Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis.

Production of amphiregulin (Areg) by regulatory T (Treg) cells promotes repair after acute tissue injury. Here, we examined the function of Treg cells in non-alcoholic steatohepatitis (NASH), a setting of chronic liver injury. Areg-producing Treg cells were enriched in the livers of mice and humans with NASH. Deletion of Areg in Treg cells, but not in myeloid cells, reduced NASH-induced liver fibrosis. Chronic liver damage induced transcriptional changes associated with Treg cell activation. Mechanistically, Treg cell-derived Areg activated pro-fibrotic transcriptional programs in hepatic stellate cells via epidermal growth factor receptor (EGFR) signaling. Deletion of Areg in Treg cells protected mice from NASH-dependent glucose intolerance, which also was dependent on EGFR signaling on hepatic stellate cells. Areg from Treg cells promoted hepatocyte gluconeogenesis through hepatocyte detection of hepatic stellate cell-derived interleukin-6. Our findings reveal a maladaptive role for Treg cell-mediated tissue repair functions in chronic liver disease and link liver damage to NASH-dependent glucose intolerance.

An Anatomic Classification Scheme for Surgical Planning of Renal Artery Aneurysms.

PURPOSE: Renal artery aneurysm (RAA) is a rare disease. This study proposed and evaluated a new classification for RAA to assist in surgical decision-making. MATERIALS AND METHODS: Single-center data of 105 patients with RAAs from the vascular department of vascular surgery were collected retrospectively. A new classification scheme was proposed. Type I aneurysms arise from the main trunk, accessory branch, or first-order branches away from any bifurcation. Type II aneurysms arise from the first bifurcation with narrow necks (defined as dome-to-neck ratio >2) or from intralobular branches. Type III aneurysms with a wide neck arise from the first bifurcation and affect 2 or more branches that cannot be sacrificed without significant infarction of the kidney. RESULTS: There was 50 (47.62%) type I, 33 (31.43%) type II, and 22 (20.95%) type III aneurysms. The classification assigned endovascular repair as first-line treatment (for type I or II), while open techniques were conducted if anatomically suitable (for type III). A kappa level of 0.752 was achieved by the classification compared with a level of 0.579 from the classic Rundback classification. Technical primary success was achieved in 100% and 96.05%, and symptoms were completely resolved in 100% and 84.85%, while hypertension was relieved in 84.21% and 72.92% of patients receiving open surgery or endovascular repair, respectively. No significant difference was observed for perioperative or long-term complications among the 3 classification types. CONCLUSION: The new classification proved to be a convenient and effective method for facilitating choice of intervention for RAAs. CLINICAL IMPACT: This study proposed and evaluated a new classification scheme for renal artery aneurysms, which proved to be a convenient and effective method for facilitating surgical decision-making. Coil embolization was the first-line treatment if suitable, while aneurysm resection and reconstruction with vein graft were conducted for some complex lesions. The safety and efficacy of both open and endovascular methods were validated.

Efficient Generation of Murine Chimeric Antigen Receptor (CAR)-T Cells.

Engineered cell therapies utilizing chimeric antigen receptor (CAR)-T cells have achieved remarkable effectiveness in individuals with hematological malignancies and are presently undergoing development for the treatment of diverse solid tumors. So far, the preliminary evaluation of novel CAR-T cell products has predominantly taken place in xenograft tumor models using immunodeficient mice. This approach is chosen to facilitate the successful engraftment of human CAR-T cells in the experimental setting. However, syngeneic mouse models, in which tumors and CAR-T cells are derived from the same mouse strain, allow evaluation of new CAR technologies in the context of a functional immune system and comprehensive tumor microenvironment (TME). The protocol described here aims to streamline the process of mouse CAR-T cell generation by presenting standardized methods for retroviral transduction and ex vivo T cell culture. The methods described in this protocol can be applied to other CAR constructs beyond the ones used in this study to enable routine evaluation of new CAR technologies in immune-competent systems.

Tumor Explants Elucidate a Cascade of Paracrine SHH, WNT, and VEGF Signals Driving Pancreatic Cancer Angiosuppression.

The sparse vascularity of pancreatic ductal adenocarcinoma (PDAC) presents a mystery: What prevents this aggressive malignancy from undergoing neoangiogenesis to counteract hypoxia and better support growth? An incidental finding from prior work on paracrine communication between malignant PDAC cells and fibroblasts revealed that inhibition of the Hedgehog (HH) pathway partially relieved angiosuppression, increasing tumor vascularity through unknown mechanisms. Initial efforts to study this phenotype were hindered by difficulties replicating the complex interactions of multiple cell types in vitro. Here we identify a cascade of paracrine signals between multiple cell types that act sequentially to suppress angiogenesis in PDAC. Malignant epithelial cells promote HH signaling in fibroblasts, leading to inhibition of noncanonical WNT signaling in fibroblasts and epithelial cells, thereby limiting VEGFR2-dependent activation of endothelial hypersprouting. This cascade was elucidated using human and murine PDAC explant models, which effectively retain the complex cellular interactions of native tumor tissues. SIGNIFICANCE: We present a key mechanism of tumor angiosuppression, a process that sculpts the physiologic, cellular, and metabolic environment of PDAC. We further present a computational and experimental framework for the dissection of complex signaling cascades that propagate among multiple cell types in the tissue environment. This article is featured in Selected Articles from This Issue, p. 201.

A Laplacian Pyramid Based Generative H&E Stain Augmentation Network.

Hematoxylin and Eosin (H&E) staining is a widely used sample preparation procedure for enhancing the saturation of tissue sections and the contrast between nuclei and cytoplasm in histology images for medical diagnostics. However, various factors, such as the differences in the reagents used, result in high variability in the colors of the stains actually recorded. This variability poses a challenge in achieving generalization for machine-learning based computer-aided diagnostic tools. To desensitize the learned models to stain variations, we propose the Generative Stain Augmentation Network (G-SAN) - a GAN-based framework that augments a collection of cell images with simulated yet realistic stain variations. At its core, G-SAN uses a novel and highly computationally efficient Laplacian Pyramid (LP) based generator architecture, that is capable of disentangling stain from cell morphology. Through the task of patch classification and nucleus segmentation, we show that using G-SAN-augmented training data provides on average 15.7% improvement in F1 score and 7.3% improvement in panoptic quality, respectively. Our code is available at https://github.com/lifangda01/GSAN-Demo.

Generation and ex vivo culture of murine and human pancreatic ductal adenocarcinoma tissue slice explants.

Traditional 2D/3D co-culture models typically do not reflect the cellular heterogeneity of pancreatic ductal adenocarcinoma (PDAC) tumors, while in vivo models can be slow and ill-suited to mechanistic investigations. Here, we present a protocol for culturing murine PDAC explants and a corresponding human PDAC model using tissue slice explants. We describe steps for sponge production, preparation of media and materials, tissue collection, and sectioning. We then detail procedures for explant plating, daily culture, and collection of samples.

Probiotic-guided CAR-T cells for solid tumor targeting.

A major challenge facing tumor-antigen targeting therapies such as chimeric antigen receptor (CAR)-T cells is the identification of suitable targets that are specifically and uniformly expressed on heterogeneous solid tumors. By contrast, certain species of bacteria selectively colonize immune-privileged tumor cores and can be engineered as antigen-independent platforms for therapeutic delivery. To bridge these approaches, we developed a platform of probiotic-guided CAR-T cells (ProCARs), in which tumor-colonizing probiotics release synthetic targets that label tumor tissue for CAR-mediated lysis in situ. This system demonstrated CAR-T cell activation and antigen-agnostic cell lysis that was safe and effective in multiple xenograft and syngeneic models of human and mouse cancers. We further engineered multifunctional probiotics that co-release chemokines to enhance CAR-T cell recruitment and therapeutic response.

Identification of potential drug targets for varicose veins: a Mendelian randomization analysis.

Introduction: Varicose veins are a common chronic disease that creates a significant economic burden on the healthcare system. Current treatment options, including pharmacological treatments, are not always effective, and there is a need for more targeted therapies. A Mendelian randomization (MR) method uses genetic variants as instrumental variables to estimate the causal effect of an exposure on an outcome, and it has been successful in identifying therapeutic targets in other diseases. However, few studies have used MR to explore potential protein drug targets for varicose veins. Methods: To identify potential drug targets for varicose veins of lower extremities, we undertook a comprehensive screen of plasma protein with a two-sample MR method. We used recently reported cis-variants as genetic instruments of 2,004 plasma proteins, then applied MR to a recent meta-analysis of genome-wide association study on varicose veins (22,037 cases and 437,665 controls). Furthermore, pleiotropy detection, reverse causality testing, colocalization analysis, and external replication were utilized to strengthen the causal effects of prioritized proteins. Phenome-wide MR (PheW-MR) of the prioritized proteins for the risk of 525 diseases was conducted to screen potential side effects. Results: We identified eight plasma proteins that are significantly associated with the risk of varicose veins after Bonferroni correction (P < 2.495 × 10-5), with five being protective (LUM, POSTN, RPN1, RSPO3, and VAT1) and three harmful (COLEC11, IRF3, and SARS2). Most identified proteins showed no pleiotropic effects except for COLLEC11. Bidirectional MR and MR Steiger testing excluded reverse causal relationship between varicose veins and prioritized proteins. The colocalization analysis indicated that COLEC11, IRF3, LUM, POSTN, RSPO3, and SARS2 shared the same causal variant with varicose veins. Finally, seven identified proteins replicated with alternative instruments except for VAT1. Furthermore, PheW-MR revealed that only IRF3 had potential harmful adverse side effects. Conclusions: We identified eight potential causal proteins for varicose veins with MR. A comprehensive analysis indicated that IRF3, LUM, POSTN, RSPO3, and SARS2 might be potential drug targets for varicose veins.

Blood pressure and renal outcomes after renal artery aneurysm intervention: Single-center experience and review of literature.

Objective: To explore the results of hypertension improvement and renal function preservation after renal artery aneurysm (RAA) repair. Methods: This study retrospectively analyzed the change in blood pressure (BP) and renal outcomes of 59 RAA patients throughout either open or endovascular operations and follow-up at a large center. Patients were grouped according to the difference in their BP at the last follow-up vs. their baseline value. Logistic regression was conducted to explore risk factors for perioperative BP relief and long-term hypertension reonset. Previous studies of RAA with records of BP, blood creatinine level, or GFR/eGFR results are reviewed. Results: Hypertension was observed in 62.7% (37/59) of the patients included. Postoperative BP declined from 132.20 ± 16.46/79.92 ± 9.64 mmHg to 122.41 ± 11.17/71.10 ± 9.82 mmHg, while eGFR changed from 108.17 ± 24.73 to 98.92 ± 23.87 ml/min/1.73 m2. The median follow-up was 854 [IQR: 1,405] days. Both open and endovascular techniques significantly relieved hypertension and did not impair renal function much. Lower preoperative systolic BP (SBP) was significantly associated with hypertension relief (OR = 0.83, 95% CI: 0.70-0.99). Among patients with normal BP after the operation, higher postoperative SBP was significantly associated with new-onset hypertension (OR = 1.14, 95% CI: 1.01-1.29). Literature review indicated that renal function usually remained normal at follow-up, whereas relief of hypertension varied. Conclusion: Patients with lower preoperative SBP were likely to benefit more from the operation, while higher postoperative SBP indicated a higher chance of hypertension reonset. Creatinine level and eGFR generally remained stable regardless of operation type.

Long Term Outcomes and Potential Risk Factors for Endovascular Repair of Aortic Pseudoaneurysms in Vascular Behçet's Disease.

OBJECTIVE: This study aimed to analyse long term outcomes and risk factors for endovascular repair of aortic pseudoaneurysms in patients with vascular Behçet's disease (BD). METHODS: Medical records of 26 aortic vascular BD patients who underwent endovascular treatment at the vascular department of Peking Union Medical College Hospital between January 2002 and December 2021 were reviewed retrospectively. Erythrocyte sedimentation rate (ESR) and C reactive protein were used to assess BD activity. Computed tomography angiography (CTA) was obtained pre- and post-operatively for almost all patients. Univariable logistic regression analysis was used to analyse risk factors for endovascular repair, such as inflammatory indicators, drug usage, and stent graft parameters. RESULTS: The abdominal aorta (n = 17) was the most common site of 27 vascular BD pseudoaneurysms in this study. CTA also revealed one aortic arch pseudoaneurysm, seven descending thoracic aortic pseudoaneurysms, one thoraco-abdominal aortic pseudoaneurysm, and one pseudoaneurysm at the aortic bifurcation. Most of the pseudoaneurysms were treated with covered stent grafts. The technical success rate was 96% and no deaths occurred during hospital stay. The mean follow up was 5.8 ± 5.5 years and 31% (8/26) experienced post-operative complications. Overall one, three, and five year event free survival rates were 87%, 78%, and 74%, respectively. Univariable logistic regression analysis revealed that pre-operative ESR ≥ 16.0 mm/h (p = .040), pre-operative glucocorticoid (GC) use ≤ 11.5 days (p = .024), pre-operative immunosuppressant use ≤ 15.5 days (p = .028), and length of proximal landing zone ≤ 1.95 cm (p = .034) were associated with a worse prognoses following endovascular treatment. Proximal oversize ≥ 9.5% (p = .074) was also regarded as a risk factor, although not statistically significant. CONCLUSION: This study further confirmed the feasibility of endovascular repair for aortic vascular BD patients. Risk factors predicting poor prognoses included elevated pre-operative ESR, insufficient pre-operative GC use or immunosuppressant use, inadequate proximal landing zone, and larger proximal oversize percentage.

Chemokines expressed by engineered bacteria recruit and orchestrate antitumor immunity.

Tumors use multiple mechanisms to actively exclude immune cells involved in antitumor immunity. Strategies to overcome these exclusion signals remain limited due to an inability to target therapeutics specifically to the tumor. Synthetic biology enables engineering of cells and microbes for tumor-localized delivery of therapeutic candidates previously unavailable using conventional systemic administration techniques. Here, we engineer bacteria to intratumorally release chemokines to attract adaptive immune cells into the tumor environment. Bacteria expressing an activating mutant of the human chemokine CXCL16 (hCXCL16K42A) offer therapeutic benefit in multiple mouse tumor models, an effect mediated via recruitment of CD8+ T cells. Furthermore, we target the presentation of tumor-derived antigens by dendritic cells, using a second engineered bacterial strain expressing CCL20. This led to type 1 conventional dendritic cell recruitment and synergized with hCXCL16K42A-induced T cell recruitment to provide additional therapeutic benefit. In summary, we engineer bacteria to recruit and activate innate and adaptive antitumor immune responses, offering a new cancer immunotherapy strategy.

Identification of Novel Plasma Biomarkers for Abdominal Aortic Aneurysm by Protein Array Analysis.

Abdominal aortic aneurysm (AAA) is a potentially life-threatening disease that is common in the aging population. Currently, there are no approved diagnostic biomarkers or therapeutic drugs for AAA. We aimed to identify novel plasma biomarkers or potential therapeutic targets for AAA using a high-throughput protein array-based method. Proteomics expression profiles were investigated in plasma from AAA patients and healthy controls (HC) using 440-cytokine protein array analysis. Several promising biomarkers were further validated in independent cohorts using enzyme-linked immunosorbent assay (ELISA). Thirty-nine differentially expressed plasma proteins were identified between AAA and HC. Legumain (LGMN) was significantly higher in AAA patients and was validated in another large cohort. Additionally, "AAA without diabetes" (AAN) patients and "AAA complicated with type 2 diabetes mellitus" (AAM) patients had different cytokine expression patterns in their plasma, and nine plasma proteins were differentially expressed among the AAN, AAM, and HC subjects. Delta-like protein 1 (DLL1), receptor tyrosine-protein kinase erbB-3 (ERBB3), and dipeptidyl peptidase 4 (DPPIV) were significantly higher in AAM than in AAN. This study identified several promising plasma biomarkers of AAA. Their role as therapeutic targets for AAA warrants further investigation.

[Effects of Leptin and Leptin-associated Signaling Pathways on the Occurrence and Progression of Abdominal Aortic Aneurysms].

Abdominal aortic aneurysm(AAA) is a chronic dilated artery disease induced by atherosclerosis,infection,trauma and other related causes.The available studies about AAA mainly focus on the inflammatory response,senility,and microenvironmental changes,while the research on the metabolic changes such as glucose metabolism and lipid metabolism remains to be conducted.As a critical regulatory factor in endocrine,glucose,and lipid metabolisms,leptin is associated with a variety of signaling pathways such as adenosine monophosphate-activated protein kinase,Janus kinase/signal transducer and activator of transcription,and cytokine-cytokine receptor,as demonstrated by the KEGG pathway enrichment analysis.Moreover,these signaling pathways are generally involved in regulating the occurrence of AAA.In addition,leptin affects the occurrence of a variety of diseases such as obesity,diabetes,and hyperlipidemia,which contribute to the formation of AAA.Diabetes might be a protective factor for the formation of AAA,while the relationship of hyperlipidemia and obesity with the formation of AAA remains unclear.Therefore,leptin might play an essential role in the formation of AAA.Further studies about the effect of leptin on AAA may provide the potential research direction and facilitate the discovery of therapeutic targets.

The molecular mechanism of Ang II induced-AAA models based on proteomics analysis in ApoE-/- and CD57BL/6J mice.

Apolipoprotein knockout (ApoE-/-) and CD57BL/6J mouse models of angiotensin II (Ang II)-induced abdominal aortic aneurysm (AAA) are commonly used in AAA research. However, the similarities and differences in the molecular mechanisms of AAA in these two genotypes have not been reported. In our study, we analyzed proteomics data from ApoE-/- and CD57BL/6J mouse models of Ang II-induced AAA and control mice by LC-MS/MS. Gene set enrichment analysis (GSEA) of differentially abundance proteins (DAPs) in the ApoE-/- or CD57BL/6J mouse groups was performed in R software, and infiltration of immune cells in groups was assessed. DAP that showed the same trend in abundance in ApoE-/- and CD57BL/6J mice (S-DAP) were identified and subjected to GO enrichment, KEGG pathway, and connectivity map (CMap) analyses. The protein-protein interaction (PPI) network of the S-DAP was drawn, the key S-DAP were identified by MCODE, and the transcription factors (TFs) of crucial S-DAP were predicted by iRegulon in Cytoscape. Male ApoE-/- and CD57BL/6J mouse models of Ang II-induced AAA are commonly used in AAA research, and extracellular matrix organization is associated with AAA in both of these models. However, there are some differences between the mechanisms underlying AAA in these two genotypes, and these differences need to be considered when studying AAA and selecting models. SIGNIFICANCE: Our research provided the first insight into the similarity and differential mechanisms of Ang II infused AAA models using ApoE-/- and CD57BL/6J mice. This study might provide the some advises for the selection of Ang II infused AAA models for further AAA researches.

Key ferroptosis-related genes in abdominal aortic aneurysm formation and rupture as determined by combining bioinformatics techniques.

Objectives: Abdominal aortic aneurysm (AAA) is a cardiovascular disease with high mortality and pathogenesis closely related to various cell death types, e.g., autophagy, apoptosis and pyroptosis. However, the association between AAA and ferroptosis is unknown. Methods: GSE57691 and GSE98278 dataset were obtained from the Gene Expression Omnibus database, and a ferroptosis-related gene (FRG) set was downloaded from the FerrDb database. These data were normalized, and ferroptosis-related differentially expressed genes (FDEGs, AAA vs. normal samples) were identified using the limma package in R. FRGs expression was analyzed by Gene Set Expression Analysis (GSEA), and FDEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) pathway enrichment analyses using the clusterProfiler package in R and ClueGO in Cytoscape. Protein-protein interaction networks were assembled using Cytoscape, and crucial FDEGs were identified using CytoHubba. Critical FDEG transcription factors (TFs) were predicted with iRegulon. FDEGs were verified in GSE98278 set, and key FDEGs in AAA (compared with normal samples) and ruptured AAA (RAAA; compared with AAA samples) were identified. Ferroptosis-related immune cell infiltration and correlations with key genes were analyzed by CIBERSORT. Key FEDGs were reverified in Ang II-induced AAA models of ApoE-/- and CD57B/6J mice by immunofluorescence assay. Results: In AAA and normal samples, 40 FDEGs were identified, and the expression of suppressive FRGs was significantly downregulated with GSEA. For FDEGs, the GO terms were response to oxidative stress and cellular response to external stimulus, and the KEGG pathways were the TNF and NOD-like receptor signaling pathways. IL6, ALB, CAV1, PTGS2, NOX4, PRDX6, GPX4, HSPA5, HSPB1, and NCF2 were the most enriched genes in the crucial gene cluster. CEBPG, NFAT5, SOX10, GTF2IRD1, STAT1, and RELA were potential TFs affecting these crucial genes. Ferroptosis-related immune cells involved in AAA formation were CD8+ T, naive CD4+ T, and regulatory T cells (Tregs); M0 and M2 macrophages; and eosinophils. Tregs were also involved in RAAA. GPX4, SLC2A1, and PEBP1 expression was downregulated in both the RAAA and AAA samples. GPX4 and PEBP1 were more important in AAA because they influenced ferroptosis-related immune cell infiltration, and SLC2A1 was more important in RAAA. Conclusions: This is the first study to show that ferroptosis is crucial to AAA/RAAA formation. The TNF and NOD-like signaling pathways and ferroptosis-related immune cell infiltration play key roles in AAA/RAAA. GPX4 is a key ferroptosis-related gene in AAA. Ferroptosis and related genes might be promising targets in the treatment of AAA/RAAA.

Blood pressure control and renal function preservation of ex vivo renal artery repair with orthotopic renal autotransplantation for complex renal artery diseases.

OBJECTIVE: To assess the outcome of ex vivo renal artery repair with orthotopic renal autotransplantation for patients with complex renal artery disease. METHODS: The single-center study collected and analyzed the data from patients with complex renal artery disease undergoing ex vivo renal artery repair with orthotopic renal autotransplantation, retrospectively. RESULTS: A total of 21 complex renal artery lesions from 19 patients were included. The mean blood pressure showed a significant decrease from the preoperative to the postoperative period (P < .05). Renal function kept stable for the perioperative period. No significant serum creatinine and estimated glomerular filtration rate alteration was observed compared with the immediate postoperative period (P = .439 and .904, respectively). The median renal cold ischemia time was 35.5 (76) minutes. Two patients developed perioperative complications, one with acute cholecystitis and one with acute renal failure after graft occlusion in a solitary kidney. During the median follow-up of 48 months, one single bypass graft of a solitary kidney was occluded, and four grafts developed restenosis. The primary and primary-assisted patency rates at the 5-year follow-up were 81.3% and 87.5%, respectively. No deaths were observed in the follow-up period. CONCLUSIONS: Ex vivo renal artery reconstruction with orthotopic renal autotransplantation in patients with complex renal artery disease offers stable control of blood pressure and renal function preservation, and should be considered as a potential alternative for other open surgical procedures.

A programmable encapsulation system improves delivery of therapeutic bacteria in mice.

Living bacteria therapies have been proposed as an alternative approach to treating a broad array of cancers. In this study, we developed a genetically encoded microbial encapsulation system with tunable and dynamic expression of surface capsular polysaccharides that enhances systemic delivery. Based on a small RNA screen of capsular biosynthesis pathways, we constructed inducible synthetic gene circuits that regulate bacterial encapsulation in Escherichia coli Nissle 1917. These bacteria are capable of temporarily evading immune attack, whereas subsequent loss of encapsulation results in effective clearance in vivo. This dynamic delivery strategy enabled a ten-fold increase in maximum tolerated dose of bacteria and improved anti-tumor efficacy in murine models of cancer. Furthermore, in situ encapsulation increased the fraction of microbial translocation among mouse tumors, leading to efficacy in distal tumors. The programmable encapsulation system promises to enhance the therapeutic utility of living engineered bacteria for cancer.

Delphinidin-3-O-glucoside, an active compound of Hibiscus sabdariffa calyces, inhibits oxidative stress and inflammation in rabbits with atherosclerosis.

CONTEXT: Delphinidin-3-O-glucoside (DP) is a bioactive compound of Hibiscus sabdariffa L. (Malvaceae) (Roselle) calyces and exerts endothelial protection and lipid-lowering activities, which provided a basis for the prevention and treatment of cardiovascular diseases. OBJECTIVES: To investigate the therapeutic effects of DP against atherosclerosis. MATERIALS AND METHODS: A rabbit model of atherosclerosis (AS) was established by 12 weeks of a high-fat diet (HFD). The rabbits were divided into five groups: control, AS, simvastatin (4 mg/kg), and two DP groups (10 and 20 mg/kg). After treatment with DP or simvastatin by oral gavage for 12 weeks, the lipid profiles were measured. Histopathological assessment of the aorta was performed by H&E staining. Oxidative stress and inflammation-related markers were analyzed by ELISA kit and real-time RT-PCR. RESULTS: DP (20 mg/kg) decreased serum TG (2.36 ± 0.66 vs. 4.33 ± 0.27 mmol/L for the AS group), TC, LDL-C, and HDL-C (all p < 0.05). DP (20 mg/kg) also reduced lipid levels in the liver and aorta. DP (20 mg/kg) down-regulated the mRNA levels of IL-6, VCAM-1, and NF-κB and up-regulated the mRNA levels of GSH-PX and SOD1. CONCLUSIONS: This study proved that DP alleviated the HFD-induced oxidative stress and inflammation in atherosclerosis rabbits. These results provided the scientific basis for developing novel therapies.

[Differences of Gut Microbiota Diversity between Patients with Abdominal Aortic Aneurysm and Atherosclerosis].

Objective To investigate the differences of gut microbiota between patients with abdominal aortic aneurysm and atherosclerosis.Methods From December 2018 to June 2019,20 fresh stool samples were collected respectively from the patients with abdominal aortic aneurysm and atherosclerosis treated at the Department of Vascular Surgery,Peking Union Medical College Hospital.The 16S rDNA high-throughput sequencing was employed to compare the composition,abundance,and α and ß diversities of gut microbiota between the two disease groups,and further determine the significantly differential genera.Results The two groups had great similarities in the composition of gut microbiota.There was no statistical difference in α diversity.Although ß diversity did not have statistically significant difference,certain microbial taxa showed differences between the two groups.The LEfSe demonstrated that the abdominal aortic aneurysm group had higher relative abundance of Leuconostocaceae,Ruminococcaceae,Weissella,and Faecalibacterium while lower relative abundance of Firmicuteria,Selenomonadales,and Veillonellaceae.Conclusion The structure of gut microbiota has differences between patients with abdominal aortic aneurysm and atherosclerosis,and sample size should be enlarged to validate the results.