Endotoxemic shock is a severe complication characterized by multiple organ failure, hypotension, and impaired tissue perfusion, all contributing to high morbidity and mortality. Recent studies have highlighted the anti-inflammatory and antioxidant properties of tomentosin. This study investigates the protective effects of tomentosin against lipopolysaccharide (LPS)-induced cardiac injury and elucidates its underlying mechanisms. Mice were pre-treated with tomentosin before the LPS administration. Subsequently, cardiac injury markers, oxidative stress parameters, inflammatory mediators, and Nrf-2/NF-κB protein expression levels were analysed. The results demonstrated that tomentosin significantly reduced Troponin and CK-MB levels, alleviated oxidative stress, and suppressed inflammatory responses. Furthermore, tomentosin inhibited NF-κB activation while enhancing Nrf-2 expression. In conclusion, our findings suggest that tomentosin exerts cardioprotective effects by modulating the Nrf-2/NF-κB pathway, positioning it as a potential therapeutic candidate for preventing LPS-induced cardiac dysfunction.

Shock is a life-threatening condition characterized by inadequate tissue perfusion leading to systemic hypoxia and metabolic failure. Ischemia/reperfusion (I/R) injury exacerbates shock progression through oxidative stress and immune dysregulation, contributing to multi-organ dysfunction. This narrative review synthesizes current evidence on the interplay between I/R injury, oxidative stress, and immune modulation in shock states. We analyze the classification of shock, its progression, and the molecular pathways involved in ischemic adaptation, inflammatory responses, and oxidative injury. Shock pathophysiology is driven by systemic ischemia, triggering adaptive responses such as hypoxia-inducible factor (HIF) signaling and metabolic reprogramming. However, prolonged hypoxia leads to mitochondrial dysfunction, increased reactive oxygen species (ROS) and reactive nitrogen species (RNS) production, and immune activation. The transition from systemic inflammatory response syndrome (SIRS) to compensatory anti-inflammatory response syndrome (CARS) contributes to immune imbalance, further aggravating tissue damage. Dysregulated immune checkpoint pathways, including CTLA-4 and PD-1, fail to suppress excessive inflammation, exacerbating oxidative injury and immune exhaustion. The intricate relationship between oxidative stress, ischemia/reperfusion injury, and immune dysregulation in shock states highlights potential therapeutic targets. Strategies aimed at modulating redox homeostasis, controlling immune responses, and mitigating I/R damage may improve patient outcomes. Future research should focus on novel interventions that restore immune balance while preventing excessive oxidative injury.

Myocardial infarction (MI) is characterized by the sudden reduction in myocardial blood flow and remains the leading cause of death worldwide. Because MI causes irreversible damage to the heart, discovering drugs that can limit the extent of ischemic damage is crucial. Liensinine (LSN) is a natural alkaloid that has exhibited beneficial effects in various cardiovascular diseases, including MI; however, its molecular mechanisms of action remain largely unelucidated. In this study, we constructed murine models of MI to examine the potential beneficial effects and mechanisms of LSN in myocardial ischemic injury. Murine models of MI in wild-type and cardiomyocyte-specific β-catenin knockout mice were used to explore the role of LSN and Wnt/β-catenin signaling in MI-induced cardiac injuries and inflammatory responses. The administration of LSN markedly improved cardiac function and decreased the extent of ischemic damage and infarct size following MI. LSN not only prevented excessive inflammatory responses but also inhibited the aberrant activation of Wnt/β-catenin signaling, two factors that are critically involved in the exacerbation of MI-induced injury. Our findings provide important new mechanistic insight into the beneficial effect of LSN in MI-induced cardiac injury and suggest the therapeutic potential of LSN as a novel drug in the treatment of MI.

Cardiovascular disease (CVD) is the leading cause of death among patients with non-alcoholic fatty liver disease (NAFLD). This study investigates the association between high-sensitivity cardiac troponin (hs-cTn) levels and mortality in adults at risk of NAFLD in a representative U.S. population sample.

Among participants aged 18 years and older in the 1999-2004 National Health and Nutrition Examination Survey, we measured high-sensitivity troponin T using a single assay (Roche) and high-sensitivity troponin I using three assays (Abbott, Siemens, and Ortho). Myocardial injury was identified by elevated levels of hs-cTn. Mortality outcomes were determined through linkage with the National Death Index database, with follow-up until December 31, 2019. A multivariable Cox proportional hazards model was used to evaluate the associations between myocardial injury and mortality in the NAFLD population. Sensitivity analyses were conducted to assess the robustness of the main findings.

A total of 2581 at risk of NAFLD were included in this observational study, with myocardial injury identified in 7.01%. Over a median follow-up of 16.7 years, 937 all-cause deaths occurred, including 319 cardiovascular disease-related deaths. NAFLD individuals with myocardial injury had worse survival rates at 5, 10, and 15 years compared to those without myocardial injury. After adjusting for baseline characteristics, myocardial injury was associated with an increased risk of all-cause mortality (adjusted Hazard Ratio [aHR] 1.785, 95% CI 1.494-2.134, P < 0.001) and cardiovascular mortality (aHR 2.155, 95% CI 1.606-2.893, P < 0.001).

This large, nationally representative study demonstrates that myocardial injury, defined by elevated hs-cTn levels, is independently associated with increased all-cause and cardiovascular mortality risks in the adult population at risk of NAFLD in the United States. This association persisted after adjusting for various factors and in patients without pre-existing cardiovascular disease. The Siemens hs-cTn I assay demonstrated the strongest association with all-cause mortality. These findings highlight the potential of hs-cTn as a valuable prognostic marker in NAFLD patients, even in those without clinically apparent cardiovascular disease. Routine hs-cTn assessment may aid in risk stratification and guide targeted interventions to reduce mortality risk in this population.

Delayed reperfusion of the ischemic heart (I/R) is known to impair the recovery of cardiac function and produce a wide variety of myocardial defects, including ultrastructural damage, metabolic alterations, subcellular Ca2+-handling abnormalities, activation of proteases, and changes in cardiac gene expression. Although I/R injury has been reported to induce the formation of reactive oxygen species (ROS), inflammation, and intracellular Ca2+ overload, the generation of oxidative stress is considered to play a critical role in the development of cardiac dysfunction. Increases in the production of superoxide, hydroxyl radicals, and oxidants, such as hydrogen peroxide and hypochlorous acid, occur in hearts subjected to I/R injury. In fact, mitochondria are a major source of the excessive production of ROS in I/R hearts due to impairment in the electron transport system as well as activation of xanthine oxidase and NADPH oxidase. Nitric oxide synthase, mainly present in the endothelium, is also activated due to I/R injury, leading to the production of nitric oxide, which, upon combination with superoxide radicals, generates nitrosative stress. Alterations in cardiac function, sarcolemma, sarcoplasmic reticulum Ca2+-handling activities, mitochondrial oxidative phosphorylation, and protease activation due to I/R injury are simulated upon exposing the heart to the oxyradical-generating system (xanthine plus xanthine oxidase) or H2O2. On the other hand, the activation of endogenous antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, and the concentration of a transcription factor (Nrf2), which modulates the expression of various endogenous antioxidants, is depressed due to I/R injury in hearts. Furthermore, pretreatment of hearts with antioxidants such as catalase plus superoxide dismutase, N-acetylcysteine, and mercaptopropionylglycerine has been observed to attenuate I/R-induced subcellular Ca2+ handling and changes in Ca2+-regulatory activities; additionally, it has been found to depress protease activation and improve the recovery of cardiac function. These observations indicate that oxidative stress is intimately involved in the pathological effects of I/R injury and different antioxidants attenuate I/R-induced subcellular alterations and improve the recovery of cardiac function. Thus, we are faced with the task of developing safe and effective antioxidants as well as agents for upregulating the expression of endogenous antioxidants for the therapy of I/R injury.

As a member of the interleukin-6 family, ciliary neurotrophic factor (CNTF) regulates inflammation, oxidative stress, and other processes to exhibit neurotrophic and differentiating effects over cells in the central nervous system. It has not yet been documented, therefore, if CNTF influences the cardiac remodeling brought on by myocardial infarction (MI). The purpose of the current investigation was to identify the function and underlying mechanisms of CNTF in cardiac remodeling brought on by MI.

Using an adeno-associated virus 9 (AAV9) system and tail vein injection, we overexpressed CNTF in the hearts. To create a model of MI, C57BL/6 mice underwent left anterior descending (LAD) ligation. The following techniques were employed to assess the impact of CNTF overexpression and the underlying mechanisms: quantitative real-time PCR, western blotting, histological analysis, immunofluorescence and immunohistochemistry analysis, and echocardiography. We used H9c2 cells to confirm CNTF's in vitro effects.

In MI mice, overexpression of CNTF prevents cardiac hypertrophy and cardiac fibrosis. Furthermore, oxidative stress and ferroptosis in response to MI damage were markedly reduced by CNTF overexpression. Mechanistically, overexpression of CNTF in both in vivo and in vitro markedly enhanced PI3K/Akt signaling. However, blocking this pathway effectively negated the beneficial impact of CNTF overexpression.

Our research indicates that via initiating the PI3K/Akt signaling pathway, CNTF controls myocardial dysfunction, oxidative stress, and ferroptosis in MI-induced cardiac remodeling. CNTF may have therapeutic potential in treating MI-induced cardiac remodeling.

Myocardial infarction (MI), a severe cardiovascular condition, is typically triggered by coronary artery disease, resulting in ischemic damage and the subsequent necrosis of the myocardium. Macrophages, known for their remarkable plasticity, are capable of exhibiting a range of phenotypes and functions as they react to diverse stimuli within their local microenvironment. In recent years, there has been an increasing number of studies on the regulation of macrophage behavior based on tissue engineering strategies, and its regulatory mechanisms deserve further investigation. This review first summarizes the effects of key regulatory factors of engineered biomaterials (including bioactive molecules, conductivity, and some microenvironmental factors) on macrophage behavior, then explores specific methods for inducing macrophage behavior through tissue engineering materials to promote myocardial repair, and summarizes the role of macrophage-host cell crosstalk in regulating inflammation, vascularization, and tissue remodeling. Finally, we propose some future challenges in regulating macrophage-material interactions and tailoring personalized biomaterials to guide macrophage phenotypes.

We aimed to investigate the association between systemic inflammation and the left ventricular global function index (LVGFI) and evaluate the diagnostic performance of LVGFI for MACEs across the acute coronary syndrome (ACS) spectrum. A total of 1697 patients (794 with ST-segment elevation myocardial infarction [STEMI] and 903 with non-STEMI [NSTEMI]) were evaluated. The LVGFI was calculated using echocardiography. Inflammatory status was assessed with C-reactive protein (CRP) and the systemic immune inflammation index (SII). MACEs were defined as non-fatal re-infarction, repeated revascularization of the target vessel, and all-cause mortality at a 3-year follow-up. While the STEMI group exhibited lower LVGFI values compared with the NSTEMI group (P < .001), it had a higher SII level (P < .001) and CRP level (P = .021). The association between higher LVGFI quartiles and lower levels of systemic inflammation was more pronounced in the STEMI group. The threshold value of LVGFI to predict MACEs was <21.8% (Sensitivity = 79.2%, Specificity = 68.7%) for STEMI, while it was <25.4% (Sensitivity = 77.4%, Specificity = 70.8%) for NSTEMI. Considering both the inflammatory status and ACS spectrum when evaluating LVGFI could provide a more comprehensive assessment of cardiac function and prognosis in ACS patients.

This study aimed to investigate the protective effects and mechanisms of hyperbaric oxygen (HBO) preconditioning in a rat model of acute myocardial infarction (MI) established by ligation of the left anterior descending (LAD) coronary artery. Microarray, real-time PCR, and western blotting (WB) results demonstrated that the Mst1 gene was downregulated in the heart tissue of the MI rat model. HBO preconditioning significantly increased Mst1 expression in cardiac tissues of rats after MI modeling. Lentiviral infection was used to silence the Mst1 gene in rats treated with HBO to probe the effect of Mst1 on HBO cardioprotection. HBO preconditioning decreased heart infarct size and ameliorated cardiac function in MI rats, whereas Mst1 silencing reversed the effect of HBO administration, as indicated after heat infarct size determination via TTC staining, histological examination via HE staining, and measurements of cardiac function. HBO preconditioning reduced oxidative stress and inflammation in cardiac tissue of MI rat model, evidenced by alteration of malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), and protein carbonyl contents, as well as production of inflammation-associated myeloperoxidase (MPO), IL-1β, and TNF-α. These findings provide a new signaling mechanism through which HBO preconditioning can protect against acute MI injury through the Mst1-mediating Keap1/Nrf2/HO-1-dependent antioxidant defense system.

Myocardial infarction (MI) is a prevalent disease with high mortality rates worldwide. The course of MI is intricate and variable, necessitating personalized treatment strategies based on different mechanisms. However, variety of postoperative complications and rejections, such as heart failure, arrhythmias, cardiac rupture, and left ventricular thrombus, contribute to a poor prognosis. Despite the inclusion of antiplatelet agents and statins in the conventional treatment regimen, their clinical applicability is constrained by potential adverse effects and limited efficacy. Additionally, the mechanisms leading to MI are complex and diverse. Therefore, the development of novel compounds for MI treatment. The use of traditional Chinese medicine (TCM) in the prevention and treatment of cardiovascular diseases, including MI, is grounded in its profound historical background, comprehensive theoretical system, and accumulated knowledge. An increasing number of contemporary evidence-based medical studies have demonstrated that TCM plays a significant role in alleviating symptoms and improving the quality of life for MI patients. Chinese herbal formulations and active ingredients can intervene in the pathological process of MI through key factors such as inflammation, oxidative stress, apoptosis, ferroptosis, pyroptosis, myocardial fibrosis, angiogenesis, and autophagy. This article critically reviews existing herbal formulations from an evidence-based medicine perspective, evaluating their research status and potential clinical applications. Additionally, it explores recent advancements in the use of herbal medicines and their components for the prevention and treatment of MI, offering detailed insights into their mechanisms of action.

Polygonum plebeium, a member of the Polygonaceae family, is commonly known as small knotweed and has been traditionally used to treat various ailments, including cough, gastrointestinal disorders, respiratory infections, liver disease, inflammation, dysentery, eczema and ringworms, and other skin conditions. Many studies have suggested that plants belonging to this genus possess strong cardio-protective potentials. Rats were pre-treated with crude methanolic extract and other fractions at a dose of 500 mg/kg followed by administration of Isoproterenol hydrochloride after 24 h for 2 days. The cardioprotective effect was determined by investigating the levels of Biomarkers responsible for myocardial infarction (MI). Among all fractions Pp.CF (chloroform fraction) exhibited a significant cardioprotective effect by decreasing the levels of ALT, AST, CPK, and LDH to 74.56 ± 1.45, 95.78 ± 2.75, 156.73 ± 1.84, and 215.55 ± 5.33 IU/L in serum. The same fraction was tested for cardio-protective potential at a dose of 50, 100, and 250 mg/kg. Pp.CF at a dose of 250 mg/kg exhibited prominent effects and reduced levels of biomarkers responsible for MI. Further investigations confirmed that Pp.CF possesses antihyperlipidemic, membrane stabilizing, and thrombolytic potential which suggests P. plebeium an ideal candidate for natural product isolation which will be helpful in the management of cardiovascular problems.

Citrus peel essential oils (CPEOs) have demonstrated substantial medicinal potential for glioblastoma treatment because of their extensive antitumor effects, low potential for drug resistance, and ability to cross the human blood-brain barrier. In this study, the chemical compositions of five CPEOs were analyzed via gas chromatography-mass spectrometry (GC-MS). CCK8 assays were used to evaluate the ability of five CPEOs to inhibit U251 human glioblastoma cells, and XLB and RA were selected for further investigation. Through wound healing assays and cell cycle and apoptosis analyses via flow cytometry, it was revealed that these CPEOs inhibited cell migration, arrested the cell cycle at G1/G0, and induced apoptosis with similar levels of inhibition. After CPEOs treatment, the intracellular Ca2+ content and reactive oxygen species levels in U251 cells increased significantly, whereas the mitochondrial membrane potential decreased. Additionally, the antioxidant enzyme system (SOD, POD, CAT, and GR) and the nonenzymatic defense system (GSH) were inhibited, leading to an increase in lipid peroxidation. qRT-PCR indicated the significant upregulation of intracellular calcium ion signaling pathways and the upregulation of mitochondrial apoptosis-related genes. Additionally, the activation of calcicoptosis-related indicators induced by the CPEOs could be reversed by inhibitor treatment, confirming that both of the selected CPEOs inhibit tumors by activating calcicoptosis-related pathways. These findings highlight the immense potential of CPEOs in healthcare and pharmaceutical applications by not only providing a scientific basis for the potential application of CPEOs in the treatment of glioblastoma but also offering new insights for the development of novel antitumor drugs.

Myocardial infarction (MI) is an important factor inducing mortality globally. Apoptosis and oxidative stress have been identified as major drivers for MI development. Anti-apoptosis therapies exhibit promising effects in protecting against MI. Typically, Taohong Siwu Decoction (THSWD) exerts cardioprotective properties. However, whether THSWD suppresses oxidative stress-induced myocardial apoptosis after MI and the associated mechanisms remain unclear.

The present work focused on examining the protective effects of THSWD on oxidative stress-induced myocardial apoptosis after MI and its possible mechanisms.

The MI mouse model was established via left anterior descending coronary artery (LAD) ligation. Thereafter, echocardiography and histopathology were performed to examine the cardioprotective effects of THSWD. Meanwhile, the protective potential of THSWD against myocardial apoptosis and oxidative stress, as well as modulation of phosphatase and tensin homolog (PTEN) pathway in MI were investigated through TUNEL staining, ROS analysis, immunohistochemistry (IHC), Western blot (WB) and oxidative stress-related biochemical enzyme assay, respectively. Further, the apoptosis of neonatal cardiomyocytes (NCMs) and H9C2 cells was induced by TBHP in vitro. Thereafter, the impacts of THSWD on the TBHP-induced H9C2 and NCMs were detected by Hoechst33342/PI fluorescent staining, WB, ROS analysis, and oxidative stress-related biochemical enzyme assay. In addition, PTEN was overexpressed using transfection viruses in vivo and in vitro for further investigation.

THSWD might inhibit PTEN and promote the PI3K/AKT pathway in MI mice to prevent myocardial apoptosis. In vitro, THSWD prevented the TBHP-induced apoptosis of NCMs and H9C2 cells. This was achieved by blocking PTEN activity and regulating PI3K/AKT pathway. Moreover, PTEN overexpression significantly enhanced the TBHP-induced H9C2 apoptosis and oxidative stress-induced myocardial apoptosis after MI, and partially blocked the protection of THSWD against myocardial apoptosis and modulating PI3K/AKT pathway in vitro and in vivo.

THSWD suppressed oxidative stress-induced myocardial apoptosis in vitro and in vivo by inhibiting PTEN pathway.

Increased life expectancy, attributed to improved access to healthcare and drug development, has led to an increase in multimorbidity, a key contributor to polypharmacy. Polypharmacy is characterised by its association with a variety of adverse events in the older persons. The mechanisms involved in the development of age-related chronic diseases are largely unknown; however, altered redox homeostasis due to ageing is one of the main theories. In this context, the present review explores the development and interaction between different age-related diseases, mainly linked by oxidative stress. In addition, drug interactions in the treatment of various diseases are described, emphasising that the holistic management of older people and their pathologies should prevail over the individual treatment of each condition.

After myocardial infarction (MI), ventricular dilation and the microscopic passive stretching of the infarcted border zone is the meaning contributor to the continuous expansion of myocardial fibrosis. Epicardial hydrogel patches have been demonstrated to alleviate this sequela of MI in small-animal models. However, these have not been successfully translated to humans or even large animals, in part because of challenges in attaining both the greater stiffness and slower viscoelastic relaxation that mathematical models predict to be optimal for application to larger, slower-beating hearts. Here, using borate-based dynamic covalent chemistry, we develop an injectable "heart rate matched" viscoelastic gelatin (VGtn) hydrogel with a gel point tunable across the stiffnesses and frequencies that are predicted to transspecies and cross-scale cardiac repair after MI. Small-animal experiments demonstrated that, compared to heart rate mismatched patches, the heart rate matched VGtn patches inhibited ventricular bulging and attenuated stress concentrations in the myocardium after MI. In particular, the viscoelastic patch can coordinate the microscopic strain at the infarction boundary. VGtn loaded with anti-fibrotic agents further reduced myocardial damage and promoted angiogenesis in the myocardium. The tuned heart rate matched patches demonstrated similar benefits in a larger-scale and lower heart rate porcine MI model. Results suggest that heart rate matched VGtn patches may hold potential for clinical translation.

The effect of methylprotodioscin (MPD), a steroidal saponin obtained from medicinal plants, on myocardial infarction (MI) remains elusive. In this study, HL-1 and AC16 cells were subjected to injury induced by hypoxic environment, and a mouse model of MI was established by ligating the left anterior descending. MPD significantly increased viabilities and proliferations, improved the stability of MMP, reduced ROS and inflammatory factor levels in hypoxia cardiomyocytes. Moreover, MPD significantly improved cardiac functions, increased the ventricular ejection fraction and short axis shortening rate of mice with MI, reduced the infarction area, alleviated oxidative stress and increased ATPase activities. Then, differentially expressed proteins (DEPs) were discovered and evaluated using tandem mass tag (TMT)-based proteomics and bioinformatics approaches. Compared with sham group, there were 420 DEPs in the cardiac tissue of MI group, likewise, 163 DEPs in MPD group were identified compared to MI group. By validating, the expression of COX6C was elevated in MI group and declined in MPD groups, consistent with the TMT-based proteomics results. Correspondingly, p-NF-κB expression was downregulated, while Nrf2 and SOD expressions were upregulated by MPD. Moreover, si-COX6C transfection blocked the regulatory effects of MPD on COX6C-mediated inflammation and oxidative stress in MI. Our findings indicate that MPD, a naturally occurring active ingredient, could effectively improve cardiac function. Its ability may result from regulating COX6C to reduce oxidative stress and suppress inflammation, suggesting that MPD is very attractive for the treatment of MI.

Myocardial infarction (MI) is the primary source of death in cardiovascular diseases. Myricitrin (MYR) is a phenolic compound known for its antioxidant properties. This study aimed to investigate the impact of MYR alone or combined with exercise on a rat model of MI and its underlying mechanism. Sprague-Dawley rats were randomized into 5 groups: sham-operated (Sham), MI-sedentary (MI-Sed), MI-exercise (MI-Ex), MI-sedentary + MYR (MI-Sed-MYR) and MI-exercise + MYR (MI-Ex-MYR). MI was induced through ligation of left anterior descending coronary artery. The treatment with exercise or MYR (30 mg/kg/d) gavage began one week after surgery, either individually or in combination. After 8 weeks, the rats were assessed for cardiac function. Myocardial injuries were estimated using triphenyltetrazolium chloride, sirius red and Masson staining. Changes in reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), apoptosis and Nrf2/HO-1 pathway were analyzed by ROS kit, JC-1 kit, TUNEL assay, Western blot and immunohistochemistry. Both MYR and exercise treatments improved cardiac function, reduced infarct size, suppressed collagen deposition, and decreased myocardial fibrosis. Additionally, both MYR and exercise treatments lowered ROS production induced by MI, restored ΔΨm, and attenuated oxidative stress and apoptosis in cardiomyocytes. Importantly, the combination of MYR and exercise showed greater efficacy compared to individual treatments. Mechanistically, the combined intervention activated the Nrf2/HO-1 signaling pathway. These findings suggest that the synergistic effect of MYR and exercise may offer a promising therapeutic approach for alleviating MI.

A growing interest in using Nigella sativa oil (NSO) in the prevention or treatment of several cardiovascular diseases has prompted this study. The research aims to investigate the effect of NSO on cardiac damage prevention after long-term administration in induced myocardial infarction (MI) in rats.

NSO was analyzed for its fatty acids composition using gas chromatography-mass spectrometry (GC-MS) analysis and administered in rats before and after isoproterenol (45 mg/kg body weight) induced myocardial infarction. The following parameters were assessed: electrocardiograms, histopathological examination, serum biochemical aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase-myocardial band (CK-MB), serum and heart inflammation (tumor necrosis factor-alpha (TNF), interleukin 1 beta (IL-1b), and interleukin 6 (IL-6)), and tissue oxidative stress (total antioxidant capacity (TAC), total oxidative stress (TOS), nitric oxide (NO), malondialdehyde (MDA), and the total thiols (THIOL)).

Linoleic acid (C18:2n-6) and oleic acid (C18:1n-9) were approximately 89% of total fatty acids while palmitic acid (C16:0) was 6.10%. Administration of NSO for 28 days helped in preventing QT and QTc interval prolongation and reduced heart rate (HR), after MI induction. The histological assessment showed improvement in myofibrillary degeneration and necrosis and also better reduced inflammatory process in the groups treated with NSO. In serum, pro-inflammatory cytokines IL-1b and IL-6 were downregulated in chronic conditions (for IL-1b, NSO vs. control was 86.09vs 150.39 pg/mL, and for IL-6 NSO vs. control was 78.00 vs. 184.98 pg/ml). In the heart tissue, the downregulation was observed only for TNF in both acute and chronic conditions (acute NSO vs. control was 132.37 vs. 207.63 pg/mL, and chronic NSO vs. control was 135.83 vs. 183.29 pg/ml). The pro-oxidant parameters TOS, NO, MDA, and OSI, were reduced in the groups treated with NSO only after 14 days of treatment, suggesting that the NSO antioxidant effect is time-dependent.

NSO administration might have a favourable impact on the regulation of oxidative stress and inflammation processes after MI induction in rats, and it is worth considering its administration as an adjuvant treatment.

Ischemic heart disease (IHD) is a common clinical cardiovascular disease with high morbidity and mortality. Sodium glucose cotransporter protein inhibitor (SGLTi) is a novel hypoglycemic drug. To date, both clinical trials and animal experiments have shown that SGLTi play a protective role in IHD, including myocardial infarction (MI) and ischemia/reperfusion (I/R). The protective effects may be involved in mechanisms of energy metabolic conversion, anti-inflammation, anti-fibrosis, ionic homeostasis improvement, immune cell development, angiogenesis and functional regulation, gut microbiota regulation, and epicardial lipids. Thus, this review summarizes the above mechanisms and aims to provide theoretical evidence for therapeutic strategies for IHD.

Vitamins are known to affect the regulation of several biochemical and metabolic pathways that influence cellular function. Adequate amounts of both hydrophilic and lipophilic vitamins are required for maintaining normal cardiac and vascular function, but their deficiencies can contribute to cardiovascular abnormalities. In this regard, a deficiency in the lipophilic vitamins, such as vitamins A, D, and E, as well as in the hydrophilic vitamins, such as vitamin C and B, has been associated with suboptimal cardiovascular function, whereas additional intakes have been suggested to reduce the risk of atherosclerosis, hypertension, ischemic heart disease, arrhythmias, and heart failure. Here, we have attempted to describe the association between low vitamin status and cardiovascular disease, and to offer a discussion on the efficacy of vitamins. While there are inconsistencies in the impact of a deficiency in vitamins on the development of cardiovascular disease and the benefits associated with supplementation, this review proposes that specific vitamins may contribute to the prevention of cardiovascular disease in individuals at risk rather than serve as an adjunct therapy.

Myocardial infarction (MI) is a common type of cardiovascular disease. The incidence of ventricular remodeling dysplasia and heart failure increases significantly after MI. The objective of this study is to investigate whether erythropoietin hepatocellular receptor B2 (EPHB2) can regulate myocardial injury after MI and explore its regulatory pathways. EPHB2 is significantly overexpressed in the heart tissues of MI mice. The downregulation of EPHB2 alleviates the cardiac function damage after MI. Knockdown EPHB2 alleviates MI-induced myocardial tissue inflammation and apoptosis, and myocardial fibrosis in mice. EPHB2 knockdown significantly inhibits the activation of mitogen activated kinase-like protein (MAPK) pathway in MI mice. Moreover, EPHB2 overexpression significantly promotes the phosphorylation of MAPK pathway-related protein, which can be reversed by MAPK-IN-1 (an MAPK inhibitor) treatment. In conclusion, silencing EPHB2 can mitigate MI-induced myocardial injury by inhibiting MAPK signaling in mice, suggesting that targeting EPHB2 can be a promising therapeutic target for MI-induced myocardial injury.

The role of intravenous immunoglobulin in protecting the diabetic heart from ischemia/reperfusion (I/R) injury is unclear. Hearts isolated from adult diabetic and nondiabetic Wistar rats (n = 8 per group) were treated with intravenous immunoglobulin (IVIG) either 2 hours before euthanasia, before ischemia, or at reperfusion. Hemodynamic data were acquired using the Isoheart software version 1.524-S. Ischemia/reperfusion (I/R) injury was evaluated by 2,3,5-triphenyltetrazolium chloride staining and troponin T levels. The levels of apoptosis markers, caspases-3/8, antioxidant enzymes, superoxide dismutase and catalase, glucose transporters, GLUT-1 and GLUT-4, phosphorylated ERK1/2, and phosphorylated eNOS were estimated by Western blotting. Proinflammatory and anti-inflammatory cytokine levels were evaluated using enzyme-linked immunosorbent assays. Intravenous immunoglobulin administration abolished the effects of I/R injury in hearts subjected to hyperglycemia when infused at reperfusion, before ischemia, or at reperfusion in 4-week diabetic rat hearts and only at reperfusion in 6-week diabetic rat hearts. IVIG infusion resulted in a significant (P < 0.05) recovery of cardiac hemodynamics and decreased infarct size. IVIG also reduced the levels of troponin T, apoptotic enzymes, and proinflammatory cytokines. IVIG significantly (P < 0.05) increased the levels of anti-inflammatory cytokines, antioxidant enzymes, GLUT-4, and phosphorylated eNOS. Intravenous immunoglobulin protected the hearts from I/R injury if infused at reperfusion in the presence of hyperglycemia, in 4- and 6-week diabetic rat hearts, and when infused before ischemia in 4-week diabetic rat hearts. IVIG exerts its cardioprotective effects associated with the upregulated phosphorylated eNOS/GLUT-4 pathway.

The thymus, a central lymphoid organ in animals, serves as the site for T cell development, differentiation and maturation, vital to adaptive immunity. The thymus is critical for maintaining tissue homeostasis to protect against tumors and tissue damage. An overactive or prolonged immune response can lead to oxidative stress from increased production of reactive oxygen species. Heat stress induces oxidative stress and overwhelms the natural antioxidant defense mechanisms. This study's objectives were to investigate the protective properties of astaxanthin against heat-induced oxidative stress and apoptosis in the chicken thymus, by comparing the growth performance and gene signaling pathways among three groups: thermal neutral, heat stress, and heat stress with astaxanthin. The thermal neutral temperature was 21-22 °C, and the heat stress temperature was 32-35 °C. Both heat stress groups experienced reduced growth performance, while the astaxanthin-treated group showed a slightly lesser decline. The inflammatory response and antioxidant defense system were activated by the upregulation of the NF-kB, NFE2L2, PPARα, cytoprotective capacity, and apoptotic gene pathways during heat stress compared to the thermal neutral group. However, expression levels showed no significant differences between the thermal neutral and heat stress with antioxidant groups, suggesting that astaxanthin may mitigate inflammation and oxidative stress damage.

Acute pancreatitis (AP) is a common inflammatory disorder of the exocrine pancreas that causes severe morbidity and mortality. Although the pathophysiology of AP is poorly understood, a substantial body of evidence suggests some critical events for this disease, such as dysregulation of digestive enzyme production, cytoplasmic vacuolization, acinar cell death, edema formation, and inflammatory cell infiltration into the pancreas. Oxidative stress plays a role in the acute inflammatory response. The present review clarified the role of oxidative stress in the occurrence and development of AP by introducing oxidative stress to disrupt cellular Ca2+ balance and stimulating transcription factor activation and excessive release of inflammatory mediators for the application of antioxidant adjuvant therapy in the treatment of AP.

Acute liver and kidney injury is the most common complication after aortic surgery, which seriously affects the survival and safety of perioperative patients. The presence of chronic preoperative liver and renal insufficiency, presence of preoperative blood inflammation indicators, duration of intraoperative extracorporeal circulation, and volume of red blood cell transfusion are the main influencing factors for acute postoperative liver and kidney injuries. In recent years, with the research progress on oxidative stress, a growing body of evidence has demonstrated that oxidative stress may cause tissue damage after ischemia-reperfusion (IR). However, the impact of the oxidative stress of distal tissues caused by IR on liver and renal cells after arterial surgeries has not yet been elucidated.

New Zealand white rabbits were used for the experiments and were divided into three groups. Among them, two groups were fed high-fat feed to establish a white rabbit model of hypertriglyceridemia, whereas the control group was provided with ordinary feed. In the experiment, white rabbits were subjected to occlusion of the infrarenal aorta abdominalis to simulate IR of the lower limbs. The effects of high triglyceride levels after the arterial IR of the lower limbs were investigated using the contents of reactive oxygen species (ROS) and malondialdehyde (MDA), a fat metabolite, in ischemic muscle tissues and blood tissues. One of the groups receiving high-fat feed received intervention with reduced glutathione (GSH) before IR of the lower limbs. Pathological studies were performed to identify the expression levels of inflammatory factors and inflammatory cells in liver and renal cells as well as cell apoptosis. The effects of GSH administration before IR on reducing the oxidative stress in adipose tissues and alleviating liver and kidney damage after stress response were investigated.

After IR, the increases in ROS and MDA in ischemic muscle tissues and blood tissues were higher in white rabbits with high triglyceride levels than in those that only received ordinary feed or received intervention with GSH. In addition, for white rabbits with high triglyceride levels, the TNF-α expression levels in the liver increased after IR. Moreover, a considerable increase in the expression of TNF-α, IL-6, macrophages, and T lymphocytes were observed in renal cells. A large number of inflammatory cells and the formation of immune complexes were also noted in the glomeruli; in addition, cell apoptosis was promoted.

This study showed that high triglyceride levels enhanced the oxidative stress response and increased ROS production in New Zealand white rabbits after arterial IR of the lower limbs. High ROS levels activated the expression of inflammatory factors and inflammatory cells in the liver and kidney, which affected cell functions and promoted apoptosis. At high triglyceride levels, GSH downregulated ROS production in oxidative stress after IR, thereby protecting liver and kidney functions.

Myocardial infarction (MI) -induced cardiac dysfunction can be attenuated by aerobic exercises. This study explored the mechanism of interval training (IT) regulating cardiac function in MI rats, providing some theoretical basis for clarifying MI pathogenesis and new ideas for clinically treating MI.

Rats were subjected to MI modeling, IT intervention, and treatments of the Transforming growth factor-β1 (TGF-β1) pathway or the nod-like receptor protein 3 (NLRP3) activators. Cardiac function and hemodynamic indicator alterations were observed. Myocardial pathological damage and fibrosis, reactive oxygen species (ROS) level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities, MDA content, inflammasome-associated protein levels, and inflammatory factor levels were assessed. The binding between TGF-β1 and receptor was detected.

MI rats exhibited decreased left ventricle ejection fraction (LVEF), left ventricle fractional shortening  (LVFS), left ventricular systolic pressure  (LVSP), positive and negative derivates max/min (dP/dt max/min) and increased left ventricular end-systolic pressure (LVEDP), a large number of scar areas in myocardium, disordered cell arrangement and extensive fibrotic lesions, increased TGF-β1 and receptor binding, elevated ROS level and MDA content and weakened SOD, CAT and GSH-Px activities, and up-regulated NLRP3, apoptosis-associated speck-like protein containing a CARD  (ASC) and cleaved-caspase-1 levels, while IT intervention caused ameliorated cardiac function. IT inactivated the TGF-β1 pathway to decrease oxidative stress in myocardial tissues of MI rats and inhibit NLRP3 inflammasome activation. Activating NLRP3 partially reversed IT-mediated improvement on cardiac function in MI rats.

IT diminished oxidative stress in myocardial tissues and suppressed NLRP3 inflammasome activation via inactivating the TGF-β1 pathway, thus improving the cardiac function of MI rats.

Rap1 GTPase-activating protein (Rap1GAP) is an important tumor suppressor. The purpose of this study was to investigate the role of Rap1GAP in myocardial infarction (MI) and its potential mechanism. Left anterior descending coronary artery ligation was performed on cardiac-specific Rap1GAP conditional knockout (Rap1GAP-CKO) mice and control mice with MI. Seven days after MI, Rap1GAP expression in the hearts of control mice peaked, the expression of proapoptotic markers (Bax and cleaved caspase-3) increased, the expression of antiapoptotic factors (Bcl-2) decreased, and the expression of the inflammatory factors IL-6 and TNF-α increased; thus, apoptosis occurred, inflammation, infarct size, and left ventricular dysfunction increased, while the heart changes caused by MI were alleviated in Rap1GAP-CKO mice. Mouse heart tissue was obtained for transcriptome sequencing, and gene set enrichment analysis (GSEA) was used to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. We found that Rap1GAP was associated with the AMPK and NF-κB signaling pathways and that Rap1GAP inhibited AMPK/SIRT1 and activated the NF-κB signaling pathway in model animals. Similar results were observed in primary rat myocardial cells subjected to oxygen-glucose deprivation (OGD) to induce ischemia and hypoxia. Activating AMPK with the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) reversed the damage caused by Rap1GAP overexpression in cardiomyocytes. In addition, the coimmunoprecipitation results showed that exogenous Rap1GAP interacted with AMPK. Rap1GAP was verified to regulate the AMPK SIRT1/NF-κB signaling pathway and exacerbate the damage to myocardial cells caused by ischemia and hypoxia. In conclusion, our results suggest that Rap1GAP promotes MI by modulating the AMPK/SIRT1/NF-κB signaling pathway and that Rap1GAP may be a therapeutic target for MI treatment in the future.

Myocardial ischemia-reperfusion (I/R) injury is a pathogenic mechanism of myocardial infarction and heart failure, constituting a major health concern globally. Diannexin is a homodimer of recombinant human annexin V and elicits important roles in several I/R injuries. Nevertheless, its function in MI/R remains elusive. Here, Diannexin alleviated simulated I/R (SI/R)-induced cardiomyocyte death and oxidative injury by increasing cell viability and inhibiting cell apoptosis, ROS, lactate dehydrogenase, malondialdehyde production and anti-oxidative SOD activity. Diannexin inhibited SI/R-induced expression of fibrotic protein collagen I and collagen III. Furthermore, Diannexin suppressed LPS-induced macrophage polarization towards pro-inflammatory M1-like phenotype and enhanced IL-4-evoked anti-inflammatory M2 polarization. Concomitantly, Diannexin inhibited SI/R exposure-induced macrophage polarization to M1 subtypes. Importantly, conditioned medium (CM) from SI/R-stimulated macrophages evoked cardiomyocyte apoptosis, which was reversed when cells were co-cultured with CM from Diannexin-treated macrophages under SI/R conditions. Mechanically, the activation of TLR4/NF-κB/NLRP3 inflammasome signaling in SI/R-treated cells was mitigated by Diannexin. Reactivating this pathway antagonized the protective effects of Diannexin on SI/R-induced cardiomyocyte oxidative injury, fibrotic protein expression and macrophage polarization and M1 macrophage-induced apoptosis of cardiomyocytes. In vivo, Diannexin alleviated abnormal cardiac structure, dysfunction and collagen position in MI/R mice. Additionally, Diannexin reduced M1-polarized and elevated M2-polarized macrophages in heart tissues at five days post-MI/R. The activation of TLR4/NF-κB/NLRP3 inflammasome pathway in MI/R mice was attenuated after Diannexin administration. Together, Diannexin may alleviate the development of MI/R injury by directly regulating cardiomyocyte oxidative injury, fibrotic potential and indirectly affecting macrophage polarization-mediated cardiomyocyte apoptosis, indicating a promising therapeutic strategy for MI/R.

Purpose: This study aimed to assess the efficacy and safety of Panax notoginseng saponin (PNS) injection, when combined with conventional treatment (CT), for acute myocardial infarction (AMI). Methods: Comprehensive searches were conducted in seven databases from inception until 28 September 2023. The search aimed to identify relevant randomized controlled trials (RCTs) focusing on PNS injection in the context of AMI. This meta-analysis adhered to the PRISMA 2020 guidelines, and its protocol was registered with PROSPERO (number: CRD42023480131). Result: Twenty RCTs involving 1,881 patients were included. The meta-analysis revealed that PNS injection, used adjunctively with CT, significantly improved treatment outcomes compared to CT alone, as evidenced by the following points: (1) enhanced total effective rate [OR = 3.09, p < 0.05]; (2) decreased incidence of major adverse cardiac events [OR = 0.32, p < 0.05]; (3) reduction in myocardial infarct size [MD = -6.53, p < 0.05]; (4) lower ST segment elevation amplitude [MD = -0.48, p < 0.05]; (5) mitigated myocardial injury as indicated by decreased levels of creatine kinase isoenzymes [MD = -11.19, p < 0.05], cardiac troponin T [MD = -3.01, p < 0.05], and cardiac troponin I [MD = -10.72, p < 0.05]; (6) enhanced cardiac function, reflected in improved brain natriuretic peptide [MD = -91.57, p < 0.05], left ventricular ejection fraction [MD = 5.91, p < 0.05], left ventricular end-diastolic dimension [MD = -3.08, p < 0.05], and cardiac output [MD = 0.53, p < 0.05]; (7) reduced inflammatory response, as shown by lower levels of C-reactive protein [MD = -2.99, p < 0.05], tumor necrosis factor-α [MD = -6.47, p < 0.05], interleukin-6 [MD = -24.46, p < 0.05], and pentraxin-3 [MD = -2.26, p < 0.05]; (8) improved vascular endothelial function, demonstrated by decreased endothelin-1 [MD = -20.56, p < 0.05] and increased nitric oxide [MD = 1.33, p < 0.05]; (9) alleviated oxidative stress, evidenced by increased superoxide dismutase levels [MD = 25.84, p < 0.05]; (10) no significant difference in adverse events [OR = 1.00, p = 1.00]. Conclusion: This study highlighted the efficacy and safety of adjunctive PNS injections in enhancing AMI patient outcomes beyond CT alone. Future RCTs need to solidify these findings through rigorous methods. Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO/), identifier (CRD42023480131).

The senescence process is associated with accumulated oxidative damage and increased metal concentration in the heart and brain. Besides, abnormal metal-protein interactions have also been linked with the development of several conditions, including Alzheimer's and Parkinson's diseases. Over the years we have described a series of structure-related compounds with different activities towards models of such diseases. In this work, we evaluated the potential of three N-acylhydrazones (INHHQ: 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone, HPCIH: pyridine-2-carboxaldehyde isonicotinoyl hydrazone and X1INH: 1-methyl-1H-imidazole-2-carboxaldehyde isonicotinoyl hydrazone) to prevent oxidative stress in cellular models, with the dual intent of being active on this pathway and also to confirm their lack of cardiotoxicity as an important step in the drug development process, especially considering that the target population often presents cardiovascular comorbidity. The 8-hydroxyquinoline-contaning compound, INHHQ, exhibits a significant cardioprotective effect against hydrogen peroxide and a robust antioxidant activity. However, this compound is the most toxic to the studied cell models and seems to induce oxidative damage on its own. Interestingly, although not possessing a phenol group in its structure, the new-generation 1-methylimidazole derivative X1INH showed a cardioprotective tendency towards H9c2 cells, demonstrating the importance of attaining a compromise between activity and intrinsic cytotoxicity when developing a drug candidate.

In order to determine the behavior of the right ventricle, we have reviewed the existing literature in the area of cardiac remodeling, signal transduction pathways, subcellular mechanisms, β-adrenoreceptor-adenylyl cyclase system and myocardial catecholamine content during the development of left ventricular failure due to myocardial infarction. The right ventricle exhibited adaptive cardiac hypertrophy due to increases in different signal transduction pathways involving the activation of protein kinase C, phospholipase C and protein kinase A systems by elevated levels of vasoactive hormones such as catecholamines and angiotensin II in the circulation at early and moderate stages of heart failure. An increase in the sarcoplasmic reticulum Ca2+ transport without any changes in myofibrillar Ca2+-stimulated ATPase was observed in the right ventricle at early and moderate stages of heart failure. On the other hand, the right ventricle showed maladaptive cardiac hypertrophy at the severe stages of heart failure due to myocardial infarction. The upregulation and downregulation of β-adrenoreceptor-mediated signal transduction pathways were observed in the right ventricle at moderate and late stages of heart failure, respectively. The catalytic activity of adenylate cyclase, as well as the regulation of this enzyme by Gs proteins, were seen to be augmented in the hypertrophied right ventricle at early, moderate and severe stages of heart failure. Furthermore, catecholamine stores and catecholamine uptake in the right ventricle were also affected as a consequence of changes in the sympathetic nervous system at different stages of heart failure. It is suggested that the hypertrophied right ventricle may serve as a compensatory mechanism to the left ventricle during the development of early and moderate stages of heart failure.

When exposed to oxidative and electrophilic stress, a protective antioxidant response is initiated by nuclear factor erythroid 2-related factor 2 (Nrf2). However, the extent of its importance in the forensic diagnosis of acute ischemic heart diseases (AIHD), such as myocardial infarction (MI), remains uncertain. On the other hand, immunohistochemical analyses of fibronectin (FN) and the terminal complement complex (C5b-9) prove valuable in identifying myocardial ischemia that precedes necrosis during the postmortem diagnosis of sudden cardiac death (SCD). In this study, we investigated the immunohistochemical levels of Nrf2, FN, and C5b-9 in human cardiac samples to explore their forensic relevance for the identification of acute cardiac ischemia. Heart samples were obtained from 25 AIHD cases and 39 non-AIHD cases as controls. Nrf2 was localized in the nuclei of cardiomyocytes, while FN and C5b-9 were detected in the myocardial cytoplasm. The number of intranuclear Nrf2 positive signals in cardiomyocytes increased in AIHD cases compared to control cases. Additionally, the grading of positive portions of cardiac FN and C5b-9 in the myocardium was also significantly enhanced in AIHD, compared to controls. Collectively, these results indicate that the immunohistochemical investigation of Nrf2 combined with FN, and/or C5b-9 holds the potential for identifying early-stage myocardial ischemic lesions in cases of SCD.

Fumaria indica (Hausskn.) Pugsley (FIP), a member of the Papaveraceae family, has a documented history of use in traditional medicine to treat cardiovascular ailments, particularly hypertension, and has shown substantial therapeutic efficacy among native cultures worldwide. However, the identification of bioactive compounds and the mechanism of hypotensive effect with the cardioprotective potential investigations are yet to be determined. The study aimed to identify bioactive compounds, explore the hypotensive mechanism and cardioprotective potential, and assess the safety of Fumaria indica (Hausskn.) Pugsley hydromethanolic extract (Fip.Cr). LC ESI-MS/MS analysis was performed to identify the bioactive compounds. In vitro experiments were conducted on isolated rat aorta and atria, and an in vivo invasive BP measurement model was used. Acute and subacute toxicities were assessed for 14 and 28 days, respectively. Isoproterenol (ISO) was used to develop the rats' myocardial infarction damage model. The mRNA levels of NLRP3 inflammasome and the abundance level of Firmicutes and Lactobacillus were measured by qRT-PCR. The hypotensive effect of FIP bioactive compounds was also investigated using in silico methods. Fip. Cr LC ESI-MS/MS analysis discovered 33 bioactive compounds, including alkaloids and flavonoids. In isolated rat aorta, Fip.Cr reversed contractions induced by K+ (80 mM), demonstrating a calcium entry-blocking function, and had a vasorelaxant impact on phenylephrine (PE) (1 μM)-induced contractions unaffected by L-NAME, ruling out endothelial NO participation. Fip.Cr caused negative chronotropic and inotropic effects in isolated rat atria unaffected by atropine pretreatment, eliminating cardiac muscarinic receptor involvement. Safety evaluation showed no major adverse effects. In vivo, invasive BP measurement demonstrated a hypotensive effect comparable to verapamil. Fip.Cr protected the rats from ISO-induced MI interventions significantly in biometrical and cardiac serum biochemical indicators and histological examinations by reducing inflammation via inhibiting NLRP3 inflammasome and elevating Firmicutes and Lactobacillus levels. The network pharmacology study revealed that the FIP hypotensive mechanism might involve MMP9, JAK2, HMOX1, NOS2, NOS3, TEK, SERPINE1, CCL2, and VEGFA. The molecular docking study revealed that FIP bioactive compounds docked better with CAC1C_ HUMAN than verapamil. These findings demonstrated that Fip.Cr's hypotensive mechanism may include calcium channel blocker activity. Fip.Cr ameliorated ISO-induced myocardial infarction in rats by attenuating inflammation, which might be via inhibiting NLRP3 inflammasome and may prove beneficial for treating MI.

Introduction: Corydalis yanhusuo total alkaloids (CYTA) are the primary active ingredients in yanhusuo, known for their analgesic and cardioprotective effects. However, the mechanisms underlying the treatment of Myocardial ischemia (MI) with CYTA have not been reported. The purpose of this study was to explore the protective effect of CYTA on MI and its related mechanisms. Methods: A network pharmacology was employed to shed light on the targets and mechanisms of CYTA's action on MI. The protective effect of CYTA against hypoxia damage was evaluated in H9c2 cells. Furthermore, the effects of CYTA on L-type Ca2+ current (ICa-L), contractile force, and Ca2+ transient in cardiomyocytes isolated from rats were investigated using the patch clamp technique and IonOptix system. The network pharmacology revealed that CYTA could regulate oxidative stress, apoptosis, and calcium signaling. Cellular experiments demonstrated that CYTA decreased levels of CK, LDH, and MDA, as well as ROS production and Ca2+ concentration. Additionally, CYTA improved apoptosis and increased the activities of SOD, CAT, and GSH-Px, along with the levels of ATP and Ca2+-ATPase content and mitochondrial membrane potential. Moreover, CYTA inhibited ICa-L, cell contraction, and Ca2+ transient in cardiomyocytes. Results: These findings suggest that CYTA has a protective effect on MI by inhibiting oxidative stress, mitochondrial damage, apoptosis and Ca2+ overload. Discussion: The results prove that CYTA might be a potential natural compound in the field of MI treatment, and also provide a new scientific basis for the its utilization.

Myocardial infarction (MI) is a common type of ischemic heart disease that affects millions of people worldwide. In recent times, nanotechnology has become a very promising field with immense applications. The current exploration was conducted to synthesize the chitosan-sodium alginate-polyethylene glycol-Ally isothiocyanate nanocomposites (CSP-AIso-NCs) and evaluate their beneficial roles against the isoproterenol (ISO)-induced MI in rats. The CSP-AIso-NCs were prepared and characterized by several characterization techniques. The MI was initiated in the rats by the administration of 85 mg/kg of ISO for 2 days and treated with 10 and 20 mg/kg of CSP-AIso-NCs for 1 month. The changes in heart weight and bodyweight were measured. The cardiac function markers were assessed with echocardiography. The lipid profiles, Na+, K+, and Ca2+ ions, cardiac biomarkers, antioxidant parameters, and inflammatory cytokines were assessed using corresponding assay kits. The histopathological study was done on the heart tissues. The UV spectral analysis revealed the maximum peak at 208 nm, which confirms the formation of CSP-AIso-NCs. The FT-IR analysis revealed the occurrence of different functional groups, and the crystallinity of the CSP-AIso-NCs was proved by the XRD analysis. DLS analysis indicated the size of the CSP-AIso-NCs at 146.50 nm. The CSP-AIso-NCs treatment increased the bodyweight and decreased the HW/BW ratio in the MI rats. The status of lipids was reduced, and HDL was elevated in the CSP-AIso-NCs administered to MI rats. CSP-AIso-NCs decreased the LVEDs, LVEDd, and NT-proBNP and increased the LVEF level. The oxidative stress markers were decreased, and the antioxidants were increased by the CSP-AIso-NCs treatment in the MI rats. The Na+ and Ca+ ions were reduced, and the K+ ions were increased by the CSP-AIso-NCs. The interleukin-1β and tumor necrosis factor-α were also depleted, and Nrf-2 was improved in the CSP-AIso-NCs administered to MI rats. The histological study revealed the ameliorative effects of CSP-AIso-NCs. Overall, our outcomes revealed that the CSP-AIso-NCs are effective against the ISO-induced MI rats. Hence, it could be a hopeful therapeutic nanomedicine for MI treatment.

Cardiosphere-derived cells (CDCs) are currently being evaluated in clinical trials as a potential therapeutic tool for regenerative medicine. The effectiveness of transplanted CDCs is largely attributed to their ability to release beneficial soluble factors to enhance therapeutic effects. An emerging area of research is the pretreatment of stem cells, including CDCs, with various cytokines to improve their therapeutic properties. This strategy aims to enhance their survival, proliferation, differentiation, and paracrine activities after transplantation. In our study, we investigated the differential effects of various cytokines and TLR ligands on the secretory phenotype of human CDCs. Using a magnetic bead-based immunoassay, we analyzed the CDCs-conditioned media for 41 cytokines and growth factors and detected the presence of 21 cytokines. We found that CDC incubation with lipopolysaccharide, a TLR4 ligand, and the cytokine combination of TNF/IFN significantly increased the secretion of most of the cytokines detected. Specifically, we observed an increased secretion and gene expression of IP10, MCP3, IL8, and VEGFA. In contrast, the TLR3 ligand polyinosinic-polycytidylic acid and TGF-beta had minimal effects on CDC cytokine secretion. Additionally, TNF/IFN, but not LPS, enhanced ICAM1 expression. Our findings offer new insights into the role of cytokines in potentially modulating the biology and regenerative potential of CDCs.

Deltamethrin is one of the most effective pyrethroid compounds, widely employed in veterinary medicine, public health, and farming. Deltamethrin-triggered oxidative stress largely causes serious harm to an organism. Acute toxicity of this compound was extensively investigated, while less information is available on its oral sub-acute effects. This study assessed, in the male Albino rats, the effects of oral gavage of either 0.874 mg/kg (0.01 LD50) or 8.740 mg/kg (0.10 LD50) of deltamethrin for successive 14 days to investigate its effects on biomarkers and to detect the tissue injury in rats following subacute deltamethrin treatment. It was found that levels of glutathione peroxidase, superoxide dismutase, and catalase in the brain, kidney, and liver, alkaline phosphatase (ALP), and uric acid in serum, hematocrit, mean corpuscular volume (MCV), white blood cells (WBC)s, eosinophils, and basophils were significantly reduced compared with untreated rats. However, when rats were treated with deltamethrin for successive 14 days, alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities in serum and the levels of thiobarbituric acid reactive substances (TBARs) in brain, kidney, and liver, red blood cell distribution width (RDW-CV), total protein, monocytes, and basophils and the ratios of neutrophils to lymphocytes, an aggregated marker of systemic inflammation and systemic immune inflammation indexes, significantly increased compared with the control group. Histologic lesions were observed in the liver, kidney, brain, testis, and epidemies in rats exposed to subacute deltamethrin for 14 days, and most tissues of rats treated with 0.10 LD50 of deltamethrin were more affected than those treated with 0.01 LD50. These findings strongly suggest that subacute exposure to deltamethrin caused significant systemic toxicity through oxidative stress resulting in biochemical and histological changes in the studied tissues. These findings highlight the potential harmful effects of deltamethrin and emphasize the importance of understanding the subacute effects of this compound, particularly in the context of veterinary medicine, public health, and farming.

The objective of our study was to evaluate the concentrations of pro-inflammatory biomarkers in patients with acute myocardial infarction with non-obstructive coronary arteries (MINOCA) compared to patients with acute myocardial infarction with obstructive coronary arteries (MI-CAD) in the early post-infarction period and after 1 year and to perform a comparative analysis of the relationship between laboratory biomarkers and atherosclerosis progression in patients with MINOCA and MI-CAD.

Samples of peripheral venous blood were collected upon admission and on days 2, 4, and 7 of hospitalization and after 1 year. An extended multiplex analysis was performed in blood serum. Multidetector-computed tomography coronary angiography was performed on day 7 and 1 year after acute myocardial infarction to assess the progression of atherosclerosis.

The level of high-sensitive C-reactive protein (hsCRP) was elevated upon admission in MINOCA patients compared to MI-CAD patients (p = 0.05), but it was comparable in two groups at other time points and did not exceed the reference range after 1 year. Despite comparable levels of cytokines CXCL-6, LIGHT, CCL-8, and endocan-1 in patients in both groups, MINOCA patients had a greater increase in pro-inflammatory cytokines PlGF, oncostatin M, IL-20, and CCL-15 sVCAM-1 in the early post-infarction period and in CCL-21, sVCAM-1, oncostatin M, and PlGF after 1 year. We observed significant differences in the dynamics of the following biomarkers between patients with MI-CAD and MINOCA: the dynamics of concentrations of CCL21 (p = 0.002), LIGHT (p = 0.03), and endocan-1 (p = 0.03) after 1 year compared to day 1 in MI-CAD and MINOCA patients was opposite, while the dynamics of CXCL6 (p = 0.04) and endocan-1 (p = 0.02) differed between groups when evaluated after 1 year compared to day 7 of the early post-infarction period. In the MINOCA group, factors associated with atherosclerosis progression were concentrations of sVCAM-1 and CCL-21, while in the MI-CAD group, concentrations of CCL-8 and CXCL6 were the main determinants of atherosclerosis progression.

This small study showed that MINOCA and MI-CAD patients exhibited differences in a pro-inflammatory biomarker profile in the early post-infarction period and after 1-year follow-up, which implies distinct inflammatory pathways involved in atherogenesis during MINOCA. The key factors that were associated with atherosclerosis progression in MINOCA patients are sVCAM-1 and CCL-21, which may suggest a complex genesis of atherosclerosis progression due to structurally altered plaques and changes in the microcirculatory bed. In MI-CAD patients, CCL-8 and CXCL-6 were the key biomarkers associated with atherosclerosis progression. Further large-scale studies are required to confirm our data.

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematologic malignancies characterized by an abnormal proliferation of cells of the myeloid lineage. Affected individuals are at increased risk for cardiovascular and thrombotic events. Myocardial infarction (MI) may be one of the earliest clinical manifestations of MPNs or may be a thrombotic complication that develops during the natural course of the disease. In the present review, we examine the epidemiology, pathogenesis, clinical presentation, and management of MI in MPNs based on the available literature. Moreover, we review potential biomarkers that could mediate the MI-MPNs crosstalk, from classical biochemical tests, e.g., lactate dehydrogenase, creatine kinase and troponins, to pro-inflammatory cytokines, oxidative stress markers, and clonal hematopoiesis.

HIV-associated neurocognitive disorders (HANDs) continue to impact patients despite antiretroviral therapy. A combination of antiretroviral therapies can diminish the HIV viral load to near undetectable levels, but fails to preserve neurocognitive integrity. The cytokine leukemia inhibitory factor (LIF) has shown neuroprotective properties that could mitigate neurodegeneration in HANDs. The LIF promotes neurogenesis, neural cell differentiation, and survival. Combination antiretroviral therapy reduces severe forms of HANDs, but neurocognitive impairment persists; additionally, some antiretrovirals have additional adverse neurotoxic effects. The LIF counteracts neurotoxic viral proteins and limits neural cell damage in models of neuroinflammation. Adding the LIF as an adjuvant therapy to enhance neuroprotection merits further research for managing HANDs. The successful implementation of the LIF to current therapies would contribute to achieving a better quality of life for the affected population.