Metabolic disorders of cardiomyocytes play an important role in the progression of various cardiovascular diseases. Metabolic reprogramming can provide ATP to cardiomyocytes and protect them during diseases, but this transformation also leads to adverse consequences such as oxidative stress, mitochondrial dysfunction, and eventually aggravates myocardial injury. Moreover, abnormal accumulation of metabolites induced by metabolic reprogramming of cardiomyocytes alters the cardiac microenvironment and affects the metabolism of immune cells. Immunometabolism, as a research hotspot, is involved in regulating the phenotype and function of immune cells. After myocardial injury, both cardiac resident immune cells and heart-infiltrating immune cells significantly contribute to the inflammation, repair and remodeling of the heart. In addition, metabolites generated by the metabolic reprogramming of immune cells can further affect the microenvironment, thereby affecting the function of cardiomyocytes and other immune cells. Therefore, metabolic reprogramming and abnormal metabolite levels may serve as a bridge between cardiomyocytes and immune cells, leading to the development of cardiovascular diseases. Herein, we summarize the metabolic relationship between cardiomyocytes and immune cells in cardiovascular diseases, and the effect on cardiac injury, which could be therapeutic strategy for cardiovascular diseases, especially in drug research.

Depression is a complicated neuropsychiatric disorder with multifactorial etiology, involving alterations in behavior, neuroinflammatory processes, and oxidative homeostasis. Chronic stress disrupts synaptic plasticity and promotes neuroinflammation and redox imbalance, with pronounced effects in the medial prefrontal cortex (mPFC). Xanthohumol (XN), a prenylated flavonoid, has demonstrated neuroprotective properties; however, its therapeutic potential in the context of stress-induced depression has not been fully exploited.

This study aims to examine whether XN alleviates depressive-like behaviors in a chronic unpredictable mild stress (CUMS) mouse model, as well as to delve into the underlying mechanisms involving neuroinflammation, oxidative stress, synaptic function, and the Sirt1/NF-κB/NLRP3 signaling pathway.

Male C57BL/6J mice were subjected to a 3-week CUMS protocol and administered XN at a dose of 20 mg/kg via intragastric gavage. Behavioral evaluations included the sucrose preference test, tail suspension test, and forced swim test to assess anhedonia and behavioral despair. mPFC tissues were collected for analysis of neuroinflammatory cytokines, Nissl staining, immunofluorescence, oxidative stress biomarkers, and synaptic protein expression. In addition, protein levels of Sirt1, phosphorylated NF-κB (phospho-NF-κB), total NF-κB, and NLRP3 in the mPFC were quantified via western blotting analysis.

XN treatment significantly ameliorated depressive-like behaviors and enhanced synaptic protein expression within the mPFC. XN markedly diminished the pro-inflammatory cytokines expression and attenuated oxidative stress via the activation of the Nrf2/HO-1 signaling pathway, thereby boosting the brain's antioxidant capacity. Additionally, XN upregulated the expression of Sirt1 and suppressed the NF-κB/NLRP3 inflammasome pathway activation.

XN exerts antidepressant-like impact through the Sirt1/NF-κB/NLRP3 and Nrf2/HO-1 pathways, highlighting XN as a potentially effective therapeutic alternative for stress-induced depression.

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of plaque within the arteries. Despite advances in therapeutic strategies including anti-inflammatory, antioxidant, and lipid metabolism modulation treatments over the past two decades, the treatment of atherosclerosis remains challenging, as arterial damage is the result of interconnected pathological factors. Therefore, current monotherapies often fail to address the complex nature of this disease, leading to insufficient therapeutic outcomes. This review addressed this paucity of effective treatment options by comprehensively exploring the potential for combination therapies and advanced drug co-delivery systems for the treatment of atherosclerosis. We investigated the pathological features of and risk factors for atherosclerosis, underscoring the importance of drug combination therapies for the treatment of atherosclerotic diseases. We discuss herein mathematical models for quantifying the efficacy of the combination therapies and provide a systematic summary of drug combinations for the treatment of atherosclerosis. We also provide a detailed review of the latest advances in nanoparticle-based drug co-delivery systems for the treatment of atherosclerosis, focusing on the design of carriers with high biocompatibility and efficacy. By exploring the possibilities and challenges inherent to this approach, we aim to highlight cutting-edge technologies that can foster the development of innovative strategies, optimize drug co-administration, improve treatment outcomes, and reduce the burden of atherosclerosis-related morbidity and mortality on the healthcare system.

Mitochondria regulate macrophage function, affecting cardiovascular diseases like atherosclerosis and heart failure. Their dynamics interact with macrophage cell death mechanisms, including apoptosis and necroptosis.

This review explores how mitochondrial dynamics and metabolism influence macrophage inflammation and cell death in CVDs, highlighting therapeutic targets for enhancing macrophage resilience and reducing CVD pathology, while examining molecular pathways and pharmacological agents involved.

This is a narrative review that integrates findings from various studies on mitochondrial dynamics and metabolism in macrophages, their interactions with the endoplasmic reticulum (ER) and Golgi apparatus, and their implications for CVDs. The review also considers the potential therapeutic effects of pharmacological agents on these pathways.

The review utilizes a comprehensive literature search to identify relevant studies on mitochondrial dynamics and metabolism in macrophages, their role in CVDs, and the effects of pharmacological agents on these pathways. The selected studies are analyzed and synthesized to provide insights into the complex relationships between mitochondria, the ER, and Golgi apparatus, and their implications for macrophage function and fate.

The review reveals that mitochondrial metabolism intertwines with cellular architecture and function, particularly through its intricate interactions with the ER and Golgi apparatus. Mitochondrial-associated membranes (MAMs) facilitate Ca2+ transfer from the ER to mitochondria, maintaining mitochondrial homeostasis during ER stress. The Golgi apparatus transports proteins crucial for inflammatory signaling, contributing to immune responses. Inflammation-induced metabolic reprogramming in macrophages, characterized by a shift from oxidative phosphorylation to glycolysis, underscores the multifaceted role of mitochondrial metabolism in regulating immune cell polarization and inflammatory outcomes. Notably, mitochondrial dysfunction, marked by heightened reactive oxygen species generation, fuels inflammatory cascades and promotes cell death, exacerbating CVD pathology. However, pharmacological agents such as Metformin, Nitazoxanide, and Galanin emerge as potential therapeutic modulators of these pathways, offering avenues for mitigating CVD progression.

This review highlights mitochondrial dynamics and metabolism in macrophage inflammation and cell death in CVDs, suggesting therapeutic targets to improve macrophage resilience and reduce pathology, with new pharmacological agents offering treatment opportunities.

Atherosclerosis (AS) is a chronic vascular disorder that is characterized by the thickening and narrowing of arteries due to the development of atherosclerotic plaques. The traditional risk factors involved in AS are obesity, type 2 diabetes (T2D), dyslipidemia, hypertension, and smoking. Furthermore, non-traditional risk factors for AS, such as inflammation, sleep disturbances, physical inactivity, air pollution, and alterations of gut microbiota, gained attention in relation to the pathogenesis of AS. Interestingly, the pathogenesis of AS, is complex and related to different abnormalities of cellular and sub-cellular signaling pathways. It has been illustrated that AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (MTOR) pathways are involved in AS pathogenesis. Mounting evidence indicated that AMPK plays a critical role in attenuating the development of AS by activating autophagy, which is impaired during atherogenesis. AMPK has a vasculoprotective effect by reducing lipid accumulation, inflammatory cell proliferation, and the release of pro-inflammatory cytokines, as well as decreasing inflammatory cell adhesion to the vascular endothelium. AMPK activation by metformin inhibits the migration of vascular smooth muscle cells (VSMCs) and AS development. However, the MTOR pathway contributes to AS by inhibiting autophagy, highlighting autophagy as a crucial link between the AMPK and MTOR pathways in AS pathogenesis. The MTOR is a key inducer of endothelial dysfunction and is involved in the development of AS. Therefore, both the AMPK and MTOR pathways play a crucial role in the pathogenesis of AS. However, the exact role of AMPK and MTOR pathways in the pathogenesis of AS is not fully clarified. Therefore, this review aims to discuss the potential role of the AMPK/MTOR signaling pathway in AS, and how AMPK activators and MTOR inhibitors influence the development and progression of AS. In conclusion, AMPK activators and MTOR inhibitors have vasculoprotective effects against the development and progression of AS.

Dietary modification plays a crucial role in preventing cardiovascular diseases (CVDs), but evidence linking specific diets to stroke and acute myocardial infarction (AMI) is limited. This study investigates causal relationships between defined dietary exposures (e.g., fruit/vegetable intake, muesil consumption) and CVD outcomes, while evaluating the potential mediating role of high-density lipoprotein cholesterol (HDL-C). We employed two-sample Mendelian randomization (MR) using genetic data from genome-wide association studies (GWAS) in the UK Biobank and IEU database, validated with FinnGen data, to examine causal relationships between 83 dietary habits and CVD. Additionally, a meta-analysis was conducted using studies from PubMed and Web of Science to assess diet-stroke associations. Random-effects models were applied to estimate pooled relative risks (RR), with sensitivity analyses for robustness. MR identified eight significant diet-AMI and eighteen diet-stroke associations, but HDL-C did not mediate the diet-stroke relationship. The meta-analysis of 50 studies confirmed a link between specific diets and stroke risk. This study confirms associations between specific dietary factors and stroke/AMI, though HDL-C's role in AMI is unclear. These results reinforce the importance of targeted dietary modifications in primary prevention, and further research is needed to clarify underlying mechanisms.

Diabetic cardiomyopathy (DCM) is a global health concern. However, studies examining the effect of metformin on diabetes-induced cardiac myocyte aging are lacking. This study aimed to investigate the protective effect of metformin against DCM involving modulation of macrophage phenotypes, growth differentiation factor-15 (GDF-15), and the anti-aging protein Klotho. Diabetes was induced in male Wistar rats using streptozotocin. Diabetic and nondiabetic rats were treated with metformin (200 mg/kg/day) and saline (control). DCM, inflammation, adhesion molecules, immunometabolic, and GDF-15 biomarkers were assessed using immunoassays. Western blotting was used to analyze Klotho expression. Macrophage phenotypes, senescence-associated-galactosidase (SA-β-gal), and p16INK4a were examined using immunohistochemistry, whereas the heart sections were histologically examined. The untreated diabetic rats showed increased serum troponin I and creatine kinase-MB levels, reflecting cardiac damage, which was confirmed via morphological changes and senescence. Klotho expression was decreased, indicating cardiac aging. Treatment with metformin reduced the heart weight-body weight ratio and lowered cardiac injury, inflammation, and adhesion molecule biomarker levels. It also reversed the histopathological changes induced by diabetes. It shifted macrophage polarization toward the M2 phenotype, decreased p16INK4a and SA-β-gal expression, and enhanced Klotho and GDF-15 expression. These findings revealed that diabetes induces cardiac aging by increasing senescence markers and decreasing the expression of Klotho. Metformin treatment protects against DCM by modulating macrophage phenotypes, attenuating immunosenescence-related dysregulation, and enhancing GDF-15 and Klotho expressions. Thus, metformin has potential clinical implications in alleviating DCM.

Macrophages perform an essential role in the body's defense mechanisms and tissue homeostasis. These cells exhibit plasticity and are categorized into two phenotypes, including classically activated/M1 pro-inflammatory and alternatively activated/M2 anti-inflammatory phenotypes. Functional deviation in macrophage polarization occurs in different pathological conditions that need correction. In addition to antidiabetic impacts, metformin also possesses multiple biological activities, including immunomodulatory, anti-inflammatory, anti-tumorigenic, anti-aging, cardioprotective, hepatoprotective, and tissue-regenerative properties. Metformin can influence the polarization of macrophages toward M1 and M2 phenotypes. The ability of metformin to support M2 polarization and suppress M1 polarization could enhance its anti-inflammatory properties and potentiate its protective effects in conditions such as chronic inflammatory diseases, atherosclerosis, and obesity. However, in metformin-treated tumors, the proportion of M2 macrophages is decreased, while the frequency ratio of M1 macrophages is increased, indicating that metformin can modulate macrophage polarization from a pro-tumoral M2 state to an anti-tumoral M1 phenotype in malignancies. Metformin affects macrophage polarization through AMPK-dependent and independent pathways involving factors, such as NF-κB, mTOR, ATF, AKT/AS160, SIRT1, STAT3, HO-1, PGC-1α/PPAR-γ, and NLRP3 inflammasome. By modulating cellular metabolism and apoptosis, metformin can also influence macrophage polarization. This review provides comprehensive evidence regarding metformin's effects on macrophage polarization and the underlying mechanisms. The polarization-inducing capabilities of metformin may provide significant therapeutic applications in various inflammatory diseases and malignant tumors.

Atherosclerosis is a chronic inflammatory disease characterized by lipid streaks, which are produced by aggregates of lipid-rich foam cells. Foam cells intensify atherosclerosis by secreting a range of inflammatory mediators. Neutrophil extracellular traps produced by activated neutrophils, which are abundantly present in lipid-accumulating plaques. However, the relationship between neutrophil extracellular traps and foam cells inflammation is still unclear. Paeonol is well known for its anti-inflammatory effects in atherosclerosis. Nevertheless, the exact pharmacological mechanisms by which paeonol affects atherosclerosis are not fully understood which require further investigation. The purpose of this study is to investigate the effects of paeonol on the neutrophil extracellular traps' formation and foam cell inflammation caused by neutrophil extracellular traps, and to explore the potential mechanisms. A high-fat diet was administered to ApoE-/- mice for a period of 12 weeks to induce an atherosclerosis model. Our findings demonstrated that paeonol notably suppressed the advancement of atherosclerosis in ApoE-/- mice, curtailed the formation of neutrophil extracellular traps, and lowered inflammatory factor levels within the plaque. In vitro studies have shown that neutrophil extracellular traps could enhance the inflammation in foam cells. CitH3 played a role in the cellular communication between neutrophil extracellular traps and foam cells. Concurrently, NLRP3 acted as a key receptor in the inflammation mediated by this interaction. Paeonol is capable of regulating NE, thereby affecting the formation of neutrophil extracellular traps. Most notably, the foam cell inflammation caused by neutrophil extracellular traps was significantly mitigated by the inclusion of paeonol. Our findings suggested that paeonol inhibited foam cell inflammation which induced by neutrophil extracellular traps through the CitH3/NLRP3/caspase-1 signaling pathway, shedding new lights on its anti-atherosclerotic pharmacological mechanism.

Epigenetics of N6-methyladenine (m6A) modification may play a key role during the regulation of various diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). The m6A modification has been shown to be accomplished via the exploitation of several players such as methyltransferases, demethylases, and/or methylation-binding molecules. Significantly, the m6A methylation can regulate the key eukaryotic transcriptome by affecting the subcellular localization, splicing, export, stability, translation, and decay of those RNAs. An increasing amount of data has designated that the m6A modification of RNAs can also modulate the expression of autophagy-related genes, which could also control the autophagy in hepatocytes. Oxidative stress with reactive oxygen species (ROS) can induce m6A RNA methylation, which might be associated with the regulation of mitochondrial autophagy (mitophagy) and/or the development of MASLD. Therefore, both autophagy and the m6A modification could play important roles in regulating the pathogenesis of MASLD. Comprehending the relationship between m6A and mitophagy may be helpful for the development of future therapeutic strategies against MASLD. This review would advance the understanding of the regulatory mechanisms of m6A RNA modification, focusing on the impact of mitochondrial dysregulation and mitophagy in the liver with MASLD.

Hypertension represents a highly prevalent chronic condition and stands among the foremost contributors to premature mortality on a global scale. Its etiopathogenesis is intricate and multifaceted, being shaped by a diverse array of elements such as age, genetic predisposition, and activation of the neuroendocrine apparatus. Mounting evidence has shed light on the significant part that autoimmune responses play in hypertension and the ensuing damage to end organs. Virtually all varieties of immune cells, spanning both innate and adaptive immune compartments, exhibit a close correlation with the progression of hypertension. These immune cells infiltrate the kidney and vascular mesenchyme, subsequently discharging potent cytokines, reactive oxygen species, and metalloproteinases. This cascade of events can affect the functionality of local blood vessels and potentially precipitate adverse structural and functional alterations in crucial organs like the heart and kidney. In recent times, the management of end-organ damage in hypertension has emerged as a pivotal scientific focus. A multitude of researchers are actively engaged in probing efficacious intervention regimens, among which immunotherapy strategies hold considerable promise and anticipation as a prospective avenue.

The NLRP3 inflammasome plays a pivotal role in the innate immune response. Its activation involves a two-step mechanism that consists of priming and activation. The priming of the NLRP3 inflammasome is a vital initial phase necessary for its activation and subsequent involvement in the immune response, though its understanding varies across studies. Recent research has identified key proteins that influence the priming process, revealing a sophisticated regulatory network. This review provides a comprehensive review of the priming phase of NLRP3 inflammasome activation, with a particular focus on the underlying molecular mechanisms, including transcriptional regulation, orchestration of the phosphorylation status, deubiquitination and the relationships with the inflammation-associated diseases. Understanding the intricacies of NLRP3 inflammasome priming not only elucidates fundamental aspects of immune regulation, but also provides potential avenues for therapeutic intervention in inflammatory diseases.

Metformin has shown benefits in treating metabolic dysfunction-associated steatotic liver disease (MASLD), but its mechanisms remain unclear. This study investigates miR-200a-5p's role in the AMPK/SERCA2b pathway to reduce liver fat accumulation and ER stress in MASLD.

A PA cell model induced by palmitic and oleic acids (2:1) was used to assess lipid accumulation via Oil Red O and Nile Red staining. mRNA levels of miR-200a-5p and lipid metabolism genes were measured with RT-PCR, and AMPK, p-AMPK, and SERCA2b protein levels were analyzed by Western blotting. The interaction between miR-200a-5p and AMPK was studied using a luciferase reporter assay. A high-fat diet-induced MASLD mouse model was used to evaluate metformin's effects on liver steatosis and lipid profiles. Serum miR-200a-5p levels were also analyzed in MASLD patients.

In the PA cell model, elevated miR-200a-5p and lipid metabolism gene mRNA levels were observed, with decreased AMPK and SERCA2b protein levels. miR-200a-5p mimic reduced AMPK and SERCA2b expression. Metformin treatment reduced liver steatosis and lipid deposition in mice, normalizing miR-200a-5p, lipid metabolism gene mRNA, and AMPK/SERCA2b protein levels. Elevated serum miR-200a-5p was detected in MASLD patients.

These findings suggest that metformin alleviates lipid deposition and ER stress in MASLD through the modulation of the AMPK/SERCA2b pathway via miR-200a-5p.

Gout is a disease caused by hyperuricemia, characterized by inflammation reactions triggered by macrophage polarization. Colchicine is a commonly used drug for gout treatment, but its mechanism of action remains unclear. The aim of this study was to investigate the regulatory effect of colchicine on macrophage polarization to enhance the therapeutic effectiveness against gout inflammation. To accomplish this, a mouse model was established, and peripheral blood mononuclear cell samples were collected. Single-cell RNA sequencing was employed to reveal cellular heterogeneity and identify key genes. Molecular docking and experimental validation were performed to confirm the binding between the key genes and colchicine. Lentiviral intervention and biochemical indicator detection were conducted to assess the impact of key genes on gout mice. Additionally, the therapeutic effect of colchicine incorporated into neutrophil membrane-coated nanoparticles was investigated. The study found that macrophage polarization plays a critical role in gout, and AHNAK was identified as the key gene through which colchicine affects macrophage polarization. Lentiviral intervention to decrease AHNAK expression was shown to alleviate joint swelling in gout mice and regulate macrophage polarization. Colchicine encapsulated in R4F peptide-modified neutrophil membrane-coated Pluronic F127 nanoparticle (R4F-NM@F127) nanocarriers inhibited M1 macrophage polarization, induced M2 macrophage polarization, alleviated gout, and minimized toxicity to normal tissues. Colchicine suppressed M1 macrophage polarization and induced M2 macrophage polarization by binding to AHNAK protein, thereby alleviating gout. Colchicine incorporated into R4F-NM@F127 nanocarriers can serve as a targeted therapeutic drug to regulate macrophage polarization, alleviate gout, and reduce toxicity to normal tissues.

Cardiovascular disorders (CVDs) are a major global health concern, but their underlying molecular mechanisms are not fully understood. Recent research highlights the role of long noncoding RNAs (lncRNAs), particularly ANRIL, in cardiovascular development and disease. ANRIL, located in the human genome's 9p21 region, significantly regulates cardiovascular pathogenesis. It controls nearby tumor suppressor genes CDKN2A/B through epigenetic pathways, influencing cell growth and senescence. ANRIL interacts with epigenetic modifiers, leading to altered histone modifications and gene expression changes. It also acts as a transcriptional regulator, impacting key genes in CVD development. ANRIL's involvement in cardiovascular epigenetic regulation suggests potential therapeutic strategies. Manipulating ANRIL and its associated epigenetic modifiers could offer new approaches to managing CVDs and preventing their progression. Dysregulation of ANRIL has been linked to various cardiovascular conditions, including coronary artery disease, atherosclerosis, ischemic stroke, and myocardial infarction. This abstract provides insights from recent research, emphasizing ANRIL's significance in the epigenetic landscape of cardiovascular disorders. By shedding light on ANRIL's role in cellular processes and disease development, the abstract highlights its potential as a therapeutic target for addressing CVDs.

The suppression of the fibroblast growth factor 21/fibroblast growth factor receptor 1 (FGF21/FGFR1) signaling pathway is considered as a vital factor in the type 2 diabetes mellitus (T2DM) progression. Our previous study showed that gentiopicroside (GPS), the main active compound present in Gentiana macrophylla Pall., has the capacity to control disorders related to glucose and lipid metabolism in individuals with T2DM. Nevertheless, the specific mechanism remains unclear.

In light of the fact that the PharmMapper database suggests FGFR1 as the target of GPS, our investigation aims to determine if GPS can enhance glucose and lipid metabolism issues in T2DM by modulating the FGF21/FGFR1 signaling pathway.

In this study, we used palmitic acid (PA)-induced HepG2 cells and db/db mice to investigate the function and mechanism of GPS in the FGF21/FGFR1 signaling pathway. To examine the interaction between GPS and FGFR1, researchers performed Cellular Thermal Shift Assay (CETSA) and Surface Plasmon Resonance (SPR) analysis.

The results suggest that GPS activates the traditional metabolic pathways, including PI3K/AKT and AMPK, which are the subsequent stages of the FGF21/FGFR1 pathway. This activation leads to the enhancement of glucose and lipid metabolism issues in PA-treated HepG2 cells and db/db mice. Furthermore, the depletion of FGFR1 has been noticed to oppose the stimulation of PI3K/AKT and AMPK pathways by GPS in HepG2 cells subjected to PA. Notability, our research affirms that GPS binds directly to FGFR1, hindering the ubiquitinated degradation of FGFR1 by neural precursor cells expressing developmentally decreased protein 4 (NEDD4) and ultimately promoting FGF21 signal transduction.

This study demonstrates that GPS targeting FGFR1 activates the PI3K/AKT and AMPK pathways, which is an important mechanism for its treatment of T2DM.

Aging leads to a gradual decline in kidney function, making the kidneys increasingly vulnerable to various diseases. Oxidative stress, together with cellular senescence, has been established as paramount in promoting the aging process of the kidney. Oxidative stress, defined as an imbalance between ROS formation and antioxidant defense mechanisms, has been implicated in the kidney's cellular injury, inflammation, and premature senescence. Concurrently, the accumulation of SCs in the kidney also exacerbates oxidative stress via the secretion of pro-inflammatory and tissue-damaging factors as the senescence-associated secretory phenotype (SASP). Recently, SIRT1, a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, has been pivotal in combating oxidative stress and cellular senescence in the aging kidney. SIRT1 acts as a potential antioxidant molecule through myriad pathways that influence diverse transcription factors and enzymes essential in maintaining redox homeostasis. SIRT1 promotes longevity and renal health by modulating the acetylation of cell cycle and senescence pathways. This review covers the complex relationship between oxidative stress and cellular senescence in the aging kidney, emphasizing the protective role of SIRT1. See also the graphical abstract(Fig. 1).

Macrophages are versatile immune cells with remarkable plasticity, enabling them to adapt to diverse tissue microenvironments and perform various functions. Traditionally categorized into classically activated (M1) and alternatively activated (M2) phenotypes, recent advances have revealed a spectrum of macrophage activation states that extend beyond this dichotomy. The complex interplay of signaling pathways, transcriptional regulators, and epigenetic modifications orchestrates macrophage polarization, allowing them to respond to various stimuli dynamically. Here, we provide a comprehensive overview of the signaling cascades governing macrophage plasticity, focusing on the roles of Toll-like receptors, signal transducer and activator of transcription proteins, nuclear receptors, and microRNAs. We also discuss the emerging concepts of macrophage metabolic reprogramming and trained immunity, contributing to their functional adaptability. Macrophage plasticity plays a pivotal role in tissue repair and regeneration, with macrophages coordinating inflammation, angiogenesis, and matrix remodeling to restore tissue homeostasis. By harnessing the potential of macrophage plasticity, novel therapeutic strategies targeting macrophage polarization could be developed for various diseases, including chronic wounds, fibrotic disorders, and inflammatory conditions. Ultimately, a deeper understanding of the molecular mechanisms underpinning macrophage plasticity will pave the way for innovative regenerative medicine and tissue engineering approaches.

This study aims to analyze the efficacy of metformin on carotid intima media thickness (CIMT) and flow-mediated dilation (FMD) for patients with polycystic ovary syndrome (PCOS).

A literature search of PubMed, Embase, and the Cochrane Library from inception to December 2023 was conducted. Then, after studies selection and data extraction, the mean difference (MD) with a 95% confidence interval (CI) was used to evaluate metformin efficacy in CIMT and FMD for PCOS patients. Heterogeneity was investigated through subgroup and sensitivity analysis. The protocol of our study has been registered in PROSPERO (CRD42024497239).

A total of 12 studies with 248 patients were included. CIMT was lower in the endpoint group (after metformin) compared with the baseline group (before metformin) (MD = -0.11, 95% CI = -0.21 to -0.01, p = 0.04). FMD was higher in the endpoint group compared with the baseline group (MD = 3.25, 95% CI = 1.85 to 4.66, p < 0.01). No statistically significant difference was observed in nitroglycerin-mediated dilation (NMD) between the two groups (MD = 0.65, p = 0.51). Subgroup analysis showed that a relatively lower MD of CIMT in PCOS patients from Europe in the endpoint group compared with the baseline group (MD = -0.09, 95% CI = -0.14 to -0.04, p < 0.001). However, the MD in CIMT was not significantly different between the endpoint group and baseline group in PCOS patients from Asia (p = 0.270).

Metformin may have a beneficial effect on CIMT and FMD, but not on NMD, suggesting that metformin may help reduce cardiovascular events in PCOS patients. Notably, the clinical efficacy of metformin can be influenced by regional differences and study types.

There is increasing evidence that macrophages are involved in the development of carotid atherosclerosis (CAS), but the specific mechanism is still unclear. We aimed to explore the key genes that play a regulatory role on macrophages in the progression of CAS.

From 2021 August to 2023 August, GEO datasets GSE100927 and GSE43292 were downloaded and the key gene modules related to CAS were identified by weighted Gene co-expression network analysis (WGCNA). Kyoto Encyclopedia of Genes and Genes (KEGG) pathway analysis was performed on the genes of the key modules to identify common gene enrichment pathways. Differential expression analysis of pathway-related genes was performed by the "limma" package of R software. Case groups were categorized into high and low expression groups based on the expression levels of key genes, and ssGSEA immune infiltration analysis was performed.

The turquoise module of GSE100924 (threshold=12) and the brown module of GSE43292 (threshold=7) were obtained through WGCNA analysis. The analysis of KEGG showed that the differentially expressed genes in the turquoise and brown modules were co-enriched in the staphylococcus aureus infection signaling pathway. Differential expression analysis identified 18 common differentially expressed genes, all of which were highly expressed in the case group. C1QA is the gene of interest. According to ssGSEA analysis, the high expression group of C1QA showed a significant increase in the number of macrophages (GSE43292, P=0.0011; GSE100927, P=0.025).

This study identified the key gene C1QA involved in regulating macrophage functional activity during the CAS process, providing new ideas for effective control of CAS.

Background: Although xenografts have shown successful results in GBR procedures due to their osteoconductive properties, many authors have opted to add co-adjuvant drugs to favor osteogenesis and differentiate cells into an osteoblastic lineage. Metformin has been shown to have bone-protective properties, regulating osteoclast differentiation, as well as the ability to promote osteoblast mineralization and differentiation. The present study aimed to evaluate the effect of the local application of a 1% metformin solution on bone neoformation in the treatment of an experimental bone defect in a guided bone regeneration animal model with a particulated bovine hydroxyapatite xenograft with hyaluronate. Methods: With this purpose in mind, two critical defects with 8 mm diameter and 0.5 mm depth were created in eight male New Zealand rabbit calvarias. Titanium cylinders were fixed in each defect and filled with particulate hydroxyapatite of bovine origin and sodium hyaluronate, with sterile injectable saline added to the control group and sterile 1% metformin solution added to the test group. At 6 weeks, the animals were euthanized, and samples were obtained and prepared for histomorphometric analysis. Results: A higher percentage of new bone formation was observed in the metformin samples than in the control samples, both in the region closest to the animal's calvaria and in the most distal region analyzed. A higher average bone-biomaterial contact percentage was observed in the samples, with metformin in both the proximal and distal regions. There was no statistically significant difference in the mean value in either region in both parameters. Conclusion: The local application of a 1% metformin solution in an animal model of guided bone regeneration with particulate bovine hydroxyapatite and hyaluronate resulted in greater bone neoformation and xenograft osseointegration than in the control group.

Tuberculosis (TB) remains a leading cause of death among infectious diseases, particularly in poor countries. Viral infections, multidrug-resistant and ex-tensively drug-resistant TB strains, as well as the coexistence of chronic illnesses such as diabetes mellitus (DM) greatly aggravate TB morbidity and mortality. DM [particularly type 2 DM (T2DM)] and TB have converged making their control even more challenging. Two contemporary global epidemics, TB-DM behaves like a syndemic, a synergistic confluence of two highly prevalent diseases. T2DM is a risk factor for developing more severe forms of multi-drug resistant-TB and TB recurrence after preventive treatment. Since a bidirectional relationship exists between TB and DM, it is necessary to concurrently treat both, and promote recommendations for the joint management of both diseases. There are also some drug-drug interactions resulting in adverse treatment outcomes in TB-DM patients including treatment failure, and reinfection. In addition, autophagy may play a role in these comorbidities. Therefore, the TB-DM comorbidities present several health challenges, requiring a focus on multidisciplinary collaboration and integrated strategies, to effectively deal with this double burden. To effectively manage the comorbidity, further screening in affected countries, more suitable drugs, and better treatment strategies are required.

Diabetic heart disease (DHD) is a serious complication in patients with diabetes. Despite numerous studies on the pathogenic mechanisms and therapeutic targets of DHD, effective means of prevention and treatment are still lacking. The pathogenic mechanisms of DHD include cardiac inflammation, insulin resistance, myocardial fibrosis, and oxidative stress. Macrophages, the primary cells of the human innate immune system, contribute significantly to these pathological processes, playing an important role in human disease and health. Therefore, drugs targeting macrophages hold great promise for the treatment of DHD. In this review, we examine how macrophages contribute to the development of DHD and which drugs could potentially be used to target macrophages in the treatment of DHD.

Atherosclerosis (AS), a lipid-induced inflammatory condition of the arteries, is a primary contributor to atherosclerotic cardiovascular diseases including stroke. Arctium lappa L. leaf (ALL), an edible and medicinal herb in China, has been documented and commonly used for treating stroke since the ancient times. However, the elucidations on its anti-AS effects and molecular mechanism remain insufficient.

To investigate the AS-ameliorating effects and the underlying mechanism of action of an ethanolic extract of leaves of Arctium lappa L. (ALLE).

ALLE was reflux extracted using with 70% ethanol. An HPLC method was established to monitor the quality of ALLE. High fat diet (HFD) and vitamin D3-induced experimental AS in rats were used to determine the in vivo effects; and oxidized low-density lipoprotein-induced RAW264.7 macrophage foam cells were used for in vitro assays. Simvatatin was used as positive control. Biochemical assays were implemented to ascertain the secretions of lipids and pro-inflammatory mediators. Haematoxylin-eosin (H&E) and Oil red O stains were employed to assess histopathological alterations and lipid accumulation conditions, respectively. CCK-8 assays were used to measure cytotoxicity. Immunoblotting assay was conducted to measure protein levels.

ALLE treatment significantly ameliorated lipid deposition and histological abnormalities of aortas and livers in AS rats; improved the imbalances of serum lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C); notably attenuated serum concentrations of inflammation-associated cytokines/molecules including TNF-α, IL-6, IL-1β, VCAM-1, ICAM-1and MMP-9. Mechanistic studies demonstrated that ALLE suppressed the phosphorylation/activation of PI3K, Akt and NF-κB in AS rat aortas and in cultured foam cells. Additionally, the PI3K agonist 740Y-P notably reversed the in vitro inhibitory effects of ALLE on lipid deposition, productions of TC, TNF-α and IL-6, and protein levels of molecules of PI3K/Akt and NF-κB singnaling pathways.

ALLE ameliorates HFD- and vitamin D3-induced experimental AS by modulating lipid metabolism and inflammatory responses, and underlying mechanisms involves inhibition of the PI3K/Akt and NF-κB singnaling pathways. The findings of this study provide scientific justifications for the traditional application of ALL in managing atherosclerotic diseases.

In recent years, the role of cellular metabolism in immunity has come into the focus of many studies. These processes form a basis for the maintenance of tissue integrity and homeostasis, as well as represent an integral part of the immune response, in particular, inflammation. Metabolic adaptations not only ensure energy supply for immune response, but also affect the functions of immune cells by controlling transcriptional and post-transcriptional programs. Studying the immune cell metabolism facilitates the search for new treatment approaches, especially for metabolic disorders. Macrophages, innate immune cells, are characterized by a high functional plasticity and play a key role in homeostasis and inflammation. Depending on the phenotype and origin, they can either perform various regulatory functions or promote inflammation state, thus exacerbating the pathological condition. Furthermore, their adaptations to the tissue-specific microenvironment influence the intensity and type of immune response. The review examines the effect of metabolic reprogramming in macrophages on the functional activity of these cells and their polarization. The role of immunometabolic adaptations of myeloid cells in tissue homeostasis and in various pathological processes in the context of inflammatory and metabolic diseases is specifically discussed. Finally, modulation of the macrophage metabolism-related mechanisms reviewed as a potential therapeutic approach.

Fatty acid-binding protein 4 (FABP4) plays a role in lipid metabolism and cardiovascular health. In this paper, we cover FABP4 biology, its implications in atherosclerosis from observational studies, genetic factors affecting FABP4 serum levels, and ongoing drug development to target FABP4 and offer insights into future FABP4 research.

FABP4 impacts cells through JAK2/STAT2 and c-kit pathways, increasing inflammatory and adhesion-related proteins. In addition, FABP4 induces angiogenesis and vascular smooth muscle cell proliferation and migration. FABP4 is established as a reliable predictive biomarker for cardiovascular disease in specific at-risk groups. Genetic studies robustly link PPARG and FABP4 variants to FABP4 serum levels. Considering the potential effects on atherosclerotic lesion development, drug discovery programs have been initiated in search for potent inhibitors of FABP4. Elevated FABP4 levels indicate an increased cardiovascular risk and is causally related to acceleration of atherosclerotic disease, However, clinical trials for FABP4 inhibition are lacking, possibly due to concerns about available compounds' side effects. Further research on FABP4 genetics and its putative causal role in cardiovascular disease is needed, particularly in aging subgroups.

Macrophages are crucial cells in the human body's innate immunity and are engaged in a variety of non-inflammatory reactions. Macrophages can develop into two kinds when stimulated by distinct internal environments: pro-inflammatory M1-like macrophages and anti-inflammatory M2-type macrophages. During inflammation, the two kinds of macrophages are activated alternatively, and maintaining a reasonably steady ratio is critical for maintaining homeostasis in vivo. M1 macrophages can induce inflammation, but M2 macrophages suppress it. The imbalance between the two kinds of macrophages will have a significant impact on the illness process. As a result, there are an increasing number of research being conducted on relieving or curing illnesses by altering the amount of macrophages. This review summarizes the role of macrophage polarization in various inflammatory diseases, including autoimmune diseases (RA, EAE, MS, AIH, IBD, CD), allergic diseases (allergic rhinitis, allergic dermatitis, allergic asthma), atherosclerosis, obesity and type 2 diabetes, metabolic homeostasis, and the compounds or drugs that have been discovered or applied to the treatment of these diseases by targeting macrophage polarization.

Cancer continues to pose a significant global health challenge, as evidenced by the increasing incidence rates and high mortality rates, despite the advancements made in chemotherapy. The emergence of chemoresistance further complicates the effectiveness of treatment. However, there is growing interest in the potential of metformin, a commonly prescribed drug for type 2 diabetes mellitus (T2DM), as an adjuvant chemotherapy agent in cancer treatment. Although the precise mechanism of action of metformin in cancer therapy is not fully understood, it has been found to have pleiotropic effects, including the modulation of metabolic pathways, reduction in inflammation, and the regulation of cellular proliferation. This comprehensive review examines the anticancer properties of metformin, drawing insights from various studies conducted in vitro and in vivo, as well as from clinical trials and observational research. This review discusses the mechanisms of action involving both insulin-dependent and independent pathways, shedding light on the potential of metformin as a therapeutic agent for different types of cancer. Despite promising findings, there are challenges that need to be addressed, such as conflicting outcomes in clinical trials, considerations regarding dosing, and the development of resistance. These challenges highlight the importance of further research to fully harness the therapeutic potential of metformin in cancer treatment. The aims of this review are to provide a contemporary understanding of the role of metformin in cancer therapy and identify areas for future exploration in the pursuit of effective anticancer strategies.

Given its increasing prevalence, aging is of great concern to researchers worldwide. Cellular senescence is a physiological or pathological cellular state caused by aging and a prominent risk factor for the interruption of the integrity and functionality of human biological barriers. Health barriers play an important role in maintaining microenvironmental homeostasis within the body. The senescence of barrier cells leads to barrier dysfunction and age-related diseases. Cellular senescence has been reported to be a key target for the prevention of age-related barrier diseases, including Alzheimer's disease, Parkinson's disease, age-related macular degeneration, diabetic retinopathy, and preeclampsia. Drugs such as metformin, dasatinib, quercetin, BCL-2 inhibitors, and rapamycin have been shown to intervene in cellular senescence and age-related diseases. In this review, we conclude that cellular senescence is involved in age-related biological barrier impairment. We further outline the cellular pathways and mechanisms underlying barrier impairment caused by cellular senescence and describe age-related barrier diseases associated with senescent cells. Finally, we summarize the currently used anti-senescence pharmacological interventions and discuss their therapeutic potential for preventing age-related barrier diseases.

Macrophages, a heterogeneous population of innate immune cells, exhibit remarkable plasticity and play pivotal roles in coordinating immune responses and maintaining tissue homeostasis within the context of metabolic diseases. The activation of inflammatory macrophages in obese adipose tissue leads to detrimental effects, inducing insulin resistance through increased inflammation, impaired thermogenesis, and adipose tissue fibrosis. Meanwhile, adipose tissue macrophages also play a beneficial role in maintaining adipose tissue homeostasis by regulating angiogenesis, facilitating the clearance of dead adipocytes, and promoting mitochondrial transfer. Exploring the heterogeneity of macrophages in obese adipose tissue is crucial for unraveling the pathogenesis of obesity and holds significant potential for targeted therapeutic interventions. Recently, the dual effects and some potential regulatory mechanisms of macrophages in adipose tissue have been elucidated using single-cell technology. In this review, we present a comprehensive overview of the intricate activation mechanisms and diverse functions of macrophages in adipose tissue during obesity, as well as explore the potential of drug delivery systems targeting macrophages, aiming to enhance the understanding of current regulatory mechanisms that may be potentially targeted for treating obesity or metabolic diseases.

Macrophage-driven immune dysfunction of the intestinal mucosa is involved in the pathophysiology of ulcerative colitis (UC). Emerging evidence indicates that there is an elevation in miR-31-5p levels in UC, which is accompanied by a downregulation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) expression. Nevertheless, the precise influence of miR-31-5p on macrophage polarization and the integrity of the intestinal epithelial barrier in UC remains to be fully elucidated. This study explored the role of miR-31-5p and AMPK in UC through a bioinformatics investigation. It investigated the potential of miR-31-5p antagomir to shift macrophages from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype and enhance the intestinal mucosal barrier in DSS-induced UC mice. Additionally, RAW264.7 cells stimulated with LPS were employed to confirm the reversal of miR-31-5p antagomir's therapeutic effect under AMPK inhibition. The findings demonstrated that miR-31-5p antagomir penetrated colonic tissues and ameliorated DSS-induced experimental colitis. Transformation of spleen and mesenteric lymph node macrophages from M1 to M2 type was seen in the DSS+miR-31-5p antagomir group. AMPK/Sirt1 expression increased while NLRP3 expression decreased. Expression of M2-related genes and proteins was enhanced and that of the M1 phenotype suppressed. Tight junction proteins, ZO-1 and occludin, were increased. The therapeutic effects of miR-31-5p antagomir transfection into RAW264.7 cells were repressed when AMPK expression was inhibited. Therefore, our results suggest that suppression of miR-31-5p expression transformed macrophages from M1 to M2, ameliorated inflammation and repaired the intestinal epithelium to alleviate DSS-induced colitis. AMPK/Sirt1/NLRP3 was involved.

Diabetes mellitus (DM) is increasing drastically and affecting the individuals globally, especially in the low- and middle-income countries like India. The poor glycaemic control results in micro-vascular and macro-vascular complications, leading to dysfunction of multiple organs. This study aimed to evaluate the association between the risk factors and microalbuminuria levels among patients with type 2 DM on oral hypoglycaemic agents.

Hundred type 2 DM patients fulfilling the inclusion and exclusion criteria were selected by convenient random sampling. Demographic details, biochemical markers, and anti-diabetic medication details were collected. The findings were analyzed statistically using Chi-square test and one-way analysis of variance (ANOVA) with SPSS software 21.0.

Among the different combination therapies, 59% were commonly using metformin and teneligliptin. There was a significant association noted between microalbuminuria and risk factors like age, duration of disease, body mass index (BMI) (25.5 ± 2.9), fasting blood sugar (151 ± 53.2 mg/dL), post prandial blood sugar (227.01 ± 70.9 mg/dL), blood urea (24.42 ± 9.3 mg/dL), and serum creatinine (1.5 ± 0.2 mg/dL) (P < 0.001). One-way ANOVA showed statistical significance between microalbuminuria and the different treatment groups (P < 0.0001).

Microalbuminuria was associated with age, duration of diabetes, glycaemic control, and BMI. In contrast, there was no significant difference noted between the genders and microalbuminuria. Microalbuminuria is an early indication of nephropathy in diabetes patients. The early identification of the risk factors is important, and it is always recommended to screen for microalbuminuria in all the diabetic patients for early detection and prevention of diabetic nephropathy and their associated complications.

Metformin is a drug with a long history of providing benefits in diabetes management and beyond. The mechanisms of action of metformin are complex, and continue to be actively debated and investigated. The aim of this study is to identify metabolic signatures associated with metformin treatment, which may explain the pleiotropic mechanisms by which metformin works, and could lead to an improved treatment and expanded use.

This is a cross-sectional study, in which clinical and metabolomic data for 146 patients with type 2 diabetes were retrieved from Qatar Biobank. Patients were categorized into: Metformin-treated, treatment naïve, and non-metformin treated. Orthogonal partial least square discriminate analysis and linear models were used to analyze differences in the level of metabolites between the metformin treated group with each of the other two groups.

Patients on metformin therapy showed, among other metabolites, a significant increase in 3-hydroxyoctanoate and 3-hydroxydecanoate, which may have substantial effects on metabolism.

This is the first study to report an association between 3-hydroxy medium chain fatty acids with metformin therapy in patients with type 2 diabetes. This opens up new directions towards repurposing metformin by comprehensively understanding the role of these metabolites.

Ferroptosis is a newly identified form of non-apoptotic programmed cell death, characterized by the iron-dependent accumulation of lethal lipid reactive oxygen species (ROS) and peroxidation of membrane polyunsaturated fatty acid phospholipids (PUFA-PLs). Ferroptosis is unique among other cell death modalities in many aspects. It is initiated by excessive oxidative damage due to iron overload and lipid peroxidation and compromised antioxidant defense systems, including the system Xc-/ glutathione (GSH)/glutathione peroxidase 4 (GPX4) pathway and the GPX4-independent pathways. In the past ten years, ferroptosis was reported to play a critical role in the pathogenesis of various cardiovascular diseases, e.g., atherosclerosis (AS), arrhythmia, heart failure, diabetic cardiomyopathy, and myocardial ischemia-reperfusion injury. Studies have identified dysfunctional iron metabolism and abnormal expression profiles of ferroptosis-related factors, including iron, GSH, GPX4, ferroportin (FPN), and SLC7A11 (xCT), as critical indicators for atherogenesis. Moreover, ferroptosis in plaque cells, i.e., vascular endothelial cell (VEC), macrophage, and vascular smooth muscle cell (VSMC), positively correlate with atherosclerotic plaque development. Many macromolecules, drugs, Chinese herbs, and food extracts can inhibit the atherogenic process by suppressing the ferroptosis of plaque cells. In contrast, some ferroptosis inducers have significant pro-atherogenic effects. However, the mechanisms through which ferroptosis affects the progression of AS still need to be well-known. This review summarizes the molecular mechanisms of ferroptosis and their emerging role in AS, aimed at providing novel, promising druggable targets for anti-AS therapy.

Presently, the mechanism of occurrence and development of vascular calcification (VC) is not fully understood; a range of evidence suggests a positive association between diabetes mellitus (DM) and VC. Furthermore, the increasing burden of central vascular disease in patients with chronic kidney disease (CKD) may be due, at least in part, to VC. In this review, we will review recent advances in the mechanisms of VC in the context of CKD and diabetes. The study further unveiled that VC is induced through the stimulation of pro-inflammatory factors, which in turn impairs endothelial function and triggers similar mechanisms in both disease contexts. Notably, hyperglycemia was identified as the distinctive mechanism driving calcification in DM. Conversely, in CKD, calcification is facilitated by mechanisms including mineral metabolism imbalance and the presence of uremic toxins. Additionally, we underscore the significance of investigating vascular alterations and newly identified molecular pathways as potential avenues for therapeutic intervention.

Breast cancer is the most prevalent cancer worldwide and its incidence increases with age, posing a significant threat to women's health globally. Due to the clinical heterogeneity of breast cancer, the majority of patients develop drug resistance and metastasis following treatment. Ferroptosis, a form of programmed cell death dependent on iron, is characterized by the accumulation of lipid peroxides, elevated levels of iron ions and lipid peroxidation. The underlying mechanisms and signalling pathways associated with ferroptosis are intricate and interconnected, involving various proteins and enzymes such as the cystine/glutamate antiporter, glutathione peroxidase 4, ferroptosis inhibitor 1 and dihydroorotate dehydrogenase. Consequently, emerging research suggests that ferroptosis may offer a novel target for breast cancer treatment; however, the mechanisms of ferroptosis in breast cancer urgently require resolution. Additionally, certain natural compounds have been reported to induce ferroptosis, thereby interfering with breast cancer. Therefore, this review not only discusses the molecular mechanisms of multiple signalling pathways that mediate ferroptosis in breast cancer (including metastasis, invasion and proliferation) but also elaborates on the mechanisms by which natural compounds induce ferroptosis in breast cancer. Furthermore, this review summarizes potential compound types that may serve as ferroptosis inducers in future tumour cells, providing lead compounds for the development of ferroptosis-inducing agents. Last, this review proposes the potential synergy of combining natural compounds with traditional breast cancer drugs in the treatment of breast cancer, thereby suggesting future directions and offering new insights.

The objective of this study is to compare a series of albumin-based folate radiotracers for the potential imaging of folate receptor (FR) positive macrophages in advanced atherosclerotic plaques. Diversified radioiodinated FR-targeting albumin-binding probes ([131I]IBAbHF, [131I]IBNHF, and [131I]HF) were developed through various strategies. Among the three radiotracers, [131I]IBAbHF and [131I]IBNHF showed excellent in vitro stability (>98%) in saline and PBS 7.4 for 24 h. Also, good stability of [131I]IBNHF in mouse serum albumin was monitored using an HSA ELISA kit. The experiments in Raw264.7 macrophages activated by ox-LDL confirmed the specificity of tracers for FR-β. Biodistribution studies of radiotracers were performed to verify the prolonged blood half-life. Prolonged blood half-lives of [131I]IBAbHF, [131I]HF, and [131I]IBNHF were 17.26 ± 4.29, 6.33 ± 2.64, and 5.50 ± 1.26 h, respectively. SPECT-CT imaging of ApoE-/- mice at different stages was performed to evaluate the progression and monitor the prognosis of AS. Evident [131I]IBNHF uptake in atherosclerotic lesions could be observed along with a low background signal. In summary, we demonstrated a proof-of-concept of albumin-based radioligands for FR-targeting atherosclerosis imaging and found that different incorporation of radioiodinated groups resulted in different pharmacokinetic properties. Among these candidate compounds, [131I]IBNHF would be a satisfactory radiotracer for SPECT imaging of atherosclerosis.

AMP-activated protein kinase (AMPK) is a ubiquitous sensor of energy and nutritional status in eukaryotic cells. It plays a key role in regulating cellular energy homeostasis and multiple aspects of cell metabolism. During macrophage polarisation, AMPK not only guides the metabolic programming of macrophages, but also counter-regulates the inflammatory function of macrophages and promotes their polarisation toward the anti-inflammatory phenotype. AMPK is located at the intersection of macrophage metabolism and inflammation. The metabolic characteristics of macrophages are closely related to immune-related diseases, infectious diseases, cancer progression and immunotherapy. This review discusses the structure of AMPK and its role in the metabolism, function and polarisation of macrophages. In addition, it summarises the important role of the AMPK pathway and AMPK activators in the development of macrophage-related diseases.

Atherosclerosis is a common cardiovascular disease caused by the abnormal expression of multiple factors and genes influenced by both environmental and genetic factors. The primary manifestation of atherosclerosis is plaque formation, which occurs when inflammatory cells consume excess lipids, affecting their retention and modification within the arterial intima. This triggers endothelial cell (EC) activation, immune cell infiltration, vascular smooth muscle cell (VSMC) proliferation and migration, foam cell formation, lipid streaks, and fibrous plaque development. These processes can lead to vascular wall sclerosis, lumen stenosis, and thrombosis. Immune cells, ECs, and VSMCs in atherosclerotic plaques undergo significant metabolic changes and inflammatory responses. The interaction of cytokines and chemokines secreted by these cells leads to the onset, progression, and regression of atherosclerosis. The regulation of cell- or cytokine-based immune responses is a novel therapeutic approach for atherosclerosis. Statins are currently the primary pharmacological agents utilised for managing unstable plaques owing to their ability to enhance endothelial function, regulate VSMC proliferation and apoptosis by reducing cholesterol levels, and mitigate the expression and activity of inflammatory cytokines. In this review, we provide an overview of the metabolic changes associated with atherosclerosis, describe the effects of inflammatory responses on atherosclerotic plaques, and discuss the mechanisms through which statins contribute to plaque stabilisation. Additionally, we examine the role of statins in combination with other drugs in the management of atherosclerosis.

Characterize the risk of cardiovascular disease (CVD) in individuals with polycystic ovarian syndrome (PCOS). Review the pathophysiological pathways that confers CVD risk in individuals with PCOS and interventions to reduce CVD risk.

PCOS is a complex syndrome characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries that has metabolic and cardiovascular implications. Intrinsic hormonal dysregulation and chronic low-grade inflammation play an important role in the progression of atherosclerosis in young premenopausal individuals and development of CVD independently of associated traditional risk factors. Management with metformin reduces CVD risk by reducing atherosclerosis progression. PCOS is an important CVD risk factor among individuals of reproductive age. Early detection and interventions are needed to mitigate development of CVD.