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1.
Chem Biol Interact ; 330: 109245, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32866465

RESUMO

The calcineurin inhibitor, cyclosporin A (CsA) is one of the most common immunosuppressive agents used in organ transplantation. However, its clinical use is often limited by several unwanted effects including nephrotoxicity and hepatotoxicity. By using immunohistochemical and ELISA techniques, it was found that CsA administration causes a rapid activation of a disintegrin and metalloproteases-17 (ADAM-17), epidermal growth factor receptor (EGFR) and subsequent ERK1/2 phosphorylation in the liver and kidney of albino mice. Furthermore, this study presents mechanistic relevance of this signaling cascade involving reactive oxygen species (ROS)-mediated ADAM-17/EGFR/ERK1/2 activation as indicated by a clear reduction in ADAM-17 and EGFR activities as well as ERK1/2 phosphorylation when the animals pretreated with Polyethylene glycol-superoxide dismutase (PEG-SOD) before CsA administration. Collectively, our findings demonstrate that CsA has the ability to activate ADAM-17-mediated EGFR/ERK1/2 phosphorylation in the liver and kidney of albino mice in ROS-dependent manner. Finally, these data may support the concept of using antioxidant therapy as a valuable approach for the prevention of CsA-induced nephrotoxicity and hepatotoxicity.


Assuntos
Ciclosporina/toxicidade , Rim/metabolismo , Fígado/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Polietilenoglicóis/farmacologia , Superóxido Dismutase/farmacologia , Proteína ADAM17/metabolismo , Animais , Ciclosporina/farmacologia , Interações Medicamentosas , Receptores ErbB/metabolismo , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Camundongos , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
2.
PLoS One ; 15(7): e0236171, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702047

RESUMO

Cell-substrate adhesion of the social amoeba Dictyostelium discoideum, a model organism often used for the study of chemotaxis, is non-specific and does not involve focal adhesion complexes. Therefore, micropatterned substrates where adherent Dictyostelium cells are constrained to designated microscopic regions are difficult to make. Here we present a micropatterning technique for Dictyostelium cells that relies on coating the substrate with an ∼1µm thick layer of polyethylene glycol (PEG) gel. We show that, when plated on a substrate with narrow parallel stripes of PEG-gel and glass, Dictyostelium cells nearly exclusive adhere to and migrate along the glass stripes, thus providing a model system to study one-dimensional migration of amoeboid cells. Surprisingly, we find substantial differences in the adhesion to PEG-gel and glass stripes between vegetative and developed cells and between two different axenic laboratory strains of Dictyostelium, AX2 and AX4. Even more surprisingly, we find that the distribution of Dictyostelium cells between PEG-gel and glass stripes is significantly affected by the expression of several fluorescent protein markers of the cytoskeleton. We carry out atomic force microscopy based single cell force spectroscopy measurements that confirm that the force of adhesion to PEG-gel substrate can be significantly different between vegetative and developed cells, AX2 and AX4 cells, and cells with and without fluorescent markers. Thus, the choice of parental background, the degree of development, and the expression of fluorescent protein markers can all have a profound effect on cell-substrate adhesion and should be considered when comparing migration of cells and when designing micropatterned substrates.


Assuntos
Movimento Celular , Dictyostelium/citologia , Corantes Fluorescentes/metabolismo , Microtecnologia/métodos , Polietilenoglicóis/farmacologia , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Dictyostelium/efeitos dos fármacos , Géis/farmacologia , Análise Espectral
3.
Anticancer Res ; 40(5): 2497-2507, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366394

RESUMO

BACKGROUND: Spectrin αII contributes to cisplatin and carboplatin resistance in ovarian serous carcinoma cells, and its expression in surgical specimens is a valid predictor of prognosis. We sought to identify effective drugs for spectrin αII-mediated cisplatin-resistant cells. MATERIALS AND METHODS: We employed SKOV3 cells with small interfering RNA-mediated spectrin αII downregulation, serous carcinoma cells (NOS2), cisplatin-resistant cells (NOS2CR2), and oxaliplatin-resistant cells (NOS2OXR). RESULTS: In the drug-sensitivity test, oxaliplatin was not affected by the inhibition of spectrin αII expression and was effective for cisplatin-resistant NOS2CR2 cells. NOS2OXR cells did not express higher levels of spectrin αII compared to NOS2 in western blot analysis. Six non-platinum anticancer drugs were not affected by the inhibition and was effective for resistant NOS2CR2 and NOS2OXR cells. Doxorubicin exhibited potent cytotoxicity at 2 µM against both resistant cell lines. CONCLUSION: Pegylated liposomal doxorubicin/oxaliplatin regimen may be effective for cisplatin-resistant ovarian carcinoma with spectrin αII-overexpression.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Doxorrubicina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Ovarianas/genética , Espectrina/genética , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Doxorrubicina/farmacologia , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Polietilenoglicóis/farmacologia , RNA Interferente Pequeno/genética
4.
AAPS PharmSciTech ; 21(4): 121, 2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32337630

RESUMO

Multidrug resistance is the major problem in cancer treatment nowadays. Compounds from plants are the new targets to solve this problem. Quercetin (QCT), quercetrin (QTR), and rutin (RUT) are potential anticancer flavonoids but their poor water solubility leads to less efficacy. In this study, the polymeric micelles of benzoylated methoxy-poly (ethylene glycol)-b-oligo(ε-caprolactone) or mPEG-b-OCL-Bz loading with the flavonoids were prepared to solve these problems. The flavonoid-loaded micelles showed an average size of 13-20 nm and maximum loading capacity of 35% (w/w). The release of QCT (21%, 3 h) was lower than that of QTR (51%, 3 h) and RUT (58%, 3 h). QCT (free and micelle forms) exhibited significantly higher cytotoxicity against P-glycoprotein-overexpressing leukemia (K562/ADR) cells than QTR and RUT (p < 0.05). The results demonstrated that QCT-loaded micelles effectively reversed cytotoxicity of both doxorubicin (multidrug resistant reversing (δ) values up to 0.71) and daunorubicin (δ values up to 0.74) on K562/ADR cells. It was found that QCT-loaded micelles as well as empty polymeric micelles inhibited P-gp efflux of tetrahydropyranyl Adriamycin. Besides, mitochondrial membrane potential was decreased by QCT (in its free form and micellar formation). Our results suggested that the combination effects of polymeric micelles (inhibiting P-gp efflux) and QCT (interfering mitochondrial membrane potential) might be critical factors contributing to the reversing multidrug resistance of K562/ADR cells by QCT-loaded micelles. We concluded that QCT-loaded mPEG-b-OCL-Bz micelles are the attractive systems for overcoming multidrug-resistant cancer cells.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/síntese química , Antineoplásicos/síntese química , Flavonoides/síntese química , Micelas , Polietilenoglicóis/síntese química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/farmacologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Flavonoides/farmacologia , Humanos , Células K562 , Polietilenoglicóis/farmacologia , Polímeros/síntese química , Polímeros/farmacologia , Solubilidade
5.
Life Sci ; 252: 117646, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32272178

RESUMO

Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cells causing resistance to immunotherapies in cancer tumors. In the current study, various immunogenic and therapeutic features of the combination therapies with non-liposomal Doxorubicin (Dox) and the E75 immunogenic peptide (Pep), derived from the human epidermal receptor-2 (HER-2), are investigated in parallel with their liposomal formulations (Lip-Dox (Doxil®) and Lip-Pep). Therefore, triple injection doses of Lip-Pep were preceded with Dox and Lip-Dox injections in TUBO/breast tumor-bearing BALB/c mice. Chemotherapy with either Dox or Lip-Dox reduced the frequency of MDSCs, the level of reactive oxygen species (ROS), and MDSCs-associated genes of Arg1, iNOS, S100A8, S100A9. Whereas Lip-Pep + Dox and Lip-Pep + Lip-Dox treatments synergistically potentiated the immunized splenocytes to produce INF-γ and enhanced the frequency of the anti-tumor CD8+ and CD4+ T cells as opposed to both chemotherapy and immunotherapy regimens. Chemo-immunotherapy increased the number of tumor-infiltrating lymphocytes (TILs) and reduced the level of CD25+ FoxP3+ T regulatory cells. Taken together, chemo-immunotherapy was the optimum treatment for the limitation of tumor progression as they targeted more cancer-related immune players.


Assuntos
Neoplasias da Mama/terapia , Vacinas Anticâncer/administração & dosagem , Doxorrubicina/análogos & derivados , Receptor ErbB-2/imunologia , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Vacinas Anticâncer/imunologia , Terapia Combinada , Progressão da Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Feminino , Imunoterapia/métodos , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Células Supressoras Mieloides/metabolismo , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/farmacologia
6.
World J Microbiol Biotechnol ; 36(4): 58, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32236741

RESUMO

The commercial production of Morchella mushrooms calls for urgent breeding of excellent varieties or strains with appropriate tools, such as protoplast fusion. However, the protoplast fusion in morels has not been studied. In this paper, interspecific hybridization between cultivated morels of M. importuna and M. sextelata by PEG-induced protoplast fusion was conducted. Apart from functional complementation of double inactivated protoplasts, the fusants were characterized by cultural and cultivated characters and molecular markers of random amplified polymorphic DNA (RAPD). The results suggested that the hybrids and their parents showed significant difference in their inoculum recovery time, mycelial growth rate, yield of cultivation and total amino acid content of ascocarps. Moreover, positive barrage reactions were observed between parental strains as well as between each parent and a hybrid line. A dendrogram created on the basis of RAPD fingerprints exhibited three major clusters, in which morel hybrids showed intra-cluster variations, M. sextelata #6 formed an out group, while M. importuna #4 was phylogenetically closer to morel hybrids. All the results demonstrated that real fusants were obtained in our study. Protoplast fusion may provide an ideal alternative for new strain selection, and thus will promote the healthy development of morel industry.


Assuntos
Agaricales/crescimento & desenvolvimento , Polietilenoglicóis/farmacologia , Protoplastos/fisiologia , Agaricales/classificação , Agaricales/genética , Quimera , DNA Fúngico/genética , Filogenia , Melhoramento Vegetal , Técnica de Amplificação ao Acaso de DNA Polimórfico
7.
Nat Rev Drug Discov ; 19(3): 149-150, 2020 03.
Artigo em Inglês | MEDLINE | ID: covidwho-606
8.
Soft Matter ; 16(11): 2725-2735, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32115597

RESUMO

Transmembrane pH gradient poly(isoprene)-block-poly(ethylene glycol) (PI-b-PEG) polymersomes were investigated for their potential use in the detoxification of ammonia, a metabolite that is excessively present in patients suffering from urea cycle disorders and advanced liver diseases, and which causes neurotoxic effects (e.g., hepatic encephalopathy). Polymers varying in PI and PEG block length were synthesized via nitroxide-mediated polymerization and screened for their ability to self-assemble into polymersomes in aqueous media. Ammonia sequestration by the polymersomes was investigated in vitro. While most vesicular systems were able to capture ammonia in simulated intestinal fluids, uptake was lost in partially dehydrated medium mimicking conditions in the colon. Polymeric crosslinking of residual olefinic bonds in the PI block increased polymersome stability, partially preserving the ammonia capture capacity in the simulated colon environment. These more stable vesicular systems hold promise for the chronic oral treatment of hyperammonemia.


Assuntos
Amônia/química , Portadores de Fármacos/química , Encefalopatia Hepática/tratamento farmacológico , Inativação Metabólica/genética , Amônia/metabolismo , Butadienos/química , Butadienos/farmacologia , Portadores de Fármacos/farmacologia , Fluoresceína-5-Isotiocianato/química , Hemiterpenos/química , Hemiterpenos/farmacologia , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Hepatopatias/complicações , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Metacrilatos/química , Tamanho da Partícula , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Polimerização , Polímeros/química , Polímeros/farmacologia , Força Próton-Motriz/efeitos dos fármacos , Distúrbios Congênitos do Ciclo da Ureia/complicações , Distúrbios Congênitos do Ciclo da Ureia/tratamento farmacológico , Distúrbios Congênitos do Ciclo da Ureia/metabolismo , Água/metabolismo
9.
J Pharmacol Exp Ther ; 373(3): 438-444, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32169839

RESUMO

Opioid-induced constipation (OIC), a typical side effect of opioids, is due to activation of the µ-opioid receptors in the enteric nervous system. Peripherally acting µ-opioid receptor antagonists (PAMORAs) can reverse OIC by inhibiting the peripheral action of opioids without affecting centrally mediated analgesia. Naldemedine is a PAMORA with potent antagonist activity against µ-, δ-, and κ-opioid receptors. In this study, the pharmacological profiles of naldemedine, compared with those of naloxone and naloxegol, were evaluated. In vitro, Schild plot analysis indicated that naldemedine was a noncompetitive antagonist of µ-opioid receptors, whereas other compounds were competitive antagonists. Also, naldemedine showed slower association and dissociation kinetics than the other compounds. In vivo, naldemedine dose-dependently ameliorated morphine-induced inhibition of small intestinal transit (SIT). The dose-response curve was not shifted at 1 and 3 mg/kg morphine. On the contrary, that of naloxegol was significantly shifted to the right from 1 to 3 mg/kg morphine. In morphine-dependent rats, naldemedine caused peripheral withdrawal symptoms (diarrhea) at doses higher than 1 mg/kg, whereas the dose that produced half the maximal preventive effect (ED50) against constipation was 0.03 mg/kg. Naldemedine showed slower onset and a lesser severity of diarrhea than the other compounds at close to the ED50 value in the SIT model. Our results reveal that naldemedine has different pharmacological profiles (type of antagonism and binding kinetics) to the other compounds. This might explain the differential inhibition of morphine-induced SIT and withdrawal symptoms among the three antagonist compounds. SIGNIFICANCE STATEMENT: Naldemedine is a novel peripherally acting µ-opioid receptor antagonist with potent antagonist activity against µ-, δ-, and κ-opioid receptors. Naldemedine showed a noncompetitive antagonism and slower association and dissociation kinetics against µ-opioid receptors than naloxone and naloxegol. Naldemedine showed insurmountable antagonism of morphine-induced inhibition and lower and slower peripheral withdrawal symptoms (diarrhea) than the other compounds. Therefore, naldemedine has a different pharmacological profile (the type of antagonism and binding kinetics) to the other compounds.


Assuntos
Analgésicos Opioides/farmacologia , Morfinanos/farmacologia , Naloxona/farmacologia , Naltrexona/análogos & derivados , Antagonistas de Entorpecentes/farmacologia , Polietilenoglicóis/farmacologia , Receptores Opioides mu/antagonistas & inibidores , Animais , Constipação Intestinal/induzido quimicamente , Masculino , Morfina/farmacologia , Naltrexona/farmacologia , Dor/tratamento farmacológico , Dor/metabolismo , Manejo da Dor/métodos , Ratos , Ratos Wistar , Receptores Opioides kappa/metabolismo
10.
Nat Rev Drug Discov ; 19(3): 149-150, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32127666
11.
Nat Commun ; 11(1): 1435, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188843

RESUMO

Regeneration of corneal stroma has always been a challenge due to its sophisticated structure and keratocyte-fibroblast transformation. In this study, we fabricate grid poly (ε-caprolactone)-poly (ethylene glycol) microfibrous scaffold and infuse the scaffold with gelatin methacrylate (GelMA) hydrogel to obtain a 3 D fiber hydrogel construct; the fiber spacing is adjusted to fabricate optimal construct that simulates the stromal structure with properties most similar to the native cornea. The topological structure (3 D fiber hydrogel, 3 D GelMA hydrogel, and 2 D culture dish) and chemical factors (serum, ascorbic acid, insulin, and ß-FGF) are examined to study their effects on the differentiation of limbal stromal stem cells to keratocytes or fibroblasts and the phenotype maintenance, in vitro and in vivo tissue regeneration. The results demonstrate that fiber hydrogel and serum-free media synergize to provide an optimal environment for the maintenance of keratocyte phenotype and the regeneration of damaged corneal stroma.


Assuntos
Substância Própria/fisiologia , Gelatina/farmacologia , Hidrogéis/farmacologia , Metacrilatos/farmacologia , Poliésteres/farmacologia , Polietilenoglicóis/farmacologia , Regeneração , Animais , Substância Própria/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Limbo da Córnea/citologia , Masculino , Ratos Sprague-Dawley , Regeneração/efeitos dos fármacos , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Estresse Mecânico , Células Estromais/citologia , Células Estromais/efeitos dos fármacos , Suínos , Tecidos Suporte/química , Vimentina/metabolismo
12.
Planta ; 251(3): 65, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060652

RESUMO

MAIN CONCLUSION: Swelling of sweet cherry cell walls is a physical process counterbalanced by turgor. Cell turgor prevents swelling in intact cells, whereas loss of turgor allows cell walls to swell. Swelling of epidermal cell walls precedes skin failure in sweet cherry (Prunus avium) cracking. Swollen cell walls lead to diminished cell:cell adhesions. We identify the mechanism of cell wall swelling. Swelling was quantified microscopically on epidermal sections following freeze/thaw treatment or by determining swelling pressure or swelling capacity of cell wall extracts. Releasing turgor by a freeze/thaw treatment increased cell wall thickness 1.6-fold within 2 h. Pressurizing cell wall extracts at > 12 kPa prevented swelling in water, while releasing the pressure increased swelling. The effect was fully reversible. Across cultivars, cell wall thickness before and after turgor release in two subsequent seasons was significantly correlated (before release of turgor: r = 0.71**, n = 14; after release of turgor: r = 0.73**, n = 14) as was the swelling of cell walls upon turgor release (r = 0.71**, n = 14). Close relationships were also identified for cell wall thickness of fruit of the same cultivars grown in the greenhouse and the field (before release of turgor: r = 0.60, n = 10; after release of turgor: r = 0.78**, n = 10). Release of turgor by heating, plasmolysis, incubation in solvents or surfactants resulted in similar swelling (range 2.0-3.1 µm). Cell wall swelling increased from 1.4 to 3.0 µm as pH increased from pH 2.0 to 5.0 but remained nearly constant between pH 5.0 and 8.0. Increasing ethanol concentration decreased swelling. Swelling of sweet cherry cell walls is a physical process counterbalanced by turgor.


Assuntos
Parede Celular/metabolismo , Frutas/citologia , Prunus avium/citologia , Parede Celular/efeitos dos fármacos , Frutas/efeitos dos fármacos , Sucos de Frutas e Vegetais , Concentração de Íons de Hidrogênio , Osmose , Epiderme Vegetal/citologia , Epiderme Vegetal/efeitos dos fármacos , Polietilenoglicóis/farmacologia , Pressão , Prunus avium/efeitos dos fármacos , Sacarose/farmacologia , Fatores de Tempo
13.
Anticancer Res ; 40(2): 915-921, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014935

RESUMO

BACKGROUND/AIM: This study aimed was to clarify the impact of pegfilgrastim (PEG) 3.6 mg primary prophylaxis of febrile neutropenia (FN) on the average relative dose intensity (ARDI) of neoadjuvant/adjuvant FEC-100 for breast cancer. MATERIALS AND METHODS: This retrospective, single-centre cohort study including 296 patients who received FEC-100 compared PEG and non-PEG groups. The PEG group received PEG 3.6 mg as a single subcutaneous injection in each study cycle. The primary endpoint was the ARDI of FEC-100. The secondary endpoints were patient percentage of ARDI≥85%, factors associated with ARDI≥85%, and reasons for reduced ARDI. RESULTS: The PEG group showed significantly higher mean ARDI (95.6% versus 90.7%, p<0.001) and patient percentage of ARDI≥85% (93.0% versus 79.9%, p=0.001). PEG was significantly associated with ARDI≥85% (p=0.009). Neutropenia and FN, the main reasons for reduced ARDI, were significantly lower in the PEG group (p<0.05). CONCLUSION: Primary PEG 3.6 mg prophylaxis increased the ARDI of FEC-100.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Filgrastim/uso terapêutico , Terapia Neoadjuvante/métodos , Polietilenoglicóis/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Estudos de Coortes , Ciclofosfamida/farmacologia , Ciclofosfamida/uso terapêutico , Epirubicina/farmacologia , Epirubicina/uso terapêutico , Feminino , Filgrastim/farmacologia , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/farmacologia , Estudos Retrospectivos
14.
Dalton Trans ; 49(7): 2209-2217, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32003374

RESUMO

Photothermal therapy (PTT) is a promising treatment for tumors due to its efficiency and non-invasiveness. However, during the PTT treatment, reactive oxygen species (ROS) are produced in response to hyperthermia and thus harm the neighboring normal cells. In this work, a multifunctional theranostic agent (Se@SiO2@Au-PEG/DOX NCs) was exploited to solve this problem by introducing selenium, which can efficiently prevent normal cells from oxidative damage by scavenging reactive oxygen species during photothermal therapy. In addition, the Se@SiO2@Au-PEG/DOX nanocomposites (NCs) not only exhibited excellent properties of combined chemo-thermal synergistic therapy, but also showed no appreciable toxicity towards normal tissues due to the protective effect for continuous release of selenium. Thus, the fabricated Se@SiO2@Au-PEG/DOX NCs provide an integrated solution to overcome the limitations of selenium and PTT, and demonstrate great prospects as a safe and highly reliable theranostic agent.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Fotoquimioterapia , Nanomedicina Teranóstica , Células A549 , Animais , Antibióticos Antineoplásicos/síntese química , Antibióticos Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Doxorrubicina/síntese química , Doxorrubicina/química , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Ouro/química , Ouro/farmacologia , Humanos , Camundongos , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Selênio/química , Selênio/farmacologia , Dióxido de Silício/química , Dióxido de Silício/farmacologia
15.
Sci Adv ; 6(4): eaax8258, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32042897

RESUMO

Patch plays an important role in clinical medicine for its broad applications in tissue repair and regeneration. Here, inspired by the diverse adhesion, anti-adhesion, and responsive structural color phenomena in biological interfaces, we present a hybrid hydrogel film with an adhesive polydopamine (PDA) layer and an anti-adhesive poly(ethylene glycol) diacrylate (PEGDA) layer in an inverse opal scaffold. It was demonstrated that the resultant hydrogel film could serve as a functional tissue patch with an excellent adhesion property on one surface for repairing injured tissues and an anti-adhesion property on the other surface for preventing adverse adhesion. Besides, because of the responsive structural color, the patch was imparted with self-reporting mechanical capability, which could provide a real-time color-sensing feedback to monitor the heartbeat activity. Moreover, the catechol groups on PDA imparted the patch with high tissue adhesiveness and self-healing capability in vivo. These features give the bioinspired patch high potential in biomedical applications.


Assuntos
Hidrogéis , Indóis , Membranas Artificiais , Polietilenoglicóis , Polímeros , Adesivos Teciduais , Animais , Anisotropia , Hidrogéis/química , Hidrogéis/farmacologia , Indóis/química , Indóis/farmacologia , Camundongos , Células NIH 3T3 , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Polímeros/química , Polímeros/farmacologia , Adesivos Teciduais/química , Adesivos Teciduais/farmacologia
16.
Chem Commun (Camb) ; 56(7): 1085-1088, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31894779

RESUMO

We report an elastase-responsive, H2S-releasing hydrogel prepared by covalently crosslinking a mixture of carboxymethylcellulose and poly(ethylene glycol) with an elastase-degradable peptide functionalized with an H2S-releasing S-aroylthiooxime (SATO) unit. Addition of elastase triggered a gel-to-sol transition, which exposed SATOs, leading to more and longer H2S release compared to untriggered gels.


Assuntos
Carboximetilcelulose Sódica/farmacologia , Hidrogéis/farmacologia , Sulfeto de Hidrogênio/metabolismo , Elastase de Leucócito/metabolismo , Polietilenoglicóis/farmacologia , Animais , Carboximetilcelulose Sódica/síntese química , Carboximetilcelulose Sódica/metabolismo , Linhagem Celular , Doxorrubicina/toxicidade , Humanos , Hidrogéis/síntese química , Hidrogéis/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oximas/síntese química , Oximas/metabolismo , Oximas/farmacologia , Polietilenoglicóis/síntese química , Polietilenoglicóis/metabolismo , Substâncias Protetoras/síntese química , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia , Ratos
17.
Expert Opin Investig Drugs ; 29(2): 125-133, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31899984

RESUMO

Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and is strongly associated with obesity and insulin resistance. NAFLD refers to a spectrum of disorders ranging from asymptomatic hepatic steatosis (nonalcoholic fatty liver, NAFL) to nonalcoholic steatohepatitis (NASH), which increases the risk of developing more severe forms of liver disease such as progressive fibrosis, cirrhosis, and liver cancer. Currently, there are no food and drug administration (FDA) approved drugs to treat NASH. Pegbelfermin (BMS-986036) is a PEGylated fibroblast growth factor 21 (FGF21) analogue that is under investigation for the treatment of NASH.Areas covered: We reviewed the (pre)clinical pegbelfermin studies and compared these with other studies that assessed FGF21 and FGF21 analogues in the treatment of NASH.Expert opinion: With no FDA approved treatments available for NASH, there is an urgent need for novel therapies. Pegbelfermin is a systemic treatment with pleiotropic effects on various tissues. Short-term adverse effects are limited, but more research is required to study potential long-term safety issues. In a phase 2a trial, pegbelfermin has shown promising improvements in several NASH related outcomes. However, clinical trials demonstrating long-term benefits on hard outcomes such as liver histology, cirrhosis development, or survival are required for further validation.


Assuntos
Fatores de Crescimento de Fibroblastos/análogos & derivados , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Animais , Progressão da Doença , Drogas em Investigação/efeitos adversos , Drogas em Investigação/farmacologia , Drogas em Investigação/uso terapêutico , Fatores de Crescimento de Fibroblastos/efeitos adversos , Fatores de Crescimento de Fibroblastos/farmacologia , Fatores de Crescimento de Fibroblastos/uso terapêutico , Humanos , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/complicações , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/farmacologia
19.
Mater Sci Eng C Mater Biol Appl ; 108: 110455, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31924042

RESUMO

An amphiphilic biodegradable branched copolymer, mPEG-b-PLGA-g-OCol, was synthesized by grafting copolymer (methoxy polyethylene glycol)-b-Poly (l,d-lactic-co-glycolic acid) (mPEG-b-PLGA) on oligomeric collagen (OCol), to form a branched structure with mPEG-b-PLGA as side chain and OCol as backbone. mPEG-b-PLGA and mPEG-b-PLGA-g-OCol were both amphipathic and can self-assemble into micelles in aqueous solution. The mPEG-b-PLGA-g-OCol micelles showed pH-sensitive behaviors and the particle size below 100 nm in slightly acidic environment such as tumor tissue milieu interieur to perform passive targeting. Observed by SEM, when the solution pH increased from 5 to 9, the morphology of mPEG-b-PLGA-g-OCol micelles changed from small spheres to larger ones to rings. For biodegradable mPEG-b-PLGA-g-OCol, the micelles will gradually degrade in body. Further, doxorubicin (DOX) was effectively loaded in the micelles with drug loading and encapsulation efficiency of 3.48% and 25.8%, respectively. To evaluate antineoplastic effect of DOX-laden micelles in vitro, MTT test, flow cytometry and CLSM were performed and found that DOX-laden micelles exhibited higher cellular proliferation inhibition against HeLa cells. These features indicated that the mPEG-b-PLGA-g-OCol micelles were potential drug carrier for cancer therapy.


Assuntos
Plásticos Biodegradáveis , Portadores de Fármacos , Micelas , Plásticos Biodegradáveis/síntese química , Plásticos Biodegradáveis/química , Plásticos Biodegradáveis/farmacocinética , Plásticos Biodegradáveis/farmacologia , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Poliésteres/síntese química , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/farmacologia , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/farmacologia
20.
Biomater Sci ; 8(3): 997-1006, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31895368

RESUMO

Catheter-induced infection is a severe problem in clinical practice, which induces significant morbidity, mortality and treatment costs. Therefore, there is a great requirement for developing antibacterial surfaces of catheter materials. In the present study, we develop a strategy for constructing self-adaptive antibacterial surfaces with bacterium-triggered antifouling-bactericidal switching properties on polyurethane (PU) via surface-initiated atom-transfer radical polymerization (SI-ATRP). Polymer coating with one hierarchical structure was readily constructed on the PU surface (PU-PQ-PEG), which was composed of poly[2-(dimethyl decyl ammonium)ethyl methacrylate] (PQDMAEMA) brushes as the bactericidal lower layer and polyethylene glycol (PEG) as the antifouling upper layer. The two layers were incorporated with Schiff base structures, which could be broken by the metabolism of bacteria. Under normal and mild infection conditions, PU-PQ-PEG showed excellent antifouling and biocompatible properties against proteins and bacteria. When serious infection occurred and bacteria colonized on the PU-PQ-PEG surface, the bacteria could trigger the self-adaptive antifouling-bactericidal switching of the surface. Furthermore, the self-adaptive antibacterial properties of PU-PQ-PEG were also confirmed by an in vitro circulating model to simulate hydrodynamic conditions. PU-PQ-PEG showed self-adaptive antibacterial performances both under static and hydrodynamic conditions. The results of animal experiments also demonstrated the in vivo anti-infection performance. The present work will provide a promising strategy for developing antibacterial surfaces of catheter materials with hemocompatibility.


Assuntos
Antibacterianos/química , Aderência Bacteriana/efeitos dos fármacos , Cateteres/microbiologia , Polietilenoglicóis/química , Poliuretanos/química , Antibacterianos/farmacologia , Hidrodinâmica , Polietilenoglicóis/farmacologia , Polimerização , Poliuretanos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/fisiologia , Propriedades de Superfície
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