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1.
Plant J ; 115(2): 529-545, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37029760

RESUMO

The plant secondary cell wall is a thickened matrix of polysaccharides and lignin deposited at the cessation of growth in some cells. It forms the majority of carbon in lignocellulosic biomass, and it is an abundant and renewable source for forage, fiber, materials, fuels, and bioproducts. The complex structure and arrangement of the cell wall polymers mean that the carbon is difficult to access in an economical and sustainable way. One solution is to alter the cell wall polymer structure so that it is more suited to downstream processing. However, it remains difficult to predict what the effects of this engineering will be on the assembly, architecture, and properties of the cell wall. Here, we make use of Arabidopsis plants expressing a suite of genes to increase pectic galactan chain length in the secondary cell wall. Using multi-dimensional solid-state nuclear magnetic resonance, we show that increasing galactan chain length enhances pectin-cellulose spatial contacts and increases cellulose crystallinity. We also found that the increased galactan content leads to fewer spatial contacts of cellulose with xyloglucan and the backbone of pectin. Hence, we propose that the elongated galactan side chains compete with xyloglucan and the pectic backbone for cellulose interactions. Due to the galactan topology, this may result in comparatively weak interactions and disrupt the cell wall architecture. Therefore, introduction of this strategy into trees or other bioenergy crops would benefit from cell-specific expression strategies to avoid negative effects on plant growth.


Assuntos
Arabidopsis , Celulose , Celulose/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Galactanos/metabolismo , Pectinas/metabolismo , Parede Celular/metabolismo , Carbono/metabolismo
2.
Breast Cancer Res ; 26(1): 99, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867302

RESUMO

In this study, we prepared a bionic nanosystem of trastuzumab-functionalized SK-BR-3 cell membrane hybrid liposome-coated pyrotinib (Ptb-M-Lip-Her) for the treatment of HER2-positive breast cancer. Transmission electron microscopy, dynamic light scattering, polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting were used to verify the successful preparation of Ptb-M-Lip-Her. In vitro drug release experiments proved that Ptb-M-Lip-Her had a sustained release effect. Cell uptake experiments and in vivo imaging experiments proved that Ptb-M-Lip-Her had good targeting ability to homologous tumor cells (SK-BR-3). The results of cell experiments such as MTT, flow cytometry, immunofluorescence staining and in vivo antitumor experiments showed that Ptb-M-Lip-Her could significantly promote apoptosis and inhibit the proliferation of SK-BR-3 cells. These results clearly indicated that Ptb-M-Lip-Her may be a promising biomimetic nanosystem for targeted therapy of HER2-positive breast cancer.


Assuntos
Apoptose , Neoplasias da Mama , Lipossomos , Receptor ErbB-2 , Trastuzumab , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Feminino , Lipossomos/química , Trastuzumab/administração & dosagem , Trastuzumab/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Animais , Linhagem Celular Tumoral , Camundongos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Sistemas de Liberação de Medicamentos , Terapia de Alvo Molecular , Acrilamidas , Aminoquinolinas
3.
J Nanobiotechnology ; 22(1): 547, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39238027

RESUMO

Rheumatoid arthritis (RA) involves chronic inflammation, oxidative stress, and complex immune cell interactions, leading to joint destruction. Traditional treatments are often limited by off-target effects and systemic toxicity. This study introduces a novel therapeutic approach using hyaluronic acid (HA)-conjugated, redox-responsive polyamino acid nanogels (HA-NG) to deliver tacrolimus (TAC) specifically to inflamed joints. The nanogels' disulfide bonds enable controlled TAC release in response to high intracellular glutathione (GSH) levels in activated macrophages, prevalent in RA-affected tissues. In vitro results demonstrated that HA-NG/TAC significantly reduced TAC toxicity to normal macrophages and showed high biocompatibility. In vivo, HA-NG/TAC accumulated more in inflamed joints compared to non-targeted NG/TAC, enhancing therapeutic efficacy and minimizing side effects. Therapeutic evaluation in collagen-induced arthritis (CIA) mice revealed HA-NG/TAC substantially reduced paw swelling, arthritis scores, synovial inflammation, and bone erosion while suppressing pro-inflammatory cytokine levels. These findings suggest that HA-NG/TAC represents a promising targeted drug delivery system for RA, offering potential for more effective and safer clinical applications.


Assuntos
Artrite Experimental , Artrite Reumatoide , Ácido Hialurônico , Nanogéis , Peptídeos , Tacrolimo , Animais , Ácido Hialurônico/química , Artrite Reumatoide/tratamento farmacológico , Camundongos , Tacrolimo/farmacologia , Tacrolimo/uso terapêutico , Tacrolimo/química , Tacrolimo/farmacocinética , Artrite Experimental/tratamento farmacológico , Peptídeos/química , Peptídeos/farmacologia , Nanogéis/química , Masculino , Células RAW 264.7 , Sistemas de Liberação de Medicamentos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos DBA , Portadores de Fármacos/química , Humanos
4.
J Liposome Res ; 34(3): 489-506, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38269490

RESUMO

Breast cancer stem cells (BCSCs) play a key role in therapeutic resistance in breast cancer treatments and disease recurrence. This study aimed to develop a combination therapy loaded with pH-sensitive liposomes to kill both BCSCs and the okbulk cancer cells using trastuzumab-sensitive and resistant human epidermal growth factor receptor 2 positive (HER2+) breast cancer cell models. The anti-BCSCs effect and cytotoxicity of all-trans retinoic acid, salinomycin, and bufalin alone or in combination with doxorubicin were compared in HER2+ cell line BT-474 and a validated trastuzumab-resistant cell line, BT-474R. The most potent anti-BCSC agent was selected and loaded into a pH-sensitive liposome system. The effects of the liposomal combination on BCSCs and bulk cancer cells were assessed. Compared with BT-474, the aldehyde dehydrogenase positive BCSC population was elevated in BT-474R (3.9 vs. 23.1%). Bufalin was the most potent agent and suppressed tumorigenesis of BCSCs by ∼50%, and showed strong synergism with doxorubicin in both BT-474 and BT-474R cell lines. The liposomal combination of bufalin and doxorubicin significantly reduced the BCSC population size by 85%, and inhibited both tumorigenesis and self-renewal, although it had little effect on the migration and invasiveness. The cytotoxicity against the bulk cancer cells was also enhanced by the liposomal combination than either formulation alone in both cell lines (p < 0.001). The liposomal bufalin and doxorubicin combination therapy may effectively target both BCSCs and bulk cancer cells for a better outcome in trastuzumab-resistant HER2+ breast cancer.


Assuntos
Neoplasias da Mama , Bufanolídeos , Doxorrubicina , Resistencia a Medicamentos Antineoplásicos , Lipossomos , Células-Tronco Neoplásicas , Trastuzumab , Humanos , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Bufanolídeos/farmacologia , Bufanolídeos/administração & dosagem , Bufanolídeos/química , Células-Tronco Neoplásicas/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Lipossomos/química , Feminino , Trastuzumab/farmacologia , Trastuzumab/administração & dosagem , Linhagem Celular Tumoral , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Receptor ErbB-2/metabolismo , Sobrevivência Celular/efeitos dos fármacos
5.
Dig Dis Sci ; 68(1): 138-146, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35451710

RESUMO

BACKGROUND AND AIMS: We have previously shown that gabexate mesylate-poloxamer 407 conjugate (GMTI) alleviates traumatic pancreatitis in rats. In this study, we evaluated the therapeutic effect of GMTI on sodium taurocholate-induced severe acute pancreatitis (SAP) in an optimized rat model. METHODS: An SAP rat model was established via microinjection of 3.5% sodium taurocholate and retention in the bile duct for 1 min. SAP rats were administered GMTI via tail vein injection (i.v.) or tail vein injection + intraperitoneal injection (i.v. + i.p.). All rats were sacrificed at 12 h after treatment. Biochemical approach and enzyme-linked immunosorbent assay were performed to measure the serum levels of amylase (AMY), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Hematoxylin and eosin staining and TUNEL assay were conducted to examine histopathology and acinar cell apoptosis in the rat pancreas. RESULTS: SAP was successfully induced in all model rats, as evidenced by progressively aggravating SAP symptoms and signs, pancreatic histopathological abnormalities, as well as elevated serum levels of TNF-α, IL-6, and AMY. The mortality rates at 1 h, 6 h, and 12 h were 0%, 0%, and 25%, respectively. GMTI therapy via i.v. or i.v. + i.p. significantly reduced pancreatic wet weights, ascites amounts, pathological scores, and circulating levels of TNF-α and IL-6 while promoting acinar cell apoptosis in SAP rats. GMTI therapy via i.v. + i.p. outperformed i.v. in improving pancreatic histology and reducing TNF-α and IL-6 serum levels in SAP rats. CONCLUSIONS: Our optimized SAP rat model is reliable and reproducible. GMTI therapy is a promising approach against SAP.


Assuntos
Gabexato , Pancreatite , Ratos , Animais , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Pancreatite/patologia , Gabexato/efeitos adversos , Poloxâmero/farmacologia , Interleucina-6 , Fator de Necrose Tumoral alfa , Ratos Sprague-Dawley , Ácido Taurocólico , Doença Aguda , Pâncreas/patologia
6.
Biomacromolecules ; 23(6): 2197-2218, 2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35522524

RESUMO

Cancer is a worldwide public health issue that has not been conquered. Theranostics, the combination of a therapeutic drug and imaging agent in one formulation using nanomaterials, has been developed to better cure cancer in recent years. Although diverse biomaterials have been applied in cancer theranostics, chitosan (CS), a natural polysaccharide bearing easy modification sites with excellent biocompatibility and biodegradability, shows great potential for developing cancer nanotheranostics. In this review, we seek to describe the chemical functionalities of CS used in cancer theranostics and their synthesis methods. We also present recent discoveries and research progresses on how the CS functionalization could improve the delivery efficiency of CS-based nanotheranostics. Finally, we report several case studies about the application of CS-based nanotheranostics. This paper focuses on the strategies to construct CS-based theranostics systems via chemical routes and highlights their applications in cancer treatment, which can provide useful references for further studies.


Assuntos
Quitosana , Nanoestruturas , Neoplasias , Materiais Biocompatíveis/uso terapêutico , Quitosana/uso terapêutico , Humanos , Nanoestruturas/uso terapêutico , Neoplasias/tratamento farmacológico , Nanomedicina Teranóstica/métodos
7.
BMC Biotechnol ; 21(1): 5, 2021 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-33422076

RESUMO

BACKGROUND: At present, microorganism has been considered as important factors that threaten to buried pipelines with disbonded coatings. Aiming at the problem of unknown corrosion mechanism of sulfate-reducing bacteria (SRB), a series of studies have been carried out in this paper. Spectrophotometer and fluorescent labeling technology are used to study the growth and attachment of SRB in the simulated soil solution. The corrosion behavior of X80 pipeline steel with or without SRB was researched by electrochemical methods such as open circuit potential, dynamic potential polarization curve, and electrochemical impedance spectroscopy. The microscopic morphology of the corrosion products on the surface was observed with a scanning electron microscope (SEM), and the element content of the corrosion products on the surface of the sample after corrosion was observed using X-ray energy spectrum (EDS) analysis. RESULTS: The results showed that the growth and reproduction of SRB caused the pH of the soil simulated solution to increase, which may promote the corrosion of X80 steel. In addition, the cathode reaction of X80 steel in a sterile environment is the reduction of H+, and the main corrosion product is iron oxide. When the soil simulation solution contains SRB, the cathodic reaction is controlled by both H+ reduction and sulfide depolarization reactions, and FeS appears in the corrosion products. CONCLUSION: Although the life cycle of SRB is only about 14 days, the corrosion of X80 steel is greatly promoted by SRB, and even causes corrosion perforation, which will bring huge economic losses and serious safety hazards.


Assuntos
Bactérias/metabolismo , Aço/química , Sulfatos/metabolismo , Corrosão , Técnicas Eletroquímicas , Eletroquímica , Compostos Férricos , Solo , Microbiologia do Solo
8.
J Nanobiotechnology ; 19(1): 151, 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34022897

RESUMO

BACKGROUD: Colon cancer contributes to high mortality rates as the result of incomplete resection in tumor surgery. Multimodal imaging can provide preoperative evaluation and intraoperative image-guiding. As biocompatible nanocarriers, extracellular vesicles hold great promise for multimodal imaging. In this study, we aim to synthesized an extracellular vesicles-based nanoprobe to visualize colon cancer with positron-emission tomography/computed tomography (PET/CT) and near-infrared fluorescence (NIRF) imaging, and investigated its utility in image-guided surgery of colon cancer in animal models. RESULTS: Extracellular vesicles were successfully isolated from adipose-derived stem cells (ADSCs), and their membrane vesicles were observed under TEM. DLS detected that the hydrodynamic diameters of the extracellular vesicles were approximately 140 nm and the zeta potential was - 7.93 ± 0.24 mV. Confocal microscopy showed that extracellular vesicles had a strong binding ability to tumor cells. A click chemistry-based pre-targeting strategy was used to achieve PET imaging in vivo. PET images and the biodistribution results showed that the best pre-targeting time was 20 h, and the best imaging time was 2 h after the injection of 68 Ga-L-NETA-DBCO. The NIRF images showed that the tumor had clear images at all time points after administration of nanoparticles and the Tumor/Muscle ratio peaked at 20 h after injection. Our data also showed that both PET/CT and NIRF imaging clearly visualized the orthotopic colon cancer models, providing preoperative evaluation. Under real-time NIRF imaging, the tumor location and tumor boundary could be clearly observed. CONCLUSIONS: In brief, this novel nanoprobe may be useful for multi-modal imaging of colon cancer and NIRF image-guided surgery. More importantly, this study provides a new possibility for clinical application of extracellular vesicles as nanocarriers.


Assuntos
Neoplasias do Colo/diagnóstico por imagem , Vesículas Extracelulares , Imagem Multimodal/métodos , Cirurgia Assistida por Computador/métodos , Animais , Materiais Biocompatíveis , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Fluorescência , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanoestruturas , Imagem Óptica/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Distribuição Tecidual
9.
Arch Environ Contam Toxicol ; 81(1): 155-165, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34043040

RESUMO

In this study, three different types of microplastics were aged by the thermal activation K2S2O8 method to investigate the adsorption behavior for sulfamethoxazole (SMX) in aqueous solution. The effects of pH, salinity and humic acid (HA) on adsorption behavior were also investigated. At the same time, the morphology and functional groups of microplastics before and after adsorption were characterized. As the aging time increased, the adsorption capacity of the microplastics also increased significantly. Whether it was pristine or aged, polylactic acid (PLA) had the highest adsorption capacity. The adsorption capacity of microplastics was the largest under acidic conditions, and its adsorption capacity decreased significantly in alkaline solutions. The presence of salinity inhibited the adsorption of SMX on polyethylene terephthalate (PET) and PP, but the adsorption capacity of PLA increases when salinity was above 10‰. The adsorption of SMX on microplastics was promoted by HA. When the concentration of HA was 20 mg/L, the adsorption capacity of PLA and PET decreased. Kinetic and isotherm fits were applied to the adsorption process. The increase in sorption capacity was related to the development of holes and cracks and the enhanced number of surface oxygen-containing functional groups. The adsorption kinetics to pristine microplastics conformed to a pseudo-first-order kinetic model, while the kinetics of the aged microplastics conformed to a pseudo-second-order kinetic model. It implies that the adsorption of SMX by aging microplastics involves multiple processes. The adsorption isothermal adsorption process of SMX by microplastics accorded with Freundlich model, belonging to multi-layer adsorption.


Assuntos
Microplásticos , Poluentes Químicos da Água , Adsorção , Cinética , Plásticos , Sulfametoxazol , Poluentes Químicos da Água/análise
10.
Ecotoxicol Environ Saf ; 190: 110151, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31923754

RESUMO

Potentially toxic metals (PTMs), associated with different size particles in soil, may play an important role in adverse health effect and risk for human. The objective is to evaluate the lung and gastrointestinal bioaccessibility and risk of PTMs in Pb-contaminated alkaline urban soil depending on the particle size fractions. The size fractions of 50-250 µm, 5-50 µm, 1-5 µm, <1 µm in Pb-contaminated alkaline urban soil from Baoji Heavy Industrial Base City, NW China, were screened by Sequential Wet Sieving Separation Procedure (SWSSP) based on Stokes' Law. The concentrations of 9 potentially toxic metals (As, Ba, Co, Cr, Cu, Mn, Ni, Pb and Zn) in each particle size fractions were characterized by ICP-OES and ICP-MS, and the in vitro bioaccessibility dependent of size fractions were evaluated by the simulation fluids of Artificial Lysosomal Fluid (ALF) and Gamble for lung, PBET, SBET, IVG, SBRC, UBM for gastric and intestinal, respectively. Health risks were assessed considering simulated external exposure using intestinal and lung bioaccessibility. The lung and gastrointestinal bioaccessibility and exposure risks of PTMs in fine particle size (i.e. <1 µm) was higher than larger particle size fractions (i.e. 50-250 µm, 5-50 µm, 1-5 µm), however, some different variations of bioaccessibility observed the simulation fluids and time dependent. In case of single PTMs, the lung bioaccessibilities of PTMs in ALF were higher than those in Gamble fluids, most prominent in Co, Cu, Mn and Zn, while the gastrointestinal [G + I] bioaccessibility of PTMs was less than those in gastric [G], like Cu, Mn, Pb and Zn mostly. The non-carcinogenic risks of these PTMs to children via inhalation were acceptable and higher than those of adults, but reverse for carcinogenic risk. Comparatively, the non-carcinogenic and carcinogenic risks of PTMs via ingestion pathway were both higher than those for adults. Although the risks from ingestion were in acceptable range, the total carcinogenic risks for children were more than 10-4, which would bring carcinogenic risks and should be paid attention to. It was noted that the toxic metal, Co in all size fractions was the most important contributor for noncarcinogenic risks and Cr mostly for carcinogenic risks via inhalation pathway for adults and children in local areas. However, Pb was the most important contributor for noncarcinogenic risk both for adults and children via ingestion pathway relative to Co and Cr for carcinogenic risks through hand-to-mouth ingestion. Those observations demonstrated the important role that the smaller particle fractionations in Pb-contaminated alkaline soil played in both bioaccessibility and the refinement of human health-risk assessments for the inhalation and ingestion pathway.


Assuntos
Arsênio/metabolismo , Trato Gastrointestinal/metabolismo , Pulmão/metabolismo , Metais Pesados/metabolismo , Tamanho da Partícula , Poluentes do Solo/metabolismo , Adulto , Arsênio/química , Disponibilidade Biológica , Criança , China , Cidades , Humanos , Metais Pesados/química , Modelos Biológicos , Medição de Risco/métodos , Poluentes do Solo/química
11.
J Am Chem Soc ; 141(10): 4406-4411, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30801185

RESUMO

The precise and highly efficient drug delivery of nanomedicines into lesions remains a critical challenge in clinical translational research. Here, an autocatalytic morphology transformation platform is presented for improving the tumor-specific accumulation of drugs by kinetic control. The in situ reorganization of prodrug from nanoparticle to ß-sheet fibrous structures for targeted accumulation is based on nucleation-based growth kinetics. During multiple administrations, the autocatalytic morphology transformation can be realized for skipping slow nucleating process and constructing the bulky nanoassembly instantaneously, which has been demonstrated to induce the cumulative effect of prodrug. Furthermore, the sustained drug release from fibrous prodrug depot in the tumor site inhibits the tumor growth efficiently. The autocatalytic morphology transformation strategy in vivo offers a novel perspective for targeted delivery strategy by introducing chemical kinetics and shows great potential in disease theranostics.


Assuntos
Antineoplásicos/farmacologia , Camptotecina/farmacologia , Portadores de Fármacos/química , Nanofibras/química , Peptídeos/química , Animais , Antineoplásicos/metabolismo , Camptotecina/análogos & derivados , Camptotecina/metabolismo , Catepsina B/metabolismo , Preparações de Ação Retardada , Portadores de Fármacos/metabolismo , Liberação Controlada de Fármacos , Feminino , Células HeLa , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/metabolismo , Peptídeos/metabolismo , Polietilenoglicóis/química , Pró-Fármacos/química , Pró-Fármacos/metabolismo , Multimerização Proteica , Proteólise
12.
J Am Chem Soc ; 141(18): 7235-7239, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-31010287

RESUMO

The morphology controlled molecular assemblies play vital roles in biological systems. Here we present endogenous reactive oxygen species (ROS)-triggered morphology transformation of polymer-peptide conjugates (PPCs) for cooperative interaction with mitochondria, exhibiting high tumor therapeutic efficacy. The PPCs are composed of (i) a ß-sheet-forming peptide KLVFF conjugated with poly(ethylene glycol) through ROS-cleavable thioketal, (ii) a mitochondria-targeting cytotoxic peptide KLAK, and (iii) a poly(vinyl alcohol) backbone. The self-assembled PPCs nanoparticles can enter cells and target mitochondria. Because of overgenerated ROS around mitochondria in most cancer cells, the thioketal linker can be cleaved, leading to transformation from nanoparticles to fibrous nanostructures. As a result, the locational nanofibers with exposure of KLAK exhibit enhanced multivalent cooperative interactions with mitochondria, which causes selective cytotoxicity against cancer cells and powerful tumor suppression efficacy in vivo. As the first example of ROS-triggered intracellular transformation, the locational assembly strategy in vivo may provide a new insight for disease diagnosis and therapy through enhanced interaction with targeting site.


Assuntos
Antineoplásicos/metabolismo , Mitocôndrias/metabolismo , Peptídeos/metabolismo , Álcool de Polivinil/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Camundongos , Mitocôndrias/química , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Imagem Óptica , Peptídeos/química , Peptídeos/farmacologia , Álcool de Polivinil/química , Álcool de Polivinil/farmacologia , Espécies Reativas de Oxigênio/química
13.
Molecules ; 24(1)2019 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-30621128

RESUMO

Enzyme-aid maceration is carried out in most modern winemaking industries with a range of positive impacts on wine production. However, inconsistencies in enzyme efficiency are an issue complicated by unclear targets (limited information available on berry cell wall architecture of different cultivars) and the complex wine environment (i.e., fermenting must). Recent studies have been performed to develop a clearer picture of grape cell wall structures, maceration effects, and interactions between important wine compounds and grape-derived polysaccharides. This review highlights critically important recent studies on grape berry cell wall changes during ripening, the importance of enzymes during maceration (skin contact phase) and deconstruction processes that occur during alcoholic fermentation. The novelty of the Comprehensive Microarray Polymer Profiling (CoMPP) technique using cell wall probes (e.g., antibodies) as a method for following cell wall derived polymers during different biological and biotechnological processes is discussed. Recent studies, using CoMPP together with classical analytical methods, confirmed the developmental pattern of berry cell wall changes (at the polymer level) during grape ripening. This innovative technique were also used to track enzyme-assisted depectination of grape skins during wine fermentation and determine how this influence the release of wine favourable compounds. Furthermore, polysaccharides (e.g., arabinogalactan proteins) present in the final wine could be identified. Overall, CoMPP provides a much more enriched series of datasets compared to traditional approaches. Novel insights and future studies investigating grape cell wall and polyphenol interactions, and the tailoring of enzyme cocktails for consistent, effective and "customized" winemaking is advanced and discussed.


Assuntos
Parede Celular/química , Polissacarídeos/química , Vitis , Vinho , Parede Celular/genética , Fermentação , Análise em Microsséries , Mucoproteínas/química , Proteínas de Plantas/química , Polímeros/química , Polissacarídeos/genética
14.
Angew Chem Int Ed Engl ; 58(14): 4632-4637, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30695128

RESUMO

In cancer treatment, the unsatisfactory solid-tumor penetration of nanomaterials limits their therapeutic efficacy. We employed an in vivo self-assembly strategy and designed polymer-peptide conjugates (PPCs) that underwent an acid-induced hydrophobicity increase with a narrow pH-response range (from 7.4 to 6.5). In situ self-assembly in the tumor microenvironment at appropriate molecular concentrations (around the IC50 values of PPCs) enabled drug delivery deeper into the tumor. A cytotoxic peptide KLAK, decorated with the pH-sensitive moiety cis-aconitic anhydride (CAA), and a cell-penetrating peptide TAT were conjugated onto poly(ß-thioester) backbones to produce PT-K-CAA, which can penetrate deeply into solid tumors owing to its small size as a single chain. During penetration in vivo, CAA responds to the weak acid, leading to the self-assembly of PPCs and the recovery of therapeutic activity. Therefore, a deep-penetration ability for enhanced cancer therapy is provided by this in vivo assembly strategy.


Assuntos
Antineoplásicos/farmacologia , Peptídeos/farmacologia , Polímeros/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Ácido Aconítico/administração & dosagem , Ácido Aconítico/análogos & derivados , Ácido Aconítico/química , Ácido Aconítico/farmacologia , Administração Intravenosa , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Tamanho da Partícula , Peptídeos/administração & dosagem , Peptídeos/química , Polímeros/administração & dosagem , Polímeros/química , Propriedades de Superfície
15.
J Surg Res ; 228: 93-99, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29907236

RESUMO

BACKGROUND: Although peritoneal lavage with povidone-iodine (PVPI) is frequently performed after surgery on the gastrointestinal tract, the effects of PVPI on the intestinal epithelial barrier are unknown. The purpose of this study was to investigate the effects of abdominal irrigation with PVPI on the intestinal epithelial barrier in a colorectal cancer (CRC)-induced rat model. MATERIALS AND METHODS: The CRC model was induced in rats with azoxymethane and dextran sodium sulfate. Next, a total of 24 male CRC-induced rats were randomly divided into three groups (n = 8): (1) a sham-operated group, (2) an NS group (peritoneal lavage 0.9% NaCl), and (3) a PVPI group (peritoneal lavage with 0.45%-0.55% PVPI). The mean arterial pressure was continuously monitored throughout the experiment. The levels of plasma endotoxin and D-lactate, blood gases, and protein concentration were measured. The ultrastructural changes of the epithelial tight junctions were observed by transmission electron microscopy. RESULTS: The mean arterial pressure after peritoneal lavage was lower in the PVPI group than that in the NS group. The protein concentration and levels of endotoxin and D-lactate were higher in the PVPI group than they were in the PVPI group. In addition, PVPI treatment resulted in a markedly severe metabolic acidosis and intestinal mucosal injury compared with NS rats. CONCLUSIONS: Peritoneal lavage with PVPI dramatically compromises the integrity of the intestinal mucosa barrier and causes endotoxin shock in CRC rats. It is unsafe for clinical applications to include peritoneal lavage with PVPI in colorectal operations.


Assuntos
Anti-Infecciosos Locais/efeitos adversos , Neoplasias Colorretais/cirurgia , Lavagem Peritoneal/efeitos adversos , Povidona-Iodo/efeitos adversos , Choque Séptico/induzido quimicamente , Acidose/induzido quimicamente , Acidose/diagnóstico , Animais , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/farmacocinética , Azoximetano/toxicidade , Translocação Bacteriana/efeitos dos fármacos , Neoplasias Colorretais/induzido quimicamente , Sulfato de Dextrana/toxicidade , Endotoxinas/sangue , Endotoxinas/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Masculino , Microscopia Eletrônica de Transmissão , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/cirurgia , Absorção Peritoneal , Lavagem Peritoneal/métodos , Permeabilidade/efeitos dos fármacos , Povidona-Iodo/administração & dosagem , Povidona-Iodo/farmacocinética , Ratos , Ratos Sprague-Dawley , Choque Séptico/sangue , Choque Séptico/diagnóstico , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/ultraestrutura
16.
Bioorg Med Chem Lett ; 28(18): 3119-3122, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30119959

RESUMO

Oxidative stress has been regarded as the leading mechanism of the hepatotoxicity of clofibrate (CF). To achieve multifunctional novel hypolipidemic agents with hypolipidemia, antioxidant, and ameliorating liver injury, clofibric acid derivative hydroxytyrosol-clofibrate (CF-HT) was synthesized by molecular hybridization. CF-HT exhibited significant hypolipidemia, reducing serum triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 30%, 33%, and 29% in hyperlipidemic mice induced by Triton WR 1339. CF-HT also shown hepatoprotective effect, a significant decrease in hepatic indices toxicity was observed, i.e. aspartate and lactate transaminases (AST and ALT) activities, alkalines phosphatases (ALP), and total bilirubin (TBIL) levels. The liver weight and liver coefficient were also ameliorated. Serum superoxide dismutase (SOD) was significantly elevated, and serum catalase (CAT) and malondialdehyde (MDA) content were remarkably restored. The hepatic glutathione (GSH) content was obviously increased and hepatic oxidized glutathione (GSSG) content was reduced dramatically by CF-HT, as compared to the CF treated mice (p < 0.05). Moreover, the histopathological damage that hepatocyte hyperplasia and hypertrophy was also significantly ameliorated by treatment with CF-HT. Therefore, the results indicated that CF-HT exerted more potent hypolipidemic activity and definite hepatoprotective effect which may mainly be associated with its antioxidative property in mice.


Assuntos
Antioxidantes/farmacologia , Clofibrato/farmacologia , Hepatócitos/efeitos dos fármacos , Hipolipemiantes/farmacologia , Álcool Feniletílico/análogos & derivados , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Peso Corporal/efeitos dos fármacos , Clofibrato/administração & dosagem , Clofibrato/química , Relação Dose-Resposta a Droga , Hepatócitos/metabolismo , Hipolipemiantes/administração & dosagem , Hipolipemiantes/química , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estrutura Molecular , Tamanho do Órgão/efeitos dos fármacos , Álcool Feniletílico/administração & dosagem , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia , Polietilenoglicóis/farmacologia , Relação Estrutura-Atividade
17.
BMC Vet Res ; 14(1): 359, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30458768

RESUMO

BACKGROUND: Foot-and-mouth disease (FMD) caused by foot-and-mouth disease virus (FMDV) is one of the most highly infectious diseases in livestock, and leads to huge economic losses. Early diagnosis and rapid differentiation of FMDV serotype is therefore integral to the prevention and control of FMD. In this study, a series of serotype-specific reverse transcription recombinase polymerase amplification assays combined with lateral flow dipstick (RPA-LFD) were establish to differentiate FMDV serotypes A, O or Asia 1, respectively. RESULTS: The serotype-specific primers and probes of RPA-LFD were designed to target conserved regions of the FMDV VP1 gene sequence, and three primer and probe sets of serotype-specific RPA-LFD were selected for amplification of FMDV serotypes A, O or Asia 1, respectively. Following incubation at 38 °C for 20 min, the RPA amplification products could be visualized by LFD. Analytical sensitivity of the RPA assay was then determined with ten-fold serial dilutions of RNA of VP1 gene and the recombinant vector respectively containing VP1 gene from FMDV serotypes A, O or Asia1, the detection limits of these assays were 3 copies of plasmid DNA or 50 copies of viral RNA per reaction. Moreover, the specificity of the assay was assessed, and there was no cross reactions with other viruses leading to bovine vesicular lesions. Furthermore, 126 clinical samples were respectively detected with RPA-LFD and real-time PCR (rPCR), there was 98.41% concordance between the two assays, and two samples were positive by RPA-LFD but negative in rPCR, these were confirmed as FMDV-positive through viral isolation in BHK-21 cells. It showed that RPA-LFD assay was more sensitive than the rPCR method in this study. CONCLUSION: The development of serotype-specific RPA-LFD assay provides a rapid, sensitive, and specific method for differentiation of FMDV serotype A, O or Asia1, respectively. It is possible that the serotype-specific RPA-LFD assay may be used as a integral protocol for field detection of FMDV.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa/diagnóstico , Técnicas de Amplificação de Ácido Nucleico/veterinária , Sorotipagem/veterinária , Animais , Bovinos/virologia , Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/virologia , Vírus da Febre Aftosa/classificação , Vírus da Febre Aftosa/genética , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/veterinária , Técnicas de Amplificação de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Sensibilidade e Especificidade , Sorotipagem/métodos
18.
Int J Mol Sci ; 19(10)2018 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-30241343

RESUMO

In this study, the adsorption of lignin-modified silica gel after association with six different organophenylmercuric compounds in chloroform was investigated. Adsorption reached approximately 90% of the maximum value within 15 min. The adsorption capacity, Fourier transform infrared spectroscopy, and interaction simulation results indicated that the adsorption proportion resulted from the strong dipole-dipole interaction between the lignin and analyte molecules, and was considered to be size- and structure-dependent. However, the π-π complexation interaction arising from the acidic aromatic moiety of the analyte, which was significant in an apolar environment, was not the major force responsible for the resulting adsorption. Additives, such as acid or ether, which competed with the analyte for the binding site on the lignin molecule, were not beneficial to the interaction, and thus not beneficial to the adsorption processes.


Assuntos
Lignina/química , Compostos Organomercúricos/química , Sílica Gel/química , Adsorção , Sítios de Ligação , Clorofórmio/química , Modelos Moleculares , Espectroscopia de Infravermelho com Transformada de Fourier
19.
Plant Cell Physiol ; 63(6): 734-736, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35413114
20.
Zhongguo Zhong Yao Za Zhi ; 42(10): 1957-1963, 2017 May.
Artigo em Zh | MEDLINE | ID: mdl-29090557

RESUMO

The experiment was aimed to investigate the difference of plasma concentration and pharmacokinetic parameters between liposome and aqueous solution of toatal ginsenoside of ginseng stems and leaves in rats, such as ginsenosides Rg1, Re, Rf, Rb1, Rg2, Rc, Rb2, Rb3, Rd. After intravenous injection of liposome and aqueous solution in rats, the blood was taken from the femoral vein to detect the plasma concentration of the above 9 ginsenoside monomers in different time points by using HPLC. The concentration-time curve was obtained and 3p97 pharmacokinetic software was used to get the pharmacokinetic parameters. After the intravenous injection of ginsenosides to rats, nine ginsenosides were detected in plasma. In general, among these ginsenosides, the peak time of the aqueous solution was between 0.05 to 0.083 3 h, and the serum concentration peak of liposome usually appeared after 0.5 h. After software fitting, the aqueous solution of ginsenoside monomers Rg1, Re, Rf, Rg2, Rc, Rd, Rb3 was two-compartment model, and the liposomes were one-compartment model; aqueous solution and liposome of ginsenoside monomers Rb1 were three-compartment model; aqueous solution of ginsenoside monomers Rb2 was three-compartment model, and its liposome was one-compartment model. Area under the drug time curve (AUC) of these 9 kinds of saponin liposomes was larger than that of aqueous solution, and the retention time of the liposomes was longer than that of the aqueous solution; the removal rate was slower than that of the aqueous solution, and the half-life was longer than that of the water solution. The results from the experiment showed that by intravenous administration, the pharmacokinetic parameters of two formulations were significantly different from each other; the liposomes could not only remain the drug for a longer time in vivo, but also reduce the elimination rate and increase the treatment efficacy. As compared with the traditional dosage forms, the total ginsenoside of ginseng stems and leaves can improve the sustained release of the drug, which is of great significance for the research and development of new dosage forms of ginsenosides in the future.


Assuntos
Ginsenosídeos/sangue , Ginsenosídeos/farmacocinética , Panax/química , Animais , Cromatografia Líquida de Alta Pressão , Lipossomos , Folhas de Planta/química , Caules de Planta/química , Ratos
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