Direct Reprogramming of Mouse Fibroblasts into Functional Skeletal Muscle Progenitors

Skeletal muscle harbors quiescent stem cells termed satellite cells and proliferative progenitors termed myoblasts, which play pivotal roles during muscle regeneration. However, current technology does not allow permanent capture of these cell populations in vitro. Here, we show that ectopic expression of the myogenic transcription factor MyoD, combined with exposure to small molecules, reprograms mouse fibroblasts into expandable induced myogenic progenitor cells (iMPCs). iMPCs express key skeletal muscle stem and progenitor cell markers including Pax7 and Myf5 and give rise to dystrophin-expressing myofibers upon transplantation in vivo. Notably, a subset of transplanted iMPCs maintain Pax7 expression and sustain serial regenerative responses. Similar to satellite cells, iMPCs originate from Pax7+ cells and require Pax7 itself for maintenance. Finally, we show that myogenic progenitor cell lines can be established from muscle tissue following small-molecule exposure alone. This study thus reports on a robust approach to derive expandable myogenic stem/progenitor-like cells from multiple cell types

BCR-ABL1–Negative Chronic Myeloproliferative Neoplasms and Pulmonary Hypertension: A Prospective Long-Term Follow-up Study of the Impact of Pulmonary Hypertension on Survival

This prospective study assessed the prevalence of pulmonary hypertension (PHT) related to chronic myeloproliferative neoplasms (CMPNs) and evaluated the impact of PHT on survival during long-term follow-up. In a large group of BCR-ABL1–negative CMPN patients, there was a low prevalence of PHT. The impact of PHT on survival was negligible. © 2020 Elsevier Inc.Purpose: To assess the prevalence of PHT in patients with BCR-ABL1–negative CMPN and to evaluate impact of PHT on survival during long-term follow-up. Patients and Methods: A total of 122 patients with BCR-ABL1–negative CMPN underwent transthoracic echocardiographic (TTE) evaluation at the beginning of study. Patients undergoing PHT on TTE examination were also evaluated by a pulmonologist. Patients were divided into 3 groups. Group A comprised patients with CMPN-related PHT; group B, patients with no PHT; and group C, patients with PHT due to secondary causes. Patients were evaluated again every 3 to 6 months. Results: PHT was detected in 33 (27%) of 122 patients. Eight (6.5%) had CMPN-related PHT and the remaining 25 (20.5%) had non–CMPN-related PHT. Positivity for JAK2 V617F mutation in the study population was 72.9%. Groups were similar with respect to hematologic parameters and gender. Follow-up times were as follows: median (range) time from diagnosis to TTE and study end were 34 (1-158) months and 107 (16-251) months, respectively, and from TTE to study end was 88 (7-110) months. No significant differences found among the groups in terms of median time from diagnosis to TTE, follow-up, and overall survival. Conclusion: BCR-ABL1–negative CMPN patients had a lower prevalence of PHT compared to earlier studies. There was no statistically significant difference in median overall survival between patients with or without PHT. This may be because patients with PHT were asymptomatic and PHT was mild. The impact of PHT on survival was negligible. © 2020 Elsevier Inc

Sinus node deceleration during exercise stress testing: Bezold-Jarisch reflex versus sinus node ischemia

PubMed ID: 15165957[No abstract available

PON1 activities and oxidative markers of LDL in patients with angiographic ally proven coronary artery disease

WOS: 000185423500006PubMed ID: 12957728Background: There is growing evidence that ox-LDL plays an important role during the atherosclerosis process and PON1 can significantly inhibit generation of lipid peroxidation during LDL oxidation and thus play a role in the in vivo protection by HDL against atherosclerosis. Methods: Twenty-four healthy volunteers and one-hundred and one patients were taken into study, sixty-eight patients had coronary artery disease which was confirmed by coronary angiography. Serum PON1, erythrocyte superoxide dismutase and catalase activities, oxidative markers of LDL were determined along with the routine biochemical parameters in all groups. Results: The indicators of oxidative stress were higher in the patients compared with the controls. No statistically significant difference in any of parameters were observed between the patients who had obstruction with different degrees except for erythrocyte TBARS [24.5 nmol/g Hb in patients with one vessel disease (VD) (n=22), 29.6 nmol/g Hb in patients with two VD (n=26) and 33.5 nmol/g Hb in patients with three VD (n=20)]. Basal and stimulated diene levels were higher in patients who had more diseased vessels than those who had less. Conclusion: The increase in erythrocyte TBARS and CRP levels with the severity of disease supports the reports that showed the inflammatory and oxidative nature of atherosclerosis. In the light of the fact that the well-known classical risk factors for atherosclerosis are closely associated with increased oxidative stress, we propose that the elevation in TBARS levels might be a more marked indicator for the degree of atherosclerosis than the insufficiency in antioxidant enzymes such as SOD and PON1. (C) 2003 Elsevier Ireland Ltd. All rights reserved

Effects of home-based cardiac exercise program on the exercise tolerance, serum lipid values and self-efficacy of coronary patients

Exercise-based cardiac rehabilitation improves exercise capacity and reduces cardiac risk factors. The purpose of this pilot study was to examine the effects of a home-based cardiac exercise program (HBCEP) on exercise tolerance, serum lipids, and self-efficacy in coronary heart disease patients in Turkey. Self-efficacy theory provided the framework for this study's intervention. The study design was a pre-test and post-test experimental, randomized assignment. The study included 30 participants in a home-based cardiac exercise program (HBCEP; mean age = 54.7 ± 7.8) and 30 in control (C; mean age = 52.7 ± 6.5). The Phase II cardiac exercise program included three 45-60-min sessions per week for 12 weeks, and the enhancement of self-efficacy through educational sessions and the use of goal setting, modelling, and physiological feedback strategies. Both groups were comparable in their medical regimen, exercise capacity, and other measured variables pre-intervention. At baseline and after 12 weeks, exercise capacity was evaluated by exercise testing using the Bruce Protocol, self-efficacy was measured with the Cardiac Exercise Self Efficacy Index, and serum lipid values were measured. At the completion of the 12-week exercise program, the exercise capacity (P<0.001), total cholesterol (P =0.004), triglycerides (P = 0.048), high-density lipoprotein-cholesterol (P = 0.001), low-density lipoprotein-cholesterol (P = 0.039), and self-efficacy (P<0.001) of the HBCEP Group were significantly improved compared to the control group. These results suggest that a first-time HBCEP in Turkey can be successful in having patients adhere to a prescribed exercise program and reduce risk factors. Enhanced self-efficacy may have mediated the improved behavioural outcomes. © 2006, European Society of Cardiology. All rights reserved

Long-term follow-up in patients with homozygous familial hypercholesterolemia; 13-year experience of a university hospital lipid clinic [Homozigot ailevi hiperkolesterolemili hastalarin uzun dönem izlemi: Bir üniversite hastanesi lipit poliklini?inin 13 yillik deneyimi]

PubMed ID: 25490294Objectives: Familiar hypercholesterolemia (FH) is a genetic disease characterized with extremely high levels of cholesterol leading to premature atherosclerosis. In homozygous individuals (HoFH) cardiovascular events could develop in childhood. In this article, long-term clinical experience with adult HoFH patients who are followed in Department of Cardiology, Ege University Faculty of Medicine is presented. Study design: Seventeen HoFH patients (11 females, 6 males) who are being followed between the years 2000-2013 were included. All data including clinical characteristics, family history, lipid levels, treatment, lipid-apheresis, cardiovascular events, complications were obtained retrospectively from patient chart records. Results: Mean age was 31 ±10 years at admission to our clinic. First diagnosis age was 25±14. At diagnosis, mean cholesterol level was 625±136 mg/dl. Admission complaints were dermatologic (41 %) and ischemic symptoms (41 %). Atotal of 3 patients (18%) were diagnosed during family screening. 65% of the patients' parents had consanguineous marriage. Xantomas was present in 59%, aortic valve pathology in 59%, and carotid artery plaques in 47%. Coronary artery disease was documented in 59%. Though all patients had indication for apheresis, 10 patients received apheresis due to high refusal rate. Age at the first apheresis was 27±12 (minimum 10-maximum 42) and adherence to apheresis was 60%. With 2 years regular apheresis skin depositions were vanished, however carotid atherosclerosis and aortic pathology progressed. During the 43±42 months follow-up, 4 patients died (mean age: 25±5). Conclusion: Diagnosis is late in HoAH. Due to the delayed treatment of lipid apheresis, atherosclerosis and aortic stenosis progress in these patients. The awareness of the physicians and knowledge of the public is warranted. © 2014 Turkish Society of Cardiology