Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
Más filtros

Bases de datos
País/Región como asunto
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Front Endocrinol (Lausanne) ; 15: 1368853, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38501107

RESUMEN

Background: Monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) have been reported to combat saturated fatty acid (SFA)-induced cellular damage, however, their clinical effects on patients with metabolic diseases such as diabetes and hyperlipidemia are still controversial. Since comparative studies of the effects of these two types of unsaturated fatty acids (UFAs) are still limited. In this study, we aimed to compare the protective effects of various UFAs on pancreatic islets under the stress of SFA-induced metabolic disorder and lipotoxicity. Methods: Rat insulinoma cell line INS-1E were treated with palmitic acid (PA) with or without UFAs including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and oleic acid (OA) to determine cell viability, apoptosis, endoplasmic reticulum (ER) stress, and inflammatory. In vivo, male C57BL/6 mice were fed a 60% high-fat diet (HFD) for 12 w. Then the lard in HFD was partially replaced with fish oil (FO) and olive oil (OO) at low or high proportions of energy (5% or 20%) to observe the ameliorative effects of the UFA supplement. Results: All UFAs significantly improved PA-induced cell viability impairment in INS-1E cells, and their alleviation on PA induced apoptosis, ER stress and inflammation were confirmed. Particularly, OA had better effects than EPA, DHA, and AA on attenuating cellular ER stress. In vivo, the diets with a low proportion of UFAs (5% of energy) had limited effects on HFD induced metabolic disorder, except for a slight improved intraperitoneal glucose tolerance in obese mice. However, when fed diets containing a high proportion of UFAs (20% of energy), both the FO and OO groups exhibited substantially improved glucose and lipid metabolism, such as decrease in total cholesterol (TC), low-density lipoprotein (LDL), fasting blood glucose (FBG), and fasting blood insulin (FBI)) and improvement of insulin sensitivity evidenced by intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT). Unexpectedly, FO resulted in abnormal elevation of the liver function index aspartate aminotransferase (AST) in serum. Pathologically, OO attenuated HFD-induced compensatory hyperplasia of pancreatic islets, while this effect was not obvious in the FO group. Conclusions: Both MUFAs and PUFAs can effectively protect islet ß cells from SFA-induced cellular lipotoxicity. In particular, both OA in vitro and OO in vivo showed superior activities on protecting islets function and enhance insulin sensitivity, suggesting that MUFAs might have greater potential for nutritional intervention on diabetes.


Asunto(s)
Diabetes Mellitus , Resistencia a la Insulina , Insulinas , Humanos , Ratas , Ratones , Animales , Masculino , Ácidos Grasos Monoinsaturados , Ratones Endogámicos C57BL , Ácidos Grasos Insaturados/farmacología , Ácidos Grasos , Ácido Palmítico , Ácido Eicosapentaenoico/farmacología , Glucosa
2.
Zhongguo Zhen Jiu ; 44(2): 221-223, 2024 Feb 12.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-38373771

RESUMEN

The Elastic acupuncture needle, a set of clinical device used in randomized controlled trials of acupuncture is developed, which may potentially obtain the double-blind placebo control. This kind of acupuncture device consists of a real needle and a sham one (placebo needle) with a identical appearance. Either of the needle is composed of an integrated cap-type handle and needle body, and a sterile double-sided adhesive pad is designed on the bottom for fixation. A spring with miniature low profile is built in sham needle. During operation, the real needle can be normally inserted, while the sham one be retracted because of the elasticity generated by the pressure on the skin, but deqi can still be felt by patients whenever the force difference between the skin and the spring reaches a certain balance. The rubber pad designed in this acupuncture needle can simulate the "resistance" felt by operators during needle insertion so that the double blinding is actualized in terms of the appearance and sensations.


Asunto(s)
Terapia por Acupuntura , Acupuntura , Humanos , Sensación , Método Doble Ciego , Agujas , Ensayos Clínicos Controlados Aleatorios como Asunto
3.
Metabolites ; 13(7)2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37512536

RESUMEN

The secondary metabolites present in medicinal orchids are diverse and possess a vast array of biological activities. They represent valuable raw materials for modern pharmaceuticals and clinical medicine and have tremendous potential for future development. A systematic collation of secondary metabolites' composition and a summary of the biological activities of medicinal orchids represent a crucial step in unlocking the potential of these valuable resources in drug development. Furthermore, such information can provide essential guidance for comprehensively analyzing the pharmacological and therapeutic mechanisms of these valuable herbs in traditional Chinese herbal medicine. This review article presents an overview of the types and main biological functions of the secondary metabolites found in medicinal orchids, as well as the conventional synthesis methods for these compounds. Our aim is to provide a useful reference for future research and the drug development of secondary metabolic products of medicinal orchids.

4.
Adv Healthc Mater ; 12(23): e2300085, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37171889

RESUMEN

Helicobacter pylori (H. pylori) colonizes the stomach epithelium of half the world's population and is responsible for various digestive diseases and even stomach cancer. Vaccine-mediated protection against H. pylori infection depends primarily on the specific mucosal and T-cell responses. In this study, the synthetic lipopeptide vaccines, Hp4 (Pam2 Cys modified UreB T-cell epitope) and Hp10 (Pam2 Cys modified CagA T/B cell combined epitope), not only induce the bone marrow derived dendritic cells (BMDCs) maturation by activating a variety of pattern-recognition receptors (PRRs) such as Toll-like receptor (TLR), Nod-like receptor (NLR), and retinoic acid-inducing gene (RIG) I-like receptor (RLR), and but also stimulate BMDCs to secret cytokines that have the potential to modulate T-cell activation and differentiation. Although intranasal immunization with Hp4 or Hp10 elicits robust epitope-specific T-cell responses in mice, only Hp10 confers protection against H. pylori infection, possibly due to the fact that Hp10 also induces substantial specific sIgA response at mucosal sites. Interestingly, Hp4 elevates the protective response against H. pylori infection of Hp10 when administrated in combination, characterized by better protective effect and enhanced specific T-cell and mucosal antibody responses. The results suggest that synthetic lipopeptide vaccines based on the epitopes derived from the protective antigens are promising candidates for protection against H. pylori infection.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Animales , Ratones , Helicobacter pylori/genética , Infecciones por Helicobacter/prevención & control , Lipopéptidos/farmacología , Vacunas Bacterianas , Adyuvantes Inmunológicos , Epítopos de Linfocito T , Vacunas Sintéticas , Ratones Endogámicos BALB C
5.
Int Wound J ; 20(1): 183-190, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35778796

RESUMEN

The aim of the study was to explore the application value of manual lymphatic drainage combined with vacuum sealing drainage in axillary web syndrome (AWS) after breast cancer surgery. From 1 April 2020 to 1 June 2020, a total of 102 patients with AWS after axillary lymph node biopsy or axillary lymph node dissection in our hospital were included in this prospective study. According to the random number table method, all patients were divided into the study group (n = 51) and the control group (n = 51). The study group received the treatment of manual lymphatic drainage combined with vacuum sealing drainage, and the control group received health education and the treatment of functional training. The efficacy observation indicators included duration time to the disappearance of relevant clinical symptoms, degree of pain, angle of abduction of the affected limb, degree of upper limb disability function and quality of life. The duration time to the disappearance of cord-like nodules and tightness in the study group was both significantly shorter than that in the control group (both P < .05). In the time point of 1 and 3 months after the intervention, compared with that in the control group, the study group had a significantly lighter degree of pain, a better degree of upper limb disability function and higher quality of life (all P < .05). Manual lymphatic drainage combined with vacuum sealing drainage can shorten the disappearance time of relevant clinical symptoms, relieve the degree of pain, improve the upper limb disability function and improve the quality of life in patients with AWS.


Asunto(s)
Neoplasias de la Mama , Terapia de Presión Negativa para Heridas , Humanos , Femenino , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Drenaje Linfático Manual , Estudios Prospectivos , Calidad de Vida , Axila/cirugía , Axila/patología , Escisión del Ganglio Linfático/efectos adversos , Dolor
6.
J Trace Elem Med Biol ; 75: 127078, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36201939

RESUMEN

BACKGROUND AND AIMS: Earlier studies have reported inconsistent association between selenium (Se) and homocysteine (Hcy) levels, while no evidence could be found from Chinese population. To fill this gap, we investigated the association between blood Se and hyperhomocysteinemia (HHcy) of rural elderly population in China. METHODS: A cross-sectional study on 1823 participants aged 65 and older from four Chinese rural counties was carried out in this study. Whole blood Se and serum Hcy concentrations were measured in fasting blood samples. Analysis of covariance and restricted cubic spline models were used to examine the association between Se and Hcy levels. Logistic regression models were used to evaluate the risk of prevalent HHcy among four Se quartile groups after adjusting for covariates. RESULTS: For this sample, the mean blood Se concentration was 156.34 (74.65) µg/L and the mean serum Hcy concentration was 17.25 (8.42) µmol/L. A significant non-linear relationship was found between blood Se and serum Hcy, the association was inverse when blood Se was less than 97.404 µg/L and greater than 156.919 µg/L. Participants in the top three blood Se quartile groups had significantly lower risk of prevalent HHcy compared with the lowest quartile group. When defined as Hcy> 10 µmol/L, the odds ratios and 95% confidence interval of HHcy were 0.600 (0.390, 0.924), 0.616 (0.398, 0.951) and 0.479 (0.314, 0.732) for Q2, Q3, and Q4 Se quartile groups compared with the Q1 group, respectively. When defined as Hcy≥ 15 µmol/L, the odds ratios and 95% confidence interval of HHcy were 0.833 (0.633, 1.098) and 0.827 (0.626, 1.092), 0.647 (0.489, 0.857) for Q2, Q3, and Q4 Se quartile groups compared with Q1 group. CONCLUSIONS: Our findings suggest that higher blood Se level could be a protective factor for HHcy in the elderly.


Asunto(s)
Selenio , Anciano , Humanos , China/epidemiología , Estudios Transversales
7.
Front Cell Neurosci ; 16: 817732, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36439200

RESUMEN

Ischemic stroke is common in the elderly, and is one of the main causes of long-term disability worldwide. After ischemic stroke, spontaneous recovery and functional reconstruction take place. These processes are possible thanks to neuroplasticity, which involves neurogenesis, synaptogenesis, and angiogenesis. However, the repair of ischemic damage is not complete, and neurological deficits develop eventually. The WHO recommends acupuncture as an alternative and complementary method for the treatment of stroke. Moreover, clinical and experimental evidence has documented the potential of acupuncture to ameliorate ischemic stroke-induced neurological deficits, particularly sequelae such as dyskinesia, spasticity, cognitive impairment, and dysphagia. These effects are related to the ability of acupuncture to promote spontaneous neuroplasticity after ischemic stroke. Specifically, acupuncture can stimulate neurogenesis, activate axonal regeneration and sprouting, and improve the structure and function of synapses. These processes modify the neural network and function of the damaged brain area, producing the improvement of various skills and adaptability. Astrocytes and microglia may be involved in the regulation of neuroplasticity by acupuncture, such as by the production and release of a variety of neurotrophic factors, including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Moreover, the evidence presented indicates that acupuncture promotes neuroplasticity by modulating the functional reconstruction of the whole brain after ischemia. Therefore, the promotion of neuroplasticity is expected to become a new target for acupuncture in the treatment of neurological deficits after ischemic stroke, and research into the mechanisms responsible for these actions will be of significant clinical value.

8.
J Control Release ; 350: 122-131, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35973474

RESUMEN

Transarterial chemoembolization (TACE) with free doxorubicin-lipiodol emulsions (free DOX/L) is a favored clinical treatment for advanced hepatocellular carcinoma (HCC) patients ineligible for radical therapies; however, its inferior colloidal stability not only greatly reduces its tumor retention but also hastens drug release into blood circulation, leading to suboptimal clinical outcomes. Here, we find that disulfide-crosslinked polymersomes carrying doxorubicin (Ps-DOX) form super-stable and homogenous water-in-oil microemulsions with lipiodol (Ps-DOX/L). Ps-DOX/L microemulsions had tunable sizes ranging from 14 to 44 µm depending on the amount of Ps-DOX, were stable over 2 months storage as well as centrifugation, and exhibited nearly zero-order DOX release within 15 days. Of note, Ps-DOX induced 2.3-13.4 fold better inhibitory activity in all tested rat, murine and human liver tumor cells than free DOX likely due to its efficient redox-triggered intracellular drug release. Interestingly, transarterial administration of Ps-DOX/L microemulsions in orthotopic rat N1S1 syngeneic HCC model showed minimal systemic DOX exposure, high and long hepatic DOX retention, complete tumor elimination, effective inhibition of angiogenesis, and depleted adverse effects, significantly outperforming clinically used free DOX/L emulsions. This smart polymersome stabilization of doxorubicin-lipiodol microemulsions provides a novel TACE strategy for advanced tumors.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Animales , Antibióticos Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Disulfuros , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Emulsiones/uso terapéutico , Aceite Etiodizado/uso terapéutico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Ratones , Ratas , Agua
9.
Sci Total Environ ; 840: 156618, 2022 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-35691345

RESUMEN

Although the association between selenium (Se) and diabetes has been well-discussed in recent years, few studies have focused on the effects of long-term natural Se exposure and rarely concerned the effects of different Se biomarkers. To address this question, we carried out a 7-year longitudinal study on older adults aged over 65 and another cross-sectional study on middle-aged and older adults aged 40 and above from Chinese soil Se-deplete and Se-optimum areas. Cox proportional hazard models were used to evaluate the associations between nail Se levels and incidence risk of diabetes. Unconditional logistic regression models and analysis of variance models were used to examine the associations between serum Se levels and the prevalence risk of diabetes. The nail and serum Se levels were 0.47 ± 0.20 µg/g and 111.09 ± 55.01 µg/L for the two study populations, respectively. For both of the independent studies, higher Se levels were observed to be associated with a higher risk of diabetes and prediabetes. Compared with the Second nail Se quartile (Q2), the adjusted hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) of diabetes for Q1, Q3 and Q4 were 1.24(0.70, 2.21), 1.53(0.98, 2.39) and 1.31(0.76, 2.26), respectively, and the adjusted HRs (95 % CIs) of prediabetes were 1.47(0.77, 2.81), 1.38(0.83, 2.30), and 1.97(1.13, 3.44), respectively. Compared with the first serum Se quintile (Q1), the adjusted odds ratios (ORs) and 95 % CIs of diabetes for higher quintiles were 1.12(0.75, 1.66), 1.05(0.71, 1.57), 1.09(0.73, 1.62) and 1.51(1.02, 2.19), and the adjusted ORs (95 % CIs) of prediabetes were 1.27(0.77, 2.09), 1.70(1.05, 2.74), 1.94(1.21, 3.11) and 1.67(1.03, 2.71). Our findings consistently suggest that higher Se status is associated with a higher risk of diabetes in adults.


Asunto(s)
Diabetes Mellitus , Estado Prediabético , Selenio , Anciano , Estudios Transversales , Diabetes Mellitus/epidemiología , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Estado Prediabético/epidemiología
10.
Neural Plast ; 2021: 9926445, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34221005

RESUMEN

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disease caused by degeneration of dopaminergic neurons in the substantia nigra. Existing pharmaceutical treatments offer alleviation of symptoms but cannot delay disease progression and are often associated with significant side effects. Clinical studies have demonstrated that acupuncture may be beneficial for PD treatment, particularly in terms of ameliorating PD symptoms when combined with anti-PD medication, reducing the required dose of medication and associated side effects. During early stages of PD, acupuncture may even be used to replace medication. It has also been found that acupuncture can protect dopaminergic neurons from degeneration via antioxidative stress, anti-inflammatory, and antiapoptotic pathways as well as modulating the neurotransmitter balance in the basal ganglia circuit. Here, we review current studies and reflect on the potential of acupuncture as a novel and effective treatment strategy for PD. We found that particularly during the early stages, acupuncture may reduce neurodegeneration of dopaminergic neurons and regulate the balance of the dopaminergic circuit, thus delaying the progression of the disease. The benefits of acupuncture will need to be further verified through basic and clinical studies.


Asunto(s)
Terapia por Acupuntura , Neuronas Dopaminérgicas/fisiología , Enfermedad de Parkinson/terapia , Antiparkinsonianos/uso terapéutico , Apoptosis , Ganglios Basales/fisiopatología , Bibliometría , Ensayos Clínicos como Asunto , Terapia Combinada , Dopamina/metabolismo , Humanos , Red Nerviosa/fisiopatología , Enfermedades Neuroinflamatorias , Estrés Oxidativo , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/fisiopatología , Agregación Patológica de Proteínas , Resultado del Tratamiento , alfa-Sinucleína/análisis
11.
Aging (Albany NY) ; 13(12): 16620-16636, 2021 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-34170848

RESUMEN

Dopamine receptor, a polypeptide chain composed of 7 hydrophobic transmembrane regions, is a new and vital drug target, especially Dopamine receptor 2(D2). Targeting dopamine receptors, Dopamine receptor agonists are a class of drugs similar in function and structure to dopamine and can directly act on dopamine receptors and activate it. Clinically, Dopamine receptor agonist drugs have achieved significant therapeutic effects on prolactinoma and Parkinson's Disease. In the study, we virtually screened a series of potential effective agonists of Dopamine receptor by computer techniques. Firstly, we used the Molecular Docking (LibDock) step to screen out some molecules that can dock well with the protein. Then, analysis of toxicity prediction and ADME (adsorption, distribution, metabolism and excretion) were carried out. More precise molecular docking (CDOCKER) and 3-Dimensional Quantitative Structure-Activity Relationship Modeling Study(3D-QSAR) pharmacophore generation were implemented to research and explore these compounds' binding mechanism with Dopamine receptor. Last but not least, to assess compound's binding stabilities, we carried out a molecular dynamic analysis. As the results show, two compounds (ZINC000008860530 and ZINC000004096987) from the small molecule database (ZINC database) were potential effective agonists of Dopamine receptor. These two compounds can combine with Dopamine receptor with higher affinity and proved to be no toxic. The cell experiment showed that two compounds could inhibit the proliferation and PRL secretion of MMQ cells (pituitary tumor cells). Thus, this study provided valuable information about Dopamine receptor agonist-based drug discovery. So, this study will benefit patients with prolactinoma and Parkinson's disease a lot.


Asunto(s)
Productos Biológicos/química , Productos Biológicos/farmacología , Agonistas de Dopamina/química , Agonistas de Dopamina/farmacología , Simulación del Acoplamiento Molecular , Receptores Dopaminérgicos/química , Productos Biológicos/análisis , Productos Biológicos/toxicidad , Bromocriptina/química , Bromocriptina/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Agonistas de Dopamina/análisis , Agonistas de Dopamina/toxicidad , Evaluación Preclínica de Medicamentos , Humanos , Enlace de Hidrógeno , Ligandos , Simulación de Dinámica Molecular , Prolactina/metabolismo
12.
Artículo en Inglés | MEDLINE | ID: mdl-33478074

RESUMEN

Understanding the spatial pattern of soil chemical properties (SCPs) together with topological factors and soil management practices is essential for land management. This study examines the spatial changes in soil chemical properties and their impact on China's subtropical mountainous areas. In 2007 and 2017, 290 and 200 soil samples, respectively, were collected in Hefeng County, a mountainous county in central China. We used descriptive statistics and geostatistical methods, including ANOVA, semivariance, Moran's I, and fractal dimensions, to analyze the characteristics and spatial autocorrelation changes in soil organic matter (OM), available phosphorus (AP), available potassium (AK), and pH value from 2007 to 2017. We explored the relationship between each SCP and the relationship between SCPs with topographic parameters, soil texture, and cropping systems. The results show that the mean value of soil OM, AP, AK, and pH in Hefeng increased from 2007 to 2017. The spatial variation and spatial dependency of each SCP in 2007, excluding AP and AK in 2007, were higher than in 2017. The soil in areas with high topographic relief, profile curvature, and planform curvature had less AP, AK, and pH. Soil at higher elevation had lower OM (r = -0.197, p < 0.01; r = -0.334, p < 0.01) and AP (r = -0.043, p < 0.05; r = -0.121, p < 0.05) and higher AK (r = -0.305, p < 0.01; r =0.408, p < 0.01) in 2007 and 2017. Soil OM and AK in 2007 were significantly (p < 0.05) correlated with soil texture (p < 0.05). In contrast, oil AP and soil pH in 2007 and all SCPs in 2017 were poorly correlated with soil texture. The cropping systems played an important role in affecting all SCPs in 2007 (p < 0.01), while they only significantly affected AK in 2017 (p < 0.05). Our findings demonstrate that both topological factors, that is, the changes in cropping management and the changes in acid rain, impact soil chemical properties. The local government should place more focus on reducing soil acid amounts, soil AP content, and soil erosion by improving water conservancy facilities.


Asunto(s)
Nitrógeno , Suelo , China , Nitrógeno/análisis , Fósforo/análisis , Potasio/análisis
13.
Adv Sci (Weinh) ; 7(17): 1903341, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32995114

RESUMEN

Multifunctional nanoplatforms for imaging-guided synergistic antitumor treatment are highly desirable in biomedical applications. However, anticancer treatment is largely affected by the pre-existing hypoxic tumor microenvironment (TME), which not only causes the resistance of the tumors to photodynamic therapy (PDT), but also promotes tumorigenesis and tumor progression. Here, a continuous O2 self-enriched nanoplatform is constructed for multimodal imaging-guided synergistic phototherapy based on octahedral gold nanoshells (GNSs), which are constructed by a more facile and straightforward one-step method using platinum (Pt) nanozyme-decorated metal-organic frameworks (MOF) as the inner template. The Pt-decorated MOF@GNSs (PtMGs) are further functionalized with human serum albumin-chelated gadolinium (HSA-Gd, HGd) and loaded with indocyanine green (ICG) (ICG-PtMGs@HGd) to achieve a synergistic PDT/PTT effect and fluorescence (FL)/multispectral optoacoustic tomography (MSOT)/X-ray computed tomography (CT)/magnetic resonance (MR) imaging. The Pt-decorated nanoplatform endows remarkable catalase-like behavior and facilitates the continuous decomposition of the endogenous H2O2 into O2 to enhance the PDT effect under hypoxic TME. HSA modification enhances the biocompatibility and tumor-targeting ability of the nanocomposites. This TME-responsive and O2 self-supplement nanoparticle holds great potential as a multifunctional theranostic nanoplatform for the multimodal imaging-guided synergistic phototherapy of solid tumors.

14.
ACS Nano ; 14(2): 1533-1549, 2020 02 25.
Artículo en Inglés | MEDLINE | ID: mdl-32027482

RESUMEN

Although emerging evidence suggests that the pathogenesis of Parkinson's disease (PD) is closely related to the aggregation of alpha-synuclein (α-syn) in the midbrain, the clearance of α-syn remains an unmet clinical need. Here, we develop a simple and efficient strategy for fabricating the α-syn nanoscavenger for PD via a reprecipitation self-assembly procedure. The curcumin analogue-based nanoscavenger (NanoCA) is engineered to be capable of a controlled-release property to stimulate nuclear translocation of the major autophagy regulator, transcription factor EB (TFEB), triggering both autophagy and calcium-dependent exosome secretion for the clearance of α-syn. Pretreatment of NanoCA protects cell lines and primary neurons from MPP+-induced neurotoxicity. More importantly, a rapid arousal intranasal delivery system (RA-IDDS) was designed and applied for the brain-targeted delivery of NanoCA, which affords robust neuroprotection against behavioral deficits and promotes clearance of monomer, oligomer, and aggregates of α-syn in the midbrain of an MPTP mouse model of PD. Our findings provide a clinically translatable therapeutic strategy aimed at neuroprotection and disease modification in PD.


Asunto(s)
Curcumina/uso terapéutico , Nanoestructuras/química , Fármacos Neuroprotectores/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , alfa-Sinucleína/antagonistas & inhibidores , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Curcumina/síntesis química , Curcumina/química , Liberación de Fármacos , Neuroprotección/efectos de los fármacos , Fármacos Neuroprotectores/síntesis química , Fármacos Neuroprotectores/química , Células PC12 , Enfermedad de Parkinson/patología , Tamaño de la Partícula , Agregado de Proteínas/efectos de los fármacos , Ratas , Propiedades de Superficie , alfa-Sinucleína/metabolismo
15.
Methods Mol Biol ; 2054: 283-294, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31482462

RESUMEN

A series of ligand-targeted nanosystems have been rapidly exploited to selectively deliver drug molecules to desired cell populations. The conjugation of protein ligands to the nanoparticle (NP) surface endows nanovehicles with active targeting properties. However, the nonspecific covalent coupling of protein ligands to nanocarriers may compromise the protein targeting due to the uncontrolled ligand orientation as well as the decline in ligand activity during linkage process. With this regard, biomimetic synthetic strategies are employed for the preparation of genetically engineered nanovesicles (GNV) from cellular plasma membrane with targeting moieties on the surface in a ligand-oriented manner. Herein, we introduce the biomimetic synthetic strategy and procedures for GNV preparation. This chapter may guide readers to design analogous NPs for cell-specific targeting by displaying particular protein probes (e.g., antibody, nanobody, and single-chain antibody) on the surface of GNVs.


Asunto(s)
Antineoplásicos/administración & dosificación , Ingeniería Genética/métodos , Nanopartículas/química , Neoplasias/terapia , Nanomedicina Teranóstica/métodos , Animales , Antineoplásicos/farmacocinética , Materiales Biomiméticos/síntesis química , Línea Celular Tumoral , Membrana Celular/genética , Terapia Combinada/métodos , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacocinética , Composición de Medicamentos/métodos , Exosomas/genética , Humanos , Hipertermia Inducida/métodos , Liposomas , Ratones , Neoplasias/diagnóstico por imagen , Neoplasias/patología , Técnicas Fotoacústicas , Fotoquimioterapia/métodos , Anticuerpos de Cadena Única/administración & dosificación , Distribución Tisular , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Int J Biol Macromol ; 140: 782-793, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31401268

RESUMEN

Polysaccharide from Ganoderma lucidum is one of the best metal-ion chelating agents because of its structural characteristics and excellent functional activities. In this study, we synthesized and characterized a novel G. lucidum polysaccharide­chromium (III) [GLP-Cr(III)] complex. Response surface methodology (RSM) was used to optimize the reaction conditions for the maximum chelation rate of GLP-Cr(III) complex. The optimal reaction conditions obtained from RSM were as follows: concentration of CrCl3 5.71 mg/mL, pH 6.36, temperature 66.4 °C and time 2.0 h, respectively. The pH was the most significant factor, followed by reaction temperature and CrCl3 concentration. Under the optimal conditions, the experimental chelation rate was 94.17 ±â€¯1.0% for GLP-Cr(III) complex, which agreed closely with the predicted value (94.60%). Fourier transform infrared (FT-IR) spectroscopy revealed that the primary sites of chromium (III)-binding in G. lucidum polysaccharide were OH and CO groups, which induce the morphology change from flat sheet to rough surface. Meanwhile, according to the result of X-ray diffraction (XRD), the crystal degree of GLP was disappeared after chelation with Cr(III). The presence of a "blind zone" in the 1H NMR spectrum obviously indicated the binding of Cr(III) to GLP. Additionally, the effects of GLP-Cr(III) complex on hyperglycemia and hyperlipidemia in high fructose and fat diet-induced pre-diabetic mice were also investigated. Results showed that the serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting blood glucose levels and glucose tolerance in mice supplemented with GLP-Cr(III) complex (50 mg/kg day) were significantly lower than the model group (P < 0.01). More importantly, the GLP-Cr(III) complex had no significant adverse effects on the physiological metabolism, organ index, and liver tissue morphology of mice fed a normal diet. These results suggest that GLP-Cr(III) complex could be used as potential functional food ingredients for the prevention or treatment of hyperglycemia and hyperlipidemia.


Asunto(s)
Basidiomycota/química , Cromo/química , Polisacáridos Fúngicos/química , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Hipolipemiantes/química , Hipolipemiantes/farmacología , Animales , Glucemia , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/etiología , Dieta Alta en Grasa , Prueba de Tolerancia a la Glucosa , Masculino , Ratones , Análisis Espectral
17.
Nanoscale ; 10(13): 5864-5868, 2018 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-29560489

RESUMEN

In vivo assessment of vascular permeability and therapeutic response provides novel insights into photothermal therapy (PTT) that is currently under clinical investigation. We have developed noninvasive imaging strategies to improve the monitoring of nanoparticle-mediated PTT responses for personalized nanomedicine. Briefly, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and photoacoustic imaging (PAI) were applied to study the enhanced permeability and retention (EPR) effect in tumor models of different microvascular permeabilities (i.e., 4T1 mouse breast tumor model and HUH-7 human hepatoma model in nude mice). Magnetic resonance temperature imaging (MRTI) and diffusion-weighted MRI (DWI) showed that the 4T1 tumor model exhibits a higher PTT temperature response than that of the HUH-7 tumor model. Our findings demonstrate that the combined use of MRI and PAI techniques is useful in monitoring the vascular permeability and temperature status following PTT, promising to help guide PTT in future translational investigation.


Asunto(s)
Imagen por Resonancia Magnética , Neoplasias Experimentales/diagnóstico por imagen , Neoplasias Experimentales/terapia , Técnicas Fotoacústicas , Fototerapia , Animales , Línea Celular Tumoral , Humanos , Ratones , Ratones Desnudos
18.
Phytother Res ; 31(8): 1119-1127, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28504367

RESUMEN

The autophagy-lysosome pathway (ALP) is a primary means by which damaged organelles and long-lived proteins are removed from cells and their components recycled. Impairment of the ALP has been found to be linked to the pathogenesis of Parkinson's disease (PD), a chronic neurodegenerative disorder characterized by the accumulation of protein aggregates and loss of dopaminergic neurons in the midbrain. In recent years, some active compounds derived from plants have been found to regulate the ALP and to exert neuroprotective effects in experimental models of PD, raising the possibility that autophagy enhancement may be an effective therapeutic strategy in PD treatment. In this review, we summarize recent findings of natural products that enhance ALP and thereby protect against PD. Research articles were retrieved from PubMed using relevant keywords in combination. Papers related to the topic were identified, and then the reliability of the experiments was assessed in terms of methodology. The results suggest that targeting the ALP with natural products is a promising strategy for PD treatment. However, risk of bias exists in some studies due to the defective methodology. Rigorous experimental design following the guidelines of autophagy assays, molecular target identification and in vivo efficacy evaluation is critical for the development of ALP enhancers for PD treatment in future studies. Copyright © 2017 John Wiley & Sons, Ltd.


Asunto(s)
Autofagia/efectos de los fármacos , Productos Biológicos/farmacología , Lisosomas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Enfermedad de Parkinson/tratamiento farmacológico , Animales , Neuronas Dopaminérgicas/patología , Humanos
19.
Int J Mol Sci ; 18(2)2017 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-28134846

RESUMEN

Hippocampal neurogenesis plays a critical role in the formation of new neurons during learning and memory development. Attenuation of neurogenesis in the brain is one of the primary causes of dementia in Alzheimer's disease (AD), and, conversely, modulating the process of hippocampal neurogenesis benefit patients with AD. Traditional Chinese medicine (TCM), particularly herbal medicine, has been in use for thousands of years in Asia and many regions of the world for the treatment of cancer, cardiovascular diseases and neurodegenerative diseases. In this review, we summarize the role of neurotrophic factors, signal transducing factors, epigenetic modulators and neurotransmitters in neurogenesis, and we also discuss the functions of several Chinese herbs and their active molecules in activating multiple pathways involved in neurogenesis. TCM herbs target pathways such as Notch, Wnt, Sonic Hedgehog and receptor tyrosine kinase pathway, leading to activation of a signaling cascade that ultimately enhances the transcription of several important genes necessary for neurogenesis. Given these pathway activating effects, the use of TCM herbs could be an effective therapeutic strategy for the treatment of AD.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Neurogénesis , Animales , Humanos , Medicina Tradicional China , Transducción de Señal
20.
Chin Med ; 11: 6, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26913057

RESUMEN

Diabetic nephropathy (DN) is a severe micro vascular complication accompanying diabetes mellitus that affects millions of people worldwide. End-stage renal disease occurs in nearly half of all DN patients, resulting in large medical costs and lost productivity. The course of DN progression is complicated, and effective and safe therapeutic strategies are desired. While the complex nature of DN renders medicines with a single therapeutic target less efficacious, Chinese medicine, with its holistic view targeting the whole system of the patient, has exhibited efficacy for DN management. This review aims to describe the experimental evidence for Chinese medicines in DN management, with an emphasis on the underlying mechanisms, and to discuss the combined use of herbs and drugs in DN treatment.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA