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1.
Int J Biol Macromol ; 264(Pt 1): 130543, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38432271

RESUMO

Hydrogel microbeads can be used to enhance the stability of probiotics during gastrointestinal delivery and storage. In this study, the pectin-alginate hydrogel was enhanced by adding montmorillonite filler to produce microbeads for encapsulating Lactobacillus kefiranofaciens (LK). Results showed that the viscosity of biopolymer solutions with 1 % (PAMT1) and 3 % (PAMT3) montmorillonite addition was suitable for producing regular-shaped microbeads. A layered cross-linked network was formed on the surface of PAMT3 microbeads through electrostatic interaction between pectin-alginate and montmorillonite filler, and the surrounding LK with adsorbed montmorillonite was encapsulated inside the microbeads. PAMT3 microbeads reduced the loss of viability of LK when passing through the gastric acid environment, and facilitated the slow release of LK in the intestine and colonic colonization. The maximum decrease in viability among all filler groups was 1.21 log CFU/g after two weeks of storage, while PAMT3 freeze-drying microbeads only decreased by 0.46 log CFU/g, indicating that the gel layer synergized with the adsorbed layer to provide dual protection for probiotics. Therefore, filler-reinforced microbeads are a promising bulk encapsulation carrier with great potential for the protection and delivery of probiotics and can be developed as food additives for dairy products.


Assuntos
Alginatos , Lactobacillus , Probióticos , Pectinas , Bentonita , Microesferas , Hidrogéis , Viabilidade Microbiana
2.
Int J Biol Macromol ; 255: 128189, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37979766

RESUMO

Delivering drugs selectively to tumor tissues is a significant challenge in cancer therapy, and pH-responsive polymeric assemblies have shown great potential in achieving this goal. In this study, we developed a pH-responsive alginate-based assemblies, called (amine-modified ZnO)-oxidized alginate-PEG ((ZnO-N)-OAl-PEG), for selective drug delivery in cancer treatment. The incorporation of ZnO-N nanoparticles into the alginate-based assemblies enables pH-responsiveness and maintains stability under physiological conditions. At an acidic pH, (ZnO-N)-OAl-PEG disassembles due to the conversion of ZnO to Zn2+, which triggers the unloading of doxorubicin (DOX) from the imine bond between DOX and alginate. This unloading results in the death of cancer cells and inhibition of tumor growth. The anticancer efficacy of (DOX/ZnO-N)-OAl-PEG was demonstrated in vitro and in vivo, providing promising prospects for cancer treatment based on ZnO-induced pH-responsiveness. These findings may also inspire the development of advanced drug delivery systems (DDSs) for cancer therapy.


Assuntos
Nanopartículas , Neoplasias , Óxido de Zinco , Humanos , Óxido de Zinco/química , Alginatos , Sistemas de Liberação de Medicamentos/métodos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Doxorrubicina/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Concentração de Íons de Hidrogênio , Portadores de Fármacos/química , Linhagem Celular Tumoral
3.
Int J Biol Macromol ; 253(Pt 5): 127226, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37802455

RESUMO

Minimally processed fruits and vegetables (MPFVs) are gaining popularity in households because of their freshness, convenience, and rapid consumption, all of which align with today's busy lifestyles. However, their exposure of large surface areas during peeling and slicing can result in contamination by foodborne pathogens and spoilage bacteria, posing potential food safety concerns. In addition, enzymatic browning of MPFVs can significantly reduce their consumer appeal. Therefore, it is necessary to adopt certain methods to protect MPFVs. Recent studies have shown that utilizing biopolymer-based edible films containing probiotics is a promising approach to preserving MPFVs. These active food packaging films exhibit barrier function, antioxidant function, and antimicrobial function while protecting the viability of probiotics, which is essential to maintain the nutritional value and quality of MPFVs. This paper reviews microbial contamination in MPFVs and the preparation of probiotic-loaded edible films with common polysaccharides (alginate, gellan gum, and starch), proteins (zein, gelatin, and whey protein isolate), prebiotics (oligofructose, inulin, and fructooligosaccharides). It also explores the potential application of probiotic-loaded biopolymer films/coatings on MPFVs, and finally examines the practical application requirements from a consumer perspective.


Assuntos
Filmes Comestíveis , Probióticos , Prebióticos , Frutas/microbiologia , Verduras , Conservação de Alimentos/métodos , Embalagem de Alimentos/métodos , Proteínas , Amido
4.
Food Chem Toxicol ; 174: 113645, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36736610

RESUMO

Winter jujube (Ziziphus jujuba Mill. cv. Dongzao) is a major fresh-eating jujube fruit with various important nutrients for humans. It can absorb heavy metals from polluted air, water and soils and applied pesticides, which may pose potential threats to consumers. Here, to evaluate the content of heavy metals in winter jujube and systematically evaluate the potential risks, we collected 212 winter jujube samples from four main producing areas in China and determined the contents of eight heavy metals (Cd, Cr, Pb, Ni, Cu, Zn, As, and Mn) using inductively coupled plasma mass spectrometer (ICP-MS). Based on the integrated pollution index (IPI) evaluation standard, more than 99.06% of samples were at safe levels. Moreover, clustering analysis divided the eight heavy metals into four groups, namely Cr/Ni, Cd/Pb, Cu/Mn/Zn, and As. Importantly, none of the analyzed heavy metals posed risks to adults as indicted by the average carcinogenic and non-carcinogenic risks. Notably, Cr and Cd could pose low carcinogenic risks to children (≤12 age group) when their concentration reached the 90th percentile. This study systematically assessed the health risks associated with heavy metal intake through winter jujube consumption and highlighted the necessity of constant heavy metal monitoring in winter jujube.


Assuntos
Metais Pesados , Poluentes do Solo , Ziziphus , Adulto , Criança , Humanos , Cádmio/análise , Chumbo/análise , Monitoramento Ambiental , Metais Pesados/análise , China , Medição de Risco , Poluentes do Solo/análise
5.
Transgenic Res ; 32(1-2): 143-152, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36637628

RESUMO

The mouse Agouti gene encodes a paracrine signaling factor which promotes melanocytes to produce yellow instead of black pigment. It has been reported that Agouti mRNA is confined to the dermal papilla after birth in various mammalian species. In this study, we created and characterized a knockin mouse strain in which Cre recombinase was expressed in-frame with endogenous Agouti coding sequence. The Agouti-Cre mice were bred with reporter mice (Rosa26-tdTomato or Rosa26-ZsGreen) to trace the lineage of Agouti-expressing cells during development. In skin, the reporter was detected in some dermal fibroblasts at the embryonic stage and in all dermal fibroblasts postnatally. It was also expressed in all mesenchymal lineage cells in other organs/tissues, including eyes, tongue, muscle, intestine, adipose, prostate and testis. Interestingly, the reporter expression was excluded from epithelial cells in the above organs/tissues. In brain, the reporter was observed in the outermost meningeal fibroblasts. Our work helps to illustrate the Agouti expression pattern during development and provides a valuable mouse strain for conditional gene targeting in mesenchymal lineage cells in multiple organs.


Assuntos
Proteína Agouti Sinalizadora , Animais , Masculino , Camundongos , Marcação de Genes , Integrases/genética , Integrases/metabolismo , Camundongos Transgênicos , Proteína Agouti Sinalizadora/genética
6.
Dev Dyn ; 252(4): 527-535, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36576725

RESUMO

BACKGROUND: Transcription factor lymphoid enhancer-binding factor 1 (LEF1) is a downstream mediator of the Wnt/ß-catenin signaling pathway. It is expressed in dermal papilla and surrounding cells in the hair follicle, promoting cell proliferation, and differentiation. RESULTS: Here, we report that LEF1 is also expressed all through the hair cycle in the terminal Schwann cells (TSCs), a component of the lanceolate complex located at the isthmus. The timing of LEF1 appearance at the isthmus coincides with that of hair follicle innervation. LEF1 is not found at the isthmus in the aberrant hair follicles in nude mice. Instead, LEF1 in TSCs is found in the de novo hair follicles reconstituted on nude mice by stem cells chamber graft assay. Cutaneous denervation experiment demonstrates that the LEF1 expression in TSCs is independent of nerve endings. At last, LEF1 expression in the interfollicular epidermis during the early stage of skin development is significantly suppressed in transgenic mice with T-cell factor 3 (TCF3) overexpression. CONCLUSION: We reveal the expression dynamics of LEF1 in skin during development and hair cycle. LEF1 expression in TSCs indicates that the LEF1/Wnt signal might help to establish a niche at the isthmus region for the lanceolate complex, the bulge stem cells and other neighboring cells.


Assuntos
Epiderme , Folículo Piloso , Fator 1 de Ligação ao Facilitador Linfoide , Animais , Camundongos , beta Catenina/metabolismo , Epiderme/metabolismo , Fator 1 de Ligação ao Facilitador Linfoide/genética , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Camundongos Nus , Camundongos Transgênicos , Células de Schwann
7.
Cytometry A ; 101(8): 675-681, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35524584

RESUMO

Dermal papilla (DP) cells regulate hair follicle epithelial cells and melanocytes by secreting functional factors, playing a key role in hair follicle morphogenesis and hair growth. DP cells can reconstitute new hair follicles and induce hair regeneration, providing a potential therapeutic strategy for treating hair loss. However, current methods for isolating DP cells are either inefficient (physical microdissection) or only applied to genetically labeled mice. We systematically screened for the surface proteins specifically expressed in skin DP using mRNA expression databases. We identified two antibodies against receptors LEPTIN Receptor (LEPR ) and Scavenger Receptor Class A Member 5 (SCARA5) which could specifically label and isolate DP cells by flow cytometry from mice back skin at the growth phase. The sorted LEPR+ cells maintained the DP characteristics after culturing in vitro, expressing DP marker alkaline phosphatase and functional factors including RSPO1/2 and EDN3, the three major DP secretory factors that regulate hair follicle epithelial cells and melanocytes. Furthermore, the low-passage LEPR+ DP cells could reconstitute hair follicles on nude mice using chamber graft assay when combined with epithelial stem cells. The method of isolating functional DP cells we established here lays a solid foundation for developing DP cell-based therapy.


Assuntos
Derme , Receptores para Leptina , Animais , Células Cultivadas , Derme/metabolismo , Cabelo/metabolismo , Folículo Piloso , Camundongos , Camundongos Nus , Receptores para Leptina/genética , Receptores para Leptina/metabolismo , Receptores Depuradores Classe A/metabolismo
8.
J Colloid Interface Sci ; 606(Pt 2): 1586-1596, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34500160

RESUMO

Hyaluronic acid (HA), a natural polymer, has gained much attention recently because of its good biocompatibility and extensive availability. Herein, a novel drug delivery system based on hyaluronic acid-tetraphenyl ethylene conjugate (HA-SS-TPE) with glutathione (GSH)-responsiveness for targeted drug delivery is designed. During the self-assembly of HA-SS-TPE, doxorubicin (DOX) is loaded to form DOX-loaded polymeric micelles. These as-prepared DOX-loaded polymeric micelles not only exhibit fluorescent emission, but also fast glutathione-triggered dissociation to unload DOX by responding to tumor microenvironments. In-vitro investigations showed that the DOX-loaded polymeric micelles presented a higher intracellular release ratio in CD44-positive cells (ES2 and Hela) than in CD44-negative cells (MCF-7 and L929). Notably, in vivo investigations showed that DOX@HA-SS-TPE significantly suppressed tumor growth. As a result, such a GSH-responsive drug delivery system with fluorescent feature provides a potential treatment for CD44-overexpressing cancers.


Assuntos
Antineoplásicos , Sistemas de Liberação de Medicamentos , Ácido Hialurônico , Micelas , Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Glutationa/metabolismo , Células HeLa , Humanos , Concentração de Íons de Hidrogênio
9.
Foods ; 10(11)2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34829017

RESUMO

Spices are susceptible to contamination by aflatoxin B1 (AFB1) and ochratoxin A (OTA), which are both mycotoxins with high toxicity and carcinogenicity. In this study, we aimed to develop an immuno-chromatographic strip test for the simultaneous quantification of AFB1 and OTA in spices by spraying the coupled antigens AFB1-ovalbumin (AFB1-OVA) and OTA-ovalbumin (OTA-OVA) on a nitrocellulose membrane. The test strip had high sensitivity, good specificity, and strong stability. The detection limits of these two mycotoxins in Chinese prickly ash, pepper, chili, cinnamon, and aniseed were 5 µg/kg. The false positivity rate was 2%, and the false negativity rate was 0%. The maximum coefficient of variation was 4.28% between batches and 5.72% within batches. The average recovery rates of AFB1 and OTA in spices were 81.2-113.7% and 82.2-118.6%, respectively, and the relative standard deviation (RSD) was <10%. The actual sample detection was consistent with high performance liquid chromatography analysis results. Therefore, the immuno-chromatographic test strips developed in this study can be used for the on-site simultaneous detection of AFB1 and OTA in spices. This method would allow the relevant regulatory agencies to strengthen supervision in an effort to reduce the possible human health hazards of such contaminated spices.

10.
J Agric Food Chem ; 69(33): 9529-9535, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34382788

RESUMO

Forchlorfenuron (CPPU) is a plant growth regulator widely used in kiwifruit production. Although research on the toxicological and environmental effects of CPPU is well-established, the nature and toxicological properties of its metabolites are much less well-known. Using high resolution mass spectrometry and nuclear magnetic resonance, the CPPU previously unidentified metabolites in Xuxiang and Jinyan kiwifruit were identified as N-(2-chloro-4-pyridinyl)-N'-(2-hydroxy-4-methoxyphenyl)-urea (metabolite 1) and N-phenyl-N'-4-pyridinylurea (metabolite 2, CAS: 1932-35-0). Their structures were confirmed by synthesis (metabolite 1) and by comparison with a commercial standard (metabolite 2). Quantitative studies demonstrate that CPPU and its metabolites are mainly retained in the kiwifruit peel, while the content is dependent on the nature of the peel surface, with the smoother peel of Jinyan kiwifruit retaining smaller amounts of the compound. Cell viability experiments in Caco2 and Lo2 cells show that the metabolites may have a lower cytotoxicity compared to the parent compound CPPU.


Assuntos
Actinidia , Células CACO-2 , Frutas , Humanos , Compostos de Fenilureia/toxicidade , Piridinas/toxicidade
11.
ACS Appl Mater Interfaces ; 13(28): 32753-32762, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34236174

RESUMO

Since block copolymers are able to self-assemble into various polymeric architectures, it is intriguing to explore a unique self-assembly strategy for polymers. Two different metallic oxides [manganese dioxide (MnO2) and zinc oxide (ZnO)] are displayed herein to demonstrate this self-assembly mechanism of polymers. In situ generation of metallic oxides induces self-assembly of block copolymers to form polymeric hybrid micelles with tunable stability in aqueous solutions. These final ZnO-cross-linked polymeric micelles exhibited a high drug loading capacity of 0.41 mg mg-1 toward doxorubicin (DOX), whereas DOX-loaded ZnO-cross-linked polymeric micelles could be broken down into Zn2+ and polymer scraps, which facilitated drug release in tumor microenvironments. Both in vitro and in vivo investigations showed that the drug-loaded ZnO-cross-linked polymeric micelles effectively suppressed tumor growth. Accordingly, the present study demonstrates a novel strategy of polymer self-assembly for fabricating polymeric architectures that can potentially provide insight for developing other polymeric architectures.


Assuntos
Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Micelas , Neoplasias/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacos , Resinas Acrílicas/química , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Compostos de Manganês/química , Nanopartículas Metálicas/química , Camundongos Endogâmicos BALB C , Neoplasias/patologia , Óxidos/química , Polietilenoglicóis/química , Óxido de Zinco/química
12.
ACS Appl Mater Interfaces ; 13(31): 36926-36937, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34319074

RESUMO

Synergistic therapy holds promising potential in cancer treatment. Here, the inclusion of catechol moieties, a disulfide cross-linked structure, and pendent carboxyl into the network of polymeric nanogels with glutathione (GSH)-responsive dissociation and pH-sensitive release is first disclosed for the codelivery of doxorubicin (DOX) and bortezomib (BTZ) in synergistic cancer therapy. The pendent carboxyl groups and catechol moieties are exploited to absorb DOX through electrostatic interaction and conjugate BTZ through boronate ester, respectively. Both electrostatic interactions and boronate ester are stable at neutral or alkaline pH, while they are instable in an acidic environment to further recover the activities of BTZ and DOX. The polymeric nanogels possess a superior stability to prevent the premature leakage of drugs in a physiological environment, while their structure is destroyed in response to a typical endogenous stimulus (GSH) to unload drugs. The dissociation of the drug-loaded nanogels accelerates the intracellular release of DOX and BTZ and further enhances the therapeutic efficacy. In vitro and in vivo investigations revealed that the dual-drug loaded polymeric nanogels exhibited a strong ability to suppress tumor growth. This study thus proposes a new perspective on the production of multifunctional polymeric nanogels through the introduction of different functional monomers.


Assuntos
Antineoplásicos/uso terapêutico , Bortezomib/uso terapêutico , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Nanogéis/química , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Bortezomib/química , Catecóis/química , Cistamina/análogos & derivados , Cistamina/metabolismo , Doxorrubicina/química , Combinação de Medicamentos , Sinergismo Farmacológico , Feminino , Glutationa/metabolismo , Humanos , Células MCF-7 , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias/metabolismo , Neoplasias/patologia , Polímeros/química , Ensaios Antitumorais Modelo de Xenoenxerto
13.
J Food Sci ; 86(6): 2346-2357, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34028014

RESUMO

Pesticides are widely used in the process of kiwifruit growth to promote fruit expansion. This study was aimed to assess the effects of pesticides on the quality of kiwifruit by applying high and normal concentrations of forchlorfenuron (CPPU) and thidiazuron (TDZ) to "Xuxiang" (XX) green kiwifruit and "Jinyan" (JY) gold kiwifruit. Sixty kiwifruit trees were used to comprehensively evaluate the effects on the pulp and whole kiwifruit. In addition to the weight gain effect and basic physical-chemical properties (vitamin C, total protein, glucose and fructose, organic acids), the main nutritional qualities (in vitro and cellular antioxidant activity (CAA), and dietary minerals) were also evaluated. The vitamin C content of XX was not affected by pesticides, but the use of CPPU reduced vitamin C of JY pulp by 23% (p < 0.05). Pesticides did not reduce the antioxidant values of XX pulp in vitro but significantly reduced CAA values (32%-47%). In JY pulp, pesticides treatments had no significant effect on antioxidant values in vitro except that CPPU treatments significantly reduced the ferric reducing antioxidant power (FRAP) value by 21% (p < 0.05). Reasonable use of pesticides can effectively improve taste of kiwifruit, increasing kiwifruit weight and the content of certain nutrients. PRACTICAL APPLICATION: Based on observed changes in nutritional components, CPPU may be more suitable for XX while TDZ may be more suitable for JY. The significance of this study may affect kiwifruit farmers and ultimately help improve the sensory quality of kiwifruit.


Assuntos
Actinidia/efeitos dos fármacos , Actinidia/metabolismo , Antioxidantes/análise , Valor Nutritivo/efeitos dos fármacos , Praguicidas/farmacologia
14.
J Colloid Interface Sci ; 592: 227-236, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33662827

RESUMO

Rapid progress has been made for mesoporous silica nanoparticle (MSN) in recent years; however, efforts to fabricate MSN with adjustable size have been met with limited advancement in drug delivery, especially for the synthesis of MSN with adjustable size in the range of 150-300 nm. Herein we report the construction of a series of MSNs with adjustable specific surface area, size, and pore structure, depending on the different silicon monomers selected. The optimized MSN showed large specific surface area and appropriate size distribution for efficiently anchoring doxorubicin (DOX) through the imine linkage formed. Based on the remarkable features of the unique MSN, a novel MSN-based drug delivery system was prepared through the introduction of polydopamine/manganese oxide (PDA/MnO2) coating, which reduced the premature leakage of drugs in physiological environments, and yet facilitated drug release when destroyed by responding to endogenous glutathione (GSH) at the tumor sites. Notably, the transformation of MnO2 to Mn2+ resulted in the collapse of the PDA/MnO2 coating, which facilitated drug release and therefore indicated the controlled release feature. It was demonstrated that the drug-loaded MSN-based drug delivery system delivered drugs into cancer cells and showed effective inhibition against cancer cell growth. These results suggested that the emergence of MSN with adjustable size can expand the application of MSN in drug delivery.


Assuntos
Nanopartículas , Dióxido de Silício , Doxorrubicina/farmacologia , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Compostos de Manganês , Óxidos , Porosidade
15.
Cancer Biol Med ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33764711

RESUMO

Cancer has become a very serious challenge with aging of the human population. Advances in nanotechnology have provided new perspectives in the treatment of cancer. Through the combination of nanotechnology and therapeutics, nanomedicine has been successfully used to treat cancer in recent years. In terms of nanomedicine, nanocarriers play a key role in delivering therapeutic agents, reducing severe side effects, simplifying the administration scheme, and improving therapeutic efficacies. Modulations of the structure and function of nanocarriers for improved therapeutic efficacy in cancer have attracted increasing attention in recent years. Stimuli-responsive nanocarriers penetrate deeply into tissues and respond to external or internal stimuli by releasing the therapeutic agent for cancer therapy. Notably, stimuli-responsive nanocarriers reduce the severe side effects of therapeutic agents, when compared with systemic chemotherapy, and achieve controlled drug release at tumor sites. Therefore, the development of stimuli-responsive nanocarriers plays a crucial role in drug delivery for cancer therapy. This article focuses on the development of nanomaterials with stimuli-responsive properties for use as nanocarriers, in the last few decades. These nanocarriers are more effective at delivering the therapeutic agent under the control of external or internal stimuli. Furthermore, nanocarriers with theranostic features have been designed and fabricated to confirm their great potential in achieving effective treatment of cancer, which will provide us with better choices for cancer therapy.

16.
Transl Cancer Res ; 10(5): 2219-2228, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-35116540

RESUMO

BACKGROUND: Cyclooxygenase 2 (COX-2) is an inducible enzyme which promotes tumorigenesis in many types of cancers. Genetic knockout of COX-2 significantly suppresses the tumorigenesis of skin squamous cell carcinoma (SCC). However, COX-2 inhibitor treatment only showed mild to moderate inhibition on SCC in previous reports. The aim of this study is to solve this contradiction and to re-evaluate the therapeutic potential of targeting COX-2 in SCC. METHODS: COX-2 was knocked down by shRNA in two different SCC cell lines, A431 and SCC-13. The cells proliferation and migration capacity were evaluated by cell growth curves and monolayer scratch assay, respectively. Cancer cells with COX-2 knockdown were also xenografted into Balb/c nude mice and tumor growth curves were recorded over time. In addition, we changed the drug administration route and intraperitoneally injected COX-2 inhibitor celecoxib into mice to evaluate its anti-cancer activity. RESULTS: Knockdown of COX-2 exhibited mild or even no effect on cell proliferation and migration in two different SCC cell lines in vitro. However, when cancer cells were xenografted into nude mice, knockdown of COX-2 significantly suppressed proliferation of cancer cells in tumors. At last, intraperitoneal injection instead of oral administration of COX-2 inhibitor celecoxib potently suppressed tumor growth. CONCLUSIONS: Our results indicate that COX-2 might impact on the interaction between cancer cells and surrounding microenvironments rather than on cancer cells directly, and demonstrate that targeting COX-2 is a very promising therapeutic approach for SCC treatment.

18.
Mol Pharm ; 16(6): 2826-2837, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31063382

RESUMO

A glutathione-sensitive poly[methacrylic acid- co-poly(ethylene glycol) methyl ether methacrylate] (PMAABACy- co-PEGMA) nanogel with tunable stability has been fabricated through covalent and metal double-cross-linking strategies in response to the differential change of GSH concentration between the inside and outside of tumor cells. Herein, the size-controlled PMAA- co-PEGMA that possessed unique core-shell structure was first obtained via adjusting the length of PEGMA. Furthermore, N, N-bis(acryloyl)cystamine was introduced to endow PMAA- co-PEGMA with glutathione-sensitive property. The PMAABACy- co-PEGMA950 nanogel exhibited reasonable particle size and desired hydrodynamic diameter that was further cross-linked by Fe(III) ions to obtain a double-cross-linked PMAABACy/Fe(III)- co-PEGMA950 vehicle. In this double-cross-linked vehicle, the existence of metal cross-linked structure made this vehicle possess favorable structural stability to restrict the premature leakage of therapeutic drug. The introduction of covalent cross-linked structure synchronously imparted the vehicle with glutathione-sensitive property in response to the high intracellular glutathione concentrations in tumor cells to induce its structural transform for realizing the release of drug. Additionally, a series of in vitro evaluations demonstrated that PMAABACy/Fe(III)- co-PEGMA950 displayed remarkable biocompatibility and glutathione-sensitive release toward anticancer drug in the simulated intracellular environment of tumor tissues. Notably, the drug-loaded PMAABACy/Fe(III)- co-PEGMA950 exhibited excellent anticancer activity against tumor cells. The double-cross-linked PMAABACy/Fe(III)- co-PEGMA950 nanogel therefore is expected to be a promising tumor microenvironment-sensitive platform for delivering chemotherapeutic drugs.


Assuntos
Glutationa/química , Nanogéis/química , Nanopartículas/química , Polietilenoimina/química
19.
ACS Appl Bio Mater ; 2(2): 895-905, 2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35016293

RESUMO

A hydrogen peroxide (H2O2)/glutathione (GSH) dual-sensitive nanoplatform holds great promise to alleviate the side effects of chemo drugs and improve their therapeutic efficacy against cancer. The site-specific release of chemo drugs with a low premature release still remains a challenge in the field of chemotherapy. In the present work, a novel and multifunctional drug delivery system (DDS) based on a polymethylacrylic acid core with a cross-linked structure of disulfide bond (PMAABACy), metal-organic framework (MOF) interlayer and biologically inspired polydopamine (PDA) coating was developed, serving as a vehicle for on-demand drug release. The dual-responsive nanoplatform not only prevents the premature leakage of a chemotherapeutic drug but also is sensitive to biologically relevant GSH and H2O2 for the precise delivery of chemotherapeutic drug. Considering the transmission route to DDS at the tumor site, the DDS might first respond to the extracellular H2O2 and then to the intracellular GSH, exhibiting a tunable release of chemotherapeutic drug. Through incubation using tumor cells, the growth of tumor cells could be significantly inhibited. Overall, by integrating these different building modules, this research demonstrates the advantages of the MOF-assisted regulate strategy to DDS for a precise site-specific release against tumor cells with a greatly reduced side effect on normal tissues.

20.
Regul Toxicol Pharmacol ; 97: 152-162, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29909271

RESUMO

The presence of pesticide residues in fruit has been of extensive concern worldwide. In this paper, pesticide residues in peach samples in China and their dietary exposure risks for the Chinese general population and children were evaluated. Thirty-nine different pesticides were detected, and 92.3% of samples contained one or more pesticide residues. The most frequently detected pesticide was carbendazim with a detection rate of 60.6%. Residues for eight pesticides in 3.2% of the samples exceeded their MRLs with the highest exceedance of 345%. The results demonstrated that the chronic dietary risks were extremely low for both the general population and children in China. Acute risks from carbendazim, chlorpyrifos, cyhalothrin, cypermethrin, pyridaben and triazophos exposures for children and triazophos for the general population exceeded the acceptable level in the worst case scenario. Only %ARfD of triazophos exceeded 100 when intakes were calculated at the 97.5th percentile of residue level distribution. The risk scoring scheme showed nine pesticides that were considered to pose a higher risk. Different use suggestions for the 39 detected pesticides were proposed to protect the health of consumers. More strictly controlled management of banned pesticides and those suggested for gradually diminished use until banned is highly recommended.


Assuntos
Dieta , Contaminação de Alimentos/análise , Resíduos de Praguicidas/análise , China , Dieta/efeitos adversos , Frutas/química , Humanos , Resíduos de Praguicidas/efeitos adversos , Medição de Risco , Inquéritos e Questionários
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