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1.
Gen Hosp Psychiatry ; 91: 1-10, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39243483

RESUMEN

BACKGROUND: Late-life depression, often accompanied by cognitive impairment, poses significant clinical challenges owing to its complex etiology and diverse manifestations. While antidepressants like venlafaxine and anxiolytics such as buspirone are effective for treating depression, their effects on cognitive function remain less well-understood. With the aging population increasingly experiencing geriatric depression, there is an urgent need for innovative treatment approaches that address both depressive symptoms and cognitive impairments. OBJECTIVE: This study aimed to evaluate the clinical efficacy and safety of combined buspirone and venlafaxine therapy in elderly patients diagnosed with geriatric depression accompanied by cognitive impairment. METHODS: A 12-week, randomized controlled trial was conducted involving 170 elderly patients. Participants were randomized into two groups: one receiving venlafaxine alone (control group) and the other receiving a combination of venlafaxine and buspirone (experimental group). The primary analysis was performed using an Intent-to-Treat (ITT) approach with mixed-effects linear models to assess changes in depressive symptoms, cognitive function, and anxiety levels. A supplementary Per-Protocol (PP) analysis, utilizing repeated measures ANOVA, was also conducted. RESULTS: The ITT analysis showed that the combination therapy significantly reduced depressive symptoms, as indicated by the HAMD-17 scores (p = 0.033 at week 12). Cognitive function, as measured by MoCA scores, also improved significantly in the experimental group by week 12 (p = 0.025). However, no statistically significant differences were observed in anxiety reduction between the groups (p = 0.127). The PP analysis confirmed these findings, demonstrating consistent improvements in depressive symptoms and cognitive function, particularly in those who completed the full course of treatment. The incidence of adverse events was comparable between groups, primarily mild and manageable symptoms like dry mouth, dizziness, and fatigue. CONCLUSION: The combination of buspirone and venlafaxine was found to be effective in reducing depressive symptoms and enhancing cognitive function in elderly patients with geriatric depression. However, the long-term benefits, especially regarding anxiety reduction, require further investigation. Future studies should consider larger sample sizes, longer follow-up periods, and the inclusion of placebo controls to fully assess the efficacy and safety of this treatment approach.

2.
Mikrochim Acta ; 191(8): 488, 2024 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-39066796

RESUMEN

Hydroxyl radical (·OH) scavenging capacity (HOSC) estimation is essential for evaluating antioxidants, natural extracts, or drugs against clinical diseases. While nanozymes offer advantages in related applications, they still face limitations in activity and selectivity. In response, this work showcases the fabrication of laminarin-modulated osmium (laminarin-Os) nanoclusters (1.45 ± 0.05 nm), functioning as peroxidase-like nanozymes within a colorimetric assay tailored for rational HOSC estimation. This study validates both the characterization and remarkable stability of laminarin-Os. By leveraging the abundant surface negative charges of laminarin-Os and the surface hydroxyls of laminarin, oxidation reactions are facilitated, augmenting laminarin-Os's affinity for 3,3',5,5'-tetramethylbenzidine (TMB) (KM = 0.04 mM). This enables the laminarin-Os-based colorimetric assay to respond to ·OH more effectively than citrate-, albumin-, or other polysaccharides-based Os. In addition, experimental results also validate the selective peroxidase-like behavior of laminarin-Os under acidic conditions. Antioxidants like ascorbic acid, glutathione, tannic acid, and cysteine inhibit absorbance at 652 nm in the colorimetric platform using laminarin-Os's peroxidase-like activity. Compared with commercial kits, this assay demonstrates superior sensitivity (e.g., responds to ascorbic acid 0.01-0.075 mM, glutathione 1-15 µg/mL, tannic acid 0.5-5 µM, and monoammonium glycyrrhizinate cysteine 1.06-10.63 µM) and HOSC testing for glutathione, tannic acid, and monoammonium glycyrrhizinate cysteine. Overall, this study introduces a novel Os nanozyme with exceptional TMB affinity and ·OH selectivity, paving the way for HOSC estimation in biomedical research, pharmaceutical analysis, drug quality control, and beyond.


Asunto(s)
Bencidinas , Depuradores de Radicales Libres , Glucanos , Radical Hidroxilo , Osmio , Bencidinas/química , Colorimetría/métodos , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Glucanos/química , Radical Hidroxilo/química , Radical Hidroxilo/análisis , Osmio/química , Oxidación-Reducción , Peroxidasa/química , Peroxidasa/metabolismo
3.
Adv Healthc Mater ; 13(16): e2303548, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38507709

RESUMEN

Diabetic wounds are susceptible to bacterial infections, largely linked to high blood glucose levels (hyperglycemia). To treat such wounds, enzymes like glucose oxidase (GOx) can be combined with nanozymes (nanomaterials mimic enzymes) to use glucose effectively for purposes. However, there is still room for improvement in these systems, particularly in terms of process simplification, enzyme activity regulation, and treatment effects. Herein, the approach utilizes GOx to directly facilitate the biomineralized growth of osmium (Os) nanozyme (GOx-OsNCs), leading to dual-active centers and remarkable triple enzyme activities. Initially, GOx-OsNCs use vicinal dual-active centers, enabling a self-cascaded mechanism that significantly enhances glucose sensing performance compared to step-by-step reactions, surpassing the capabilities of other metal sources such as gold and platinum. In addition, GOx-OsNCs are integrated into a glucose-sensing gel, enabling instantaneous visual feedback. In the treatment of infected diabetic wounds, GOx-OsNCs exhibit multifaceted benefits by lowering blood glucose levels and exhibiting antibacterial properties through the generation of hydroxyl free radicals, thereby expediting healing by fostering a favorable microenvironment. Furthermore, the catalase-like activity of GOx-OsNCs aids in reducing oxidative stress, inflammation, and hypoxia, culminating in improved healing outcomes. Overall, this synergistic enzyme-nanozyme blend is user-friendly and holds considerable promise for diverse applications.


Asunto(s)
Glucosa Oxidasa , Osmio , Glucosa Oxidasa/química , Glucosa Oxidasa/metabolismo , Animales , Osmio/química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Ratones , Glucemia/metabolismo , Diabetes Mellitus Experimental , Humanos , Glucosa/metabolismo , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/metabolismo
4.
Artículo en Inglés | MEDLINE | ID: mdl-38454765

RESUMEN

OBJECTIVES: This study aimed to explore new therapeutic drugs for multiple myeloma (MM). MM is a common plasma cell malignant proliferative disease, accounting for 15% of hematological malignancies. The role of daptomycin (DAP), a potential anti-tumor drug, remains unclear in MM. In the present research, we investigated the anticancer effect of DAP in MM cell line RPMI 8226. METHODS: RPMI 8226 cells were treated with DAP (20 µM, 40 µM, and 80 µM) with 20 nM bortezomib (BZ) as a positive control. Cell function was detected using CCK8, flow cytometry, and transwell assay. RESULTS: In MM cells, DAP inhibited proliferation and induced apoptosis. The cell cycle was arrested at the G1 phase after the treatment of DAP. The migration and invasion abilities were also inhibited by DAP treatment in RPMI 8226 cells. Importantly, the mRNA and protein levels of RPS19 were downregulated in DAP-treated RPMI 8226 cells. CONCLUSION: DAP inhibited the proliferation, migration, and invasion and promoted the apoptosis of MM cells. Mechanistically, the RPS19 expression was significantly decreased in DAPtreated cells. This research provides a potential therapeutic drug for MM therapy.

5.
J Pharm Pharmacol ; 76(5): 567-578, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38271051

RESUMEN

OBJECTIVES: Accumulating evidence demonstrates that copper deficiency (CuD) is a risk factor for cardiovascular diseases, besides, fructose has been strongly linked to the development of cardiovascular diseases. However, how CuD or fructose causes cardiovascular diseases is not clearly delineated. The present study aims to investigate the mechanism of CuD or fructose on cardiac remodeling. METHODS: We established a model of CuD- or fructose-induced cardiac hypertrophy in 3-week-old male Sprague-Dawley (SD) rats by CuD diet supplemented with or without 30% fructose for 4 weeks. In vitro study was performed by treating cardiomyocytes with tetrathiomolydbate (TM) and fructose. Echocardiography, histology analysis, immunofluorescence, western blotting, and qPCR were performed. KEY FINDINGS: Our findings revealed that CuD caused noticeable cardiac hypertrophy either in the presence or absence of fructose supplement. Fructose exacerbated CuD-induced cardiac remodeling and intramyocardial lipid accumulation. Furthermore, we presented that the inhibition of autophagic flux caused by Ca2+ disturbance is the key mechanism by which CuD- or fructose-induced cardiac remodeling. The reduced expression of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) in cardiomyocytes accounts for the elevated cytoplasmic Ca2+ concentration. CONCLUSIONS: Collectively, our study suggested that fructose aggravated CuD-induced cardiac remodeling through the blockade of autophagic flux via SERCA2a decreasing-induced Ca2+ imbalance.


Asunto(s)
Cardiomegalia , Cobre , Fructosa , Miocitos Cardíacos , Ratas Sprague-Dawley , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico , Remodelación Ventricular , Animales , Fructosa/efectos adversos , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Masculino , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Ratas , Cobre/metabolismo , Cobre/deficiencia , Cardiomegalia/metabolismo , Cardiomegalia/etiología , Calcio/metabolismo , Modelos Animales de Enfermedad , Autofagia/efectos de los fármacos
6.
Taiwan J Obstet Gynecol ; 62(3): 423-428, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37188447

RESUMEN

OBJECTIVE: Placenta previa is a health issue during pregnancy when the placenta wholly or partially covers the opening of the uterus. It can result in bleeding during pregnancy or after delivery, and preterm delivery. This study aimed to investigate the risk factors correlated with poorer childbirth outcomes of placenta previa. MATERIALS AND METHODS: Between May 2019 and January 2021, pregnant women diagnosed with placenta previa in our hospital were enrolled. Outcomes were postpartum hemorrhage after childbirth, and lower Apgar score and preterm delivery of the neonate. Laboratory blood examination data preoperatively were collected from medical records. RESULTS: A total of 131 subjects were included, with a median age 31 years. Multivariate analysis showed that fibrinogen reduced risk for postpartum hemorrhage (adjusted odds ratio (aOR): 0.45, 95% confidence interval (CI): 0.26-0.79, p = 0.005). Homocysteine (aOR: 0.73, 95% CI: 0.54-0.99, p = 0.04) reduced the risk while D-dimer (aOR: 1.19, 95% CI: 1.02-1.37, p = 0.02) increased the risk for low Apgar score. Age (aOR: 0.86, 95% CI: 0.77-0.96, p = 0.005) decreased the risk but history of full-term pregnancy more than twice (aOR: 8.58, 95% CI: 2.32-31.71, p = 0.001) increased the risk for preterm delivery. CONCLUSION: The findings suggest that poorer childbirth outcomes in pregnant women with placenta previa are associated with young age, history of full-term pregnancy, and preoperative concentrations of low fibrinogen, low homocysteine and high D-dimer. This provides obstetricians adjunctive information for early screening of high-risk population and relevant treatment arrangement in advance.


Asunto(s)
Placenta Previa , Hemorragia Posparto , Nacimiento Prematuro , Recién Nacido , Embarazo , Femenino , Humanos , Adulto , Placenta Previa/epidemiología , Mujeres Embarazadas , Nacimiento Prematuro/epidemiología , Factores de Riesgo , Parto , Estudios Retrospectivos
7.
Hum Gene Ther ; 34(13-14): 616-628, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37227014

RESUMEN

Adeno-associated virus (AAV)-based gene therapy has been shown to be safe and effective in numerous animal models and clinical trials for various ophthalmic diseases. Stargardt disease (STGD1; MIM #248200) is the most common autosomal recessive macular dystrophy disease, and the most common form is caused by mutations in the ABCA4 gene, a gene with 6.8 kb coding sequence. Split intein approaches increase the capacity of dual AAV gene therapy, but at the cost of reduced protein expression, which may be insufficient to achieve a therapeutic effect. In this study, we designed various dual split intein ABCA4 vectors and showed that the efficiency of expression of full-length ABCA4 protein is dependent on combinations of types and split sites of the intein system. The most efficient vectors were identified through in vitro screening, and a novel dual AAV8-ABCA4 vector was constructed and subsequently proven to express full-length ABCA4 protein at a high level, reducing bisretinoid formation and correcting the visual function of ABCA4-knockout mice. Furthermore, we evaluated therapeutic effects of different dosages by subretinal injection in mice model. Both therapeutic effects and safety were guaranteed under the treatment of 1.00 × 109 GC/eye. These results support the optimized dual AAV8-ABCA4 approach in future clinical translation for treatment of Stargardt disease.


Asunto(s)
Degeneración Macular , Enfermedades de la Retina , Ratones , Animales , Enfermedad de Stargardt/genética , Enfermedad de Stargardt/terapia , Degeneración Macular/genética , Degeneración Macular/terapia , Terapia Genética/métodos , Ratones Noqueados , Mutación , Enfermedades de la Retina/terapia
8.
Entropy (Basel) ; 25(2)2023 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-36832686

RESUMEN

Multiscale estimation for geographically weighted regression (GWR) and the related models has attracted much attention due to their superiority. This kind of estimation method will not only improve the accuracy of the coefficient estimators but also reveal the underlying spatial scale of each explanatory variable. However, most of the existing multiscale estimation approaches are backfitting-based iterative procedures that are very time-consuming. To alleviate the computation complexity, we propose in this paper a non-iterative multiscale estimation method and its simplified scenario for spatial autoregressive geographically weighted regression (SARGWR) models, a kind of important GWR-related model that simultaneously takes into account spatial autocorrelation in the response variable and spatial heterogeneity in the regression relationship. In the proposed multiscale estimation methods, the two-stage least-squares (2SLS) based GWR and the local-linear GWR estimators of the regression coefficients with a shrunk bandwidth size are respectively taken to be the initial estimators to obtain the final multiscale estimators of the coefficients without iteration. A simulation study is conducted to assess the performance of the proposed multiscale estimation methods, and the results show that the proposed methods are much more efficient than the backfitting-based estimation procedure. In addition, the proposed methods can also yield accurate coefficient estimators and such variable-specific optimal bandwidth sizes that correctly reflect the underlying spatial scales of the explanatory variables. A real-life example is further provided to demonstrate the applicability of the proposed multiscale estimation methods.

9.
Scott Med J ; 66(3): 134-141, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34225517

RESUMEN

BACKGROUND AND AIMS: Sleep disturbances are a severe problem among patients with Alzheimer's disease (AD). By evaluating sleep quality in mild-to-moderate AD patients, this study aimed to assess the effects of multi-disciplinary team (MDT) in reducing the incidence of adverse reactions of AD patients. The reduction in the incidence of adverse reactions to predict multi-disciplinary team (MDT) treatment effects. METHODS AND RESULTS: This study included 60 mild-to-moderate AD patients with sleep problems when hospitalized in Huzhou Third Municipal Hospital. The patients were randomly distributed into two groups, routine and MDT treatments. The cognitive functions, sleep conditions, and psycho-behavioral symptoms were compared between both the groups. Cognitive function declined significantly between pretherapy and follow-up in the routine treatment group (MMSE: t = -7.961, P < 0.001; MoCA: t = -4.672, P < 0.001). There was a significant decline in drowsiness in the MDT group compared to that in the routine treatment group (χ2 = 4.320, P = 0.038). Sleep quality improved significantly during the follow-up in the MDT treatment group (t = 6.098, P < 0.001). The results of the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) among family caregivers (FCGs) demonstrated that MDT treatment could alleviate caregivers' depression (t = -2.867, P = 0.042), and routine treatment can worsen their anxiety (t = 3.258, P = 0.003). CONCLUSION: The MDT treatment method as an effective and meaningful therapy can help mitigate the suffering of patients with AD and FCGs.


Asunto(s)
Enfermedad de Alzheimer , Trastornos Mentales , Trastornos del Sueño-Vigilia , Enfermedad de Alzheimer/complicaciones , Cuidadores , Humanos , Sueño , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/etiología , Trastornos del Sueño-Vigilia/terapia
10.
Front Public Health ; 9: 674357, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34123993

RESUMEN

Uterine leiomyoma (UL), common benign tumors in women of child-bearing age, are believed to be caused mainly by Qi stagnation and blood stasis, according to a theory of traditional Chinese medicine. Curcumae Rhizoma and Sparganii Rhizoma (CRSR) is a classical herb pair that activates blood circulation to dissipate blood stasis. The purpose of this study was to explore the prevention and treatment effects of CRSR component compatibility on UL in rats. We randomly assigned adult female non-pregnant rats into three groups: a normal control (NC) group, a UL model group, and a CRSR treatment group. We administered to the UL and CRSR groups oral gavage diethylstilbestrol and injected them with progesterone (P) to establish UL for 5 weeks. The CRSR group received a CRSR medicinal solution after daily modeling. The uterus morphology of the UL group showed significantly more swelling than did that of the NC group, and we found no significant abnormalities in the morphology of the CRSR group. The pathological changes associated with UL were relieved in the CRSR group. CRSR improved the related parameters of the uterus and ovarian coefficients, significantly reducing the concentrations of P in the serum and the concentrations of estradiol, P, estrogen receptor, and P receptor in the uterus and ovary. In addition, CRSR significantly improved the abnormal blood conditions of UL, shown by decreases in plasma viscosity, the erythrocyte sedimentation rate equation K value, and erythrocyte aggregation index. Therefore, CRSR component compatibility may prevent and cure UL through the above ways.


Asunto(s)
Leiomioma , Medicina Tradicional China , Animales , Dietilestilbestrol , Femenino , Leiomioma/tratamiento farmacológico , Ratas , Rizoma , Útero
11.
J Obstet Gynaecol Res ; 47(6): 1978-1986, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33723884

RESUMEN

OBJECTIVE: To investigate the expression of Fas/FasL in human villous trophoblast cell HTR8-S/Vneo of patients with recurrent spontaneous abortion (RSA), and to explore the related function and molecular mechanism of Fas/FasL signaling pathway. METHODS: The expression levels of FasL, Fas, and E-cadherin in the villous tissues of patients with RSA and those with artificial abortion in normal pregnancy (Normal) were detected by Western blot. CCK-8, flow cytometry, and wound healing were used to detect cell proliferation, apoptosis, and reactive oxygen species (ROS) level, and cell migration ability. Quantitative reverse transcription PCR (RT-qPCR) and Western blot were used to detect the expression of mRNA and protein of Notch1, FasL, Fas, E-cadherin, PKC, Hesl, sFlt-1, VEGF. RESULTS: Compared with normal group, the protein expression of FasL, Fas, and E-cadherin in villous tissues of RSA group were increased. HTR-8/SVneo cells in the H/R group had decreased proliferation and migration, increased apoptosis, and up-regulated ROS level compared with the Control group. The activation of Fas/FasL signaling pathway promoted HTR-8/SVneo cell injury in H/R group compared with the Fas/FasL+H/R group. Further RT-qPCR and Western blot experiments revealed that the mRNA and protein expression of Notch1, PKC, and Hesl were decreased in H/R group compared with Control group, while the mRNA and protein expression levels of E-cadherin, sFlt-1, and VEGF were significantly increased. CONCLUSION: The activation of Fas/FasL signaling pathway promotes trophoblast apoptosis induced by oxidative stress. This molecular mechanism relates to the inhibition of Notch1 signaling pathway activation, and the up-regulation of E-cadherin, sFlt-1, and VEGF expression.


Asunto(s)
Aborto Habitual , Trofoblastos , Apoptosis , Proliferación Celular , Proteína Ligando Fas , Femenino , Humanos , Embarazo , Transducción de Señal , Receptor fas/genética
12.
Nanomaterials (Basel) ; 11(2)2021 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-33530292

RESUMEN

A 16-nm-Lg p-type Gate-all-around (GAA) silicon nanowire (Si NW) metal oxide semiconductor field effect transistor (MOSFET) was fabricated based on the mainstream bulk fin field-effect transistor (FinFET) technology. The temperature dependence of electrical characteristics for normal MOSFET as well as the quantum transport at cryogenic has been investigated systematically. We demonstrate a good gate-control ability and body effect immunity at cryogenic for the GAA Si NW MOSFETs and observe the transport of two-fold degenerate hole sub-bands in the nanowire (110) channel direction sub-band structure experimentally. In addition, the pronounced ballistic transport characteristics were demonstrated in the GAA Si NW MOSFET. Due to the existence of spacers for the typical MOSFET, the quantum interference was also successfully achieved at lower bias.

13.
Entropy (Basel) ; 22(12)2020 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-33266523

RESUMEN

A two-party private set intersection allows two parties, the client and the server, to compute an intersection over their private sets, without revealing any information beyond the intersecting elements. We present a novel private set intersection protocol based on Shuhong Gao's fully homomorphic encryption scheme and prove the security of the protocol in the semi-honest model. We also present a variant of the protocol which is a completely novel construction for computing the intersection based on Bloom filter and fully homomorphic encryption, and the protocol's complexity is independent of the set size of the client. The security of the protocols relies on the learning with errors and ring learning with error problems. Furthermore, in the cloud with malicious adversaries, the computation of the private set intersection can be outsourced to the cloud service provider without revealing any private information.

14.
Artículo en Inglés | MEDLINE | ID: mdl-32438611

RESUMEN

BACKGROUND: This study aimed to specify the prevalence of sedentary behavior and depression and investigate the relationship between sedentary behavior and depression among college students majoring in design. METHODS: A total of 480 undergraduate and postgraduate students majoring in design were randomly enrolled from a university in Nanjing for a questionnaire that included sociodemographic data, physical health, sedentary behavior and depression. RESULTS: Participants reported that they spent 14.93 (SD = 1.76) hours on sedentary behavior per day and most of the time occurred outside the classroom. There were 161 (39.8%) students who reported depression, with a statistical difference across grades. After adjusting for sociodemographic attributes, physical health and physical activity, binary logistic regression analysis showed that the total sedentary time and time spent on school assignments on weekends were significantly associated with depression. CONCLUSIONS: To reduce the risk of depression, students majoring in design should be encouraged to change sedentary behaviors to physical activities in their study and life, such as using non-seating postures to do school assignments, making time for more physical activities and reducing assignments on weekends.


Asunto(s)
Depresión , Ejercicio Físico , Conducta Sedentaria , Estudiantes , Estudios Transversales , Femenino , Humanos , Masculino , Instituciones Académicas , Estudiantes/psicología
15.
Biomed Pharmacother ; 109: 188-194, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30396076

RESUMEN

The aim of this study was to explore the possible mechanisms of Ficus carica leaf (FCL) extract in suppressing hepatic gluconeogenesis in diabetic mice. Diabetic mice (streptozotocin-induced) received 1 g/kg of FCL extract twice a day for 6 weeks. Fasting blood glucose levels were measured and a 2-h oral glucose tolerance test was conducted. AMP-activated protein kinase (AMPK), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), and peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) expression was examined. HepG2 hepatocytes were treated with FCL extract and an AMPK inhibitor (compound C) or agonist (AICAR), and PEPCK, G6pase, PGC-1α, AMPK, forkhead transcription factor O1 (FOXO1), and hepatic nuclear factor 4α (HNF4α) expression was determined. The results showed that FCL extract inhibited the expression of PEPCK and G6Pase in the liver of diabetic mice and HepG2 hepatocytes. FCL extract activated AMPK and decreased PGC-1α, HNF4α, and FOXO1 expression. The AMPK inhibitor attenuated those effects through inhibiting gluconeogenesis, while the AMPK agonist partially enhanced gluconeogenesis. In conclusion, FCL extract inhibits hepatic gluconeogenesis via activation of AMPK and down-regulation of gluconeogenic enzymes.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Diabetes Mellitus Experimental/enzimología , Ficus , Gluconeogénesis/fisiología , Extractos Vegetales/farmacología , Hojas de la Planta , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Activación Enzimática/fisiología , Gluconeogénesis/efectos de los fármacos , Células Hep G2 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Extractos Vegetales/aislamiento & purificación
16.
J Am Chem Soc ; 140(41): 13214-13218, 2018 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-30282454

RESUMEN

A unique approach toward the preparation of cyclohexenynone equivalents was successfully developed via oxidative dearomatization of aryne precursors, featuring multiple functionalities on the target rings. Upon activation, these in situ formed cyclohexenynone intermediates exhibit good to excellent reactivity with various trapping agents. Moreover, an unprecedented cascade was discovered with aryl allyl sulfoxides, revealing a deeper utilization of the alkyne bond by concomitantly introducing one nucleophile and two electrophiles.

17.
Braz J Med Biol Res ; 51(9): e7627, 2018 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-29972430

RESUMEN

Uterine leiomyomas (ULs) are benign monoclonal tumors that arise from the underlying myometrial tissue in the uterus. Effective therapies are still lacking because of poor understanding of the pathophysiology and epidemiology. Hence, it is urgent to establish efficient animal models to screen novel anti-UL therapies. In this study, for the first time, traditional Chinese medicine and Western medicine were combined to establish an animal model of ULs in rats. In order to evaluate the function and value of the novel model, it was compared with other models. The long-term and short-term rat models for ULs were established using progesterone and diethylstilbestrol. Rats in Qi stagnation and blood stasis group were injected with epinephrine hydrochloride and received chronic unpredictable stress for two weeks. Rats in combining disease with syndrome group (CDWSG) received not only epinephrine hydrochloride injection and chronic unpredictable stress but also progesterone and diethylstilbestrol treatment. We analyzed differences in organ coefficient, uterus size, uterine pathology, concentrations of progesterone, estradiol, progesterone receptor, estrogen receptor, expression of desmin, α-smooth muscle actin, and vimentin among the five groups. The animal model of ULs was successfully constructed by loading the rats with estrogen and progesterone. The rat model of CDWSG was more stable than other groups and the method was the most efficient.


Asunto(s)
Modelos Animales de Enfermedad , Leiomioma/inducido químicamente , Medicina Tradicional China , Neoplasias Uterinas/inducido químicamente , Animales , Dietilestilbestrol/administración & dosificación , Ensayo de Inmunoadsorción Enzimática , Epinefrina/administración & dosificación , Femenino , Inmunohistoquímica , Progesterona/administración & dosificación , Ratas , Ratas Sprague-Dawley
18.
Phytother Res ; 32(4): 741-749, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29356175

RESUMEN

Radiotherapy frequently induces failure of hematopoietic system and leads to myelosuppression. The objective of this study was to investigate the protective effect of dammarane sapogenins (DS), the hydrolysed product of the constituent ginsenosides of Panax ginseng, which are produced by gut metabolism, on radiation-induced hematopoietic injury. Mice were exposed to 3.5 Gy 60 Co γ-rays of total body radiation at a dose rate of 1.60 Gy per minute and treated with DS or granulocyte colony-stimulating factor immediately after radiation. The general condition of the mice, the peripheral blood cell counts, multiple colony forming unit (CFU) assays of hematopoietic progenitor cells, hematopoietic stem cell counts, bone marrow histology, and spleen colony forming unit counts were then investigated. Our results indicated that administration with DS could ameliorate 60 Co-irradiation induced damage and significantly increase the number of peripheral blood cells (white blood cells and platelets), 5 types of hematopoietic progenitor cells CFU (CFU-GM, CFU-E, BFU-E, CFU-Meg, and CFU-GEMM), hematopoietic stem cell (Lin- c-kit+ Scal-1+ ) numbers, and CFUs in the spleen, as well as improved bone marrow histopathology. All together, these results confirmed the enhancement of DS on hematopoiesis.


Asunto(s)
Protectores contra Radiación/farmacología , Sapogeninas/farmacología , Triterpenos/farmacología , Animales , Hematopoyesis/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Damaranos
19.
Braz. j. med. biol. res ; 51(9): e7627, 2018. graf
Artículo en Inglés | LILACS | ID: biblio-951764

RESUMEN

Uterine leiomyomas (ULs) are benign monoclonal tumors that arise from the underlying myometrial tissue in the uterus. Effective therapies are still lacking because of poor understanding of the pathophysiology and epidemiology. Hence, it is urgent to establish efficient animal models to screen novel anti-UL therapies. In this study, for the first time, traditional Chinese medicine and Western medicine were combined to establish an animal model of ULs in rats. In order to evaluate the function and value of the novel model, it was compared with other models. The long-term and short-term rat models for ULs were established using progesterone and diethylstilbestrol. Rats in Qi stagnation and blood stasis group were injected with epinephrine hydrochloride and received chronic unpredictable stress for two weeks. Rats in combining disease with syndrome group (CDWSG) received not only epinephrine hydrochloride injection and chronic unpredictable stress but also progesterone and diethylstilbestrol treatment. We analyzed differences in organ coefficient, uterus size, uterine pathology, concentrations of progesterone, estradiol, progesterone receptor, estrogen receptor, expression of desmin, α-smooth muscle actin, and vimentin among the five groups. The animal model of ULs was successfully constructed by loading the rats with estrogen and progesterone. The rat model of CDWSG was more stable than other groups and the method was the most efficient.


Asunto(s)
Animales , Femenino , Ratas , Neoplasias Uterinas/inducido químicamente , Modelos Animales de Enfermedad , Leiomioma/inducido químicamente , Medicina Tradicional China , Progesterona/administración & dosificación , Ensayo de Inmunoadsorción Enzimática , Inmunohistoquímica , Epinefrina/administración & dosificación , Ratas Sprague-Dawley , Dietilestilbestrol/administración & dosificación
20.
Shanghai Arch Psychiatry ; 26(2): 88-94, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25092954

RESUMEN

BACKGROUND: Increased serum prolactin and weight gain are common side effects of atypical antipsychotics but few studies have assessed the long-term pattern of these adverse effects. AIM: Compare the effects of risperidone and quetiapine on serum prolactin and weight over 12 months of treatment among female patients with first-episode schizophrenia. METHODS: Eighty female inpatients with first-episode schizophrenia were randomly assigned to receive risperidone (n=40) or quetiapine (n=40) for 12 months. Prolactin concentration, weight and height were measured one day before starting treatment and 1, 3, 6, 9 and 12 months after initiating treatment. Severity of symptoms was assessed at the same time periods using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Thirty-one patients in the risperidone group and 33 patients in the quetiapine group completed the 12 months of treatment. PANSS scores decreased at each follow-up assessment for both groups; the improvement was significantly greater in the risperidone group after 3 months and 6 months of treatment but by the 9th month of treatment the level of improvement in the two groups was similar. In the quetiapine group serum prolactin remained stable throughout the 12 months but in the risperidone group the serum prolactin level increased 3.5- to 5.2-fold over the one-year follow-up. Weight gain was seen in both groups, particularly during the first 3 months of treatment: 62% of the increase in BMI in both groups had occurred by the end of the 3rd month of treatment. No between-group differences in weight changes were observed. The correlation between changes in weight and changes in prolactin levels were weakly positive: rs=0.17(p=0.104) in the risperidone group and r=0.07 (p=0.862) in the quetiapine group. CONCLUSIONS: Risperidone and quetiapine had similar efficacy in the first year of treatment of first-episode schizophrenia though risperidone was more rapidly effective. Use of risperidone was associated with chronic hyperprolactinemia but this did not occur with quetiapine. Long-term use of both drugs was associated with sustained weight gain; the timing and magnitude of the weight gain is similar for the two drugs. Weight gain was not strongly related to changes in prolactin levels.

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