CircPAN3/miR-221/PTEN axis and apoptosis in myocardial Infarction: Quercetin's regulatory effects.

The circular RNA/microRNA/mRNA axis is a new layer of non-coding RNA(ncRNA)-based regulatory gene expression networks upstream of numerous cell signaling pathways. Circular RNAPAN3 (circPAN3) is involved in autophagy, fibrosis and apoptosis which are responsible for the reduction incardiac functional capacityfollowingmyocardial infarction(MI). However, the molecular mechanism of circPAN3 association with apoptosis is unknown. In addition, the relationship between quercetin as a cardioprotective factor in MI and circular RNA-dependent regulatory pathways has not yet been elucidated. MI was induced in Wistar rats using the left anterior descending artery (LAD) ligation method. One day after surgery, quercetin (30 mg/kg) was injected intraperitoneal (IP) every other day for two weeks. The expression of circPAN3 was increased in the MI group (P < 0.05). The increase in circPAN3 was accompanied by a decrease in miR-221 (P < 0.0001), an increase in PTEN (P < 0.0001), and cleaved caspase 3 (P < 0.001). Quercetin effectively reduced the expression of circPAN3 (P < 0.05), PTEN (P < 0.0001), and cleaved caspase 3 (P < 0.001), and increased the expression of miR-221 (P < 0.0001) and the ratio of p-AKT to p-PI3K (P < 0.001). The circPAN3/miR-221/PTEN pathway is an ncRNA-dependent apoptotic pathway in MI cardiac tissue. Quercetin effectively modulated this pathway, resulting in a reduction of cardiac tissue death and improvement in cardiac function after MI. This suggests that the circPAN3/miR-221 axis plays a role in apoptosis in MI, and quercetin can act as a protective candidate by modulating this pathway.

Therapeutic effects of the combination of moderate-intensity endurance training and MitoQ supplementation in rats with isoproterenol-induced myocardial injury: The role of mitochondrial fusion, fission, and mitophagy.

INTRODUCTION: Mitochondrial dysfunction causes myocardial disease. This study investigated the effects of MitoQ alone and in combination with moderate-intensity endurance training (EX) on cardiac function and content and mRNA expression of several proteins involved in mitochondrial quality control in isoproterenol (ISO)-induced heart injuries METHODS: Seven groups of CTL, ISO, ISO-EX, ISO-MitoQ-125, ISO-MitoQ-250, ISO-EX+MitoQ-125, and ISO-EX+MitoQ-250 were assigned. Rats were trained on a treadmill, and the MitoQ groups received MitoQ in drinking water for 8 weeks, starting one week after the induction of heart injury. Arterial pressure and cardiac function indices, mRNA expression, protein content, oxidant and antioxidant markers, fibrosis, and histopathological changes were assessed by physiograph, Real-Time PCR, immunofluorescence, calorimetry, Masson's trichrome, and H&E staining, respectively. RESULTS: The impacts of MitoQ-125, EX+MitoQ-125, and EX+MitoQ-250 on arterial pressure and left ventricular systolic pressure were higher than MitoQ-250 or EX alone. ± dp/dt max were higher in ISO-EX+MitoQ-125 and ISO-EX+MitoQ-250 than ISO-MitoQ-125 and ISO-MitoQ-250 groups, respectively. Histopathological scores and fibrosis decreased in ISO-EX, ISO-MitoQ-125, ISO-EX+MitoQ-125, and ISO-EX+MitoQ-250 groups. The restoration of MFN2, PINK-1, and FIS-1 changes was higher in ISO-EX+MitoQ-125 and ISO-EX+MitoQ-250 than ISO-EX, ISO-MitoQ-125 and ISO-MitoQ-250 groups. The expression of MFN2 and PINK-1 was lower in ISO-MitoQ-125 and ISO-EX+MitoQ-125 than ISO and CTL groups. The expression of FIS-1 in ISO-EX and ISO-EX+MitoQ-250 increased compared to CTL and ISO groups. MDA decreased in ISO-MitoQ-125 and ISO-EX+MitoQ-125 groups. CONCLUSION: Exercise and MitoQ combination have additive effects on cardiac function by modulating cardiac mitochondria quality. This study provided a possible therapy to treat heart injuries.

Interaction of Klotho and sirtuins.

OBJECTIVE: In this article, we review the articles that have reported the interaction between Klotho and sirtuins. RECENT FINDINGS: Sirtuins are a family of histone deacetylase enzymes that are considered to be the main regulators of biological processes. This family is one of the essential factors for postponing aging and increasing the life span of organisms. Sirtuins play a role in regulating the function of various cellular processes such as cellular metabolism, oxidative stress, apoptosis, and inflammation. It has also been shown that various diseases are related to these enzymes. Klotho is an anti-aging protein that exists as a membrane protein as well as a soluble circulating form. The membrane type of this protein acts as a co-receptor of the FGF endocrine family. It has been shown that the Klotho gene is related to age-related diseases, including osteoporosis, coronary artery, brain diseases, diabetes, etc. At the same time, it is difficult to separate the actions of Klotho and endocrine FGFs. Several studies have shown that Klotho and sirtuins interact with each other at different regulatory levels. However, it is necessary to carry out more in-vivo investigations to create new windows towards the treatment or prevention of various diseases.

Sex-related beneficial effects of exercise on cardiac function and rhythm in autistic rats.

BACKGROUND: Cardiovascular diseases are prevalent in autistic patients. As exercise is useful in the treatment of medical conditions, this study aimed to identify the effect of low-intensity endurance exercise (LIEE) and moderate-intensity endurance exercise (MIEE) on cardiovascular events in autistic rats. METHODS: Valproic acid (VPA) was administrated once on gestational day 12.5 to pregnant rats to produce autism-like symptoms in offspring. Thirty-day-old offspring were divided into 12 groups: Male-CTL, Male-VPA, Male-CTL + LIEE, Male-CTL + MIEE, Male-VPA + LIEE, Male-VPA + MIEE, Female-CTL, Female-VPA, Female-CTL + LIEE, Female-CTL + MIEE, Female-VPA + LIEE, and Female-VPA + MIEE. LIEE and MIEE were performed 5 days a week for 30 days. Twenty-four hours after the last exercise session, electrocardiogram and hemodynamic and cardiac function indices were recorded. RESULTS: The results indicated that +dp/dt max and contractility index (CI) decreased in the Female-VPA group compared to the Female-CTL group. LIEE increased these parameters in the Female-VPA + LIEE group. However, MIEE normalized CI in the Male-VPA + MIEE compared to the Male-VPA group. Tau increased in the Female-VPA group compared to the Female-CTL group and it decreased in the Female-VPA + MIEE group compared to the Female-VPA group. LIEE and MIEE recovered the reduction of heart rate and the increase in P, R, and T amplitudes in Male-VPA group. LIEE and MIEE increased heart rate variability in the Male-VPA and Female-VPA groups. CONCLUSIONS: The findings showed that LIEE and MIEE alleviated cardiac dysfunction and disturbances in heart rhythm in the autistic offspring. Exercise may be recommended as a routine program for autistic patients to prevent and treat the harmful cardiovascular consequences of autism.

Formulation and Evaluation of the Anti-inflammatory, Anti-oxidative, and Anti-remodelling Effects of the Niosomal Myrtenol on the Lungs of Asthmatic Rats.

Asthma is a common chronic allergic disease that affects a significant percentage of the world's population. Niosomes are nanoparticles consisting of non-ionic surfactants that can be used for drug delivery. This research was designed to investigate the impacts of inhalation of simple and niosomal forms of myrtenol against adverse consequences of asthma in rats. Asthma induction was performed via injection of ovalbumin, followed by its inhalation. Niosomes were created by a heating protocol, and their physicochemical features were evaluated. Forty-nine male Wistar rats were allotted into 7 groups (n=7 each): Control (CTL), vacant niosome (VN), Asthma, Asthma+VN, Asthma+SM (simple myrtenol), Asthma+NM (niosomal myrtenol), and Asthma+B (budesonide). Lung remodeling, serum immunoglobulin E (IgE), inflammatory  and cytokines, and antioxidant factors in the lung tissue and bronchoalveolar fluid (BALF), as well as), were evaluated. The results showed that myrtenol-loaded niosomes had appropriate encapsulation efficiency, kinetic release, size, and zeta potential. The thickness of the epithelial cell layer in the lungs, as well as cell infiltration, fibrosis, IgE, reactive oxygen species, interleukin (IL)-6, and tumor nuclear factor alpha (TNF-α) levels, decreased significantly. In contrast, superoxide dismutase and glutathione peroxide activity increased significantly in the serum and BALF of the treated groups. The niosomal form of myrtenol revealed a higher efficacy than simple myrtenol and was similar to budesonide in ameliorating asthma indices.  Inhalation of simple and niosomal forms of myrtenol improved the detrimental changes in the asthmatic lung. The niosomal form induced more prominent anti-asthmatic effects comparable to those of budesonide.

Low Ang-(1-7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19.

It is predictable that the renin-angiotensin-aldosterone and kinin-kallikrein systems are dysregulated in COVID-19 (COV) patients because SARS-CoV-2 requires ACE2 to cause an infection. This study aimed to assess the serum levels of des-arg(9)-bradykinin (DABK) and angiotensin 1-7 (ang-(1-7)) in patients with COV who had the above-mentioned cardiovascular disease risk factors. In a cross-sectional study, 69 COV patients were selected among patients referred to the main referral center for these patients, in Kerman, Iran, and 73 matched control (non-COV) individuals among individuals who participated in the KERCARD cohort study. Serum levels of DABK and ang-(1-7) were measured by ELISA in the groups of CTL (healthy), HTN, DM, OB, COV, COV + HTN, COV + DM, and COV + OB. Ang-(1-7) levels were lower in the COV + HTN group compared to the HTN group. DABK levels were higher in the COV, HTN, and OB groups and in DM + COV subjects compared to their corresponding control group. The levels of ang-(1-7) and DABK were related to HTN and OB, respectively. According to the findings, we can infer that an increase in DABK production in those with the cardiovascular disease risk factors of diabetes, obesity, and hypertension or a decrease in ang-(1-7) in those with hypertension may contribute to the adverse outcomes of SARS-CoV-2 infection.

Treatment for Myocardial Infarction: In Vivo Evaluation of Curcumin-Loaded PEGylated-GQD Nanoparticles.

ABSTRACT: Curcumin (Cur) has been suggested as a complementary treatment for cardiovascular diseases. Its efficiency, however, is modest due to poor biocompatibility. This study examined the effects of curcumin loaded on polyethylene glycol-graphene quantum dots (Cur-PEG-GQDs) on hemodynamic and cardiac function in rats with myocardial infarction (MI). The study groups included control, MI, MI+Cur-3, MI + Cur-7, MI + Cur-15, MI + PEG-GQDs-5, MI + PEG-GQDs-10, MI + Cur-PEG-GQDs-5, and MI + Cur-PEG-GQDs-10. MI was established by left anterior descending artery ligation. Two weeks after intraperitoneal administration of vehicle, Cur, PEG-GQDs, and Cur-PEG-GQDs, blood pressure and heart contractility indices were measured. Triphenyl tetrazolium chloride, colorimetry, and clinical laboratory methods were used to measure the infarct size, the oxidant and antioxidant content, and the kidney and liver function parameters, respectively. In the MI animals, Cur-7, PEG-GQDs-10, Cur-PEG-GQDs-5, and Cur-PEG-GQDs-10 recovered systolic blood pressure, diastolic blood pressure, left ventricular systolic pressure, and ±dp/dt max disturbances and reduced myocardial infarct size, fibrosis, and left ventricular end-diastolic pressure. Curcumin lowered antioxidant markers and elevated 1 oxidant marker in the heart in a dose-dependent manner. Although Cur-PEG-GQDs-5 and Cur-PEG-GQDs-10 reduced curcumin's oxidative stress effects, the superoxide dismutase, glutathione peroxidase, and total antioxidant capacity levels were significantly lower in Cur-PEG-GQDs-5 and Cur-PEG-GQDs-10 groups compared with the MI group. Malondialdehyde levels were lower in Cur-PEG-GQDs-5 and -10 groups compared with the Cur-3, Cur-7, and Cur-15 groups. The glutathione/glutathione disulfide ratio improved in the groups treated by Cur-7, PEG-GQDs-10, Cur-PEG-GQDs-5, and Cur-PEG-GQDs-10. The findings indicated that Cur-PEG-GQDs mitigated MI-induced cardiac dysfunction. However, because of the increase in oxidative stress in the heart, nonclassic mechanisms may be involved in the beneficial effect of Cur-PEG-GQDs on MI-induced cardiac dysfunction.

Changes in serum levels of apelin and nitric oxide in hospitalized patients with COVID-19: association with hypertension, diabetes, obesity, and severity of disease.

BACKGROUND: COVID-19 is an infectious disease currently spreading worldwide. The COVID-19 virus requires angiotensin-converting enzyme 2, an enzyme that plays a vital role in regulating the apelinergic system for entry into target cells. The underlying diseases of hypertension, diabetes mellitus, and obesity are risk factors for the severity of COVID-19 infection. This study aimed to compare the serum levels of apelin and nitric oxide in hospitalized COVID-19 patients and non-COVID-19 subjects with and without the mentioned risk factors. METHODS: Serum samples were taken from 69 COVID-19 patients and 71-matched non-COVID-19 participants enrolled in the Kerman coronary artery disease risk factors cohort study. Study participants were divided into eight groups of control (healthy), hypertension, diabetes mellitus, obesity, COVID-19, COVID-19 + hypertension, COVID-19 + diabetes mellitus, and COVID-19 + obesity (n = 15-20 in each group). Serum apelin and nitrite were measured by the enzyme-linked immunosorbent assay and colorimetric methods, respectively. RESULTS: Hypertensive and obese patients had lower serum apelin compared to the control group. In addition, apelin content was lower in the COVID-19 and COVID-19 + diabetes mellitus groups compared to the non-COVID-19 counterpart groups. Serum apelin levels were positively associated with arterial O2sat. and negatively with the severity of lung involvement. Nitric oxide metabolites were significantly lower in the COVID-19, COVID-19 + diabetes mellitus, and COVID-19 + obesity groups. CONCLUSIONS: The lower apelin and nitric oxide levels in patients with hypertension and obesity or their reduction due to infection with COVID-19 or concomitant COVID-19 + diabetes mellitus may make them vulnerable to experiencing severe diseases.

Effect of an herbal formulation containing Peganum harmala L. and Fraxinus excelsior L. on oxidative stress, memory impairment and withdrawal syndrome induced by morphine.

Background: Traditional Persian medicine has introduced effective remedies in opioid dependence care. One of the most widely used remedies is an herbal formulation containing Peganum harmala L. and Fraxinus excelsior L. (HF). This study investigated the effects of HF to attenuate the withdrawal signs and rewarding effects in morphine-dependent rats.Methods: Forty-nine male Wistar rats were randomly divided into seven groups. The control and vehicle groups received normal saline and sodium carboxymethyl cellulose, respectively. The morphine group received morphine for one week. The single and daily dose of HF groups received morphine similar to the morphine group, and HF (1.4 and 2.8 g/kg) once a day in the daily dose group and only on the last day of the experiment in the single dose of HF group. Finally, the withdrawal signs as well biochemical tests were evaluated. The behavioral parameters were assessed by conditioned place preference (CPP), elevated plus-maze and Y-maze tests. The antioxidant activity of HF was evaluated by measurement of serum contents of malondialdehyde, stable nitric oxide metabolites and total antioxidant capacity (TAC). Moreover, the protein expression of c-fos was assessed by western blotting.Results: Daily treatment with HF significantly reduced the score of CPP behavioral test, all of the withdrawal signs, TAC and the c-fos protein level.Conclusions: The results indicated that HF might be a promising complementary treatment in reducing morphine-induced physical and psychological dependence probably through modulation of c-fos protein expression.

Trends in the Prevalence and Incidence of Opium Abuse and its Association with Coronary Artery Risk Factors in Adult Population in Iran: Findings from Kerman Coronary Artery Disease Risk Factors Study.

Background: The prevalence of opium addiction in Iran is high probably due to the belief that opium has preventive effects against cardiovascular diseases. In the second phase of Kerman coronary artery disease risk factors study, the prevalence, incidence rate, and the association between opium use and other coronary artery disease risk factors (CADRFs) were assessed. Methods: In a cross-sectional study (2014-2018), 9996 inhabitants of Kerman, southeastern Iran, aged 15-80 years were recruited to the study. After taking fasting blood samples, the participants were examined or interviewed for demographic data and CADRFs, including opium use. The participants were categorized into "never", "occasional", and "dependent" users. The association between opium use and CADRFs was assessed with adjusted regression analysis (Stata v.11 software). Results: The overall prevalence of opium consumption was lower than that of five years earlier (P<0.01). The prevalence was currently higher in men than women and decreased in men between the two phases (P<0.001). There was a positive correlation between opium use and depression (P<0.001), anxiety (P<0.05), and a negative association with the level of physical activity (P<0.001). The five-year incident rate of dependent and occasional opium use was 4.2 and 3.9 persons/100 person-years, respectively. The incidence of opium use was higher in diabetic, hypertensive, depressed, anxious, and obese subjects. Conclusion: The study did not demonstrate any protective effects of opium on CADRFs. Considering the higher rate of opium use in subjects with hypertension, diabetes, obesity, and psychological disorders, the health authorities should implement educational programs to warn and correct the unsafe belief.

The crosstalk between long non-coding RNAs and the hedgehog signaling pathway in cancer.

Hedgehog (Hh) is a conserved signaling pathway that is involved in embryo development as well as adult tissue maintenance and repair in invertebrates and vertebrates. Abnormal activation of this pathway in various types of malignant drug- and apoptosis-resistant tumors has made it a therapeutic target against tumorigenesis. Thus, understanding the molecular mechanisms that promote the activation or inhibition of this pathway is critical. Long non-coding RNAs (lncRNAs), a subclass of non-coding RNAs with a length of > 200 nt, affect the expression of Hh signaling components via a variety of transcriptional and post-transcriptional processes. This review focuses on the crosstalk between lncRNAs and the Hh pathway in carcinogenesis, outlines the broad role of Hh-related lncRNAs in tumor progression, and illustrates their clinical diagnostic, prognostic, and therapeutic potential in tumors.

Exercise Training Attenuates Cardiac Vulnerability and Promotes Cardiac Resistance to Isoproterenol-Induced Injury Following Hookah Smoke Inhalation in Male Rats: Role of Klotho and Sirtuins.

Hookah smoking is on the rise around the world. Present study investigated the heart resistance to harmful stress following long-term waterpipe tobacco smoking (WTS) and moderate-intensity exercise training intervention in male Wistar rats. Animals were randomly divided into a non-ischemic heart control group and four ischemic heart groups including ISO (isoproterenol-treated), Ex + ISO (subjected to exercise plus ISO), S + ISO (exposed to hookah smoke plus ISO), and Ex + S + ISO (subjected to exercise along with hookah smoke plus ISO). After eight weeks of training and WTS, heart ischemia induced by isoproterenol injections. Then, cardiac functional indices and some biochemical and histopathological parameters were assessed. WTS + ISO reduced systolic pressure, ± dP/dt max, and contractility indices (P < 0.001 vs. ISO group) and increased end diastolic pressure and Tau index (P < 0.001 vs. ISO) of the left ventricle. Also, WTS + ISO was associated with an increase in Bax protein level and Bax/Bcl-2 ratio (P < 0.05 and P < 001, respectively, vs. ISO group) as apoptotic markers of heart tissue. Hookah smoke significantly decreased SIRT1 (P < 0.05 and P < 0.001, respectively, vs. ISO) and klotho (P < 0.01 and P < 0.001, respectively, vs. ISO) in serum and heart, and SIRT3 and pS9-GSK-3ß (P < 001 and P < 0.05, respectively, vs. ISO) in heart tissue. Combination of exercise with WTS prevented the hookah smoke-induced alterations in apoptotic markers, cardiac functional indices, and SIRT1, SIRT3, klotho, and pS9-GSK-3ß proteins. The findings demonstrated that hookah smoke inhalation intensifies ventricular dysfunction and decreases heart resistance to harmful stresses. Moderate-intensity exercise training attenuated these complications partly through recovering the klotho and sirtuins levels and apoptosis-survival balancing.

Prevalence and incidence of pre-hypertension and hypertension (awareness/control) in Iran: findings from Kerman coronary artery diseases risk factors study 2 (KERCADRS).

Hypertension (HTN) is an important cause of cardiovascular-related morbidity and mortality. The present study was conducted to investigate the prevalence and incidence rate of pre-HTN, diagnosed and undiagnosed HTN, as well as its control and associated factors in adult population in southeast Iran. In a randomized household survey, 9987 participants aged 15-80 years were recruited into the study. HTN was confirmed through examination or using antihypertensive drug(s). Pre-HTN and HTN were defined as 120-139/80-89 and ≥140/90 mmHg for systolic and diastolic BP, respectively. The prevalence of pre-HTN was 28.5%. The prevalence of HTN was 19.2% (13.9% diagnosed and 5.3% undiagnosed). HTN increased with age (from 4% in 15-24 to 67.8% in 75-80 years). Men had higher pre-HTN (35.6% vs. 23.4%) and undiagnosed HTN (7.5% vs. 3.8%) than women. Of those diagnosed, 46.5% had uncontrolled BP, in which, women had better conditions than men (45.6% vs. 47.4%). Obesity, positive family history of HTN, anxiety, and low physical activity were the most significant predictors of HTN. The prevalence of pre-HTN decreased but there was no change in the prevalence of HTN during the last 5 years. The 5-year incidence rate/100 person-years of pre-HTN and HTN was 6.6 and 3.7, respectively. Although there are some promising signs of reducing pre-HTN and slowing HTN rise, currently, almost one-fifth of the adult population suffers from HTN. Given the poor BP control in patients with diagnosed HTN, especially in men, alarms that more effective interventions and strategies are needed to reduce deleterious consequences of HTN.

Beneficial effects of PEGylated graphene quantum dot on arrhythmias induced by myocardial infarction.

Arrhythmias are one of the leading causes of early death following myocardial infarction (MI) and heart failure. Graphene derivatives have emerged as an therapeutic target that have electrical conductivity. The study aimed to evaluate the impacts of polyethylene glycol-graphene quantum dots (GQDs-PEG) on arrhythmias created by MI in the rat. Animals were randomly assigned to five groups of sham, MI, and MI + GQDs-PEG at doses of 5, 10, and 20 mg/kg. MI was induced by the closure of the left anterior descending artery. The day after MI, animals were administered vehicle (phosphate buffered saline) or GQDs-PEG at different doses every other day for 2 weeks. On day 15, electrocardiogram (ECG), mean arterial pressure (MAP), and heart contractility indices were recorded by the PowerLab data acquisition system. GQDs-PEG 20 mg/kg increased contractility and improved the reduction of MAP in the MI group. The prolonged QT and QTc intervals, inverted T wave, and deviated ST segment were modified by GQDs-PEG 10 and 20 mg/kg in rats with MI. The amplitude of the Q wave was also decreased in a dose-dependent manner in the GQDs-PEG-treated rats. The results demonstrated that 2 weeks of treatment with GQDs-PEG normalized ECG abnormalities and improved left ventricular dysfunction in rats with MI.

SIRT1 and Klotho expression in the heart and kidneys of rats with acute and chronic renovascular hypertension.

AIM: To evaluate Klotho and SIRT1 expression in the heart and kidneys of rats with acute and chronic renovascular hypertension. METHODS: Four and sixteen weeks after the induction of renovascular hypertension by clipping the left renal artery, systemic blood pressure, serum angiotensin II level, and the expression of Klotho and SIRT1 proteins and oxidative stress indices in the heart and kidneys were assessed. RESULTS: SIRT1 level was significantly reduced in the ischemic (left) kidney in acute and chronic phases of hypertension. In the heart, it decreased in the acute phase, but increased in the chronic phase. Klotho levels in the heart and kidneys did not change significantly in either hypertension phase. Superoxide dismutase (SOD) activity in the heart significantly decreased, and SOD, total antioxidant capacity, and malondialdehyde in the ischemic kidney significantly increased during the development of hypertension. Serum angiotensin II level significantly increased in the acute phase of hypertension. CONCLUSION: Development of renovascular hypertension was associated with a reduction of SIRT1 expression in the heart and ischemic kidney. As angiotensin II and SIRT1 counteract each other's expression, a SIRT1 reduction in the heart and kidney, along with the influence of systemic/local angiotensin II, seems to be partly responsible for hypertension development. A combination of SIRT1 agonists and angiotensin II antagonists may be considered for use in the treatment of renovascular hypertension.

PEGylated Graphene Quantum Dot Improved Cardiac Function in Rats with Myocardial Infarction: Morphological, Oxidative Stress, and Toxicological Evidences.

INTRODUCTION: The biocompatibility and potential application of graphene-based nanomaterials in biomedicine have been documented. The effects of polyethylene glycol-graphene quantum dots (GQDs-PEG) on cardiac function in rats with myocardial infarction (MI) were examined. METHODS: Wistar rats were randomly assigned to two main groups, each consisting of sham-Veh., MI-Veh., and MI+GQDs-PEG at doses of 5, 10, and 20 mg/kg. MI was induced by the closure of the left anterior descending (LAD) coronary artery. After MI, GQDs-PEG were injected at different doses IP every other day for two weeks. In the end, hemodynamic and heart contractility indices were assessed. The levels of myocardial MDA (malondialdehyde), SOD (superoxide dismutase), GPX (glutathione peroxidase), and TAC (total antioxidant capacity) were measured by the ELISA method. The serum ALP, ALT, AST, creatinine, and urea levels were measured using the photometric method. The infarct size was assessed by TTC staining. RESULTS: GQDs-PEG decreased the infarct size at doses of 10 and 20 mg/kg and recovered the MI-induced reductions of +dp/dt max and -dp/dt max in the study groups. GQDs-PEG normalized systolic blood pressure and left ventricular systolic pressure reduction at the dose of 20 mg/kg in the MI group. Heart SOD, GPX, and TAC increased in the GQDs-PEG 10 and 20 groups. Almost no signs of toxic effects due to GQDs-PEG administration were observed on the liver and kidneys. CONCLUSIONS: The results provided clear evidence that GQDs-PEG improve cardiac performance and hemodynamic parameters in rats with MI by reducing oxidative stress. GQDs-PEG is proposed as a therapeutic target for the treatment of MI.

Klotho and SIRT1 changes from pre-diabetes to diabetes and pre-hypertension to hypertension.

BACKGROUND: Hypertension and diabetes are among the most important risk factors of cardiovascular diseases. Klotho and SIRT1 are known as anti-aging factors with beneficial effects on cardiovascular system. In this study we investigated the serum Klotho and SIRT1 levels in pre-diabetic and pre-hypertensive individuals and then in diabetic and hypertensive patients to see their relationship with these diseases. METHOD: 229 individuals divided into six groups with similar gender and age distribution 1-Control (normal BP and FBS) 2-pre-diabetic (FBS between 100 and 125 mg/dl) 3-diabetic (FBS ≥ 126 mg/dl), 4-pre-hypertensive (SBP 120-139 or DBP 80-89 mm Hg) 5-hypertensive (SBP ≥ 140 or DBP ≥ 90 mm Hg), and 6-patients with combined hypertension/diabetes. Serum levels of Klotho and SIRT1 were measured by ELISA method. RESULTS: Serum Klotho and STRT1 levels decreased in pre-diabetes and returned to normal in diabetic patients. Their concentration increased in pre-hypertension and recovered to normal in hypertension. In the physiologic range of FBS there is a negative correlation between Klotho and SIRT1 with FBS. When pathologic ranges of FBS added to analysis, the negative correlation abolished/U shaped. Also an inverse U shape correlation observed between Klotho and SIRT1 with MAP in the range of normal to hypertensive BP levels. There was an overall positive relationship between the serum levels of Klotho and SIRT1 themselves. CONCLUSION: The serum levels of the anti-aging proteins Klotho and SIRT1 increases or reduces at the onset of the disease, as a compensatory mechanism, but as the disease progresses their level recovers.

The Effect of Waterpipe Tobacco Smoking on Bone Healing Following Femoral Fractures in Male Rats.

Background: Given the increasing use of waterpipe tobacco smoking in the world and its unknown effects on bone healing, this study investigated the repairing of femoral bone fractures in rats exposed to waterpipe tobacco smoking (WTS). Main Methods: This study involved 40 male Wistar rats that were divided into two groups, including the femoral fracture (Fx) and the Fx + WTS groups. Each group was divided into two subgroups that were evaluated for bone healing 28 and 42 days after femoral fracture. After fixing the fractured femur, the healing process was evaluated by radiography, pathological indicators, and a measurement of the blood levels of vascular endothelial growth factor (VEGF), parathyroid hormone (PTH), Ca ++, transforming growth factor-beta (TGF-ß), and insulin-like growth factor 1 (IGF-1). Additionally, the density of VEGF and CD34 in fracture tissue was investigated by immunohistochemistry. Key Findings: Radiographic findings showed that factors related to the earlier stages of bone healing had higher scores in the Fx + WTS28 and 42 subgroups in comparison to the Fx groups. The density of VEGF and CD34 showed that the angiogenesis processes were different in the bone fracture area and callus tissue in the Fx +WTS subgroups. The serum levels of VEGF, TGF-ß, and IGF-1 were significantly lower in the Fx +WTS42 group, and PTH in the Fx +WTS28 group was higher than that in the other groups. Significance: The findings showed the disturbance and delay in the femoral fracture union in rats exposed to hookah smoke. This is partly due to the reduction of molecular stimuli of bone synthesis and the attenuation of quantitative angiogenesis.

Involvement of Sirtuins and Klotho in Cardioprotective Effects of Exercise Training Against Waterpipe Tobacco Smoking-Induced Heart Dysfunction.

Despite its negative effect on the cardiovascular system, waterpipe smoking (WPS) is currently popular worldwide, especially among youth. This study investigated the effects of moderate endurance exercise on heart function of rats exposed to WPS and its possible mechanism. The animals were randomly divided into four groups: control group (CTL), the exercise group (Ex) which trained for 8 weeks, the waterpipe tobacco smoking group (S) exposed to smoke inhalation (30 min per day, 5 days each week, for 8 weeks), and the group that did exercise training and received waterpipe tobacco smoke inhalation together (Ex + S). One day after the last session of Ex and WPS, cardiac pressures and functional indices were recorded and calculated. The levels of SIRT1, SIRT3, Klotho, Bax, and Bcl-2 in the serum and heart, the expression of phosphorylated GSK3ß of heart tissue, and cardiac histopathological changes were assessed. WPS reduced systolic pressure, +dP/dt max, -dP/dt max, and heart contractility indices (P < 0.001 vs. CTL) and increased cardiac tissue lesions (P < 0.05 vs. CTL) and end diastolic pressure and Tau index (P < 0.001 vs. CTL) of the left ventricle. Exercise training normalized the left ventricular end diastolic pressure, +dP/dt max, and contractility index. Also, exercise improved the levels of SIRT1, SIRT3, Klotho, and Bcl-2 and reduced Bax level in the heart. The findings showed that WPS causes left ventricular dysfunction. Moderate exercise prevented WPS-induced heart dysfunction partly through its anti-apoptotic features and activation of the sirtuins and Klotho pathways.

The effects of methanolic extract of Glycyrrhiza glabra on the prevention and treatment of bleomycin-induced pulmonary fibrosis in rat: experimental study.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by dyspnea and progressive loss of lung function. In this study, the preventive and therapeutic effects of methanolic extract of Glycyrrhiza glabra on pulmonary fibrosis were investigated. Pulmonary fibrosis was induced by administration of bleomycin (BLM) into the left lung of rats. Methyl-prednisolone (M-pred, 4 mg/kg) and methanolic extract of G. glabra (500 mg/kg) were injected intraperitoneally from the 1st to 14th days in the preventive group and from the 14th to 28th days in the therapeutic group once every day. Pulmonary inflammatory and fibrotic indices were evaluated by hematoxylin and eosin (H&E) and Masson's trichrome, respectively. The level of hydroxyproline as an index of pulmonary fibrosis and malondialdehyde (MDA) as an oxidative stress biomarker and catalase were measured by the related ELISA Kits. Pulmonary inflammatory and fibrotic indices in the G. glabra and M-pred groups significantly reduced compared with BLM group. G. glabra decreased the level of hydroxyproline in pulmonary tissue similar to M-pred. MDA reduced in G. glabra and M-pred groups compared with BLM group. The activity of catalase increased in the G. glabra preventive group. According to the results, G. glabra prevented and treated pulmonary fibrosis and inflammation in rats. Therefore, G. glabra may be suggested for the prevention and treatment of pulmonary fibrosis and inflammation.