Search

Background This study aims to report the experience of a single center using thoracic endovascular aortic repair (TEVAR) to treat retrograde type A intramural hematoma (IMH) with focal intimal disruption (FID) in descending aorta. Methods A total of 24 consecutive patients with retrograde type A IMH and complicated with FID in descending aorta underwent TEVAR in our center from 2015 to 2020. Their clinical data, imaging manifestation and follow-up results were retrospectively reviewed and analyzed. Results The median age of patients was 57.9 years (range, 42-80 years) and 18 were men (75%). As the preoperative CT angiography showed, the 24 patients developed IMH complicated with different kinds of FIDs in descending aorta [5 had intramural blood pool (IBP), 15 had ulcer-like projection (ULP), 2 had penetrating atherosclerotic ulcer (PAU), and 5 had localized dissection]. Successful deployment of aortic stent graft was achieved in all patients. There was no endoleak, stent graft migration, spinal cord ischemia, stroke, or 30-day mortality observed after TEVAR. The median duration of follow-up was 30.0 months (range, 3-60 months). As the last follow-up CT angiography showed, most of the patients (23 in 24, 96%) had favorable aortic remodeling. The maximum hematoma thicknesses and maximum diameters of both ascending and descending aorta were significantly decreased. During follow-up, 1 patient developed retrograde type A aortic dissection (RAAD) and underwent open surgery 3 months after TEVAR. 1 patient died of lung cancer 2 years later. There was no aorta-related death observed. Conclusions TEVAR provides a safe and effective treatment strategy for selected patients with retrograde type A IMH, and FID developed in descending aorta could be the possible treatment target. However, RAAD remains one of the most serious postoperative complications of concern.

Ke Lei, 1 Bing Ma, 2 Ping Shi, 2 Che Jin, 3 Tan Ling, 1 Longjiang Li, 4 Xiangyi He, 5 Lunchang Wang 1 1Department of Stomatology, Central Hospital of Guangyuan, Guangyuan 628000, People’s Republic of China; 2Department of Respiratory, Central Hospital of Guangyuan, Guangyuan 628000, People’s Republic of China; 3Endodontics Department, Dental Hospital of Lanzhou, Lanzhou 730000, People’s Republic of China; 4State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, People’s Republic of China; 5Department of Prosthodontics, School of Stomatology, Lanzhou University, Lanzhou 730000, People’s Republic of ChinaCorrespondence: Ping ShiDepartment of Respiratory, Central Hospital of Guangyuan, Guangyuan 628000, People’s Republic of ChinaTel/Fax +86 839-3222256Email shi0036369692@163.comBackground: Oral squamous cell carcinoma (OSCC) is an aggressive malignancy worldwide. Icariin (ICA), an active ingredient of flavonoids, has been demonstrated to possess antitumor activity in diverse cancers. Whereas, the role of ICAin OSCC is still unclear.Methods: Herein, we investigated the anti-tumor effects of ICA in vitro and in vivo. CCK-8, colony formation and trans-well assay were used to examined viability, proliferation and invasion in SCC-9 and SCC-15 cell lines, respectively. Next, we tested the expression of toll-like receptor 4 (TLR4) and NF-κB P65 by western blot or immunofluorescence staining. Finally, we constructed a xenograft mice model to investigate the effect of ICA in vivo.Results: In vitro, ICA decreased the human oral squamous cells viability, proliferation and invasion in a concentration-dependent manner. Besides, ICA decreased the phosphorylation level of P65 and down-regulated TLR4 protein. In vivo, compared with control, ICA significantly suppressed the tumor size and weight. In addition, ICA downregulated the levels of Ki67 and VEGF markedly. Dramatically, ICA decreased the phosphorylation level of P65 in tumor tissues.Conclusion: Taken together, ICA could act as a anticancer drug against OSCC to mitigate the growth and invasion ability, the underlying mechanism may due to the down-regulation of TLR4/NF-κB signaling.Keywords: icariin, toll-like receptor 4, oral squamous cell carcinomas, NF-κB

The present study aimed to analyze the experience of a single center and assess the efficacy and durability of endovascular aortic repair (EVAR) in patients with tuberculous infected native aortic aneurysms (INAAs).All patients who underwent EVAR for INAAs between September 2014 and August 2021 were reviewed retrospectively. The primary end points were 30-day and overall mortality rates; the secondary outcomes included major complications, endoleak, recurrence, reintervention rate, and thrombosis of the pseudoaneurysmal sac.A total of 18 patients (average age, 61.3 years; 10 female [55.6%]) were identified. Fifteen patients (83.3%) had adjunctive procedures. Both the in-hospital and 30-day mortality rates were 0%. The overall cumulative survival rates estimated by Kaplan-Meier were 100% at 1 and 6 months, and 92.3% at 12 and 24 months, and 80.8% at 36 and 48 months. Type Ib and II endoleaks each occurred in 1 patient (5.6%) and resolved without treatment after 1 month. No graft infections, strokes, paraplegia, ischemic abdominal complications, or other major complications occurred. The overall rates of cumulative freedom from recurrence of aneurysm and reintervention were 83.9% and 81.8%, respectively, during the median follow-up period of 28.5 months (range, 1-72 months). The median time of administering antituberculosis drugs was 10.5 months (range, 2-44 months).EVAR combined with oral antituberculosis medication is effective and may be an appealing treatment option for patients with high-risk INAAs. Adjunctive procedures, including targeted drug delivery to the site of infection, could be a solution to further controlling the infection, but still needs further evaluation.

Backgrounds: The prognosis of thoracic aortic pseudoaneurysm (TAP) after thoracic endovascular aortic repair (TEVAR) remains unclear. This study investigates the early and midterm clinical outcome as well as relevant risk factors of TAP patients following TEVAR therapy.Methods: From July 2010 to July 2020, 37 eligible TAP patients who underwent TEVAR were selected into our research. We retrospectively explored their baseline, perioperative and follow-up data. Fisher exact test and Kaplan-Meier method were applied for comparing difference between groups. Risk factors of late survival were discerned using Cox regression analysis.Results: There were 29 men and 12 women, with the mean age as 59.5±13.0 years (range, 30-82). The mean follow-up time was 30.7±28.3 months (range, 1-89). For early result, early mortality (≦30days) happened in 3(8.1%) zone 3 TAP patients versus 0 in zone 4 (p= 0.028); acute arterial embolism of lower extremity and type II endoleak respectively occurred in 1(2.7%) case. For midterm result, survival at 3 months, 1 year and 5 years was 88.8±5.3%, 75.9±7.5% and 68.3±9.9%, which showed significant difference between zone 2/3 versus zone 4 group (56.3±14.8% versus 72.9±13.2%, p= 0.013) and emergent versus elective TEVAR groups (0.0±0.0% versus 80.1±8.0%, p= 0.049). On multivariate Cox regression, lesions at zone 2/3 (HR 4.605, 95%CI 1.095-19.359), concomitant cardiac disease (HR 4.932, 95%CI 1.086-22.403) and emergent TEVAR (HR 4.196, 95%CI 1.042-16.891) were significant independent risk factors for worse late clinical outcome. Conclusions: TEVAR therapy is effective and safe with satisfactory early and midterm clinical outcome for TAP patients. Lesions at zone 2/3, concomitant cardiac disease and emergent TEVAR were independent risk factors for midterm survival outcome.

We aimed to establish an animal model of abdominal aortic vascular replacement in mongrel dogs to investigate the effect of extracorporeal radiotherapy on the intima. Twenty healthy mongrel dogs were randomly divided into four groups: 5-week control group, 5-week radiotherapy group, 10-week control group and 10-week radiotherapy group. We first performed an artificial vascular replacement of the abdominal aortic segment. The radiotherapy group received external radiotherapy with a dose of 7 Gy for 4 days. The thickness of neointimal hyperplasia, immunoreactivity and expression of proliferation-related factors were detected by hematoxylin and eosin (HE) staining, immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR )and western blotting at 5 and 10 weeks after the reconstruction. The results showed that the intimal thickness of the artificial blood vessel in the 5- and 10-week radiotherapy groups was thinner than that in the control groups by HE staining. The immunoreactivity and expression levels of Skp2, c-Myc and CyclinE1 were significantly decreased in the radiotherapy groups than those in control groups by immunohistochemistry, qRT-PCR and western blotting. On the contrary, immunoreactivity and expression levels of P27kip1 were increased. In conclusion, we discovered that postoperative external radiotherapy significantly decreases the intimal hyperplasia of artificial blood vessels by regulating c-Myc-Skp2-P27-CyclinE1 network.

Endovascular repair including percutaneous transluminal angioplasty (PTA) and stent implantation has become the standard approach for the treatment of peripheral arterial disease; however, restenosis is still the main limited complication for the long-term success of the endovascular repair. Endothelial denudation and regeneration, inflammatory response, and neointimal hyperplasia are major pathological processes occurring during in-stent restenosis (ISR). MicroRNAs exhibit great potential in regulating several vascular biological events in different cell types and have been identified as novel therapeutic targets as well as biomarkers for ISR prevention. This review summarized recent experimental and clinical studies on the role of miRNAs in ISR modification, with the aim of unraveling the underlying mechanism and potential therapeutic strategy of ISR.

Purpose: To study the effect of x-ray radiotherapy on vascular smooth muscle cells (VSMCs) and elucidate the mechanisms in preventing neointimal hyperplasia of prosthetic vascular grafts. Materials and methods: In model I, twelve mongrel dogs underwent revascularization with prosthetic grafts and half the dogs underwent irradiation of the grafts at 28 Gy. In model II, human VSMCs (hVSMCs) were maintained and divided into six groups to which external radiation was applied at six different doses: 0 Gy, 2 Gy, 8 Gy, 16 Gy, 24 Gy and 30 Gy. In both models, specimens were harvested and examined by using morphological, immunological, cellular and molecular methods. Results: After irradiation, the neointima thickness was significantly lower in irradiated groups (p≤0.01). The radiotherapy could up-regulate p27kip1, and down-regulate proliferating cell nuclear antigen (PCNA) and S phase kinase associated protein 2 (Skp2). X-ray irradiation inhibits the proliferation of hVSMCs via acting on G1/S phase of cell cycle. The apoptosis of hVSMCs increased significantly with dose and time. The expression of PCNA and Skp2 were decreased after a first increasing trend with dose, but had a significant negative correlation with time. The expression of p27kip1 had a significant positive correlation with dose and time. Conclusions: Postoperative external fractionated irradiation after prosthetic vessel replacement of the abdominal aorta suppressed the development of hyperplasia in the graft neointima in the short term. There was a prominent time- and dose-dependent inhibition of VSMC proliferation by radiation when it was administered.

Background: Autologous vein grafting remains the gold standard for surgical bypass grafts. However, vein bypasses still have significant incidence of failure. Ephrin type-B receptor 4 (EphB4), the embryonic venous determinant, may modulate vein graft adaptation. Although EphB4 is expressed in venous endothelial and smooth muscle cells (SMCs), it is not known whether EphB4 is functional in human SMCs. Materials and methods: Human adult venous SMCs were obtained from the inferior vena cava of an adult human liver donor. Primary SMCs were stimulated with EphrinB2/Fc or transfected with an EphB4-expression vector (GV219-EphB4). Expression of SMC phenotype markers, migration, and proliferation were evaluated. Results: Activation of EphB4 with EphrinB2/Fc increased the mRNA and protein expression of the venous SMC contractile markers alpha actin, calponin-1, SM22, and MYH11, while decreasing the expression of the synthetic marker osteopontin. EphrinB2/Fc treatment inhibited SMC migration, but not proliferation. In addition, overexpression of EphB4 increased mRNA expression of SMC contractile markers, while decreasing expression of the apoptosis marker caspase-9. Conclusions: EphB4 was present and functional in adult human venous SMCs. Stimulation of EphB4 increased expression of contractile SMC phenotypic markers and decreased SMC migration in vitro, functioning to retain the contractile phenotype of SMCs. EphB4 activation, therefore, recapitulates changes observed during vein graft adaptation to the arterial environment in vivo. EphB4 represents a new strategy to inhibit neointimal hyperplasia during vein graft adaption.

Rationale Hereditary protein C deficiency has a high prevalence in Asian populations, being the important risk factor associated with thrombophilia. Traditionally, conservative medication is the first choice for patients with hereditary protein C deficiency. However, there are few reports on whether aggressive surgical treatment can be performed when patients continue to develop life-threatening ischemic symptoms after adequate anticoagulant and thrombolytic therapy. Patient concerns A 40-year-old male presented with right lower extremity pain for 1 week. Diagnosis Computed tomography angiography (CTA) of lower extremity indicated arterial embolization of the right superficial femoral artery. Vascular ultrasonography showed old extensive thrombus in the deep vein of the left lower extremity. Electrocardiogram reported old anterior myocardial infarction. Sequencing of the gene encoding protein C (PROC) gene revealed that a heterozygous in-frame deletion mutation (c.577-579delAAG, p.192delK). Based on these findings, the diagnosis of hereditary protein C deficiency was made. Interventions The patient was given low-molecular-weight heparin (LMWH) anticoagulation and urokinase treatment immediately. Then we performed the Fogarty catheter embolectomy with about 18.5 cm thrombus being removed and utilized the balloon catheter to dilate the anterior tibial artery. Despite given adequate anticoagulant and thrombolytic therapy postoperatively, the patient still had new thrombosis, and eventually underwent arterial embolectomy and amputation. Outcomes The patient was discharged with good wound healing and continued rivaroxaban treatment at a dose of 20 mg daily. The patient was followed-up monthly until 1 year: there was no adverse ischemic events occurred. Lessons Aggressive surgical treatment may be the effective attempt for life-saving when conservative treatment as the first choice had unsatisfactory results in hereditary protein C deficiency patients. The novel oral anticoagulants (NOACs) could be more suitable than warfarin for the treatment and prevention of recurrence in patients with hereditary protein C deficiency.

Objectives To characterize the clinical features, treatment, and prognosis of superior mesenteric artery aneurysms and provide evidence for clinical decision-making. Methods We retrospectively reviewed the diagnosis and treatment of 18 cases of superior mesenteric artery aneurysm admitted to our center from 2003 to 2020, including demographic data, risk factors, clinical manifestations, diagnosis, treatment strategies, and follow-up results. Results The average age of the patients was 49.1 years, and males accounted 83.3%. The development of the disease was associated with infection, hypertension, pancreatitis, and trauma, but no significant associations with atherosclerosis were noted by our results. Nine patients were diagnosed with true aneurysm, seven patients with pseudoaneurysm, and two patients with dissecting aneurysm. Rupture of aneurysm occurred in three patients (16.7%), and one of them died before surgery. The surgery success rate was 94.1%, and open surgery was performed on nine patients, endovascular surgery on three patients, and conservative treatment on three patients. The follow-up rate was 77.8% (14/18), and the average follow-up time was 48.2 months. The mortality and reintervention rate during follow-up was 0. The two-year patency rate of artificial vessels and covered stents was 50%. Conclusion The clinical manifestations and features of superior mesenteric artery aneurysms vary between patients. Careful evaluation of vascular anatomy and personalized treatment strategy are critical in the management of superior mesenteric artery aneurysms. Midterm follow-up results of superior mesenteric artery aneurysms are satisfactory.

Ectodysplasin (EDA) gene mutation is associated with hypohidrotic ectodermal dysplasia (HED). The aim of this study was to investigate the effect of ectodysplasin, transcript variant 1 (EDA-A1) on the proliferation and cell cycle of ECV304 human umbilical vein endothelial cells (HUVECs). Recombinant eukaryotic expression vectors containing mutant (M) and wild-type (W) EDA-A1 coding sequences, pcDNA3.1 (-)-EDA-A1-M and pcDNA3.1 (-)-EDA-A1-W, respectively, were transfected into ECV304 cells. The EDA-A1 gene was amplified by reverse transcription polymerase chain reaction (RT-PCR), and the protein was detected by western blotting. The EDA-A1 gene and protein were detected in ECV304 cells transfected with pcDNA3.1 (-)-EDA-A1-M and pcDNA3.1 (-)-EDA-A1-W, but not in ECV304 cells transfected with empty plasmid or cells that had not undergone transfection. Compared with the control group, the EDA-A1 gene mutant significantly decreased the proliferation of ECV304 cells and its inhibition rate was 45.70% (P 0.05). A significant increase of the fraction of cells in the G0/G1 phase of the cell cycle was observed in the ECV304 cells of the mutant group compared with wild type group, with an increase in the S phase population and a concomitant reduction in the G2/M phase population (P

This clinical report describes a relatively infrequent patient with inferior alveolar nerve damage caused by foreign material within the mandibular canal, which is one of the most severe complications of endodontic therapy. Although the circumstance is uncommon, it can have extremely unfavorable consequences for patients, such as anesthesia and paresthesia. In the present case, a patient suffered pain and severe paresthesia in the corresponding area after routine endodontic therapy. Several treatments were conducted to relieve the patient's symptoms, ranging from medication to tooth extraction, but all were of no avail. Ultimately, surgical exploration and debridement were performed with assistance of a customized surgical template. Once the foreign material was excavated, the exacerbation of condition was terminated and gradually reverted. This patient illustrates that special attention is required when undertaking intracanal procedures of lower posterior teeth so as to avoid iatrogenic damage to inferior alveolar nerve. Even more significant, when above-mentioned condition occurs, prompt surgical intervention is essential for recovery of sensation. It also demonstrates the advantages of applying surgical template and piezosurgery in removal of foreign material within the mandibular canal.

Vascular smooth muscle cells (VSMCs) derived from cardiovascular progenitor cell (CVPC) lineage populate the tunica media of the aortic root. Understanding differentiation of VSMCs from CVPC will further our understanding of the molecular mechanisms contributing to aortic root aneurysms, and thus, facilitate the development of novel therapeutic agents to prevent this devastating complication. It is established that the yes-associated protein (YAP) and Hippo pathway is important for VSMC proliferation and phenotype switch. To determine the role of YAP in differentiation of VSMCs from CVPCs, we utilized the in vitro monolayer lineage specific differentiation method by differentiating human embryonic stem cells into CVPCs, and then, into VSMCs. We found that expression of YAP decreased during differentiation of VSMC from CVPCs. Overexpression of YAP attenuated expression of VSMC contractile markers and impaired VSMC function. Knockdown of YAP increased expression of contractile proteins during CVPC-VSMCs differentiation. Importantly, expression of YAP decreased transcription of myocardin during this process. Overexpression of YAP in PAC1 SMC cell line inhibited luciferase activity of myocardin proximal promoter in a dose dependent and NKX2.5 dependent manners. YAP protein interacted with NKX2.5 protein and inhibited binding of NKX2.5 to the 5′-proximal promoter region of myocardin in CVPC-derived VSMCs. In conclusion, YAP negatively regulates differentiation of VSMCs from CVPCs by decreasing transcription of myocardin in a NKX2.5-dependent manner.

The rock pigeon (Columba livia), or Rock dove, is a member of the bird family Columbidae. We mapped the complete mitochondrial genome of the Rock pigeon. The mitochondrial genome of this species is a circular molecule of 17,229 bp in length, encoding a standard set of 13 protein-coding genes, two ribosomal RNA genes, and 22 transfer RNA genes, plus a putative control region, demonstrating a structure very similar to that of other birds. As found in other vertebrates, most of these genes are coded on the H-strand, except for NADH dehydrogenase subunit 6 (nad6) and eight tRNA genes (Gln, Ala, Asn, Cys, Tyr, Ser(UCN), Pro, Glu). The AT skew and GC skew of the whole genome, protein-coding genes, tRNA, rRNA, and the control region were calculated for the complete mitochondrial genomes of 30 avian species, representing 29 orders. All protein-coding genes initiated with ATG, except for cox1 and nad5, which began with GTG. One extra nucleotide 'C' was present in NADH dehydrogenase subunit 3 (nad3). All tRNA gene sequences have the potential to fold into typical cloverleaf secondary structures. Within the control region, conserved sequences were identified in three domains. Although the conserved blocks, such as ETAS1, ETAS2, CSB1, CSB1-like, and boxes C, D, E, and F, are readily identifiable in the C. livia control region, the typical origin of H-strand replication (O(H)), CSB2 and CSB3 could not be detected. These results provide basic information for phylogenetic analyses of birds, especially Columbiformes species.

Cardiovascular disease is the leading cause of mortality worldwide. Current surgical treatments for cardiovascular disease include vascular bypass grafting and replacement with autologous blood vessels or synthetic vascular grafts. However, there is a call for better alternative biological grafts.Tissue-engineered vascular grafts (TEVGs) are promising novel alternatives to replace diseased vessels. However, obtaining enough functional and clinically usable vascular cells for fabrication of TEVGs remains a major challenge. New findings in adult stem cells and recent advances in pluripotent stem cells have opened a new avenue for stem cell-based vascular engineering. In this review, recent advances on stem cell sourcing for TEVGs including the use of adult stem cells and pluripotent stem cells and advantages, disadvantages, and possible future implementations of different types of stem cells will be discussed. In addition, current strategies used during the fabrication of TEVGs will be highlighted.The application of patient-specific TEVGs constructed with vascular cells derived from immune-compatible stem cells possesses huge clinical potential. Advances in lineage-specific differentiation approaches and innovative vascular engineering strategies will promote the vascular regeneration field from bench to bedside.

Individuals with bicuspid aortic valves (BAV) are at a high risk to develop a thoracic aortic aneurysms (TAA) than patients with trileaflet aortic valves (TAV), most commonly involving ascending aorta and sparing the descending aorta. Smooth muscle cells (SMCs) in the ascending and descending aorta arise from neural crest and paraxial mesoderm, respectively. We hypothesize the aortopathy associated with BAVs is due to aberrant differentiation of neural crest stem cells (NCSCs) to SMCs. Induced pluripotent stem cell (iPSC) lines were established from a patient with BAV/TAA, and control patients with TAV and a normal aorta. The iPSCs pluripotency was verified by standard stem cell markers and teratoma formation in SCID mice. iPSCs were differentiated into NCSCs and paraxial mesoderm cells (PMCs) separately, and verified by specific neural crest markers and paraxial mesoderm markers. Both NCSCs and PMCs were differentiated into SMCs, NCSC-SMCs and PMC-SMCs, by treating with TGFβ1 and PDGF-bb. With differentiation, both SMCs lines expressed SMC specific markers including MYH11, CNN1, ACTA2, and TAGLN by quantitative RT-PCR and immunohistochemical staining. However, NCSC-derived SMCs from BAV/TAA patient demonstrated significantly decreased expression and protein levels of MYH11 and ACTA2 and impaired contraction by gel contraction assay compared to NCSC-SMCs derived from control. In contrast, the PMC-derived SMCs from BAV/TAAD patient had similar or higher expression and levels of contractile proteins, including MYH11, CNN1, ACTA2, and TAGLN, and contractile response to carbacol treatment when compared with control PMC-SMCs. The defective differentiation of NCSC-SMC from the BAV/TAA patient was coupled with the decreased TGFβ signaling as assessed by decreased gene expression of TGFβ1 and connective tissue growth factor (CTGF) when compared to control cells. Increasing the concentration of TGFβ1, rescued the gene expressions of TGFβ1, CTGF, MYH11 and ACTA2 in the NCSC-SMCs from the BAV/TAA. Taken together, our data demonstrate that defective TGFβ signaling and differentiation of specifically NCSC-derived SMCs contributes to aortopathy in BAV with ascending aortic aneurysm.

Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates antioxidant and anti-inflammatory genes, and it plays a crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Moreover, 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2) plays a protective role against oxidative stress and inflammation both in vivo and in vitro. In a previous study, we found that 15d-PGJ2 increased the expression of Nrf2 in a COPD rat model. This study aims to elucidate the role of 15d-PGJ2 in COPD pathogenesis and the relationship between Nrf2 and human bronchial epithelial (HBE) cells. Normal HBE (HBE) cells were cultured. Following cigarette smoke extract (CSE) stimulation, pre-incubation with or without small interfering RNA (siRNA) Nrf2, and stimulation with or without 15d-PGJ2, the expression levels of Nrf2, NF-κBp65, and IL-8 were detected by reverse transcription-polymerase chain reaction and western blot, respectively. The expression of NF-κBp65 and IL-8 in CSE-stimulated normal HBE cells was inhibited by 15d-PGJ2 at both the mRNA level and the protein level. Moreover, the expression of Nrf2 in normal HBE cells was improved by 15d-PGJ2 at both the mRNA level and the protein level. However, the inhibitory or improving effects of 15d-PGJ2 were disengaged by siRNA Nrf2 at both the mRNA level and the protein level. 15d-PGJ2 possesses anti-inflammatory properties in the pathogenesis of COPD, and HBE cells stimulated by CSE via Nrf2 activation.

Tissue-engineered blood vessels (TEBVs) are promising in regenerating a live vascular replacement. However, the vascular cell source is limited, and it is crucial to develop a scaffold that accommodates new type of vascular progenitor cells and facilitates in vivo lineage specification of the cells into functional vascular smooth muscle cells (VSMCs) to regenerate vascular tissue. In the present study, integration-free human induced pluripotent stem cells (hiPSCs) were established from patient peripheral blood mononuclear cells through episomal vector nucleofection of reprogramming factors. The established hiPSCs were then induced into mesoderm-originated cardiovascular progenitor cells (CVPCs) with a highly efficient directed lineage specification method. The derived CVPCs were demonstrated to be able to differentiate into functional VSMCs. Subcutaneous implantation of CVPCs seeded on macroporous nanofibrous poly(l-lactide) scaffolds led to in vivo VSMC lineage specification and matrix deposition inside the scaffolds. In summary, we established integration-free patient-specific hiPSCs from peripheral blood mononuclear cells, derived CVPCs through directed lineage specification, and developed an advanced scaffold for these progenitor cells to further differentiate in vivo into VSMCs and regenerate vascular tissue in a subcutaneous implantation model. This study has established an efficient patient-specific approach towards in vivo regeneration of vascular tissue.

Ascending aortic aneurysm occurs in 35%-68% patients with bicuspid aortic valves (BAV), which is more frequently than it does in patients with normal trileaflet aortic valves (TAV). In contrast to recurrent aneurysms of the ascending aorta, descending aortic aneurysms is very rare in patients with BAV. Vascular Smooth Muscle Cells (SMCs) make up the media of the aortic walls, and their contractile properties help sustain vessel tone. Interestingly, ascending aorta is populated by SMCs arising from neural crest and descending aorta by SMCs from paraxial mesoderm. An intriguing hypothesis is that the distinct susceptibility of aneurysm in the ascending and descending aorta in patients with BAV is due in part to disparities in SMC embryonic origins. To prove our hypothesis, we used an induced Pluripotent Stem Cells (iPS) model system to generate SMCs from neural crest and paraxial mesoderm. Firstly, iPSCs were established from a patient with BAV and ascending thoracic aortic aneurysm (BAV/TAA) and two control patients with normal aorta and TAV. The iPSCs pluripotency was verified by standard stem cell markers and teratoma formation. Neural crest stem cells (NCSCs) were differentiated from iPSCs and expressed neural crest markers, including P75, HNK1, AP2 and Sox9. In parallel, paraxial mesoderm cells (PMCs) were differentiated from iPSCs and expressed specific markers, including TCF15, TBX6, Meox1 and Pax1. The SMCs differentiated from both lineages had expression of SMC markers including MYH11, CNN1, ACTA2, SM22α. Interestingly, SMCs derived from BAV-NCSCs had significantly decreased in MYH11 and ACTA2 gene expression and impaired contractile property by gel contraction assay compared to SMCs derived from control-NCSCs. However, SMCs from BAV-PMCs had similar level of expression of MYH11 and ACTA2, and strong contractile activity with Carbacol treatment compared to SMCs derived from control PMCs. In conclusion, the iPS model system revealed decreased expression of contractile proteins and impairment of contractility in SMCs derived from NCSCs in BAV patient, but not in the SMCs derived from paraxial mesoderm cells. The high susceptibility of aneurysm in the ascending aorta in patients with BAV might be partly due to embryonic origin of the SMCs.

Ectodysplasin (EDA) gene mutation is associated with hypohidrotic ectodermal dysplasia (HED). The aim of this study was to investigate the effect of ectodysplasin, transcript variant 1 (EDA-A1) on the proliferation and cell cycle of ECV304 human umbilical vein endothelial cells (HUVECs). Recombinant eukaryotic expression vectors containing mutant (M) and wild-type (W) EDA-A1 coding sequences, pcDNA3.1 (−)-EDA-A1-M and pcDNA3.1 (−)-EDA-A1-W, respectively, were transfected into ECV304 cells. The EDA-A1 gene was amplified by reverse transcription polymerase chain reaction (RT-PCR), and the protein was detected by western blotting. The EDA-A1 gene and protein were detected in ECV304 cells transfected with pcDNA3.1 (−)-EDA-A1-M and pcDNA3.1 (−)-EDA-A1-W, but not in ECV304 cells transfected with empty plasmid or cells that had not undergone transfection. Compared with the control group, the EDA-A1 gene mutant significantly decreased the proliferation of ECV304 cells and its inhibition rate was 45.70% (P0.05). A significant increase of the fraction of cells in the G0/G1 phase of the cell cycle was observed in the ECV304 cells of the mutant group compared with wild type group, with an increase in the S phase population and a concomitant reduction in the G2/M phase population (P