Heart Damage Research Articles

Early-life exposure to lead changes cardiac development and compromises long-term cardiac function

Lead (Pb) is widely used in industrial and daily-use consumer products. Early-life exposure may increase the risk of lead-related heart problems in childhood. However, the effects of early-life lead exposure on fetal heart development and long-term cardiac outcomes are unknown. In this study, pregnant ICR mice were exposed to lead acetate trihydrate (50 mg/kg/d) via oral gavage from gestation day 1.5 until offspring weaning. Thereafter, the second hit model was established, two groups of offspring (4 weeks old) were either administered sterile saline or Angiotensin II (Ang II) for 4 weeks until euthanasia. We investigated lead-induced offspring heart damage from embryonic period to adulthood by echocardiographic analysis, pathological H&E staining, and ultrastructural examination, as well as mitochondrial function detection. The results showed early-life lead exposure predisposed offspring mice to decreased ejection fraction, increased left ventricular volume, accompanied by hypertrophy and dilation, cardiomyocyte sarcomere dysplasia, abnormal mitochondrial structure, mitochondrial dysfunction, and decreased expression of key sarcomeric and mitochondrial genes, rendering them more susceptible to cardiac hypertrophy, vascular wall thickening, cardiac fibrosis, apoptosis, and heart failure induced by Ang II infusion. This study elucidates early-life low dose lead exposure compromises cardiac development and exacerbates second hit-induced cardiac pathological responses in adulthood, which furnishes crucial scientific evidence pertaining to the cardiac toxicity and risk evaluation associated with early-life exposure to lead.

Euterpe oleracea extract (açaí) exhibits cardioprotective effects after chemotherapy treatment in a breast cancer model.

Açaí, a Brazilian native fruit, has already been demonstrated to play a role in the progress of breast cancer and cardiotoxicity promoted by chemotherapy agents. Thus, the present study aimed to evaluate the combined use of açaí and the FAC-D chemotherapy protocol in a breast cancer model in vivo. Mammary carcinogenesis was induced in thirty female Wistar rats by subcutaneous injection of 25mg/kg 7,12-dimethylbenzanthracene (DMBA) in the mammary gland. After sixty days, the rats were randomized into two groups: treated with 200mg/kg of either açaí extract or vehicle, via gastric tube for 45 consecutive days. The FAC-D protocol was initiated after 90 days of induction by intraperitoneal injection for 3 cycles with a 7-day break each. After treatment, blood was collected for haematological and biochemical analyses, and tumours were collected for macroscopic and histological analyses. In the same way, heart, liver, and kidney samples were also collected for macroscopic and histological analyses. Breast cancer was found as a cystic mass with a fibrotic pattern in the mammary gland. The histological analysis showed an invasive carcinoma area in both groups; however, in the saline group, there was a higher presence of inflammatory clusters. No difference was observed regarding body weight, glycaemia, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and urea in either group. However, açaí treatment decreased creatine kinase (CK), creatine kinase MB (CKMB), troponin I and C-reactive protein levels and increased the number of neutrophils and monocytes. Heart histopathology showed normal myocardium in the açaí treatment, while the saline group presented higher toxicity effects with loss of architecture of cardiac tissue. Furthermore, the açaí treatment presented greater collagen distribution, increased hydroxyproline concentration and lower H2AX immunostaining in the heart samples. Açaí decreased the number of inflammatory cells in the tumor environment and exhibited protection against chemotherapy drug cardiotoxicity with an increased immune response in animals. Thus, açaí can be considered a promising low-cost therapeutic treatment that can be used in association with chemotherapy agents to avoid heart damage.

Exploring Cardiac Effects After Oxytocin 2.5 I U or Carbetocin 100 μg: A Randomised Controlled Trial in Women Undergoing Planned Caesarean Delivery

(Eur J Anaesthesiol. 2022;39:928–938) While oxytocin can be cardioprotective at physiologic levels, higher concentrations are used to prevent postpartum hemorrhage (PPH) and can induce hypotension, ST-depression, tachycardia, arrhythmias, and prolongation of the QTc interval. Further cardiovascular (CV) effects caused directly by oxytocin can result in fatalities in patients with underlying myocardial disease. Such acute risk for susceptible patients warrants characterization of CV changes induced by intravenous oxytocin and its commonly used analog carbetocin as administered to prevent PPH. While carbetocin has demonstrated comparable or improved effect for stimulating uterine contractions and has similar hemodynamic effects to oxytocin, the comparative prevalence of adverse cardiac events is unknown. Myocardial distress can be measured by the release of circulating troponin I (cTnI) and troponin T (cTnT), which are considered indirect indicators of ischemic heart damage. This exploratory Phase 4 randomized trial queried the difference in troponin release following oxytocin or carbetocin administration to approximate the incidence of cardiac adverse events when used to prevent PPH in women undergoing planned cesarean delivery (CD).

Oncostatin M/Oncostatin M Receptor Signal Induces Radiation-Induced Heart Fibrosis by Regulating SMAD4 in Fibroblast

Radiation-induced heart fibrosis (RIHF) is a severe consequence of radiation-induced heart damage (RIHD) leading to impaired cardiac function. The involvement of oncostatin M (OSM) and its receptor (OSMR) in RIHD remains unclear. This study aimed to investigate the specific mechanism of OSM/OSMR in RIHF/RIHD. RNA sequencing was performed on heart tissues from a RIHD mouse model. OSM levels were assessed in serum samples obtained from patients receiving thoracic radiation therapy (RT), as well as in RIHF mouse heart tissues and serum using enzyme-linked immunosorbent assay. Fiber activation was evaluated through costimulation of primary cardiac fibroblasts and NIH3T3 cells with RT and OSM, using Western blotting, immunofluorescence, and quantitative Polymerase Chain Reaction (qPCR). Adeno-associated virus serotype 9-mediated overexpression or silencing of OSM specifically in the heart was performed in vivo to assess cardiac fibrosis levels by transthoracic echocardiography and pathologic examination. The regulatory mechanism of OSM on the transcription level of SMAD4 was further explored in vitro using mass spectrometric analysis, chromatin immunoprecipitation-qPCR, and DNA pull-down. OSM levels were elevated in the serum of patients after thoracic RT as well as in RIHF mouse cardiac endothelial cells and mouse serum. The OSM rate (post-RT/pre-RT) and the heart exposure dose in RT patients showed a positive correlation. Silencing OSMR in RIHF mice reduced fibrosis, while OSMR overexpression increased fibrotic responses. Furthermore, increased OSM promoted histone acetylation (H3K27ac) in the SMAD4 promoter region, influencing SMAD4 transcription and subsequently enhancing fibrotic response. The findings demonstrated that OSM/OSMR signaling promotes SMAD4 transcription in cardiac fibroblasts through H3K27 hyperacetylation, thereby promoting radiation-induced cardiac fibrosis and manifestations of RIHD.

Assessment of Extent of Myocardial Injury in Patients Undergoing Transvenous Implantation of Pacemaker Using Cardiac Troponin I (cTnI) as a Marker of Structural Heart Damage and It’s Relation to Different Sites of RV Implantation

Abstract Aim and objectives The aim of the study is to assess the extent of myocardial injury in patients undergoing trans-venous implantation of pacemaker using cardiac troponin I (cTnI) as a marker of myocardial injury and it’s relation to different sites of RV pacing and number of screwing. Patients and Methods This study included 50 patients undergoing Trans-venous Implantation of single or dual chamber permanent pacemakers at Ain Shams University Hospitals during the period from February 2020 to August 2020, divided into 2 equal groups according to the site of RV lead implantation, 25 patients RV lead implanted in the Apex and 25 patients RV lead implanted in the Septum. Results All patients had rise in Troponin I after implantation of pacemaker indicating that there is significant relationship between trans-venous implantation of permanent pacemaker and incidence of myocardial injury. Comparing the RV septal pacing group to the RV apical pacing group, results showed that septal RV pacing caused more rise in cardiac troponin I after implantation than in apical pacing group indicating that there is a significant relationship between site of RV pacing and extent of myocardial injury being more in septal RV pacing than apical RV pacing. Furthermore, our study showed that regarding active fixation of RV lead into the myocardium, increasing number of trials of screwing the lead in different sites to achieve the best pacing threshold causes more rise in cardiac troponin I. So, there is a significant relationship between number of screwing and extent of myocardial injury. Conclusion We conclude that trans-venous implantation of permanent pacemakers is associated with an increased incidence of myocardial injury and septal RV pacing is associated with more extent of myocardial injury than apical RV pacing. Also, increasing number of trials of active fixation by screwing the RV leads into the myocardium is associated with more extent of myocardial injury.

Evaluation of Oxidative Status, Cytokines, Acute Phase Proteins and Cardiac Damage Markers in Sheep Naturally Infected with Babesia ovis.

Babesiosis is a tick-borne disease caused by protozoon species in the Babesia genus of the Babesiadae family. The systemic inflammatory response induced by infection is considered to be an important feature of the pathophysiology of ovine babesiosis. In this study, it was aimed to determine serum oxidative status, levels of some cytokines, acute phase proteins and heart damage markers in babesiosis infection. A sample of 40 sheep was used for this purpose, of which 20 were healthy and 20 were infected with Babesia ovis. Babesia infection was diagnosed from Giemsa-stained peripheral blood smears. Infection was also confirmed by the polymerase chain reaction (PCR). Sera from blood samples was tested for oxidative stress parameters (malondialdehyde [MDA], total antioxidant status [TAS], superoxide dismutase [SOD], catalase [CAT] and glutathione peroxidase [GPx]), cytokines (interleukins IL-6, IL-1β, IL-10, tumour necrosis factor α (TNF-α) and interferon-ϒ [IFN-ϒ]), acute-phase proteins (C-reactive protein [CRP], serum amyloid A [SAA] and haptoglobin [Hp]) and specific (troponin I [cTnI], creatine kinase-MB [CK-MB]) and nonspecific (lactate dehydrogenase [LDH], aspartate transaminase [AST]) cardiac damage markers. MDA, SOD, CAT, Hp, TAS, IL-6, IL-10, TNF-α, IL-1β, INF-γ, AST, LDH, CK-MB mass and troponin I values were higher in the patient group than in the healthy group (P < 0.05). However, there was not found to be a statistical difference between the healthy and patient groups in terms of GPx, SAA and CRP values (P > 0.05). It can be stated that serum levels of oxidative stress, some acute phase proteins and cardiac damage markers may increase in naturally infected sheep with babesiosis.

E45 Kawasaki syndrome-related heart disease before and during the COVID-19 pandemic

Abstract Introduction Kawasaki disease (kDa) is an acute febrile systemic panvascularitis that affects medium-caliber arteries with a strong predilection for the coronary arteries. It is the leading cause of acquired heart disease in children under 5 years of age. However, after the COVID-19 pandemic, we see a change in the profile of cardiac involvement. Objective To describe the clinical, paraclinical, and evolutionary characteristics of cardiac damage in children managed for Kawasaki or Kawasaki-Like syndrome before and during the Covid19 pandemic. Materials and Methods This is a retrospective, descriptive study conducted over a period of five years (1st January 2017 to 31st December 2021). Result We collected 30 cases of patients hospitalized with Kawasaki disease, between January 2017 and December 2021: 11 cases with Kawasaki syndrome before COVID-19; and 19 cases with Kawasaki syndrome after COVID-19. The mean age and standard deviation (SD) at diagnosis was 42 (±37.8) months before the pandemic vs 81 (±34.7) months after the pandemic. The sex ratio was 0.5 (4 girls and 7 boys) before the pandemic vs 0.7 (8 girls and 11 boys) after the pandemic. Heart damage was found in 2 cases before the pandemic (coronary aneurysm type) vs 3 cases after the pandemic, mainly cardiogenic shock. The mean time from the first transthoracic ultrasound to fever was 11.3 days before the pandemic, vs 5.8 days after the pandemic. Transthoracic ultrasound showed 2 cases of coronary aneurysm before the pandemic, with a Z score exceeding 2.5SD; vs 7 cases of heart failure after the pandemic with a decrease in left ventricular ejection fraction. The ASAI score (a score that assesses the risk of coronary artery disease) was &amp;gt;6 in 1 case before the pandemic vs in 0 cases after the pandemic. The average predictive score for cardiac involvement was 4.2 (±1.4) before the pandemic, vs 3.5 (±1.5) after the pandemic. The outcome was favorable in all cases despite a more severe picture after the COVID-19 pandemic. Conclusion The change in the pattern of cardiac involvement in Kawasaki disease following the emergence of COVID-19 must be taken into account in order to manage an influx of patients with severe Kawasaki disease.

NAC Pre-Administration Prevents Cardiac Mitochondrial Bioenergetics, Dynamics, Biogenesis, and Redox Alteration in Folic Acid-AKI-Induced Cardio-Renal Syndrome Type 3.

The incidence of kidney disease is increasing worldwide. Acute kidney injury (AKI) can strongly favor cardio-renal syndrome (CRS) type 3 development. However, the mechanism involved in CRS development is not entirely understood. In this sense, mitochondrial impairment in both organs has become a central axis in CRS physiopathology. This study aimed to elucidate the molecular mechanisms associated with cardiac mitochondrial impairment and its role in CRS development in the folic acid-induced AKI (FA-AKI) model. Our results showed that 48 h after FA-AKI, the administration of N-acetyl-cysteine (NAC), a mitochondrial glutathione regulator, prevented the early increase in inflammatory and cell death markers and oxidative stress in the heart. This was associated with the ability of NAC to protect heart mitochondrial bioenergetics, principally oxidative phosphorylation (OXPHOS) and membrane potential, through complex I activity and the preservation of glutathione balance, thus preventing mitochondrial dynamics shifting to fission and the decreases in mitochondrial biogenesis and mass. Our data show, for the first time, that mitochondrial bioenergetics impairment plays a critical role in the mechanism that leads to heart damage. Furthermore, NAC heart mitochondrial preservation during an AKI event can be a valuable strategy to prevent CRS type 3 development.

The role of alcohol extract of cranberry in improving serum indices of experimental metaproterenol-induced heart damage in rats.

Cranberry offers numerous cardiovascular benefits. According to several studies, this fruit promotes the oxidation of low-density lipoprotein, enhances high-density lipoprotein, reduces platelet coagulation, and improves vascular activity. Albino male rats were divided into five groups (n = 5 per group). The control group received intraperitoneal administration of normal saline. The second group was injected with metaproterenol (MET) 3 days a week for 4 weeks. The third, fourth, and fifth groups were given cranberry extract in doses of 75, 100, and 150, respectively, along with heart-damaging drugs. Blood samples were collected and sent to the laboratory on the fourth weekend and 1 week after completing the injections in the fourth week (the sixth weekend) for analyzing serum factors such as cardiac creatine kinase MB, cardiac troponin I (cTnI), and aspartate aminotransferase (AST). The serum activity of the cardiac evaluation parameters in the fourth week demonstrated a highly significant correlation among the groups with respect to AST and cTnI (p < .001). Additionally, a significant relationship was observed between AST and cTnI within the target groups (p < .05). Ultimately, the findings indicated that the consumption of cranberry extract, due to its impact on heart function, could effectively modify serum indicators associated with heart damage. The utilized extract also exhibited efficacy, albeit with variable effects. Therefore, it is recommended to use cranberry extract synergistically with other chemical and herbal medications to achieve more sustained effects.

Early and Accurate Detection of Radiation-induced Heart Damage by Cardiodynamicsgram.

Cardiodynamicsgram (CDG) has emerged recently as a noninvasive spatiotemporal electrocardiographic method for subtle cardiac dynamics information analysis within electrocardiogram (ECG). This study explored the feasibility of CDG for detecting radiation-induced heart damage (RIHD) in a rat model. A single radiation dose of 40Gy was delivered to the cardiac apex of female Wistar rats. First, CDG was generated through dynamic modeling of ECG signals using the deterministic learning algorithm. Furthermore, CDG indexes were calculated using the wavelet transform and entropy. In this model, CDG entropy indexes decreased significantly after radiotherapy. The shape of CDG changed significantly after radiotherapy (irregular shape) compared with controls (regular shape). Macrophage and fibrosis in myocardium of rats increased significantly after radiotherapy. CDG changes after radiotherapy were significantly correlated with histopathological changes and occurred significantly earlier than histopathological changes. This study provides an experimental basis for the clinical application of CDG for the early detection of RIHD.

Cardioprotective effects of Schisantherin A against isoproterenol-induced acute myocardial infarction through amelioration of oxidative stress and inflammation via modulation of PI3K-AKT/Nrf2/ARE and TLR4/MAPK/NF-κB pathways in rats

Background and aimsThe scientific community is concerned about cardiovascular disease mortality and morbidity, especially myocardial infarction (MI). Schisantherin A (SCA), a dibenzocyclooctadiene lignan monomer found in S. chinensis fruits has cardiovascular advantages such as increasing NO production in isolated rat thoracic aorta and reducing heart damage caused by ischemia-reperfusion (I/R) through decreasing apoptosis. The present study was undertaken to explore the potential effects of SCA on ISO-induced myocardial infarction in rats.MethodsRats were randomly allocated to four groups: control; ISO-treated, and two additional groups of ISO + SCA (5 or 10 mg/kg body weight). All SCA-treated groups were administered with SCA for 20 days and all ISO groups were challenged with ISO on days 19 and 20.ResultsSCA significantly attenuated ISO-induced rise in heart/body weight ratio, myocardial infarct size, and cardiac functional biomarkers (CK-MB, cTnI and BNP). SCA pre- and co-treatment resulted in a significant reduction in oxidative stress (via MDA, NO and GSH and increased activities of SOD, CAT and GPx) and inflammation (via decreased levels of TNF-α, IL-6 and IL-1β) markers when compared to the same levels in cardiac tissue of ISO-treated rats. This study also showed that SCA protects ISO-induced oxidative stress and inflammation by activating the PI3K-AKT/Nrf2/ARE pathway and suppressing TLR4/MAPK/NF-κB pathways. Furthermore, SCA treatment protected histopathological alterations observed in only ISO-treated cardiac transverse sections of rats.ConclusionIn conclusion, the findings of this study suggest that SCA protects against cardiac injury in the ISO-induced MI model of rats.

Serpina3c attenuates adipose tissue and heart damage during obesity by inhibiting oxidative stress and endoplasmic reticulum stress

Serpina3c attenuates adipose tissue and heart damage during obesity by inhibiting oxidative stress and endoplasmic reticulum stress

CLINICAL AND PATHOANATOMICAL PARALLELS OF THE HEART DAMAGE DUE TO COVID-19

The aim – to investigate the clinical and pathomorphological features of the heart damagein patients who died due to COVID-19 pneumonia.Materials and methods. A retrospective analysis of the medical records of 556 patients,hospitalized to Lviv Clinical Emergency Care Hospital in January- February 2021, witha diagnosis of COVID-19 pneumonia and 90 reports of pathological examination ofthe causes of death of patients with COVID-19 pneumonia was carried out. Clinicalparameters (demographic data, comorbidities, presence of COVID-19 pneumoniacomplications, complaints, medical history, results of physical examination andadditional laboratory and instrumental investigations, performed during hospitalization,including levels of NT-proBNP and troponin, determined by immunofluorescence method)and results of pathological examination were evaluated.The results. During life, most patients who died due to COVID-19 pneumonia werediagnosed with acute respiratory distress syndrome (ARDS), the development of multipleorgan failure, rarely PE. They showed significantly lower capillary blood oxygensaturation indicators compared to similar indicators of recovered patients, as well asan increase in markers of systemic inflammation (level of leukocytes and interleukin-6),fibrin degradation products (D-dimers) and markers of multiorgan failure (creatinine,NT-proBNP, troponin I). The most frequent pathomorphological signs of heartdamage in patients with COVID-19 were interstitial edema with hyperemia (63.5 %) and fragmentation of cardiomyocytes (34.1 %). Every fourth patient had mononuclear cell infiltration, which was associated with increased level of NTproBNP, oxygen saturationdecrease in capillary blood, and increase in aspartate aminotransferase. Myocardialinfarction, pericarditis, and myocarditis occurred more rarely in patients with COVID-19.Conclusions. The variety of clinical scenarios of heart damage requires a high level ofsuspicion in the early stages of the disease and the use of appropriate investigations toidentify its cause.

Cardiotoxicity and cancer care: scoping review exploring current home-based, self-management cancer care interventions

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): NHS Lothian Background/Introduction Cardiotoxicity is heart damage that occurs as consequence of some cancer treatments and drugs. Gaining a better understanding of current cancer prehabilitation and rehabilitation programmes, specifically facilitated, home-based programmes, can better illuminate how interventions can aid patients in their cancer, and possible cardiac journey. This scoping review sets out to explore the provision of multimodal, cancer prehabilitation and rehabilitation programmes available to patients. Home-based, self-management, multidimensional cancer interventions (HSMCIs) are increasing in number, due to the growing population of people living with and beyond cancer. These multimodal programmes target a range of physical and psychosocial factors to improve self-management and quality of life amongst cancer patients during prehabilitation and rehabilitation. However, preliminary searches indicate that the interventions vary significantly in their definitions of key terms, target demographics, implementation success and evidence-base. Purpose This scoping review aims to assess the nature, extent and remit of existing HSMCIs, identify their strengths, limitations, potential barriers to access and obstacles to their implementation, and clarify key terms and concepts within the field. Methods Key word searches were performed in AMED, Cochrane, PsychInfo, Medline, CINAHL and Embase databases from 2010 to 2022 to identify papers relevant to HSMCIs. Study characteristics for inclusion were home-based, multimodal, non-centre based interventions that dealt with prehabilitaton and/or rehabilitation for cancer patients, while incorporating psychological, physical and nutritional components. Results The search gleaned a total of 302 results. These results were screened independently by two investigators with a third member conducting spot checks to ensure rigor. Early findings were then cross-referenced and irrelevant papers and duplicates were removed. A total of 38 results remained that fulfilled inclusion criteria. The scoping review found that few programmes were truly multimodal taking a general approach to cancer, instead targeted one or two specific cancers. Fewer still had mention of cardiotoxicity and how to manage heart health during cancer treatment. Conclusions This scoping review has highlighted the gap for a HSMCI in care provision to cover the range of biopsychosocial support needed for those living with and beyond cancer. Consistent with earlier research it emphasises the necessity for promoting cardiovascular health in this population.

Metformin ameliorates cardiopulmonary toxicity induced by chlorpyrifos

Chlorpyrifos (CPF) is a widely used pesticide that can impair body organs. Nonetheless, metformin is known for its protective role against dysfunction at cellular and molecular levels led by inflammatory and oxidative stress. This study aimed to investigate the modulatory impacts of metformin on CPF-induced heart and lung damage. Following the treatment of Wistar rats with different combinations of metformin and CPF, plasma, as well as heart and lung tissues, were isolated to examine the level of oxidative stress biomarkers like reactive oxygen species (ROS) and malondialdehyde (MDA), inflammatory cytokines such as tumor necrosis alpha (TNF-α), high mobility group box 1 (HMGB1) gene, deoxyribonucleic acid (DNA) damage, lactate, ADP/ATP ratio, expression of relevant genes (TRADD, TERT, KL), and along with histological analysis. Based on the findings, metformin significantly modulates the impairments in heart and lung tissues induced by CPF.

Intermediate Molecular Phenotypes to Identify Genetic Markers of Anthracycline-Induced Cardiotoxicity Risk.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.

The sodium borate relieves the hypertrophic damage induced during pregnancy, it improves contractibility, reduces oxidative stress and stimulates cell proliferation

IntroductionFetal and postnatal hypertrophy develop in response to such different exposures or illnesses the mother suffers during gestation as anti-infectious and physical agents, obesity, hypertension, diabetes, and even advanced maternal age. This gives rise to high comorbidities in the newborn; therefore, looking for alternatives that contribute to cardiac homeostasis is quite necessary to inhibit the overgrowth of myocytes. Boron-derivative compounds could play a key role in exerting a repairing effect on chronic cardiac damage induced during gestation. MethodologyThe cardiotoxic effect of 6.4, 12 and 100 mg/kg of sodium tetraborate administered by oral delivery route to healthy pregnant mice was assessed. After that, the use of the chemical compound was tested in the treatment of pregnant mice previously subjected to isoproterenol (fetal hypertrophy model) on the fifth day post coitus. Prior to the sacrifice of the pups of mice an electrocardiography (ECG) was done. Morphological and histological changes of heart were assessed in newborn pups. As a damage marker, the concentration of p38 nitrogen-activated protein kinases were evaluated by using Western Blot and the levels of malondialdehyde (MDA) as well as glutathione antioxidants (GSH) and glutathione peroxidase (GPx) were tested by spectrometry. Moreover, the mRNA expression for early response genes (c-jun, c-fos y c-myc), late response (GATA-4, Mef2c, NFAT) and heart damage (ANP and BNP) was measured by qPCR real time. ResultsThe supply of 6,4 and 12 mg/kg-sodium tetraborate favored ventricular remodeling with histological alterations. By comparison, 100 mg/kg of sodium tetraborate administered during the fetal stage did not alter neither the cardiac morphology of six-week old pups nor the p38/P-p38MAPK ratio remained the same and no oxidative stress was observed.When pregnant females treated with isoproterenol were treated with 100 mg/kg sodium tetraborate during the fetal stage, an improvement in contractility was detected in the pups with an actual reduction in myocardial fibrosis and oxidative stress, but cardiac mass increased. In addition, the expression levels of c-jun, c-myc, GATA-4, MEF2c and ANP mRNA declined in comparison with CTR. However, the hypertrophic damage mechanism was sustained by c-fos, NFAT and BNP expressions. ConclusionsThe set of results achieved suggests that high concentrations of sodium tetraborate have no cardiotoxic effects. Furthermore, sodium tetraborate mitigates hypertrophy induced during pregnancy, thereby improving contractibility, reducing oxidative stress and stimulating cell proliferation. Therefore, sodium tetraborate could be an excellent prophylactic treatment administered by delivery oral route during pregnancy when there is a risk of developing fetal left ventricular hypertrophy (LVH).

Diagnosis and management of acute rheumatic fever

Acute rheumatic fever is a nonsuppurative, immune-mediated consequence of group A streptococcal pharyngitis. Recurrent or severe acute rheumatic fever can cause permanent cardiac valve damage and rheumatic heart disease. Universally, the most common major manifestations during the first episode of ARF remain carditis and arthritis. Subclinical carditis now can fulfils a major criterion for ARF in all populations as in revised Jones criteria – AHA 2015. Many of the clinical features of ARF are non-specific, so a wide range of differential diagnoses should be considered. Primary prevention requires accurate recognition and proper antibiotic treatment of GAS pharyngitis. Prevention of recurrent attacks of rheumatic fever (secondary prevention) is the most cost-effective way of preventing further rheumatic heart disease (RHD). Penicillin remains the antibiotic of choice. Intramuscular penicillin is preferred as it is more effective than oral penicillin and results in better compliance.

Mid-Regional Pro-Adrenomedullin and N-Terminal Pro-B-Type Natriuretic Peptide Measurement: A Multimarker Approach to Diagnosis and Prognosis in Acute Heart Failure.

Acute heart failure (AHF) is a major cause of hospitalization and mortality worldwide. Early and accurate diagnosis, as well as effective risk stratification, are essential for optimizing clinical management and improving patient outcomes. In this context, biomarkers have gained increasing interest in recent years as they can provide important diagnostic and prognostic information in patients with AHF. The primary objective of the present study was to compare the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-adrenomedullin (MR-proADM), and C-reactive protein (CRP) between patients diagnosed with acute heart failure (AHF) and those without AHF and sepsis. Furthermore, the study aimed to assess the diagnostic and prognostic value of the use of a multimarker approach in AHF patients. To achieve these objectives, a total of 145 patients with AHF and 127 patients without AHF and sepsis, serving as the control group, were consecutively enrolled in the study. Levels of MR-proADM (median: 2.07; (25th-75th percentiles: 1.40-3.02) vs. 1.11 (0.83-1.71) nmol/L, p < 0.0001), and NT-proBNP (5319 (1691-11,874) vs. 271 (89-931.5) pg/mL, p < 0.0001) were significantly higher in patients with AHF compared to controls, whereas CRP levels did not show significant differences. The mortality rate in the AHF group during in-hospital stay was 12%, and the rate of new re-admission for AHF within 30 days after discharge was 10%. During in-hospital follow-up, Cox regression analyses showed that levels of NT-proBNP > 10,132 pg/mL (hazard ratio (HR) 2.97; 95% confidence interval (CI): 1.13-7.82; p = 0.0284) and levels of MR-proADM > 2.8 nmol/L (HR: 8.57; CI: 2.42-30.28; p = 0.0009) predicted mortality. The combined use of MR-proADM and NT-proBNP provided significant additive predictive value for mortality and new re-admission for AHF at 30 days after discharge. A logistic regression analysis showed that the presence of NT-proBNP pg/mL > 12,973 pg mL and/or MR-proADM > 4.2 nmol/L predicted hospital re-admission within 30 days (OR: 3.23; CI: 1.05-9.91; p = 0.041). The combined assay of MR-proADM and NT-proBNP could be helpful in accurately identifying AHF and in defining prognosis and re-admission for AHF. The complementary use of these biomarkers can provide a useful clinical evaluation of AHF while also orienting clinicians to the pathophysiology underlying heart damage and assisting them in tailoring therapy.

A Novel Bromophenol Compound from Leathesia nana Inhibits Breast Cancer in a Direct Tumor Killing and Immunotherapy Manner.

Considering the resistance and toxicity of traditional chemotherapeutic drugs, seeking potential candidate for treating breast cancer effectively is a clinical problem that should be solved urgently. Natural products have attracted extensive attention, owing to their multi-target advantages and low toxicity. In the current study, the effects of XK-81, a novel bromophenol compound extracted from Leathesia nana, on breast cancer, and its underlying mechanisms, were explored. Firstly, data from in vitro experiments indicated that 4T-1, one of common mouse breast cancer cell lines, was a XK-81-susceptible cell line, and ferroptosis was the major death manner in response to XK-81 treatment, which was evidenced by increasing intracellular Fe2+ and ROS level with condensed mitochondrial membrane densities, as well as decreasing the protein expressions of SLC7A11 and GPX4. In vivo, XK-81 suppressed the growth of 4T-1 breast-tumor in both BALB/C mice and zebrafish. Obviously, XK-81 decreased the protein expression of SLC7A11 and GPX4 in tumor tissues, hinting at the occurrence of ferroptosis. Moreover, XK-81 increased CD8+ T cells and NK cells numbers and regulated M1/M2 macrophage ratio in tumor tissues, indicating XK-81's immunotherapeutic effect. Additionally, the secretions of immune-related cytokines, including TNF-α, IL-1β, and IL-12, were elevated with XK-81 stimulation in RAW 264.7 cells. Intriguingly, compared with doxorubicin-induced heart damage, XK-81 demonstrated the therapeutic advantage of little cardiotoxicity on the heart. XK-81 demonstrated potential antitumor advantage by both directly inducing ferroptosis-mediated death of tumor cells and immunization.