Optical and molecular longitudinal tracking of primary colorectal murine tumors shows differences in the angiogenic response to maximum-tolerated and metronomic approaches

Abstract Background Despite advances in revascularization strategies, type 2 diabetic (T2D) patients with peripheral artery disease (PAD) continue to have a high risk of limb amputation. Modulation of blood vessel growth holds great promise for the treatment of PAD patients. Epigenetic modifications, namely histone post-translational modifications, have shown to regulate transcriptional programs implicated in the pathogenesis of cardiovascular disease. Aim To investigate the role of chromatin changes in regulating post-ischemic vascularization in experimental diabetes as well as in patients with T2D. Methods Experiments were performed in primary human aortic endothelial cells (HAECs), double-mutant leptin deficient mice (Lepdb/db) carrying a genetic deletion of the methyltransferase SETD7 (Setd7−/−Lepdb/db) as well as in gastrocnemius muscle samples from T2D patients with PAD and age-matched non-diabetic controls. Unbiased gene expression profiling was performed by RNA sequencing (RNA-seq) followed by Ingenuity Pathway Analysis (IPA). Pharmacological blockade of SETD7 was performed by using the selective inhibitor (R)-PFI-2. Scratch and tube formation assays were performed to investigate the impact of SETD7 on angiogenic response. Results RNA-seq in high glucose-treated HAECs revealed a profound upregulation of the methyltransferase SETD7 (fold change 2.8, p<0.001), an enzyme involved in mono-methylation of lysine 4 at histone 3 (H3K4me1). Both SETD7 gene silencing and pharmacological inhibition by (R)PFI-2 rescued hyperglycemia-induced impairment of HAECs migration and tube formation, while SETD7 overexpression blunted the angiogenic response. RNA-seq and Chromatin Immunoprecipitation (ChIP) assays showed that SETD7-dependent H3K4me1 regulates the transcription of the angiogenesis inhibitor semaphorin-3G (SEMA-3G). Increased SEMA-3G transcript was associated with enhanced secretion from HAECs. Co-immunofluorescence experiments showed that SEMA-3G blunts the angiogenic response by competing with VEGF receptors VEGFR/Neuropillin2. Moreover, SEMA-3G overexpression blunted migration and tube formation in SETD7-depleted HAECs. SETD7 and SEMA-3G were significantly upregulated in endothelial cells from Lepdb/db mice, whereas SEMA-3G transcription was blunted in Setd7−/−Lepdb/db animals. Consistently, endothelial sprouting was defective in aortas from Lepdb/db as compared to WT mice, whereas Setd7−/−Lepdb/db mice displayed a preserved angiogenic response. Of clinical relevance, SETD7/SEMA-3G axis was upregulated in gastrocnemius muscle specimens from T2D patients with PAD as compared with non-diabetic controls. Conclusion In HAECs, genetically modified mice and T2D patients we show that SETD7-dependent chromatin changes regulate SEMA-3G transcription and angiogenic response. Pharmacological inhibition of SETD7 may represent a novel epigenetic therapy to boost neovascularization in T2D patients with PAD. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): University of Zurich/Universitätsspital Zürich

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VEGF receptor targeted imaging of angiogenic response to limb ischemia in diabetic vs. non-diabetic Yucatan minipigs

EJNMMI Research ◽

10.1186/s13550-020-00626-0 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Lynne L. Johnson ◽

Jordan Johnson ◽

Ziad Ali ◽

Yared Tekabe ◽

Rebecca Ober ◽

...

Keyword(s):

Limb Ischemia ◽

Vegf Receptor ◽

Targeted Imaging ◽

Angiogenic Response

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Which patient-reported outcomes do rheumatology patients find important to track digitally? A real-world longitudinal study in ArthritisPower

Arthritis Research & Therapy ◽

10.1186/s13075-021-02430-0 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

W. Benjamin Nowell ◽

Kelly Gavigan ◽

Carol L. Kannowski ◽

Zhihong Cai ◽

Theresa Hunter ◽

...

Keyword(s):

Physical Function ◽

Lupus Erythematosus ◽

Patient Reported Outcomes ◽

Treatment Effectiveness ◽

Time Window ◽

Joint Stiffness ◽

Summary Score ◽

Longitudinal Tracking ◽

Patient Reported

Abstract Background Patient-reported outcomes (PROs) are increasingly used to track symptoms and to assess disease activity, quality of life, and treatment effectiveness. It is therefore important to understand which PROs patients with rheumatic and musculoskeletal disease consider most important to track for disease management. Methods Adult US patients within the ArthritisPower registry with ankylosing spondylitis, fibromyalgia syndrome, osteoarthritis, osteoporosis, psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus were invited to select between 3 and 10 PRO symptom measures they felt were important to digitally track for their condition via the ArthritisPower app. Over the next 3 months, participants (pts) were given the option to continue tracking their previously selected measures or to remove/add measures at 3 subsequent monthly time points (month [m] 1, m2, m3). At m3, pts prioritized up to 5 measures. Measures were rank-ordered, summed, and weighted based on pts rating to produce a summary score for each PRO measure. Results Among pts who completed initial selection of PRO assessments at baseline (N = 253), 140 pts confirmed or changed PRO selections across m1–3 within the specified monthly time window (28 days ± 7). PROs ranked as most important for tracking were PROMIS Fatigue, Physical Function, Pain Intensity, Pain Interference, Duration of Morning Joint Stiffness, and Sleep Disturbance. Patient’s preferences regarding the importance of these PROs were stable over time. Conclusion The symptoms that rheumatology patients prioritized for longitudinal tracking using a smartphone app were fatigue, physical function, pain, and morning joint stiffness.

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Flow Cytometric Evaluation of the Ongoing Angiogenic Response in Rat Cardiac Tissue Following Myocardial Infarction

Current Protocols ◽

10.1002/cpz1.40 ◽

2021 ◽

Vol 1 (2) ◽

Author(s):

Cecilie Hoeeg ◽

Lars Ringgaard ◽

Esben Christensen ◽

Bjarke Follin ◽

Simon Bentsen ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Tissue ◽

Angiogenic Response ◽

Flow Cytometric ◽

Flow Cytometric Evaluation

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Hybrid fuzzy interface model of sports rehabilitation activities

Journal of Intelligent & Fuzzy Systems ◽

10.3233/jifs-219054 ◽

2021 ◽

pp. 1-10

Author(s):

Wu Shoujiang

Keyword(s):

Evaluation System ◽

Clustering Algorithm ◽

Mixed Model ◽

Expectation Maximization Algorithm ◽

Rehabilitation Training ◽

Development Platform ◽

Longitudinal Tracking ◽

Database Structure ◽

The Matrix ◽

Matrix Normal

At present, the relevant test data and training indicators of athletes during rehabilitation training lack screening and analysis, so it is impossible to establish a long-term longitudinal tracking research system and evaluation system. In order to improve the practical effect of sports rehabilitation activities, this paper successively introduces the matrix normal mixed model and the fuzzy clustering algorithm based on the K-L information entropy regularization and the matrix normal mixed model. Moreover, this paper uses the expectation maximization algorithm to estimate the parameters of the model, discusses the framework, key technologies and core services of the development platform, and conducts certain research on the related technologies of the three-tier architecture. At the same time, according to the actual needs of sports rehabilitation training, this paper designs the functions required for exercise detection and prescription formulation. In addition, this paper analyzes and designs the database structure involved in each subsystem. Finally, this paper designs experiments to verify the performance of the model constructed in this paper. The research results show that the performance of the model constructed in this paper meets the expectations of model construction, so it can be applied to practice.

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61892 Systemic TLR3-targeting Combinatorial Chemokine Modulation Sensitizes Murine Tumors to PD-1 Blockade

Journal of Clinical and Translational Science ◽

10.1017/cts.2021.444 ◽

2021 ◽

pp. 1-2

Author(s):

Kathleen M. Kokolus ◽

Nataša Obermajer ◽

Per Basse ◽

Pawel Kalinski

Keyword(s):

Murine Tumors

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Tracking Older Participants of Twelve Physical Activity Classes Over a Three-Year Period

Journal of Aging and Physical Activity ◽

10.1123/japa.6.1.70 ◽

1998 ◽

Vol 6 (1) ◽

pp. 70-82 ◽

Cited By ~ 33

Author(s):

Nancy A. Ecclestone ◽

Anita M. Myers ◽

Donald H. Paterson

Keyword(s):

Physical Activity ◽

Older Adults ◽

Exercise Adherence ◽

Attendance Rate ◽

Longitudinal Tracking ◽

Gender And Age ◽

Program Adherence ◽

Exercise Classes ◽

Physical Activity Classes

The Centre for Activity and Ageing offers multiple physical activity programs for the general public of older adults. Using a database of 670 registrants, we tracked 541 individuals in 12 programs at the same location over a 3-year period (1992-1995). We found program differences in gender and age mix, attendance patterns, and long-term adherence. Overall, we found a 68% attendance rate and adherence rates of 59%, 51%, and 43% at 6 months, 12 months, and 36 months, respectively. About 21% of participants tried out or transferred between programs during the tracking period, and these individuals were significantly more likely to remain at the center over 3 years. Longitudinal tracking demonstrates that program adherence is not necessarily the same as exercise adherence: older adults leave, rejoin, and switch exercise classes as their commitments and interests change. We project that 50% or more of older adults joining community programs will be long-term adherents to exercise.

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