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1.
Cell Biochem Funct ; 42(2): e3973, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38488483

RESUMO

The structural and functional disorders of the testis and ovary are one of the main complications of hyperglycemia. Betaine is a trimethyl glycine with antioxidant, antidiabetic, and anti-inflammatory potential. The aim of this study is to investigate the potential of betaine on the expression of aging and oxidative stress markers in ovarian and testicular cells under hyperglycemic conditions. Testicular and ovarian cells were subjected to four different conditions, including normal glucose and hyperglycemia, with or without betaine (5 mM). The cells with hyperglycemia saw an increase in malondialdehyde (MDA), methylglyoxal (MGO), expression of a receptor for AGE, and aging-related genes (ß-GAL), and a decrease in the activity of antioxidant enzymes including catalase, glutathione peroxidase, and superoxide dismutase. The treatment with betaine, in contrast, decreased the amount of MGO and MDA, and also downregulated aging-related signaling. Although hyperglycemia induces senescence in testicular and ovarian cells, the use of betaine may have a protective effect against the cell senescence, which may be useful in the management of infertility.


Assuntos
Antioxidantes , Hiperglicemia , Masculino , Feminino , Humanos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Testículo/metabolismo , Betaína/farmacologia , Betaína/metabolismo , Ovário/metabolismo , Óxido de Magnésio/metabolismo , Estresse Oxidativo , Catalase/metabolismo , Superóxido Dismutase/metabolismo , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , beta-Galactosidase/metabolismo
2.
Int J Neurosci ; 132(9): 917-924, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33175635

RESUMO

AIM OF THE STUDY: In December 2019, a highly pathogenic coronavirus called SARS-CoV-2 (formerly identified as 2019-nCoV) appeared in Wuhan, China, and has since been spreading rapidly around the world. we reviewed the neurological manifestations of this infection and the potential of ACE2 in the nervous system. MATERIALS AND METHODS: Six databases (Medline, Scopus, Embase, Web of Science, WHO, and google scholar) were searched and screened by the authors for having appropriate information about covid-19. Finally, 72 studies were identified, summarized and reviewed. RESULT: The most specific manifestation of SARS-CoV-2 patients is pulmonary distress, and several patients admitted to intensive care units were not able to breathe spontaneously. In addition, the SARS-CoV-2 outbreak has a significant effect on nervous systems and may even lead to serious neurological damage. The neuroinvasive pathobiology is still not fully elucidated and thus the effect of CoV infections on the nervous system needs to be explored. The spike protein of the virus and the angiotensin-converting enzyme 2 (ACE2) lead to the presence of both SARS-CoV and SARS-CoV-2 in the cells and, subsequently, decreased ACE2 expression. CONCLUSION: The therapeutic possibilities of ACE2 antibody, ACE2-derived peptides, and small molecule blockers of ACE2 include a receptor-binding domain blocking approach. Hence, future studies of ACE2 may be very helpful in discovering a therapy for SARS-CoV-2.


Assuntos
COVID-19 , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Enzima de Conversão de Angiotensina 2 , COVID-19/complicações , Humanos , Peptidil Dipeptidase A , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/metabolismo , SARS-CoV-2
3.
Mol Biol Rep ; 48(9): 6423-6433, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34436723

RESUMO

BACKGROUND: Prolonged and excessive salt intake accelerates oxidative stress in kidney tissues, which brings about ER stress. The PERK/ATF4/CHOP/BCL-2 signaling pathway has an essential role in ER stress-induced apoptosis. The present study aimed to investigate the effect of high salt diets on the development of renal fibrosis through CHOP-mediated apoptosis. METHODS AND RESULTS: Twenty-five male Wistar rats were randomly divided into five groups (n = 5 each). Groups 1-5 were treated with 0%, 0.5%, 1%, 1.2%, 1.5% of NaCl dissolved in distilled water, respectively, for 8 weeks. To detect the degree of renal tubular damage, urinary KIM-1 was measured. The slides of renal tissues were stained via Masson's Trichrome staining methods for fibrosis detection. The relative gene expression of ATF4, CHOP, and BCl-2 in renal tissues were analyzed using the qRT-PCR method. The results revealed no significant difference between the urea, creatinine, and urine flow rate of the rats receiving different concentrations of NaCl (groups 2-5) and those of the control group (group 1). The rats treated with 1.5% NaCl (group 5) showed significant elevations in urinary KIM-1 and the mRNA level of CHOP compared to the control group. Mild renal fibrosis was also observed in group 5. CONCLUSIONS: Excessive salt intake leads to fibrosis as it induces the PERK/ATF4/CHOP/BCL-2 signaling pathway in renal tissues. KIM-1 is detectable in urine before the impairment of renal function which can be used as a diagnostic marker to prevent the development of progressive renal failure.


Assuntos
Apoptose/efeitos dos fármacos , Dieta/métodos , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Rim/patologia , Transdução de Sinais/efeitos dos fármacos , Cloreto de Sódio na Dieta/administração & dosagem , Cloreto de Sódio na Dieta/efeitos adversos , Fator de Transcrição CHOP/metabolismo , Animais , Biomarcadores/urina , Moléculas de Adesão Celular/urina , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fibrose , Expressão Gênica/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/genética , Ratos , Ratos Wistar , Fator de Transcrição CHOP/genética
4.
Mol Biol Rep ; 48(7): 5435-5442, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34273031

RESUMO

BACKGROUND: Resveratrol and Quercetin as powerful herbal antioxidant reduce kidney complications of diabetes. The purpose of this study was to evaluate the protective effects of Quercetin and Resveratrol on aging markers in high glucose condition. METHODS AND RESULTS: In this study, HEK-293 cells and kidney tissue of male Wistar rats were used in hyperglycemia condition. Quercetin and Resveratrol for cell culture and in vivo evaluation were used. Amount of methylglyoxal and the gene and protein expression of the Senescence Marker Protein30 (SMP30) were measured using qRT-PCR and ELISA, respectively. High glucose condition in kidney cell and tissue caused increase in glyoxal amount compared to control sample. Treatment with Resveratrol and/or Quercetin significantly decreased the amount of methylglyoxal in a dose-dependent manner. SMP30 expression significantly decreased compare to control group while treatment with Resveratrol and/or Quercetin considerably increased expression level of the protein. Six weeks treatment with Quercetin and Resveratrol had more beneficial effects on aging markers compared with three weeks. CONCLUSIONS: According to the results, it can be concluded that resveratrol and quercetin, as potent herbal antioxidants, may have significant effects in reducing the complications of diabetes in kidneys, as well as preventing the aging of the kidney cells.


Assuntos
Biomarcadores , Glicemia/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Quercetina/farmacologia , Resveratrol/farmacologia , Animais , Antioxidantes/farmacologia , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Hidrolases de Éster Carboxílico/genética , Hidrolases de Éster Carboxílico/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Modelos Animais de Doenças , Glucose/metabolismo , Glucose/farmacologia , Células HEK293 , Humanos , Imuno-Histoquímica , Estresse Oxidativo/efeitos dos fármacos , Aldeído Pirúvico/metabolismo , Ratos
5.
J Physiol Biochem ; 77(2): 205-214, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33555532

RESUMO

Nowadays, the complications related to diabetes, such as nephropathy, cardiovascular problems, and aging, are highly being considered. Renal cell aging is affected by various mechanisms of inflammation, oxidative stress, and basement membrane thickening, which are significant causes of renal dysfunction in diabetes. Due to recent studies, adiponectin plays a key role in diabetes-related kidney diseases as a fat-derived hormone. In diabetes, reduced adiponectin levels are associated to renal cell aging. Oxidative stress and related signaling pathways are the main routes in which adiponectin may be effective to decline diabetes-associated aging. Therefore, adiponectin signaling in target tissues becomes one of the research areas of interest in metabolism and clinical medicine. Studies on adiponectin signaling will increase our understanding of adiponectin role in diabetes-linked diseases as well as shortening life span conditions which may guide the design of antidiabetic and anti-aging drugs.


Assuntos
Adiponectina/genética , Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/genética , Obesidade/tratamento farmacológico , Obesidade/genética , Receptores de Adiponectina/genética , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Adiponectina/metabolismo , Envelhecimento , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Regulação da Expressão Gênica , Humanos , Hipoglicemiantes/uso terapêutico , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Redes e Vias Metabólicas/genética , Obesidade/metabolismo , Obesidade/patologia , Estresse Oxidativo , PPAR alfa/genética , PPAR alfa/metabolismo , Receptores de Adiponectina/metabolismo , Transdução de Sinais
6.
Int J Prev Med ; 11: 184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33456740

RESUMO

BACKGROUND: Oxidative stress and alteration of lipid profile due to obesity and overweight is a major risk factor for atherosclerotic plaque or coronary artery disease. Because of antioxidant and lipid lowering potential of saffron, this study investigated weight alteration, lipid profiles, and insulin resistance index in high-calorie diet rats treated with aqueous extract of saffron stigma and petal. METHODS: Forty Sprague-Dawley male rats were randomly divided into 8 groups including healthy control, high-fat diet control, nicotinic acid treated, Anethum graveolens treated, and saffron stigma and petal treated groups. Rats received a high-calorie diet for 16 weeks. For treatment, aqueous extract of saffron stigma (40 and 80 mg/kg) and petal (50 and 100 mg/kg) was used once daily for 4 weeks. Afterward, lipid profile, oxidative stress status, and insulin and adiponectin levels were measured using desired kits. RESULTS: There was a significant decrease in the mean weight of the groups receiving saffron stigma and petal compared to control group (P < 0.05). The increased level of insulin hormone in obese group was improved in treated groups especially in the case of saffron stigma. Also, the decreased level of adiponectin was recovered in treated groups. An improvement was seen in oxidative stress markers and lipid profiles in treated groups compared to obesity pair. CONCLUSIONS: In this study, a remarkable antioxidant and lipid lowering potential was detected for saffron stigma, which could improve insulin resistance in obese rats. Therapeutic and protective effect of saffron is mainly related to its richness in phenolic compounds. Saffron stigma compared with petal had more notable effect, which could and should be mentioned in pharmaceutical studies.

7.
Res Pharm Sci ; 14(3): 255-262, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31160903

RESUMO

Oxidative stress plays a crucial role in the pathogenesis of hyperglycemia mediated complications. Since a great number of researches have reported antioxidant features of saffron, this study investigated the antioxidant effect of saffron stigma extract (SSE) in streptozotocin-induced diabetic rats. Twenty eight diabetic male Wistar rats were divided in four groups containing: two diabetic groups receiving 25 and 100 mg/kg SSE respectively, one diabetic group receiving glibenclamide (0.6 mg/kg) and one diabetic control group receiving normal saline. Seven healthy adult male Wistar rats were also used as normal control group. After treatment (21 days), fasting blood glucose, insulin, oxidative stress markers, and pancreatic regeneration were assessed. The gene expression level of heat shock factor1, heat shock protein 27, and heat shock protein 70, also glucokinase (GK), and glucose 6-phosphatase (G6Pase) were determined using real-time polymerase chain reaction (RT-PCR). SSE in high dose (100 mg/kg) reduced fasting blood glucose (8.3 ± 0.4 mmol/L) compared with diabetic control (24.6 ± 1.2 mmol/L) (P < 0.05). Furthermore, SSE in high dose increased insulin level compared with diabetic control group (12.7 ± 0.6 vs 7.1 ± 0.3 µU/mL). RT-PCR analysis revealed decline in mRNA levels of stress proteins and G6Pase and increase in mRNA level of GK in treatment diabetic groups compared with diabetic control group. Data showed antioxidant and antidiabetic effects of SSE through altering insulin release and glucose metabolism pathways. Hypoglycemic potential of SSE may be due to change in GK and G6Pase enzymes expression. These findings provide a basis for the therapeutic potential of saffron in treatment of diabetes.

8.
Cell Biochem Funct ; 37(3): 148-152, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30908696

RESUMO

Adiponectin (APN) is an adipocytokine, secreted from adipose tissue and has anti-inflammatory, anti-ageing, and antidiabetic properties. Hyperglycaemia can damage the renal cells, and mammalian target of rapamycin (mTOR), along with Sirtuin 1 (SIRT1), have an important role in kidney cell response to hyperglycaemia. Therefore, understanding the relationship between adiponectin, mTOR, and SIRT1 proteins is beneficial for deciphering the mechanism of adiponectin function. In this study, Human Embryonic Kidney-293 (HEK-293) cells were cultured under normal and high-glucose condition, with and without APN (1, 10, and 100 ng/mL) for 48 hours. mTOR protein expression was evaluated by western blot analysis, and SIRT1 protein was assessed using ELISA method. To evaluate hyperglycaemia-mediated cytotoxicity, cell viability was determined using MTT assay. Data showed that APN in high dose (100 ng/mL) significantly reduced the expression of mTOR and p-mTOR, increased SIRT1 protein, and also improved cell viability compared with the control high glucose (p ≤ 0.05). According to this results, APN can be useful in preventing renal cell damage, by affecting on the expression of mTOR and SIRT1 proteins, as well as increasing the survival of kidney cells in hyperglycaemia conditions. SIGNIFICANCE OF THE STUDY: Adiponectin triggered mTOR/p-mTOR/SIRT1 pathway and decreased cell death in human kidney cells. Our findings provide preliminary experimental data that support further studies on the potential therapeutic role of adiponectin in diabetes and diabetic-induced metabolic complications.


Assuntos
Adiponectina/farmacologia , Adiponectina/uso terapêutico , Hiperglicemia/complicações , Nefropatias/tratamento farmacológico , Nefropatias/prevenção & controle , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Células HEK293 , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/patologia , Hiperglicemia/prevenção & controle , Nefropatias/patologia , Sirtuína 1/análise , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/metabolismo , Serina-Treonina Quinases TOR/análise , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo
9.
Clin Med Insights Cardiol ; 12: 1179546818759286, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29497341

RESUMO

Introduction: The alteration in serum lipid profile; increase in total cholesterol (TC), triacylglycerol (TAG), and low-density lipoprotein cholesterol (LDL-C); and reduction in high-density lipoprotein cholesterol (HDL-C) are key factors in cardiovascular disease progression. The high prevalence and severity of cardiovascular diseases require new screening tools for better evaluation. Atherogenic index (AI) (LDL-C/HDL-C) and coronary risk index (CRI) (TC/HDL-C) can be strong markers for predicting the risk of atherosclerosis and coronary heart disease and disclose the presence of LDL or TAG in the serum of related patients. To implement this strategy, the AIs and CRIs in our population were assessed. In this study, a total of 5207 subjects were recruited and AIs and CRIs were calculated for all of them. According to our data, age, body mass index, sex, as well as CRI and AI had affirmative correlation with TC, LDL-C, TAG, systolic blood pressure, and diastolic blood pressure. By increasing these factors, AIs and CRIs were augmented. Moreover, in situations where all atherogenic parameters are normal, these parameters may be the alternative screening tool.

10.
J Complement Integr Med ; 15(2)2017 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-29068789

RESUMO

Background Prevention and treatment of obesity is a way to reduce cardiovascular disease, diabetes and depression. Pumpkin as a favorable plant has different properties notably antioxidant, lipid-lowering and anti-diabetic potential. The aim of this study was to assess the anti-obesity effects of pumpkin in diet-induced obese rats. Methods Thirty adult male Wistar rats were randomly divided into five groups (n=6) of healthy control, dietary fatty control rats, and three experimental dietary fatty rats that received hydro-alcoholic extract of pumpkin once daily at doses 100 and 200 and 400 mg/kg, respectively. At the end of 6 weeks, lipid profile, atherogenicity, liver enzymes, and oxidative stress status were measured. Results Pumpkin in a dose-dependent manner dramatically decreased triglycerides and low-density lipoprotein, and liver enzymes while high-density lipoprotein was markedly increased in treated groups. Pumpkin also increased glutathione level in comparison with obese control group. Conclusions Pumpkin ameliorated oxidative stress and dyslipidemia in obese rats, leading to decrease cardiovascular disease risk in obesity.


Assuntos
HDL-Colesterol/sangue , Cucurbita , Dieta Hiperlipídica , Resistência à Insulina , Obesidade/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Aterosclerose/sangue , Aterosclerose/prevenção & controle , Gorduras na Dieta/efeitos adversos , Dislipidemias/sangue , Dislipidemias/etiologia , Dislipidemias/prevenção & controle , Glutationa/sangue , Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Obesidade/complicações , Obesidade/tratamento farmacológico , Fitoterapia , Extratos Vegetais/metabolismo , Extratos Vegetais/uso terapêutico , Ratos Wistar
11.
Vet Parasitol ; 245: 78-85, 2017 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-28969842

RESUMO

Little is known about the genotypes of Echinococcus spp. and their life cycles in eastern Iran. We analysed the partial sequences of the nad1 and cox1 genes from 17 isolates from hydatid cyst-infected patients (n=9), camels (n=5) and sheep (n=3) in Birjand, eastern Iran. A new primer pair was also used to amplify the long fragment (1180bp) of the cox1 gene. All camel and eight human isolates were G6 strains of Echinococcus canadensis while one human isolate and the three sheep isolates were G1 genotypes (sheep strain) of E. granulosus sensu stricto (s.s.). Nad1 and cox1 sequence analyses showed high G6 genetic homogeneity, similar to previously reported G6 strains from southeast and central Iran, Sudan and Mauritania. Low nucleotide and haplotype diversity similar to G6 strains from Russia (Altai republic) and Kazakhstan was also found, consistent with a bottleneck effect. In this study, G6 was the most common Echinococcus genotype. Genetic homogeneity of east, southeast and central Iranian G6 and its low genetic diversity may be due limited mobility and contact between humans and camels from other regions because of large, inhospitable deserts.


Assuntos
Camelus/parasitologia , Equinococose/veterinária , Echinococcus/classificação , Echinococcus/genética , Genótipo , Animais , DNA de Helmintos/genética , Equinococose/epidemiologia , Equinococose/parasitologia , Humanos , Irã (Geográfico)/epidemiologia , Filogenia , Reação em Cadeia da Polimerase
12.
Int J Prev Med ; 8: 64, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28966753

RESUMO

BACKGROUND: Hyperglycemia-mediated oxidative stress implicates in etiology of kidney cell aging and diabetic nephropathy. We evaluated the effects of different doses of resveratrol and quercetin and their combination therapy on aging marker in human kidney cell culture under hyperglycemia condition. METHODS: Human embryonic kidney cell (HEK-293) was cultured in Dulbecco's Modified Eagle Medium (DMEM) containing 100 mM (18 mg/L) for 24 h. The cells were treated with resveratrol (2.5, 5, 10 µm), quercetin (3, 6, 12 µm), and combination of these (R 2.5 µm, Q 3 µm) and (R 5 µm, Q 6 µm) and (R 10 µm, Q 12 µm) for 48 h, and then, cells were lysed to access RNA and lysate. RESULTS: The analysis of data showed that beta-galactosidase enzyme gene expression as an aging marker in all treatment groups has reduced in a dose-dependent manner. Gene expression of Sirtuin1 and thioredoxin (Trx) in all treated groups in comparison to control group increased in a dose-dependent fashion. Trx interacting protein (TXNIP) gene expression decreased in a dose-dependent manner in all treated groups, especially in resveratrol and combination therapy. CONCLUSIONS: According to the results of this research, quercetin, resveratrol, and especially combination treatments with increased expression levels of antioxidants, can reduce aging markers in HEK cell line in hyperglycemia conditions. These results lead us to use flavonoids such as resveratrol for anti-aging potential.

13.
Iran J Med Sci ; 42(3): 275-283, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28533576

RESUMO

BACKGROUND: Discriminating latent tuberculosis infection (LTBI) from active TBI may be challenging. The objective of this study was to produce the recombinant L-alanine dehydrogenase (AlaDH) antigen and evaluate individuals with LTBI, those with active TBI, and uninfected individuals by enzyme-linked immunospot assay (ELISPOT) in order to distinguish LTBI from active TBI. METHODS: This exploratory study was performed in the Iranian city of Shiraz from 2014 to 2015. The study population (N=99) was divided into 3 groups: individuals with newly diagnosed active TBI (n=33), their household contacts (n=33), and controls (n=33). AlaDH was produced through PCR and cloning methods. The diagnostic characteristics of AlaDH vs. ESAT-6/CFP-10 were evaluated in responses to interferon-γ (IFN-γ) and interleukin-2 (IL-2) with ELISPOT. Differences between the groups were assessed with the Kruskal-Wallis and Mann-Whitney tests for nonparametric data analysis. The statistical analyses were performed with SPSS, version 16. RESULTS: IFN-γ responses to both ESAT-6/CFP-10 (P=0.81) and AlaDH (P=0.18) revealed that there were no significant differences between the individuals with LTBI and those with active TBI. The same results were determined for IL-2 responses to ESAT-6/CFP-10 between the 2 groups, while significantly higher IL-2 responses to AlaDH were observed in LTBI than in active TBI. According to the ROC curve analysis, a cutoff value of 275 SFC showed sensitivity of 75.8% and specificity of 78.8% for distinguishing LTBI from active TBI by IL-2 responses to AlaDH. CONCLUSION: The current study suggests that it may be possible to discriminate LTBI from active TBI by IL-2 responses to AlaDH.

14.
Iran J Med Sci ; 41(4): 296-304, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27365551

RESUMO

BACKGROUND: Macrophage immune responses are affected by the secretory proteins of Mycobacterium tuberculosis (Mtb). This study aimed to examine the immune responses of macrophages to Mtb secretory antigens, namely ESAT-6, CFP-10, and ESAT-6/CFP-10. METHODS: THP-1 cells (a human monocytic cell line) were cultured and differentiated to macrophages by phorbol 12-myristate 13-acetate. The cytotoxicity of the recombinant Mtb proteins was assessed using the MTT assay. Two important immune responses of macrophages, namely NO and ROS production, were measured in response to the ESAT-6, CFP-10, and ESAT-6/CFP-10 antigens. The data were analyzed using one-way ANOVA with SPSS, version 16, and considered significant at P<0.05. RESULTS: The results showed that the ESAT-6, CFP-10, and ESAT-6/CFP-10 proteins markedly reduced macrophage immune response. The treatment of the THP-1-differentiated cells with ESAT-6, CFP-10, and ESAT-6/CFP-10 reduced NO and ROS production. The treated THP-1-differentiated cells exhibited less inducible NO synthase activity than did the untreated cells. No toxic effect on macrophage viability was observed for the applied proteins at the different concentrations. CONCLUSION: It seems that the decline in macrophage immune response is due to the suppression of NO and ROS production pathways without any effect on cell viability.

15.
Acta Trop ; 158: 68-76, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26899681

RESUMO

Iran has been identified being among the countries with the highest number of cutaneous leishmaniasis (CL) cases. South Khorasan province in East Iran is an emerging focus of CL. Species identification of sixty clinical samples by ITS1 PCR-RFLP presented evidence for the dominance of Leishmania tropica (90%) in this region. Analysis of the ITS1 sequence of 19 L. tropica isolates revealed seven closely related sequence types. In addition, ITS1 sequences available in GenBank from other Iranian regions were compiled for comparison with the studied isolates. Iranian L. tropica was distributed in two main clusters. All East Iranian sequence types were grouped with strains from foci from Southeast and Central regions in cluster A, showing highly similar sequences. The highest similarity was observed between most L. tropica from East and all isolates from Southeast regions and from Savojbolagh county in Central Iran. Southwest L. tropica was shown to be paraphyletic as the isolates were distributed in both clusters A and B. All Northeastern L. tropica were part of cluster B, however they showed significant heterogeneity and were distributed in different subclusters. Distribution of L. tropica populations was to some extent congruent with genetic lineages of Phlebotomus sergenti in Iran and may be an evidence for parasite-vector co-evolution. Southeast-East L. tropica was also similar to strains from Herat province in Afghanistan at the East border of Iran. This is the first comprehensive study on population structure of L. tropica in Iran that provides a guideline for appropriate sampling for further molecular based epidemiological studies.


Assuntos
Leishmania tropica/classificação , Leishmania tropica/genética , Leishmaniose Cutânea/epidemiologia , Phlebotomus/parasitologia , Filogenia , Animais , Doenças Endêmicas , Humanos , Irã (Geográfico)/epidemiologia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNA
16.
J Microbiol Immunol Infect ; 49(2): 249-56, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25081983

RESUMO

BACKGROUND/PURPOSE: Tuberculous granulomas are the sites of interaction between the T cells, macrophages, and extracellular matrix (ECM) to control the infection caused by Mycobacterium tuberculosis (M. tuberculosis). A predominant role of RD-1-encoded secretory proteins, early secreted antigenic target-6 (ESAT-6), and culture filtrate protein-10 (CFP-10) in the formation of granulomas has recently been emphasized. However, the precise molecular events that induce the formation of these granulomatous structures are yet to be elucidated. Macrophages use integrins to adhere to fibronectin (FN) as a major component of the ECM. The major goal of this study was to investigate whether recombinant M. tuberculosis antigens can modulate integrin-mediated macrophage adhesion. METHODS: Differentiated THP-1 cell line was stimulated with recombinant ESAT-6, CFP-10, and ESAT-6/CFP-10 proteins and evaluated for alterations in the expression levels of α5ß1 and α4ß1 by semiquantitative real-time polymerase chain reaction. The role of these recombinant antigens in the cytoskeleton rearrangement was determined by adhesion assay and immunofluorescent microscopy. RESULTS: Our data showed that ESAT-6 and ESAT-6/CFP-10 fusion proteins could induce adhesion of macrophages to FN through α4ß1 integrin. An increased expression level of α4ß1 integrin in comparison with α5ß1 integrin in differentiated THP-1 cells was also observed. Results of immunofluorescence studies showed that recombinant proteins-treated THP-1 cells form well-organized stress fibers and focal contacts containing vinculin compared with untreated THP-1 cells. CONCLUSION: Increased expression level of α4ß1 in differentiated THP-1 cells could suggest the important role of α4ß1 integrin in adhesion and focal contact formation of macrophages exposed to M. tuberculosis antigens.


Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Fibronectinas/metabolismo , Interações Hospedeiro-Patógeno , Macrófagos/metabolismo , Mycobacterium tuberculosis/fisiologia , Receptores de Fibronectina/análise , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Linhagem Celular , Perfilação da Expressão Gênica , Humanos , Integrina alfa4beta1/análise , Integrina alfa4beta1/genética , Integrina alfa5beta1/análise , Integrina alfa5beta1/genética , Mycobacterium tuberculosis/genética , Ligação Proteica , Receptores de Fibronectina/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
17.
Pak J Pharm Sci ; 28(6): 2095-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26639503

RESUMO

One of the most common disorders of the endocrine system is diabetes mellitus. This disease is associated with dyslipidemia. Adiponectin is a protein hormone that secreted by adipocytes and has an important role in regulating of glucose and fatty acid metabolic pathways. This study was designed to investigate the changes in serum level of adiponectin in diabetic rats treated with hydroalcoholic extracts of three medicinal plants; jujube (Ziziphus jujuba), barberry (Berberis vulgaris) and saffron (Crocus sativus) in comparison with quercetin. Streptozotocin -induced diabetic male rats were gavaged with specified doses of the extracts (25 and 100mg/kg) for two weeks. At the end of treatment period, fasting blood specimens were collected. The levels of adiponectin, fasting blood sugar (FBS), total Cholesterol, triglycerides, HDL-C and LDL-C were measured. Statistical analysis showed that serum levels of triglyceride and VLDL decreased significantly (P<0.05) in all treated groups. FBS level in all treated groups, decreased significantly and reach to normoglycemic level (P<0.05). Except Jujube, other plant extracts had no effect on cholesterol. Jujube in two doses (25 and 100mg/kg) could increased significantly HDL-C (P<0.05) with no effect on total cholesterol and LDL-C. Serum adiponectin level increased in all treated groups. These beneficial effects of C. sativus, B. vulgaris and Z. jujube extracts and quercetin in diabetic rats may be associated with increase in adiponectin level.


Assuntos
Adiponectina/sangue , Berberis , Glicemia/efeitos dos fármacos , Crocus , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Ziziphus , Animais , Berberis/química , Biomarcadores/sangue , Glicemia/metabolismo , Crocus/química , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/diagnóstico , Hipoglicemiantes/isolamento & purificação , Irã (Geográfico) , Lipídeos/sangue , Masculino , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Quercetina/farmacologia , Ratos Sprague-Dawley , Ziziphus/química
18.
EXCLI J ; 14: 908-15, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26600752

RESUMO

Atherogenic dyslipidemia, characterized by an increased level of lipoprotein (a) and a decreased level of adiponectin, is a major risk factor for cardiovascular diseases in diabetic patients. To reduce cardiovascular risk in diabetic patients, use of agents with antidiabetic and anti-atherogenic potential is required. Using an animal model of diabetes, we investigated the antiatherogenic potential of extracts of three medicinal plants: jujube, barberry, and saffron. For this, serum level of fasting blood glucose, lipid profile, malondialdehyde, total antioxidant capacity, adiponectin and lipoprotein (a) in diabetic control and extract treated groups were measured. Statistical analysis of measurements showed that serum levels of fasting blood glucose, triglyceride, and VLDL decreased significantly (P < 0.05) in all treated groups. Treatment with all extracts reduced lipid peroxidation and increased antioxidant capacity of the experimental diabetic groups. Serum adiponectin levels increased in all treated groups, whereas lipoprotein (a) levels decreased, most markedly when treated with jujube extract. Jujube, saffron, and barberry extracts are beneficial in ameliorating oxidative stress and atherogenic risk of diabetic rats. This highlights the benefits of further investigating the cardio-protective potential of medicinal plant extracts and evaluating their usefulness as cardio protective agents in clinical practice.

19.
Comp Biochem Physiol C Toxicol Pharmacol ; 135C(3): 357-64, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12927910

RESUMO

Effects of the intraperitoneal injection of quercetin in streptozocin-induced diabetic and normal rats were investigated and compared. Although quercetin had no effect on plasma glucose level of normal animals, it significantly and dose-dependently decreased the plasma glucose level of streptozocin-induced diabetic rats. Glucose tolerance tests of the diabetic animals approached those of normal rats, their plasma cholesterol and triglycerides were reduced significantly, while their hepatic glucokinase activity was significantly increased upon quercetin treatment. In normal rats, quercetin did not affect the glucose tolerance test, but resulted in an increase of plasma cholesterol and triglycerides and a decrease in hepatic glucokinase activity. No significant pathologic changes were noted in hepatocytes or kidney tubules and glomeruli, while the number of pancreatic islets significantly increased in both treated normal and diabetic groups. It is concluded that quercetin, a flavonoid with antioxidant properties brings about the regeneration of the pancreatic islets and probably increases insulin release in streptozocin-induced diabetic rats; thus exerting its beneficial antidiabetic effects. However, it may be of little value in normoglycemic animals.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Quercetina/uso terapêutico , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Hipoglicemiantes/farmacologia , Masculino , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Quercetina/farmacologia , Ratos , Ratos Sprague-Dawley
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