RESUMO
Neurological disorders are the leading cause of disability and the world's second leading cause of death. Despite the availability of significant knowledge to reduce the burden of some neurological disorders, various studies are exploring more effective treatment options. While the human body can repair and regenerate damaged tissue through stem cell recruitment, nerve regeneration in case of injury is minimal due to the restriction on the location of nerve stem cells. Recently, different types of stem cells extracted from various tissues have been used in combination with natural stimuli to treat neurologic disorders in neuronal tissue engineering. Flavonoids are polyphenolic compounds that can induce the differentiation of stem cells into neurons and stimulate stem cell proliferation, migration, and survival. They can also increase the secretion of nutritional factors from stem cells. In addition to the effects that flavonoids can have on stem cells, they can also have beneficial therapeutic effects on the nervous system alone. Therefore, the simultaneous use of these compounds and stem cells can multiply the therapeutic effect. In this review, we first introduce flavonoid compounds and provide background information on stem cells. We then compile available reports on the effects of flavonoids on stem cells for the treatment of neurological disorders.
Assuntos
Doenças do Sistema Nervoso , Células-Tronco Neurais , Humanos , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Neurônios , Regeneração Nervosa , Doenças do Sistema Nervoso/tratamento farmacológicoRESUMO
Acute promyelocytic leukaemia (APL) is commonly treated with arsenic trioxide (As2O3) that has many side effects. Given the increasing trend of studies on beneficial therapeutic properties of synthetic compounds containing vanadium, the present study sought to use Schiff base oxovanadium complex to reduce the needed concentration of arsenic trioxide. The HL-60 cell line, which is a model of APL, was selected and the effects of arsenic trioxide and Schiff base oxovanadium complex were individually and simultaneously evaluated on the cell viability by the MTT assay. Flow cytometry and Real-time RT-PCR were also performed to investigate the rate of apoptosis and the expression of P53 and P21 genes, respectively. The IC50 of arsenic trioxide and Schiff base oxovanadium complex on Hl-60 cells was 8.37 ± 0.36 µM and 34.12 ± 1.52 µg/ml, respectively. At the simultaneous administration of both compounds, the maximum decrease in the cell viability was seen in co-administration of 40 µg/ml of Schiff base oxovanadium complex and 0.001 µM of arsenic trioxide. Real-time RT-PCR indicated that the co-administration of Schiff base oxovanadium complex 40 µg/ml and arsenic trioxide 0.001 µM could increase the expression of P53 and P21 genes by 3.76 ± 0.19 and 6.57 ± 1.29 fold change, respectively to the control sample. The flow cytometry studies also indicated that this co-administration could induce apoptosis up to 67% ± 0.9% significantly higher than the control sample. The use of Schiff base oxovanadium complex could significantly reduce the required dose of arsenic trioxide to induce apoptosis in HL-60 cells.
Assuntos
Antineoplásicos , Arsenicais , Leucemia Promielocítica Aguda , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Trióxido de Arsênio/farmacologia , Trióxido de Arsênio/uso terapêutico , Arsenicais/farmacologia , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/metabolismo , Óxidos/farmacologia , Bases de Schiff/farmacologia , Bases de Schiff/uso terapêuticoRESUMO
D-galactose (d-gal) induces aging and memory impairment via oxidative stress and neuroinflammation pathways. This study evaluated the neuroprotective activity of thymoquinone (TQ) against d-gal. d-gal (400 mg/kg, SC), d-gal plus TQ (2.5, 5, 10 mg/kg, i.p.), and TQ alone (2.5 and 10 mg/kg) for 8 weeks were administered to rats. The effect of TQ on learning and memory were studied using the Morris water maze test. Malondialdehyde (MDA) and glutathione (GSH) levels were determined in the hippocampus. The levels of MAPKs (p-ERK/ERK, p-P38/P38), cAMP response elements binding (p-CREB/CREB), advanced glycation end products (AGEs), inflammatory markers (TNFα, IL-1ß), glial fibrillary acidic protein (GFAP), and brain-derived neurotrophic factor (BDNF) were analyzed by western blotting. Telomere length was evaluated using real-time PCR. Memory and learning impairment, MDA enhancement, GSH reduction, and neuroinflammation via increasing the TNFα, IL-1ß, and GFAP contents were observed in d-gal group. TQ with d-gal, improved memory impairment, reduced oxidative stress, and alleviated neuroinflammation. The elevated level of AGEs decreased by TQ compared to d-gal. No changes were observed in the levels of p-ERK/ERK, p-CREB/CREB, p-P38/P38, BDNF, and telomere length following administration of d-gal or TQ plus d-gal. TQ improved memory deficits of d-gal through anti-oxidative and anti-inflammatory mechanisms.
Assuntos
Benzoquinonas/química , Galactose/efeitos adversos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Masculino , Ratos , Ratos Wistar , Homeostase do TelômeroRESUMO
OBJECTIVE: The present study aimed to evaluate the effect of crocin (CRO)-loaded collagen (COL) scaffold on the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BM-MSCs). SIGNIFICANCE: Different studies have been conducted to develop an efficient strategy to accelerate and improve the recovery process of bone defects. It was shown that CRO, extracted from saffron, could induce osteogenic differentiation of rat BM-MSCs. Scaffolds can also provide a three-dimensional environment for migration, adhesion, growth, and proliferation of MSCs. METHODS: Collagen scaffolds were fabricated through freeze-drying followed by cross-linking by dehydrothermal method. Then, CRO was incorporated into the scaffolds. Physicochemical characterization of the scaffolds was evaluated. Rat BM-MSCs were seeded on CRO-loaded COL scaffolds and cultured for 14 days. Osteogenic differentiation was evaluated using alizarin red (ALZ) staining and alkaline phosphatase (ALP) activity assay and compared to the positive control group. RESULTS: The average pore size of the COL scaffolds was about 97 ± 6.7 µm. Formation of amide cross-links was confirmed by FTIR. The scaffolds were capable of uptaking water up to 50 times more than their initial dry weight and releasing above 90% of their uploaded CRO during 24 h. Collagen scaffolds containing CRO (25 and 50 µM) increased ALZ intensity (3.16 ± 0.3 and 7.32 ± 0.3 folds, respectively) and ALP activity (13.7 ± 1.1 and 12.2 ± 9.4 folds, respectively) in comparison with the positive control group. CONCLUSION: Crocin-loaded COL scaffold could effectively enhance calcium deposition and ALP activity in BM-MSCs and therefore proposed as a good candidate to accelerate the healing process of vital bone defects.
Assuntos
Células-Tronco Mesenquimais , Osteogênese , Animais , Carotenoides , Células Cultivadas , Colágeno/química , Ratos , Alicerces Teciduais/químicaRESUMO
Curcumin is extensively used in the prevention and treatment of various diseases. Recently, growing attention has been paid to the use of curcumin as a neurogenic and neuroprotective agent. This review study is aimed to collect and categorize the recent findings regarding the effects of curcumin on various neurological diseases through the induction of neural stem cell proliferation and differentiation. In addition, we have discussed the molecular mechanisms modulated by curcumin that contribute to this efficacy and have summarized the recent advancements in the novel delivery strategies used to improve the induction of neural stem cells by curcumin.
Assuntos
Curcumina/farmacologia , Doenças do Sistema Nervoso/tratamento farmacológico , Células-Tronco Neurais/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Humanos , Doenças do Sistema Nervoso/patologia , Células-Tronco Neurais/patologiaRESUMO
Nanoparticles and herbal medicines have gained considerable attention in overcoming multidrug resistance through different mechanisms. In this study, the effects of poly (Lactic-co-glycolic acid)-crocetin nanoparticles (PLGA-Crt NPs) on MRP1 and MRP2 activity in a human ovarian cisplatin-resistant carcinoma cell line (A2780-RCIS) and its parental form (A2780) were evaluated. PLGA-Crt NPs were formulated and then characterized. The cytotoxic effect of Crt, PLGA-Crt NPs, and empty PLGA NPs was assessed using MTT test in A2780 and A2780-RCIS cells. The effect of PLGA-Crt NPs on MRP1 and MRP2 mRNA expression was evaluated by Real-Time qRT-PCR. The impact of PLGA-Crt NPs on the functioning of MRP transporters was assessed by the doxorubicin efflux assay. The particle size, entrapment efficiency (EE) and loading capacity (LC) of PLGA-Crt NPs were obtained about 239.8 ± 9 nm, 79 ± 3% and 4.9 ± 0.2%, respectively. The PLGA-Crt NPs IC50 values were obtained 104 ± 3 µM and 96 ± 2 µM in A2780 and A2780-RCIS cell lines, respectively. The Real-time RT-PCR results demonstrated the inhibition of mRNA expression of MRP2 in all studied concentrations (up to 67 ± 8% at 100 µM) in A2780-RCIS cells. PLGA-Crt NPs showed more indirect efflux inhibition (up to 70 ± 5%) compared to direct inhibition (up to 49 ± 5%). The encapsulation of crocetin into PLGA NPs can increase its inhibitory effects on drug resistance by downregulating MRP2 transporters.
Assuntos
Carotenoides/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Neoplasias Ovarianas/genética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Carotenoides/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino , Relação Dose-Resposta a Droga , Regulação para Baixo , Composição de Medicamentos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteína 2 Associada à Farmacorresistência Múltipla , Neoplasias Ovarianas/tratamento farmacológico , Vitamina A/análogos & derivadosRESUMO
P-glycoprotein (P-gp) is one of the cell membrane pumps which mediate the efflux of molecules such as anticancer drugs to the extracellular matrix of tumor cells. P_gp is a member of the ATP-binding cassette (ABC) transporter family that is implicated in cancer multidrug resistance (MDR). Since MDR is a contributor to cancer chemotherapy failure, modulation of efflux pumps is a viable therapeutic strategy. In this study, new synthetic 1,4 dihydropiridine (DHP) derivatives containing thiophenyl substitution were tested as inhibitors of P-gp. Efflux assay was conducted to evaluate the intracellular accumulation of Rhodamine123 (Rh123) as a pump substrate. MTT assay, cell cycle analysis and in silico methods were also examined. Flow cytometric analysis revealed that synthetic DHP derivatives (15⯵M) increased intracellular concentration of the substrate by 2-3 folds compared with verapamil as a standard P-gp inhibitor. MTT assay on EPG85-257P and its drug-resistant EPG85-257RDB cell line revealed antitumor effects (30-45%) for new DHP derivatives at 15⯵M following 72â¯h incubation. However, MTT test on normal cell line showed negligible toxic effects. Finally combination of synthetic derivatives with doxorubicin showed that these compounds decrease IC50 of doxorubicin in resistant cell lines from 9 to 1.5⯵M. Sub-G1 peak-related apoptotic cells showed a stronger effect of synthetic compounds at 5⯵M compared with verapamil. Molecular dynamic results showed a high binding affinity between DHP derivative and protein at drug binding site. Findings of these biological tests indicated the antitumor activity and P-gp inhibitory effects of new 1,4-DHP derivatives.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Di-Hidropiridinas/química , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Antibióticos Antineoplásicos/farmacologia , Ciclo Celular , Proliferação de Células , Simulação por Computador , Humanos , Técnicas In Vitro , Neoplasias Gástricas/patologia , Células Tumorais CultivadasRESUMO
We have evaluated the capability of a collagen/poly glycolic acid (PGA) scaffold in regeneration of a calvarial bone defects in rabbits. 4 bone critical size defects (CSD) were created in the calvarial bone of each rabbit. The following 4 treatment modalities were tested (1) a collagen/PGA scaffold (0.52% w/w); (2) the collagen/PGA scaffold (0.52% w/w) seeded with adipose-derived mesenchymal stem cells (AD-MSCs, 1 × 106 cells per each defect); (3) AD-MSCs (1 × 106 cells) no scaffold material, and (4) blank control. The rabbits were then divided into 3 random groups (of 5) and the treatment outcomes were evaluated at 4, 8 and 12 weeks. New bone formation was histologically assessed. Experimental groups were analyzed by CT scan and real-time PCR. Histological analysis of bone defects treated with collagen/PGA alone exhibited significant fibrous connective tissue formation at the 12 weeks of treatments (P ≤ 0.05). There was no significant difference between collagen/PGA alone and collagen/PGA + AD-MSCs groups. The results were confirmed by CT scan data showing healing percentages of 34.20% for the collage/PGA group alone as compared to the control group and no difference with collagen/PGA containing AD-MSCs (1 × 106 cells). RT-PCR analysis also indicated no significant differences between collagen/PGA and collagen/PGA + AD-MSC groups, although both scaffold containing groups significantly express ALP and SIO rather than groups without scaffolds. Although there was no significant difference between the scaffolds containing cells with non-cellular scaffolds, our results indicated that the Collagen/PGA scaffold itself had a significant effect on wound healing as compared to the control group. Therefore, the collagen/PGA scaffold seems to be a promising candidate for research in bone regeneration.
Assuntos
Regeneração Óssea , Osso e Ossos/patologia , Colágeno/química , Ácido Poliglicólico/química , Alicerces Teciduais/química , Cicatrização , Tecido Adiposo/citologia , Animais , Materiais Biocompatíveis , Osso e Ossos/lesões , Diferenciação Celular , Linhagem da Célula , Condrócitos/citologia , Feminino , Fibroblastos/metabolismo , Consolidação da Fratura , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Coelhos , Reação em Cadeia da Polimerase em Tempo Real , Engenharia Tecidual , Tomografia Computadorizada por Raios XRESUMO
Cancers are usually treated by anticancer agents that are toxic for both normal and cancer cells, so these drugs have major side effects and they are not suitable and enough effective for cancer prevention. Solamargine, a steroidal alkaloid glycoside found in Solanum species such as Solanum nigrum, displayed several therapeutic activities. We aim to review the use of solamargine in experimental cancer studies. Articles published in biology journals between 1975 and 2017 were retrieved from PubMed, Scopus, and Web of Science using relevant keywords. The scientific papers mainly focusing on solamargine with therapeutic efficacies against cancers were identified and tabulated. In addition, the reliability of experimental findings was determined under "Risk of Bias" criteria. The author manually reviewed 33 articles; 27 articles were found concerning the anti-cancer potential in cancer cells. Solamargine has been found to possess anticancer activities via its effect on a variety of biological pathways including cell survival pathways, tumor suppressor pathways, caspase activation pathway, mitochondrial pathways, death receptor pathways, protein kinase pathways, and signal pathways, which promote invasion/migration and multi drug resistance. Solamargine can be an anticancer agent candidate when complementary scientific evidences become available. Copyright © 2017 John Wiley & Sons, Ltd.
Assuntos
Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Alcaloides de Solanáceas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Reprodutibilidade dos Testes , Transdução de Sinais/efeitos dos fármacosRESUMO
Mesenchymal stem cells (MSCs) have been designated as the most reliable cells in clinics to treat osteo-diseases because of their versatile nature. MSCs, isolated from long bone (Lb-MSCs) are rarely reported and named as RIA-MSCs because of the reamer-irrigator-aspirator (RIA) device. The potential of these cells in the treatment of non-union bone fractures made them the ideal candidates to be studied for clinical practices. In this work, effect of cryopreservation on the proliferation and differentiation capabilities of long bone MSCs (Lb-MSCs) has been studied. For this purpose, Lb-MSCs were isolated via RIA device and characterized using flow cytometry and differentiation assays. Cells were cryopreserved for 3, 6 and 12 months and thereafter were characterized using differentiation assays and genetic markers specific for osteogenic, chondrogenic, and adipogenic potential quantitatively by qRT-PCR. Lb-MSCs were found expressing MSC characteristic markers defining their identity. The population doubling time (PDT) was about 2.5 ± 0.5 days and colonies appeared after 7-10 days. Differentiation potential and gene expression of 3, 6 and 12 months cryopreserved Lb-MSCs were unaltered. The results show that cryopreservation did not have an effect on the differentiation potential of human Lb-MSCs. Therefore, our work offers Lb-MSCs as clinically cells for treating osteo-diseases.
Assuntos
Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Células-Tronco Mesenquimais/citologia , Osteogênese/fisiologia , Osso e Ossos/citologia , Técnicas de Cultura de Células/métodos , Células Cultivadas , Condrogênese/fisiologia , Criopreservação/métodos , Diástase Óssea/fisiopatologia , HumanosRESUMO
INTRODUCTION: Crocin (Cro) is a bioactive biomaterial with properties that promote osteoconduction, osteoinduction, and osteogenic differentiation, making it an ideal candidate for developing mechanically enhanced scaffolds for bone tissue engineering (BTE). Present study focused on a 3D printing matrix loaded with Cro and featuring a composite structure consisting of Chitosan (CH), collagen (Col), and hydroxyapatite (HA). METHOD: The scaffolds' structural properties were analyzed using FESEM, and FTIR DSC, while the degradation rate, swelling ratio, cell viability were examined to determine their in vitro performance. Additionally, the scaffolds' mechanical properties were calculated by examining their force, stress, elongation, and Young's modulus. RESULTS: The CH/Col/nHA scaffolds demonstrated interconnected porous structures. The cell study results indicated that the Cro-loaded in scaffolds cause to reduce the toxicity of Cro. Biocompatibility was confirmed through degradation rate, swelling ratio parameters, and contact angle measurements for all structures. The addition of Cro showed a significant impact on the strength of the fabricated scaffolds. By loading 25 and 50 µl of Cro, the Young's modulus improved by 71 % and 74 %, respectively, compared to the free drug scaffold. CONCLUSION: The obtained results indicated that the 3D printing crocin-loaded scaffolds based chitosan/collagen/hydroxyapatite structure can be introduced as a promising candidate for BTE applications.
Assuntos
Quitosana , Engenharia Tecidual , Engenharia Tecidual/métodos , Durapatita/química , Quitosana/química , Alicerces Teciduais/química , Osteogênese , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química , Colágeno , Porosidade , Impressão TridimensionalRESUMO
The ATP-binding cassette sub-family G member 2 (ABCG2) is implicated as a member of multidrug resistant proteins in tumors, mediating efflux of a wide spectrum of anticancer drugs. Pro-inflammatory cytokines, which are present within the micro-environment of tumors and inflammation, are able to modulate the expressions and activities of different drug transporters. This study was aimed to evaluate the short-term (72-h treatment) effects of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) on the expression and function of ABCG2 in cervix carcinoma and gastric cancer cells. Effects of pro-inflammatory cytokines on mRNA, protein expression, and function of ABCG2 were studied using real time RT-PCR and flow cytometry methods, respectively. HeLa cells treated with IL-1ß, IL-6, or TNF-α showed decrements in ABCG2 mRNA levels without any changes in protein expression and function of ABCG2. IL-6 and TNF-α had no effects on mRNA, protein expression, and function of ABCG2 in EPG85-257 cells. Although IL-1ß did not alter ABCG2 at mRNA or protein levels in EPG85-257 cells, it augmented function of ABCG2 in these cells. Mitoxantrone accumulation was also amplified in IL-1ß-, IL-6- or TNF-α-treated HeLa cells and in IL-1ß-treated EPG85-257 cells. In conclusion, pro-inflammatory cytokines were able to modulate the expression of ABCG2 at transcriptional and post-transcriptional levels in human cervix and gastric cancer cells.
Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Gástricas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Neoplasias do Colo do Útero/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Antineoplásicos/metabolismo , Resistencia a Medicamentos Antineoplásicos , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Mitoxantrona/metabolismo , Proteínas de Neoplasias/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Fatores de Tempo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/imunologiaRESUMO
In multidrug resistance (MDR), cancer cells exposed to anticancer agents develop resistance to a wide variety of chemicals and chemotherapeutic agents. Sesquiterpene coumarins are reported to inhibit P-glycoprotein and/or increase cytotoxicity of anticancer drugs in P-gp-overexpressing cell lines. In the current study, we investigated the effects of galbanic acid (from the roots of Ferula szowitsiana) and farnesiferol A (from the roots of Ferula persica) on functionality of the drug transporter P-glycoprotein (P-gp) using a rhodamine 123 efflux assay in a doxorubicin resistant breast cancer cell line (MCF7/Adr). Compared to verapamil, the well-known inhibitor of P-gp, galbanic acid (5, 10, and 25 µg/mL), significantly inhibited the P-gp activity. In inhibition of the P-gp transporter, farnesiferol A (0.5 µg/mL) was more potent than verapamil at 15 min exposure. Our results indicate that the plant derived sesquiterpene coumarins, farnesiferol A and galbanic acid, may be promising candidates to be considered for further studies on the reversal of multidrug resistance phenotype in chemotherapy of cancer patients.
Assuntos
Antineoplásicos/farmacologia , Cumarínicos/farmacologia , Ferula/química , Extratos Vegetais/química , Sesquiterpenos/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/efeitos dos fármacos , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos/química , Transporte Biológico , Linhagem Celular Tumoral , Cumarínicos/química , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Raízes de Plantas/química , Rodamina 123/metabolismo , Sesquiterpenos/química , Verapamil/farmacologiaRESUMO
Plants have been shown to possess a number of beneficial anticancer and immunomodulatory properties. In this study the possible in vitro antitumor activity and immunomodulatory effects of five species of Euphorbia, an important genus of Euphorbiaceae, including E. petiolata, E. hebecarpa, E. osyridea, E. microciadia, and E. heteradenia were investigated using cytotoxicity and cell proliferation assays. Among different tumor cell lines, the most sensitive cell line to methanolic extracts of the plants was determined as follows. Hela cervical cancer cells to E. hebecarpa and E. microciadia, K562 leukemia cells to E. petiolata and E. heteradenia, and Fen bladder cancer cells to E. osyridea. The methanolic extracts were then fractionated into hexane, n-butanol, ethyl acetate, and water and the effect of these fractions was tested for cytotoxic activity on the selected cell lines. The results indicated the significant stronger antiproliferatory effect of the hexane factions in all the plants when compared with other ones. The methanolic extracts of the plants were also studied for their effects on the activation of the lymphocytes. All of the extracts showed stimulatory effects on the proliferation of the lymphocytes at lower concentrations. After further fractionation of the extracts, the butanolic and hexane fractions showed the highest activity on the lymphocyte activation. In conclusion, all the plants studied had the capacity to inhibit proliferation of tumor cells with beneficial immunomodulatory effects on the lymphocytes. This dual effect of the plants indicates their value for further investigations as antitumor agents.
Assuntos
Antineoplásicos/farmacologia , Euphorbia/química , Fatores Imunológicos/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Adulto , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Fatores Imunológicos/isolamento & purificação , Ativação Linfocitária/imunologia , Linfócitos/imunologia , Masculino , Componentes Aéreos da Planta/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Especificidade da EspécieRESUMO
Severe liver diseases have been considered the most common causes of adult deaths worldwide. Until now, liver transplantation is known as the only effective treatment for end stage liver disease. However, it is associated with several problems, most importantly, the side effects of immunosuppressive drugs that should be used after transplantation, and the shortage of tissue donors compared to the increasing number of patients requiring liver transplantation. Currently, tissue/organ decellularization as a new approach in tissue engineering is becoming a valid substitute for managing these kinds of problems. Decellularization of a whole liver is an attractive procedure to create three-dimensional (3D) scaffolds that micro-architecturally and structurally are similar to the native one and could support the repair or replacement of damaged or injured tissue. In this review, the different methods used for decellularization of liver tissue have been reviewed. In addition, the current approaches to overcome the challenges in these techniques are discussed.
Assuntos
Regeneração Hepática , Fígado/patologia , Engenharia Tecidual/métodos , Alicerces Teciduais , Animais , Materiais Biocompatíveis , Matriz Extracelular , Humanos , Fígado/irrigação sanguínea , Fígado/fisiologiaRESUMO
OBJECTIVES: Mesenchymal stem cells (MSCs) extensively interact with cancer cells and other stromal cells in the tumor microenvironment. However, the role of MSCs in colorectal cancer (CRC) development and metastasis is controversial. Strong evidence demonstrated that conditioned medium (CM) obtained from MSCs regulates main cellular functions such as proliferation, differentiation, migration, and communication due to its cell secretomes. This study was designed to determine the inhibitory effect of dental pulp stem cells (DPSC) and its extracted conditioned medium (DPSC-CM) in CRC progression. MATERIALS AND METHODS: The inhibitory effects of DPSC-CM on growth, apoptosis, and migration of CRC cells were evaluated by resazurin, flow cytometry of propidium iodide (PI) stained cells, and wound closure assay, respectively. Western blotting detected the expression of MAPKinase and apoptotic proteins. Also, the homing ability of DPSCs and the invasion ability of CRC cells under indirect co-culture were assayed by the Boyden chamber assay. RESULTS: DPSC-CM reduced the viability and induced the apoptosis of CRC cells significantly. Western blot analysis confirmed the increase in cytochrome C, phospho-JNK/SAPK to JNK/SAPK ratio, cleaved-caspase 8 and 3 in treated CRC cells with DPSC-CM, and decrease in phospho-ERK (P44/42 MAPK) to ERK (P44/42 MAPK) ratio, which are involved in induction of apoptosis and growth inhibition of cancer cells with minimal change in normal cells. Also, DPSCs could migrate (homing ability) to Caco2 and SW48 cells significantly. CONCLUSION: To sum up, DPSC-CM had significant apoptotic and growth inhibitory effects on the CRC cells through the MAPKinase and apoptosis signaling pathways.
RESUMO
Chronic wounds have become a major health problem worldwide. Curcumin (Cur), with strong anti-inflammatory and anti-infective properties, is introduced as a unique molecule for wound dressing applications. In the present study, Cur-loaded chitosan/poly(ethylene oxide)/collagen (Cho/PEO/Col) nanofibers were developed for wound dressing applications by the blend-electrospinning process. Structural, mechanical, and biological properties of nanofibers were evaluated using SEM, FTIR, tensile testing, in vitro release study, Alamar blue cytotoxicity assay, and in vivo study in a rat model. According to the results, Cur was successfully released up to 3 days without any significant cytotoxicity of the above hybrid to human dermal fibroblasts. In vivo studies on full-thickness wounds in the rat model indicated significant improvement in the mean wound area closure by applying Cur-loaded Cho/PEO/Col nanofibers. The electrospun Cho/PEO/Col nanofibers loaded with Cur could be considered as a promising type of wound dressing in the wound-healing process.
Assuntos
Quitosana , Curcumina , Nanofibras , Animais , Colágeno , Curcumina/farmacologia , Ratos , CicatrizaçãoRESUMO
The aim of this study was to surface-functionalize PEGylated liposomal doxorubicin (PLD) using anti-p32 CGKRK peptide to evaluate its anti-angiogenic and anti-tumour activities. CGKRK was conjugated to DSPE-mPEG2000-maleimide and post-inserted into PLD at 25, 50, 100, 200 and 400 peptides per each liposome and characterised for their size, zeta potential, drug loading, release properties; and cell binding, cell uptake and cytotoxicity on three C26, 4T1 and human umbilical vein endothelial cell (HUVEC) cell lines. The in vitro results indicated the better efficiency of the PLD-100 (PLD with 100 CGKRK) formulation on 4T1 and HUVEC cell lines. The results of anti-tube formation and spheroid assay indicated the efficiencies of the PLD-100 formulation compared with Caelyx®in vitro. The in vivo studies indicated the higher tumour accumulation of PLD-100 formulation in comparison with Caelyx® which also implied the higher survival rates in mice treated with PLD-100 formulation. Histological evaluations demonstrated that PLD-100 had no side-effects on major organs. In conclusion, the results of this study indicated that PLD-CGKRK- could efficiently target endothelial and tumour parenchymal cells which enhance the therapeutic efficacy of PLD and merits further investigation.
Assuntos
Inibidores da Angiogênese/farmacologia , Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/análogos & derivados , Sistemas de Liberação de Medicamentos , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/química , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Maleimidas/química , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos/química , Fosfatidiletanolaminas/química , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Taxa de SobrevidaRESUMO
Electrospun hybrid nanofibers have been extensively regarded as drug carriers. This study tries to introduce a nano fibrous wound dressing as a new strategy for a topical drug-delivery system. The vancomycin (VCM)-loaded hybrid chitosan/poly ethylene oxide (CH/PEO) nanofibers were fabricated by the blend-electrospinning process. Morphological, mechanical, chemical, and biological properties of nanofibers were examined by SEM, FTIR, release profile study, tensile assay, Alamar Blue cytotoxicity evaluation, and antibacterial activity assay. In vivo wound healing activity of hybrid CH/PEO/VCM nanofibers was evaluated in full-thickness skin wounds of rats. The hybrid CH/PEO/VCM nanofibers were successfully fabricated in a nanometer. The CH/PEO/VCM 2.5% had higher Young's Modulus, better tensile strength, smaller fiber diameter with sustained-release profiles compared to CH/PEO/VCM 5%. All nanofibers did not show any significant cytotoxicity (P < 0.05) on the normal fibroblast cells. Also, VCM-load hybrid CH/PEO nanofibers successfully inhibited bacterial growth. The wound area in the rats treated with CH/PEO/VCM 2.5% was less than CH/PEO/VCM 5% treated group. According to histological evaluation, the CH/PEO/VCM 2.5% group showed the fastest wound healing than other treatment groups. Results of this study proposed that CH/PEO/VCM nanofibers could promote the wound healing process by reducing the side effects of VCM as a topical antimicrobial agent.
Assuntos
Quitosana/química , Óxido de Etileno/química , Nanofibras/química , Polietilenoglicóis/química , Vancomicina/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Bandagens , Modelos Animais de Doenças , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Vancomicina/químicaRESUMO
Breast cancer resistance protein is a member of the ATP-binding cassette transporter G family that extrudes xenotoxins from cells, mediating drug resistance, and has been recognized as a major cause of failure of various carcinoma chemotherapies. In this study, the modulatory effects of dexamethasone and indomethacin on the cell cytotoxicity of mitoxantrone and on the BCRP protein activity in breast cancer cell lines were examined. MCF cells were seeded at 1 x 10(4) cells per well in 96-well flat-bottomed microplates for 48 hours and treated with increasing doses of dexamethasone, indomethacin, and novobiocin alone or preincubated with increasing doses of the drugs and then coexposed to mitoxantrone. Cell viability was measured after 1-4 days, using the MTT assay. BCRP activity was determined flow cytometrically by measuring mitoxantrone accumulation in the absence and presence of the inhibitor, novobiocin. Cotreatment of mitoxantrone with different concentrations of dexamethasone and indomethacin sensitized parental and resistant MCF-7 cells to mitoxantrone cytotoxicity. Dexamethasone increased the accumulation of mitoxantrone in the MCF-7/MX cell line, indicating an inhibition of BCRP. In spite of increased levels of mitoxantrone cytotoxicity in the presence of indomethacin, the accumulation of mitoxantrone was not increased in indomethacin-treated MCF cells.