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1.
Medicine (Baltimore) ; 102(32): e34728, 2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37565866

RESUMEN

BACKGROUND: Rheumatoid arthritis (RA) is a type of difficult-to-cure arthralgia with a worldwide prevalence. It severely affects people's living standards. For a long time, bee venom has been used to treat RA and has shown good results. Melittin is the main active component of bee venom used for RA treatment, but the molecular mechanism of melittin in RA treatments remains unclear. METHODS: Potential melittin and RA targets were obtained from relevant databases, and common targets of melittin and RA were screened. The STRING database was used to build the PPI network and screen the core targets after visualization. The core targets were enriched by Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway. Finally, the binding of melittin to target proteins was evaluated through simulated molecular docking, which verified the reliability of the prediction results of network pharmacology. RESULTS: In total, 138 melittin targets and 5795 RA targets were obtained from relevant databases, and 90 common targets were obtained through intersection. Eighteen core targets, such as STAT3, AKT1, tumor necrosis factor, and JUN, were screened out. Enrichment analysis results suggested that melittin plays an anti-RA role mainly through tumor necrosis factor, interleukin-17, toll-like receptors, and advanced glycation end products-RAGE signaling pathways, and pathogenic bacterial infection. Molecular docking results suggested that melittin has good docking activity with core target proteins. CONCLUSION: RA treatment with melittin is the result of a multi-target and multi-pathway interaction. This study offers a theoretical basis and scientific evidence for further exploring melittin in RA therapy.


Asunto(s)
Artritis Reumatoide , Venenos de Abeja , Medicamentos Herbarios Chinos , Humanos , Meliteno/farmacología , Meliteno/uso terapéutico , Simulación del Acoplamiento Molecular , Farmacología en Red , Reproducibilidad de los Resultados , Factor de Necrosis Tumoral alfa , Artritis Reumatoide/tratamiento farmacológico , Medicina Tradicional China
2.
Medicine (Baltimore) ; 102(22): e33542, 2023 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-37266651

RESUMEN

Fracture is a global public health disease. Bone health and fracture risk have become the focus of public and scientific attention. Observational studies have reported that tea consumption is associated with fracture risk, but the results are inconsistent. The present study used 2-sample Mendelian randomization (MR) analysis. The inverse variance weighted method, employing genetic data from UK Biobank (447,485 cases) of tea intake and UK Biobank (Genome-wide association study Round 2) project (361,194 cases) of fractures, was performed to estimate the causal relationship between tea intake and multiple types of fractures. The inverse variance weighted indicated no causal effects of tea consumption on fractures of the skull and face, shoulder and upper arm, hand and wrist, femur, calf, and ankle (odds ratio = 1.000, 1.000, 1.002, 0.997, 0.998; P = .881, 0.857, 0.339, 0.054, 0.569, respectively). Consistent results were also found in MR-Egger, weighted median, and weighted mode. Our research provided evidence that tea consumption is unlikely to affect the incidence of fractures.


Asunto(s)
Fracturas Óseas , Estudio de Asociación del Genoma Completo , Humanos , Análisis de la Aleatorización Mendeliana , Extremidad Superior , Muñeca , Fracturas Óseas/etiología , Fracturas Óseas/genética , Té/efectos adversos , Polimorfismo de Nucleótido Simple
3.
Mol Ther ; 30(2): 644-661, 2022 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-34547462

RESUMEN

Preclinical and clinical studies have validated the antitumor effects of several oncolytic viruses (OVs). However, the efficacy of OVs is limited when they are administered as monotherapies. Combination therapy is a promising direction for oncolytic virotherapy in the future. A high dose of vitamin C (VitC) exerts anticancer effects by triggering the accretion of substantial amounts of reactive oxygen species (ROS). OVs can induce immunogenic tumor cell death and elicit an antitumor immune response. ROS play an important role in immunogenic cell death (ICD). This study aimed to explore whether high-dose VitC in combination with oncolytic adenoviruses (oAds) exhibited a synergistic antitumor effect. High-dose VitC synergized with oAds against tumor by enhancing immunogenic tumor cell death. Combination therapy with high-dose VitC and oAds significantly increased the number of T cells in the tumor microenvironment (TME) and promoted the activation of T cells. Furthermore, the antitumor effect of the combination therapy was CD8+ T cell dependent. In addition, combination therapy with high-dose VitC and oAds reprogramed the immunosuppressive TME. Our study provides a new strategy for combination therapy of OVs.


Asunto(s)
Neoplasias , Viroterapia Oncolítica , Virus Oncolíticos , Adenoviridae/genética , Humanos , Muerte Celular Inmunogénica , Neoplasias/terapia , Virus Oncolíticos/fisiología , Microambiente Tumoral
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(3): 969-974, 2021 Jun.
Artículo en Chino | MEDLINE | ID: mdl-34105502

RESUMEN

OBJECTIVE: To investigate the therapeutic effect of spleen low molecular weight extracts on epileptics hydrochloride-induced leukopenia in mice and explore its mechanism. METHODS: The model of leukopenia in mice was established by the injection of epirubicin hydrochloride (10 mg/kg). After the injection of chemotherapeutic drugs, leukocytopenia mice were treated with different doses of spleen low molecular weight extract, Ganoderma oral solution and recombinant granulocyte colony stimulating factor (rhG-CSF). The general survival status indicators such as body weight, coat color and athletic ability of mice in each group were recorded; the tail vein blood of mice in each group was collected and the white blood cell count in them was calculated; bone marrow of mice was taken and bone marrow smears were observed. RESULTS: In the model group, the weight of the mice gradually decreased in the later period, their coat became dark and rough, and the ability to exercise decreased, while the mice in the treatment groups showed different degrees of improvement in their survival status except for the mice treated by rhG-CSF. There was no significant fluctuation in the white blood cell count of the blank control mice. After injection of epirubicin, the white blood cell count of peripheral blood in the model mice and treated mice were decreased. The white blood cell count was lower in the mice treated with high-dose low molecular weight extract and rhG-CSF than that in other experimental groups. Bone marrow smear showed that the proportion of bone marrow nucleated cells in the mice treated with the low molecular weight extract of the spleen was significantly higher than that of model mice (P<0.05). CONCLUSION: The low molecular weight spleen extracts can significantly improve the hematopoietic state of mouse bone marrow, promote the proliferation of inhibited bone marrow cells, and thus has the effect of treating leukopenia in mice.


Asunto(s)
Leucopenia , Bazo , Animales , Epirrubicina , Factor Estimulante de Colonias de Granulocitos , Recuento de Leucocitos , Leucopenia/inducido químicamente , Leucopenia/tratamiento farmacológico , Ratones , Peso Molecular , Extractos Vegetales , Proteínas Recombinantes
5.
Artículo en Chino | WPRIM | ID: wpr-880177

RESUMEN

OBJECTIVE@#To investigate the therapeutic effect of spleen low molecular weight extracts on epileptics hydrochloride-induced leukopenia in mice and explore its mechanism.@*METHODS@#The model of leukopenia in mice was established by the injection of epirubicin hydrochloride (10 mg/kg). After the injection of chemotherapeutic drugs, leukocytopenia mice were treated with different doses of spleen low molecular weight extract, Ganoderma oral solution and recombinant granulocyte colony stimulating factor (rhG-CSF). The general survival status indicators such as body weight, coat color and athletic ability of mice in each group were recorded; the tail vein blood of mice in each group was collected and the white blood cell count in them was calculated; bone marrow of mice was taken and bone marrow smears were observed.@*RESULTS@#In the model group, the weight of the mice gradually decreased in the later period, their coat became dark and rough, and the ability to exercise decreased, while the mice in the treatment groups showed different degrees of improvement in their survival status except for the mice treated by rhG-CSF. There was no significant fluctuation in the white blood cell count of the blank control mice. After injection of epirubicin, the white blood cell count of peripheral blood in the model mice and treated mice were decreased. The white blood cell count was lower in the mice treated with high-dose low molecular weight extract and rhG-CSF than that in other experimental groups. Bone marrow smear showed that the proportion of bone marrow nucleated cells in the mice treated with the low molecular weight extract of the spleen was significantly higher than that of model mice (P<0.05).@*CONCLUSION@#The low molecular weight spleen extracts can significantly improve the hematopoietic state of mouse bone marrow, promote the proliferation of inhibited bone marrow cells, and thus has the effect of treating leukopenia in mice.


Asunto(s)
Animales , Ratones , Epirrubicina , Factor Estimulante de Colonias de Granulocitos , Recuento de Leucocitos , Leucopenia/tratamiento farmacológico , Peso Molecular , Extractos Vegetales , Proteínas Recombinantes , Bazo
6.
Oncotarget ; 7(29): 45513-45524, 2016 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-27322422

RESUMEN

To measure the safety and efficacy of oxaliplatin (OX) application in neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC), EMBASE, PubMed, Cochrane Library, and Web of Science were used for a literature search. Cochrane's risk of bias tool of randomized controlled trials (RCTs) was used for quality evaluation. The statistical analyses were performed using RevMan 5.3. In addition, 95% confidence intervals (CIs) and pooled risk ratios (RRs) were calculated. Seven RCTs were included in our meta-analysis. After adding OX to fluoropyrimidine (FU), a marginal significant improvement in disease-free survival was noted compared with FU alone (RR = 0.89, 95% CI: 0.78-1.00; P = 0.05). Neoadjuvant CRT with OX significantly decreased the distant metastasis rate (RR = 0.79, 95% CI: 0.67-0.94, P = 0.007). However, no improvement in the local recurrence rate (RR = 0.86, 95% CI: 0.68-1.08; P = 0.19) was noted. In addition, neoadjuvant CRT with OX also significantly increased the pathologic complete response (RR = 1.24, 95% CI: 1.02-1.51; P = 0.03). Grade 3-4 acute toxicity and grade 3-4 diarrhea was considerably higher for OX/FU compared with FU alone. In conclusion, the use of OX on the basis of FU/capecitabine in preoperative CRT is feasible. LARC patients are likely to benefit from CRT regimens with OX.


Asunto(s)
Quimioradioterapia Adyuvante/métodos , Terapia Neoadyuvante/métodos , Compuestos Organoplatinos/administración & dosificación , Neoplasias del Recto/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Fluorouracilo/administración & dosificación , Humanos , Oxaliplatino , Neoplasias del Recto/radioterapia
7.
BMC Complement Altern Med ; 14: 89, 2014 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-24602493

RESUMEN

BACKGROUND: Berberine is an isoquinoline alkaloid mainly extracted from Rhizoma Coptidis and has been shown to possess a potent inhibitory activity against bacterial. However, the role of berberine in anti-bacterial action has not been extensively studied. METHODS: The animal model was established to investigate the effects of berberine on bacterial and LPS infection. Docking analysis, Molecular dynamics simulations and Real-time RT-PCR analysis was adopted to investigate the molecular mechanism. RESULTS: Treatment with 40 mg/kg berberine significantly increased the survival rate of mice challenged with Salmonella typhimurium (LT2), but berberine show no effects in bacteriostasis. Further study indicated that treatment with 0.20 g/kg berberine markedly increased the survival rate of mice challenged with 2 EU/ml bacterial endotoxin (LPS) and postpone the death time of the dead mice. Moreover, pretreatment with 0.05 g/kg berberine significantly lower the increasing temperature of rabbits challenged with LPS. The studies of molecular mechanism demonstrated that Berberine was able to bind to the TLR4/MD-2 receptor, and presented higher affinity in comparison with LPS. Furthermore, berberine could significantly suppressed the increasing expression of NF-κB, IL-6, TNFα, and IFNß in the RAW264.7 challenged with LPS. CONCLUSION: Berberine can act as a LPS antagonist and block the LPS/TLR4 signaling from the sourse, resulting in the anti-bacterial action.


Asunto(s)
Antibacterianos/farmacología , Berberina/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Antígeno 96 de los Linfocitos/metabolismo , Receptor Toll-Like 4/metabolismo , Animales , Antibacterianos/química , Antibacterianos/metabolismo , Berberina/química , Berberina/metabolismo , Temperatura Corporal/efectos de los fármacos , Línea Celular , Citocinas/metabolismo , Ratones , Ratones Endogámicos BALB C , Simulación de Dinámica Molecular , Conejos , Infecciones por Salmonella/tratamiento farmacológico , Salmonella typhimurium/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
8.
Int J Biol Macromol ; 49(5): 970-8, 2011 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-21889529

RESUMEN

The aims of this investigation were to develop a procedure to prepare chelerythrine (CHE) loaded O-carboxymethylchitosan (O-CMCS) microspheres by emulsion cross-linking method and optimize the process and formulation variables using response surface methodology (RSM) with a three-level, three-factor Box-Behnken design (BBD). The independent variables studied were O-CMCS/CHE ratio, O/W phase ratio, and O-CMCS concentration, dependent variables (responses) were drug loading content and encapsulation efficiency. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The process and formulation variables were optimized to achieve maximum drug loading content and entrapment efficiency by the desirability function. The optimized microsphere formulation was characterized for particle size, shape, morphology and in vitro drug release. Results for mean particle size, drug loading content, entrapment efficiency, and in vitro drug release of CHE-loaded O-CMCS microspheres were found to be of 12.18 µm, 4.16 ± 3.36%, 57.40 ± 2.30%, and 54.5% at pH 7.4 after 70 h, respectively. The combination use of RSM, BBD and desirability function could provide a promising application for O-CMCS as controlled drug delivery carrier and help to develop procedures for a lab-scale microemulsion process.


Asunto(s)
Benzofenantridinas/química , Química Farmacéutica/métodos , Quitosano/análogos & derivados , Preparaciones de Acción Retardada/química , Portadores de Fármacos/química , Composición de Medicamentos/métodos , Neoplasias/tratamiento farmacológico , Algoritmos , Antineoplásicos/química , Antineoplásicos/farmacología , Benzofenantridinas/farmacología , Quitosano/química , Preparaciones de Acción Retardada/farmacología , Portadores de Fármacos/farmacología , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Concentración de Iones de Hidrógeno , Microscopía Electrónica de Rastreo , Microesferas , Modelos Estadísticos , Tamaño de la Partícula , Análisis de Regresión , Temperatura , Agua
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