An overview of potential cardioprotective benefits of xanthophylls in atherosclerosis:an evidence-based review

Atherosclerosis,as the most prevalent form of cardiovascular disease,is characterized by oxidized lowdensity lipoprotein(ox-LDL)accumulation in the vascular wall,increased inflammation of the large arteries,dysfunction of the endothelial cells(ECs)and vascular smooth muscle cells(VSMCs),which may eventually lead to the formation of plaques.Xanthophylls,one of the main groups of carotenoids,have been proposed as preventive agents or adjunct therapies to prevent and slow the progression of atherosclerosis due to their cardioprotective properties.However,the underlying preventive mechanism of action of xanthophylls on the pathogenesis of atherosclerosis remains unclear,and clinical evidence of the effect of xanthophylls on atherosclerosis have not yet been summarized and critically reviewed.In this regard,we conducted a comprehensive literature search in four scientific databases(Pub Med,Google Scholar,Science Direct and Web of Science)and carefully analyzed the existing evidence to provide meaningful insights on the association between xanthophylls and atherosclerosis from various aspects.Based on the evidence from in vitro and in vivo studies,we explored several potential mechanisms,including antioxidant effect,anti-inflammatory effect,regulation of lipid metabolism,and modulation of ECs and VSMCs dysfunction,and we found that a clear picture of regulatory pathways of xanthophylls on atherosclerosis prevention and treatment is still lacking.In addition,epidemiological studies suggested the possible relationship among high dietary intake of xanthophylls,high plasma/serum xanthophylls and a reduced risk of atherosclerosis.Direct evidence from interventional studies investigating the effect of xanthophylls on atherosclerosis is very sparse,whilst indirect clinical evidence was only limited to astaxanthin and lutein.Therefore,well-designed long-term randomized controlled trials(RCTs)are highly recommended for future studies to investigate the effective dose of different xanthophylls on atherosclerosis prevention and their possible ancillary effect in conjunction with drug therapies on different stages of atherosclerosis.

Top Five Stories of the Cellular Landscape and Therapies of Atherosclerosis:Current Knowledge and Future Perspectives

Atherosclerosis(AS)is characterized by impairment and apoptosis of endothelial cells,continuous systemic and focal inflammation and dysfunction of vascular smooth muscle cells,which is documented as the traditional cellular paradigm.However,the mechanisms appear much more complicated than we thought since a bulk of studies on efferocytosis,transdifferentiation and novel cell death forms such as ferroptosis,pyroptosis,and extracellular trap were reported.Discovery of novel pathological cellular landscapes provides a large number of therapeutic targets.On the other side,the unsatisfactory therapeutic effects of current treatment with lipid-lowering drugs as the cornerstone also restricts the efforts to reduce global AS burden.Stem cell-or nanoparticle-based strategies spurred a lot of attention due to the attractive therapeutic effects and minimized adverse effects.Given the complexity of pathological changes of AS,attempts to develop an almighty medicine based on single mechanisms could be theoretically challenging.In this review,the top stories in the cellular landscapes during the initiation and progression of AS and the therapies were summarized in an integrated perspective to facilitate efforts to develop a multi-targets strategy and fill the gap between mechanism research and clinical translation.The future challenges and improvements were also discussed.

Atherosclerosis originating from childhood:Specific features

Atherosclerosis is extremely widespread.Traditionally,it is considered a disease of older people,who most often experience problems with the heart and blood vessels.While much attention from the scientific community has been paid to studying the association between aging and atherosclerosis,as well as its consequences,there is evidence that atherosclerosis occurs at an early age.Atherosclerosis may form both during intrauterine development and in childhood.Nutrition plays an important role in childhood atherosclerosis,along with previous infectious diseases and excess weight of both the child and the mother.In the present review,we examined the development of atherosclerosis and the prerequisites in childhood.

Hepatocyte growth factor enhances the ability of dental pulp stem cells to ameliorate atherosclerosis in apolipoprotein E-knockout mice

BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.

Study on the Mechanism of Action of Glyasperin A in the Treatment of Atherosclerosis Based on Network Pharmacology and Molecular Docking

[Objectives] This study was conducted to investigate the mechanism of action of glyasperin A in the treatment of atherosclerosis using a network pharmacology approach. [Methods] Targets related to atherosclerosis were searched in GeneCards database. An active ingredient-disease-target network was constructed by Cytoscape 3.7.1. A target protein interaction network was constructed by String database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the DAVID database. [Results] Glyasperin A acted on 36 atherosclerosis-related targets, and the biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, barrier, and lipid oxidation, etc. The results showed that glyasperin A acted on 36 atherosclerosis-related targets. The biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, positive regulation of protein localization to nucleus, and hepoxilin biosynthetic process, and it played an anti-fatigue role through signal pathways such as serotonergic synapse, efferocytosis, arachidonic acid metabolism, chemical carcinogenesis-receptor activation and platelet activation. [Conclusions] Glyasperin A has multi-target and multi-pathway effects in the treatment of atherosclerosis. This study provides reference for further research on glyasperin A in the treatment of atherosclerosis.

Effects of ginkgo flavone aglycone on atherosclerosis based on network pharmacology,molecular docking,and in vitro experiments

Background:Ginkgo flavone aglycones(GA),a Ginkgo(Ginkgo biloba)extract,has been proven to have good biological activity in atherosclerosis(AS)treatment.Moreover,its active compounds and the corresponding mechanism for the treatment of AS remain unclear.Methods:To evaluate and identify the potential pharmacological mechanisms of GA in AS treatment,the program Cytoscape was used to generate network mappings of the GA-AS-potential target gene.GO and KEGG enrichment analyses were performed to further investigate the potential mechanism of AS and the pharmacological properties of GA.A molecular docking approach was utilized to determine the GA components that interact with Akt.In vitro experiments were carried out to identify the anti-atherosclerotic effects of GA by targeting Akt.Results:Network pharmacological research determined that the active components of GA(quercetin,kaempferol,and isorhamnetin)correlated with AS target genes such as AKT1,EGFR,SRC,ESR1,PTGS2,MMP9,KDR,GSK3B,APP,and MMP2,respectively.GO enrichment and KEGG analysis showed that PI3K-Akt signaling may play an important role in GA treatment.Molecular docking experiments indicated that quercetin,kaempferol,and isorhamnetin integrate into the binding pockets of the most potentially beneficial GA-AS target protein(Akt).Consequently,cell experiments were conducted to support the anti-atherosclerotic activity of GA on AS by inhibiting the phosphorylation of AKT1 and its downstream signaling molecules,which regulated the proliferation of HASMCs.Conclusion:Our results detailed GA's active ingredients,potential targets,and molecular basis against AS.GA may exert anti-atherosclerotic effects by suppressing Akt phosphorylation and inhibiting the proliferation of HASMCs.It also proposed a viable approach to determining the scientific foundation and therapeutic mechanism of Chinese herbal medicine extracts in disease therapy.

Effect of Chlorella Intake on the Development of Atherosclerosis and Spontaneous Thrombolytic Activity

Background and Purpose: Thrombotic disease is a leading cause of death in industrialized countries. The development of atherosclerosis is a major underlying pathogenesis. Atherosclerotic lesions are largely related to abnormalities in lipid metabolism, and improvement of dietary habits is of great significance. Chlorella is a unicellular organism belonging to the green algae family, and is consumed worldwide as a functional food for the purpose of health promotion due to its excellent nutritional balance including high quality protein. In this study, we investigated the effects of long-term consumption of Chlorella as a food on the development of atherosclerosis and its ability to dissolve thrombi caused by the disruption of the atherosclerotic layer as a functional study of Chlorella. Methods: ApoE−/− and Ldlr−/− double-knockout mice were fed a chlorella-supplemented experimental diet for 14 weeks. The Entire aorta method was used to measure atherosclerosis development, and the area of sclerotic vessels was evaluated as a percentage of the total area of vessels. In addition, mRNA levels of lipid metabolism-related proteins in the liver and blood vessels were analyzed, as well as blood lipoprotein analysis. Spontaneous thrombolytic activity was measured by measuring the change in volume over time of thrombus formed in microvessel running over the cremaster muscle of the mice using the He-Ne laser-induced thrombus model. Results: There was no significant difference between the two groups in atherosclerosis development compared to the placebo group. However, a significant decrease in SREBP-1 mRNA level and a significant increase in mRNA levels of LXR and CPY71a were observed in the chlorella group. Cholesterol and TG levels in each lipoprotein fraction did not differ between the two groups. On the other hand, thrombolysis in vivo was not significantly different between the two groups in terms of thrombus volume at 60 minutes after thrombus formation. However, a trend toward decreased PAI-1 and TAFI mRNA expression levels was observed in the chlorella group. Conclusion: Intake of chlorella as a food suggested an effect on cholesterol catabolism, increased bile acid synthesis, improved lipid metabolism, and inhibited the development of atherosclerosis. Furthermore, it was suggested that chlorella may suppress the expression of fibrinolytic inhibitory factor and enhance thrombolytic activity.

Association between Fundus Atherosclerosis and Carotid Arterial Atherosclerosis

Objective: To investigate the correlation between fundus atherosclerosis and carotid arterial atherosclerosis. Methods: A total of 516 people undergoing physical examination in Deyang People’s Hospital between June 2020 and December 2022 were randomly selected. Fundus atherosclerosis and carotid arterial atherosclerosis were evaluated by fundus photography and carotid artery ultrasonography, respectively. Results: Among the 516 physical examination patients, 198 (38.4%) had normal fundus examination, and 318 (61.6%) had fundus arteriosclerosis. Among them, 166 cases were of grade I (32.2%), 86 cases were of grade II (16.7%), and 66 cases were of grade III (12.8%). There were 286 cases (55.4%) without carotid atherosclerosis, 201 cases (38.9%) with carotid atherosclerotic plaque, and 33 cases (6.4%) with carotid stenosis. Fundus arteriosclerosis is independently associated with carotid artery intima-media thickness, vulnerable plaques, plaque scores, and carotid artery stenosis (P Conclusion: In summary, there is a close relationship between carotid artery disease and the degree of arteriosclerosis in the eyeground. Fundus photography is a simple, non-invasive, and easily acceptable method of inspection. The results obtained from it are useful in determining the severity of carotid atherosclerosis and guiding early detection and intervention in clinical cases. This can help reduce the incidence of cardiovascular and cerebrovascular diseases.

Calpain-1 Mediated Mitochondria ROS/NLRP3 Inflammasome in Atherosclerosis

Calpains are calcium-activated cysteine proteases. There are two main isoforms of calpain that are ubiquitously expressed in tissues, calpain μ or calpain 1, which requires micromolar Ca2+ for activation, and calpain or 2, which requires millimolar Ca2+ for activation. The presence of other calpains is tissue specific. Atherosclerosis (AS) is an important risk factor for cerebral infarction, coronary heart disease and peripheral vascular disease. It was originally thought that AS was caused by impaired lipid metabolism. This research briefly reviewed Calpain Family, the structure and activation mechanism of calpain1, Calpains in the pathogenesis of atherosclerosis, NLRP3 structural characteristics and activation, ROS/NLRP3 inflammasome activation mechanism and ROS/NLRP3 inflammasome in atherosclerosis. The research showed that the Calpain-1 may play an important role in mitochondrial ROS/NLRP3 inflammasome in atherosclerosis.

Research progress on the influence of local hemodynamics on carotid atherosclerosis

The reasons for the formation of atherosclerosis are diverse and complex,and atherosclerosis as a kind of systemic disease has the characteristics of focal selectivity,which occurs in the carotid bifurcation.The feature enables a large number of studies have found that the severe local hemodynamic characteristics has a great influence to the occurrence of this disease.This paper briefly reviews the related research on the local hemodynamics of carotid bifurcation.The relevant parameters of local hemodynamics were sorted out and summarized,and the effects of wall shear force and its derived parameters on the generation,progression and rupture of carotid atherosclerosis and their clinical applications were reviewed,in order to provide mechanical information for the early warning of carotid plaque rupture.At the same time,this paper describes the transformation of local hemodynamics research in the clinical application of carotid atherosclerosis disease,in order to provide personalized selection and basis for the clinical treatment of this disease.

Overexpressed PKM2 promotes macrophage phagocytosis and atherosclerosis

Background:The expression of pyruvate kinase muscle 2(PKM2)is augmented in macrophages of patients with atherosclerotic coronary artery disease.The role of PKM2 in atherosclerosis is to be determined.Methods:Global and myeloid cell-specific PKM2 knock-in mice with ApoE^(-/-)background(ApoE^(-/-),PKM2^(KI/KI)and Lyz2-cre,ApoE^(-/-),and PKM2^(flox/flox))were produced to evaluate the clinical significance of PKM2 in atherosclerosis development.Wild-type and PKM2 knock-in macrophages were isolated to assess the function of PKM2 in macrophage phagocytosis.Atherosclerotic mice were treated with PKM2 inhibitor shikonin(SKN)to evaluate the therapeutic potential of PKM2 suppression in atherosclerosis.Results:Oxidized low-density lipoprotein(oxLDL)upregulated PKM2 in macrophages.PKM2 in return promoted the uptake of oxLDL by macrophages.Overexpressed PKM2 accelerated atherosclerosis in mice.SKN blocked the progress of mouse atherosclerosis.Conclusions:PKM2 accelerates macrophage phagocytosis and atherosclerosis.Targeting PKM2 is a potential therapy for atherosclerosis.

Cardiac Computed Tomography for the Diagnosis of Coronary Artery Atherosclerosis

Coronary artery disease (CAD) is a leading cause of mortality and morbidity in developed countries, although percutaneous coronary intervention and coronary artery bypass grafting have developed recently. Appropriate diagnosis will improve the prevention, treatment, and care of all patients. We could diagnose only calcification in the coronary arteries with the past computed tomography. Recently, multislice computed tomography has been already accepted as an efficient non-invasive tool for the detection of coronary artery stenosis. We get to estimate the coronary artery stenosis with cardiac computed tomography. We discuss the usefulness of cardiac computed tomography for the risk stratification of coronary artery atherosclerosis.

Diffuse arterial atherosclerosis presenting with acute ischemic gastritis: A case report

BACKGROUND Ischemic gastritis is a clinically rare disease with high mortality that infrequently reported in the medical literature and under-recognized clinically and histopatho-logically.Early diagnosis and treatment can only be achieved through upper gastrointestinal endoscopy after symptoms appear.CASE SUMMARY A 68-year-old woman with a history of intracranial aneurysm developed dizziness,chest tightness and unconsciousness for 2 d.Computed tomography angiography showed diffuse coronary atherosclerosis,moderate to severe stenosis in the proximal end of the left anterior descending branch,multiple calcified plaques in the proximal end of the circumflex branch and right coronary artery,and mild to moderate stenosis.The patient also developed diffuse atherosclerosis in the splenic and mesenteric arteries,with mild lumen stenosis and athero-sclerosis in the abdominal aorta and its branches.Endoscopy showed submucosal congestion and damage of the entire gastric mucosa,of which the fundus and body of the stomach were most seriously affected.The mucosa was swollen,with a deep purple color,surface erosion and dark red oozing blood.Pathological examination showed bleeding and necrosis of the gastric mucosa,with residual contours of the gastric glands,consistent with ischemic gastritis.CONCLUSION Ischemic gastritis is a rare disease that may be difficult to diagnose as its symptoms may be similar to those of other gastrointestinal diseases.Diagnosis is usually based on endoscopic and pathological examinations,which show insufficient blood supply to the gastric mucosa leading to mucosal damage and necrosis.

Isoliquiritigenin regulated ox-LDL through activating the PPAR-γ signaling pathway to stabilize atherosclerosis plaques

Objective:To explore the molecular mechanisms of isoliquiritigenin in stabilizing atherosclerotic plaques by activating PPAR-γsignal pathway to regulate ox-LDL metabolism.Methods:The ApoE-/-mice AS carotid plaque model was prepared by using high fat diet and right perivascular carotid collar placement(PCCP).ApoE-/-mice were randomly divided into the model group and the isoliquiritigenin group after PCCP.C57BL/6J mice were used for the control group.High fat diet continued feeding for 8 weeks after PCCP to establish the AS model.Automatic biochemical analyzer was used to test levels of total cholesterol(TC),triacylglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C).ELISA was used to measure oxidized low-density lipoprotein(ox-LDL)in serum.Hematoxylin-eosin(HE)staining was used to observe the pathological pattern of the carotid artery,and then calculated the carotid parameters.Oil red O staining was used for lipid determination,Masson staining was used to determine collagen content,MOMA-2 andα-SMA immunohistochemical staining were used to determine macrophages and smooth muscle cells,and to calculate the vulnerability index.Western blot was used to detected the expression of PPAR-γ,LXR-α,FABP-4,MMP-2 and MMP-9 in mice arteries.Results:Compared with the normal group,TC、TG、LDL-C、HDL-C and ox-LDL were increased in the model group.Compared with the model group,TC、TG、LDL-C and ox-LDL were reduced,and there was no significant change in HDL-C of the isoliquiritigenin group.Compared with the normal group,intima thickness(IT),intima/media thickness(IT/MT),plaque area(PA),and plaque area/lumen area(PA/LA)of carotid arteries were increased,the content of lipid and MOMA-2 in plaques was increased,collagen andα-SMA content decreased,and the vulnerability index was higher in the model group.The expression of PPAR-γand LXR-αwere reduced and the expression of FABP-4,MMP-2 and MMP-9 were increased in the model group.Compared with the model group,carotid IT,IT/MT,PA,and PA/LA were reduced,the content of lipid and MOMA-2 in plaques was decreased,collagen andα-SMA content were increased,and the vulnerability index was decreased in the isoliquiritigenin group.PPAR-γand LXR-αexpression were increased,FABP-4,MMP-2 and MMP-9 expression were decreased significantly in the isoliquiritigenin group.Conclusion:Isoliquiritigenin can exert anti-AS effects by activating PPAR-γ,up-regulating LXR-α,reducing FABP-4 expression,reducing ox-LDL,reducing the protein expression of MMP-2 and MMP-9,decreasing plaque vulnerability index,and increasing plaque stability.

Enhanced Detection of Cerebral Atherosclerosis Using Hybrid Algorithm of Image Segmentation

In medical science for envisaging human body’s phenomenal structure a major part has been driven by image processing techniques.Major objective of this work is to detect of cerebral atherosclerosis for image segmentation applica-tion.Detection of some abnormal structures in human body has become a difficult task to complete with some simple images.For expounding and distinguishing neural architecture of human brain in an effective manner,MRI(Magnetic Reso-nance Imaging)is one of the most suitable and significant technique.Here we work on detection of Cerebral Atherosclerosis from MRI images of patients.Cer-ebral Atherosclerosis is a cerebral vascular disease causes narrowing of the arteries due to buildup of fatty plaque inside the blood vessels of the brain.It leads to Ischemic stroke if not diagnosed early.Stroke affects majorly old age people and percentage of affected women is more compared to men.Results:Preproces-sing is done by using alpha trimmed meanfilter which is used to remove noise and also it enhances the image.Segmentation of cerebral atherosclerosis is done by using K-means clustering,Contextual clustering,and proposed Hybrid algo-rithm.Various parameters like Correlation,Pixel density,energy is determined and from the analysis of parameters it is determined that proposed Hybrid algo-rithm is efficient.

Leg Atherosclerosis in Japanese COPD Patients: Prevalence of Undiagnosed Peripheral Artery Disease and Association between Leg Atherosclerosis and Clinical Indices

Introduction: Several studies have suggested that decreased FEV1 is associated with cardiovascular risk in COPD patients. Objective: To identify the prevalence of undiagnosed peripheral artery disease (PAD) and the relationship between leg atherosclerosis and clinical indices, which predict COPD mortality in Japanese COPD patients. Methods: We performed a cross-sectional study in 51 COPD patients and 51 age-matched, healthy control smokers. We measured ankle-brachial index (ABI) as a marker of atherosclerosis of the legs, pulmonary function, body mass index, modified Medical Research Council (MMRC) dyspnea scale, and smoking pack-years. We also calculated the ADO index (Age, Dyspnea, and Obstruction), an established predictor of mortality in COPD patients. Co-morbidities including diabetes mellitus, hypertension, and hypercholesterolemia were identified from blood laboratory tests and medical records. Results: Five subjects (9.8%) had an ABI 0.9. ABI was significantly lower in the COPD patients than in the healthy control smokers (p 0.05). The prevalence of PAD was marginally higher in COPD patients than in control smokers (p = 0.09), with the prevalence of ABI 1.0 being significantly higher in COPD patients than in control smokers (p = 0.04). In the COPD patients, ABI showed significant correlations with age (p = 0.006), FEV1 (p = 0.004), smoking pack-years (p = 0.047), MMRC dyspnea scale (p = 0.0005), SaO2 (p = 0.001), andADOindex (p 0.001). Multiple linear regression modeling showed the factors associated independently with ABI were age, FEV1, smoking pack-years, MMRC dyspnea scale, and SaO2. Conclusion: The risk of leg atherosclerosis in Japanese COPD patients is higher than in smokers without COPD. Leg atherosclerosis in COPD patients is associated with clinical indices that predict COPD mortality.

Exploration on the mechanism of Radix Astragali-Caulis Spatholobi by Qi-invigorating and blood-activating combination for the treatment of atherosclerosis based on network pharmacology

The objective of this study was to investigate the main active ingredients,potential targets,and possible mechanisms of action of the combination of Radix Astragali and Caulis Spatholobi for the treatment of atherosclerosis using network pharmacology.The study aimed to provide a reference basis for the development of new formulations and clinical use of Chinese medicine.The main components of Radix Astragali and Caulis Spatholobi were obtained from the TCMSP,BATMAN-TCM database,and literature reports.The targets corresponding to the main components were imported into the Uniprot database to standardize the names,and target information was supplemented with the Swiss Target Prediction database.Disease-related targets were obtained from DrugBank,OMIM,CTD,GeneCards,and DisGeNET online databases.Venn tools were used to obtain the potential targets of Radix Astragali and Caulis Spatholobi for the treatment of AS.The intersecting genes were imported into the STRING 11.5 database to construct protein-protein interaction network maps and analyze their interactions.Cytoscape 3.7.1 software was used to mine their core targets.GO function and KEGG signaling pathway enrichment analysis were performed using the DAVID v2023q1 database.The results were imported into the“Bioinformatics Cloud Platform”to generate enrichment bubble maps.Finally,the“component-target-pathway”diagram was constructed using Cytoscape 3.7.1 software.The study found that 78 major active ingredients and 527 potential targets were obtained from Radix Astragali and Caulis Spatholobi.The main active components of the two in combination for the treatment of AS are quercetin,stigmasterol,kaempferol,luteolin,formononetin,etc.The key targets involve CDKN1A,E2F1,CDK4,CDK2,CDK1,RB1,TP53,CDKN1B,IL6,JUN,etc.The main pathways involved the AGE-RAGE signaling pathway in diabetic complications,cancer pathway,etc.The biological processes involved include positive regulation of gene expression,negative regulation of apoptotic process,etc.The study initially verified the feasibility of the combination of Radix Astragali-Caulis Spatholobi by Qi-invigorating(promoting human metabolic activity)and blood-activating for the treatment of AS.It demonstrated that the combination of Chinese medicine has multi-level,multi-target,and multi-pathway mechanisms of action to treat the disease,providing a reference basis for the development and utilization of new drugs.

Mechanism of Cordyceps sinensis in atherosclerosis treatment based on network pharmacology and molecular docking analysis

Background:The present study intented to delve into the molecular mechanism of Cordyceps sinensis(C.sinensis)in treating atherosclerosis by combining network pharmacology and molecular docking analysis.Methods:We searched the databases including Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,PubChem,and PharmMapper to screen out the active chemical ingredients of C.sinensis and the corresponding targets.The String database was used for the matching normalization of results,and the software Cytoscape 3.7.2 was adopted to establish the C.sinensis-active components-targets of action-disease network.The databases of Online Mendelian Inheritance in Man database,GeneCards,Therapeutic Target Database,and DisGNET were searched to yield the major targets of atherosclerosis(AS),which were matched with the active component targets of C.sinensis to identify the potential therapeutic targets.The String database was utilized to set up the protein-protein interaction network,and Cytoscape software was applied for topological analysis,which was followed by the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes signaling pathway analysis based on the DAVID database.Finally,the core components of C.sinensis and the targets of action were confirmed via molecular docking on AutoDock Vina and PyMOL.Results:In total,7 bioactive ingredients of C.sinensis were identified from Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform database and 319 predicted targets were obtained,231 of which were associated with AS.The core targets involved in AS treatment with C.sinensis included MAPK1,SRC,PIK3R1,AKT1,and HSP90AA1.The enrichment analysis unveiled the primary pathways involved in these processes,such as pathways in cancer and lipid and atherosclerosis.Moreover,through molecular docking,it was found that the active ingredients of C.sinensis presented with strong binding capacities with their corresponding targets,and the strongest binding capacity was observed between peroxyergosterol and SRC.Conclusions:The present study revealed at the molecular level that C.sinensis played its role in AS treatment through multiple drug active components,targets of action and pathways,which would point out the direction and provide theoretic basis for future research.

To explore the mechanism of Naodesheng tablets in the treatment of atherosclerosis based on network pharmacology and bioinformatics

Background:Naodesheng tablets(NDST)was widely used in clinical treatment as a drug for cardiovascular diseases,but the mechanism for treating atherosclerosis was unknown.On the basis of network pharmacology and bioinformatics,predict the relevant targets and signalling pathways for NDST in the treatment of atherosclerosis.Methods:First,the targets of NDST and the targets for treating atherosclerosis were looked for in different databases.Next,Venny 2.1.0 was used to find the genes that overlapped between NDST and targets for treating atherosclerosis.Subsequently,the herb-active ingredient-target-disease were obtained to explore the hub compound.Furthermore,the Metascape database was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis.And we constructed the“active ingredient-intersection target-pathway”network by Cytoscape software to gain the hub genes and pathways.Finally,molecular docking was used to verify the affinity of hub ingredients and hub genes.Results:In the results,67 active ingredients and 322 targets of NDST were selected in ingredients-targets network.154 overlapping targets of NDST(322)and atherosclerosis(1330)were obtained.Then,the herb-active ingredient-target-disease showed that quercetin,apigenin and luteolin were the hub ingredients to treat atherosclerosis.Further,the hub genes(PTGS2,RXRA,CASP3)and pathways(lipid and atherosclerosis)were accessed in active ingredient-intersection target-pathway.Finally,the results indicated that quercetin,apigenin and luteolin were better binding the PTGS2,RXRA,CASP3,especially PTGS2 and luteolin in molecular docking.Conclusion:In conclusion,quercetin,apigenin and luteolin,as the main ingredients of NDST could play a important role in PTGS2,RXRA,and CASP3 for treating atherosclerosis via the lipid and atherosclerosis(TNF signaling pathway).

Metaheuristics with Deep Learning Empowered Biomedical Atherosclerosis Disease Diagnosis and Classification

Atherosclerosis diagnosis is an inarticulate and complicated cognitive process.Researches on medical diagnosis necessitate maximum accuracy and performance to make optimal clinical decisions.Since the medical diagnostic outcomes need to be prompt and accurate,the recently developed artificial intelligence(AI)and deep learning(DL)models have received considerable attention among research communities.This study develops a novel Metaheuristics with Deep Learning Empowered Biomedical Atherosclerosis Disease Diagnosis and Classification(MDL-BADDC)model.The proposed MDL-BADDC technique encompasses several stages of operations such as pre-processing,feature selection,classification,and parameter tuning.Besides,the proposed MDL-BADDC technique designs a novel Quasi-Oppositional Barnacles Mating Optimizer(QOBMO)based feature selection technique.Moreover,the deep stacked autoencoder(DSAE)based classification model is designed for the detection and classification of atherosclerosis disease.Furthermore,the krill herd algorithm(KHA)based parameter tuning technique is applied to properly adjust the parameter values.In order to showcase the enhanced classification performance of the MDL-BADDC technique,a wide range of simulations take place on three benchmarks biomedical datasets.The comparative result analysis reported the better performance of the MDL-BADDC technique over the compared methods.