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BACKGROUND: ShuGan-QieZhi capsule (SGQZC) is a traditional Chinese preparation used to treat hyperlipidemia and obesity, even non-alcoholic fatty liver disease (NAFLD). However, its therapeutic effects, main bioactive ingredients, as well as potential mechanisms for NAFLD are still unclear. PURPOSE: To investigate the pharmacological effect, main active ingredients, and mechanisms of SGQZC against high-fat diet (HFD)-induced NAFLD in mice. METHODS: NAFLD models were established by feeding C57BL/6 J mice an HFD for 24 weeks. From the 12th week, HFD-fed mice received daily gavage of either SGQZC or silibinin for 12 weeks. Hepatic hypertrophy parameters, along with hepatic and systemic lipid metabolism changes in NAFLD mice, were assessed. Oil red O and histopathological staining techniques determined lipid accumulation and liver injury severity. qRT-PCR analysis measured the expression of genes tied to liver lipid metabolism and inflammation. HPLC-MS/MS identified the primary components of SGQZC in the serum. Human normal hepatocytes (LO2) and hepatic stellate cells (LX-2) were used to screen SGQZC's bioactive ingredients. Network pharmacological analysis, transcriptomics, and western blotting delved into SGQZC's synergistic mechanisms against NAFLD. RESULTS: SGQZC ameliorated abnormal lipid metabolism and liver hypertrophy in mice with HFD-induced NAFLD, consequently reducing hepatic lipid accumulation, inflammatory cell infiltration, and liver impairment. Eight crucial components of SGQZC were detected in serum using HPLC-MS/MS and were found to effectively attenuate lipid accumulation and inflammation in liver cells. Further investigation indicated that SGQZC modulates MAPK pathway and AKT/NF-κB pathway, subsequently improving lipid metabolism and inflammation. CONCLUSION: SGQZC alleviates NAFLD by synergistically modulating the MAPK-mediated lipid metabolism and inhibiting AKT/NF-κB pathways-mediated inflammation. Our findings reveal the enormous potential of SGQZC for the treatment of NAFLD, providing a possible new clinical therapeutic strategy.
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Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espectrometria de Massas em Tandem , Camundongos Endogâmicos C57BL , Fígado , Inflamação/tratamento farmacológico , Metabolismo dos Lipídeos , Dieta Hiperlipídica/efeitos adversos , Lipídeos , Hipertrofia/patologiaRESUMO
BACKGROUND: Gandi capsule is a traditional Chinese herbal formula used to promote blood circulation and removing blood stasis in clinical. Our previous study has shown that it reduces proteinuria with routine treatment in diabetic nephrophy (DN), but its pharmacological action mechanism is still unknown. METHODS: To facilitate the identification of components, a component database of Gandi capsule and target database of DN were established by ourselves. The components absorbed in blood circle were identified in rat plasma after oral administration of Gandi capsule by UHPLC-QQQ-MS/MS. The potential targets were screened by using Libdock tolls in Discovery studio 3.0. Then Pathway and Network analyses were used to enrich the screened targets. The possible targets were verified by using a surface plasmon resonance (SPR) test and the molecular mechanism focusing these targets for treating DN was clarified by western blot. RESULTS: Six components in Gandi capsule were identified detected in rat plasma after oral administration by UHPLC-QQQ-MS/MS. After molecular docking analyses in KEGG and Discovery studio, four protein targets including HNF4A, HMGCR, JAK3, and SIRT1, were screened out, and proved as effective binding with baicalin, wogonoside by SPR. And the molecular mechanism was clarified that baicalin and wogonoside inhibit the effect of high glucose (HG)-induced decreased cell viability and podocin expression, and strengthen the activation p-AKT, p-PI3K, and p-AMPK. CONCLUSION: Baicalin and wogonoside were screened out to be the active compounds in Gandi capsule and can ameliorate HG-induced podocyte damage by influencing the AMPK and PI3K-AKT signaling pathways by binding with HNF4A, HMGCR, JAK3, and SIRT1.
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Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa/métodos , Simulação de Acoplamento Molecular , Mapas de Interação de Proteínas , Animais , Cápsulas , Linhagem Celular , China , Medicamentos de Ervas Chinesas/química , Humanos , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
The room-temperature controlled crystallization of monodispersed ZnS nanoparticles (average size of 5 nm) doped with luminescent ions (such as Mn2+, Eu3+, Sm3+, Nd3+, and Yb3+) was achieved via a microfluidic approach. The preparation did not require any stabilizing ligands or surfactants, minimizing potential sources of impurities. The synthesized nanomaterials were characterized from a structural (XRD and XAS at lanthanide L3 edges), morphological (TEM), and compositional (XPS, ICP-MS) perspective, giving complementary information on the materials' features. In view of potential applications in the field of optical bioimaging, the optical emission properties of the doped nanoparticles were assessed, and samples showed strong luminescent properties while being less affected by self-quenching mechanisms. Furthermore, in vitro cytotoxicity experiments were conducted, showing no negative effects and evidencing the appeal of the synthesized materials for potential applications in the field of optical bioimaging.
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Técnicas Analíticas Microfluídicas , Nanopartículas/química , Imagem Óptica , Sulfetos/química , Elementos de Transição/química , Compostos de Zinco/química , Células A549 , Cristalização , Humanos , Luminescência , Tamanho da Partícula , Propriedades de Superfície , Células Tumorais Cultivadas , Espectroscopia por Absorção de Raios XRESUMO
This study was conducted to reveal the effects of silicon (Si) application on nutrient utilization efficiency by rice and on soil nutrient availability and soil microorganisms in a hybrid rice double-cropping planting system. A series of field experiments were conducted during 2017 and 2018. The results showed that Si nutrient supply improved grain yield and the utilization rates of nitrogen (N) and phosphorus (P) to an appropriate level for both early and late plantings, reaching a maximum at 23.4 kg/ha Si. The same trends were found for the ratios of available N (AN) to total N (TN) and available P (AP) to total P (TP), the soil microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), microbial biomass phosphorus (MBP), and the ratios of MBN to TN and MBP to TP, at different levels of Si. Statistical analysis further revealed that Si application enhanced rice growth and increased the utilization rate of fertilizer due to an ecological mechanism, i.e., Si supply significantly increased the total amount of soil microorganisms in paddy soil compared to the control. This promoted the mineralization of soil nutrients and improved the availability and reserves of easily mineralized organic nutrients.
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Nitrogênio/metabolismo , Oryza/crescimento & desenvolvimento , Fósforo/metabolismo , Silício/metabolismo , Microbiologia do Solo , Agricultura/métodos , Biomassa , Carbono , Fertilizantes , Nutrientes/metabolismo , Solo/químicaRESUMO
BACKGROUND/PURPOSES: Treatment of Staphylococcus aureus infections is challenging owing to widespread multidrug resistance. There is now considerable interest in the potential of combination therapies. Although linezolid/fosfomycin combination appears to be a promising treatment option based on in vitro data, further preclinical work is needed. In this study, the Galleria mellonella system was employed to study the in vivo efficacy of this combination in order to determine whether it should be explored further for the treatment of S. aureus infections. METHODS: The antimicrobial activity of linezolid and fosfomycin alone and in combination was assessed versus four S. aureus. Synergy studies were performed using the microtitre plate chequerboard assay and time-kill methodology. The in vivo activity of linezolid/fosfomycin combination was assessed using a G. mellonella larvae model. RESULTS: The combination of linezolid and fosfomycin was synergistic and bacteriostatic against four tested strains. Treatment of G. mellonella larvae infected with lethal doses of S. aureus resulted in significantly enhanced survival rates when low-dose of combination has no significant differences with high-dose combination (P > 0.05), G. mellonella hemolymph burden of S. aureus suggest that combination therapy with rapid and sustained bacteriostatic activity compared monotherapy. CONCLUSION: This work indicated that linezolid combination with fosfomycin has synergistic effect against S. aureus in vitro and in an experimental G. mellonella model, and it suggests that high-dose of linezolid and fosfomycin may not necessary.
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Antibacterianos/uso terapêutico , Fosfomicina/uso terapêutico , Linezolida/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada , Testes de Sensibilidade Microbiana , MariposasRESUMO
BACKGROUND: Cancer causes millions of deaths and huge economic losses every year. The currently practiced methods for cancer therapy have many defects, such as side effects, low curate rate, and discomfort for patients. OBJECTIVE: Herein, we summarize the applications of gold nanorods (AuNRs) in cancer therapy based on their photothermal effect-the conversion of light into local heat under irradiation. METHODS: The recent advances in the synthesis and regulation of AuNRs, and facile surface functionalization further facilitate their use in cancer treatment. For cancer therapy, AuNRs need to be modified or coated with biocompatible molecules (e.g. polyethylene glycol) and materials (e.g. silicon) to reduce the cytotoxicity and increase their biocompatibility, stability, and retention time in the bloodstream. The accumulation of AuNRs in cancerous cells and tissues is due to the high leakage in tumors or the specific interaction between the cell surface and functional molecules on AuNRs such as antibodies, aptamers, and receptors. RESULTS: AuNRs are employed not only as therapeutics to ablate tumors solely based on the heat produced under laser that could denature protein and activate the apoptotic pathway, but also as synergistic therapies combined with photodynamic therapy, chemotherapy, and gene therapy to kill cancer more efficiently. More importantly, other materials like TiO2, graphene oxide, and silicon, etc. are incorporated on the AuNR surface for multimodal cancer treatment with high drug loadings and improved cancer-killing efficiency. To highlight their applications in cancer treatment, examples of therapeutic effects both in vitro and in vivo are presented. CONCLUSION: AuNRs have potential applications for clinical cancer therapy.
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Ouro , Hipertermia Induzida , Nanotubos , Neoplasias/terapia , Fotoquimioterapia , Linhagem Celular Tumoral , HumanosRESUMO
To improve the detection sensitivity of porous silicon microcavity biosensors, CdSe/ZnS quantum dots are used to label complementary DNA molecules for the refractive index amplification and angular spectrum method for detection. In this method, the TE mode laser is used as the detection light and the light source is changed into a parallel beam by collimating and expanding the beam, which illuminates the PSM surface and receives the reflected light from the PSM surface through the detector. The angle corresponding to the weakest reflected light intensity before and after the biological reaction between probe DNA and complementary DNA of different concentrations labeled by quantum dots was measured by the detector, and the relationship between the angle change before and after the biological reaction and the complementary DNA concentration labeled by quantum dots was obtained. The experimental results show that the angle change increases linearly with increasing complementary DNA concentration. The detection limit of the experiment, as determined by fitting, is approximately 36 pM. The detection limit of this method is approximately 1/300 of that without quantum dot labeling. Our method has a low cost because it does not require the use of a reflectance spectrometer, and it also demonstrates high sensitivity.
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BACKGROUND: Changes in the national drug policy always have impact on the drug utilization. In the context of China health care reform, what changes had happened in the trend of drug utilization in public hospitals? Has this change met the expectations of policy design? This study was conducted to explore the trend of medicine consumption in county public hospitals before and after health care reform, and to provide real-world evidence to help assess the effectiveness of national drug policy. METHODS: A cross-sectional study was performed to investigate the drug utilization trends of 6 county public hospitals in Anhui Province, which is the first pilot area of China health care reform. Data were collected before and after the implementation of the China National Essential Medicine Policy (NEMP) to analyse the drug utilization indicators, such as the drug utilization constituent ratio, the rate of essential medicine usage and the rate of antibiotic consumption. RESULTS: Chemicals are used most frequently and account for 60%~ 70%, followed by oral agents of proprietary Chinese medicine. The results also show increased consumption of Chinese medicine injections (χ2 = 28.428, P < 0.01). The top 3 chemical medicines consumed were anti-infective drugs (12.92%), cardiovascular system drugs (11.61%), and digestive system drugs (8.42%). For Chinese traditional medicine, the top 3 drugs consumed were internal medicine drugs (66.03%), surgical drugs (8.45%), and gynaecological drugs (7.70%). The total sales amounts of drugs covered by medical insurance are at a high level (all above 80%), whereas essential medicines are less than 50% at almost all county-level medical institutions. CONCLUSIONS: This study uncovered the changing tendency of medicine usage under the implementation of the reform. Chinese medicine injections and anti-infective drugs have always been a sustained concern of pharmacovigilance. It is noteworthy that although essential medicines are advocated for as a priority for use in the government-run hospital, the consumption proportion of these medicines is lower than expected.
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Uso de Medicamentos/tendências , Reforma dos Serviços de Saúde/tendências , Hospitais de Condado/tendências , Hospitais Públicos/tendências , Anti-Infecciosos/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , China , Comércio , Estudos Transversais , Medicamentos Essenciais/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Humanos , Farmacovigilância , Projetos PilotoRESUMO
Impaired vascular integrity leads to serious cerebral vascular diseases such as intracerebral hemorrhage (ICH). In addition, high-dose statin therapy is suggested to cause increased ICH risk due to unclear effects of general inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) on the vascular system. Here we evaluated the protective effects of sodium tanshinone IIA sulfonate (STS), which has high efficacy and safety in clinical studies of ischemic stroke, by using atorvastatin (Ator) induced ICH zebrafish embryos and human umbilical vein endothelial cells (HUVECs). By using double transgenic Tg(fli1a:EGFP)y1 & Tg(gata1a:dsRed)sd2 zebrafish, we demonstrated that STS effectively reduced the occurrence and area of hemorrhage induced by Ator in zebrafish and restored impairment in motor function. We further demonstrated that Ator-induced disruption in VE-cadherin (VEC)-containing cell-cell adherens junctions (AJs) in HUVECs by enhancing Src-induced VEC internalization and RhoA/ROCK-mediated cellular contraction. STS inhibited Ator-induced Src activation and subsequent VEC internalization and actin depolymerization near cell borders, reducing lesions between neighboring cells and increasing barrier functions. STS also inhibited the Ator-induced RhoA/ROCK-mediated cellular contraction by regulating downstream LIMK/cofilin and MYPT1/MLC phosphatase signaling. These results showed that STS significantly promoted the stability of cell junctions and vascular integrity. Moreover, we observed that regulations of both Src and RhoA/ROCK are required for the maintenance of vascular integrity, and Src inhibitor (PP2) or ROCK inhibitors (fasudil and H1152) alone could not reduce the occurrence Ator-induced ICH. Taken together, we investigated the underlying mechanisms of Ator-induced endothelial instability, and provided scientific evidences of STS as potential ICH therapeutics by promoting vascular integrity.
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Antígenos CD/metabolismo , Atorvastatina/toxicidade , Caderinas/metabolismo , Hemorragia Cerebral/metabolismo , Endotélio Vascular/metabolismo , Fenantrenos/uso terapêutico , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Animais , Animais Geneticamente Modificados , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/prevenção & controle , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Fenantrenos/farmacologia , Peixe-ZebraRESUMO
Isodeoxyelephantopin (ESI), isolated from Elephantopus scaber L. has been reported to exert anticancer effects. In this study, we aimed to investigate whether and how cancer cells exert protective responses against ESI treatment. Confocal fluorescence microscopy showed that ESI significantly induced autophagy flux in the lung cancer cells expressing mCherry-EGFP-LC3 reporter. Treatment of the cells with ESI increased the expression levels of the autophagy markers including LC3-II, ATG3 and Beclin1 in a dose-dependent manner. Pretreatment with autophagy inhibitor 3-methyladenine (3-MA) not only attenuated the effects of ESI on autophagy, but also enhanced the effects of ESI on cell viability and apoptosis. Mechanistically, the SILAC quantitative proteomics coupled with bioinformatics analysis revealed that the ESI-regulated proteins were mainly involved in Nrf2-mediated oxidative stress response. We found that ESI induced the nuclear translocation of Nrf2 for activating the downstream target genes including HO-1 and p62 (SQSTM1). More importantly, ESI-induced p62 could competitively bind with Keap1, and releases Nrf2 to activate downstream target gene p62 as a positive feedback loop, therefore promoting autophagy. Furthermore, knockdown of Nrf2 or p62 could abrogate the ESI-induced autophagy and significantly enhanced the anticancer effect of ESI. Taken together, we demonstrated that ESI can sustain cell survival by activating protective autophagy through Nrf2-p62-keap1 feedback loop, whereas targeting this regulatory axis combined with ESI treatment may be a promising strategy for anticancer therapy.
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Antineoplásicos Fitogênicos/farmacologia , Autofagia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Lactonas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Células A549 , Transporte Ativo do Núcleo Celular , Apoptose , Asteraceae/química , Proteína Beclina-1/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Biologia Computacional , Humanos , Microscopia Confocal , Estresse Oxidativo , Proteômica , Proteína Sequestossoma-1/metabolismo , Transdução de SinaisRESUMO
Fetal nicotine exposure increased risk of developing cardiovascular disease later in life. The present study tested the hypothesis that perinatal nicotine-induced programming of heart ischemia-sensitive phenotype is mediated by enhanced reactive oxygen species (ROS) in offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from day 4 of gestation to day 10 after birth, in the absence or presence of a ROS inhibitor, N-acetyl-cysteine (NAC) in drinking water. Experiments were conducted in 8 month old age male offspring. Isolated hearts were perfused in a Langendorff preparation. Perinatal nicotine treatment significantly increased ischemia and reperfusion-induced left ventricular injury, and decreased post-ischemic recovery of left ventricular function and coronary flow rate. In addition, nicotine enhanced cardiac ROS production and significantly attenuated protein kinase Cε (PKCε) protein abundance in the heart. Although nicotine had no effect on total cardiac glycogen synthase kinase-3ß (GSK3ß) protein expression, it significantly increased the phosphorylation of GSK3ß at serine 9 residue in the heart. NAC inhibited nicotine-mediated increase in ROS production, recovered PKCε gene expression and abrogated increased phosphorylation of GSK3ß. Of importance, NAC blocked perinatal nicotine-induced increase in ischemia and reperfusion injury in the heart. These findings provide novel evidence that increased oxidative stress plays a causal role in perinatal nicotine-induced developmental programming of ischemic sensitive phenotype in the heart, and suggest potential therapeutic targets of anti-oxidative stress in the treatment of ischemic heart disease.
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Acetilcisteína/uso terapêutico , Antioxidantes/uso terapêutico , Isquemia Miocárdica/etiologia , Nicotina/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Disfunção Ventricular Esquerda/etiologia , Acetilcisteína/administração & dosagem , Animais , Antioxidantes/administração & dosagem , Circulação Coronária/efeitos dos fármacos , Suscetibilidade a Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Feto/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Bombas de Infusão Implantáveis , Masculino , Modelos Biológicos , Isquemia Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Nicotina/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Fenótipo , Fosforilação/efeitos dos fármacos , Gravidez , Proteína Quinase C-épsilon/biossíntese , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Recuperação de Função Fisiológica , Disfunção Ventricular Esquerda/prevenção & controleRESUMO
A gas chromatographic method for simultaneous determination of 50 organochlorine (OCP) and pyrethroid (PP) pesticides in Flos Chrysanthemi was established. Accelerated solvent extraction (ASE) technique was used to extract the target compounds, cleaned with alumina neutral-florisil column, and eluted by mixed solvents of ethyl acetate and hexane (15:85, v/v). Selected pesticides were identified using HP-5 and DB1701 capillary dual column and detected by electron-capture detector. Quantitative analysis was performed using an external standard by HP-5 capillary column. Results showed that recoveries were 73.4-120.1%, and the relative standard deviations (RSDs) were 1.6-12.4%. The limits of detection of the method were 0.0021-0.0069 mg/kg, and the limits of quantity were 0.0064-0.0210 mg/kg.
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Cromatografia Gasosa/métodos , Medicamentos de Ervas Chinesas/química , Resíduos de Praguicidas/análise , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Clorados/química , Hidrocarbonetos Clorados/isolamento & purificação , Limite de Detecção , Modelos Lineares , Resíduos de Praguicidas/química , Resíduos de Praguicidas/isolamento & purificação , Piretrinas/análise , Piretrinas/química , Piretrinas/isolamento & purificação , Reprodutibilidade dos Testes , Extração em Fase SólidaRESUMO
Transient transformation is simpler, more efficient and economical in analyzing protein subcellular localization than stable transformation. Fluorescent fusion proteins were often used in transient transformation to follow the in vivo behavior of proteins. Onion epidermis, which has large, living and transparent cells in a monolayer, is suitable to visualize fluorescent fusion proteins. The often used transient transformation methods included particle bombardment, protoplast transfection and Agrobacterium-mediated transformation. Particle bombardment in onion epidermis was successfully established, however, it was expensive, biolistic equipment dependent and with low transformation efficiency. We developed a highly efficient in planta transient transformation method in onion epidermis by using a special agroinfiltration method, which could be fulfilled within 5 days from the pretreatment of onion bulb to the best time-point for analyzing gene expression. The transformation conditions were optimized to achieve 43.87% transformation efficiency in living onion epidermis. The developed method has advantages in cost, time-consuming, equipment dependency and transformation efficiency in contrast with those methods of particle bombardment in onion epidermal cells, protoplast transfection and Agrobacterium-mediated transient transformation in leaf epidermal cells of other plants. It will facilitate the analysis of protein subcellular localization on a large scale.
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Agrobacterium/metabolismo , Técnicas Genéticas/economia , Cebolas/genética , Cebolas/microbiologia , Epiderme Vegetal/microbiologia , Transformação Genética , Arabidopsis/microbiologia , Biolística , Epiderme Vegetal/citologia , Plantas Geneticamente Modificadas , Reprodutibilidade dos Testes , Frações Subcelulares/metabolismo , Fatores de Tempo , Nicotiana/microbiologiaRESUMO
The combination of immunotherapy and chemotherapy is regarded as a promising approach for the treatment of certain types of cancer. However, the underlying mechanisms need to be fully investigated to guide the design of more efficient protocols for cancer chemoimmunotherapy. It is well known that danger-associated molecular patterns (DAMPs) can activate immune cells, including dendritic cells (DCs), via Toll-like receptors (TLRs); however, the role of DAMPs released from chemical drug-treated tumor cells in the activation of the immune response needs to be further elucidated. Here, we found that colorectal cancer (CRC) cells treated with oxaliplatin (OXA) and/or 5-fluorouracil (5-Fu) released high levels of high-mobility group box 1 (HMGB1) and heat shock protein 70 (HSP70). After OXA/5-Fu therapy, the sera of CRC patients also exhibited increased levels of HMGB1 and HSP70, both of which are well-known DAMPs. The supernatants of dying CRC cells treated with OXA/5-Fu promoted mouse and human DC maturation, with upregulation of HLA-DR, CD80 and CD86 expression and enhancement of IL-1ß, TNF-α, MIP-1α, MIP-1ß, RANTES and IP-10 production. Vaccines composed of DCs pulsed with the supernatants of chemically stressed CRC cells induced a more significant IFN-γ-producing Th1 response both in vitro and in vivo. However, the supernatants of chemically stressed CRC cells failed to induce phenotypic maturation and cytokine production in TLR4-deficient DCs, indicating an essential role of TLR4 in DAMP-induced DC maturation and activation. Furthermore, pulsing with the supernatants of chemically stressed CRC cells did not efficiently induce an IFN-γ-producing Th1 response in TLR4-deficient DCs. Collectively, these results demonstrate that DAMPs released from chemically stressed cancer cells can activate DCs via TLR4 and enhance the induction of an anti-tumor T-cell immune response, delineating a clinically relevant immuno-adjuvant pathway triggered by DAMPs.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Vacinas Anticâncer , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/imunologia , Células Dendríticas/imunologia , Imunoterapia/métodos , Linfócitos T/imunologia , Receptor 4 Toll-Like/metabolismo , Animais , Antígenos CD/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Linhagem Celular Tumoral , Citocinas/metabolismo , Dano ao DNA/imunologia , Células Dendríticas/efeitos dos fármacos , Fluoruracila/administração & dosagem , Proteína HMGB1/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estadiamento de Neoplasias , Transplante de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Receptor 4 Toll-Like/genética , Carga Tumoral , VacinaçãoRESUMO
OBJECTIVE: To observe the therapeutic effect of peripheral nerve adjustment for the treatment of postherpetic neuralgia (PHN). METHODS: One hundred and two patients with PHN were randomly assigned to three groups; the control group (A), the experimental group (B), which was subjected to peripheral nerve adjustment, and patients who received a sham peripheral nerve adjustment, thus serving as a positive control group (C). The patients' Visual Analogue Scale (VAS) and total oral rescue dosage for pain management were recorded at days 1, 3, 7, 14, and 28 following treatment. Quality of life (QOL), 36-Item Short-Form Health Survey (SF-36), and side effects were recorded following treatment. RESULTS: We observed that the average VAS score was significantly lower in the treatment group (B) than in the control groups A and C following treatment (P < 0.05). In addition, the QOL and SF-36 scores for group B improved substantially following treatment compared to groups A and C, and this effect was maintained up to 180 days after treatment (P < 0.05). The average dosage of pain medication was also lower in group B, compared to groups A and C, following treatment (P < 0.05). CONCLUSIONS: We conclude that peripheral nerve adjustment can relieve PHN pain and improve patients' quality of life. The possible mechanisms involved may include the reduction of both peripheral and central sensitization, the modulation of nerve plasticity, and an increase in endogenous analgesic molecules.
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Terapia por Acupuntura/métodos , Neuralgia Pós-Herpética/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Qualidade de Vida , Método Simples-Cego , Resultado do TratamentoAssuntos
Terapia por Acupuntura , Antibacterianos/uso terapêutico , Infecções por Mycoplasma/tratamento farmacológico , Prostatite/terapia , Adulto , Idoso , Doença Crônica/terapia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycoplasma/fisiologia , Infecções por Mycoplasma/complicações , Prostatite/tratamento farmacológico , Prostatite/etiologia , Adulto JovemRESUMO
Objective. The randomized controlled trials (RCTs) on Guanxinning injection (GXN) in treating angina pectoris were published only in Chinese and have not been systematically reviewed. This study aims to provide a PRISMA-compliant and internationally accessible systematic review to evaluate the efficacy of GXN in treating angina pectoris. Methods. The RCTs were included according to prespecified eligibility criteria. Meta-analysis was performed to evaluate the symptomatic (SYMPTOMS) and electrocardiographic (ECG) improvements after treatment. Odds ratios (ORs) were used to measure effect sizes. Subgroup analysis, sensitivity analysis, and metaregression were conducted to evaluate the robustness of the results. Results. Sixty-five RCTs published between 2002 and 2012 with 6064 participants were included. Overall ORs comparing GXN with other drugs were 3.32 (95% CI: [2.72, 4.04]) in SYMPTOMS and 2.59 (95% CI: [2.14, 3.15]) in ECG. Subgroup analysis, sensitivity analysis, and metaregression found no statistically significant dependence of overall ORs upon specific study characteristics. Conclusion. This meta-analysis of eligible RCTs provides evidence that GXN is effective in treating angina pectoris. This evidence warrants further RCTs of higher quality, longer follow-up periods, larger sample sizes, and multicentres/multicountries for more extensive subgroup, sensitivity, and metaregression analyses.
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AIM: To evaluate race differences in the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients using a population pharmacodynamic (PPD) model generated and validated using published clinical efficacy trials. METHODS: Published studies randomized trials with rosuvastatin treatment for at least 4 weeks in hypercholesterolemia patients were used for model building and validation. Population pharmacodynamic analyses were performed to describe the dose-response relationship with the mean values of LDL-C reduction (%) from dose-ranging trials using NONMEM software. Baseline LDL-C and race were analyzed as the potential covariates. Model robustness was evaluated using the bootstrap method and the data-splitting method, and Monte Carlo simulation was performed to assess the predictive performance of the PPD model with the mean effects from the one-dose trials. RESULTS: Of the 36 eligible trials, 14 dose-ranging trials were used in model development and 22 one-dose trials were used for model prediction. The dose-response of rosuvastatin was successfully described by a simple E(max) model with a fixed E(0), which provided a common E(max) and an approximate twofold difference in ED(50) for Westerners and Asians. The PPD model was demonstrated to be stable and predictive. CONCLUSION: The race differences in the pharmacodynamics of rosuvastatin are consistent with those observed in the pharmacokinetics of the drug, confirming that there is no significant difference in the exposure-response relationship for LDL-C reduction between Westerners and Asians. The study suggests that for a new compound with a mechanism of action similar to that of rosuvastatin, its efficacy in Western populations plus its pharmacokinetics in bridging studies in Asian populations may be used to support a registration of the new compound in Asian countries.
Assuntos
Anticolesterolemiantes/farmacologia , LDL-Colesterol/metabolismo , Fluorbenzenos/farmacocinética , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Hipercolesterolemia/tratamento farmacológico , Modelos Biológicos , Pirimidinas/farmacocinética , Sulfonamidas/farmacocinética , Anticolesterolemiantes/uso terapêutico , Ásia , Povo Asiático , LDL-Colesterol/antagonistas & inibidores , Ensaios Clínicos como Assunto , Relação Dose-Resposta a Droga , Etnofarmacologia , Fluorbenzenos/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/etnologia , Pirimidinas/uso terapêutico , Rosuvastatina Cálcica , Sulfonamidas/uso terapêutico , População BrancaRESUMO
OBJECTIVE: To evaluate the antioxidant activity of astragalus and its therapeutic effect on gestational diabetes. METHODS: Eighty-four pregnant women with gestational diabetes were divided into insulin and insulin plus astragalus groups after regular dietary control and insulin treatment to maintain stable blood glucose level. The 43 patients in insulin group received insulin injection, whereas the 41 patients in the other group received treatment with both insulin and astragalus. The SOD activity, MDA level, blood lipids and renal function were determined in both groups after the treatments. RESULTS: The patients with both insulin and astragalus treatments showed significantly increased serum SOD activity and decreased MDA level, renal function and blood lipids in comparison with those with exclusive insulin treatment. CONCLUSION: Astragalus can effectively control blood glucose, reduce the free radicals, and promote the antioxidative activity, and may play a role in the prevention and treatment of gestational diabetes.
Assuntos
Antioxidantes/metabolismo , Astrágalo , Diabetes Gestacional/tratamento farmacológico , Diabetes Gestacional/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Fitoterapia , Feminino , Humanos , Malondialdeído/metabolismo , Oxirredução , Gravidez , Superóxido Dismutase/metabolismo , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the therapeutic effect of acupuncture on disorders of myometrial gland and the mechanism. METHODS: Sixty-six cases were randomly divided into an acupuncture group and a medication group, 33 cases in each group. The acupuncture group were treated with acupuncture at Zhongji (CV 3), Shuidao (ST 28), Tainshu (ST 25), Qugu (CV 2), Zigong (EX-CA 1) as main; the medication group were treated with oral administration of Danazol. Changes of estradiol (E2) level, hemoglobin (Hb) and blood platelet counter (BPC) were observed in the acupuncture group, and the therapeutic effects of the two group were compared. RESULTS: The total effective rate was 97.0% in the acupuncture group and 72.7% in the medication group, the former being better than the latter (P<0.05). After treatment, E2 level decreased and Hb and BPC increased in the acupuncture group. CONCLUSION: Acupuncture has obvious therapeutic effect, which is better than that of simple western medicine. Acupuncture can decrease E2 level.