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An imbalance between caloric intake and energy expenditure leads to obesity. Obesity is an important risk factor for the development of several metabolic diseases including insulin resistance, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. So, controlling obesity could be effective in the improvement of obesity-related diseases. Various factors are involved in obesity, such as AMP-activated protein kinases (AMPK), silent information regulators, inflammatory mediators, oxidative stress parameters, gastrointestinal hormones, adipokines, angiopoietin-like proteins, and microRNAs. These factors play an important role in obesity by controlling fat metabolism, energy homeostasis, food intake, and insulin sensitivity. AMPK is a heterotrimeric serine/threonine protein kinase known as a fuel-sensing enzyme. The central role of AMPK in obesity makes it an attractive molecule to target obesity and related metabolic diseases. In this review, the critical role of AMPK in obesity and the interplay between AMPK and obesity-associated factors were elaborated.
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Proteínas Quinasas Activadas por AMP , Resistencia a la Insulina , Obesidad , Humanos , Proteínas Quinasas Activadas por AMP/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo Energético/fisiología , Resistencia a la Insulina/fisiología , Enfermedades Metabólicas , Obesidad/complicaciones , Obesidad/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismoRESUMEN
BACKGROUND: Despite many efforts to discover the important role of the autophagy process in the pathogenesis of colorectal cancer (CRC), the exact involved molecular mechanism still remains to be elucidated. Recently, a limited number of studies have been employed to discover the impact of autophagy genes' variants on the development and progression of CRC. Here, we evaluated the association between two single-nucleotide polymorphisms (SNPs) in the main components of the autophagy genes, ATG16L1 rs2241880, and ATG5 rs1475270, and the CRC risk in an Iranian population. METHODS: During this investigation, a total of 369 subjects, including 179 CRC patients and 190 non-cancer controls have been genotyped using Tetra-primer amplification refractory mutation system-polymerase chain reaction (TP-ARMS-PCR) method. RESULT: The results demonstrated that the T allele of the ATG16L1 rs2241880 was significantly associated with the increased risk of CRC in the studied population (OR 1.64, 95% CI: 1.21-2.22, p = 0.0015). Moreover, ATG16L1 rs2241880 TT genotype increased the susceptibility to CRC (OR 3.31, 95% CI: 1.64-6.69, p = 0.0008). Furthermore, a significant association was observed under the recessive and dominant inheritance models (p = 0.0015 and p = 0.017, respectively). No statistically significant differences were found in the ATG5 rs1475270 alleles and genotypes between the cases and controls. CONCLUSION: The results of the present study may be helpful concerning the risk stratification in CRC patients based on the genotyping approach of autophagy pathways and emphasize the need for further investigations among different populations and ethnicities to refine our conclusions.
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Proteínas Relacionadas con la Autofagia/genética , Neoplasias Colorrectales , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Autofagia/genética , Estudios de Casos y Controles , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Humanos , Masculino , Persona de Mediana EdadRESUMEN
This study was aimed to evaluate the protective effects of Chlorella Vulgaris (CVE) (50 and 100 mg/kg doses) on sperm DNA fragmentation, testis oxidative stress in Carbon tetrachloride (CCL4)-exposed rats. Thirty healthy male Wistar rats were divided into five groups (n = 6): Control; CCl4; CVE; CCl4 + CVE50; CCl4 + CVE100. At the end of the experiment, the testicular oxidative stress parameters were estimated. The Chromomycin A3 (CMA3) and Acridine orange (AO) staining were performed to examine the sperm DNA fragmentation status. CCl4 treatment showed a significant decrease in antioxidant markers and sperm count, viability, normal morphology and motility as well as significantly increased the testicular oxidative stress markers, and the percentage of CMA3 and AO positive sperms in normal rats (p < 0.05). While CVE supplementation has revealed a significant decrease in the percentage of CMA3 and AO positive sperms as well as testicular oxidative stress markers and considerably improved the testis antioxidant status (p < 0.05). CVE has also increased the number of sperms with forwarding movement, normal morphology and viability (p < 0.05). Taken together, our analyses suggest that CVE may play a critical role in attenuating the CCl4-induced oxidative stress in the testis, thereby protecting the sperm membrane and DNA against oxidative damage.
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Chlorella vulgaris , Testículo , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Tetracloruro de Carbono/toxicidad , Chlorella vulgaris/metabolismo , Masculino , Estrés Oxidativo , Ratas , Ratas Wistar , SemillasRESUMEN
This study was conducted to present the mechanism of the therapeutic effects of Chlorella vulgaris extract (CV) on the carbon tetrachloride (CCl4) induced liver fibrosis model. Primarily, the mechanism of antioxidant effects of CV were investigated via measuring the expression of forkhead box protein O1 (FOXO1) and phosphorylated 5' adenosine monophosphate-activated protein kinase (p-AMPK) as upstream regulators of superoxide dismutase (SOD) and catalase (CAT). Subsequently, we investigated the regulatory effect of CV treatment on the yes-associated protein (YAP) and transcriptional coactivators with a PDZ-binding motif (TAZ) as fibrogenic factors. Male Wistar rats received CCl4 and olive oil solution 1 ml/kg intraperitoneally for 12 weeks, twice weekly. CV 50 and 100 mg/kg were administered on a daily basis by gavage in the last 4 weeks. Ultimately, liver marker enzymes and hepatic hydroxyproline content were measured. The activity of SOD and CAT and the expression of YAP, TAZ, FOXO1, SOD, and CAT were analyzed. Finally, the protein levels of YAP, TAZ, and p-AMPK were detected. CV administration decreased liver marker enzymes and hydroxyproline content significantly. The expression and protein levels of YAP and TAZ reduced by CV treatment. Furthermore, the augmentation of expression and function of CAT and SOD by CV treatment was followed by an increase in the expression of FOXO1 and protein level of p-AMPK. Our data revealed that the stimulation of expression and function of SOD and CAT by CV treatment could be mediated by FOXO1/p-AMPK axis. Moreover, anti-fibrotic effect of CV might be associated with its inhibitory effect on the hepatic expression of YAP and TAZ. Chlorella vulgaris treatment ameliorates liver fibrosis via two cellular mechanisms. A) Likely, Chlorella vulgaris treatment increases gene expression of enzymatic antioxidants superoxide dismutase (SOD) and catalase (CAT) via upregulating its upstream regulatory elements i.e. phosphorylated 5' adenosine monophosphate-activated protein kinase (p-AMPK) and forkhead box protein O1 (FOXO1). These possible regulatory effects maybe lead to reduce reactive oxygen species level (ROS). B) Chlorella vulgaris treatment decreases hepatic protein level and gene expression of key elements of Hippo signaling pathway i.e. Yes-associated protein (YAP) and Transcriptional coactivators with a PDZ-binding motif (TAZ). Figure created with BioRender ( https://biorender.com ). ROS: Reactive oxygen species, YAP: Yes-associated protein, TAZ: Transcriptional coactivators with a PDZ-binding motif, FOXO1: Fork head Box O1, AMPK: 5' adenosine monophosphate activated protein kinase, SOD: Superoxide dismutase, CAT: Catalase, P: Phosphate group.
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Chlorella vulgaris/química , Péptidos y Proteínas de Señalización Intracelular/genética , Cirrosis Hepática/tratamiento farmacológico , Proteínas del Tejido Nervioso/genética , Animales , Antioxidantes/química , Antioxidantes/farmacología , Tetracloruro de Carbono/toxicidad , Catalasa/genética , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/genética , Cirrosis Hepática/patología , Ratas , Transducción de Señal/efectos de los fármacos , Superóxido Dismutasa-1/genética , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ , Proteínas Señalizadoras YAPRESUMEN
BACKGROUND: The cytochromes P450 are a superfamily of enzymes that control the synthesis of the biologically active form of vitamin D, 1,25-dihydroxyvitamin D3. These enzymes contribute to the formation of 1,25-dihydroxyvitamin D3, which starts with a 25-hydroxylation by CYP2R1 and CYP27A1 and a subsequent 1α-hydroxylation via CYP27B1. METHODS: By using quantitative real-time polymerase chain reaction (qRT-PCR), we analyzed the expression ratio of CYP2R1, CYP27A1 and CYP27B1 genes within the vitamin D metabolic pathway in a total of 75 colorectal cancer (CRC) tissues compared to the adjacent tissues. Furthermore, we evaluated the association of CYP27B1 rs4646536 and CYP2R1 rs12794714 and rs10766196 polymorphisms with CRC risk in a total of 490 subjects, including 245 CRC patients and 245 non-cancer controls. The genotyping was performed using tetra-primer amplification refractory mutation system polymerase chain reaction (TP-ARMS-PCR) method. RESULTS: The results indicated 2.3 and 2.7 upregulation of CYP2R1 and CYP27B1 genes in colorectal cancer tissues compared to the adjacent tissues, respectively. Rs12794714 AG genotype increased the risk of CRC (P = .03). Furthermore, a significant association was observed under the dominant inheritance model (P = .039). CONCLUSION: CYP2R1 and CYP27B1 genes were over-expressed in CRC samples compared to the adjacent control tissues. Furthermore, CYP2R1 rs12794714 variant was associated with the risk of CRC in the studied samples. CYP2R1 rs10766196 and CYP27B1 rs4646536 are not responsible for CYP2R1 and CYP27B1 genes expression alteration, respectively, but CYP2R1 rs12794714 polymorphism may be the reason of CYP2R1 upregulation and increased the risk of CRC.
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25-Hidroxivitamina D3 1-alfa-Hidroxilasa/genética , Colestanotriol 26-Monooxigenasa/genética , Neoplasias Colorrectales/genética , Familia 2 del Citocromo P450/genética , Anciano , Estudios de Casos y Controles , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Frecuencia de los Genes , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Vitamina D/biosíntesis , Vitamina D/genéticaRESUMEN
In the current study, we aimed to investigate the effect of carvacrol on the suppression of liver fibrosis progression through targeting lysyl oxidase (LOX) expression. The rats received carbon tetrachloride (CCl4) intraperitoneally and carvacrol orally for 10 weeks. Liver damage was evaluated by measuring the serum level of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase and hepatic oxidative stress parameters including total antioxidant capacity, total thiol group and total oxidant status spectrophotometry and malondialdehyde fluorometrically. Extracellular deposition of collagen was detected using Masson's trichrome standing. Furthermore the gene expression of lysyl oxidase homolog 2 (Loxl2) was analyzed using quantitative reverse transcription-polymerase chain reaction. And then the protein level of LOX was detected in liver tissue by western blot method. Carvacrol administration normalized serum biochemical parameters and improved oxidative stress status in liver homogenate of CCl4 treated rats. Collagen fiber bundles in interlobular spaces were decreased remarkably by carvacrol treatment. Also, carvacrol downregulated hepatic gene expression of Loxl2 and protein level of LOX. Our data clearly revealed that carvacrol suppresses progression of liver fibrosis development via attenuating of liver damage and oxidative stress status as well as via downregulation of hepatic gene expression of Loxl2 and protein level of LOX.
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Inhibition of inflammation is one of the possible therapeutic approaches for Insulin resistance (IR) during type 2 diabetes mellitus (T2DM). In the current study we investigated the effects of palmitate and chicoric acid (CA) on inflammation in peripheral blood mononuclear cells (PBMCs) of newly diagnosed T2DM patients and healthy subjects and explored the mechanism by which palmitate and CA influence inflammation. 20 newly diagnosed T2DM patients and 20 healthy subjects were recruited in our study. Blood sample were collected and PBMCs were isolated. Interleukin 6 (IL6), silent information regulator type 1 (SIRT1), AMP-activated protein kinase (AMPK) and phospho-AMPK (pAMPK) were evaluated both in vivo and in vitro. PBMCs were treated with palmitate and CA to investigate their effects on inflammation. IL6 and SIRT1 genes expression were evaluated by real-time PCR. The levels of IL6 in culture medium were measured by ELISA. Proteins levels of AMPK and pAMPK in PBMCs were detected by western blotting. IL6 expression was higher and SIRT1 expression and pAMPK levels were lower in PBMCs of diabetic patients and obese subjects compared to healthy subjects and non-obese subjects, respectively. CA significantly prevented against increased IL6 levels as well as its gene expression in PBMCs induced by palmitate. Also, CA returned reduction in SIRT1 expression and pAMPK levels mediated via palmitate to near control level. These findings reveal that CA reduces inflammation in PBMCs probably through upregulation of SIRT1 and pAMPK. Therefore, CA would be suggested as a novel agent for the treatment of T2DM.
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Antiinflamatorios/farmacología , Ácidos Cafeicos/farmacología , Diabetes Mellitus Tipo 2/inmunología , Neutrófilos/inmunología , Palmitatos/farmacología , Succinatos/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Adulto , Diabetes Mellitus Tipo 2/patología , Femenino , Humanos , Inflamación/prevención & control , Resistencia a la Insulina/fisiología , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Sirtuina 1/metabolismoRESUMEN
Objective: Little is known about the exact underlying molecular mechanisms of the hepatoprotective effect of carvacrol against liver fibrosis. In the current study, we aimed to investigate the effect of carvacrol on the suppression of liver fibrosis progression via regulation of yes-associated protein (YAP) and transcriptional coactivators with a PDZ-binding motif (TAZ) and transforming growth factor beta (TGF-ß) pathway. Materials and methods: To fulfill our target, rats received carbon tetrachloride (CCl4) and carvacrol intraperitoneally, and orally, respectively for 10 weeks. Body weight, liver weight, serum biochemical parameters, hepatic hydroxyproline content, and histological changes were determined. Furthermore, gene expression of collagen and key elements of Hippo and TGF-ß pathways were analyzed and then the protein levels of YAP, TAZ, and TGF-ß were detected in liver tissue. Results: Carvacrol administration normalized liver and body weight, serum biochemical parameters and hepatic hydroxyproline in CCl4 treated rats. Also, carvacrol downregulated TAZ and TGF-ß signaling pathway at transcriptional levels. Furthermore, carvacrol decreased hepatic protein levels of TGF-ß, TAZ, and YAP. Low expression of TAZ and YAP were accompanied with inhibition of TGF-ß signaling pathway. Conclusion: Our data clearly revealed that carvacrol suppresses the progression of liver fibrosis via targeting of TAZ, YAP, and TGF-ß signaling pathway.
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Antiinflamatorios/farmacología , Proteínas Reguladoras de la Apoptosis/metabolismo , Cirrosis Hepática Experimental/prevención & control , Monoterpenos/farmacología , Factores de Transcripción/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Aciltransferasas , Animales , Tetracloruro de Carbono , Cimenos , Progresión de la Enfermedad , Hígado/efectos de los fármacos , Hígado/inmunología , Hígado/metabolismo , Cirrosis Hepática Experimental/inmunología , Cirrosis Hepática Experimental/metabolismo , Masculino , Ratas Wistar , Transducción de Señal , Proteínas Señalizadoras YAPRESUMEN
Objectives: In the current study, we aimed to investigate the effect of administration of resveratrol (RES) and beta-aminopropionitrile (BAPN) separately and together on the liver fibrosis progression via regulation of the gene expression and protein level of lysyl oxidase (LOX).Materials and methods: The six-week old Wistar rats received carbon tetrachloride (CCl4) intraperitoneally and RES and BAPN were administrated orally for eight weeks. The hepatoprotective effects of RES, BAPN, and combination treatment were evaluated. Then the hepatic protein and gene expression levels of LOX were measured.Results: Both RES and BAPN showed the antifibrotic effect through the reduction of collagen fiber bundles, hepatic hydroxyproline content, and protein level of LOX. The antifibrotic effect increased when RES and BAPN up-taken together.Conclusion: The co-administration of RES and BAPN can be considered as a promising therapeutic approach via targeting LOX.
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Aminopropionitrilo/farmacología , Intoxicación por Tetracloruro de Carbono/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Cirrosis Hepática/tratamiento farmacológico , Proteína-Lisina 6-Oxidasa/inmunología , Resveratrol/farmacología , Animales , Intoxicación por Tetracloruro de Carbono/inmunología , Intoxicación por Tetracloruro de Carbono/patología , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/inmunología , Cirrosis Hepática/patología , Masculino , Ratas , Ratas WistarRESUMEN
Matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) have an important role in the reproductive system and in the fertilisation process. The aim of this study was to investigate the MMP2 and MMP9 activity in semen and their association with the pregnancy rate, semen parameters and seminal plasma oxidative stress parameters in couples who were treated with intrauterine insemination (IUI). The semen specimens were obtained from 60 men who attended with their spouse for the IUI in the infertility unit. A controlled ovarian stimulation was performed with clomiphene citrate in IUI cycles. Women with positive pregnancies were recorded (n = 29). The results showed the activity of sperm MMP2 and seminal plasma MMP9 was significantly higher in the pregnant group, compared to the non-pregnant group (p < .05). There was a correlation between the sperm MMP2 activity and the total thiol group (TTG) (r = 0.276, p < .05) and the total antioxidant capacity (TAC) of seminal plasma (r = 0.304, p < .05). The sperm MMP9 showed a positive correlation with the seminal plasma TAC (r = 0.330, p < .05) and an inverse correlation with the lipid peroxidation (LP) of seminal plasma (r = -304, p< 0.05). In addition, the seminal plasma MMP2 activity was correlated to sperm viability (r = 0.266, p< .05) and the TTG of seminal plasma (r = 0.298, p < .05). The MMP2 activity in the sperm may be an important factor for determining the pregnancy rate after IUI. Impact statement What is already known on this subject? Previous studies have reported that the fusion between the sperm and zona pellucida required the activity of matrix metalloproteinase 2 (MMP2), whereas the inhibition of MMP2 can significantly decrease the in vitro fertilisation (IVF) rate. What do the results of this study add? This study has identified that the sperm MMP2 activity was significantly higher in the pregnant couples in comparison with the non-pregnant couples, who treated with intrauterine insemination (IUI). The findings showed there was a correlation between sperm MMP2 activity and the total thiol group (TTG) and the total antioxidant capacity (TAC) of the seminal plasma. What are the implications of these findings for clinical practice and/or further research? MMP2 activity in the sperm could influence the IUI outcome and it is an important factor for IUI success.
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Inseminación Artificial Homóloga , Metaloproteinasa 2 de la Matriz/metabolismo , Espermatozoides/enzimología , Adulto , Antioxidantes/análisis , Estudios de Casos y Controles , Clomifeno/administración & dosificación , Femenino , Humanos , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Inducción de la Ovulación/métodos , Embarazo , Estudios Prospectivos , Semen/química , Semen/enzimología , Espermatozoides/fisiología , Compuestos de Sulfhidrilo/análisisRESUMEN
Objective: Sphingosine 1-phosphate (S1P) signaling pathway is involved in the pathogenesis of type 2 diabetes (T2D). So, targeting S1P signaling pathway could be considered as potential therapeutic target for T2D. The aim of this study was to investigate the effects of palmitate and chicoric acid (CA) on S1P signaling pathway in peripheral blood mononuclear cells (PBMCs) from newly diagnosed patients with T2D. Materials and methods: 20 newly diagnosed patients with T2D, aged 40-60 years, were enrolled in the study. PBMCs were isolated and then treated as follows: control groups (untreated, treated with BSA 1% for 12 h), CA groups (treated with 50 µM CA for 6 h), palmitate groups (treated with 500 µM palmitate for 12 h), palmitate + CA groups (treated with 500 µM palmitate for 12 h and then treated with 50 µM CA for 6 h). Finally, sphingosine kinase 1 (SPHK1) and sphingosine 1-phosphate receptor 1 (S1PR1) genes expression were evaluated by real-time PCR and S1PR1 protein levels were quantified using ELISA. Results: Palmitate significantly increased SPHK1 and S1PR1 genes expression and S1PR1 protein levels in PBMCs of patients with diabetes. However, CA ameliorates palmitate-increased SPHK1 and S1PR1 genes expression and S1PR1 levels in these cells. Conclusion: These data indicate that CA could be considered as a novel S1P signaling pathway inhibitor through down regulation of SPHK1 and S1PR1.
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Targeting irisin as a myokine/adipokine is a new therapeutic approach in the improvement of insulin-resistance (IR) during type 2 diabetes (T2D). In present study we evaluated the effects of palmitate and chicoric acid (CA) on irisin production in peripheral blood mononuclear cells (PBMCs) of patients with T2D. This study performed on 20 newly diagnosed patients with T2D and 20 healthy subjects. PBMCs treated with palmitate and CA. PPARGC1A and FNDC5 genes expression assessed using qRT-PCR. Irisin levels in cell culture medium measured by ELISA. Palmitate decreased PPARGC1A and FNDC5 genes expression, as well as irisin levels in PBMCs from T2D and healthy volunteers. CA significantly restored palmitate-induced decrease in PPARGC1A gene expression in PBMCs of healthy subjects. Although, FNDC5 gene expression and irisin levels were not induced significantly by CA. In conclusion, palmitate decreases irisin production through down-regulation of PPARGC1A and FNDC5 expressions. However, CA does not effect on irisin pathway.Key pointsPalmitate reduced PPARGC1A and FNDC5 genes expression, as well as irisin secretion in PBMCs.Palmitate-induced decrease in PPARGC1A gene expression significantly has been reversed by CA in PBMCs of healthy subjects.CA did not return palmitate-decreased in FNDC5 gene expression and irisin levels in PBMCs.
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Diabetes Mellitus Tipo 2 , Ácidos Cafeicos , Fibronectinas/genética , Voluntarios Sanos , Humanos , Leucocitos Mononucleares/metabolismo , Palmitatos/farmacología , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , SuccinatosRESUMEN
Breast cancer is one of the most prevalent and deadliest cancers among women in the world because of its aggressive behaviour and inadequate response to conventional therapies. Cellular and gene therapies based on mesenchymal stem cells (MSCs) represent promising treatment strategies for multiple diseases, such as cancers. MSCs are multipotent adult stem cells with important features for cell therapy, such as tissue homing to injured sites, their differentiation potential, their capacity of secreting plenty of trophic factors, and low immunogenicity. The quite easy isolation of these cells from various types of tissues are associated with no ethical concern when dealing with foetal or embryonic stem cells. The MSCs exhibit both pro and anti-oncogenic properties. However, genetic engineering of MSCs and nanoparticles is being employed as a means to solve some of these problems and improve the antitumor properties of these cells. The tumour-homing ability of MSCs and their exosomes to tumour niches have made them as a promising vector for targeted delivery of therapeutic agents to tumours site. The present study investigated MSCs specifications, pro- and anti-oncogenic properties of MSCs in breast cancer, and reviewed targeted breast cancer therapy via engineered MSCs, likely as potent cellular vehicles.
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Bioingeniería/métodos , Neoplasias de la Mama/terapia , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Células Madre Mesenquimatosas/citología , Animales , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos/métodos , Exosomas/metabolismo , Femenino , Humanos , Receptores Toll-Like/metabolismoRESUMEN
Background: The present study aimed to evaluate the effects of different concentrations of cerium oxide nanoparticles (CONPs) on the oxidative stress (OS) status in kidney, lung, and serum of rats. Methods: Male Wistar Rats were treated intraperitoneally with 15, 30, and 60 mg/kg/day of CONPs. The biochemical parameters, including total antioxidant capacity (TAC), total thiol group (TTG), malondialdehyde (MDA), SOD (superoxide dismutase), and catalase (CAT) were assayed in serum, kidney, and lung tissues. Results: MDA decreased, but TTG and CAT increased in serum by the administration of CONPs at 15 mg/kg. In kidney homogenate obtained from the group treated with CONPs at 15 mg/kg, TAC, TTG, and CAT significantly increased compared to the control group. However, CONPs at 15, 30, and 60 mg/kg significantly decreased MDA level compared to the control group. In lung tissue, CONPs in doses of 15, 30 and 60 mg/kg significantly decreased CAT activity, TTG and TAC compared to the control group, while in kidney tissue, CONPs at the concentrations of 30 and 60 mg/kg significantly increased MDA compared to the control group. Conclusion: Our findings suggest that CONPs attenuate OS in the kidney and affect the serum levels of OS-related markers but induce OS in the lung tissue in a dose-dependent manner.
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Biomarcadores/sangre , Cerio/toxicidad , Riñón/patología , Pulmón/patología , Nanopartículas/toxicidad , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Catalasa/sangre , Catalasa/metabolismo , Riñón/enzimología , Pulmón/enzimología , Masculino , Ratas Wistar , Superóxido Dismutasa/sangre , Superóxido Dismutasa/metabolismoRESUMEN
In the current study, we developed resveratrol (RES)-loaded solid lipid nanoparticle (SLN-RES) in order to improve insulin resistance through the upregulation of SNARE protein complex in rats with type 2 diabetes. The SLN-RES characteristics include the following: the average size of 248 nm, the zeta potential of - 16.5 mV, and 79.9% RES entrapment efficiency. The release profile of SLN-RES showed an initial burst followed by a sustained release in natural condition. Infrared spectroscopy results revealed good incorporation of RES into core SLN. Spherical nanoparticle with less aggregation was observed under electronic microscopic examination. Oral administration of SLN-RES prevented weight loss and showed better hypoglycemic effect than RES. Serum oxidative stress status was restored to the normal level by SLN-RES. Furthermore, expression of synaptosomal-associated protein 23 (Snap23), syntaxin-4 (Stx4), and vesicle-associated membrane protein 2 (Vamp2) as the major elements of SNARE protein complex were reduced by SLN-RES more significantly than RES treatment in muscle tissue. However, SLN-RES has a similar effect to RES treatment in adipose tissue. Taken together, our results revealed SLN-RES could be a modern and interestingly therapeutic approach for the improvement of insulin resistance through targeting the expression of Snap23, Stx4, and Vamp2 in adipose and muscle tissues.
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OBJECTIVE: Oxidative stress and inflammation play an important role in the pathogenesis of diabetes and its complication. In this study, we aimed to evaluate and compare oxidative stress markers and antioxidant enzymes activity, as well as Interleukin 6 (IL-6) level in newly diagnosed type 2 diabetes mellitus (T2DM) patients and healthy subjects. MATERIAL AND METHODS: 30 newly diagnosed type 2 diabetes patients and 30 healthy subjects (age and sex matched) were recruited in this study. After anthropometric parameters measurement, blood sample were collected from all participant. Serum and plasma were isolated. Biochemical parameters were evaluated in serum. Plasma was used to measure malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC) levels, as well as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity. Also, IL-6 level was investigated in plasma using ELISA method. RESULTS: MDA and TOS levels were significantly higher in T2DM patients than the control group (p < 0.05). However, TAC and SOD were significantly lower in T2DM as compared with healthy subjects (p < 0.05). Also, IL-6 level was higher in T2DM in comparison to healthy subjects (p = 0.004). Furthermore, there was a significant positive correlation between IL-6 with MDA (p = 0.031, r = 0.482) and TOS (p < 0.001, r = 0.744). In addition, a negative correlation was observed between IL-6 and SOD activity (p = 0.002, r = -0.660). CONCLUSION: Reducing oxidative stress and inflammation could be effective in improvement of T2DM.
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Background Obesity is associated with oxidative stress. Superoxide dismutase (SOD) is the first line of defense against reactive oxygen species (ROS), eliminating the strong superoxide radical and producing H2O2, which can then be degraded by catalase (CAT). The main objective of this study was to evaluate the gene expression antioxidant enzymes (Mn-SOD and CAT) in peripheral blood mononuclear cells (PBMCs) of obese and normal-weight children, and its association with anthropometric and biochemical parameters. Methods Thirty obese and 30 control subjects between the ages of 8 and 16 years were enrolled in this study. Serum insulin levels were measured using enzyme-linked immunosorbent assay (ELISA), and insulin resistance was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). Biochemical parameters were also measured. PBMCs of the subjects were separated and Mn-SOD and CAT gene expression was measured using real-time polymerase chain reaction (PCR). Results Mn-SOD and CAT gene expression was significantly lower in the obese group compared with the control group (p<0.01). Also, a positive correlation was observed between the gene expression of Mn-SOD and CAT and body mass index (BMI), fasting blood sugar, insulin resistance, low density lipoprotein-cholesterol (LDL-C) cholesterol, triglycerides (TG) and systolic blood pressure (SBP). Conclusions Induction of antioxidants, especially Mn-SOD and CAT, can lead to reduction of oxidative stress and prevent the complications of obesity in children.