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جستجوی مقالات مرتبط با کلیدواژه « sirt1 » در نشریات گروه « پزشکی »

  • اسکندر گرمه ای، علی یعقوبی*، نجمه رضائیان
    سابقه و هدف

    آتروفی عضلات اسکلتی ناشی از آسیب طناب نخاعی (SCI) می تواند باعث اختلال در عملکرد متابولیک سیستمیک به صورت ثانویه، مانند عدم تحمل گلوکز، دیابت نوع 2 و مقاومت به انسولین شود. از طرف دیگر گیرنده فعال کننده تکثیر پروکسی زوم گاما هم فعال ساز-1 آلفا (PGC-1α)، سیرتوئین-1 (SIRT1)، عوامل شناخته شده و پروتئین های مرتبط درگیر در آتروفی عضلات اسکلتی می باشند. بنابراین هدف از تحقیق حاضر بررسی اثر تمرین هوازی همراه با مصرف رزوراترول بر سطح SIRT1 و PGC-1α در عضله دوقلو موش های صحرایی بعد از آسیب طناب نخاعی بود.

    مواد و روش ها

    در این مطالعه تجربی، تعداد 36 سر رت نر نژاد ویستار با سن هشت هفته به صورت تصادفی در 4 گروه شامل کنترل، رزوراترول، تمرین و رزوراترول+تمرین (هر گروه 9 سر) قرار داده شدند. پس از بی هوشی، یک برش در خط وسط و روی برجستگی های مهره ای ایجاد شد، سپس عضلات و لامینای مهره T9 بدون آسیب رساندن به سخت شامه برداشته شد، آسیب نخاعی با اعمال ضربه توسط وزنه ده گرمی از ارتفاع 25 میلی متری بر روی نخاع در قطعه T10 ایجاد گردید. بعد از اطمینان از آسیب نخاعی، رزوراترول با دوز 10 میلی گرم به ازای هر کیلوگرم به صورت درون صفاقی و روزانه (هر روز صبح به مدت 4 هفته) تزریق شد. به موش های سایر گروه ها به مقدر مشابه سالین تزریق گردید. تمرین هوازی به کمک سیستم حمایت وزن، به مدت 4 هفته، هر هفته 5 جلسه، هر جلسه 58 دقیقه و با شدت 20 متر در دقیقه انجام شد. 48 ساعت پس از آخرین جلسه تمرین عضله دوقلو پای راست تمامی موش های صحرایی برداشته شد. سطح SIRT1 و PGC-1α عضله دوقلو به روش الایزا اندازه گیری شد. نتایج با استفاده از آزمون آنالیز واریانس یک طرفه و آزمون تعقیبی LSD تحلیل شد.

    یافته ها

    سطح SIRT1 عضله دوقلو موش های مبتلا به SCI در گروه های رزوراترول و تمرین + رزوراترول نسبت به گروه کنترل بالاتر بود (مقادیر P به ترتیب 00/23 و00/07)، اما سطح این شاخص با وجود افزایش در گروه تمرین نسبت به گروه کنترل تفاوت معنی داری مشاهده نشد (0/399=P). سطح SIRT1 عضله دوقلو در موش های مبتلا به SCI گروه تمرین+ رزوراترول به طور معنی داری نسبت به گروه تمرین بالاتر بود (0/038=P). سطح PGC-1α عضله دوقلو موش های مبتلا به SCI در گروه های تمرین و تمرین + رزوراترول نسبت به گروه کنترل بالاتر بود (مقادیر P به ترتیب 0/024 و 00/07)، اما سطح این شاخص با وجود افزایش در گروه رزوراترول نسبت به گروه کنترل تفاوت معنی داری مشاهده نشد (0/499=P). سطح PGC-1α عضله دوقلو در موش های مبتلا به SCI گروه تمرین+ رزوراترول به طور معنی داری نسبت به گروه رزوراترول بالاتر بود(0/023=P).

    استنتاج

    این نتایج نشان دهنده تاثیر مثبت مصرف رزوراترول بر سطح SIRT1 و هم چنین تمرین هوازی بر سطح PGC-1α عضله دوقلو در موش های مبتلا به SCI می باشد. اشاره شده است که افزایش بیان SIRT1 و افزایش PGC-1α متعاقب آن را در پی دارد که منجر به افزایش تعداد میونوکلئوس ها می شود که روند ترمیم پس از آسیب را بهبود می بخشد و با تنظیم افزایشی و کاهش فرآیندهای کاتابولیک در هیپرتروفی عضلانی نقش فعالی دارد. بنابراین تمرین هوازی همراه با مصرف رزوراترول می تواند با تاثیر بر سطح SIRT1 و PGC-1α عضلانی از آتروفی ایجاد شده در اثر آسیب نخاعی در عضلات پایین تر از سطح آسیب، جلوگیری نماید.

    کلید واژگان: تمرین هوازی, رزوراترول, SIRT1, PGC-1Α, آسیب نخاعی}
    Eskandar Garmei, Ali Yaghoubi*, Najmeh Rezaeian
    Background and purpose

    Atrophy of the skeletal system caused by spinal cord injury (SCI) can cause secondary systemic metabolic dysfunction, such as glucose intolerance, type 2 diabetes, and insulin resistance. On the other hand, Sirtun1 (SIRT1) and Peroxisome Proliferator-Activated Receptor-Gamma Coactivator-1alpha (PGC-1α) are known factors and related proteins involved in skeletal muscle atrophy. Therefore, the present study aimed to investigate the effect of aerobic training with resveratrol consumption on SIRT1 and PGC-1α levels in the gastrocnemius muscles of rats after spinal cord injury.

    Materials and methods

    36 male Wistar rats aged eight weeks were randomly placed in 4 groups including control, resveratrol, training, and resveratrol+training (each group n=9). After anesthesia, an incision was made in the midline of the back and over the vertebral ridges. The muscles and lamina of the T9 vertebra were removed without damaging the dura mater, Spinal cord injury was caused by dropping a ten-gram weight from a height of 25 mm on the spinal cord in the T10 segment. After confirmation of SCI, a Resveratrol supplement with a dose of 10 mg/kg was injected intraperitoneally and daily (every morning for 4 weeks), and the rats of other groups were injected with the same amount of saline. The aerobic training was carried out with the help of the weight support system for 4 weeks, 5 sessions per week, each session was 58 minutes and the intensity was 20 m/min. 48 hours after the last training session, the gastrocnemius muscle of right leg of all rats was removed. The SIRT1 and PGC-1α levels in the gastrocnemius muscle were measured by the ELISA method. To analyze the data, one-way analysis of variance and LSD post hoc tests were used at the significance level of P<0.05.

    Results

    SIRT1 levels in the gastrocnemius muscle of resveratrol and resveratrol+training groups were significantly higher than the control group (P-value respectively 0.023 and 0.007), but despite the increase in the level of this index in the training group compared to the control group, no significant difference was observed (P=0.399). SIRT1 levels in gastrocnemius muscle of resveratrol+training groups were significantly higher than training group (P=0.038). PGC-1α levels in gastrocnemius muscle of training and resveratrol+ training groups were significantly higher than control group (P-value respectively 0.024 and 0.007), but despite the increase in the level of this index in the resveratrol group compared to the control group, no significant difference was observed (P=0.449). PGC-1α levels in gastrocnemius muscle of resveratrol+training groups were significantly higher than reveratrol group (P=0.023).

    Conclusion

    These results show the positive effect of resveratrol consumption, on SIRT1 level, as well as aerobic exercise on PGC-1α level of the biceps muscle in rats with SCI. It has been pointed out that the increase in SIRT1 expression and the subsequent increase in PGC-1α leads to an increase in the number of myonuclei, which improves the recovery process after injury and plays an active role in muscle hypertrophy by upregulating and reducing catabolic processes. herefore, it appears that a combination of aerobic training and resveratrol supplementation can mitigate muscle atrophy caused by spinal cord injury in muscles below the level of injury by influencing the levels of muscle SIRT1 and PGC-1α

    Keywords: Aerobic Training, Resveratrol, SIRT1, PGC-1Α, Spinal Cord Injury}
  • Leila Kohan *, Sahar Sharghi, Afshin Karimi
    Aim
    Oxidative stress is one of the main factors has been implicated in pathophysiology of cataracts. Superoxide dismutase (SOD) can prepare the first line of defense versus detrimental reactive oxygen species (ROS) and Sirtuin (SIRT) confers protection against oxidative stress and retinal degeneration. Correlation of SOD1-50bp ins/del and SIRT1-rs7895833 polymorphisms with risk of cataracts is not studied currently. Therefore, we aimed to explore possible relationship between SOD1 (50bp ins/del) and SIRT1 (rs7895833) polymorphisms with the risk of cataracts in Iranian population. 
    Methods
    Our study design consisted of 200 patients with age-related cataracts and 200 healthy individuals as a control group. After DNA extraction, the identification of polymorphisms was conducted using PCR-based methods and data analysis was done by SPSS software. 
    Results
    A significant difference in SOD1 DD genotype distribution was observed between studied groups (OR: 3.42, P:0.037), the D allele was more frequent in patients in comparison with controls (OR: 1.68, P:0.009). Also, in the dominant genetic model for the D allele (comparison between ID+DD vs. II), ID+DD genotypes increased the risk of cataracts (OR: 1.62, P: 034). The association between SIRT1-rs7895833 polymorphism and cataract was significant in the AG genotype (OR: 2.37, P<0.001) and G allele (OR: 1.97, P<0.001). The SIRT1-1 polymorphism increased the risk of cataracts in the dominant tested inheritance model (OR: 2.34, P<0.001). In the combined analysis of two polymorphisms, there is an additive effect of the high-risk putative alleles about the risk of cataracts. Risk estimation according to the number of high-risk alleles showed that χ2 for linear trend for 0, 1, 2, 3 and 4 putative high-risk alleles is equal to 20.10 (P<0.001). 
    Conclusion
    The results showed that for the first time, SIRT1 rs7895833 and SOD1-50bp ins/del gene variations had additive effects on the risk of cataracts.
    Keywords: Oxidative stress, SOD1, SIRT1, Polymorphism, Cataract}
  • Fatemeh Javani Jouni*
    Background

    The SIRT1 gene is involved in many physiological activities of the body, including inflammation, innate and acquired immune system responses, neurodegeneration, age-related disorders, life-span extension, obesity, and heart disease. But its role in cancer is not yet fully understood. Considering the possible role of Lnc-OC1 in the regulation of SIRT1 and tumorigenesis, this study was designed and performed to evaluate the expression of SIRT1 and Lnc-OC1 genes in patients with breast and colorectal cancer.

    Methods

    In this case-control study, during September 2018 to July 2021, 84 patients (47.61%≤60 years, 52.38 >60 years) with breast cancer and 59 patients (42.37% ≤ 60 years, 57.62> 60 years) with colorectal cancer confirmed by pathological findings and the expression of SIRT1 and Lnc-OC1 were assessed using Quantitative real-time PCR.

    Results

    In colorectal cancer, it appears that increasing the expression of Lnc-OC1, decreased the expression of SIRT1. The expression of Lnc-OC1 gene in patients with breast and colorectal cancer has increased compared to normal tissue. The expression of SIRT1 in patients with breast cancer increased significantly compared to normal tissues, but decreased in patients with colorectal cancer.

    Conclusion

    The results showed that Lnc-OC1 could be used as an early diagnosis for colorectal cancer by reducing SIRT expression, and the expression of these two genes could be used to assess the prognosis for breast cancer.

    Keywords: SIRT1, Lnc-OC1, Breast cancer, Colorectal Cancers}
  • Farhad Eisvand, Kasra Rezvani, Hossein Hosseinzadeh, Bibi Marjan Razavi *
    Objective (s)

    Diabetes is a chronic disorder that occurs as a result of impaired glucose metabolism. In hyperglycaemic states, the balance between oxidative stress and antioxidant enzymes is disrupted leading to oxidative damage and cell death. In addition,  impaired autophagy leads to the storage of dysfunctional proteins and cellular organelles in the cell. Hence, the cytoprotective function of autophagy may be disrupted by high glucose conditions. Alpha-mangostin (A-MG) is an essential xanthone purified from the mangosteen fruit. The different pharmacological benefits of alpha-mangostin, including antioxidant, anti-obesity, and antidiabetic, were demonstrated. 

    Materials and Methods

    We evaluated the protective influence of A-MG on autophagic response impaired by high concentrations of glucose in human umbilical vein endothelial cells (HUVECs). The HUVECs were treated with various glucose concentrations (5-60 mM) and A-MG (1.25-10 μM) for three days. Then, HUVECs were treated with 60 mM of glucose+2.5 μM of A-MG to measure viability, ROS, and NO content. Finally, the levels of autophagic proteins including LC3, SIRT1, and beclin 1 were evaluated by western blot.

    Results

    The results expressed that high glucose condition (60 mM) decreased viability and increased ROS and NO content in HUVECs. In addition, LC3, SIRT1, and beclin 1 protein levels declined when HUVECs were exposed to the high concentration of glucose. A-MG reversed these detrimental effects and elevated autophagic protein levels.

    Conclusion

    Our data represent that A-MG protects HUVECs against high glucose conditions by decreasing ROS and NO generation as well as increasing the expression of autophagy proteins.

    Keywords: Alpha-mangostin, Autophagy, Beclin 1, Diabetes, Garcinia mangostana, HUVEC, LC3, SIRT1}
  • Havva Afshari, Shokoofe Noori *, Afshin Zarghi

    Non-alcoholic fatty liver disease (NAFLD) incidence and prevalence are rapidly increasing globally. The combined effects of metformin and quercetin (Que) have yet to be investigated. However, both have demonstrated the potential to reduce triglyceride (TG) levels and treat NAFLD by promoting autophagy. The objective of the present study was to elucidate the mechanism of action and assess the role of autophagy in the lipid-lowering effects of Que, both individually and in combination with metformin, in a HepG2 cell model of hepatic steatosis. Triglyceride levels and lipogenic gene expression were reduced in HepG2 cells exposed to palmitic acid (PA) when treated with Que-metformin, as evidenced by triglyceride measurements and real-time PCR. The LDH release assay also showed that this combination induced autophagy to protect HepG2 cells from PA-induced cell death. According to the Western blot analysis outcomes, Que-metformin increased LC3-I and LC3-II protein levels while decreasing p62 expression to induce autophagy. In HepG2 cells, the co-administration of Que-metformin elevated cAMP, phosphorylated AMP-activated protein kinase (p-AMPK), and Beclin-1 levels. Additionally, the inhibition of SIRT1 reversed the autophagy induced by Que-metformin. The findings of this study demonstrated for the first time that Que-metformin reduced hepatosteatosis by stimulating autophagy through the cAMP/AMPK/SIRT1 signaling pathway and diminishing inflammatory cytokines.

    Keywords: Hepatic Steatosis, Metformin, Quercetin, Autophagy, SIRT1, cAMP, AMPK}
  • Zhaohui Liu*, Yanli Meng, Yu Miao, Lili Yu, Qiannan Yu
    Introduction

    Sepsis-mediated acute lung injury (ALI) is a critical clinical condition. Artesunate (AS) is a sesquiterpene lactone endoperoxide that was discovered in Artemisia annua, which is a traditional Chinese herb. AS has a broad set of biological and pharmacological actions; however, its protective effect on lipopolysaccharide (LPS)-induced ALI remains unclear.

    Methods

    LPS-mediated ALI was induced in rats through bronchial LPS inhalation. Then NR8383 cells were treated with LPS to establish an in vitro model. Further, we administered different AS doses in vivo and in vitro.

    Results

    AS administration significantly decreased LPS-mediated pulmonary cell death and inhibited pulmonary neutrophil infiltration. Additionally, AS administration increased SIRT1 expression in pulmonary sections. Administration of a biological antagonist or shRNA-induced reduction of SIRT1 expression significantly inhibited the protective effect of AS against LPS-induced cellular injury, pulmonary dysfunction, neutrophil infiltration, and apoptosis. This demonstrates that enhanced SIRT1 expression is crucially involved in the observed protective effects.

    Conclusion

    Our findings could suggest the use of AS for treating lung disorders through a mechanism involving SIRT1 expression.

    Keywords: Artesunate, SIRT1, Lipopolysaccharide, Acute lung injury}
  • زهرا طهماسوند، شیما لرستانی، شکوفه نوری*
    سابقه و هدف

    کبد چرب غیر الکلی بیماری است که در صورت درمان نشدن به سیروز کبد منجر خواهد شد. کورکومین ماده موثره ریزوم گیاه زردچوبه است که دارای خواص آنتی اکسیدانی ضد التهابی ضد میکروبی و... است. در مطالعه حاضر اثرات آنالوگ کورکومین (FCur) بر بیان ژن های SIRT1 و FAS و تجمع تری گلیسیریدها در سلول های HepG2 چرب شده (مدل کبد چرب) بررسی شده است.

    روش کار

    در این مطالعه تجربی، پس از کشت سلول های  HepG2در محیط و شرایط مناسب، به منظور انتخاب دوز مناسب برای کورکومین و آنالوگ آن از تستMTT  استفاده شد. پس از چرب کردن سلول ها و تیمار آن ها با ترکیبات مورد نظر RNA استخراج و cDNA ساخته شد. سپس به منظور بررسی اثر کورکومین و آنالوگ آن روی بیان ژن های SIRT1 و FAS از Real- Time PCR استفاده شد. فعالیت SIRT1 با استفاده از یک کیت فلویورومتریک و میزان تری گلیسیرید داخل سلولی با استفاده از کیت تشخیص تری گلیسیرید نیز اندازه گیری شد و در نهایت به دلیل مقایسه بین بیش از دو گروه با یکدیگر نتایج با روش آماری t- Test وone way Anova  با 05/0p-value <  آنالیز قرار گرفت.

    یافته ها

    در اثر تیمار سلول های چرب شده HepG2  (مدل کبد چرب) با Cur، بیان نسبی ژن SIRT1 (0/8 ± 1/52) و فعالیت آنزیمی آن (0/7 ± 2/1) نسبت به گروه کنترل (برای بیان ژن: 1/79 ± 0/9 و برای فعالیت آنزیمی: 1/66 ± 0/8) به طور معنا داری، افزایش داشته است. در مقابل بیان نسبی ژن FAS (1/69 ± 0/6) نسبت به گروه کنترل (2/03 ± 0/8) و همچنین تری گلیسیریدهای تجمع یافته درون این سلول ها به طور معناداری کاهش داشته است. همچنین در گروه تیمار شده با FCur در مقایسه با گروه کنترل میزان بیان ژن (1/16 ± 2/76)  و فعالیت آنزیمی (1/21 ± 3/2) SIRT1 به طور معنا داری افزایش یافته است و میزان بیان ژن FAS (1/1 ± 0/2) در مقایسه با گروه کنترل کاهش معناداری داشته است. فعالیت آنزیمی SIRT1 در گروه FCur نسبت به Cur افزایش بیشتری داشته است، همچنین کاهش بیان ژن FAS در تیمار سلول ها با FCur در مقایسه با Cur به طورقابل ملاحظه ای بیشتر بوده است. کاهش چربی داخل سلولی در اثر تیمار با FCur در مقایسه با تیمار با Cur، تا حدودی بیشتر بود. (در تمام ارزیابی ها، برای کورکومین 0/01 p-value < و برای مشتق آن 0/001 p-value < است).

    نتیجه گیری

    به نظر می رسد که آنالوگ کورکومین (FCur) با توجه به دامنه وسیعی از فعالیت های فارماکولوژیک آن از جمله آثار آن روی متابولیسم لیپید در کبد، می توان به عنوان یک مکمل دارویی در درمان کبد چرب در کنار سایر روش های درمانی رایج بهره برد.

    کلید واژگان: کبد چرب غیر الکلی, کورکومین, FAS, HepG}
    Zahra Tahmasvand, Shima Lorestani, Shokoofe Noori*
    Background and Aim

    Non- alcoholic fatty liver is a disease that will lead to liver cirrhosis if not treated. Curcumin is the active substance of the rhizome of the turmeric plant, which has antioxidant, anti- inflammatory, antimicrobial, etc. properties. In the present study, the effects of curcumin analog on the expression of SIRT1 and FAS genes and the accumulation of triglycerides in fatty HepG2 cells (fatty liver model) have been investigated.

    Methods

    In this experimental study, after cultivating HepG2 cells in the right medium and conditions, the MTT test is used to choose the right dose for curcumin and it’s analog. After oiling the cells and treating them with the desired compounds, RNA was extracted and cDNA was made. Then, in order to investigate the effect of curcumin and its analog on the expression of SIRT1 and FAS genes, Real- Time PCR was used. SIRT1 activity was measured using a fluorometric kit and intracellular triglyceride levels were also measured using a triglyceride detection kit. And finally, the results were analyzed with t- test and one-way Anova statistical methods with p-value < 0.05.

    Results

    As a result of the treatment of HepG2 fatty cells (fatty liver model) with Cur, the relative expression of SIRT1 gene (1.52 ± 0.8) and its enzyme activity (2.1 ± 0.7) increased significantly compared to the control group (for gene expression: 0.9 ± 1.79 and for enzyme activity: 0.8 ± 1.66). On the other hand, the relative expression of the FAS gene (0.6 ± 1.69) compared to the control group (0.8 ± 2.03), as well as the accumulated triglycerides in these cells, and has decreased significantly. Also, in the group treated with FCur compared to the control group, the level of SIRT1 gene expression (2.76 ± 1.16) and enzyme activity (3.2 ± 1.21) increased significantly, and the level of FAS gene expression (0.2 ± 1.1) decreased significantly compared to the control group. The increase in SIRT1 enzyme activity in the FCur group has increased more compared to Cur, and the decrease in FAS gene expression in the treatment of cells with FCur has been significantly higher compared to Cur. The reduction of intracellular lipid was somewhat higher in the treatment with FCur compared to the treatment with Cur. (In all evaluations, p-value < 0.01 for curcumin and p-value < 0.001 for its derivative).

    Conclusion

    It seems that curcumin analog (FCur) can be used as a medicinal supplement in the treatment of fatty liver, along with other common treatment methods, due to its wide range of pharmacological activities, including its effects on lipid metabolism in the liver.

    Keywords: Non- alcoholic fatty liver, curcumin, SIRT1, FAS, HepG}
  • Abolfazl Nasiri, Sayed Mostafa Hosseini *, Mohsen Rashidi, Hadi Mozafari
    Objective
    War toxin, mustard gas, alkylating agent results in male infertility via inducing reactive oxygen species (ROS) production and DNA mutagenesis. SIRT1 and SIRT3 are multifunctional enzymes that involve in the DNA repair, oxidative stress responses. This study aim is to assess the correlation between serum levels of SIRT1, SIRT3 and both rs3758391T>C and rs185277566C>G gene polymorphisms with infertility in the war zones of Kermanshah province, Iran.
    Materials and Methods
    In this case-control study based on the semen analysis, samples were divided into two groups infertile (n=100) and fertile (n=100). High-performance liquid chromatography (HPLC) method was used to determine the malondialdehyde level, and also a sperm chromatin dispersion (SCD) test was used to evaluate the DNA fragmentation rate. Using the colorimetric assays, superoxide dismutase (SOD) activity was measured. SIRT1 and SIRT3 protein levels were determined by using ELISA. The genetic variants of SIRT1 rs3758391T>C, and SIRT3 rs185277566C>G, were detected by polymerase chain reaction-restriction fragment length (PCR-RFLP) technique.
    Results
    Malondialdehyde (MDA) level and the percentage of DNA fragmentation were higher in infertile samples, but serum levels of SIRT1 and SIRT3, and SOD activity was lower in infertile compared to fertile samples (P<0.001). The TC+CC genotypes and the C allele from SIRT1 rs3758391T>C polymorphism, and CG+GG genotypes and the G allele from SIRT3 rs185277566C>G polymorphism could increase risk of infertility (P<0.05).
    Conclusion
    The results of this study suggest that war toxins through the impact on genotypes, decreasing levels of SIRT1 and SIRT3 and increasing levels of oxidative stress, lead to defects in the concentration, motility and morphology of sperms and thus, infertility in men.
    Keywords: infertility, Oxidative stress, SIRT1, SIRT3, War Toxin}
  • Shiva Roshan Milani, Bagher Pourheydar, Saman Daneshfar, Leila Chodari*
    Purpose

     Reduced angiogenesis in the heart tissue is a primary risk factor for heart disease in the diabetes condition. This study was aimed to evaluate the changes of two main angiogenesis mediators, NADPH oxidase 4 (NOX4) and sirtuin 1 (SIRT-1) protein levels in the heart of diabetic rats and the impact of Insulin-like growth factor 1 (IGF-1) and exercise on these proteins.

    Methods

     Injection of 60 mg/kg of streptozotocin in 40 male Wistar rats led to the induction of type 1 diabetes. Angiogenesis was detected in the hearts by immunostaining for PECAM-1/ CD31 after 30 days of treatment with IGF-1 (2 mg/kg/day) and exercise. ELISA technique was utilized to establish the expression levels of NOX4 and SIRT-1 within the heart.

    Results

     The results revealed a significant increase in HbA1c and a significant decrease in SIRT1, NOX4 levels and angiogenesis grade in the heart of diabetes group compared to control group. Meanwhile, IGF-1 and exercise alone or in combination completely masked these effects. Additionally, synergistic effect on SIRT-1, HbA1c levels and angiogenesis grade is evident when IGF-1 and exercise are applied simultaneously.

    Conclusion

     Our findings suggest that reduction in angiogenesis in the heart of diabetic rats may be mediated by down expression of NOX4 and SIRT-1 protein levels. It was also displayed that IGF-1 and exercise as novel therapies increase NOX4 and SIRT-1 protein levels within the hearts of diabetic rats.

    Keywords: Diabetes, Heart, Angiogenesis, Exercise, IGF-I, NOX4, SIRT1}
  • مهدی بوستانی*، رعنا امیری، فاطمه مکی پور
    مقدمه و هدف

    پروتیین‌های سیرتویین در فرآیندهای متابولیک و هموستازی بدن درگیر می‌شوند و با فشار اکسایشی ناشی از سالمندی و بیماری‌های مربوط به سن مرتبط هستند. تغییرات این پروتیین‌ها در سالمندی و تاثیر فعالیت بدنی بر آنها کمتر مورد بررسی قرار گرفته است، از این رو هدف از مطالعه حاضر، بررسی تاثیر هشت هفته تمرین تناوبی بر سطوح پلاسمایی پروتیین‌های سیرتویین 1 و سیرتویین 3 مردان سالمند غیر‌ فعال بود.

    مواد و روش ها

    در این تحقیق 20 مرد سالمند غیر فعال با دامنه سنی 70-60 سال به صورت نمونه‌گیری در‌ دسترس انتخاب و به روش تصادفی ساده به دو گروه تجربی و کنترل تقسیم شدند. جهت بررسی تاثیر سالمندی بر سطوح پلاسمایی پروتیین‌های سیرتویین 1 و سیرتویین 3، 10 مرد جوان غیر‌ فعال به روش نمونه‌گیری هدفمند انتخاب شدند. برنامه تمرینی شامل هشت هفته تمرین تناوبی با شدت متوسط 50 درصد ضربان قلب ذخیره بر اساس اصل اضافه‌بار بود. سطوح پلاسمایی پروتیین‌های سیرتویین 1 و سیرتویین 3، در دو مرحله پیش‌آزمون و پس‌آزمون مورد اندازه‌گیری قرار گرفت. جهت مقایسه پیش‌آزمون از آزمون تحلیل واریانس یک راهه (آنوا) و مقایسه پس‌آزمون دو گروه سالمند تمرین و سالمند کنترل از آزمون تحلیل کوواریانس استفاده شد.

    نتایج

    تجزیه و تحلیل داده‌ها نشان داد که سطوح پلاسمایی پروتیین‌های سیرتویین 1 و سیرتویین 3 در گروه‌های سالمند نسبت به گروه جوان به طور معنی‌داری کمتر بودند (05/0>P). همچنین بر اثر هشت هفته تمرین تناوبی سطوح پروتیین‌های فوق به طور معنی‌داری افزایش یافت (05/0>P).

    نتیجه‌گیری: 

    با توجه به نتایج پژوهش حاضر به نظر می‌رسد که تمرین تناوبی با شدت متوسط با افزایش پروتیین های sirt1 و sirt3، می‌تواند فشار اکسایشی ناشی از سالمندی را کاهش دهد و منجر به افزایش دفاع آنتی‌اکسیدانی و بهبود کیفیت زندگی سالمندان شود.

    کلید واژگان: تمرین تناوبی, سالمندی, سیرتوئین1, سیرتوئین 3}
    Mehdi Bostani *, Raana Amiri, Fatemeh Makipour
    Background and Objective

     SIRT proteins are involved in the body's metabolic processes and homeostasis and are associated with oxidative stress due to aging and age-related diseases. Changes in these proteins in aging and the effect of physical activity on them have been less studied, so the aim of the present study was to investigate the effect of eight weeks of interval training on plasma levels of sirt1 and sirt3 proteins in inactive elderly men.

    Materials and Methods

     In this study, 20 inactive elderly men aged 70-60 years were selected by available sampling and divided into experimental and control groups by simple random sampling. To investigate the effect of aging on plasma levels of Sirt1 and Sirt3 proteins, 10 inactive young men were selected by purposive sampling. The training program consisted of eight weeks of interval training with a moderate intensity of 50% of the reserve heart rate based on the principle of overload. Plasma levels of Sirt1 and Sirt3 proteins were measured in two stages of pre-test and post-test. One-way analysis of variance (ANOVA) was used to compare the pre-test of the three groups and the analysis of covariance was used to compare the post-test of the two groups of training elderly and control elderly.

    Results

     The results showed that plasma levels of Sirt1 and Sirt3 proteins in the elderly group were significantly lower than the young group (P <0.05). Also, due to eight weeks of interval training, the levels of the above proteins increased significantly (P <0.05).

    Conclusion

    According to the results of this study, it seems that  moderate interval exercise with increasing the Sirt1 and Sirt3 proteins, can reduce the oxidative stress caused by aging and lead to increased antioxidant defense and improve the quality of life in the elderly.

    Keywords: Interval training, Aging, Sirt1, Sirt3}
  • خدیجه پورعبدی، فرشته شهیدی*، محمدرضا تابنده، مجتبی صالح پور
    مقدمه

    عملکرد میتوکندری در شرایط فیزیولوژیک و پاتولوژیک توسط چرخه ی روشنایی-تاریکی تنظیم می شود. ممکن است مداخلات تمرینی وابسته به زمان؛ با تنظیم هیپرگلیسمی، بر سلامت متابولیک بیماران مبتلا به دیابت تاثیر بگذارد. لیکن، اطلاعات محدودی در مورد ارتباط بین زمان تمرین و تنظیم مسیرهای شبانه روزی عضلانی در شرایط دیابت در دسترس است. این تحقیق با هدف بررسی تاثیر زمان تمرین در چرخه ی روشنایی- تاریکی بر بیان پروتیین SIRT1 و نسبت NAD+/NADH، در عضله دوقلوی موش های مدل دیابت نوع 2 انجام شد.

    مواد و روش ها

    در این تحقیق تجربی، تعداد سی سر موش نر سالم نژاد NMRI به طور تصادفی به سه گروه شاهد، دیابتی و دیابتی+تمرین تقسیم بندی شدند. دیابت نوع دو با استفاده از ترکیبی از رژیم غذایی پرچرب (5 هفته) و تزریق استرپتوزوتوسین (20 میلی گرم بر کیلوگرم وزن بدن) القا شد. سپس هشت هفته تمرین هوازی، با شدت متوسط (5 روز، 60-80 دقیقه) روی تردمیل در دو زمان متفاوت در اوایل مرحله روشنایی:ZT3)  در ساعت 9:00 صبح) و اوایل مرحله تاریکی:ZT15)  در ساعت 9:00 شب) انجام شد. عضله دوقلو در دو زمان تمرین جمع آوری و بیان پروتیین SIRT1 با روش وسترن بلات ارزیابی شد. محتوای NAD+/NADH سلولی و غلظت گلوکز با روش رنگ سنجی ارزیابی گردید. برای تجزیه و تحلیل داده ها از تحلیل واریانس دو-راهه استفاده شد.

    یافته ها

    هشت هفته تمرین هوازی فقط در اوایل مرحله تاریکی باعث افزایش معنی دار بیان پروتیین SIRT1 و سطح NADH (P< 0/001 ) و بهبود هایپرگلایسمی (0/005=P) شد. تمرین هوازی بصورت مستقل از زمان بر افزایش نسبت NAD+/NADH اثرگذار بود (0/003=P).

    نتیجه گیری

    زمان بندی مناسب تمرین در اوایل تاریکی، همزمان با تغییرات شبانه روزی پروتیین SIRT1 و سطح NAD+، ممکن است باعث تقویت اثرات تمرین و اصلاح موثرتر هایپرگلایسمی شود.

    کلید واژگان: زمان بندی تمرین هوازی, ریتم شبانه روزی, دیابت نوع دو, SIRT1, NAD+, NADH}
    Khadijeh Pourabdi, Fereshteh Shahidi*, MohammadReza Tabandeh, Mojtaba Salehpour
    Introduction

    Mitochondrial function is regulated by the dark-light cycle under physiological and pathological conditions. Time-dependent exercise interventions may affect metabolic health in diabetic patients by regulating hyperglycemia. However, limited data are available about the correlation between the time of exercise and the regulation of muscle circadian rhythm in diabetes conditions. This study aimed to investigate the effect of time of exercise in the dark-light cycle on SIRT1 protein expression and the NAD+/NADH ratio in the gastrocnemius muscle of diabetic mice.

    Materials and Methods

    In this experimental study, thirty healthy male NMRI mice were randomly divided into three groups: control, diabetic, and diabetic+exercise. Type 2 diabetes was induced using a combination of a high-fat diet (five weeks) and streptozotocin injection (20 mg/kg body weight). Eight weeks of aerobic exercise with moderate intensity (5 days, 80-60 minutes) were performed on a treadmill at two times of the day, the early light phase (ZT3) at 9:00 AM and the early dark phase (ZT15) at 9:00 PM. Gastrocnemius muscles were collected at two times of the day, and SIRT1 protein expression was evaluated by Western blot analysis. The cellular NAD+/NADH content and glucose concentrations were measured using the colorimetric method. A two-way analysis of variance was used to analyze the data.

    Results

    Eight weeks of aerobic exercise significantly increased SIRT1 protein and NADH levels (P<0.001) and improved hyperglycemia (P=0.005) only in the early dark phase. Aerobic exercise increased the NAD+/NADH ratio independently of time (P=0.003).

    Conclusion

    Proper exercise timing in the early dark, along with SIRT1 protein and NAD+ level circadian changes, may strengthen the effects of exercise and correct hyperglycemia more effectively.

    Keywords: Aerobic exercise timing, Circadian rhythm, Type 2 diabetes, SIRT1, NAD+, NADH}
  • Farzaneh Babak, Sadegh Rajabi, MohammadHasan Sakhaie, Farideh Jalali Mashayekhi*
    Background and objectives

    Trimethyltin chloride (TMT) is a chemical with neurotoxic effects on central nervous system. Carvacrol is a phenolic monoterpenoid with antioxidative properties derived from oregano, thyme, and other plants. We aimed to explore carvacrol effects on TMT-induced oxidative damage focusing on nuclear factor erythroid 2-related factor 2 (Nrf2)/ kelch-like ECH associated protein 1 (Keap1)/antioxidant response element (ARE) pathway and Sirt1.

    Methods

    Thirty- two male rats were divided into four equal groups. Groups 1 and 2 received normal saline (control) and Dimethyl sulfoxide (DMSO, sham) for 21 days, respectively. Groups 3 and 4 were first treated with TMT (8 mg/kg) and then received normal saline and carvacrol (40 mg/kg) for 21 days, respectively. Finally, the levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidant status (TOS) in serums and expressions of Nrf2, heme oxygenase-1 (Ho-1), Keap1, NADPH quinone oxidoreductase (NQO-1) and Sirtuin1 (Sirt1) in the hippocampus of the rats were quantified.

    Results

    TMT significantly decreased Nrf2, HO1, NQO1, Sirt1 expressions and TAC level, while markedly increased expression of Keap-1 and levels MDA and TOS compared with control groups. Carvacrol treatment significantly upregulated Nrf2, HO1, NQO1, and Sirt1 along with an increase in TAC level as compared with TMT-treated rats. On the other hand, carvacrol caused a significant decrease in the expression of Keap-1 and levels of MDA and TOS compared with controls.

    Conclusion

    Our results suggested the potential neuroprotective effects of carvacrol on TMT-triggered neurotoxicity probably by reciprocal regulation of Keap1/Nrf2/ARE pathway and Sirt1 activity.

    Keywords: carvacrol, Keap1, Nrf2, sirt1, Trimethyltin Chloride}
  • سحر کوچکی، هاجر عباس زاده*، پروین فرزانگی
    مقدمه

    آزواسپرمی به عنوان عدم وجود اسپرم از مایع منی تعریف می شود. اسپرماتوژنز ممکن است بسیار حساس به ترکیباتی باشد که با متابولیسم انرژی میتوکندری و کنترل تنفس سلولی تداخل دارند. هدف پژوهش حاضر بررسی بیان ژن های SIRT1 و PGC-1α در بافت بیضه موش های آزواسپرمی شده با بوسولفان متعاقب یک دوره تمرینات شنا بود.

    روش کار

    در این مطالعه تجربی، 20 سر موش صحرایی نر بالغ نژاد ویستار پس از ایجاد مدل آزواسپپرمی به صورت تصادفی به چهار گروه کنترل سالم، شم، آزواسپرمی، تمرین+ آزواسپرمی دسته بندی شدند. گروه تمرین+ آزواسپرمی، یک ماه بعد از ایجاد آزواسپرمی، به مدت 8 هفته و هر هفته پنج روز و هر روز به مدت 30 دقیقه به انجام تمرین شنا با شدت پایین پرداختند. جهت تجزیه و تحلیل داده ها از آنالیز واریانس یکطرفه استفاده گردید.  

    یافته ها

    نتایج نشان داد که گروه آزواسپرمی نسبت به گروه کنترل سالم موجب کاهش معنادار سطح بیان ژن SIRT1 و PGC-1α می شود و 8 هفته تمرین هوازی شنا با شدت پایین موجب افزایش معنادار آن در گروه تمرین+ آزواسپرمی نسبت به گروه آزواسپرمی شده است.

    نتیجه گیری

    به طور کلی نتایج تحقیق حاضر بیانگر آن است که فعالیت ورزشی منظم هوازی مانند شنا با شدت پایین در مهار آثار ناشی از بیماری های ناباروری از طریق حفظ و توسعه بیوژنز میتوکندری در بهبود فرآیند اسپرماتوژنز کمک شایانی می کند.

    کلید واژگان: شنا, SIRT1, PGC-1α, آزواسپرمی}
    Sahar Koochaki, Hajar Abaszade*, Parvin Farzanegi
    Introduction

    Azoospermia is defined as the absence of sperm from semen. Spermatogenesis may be highly sensitive to compounds that interfere with mitochondrial energy metabolism and control of cellular respiration. The aim of this study was to evaluate the expression of SIRT1 and PGC-1α genes in testicular tissue of azoospermic rats treated with busulfan after a period of swimming training.

    Methods

    In this experimental study, 20 adult male wistar rats were randomly divided into four groups of healthy control: sham, azoospermia, exercise + azoospermia after azoospermia model was created. Exercise + azoospermia group, one month after azoospermia, performed low-intensity swimming exercises for 8 weeks, five days a week for 30 minutes each day. One-way analysis of variance was used to analyze the data.

    Results

    The results showed that azoospermia group significantly reduced the expression level of SIRT1 and PGC-1α genes compared to healthy control group and 8 weeks of low intensity aerobic training caused a significant increase in Azoospermia + exercise group compared to azoospermia group. Has been.

    Conclusion

    In general, the results of the present study indicate that regular aerobic exercise such as low-intensity swimming in controlling the effects of infertility through the maintenance and development of mitochondrial biogenesis helps to improve the process of spermatogenesis.

    Keywords: Swimming, SIRT1, PGC-1α, Azoospermia}
  • Nasim Abedimanesh, Morteza Nouri, Kosar Mohammadnejad, Maedeh Barati, Elham Dabardani, Elahe Kakavand, MohammadReza Eskandari, Seyed Hojjat Hosseini, Seyede Momeneh Mohammadi, Iraj Jafari Anarkooli, Maryam Noubarani, Sina Andalib, Alireza Yazdinezhad, Behrooz Motlagh* *
    Background and Objectives

    AMPK/SIRT1/PGC1α signaling pathway has an important role in diabetic condition. Some natural products exert anti-diabetic effects by modulating this pathway and also by inhibition of NF-κB. Vinca herbacea has potent antioxidant and anti-inflammatory activities In the present study, we investigated the effects of this plant on the AMPK/SIRT1/PGC1α axis and NF-κB genes expression as well as glucose, insulin levels and total antioxidant capacity in streptozotocin- induced diabetic rats.

    Methods

    Streptozotocin induced diabetic male Sprague-Dawley rats were assigned to six groups: control, diabetic, diabetic + different doses of Vinca herbacea extract (100, 200 and 400 mg/kg.b.w) and glibenclamide. Fasting blood glucose, serum insulin and total antioxidant capacity were measured. The histopathology of liver and pancreas were evaluated. Real-time PCR was performed to assess gene expression levels.

    Results

    Vinca herbacea extract (100 and 200 mg/kg.b.w) significantly reduced fasting blood glucose and 2-h blood glucose and increased serum insulin levels and total antioxidant capacity compared to the control diabetic rats. Also an improvement in lipid profile and liver enzymes levels was observed. According to the histopathological assay, different damages induced by streptozotocin to liver and pancreas tissues were largely eliminated by treatment with the extract. Vinca herbacea extract significantly upregulated the AMPK, SIRT1 and PGC-1α and downregulated the NF-κB mRNA expression compared to the diabetic control rats.

    Conclusion

    Anti-diabetic effects of V. herbacea extract were indicated in streptozotocin -induced diabetic rats. The AMPK/SIRT1/PGC1α/NF-κB signaling pathway was suggested as the mechanism involved in the protective effects of this extract in diabetes.

    Keywords: NF-κB, PGC1α, sirt1, Total Antioxidant Capacity, Vinca Herbacea}
  • Zeinab Hamidi-zad, Azam Moslehi*, Maryam Rastegarpanah
    Background and purpose

    Nonalcoholic steatohepatitis (NASH) is considered a common and serious liver disease, which develops into cirrhosis, fibrosis, and even hepatocellular carcinoma. Oxidative stress is identified as an important factor in the induction and promotion of NASH. Allantoin is a natural and safe compound and has notable effects on lipid metabolism, inflammation, and oxidative stress. Therefore, this study was aimed to assess the role of allantoin on the oxidative stress and SIRT1/Nrf2 pathway in a mouse model of NASH.

    Experimental approach

    C57/BL6 male mice received saline and allantoin (saline as the control and allantoin as the positive control groups). NASH was induced by a methionine-choline deficient diet (MCD). In the NASH-allantoin (NASH-Alla) group, allantoin was injected for 4 weeks in the mice feeding on an MCD diet. Afterward, histopathological, serum, oxidative stress, and western blot evaluations were performed.

    Findings/ Results

    We found NASH provided hepatic lipid accumulation and inflammation. Superoxide dismutase (SOD) and glutathione (GSH) levels decreased, lipid peroxidation increased, and the expression of SIRT1 and Nrf2 downregulated. However, allantoin-treatment decreased serum cholesterol, ALT, and AST. Liver steatosis and inflammation were improved. Protein expression of SIRT1 and Nrf2 were upregulated and SOD, CAT, and GSH levels increased and lipid peroxidation decreased.

    Conclusion and implications

    It seems that the antioxidant effects of allantoin might have resulted from the activation of SIRT1/Nrf2 pathway and increase of cellular antioxidant power.

    Keywords: Allantoin, NASH, Nrf2, Oxidative stress, SIRT1}
  • مرتضی ابراهیم زاده، کمال عزیزبیگی*، خالید محمد زاده سلامت، سامان پاشایی
    زمینه و هدف

    پژوهش های پیشین تاثیر مثبت تمرین هوازی و کورکومین بر متغیرهای مختلف در شرایط دیابت را نشان داده اند. ترکیب این دو مداخلات، ممکن است اثر هم افزایی بر متغیرهای فوق داشته باشد. پژوهش حاضر به بررسی اثر مستقل و ترکیبی تمرین هوازی و مکمل کورکومین بر بیان ژن SIRT1 عضله قلبی و غلظت رزیستین پلاسمایی موش های صحرایی دیابتی می پردازد.

    روش ها

    40 سر موش صحرایی نر به طور مساوی به گروه های کنترل سالم، کنترل دیابتی، تمرین دیابتی، کورکومین دیابتی و تمرین + کورکومین دیابتی تقسیم شدند. تمرین هوازی (پنج جلسه/هفته، هر جلسه 30 دقیقه با سرعت 22 متر/دقیقه، شیب: 5%) و مکمل دهی (30 میلی گرم/کیلوگرم وزن بدن، سه روز/هفته) به مدت هشت هفته انجام شد. 48 ساعت پس از دریافت آخرین مداخله، موش ها قربانی شدند.

    یافته ها

     دیابت باعث کاهش بیان ژن SIRT1 قلبی و افزایش غلظت غلظت رزیستین پلاسمایی شد (0/001= p ). تمرین باعث افزایش بیان SIRT1(0/044= p ) و کاهش غلظت رزیستین (0/001= p ) در موش های دیابتی شد. کورکومین نیز باعث افزایش بیان SIRT1 (0/048= p ) و کاهش غلظت رزیستین (0/001= p ) در موش های دیابتی شد. ترکیب تمرین و مکمل نسبت به تمرین تنها/مکمل تنها اثر معنی دار و بیشتری در افزایش بیان ژن SIRT1 و کاهش غلظت پلاسمایی رزیستین داشت (0/05 <p ).

    نتیجه گیری

     در موش های صحرایی دیابتی، انجام تمرین هوازی همراه با مصرف توام کورکومین نسبت به استفاده از هر یک به تنهایی، اثرات مفید فاحش تری بر بیان ژن SIRT1 عضله قلبی و غلظت پلاسمایی رزیستین دارد.

    کلید واژگان: تمرین هوازی, دیابت, رزیستین, کورکومین, SIRT1}
    Morteza Ebrahimzadeh, Kamal Azizbeigi*, Khalid Mohammadzadeh Salamat, Saman Pashaei
    Background and Aim

    Previous studies have shown the positive effect of aerobic exercise and curcumin on various variables in diabetes. Combination of these interventions may have an additive effect on these variables. The present study investigates the independent and combined effect of aerobic exercise and curcumin supplementation on cardiac SIRT1 gene expression and plasma resistin concentration in diabetic rats.

    Methods

    Forty male rats were equally divided into healthy control, diabetic control, diabetic exercise, diabetic curcumin, and diabetic curcumin+exercise. Aerobic exercise (five sessions/week, each session 30 minutes at a speed of 22 meters/minute, slope: five percent) and supplementation (30 mg/kg body weight, three days/week) were performed for eight weeks. Rats were sacrificed 48 hours after receiving the last intervention.

    Results

    Diabetes decreased the expression of cardiac SIRT1 gene (p=0.001) and increased plasma resistin concentration (p =0.001). Exercise increased the expression of SIRT1 gene (p= 0.044) and decreased the resistance of resistin (p = 0.001) in diabetic rats. Curcumin also increased SIRT1 gene expression (p=0.048) and decreased resistin concentration (p=0.001) in diabetic rats. Compared to exercise or supplementation, combination of exercise and supplementation had more significant effect on increasing the expression of SIRT1 gene and decreasing the plasma concentration of resistin (p < 0.05).

    Conclusion

    In diabetic rats, aerobic exercise combined with curcumin has more pronounced beneficial effects on myocardial SIRT1 gene expression and plasma resistin concentrations from each alone.

    Keywords: Aerobic exercise, Diabetes, Resistin, Curcumin, SIRT1}
  • Shaheen Bibi, Fayyaz Ahmad, Muhammad Rizwan Alam, Muhammad Ansar, Sun Yeou Kim, Hussain Mustatab Wahedi*
    Timely repair of damaged skin is very important to maintain the integrity and homeostasis of skin, but the wound healing process is compromised in diabetic patients due to several extrinsic and intrinsic factors thus lead to leg amputation and death eventually. Sirtuins, a family of seven conserved proteins are known to be associated with pathophysiological processes of the skin. The most important among them are sirt1and sirt3 involved in cell regeneration and cell survival. Naphthoquinone derivatives have a wide range of therapeutic properties, but the potential diabetic wound healing activity of lapachol has not been identified yet. The present study thus aimed to investigate the wound healing effects of lapachol in a diabetic mouse model. Diabetic wounded mice were divided into 3 groups; vehicle, lapachol 0.05%, and lapachol 0.1%. Skin samples collected from diabetic wounded mice on different time points after treatment for 10 consecutive days were subjected to downstream analysis by western blot, ELISA and histology. Lapachol treatment was found to enhance the expression of sirt1/sirt3 and other proteins involved in cell migration and blood vessel formation. The tissue development rate was increased by lapachol treatment with better collagen deposition. Interestingly, lapachol treatment also gave rise to a high concentration of growth factors resulting in speedy and timely recovery of injured skin. In summary, our findings suggest that lapachol promotes efficient wound healing in a diabetic mouse model by increasing the expression of sirt1 and sirt3 and other proteins related to wound repair and skin regeneration including α-PAK, RAC1/CDC42, VEGF and growth factors viz PDGF and VEGF. This research work finds a novel potential activator of sirtuins in the form of lapachol and depicts the role of activated sirtuins in diabetic wound healing.
    Keywords: Lapachol, Sirt1, Sirt3, Diabetic wound healing, skin}
  • Qing Hua Yin, Yuan Zhou, Zhi Yuan Li
    Objective

    Our study aimed to investigate function and mechanism of miR-373 in proliferation and apoptosis of pancreatic cancer (PC) cells by regulating NAD+-dependent histone deacetylase sirtulin 1 (SIRT1).

    Materials and Methods

    This experimental study included two PC cell lines AsPC-1 and PANC-1 in which expression levels of miR-373 and SIRT1 were manipulated. The level of miR-373 was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) method. Expression levels of SIRT1, BCL-2, BAX, cleaved CASPASE-8/9/3, PARP, PGC-1α, NRF2, eNOS and iNOS were examined via RT-qPCR and western blotting, respectively. The binding sites of miR-373 on the SIRT1 were examined via dual-luciferase assay. Cell proliferation and apoptosis were examined by MTT assay, colony formation assay, Annexin-V/PI staining and TUNEL assay. The oxidative metabolic changes were monitored by reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) detection.

    Results

    miR-373 could specifically target the 3’-UTR of SIRT1 and reduce its expression in PC cells. Either elevated expression of miR-373 or partial loss of SIRT1 inhibited cell proliferation and induced cell apoptosis. Accumulation of BAX and cleaved CASPASE-8/9/3, inhibition of PGC-1α/NRF2 pathway, increase oxidative stress and reduction of BCL-2 as well as uncleaved PARP were found in the presence of miR-373 or the absence of SIRT1. Overexpression of SIRT1 could reduce anti-proliferative and pro-apoptotic effects of miR-373.

    Conclusion

    Overall, this study concluded that miR-373-dependent SIRT1 inhibition displays anti-proliferative and proapoptotic roles in PC cells via PGC-1α/NRF2 pathway, which highlights miR-373 as a potential target for PC treatment.

    Keywords: miR-373, Oxidative Stress, Pancreatic Cancer, PGC-1α, NRF2 Pathway, SIRT1}
  • Abolfazl Nasiri *, Asad Vaisi-Raygani, Zohreh Rahimi, Mitra Bakhtiari, Fariborz Bahrehmand, Amir Kiani, Hadi Mozafari, Tayebeh Pourmotabbed
    Background
    Reactive oxygen species (ROS) play a crucial role in etiology of DNA fragmentation and lipid peroxidationin sperm, leading to infertility in men. The silent information regulators SIRT1 and SIRT3 are members of thesirtuins protein family known to be involved in cancer genetics, aging and oxidative stress responses. The aim ofthisstudy is to determine the correlation between SIRT1 and SIRT3 with antioxidants, oxidative stress biomarkers, andDNA fragmentation in the semen of asthenoteratozoospermic and normozoospermic men.
    Materials and Methods
    In this case-control study, after spermogram analysis the specimens were divided intotwo groups, normozospermic (n=40) and asthenoteratozoospermic (n=40), according to World Health Organization(WHO) standards. Sperm DNA fragmentation was evaluatedusing the sperm chromatin dispersion (SCD) test.Catalaseactivity was measured using the Aebi spectrophotometeric method. Total antioxidant capacity (TAC) level and superoxidedismutase (SOD) activitywere measured by using commercially available colorimetric assays. Enzyme-linkedimmune sorbent assay (ELISA) was used to measure SIRT1 and SIRT3 protein levels of seminal plasma. Malondialdehyde(MDA) level in seminal plasma was determined by high-performance liquid chromatography (HPLC).
    Results
    The asthenoteratozoospermic group had significantly lower catalase and SOD activities and TAC levels incomparison with the normozoospermic group (p <0.001).The percentage of DNA fragmentation and MDA level in theasthenoteratozoospermic group were remarkably higher than in the normozoospermic group. The SIRT1 and SIRT3protein levels in seminal plasmawere remarkably lower in asthenoteratozoospermic group than the normozoospermicgroup (p <0.001).
    Conclusion
    The results of this study suggest that SIRT1 and SIRT3 protein levels are negatively correlated withoxidative stress and DNA fragmentation in semen. The low levels of SIRT1 and SIRT3 in asthenoteratozoospermicmen may lead to an increase in oxidative stress, DNA fragmentation, and lipid peroxidation that eventually result inimmotile and immature spermatozoa (asthenoteratozoospermia).
    Keywords: DNA fragmentation, infertility, Oxidative stress, SIRT1, SIRT3}
  • مهرنوش مهرو، حمزه اکبری بوکانی*، علی اصغر رواسی، سیروس چوبینه
    مقدمه و اهداف

    پروتئین SIRT1 به عنوان عضوی از خانواده سیرتویین عامل کلیدی موثر در بسیاری از عملکردهای بیولوژیکی از قبیل طول عمر، فشارهای اکسایشی و فرآیند استخوان سازی در تعامل با فعالیت بدنی مورد بررسی قرار می گیرد. مطالعه حاضر با هدف مقایسه تاثیر دو نوع تمرین ورزشی ترکیبی چندجزیی و ایزومتریک بر میزان پلاسمایی  SIRT1در زنان مبتلا به استیوپنیا بود.

    مواد و روش ها

    بدین منظور تعداد 45 زن 50 الی 60 ساله با T-score شاخص استیوپنیا بین 1- و 2/5- که معیار ورود به مطالعه ی حاضر را داشتند، از طریق فراخوان و مصاحبه انتخاب شدند و به صورت تصادفی به سه گروه 15 نفره شامل دو گروه تمرینی و یک گروه کنترل تقسیم شدند. پس از گروه بندی آزمودنی ها و خون گیری اولیه، گروه تمرین ترکیبی بین 45 تا 90 دقیقه (تمرینات کششی، قدرتی و هوازی) و گروه تمرینات ایزومتریک بین 20 تا 40 دقیقه در هر جلسه (زمان، تعداد ست و مدت زمان هر انقباض مشخص)، سه جلسه در هفته به مدت 12 هفته مشغول به تمرین شدند. برای مقایسه ی اختلافات موجود بین پیش آزمون و پس آزمون، از آزمون t زوجی و تحلیل واریانس یک راهه و آزمون تعقیبی توکی در سطح معناداری (0/05) استفاده شد.

    یافته ها

    نتایج به دست آمده از تکنیک الیزا نشان داد که در مراحل پس آزمون اختلاف معناداری بین میانگین سطوح SIRT1 در سه گروه وجود داشت (0/01=P). هر دو شیوه ی تمرین موجب تغییرات مثبت در سطوح SIRT1 در مقایسه با گروه کنترل شد (0/001=P)، اما دو گروه تمرینات ورزشی ایزومتریک و ترکیبی با همدیگر اختلاف معناداری در اثربخشی بر روی سطوح SIRT1 نداشتند (0/997=P).

    نتیجه گیری

    به نظر می رسد بالا بودن سطوح SIRT1 در افراد سالمند یک مکانیسم جبرانی جهت مقابله با استرس های اکسیداتیو و همچنین پر کردن جای خالی فاکتورهای رشدی نظیر IGF-1 در دوران پیری بوده و تمرینات ورزشی ایزومتریک و ترکیبی هر دو به عنوان یک محرک اصلی می توانند اثرات مثبتی بر سطوح SIRT1 در زنان مبتلا به استیوپنیا داشته باشند.

    کلید واژگان: استئوپنیا, زنان پیش سالمند, سیرتوئین-1, تمرین ایزومتریک, تمرین ترکیبی}
    Mehrnoosh Mahrou, Hamze Akbari Boukani *, AliAsghar Ravasi, Sirus Choobineh
    Background and Aims

    SIRT1 protein has been investigated as a key factor in many biological functions, such as longevity, oxidative stress, and bone mass in interaction with physical activity. The purpose of the present study was to compare the effect of combined and isometric exercise training on plasma level of SIRT1 in elderly women with osteopenia.

    Materials and Methods

    For this purpose, 45 women, aged 50-60 years, with osteopenia who were eligible for the present study, were selected and randomly divided into three groups of 15, each consisting of two exercise groups (Combined group and Isometric group) and one control group. After grouping the participants' initial blood sampling, Co group was trained 45-90 min per session (stretch, strength, endurance) and Iso group was trained 20-40 min (set, frequency, contraction time), three sessions per week, for 12 weeks. Data were analyzed using SPSS, version 24, running using paired t-test, One-way ANOVA, and Tukey post hoc test with the significance level set at 0.05.   

    Results

    The ELISA results showed that both exercise methods had significant effects on SIRT1 compared to baseline (p=0/01). There was a significant difference between the two methods of training with control group on SIRT 1 level in the elderly women with osteopenia (p=0/001), but the difference between the two was not statistically significant (p=0/979). 

    Conclusion

    It seems that elevated SIRT1 level in aged people is compensatory mechanism of stress oxidative system and decreased activity in growth factor such as IGF1 in old age. It can be concluded that combined and isometric exercise could have positive effects on SIRT1 level in elderly women with osteopenia.

    Keywords: Osteopenia, Pre-elderly women, Sirt1, combined exercise, isometric exercise}
نکته
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