Manling Zhang

ORCID: 0000-0002-5447-2615
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About
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Research Areas
  • Phosphodiesterase function and regulation
  • Pluripotent Stem Cells Research
  • CRISPR and Genetic Engineering
  • Renal and related cancers
  • Heart Failure Treatment and Management
  • Nitric Oxide and Endothelin Effects
  • Animal Genetics and Reproduction
  • Tissue Engineering and Regenerative Medicine
  • Cardiac Fibrosis and Remodeling
  • Signaling Pathways in Disease
  • Nuclear Receptors and Signaling
  • Reproductive Biology and Fertility
  • Congenital heart defects research
  • Genetic Associations and Epidemiology
  • RNA modifications and cancer
  • Cancer-related molecular mechanisms research
  • Cancer-related gene regulation
  • Mitochondrial Function and Pathology
  • Xenotransplantation and immune response
  • Neonatal Respiratory Health Research
  • Adipose Tissue and Metabolism
  • Autonomous Vehicle Technology and Safety
  • Video Surveillance and Tracking Methods
  • Time Series Analysis and Forecasting
  • NF-κB Signaling Pathways

Inner Mongolia Medical University
2024-2025

Johns Hopkins University
2007-2024

Nanjing Medical University
2015-2024

Hefei University of Technology
2022-2024

University of Pittsburgh
2024

Johns Hopkins Medicine
2007-2024

Chinese Academy of Sciences
2023

Institute of Microbiology
2023

University of Chinese Academy of Sciences
2023

Inner Mongolia University
2019-2021

Cardiac myocyte targeted MerCreMer transgenic mice expressing tamoxifen-inducible Cre driven by the α-myosin heavy chain promoter are increasingly used to control gene expression in adult heart. Here, we show tamoxifen-mediated (MCM) nuclear translocation can induce severe transient dilated cardiomyopathy with or without loxP transgenes. The is accompanied marked reduction of energy/metabolism and calcium-handling (eg, PGC1-α, peroxisome proliferator-activated α, SERCA2A), all fully...

10.1161/circresaha.109.198416 article EN Circulation Research 2009-06-12

The heart initially compensates for hypertension-mediated pressure overload by enhancing its contractile force and developing hypertrophy without dilation. Gq protein–coupled receptor pathways become activated can depress function, leading to cardiac failure. Initial adaptation mechanisms reduce damage during such stimulation remain largely unknown. Here we have shown that this initial requires regulator of G protein signaling 2 (RGS2). Mice lacking RGS2 had a normal basal phenotype, yet...

10.1172/jci35620 article EN Journal of Clinical Investigation 2009-01-05

The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) mediated Cas9 nuclease system has been extensively used for genome editing and gene modification in eukaryotic cells. CRISPR/Cas9 technology holds great potential various applications, including the correction of genetic defects or mutations within human genome. application disease research is anticipated to solve a multitude intricate molecular biology challenges encountered life science research. Here, we review...

10.3389/fgene.2024.1364742 article EN cc-by Frontiers in Genetics 2024-04-11

Inhibition of cGMP-specific phosphodiesterase 5 (PDE5) ameliorates pathological cardiac remodeling and has been gaining attention as a potential therapy for heart failure. Despite promising results in males, the efficacy PDE5 inhibitor sildenafil female pathologies not determined might be affected by estrogen levels, given hormone's involvement cGMP synthesis. Here, we that heart-protective effect mice depends on presence via mechanism involves myocyte eNOS-dependent synthesis cGMP-dependent...

10.1172/jci70731 article EN Journal of Clinical Investigation 2014-05-15

Abstract Efficient isolation of embryonic stem (ES) cells from pre-implantation porcine embryos has remained a challenge. Here, we describe the derivation stem-like (pESLCs) by seeding isolated inner cell mass (ICM) in vitro -produced blastocyst into α-MEM with basic fibroblast growth factor (bFGF). The pESL kept normal karyotype and displayed flatten clones, similar phenotype to human (hES cells) rodent epiblast cells. These exhibited alkaline phosphatase (AP) activity expressed...

10.1038/srep25838 article EN cc-by Scientific Reports 2016-05-13

ABSTRACT Miniature pigs have advantages over rodents in modeling atherosclerosis because their cardiovascular system and physiology are similar to that of humans. Apolipoprotein E (ApoE) deficiency has long been implicated disease To establish an improved large animal model familial hypercholesterolemia atherosclerosis, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9) was used disrupt ApoE gene Bama miniature pigs. Biallelic-modified...

10.1242/dmm.036632 article EN cc-by Disease Models & Mechanisms 2018-10-01

Objectives Genome-wide association studies (GWASs) have discovered associations of numerous SNPs and genes with obesity. However, the underlying molecular mechanisms through which these affect predisposition to obesity remain not fully understood. Aims our study are comprehensively characterize GWAS computational approaches. Methods For identified SNPs, functional annotation, effects on miRNAs binding impact protein phosphorylation were performed via RegulomeDB 3DSNP, miRNASNP, PhosSNP 1.0...

10.1371/journal.pone.0199987 article EN cc-by PLoS ONE 2018-07-02

The scarcity of donor kidneys greatly impacts the survival patients with end-stage renal failure. Pigs are increasingly becoming potential organ donors but limited by immunological rejection. Based on human kidney organoid already established CHIR99021 and FGF9 induction strategy, we generated porcine organoids from naïve-like ESCs (nESCs). derived had a tubule-like constructure matrix components. expressed markers including AQP1 (proximal tubule), WT1 PODO (podocyte), CD31 (vascular...

10.3390/ijms25010682 article EN International Journal of Molecular Sciences 2024-01-04

Background In the normal heart, phosphodiesterase type 5 (PDE5) hydrolyzes cGMP coupled to nitric oxide– (specifically from oxide synthase 3) but not natriuretic peptide (NP)–stimulated guanylyl cyclase. PDE5 is upregulated in hypertrophied and failing hearts thought contribute their pathophysiology. Because signaling declines whereas NP-derived rises such diseases, we hypothesized that substrate selectivity retargeted blunt signaling. Methods Results Mice with cardiac myocyte inducible...

10.1161/circulationaha.112.090977 article EN Circulation 2012-07-26

We report a mechanism that underlies stress-induced cognitive inflexibility at the molecular level. In mouse model under subacute cellular stress in which deficits rule shifting tasks were elicited, nuclear glyceraldehyde dehydrogenase (N-GAPDH) cascade was activated specifically microglia prelimbic cortex. The normalized with pharmacological intervention compound (the RR compound) selectively blocked initiation of N-GAPDH without affecting glycolytic activity. normalization also observed...

10.1038/s41380-024-02553-1 article EN cc-by Molecular Psychiatry 2024-04-13

The trophoblast (TR) is the first to differentiate during mammalian embryogenesis and play a pivotal role in development of placenta. We used dual inhibitor system (PD0325901 CHIR99021) with mixed feeders successfully obtain bovine stem-like (bTS) cells, which were similar phenotype mouse stem cells (TSCs). bTS that generated using this continually proliferated, displayed normal diploid karyotype, had no signs altered morphology or differentiation even after 150 passages. These exhibited...

10.1089/scd.2013.0329 article EN Stem Cells and Development 2014-03-07

Stimulation of sGC (soluble guanylate cyclase) or inhibition PDE5 (phosphodiesterase type 5) activates PKG (protein kinase G)-1α to counteract cardiac hypertrophy and failure. PKG1α acts within localized intracellular domains; however, its oxidation at cysteine 42, linking homomonomers, alters this localization, impairing suppression pathological stress. Because reside in separate microdomains, we speculated that might also differentially influence the effects from their pharmacological...

10.1161/circheartfailure.117.004740 article EN Circulation Heart Failure 2018-03-01

Trophoblasts (TR) are specialized cells of the placenta and play an important role in embryo implantation. The vitro culture trophoblasts provided tool to investigate mechanisms In present study, porcine trophoblast were derived from pig fertilized (IVF) parthenogenetically activated (PA) blastocysts via culturing medium supplemented with KnockOut serum replacement (KOSR) basic fibroblast growth factor (bFGF) on STO feeder layers, effect ROCK (Rho-associated coiled-coil protein kinases)...

10.1371/journal.pone.0142442 article EN cc-by PLoS ONE 2015-11-10

The establishment of ungulate embryonic stem cells (ESCs) has been notoriously difficult via a conventional approach. We combined traditional ESC culture method with reprogramming factors to assist the porcine naive-like ESCs (nESCs). Pig fibroblasts were transfected tetracycline-inducible vector carrying 4 classic mouse factors, followed by somatic cell nuclear transfer and culturing blastocyst stage. Then, inner mass was isolated seeded in medium. had characteristic verys similar those...

10.1096/fj.201802809r article EN The FASEB Journal 2019-05-24
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