Editorial of Special Issue “Genetics and Molecular Pathogenesis of Non-Ischemic Cardiomyopathies”

This editorial aims to summarize the eight scientific papers published in the Special Issue “Genetics and Molecular Pathogenesis of Non-ischemic Cardiomyopathies”. Cardiomyopathies are primary diseases of the myocardium, and are leading causes of sudden cardiac death (SCD), particularly in athletes and the young. Diagnosis of affected individuals remains challenging, and a resolutive therapy is still lacking, as current treatments can only attenuate the symptoms but not prevent or rescue the phenotype (1). Genetics and genomics along with studies in cellular and animal models are fundamental for delineating the genetic bases of cardiomyopathies and to elucidate the pathogenesis of these diseases. This could greatly improve diagnosis and prognostic evaluation of the affected individuals as well as their family members and lead to the identification of novel targets for more effective treatments. The papers published in this Special Issue discuss several aspects of genetics, genomics and mechanistic studies in the field of primary cardiomyopathie

Knockdown of plakophilin 2 downregulates MIR-184 through CpG hypermethylation and suppression of the E2F1 pathway and leads to enhanced adipogenesis in vitro

Rationale: PKP2, encoding plakophilin 2 (PKP2), is the most common causal gene for arrhythmogenic cardiomyopathy. Objective: To characterize miRNA expression profile in PKP2-deficient cells. Methods and results: Control and PKP2-knockdown HL-1 (HL-1(Pkp2-shRNA)) cells were screened for 750 miRNAs using low-density microfluidic panels. Fifty-nine miRNAs were differentially expressed. MiR-184 was the most downregulated miRNA. Expression of miR-184 in the heart and cardiac myocyte was developmentally downregulated and was low in mature myocytes. MicroRNA-184 was predominantly expressed in cardiac mesenchymal progenitor cells. Knockdown of Pkp2 in cardiac mesenchymal progenitor cells also reduced miR-184 levels. Expression of miR-184 was transcriptionally regulated by the E2F1 pathway, which was suppressed in PKP2-deficient cells. Activation of E2F1, on overexpression of its activator CCND1 (cyclin D1) or knockdown of its inhibitor retinoblastoma 1, partially rescued miR-184 levels. In addition, DNA methyltransferase-1 was recruited to the promoter region of miR-184, and the CpG sites at the upstream region of miR-184 were hypermethylated. Treatment with 5-aza-2'-deoxycytidine, a demethylation agent, and knockdown of DNA methyltransferase-1 partially rescued miR-184 level. Pathway analysis of paired miR-184:mRNA targets identified cell proliferation, differentiation, and death as the main affected biological processes. Knockdown of miR-184 in HL-1 cells and mesenchymal progenitor cells induced and, conversely, its overexpression attenuated adipogenesis. Conclusions: PKP2 deficiency leads to suppression of the E2F1 pathway and hypermethylation of the CpG sites at miR-184 promoter, resulting in downregulation of miR-184 levels. Suppression of miR-184 enhances and its activation attenuates adipogenesis in vitro. Thus, miR-184 contributes to the pathogenesis of adipogenesis in PKP2-deficient cells

Aloe arborescens supplementation in cat diet: Evaluation of effects by in vitro gas production technique

The aim of the present study was to evaluate the effects of Aloe arborescens on organic matter digestibility (OMD), cumulative gas (OMCV) and short chain fatty acids (SCFA) production, using the in vitro gas production technique (IVGPT). Three adult cats were fed with a commercial diet (CP 31.21; EE 16.64% as fed) for 20 days before the collection of their faeces used as inoculum. The same diet, used as substrate, was incubated in vitro supplemented with different amounts (0, 0.7, 1.6 and 3.2%) of lyophilised Aloe arborescens. OMD, OMCV and SCFA significantly decreased with the increase of Aloe addition; an increase of L-lactic acid production was detected, even if pH was within physiological range. A potential prebiotic role of the Aloe arborescens car- bohydrates was hypothesised in cats, but it needs further investigations. As a whole, our results show that IVGPT can represent a useful tool for nutritional evaluation of novel ingredient and/or additive also in cats

Influence of Feeding Linseed on SCD Activity in Grazing Goat Mammary Glands

The effects of linseed feeding on the stearoyl-CoA desaturase (SCD) activity were evaluated on grazing dairy goats divided into two homogeneous groups (C, control, and L, treated) fed the same amount of concentrate which, for group L was supplemented with linseed. Milk yield was unaffected by the treatment. Group L showed significantly higher milk fat (4.10% vs 2.94%, p < 0.01) than group S. Within milk fatty acids, group C showed significantly higher levels of saturated fatty acids and lower values of mono-unsaturated and polyunsaturated fatty acids. In group L, total CLAs were higher than in group S (0.646% vs 0.311%; p < 0.01) mainly because of the differences in CLA cis9 trans 11 (0.623% vs 0.304%; p < 0.01). In treated animals, SCD activity, measured as cis9 C14:1/C14:0, was lower than in the control group, mainly in July and August

Different carbohydrate sources affect swine performance and post-prandial glycaemic response

The type of starch and fibre in the diet affects several parameters, including glycaemic and insulin response, that are involved in pig growth performance. Four experimental diets for growing pigs differing for carbohydrates source (corn, barley, faba bean and pea) were tested. The diets were analysed in vitro to assess the carbohydrates characteristics, and they were administered to 56 crossbreed growing pigs (Landrace × Large White) randomly divided into four groups (mean age of 95 ± 6 days; body weight 80 kg ± 4 days). Clinical examination and average daily gain were performed before recruitment and after 40 days of experiment. The metabolic effects were investigated by blood count and serum biochemical parameters and by the glycaemic and insulin post-prandial response. The study revealed substantial differences among the diets, suggesting that alternative feedstuffs for swine affect several parameters, including glycaemic and insulin response, with no negative effects on growing performance. The Barley group showed the highest daily weight gain (p < .05) associated with the highest glycaemic (p < .05) and insulin response at 1 and 2 h post-prandial (p < .01), suggesting that the barley-based diet can support performance comparable to that of the corn-based diet in growing pig. By contrast, the lowest glycaemia was observed in the Faba bean group (p < .05), confirming the capacity of this legume to modulate post-prandial glucose levels. Moreover, the ability of some ingredients in lowering glucose and insulin response enriches the knowledge on functional nutrients for animal diets and to prevent the incidence of enteric diseases.Highlights The type of starch and fibre used in the diet highly affected some blood parameters, such as glycaemic and insulin responses. The Barley group showed the highest daily weight gain . Lower glycaemia levels were observed in the Faba bean group compared to the Corn one. Alternative protein sources for swine diets can limit the glycaemic and insulin response with no negative effects on growing performance

Nutritional Characterization of Hay Produced in Campania Region: Analysis by the near Infrared Spectroscopy (NIRS) Technology

: Since the dietary characteristics of hays can be very variable, it is of great importance for nutritionists to know their chemical composition in order to formulate adequate rations for the animals. Laboratory analyses are time-consuming and expensive while the Near Infrared Spectroscopy offers several advantages, including obtaining information on feeds nutritional characteristics very quickly and in situ at the farm, thanks to portable NIRS. In this trial, over 400 hay samples collected in the Campania region (Italy) were analyzed with portable NIRS device. The final aim was to analyze the differences in hay quality in different production areas, highlighting the possible factors involved and suggesting possible corrective measures. All the analyzed hays (polyphite, Gramineae and alfalfa) were significantly (p < 0.05) influenced by the area of cultivation/preservation. In particular, the polyphite and Gramineae hays produced in most of the areas of Campania region showed poor nutritional value due to the low protein content and high structural carbohydrate that significantly reduced its digestibility. The use of high-quality forages in the ration represents a pivotal factor to allow the production of high-quality products of animal origin. The use of NIRS seems to be a valuable strategy to select potential treatments that can increase feed digestibility and to avoid long chemical analysis

Diagnosis and Treatment of Obstructive Hypertrophic Cardiomyopathy

Left ventricular outflow obstruction (LVOTO) and diastolic dysfunction are the main pathophysiological characteristics of hypertrophic cardiomyopathy (HCM)LVOTO, may be identified in more than half of HCM patients and represents an important determinant of symptoms and a predictor of worse prognosis. This review aims to clarify the LVOTO mechanism in, diagnosis of, and therapeutic strategies for patients with obstructive HCM