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The study of tumor nanovaccines (NVs) has gained interest because they specifically recognize and eliminate tumor cells. However, the poor recognition and internalization by dendritic cells (DCs) and insufficient immunogenicity restricted the vaccine efficacy. Herein, we extracted two molecular-weight Astragalus polysaccharides (APS, 12.19 kD; APSHMw, 135.67 kD) from Radix Astragali and made them self-assemble with OVA257-264 directly forming OVA/APS integrated nanocomplexes through the microfluidic method. The nanocomplexes were wrapped with a sheddable calcium phosphate layer to improve stability. APS in the formed nanocomplexes served as drug carriers and immune adjuvants for potent tumor immunotherapy. The optimal APS-NVs were approximately 160 nm with uniform size distribution and could remain stable in physiological saline solution. The FITC-OVA in APS-NVs could be effectively taken up by DCs, and APS-NVs could stimulate the maturation of DCs, improving the antigen cross-presentation efficiency in vitro. The possible mechanism was that APS can induce DC activation via multiple receptors such as dectin-1 and Toll-like receptors 2 and 4. Enhanced accumulation of APS-NVs both in draining and distal lymph nodes were observed following s.c. injection. Smaller APS-NVs could easily access the lymph nodes. Furthermore, APS-NVs could markedly promote antigen delivery efficiency to DCs and activate cytotoxic T cells. In addition, APS-NVs achieve a better antitumor effect in established B16-OVA melanoma tumors compared with the OVA+Alum treatment group. The antitumor mechanism correlated with the increase in cytotoxic T cells in the tumor region. Subsequently, the poor tumor inhibitory effect of APS-NVs on the nude mouse model of melanoma also confirmed the participation of antitumor adaptive immune response induced by NVs. Therefore, this study developed a promising APS-based tumor NV that is an efficient tumor immunotherapy without systemic side effects.
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Vacinas Anticâncer , Melanoma , Camundongos , Animais , Nanovacinas , Melanoma/patologia , Células Dendríticas , Adjuvantes Imunológicos/farmacologia , Imunoterapia , Antígenos , Polissacarídeos/química , Camundongos Endogâmicos C57BLRESUMO
OBJECTIVE: To explore the mechanism of modified Huanglian Maidong decoction (Maidong-Sanqi-Huanglian Compounds, MSHCs) intervention in type 2 diabetes mellitus (T2DM). METHOD: This study used PubChem and SciFinder to collect the molecular structure of MSHCs, used PharmMapper to predict the potential targets of MSHC, and combined them with the T2DM gene to construct MSHC-T2DM protein-protein interaction (PPI) network. The plugin MCODE in Cytoscape 3.7.1 was then used to perform cluster analysis on the MSHC-T2DM PPI network. The genes and targets were input into DAVID for Gene Ontology (GO) and pathway enrichment analysis. Finally, animal experiments were performed to verify the therapeutic effect of MSHC on T2DM. RESULTS: Several T2DM-related targets, clusters, signaling pathways, and biological processes are found. The experimental results showed that compared with the blank group, the content of fasting blood glucose (FBG) in the model group was higher (P < 0.01). Compared with the model group, the content of FBG decreased and the insulin level increased in the MSHC medium-dose (0.15 g/kg) and high-dose (0.45 g/kg) groups and metformin group after 4 weeks of drug administration (P < 0.05). MSHC can also improve blood liquid levels and inflammatory factor levels (P < 0.05). CONCLUSION: MSHC may achieve therapeutic effects through regulating the T2DM-related targets, biological processes, and pathways, such as insulin resistance, energy metabolism, oxidative stress, and inflammation, found in this research.
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OBJECTIVE: To explore the protective mechanisms of the Traditional Chinese Medicine Bushenhuoxue (BSHX) in a rat model of vascular dementia (VD). METHODS: A rat model of VD was developed using bilateral common carotid artery occlusion (BCCAO). Rats were administered BSHX (10.14 or 5.07 g/kg), nimodipine (11.06 mg/kg; positive control), or saline (control) by gavage daily for 30 d post-surgery. Learning and memory abilities were assessed using the Morris water maze. Morphological changes in the hippocampus were observed using light microscopy (hematoxylin and eosin staining) and transmission electron microscopy (TEM). The mRNA and protein expression levels of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), phosphatidyl inositol 3-kinase (PI3K), serine/threonine kinase (AKT), and cAMP response element binding protein (CREB) were measured by real-time polymerase chain reaction (RT-PCR) and Western blot, respectively. RESULTS: Compared with the sham group, rats with BCCAO exhibited impaired learning and memory abilities (Morris water maze) and showed abnormalities in neuronal morphology (light microscopy) and ultrastructure (TEM) in the hippocampus. They also had decreased mRNA and protein expressions of BDNF, TrkB, PI3K, AKT, and CREB in hippocampal tissue (all P < 0.05). In rats with BCCAO, administration of BSHX attenuated deficits in learning and memory, improved the morphology and ultrastructure of hippocampal neurons, and enhanced mRNA and protein expression levels of BDNF, TrkB, PI3K, AKT, and CREB (all P < 0.05). CONCLUSION: BSHX may protect hippocampal neurons and improve learning and memory abilities, at least in part via the activation of BDNF/TrkB/PI3K/AKT/CREB signaling.
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Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cognição/efeitos dos fármacos , Demência Vascular/patologia , Demência Vascular/fisiopatologia , Transdução de Sinais/efeitos dos fármacos , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Demência Vascular/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/fisiopatologia , Masculino , Memória/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor trkB/metabolismo , Aprendizagem Espacial/efeitos dos fármacosRESUMO
OBJECTIVE: To compare the clinical effect on the joint attention and social communication in children with autism spectrum disorder (ASD) between the combined treatment of acupoint catgut embedding therapy with rehabilitation training and the simple application of rehabilitation training. METHODS: A total of 60 children with ASD were randomized into an observation group and a control group, 30 cases in each one. In the control group, the routine ASD rehabilitation training was adopted, including conductive education, speech training and music therapy, once a day. In the observation group, on the base of the treatment as the control group, the catgut embedding therapy was applied to Shenting (GV 24), Baihui (GV 20), Shenmen (HT 7) and the optic area (the point of scalp acupuncture), once a week. In the two groups, the treatment for 4 weeks was as one course, at the interval of 1 week between the courses. A total of 3 courses of treatment were required. The social domain of the autism treatment evaluation checklist (ATEC) and the autism behavior checklist (ABC) were adopted to assess the therapeutic effect of the two groups. RESULTS: After treatment, the scores of each item of the social domain in ATEC and the scores of ABC (feeling, communication, physical movement, language and healthy behavior) were all lower than those before treatment in the two groups (P<0.01). The scores of each item in the observation group were lower than those in the control group after treatment (P<0.05). CONCLUSION: The combined treatment of acupoint catgut embedding therapy with the rehabilitation training effectively improves in the joint attention and social communication. The therapeutic effect of this combined treatment is better than the simple application of rehabilitation training.
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Terapia por Acupuntura , Atenção , Transtorno do Espectro Autista/terapia , Categute , Comunicação , Pontos de Acupuntura , Criança , HumanosRESUMO
ß-Carotene is a natural nutrient that serves as a natural food colorant. However, the weak physical stability restricts its development in food industrial production. Here, the influences of a variety of external environmental conditions on the stability of ß-carotene enriched zein-carboxymethyl chitosan (CMCS)-tea polyphenols (TP) ternary composite nanoparticles were investigated. Compared with zein unitary and zein-CMCS binary complexes, it was interesting to note that ternary complexes had the best stability against color fading and there was little impact on its nanoparticle size during storage with change in temperature. Besides excellent antioxidant properties, ternary complexes were extremely effective in inhibiting ß-carotene color degradation when exposed to ultraviolet light. Based on our results, the novel zein-CMCS-TP nanoparticles are expected to be an effective delivery system to encapsulate hydrophobic bioactive compounds, which is a promising approach to improve their storage stability against external environmental stresses.
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Quitosana/análogos & derivados , Nanopartículas/química , Polifenóis/química , Zeína/química , beta Caroteno/química , Antioxidantes/química , Quitosana/química , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Concentração Osmolar , Tamanho da Partícula , Chá/química , Temperatura , Raios UltravioletaRESUMO
The optimization of more sustainable fertilization practice to relieve phosphorus (P) resource scarcity and increase P fertilizer utilization, a better understanding of the regulatory roles of microbes in P mobilization is urgently required to reduce P input. The genes phoD and pqqC are responsible for regulating organic and inorganic P mobilization, respectively. Using high-throughput sequencing, the corresponding bacterial communities harbored by these genes were determined. We conducted a 4-year rice-rice-crop rotation to investigate the responses of phoD- and pqqC-harboring bacterial communities to the partial replacement of inorganic P fertilizer by organic manure with reduced P input. The results showed that a combination of organic and inorganic fertilization maintained high rice yield, and also produced a more complex and stable phosphate mobilizing bacterial community, which contributed to phosphatase activities more than their gene abundances in the model analysis. Compared with the conventional mineral fertilization, organic-inorganic fertilization with the reduced P input slightly increased pqqC gene abundance while significantly enhanced the abundance of phoD-harboring bacteria, especially the genera Bradyrhizobium and Methylobacterium known as potential organic P mineralizers which can maintain high rice production. Moreover, the increased pH was the most impactful factor for the phoD- and pqqC-harboring bacterial communities, by promoting microbial P turnover and greatly increasing bioavailable P pools (H2O-Pi and NaHCO3-Pi, NaOH-Pi) in this P-deficient paddy soil. Hence, our study demonstrated that the partial replacement of mineral P with organic manure could reshape the inorganic phosphate solubilizing and alkaline-phosphomonoesterase encoding bacterial communities towards more resilient and effective to the high P utilization and productivity over intense cultivation, providing insights into the potential of soil microbes in the efficient management of agricultural P fertilization.
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Agricultura/métodos , Fósforo/análise , Microbiologia do Solo , Fertilizantes/análise , Esterco , SoloRESUMO
OBJECTIVE: To investigate the effects of Composition of Ophiopogon polysaccharide, Notoginseng total saponins and Rhizoma Coptidis alkaloids (CONR) on myocardial apoptosis of diabetic atherosclerosis (DA) rabbits METHODS: Sixty male New Zealand white rabbits were randomly divided into 6 groups [control group, model group, CONR high-dose group (450 mg/kg), CONR medium-dose group (150 mg/kg), CONR low-dose group (50 mg/kg), and simvastatin group] by using a completely random method, 10 in each group. DA model was established by intravenously injected alloxan combined with high-fat diet and abdominal aortic balloon injury. After mediation for 10 weeks, fasting blood glucose (FBG), glycosylated hemoglobin (GHB), glycosylated serum protein (GSP), fructoseamine (FRA), aldose reductase (AR), advanced glycation end products (AGEs) in serum were measured by enzyme linked immunosorbent assay (ELISA) method; the expression of receptor of AGEs (RAGE) in myocardial tissue were observed by immunohistochemical method; and p-Jun N-terminal kinase (p-JNK), caspase-3, B-cell lymphoma-2 (bcl-2) protein expression in myocardial tissue were measured by Western blotting. The myocardial apoptosis was detected by TdT-mediated dUTPnick-end labeling (TUNEL) method, and apoptosis index (AI) was calculated. RESULTS: Compared with the control group, serum FBG, GHB, GSP, FRA, AR, AGEs and the expression of myocardium RAGE, p-JNK, caspase-3 proteins, as well as apoptosis index (AI) were significantly increased and bcl-2 protein was significantly decreased in the model group (P<0.01). Compared with the model group, the levels of serum FBG, GHB, GSP, FRA and AR showed a significant decline in CONR high- and medium-dose groups (P<0.01). FBG and GHB showed a significant decline in CONR low-dose group (P<0.01). Compared with the model group, the expression of serum AGEs and myocardium RAGE, p-JNK and caspase-3 protein as well as AI were significantly decreased and bcl-2 protein was significantly up-regulated in all treatment groups (P<0.01); high-dose CONR had the most significant effect on abovementioned indices compared with other treatment groups (P<0.01). Middle-dose CONR had better effect on serum AGEs compared with the low-dose group (P<0.01); middle-dose CONR and simvastatin groups had better effect on the expression of caspase-3, bcl-2 protein, myocardium apoptosis compared with the CONR low-dose group (P<0.01). CONCLUSION: CONR may effectively inhibit myocardial apoptosis on DA rabbits by intervening AGEs-RAGE and JNK, caspase-3, and bcl-2 protein expressions.
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Apoptose/efeitos dos fármacos , Angiopatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Ophiopogon/química , Polissacarídeos/farmacologia , Saponinas/farmacologia , Alcaloides/farmacologia , Animais , Aterosclerose , Coptis chinensis , Diabetes Mellitus Experimental , Modelos Animais de Doenças , Coração/efeitos dos fármacos , Masculino , Panax notoginseng/química , CoelhosRESUMO
OBJECTIVE: To investigate the effective of acupoint thread-embedding therapy for ataxia children with cerebral palsy. METHODS: A total of 70 ataxia children with cerebral palsy and a Gross Motor Function Measure (GMFM, Dimension B) score of <35 were enrolled and randomly divided into thread-embedding group and control group, with 35 children in each group, and 2 children in the thread-embedding group were lost to follow-up. The children in the control group were given routine rehabilitation treatment, including physical therapy, spleen-strengthening, kidney-nourishing, and Governor Vessel-regulating massage, vibroacoustic therapy, and scalp acupuncture, and those in the thread-embedding group were given thread-embedding therapy at the acupoints of Jianyu (LI15), Jianliao (SJ14), Tianzong (SI11), Tianshu (ST25), and HuatuoJiaji points (C4, L1 and L4) in addition to the treatment in the control group, with 6-8 acupoints selected each time, once a week. Each course of treatment was 4 weeks, with an interval of one week between two courses of treatment, and the children were treated for 3 courses. Level of sitting scale (LSS), incurvation reflex, and GMFM score were recorded to evaluate the improvement in sitting ability and clinical outcome. RESULTS: Both groups had significant improvements in LSS, incurvation reflex, and GMFM (Dimension A and B) score after treatment (P<0.01), and the thread-embedding group had significantly greater improvements than the control group (P<0.01). The thread-embedding group had a significantly higher overall response rate than the control group (90.9% [30/33] vs 68.5% [24/35], P<0.01). CONCLUSION: In addition to routine rehabilitation treatment, acupoint thread-embedding therapy can effectively suppress primitive reflex in ataxia children with cerebral palsy and significantly promote their sitting ability, and therefore, it is an effective acupuncture treatment method for ataxia children with cerebral palsy.
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Pontos de Acupuntura , Paralisia Cerebral , Ataxia , Paralisia Cerebral/terapia , Criança , Humanos , Postura SentadaRESUMO
The design of zein-based nanoparticles to encapsulate bioactive molecules has gained great attention in recent years. However, the use of ethanol to dissolve zein presents flammability concerns and the scale-up production of zein-based nanoparticles is also a concern. In our study, propolis loaded zein/caseinate/alginate nanoparticles were fabricated using a facile one-step procedure: a well-blended solution was prepared containing deprotonated propolis, soluble zein, dissociated sodium caseinate micelles (NaCas) and alginate at alkaline pH, and then this alkaline solution was added to 0.1 M citrate buffer (pH 3.8) to fabricate composite nanoparticles without using organic solvents and sophisticated equipment. During acidification, the alginate molecules adsorbed on the zein/NaCas surfaces by electrostatic complexation, which improved the stability towards aggregation of zein/NaCas nanoparticles under gastrointestinal (GI) or acidic pH. The nanoparticles prepared under the optimized method (method 3 sample) were of spherical morphology with a particle size around 208 nm and a negative zeta potential around -27 mV. The encapsulation efficiency (EE) and loading capacity (LC) of propolis reached 86.5% and 59.6 µg mg-1 by zein/NaCas/alginate nanoparticles, respectively. These nanoparticles were shown to be stable towards aggregation over a wide range of pH values (2-8) and salt concentrations (0-300 mM NaCl). Compared to free propolis, the bioaccessibility of propolis encapsulated with nanoparticles was increased to 80%. Our results showed a promising clean and scalability strategy to encapsulate hydrophobic nutraceuticals for applications in foods, supplements, and pharmaceuticals.
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Alginatos/química , Caseínas/química , Nanopartículas/química , Própole/química , Zeína/química , Tecnologia de Alimentos , Microscopia Eletrônica de TransmissãoRESUMO
BACKGROUND: Herbal tea is widely consumed in Jianghua, a Yao autonomous county in Hunan Province, China, to prevent and treat diseases. The materials in herbal tea at the traditional medicinal markets at the Dragon Boat Festival remain unknown. The aims of the paper were (1) to specifically investigate the materials of herbal tea used by Yao nationalities in Hunan Province, (2) to record the most common and the culturally important medicinal plant species in the markets, and (3) to compare the medical plant tradition both used for herbal tea between the Jianghua and Lingnan regions. METHODS: During 2016-2017, 215 vendors were interviewed at traditional medicinal markets at the Dragon Boat Festival in Jianghua to record plants used for herbal tea and to document traditional knowledge of their medicinal function, habitat, and conservation status. Bunches of medicinal plants were purchased to identify the species and to prepare voucher specimens. Cognitive salience (CS) based on free-lists and use value (UV) were calculated to analyze the cultural importance of medical plants; other quantitative methods (coefficient of similarity and chi-square analysis) were applied for comparison of herbal tea tradition between the Jianghua and Lingnan regions. RESULTS: A total of 169 species belonging to 66 families and 142 genera were recorded in herbal tea to treat health conditions in the study area. There were 30 health conditions that were recorded, with heat-clearing and detoxifying being the most common medicinal function, followed by treating rheumatism and promoting blood circulation. Of the 169 species, 97 were herbs. The whole plant was the most commonly used plant part in the preparation of herbal tea. According to the national evaluation criteria, three of these species are listed on "China's red list" and registered as vulnerable (VU). By comparing the coefficient of similarity of herbal tea plants and the number of mentions for part(s) used in Jianghua and Lingnan, the medicinal plant tradition is different in two areas. CONCLUSIONS: Herbal tea in Jianghua reflects the cultural diversity of the Yao people and the plant diversity of the region. Future research on the safety, efficacy, and the adulterants of herbal tea are needed for sustainable utilization.
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Comércio , Etnobotânica , Medicina Tradicional Chinesa , Plantas Medicinais , Chás de Ervas , China , Cultura , Férias e FeriadosRESUMO
Currently, combination drug therapy is one of the most effective approaches to glioma treatment. However, due to the inherent dissimilar pharmacokinetics of individual drugs and blood brain barriers, it was difficult for the concomitant drugs to simultaneously be delivered to glioma in an optimal dose ratio manner. Herein, a cationic micellar core (Cur-M) was first prepared from d-α-tocopherol-grafted-ε-polylysine polymer to encapsulate the hydrophobic curcumin, followed by dopamine-modified-poly-γ-glutamic acid polymer further deposited on its surface as a anion shell through pH-sensitive linkage to encapsulate the hydrophilic doxorubicin (DOX) hydrochloride. By controlling the combinational Cur/DOX molar ratio at 3:1, a pH-sensitive core-shell nanoparticle (PDCP-NP) was constructed to simultaneously target the cancer stem cells (CSCs) and the differentiated tumor cells. PDCP-NP exhibited a dynamic diameter of 160.8 nm and a zeta-potential of -30.5 mV, while its core-shell structure was further confirmed by XPS and TEM. The ratiometric delivery capability of PDCP-NP was confirmed by in vitro and in vivo studies, in comparison with the cocktail Cur/DOX solution. Meanwhile, the percentage of CSCs in tumors was significantly decreased from 4.16% to 0.95% after treatment with PDCP-NP. Overall, PDCP-NP may be a promising carrier for the combination therapy with drug candidates having dissimilar physicochemical properties.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/química , Glioma/tratamento farmacológico , Nanopartículas/química , Animais , Linhagem Celular Tumoral , Curcumina/administração & dosagem , Curcumina/química , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Ácido Glutâmico/química , Humanos , Concentração de Íons de Hidrogênio , Masculino , Micelas , Células-Tronco Neoplásicas/efeitos dos fármacos , Polilisina/química , Polímeros/química , Ratos , Ratos Sprague-Dawley , alfa-Tocoferol/químicaRESUMO
Streptochlorin, a small indole alkaloid isolated from marine Streptomyces sp., exhibits a wide range of potent biological activities. An efficient and economic synthetic protocol for streptochlorin has been developed and validated, 4 steps from indole in a total yield of 45%, and further applied for the synthesis of its analogues. Biological testing showed that most of the target compounds exhibited potential antifungal activity in the primary assays, especially compounds 6, 7 and 9c were the most active ones, representing effective activity against the phytopathogenic fungi screened in preliminary test and might be explored for the study of mode of action in the future.
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Fungicidas Industriais/síntese química , Fungicidas Industriais/farmacologia , Indóis/síntese química , Indóis/farmacologia , Oxazóis/síntese química , Oxazóis/farmacologia , Fungos/efeitos dos fármacos , Estrutura Molecular , Streptomyces/química , Relação Estrutura-AtividadeRESUMO
A poor percutaneous penetration capability for most topical anti-inflammatory drugs is one of the main causes compromising their therapeutic effects on psoriatic skin. Even though curcumin has shown a remarkable efficacy in the treatment of psoriasis, its effective penetration through the stratum corneum is still a major challenge during transdermal delivery. The aim of our study was to design skin-permeating nanoparticles (NPs) to facilitate delivery of curcumin to the deeper layers of the skin. A novel amphiphilic polymer, RRR-α-tocopheryl succinate-grafted-ε-polylysine conjugate (VES-g-ε-PLL) was synthesized and self-assembled into polymeric nanoparticles. The nanoparticles of VES-g-ε-PLL exhibiting an ultra-small hydrodynamic diameter (24.4nm) and a positive Zeta potential (19.6mV) provided a strong skin-penetrating ability in vivo. Moreover, curcumin could effectively be encapsulated in the polymeric nanoparticles with a drug loading capacity of 3.49% and an encapsulating efficiency of 78.45%. In order to prolong the retention time of the ultra-small curcumin-loaded nanoparticles (CUR-NPs) in the skin, silk fibroin was used as a hydrogel-based matrix to further facilitate topical delivery of the model drug. In vitro studies showed that CUR-NPs incorporated in silk fibroin hydrogel (CUR-NPs-gel) exhibited a slower release profile of curcumin than the plain CUR-gel, without compromising the skin penetration ability of CUR-NPs. In vivo studies on miquimod-induced psoriatic mice showed that CUR-NPs-gel exhibited a higher therapeutic effect than CUR-NPs as the former demonstrated a more powerful skin-permeating capability and a more effective anti-keratinization process. CUR-NPs-gel was therefore able to inhibit the expression of inflammatory cytokines (TNF-α, NF-κB and IL-6) to a greater extent. In conclusion, the permeable nanoparticle-gel system may be a potential carrier for the topical delivery of lipophilic anti-psoriatic drugs.
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Curcumina/administração & dosagem , Fibroínas/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Nanopartículas/química , Psoríase/tratamento farmacológico , Pele/metabolismo , Administração Cutânea , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Curcumina/química , Curcumina/farmacocinética , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos/métodos , Humanos , Masculino , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Tamanho da Partícula , Polímeros/química , Psoríase/patologia , Seda/químicaRESUMO
Severe toxicity and poor tumour penetration are two intrinsic limited factors to hinder the broad clinical application for most of first-line chemotherapeutics. In this study, a novel vitamin E succinate-grafted ε-polylysine (VES-g-PLL) polymer was synthesized by using ε-polylysine as backbone. By adjusting VES graft ratio, VES-g-PLL (50) with a theoretic VES graft ratio of 50% could self-assemble into a supermolecular micelle with a hydrodynamic diameter (Dh) of ca.20nm, and Zeta potential of 19.6mV. VES-g-PLL micelles themselves displayed a strong anti-tumour effect on glioma. The poorly water-soluble curcumin was effectively encapsulated in VES-g-PLL micelles with the drug loading amount and entrapment efficiency reaching 4.32% and 82.27%, respectively. In a physiologic medium, curcumin-loaded VES-g-PLL micelles (Cur-Micelles) not only remained stable without obvious drug leakage but also sustained the release of its encapsulated curcumin for a long time. Because of the ultra-small size and positively-charged surface, Cur-Micelles penetrated the deeper tumour zone than free curcumin, resulting in a significant inhibition of tumour spheroids growth. Moreover, in vivo strong antitumor effect of Cur-Micelles was also exhibited at assistance of ultrasound-targeted microbubble destruction and the real-time MRI imaging demonstrated a nearly complete suppression of glioma after 28days of treatment. TUNEL staining showed that the therapeutic mechanism of Cur-Micelles was relevant to the apoptosis of tumour cells. Finally, in vivo nontoxicity of Cur-Micelles against normal organs including heart, liver, spleen, lung and kidney tissues was also demonstrated by the HE staining. In conclusion, VES-g-PLL micelles may serve as a potential carrier for curcumin to enhance tumour penetration and improve therapeutic effect on glioma.
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Curcumina/química , Micelas , Polilisina/química , Apoptose/efeitos dos fármacos , Curcumina/farmacologia , Glioma/metabolismo , Humanos , Marcação In Situ das Extremidades Cortadas , Rim/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , Células MCF-7 , Baço/metabolismo , alfa-Tocoferol/análogos & derivados , alfa-Tocoferol/metabolismoRESUMO
OBJECTIVE Lychee seed, a famous traditional Chinese medicine, recently were reported to improve the learning and memory abilities in mice. However, it is still unclear whether lychee seed saponins (LSS) can improve the cognitive function and associated mechanisms. METHODS In present studies, we established the Alzheimer disease (AD) model by injecting Aβ25-35 into the lateral ventricle of rats. Then the spatial learning and memory abilities of LSS- treated rats were evaluated with the Morris water maze, meanwhile the protein expressions of AKT, GSK3β and Tau in the hippo?campal neuron were analyzed by immunohistochemistry and Western blotting. RESULTS The results showed LSS can improve the cognitive functions of AD rats through shortening the escape latency, increasing the number across the platform, platform quadrant dwell time and the percentage of the total distance run platform quadrant. The protein expression of AKT was significantly up-regulated and that of GSK3β and Tau were decreased remarkably in the hippocampal CA1 area. CONCLUSION Our study is the first to show that LSS significantly improve the cognitive function and prevent hippocampal neuronal injury of the rats with AD by activation of the PI3K/AKT/GSK3β signaling pathway, suggesting LSS may be developed into the nutrient supplement for the treatment of AD.
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Molecular imaging enables noninvasive characterization, quantification and visualization of biological and pathological processes in vivo at cellular and molecular level. It plays an important role in drug discovery and development. The skillful use of molecular imaging can provide unique insights into disease processes, which greatly aid in identifications of target. Importantly, molecular imaging is widely applied in the pharmacodynamics study to provide earlier endpoints during the preclinical drug development process, since it can be applied to monitor the effects of treatment in vivo with the use of biomarkers. Herein, we reviewed the application of molecular imaging technologies in antitumor drug development process ranging from identification of targets to evaluation of therapeutic effect.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Descoberta de Drogas/métodos , Imagem Molecular/métodos , Neoplasias/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Descoberta de Drogas/tendências , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/tendências , Humanos , Imagem Molecular/tendências , Neoplasias/diagnósticoRESUMO
OBJECTIVE: To evaluate the effects and influencing factors of mass chemotherapy in the late stage of soil-borne nematodiasis control so as to provide the evidence for the development of control programs. METHODS: Six villages were divided into three groups: the target chemotherapy, the selective chemotherapy and the control. By observation in three consecutive years, the indexes, mass infection rates, infection degrees and re-infections of soil-borne nematodes, were compared among the 3 groups. The influencing factors were also analyzed. RESULTS: The population infection rates of soil- borne nematodes decreased by 85.94%, 43.10% and 20.87%, respectively, in the three groups after chemotherapy compared with those before the intervention. A higher hookworm infection rate appeared and the chemotherapy effect was impacted in the target chemotherapy group, as some key population applied fresh human waste in vegetable plots. The re-infection rate was 16.65 times of the new infection rate. CONCLUSIONS: Chemotherapy is still useful in the late stage of soil-borne nematode control. It is more important to enhance management of using manure and health education on focus population.
Assuntos
Antinematódeos/uso terapêutico , Infecções por Nematoides/tratamento farmacológico , Solo/parasitologia , Adolescente , Adulto , Animais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nematoides/efeitos dos fármacos , Nematoides/fisiologia , Infecções por Nematoides/epidemiologia , Infecções por Nematoides/parasitologia , Adulto JovemRESUMO
OBJECTIVE: To verify the efficacy on autism treated with scalp acupuncture for regaining the consciousness and opening the orifice in children. METHODS: Seventy cases of child autism were divided into an observation group (30 cases) and a control group (40 cases). In observation group, the cases were treated with scalp acupuncture for regaining the consciousness and opening the orifice, in combination with music therapy and structure education method. Scalp acupuncture was applied to intelligent nine needles (frontal five needles, Sishencong (EX-HN 1)), affection area, heart and liver area, once a day, at the interval once every one week. Totally, 60 treatments made one session. In control group, music therapy and structure education method were applied simply. Clancy Autism Behavior Scale, Childhood Autism Behavior Scale (CARS), Autism Behavior Checklist (ABC) and Gesell Developmental Scale (social adaptive behaviors and language development) were adopted to assess the scores before treatment and after 1 session of treatment. RESULTS: After treatment, the scores in Clancy Autism Behavior Scale, CARS and ABC were lower apparently in observation group as compared with those before treatment (all P < 0.01), and the scores in Clancy Autism Behavior Scale and ABC were lower than those in control group (both P < 0.01). In observation group, the scores of social adaptive behavior scale and language development scale were improved obviously after treatment (both P < 0.01), which were all higher than those in control group (both P < 0.01). In observation, between the group aged from 4 to 6 years and the group aged from 2 to 3 years, the value differences in Clancy Autism Behavior Scale, ABC and social adaptive development scale did not present statistical significance in group comparison before and after treatment (all P > 0.05). CONCLUSION: Scalp acupuncture for regaining the consciousness and opening the orifice can significantly improve the efficacy on autism, effectively relieve child autism symptoms and enhance the intelligence, language ability and social adaptive ability. Moreover, the efficacy cannot be impacted by child's age.
Assuntos
Terapia por Acupuntura , Transtorno Autístico/terapia , Couro Cabeludo , Adaptação Psicológica , Transtorno Autístico/psicologia , Comportamento Infantil , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
In the present paper, the authors introduce the development of researches on the specificity of acupoints in morphological structure (nerves, blood vessels, musculotendons, connective tissues, etc), biophysical characteristics (electricity, sonics, photology, thermology, electromagnetism), pathological response, and effectiveness. However, the aforementioned researches are basically at the stage of phenomenon-observation, some key factors influencing acupoint specificity and the underlying mechanisms have no definite or lack convincing results. Further studies should aim at those acupoints for some effective diseases (or symptoms) of acupuncture by using multiple modern scientific techniques. Some key scientific issues about the biophysical characteristics, pathological responses, efficacy, and combination regularity of acupoints should be solved reasonably. Moreover, theoretical models about acupoint specificity should be established for developing the theory of acupoint learning.