CD147 monoclonal antibody attenuates abdominal aortic aneurysm formation in angiotensin II-Infused apoE-/- mice.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a life threatening vascular disease. Our previous study reported the upregulation of CD147 expression in human aortic aneurysms. OBJECTIVE: In this study, we injected apoE-/- mice intraperitoneally with CD147 monoclonal antibody or IgG control antibody to observe its effect on Angiotensin II (AngII) induced AAA formation. METHODS: ApoE-/- mice were randomly divided into an AngⅡ+CD147 antibody group (n = 20) and an AngⅡ+IgG antibody group (n = 20). The Alzet osmotic minipump was implanted subcutaneously into the backs of mice to infuse AngII (1000 ng/kg/min) for 28 days and subsequently treated with CD147 monoclonal antibody or control IgG mAb (10 µg/mouse/day) beginning one day after surgery. Body weight, food intake, drinking volume and blood pressure were measured weekly throughout the study. After 4 weeks of injection, routine bloodwork measuring liver function, kidney function and lipid levels were recorded. Hematoxylin and eosin (H&E), Masson's trichrome, and Elastic van Gieson (EVG) staining were used to evaluate the pathological changes in blood vessels. In addition, Immunohistochemical assay was used to detect infiltration of inflammatory cells. Tandem mass tag (TMT)-based proteomic analysis was used to define differentially expressed proteins (DEPs) using a p-value < 0.05 and fold change > 1.2 or < 0.83 as the threshold. Subsequently, we conducted protein-protein interaction (PPI) network and GO enrichment analysis to determine the core biological function altered after CD147 antibody injection. RESULTS: The CD147 monoclonal antibody suppresses Ang II-induced AAA formation in apoE-/- mice and reduced aortic expansion, elastic lamina degradation, and inflammatory cells accumulation. Bioinformatics analysis showed that Ptk6, Itch, Casp3, and Oas1a were the hub DEPs. These DEPs in the two group were mainly involved in collagen fibril organization, extracellular matrix organization, and muscle contraction. These data robustly demonstrated that CD147 monoclonal antibody suppresses Ang II-induced AAA formation through reduction of inflammatory response and regulation of the above defined hub proteins and biological processes. Thus, the CD147 monoclonal antibody might be a promising target in the treatment of abdominal aortic aneurysm.

Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic Dissection.

Purpose: This study aims to illustrate the cellular landscape in the aorta of experimental aortic dissection (AD) and elaborate on the smooth muscle cells (SMCs) heterogeneity and functions among various cell types. Methods: Male Apolipoprotein deficient (ApoE-/-) mice at 28 weeks of age were infused with Ang II (2,500 ng/kg/min) to induce AD. Aortas from euthanized mice were harvested after 7 days for 10×Genomics single-cell RNA sequencing (scRNA-seq), followed by the identification of cell types and differentially expressed genes (DEGs). Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted. Results: AD was successfully induced in ApoE-/- mice. scRNA-seq identified 15 cell clusters and nine cell types, including non-immune cells (endothelials, fibroblasts, and SMCs) and immune cells (B cells, natural killer T cell, macrophages, dendritic cells, neutrophils, and mast cells). The relative numbers of SMCs were remarkably changed, and seven core DEGs (ACTA2,IL6,CTGF,BGN,ITGA8,THBS1, and CDH5) were identified in SMCs. Moreover, we found SMCs can differentiate into 8 different subtypes through single-cell trajectory analysis. Conclusion: scRNA-seq technology can successfully identify unique cell composition in experimental AD. To our knowledge, this is the first study that provided the complete cellular landscape in AD tissues from mice, seven core DEGs and eight subtypes of SMCs were identified, and the SMCs have evolution from matrix type to inflammatory type.

Blunt aortic injury-traumatic aortic isthmus pseudoaneurysm with right iliac artery dissection aneurysm: A case report.

BACKGROUND: Blunt aortic injury is a special type of aortic disease. Due to its low incidence, high prehospital mortality and high probability of leakage diagnosis, the timely identification of patients with blunt aortic injury who survive the initial injury has always been a clinical challenge. CASE SUMMARY: We report a case of traumatic aortic pseudoaneurysm with right iliac artery dissection aneurysm that was diagnosed 3 mo after a traffic accident. The patient is a 76-year-old male who was knocked down by a fast-moving four-wheel motor vehicle while crossing the road (the damage mechanism was side impact). He received chest, cranial computed tomography (CT) and whole abdomen enhanced CT in the local hospital. The images suggested subarachnoid hemorrhage, right frontoparietal scalp hematoma, fracture of the right clavicle and second rib, lump-shaped mediastinal shadow outside the anterior descending thoracic aorta (mediastinal hematoma), mesenteric vascular injury with hematoma formation, pelvic fracture, and subluxation of the left sacroiliac joint. After the pelvic fracture was fixed with an external stent, he was sent to our hospital for further treatment. In our hospital, he successfully underwent partial resection of the small intestine and CT-guided screw internal fixation of the left sacroiliac joint and returned to the local hospital for rehabilitation treatment. However, since the accident, the patient has been suffering from mild chest pain, which has not aroused the attention of clinicians. During rehabilitation, his chest pain gradually worsened, and the thoracic aorta computed tomography angiography performed in the local hospital showed a pseudoaneurysm in the initial descending segment of the aortic arch. After transfer to our hospital, a dissecting aneurysm of the right external iliac artery was incidentally found in the preoperative evaluation. Finally, endovascular stent graft repair was performed, and he was discharged on the 10th day after the operation. No obvious endo-leak was found after 4 years of follow-up. CONCLUSION: We highlight that emergency trauma centers should consider the possibility of aortic injury in patients with severe motor vehicle crashes and repeat the examination when necessary to avoid missed diagnoses.

Saikosaponin D Inhibited IL-1ß Induced ATDC 5 Chondrocytes Apoptosis In Vitro and Delayed Articular Cartilage Degeneration in OA Model Mice In Vivo.

Osteoarthritis (OA) is the most common joint disease in the elderly, characterized by cartilage degradation and proliferation of subchondral bone. The pathogenesis of OA involves a variety of inflammatory mediators, including nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß. From the molecular mechanism, the nuclear factor-erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) pathway and the expression of ROS regulated the production of the above inflammatory mediators. Saikosaponin D (SSD), which is an active ingredient isolated from Bupleurum, has various biological functions. In this study, IL-1ß was used as a pro-inflammatory factor to create an in vitro OA model. According to the results of high-density culture, qPCR, ROS measurement, Western blot, and immunofluorescence, SSD activated the Nrf2/HO-1/ROS axis, inhibited the production of inflammatory mediators, and protected against ECM destruction. The DMM mouse model was used as a model of OA in mice. From the results of safranin O/fast green staining, hematoxylin-eosin staining, tartrate-resistant acid phosphatase (TRAP) staining, and OARSI scores, SSD protected against the mice knee articular cartilage degeneration and reduced the number of osteoclasts in the subchondral bone. Experimental results found that SSD suppressed IL-1ß-induced differentiated ATDC 5 chondrocytes apoptosis via the Nrf2/HO-1/ROS axis in vitro. SSD delayed the progression of OA in DMMs model mice in vivo. Therefore, SSD has the potential to become a drug for clinical treatment of OA.

Potential influencing factors of aortic diameter at specific segments in population with cardiovascular risk.

BACKGROUND: Aortic diameter is a critical parameter for the diagnosis of aortic dilated diseases. Aortic dilation has some common risk factors with cardiovascular diseases. This study aimed to investigate potential influence of traditional cardiovascular risk factors and the measures of subclinical atherosclerosis on aortic diameter of specific segments among adults. METHODS: Four hundred and eight patients with cardiovascular risk factors were prospectively recruited in the observational study. Comprehensive transthoracic M-mode, 2-dimensional Doppler echocardiographic studies were performed using commercial and clinical diagnostic ultrasonography techniques. The aortic dimensions were assessed at different levels: (1) the annulus, (2) the mid-point of the sinuses of Valsalva, (3) the sinotubular junction, (4) the ascending aorta at the level of its largest diameter, (5) the transverse arch (including proximal arch, mid arch, distal arch), (6) the descending aorta posterior to the left atrium, and (7) the abdominal aorta just distal to the origin of the renal arteries. Multivariable linear regression analysis was used for evaluating aortic diameter-related risk factors, including common cardiovascular risk factors, co-morbidities, subclinical atherosclerosis, lipid profile, and hematological parameters. RESULTS: Significant univariate relations were found between aortic diameter of different levels and most traditional cardiovascular risk factors. Carotid intima-media thickness was significantly correlated with diameter of descending and abdominal aorta. Multivariate linear regression showed potential effects of age, sex, body surface area and some other cardiovascular risk factors on aortic diameter enlargement. Among them, high-density lipoprotein cholesterol had a significantly positive effect on the diameter of ascending and abdominal aorta. Diastolic blood pressure was observed for the positive associations with diameters of five thoracic aortic segments, while systolic blood pressure was only independently related to mid arch diameter. CONCLUSION: Aortic segmental diameters were associated with diastolic blood pressure, high-density lipoprotein cholesterol, atherosclerosis diseases and other traditional cardiovascular risk factors, and some determinants still need to be clarified for a better understanding of aortic dilation diseases.

Inhibition of Lipopolysaccharide-Induced Inflammatory Bone Loss by Saikosaponin D is Associated with Regulation of the RANKL/RANK Pathway.

BACKGROUND: Osteolytic diseases such as osteoporosis are featured with accelerated osteoclast differentiation and strong bone resorption. Considering the complications and other limitations of current drug treatments, it is necessary to develop a safer and more reliable drug to deal with osteoclast-related diseases. Saikosaponin D (SSD) is the active extract of Bupleurum, which has anti-inflammation, anti-tumor and liver protection functions. However, the role of SSD in regulating the differentiation and function of osteoclasts is not clear. PURPOSE: To explore whether SSD could prevent osteoclast differentiation and bone resorption induced by M-CSF and RANKL, and further evaluate the potential therapeutic properties of SSD in LPS-induced inflammatory bone loss mouse models. METHODS: BMMs were cultured in complete medium stimulated by RANKL with different concentrations of SSD. TRAP staining, bone resorption determination, qRT-PCR, immunofluorescence and Western blotting were performed. A mouse model of LPS-induced calvarial bone loss was established and treated with different doses of SSD. The excised calvaria bones were used for TRAP staining, micro-CT scan and histological analysis. RESULTS: SSD inhibited the formation and bone resorption of osteoclasts induced by RANKL in vitro. SSD suppressed LPS-induced inflammatory bone loss in vivo. CONCLUSION: SSD inhibited osteoclastogenesis and LPS-induced osteolysis in mice both which served as a new potential agent for the treatment of osteoclast-related conditions.

Research Progress of Automated Visual Surface Defect Detection for Industrial Metal Planar Materials.

The computer-vision-based surface defect detection of metal planar materials is a research hotspot in the field of metallurgical industry. The high standard of planar surface quality in the metal manufacturing industry requires that the performance of an automated visual inspection system and its algorithms are constantly improved. This paper attempts to present a comprehensive survey on both two-dimensional and three-dimensional surface defect detection technologies based on reviewing over 160 publications for some typical metal planar material products of steel, aluminum, copper plates and strips. According to the algorithm properties as well as the image features, the existing two-dimensional methodologies are categorized into four groups: statistical, spectral, model, and machine learning-based methods. On the basis of three-dimensional data acquisition, the three-dimensional technologies are divided into stereoscopic vision, photometric stereo, laser scanner, and structured light measurement methods. These classical algorithms and emerging methods are introduced, analyzed, and compared in this review. Finally, the remaining challenges and future research trends of visual defect detection are discussed and forecasted at an abstract level.