Model informed precision medicine of Chinese herbal medicines formulas-A multi-scale mechanistic intelligent model.

Recent trends suggest that Chinese herbal medicine formulas (CHM formulas) are promising treatments for complex diseases. To characterize the precise syndromes, precise diseases and precise targets of the precise targets between complex diseases and CHM formulas, we developed an artificial intelligence-based quantitative predictive algorithm (DeepTCM). DeepTCM has gone through multilevel model calibration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling, molecular and theoretical levels of traditional Chinese medicine (TCM). As an example, our model simulated the optimal CHM formulas for the treatment of coronary heart disease (CHD) with depression, and through model sensitivity analysis, we calculated the balanced scoring of the formulas. Furthermore, we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions. Finally, we experimentally confirmed the therapeutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice. This novel multiscale model opened up a new avenue to combine "disease syndrome" and "macro micro" system modeling to facilitate translational research in CHM formulas.

Mediterranean diet for cardiovascular disease: an evidence mapping study.

OBJECTIVE: This study aimed to evaluate the methodological quality of existing meta-analyses (MA) and the quality of evidence for outcome indicators to provide an updated overview of the evidence concerning the therapeutic efficacy of the Mediterranean diet (MD) for various types of CVD. DESIGN: We conducted comprehensive searches of PubMed, Cochrane Library, and Embase databases. The quality of the MA was assessed using the A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) checklist, while the Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence evaluation system was employed to evaluate the quality of evidence for significant outcomes. SETTING: The CVD remains a significant contributor to global mortality. Multiple MA have consistently demonstrated the efficacy of medical interventions in managing CVD. However, due to variations in the scope, quality and outcomes of these reviews, definitive conclusions are yet to be established. PARTICIPANTS: This study included five randomized trials and twelve non-randomized studies, with a combined participant population of 716 318. RESULTS: The AMSTAR 2 checklist revealed that 54·55 % of the studies demonstrated high quality, while 9·09 % exhibited low quality, and 36·36 % were deemed critically low quality. Additionally, there was moderate evidence supporting a positive correlation between MD and CHD/acute myocardial infarction, stroke, heart failure, cardiovascular events, coronary events and major adverse cardiovascular events. CONCLUSIONS: This study indicates that although recognizing the potential efficacy of MD in managing CVD, the quality of the methodology and the evidence for the outcome indicators remain unsatisfactory.

Photoacoustic Spectroscopy Gas Detection Technology Research Progress.

Photoacoustic spectroscopy (PAS) can be utilized as an ultrasensitive gas detection method. The basic principles of gas detection using PAS are discussed in this paper. First, the basic instrumentation for a PAS gas detection system is introduced focusing on the photoacoustic cell. The discussion includes non-resonant photoacoustic cells and the different types of resonant photoacoustic cells, including the longitudinal photoacoustic cell, the Helmholtz photoacoustic cell, the T-type photoacoustic cell, and the high-frequency resonant photoacoustic cell. The basic working principles of each of these, cells as well as the advantages and disadvantages of photoacoustic cells are discussed, and the development of newer types of photoacoustic cells in recent years is outlined in detail. This review provides detailed reference information and guidance for interested researchers who would like to design and build advanced photoacoustic cells for gas detection.

Efficacy of cupping therapy on pain outcomes: an evidence-mapping study.

Objective: Cupping therapy is an ancient technique of healing used to treat a variety of ailments. An evidence-mapping study was conducted to summarize the existing evidence of cupping therapy for pain-related outcomes and indicate the effect and the quality of evidence to provide a comprehensive view of what is known. Methods: PubMed, Cochrane Library, Embase, and Web of Science were searched to collect the meta-analyses investigating the association between cupping therapy and pain-related outcomes. The methodological quality was assessed by using the AMSTAR 2 tool. Significant outcomes (p < 0.05) were assessed using the GRADE system. The summary of evidence is presented by bubble plots and human evidence mapping. Results: Fourteen meta-analyses covering five distinct pain-related conditions were identified and assessed for methodological quality using the AMSTAR 2, which categorized the quality as critically low (36%), low (50.0%), moderate (7%), and high (7%). In accordance with the GRADE system, no high-quality evidence was found that demonstrates the efficacy of cupping therapy for pain-related outcomes. Specifically, for neck pain, there were two moderate-quality, four low-quality, and two very low-quality evidence, while only one very low-quality evidence supports its efficacy in treating herpes zoster and one low-quality evidence for chronic back pain. Additionally, for low back pain, there were two moderate-quality, one low-quality, and four very low-quality evidence, and for knee osteoarthritis, three moderate-quality evidence suggest that cupping therapy may alleviate pain score. Conclusion: The available evidence of very low-to-moderate quality suggests that cupping therapy is effective in managing chronic pain, knee osteoarthritis, low back pain, neck pain, chronic back pain, and herpes zoster. Moreover, it represents a promising, safe, and effective non-pharmacological therapy that warrants wider application and promotion.Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021255879, identifier: CRD42021255879.

Global research trends in atherosclerosis-related NF-κB: a bibliometric analysis from 2000 to 2021 and suggestions for future research.

Background: Atherosclerosis (AS) is closely related to stroke and cardiovascular diseases. Nuclear factor kappa-B (NF-κB) is the master regulator of inflammation, and thus, modulating the transcription of NF-κB can improve AS. Methods: In this study, we conducted a bibliometric analysis to identify the frontiers, hotspots, and features of global research output on NF-κB in AS from 2000 to 2021. Papers published from 2000 to 2021 and the recorded information were retrieved from the Science Citation Index-Expanded of the Web of Science Core Collection. Bibliometric analysis and visualization were performed using VOSviewer and CiteSpace, including an analysis of the general distribution of annual output, highly productive countries, active journals, active institutions and authors, keywords, and co-cited references. Results: A total of 5,439 original articles and reviews were retrieved and analyzed, and the results indicated that the annual number of publications on NF-κB in AS has been increasing in waves over the past 22 years. The majority of papers were published in China, while the USA had the highest number of citations and H-index. The most productive affiliation and journal were the University of California System and Arteriosclerosis Thrombosis and Vascular Biology, respectively. The papers of Chiu JJ. received the highest number of citations globally in 2011. The keywords, "nlrp3 inflammasome" and "microRNA", have recently attracted considerable attention, and very frequently occurring keywords included "NF kappa B", "atherosclerosis", "expression", "activation", "endogenous cell", and "oxidative stress". New keywords in 2021 included "muscle", "attenuates atherosclerosis", "mesenchymal transition", "metabolic disorder", and "palmitic acid". Conclusions: AS and inflammation have become research hotspots lately. Over the past decade, most studies have focused on basic research, and pathways associated with the regulatory role of NF-κB in AS have become a particular focus in recent studies. Moreover, our study revealed that NF-κB plays a remarkable role in AS and may be a therapeutic target.

Low Dimensional Nanostructure-Assisted Long-Range Surface Plasmon Resonance Sensors With High Figure of Merit.

Long-range surface plasmon resonance (LRSPR) sensors have been extensively studied by virtue of their extremely narrow full width at half maxima (FWHM) characteristics, but their low sensitivity remains an important factor limiting the figure of merit (FOM), making the sensors have difficulties in detecting small refractive index changes accurately. To address this problem, this paper proposes and demonstrates a low dimensional nanostructure (Au nanospheres, WS2) assisted LRSPR sensor to achieve an effective enhancement of the sensor interfaced electric field and thus improve the sensitivity. The performance parameters of the two sensors are compared with the LRSPR sensor by finite element method analysis, and the results showed that the assistance of the low dimensional nanostructure has a positive effect on the sensor. The first refractive index sensing experiment of the WS2-assisted LRSPR sensor was realized with a 25.47% increase in sensitivity and a 7.13% increase in FOM simultaneously, and the Au nanospheres-assisted LRSPR sensor with a 29.23% increase in sensitivity and a 15.95% increase in FOM simultaneously. The introduction of low dimensional nanostructures provides a flexible and effective means of sensitization for LRSPR sensors, making the plasmon resonance sensors combine high sensitivity, narrow FWHM and high FOM, which have promising applications in biochemical sensing.

The Mitochondrial Unfolded Protein Response: A Novel Protective Pathway Targeting Cardiomyocytes.

Mitochondrial protein homeostasis in cardiomyocyte injury determines not only the normal operation of mitochondrial function but also the fate of mitochondria in cardiomyocytes. Studies of mitochondrial protein homeostasis have become an integral part of cardiovascular disease research. Modulation of the mitochondrial unfolded protein response (UPRmt), a protective factor for cardiomyocyte mitochondria, may in the future become an important treatment strategy for myocardial protection in cardiovascular disease. However, because of insufficient understanding of the UPRmt and inadequate elucidation of relevant mechanisms, few therapeutic drugs targeting the UPRmt have been developed. The UPRmt maintains a series of chaperone proteins and proteases and is activated when misfolded proteins accumulate in the mitochondria. Mitochondrial injury leads to metabolic dysfunction in cardiomyocytes. This paper reviews the relationship of the UPRmt and mitochondrial quality monitoring with cardiomyocyte protection. This review mainly introduces the regulatory mechanisms of the UPRmt elucidated in recent years and the relationship between the UPRmt and mitophagy, mitochondrial fusion/fission, mitochondrial biosynthesis, and mitochondrial energy metabolism homeostasis in order to generate new ideas for the study of the mitochondrial protein homeostasis mechanisms as well as to provide a reference for the targeted drug treatment of imbalances in mitochondrial protein homeostasis following cardiomyocyte injury.

Integrated meta-analysis, data mining, and animal experiments to investigate the efficacy and potential pharmacological mechanism of a TCM tonic prescription, Jianpi Tongmai formula, in depression.

BACKGROUND: Depression is a common psychiatric disorder and has become a growing public health issue. Traditional Chinese medicine (TCM) tonic prescriptions have been clinically proven to be an effective treatment for depression. PURPOSE: This study aimed to identify the core prescription to improve depression among the numerous TCM tonic prescriptions. METHODS AND RESULTS: First, we used meta-analysis to clarify the efficacy and safety of tonic prescriptions in depression among 37 studies and identified 16 effective tonic prescriptions. Second, we conducted data mining to analyze the tonic prescriptions and identified important nourishing herbs. Third, based on the data mining results, we constructed a Delphi experiment to investigate the effects of these important nourishing herbs in depression. Combining the results of Delphi expert questionnaires and weight analysis, a core TCM tonic prescription, Jianpi Tongmai formula (JPTMF) for the treatment of depression, was constructed and was composed of invigorating Spleen qi herbs. Fourth, we verified that JPTMF can improve chronic unpredictable mild stress (CUMS) induced depression-like behaviors in mice. Fifth, we predicted that the mechanism of JPTMF in the treatment of depression was mainly associated with chemical synaptic transmission and neuroinflammation through network pharmacology and determined preliminary confirmation through animal experiments. CONCLUSION: This study was undertaken to evaluate the efficacy of TCM tonic prescriptions on depression and construct a core TCM tonic prescription, JPTMF, through a progressive analysis. Network pharmacology and animal experiments verified the reliability of JPTMF. The proposal of JPTMF is of innovative significance, and may provide far-reaching implications for improving depression by using nourishing herbs. Furthermore, the integrated methods applied in this study provide an innovative paradigm for the standardization and scientific basis of TCM research.

Anshen Dingzhi prescription in the treatment of PTSD in mice: Investigation of the underlying mechanism from the perspective of hippocampal synaptic function.

BACKGROUND: Anshen Dingzhi prescription (ADP) is an important prescription for the treatment of mental diseases in traditional Chinese medicine and is widely used to treat neuropsychiatric disorders. PURPOSE: To explore the ameliorative effect of ADP on post-traumatic stress disorder (PTSD)-like behaviors in mice and determine the underlying mechanism. METHODS: The constituents of ADP were analyzed by UPLC-Q-TOF/MS. The PTSD-like behaviors of mice subjected to single prolonged stress (SPS) were evaluated using behavioral tests. Potential pathological changes in the hippocampus were assessed by hematoxylin and eosin (H&E) staining. Western blotting and immunohistochemistry (IHC) were employed to detect the expression of proteins involved in relevant signaling pathways. RESULTS: Five quality control markers (ginsenoside Rg1, ginsenoside Rb1, tenuifolin, poricoic acid B, and α-asarone) were detected in the ADP solution. The ginsenoside Rg1 content in ADP was found to be 0.114 mg/g. Mice subjected to SPS showed obvious fear generalization and anxiety-like behaviors. ADP treatment prevented the behavioral changes caused by exposure to SPS. Compared with control animals, the number of normal pyramidal cells in the hippocampal CA1 region of mice exposed to SPS was decreased and the number of degenerating pyramidal cells was increased; however, ADP administration could counteract these effects. Furthermore, the protein expression of BDNF, p-TrkB, µ-calpain, PSD95, GluN2A, GluA1, p-AKT, p-mTOR, and ARC was decreased, while that of PTEN and GluN2B was increased in the hippocampus of mice subjected to SPS compared with that in control animals; however, these changes in protein expression were reversed following ADP treatment. Importantly, the ameliorative effect of ADP on PTSD-like behaviors and synaptic protein expression were inhibited by rapamycin administration. CONCLUSIONS: ADP administration improves PTSD-like behaviors in mice and this effect may be mediated through an mTOR-dependent improvement in synaptic function in the hippocampus.

Research advances on surface plasmon resonance biosensors.

The surface plasmon resonance (SPR) phenomenon is of wide interest due to its sensitivity to changes in surface refractive index for the label-free, highly sensitive and rapid detection of biomarkers. This paper reviews research progress on SPR biosensors modified with different substrate structures and surface materials, surface plasmon resonance imaging (SPRI), and SPR-enhanced electrochemiluminescent (ECL) biosensors for applications in biosensing in the last five years. This paper focuses on the research on the application of the SPR phenomenon in the field of bio-detection, reviews the sensing characteristics of SPR biosensors with substrate structures of prisms, gratings, and optical fibers, and summarizes and analyzes the sensitivity and interference resistance of SPR sensors with surface modification of different materials (high-refractive index dielectric films, metallic micro- and nanostructures, and surface antifouling materials). Considering that imaging is an important tool for biomedical detection, this paper reviews the research progress on SPRI technology in the field of biomedical detection. In addition, this paper also reviews the research progress on SPR-enhanced ECL biosensors in the field of biosensing. Finally, this paper provides an outlook on the development trends of biosensing technology in terms of portable high-precision SPR sensors, reduction of self-loss of thin film materials, optimization of image processing techniques and simplification of electrode modification for ECL sensors.

Astrocytic Kir4.1 regulates NMDAR/calpain signaling axis in lipopolysaccharide-induced depression-like behaviors in mice.

The activation of Nod-like receptor protein 3 (NLRP3) inflammasome propagates pro-inflammatory signaling cascades linking to depression-like behaviors. However, the signaling pathway contributing to NLRP3 inflammasome activation and depression-like behaviors is still not clear. In this study, we evidenced that lipopolysaccharide (LPS) injection (i.p.) triggered depression-like behaviors, promoted the expression of Kir4.1, p-GluN2B and calpain-1, and activated NLRP3 inflammasome. The blockage of N-methyl-d-aspartate receptors (NMDAR) by memantine reduced LPS-induced depression-like behaviors, NLRP3 inflammasome and astrocyte activation, and calpain-1 expression. Additionally, memantine also inhibited LPS-induced reduction of postsynaptic density protein 95 (PSD-95) and Arc expression. Specific reduction of Kir4.1 in astrocytes attenuated LPS-induced expression of NLRP3 and calpain-1, and phosphorylation of GluN2B. Interestingly, LPS-induced expression of calpain-1 largely co-localized with GFAP, indicating the specific function of calpain-1 in astrocytes. Together, these data indicate that astrocytic Kir4.1 could regulate NMDAR/calpain-1 signaling axis, contributing to depression-like behaviors, likely through regulating NLRP3 inflammasome activation.

Cytochrome P450 2A6 is associated with macrophage polarization and is a potential biomarker for hepatocellular carcinoma.

Cytochrome P450 2A6 (CYP2A6) is an important metabolic enzyme and is involved in the progression of hepatocellular carcinoma (HCC). However, its specific function and the mechanism of modulation remain to be elucidated. In this study, we found that CYP2A6 is dramatically downregulated in HCC. CYP2A6 expression is closely associated with pathological grading, histologic grade, hepatitis, vascular metastasis, liver inflammation, and worse prognosis. Reduced expression of CYP2A6 contributes to alternative activation of macrophage polarization and impairs macrophage maturation and phagocytosis. Mechanistically, CYP2A6 participates in arachidonic acid metabolism, initiates 20-hydroxyeicosatetraenoic acid (HETE) generation, and inhibits epoxyeicosatrienoic acid (EET) generation. Disruption of the equilibrium between 20-HETE and EETs can induce macrophage polarization, thereby modulating antitumor immunity.

Ginsenoside Rg1 Prevents PTSD-Like Behaviors in Mice Through Promoting Synaptic Proteins, Reducing Kir4.1 and TNF-α in the Hippocampus.

Ginsenoside Rg1 is efficient to prevent or treat mental disorders. However, the mechanisms underlying the effects of ginsenoside Rg1 on post-traumatic stress disorder (PTSD) are still not known. In this study, single-prolonged stress (SPS) regime, as well as injection of lipopolysaccharide (LPS), was used to produce PTSD-like behaviors in C57 mice, and the effects of ginsenoside Rg1 (10, 20, 40 mg/kg/d, ip, for 14 days) on PTSD-like behaviors were evaluated. Our results showed that ginsenoside Rg1 promoted fear extinction and prevented depression-like behaviors in both LPS and SPS models. Importantly, ginsenoside Rg1 alleviated LPS- or SPS-stimulated expression of pro-inflammatory cytokines (IL-1ß and TNF-α), activation of astrocytes and microglia, and reduction of hippocampal synaptic proteins (PSD95, Arc, and GluA1). Ginsenoside Rg1 also reduced the increase of hippocampal Kir4.1 and GluN2A induced by PTSD regime. Importantly, reducing hippocampal astroglial Kir4.1 expression promoted fear extinction and improved depression-like behaviors in LPS-treated mice. Additionally, intracerebroventricular injection of TNF-α caused an impairment of fear extinction and promoted Kir4.1 expression in the hippocampus. Together, our study reveals novel protective effects of ginsenoside Rg1 against PTSD-like behaviors in mice, likely via promoting synaptic proteins, reducing Kir4.1 and TNF-α in the hippocampus.

The Regulation of Exosome-Derived miRNA on Heterogeneity of Macrophages in Atherosclerotic Plaques.

Exosomes are nanosized vesicles secreted by most cells, which can deliver a variety of functional lipids, proteins, and RNAs into the target cells to participate in complex intercellular communications. Cells respond to certain physical, chemical, and biological stimuli by releasing exosomes. Exosomes are rich in small molecules of RNA, including miRNAs and mRNAs, which have been demonstrated to have certain functions in recipient cells. Recent studies on single-cell RNA sequences have revealed the transcription and the heterogeneity of macrophages in Ldlr-/-mice fed with a high-fat diet. Five macrophage populations were found in the atherosclerotic plaques. It is worth noting that these subset populations of macrophages seem to be endowed with different functions in lipid metabolism and catabolism. A total of 100 differentially expressed mRNAs were selected for these subset populations. Importantly, these macrophage populations were also present in human advanced atherosclerosis. To clarify the specific functions and the regulatory mechanism of these macrophage populations, we extracted exosome RNAs from the plasma of patients with chronic coronary artery disease (CAD) and performed RNA sequencing analysis. Compared with the healthy control, a total of 14 miRNAs were significantly expressed in these patients. A total of 5,248 potential mRNAs were predicted by the bioinformatics platform. Next, we determined the outcome of the intersection of these predicted mRNAs with 100 mRNAs expressed in the above-mentioned five macrophage populations. Based on the screening of miRNA-mRNA pairs, a co-expression network was drawn to find out the key RNAs. Three down-regulated miRNAs and five up-regulated mRNAs were selected for validation by real-time RT-PCR. The results showed that the expression of miR-4498 in plasma exosomes was lower than that in the healthy control, and the expressions of Ctss, Ccr2 and Trem2 mRNA in peripheral blood mononuclear cells isolated from CAD patients were higher. In order to clarify the regulatory mechanism, we established a co-culture system in vitro. Studies have shown that the uptake of exosomes from CAD patients can up-regulate the expression of Ctss, Trem2, and Ccr2 mRNA in THP-1 cells induced by lipopolysaccharide. Our findings revealed a unique relationship between the transcriptional signature and the phenotypic heterogeneity of macrophage in the atherosclerotic microenvironment.

Botanicals as modulators of depression and mechanisms involved.

Depression is the most disastrous mood disorder affecting the health of individuals. Conventional treatments with chemical compounds for depression have limitations, while herbal medicine has unique therapeutic effects. This paper introduces the pharmacological basis and biological mechanisms underlying the botanical antidepressants over the past 5 years. Based upon the specific therapeutic targets or mechanisms, we analyzed the pathological roles of monoamine neurotransmitters, the hypothalamic-pituitary-adrenal axis, inflammation, oxidative stress, synaptic plasticity performed in antidepressant of the botanicals. In addition, gut flora and neurogenesis were also preferentially discussed as treatment approaches. Based on the complex pathogenesis of depression, we suggested that mixed use of botanicals, namely prescription would be more suitable for treatment of depression. In addition, neural circuit affected by botanicals or active components should also attract attention as the botanicals have potential to be developed into fast-acting antidepressants. Finally, gut flora might be a new systemic target for the treatment of depression by botanicals. This review would strength botanical medicine as the antidepressant and also provides an overview of the potential mechanisms involved.

miR-378a Modulates Macrophage Phagocytosis and Differentiation through Targeting CD47-SIRPα Axis in Atherosclerosis.

BACKGROUND: Signal regulatory protein alpha (SIRPa) is an essential signalling molecule that modulates inflammatory responses in macrophages. However, the regulation of SIRPs and its dynamic changes in macrophages under inflammatory stimulation in atherosclerosis remain uncertain. OBJECTIVE: The study aimed to identify the miRNAs that regulate SIRPa transcription and their roles in modulating phagocytosis, differentiation and cholesterol efflux in macrophages. METHODS: ApoE knockout mice were fed with a high-fat diet for 12 weeks. Intimal lesion areas and lipid accumulation were assessed by haematoxylin and eosin (HE) and oil red O staining. The expression of mRNAs/miRNAs was assessed by RNA-seq (RNA sequencing) and RT-qPCR (real-time quantitative polymerase chain reaction). The identification of miR-378a associated with SIRPa regulation in macrophages induced by ox-LDL was confirmed by RT-qPCR and Western blot. The phagocytosis and differentiation of macrophages were detected to figure out the role of miR-378a and SIRPa. RESULTS: SIRPa was proved to be a target of miR-378a. Reduced miR-378a can promote the expression of SIRPa. RNA-seq data showed that the levels of mRNA associated with macrophage phenotypes and SIRPa-CD47 axis were increasing significantly with a decreasing phagocytic phenotype in ApoE-/- mice vs wild-type (WT) mice (P < 0.01). The level of miR-378a was reduced in the aorta of ApoE-/- mice vs WT mice. The experiment in vitro showed that overexpression of miR-378a in macrophages decreased the level of Sirpa mRNA obviously vs control (P < 0.01). The phagocytic activity of miR-378a-transfected macrophages was promoted vs control (P < 0.05). miR-378a significantly depleted Sirpa levels in oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages (P < 0.05), and depletion of miR-378a reversed Sirpa reduction obviously (P < 0.05). miR-378a promoted the secretion of TNF-a and IL-6 indirectly. CONCLUSION: It has been demonstrated that miR-378a regulates SIRPa-mediated phagocytosis and polarization of macrophages by a direct or indirect way. This research may provide a new path to promote reverse cholesterol transport of macrophages and hinder the progress of atherosclerosis.

Tanshinone IIA harmonizes the crosstalk of autophagy and polarization in macrophages via miR-375/KLF4 pathway to attenuate atherosclerosis.

Macrophages play a pivotal role in destabilizing atherosclerotic plaque. The diverse phenotypes and complex autophagy in macrophage are observed in atherosclerotic lesions. Tanshinone IIA (TNA) is known as the major component extracted from the root of Chinese herb Salvia miltiorrhiza, used for treatment of cardiovascular diseases. However, the therapeutic mechanism of TNA is not clear yet. In this study, we identified inflammation-related gene expression by microarray in atherosclerotic plaques in ApoE knockout mice fed with high fat diet and found miR-375 was one of the significantly high expressed microRNAs compared with wild type mice and TNA treated mice. Then we compared the levels of proteins related to the signal pathway of autophagy, and the phenotype of macrophages in atherosclerotic plaques ex vivo. We predicted KLF4 might be the key target of miR-375 that mediated the crosstalk between autophagy and polarization by TNA. Furthermore, we detected the expression of signal pathway in ox-LDL induced macrophages after treatment with TNA in vitro to verify this predict. The results suggest TNA could activate KLF4 and enhance autophagy as well as M2 polarization of macrophages by inhibiting miR-375 to Attenuate Atherosclerosis.