tbuckley/cabot-search huggingface dataset:
Abstract 4909: Nox2-Containing NADPH Oxidase Deficiency Protects Against Age-Dependent Inhibition of Neovascularization
Authors: Julie Turgeon, Paola Haddad, Sylvie Dussault, Jessika Groleau, Fritz Maingrette, Gemma Perez, Alain Rivard
Journal: Circulation (2009)

Background: We have previously shown that aging is associated with an impaired angiogenic response following ischemia. Because aging leads to an increased generation of reactive oxygen species (ROS), here we investigated the role of Nox2-containing NADPH oxidase ROS generation for the modulation of neovascularization by aging. Methods: Hindlimb ischemia was surgically induced by femoral artery removal in young (5–7 weeks) and older (9 months) Nox2 −/− and control (Nox2 +/+ ) mice. Results: We found that blood flow recovery is significantly reduced in older compared to younger mice at day 21 after surgery (Doppler flow ratios: 0.51± 0.05 vs. 0.72± 0.05; p&lt;0.05). At the microvascular level, capillary density was also significantly reduced in ischemic muscles of older animals (53.4± 6.3 capillaries/field vs. 82.5± 4.9 capillaries/field; p&lt;0.001). This was associated with a significant increase of oxidative stress levels (nitrotyrosine immunostaining) in ischemic tissues of older animals. Importantly, we found that Nox2 deficiency reduces oxidative stress levels in ischemic tissues and restores blood flow recuperation in older animals. Endothelial progenitor cells (EPCs) have been shown to have an important role for postnatal neovascularization. Here we found that the functional activities of EPCs (adhesion to HUVECs, migration) are significantly impaired in old compared to young mice. However, Nox2 deficiency rescues EPCs functional activities in older animals. We also demonstrate an age-dependent pathological increase of oxidative stress levels (DCF-DA, DHE) in EPCs that is not present in Nox2-deficient animals. Conclusion: Nox2-containing NADPH oxidase deficiency protects against age-dependent impairment of neovascularization. Potential mechanisms include reduced ROS generation in ischemic tissues and preserved angiogenic activities of EPCs.
Injectable thermo-sensitive hydrogel enhances anti-tumor potency of engineered Lactococcus lactis by activating dendritic cells and effective memory T cells
Authors: Aoxing Chen, Junmeng Zhu, Rui Liu, Yi Mei, Lin Li, Yue Fan, Yaohua Ke, Baorui Liu, Qin Liu
Journal: Bioactive Materials (2024)

Engineered bacteria have shown great potential in cancer immunotherapy by dynamically releasing therapeutic payloads and inducing sustained antitumor immune response with the crosstalk of immune cells. In previous studies, FOLactis was designed, which could secret an encoded fusion protein of Fms-related tyrosine kinase 3 ligand and co-stimulator OX40 ligand, leading to remarkable tumor suppression and exerting an abscopal effect by intratumoral injection. However, it is difficult for intratumoral administration of FOLactis in solid tumors with firm texture or high internal pressure. For patients without lesions such as abdominal metastatic tumors and orthotopic gastric tumors, intratumoral injection is not feasible and peritumoral maybe a better choice. Herein, an engineered bacteria delivery system is constructed based on in situ temperature-sensitive poloxamer 407 hydrogels. Peritumoral injection of FOLactis/P407 results in a 5-fold increase in the proportion of activated DC cells and a more than 2-fold increase in the proportion of effective memory T cells (T
Abstract 17126: Tackling Cardiovascular Disease Risk in Primary Care: Does Sex Matter?
Authors: Jafna L Cox, Claudine C Szpilfogel, Pantelis Andreou, Terrance M Vallis, Brendan S Carr, Blair J O'Neill
Journal: Circulation (2011)

Purpose: To ascertain whether men and women respond differently to an intervention intended to decrease cardiovascular disease (CVD) risk in primary care (PC) through individualized systematic risk factor screening, risk-weighted behavioral counseling and pharmacological treatment. Methods: We studied two geographically diverse PC practices in Nova Scotia, Canada, with differing reimbursement models vs a comparison group. Patients completed a health risk assessment (HRA) and readiness to change assessment that triggered an intervention individualized around both parameters with 1-year follow-up and a final HRA. The primary endpoint was the proportion of subjects with moderate and high baseline 10-year Framingham Risk Scores reducing risk by 10% and 25%, respectively. Sex-differences in response to the intervention were explored. Results: 1509 intervention patients enrolled; 72% completed the study. Results are presented for 561 subjects with moderate or high baseline Framingham risk but no diabetes or established CVD. Mean age was 55.4 years; 57.8% were female. 43% vs 31% controls achieved the primary endpoint (p=0.06, ARR = 12%, RRR = 38%, NNT=9). Females (ARR=15%, RRR=46%, NNT= 7) did better than males (ARR=5.2%, RRR=17.2%, NNT=20). When comparing sexes, there was significantly greater reduction in systolic blood pressure (p&lt; 0.001) and a higher increase in HDL cholesterol (p=0.04) for females. Significantly more (p &lt; 0.0001) females changed their metabolic syndrome status (prevalence 93.5% vs 58.6% pre and post intervention, respectively) vs. males (59.5% vs. 46.8% pre and post intervention, respectively). The specific metabolic syndrome risk factors that drove the difference included waist circumference (p &lt;0.0001), HDL cholesterol (p=0.03) and blood pressure (p=0.04). These results were obtained largely through lifestyle modification; drug use did not change significantly. Conclusion: In an intervention to improve CVD risk in primary care, women did better than men. Differences were seen especially around improved metabolic risk, predominantly as a result of lifestyle change. These findings suggest that prevention programs may need to modify their approaches according to patient sex.
A scaffold vaccine to promote tumor antigen cross-presentation via sustained toll-like receptor-2 (TLR2) activation
Authors: Daping Xie, Congwei Han, Chonghao Chen, Zhencheng Liao, Senio Campos de Souza, Yiming Niu, João F. Mano, Lei Dong, Chunming Wang
Journal: Bioactive Materials (2024)

Cancer vaccination holds great promise for cancer treatment, but its effectiveness is hindered by suboptimal activation of CD8
Abstract 17112: Impact of Hyperparathyroidism on Left Ventricular Structure: A Meta Analysis of 367 Patients
Authors: Rory Hachamovitch, Sinziana Seicean, Thomas Cook, Thomas Marwick
Journal: Circulation (2011)

Background. Primary hyperparathyroidism (PHPT) is associated with an increased risk of cardiovascular mortality. To date, studies comparing left ventricular (LV) structure in patients (pts) with untreated PHPT to controls have reported mixed results. To this end, we performed a meta-analysis of studies comparing LV structure in untreated PHPT pts versus controls using echocardiographic techniques. Methods. The published literature was scanned using searches of electronic databases (PubMed, MEDLINE) and references of relevant articles. The primary echocardiographic metrics included LV mass index (LVMI), LV posterior wall thickness (PWT), and interventricular septal thickness (IVST). PHPT pts were compared to controls with respect to pooled estimates of difference in means and 95% confidence intervals (95%CI) using a weighted random effects model. Results. We identified 12 studies that including 367 PHPT pts and 404 controls (76% female, 74 years, parathyroid hormone 4.0 times normal). In these studies, LVMI was greater in PHPT pts versus controls (9 studies; p=0.045; difference in means 9.4 gram/m2, 95%CI 0.2-18.6). This difference was related to increases in both IVST (p=0.002; difference in means 0.47mm, 95%CI 0.17-0.77) and PWT (p=0.047; difference in means 0.47mm, 95%CI 0.01-0.94). No differences in systolic or diastolic LV volumes were noted, or in fractional shortening (all p=NS). Diastolic function, as measured by E/A and interventricular relaxation time was also unchanged (all p=NS). Conclusions. Compared to controls, pts with untreated PHPT have greater LV mass index and LV wall thickness without alteration in LV volumes or function. These findings may contribute to the increased cardiovascular risk found in these pts.
Hydrogel-exosome system in tissue engineering: A promising therapeutic strategy
Authors: Ming-Hui Fan, Jin-Kui Pi, Chen-Yu Zou, Yan-Lin Jiang, Qian-Jin Li, Xiu-Zhen Zhang, Fei Xing, Rong Nie, Chen Han, Hui-Qi Xie
Journal: Bioactive Materials (2024)

Characterized by their pivotal roles in cell-to-cell communication, cell proliferation, and immune regulation during tissue repair, exosomes have emerged as a promising avenue for "cell-free therapy" in clinical applications. Hydrogels, possessing commendable biocompatibility, degradability, adjustability, and physical properties akin to biological tissues, have also found extensive utility in tissue engineering and regenerative repair. The synergistic combination of exosomes and hydrogels holds the potential not only to enhance the efficiency of exosomes but also to collaboratively advance the tissue repair process. This review has summarized the advancements made over the past decade in the research of hydrogel-exosome systems for regenerating various tissues including skin, bone, cartilage, nerves and tendons, with a focus on the methods for encapsulating and releasing exosomes within the hydrogels. It has also critically examined the gaps and limitations in current research, whilst proposed future directions and potential applications of this innovative approach.
Abstract 18777: Glucagon-like Peptide-1 Inhibits Thrombin-induced Human Platelet Aggregation
Authors: Alison Cameron-Vendrig, Adili Reheman, Talat Afroze, Hossein Noyan-Ashraf, Heyu Ni, Mansoor Husain
Journal: Circulation (2012)

Background: Studies of glycemic control in diabetics receiving glucagon-like peptide-1 (GLP-1)-targeted drugs have suggested reduced incidences of cardiovascular events over 6-12 months. Mechanisms underlying this surprisingly rapid effect are not known. Methods &amp; Results: To investigate potential anti-thrombotic effects of GLP-1 and related analogs, we tested GLP-1(7-36)NH2, the most abundant endogenous GLP-1, and the commercially available GLP-1 analog exenatide in thrombin-induced platelet aggregation assays using freshly isolated gel-filtered human platelets (3x108/ml) in normoglycemic conditions (5.5mM glucose). Incubation with GLP-1 (10-10 to 10-6 M) or exenatide (5x10-10 to 10-8 M) for 15 min at 37°C delayed and reduced platelet aggregation as compared to PBS-treated controls. GLP-1 (10^-9M) resulted in a 60% decrease in aggregation 1 min after thrombin stimulation. To investigate whether this effect may be mediated by a GLP-1 receptor (R), whole cell lysates (40 µg) from gel-filtered human platelets and the human megakaryocyte (MGK) cell line MEG-01 were probed with a polyclonal anti- GLP-1R Ab (1:1250; Santa Cruz). Although Western blot showed bands (∼56 kD) consistent with the known GLP-1R in both platelets and MEG-01 cells, GAPDH-normalized expression levels of GLP-1R were ∼13 and ∼45 fold lower in these cells than in human pancreas. Given the limited specificity of Abs raised against GPCRs, RT-PCR was performed on RNA from MEG-01 cells with primers designed to yield full-length human GLP-1R cDNA. PCR products were cloned and sequenced, revealing inserts identical to GLP-1R. As this receptor is known to be adenylate cyclase-coupled, cAMP assays were also performed (EIA kit, Cayman Chemicals). MEG-01 cells incubated for 15 min with 10-7 M GLP-1 showed a ∼60% increase in intracellular cAMP, an inhibitor of platelet activation, as compared to untreated controls; while the cAMP response to prostacyclin PGI2 was much greater (positive control; 16 fold). Conclusion: Human platelets and MGK express low levels of GLP-1R. While GLP-1 induced only small increases in cAMP in MGK, both GLP-1 and exenatide inhibited thrombin-induced platelet aggregation. These data suggest that GLP-1-targeted drugs may possess anti-platelet effects.
4D bioprinting of programmed dynamic tissues
Authors: Jiahui Lai, Yuwei Liu, Gang Lu, Patrick Yung, Xiaoying Wang, Rocky S. Tuan, Zhong Alan Li
Journal: Bioactive Materials (2024)

Setting time as the fourth dimension, 4D printing allows us to construct dynamic structures that can change their shape, property, or functionality over time under stimuli, leading to a wave of innovations in various fields. Recently, 4D printing of smart biomaterials, biological components, and living cells into dynamic living 3D constructs with 4D effects has led to an exciting field of 4D bioprinting. 4D bioprinting has gained increasing attention and is being applied to create programmed and dynamic cell-laden constructs such as bone, cartilage, and vasculature. This review presents an overview on 4D bioprinting for engineering dynamic tissues and organs, followed by a discussion on the approaches, bioprinting technologies, smart biomaterials and smart design, bioink requirements, and applications. While much progress has been achieved, 4D bioprinting as a complex process is facing challenges that need to be addressed by transdisciplinary strategies to unleash the full potential of this advanced biofabrication technology. Finally, we present future perspectives on the rapidly evolving field of 4D bioprinting, in view of its potential, increasingly important roles in the development of advanced dynamic tissues for basic research, pharmaceutics, and regenerative medicine.
Abstract 19056: Left Ventricle Longitudinal Strain was Reduced in Subclinical Patienst with Repaired Tof
Authors: Akihiro Nakamura, Yoshihiro Seo, Tomoko Ishizu, Yoshiaki Kato, Miho Takahashi, Hitoshi Horigome, Ryo Sumazaki, Kazutaka Aonuma
Journal: Circulation (2012)

Background: Right ventricular (RV) dilation and dysfunction caused by residual pulmonary regurgitation afterh repaired tetralogy of Fallot (ToF) are associated with their prognosis. In contrast, left ventricular (LV) function has been focused as a novel determinant of prognosis in patients with repaired ToF. Although RV-LV interaction may be a cause of LV dysfunction, the reason of LV dysfunction in patients with repaired ToF was poorly understood. We aimed to assess LV regional myocardial function in consideration of interaction with RV properties. Methods: We studied subclinical 27 patients with repaired ToF (11 male, 17.1 ± 4.9yrs) and 10 control subjects (7male, 13.9 ± 5.5yrs). RV and LV ejection fractions (EF) and end diastolic volume index (EDVi, ml/m2) were measured with 3-dimensional echocardiographic sysytem (Tomtec imaging systems). Pulmonary regurgitation(PR) fraction was caliculated by volumetric method [RV stroke volume - LV stroke volume / RV stroke volume]. Tricuspid annular plane systolic excursion (TAPSE) was measured in assessing RV systolic function.Left atrium area(LA), transmitral mitral flow ratio(MVE/A), and velocity ratio of early mitral flow to mitral ring (MV E/E’) were measured for evaluation of LV diastolic function. Global LV and RV longitudinal strain (LS) were assessed by speckle tracking echocardiography. Ramp protocol cardiopulmonary exercise testing was performed to measure peakVO2 (ml/kg/min). Results: PR fraction (31±18%) was correlated with RVEDVi(r=0.532, p=0.001), however, not correlated with TAPSE, RVEF, and RV-LS. LV-LS was lower in patients with repaired ToF compared to control subjects (-29.1±5.7 vs -23.8±4.8 %, p=0.014). LV-LS was negatively correlated with PR fraction (r= -0.435, p=0.008), and RVEDV(r= -0.491,p=0.002). However, no correlation between RV-LS and LV-LS was observed. LV-LS was negatively associated with LA (r= -0.392, p=0.018), but not associated with MV E/A, MV E/E’ and peak VO2. Conclusions: Even in subclinical patienst with repaired ToF, LV-LS was reduced as comoared to normal subjects. The longitudinal dysfunction may be rather affected by dilated RV, and clininical significance with LV diastolic function and exercise capacity were not clear in this setting.
Abstract 19261: The Association Between Testosterone Replacement Therapy and Adverse Cardiovascular Outcomes in Veterans Undergoing Coronary Angiography
Authors: Rebecca Vigen, Al Barqawi, Thomas M Maddox, Gary Grunwald, Colin O'Donnell, James Enright, P M Ho
Journal: Circulation (2012)

Background: Adverse cardiac events were not demonstrated in randomized controlled trials of testosterone replacement therapy (TRT) in men until 2009 when the Testosterone in Older Men with Mobility Limitations trial was halted due to increased cardiac events in the treatment group. Therefore, the safety of TRT in older men with medical comorbidities is under debate. Methods: We used the VA CART-CL registry to identify all veterans undergoing coronary angiography between 2005 and 2011 who had total testosterone levels ≤ 250 ng/dL measured post-procedure. We derived a propensity-matched (2:1) cohort of patients dispensed TRT to patients not dispensed TRT. Multivariable Cox regression assessed the association between TRT and myocardial infarction (MI) or death treating TRT as a time varying covariate. We also evaluated this association within strata of CAD: no CAD, nonobstructive CAD (&gt;20% stenosis in any vessel), and obstructive CAD (≥ 70% in any vessel or ≥ 50% in the left main). Results: Of the 3,375 veterans who had a total testosterone level ≤ 250, 461 (12%) were initiated on TRT after a mean of 546 days (median 463 days) after coronary angiography. No significant differences were observed in the baseline characteristics of the TRT and non-TRT propensity matched groups including mean age (61), hypertension (89%), diabetes (55%), and mean testosterone level (166). In multivariable analyses, there was a significant interaction between TRT and CAD strata (p=0.04). Among veterans with no CAD or nonobstructive CAD, there was no association between TRT and MI/death (p=0.46 and p=0.3, respectively). Among those with obstructive CAD, TRT was associated with significantly increased risk of MI/death (HR 2.51; 95% CI 1.6 - 3.94). Conclusion: In this cohort of veterans undergoing coronary angiography with low testosterone levels, TRT can be associated with increased risk of MI/death as compared to no TRT. This risk appears to be present in patients with obstructive CAD but not among patients with less severe CAD. These findings may have potential implications for targeting testosterone use among selected patient populations.
Abstract 18970: Angiotensin-(1-7) Enhances the Regenerative Capacity of Cardiac Progenitor Cells (CPCs, Islet-1 <sup>+</sup> ) in Ischemia-induced Cardiac Injury Model
Authors: Yanfei Qi, Erin Bruce, Shenoy Vinayak, Colleen Jeffrey, Meng Liu, Fan Lin, Wei Yuan, Joseph Abbatematteo,, Michael Katovich, Mohan Raizada
Journal: Circulation (2012)

Stem cell therapy has achieved limited success to provide sufficient exogenous reparative support in ischemic heart diseases (IHD). We evaluated the hypothesis that transduction of CPCs with Ang-(1-7) would improve their regenerative capacity, as this peptide has been shown to improve hematopoietic progenitor cell functions. First, we determined if Ang-(1-7) improves CPC functions in vitro . Angiogenesis and migratory potential of CPCs, lenti-Ang-(1-7) transduced CPCs and CPCs treated with 1µM Ang-(1-7) were evaluated. Ang-(1-7) enhanced the CPC capability to form tubes; protected CPCs from hypoxia (H) induced inhibition of migration (CPC 688.7 ± 52.8, H treated CPC 124.5 ± 187.7, H+lenti-Ang-(1-7) 617.2 ± 45.4, H+1µM Ang-(1-7) 878.8 ± 303.9; RFU); reduced ACE mRNA level in the CPCs and shifted the balance to the vasoprotective axis of the RAS. Next, in vivo studies were carried out by injecting CPCs or lenti-Ang-(1-7) transduced CPCs (4 × 10 6 ), into the jugular vein three days after permanent left anterior descending coronary artery ligation. Echocardiography, hemodynamic, histological parameters, and capillary vessel density were measured to assess cardiac function and the effects of cell transplantation four weeks thereafter. Results from the in vivo studies demonstrated that myocardial infarction (MI) significantly reduced fractional shortening (FS, 33.0% ± 1.5 vs 59.5% ± 1.9 for control), increased ventricular hypertrophy (VH, 3.6 ± 0.1 vs 2.7 ± 0.1for control, (g/kg)), and decreased dP/dt max (7235 ± 271.9 vs 10394 ± 326.3 for control, mmHg/sec). In comparison to MI, CPCs alone restored FS by 22%, reversed VH by 11%, and improved dP/dt max by 23%. Remarkably, Ang-(1-7) expressing CPCs further improved FS by 44%, decreased VH by 15%, and attenuated the reduction in dP/dt max by 42%. Finally, capillary density in the peri-infarct myocardium was increased by 59% with CPCs alone and this capillary density was further increased by 139% with Ang-(1-7) expressing CPCs. In conclusion, these observations, for the first time, demonstrate that Ang-(1-7) enhances the regenerative capacity of CPCs and promotes angiogenesis to improve cardiac hemodynamic following MI. They suggest that Ang-(1-7) transduced CPC could have therapeutic potential in IHD.
Abstract 19078: Cardiac Troponin T Measured by a Highly Sensitive Assay is Associated with Diabetes Incidence
Authors: Seamus Whelton, Mariana Lazo, Eun Jung Park, Josef Coresh, J. H Young, Frederick Brancati, Ron Hoogeveen, Christie Ballantyne, Elizabeth Selvin
Journal: Circulation (2012)

Introduction: An adverse cardiovascular disease (CVD) risk factor profile is typically present well before the clinical diagnosis of diabetes. Diabetes and hyperglycemia are risk factors for myocardial damage and subclinical atherosclerosis, but it is unclear if subclinical cardiac damage is present before the clinical diagnosis of diabetes. Hypothesis: Subclinical myocardial damage_as indicated by elevated cardiac troponin measured by a novel highly sensitive assay (hs-cTnT) will be associated with risk of diabetes. Methods: We conducted a prospective cohort analysis of hs-cTnT and incidence of self-reported diabetes among ARIC study participants with no known history of diabetes or CVD at baseline (1996-98). Adjusted Cox proportional hazard models included hs-cTnT as a categorical variable or as a spline. Results: During a median of 12 years of follow-up of 7,898 participants, there were 1,809 self-reported cases of newly diagnosed diabetes. Compared to those with undetectable hs-cTnT (&lt;0.003ug/L), participants with hs-cTnT 0.009-0.0013 or ≥0.014ug/L had a significantly increased risk for diabetes after adjustment for diabetes risk factors: HRs of 1.18, 95% CI 1.0-1.40 and 1.32, 95% CI 1.04 - 1.69, respectively. After further adjustment for glucose, the relationship was attenuated (p-values for linear trend 0.01 before and 0.19 after adjustment) but was significant when modeled non-linearly (p-value=0.003 for spline with knot at the mean hs-cTnT of 0.005 ug/L) (Figure). Conclusions: Elevated levels of hs-cTnT are associated with an increased risk of developing diabetes even in the absence of a history of CVD and after adjusting for diabetes risk factors but the association is non-linear after adjustment for fasting glucose. This suggests that diabetes and heart disease may develop in parallel with myocyte necrosis preceding as well as following diabetes.