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Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease with a global prevalence, and modulation of ANGPTL8 expression has emerged as a promising predictor of NAFLD susceptibility. This research was conducted to scrutinize ANGPTL8 protein expression in NAFLD patients and elucidate the interplay between ANGPTL8 gene polymorphisms and their lipid profiles, thus shedding new light on the pathophysiology of this complex disease. The study comprised 423 unrelated participants, including 222 healthy controls and 201 individuals with NAFLD, screened using FibroScan/ultrasonography and laboratory tests. The main goal focused on the genotype and allele frequency distribution in the ANGPTL8 gene, specifically analyzing two genetic variations: rs737337 (T/C) and rs2278426 (C/T). The participants diagnosed with NAFLD were slightly younger (P ≥ 0.05) and had a higher body mass index (BMI) than the individuals in the control group. Notably, there was a significant difference in the occurrence of the rs737337 polymorphism between the NAFLD and control groups, with a lower frequency observed in the NAFLD group. Our results indicated that individuals with the TC + CC genotype and C allele of rs737337 (T/C) had a decreased risk of higher levels of ALT and AST. Conversely, those with the CT, CT + TT genotype, and T allele of rs2278426 (C/T) exhibited an increased risk of higher levels of ALT and AST. The results imply that the rs2278426 (C/T) variant of the ANGPTL8 gene is more strongly linked to an increased risk of NAFLD compared to the rs737337 polymorphism. However, additional research is needed to understand the specific molecular mechanisms responsible for the upregulation of ANGPTL8 in individuals with NAFLD.
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Enfermedad del Hígado Graso no Alcohólico , Hormonas Peptídicas , Humanos , Adulto , Predisposición Genética a la Enfermedad , Enfermedad del Hígado Graso no Alcohólico/genética , Irán , Genotipo , Alelos , Proteína 8 Similar a la Angiopoyetina , Hormonas Peptídicas/genéticaRESUMEN
Oxidative stress plays an important role in the pathology of thyroid disorders. This study examined the effect of gallic acid (GA) on the oxidative status and expression of liver antioxidant genes including thioredoxin (TXN1 & TXN2) and thioredoxin reductase1 (TXNRd1) in hypo- and hyperthyroid rat models. Forty-nine male Wistar rats were randomly assigned into seven groups as follows: control group, hypothyroid and hyperthyroid groups respectively induced by propylthiouracil and levothyroxine, hypo- and hyper thyroid-treated groups (where the groups were separately treated with 50 and 100 mg/kg of GA daily, orally). The levels of thyroid hormones and serum oxidative stress markers were evaluated after 5 weeks. The relative expression of TXN1,2 and TXNRd1 genes was measured via real-time qRT-PCR. The mean level of total antioxidant capacity (TAC), malondialdehyde, and uric acid index diminished in the hypothyroid group. Increased TAC reached almost the level of control in hypothyroid groups treated with GA. Elevation of thiol index in the hypothyroid group was observed (p < 0.01), which diminished to the control level after GA treatment. The relative expression of TXN1, TXNRd1, and TXN2 genes in the hypothyroid and hyperthyroid groups significantly increased compared to the control group (p ≥ 0.05), but in the groups treated with GA, the expression of these genes declined significantly (p ≥ 0.05). Our results indicated GA can affect the expression of TXN system genes in the rat liver. Also, the results suggest GA has a more positive effect on modulating serum oxidative parameters in hypothyroid rat models than in hyperthyroid.
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Hipertiroidismo , Hipotiroidismo , Ratas , Masculino , Animales , Tiorredoxina Reductasa 1/genética , Tiorredoxina Reductasa 1/metabolismo , Antioxidantes/metabolismo , Ácido Gálico/farmacología , Ratas Wistar , Hipertiroidismo/inducido químicamente , Hipertiroidismo/tratamiento farmacológico , Hipertiroidismo/genética , Hipotiroidismo/inducido químicamente , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/genética , Estrés Oxidativo , Factores Inmunológicos , Tiorredoxinas/genética , Tiorredoxinas/toxicidad , Tiorredoxinas/metabolismoRESUMEN
Metastatic breast cancer remains a serious health concern and numerous investigations recommended medicinal plants as a complementary therapy. Crocin is one of the known anticancer bio-component. Recently, the inhibitory effect of metformin has been studied on the various aspects of cancer. However, no study reported their combination effects on metastatic breast cancer. In the present study, we have assessed their anti-metastatic effects on in vitro and in vivo breast cancer models. Using MTT assay, scratch, and adhesion tests, we have evaluated the cytotoxic, anti-invasive and anti-adhesion effects of crocin and metformin on 4T1 cell line, respectively. Their protective effects and MMP9 as well as VEGF protein expression levels (Western blotting) investigated in the 4T1 murine breast cancer model. Our results showed that both crocin and metformin reduced cell viability, delayed scratch healing and inhibited the cell adhesion, in vitro. While crocin alone restored the mice's weight reduction, crocin, metformin, and their combination significantly reduced the tumor volume size and enhanced animal survival rate in murine breast cancer model, responses that were associated with VEGF and MMP9 down-regulation. These findings suggest that a combination of crocin and metformin could serve as a novel therapeutic approach to enhance the effectiveness of metastatic breast cancer therapy.
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Neoplasias de la Mama/tratamiento farmacológico , Carotenoides/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Metaloproteinasa 9 de la Matriz/química , Metformina/farmacología , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Animales , Apoptosis , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular , Progresión de la Enfermedad , Quimioterapia Combinada , Femenino , Humanos , Hipoglucemiantes/farmacología , Técnicas In Vitro , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Ulcerative colitis (UC) and Crohn's disease (CD) are two major forms of inflammatory bowel disease (IBD), which is an inflammatory disease. Studies have shown that adipose tissue and inflammation play important roles in the pathogenesis of IBD. C1q/TNF-related protein-3 (CTRP3) is a newly discovered adipokine playing a substantial role during inflammatory process, and for the first time in the present study, serum levels of this adipokine were measured in the UC and CD patients. This case-control study included 70 control, 50 UC, and 50 CD patients who were diagnosed by standard criteria. Serum levels of adiponectin, IL-6, TNF-α, TGF-ß, and CTRP3 were evaluated using ELISA kits. Serum levels of IL-6, TNF-α, and TGF-ß elevated in the UC and CD patients compared with the controls while adiponectin and CTRP3 diminished in the patient's groups compared with the control. Furthermore, decrease in CTRP3 serum levels was associated with the risk of UC and CD diseases. Moreover, CTRP3 indicated negative correlation with BMI, FBS, insulin, homeostasis model assessment of insulin resistance, IL-6, TNF-α, and TGF-ß and also a positive correlation with adiponectin in both the UC and CD patients. For the first time, the present study demonstrated lower levels of CTRP3 in the UC and CD patients. Decreased serum levels of CTRP3 and its inverse relationship with inflammatory cytokines and TGF-ß levels suggested a possible role for CTRP3 in the pathogenesis of UC and CD diseases.
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Colitis Ulcerosa/sangre , Enfermedad de Crohn/sangre , Enfermedades Inflamatorias del Intestino/sangre , Resistencia a la Insulina/genética , Factores de Necrosis Tumoral/sangre , Adipoquinas/sangre , Adiponectina/sangre , Adulto , Colitis Ulcerosa/genética , Colitis Ulcerosa/patología , Enfermedad de Crohn/genética , Enfermedad de Crohn/patología , Citocinas/sangre , Citocinas/genética , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/patología , Insulina/sangre , Interleucina-6/sangre , Masculino , Factor de Crecimiento Transformador beta/sangre , Factor de Necrosis Tumoral alfa/sangre , Factores de Necrosis Tumoral/genéticaRESUMEN
BACKGROUND: Melanoma as a type of skin cancer, is associated with a high mortality rate. Therefore, early diagnosis and efficient surgical treatment of this disease is very important. Photodynamic therapy (PDT) involves the activation of a photosensitizer by light at specific wavelength that interacts with oxygen and creates singlet oxygen molecules or reactive oxygen species (ROS), which can lead to tumor cell death. Furthermore, one of the main approches in the prevention and treatment of various cancers is plant compounds application. Phenolic compounds are essential class of natural antioxidants, which play crucial biological roles such as anticancer effects. It was previously suggested that flavonoid such as rutoside could acts as pro-oxidant or antioxidant. Hence, in this study, we aimed to investigate the effect of rutoside on the combination therapy with methylene blue (MB) assisted by photodynamic treatment (PDT) using red light source (660 nm; power density: 30 mW/cm2) on A375 human melanoma cancer cells. METHODS: For this purpose, the A375 human melanoma cancer cell lines were treated by MB-PDT and rutoside. Clonogenic cell survival, MTT assay, and cell death mechanisms were also determined after performing the treatment. Subsequently, after the rutoside treatment and photodynamic therapy (PDT), cell cycle and intracellular reactive oxygen species (ROS) generation were measured. RESULTS: The obtained results showed that, MB-PDT and rutoside had better cytotoxic and antiprolifrative effects on A375 melanoma cancer cells compared to each free drug, whereas the cytotoxic effect on HDF human dermal fibroblast cell was not significant. MB-PDT and rutoside combination induced apoptosis and cell cycle arrest in the human melanoma cancer cell line. Intracellular ROS increased in A375 cancer cell line after the treatment with MB-PDT and rutoside. CONCLUSION: The results suggest that, MB-PDT and rutoside could be considered as novel approaches as the combination treatment of melanoma cancer.
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BACKGROUND: Meteorin-like (Metrnl) is an adipokine with insulin sensitizing and anti-inflammatory properties that has been discovered recently. The relation among Metrnl, Inflammatory Bowel Disease (IBD), and obesity has been unexplored yet. METHODS: The present study was conducted on 54 healthy control, 42 Ulcerative Colitis (UC), and 43 Crohn's disease (CD) patients who were diagnosed by pathological examination. In all participants, serum levels of adiponectin, Metrnl, interleukin (IL)-6, and Tumor necrosis factor (TNF-α) were measured using ELISA kits. RESULTS: Metrnl concentration was considerably lower in both UC (85.25 ± 36.55 pg/mL) and CD (76.93 ± 27.92 pg/mL) patients in comparison to control (107.52 ± 35.33 pg/mL). In addition, it was seen that both patient groups have a decreased level of adiponectin compared to the controls. Besides that, the level of IL-6 and TNF-α were significantly greater in the patient groups. Moreover, the result showed that the level of Metrnl is inversely correlated with body mass index (BMI) in the controls and the patients. Metrnl levels are also inversely associated with IL-6, and TNF-α in both of the patient groups. CONCLUSIONS: The current study is the first one reporting the decreased levels of Metrnl in serum among patients with IBD, which is inversely related with BMI, TNF-α, and IL-6. These results suggested a possible relation of Metrnl with the pathogenesis of IBD, particularly through inflammatory process, although further studies are warranted to dissect the possible mechanism.
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Adipoquinas/sangre , Enfermedades Inflamatorias del Intestino/sangre , Interleucina-6/sangre , Factor de Necrosis Tumoral alfa/sangre , Adulto , Índice de Masa Corporal , Estudios de Casos y Controles , Colitis Ulcerosa/sangre , Enfermedad de Crohn/sangre , Femenino , Humanos , Inflamación/sangre , MasculinoRESUMEN
Leukemia is a malignant hematological disease and chemotherapy remains the most important tool for its treatment. As chemotherapy has many side effects and could lead to resistance in cancer cells, plant-based medication is being considered as a new strategy in cancer treatment. Datura innoxia from the Solanaceae family is used in traditional medicine. The present study investigated the effect of an aqueous extract of D. innoxia aqueous leaf-extract on human chronic myeloid leukemia cells (K562 cell line) and human B lymphoblastoid cells (FS-2 cells) as the noncancerous cell line. The interaction of the D. innoxia extract with double-stranded DNA and histones was studied using multiple spectroscopic techniques. The total phenolic and flavonoid contents were determined through colorimetric analysis and the major polyphenols were quantified by HPLC-DAD analysis. The results demonstrated that the D. innoxia extract inhibited proliferation of the K562 cell line in a dose- and time-dependent manner (IC50 = 0.6 mg/ml), but had a slightly toxic effect on human B lymphoblastoid cells. The spectroscopy results suggest that the D. innoxia extract interacted with both DNA and histones in solution and that D. innoxia could be suggested as an anticancer drug.
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Antineoplásicos Fitogénicos/farmacología , Datura/química , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Extractos Vegetales/farmacología , Polifenoles/farmacología , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Linfocitos B/metabolismo , Línea Celular , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Flavonoides/química , Flavonoides/aislamiento & purificación , Humanos , Concentración 50 Inhibidora , Células K562 , Fenoles/química , Fenoles/aislamiento & purificación , Extractos Vegetales/administración & dosificación , Hojas de la Planta , Polifenoles/administración & dosificación , Polifenoles/aislamiento & purificación , Factores de TiempoRESUMEN
Coronary artery disease (CAD) is the leading cause of death worldwide. Atherosclerosis as the main underlying mechanism of CAD is associated with inflammation and adipose tissue dysfunction. C1q/TNF-related protein12 (CTRP12) is a newly discovered adipokine which is a paralog of adiponectin. CTRP12 has anti-inflammatory and insulin sensitizing effects. Circulating levels of this adipokine have been reported to be lower in patients with type 2 diabetes and women with polycystic ovarian syndrome. The present study was undertaken for the first time to evaluate serum levels of CTRP12 in CAD patients and its association with anthropometric and biochemical parameters. Serum levels of CTRP12 were measured using ELISA kit in 188 CAD patients (angiography confirmed) and 70 controls. The serum levels of adiponectin, TNF-α and IL-6 were measured using ELISA kits. Serum levels of CTRP12 were found to be lower in CAD patients (585.48⯱â¯201.67â¯pg/mL) than in the controls (814.86⯱â¯247.85â¯pg/mL; pâ¯<â¯0.001). CTRP12 also showed an independent association with the risk of CAD (OR [CI]â¯=â¯0.998 [0.996-0.999]; pâ¯=â¯0.019). Moreover, it showed an inverse correlation with HOMA-IR (râ¯=â¯-0.298; pâ¯=â¯0.012) and TNF-α (râ¯=â¯-0.269; pâ¯=â¯0.023) and a positive correlation with adiponectin (râ¯=â¯0.344; pâ¯=â¯0.003) in the controls. In CAD patients, CTRP12 was inversely correlated with BMI (râ¯=â¯-0.181, pâ¯=â¯0.013), HOMA-IR (râ¯=â¯-0.199; pâ¯=â¯0.006), TNF-α (râ¯=â¯-0.259; pâ¯<â¯0.001) and IL-6 (râ¯=â¯-320; pâ¯<â¯0.001) and a positive correlation with high density lipoprotein-cholesterol(râ¯=â¯0.342; pâ¯<â¯0.001) and adiponectin (râ¯=â¯0.398; pâ¯<â¯0.001). The present study showed for the first time that serum levels of CTRP12 are independently associated with CAD and that CTRP12 is associated with several CAD risk factors. The results suggest a possible link between CTRP12 and pathogenic mechanisms of atherosclerosis, such as inflammation and high density lipoprotein-cholesterol metabolism; however, more study is required in this regard.
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Adipoquinas/sangre , Enfermedad de la Arteria Coronaria/sangre , Citocinas/sangre , Resistencia a la Insulina , Anciano , Femenino , Humanos , Inflamación/sangre , Masculino , Persona de Mediana EdadRESUMEN
Curcumin and salicylic acid are both phenolic compounds and they can both affect cancer treatment efficacy. In this study, the effects of methylene blue-curcumin (CU-MB) and methylene blue-salicylic acid (SA-MB) ion pair complexes on MDA-MB-231 human breast cancer cells are studied. According to the thermodynamic parameters, the stability of curcumin and salicylic acid complexes ion pair complexes was compared. The free energy of ion pair interactions was calculated based on binding constants. A comparison of the free energies of the complexes (CU-MB: ∆G°b1 = - 21.11 kJ/mol and ∆G°b2 = - 8.37 kJ/mol, SA-MB: ∆G°b1 = - 12.92 kJ/mol and ∆G°b2 = - 9.02 kJ/mol) indicates that the interaction of methylene blue in first binding interaction with curcumin is greater than that of methylene blue with salicylic acid. Electrostatic interactions are the main forces in the binding of both compounds to methylene blue. All forces are inter-molecular physical interactions. The results of cellular experiments show that ion pairing has enhanced the reduction of cell viability. By increasing molecular stability and prevention of dimerization of methylene blue, the cell killing potential of methylene blue increases and it subsequently causes enhancement of photodynamic efficacy.
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Neoplasias de la Mama/patología , Curcumina/farmacología , Azul de Metileno/farmacología , Fenoles/farmacología , Fotoquimioterapia , Ácido Salicílico/farmacología , Apoptosis/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Muerte Celular/efectos de la radiación , Línea Celular Tumoral , Forma de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Femenino , Humanos , Iones , Luz , Fármacos Fotosensibilizantes/farmacología , Análisis Espectral , TermodinámicaRESUMEN
Nowadays, obesity is considered as a serious and growing global health problem. It is documented that the overweight and obesity are major risk factors for a series of noncommunicable diseases, and in recent years, the obesity-cancer link has received much attention. Numerous epidemiological studies have shown that obesity is associated with increased risk of several cancer types, including colon, breast, endometrium, liver, kidney, esophagus, gastric, pancreatic, gallbladder, and leukemia, and can also lead to poorer treatment. We review here the epidemiological and experimental evidences for the association between obesity and cancer. Specifically, we discuss potential mechanisms focusing how dysfunctional angiogenesis, chronic inflammation, interaction of proinflammatory cytokines, endocrine hormones, and adipokines including leptin, adiponectin insulin, growth factors, estrogen, and progesterone and strikingly, cell metabolism alteration in obesity participate in tumor development and progression, resistance to chemotherapy, and targeted therapies such as antiangiogenic and immune therapies.
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Neoplasias/metabolismo , Obesidad/metabolismo , Animales , Modelos Animales de Enfermedad , Humanos , Modelos Biológicos , Neoplasias/epidemiología , Obesidad/epidemiologíaRESUMEN
[This retracts the article DOI: 10.1039/D1RA01256H.].
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In this study, we aimed to investigate the effect of the co-treatment with apigenin and doxorubicin (DOX) on K562 cells. Our results show that apigenin (0, 40, 60, 80 ,100 µM) and DOX (0-10 µM) as single therapy, could decrease K562 cell viability (after 24 h of treatment) in a dose-dependent manner. Additionally, the co-treatment with apigenin (60, 80 µM) and 10 µM of DOX led to a greater reduction in cell growth (CI: 0.92 and 0.97) after 24 h of treatment compared to the single DOX treatment (p < 0.05). Consequently, apigenin and DOX, either as single or as co-treatment (24 h of treatment), were indicated to induce apoptosis in K562 cells through morphological studies, RT-qPCR, and western-blot analysis. Eventually, the expressions of Caspase 3, 6, 7, and 9 genes in the single treatment with DOX had higher alteration compared to the co-treatment with DOX and apigenin (p < 0.05).
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BACKGROUND AND METHODS: Colorectal cancer (CRC) is considered one of the most common malignancies worldwide. The diagnosis and prognosis of the patients are very poor. In this study, we used in-silico analysis and experimental techniques to investigate novel co-expression genes and their associated miRNA networks in CRC. For this purpose, we conducted a comprehensive transcriptome analysis using online bulk and single-cell RNA-seq datasets. We then validated the results on tissue samples from cancerous and adjacent normal tissues from CRC patients by RT-qPCR. RESULTS: Using a weighted gene co-expression network algorithm, we identified SLC4A4 as a significantly downregulated hub gene in the CRC. The single-cell analysis indicated that the expression level of SLC4A4 in Paneth cells is higher than in other cell populations. Further computational analysis suggested hsa-miR-223-3p and hsa-miR-106a-5p as two specific hub-miRNAs for the SLC4A4 gene. RT-qPCR analysis showed a 2.60-fold downregulation of SLC4A4. Moreover, hsa-miR-223-3p and hsa-miR-106a-5p showed an increased expression level of 5.58-fold and 9.66-fold in CRC samples, respectively. Based on the marginal model analysis, by increasing the expression of hsa-miR-106a-5p, the average expression of the SLC4A4 gene significantly decreased by 103 units. Furthermore, ROC curves analysis indicated statistically significant for diagnostic ability of SLC4A4 (AUC: 0.94, Sensitivity: 95.5%, Specificity: 95.5%) and hsa-miR-106a-5p (AUC: 0.72, Sensitivity: 72.7%, Specificity: 100%). CONCLUSION: This study provides a framework of co-expression gene modules and miRNAs of CRC, which identifies some important biomarkers for CRC pathogenicity and diagnosis. Further experimental evidence will be required to support this study and validate the precise molecular pathways.
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Adenocarcinoma , Neoplasias Colorrectales , MicroARNs , Humanos , Irán , MicroARNs/genética , Perfilación de la Expresión Génica , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Expresión Génica , Simportadores de Sodio-Bicarbonato/genéticaRESUMEN
BACKGROUND: Gastric cancer (GC) is the world's second-leading cause of cancer-related mortality, continuing to make it a serious healthcare concern. Even though the prevalence of GC reduces, the prognosis for GC patients remains poor in terms of a lack of reliable biomarkers to diagnose early GC and predict chemosensitivity and recurrence. METHODS AND MATERIAL: We integrated the gene expression patterns of gastric cancers from four RNAseq datasets (GSE113255, GSE142000, GSE118897, and GSE130823) from Gene Expression Omnibus (GEO) database to recognize differentially expressed genes (DEGs) between normal and GC samples. A gene co-expression network was built using weighted co-expression network analysis (WGCNA). Furthermore, RT-qPCR was performed to validate the in silico results. RESULTS: The red modules in GSE113255, Turquoise in GSE142000, Brown in GSE118897, and the green-yellow module in GSE130823 datasets were found to be highly correlated with the anatomical site of GC. ITGAX, CCL14, ADHFE1, and HOXB13) as the hub gene are differentially expressed in tumor and non-tumor gastric tissues in this study. RT-qPCR demonstrated a high level of the expression of this gene. CONCLUSION: The expression levels of ITGAX, CCL14, ADHFE1, and HOXB13 in GC tumor tissues are considerably greater than in adjacent normal tissues. Systems biology approaches identified that these genes could be possible GC marker genes, providing ideas for other experimental studies in the future.
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Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica/genética , Neoplasias Gástricas , Oxidorreductasas de Alcohol/análisis , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Quimiocinas CC/análisis , Biología Computacional/métodos , Detección Precoz del Cáncer/métodos , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes , Proteínas de Homeodominio/análisis , Humanos , Proteínas Mitocondriales/análisis , Pronóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND: Nephropathy diabetes is one of the important causes of death and a more prevalent cause of end-stage renal disease. OBJECTIVE: The present study investigated the effect of applying spironolactone and captopril and their combination on some renal performance indices and cholesterol-efflux-related gene expression in nephropathy diabetic rats. METHODS: Intraperitoneal injection of streptozotocin was used to induce diabetes in rats. FBS, creatinine, and BUN were assayed using the calorimetry technique; also, urine microalbumin was assayed by ELISA. Hepatic gene expressions of ABCA1, ABCG1, and miR-33 were evaluated by the real-time PCR method. RESULTS: FBS levels in the captopril-treated group were significantly decreased compared with the untreated diabetic group. BUN levels of treated groups with captopril and a combination of captopril + spironolactone were significantly increased. GFR of both treated diabetic groups with captopril and spironolactone was significantly lower than an untreated diabetic group. ABCA1 gene expression in hepatic cells of the combination of spironolactone + captopril treated group was significantly increased compared to other treated and untreated diabetic groups. The hepatic expression of the ABCG1 gene in the treated and untreated diabetic groups was significantly lower than in the control group. Treatment of the diabetic group with only combination therapy decreased the hepatic gene expression of miR-33 significantly. CONCLUSION: Obtained results suggest that S+C combination therapy can improve nephropathy and diabetes disorders by targeting the ABCA1 and miR-33 gene expression. It is suggested that miR-33 and ABCA1 genes evaluation could be a new therapeutic strategy for nephropathy diabetes remediation.
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Diabetes Mellitus Experimental , Nefropatías Diabéticas , MicroARNs , Transportador 1 de Casete de Unión a ATP , Animales , Captopril/metabolismo , Captopril/farmacología , Captopril/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Riñón , MicroARNs/metabolismo , Ratas , Ratas Wistar , Espironolactona/metabolismo , Espironolactona/farmacología , Espironolactona/uso terapéuticoRESUMEN
BACKGROUND: Several serious attempts to treat colorectal cancer have been made in recent decades. However, no effective treatment has yet been discovered due to the complexities of its etiology. METHODS: we used Weighted Gene Co-expression Network Analysis (WGCNA) to identify key modules, hub-genes, and mRNA-miRNA regulatory networks associated with CRC. Next, enrichment analysis of modules has been performed using Cluepedia. Next, quantitative real-time PCR (RT-qPCR) was used to validate the expression of selected hub-genes in CRC tissues. RESULTS: Based on the WGCNA results, the brown module had a significant positive correlation (r = 0.98, p-value=9e-07) with CRC. Using the survival and DEGs analyses, 22 genes were identified as hub-genes. Next, three candidate hub-genes were selected for RT-qPCR validation, and 22 pairs of cancerous and non-cancerous tissues were collected from CRC patients referred to the Gastroenterology and Liver Clinic. The RT-qPCR results revealed that the expression of GUCA2B was significantly reduced in CRC tissues, which is consistent with the results of differential expression analysis. Finally, top miRNAs correlated with GUCA2B were identified, and ROC analyses revealed that GUCA2B has a high diagnostic performance for CRC. CONCLUSIONS: The current study discovered key modules and GUCA2B as a hub-gene associated with CRC, providing references to understand the pathogenesis and be considered a novel candidate to CRC target therapy.
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Neoplasias Colorrectales/genética , Proteínas Activadoras de la Guanilato-Ciclasa/genética , Apoptosis/fisiología , Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica/fisiología , Redes Reguladoras de Genes , Humanos , Mucosa Intestinal/fisiología , MicroARNs/biosíntesis , Péptidos Natriuréticos/metabolismo , TranscriptomaRESUMEN
A heterogeneous, magnetically recoverable nanocomposite, Fe3O4@NFC@ONSM-Ni(ii) was prepared by immobilization of a novel Ni(ii) Schiff base complex on Fe3O4@NFC nanoparticles followed by treatment with melamine. This trinuclear catalyst has been characterized using several analytical techniques including FT-IR, TEM, Fe-SEM, EDX, DLS, ICP, TGA, VSM, and XRD. It was used as an efficient catalyst for one-pot solvent-free synthesis of 1,4-dihydropyridine and poly-hydro quinoline derivatives through Hantzsch reaction. This catalyst showed remarkable advantage over previously reported catalysts due to suitable conditions, short reaction time, high efficiency and lower catalyst load and timely recovery of the magnetic catalyst. Moreover, the effects of Fe3O4@NFC@ONSM-Ni(ii) nanoparticles on the in vitro proliferation of human leukemia cell line (k562) and human breast cancer cells (MDA-MB-231) were investigated. The results of MTT and Hochest assays suggested that the nanoparticles could effectively inhibit the proliferation of these cancer cells in a time- and concentration-dependent manner.
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Antimicrobial photodynamic therapy (aPDT) has drawn increasing attention for its potential to effectively kill multidrug-resistant pathogenic bacteria and also for its low tendency to induce drug resistance. Antimicrobial photodynamic therapy (aPDT) is the application of photoactive dye followed by light irradiation that leads to the death of microbial cells mainly by reactive oxygen species (ROS) production in the presence of oxygen molecules. Methylene Blue (MB) as a photosensitizer is a hydrophobic drug molecule and prone to aggregation and dimer formation which lead to its low phototoxicity. Rutin, a flavonoid compound which is derived from plants such as wheat, apple, and tea has many properties such as antibacterial activity. In this study, we investigated the effect of rutin as a flavonoid compound on photodynamic inactivation by MB on Pseudomonas aeruginosa and Staphylococcus aureus. After performing the Minimum Inhibitory Concentration (MIC) assay (to measure minimum inhibitory concentration) and the MTT assay (to evaluate methylene blue toxicity), the effect of aPDT at 660â¯nm and pretreatment or post treatment with rutin on bacteria in the forms of planktonic and biofilm were investigated. The results showed that by a combination of rutin (800⯵g/mL) with methylene blue (MB 8⯵g/mL) as a photosensitizer and aPDT (660â¯nm, 5â¯min), there is a more reduction in the number of bacteria in the planktonic condition and bacterial biofilm production in comparison to MB alone. MB-aPDT showed no toxic effect against human dermal fibroblast with the proposed strategy which could suggest its application with rutin as a novel approach in the treatment of bacteria in wound infection.
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Staphylococcus aureus Resistente a Meticilina , Fotoquimioterapia , Biopelículas , Flavonoides , Humanos , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Pseudomonas aeruginosa , Rutina/farmacología , Staphylococcus aureusRESUMEN
Datura innoxia (D. innoxia) has an extensive usage in traditional medicine and can also be used for intervention therapy in order to treat cancer. Despite of accomplishing some researches on D. innoxia mechanism, still our knowledge is very little about exact D. innoxia apoptotic mechanism on human chronic myeloid leukemia cells (K562 cells). This study purpose was to clarify the molecular mechanism of apoptosis, which was mediated by D. innoxia leaves aqueous extract in K562 cells. MTT assay and flow cytometry was applied in order to assess the viability and apoptosis induction of K562 cells and normal human lymphoid B cells in the D. innoxia presence. Finally, the expression of the apoptotic related genes (p53, BAX, BCL2, Caspases 3, 6, 7 and 9) were evaluated using quantitative Real-Time PCR. Western blot analysis was applied for assessing the protein expression. MTT results indicated that D. innoxia could inhibit the viability of K562 cells in a dose- and time-dependent manner. In parallel, D. innoxia inhibitory effect on normal human lymphoid B cells was lower in comparison with its effect on K562 cells at the same concentrations and same incubation time. Apoptosis induction in K562 cells after D. innoxia exposure was determined by flow cytometry. Apoptosis was activated by D. innoxia in K562 cells throughout increasing the expression of P53, BAX/BCL2 ratio, caspase 9, 3, 6, 7. Western blot analysis demonstrated significant increase in cleaved PARP-1 and cleaved caspase 3 in treated K562 cells with high D. innoxia leaves aqueous extract concentration. D. innoxia leaves trigger apoptosis in K562 cells throughout intrinsic apoptotic pathway.Communicated by Ramaswamy H. Sarma.
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Datura , Leucemia Mielógena Crónica BCR-ABL Positiva , Apoptosis , Proliferación Celular , Humanos , Células K562 , Hojas de la PlantaRESUMEN
BACKGROUND: Atherosclerosis as a progressive inflammatory disease is the main cause of Coronary Artery Disease (CAD). Multiple genetic and environmental factors are involved in susceptibility to atherosclerotic vascular diseases. FOXO1 gene acts as a key molecular proinflammatory transcription factor and the FBOX32 gene as an F-box protein plays pivotal roles in regulation of muscle atrophy and inhibition of the pathologic cardiac hypertrophy. MiR-27a has been reported to contribute to atherosclerosis prevention and the inflammatory processes of atherosclerosis. MicroRNA-23a has been found to promote atherosclerotic plaque progression and vulnerability. Hence, given the importance of these subjects, the present study was carried out to investigate the expression levels of the desired genes. METHODOLOGY: In this case-control study, 82 patients with CAD and 80 healthy controls were investigated. Expression levels of miRNAs -27a and 23a, FOXO1, Sirtuin 1 (SIRT1) in the Peripheral Blood Mononuclear Cells (PBMCs), serum concentration of IL6 and TNF-α of the studied subjects were evaluated using the real-time Polymerase Chain Reaction (PCR) technique. The correlation between the variables was also investigated. RESULTS: Results of the study demonstrated that expression of FOXO1, IL-6, TNF-α, miR-27a, and miR-23a increased in the PBMCs of the patients with CAD and their expression levels were significantly correlated with the severity of stenosis. A significant decrease was observed in the expression of SIRT1 in the patients with CAD compared to the healthy controls. Furthermore, the Receiver Operating Characteristic (ROC) curve was plotted to find the effectiveness of FOXO1 and miRNA-27a gene expression as a diagnostic marker for CAD. CONCLUSIONS: Findings of the study suggested that miRs-27a and FOXO1 genes have a potential role in the progression of atherosclerosis and mediate the molecular and genetic disturbances of the intracellular communication in the atherosclerosis.