tbuckley/cabot-search huggingface dataset:
Interleukin-1 and the Inflammasome as Therapeutic Targets in Cardiovascular Disease
Authors: Antonio Abbate, Stefano Toldo, Carlo Marchetti, Jordana Kron, Benjamin W. Van Tassell, Charles A. Dinarello
Journal: Circulation Research (2020)

The intracellular sensing protein termed NLRP3 (for NACHT, LRR, and PYD domains-containing protein 3) forms a macromolecular structure called the NLRP3 inflammasome. The NLRP3 inflammasome plays a major role in inflammation, particularly in the production of IL (interleukin)-1β. IL-1β is the most studied of the IL-1 family of cytokines, including 11 members, among which are IL-1α and IL-18. Here, we summarize preclinical and clinical findings supporting the key pathogenetic role of the NLRP3 inflammasome and IL-1 cytokines in the formation, progression, and complications of atherosclerosis, in ischemic (acute myocardial infarction), and nonischemic injury to the myocardium (myocarditis) and the progression to heart failure. We also review the clinically available IL-1 inhibitors, although not currently approved for cardiovascular indications, and discuss other IL-1 inhibitors, not currently approved, as well as oral NLRP3 inflammasome inhibitors currently in clinical development. Canakinumab, IL-1β antibody, prevented the recurrence of ischemic events in patients with prior acute myocardial infarction in a large phase III clinical trial, including 10 061 patients world-wide. Phase II clinical trials show promising data with anakinra, recombinant IL-1 receptor antagonist, in patients with ST-segment–elevation acute myocardial infarction or heart failure with reduced ejection fraction. Anakinra also improved outcomes in patients with pericarditis, and it is now considered standard of care as second-line treatment for patients with recurrent/refractory pericarditis. Rilonacept, a soluble IL-1 receptor chimeric fusion protein neutralizing IL-1α and IL-1β, has also shown promising results in a phase II study in recurrent/refractory pericarditis. In conclusion, there is overwhelming evidence linking the NLRP3 inflammasome and the IL-1 cytokines with the pathogenesis of cardiovascular diseases. The future will likely include targeted inhibitors to block the IL-1 isoforms, and possibly oral NLRP3 inflammasome inhibitors, across a wide spectrum of cardiovascular diseases.
The landscape of RNA polymerase II–associated chromatin interactions in prostate cancer
Authors: Susmita G. Ramanand, Yong Chen, Jiapei Yuan, Kelly Daescu, Maryou B.K. Lambros, Kathleen E. Houlahan, Suzanne Carreira, Wei Yuan, GuemHee Baek, Adam Sharp, Alec Paschalis, Mohammed Kanchwala, Yunpeng Gao, Adam Aslam, Nida Safdar, Xiaowei Zhan, Ganesh V. Raj, Chao Xing, Paul C. Boutros, Johann de Bono, Michael Q. Zhang, Ram S. Mani
Journal: Journal of Clinical Investigation (2020)

Transcriptional dysregulation is a hallmark of prostate cancer (PCa). We mapped the RNA polymerase II-associated (RNA Pol II-associated) chromatin interactions in normal prostate cells and PCa cells. We discovered thousands of enhancer-promoter, enhancer-enhancer, as well as promoter-promoter chromatin interactions. These transcriptional hubs operate within the framework set by structural proteins - CTCF and cohesins - and are regulated by the cooperative action of master transcription factors, such as the androgen receptor (AR) and FOXA1. By combining analyses from metastatic castration-resistant PCa (mCRPC) specimens, we show that AR locus amplification contributes to the transcriptional upregulation of the AR gene by increasing the total number of chromatin interaction modules comprising the AR gene and its distal enhancer. We deconvoluted the transcription control modules of several PCa genes, notably the biomarker KLK3, lineage-restricted genes (KRT8, KRT18, HOXB13, FOXA1, ZBTB16), the drug target EZH2, and the oncogene MYC. By integrating clinical PCa data, we defined a germline-somatic interplay between the PCa risk allele rs684232 and the somatically acquired TMPRSS2-ERG gene fusion in the transcriptional regulation of multiple target genes - VPS53, FAM57A, and GEMIN4. Our studies implicate changes in genome organization as a critical determinant of aberrant transcriptional regulation in PCa.
Obstructive Sleep Apnea, a Risk Factor for Cardiovascular and Microvascular Disease in Patients With Type 2 Diabetes: Findings From a Population-Based Cohort Study
Authors: Nicola J. Adderley, Anuradhaa Subramanian, Konstantinos Toulis, Krishna Gokhale, Thomas Taverner, Wasim Hanif, Shamil Haroon, G. Neil Thomas, Christopher Sainsbury, Abd A. Tahrani, Krishnarajah Nirantharakumar
Journal: Diabetes Care (2020)

OBJECTIVE To determine the risk of cardiovascular disease (CVD), microvascular complications, and mortality in patients with type 2 diabetes who subsequently develop obstructive sleep apnea (OSA) compared with patients with type 2 diabetes without a diagnosis of OSA. RESEARCH DESIGN AND METHODS This age-, sex-, BMI-, and diabetes duration–matched cohort study used data from a U.K. primary care database from 1 January 2005 to 17 January 2018. Participants aged ≥16 years with type 2 diabetes were included. Exposed participants were those who developed OSA after their diabetes diagnosis; unexposed participants were those without diagnosed OSA. Outcomes were composite CVD (ischemic heart disease [IHD], stroke/transient ischemic attack [TIA], heart failure [HF]), peripheral vascular disease (PVD), atrial fibrillation (AF), peripheral neuropathy (PN), diabetes-related foot disease (DFD), referable retinopathy, chronic kidney disease (CKD), and all-cause mortality. The same outcomes were explored in patients with preexisting OSA before a diagnosis of type 2 diabetes versus diabetes without diagnosed OSA. RESULTS A total of 3,667 exposed participants and 10,450 matched control participants were included. Adjusted hazard ratios for the outcomes were as follows: composite CVD 1.54 (95% CI 1.32, 1.79), IHD 1.55 (1.26, 1.90), HF 1.67 (1.35, 2.06), stroke/TIA 1.57 (1.27, 1.94), PVD 1.10 (0.91, 1.32), AF 1.53 (1.28, 1.83), PN 1.32 (1.14, 1.51), DFD 1.42 (1.16, 1.74), referable retinopathy 0.99 (0.82, 1.21), CKD (stage 3–5) 1.18 (1.02, 1.36), albuminuria 1.11 (1.01, 1.22), and all-cause mortality 1.24 (1.10, 1.40). In the prevalent OSA cohort, the results were similar, but some associations were not observed. CONCLUSIONS Patients with type 2 diabetes who develop OSA are at increased risk of CVD, AF, PN, DFD, CKD, and all-cause mortality compared with patients without diagnosed OSA. Patients with type 2 diabetes who develop OSA are a high-risk population, and strategies to detect OSA and prevent cardiovascular and microvascular complications should be implemented.
Results of a Phase 3 Study of Elderly Patients with Newly Diagnosed AML Treated with Sapacitabine and Decitabine Administered in Alternating Cycles
Authors: Hagop M. Kantarjian, Kebede H. Begna, Jessica K. Altman, Stuart L. Goldberg, Mikkael A. Sekeres, Stephen A Strickland, Stephen E. Rubenstein, Martha L. Arellano, David F. Claxton, Maria R. Baer, Marc Gautier, Ellin Berman, Karen Seiter, Scott R Solomon, Gary J. Schiller, Selina Luger, Aleksandra Butrym, Gianluca Gaidano, Xavier Thomas, Pau Montesinos, David A. Rizzieri, Donald P. Quick, Edward Agura, Parameswaran Venugopal, Janakiraman Subramanian, Lori J. Maness, Daniel-Eric Robert, Yosr Hicheri, Tapan Kadia, Farhad Ravandi, Marc E. Buyse, Judy Chiao
Journal: Blood (2017)
Associations of HBV Genotype B vs C Infection With Relapse After Cessation of Entecavir or Tenofovir Therapy
Authors: Shao-Ming Chiu, Yuan-Hung Kuo, Jing-Houng Wang, Chao-Hung Hung, Tsung-Hui Hu, Sheng-Nan Lu, Chien-Hung Chen
Journal: Clinical Gastroenterology and Hepatology (2020)
Intracellular and Intercellular Aspects of Macrophage Immunometabolism in Atherosclerosis
Authors: Ira Tabas, Karin E. Bornfeldt
Journal: Circulation Research (2020)

Macrophage immunometabolism, the changes in intracellular metabolic pathways that alter the function of these highly plastic cells, has been the subject of intense interest in the past few years, in part because macrophage immunometabolism plays important roles in atherosclerosis and other inflammatory diseases. In this review article, part of the Compendium on Atherosclerosis , we introduce the concepts of (1) intracellular immunometabolism—the canonical pathways of intrinsic cell activation leading to changes in intracellular metabolism, which in turn alter cellular function; and (2) intercellular immunometabolism—conditions in which intermediates of cellular metabolism are transferred from one cell to another, thereby altering the function of the recipient cell. The recent discovery that the metabolite cargo of dead and dying cells ingested through efferocytosis by macrophages can alter metabolic pathways and downstream function of the efferocyte is markedly changing the way we think about macrophage immunometabolism. Metabolic transitions of macrophages contribute to their functions in all stages of atherosclerosis, from lesion initiation to formation of advanced lesions characterized by necrotic cores, to lesion regression following aggressive lipid lowering. This review article discusses recent advances in our understanding of these different aspects of macrophage immunometabolism in atherosclerosis. With the increasing understanding of the roles of macrophage immunometabolism in atherosclerosis, new exciting concepts and potential targets for intervention are emerging.
Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia
Authors: Guangchang Pei, Zhiguo Zhang, Jing Peng, Liu Liu, Chunxiu Zhang, Chong Yu, Zufu Ma, Yi Huang, Wei Liu, Ying Yao, Rui Zeng, Gang Xu
Journal: Journal of the American Society of Nephrology (2020)

Some patients with COVID-19 pneumonia also present with kidney injury, and autopsy findings of patients who died from the illness sometimes show renal damage. However, little is known about the clinical characteristics of kidney-related complications, including hematuria, proteinuria, and AKI.
Abstract 17157: Clinical Impact of Digoxin Discontinuation at Hospital Discharge in Patients With Heart Failure With Reduced Ejection Fraction
Authors: Fahad Lodhi, Awais Malik, Syed Z Qamer, Cherinne Arundel, Helen Sheriff, Phillip Lam, Poonam Bhyan, Nankumar Singh, Prakash Deedwania, Gregg Fonarow, Ali Ahmed
Journal: Circulation (2018)

Introduction: Digoxin use is associated with a lower risk of hospital admission and readmission in patients with heart failure with reduced ejection fraction (HFrEF). Moreover, PROVED and RADIANCE trials have shown that digoxin discontinuation is associated with lower ejection fraction (EF), higher heart rate, and worse heart failure (HF) symptoms in chronic HFrEF patients. Despite these results, digoxin use has declined over recent years. In this study, we examined the clinical impact of digoxin discontinuation at hospital discharge in elderly patients with HFrEF. Hypothesis: Digoxin discontinuation at hospital discharge will increase mortality and heart failure readmission in HFrEF patients. Methods: Of 10,625 patients hospitalized with HFrEF (EF≤40%) in Medicare-linked OPTIMIZE-HF registry, 3,225 were receiving digoxin prior to admission but it was discontinued in 655 of these patients at the time of discharge. Propensity scores for digoxin discontinuation, estimated for each of the 3,225 patients, were used to match 616 pairs of patients (digoxin continued vs. discontinued) balanced on 60 baseline characteristics including age (mean 76 years), EF (mean 26%), gender (31% females) and race (15% African America) among others. Results: Among 1,232 matched patients, digoxin discontinuation was associated with a higher risk of all-cause mortality at 30-days (12% vs. 8%; HR 1.45; 95% CI 1.01-2.07; p=0.044) and 6-months (HR 1.32; p=0.009) but not at 1-year (HR 1.18; p=0.07). Digoxin discontinuation was also associated with increased combined heart failure readmission/all-cause mortality at 4-years of follow up (HR 1.16; 95% CI 1.03-1.30; p=0.017). Conclusions: In patients with HFrEF receiving digoxin prior to admission, digoxin discontinuation at discharge from hospital is associated with increased short-term all-cause mortality and long-term heart failure readmission/all-cause mortality.
Exploratory analysis of age and sex dependent DNA methylation patterns on the X-chromosome in whole blood samples
Authors: Shuxia Li, Jesper B. Lund, Kaare Christensen, Jan Baumbach, Jonas Mengel-From, Torben Kruse, Weilong Li, Afsaneh Mohammadnejad, Alison Pattie, Riccardo E. Marioni, Ian J. Deary, Qihua Tan
Journal: Genome Medicine (2020)

Large numbers of autosomal sites are found differentially methylated in the aging genome. Due to analytical difficulties in dealing with sex differences in X-chromosome content and X-inactivation (XCI) in females, this has not been explored for the X chromosome.Using data from middle age to elderly individuals (age 55+ years) from two Danish cohorts of monozygotic twins and the Scottish Lothian Birth Cohort 1921, we conducted an X-chromosome-wide analysis of age-associated DNA methylation patterns with consideration of stably inferred XCI status.Through analysing and comparing sex-specific X-linked DNA methylation changes over age late in life, we identified 123, 293 and 55 CpG sites significant (FDR < 0.05) only in males, only in females and in both sexes of Danish twins. All findings were significantly replicated in the two Danish twin cohorts. CpG sites escaping XCI are predominantly de-methylated with increasing age across cohorts. In contrast, CpGs highly methylated in both sexes are methylated even further with increasing age. Among the replicated sites in Danish samples, 16 (13%), 24 (8.2%) and 3 (5.5%) CpGs were further validated in LBC1921 (FDR < 0.05).The X-chromosome of whole blood leukocytes displays age- and sex-dependent DNA methylation patterns in relation to XCI across cohorts.
Impact of DNA Damage Response and Repair (DDR) Gene Mutations on Efficacy of PD-(L)1 Immune Checkpoint Inhibition in Non–Small Cell Lung Cancer
Authors: Biagio Ricciuti, Gonzalo Recondo, Liam F. Spurr, Yvonne Y. Li, Giuseppe Lamberti, Deepti Venkatraman, Renato Umeton, Andrew D. Cherniack, Mizuki Nishino, Lynette M. Sholl, Geoffrey I. Shapiro, Mark M. Awad, Michael L. Cheng
Journal: Clinical Cancer Research (2020)

DNA damage response and repair (DDR) gene alterations are associated with increased tumor-infiltrating lymphocytes, higher genomic instability, and higher tumor mutational burden (TMB) in cancer. Whether DDR alterations are associated with clinical outcomes to programmed death ligand 1 [PD-(L)1] blockade in non-small cell lung cancer (NSCLC) is unknown.Tumors from patients treated with PD-(L)1 inhibitors were analyzed using targeted next-generation sequencing (NGS). Cancers were categorized on the basis of the presence or absence of deleterious mutations across a panel of 53 DDR genes. Clinical outcomes to PD-(L)1 inhibitors were evaluated according to DDR mutation status.Of 266 patients with successful NGS who received PD-(L)1 inhibitors, 132 (49.6%) were identified as having deleterious DDR mutations (DDR-positive). DDR-positive and DDR-negative groups were similar in terms of baseline clinicopathologic characteristics. The median TMB was significantly higher in the DDR-positive group compared with the DDR-negative group (12.1 vs. 7.6 mutations/megabase; P < 0.001). Compared with DDR-negative patients (N = 134), DDR-positive patients had a significantly higher objective response rate (30.3% vs. 17.2%; P = 0.01), longer median progression-free survival [PFS; 5.4 vs. 2.2 months; HR, 0.58 (95% confidence interval (CI), 0.45-0.76); P < 0.001], and longer median overall survival [OS; 18.8 vs. 9.9 months; HR, 0.57 (95% CI, 0.42-0.77); P < 0.001] with PD-(L)1 therapy. After adjusting for PD-L1, TMB, performance status, tobacco use, and line of therapy, DDR-positive status was associated with a significantly longer PFS [HR, 0.68 (95% CI, 0.51-0.92); P = 0.01] and OS [HR, 0.60 (95% CI, 0.43-0.85); P = 0.004] in multivariate analysis.Deleterious DDR mutations are frequent in NSCLC and are associated with improved clinical outcomes in patients with NSCLC treated with PD-(L)1 blockade.
Abstract 11414: Comparison of 1 Year Pre- and Post-Transcatheter Aortic Valve Replacement Hospitalization Rates: A Population-based Cohort Study
Authors: Andrew Czarnecki, Feng Qiu, Kayley Henning, Jiming Fang, Michelle Jennett, Peter Austin, Dennis T Ko, Sam Radhakrishnan, Harindra C Wijeysundera
Journal: Circulation (2019)

Introduction: Rehospitalization rates post transcatheter aortic valve replacement (TAVR) are high; however, it is not known how these compare to pre-TAVR hospitalization rates. Our objective was to...
Abstract 16244: Helicobacter Pylori Infection Impairs Endothelial Function Through Exosome-Mediated Mechanism
Authors: Xiujuan Xia, Linfang Zhang, Jingshu Chi, Hong Hao, Thomas E Spencer, Canxia Xu, Zhenguo Liu
Journal: Circulation (2019)

Introduction: Atherosclerosis is a major contributor to the development of cardiovascular diseases (CVD). Epidemiological studies have suggested an association between Helicobacter pylori (H. pylor...
Variation in COVID-19 Hospitalizations and Deaths Across New York City Boroughs
Authors: Rishi K. Wadhera, Priya Wadhera, Prakriti Gaba, Jose F. Figueroa, Karen E. Joynt Maddox, Robert W. Yeh, Changyu Shen
Journal: JAMA (2020)

This study describes demographic characteristics and hospital bed capacities of the 5 New York City boroughs, and evaluates whether differences in testing for coronavirus disease 2019 (COVID-19), hospitalizations, and deaths have emerged as a signal of racial, ethnic, and financial disparities.
Repeat laparoscopic hepatectomy for recurrent tumors is safe and feasible. An invited commentary on: “Perioperative outcomes comparing laparoscopic with open repeat liver resection for post-hepatectomy recurrent liver cancer: A systematic review and meta-analysis” (Int. J. Surg. 2020; Epub ahead of print)
Authors: Roberta Angelico, Carlo Gazia
Journal: International Journal of Surgery (2020)
Abstract 14733: Major Adverse Cardiac Events and the Timing and Dose of Corticosteroids in Immune Checkpoint Inhibitor-Associated Myocarditis
Authors: Lili Zhang, Daniel A Zlotoff, Magid Awadalla, Anju Nohria, Syed S Mahmood, Malek Hassan, Franck Thuny, Leyre Zubiri, Sean Murphy, Raza M Alvi, Adam Rokicki, Connor Mulligan, Maeve Jones-O’Connor, Lucie Heinzerling, Ana Barac, Brian Forrestal, Eric H Yang, Carol L Chen, Dipti Gupta, Michael C Kirchberger, Sachin Shah, Otavio R Coelho-Filho, Muhammad Rizvi, Gagan Sahni, Anant Mandawat, Carlo G Tocchetti, Valentina Mercurio, Michael Mahmoudi, Donald P Lawrence, Sarju Ganatra, Stephane Ederhy, John D Groarke, Alexander Lyon, Paaladinesh Thavendiranathan, Ryan J Sullivan, Justine Cohen, Kerry Reynolds, Michael G Fradley, Tomas G Neilan
Journal: Circulation (2019)

Introduction: Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). While corticosteroids are the cornerstones of the treatment, there are no data to guide the dose...
Measurement of Short-Chain Fatty Acids in Respiratory Samples: Keep Your Assay above the Water Line
Authors: Min Yue, Jae Hyun Kim, Charles R. Evans, Maureen Kachman, John R. Erb-Downward, Jennifer D’Souza, Betsy Foxman, Sara D. Adar, Jeffrey L. Curtis, Kathleen A. Stringer
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Avoiding Peg-Filgrastim Prophylaxis During the Paclitaxel Portion of the Dose-Dense Doxorubicin-Cyclophosphamide and Paclitaxel Regimen: A Prospective Study
Authors: Ines Vaz-Luis, Romualdo Barroso-Sousa, Antonio Di Meglio, Jiani Hu, Rebecca Rees, Natalie Sinclair, Lindsey Milisits, Jose Pablo Leone, Michael Constantine, Meredith Faggen, Frederick Briccetti, Caroline Block, Kelly O'Neil, Ann Partridge, Harold Burstein, Adrienne G. Waks, Lorenzo Trippa, Sara M. Tolaney, Michael Hassett, Eric P. Winer, Nancy U. Lin
Journal: Journal of Clinical Oncology (2020)

The use of growth factors adds considerable expense and some toxicity to adjuvant breast cancer chemotherapy. We tested the feasibility and safety of omitting routine peg-filgrastim use during the paclitaxel portion of the dose-dense doxorubicin-cyclophosphamide-paclitaxel regimen.This was a prospective, single-arm study in which patients 18 to 65 years of age who completed 4 cycles of dose-dense doxorubicin-cyclophosphamide for stage I-III breast cancer received paclitaxel 175 mg/m2 every 2 weeks. Peg-filgrastim was administered after paclitaxel only if patients had had febrile neutropenia in a prior cycle or at investigator discretion if patients had infections or treatment delays of > 1 week. Once a patient received peg-filgrastim, it was administered in all future cycles. The primary end point was the rate of paclitaxel completion within 7 weeks from cycle 1 day 1 to cycle 4 day 1. If ≥ 100 out of 125 patients completed 4 cycles of paclitaxel without dose delay, the regimen would be considered feasible.The enrollment goal of 125 patients was met. Median age was 46 years (range, 21-65 years), and 112 patients (90% [95% CI, 83% to 94%]) completed dose-dense paclitaxel within 7 weeks. Omission of peg-filgrastim was not causally related to noncompletion of paclitaxel in any patients. The most common reasons for dose reduction or delays were nonhematologic. One patient experienced febrile neutropenia but was able to complete paclitaxel on time. Eight patients (6.4%) received peg-filgrastim during the trial. Overall, peg-filgrastim was administered in only 4.3% of paclitaxel cycles.Omission of routine peg-filgrastim during dose-dense paclitaxel according to a prespecified algorithm seems to be safe and feasible and was associated with a 95.7% reduction in the use of peg-filgrastim relative to the current standard of care.
<i>Ex vivo</i> Ikkβ ablation rescues the immunopotency of mesenchymal stromal cells from diabetics with advanced atherosclerosis
Authors: Ozge Kizilay Mancini, David N Huynh, Liliane Menard, Dominique Shum-Tim, Huy Ong, Sylvie Marleau, Ines Colmegna, Marc J Servant
Journal: Cardiovascular Research (2020)

Abstract Aims Diabetes is a conventional risk factor for atherosclerotic cardiovascular disease and myocardial infarction (MI) is the most common cause of death among these patients. Mesenchymal stromal cells (MSCs) in patients with type 2 diabetes mellitus (T2DM) and atherosclerosis have impaired ability to suppress activated T-cells (i.e. reduced immunopotency). This is mediated by an inflammatory shift in MSC-secreted soluble factors (i.e. pro-inflammatory secretome) and can contribute to the reduced therapeutic effects of autologous T2DM and atherosclerosis-MSC post-MI. The signalling pathways driving the altered secretome of atherosclerosis- and T2DM-MSC are unknown. Specifically, the effect of IκB kinase β (IKKβ) modulation, a key regulator of inflammatory responses, on the immunopotency of MSCs from T2DM patients with advanced atherosclerosis has not been studied. Methods and results MSCs were isolated from adipose tissue obtained from patients with (i) atherosclerosis and T2DM (atherosclerosis+T2DM MSCs, n = 17) and (ii) atherosclerosis without T2DM (atherosclerosis MSCs, n = 17). MSCs from atherosclerosis+T2DM individuals displayed an inflammatory senescent phenotype and constitutively expressed active forms of effectors of the canonical IKKβ nuclear factor-κB transcription factors inflammatory pathway. Importantly, this constitutive pro-inflammatory IKKβ signature resulted in an altered secretome and impaired in vitro immunopotency and in vivo healing capacity in an acute MI model. Notably, treatment with a selective IKKβ inhibitor or IKKβ knockdown (KD) (clustered regularly interspaced short palindromic repeats/Cas9-mediated IKKβ KD) in atherosclerosis+T2DM MSCs reduced the production of pro-inflammatory secretome, increased survival, and rescued their immunopotency both in vitro and in vivo. Conclusions Constitutively active IKKβ reduces the immunopotency of atherosclerosis+T2DM MSC by changing their secretome composition. Modulation of IKKβ in atherosclerosis+T2DM MSCs enhances their myocardial repair ability.