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1.
PLoS One ; 15(4): e0231276, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32275737

RESUMO

OBJECTIVES: Alloyed metallic nanoparticles of silver and copper are effective against intracellular infection. However, systemic toxicity may arise due to the non-specific delivery of the nanoparticles. In addressing the issue, this study deals with the targeting of silver-copper-boron (ACB) nanoparticles to infected osteoblasts, which could decrease systemic toxicity and form the basis of targeting specific markers expressed in bone infections. METHODS: ACB nanoparticles were synthesized and conjugated to the Cadherin-11 antibody (OBAb). The effect of targeting nanoparticles against extracellular and intracellular S. aureus was determined by enumeration of bacterial growth. The binding of the targeting nanoparticles to infected osteoblasts as well as the visualization of live/dead bacteria due to treatment was carried out using fluorescence microscopy. MTT assay was used to determine the viability of osteoblasts with different concentrations of the nanoparticles. RESULTS: The ACB nanoparticles conjugated to OBAb (ACB-OBAb) were effective against extracellular S. aureus. The ACB-OBAb nanoparticles showed a 1.32 log reduction of intracellular S. aureus at a concentration of 1mg/L. The ACB-OBAb nanoparticles were able to bind to the infected osteoblast and showed toxicity to osteoblasts at levels ≥20mg/L. Also, the percentage of silver, copper, and boron in the nanoparticles determined the effectiveness of their antibacterial activity. CONCLUSION: The ACB-OBAb nanoparticles were able to target the osteoblasts and demonstrated significant antibacterial activity against intracellular S. aureus. Targeting shows promise as a strategy to target specific markers expressed on infected osteoblasts for efficient nanoparticle delivery, and further animal studies are recommended to test its efficacy in vivo.


Assuntos
Ligas/farmacologia , Osso e Ossos/citologia , Boro/farmacologia , Cobre/farmacologia , Espaço Intracelular/microbiologia , Nanopartículas Metálicas/química , Prata/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Caderinas/imunologia , Linhagem Celular , Endocitose/efeitos dos fármacos , Humanos , Espaço Intracelular/efeitos dos fármacos , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Osteoblastos/efeitos dos fármacos , Osteoblastos/microbiologia
2.
Inorg Chem ; 59(1): 913-924, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31825210

RESUMO

The ruthenium(II) complexes [RuCl(L1)(L3)]Cl (1), [RuCl(L1)(L4)]Cl (2), [RuCl(L2)(L4)]Cl (3), [RuCl(L1)(L5)]Cl (4), and [RuCl(L2)(L5)]Cl (5) of NNN-donor dipicolylamine (dpa) bases (L4, L5) having BODIPY (boron-dipyrromethene) moieties, NN-donor phenanthroline derivatives (L1, L2), and benzyldipicolylamine (bzdpa, L3) were prepared and characterized by spectroscopic techniques and their cellular localization/uptake and photocytotoxicity studied. Complex 1, as its PF6 salt (1a), has been structurally characterized with help of a single-crystal X-ray diffraction technique. It has a RuN5Cl core with the Cl bonded trans to the amine nitrogen atom of bzdpa. The complexes showed intense absorption spectral bands near 500 nm (ε ≈ 58000 M-1 cm-1) in 2 and 3 and 654 nm (ε ≈ 80000 M-1 cm-1) in 4 and 5 in 1/1 DMSO/DPBS (v/v). Complex 5 having biotin and PEGylated-disteryl BODIPY gave a singlet oxygen quantum yield (ΦΔ) of ∼0.65 in DMSO. Complex 5 exhibited remarkable PDT (photodynamic therapy) activity (IC50 ≈ 0.02 µM) with a photocytotoxicity index (PI) value of >5000 in red light of 600-720 nm in A549 cancer cells. The biotin-conjugated complexes showed better photocytotoxicity in comparison to nonbiotinylated analogues in A549 cells. The complexes displayed less toxicity in HPL1D normal cells in comparison to A549 cancer cells. The emissive BODIPY complexes 3 and 5 (ΦF ≈ 0.07 in DMSO) showed significant mitochondrial localization.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Luz , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Células A549 , Antineoplásicos/síntese química , Antineoplásicos/química , Biotina/química , Biotina/farmacologia , Boro/química , Boro/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Clivagem do DNA/efeitos dos fármacos , Teoria da Densidade Funcional , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Imagem Óptica , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Porfobilinogênio/análogos & derivados , Porfobilinogênio/química , Porfobilinogênio/farmacologia , Rutênio/química , Rutênio/farmacologia
3.
Chem Pharm Bull (Tokyo) ; 67(12): 1278-1283, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31787654

RESUMO

The progesterone receptor (PR) plays an important role in various physiological processes, especially in the female reproductive system, and abnormalities of PR function are associated with several diseases, including some types of cancer. Non-steroidal PR ligands are of interest as candidate drugs for treatment of PR-related diseases without the serious adverse effects that may be caused by steroidal ligands. For the development of non-steroidal PR ligands, both a hydrophobic backbone and a polar functional group corresponding to the 3-carbonyl group of progesterone, which interacts with Gln725 and Arg766 of the PR-ligand binding domain, are critically important. We previously showed that carborane is a useful hydrophobic pharmacophore for PR antagonists, and in this work, we introduced the pentafluorosulfanyl (SF5) group as a novel polar functional group of carborane-based non-steroidal PR antagonists. All the synthesized SF5-containing carborane derivatives exhibited PR-antagonistic activity at micromolar or submicromolar concentration. Among them, compounds 11 are potent progesterone antagonists with submicromolar IC50 values.


Assuntos
Boro/farmacologia , Fluoretos/farmacologia , Receptores de Progesterona/antagonistas & inibidores , Compostos de Enxofre/farmacologia , Boro/química , Fluoretos/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Relação Estrutura-Atividade , Compostos de Enxofre/química
4.
Mater Sci Eng C Mater Biol Appl ; 105: 110099, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546395

RESUMO

Multi-modality strategies of albumin-mediated drug accumulation in tumor, boronate-based active tumor targeting and synergistic cancer therapy were combined together for effective treatment of breast cancer. Herein we report the development of albumin-shell oily-core nanocapsules (NCs), loaded with novel combination of hydrophobic drugs, exemestane (EXE) and hesperetin (HES), for targeted breast cancer therapy. This protein-lipid nanohybrid carrier was successfully fabricated using a simple protein-coating method based on the electrostatic adsorption of negatively charged albumin shell onto the oily core containing cationic surfactant. While EXE was directly encapsulated into the oily core, HES was pre-formulated in the form of phospholipid complex before solubilization in oily phase. In addition to albumin-mediated binding to albondin and SPARC, phenylboronic acid was chemically coupled to the albumin shell to confer additional tumor targeting. The targeted nanocarrier (TNC) demonstrated enhanced internalization into MCF-7 breast cancer cells resulting in synergistic cytotoxic activity with a combination index (CI) of 0.662 and dose reduction index (DRI) of 8.22 and 1.84 for EXE and HES, respectively. In vivo, TNC displayed superior anti-cancer activity in tumor-bearing mice compared to their non-targeted counterparts and the free drug combination. A significant reduction of both tumor volume (7-folds) and Ki67 expression (3-folds) was obtained by the targeted nanocarriers compared to positive control. Overall, the boronic-targeted albumin NCs offer a promising platform for hydrophobic drug combination against cancer therapy.


Assuntos
Androstadienos , Antineoplásicos Fitogênicos , Inibidores da Aromatase , Neoplasias da Mama , Hesperidina , Nanocápsulas , Albuminas/química , Albuminas/farmacocinética , Albuminas/farmacologia , Androstadienos/química , Androstadienos/farmacocinética , Androstadienos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Inibidores da Aromatase/química , Inibidores da Aromatase/farmacocinética , Inibidores da Aromatase/farmacologia , Boro/química , Boro/farmacocinética , Boro/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Hesperidina/química , Hesperidina/farmacocinética , Hesperidina/farmacologia , Humanos , Células MCF-7 , Nanocápsulas/química , Nanocápsulas/uso terapêutico , Fosfolipídeos/química , Fosfolipídeos/farmacocinética , Fosfolipídeos/farmacologia
5.
Molecules ; 24(18)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31509949

RESUMO

The amount of boron accumulated in tumor tissue plays an important role regarding the success of the boron neutron capture therapy (BNCT). In this article, we report a modular system, combining readily available starting materials, like glycine, 1,3,5-triazine and the well-known 9-mercapto-1,7-dicarba-closo-dodecaborane(12), as well as α-d-galactopyranose for increased hydrophilicity, with a novel boron-rich tris-meta-carboranyl thiol.


Assuntos
Terapia por Captura de Nêutron de Boro , Boro/farmacologia , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Boro/química , Compostos de Boro/síntese química , Compostos de Boro/química , Compostos de Boro/farmacologia , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Ésteres/química , Glicina/química , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Estrutura Molecular , Neoplasias/patologia , Compostos de Sulfidrila/química , Compostos de Sulfidrila/farmacologia , Triazinas/química , Triazinas/farmacologia
6.
Mol Biol Rep ; 46(5): 5465-5478, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31368021

RESUMO

Diabetes mellitus is worldwide disease. The life of diabetic patients are dependent on exogenous insulin. Pancreas or particularly islet transplantations are performed for reducing external insulin dependency. External substances are also used to protect the ß-cells from the death or increase insulin secretion. In the current study, two different boron containing compounds (sodium pentaborate pentahydrate-NaB and boric acid-BA) were investigated for their effect on pancreatic cells in terms of pro-apoptotic and anti-apoptotic markers, genes related to insulin production mechanism, pancreatic development and glucose metabolism, some antioxidant enzymes, and genes for the initiation of diabetes, insulin secretion and antioxidant enzyme activities in vitro. The results revealed that boron containing compounds did not lead to apoptosis. On the contrary, they increased cell viability, antioxidant enzyme activities and the level of genes related to insulin production. Overall evaluation, data in the current study showed that boron containing compounds might be promising therapeutic agents for type 1 diabetes. However, additional investigations are strictly needed to elucidate molecular mechanisms of boron containing compounds.


Assuntos
Boratos/farmacologia , Ácidos Bóricos/farmacocinética , Células Secretoras de Insulina/efeitos dos fármacos , Anexina A5 , Apoptose/efeitos dos fármacos , Boratos/metabolismo , Ácidos Bóricos/metabolismo , Boro/metabolismo , Boro/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus/metabolismo , Glutationa Peroxidase , Humanos , Insulina/genética , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Superóxido Dismutase
7.
Colloids Surf B Biointerfaces ; 183: 110387, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31394419

RESUMO

Successful boron neutron capture therapy (BNCT) requires sufficient and specific delivery of boron atoms to malignant cells. Gold nanoparticles (AuNPs) have been used as a useful delivery system for selectively releasing cytotoxic payloads in the tumor. However, studies demonstrating the in vivo distribution or pharmacokinetics of boron-containing AuNPs via noninvasive imaging are lacking. This study aims to develop theranostic AuNP-boron cage assemblies (B-AuNPs) and evaluate its feasibility for BNCT. The commercial citrate-coated AuNPs were subjected to PEGylation, azide addition, and carborane modification on the surface. To further arm the AuNPs, we conjugated anti-HER2 antibody (61 IgG) with boron-containing PEGylated AuNPs to form 61-B-AuNPs. The diameter and radiolabeling efficiency of boron-containing AuNPs were determined by dynamic light scattering (DLS) and radio thin-layer chromatography (radio TLC), respectively. Noninvasive single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging was performed to determine the pharmacokinetics of radioiodinated AuNPs in N87 gastric cancer xenografts, and the content of boron in tumor and muscle was assessed by inductively coupled plasma mass spectrometry (ICP-MS). After the 3-step modification, the diameter of B-AuNPs increased by ˜25 nm, and antibody conjugation did not affect the diameter of AuNPs. Radioactive iodine (I-123) was introduced in AuNPs by Click chemistry under copper catalysis. The radiolabeling efficiency of 123I-B-AuNPs and 123I-61-B-AuNPs was approximately 60 ± 5%. After purification, the radiochemical purity (RCP) of these NPs was greater than 90%. MicroSPECT/CT imaging showed that the tumor-to-muscle (T/M) ratio of 123I-B-AuNP-injected mice reached 1.91 ± 0.17 at 12 h post-injection, while that of 123I-61-B-AuNP-injected mice was 12.02 ± 0.94. However, the increased uptake of AuNPs by the thyroid was observed at 36 h after the administration of 123I-61-B-AuNPs, indicating antibody-mediated phagocytosis. The T/M ratio, assessed by ICP-MS, of B-AuNP- and 61-B-AuNP-injected mice was 4.91 ± 2.75 and 41.05 ± 11.15, respectively. We successfully developed detectable HER2-targeting boron-containing AuNPs with high RCP and an acceptable yield. Noninvasive imaging could be a valuable tool for the noninvasive determination of the pharmacokinetics of AuNPs and measurement of boron concentration in the tumor.


Assuntos
Terapia por Captura de Nêutron de Boro/métodos , Boro/farmacologia , Nanopartículas Metálicas/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Nanomedicina Teranóstica/métodos , Animais , Boro/química , Linhagem Celular Tumoral , Ouro/química , Humanos , Radioisótopos do Iodo/química , Radioisótopos do Iodo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Polietilenoglicóis/química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
8.
ACS Appl Mater Interfaces ; 11(28): 25024-25033, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31260250

RESUMO

Boron doped diamond (BDD), given the robustness of the material, is becoming an electrode of choice for applications which require long-term electrochemical monitoring of analytes in aqueous environments. However, despite the extensive work in this area, there are no studies which directly assess the biofilm formation (biofouling) capabilities of the material, which is an essential consideration because biofouling often causes deterioration in the sensor performance. Pseudomonas aeruginosa is one of the most prevalent bacterial pathogens linked to water-related diseases, with a strong capacity for forming biofilms on surfaces that are exposed to aquatic environments. In this study, we comparatively evaluate the biofouling capabilities of oxygen-terminated (O-)BDD against materials commonly employed as either the packaging or sensing element in water quality sensors, with an aim to identify factors which control biofilm formation on BDD. We assess the monospecies biofilm formation of P. aeruginosa in two different growth media, Luria-Bertani, a high nutrient source and drinking water, a low nutrient source, at two different temperatures (20 and 37 °C). Multispecies biofilm formation is also investigated. The performance of O-BDD, when tested against all other materials, promotes the lowest extent of P. aeruginosa monospecies biofilm formation, even with corrections made for total surface area (roughness). Importantly, O-BDD shows the lowest water contact angle of all materials tested, that is, greatest hydrophilicity, strongly suggesting that for these bacterial species, the factors controlling the hydrophilicity of the surface are important in reducing bacterial adhesion. This was further proven by keeping the surface topography fixed and changing surface termination to hydrogen (H-), to produce a strongly hydrophobic surface. A noticeable increase in biofilm formation was found. Doping with boron also results in changes in hydrophobicity/hydrophilicity compared to the undoped counterpart, which in turn affects the bacterial growth. For practical electrochemical sensing applications in aquatic environments, this study highlights the extremely beneficial effects of employing smooth, O-terminated (hydrophilic) BDD electrodes.


Assuntos
Biofilmes , Incrustação Biológica/prevenção & controle , Boro , Diamante , Pseudomonas aeruginosa/fisiologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Boro/química , Boro/farmacologia , Diamante/química , Diamante/farmacologia , Propriedades de Superfície
9.
J Trace Elem Med Biol ; 55: 6-14, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31345367

RESUMO

INTRODUCTION: Dietary boron improves immune and antioxidant status and calcium metabolism in mammals. However, till date the effects of dietary boron supplementation on male reproduction, especially on sperm production and sperm quality in farm animals are not documented. OBJECTIVE: The present study was aimed to investigate the influence of dietary boron on semen production, semen quality, immunity and molecular changes in the testis, blood and seminal plasma and to assess the interrelationship with other minerals in male goats. METHODOLOGY: The study was conducted in 21 adult male goats divided into 3 groups (control, boron and selenium supplemented groups, n = 7 each). In boron group, boron was supplemented at 40 ppm and in selenium group, selenium was supplemented at 1 ppm over and above the basal level. In control group, only the basal diet was fed without supplementary boron or selenium. The feeding trial was carried out for 60 days. Selenium was taken as a positive control for the dietary boron supplementation experiment. Following feeding trials, the sperm concentration, kinematics and functional attributes, immunity and molecular level changes in the testis, biomolecular changes in the blood and seminal plasma and also interrelationship with other minerals were studied. RESULTS: The average sperm concentration (million/ml) and the total sperm production (million/ejaculate) were significantly (p < 0.05) increased in boron supplemented group when compared to selenium and control groups. The boron levels in blood plasma (r = 0.65) and seminal plasma (r = 0.54) showed a positive correlation with sperm progressive motility. Blood and seminal plasma metabolic biomarker namely, aspartate aminotransferase (AST) (p < 0.01) was significantly lower in the boron and selenium supplemented group than control, while alanine aminotransferase (ALT) (p < 0.05) was significantly lower in the boron supplemented group than selenium and control group. There was a significant increase in the mRNA expression of serine proteinase inhibitor (SERPIN) and interferon γ (IFNγ) in the testis of boron supplemented than the control group. Boron supplementation up-regulated the immune-regulatory gene, interleukin 2 (IL2) and antioxidant gene, catalase (CAT) in the peripheral blood mononuclear cells (PBMC). On contrary, toll-like receptor 2 (TLR2) mRNA expression was significantly (p < 0.05) down-regulated in boron and selenium supplemented groups. CONCLUSION: The study revealed that dietary boron supplementation increased the sperm output, sperm motility and enhanced the immune and antioxidant defense capacity in male goats. The improved semen quality can be attributed to enhanced expression of testicular SERPIN, a crucial protein for the regulation of spermatogenesis process.


Assuntos
Boro/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Sêmen/efeitos dos fármacos , Sêmen/imunologia , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Boro/administração & dosagem , Suplementos Nutricionais , Regulação da Expressão Gênica/genética , Cabras , Masculino , Minerais/química , Minerais/isolamento & purificação , RNA Mensageiro/genética , Selênio/administração & dosagem , Selênio/farmacologia , Análise do Sêmen , Inibidores de Serinopeptidase do Tipo Kazal/genética , Motilidade Espermática/imunologia , Espermatozoides/imunologia , Testículo/imunologia
10.
Eur J Med Chem ; 179: 828-836, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31295715

RESUMO

A ferrocenyl boron dipyrromethene (BODIPY) has been developed and utilized as a dark quencher to construct a cathepsin B-responsive fluorescent probe and photosensitizer. The smart fluorescent probe and photosensitizer (Pc-FcQ) contains a zinc(II) phthalocyanine as the fluorescent and photosensitizing unit which is conjugated to the ferrocenyl BODIPY dark quencher via a cathepsin B-cleavable peptide substrate [Gly-Phe-Leu-Gly-Lys]. The photosensitizing properties of Pc-FcQ, including fluorescence and singlet oxygen generation, are significantly quenched through energy transfer to the BODIPY unit and subsequently by the photoinduced electron transfer from the nearby ferrocenyl moiety. Upon exposure of cathepsin B in human hepatocellular carcinoma HepG cells, the fluorescence emission of Pc-FcQ could be restored, indicating the cleavage of the peptide substrate and the separation of the phthalocyanine and ferrocenyl BODIPY unit. However, the intracellular fluorescence intensity of Pc-FcQ was largely diminished after the cells were pre-treated with cathepsin B inhibitor. Its intracellular fluorescence intensity was comparable to that of the control compound in which the peptide substrate was replaced by the non-cleavable one [Gly-Gly-Gly-Gly-Lys]. The singlet oxygen generation of Pc-FcQ was also examined in HepG2 cells as reflected by the cytotoxicity assay. The Pc-FcQ exhibited higher potency when compared with the non-cleavable analogue due to the cleavage of peptide substrate and the detachment of the BODIPY dark quencher from the phthalocyanine. The activation of the Pc-FcQ was also demonstrated in tumor-bearing nude mice. After intratumoral injection of Pc-FcQ, the fluorescence intensity at the tumor region increased gradually over 10 h as a result of the detachment of the dark quencher upon the action of cathepsin B. All the results suggest that this ferrocenyl BODIPY could serve as an efficient dark quencher and the resulting Pc-FcQ could act as the cathepsin B-responsive fluorescent probe and activatable photosensitizer.


Assuntos
Boro/farmacologia , Catepsina B/farmacologia , Compostos Ferrosos/farmacologia , Corantes Fluorescentes/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Porfobilinogênio/análogos & derivados , Animais , Boro/química , Catepsina B/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Compostos Ferrosos/química , Corantes Fluorescentes/química , Células HT29 , Células Hep G2 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Imagem Óptica , Fármacos Fotossensibilizantes/química , Porfobilinogênio/química , Porfobilinogênio/farmacologia , Relação Estrutura-Atividade , Células Tumorais Cultivadas
11.
Plant Physiol Biochem ; 141: 105-113, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31136933

RESUMO

The boron (B) is an essential nutrient and plays an important role in the stability of the primary cell wall (CW). Due to the narrow window between B deficiency and toxicity, mismanagement practices lead to B toxicity that inhibit root growth and overall crop productivity. However, the exact cause of root growth inhibition remains unclear. The present study examined the potential causes and targets of B toxicity by studying intercellular mechanism. The trifoliate seedlings were cultured under excess B conditions. The results indicated that plant growth was inhibited by excess B, nevertheless, the effects were prominent on roots and leaves. B toxicity exacerbated oxidative stress and root cell death. The analysis of CW functional groups, CW microstructure and B forms lead to the conclusion that alterations in CW, and accumulation of free-B and carbohydrates might cause inhibition of growth and visible symptoms of B toxicity.


Assuntos
Boro/farmacologia , Parede Celular/efeitos dos fármacos , Estresse Oxidativo , Poncirus/efeitos dos fármacos , Poncirus/metabolismo , Antioxidantes/química , Sítios de Ligação , Membrana Celular/metabolismo , Folhas de Planta/efeitos dos fármacos , Raízes de Plantas/metabolismo , Análise de Componente Principal , Plântula/metabolismo , Solo/química , Espectroscopia de Infravermelho com Transformada de Fourier , Xantina Oxidase/química
12.
Ecotoxicol Environ Saf ; 179: 212-221, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31048217

RESUMO

Aluminum (Al) toxicity is a major limiting factor for plant productivity. Boron (B) could mitigate Al toxicity in many plant species. However, information about the mechanisms of B alleviating Al toxicity in citrus is lacking. Trifoliate orange rootstock (Poncirus trifoliate L. Raf.) seedlings were irrigated with a nutrient solution containing two B and two Al levels. Results showed that exposure to Al severely impeded plant growth-related parameters. However, B supply improved plant biomass, root activity and relative root elongation under Al stress. Furthermore, B reduced the Al-induced H2O2 accumulation in roots as evidenced by lower fluorescence intensity of H2O2 staining. Boron decreased the Al-stimulated ascorbate (AsA) synthesis by down-regulated AsA synthesis-related metabolites in the L-galactose pathway. Boron alleviated some of the toxic effects of Al by decreasing redox states of AsA and enzyme activities involved in ascorbate-glutathione (AsA-GSH) cycle, ascorbate peroxidase, dehydroascorbate reductase, glutathione reductase and glutathione peroxidase while increased glutathione (GSH) content and γ-glutamylcysteine synthetase (γ-GCS) activity. Overall, our results suggest that B protects roots against Al-induced oxidative stress possibly by reducing metabolites accumulation in the L-galactose pathway of AsA synthesis and regulating AsA-GSH cycle.


Assuntos
Alumínio/toxicidade , Boro/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Poncirus/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Poluentes do Solo/toxicidade , Irrigação Agrícola , Ascorbato Peroxidases/metabolismo , Ácido Ascórbico/metabolismo , China , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Peróxido de Hidrogênio/metabolismo
13.
Int J Mol Sci ; 20(9)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075903

RESUMO

Boron (B) is a micronutrient for plant development, and its deficiency alters many physiological processes. However, the current knowledge on how plants are able to sense the B-starvation signal is still very limited. Recently, it has been reported that B deprivation induces an increase in cytosolic calcium concentration ([Ca2+]cyt) in Arabidopsis thaliana roots. The aim of this work was to research in Arabidopsis whether [Ca2+]cyt is restored to initial levels when B is resupplied and elucidate whether apoplastic Ca2+ is the major source for B-deficiency-induced rise in [Ca2+]cyt. The use of chemical compounds affecting Ca2+ homeostasis showed that the rise in root [Ca2+]cyt induced by B deficiency was predominantly owed to Ca2+ influx from the apoplast through plasma membrane Ca2+ channels in an IP3-independent manner. Furthermore, B resupply restored the root [Ca2+]cyt. Interestingly, expression levels of genes encoding Ca2+ transporters (ACA10, plasma membrane PIIB-type Ca2+-ATPase; and CAX3, vacuolar cation/proton exchanger) were upregulated by ethylene glycol tetraacetic acid (EGTA) and abscisic acid (ABA). The results pointed out that ACA10, and especially CAX3, would play a major role in the restoration of Ca2+ homeostasis after 24 h of B deficiency.


Assuntos
Arabidopsis/metabolismo , Boro/deficiência , Sinalização do Cálcio , Cálcio/metabolismo , Citosol/metabolismo , Arabidopsis/genética , Boro/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Citosol/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Plântula/efeitos dos fármacos , Plântula/metabolismo
14.
Biomed Res Int ; 2019: 8961409, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31011582

RESUMO

Polycaprolactone (PCL) has attracted great attention for bone regeneration attributed to its cost-efficiency, high toughness, and good processability. However, the relatively low elastic modulus, hydrophobic nature, and insufficient bioactivity of pure PCL limited its wider application for bone regeneration. In the present study, the effects of the addition of boron containing bioactive glass (B-BG) materials on the mechanical properties and biological performance of PCL polymer were investigated with different B-BG contents (0, 10, 20, 30, and 40 wt.%), in order to evaluate the potential applications of B-BG/PCL composites for bone regeneration. The results showed that the B-BG/PCL composites possess better tensile strength, human neutral pH value, and fast degradation as compared to pure PCL polymers. Moreover, the incorporation of B-BG could enhance proliferation, osteogenic differentiation, and angiogenic factor expression for rat bone marrow stromal cells (rBMSCs) as compared to pure PCL polymers. Importantly, the B-BG also promoted the angiogenic differentiation for human umbilical vein endothelial cells (HUVECs). These enhanced effects had a concentration dependence of B-BG content, while 30 wt.% B-BG/PCL composites achieved the greatest stimulatory effect. Therefore the 30 wt.% B-BG/PCL composites have potential applications in bone reconstruction fields.


Assuntos
Indutores da Angiogênese/farmacologia , Materiais Biocompatíveis/farmacologia , Regeneração Óssea/efeitos dos fármacos , Boro/farmacologia , Vidro/química , Osteogênese/efeitos dos fármacos , Poliésteres/química , Animais , Materiais Biocompatíveis/química , Linhagem Celular , Módulo de Elasticidade/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Teste de Materiais/métodos , Células-Tronco Mesenquimais/efeitos dos fármacos , Polímeros/química , Ratos , Ratos Sprague-Dawley , Resistência à Tração/efeitos dos fármacos
15.
J Trace Elem Med Biol ; 53: 136-143, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30910197

RESUMO

Boron is among the necessary nutrients for plant growth and yield production, and it can improve the nutritional properties of forage crops. However, at higher levels it maybe toxic adversely affecting plant growth and forage quality. Plant boron concentration is affected by different parameters including boron fertilization, soil, climate, plant species, etc. A new era in the field of plant fertilization is the use of nano technology. Accordingly, a factorial field experiment on the basis of a complete block design in six replicates was conducted in a 300-hactare agro-industry area. The objectives were to investigate the effects of different boron treatments on alfalfa (Medicago sativa L.): 1) boron concentration, and 2) pigment contents including chlorophyll a, b, total, and carotenoids. Six regions with different properties were selected for the experiment; the soil samples were collected using GPS. The experimental treatments including: 1) soil type (S1-S6), 2) boron sources including boric acid (B1) and nano boron fertilization (B2), and 3) number of spraying (zero-, one-, two-, and three-time) were tested. The nano structure of boric acid-copper in an aqueous medium was produced using the chemical reduction method. The results indicated that soil type, boron source and number of spraying significantly affected (P ≤ 0.01) alfalfa boron concentration and pigment content. The mean of alfalfa boron concentration by B1 and B2 was 103.52 and 111.52% higher than control. The three-time spraying significantly increased B concentration related to the other spraying treatments (P ≤ 0.05) as it resulted in a 207.81% increase compared with the control treatment. The three-time spraying resulted in the highest increase of pigment contents (P ≤ 0.05) including chlorophyll a, b, total, and carotenoids compared with the other treatments. Although the highest boron and pigment contents were resulted by the three-time spraying, the combined use of B2 and the two-time spraying was the most optimum treatment (non-toxic) significantly increasing alfalfa boron and pigment contents (P ≤ 0.05). It would be possible to produce alfalfa at large amounts and with suitable forage quality using boron nano fertilization (synthesized and tested in this research work) under calcareous conditions.


Assuntos
Boro/farmacologia , Fertilizantes/análise , Medicago sativa/efeitos dos fármacos , Nanopartículas/química , Solo/química , Boro/análise
16.
Int J Neurosci ; 129(10): 963-977, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30885023

RESUMO

Purpose: To define the actions of boron on normal neurophysiology and glioblastoma growth. Materials and Methods: PubMed and other relevant databases were searched. Results: Discovery of novel boron compounds in treatment of glioblastoma is being actively investigated, but the majority of such studies is focused on the synthesis of boron compounds as sensitizers to Boron Neutron Capture Therapy (BNCT). Nonetheless, the translational functionality of boron compounds is not limited to BNCT as many boron compounds possess direct tumoricidal activity and there is substantial evidence that certain boron compounds can cross the blood-brain barrier. Moreover, boron-containing compounds interfere with several tumorigenic pathways including intratumoral IGF-I levels, molybdenum Fe-S containing flavin hydroxylases, glycolysis, Transient Receptor Potential (TRP) and Store Operated Calcium Entry (SOCE) channels. Conclusions: Boron compounds deserve to be studied further in treatment of systemic cancers and glioblastoma due to their versatile antineoplastic functions.


Assuntos
Compostos de Boro/uso terapêutico , Terapia por Captura de Nêutron de Boro/métodos , Neoplasias Encefálicas/radioterapia , Glioblastoma/radioterapia , Animais , Boro/metabolismo , Boro/farmacologia , Boro/uso terapêutico , Compostos de Boro/metabolismo , Compostos de Boro/farmacologia , Terapia por Captura de Nêutron de Boro/tendências , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Humanos , Resultado do Tratamento
17.
Plant Physiol Biochem ; 138: 80-90, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30852240

RESUMO

When boron (B) deficiency and aluminum (Al) toxicity co-exist in acidic soils, crop productivity is limited. In the current study, we found that 3 µM of B pretreatment significantly enhances rice root elongation under Al toxicity conditions. Pretreatment with B significantly decreases the deposition of Al in rice apoplasts, suppresses the synthesis of cell wall pectin, inhibits cell wall pectin methylesterase (PME) activity and its gene expression, and increases the expression of OsSTAR1 and OsSTAR2, which are responsible for reducing the Al content in the cell walls. In addition, B pretreatment significantly increases OsALS1 expression, thereby facilitating the transfer of Al from the cytoplasm to the vacuoles. However, B pretreatment had no effect on Al uptake and citric acid secretion. Pretreatment with B significantly increases the activity of ascorbate peroxidase (APX), peroxidase (POD), and catalase (CAT), thus increasing the elimination rate of H2O2 in rice roots. Co-treatment using B and H2O2 does not increase root growth under Al toxicity conditions; it also improves pectin synthesis, enhances PME activity, and increases Al deposition in root cell walls. However, the co-treatment of B and H2O2 scavenger 4-hydroxy-TEMPO has an opposite effect. The above results indicate that applying B fertilizers in acidic soil can help decrease the side effects of Al toxicity on rice growth.


Assuntos
Alumínio/farmacologia , Boro/farmacologia , Parede Celular/metabolismo , Peróxido de Hidrogênio/metabolismo , Oryza/metabolismo , Raízes de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas de Plantas/biossíntese
18.
J Med Chem ; 62(5): 2521-2540, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30730745

RESUMO

A series of pleuromutilins modified by introduction of a boron-containing heterocycle on C(14) of the polycyclic core are described. These analogs were found to be potent anti- Wolbachia antibiotics and, as such, may be useful in the treatment of filarial infections caused by Onchocerca volvulus, resulting in Onchocerciasis or river blindness, or Wuchereria bancrofti and Brugia malayi and related parasitic nematodes resulting in lymphatic filariasis. These two important neglected tropical diseases disproportionately impact patients in the developing world. The lead preclinical candidate compound containing 7-fluoro-6-oxybenzoxaborole (15, AN11251) was shown to have good in vitro anti- Wolbachia activity and physicochemical and pharmacokinetic properties providing high exposure in plasma. The lead was effective in reducing the Wolbachia load in filarial worms following oral administration to mice.


Assuntos
Boro/farmacologia , Diterpenos/farmacologia , Filariose Linfática/tratamento farmacológico , Filaricidas/uso terapêutico , Oncocercose/tratamento farmacológico , Compostos Policíclicos/farmacologia , Wolbachia/efeitos dos fármacos , Wuchereria bancrofti/efeitos dos fármacos , Animais , Boro/química , Diterpenos/química , Filaricidas/farmacocinética , Filaricidas/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Compostos Policíclicos/química
19.
Plant Physiol Biochem ; 137: 93-101, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30771565

RESUMO

Aluminum (Al) toxicity in the acid soils (pH ≤ 5) is the major limiting abiotic factor affecting the productivity of crops. Boron (B) has been reported to alleviate Al toxicity. In spite of recent advances, it is not clear how B relieves Al toxicity. Results demonstrated that Al toxicity hampered the root elongation. Moreover, lumogallion fluorescent molecular probe unequivocally localized mostly bound Al to the periphery of the cell wall (CW) and to the nuclei. Additionally, Al toxicity induced variations in the CW components through the accumulation of pectin and hemicellulose. Nevertheless, B supply reduced callose deposition, increased root growth and reduced changes in the CW components under Al toxicity. Moreover, B supply reduced the un-methylated pectin while increased the degree of methyl esterification of pectin. These results imply that B due to its role in the CW formation could reduce aluminum-induced negative effects on plant growth by attenuating apoplastic Al3+ and changes in the CW components which ultimately results in the improved root growth.


Assuntos
Alumínio/toxicidade , Antioxidantes/metabolismo , Boro/farmacologia , Parede Celular/efeitos dos fármacos , Citrus/efeitos dos fármacos , Alumínio/análise , Alumínio/farmacocinética , Ácido Ascórbico/metabolismo , Boro/farmacocinética , Parede Celular/química , Citrus/citologia , Citrus/metabolismo , Glucanos/metabolismo , Microscopia Confocal , Monoaminoxidase/metabolismo , Células Vegetais/efeitos dos fármacos , Células Vegetais/metabolismo , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Análise de Componente Principal , Xantina Oxidase/metabolismo
20.
Cell Mol Biol (Noisy-le-grand) ; 65(1): 65-72, 2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-30782297

RESUMO

This study was designed to investigate the effect of dietary boron on spatial learning, anxiety, some vitamins and oxidative parameters in rats. Thirty-two Wistar albino male rats were used in the study. The rats were equally divided into four groups with 8 rats each: I control group: standard pellet diet only, II. group: 250 ppm boric acid, III. group: 500 ppm boric acid and IV. group: 1000 ppm boric acid added into standard pellet diet. Over a five-week period, elevated plus-maze test was used for anxiety assessment and Morris water maze test was used for evaluating spatial learning. Additionally, blood samples were obtained at the end of the experiment and were used to determine the serum levels of some vitamins and oxidative parameters. Dietary boron significantly increased weight gain (p<0.001) and food consumption in the 250 ppm and 500 ppm groups (p<0.05). Although boron supplementation had no significant effect on learning and anxiety-related behavior, it had beneficiary effects on memory retention in the 1000 ppm group (p<0.05). Biochemical analyses showed a significant decrease in the MDA levels (p<0.05) and an increase in vitamin D3 levels (p<0.01) in the 500 ppm group, a significant increase in GSH-Px activity in the 250 ppm and 500 ppm groups (p<0.05), and a decrease in vitamin E levels in all the experimental groups (p<0.05). In conclusion, our study demonstrated that dietary boron can be beneficial for health when administered at appropriate doses.


Assuntos
Comportamento Animal/efeitos dos fármacos , Ácidos Bóricos/farmacologia , Boro/farmacologia , Dieta , Aprendizagem/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Glutationa Peroxidase/sangue , Masculino , Malondialdeído/sangue , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Fatores de Tempo , Vitamina A/sangue , Vitamina D/sangue , Vitamina E/sangue
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