Biogenesis, Mode of Action and the Interactions of Plant Non-Coding RNAs.

The central dogma of genetics, which outlines the flow of genetic information from DNA to RNA to protein, has long been the guiding principle in molecular biology. In fact, more than three-quarters of the RNAs produced by transcription of the plant genome are not translated into proteins, and these RNAs directly serve as non-coding RNAs in the regulation of plant life activities at the molecular level. The breakthroughs in high-throughput transcriptome sequencing technology and the establishment and improvement of non-coding RNA experiments have now led to the discovery and confirmation of the biogenesis, mechanisms, and synergistic effects of non-coding RNAs. These non-coding RNAs are now predicted to play important roles in the regulation of gene expression and responses to stress and evolution. In this review, we focus on the synthesis, and mechanisms of non-coding RNAs, and we discuss their impact on gene regulation in plants.

Comparison of pulmonary function changes between patients receiving neoadjuvant chemotherapy and chemoradiotherapy prior to minimally invasive esophagectomy: a randomized and controlled trial.

PURPOSE: Adequate pulmonary function is important for patients undergoing surgical resection of esophageal cancer, especially those that received neoadjuvant therapy. However, it is unknown if pre-operative radiation affects pulmonary function differently compared to chemotherapy. The purpose of this study was to compare changes in pulmonary function between patients undergoing minimally invasive esophagectomy (MIE) who received neoadjuvant chemotherapy or chemoradiotherapy. METHODS: Between March 2017 and March 2018, esophageal cancer patients requiring neoadjuvant therapy were prospectively enrolled and randomly assigned to receive chemotherapy (CT) or chemoradiotherapy (CRT) before MIE. All patients received pulmonary function testing before and after the neoadjuvant therapy. Changes in pulmonary function, operative data, and pulmonary complications were compared between the 2 groups. RESULTS: A total of 71 patients were randomized and underwent MIE after receiving CT (n = 34) or CRT (n = 37). Baseline clinical characteristics were comparable between the 2 groups. The CRT group experienced a greater decrease of forced expiratory volume at 1 s (FEV1) (2.66 to 2.18 L, p = 0.023) and diffusion capacity of the lung for carbon monoxide divided by the mean alveolar volume (DLCO/Va) (17.3%, p < 0.001) than the CT group (FEV1 2.53 to 2.41 L; DLCO/Va 4.8%). The incidence of pulmonary complications was higher in the CRT group (13.51 vs. 8.82%), but the difference was not significant (p = 0.532). CONCLUSIONS: Preoperative CRT affects pulmonary function more than CT alone, but does not increase the risk of pulmonary complications in patients undergoing MIE.

Oestrogen Receptor ß Activation Protects Against Myocardial Infarction via Notch1 Signalling.

PURPOSE: Oestrogen receptor ß is believed to exert a cardioprotective effect against ischaemic injury. Nonetheless, the mechanism underlying its protective action remains to be fully elucidated. Recently, increased attention has been focused on Notch1 signalling for ameliorating cardiac ischaemic injury. Here, we hypothesised that oestrogen receptor ß activation attenuates myocardial infarction (MI)-induced cardiac damage by modulating the Notch1 signalling pathway. METHODS: Male C57BL/6 mice were used to establish an MI model through the ligation of the anterior descending branch of the left coronary artery. Two chemical drugs, 2,3-Bis(4-hydroxyphenyl)-propionitrile (DPN) and N-[N-(3,5-difluorophenacetyl)-l-alanyl]-s-phenylglycine t-butyl ester (DAPT), a specific inhibitor of Notch1 signalling) were administered via intraperitoneal injection to change oestrogen receptor ß and Notch1 activities. Immunohistochemistry, western blot analysis, enzyme-linked immunosorbent assay (Elisa) assessment and echocardiography were used in this study to analyse cardiac oxidative stress, apoptosis, infraction volume, fibrosis and cardiac function. RESULTS: DPN-mediated oestrogen receptor ß activation effectively protected cardiomyocytes from MI-induced oxidative damage and apoptosis. Furthermore, oestrogen receptor ß activation reduced the infarct size and lowered the levels of myocardial enzymes in the serum, thereby leading to greater overall cardiac function improvement. Ischaemic injury-induced myocardial fibrosis was attenuated by oestrogen receptor ß activation. Nevertheless, all of these cardioprotective effects of oestrogen receptor ß activation were almost abrogated by DAPT administration, i.e. DAPT attenuated the anti-oxidative and anti-apoptotic effects and the decrease in infarct and fibrotic areas and reversed cardiac functional recovery. The levels of phospho-phosphatidylinositol-3-kinase (PI3K) and phospho-protein kinase B (Akt) were increased after DPN administration, and this change was reversed after DAPT was administered. CONCLUSIONS: All of these new findings indicate that oestrogen receptor ß activation is effective in ameliorating MI-induced cardiac dysfunction by enhancing Notch1 signalling and that PI3K/Akt signalling is the downstream mediator.

Inhibition of Peptidyl Arginine Deiminase-4 Prevents Renal Ischemia-Reperfusion-Induced Remote Lung Injury.

Ischemia reperfusion (IR) can lead to acute kidney injury and can be complicated by acute lung injury, which is one of the leading causes of acute kidney injury-related death. Peptidyl arginine deiminase-4 (PAD4) is a member of the PAD enzyme family and plays a critical role in inflammatory reactions and neutrophil extracellular trap formation in a variety of pathological conditions. It has been reported that PAD4 inhibition can protect certain organs from ischemic injury. In this study, we aimed to understand the mode of action of PAD4 in renal ischemia-reperfusion-mediated acute lung injury. Bilateral renal pedicle occlusion was induced for 30 min followed by reperfusion for 24 h. A specific inhibitor of PAD4, GSK484, was delivered via intraperitoneal injection to alter the PAD4 activity. The pulmonary PAD4 expression, pulmonary impairment, neutrophil infiltration, Cit-H3 expression, neutrophil extracellular trap formation, inflammatory cytokine secretion, and pulmonary apoptosis were analyzed. We found that renal ischemia reperfusion was associated with pulmonary pathological changes and increases in neutrophil infiltration, neutrophil extracellular trap formation, and inflammatory cytokine secretion in the lungs of the recipient animals. Suppression of PAD4 by GSK484 reduced remote lung injury by mitigating neutrophil infiltration, neutrophil extracellular trap formation, apoptosis, and inflammatory factor secretion. Our findings demonstrate that specific PAD4 inhibition by GSK484 may be an effective strategy to attenuate distant lung injury complicating renal ischemia-reperfusion injury.

Estrogen Receptor α and ß in Mouse: Adipose-Derived Stem Cell Proliferation, Migration, and Brown Adipogenesis In Vitro.

BACKGROUND/AIMS: Adipose-derived stem cells (ASCs) belong to mesenchymal stem cells and may play a potential role as seeding cells in stem cell transplantation. To be able to exploit stem cells as therapeutic tool, their defects in some important cellular functions, such as low survival rate and cellular activity, should be considered. This is especially the case for stem cells that are intended for transplantation. Of note, stem cell responses to hormones should be considered since estrogen is known to play a critical role in stem cell behavior. However, different impacts of the estrogen receptor (ER) types α and ß have not been fully determined in ASC function. In this study, we investigated effects of ERα and ERß on ASC proliferation, migration, as well as in adipogenesis. METHODS: ASCs obtained from mice were cultured with 100nM ERα or ERß agonist PPT and DPN, respectively. The ERα and ERß antagonist ICI 182,780 (100nM) was used as control. RESULTS: Compared to ERß, ERα appears more potent in improving ASC proliferation and migration. Investigation of adipogenesis revealed that ERß played a significant role in suppressing ASC-mediated brown tissue adipogenesis which is in contrast to ERα. These results correlated with reduced mRNA expression of UCP-1, PGC-1α and PPAR-x03B3;. CONCLUSIONS: ERα plays a more critical role in promoting ASC proliferation and migration while ERß is more potent in suppressing ASC brown adipose tissue differentiation mediated by decreased UCP-1, PGC-1α and PPAR-x03B3; expression.

Surfactant-enhanced bioremediation of petroleum-contaminated soil and microbial community response: A field study.

Surfactant-enhanced bioremediation (SEBR) is frequently employed to clean up soil polluted with petroleum hydrocarbons, but few studies have focused on how surfactants affect microbial communities and different fractions of petroleum hydrocarbons, particularly in the field. Here, the surfactants sodium dodecyl benzene sulfonate (SDBS), alpha olefin sulfonate (AOS), Triton X-100 (TX-100), Tween80, and rhamnolipid were combined with the oil-degrading bacterium Pseudomonas sp. SB to remediate oil-contaminated soil in the laboratory. AOS gave the highest removal efficiency (65.1%) of total petroleum hydrocarbons (TPHs). Therefore, AOS was used in a field experiment with Pseudomonas sp. SB and the removal efficiency of TPHs and long-chain hydrocarbons C21-C40 reached 57.4 and 53.0%, respectively, significantly higher than the other treatments. During bioremediation the addition of Pseudomonas sp. SB significantly stimulated the growth of bacterial genera such as Alcanivorax, Luteimonas, Parvibaculum, Stenotrophomonas, and Pseudomonas and AOS further stimulated the growth of Sphingobacterium, Pseudomonas and Alcanivorax. This study validates the feasibility of surfactant-enhanced bioremediation in the field and partly reveals the mechanism of surfactant-enhanced bioremediation from the perspective of changes in different fractions of petroleum and microbial community dynamics.

Integrating multiple machine learning methods to construct glutamine metabolism-related signatures in lung adenocarcinoma.

Background: Glutamine metabolism (GM) is known to play a critical role in cancer development, including in lung adenocarcinoma (LUAD), although the exact contribution of GM to LUAD remains incompletely understood. In this study, we aimed to discover new targets for the treatment of LUAD patients by using machine learning algorithms to establish prognostic models based on GM-related genes (GMRGs). Methods: We used the AUCell and WGCNA algorithms, along with single-cell and bulk RNA-seq data, to identify the most prominent GMRGs associated with LUAD. Multiple machine learning algorithms were employed to develop risk models with optimal predictive performance. We validated our models using multiple external datasets and investigated disparities in the tumor microenvironment (TME), mutation landscape, enriched pathways, and response to immunotherapy across various risk groups. Additionally, we conducted in vitro and in vivo experiments to confirm the role of LGALS3 in LUAD. Results: We identified 173 GMRGs strongly associated with GM activity and selected the Random Survival Forest (RSF) and Supervised Principal Components (SuperPC) methods to develop a prognostic model. Our model's performance was validated using multiple external datasets. Our analysis revealed that the low-risk group had higher immune cell infiltration and increased expression of immune checkpoints, indicating that this group may be more receptive to immunotherapy. Moreover, our experimental results confirmed that LGALS3 promoted the proliferation, invasion, and migration of LUAD cells. Conclusion: Our study established a prognostic model based on GMRGs that can predict the effectiveness of immunotherapy and provide novel approaches for the treatment of LUAD. Our findings also suggest that LGALS3 may be a potential therapeutic target for LUAD.

Distributed Averaging Problems of Agriculture Picking Multi-Robot Systems via Sampled Control.

Distributed control of agriculture picking multi-robot systems has been widely used in the field of smart agriculture, this paper aims to explore the distributed averaging problems of agriculture picking multi-robot systems under directed communication topologies by taking advantage of the sampled data. With the algebraic graph theory concepts and the matrix theory, a distributed protocol is proposed based on the nearest sampled neighbor information. It is shown that under the proposed protocol, the states of all agents can be guaranteed to reach average consensus whose value is the averaging of the initial states of all agents. Besides, when considering time-delay, the other distributed protocol is constructed, in which a time margin of the time-delay can be determined simultaneously. The necessary and sufficient consensus results can be developed even though the time delay exists. Simulation results are given to demonstrate the effectiveness of our developed consensus results.

A Combined Approach for Accurate and Accelerated Teeth Detection on Cone Beam CT Images.

Teeth detection and tooth segmentation are essential for processing Cone Beam Computed Tomography (CBCT) images. The accuracy decides the credibility of the subsequent applications, such as diagnosis, treatment plans in clinical practice or other research that is dependent on automatic dental identification. The main problems are complex noises and metal artefacts which would affect the accuracy of teeth detection and segmentation with traditional algorithms. In this study, we proposed a teeth-detection method to avoid the problems above and to accelerate the operation speed. In our method, (1) a Convolutional Neural Network (CNN) was employed to classify layer classes; (2) images were chosen to perform Region of Interest (ROI) cropping; (3) in ROI regions, we used a YOLO v3 and multi-level combined teeth detection method to locate each tooth bounding box; (4) we obtained tooth bounding boxes on all layers. We compared our method with a Faster R-CNN method which was commonly used in previous studies. The training and prediction time were shortened by 80% and 62% in our method, respectively. The Object Inclusion Ratio (OIR) metric of our method was 96.27%, while for the Faster R-CNN method, it was 91.40%. When testing images with severe noise or with different missing teeth, our method promises a stable result. In conclusion, our method of teeth detection on dental CBCT is practical and reliable for its high prediction speed and robust detection.

Further Results for Edge Convergence of Directed Signed Networks.

The edge convergence problems have been explored for directed signed networks recently in 2019 by Du, Ma, and Meng, of which the analysis results, however, depend heavily on the strong connectivity of the network topologies. The question asked in this article is: whether and how can the edge convergence be achieved when the strong connectivity is not satisfied? The answer for the case of spanning tree is given. It is shown that if a signed network is either structurally balanced or r-structurally unbalanced, then the edge state can be ensured to converge to a constant vector. In contrast, if a signed network is both structurally unbalanced and r-structurally balanced, then its edge state does not converge to a constant vector any longer, but to a time-varying vector trajectory with a constant speed. Further, the dynamic behavior results of edges can be derived to address the node convergence problems of signed networks. The simulation examples are provided to illustrate the validity of the established edge convergence results.

Distributed Controller Design and Analysis of Second-Order Signed Networks With Communication Delays.

This article concentrates on dealing with distributed control problems for second-order signed networks subject to not only cooperative but also antagonistic interactions. A distributed control protocol is proposed based on the nearest neighbor rules, with which necessary and sufficient conditions are developed for consensus of second-order signed networks whose communication topologies are described by strongly connected signed digraphs. Besides, another distributed control protocol in the presence of a communication delay is designed, for which a time margin of the delay can be determined simultaneously. It is shown that under the delay margin condition, necessary and sufficient consensus results can be derived even though second-order signed networks with a communication delay are considered. Simulation examples are included to illustrate the validity of our established consensus results of second-order signed networks.

Highly Efficient MicroRNA Delivery Using Functionalized Carbon Dots for Enhanced Conversion of Fibroblasts to Cardiomyocytes.

INTRODUCTION: The reprogramming of induced cardiomyocytes (iCMs) is of particular significance in regenerative medicine; however, it remains a great challenge to fabricate an efficient and safe gene delivery system to induce reprogramming of iCMs for therapeutic applications in heart injury. Here, we report branched polyethyleneimine (BP) coated nitrogen-enriched carbon dots (BP-NCDs) as highly efficient nanocarriers loaded with microRNAs-combo (BP-NCDs/MC) for cardiac reprogramming. METHODS: The BP-NCDs nanocarriers were prepared and characterized by several analytical techniques. RESULTS: The BP-NCDs nanocarriers showed good microRNAs-combo binding affinity, negligible cytotoxicity, and long-term microRNAs expression. Importantly, BP-NCDs/MC nanocomplexes led to the efficient direct reprogramming of fibroblasts into iCMs without genomic integration and resulting in effective recovery of cardiac function after myocardial infarction (MI). CONCLUSION: This study offers a novel strategy to provide safe and effective microRNAs-delivery nanoplatforms based on carbon dots for promising cardiac regeneration and disease therapy.

Inhibition of peptidyl arginine deiminase-4 protects against myocardial infarction induced cardiac dysfunction.

Peptidyl arginine deiminase-4 (PAD4), a PAD enzyme family member, catalyzes the posttranslational conversion of arginine residues to citrulline in target proteins. Although PAD4 is believed to play a crucial role in various pathological conditions such as infectious diseases, autoimmune diseases, and ischemic conditions, the effect of PAD4 in myocardial infarction (MI)-induced cardiac injury remains to be examined. Here, we hypothesize that PAD4 contributes to cardiac ischemic injury by exacerbating the inflammatory response and promoting neutrophil extracellular trap (NET) formation after MI. Permanent left coronary artery ligation, a condition that mimics MI, was performed on male C57BL/6 mice. [(3S,4R)-3-amino-4-hydroxy-1-piperidinyl] [2-[1-(cyclopropylmethyl)-1H-indol-2-yl]-7-methoxy-1-methyl-1H-benzimidazol-5-yl]-methanone (GSK484), an inhibitor of PAD4, was delivered via intraperitoneal injection to inhibit PAD4 activity. Cardiac PAD4 expression, tissue injury scoring, neutrophil infiltration, cit-H3 expression, NET formation, inflammatory cytokine secretion, apoptosis, and cardiac function were analyzed. In the current study, we discovered the protective effect of PAD4 inhibition using the PAD4-specific inhibitor GSK484 in cardiomyocytes challenged by MI. GSK484-mediated PAD4 inhibition can moderately preserve ventricle histological structure and myocardium integrity after MI, thereby reducing the infarct size and decreasing myocardial enzyme levels in serum. PAD4 inhibition also effectively protects cardiomyocytes from MI-induced NET formation and inflammatory cytokine secretion, in turn alleviating cardiac ischemia-induced apoptosis of cardiomyocytes. Collectively, these findings demonstrate the efficacy of specific PAD4 inhibition in reducing MI-induced neutrophil infiltration, NET formation, inflammatory reaction, and cardiomyocyte apoptosis, thereby increasing overall cardiac function improvement. These results provide novel insights for the development of new strategies to treat cardiovascular dysfunction in MI patients.

Edge Convergence Problems on Signed Networks.

This paper focuses on characterizing edge dynamics of signed networks subject to both cooperative and antagonistic interactions and copes with the state convergence problems of the resulting edge systems. To represent the two competitive classes of interactions that emerge in signed networks, signed digraphs are adopted and the relevant edge Laplacian matrices are introduced, with which an edge-based distributed protocol is presented. The relation between the edge Laplacian matrix and the structural balance (or unbalance) of a signed digraph is disclosed by taking advantage of properties of undirected cycles. Further, it is shown that for a signed network, the state of its edge system converges to a constant vector, regardless of whether its associated signed digraph is structurally balanced or unbalanced. This result does not need to impose the assumption upon the digon sign-symmetry of the signed digraph that is generally required by the node-based distributed protocols. In particular, the state convergence results of edges can be exploited to handle traditional bipartite consensus problems for the nodes of signed networks. Simulation examples are given to illustrate the effectiveness of the edge-based analysis method proposed for signed networks.

Silk fibroin/poly(L-lactic acid-co-ε-caprolactone) electrospun nanofibrous scaffolds exert a protective effect following myocardial infarction.

Electrospinning using biocompatible polymer scaffolds, seeded with or without stem cells, is considered a promising technique for producing fibrous scaffolds with therapeutic possibilities for ischemic heart disease. However, no optimal scaffolds for treating ischemic heart disease have been identified thus far. In the present study, it was evaluated whether electrospun silk fibroin (SF)-blended poly(L-lactic acid-co-ε-caprolactone) [P(LLA-CL)] scaffolds that were seeded with cluster of differentiation 117 (c-kit)+ bone marrow (BM) cells may serve a protective role in cardiac remodeling following myocardial infarction (MI). Mechanical characteristics and cytocompatibility were compared between SF/P(LLA-CL) and P(LLA-CL) electrospun nanofibrous scaffolds in vitro. It was observed that MI led to a significant increase of the c-kit+ BM cell subpopulation in mice. Magnetic activated cell sorting was performed to harvest the c-kit+ cell population from the BM of mice following MI. c-kit+ BM cells were seeded on SF/P(LLA-CL) and P(LLA-CL) electrospun nanofibrous scaffolds. Results indicated that SF/P(LLA-CL) electrospun nanofibrous scaffolds were superior to P(LLA-CL) electrospun nanofibrous scaffolds in improving c-kit+ BM cell proliferation. Additionally, compared with pure SF/P(LLA-CL) electrospun nanofibrous scaffolds, SF/P(LLA-CL) scaffolds seeded with c-kit+ BM cells resulted in lower levels of MI markers and reduced infarct size, leading to greater global heart function improvement in vivo. The findings of the present study indicated that SF/P(LLA-CL) electrospun nanofibrous scaffolds seeded with c-kit+ BM cells exert a protective effect against MI and may be a promising approach for cardiac regeneration after ischemic heart disease.

Glia maturation factor beta is required for reactive gliosis after traumatic brain injury in zebrafish.

Gliosis is a hallmark of neural pathology that occurs after most forms of central nervous system (CNS) injuries including traumatic brain injury (TBI). Identification of genes that control gliosis may provide novel treatment targets for patients with diverse CNS injuries. Glia maturation factor beta (GMFB) is crucial in brain development and stress response. In the present study, GMFB was found to be widely expressed in adult zebrafish telencephalon. A gmfb mutant zebrafish was created using CRISPR/cas9. In the uninjured zebrafish telencephalon, glial fibrillary acidic protein (GFAP) fibers in gmfb mutants were disorganized and shorter than wild type zebrafish. After TBI, transformation of quiescent type I radial glial cells (RGC) to proliferative type II RGCs was significantly suppressed in the gmfb mutant. RGC proliferation and hypertrophy post-TBI was reduced in gmfb mutants, indicating that reactive gliosis was attenuated. TBI-induced acute inflammation was also found to be alleviated in the gmfb mutant. Morphological changes also suggest attenuation of microglial reactive gliosis. In a mouse model of TBI, GMFB expression was increased around the injury site. These GMFB+ cells were identified as astrocytes and microglia. Taken together, the data suggests that GMFB is not only required for normal development of GFAP fibers in the zebrafish telencephalon, but also promotes reactive gliosis after TBI. Our findings provide novel information to help better understand the reactive gliosis process following TBI.

Characterization and functional elucidation of CD8+AT2+ lymphocytes in human thoracic aortic aneurysm.

Human thoracic aortic aneurysm (TAA) is one of the most fatal cardiovascular diseases. However, the underlying molecular mechanism behind this disease remains uncertain. Previous studies have proven the importance of angiotensin II receptor type 2 (AT2) and endothelial cells in aneurysm pathology. This study aimed to elucidate the effect of CD8+AT2+ lymphocytes in TAA pathogenesis. The expression levels of CD8, AT2, IL-2, and IFN-r were determined by real-time quantitative PCR. CD8+AT2+ lymphocytes were counted by semi-quantitative immunofluorescence and flow cytometric analysis. The wound-healing assay was used to detect endothelial cell migration. The expression levels of CD8 and AT2 in human nonsyndromic TAA tissues were significantly higher than those of the control. TAA tissues have more CD8+AT2+ lymphocytes than the controls. Furthermore, circulating CD8+AT2+ lymphocytes were significantly elevated in TAA patients. The expression levels of IL-2 and IFN-r in CD8+AT2+ lymphocytes were significantly increased compared with those in CD8+AT2- lymphocytes. The CD8+AT2+ lymphocytes had a greater inhibitory effect on endothelial migration compared with CD8+AT2- cells. Our findings showed that the increment of CD8+AT2+ lymphocytes in human TAA exhibited a protective effect by downregulating the release of pro-inflammation cytokines and the inhibition of endothelial cell migration.

Fisetin regulates astrocyte migration and proliferation in vitro.

Fisetin (3,3',4',7-tetrahydroxyflavone) is a plant flavonol found in fruits and vegetables that has been reported to inhibit migration and proliferation in several types of cancer. Reactive astrogliosis involves astrocyte migration and proliferation, and contributes to the formation of glial scars in central nervous system (CNS) disorders. However, the effect of fisetin on the migration and proliferation of astrocytes remains unclear. In this study, we found that fisetin inhibited astrocyte migration in a scratch-wound assay and diminished the phosphorylation of focal adhesion kinase (FAK; Tyr576/577 and paxillin (Tyr118). It also suppressed cell proliferation, as indicated by the decreased number of 5-ethynyl-2'-deoxyuridine (EdU)-positive cells, induced cell cycle arrest in the G1 phase, reduced the percentage of cells in the G2 and S phase (as measured by flow cytometry), and decreased cyclin D1 expression, but had no effect on apoptosis. Fisetin also decreased the phosphorylation levels of Akt and extracellular signal-regulated kinase (Erk)1/2, but had no effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK). These results indicate that fisetin inhibits aggressive cell phenotypes by suppressing cell migration and proliferation via the Akt/Erk signaling pathway. Fisetin may thus have potential for use as a therapeutic strategy targeting reactive astrocytes, which may lead to the inhibition of glial scar formation in vitro.

Use of human aortic extracellular matrix as a scaffold for construction of a patient-specific tissue engineered vascular patch.

Synthetic or biologic materials are usually used to repair vascular malformation in congenital heart defects; however, non-autologous materials show both mismatch compliance and antigenicity, as well as a lack of recellularization on its surface. Here, we constructed a tissue-engineered vascular patch (TEVP) using decellularized extracellular matrix (ECM) scaffold obtained from excised human aorta during surgery, which was seeded with patient-derived bone marrow CD34-positive (CD34+) progenitor cells. While cellular components were removed, the decellularized ECM scaffold retained native ECM composition, similar mechanical performance to undecellularized aortic tissue, and supported the adhesion, survival and proliferation of CD34+ progenitor cells. Interestingly, after in vitro seeding of decellularized aortic ECM scaffold for 21 d, CD34+ progenitor cells differentiated into mature vascular endothelial cells without addition of any growth factors, as confirmed by the increased levels of endothelial surface markers (CD31, Von Willebrand factor (VWF), VE-cadherin and ICAM-2) and upregulated gene levels (CD31, VWF and eNOS) concurrently with decreased expression of stem cell markers (CD133 and CD34), thus, resulting in surface endothelialization of decellularized ECM scaffold. Consequently, the patient-specific TEVP constructed in this study holds great potential for clinical use in pediatric patients with vascular malformation.

c-kit(+)AT2R(+) Bone Marrow Mononuclear Cell Subset Is a Superior Subset for Cardiac Protection after Myocardial Infarction.

Although the bone marrow mononuclear cell (BMMNC) is known as an ideal cell type for cell-based therapy for MI treatment, the effective subpopulation still remains unknown. Our study aimed at identifying the optimal subset of BMMNCs suited for cardiac regeneration. In this study, we observed that MI led to (i) a significant increase of the c-kit(+)AT2R(+) BMMNC subpopulation in mice and (ii) a modest increase of AT2R(+) BMMNCs in humans. c-kit(+)AT2R(+) and c-kit(+)AT2R(-) BMMNC subpopulations were obtained from mice after MI. Then, we cocultured cardiac H9C2 cells with c-kit(+)AT2R(+), c-kit(+)AT2R(-), and unfractionated BMMNCs; finally, we found that the c-kit(+)AT2R(+) subset is superior to the c-kit(+)AT2R(-) subset in improving cardiomyocyte protection in vitro. Of note, c-kit(+)AT2R(+) BMMNCs showed a more robust migration capacity than c-kit(+)AT2R(-) and unfractionated BMMNCs in vitro and in vivo. Additionally, compared to c-kit(+)AT2R(-) and unfractionated BMMNCs, intravenous transplantation of c-kit(+)AT2R(+) BMMNC resulted in smaller infarct size and lower levels of inflammatory reactions in heart tissue, leading to a higher global heart function improvement. In conclusion, our results indicate that the c-kit(+)AT2R(+) BMMNC subpopulation exerts a protective effect against MI and shows promising therapeutic possibilities with regard to the treatment of ischemic heart disease.