed prediction models were all above 90% for the 12-, 14-, and 16-year thresholds, compared to the 74.8-84.6% for the 18-year threshold. Better performances of age prediction and classification were observed in males by distal femoral epiphyses. CONCLUSIONS: Ossification stages via 3.0T MRI of the knee with T1-TSE sequence using an integrated staging system could be a reliable noninvasive method for age prediction or for age classification for 12-, 14-, and 16-year thresholds, especially in males by distal femoral epiphyses. However, assessments based on the full bony fusion of the distal femoral epiphysis and proximal tibial epiphysis seemed not reliable for age classification for the 18-year threshold in the Chinese Han population.


Asunto(s)
Determinación de la Edad por el Esqueleto , Epífisis , Determinación de la Edad por el Esqueleto/métodos , China , Epífisis/diagnóstico por imagen , Femenino , Fémur/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Osteogénesis , Tibia/diagnóstico por imagen
8.
Int Wound J ; 19(6): 1309-1318, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34931460

RESUMEN

Time in range (TIR) is a novel indicator of glycaemic control that has been reported to have an association with diabetic complications. The objective of the study was to explore the association of TIR with postoperative wound healing in patients with diabetic foot ulcers (DFUs). We retrospectively analysed the data of DFU patients who had undergone surgical treatment from 2015 to 2019. A 1:1 ratio in propensity score matching (PSM) was adopted to compare patients with TIR ≥50% with those <50%. Data were summarised using chi-squared, Fisher's exact, and Mann-Whitney U tests. Patients with TIR <50% underwent a higher rate of secondary surgery within a month (P = .032) and had a longer hospital stay (P = .045) with greater hospital charges (P < .001) than the TIR ≥50% group. Multivariate analysis revealed that TIR (P = .034), Wagner score (P = .009), diabetes treatment (P = .006), and type of surgery (P = .013) were independent risk factors for secondary surgery. Additionally, patient subgroups with TIR <50% and baseline HbA1c < 7.5% (P = .025), albumin level ≥ 30 g/L (P = .039), HDL < 1.16 (P = .021), or Wagner score ≥ 3 (P = .048) also experienced a higher incidence of secondary surgery. TIR was correlated with postoperative wound healing in patients with DFUs. Strict glycaemic targets should be established for surgical patients.


Asunto(s)
Diabetes Mellitus , Pie Diabético , Albúminas , Pie Diabético/etiología , Hemoglobina Glucada , Humanos , Estudios Retrospectivos , Cicatrización de Heridas
9.
Biochem Biophys Res Commun ; 569: 1-9, 2021 09 10.
Artículo en Inglés | MEDLINE | ID: mdl-34216991

RESUMEN

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor without curable therapy. Surgical resection remains the first choice of patients with GBM but tumors relapse rapidly even combined with conventional chemoradiotherapy. The mechanism of GBM rapid recurrence is poorly understood, which is largely due to the lack of an appropriate animal model, thus heavily impedes the improvement of postoperative therapy. Here we established a highly reproducible mouse GBM surgical model by using the syngeneic G422TN-GBM cells, which faithfully recapitulates the features of rapid recurrence of human GBM after surgery. Implanting 2 × 103-5 × 104 of G422TN-GBM cells in mouse cerebral cortex caused death in all animal within 23 days, while surgery was an effective therapy but not curable. After complete removal of visible tumors on day 5-9 of tumor growth, the tumors recurred macroscopically within 5 days accompanied by increasing infiltrative cancer foci. Mechanistically, the rapid recurrence of resected tumors was positively correlated to early Akt activation, which subsequently upregulated PD-L1/Vimentin and promoted proliferation/migration of cancer cells. In addition, environmental astrocytic activation with strong PD-L1 signal was prominent. Taken together, we provided a novel GBM surgical recurrence model for preclinical studies and suggested complicated recurring mechanisms involving in strong oncogenic signaling as well as immune inhibitory signals from both GBM cells and their neighboring astrocytes.


Asunto(s)
Antígeno B7-H1/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Vimentina/metabolismo , Animales , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/terapia , Línea Celular Tumoral , Terapia Combinada , Modelos Animales de Enfermedad , Glioblastoma/cirugía , Glioblastoma/terapia , Humanos , Estimación de Kaplan-Meier , Masculino , Ratones , Microscopía Fluorescente/métodos , Recurrencia Local de Neoplasia
10.
J Nurs Manag ; 28(4): 881-891, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32249450

RESUMEN

AIMS: To identify the level of workplace fatigue among midwives and factors influencing their fatigue. BACKGROUND: Midwives who play an important role in medical care are prone to experience workplace fatigue, which negatively affects their well-being and work quality. METHODS: A multi-centre cross-sectional study was conducted among 666 Chinese midwives from 38 hospitals in March 2019. Data were collected by four questionnaires of self-designed demographic questions, the Pittsburgh Sleep Quality Index, the Social Support Self-Rating Scale and the 14-item Fatigue Scale. Descriptive statistics, univariate analysis and multiple linear regression were used to analyse the data. RESULTS: Midwives had moderate levels of fatigue with the mean scores of physical fatigue, mental fatigue and total fatigue being 9.53, 6.25 and 15.79, respectively. Multiple linear regression results showed that sleep quality, social support, job satisfaction, occupational injuries, adverse life events, frequency of irregular meals and employment type were statistically significant factors influencing fatigue among the participants. CONCLUSIONS: Physical and mental fatigue were generally common among midwives and were affected by personal-related and work-related factors, sleep quality and social support. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse administrators have the opportunity to advocate for improved health policy under the two children rule to prevent workplace fatigue amongst midwives.


Asunto(s)
Fatiga/etiología , Enfermeras Obstetrices/psicología , Adulto , China , Estudios Transversales , Fatiga/psicología , Femenino , Humanos , Satisfacción en el Trabajo , Masculino , Persona de Mediana Edad , Psicometría/instrumentación , Psicometría/métodos , Encuestas y Cuestionarios , Lugar de Trabajo/psicología , Lugar de Trabajo/normas
11.
Neurochem Res ; 44(4): 849-858, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30635843

RESUMEN

Lack of blood or glucose supply is the most common pathological factor in the brain. To cope with such an energy stress, initiating programmed autophagic processes in neurons is required. However, the mechanisms controlling neuronal autophagy during starvation remain far from clear. Here, we report an essential role of 14-3-3γ in starvation-activated neuronal autophagic influx signaling and elucidate the underlying mechanism. Double-fluorescent immunostaining demonstrates that 14-3-3γ protein elevation is well co-localized with Beclin-1 and LC3 elevation in cortical neurons in ischemic brains. Starvation treatment activates autophagic influx and upregulates Beclin-1 and only the γ isoform of 14-3-3 in N2a cells and cultured cortical neurons. Suppressing overall 14-3-3 function by difopein overexpression or knocking-out the γ isoform of 14-3-3 is sufficient to abolish starvation-induced Beclin-1 induction and LC3 activation while overexpressing 14-3-3γ but no other 14-3-3 isoform significantly upregulate Beclin-1-LC3 signaling. Upon starvation, 14-3-3γ binds more p-ß-catenin but less Beclin-1. Finally, overexpressing 14-3-3γ reactivates ß-catenin-suppressed Beclin-1-LC3 signaling in neuronal cells. Taken together, our data reveal that starvation-induced 14-3-3γ is required for ß-catenin-Beclin-1-LC3-autophagy in starved neurons in vitro and in vivo, which may provide insights in the treatment of neurologic diseases such as stoke.


Asunto(s)
Proteínas 14-3-3/biosíntesis , Autofagia/fisiología , Beclina-1/biosíntesis , Proteínas Asociadas a Microtúbulos/biosíntesis , Neuronas/metabolismo , beta Catenina/biosíntesis , Animales , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Supervivencia Celular/fisiología , Células Cultivadas , Ratones , Ratones Endogámicos C57BL , Neuronas/patología , Regulación hacia Arriba/fisiología
13.
Biochim Biophys Acta Mol Basis Dis ; 1864(5 Pt A): 1754-1769, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29510196

RESUMEN

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor due to the lack of effective therapeutic drugs. Cancer therapy targeting programmed cell death protein 1 (PD-1) or programmed death ligand-1 (PD-L1) is of revolutionary. However, the role of intrinsic PD-L1, which determines immune-therapy outcomes, remains largely unclear. Here we demonstrated an oncogenic role of PD-L1 via binding and activating Ras in GBM cells. RNA-sequencing transcriptome data revealed that PD-L1 significantly altered gene expression enriched in cell growth/migration/invasion pathways in human GBM cells. PD-L1 overexpression and knockout or knockdown demonstrated that PD-L1 promoted GBM cell proliferation and migration in vitro and in vivo. Mechanistically, PD-L1 prominently activated epithelial mesenchymal transition (EMT) process in a MEK/Erk- but not PI3K/Akt-dependent manner. Further, we identified intracellular interactions of PD-L1 and H-Ras, which led to Ras/Erk/EMT activation. Finally, we demonstrated that PD-L1 overexpression promoted while knockdown abolished GBM development and invasion in orthotopic GBM models of rodents. Taken together, we found that intracellular PD-L1 confers GBM cell malignancy and aggressiveness via binding Ras and activating the downstream Erk-EMT signaling. Thus, these results shed important insights in improving efficacy of immune therapy for GBM as well as other malignant tumors.


Asunto(s)
Antígeno B7-H1/metabolismo , Transición Epitelial-Mesenquimal , Glioblastoma/metabolismo , Sistema de Señalización de MAP Quinasas , Animales , Antígeno B7-H1/genética , Quinasas MAP Reguladas por Señal Extracelular/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Glioblastoma/genética , Glioblastoma/patología , Humanos , Hielo , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Ratas , Ratas Sprague-Dawley
14.
Mol Pharmacol ; 92(3): 246-255, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28242743

RESUMEN

Hepatocellular carcinoma (HCC) is the fifth most common and the third most deadly malignant tumor worldwide. Hypoxia and related oxidative stress are heavily involved in the process of HCC development and its therapies. However, direct and accurate measurement of oxygen concentration and evaluation of hypoxic effects in HCC prove difficult. Moreover, the hypoxia-mediated mechanisms in HCC remain elusive. Here, we summarize recent major evidence of hypoxia in HCC lesions shown by measuring partial pressure of oxygen (pO2), the clinical importance of hypoxic markers in HCC, and recent advances in hypoxia-related mechanisms and therapies in HCC. For the mechanisms, we focus mainly on the roles of oxygen-sensing proteins (i.e., hypoxia-inducible factor and neuroglobin) and hypoxia-induced signaling proteins (e.g., matrix metalloproteinases, high mobility group box 1, Beclin 1, glucose metabolism enzymes, and vascular endothelial growth factor). With respect to therapies, we discuss mainly YQ23, sorafenib, 2-methoxyestradiol, and celastrol. This review focuses primarily on the results of clinical and animal studies.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Hipoxia de la Célula , Neoplasias Hepáticas/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/fisiología , Beclina-1/fisiología , Biomarcadores , Carcinoma Hepatocelular/tratamiento farmacológico , Globinas/fisiología , Glucosa/metabolismo , Proteína HMGB1/fisiología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/fisiología , Neoplasias Hepáticas/tratamiento farmacológico , Metaloproteasas/fisiología , Proteínas del Tejido Nervioso/fisiología , Neuroglobina , Oxígeno/análisis
15.
Biochem Biophys Res Commun ; 488(1): 33-39, 2017 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-28476618

RESUMEN

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a median survival time of only 14 months after treatment. It is urgent to find new therapeutic drugs that increase survival time of GBM patients. To achieve this goal, we screened differentially expressed genes between long-term and short-term survived GBM patients from Gene Expression Omnibus database and found gene expression signature for the long-term survived GBM patients. The signaling networks of all those differentially expressed genes converged to protein binding, extracellular matrix and tissue development as revealed in BiNGO and Cytoscape. Drug repositioning in Connectivity Map by using the gene expression signature identified repaglinide, a first-line drug for diabetes mellitus, as the most promising novel drug for GBM. In vitro experiments demonstrated that repaglinide significantly inhibited the proliferation and migration of human GBM cells. In vivo experiments demonstrated that repaglinide prominently prolonged the median survival time of mice bearing orthotopic glioma. Mechanistically, repaglinide significantly reduced Bcl-2, Beclin-1 and PD-L1 expression in glioma tissues, indicating that repaglinide may exert its anti-cancer effects via apoptotic, autophagic and immune checkpoint signaling. Taken together, repaglinide is likely to be an effective drug to prolong life span of GBM patients.


Asunto(s)
Carbamatos/farmacología , Carbamatos/uso terapéutico , Glioblastoma/tratamiento farmacológico , Piperidinas/farmacología , Piperidinas/uso terapéutico , Animales , Carbamatos/administración & dosificación , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Glioblastoma/metabolismo , Glioblastoma/patología , Humanos , Ratones , Ratones Endogámicos C57BL , Piperidinas/administración & dosificación , Relación Estructura-Actividad , Células Tumorales Cultivadas
16.
Biochem Biophys Res Commun ; 494(1-2): 165-172, 2017 12 09.
Artículo en Inglés | MEDLINE | ID: mdl-29037814

RESUMEN

Piperlongumine (PL), a natural alkaloid isolated from longer pepper plants, is recently found to be a potent selective anti-cancer compound. We first tested its anti-cancer effects on bladder cancer, the fifth most common and aggressive cancer worldwide, to further explore the therapeutic spectrum and molecular mechanisms of PL. PL significantly suppressed bladder cancer cell proliferation, the transition of G2/M phase to next phase, migration/invasion in vitro and bladder cancer growth/development in vivo. PL markedly elevated reactive oxygen species (ROS) and the administration of antioxidants abolished PL induced cell proliferation inhibition, G2/M phase arrest and migration suppression on bladder cancer cells. In vivo studies demonstrated that PL inhibited epithelial mesenchymal transition with profoundly decreased level of Slug, ß-catenin, ZEB1 and N-Cadherin. Further, we first reported PL effects on cytoskeleton with prominently reduced lamellipodia formation and decreased F-actin intensity in bladder cancer cells. Taken together, our results first revealed that PL suppressed bladder cancer proliferation and migration in vivo and in vitro, suggesting novel mechanism underlying PL's anti-cancer effect and providing a new anticancer drug strategy for bladder cancer therapy.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Dioxolanos/farmacología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Actinas/metabolismo , Alcaloides/farmacología , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica/prevención & control , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Neurochem Res ; 42(8): 2354-2362, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28424948

RESUMEN

Mammalian 14-3-3 isoforms exist predominantly in the brain and are heavily involved in neurological diseases. However, the isoform-specific role of 14-3-3 proteins in the brain remains largely unclear. Here, we investigated the role of 14-3-3 isoforms in rat brains after transient middle cerebral artery occlusion and reperfusion. 14-3-3ß, η, γ and ζ but not ε or τ were selectively upregulated in cerebral cortical neurons after ischemia-reperfusion (I/R). Selectively, 14-3-3ß, γ and ζ were translocated from cytoplasm into the nuclei of neurons after I/R. 14-3-3 bound to p65 and suppressed p65 expression in N2a cells. In the brain, 14-3-3 could either colocalize with p65 in the nuclei of neurons or segregate from p65 expression in cortical neurons after I/R. All evidence together suggests that 14-3-3 isoforms are differentially induced to enter into the nuclei of neurons after I/R, which might regulate NFκB signaling directly or indirectly. Since 14-3-3 proteins are essential for cell survival and NFκB is a key transcriptional factor, our data suggest that the 14-3-3/p65 signaling pathway might be a potential therapeutic target for stroke.


Asunto(s)
Proteínas 14-3-3/fisiología , Isquemia Encefálica/metabolismo , FN-kappa B/fisiología , Daño por Reperfusión/metabolismo , Transducción de Señal/fisiología , Proteínas 14-3-3/farmacología , Animales , Isquemia Encefálica/patología , Línea Celular Tumoral , Ratones , Unión Proteica/fisiología , Isoformas de Proteínas/farmacología , Isoformas de Proteínas/fisiología , Ratas , Daño por Reperfusión/patología , Transducción de Señal/efectos de los fármacos
18.
J Neurosci Res ; 93(10): 1507-18, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25711139

RESUMEN

Stroke is a leading cause of death and disability, and new strategies are required to reduce neuronal injury and improve prognosis. Ischemia preconditioning (IPC) is an intrinsic phenomenon that protects cells from subsequent ischemic injury and might provide promising mechanisms for clinical treatment. In this study, primary astrocytes exhibited significantly less cell death than control when exposed to different durations of IPC (15, 30, 60, or 120 min). A 15-min duration was the most effective IPC to protect astrocytes from 8-hr-ischemia injury. The protective mechanisms of IPC involve the upregulation of protective proteins, including 14-3-3γ, and attenuation of malondialdehyde (MDA) content and ATP depletion. 14-3-3γ is an antiapoptotic intracellular protein that was significantly upregulated for up to 84 hr after IPC. In addition, IPC promoted activation of the c-Jun N-terminal kinase (JNK), extracellular signal-related kinase (ERK)-1/2, p38, and protein kinase B (Akt) signaling pathways. When JNK was specifically inhibited with SP600125, the upregulation of 14-3-3γ induced by IPC was almost completely abolished; however, there was no effect on ATP or MDA levels. This suggests that, even though both energy preservation and 14-3-3γ up-regulation were turned on by IPC, they were controlled by different pathways. The ERK1/2, p38, and Akt signaling pathways were not involved in the 14-3-3γ upregulation and energy preservation. These results indicate that IPC could protect astrocytes from ischemia injury by inducing 14-3-3γ and by alleviating energy depletion through different pathways, suggesting multiple protection of IPC and providing new insights into potential stroke therapies.


Asunto(s)
Proteínas 14-3-3/metabolismo , Astrocitos/metabolismo , Regulación de la Expresión Génica/fisiología , Precondicionamiento Isquémico , Transducción de Señal/fisiología , Regulación hacia Arriba/fisiología , Adenosina Trifosfato/metabolismo , Animales , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Recuento de Células , Muerte Celular/efectos de los fármacos , Hipoxia de la Célula/fisiología , Células Cultivadas , Corteza Cerebral/citología , Regulación de la Expresión Génica/efectos de los fármacos , Isquemia/prevención & control , L-Lactato Deshidrogenasa/metabolismo , Malondialdehído/metabolismo , Ratones , Ratones Endogámicos ICR , Transducción de Señal/efectos de los fármacos , Factores de Tiempo
19.
Acta Pharmacol Sin ; 36(3): 362-74, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25619389

RESUMEN

AIM: To investigate the effects of piperlongumine (PL), an anticancer alkaloid from long pepper plants, on the primary myeloid leukemia cells from patients and the mechanisms of action. METHODS: Human BM samples were obtained from 9 patients with acute or chronic myeloid leukemias and 2 patients with myelodysplastic syndrome (MDS). Bone marrow mononuclear cells (BMMNCs) were isolated and cultured. Cell viability was determined using MTT assay, and apoptosis was examined with PI staining or flow cytometry. ROS levels in the cells were determined using DCFH-DA staining and flow cytometry. Expression of apoptotic and autophagic signaling proteins was analyzed using Western blotting. RESULTS: PL inhibited the viability of BMMNCs from the patients with myeloid leukemias (with IC50 less than 20 µmol/L), but not that of BMMNCs from a patient with MDS. Furthermore, PL (10 and 20 µmol/L) induced apoptosis of BMMNCs from the patients with myeloid leukemias in a dose-dependent manner. PL markedly increased ROS levels in BMMNCs from the patients with myeloid leukemias, whereas pretreatment with the antioxidant N-acetyl-L-cysteine abolished PL-induced ROS accumulation and effectively reduced PL-induced cytotoxicity. Moreover, PL markedly increased the expression of the apoptotic proteins (Bax, Bcl-2 and caspase-3) and autophagic proteins (Beclin-1 and LC3B), and phosphorylation of p38 and JNK in BMMNCs from the patients with myeloid leukemias, whereas pretreatment with the specific p38 inhibitor SB203580 or the specific JNK inhibitor SP600125 partially reversed PL-induced ROS production, apoptotic/autophagic signaling activation and cytotoxicity. CONCLUSION: Piperlongumine induces apoptotic and autophagic death of the primary myeloid leukemia cells from patients via activation of ROS-p38/JNK pathways.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Dioxolanos/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mieloide Aguda/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Antioxidantes/farmacología , Proteínas Reguladoras de la Apoptosis/metabolismo , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Activación Enzimática , Humanos , Concentración 50 Inhibidora , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Leucemia Mielógena Crónica BCR-ABL Positiva/enzimología , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Leucemia Mieloide Aguda/enzimología , Leucemia Mieloide Aguda/patología , Fosforilación , Cultivo Primario de Células , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal/efectos de los fármacos , Células Tumorales Cultivadas , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores
20.
Sheng Li Ke Xue Jin Zhan ; 45(3): 185-9, 2014 Jun.
Artículo en Zh | MEDLINE | ID: mdl-25219269

RESUMEN

Autism or autism spectrum disorders is the most common central nervous system developmental disorder in children. Until now, there is still no effective drug for autism. The latest breakthrough advance in autism study is the discovery of autism-related gene de novo mutation by the whole exon sequencing. Among multiple de novo gene mutations identified in autism, the chromodomain helicase DNA-binding protein 8 (CHD8) is the most frequently mutated gene, suggesting that CHD8 is an important candidate gene for autism. CHD8 binds to various other proteins such as p53 and beta-catenin to regulate gene expression. The discovery of autism-candidate genes provides novel molecular targets for the diagnosis and treatment of autism.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Mutación , Proteínas de Unión al ADN , Exones , Expresión Génica , Humanos , Factores de Transcripción
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