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1.
Gene ; 806: 145921, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34454033

RESUMO

Maoto, a traditional Japanese medicine (Kampo), is widely used to treat upper respiratory tract infections, including influenza virus infection. Although maoto is known to inhibit pro-inflammatory responses in a rodent model of acute inflammation, its underlying mechanism remains to be determined. In this study, we investigated the involvement of immune responses and noradrenergic function in the inhibitory action of maoto. In a mouse model of polyI:C-induced acute inflammation, maoto was administered orally in conjunction with intraperitoneal injection of PolyI:C (6 mg/kg), and blood was collected after 2 h for measurement of plasma cytokines by ELISA. Maoto significantly decreased PolyI:C-induced TNF-α levels and increased IL-10 production. Neither pretreatment with IL-10 neutralizing antibodies nor T-cell deficiency using nude mice modified the inhibitory effect of maoto, indicating that the anti-inflammatory effects of maoto are independent of IL-10 and T cells. Furthermore, the inhibitory effects of maoto on PolyI:C-induced TNF-α production were not observed in ex vivo splenocytes, suggesting that maoto does not act directly on inflammatory cells. Lastly, pretreatment with a ß-adrenergic receptor antagonist partially cancelled the anti-inflammatory effects of maoto. Collectively, these results suggest that maoto mediates its anti-inflammatory effects via ß-adrenergic receptors in vivo.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Anti-Inflamatórios/farmacologia , Inflamação/prevenção & controle , Interleucina-10/genética , Extratos Vegetais/farmacologia , Receptores Adrenérgicos beta/genética , Administração Oral , Animais , Modelos Animais de Doenças , Efedrina/farmacologia , Regulação da Expressão Gênica , Injeções Intraperitoneais , Interleucina-10/agonistas , Interleucina-10/imunologia , Japão , Masculino , Medicina Kampo/métodos , Camundongos Endogâmicos BALB C , Camundongos Nus , Poli I-C/administração & dosagem , Poli I-C/antagonistas & inibidores , Receptores Adrenérgicos beta/imunologia , Transdução de Sinais , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
2.
Gene ; 806: 145920, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34455026

RESUMO

Depression is deemed a mood disorder characterized by a high rate of relapse. Therefore, overcoming of the recurrent depression is globally expecting. Kososan, a traditional Japanese herbal medicine, has been clinically used for mild depressive mood, and our previous studies have shown some evidence for its antidepressive-like efficacy in experimental animal models of depression. However, it remains unclear whether kososan has beneficial effects on recurrent depression. Here, we examined its effect using a mouse model of modified repeated social defeat stress (SDS) paradigm. Male BALB/c mice were exposed to a 5-min SDS from unfamiliar aggressive CD-1 mice for 5 days. Kososan extract (1.0 kg/kg/day) or an antidepressant milnacipran (60 mg/kg/day) was administered orally for 26 days (days 7-32) to depression-like mice with social avoidant behaviors on day 6. Single 5 min of SDS was subjected to mice recovered from the social avoidance on day 31, and then the recurrence of depression-like behaviors was evaluated on day 32. Hippocampal gene expression patterns were also assayed by DNA microarray analysis. Water- or milnacipran-administered mice resulted in a recurrence of depression-like behaviors by re-exposure of single SDS, whereas kososan-administered mice did not recur depression-like behaviors. Distinct gene expression patterns were also found for treating kososan and milnacipran. Collectively, this finding suggests that kososan exerts a preventive effect on recurrent depression-like behaviors in mice. Pretreatment of kososan is more useful for recurrent depression than that of milnacipran.


Assuntos
Antidepressivos/farmacologia , Depressão/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Proteínas do Tecido Nervoso/genética , Derrota Social , Estresse Psicológico/tratamento farmacológico , Administração Oral , Animais , Depressão/genética , Depressão/fisiopatologia , Depressão/psicologia , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Japão , Masculino , Medicina Kampo/métodos , Camundongos , Camundongos Endogâmicos BALB C , Milnaciprano/farmacologia , Anotação de Sequência Molecular , Proteínas do Tecido Nervoso/classificação , Proteínas do Tecido Nervoso/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Recidiva , Estresse Psicológico/genética , Estresse Psicológico/fisiopatologia
3.
Food Chem ; 366: 130606, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34311233

RESUMO

A natamycin-based non-migratory antimicrobial packaging for extending shelf-life of yogurt drink (Doogh) was developed. Firstly, the surface of low-density polyethylene film (LDPE) was modified with acrylic acid at different times of UV exposure (0-10 min) to produce carboxylic functional groups. Then, natamycin was applied to the UV-treated films to bind covalently with the pendent functional groups. The maximum grafting efficiency (81.96%) was obtained for the 6 min treated film. Moreover, surface properties of films were evaluated by Attenuated Total Reflectance/Fourier Transfer Infrared Spectroscopy (ATR-FTIR) and scanning electron microscopy (SEM). Antifungal activity of different treatments of natamycin grafted film was evaluated against two common spoilage yeasts of Doogh including Rhodotorula mucilaginosa and Candida parapsilosis. Results showed that 6 min treated film provides maximum anti-yeast activity and can be applied to control fungal growth in Doogh. Natamycin-grafted film postponed the yeast spoilage in Doogh and prolonged its shelf-life to 23 days.


Assuntos
Anti-Infecciosos , Natamicina , Anti-Infecciosos/farmacologia , Embalagem de Alimentos , Rhodotorula , Iogurte
4.
Food Chem ; 366: 130626, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34325244

RESUMO

The protective effects of the peptides Asp-Asp-Asp-Tyr (DDDY) and Asp-Tyr-Asp-Asp (DYDD) against AAPH-induced HepG2 cells are unclear. Our objective was to investigate the active sites of these peptides and their cellular antioxidant mechanism. DDDY and DYDD show a direct free radical scavenging effect in reducing ROS levels and maintained cellular antioxidant enzymes at normal levels. The quantum chemistry analysis of the electronic properties of antioxidant activity showed that DYDD has a greater energy in the highest occupied molecular orbital than DDDY, and O58-H59 and N10-H12 were identified as the active antioxidant sites in DYDD and DDDY, respectively, indicating that the inconsistent arrangement of amino acids affects the distribution of the highest occupied orbital energy as well as the active sites; thus, influences the antioxidant activity of peptides. It provide valuable insights into the antioxidant active sites of peptides.


Assuntos
Estresse Oxidativo , Peptídeos , Antioxidantes/farmacologia , Domínio Catalítico , Dipeptídeos
5.
Ann Lab Med ; 42(1): 36-46, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34374347

RESUMO

Background: The emergence of carbapenemase-producing Enterobacteriaceae (CPE) represents a major clinical problem. Recently, the occurrence of CPE has increased globally, but epidemiological patterns vary across region. We report the trends in the genotypic distribution and antimicrobial susceptibility of CPE isolated from rectal and clinical samples during a four-year period. Methods: Between January 2016 and December 2019, 1,254 nonduplicated CPE isolates were obtained from four university hospitals in Korea. Carbapenemase genotypes were determined by multiplex real-time PCR. Antimicrobial susceptibility was profiled using the Vitek 2 system (bioMérieux, Hazelwood, MO, USA) or MicroScan Walkaway-96 system (Siemens West Sacramento, CA, USA). The proportions of carbapenemase genotypes and nonsusceptibility were analyzed using Pearson's chi-square test. Results: Among the 1,254 CPE isolates, 486 (38.8%), 371 (29.6%), 357 (28.5%), 8 (0.6%), 8 (0.6%), and 24 (1.9%) were Klebsiella pneumoniae carbapenemase (KPC), oxacillinase (OXA)-48-like, New Delhi metallo-ß-lactamase (NDM), imipenemase (IMP), Verona integron-encoded metallo-ß-lactamase (VIM), and multiple producers, respectively. The predominant species was K. pneumoniae (72.6%), followed by Escherichia coli (6.5%). More than 90% of the isolates harboring KPC, NDM, and OXA-48-like were nonsusceptible to cephalosporins, aztreonam, and carbapenems. Conclusions: The impact of CPE is primarily due to KPC-, NDM-, and OXA-48-like-producing K. pneumoniae isolates. Isolates carrying these carbapenemase are mostly multidrug-resistant. Control strategies based on these genotypic distributions and antimicrobial susceptibilities of CPE isolates are required.


Assuntos
Anti-Infecciosos , Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Infecções por Enterobacteriaceae/epidemiologia , Genótipo , Hospitais Universitários , Humanos , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , República da Coreia , beta-Lactamases/genética
6.
Food Chem ; 366: 130650, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34330030

RESUMO

Mixed lauric acid esters (MLE) with antibacterial and antioxidative activities were produced through lipase-catalyzed two-step esterification in solvent-free system without purification. In the first reaction, erythorbyl laurate was synthesized for 72 h. Successive reaction for 6 h at molar ratio of 1.0 (lauric acid to glycerol) produced MLE containing erythorbyl laurate and glyceryl laurate with small amounts of residual substrates, by converting 99.52% of lauric acid. MLE addition (0.5-2.0%, w/w) to Tween 20-stabilized emulsions decreased droplet size, polydispersity index, and zeta-potential, possibly enhancing the emulsion stability. In the emulsions, MLE at 0.5 and 2.0% (w/w) caused 4.4-4.6 and 5.9-6.1 log reductions of Gram-positive (Staphylococcus aureus, Listeria monocytogenes) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), respectively, within 12 h. Lipid hydroperoxide concentrations decreased to 50.8-98.3% in the presence of 0.5-2.0% (w/w) MLE. These findings support a novel approach without needing purification to produce multi-functional food additives for emulsion foods.


Assuntos
Ésteres , Lipase , Antibacterianos/farmacologia , Antioxidantes , Catálise , Esterificação , Ácidos Láuricos , Lipase/metabolismo , Solventes
7.
Food Chem ; 366: 130643, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34330031

RESUMO

To protect walnut peptides from harsh external environments during their storage and digestion, proliposomes loaded with walnut peptides were fabricated using sucrose, trehalose, and mannitol as carriers and lyoprotectants. The physicochemical properties, environmental stability, antioxidant/antibacterial activities, and digestion in vitro of the proliposomes were evaluated. The freshly prepared liposomes were uniform in size, but the hydrated proliposomes showed a more uneven size distribution. The lyoprotectants helped maintain favorable liposome shape during lyophilization. Alongside the lyoprotectants, the walnut peptides further stabilized the lipid bilayer. Proliposomes encapsulation didn't impact the peptides' antioxidant activity. Furthermore, walnut peptides-loaded proliposomes exhibited antibacterial activity against Escherichia coli and Staphylococcus aureus. The proliposomes were stable during gastric-phase digestion. The lyoprotectants changed the free fatty acid release behaviors of the proliposomes. These characteristics suggest potential applications for proliposomes as effective delivery systems for biopeptides in food stuffs, thereby protecting bioactivities during storage and passage through the gastrointestinal tract.


Assuntos
Antioxidantes , Juglans , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Lipossomos , Tamanho da Partícula , Peptídeos
8.
Food Chem ; 366: 130608, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34454799

RESUMO

Hydrochar of waste walnut shells (WSH) was synthesized in the eco-friendly subcritical water medium (SWM) and its potential to fight against Klebsiella pneumoniae (K. pneumoniae), Staphylococcus aureus (S. aureus), Candida albicans (C. albicans) and Candida parapsilosis (C. parapsilosis) was investigated. Minimum Inhibitory Concentration (MIC) values of the WSH were 3.01 g/mL, 2.06 g/mL, 1.95 g/mL, and 3.12 g/mL for K. pneumoniae, S. aureus, C. albicans and C. parapsilosis, respectively. Survival of the pathogens was investigated by 3 min surface disinfection test exposure to WSH. While the highest inhibition was seen for C. parapsilosis (96.67%) on paper surface with 0.3 g/mL of bovine serum albumin (BSA), the lowest inhibition was determined for C. albicans (6.44%) on the plastic glass surface with 3 g/mL of BSA. An increase in protein, DNA, and potassium ion (K+) leakage was observed after microorganisms were incubated with WSH. This study provided an experimental basis for the practical application of WSH as a natural sanitizer agent.


Assuntos
Anti-Infecciosos , Juglans , Anti-Infecciosos/farmacologia , Candida albicans , Testes de Sensibilidade Microbiana , Staphylococcus aureus
9.
J Ethnopharmacol ; 282: 114574, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34461187

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Gekko gecko is used as a traditional medicine for various diseases including respiratory disorders in northeast Asian countries, mainly Korea, Japan, and China. AIM OF THE STUDY: Allergic asthma is a chronic respiratory disease caused by an inappropriate immune response. Due to the recent spread of coronavirus disease 2019, interest in the treatment of pulmonary disorders has rapidly increased. In this study, we investigated the anti-asthmatic effects of G. gecko extract (GGE) using an established mouse model of ovalbumin-induced asthma. MATERIALS AND METHODS: To evaluate the anti-asthmatic effects of GGE, we evaluated histological changes and the responses of inflammatory mediators related to allergic airway inflammation. Furthermore, we investigated the regulatory effects of GGE on type 2 helper T (Th2) cell activation. RESULTS: Administration of GGE attenuated asthmatic phenotypes, including inflammatory cell infiltration, mucus production, and expression of Th2 cytokines. Furthermore, GGE treatment reduced Th2 cell activation and differentiation. CONCLUSIONS: These results indicate that GGE alleviates allergic airway inflammation by regulating Th2 cell activation and differentiation.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Medicina Tradicional do Leste Asiático , Muco/metabolismo , Ovalbumina , Extratos Vegetais/uso terapêutico , Animais , Asma/induzido quimicamente , Asma/patologia , Líquido da Lavagem Broncoalveolar , COVID-19 , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Imunoglobulina E/imunologia , Mediadores da Inflamação/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Pandemias , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Triptaminas/farmacologia
10.
Talanta ; 236: 122899, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635272

RESUMO

A real-time quartz crystal microbalance (QCM) cytosensor was first developed for dynamical and noninvasive monitoring of cell viscoelasticity for evaluation of apoptosis degree. In this work, human breast cancer cells MCF-7 and MDA-MB-231 were employed as cell model and respectively captured on the surface of QCM electrode modified with mercaptosuccinic acid and poly-l-lysine. Cell viscoelasticity was measured dynamically by real-time monitoring energy dissipation with QCM, and the dynamic diagram of the energy dissipation of MDA-MB-231 cells treated with curcumin was first obtained. The results displayed that the changes of energy dissipation in MDA-MB-231 cells and MCF-7 cells were 8.81 × 10-6 and 5.29 × 10-6, particularly due to the difference in cell viscoelasticity. Furthermore, curcumin was used to induce cell apoptosis and suppress energy dissipation of MDA-MB-231 cells. Combining apoptosis assay with QCM measurement, the results revealed good linear relationship between cell viscoelasticity inhibition and apoptosis rate with correlation coefficient R = 0.9908. The QCM cytosensor could rapidly, accurately, dynamically, and noninvasively monitor the changes of cell viscoelasticity for evaluation of apoptosis degree in MDA-MB-231 cells. The study established a new model for cell apoptosis assessment, facilitating understanding of the mechanisms of cell apoptosis on the aspect of mechanical properties.


Assuntos
Técnicas Biossensoriais , Neoplasias da Mama , Curcumina , Apoptose , Neoplasias da Mama/tratamento farmacológico , Curcumina/farmacologia , Feminino , Humanos , Viscosidade
11.
Food Chem ; 369: 130875, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34438342

RESUMO

Cardoon seeds collected in Greece at four different maturity stages (samples S1 to S4) were analysed in terms of chemical composition and in vitro bioactivities. The content of phenolic compounds (six compounds in total) increased with increasing maturity, and 3,5-O-dicaffeyolquinic (14.8-33.8 mg/g extract) acid was the compound detected in higher abundance. Mature seeds (sample S4) also revealed the highest content in lipids (23 g/100 g extract) and tocopherols (29.62 mg/100 g dw) and demonstrated the highest cytotoxic (GI50 of 97-216 µg/mL) and anti-inflammatory (IC50 = 148 µg/mL) activities, and capacity to inhibit the formation of thiobarbituric acid reactive substances (TBARS) (IC50 = 5 µg/mL). Cardoon seed hydroethanolic extracts also revealed high antibacterial and antifungal potential, particularly samples S3 and S1, respectively. This study proved the multifaceted potential associated with valorisation of cardoon seeds, while their biological and chemical composition can be influenced by the maturity stage.


Assuntos
Cynara , Anti-Inflamatórios , Fenóis/análise , Extratos Vegetais/farmacologia , Sementes/química
12.
Food Chem ; 368: 130864, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34438172

RESUMO

Ultra-high pressure (UHP) is a novel non-thermal pretreatment method in food processing for improving the extraction yield of polyphenols and functional properties. The present work investigated the phenolic profiles, antioxidant activities, and cytoprotective effects of the free, esterified, and insoluble-bound phenolic fractions from mango leaves before and after ultra-high pressure (UHP) treatment. UHPLC-Q-Orbitrap-MS/MS analysis resulted in the identification of 42 phenolic compounds in the different phenolic forms. UHP pretreatment could significantly influence the contents of total phenols, total flavonoids and individual compounds in the different phenolic fractions (p < 0.05). After UHP pretreatment, these phenolic fractions exhibited greater antioxidant activity, and inhibited reactive oxygen species production and cell apoptosis (p < 0.05). Meanwhile, IBP were the most potential antioxidative and cytoprotective ingredients. Therefore, UHP pretreated mango leaves with enhanced bioactivity could be used as biological agents in the health food industry to improve its application and economic values.


Assuntos
Antioxidantes , Mangifera , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Fenóis/análise , Extratos Vegetais/farmacologia , Folhas de Planta/química , Espectrometria de Massas em Tandem
13.
Food Chem ; 368: 130871, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34438174

RESUMO

This study is the first dynamic simulation of gastrointestinal digestion of cranberry polyphenols [1 g cranberry extract per day (206.2 mg polyphenols) for 18 days]. Samples from the simulated ascending, transverse, and descending colon of the dynamic gastrointestinal simulator simgi® were analyzed. Results showed that 67% of the total cranberry polyphenols were recovered after simulated gastrointestinal digestion. Specifically, benzoic acids, hydroxycinnamic acids, phenylpropionic acids, phenylacetic acids, and simple phenols were identified. Cranberry feeding modified colonic microbiota composition of Enterococcaceae population significantly. However, increments in microbial-derived short-chain fatty acids, particularly in butyric acid, were observed. Finally, the simgi® effluent during cranberry feeding showed significant antiadhesive activity against uropathogenic Escherichia coli (13.7 ± 1.59 % of inhibition). Understanding the role that gut microbiota plays in cranberry metabolism could help to elucidate its interaction with the human body and explain cranberry protective effects against urinary tract infections.


Assuntos
Vaccinium macrocarpon , Bactérias/genética , Digestão , Humanos , Extratos Vegetais/farmacologia , Polifenóis/farmacologia
14.
Food Chem ; 368: 130832, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34474242

RESUMO

Piper nigrum L. is commonly used worldwide and its pericarp, stalks, leaves will be major wastes materials. 42 amide alkaloids were identified in black, white pepper and pericarp by UHPLC-LTQ-Orbitrap HRMS method, followed by 40 constituents in stalks and 36 constituents in leaves. 8 amide alkaloids were reported for the first time in P. nigrum. An ultra-high-performance supercritical fluid chromatography (UHPSFC)-MS method was firstly applied to simultaneously determine 9 characteristic constituents (piperine, piperlonguminine, piperanine, pipercallosine, dehydropipernonaline, pipernonatine, retrofractamide B, pellitorine and guineensine). The most abundant compound in each extract was piperine with a concentration from 0.10 to 12.37 mg/g of dry weight. The fruits, pericarp and leaves extracts could improve cell viability in 6-OHDA-induced SK-N-SH and SH-SY5Y cells. The results showed the characteristics of amide alkaloids of different parts of P. nigrum and evaluated their neuroprotective activities.


Assuntos
Alcaloides , Piper nigrum , Piper , Alcaloides/farmacologia , Benzodioxóis , Frutas , Extratos Vegetais/farmacologia , Folhas de Planta , Alcamidas Poli-Insaturadas/farmacologia
15.
Food Chem ; 368: 130782, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34392121

RESUMO

In this study, the aerial parts and bulbs of nine Allium species were investigated for their functional phytochemical profile, in vitro antioxidant activities, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-amylase, α-glucosidase, and tyrosinase inhibitory properties. Phenolics, alkaloids, glucosinolates and other sulfur-containing compounds were distinctively profiled in the different species. Maceration in methanol allowed recovering the highest cumulative phenolic content in A. scabrifolium (42.31 mg/g), followed by A. goekyigiti (33.15 mg/g) and A. atroviolaceum (28.35 mg/g). The aerial parts of all Allium species showed high in vitro antioxidant activity whereas methanolic extract of A. cappadocicum bulb showed the highest inhibition against AChE (2.44 mg galantamine equivalent/g) and the water extracts of A. isauricum aerial part were the best BChE inhibitors (4.31 mg galantamine equivalent/g). Bulbs were the richer source of oligosaccharides, and in vitro digestion determined an increase of oligosaccharides bioaccessibility. A promising nutraceutical potential could be highlighted in our understudied Allium species.


Assuntos
Allium , Antioxidantes , Acetilcolinesterase , Antioxidantes/farmacologia , Butirilcolinesterase , Inibidores Enzimáticos , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia
16.
J Colloid Interface Sci ; 605: 296-310, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34329981

RESUMO

This paper presents the design of a new type of intelligent and versatile all-in-one therapeutic nanoplatform for the co-delivery of chemotherapeutic drugs and photosensitizers to facilitate multimodal antitumor treatment; the system is based on hyaluronic acid (HA)-modified manganese dioxide (MnO2)-enveloped hollow porous copper sulfide (CuS) nanoparticles (CuS@MnO2/HA NPs). In this system, a CuS inner shell allows for the co-loading of doxorubicin (DOX) and indocyanine green (ICG) and induces photothermal effects, and a biodegradable MnO2 external shell affords on-demand tumor microenvironment (TME)-triggered release and catalase- andFenton-like activities. Moreover, the HA modification endows the system with a CD44 receptor-mediated tumor-targeting property. The formulated DOX and ICG co-loaded CuS@MnO2/HA (DOX/ICG-CuS@MnO2/HA) NPs were found to exhibit excellent photothermal performance both in vitro and in vivo. In addition, DOX/ICG-CuS@MnO2/HA NPs were found to display both TME and near-infrared (NIR)-responsive controlled release properties. The NPs also have a superior reactive oxygen species (ROS) generation capacity due to the combination of enhanced ICG-induced singlet oxygen and CuS@MnO2-mediated hydroxyl radicals. The cellular uptake, fluorescence imaging property, cytotoxicity, and thermal imaging of these NPs were also evaluated. In tumor-bearing mice, the DOX/ICG-CuS@MnO2/HA NPs displayeda superior antitumor efficacy (2.57-fold) as compared with free DOX. Therefore, the developed DOX/ICG-CuS@MnO2/HA NPs have a great potential for use as an all-in-one nanotherapeutic agent for the efficient and precise induction of chemo/photothermal/photodynamic/chemodynamic therapy with superior antitumor efficacy and fewer side effects.


Assuntos
Nanopartículas , Preparações Farmacêuticas , Animais , Cobre , Doxorrubicina/farmacologia , Ácido Hialurônico , Compostos de Manganês , Camundongos , Óxidos , Fármacos Fotossensibilizantes , Fototerapia , Sulfetos
17.
J Colloid Interface Sci ; 605: 263-273, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34332405

RESUMO

Calcium based biomaterials were widely used for drug delivery application due to their biodegradability, biocompatibility, and high drug loading capacity. Herein, amino-capped polyamidoamine (PAMAM) dendrimer was applied as a macromolecular template to form amino-modified calcium phosphate hollow sphere (CaPO-NH2). After loading with 5-fluorouracil (5Fu), this system performed synergistic cancer chemotherapy. In this study, the 5Fu/CaPO-NH2 particles could be efficiently uptaken by cancer cells, and then decompose into Ca2+ and release 5Fu drug in the cytoplasm; therefore calcium overload and reactive oxygen species (ROS) accumulation were found in PSN1 cells that could induce cell membrane damage and elicit cell apoptosis through a series of biochemical reactions including endoplasmic reticulum stress, lipid peroxidation and mitochondrial apoptosis. In the PSN1 pancreatic cancer xenograft model, the 5Fu/CaPO-NH2 system performed high tumor inhibition via chemotherapy and calcium overload induced apoptosis. Comparingly, the normal cells and organs were insensitive to this synergistic therapy, which indicated the well biocompatibility of delivery system. Thus, this study provided a promising CaPO-NH2 drug delivery platform for enhanced 5Fu chemotherapeutic effect.


Assuntos
Fluoruracila , Neoplasias Pancreáticas , Apoptose , Fosfatos de Cálcio , Linhagem Celular Tumoral , Portadores de Fármacos , Fluoruracila/farmacologia , Humanos , Neoplasias Pancreáticas/tratamento farmacológico
18.
J Colloid Interface Sci ; 605: 727-740, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34365309

RESUMO

Developing durable photocatalysts with highly efficient antibiotics degradation is crucial for environment purification. Herein, tetra (4-carboxyphenyl) porphyrin (TCPP) was loaded onto the surface of Bi2MoO6 microspheres to gain hierarchical organic-inorganic TCPP/Bi2MoO6 (TCPP/BMO) heterojunctions via a facile impregnation strategy. The catalytic properties of these catalysts were comprehensively investigated through the photodegradation of tetracycline hydrochloride (TC) under visible light. Among all the TCPP/BMO heterojunctions, the highest photodegradation rate constant (0.0278 min-1) was achieved with 0.25 wt% TCPP (TCPP/BMO-2), which was approximately 1.15 folds greater than that of pristine Bi2MoO6 and far superior to pure TCPP. The extremely high photocatalytic performance is attributed to the interfacial interaction between TCPP and Bi2MoO6, which favors the efficient separation of charge carriers and the enhancement of visible-light absorbance. TCPP/BMO-2 possesses high mineralization capability and good recycling performance. Photo-induced O2-, h+, and OH were mainly responsible for the degradation of TC. The degradation pathways of TC and toxicity of degradation intermediates were analyzed based on the intermediates detected by the high performance liquid chromatography-mass spectrometer (HPLC-MS) and the toxicity assessment by the quantitative structure-activity relationship (QSAR) prediction. A possible photocatalytic mechanism over TCPP/BMO is proposed. This work offers an insight in developing the porphyrin-based organic-inorganic heterojunctions for effectively remedying pharmaceutical wastewater.


Assuntos
Porfirinas , Tetraciclina , Antibacterianos/farmacologia , Bismuto , Molibdênio
19.
J Colloid Interface Sci ; 605: 851-862, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34371428

RESUMO

Photodynamic therapy (PDT) of tumor has achieved good results, but the treatment efficiency is not high due to the lack of effective photosensitizers and tumor hypoxia. In this study, iridium dioxide nanoparticles (IrO2 NPs) with excellent photothermal/photodynamic effects and catalase like activity were synthesized by a simple method. The combination of glucose oxidase (GOx) and IrO2 NPs is formed by hyaluronic acid (HA), which have the activities of glucose oxidase and catalase, can target tumor sites and form in situ amplifiers in tumor microenvironment (IrO2-GOx@HA NPs). Firstly, GOx convert the high levels of glucose in the tumor to hydrogen peroxide (H2O2), and then IrO2 NPs convert H2O2 to oxygen (O2), which can enhance the type II of PDT. IrO2 NPs also can be used as a thermosensitive agent for photothermal therapy (PTT). In cancer cells, IrO2-GOx@HA NPs-mediated amplifier enhances the effect of type II of PDT, aggravating the apoptosis of breast cancer (4T1) cells and cooperating with its own PTT to further improve the overall treatment effect. Under simulated hypoxic conditions of tumor tissue, it was found that IrO2-GOx@HA NPs treatment can effectively relieve hypoxia inside tumor tissue. In addition, the results in vivo further proved that, IrO2-GOx@HA NPs can enhance the role of II PDT and cooperate with PTT to treat breast cancer effectively. The results highlight the prospect of IrO2-GOx@HA NPs in controlling and regulating tumor hypoxia to overcome the limitations of current cancer therapy.


Assuntos
Neoplasias da Mama , Nanopartículas , Neoplasias , Fotoquimioterapia , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Humanos , Peróxido de Hidrogênio , Irídio , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Terapia Fototérmica , Microambiente Tumoral
20.
Med Gas Res ; 12(1): 18-23, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34472498

RESUMO

Cytoreg is an ionic therapeutic agent comprising a mixture of hydrochloric, sulfuric, phosphoric, hydrofluoric, oxalic, and citric acids. In diluted form, it has demonstrated efficacy against human cancers in vitro and in vivo. Although Cytoreg is well tolerated in mice, rats, rabbits, and dogs by oral and intravenous administration, its mechanism of action is not documented. The acidic nature of Cytoreg could potentially disrupt the pH and levels of ions and dissolved gases in the blood. Here, we report the effects of the intravenous administration of Cytoreg on the arterial pH, oxygen and carbon dioxide pressures, and bicarbonate, sodium, potassium, and chloride concentrations. Our results demonstrate that Cytoreg does not disturb the normal blood pH, ion levels, or carbon dioxide content, but increases oxygen levels in rats. These data are consistent with the excellent tolerability of intravenous Cytoreg observed in rabbits, and dogs. The study was approved by the Bioethics Committee of the University of the Andes, Venezuela (CEBIOULA) (approval No. 125) on November 3, 2019.


Assuntos
Equilíbrio Ácido-Base , Antineoplásicos , Animais , Antineoplásicos/farmacologia , Bicarbonatos/farmacologia , Cães , Concentração de Íons de Hidrogênio , Camundongos , Coelhos , Ratos , Ratos Wistar
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