Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
Mais filtros

Medicinas Complementares
Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Biomed Pharmacother ; 161: 114420, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36812713

RESUMO

Breast cancer has been confirmed to have lipid disorders in the tumour microenvironment. Peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcriptional factor that belongs to the family of nuclear receptors. PPARα regulates the expression of genes involved in fatty acid homeostasis and is a major regulator of lipid metabolism. Because of its effects on lipid metabolism, an increasing number of studies have investigated the relationship of PPARα with breast cancer. PPARα has been shown to impact the cell cycle and apoptosis in normal cells and tumoral cells through regulating genes of the lipogenic pathway, fatty acid oxidation, fatty acid activation, and uptake of exogenous fatty acids. Besides, PPARα is involved in the regulation of the tumour microenvironment (anti-inflammation and inhibition of angiogenesis) by modulating different signal pathways such as NF-κB and PI3K/AKT/mTOR. Some synthetic PPARα ligands are used in adjuvant therapy for breast cancer. PPARα agonists are reported to reduce the side effects of chemotherapy and endocrine therapy. In addition, PPARα agonists enhance the curative effects of targeted therapy and radiation therapy. Interestingly, with the emerging role of immunotherapy, attention has been focused on the tumour microenvironment. The dual functions of PPARα agonists in immunotherapy need further research. This review aims to consolidate the operations of PPARα in lipid-related and other ways, as well as discuss the current and potential applications of PPARα agonists in tackling breast cancer.


Assuntos
Neoplasias da Mama , PPAR alfa , Humanos , Feminino , PPAR alfa/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Fosfatidilinositol 3-Quinases/metabolismo , Regulação da Expressão Gênica , Metabolismo dos Lipídeos , Ácidos Graxos/metabolismo , Microambiente Tumoral
2.
Bioresour Technol ; 368: 128311, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36370940

RESUMO

Black phosphorus (BP) and BP modified by hydrogen peroxide (MBP) were used as accelerants to enhance CH4 production and CO2 reduction in microbial electrolysis cells (MECs) coupled with anaerobic co-digestion systems (MEC-AcoD). The MEC-AcoD group with a voltage of 0.6 V and 0.03 wt.% of MBP accelerant (MEC0.6MBP0.03) had the largest CH4 yield (242.1 mL/g VS) and the smallest carbon dioxide yield (97.6 mL/g VS) compared with the control group (141.2 mL/g VS, 146.9 mL/g VS). The digestates that used MEC0.6MBP0.03 exhibited superior thermal stability (46.2 %) and total nutrient contents (44.5 g/kg). These improvements may be attributed to the superior electron exchange capacity and physicochemical properties of MBP. Herein, we propose a strategy to understand enhanced CH4 production and CO2 reduction in anaerobic co-digestion and MEC-AcoD systems using MBP accelerants. Notably, combining MBP and MEC could effectively promote anaerobic co-digestion performance.


Assuntos
Reatores Biológicos , Metano , Anaerobiose , Fósforo , Dióxido de Carbono , Digestão
3.
Front Pharmacol ; 13: 1078303, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36569329

RESUMO

Ovarian cancer is among the most common malignant tumors in gynecology and is characterized by insidious onset, poor differentiation, high malignancy, and a high recurrence rate. Numerous studies have shown that poly ADP-ribose polymerase (PARP) inhibitors can improve progression-free survival (PFS) in patients with BRCA-mutated ovarian cancer. With the widespread use of BRCA mutation and PARP inhibitor (PARPi) combination therapy, the side effects associated with BRCA mutation and PARPi have garnered attention worldwide. Mutations in the BRCA gene increase KEAP1-NRF2 ubiquitination and reduce Nrf2 content and cellular antioxidant capacity, which subsequently produces side effects such as cardiovascular endothelial damage and atherosclerosis. PARPi has hematologic toxicity, producing thrombocytopenia, fatigue, nausea, and vomiting. These side effects not only reduce patients' quality of life, but also affect their survival. Studies have shown that natural phytochemicals, a class of compounds with antitumor potential, can effectively prevent and treat the side effects of chemotherapy. Herein, we reviewed the role of natural phytochemicals in disease prevention and treatment in recent years, including sulforaphane, lycopene, catechin, and curcumin, and found that these phytochemicals have significant alleviating effects on atherosclerosis, nausea, and vomiting. Moreover, these mechanisms of action significantly correlated with the side-effect-producing mechanisms of BRCA mutations and PARPi. In conclusion, natural phytochemicals may be effective in alleviating the side effects of BRCA mutant ovarian cancer cells and PARP inhibitors.

4.
Genes (Basel) ; 13(11)2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36360231

RESUMO

Flavonoids and caffeine are the major secondary metabolites with beneficial bioactivity for human health in tea plants, and their biosynthesis pathway and regulatory networks have been well-deciphered. However, the accumulation traits of flavonoids and caffeine in different tea cultivars was insufficient in investigation. In this study, metabolomic and transcriptomic analyses were performed to investigate the differences of flavonoids and caffeine accumulation and regulation between Chinese varieties, including the 'BTSC' group with green leaf, the 'BTZY' group with purple foliage, and the 'MYC' group comprising Assam varieties with green leaf. The results showed that most of the flavonoids were down-regulated in the 'MYC' group; however, the total anthocyanin contents were higher than that of the 'BTSC' group while lower than that of the 'BTZY' group. An ANS (Anthocyanin synthase) was significantly up-regulated and supposed to play a key role for anthocyanin accumulation in the 'BTZY' group. In addition, the results showed that esterified catechins were accumulated in the 'BTSC' and 'BTZY' groups with high abundance. In addition, SCPL1A (Type 1A serine carboxypeptidase-like acyltransferases gene) and UGGT (UDP glucose: galloyl-1-O-ß-d-glucosyltransferase gene) potentially contributed to the up-accumulation of catechins esterified by gallic acid. Interestingly, the results found that much lower levels of caffeine accumulation were observed in the 'MYC' group. RT-qPCR analysis suggested that the expression deficiency of TCS1 (Tea caffeine synthase 1) was the key factor resulting in the insufficient accumulation of caffeine in the 'MYC' group. Multiple MYB/MYB-like elements were discovered in the promoter region of TCS1 and most of the MYB genes were found preferentially expressed in 'MYC' groups, indicating some of which potentially served as negative factor(s) for biosynthesis of caffeine in tea plants. The present study uncovers the characteristics of metabolite accumulation and the key regulatory network, which provide a research reference to the selection and breeding of tea varieties.


Assuntos
Camellia sinensis , Catequina , Humanos , Camellia sinensis/genética , Camellia sinensis/metabolismo , Cafeína/metabolismo , Flavonoides , Transcriptoma , Antocianinas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Melhoramento Vegetal , Catequina/metabolismo , Chá/genética , China
5.
Aging Male ; 25(1): 219-227, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35989611

RESUMO

BACKGROUND: Solitary fibrous tumor (SFT) is a relatively rare type of mesenchymal neoplasm that occurs most frequently in the pleura. However, SFT originating from the prostate is particularly uncommon and only approximately 39 cases were reported before. Herein, we reported a rare case of a patient diagnosed with prostate SFT and presented a literature review.Case presentation: A 50-year-old Asian with irritative urinary symptoms was admitted to our hospital and almost all the evidence indicated that benign prostate hyperplasia (BPH) caused his symptoms. Therefore, transurethral resection of the prostate (TURP) was performed, but histopathological and Immunohistochemical (IHC) assessments showed that spindle cells arranged disorderly in the TURP specimen with a cluster of differentiation 34 (CD34), B-cell lymphoma-2 (Bcl-2), and signal transducer and activator of transcription 6 (STAT6) highly expressed and SFT was diagnosed. Finally, the patient underwent a radical prostatectomy and there was no disease progression observed thereafter. CONCLUSIONS: Prostate SFT is extremely rare, and to our knowledge, this is the first case of prostate SFT that is difficult to differentiate from small volume BPH. IHC examinations are of great diagnostic value. Radical resection of the tumor appears to be the most effective method at present and continuous follow-up is highly recommended.


Assuntos
Hiperplasia Prostática , Neoplasias da Próstata , Tumores Fibrosos Solitários , Ressecção Transuretral da Próstata , Humanos , Masculino , Próstata/patologia , Próstata/cirurgia , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/cirurgia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Tumores Fibrosos Solitários/diagnóstico , Tumores Fibrosos Solitários/patologia , Tumores Fibrosos Solitários/cirurgia
6.
Animals (Basel) ; 12(14)2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35883361

RESUMO

Based on the randomized design, a 3 × 3 factorial experiment was designed to examine the effects of dietary calcium (Ca), phosphorus (P), and vitamin D3 (VD3) supplemental levels with a fixed 1.5/1 ratio of Ca to P on the growth performance, nutrient digestibility, and serum biochemical indices blue foxes' growth. In total, 135 male blue foxes with the age of 60 days were randomly divided into 9 groups each with 15 blue foxes. The blue foxes belonging to the nine treatment groups were fed Ca supplementation (0%, 0.4%, or 0.8%) and VD3 supplementation (1000, 2000, or 4000 IU/kg DM). The base diet contained 0.8% Ca and 327 IU/kg VD3. The dosage of VD3 in blue foxes showed a significant impact on their growth performance (p < 0.05). The Ca dosage had a linear effect on the digestibility of the CP and carbohydrates (CHO) (p < 0.05). In conclusion, the results indicated that the Ca and VD3 doses showed promising effects on growth performance and nutrient digestibility in growing blue foxes and could reduce fecal N and P via improvement in protein and P utilization.

7.
J Med Food ; 25(3): 261-271, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35320010

RESUMO

Diosgenin (DIO) is a kind of steroid sapogenin derived from natural plants. It exerts strong anti-infection, antiallergy, antiviral, and antishock pharmacological properties. In this article, the protective effects of DIO against dextran sulfate sodium (DSS)-induced colitis in mice were researched. Compared with the 2.5% DSS treatment group, 15 mg/kg body weight of diosgenin alleviated colitis disease, evidenced by the increased body weight, the decrease in the disease activity index, and the histological scores. Furthermore, 16S rRNA high-throughput sequencing results demonstrated that DIO improved the colon homeostasis through modulating the gut microbiota, including increases in the relative abundance of several probiotic bacteria, such as Prevotellaceae (from 1.4% to 5.8%), Lactobacillus (from 12.3% to 29.7%), Mucispirillum (from 0.07% to 0.49%), and decreases in the pathogenic bacteria, such as Streptococcus (from 1.6% to 0.6%) and Pseudomonadaceae (from 0.004% to 0%). In addition, the concentration of gut microbial metabolites, total short-chain fatty acids (SCFAs), acetic acid, and propionic acid were significantly increased after DIO supplementation. In conclusion, our findings suggested that DIO attenuates DSS-induced colitis in mice by means of modulating imbalanced gut microbiota and increases in SCFA generation.


Assuntos
Colite , Diosgenina , Microbioma Gastrointestinal , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Sulfato de Dextrana/efeitos adversos , Ácidos Graxos Voláteis/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S/genética
8.
Br J Nutr ; 128(11): 2083-2096, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-35057874

RESUMO

Vitamin D (VD) plays a vital role in various physiological processes in addition to its classic functions on maintaining the balance of Ca and P metabolism. However, there still are gaps to understand in depth the issues on the precise requirement, metabolic processes and physiological functions of VD in fish. In this study, we investigated the effects of VD on the growth, intestinal health, host immunity and metabolism in turbot (Scophthalmus maximus L.), one important commercial carnivorous fish in aquaculture, through the supplementation of different doses of dietary VD3 (0, 200, 400, 800 and 1600 µg VD3/kg diet). According to our results, the optimal VD3 level in the feed for turbot growth was estimated to be around 400 IU/kg, whereas VD3 deficiency or overdose in diets induced the intestinal inflammation, lowered the diversity of gut microbiota and impaired the host resistance to bacterial infection in turbot. Moreover, the level of 1α,25(OH)2D3, the active metabolite of VD3, reached a peak value in the turbot serum in the 400 µg group, although the concentrations of Ca and phosphate in the turbot were stable in all groups. Finally, the deficiency of dietary VD3 disturbed the nutritional metabolism in turbot, especially the metabolism of lipids and glucose. In conclusion, this study evaluated the optimal dose of dietary VD3 for turbot and provided the evidence that VD has a significant impact on intestinal health, host immunity and nutritional metabolism in fish, which deepened our understanding on the physiological functions and metabolism of VD3 in fish.


Assuntos
Linguados , Microbioma Gastrointestinal , Animais , Vitamina D/farmacologia , Linguados/microbiologia , Intestinos , Dieta
9.
Food Chem ; 377: 132003, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35008025

RESUMO

The long-term cultivation of tea plants without fertilization can severely decrease yield, but it remains unclear whether this soil nutrient deficiency affects tea quality. In this study, tea plants (Camellia sinensis (L.) Kuntze) cultivated in unfertilized soil for 11 years were analyzed. The soil nutrient deficiency down-regulated protochlorophyllide oxidoreductase-encoding gene expression, which adversely affected chlorophyll biosynthesis, ultimately leading to leaf etiolation. Because of decreased synthesis and increased degradation in response to nutrient deficiency, l-theanine content decreased to 11.4% of the control level, which increased the phenol-ammonia ratio and decreased taste quality. Soil nutrient deficiency also decreased the abundance of many aroma compounds (e.g., green leaf volatile, linalool and its oxides, and methyl salicylate). Thus, nutrient deficiency adversely influences tea color, taste, and aroma. This study provides researchers and tea growers with important information regarding the effects of soil nutrient deficiency on tea quality and the rational fertilization of tea gardens.


Assuntos
Camellia sinensis , Nutrientes , Folhas de Planta , Solo , Chá
10.
Fish Shellfish Immunol ; 118: 25-33, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34450270

RESUMO

Accumulating evidence supports that vitamin D3 (VD3) possesses immunomodulatory properties besides its classical actions in calcium and bone homeostasis. In this study, juvenile turbots were fed with the diets containing 0 IU/kg VD3 or the optimum dose of 400 IU/kg VD3 for 8 weeks. To investigate the effects of VD3 on anti-infectious immunity in fish, 107 CFU Edwardsiella tarda was injected intraperitoneally to each juvenile turbot after the feeding trial. Our results showed that the mortality of infected turbots with dietary VD3 was much lower than that in VD3 deficient group, and the supplementation of dietary VD3 significantly reduced the bacterial load in the spleen of infected turbots. Further analysis demonstrated that the production of reactive oxygen species (ROS) in haemocytes and lysozyme activity in serum was elevated, and the responses of T cells and B cells were modulated in VD3-supplemented turbots. Moreover, the inflammation was significantly exacerbated in the infected turbots fed with 0 IU/kg VD3 compared to the fish fed with 400 IU/kg VD3. In addition, the head kidney macrophages (HKMs) in turbots were isolated and incubated with VD3in vitro, the results showed that VD3 significantly promoted the bactericidal activity in HKMs. In conclusion, our study has shown clear evidence that VD3 positively regulates the innate and adaptive immunity in fish, which is beneficial to the defense in fish against pathogen infection.


Assuntos
Infecções Bacterianas , Doenças dos Peixes , Linguados , Animais , Infecções Bacterianas/tratamento farmacológico , Colecalciferol/farmacologia , Suplementos Nutricionais , Edwardsiella tarda , Doenças dos Peixes/tratamento farmacológico , Doenças dos Peixes/microbiologia , Linguados/microbiologia
11.
Chin Med ; 16(1): 16, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33526051

RESUMO

BACKGROUND: Shikonin (SKO) is a natural naphthoquinone derived from Chinese herbal medicine Arnebiae Radix with high development potentials due to its anti-inflammatory and anti-tumor activities. Overwhelming evidences have indicated that SKO can induce both necrosis and apoptosis in cancer cells, while the mechanisms for triple negative breast cancer cells is still need to be disclosed. METHODS: In this study, kinds of molecular biological technologies, including flow-cytometry, Western blot, immunoprecipitation, enzyme-linked immunosorbent assay (ELISA) as well as real-time quantitative PCR (RT-qPCR), were applied for investigation on the underlying mechanisms of SKO induced necrosis and apoptosis for MDA-MB-231 cells. Inhibitors were also used for validation ofthe key signaling pathways involved in SKO triggered necrosis and apoptosis. RESULTS: We found that SKO significantly triggered necrosis and apoptosis of MDA-MB-231 cells in both a concentration- and time-dependent manner. Mechanism studies demonstrated that SKO significantly promoted the autoubiquitination levels and facilitated the proteasome dependent degradation of cellular inhibitor of apoptosis protein 1 (cIAP1) and cIAP2 in MDA-MB-231 cells. Autoubiquitination and degradation of cIAP1 and cIAP2 induced by SKO further led to significant decreased ubiquitination and inactivation of RIP1, which played an important role in inhibition of pro-survival and accelerating of necrosis of MDA-MB-231 cells. Treatment with proteasome inhibitor lactacystin significantly rescued the cell viability induced by treatment of SKO. CONCLUSIONS: Our results demonstrate that SKO promotes the autoubiquitination and degradation of cIAP1 and cIAP2, which further induces the decrease of the ubiquitination of RIP1 to inhibit the activation of pro-survival signaling pathways and accelerate the necrosis of MDA-MB-231 cells. The disclosed mechanisms of SKO induced necrosis and apoptosis in our study is firstly reported, and it is believed that SKO could be considered as a potential candidate and further developed for the treatment of triple negative breast cancer.

12.
J Thromb Thrombolysis ; 50(3): 697-714, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32040703

RESUMO

Oral anticoagulants (OACs) are high alert medications and require high-quality management to optimize health outcomes. The objective of this scoping review was to identify barriers and facilitators (B&Fs) associated with the quality of OAC management. We searched MEDLINE, EMBASE, and CINAHL databases until July 12, 2018, and cross-referenced the bibliographies of the retrieved studies. We included quantitative and qualitative studies that assessed B&Fs to OAC management. The study selection and data extraction processes were performed in duplicate. Analyses included measuring the prevalence of reported B&Fs from studies reporting quantitative data, identifying B&Fs in narrative analyses, and identifying their impact on important outcomes of OAC management. B&Fs were coded and aggregated to higher-level themes using a consensus approach. Factors were described as "key" if they were statistically associated with important outcomes in a randomized trial or observational study. We included 62 studies-three randomized clinical trials (RCTs), 46 observational studies (cross-sectional studies, cohort studies, and case-control studies), 11 qualitative studies, and two mixed-methods studies. Factors identified could be grouped into four themes-therapy-related, patient-related, healthcare provider-related, and health system-related. Key barriers to optimal OAC management were mostly patient-related, whereas interventions focused on education or implementing protocols were shown through RCTs to be effective at improving knowledge scores of OAC patients. While multiple barriers and some facilitators were identified in this review, none was proven to be associated with clinical outcomes. With this in mind, individual physicians may wish to address the key barriers in their practice as a quality improvement initiative but system-wide or policy changes should await high-quality evidence. Future trials should address these factors.Systematic review registration: PROSPERO CRD42017069043.


Assuntos
Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Vitamina K/antagonistas & inibidores , Anticoagulantes/efeitos adversos , Dabigatrana/efeitos adversos , Dabigatrana/uso terapêutico , Gerenciamento Clínico , Inibidores do Fator Xa/efeitos adversos , Humanos , Qualidade da Assistência à Saúde , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico , Tromboembolia/prevenção & controle , Varfarina/efeitos adversos , Varfarina/uso terapêutico
13.
Apoptosis ; 22(11): 1454-1460, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28916869

RESUMO

Protective effect of protodioscin or methyl protodioscin against inflammation had been reported in various inflammation diseases. This study aimed to investigate the effect of protodioscin against Complete Freund's adjuvant (CFA)-induced arthritis rats. Rats randomly divided into model groups were injected with CFA, companied with different dose of protodioscin (50, 100, and 200 mg/kg body weight). The histology, changes in biochemical parameters and inflammatory cytokines expression were detected for anti-inflammation effect evaluation of protodioscin. CFA treatment induced arthritic rats with swelling paw, ankle inflammation, and area of lymphocyte infiltration, upregulated inflammatory cytokines (IL-1ß, TNF-α, cyclo-oxygenase 2, and IL-6 as well as prostaglandin E2), articular elastase, myeloperoxidase, lipid peroxidase and nitrite oxide levels, downregulated glutathione, catalase, and superoxide dismutase. In contrast, protodioscin ameliorated all the changes induced by CFA in rats, suggesting the anti-inflammatory effect of protodioscin. We concluded that protodioscin administration into CFA-induced arthritis rats protected against CFA-induced oxidative stress, neutrophil infiltration, and inflammation, suggesting the anti-inflammatory effect and the therapeutic potential of protodioscin for arthritis.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Experimental/tratamento farmacológico , Diosgenina/análogos & derivados , Edema/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Saponinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Artrite Experimental/induzido quimicamente , Artrite Experimental/genética , Artrite Experimental/patologia , Catalase/genética , Catalase/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Diosgenina/farmacologia , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/genética , Edema/patologia , Adjuvante de Freund/administração & dosagem , Glutationa/metabolismo , Membro Posterior , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Óxido Nítrico/metabolismo , Estresse Oxidativo , Elastase Pancreática/genética , Elastase Pancreática/metabolismo , Peroxidase/genética , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
14.
J Control Release ; 221: 62-70, 2016 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-26551344

RESUMO

Sorafenib is a tyrosine kinase inhibitor that has recently been shown to be a potential antifibrotic agent. However, a narrow therapeutic window limits the clinical use and therapeutic efficacy of sorafenib. Herein, we have developed and optimized nanoparticle (NP) formulations prepared from a mixture of poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PEG-PLGA) copolymers with poly(lactic-co-glycolic acid) (PLGA) for the systemic delivery of sorafenib into the fibrotic livers of CCl4-induced fibrosis mouse models. We characterized and compared the pharmaceutical and biological properties of two different PLGA nanoparticles (NPs)--PEG-PLGA NPs (PEG-PLGA/PLGA=10/0) and PEG-PLGA/PLGA NPs (PEG-PLGA/PLGA=5/5). Increasing the PLGA content in the PEG-PLGA/PLGA mixture led to increases in the particle size and drug encapsulation efficacy and a decrease in the drug release rate. Both PEG-PLGA and PEG-PLGA/PLGA NPs significantly prolonged the blood circulation of the cargo and increased the uptake by the fibrotic livers. The systemic administration of PEG-PLGA or PEG-PLGA/PLGA NPs containing sorafenib twice per week for a period of 4 weeks efficiently ameliorated liver fibrosis, as indicated by decreased α-smooth muscle actin (α-SMA) content and collagen production in the livers of CCl4-treated mice. Furthermore, sorafenib-loaded PLGA NPs significantly shrank the abnormal blood vessels and decreased microvascular density (MVD), leading to vessel normalization in the fibrotic livers. In conclusion, our results reflect the clinical potential of sorafenib-loaded PLGA NPs for the prevention and treatment of liver fibrosis.


Assuntos
Portadores de Fármacos/química , Cirrose Hepática/tratamento farmacológico , Fígado/efeitos dos fármacos , Nanopartículas/química , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Polietilenoglicóis/química , Poliglactina 910/química , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Tetracloreto de Carbono , Células Endoteliais da Veia Umbilical Humana , Ácido Láctico/química , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Camundongos , Nanopartículas/ultraestrutura , Niacinamida/administração & dosagem , Niacinamida/uso terapêutico , Compostos de Fenilureia/administração & dosagem , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Inibidores de Proteínas Quinases/administração & dosagem , Sorafenibe
15.
Biomaterials ; 67: 194-203, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26218745

RESUMO

Sorafenib, a multikinase inhibitor, has been used as an anti-angiogenic agent against highly vascular hepatocellular carcinoma (HCC) - yet associated with only moderate therapeutic effect and the high incidence of HCC recurrence. We have shown intratumoral hypoxia induced by sorafenib activated C-X-C receptor type 4 (CXCR4)/stromal-derived factor 1α (SDF1α) axis, resulting in polarization toward a tumor-promoting microenvironment and resistance to anti-angiogenic therapy in HCC. Herein, we formulated sorafenib in CXCR4-targeted lipid-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) modified with a CXCR4 antagonist, AMD3100 to systemically deliver sorafenib into HCC and sensitize HCC to sorafenib treatment. We demonstrated that CXCR4-targeted NPs efficiently delivered sorafenib into HCCs and human umbilical vein endothelial cells (HUVECs) to achieve cytotoxicity and anti-angiogenic effect in vitro and in vivo. Despite the increased expression of SDF1α upon the persistent hypoxia induced by sorafenib-loaded CXCR4-targeted NPs, AMD3100 attached to the NPs can block CXCR4/SDF1α, leading to the reduced infiltration of tumor-associated macrophages, enhanced anti-angiogenic effect, a delay in tumor progression and increased overall survival in the orthotopic HCC model compared with other control groups. In conclusion, our results highlight the clinical potential of CXCR4-targeted NPs for delivering sorafenib and overcoming acquired drug resistance in liver cancer.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ácido Láctico/química , Lipídeos/química , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/química , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Ácido Poliglicólico/química , Receptores CXCR4/metabolismo , Animais , Carcinoma Hepatocelular/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Endocitose/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Nanopartículas/ultraestrutura , Metástase Neoplásica , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Fenótipo , Compostos de Fenilureia/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Sorafenibe , Análise de Sobrevida , Microambiente Tumoral/efeitos dos fármacos
16.
Environ Sci Technol ; 48(1): 607-14, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24313712

RESUMO

This field research investigated the water quality performance of a traditional bioretention cell retrofitted with 5% (by mass) water treatment residual (WTR) for enhanced phosphorus removal. Results indicate that WTR incorporation into the bioretention media does not negatively influence the infiltration mechanism of the bioretention system. Total suspended solids (TSS), total phosphorus (TP), and particulate phosphorus (PP) concentrations in runoff inflow were significantly reduced compared to outflow due to filtration of particulate matter. TP concentrations were significantly reduced by the bioretention cell; before WTR retrofit TP export occurred. Although net removal of soluble reactive phosphorus (SRP) and dissolved organic phosphorus (DOP) from incoming runoff was not found, leaching of dissolved phosphorus (DP) was prevented not only from incoming runoff, but also from the media and captured PP. Near constant outflow SRP and DOP concentrations suggest an equilibrium adsorption treatment mechanism. Both event mean concentrations and mass loads were reduced for TSS and all P species. Pollutant mass removals were higher than the event mean concentration removals due to the attenuation of volume by the bioretention media.


Assuntos
Fósforo/análise , Chuva , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Qualidade da Água , Adsorção , Biodegradação Ambiental , Precipitação Química , Filtração , Modelos Químicos , Transição de Fase , Solubilidade , Movimentos da Água
17.
Fish Shellfish Immunol ; 34(5): 1085-93, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23403155

RESUMO

Nodularin is one of the most conspicuous and widespread pollutants that elicit water ecological hazards to fish, causing serious damage on the immune system and physiological functions. Nodularin can cause oxidative stress-induced apoptosis on fish lymphocytes. The regulatory effects of epigallocatechin-3-gallate (EGCG) at 10, 100, and 1000 µg/L levels on the antioxidant defense system and apoptosis of Carassius auratus lymphocytes exposed to a high dose of nodularin (100 µg/L) were quantified in vitro. EGCG reduced nodularin-induced oxidative damage on fish immune cells. This compound significantly increased the activities of superoxide dismutase and catalase and the level of glutathione but decreased the levels of intracellular reactive oxygen species and malondialdehyde. Flow cytometry results showed that the percentages of apoptotic cells after treatment with 10, 100, and 1000 µg/L EGCG for 12 h reached 27.9%, 19.1%, and 13.7%, respectively. By contrast, the nodularin alone-induced group showed a high percentage of apoptosis (44.2%). Western blot analysis showed the increased expression of bcl-2 and the decreased expression of bax and caspase-3 in EGCG-treated fish lymphocytes. EGCG also inhibited the potential collapse of the mitochondrial membrane. Overall, EGCG can inhibit nodularin-induced apoptosis and protect the normal immunity of fish by regulating bax/bcl-2 and blocking the downstream of mitochondrial apoptosis pathway with increased intracellular antioxidant enzyme activity.


Assuntos
Antioxidantes/metabolismo , Catequina/análogos & derivados , Carpa Dourada/metabolismo , Linfócitos/efeitos dos fármacos , Peptídeos Cíclicos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Apoptose/efeitos dos fármacos , Western Blotting/veterinária , Catequina/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Citometria de Fluxo/veterinária , Linfócitos/citologia , Linfócitos/metabolismo , Masculino , Toxinas Marinhas/toxicidade , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Nodularia/química , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
18.
Zhongguo Zhong Yao Za Zhi ; 38(19): 3368-72, 2013 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-24422410

RESUMO

To determine the concentration of gastrodigenin in tissue homogenates with high performance liquid chromatography (HPLC) , in order to study the changes of the distribution of gastrodigenin before and after combined application in rat tissues, including heart, liver, spleen, lung, kidney and brain tissues. The study showed that gastrodigenin could be found in kidney, liver, heart, lungs, spleen and brain tissues. After the combined application of Gastrodiae Rhizoma and Ligustici Wallichii Rhizoma, the content of gastrodigenin decreased in kidney and liver to varying degrees, while increasing in lung and brain. This indicated that Ligustici Wallichii Rhizoma had certain impact on the in vivo distribution of gastrodigenin, an active ingredient in Gastrodiae Rhizoma, because it could improve gastrodigenin's distribution in lung and brain tissues. The study provides scientific basis for the combined application of Gastrodiae Rhizoma and Ligustici Wallichii Rhizoma in treating brain diseases.


Assuntos
Álcoois Benzílicos/farmacocinética , Animais , Álcoois Benzílicos/metabolismo , Encéfalo/metabolismo , Cromatografia Líquida de Alta Pressão , Feminino , Gastrodia/química , Rim/metabolismo , Ligusticum/química , Fígado/metabolismo , Pulmão/metabolismo , Masculino , Ratos , Baço/metabolismo
19.
Zhonghua Yi Shi Za Zhi ; 42(4): 226-30, 2012 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-23336279

RESUMO

Before discussion of the editions of Zhenglei Bencao, the relation between the book and its circulating editions (including the features of those editions) should be investigated. Those circulating editions should include preface and materia medica systematics. Their contents should include the text and figures from Bencao Tujing, text from Jiayou Bencao and contents added by TANG. According to the features above, it was found that Shaoxing Bencao was not the circulating edition of Zhenglei Bencao while Xinbian Leiyao Tuzhu Bencao was.

20.
Am J Clin Nutr ; 95(2): 367-73, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22205314

RESUMO

BACKGROUND: The beneficial health effects associated with Universal Salt Iodization are well known. Yet, little is known about the possible adverse health effects in people with high iodine intake and the safe daily intake upper limit in the Chinese population. OBJECTIVE: The objective of this study was to explore the safe upper level of total daily iodine intake among adults in China. DESIGN: A 4-wk, double-blind, placebo-controlled, randomized controlled trial was conducted in 256 euthyroid adults. Participants were randomly assigned to 12 intervention groups with various iodine supplement doses ranging from 0 to 2000 µg/d. Total iodine intake included iodine from both supplements and diet. Multiple outcome measures were used to evaluate possible adverse effects, including thyroid function, thyroid size, and urinary iodine. RESULTS: The mean iodine intake from the diets and salt intake of the participants were 105 ± 25 and 258 ± 101 µg/d, respectively. In comparison with the placebo group, all iodide-supplemented groups responded with significant increases in median urinary iodine concentrations (P < 0.05) and in thyroid-stimulating hormone concentration (P < 0.05). Thyroid volume decreased after 4 wk in the high-iodine intervention groups (1500-2000 µg). Subclinical hypothyroidism appeared in the groups that received 400 µg I (5%) and 500-2000 µg I (15-47%). CONCLUSIONS: This study showed that subclinical hypothyroidism appeared in the participants who took the 400-µg I supplement, which provided a total iodine intake of ∼800 µg/d. Thus, we caution against a total daily iodine intake that exceeds 800 µg/d in China and recommend further research to determine a safe daily upper limit.


Assuntos
Suplementos Nutricionais/efeitos adversos , Hipotireoidismo/induzido quimicamente , Iodo/efeitos adversos , Glândula Tireoide/efeitos dos fármacos , Tireotropina/sangue , Oligoelementos/efeitos adversos , Adulto , China/epidemiologia , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/epidemiologia , Incidência , Iodetos/administração & dosagem , Iodetos/efeitos adversos , Iodo/administração & dosagem , Iodo/urina , Masculino , Tamanho do Órgão , Valores de Referência , Cloreto de Sódio na Dieta/administração & dosagem , Glândula Tireoide/anatomia & histologia , Oligoelementos/administração & dosagem , Oligoelementos/urina , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA