Perspectives on weight control in diabetes - Tirzepatide.

Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist (GIP/GLP-1 RA) improves glycemic control. Besides improvement of glycemic control, tirzepatide treatment is associated with significantly more weight loss as compared to potent selective GLP-1 receptor agonists as well as other beneficial changes in cardio-metabolic parameters, such as reduced fat mass, blood pressure, improved insulin sensitivity, lipoprotein concentrations, and circulating metabolic profile in individuals with type 2 diabetes (T2D). Some of these changes are partially associated with weight reduction. We review here the putative mechanisms of GIP receptor agonism contributing to GLP-1 receptor agonism-induced weight loss and respective findings with GIP/GLP-1 RAs, including tirzepatide in T2D preclinical models and clinical studies. Subsequently, we summarize the clinical data on weight loss and related non-glycemic metabolic changes of tirzepatide in T2D. These findings suggest that the robust weight loss and associated changes are important contributors to the clinical profile of tirzepatide for the treatment of T2D diabetes and serve as the basis for further investigations including clinical outcomes.

Paclitaxel Protects against Isoproterenol-Induced Damage in Rat Myocardium: Its Heme-Oxygenase Mediated Role in Cardiovascular Research.

(1) Background: In cardiovascular applications, paclitaxel inhibits smooth muscle cell proliferation and migration and significantly reduces the occurrence of restenosis and target lesion revascularization. However, the cellular effects of paclitaxel in the myocardium are not well understood; (2) Methods: Wistar rats were divided into four groups: control (CTRL), isoproterenol (ISO) treated (1 mg/kg) and two groups treated with paclitaxel (PAC), which was administrated (10 mg/kg/day) for 5 days by gavage/per os alone or in combination (ISO + PAC) 3 weeks after ISO treatment. Ventricular tissue was harvested 24 h later for measurements of heme oxygenase (HO-1), reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), NF-κB, TNF-α and myeloperoxidase (MPO); (3) Results: HO-1 protein concentration, HO-1 activity, SOD protein concentration and total glutathione significantly decreased in response to ISO treatment. When PAC was administered in conjunction with ISO, HO-1, SOD concentration and total glutathione were not different from control levels. MPO activity, NF-κB concentration and TNF-α protein concentration were significantly increased in the ISO-only group, while the levels of these molecules were restored when PAC was co-administered; (4) Conclusions: Oral administration of PAC can maintain the expression of important antioxidants, anti-inflammatory molecules, HO-1, SOD and GSH, and suppress the production of TNF-α, MPO and NF-κB, which are involved in myocardial damage. The principal component of this cellular defense seems to be the expression of HO-1.

DNA methylation clock DNAmFitAge shows regular exercise is associated with slower aging and systemic adaptation.

DNAmPhenoAge, DNAmGrimAge, and the newly developed DNAmFitAge are DNA methylation (DNAm)-based biomarkers that reflect the individual aging process. Here, we examine the relationship between physical fitness and DNAm-based biomarkers in adults aged 33-88 with a wide range of physical fitness (including athletes with long-term training history). Higher levels of VO2max (ρ = 0.2, p = 6.4E - 4, r = 0.19, p = 1.2E - 3), Jumpmax (p = 0.11, p = 5.5E - 2, r = 0.13, p = 2.8E - 2), Gripmax (ρ = 0.17, p = 3.5E - 3, r = 0.16, p = 5.6E - 3), and HDL levels (ρ = 0.18, p = 1.95E - 3, r = 0.19, p = 1.1E - 3) are associated with better verbal short-term memory. In addition, verbal short-term memory is associated with decelerated aging assessed with the new DNAm biomarker FitAgeAcceleration (ρ: - 0.18, p = 0.0017). DNAmFitAge can distinguish high-fitness individuals from low/medium-fitness individuals better than existing DNAm biomarkers and estimates a younger biological age in the high-fit males and females (1.5 and 2.0 years younger, respectively). Our research shows that regular physical exercise contributes to observable physiological and methylation differences which are beneficial to the aging process. DNAmFitAge has now emerged as a new biological marker of quality of life.

Resveratrol as a Promising Polyphenol in Age-Associated Cardiac Alterations.

According to a widely accepted theory, oxidative stress is considered to be the number one trigger of aging-associated degenerative processes including cardiovascular diseases. In the context of aging-research, resveratrol receives special attention with its surprising number of health benefits. The aim of our study was to examine the anti-inflammatory and antioxidant effects of this dietary polyphenol in aging rat heart. 20-month-old female and male Wistar rats were divided into control (untreated) and resveratrol-treated groups. Resveratrol was administered at a dose of 0.05 mg/ml for 12 weeks dissolved in drinking water, while the control rats received ad libitum water. Cardiac level of reactive oxygen species (ROS), nuclear factor kappa B (NFκB), tumor necrosis factor alpha (TNF-α), and glutathione (GSH) parameters, as well as the activity of myeloperoxidase (MPO) and heme oxygenase (HO) enzymes were detected. Together with the biochemical measurements, hearts were isolated and used for an exposure of ischemic-reperfusion injury via Langendorff perfusion system. 12 week of resveratrol treatment suppressed the age-related inflammatory pathways including the expression of TNF-α, NFκB, and the activity of MPO while intensified the endogenous antioxidant defenses through the induction of GSH and HO system. Presumably, as a result of these processes, the necrotic area of the heart in response to an acute injury was also significantly reduced in the resveratrol-treated groups. Our findings confirmed that resveratrol has cardioprotective effects at several points by counteracting the aging-associated cellular malfunctions in the heart.

Andrological Aspects of Exercise: Moderate Swimming Protects against Isoproterenol Induced Testis and Semen Abnormalities in Rats.

The development and progression of male infertility are closely linked to a sedentary lifestyle; however, its underlying mechanisms are not fully elucidated. Our aim was to assess the protective effects of moderate swimming exercise on the male reproductive system in isoproterenol-treated rats. Male Wistar rats were divided into five groups as follows: (1) non-interventional controls (CTRL), (2) isoproterenol-treated (ISO), (3) pre-treatment swimming training + ISO (PRE + ISO), (4) ISO + post-treatment swimming training (ISO+POST), (5) pre-treatment swimming training + ISO + post-treatment swimming training (PRE + ISO + POST) groups. Testicular oxidative stress was induced by ISO injection (1.0 mg/kg). Rats in the pre- or post-training groups were trained five days a week. At the end of the experimental period, serum testosterone levels, sperms' hyaluronan binding, and total glutathione (GSH) content, as well as myeloperoxidase activity (MPO), TNF alpha and IL6 concentrations in the testis and semen, were measured. Serum testosterone levels, sperms' hyaluronan binding, and GSH content were found to be significantly reduced, while MPO, TNF alpha and IL6 concentrations in the testis and semen were elevated after the ISO treatment compared to the CTRL group. Moderate-intensity swimming exercise effectively alleviated the negative effects of high oxidative stress. Our findings provide the first evidence that moderate-intensity swimming exercise confers sustained protection from isoproterenol-induced adverse effects on testicular inflammation.

Potential Implications of Rimonabant on Age-Related Oxidative Stress and Inflammation.

Over the last decades, growing interest has turned to preventive and therapeutic approaches for achieving successful aging. Oxidative stress and inflammation are fundamental features of cardiovascular diseases; therefore, potential targets of them can improve cardiac outcomes. Our study aimed to examine the involvement of the endocannabinoid system, especially the CB1 receptor blockade, on inflammatory and oxidant/antioxidant processes. Twenty-month-old female and male Wistar rats were divided into rimonabant-treated and aging control (untreated) groups. Rimonabant, a selective CB1 receptor antagonist, was administered at the dose of 1 mg/kg/day intraperitoneally for 2 weeks. Cardiac amounts of ROS, the antioxidant glutathione and superoxide dismutase (SOD), and the activity and concentration of the heme oxygenase (HO) enzyme were detected. Among inflammatory parameters, nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), and myeloperoxidase (MPO) enzyme activity were measured. Two weeks of low dose rimonabant treatment significantly reduced the cardiac ROS via boosting of the antioxidant defense mechanisms as regards the HO system, and the SOD and glutathione content. Consistently, the age-related inflammatory response was alleviated. Rimonabant-treated animals showed significantly decreased NF-κB, TNF-α, and MPO levels. Our findings prove the beneficial involvement of CB1 receptor blocker rimonabant on inflammatory and oxidative damages to the aging heart.

Nicotinic-acid derivative BGP-15 improves diastolic function in a rabbit model of atherosclerotic cardiomyopathy.

BACKGROUND AND PURPOSE: The small molecule BGP-15 has been reported to alleviate symptoms of heart failure and improve muscle function in murine models. Here, we investigated the acute and chronic effects of BGP-15 in a rabbit model of atherosclerotic cardiomyopathy. EXPERIMENTAL APPROACH: Rabbits were maintained on standard chow (control) or atherogenic diet (hypercholesterolemic) for 16 weeks. BGP-15 was administered intravenously (once) or orally (for 16 weeks), to assess acute and chronic effects. Cardiac function was evaluated by echocardiography, endothelium-dependent vasorelaxation was assessed and key molecules in the protein kinase G (PKG) pathway were examined by enzyme-linked immunosorbent assay (ELISA) and western blot. Passive force generation was investigated in skinned cardiomyocytes. KEY RESULTS: Both acute and chronic BGP-15 treatments improved the diastolic performance of the diseased heart. However, vasorelaxation and serum lipid markers were unaffected. Myocardial cyclic guanosine monophosphate (cGMP) levels were elevated in the BGP-15-treated group, along with preserved PKG activity and increased phospholamban Ser16-phosphorylation. PDE5 expression decreased in the BGP-15-treated group and PDE1 was inhibited. Cardiomyocyte passive tension reduced in BGP-15-treated rabbits, the ratio of titin N2BA/N2B isoforms increased and PKG-dependent N2B-titin phosphorylation elevated. CONCLUSIONS AND IMPLICATIONS: BGP-15 treatment improves diastolic function, reduces cardiomyocyte stiffness and restores titin compliance in a rabbit model of atherosclerotic cardiomyopathy by increasing the activity of the cGMP-PKG pathway. As BGP-15 has been proven to be safe, it may be clinically useful in the treatment of diastolic dysfunction.

Investigation of H2S Donor Treatment on Neutrophil Extracellular Traps in Experimental Colitis.

Inflammatory bowel diseases (IBD) are chronic, immune-mediated disorders, which affect the gastrointestinal tract with intermittent ulceration. It is increasingly clear that neutrophil extracellular traps (NETs) seem to have a role in IBD; however, the associated pathogenesis is still not known. Furthermore, several conventional therapies are available against IBD, although these might have side effects. Our current study aimed to investigate the effects of hydrogen sulfide (H2S) treatment on NETs formation and on the expression of inflammatory mediators in experimental rat colitis. To model IBD, 2,4,6-trinitrobenzenesulfonic acid (TNBS) was administered intracolonically (i.c.) to Wistar-Harlan male rats. Animals were treated (2 times/day) with H2S donor Lawesson's reagent per os. Our results showed that H2S treatment significantly decreased the extent of colonic lesions. Furthermore, the expression of members of NETs formation: peptidyl arginine deiminase 4 (PAD4), citrullinated histone H3 (citH3), myeloperoxidase (MPO) and inflammatory regulators, such as nuclear transcription factor-kappa B (NF-κB) and high-mobility group box 1 (HMGB1) were reduced in H2S treated group compared to TNBS. Additionally, H2S donor administration elevated the expression of ubiquitin C-terminal hydroxylase L1 (UCHL-1), a potential anti-inflammatory mediator. Taken together, our results showed that H2S may exert anti-inflammatory effect through the inhibition of NETs formation, which suggests a new therapeutic approach against IBD.

Multiple Applications of Different Exercise Modalities with Rodents.

A large proportion of chronic diseases can be derived from a sedentary lifestyle. Raising physical activity awareness is indispensable, as lack of exercise is the fourth most common cause of death worldwide. Animal models in different research fields serve as important tools in the study of acute or chronic noncommunicable disorders. With the help of animal-based exercise research, exercise-mediated complex antioxidant and inflammatory pathways can be explored, which knowledge can be transferred to human studies. Whereas sustained physical activity has an enormous number of beneficial effects on many organ systems, these animal models are easily applicable in several research areas. This review is aimed at providing an overall picture of scientific research studies using animal models with a focus on different training modalities. Without wishing to be exhaustive, the most commonly used forms of exercise are presented.

Lifestyle-Induced Redox-Sensitive Alterations: Cross-Talk among the RAAS, Antioxidant/Inflammatory Status, and Hypertension.

The development and progression of hypertension are closely linked to an unhealthy lifestyle; however, its underlying mechanisms are not fully elucidated. Our aim was to assess the effects of diet and exercise on the elements of the renin-angiotensin-aldosterone system (RAAS), redox-sensitive parameters, and the expression of the vascular tone regulator endothelial nitric oxide synthase (eNOS). Male control Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive (SHRSP) rats were randomized based on the type of diet (standard chow, high-fat diet: HT, and fructose-enriched diet: HF) and exercise (voluntary wheel-running exercise or lack of exercise). After 12 weeks of experimental period, the concentrations of the RAAS elements, myeloperoxidase (MPO) activity, tumor necrosis factor alpha (TNF-α) concentrations, levels of superoxide dismutase (SOD) and glutathione (GSH), and expressions of extracellular signal-regulated kinase1/2 (ERK1/2) and phosphorylated ERK1/2 as well as eNOS were measured in the cardiac tissue of WKY and SHRSP rats. We found that the RAAS elements were overactivated under hypertension and were further elevated by HT or HF diet, while HT and HF diet enhanced MPO and TNF-α parameters as well as the expression of pERK1/2; SOD, GSH, and eNOS levels were decreased. These changes occurred in WKKY rats and reached the statistically significant level in SHRSP animals. 12 weeks of exercise compensated the adverse effects of HT and HF via alleviating the concentrations of the RAAS elements and inflammatory markers as well as increasing of antioxidants. Our findings prove that SHRSP rats are more vulnerable to lifestyle changes. Both the type of diet and exercise, as a nonpharmacological therapeutic tool, can have a significant impact on the progression of hypertension.

COVID-19 Infection Alters the Microbiome: Elite Athletes and Sedentary Patients Have Similar Bacterial Flora.

Regular exercise can upgrade the efficiency of the immune system and beneficially alter the composition of the gastro-intestinal microbiome. We tested the hypothesis that active athletes have a more diverse microbiome than sedentary subjects, which could provide better protection against COVID-19 during infection. Twenty active competing athletes (CA) (16 male and 4 females of the national first and second leagues), aged 24.15 ± 4.7 years, and 20 sedentary subjects (SED) (15 male and 5 females), aged 27.75 ± 7.5 years, who had been diagnosed as positive for COVID-19 by a PCR test, served as subjects for the study. Fecal samples collected five to eight days after diagnosis and three weeks after a negative COVID-19 PCR test were used for microbiome analysis. Except for two individuals, all subjects reported very mild and/or mild symptoms of COVID-19 and stayed at home under quarantine. Significant differences were not found in the bacterial flora of trained and untrained subjects. On the other hand, during COVID-19 infection, at the phylum level, the relative abundance of Bacteroidetes was elevated during COVID-19 compared to the level measured three weeks after a negative PCR test (p < 0.05) when all subjects were included in the statistical analysis. Since it is known that Bacteroidetes can suppress toll-like receptor 4 and ACE2-dependent signaling, thus enhancing resistance against pro-inflammatory cytokines, it is suggested that Bacteroidetes provide protection against severe COVID-19 infection. There is no difference in the microbiome bacterial flora of trained and untrained subjects during and after a mild level of COVID-19 infection.

Hormone Replacement Therapy and Aging: A Potential Therapeutic Approach for Age-Related Oxidative Stress and Cardiac Remodeling.

Advanced age is an independent risk factor for cardiovascular diseases, which might be further exacerbated by estrogen deficiency. Hormone replacement therapy (HRT) decreases cardiovascular risks and events in postmenopausal women; however, its effects are not fully elucidated in older individuals. Thus, the aim of our study is to examine the impact of HRT on oxidant/antioxidant homeostasis and cardiac remodeling. In our experiment, control (fertile) and aging (~20-month-old) female Wistar rats were used. Aging rats were further divided into estrogen- (E2, 0.1 mg/kg/day per os) or raloxifene- (RAL, 1.0 mg/kg/day per os) treated subgroups. After 2 weeks of treatment, cardiac heme oxygenase (HO) activity, total glutathione (GSH) content, matrix metalloproteinase-2 (MMP-2) activity, and the concentrations of collagen type I and tissue inhibitor of metalloproteinase (TIMP-2), as well as the infarct size, were determined. The aging process significantly decreased the antioxidant HO activity and GSH content, altered the MMP-2/TIMP-2 signaling, and resulted in an excessive collagen accumulation, which culminated in cardiovascular injury. However, 2 weeks of either E2 or RAL treatment enhanced the antioxidant defense mechanisms and attenuated cardiac remodeling related to aging. Our findings clearly show that 2-week-long HRT is a potential intervention to bias successful cardiovascular aging via reducing oxidative damage and cardiovascular dysfunction.

Exercise-mitigated sex-based differences in aging: from genetic alterations to heart performance.

The prevalence of cardiovascular diseases dramatically increases with age; therefore, striving to maintain a physiological heart function is particularly important. Our aim was to study the voluntary exercise-evoked cardioprotective effects in aged male and female rats, from genetic alterations to changes in heart performance. We divided 20-month-old female and male Wistar rats to control and running groups. After the 12-wk-long experimental period, echocardiographic measurements were performed. Afterwards, hearts were either removed for biochemical measurements or mounted into a Langendorff-perfusion system to detect infarct size. The following genes and their proteins were analyzed from heart: catechol-O-methyltransferase (Comt), endothelin-1 (Esm1), Purkinje cell protein-4 (Pcp4), and osteoglycin (Ogn). Recreational exercise caused functional improvements; however, changes were more prominent in males. Cardiac expression of Comt and Ogn was reduced as a result of exercise in aged males, whereas Pcp4 and Esm1 showed a marked overexpression, along with a markedly improved diastolic function. The key result of this study is that exercise enhanced the expression of the Pcp4 gene and protein, a recently described regulator of calcium balance in cardiomyocytes, and suppressed Comt and Ogn gene expression, which has been associated with impaired cardiac function. In addition, as a result of exercise, a significant improvement was observed in the size of infarct elicited by left anterior descending coronary artery occlusion. Our results clearly show that age and sex-dependent changes were both apparent in key proteins linked to cardiovascular physiology. Exercise-moderated fundamental genetic alterations may have contributed to the functional adaptation of the heart.NEW & NOTEWORTHY Voluntary exercise has proved to be an effective therapeutic tool to improve cardiac function in aged rats with clearly visible sex differences. Long-term exercise is associated with decreased Ogn and Comt expression and enhanced presence of Pcp4 and Esm1 genes. Sex-dependent changes were also observed in the expression of the cardiovascular key proteins. Fundamental alterations in gene and protein expression may contribute to the improvement of cardiac performance.

A Potential Involvement of Anandamide in the Modulation of HO/NOS Systems: Women, Menopause, and "Medical Cannabinoids".

Endocannabinoids and their receptors are present in the cardiovascular system; however, their actions under different pathological conditions remain controversial. The aim of our study was to examine the effects of anandamide (AEA) on heme oxygenase (HO) and nitric oxide synthase (NOS) systems in an estrogen-depleted rat model. Sham-operated (SO) and surgically induced estrogen-deficient (OVX) female Wistar rats were used. During a two-week period, a group of OVX rats received 0.1 mg/kg estrogen (E2) per os, while AEA-induced alterations were analyzed after two weeks of AEA treatment at the dose of 1.0 mg/kg. At the end of the experiment, cardiac activity and expression of HO and NOS enzymes, content of cannabinoid 1 receptor, as well as concentrations of transient potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP) were measured. Our results show that estrogen withdrawal caused a significant decrease in both NOS and HO systems, and a similar tendency was observed regarding the TRPV1/CGRP pathway. Two weeks of either AEA or E2 treatment restored the adverse changes; however, the combined administration of these two molecules did not result in a further improvement. In light of the potential relationship between AEA and HO/NOS systems, AEA-induced upregulation of HO/NOS enzymes may be a therapeutic strategy in estrogen-deficient conditions.

Sigma-1 Receptor Engages an Anti-Inflammatory and Antioxidant Feedback Loop Mediated by Peroxiredoxin in Experimental Colitis.

Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition of the gastrointestinal tract. Since the treatment of IBD is still an unresolved issue, we designed our study to investigate the effect of a novel therapeutic target, sigma-1 receptor (σ1R), considering its ability to activate antioxidant molecules. As a model, 2,4,6-trinitrobenzenesulfonic acid (TNBS) was used to induce colitis in Wistar-Harlan male rats. To test the beneficial effects of σ1R, animals were treated intracolonically (i.c.): (1) separately with an agonist (fluvoxamine (FLV)), (2) with an antagonist of the receptor (BD1063), or (3) as a co-treatment. Our results showed that FLV significantly decreased the severity of inflammation and increased the body weight of the animals. On the contrary, simultaneous treatment of FLV with BD1063 diminished the beneficial effects of FLV. Furthermore, FLV significantly enhanced the levels of glutathione (GSH) and peroxiredoxin 1 (PRDX1) and caused a significant reduction in 3-nitrotyrosine (3-NT) levels, the effects of which were abolished by co-treatment with BD1063. Taken together, our results suggest that the activation of σ1R in TNBS-induced colitis through FLV may be a promising therapeutic strategy, and its protective effect seems to involve the antioxidant pathway system.

Lessons on the Sigma-1 Receptor in TNBS-Induced Rat Colitis: Modulation of the UCHL-1, IL-6 Pathway.

Inflammatory Bowel Disease (IBD) is an autoimmune ailment of the gastrointestinal (GI) tract, which is characterized by enhanced activation of proinflammatory cytokines. It is suggested that the sigma-1 receptor (σ1R) confers anti-inflammatory effects. As the exact pathogenesis of IBD is still unknown and treatment options are limited, we aimed to investigate the effects of σ1R in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental colitis. To this end, male Wistar-Harlan rats were used to model colitic inflammation through the administration of TNBS. To investigate the effects of σ1R, Fluvoxamine (FLV, σ1R agonist) and BD1063 (σ1R antagonist) were applied via intracolonic administration to the animals once a day for three days. Our radioligand binding studies indicated the existence of σ1Rs as [3H](+)-pentazocine binding sites, and FLV treatment increased the reduced σ1R maximum binding capacity in TNBS-induced colitis. Furthermore, FLV significantly attenuated the colonic damage, the effect of which was abolished by the administration of BD1063. Additionally, FLV potentially increased the expression of ubiquitin C-terminal hydrolase ligase-1 (UCHL-1) and the levels of endothelial nitric oxide synthase (eNOS), and decreased the levels of interleukin-6 (IL-6) and inducible NOS (iNOS) expression. In summary, our study offers evidence for the anti-inflammatory potential of FLV and σ1R in experimental colitis, and our results present a promising approach to the development of new σ1R-targeted treatment options against IBD.

Distinct Approaches of Raloxifene: Its Far-Reaching Beneficial Effects Implicating the HO-System.

Selective estrogen receptor modulators (SERMs) were discovered in the mid-1900s in connection with estrogen-related pathological conditions. They were developed to antagonize the adverse effects of estrogen and have been shown to be effective against postmenopausal disorders manifested by estrogen deficiency. Raloxifene (RAL), one of the most widely used SERMs, expresses estrogen-like effects on bones, while it is found to be an antagonist on breast and uterus. RAL has multiple beneficial effects throughout the body, including antioxidant and anti-inflammatory properties, because of which it gains particular attention. Additionally, previous studies have revealed that RAL is an efficient modulator of heme-oxygenase (HO) expression. HO, through its general activity, participates in comprehensive cell defense processes, thus the induction of HO by RAL administration indicates a major role in its therapeutic efficacy. In this review, we compile the current knowledge about the overall metabolic, neurocognitive, and cardiovascular effects of RAL involving the cytoprotective HO-system.

The systemic role of SIRT1 in exercise mediated adaptation.

Cellular energy demands are readily changed during physical exercise resulting in adaptive responses by signaling proteins of metabolic processes, including the NAD+ dependent lysine deacetylase SIRT1. Regular exercise results in systemic adaptation that restores the level of SIRT1 in the kidney, liver, and brain in patients with neurodegenerative diseases, and thereby normalizes cellular metabolic processes to attenuate the severity of these diseases. In skeletal muscle, over-expression of SIRT1 results in enhanced numbers of myonuclei improves the repair process after injury and is actively involved in muscle hypertrophy by up-regulating anabolic and downregulating catabolic processes. The present review discusses the different views of SIRT1 dependent deacetylation of PGC-α.

Spotlight on a New Heme Oxygenase Pathway: Testosterone-Induced Shifts in Cardiac Oxidant/Antioxidant Status.

A low testosterone level contributes to the development of oxidative damages; however, the cardiovascular effects of exogenous hormone therapy are not well elucidated. The aim of our work is to study the association of the testosterone level, antioxidant/oxidant system, and anti-inflammatory status related to the heme oxygenase (HO) system. To determine the effects of testosterone, 10-week-old, and 24-month-old sham-operated and castrated male Wistar rats were used. One part of the castrated animals was daily treated with 2.5 mg/kg cyproterone acetate, while the hormone replacement therapy was performed via an i.m. injection of a dose of 8.0 mg testosterone undecanoate/kg/once a week. The plasma testosterone level, the activity of HO and myeloperoxidase (MPO) enzymes; the concentrations of the HO-1, tumor necrosis alpha (TNF-α), and cyclic guanosine monophosphate (cGMP), as well as the total level of glutathione (GSH + GSSG) were determined from the cardiac left ventricle. In accordance with the testosterone values, the aging process and castration resulted in a decrease in antioxidant HO activity, HO-1 and cGMP concentrations and in the level of GSH + GSSG, whereas the inflammatory TNF-α and MPO activity significantly increased. Testosterone therapy was able to restore the physiological values. Our results clearly show that testosterone replacement therapy increases the antioxidant status and mitigates the inflammatory parameters via the modulation of the HO system.

Porcine circovirus type 3 detection in a Hungarian pig farm experiencing reproductive failures.

Porcine circovirus 3 (PCV3) infection has been reported in piglets and sows with porcine dermatitis and nephropathy syndrome, reproductive failure, and cardiac and multisystemic inflammation. Few studies linked PCV3 infection to increased incidence of abortion and weak-born piglets. This is the first report of a detection of PCV3 Hungarian strain in several organs of aborted and weak-born piglets, including the thymus, lymph node, placenta, spleen, kidney and the liver. The tissue tropism of PCV3 in affected litters was analysed using real-time quantitative PCR, and the result showed the highest load of viral DNA in the thymus and lymph nodes. The ORF2 of Hungarian PCV3 strains was 524 nucleotides in length, and the sequence identity to GenBank sequences ranged from 98.5 per cent to 99.2 per cent. The results suggest that PCV3 may have a relevant role in reproductive failure in gilts.