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1.
Int J Biol Macromol ; 270(Pt 1): 132276, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38734352

RESUMO

The reuse and development of natural waste resources is a hotspots and challenges in the research of new fiber materials and the resolution of environmental concern globally. Herein, this study aimed to develop a simple and direct manual extraction process to extract Musa core fibers (MCFs) for rapid water conduction and evaporation. Through simple processes such as ring cutting and stretching, this green and non-destructive inside-out extraction strategy enabled Musa fibers to be naturally and harmlessly degummed from natural Musa stems, with good maintenance of the fiber structure and highly helical morphology. The extracted fibers are composed of regularly and closely arranged cellulose nanofibrils in the shape of ribbon spirally arranged multi-filaments, and the single filament is about 2.65 µm. The high-purity fibers exhibit ultra-high tensile strength under a non-destructive extraction process, and the ultimate tensile strength in dry state is as high as 742.95 MPa. The tensile strength is affected by the number of fiber bundles, which shows that tensile strength and tensile modulus is higher than those of vascular bundle fibers in dry or wet condition. In addition, the MCFs membrane indicates good water conductivity, with a water absorption height of 50 mm for the sample in only 60 s. Moreover, the water evaporation rate of MCFs reaches 1.37 kg m-2 h-1 in 30 min, which shows that MCFs have excellent water conductivity and evaporation rate compared with ordinary cotton fibers. These results indicate that MCFs have great potential in replacing the use of chemical methods to extract fibers from vascular bundles, providing an effective way to achieve sustainability in quick-drying applications, as well as in the sustainable development of natural waste resources.


Assuntos
Musa , Resistência à Tração , Água , Água/química , Musa/química , Celulose/química , Nanofibras/química
2.
Mater Horiz ; 11(9): 2095-2105, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38391254

RESUMO

Solar-driven evaporation is promising to address water scarcity. However, preserving the heat inside evaporators instead of allowing run-off, and synergistically utilizing it to wick water from the bulk, is still underexplored. Herein, a dual-functional bridge of longitudinal orientated channels of Al2O3 fibers (AOFs) embedded in a multi-layered nonwoven evaporator was proposed to create a buffer for spontaneous thermal conduction and anti-gravitational water pumping. As a self-floating system with high porosity and flexibility, benefiting from the strong water transporting ability and high thermal conductivity of the AOFs, a superhigh evaporation rate (2.79 kg m-2 h-1 under 1 sun) can be achieved with great stability and durability. This work highlights the potential of promoting thermal management using a large-scale vapour chamber and mass-producible nonwoven technology to prepare a high-performance evaporator for practical applications.

3.
RSC Adv ; 13(44): 30898-30904, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37869382

RESUMO

The proliferation and differentiation of bone mesenchymal stem cells (BMSCs) in vitro are the key properties of bone tissue engineering for biomaterials. In this study, hydroxyapatite (HA) coated porous carbon nanofibres (PCNFs) were prepared to load dexamethasone (DEX) and further improve the differentiation ability of the BMSCs. Various characterisations were applied to reveal the DEX loading efficacy and biocompatibility, especially the differentiation strength. The results showed that HA could be successfully coated on the PCNFs by pretreating the surface using PEG conjugation. With an increase of HA, the particle diameter increased and the DEX loading decreased. In vitro experiments proved higher cell viability, alkaline phosphatase (ALP) activity, calcium nodule secretion ability and the RUNX2 protein expression, indicating that the as-prepared was of great biocompatibility and optimised osteoconductivity, which was attributed to the componential imitation to natural bone and the accelerated BMSCs differentiation. Consequently, the novel DEX loaded and HA coated PCNFs can provide potential applications in bone tissue regeneration.

4.
Front Nutr ; 10: 1156006, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37113291

RESUMO

Background: The clinical value of the controlling nutritional status (CONUT) score has been widely reported in multiple malignancies. The aim of this study is to investigate the association between the CONUT score and clinical outcomes in patients with gastric cancer. Methods: A comprehensive literature search of electronic databases including PubMed, Embase, and Web of Science was performed up to December 2022. The primary endpoints were survival outcomes and postoperative complications. Subgroup analysis and sensitivity analysis were performed during the pooled analysis. Results: Nineteen studies including 9,764 patients were included. The pooled results indicated that patients in the high CONUT group had a worse overall survival (HR = 1.70 95%CI: 1.54-1.87; P < 0.0001; I 2 = 33%) and recurrence-free survival (HR = 1.57; 95%CI: 1.36-1.82; P < 0.0001; I 2 = 30%), and a higher risk of complications (OR = 1.96; 95%CI: 1.50-2.57; P < 0.0001; I 2 = 69%). In addition, a high CONUT score was significantly associated with larger tumor size, higher percentage of microvascular invasion, later TNM stage and fewer patients receiving adjuvant chemotherapy, but not with tumor differentiation. Conclusion: Based on existing evidence, the CONUT score could act as a valuable biomarker to predict clinical outcomes in patients with gastric cancer. Clinicians could use this useful indicator to stratify patients and formulate individual treatment plans.

5.
Front Oncol ; 12: 1036890, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36620576

RESUMO

Background: The pan-immune-inflammation value (PIV) has been reported as a novel prognostic biomarker in multiple malignancies. The aim of this study is to investigate the prognostic value of the PIV in patients with colorectal cancer. Methods: We comprehensively searched electronic databases including PubMed, Embase and Web of Science up to August 2022. The endpoints were survival outcomes. Hazard ratios (HRs) with 95% confidence intervals (CIs) for survival data were collected for analysis. Results: Six studies including 1879 participants were included. A significant heterogeneity in the PIV cut-off value among studies was observed. The combined results indicated that patients in the high baseline PIV group had a worse overall survival (HR=2.09; 95%CI: 1.67-2.61; P<0.0001; I2 = 7%) and progression-free survival (HR=1.82; 95%CI: 1.49-2.22; P<0.0001; I2 = 15%). In addition, early PIV increase after treatment initiation was significantly associated with decreased overall survival (HR=1.79; 95%CI: 1.13-2.93; P=0.01; I2 = 26%), and a trend toward poor progression-free survival (HR=2.00; 95%CI: 0.90-4.41; P=0.09; I2 = 70%). Conclusion: Based on existing evidence, the PIV could act as a valuable prognostic index in patients with colorectal cancer. However, the heterogeneity in the PIV cut-off value among studies should be considered when interpreting these findings.

6.
AAPS PharmSciTech ; 21(7): 271, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33033946

RESUMO

To develop a comprehensive understanding of pharmaceutical drug substance manufacturing (DSM) processes, we conducted a data mining study to examine 50 new drug applications (NDAs) approved in 2010-2016. We analyzed the prevalence of several frequently deployed in-process control (IPC) techniques and postreaction workup procedures, as well as the operational conditions specified for reactions and workups. Our findings show that crystallization and high-performance liquid chromatography (HPLC) were the most commonly used workup steps and in-process controls, respectively, in drug substance manufacturing. On average, each NDA implemented 12.6 in-process controls and 11.3 workups. Operation time for reactions and workup procedures varied from a few minutes to multiple days, though 61% of these were between 1 and 10 h.


Assuntos
Preparações Farmacêuticas/síntese química , Cristalização , Mineração de Dados , Controle de Qualidade
7.
Chem Commun (Camb) ; 56(7): 1026-1029, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31854390

RESUMO

We report here a fully automated, end-to-end, integrated continuous manufacturing process for a small-molecule generic medication with built-in quality assurance. The entire process fits into a box of 30.7 m2 modular footprint and a total residence time of less than 30 h, with a throughput up to 40.3 × 106 tablets per year.


Assuntos
Indústria Farmacêutica/métodos , Preparações Farmacêuticas/síntese química , Indústria Farmacêutica/instrumentação
8.
Leuk Res Rep ; 12: 100186, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31867204

RESUMO

Older adults with acute lymphoblastic leukemia (ALL) continue to have a poor prognosis, in part due to greater chemotherapy-related toxicities. We herein report a 67-year-old man with Philadelphia chromosome (Ph)-negative B-cell ALL, who exhibited refractoriness to 3 different regimens of induction chemotherapy and experienced multiple complications including intracranial bleeding and respiratory failure, who achieved minimal residual disease (MRD)-negative complete response (CR) after a single cycle of inotuzumab ozogamicin (IO). His ALL was characterized by several high-risk mutations, which may have contributed to chemotherapy-refractory disease. Our case supports incorporating IO into front-line induction regimens for older adults with high-risk B-cell ALL.

9.
Med Sci Monit ; 24: 6756-6764, 2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30250016

RESUMO

BACKGROUND Computed tomography perfusion imaging (CTPI) and perfusion-weighted imaging (PWI) are non-invasive technologies that can quantify tumor vascularity and blood flow. This study explored the blood flow information, tumor cell viability, and hydrothoraces in a rabbit pleural VX2-implanted model through use of CTPI, PWI, and DWI. MATERIAL AND METHODS A pleural VX2-implanted model was established in 58 New Zealand white rabbits. CTPI, PWI, and DWI were applied with a 16-slice spiral CT and an Archival 1.5 T dual-gradient MRI. RESULTS Compared with muscle tissue, PV, PEI, and BV of parietal and visceral pleural tumor implantation rabbits showed significant differences. The t values of PV, PEI, and BV between parietal and visceral pleura were 2.08, 2.29, and 2.88, respectively. Compared with muscle tissue, WIR, WOR, and MAXR of parietal and visceral pleural tumor implantation rabbits showed significant differences. In parietal pleural tumor implantation rabbits, the section surface of lesion tissues was 5.2±2.7 cm². Hydrothorax appeared 6.0±2.0 days after tumor implantation. The mean value of ADC was 1.5±0.6. In visceral pleural tumor implantation rabbits, the section surface of lesion tissues was 1.6±0.8 cm². Hydrothorax appeared 7.0±3.0 days after tumor implantation. The mean value of ADC was 1.4±0.5. The t values of the above 3 indices for the parietal and visceral pleura were 1.85, 1.83, and 1.76, respectively (P<0.05). CONCLUSIONS The combined application of CTPI, PWI, and DWI accurately and visually reflects the blood perfusion of tumor tissues and quantitatively analyzes blood flow information and the mechanism underlying hydrothorax generation in tumor tissues.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Neoplasias/diagnóstico por imagem , Neoplasias Pleurais/diagnóstico por imagem , Animais , Imagem de Difusão por Ressonância Magnética/métodos , Modelos Animais de Doenças , Imageamento por Ressonância Magnética/métodos , Imagem de Perfusão/métodos , Coelhos , Tomografia Computadorizada por Raios X/métodos
10.
Exp Ther Med ; 16(2): 1052-1060, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30112050

RESUMO

Compound Astragalus and Salvia miltiorrhiza extract (CASE) is a Chinese herbal formula consisting of astragalosides, astragalus polysaccharide and salvianolic acids extracted from Astragalus membranaceus and Salvia miltiorhiza. Previous studies by our group have demonstrated that CASE effectively suppresses diethylinitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats via modulating transforming growth factor ß/Mothers against decapentaplegic (TGFß/Smad) signaling. To further elucidate the mechanism of CASE, the effects of CASE on TGF-ß1, the serine/threonine kinase receptors of TGF-ß [TGF-ß receptor type-I (TßRI) and TßRII] and karyopherins [Importin 7 (Imp7) and Imp8], which are crucial for TGF-ß/Smad signaling in fibro-hepatocarcinogenesis, were assessed in the present study using in vivo (DEN-induced HCC in rats) and in vitro [TGF-ß1-stimulated rat myofibroblasts (MFBs) and HepG2 cells] models of fibro-hepatocarcinogenesis. Hematoxylin and eosin staining revealed that CASE may suppress inflammatory reactions and fibrosis in HCC as well as increasing the differentiation of HCC cells. Positive TGF-ß1 staining was increased in HCC nodule areas and in adjacent normal liver tissues in DEN-treated rats, while TßRI staining was increased only in normal adjacent liver tissues. The elevated expression of TGF-ß1, TßRI and TßRII was suppressed by CASE. CASE treatment also reduced glutathione S-transferase P 1 and Imp7/8 protein expression in fibro-hepatocarcinogenesis. In vitro experiments confirmed that CASE was able to decrease the expression of TßRI and TßRII in TGF-ß1-stimulated MFBs and HepG2 cells. These results indicate that the anti-HCC effect of CASE may be achieved by mediating TGF-ß/TßR and Imp7/8 protein expression, suggesting that CASE has multiple targets in HCC treatment.

11.
Biomaterials ; 182: 279-288, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30142527

RESUMO

Periosteum plays an indispensable role in bone repair and reconstruction. To recapitulate the remarkable regenerative capacity of periosteum, a biomimetic tissue-engineered periosteum (TEP) was constructed via layer-by-layer bottom-up strategy utilizing polycaprolactone (PCL), collagen, and nano-hydroxyapatite composite nanofiber sheets seeded with bone marrow stromal cells (BMSCs). When combined with a structural bone allograft to repair a 4 mm segmental bone defect created in the mouse femur, TEP restored donor-site periosteal bone formation, reversing the poor biomechanics of bone allograft healing at 6 weeks post-implantation. Further histologic analyses showed that TEP recapitulated the entire periosteal bone repair process, as evidenced by donor-dependent formation of bone and cartilage, induction of distinct CD31high type H endothelium, reconstitution of bone marrow and remodeling of bone allografts. Compared to nanofiber sheets without BMSC seeding, TEP eliminated the fibrotic tissue capsule elicited by nanofiber sheets, leading to a marked improvement of osseointegration at the compromised periosteal site. Taken together, our study demonstrated a novel layer-by-layer engineering platform for construction of a versatile biomimetic periosteum, enabling further assembly of a multi-component and multifunctional periosteum replacement for bone defect repair and reconstruction.


Assuntos
Regeneração Óssea , Substitutos Ósseos/química , Células-Tronco Mesenquimais/citologia , Nanofibras/química , Periósteo/fisiologia , Alicerces Teciduais/química , Animais , Materiais Biomiméticos/química , Biomimética , Colágeno/química , Fêmur/citologia , Fêmur/lesões , Fêmur/fisiologia , Fêmur/ultraestrutura , Transplante de Células-Tronco Mesenquimais/métodos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Nanofibras/ultraestrutura , Periósteo/citologia , Poliésteres/química , Engenharia Tecidual/métodos
12.
Endocrinology ; 157(8): 3058-69, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27267711

RESUMO

Runt-related transcription factor 1 (Runx1), a master regulator of hematopoiesis, is expressed in preosteoclasts. Previously we evaluated the bone phenotype of CD11b-Cre Runx1(fl/fl) mice and demonstrated enhanced osteoclasts and decreased bone mass in males. However, an assessment of the effects of Runx1 deletion in female osteoclast precursors was impossible with this model. Moreover, the role of Runx1 in myeloid cell differentiation into other lineages is unknown. Therefore, we generated LysM-Cre Runx1(fl/fl) mice, which delete Runx1 equally (∼80% deletion) in myeloid precursor cells from both sexes and examined the capacity of these cells to differentiate into osteoclasts and phagocytic and antigen-presenting cells. Both female and male LysM-Cre Runx1(fl/fl) mice had decreased trabecular bone mass (72% decrease in bone volume fraction) and increased osteoclast number (2-3 times) (P < .05) without alteration of osteoblast histomorphometric indices. We also demonstrated that loss of Runx1 in pluripotential myeloid precursors with LysM-Cre did not alter the number of myeloid precursor cells in bone marrow or their ability to differentiate into phagocytizing or antigen-presenting cells. This study demonstrates that abrogation of Runx1 in multipotential myeloid precursor cells significantly and specifically enhanced the ability of receptor activator of nuclear factor-κB ligand to stimulate osteoclast formation and fusion in female and male mice without affecting other myeloid cell fates. In turn, increased osteoclast activity in LysM-Cre Runx1(fl/fl) mice likely contributed to a decrease in bone mass. These dramatic effects were not due to increased osteoclast precursors in the deleted mutants and argue that inhibition of Runx1 in multipotential myeloid precursor cells is important for osteoclast formation and function.


Assuntos
Células Apresentadoras de Antígenos/fisiologia , Diferenciação Celular/genética , Transdiferenciação Celular/genética , Subunidade alfa 2 de Fator de Ligação ao Core/fisiologia , Células Progenitoras Mieloides/fisiologia , Osteoclastos/fisiologia , Fagócitos/fisiologia , Animais , Reabsorção Óssea/genética , Células Cultivadas , Feminino , Hematopoese/genética , Masculino , Camundongos , Camundongos Transgênicos
13.
CrystEngComm ; 17(31): 6044-6052, 2015 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-26306076

RESUMO

Methods to produce nano-sized organic molecular crystals in thin films are of great interest in the pharmaceutical industry due to the potential benefit of increased solubility of poorly soluble drugs and the advantages of film-based dosage forms over traditional tablet/capsule-based dosage form. One method to directly form organic nanocrystals is by crystallization in confined environments where the overall crystallization volume is constrained. We report the use of a novel solution impregnation method to form nanocrystals in polymer matrices with various microstructures in order to study the structure of the confined nanocrystals and the role of soft confinement and polymer chemistry on the nucleation process of nano-sized crystals. The particle diameter correlates with the microstructure of the polymer matrices and the nucleation kinetics. In addition, by carefully choosing the experimental conditions and the polymer matrix, polymorph control of nanocrystals can be achieved. Solid-state nuclear magnetic resonance (ssNMR) was used to examine the local structure of nanocrystals inside the polymer matrices and crystal polymer interactions. This method may serve as a novel formulation method to obtain nanocrystals of poorly soluble active pharmaceutical ingredients (APIs) for pharmaceutical industry.

14.
Burns ; 41(8): 1764-1774, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26187057

RESUMO

Creation of functional skin substitutes within a clinically acceptable time window is essential for timely repair and management of large wounds such as extensive burns. The aim of this study was to investigate the possibility of fabricating skin substitutes via a bottom-up nanofiber-enabled cell assembly approach and using such substitutes for full-thickness wound repair in nude mice. Following a layer-by-layer (L-b-L) manner, human primary skin cells (fibroblasts and keratinocytes) were rapidly assembled together with electrospun polycaprolactone (PCL)/collagen (3:1, w/w; 8%, w/v) nanofibers into 3D constructs, in which fibroblasts and keratinocytes were located in the bottom and upper portion respectively. Following culture, the constructs developed into a skin-like structure with expression of basal keratinocyte markers and deposition of new matrix while exhibiting good mechanical strength (as high as 4.0 MPa by 14 days). Treatment of the full-thickness wounds created on the back of nude mice with various grafts (acellular nanofiber meshes, dermal substitutes, skin substitutes and autografts) revealed that 14-day-cultured skin substitutes facilitated a rapid wound closure with complete epithelialization comparable to autografts. Taken together, skin-like substitutes can be formed by L-b-L assembling human skin cells and biomimetic nanofibers and they are effective to heal acute full-thickness wounds in nude mice.


Assuntos
Materiais Biomiméticos/uso terapêutico , Fibroblastos , Queratinócitos , Nanofibras/uso terapêutico , Poliésteres/uso terapêutico , Pele Artificial , Engenharia Tecidual/métodos , Ferimentos e Lesões/terapia , Derme Acelular , Animais , Proliferação de Células , Prepúcio do Pênis/citologia , Humanos , Recém-Nascido , Masculino , Camundongos , Camundongos Nus , Pele/lesões , Transplante de Pele , Transplante Autólogo , Cicatrização
15.
Mol Cell Biochem ; 406(1-2): 255-62, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25968067

RESUMO

Mitogen-activated protein kinase (MAPK) pathway-dependent linker phosphorylation of Smad2/3 and subsequent formation of Smad2/3/4 complex and its nuclear translocation are crucial for dysregulated transforming growth factor beta (TGF)-ß/Smad signaling in liver fibrosis. Abrogation of this critical step of TGF-ß/Smad signaling leading to liver fibrosis could provide new insights for future therapy, but the mechanisms remain incompletely understood. In pursuit, we investigated the subcellular expression and nuclear trafficking of the rate limiting Smad2/3/4 complex in exogenous TGF-ß1-stimulated myofibroblasts (MFBs) using three MAPK-specific inhibitors. Our results showed that exogenous TGF-ß1 stimulation of MFBs produced both increased protein expression and nuclear translocation of phosphorylated (p)-Smad2C/L, oncogenic pSmad3L, Smad4, importin7/8 (Imp7/8), and plasminogen activator inhibitor (PAI)-1 (Protein and mRNA), while decreased Smad7 protein expression. However, the MAPK-specific inhibitors differentially reversed these observations; for instance, ERK-specific inhibitor blocked the expression and nuclear translocation of pSmad2C/L, while both JNK and p38-specific inhibitors blocked the expression and nuclear translocation of pSmad2C/L and oncogenic pSmad3L. The MAPK-specific inhibitors had no significant effect on the total protein expression of Smad4, but rather significantly blocked its nuclear translocation. All the MAPK-specific inhibitors restored Smad7 expression and also decreased Imp7/8 and PAI-1 (Protein and mRNA) expression. Evidently, the MAPK-specific inhibitors blocked Smad2/3/4 complex formation via restoration of inhibitory Smad7 expression and blockade of Smad3L phosphorylation, while they blocked nuclear translocation of Smad2/3/4 complex through inhibition of Imp7/8 leading to decreased PAI-1 (Protein and mRNA) expression.


Assuntos
Miofibroblastos/metabolismo , Proteínas Smad/metabolismo , alfa Carioferinas/metabolismo , beta Carioferinas/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Antracenos/farmacologia , Células Cultivadas , Flavonoides/farmacologia , Expressão Gênica , Masculino , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Miofibroblastos/efeitos dos fármacos , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/fisiologia , alfa Carioferinas/genética , beta Carioferinas/genética
16.
J Ethnopharmacol ; 169: 219-28, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-25934513

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus membranaceus Bunge (Leguminosae) and Salvia miltiorrhiza Bunge (Lamiaceae) are two important Chinese herbs with a long history of extensive ethnobotanical usage in the treatment of liver-related diseases over many centuries. Presently, these two herbs are being used either as a single herbal formulation or a composite formula for the treatment of liver related conditions. In response, recent studies on these two herbs have focused on elucidating their mechanisms of action, particularly with regards to their anti-hepatocarcinogenic effects. Previously, we have reported that Compound Astragalus and Salvia miltiorrhiza extract (CASE), a synergized composite extract from Astragalus membranaceus and Salvia miltiorrhiza ameliorates liver fibrosis and hepatocellular carcinoma (HCC) by modulating the TGF-ß/Smad pathway. Meanwhile, MAPK activation and MAPK-dependent linker phosphorylation of Smad2/3 and their preferential nuclear import are crucial for overall oncogenic role of TGF-ß/Smad signaling in HCC. To elucidate further, we studied the effect of CASE on the MAPK pathway and how it affects MAPK-dependent regulation of TGF-ß/Smad signaling using both cell and animal models of HCC. MATERIALS AND METHODS: We used immunofluorescence and western blot techniques to monitor effect of CASE on the activation of the MAPKs (pERK, pJNK and pp38) in TGF-ß1-stimulated hepatic stellate cells (HSCs), HepG2 cells and also diethylnitrosamine (DEN)-induced HCC in rats. Also phosphorylation and subcellular distribution of pSmad2/3, Smad4 and Imp7/8 in TGF-ß1-stimulated HSC and HepG2 cells were monitored. The expression of pERK, pJNK, pp38 and PAI-1 gene were monitored by using western blot technique. The effect of CASE on domain-specific phosphorylation of Smad2/3 and their subcellular distribution, and the expression of Smad4 and its subcellular distribution in TGF-ß1-stimulated HSCs and HepG2 cells were evaluated by using immunofluorescence technique. And the expression of Imp7/8 and their subcellular distribution were assessed by both immunofluorescence and western blot techniques, while PAI-1 gene expression was assessed by western blot RESULTS: In vitro, CASE in a concentration-dependent manner increased the expression of pp38 but decreased the expression of pERK and pJNK; however, in vivo, CASE in a dose dependent manner decreased the expression of pERK, pJNK as well as pp38. Also, CASE concentration dependently inhibited pSmad2C/L, pSmad3L, Smad4, Imp7/8 and their nuclear import; it had no effect on pSmad3C in HepG2 cells; significantly decreased PAI-1 gene expression in both in vitro and in vivo. CONCLUSIONS: CASE blocked MAPK activation, MAPK-dependent linker phosphorylation of Smad2/3, Smad4 expression, Imp7 expression and their nuclear import leading to significant down-regulation of PAI-1 gene expression; further highlighting the multi-target anti-HCC effect of CASE and its potential drug candidature.


Assuntos
Astragalus propinquus/química , Carcinoma Hepatocelular/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Extratos Vegetais/farmacologia , Salvia miltiorrhiza/química , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Alcenos/isolamento & purificação , Alcenos/farmacologia , Animais , Carcinoma Hepatocelular/induzido quimicamente , Dietilnitrosamina , Regulação para Baixo , Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Humanos , Carioferinas/metabolismo , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/metabolismo , Masculino , Extratos Vegetais/química , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Polifenóis/isolamento & purificação , Polifenóis/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Ratos , Receptores Citoplasmáticos e Nucleares/metabolismo , Saponinas/isolamento & purificação , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologia , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Regulação para Cima
17.
Artigo em Inglês | MEDLINE | ID: mdl-25641690

RESUMO

In recent years, there has been an increased focus on developing novel drug delivery systems and targeted therapies through the use of nanotechnology and nanomaterials. Such focus is translating to an increasing number of investigational new drug (IND) applications, new drug applications (NDAs), and abbreviated new drug applications (ANDAs) for drug products containing nanomaterials to the United States Food and Drug Administration (FDA). Although subject to the same rigorous regulatory standards and regulatory pathways as any drug product, unique properties that arise from the small size, large surface area, and polydispersity of nanomaterials may lead to additional scientific considerations when following current FDA guidelines and practices for drug evaluation. This review article will discuss these scientific considerations based on the experience with FDA-approved drug products containing nanomaterials.


Assuntos
Nanoestruturas/normas , Animais , Fenômenos Químicos , Desenho de Fármacos , Guias como Assunto , Humanos , Legislação de Medicamentos , Controle Social Formal , Estados Unidos
18.
J Bone Miner Res ; 30(7): 1217-30, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25640220

RESUMO

Osteogenesis and angiogenesis are two integrated components in bone repair and regeneration. A deeper understanding of osteogenesis and angiogenesis has been hampered by technical difficulties of analyzing bone and neovasculature simultaneously in spatiotemporal scales and in 3D formats. To overcome these barriers, a cranial defect window chamber model was established that enabled high-resolution, longitudinal, and real-time tracking of angiogenesis and bone defect healing via multiphoton laser scanning microscopy (MPLSM). By simultaneously probing new bone matrix via second harmonic generation (SHG), neovascular networks via intravenous perfusion of fluorophore, and osteoblast differentiation via 2.3-kb collagen type I promoter-driven GFP (Col2.3GFP), we examined the morphogenetic sequence of cranial bone defect healing and further established the spatiotemporal analyses of osteogenesis and angiogenesis coupling in repair and regeneration. We showed that bone defect closure was initiated in the residual bone around the edge of the defect. The expansion and migration of osteoprogenitors into the bone defect occurred during the first 3 weeks of healing, coupled with vigorous microvessel angiogenesis at the leading edge of the defect. Subsequent bone repair was marked by matrix deposition and active vascular network remodeling within new bone. Implantation of bone marrow stromal cells (BMSCs) isolated from Col2.3GFP mice further showed that donor-dependent bone formation occurred rapidly within the first 3 weeks of implantation, in concert with early angiogenesis. The subsequent bone wound closure was largely host-dependent, associated with localized modest induction of angiogenesis. The establishment of a live imaging platform via cranial window provides a unique tool to understand osteogenesis and angiogenesis in repair and regeneration, enabling further elucidation of the spatiotemporal regulatory mechanisms of osteoprogenitor cell interactions with host bone healing microenvironment.


Assuntos
Imageamento Tridimensional/métodos , Neovascularização Fisiológica , Osteogênese , Crânio/patologia , Cicatrização , Animais , Agregação Celular , Sistemas Computacionais , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos Transgênicos , Microscopia Confocal , Nestina/metabolismo , Osteoblastos/metabolismo , Regeneração , Análise Espaço-Temporal
19.
Lab Chip ; 15(3): 735-44, 2015 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-25428803

RESUMO

In recognition of the limitations of monolayer cell cultures and resource-intensive animal studies, a microfluidic culture system was developed for creation of physiologically relevant three-dimensional (3D) tissues. In this study, an in vitro 3D breast cancer tissue model was established in a microfluidic system with human breast cancer cells (MCF-7) and primary adipose-derived stromal cells (ASCs). It was evaluated for utility in determining the efficiency of photodynamic therapy (PDT) with therapeutic agents (i.e. photosensitizer and gold nanoparticles) under various irradiation conditions. We demonstrated, for the first time, the potential use of a microfluidic-based in vitro 3D breast cancer model for effective evaluation of PDT, with the capability of controlling 3D microenvironments for breast cancer tissue formation, real-time monitoring of tissue progression, implementing a circulation-like dynamic medium flow and drug supplements, and investigating the relation between light penetration and tissue depth in PDT.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Técnicas Analíticas Microfluídicas , Modelos Biológicos , Fotoquimioterapia , Neoplasias da Mama/metabolismo , Sobrevivência Celular , Células Cultivadas , Desenho de Equipamento , Feminino , Humanos , Células MCF-7 , Técnicas Analíticas Microfluídicas/instrumentação , Espécies Reativas de Oxigênio/metabolismo
20.
Chem Commun (Camb) ; 50(56): 7548-51, 2014 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-24875274

RESUMO

Crystallization of a solution with high enantiomeric excess can generate a mixture of crystals of the desired enantiomer and the racemic compound. Using a mixture of S-/RS-ibuprofen crystals as a model, we demonstrated that magnetic levitation (MagLev) is a useful technique for analysis, separation and enantioenrichment of chiral/racemic products.


Assuntos
Técnicas de Química Analítica/métodos , Campos Magnéticos , Tamanho da Partícula , Cristalização , Fenômenos Magnéticos , Estereoisomerismo
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