Publications by authors named "Daokun Sun"

11 Publications

  • Page 1 of 1

Impact of Body Mass Index on Outcome of Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy.

Ann Thorac Surg 2021 Mar 24. Epub 2021 Mar 24.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.

Background: Obesity is highly prevalent in patients with obstructive hypertrophic cardiomyopathy (HCM). In this study, we investigated the impact of body mass index (BMI) in patients undergoing septal myectomy (SM) for obstructive HCM.

Methods: We reviewed 2,746 patients who underwent transaortic SM for obstructive HCM from February 1993 through September 2018. Patients were stratified into 3 groups based on BMI (normal weight < 25 kg/m, overweight 25 to < 30 kg/m, and obese ≥ 30 kg/m).

Results: Preoperatively, median left ventricular outflow tract (LVOT) gradient was 58 mmHg, and there was no difference in gradients across BMI strata (P=0.35). Obese patients had lower percentage with moderate or greater mitral valve regurgitation (45.8%) compared to normal (52.9%) and overweight (55.4%) patients (P<0.001). However, patients with higher BMI were more likely to have New York Heart Association class III/IV limitation at presentation (P<0.001). After myectomy, both anteroseptal thickness (P=0.115) and LVOT gradient (P=0.210) did not differ between groups. There were 14 (0.5%) deaths < 30 days postoperatively and the risk was similar across BMI strata (P=0.448). Model-estimated changes in average BMI at 10 years post procedure showed stratum-specific increases ranging from 0.60 to 1.56 kg/m. During a median (IQR) follow-up of 7.2 (3.2-13.3) years, higher BMI was associated with reduced survival after adjusting for baseline covariates (P=0.001).

Conclusions: Septal myectomy is safe and effective in HCM patients with obesity, but risk of late mortality increased with increasing BMI. Attention to risk factor management through weight loss may improve late results after SM.
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http://dx.doi.org/10.1016/j.athoracsur.2021.03.038DOI Listing
March 2021

Nonobstructive Hypertrophic Cardiomyopathy in a Patient with Mitral Prosthesis.

Ann Thorac Surg 2020 Dec 8. Epub 2020 Dec 8.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.

Transapical septal myectomy can be performed for patients with nonobstructive hypertrophic cardiomyopathy (HCM) and diastolic dysfunction to enlarge the left ventricular cavity. The procedure may also include limited shaving of severely hypertrophied papillary muscles. This report illustrates the usefulness of papillary muscle resection to enlarge the left ventricle in a patient with nonobstructive HCM and pre-existing mitral valve prosthesis.
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http://dx.doi.org/10.1016/j.athoracsur.2020.09.059DOI Listing
December 2020

Association of blood pressure with cognitive function at midlife: a Mendelian randomization study.

BMC Med Genomics 2020 08 26;13(1):121. Epub 2020 Aug 26.

Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, 1825 Pressler Street, Houston, TX, 77030, USA.

Background: Whether high blood pressure has a causal effect on cognitive function as early as middle age is unclear. We investigated whether high blood pressure (BP) causally impairs cognitive function at midlife using Mendelian Randomization (MR).

Methods: We applied a two-sample MR approach to investigate the causal relationship between BP and midlife cognitive performance measured by the Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), and Stroop Interference test. We used a total of 109 genetic polymorphisms with established associations with BP as instrumental variables and estimated gene-cognitive function association in 1369 middle-aged adults (Mean age (SD): 50.8 (3.3), 54.0% women) from the CARDIA study.

Results: A 10 mmHg increment in genetically-predicted systolic, diastolic, or pulse pressure was associated with a 4.9 to 7.7-point lower DSST score (P = 0.002, SBP; P = 0.005, DBP and P = 0.008, PP), while a 10 mmHg increment in genetically-predicted SBP was associated with a 0.7 point lower RAVLT and a 2.3 point higher Stroop (P = 0.046 and 0.011, respectively).

Conclusions: This MR analysis shows that high BP, especially SBP, is causally associated with poorer processing speed, verbal memory, and executive function during midlife. These findings emphasize the need for further investigation of the role and mechanisms of BP dysregulation on cognitive health in middle age and perhaps, more broadly, across the lifespan.
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http://dx.doi.org/10.1186/s12920-020-00769-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448985PMC
August 2020

Transapical Septal Myectomy for Hypertrophic Cardiomyopathy With Midventricular Obstruction.

Ann Thorac Surg 2021 03 6;111(3):836-844. Epub 2020 Aug 6.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.

Background: Midventricular obstruction (MVO) is an uncommon variant of hypertrophic cardiomyopathy (HCM). In patients receiving septal myectomy for HCM, failure to recognize the concurrent MVO in the context of basal septum thickening can lead to inadequate excision and residual gradient. In this report, we detail the operative outcomes of MVO with and without coexistent basal septal hypertrophy.

Methods: From February 1997 through September 2018, 196 patients underwent midventricular myectomy. Medical records and follow-up databases were reviewed to obtain patient characteristics and perioperative features.

Results: At baseline, 156 patients (80%) were in New York Heart Association Functional Classification III/IV. Obstruction was isolated to the midventricle in 80 patients, and 63 (79%) were treated by isolated transapical myectomy. The remaining 116 patients had intraventricular obstruction at both subaortic and midcavity levels; in 108 (93%), a combined transaortic and transapical approach was adopted to achieve complete relief of the obstruction. After septal myectomy, the resting peak instantaneous gradient decreased from a median 48 mm Hg (interquartile range [IQR], 23-77 mm Hg) preoperatively to 8 mm Hg (IQR, 0-19 mm Hg) before hospital dismissal. Median follow-up was 2.9 years (IQR, 0.7-5.0 years), and the estimated 1-, 5-, and 10-year survivals were 99%, 98%, and 90%, respectively. There were no late complications attributable to the transapical incision.

Conclusions: Transapical exposure is a safe and effective approach for relief of midventricular obstruction, and hemodynamic results are similar to those achieved by standard myectomy for subaortic obstruction. The technique can be combined with transaortic myectomy for patients with left ventricular outflow obstruction at both levels.
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http://dx.doi.org/10.1016/j.athoracsur.2020.05.182DOI Listing
March 2021

Phylogenetic analysis of two single-copy nuclear genes revealed origin of tetraploid barley Hordeum marinum.

PLoS One 2020 30;15(6):e0235475. Epub 2020 Jun 30.

College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, China.

Sea barley Hordeum marinum is an important germplasm resource. However, the origin of this tetraploid H. marinum subsp. gussoneanum is still unclear, which has caused great perplexity to the exploration and utilization of germplasm resources. We used two single-copy nuclear genes, thioredoxin-like gene (TRX) and waxy1 gene encoding granule-bound starch synthase (WAXY1) to analyze 41 accessions of Hordeum marinum. The phylogenies of different genes told different story of evolution of tetraploids of H. marinum subsp. gussoneanum. The phylogenetic trees showed that two distinct copies of sequences from both genes were detected for some accessions of the tetraploids of H. marinum subsp. gussoneanum, and diploid marinum might also contribute to the origin and evolution of the tetraploid gussoneanum. Our findings suggested that tetraploid more likely originated from the diploids of H. marinum subsp. gussoneanum and another ancestor that might be an extinct unknown diploid species. Homogenization of gene in tetraploids also occurred after polyploidization as both TRX and WAXY1 sequences in some accessions of tetraploid H. marinum subsp. gussoneanum cannot be distinguished, indicating the complicated evolution of this tetraploid.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235475PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326175PMC
September 2020

Two Distinct E2F Transcriptional Modules Drive Cell Cycles and Differentiation.

Cell Rep 2019 06 23;27(12):3547-3560.e5. Epub 2019 May 23.

Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address:

Orchestrating cell-cycle-dependent mRNA oscillations is critical to cell proliferation in multicellular organisms. Even though our understanding of cell-cycle-regulated transcription has improved significantly over the last three decades, the mechanisms remain untested in vivo. Unbiased transcriptomic profiling of G, G-S, and S-G-M sorted cells from FUCCI mouse embryos suggested a central role for E2Fs in the control of cell-cycle-dependent gene expression. The analysis of gene expression and E2F-tagged knockin mice with tissue imaging and deep-learning tools suggested that post-transcriptional mechanisms universally coordinate the nuclear accumulation of E2F activators (E2F3A) and canonical (E2F4) and atypical (E2F8) repressors during the cell cycle in vivo. In summary, we mapped the spatiotemporal expression of sentinel E2F activators and canonical and atypical repressors at the single-cell level in vivo and propose that two distinct E2F modules relay the control of gene expression in cells actively cycling (E2F3A-8-4) and exiting the cycle (E2F3A-4) during mammalian development.
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http://dx.doi.org/10.1016/j.celrep.2019.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6673649PMC
June 2019

A prospective study of serum metabolites and risk of ischemic stroke.

Neurology 2019 04 13;92(16):e1890-e1898. Epub 2019 Mar 13.

From the Brown Foundation Institute of Molecular Medicine, McGovern Medical School (D.S., X.J., M.F.), and School of Public Health (B.Y., E.B., M.F.), The University of Texas Health Science Center at Houston; Institute for Stroke and Dementia Research (S.T., M.D.), Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany; Johns Hopkins University School of Medicine (R.F.G.), Baltimore, MD; The University of Mississippi Medical Center (T.H.M.), Jackson; German Center for Neurodegenerative Diseases (DZNE, Munich) (M.D.); and Munich Cluster for Systems Neurology (SyNergy) (S.T., M.D.), Germany.

Objective: To identify promising blood-based biomarkers and novel etiologic pathways of disease risk, we applied an untargeted serum metabolomics profiling in a community-based prospective study of ischemic stroke (IS).

Methods: In 3,904 men and women from the Atherosclerosis Risk In Communities study, Cox proportional hazard models were used to estimate the association of incident IS with the standardized level of 245 fasting serum metabolites individually, adjusting for age, sex, race, field center, batch, diabetes, hypertension, current smoking status, body mass index, and estimated glomerular filtration rate. Validation of results was carried out in an independent sample of 114 IS cases and 112 healthy controls.

Results: Serum levels of 2 long-chain dicarboxylic acids, tetradecanedioate and hexadecanedioate, were strongly correlated ( = 0.88) and were associated with incident IS after adjusting for covariates (hazard ratio [95% confidence interval (CI)] 1.11 [1.06-1.16] and 1.12 [1.07-1.17], respectively; < 0.0001). Analyses by IS subtypes suggested that these associations were specific to cardioembolic stroke (CES). Associations of tetradecanedioate and hexadecanedioate with IS were independently confirmed (odds ratio [95% CI] 1.76 [1.21; 2.56] and 1.60 [1.11; 2.32], respectively).

Conclusion: Two serum long-chain dicarboxylic acids, metabolic products of ω-oxidation of fatty acids, were associated with IS and CES independently of known risk factors. Pathways related to intracellular hexadecanedioate synthesis or those involved in its clearance from the circulation may mediate IS risk. These results highlight the potential of metabolomics to discover novel circulating biomarkers for stroke and to unravel novel pathways for IS and its subtypes.
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http://dx.doi.org/10.1212/WNL.0000000000007279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6550501PMC
April 2019

E2f8 mediates tumor suppression in postnatal liver development.

J Clin Invest 2016 08 25;126(8):2955-69. Epub 2016 Jul 25.

E2F-mediated transcriptional repression of cell cycle-dependent gene expression is critical for the control of cellular proliferation, survival, and development. E2F signaling also interacts with transcriptional programs that are downstream of genetic predictors for cancer development, including hepatocellular carcinoma (HCC). Here, we evaluated the function of the atypical repressor genes E2f7 and E2f8 in adult liver physiology. Using several loss-of-function alleles in mice, we determined that combined deletion of E2f7 and E2f8 in hepatocytes leads to HCC. Temporal-specific ablation strategies revealed that E2f8's tumor suppressor role is critical during the first 2 weeks of life, which correspond to a highly proliferative stage of postnatal liver development. Disruption of E2F8's DNA binding activity phenocopied the effects of an E2f8 null allele and led to HCC. Finally, a profile of chromatin occupancy and gene expression in young and tumor-bearing mice identified a set of shared targets for E2F7 and E2F8 whose increased expression during early postnatal liver development is associated with HCC progression in mice. Increased expression of E2F8-specific target genes was also observed in human liver biopsies from HCC patients compared to healthy patients. In summary, these studies suggest that E2F8-mediated transcriptional repression is a critical tumor suppressor mechanism during postnatal liver development.
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http://dx.doi.org/10.1172/JCI85506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966321PMC
August 2016

The Rho-GEF Gef3 interacts with the septin complex and activates the GTPase Rho4 during fission yeast cytokinesis.

Mol Biol Cell 2015 Jan 19;26(2):238-55. Epub 2014 Nov 19.

Department of Molecular Genetics Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH 43210

Rho GTPases, activated by Rho guanine nucleotide exchange factors (GEFs), are conserved molecular switches for signal transductions that regulate diverse cellular processes, including cell polarization and cytokinesis. The fission yeast Schizosaccharomyces pombe has six Rho GTPases (Cdc42 and Rho1-Rho5) and seven Rho GEFs (Scd1, Rgf1-Rgf3, and Gef1-Gef3). The GEFs for Rho2-Rho5 have not been unequivocally assigned. In particular, Gef3, the smallest Rho GEF, was barely studied. Here we show that Gef3 colocalizes with septins at the cell equator. Gef3 physically interacts with septins and anillin Mid2 and depends on them to localize. Gef3 coprecipitates with GDP-bound Rho4 in vitro and accelerates nucleotide exchange of Rho4, suggesting that Gef3 is a GEF for Rho4. Consistently, Gef3 and Rho4 are in the same genetic pathways to regulate septum formation and/or cell separation. In gef3∆ cells, the localizations of two potential Rho4 effectors--glucanases Eng1 and Agn1--are abnormal, and active Rho4 level is reduced, indicating that Gef3 is involved in Rho4 activation in vivo. Moreover, overexpression of active Rho4 or Eng1 rescues the septation defects of mutants containing gef3∆. Together our data support that Gef3 interacts with the septin complex and activates Rho4 GTPase as a Rho GEF for septation in fission yeast.
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http://dx.doi.org/10.1091/mbc.E14-07-1196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294672PMC
January 2015

SNP-revealed genetic diversity in wild emmer wheat correlates with ecological factors.

BMC Evol Biol 2013 Aug 13;13:169. Epub 2013 Aug 13.

Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Chinese Academy of Sciences, Wuhan, Hubei 430074, China.

Background: Patterns of genetic diversity between and within natural plant populations and their driving forces are of great interest in evolutionary biology. However, few studies have been performed on the genetic structure and population divergence in wild emmer wheat using a large number of EST-related single nucleotide polymorphism (SNP) markers.

Results: In the present study, twenty-five natural wild emmer wheat populations representing a wide range of ecological conditions in Israel and Turkey were used. Genetic diversity and genetic structure were investigated using over 1,000 SNP markers. A moderate level of genetic diversity was detected due to the biallelic property of SNP markers. Clustering based on Bayesian model showed that grouping pattern is related to the geographical distribution of the wild emmer wheat. However, genetic differentiation between populations was not necessarily dependent on the geographical distances. A total of 33 outlier loci under positive selection were identified using a FST-outlier method. Significant correlations between loci and ecogeographical factors were observed.

Conclusions: Natural selection appears to play a major role in generating adaptive structures in wild emmer wheat. SNP markers are appropriate for detecting selectively-channeled adaptive genetic diversity in natural populations of wild emmer wheat. This adaptive genetic diversity is significantly associated with ecological factors.
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http://dx.doi.org/10.1186/1471-2148-13-169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751623PMC
August 2013

Genetic diversity revealed by single nucleotide polymorphism markers in a worldwide germplasm collection of durum wheat.

Int J Mol Sci 2013 Mar 28;14(4):7061-88. Epub 2013 Mar 28.

Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Chinese Academy of Sciences, Wuhan 430074, Hubei, China.

Evaluation of genetic diversity and genetic structure in crops has important implications for plant breeding programs and the conservation of genetic resources. Newly developed single nucleotide polymorphism (SNP) markers are effective in detecting genetic diversity. In the present study, a worldwide durum wheat collection consisting of 150 accessions was used. Genetic diversity and genetic structure were investigated using 946 polymorphic SNP markers covering the whole genome of tetraploid wheat. Genetic structure was greatly impacted by multiple factors, such as environmental conditions, breeding methods reflected by release periods of varieties, and gene flows via human activities. A loss of genetic diversity was observed from landraces and old cultivars to the modern cultivars released during periods of the Early Green Revolution, but an increase in cultivars released during the Post Green Revolution. Furthermore, a comparative analysis of genetic diversity among the 10 mega ecogeographical regions indicated that South America, North America, and Europe possessed the richest genetic variability, while the Middle East showed moderate levels of genetic diversity.
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http://dx.doi.org/10.3390/ijms14047061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645677PMC
March 2013