Search Results (85)

Background/Objectives: High-risk percutaneous coronary interventions (HR-PCIs) often require mechanical circulatory support (MCS) to maintain hemodynamic stability. Intra-aortic balloon pump (IABP) and percutaneous left ventricular assist device (PLVAD) are two commonly used MCS devices that differ in their mechanisms. We aimed to evaluate and compare the clinical outcomes associated with IABP and PLVAD use in HR-PCIs without cardiogenic shock. Methods: We conducted a search of PubMed, Scopus, Cochrane, Mendeley, Web of Science, and Embase to identify relevant randomized controlled trials and cohort studies, and we included 13 studies for the systematic review and meta-analysis. The primary goal was to define the difference in early mortality (in-hospital and 30-day mortality), major bleeding, and major adverse cardiovascular event (MACE) components (cardiogenic shock, acute kidney injury (AKI), and stroke/TIA) in IABP and PLVAD. We used a random-effects model with the Mantel–Haenszel statistical method to estimate odds ratios (ORs) and 95% confidence intervals. Results: Among 1 trial and 12 cohort studies (35,554 patients; 30,351 IABP and 5203 PLVAD), HR-PCI with IABP was associated with a higher risk of early mortality (OR = 1.53, 95% CI [1.21, 1.94]) and cardiogenic shock (OR = 2.56, 95% CI [1.98, 3.33]) when compared to PLVAD. No significant differences were found in the rates of arrhythmia, major bleeding, AKI, stroke/TIA, or hospital length of stay. Conclusions: In high-risk PCIs, PLVAD use is associated with lower early mortality and cardiogenic shock risk compared to IABP, with no significant differences in other major outcomes. Full article

Background: Human milk oligosaccharides (HMOs) serve as critical bioactive components supporting infant growth and development. However, the influence of maternal metabolic factors during lactation on HMOs remains to be fully elucidated. This study aimed to investigate the association between maternal metabolic factors and HMOs, as well as the potential mediating effects of these factors. Methods: An observational cross-sectional study was conducted in Central South China, enrolling 196 lactating mothers. HMOs were quantified using liquid chromatography-tandem mass spectrometry. Maternal metabolic factors were assessed through physical examinations. Associations between metabolic factors and HMOs were analyzed using linear regression, and mediation effects were evaluated. Results: HMOs from Central South China were predominantly composed of neutral fucosylated HMOs. Significant differences were observed in the levels of several HMOs across maternal age groups and lactation periods. The concentration of 3′-sialyllactose (3′-SL) exhibited a negative association with the pre-pregnancy body mass index (BMI) (β = −0.16, 95% CI: −0.29, −0.03; p = 0.02), while a positive association was found with maternal heart rate (β = 0.14, 95% CI: 0.01, 0.27; p = 0.04). However, these associations were different between secretor and non-secretor mothers. Associations of 3′-SL with pre-pregnancy BMI and maternal HR were only found in the secretor mothers. Triglycerides and low-density lipoprotein cholesterol mediated the associations between maternal pre-pregnancy BMI and 3′-sialyllactose (3′-SL). Conclusions: The variations of several HMOs among mothers from Central South China were associated with maternal age and lactation period. The concentration of 3′-SL was negatively correlated with maternal pre-pregnancy BMI. The potential mechanism underlying the influence of maternal BMI on 3′-SL levels may involve maternal lipid metabolism and genetic factors. Full article

G-quadruplex (G4) structures have emerged as critical regulatory elements in viral genomes and represent potential targets for antiviral intervention. In this study, we identified and characterized G4 structures in the unique long (UL) region of the Pseudorabies virus (PRV) genome, highlighting their role as novel antiviral targets. Bioinformatic analysis revealed two guanine-rich regions (R1 and R2) that form stable G4 structures, as confirmed by fluorescence assays, circular dichroism (CD) spectroscopy, and immunofluorescence staining. Notably, these G4 structures exhibit a tandem repeat arrangement, a previously unreported feature in the PRV genome. Epiberberine (EPI), a natural G4-stabilizing ligand, bound to and stabilized these structures, leading to the inhibition of Taq polymerase progression. Functional assays demonstrated that EPI effectively suppressed PRV replication in vitro while having no significant impact on viral entry or release. In vivo, EPI treatment significantly improved survival rates and reduced viral loads in multiple organs, including the brain, heart, lungs, and kidneys of infected mice. These findings provide new insights into the role of G4 structures in PRV replication and demonstrate that EPI exhibits potential antiviral activity by targeting G4 structures. Full article

Background: Plasmalogens (Pls) are phospholipids with a unique structure, abundant in the brain and heart. Due to their chemical instability and analytical difficulties, less information is available compared to other phospholipids. The importance of Pls in several cellular processes is known, one of which is their protective effect against oxidative damage. The physiological role of Pls in human development has not been elucidated. Despite their clinical importance, the quantitative analysis of Pls in children’s plasma has been limited. Methods: This study aims to determine the plasma levels of Pls in prepubertal children using liquid chromatography/tandem mass spectrometry (LC-MS/MS). The plasma samples used were obtained from 9- to 12-year-old girls (n = 156) and boys (n = 178), n = 334 in total, who participated in the Hokkaido study. Results: Ethanolamine plasmalogen (PlsEtn) and choline plasmalogen (PlsCho), both carrying eicosapentaenoic acid, were significantly lower in girls than in boys. In both sexes, the plasmalogen levels for the 12-year-old children were lower than those for the 9-year-old children. PlsCho (16:0/18:2) was lower in the overweight children than in the normal-weight children for both sexes. PlsEtn (18:0/20:4) was the most abundant ethanolamine-type plasmalogen in both sexes. Conclusions: This study is the first report on plasmalogen levels and molecular types in children’s plasma. This study provides the information needed to understand the role of Pls in human developmental processes and may open up new opportunities in the future to control age-related changes in Pls. Full article

Heart failure (HF) remains a major cause of mortality worldwide. While novel approaches, including gene and cell therapies, show promise, efficient delivery methods for such biologics to the heart are critically needed. One emerging strategy is lung-to-heart delivery using nanoparticle (NP)-encapsulated biologics. This study examines the efficiency of delivering a therapeutic peptide conjugated to a cell-penetrating peptide (CPP) to the heart via the lung-to-heart route through intratracheal (IT) injection in mice. The CPP, a tandem repeat of NP2 (dNP2) derived from the human novel LZAP-binding protein (NLBP), facilitates intracellular delivery of the therapeutic payload. The therapeutic peptide, SE, is a decoy peptide designed to inhibit protein phosphatase 1 (PP1)-mediated dephosphorylation of phospholamban (PLN). Our results demonstrated that IT injection of dNP2-SE facilitated efficient delivery to the heart, with peak accumulation at 3 h post-injection. The administration of dNP2-SE significantly ameliorated morphological and functional deterioration of the heart under myocardial infarction. At the molecular level, dNP2-SE effectively prevented PLN dephosphorylation in the heart. Immunoprecipitation experiments further revealed that dNP2-SE binds strongly to PP1 and disrupts its interaction with PLN. Collectively, our findings suggest that lung-to-heart delivery of a CPP-conjugated therapeutic peptide, dNP2-SE, represents a promising approach for the treatment of HF. Full article

Chenopodium album L., as a folkloric herb, is traditionally used to treat poisonous insect bites, vitiligo, and other ailments. However, its impact on thrombosis remains unknown. In this study, we discovered that the ethanol extract of C. album exhibited a remarkable antithrombotic effect using a zebrafish thrombosis model for the first time. Activity evaluation showed that fraction CA-C could improve thrombus aggregation in the caudal vein, increase blood return in the heart, and alleviate the slowing of blood flow compared with those in the model group. Then, analysis by ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass (UPLC-Q-TOF-MS) identified 58 constituents of CA-C, with most of them belonging to flavonoids, alkaloids, and steroidal saponin components. Moreover, using a comprehensive strategy of network pharmacological analysis, transcriptomic assay, and RT-qPCR validation, we found that CA-C could mediate the TLR’s signaling pathway and its downstream MAPKs and PI3K/AKT signaling pathways to exert an antithrombotic effect. This study broadens the clinical application of plant C. album and provides new insight into the chemical profile, pharmacodynamics, and potential mechanisms of CA-C as candidate agents for treating thrombosis. Full article

Background and Objectives: Regular exercise is known to induce cardiovascular adaptations collectively referred to as “athlete’s heart”. While previous research has explored the morphological and functional cardiac adaptations in athletes, the relationship between vitamin D (25-hydroxyvitamin D [25(OH)D]) levels and echocardiographic parameters remains underexplored. This study aims to assess the association between 25(OH)D levels and structural and functional cardiac parameters using electrocardiographic (ECG) and echocardiographic evaluations in athletes. Materials and Methods: This case–control study included 93 male athletes, categorized into professional (n = 68) and recreational (n = 25) groups. Professional athletes were further divided into football (n = 19), weightlifting (n = 22), and running (n = 27) subgroups. Serum 25(OH)D levels were measured using high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS). Standard 12-lead ECG and transthoracic echocardiography were performed to assess cardiac structure and function. Data were analyzed using statistical tests that were appropriate for normal and non-normal distributions, with a significance level set at p < 0.05. Results: Athletes exhibited higher left ventricular interventricular septum (IVS) thickness and left ventricular posterior wall thickness (LVPWd) compared to the control group. Significant differences in diastolic function parameters, including early (E) and late (A) diastolic filling velocities and the E/A ratio, were observed among athlete subgroups. The weightlifting group showed lower end-systolic diameter (ESD) values than the football group. However, no statistically significant relationship was found between 25(OH)D levels and echocardiographic diastolic parameters. While more than half of the athletes had insufficient 25(OH)D levels (<30 ng/mL), their average values were higher than those reported in previous studies. Conclusions: This study demonstrates that 25(OH)D levels do not significantly influence echocardiographic diastolic parameters in athletes. However, notable differences in structural and functional cardiac findings were observed among different sports disciplines. These findings contribute to the understanding of cardiac adaptations in athletes and suggest that 25(OH)D may not play a crucial role in diastolic function. Further research is needed to explore the long-term effects of vitamin D on athletic cardiac performance. Full article

Enavogliflozin, a sodium–glucose cotransporter 2 inhibitor, was approved in 2022 by the Korean Ministry of Food and Drug Safety as a therapeutic agent for type 2 diabetes mellitus and has been investigated for expanded therapeutic efficacy in diabetic retinopathy and cardioprotection. In this study, we developed and validated an analytical method to precisely detect enavogliflozin in mouse plasma, employing liquid–liquid extraction combined with liquid chromatography–tandem mass spectrometry. Overall, the analytical method, covering a range of 5–3000 ng/mL, is reliable for investigating the time-concentration profiles of enavogliflozin, demonstrating acceptable accuracy, precision, extraction recovery, and minimal matrix effects without stability concerns as evidenced by assessments of post-treatment stability, freeze–thaw stability, and short-term stability of enavogliflozin. Pharmacokinetic profiles and all pharmacokinetic parameters of enavogliflozin in mice did not differ between fed and fasted states after oral administration of enavogliflozin (1 mg/kg). Additionally, no differences in the pharmacokinetic profiles of enavogliflozin were observed among single, 7-day repeated, and 14-day repeated oral administrations at 1 mg/kg. In the tissue distribution study, enavogliflozin showed the highest distribution in the kidneys, followed by the large intestine, stomach, small intestine, liver, heart, lungs, spleen, and testes after oral administration at both 1 and 3 mg/kg doses. Dose proportionality in tissue distribution was observed except for the kidneys. In conclusion, enavogliflozin can be administered without concern for pharmacokinetic changes, regardless of single or multiple dosing and whether in fed or fasted states. Furthermore, the tissue distribution profile may offer valuable insights into the therapeutic potential of this drug. Full article

Inflammation has been widely recognized as one of the major pathophysiological drivers of the development of atrial fibrillation (AF), which works in tandem with other risk factors of AF including obesity, diabetes, hypertension, and heart failure (HF). Our current understanding of the role of inflammation in the natural history of AF remains elusive; however, several key players, including the NLRP3 (NLR family pyrin domain containing 3) inflammasome, have been acknowledged to be heavily influential on chronic inflammation in the atrial myocardium, which leads to fibrosis and eventual degradation of its electrical function. Nevertheless, our current methods of pharmacological modalities with reported immunomodulatory properties, including well-established classes of drugs e.g., drugs targeting the renin–angiotensin–aldosterone system (RAAS), statins, and vitamin D, have proven effective in reducing the overall risk of developing AF, the onset of postoperative atrial fibrillation (POAF), and reducing overall mortality among patients with AF. This might bring hope for further progress in developing new treatment modalities targeting cellular checkpoints of the NLRP3 inflammasome pathway, or revisiting other well-known anti-inflammatory drugs e.g., colchicine, vitamin C, nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticosteroids, and antimalarial drugs. In our review, we aim to find relevant upstream anti-inflammatory treatment methods for the management of AF and present the most current real-world evidence of their clinical utility. Full article

Mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies have been a part of the Slovenian newborn screening (NBS) program since 2018. We describe a case of early lethal presentation of MTPD/LCHADD in a term newborn. The girl was born after an uneventful pregnancy and delivery, and she was discharged home at the age of 3 days, appearing well. At the age of 4 days, she was found without signs of life. Resuscitation was not successful. The NBS test performed using tandem mass spectrometry (MS/MS) showed a positive screen for MTPD/LCHADD. Genetic analysis performed on a dried blood spot (DBS) sample identified two heterozygous variants in the HADHA gene: a nucleotide duplication introducing a premature termination codon (p.Arg205Ter) and a nucleotide substitution (p.Glu510Gln). Post-mortem studies showed massive macro-vesicular fat accumulation in the liver and, to a smaller extent, in the heart, consistent with MTPD/LCHADD. A neonatal acute cardiac presentation resulting in demise was suspected. We conducted a systematic literature review of early neonatal deaths within 14 days postpartum attributed to confirmed fatty acid oxidation disorders (FAODs), which are estimated to account for 5% of sudden infant deaths. We discuss the pitfalls of the NBS for MTPD/LCHADD. Full article

Background/Objectives: Septic cardiomyopathy (SCM) is a severe cardiac complication of sepsis, characterized by cardiac dysfunction with limited effective treatments. This study aimed to identify repurposable drugs for SCM by integrated multi-omics and network analyses. Methods: We generated a mouse model of SCM induced by lipopolysaccharide (LPS) and then obtained comprehensive metabolic and genetic data from SCM mouse hearts using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) and RNA sequencing (RNA-seq). Using network proximity analysis, we screened for FDA-approved drugs that interact with SCM-associated pathways. Additionally, we tested the cardioprotective effects of two drug candidates in the SCM mouse model and explored their mechanism-of-action in H9c2 cells. Results: Network analysis identified 129 drugs associated with SCM, which were refined to 14 drug candidates based on strong network predictions, proven anti-infective effects, suitability for ICU use, and minimal side effects. Among them, acetaminophen and pyridoxal phosphate significantly improved cardiac function in SCM moues, as demonstrated by the increased ejection fraction (EF) and fractional shortening (FS), and the reduced levels of cardiac injury biomarkers: B-type natriuretic peptide (BNP) and cardiac troponin I (cTn-I). In vitro assays revealed that acetaminophen inhibited prostaglandin synthesis, reducing inflammation, while pyridoxal phosphate restored amino acid balance, supporting cellular function. These findings suggest that both drugs possess protective effects against SCM. Conclusions: This study provides a robust platform for drug repurposing in SCM, identifying acetaminophen and pyridoxal phosphate as promising candidates for clinical translation, with the potential to improve treatment outcomes in septic patients with cardiac complications. Full article

Background: An increasing number of heart failure with preserved ejection fraction (HFpEF) syndromes has been reported in tandem with increasing age and burdens of obesity and cardiometabolic disorders. Identifying possible risk and modulatory HFpEF factors has significant epidemiological and clinical value. This study aimed to assess the prevalence of echocardiographic diagnostic criteria of left ventricular dysfunction in patients with chronic coronary syndrome depending on rosuvastatin therapy. Method: There were 81 (33 (41%) male) consecutive patients with a median age of 70 (62–75) years, presenting with stable heart failure symptoms according to the New York Heart Association (NYHA) classification I to III. They presented with chronic coronary syndrome and were hospitalized between March and August 2024. Patients were divided according to the type of long-term lipid-lowering therapy into patients with rosuvastatin and with other statin therapy. The echocardiographic analysis based on diastolic dysfunction evaluation was performed on admission and compared with demographical, clinical, and laboratory results. Results: In the multivariable model for diastolic dysfunction prediction in the analyzed group based on three echocardiographic parameters, septal E’ below 7 cm/s, lateral E’ below 10 cm/s, and LAVI above 34 mL/m², the following factors were found to be significant: sex (male) (OR: 0.19, 95% CI: 0.04–0.83, p = 0.027), obesity (defined as BMI > 30) (OR: 12.78, 95% CI: 2.19–74.50, p = 0.005), and rosuvastatin therapy (OR: 0.09, 95% CI: 0.02–0.51, p = 0.007). Conclusions: Rosuvastatin therapy can be regarded as a possible protective therapy against left ventricular diastolic dysfunction in chronic coronary syndrome. Full article

Background: Exercise or vitamin D intervention can reduce the risk of arterial stiffness; however, the underlying mechanisms of lipid metabolism remain unexplored. To examine the effects of a 12-week moderate and vigorous exercise program (65–80% maximal heart rate, 60 min/time, 2~3 times/week) with or without vitamin D supplementation (1000 IU/day) on the reduction in arterial stiffness and further explore whether the effects of interventions could be associated with the basal lipidome among patients with Type 2 diabetes mellitum (T2DM). Method: 61 patients with T2DM were randomly assigned to the following groups: control (CON, n = 15), exercise (EX, n = 14), vitamin D (VD, n = 16), and exercise + vitamin D (EX + VD, n = 16). Arterial stiffness risk factors (ankle–brachial index (ABI); brachial–ankle pulse wave velocity (baPWV), systolic blood pressure (SBP), and diastolic blood pressure (DBP)) were evaluated before and after the intervention. The plasma lipidome was determined using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Machine learning was applied to establish prediction models for the responsiveness to arterial stiffness. Result: Vitamin D supplementation could inhibit the decrease in the ankle–brachial index (mean ± SD: EX + VD and VD, −0.001 ± 0.058; EX + CON, −0.047 ± −0.089; p = 0.03). We observed high inter-individual variability in the arterial stiffness risk factors in response to the interventions. We also found that optimally selecting the lipid predictors at baseline, such as SM d44:6, LPE 18:2, and Hex2Cer 29:0, could enhance the predictive power by 100% for arm SBP changes in the exercise group. Basal levels of Cer (33:1) and GM3 (44:4) could enhance the predictive power by 100% for changes in baPWV in the vitamin D group. Conclusions: A 12-week vitamin D supplementation was beneficial in preventing arterial stiffness. Compared with traditional clinical risk factors, specific lipids at baseline could significantly improve the ability to predict intervention-induced changes in the reduction of arterial stiffness. Full article

Resveratrol (trans-3,5,4′-trihydroxystilbene, RES) is one of the most well-known natural products with numerous health benefits. To explore the nutraceutical potentials of some dietary RES derivatives including isorhapontigenin (trans-3,5,4′-trihydroxy-3′-methoxystilbene, ISO), oxyresveratrol (trans-3,5,2′,4′-tetrahydroxystilbene, OXY) and pterostilbene (trans-3,5-dimethoxy-4′-hydroxystilbene, PTS), their impacts on metabolism and health were assessed in Sprague Dawley rats after a two-week daily oral administration at the dose of 100 µmol/kg/day. Non-targeted metabolomic analyses were carried out with the liver, heart, brain and plasma samples using gas chromatography–tandem mass spectrometry (GC-MS/MS). Notable in vivo health benefits were observed, as the rats received ISO, PTS or RES showed less body weight gain; the rats received OXY or RES displayed healthier fasting blood glucose levels; while all of the tested stilbenes exhibited cholesterol-lowering effects. Additionally, many important metabolic pathways such as glycolysis, pentose phosphate pathway, tricarboxylic acid cycle and fatty acid oxidation were found to be modulated by the tested stilbenes. Besides the reaffirmation of the well-known beneficial effects of RES in diabetes, obesity, cardiovascular disease and Alzheimer’s disease, the metabolomic analyses also suggest the anti-diabetic, cardio-, hepato- and neuro-protective activities of ISO; the anti-diabetic, cardio-, hepato- and neuro-protective effects of OXY; and the anti-aging, anti-inflammatory, cardio-, hepato- and neuro-protective potential of PTS. Interestingly, although these stilbenes share a similar structure, their biological activities appear to be distinct. In conclusion, similarly to RES, ISO, OXY and PTS have emerged as promising candidates for further nutraceutical development. Full article

Chronic heart failure (CHF) is a complex clinical syndrome, associated with frailty, higher fall rates, and frequent hospitalizations. Heart Failure (HF) and preserved ejection fraction (HFpEF) is defined as a condition where a patient with HF have a diagnosis of left ventricular ejection fraction (LVEF) of ≥ 50%. The risk of HFpEF increases with age and is related to higher non-cardiovascular mortality. The aim of this study was to evaluate static balance and examine the effect of task difficulty on the discriminating power of balance control between patients with HFpEF (Patients with HFpEF) and their healthy controls. Moreover, the associations between static balance parameters, balance confidence, falls, lean muscle mass, and strength were assessed. Seventy two patients with HFpEF (mean age: 66.0 ± 11.6 years) and seventy two age- and gender-matched healthy individuals (mean age: 65.3 ± 9.5 years) participated in this study. Participants underwent a 30 s bilateral stance (BS) test and a 20 s Tandem-Romberg stance (TRS) on a force platform, evaluating the Range and Standard Deviation of Center of Pressure (COP) displacement parameters in both axes. Balance confidence was evaluated by the Activities-Specific Balance Confidence (ABC) Scale, and the number of falls during the last year was recorded. Lower limb strength was measured using an isokinetic dynamometer, isometric leg strength, and a Sit-to-Stand test. Bioelectrical impedance analysis was conducted to assess lean fat mass, lean fat mass index, and lean%. Patients with HFpEF presented with lower static balance in BS and TRS compared to healthy controls (p < 0.05), lower balance confidence by 21.5% (p < 0.05), and a higher incidence of falls by 72.9% (p < 0.05). BS was a better descriptor of the between-group difference. Furthermore, static balance, assessed in controlled lab conditions, was found to have little if no relationship to falls, strength, lean muscle mass, and balance confidence. Although no correlation was noted between the static balance parameters and falls, the fall rate was related to balance confidence, age, muscle strength, and lean fat. Full article