HF Group Research Articles

Microshear bond strength of resin cement to a zirconia-reinforced lithium silicate glass ceramic using different surface treatments

Background: The purpose of this study was to evaluate the effect of different surface treatments on the microshear bond strength (μSBS) of resin cement to zirconia-reinforced lithium silicate ceramic and to compare it with lithium disilicate ceramic. Materials and Methods: In this in vitro study, 80 specimens containing two glass ceramics of IPS e.max press and VITA SUPRINITY were prepared and categorized into four groups according to the surface treatments (n = 10) as Group 1 (C): no treatment (control); Group 2 (HF): etching with 9% hydrofluoric acid (HF) for 90 s followed by silane application; Group 3 (SPH): sandblasting with Al2O3 particles (50 μm), etching with 35% phosphoric acid for 40 s followed by application of silane and adhesive (Clearfil liner bond F); and Group 4 (SB): sandblasting with Al2O3 followed by silanization. Then, a resin cement (Panavia F2) was applied to the prepared ceramic surfaces. All samples were subjected to thermal aging (5000 cycles, 5–55). The μSBS test was evaluated and failure modes were recorded. Data were analyzed using the Shapiro–Wilk, two-way analysis of variance and Tukey's Honest Significant Difference post hoc tests (P < 0.05). Results: IPS e.max press samples revealed significantly higher μSBS values compared to VITA SUPRINITY (P < 0.001), in whole surface treatments. The HF group showed the highest μSBS value, followed by the SPH and SB groups, respectively (P < 0.001). Adhesive failure was recorded as a predominant failure mode. Conclusion: The adhesion performance of IPS e.max press was significantly higher than VITA SUPRINITY. The common surface treatment protocol including HF application followed by silanization was the most effective surface treatment for both glass ceramics.

The Effect of COVID-19 on Long-Term Cardiac Function in Patients With Chronic Heart Failure

Aim To evaluate functional changes in the heart in the long-term following COVID-19 in patients with chronic heart failure (CHF).Material and methods Case reports of 54 patients aged 69.1±9.7 years who had COVID-19 from January 2021 through January 2022 and had been previously diagnosed with NYHA functional class II-III CHF were studied. Two comparison groups were isolated: HF with LV EF >50 % (n=39) and <50 % (n=15). Echocardiography was used to evaluate changes in LV EF and pulmonary artery systolic pressure (PASP) 5-6 months following COVID-19.Results In all CHF patients after COVID-19 at 5.8 months on average, LV EF decreased (median difference, 2.5 %; 95 % confidence interval (CI): 6.99×10-5- 4.99) and PASP increased (median difference, 8 mm Hg; 95 % CI: 4.5-12.9). In the HF group with LV EF <50 %, the decrease in EF was greater than in the group with LV EF >50 % (6.9 and 0.7 %, respectively; p=0.037); furthermore, the CHF phenotype did not influence the change in PASP (p=0.4). The one-factor regression analysis showed that the dynamics of LV EF decrease was significantly influenced by the baseline decrease in LV EF, whereas the change in PASP was influenced by the dynamics of LV EF decrease, presence of dyslipidemia, and statin treatment. Furthermore, the multifactorial analysis showed that prognostically significant factors for long-term changes in LV EF following COVID-19 were male gender (odds ratio (OR), 5.92; 95 % CI: 1.31-26.75; p=0.014), LV EF at baseline <50 % (OR, 0.88; 95 % CI: 0.8-0.96; p<0.001); changes in PASP depended on the presence of dyslipidemia (OR, 0.08; 95 % CI: 0.01-0.84; p=0.018).Conclusion This study showed that COVID-19 in the long term can influence the course of CHF; in this process, HF patients with EF <50 % have progression of systolic dysfunction and PASP, whereas patients with EF >50 % have an isolated increase in PASP.

Peroxisome proliferator-activated receptors-alpha and gamma synergism modulate the gut-adipose tissue axis and mitigate obesity

AimTo evaluate the effects of single PPARα or PPARγ activation, and their synergism (combined PPARα/γ activation) upon the gut-adipose tissue axis, focusing on the endotoxemia and upstream interscapular brown adipose tissue (iBAT) function in high-saturated fat-fed mice. Methods: Male C57BL/6 mice received a control diet (C, 10% lipids) or a high-fat diet (HF, 50% lipids) for 12 weeks. Then, the HF group was divided to receive the treatments for four weeks: HFγ (pioglitazone, 10 mg/kg), HFα (WY-14643, 3.5 mg/kg), and HFα/γ (tesaglitazar, 4 mg/kg). Results: The HF group exhibited overweight, oral glucose intolerance, gut dysbiosis, altered gut permeability, and endotoxemia, culminating in iBAT whitening. The downregulation of LPS-Tlr4 signaling underpinned reduced inflammation and improved lipid metabolism in iBAT in the HFα/γ group, the unique to show normalized body mass and increased energy expenditure. Conclusion: PPARα/γ synergism treated obesity by ameliorating the gut-adipose tissue axis, where restored gut microbiota and permeability controlled endotoxemia and rescued iBAT whitening through favored thermogenesis.

Experience of Using High-Frequency Lung Ventilation during Cardiopulmonary Bypass in Cardiac Surgery

The incidence of various postoperative complications including pulmonary ones is at a high level in a cardiac surgery. The objective: to evaluate the effectiveness of hig h-f requency lung ventilation during cardiopulmonary bypass as a preventive measure for postoperative pulmonary complications compared to lo w-v olume lung ventilation. Subjects and Methods. 60 patients undergoing cradiac surgery were included in the study. In HF Group ( HF ventilation with airway pressure control at the frequency of 30 0/m in, the ratio of duration of inhalation and exhalation is 1:2, mean airway pressure is 8 mbar) and VC Group (lung ventilation during CPB with parameters: tidal volume is 3 m l/k g, respiratory rate is 6/m in, and positive en d-e xpiratory pressure is +5 cm H 2 O). Results. No significant difference in the analysis of the oxygenation index were observed between groups. Frequency of pulmonary atelectasis on chest radiology in postoperative period made 3 (9%) in VC Group and 4 (12%) HF Group ( p = 0.71). The frequency of intraoperative recruiting lung maneuvers was 5 (16%) in VС Group and 6 in HF Group (18%) ( p = 0,75). The duration of postoperative ventilation did not differ between the groups. Conclusion. HF mechanical ventilation during CPB has no significant advantage over lo w-v olume mechanical ventilation. HF mechanical ventilation and lo w-v olume mechanical ventilation has the same protective effect on the oxygenating function of the lungs after CPB .

328 IMPACT OF INTEGRATED CARE WITH ABC PATHWAY IN PATIENTS WITH ATRIAL FIBRILLATION AND HEART FAILURE: DATA FROM MORE THAN 11000 PATIENTS ENROLLED IN A EUROPEAN REGISTRY

Abstract Background and aim Heart failure (HF) is closely associated with atrial fibrillation (AF). The Atrial fibrillation Better Care (ABC) pathway is recommended in guidelines as a holistic or integrated care approach to AF management. However, few data are specifically available on ABC pathway adherence in AF patients with HF, especially according to HF phenotypes. Therefore, we aimed to retrospectively investigate the effect of ABC management in a large contemporary cohort of AF patients with HF and the impact on the clinical outcomes. Methods We analyzed patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. According to the availability of HF status and ejection fraction (EF) values, patients were categorized as follows: i) non-HF; ii) HF EF>40% iii) HF EF≤40%. The primary outcome was a composite outcome of all-cause death and major adverse cardiac events. Results Among the original 11 096 AF patients enrolled, 9175 (82.7%) were included in this analysis (median age 71 years, interquartile range [IQR 63-77], 40.1% were female, with median EF 55% [IQR 45-61%] and median CHA2DS2-VASc 3 [2-4]). In this cohort, 5935 (64.7%) were non-HF patients, and 3240 (35.3%) had HF patients. According to the EF values, 2005 (65%) were categorized as HF EF>40%, and 1235 (35%) were HF EF≤40%. Overall, ABC pathway adherence in HF patients was 23.3% [95% CI: 21.6-25.2], being higher in HF EF≤40% patients (28.0%) and lower in HF EF>40% ones (21.9%). After a median follow-up of 731[IQR 690-748] days, ABC adherence was associated with a lower risk for the composite outcome compared to non-ABC adherent patients in each HF group (HF EF>40%: ABC 15.4% vs no ABC 20.9%; HF EF≤40%: ABC 20.3% vs no ABC 33.9%; both p<0.001). Cox regression analysis showed that ABC adherence was associated with a lower risk of composite outcome in each HF category (HF EF>40%: HR 0.66 [95% CI: 0.46-0.96], p=0.030; HF EF≤40%: HR 0.60 [95% CI: 0.40-0.90], p=0.013). ABC adherence was associated with a consistent risk reduction for the composite outcome across the entire EF spectrum [Figure]. Conclusions In this large contemporary cohort of AF-HF patients, adherence to the ABC pathway was associated with a lower occurrence of the primary outcome, irrespective of baseline EF. ABC pathway is consistently associated with a lower risk for adverse outcomes across the entire spectrum of EF.

Identification of sperm proteins as biomarkers of field fertility in Holstein-Friesian bulls used for artificial insemination.

Despite passing stringent quality control, bulls used in artificial insemination can vary significantly in their fertility, emphasizing the need for reliable markers of sperm quality. This study aimed to identify sperm proteins acting as biomarkers of fertility in 2 different populations of dairy bulls classified based on their field fertility. Semen was collected and cryopreserved from: 54 Holstein bulls located in Ireland, classified according to fertility indexes as low fertility (LF, n = 23), medium fertility (n = 14), or high fertility (HF, n = 17); and 18 Holstein bulls located in Denmark, classified as LF (n = 8) or HF (n = 10). The proteome was measured through liquid chromatography-mass spectrometry and data were analyzed with the R software. Differentially abundant proteins between HF and LF bulls and biomarker proteins were determined through a modified t-test and random forest, respectively, selecting 301 differentially abundant proteins and 34 biomarker proteins. The predictive ability of the 34 biomarkers was evaluated employing support vector machine as the classifier, using their abundance levels in the Irish bulls to train the model and in the Danish bulls for validation. The prediction accuracy was 94.4%, with only one HF bull misclassified, corresponding to the lowest fertility index bull in the HF group. The biomarkers more abundant in sperm of HF bulls enriched axoneme assembly and sperm motility (false discovery rate <0.05), according to functional analysis. In conclusion, a robust model coupled with the application of appropriate bioinformatic tools allowed the identification of functionally relevant sperm proteins predictive of the fertility of Holstein bulls used in artificial insemination.

Effects of Eicosapentaenoic Acid Supplementation in obese Transgenic Mouse Model of Alzheimer’s Disease

AbstractBackgroundAlzheimer’s disease (AD) is a progressive brain disease characterised by cerebral aggregation of amyloid beta (Aβ) plaques. Obesity is a chronic complex disease characterised by excessive fat accumulation, that is associated with systemic and adipose tissue inflammation, and may increase the risk for AD. Eicosapentaenoic acid (EPA) found in fish oil, is an omega‐3 polyunsaturated fatty acid with anti‐obesity and anti‐inflammatory properties. In this study, we propose that EPA supplementation will protect against AD‐associated metabolic dysfunctions in diet‐induced obese mice. We aim to determine the mechanisms mediating EPA effects in obesity‐related metabolic impairments in diet‐induced obese APPswePS1dE9 AD mouse model.MethodWild‐type (WT) and transgenic Alzheimer’s (TG) male and female mice were randomly assigned to either a low‐fat LF (10% kcal fat), a high‐fat (HF, 45% kcal fat), or a HF diet supplemented with 36 g/kg EPA (EPA) for 8 months. Body weights were measured weekly and tissues including adipose tissue were collected at the end of the intervention for analyses of genes involved in inflammation (TNF, fatty acid synthesis (ACACA), fatty acid oxidation (CPT1). Data were analysed by three‐way ANOVA using GraphPad Prism.ResultOverall, TG females gained less weight in HF and EPA groups, compared to male mice (P = 0.0075 and P &lt; 0.0001, respectively). Moreover, TNF was lower in EPA groups compared to HF groups. Significant main effects were observed for sex in TNF, ACACA, and CPT1 (P&lt;0.0001, P=0.0008, and P&lt;0.0001, respectively). Main effects for genotype were observed for ACACA and CPT1 expression (P=0.0497 and P=0.0318, respectively). Main effects for diet (LF vs HF) were observed for TNF, ACACA, and CPT1 (P=&lt;0.0001, P=0.0004, and P=0.0040, respectively). Moreover, significant main effects of HF vs EPA were observed for ACACA (P=0.0497). Interactions in sex x diet (LF vs HF and HF vs EPA) were observed for TNF (P=0.0003 and P=0.0252, respectively), also in sex x diet (LF vs HF) interactions for CPT1 (P=0.0086).ConclusionOur findings showed that EPA counteracted both inflammation and obesity induced by HF diets, especially in female mice. Further analyses are ongoing to determine mechanisms underlying potential benefits of EPA in obesity‐associated AD.

Cysteamine Supplementation In Vitro Remarkably Promoted Rumen Fermentation Efficiency towards Propionate Production via Prevotella Enrichment and Enhancing Antioxidant Capacity.

Cysteamine (CS) is a vital antioxidant product and nutritional regulator that improves the productive performance of animals. A 2 × 4 factorial in vitro experiment was performed to determine the effect of the CS supplementation levels of 0, 20, 40, and 60 mg/g, based on substrate weight, on the ruminal fermentation, antioxidant capacity, and microorganisms of a high-forage substrate (HF, forage:corn meal = 7:3) in the Statistical Analysis System Institute. After 48 h of incubation, the in vitro dry matter disappearance and gas production in the LF group were higher when compared with a low-forage substrate (LF, forge hay:corn meal = 3:7), which was analyzed via the use of the MIXED procedure of the HF group, and these increased linearly with the increasing CS supplementation (p &lt; 0.01). With regard to rumen fermentation, the pH and acetate were lower in the LF group compared to the HF group (p &lt; 0.01). However, the ammonia N, microbial crude protein, total volatile fatty acids (VFA), and propionate in the LF group were greater than those in the HF group (p &lt; 0.05). With the CS supplementation increasing, the pH, ammonia N, acetate, and A:P decreased linearly, while the microbial crude protein, total VFA, and propionate increased linearly (p &lt; 0.01). Greater antioxidant capacity was observed in the LF group, and the increasing CS supplementation linearly increased the superoxide dismutase, catalase, glutathione peroxidase, total antioxidant capacity, glutathione, and glutathione reductase, while it decreased the malondialdehyde (p &lt; 0.05). No difference occurred in the ruminal bacteria alpha diversity with the increasing CS supplementation, but it was higher in the LF group than in the HF group (p &lt; 0.01). Based on the rumen bacterial community, a higher proportion of Bacteroidota, instead of Firmicutes, was in the LF group than in the HF group. Furthermore, increasing the CS supplementation linearly increased the relative abundance of Prevotella, norank_f_F082, and Prevotellaceae_UCG-001 under the two substrates (p &lt; 0.05). Prevotella, norank_f_F082, and Prevotellaceae_UCG-001 were positively correlated with gas production, rumen fermentation, and antioxidant capacity in a Spearman correlation analysis (r &gt; 0.31, p &lt; 0.05). Overall, a CS supplementation of not less than 20 mg/g based on substrate weight enhanced the rumen fermentation and rumen antioxidant capacity of the fermentation system, and it guided the rumen fermentation towards glucogenic propionate by enriching the Prevotella in Bacteroidetes.

Impact of Pre-Existing History of Heart Failure on Patient Profile, Therapeutic Management, and Prognosis in Cardiogenic Shock: Insights from the FRENSHOCK Registry.

There is a large heterogeneity among patients presenting with cardiogenic shock (CS). It is crucial to better apprehend this heterogeneity in order to adapt treatments and improve prognoses in these severe patients. Notably, the presence (or absence) of a pre-existing history of chronic heart failure (CHF) at time of CS onset may be a significant part of this heterogeneity, and data focusing on this aspect are lacking. We aimed to compare CS patients with new-onset HF to those with worsening CHF in the multicenter FRENSHOCK registry. Altogether, 772 CS patients were prospectively included: 433 with a previous history of CHF and 339 without. Worsening CHF patients were older (68 +/- 13.4 vs. 62.7 +/- 16.2, p &lt; 0.001) and had a greater burden of extra-cardiac comorbidities. At admission, acute myocardial infarction was predominantly observed in the new-onset HF group (49.9% vs. 25.6%, p &lt; 0.001). When focusing on hemodynamic parameters, worsening CHF patients showed more congestion and higher ventricular filling pressures. Worsening CHF patients experienced higher in-hospital all-cause mortality (31.3% vs. 24.2%, p = 0.029). Our results emphasize the great heterogeneity of the patients presenting with CS. Worsening CHF patients had higher risk profiles, and this translated to a 30% increase in in-hospital all-cause mortality. The heterogeneity of this population prompts us to better determine the phenotype of CS patients to adapt their management.

Abstract 14602: Does Cancer Treatment Break Your Heart? A Linked Health Data Analysis of Thecharacteristics and Survival of Patients Who Have Developed Cardiovascular Disease Post Cancer Treatment

Background: Cancer treatment induced cardiotoxicity, can be a devastating outcome of cancer therapy. It is possible that a patient can survive cancer but develop cardiovascular disease (CVD). Aim: to determine whether there are differences in the characteristics of cancer patients who received potentially cardiotoxic cancer therapy and subsequently developed CVD and those who did not. Methods: This epidemiological study will comprise a retrospective analysis of de-identified linked health data sets, including the Integrated Activity Collection (ISAAC) of Hospital Separations, South Australian Cancer Registry (SACR), Northern Territory Cancer Registry (NTCR) and mortality (Births Deaths and Marriage Registry Data) and NT Hospital Separation data. The total population will be segregated in two distinct groups namely ‘Cancer with no HF’ and ‘Cancer with HF’ to compare the between group differences by demographic factors and medical history. Results: Of the (n=17,389) patients who received chemotherapy cancer treatment between July 2001-June 2017, 49% (8,530) were diagnosed with HF post cancer treatment( median age at cancer diagnosis 65 years; 58% male); crude mortality was 73% within the HF and cancer group; cause of death within this group was HF related 14%; cancer related 63%; other 22% compared to the non HF and cancer group ( median age at cancer diagnosis 58 years; 53% male) who had a mortality rate of 46%; 6.2% CVD related; 68.8% cancer related and 25% other. Conclusion: After adjusting for age, sex, tumour grade, cancer site and CVD admissions prior to cancer diagnosis patients with CVD and cancer had poorer outcomes.

Abstract 13809: Multiparametric CMR Tissue Characterization Distinguishes Pathological From Physiological Cardiac Hypertrophy and Correlates With CPET Findings

Introduction: Physiological and pathological cardiac hypertrophy differ in terms of mechanisms, phenotypes, and outcomes. We aimed to characterize the cardiac tissue phenotype of athletes and HF patients. Methods: Prospectively enrolled participants underwent CMR and CPET. HF patients (NYHA class II-III) were classified as HFpEF (LVEF&gt;=45%) or HFrEF (LVEF&lt;45%). Results: One-hundred and eighty participants were categorized in four groups: athletes (n=44, 32±12 years), HFpEF (n=47, 61±11 years, H2FPEF score 5±2), HFrEF (n=47, 54±10 years), and healthy controls (n=42, 41±13 years). LVEF was markedly reduced in HFrEF (athletes 65±6%, HFpEF 59±11, HFrEF 29±9, controls 66±4, p&lt;.001). LV mass index (athletes 65±6%, HFpEF 59±11, HFrEF 29±9, controls 66±4, p&lt;.001) and cardiomyocyte mass index (athletes 64±15g/m 2 , HFpEF 66±24, HFrEF 82±36, controls 42±8, p&lt;.001) were greater in athletes and in HF patients (Fig 1A). Athletes and HFpEF patients had concentric LV remodeling, while HFrEF patients showed eccentric remodeling (Fig 1B). Intracellular lifetime of water was longer in athletes and shorter in HFrEF (athletes .17±.07s, HFpEF .15±.05, HFrEF .13±.05, controls .14±.05, p&lt;.001) (Fig 2A). ECV was similarly increased in both HF groups (athletes .28±.04%, HFpEF .31±.05, HFrEF .31±.05, controls .28±.04, p&lt;.001) (Fig 2B). Native T1 (athletes 1175±55ms, HFpEF 1261±61, HFrEF 1274±61, controls 1229±75, p=.01) correlated with CPET maximal oxygen consumption (VO 2 max) in HF patients (r=-.023, p=.048) (athletes 52±10, HFpEF 18±6, HFrEF 17±4, controls 29±9, p&lt;.001). Conclusion: Physiological hypertrophy was characterized by increased cardiomyocyte diameter, normal ECV, and shorter native T1 due to its greater cardiomyocyte volume. Contrastingly, pathological hypertrophy’s longer native T1 was a result of its higher ECV and correlated with VO 2 max in HF. Cardiomyocyte diameter was smaller in HFrEF than in HFpEF.

Abstract 12529: Left Ventricular Gene Expression Heterogeneity in a Mouse Model of Dyssynchronous and Resynchronized Heart Failure

Introduction Cardiac resynchronization therapy improves the prognosis for patients with heart failure and left bundle branch block through cardiac reverse remodeling. The biological mechanisms governing this process remain largely unknown. In a canine model, it has been shown that dyssynchronous heart failure (DHF) induces regional heterogeneity in left ventricular gene expression which is reversed with resynchronization. We developed a mouse model of dyssynchrony and resynchronization and here use this model to test the hypothesis that DHF induces increased intra left ventricular heterogeneity in gene expression that is ameliorated with resynchronized heart failure (RHF). Methods Heart failure was induced in mice through ischemia/reperfusion. All mice were implanted with a custom-made pacemaker. In the synchronous HF (SHF) group the pacemaker was turned off. In the DHF group the mice received right ventricular pacing (RVP) for four weeks. In the RHF group mice received RVP for two weeks, after which the pacemaker was turned off for two weeks. Heart tissue from the septum and lateral left ventricular wall was subjected to RNA sequencing. Results The expression of 1923 genes differed significantly between early- and late activated left ventricular segments in DHF reflecting regional heterogeneity in gene expression, this disparity was not found in SHF or RHF hearts (Figure A). Figure B shows the ten most significantly upregulated gene ontology (GO) pathways in the lateral wall compared to septum in DHF. These pathways were predominantly associated with cell motility and extracellular matrix processing. Conclusions DHF induces a change in gene expression between the left ventricular septum and lateral wall. This difference is absent in SHF and RHF. Our findings support that resynchronization causes a reversal in gene expression from DHF pattern to SHF pattern and may contribute to further understanding of the remodeling process in DHF and how this may be reversed.

Microbiome-Metabolome Analysis of the Immune Microenvironment of the Cecal Contents, Soft Feces, and Hard Feces of Hyplus Rabbits.

The intestinal microbiota and its metabolites play vital roles in host growth, development, and immune regulation. This study analyzed the microbial community distribution and the cytokine and short-chain fatty acid (SCFA) content of cecal contents (Con group), soft feces (SF group), and hard feces (HF group) of 60-day-old Hyplus rabbits and verified the effect of soft feces on the cecal immune microenvironment by coprophagy prevention (CP). The results showed that there were significant differences in the levels of phylum and genus composition, cytokines, and SCFAs among the Con group, SF group, and HF group. The correlation analysis of cytokines and SCFAs with differential microbial communities showed that Muribaculaceae, Ruminococcaceae_UCG-014, Ruminococcaceae_NK4A214_group, and Christensenellaceae_R-7_Group are closely related to cytokines and SCFAs. After CP treatment, the contents of propionic acid, butyric acid, IL-4, and IL-10 in cecum decreased significantly, whereas TNF-α and IL-1β increased significantly. Moreover, the inhibition of coprophagy led to the downregulation of the expression levels of tight junction proteins (Claudin-1, Occludin, and ZO-1) related to intestinal inflammation and intestinal barrier function, and the ring-like structure of ZO-1 was disrupted. In conclusion, coprophagy can not only help rabbits obtain more probiotics and SCFAs but also play an essential role in improving the immune microenvironment of cecum.

Comparison between aerobic exercise training and enalapril treatment as tools to improve diet-induced metabolic-associated fatty liver disease: Effects on endoplasmic reticulum stress markers

AimsEndoplasmic reticulum (ER) stress poses a new pathological mechanism for metabolic-associated fatty liver disease (MAFLD). MAFLD treatment has encompassed renin-angiotensin system (RAS) blockers and aerobic exercise training, but their association with hepatic ER stress is not well known. Therefore, we aimed to compare the effects of hepatic RAS modulation by enalapril and/or aerobic exercise training over ER stress in MAFLD caused by a diet-induced obesity model. Main methodsC57BL/6 mice were fed a standard-chow (CON, n = 10) or a high-fat (HF, n = 40) diet for 8 weeks. HF group was then randomly divided into: HF (n = 10), HF + Enalapril (EN, n = 10), HF + Aerobic exercise training (AET, n = 10), and HF + Enalapril+Aerobic exercise training (EN + AET, n = 10) for 8 more weeks. Body mass (BM) and glucose profile were evaluated. In the liver, ACE and ACE2 activity, morphology, lipid profile, and protein expression of ER stress and metabolic markers were assessed. Key findingsBoth enalapril and aerobic exercise training provided comparable efficacy in improving diet-induced MAFLD through modulation of RAS and ER stress, but the latter was more efficient in improving ER stress, liver damage and metabolism. SignificanceThis is the first study to evaluate pharmacological (enalapril) and non-pharmacological (aerobic exercise training) RAS modulators associated with ER stress in a diet-induced MAFLD model.

Evaluation of lipidomic change in goat sperm after cryopreservation.

The current study aimed to detect the relationship between the spermatozoa cryotolerance and the post-thawed sperm lipidome. Ejaculates from 20 goats, and performed a uniform frozen-thawed procedure in this study. According to the total motility of thawed sperm of goats, semen samples were classified into HF group (High Freezers, n = 8) with >60% total motility and LF group (Low Freezers, n = 8) with < 45% total motility. The lipidomic analysis based on UHPLC-MS/MS was utilized to investigate the relationship between sperm cryotolerance and their lipid metabolites expression. The results showed that the cryotolerance of sperm from different individual goats were in great variation. The total motility of post-thawed sperm in HF group (60.93 ± 2.43%) is significantly higher than that in LF group (34.04 ± 3.41%, P < 0.01). And the post-thawed sperm in HF group exhibited significantly higher plasma membrane (59.06 ± 2.34%) and acrosome integrity (62.93 ± 1.15%) than that in LF group (34.06 ± 4.85%, 44.92 ± 2.19% respectively, P < 0.01). The total of 29 lipid subclasses and 1,133 lipid molecules in the post-thawed goat sperm were identified by lipidomics analysis. The lipid content of thawed sperm in HF group was higher than that in LF group, the lipid profile in HF group was significantly separated from LF group, which indicated that the difference in lipid composition and lipid metabolism mode of sperm between the two groups was existed, especially the expression of phosphatidylcholine and triglyceride molecules. In conclusion, the cryotolerance of sperm from different individual goats were in great variation. Sperm with high cryotolerance may be able to uptake more lipids during cryopreservation. The increase in phosphatidylcholine and triglyceride content of thawed. Sperm may relate to more active lipid anabolic processes.

Offspring NAFLD liver phospholipid profiles are differentially programmed by maternal high-fat diet and maternal one carbon supplement

Little is known if and how maternal diet affects the liver phospholipid profiles that contribute to non-alcoholic fatty liver disease (NAFLD) development in offspring. We examined NAFLD phenotypes in male offspring mice of either maternal normal-fat diet (NF group), maternal high-fat diet (HF group), maternal methionine supplement (H1S group), or complete one-carbon supplement (H2S group) added to the maternal HF diet during gestation and lactation. HF offspring displayed worsened NAFLD phenotypes induced by post-weaning HF diet, however, maternal one-carbon supplement prevented such outcome. HF offspring also showed a distinct phospholipid profile from the offspring exposed to H1S or H2S diet. Whole genome bisulfite sequencing (WGBS) analysis further identified five pathways involved in phospholipid metabolism altered by different maternal diet interventions. Furthermore, differential methylated regions (DMRs) on Prkca, Dgkh, Plcb1 and Dgki were identified comparing between HF and NF offspring; most of these DMRs were recovered in H2S offspring. These methylation pattern changes were associated with gene expression changes: HF diet significantly reduced while H1S and H2S diet recovered their levels. Maternal HF diet disrupted offspring phospholipid profiles contributing to worsened hepatic steatosis. The maternal one-carbon supplement prevented such effects, probably through DNA methylation modification.

Lipid metabolism disorders of hybrid grouper (♀Epinephelus fuscointestinestatus × ♂E. lanceolatu) induced by high-lipid diet

This study investigated the effect of lipid levels on growth, body composition, lipid metabolism enzymes activity and related genes expression in hybrid grouper (♀Epinephelus fuscointestinestatus× ♂E. lanceolatu). Three diets with different lipid levels of 6% (low-lipid feed, LF), 11% (medium-lipid feed, MF) and 16% (high-lipid feed, HF) were designed and each diet was fed to triplicate groups of 30 fish each (6.73 ± 0.00g) for eight weeks. The results revealed the following. 1) The maximum weight gain rate (WGR), specific growth rate (SGR), protein efficiency ratio (PER) and the lowest feed conversion ratio (FCR) values were found in the HF group. There was no significant difference in the survival rate (SR) among the groups (P&amp;gt; 0.05). 2) Condition factor (CF), hepatosomatic index (HSI) and visceralsomatic index (VSI) increased with increasing dietary lipid. 3) Crude lipid content in the whole-body and muscle increased significantly as the dietary lipid level increased (P&amp;lt; 0.05). 4) Principal component analysis of fatty acids showed that sum n-3 polyunsaturated fatty acids (∑n-3PUFA)/sum n-6 polyunsaturated fatty acids (∑n-6PUFA) was significantly higher in the HF group than in the other two groups (P&amp;lt; 0.05). 5) Biochemical serum indexes showed higher triglycerides (TG), total cholesterol (TC), alkaline phosphatase (AKP) and low-density lipoprotein-cholesterol (LDL-C) levels but lower high-density lipoprotein-cholesterol (HDL-C) level in the HF group. 6) Liver lipid metabolism enzymes activity and biochemical indicators showed that fish fed the MF diet had higher lipoprotein lipase (LPL), hepatic lipase (HL) and triglyceride lipase (ATGL) activity but lower fatty acid synthase (FAS) activity and very-low density lipoprotein-cholesterol (VLDL-C) level. 7) The relative expression levels of lipoprotein lipase (lpl), adipocyte-type fatty acid-binding protein (a-fabp), liver-type fatty acid-binding protein (l-fabp), heart-type fatty acid-binding protein (h-fabp) and hormone-sensitive lipase (hsl) genes in the fish liver were higher in the MF group with increasing dietary lipid (P&amp;lt; 0.05), while the fatty acid synthase (fas) gene was expressed at lower relative level (P&amp;lt; 0.05). 8) Histological oil-red sections of the liver showed that fish in the HF group had larger and more hepatic lipid droplets than those fed the other diets. It was concluded that fish fed the HF diet had better growth performance but this diet was not conducive to the progress of lipid metabolism, resulting in lipid accumulation and affecting the quality of the fish. This study provides useful information for the formulation of environmentally friendly and cost-effective diets for hybrid grouper.

Identification of differentially expressed mRNAs and miRNAs in spermatozoa of bulls of varying fertility.

Bulls used in artificial insemination, with apparently normal semen quality, can vary significantly in their field fertility. This study aimed to characterize the transcriptome of spermatozoa from high (HF) and low (LF) fertility bulls at the mRNA and miRNA level in order to identify potential novel markers of fertility. Holstein-Friesian bulls were assigned to either the HF or LF group (n = 10 per group) based on an adjusted national fertility index from a minimum of 500 inseminations. Total RNA was extracted from a pool of frozen-thawed spermatozoa from three different ejaculates per bull, following which mRNA-seq and miRNA-seq were performed. Six mRNAs and 13 miRNAs were found differentially expressed (P < 0.05, FC > 1.5) between HF and LF bulls. Of particular interest, the gene pathways targeted by the 13 differentially expressed miRNAs were related to embryonic development and gene expression regulation. Previous studies reported that disruptions to protamine 1 mRNA (PRM1) had deleterious consequences for sperm chromatin structure and fertilizing ability. Notably, PRM1 exhibited a higher expression in spermatozoa from LF than HF bulls. In contrast, Western Blot analysis revealed a decrease in PRM1 protein abundance for spermatozoa from LF bulls; this was not associated with increased protamine deficiency (measured by the degree of chromatin compaction) or DNA fragmentation, as assessed by flow cytometry analyses. However, protamine deficiency was positively and moderately correlated with the percentage of spermatozoa with DNA fragmentation, irrespective of fertility group. This study has identified potential biomarkers that could be used for improving semen quality assessments of bull fertility.

The DPP4 inhibitor linagliptin exacerbated heart failure due to energy deficiency via downregulation of glucose absorption and utilization in mice

Abstract Background It was reported that glucagon-like peptide-1 has cardio-protective effects, however, the occurrence of heart failure was increased with DPP4 inhibitor in some large clinical trials. Purpose The purpose of the present work was to clarify whether DPP4 inhibitor had any effects on chronic, dilated heart failure and to identify the mechanisms. Methods Heart / Muscle-specific Manganese superoxide dismutase (Mn-SOD)-deficient mice, (H/M-Sod−/−) which exert dilated cardiomyopathy were randomized to receive low dose (1 mg/kg) linagliptin, HF-L group; high dose (10 mg/kg) linagliptin, HF-H group; mixed with food, or normal food, HF group; for eight weeks. Then, evaluation was performed in cardiac function and pathophysiological changes. Result Interestingly, the mice treated with linagliptin treatment exhibited shorter life span and greater heart/body weight ratio. Echocardiographic studies showed decreased contractility in the HF-H group with compared to the HF control group. In Sirius Red staining, severer fibrosis was also observed in the linagliptin groups. HbA1c levels did not change among three groups, however, glycogen content in the liver was significantly decreased in the linagliptin groups. Similarly, indirect calorimetry showed decreased carbohydrate consumption in the HF-H group compared to the HF control group, suggesting worsening of heart failure was due to unavailability of carbohydrates as an energy source. Therefore, we fed a diet containing 33 wt% glucose to the HF-H group as complementary experiments. As a result, adequate glucose supplementation reduced cardiac fibrosis and cardiac function, while worsened life span, HbA1c levels and CHO consumption were not changed. Therefore, we hypothesized that there might be a change in the absorption of glucose in intestine or utilization ability of glucose in body another experiments were performed. 13C, which was released from mice after the oral administration of 13C glucose and measured by respiratory gas analysis, was significantly reduced in HF-H mice. The measurements the amount of 13C in feces revealed increased levels of unabsorbed glucose by linagliptin treatment in HF. In addition, GLUT2, a glucose transporter, in small intestine, was downregulated in the HF-H and the HF-HG groups. On the other hand, the cardiac uptake of Deoxy-D-glucose, 2-[1,2-3H(N)] (3H-2DG), which was injected from mice tail vein, was not different between in the HF-H group and in the HF control group. Taken together, linagliptin treatment may inhibit glucose transport in intestine in HF. Conclusions Linagliptin treatment exacerbated heart failure, resulting in shortened life span, worsened cardiac function, and fibrosis of the myocardium. DPP4 inhibitor may promote the cardiac cachexia and exacerbate heart failure at least, in part, through modification of glucose absorption and utilization. Funding Acknowledgement Type of funding sources: None.

ABC adherence and impact of optimal medical therapy in heart failure patients with atrial fibrillation

Abstract Background Heart failure (HF) has close association with atrial fibrillation (AF). The ESC guideline recommended Atrial fibrillation Better care (ABC) pathway aims to reduce major cardiovascular adverse outcomes with an integrated care approach. Optimal medical treatment (OMT) represents the cornerstone in HF management. Purpose To investigate the variables affecting OMT treatment and its impact, in conjunction with ABC pathway adherence (vs non-adherence, ie.no ABC), in a large contemporary cohort of European AF patients with HF enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. Methods OMT was defined as treatment with Angiotensin-converting-enzyme inhibitors (ACE-i)/ Angiotensin receptor blockers (ARBs) with Beta-Blockers and/or Mineralocorticoid receptor antagonists (MRAs), and compared to non-OMT adherence (“no OMT”). A logistic regression analysis explored factors associated with OMT adherence. We identified three patient groups: (i) HF with no OMT/no ABC; (ii) HF with OMT/no ABC; (iii) HF with OMT/ABC. Primary outcome was a composite outcome of all-cause death and major adverse cardiac events (MACE). Results Among the original 11096 patients enrolled, 9857 (88.8%) were included in this analysis. Among these, 3819 (38.7%) had HF. Compared to non HF patients, those with HF were older, more likely female, had more comorbidities and higher thromboembolic risk. OMT prevalence was 2228/3819 (58.3%), while ABC adherence was 23.3%. On logistic multivariable regression, increasing age, higher BMI and higher frailty index were associated with OMT adherence, while male sex, anemia, renal disease and EHRA II–IV were inversely associated with OMT adherence. According to three HF groups, the rates of composite outcome progressively decreased (HF with no OMT/no ABC 26.4%; HF with OMT/no ABC 24%, HF with OMT/ABC 19%; p&amp;lt;0.001). Kaplan Meier curve showed progressively lower cumulative risk for the composite outcome across the three groups with the lowest risk among HF patients with OMT/ABC (Log-rank: p=0.002) [Figure 1]. Adjusted Cox regression analysis showed that when compared to HF with no OMT/no ABC group, there was a progressively lower risk with OMT and/or ABC adherence (HF with OMT/no ABC: HR 0.81 [95% CI, 0.64–1.02]; HF with OMT/ABC: HR 0.68 [95% CI, 0.5–0.92]). Conclusions After two years of follow-up, in a large contemporary cohort of European AF patients with HF, OMT adherence was suboptimal, being influenced by several clinical factors, determining a low adherence to the ABC pathway. OMT alone showed a non-significant reduction in composite outcome events. Conversely HF patients managed with OMT in the context of ABC pathway adherence showed the best reduction in risk of adverse outcomes. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Since the start of EORP, the following companies have supported the programme: Abbott Vascular Int. (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and Pfizer Alliance (2011–2016), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2011–2017), Edwards (2016–2019), Gedeon Richter Plc. (2014–2017), Menarini Int. Op. (2009–2012), MSD-Merck &amp; Co. (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), SERVIER (2010–2021), and Vifor (2019–2022). - I agree that this information can be anonymised and then used for statistical purposes only