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1.
Nat Prod Res ; : 1-12, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501578

RESUMO

Cytotoxicity-guided purification of Juniperus polycarpos K. Koch leaves (Cupressaceae) led to the isolation of a new labdane diterpenoid, 3-(acetyloxy)-acetylisocupressic acid (1), together with isocupressic acid (2), 3,4-dimethoxycinnamoyl alcohol (3) and deoxypodophyllotoxin (4). The chemical structures of 1-4 were established by detailed 1D and 2D NMR, HRFAB-MS and LRESI-MS, as well as by comparing the spectral data with those reported in the literature. Compound 1 was ineffective against HepG2 cells and protease enzyme, while 2 showed potent cytotoxicity against HepG2 cells (IC50 of 3.73 µg/mL) compared to cisplatin (IC50 of 12.65 µg/mL). Computational analyses with CDK1 protein (a prominent protein in the cell cycle of HepG2 cells) revealed the binding affinity of 2 (-31.86 kcal/mol) was better than 1 (-19.70 kcal/mol) because the acetoxy groups did not allow binding deeply to the ATP binding site. Compounds 2 and 4 moderately inhibited the protease activity (IC50 = 52.7 and 63.0 µg/mL, respectively). Further in vitro and in vivo studies on the plant are strongly recommended.

2.
Heliyon ; 10(3): e25256, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38333789

RESUMO

Diabetes is a dangerous metabolic disorder by increasing incidence in human societies worldwide. Recently, much attention has been focused on the development of hypoglycemic agents, particularly the derivatives of herbal drugs, in the treatment of diabetes. This research aimed to study the anti-diabetic effect of Salvia mirzayanii in the diabetic rat models. First, the plant material was extracted from the leaves, and orally administered to the rats. After treating the animals with the aqueous extract of S. mirzayanii at a dose of 600 mg/kg, animal body weight for 12 weeks, fasting blood glucose, oral glucose tolerance test (OGTT), and body weight changes were examined. To analyze the anti-diabetic function of S. mirzayanii, we measured the expression of glucose transporter-4 (GLUT4), phosphoenolpyruvate carboxykinase (PEPCK), and glucose 6-phosphatase (G6Pase) genes in healthy and streptozotocin (STZ)-diabetic rats. The expression levels of the genes of interest in muscle and liver tissues were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). There were no significant differences in fasting blood glucose and OGTT between normal control (NC) group and the diabetic control (DC) group treated with S. mirzayanii. In contrast, there was a significant difference with the untreated DC (P < 0.05). The treatment of diabetic rats with S. mirzayanii significantly increased the expression of GLUT4 in the muscle and decreased the expression levels of PEPCK and G6Pase in the liver compared to the DC group (P < 0.05). These findings clearly show that S. mirzayanii can improve hyperglycemia by increasing the GLUT4 expression, and inhibiting the gluconeogenesis pathway in the liver. In general, the obtained results provided a new insight into the efficacy of S. mirzayanii aqueous extract as an anti-diabetic herbal medicine.

3.
Crit Rev Food Sci Nutr ; 63(28): 9163-9186, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35468007

RESUMO

Various studies, especially in recent years, have shown that quercetin has beneficial therapeutic effects in various human diseases, including diabetes. Quercetin has significant anti-diabetic effects and may be helpful in lowering blood sugar and increasing insulin sensitivity. Quercetin appears to affect many factors and signaling pathways involved in insulin resistance and the pathogenesis of type 2 of diabetes. TNFα, NFKB, AMPK, AKT, and NRF2 are among the factors that are affected by quercetin. In addition, quercetin can be effective in preventing and ameliorating the diabetic complications, including diabetic nephropathy, cardiovascular complications, neuropathy, delayed wound healing, and retinopathy, and affects the key mechanisms involved in the pathogenesis of these complications. These positive effects of quercetin may be related to its anti-inflammatory and anti-oxidant properties. In this article, after a brief review of the pathogenesis of insulin resistance and type 2 diabetes, we will review the latest findings on the anti-diabetic effects of quercetin with a molecular perspective. Then we will review the effects of quercetin on the key mechanisms of pathogenesis of diabetes complications including nephropathy, cardiovascular complications, neuropathy, delayed wound healing, and retinopathy. Finally, clinical trials investigating the effect of quercetin on diabetes and diabetes complications will be reviewed.


Assuntos
Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Doenças Retinianas , Humanos , Quercetina/farmacologia , Quercetina/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/prevenção & controle , Complicações do Diabetes/metabolismo , Doenças Retinianas/tratamento farmacológico
4.
Biochimie ; 209: 20-36, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36535545

RESUMO

Inflammatory bowel disease is a chronic inflammatory disease and has periods of recurrence and remission. Improper immune responses to gut flora bacteria, along with genetic susceptibility, appear to be involved in causing this complex disease. It seems dysbiosis and oxidative stress may also be involved in IBD pathogenesis. A significant number of clinical studies have shown an interesting association between sleep disturbances and IBD. Studies in animal models have also shown that sleep deprivation has a significant effect on the pathogenesis of IBD and can aggravate inflammation. These interesting findings have drawn attention to melatonin, a sleep-related hormone. Melatonin is mainly produced by the pineal gland, but many tissues in the body, including the intestines, can produce it. Melatonin can have an interesting effect on the pathogenesis of IBD. Melatonin can enhance the intestinal mucosal barrier, alter the composition of intestinal bacteria in favor of bacteria with anti-inflammatory properties, regulate the immune response, alleviate inflammation and attenuate oxidative stress. It seems that, melatonin supplementation is effective in relieving inflammation and healing intestinal ulcers in IBD animal models. Some clinical studies have also shown that melatonin supplementation as an adjuvant therapy may be helpful in reducing disease activity in IBD patients. In this review article, in addition to reviewing the effects of sleep disturbances and melatonin on key mechanisms involved in the pathogenesis of IBD, we will review the findings of clinical studies regarding the effects of melatonin supplementation on IBD treatment.


Assuntos
Doenças Inflamatórias Intestinais , Melatonina , Animais , Melatonina/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Intestinos , Mucosa Intestinal/patologia , Inflamação/tratamento farmacológico , Bactérias
5.
Crit Rev Food Sci Nutr ; : 1-24, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36345891

RESUMO

Inflammatory bowel disease (IBD) is a long-life disease with periods of recurrence and relief. Oxidative stress plays an important role in the pathogenesis of this disease. Recent years' studies in the field of IBD treatment mostly have focused on targeting cytokines and immune cell trafficking using antibodies and inhibitors, altering the composition of intestinal bacteria in the line of attenuation of inflammation using probiotics and prebiotics, and attenuating oxidative stress through antioxidant supplementation. Studies in animal models of IBD have shown that some polyphenolic compounds including curcumin, quercetin, resveratrol, naringenin, and epigallocatechin-3-gallate can affect almost all of the above aspects and are useful compounds in the treatment of IBD. Clinical studies performed on IBD patients have also confirmed the findings of animal model studies and have shown that supplementation with some of the above-mentioned polyphenolic compounds has positive effects in reducing disease clinical and endoscopic activity, inducing and maintaining remission, and improving quality of life. In this review article, in addition to a detailed reviewing the effects of the above-mentioned polyphenolic compounds on the events involved in the pathogenesis of IBD, the results of these clinical studies will also be reviewed.

6.
Cancer Cell Int ; 22(1): 146, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35410210

RESUMO

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disease with relapse and remission periods. Ulcerative colitis and Crohn's disease are two major forms of the disease. IBD imposes a lot of sufferings on the patient and has many consequences; however, the most important is the increased risk of colorectal cancer, especially in patients with Ulcerative colitis. This risk is increased with increasing the duration of disease, thus preventing the progression of IBD to cancer is very important. Therefore, it is necessary to know the details of events contributed to the progression of IBD to cancer. In recent years, the importance of miRNAs as small molecules with 20-22 nucleotides has been recognized in pathophysiology of many diseases, in which IBD and colorectal cancer have not been excluded. As a result, the effectiveness of these small molecules as therapeutic target is hopefully confirmed. This paper has reviewed the related studies and findings about the role of miRNAs in the course of events that promote the progression of IBD to colorectal carcinoma, as well as a review about the effectiveness of some of these miRNAs as therapeutic targets.

7.
Artigo em Inglês | MEDLINE | ID: mdl-35295927

RESUMO

Anthocyanins are components of the flavonoid group with different properties, such as antidiabetic properties. This study aimed to isolate anthocyanin from Berberis integerrima Bunge fruits and evaluate α-amylase and α-glucosidase inhibition by this mentioned anthocyanin. The anthocyanin of Berberis integerrima fruit was isolated using column chromatography, and the antidiabetic properties of the anthocyanin were determined by the levels of α-amylase and α-glucosidase inhibition. Km and Vmax were also evaluated using the GraphPad Prism 7. The results of this study showed that the anthocyanin content of the fruit extract was 14.36 ± 0.33 mg/g, and following purification, this amount increased to 34.51 ± 0.42 mg/g. The highest of α-glucosidase inhibition was observed in the purified anthocyanin with IC50 = 0.71 ± 0.085 mg/ml, compared to acarbose as the baseline with IC50 = 8.8 ± 0.14 mg/ml, p < 0.0001. Purified anthocyanin of the mentioned fruit with IC50 = 1.14 ± 0.003 mg/ml had the greatest α-amylase inhibition, which was similar to acarbose as the standard with IC50 = 1 ± 0.085 mg/ml, p < 0.05. The inhibition of α-glucosidase and α-amylase by purified anthocyanin showed uncompetitive inhibition, and the enzyme inhibition by unpurified anthocyanin showed mixed inhibition. The obtained findings showed that Berberis integerrima fruit can be mentioned as a source of anthocyanin with antidiabetic properties.

8.
Cell J ; 24(1): 44-50, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35182064

RESUMO

OBJECTIVE: The present study investigated the role of miR-181a as a small non-coding RNA molecule in acute myeloid leukemia (AML) pathogenesis and reflected on the effects of Sulforaphane (SFN) on AML progression. MATERIALS AND METHODS: This experimental study had two parts. In vivo study, the miR-181a levels was measured in patients with symptoms of AML and compared to healthy controls (HCs) to investigate its role in AML pathogenesis. Afterward, an in vitro study was performed to examine the effects of SFN on the growth, apoptosis and proliferation rate of AML cell lines. Finally, the effect of SFN on miR-181a was evaluated as a major miRNA involved in hematopoiesis. RESULTS: The results of this study showed an increasing trend (2.9-fold, P=0.0019) in miR-181a expression levels in AML patients as compared with HCs. The data associated with MTT assay and flow cytometry (FCM) additionally demonstrated the anti-proliferative effects of SFN against AML cell lines, with a reduction in miR-181a levels. As well, no significant difference was noted between 24 hours and 48 hours treatments by SFN. It was deduced that modulation of miR-181a expression levels could be one of the mechanisms associated with the anti-proliferative effects of SFN against AML. CONCLUSION: MiR-181a levels contribute to AML pathogenesis and thus they can be considered as a strategy in controlling AML progression in patients. Accordingly, SFN can arrest cell proliferation and induce apoptosis in AML cell lines through retardation expression of miR-181a and affecting miR-181a pathway, which already clarified its role in the differentiation of hematopoietic stem cells and indicates another mode of anti-cancer action of sulforaphane.

9.
Biol Trace Elem Res ; 200(6): 2556-2571, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34368933

RESUMO

Influenza viruses, respiratory syncytial virus (RSV), and SARS-COV2 are among the most dangerous respiratory viruses. Zinc is one of the essential micronutrients and is very important in the immune system. The aim of this narrative review is to review the most interesting findings about the importance of zinc in the anti-viral immune response in the respiratory tract and defense against influenza, RSV, and SARS-COV2 infections. The most interesting findings on the role of zinc in regulating immunity in the respiratory tract and the relationship between zinc and acute respiratory distress syndrome (ARDS) are reviewed, as well. Besides, current findings regarding the relationship between zinc and the effectiveness of respiratory viruses' vaccines are reviewed. The results of reviewed studies have shown that zinc and some zinc-dependent proteins are involved in anti-viral defense and immune regulation in the respiratory tract. It seems that zinc can reduce the viral titer following influenza infection. Zinc may reduce RSV burden in the lungs. Zinc can be effective in reducing the duration of viral pneumonia symptoms. Zinc may enhance the effectiveness of hydroxychloroquine in reducing mortality rate in COVID-19 patients. Besides, zinc has a positive effect in preventing ARDS and ventilator-induced lung damage. The relationship between zinc levels and the effectiveness of respiratory viruses' vaccines, especially influenza vaccines, is still unclear, and the findings are somewhat contradictory. In conclusion, zinc has anti-viral properties and is important in defending against respiratory viral infections and regulating the immune response in the respiratory tract.


Assuntos
COVID-19 , Influenza Humana , Síndrome do Desconforto Respiratório , Oligoelementos , Vírus , Humanos , RNA Viral , SARS-CoV-2 , Oligoelementos/uso terapêutico , Zinco/farmacologia
10.
J Cell Physiol ; 236(8): 5512-5532, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33580511

RESUMO

In cancerous cells, significant changes occur in the activity of signaling pathways affecting a wide range of cellular activities ranging from growth and proliferation to apoptosis, invasiveness, and metastasis. Extensive changes also happen with respect to the metabolism of a cancerous cell encompassing a wide range of functions that include: nutrient acquisition, biosynthesis of macromolecules, and energy generation. These changes are important and some therapeutic approaches for treating cancers have focused on targeting the metabolism of cancerous cells. Oncogenes and tumor suppressor genes have a significant effect on the metabolism of cells. There appears to be a close interaction between metabolism and the signaling pathways in a cancerous cell, in which the interaction provides the metabolic needs of a cancerous cell for uncontrolled proliferation, resistance to apoptosis, and metastasis. In this review, we have reviewed the latest findings in this regard and briefly review the most recent research findings regarding targeting the metabolism of cancer cells as a therapeutic approach for treatment of cancer.


Assuntos
Apoptose/fisiologia , Proliferação de Células/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proliferação de Células/fisiologia , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Humanos , Metástase Neoplásica/patologia , Neoplasias/metabolismo , Transdução de Sinais/fisiologia
11.
Life Sci ; 259: 118255, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32818543

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies with a significant mortality rate. Despite the great advances in cancer treatment in the last few decades, effective treatment of CRC is still under challenge. One of the main problems associated with CRC treatment is the resistance of cancer cells to chemotherapy drugs. METHODS: Many studies have been carried out to identify CRC chemoresistance mechanisms, and shed light on the role of ATP-binding cassette transporters (ABC transporters), enzymes as thymidylate synthase, some signaling pathways, and cancer stem cells (CSC) in chemoresistance and failed CRC chemotherapies. Other studies have also been recently carried out to find solutions to overcome chemoresistance. Some of these studies have identified the role of miRNAs in chemoresistance of the CRC cells and the effective use of these micro-molecules to CRC treatment. RESULTS: Considering the results of these studies, more focus on miRNAs likely leads to a proper solution to overcome CRC chemoresistance. CONCLUSION: The current study has reviewed the related literature while discussing the efficacy of miRNAs as potential clinical tools for overcoming CRC chemoresistance and reviewing the most important chemoresistance mechanisms in CRC cells.


Assuntos
Neoplasias Colorretais/genética , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica/genética , Humanos , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/metabolismo , Transdução de Sinais/efeitos dos fármacos
12.
Clin Chim Acta ; 510: 556-565, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32818491

RESUMO

The term IBD is usually used for referring to a group of inflammatory gastro-intestinal diseases (mainly Crohn's disease and ulcerative colitis). Accordingly, IBD arises as a result of inappropriate immune response to intestinal commensal organisms among genetically susceptible individuals. Performing colonoscopy and histopathologic evaluation on an inflamed bowel biopsy specimen are currently considered as gold standards for diagnosis and management of IBD. Correspondingly, these techniques are known to be invasive and costly. In recent decades, fecal calprotectin, as a biomarker, has received much attention for the diagnosis and non-invasive management of IBD. Up to now, many studies have investigated the efficacy of fecal calprotectin in the areas of IBD differentiation from IBS, prediction of endoscopic and histologic activities of IBD and prediction of disease recurrence. Although some of these studies have reported promising results, some others have shown significant limitations. Therefore, in this paper, we reviewed the most interesting ones of these studies after a brief discussion of the laboratory measurement of fecal calprotectin. Moreover, we attempted to provide an answer for the question of whether fecal-calprotectin could be considered as a potential surrogate marker for colonoscopy.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Biomarcadores/análise , Colonoscopia , Fezes/química , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Complexo Antígeno L1 Leucocitário
13.
Acta Biomed ; 91(4): e2020106, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33525287

RESUMO

Background Folate is an important vitamin with protective effect against some human diseases. The aim of this study was to evaluate the relationship between serum folate levels, inflammatory markers and disease clinical activity in patients with inflammatory bowel disease (IBD).   Methods The participants were classified into two groups in which 38 IBD patients and 38 healthy controls were studied. Disease clinical activities were evaluated by means of established score systems. Serum folate, homocysteine and C-reactive protein and ESR were measured. Obtained data were analyzed with proper statistical methods and P- value less than 0.05 was considered as statistical significant.   Results The level of serum folate was significantly reduced in IBD patients with active disease compared to patients with clinical remission (p=0.043) and also healthy controls (p = 0.008). Moreover, there was a significant inverse correlation between serum folate levels and C-reactive protein in IBD patients (r = -0.563 p =0.001).         Conclusion Serum folate levels is associated with inflammatory markers and disease clinical activity in IBD patients, therefore there is a possibility that disease clinical activity is reduced with adequate folate level.


Assuntos
Colite , Ácido Fólico , Homocisteína , Doenças Inflamatórias Intestinais , Ácido Fólico/análise , Homocisteína/análise , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Vitamina B 12
14.
J Diabetes Metab Disord ; 19(2): 1593-1598, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33520855

RESUMO

BACKGROUND: The present study designed to evaluate the Serum levels of CMPF, MASP1 and UA in pre-diabetic subjects was compared to normal subjects. METHODS: This research is a case-control study. We studied 44 pre-diabetics with 44 normal subjects and were evaluated serum concentration of CMPF, Masp1 and U.Ain both groups andfurthermore serum concentration FPG, BUN, Cr, Cho, TG, HDLc, LDLc, AST, ALT, ALP, HbA1c was examined and correlation between of CMPF, Masp1 and U.Aand other parameters was statistically analyzed. RESULTS: Serum levels of MASP1, CMPF, fasting plasma glucose (P < 0.001)and uric acid (P < 0.002) were significantly increased in pre-diabetic subjects. In this study, a significant difference was found between MASP1 and CMPF in pre-diabetic subjects compared to normal subjects (P=0.005, r=0.291). There was also a significant difference between serum levels of MASP1 with HbA1C (P=0.01, r=0.269). CONCLUSION: Serum levels of CMPF, MASP1 and uric acid were increased in pre-diabetic subjects. These parameters can be used as a biomarker for the diagnosis of pre-diabetes.

15.
Afr J Lab Med ; 9(1): 1001, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33392049

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder. OBJECTIVE: This study aimed to evaluate red blood cell distribution width (RDW) and mean platelet volume (MPV) as laboratory markers to discriminate IBS patients from both healthy controls and patients with inflammatory bowel disease (IBD). METHODS: This case-control study enrolled patients referred to Ayatollah Rouhani Hospital, Endoscopy Department, Babol, Iran, for colonoscopy examination from 2015 to 2017. Fifty IBS patients were selected from among patients who had undergone a normal colonoscopy and showed symptoms matching the Rome III criteria. Fifty healthy participants and 50 IBD patients, matched for sex and age, were also enrolled in this study. Both RDW and MPV were measured and analysed by independent sample t-test and receiver operating characteristic curve analysis. A p-value of less than 0.05 was considered statistically significant. RESULTS: While RDW was higher and MPV was lower among IBS patients compared to healthy controls (p = 0.047 and p = 0.001), there were no significant differences in RDW or MPV levels between IBS and IBD patients. The area under the curve of RDW in the discrimination between IBS and IBD was 0.620 (p = 0.039), and the area under the curve of MPV in the discrimination between healthy controls and IBS patients was 0.801 (p = 0.001). CONCLUSION: Mean platelet volume is potentially a useful laboratory marker for distinguishing between IBS patients and healthy individuals. Red blood cell distribution width should be considered as a potential marker to distinguish among IBS and IBD patients.

16.
J Cell Physiol ; 234(4): 3277-3293, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30417350

RESUMO

Inflammatory bowel disease (IBD), as a chronic and recurrent inflammatory disorder, is caused by a dysregulated and aberrant immune response to exposed environmental factors in genetically susceptible individuals. Despite huge efforts in determining the molecular pathogenesis of IBD, an increasing worldwide incidence of IBD has been reported. MicroRNAs (miRNAs) are a set of noncoding RNA molecules that are about 22 nucleotides long, and these molecules are involved in the regulation of the gene expression. By clarifying the important role of miRNAs in a number of diseases, their role was also considered in IBD; numerous studies have been performed on this topic. In this review, we attempt to summarize a number of studies and discuss some of the recent developments in the roles of miRNAs in the pathophysiology, diagnosis, and treatment of IBD.


Assuntos
Doenças Inflamatórias Intestinais/genética , Intestinos , MicroRNAs/genética , Animais , Regulação da Expressão Gênica , Marcadores Genéticos , Terapia Genética/métodos , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/terapia , Intestinos/patologia , Intestinos/fisiopatologia , MicroRNAs/metabolismo , MicroRNAs/uso terapêutico , Valor Preditivo dos Testes , Transdução de Sinais , Resultado do Tratamento
17.
Mol Biol Rep ; 45(6): 2491-2499, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30350234

RESUMO

Acute myeloid leukemia (AML) has the highest rate of mortality among the leukemias. Disruption in miRNAs level is involved in the pathogenesis of the disease. The miR-155 has a role in primary differentiation of myeloid progenitor. Meanwhile, there is little knowledge about the effects of sulforaphane against leukemia. The present study tried to evaluate pathologic effect of miR-155 in patients in various subgroups of AML, and then pioneered in assessing miR-155 levels by the effect of sulforaphane in different AML cell lines. The miR-155 level was significantly higher in patients with AML compared to the controls. Interestingly, the increase in miR-155 was converged with raising the subtype of AML (from M1 to M5). The miR-155 levels increased by 1.2 times in patients with M1, but this increase reached 2.5 times in the patients in the M5 subgroup. Sulforaphane reduced the number of live cells and increased the mortality rate of AML cells particularly by induction of apoptosis. However, the anti-proliferative effect of this agent was more dominant and could dose-dependently lessen miR-155 levels in myeloid leukemia cells. More or less, about 80% reduction in miR-155 expression was almost observed after 48 h treatment with 60 µM sulforaphane in all four studied cell lines. The obtained results indicated that miR-155 might function as an oncomir in AML and can potentially be considered as a prognosis biomarker for AML. The anti-cancer effects of sulforaphane can be correlated with reduction of miR-155 levels. These findings suggested that sulforaphane could induce more differentiation in myeloid progenitor cells through controlling the miR-155, thereby mitigating the progress of AML.


Assuntos
Isotiocianatos/farmacologia , Leucemia Mieloide Aguda/genética , MicroRNAs/efeitos dos fármacos , Adolescente , Adulto , Idoso , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Criança , Pré-Escolar , Progressão da Doença , Feminino , Regulação Leucêmica da Expressão Gênica/genética , Humanos , Leucemia Mieloide Aguda/metabolismo , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Transdução de Sinais , Sulfóxidos
18.
Diabetes Metab Syndr ; 12(6): 863-867, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29748035

RESUMO

BACKGROUND: Subclinical hypothyroidism known as mild thyroid disorder without significant sign and symptoms. The correlation between subclinical hypothyroidism and some of cardiovascular disease risk factors such as serum lipids, homocysteine levels and also insulin resistance index is not well established and the current study was conducted to clarify this issue. METHODS AND MATERIALS: Seventy four patients with mild elevation in levels of thyroid stimulating hormone (TSH) along with normal levels of T3 and T4 were selected as patients group and 74 age and sex matched individuals were selected as healthy control group. Serum insulin, triglyceride, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol and homocysteine levels were measured. Obtained data compared between groups with independent sample t-test. For evaluation of the correlation between mentioned parameters Pearson correlation coefficient method was used. RESULTS: Serum levels of LDL-C and total cholesterol significantly increased in SCH group compared to healthy control group. Homeostatic Model Assessment of Insulin Resistance (HOM-IR) and serum homocysteine level significantly elevated in patients with SCH compared to control group. There was a significant direct correlation between HOM-IR and serum homocysteine levels in SCH patients. CONCLUSION: Subclinical hypothyroidism likely have significant effect on insulin resistance as major diabetes risk factors and also cardiovascular disease risk factors such as homocysteine. The direct correlation between HOM-IR with serum homocysteine level indicate the possible role of insulin resistance in elevation of serum homocysteine in SCH patient group.


Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus/etiologia , Homocisteína/sangue , Hipotireoidismo/sangue , Resistência à Insulina , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Hipotireoidismo/complicações , Masculino , Pessoa de Meia-Idade , Fatores de Risco
19.
Am J Med Sci ; 355(5): 449-455, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29753375

RESUMO

BACKGROUND: Oxidative stress occuring in patients diagnosed with inflammatory bowel disease (IBD), but the relationship between oxidative stress, disease activity and inflammatory markers has not been well established. MATERIALS AND METHODS: A total of 30 patients diagnosed with IBD and 30 volunteers who had normal colonoscopies, selected as controls, were used for this study. The serum levels of antioxidant enzymes (catalase and glutathione peroxidase) and oxidative markers (malondialdehyde [MDA] and total antioxidant capacity) were compared between the 2 groups. Furthermore, their correlations with disease activity scores and inflammatory markers, especially the fecal calprotectin, were examined. RESULTS: Catalase and glutathione peroxidase concentrations were significantly correlated with the level of fecal calprotectin in patients with IBD. Nevertheless, there were no significant correlations between the concentrations of the above-mentioned enzymes and C-reactive protein, erythrocyte sedimentation rate or the activity scores of IBD patients. It should be noted that MDA and total antioxidant capacity levels did not correlate with the inflammatory markers or the disease activity scores. CONCLUSIONS: There was a positive correlation between fecal calprotectin and serum antioxidant enzymes in patients with IBD, but, there was no correlation between antioxidant and oxidative markers in terms of disease activity scores. Hence, the observed significant correlation between the antioxidant enzymes and the fecal calprotectin may be due to either the pro-oxidant potential of calprotectin or its antioxidant role.


Assuntos
Antioxidantes/análise , Catalase/sangue , Fezes/química , Glutationa Peroxidase/sangue , Doenças Inflamatórias Intestinais/diagnóstico , Complexo Antígeno L1 Leucocitário/análise , Adulto , Biomarcadores/análise , Estudos de Casos e Controles , Colonoscopia , Feminino , Humanos , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/enzimologia , Masculino , Índice de Gravidade de Doença
20.
Biomed Res Int ; 2017: 7319504, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29082253

RESUMO

In an attempt to identify herbal drugs which may become useful in the prevention of diabetes, antioxidant potentials and α-amylase inhibition by the ethanol extracts of two plants belonging to Lamiaceae family, Otostegia persica and Zataria multiflora, and their different fractions were studied. Also, inhibition of α-amylase by Salvia mirzayanii and its fractions was evaluated. All of the samples exhibited antioxidant activities, among which ethyl acetate fraction of Zataria multiflora (17.21 ± 0.17 mg GAE/g) was found to contain the highest amounts of phenols and the ethyl acetate fraction of Zataria multiflora (218 ± 2.76 mg QUE/g) had the most values of flavonoids. Ethyl acetate fraction of Zataria multiflora (IC50 = 3.05 ± 0.51 µg/ml) was shown to have the most reducing power and the ethyl acetate fraction of Zataria multiflora (IC50 = 32.17 ± 1.82 µg/ml) exhibited the highest DPPH radical scavenging. The ethyl acetate fraction of Otostegia persica (99.39 ± 0.94%) showed the highest α-amylase inhibitory activity which was similar to acarbose used as a standard. Mode of α-amylase inhibition of the most samples was uncompetitive except for ZMC, OPP, OPC, and SMP which presented competitive inhibition. The present findings showed that studied samples may have some compounds with antioxidant and antidiabetic effects.


Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus/tratamento farmacológico , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Antioxidantes/química , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Lamiaceae/química , Fenóis/química , Extratos Vegetais/química , alfa-Amilases/antagonistas & inibidores
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