Circadian Influences on Myocardial Ischemia-Reperfusion Injury and Heart Failure.

The impact of circadian rhythms on cardiovascular function and disease development is well established, with numerous studies in genetically modified animals emphasizing the circadian molecular clock's significance in the pathogenesis and pathophysiology of myocardial ischemia and heart failure progression. However, translational preclinical studies targeting the heart's circadian biology are just now emerging and are leading to the development of a novel field of medicine termed circadian medicine. In this review, we explore circadian molecular mechanisms and novel therapies, including (1) intense light, (2) small molecules modulating the circadian mechanism, and (3) chronotherapies such as cardiovascular drugs and meal timings. These promise significant clinical translation in circadian medicine for cardiovascular disease. (4) Additionally, we address the differential functioning of the circadian mechanism in males versus females, emphasizing the consideration of biological sex, gender, and aging in circadian therapies for cardiovascular disease.

Moderate and high-intensity interval training protect against diabetes-induced modulation of hepatic CD86 and CD206 expression associated with the amelioration of insulin resistance and inflammation in rats.

Diabetes Mellitus (DM) can damage the function of metabolic tissues, including the liver. Liver macrophages are the first responders to tissue damage or exercise. We sought to determine whether eight weeks of interval training (HIIT & MIIT) protect against diabetes-induced modulation of hepatic CD86 and CD206 expression associated with the amelioration of insulin resistance and inflammation in rats. Thirty rats were divided into six groups, including a control group, MIIT, HIIT, DM, DM + MIIT, and DM + HIIT (n = 5 in each group). Diabetes was induced using a combination of a high-fat diet (HFD) and STZ. Wistar rats in the exercise groups were subjected to moderate and high-intensity interval training for eight weeks. After sample collection, liver tissue was removed and weighed. Serum levels of TNFα, IL-6, TGFß, and IL-10 were measured by ELISA. Protein expression of the immune markers CD86 and CD206 in liver tissue was determined by immunohistochemical staining. Induction of diabetes increased glycemic indices, insulin resistance, and liver injury enzymes, especially in DM and DM + HIIT groups (p < 0.05). Moreover, diabetic groups showed an increase in liver CD86 protein expression, an increase in TNFα, IL-6, and TGFß serum levels, and a decrease in liver CD206 and serum IL-10 (p < 0.05). Doing exercise while being diabetic, especially MIIT, significantly reversed the aforementioned factors and reduced insulin resistance (p < 0.05), except IL-10). We concluded that performing exercise training specially MIIT by decreasing CD86 and increasing CD206 in the liver, followed by decreasing pro-inflammatory factors (TNFα, IL-6) caused the regulation of liver enzymes and insulin resistance in diabetic rats. Therefore, it seems that exercise training by regulating macrophage markers CD86 and CD206 can reduce damage to the insulin-signaling pathway by reducing pro-inflammatory cytokines.

Effect of natural neosporosis on bull sperm quality.

Neospora is one of the protozoans that can infect the male and female's reproduction system. Despite the existence of N. caninum in the genitalia, its effect on sperm characteristics was not studied yet. Therefore, the aim of this study was to investigate the influence of natural neosporosis on the sperm parameters of bulls. Using 30 bulls with neosporosis diagnosed by modified agglutination test and enzyme-linked immunosorbent assay (ELISA) and 15 healthy bulls, some sperm parameters such as sperm concentration, viability, motility, and morphology were studied and compared. Also, the activity of super oxide dismutase (SOD), glutathione peroxidase (GPX), and malondialdehyde (MDA) level as the biomarker of lipid peroxidation was investigated. Results showed that sperm concentration, viability, and motility were significantly lower in bulls with neosporosis in the present study. There were no significant differences in activities of SOD and MDA level but GPX activity was significantly increased in infected bulls.

Attenuation of heat stress-induced spermatogenesis complications by betaine in mice.

High temperatures can induce oxidative stress, impairment of spermatogenesis, and reduction of sperm quality and quantity concomitant with transient periods of partial or complete infertility in male mammals. Promising beneficial effects of betaine supplementation on the epididymal spermatozoa have been reported in experimental studies; however, its effects on testicular heat stress (HS)-induced impairment have yet to be determined. In the present study, betaine (Bet) was orally administrated (250 mg/kg day) during a 14-day period, before (Bet + HS group) or after (HS + Bet group) induction of testicular HS in 7-9 week-old male mice. HS was induced by testicular immersion in water at 42 °C in stress groups. Epididymal spermatozoa and testes were collected at days 14 and 28 after HS induction in order to analyze sperm characteristics, testicular oxidative status, and histological changes. Our studies showed that HS reduced testicular weight, the quality and quantity of epididymal spermatozoa, and impaired maturation of germinal cells. The levels of MDA, catalase, SOD, and GPX were increased in the testes of HS-induced mice (P < 0.01). Although betaine treatment before and after exposure to HS enhanced antioxidant defense (P < 0.05) and accelerated germinal epithelium regeneration, its effects on the characteristics of epididymal spermatozoa were scarce. On the other hand, in the absence of heat stress, quality and quantity of epididymal spermatozoa were improved following 14 days of betaine consumption. Our study revealed the beneficial effect of betaine on HS-induced complications of spermatogenesis, as well as its potency to improve epididymal spermatozoa in intact mice.

The Aqueous Extract of Portulaca Oleracea Ameliorates Neurobehavioral Dysfunction and Hyperglycemia Related to Streptozotocin-Diabetes Induced in Ovariectomized Rats.

Diabetes mellitus is one of the most common causes of neuropathy. Although antioxidant and antidiabetic effects of the aqueous extract of purslane (Portulaca oleracea) (AEOP) have been demonstrated before by other researchers, we did not find any study that assessed the psychobiological effects of AEOP in diabetes induced animals. Thirty ovariectomized (OVX) female Wistar rats were randomly divided into 3 groups of control, Dia and Dia+AEOP. The latter group was orally treated by 300 mg/kg of AEOP for 35 days. Dia and Dia+AEOP groups were made diabetic by IP injection of 60 mg/kg of streptozotocin (STZ). The psychobiological effects of AEOP were assessed by Morris water maze (MWM), elevated plus maze (EPM), forced swimming test (FST) and tail pinch stressor (TPS). AEOP significantly decreased hyperglycemia (p<0.001). Diabetes significantly decreased their spatial cognitive performance at the training trial as well as the total distance traveled at the probe trial in MWM (p<0.05). All the diabetes related deficits at training trials were improved by AEOP treatment (p<0.05). AEOP treatment not only improved the motor deficit of Dia group in EPM, but also showed anxiolytic effects compared to both control and Dia groups (p<0.05). In the FST, no differences were observed between any groups (p>0.05). Diabetes significantly increased their non-functional masticatory activity in TPS (p≤0.001) while it was improved in Dia+AEOP group. We showed that AEOP has significant anxiolytic effects and it can improve spatial cognitive performance, locomotor deficit and stress in diabetic OVX rats.

Cannabinoid system of the lateral septum in the modulation of anxiety-like behaviors in rats.

BACKGROUNDS: A large body of evidence suggests that the cannabinoid CB1 receptor plays a key role in the regulation of emotional behaviors. The present study was designed to evaluate the effects of CB1 agonist and antagonist on anxiety-like behaviors in the lateral septum (LS) region of the rat brain using elevated plus maze test. METHODS: Rats were anesthetized with ketamine and xylazine and special cannulas were inserted stereotaxically into the LS region. After 1 week of recovery, the effects of intra-LS administration of the CB1 receptor agonist, WIN 55,212-2 and CB1 receptor antagonist, AM251, on %OAT and %OAE were measured. Moreover, the effects of pretreatment with AM251 on the response induced by intra-LS administration of WIN 55,212-2 were also assessed. RESULTS: Intra-LS administration of WIN 55,212-2 (0.001, 0.005 and 0.5µg/rat) decreased the %OAT and %OAE but not locomotor activity, showing an anxiogenic-like response. Intra-LS injection of different doses of AM251 (0.001, 0.01 and 0.1 µg/rat) did not significantly alter the anxiety-like parameters on the plus-maze test. However, intra-LS injections of AM251 (0.01 µg/rat) significantly reversed WIN 55,212-2-induced anxiogenic-like effects. CONCLUSIONS: The results suggest that the cannabinoid system of the lateral septum modulates anxiety-like behavior through CB1 receptor.