Search Results (84)

Atherosclerosis, a chronic inflammatory disease, remains a leading cause of cardiovascular mortality worldwide. Despite standard treatments like statins and percutaneous coronary intervention (PCI), significant residual risk and therapeutic limitations underscore the need for innovative strategies. This review summarizes recent advances in nanoparticle-based therapies for atherosclerosis, focusing on key developments from the last five years. We discuss various nanoplatforms designed to selectively target key cellular players in plaque pathogenesis, including macrophages, endothelial cells, and vascular smooth muscle cells (VSMCs), to inhibit inflammation, modulate cellular phenotypes, and stabilize plaques. A significant focus is placed on the emerging field of biomimetic nanoparticles, where therapeutic cores are camouflaged with cell membranes derived from macrophages, platelets, neutrophils, or erythrocytes. This approach leverages the natural biological functions of the source cells to achieve enhanced immune evasion, prolonged circulation, and precise targeting of atherosclerotic lesions. Furthermore, the review covers nanoparticles engineered for specific functional interventions, such as lowering LDL levels and exerting direct anti-inflammatory and anti-oxidative effects. Finally, we address the critical challenges hindering clinical translation, including nanotoxicity, biodistribution, and manufacturing scalability. In conclusion, nanotechnology offers a versatile and powerful platform for atherosclerosis therapy, with targeted and biomimetic strategies holding immense promise to revolutionize future cardiovascular medicine. Full article

Reactive nitrogen species (RNS), particularly peroxynitrite (ONOO⁻), play a central role in post-translational modifications (PTMs) of proteins, including fibrinogen, a key component of the coagulation cascade. This review explores the structural and functional consequences of fibrinogen nitration, with a focus on its impact on clot formation, morphology, mechanical stability, and fibrinolysis. Nitration, primarily targeting tyrosine residues within functional domains of the Aα, Bβ, and γ chains, induces conformational changes, dityrosine crosslinking, and aggregation into high molecular weight species. These modifications result in altered fibrin polymerization, the formation of porous and disorganized clot networks, reduced mechanical resilience, and variable susceptibility to fibrinolysis. Moreover, nitrated fibrinogen may affect interactions with platelets and endothelial cells, although current evidence remains limited. Emerging clinical studies support its role as both a prothrombotic mediator and a potential biomarker of oxidative stress in cardiovascular and inflammatory diseases. Finally, we explore both pharmacological interventions, such as NOX inhibitors, and natural antioxidant strategies at counteracting fibrinogen nitration. Overall, fibrinogen nitration emerges as a critical molecular event linking oxidative stress to thrombotic risk. Full article

Atherosclerotic cardiovascular disease (ASCVD) remains the leading global cause of morbidity and mortality, even in the era of aggressive low-density lipoprotein cholesterol (LDL-C) lowering. This persistent residual risk has prompted a reevaluation of atherogenic lipid markers, with non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (Apo B) emerging as superior indicators of the total atherogenic particle burden. Unlike LDL-C, non-HDL-C includes cholesterol from all atherogenic lipoproteins, while Apo B reflects the total number of atherogenic particles regardless of cholesterol content. Their clinical relevance is underscored in populations with diabetes, obesity, and hypertriglyceridemia, where LDL-C may not adequately reflect cardiovascular risk. This review explores the biological, clinical, and genetic foundations of non-HDL-C and Apo B as critical tools for risk stratification and therapeutic targeting. It highlights discordance analysis, inflammatory mechanisms in atherogenesis, the influence of metabolic syndromes, and their utility in specific populations, including those with chronic kidney disease and children with familial hypercholesterolemia. Additionally, the role of lipoprotein (a), glycation in diabetes, and hypertriglyceridemia are examined as contributors to residual risk. Clinical trials and genetic studies support Apo B and non-HDL-C as more robust predictors of cardiovascular events than LDL-C. Current guidelines increasingly endorse these markers as secondary or even preferred targets in complex lipid disorders. The incorporation of Apo B and non-HDL-C into routine clinical practice, especially for patients with residual risk, represents a paradigm shift toward personalized cardiovascular prevention. The review concludes with recommendations for guideline integration, emerging therapies, and future directions in biomarker-driven cardiovascular risk management. Full article

Background/Objectives: Patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) exhibit increased cardiovascular risk, partly attributed to persistent systemic inflammation. Janus kinase inhibitors (JAKi) effectively reduce inflammation, but their impact on cardiovascular risk remains unclear. This pilot study aimed to evaluate the effect of JAKi therapy on systemic inflammation and lipid markers, correlate traditional cardiovascular risk factors with biological parameters, and quantify subclinical atherosclerosis progression. Methods: We conducted a prospective, single-center study including 48 patients receiving JAKi. Clinical, inflammatory, lipid, and vascular parameters were assessed at baseline (T0) and after 12 months (T1). Primary endpoints included changes in carotid intima-media thickness (cIMT), ankle-brachial index (ABI), and carotid plaque presence. Results: Mean cIMT significantly decreased from 0.29 mm to 0.125 mm (p = 0.019), while ABI improved modestly, but not significantly (0.125 to 0.04, p = 0.103). Carotid plaque prevalence increased slightly from 39.6% to 47.9%, p = 0.159. C-reactive protein (CRP) levels declined significantly, while interleukin (IL)-1β levels increased. Lipoprotein(a) [Lp(a)] levels decreased significantly (mean reduction −7.96 mmol/L, p = 0.001). Multivariate regression identified Lp(a) as an independent predictor of carotid plaque at both T0 (p = 0.011) and T1 (p = 0.005). Baseline ABI was a significant predictor of acute cardiovascular events [hazard ratio (HR): 4.614, 95% CI: 1.034–20.596, p = 0.045]. Conclusions: JAKi therapy significantly reduced systemic inflammation and cIMT in patients with autoimmune rheumatic diseases, suggesting a potential benefit in attenuating early vascular changes. However, residual cardiovascular risk remains in patients with low ABI and elevated Lp(a), warranting close monitoring. Full article

The marine environment, covering over 70% of the Earth’s surface, serves as a reservoir of bioactive molecules, including peptides and proteins. Due to the unique and often extreme marine conditions, these molecules exhibit distinctive structural features and diverse functional properties, making them promising candidates for therapeutic applications. Marine-derived bioactive peptides, typically consisting of 3 to 40 amino acid residues—though most commonly, 2 to 20—are obtained from parent proteins through chemical or enzymatic hydrolysis, microbial fermentation, or gastrointestinal digestion. Like peptides, protein hydrolysates from collagen, a dominant protein of such materials, play an important role. Peptide bioactivities include antioxidant, antihypertensive, antidiabetic, antimicrobial, anti-inflammatory, anticoagulant, and anti-cancer effects as well as immunoregulatory and wound-healing activities. These peptides exert their effects through mechanisms such as enzyme inhibition, receptor modulation, and free radical scavenging, among others. Fish, algae, mollusks, crustaceans, microbes, invertebrates, and marine by-products such as skin, bones, and viscera are some of the key marine sources of bioactive proteins and peptides. The advancements in the extraction and purification processes, e.g., enzymatic hydrolysis, ultrafiltration, ion-exchange chromatography, high-performance liquid chromatography (HPLC), and molecular docking, facilitate easy identification and purification of such bioactive peptides in greater purity and activity. Despite their colossal potential, their production, scale-up, stability, and bioavailability are yet to be enhanced for industrial applications. Additional work needs to be carried out for optimal extraction processes, to unravel the mechanisms of action, and to discover novel marine sources. This review emphasizes the enormous scope of marine-derived peptides and proteins in the pharmaceutical, nutraceutical, cosmeceutical, and functional food industries, emphasizing their role in health promotion and risk reduction of chronic diseases. Full article

Animal-derived foods constitute a crucial source of nutrients for humans. The judicious application of steroid hormones in the breeding process can serve multiple purposes, including growth promotion, weight gain, and anti-inflammatory effects, among others. However, excessive misuse poses a considerable risk to both food safety and consumer health. Currently, the primary means of detecting steroid hormones involve liquid chromatography, gas chromatography, and their combination with mass spectrometry. These methods necessitate advanced instrumentation, intricate pretreatment procedures, and the expertise of specialized laboratories and technicians. In recent years, the swift evolution of analytical science, technology, and instrumentation has given rise to various rapid detection techniques for steroid hormone residues, providing a robust technical foundation for ensuring food safety. This review commences by delineating the roles of steroid hormones, the associated residue hazards, and the pertinent residue restriction standards. Subsequently, it delves deeply into the analysis of the most recent rapid detection techniques for steroid hormones, ultimately culminating in an assessment of the challenges currently confronting the field, along with an exploration of potential future advancements. We sincerely hope that this review will inspire and provide valuable insights to the pertinent researchers. Full article

Background/Objectives: Synthetic polyethylene glycol (PEG)-based hydrogel sealants, such as Adherus, are commonly used in spinal surgeries to achieve watertight dural closure and prevent cerebrospinal fluid (CSF) leaks. This case report describes an unusual instance of suspected hydrogel sealant migration resulting in an intradural collection at a spinal level remote from the original surgery. Methods: A 57-year-old female with a history of osteoarthritis and prediabetes underwent a minimally invasive L5-S1 laminectomy for the removal of an epidural abscess causing cauda equina and S1 nerve root compression. During the procedure, a dural puncture occurred, which was repaired using Duragen (collagen matrix) and Adherus (synthetic PEG hydrogel sealant). Postoperatively, the patient developed urinary retention and new bilateral posterior leg pain. An MRI on postoperative day four revealed a new peripherally enhancing dorsal intradural collection at the L2 level, causing significant thecal sac narrowing and compression of the cauda equina nerve roots, suggestive of migration of the hydrogel sealant used during surgery. Conservative management was adopted. Results: The patients symptoms gradually resolved. Follow-up imaging at five months showed resolution of the intradural collection, with residual intradural inflammatory changes and arachnoiditis. Conclusions: While PEG-based hydrogel sealants like Adherus are effective in preventing CSF leaks, they can, in rare instances, migrate and cause remote intradural collections with neurological symptoms. Surgeons should exercise meticulous application techniques, thoroughly document the use of sealants, and maintain vigilant postoperative monitoring to mitigate these risks. Full article

Introduction: The variants rs10517086 and rs1534422 are predictive of type 1 diabetes mellitus (T1DM) development and poor residual β cell function within the first year of diagnosis. However, the mechanism by which risk is conferred is unknown. We explored the impact of both variants on β cell function in vitro and assessed their relationship with C-peptide in people with T1DM and type 2 diabetes mellitus (T2DM). Methods: Using CRISPR/Cas9, the variants were introduced into a β cell line (BRIN-BD11) and a T cell line (Jurkat cells) from which the conditioned media was applied to otherwise healthy β cells to model the inflammatory environment associated with these variants. Results: Both variants significantly reduced glucose-stimulated insulin secretion, increased production of pro-inflammatory cytokines and reduced expression of several β cell markers and transcription factors (KCNJ11, KCNQ1, SCL2A2, GCK, NKX6.1, Pdx1 NGN3). However, HNF1A was significantly upregulated in the presence of both variants. We subsequently silenced HNF1A in variant expressing BRIN-BD11 cells using siRNA and found that gene expression profiles were normalised. Induction of each variant significantly increased expression of the lncRNAs they encode, which was normalised upon HNF1A silencing. Analysis of the DARE (Diabetes Alliance for Research in England) study revealed an association of rs10517086_A genotype with C-peptide in 153 individuals with T1DM, but not in 417 people with T2DM. Conclusions: These data suggest that rs1534422 and rs10517086 exert multiple insults on the β cell through excessive upregulation of HNF1A and induction of pro-inflammatory cytokines, and highlight their utility as prognostic markers of β cell function. Full article

Atherothrombosis, the primary driver of acute cardiovascular (CV) events, is characterized by the activation of three key pathophysiological pathways: platelets, coagulation, and inflammation. Dual antiplatelet therapy (DAPT) is the current standard of care for patients with acute coronary syndrome, providing significant reductions in cardiovascular (CV) events, albeit with an associated increased risk of bleeding. However, the high residual risk of recurrent events among these patients highlights the need for alternative strategies to treat and prevent atherothrombosis. To this extent, several approaches aimed at targeting atherothrombosis have been proposed. Among these, a strategy of dual-pathway inhibition simultaneously targeting platelets, using single or DAPT, and coagulation, using a low-dose anticoagulant such as rivaroxaban 2.5 mg twice daily, has shown to reduce CV events but at the expense of increased bleeding. Targeting inflammatory pathways has the potential to be a highly effective strategy to tackle atherothrombosis without increasing bleeding risk. Several anti-inflammatory agents have been tested in patients with coronary artery disease, but to date only colchicine is approved for secondary prevention on top of standard care, including antiplatelet therapy. However, many aspects of colchicine’s mechanism of action, including its antiplatelet effects and how it synergizes with antiplatelet therapy, remain unclear. In this review, we summarize the available clinical and pre-clinical evidence on the antiplatelet effects of colchicine and its synergistic interactions with antiplatelet therapy, highlighting their potential role in addressing atherothrombosis. Full article

Dual inhibition of cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) is a recognized strategy for enhanced anti-inflammatory effects in small molecules, offering potential therapeutic benefits for individuals at risk of dementia, particularly those with neurodegenerative diseases, common cancers, and diabetes type. Alzheimer’s disease (AD) is the most common cause of dementia, and the inhibition of acetylcholinesterase (AChE) is a key approach in treating AD. Meanwhile, Caspase-3 catalyzes early events in apoptosis, contributing to neurodegeneration and subsequently AD. Structure-based virtual screening of US-FDA-approved molecules from the ZINC15 database identified clozapine (CLOZ) as the dual inhibitor of COX-2 and AChE, with significant binding affinity. Further molecular docking of CLOZ in the active site of LOX and Caspase-3 also showed significant binding potential. Further, the results from molecular docking were validated using molecular dynamics simulation (MDS) studies, confirming the results from molecular docking. The results from MDS showed good binding potential and interactions with key residues. The CLOZ was further assessed using lipopolysaccharide (LPS)-challenged rats treated for thirty days at doses of 5 and 10 mg/kg, p.o. The results demonstrated modulation of COX-2, 5-LOX, AChE, Caspase-3, and MDA in LPS-induced brains. Additionally, the expression level of IL-10 was also measured. Our results showed a significant decrease in the levels of COX-2, 5-LOX, AChE, Caspase-3, and MDA. Our results also showed a significant decrement in the pro-inflammatory markers NF-κB, TNF-α, and IL-6 and an improvement in the levels of anti-inflammatory markers IL-10 and TGF-β1. Overall, the findings indicate that CLOZ has potential for neuroprotective effects against LPS-treated rats and can be explored. Full article

Selenium (Se) is an essential trace element that is crucial for human health. As a key component of various enzymes and proteins, selenium primarily exerts its biological functions in the form of selenoproteins within the body. Currently, over 30 types of selenoproteins have been identified, with more than 20 of them containing selenocysteine residues. Among these, glutathione peroxidases (GPXs), thioredoxin reductases (TrxRs), and iodothyronine deiodinases (DIOs) have been widely studied. Selenium boasts numerous biological functions, including antioxidant properties, immune system enhancement, thyroid function regulation, anti-cancer effects, cardiovascular protection, reproductive capability improvement, and anti-inflammatory activity. Despite its critical importance to human health, the range between selenium’s nutritional and toxic doses is very narrow. Insufficient daily selenium intake can lead to selenium deficiency, while excessive intake carries the risk of selenium toxicity. Therefore, selenium intake must be controlled within a relatively precise range. This article reviews the distribution and intake of selenium, as well as its absorption and metabolism mechanisms in the human body. It also explores the multiple biological functions and mechanisms of selenium in maintaining human health. The aim is to provide new insights and evidence for further elucidating the role of selenium and selenoproteins in health maintenance, as well as for future nutritional guidelines and public health policies. Full article

Cancer recurrence and metastasis remain critical challenges following surgical resection, influenced by complex perioperative mechanisms. This review explores how surgical stress triggers systemic changes, such as neuroendocrine responses, immune suppression, and inflammation, which promote the dissemination of residual cancer cells and circulating tumor cells. Key mechanisms, such as epithelial–mesenchymal transition and angiogenesis, further enhance metastasis, while hypoxia-inducible factors and inflammatory responses create a microenvironment conducive to tumor progression. Anesthetic agents and techniques modulate these mechanisms in distinct ways. Inhaled anesthetics, such as sevoflurane, may suppress immune function by increasing catecholamines and cytokines, thereby promoting cancer progression. In contrast, propofol-based total intravenous anesthesia mitigates stress responses and preserves natural killer cell activity, supporting immune function. Opioids suppress immune surveillance and promote angiogenesis through the activation of the mu-opioid receptor. Opioid-sparing strategies using NSAIDs show potential in preserving immune function and reducing recurrence risk. Regional anesthesia offers benefits by reducing systemic stress and immune suppression, though the clinical outcomes remain inconsistent. Additionally, dexmedetomidine and ketamine exhibit dual effects, both enhancing and inhibiting tumor progression depending on the dosage and context. This review emphasizes the importance of individualized anesthetic strategies to optimize long-term cancer outcomes. While retrospective studies suggest potential benefits of propofol-based total intravenous anesthesia and regional anesthesia, further large-scale trials are essential to establish the definitive role of anesthetic management in cancer recurrence and survival. Full article

Omega-3 fatty acids reduce triglycerides and have several positive effects on different organs and systems. They are also found in the plasma membrane in variable amounts in relation to genetics and diet. However, it is still unclear whether omega-3 supplementation can reduce the occurrence of major cardiovascular events (MACEs). Two trials, REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), with highly purified EPA, and STRENGTH (Effect of High-Dose Omega-3 Fatty Acids vs. Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk), with a combination of EPA and DHA, have produced different outcomes, triggering a scientific debate on possible explanations for the discrepancies. Furthermore, doubts have arisen as to the anti-inflammatory and anti-aggregating activity of these compounds. Recent studies have, however, highlighted interesting effects of EPA and DHA on erythrocyte membrane fluidity (EMF). EMF is governed by a complex and dynamic biochemical framework, with fatty acids playing a central role. Furthermore, it can be easily measured in erythrocytes from a blood sample using fluorescent probes. Recent research has also shown that EMF could act as a possible cardiovascular risk factor biomarker. This review aims to synthetize the latest evidence on erythrocyte membrane fluidity, exploring its potential role as a biomarker of residual cardiovascular risk and discussing its clinical relevance. Further, we aim to dissect the possible biological mechanisms that link omega-3 modifiable membrane fluidity to cardiovascular health. Full article

Anthocyanins are significant secondary metabolites that are essential for plant growth and development, possessing properties such as antioxidant, anti-inflammatory, and anti-cancer activities and cardiovascular protection. They offer significant potential for applications in food, medicine, and cosmetics. However, since anthocyanins are mainly obtained through plant extraction and chemical synthesis, they encounter various challenges, including resource depletion, ecological harm, environmental pollution, and the risk of toxic residuals. To address these issues, this study proposes a plant cell factory approach as a novel alternative solution for anthocyanin acquisition. In this study, the VdCHS2 gene was successfully transformed into spine grape cells, obtaining a high-yield anthocyanin cell line designated as OE1. Investigations of the light spectrum demonstrated that white light promoted spine grape cell growth, while short-wavelength blue light significantly boosted anthocyanin production. Targeted metabolomics analysis revealed that the total anthocyanin content in the OE1 cell line reached 11 mg/g, representing a 60% increase compared to the WT. A total of 54 differentially accumulated metabolites were identified, among which 44 were upregulated. Overexpression of the CHS gene enhanced the expression of downstream genes involved in anthocyanin biosynthesis, resulting in the differential expression of CHI, F3Hb, F3′5′H, DFR4, and LDOX. This led to the differential accumulation of anthocyanin monomers, predominantly consisting of 3-O-glucosides and 3-O-galactosides, thereby causing alterations in anthocyanin levels and composition. Furthermore, the OE1 cell line increased the activity of various antioxidant enzymes, improved the clearance of reactive oxygen species, and reduced the levels of hydrogen peroxide (H₂O₂) and malondialdehyde (MDA). The subsequent cultivation of the transformed OE1 cell line, in conjunction with cell suspension culture, established a plant cell factory for anthocyanin production, significantly increasing anthocyanin yield while shortening the culture duration. This study elucidates the molecular mechanisms through which the VdCHS2 gene influenced anthocyanin accumulation and compositional variations. Additionally, it established a model for a small-scale anthocyanin plant cell factory, thereby providing a theoretical and practical foundation for the targeted synthesis of anthocyanin components and the development and utilization of plant natural products. Full article

Lung cancer remains a leading cause of cancer-related mortality worldwide. Although surgical treatment is a primary approach, residual cancer cells and surgery-induced pathophysiological changes may promote cancer recurrence and metastasis. Anesthetic agents and techniques have recently been shown to potentially impact these processes by modulating surgical stress responses, immune function, inflammatory pathways, and the tumor microenvironment. Anesthetics can influence immune-modulating cytokines, induce pro-inflammatory factors such as HIF-1α, and alter natural-killer cell activity, affecting cancer cell survival and spread. Preclinical studies suggest volatile anesthetics may promote tumor progression by triggering pro-inflammatory signaling, while propofol shows potential antitumor properties through immune-preserving effects and reductions in IL-6 and other inflammatory markers. Additionally, opioids are known to suppress immune responses and stimulate pathways that may support cancer cell proliferation, whereas regional anesthesia may reduce these risks by decreasing the need for systemic opioids and volatile agents. Despite these findings, clinical data remain inconclusive, with studies showing mixed outcomes across patient populations. Current clinical trials, including comparisons of volatile agents with propofol-based total intravenous anesthesia, aim to provide clarity but highlight the need for further investigation. Large-scale, well-designed studies are essential to validate the true impact of anesthetic choice on cancer recurrence and to optimize perioperative strategies that support long-term oncologic outcomes for lung cancer patients. Full article