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1.
Pestic Biochem Physiol ; 159: 41-50, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400783

RESUMO

Emerging fungal phytodiseases are a food security threat and novel fungicides are in an urgent need. Herein, a series of isobutyrophenone derivatives were designed and synthesized. The derivatives exhibited excellent fungicidal activities against seven fungi. The structure-activity relationship (SAR) study indicated that the introduction of a bromo group at the position 3 or 5 of the phenyl ring, as well as esterification of the 4-hydroxy with a chloroacetyl group, could substantially increase the antifungal activity and spectrum of the compounds. Among all 23 compounds, 2-bromo-3-hydroxy-4-isobutyryl-6-methylphenyl 2-chloroacetate (12b) showed the highest fungicidal activity against all seven tested fungal pathogens with EC50 values ranging from 1.22 to 39.94 µg/mL and exhibited the most potent inhibition against class II fructose-1,6-bisphosphate aldolase with an IC50 of 3.63 µM. The lead compounds were proven to be safe to NIH3T3/293 T cells and silkworm larvae, and relatively stable under different harsh conditions. Detached fruit tests showed the practical potential of lead compounds for fruit (or plant) protection. Taken together, our results indicated that the isobutyrophenone derivatives could be further optimized and developed as advanced leads for new fungicides.


Assuntos
Antifúngicos/química , Antifúngicos/metabolismo , Frutose-Bifosfato Aldolase/metabolismo , Animais , Bombyx/metabolismo , Linhagem Celular , Frutose-Bifosfato Aldolase/genética , Humanos , Larva/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Células NIH 3T3 , Relação Estrutura-Atividade
2.
Chem Pharm Bull (Tokyo) ; 67(8): 849-854, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366834

RESUMO

Regenerative therapy with keratinocyte growth factor (KGF) is a novel therapeutic approach for treatment of chronic wounds. However, KGF cannot be used directly to the wound site due to its physicochemical instability. In previous study, sacran, a natural megamolecular polysaccharide, showed potential properties as a biomaterial for hydrogel film in wound healing. In this study, we fabricated sacran hydrogel film containing KGF (Sac/KGF-HF) and evaluated the effects of Sac/KGF-HF on fibroblasts migration and re-epithelialization process. We successfully prepared a homogenous and -amorphous Sac/KGF-HF by a casting method. In addition, Sac/KGF-HF had a high swelling ratio and flexibility. Sac/KGF-HF promoted a migration process of NIH3T3 cells and improved wound healing ability in mice with a percentage of wound closure reaching 90.4% at 9 d. Interestingly, the addition of KGF in Sac-HF considerably increased the number of epithelial cells compared to control, which is important in the re-epithelialization process. It could be concluded that KGF in Sac-HF has the potential for promoting Sac-HF abilities in wound healing process.


Assuntos
Fator 7 de Crescimento de Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Metilgalactosídeos/farmacologia , Polissacarídeos/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Fator 7 de Crescimento de Fibroblastos/química , Metilgalactosídeos/química , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Polissacarídeos/química
3.
Arq Gastroenterol ; 56(2): 155-159, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31460579

RESUMO

BACKGROUND: Gastric cancer is known as the fourth most common cancer. Current treatments for cancer have damaged the sensitive tissues of the healthy body, and in many cases, cancer will be recurrent. Therefore, need for treatments that are more effective is well felt. Researchers have recently shifted their attention towards antipsychotic dopamine antagonists to treat cancer. The anticancer activities of aripiprazole remain unknown. OBJECTIVE: This study aimed to evaluate the efficacy and safety of aripiprazole on gastric cancer and normal cell lines. METHODS: In this regard, the cytotoxicity and genotoxicity of aripiprazole were investigated in MKN45 and NIH3T3 cell lines by methyl tetrazolium assay and on peripheral blood lymphocytes by micronucleus assay. For this purpose, cells were cultured in 96 wells plate. Stock solutions of aripiprazole and cisplatin were prepared. After cell incubation with different concentrations of aripiprazole (1, 10, 25, 50, 100 and 200 µL), methyl tetrazolium solution was added. For micronucleus assay fresh blood was added to RPMI culture medium 1640 supplemented, and different concentrations of aripiprazole (50, 100 and 200 µL) were added. RESULTS: The finding of present study showed that the IC50 of aripiprazole in the cancer cell line (21.36 µg/mL) was lower than that in the normal cell line (54.17 µg/mL). Moreover, the micronucleus assay showed that the frequency of micronuclei of aripiprazole at concentrations below 200 µM was much less than cisplatin. CONCLUSION: Aripiprazole can be a good cytotoxic compound and good candidate for further studies of cancer therapy.


Assuntos
Aripiprazol/toxicidade , Linfócitos/efeitos dos fármacos , Animais , Humanos , Camundongos , Testes para Micronúcleos/métodos , Testes de Mutagenicidade , Células NIH 3T3/efeitos dos fármacos
4.
Carbohydr Polym ; 219: 210-218, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31151519

RESUMO

Scaffold plays a critical role in stem cell differentiation and tissue regeneration. Composite scaffolds composed of bacterial cellulose (BC) and collagen (Col) in different ratios (1:1, 3:1, 5:1) were fabricated in this study. The composite scaffolds exhibit a well-organized interconnected porous structure, significantly better physical stability than Col scaffold, and more water uptake up to 400%. They were also favorable with cell attachment and growth. After osteogenic induction of umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) for 3 weeks, we found more up-regulated osteogenic markers (collagen type 1, osteocalcin, bone sialoprotein) and significantly elevated proteins and calcium deposition, particularly with BC/Col (5:1) scaffold. When PKH-26 pre-labelled MSC-loaded scaffolds were subcutaneously transplanted in a mouse model, they showed many PKH-26-labelled cells and positive signals of α-smooth muscle actin, for neovascularization in the BC/Col (5:1). The current work demonstrates that our BC/Col composites may be promising as a bone tissue-engineered scaffold.


Assuntos
Celulose/química , Colágeno/química , Gluconacetobacter xylinus/metabolismo , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Regeneração Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Celulose/uso terapêutico , Colágeno/uso terapêutico , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Células NIH 3T3 , Osteogênese/efeitos dos fármacos
5.
Carbohydr Polym ; 219: 423-430, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31151543

RESUMO

Colloidal polyaniline dispersions stabilized with biocompatible polysaccharides, sodium hyaluronate and chitosan (both with two different molecular weights), were successfully formulated. The colloids were characterized by UV-vis spectra, particle-size distributions and morphology, as well as by their biological properties in terms of cytotoxicity and antibacterial activity. Colloids containing both chitosan and hyaluronate showed only mild cytotoxicities, which were mainly governed by the concentration of conducting polyaniline in the colloid. Antibacterial activity of the samples, however, depended both on the type of polysaccharide and the ratio between the stabilizer and polyaniline mass. The colloid synthetized using 0.2 M aniline hydrochloride, 0.1 M ammonium persulfate, and 1 wt.% sodium hyaluronate of molecular weight of 1.8-2.1 × 106 exhibited the highest antibacterial activity against both gram positive and gram negative bacteria. This formulation, therefore, allowed for the formation of potentially stimuli-responsive antibacterial colloidal particles with low cytotoxicity.


Assuntos
Compostos de Anilina , Antibacterianos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Coloides , Ácido Hialurônico/química , Compostos de Anilina/química , Compostos de Anilina/farmacologia , Animais , Coloides/química , Coloides/farmacologia , Escherichia coli/efeitos dos fármacos , Camundongos , Células NIH 3T3 , Nanocompostos/química , Staphylococcus aureus/efeitos dos fármacos
6.
Int J Nanomedicine ; 14: 3427-3438, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190801

RESUMO

Background: Biogenic silver nanoparticles (AgNPs) have wider range of biomedical applications. The present work synthesized Tp-AgNPs using mycelial extract of endophytic fungus Talaromyces purpureogenus (MEEF), characterized, and analyzed for antibacterial, anti-proliferation and cell wounding healing activities. Methods: The synthesized Tp-AgNPs were characterized by UV-visible spectrophotometer (UV-Vis), field emission transmission electron microscopy (FETEM) with energy-dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), particle size analysis (PSA) and X-ray diffraction (XRD). Further, antibacterial activity was determined by Kirby-Bauer test and anti-proliferation activity was tested in human lung carcinoma A549 by water-soluble tetrazolium and flow cytometer assay. In addition, cell wounding healing activity was determined by scratch assay. Results: UV-Vis results displayed a strong absorption peak from 390 nm to 420 nm, which indicated the successful synthesis of Tp-AgNPs. FETEM-EDS results indicated the round and triangle shaped Tp-AgNPs with the average size of 25 nm in accordance with PSA. FTIR analysis indicated the involvement of various functional molecules from MEEF in the synthesis of Tp-AgNPs. XRD result proved nature of Tp-AgNPs as a high-quality crystal. The Tp-AgNPs significantly inhibited the growth of bacterial pathogens at the minimal inhibitory concentration of 16.12 µg.mL-1 for Gram+, and 13.98 µg.mL-1 for Gram- bacteria. Further, Tp-AgNPs (2 µg.mL-1) showed a strong anti-proliferation effect in A549. Interestingly, Tp-AgNPs was not cytotoxic to normal NIH3T3 cells. In addition, the NPs exhibited a strong cell wounding healing activity. Conclusion: This work biosynthesized AgNPs with strong antibacterial, anticancer and cell wound healing properties using endophytic fungus T. purpureogenus.


Assuntos
Antibacterianos/farmacologia , Nanopartículas Metálicas/química , Prata/farmacologia , Talaromyces/metabolismo , Células A549 , Animais , Bactérias/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Sobrevivência Celular , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Humanos , Nanopartículas Metálicas/ultraestrutura , Camundongos , Testes de Sensibilidade Microbiana , Células NIH 3T3 , Prata/química , Cicatrização/efeitos dos fármacos
7.
Histochem Cell Biol ; 152(2): 133-143, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31154480

RESUMO

Actin fulfills important cytoplasmic but also nuclear functions in eukaryotic cells. In the nucleus, actin modulates gene expression and chromatin remodeling. Monomeric (G-actin) and polymerized actin (F-actin) have been analyzed by fluorescence microscopy in the nucleus; however, the resolution at the ultrastructural level has not been investigated in great detail. We provide a first documentation of nuclear actin in mouse fibroblasts by electron microscopy (EM). For this, we employed correlative light and electron microscopy on the same section using actin-directed nanobodies recognizing endogenous monomeric and polymeric actin proteins (so-called nuclear Actin-chromobody-GFP; nAC-GFP). Indeed, using this strategy, we could identify actin proteins present in the nucleus. Here, immunogold-labeled actin proteins were spread throughout the entire nucleoplasm. Of note, nuclear actin was complementarily localized to DAPI-positive areas, the latter marking preferentially transcriptionally inactive heterochromatin. Since actin aggregates in rod structures upon cell stress including neurodegeneration, we analyzed nuclear actin at the ultrastructural level after DMSO or UV-mediated cell damage. In those cells the ratio between cytoplasmic and nuclear gold-labeled actin proteins was altered compared to untreated control cells. In summary, this EM analysis (i) confirmed the presence of endogenous nuclear actin at ultrastructural resolution, (ii) revealed the actin abundance in less chromatin-dense regions potentially reflecting more transcriptionally active euchromatin rather than transcriptionally inactive heterochromatin and (iii) showed an altered abundance of actin-associated gold particles upon cell stress.


Assuntos
Actinas/análise , Núcleo Celular/química , Microscopia Eletrônica/métodos , Microscopia de Fluorescência/métodos , Actinas/metabolismo , Animais , Núcleo Celular/metabolismo , Células Cultivadas , Fibroblastos/química , Fibroblastos/citologia , Camundongos , Células NIH 3T3 , Tamanho da Partícula , Conformação Proteica
8.
Eur J Med Chem ; 177: 259-268, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158743

RESUMO

Unexpected inhibitory effects against eeAChE could be found for a newly synthesized class of caffeic acid phenethyl ester (CAPE) derivatives. Thus, phenethyl-(E)-3-(3,5-dimethoxy-4-phenethoxyphenyl)-acrylate (Ki = 1.97 ±â€¯0.38 µM, Ki´â€¯= 2.44 ±â€¯0.07 µM) and 4-(2-(((E)-3-(3,4-bis(benzyloxy)phenyl)acryloyl)oxy)ethyl)-1,2-phenylene (2E,2'E)-bis(3-(3,4-bis(benzyloxy)phenyl)acrylate) (Ki = 0.72 ±â€¯0.31 µM, Ki´â€¯= 1.80 ±â€¯0.21 µM) showed very good inhibition of eeAChE, while being non cytotoxic for malignant human cancer cells and non-malignant mouse fibroblasts. Also, they are weak inhibitors for BChE (from equine serum).


Assuntos
Ácidos Cafeicos/farmacologia , Inibidores da Colinesterase/farmacologia , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Animais , Butirilcolinesterase/metabolismo , Ácidos Cafeicos/síntese química , Ácidos Cafeicos/química , Ácidos Cafeicos/toxicidade , Domínio Catalítico , Linhagem Celular Tumoral , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/toxicidade , Electrophorus , Cavalos , Humanos , Camundongos , Simulação de Acoplamento Molecular , Células NIH 3T3 , Álcool Feniletílico/síntese química , Álcool Feniletílico/toxicidade
9.
Acta Virol ; 63(2): 169-185, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31230446

RESUMO

A rodent-transmitted enveloped lymphocytic choriomeningitis virus (LCMV) is an RNA virus causing persistent infection. During persistent infection, a unique strain MX of LCMV does not yield infectious virions, therefore it is not able to use a receptor for its dissemination, and spreads by cell-to-cell contacts. Virus can be transported to the neighboring cell by different cellular structures such as tunneling nanotubes or cytonemes. Using q-PCR, immunofluorescence, siRNA and western blot, we show that keratin 1 (K1) is essential for the persistent infection caused by LCMV strain MX, and its absence very effectively slows down the course of infection. In contrast, other LCMV strains, namely Clone 13 and Armstrong, which produce expression of K1, desmosomes in cells expressing K1 (42-MG-BA) but not in cells without K1 expression (NIH/3T3). We conclude that the presence of the virus enhances the K1 expression, while the presence of K1 protein potentiates the viral spread in persistently infected cells. Keywords: lymphocytic choriomeningitis virus; keratin 1; persistent infection; desmosomes; virus transport.


Assuntos
Queratina-1 , Coriomeningite Linfocítica , Vírus da Coriomeningite Linfocítica , Animais , Linhagem Celular , Regulação da Expressão Gênica , Queratina-1/genética , Coriomeningite Linfocítica/genética , Vírus da Coriomeningite Linfocítica/classificação , Vírus da Coriomeningite Linfocítica/fisiologia , Camundongos , Células NIH 3T3
10.
Adv Mater ; 31(33): e1901965, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31237375

RESUMO

Antibacterial photocatalytic therapy has been reported as a promising alternative water disinfection technology for combating antibiotic-resistant bacteria. Numerous inorganic nanosystems have been developed as antibiotic replacements for bacterial infection treatment, but these are limited due to the toxicity risk of heavy metal species. Organic semiconductor photocatalytic materials have attracted great attention due to their good biocompatibility, chemically tunable electronic structure, diverse structural flexibility, suitable band gap, low cost, and the abundance of the resources they require. An all-organic composite photocatalytic nanomaterial C3 N4 /perylene-3,4,9,10-tetracarboxylic diimide (PDINH) heterostructure is created through recrystallization of PDINH on the surface of C3 N4 in situ, resulting in enhanced photocatalytic efficiency due to the formation of a basal heterostructure. The absorption spectrum of this composite structure can be extended from ultraviolet to near-infrared light (750 nm), enhancing the photocatalytic effect to produce more reactive oxygen species, which have an excellent inactivation effect on both Gram-negative and positive bacteria, while demonstrating negligible toxicity to normal tissue cells. An efficient promotion of infectious wound regeneration in mice with Staphylococcus aureus infected dermal wounds is demonstrated. This all-organic heterostructure shows great promise for use in wound disinfection.


Assuntos
Antibacterianos/química , Imidas/química , Nitrilos/química , Perileno/análogos & derivados , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Semicondutores , Animais , Antibacterianos/uso terapêutico , Antibacterianos/toxicidade , Catálise , Sobrevivência Celular , Escherichia coli/efeitos dos fármacos , Feminino , Luz , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Nanoestruturas/química , Nitrilos/uso terapêutico , Nitrilos/toxicidade , Perileno/química , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/toxicidade , Porfirinas/uso terapêutico , Porfirinas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Cicatrização , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia
11.
Genes Dev ; 33(13-14): 799-813, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31171700

RESUMO

Mammalian development requires effective mechanisms to repress genes whose expression would generate inappropriately specified cells. The Polycomb-repressive complex 1 (PRC1) family complexes are central to maintaining this repression. These include a set of canonical PRC1 complexes, each of which contains four core proteins, including one from the CBX family. These complexes have been shown previously to reside in membraneless organelles called Polycomb bodies, leading to speculation that canonical PRC1 might be found in a separate phase from the rest of the nucleus. We show here that reconstituted PRC1 readily phase-separates into droplets in vitro at low concentrations and physiological salt conditions. This behavior is driven by the CBX2 subunit. Point mutations in an internal domain of Cbx2 eliminate phase separation. These same point mutations eliminate the formation of puncta in cells and have been shown previously to eliminate nucleosome compaction in vitro and generate axial patterning defects in mice. Thus, the domain of CBX2 that is important for phase separation is the same domain shown previously to be important for chromatin compaction and proper development, raising the possibility of a mechanistic or evolutionary link between these activities.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento/genética , Complexo Repressor Polycomb 1/química , Animais , Linhagem Celular , Escherichia coli/genética , Camundongos , Camundongos Endogâmicos C57BL , Células NIH 3T3 , Organelas/metabolismo , Mutação Puntual , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Domínios Proteicos , Células Sf9
12.
Carbohydr Polym ; 219: 113-120, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31151507

RESUMO

Honey is an ancient natural wound-healing agent and has been reintroduced to modern clinical wound care as it has various bioactivities. In this study, honey was incorporated into an alginate/PVA-based electrospun nanofibrous membrane to develop an efficient wound dressing material. The morphology and chemical composition of the nanofibrous membrane were observed by scanning electron microscopy and characterized via Fourier transform infrared spectroscopy, respectively, demonstrating that honey was successfully introduced to the nanofibers. The nanofibrous membranes with increasing honey content showed enhanced antioxidant activity, suggesting the ability to control the overproduction of reactive oxygen species. Disc diffusion assay and dynamic contact assay proved the antibacterial activity of the honey loaded nanofibers towards Gram-positive bacterium (Staphylococcus aureus) and Gram-negative bacterium (Escherichia coli). The cytotoxicity assay illustrated the non-cytotoxicity and biocompatibility of the nanofibrous membranes. Therefore, the developed honey/alginate/PVA nanofibrous membranes are promising for wound dressings.


Assuntos
Alginatos , Antibacterianos , Antioxidantes , Mel , Membranas/química , Nanofibras , Alginatos/química , Alginatos/uso terapêutico , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Apiterapia , Escherichia coli/efeitos dos fármacos , Humanos , Camundongos , Células NIH 3T3 , Nanofibras/química , Nanofibras/uso terapêutico , Nanofibras/toxicidade , Curativos Oclusivos , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Cicatrização
13.
J Photochem Photobiol B ; 195: 27-32, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31051327

RESUMO

Platinum and Curcumin conjugation using green chemistry is an attempt to enhance the curcumin effectiveness as an anti-fibrosis. In this study, Platinum and curcumin were conjugated to direct curcumin into the liver. Curcumin platinum nanoparticles (C-PtNPs) were formed by changing curcumin concentration at pH 10. The successful formation of C-PtNPs was recognized with the help of Fourier transform infrared (FTIR) and UV-visible spectrophotometers. The particle size and morphology were studied with the help of dynamic light scattering (DLS) and High-resolution transmission electron microscopy (HR-TEM) respectively. The antimicrobial activity of C-PtNPs, was examined against gram positive and gram negative bacteria. Moreover, the NIH/3 T3 cells were used to test the C-PtNPs activity of modifying initial fibrosis indication. The favorable condition for the synthesis of CPt-NPs was by using curcumin 1.5 mM at pH 10. When compared with free curcumin, C-Pt-NPs exhibited higher activity for decreased production of collagen by NIH/3 T3 cells. Altogether, the formation of C-PtNPs by conjugation of platinum to curcumin is assuring for the curcumin directing to treat the hepatic fibrosis.


Assuntos
Anti-Infecciosos/síntese química , Curcumina/química , Nanopartículas Metálicas/química , Platina/química , Animais , Anti-Infecciosos/farmacologia , Sobrevivência Celular , Curcumina/farmacologia , Curcumina/uso terapêutico , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Cirrose Hepática/prevenção & controle , Camundongos , Microscopia Eletrônica de Transmissão , Células NIH 3T3 , Espectroscopia de Infravermelho com Transformada de Fourier
14.
Life Sci ; 229: 225-232, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31085244

RESUMO

AIMS: Cellular senescence is a well-known cancer prevention mechanism, inducing cancer cells to senescence can enhance cancer immunotherapy. However, how cellular senescence is regulated is not fully understood. Dynamic chromatin changes have been discovered during cellular senescence, while the causality remains elusive. BAZ1A, a gene coding the accessory subunit of ATP-dependent chromatin remodeling complex, showed decreased expression in multiple cellular senescence models. We aim to investigate the functional role of BAZ1A in regulating senescence in cancer and normal cells. MATERIALS AND METHODS: Knockdown of BAZ1A was performed via lentivirus mediated short hairpin RNA (shRNA) in various cancer cell lines (A549 and U2OS) and normal cells (HUVEC, NIH3T3 and MEF). A series of senescence-associated phenotypes were quantified by CCK-8 assay, SA-ß-Gal staining and EdU incorporation assay, etc. KEY FINDINGS: Knockdown (KD) of BAZ1A induced series of senescence-associated phenotypes in both cancer and normal cells. BAZ1A-KD caused the upregulated expression of SMAD3, which in turn activated the transcription of p21 coding gene CDKN1A and resulted in senescence-associated phenotypes in human cancer cells (A549 and U2OS). SIGNIFICANCE: Our results revealed chromatin remodeling modulator BAZ1A acting as a novel regulator of cellular senescence in both normal and cancer cells, indicating a new target for potential cancer treatment.


Assuntos
Neoplasias Ósseas/patologia , Senescência Celular , Montagem e Desmontagem da Cromatina , Proteínas Cromossômicas não Histona/metabolismo , Osteossarcoma/patologia , Fatores de Transcrição/metabolismo , Células A549 , Animais , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Células Cultivadas , Proteínas Cromossômicas não Histona/genética , Fibroblastos/citologia , Fibroblastos/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Células NIH 3T3 , Osteossarcoma/genética , Osteossarcoma/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética
15.
Int J Nanomedicine ; 14: 2773-2780, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118610

RESUMO

Purpose: An important application of silver nanoparticles (Ag NPs) is their use as an antimicrobial and wound dressing material. The aim of this study is to investigate the morphological dependence on the antimicrobial activity and cellular response of Ag NPs. Materials and methods: Ag NPs of various shapes were synthesized in an aqueous solution using a simple method. The morphology of the synthesized Ag NPs was observed via TEM imaging. The antimicrobial activity of the Ag NPs with different morphologies was evaluated against various microorganisms (Escherichia coli [E. coli], Staphylococcus aureus [S. aureus], Pseudomonas aeruginosa [P. aeruginosa]). The antimicrobial activity of the Ag NPs was also examined according to the concentration in terms of the growth rate of E. coli. Results: The TEM images indicated that the Ag NPs with different morphologies (sphere, disk and triangular plate) had been successfully synthesized. The antimicrobial activity obtained from the inhibition zone was in the order of spherical Ag NPs > disk Ag NPs > triangular plate Ag NPs. In contrast, fibroblast cells grew well in all types of Ag NPs when the cell viability was evaluated via an MTT assay. An inductively coupled plasma mass assay showed that the difference in the antimicrobial activities of the Ag NPs was closely associated with the difference in the release rate of the Ag ions due to the difference in the surface area of the Ag NPs. Conclusion: The morphological dependence of the antimicrobial activity of the Ag NPs can be explained by the difference in the Ag ion release depending on the shape. Therefore, it will be possible to control the antimicrobial activity by controlling the shape and size of the Ag NPs.


Assuntos
Anti-Infecciosos/farmacologia , Nanopartículas Metálicas/química , Prata/química , Prata/farmacologia , Animais , Antibacterianos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Íons , Nanopartículas Metálicas/ultraestrutura , Camundongos , Testes de Sensibilidade Microbiana , Células NIH 3T3 , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento
16.
Nanoscale ; 11(18): 9163-9175, 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31038150

RESUMO

Diabetes is a chronic metabolic disorder disease characterized by high blood glucose levels and has become one of the most serious threats to human health. In recent decades, a number of insulin delivery systems, including bulk gels, nanogels, and polymeric micelles, have been developed for the treatment of diabetes. Herein, a kind of glucose and H2O2 dual-responsive polymeric nanogel was designed for enhanced glucose-responsive insulin delivery. The polymeric nanogels composed of poly(ethylene glycol) and poly(cyclic phenylboronic ester) (glucose and H2O2 dual-sensitive groups) were synthesized by a one-pot thiol-ene click chemistry approach. The nanogels displayed glucose-responsive release of insulin and the release rate could be promoted by the incorporation of glucose oxidase (GOx), which generated H2O2 at high glucose levels and H2O2 further oxidizes and hydrolyzes the phenylboronic ester group. The nanogels have characteristics of long blood circulation time, a fast response to glucose, and excellent biocompatibility. Moreover, subcutaneous delivery of insulin to diabetic mice with the insulin/GOx-loaded nanogels presented an effective hypoglycemic effect compared to that of injection of insulin or insulin-loaded nanogels. This kind of nanogel would be a promising candidate for the delivery of insulin in the future.


Assuntos
Glucose Oxidase/química , Glucose/metabolismo , Peróxido de Hidrogênio/metabolismo , Hipoglicemiantes/metabolismo , Insulina/metabolismo , Polietilenoglicóis/química , Polietilenoimina/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Química Click , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Portadores de Fármacos/química , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Glucose/química , Glucose Oxidase/metabolismo , Teste de Tolerância a Glucose , Peróxido de Hidrogênio/química , Hipoglicemiantes/química , Hipoglicemiantes/uso terapêutico , Insulina/química , Insulina/uso terapêutico , Camundongos , Células NIH 3T3 , Polietilenoglicóis/toxicidade , Polietilenoimina/toxicidade
17.
Photochem Photobiol Sci ; 18(6): 1565-1575, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31037283

RESUMO

In this study, the hepatotoxicity, phototoxicity and photosensitizing potential of free dronedarone (DRO) and its inclusion complexes with ß-cyclodextrin (ß-CD) and 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD), prepared by different methods, were investigated by using in vitro cell-based approaches. The results of the 3T3 NRU phototoxicity assay showed that free DRO and the CD-based inclusion complexes did not present any substantial phototoxic potential. The photosensitizing potential was assessed by using THP-1 cells and IL-8 as a biomarker, and the experimental data confirmed that both the free drug and the inclusion complexes are likely to cause skin photosensitization, as they were able to induce IL-8 release after irradiation. Nevertheless, the inclusion complexes obtained by kneading followed by spray-drying induced a lower IL-8 release and also presented a smaller stimulation index in comparison with free DRO, suggesting a reduction in the photosensitizing potential. Finally, the free drug and inclusion complexes were also tested for hepatotoxicity using HepG2 cells. Even though lower IC50 values were found for the inclusion complexes prepared by kneading followed by spray-drying, there was no significant difference, indicating that the complexation of dronedarone did not induce hepatotoxicity. Overall, the obtained data confirmed that the inclusion complexes prepared by kneading followed by spray-drying, especially those based on HP-ß-CD, appeared to be the most promising formulations and, therefore, could be encouragingly explored in the development of novel pharmaceutical dosage forms containing DRO, presumably with reduced side effects and improved safety profile.


Assuntos
Ciclodextrinas/farmacologia , Ciclodextrinas/toxicidade , Dronedarona/farmacologia , Dronedarona/toxicidade , Hepatócitos/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/toxicidade , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ciclodextrinas/química , Relação Dose-Resposta a Droga , Dronedarona/química , Células Hep G2 , Humanos , Interleucina-8/análise , Interleucina-8/metabolismo , Camundongos , Estrutura Molecular , Células NIH 3T3 , Fármacos Fotossensibilizantes/química , Relação Estrutura-Atividade , Células THP-1
18.
Eur J Med Chem ; 176: 195-207, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31103900

RESUMO

Previously, we focused on a series of 2-aminobenzamide-based histone deacetylase (HDAC) inhibitors, compound 9 of which displayed potent HDAC inhibitory activity against HDAC1 and HDAC2, and moderate anti-proliferative activity against several cancer cell lines. In the current study, we have designed and synthesized a series of novel HDAC inhibitors based on thioether moiety with 9 as a lead compound. Representative compounds12 g and 12 h showed apparently potent anti-proliferative activities against five solid cancer cell lines: A549, HCT116, Hela, A375 and SMMC7721, and low cytotoxicity against NIH 3T3 normal cells. Especially, 12 g and 12 h also revealed potent HDAC inhibitory activity against HDAC1, 2 and 3. In addition, the two compounds could arrest cell cycle in G2/M phase and promote cell apoptosis. Moreover, they showed extended inhibition of colony formation and effectively blocked cell migration towards A549 cancer cells. Furthermore, 12 g and 12 h possessed better pharmacokinetic properties than the lead compound 9. Benefiting from these results, we also explored 12 g and 12 h in the A549 xenografts model for in vivo antitumor activity. The in vivo experiment indicated that 12 g and 12 h could evidently augment antitumor activity (TGI = 56.9% and 62.7% respectively).


Assuntos
Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Inibidores de Histona Desacetilases/uso terapêutico , Sulfetos/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacocinética , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Benzamidas/síntese química , Benzamidas/farmacocinética , Benzamidas/toxicidade , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Desenho de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/farmacocinética , Inibidores de Histona Desacetilases/toxicidade , Humanos , Camundongos , Simulação de Acoplamento Molecular , Células NIH 3T3 , Sulfetos/síntese química , Sulfetos/farmacocinética , Sulfetos/toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Molecules ; 24(9)2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-31060332

RESUMO

Hair-coloring products include permanent, semi-permanent and temporary dyes that vary by chemical formulation and are distinguished mainly by how long they last. Domestic temporary hair dyes, such as fuchsin basic, basic red 2 and Victoria blue B, are especially popular because of their cheapness and facile applications. Despite numerous studies on the relationship between permanent hair dyes and disease, there are few studies addressing whether these domestic temporary hair dyes are associated with an increased cancer risk. Herein, to ascertain the bio-safety of these temporary hair dyes, we comparatively studied their percutaneous absorption, hemolytic effect and cytotoxic effects in this paper. Furthermore, to better understand the risk of these dyes after penetrating the skin, experimental and theoretical studies were carried out examining the interactions between the dyes and serum albumins as well as calf thymus (CT)-DNA. The results showed that these domestic temporary hair dyes are cytotoxic with regard to human red blood cells and NIH/3T3 cell lines, due to intense interactions with bovine serum albumin (BSA)/DNA. We conclude that the temporary hair dyes may have risk to human health, and those who use them should be aware of their potential toxic effects.


Assuntos
Eritrócitos/citologia , Tinturas para Cabelo/efeitos adversos , Células NIH 3T3/citologia , Corantes de Rosanilina/efeitos adversos , Animais , Bovinos , Sobrevivência Celular/efeitos dos fármacos , DNA/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Tinturas para Cabelo/química , Tinturas para Cabelo/farmacocinética , Hemólise , Humanos , Camundongos , Simulação de Acoplamento Molecular , Células NIH 3T3/efeitos dos fármacos , Fenazinas/efeitos adversos , Fenazinas/química , Fenazinas/farmacocinética , Corantes de Rosanilina/química , Corantes de Rosanilina/farmacocinética , Albumina Sérica Humana/efeitos dos fármacos , Suínos
20.
Soft Matter ; 15(20): 4200-4207, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31070656

RESUMO

Herein, we have designed and synthesized a novel forky peptide D3F3 that transforms into a hydrogel through crosslinking induced by ZIs stimuli. We have employed D3F3 as a suitable drug carrier that is conjugated with DOX. Since the concentration of zinc ions necessary for triggering gelation falls into the physiological range present in prostate tissue, while other cationic ions fail to trigger at physiological concentrations, the peptide-based drug delivery system (DDS) is injectable and would achieve prostate tissue-specific self-assembly in situ. The D3F3 hydrogels exhibited an optimal gelation time, satisfactory mechanical strength (can be enhanced after incorporation of DOX) as well as excellent thixotropic properties. The DDS reserved some DOX in the prostate 24 h after the injection, making local sustained release possible. In addition, the peptide materials demonstrated no cytotoxicity against normal fibroblast cells and no damage was observed to the prostate tissue of rats. The drug release followed a non-Fickian diffusion model, with no burst release observed. Importantly, the DOX-hydrogel system exhibited good anti-cancer efficacy when incubated with prostate cancer cells DU-145. Therefore, this study lays the groundwork for the future design of tissue-specific DDSs that are triggered by cationic ions (e.g. zinc ions), and the platform could be further developed to incorporate other potent drugs utilized in the field of prostate cancer therapy, thereby increasing their potency and reducing their side effects.


Assuntos
Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Hidrogéis/química , Oligopeptídeos/síntese química , Neoplasias da Próstata/tratamento farmacológico , Animais , Ácido Aspártico/química , Cátions Bivalentes , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Reagentes para Ligações Cruzadas/química , Humanos , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Células NIH 3T3 , Próstata , Zinco/química
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