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the HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

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Bone research 2024年第2期12卷 289-301页

作者： Heeseog Kang Amy L.Strong Yuxiao Sun Lei Guo Conan Juan Alec C.Bancroft Ji Hae Choi Chase A.Pagani Aysel A.Fernandes Michael Woodard Juhoon Lee sowmya ramesh Aaron W.James David Hudson Kevin N.Dalby Lin Xu robert J.tower Benjamin Levi Center for Organogenesis Regeneration and TraumaDepartment of SurgeryUniversity of Texas SouthwesternDallasTX 75390USA Section of Plastic Surgery Department of SurgeryUniversity of MichiganAnn ArborMI 48109USA Quantitative Biomedical research Center Peter O’Donnell Jr.School of Public HealthUniversity of Texas SouthwesternDallasTX 75390USA Department of Orthopedics and Sports Medicine University of WashingtonSeattleWA 98195USA Division of Chemical Biology and Medicinal Chemistry College of PharmacyUniversity of Texas at AustinAustinTX 78712USA Department of Pathology Johns Hopkins UniversityBaltimoreMD 21218USA

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be ***(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal *** andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote ***,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to ***,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell ***-cell rNA sequencing(scrNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in *** mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreEr^(t2);Hif1a^(fl/fl))significantly mitigated HO in ***-seq analysis of these Hoxa11-CreEr^(t2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of ***,our scrNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α*** a translational aspect,a pan-LOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic *** suggests that the HIF-1α/PLOD2/LOX axis linked tometabolism regulates HO-forming MPC *** results suggest that the HIF-1α/PLOD2/LOX pathway represents a promisingstrategy to mitigate HO formation.

关键词： metabolism skeletal aberrant

Spectrum of cardiac manifestations and its relationship to outcomes in patients admitted with scrub typhus infection

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World Journal of Critical Care Medicine 2018年第1期7卷 16-23页

作者： Gunasekaran Karthik thomas Isaiah Sudarsan John Victor Peter thambu Sudarsanam George M Varghese Paul Kundavaram sowmya Sathyendra ramya Iyyadurai Kishore Pichamuthu Department of Medicine Christian Medical College Medical Intensive Care Unit Christian Medical College Department of Infectious Diseases Christian Medical College

AIM to study the spectrum of cardiac manifestations in scrub typhus infection and assess its relationship to *** Demographic data, electrocardiographic(ECG) changes, left ventricular (LV) systolic and diastolic function, myocardial injury (defined as troponin t > 14 pg/mL), and pericardial effusion were documented. Myocarditis was diagnosed when myocardial injury was associated with global LV systolic dysfunction. the relationship between myocarditis and outcomes was assessed using logistic regression analysis and expressed as odds ratio(Or) with 95%*** the cohort(n = 81; 35 males) aged 49.4 ± 16.1 years(mean, SD) presented 8.1 ± 3.1 d after symptom onset. the APACHE-Ⅱ score was 15.7 ± 7.0. Fortyeight (59%) patients were ventilated, and 46 (56%) required vasoactive agents. Mortality was 9.9%. ECG changes were non-specific; sinus tachycardia was the most common finding. Myocardial injury was evident in 61.7% of patients and LV systolic dysfunction in 30.9%. A diagnosis of myocarditis was made in 12.3%. In addition, seven patients with regional wall motion abnormalities had LV systolic dysfunction and elevated cardiac enzymes. Mild diastolic dysfunction was observed in 18 (22%) patients. Mild to moderate pericardial effusion was seen in 51%. On multivariate logistic regression analysis, patients with myocarditis tended to be older (Or = 1.04, 95%CI: 0.99-1.09), had shorter symptom duration (Or = 0.69, 95%CI: 0.49-0.98), and tended to stay longer in hospital(Or = 1.17, 95%CI: 0.98-1.40). Myocarditis was not associated with increased *** In scrub typhus infection, cardiac manifestations are frequent and associated with increased morbidity but not mortality.

关键词： Scrub typhus Myocarditis Outcome

Characteristics and distinct prognostic determinants of individuals with hepatosplenic t-cell lymphoma over the past two decades

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World Journal of Clinical Oncology 2024年第6期15卷 745-754页

作者： Ayrton Bangolo Pierre Fwelo Shraboni Dey tanni Sethi sowmya Sagireddy Jawaria Chatta Ashish Goel Sneha Nagpaul Eric Pin-Shiuan Chen Chiranjeeve Saravanan Sheeja Gangan Joel thomas Sarah Potiguara Vignesh K Nagesh Daniel Elias Charlene Mansour Prajakta H ratnaparkhi Priyanshu Jain Midhun Mathew taylor Porter Shadiya Sultan Shailaja Abbisetty Linh tran Megha Chawla Abraham Lo Simcha Weissman Christina Cho Department of Internal Medicine Palisades Medical CenterNorth BergenNJ 07047United States Department of Epidemiology Human Geneticsand Environmental SciencesUTHealth School of Public HealthHoustonTX 77030United States Department of Medicine Palisades Medical CenterNorth BergenNJ 07047United States Stem Cell transplantation and Cellular therapy John Theurer Cancer CenterHackensackNJ 07601United States

BACKGrOUND Hepatosplenic t-cell lymphoma(HStCL)is a rare and aggressive peripheral t-cell lymphoma with historically dismal outcomes,representing less than one percent of non-Hodgkin *** its rarity,the true incidence of HStCL is unknown and most data have been extrapolated through case *** the best of our knowledge,the largest and most up to date study addressing the epidemiology and outcomes of patients with HStCL in the United States covered a period from 1996 to 2014,with a sample size of 122 *** to paint the most updated epidemiological picture of *** A total of 186 patients diagnosed with HStCL,between 2000 and 2017,were ultimately enrolled in our study by retrieving data from the Surveillance,Epidemiology,and End results *** analyzed demographics,clinical characteristics,and overall mortality(OM)as well as cancer-specific mortality(CSM)of *** with a P valuethe univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors,with a hazard ratio of greater than 1 representing adverse prog-nostic *** Overall,the outlook for this rare malignancy is very *** this retrospective cohort study of the United States population,non-Hispanic blacks and the elderly had a higher *** data highlights the need for larger prospective studies to investigate factors associated with worse prognosis in one ethnic group,such as treatment delays,which have been shown to increase mortality in this racial/ethnic group for other cancers.

关键词： Extra nodal lymphoma Mortality Survival racial disparity Age

Nature：大规模研究揭示生命所必需的基因

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现代生物医学进展 2016年第31期16卷 I0002-I0003页

作者： Dickinson, Mary E. Flenniken, Ann M. Ji, Xiao teboul, Lydia Wong, Michael D. White, Jacqueline K. Meehan, terrence F. Weninger, Wolfgang J. Westerberg, Henrik Adissu, Hibret Baker, Candice N. Bower, Lynette Brown, James M. Caddle, L. Brianna Chiani, Francesco Clary, Dave Cleak, James Daly, Mark J. Denegre, James M. Doe, Brendan Dolan, Mary E. Edie, Sarah M. Fuchs, Helmut Gailus-Durner, Valerie Galli, Antonella Gambadoro, Alessia Gallegos, Juan Guo, Shiying Horner, Neil r. Hsu, Chih-Wei Johnson, Sara J. Kalaga, sowmya Keith, Lance C. Lanoue, Louise Lawson, thomas N. Lek, Monkol Mark, Manuel Arschall, Susan M. Mason, Jeremy McElwee, Melissa L. Newbigging, Susan Nutter, Lauryl M. J. Peterson, Kevin A. ramirez-Solis, ramiro rowland, Douglas J. ryder, Edward Samocha, Kaitlin E. Seavitt, John r. Selloum, Mohammed Szoke-Kovacs, Zsombor tamura, Masaru trainor, Amanda G. tudose, Ilinca Wakana, Shigeharu Warren, Jonathan Wendling, Olivia West, David B. Wong, Leeyean Yoshiki, Atsushi MacArthur, Daniel G. tocchini-Valentini, Glauco P. Gao, Xiang Flicek, Paul Bradley, Allan Skarnes, William C. Justice, Monica J. Parkinson, Helen E. Moore, Mark Wells, Sara Braun, robert E. Svenson, Karen L. de Angelis, Martin Hrabe Herault, Yann Mohun, tim Mallon, Ann-Marie Henkelman, r. Mark Brown, Steve D. M. Adams, David J. Lloyd, K. C. Kent McKerlie, Colin Beaudet, Arthur L. Bucan, Maja Murray, Stephen A. Dept Mol Physiol & Biophys Houston TX 77030 USA toronto Ctr Phenogen Toronto ON M5T 3H7 Canada Mt Sinai Hosp Toronto ON M5G 1X5 Canada Univ Penn Perelman Sch Med Genom & Computat Biol Program Philadelphia PA 19104 USA Med res Council Harwell Mammalian Genet Unit Harwell OX11 0RD Oxon England Mary Lyon Ctr Harwell OX11 0RD Oxon England Hosp Sick Children Mouse Imaging Ctr Toronto ON M5T 3H7 Canada Wellcome trust Sanger Inst Wellcome Trust Genome Campus Cambridge CB10 1SA England European Bioinformat Inst European Mol Biol Lab Wellcome Trust Genome Campus Cambridge CB10 1SD England Med Univ Vienna Ctr Anat & Cell Biol A-1090 Vienna Austria Hosp Sick Children 555 Univ Ave Toronto ON M5G 1X8 Canada Jackson Lab 600 Main St Bar Harbor ME 04609 USA Univ Calif Davis Mouse Biol Program Davis CA 95618 USA Italian Natl res Council CNr Inst Cell Biol & Neurobiol Monterotondo Mouse Clin I-00015 Monterotondo Italy Massachusetts Gen Hosp Analyt & Translat Genet Unit Boston MA 02114 USA Broad Inst MIt & Harvard Program Med & Populat Genet Cambridge MA 02142 USA German res Ctr Environm Hlth Helmholtz Zentrum Munchen Inst Expt Genet D-85764 Neuherberg Germany German Mouse Clin D-85764 Neuherberg Germany Baylor Coll Med Dept Mol & Human Genet Houston TX 77030 USA Nanjing Univ Nanjing Biomed Res Inst Collaborat Innovat Ctr Genet & Dev SKL Pharmaceut Biotechnol & Model Anim Res Ctr Nanjing 210061 Jiangsu Peoples R China Univ Strasbourg ICS Infrastruct Natl PHENOMIN F-67404 Illkirch Graffenstaden France Univ Strasbourg INSERM CNRS IGBMC F-67404 Illkirch Graffenstaden France rIKEN BioResource Ctr Tsukuba Ibaraki 3050074 Japan Childrens Hosp Oakland Res Inst Oakland CA 94609 USA IMPC San Anselmo CA 94960 USA tech Univ Munich Sch Life Sci Weihenstephan Chair Expt Genet D-81675 Freising Weihenstephan Germany German Ctr Diabet res DZD D-85764 Neuherberg Germany Francis Crick Inst Mill Hill Lab Mill Hill London NW1 1AT England Univ Penn Perlman

在哺乳动物基因组中。大约三分之一的基因是生命所必需的。在一项新的研究中，来自美国贝勒医学院等多个机构的研究人员描述了这些基因的大规模发现。以及它将如何影响对哺乳动物发育和人类疾病的理解。相关研究结果在线发表在Nature期... 详细信息

在哺乳动物基因组中。大约三分之一的基因是生命所必需的。在一项新的研究中，来自美国贝勒医学院等多个机构的研究人员描述了这些基因的大规模发现。以及它将如何影响对哺乳动物发育和人类疾病的理解。相关研究结果在线发表在Nature期刊上，论文标题为“High—throughput discovery of novel developmental phenotypes”。

关键词：动物基因组生命哺乳动物研究人员人类疾病医学院