[This retracts the article DOI: 10.1016/j.isci.2024.109502.].

Coronary heart disease (CHD) is a severe diabetic vascular complication and the main cause of mortality among diabetes patients. Early diagnosis of CHD could prevent its development. Both omentin-1 (Oment-1) and the long noncoding RNA MALAT1 (lncRNA MALAT1) can be detected in peripheral blood and exhibit protective or detrimental effects on CHD. However, whether these two factors could be predictive of CHD in T2DM patients remains unclear. Therefore, this study aimed to investigate the associations of circulating Oment-1 levels and the expression of MALAT1 with CHD in T2DM patients and to assess their predictive efficacy. A total of 137 T2DM patients were enrolled, including 68 patients without CHD (T2DM group) and 69 patients with CHD (T2DM + CHD group). Clinical parameters were collected, and plasma Oment-1 was measured by enzyme-linked immunosorbent assay (ELISA). RNA was isolated from peripheral monocytes, and the expression of MALAT1 was determined by quantitative PCR. Cardiac function was measured by echocardiography. Compared with that in T2DM patients, the plasma Oment-1 level was significantly lower, while the expression of MALAT1 was significantly greater in T2DM + CHD patients (all P values < 0.01). Bivariate correlation analysis indicated that Oment-1 was positively correlated with the left ventricular ejection fraction (LVEF) (P < 0.01). MALAT1 expression was negatively correlated with LVEF but positively correlated with age and DM duration (P < 0.05). Binary logistic regression suggested that Oment-1 and MALAT1 were significantly associated with the presence of CHD. Receiver operating characteristic (ROC) curve analysis demonstrated that both Oment-1 (AUC = 0.663, sensitivity = 75%, specificity = 49%) and MALAT1 (AUC = 0.749, sensitivity = 73%, specificity = 66%) had significant diagnostic value for CHD among T2DM patients. Notably, the combination of Oment-1 and MALAT1 exhibited better diagnostic efficiency (AUC = 0.771, sensitivity = 66.7%, specificity = 75.3%). In conclusion, decreased circulating Oment-1 levels and increased MALAT1 expression are closely associated with CHD in T2DM patients, and their combination offers superior diagnostic efficiency, suggesting Oment-1 and MALAT1 may serve as a non-invasive tool for the early CHD detection and risk stratification in high-risk T2DM patients. Further studies are warranted to explore the pathophysiological mechanisms of Omentin-1 and MALAT1 in the pathogenesis of CHD in T2DM and to validate their clinical utility as potential biomarkers in large cohort studies.

Rheumatoid arthritis (RA) is a chronic autoimmune disease causing joint inflammation, dysfunction, and deformity, along with systemic inflammatory manifestations. Inhibitor of differentiation-2 (ID2) is a transcription factor containing a helix-loop-helix (HLH) structure. Studies suggest that ID2 regulates innate and adaptive immunity and inhibits the differentiation of osteoclasts. However, the effects and underlying molecular mechanisms of ID2 on rheumatoid arthritis (RA) remain unclear. In the present study, we found that exogenous supplementation of human recombinant ID2 (hID2) protein significantly reduced paw swelling and arthritis index scores in adjuvant-induced arthritis (AIA) rats, and improved ankle joint pathology. Analysis of pro-inflammatory factor levels in peripheral blood mononuclear cells and synovial tissues indicated that hID2 attenuated inflammatory responses in AIA rats. Furthermore, RNA sequencing demonstrated that hID2 down-regulated the JAK-STAT pathway, and the phosphorylation of its key molecule, Signal Transducer and Activator of Transcription 3 (STAT3), was inhibited in synovial tissues. Additionally, the expression of chemokine-related genes was noticeably down-regulated in synovial tissues, though further investigation is needed to understand the underlying mechanisms. Overall, these findings suggest that hID2 effectively attenuated the inflammatory response and joint destruction in AIA rats, highlighting the potential of hID2 as a therapeutic agent for the treatment of RA.

Aortic dissection/aneurysm (AAD) is a critical and life-threatening condition marked by a lack of effective pharmacological treatments. Gene therapy has emerged as a promising approach to treat AAD and slow its advancement. However, the clinical utility of gene therapy is impeded by significant challenges, including the scarcity of innovative genetic drugs in current medical practices and the absence of a streamlined gene delivery mechanism. Our investigation centered on a unique gene target, tRF-Gly-CCC, belonging to tsRNAs, essential for maintaining vascular smooth muscle cell function and regulating inflammatory cell responses. To enhance in vivo treatment, we developed a kind of activated neutrophil membrane bionic nanoparticles (neu MCs), incorporating tRF-Gly-CCC-loaded polymer nanoparticles as the core and activated neutrophil membrane as the outer layer. The utilization of activated neutrophil membrane cloaking serves a dual purpose by safeguarding tRF-Gly-CCC and facilitating targeted delivery to the AAD site. Neu MCs exhibit improved stability in circulation, enabling precise delivery to aortic lesions and reducing AAD mortality. Notably, studies suggest that neu MCs offer a superior approach for immediate intervention to reduce vascular rupture. In conclusion, our study utilized a novel genetic drug and an effective delivery system to enable early intervention in AAD.

Sensorineural deafness mainly occurs due to damage to hair cells, and advances in stem cell technology, especially the application of induced pluripotent stem cells (iPSCs) and adult stem cells, provides new possibilities for hair cell regeneration. This review describes the basic knowledge of stem cells and their important applications in regenerative medicine, as well as recent progress in stem cell research in the field of hair cell regeneration, especially the induced differentiation of hair-like cells. At the same time, we also point out the challenges facing current research, including differentiation efficiency, cell stability issues, and treatment safety and long-term efficacy considerations. Finally, we look forward to the direction of future research, and emphasize the importance of the cell differentiation mechanism, simulation of the inner ear microenvironment, safety assessment, and personalized treatment strategies. In conclusion, despite many challenges, stem cell technology has shown great potential in the field of hearing research and is expected to bring revolutionary treatment options for patients with sensorineural hearing loss in the future.

Sterol regulatory element binding protein-1c (SREBP-1c), which serves an essential role in the process of fat synthesis, is a key adjustment factor that regulates the dynamic balance of lipid metabolism. SREBP-1c activates the transcription of multiple genes encoding for enzymes involved in the synthesis of triglycerides (TG) and fatty acids (FA) and accelerates lipid synthesis. Previous analysis indicated that long non-coding RNA HCV regulated 1 (IncHR1) participates in lipid metabolism in vivo and regulates the level of SREBP-1c protein. However, the mechanism of IncHR1 in regulating SREBP-1c levels has not been revealed. In the present study, a fatty degeneration cell model was used to study how IncHR1 regulates the SREBP-1c protein at the cellular level. Furthermore TG accumulation was assessed according to morphological analysis. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detected the expression of SREBP-1c. An activator and an inhibitor of phosphoinositide 3-kinase/AKT phosphorylation (IGF-1 and LY294002, respectively) were used to study the effect of IncHR1 on this pathway. It was verified that IncHR1 regulated SREBP-1c levels and the phosphorylation of AKT in the steatosis cell model. Detailed molecular mechanisms mediated by IncHR1 were associated with the phosphorylation AKT/FoxO1 in Huh7 cell lines. Simultaneously, IncHR1 affected the location of FoxO1 inside and outside of the nucleus. Furthermore, the phosphorylation of PDK1 upstream of AKT was regulated through overexpression or knockdown IncHR1, as determined by western blotting. Taken together, these data show that IncHR1 inhibits SREBP-1c levels through the phosphorylation of the PDK1/AKT/FoxO1 axis.

After organ transplantation, patients require treatment with immunosuppressive drugs to prevent immune rejection and transplantation failure. Tacrolimus (FK506) is a widely used immunosuppressant known for its potent immunosuppressive effect and narrow therapeutic range. Monitoring of FK506 blood concentrations is essential to avoid nephrotoxicity. In this study, a novel FK506 nanomedicine (FK506 cochleates) was developed using a microfluidic method to reduce variability among individuals and improve drug safety. The particle size of FK506 cochleates was (183.3 +/- 1.4) nm, the zeta potential was-(39.28 +/- 2.12) mV, and the encapsulation efficiency was more than 85 %. Particle size of FK506 cochleates could be maintained for up to 12 weeks in freeze-dried powder form. Small-angle X-ray scattering (SAXS) experiment confirmed the formation of cochleates by adding calcium solution. In vitro release studies demonstrated a sustained-release profile of FK506 from the cochleates carrier. Furthermore, the cochleates carrier could protect FK506 from the influence of stomach acid and slowly release the drug in the intestine. After oral administration, FK506 cochleates exhibited sustained- release properties in rats, accumulating in the spleen and lymph nodes- key anatomical sites for FK506's pharmacological action. Importantly, FK506 cochleates significantly prolonged the survival time in the rabbit heart transplantation model while maintaining good safety profiles. In conclusion, the FK506 cochleates showed promising potential for enhancing drug safety in therapeutic organ transplantation.

RNA-binding proteins (RBPs) have emerged as crucial regulators of post-transcriptional processes, influencing the fate of RNA. This review delves into the biological functions of RBPs and their role in alternative splicing concerning atherosclerosis (AS), highlighting their participation in essential cellular processes. Our goal is to offer new insights for cardiovascular disease research and treatment. Dysregulation of RBPs is associated with various human diseases, including autoimmune and neurological disorders. The role of RBPs in the pathogenesis of AS is progressively being elucidated, as they influence plaque formation and disease progression by regulating cell function and gene expression. RBPs play intricate biological roles in regulating pre-mRNA, including editing, splicing, stability and translation. Alternative splicing has been demonstrated to enhance biological complexity and diversity. Our findings indicate that alternative splicing is extensively involved in the pathogenesis of AS. The dysregulated expression of specific RBPs in AS is linked to the production of adhesion molecules and vascular endothelium damage. Further research on RBPs could pave the way for the development of novel therapeutic targets.

Constitutive explorations have demonstrated that circular RNAs (circRNAs) are closely related to cardiovascular diseases. However, few studies have identified regulatory roles of circRNAs in endothelial repair. In particular, circTMEM165 has first been reported to be highly expressed in hypoxic human umbilical vein endothelial cells (HUVECs), indicating it to be closely linked with endothelial functions and atherosclerosis. Here, we explored the main biological functions of circTMEM165 and its regulatory mechanism in atherosclerosis. We identified that circTMEM165 was downregulated in patients with atherosclerosis and negatively associated with atherosclerosis progression. Functionally, circTMEM165 was found to be abundant in endothelial cells, inhibiting inflammation and adhesion in HUVECs. Particularly, we first observed that lipopolysaccharide (LPS) could induce HUVEC apoptosis and mitochondrial fission, and circTMEM165 was later found to alleviate these effects. Mechanistically, circTMEM165, as a miR-192-3p sponge, upregulated the downstream expression of SCP2, which serves as critical regulator of biological functions of HUVECs. Moreover, the classic rat carotid artery balloon injury model demonstrated that circTMEM165 reduced apoptosis and intimal hyperplasia in vivo. These findings demonstrated the specific role of the circTMEM165/miR-192-3p/SCP2 pathway in regulating endothelial function and indicated that these molecules served as promising targets for the prediction and diagnosis of vascular diseases.Funding Information: This work was supported by The National Natural Science Foundation of China (grant no. 81870331), and The Qingdao municipal science and technology bureau project (grant no. 21-1-4-rkjk-12-nsh).Declaration of Interests: The authors declare no conflict of interest.Ethics Approval Statement: This study was approved by the Ethical Committee of Qingdao University and conducted in accordance with the Declaration of Helsinki. All human subjects provided signed informed consent. And the animal experiments approved by Qingdao University Laboratory Animal Welfare Ethics Committee (No. 201809SD18202012014).

This work aims to provide a novel reference for future diagnosis and treatment of synovitis of the knee joint (SKJ) by analyzing the correlation of the TLR4/MyD88 axis with the degree of inflammatory response in SKJ patients. First, this study retrospectively analyzed the clinical data of 46 SKJ patients (research group, RG) treated in our hospital from January 2021 to December 2022 and 52 concurrent healthy controls (control group, CG). Concentrations of TLR4, MyD88 and inflammatory factors (IFs) in peripheral blood were measured, and differences in TLR4 and MyD88 between groups were observed to explore the diagnostic performance of the two for SKJ. Additionally, the correlation of TLR4 and MyD88 with IFs and Western Ontario Mac Master (WOMAC) scores in SKJ patients was discussed. Through the above experiment, we found that TLR4 and MyD88 presented higher mRNA levels in RG than in CG (P<0.05), both of which had excellent diagnostic efficiency for SKJ. Pearson correlation coefficients identified a positive correlation of TLR4 and MyD88 mRNA with IFs and WOMAC scores (P<0.05). Therefore, The TLR4/MyD88 axis is activated in SKJ patients and is strongly related to the intensification of inflammatory responses.

AIM:To examine the role and mechanism of colorectal tumor differential expression (CRNDE) in brain injury induced by ischemicreperfusion.MATERIAL AND METHODS:Sh-SY5Y cells were cultured, and oxygen and glucose deprivation/reperfusion (OGD/R) injury tests were performed. The effects on SH-SY5Y cells were evaluated by the Cell Counting Kit-8 (CCK-8) assay, qPCR, apoptosis analysis, western blot analysis, ELISA, a luciferase reporter assay, and an RNA pull-down assay.RESULTS:Knockdown of CRBDE ameliorated SH-SY5Y cell impairment induced by OGD/R. CRNDE, the target of mir-489-3p, was directly bound to FOXO3. Mir-489-3p knockdown partially reversed OGD/R-mediated impairment in CRBDE knockdown SH-SY5Y cells.CONCLUSION:The results indicate that knockdown of lncRNA CRNDE ameliorates apoptosis and the inflammatory response in ischemia-reperfusion-induced brain injury through the mir-489-3p/FOXO3 axis. LncRNA CRNDE may represent a novel therapeutic target for brain injury.

Aortic dissection (AD) presents a medical challenge for clinicians. Here, to determine the role of a novel small non-coding piRNA-823 (piR-823) in AD, murine and human aorta from patients with AD were used. A high expression levels of piR-823 were found in patients with AD. Using performed loss- and gain-of-function assays in vitro and in vivo, we explore the regulatory effect of piR-823 on vascular smooth muscle cells (VSMCs) and AD. piR-823 obviously facilitates the proliferation, migration, and phenotypic transformation of VSMCs with or without nicotine treatment. piR-823 directly binds and suppresses histone deacetylase 1 (HDAC1) expression, and regulates the acetylation of histone 3 (H3) via H3K9ac and H3K27ac, eventually, VSMC functions and AD. To consolidate our findings, AD murine model was performed, and we observed that piR-823 antagomir strongly inhibited the pathogenesis of AD through regulating vascular remodeling. Thus, our study finds a potential target for the prevention and treatment strategy for nicotine-induced AD.

Background: Ginsenoside Rg2 (Rg2) has a variety of pharmacological activities and provides benefits during inflammation, cancer, and other diseases. However, there are no reports about the relationship between Rg2 and atherosclerosis.Methods: We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to detect the cell viability of Rg2 in vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs). The expression of inflammatory factors in HUVECs and the expression of phenotypic transformation-related marker in VSMCs were detected at mRNA levels. Western blot method was used to detect the expression of inflammation pathways and the expression of phenotypic transformation at the protein levels. The rat carotid balloon injury model was performed to explore the effect of Rg2 on inflammation and phenotypic transformation in vivo. Results: Rg2 decreased the expression of inflammatory factors induced by lipopolysaccharide in HUVECs-without affecting cell viability. These events depend on the blocking regulation of NF-KB and p-ERK signaling pathway. In VSMCs, Rg2 can inhibit the proliferation, migration, and phenotypic transformation of VSMCs induced by platelet derived growth factor-BB (PDGF-BB)-which may contribute to its anti-atherosclerotic role. In rats with carotid balloon injury, Rg2 can reduce intimal proliferation after injury, regulate the inflammatory pathway to reduce inflammatory response, and also suppress the phenotypic transformation of VSMCs.Conclusion: These results suggest that Rg2 can exert its anti-atherosclerotic effect at the cellular level and animal level, which provides a more sufficient basis for ginseng as a functional dietary regulator.(c) 2022 The Korean Society of Ginseng. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BACKGROUND:Aortic dissection (AD) is a lethal cardiac disorder and one of the most concerning cardiovascular diseases (CVDs). Increasing evidence indicates that human aortic vascular smooth muscle cells (VSMCs) play a crucial role in the pathogenesis of AD, especially related to phenotypic transformation. And notablely, the development of AD is also accompanied by inflammation.METHODS:By using quantitative real-time PCR and fluorescence in situ hybridization (FISH), we detected the expression levels of miR-564 in vitro and in vivo. The effects of miR-564 proliferation and migration were investigated in VSMCs. The downstream targets of miR-564 were found by bioinformatics analyse, and verified in the regulation on VSMCs. An AD murine model was constructed and clinical evaluation was performed to explore the critical roles of miR-564 in vivo. At the same time, the level of inflammation was detected using quantitative real-time PCR and immunofluorescence.RESULTS:Overexpression of miR-564 inhibited cell proliferation and migration, as well as phenotype switch, with or without platelet-derived growth factor BB (PDGF-BB) treatment, whereas downregulation of miR-564 led to opposite results. Mechanistically, miR-564 directly interacted with the target genes proto-oncogene (SKI) and neurogranin (NRGN) to regulate the biological functions of VSMCs. In particular, animal experiments demonstrated that miR-564 can alleviate the progression of AD mainly through mediating phenotypic swithing and inflammation which was consistent with clinical evaluation.CONCLUSIONS:Our study identified miR-564 as a significant molecule that attenuates AD progression by inhibiting inflammation and VSMCs proliferation, migration and phenotypic transformation, suggesting that it may be a potential therapeutic target for AD.

Due to many inconsistencies in differentially expressed genes (DEGs) related to genomic expression changes during keloid formation and a lack of satisfactory prevention and treatment methods for this disease, the critical biomarkers related to inflammation and the immune response affecting keloid formation should be systematically clarified. Normal skin/keloid scar tissue-derived fibroblast genome expression data sets were obtained from the Gene Expression Omnibus (GEO) and ArrayExpress databases. Hub genes have a high degree of connectivity and gene function aggregation in the integration network. The hub DEGs were screened by gene-related protein-protein interactions (PPIs), and their biological processes and signaling pathways were annotated to identify critical biomarkers. Finally, eighty-one hub DEGs were selected for further analysis, and some noteworthy signaling pathways and genes were found to be closely related to keloid fibrosis. For example, IL17RA is involved in IL-17 signal transduction, TIMP2 and MMP14 activate extracellular matrix metalloproteinases, and TNC, ITGB2, and ITGA4 interact with cell surface integrins. Furthermore, changes in local immune cell activity in keloid tissue were detected by DEG expression, immune cell infiltration, and mass CyTOF analyses. The results showed that CD4+ T cells, CD8+ T cells and NK cells were abnormal in keloid tissue compared with normal skin tissue. These findings not only support the key roles of fibrosis-related pathways, immune cells and critical genes in the pathogenesis of keloids but also expand our understanding of targets that may be useful for the treatment of fibrotic diseases.

Oral gene therapy has emerged as a potential optimal treatment for ulcerative colitis (UC). Nucleic acid drugs possessing versatility can not only inhibit inflammation but realize colon mucosal healing, fulfilling the clinical objective of UC therapy. However, the effective accumulation and distribution of oral nucleic acid drugs in the colon remain a considerable challenge. Furthermore, current delivery systems pay more attention to the accumulation of nucleic acid drugs in the colon, while the distribution of nucleic acid drugs in the colon, which plays a key role in the UC treatment, never catches the attention of researchers. Here, we used miR-320 as a model nucleic acid drug to develop a kind of multistage-responsive nanocomplexes (MSNs) based on polymeric nanocapsules and alginate. MSNs possess the pH responsiveness in the stomach, the enzyme responsiveness in the colonic lumen, and the redox responsiveness in the cytoplasm. In vivo imaging results showed that MSNs reach the colon within 2 h and effectively release miR-320 nanocapsules in the colonic lumen. The nanocapsules can further deliver miR-320 to the submucosal layer and even the muscular layer. Moreover, MSNs decreased the activity of myeloperoxidase and proinflammatory cytokines and exhibited anti-inflammatory activity by inhibiting the phosphorylation of IκBα and AKT, reducing colonic inflammation and enhancing mucosal repair. Therefore, MSNs can successfully alleviate UC by improving the accumulation and distribution of oral nucleic acid drugs in the colon, promoting the clinical translational application of nucleic acid drugs in the treatment of UC.

As one of the innate immune cells, macrophages play an important role in inflammation. Inflammation of the colon is mainly mediated by macrophages, which release a variety of inflammatory mediators via multiple mechanisms. Meanwhile, since macrophages are considered as the significant colitis regulators, increasing number of therapeutic drugs were developed to improve the symptoms of colitis, which provides new insights for the next clinical treatment. The purpose of this chapter is to summarize the role of macrophages in colitis and the potential targets with promising anticolitis effects and to emphasize the role of nucleotide-mediated immunotherapy to colitis, which could help people to find a better treatment strategy for colitis in future.

βII spectrin, the most common isoform of non-erythrocyte spectrin, is a cytoskeleton protein present in all nucleated cells. Interestingly, βII spectrin is essential for the development of various organs such as nerve, epithelium, inner ear, liver and heart. The functions of βII spectrin include not only establishing and maintaining the cell structure but also regulating a variety of cellular functions, such as cell apoptosis, cell adhesion, cell spreading and cell cycle regulation. Notably, βII spectrin dysfunction is associated with embryonic lethality and the DNA damage response. More recently, the detection of altered βII spectrin expression in tumors indicated that βII spectrin might be involved in the development and progression of cancer. Its mutations and disorders could result in developmental disabilities and various diseases. The versatile roles of βII spectrin in disease have been examined in an increasing number of studies; nonetheless, the exact mechanisms of βII spectrin are still poorly understood. Thus, we summarize the structural features and biological roles of βII spectrin and discuss its molecular mechanisms and functions in development, homeostasis, regeneration and differentiation. This review highlight the potential effects of βII spectrin dysfunction in cancer and other diseases, outstanding questions for the future investigation of therapeutic targets. The investigation of the regulatory mechanism of βII spectrin signal inactivation and recovery may bring hope for future therapy of related diseases.

Electrostatic polarization plays an important role in characterizing non-bonded interactions of molecule dynamics (MD) simulation of biomolecules. In this work, we extended a simple fluctuating-charge model, the effective polarizable bond (EPB) model to DNA simulations. Following the previously proposed EPB method, we re-parametrized the EPB model for DNA systems with the consideration of a realistic local electric-field environment and derived a set of DNA-specific EPB parameters. Two typical B-DNA systems, a pure DNA 1BNA and a ligand-DNA 8BNA systems were simulated respectively in the ff14SB and ff14SB(EPB) force fields. Results demonstrate that use of the EPB model in the DNA simulations can cause shrinking of DNA double strands along central axis and strengthen base-pair/ligand-DNA hydrogen-bond (HB) interactions. Furthermore, it stabilizes residue-level fluctuations for the 1BNA. However, it is largely different for these two DNA systems to mimic conformation changes of the minor/major grooves by the EPB model. Lastly, it is tested that approximately %9 similar to%9.9 CPU costs are additionally taken to execute the EPB calculations compared with the conventional ff14SB force field.

Smoking is an independent risk factor for atherosclerosis. The smoke produced by tobacco burning contains more than 7000 chemicals, among which nicotine is closely related to the occurrence and development of atherosclerosis. Nicotine, a selective cholinergic agonist, accelerates the formation of atherosclerosis by stimulating nicotinic acetylcholine receptors (nAChRs) located in neuronal and non-neuronal tissues. This review introduces the pathogenesis of atherosclerosis and the mechanisms involving nicotine and its receptors. Herein, we focus on the various roles of nicotine in atherosclerosis, such as upregulation of growth factors, inflammation, and the dysfunction of endothelial cells, vascular smooth muscle cells (VSMC) as well as macrophages. In addition, nicotine can stimulate the generation of reactive oxygen species, cause abnormal lipid metabolism, and activate immune cells leading to the onset and progression of atherosclerosis. Exosomes, are currently a research hotspot, due to their important connections with macrophages and the VSMC, and may represent a novel application into future preventive treatment to promote the prevention of smoking-related atherosclerosis. In this review, we will elaborate on the regulatory mechanism of nicotine on atherosclerosis, as well as the effects of interference with nicotine receptors and the use of exosomes to prevent atherosclerosis development.