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1.
Appl Microbiol Biotechnol ; 105(7): 2615-2624, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33710356

RESUMO

A most discussed topic of the new decade, COVID-19 is an infectious disease caused by the recently discovered SARS-CoV-2. With an exceedingly high transmission rate, COVID-19 has affected almost all the countries in the world. Absent any vaccine or specific treatment, the humanity is left with nothing but the legacy method of quarantine. However, quarantine can only be effective when combined with early diagnosis of suspected cases. With their high sensitivity and unmatched specificity, biosensors have become an area of interest for development of novel diagnostic methods. Compared to the more traditional diagnostics, nanobiotechnology introduces biosensors as different diagnostics with greater versatility in application. Today, a growing number of analytes are being accurately identified by these nanoscopic sensing machines. Several reports of validated application with real samples further strengthen this idea. As of recent, there has been a rise in the number of studies on portable biosensors. Despite the slow progression, certain devices with embedded biosensors have managed to be of diagnostic value in several countries. The perceptible increase in development of mobile platforms has revolutionized the healthcare delivery system in the new millennium. The present article reviews the most recent advancements in development of diagnostic nanobiosensors and their application in the clinical fields. KEY POINTS: • There is no specific treatment for highly transmissible SARS-CoV-2. • Early diagnosis is critical for control of pandemic. • Highly sensitive/specific nanobiosensors are emerging assets against COVID-19.


Assuntos
Técnicas Biossensoriais/métodos , COVID-19/diagnóstico , Diagnóstico Precoce , SARS-CoV-2 , Técnicas Biossensoriais/instrumentação , Humanos , Técnicas de Diagnóstico Molecular , Nanotecnologia , Técnicas de Amplificação de Ácido Nucleico , SARS-CoV-2/isolamento & purificação
2.
Artigo em Inglês | MEDLINE | ID: mdl-32679016

RESUMO

BACKGROUND: Sulfur-(SM) and nitrogen (NM)-based mustards are the mutagenic incapacitating compounds which are widely used in vesicating the chemical warfare and cause toxicity in many organs, especially skin. SM, as a potent vesicating agent, contributes to the destruction of skin in dermis and epidermis layers. The progression of the lesion depends on the concentration of SM and the duration of exposure. Body responses start with pruritus, erythema, edema and xerosis, which lead to the accumulation of immune cells in the target sites and recruitment of mast cells and paracrine-mediated activity. Pro-inflammatory effectors are accumulated in the epidermis, hair follicles, and sebaceous glands resulting in the destruction of the basement membrane beneath the epidermis. There is still no satisfactory countermeasure against SM-induced lesions in clinical therapy, and the symptomatic or supportive treatments are routine management approaches. OBJECTIVE: The current review highlights the recent progression of herbal medicines application in SM-induced injuries through the illustrative examples and also demonstrates their efficacies, properties and mechanism of actions as therapeutic agents. CONCLUSION: Phytochemicals and herbal extracts with anti-bacterial, anti-inflammatory and antioxidant properties have been recently shown to hold therapeutic promise against the SM-induced cutaneous complications. The present review discusses the possible application of herbal medicines in the healing of SM-induced injuries.


Assuntos
Gás de Mostarda/química , Compostos Fitoquímicos/química , Extratos Vegetais/química , Plantas Medicinais/química , Enxofre/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Depuradores de Gases , Medicina Herbária , Humanos , Gás de Mostarda/farmacologia , Nitrogênio/química , Nitrogênio/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Pele , Enxofre/farmacologia , Cicatrização/efeitos dos fármacos
3.
Mater Sci Eng C Mater Biol Appl ; 118: 111384, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33254991

RESUMO

Temperature-responsive drug-loaded electrospun nanofibers have gained huge critical attention as efficient localized implantable devices in preventing cancer local recurrence. In this regard, a smart hyperthermia nanofiber with the simultaneous heat-generation and dual-stage drug release ability in response to 'ON-OFF' switching of an alternating magnetic field (AMF) for improved hyperthermic chemotherapy has been developed. The smart hyperthermia nanofibrous scaffolds are fabricated via electrospinning a temperature-responsive copolymer blended with iron oxide (II, III) magnetic nanoparticles (MNPs, 10 nm), metformin (MET), and mesoporous silica nanoparticles (MSNs) loaded with MET (MSNs@MET). It was found that all the magnetic nanofibers (MNFs) possess heat generation property and 'ON-OFF' switchable heating ability. The swelling ratio with reversible alterations and the corresponding drug discharge in response to AMF application with 'ON-OFF' switching was also demonstrated. MET-MNFs showed an initial rapid discharge in the 1st cycle of AMF application while MET released from MET@MSNs-MNFs exhibited a sustained release without the initial rapid discharge. It was found that MET-MET@MSNs-MNFs displayed a blend of initial rapid discharge and late prolonged drug discharge. In a magnetic field for 300 s during the second and third days, the metabolic activity of B16F10 skin melanoma cells incubated with all types of MNFs was decreased. Importantly, MET-MET@MSNs-MNFs had enhanced cytotoxicity than the MET-MNFs and MET@MSNs-MNFs (P < .05), due to the double effects of heat and dual-stage drug release. These results demonstrated that the proposed two-stage drug discharge approach plus hyperthermia is more desirable to standard chemotherapy regimens and might effectively induce cytotoxicity via a synergistic effect over a relatively long time.


Assuntos
Hipertermia Induzida , Nanofibras , Nanopartículas , Neoplasias , Liberação Controlada de Fármacos , Humanos , Hipertermia , Dióxido de Silício
4.
J Control Release ; 330: 1046-1070, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33188829

RESUMO

Short interfering RNAs (siRNAs), as small non-coding RNA fragments, are one of the widely studied RNAi inducers for gene modulations. The reasonably designed siRNA probes provide a novel potential therapeutic strategy for cancer therapy via silencing the specific cancer-promoting gene. The optimization of physicochemical properties of delivery vectors, such as stability, the possibility of surface functionalization, size, charge, biocompatibility, biodegradability, and non-immunogenicity with receptor-mediated targeting ligands, is necessary for effective intracellular siRNA delivery. The present review is focused on the recent progress of the non-viral nanocarriers for siRNA cancer treatment based on synthetic approaches associated with cyclodextrin (CD)-based carbohydrate polymers, i.e. CD-cationic polymers, CD-polyrotaxanes, CD-dendrimers, and CD-modified tumor-specific targeting ligands. Besides, the efficiency of nanocarriers-based stimuli-responsive CDs is described for the simultaneous delivery of siRNAs and chemotherapeutic drugs. Further, theranostic CD compounds are introduced for the specific diagnosis and cargo-targeting delivery to the specific disease sites. In the meantime, the development of the inherent fluorescent CD-based supramolecular biomaterials without formal chromophores will open up a new strategy to design an effective theranostic non-viral carrier system.


Assuntos
Ciclodextrinas , Neoplasias , Rotaxanos , Genes Neoplásicos , Neoplasias/terapia , Polímeros , RNA Interferente Pequeno
5.
Mater Sci Eng C Mater Biol Appl ; 116: 111225, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32806312

RESUMO

Zeolites are crystalline, hydrated aluminosilicates of alkali earth cations, consisting of 3D frameworks of [SiO4]4- and [AlO4]5- tetrahedral, linked through the shared oxygen atoms, which have been widely applied in multifarious technological approaches such as adsorbents, catalysts, ion exchangers, molecular sieves for separation, and sorting the molecules according to their crystalline size dimensions. On the other hand, the unique and outstanding physical and chemical properties of zeolite materials such as porous character, ion exchangeability, water absorption capacity, immunomodulatory and antioxidative effects, biocompatibility and long-term chemical and biological stability, make them increasingly useful in various filed of biomedicine including drug delivery systems, wound healing, scaffolds used in tissue engineering, anti-bacterial and anti-microbial, implant coating, contrast agents, harmful ions removal from the body, gas absorber, hemodialysis, and teeth root filling. Therefore, this review focuses on the more recent advances of the use of zeolites in various biomedical applications feedbacks especially drug delivery, regenerative medicine, and tissue engineering with special emphasis on their biomaterial perspectives.


Assuntos
Zeolitas , Materiais Biocompatíveis , Sistemas de Liberação de Medicamentos , Medicina Regenerativa , Engenharia Tecidual
6.
Int J Pharm ; 587: 119656, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32687972

RESUMO

The present research aims to design and develop a sustained drug release system to support the long-term proliferation of human adipose-derived stem cells (hADSCs) without losing their stemness and entering the cellular senescence through providing typical cell culture conditions. For this purpose, Curcumin-loaded mesoporous silica nanoparticles (CUR@MSNs) incorporated into Poly-ε-Caprolactone/Gelatin (PCL/GEL) hybrid were prepared via blend electrospinning and their impact was evaluated on cell adhesion, viability, proliferation and also the expression of senescence markers and stemness genes after a long-term in vitro culturing. The in vitro release findings proved that the MSNs incorporated into the electrospun nanofibers (NFs) allowed a sustained release of CUR. According to MTT and PicoGreen assays, the significant metabolic activity and proliferation of hADSCs were detected on CUR@MSNs-NFs after 14 and 28 days of incubation. Furthermore, CUR@MSNs-NFs showed better adhesion and spreading of hADSCs compared to other types of NFs. The sustained and prolonged delivery of CUR inhibited the stem cell senescence through the down-regulation of p16INK4A and up-regulation of hTERT. It also led to an increased stemness potency in growing hADSCs on the fibers. These results confirmed that the nanofiber-based sustained drug delivery system might provide a promising approach in designing highly programmable culture platforms to generate sufficient numbers of biologically functional hADSCs for clinical translation.


Assuntos
Curcumina , Nanofibras , Nanopartículas , Proliferação de Células , Humanos , Dióxido de Silício , Células-Tronco
7.
J Cell Physiol ; 235(12): 8873-8924, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32452539

RESUMO

Months after the outbreak of a new flu-like disease in China, the entire world is now in a state of caution. The subsequent less-anticipated propagation of the novel coronavirus disease, formally known as COVID-19, not only made it to headlines by an overwhelmingly high transmission rate and fatality reports, but also raised an alarm for the medical community all around the globe. Since the causative agent, SARS-CoV-2, is a recently discovered species, there is no specific medicine for downright treatment of the infection. This has led to an unprecedented societal fear of the newly born disease, adding a psychological aspect to the physical manifestation of the virus. Herein, the COVID-19 structure, epidemiology, pathogenesis, etiology, diagnosis, and therapy have been reviewed.


Assuntos
Betacoronavirus/patogenicidade , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Sistema Imunitário/virologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Betacoronavirus/imunologia , COVID-19 , Teste para COVID-19 , China/epidemiologia , Infecções por Coronavirus/virologia , Humanos , Pandemias , Pneumonia Viral/virologia , Sistema Respiratório/virologia , SARS-CoV-2
8.
J Biomed Mater Res A ; 108(7): 1444-1458, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32246745

RESUMO

Nanotechnology empowered localized cancer chemotherapy has indicated a promising performance for targeting and controlled release of anticancer agents over a period of time to eliminate local-regional recurrence of cancers and also to improve the tissue regeneration during/after treatment. Electrospun nanofiber-based implantable drug-delivery systems have been established as one of the most effective approaches for localized cancer treatment, allowing the on-site delivery of anticancer agents and reducing systemic toxicities and side effects to normal cells. The present review aimed to summarize the latest cutting-edge research on applications of electrospun-based systems for local chemotherapy. Meantime, in vitro and in vivo studies conducted using various anticancer agents along with the capability of electrospun nanofibers for combinatorial/synergistic chemotherapy as well as existing challenges and the potential dramatic advances in applying this pioneering approach for clinical transition in localized treatments of cancer is also discussed.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Nanofibras/química , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Preparações de Ação Retardada/química , Humanos , Nanotecnologia/métodos
9.
Curr Mol Med ; 20(1): 13-35, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31573884

RESUMO

In both men and women around the world, lung cancer accounts as the principal cause of cancer-related death after breast cancer. Therefore, early detection of the disease is a cardinal step in improving prognosis and survival of patients. Today, the newly-defined microRNAs regulate about 30 to 60 percent of the gene expression. Changes in microRNA Profiles are linked to numerous health conditions, making them sophisticated biomarkers for timely, if not early, detection of cancer. Though evaluation of microRNAs in real samples has proved to be rather challenging, which is largely attributable to the unique characteristics of these molecules. Short length, sequence similarity, and low concentration stand among the factors that define microRNAs. Recently, diagnostic technologies with a focus on wide-scale point of care have recently garnered attention as great candidates for early diagnosis of cancer. Electrochemical nano-biosensors have recently garnered much attention as a molecular method, showing great potential in terms of sensitivity, specificity and reproducibility, and last but not least, adaptability to point-of-care testing. Application of nanoscale materials in electrochemical devices as promising as it is, brings multiplexing potential for conducting simultaneous evaluations on multiple cancer biomarkers. Thanks to their enthralling properties, these materials can be used to improve the efficiency of cancer diagnostics, offer more accurate predictions of prognosis, and monitor response to therapy in a more efficacious way. This article presents a concise overview of recent advances in the expeditiously evolving area of electrochemical biosensors for microRNA detection in lung cancer.


Assuntos
Biomarcadores Tumorais/isolamento & purificação , Técnicas Biossensoriais , Neoplasias Pulmonares/diagnóstico , MicroRNAs/isolamento & purificação , Biomarcadores Tumorais/genética , Técnicas Eletroquímicas , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Nanopartículas/química
10.
Mater Sci Eng C Mater Biol Appl ; 104: 110007, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31500008

RESUMO

MicroRNAs are types of small single-stranded endogenous highly conserved non-coding RNAs, which play main regulatory functions in a wide range of cellular and physiological events, such as proliferation, differentiation, neoplastic transformation, and cell regeneration. Recent findings have proved a close association between microRNAs expression and the development of many diseases, indicating the importance of microRNAs as clinical biomarkers and targets for drug discovery. However, due to a number of prominent characteristics like small size, high sequence similarity and low abundance, sensitive and selective identification of microRNAs has rather been a hardship through routine traditional assays, including quantitative polymerase chain reaction, microarrays, and northern blotting analysis. More recently, the soaring progression in nanotechnology and fluorimetric methodologies in combination with nanomaterials have promised microRNAs detection with high sensitivity, efficiency and selectivity, excellent reproducibility and lower cost. Therefore, this review will represent an overview of latest advances in microRNAs detection through nanomaterials-based fluorescent methods, like gold nanoparticles, silver and copper nanoclusters, graphene oxide, and magnetic silicon nanoparticles.


Assuntos
MicroRNAs/química , Nanoestruturas/química , Animais , Técnicas Biossensoriais/métodos , Fluorometria/métodos , Humanos , Nanopartículas Metálicas/química , Nanotecnologia/métodos
12.
J Tehran Heart Cent ; 13(2): 58-64, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30483314

RESUMO

Background: Recently, rs9289231 genetic variations of kalirin (KALRN) have been introduced as potential genetic markers for coronary artery disease (CAD). However, the influence of KALRN single-nucleotide polymorphisms (SNPs) on serum kalirin levels has not been investigated in CAD patients so far. Thus, the present study aimed to survey whether SNP T>G (rs9289231) was associated with the risk of early-onset CAD and serum kalirin levels among the study subjects. Methods: The rs9289231 polymorphism of the KALRN was genotyped in 512 subjects (61.5% male, mean age=46.3±7.1 y), comprising 268 subjects with angiographically diagnosed CAD and 244 controls using an HRM assay. Also, the levels of serum kalirin were compared between 133 CAD subjects and 123 controls using a sandwich ELISA assay. Results: The CAD subjects had more frequently GG genotypes than the controls. The odds ratio (OR) remained significant after adjustment for known CAD risk factors (OR=4.13, 95% CI: 2.48-9.10; P<0.001). A significant difference was also observed in that the G allele was more frequent among the CAD subjects. The G allele at the rs9289231 polymorphism was associated with a higher risk of CAD (OR=2.11, 95% CI: 1.27-2.59; P=0.001). The mean kalirin level of the CAD patients was higher than that of the controls (P=0.041). No significant correlation was seen in the different genotypes with serum kalirin levels. Conclusion: The KALRN rs9289231 T>G variant was considerably related with an increased risk of early-onset CAD. High kalirin levels were found in young CAD patients compared to the control subjects, with the levels not affected by the different genotypes of rs9289231.

13.
Iran J Basic Med Sci ; 21(11): 1167-1173, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30483391

RESUMO

OBJECTIVES: Breast cancer remains a global challenge, and further chemopreventive therapies are still immediately required. Emerging evidence has revealed the potent anti-cancer effects of biguanides, Metformin (MET) and phenformin (PHE). Thus, to explore an efficient chemopreventive strategy for breast cancer, the antiproliferative effects of the combination of MET and PHE against breast cancer cells were assessed. MATERIALS AND METHODS: Cytotoxicity of the drugs individually and in combination against T47D and MDA-MB-231 breast cancer cells were assessed using MTT assay and the median-effect method was used to analyze the precise nature of the interaction between MET and PHE. Besides, the expression levels of hTERT after 48 hr drug exposure were determined using qRT-PCR. RESULTS: Based on the cytotoxicity assay, both MET and PHE further inhibited the growth of MDA-MB-231 cells compared with T47D cells. It was found that MET+PHE reduced the IC50s of MET and PHE in both cells drastically more than the single treatments in a synergistic manner. Importantly, MET+PHE showed higher antiproliferative effect with smaller IC50 values against MDA-MB-231 cells than against T47D cells. Real-time PCR results revealed that hTERT expression was significantly reduced in both breast cancer cell lines treated with MET+PHE than the single treatments. In comparison between two types of breast cancer cells, it was detected that MET+PHE could further decline hTERT expression in MDA-MB-231cells than in T47D cells (P<0.001). CONCLUSION: It is speculated that the combination of MET and PHE may be a promising and convenient approach to improve the efficiency of breast cancer treatment.speculated that the combination of MET and PHE may be a promising and convenient approach to improve the efficiency of breast cancer treatment.

14.
Mater Sci Eng C Mater Biol Appl ; 92: 902-912, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30184820

RESUMO

Herbs having various natural substances can be utilized for the biosynthesis of Silver nanoparticles (AgNPs) and act as a stable, reliable and biocompatible alternative instead of the current physical and chemical approaches. It has been reported that Matricaria chamomilla possesses unique properties, especially anti-cancerous effects. The objective of the current work was to assess the chemical characteristics and anticancer effects of biosynthesized AgNPs applying aqueous extracts of M. chamomilla against A549 lung cancer cells. UV-visible spectrum showed the maximum absorption of the biosynthesized AgNPs at 430 nm. The crystalline structure of biosynthesized AgNPs in optimal conditions was confirmed by XRD. Moreover, the presence of Ag as the ingredient element was exhibited via EDX analysis. FT-IR results also verified the AgNPs synthesis using a plant extract. The spherical shapes of the AgNPs with an average diameter size around 45.12 nm and a zeta potential value of -34 mV were characterized using DLS, and confirmed through FE-SEM and TEM. In vitro cytotoxicity assay using MTT revealed that the biosynthesized AgNPs exhibited a dose- and time- dependent cytotoxic effect against A549 lung cancer cells. Moreover, the apoptotic effects of the AgNPs were demonstrated using DAPI staining, real-time PCR and flow cytometry. According to these findings, using M. chamomilla in combination with AgNPs via green-synthesis approach may be an efficient strategy for effective treatment of lung cancer.


Assuntos
Biomimética/métodos , Matricaria/química , Nanopartículas Metálicas/química , Extratos Vegetais/química , Prata/química , Células A549 , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/prevenção & controle , Extratos Vegetais/farmacologia , Reação em Cadeia da Polimerase em Tempo Real
15.
Biomed Pharmacother ; 105: 1026-1032, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30021337

RESUMO

Up-regulation of heat shock protein 90 (HSP90) gene takes place in lung cancer cells. Therefore, targeting HSP90 in lung cancer may be promising step in lung cancer therapy. The present study aimed to evaluate the efficiency of implantable 17-dimethylaminoethylamino-17-demethoxy geldanamycin (17-DMAG)-loaded Poly(caprolactone)-poly(ethylene glycol) (PCL/PEG) nanofibers to increase the anti-cancer effects via inhibition of HSP90 expression and telomerase activity. For this purpose, 17-DMAG-loaded PCL/PEG nanofibers were successfully fabricated via electrospinning and characterized using FE-SEM and FTIR. Colorimetric MTT assay was used to determine the drug cytotoxicity. Also, the expression levels of HSP90 mRNA in the A549 cells treated with the nanofibers were assessed using Quantitative Real-Time PCR. The effect of free 17-DMAG and 17-DMAG-loaded PCL/PEG nanofiber treatment on telomerase activity was monitored by TRAP assay. MTT assay confirmed that loading of 17-DMAG into PCL/PEG nanofiber enhanced dramatically cytotoxicity in the lung cancer cells. This finding was associated with reduction of HSP90 mRNA expression and telomerase activity in the cells seeded on 17-DMAG-loaded PCL/PEG nanofibers in relative to free 17-DMAG. In conclusion, the findings demonstrated that 17-DMAG-loaded PCL/PEG nanofibers are more effectual than free 17-DMAG against A549 lung cancer cells via modulation of Hsp90 expression and inhibition of telomerase activity. Hence, the implantable 17-DMAG-loaded nanofibrous scaffolds might be an excellent tool for efficiently killing of the lung residual cancer cells and avoid the local cancer recurrence.


Assuntos
Benzoquinonas/administração & dosagem , Portadores de Fármacos/administração & dosagem , Inibidores do Crescimento/administração & dosagem , Proteínas de Choque Térmico HSP90/biossíntese , Lactamas Macrocíclicas/administração & dosagem , Neoplasias Pulmonares/metabolismo , Nanofibras/administração & dosagem , Células A549 , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos/métodos , Implantes de Medicamento , Expressão Gênica , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Humanos , Neoplasias Pulmonares/tratamento farmacológico
16.
Drug Res (Stuttg) ; 68(12): 710-716, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29920623

RESUMO

BACKGROUND: There is a growing body of data that chemotherapeutic combination strategies would be more effective in reducing drug toxicity, inhibiting tumor progression in comparison to either drug alone. OBJECTIVE: To explore a chemopreventive strategy for improving breast cancer treatment efficacy, the anticancer effects of a combination of Metformin (MET) and Silibinin (SIL) were investigated in T47D breast cancer cells. MATERIALS AND METHODS: Cytotoxicity of the drugs individually and in combination was evaluated using MTT assay. The precise nature of the interaction between MET and SIL was further analyzed through the median-effect method. In addition, qRT-PCR was applied to determine the expression levels of hTERT and cyclin D1 genes after 48 h drug exposure. RESULTS: MTT assays showed that MET and SIL individually inhibited the cell viability in a dose and time-dependent manner, and the obtained combination indices (CIs) were<1 for all the combination treatments, indicating that the anticancer agents synergistically induced growth inhibition in the breast cancer cells. qPCR findings revealed that the drug combination also synergistically down-regulated the expression levels of hTERT and cyclin D1 at all used concentrations compared with the drugs used alone after 48 h treatment (P≤0.05). CONCLUSION: The results provide evidence that synergistic antiproliferative effects of MET and SIL, linking to the down-regulation of Cyclin D1 and hTERT genes, and propose that MET+SIL may have therapeutic value in breast cancer therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/tratamento farmacológico , Ciclina D1/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Telomerase/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Feminino , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , Silibina/farmacologia , Silibina/uso terapêutico
17.
Biomed Pharmacother ; 105: 773-780, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29909345

RESUMO

The purpose of this study was to investigate the efficiency of a natural flavonoid, Chrysin (Chr), encapsulated in PLGA-PEG nanoparticles (NPs) for the modulation of macrophage polarity from the pro-inflammatory M1 to anti-inflammatory M2 phenotype. The synthetized NPs were characterized using FTIR, DLS and FE-SEM. MTT assay was used to assess the toxicity of different concentration of Chr-encapsulated NPs on LPS/IFN-γ stimulated peritoneal exudate macrophages. To investigate the repolarization efficiency of Chr-encapsulated NPs, real-time PCR was applied to measure M1 (iNOS and SOCS3) and M2 (Arg1 and Fizz) markers expression. Also, the relative mRNA and protein expression levels of pro-inflammatory cytokines including IL-6, IL-1ß and TNF-α were investigated in M1 macrophages treated with Chr-encapsulated NPs. Findings revealed that the Chr-encapsulated NPs with spherical shape and an average diameter of 235 nm were considerably less toxic to the macrophages. Additionally, the nano-formulated Chr efficiently showed a reduction in M1 markers and an increase in M2 markers levels than free Chr. Furthermore, macrophage phenotype switching by PLGA-PEG encapsulated Chr NPs significantly suppressed LPS/IFN-γ induced inflammation by a remarkable reduction in pro-inflammatory cytokine levels, TNF-α, IL-1ß, and IL-6. Convincingly, the results revealed that PLGA-PEG encapsulated Chr based drug delivery system might be introduced into biomaterials to fabricate bioactive smart multifunctional nanocomposites with macrophage repolarization activities for regenerative medicine purposes.


Assuntos
Adjuvantes Imunológicos/farmacologia , Polaridade Celular/efeitos dos fármacos , Portadores de Fármacos/química , Flavonoides/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Nanocápsulas/química , Polietilenoglicóis/química , Poliglactina 910/química , Adjuvantes Imunológicos/administração & dosagem , Animais , Polaridade Celular/imunologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/imunologia , Composição de Medicamentos , Liberação Controlada de Fármacos , Flavonoides/administração & dosagem , Regeneração Tecidual Guiada , Macrófagos Peritoneais/imunologia , Camundongos Endogâmicos C57BL , Propriedades de Superfície
18.
Artif Cells Nanomed Biotechnol ; 46(sup2): 75-86, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29607740

RESUMO

Due to the high rate of drug resistance among malignant melanoma cases, it seems necessary to introduce an efficient pharmaceutical approach to melanoma treatment. For this purpose, Curcumin (Cur) and Chrysin (Chr), two natural anti-cancers, were co-encapsulated in PLGA-PEG nanoparticles (NPs), characterized by DLS, FTIR and FE-SEM and investigated for their effects on MMPs, TIMPs and TERT genes expression in C57B16 mice bearing B16F10 melanoma tumours. The results showed that the expression of MMP-9, MMP-2 and TERT genes were significantly decreased in all treated groups compared to the control. This reduction had the highest amount in CurChr NPs group and then CurChr group for each three genes. Likewise, the expression of TIMP-1 and TIMP-2 genes was significantly increased in all treated groups, compared to the control. Combination groups showed the highest rise in expression of these two genes and the observed increase was greater in nano groups. Moreover, the highest melanoma tumour growth inhibition was detected for CurChr NPs, followed by CurChr = Cur NPs > Cur > Chr NP > Chr. Overall, it is speculated that the nano-combination of Cur and Chr into polymeric NPs with a one-step fabricated co-delivery system may be a promising and convenient approach to improve their efficiency in melanoma cancer therapy.


Assuntos
Curcumina/farmacologia , Flavonoides/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Metaloproteinases da Matriz/genética , Melanoma Experimental/patologia , Telomerase/genética , Inibidores Teciduais de Metaloproteinases/genética , Animais , Cápsulas , Proliferação de Células/efeitos dos fármacos , Curcumina/química , Modelos Animais de Doenças , Progressão da Doença , Portadores de Fármacos/química , Flavonoides/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Metástase Neoplásica , Polietilenoglicóis/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química
19.
Biomed Pharmacother ; 102: 608-617, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29602128

RESUMO

Heat shock protein 90 (Hsp90) is an evolutionary preserved molecular chaperone which mediates many cellular processes such as cell transformation, proliferation, and survival in normal and stress conditions. Hsp90 plays an important role in folding, maturation, stabilization and activation of Hsp90 client proteins which all contribute to the development, and proliferation of cancer as well as other inflammatory diseases. Functional inhibition of Hsp90 can have a massive effect on various oncogenic and inflammatory pathways, and will result in the degradation of their client proteins. This turns it into an interesting target in the treatment of different malignancies. 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) as a semi-synthetic derivative of geldanamycin, has several advantages over 17-Allylamino-17-demethoxygeldanamycin (17-AAG) such as higher water solubility, good bioavailability, reduced metabolism, and greater anti-tumour capability. 17-DMAG binds to the Hsp90, and inhibits its function which eventually results in the degradation of Hsp90 client proteins. Here, we reviewed the pre-clinical data and clinical trial data on 17-DMAG as a single agent, in combination with other agents and loaded on nanomaterials in various cancers and inflammatory diseases.


Assuntos
Benzoquinonas/uso terapêutico , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Lactamas Macrocíclicas/uso terapêutico , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Animais , Ensaios Clínicos como Assunto , Descoberta de Drogas , Proteínas de Choque Térmico HSP90/metabolismo , Humanos
20.
In Vitro Cell Dev Biol Anim ; 54(3): 205-216, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29380193

RESUMO

In recent decades, mesenchymal stem cells originated from adipose tissue (adipose-derived stem cells, ASCs) have gained increased attention for production of cell-based therapeutics. Emu oil as a natural compound showed antioxidant effects in previous studies. The goal of this study was to investigate the effect of crude emu oil on the proliferation, cell cycle progression, stemness genes expression, and in vitro wound healing potential of ASCs. An emulsion of emu oil was prepared using egg lecithin and butylated hydroxytoluene to improve bioavailability and solubility of emu oil in the expansion medium. The ASCs were treated using a series of emu oil concentrations in emulsion form, diluted in expansion medium (0.03-3 mg/ml). The emu oil-free emulsion was used as control treatment. The results revealed that emu oil (1.25 mg/ml) in emulsion form significantly (p < 0.001) increased ASCs proliferation and colony formation. Additionally, emu oil caused upregulation of stemness marker genes (Sox2, Oct4, Nanog, and Nestin) (p < 0.05). The cell cycle analysis after emu oil treatments showed an increase in the population of ASCs in S-phase of the cell cycle. Besides, an accelerated in vitro scratch wound healing was observed in emu oil-treated ASCs. Emu oil enhanced proliferation, colony formation, stemness genes expression, and in vitro wound healing of ASCs. These findings suggest that emu oil treatment could maintain the stemness of ex vivo cultivated ASCs and enhance their regenerative potential.


Assuntos
Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Lecitinas/química , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Óleos/farmacologia , Tecido Adiposo/citologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/fisiologia , Anti-Inflamatórios/farmacologia , Hidroxitolueno Butilado/química , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Emulsões , Perfilação da Expressão Gênica , Humanos , Técnicas In Vitro , Células-Tronco Mesenquimais/fisiologia , Cicatrização/efeitos dos fármacos
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