Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 56
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Adv Colloid Interface Sci ; 275: 102046, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31757388

RESUMO

Fluorescent carbon dots (CDs) are an emerging class of nanomaterials in the carbon family. There are various inexpensive and renewable resources that can be used to synthesize green CDs, which have received immense attention from researchers because of their improved aqueous solubility, high biocompatibility, and eco-friendly nature compared with chemically derived CDs. Additional surface passivation is not required, as heteroatoms are present on the surface of green CDs in the form of amine, hydroxyl, carboxyl, or thiol functional groups, which can improve their physicochemical properties, quantum yield, and the probability of visible light absorption. Green CDs have potential applications in the fields of bioimaging, drug/gene delivery systems, catalysis, and sensing. Since their discovery, there have been several review articles that describe the synthesis of green CDs and some of their applications. However, there are no review articles describing the synthesis and complete applications of green CDs. Here, we provide detailed information regarding their synthesis and applications based on the available literature. In addition, we discuss some of the less explored applications of green CDs and the challenges that remain to be overcome.

2.
Chemosphere ; 238: 124647, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31466007

RESUMO

Ground water arsenic contamination is a global menace. Since arsenic may affect the immune system, leading to immunesuppression, we investigated the effects of acute arsenic exposure on the thymus and spleen using Swiss albino mice, exposed to 5 ppm, 15 ppm and 300 ppm of sodium arsenite for 7 d. Effects on cytokine balance and cell survivability were subsequently analyzed. Our data showed that arsenic treatment induced debilitating alterations in the tissue architecture of thymus and spleen. A dose-dependent decrease in the ratio of CD4+-CD8+ T-cells was observed along with a pro-inflammatory response and redox imbalance. In addition, pioneering evidences established the ability of arsenic to induce an up regulation of Hsp90, eventually resulting in stabilization of its client protein Beclin-1, an important autophagy-initiating factor. This association initiated the autophagic process, confirmed by co-immunoprecipitation assay, acridine orange staining and Western blot, indicating the effort of cells trying to survive at lower doses. However, increased arsenic assault led to apoptotic cell death in the lymphoid organs, possibly by increased ROS generation. There are several instances of autophagy and apoptosis taking place either simultaneously or sequentially due to oxidative stress. Since arsenic is a potent environmental stress factor, exposure to arsenic led to a dose-dependent increase in both autophagy and apoptosis in the thymus and spleen, and cell death could therefore possibly be induced by autophagy. Therefore, exposure to arsenic leads to serious effects on the immune physiology in mice, which may further have dire consequences on the health of exposed animals.


Assuntos
Arsênico/farmacologia , Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Animais , Apoptose/efeitos dos fármacos , Arsenitos/farmacologia , Relação CD4-CD8 , Inflamação/induzido quimicamente , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Compostos de Sódio/farmacologia , Baço/efeitos dos fármacos , Baço/patologia , Timo/efeitos dos fármacos , Timo/patologia
3.
J Nanobiotechnology ; 17(1): 92, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31451110

RESUMO

Carbon dots (CDs) are the new fellow of carbon family having a size less than 10 nm and attracted much attention of researchers since the last decade because of their unique characteristics, such as inexpensive and facile synthesis methods, easy surface modification, excellent photoluminescence, outstanding water solubility, and low toxicity. Due to these unique characteristics, CDs have been extensively applied in different kind of scientific disciplines. For example in the photocatalytic reactions, drug-gene delivery system, in vitro and in vivo bioimaging, chemical and biological sensing as well as photodynamic and photothermal therapies. Mainly two types of methods are available in the literature to synthesize CDs: the top-down approach, which refers to breaking down a more massive carbon structure into nanoscale particles; the bottom-up approach, which refers to the synthesis of CDs from smaller carbon units (small organic molecules). Many review articles are available in the literature regarding the synthesis and applications of CDs. However, there is no such review article describing the synthesis and complete application of CDs derived from small organic molecules together. In this review, we have summarized the progress of research on CDs regarding its synthesis from small organic molecules (bottom-up approach) via hydrothermal/solvothermal treatment, microwave irradiation, ultrasonic treatment, and thermal decomposition techniques as well as applications in the field of bioimaging, drug/gene delivery system, fluorescence-based sensing, photocatalytic reactions, photo-dynamic therapy (PDT) and photo-thermal (PTT) therapy based on the available literature. Finally, the challenges and future direction of CDs are discussed.

4.
BMJ Case Rep ; 12(6)2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31256046

RESUMO

Dorsal dermal sinus (DDS) represents the spectrum of spinal dysraphism. Children may present with features of meningitis. A 13-month male child presented with features of meningitis and quadriparesis. Clinical examination revealed a small pit over the thoracic spine. MRI was suggestive of a DDS. Initially, the patient responded to antibiotics and methylprednisolone, which was given for resolving the mass effect. However, he had a recurrence of symptoms and underwent surgical exploration and resection of DSS with resolution of symptoms. Careful examination of the back is extremely essential in children with meningitis. Radiological investigation helps in visualisation of the DSS. Although rare in children, they may present with recurrent meningitis.


Assuntos
Imagem por Ressonância Magnética/métodos , Quadriplegia , Espinha Bífida Oculta/diagnóstico por imagem , Espinha Bífida Oculta/cirurgia , Diagnóstico Diferencial , Humanos , Lactente , Masculino , Meningite/etiologia , Espinha Bífida Oculta/complicações , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/cirurgia
5.
J Nanobiotechnology ; 17(1): 84, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291944

RESUMO

BACKGROUND: Nanoceria has recently received much attention, because of its widespread biomedical applications, including antibacterial, antioxidant and anticancer activity, drug/gene delivery systems, anti-diabetic property, and tissue engineering. MAIN BODY: Nanoceria exhibits excellent antibacterial activity against both Gram-positive and Gram-negative bacteria via the generation of reactive oxygen species (ROS). In healthy cells, it acts as an antioxidant by scavenging ROS (at physiological pH). Thus, it protects them, while in cancer cells (under low pH environment) it acts as pro-oxidant by generating ROS and kills them. Nanoceria has also been effectively used as a carrier for targeted drug and gene delivery in vitro and in vivo models. Besides, nanoceria can also act as an antidiabetic agent and confer protection towards diabetes-associated organ pathophysiology via decreasing the ROS level in diabetic subjects. Nanoceria also possesses excellent potential in the field of tissue engineering. In this review, firstly, we have discussed the different methods used for the synthesis of nanoceria as these are very important to control the size, shape and Ce3+/Ce4+ ratio of the particles upon which the physical, chemical, and biological properties depend. Secondly, we have extensively reviewed the different biomedical applications of nanoceria with probable mechanisms based on the literature reports. CONCLUSION: The outcome of this review will improve the understanding about the different synthetic procedures and biomedical applications of nanoceria, which should, in turn, lead to the design of novel clinical interventions associated with various health disorders.


Assuntos
Cério/química , Nanopartículas/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Cério/farmacologia , Sistemas de Liberação de Medicamentos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Engenharia Tecidual/métodos
6.
Mater Sci Eng C Mater Biol Appl ; 100: 129-140, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30948047

RESUMO

Naturally occurring bioactive compounds are gaining much importance as anti-tumor agents in recent times due to their high therapeutic potential and less systemic toxicity. However, different preclinical and clinical studies have noted significant shortcomings, such as nonspecific tumor targeting and low bioavailability which limit their usage in therapeutics. Therefore, a safe and compatible nanoparticle mediated controlled drug delivery system is in high demand to enable effective transport of the drug candidates in the tumor tissue. Herein, we have synthesized phenylboronic acid (PBA) conjugated Zinc oxide nanoparticles (PBA-ZnO), loaded with quercetin (a bioflavonoid widely found in plants), with zeta potential around -10.2 mV and diameter below 40 nm. Presence of PBA moieties over the nanoparticle surface facilitates targeted delivery of quercetin to the sialic acid over-expressed cancer cells. Moreover, Quercetin loaded PBA-ZnO nanoparticles (denoted as PBA-ZnO-Q) showed pH responsive drug release behavior. Results suggested that PBA-ZnO-Q induced apoptotic cell death in human breast cancer cells (MCF-7) via enhanced oxidative stress and mitochondrial damage. In line with the in vitro results, PBA-ZnO-Q was found to be effective in reducing tumor growth in EAC tumor bearing mice. Most interestingly, PBA-ZnO-Q is found to reduce tumor associated toxicity in liver, kidney and spleen. The cytotoxic potential of the nanohybrid is attributed to the combinatorial cytotoxic effects of quercetin and ZnO in the cancer cells. Overall, the presented data highlighted the chemotherapeutic potential of the novel nanohybrid, PBA-ZnO-Q which can be considered for clinical cancer treatment.


Assuntos
Portadores de Fármacos/química , Nanopartículas Metálicas/química , Quercetina/química , Óxido de Zinco/química , Animais , Apoptose/efeitos dos fármacos , Ácidos Borônicos/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Quercetina/farmacologia , Quercetina/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Transplante Heterólogo
7.
J Adv Res ; 18: 161-172, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31032117

RESUMO

Nanoparticle-mediated targeted delivery of bioactive natural compounds has recently been gaining much interest for breast cancer therapy. Herein, phenyl boronic acid (PBA)-conjugated and pH-responsive ZnO nanoparticles (diameter ∼40 nm) were synthesized for the tumor tissue-specific delivery of curcumin. PBA conjugation facilitates the targeted delivery of curcumin to the sialic acid overexpressed in breast cancer cell membranes. Curcumin-loaded ZnO nanoparticles (ZnO-PBA-Curcumin) caused apoptotic cell death in MCF-7 human breast cancer cells by inducing oxidative stress and mitochondrial damage. Further, in vivo intravenous (i.v.) administration of ZnO-PBA-Curcumin was found to effectively decrease tumor growth in Ehrlich ascites carcinoma (EAC) tumor-bearing mice via the enhanced accumulation of curcumin. Interestingly, ZnO-PBA-Curcumin did not show any signs of systemic toxicity. The cytotoxic potential of the nanohybrid ZnO-PBA-Curcumin is attributed to the combinatorial cytotoxic effects of curcumin and ZnO in cancer cells. Collectively, ZnO-PBA-Curcumin may represent a potential treatment modality for breast cancer therapy. This study provides insight into the tumor cell targeting mechanism using PBA functionalization, and the anticancer efficacy of curcumin-loaded pH-sensitive nanohybrids can be attributed to the differential oxidative stress-inducing properties of curcumin and Zn+2 ions.

8.
Toxicol Rep ; 6: 176-185, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30809470

RESUMO

In the present study, we report the microwave-induced synthesis of fluorescent zinc oxide nanorods (ZnO) and their usage as a cargo material to carry hydrophobic drug, quercetin. TEM and SEM showed the rod-shape morphology of our synthesized ZnO. XRD showed several diffraction peaks correspond to a hexagonal wurtzite structure. The optical and chemical natures of these nanorods were also confirmed from the UV-vis (showed a distinct absorption bands from 361 to 395 nm) and FTIR spectrum (showed absorption band specific to Zn-O stretching). The synthesized ZnO also showed fluorescence emission at around 550 nm when excited under UV irradiation. Quercetin was loaded onto ZnO surface via employing a metal ion-ligand coordination bond, (ZnO/QR), which exhibit pH-sensitive release behavior. ZnO/QR displayed superior drug loading content (42%) and loading efficiency (72.4%). in vitro assays showed that ZnO/QR exhibited higher anticancer, as well as antibacterial activities compared with free quercetin and ZnO. All these results highlight the synthesis of ZnO nanorods under microwave irradiation, which can be used as a plausible therapeutic option for bioimaging and drug delivery purpose.

9.
Theranostics ; 7(19): 4735-4752, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29187900

RESUMO

Rationale: Dimethyl sulfoxide (DMSO) is commonly used as a solvent for water-insoluble substances, a vehicle for drug therapy, and a cryoprotectant for cultured cells. DMSO induced embryonic defects and its mechanism of action remains unclear. The rationale is based on the assumption that DMSO supplementation should induce long-term negative effects on both pre- and post-implantation embryo development. Methods: DMSO induced oxidative stress, ER stress, autophagy, mitophagy, signaling responsible genes and proteins were determined by RT-qPCR, Western blotting, immunofluorescence, and confocal microscopy. DMSO induced mitochondrial dysfunction was measured by transmission electron microcopy and JC-1 assay. Apoptosis was estimated using TUNEL and comet assay. Post-implantation embryo developmental capability was estimated by implantation site and fetus numbers. Results: Exposure to DMSO induced an early oxidative stress response within 0.5 to 2 h in 1-cell zygotes by disrupting the balance of pro- and anti-oxidants. Notably, DMSO-treated 2-cell embryos showed increased expression of unfolded protein response genes such as Hspa5, Hsp90b1, Ddit3, Atf4, and Xbp1. As a result, the development of many embryos is arrested at the 2-cell, 4-cell, or morula stages in a dose-dependent manner. Further, DMSO-induced endoplasmic reticulum stress increased mitochondrial Ca2+ levels, induced mitochondrial depolarization/dysfunction, and induced apoptotic cell death via the JNK/ATF2-dependent pathway. Consequently, treatment with DMSO increased the expression of autophagy initiation-, phagophore elongation-, and autophagosome formation-related genes, as well as localization of PINK1/Parkin, which are the main mediators of mitophagy, in mitochondria. Interestingly, DMSO causes cytotoxic effects in preimplantation embryos by inducing extensive mitophagy and autophagy. Especially, DMSO treatment decreased the inner cell mass and trophectoderm cell numbers as well as mRNA expression of B3gnt5 and Wnt3a in developed blastocysts, which decreased the implantation and developmental rates of full-term offspring after being transferred into pseudopregnant mice. Conclusion: These results provide a significant contribution to finding effective protective agents to combat DMSO mediated reproductive toxicity for application in human embryos in the near future.


Assuntos
Blastocisto/efeitos dos fármacos , Crioprotetores/toxicidade , Dimetil Sulfóxido/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacos , Animais , Apoptose , Autofagia , Blastocisto/metabolismo , Cálcio/metabolismo , Células Cultivadas , Feminino , Camundongos , Dinâmica Mitocondrial , Estresse Oxidativo , Resposta a Proteínas não Dobradas
10.
Indian Pediatr ; 54(9): 778-780, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28984261

RESUMO

This observational, descriptive study was conducted on 260 dengue patients diagnosed as per the revised 2009 WHO guidelines in a tertiary-care hospital of eastern India between June and November 2015. Children were evaluated for clinical symptoms, signs, and laboratory parameters. Clinical variables viz., rash, nausea/vomiting, bleeding, oliguria, capillary leak and liver enlargement; and laboratory variables viz., rising haemoglobin, haematocrit, thrombocytopenia, blood urea, serum Creatinine, ALT, hypo albuminemia and cholesterol were found to be significantly associated with outcome.


Assuntos
Dengue , Adolescente , Criança , Pré-Escolar , Dengue/complicações , Dengue/epidemiologia , Dengue/mortalidade , Exantema , Hemorragia , Humanos , Índia/epidemiologia , Lactente , Náusea , Fatores de Risco
11.
J Conserv Dent ; 20(2): 86-90, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28855753

RESUMO

BACKGROUND: Endodontically treated teeth often lack sufficient support for a permanent restoration. During post space preparation, it is important not to disturb the integrity of the apical seal. AIM: This study compared the effect of immediate versus delayed post space preparation on the apical seal using four different sealers. MATERIALS AND METHODS: One hundred and thirty single rooted teeth were biomechanically prepared and obturated with single cone gutta-percha and 4 sealers: Endoflas FS, AH Plus, Gutta flow and MTA. Teeth were divided randomly into eight groups, post spaces were prepared using Gates Glidden drills immediately for group I, III, IV and VII. For groups II, IV, VI and VIII prepared after storage of the specimens in 100% humidity for one week. The samples were kept in methylene blue dye, centrifuged at 3000 rpm for 3 min sectioned and then measured under stereomicroscope for apical leakage. STATISTICAL ANALYSIS: The data was analysed using one way ANOVA and post hoc Tukey test. RESULTS: All the specimens showed dye leakage, and a statistically significant difference was seen among all the groups (P > 0.05) except Gutta flow. CONCLUSION: Less leakage is seen when post space is prepared immediately.

12.
Sci Rep ; 7(1): 9513, 2017 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-28842609

RESUMO

Nanocarriers are widely used for effective delivery of anticancer drugs to tumours with potential to improve cancer treatment. Here, we developed a nanoceria (CeO2)-based system for delivery of the anti-cancer drug doxorubicin (DOX) to human ovarian cancer cells. Negatively charged nanoceria could conjugate with the cationic DOX via electrostatic interaction under physiological conditions, forming DOX-loaded nanoceria (CeO2/DOX). CeO2/DOX particles displayed nearly spherical shapes, along with superior drug-loading content (22.41%), loading efficiency (99.51%), and higher cellular uptake and drug release behaviours compared to free DOX. Moreover, DOX was released faster from CeO2/DOX under reductive acidic conditions (pH 5.0, 10 mM glutathione) than under physiological conditions (pH 7.4). The initial intracellular DOX concentration was higher in the free DOX groups than in the CeO2/DOX groups, but quickly reduced to 25% of the initial concentration after 24-h culture. By contrast, CeO2/DOX showed sustained DOX release over time and maintained a high intracellular DOX concentration for up to 72 h. In vitro assays showed that CeO2/DOX exhibited higher cell proliferation inhibition and apoptosis compared with free DOX. These results highlight DOX-loaded nanoceria as a promising therapeutic agent for cancer treatment.


Assuntos
Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Portadores de Fármacos , Nanopartículas , Animais , Linhagem Celular Tumoral , Cério/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Feminino , Humanos , Nanopartículas/química , Nanopartículas/ultraestrutura , Neoplasias Ovarianas
13.
Sci Rep ; 7(1): 8365, 2017 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-28827731

RESUMO

Many diseases, including myocardial infarction, autoimmune disease, viral diseases, neurodegenerative diseases, and cancers, are frequently diagnosed with aberrant expression of microRNAs (miRNAs) and their allied pathways. This indicates the crucial role of miRNAs in maintaining biological and physiological processes. miR-7641 is a miRNA whose role in disease has not been fully investigated. In the present study, we investigated the expression pattern of miR-7641 and its target genes in different cancer cells, as well as in clinical cancer patients. Our data confirmed RPS16 and TNFSF10 as two direct targets of miR-7641, while gene expression study showed that a group of genes are also deregulated by miR-7641, including many ribosomal proteins that are frequently co-expressed with RPS16 in breast cancer. Direct inhibition of miR-7641 using a locked nucleic acid upregulated the expression of its target genes, sensitized cancer cells, and enhanced the efficiency of therapeutic agents such as doxorubicin. In addition, inhibition of miR-7641 boosted doxorubicin-mediated apoptosis of cancer cells via upregulation of apoptotic molecules Caspase 9 (CAS9) and poly ADP ribose polymerase (PARP) and downregulation of anti-apoptotic molecule BCL2. Thus, miR-7641 might be a clinically important cancer biomarker. Inhibition of miR-7641 expression could be an efficient treatment strategy for clinical patients.


Assuntos
Regulação da Expressão Gênica , MicroRNAs/metabolismo , Neoplasias/patologia , Proteínas Ribossômicas/biossíntese , Ligante Indutor de Apoptose Relacionado a TNF/biossíntese , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Células Epiteliais/efeitos dos fármacos , Humanos , MicroRNAs/antagonistas & inibidores
15.
Sci Rep ; 6: 33784, 2016 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-27677463

RESUMO

The controlled differentiation of stem cells via the delivery of specific genes encoding appropriate differentiation factors may provide useful models for regenerative medicine and aid in developing therapies for human patients. However, the majority of non-viral vectors are not efficient enough to manipulate difficult-to-transfect adult human stem cells in vitro. Herein, we report the first use of 25 kDa branched polyethylenimine-entrapped gold nanoparticles (AuPEINPs) and covalently bound polyethylenimine-gold nanoparticles (AuMUAPEINPs) as carriers for efficient gene delivery into human mesenchymal stem cells (hMSCs). We determined a functional application of these nanoparticles by transfecting hMSCs with the C/EBP beta gene, fused to EGFP, to induce adipogenic differentiation. Transfection efficacy with AuPEINPs and AuMUAPEINPs was 52.3% and 40.7%, respectively, which was 2.48 and 1.93 times higher than that by using Lipofectamine 2000. Luciferase assay results also demonstrated improved gene transfection efficiency of AuPEINPs/AuMUAPEINPs over Lipofectamine 2000 and polyethylenimine. Overexpression of exogenous C/EBP beta significantly enhanced adipogenesis in hMSCs as indicated by both of Oil Red O staining and mRNA expression analyses. Nanoparticle/DNA complexes exhibited favorable cytocompatibility in hMSCs. Taken together, AuPEINPs and AuMUAPEINPs potentially represent safe and highly efficient vehicles for gene delivery to control hMSC differentiation and for therapeutic gene delivery applications.

16.
Hum Reprod Update ; 22(5): 588-619, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27385359

RESUMO

BACKGROUND: Engineered nanoparticles (ENPs) offer technological advantages for a variety of industrial and consumer products as well as show promise for biomedical applications. Recent progress in the field of nanotechnology has led to increased exposure to nanoparticles by humans. To date, little is known about the adverse effects of these ENPs on reproductive health, although interest in nanotechnology area is growing. A few biocompatible ENPs have a high loading capacity for exogenous substances, including drugs, DNA or proteins, and can selectively deliver molecular cargo into cells; however, they represent a potential tool for gene delivery into gametes and embryos. OBJECTIVE AND RATIONALE: Understanding the reprotoxicological aspects of these ENPs is of the utmost importance to reliably estimate its potential impact on human health. In addition, a search for protective agents to combat ENP-mediated reproductive toxicity is warranted. Therefore, in this review we summarize the toxic effects of a few ENPs (metal and metal oxides, carbon-based nanoparticles, quantum dots and chitosan) in mammalian germ cells and developing embryos, and propose some treatment strategies that could mitigate nanoparticle-mediated toxicity. In addition, we outline the anticipated applications of ENPs in transgenic animal production in order to generate models for investigations into the mechanisms for human disease. SEARCH METHODS: A literature search was performed using the National Center for Biotechnology Information PubMed database up until March 2016 and relevant keywords were used to obtain information regarding mammalian germ cell-specific toxicity and embryotoxicity of ENPs, possible treatment strategies, as well as the anticipated applications of nanoparticles in gene delivery in germ cells and embryos. Only English language publications were included. OUTCOMES: Here, we demonstrate the toxicological effects of ENPs in mammalian germ cells and developing embryos by considering both in vitro and in vivo experimental models based on the existing literature. The biodistribution and cellular uptake of ENPs and the observed toxicities are mostly dependent on ENP size and surface-coating agents (surface functional groups/surface charge). ENPs have been shown to induce toxicity via oxidative stress, inflammation and DNA damage in both human and mouse germ cells. Use of antioxidant, anti-inflammatory drugs and selective metal chelators would be beneficial against nanoparticle-induced toxicity. WIDER IMPLICATIONS: Our review provides the reproductive scientists a mechanistic insight into the reprotoxicological aspects of ENPs to reliably estimate its potential impact on human health and help to select/design protective agents to combat ENP-mediated toxicity. Furthermore, research regarding the detailed mechanism(s) of ENP toxicity in mammalian germ cells and developing embryos as well as the search for protective agents to combat ENP-mediated reproductive toxicity is warranted. Furthermore, we anticipate that investigations into the possibility of applying nanovectors to gene delivery in germ cells and early embryos will open new horizons in reproductive biology.


Assuntos
Desenvolvimento Embrionário , Técnicas de Transferência de Genes , Células Germinativas , Nanopartículas/toxicidade , Técnicas de Reprodução Assistida , Animais , Humanos , Estresse Oxidativo
17.
Sci Rep ; 6: 29197, 2016 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-27380727

RESUMO

Gene therapy is a promising technique for the treatment of various diseases. The development of minimally toxic and highly efficient non-viral gene delivery vectors is the most challenging undertaking in the field of gene therapy. Here, we developed dimethyldioctadecylammonium bromide (DODAB)-nanoceria (CeO2) hybrids as a new class of non-viral gene delivery vectors. These DODAB-modified CeO2 nanoparticles (CeO2/DODAB) could effectively compact the pDNA, allowing for highly efficient gene transfection into the selected cell lines. The CeO2/DODAB nanovectors were also found to be non-toxic and did not induce ROS formation as well as any stress responsive and pro-survival signaling pathways. The overall vector performance of CeO2/DODAB nanohybrids was comparable with lipofectamine and DOTAP, and higher than calcium phosphate and DEAE-dextran for transfecting small plasmids. The increased cellular uptake of the nanovector/DNA complexes through clathrin- and caveolae-mediated endocytosis and subsequent release from the endosomes further support the increased gene transfection efficiency of the CeO2/DODAB vectors. Besides, CeO2/DODAB nanovectors could transfect genes in vivo without any sign of toxicity. Taken together, this new nano-vector has the potential to be used for gene delivery in biomedical applications.


Assuntos
Cério/química , Endocitose , Técnicas de Transferência de Genes , Lipídeos/química , Nanopartículas/química , Cátions , Linhagem Celular Tumoral , DEAE-Dextrano , DNA/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Hidrodinâmica , Tamanho da Partícula , Plasmídeos/metabolismo , Compostos de Amônio Quaternário , Espectrometria por Raios X , Espectroscopia de Infravermelho com Transformada de Fourier , Transfecção
18.
Sci Rep ; 6: 21688, 2016 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-26867977

RESUMO

Solid tumors are frequently associated with resistance to chemotherapy because the fraction of hypoxic tumor cells is substantial. To understand the underlying mechanism of hypoxia on silver nanoparticle (AgNPs)-induced apoptosis, the expression of hypoxia-inducible factor (HIF)-1α, a hallmark of hypoxia, was measured in the presence and absence of AgNPs. The results showed that HIF-1α expression was upregulated after AgNPs treatment under both hypoxic and normoxic conditions. Cell viability assays showed that AgNPs promoted cell death in cancer cells but not in non-cancer cells, as cancer cells are slightly more acidic than normal cells. However, reactive oxygen species generation induced by AgNPs in lung cancer cells caused high susceptibility to oxidative stress, whereas pre-exposure to hypoxia blocked AgNPs-induced oxidative stress. Notably, HIF-1α inhibited AgNPs-induced mitochondria-mediated apoptosis by regulating autophagic flux through the regulation of ATG5, LC3-II, and p62. Further, cell viability after treatment of cancer cells with AgNPs under hypoxic conditions was lower in HIF-1α siRNA-transfected cells than in control siRNA-transfected cells, indicating that HIF-1α knockdown enhances hypoxia induced decrease in cell viability. Our results suggest that hypoxia-mediated autophagy may be a mechanism for the resistance of AgNPs-induced apoptosis and that strategies targeting HIF-1α may be used for cancer therapy.


Assuntos
Antineoplásicos/toxicidade , Apoptose , Autofagia , Hipóxia Celular , Neoplasias Pulmonares/fisiopatologia , Nanopartículas/toxicidade , Prata/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Resistência a Medicamentos , Perfilação da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/análise
19.
Toxicol Ind Health ; 32(9): 1700-10, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25903088

RESUMO

Hexavalent chromium (Cr(VI)) is an environmental contaminant that is associated with reproductive abnormalities in both humans and animals. In the present study, we evaluated the cytotoxic effect of Cr(VI) on sperm function and subsequent embryo development after in vitro fertilization (IVF). Sperm obtained from BDF1 male mice were treated with potassium dichromate (0, 3.125, 6.25, 12.5, 25, or 50 µM) for 3 h. Cr(VI) significantly decreased sperm viability and acrosome reaction with increasing dose. These Cr(VI)-treated sperms were further used for IVF of oocytes obtained from BDF1 female mice. Results showed that Cr(VI)-treated sperm caused a significant reduction in IVF success, higher developmental arrest at the two-cell stage of embryos, and delayed blastocyst formation with increasing dose. In particular, most blastocysts from the Cr(VI)-treated sperm resulted in hatching failure as well as decreased inner cell mass and trophectoderm (TE). Furthermore, blastocysts obtained from Cr(VI)-treated sperm showed lower expression of not only TE-associated genes (eomes, cdx2, and krt8) but also pluripotent marker genes (sox2, pou5f1, and klf4) that are responsible for further embryo development of blastocyst embryos. The results of our current study showed that Cr(VI)-treated sperm had negative effects on oocyte fertilization and subsequent embryo development.


Assuntos
Carcinógenos Ambientais/toxicidade , Cromo/toxicidade , Ectogênese/efeitos dos fármacos , Fertilização In Vitro/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Teratogênios/toxicidade , Reação Acrossômica/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Blastocisto/efeitos dos fármacos , Blastocisto/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cultura Embrionária , Feminino , Masculino , Camundongos , Concentração Osmolar , Dicromato de Potássio/toxicidade , Espermatozoides/citologia
20.
Nanotoxicology ; 10(3): 361-73, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26470004

RESUMO

Silver nanoparticles (AgNPs) are widely used as an antibiotic agent in textiles, wound dressings, medical devices, and appliances such as refrigerators and washing machines. The increasing use of AgNPs has raised concerns about their potential risks to human health. Therefore, this study was aimed to determine the impact of AgNPs in germ cell specific complications in mice. The administration of AgNPs results in toxicity in mice; however, a more detailed understanding of the effects of AgNPs on germ cells remains poorly understood. Here, we demonstrate the effects of AgNPs (20 nm in diameter) in a mouse Sertoli and granulosa cells in vitro, and in male and female mice in vivo. Soluble silver ion (Ag(+))-treated cells were used as a positive control. We found that excessive AgNP-treated cells exhibited cytotoxicity, the formation of autophagosomes and autolysosomes in Sertoli cells. Furthermore, an increase in mitochondrial-mediated apoptosis by cytochrome c release from mitochondria due to translocation of Bax to mitochondria was observed. In in vivo studies, the expression of pro-inflammatory cytokines, including tumor necrosis factor α, interferon-γ, -6, -1ß, and monocyte chemoattractant protein-1 were significantly increased (p < 0.05). Histopathological analysis of AgNP-treated mice shows that a significant loss of male and female germ cells. Taken together, these data suggest that AgNPs with an average size of 20 nm have negative impact on the reproduction.


Assuntos
Células Germinativas/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Prata/toxicidade , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Fertilidade/efeitos dos fármacos , Células Germinativas/citologia , Células Germinativas/metabolismo , Marcação In Situ das Extremidades Cortadas , Mediadores da Inflamação/metabolismo , Lisossomos/efeitos dos fármacos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Nanopartículas Metálicas/química , Camundongos , Ovário/citologia , Ovário/efeitos dos fármacos , Fagossomos/efeitos dos fármacos , Prata/química , Espermatogênese/efeitos dos fármacos , Testículo/citologia , Testículo/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA