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1.
Front Med (Lausanne) ; 10: 1133585, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37234245

RESUMO

Objective: To determine the comparative effects of acupuncture and related techniques-assisted general anesthesia (GA) on the total dosage of main anesthetic drugs administered during surgery. Methods: The following data bases were searched on June 30, 2022: Embase, Cochrane, PubMed, Web of Science, CBM, CNKI, WANFANG and VIP to find randomized controlled trials (RCTs). A random-effects Bayesian network meta-analysis and subgroup analysis were employed. The GRADE system was applied to make evidence quality assessments. The intraoperative total doses of propofol and remifentanil were the primary and secondary outcomes, respectively. The weighted mean difference (WMD) with 95% confidence intervals (CI) were determined to measure the size of any potential effect. Results: Seventy-six RCTs that involved 5,877 patients were included in the analysis. Compared with GA, a significant decrease in the total dose of propofol was found for manual acupuncture (MA) assisted GA (WMD = -101.26 mg, 95% CI [-172.98, -27.06]) with moderate quality, electroacupuncture (EA) assisted GA (WMD = -54.25 mg, 95% CI [-87.25, -22.37]) with moderate quality and transcutaneous electrical acupoint stimulation (TEAS) assisted GA (WMD = -39.99 mg, 95% CI [-57.96, -22.73]) with moderate quality, respectively. A significant reduction in the total dose of remifentanil was found in favor of EA-assisted GA (WMD = -372.33 µg, 95% CI [-558.44, -196.43]) with low quality and TEAS-assisted GA (WMD = -215.77 µg, 95% CI [-305.23, -128.04]) with low quality. According to the surface under cumulative ranking area (SUCRA), MA-assisted GA and EA-assisted GA ranked first in the reduction of the total dosage of propofol and remifentanil administered, with a probability of 0.85 and 0.87, respectively. Conclusions: Both EA- and TEAS-assisted GA significantly reduced the intraoperative total dosage of propofol and remifentanil administered. EA produced the greatest reduction in these two outcomes compared to TEAS. Although all the comparisons are low to moderate based on GRADE evidence, EA seems to be an advisable acupuncture technique to reduce the dosage of anesthetic drugs required in surgical patients under GA.

2.
Arch Oral Biol ; 150: 105691, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37043987

RESUMO

OBJECTIVE: To study the effect of EGCG on tooth movement and root resorption during orthodontic treatment in rats. METHODS: A total of thirty six male Wistar rats were randomly and equally divided into three groups: control, 50 mg/kg EGCG, and 100 mg/kg EGCG. During the experiment, the subjects were submitted to an orthodontic tooth movement (OTM) model, rats in the experimental groups were given the corresponding dose of EGCG, while rats in the control group were administrated with an equal volume of normal saline solution by gavage. After 14 days of OTM, the rats were sacrificed by transcardial perfusion. Micro-CT of rat maxillaes was taken to analyze OTM distance and root resorption. The maxillary samples were prepared as histological sections for H&E staining, tartrate-resistant acid phosphatase (TRAP) staining and immunohistochemical (IHC) staining to be observed and analyzed. RESULTS: The OTM distance and root resorption of rats in the dosed group decreased, and the number of TRAP positive cells in their periodontium decreased significantly. The expression level of RANKL was decreased in the EGCG group compared to the control group, while that of OPG, OCN and Runx2 was increased. Effects were more pronounced in 100 mg/kg group than in 50 mg/kg group. CONCLUSION: EGCG reduces OTM and orthodontic induced root resorption (OIRR) in rats, and is able to attenuate osteoclastogenesis on the pressure side and promote osteogenesis on the tension side.


Assuntos
Reabsorção da Raiz , Ratos , Masculino , Animais , Reabsorção da Raiz/tratamento farmacológico , Ratos Wistar , Osteoclastos , Técnicas de Movimentação Dentária , Chá , Raiz Dentária
3.
Int J Biol Macromol ; 237: 123932, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36894058

RESUMO

In this study, the coaxial nanofiber films were prepared by coaxial electrospinning technique with cinnamaldehyde (CMA) and tea polyphenol (TP) as core material and polylactic acid (PLA) as shell material, and to obtain food packaging materials with great physicochemical and antibacterial properties, zinc oxide (ZnO) sol were added into PLA, and ZnO/CMA/TP-PLA coaxial nanofiber films were prepared. Meanwhile, the microstructure and physicochemical properties were determined, and the antibacterial properties and mechanism were investigated with Shewanella putrefaciens (S. putrefaciens) as target. The results show that the ZnO sol makes the physicochemical properties and antibacterial properties of the coaxial nanofiber films improve. Among them, the 1.0 % ZnO/CMA/TP-PLA coaxial nanofibers have smooth and continuous uniform surfaces, and their encapsulation effect on CMA/TP and antibacterial properties are the optimal. The synergistic action of CMA/TP and ZnO sol cause severe depression and folding of the cell membrane of S. putrefaciens, makes cell membrane permeability increase and of intracellular materials spillage, interference the bacteriophage protein expression, and makes macromolecular protein degraded. In this study, the introduction of oxide sols into polymeric shell materials by in-situ synthesis technique can provide theoretical support and methodological guidance for the application of electrospinning technology in the field of food packaging.


Assuntos
Nanofibras , Shewanella putrefaciens , Óxido de Zinco , Nanofibras/química , Óxido de Zinco/química , Polifenóis , Poliésteres/química , Antibacterianos/química , Chá
4.
J Control Release ; 353: 337-349, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36462641

RESUMO

Successfully treating bone infections is a major orthopedic challenge. Clinically, oral, intravenous, or intramuscular injections of drugs are usually used for direct or complementary treatment. However, once the drug enters the system, it circulates throughout the body, leading to an insufficient local dose and limiting the therapeutic effect because of the lack of targeting in the drug system. In this study, ß-cyclodextrin, modified with poly (ethylene glycol) [PEG] and aspartic acid hexapeptide (Asp6-ß-CD), was used to specifically target the hydroxyapatite (HA) component of the bone. It was then loaded with norfloxacin (NFX) to treat bone infections. The antibacterial ability of NFX was enhanced by loading it into Asp6-ß-CD, because the solubility of Asp6-ß-CD@NFX increased significantly. Moreover, Asp6-ß-CD could target bone tissue in nude mice and showed significantly enhanced accumulation (10 times) than the unmodified ß-CD. In addition, in a rat model of osteomyelitis, Asp6-ß-CD@NFX targeted HA well and exerted its antibacterial activity, which reduced inflammation and promoted bone tissue repair. This study indicates that the Asp6-ß-CD based drug delivery system can efficiently target bone tissue to enable potential applications for treating bone-related diseases.


Assuntos
Osteomielite , beta-Ciclodextrinas , Camundongos , Ratos , Animais , Camundongos Nus , Sistemas de Liberação de Medicamentos , Antibacterianos/uso terapêutico , Polietilenoglicóis , Preparações Farmacêuticas , Durapatita , Osteomielite/tratamento farmacológico
5.
Front Immunol ; 13: 1009530, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389762

RESUMO

Tetrastigma hemsleyanum Diels et Gilg is a traditional Chinese herbal medicine with high medicinal value, and antitumor, antioxidant and anti-inflammatory biological activities. However, while several studies have focused on flavonoids in Tetrastigma hemsleyanum tubers, there are few studies on the enhanced immune effect of Tetrastigma hemsleyanum polysaccharides (THP). In this study, we evaluated the antitumor effect of THP in a lung tumor model and explored the mechanism of antitumor activity through intestinal flora. In addition, a cyclophosphamide (CTX)-induced immunosuppression model was used to declare the immunomodulatory effect of THP in the immunosuppressive state induced by antitumor drugs. The results showed that THP increased the content of ileum secreted immunoglobulin A (SIgA) and cecum short-chain fatty acids (SCFAs) and improved microbial community diversity, regulating the relative abundance of dominant microbiota flora from the phylum level to the genus level, and recovering the intestinal microflora disorder caused by tumors. Additionally, THP can increase the organ indices and improve immune organ atrophy. THP can upregulate routine blood counts and stimulate the production of the serum cytokines. THP also promoted the macrophage phagocytic index, NK-cell activation, and complement and immunoglobulin (IgG, IgA, IgM) levels. The detection of Splenic lymphocyte proliferation and T lymphocyte subsets also sideways reflects that THP can restore CTX-induced immune inhibition in mice. In conclusion, this study suggests that THP can effectively achieve the enhanced antitumor effects, regulate gut microbiota and improve the immunosuppression induced by antitumor drugs. Therefore, THP can enhance the immune capacity and provide novel immunomodulatory and antineoplastic adjuvant agents.


Assuntos
Microbioma Gastrointestinal , Vitaceae , Camundongos , Animais , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Imunidade , Imunomodulação
6.
ACS Sens ; 7(9): 2759-2766, 2022 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-36041054

RESUMO

The multiplexed digital polymerase chain reaction (PCR) is widely used in molecular diagnosis owing to its high sensitivity and throughput for multiple target detection compared with the single-plexed digital PCR; however, current multiplexed digital PCR technologies lack efficient coding strategies that do not compromise the sensitivity and signal-to-noise (S/N) ratio. Hence, we propose a fluorescent-encoded bead-based multiplexed droplet digital PCR method for ultra-high coding capacity, along with the creative design of universal sequences (primer and fluorescent TaqMan probe) for ultra-sensitivity and high S/N ratios. First, pre-amplification is used to introduce universal primers and universal fluorescent TaqMan probes to reduce primer interference and background noise, as well as to enrich regions of interest in targeted analytes. Second, fluorescent-encoded beads (FEBs), coupled with the corresponding target sequence-specific capture probes through streptavidin-biotin conjugation, are used to partition amplicons via hybridization according to the Poisson distribution. Finally, FEBs mixed with digital PCR mixes are isolated into droplets generated via Sapphire chips (Naica Crystal Digital PCR system) to complete the digital PCR and result analysis. For proof of concept, we demonstrate that this method achieves high S/N ratios in a 5-plexed assay for influenza viruses and SARS-CoV-2 at concentrations below 10 copies and even close to a single molecule per reaction without cross-reaction, further verifying the possibility of clinical actual sample detection with 100% accuracy, which paves the way for the realization of digital PCR with ultrahigh coding capacity and ultra-sensitivity.


Assuntos
Biotina , COVID-19 , Óxido de Alumínio , Teste para COVID-19 , Corantes Fluorescentes/química , Humanos , Reação em Cadeia da Polimerase Multiplex/métodos , SARS-CoV-2/genética , Estreptavidina/química
7.
Comput Biol Med ; 145: 105448, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35364310

RESUMO

BACKGROUND: Inflammation is the pathogenesis of various chronic diseases plaguing clinic for years.Fallopia multiflora (Thunb.) is a traditional Chinese herbal medicine with a long history of application in detoxification and anti-inflammation. 2,3,4',5-Tetrahydroxystilbene 2-o-D-glucoside (TSG) is a main active compound of F. multiflora. However, the mechanism of TSG in the treatment of inflammation remains unknown. METHODS: Network pharmacology and molecular docking were employed to explore the mechanism of anti-inflammatory effect of TSG. Potential targets of TSG and inflammation were obtained from Swiss Target Prediction, Pharm Mapper, and GeneCards database. Protein-protein interaction (PPI) networks, GO and KEGG pathway enrichment analysis were performed to elucidate the interaction of targets. Moreover, the anti-inflammatory effect of TSG was validated by in vitro experiments using flow cytometry, RT-qPCR, Western blot, and immunocytochemistry assays. RESULTS: PPI network and gene enrichment analysis showed that TSG may exert a protein kinase binding activity, and IKBKB, MAPK1, NFKBIA, and RELA were predicted as the targets of anti-inflammation. Verified by molecular docking and Western blot, TSG may target NF-κB and ERK2 related signals to alleviate inflammatory damage. Furthermore, TSG effectively downregulated the expression of inflammatory cytokine, the nuclear translocation of NF-κB p65, and the production of reactive oxygen species (ROS). CONCLUSION: TSG possesses significant anti-inflammatory effect. TSG may display a protein kinase binding activity and target NF-κB and ERK2 related signals to treat the inflammation. This work may enlighten the potential application of TSG in anti-inflammation and indicate network pharmacology was an effective tool for the further study of TCM.


Assuntos
Medicamentos de Ervas Chinesas , NF-kappa B , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Farmacologia em Rede , Proteínas Quinases/uso terapêutico
8.
Pharmacol Res ; 179: 106203, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35381342

RESUMO

More than 100 species of annual herb genus Suaeda widely distribute (Asia, North America, northern Africa and Europe), are rich in resources (about hundreds of millions of tons/Y) and have a long historical application. Most of them are mainly used for traditional food, feed and medicine. Recently, they have been employed to repair saline-alkali land and beautify the environment. So far, only 27 species have been reported on the bioactivity diversity, broad spectrum and effectiveness in clinical practice. Therefore, the in-depth and extensive research of Suaeda has become a research hotspot around the world. However, only one review summarized the nutritional, chemical and biological values of Suaeda. By searching the international authoritative databases (ACS Publications, ScienceDirect, PubMed, Springer, web of Science and Bing International etc.) and collecting 103 literatures closely related to Suaeda (1895-2021), herewith a comprehensive and systematic review was conducted on the phytology, chemistry, pharmacology and clinical application, enveloping the classification evolution between Amaranthaceae and Chenopodiaceae, distribution and common botanical characteristics; involving 9 chemical categories of 163 derivatives covering 14 new and 6 first-isolated ones, and appraising the content determination of 6 categories of components; mainly including the pharmacology of 13 species in vivo and vitro; estimating the clinical application of 16 species cured the related diseases of eight human physiological system except for the motor system. It is expected that this paper will provide forward-looking scientific ideas and literature support for the further modern research, development and utilization of the genus.


Assuntos
Chenopodiaceae , Fitoterapia , Etnofarmacologia , Europa (Continente) , Humanos , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia
9.
Phytomedicine ; 96: 153860, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34836743

RESUMO

BACKGROUND: The inflammatory state of diabetes promotes high platelet response and endothelial adhesion, which are the main risk factors for cardiovascular events. Tetramethylpyrazine (TMP) is an amide alkaloid isolated from the traditional Chinese medicine Rhizoma Ligustici Chuanxiong, which has been widely used in the clinical treatment of ischemic cardiovascular disease. PURPOSE: This study aimed to investigate whether TMP could alleviate diabetes-induced high platelet response and endothelial adhesion and the underlying mechanisms. METHODS: Type 2 diabetes mellitus (T2DM) rat model was established by high-fat feeding combined with low dose of streptozotocin. Rats in the TMP treatment group were administered with TMP (100 or 200 mg/kg) for 21 days. Cultured human umbilical vein endothelial cells (HUVECs) were stimulated with glucose (5.5 mM) to induce endothelial activation. The NOD-like receptor protein 3 (NLRP3) over- and low-expressing cell models were established via transfection of NLRP3 lentivirus plasmid into HUVECs. INF39 (25 mg/kg), a chemical inhibitor of NLRP3 inflammasome, was used to explore the role of NLRP3 in T2DM associated high platelet response and endothelial adhesion. RESULTS: TMP effectively improved the prothrombotic phenotypes and inhibited the expression of vascular inflammatory factors and adhesion molecules in T2DM rats. TMP inhibited NLRP3 inflammasome and reduced the adhesion of HUVECs to platelets and monocytes in vitro. Over-expression of NLRP3 blocked the effect of TMP on HUVECs activation and adhesion, while TMP had no effect on NLRP3 low-expressing HUVECs. The NLRP3 inhibitor INF39 produced similar effects of TMP on diabetes-induced high platelet response, endothelial adhesion and vascular inflammation. CONCLUSION: TMP ameliorates diabetes-induced high platelet response and endothelial adhesion via inhibiting NLRP3 inflammasome activation in T2DM rats, which provide a new basis for the clinical prevention and treatment of diabetes-associated cardiovascular events.


Assuntos
Diabetes Mellitus Tipo 2 , Inflamassomos , Animais , Plaquetas , Diabetes Mellitus Tipo 2/tratamento farmacológico , Células Endoteliais da Veia Umbilical Humana , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteínas NLR , Pirazinas , Ratos
10.
Int J Biol Macromol ; 184: 739-749, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34174310

RESUMO

Polylactic acid (PLA) is a promising food packaging material with biocompatible, nontoxic and biodegradable. In order to reduce the deterioration of aquatic products caused by microorganisms, PLA coaxial nanofiber films with cinnamaldehyde (CMA), tea polyphenol (TP) and its composite as core materials were prepared by using coaxial electrospinning technology. Its microscopic morphology and structure were characterized separately, and its thermal stability, wettability and mechanical properties were determined. The antibacterial activity and antibacterial mechanism of nanofiber films were studied with Shewanella putrefaciens (S. putrefaciens) which is the dominant spoilage of aquatic products as the target of action. The results show that the CMA/TP (m/m = 2:5)-PLA coaxial nanofibers have small diameter, uniform distribution, smooth surface, no pores and fracture. At the same time, the film has strong hydrophobicity, good thermal stability and mechanical properties. Its antibacterial performance is better than that of single-core nanofiber films, which effectively destroys the cell membrane of S. putrefaciens, increases the permeability of cell membrane, and interferes with the synthesis and expression of its protein. The coaxial nanofiber films with CMA, TP and its composite as core material can be used as a fresh-keeping material with antibacterial properties, and has potential application value in the field of food preservation.


Assuntos
Acroleína/análogos & derivados , Antibacterianos/síntese química , Poliésteres/química , Polifenóis/síntese química , Shewanella putrefaciens/efeitos dos fármacos , Chá/química , Acroleína/química , Antibacterianos/química , Antibacterianos/farmacologia , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Estabilidade de Medicamentos , Microbiologia de Alimentos , Embalagem de Alimentos , Temperatura Alta , Interações Hidrofóbicas e Hidrofílicas , Nanofibras , Polifenóis/química , Polifenóis/farmacologia
11.
Phytother Res ; 35(7): 3916-3935, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33970512

RESUMO

The programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is abnormally expressed in cervical cancer cells. Moreover, PD-1/PD-L1 blockade reduces the apoptosis and exhaustion of T cells and inhibits the development of malignant tumors. Usnic acid is a dibenzofuran compound originating from Usnea diffracta Vain and has anti-inflammatory, antifungal, and anticancer activities. However, the molecular mechanism of its antitumor effects has not been fully elucidated. In this work, we first observed that usnic acid decreased the expression of PD-L1 in HeLa cells and enhanced the cytotoxicity of co-cultured T cells toward tumor cells. Usnic acid inhibited PD-L1 protein synthesis by reducing STAT3 and RAS pathways cooperatively. It was subsequently shown that usnic acid induced MiT/TFE nuclear translocation through the suppression of mTOR signaling pathways, and promoted the biogenesis of lysosomes and the translocation of PD-L1 to the lysosomes for proteolysis. Furthermore, usnic acid inhibited cell proliferation, angiogenesis, migration, and invasion, respectively, by downregulating PD-L1, thereby inhibiting tumor growth. Taken together, our results show that usnic acid is an effective inhibitor of PD-L1 and our study provide novel insights into the mechanism of its anticancer targeted therapy.


Assuntos
Antígeno B7-H1 , Benzofuranos/farmacologia , Proliferação de Células/efeitos dos fármacos , Linfócitos T/imunologia , Antígeno B7-H1/antagonistas & inibidores , Linhagem Celular Tumoral , Células HeLa , Humanos , Parmeliaceae/química
12.
Brain Lang ; 215: 104920, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33561785

RESUMO

Acupuncture, taking the advantage of modality-specific neural pathways, has shown promising results in the treatment of brain disorders that affect different modalities such as pain and vision. However, the precise underlying mechanisms of within-modality neuromodulation of acupoints on human high-order cognition remain largely unknown. In the present study, we used a non-invasive and easy-operating method, focused ultrasound, to stimulate two language-relevant acupoints, namely GB39 (Xuanzhong) and SJ8 (Sanyangluo), of thirty healthy adults. The effect of focused ultrasound stimulation (FUS) on brain activation was examined by functional magnetic resonance imaging (fMRI). We found that stimulating GB39 and SJ8 by FUS evoked overlapping but distinct brain activation patterns. Our findings provide a major step toward within-modality (in this case, language) acupoint-brain (acubrain) mapping and shed light on to the potential use of FUS as a personalized treatment option for brain disorders that affect high-level cognitive functions.


Assuntos
Pontos de Acupuntura , Idioma , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética
13.
Cell Commun Signal ; 19(1): 24, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627137

RESUMO

BACKGROUND: The oncogenic transcript factor c-Maf is stabilized by the deubiquitinase Otub1 and promotes myeloma cell proliferation and confers to chemoresistance. Inhibition of the Otub1/c-Maf axis is a promising therapeutic target, but there are no inhibitors reported on this specific axis. METHODS: A luciferase assay was applied to screen potential inhibitors of Otub1/c-Maf. Annexin V staining/flow cytometry was applied to evaluate cell apoptosis. Immunoprecipitation was applied to examine protein ubiquitination and interaction. Xenograft models in nude mice were used to evaluate anti-myeloma activity of AVT. RESULTS: Acevaltrate (AVT), isolated from Valeriana glechomifolia, was identified based on a bioactive screen against the Otub1/c-Maf/luciferase system. AVT disrupts the interaction of Otub1/c-Maf thus inhibiting Otub1 activity and leading to c-Maf polyubiquitination and subsequent degradation in proteasomes. Consistently, AVT inhibits c-Maf transcriptional activity and downregulates the expression of its target genes key for myeloma growth and survival. Moreover, AVT displays potent anti-myeloma activity by triggering myeloma cell apoptosis in vitro and impairing myeloma xenograft growth in vivo but presents no marked toxicity. CONCLUSIONS: The natural product AVT inhibits the Otub1/c-Maf axis and displays potent anti-myeloma activity. Given its great safety and efficacy, AVT could be further developed for MM treatment. Video Abstract.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Cisteína Endopeptidases/metabolismo , Inibidores de Cisteína Proteinase/uso terapêutico , Iridoides/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Proteínas Proto-Oncogênicas c-maf/antagonistas & inibidores , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cisteína Endopeptidases/genética , Inibidores de Cisteína Proteinase/farmacologia , Feminino , Humanos , Iridoides/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Proteínas Proto-Oncogênicas c-maf/genética , Proteínas Proto-Oncogênicas c-maf/metabolismo
14.
Int J Nanomedicine ; 15: 5629-5643, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801706

RESUMO

PURPOSE: Lecithin/chitosan nanoparticles have shown great promise in the transdermal delivery of therapeutic agents. Baicalein, a natural bioactive flavonoid, possesses multiple biological activities against dermatosis. However, its topical application is limited due to its inherently poor hydrophilicity and lipophilicity. In this study, the baicalein-phospholipid complex was prepared to enhance the lipophilicity of baicalein and then lecithin/chitosan nanoparticles loaded with the baicalein-phospholipid complex were developed to improve the transdermal retention and permeability of baicalein. METHODS: Lecithin/chitosan nanoparticles were prepared by the solvent-injection method and characterized in terms of particle size distribution, zeta potential, and morphology. The in vitro release, the ex vivo and in vivo permeation studies, and safety evaluation of lecithin/chitosan nanoparticles were performed to evaluate the effectiveness in enhancing transdermal retention and permeability of baicalein. RESULTS: The lecithin/chitosan nanoparticles obtained by the self-assembled interaction of chitosan and lecithin not only efficiently encapsulated the drug with high entrapment efficiency (84.5%) but also provided sustained release of baicalein without initial burst release. Importantly, analysis of the permeation profile ex vivo and in vivo demonstrated that lecithin/chitosan nanoparticles prolonged the retention of baicalein in the skin and efficiently penetrated the barrier of stratum corneum without displaying skin irritation. CONCLUSION: These results indicate the potential of drug-phospholipid complexes in enhancing the entrapment efficiency and self-assembled lecithin/chitosan nanoparticles based on phospholipid complexes in the design of a rational transdermal delivery platform to improve the efficiency of transdermal therapy by enhancing its percutaneous retention and penetration in the skin.


Assuntos
Flavanonas/administração & dosagem , Nanopartículas/administração & dosagem , Fosfolipídeos/química , Administração Cutânea , Animais , Quitosana/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Flavanonas/farmacocinética , Interações Hidrofóbicas e Hidrofílicas , Lecitinas/química , Masculino , Nanopartículas/efeitos adversos , Nanopartículas/química , Permeabilidade , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/patologia , Absorção Cutânea/efeitos dos fármacos , Testes de Irritação da Pele
15.
Chemosphere ; 246: 125794, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31918102

RESUMO

Environmental contamination by heavy metals, such as lead (Pb), can lead to severe immune dysfunction. MicroRNAs (miRNAs) are involved in regulating immunity. Whether Pb can regulate neutrophil apoptosis through miRNA, and whether selenium (Se) can antagonize this response are still unknown. We treated neutrophils with 12.5 µM (CH3OO)2Pb and 1 µM Na2SeO3 for 3 h, after which apoptosis was evaluated using acrideine orange/ethidium bromide (AO/EB) dual fluorescent staining and flow cytometry. The results showed that neutrophil apoptosis was significantly increased following Pb exposure, and that this response was prevented upon Se addition. Pb up-regulates miR-16-5p and leads to the subsequent down-regulation of the target genes phosphoinositide-3-kinase regulatory subunit 1 (PiK3R1), insulin-like growth factor 1 receptor (IGF1R), and phosphatidylinositol 3 kinase (Pi3K)-protein kinase B (AKT), followed by activation of the tumor protein P53 (P53)-B-cell lymphoma-2 (Bcl-2)/Bcl-2-Associated X protein (Bax)-cytochrome c (Cytc)-Caspase 9 (mitochondrial apoptotic pathway) and the tumor necrosis factor receptor superfamily member 6 (Fas)-Fas-associated death domain protein (Fadd)-Caspase 8 (death receptor pathway). Pb also triggered oxidative stress and indirectly activated the mitochondrial apoptotic pathway. We conclude that miR-16-5p plays a key role in the apoptosis of neutrophils exposed to Pb by down-regulating the expression of PiK3R1 and IGFR1, thereby activating the mitochondrial apoptotic pathway and death receptor pathway. Se can prevent Pb-induced apoptosis.


Assuntos
Poluentes Ambientais/toxicidade , Chumbo/toxicidade , MicroRNAs/metabolismo , Neutrófilos/efeitos dos fármacos , Fosfatidilinositol 3-Quinase/metabolismo , Substâncias Protetoras/metabolismo , Receptor IGF Tipo 1/metabolismo , Selênio/metabolismo , Animais , Apoptose/efeitos dos fármacos , Galinhas/metabolismo , Galinhas/fisiologia , Chumbo/metabolismo , MicroRNAs/genética , Mitocôndrias/metabolismo , Neutrófilos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Selênio/química , Proteína Supressora de Tumor p53
16.
Front Microbiol ; 10: 2584, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798551

RESUMO

The quorum sensing (QS) system controls bacterial biofilm formation, which is highly related to the virulence and resistance of pathogens. In the present study, the effect of two traditional Chinese medicine (TCM) monomers, berberine and matrine, on biofilm formation and QS-related gene expression of antimicrobial-resistant (AMR) Escherichia coli strains was investigated by laser scanning confocal microscopy (LSCM) observation and real-time PCR. The results indicated a roughly positive relationship between biofilm formation ability and antimicrobial resistance. LSCM observation showed that berberine and matrine inhibited biofilm formation of AMR E. coli strains at 1/2 minimal inhibitory concentration (MIC) (1/2 MIC berberine at OD630: 0.1020; 1/2 MIC matrine: OD630: 0.1045); furthermore, abnormal cell morphology such as rounded and elongated cells was also observed. This finding was consistent with the downregulation of QS-related genes: luxS, pfS, sdiA, hflX, motA, and fliA. At 1/2 MIC and 1/4 MIC concentrations of berberine, a significant downregulation of luxS, pfS, hflX, ftsQ, and ftsE was observed. The results indicate that berberine and matrine can inhibit biofilm formation by inhibiting the QS system and that berberine is more effective than matrine.

17.
Cancer Epidemiol Biomarkers Prev ; 25(7): 1050-1058, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27197287

RESUMO

BACKGROUND: Epidemiologic studies and secondary analyses of randomized trials supported the hypothesis that selenium and vitamin E lower prostate cancer risk. However, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed no benefit of either supplement. Genetic variants involved in selenium or vitamin E metabolism or transport may underlie the complex associations of selenium and vitamin E. METHODS: We undertook a case-cohort study of SELECT participants randomized to placebo, selenium, or vitamin E. The subcohort included 1,434 men; our primary outcome was high-grade prostate cancer (N = 278 cases, Gleason 7 or higher cancer). We used weighted Cox regression to examine the association between SNPs and high-grade prostate cancer risk. To assess effect modification, we created interaction terms between randomization arm and genotype and calculated log likelihood statistics. RESULTS: We noted statistically significant (P < 0.05) interactions between selenium assignment, SNPs in CAT, SOD2, PRDX6, SOD3, and TXNRD2, and high-grade prostate cancer risk. Statistically significant SNPs that modified the association of vitamin E assignment and high-grade prostate cancer included SEC14L2, SOD1, and TTPA In the placebo arm, several SNPs, hypothesized to interact with supplement assignment and risk of high-grade prostate cancer, were also directly associated with outcome. CONCLUSION: Variants in selenium and vitamin E metabolism/transport genes may influence risk of overall and high-grade prostate cancer, and may modify an individual man's response to vitamin E or selenium supplementation with regards to these risks. IMPACT: The effect of selenium or vitamin E supplementation on high-grade prostate cancer risk may vary by genotype. Cancer Epidemiol Biomarkers Prev; 25(7); 1050-8. ©2016 AACR.


Assuntos
Biomarcadores Tumorais/sangue , Variação Genética , Neoplasias da Próstata/genética , Selênio/metabolismo , Vitamina E/metabolismo , Idoso , Transporte Biológico/genética , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Modelos de Riscos Proporcionais , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Fatores de Risco , Vitamina E/genética
18.
Prostate ; 76(7): 691-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26847995

RESUMO

BACKGROUND: Genetic variations in some of the selenoprotein genes, alone or together with an individual's selenium status, may influence risk or progression of prostate cancer. We investigated the impact of genetic variants of selenoproteins on plasma selenium levels and cancer aggressiveness at diagnosis in men with localized prostate cancer (PCa). METHODS: The study cohort comprised 722 patients seen at Dana-Farber Cancer Institute who had localized/locally advanced PCa (i.e., stage T3 or less, N0, and M0) from 1994 to 2001. Fifty-five tagging single nucleotide polymorphisms (SNPs) from six selenoprotein genes (TXNRD1, TXNRD2, SEP15, GPX3, SELENBP1, and SEPP1) were analyzed. Logistic regression is used to examine associations of genotypes and plasma selenium levels with risk of aggressive disease, defined as D'Amico intermediate/high risk categories. Step down permutation was applied to adjust for multiple comparisons. RESULTS: Three hundred and forty-eight patients (48%) had aggressive disease at diagnosis. Two SNPs were associated with cancer aggressiveness at diagnosis (unadjusted P = 0.017 and 0.018, respectively). The odds ratio for aggressive disease in patients carrying TXNRD2 rs1005873-AG/GG genotypes or SELENBP1 rs10788804-AG/AA genotypes was 1.54 (95% CI = 1.08, 2.20) and 1.45 (95% CI = 1.07, 1.98), respectively, compared to TXNRD2 rs1005873-AA or SELENBP1 rs10788804-GG carriers. Four SNPs in TXNRD2 (rs1005873, rs13054371, rs3788310, and rs9606174) and the rs230820 in SEPP1 were associated with plasma selenium levels (unadjusted P < 0.05). Permutation adjusted P-values were not statistically significant for all these comparisons at the cut-off point of 0.05. CONCLUSION: We identified polymorphisms in selenoproteins that may influence the plasma selenium levels and may be associated with the risk of presenting with aggressive PCa in men with localized or locally advanced PCa. These results should be validated in other independent datasets.


Assuntos
Predisposição Genética para Doença , Invasividade Neoplásica/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Selênio/sangue , Estudos de Casos e Controles , Estudos de Associação Genética , Genótipo , Glutationa Peroxidase/genética , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Proteínas de Ligação a Selênio/genética , Selenoproteínas/genética , Tiorredoxina Redutase 1/genética , Tiorredoxina Redutase 2/genética
19.
Zhongguo Zhong Yao Za Zhi ; 41(4): 630-635, 2016 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-28871684

RESUMO

The skin transcriptome of Bufu bufo gargarizans was determined by conventional methods. A novel full length cDNA coding for a Cathelicidin precursor was identified by transcriptomic data assembling, annotation and blast search of corresponding data banks. According to the known processing methods of Cathelicidin family members, present reported novel Cathelicidin precursor of B. bufo gargarizans might be cleaved at 2 possible sites of the same precursor and generate both BG-CATH25 and BG-CATH29 as mature molecules. The deduced BG-CATH25 and BG-CATH29 were synthesized with purity>95% to evaluate the properties and bactericidal activities. The secondary structural characteristics of both BG-CATH25 and BG-CATH29 in different solutions were determined by Circular Dichroism (CD) Analysis. CD results indicated that random coil conformation were the main structural elements for both BG-CATH25 and BG-CATH29 in different buffer systems. Antimicrobial activities against tested bacterial strains were carried out by plating method. Both BG-CATH25 and BG-CATH29 showed strong antibacterial activities against Aeromonas hydrophila, with MIC values of 1.25, 10 mg•L⁻¹, respectively. However, both of them showed weak bactericidal activities against human pathogenic bacteria, like Escherichia coli (ATCC25922),Staphylococcus aureus (ATCC25923)and Pseudomonas aeruginosa (ATCC 27853).


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Bufonidae/metabolismo , Pele/metabolismo , Animais , Antibacterianos/metabolismo , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/metabolismo , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bufonidae/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pele/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Catelicidinas
20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(11): 3671-5, 2016 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-30226685

RESUMO

LIBS (laser-induced breakdown spectroscopy) was used to detect Fe element content in soybean oil quantitatively. In this experiment, a series of soybean oil samples with different concentrations of Fe were used; LIBS spectra were collected with a two-channel high precision spectrometer. According to the LIBS spectrum of samples, two characteristic wavelength of Fe (404.58 and 406.36 nm) were determined, and different simple regression methods (exponential regression, linear regression and quadratic regression) were used to establish the quantitative analysis models of Fe content using each characteristic spectral line. The results indicate that the average relative error of Fe I 404.58 and Fe I 406.36 in simple exponential regression, linear regression and quadratic regression models were 29.49%, 8.93%, 8.70% and 28.95%, 8.63%, 8.44%, respectively. The results of Fe I 406.36 regression models is better than that of Fe I 404.58, and the quadratic regression model is optimal among the three regression models. According to these results, LIBS technology has certain feasibility for detecting Fe in soybean oil; the quadratic linear regression model can improve the prediction accuracy of Fe element effectively.


Assuntos
Ferro/análise , Lasers , Análise de Regressão , Óleo de Soja , Análise Espectral
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