tbuckley/cabot-search huggingface dataset:
Inhibition of mitophagy drives macrophage activation and antibacterial defense during sepsis
Authors: Danish Patoli, Franck Mignotte, Valérie Deckert, Alois Dusuel, Adélie Dumont, Aurélie Rieu, Antoine Jalil, Kevin Van Dongen, Thibaut Bourgeois, Thomas Gautier, Charlène Magnani, Naig Le Guern, Stéphane Mandard, Jean Bastin, Fatima Djouadi, Christine Schaeffer, Nina Guillaumot, Michel Narce, Maxime Nguyen, Julien Guy, Auguste Dargent, Jean-Pierre Quenot, Mickaël Rialland, David Masson, Johan Auwerx, Laurent Lagrost, Charles Thomas
Journal: Journal of Clinical Investigation (2020)

Mitochondria have emerged as key actors of innate and adaptive immunity. Mitophagy has a pivotal role in cell homeostasis, but its contribution to macrophage functions and host defense remains to be delineated. Here, we showed that lipopolysaccharide (LPS) in combination with IFN-γ inhibited PINK1-dependent mitophagy in macrophages through a STAT1-dependent activation of the inflammatory caspases 1 and 11. In addition, we demonstrated that the inhibition of mitophagy triggered classical macrophage activation in a mitochondrial ROS-dependent manner. In a murine model of polymicrobial infection (cecal ligature and puncture), adoptive transfer of Pink1-deficient bone marrow or pharmacological inhibition of mitophagy promoted macrophage activation, which favored bactericidal clearance and led to a better survival rate. Reciprocally, mitochondrial uncouplers that promote mitophagy reversed LPS/IFN-γ-mediated activation of macrophages and led to immunoparalysis with impaired bacterial clearance and lowered survival. In critically ill patients, we showed that mitophagy was inhibited in blood monocytes of patients with sepsis as compared with nonseptic patients. Overall, this work demonstrates that the inhibition of mitophagy is a physiological mechanism that contributes to the activation of myeloid cells and improves the outcome of sepsis.
Feasibility of Inpatient Continuous Glucose Monitoring During the COVID-19 Pandemic: Early Experience
Authors: Sirimon Reutrakul, Matthew Genco, Harley Salinas, Robert M. Sargis, Carlie Paul, Yuval Eisenberg, Jiali Fang, Rachel N. Caskey, Sarah Henkle, Sam Fatoorehchi, Amanda Osta, Pavan Srivastava, Alexia Johnson, Sarah E. Messmer, Michelle Barnes, Sarida Pratuangtham, Brian T. Layden
Journal: Diabetes Care (2020)

Continuous glucose monitoring (CGM) systems have been explored in a few studies for non-intensive care unit (ICU) patients (1-3).During the coronavirus disease 2019 (COVID-19) pandemic, shortage of personal protective equipment (PPE) became a concern.On 1 April 2020, the U.S. Food and Drug Administration announced it would not object to the use of CGM systems to assist with COVID-19 patient monitoring (4).This study was conducted to explore the feasibility of using CGM in noncritically ill patients hospitalized with COVID-19.Non-ICU adult COVID-19-positive patients receiving subcutaneous insulin injection and point of care (POC) glucose testing (Accu-Chek Inform II) were eligible to participate.Exclusion criteria included unstable glucose levels (POC glucose ,70 or .350mg/dL) at entry, hypotension, significant edema, being on dialysis, being postsurgical or with planned surgery/computed tomography/ MRI, and taking hydroxyurea, ascorbic acid, or acetaminophen .1 g every 6 h.
Association of Triglyceride Deposit Cardiomyovasculopathy With Drug-Eluting Stent Restenosis Among Patients With Diabetes
Authors: Yusuke Nakano, Mayu Suzuki, Ken-ichi Hirano, Hirohiko Ando, Hiroaki Takashima, Hiroshi Takahashi, Tetsuya Amano
Journal: JAMA Network Open (2020)

This cohort study uses data from a single-center cardiac catheter database to investigate the association of cardiac stent restenosis in patients with diabetes mellitus and comorbid triglyceride deposit cardiomyovasculopathy.
Allocation of COVID-19 Relief Funding to Disproportionately Black Counties
Authors: Pragya Kakani, Amitabh Chandra, Sendhil Mullainathan, Ziad Obermeyer
Journal: JAMA (2020)

Samrachana Adhikari, PhD; Nicholas P. Pantaleo, MPH; Justin M. Feldman, ScD; Olugbenga Ogedegbe, MD; Lorna Thorpe, PhD; Andrea B. Troxel, ScD
When Sex Chromosomes Recombine Only in the Heterogametic Sex: Heterochiasmy and Heterogamety in<i>Hyla</i>Tree Frogs
Authors: Christophe Dufresnes, Alan Brelsford, Felix Baier, Nicolas Perrin
Journal: Molecular Biology and Evolution (2020)

Abstract Sex chromosomes are classically predicted to stop recombining in the heterogametic sex, thereby enforcing linkage between sex-determining (SD) and sex-antagonistic (SA) genes. With the same rationale, a pre-existing sex asymmetry in recombination is expected to affect the evolution of heterogamety, for example, a low rate of male recombination might favor transitions to XY systems, by generating immediate linkage between SD and SA genes. Furthermore, the accumulation of deleterious mutations on nonrecombining Y chromosomes should favor XY-to-XY transitions (which discard the decayed Y), but disfavor XY-to-ZW transitions (which fix the decayed Y as an autosome). Like many anuran amphibians, Hyla tree frogs have been shown to display drastic heterochiasmy (males only recombine at chromosome tips) and are typically XY, which seems to fit the above expectations. Instead, here we demonstrate that two species, H. sarda and H. savignyi, share a common ZW system since at least 11 Ma. Surprisingly, the typical pattern of restricted male recombination has been maintained since then, despite female heterogamety. Hence, sex chromosomes recombine freely in ZW females, not in ZZ males. This suggests that heterochiasmy does not constrain heterogamety (and vice versa), and that the role of SA genes in the evolution of sex chromosomes might have been overemphasized.
Genome-Wide Association Study (GWAS) Identifies SNPs in GPR56 and IGF1R Predictive of Leukemic Cell In Vitro cytarabine Sensitivity in Pediatric AML
Authors: Salma Bargal, Roya Rafiee, Kristine R Crews, Xueyuan Cao, Jeffrey E Rubnitz, Stanley Pounds, Jatinder Lamba
Journal: Blood (2017)
The Bbv Regimen: A Phase II Study with Bendamustine Plus Brentuximab Vedotin in Hodgkin Lymphoma and CD30+ Peripheral T-Cell Lymphoma in First Salvage Setting
Authors: Vittorio Stefoni, Beatrice Casadei, Barbara Botto, Paolo Corradini, Antonello Pinto, Alessandro Re, Stefania Badiali, Lisa Argnani, Pier Luigi Zinzani
Journal: Blood (2017)
ROS-responsive capsules engineered from EGCG-Zinc networks improve therapeutic angiogenesis in mouse limb ischemia
Authors: Zuoguan Chen, Jianwei Duan, Yongpeng Diao, Youlu Chen, Xiaoyu Liang, Huiyang Li, Yuqing Miao, Qing Gao, Liang Gui, Xiaoli Wang, Jing Yang, Yongjun Li
Journal: Bioactive Materials (2020)

The successful treatment of limb ischemia requires that promote angiogenesis along with microenvironment improvement. Zinc ions have been reported to stimulate angiogenesis, but application was limited to the toxicity concerns. We hypothesized that zinc based metal-EGCG capsule (EGCG/Zn Ps) can achieve sustained release Zn2+ resulting in reduced toxicity and improve angiogenesis as well as the improvement of microenvironment by ROS scavenging of EGCG. The surface morphology, zeta potential, infrared absorbance peaks and zinc ion release profile of the EGCG/Zn Ps were measured. In vitro, EGCG/Zn showed significantly antioxidant, anti-inflammatory and induced cell migration effect. In addition, EGCG/Zn Ps enabled the sustained release of zinc ions, which reduced cytotoxicity and enhanced the secretion of vascular endothelial growth factor (VEGF) in vitro and in vivo. In mouse models of limb ischemia, EGCG/Zn Ps promoted angiogenesis and cell proliferation in ischemic tissues. Moreover, EGCG/Zn Ps group exhibited the most significant recovery of limb ischemic score, limb temperature and blood flow than other groups. In conclusion, EGCG/Zn Ps is a safe and promising approach to combine the merit of Zn2+ and EGCG, thus enabling the direct application to limb ischemia.
Abstract 19225: Quality and Quantity of Daily Life Activity and Elevation of Central Venous Pressure During Physical Activity are Important Determinants of Hepatic Congestion in Patients With Fontan Circulation
Authors: Akiko Yana, Seiko Kuwata, Clara Kurishima, Hirofumi Saiki, Yoichi Iwamoto, Hirotaka Ishido, Satoshi Masutani, Hideaki Senzaki
Journal: Circulation (2017)

Background: Central venous pressure (CVP) readily increases with physical activity (PA) in patients with Fontan circulation. In fact, we recently reported increased daily PA to be associated with h...
Inotuzumab ozogamicin for relapsed/refractory acute lymphoblastic leukemia: outcomes by disease burden
Authors: Daniel J. DeAngelo, Anjali S. Advani, David I. Marks, Matthias Stelljes, Michaela Liedtke, Wendy Stock, Nicola Gökbuget, Elias Jabbour, Akil Merchant, Tao Wang, Erik Vandendries, Alexander Neuhof, Hagop Kantarjian, Susan O’Brien
Journal: Blood Cancer Journal (2020)

Abstract Adults with relapsed/refractory acute lymphoblastic leukemia (R/R ALL) have a poor prognosis, especially if disease burden is high. This post hoc analysis of the phase 3 INO-VATE trial examined the efficacy and safety of inotuzumab ozogamicin (InO) vs. standard of care chemotherapy (SC) among R/R ALL patients with low, moderate, or high disease burden, respectively, defined as bone marrow blasts (BMB) &lt; 50% ( n = 53 vs. 48), 50–90% ( n = 79 vs. 83), and &gt;90% ( n = 30 vs. 30). Patients in the InO vs. SC arm with low, moderate, and high BMB%, respectively, had improved rates of complete remission/complete remission with incomplete hematologic recovery (74% vs. 46% [ p = 0.0022], 75 vs. 27% [ p &lt; 0.0001], and 70 vs. 17% [ p &lt; 0.0001]), and improved overall survival (hazard ratio: 0.64 [ p = 0.0260], 0.81 [ p = 0.1109], and 0.60 [ p = 0.0335]). Irrespective of BMB%, cytopenias were the most common treatment-emergent adverse events, and post-transplant veno-occlusive disease was more common with InO vs. SC. Patients with extramedullary disease or lymphoblastic lymphoma showed similar efficacy and safety outcomes. This favorable benefit-to-risk ratio of InO treatment irrespective of disease burden supports its use in challenging and high disease burden subpopulations. INO-VATE is registered at www.clinicaltrials.gov : #NCT01564784.
Whole genome sequencing identifies genetic variants associated with co-trimoxazole hypersensitivity in Asians
Authors: Chuang-Wei Wang, Wichittra Tassaneeyakul, Chun-Bing Chen, Wei-Ti Chen, Yu-Chuan Teng, Cheng-Yang Huang, Chonlaphat Sukasem, Chun-Wei Lu, Yun-Shien Lee, Siew-Eng Choon, Nontaya Nakkam, Rosaline Chung-Yee Hui, Yen-Hua Huang, Ya-Ching Chang, Yang Yu-Wei Lin, Chee-Jen Chang, Tsu-Man Chiu, Wasun Chantratita, Parinya Konyoung, Chaw-Ning Lee, Jettanong Klaewsongkram, Ticha Rerkpattanapipat, Warayuwadee Amornpinyo, Niwat Saksit, Pawinee Rerknimitr, Yu Huei Huang, Shang-Hung Lin, Chao-Kai Hsu, Cheng-Chi Chan, Yu-Jr Lin, Shuen-Iu Hung, Wen-Hung Chung
Journal: Journal of Allergy and Clinical Immunology (2020)
CRISPR-Cas9-Mediated ELANE Mutation Correction in Hematopoietic Stem and Progenitor Cells to Treat Severe Congenital Neutropenia
Authors: Ngoc Tung Tran, Robin Graf, Annika Wulf-Goldenberg, Maria Stecklum, Gabriele Strauß, Ralf Kühn, Christine Kocks, Klaus Rajewsky, Van Trung Chu
Journal: Molecular Therapy (2020)

Severe congenital neutropenia (SCN) is a monogenic disorder. SCN patients are prone to recurrent life-threatening infections. The main causes of SCN are autosomal dominant mutations in the ELANE gene that lead to a block in neutrophil differentiation. In this study, we use CRISPR-Cas9 ribonucleoproteins and adeno-associated virus (AAV)6 as a donor template delivery system to repair the ELANEL172P mutation in SCN patient-derived hematopoietic stem and progenitor cells (HSPCs). We used a single guide RNA (sgRNA) specifically targeting the mutant allele, and an sgRNA targeting exon 4 of ELANE. Using the latter sgRNA, ∼34% of the known ELANE mutations can in principle be repaired. We achieved gene correction efficiencies of up to 40% (with sgELANE-ex4) and 56% (with sgELANE-L172P) in the SCN patient-derived HSPCs. Gene repair restored neutrophil differentiation in vitro and in vivo upon HSPC transplantation into humanized mice. Mature edited neutrophils expressed normal elastase levels and behaved normally in functional assays. Thus, we provide a proof of principle for using CRISPR-Cas9 to correct ELANE mutations in patient-derived HSPCs, which may translate into gene therapy for SCN. Severe congenital neutropenia (SCN) is a monogenic disorder. SCN patients are prone to recurrent life-threatening infections. The main causes of SCN are autosomal dominant mutations in the ELANE gene that lead to a block in neutrophil differentiation. In this study, we use CRISPR-Cas9 ribonucleoproteins and adeno-associated virus (AAV)6 as a donor template delivery system to repair the ELANEL172P mutation in SCN patient-derived hematopoietic stem and progenitor cells (HSPCs). We used a single guide RNA (sgRNA) specifically targeting the mutant allele, and an sgRNA targeting exon 4 of ELANE. Using the latter sgRNA, ∼34% of the known ELANE mutations can in principle be repaired. We achieved gene correction efficiencies of up to 40% (with sgELANE-ex4) and 56% (with sgELANE-L172P) in the SCN patient-derived HSPCs. Gene repair restored neutrophil differentiation in vitro and in vivo upon HSPC transplantation into humanized mice. Mature edited neutrophils expressed normal elastase levels and behaved normally in functional assays. Thus, we provide a proof of principle for using CRISPR-Cas9 to correct ELANE mutations in patient-derived HSPCs, which may translate into gene therapy for SCN.
Abstract 10957: 1-year High-intensity Exercise Training Reverses Abnormal Left Ventricular Myocardial Stiffness in Patients With Stage B HFpEF
Authors: Michinari Hieda, Satyam Sarma, Christopher Hearon, Katrin Dias, James MacNamara, Dean Palmer, Jose Martinez, Mitchel Samels, Braden Everding, Sheryl A Livingston, Margot Morris, Benjamin D Levine
Journal: Circulation (2019)

Introduction: Individuals with left ventricular hypertrophy (LVH) and elevated cardiac biomarkers in middle-age are at increased risk for the development of heart failure with preserved ejection fr...
A Novel System for Newborn Screening of Thalassemia and Hemoglobinopathies Using Capillary Electrophoresis Is Superior Than Isoelectric Focusing
Authors: Thidarat Suksangpleng, Suchada Riolueang, Jiraporn Korchuenjit, Wasamon Korchuenjit, Julaporn Pooliam, Vip Viprakasit
Journal: Blood (2017)
Abstract 11181: Discovery of Neurovascular Reactivity During a Standard 5-minute Arm-cuff Reactive Hyperemia - Data From 7105 Patient Registry
Authors: Ruoyu Zhuang, Ahmed Gul, Albert Yen, Hirofumi Tanaka, Ralph Metcalfe, Stanley Kleis, Morteza Naghavi
Journal: Circulation (2019)

Background: Endothelial function testing using a 5-minute arm-cuff occlusion have always focused on hemodynamic measures from the occluded arm. No publication is found in PubMed (as of May 2019) on...
DPHL: A DIA Pan-Human Protein Mass Spectrometry Library for Robust Biomarker Discovery
Authors: Tiansheng Zhu, Yi Zhu, Yue Xuan, Huanhuan Gao, Xue Cai, Sander R. Piersma, Thang V. Pham, Tim Schelfhorst, Richard R.G.D. Haas, Irene V. Bijnsdorp, Rui Sun, Liang Yue, Guan Ruan, Qiushi Zhang, Mo Hu, Yue Zhou, Winan J. Van Houdt, Tessa Y.S. Le Large, Jacqueline Cloos, Anna Wojtuszkiewicz, Danijela Koppers-Lalic, Franziska Böttger, Chantal Scheepbouwer, Ruud H. Brakenhoff, Geert J.L.H. van Leenders, Jan N.M. Ijzermans, John W.M. Martens, Renske D.M. Steenbergen, Nicole C. Grieken, Sathiyamoorthy Selvarajan, Sangeeta Mantoo, Sze S. Lee, Serene J.Y. Yeow, Syed M.F. Alkaff, Nan Xiang, Yaoting Sun, Xiao Yi, Shaozheng Dai, Wei Liu, Tian Lu, Zhicheng Wu, Xiao Liang, Man Wang, Yingkuan Shao, Xi Zheng, Kailun Xu, Qin Yang, Yifan Meng, Cong Lu, Jiang Zhu, Jin'e Zheng, Bo Wang, Sai Lou, Yibei Dai, Chao Xu, Chenhuan Yu, Huazhong Ying, Tony K. Lim, Jianmin Wu, Xiaofei Gao, Zhongzhi Luan, Xiaodong Teng, Peng Wu, Shi'ang Huang, Zhihua Tao, Narayanan G. Iyer, Shuigeng Zhou, Wenguang Shao, Henry Lam, Ding Ma, Jiafu Ji, Oi L. Kon, Shu Zheng, Ruedi Aebersold, Connie R. Jimenez, Tiannan Guo
Journal: Genomics Proteomics & Bioinformatics (2020)

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to generate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.
Integrative Genomic Analysis Reveals Four Protein Biomarkers for Platelet Traits
Authors: Dong Heon Lee, Chen Yao, Arunoday Bhan, Thorsten Schlaeger, Joshua Keefe, Benjamin A.T. Rodriguez, Shih-Jen Hwang, Ming-Huei Chen, Daniel Levy, Andrew D. Johnson
Journal: Circulation Research (2020)

Rationale: Mean platelet volume (MPV) and platelet count (PLT) are platelet measures that have been linked to cardiovascular disease (CVD) and mortality risk. Identifying protein biomarkers for these measures may yield insights into CVD mechanisms. Objective: We aimed to identify causal protein biomarkers for MPV and PLT among 71 CVD-related plasma proteins measured in FHS (Framingham Heart Study) participants. Methods and Results: We conducted integrative analyses of genetic variants associated with PLT/MPV with protein quantitative trait locus variants associated with plasma proteins followed by Mendelian randomization to infer causal relations of proteins for PLT/MPV. We also tested protein-PLT/MPV association in FHS participants. Using induced pluripotent stem cell-derived megakaryocyte clones that produce functional platelets, we conducted RNA-sequencing and analyzed expression differences between low- and high-platelet producing clones. We then performed small interfering RNA gene knockdown experiments targeting genes encoding proteins with putatively causal platelet effects in megakaryocyte clones to examine effects on platelet production. In protein-trait association analyses, ten proteins were associated with MPV and 31 with PLT. Mendelian randomization identified 4 putatively causal proteins for MPV and 4 for PLT. GP-5 (Glycoprotein V), GRN (granulin), and MCAM (melanoma cell adhesion molecule) were associated with PLT, while MPO (myeloperoxidase) showed significant association with MPV in both analyses. RNA-sequencing analysis results were directionally concordant with observed and Mendelian randomization-inferred associations for GP-5, GRN, and MCAM. In siRNA gene knockdown experiments, silencing GP-5, GRN, and MPO decreased PLTs. Genome-wide association study results suggest several of these may be linked to CVD risk. Conclusions: We identified 4 proteins that are causally linked to PLTs. These proteins may also have roles in the pathogenesis of CVD via a platelet/blood coagulation-based mechanism.
John Richard Robinson: pioneered the concept of therapeutic psychiatric communities
Authors: Roger Jones
Journal: BMJ (2020)

John Robinson always wanted to be a psychiatrist. Over his almost 30 years at the Littlemore Hospital in Oxford, through the creation and promotion of therapeutic psychiatric communities, he made a national and international contribution to the care of patients with acute psychiatric illness and of older patients with mental health problems and dementia. In his memoir O, To Be a Doctor (Frontier Publishing, 2012) he describes, with characteristic modesty, his rich medical and personal life, and identifies numerous experiences that sensitised him to the need for a more patient centred, enlightened, and collaborative approach to psychiatry.

As a medical student on a paediatric attachment, he experienced Dermot McCarthy’s innovative practice of having a parent to stay with the patient in hospital—“what a wonderful insight into the creative power of emotional attachment.” He describes a ward …
Quantitative Fluxomics of Circulating Metabolites
Authors: Sheng Hui, Alexis J. Cowan, Xianfeng Zeng, Lifeng Yang, Tara TeSlaa, Xiaoxuan Li, Caroline Bartman, Zhaoyue Zhang, Cholsoon Jang, Lin Wang, Wenyun Lu, Jennifer Rojas, Joseph Baur, Joshua D. Rabinowitz
Journal: Cell Metabolism (2020)
Human mAbs Broadly Protect against Arthritogenic Alphaviruses by Recognizing Conserved Elements of the Mxra8 Receptor-Binding Site
Authors: Laura A. Powell, Andrew Miller, Julie M. Fox, Nurgun Kose, Thomas Klose, Arthur S. Kim, Robin Bombardi, Rashika N. Tennekoon, A. Dharshan de Silva, Robert H. Carnahan, Michael S. Diamond, Michael G. Rossmann, Richard J. Kuhn, James E. Crowe
Journal: Cell Host & Microbe (2020)
Nanotherapeutics for regeneration of degenerated tissue infected by bacteria through the multiple delivery of bioactive ions and growth factor with antibacterial/angiogenic and osteogenic/odontogenic capacity
Authors: Ahmed El-Fiqi, Nandin Mandakhbayar, Seung Bin Jo, Jonathan C. Knowles, Jung-Hwan Lee, Hae-Won Kim
Journal: Bioactive Materials (2020)

Therapeutic options are quite limited in clinics for the successful repair of infected/degenerated tissues. Although the prevalent treatment is the complete removal of the whole infected tissue, this leads to a loss of tissue function and serious complications. Herein the dental pulp infection, as one of the most common dental problems, was selected as a clinically relevant case to regenerate using a multifunctional nanotherapeutic approach. For this, a mesoporous bioactive glass nano-delivery system incorporating silicate, calcium, and copper as well as loading epidermal growth factor (EGF) was designed to provide antibacterial/pro-angiogenic and osteo/odontogenic multiple therapeutic effects. Amine-functionalized Cu-doped bioactive glass nanospheres (Cu-BGn) were prepared to be 50–60 nm in size, mesoporous, positive-charged and bone-bioactive. The Cu-BGn could release bioactive ions (copper, calcium and silicate ions) with therapeutically-effective doses. The Cu-BGn treatment to human umbilical vein endothelial cells (HUVEC) led to significant enhancement of the migration, tubule formation and expression of angiogenic gene (e.g. vascular endothelial growth factor, VEGF). Furthermore, the EGF-loaded Cu-BGn ([email protected]) showed pro-angiogenic effects with antibacterial activity against E. faecalis, a pathogen commonly involved in the pulp infection. Of note, under the co-culture condition of HUVEC with E. faecalis, the secretion of VEGF was up-regulated. In addition, the osteo/odontogenic stimulation of the [email protected] was evidenced with human dental pulp stem cells. The local administration of the [email protected] in a rat molar tooth defect infected with E. faecalis revealed significant in vivo regenerative capacity, highlighting the nanotherapeutic uses of the multifunctional nanoparticles for regenerating infected/damaged hard tissues.