Publications by authors named "Chengming Fan"

60 Publications

Exosomes in atrial fibrillation: therapeutic potential and role as clinical biomarkers.

Heart Fail Rev 2021 Jul 12. Epub 2021 Jul 12.

Department of Cardiovascular Surgery, the Second Xiangya Hospital, Central South University, Middle Renmin Road 139, Changsha, 410011, China.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is a global epidemic. AF can cause heart failure and myocardial infarction and increase the risk of stroke, disability, and thromboembolic events. AF is becoming increasingly ubiquitous and is associated with increased morbidity and mortality at higher ages, resulting in an increasing threat to human health as well as substantial medical and social costs. Currently, treatment strategies for AF focus on controlling heart rate and rhythm with medications to restore and maintain sinus rhythm, but this approach has limitations. Catheter ablation is not entirely satisfactory and does not address the issues underlying AF. Research exploring the mechanisms causing AF is urgently needed for improved prevention, diagnosis, and treatment of AF. Exosomes are small vesicles (30-150 nm) released by cells that transmit information between cells. MicroRNAs in exosomes play an important role in the pathogenesis of AF and are established as a biomarker for AF. In this review, a summary of the role of exosomes in AF is presented. The role of exosomes and microRNAs in AF occurrence, their therapeutic potential, and their potential role as clinical biomarkers is considered. A better understanding of exosomes has the potential to improve the prognosis of AF patients worldwide, reducing the global medical burden of this disease.
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http://dx.doi.org/10.1007/s10741-021-10142-5DOI Listing
July 2021

Cell Death and Exosomes Regulation After Myocardial Infarction and Ischemia-Reperfusion.

Front Cell Dev Biol 2021 9;9:673677. Epub 2021 Jun 9.

Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.

Cardiovascular disease (CVD) is the leading cause of death in the global population, accounting for about one-third of all deaths each year. Notably, with CVDs, myocardial damages result from myocardial infarction (MI) or cardiac arrhythmias caused by interrupted blood flow. Significantly, in the process of MI or myocardial ischemic-reperfusion (I/R) injury, both regulated and non-regulated cell death methods are involved. The critical factor for patients' prognosis is the infarct area's size, which determines the myocardial cells' survival. Cell therapy for MI has been a research hotspot in recent years; however, exosomes secreted by cells have attracted much attention following shortcomings concerning immunogens. Exosomes are extracellular vesicles containing several biologically active substances such as lipids, nucleic acids, and proteins. New evidence suggests that exosomes play a crucial role in regulating cell death after MI as exosomes of various stem cells can participate in the cell damage process after MI. Hence, in the review herein, we focused on introducing various cell-derived exosomes to reduce cell death after MI by regulating the cell death pathway to understand myocardial repair mechanisms better and provide a reference for clinical treatment.
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http://dx.doi.org/10.3389/fcell.2021.673677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220218PMC
June 2021

TMSB4 Overexpression Enhances the Potency of Marrow Mesenchymal Stromal Cells for Myocardial Repair.

Front Cell Dev Biol 2021 9;9:670913. Epub 2021 Jun 9.

Department of the Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.

Objective: The actin-sequestering proteins, thymosin beta-4 (Tβ4) and hypoxia-inducible factor (HIF)-1α, are known to be associated with angiogenesis after myocardial infarction (MI). Herein, we aimed to identify the mechanism of HIF-1α induction by Tβ4 and investigate the effects of bone marrow mesenchymal stromal cells (BMMSCs) transfected with the Tβ4 gene () in a rat model of MI.

Methods: Rat BMMSCs were isolated, cultured, and transfected with the gene by using the lentivirus-mediated method. Rats with surgically induced MI were randomly divided into three groups ( = 9/group); after 1 week, the rats were injected at the heart infarcted border zone with TMSB4-overexpressed BMMSCs (BMMSC-TMSB4 ), wild-type BMMSCs that expressed normal levels of TMSB4 (BMMSC-TMSB4 ), or medium (MI). The fourth group of animals ( = 9) underwent all surgical procedures necessary for MI induction except for the ligation step (Sham). Four weeks after the injection, heart function was measured using transthoracic echocardiography. Infarct size was calculated by TTC staining, and collagen volume was measured by Masson staining. Angiogenesis in the infarcted heart area was evaluated by CD31 immunofluorescence histochemistry. experiments were carried out to observe the effect of exogenous Tβ4 on HIF-1α and explore the various possible mechanism(s).

Results: experiments showed that vascular density 4 weeks after treatment was about twofold higher in BMMSC-TMSB4 -treated animals than in BMMSC-TMSB4 -treated animals ( < 0.05). The cardiac function and infarct size significantly improved in both cell-treatment groups compared to controls. Notably, the cardiac function and infarct size were most prominent in BMMSC-TMSB4 -treated animals (both < 0.05). HIF-1α and phosphorylated HIF-1α (p-HIF-1α) were significantly enhanced by exogenous Tβ4, which was nonetheless blocked by the factor-inhibiting HIF (FIH) promoter (YC-1). The expression of prolyl hydroxylase domain proteins (PHD) was decreased upon treatment with Tβ4 and further decreased with the combined treatment of Tβ4 and FG-4497 (a specific PHD inhibitor).

Conclusion: TMSB4-transfected BMMSCs might significantly improve recovery from myocardial ischemia and promote the generation of HIF-1α and p-HIF-1α the AKT pathway, and inhibit the degradation of HIF-1α the PHD and FIH pathways.
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http://dx.doi.org/10.3389/fcell.2021.670913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221609PMC
June 2021

Case Report: Giant Biatrial Myxoma Mimicking Malignant Cardiac Tumor in a Patient With a Hepatic Angiomatous Mass.

Front Cardiovasc Med 2021 28;8:676807. Epub 2021 May 28.

Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.

Cardiac myxomas, primarily originating from the left atrium, are the most prevalent types of benign cardiac tumors; however, biatrial myxomas are extremely rare. Herein, we present a rare case of a 55-year old male with exertional dyspnea and intermittent chest discomfort due to a giant biatrial mass with concomitant atrial fibrillation and hepatic hemangioma. The giant tumor with its peduncle at the interatrial septum involved both atria; however, bulging through the tricuspid valve to the right ventricle during systole. Hence, excision of the giant cardiac tumor (which grossly composed of three parts: stiff, fleshy, and soft) and Cox-Maze IV procedure was performed with the resected specimen measuring 100 × 80 × 40 mm. The patient who was in a stable condition was discharged home on the 12th post-operative day. Thus, given the excellent post-operative results achieved, surgical treatment in large multi-cavitary benign cardiac tumors is feasible and should be considered a potentially curative therapy.
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http://dx.doi.org/10.3389/fcvm.2021.676807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192690PMC
May 2021

Visualization and Identification of Bioorthogonally Labeled Exosome Proteins Following Systemic Administration in Mice.

Front Cell Dev Biol 2021 7;9:657456. Epub 2021 Apr 7.

Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, United States.

Exosomes transport biologically active cargo (e.g., proteins and microRNA) between cells, including many of the paracrine factors that mediate the beneficial effects associated with stem-cell therapy. Stem cell derived exosomes, in particular mesenchymal stem cells (MSCs), have been shown previously to largely replicate the therapeutic activity associated with the cells themselves, which suggests that exosomes may be a useful cell-free alternative for the treatment of cardiovascular disorders. However, the mechanisms that govern how exosomes home to damaged cells and tissues or the uptake and distribution of exosomal cargo are poorly characterized, because techniques for distinguishing between exosomal proteins and proteins in the targeted tissues are lacking. Here, we report the development of an model that enabled the visualization, tracking, and quantification of proteins from systemically administered MSC exosomes. The model uses bioorthogonal chemistry and cell-selective metabolic labeling to incorporate the non-canonical amino acid azidonorleucine (ANL) into the MSC proteome. ANL incorporation is facilitated via expression of a mutant (L274G) methionyl-tRNA-synthetase (MetRS) and subsequent incubation with ANL-supplemented media; after which ANL can be covalently linked to alkyne-conjugated reagents (e.g., dyes and resins) via click chemistry. Our results demonstrate that when the exosomes produced by ANL-treated, MetRS-expressing MSCs were systemically administered to mice, the ANL-labeled exosomal proteins could be accurately and reliably identified, isolated, and quantified from a variety of mouse organs, and that myocardial infarction (MI) both increased the abundance of exosomal proteins and redistributed a number of them from the membrane fraction of intact hearts to the cytosol of cells in infarcted hearts. Additionally, we found that Desmoglein-1c is enriched in MSC exosomes and taken up by ischemic myocardium. Collectively, our results indicate that this newly developed bioorthogonal system can provide crucial insights into exosome homing, as well as the uptake and biodistribution of exosomal proteins.
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http://dx.doi.org/10.3389/fcell.2021.657456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058422PMC
April 2021

Surgical Management of a Giant Left Sinus of Valsalva Aneurysm with Coronary Artery Abnormality.

Heart Surg Forum 2021 03 25;24(2):E296-E298. Epub 2021 Mar 25.

Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.

Coronary insufficiency caused by unruptured left sinus of Valsalva aneurysm (SVA) is exceedingly rare in the literature. Herein, we present a successful surgically treated case of giant left SVA with severe aortic regurgitation and coronary insufficiency, thus introducing a tailored valve-sparing aortic root repair technique.
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http://dx.doi.org/10.1532/hsf.3643DOI Listing
March 2021

A large congenital atrial septal defect in an adult with delayed therapy.

J Int Med Res 2021 Mar;49(3):300060521997700

Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.

Patients with a large congenital atrial septal defect (ASD) traditionally have the ASD repaired at the preschool age. Unfortunately, insufficient education of patients regarding medical science and clinical recommendations can lead to delayed therapy, resulting in complications during adulthood. We report a rare case of a large congenital ASD in a 20-year-old man. Echocardiography showed a 67-mm ostium secundum defect and moderate mitral and tricuspid regurgitation. The patient underwent transthoracic ASD repair along with mitral and tricuspid valvuloplasty. This report emphasizes the importance of educating patients about congenital malformations and potential interventions in developing countries, particularly in rural communities.
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http://dx.doi.org/10.1177/0300060521997700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952845PMC
March 2021

Overexpression of the Transcription Factor Significantly Improved the Lipid Content of .

Front Bioeng Biotechnol 2021 17;9:626162. Epub 2021 Feb 17.

State Key Laboratory of Plant Cell and Chromosome Engineering, Institute of Genetics and Developmental Biology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Beijing, China.

Microalgae are considered to be a highly promising source for the production of biodiesel. However, the regulatory mechanism governing lipid biosynthesis has not been fully elucidated to date, and the improvement of lipid accumulation in microalgae is essential for the effective production of biodiesel. In this study, from , a transcription factor (TF) that affects lipid content, was transferred into . Compared with wild-type (WT) strains, the total fatty acid content and total lipid content of transgenic strains were significantly increased by 24.20-32.65 and 22.14-29.91%, respectively, under mixotrophic culture conditions and increased by 24.4-28.87 and 21.69-30.45%, respectively, under autotrophic conditions, while the protein content of the transgenic strains was significantly decreased by 18.23-21.44 and 12.28-18.66%, respectively, under mixotrophic and autotrophic conditions. Fortunately, the lipid and protein content variation did not affect the growth rate and biomass of transgenic strains under the two culture conditions. According to the transcriptomic data, the expression of 924 genes was significantly changed in the transgenic strain (LEC1-1). Of the 924 genes, 360 were upregulated, and 564 were downregulated. Based on qRT-PCR results, the expression profiles of key genes in the lipid synthesis pathway, such as , , , and , were significantly changed. By comparing the differentially expressed genes (DEGs) regulated by in and , we observed that approximately 59% (95/160) of the genes related to lipid metabolism were upregulated in transgenic . Our research provides a means of increasing lipid content by introducing exogenous TF and presents a possible mechanism of regulation of lipid accumulation in .
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http://dx.doi.org/10.3389/fbioe.2021.626162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925920PMC
February 2021

Individualized Surgical Reconstruction of the Right Ventricle Outflow Tract in Double Outlet Right Ventricle With Mirror Image-Dextrocardia.

Front Pediatr 2021 19;9:611007. Epub 2021 Feb 19.

Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.

The purpose of this study was to report our experience in the surgical reconstruction of the right ventricular outflow tract in double outlet right ventricle with a major coronary artery crossing the right ventricular outflow tract in the presence of mirror image-dextrocardia. From January 2005 to December 2019, 19 double outlet right ventricle patients (median age 4 years) with mirror image-dextrocardia and a major coronary artery crossing the right ventricular outflow tract received surgical repair. An autologous pericardial patch was used to enlarge the right ventricular outflow tract in four patients without pulmonary stenosis and three patients with mild pulmonary stenosis. A valved bovine jugular venous conduit was added to a hypoplastic native pathway in nine patients, among which six patients with moderate pulmonary stenosis received small-sized bovine jugular venous conduit implantation (diameter ≤ 16 mm). In comparison, a large-sized bovine jugular venous conduit (diameter >16 mm) was adopted in a total of three patients with severe pulmonary stenosis. Finally, three patients with preoperative pulmonary hypertension (mean pulmonary artery pressure ≥40 mmHg) did not undergo further intervention of right ventricular outflow tract due to the adequate outflow tract blood flow. There was no hospital mortality. One patient with sub-pulmonary ventricular septal defect and concomitant severe pulmonary hypertension died from respiratory failure 11 months after the operation. Kaplan-Meier survival was 94% at 5, 10 years. Within a mean echocardiographic follow-up of 6.9 ± 3.6 years, a total of two patients received reintervention due to valvular stenosis of the bovine jugular venous conduit (pressure gradient > 50 mmHg at 4 and 9 years) after surgical operation. Actuarial freedom from reoperation was 90 and 72% at 5 and 10 years, respectively. During the last echocardiographic follow-up phase, all the survivors were in NYHA class I. Double outlet right ventricle with mirror image-dextrocardia is a rare and complicated congenital cardiac malformation. Surgical reconstruction of the right ventricular outflow tract should be individualized based on the degree of pulmonary stenosis and the specific anatomical features of each patient. Reconstructing the pulmonary artery using the various sizes of valved bovine jugular venous conduit is a safe and effective surgical method.
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http://dx.doi.org/10.3389/fped.2021.611007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933223PMC
February 2021

Genome evolution during bread wheat formation unveiled by the distribution dynamics of SSR sequences on chromosomes using FISH.

BMC Genomics 2021 Jan 14;22(1):55. Epub 2021 Jan 14.

State Key Laboratory of Plant Cell and Chromosome Engineering, Institute of Genetics and Developmental Biology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Beijing, 100101, China.

Background: During the bread wheat speciation by polyploidization, a series of genome rearrangement and sequence recombination occurred. Simple sequence repeat (SSR) sequences, predominately located in heterochromatic regions of chromosomes, are the effective marker for tracing the genomic DNA sequence variations. However, to date the distribution dynamics of SSRs on chromosomes of bread wheat and its donors, including diploid and tetraploid Triticum urartu, Aegilops speltoides, Aegilops tauschii, Triticum turgidum ssp. dicocoides, reflecting the genome evolution events during bread wheat formation had not been comprehensively investigated.

Results: The genome evolution was studied by comprehensively comparing the distribution patterns of (AAC), (AAG), (AGC) and (AG) in bread wheat Triticum aestivum var. Chinese Spring and its progenitors T. urartu, A. speltoides, Ae. tauschii, wild tetroploid emmer wheat T. dicocoides, and cultivated emmer wheat T. dicoccum. Results indicated that there are specific distribution patterns in different chromosomes from different species for each SSRs. They provided efficient visible markers for identification of some individual chromosomes and SSR sequence evolution tracing from the diploid progenitors to hexaploid wheat. During wheat speciation, the SSR sequence expansion occurred predominately in the centromeric and pericentromeric regions of B genome chromosomes accompanied by little expansion and elimination on other chromosomes. This result indicated that the B genome might be more sensitive to the "genome shock" and more changeable during wheat polyplodization.

Conclusions: During the bread wheat evolution, SSRs including (AAC), (AAG), (AGC) and (AG) in B genome displayed the greatest changes (sequence expansion) especially in centromeric and pericentromeric regions during the polyploidization from Ae. speltoides S genome, the most likely donor of B genome. This work would enable a better understanding of the wheat genome formation and evolution and reinforce the viewpoint that B genome was originated from S genome.
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http://dx.doi.org/10.1186/s12864-020-07364-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809806PMC
January 2021

Subtotal Resection for the Symptom Relief of a Fatal and Aggressive Primary Cardiac Liposarcoma: A Case Report.

Heart Surg Forum 2020 Nov 23;23(6):E867-E869. Epub 2020 Nov 23.

Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.

Primary cardiac liposarcoma is a rare malignant soft tissue lesion, but there are still no diagnosis and treatment guidelines for this disease. This is the case report of a 59-year-old male with cardiac liposarcoma infiltrating the mitral valve and the left atrium. He achieved satisfactory symptom relief with subtotal resection.
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http://dx.doi.org/10.1532/hsf.3193DOI Listing
November 2020

Spatial Divergence of Modules Maintains Phosphorus Homeostasis in Soybean Nodules.

Plant Physiol 2020 09 17;184(1):236-250. Epub 2020 Jul 17.

Ministry of Agriculture and Rural Affairs of the People's Republic of China Key Laboratory of Soybean Biology (Beijing), National Key Facility of Crop Gene Resource and Genetic Improvement, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, 100081 Beijing, China

Maintaining phosphorus (Pi) homeostasis in nodules is the key to nodule development and nitrogen fixation, an important source of nitrogen for agriculture and ecosystems. () and its regulator (), which constitute the module, play important roles in maintaining Pi homeostasis in different organs. However, the module and its functions in nodules remain unknown. We identified one () and four () homologs in soybean () plants, which displayed specific expression patterns in different tissues in nodules, similar to previously reported and Through the integration of different approaches, modules were confirmed. Combining our results and previous reports, we established multiple modules acting in the infected or noninfected tissues in nodules. A single had more than one target, and vice versa. Therefore, overlapping and cross-talking modules monitored the wave of available Pi to maintain Pi homeostasis in nodules, which sequentially regulated nodule initiation and development. High levels of enhanced Pi accumulation in nodules, increased nodule size, but decreased nodule number. Nitrogenase activity was also enhanced by Our findings uncover modules in nodules, which expands our understanding of the mechanism of maintaining Pi homeostasis in soybean plants.
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http://dx.doi.org/10.1104/pp.19.01209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479890PMC
September 2020

Nanoparticle-Mediated Drug Delivery for Treatment of Ischemic Heart Disease.

Front Bioeng Biotechnol 2020 24;8:687. Epub 2020 Jun 24.

Department of Cardiovascular Diseases, Mayo Clinic, Scottsdale, AZ, United States.

The regenerative capacity of an adult cardiac tissue is insufficient to repair the massive loss of heart tissue, particularly cardiomyocytes (CMs), following ischemia or other catastrophic myocardial injuries. The delivery methods of therapeutics agents, such as small molecules, growth factors, exosomes, cells, and engineered tissues have significantly advanced in medical science. Furthermore, with the controlled release characteristics, nanoparticle (NP) systems carrying drugs are promising in enhancing the cardioprotective potential of drugs in patients with cardiac ischemic events. NPs can provide sustained exposure precisely to the infarcted heart via direct intramyocardial injection or intravenous injection with active targets. In this review, we present the recent advances and challenges of different types of NPs loaded with agents for the repair of myocardial infarcted heart tissue.
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http://dx.doi.org/10.3389/fbioe.2020.00687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326780PMC
June 2020

Application of Modified Sliding Anastomosis in the Repair of Aortic Coarctation.

Biomed Res Int 2020 14;2020:3805385. Epub 2020 May 14.

Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Middle Renmin Road 139, Changsha 410000, China.

Objectives: To evaluate the early and midterm results of a modified sliding anastomosis technique in patients with aortic coarctation.

Materials And Methods: In this study, we reported a new repair method and compared the early and midterm outcome(s) with a conventional surgical approach for the management of patients with aortic coarctation. Forty-eight aortic coarctation patients with a narrowed segment length longer than 2 cm were operated at our department's pediatric surgical division. Excision of the coarctation and end-to-end anastomosis was carried out in twenty-five patients (control group). In contrast, a modified sliding technique was used for twenty-three cases in the observation group. Other accompanying cardiac anomalies simultaneously repaired included ventricular septal defect and patent ductus arteriosus. All patients received 1.5-10 years of postoperative echocardiographic follow-up.

Results: This is a retrospective study carried out between January 2005 and June 2018. The study population consisted of forty-eight patients, which included twenty-six male and twenty-two female patients, with an average age of 5.2 ± 1.9 months (range, 28 days to 1 year). There was no mortality. The operative time, the number of intercostal artery disconnection, the drainage volume, and arm-leg systolic pressure gradient postoperation were less in the observation group as compared to the control group ( < 0.05). Also, cases with an anastomotic pressure gradient exceeding 10 mmHg during follow-up were less in the observation group as compared to the control group ( < 0.05). The postoperative complications encountered were chylothorax (control group 2 cases vs. observation group 0) and pulmonary atelectasis (control group 4 cases vs. observation group 1). They all, however, recovered after conservative treatment. Three patients in the control group underwent balloon angioplasty (reintervention) postoperative 2-4 years due to an increase in the anastomotic pressure gradient (>20 mmHg). After reintervention, the anastomotic pressure gradient reduced to 14 mmHg, 15 mmHg, and 17 mmHg, respectively.

Conclusions: For long segment aortic coarctation patients (longer than 2 cm), the use of the modified sliding anastomotic technique effectively helps to retain more autologous tissues, enlarge the diameter of the anastomosis, and decrease anastomotic tension and vascular injury. Therefore, this technique provides a new idea for the surgical treatment of aortic coarctations.
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http://dx.doi.org/10.1155/2020/3805385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245663PMC
March 2021

Myocardial protection by nanomaterials formulated with CHIR99021 and FGF1.

JCI Insight 2020 06 18;5(12). Epub 2020 Jun 18.

Department of Biomedical Engineering, School of Medicine, and School of Engineering, the University of Alabama at Birmingham, Birmingham, Alabama, USA.

The mortality of patients suffering from acute myocardial infarction is linearly related to the infarct size. As regeneration of cardiomyocytes from cardiac progenitor cells is minimal in the mammalian adult heart, we have explored a new therapeutic approach, which leverages the capacity of nanomaterials to release chemicals over time to promote myocardial protection and infarct size reduction. Initial screening identified 2 chemicals, FGF1 and CHIR99021 (a Wnt1 agonist/GSK-3β antagonist), which synergistically enhance cardiomyocyte cell cycle in vitro. Poly-lactic-co-glycolic acid nanoparticles (NPs) formulated with CHIR99021 and FGF1 (CHIR + FGF1-NPs) provided an effective slow-release system for up to 4 weeks. Intramyocardial injection of CHIR + FGF1-NPs enabled myocardial protection via reducing infarct size by 20%-30% in mouse or pig models of postinfarction left ventricular (LV) remodeling. This LV structural improvement was accompanied by preservation of cardiac contractile function. Further investigation revealed that CHIR + FGF1-NPs resulted in a reduction of cardiomyocyte apoptosis and increase of angiogenesis. Thus, using a combination of chemicals and an NP-based prolonged-release system that works synergistically, this study demonstrates a potentially novel therapy for LV infarct size reduction in hearts with acute myocardial infarction.
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http://dx.doi.org/10.1172/jci.insight.132796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406256PMC
June 2020

CHIR99021 and fibroblast growth factor 1 enhance the regenerative potency of human cardiac muscle patch after myocardial infarction in mice.

J Mol Cell Cardiol 2020 04 10;141:1-10. Epub 2020 Mar 10.

Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address:

Background: We have shown that genetic overexpression of cell cycle proteins can increase the proliferation of transplanted cardiomyocytes derived from human induced-pluripotent stem cells (hiPSC-CMs) in animal models of myocardial infarction (MI). Here, we introduce a new, non-genetic approach to promote hiPSC-CM cell cycle activity and proliferation in transplanted human cardiomyocyte patches (hCMPs).

Methods: Mice were randomly distributed into 5 experimental groups (n = 10 per group). One group underwent Sham surgery, and the other 4 groups underwent MI induction surgery followed by treatment with hCMPs composed of hiPSC-CMs and nanoparticles that contained CHIR99021 and FGF1 (the NP-hCMP group), with hCMPs composed of hiPSC-CMs and empty nanoparticles (the NP-hCMP group); with patches containing the CHIR99021/FGF-loaded nanoparticles but lacking hiPSC-CMs (the NP-Patch group), or patches lacking both the nanoparticles and cells (the E-Patch group). Cell cycle activity was evaluated via Ki67 and Aurora B expression, bromodeoxyuridine incorporation, and phosphorylated histone 3 levels (immunofluorescence); engraftment via human cardiac troponin T or human nuclear antigen expression (immunofluorescence) and bioluminescence imaging; cardiac function via echocardiography; infarct size and wall thickness via histology; angiogenesis via isolectin B4 expression (immunofluorescence); and apoptosis via TUNEL and caspace 3 expression (immunofluorescence).

Results: Combined CHIR99021- and FGF1-treatment significantly increased hiPSC-CM cell cycle activity both in cultured cells (by 4- to 6-fold) and in transplanted hCMPs, and compared to treatment with NP-hCMPs, NP-hCMP transplantation increased hiPSC-CM engraftment by ~4-fold and was associated with significantly better measurements of cardiac function, infarct size, wall thickness, angiogenesis, and hiPSC-CM apoptosis four weeks after MI induction.

Conclusions: Nanoparticle-mediated CHIR99021 and FGF1 delivery promotes hiPSC-CM cell cycle activity and proliferation, as well as the engraftment and regenerative potency of transplanted hCMPs, in a mouse MI model.
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http://dx.doi.org/10.1016/j.yjmcc.2020.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304478PMC
April 2020

Utilization of Human Induced Pluripotent Stem Cells for Cardiac Repair.

Front Cell Dev Biol 2020 31;8:36. Epub 2020 Jan 31.

Department of Cardiovascular Medicine, Physiology and Biomedical Engineering, Mayo Clinic, Scottsdale, AZ, United States.

The paracrine effect, mediated by chemical signals that induce a physiological response on neighboring cells in the same tissue, is an important regenerative mechanism for stem cell-based therapy. Exosomes are cell-secreted nanovesicles (50-120 nm) of endosomal origin, and have been demonstrated to be a major contributor to the observed stem cell-mediated paracrine effect in the cardiac repair process. Following cardiac injury, exosomes deriving from exogenous stem cells have been shown to regulate cell apoptosis, proliferation, angiogenesis, and fibrosis in the infarcted heart. Exosomes also play a crucial role in the intercellular communication between donor and recipient cells. Human induced pluripotent stem cells (hiPSCs) are promising cell sources for autologous cell therapy in regenerative medicine. Here, we review recent advances in the field of progenitor-cell derived, exosome-based cardiac repair, with special emphasis on exosomes derived from hiPSCs.
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http://dx.doi.org/10.3389/fcell.2020.00036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025514PMC
January 2020

Cardiomyocytes from CCND2-overexpressing human induced-pluripotent stem cells repopulate the myocardial scar in mice: A 6-month study.

J Mol Cell Cardiol 2019 12 17;137:25-33. Epub 2019 Oct 17.

Department of Biomedical Engineering, School of Medicine, School of Engineering, University of Alabama at Birmingham, USA. Electronic address:

Background: Cardiomyocytes that have been differentiated from CCND2-overexpressing human induced-pluripotent stem cells (hiPSC-CCND2 CMs) can proliferate when transplanted into mouse hearts after myocardial infarction (MI). However, it is unknown whether remuscularization can replace the thin LV scar and if the large muscle graft can electrophysiologically synchronize to the recipient myocardium. Our objectives are to evaluate the structural and functional potential of hiPSC-CCND2 CMs in replacing the LV thin scar.

Methods: NOD/SCID mice were treated with hiPSC-CCND2 CMs (i.e., the CCND2 group), hiPSC-CCND2 CMs (the CCND2 group), or an equal volume of PBS immediately after experimentally-induced myocardial infarction. The treatments were administered to one site in the infarcted zone (IZ), two sites in the border zone (BZ), and a fourth group of animals underwent Sham surgery.

Results: Six months later, engrafted cells occupied >50% of the scarred region in CCND2 animals, and exceeded the number of engrafted cells in CCND2 animals by ~8-fold. Engrafted cells were also more common in the IZ than in the BZ for both cell-treatment groups. Measurements of cardiac function, infarct size, wall thickness, and cardiomyocyte hypertrophy were significantly improved in CCND2 animals compared to animals from the CCND2 or PBS-treatment groups. Measurements in the CCND2 and PBS groups were similar, and markers for cell cycle activation and proliferation were significantly higher in hiPSC-CCND2 CMs than in hiPSC-CCND2 CMs. Optical mapping of action potential propagation indicated that the engrafted hiPSC-CCND2 CMs were electrically coupled to each other and to the cells of the native myocardium. No evidence of tumor formation was observed in any animals.

Conclusions: Six months after the transplantation, CCND2-overexpressing hiPSC-CMs proliferated and replaced >50% of the myocardial scar tissue. The large graft hiPSC-CCND2 CMs also electrically integrated with the host myocardium, which was accompanied by a significant improvement in LV function.
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http://dx.doi.org/10.1016/j.yjmcc.2019.09.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346870PMC
December 2019

Reabsorbable Pins can Reinforce an Early Sternal Stability After Median Sternotomy in Young Children with Congenital Heart Disease.

Pediatr Cardiol 2019 Dec 23;40(8):1728-1734. Epub 2019 Sep 23.

Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Middle Renmin Road 139, Changsha, 410011, China.

We evaluated the efficacy of bioresorbable sternal reinforcement device (poly-L-lactide sternal pins) on sternal healing after median sternotomy in young children (with body weight less than 10 kg) with congenital heart disease (CHD). Data from 85 patients, who underwent CHD surgery through median sternotomy from October 2016 to May 2018, were collected and analyzed. Sternal pins were utilized in 85 patients (10 mm × 1 mm × 1 mm for patients with body weights less than 5 kg and 15 mm × 2 mm × 2 mm for those weighing between 5 and 10 kg) in addition to sternum closure with Ethicon PDSII running sutures (Group A), while 84 patients received the Ethicon sternal closure (Group B) with no pins. The occurrence of sternal dehiscence, anterior-posterior displacement, and high-low displacement was evaluated by physical examination and three-dimensional computed tomography at one month postoperatively. No anterior-posterior sternal displacement (0%) was observed in Group A, while 10 anterior-posterior displacements (11.9%) were observed in Group B (P < 0.01). The number of sternal caudal-cranial displacements in Groups A and B was 4 (4.71%) and 5 (5.35%), respectively (P = 0.870). While no sternal dehiscence (0%) was observed in Group A, 7 out of 84 patients (8.33%) in Group B exhibited obvious sternal dehiscence (P < 0.01). The bioresorbable poly-L-lactide sternal pins reduced an anterior-posterior sternal displacement and sternal dehiscence, which was accompanied by a significant improvement of an early sternal fixation.
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http://dx.doi.org/10.1007/s00246-019-02212-1DOI Listing
December 2019

A mutated rabbit defensin NP-1 produced by Chlorella ellipsoidea can improve the growth performance of broiler chickens.

Sci Rep 2019 09 4;9(1):12778. Epub 2019 Sep 4.

State Key Laboratory of Plant Cell and Chromosome Engineering, The Innovative Academy of Seed Design, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.

The demand for alternatives to antibiotics to improve the growth performance of food animals is increasing. Defensins constitute the first line of defence against pathogens in the innate immune system of animals and humans. A transgenic Chlorella ellipsoidea strain producing mNP-1 (a mutated rabbit defensin NP-1) was previously obtained in our laboratory. In this study, a process for producing the transgenic strain on a large scale was developed, and the C. ellipsoidea strain producing mNP-1 was used as a feed additive to improve the health and growth performance of chickens. The volume of C. ellipsoidea producing mNP-1 can be scaled up to 10,000 L with approximately 100 g/L dry biomass, and the mNP-1 content of transgenic microalgal powder (TMP) was 90-105 mg/L. A TMP-to-regular feed ratio of 1‰, as the optimal effective dose, can promote the growth of broiler chickens by increasing weight by 9.27-12.95%. mNP-1 can improve duodenum morphology by promoting long and thin villi and affect the microbial community of the duodenum by increasing the diversity and abundance of beneficial microbes. These results suggested that transgenic Chlorella producing mNP-1 can be industrially produced and used as an effective feed additive and an alternative to antibiotics for improving the health and growth performance of broiler chickens or other types of food animals/poultry.
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http://dx.doi.org/10.1038/s41598-019-49252-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726607PMC
September 2019

Functionally Competent DNA Damage-Free Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Myocardial Repair.

Circulation 2019 08 5;140(6):520-522. Epub 2019 Aug 5.

Department of Biomedical Engineering, School of Engineering (R.K., J.F.T., J.M.M., C.F., A.G.R., N.S.R., J.Z.), School of Medicine, The University of Alabama at Birmingham.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.040881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686875PMC
August 2019

Enhancing the Engraftment of Human Induced Pluripotent Stem Cell-derived Cardiomyocytes via a Transient Inhibition of Rho Kinase Activity.

J Vis Exp 2019 07 10(149). Epub 2019 Jul 10.

Department of Biomedical Engineering, School of Medicine, School of Engineering, University of Alabama at Birmingham;

A crucial factor in improving cellular therapy effectiveness for myocardial regeneration is to safely and efficiently increase the cell engraftment rate. Y-27632 is a highly potent inhibitor of Rho-associated, coiled-coil-containing protein kinase (RhoA/ROCK) and is used to prevent dissociation-induced cell apoptosis (anoikis). We demonstrate that Y-27632 pretreatment for human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) prior to implantation results in a cell engraftment rate improvement in a mouse model of acute myocardial infarction (MI). Here, we describe a complete procedure of hiPSC-CMs differentiation, purification, and cell pretreatment with Y-27632, as well as the resulting cell contraction, calcium transient measurements, and transplantation into mouse MI models. The proposed method provides a simple, safe, effective, and low-cost method which significantly increases the cell engraftment rate. This method cannot only be used in conjunction with other methods to further enhance the cell transplantation efficiency but also provides a favorable basis for the study of the mechanisms of other cardiac diseases.
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http://dx.doi.org/10.3791/59452DOI Listing
July 2019

N-cadherin overexpression enhances the reparative potency of human-induced pluripotent stem cell-derived cardiac myocytes in infarcted mouse hearts.

Cardiovasc Res 2020 03;116(3):671-685

Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, 1670 University Boulevard, Volker Hall G094J, Birmingham, AL 35294, USA.

Aims: In regenerative medicine, cellular cardiomyoplasty is one of the promising options for treating myocardial infarction (MI); however, the efficacy of such treatment has shown to be limited due to poor survival and/or functional integration of implanted cells. Within the heart, the adhesion between cardiac myocytes (CMs) is mediated by N-cadherin (CDH2) and is critical for the heart to function as an electromechanical syncytium. In this study, we have investigated whether the reparative potency of human-induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs) can be enhanced through CDH2 overexpression.

Methods And Results: CDH2-hiPSC-CMs and control wild-type (WT)-hiPSC-CMs were cultured in myogenic differentiation medium for 28 days. Using a mouse MI model, the cell survival/engraftment rate, infarct size, and cardiac functions were evaluated post-MI, at Day 7 or Day 28. In vitro, conduction velocities were significantly greater in CDH2-hiPSC-CMs than in WT-hiPSC-CMs. While, in vivo, measurements of cardiac functions: left ventricular (LV) ejection fraction, reduction in infarct size, and the cell engraftment rate were significantly higher in CDH2-hiPSC-CMs treated MI group than in WT-hiPSC-CMs treated MI group. Mechanistically, paracrine activation of ERK signal transduction pathway by CDH2-hiPSC-CMs, significantly induced neo-vasculogenesis, resulting in a higher survival of implanted cells.

Conclusion: Collectively, these data suggest that CDH2 overexpression enhances not only the survival/engraftment of cultured CDH2-hiPSC-CMs, but also the functional integration of these cells, consequently, the augmentation of the reparative properties of implanted CDH2-hiPSC-CMs in the failing hearts.
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http://dx.doi.org/10.1093/cvr/cvz179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204485PMC
March 2020

Clinical Study to Individual Treatment for Major Aortopulmonary Collaterals of Tetralogy of Fallot.

Biomed Res Int 2019 15;2019:1603712. Epub 2019 May 15.

Department of the Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Middle Renmin Road 139, 410011 Changsha, China.

Objectives: To build a guideline for the individual treatment of Tetralogy of Fallot (TOF) with major aortopulmonary collaterals (MAPCAs) and tentatively establish the occlusion index of MAPCAs.

Methods: According to the diameter of the aortopulmonary collaterals (R: mm) and the bodyweight of the children (weight: kg), K= ((∑ )/) was set as the occlusion index of TOF with MAPCAs. A retrospective study was initially performed in 171 patients who suffered from TOF with MAPCAs and underwent cardiac malformation repair to investigate the intervals of the K value: K≥2, 1
Result: The proportion of the patients treated with occlusion and the postoperative ICU resident time (p<0.05) in patients with 1
Conclusion: Due to restrictions on medical conditions in China with a large population base, a standard individual treatment of TOF with MAPCAs should be established based on the Aortopulmonary Collaterals Occlusion Index K= ((∑ )/), which can effectively avoid unnecessary collateral occlusion, minimize trauma, and shorten the length of ICU and hospital stay. When K≥2, the collateral occlusion and surgical correction are recommended to be performed simultaneously. When 1
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http://dx.doi.org/10.1155/2019/1603712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541992PMC
December 2019

In silico genome-wide identification and comprehensive characterization of the gene family in soybean.

Heliyon 2019 Jun 9;5(6):e01868. Epub 2019 Jun 9.

Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.

The transcription factor family play a central role in brassinosteroid signaling pathway that regulates a wide range of plant growth and developmental processes, as well as resistances to various stresses. However, no comprehensive study of the gene family in soybean has been reported. In this work, 16 -like genes were identified in soybean, which could be divided into two clades based on their phylogenetic relationships, gene structures and motif compositions. We then examined their duplication status and evolutionary models. The result showed that most of the -like genes have duplicated counterparts generated from the recent Glycine WGD event, and these genes are originated from 6 distinct ancestors before the Gamma WGT event. We further studied the expression profiles of -like genes, and found their spatio-temporal and stressed expression patterns varied tremendously. For example, and were highly expressed in almost every sample, whereas and were not expressed. Additionally, interaction network analysis revealed the presence of 3 clusters between like genes and other associated genes, implying that they have both the conserved and divergent functions. Lastly, we analyzed the genetic diversity of like genes in 302 resequenced wild, landrace and improved soybean accessions. It showed that most of these genes are well conserved, and they are not changed during domestication and improvement. These results provide insights into the characterization of family and lay the foundation for further functional study of such genes.
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http://dx.doi.org/10.1016/j.heliyon.2019.e01868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558309PMC
June 2019

The transcription factor family in soybean: Genome-wide identification, expression profiling and genetic diversity analysis.

FEBS Open Bio 2019 04 21;9(4):629-642. Epub 2019 Feb 21.

College of Life Sciences and Oceanography Shenzhen University China.

The transcription factor family plays a critical role in the ethylene signaling pathway, which regulates a broad spectrum of plant growth and developmental processes, as well as defenses to myriad stresses. Although genome-wide analysis of this family has been carried out for several plant species, no comprehensive analysis of the gene family in soybean has been reported so far. Furthermore, there are few studies on the functions of genes in soybean. In this study, we identified 12 soybean () genes, which we divided into three groups based on their phylogenetic relationships. We then detected their duplication status and found that most of the genes have duplicated copies derived from two whole-genome duplication events. These duplicated genes underwent strong negative selection during evolution. We further analyzed the transcript profiles of genes using the transcriptome data and found that their spatio-temporal and stress expression patterns varied considerably. For example, - were found to be strongly expressed in almost every sample, while - exhibited low expression, or were not expressed at all. Additionally, these genes showed different responses to dehydration, salinity and phosphate starvation. Finally, we surveyed genetic variations of these genes in 302 resequenced wild soybeans, landraces and improved soybean cultivars. Our data showed that most genes are well conserved, and are not modified in domesticated or improved cultivars. Together, these findings provide a potentially valuable resource for characterizing the gene family and lay the basis for further elucidation of their molecular mechanisms.
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http://dx.doi.org/10.1002/2211-5463.12596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443860PMC
April 2019

Newly Identified Essential Amino Acids Affecting DGAT1 Function Revealed by Site-Directed Mutagenesis.

Int J Mol Sci 2018 Nov 4;19(11). Epub 2018 Nov 4.

State Key Laboratory of Plant Cell and Chromosome Engineering, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.

Diacylglycerol acyltransferase (DGAT) is a rate-limiting enzyme in the synthesis of triacylglycerol (TAG), the most important form of energy storage in plants. Some residues have previously been proven to be crucial for DGAT1 activity. In this study, we used site-directed mutagenesis of the gene from to alter 16 amino acids to investigate effects on DGAT1 function. Of the 16 residues (L482R, E542R, Y553A, G577R, R579D, Y582R, R596D, H603D, H609D, A624R, F629R, S632A, W650R, A651R, Q658H, and P660R), we newly identified 5 (L482, R579, H603, A651, and P660) as being essential for DGAT1 function and 7 (E542, G577, R596, H609, A624, S632, and Q658) that significantly affect DGAT1 function to different degrees, as revealed by heterologous expression of the mutants in yeast strain INVSc1. Importantly, compared with , expression of the mutant significantly increased the total fatty acid and TAG contents of INVSc1. Comparison among CeDGAT1Y553A, GmDGAT1Y341A, AtDGAT1Y364A, BnDGAT1Y347A, and BoDGAT1Y352A, in which tyrosine at the position corresponding to the 553rd residue in CeDGAT1 is changed into alanine, indicated that the impact of changing Y to A at position 553 is specific for CeDGAT1. Overall, the results provide novel insight into the structure and function of DGAT1, as well as a mutant gene with high potential for lipid improvement in microalgae and plants.
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http://dx.doi.org/10.3390/ijms19113462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274981PMC
November 2018

Y-27632 preconditioning enhances transplantation of human-induced pluripotent stem cell-derived cardiomyocytes in myocardial infarction mice.

Cardiovasc Res 2019 02;115(2):343-356

Department of Biomedical Engineering, School of Medicine, School of Engineering, University of Alabama at Birmingham, 1670 University Blvd, VH G094E, Birmingham, AL, USA.

Aims: The effectiveness of cell-based treatments for regenerative myocardial therapy is limited by low rates of cell engraftment. Y-27632 inhibits Rho-associated protein kinase (ROCK), which regulates the cytoskeletal changes associated with cell adhesion, and has been used to protect cultured cells during their passaging. Here, we investigated whether preconditioning of cardiomyocytes, derived from human-induced pluripotent stem cells (hiPSC-CM), with Y-27632 improves their survival and engraftment in a murine model of acute myocardial infarction (MI).

Methods And Results: After MI induction, mice were subjected to intramyocardial injections of phosphate-buffered saline, hiPSC-CM cultured under standard conditions (hiPSC-CM-RI), or Y-27632-preconditioned hiPSC-CM (hiPSC-CM+RI). The resulting engraftment rate calculated 4 weeks after implantation was significantly higher and the abundance of apoptotic transplanted cells was significantly lower in hiPSC-CM+RI recipients than in hiPSC-CM-RI animals. In cultured hiPSC-CM, Y-27632-preconditioning reversibly reduced contractile activity and the expression of troponin genes, while increasing their attachment to an underlying mouse cardiomyocyte (HL1) monolayer. Y-27632 preconditioning also increased the expression of N-cadherin and integrin ß1, the two cell junction proteins. hiPSC-CM+RI were also larger in cell area with greater cytoskeletal alignment and a more rod-like shape than hiPSC-CM-RI, both after transplantation (in vivo) and in culture. The effects of Y-27632 preconditioning on contractile activity and morphology of hiPSC-CMs in culture, as well as on their engraftment rate and apoptotic death in MI mouse grafts, could be recapitulated by hiPSC-CM treatment with the L-type calcium-channel blocker verapamil.

Conclusion: Preconditioning with the ROCK inhibitor Y-27632 increased the engraftment of transplanted hiPSC-CM in a murine MI model, while reversibly impairing hiPSC-CM contractility and promoting adhesion.
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http://dx.doi.org/10.1093/cvr/cvy207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341224PMC
February 2019

Regenerative Potential of Neonatal Porcine Hearts.

Circulation 2018 12;138(24):2809-2816

Department of Biomedical Engineering, School of Medicine, and School of Engineering (W.Z., E.Z., M.Z., C.F., Y.T., J.D.H., A.V.B., G.P.W., G.Q., J.Z.), University of Alabama at Birmingham.

Background: Rodent hearts can regenerate myocardium lost to apical resection or myocardial infarction for up to 7 days after birth, but whether a similar window for myocardial regeneration also exists in large mammals is unknown.

Methods: Acute myocardial infarction (AMI) was surgically induced in neonatal pigs on postnatal days 1, 2, 3, 7, and 14 (ie, the P1, P2, P3, P7, and P14 groups, respectively). Cardiac systolic function was evaluated before AMI and at 30 days post-AMI via transthoracic echocardiography. Cardiomyocyte cell cycle activity was assessed via immunostaining for proliferation and mitosis markers, infarct size was evaluated histologically, and telomerase activity was measured by quantitative polymerase chain reaction.

Results: Systolic function at day 30 post-AMI was largely restored in P1 animals and partially restored in P2 animals, but significantly impaired when AMI was induced on postnatal day 3 or later. Hearts of P1 animals showed little evidence of scar formation or wall thinning on day 30 after AMI, with increased measures of cell-cycle activity seen 6 days after AMI (ie, postnatal day 7) compared with postnatal day 7 in noninfarcted hearts.

Conclusions: The neonatal porcine heart is capable of regeneration after AMI during the first 2 days of life. This phenomenon is associated with induction of cardiomyocyte proliferation and is lost when cardiomyocytes exit the cell cycle shortly after birth.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.034886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301098PMC
December 2018

[Advances in haplotype analysis technique].

Sheng Wu Gong Cheng Xue Bao 2018 Jun;34(6):852-861

Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.

Haplotype is the combination of a series of genetic mutations that coexist on a single chromosome, each of which has its own unique haplotypes. As a common data analysis method, the analysis of haplotype is effective for the localization of heterozygosis SNPs on single chromosome, the excavation of disease genes and the search of maladies treatments. It mainly includes indirect computational inferential method and direct experimental method. In this review we introduced various haplotype analysis methods and applications, especially two important ones: single-molecule dilution and contiguity-preserving transposition sequencing common technology. Meanwhile, further research prospects on haplotype sequencing were proposed.
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http://dx.doi.org/10.13345/j.cjb.170451DOI Listing
June 2018
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