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1.
Biol Trace Elem Res ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39004669

RESUMO

MDMA can cause serious adverse effects on vital organs such as the heart, brain, and liver. Additionally, MDMA consumption can also potentially cause various endocrine system dysfunctions. The previous study has shown that pre-treatment of zinc can reduce the cytotoxicity of MDMA on the Leydig cell line (TM3). In this study, we investigated the mechanisms involved in the treatment with MDMA on the apoptosis of TM3 cells and the effects of zinc pre-treatment on reducing the apoptotic effects of MDMA. TM3 cells were incubated with MDMA (5 mM), zinc (8 µM), and zinc (8 µM) prior to MDMA (5 mM) for 48 h. The cells were pre-treated with zinc for 24 h prior to the administration of MDMA, and the total culture time was 48h. The effect of different treatment groups in causing oxidative stress and apoptosis in TM3 cells was measured by DCF, TUNNEL, and western blot tests, respectively. Our results revealed that the number of DCF and tunnel-positive cells increases as a result of MDMA treatment. In addition, the treatment with MDMA increased the expression of pro-apoptotic proteins caspase 3, Bax, and p53. Conversely, the expression of anti-apoptotic protein Bcl-2 decreased. Zinc pre-treatment significantly decreased the expression of pro-apoptotic proteins and the number of tunnels and DCF-positive cells compared to the MDMA-only group. It is concluded that MDMA has a toxic effect and causes apoptosis on TM3 cells, and also, pre-treatment with zinc mitigates the ROS production and toxic effect of MDMA and MDMA-induced apoptosis in TM3 cells.

2.
Int J Dev Neurosci ; 84(2): 109-121, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38311365

RESUMO

The mother's thyroid hormone status during gestation and the first few months after delivery can play a crucial role in maturation during the brain development of the child. Transient abnormalities in thyroid function at birth indicate developmental and cognitive disorders in adulthood. Choline supplementation during gestation and the perinatal period in rats causes long-lasting memory improvement in the offspring. However, it remains unclear whether choline is able to restore the deficits in rats with maternal hypothyroidism. The aim of this study was to evaluate the effects of choline supplementation on the alteration of cognitive-behavioral function, long-term potentiation (LTP), and morphological changes as well as apoptosis in pre-pubertal offspring rats. To induce hypothyroidism, 6-propyl-2-thiouracil was added to the drinking water from the 6th day of gestation to the 21st postnatal day (PND). Choline treatment was started twice a day on the first day of the gestation until PND 21 via gavage. LTP recording and Morris water maze (MWM) test were conducted at PND 28. Then, the rats were sacrificed to assess their brains. The results revealed that developmental thyroid hormone deficiency impaired spatial learning and memory and reduced LTP (both: P < 0.001). Choline treatment alleviated LTP (P < 0.001), as well as learning and memory deficits (P < 0.01) in both male and female hypothyroid rats. However, no significant changes were observed in the number of caspase-3 stained cells in choline-receiving hypothyroid groups. The results revealed that developmental thyroid hormone deficiency impaired spatial learning and memory and reduced LTP. Choline treatment alleviated LTP, as well as learning and memory deficits in both male and female hypothyroid rats.


Assuntos
Hipotireoidismo , Potenciação de Longa Duração , Humanos , Gravidez , Criança , Ratos , Animais , Masculino , Feminino , Mães , Hipotireoidismo/complicações , Hipotireoidismo/tratamento farmacológico , Hormônios Tireóideos/farmacologia , Hipocampo , Transtornos da Memória/etiologia , Cognição , Apoptose , Colina/uso terapêutico , Colina/farmacologia , Suplementos Nutricionais , Aprendizagem em Labirinto
3.
Maedica (Bucur) ; 18(3): 442-446, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38023762

RESUMO

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known as a positivesense single-strand RNA virus and leads to Coronavirus disease 2019 (COVID-19). Coronaviruses significantly impact the human respiratory tract. Coronavirus disease is potentially fatal and transmissible in the world. In this study we evaluated the presence or absence of SARS-CoV-2 in 220 patients with un-explained pneumonia by TaqMan real-time PCR assay regarding open reading frame (ORF1ab) and nucleocapsid (N) protein genes. Materials and methods: Totally, 224 patients entered the study. Upper and lower respiratory tract secretion samples were obtained during 2020 from patients. Samples contained nose and throat swabs with viral transport medium. RNA was isolated from clinical samples with the GenePure Plus fully automatic Nucleic Acid Purification System, NPA-32+ (Hangzhou Bioer Technology Co. Ltd, Hangzhou, China). Outcomes: 72.32% of cases were positive for COVID-19. All positive cases had the most common symptoms of illness regarding fatigue, dry cough, dyspnea, headache, abdominal pain, nausa, vomiting and myalgia. Fever was observed in 50% of positive cases. Chest computed tomography (CT) scan of all tested patients indicated two-sided chest involvement. Conclusion:Detection of COVID-19 by TaqMan real-time PCR seems to be a powerful method for the screening and detection of novel corona virus infection.

4.
Mol Biol Rep ; 50(3): 2351-2356, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36577834

RESUMO

BACKGROUND: Thyroid hormones play a vital function in the maturation in the course of mind development. Regarding the well-known effects of choline on brain-derived neurotrophic factor (BDNF), the study examined the effects of choline on hippocampal BDNF gene expression in maternal hypothyroidism rats. METHODS AND RESULTS: To induce the hypothyroidism, 6-propyl-2-thiouracil was introduced to the ingesting water from the sixth day of gestation to twenty-first postnatal day (PND). Choline-treatment started twice a day on the first day of gestation until PND 21. On PND28, pups were sacrificed. The expression of BDNF gene was evaluated after the hippocampus was harvested. Our results demonstrated that both male and female pre-pubertal offspring rats' BDNF gene expression was decreased by developmental hypothyroidism. Choline increases the ratio of relative gene expression of BDNF in the hippocampus of males and females in the control/hypothyroidism group, especially in males. CONCLUSIONS: It can be concluded that maternal choline supplementation on the first day of gestation until PND 21 improves brain development and cognitive function in pre-pubertal offspring rats regarding control/hypothyroidism groups.


Assuntos
Hipotireoidismo , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Masculino , Ratos , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Colina/farmacologia , Colina/metabolismo , Suplementos Nutricionais , Expressão Gênica , Hipocampo/metabolismo , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/genética , Hipotireoidismo/metabolismo , Mães , Efeitos Tardios da Exposição Pré-Natal/metabolismo
5.
ARYA Atheroscler ; 19(1): 12-16, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38883156

RESUMO

BACKGROUND: The purpose of this study was to identify the angiotensin-converting enzyme (ACE) gene (I/D) variations in CAD patients and healthy controls in an Iranian population (West Azerbaijan province of Iran). METHOD: This cross-sectional study included 95 CAD patients and 203 healthy controls. ACE I/D polymorphisms were assessed using PCR, and their frequency was determined. RESULTS: There were 298 people, 95 CAD patients, and 203 controls, with an average age of 50.96±3.45 and 51.14±10.20. We discovered that the frequency of the D allele was significantly higher in CAD patients than in controls (P = 0.0009). In contrast, the frequency of the I allele was significantly higher in controls than in CAD patients (P = 0.0009). The D allele carriers genotypes (DD + ID) were more frequent in the CAD patients than in the control group (P = 0.008). The ACE II genotype-state carriers were more common in the control group than in CAD patients (P = 0.008). However, in the case of the ACE ID genotype, no significant differences were not found in the tested groups (P = 0.47). CONCLUSIONS: These findings suggest that individuals with the ACE DD genotype are predisposed to CAD, whereas individuals with the ACE II genotype state are protected.

6.
Bratisl Lek Listy ; 123(10): 736-739, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35913009

RESUMO

OBJECTIVES: Present study has been carried out to analyze the IL-17R gene expression in PBMCs of patients with premature coronary artery disease (CAD) in comparison to normal controls. BACKGROUND: Premature CAD results in disability and lack of quality of life over the years and consequent mortality. Cardiovascular disease (CVD) has global distribution. In 2022, CAD is the leading cause of mortality in the United States and Iran. IL-17 cytokine family plays an important role in promoting inflammation and producing pro-inflammatory cytokines, chemokines, and matrix metalloproteinases. METHODS: Entirely, 60 subjects were entered into this examination. The case group consisted of 30 subjects with CAD as well as the control group which consisted of 30 healthy persons. The real-time quantitative reverse transcription PCR assay was used to find out, the relative expression (fold) level of IL-17R gene. RESULTS: Our findings indicated that, the relative expression (fold) level of IL-17R gene in the patients group showed an increased level as compared to the control group. The analysis of findingsobtained in this study showed that the patient group is significantly different from the control group regarding the IL-17R mRNA level (fold) (p = 0.035). CONCLUSION: It has been concluded that IL-17R plays an important role in the pathogenesis of CAD. It follows that superior understanding of IL-17/IL-17R signaling way will be vital for innovating novel therapeutic targets that will facilitate the designing of new drugs for the management of patients (Ref. 40).


Assuntos
Doença da Artéria Coronariana , Receptores de Interleucina-17 , Doença da Artéria Coronariana/genética , Citocinas/genética , Expressão Gênica , Humanos , Interleucina-17/genética , Interleucina-17/metabolismo , Qualidade de Vida , Receptores de Interleucina-17/genética , Receptores de Interleucina-17/metabolismo
7.
Cell Mol Biol (Noisy-le-grand) ; 68(4): 158-169, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35988277

RESUMO

This study examined the effect of melatonin on oxidative stress, expression of pro-apoptotic protein, anti-apoptotic proteins, and the activity of the PI3K/Akt signaling pathway in the human ovarian cancer cell line (OVCAR3). OVCAR3 cells were treated with cisplatin, melatonin, cisplatin + melatonin, and siRNA Akt. Reactive oxygen species levels were assessed. The expression of the proteins was determined by Western blot. Melatonin administration significantly increased intracellular ROS generation, the cleavage of caspase 3 and decreased phosphorylation of Akt. Combination therapy of cisplatin and melatonin increases apoptosis in the OVCAR-3 cells by inhibiting of PI3K/Akt signaling pathway and exacerbating oxidative stress.


Assuntos
Melatonina , Neoplasias Ovarianas , Apoptose , Linhagem Celular Tumoral , Cisplatino/farmacologia , Feminino , Humanos , Melatonina/farmacologia , Neoplasias Ovarianas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo
8.
Rep Biochem Mol Biol ; 10(4): 675-685, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35291604

RESUMO

Background: This study evaluates the effect of simultaneous AKT inhibition and cisplatin therapy in changes of Reactive Oxygen Species (ROS) production, apoptosis induction, and cell survival in cisplatin-resistant OVCAR3 cell. Methods: OVCAR3 cancer cells were treated with cisplatin, Ly 294002 (LY), and cisplatin+Ly to investigate the cytotoxicity effect of the mentioned groups via MTT assay. Then, DCFH-DA (2', 7'-dichlorodihydro fluorescein diacetate) assay kit is used to assess the potential of treated groups in intracellular ROS generation. Protein expression levels of caspase-3, cleaved caspase 3, PI3K, Akt, p-Akt, XIAP, and Survivin are estimated through immunoblotting assay in all three experimental groups. Results: The results showed that all three treated groups, including cisplatin and Ly alone and co-administration of cisplatin+Ly, could reduce the cell vitality of OVCAR3 cancer cells, induced intracellular production of ROS and increased the expression level of activated caspase 3 and Akt protein, whereas down-regulated the phosphorylation of Akt protein. However, the effect of combination therapy was more tangible compared to single therapy and control groups. In contrast, the expression amount of XIAP, Survivin, and PI3K did not show detectable changes in comparison with the control group. Conclusion: The results showed that the AKT inhibition by Ly could sensitize the OVCAR3 cancer cells to the cisplatin and lower the effective dose of cisplatin through hyperactivation of oxidative stress.

9.
Int J Reprod Biomed ; 18(9): 777-784, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33062923

RESUMO

BACKGROUND: 3, 4-Methylenedioxymethamphetamine (MDMA) is commonly known as the most famous amphetamine derivative. OBJECTIVE: To evaluate the influence of zinc on MDMA-induced apoptosis and caspase- 3 gene expression in Leydig cell line (TM3). MATERIALS AND METHODS: Leydig cells were studied in differenet treatment groups regarding MDMA (0, 0.5, 1, 3, 5 mM) and zinc (0, 4, 8, 16, 32 µM). By the way, the effective concentration was determined to be 5 mM for MDMA and 8 µM for zinc. Then, TM3 cells were cultured in free medium as control (group I), medium containing MDMA (5 mM) (group II), zinc (8 µM) (group III), and zinc (8 µM) prior to MDMA (5 mM) (group IV) as well as in an untreated group (control). Cell viability was assessed at different times after cell culture by MTT assay. The mRNA expression level of caspase-3 was analyzed using real-time quantitative polymerase chain reaction. RESULTS: The cellular viability was significantly reduced in TM3 cells after 24 hr and 48 hr exposure time regarding different concentrations of MDMA as well as high concentration of zinc (16 and 32 µM). Cell viability was increased in the group that received zinc (8 µM) before addition of MDMA (5 mM) compared to the control and MDMA groups. The mean ± SE of fold was 22.40 ± 7.5, 0.06 ± 0.02, and 0.009 ± 0.003 in MDMA, zinc, and zinc + MDMA groups, respectively. The mean of caspase-3 mRNA level was significantly increased in the MDMA-treated group (5 mM), while the relative expression of caspase-3 gene was significantly decreased in the zinc (8 µM) + MDMA (5 mM) group compared with the MDMA (5 mM) group (p = 0.001). CONCLUSION: Dietary intake of zinc has a protective effect against MDMA consumption in mouse.

10.
Int J Fertil Steril ; 14(3): 223-227, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33098390

RESUMO

BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA) disrupts function of the endocrine system and different organs such as heart, blood vessels, kidney, liver and nervous systems. This revision was conducted to evaluate impact of MDMA on apoptosis and Zinc in the MDMA-induced apoptosis of cultured Sertoli cells by measuring Caspase-3 gene expression. MATERIALS AND METHODS: In this experimental study, Sertoli cells were incubated with MDMA (0, 0.5, 1, 3 and 5 mM), Zinc (0, 8, 16, 32, 64 µM) and Zinc (8 µM) prior to adding MDMA (5 mM) for 24 and 48 hours. MTT assay was used for evaluating impacts of these conditions on the viability of Sertoli cells. Caspase-3 gene expression level was detected using quantitative reverse transcription PCR (qRT-PCR) in all of the tested groups. RESULTS: Finding showed that cellular viability was decreased and level of Caspase-3 mRNA was increased in MDMA treated cells. Additionally, pre-treatment with Zinc (8 µM) attenuated MDMA-induced apoptosis and down-regulated caspase-3. The mean of caspase-3 mRNA level (fold change ± SE) was 3.98 ± 1.18, 0.31 ± 0.28, and 1.72 ± 0.28 in respectively MDMA (5 mM), Zinc (8 µM), and Zinc+MDMA groups vs. control group. The mean of Caspase-3 mRNA (fold change) was not statistically different in the tested groups (P>0.05), unless MDMA (5 mM) group (P=0.008). CONCLUSION: We suggest that MDMA toxicity could be involved in apoptosis of Sertoli cells. In addition, Zinc could reduce MDMA-induced apoptosis by down-regulation of Caspase-3 mRNA levels.

11.
Iran J Kidney Dis ; 14(5): 389-398, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32943594

RESUMO

INTRODUCTION: Seven months after the emergence of SARS-COV-2 virus, there is paucity of data regarding the epidemiology of the virus in hemodialysis patients. We aim to present the results of the screening program implied after outbreak of COVID-19 in a referral hemodialysis ward. METHODS: We started clinical screening and obligatory mask wearing for dialysis patients and personnel on 20-Feb-2020. However 11 symptomatic COVID-19 patients emerged till day +36. On days +39 and +40 a screening program was implied including measurement of SARS-COV-2 PCR and immunoglobulin G and M (IgG/IgM) and chest computerized tomography (CCT) scan. The results of CCT scan, classified according to the coronavirus disease 2019 (COVID-19) Reporting and Data System (CO-RADS) classification; as with very low (grade 1-normal), low, indeterminate, high, and very high likelihood of COVID-19 (grades 2, 3, 4, and 5; respectively), were used for compartmentalization of patients. RESULTS: Among 178 patients (68.2% male, mean age = 58.7 ± 16.6 years), 11 got COVID-19 before screening, two of whom died. CCT scans were normal in 71.3% and grade 2, 3, 4, and 5 in 7.9%, 4.5%, 5.6%, and 10.7%; respectively. PCR and IgG and/or IgM were positive in 27 and 32 patients. Eighty-three patients had evidence of COVID-19 infection, who were significantly older (62.2 ± 16.6 vs. 56.1 ± 16.02, P < .05). There was no difference in the rate of infection considering gender, diabetes mellitus, hypertension and different blood groups. CONCLUSION: Asymptomatic SARS- COV 2 infection may affect a large number of dialysis patients. We highly recommend a screening strategy whenever the number of patients is increasing.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Pessoal de Saúde , Unidades Hospitalares de Hemodiálise , Falência Renal Crônica/terapia , Pulmão/diagnóstico por imagem , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , Betacoronavirus/genética , Betacoronavirus/imunologia , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Incidência , Irã (Geográfico)/epidemiologia , Falência Renal Crônica/complicações , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Diálise Renal , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Adulto Jovem
12.
Maedica (Bucur) ; 15(2): 181-184, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32952682

RESUMO

Cardiovascular diseases are one of the most important causes of death globally. Results of recent studies have indicated that cytokine dysregulation was associated with premature coronary artery disease (P-CAD). The majority of cytokine gene polymorphisms influence the level of cytokine production and secretion. This study aimed to analyse IL-17 gene expression in patients with P-CAD and healty individuals in an Iranian population. This case-control study, conducted in Urmia University of Medical Sciences, compared patients with P-CAD hospitalised for risk of coronary artery stenosis, those admitted for medical cares and healthy normal controls. Thirty patients with P-CAD and 30 healthy individuals entered the study. The tested individulas were selected according to strict criteria such as clinical, echocardiogram, electrocardiogram and coronary angiography findings. Individuals with diabetes type 1 or 2 were excluded from the study. Reducing the diameter of at least one of the coronary arteries with more than 50% obstruction was selected as P-CAD. The qRT-PCR technique was used to determine the level of IL-17 gene expression in the studied groups. IL-17 gene expression was compared between the tested groups using t-test or Mann-Whitney U-test. Subjects' mean age (±SE) was 45(±5) and 44 (±4) among tested cases and related controls, respectively. The relative mRNA expression was 4.04±2.4 in patients with P-CAD and 2.75±1.3 in controls for IL-17. IL-17 gene expression was not significantly different in the tested groups (P> 0.05). IL-17 is not associated with risk of P-CAD in Iranian Turks.

13.
Expert Opin Drug Metab Toxicol ; 16(12): 1223-1231, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32905741

RESUMO

BACKGROUND: This research aimed at investigating the cyclosporine A intake impact with/without curcumin on podocyte protein gene expressions and matrix metalloproteins (MMPs) changes in rat kidney. METHODS: Thirty-two Wistar male rats were assigned to the control, sham, cyclosporine A, and cyclosporine A with curcumin groups. RESULTS: A significant increase was observed in CD2AP, ACTN4, podocin and also MMP9 and 2, cystatin C levels in the cyclosporine A group following treatment for four weeks, whereas a decrease was found in nephrin gene expression than the control group. In addition, a significant reduction was observed in the cyclosporine A group in glomerular filtration rate (GFR), urine creatinine, and increased plasma creatinine levels than the control group. Using curcumin plus cyclosporine A ameliorated gene expression alterations and increased the reduced amount of GFR, urine urea, and creatinine while reducing the increased plasma cystatine C, urea, and creatinine levels compared with the cyclosporine A group. CONCLUSION: Accordingly, cyclosporine A-induced kidney abnormalities are possibly associated with changes in podocyte intra- and extra-cellular protein gene expression that influence the quality of filtrated fluid via altering the foot process shape and slit diaphragm size. Finally, such impacts are reduced via curcumin as an antioxidant and anti-inflammatory compound.


Assuntos
Curcumina/farmacologia , Ciclosporina/toxicidade , Nefropatias/induzido quimicamente , Metaloproteínas/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Taxa de Filtração Glomerular , Imunossupressores/toxicidade , Nefropatias/prevenção & controle , Masculino , Podócitos/efeitos dos fármacos , Podócitos/metabolismo , Ratos , Ratos Wistar
14.
Iran J Basic Med Sci ; 23(6): 724-729, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32695287

RESUMO

OBJECTIVES: Stress during pregnancy is able to bring extensive effects on neurobehavioral development in offspring. The GABAergic system plays a pivotal role in neuronal excitability, which can be affected by prenatal stress (PS). This study aimed to evaluate impact of the PS on γ2 subunit of gamma-aminobutyric acid A (GABAA) receptor gene expression in the hippocampus and seizure induced by pentylenetetrazol (PTZ) in developing rats. MATERIALS AND METHODS: In this experimental study, female Wistar rats were exposed to restraint stress during gestation and their offspring were studied on postnatal days 14 and 21 (P14 and P21, respectively) for epileptic behaviors and γ2 GABAA receptor subunit gene expression. Quantitative real-time PCR was used for evaluating the γ2 GABAA receptor subunit gene expression in rat pups. Meanwhile, PTZ was injected into the pups, and seizure behaviors were recorded for 60 min. RESULTS: The results showed that γ2 subunit mRNA expression significantly increased in the hippocampus of the stressed pups. The expression level of γ2 subunit was higher on P21 compared to that on P14 in both groups. Number of seizures with tonic-clonic features increased in pups of stressed group compared to the control group. Prenatal stress significantly caused an increase in the total score of seizure on P21. CONCLUSION: The effect of PS on seizure susceptibility is age-specific; the increased γ2 subunit level in the hippocampus might be, at least in part, the underlying mechanism for PS-induced augmentation of seizures in immature rats.

15.
Rep Biochem Mol Biol ; 8(4): 401-406, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32582798

RESUMO

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a delayed-onset renal disorder that results from a mutation in the PKD1 or PKD2 genes. Autosomal dominant polycystic kidney disease results in end-stage renal disease due to renal cystic dysplasia. The aim of this study was to evaluate, by exon sequencing, the disease-causing variants of PKD2 (exons 4, 6, and 8) in Iranian ADPKD patients. METHODS: Genomic DNA was extracted from 3-5 ml of peripheral blood by the salting-out method. PKD2 exons 4, 6, and 8 were PCR-amplified and sequenced. RESULTS: Three disease-causing PKD2 variants were identified; all three were missense mutations in exon 4. The mutations were AGC → ACC (c.893G>C, cDNA.959G>C, S298T), TAC → TTC (c.1043A>T, cDNA.1109 A>T, Y348F), and GAA → GAT (c.1059A>T, cDNA.1125 A>T, E353D. These novel pathogenic variants may cause loss of the normal protein function. CONCLUSION: Our results suggest that AGC → ACC (c.893G>C, cDNA.959G>C, S298T), TAC → TTC (c.1043A>T, cDNA.1109 A>T, Y348F), and GAA → GAT (c.1059A>T, cDNA.1125 A>T, E353D variants are common in Iranian ADPKD patients. These mutations modify the transmembrane domain and likely influence PC2 function.

16.
Int Immunopharmacol ; 79: 106158, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31926479

RESUMO

Confident relationships between diabetes andliver damagehave previously been established. This study was designed to evaluate hepaticinflammation, apoptosis, and endocannabinoid system alterations in diabetes with or withouttropisetrontreatment. Rats were assigned to five equal groups: control, tropisetron, diabetes, tropisetron+diabetes, and glibenclamide+diabetes (n = 7 in each group). Rats were treated with tropisetron (3 mg/kg) and glibenclamide (1 mg/kg) as a positive control for two weeks after type 1 diabetes induction.Inflammatory cytokines tumor necrosis factor-alpha and interleukin 6 (TNF-α and IL-6) levels, apoptotic cells, and fatty acid amide hydrolase (FAAH) enzyme, at both transcriptional and protein levels increased, while the gene expression of cannabinoid receptor 1 (CB1) and its protein level decreased in the diabetic liver compared to the control. Treatment with tropisetron reversed TNF-α, apoptotic index, and endocannabinoid system components. These effects were equipotent with glibenclamide, indicating that tropisetroncan protect liver tissue against diabetic disturbances. These findings strongly support the idea that diabetes-induced liver abnormality is mediated by inflammatory reactions, apoptosis, and endocannabinoid system, and that these effects can be alleviated by using tropisetron as an antioxidant and anti-inflammatory agent.


Assuntos
Complicações do Diabetes/tratamento farmacológico , Endocanabinoides/metabolismo , Hepatite/tratamento farmacológico , Inflamação/tratamento farmacológico , Fígado/metabolismo , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Tropizetrona/uso terapêutico , Amidoidrolases/genética , Amidoidrolases/metabolismo , Animais , Apoptose , Humanos , Interleucina-6/metabolismo , Fígado/patologia , Masculino , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
17.
Rep Biochem Mol Biol ; 8(2): 102-110, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31832432

RESUMO

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a highly prevalent life-threatening monogenic disorder with high morbidity and mortality. Roughly 1:400-1000 individuals are affected with this disease worldwide. The development of ADPKD is largely attributed to mutations in the polycystic kidney disease (PKD)1 and PKD2 genes. However, the pathogenicity of the different polymorphisms in PDK1 in the development of ADPKD remains unclear. The aim of this study was to further elucidate the role of the polymorphisms in exon 25 of the PDK1 gene in relation to the pathogenesis of ADPKD in Iranian patients. METHODS: The genomic DNA of 36 Iranian patients with ADPKD was isolated using the standard salting out method. The PCR products were directly sequenced and analyzed. RESULTS: The frequencies of CAG>GAG, ATG>GTG, GTC>GTA, and GTG>ATG polymorphisms in exon 25 of the PKD1 gene were 34 (94.44%), 33 (91.67%), 26 (72.22%), and 5 (13.89%), respectively. The most frequent polymorphism associated with ADPKD was the homozygous CAG→GAG which causes an amino acid change of Q[Gln] to E[Glu] at codon 3005. CONCLUSION: Our data suggests that there is potentially a common polymorphism of PDK1 among the Iranian population with ADPKD. This may aid in the diagnosis and genetic screening of at-risk patients for ADPKD.

18.
J Cardiovasc Pharmacol ; 74(5): 420-425, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31356534

RESUMO

The study was conducted to evaluate the association between MMP-1 (rs1799750)-1607 1G/2G and MMP-3 (rs3025058)-1612 5A/6A polymorphisms/haplotypes and coronary artery disease (CAD) risk among Iranian Turks. Totally, 102 patients with CAD and 102 healthy subjects joined the study. Genomic DNA isolation was carried out using "salting out" method from 3 to 4 mL of whole blood samples. The MMP-1 (-1607 2G/1G) and MMP-3 (-1612 5A/6A) promoter gene polymorphisms were detected via polymerase chain reaction restriction fragment length polymorphism. Our results indicated that the frequencies of the MMP-1 (-1607) 2G alleles and 2G/2G genotypes and the MMP-3 (-1612) 6A alleles and 6A/6A genotypes were higher in CAD patients older than 50 years than in healthy controls (P < 0.05). We failed to show statistically significant differences between the CAD patients younger than 50 years and controls concerning MMP-1 -1607 ins/delG (1G > 2 G, rs1799750) and MMP-3 -1612 ins/delA (5A/6A, rs3025058) polymorphisms (P > 0.05). The frequencies of MMP-3/MMP-1 haplotypes were not statistically different among tested groups (P > 0.05). This examination, as the first study of its own kind in Iranian Turks, reported association between MMP-1 (rs1799750) -1607 2G/2G and MMP-3 (rs3025058) -1612 6A/6A genotypes and CAD risk in patients older than 50 years.


Assuntos
Doença da Artéria Coronariana/genética , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , Polimorfismo de Nucleotídeo Único , Adulto , Fatores Etários , Idoso , Estudos de Casos e Controles , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etnologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Fenótipo , Medição de Risco , Fatores de Risco , Turquia
19.
Maedica (Bucur) ; 14(4): 327-331, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32153662

RESUMO

10-Hydroxy-2-decenoic acid (10-HDA) as the main component of royal jelly has pharmacological characteristics. But the influence of 10-HDA on skin photoaging and photo damage is poorly understood. In the present study, we used 10-HAD immediately after UVA exposure and tested the effects on the attenuation of LMNAÄ150 expression in cultured human dermal fibroblasts Human dermal fibroblasts (cultured cells) were exposed to UVA irradiation. The mRNA level of LMNAÄ150 was determined by Taqman Real-Time PCR Assay. Real-time PCR analysis of LMNAÄ150 transcripts indicated that the level of LMNAÄ150 transcripts was higher in the UVA exposed group than the group treated with 10-HAD after UVA exposure (>8.22-fold). The LMNAÄ150 expression is down-regulated in human dermal fibroblasts after treatment with 10-HDA. It can be concluded that treatment with 10-HDA suppresses the UVA-induced gene expression of LMNAÄ150 and protects skin from UVA-induced photoaging and photo damage.

20.
Artigo em Inglês | MEDLINE | ID: mdl-29977872

RESUMO

Background: Some genetic factors are involved in the etiology of Hashimoto thyroiditis and Graves' disease as autoimmune thyroid diseases (AITDs). Effects of vitamin D receptor gene polymorphisms in AITDs development have already been investigated in some previous studies. However, no study has been done on the association between VDR FokI and ApaI polymorphisms and AITDs in an Iranian population. In this study, the possible effects of FokI and ApaI polymorphisms on AITDs were investigated in the population of northwest of Iran. Methods: A total of 121 AITDs adult patients and 117 healthy controls matched by age and sex in the same population were included in this study. FokI and ApaI polymorphisms were genotyped by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). Chi-square test and odds ratio (OR) with 95% CI were used to analyze the data. Results: FokI and ApaI genotypes frequencies were not significantly different between the 2 groups (p= 0.06, p= 0.73, respectively). However, FokI "CC" and "CT" genotypes were related to AITDs risk (p= 0.03; OR= 3.75; 95% CI, 1.16-12.17 and p= 0.04; OR= 3.41; 95% CI, 1.03-11.28, respectively). Conclusion: These data suggest that FokI polymorphisms are involved in AITDs susceptibility in the population of northwest of Iran.

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