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1.
Proc Natl Acad Sci U S A ; 121(3): e2314557121, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38190534

RESUMEN

CA2 pyramidal neurons (PNs) are associated with social behaviors. The mechanisms, however, remain to be fully investigated. Here, we report that Efr3b, a protein essential for phospholipid metabolism at the plasma membrane, is widely expressed in the brain, especially in the hippocampal CA2/CA3 areas. To assess the functional significance of Efr3b in the brain, we generated Efr3bf/f mice and crossed them with Nestin-cre mice to delete Efr3b specifically in the brain. We find that Efr3b deficiency in the brain leads to deficits of social novelty recognition and hypoexcitability of CA2 PNs. We then knocked down the expression of Efr3b specifically in CA2 PNs of C57BL/6J mice, and our results showed that reducing Efr3b in CA2 PNs also resulted in deficits of social novelty recognition and hypoexcitability of CA2 PNs. More interestingly, restoring the expression of Efr3b in CA2 PNs enhances their excitability and improves social novelty recognition in Efr3b-deficient mice. Furthermore, direct activation of CA2 PNs with chemogenetics improves social behaviors in Efr3b-deficient mice. Together, our data suggest that Efr3b is essential for social novelty by modulating the excitability of CA2 PNs.


Asunto(s)
Encéfalo , Reconocimiento en Psicología , Animales , Ratones , Ratones Endogámicos C57BL , Membrana Celular , Células Piramidales
2.
Pharmacol Res ; 203: 107185, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38615875

RESUMEN

Microbes, including bacteria, viruses, fungi, and other eukaryotic organisms, are commonly present in multiple organs of the human body and contribute significantly to both physiological and pathological processes. Nowadays, the development of sequencing technology has revealed the presence and composition of the intratumoral microbiota, which includes Fusobacterium, Bifidobacteria, and Bacteroides, and has shed light on the significant involvement in the progression of colorectal cancer (CRC). Here, we summarized the current understanding of the intratumoral microbiota in CRC and outline the potential translational and clinical applications in the diagnosis, prevention, and treatment of CRC. We focused on reviewing the development of microbial therapies targeting the intratumoral microbiota to improve the efficacy and safety of chemotherapy and immunotherapy for CRC and to identify biomarkers for the diagnosis and prognosis of CRC. Finally, we emphasized the obstacles and potential solutions to translating the knowledge of the intratumoral microbiota into clinical practice.


Asunto(s)
Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/tratamiento farmacológico , Animales , Microbioma Gastrointestinal , Microbiota , Inmunoterapia/métodos
3.
Epilepsy Behav ; 157: 109887, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38905916

RESUMEN

AIM: To explore multiple features of attention impairments in patients with temporal lobe epilepsy (TLE). METHODS: A total of 93 patients diagnosed with TLE at Xiangya Hospital during May 2022 and December 2022 and 85 healthy controls were included in this study. Participants were asked to complete neuropsychological scales and attention network test (ANT) with recording of eye-tracking and electroencephalogram. RESULTS: All means of evaluation showed impaired attention functions in TLE patients. ANT results showed impaired orienting (p < 0.001) and executive control (p = 0.041) networks. Longer mean first saccade time (p = 0.046) and more total saccadic counts (p = 0.035) were found in eye-tracking results, indicating abnormal alerting and orienting networks. Both alerting, orienting and executive control networks were abnormal, manifesting as decreased amplitudes (N1 & P3, p < 0.001) and extended latency (P3, p = 0.002). The energy of theta, alpha and beta were all sensitive to the changes of alerting and executive control network with time, but only beta power was sensitive to the changes of orienting network. CONCLUSION: Our findings are helpful for early identification of patients with TLE combined with attention impairments, which have strong clinical guiding significance for long-term monitoring and intervention.

4.
Molecules ; 28(14)2023 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-37513483

RESUMEN

Tumor immunotherapy, compared with other treatment strategies, has the notable advantage of a long-term therapeutic effect for preventing metastasis and the recurrence of tumors, thus holding great potential for the future of advanced tumor therapy. However, due to the poor water solubility of immune modulators and immune escape properties of tumor cells, the treatment efficiency of immunotherapy is usually significantly reduced. Cyclodextrin (CD) has been repeatedly highlighted to be probably one of the most investigated building units for cancer therapy due to its elegant integration of an internal hydrophobic hollow cavity and an external hydrophilic outer surface. The application of CD for immunotherapy provides new opportunities for overcoming the aforementioned obstacles. However, there are few published reviews, to our knowledge, summarizing the use of CD for cancer immunotherapy. For this purpose, this paper provides a comprehensive summary on the application of CD for immunotherapy with an emphasis on the role, function, and reported strategies of CD in mediating immunotherapy. This review summarizes the research progress made in using CD for tumor immunotherapy, which will facilitate the generation of various CD-based immunotherapeutic delivery systems with superior anticancer efficacy.


Asunto(s)
Ciclodextrinas , Neoplasias , Humanos , Ciclodextrinas/uso terapéutico , Ciclodextrinas/química , Neoplasias/tratamiento farmacológico , Inmunoterapia , Factores Inmunológicos/uso terapéutico
5.
Environ Sci Technol ; 56(9): 5753-5762, 2022 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-35420409

RESUMEN

We report an electrolysis system using NiFe layered double hydroxide/CoMoO4/nickel foam (NFLDH/CMO/NF) as the anode and CMO/NF as the cathode for simultaneous phenol electro-oxidation and water electrolysis. This system shows high performance for both phenol degradation and hydrogen evolution. We demonstrate that the degradation rate of phenol on the active anode is governed by the mass transfer rate at a low phenol concentration (0.5-2 mM) and by the electro-oxidation rate at a high phenol concentration (5 mM). The anodic oxygen evolution reaction (OER) can promote the phenol degradation through enhanced mass transfer efficiency. More importantly, the common deactivation issue of phenol electro-oxidation on the inert anode can be eliminated by the high OER activity of the active anode. The constructed full electrolytic cell only needs a low potential of 1.498 V to achieve 10 mA/cm2 for water electrolysis. The reported promotion effect of phenol degradation by OER as well as the improved anode resistance to deactivation offer new insights into efficient and robust waste-to-resource electrolysis system for water treatment.


Asunto(s)
Fenol , Contaminantes Químicos del Agua , Electrodos , Hidrógeno , Oxígeno , Fenoles , Titanio , Aguas Residuales
6.
Environ Sci Technol ; 56(4): 2665-2676, 2022 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-35077141

RESUMEN

Selective removal of organic pollutants by advanced oxidation methods has been receiving increasing attention for environmental remediation. In this study, a novel catalyst, which can selectively oxidize phenolic compounds (PCs) based on their hydrophobicity, composed of metal-organic-framework-derived Fe/Fe3O4 and three-dimensional reduced graphene oxide (rGOF) is designed for peroxydisulfate (PDS) activation. This heterogeneous PDS activation system can completely degrade hydrophobic PCs within 30 min. By investigating the hydrophobic properties of eight representative PCs, a positive correlation between the hydrophobicity of PC and the reaction kinetics is reported for the first time. The selective removal stems from the strong interaction between highly hydrophobic PCs and the catalyst. Moreover, the mechanism investigation shows that the degradation reaction is triggered by interface reactive oxygen species (ROS). Our study reveals that the selective degradation of organic pollutants by PDS activation depends on the hydrophilic and hydrophobic properties of the pollutant and catalyst. The reported results provide new insights into a highly selective and efficient PDS activation system for organic pollutant removal.


Asunto(s)
Contaminantes Ambientales , Contaminantes Químicos del Agua , Catálisis , Interacciones Hidrofóbicas e Hidrofílicas , Oxidación-Reducción , Fenoles , Especies Reactivas de Oxígeno , Contaminantes Químicos del Agua/análisis
7.
Molecules ; 27(4)2022 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-35209018

RESUMEN

The solubility of dehydroabietic acid in (-)-α-pinene, p-cymene, (-)-ß-caryophyllene, (-)-α-pinene + p-cymene, (-)-ß-caryophyllene + p-cymene and (-)-α-pinene + (-)-ß-caryophyllene were determined using the laser monitoring method at atmospheric pressure. The solubility of dehydroabietic acid was positively correlated with temperature from 295.15 to 339.46 K. (-)-α-pinene, p-cymene, and (-)-ß-caryophyllene were found to be suitable for the solubilization of dehydroabietic acid. In addition, the non-random two liquid (NRTL), universal quasi-chemical (UNIQUAC), modified Apelblat, modified Wilson, modified Wilson-van't Hoff, and λh models were applied to correlate the determined solubility data. The modified Apelblat model gave the minor deviation for dehydroabietic acid in monosolvents, while the λh equation showed the best result in the binary solvents. A comparative analysis of compatibility between solutes and solvents was carried out using Hansen solubility parameters. The thermodynamic functions of ΔsolH0, ΔsolS0, ΔsolG0 were calculated according to the van't Hoff equation, indicating that the dissolution was an entropy-driven heat absorption process. The Conductor-like Screening Model for Real Solvents (COSMO-RS) combined with an experimental value was applied to predict the reasonable solubility data of dehydroabietic acid in the selected solvents systems. The interaction energy of the dehydroabietic acid with the solvent was analyzed by COSMO-RS.

8.
Anal Chem ; 93(22): 8010-8018, 2021 06 08.
Artículo en Inglés | MEDLINE | ID: mdl-34019758

RESUMEN

Silver (Ag) is a widely used heavy metal, and its oxidation state (Ag+) causes serious harm to organisms after bioaccumulation and biomagnification, posing urgent demand for the rapid, efficient, and simply operated Ag+ detection techniques. In this work, a fast, portable, and label-free Ag+ detection sensor based on a Ti3C2Tx MXene field-effect transistor (FET) is reported. The Ti3C2Tx MXene works as the sensing element in the FET sensor, which shows excellent sensing performance, i.e., fast response (few seconds) and good sensitivity and selectivity to Ag+ without any detection label or probe. Utilizing the visual photograph, transmission electron microscopy image, and Ag elemental mapping analysis, the sensing mechanism of the label-free Ti3C2Tx MXene FET sensor is demonstrated to be the in situ reduction of Ag+ and the formation of Ag nanoparticles (AgNPs). Moreover, Ag+ detection in real samples shows that the proposed FET devices have satisfactory sensing capability for Ag+ in tap water and river water. This study puts forward a novel FET strategy for Ag+ detection in aqueous systems, which is of essential and inspiring meaning for motivating the potential applications of MXene-based sensor devices in analytical applications and the realization of on-site environmental monitoring.


Asunto(s)
Nanopartículas del Metal , Plata , Titanio , Agua
9.
Respir Res ; 21(1): 201, 2020 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-32727465

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a new respiratory and systemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The purpose of the present study was to investigate the association between cytokine profiles and lung injury in COVID-19 pneumonia. METHODS: This retrospective study was conducted in COVID-19 patients. Demographic characteristics, symptoms, signs, underlying diseases, and laboratory data were collected. The patients were divided into COVID-19 with pneumonia and without pneumonia. CT severity score and PaO2/FiO2 ratio were used to assess lung injury. RESULTS: 106 patients with 12 COVID-19 without pneumonia and 94 COVID-19 with pneumonia were included. Compared with COVID-19 without pneumonia, COVID-19 with pneumonia had significantly higher serum interleukin (IL)-2R, IL-6, and tumor necrosis factor (TNF)-α. Correlation analysis showed that CT severity score and PaO2/FiO2 were significantly correlated with age, presence of any coexisting disorder, lymphocyte count, procalcitonin, IL-2R, and IL-6. In multivariate analysis, log IL6 was the only independent explanatory variables for CT severity score (ß = 0.397, p < 0.001) and PaO2/FiO2 (ß = - 0.434, p = 0.003). CONCLUSIONS: Elevation of circulating cytokines was significantly associated with presence of pneumonia in COVID-19 and the severity of lung injury in COVID-19 pneumonia. Circulating IL-6 independently predicted the severity of lung injury in COVID-19 pneumonia.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/complicaciones , Citocinas/sangre , Lesión Pulmonar/etiología , Neumonía Viral/complicaciones , Adulto , Biomarcadores/sangre , COVID-19 , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/epidemiología , Femenino , Humanos , Lesión Pulmonar/sangre , Lesión Pulmonar/diagnóstico , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/sangre , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Estudios Retrospectivos , SARS-CoV-2 , Tomografía Computarizada por Rayos X
10.
Molecules ; 25(2)2020 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-31940875

RESUMEN

The xylitol ester of hydrogenated rosin (XEHR) was obtained for the first time from biomass-based hydrogenated rosin and xylitol using an environmentally friendly, high-pressure CO2 catalytic synthesis. This compound is intended for use as an emulsifier for food. Analyses by ICP-AES showed the absence of heavy metal residues in the product, such that it met food standards. Fourier transform infrared and nuclear magnetic resonance spectroscopies together with gel permeation chromatography confirmed the successful esterification and the formation of a monoester and diester with molar masses of 427 and 772 g/mol. The emulsification of water/soybean oil mixtures by adding the XEHR was assessed at pH values of 4, 6.86, and 10 and in the presence of NaCl, KCl, MgCl2, and CaCl2. The XEHR was found to act as an emulsifier by reducing the interfacial tension of such mixtures to less than 2 mN/m under all conditions. The highest emulsifying activity index (9.52 m2/g) and emulsifying stability index (94.53%) were obtained after adding MgCl2 (100 mM). Particle size and confocal microscopy showed that the presence of salts gave a more uniform droplet size and a finer emulsion structure. The high viscosities of the emulsions containing salts also suggested a more cohesive oil droplet network.


Asunto(s)
Emulsionantes/síntesis química , Ésteres/química , Aditivos Alimentarios/síntesis química , Resinas de Plantas/química , Xilitol/química , Biomasa , Dióxido de Carbono/química , Emulsionantes/análisis , Ésteres/análisis , Aditivos Alimentarios/análisis , Humanos , Concentración de Iones de Hidrógeno , Hidrogenación , Cloruro de Magnesio/química , Tamaño de la Partícula , Presión , Aceite de Soja/química , Tensión Superficial , Agua/química , Xilitol/análisis
11.
Cell Physiol Biochem ; 49(3): 1064-1073, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30196278

RESUMEN

BACKGROUND/AIMS: The roots of Averrhoa carambola L. (Oxalidaceae) have long been used as a traditional Chinese medicine for the treatment of headaches, vomiting, coughing and hangovers. 2-dodecyl-6-methoxycyclohexa-2, 5-1, 4-dione (DMDD) has been isolated from A. carambola L. roots, and this study was carried out to investigate the potential beneficial effects of DMDD on neuron apoptosis and memory deficits in Alzheimer's disease. METHODS: The effects of a DMDD on learning and memory in APP/PS1 transgenic AD mice in vivo were investigated via Morris water maze and Y-type electric maze tests. In vitro, Cell viability was assessed by CCK-8. Apoptosis was assessed by Annexin V-FITC/PI flow cytometry assay, and transmission electron microscopy assay. Relative quantitative real-time PCR and Western blot were used to determine the expressions of genes and proteins. RESULTS: The spatial learning and memory deficit, fear memory deficit, as well as apoptosis and loss of neuron in hippocampal area of APP/PS1 mice were reversed by DMDD in APP/PS1 transgenic AD mice. DMDD protected against the Aß1-42-induced apoptosis, loss of mitochondria membrane potential, induction of pro-apoptotic Bcl-2 family protein Bax, reduction of anti-apoptotic Bcl-2 family proteins Bcl-2, and activation of Caspase-3, and -9 in PC-12 cells. The Bcl-2/Bax ratio was also increased in DMDD-pretreated PC-12 cells in vitro and APP/PS1 mice in vivo. CONCLUSION: DMDD has potential benefit on treating learning and memory deficit in APP/PS1 transgenic AD mice, and its effects may be associated with reversing the apoptosis of neuron via inhibiting Bax/Bcl-2 mediated mitochondrial membrane potential loss.


Asunto(s)
Enfermedad de Alzheimer/patología , Apoptosis/efectos de los fármacos , Averrhoa/química , Neuronas/metabolismo , Sustancias Protectoras/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/toxicidad , Precursor de Proteína beta-Amiloide/genética , Animales , Averrhoa/metabolismo , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Modelos Animales de Enfermedad , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Ratones , Ratones Transgénicos , Neuronas/efectos de los fármacos , Neuronas/patología , Células PC12 , Fragmentos de Péptidos/toxicidad , Raíces de Plantas/química , Raíces de Plantas/metabolismo , Sustancias Protectoras/química , Sustancias Protectoras/uso terapéutico , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo
12.
J Cell Mol Med ; 20(6): 1062-75, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26769343

RESUMEN

After spinal cord injury (SCI), disruption of blood-spinal cord barrier (BSCB) elicits blood cell infiltration such as neutrophils and macrophages, contributing to permanent neurological disability. Previous studies show that epidermal growth factor (EGF) produces potent neuroprotective effects in SCI models. However, little is known that whether EGF contributes to the integrity of BSCB. The present study is performed to explore the mechanism of BSCB permeability changes which are induced by EGF treatment after SCI in rats. In this study, we demonstrate that EGF administration inhibits the disruption of BSCB permeability and improves the locomotor activity in SCI model rats. Inhibition of the PI3K/Akt pathways by a specific inhibitor, LY294002, suppresses EGF-induced Rac1 activation as well as tight junction (TJ) and adherens junction (AJ) expression. Furthermore, the protective effect of EGF on BSCB is related to the activation of Rac1 both in vivo and in vitro. Blockade of Rac1 activation with Rac1 siRNA downregulates EGF-induced TJ and AJ proteins expression in endothelial cells. Taken together, our results indicate that EGF treatment preserves BSCB integrity and improves functional recovery after SCI via PI3K-Akt-Rac1 signalling pathway.


Asunto(s)
Factor de Crecimiento Epidérmico/farmacología , Factor de Crecimiento Epidérmico/uso terapéutico , Transducción de Señal , Traumatismos de la Médula Espinal/sangre , Traumatismos de la Médula Espinal/tratamiento farmacológico , Médula Espinal/patología , Uniones Adherentes/efectos de los fármacos , Uniones Adherentes/metabolismo , Animales , Cromonas/farmacología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Factor de Crecimiento Epidérmico/administración & dosificación , Femenino , Glucosa/deficiencia , Humanos , Morfolinas/farmacología , Fármacos Neuroprotectores/farmacología , Oxígeno , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Proteolisis/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-Dawley , Recuperación de la Función/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/metabolismo , Proteína de Unión al GTP rac1/metabolismo
13.
Cell Physiol Biochem ; 39(3): 1040-50, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27537353

RESUMEN

BACKGROUND: The previous studies have demonstrated that the polysaccharide isolated from Tarphochlamys affinis (PTA) exhibits anti-tumor effect on S180 tumor-bearing mice and protective effects against hepatic injury. METHODS: In this study, we investigated the anti-tumor activity and possible underlying mechanism of PTA on liver cancer using a murine H22 hepatocarcinoma model. RESULTS: PTA was capable of repressing transplanted H22 solid hepatic tumor cell growth in vivo. The relative weight of immune organs (spleen and thymus) and lymphocyte proliferation induced by ConA or LPS were improved after PTA treatment. Furthermore, treatment with PTA promoted immune-stimulating serum cytokine secretion in H22 tumor-bearing mice. Additionally, the percentage of CD4+ T lymphocytes, CD8+ T lymphocytes and NK cells was increased in tumor-bearing mice following PTA administration. In tumor tissue, PTA significantly up-regulated the expression of Bax and p53 proteins and down-regulated the expression of Bcl-2 protein. In addition, at the therapeutic dose, PTA displayed very few toxic effects to major organs, such as the liver and kidney, in tumor-bearing mice. CONCLUSION: In H22 tumor-bearing mice, PTA exhibited prominent anti-tumor activity in vivo. The possible mechanism of action might be related to enhanced host immune system function and induction of H22 tumor cell apoptosis.


Asunto(s)
Acanthaceae/química , Antineoplásicos Fitogénicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Polisacáridos/farmacología , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Concanavalina A/farmacología , Femenino , Inyecciones Subcutáneas , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/patología , Lipopolisacáridos/farmacología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas Experimentales/genética , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/patología , Ratones , Polisacáridos/aislamiento & purificación , Cultivo Primario de Células , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/inmunología , Transducción de Señal , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/patología , Timo/efectos de los fármacos , Timo/inmunología , Timo/patología , Proteína p53 Supresora de Tumor/agonistas , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/inmunología , Proteína X Asociada a bcl-2/agonistas , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/inmunología
14.
Cell Physiol Biochem ; 40(5): 993-1004, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27941348

RESUMEN

BACKGROUND/AIMS: The roots of Averrhoa carambola L. (Oxalidaceae) have long been used as a traditional Chinese medicine for the treatment of diabetes and diabetes-related diseases. 2-dodecyl-6-methoxycycyclohexa-2,5-1,4-dione (DMDD) has been isolated from A. carambola L. roots, and this study was carried out to investigate the potential beneficial effects of DMDD on obesity and insulin resistance induced by a high-fat diet (HFD) in mice. METHODS: C57BL/6J mice were fed a HFD for 16 weeks and orally administered DMDD (12.5, 25, or 50 mg/kg of body weight per day) and metformin (280 mg/kg of body weight per day) for the last 4 weeks. RESULTS: The body weights and adipose tissue weights as well as the serum levels of blood glucose, total cholesterol, triglycerides, free fatty acids, insulin, interleukin-6, and tumor necrosis factor-α were significantly decreased by DMDD, and the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor (Myd88) in the epididymal adipose tissue was downregulated by DMDD. In contrast, insulin sensitivity was enhanced. The results of the glucose tolerance tests, insulin tolerance tests, and insulin release tests indicated that there was a marked improvement in insulin secretion, and the areas under the curve corresponding to the three tests were also significantly decreased by DMDD. The activities of superoxide dismutase and glutathione peroxidase were simultaneously enhanced, whereas the content of malondialdehyde was decreased by DMDD in the liver homogenates of the C57BL/6J mice. In addition, hepatic steatosis and adipocyte hypertrophy, as assessed by H&E staining of liver and adipose tissues, were significantly improved by DMDD. CONCLUSION: These data suggest that MDD has potential benefits for the treatment of HFD-induced obesity and insulin resistance, and its effects may be associated with improvements in lipid metabolism and inhibition of the expression of TLR4 in adipose tissues.


Asunto(s)
Averrhoa/química , Ciclohexenos/uso terapéutico , Dieta Alta en Grasa/efectos adversos , Resistencia a la Insulina , Obesidad/tratamiento farmacológico , Raíces de Plantas/química , Sustancias Protectoras/uso terapéutico , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Antioxidantes/metabolismo , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Ciclohexenos/química , Ciclohexenos/farmacología , Citocinas/sangre , Ayuno , Hígado Graso/sangre , Hígado Graso/tratamiento farmacológico , Hígado Graso/patología , Conducta Alimentaria/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Prueba de Tolerancia a la Glucosa , Insulina/sangre , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Ratones Endogámicos C57BL , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Obesidad/sangre , Obesidad/genética , Tamaño de los Órganos/efectos de los fármacos , Fitoterapia , Sustancias Protectoras/química , Sustancias Protectoras/farmacología , Receptor Toll-Like 4/metabolismo
15.
Cell Physiol Biochem ; 39(5): 1705-1715, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27643515

RESUMEN

BACKGROUND/AIMS: Studies have demonstrated that 2-dodecyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione (DMDD), isolated from the roots of Averrhoa carambola L., has significant therapeutic potential for the treatment of diabetes. However, the protective effect of DMDD against pancreatic beta cell dysfunction has never been reported. We investigated whether DMDD protected against palmitic acid-induced dysfunction in pancreatic ß-cell line Min6 cells by attenuating the inflammatory response and apoptosis and to shed light on its possible mechanism. METHODS: Cell viability was assessed by CCK-8. Glucose-stimulated insulin secretion levels and inflammatory cytokines levels were examined by ELISA. Apoptosis was assessed by Annexin V-FITC/PI Flow cytometry assay, Hoechst 33342/PI double-staining assay, and Transmission electron microscopy assay. Relative quantitative real-time PCR and western blot were used to determine the expressions of genes and proteins. RESULTS: Cell viability and glucose-stimulated insulin secretion levels were increased in DMDD-pretreated Min6 cells. DMDD inhibited inflammatory cytokines IL-6, TNF-α and MCP-1 generations in palmitic acid (PA)-induced Min6 cells. Moreover, DMDD protected against PA-induced Min6 cells apoptosis and the expression of Cleaved-Caspase-3, -8 and -9 were down-regulated and the Bcl-2/Bax ratio was increased in DMDD-pretreated Min6 cells. In addition, the expression of TLR4, MyD88 and NF-κB were down-regulated in DMDD-pretreated Min6 cells and TAK-242-pretreated group cells. CONCLUSIONS: DMDD protected Min6 cells against PA-induced dysfunction by attenuating the inflammatory response and apoptosis, and its mechanism of this protection was associated with inhibiting the TLR4-MyD88-NF-κB signaling pathway.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Averrhoa/química , Ciclohexenos/farmacología , Células Secretoras de Insulina/efectos de los fármacos , Ácido Palmítico/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Caspasas/genética , Caspasas/metabolismo , Línea Celular Transformada , Supervivencia Celular/efectos de los fármacos , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Ciclohexenos/aislamiento & purificación , Regulación de la Expresión Génica , Inflamación , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , Interleucina-6/genética , Interleucina-6/metabolismo , Ratones , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Ácido Palmítico/farmacología , Raíces de Plantas/química , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Transducción de Señal/genética , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo
16.
Tumour Biol ; 37(11): 14961-14967, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27651160

RESUMEN

Homeobox C8 (HOXC8) has been implicated in cell growth, migration, and metastasis of various cancers, yet its role in osteosarcoma remains to be explored. In the present study, resected osteosarcoma specimens from 50 patients were enrolled to evaluate the expression of HOXC8 protein by immunohistochemistry (IHC). In vitro and in vivo assays were used to determine the effect of HOXC8 on cell growth, migration, and tumor growth. HOXC8 expression was observed in 31 (62.0 %) of the 50 primary tumors and significantly associated with poorly or un-differentiated specimens (P = 0.031) and larger tumor size (P = 0.049). Survival analysis demonstrated that HOXC8 is a candidate predictive factor in predicting patients' outcome and chemotherapeutic effect. HOXC8 knockdown led to inhibition of tumor cell proliferation and migration in vitro by inhibiting MMP-9 expression and tumor growth in vivo. Our results strongly suggest that HOXC8 is involved in the tumorigenesis of osteosarcoma and might serve as a novel predictor for patients' outcome.


Asunto(s)
Neoplasias Óseas/patología , Movimiento Celular/genética , Proliferación Celular/genética , Proteínas de Homeodominio/genética , Metaloproteinasa 9 de la Matriz/biosíntesis , Osteosarcoma/patología , Adolescente , Animales , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Proteínas de Homeodominio/metabolismo , Humanos , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Interferencia de ARN , ARN Interferente Pequeño , Trasplante Heterólogo , Resultado del Tratamiento
17.
Clin Exp Hypertens ; 38(7): 571-577, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27650941

RESUMEN

The aim of our study is to explore the involvement of PPARα and PPARγ in Ang II-induced endothelial injury. We found that Ang II significantly elevated the oxidative stress in HUVECs, causing apoptosis and cellular impairment in a time-dependent pattern. Activation of either PPARα by docosahexaenoic acid (DHA) or PPARγ by rosiglitazone protected the endothelial cells. Interestingly, a more significant effect was observed when DHA and rosiglitazone were administrated together. Moreover, we found that this protection was mediated through the PI3K/Akt pathway. Our study may help to understand the mechanism of endothelial dysfunction, contributing to the treatment of hypertension and other endothelial-related diseases.


Asunto(s)
Angiotensina II/metabolismo , Ácidos Docosahexaenoicos/farmacología , Células Endoteliales , Estrés Oxidativo/efectos de los fármacos , PPAR alfa/metabolismo , PPAR gamma/metabolismo , Tiazolidinedionas/farmacología , Apoptosis/efectos de los fármacos , Células Cultivadas , Citoprotección/fisiología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/fisiología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Hipertensión , Fosfatidilinositol 3-Quinasas/metabolismo , Sustancias Protectoras/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Rosiglitazona , Transducción de Señal/efectos de los fármacos
18.
Int J Mol Sci ; 17(1)2015 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-26729092

RESUMEN

Astrocytes have critical roles in immune defense, homeostasis, metabolism, and synaptic remodeling and function in the central nervous system (CNS); however, excessive activation of astrocytes with increased intermediate filaments following neuronal trauma, infection, ischemia, stroke, and neurodegenerative diseases results in a pro-inflammatory environment and promotes neuronal death. As an important neurotrophic factor, the secretion of endogenous basic fibroblast growth factor (bFGF) contributes to the protective effect of neuronal cells, but the mechanism of bFGF in reactive astrogliosis is still unclear. In this study, we demonstrated that exogenous bFGF attenuated astrocyte activation by reducing the expression of glial fibrillary acidic protein (GFAP) and other markers, including neurocan and vimentin, but not nestin and decreased the levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), via the regulation of the upstream toll-like receptor 4/nuclear factor κB (TLR4/NFκB) signaling pathway. Our study suggests that the function of bFGF is not only related to the neuroprotective and neurotrophic effect but also involved in the inhibition of excessive astrogliosis and glial scarring after neuronal injury.


Asunto(s)
Astrocitos/patología , Factor 2 de Crecimiento de Fibroblastos/fisiología , Gliosis/fisiopatología , FN-kappa B , Transducción de Señal , Receptor Toll-Like 4 , Animales , Astrocitos/metabolismo , Astrocitos/fisiología , Células Cultivadas , Citocinas/genética , Regulación hacia Abajo , Proteína Ácida Fibrilar de la Glía/genética , Gliosis/metabolismo , Neurocano/genética , Ratas , Vimentina/genética
19.
J Int Med Res ; 52(3): 3000605241233157, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38546265

RESUMEN

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) constitutes a group of autoimmune neuroinflammatory conditions that are characterized by positive serum MOG-immunoglobulin G antibodies. The relationship between MOGAD and immune factors remains unclear. Herein, we report a man in his early 30s who initially presented symptoms of headache and low-grade fever persisting for 20 days. The patient experienced isolated meningitis onset and had recurrent meningitis as the primary clinical feature, which manifested as low-grade fever, headache, and neck rigidity. Although cranial magnetic resonance imaging showed no abnormalities, immunotherapy was promptly administered upon diagnosing MOGAD through positive MOG-specific antibody testing of cerebrospinal and serum fluids. Notably, the patient's symptoms exhibited rapid improvement following treatment. Although meningitis is traditionally associated with infectious diseases, it can also occur in antibody-related autoimmune diseases that affect the central nervous system. Consequently, MOGAD should be considered in cases of aseptic meningitis with an unknown etiology, to facilitate definitive diagnosis and enhance patient prognosis.


Asunto(s)
Enfermedades Autoinmunes , Meningitis , Humanos , Masculino , Autoanticuerpos , Cefalea , Meningitis/diagnóstico , Glicoproteína Mielina-Oligodendrócito , Adulto
20.
Food Chem ; 458: 140287, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38991240

RESUMEN

Procyanidin B2 (Pac B2) has attracted much attention due to its strong antioxidant activity, but poor in vivo stability limits its wide application in food and medicine. In this paper, composite nanoparticles (NPs) were constructed using abietic acid (AA) as a carrier, which significantly enhanced Pac B2 stability. A spherical morphology and average diameter of 396.05 nm were observed in AA-Pac B2 NPs synthesized by solvent co-precipitation. Pac B2 encapsulation was 11.28 %, and thermal stability is improved. Infrared, Ultraviolet spectrum, and MD (molecular dynamics) spectroscopy revealed hydrogen bonding and hydrophobic interaction between AA and Pac B2. For up to 2 h at 37 °C, Pac B2 can be sustainably released in simulated gastric and intestinal fluids. In vitro, AA-Pac B2 NPs at the same concentration exhibited higher bioavailability and uptake efficiency than free Pac B2. The data demonstrate the potential of AA NPs for improving polyphenol thermal stability and bioavailability.

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