Periodically asymmetric responses of deep chlorophyll maximum to light and thermocline in a clear monomictic lake: Insights from monthly and diel scale observations.

Deep chlorophyll maximum (DCM), a chlorophyll peak in the water column, has important implications for biogeochemical cycles, energy flow and water surface algal blooms in deep lakes. However, how an observed periodically asymmetric DCM response to environmental variables remains unclear, limiting our in-depth understanding and effective eco-environmental management of deep lakes. Based on both monthly field investigations in 2021 and diel continuous observations in 2021-2023 in clear, monomictic Lake Fuxian, Southwest China, the temporal dynamics and drivers of DCM were examined and periodic features of DCM were found, with a formation period (FP, February-July) and a weakening period (WP, August-December). On the monthly scale, although DCM dynamics were partly attributed to thermocline structures, the role of light penetration depths varied with period. In the FP, the influence of light on DCM was direct, i.e., increased depth and thickness but decreased magnitude. Differently, the influence of light mainly occurred by affecting thermocline structures in the WP, where water quality was another important driver. On the diel scale, light was a major reason for a thicker and lower (magnitude) DCM during day than at night, and the response of DCM to environmental factors between the FP and WP differed also more during day. This periodically asymmetric response of daytime DCM not only being caused by light but possibly also related to other physical factors such as lake surface water temperature, wind speed and precipitation. Bayesian network modelling suggested that water darkening and stratification intensification may promote a shallower, thinner and larger (magnitude) DCM in both FP and WP, but achieving such changes in DCM requires different light and thermocline thresholds. Our findings provide new information valuable for modelling DCM and for predicting the related surface algal blooms in deep lakes under climate change and eutrophication.

The emerging role of cardiopulmonary exercise testing and cardiac rehabilitation in dilated cardiomyopathy: A mini review.

Cardiovascular mortality is a major health burden worldwide and the number of patients with cardiac diseases is increasing. Dilated cardiomyopathy (DCM) is the most frequent cause for patient visits in cardiac care units and emergency departments. It is commonly misdiagnosed as ischaemic cardiac disease. Middle- and low-income countries rely on pharmacological management as the only treatment option. Most of the patients cannot afford heart transplants or advanced treatment strategies. Most health professionals also do not prescribe cardiac rehabilitation for DCM patients in their routine clinical practice. There is evidence that supervised cardiac rehabilitation is safe and beneficial for DCM patients. In addition to medications, cardiopulmonary exercise testing (CPET) and supervised cardiac rehabilitation, can provide more benefits to the affected population of cardiomyopathies. CPET and cardiac rehabilitation are still novel concepts in countries like Pakistan. The present review aims to provide clinicians with an overview of an evidence-based and innovative perspective. This perspective emphasizes the utilization of the additional benefits of cardiac rehabilitation in the holistic management of DCM patients and the prevention of chronic heart failure.

Special considerations for the stabilization and resuscitation of patients with cardiac disease in the Neonatal Intensive Care Unit.

Effective resuscitation of neonates with congenital heart disease (CHD) depends on comprehensive planning, thorough understanding of physiology, vigilant monitoring, and interdisciplinary collaboration to achieve the best outcomes. Neonatal heart disease can affect cardiac structure, rhythm, or ventricular function, and may be either congenital or acquired. Critical congenital heart disease (CCHD) can result in inadequate pulmonary blood flow, impaired intracardiac mixing, airway obstruction, or insufficient cardiac output. Tailored resuscitation strategies are important as early as the delivery room, where some CHD lesions may cause immediate cardiovascular instability during the transition from fetal to postnatal circulation. Premature infants with CHD are at higher risk due to their small size and the complications associated with prematurity, affecting both CHD management and overall clinical stability. Addressing both cardiac and non-cardiac causes of decompensation requires a precise understanding of each patient's unique physiology and trajectory from delivery through postintervention intensive care.

PAD inhibition downregulates the cellular fibrotic behavior of senescent myofibroblasts derived from dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is characterized by enlarged, weakened heart ventricles due to chronic fibrosis. Dysfunctional senescent myofibroblasts and excessive citrullination have been implicated in fibrotic diseases. Peptidylarginine deiminases (PADs) are involved in the citrullination of ECM proteins. However, their role in regulating the cellular functions of cardiac myofibroblasts in DCM, is not well understood. This study aimed to evaluate the role of PADs in the cellular biology and fibrotic behavior of myofibroblasts in DCM. RESULTS: Aged cardiac myofibroblasts derived from dilated cardiomyopathy (DCM, N=5) and healthy (HCF, N=3) participants (35-60 years), were cultured in TGFB-conditioned medium and treated with an irreversible pan-PAD inhibitor BB-Cl-amidine. Our findings showed that, compared with HCFs, DCM myofibroblasts showed high expression of PAD-2, PAD-3, citrullinated proteins and ECM proteins (vimentin, fibronectin, actin, and b-Tubulin). BB-Cl-amidine-mediated PAD inhibition directly affected the cell biology of DCM myofibroblasts, as shown by the reduced migration and invasion of DCM myofibroblasts. It also augmented the apoptosis by activating caspase-3 and decreased senescence by regulating p-53. PAD inhibition did not affect the citrullination of vimentin or fibronectin; however, it decreased collagen 1 A expression. CONCLUSIONS: This study revealed that elevated PAD expression facilitates cellular processes mainly senescence, migration, and invasion. PAD inhibition resulted in the downregulation of these cellular functions, thereby reducing the fibrotic behavior of DCM myofibroblasts.

Exploring the etiology of dilated cardiomyopathy using Mendelian randomization.

Background: Observational clinical studies suggest an association between dilated cardiomyopathy (DCM) and various factors including titin, cardiac troponin I (CTnI), desmocollin-2, the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, and renal insufficiency. The causal nature of these associations remains uncertain. This study aims to explore these correlations using the Mendelian randomization (MR) approach. Objective: To investigate the etiology of DCM through Mendelian randomization analysis. Methods: Data mining was conducted in genome-wide association study databases, focusing on variant target proteins (titin, CTnI, desmocollin-2), the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, and renal insufficiency, with DCM as the outcome. The analysis employed various regression models, namely, the inverse-variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode methods. Results: The IVW results showed a correlation between titin protein and DCM, identifying titin as a protective factor [OR = 0.856, 95% CI (0.744-0.985), P = 0.030]. CTnI protein correlated with DCM, marking it as a risk factor [OR = 1.204, 95% CI (1.010-1.436), P = 0.040]. Desmocollin-2 also correlated with DCM and was recognized as a risk factor [OR = 1.309, 95% CI (1.085-1.579), P = 0.005]. However, no causal relationship was found between the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, renal insufficiency, and DCM (P > 0.05). The MR-Egger intercept test indicated no pleiotropy (P > 0.05), affirming the effectiveness of Mendelian randomization in causal inference. Conclusion: Titin, CTnI, and desmocollin-2 proteins were identified as independent risk factors for DCM. Contrasting with previous observational studies, no causal relationship was observed between DCM and the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, or renal insufficiency.

Paediatric HeartMate 3™, the Uneventful 22-Month Journey to Transplantation of a 14-Year-Old-Patient-Time for Prolonged LVAD Support in Children?

We report on a 14-year-old patient who was supported for nearly two years with an ic-LVAD and managed to complete his journey to transplantation without a single complication. Although mechanical assist device support is available for children up to 20 kg in body weight, availability is limited to paracorporeal devices. Intracorporal (ic) left ventricular assist devices (LVADs) for infants in the suitable weight class are a viable option as a bridge-to-transplant, where they make up more than 50% of transplant candidates in their category. A teenager with 59 kg body weight was newly diagnosed with DCM and listed for heart transplantation. After initially being on VA-ECMO, an Abbott HeartMate 3 LVAD with postoperative temporary RVAD support was initialised. RV-support was maintained for 10 days. The further postoperative course was uneventful, and he was discharged on day 98. He was seen regularly in the outpatient department and integrated into school routine again, following the extensive training of his classmates and the responsible school staff. After a total of 672 days on support, he was successfully transplanted. There were no unplanned admissions, thrombotic nor bleeding events, as well as no driveline infection, even though the patient participated in sport classes at school.

Cardioprotective effects of polydatin against myocardial injury in HFD/stz and high glucose-induced diabetes via a Caveolin 1-dependent mechanism.

BACKGROUND: Diabetic cardiomyopathy (DCM) is defined as cardiac dysfunction involving changes in structure, function, and metabolism in the absence of coronary artery disease, which eventually developed into heart failure. There is still a lack of effective drugs for the treatment of DCM, while the ameliorative effects of traditional herbs on DCM have been commonly reported. Polydatin (PD) is a glucoside derivative of traditional herbs of resveratrol, which has been shown to ameliorate the pathological development of DCM. However, the cardioprotective effect and mechanism of PD in the improvement of myocardial injury are still unclear. AIM OF STUDY: This study aimed to investigate the cardio-protective role of PD on DCM and reveal the critical effect of Cav1 in PD' regulation of DCM. MATERIALS AND METHODS: The Cav1-/- and Cav1+/+mice and H9C2 cells were used to induce DCM models and then given PD treatment (150 mg/kg) or not. The cardiac functions of all mice were checked via echocardiography, and myocardial histological changes were measured by H&E, periodic acid-schiff (PAS) and Masson staining. The markers expression of heart fibrosis and inflammation, and hypertrophic factors were detected using western blotting. The NF-κB signaling activation was performed by confocal, immunohistochemical, Electrophoretic mobility shift assay (EMSA) and western blotting. RESULTS: Here, we found that PD significantly improved the cardiac function and injury of diabetic Cav1+/+ mice, and enhanced the expression of Cav1 in the cardiac tissues of diabetic Cav1+/+ mice and HG-induced H9C2 cells. Further investigation showed that when Cav1 was knocked down, PD no longer plays the cardioprotective effect and inhibits the NF-κB signaling pathway activation in HFD/stz-treated diabetic mice and HG-induced H9C2 cells. CONCLUSION: These results demonstrated that PD inhibited the hyperglycemia-induced myocardial injury and inflammatory fibrosis of DCM models in vivo and in vitro, and targeting Cav1 may provide a novel understanding the mechanism of the treatment of PD in DCM.

Unveiling the Spectrum of Minor Genes in Cardiomyopathies: A Narrative Review.

Hereditary cardiomyopathies (CMPs), including arrhythmogenic cardiomyopathy (ACM), dilated cardiomyopathy (DCM), and hypertrophic cardiomyopathy (HCM), represent a group of heart disorders that significantly contribute to cardiovascular morbidity and mortality and are often driven by genetic factors. Recent advances in next-generation sequencing (NGS) technology have enabled the identification of rare variants in both well-established and minor genes associated with CMPs. Nowadays, a set of core genes is included in diagnostic panels for ACM, DCM, and HCM. On the other hand, despite their lesser-known status, variants in the minor genes may contribute to disease mechanisms and influence prognosis. This review evaluates the current evidence supporting the involvement of the minor genes in CMPs, considering their potential pathogenicity and clinical significance. A comprehensive analysis of databases, such as ClinGen, ClinVar, and GeneReviews, along with recent literature and diagnostic guidelines provides a thorough overview of the genetic landscape of minor genes in CMPs and offers guidance in clinical practice, evaluating each case individually based on the clinical referral, and insights for future research. Given the increasing knowledge on these less understood genetic factors, future studies are essential to clearly assess their roles, ultimately leading to improved diagnostic precision and therapeutic strategies in hereditary CMPs.

Biallelic NEXN variants and fetal onset dilated cardiomyopathy: two independent case reports and revision of literature.

BACKGROUND: Dilated cardiomyopathy (DCM) is an etiologically heterogeneous group of diseases of the myocardium. With the rapid evolution in laboratory investigations, genetic background is increasingly determined including many genes with variable penetrance and expressivity. Biallelic NEXN variants are rare in humans and associated with poor prognosis: fetal and perinatal death or severe DCMs in infants. CASE PRESENTATION: We describe two male infants with prenatal diagnosis of dilated cardiomyopathy with impaired ventricular contractility. One of the patients showed hydrops and polyhydramnios. Postnatally, a DCM with severely reduced systolic function was confirmed and required medical treatment. In patient 1, Whole Exome Sequencing (WES) revealed a homozygous NEXN variant: c.1156dup (p.Met386fs) while in patient 2 a custom Next Generation Sequencing (NGS) panel revealed the homozygous NEXN variant c.1579_1584delp. (Glu527_Glu528del). These NEXN variants have not been previously described. Unlike the unfavorable prognosis described for biallelic NEXN variants, we observed in both our patients a favorable clinical course over time. CONCLUSION: This report might help to broaden the present knowledge regarding NEXN biallelic variants and their clinical expression. It might be worthy to consider the inclusion of the NEXN gene sequencing in the investigation of pediatric patients with DCM.

Altered Effective Connectivity During Threat Anticipation in Individuals With Alcohol Use Disorder.

BACKGROUND: A developing theory and recent research suggest that heightened reactivity to uncertain stressors or threats may be an important individual difference factor that facilitates excessive drinking as a means of avoidance-based coping and characterizes individuals with current and past alcohol use disorder (AUD). Neuroimaging studies of unpredictable threat processing have repeatedly demonstrated activation of the anterior insula, anteromedial thalamus, and dorsal anterior cingulate cortex. In the current study, we aimed to understand how these 3 regions function as a network during anticipation of unpredictable threat (and predictable threat). METHODS: Participants were 43 adults (ages 21-30) with AUD and 26 healthy control participants. Functional magnetic resonance imaging and dynamic causal modeling were used to study interregional effective connectivities and predictable and unpredictable threat-related modulations thereof within this network. Parametric empirical Bayesian modeling was used to conduct between-group comparisons in effective connectivities. RESULTS: During unpredictable threat trials, the increased projection from the right anteromedial thalamus to the right anterior insula was significantly present only in the AUD group. This directional influence was stronger among individuals who consumed more drinks per week on average. As expected, we found no group differences in modulatory changes to effective connectivities during predictable threat trials. CONCLUSIONS: To our knowledge, this is the first study to examine directional interactions between key frontolimbic regions during anticipation of unpredictable and predictable threat and demonstrate the importance of bottom-up thalamic-insular projections during unpredictable threat processing in AUD. Prospective studies are warranted to determine whether this association is causal.

Anesthetic management and anesthesia-related complications in dogs with a dilated cardiomyopathy phenotype: a retrospective study of 30 dogs (2010-2024).

OBJECTIVE: To describe perioperative anesthetic management in canines with a dilated cardiomyopathy (DCM) phenotype and to compare the frequency of general anesthesia-related complications with a control group of dogs without heart disease. ANIMALS: 30 dogs with DCM phenotype (cases) and 30 dogs without heart disease (controls). METHODS: Dogs presented to a teaching hospital between 2010 and 2024 that were diagnosed with a DCM phenotype via echocardiography were included in this study. Controls were dogs that presented during the same time period and were matched with cases based on their age, breed, and type of procedure; however, no standardization of treatment between the groups was performed. Medical records were reviewed to evaluate the occurrence of anesthetic complications. RESULTS: Of dogs with a DCM phenotype, 2 had overt DCM, 22 had occult DCM, and 6 had equivocal DCM. Dogs with DCM exhibited a lower likelihood of being premedicated with dexmedetomidine or induced with propofol. Conversely, DCM dogs were more likely to be induced with etomidate or midazolam compared to their counterparts without DCM. Dogs with DCM demonstrated an increased likelihood of experiencing cardiac arrhythmias during anesthesia, received comparatively lower volumes of IV fluids, and were more likely to be administered dobutamine during anesthesia. No significant differences were identified in terms of postanesthesia complications or survival rates to discharge. CLINICAL RELEVANCE: Dogs with a DCM phenotype, primarily characterized by asymptomatic presentation, demonstrated comparable perioperative outcomes under general anesthesia when compared to matched controls, though the lack of standardization in anesthetic management limits definitive conclusions.

Titin Cardiomyopathy Associated With Refractory Ventricular Tachycardia: A Case Report.

Cardiomyopathy is defined as structural and functional myocardial abnormality not attributed to ischemic, valvular, hypertensive, or congenital cardiac causes. The main phenotypes of cardiomyopathy include hypertrophic, dilated, non-dilated left ventricular, restrictive, arrhythmogenic right ventricular, Takotsubo, and left ventricular noncompaction cardiomyopathies. A significant proportion of dilated cardiomyopathy (DCM) cases represents patients with genetic mutations, most commonly titin gene truncating variants (TTNtv). It has been shown that TTNtv mutation contributes to the development of certain types of DCM such as alcohol, chemotherapy, and peripartum. We present a case of DCM where genetic workup revealed TTNtv without other contributing factors. The course was complicated by multiple ventricular tachycardias (VTs) refractory to medical management, despite treatment with amiodarone, sotalol, dofetilide, mexiletine, and propranolol. Interestingly, endocardial mapping failed to delineate the substrate of tachycardia. This report underscores the importance of genetic testing in DCM and highlights the potential association of titin cardiomyopathy with refractory VTs, possibly of epicardial origin.

The association between taurine concentrations and dog characteristics, clinical variables, and diet in English cocker spaniels: The Canine taURinE (CURE) project.

BACKGROUND: Occurrence of low blood taurine concentrations (B-TauC) and predisposing factors to taurine deficiency in English Cocker Spaniels (ECS) are incompletely understood. OBJECTIVES: Investigate the occurrence of low B-TauC in a Swedish population of ECS and evaluate the association between B-TauC and dog characteristics, clinical variables, and diet composition. ANIMALS: One-hundred eighty privately owned ECS. METHODS: Dogs were prospectively recruited and underwent physical examination, blood analyses, and echocardiographic and ophthalmic examinations. Dogs with clinical signs of congestive heart failure (CHF) also underwent thoracic radiography. Taurine concentrations were analyzed in plasma (EDTA and heparin) and whole blood. Diets consumed by the dogs at the time of the examination were analyzed for dietary taurine- (D-TauC), cysteine- (D-CysC), and methionine concentrations (D-MetC). RESULTS: Fifty-three of 180 dogs (29%) had low B-TauC, of which 13 (25%) dogs had clinical and radiographic signs of CHF, increased echocardiographic left ventricular (LV) dimensions and volumes, and impaired LV systolic function. Five (9%) dogs with low B-TauC had retinal abnormalities. Dietary MetC, dietary animal protein source (red/white meat), and age were associated with B-TauC in the final multivariable regression model (P < .001, R2 adj = .39). CONCLUSIONS AND CLINICAL IMPORTANCE: Low B-TauC suggests that taurine deficiency may play a role in the development of myocardial failure and CHF in ECS. Low D-MetC and diets with red meat as the animal protein source were associated with low B-TauC. Dogs with B-TauC below the normal reference range were older than dogs with normal concentrations.

Clinical utility of fMRI in evaluating of LSD effect on pain-related brain networks in healthy subjects.

Objective: We aimed to evaluate the effect of Lysergic acid diethylamide (LSD) on the pain neural network (PNN) in healthy subjects using functional magnetic resonance imaging (fMRI). Methods: Twenty healthy volunteers participated in a balanced-order crossover study, receiving intravenous administration of LSD and placebo in two fMRI scanning sessions. Brain regions associated with pain processing were analyzed by amplitude of low-frequency fluctuation (ALFF), independent component analysis (ICA), functional connectivity and dynamic casual modeling (DCM). Results: ALFF analysis demonstrated that LSD effectively relieves pain due to modulation in the neural network associated with pain processing. ICA analysis showed more active voxels in anterior cingulate cortex (ACC), thalamus (THL)-left, THL-right, insula cortex (IC)-right, parietal operculum (PO)-left, PO-right and frontal pole (FP)-right in the placebo session than the LSD session. There were more active voxels in FP-left and IC-left in the LSD session compared to the placebo session. Functional brain connectivity was observed between THL-left and PO-right and between PO-left with FP-left, FP-right and IC-left in the placebo session. In the LSD session, functional connectivity of PO-left with FP-left and FP-right was observed. The effective connectivity between left anterior insula cortex (lAIC)-lAIC, lAIC-dorsolateral prefrontal cortex (dlPFC) and secondary somatosensory cortex (SII)-dlPFC were significantly different. Finally, the correlation between fMRI biomarkers and clinical pain criteria was calculated. Conclusion: This study enhances our understanding of the LSD effect on the architecture and neural behavior of pain in healthy subjects and provides great promise for future research in the field of cognitive science and pharmacology.

Differences in T cell-associated serum markers between ischemic cardiomyopathy and dilated cardiomyopathy.

Background: Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) have similar clinical manifestations but differ in pathogenesis. We aimed to identify T cell-associated serum markers that can be used to distinguish between ICM and DCM. Methods: We identified differentially expressed genes (DEGs) with transcriptome sequencing data in GSE116250, and then conducted enrichment analysis of DEGs in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Protein-protein interaction (PPI) networks were used to analyze the relationship between T cells-related genes and identify hub genes. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect T cell-associated proteins in serum, and receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of these serum markers. Results: Using the limma package and Venn plots, we found that the non-failing donors (NFD) and DCM groups shared many of the same DEGs and DEGs-enriched functions compared to the ICM group, which were involved in T cell activation and differentiation, among other functions. Subsequently, the immune cell score showed no difference between NFD and DCM, but they were significantly different from ICM patients in CD8 T cells CD4 T cells memory resting and activated, T cells follicular helper, and M1 macrophage. After analyzing T cell-associated DEGs, it was found that 4 DEGs encoding secreted proteins were highly expressed in the ICM group compared with the NFD and DCM groups, namely chemokine (C-C motif) ligand 21 (CCL21), interleukin (IL)-1ß, lymphocyte-activation gene 3 (LAG3), and vascular cell adhesion molecule-1 (VCAM-1). Importantly, the serum levels of CCL21, IL-1ß, LAG3, and VCAM-1 in ICM patients were all significantly higher than those in DCM patients. The ROC curves showed that the area under the curve (AUC) values of serum CCL21, IL-1ß, LAG3, and VCAM-1 were 0.775, 0.868, 0.934, and 0.903, respectively. Conclusions: We have identified four T cell-associated serum markers, CCL21, IL-1ß, LAG3, and VCAM-1, as potential diagnostic serum markers that differentiate ICM from DCM.

Roles of distinct nuclear receptors in diabetic cardiomyopathy.

Diabetes mellitus induces a pathophysiological disorder known as diabetic cardiomyopathy and may eventually cause heart failure. Diabetic cardiomyopathy is manifested with systolic and diastolic contractile dysfunction along with alterations in unique cardiomyocyte proteins and diminished cardiomyocyte contraction. Multiple mechanisms contribute to the pathology of diabetic cardiomyopathy, mainly including abnormal insulin metabolism, hyperglycemia, glycotoxicity, cardiac lipotoxicity, endoplasmic reticulum stress, oxidative stress, mitochondrial dysfunction, calcium treatment damage, programmed myocardial cell death, improper Renin-Angiotensin-Aldosterone System activation, maladaptive immune modulation, coronary artery endothelial dysfunction, exocrine dysfunction, etc. There is an urgent need to investigate the exact pathogenesis of diabetic cardiomyopathy and improve the diagnosis and treatment of this disease. The nuclear receptor superfamily comprises a group of transcription factors, such as liver X receptor, retinoid X receptor, retinoic acid-related orphan receptor-α, retinoid receptor, vitamin D receptor, mineralocorticoid receptor, estrogen-related receptor, peroxisome proliferatoractivated receptor, nuclear receptor subfamily 4 group A 1(NR4A1), etc. Various studies have reported that nuclear receptors play a crucial role in cardiovascular diseases. A recently conducted work highlighted the function of the nuclear receptor superfamily in the realm of metabolic diseases and their associated complications. This review summarized the available information on several important nuclear receptors in the pathophysiology of diabetic cardiomyopathy and discussed future perspectives on the application of nuclear receptors as targets for diabetic cardiomyopathy treatment.

Sex-Specific Response to A1BG Loss Results in Female Dilated Cardiomyopathy.

Background: Cardiac disease often manifests differently in terms of frequency and pathology between men and women. However, the mechanisms underlying these differences are not fully understood. The glycoprotein A1BG is necessary for proper cardiac function in females but not males. Despite this, the role of A1BG in the female heart remains poorly studied. Methods: To determine the sex differential function of A1BG, we generated a novel conditional A1bg allele and a novel conditional A1bg Rosa26 knockin allele. Histology, electrocardiography, transcriptional profiling (RNA-seq), transmission electron microscopy, western blot analyses, mass spectrometry, and immunohistochemistry were used to assess cardiac structure and function. Results: The study reveals that the absence of A1BG results in significant cardiac dysfunction in female but not male mice. Gene expression underscores that A1BG plays a critical role in metabolic processes and the integrity of intercalated discs in female cardiomyocytes. This dysfunction may be related to sex-specific A1BG cardiac interactomes and manifests as structural and functional alterations in the left ventricle indicative of dilated cardiomyopathy, thus suggesting a sex-specific requirement for A1BG in cardiac health. Conclusion: The loss of A1BG in cardiomyocytes leads to dilated cardiomyopathy in females, not males.

Diabetic Heart Disease: An Intricate Interplay of a Widespread Metabolic Disorder with the Cardiovascular System.

Diabetes is a chronic medical condition that causes high glycaemic levels, leading to damage to vital organs over time. It is a common disease worldwide, affecting around 422 million individuals living in middle- and low-income countries, which make up most of the population. Unfortunately, diabetes results in 1.5 million deaths annually. Diabetic patients are at a higher risk for developing cardiovascular conditions. Diabetic heart disease constitutes multiple genres, including diabetic cardiomyopathy, coronary artery disease, and heart failure. Hypoglycaemic agents aim to prevent these metabolic issues however some of these are cardiotoxic in nature. In contrast, other hypoglycaemic agents work beyond controlling glycaemic levels with their cardioprotective properties. Given that there is an alarming increase in diabetic heart disease cases universally, we have attempted to review the existing data on the topic and the effects of hypoglycaemic drugs on heart diseases.

A Review on the Natural Products in Treatment of Diabetic Cardiomyopathy (DCM).

Diabetic cardiomyopathy is an insidious and fatal disease, imposing major financial and social burdens on affected individuals. Among the various methods proposed for the treatment of diabetic cardiomyopathy (DCM), treatments with natural products have achieved promising results due to their high efficiency and minimal side-effects. Literature was searched, analyzed, and collected using databases, including PubMed, Web of Science, Excerpt Medica, Science Direct, and Springer. In this study, we reviewed the DCM-related studies on 72 representative natural products. These natural products have been confirmed to be applicable in the therapeutic intervention of DCM, acting through various mechanisms such as the amelioration of metabolic abnormalities, protecting the mitochondrial structure and function, anti-oxidant stress, anti-inflammatory, anti-fibrosis, regulation of Ca 2 + homeostasis and regulation of programmed cell death. The nuclear factor kappa B (NF- κ B), nuclear factor erythroid 2-related factor 2 (Nrf-2), and transforming growth factor- ß (TGF- ß ) have been extensively studied as high frequency signaling pathways for natural product intervention in DCM. The effectiveness of natural products in treating DCM has been revealed and studied, which provides a reference for DCM-specific drug discovery.

Integrative Analyses of Circulating Proteins and Metabolites Reveal Sex Differences in the Associations with Cardiac Function among DCM Patients.

Dilated cardiomyopathy (DCM) is characterized by reduced left ventricular ejection fraction (LVEF) and left or biventricular dilatation. We evaluated sex-specific associations of circulating proteins and metabolites with structural and functional heart parameters in DCM. Plasma samples (297 men, 71 women) were analyzed for proteins using Olink assays (targeted analysis) or LC-MS/MS (untargeted analysis), and for metabolites using LC MS/MS (Biocrates AbsoluteIDQ p180 Kit). Associations of proteins (n = 571) or metabolites (n = 163) with LVEF, measured left ventricular end diastolic diameter (LVEDDmeasured), and the dilation percentage of LVEDD from the norm (LVEDDacc. to HENRY) were examined in combined and sex-specific regression models. To disclose protein-metabolite relations, correlation analyses were performed. Associations between proteins, metabolites and LVEF were restricted to men, while associations with LVEDD were absent in both sexes. Significant metabolites were validated in a second independent DCM cohort (93 men). Integrative analyses demonstrated close relations between altered proteins and metabolites involved in lipid metabolism, inflammation, and endothelial dysfunction with declining LVEF, with kynurenine as the most prominent finding. In DCM, the loss of cardiac function was reflected by circulating proteins and metabolites with sex-specific differences. Our integrative approach demonstrated that concurrently assessing specific proteins and metabolites might help us to gain insights into the alterations associated with DCM.