Set7 Deletion Prevents Glucose Intolerance and Improves the Recovery of Cardiac Function After Ischemia and Reperfusion in Obese Female Mice.

BACKGROUND/AIMS: An obesogenic diet (high fat and sugar, low fiber) is associated with an increased risk for metabolic and cardiovascular disorders. Previous studies have demonstrated that epigenetic changes can modify gene transcription and protein function, playing a key role in the development of several diseases. The methyltransferase Set7 methylates histone and non-histone proteins, influencing diverse biological and pathological processes. However, the functional role of Set7 in obesity-associated metabolic and cardiovascular complications is unknown. METHODS: Wild type and Set7 knockout female mice were fed a normal diet or an obesogenic diet for 12 weeks. Body weight gain and glucose tolerance were measured. The 3T3-L1 cells were used to determine the role of Set7 in white adipogenic differentiation. Cardiac morphology and function were evaluated by histology and echocardiography. An ex vivo Langendorff perfusion system was used to model cardiac ischemia/reperfusion (I/R). RESULTS: Here, we report that Set7 protein levels were enhanced in the heart and perigonadal adipose tissue (PAT) of female mice fed an obesogenic diet. Significantly, loss of Set7 prevented obesogenic diet-induced glucose intolerance in female mice although it did not affect the obesogenic diet-induced increase in body weight gain and adiposity in these animals, nor did Set7 inhibition change white adipogenic differentiation in vitro. In addition, loss of Set7 prevented the compromised cardiac functional recovery following ischemia and reperfusion (I/R) injury in obesogenic diet-fed female mice; however, deletion of Set7 did not influence obesogenic diet-induced cardiac hypertrophy nor the hemodynamic and echocardiographic parameters. CONCLUSION: These data indicate that Set7 plays a key role in obesogenic diet-induced glucose intolerance and compromised myocardial functional recovery after I/R in obese female mice.

What do cochrane systematic reviews say about interventions for enuresis in children and adolescents? An overview of systematic reviews.

OBJECTIVE: To conduct an overview of Cochrane systematic reviews about treatment alternatives for children and/or adolescents with enuresis. SOURCES: An overview of Cochrane systematic reviews about interventions for enuresis in children/adolescents was developed between September/2021 and December/2021. The protocol was registered on PROSPERO and the search was conducted only in the Cochrane Library database without any restriction. Reviews involving any type of intervention for the treatment of enuresis in children/adolescents were included. The risk of bias was assessed using Risk of Bias in Systematic Reviews (ROBIS) and the quality of reviews was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR-2). SUMMARY OF THE FINDINGS: Seven systematic reviews were identified. Based on the ROBIS assessment, all reviews were classified as low risk of bias. According to the AMSTAR-2 assessment, the three oldest systematic reviews were rated as critically low quality, one review was moderate quality, and the three most recent systematic reviews were rated as high quality. No difference was shown between alarm and desmopressin for a complete response to therapy after treatment (RR = 1.30; 95%CI: 0.92 to 1.84), but alarm use is related to a lower risk of adverse events (RR = 0.38; 95%CI: 0.20 to 0.71). There is a moderate certainty that the association between imipramine and oxybutynin is better than placebo to reduce the risk of children who do not achieve 14 consecutive dry nights after treatment (RR = 0.43; 95%CI: 0.23 to 0.78). CONCLUSIONS: There is no difference between alarm and desmopressin for enuresis treatment. However, alarm therapy had fewer adverse events than desmopressin. Moreover, combination therapy between imipramine and oxybutynin is better than placebo.

Ion Channel and Structural Remodeling in Obesity-Mediated Atrial Fibrillation.

BACKGROUND: Epidemiological studies have established obesity as an independent risk factor for atrial fibrillation (AF), but the underlying pathophysiological mechanisms remain unclear. Reduced cardiac sodium channel expression is a known causal mechanism in AF. We hypothesized that obesity decreases Nav1.5 expression via enhanced oxidative stress, thus reducing INa, and enhancing susceptibility to AF. METHODS: To elucidate the underlying electrophysiological mechanisms a diet-induced obese mouse model was used. Weight, blood pressure, glucose, F2-isoprostanes, NOX2 (NADPH oxidase 2), and PKC (protein kinase C) were measured in obese mice and compared with lean controls. Invasive electrophysiological, immunohistochemistry, Western blotting, and patch clamping of membrane potentials was performed to evaluate the molecular and electrophysiological phenotype of atrial myocytes. RESULTS: Pacing-induced AF in 100% of diet-induced obese mice versus 25% in controls (P<0.01) with increased AF burden. Cardiac sodium channel expression, INa and atrial action potential duration were reduced and potassium channel expression (Kv1.5) and current (IKur) and F2-isoprostanes, NOX2, and PKC-α/δ expression and atrial fibrosis were significantly increased in diet-induced obese mice as compared with controls. A mitochondrial antioxidant reduced AF burden, restored INa, ICa,L, IKur, action potential duration, and reversed atrial fibrosis in diet-induced obese mice as compared with controls. CONCLUSIONS: Inducible AF in obese mice is mediated, in part, by a combined effect of sodium, potassium, and calcium channel remodeling and atrial fibrosis. Mitochondrial antioxidant therapy abrogated the ion channel and structural remodeling and reversed the obesity-induced AF burden. Our findings have important implications for the management of obesity-mediated AF in patients. Graphic Abstract: A graphic abstract is available for this article.

"Posterior Tibial Nerve" or "Tibial Nerve"? Improving the reporting in health papers.

AIMS: The primary objective of this study is to identify which term is the most appropriate to use according to anatomical nomenclature: "posterior tibial nerve" or "tibial nerve." Furthermore, this paper intends to show how the use of these terms in papers indexed in important health databases is numerous and to describe the anatomical characteristics of such nerve, to improve future scientific publications. METHODS: This is a descriptive study about the importance of standardizing the use of the terms "posterior tibial nerve" and "tibial nerve" and its anatomy. It comprises three phases: the first is a search in the main databases to identify the use of the terms "posterior tibial nerve" and "tibial nerve." The second phase refers to the consultation of international anatomical terminology to identify the most appropriate term to refer to the nerve, while the third phase is related to the study of the anatomy of this nerve. RESULTS: The term "tibial nerve" is more commonly used, but the use of the term "posterior tibial nerve" is still very substantial. According to international anatomical terminology, the correct term is "tibial nerve," which is a branch of the sciatic nerve. CONCLUSIONS: "Tibial nerve" is the term standardized by international anatomical terminology. The use of terms in accordance with Terminologia Anatomica is important to facilitate the process of teaching and learning, as well as to improve the reporting and interpretation of papers regarding health, and the evidence-based clinical practice.

High fat diet reduces the expression of miRNA-29b in heart and increases susceptibility of myocardium to ischemia/reperfusion injury.

Several studies have shown the role of microRNAs (miRNAs) in myocardial dysfunction in response to ischemia/reperfusion (I/R). In this study, we investigated the impact of high fat (HF) diet in the myocardial susceptibility to I/R injury, as well as in the expression of miRNA-29b. Isolated heart experiments using the ex vivo Langendorff perfusion model were used to induce cardiac I/R injury. HF diet-induced cardiac hypertrophy and impaired cardiac functional recovery after I/R. miRNA-29b, which targets Col1, was reduced in the heart of HF diet-fed mice, whereas the cardiac expression of Col1 was increased. In addition, hypoxia-reoxygenation (H/R) reduced the expression of miRNA-29b in cardiomyoblasts cultures. However, the overexpression of miRNA-29b in cardiomyoblasts reduced p53 mRNA levels and H/R injury, suggesting that downregulation of miRNA-29b may be involved in I/R injury. Together, our findings suggest that the reduced expression of miRNA-29b may be involved in the deteriorated cardiac functional recovery following I/R in obese mice.

Sugarcane biopolymer as a guide tube in the regeneration of peripheral nerves in rats / Biopolímero de caña de azúcar como tubo guía en la regeneración de nervios periféricos en ratones

SUMMARY: Peripheral nerve regeneration is a serious clinical problem. The goal of this work was to evaluate comparatively a biopolymer tube of sugarcane with an expanded polyethylene tube as a tube guide in peripheral nerve regeneration. Fourteen male albino Wistar rats were used, separated into three different groups: control (CG), lesion + polyethylene tube (PG) and lesion + sugarcane biopolymer (SBG). At 60 days old, animals from the PG and SBG underwent surgery for tubulization of the sciatic nerve, and 60 days after the injury they were sacrificed for collection of the nerve. In the analysis of the number of nerve fibers, a smaller number was seen in the PG and SBG groups compared to the CG, no difference was seen between the PG and SBG groups (p<0.05). With regard to the number of blood vessels, the SBG group had a larger number than the CG and PG groups (p<0.05). The SBG also presented increase on axonal diameter and G -ratio compared to PG (p<0.05). Taken together these data revealed that biopolymer tube favors a suitable environment for peripheral nerve regeneration.

RESUMEN: La regeneración nerviosa periférica es un problema clínico grave. El objetivo de este trabajo fue evaluar comparativamente un tubo de biopolímero de caña de azúcar con un tubo de polietileno expandido, como guía de tubo en la regeneración de nervios periféricos. Se utilizaron dieciocho ratas Wistar albinas macho, separadas en tres grupos: control (CG), lesión + tubo de polietileno (PG) y lesión + biopolímero de caña de azúcar (SBG). A los 60 días de edad, los animales del PG y SBG fueron sometidos a una cirugía para la tubulización del nervio ciático, y 60 días después de la lesión fueron sacrificados para la recolección del nervio. En el análisis del número de fibras nerviosas, se observó un número menor en los grupos PG y SBG en comparación con el CG; no se observaron diferencias entre los grupos PG y SBG (p <0,05). Con respecto al número de vasos sanguíneos, el grupo SBG tuvo un número mayor que los grupos CG y PG (p <0,05). El SBG también presentó un aumento en el diámetro axonal y la proporción G en comparación con PG (p <0,05). En conjunto, estos datos revelaron que el tubo de biopolímero favorece un entorno adecuado para la regeneración de nervios periféricos.

Cardioprotective effect of thyroid hormone is mediated by AT2 receptor and involves nitric oxide production via Akt activation in mice.

Studies have demonstrated that thyroid hormone (T3) can precondition the heart against ischaemic injury and improve post-ischaemic recovery. This study investigated whether the AT2 receptor (AT2R) is involved in cardioprotection and the potential molecular mechanism responsible for this effect. Hyperthyroidism was induced in male wild-type (WT) and AT2R knockout (KO) mice by administering daily intraperitoneal injections of T3 (7 µg/100 g body weight) for 14 days. The mouse hearts were harvested and perfused with a Krebs-Henseleit solution at a constant flow in a Langendorff set-up. After 30 min of stabilization, the hearts were subjected to global ischaemia for 20 min and reperfused for 45 min. Baseline cardiac function was assessed by measuring four parameters: LVDP (mmHg), heart rate (bpm), + dP/dt and - dP/dt (mmHg/s). After reperfusion, the total protein from cardiac ventricles was obtained, and the Akt signalling pathway and NO production were evaluated. Post-ischaemic functional recovery was significantly greater (p < 0.05) in the T3-treated WT mice compared to the control, demonstrating the cardioprotective effect of T3. This effect was abolished in T3-treated KO mice, demonstrating the physiological relevance of AT2R to the cardioprotective phenotype induced by T3. Akt activation, iNOS expression and NO production increased in cardiac tissue after T3 treatment in the WT animals, but no difference was observed after treatment in the KO mice. This study indicates that AT2R acts as a cardioprotector in the case of hyperthyroidism. Strategies targeting AT2R agonists might improve cardiac function through NO production and suggest potential therapeutic targets for heart diseases.

Maternal hyperthyroidism increases the susceptibility of rat adult offspring to cardiovascular disorders.

Suboptimal intrauterine conditions as changed hormone levels during critical periods of the development are considered an insult and implicate in physiological adaptations which may result in pathological outcomes in later life. This study evaluated the effect of maternal hyperthyroidism (hyper) on cardiac function in adult offspring and the possible involvement of cardiac Renin-Angiotensin System (RAS) in this process. Wistar dams received orally thyroxin (12 mg/L) from gestational day 9 (GD9) until GD18. Adult offspring at postnatal day 90 (PND90) from hyper dams presented increased SBP evaluated by plethysmography and worse recovery after ischemia-reperfusion (I/R), as evidenced by decreased LVDP, +dP/dT and -dP/dT at 25 min of reperfusion and by increased infarct size. Increased cardiac Angiotensin I/II levels and AT1R in hyper offspring were verified. Herein, we provide evidences that maternal hyperthyroidism leads to altered expression of RAS components in adult offspring, which may be correlated with worse recovery of the cardiac performance after ischemic insults and hypertension.

Angiotensin II type 2 receptor (AT2R) is associated with increased tolerance of the hyperthyroid heart to ischemia-reperfusion.

BACKGROUND: Thyroid hormone induces cardiac hypertrophy and preconditions the myocardium against Ischemia/Reperfusion (I/R) injury. Type 2 Angiotensin II receptors (AT2R) are shown to be upregulated in cardiac hypertrophy observed in hyperthyroidism and this receptor has been reported to mediate cardioprotection against ischemic injury. METHODS: The aim of the present study was to evaluate the role of AT2R in the recovery of myocardium after I/R in isolated hearts from T3 treated rats. Male Wistar rats were treated with triiodothyronine (T3; 7 µg/100 g BW/day, i.p.) in the presence or not of a specific AT2R blocker (PD123,319; 10 mg/Kg) for 14 days, while normal rats served as control. After treatment, isolated hearts were perfused in Langendorff mode; after 30 min of stabilization, hearts were subjected to 20 min of zero-flow global ischemia followed by 25 min, 35 min and 45 min of reperfusion. RESULTS: T3 treatment induced cardiac hypertrophy, which was not changed by PD treatment. Post-ischemic recovery of cardiac function was increased in T3-treated hearts after 35 min and 45 min of reperfusion as compared to control and the ischemic contracture was accelerated and intensified. AT2R blockade was able to return the evaluated functional parameters of cardiac performance (LVDP, +dP/dt(máx) and -dP/dt(min)) to the control condition. Furthermore, AT2R blockade prevented the increase in AMPK expression levels induced by T3, suggesting its possible involvement in this process. CONCLUSION: AT2R plays a significant role in T3-induced cardioprotection.