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1.
J Nanobiotechnology ; 22(1): 146, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38566213

RESUMO

Thrombotic diseases impose a significant global health burden, and conventional drug-based thrombolytic therapies are encumbered by the risk of bleeding complications. In this study, we introduce a novel drug-free nanomedicine founded on tea polyphenols nanoparticles (TPNs), which exhibits multifaceted capabilities for localized photothermal thrombolysis. TPNs were synthesized through a one-pot process under mild conditions, deriving from the monomeric epigallocatechin-3-gallate (EGCG). Within this process, indocyanine green (ICG) was effectively encapsulated, exploiting multiple intermolecular interactions between EGCG and ICG. While both TPNs and ICG inherently possessed photothermal potential, their synergy significantly enhanced photothermal conversion and stability. Furthermore, the nanomedicine was functionalized with cRGD for targeted delivery to activated platelets within thrombus sites, eliciting robust thrombolysis upon laser irradiation across diverse thrombus types. Importantly, the nanomedicine's potent free radical scavenging abilities concurrently mitigated vascular inflammation, thus diminishing the risk of disease recurrence. In summary, this highly biocompatible multifunctional nanomaterial holds promise as a comprehensive approach that combines thrombolysis with anti-inflammatory actions, offering precision in thrombosis treatment.


Assuntos
Nanomedicina , Trombose , Humanos , Polifenóis/farmacologia , Chá , Terapia Trombolítica , Verde de Indocianina/farmacologia , Verde de Indocianina/uso terapêutico , Inflamação/tratamento farmacológico , Trombose/tratamento farmacológico
2.
BMC Musculoskelet Disord ; 25(1): 544, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010006

RESUMO

OBJECTIVE: We aimed to compare the clinical efficacy of inverted triangular cannulated compression screws combined with Gotfried positive or negative buttress reduction in the healing of femoral neck fractures. METHODS: Between October 2017 and March 2021, 55 patients with femoral neck fractures underwent treatment using inverted triangular cannulated compression screws combined with Gotfried positive or negative buttress reduction. Among these patients, 29 received inverted triangular cannulated compression screws combined with Gotfried positive buttress reduction treatment. This group consisted of 16 males and 13 females, with an average age of 43.45 ± 8.23 years. Additionally, 26 patients received inverted triangular cannulated compression nails combined with Gotfried negative buttress reduction treatment. This group included 14 males and 12 females, with an average age of 41.96 ± 8.69 years. Postsurgery, various measurements were taken, including the degree of shortening of the femoral neck, degree of bone nonunion, degree of fixation failure, degree of ischemic necrosis of the femoral head, and Harris score of the hip joint. RESULTS: All patients were followed up for a minimum of 18 months. The group that underwent treatment with an inverted triangular cannulated compression screw combined with Gotfried positive buttress reduction did not experience any cases of bone nonunion, fixation failure, or ischemic necrosis of the femoral head. In the group that received treatment with inverted triangle cannulated compression screws combined with Gotfried negative buttress reduction, there was one case of bone nonunion, three cases of early fixation failure, and one case of ischemic necrosis. Ultimately, five patients (19.23% of the total) underwent joint replacement surgery. The average shortening lengths in the vertical plane were 4.07 ± 1.98 mm and 8.08 ± 3.54 mm, respectively. In the horizontal plane, the average shortening lengths were 3.90 ± 1.57 mm and 7.77 ± 3.31 mm, respectively. At the last follow-up, the group that received Gotfried positive buttress reduction had a greater Harris hip joint score. CONCLUSION: The success rate of combining inverted triangular cannulated compression screws with Gotfried positive buttress reduction surgery is relatively high. This surgical approach effectively prevents femoral neck shortening and improves hip joint function. Moreover, it is crucial to avoid negative buttress reduction when managing femoral neck fractures.


Assuntos
Parafusos Ósseos , Fraturas do Colo Femoral , Consolidação da Fratura , Humanos , Fraturas do Colo Femoral/cirurgia , Fraturas do Colo Femoral/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Estudos Retrospectivos , Seguimentos
3.
Biochem Biophys Res Commun ; 623: 81-88, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35878427

RESUMO

The transcription factor HOXB13 is bound up with the occurrence, progression and drug fast of many kinds of cancer. Nevertheless, the specific molecular mechanism of HOXB13 in hepatocellular carcinoma (HCC) is still unknown. This provides an obstacle to the exploration of HCC treatments targeting HOXB13. This study found that HOXB13 was up-regulated in HCC tissues. HOXB13 enhanced the multiplication and metastasis of HCC cells. It enhanced HCC cell drug and anoikis resistance. The analysis of HCC RNA seq data indicated that the expression of HOXB13 and PIMREG were positively correlated. Luciferase report assay showed that HOXB13 could activate PIMREG promoter transcription. The results of RT-qPCR and western blot showed that HOXB13 regulated the transcription of PIMREG. Western blot proved that high expression of PIMREG participated in DNA damage repair and cell cycle regulation by up-regulating RAD51, BRCA1, CDC25A, CDC25B and CDC25C and down-regulating HIPK2. This led to a significant increase in DNA repair capacity, accelerated cell cycle progression, and insensitive to DNA damage. Down-regulation of PIMREG in Hep3B cells overexpressing HOXB13 attenuated the phenotype induced by HOXB13. Therefore, HOXB13 functioned through PIMREG instead of directly regulating the transcription of RAD51, BRCA1, CDC25A, CDC25B and CDC25C. The same results were obtained in vivo. It was concluded that HOXB13 affected the expression of cell cycle and DNA repair related factors by up-regulating the transcription of PIMREG, thereby promoting the progression of HCC and enhancing the resistance of HCC to chemotherapeutics.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Resistência a Medicamentos , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias Hepáticas/patologia , Proteínas Nucleares , Proteínas Serina-Treonina Quinases , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
4.
Cancer Immunol Immunother ; 71(8): 2007-2028, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34982184

RESUMO

Although therapeutic cancer vaccines have been gaining substantial ground, the development of cancer vaccines is impeded because of the undegradability of delivery systems, ineffective delivery of tumor antigens and weak immunogenicity of adjuvants. Here, we made use of a whole glucan particle (WGP) to encapsulate ovalbumin (OVA), thereby formulating a novel cancer vaccine. Results from in vitro experiments showed that WGP-OVA not only induced the activation of bone marrow-derived macrophages (BMDMs) including driving M0 BMDM polarization to the M1 phenotype, upregulating the costimulatory molecules and inducing the generation of cytokines, but also facilitated antigen presentation. After oral administration of the WGP-OVA formulation to mice with OVA-expressing tumors, these particles can increase tumor-infiltrating OVA-specific CD8+ CTLs and repolarize tumor-associated macrophages (TAMs) toward M1-like phenotype, which led to delayed tumor progression. These findings revealed that WGP could serve as both an antigen delivery system and an adjuvant system for promising cancer vaccines.


Assuntos
Vacinas Anticâncer , Neoplasias , Adjuvantes Imunológicos , Administração Oral , Animais , Glucanos/farmacologia , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/terapia , Ovalbumina
5.
Anal Bioanal Chem ; 413(3): 935-943, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33210176

RESUMO

The synthesis of fascinating multifunctional carbon dots (CDs) attracted immense attention. Here, a facile solvothermal treatment of red pitaya peels in acetic acid produced CDs (designated as ACDs, excitation/emission wavelengths at 357/432 nm). ACDs with high sp2-hybridized carbon and carboxylic group contents can rapidly and selectively reduce Au3+ to Au0, and stabilize produced Au nanoparticles (AuNPs). The synergetic effect of electron transfer from ACDs to Au3+ and inner filter effect (IFE) from ACDs to AuNPs quenches the fluorescence within 30 s. Simultaneously, the resulting AuNPs have a purple color with a maximum absorption at 545 nm for visual detection. Therefore, for the first time, we reported a fluorometric and colorimetric dual-mode sensing system for real-time, highly sensitive and selective detection of Au3+. The fluorescence quenching ratio and absorbance change linearly with the increase of Au3+ concentration in the range of 0.3-8.0 µM and 3.3-60.0 µM with limits of detection (LODs) at 0.072 µM and 2.2 µM, respectively. The assay was applied for Au3+ determination in spiked real water samples with recoveries from 95.5 to 105.0%, and relative standard deviation (RSD) of less than 6.5%. Furthermore, ACDs with good photostability, low cytotoxicity, and excellent biocompatibility were successfully applied for intracellular Au3+ sensing and imaging. In addition, ACDs exhibited an extraordinarily high antioxidant activity, with an IC50 value for DPPH radical scavenging (0.70 µg mL-1) much lower than that of ascorbic acid (4.34 µg mL-1). The proposed strategy demonstrates the outstanding properties of ACDs in chemical and biomedical analysis. Graphical abstract.


Assuntos
Antioxidantes/farmacologia , Cactaceae/química , Carbono/química , Colorimetria/métodos , Fluorometria/métodos , Ouro/análise , Pontos Quânticos/química , Células HeLa , Humanos , Limite de Detecção , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Análise Espectral/métodos , Difração de Raios X
6.
Bioconjug Chem ; 31(10): 2446-2455, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-32991164

RESUMO

Benzylguanidine, a small cationic and amphiphilic molecule, exhibits a high affinity to C-X-C chemokine receptor type 4 (CXCR 4) and a membrane penetration ability. It has not been used as a functional moiety of nanocarriers for the systemic delivery of chemotherapeutic drugs in tumor therapy. In this study, we investigated the membrane penetration of benzylguanidine-conjugated nanocarriers and their efficiency and safety for targeted delivery of doxorubicin (DOX) in CXCR 4 positive tumors. We conjugated the benzylguanidine bearing guanidinobenzoic acid onto the cystamine bismethacrylamide cross-linked chitosan-poly(methyl methacrylate) nanoparticles, which were then decorated with lactobionic acid (abbreviated as LGCC NPs). A small proportion of LGCC NPs were able to directly penetrate the plasma membrane to enter cells, thereby circumventing endocytic vesicles. The DOX-loaded LGCC NPs (LGCC NPs/DOX) displayed good stability under extracellular physiological conditions and reduction-triggered drug release under high glutathione (GSH) concentration. Moreover, LGCC NPs/DOX showed an increase in tumor-targeted cellular uptake through receptor-mediated endocytosis, enhanced endo/lysosomal escape, and a high nuclear distribution. More importantly, LGCC NPs/DOX significantly suppressed the in vitro and in vivo proliferation of CXCR 4 positive hepatocarcinoma and breast cancer. The findings provide a guideline for the combined application of benzylguanidine and other functional groups in antitumor nanomedicines.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Galactose/análogos & derivados , Guanidinas/química , Neoplasias/tratamento farmacológico , Receptores CXCR4/metabolismo , Animais , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Quitosana/análogos & derivados , Quitosana/metabolismo , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos , Galactose/metabolismo , Guanidinas/metabolismo , Humanos , Camundongos , Nanopartículas/química , Nanopartículas/metabolismo , Neoplasias/metabolismo
7.
Anal Bioanal Chem ; 412(27): 7683-7684, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32944810

RESUMO

The authors would like to call the reader's attention to the fact that unfortunately the wrong file was published as Fig. 2.

8.
Anal Bioanal Chem ; 412(27): 7481-7489, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32833074

RESUMO

Dual-emission and single-emission carbon dots (DCDs and SCDs) have been simultaneously synthesized by one-pot solvothermal treatment of leek. Different graphitization and surface functionalization were responsible for their distinction in fluorescence characteristics. DCDs with an average size of 5.6 nm exhibited two emissions at 489 and 676 nm under 420-nm excitation. Complexation between DCDs' surface porphyrins and Cu2+ led to quenching of the 676-nm emission, which resulted in the ratiometric determination of Cu2+ with a limit of detection (LOD) of 0.085 µM. SCDs, containing additional sulfur element (0.50%) with an average size of 7.7 nm, presented a single emission at 440 nm under 365-nm excitation. The static quenching and inner filter effects between SCDs and tetracyclines (TCs) made SCDs a fluorescence nanoprobe for TCs' determination with LODs of 0.26-0.48 µM. Applications of DCDs and SCDs for respective determination of Cu2+ and TCs in milk and pig liver samples were successfully demonstrated. Moreover, good photostability, low toxicity, and outstanding biocompatibility made DCDs and SCDs suitable for multicolor cellular imaging. Results indicate that natural products are excellent raw materials to controllably synthesize CDs with prominent physicochemical and fluorescence properties.Graphical abstract.


Assuntos
Carbono/química , Cobre/análise , Fígado/química , Leite/química , Pontos Quânticos/química , Tetraciclinas/análise , Animais , Biomassa , Cátions Bivalentes/análise , Cebolinha-Francesa/química , Análise de Alimentos/métodos , Células HeLa , Humanos , Limite de Detecção , Nanotecnologia , Espectrometria de Fluorescência/métodos , Suínos
9.
Xenobiotica ; 50(9): 1011-1022, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31858877

RESUMO

1. Bupleuri Radix (BR) is a herbal medicine traditionally used orally in oriental countries, which inevitably comes into contact with the intestinal microbiota. However, whether gut microbiota contribute to the biotransformation of BR, and/or the formation of pharmacologically active compounds remains unknown.2. In this study, the main saikosaponins (SAPs) of Bupleurum (including saikosaponin a, b1, b2, c, d, f, h) and BR extract (BRE) were individually incubated with human fecal suspensions (HFS), and metabolic time courses of SAPs and their metabolites by human gut bacteria were systematically characterized.3. Deglycosylation and dehydration were the main metabolic pathways identified for SAPs including newly investigated saikosaponin f (SSf) and saikosaponin h (SSh); dehydration had not been reported previously. A total of 19 dehydrated and deglycosylated metabolites of SAPs were detected and characterized, and 10 of them were newly identified. Moreover, SAPs of BRE were found to be deglycosylated to prosaikogenins. In addition, 13 metabolic pathways related to human gut microbiota were identified for phytochemicals of BRE except for SAPs. Gut microbiota may play a significant role in the biotransformation of BR in humans.


Assuntos
Medicamentos de Ervas Chinesas/metabolismo , Microbioma Gastrointestinal , Biotransformação , Bupleurum , Humanos , Raízes de Plantas
10.
Mikrochim Acta ; 187(5): 307, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32356117

RESUMO

Dual-emissive carbon dots (CDs) were fabricated for dual-channel ratiometric fluorometric determination of pH and mercury ion (Hg2+) and intracellular imaging. Dual-emissive CDs were synthesized by one-pot solvothermal treatment of cabbage. The CDs exhibited two distinctive fluorescence emissions at 500 and 678 nm under single excitation at 410 nm. The green emission (500 nm) had reversible linear response to pH (7.0-12.0) due to deprotonation and protonation of surface functional groups and their non-covalent interactions. On the other hand, the red emission (678 nm) had efficient and selective fluorescence response to Hg2+ by formation of non-emission complex between CDs and Hg2+. The limit of detection (LOD) and limit of quantification (LOQ) for Hg2+ were 6.25 and 20.63 nM, respectively. The CDs have been successfully applied for label-free ratiometric fluorometric determination of pH and Hg2+ in fish and human serum samples with good recoveries (92.0-108.3%). In addition, the CDs had excellent photostability, low cytotoxicity, and good biocompatibility for intracellular imaging. All in all, the system was multi-functional in determination, high in sensitivity, and excellent in selectivity, which demonstrated wide and promising applicability for biosensing and bioimaging in the future. Graphical abstract Schematic presentation of dual-emission carbon dots (CDs) synthesized by solvothermal treatment of cabbage for dual-channel determination of pH and Hg2+.


Assuntos
Fluorometria/métodos , Mercúrio/análise , Pontos Quânticos/química , Animais , Brassica/química , Carbono/química , Peixes , Contaminação de Alimentos/análise , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Limite de Detecção
11.
Mol Cancer ; 17(1): 6, 2018 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-29329543

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) are an important class of functional regulators involved in human cancers development, including gastric cancer (GC). Studying aberrantly expressed lncRNAs may provide us with new insights into the occurrence and development of gastric cancer by acting as oncogenes or tumor suppressors. In this study, we aim to examine the expression pattern of lncRNA HAGLROS in GC and its clinical significance as well as its biological role in tumor progression. METHODS: Bioinformatics analysis and qRT-PCR were performed to detect the relative expression of HAGLROS in GC tissues and cell lines. Gain or loss of function approaches were used to investigate the biological functions of HAGLROS. The effect of HAGLROS on proliferation was evaluated by MTT, colony formation assay and nude mouse xenograft model. Wound healing and Transwell assays were used to study the invasion and migration of GC cells. FISH, RIP, RNA-seq, Luciferase report assays, RNA pulldown and Western blot were fulfilled to measure molecular mechanisms. Results are shown as means ± S.D. and differences were tested for significance using Student's t-test (two-tailed). RESULTS: We screened out HAGLROS, whose expression was significantly increased and correlated with outcomes of GC patients by publicly available lncRNAs expression profiling and integrating analyses. Exogenous down-regulation of HAGLROS expression significantly suppressed the cell proliferation, invasion and migration. Mechanistic investigations showed that HAGLROS was a direct target of transcriptional factor STAT3. Moreover, HAGLROS knockdown decreased mTOR expression and increased autophagy-related genes ATG9A and ATG9B expression. Further investigation showed that HAGLROS regulated mTOR signals in two manners. In the one hand, HAGLROS competitively sponged miR-100-5p to increase mTOR expression by antagonizing miR-100-5p-mediated mTOR mRNA inhibition. On the other hand, HAGLROS interacted with mTORC1 components to activate mTORC1 signaling pathway which was known to be an important negative signal of autophagy. Here activation of mTORC1 signaling pathway by HAGLROS inhibited autophagy, thereby promoted excessive proliferation and maintained the malignant phenotype of GC cells. CONCLUSION: The present study demonstrates that HAGLROS overexpression contributes to GC development and poor prognosis and will be a target for GC therapy and further develop as a potential prognostic biomarker.


Assuntos
Autofagia , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transformação Celular Neoplásica , Bases de Dados Genéticas , Modelos Animais de Doenças , Progressão da Doença , Perfilação da Expressão Gênica , Xenoenxertos , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Motivos de Nucleotídeos , Prognóstico , Ligação Proteica
12.
World J Surg Oncol ; 16(1): 138, 2018 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-30001205

RESUMO

BACKGROUND: Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) values as imaging biomarkers of rectal cancer are currently a hot research spot. The use of ADC values for preoperative judgment of pathological features in rectal cancer has been generally accepted. The image quality evaluation of conventional diffusion is severe deformation, and the measurement of ADC values can easily lead to bias. Readout-segmented echo-planar diffusion-weighted imaging (RESOLVE) provides high signal-to-noise ratio images and significantly reduces distortions caused by magnetosensitive effects. The purpose of this study was to explore the correlations between ADC values of RESOLVE and pathological prognostic factors in rectal adenocarcinoma. METHODS: We collected pathological data of 89 patients with pathologically confirmed rectal adenocarcinoma who directly underwent surgical resection without receiving adjuvant therapy. The patients were grouped according to the pathologic type, gross classification, degree of differentiation, TN stage, and immunohistochemical expression of epidermal growth factor receptor (EGFR). RESULTS: RESOLVE ADC values of rectal cancer were measured at b = 800, and correlations between the RESOLVE ADC values obtained in different groups were analysed. We found that RESOLVE ADC values in the ulcer-type group were significantly higher than those in the eminence-type group. CONCLUSION: RESOLVE ADC values in different pathologic types of rectal cancer were significantly different. RESOLVE ADC values in the EGFR-positive group were significantly lower than those in the EGFR-negative group. There was no significant difference in RESOLVE ADC values between different degrees of pathologic differentiation, TN stages, and positive or negative lymph nodes. The quantitative description of RESOLVE ADC values could be used to assess the biological behaviour of rectal adenocarcinoma.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Imagem Ecoplanar/métodos , Neoplasias Retais/diagnóstico por imagem , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Receptores ErbB/biossíntese , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Retais/metabolismo , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Estudos Retrospectivos
13.
Pharm Res ; 34(12): 2829-2841, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28948461

RESUMO

PURPOSE: The present study is aimed at designing an appropriate co-delivery system for chemotherapeutic drugs and gene drugs with high loading capacity, on-demand release behaviors, efficient endosomal escape, and enhanced nucleic localization, thereby providing efficacious antitumor activity. METHODS: Schiff-base linked imidazole dendritic mesoporous silica nanoparticles (SL-IDMSN) were developed and employed to load doxorubicin (DOX) and survivin shRNA-expressing plasmid (iSur-pDNA) to form nanocomplexes. The nanoparticles were assessed by structural characterization, drug loading and release, cellular uptake, intracellular distribution, gene transfection, in vitro anti-proliferation of hepatoma cells, and in vivo tumor growth inhibition in H-22 tumor bearing mice. RESULTS: SL-IDMSN showed high loading capacity for both DOX and iSur-pDNA due to their hierarchical mesostructures. The cleavage of Schiff-base linkage on SL-IDMSN in the weakly acidic endosomes/lysosomes led to microenvironment-specific release of both DOX and iSur-pDNA. Meanwhile, the imidazole modification could trigger the efficient endosomal escape via proton sponge effect, thereby enhancing nuclear accumulation of iSur-pDNA and gene silencing efficiency. More importantly, these superior performances of SL-IDMSN resulted in their improved inhibitory effects on in vitro cancer cell proliferation and in vivo tumor growth. CONCLUSIONS: SL-IDMSN is a microenvironment-sensitive and biocompatible nanocarrier for the co-delivery of DOX and iSur-pDNA, which might be a promising carrier for co-delivery of chemotherapeutic drugs and gene drugs for synergistic cancer therapy.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Preparações de Ação Retardada/química , Doxorrubicina/administração & dosagem , Proteínas Inibidoras de Apoptose/genética , Neoplasias/terapia , RNA Interferente Pequeno/administração & dosagem , Terapêutica com RNAi , Dióxido de Silício/química , Animais , Antibióticos Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Feminino , Técnicas de Transferência de Genes , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Nanopartículas/química , Neoplasias/genética , Plasmídeos/administração & dosagem , Plasmídeos/genética , Porosidade , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Terapêutica com RNAi/métodos , Survivina
14.
J Gene Med ; 17(10-12): 244-56, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26418829

RESUMO

BACKGROUND: Silencing of excessive secreted tumour necrosis factor (TNF)-α from macrophages might be an effective therapy of ulcerative colitis (UC), which acquires improvements on small interfering RNA (siRNA) delivery vectors. Thus, in the present study, the effects of particle size and binding affinity of four polymeric nanoparticles on siRNA delivery for the treatment of UC were evaluated. METHODS: Galactosylated trimethyl chitosan-cysteine (GTC) nanoparticles of varying particle size and binding affinity for siRNA were prepared and TNF-α siRNA was encapsulated. Their cellular transport was investigated in murine macrophages and Caco-2 cell monolayers were utilized to analysis the intestinal permeation. Finally, in vivo anti-inflammatory efficacy was assessed in a mouse model of UC. RESULTS: Although marginal effects of particle size on the in vitro gene silencing efficiency were detected, GTC nanoparticles with a particle size of 450 nm and stronger binding affinity for siRNA showed reduced intestinal epithelial permeability and enhanced in vivo anti-inflammatory efficacy compared to those with a particle size of 200 nm. By contrast, the delivery processes were significantly affected by the binding affinity for siRNA, where smaller GTC nanoparticles (200 nm) with moderate siRNA binding strength exhibited remarkable cytoplasmic distribution and sufficient intracellular release of siRNA, as well as a sustained in vitro and in vivo gene silencing effect. CONCLUSIONS: Nanoparticles with a particle size of 450 nm or balanced binding affinity for siRNA might be preferable for the treatment of ulcerative colitis.


Assuntos
Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Nanopartículas/química , Fragmentos de Peptídeos/genética , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/química , Fator de Necrose Tumoral alfa/genética , Animais , Anti-Inflamatórios/uso terapêutico , Células CACO-2 , Colite Ulcerativa/genética , Colite Ulcerativa/metabolismo , Colite Ulcerativa/terapia , Inativação Gênica , Humanos , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Nanopartículas/administração & dosagem , Tamanho da Partícula , Permeabilidade , RNA Interferente Pequeno/uso terapêutico
15.
Br J Psychiatry ; 207(6): 495-500, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26382951

RESUMO

BACKGROUND: The long-term outcome of never-treated patients with schizophrenia is unclear. AIMS: To compare the 14-year outcomes of never-treated and treated patients with schizophrenia and to establish predictors for never being treated. METHOD: All participants with schizophrenia (n = 510) in Xinjin, Chengdu, China were identified in an epidemiological investigation of 123 572 people and followed up from 1994 to 2008. RESULTS: The results showed that there were 30.6%, 25.0% and 20.4% of patients who received no antipsychotic medication in 1994, 2004 and 2008 respectively. Compared with treated patients, those who were never treated in 2008 were significantly older, had significantly fewer family members, had higher rates of homelessness, death from other causes, being unmarried, living alone, being without a caregiver and poor family attitudes. Partial and complete remission in treated patients (57.3%) was significantly higher than that in the never-treated group (29.8%). Predictors of being in the never-treated group in 2008 encompassed baseline never-treated status, being without a caregiver and poor mental health status in 1994. CONCLUSIONS: Many patients with schizophrenia still do not receive antipsychotic medication in rural areas of China. The 14-year follow-up showed that outcomes for the untreated group were worse. Community-based mental healthcare, health insurance and family intervention are crucial for earlier diagnosis, treatment and rehabilitation in the community.


Assuntos
Antipsicóticos/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/mortalidade , Adulto , Idoso , Causas de Morte , China , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Fatores de Risco , População Rural , Resultado do Tratamento
16.
Pharm Res ; 32(6): 2038-50, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25534683

RESUMO

PURPOSE: Present study aimed at exploring advantages/disadvantages of amino acid modified trimethylated chitosan in conquering multiple gene delivery obstacles and thus providing comprehensive understandings for improved transfection efficiency. METHODS: Arginine, cysteine, and histidine modified trimethyl chitosan were synthesized and employed to self-assemble with plasmid DNA (pDNA) to form nanocomplexes, namely TRNC, TCNC, and THNC, respectively. They were assessed by structural stability, cellular uptake, endosomal escape, release behavior, nuclear localization, and in vitro and in vivo transfection efficiencies. Besides, sodium tripolyphosphate (TPP) was added into TRNC to compromise certain disadvantageous attributes for pDNA delivery. RESULTS: Optimal endosomal escape ability failed to bring in satisfactory transfection efficiency of THNC due to drawbacks in structural stability, cellular uptake, pDNA liberation, and nuclear distribution. TCNC evoked the most potent gene expression owing to multiple advantages including sufficient stability, preferable uptake, efficient pDNA release, and high nucleic accumulation. Undesirable stability and insufficient pDNA release adversely affected TRNC-mediated gene transfer. However, incorporation of TPP could improve such disadvantages and consequently resulted in enhanced transfection efficiencies. CONCLUSIONS: Coordination of multiple contributing effects to conquer all delivery obstacles was necessitated for improved transfection efficiency, which would provide insights into rational design of gene delivery vehicles.


Assuntos
Quitosana/síntese química , Plasmídeos/metabolismo , Transfecção/métodos , Transporte Ativo do Núcleo Celular , Animais , Arginina , Quitosana/análogos & derivados , Cisteína , Endocitose , Endossomos/metabolismo , Regulação da Expressão Gênica , Genes Reporter , Proteínas de Fluorescência Verde/biossíntese , Proteínas de Fluorescência Verde/genética , Células HEK293 , Histidina , Humanos , Camundongos , Músculo Esquelético/metabolismo , Nanopartículas , Conformação de Ácido Nucleico , Plasmídeos/química , Polifosfatos/química , Fatores de Tempo
17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(10): 2734-9, 2015 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-26904809

RESUMO

This study was performed to establish a method that can quickly and accurately identify adulterated syrup in the pure pineapple juice. A attenuated total internal refraction-fourier transform infrared spectroscopy was used to collect the range of 900 -1 500 cm(-1) infrared spectra of 234 samples pure pineapple juice and adulterated syrup by beet syrup, rice syrup and cassava syrup. By using linear discriminant analysis and support vector machine for the identification model, comparing the full spectral and selected wavelengths based on principal component analysis loading plots of the two models to identify adulteration. Studies showed that the correct rate of validation set by linear discriminant analysis and support vector machine model on full spectral were both higher than 88%, variables were significantly reduced from 312 to 8 after selecting the eight characteristic wavelengths, the correct rate of validation set by linear discriminant analysis model was up to 96.15% and support vector machine was increase to 94.87%. The results demonstrated that the model built using a attenuated total internal refraction-fourier transform infrared spectroscopy in combination with chemometric methods after selected characteristic wavelengths could be used for the identification of the adulterated syrup in the pure pineapple juice.

18.
ScientificWorldJournal ; 2014: 473913, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25247206

RESUMO

The series capacitor compensation is one of the key technologies in the EHV and UHV long distance power transmission lines. This paper analyzes the operation characteristics of the main protection combined with the engineering practice when the transmission line overcompensation due to the series compensation system is modified and analyzes the influence of the transition resistance and the system operation mode on the current differential protection. According to the simulation results, it presents countermeasure on improving the sensitivity of differential current protection.


Assuntos
Simulação por Computador , Fontes de Energia Elétrica , Simulação por Computador/normas , Fontes de Energia Elétrica/normas
19.
Zhongguo Zhong Yao Za Zhi ; 39(3): 531-5, 2014 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-24946562

RESUMO

Compound Wuzhigan capsules is a compound preparation composed of Wuzhigan, Shidagonglao, Gangmei, Shanzhima. A Randomized, double-blind, multi-center, positive parallel control designed to evaluate the clinical efficacy and safety of compound Wuzhigan capsules on anemopyretic cold. One hundred and twenty anemopyretic cold patients were given compound Wuzhigan capsules (test group), 2 capsules one time, three times a day, 119 patients were given compound Wuzhigan tablets (control group) ,4 tablets one time, three times a day; three days of treatment The study showed, the markedly effective rate and total effective rate respectively were 63. 3% and 80% of the test group. For the control group, the markedly effective rate and total effective rate respectively were 72. 5% and 80. 7%. The difference was not statistically significant. Compound Wuzhigan capsules can reduce the dosage, and get better patient compliance.


Assuntos
Resfriado Comum/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Adulto , Cápsulas , Resfriado Comum/complicações , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segurança , Resultado do Tratamento , Adulto Jovem
20.
Pak J Pharm Sci ; 27(3 Suppl): 695-701, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24816700

RESUMO

The bacteria grow in oral cavity and product acids, which could induce dental caries. In this study, in order to obtain the relationship between procyanidin dimers from sorghum episperm (sorghum procyanidins, SPC) and its anticaries effect. The extract of SPC purified by macroporous resin was divided into three parts by gel chromatography, marked as GPC-1, GPC-2, and GPC-3 in order. The ESI-MS and MS/MS analysis indicated that the main composition of GPC-2 was procyanidin dimers. In addition, the capacities of antigrowth and antiacid on Sreptococcus sobrinus 6715 were analysised to investigate the effect of SPC dimers in protecting against dental caries. The results indicated that the minimum inhibitory concentration (MIC) of SPC dimers was 16 mg/mL. Furthermore, the SPC dimers had notable preventive effect < against the acid production of Sreptococcus sobrinus 6715 compared with the control group, which suppressed in a dose-dependent manner by pH decline. These findings indicated that SPC dimers had potential to be used as anticaries preventive medicine due to its strong capacity of antigrowth and antiacid.


Assuntos
Biflavonoides/farmacologia , Catequina/farmacologia , Proantocianidinas/farmacologia , Sorghum/química , Streptococcus sobrinus/efeitos dos fármacos , Biflavonoides/química , Catequina/química , Dimerização , Relação Dose-Resposta a Droga , Concentração de Íons de Hidrogênio , Viabilidade Microbiana/efeitos dos fármacos , Proantocianidinas/química , Espectrometria de Massas por Ionização por Electrospray , Streptococcus sobrinus/crescimento & desenvolvimento
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