scholarly journals Unravelling the Biology of Adult Cardiac Stem Cell-Derived Exosomes to Foster Endogenous Cardiac Regeneration and Repair

2020 ◽  
Vol 21 (10) ◽  
pp. 3725 ◽  
Author(s):  
Teresa Mancuso ◽  
Antonella Barone ◽  
Alessandro Salatino ◽  
Claudia Molinaro ◽  
Fabiola Marino ◽  
...  
Keyword(s):  
Myogenic Differentiation ◽  
Cardiac Regeneration ◽  
Heart Tissue ◽  
Fate Map ◽  
Cardiac Muscle Cells ◽  
Paracrine Effects ◽  
Cell Therapies ◽  
Adult Heart ◽  
Beneficial Effects

Cardiac remuscularization has been the stated goal of the field of regenerative cardiology since its inception. Along with the refreshment of lost and dysfunctional cardiac muscle cells, the field of cell therapy has expanded in scope encompassing also the potential of the injected cells as cardioprotective and cardio-reparative agents for cardiovascular diseases. The latter has been the result of the findings that cell therapies so far tested in clinical trials exert their beneficial effects through paracrine mechanisms acting on the endogenous myocardial reparative/regenerative potential. The endogenous regenerative potential of the adult heart is still highly debated. While it has been widely accepted that adult cardiomyocytes (CMs) are renewed throughout life either in response to wear and tear and after injury, the rate and origin of this phenomenon are yet to be clarified. The adult heart harbors resident cardiac/stem progenitor cells (CSCs/CPCs), whose discovery and characterization were initially sufficient to explain CM renewal in response to physiological and pathological stresses, when also considering that adult CMs are terminally differentiated cells. The role of CSCs in CM formation in the adult heart has been however questioned by some recent genetic fate map studies, which have been proved to have serious limitations. Nevertheless, uncontested evidence shows that clonal CSCs are effective transplantable regenerative agents either for their direct myogenic differentiation and for their paracrine effects in the allogeneic setting. In particular, the paracrine potential of CSCs has been the focus of the recent investigation, whereby CSC-derived exosomes appear to harbor relevant regenerative and reparative signals underlying the beneficial effects of CSC transplantation. This review focuses on recent advances in our knowledge about the biological role of exosomes in heart tissue homeostasis and repair with the idea to use them as tools for new therapeutic biotechnologies for “cell-less” effective cardiac regeneration approaches.

Inhibin alpha- and beta A-subunit immunoreactivity in the chicken embryo during morphogenesis

Development ◽  
1992 ◽  
Vol 115 (4) ◽  
pp. 1079-1086
Author(s):  
M. Blauer ◽  
J. Kohonen ◽  
I. Leivonen ◽  
P. Vilja ◽  
P. Tuohimaa
Keyword(s):  
Cardiac Muscle ◽  
Bone Morphogenetic Proteins ◽  
Myogenic Differentiation ◽  
Muscle Cells ◽  
Amino Acid Sequences ◽  
Alpha Subunit ◽  
Cardiac Muscle Cells ◽  
Immunoreactive Protein ◽  
A Subunit

Antibodies against synthetic peptides selected from the amino acid sequences of human inhibin alpha- and beta A-subunits were used to examine the distribution of inhibin subunit immunoreactivity in chicken embryos during the first week of development. Inhibin alpha-subunit immunoreactivity was localized in skeletal and smooth muscle myoblasts as well as developing cardiac muscle cells. In somites, immunostaining was seen exclusively in myotomes. The appearance of alpha-subunit immunoreactivity was correlated with myogenic differentiation; immunoreactivity was not seen in non-differentiated mesenchymal cells or in terminally differentiated adult muscle cells. In cardiac muscle, some immunopositive myocytes were seen also in the adult. In the adult heart, the Purkinje fibers were strongly immunoreactive, suggesting a possible role of the immunoreactive protein in the impulse-conducting function of these specialized cells. Inhibin alpha-subunit immunoreactivity was also seen in the visceral and parietal cells of the Bowman's capsule in both mesonephric and metanephric kidneys. In addition to mesodermal derivatives, alpha-subunit immunoreactivity was localized in neuroepithelial cells and axons in the developing central nervous system. Immunoblotting with anti-alpha(1–32) revealed two protein bands with M(r) values of 50,000 and 32,000 in cytosol samples of whole embryos under nonreducing conditions. In reduced samples an approximately 14,000 M(r) protein species was detected. Inhibin beta A-subunit immunoreactivity was detected only in chondrocytes, suggesting that the immunoreactive protein might represent a chicken homologue of the various cartilage and bone morphogenetic proteins expressed in mammals.

Abstract 32: The Role of Cyclin A2 in Adult Human Cardiomyocyte Plasticity

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Amaresh Ranjan ◽  
Sangeetha Vadakke Madathil ◽  
Hina Chaudhry
Keyword(s):  
Cardiac Regeneration ◽  
Time Lapse ◽  
Heart Tissue ◽  
Functional Restoration ◽  
Epifluorescence Microscopy ◽  
Cardiac Marker ◽  
Human Cardiomyocytes ◽  
Adult Human ◽  
Cyclin A2

The adult mammalian heart is known to have a very low abundance of progenitor cells which can take part in active cycling and regeneration after damage. Cardiomyocytes exit the cell cycle soon after birth coincident with the silencing of cyclin A2 (CCNA2). In our previous studies, we demonstrated that viral delivery of Ccna2 induces cardiac regeneration in infarcted hearts of small and large animal models. However, the molecular mechanism whereby Ccna2 induces cardiac regeneration and increase in cardiac function deserves further study. To explore further, we isolated adult mouse cardiomyocytes and induced Ccna2 expression by using adenovirus transfection and cultured them for 3 weeks. Co-expression of the mature cardiac marker troponin Tc with the immature cardiac marker non-muscle myosin IIB was observed. Additionally, expression of epithelial to mesenchymal transition markers (vimentin and FSP1) was observed. Also, decreased expression of mature cardiac markers α-MHC , ckmt2 and cTnT was noted. To study the factors responsible for human cardiomyocyte plasticity and cell division, we have optimized a novel method for culturing adult human cardiomyocytes in our laboratory. We cultured cardiomyocytes isolated from heart tissue obtained from a 55 yr old male patient. After transfection with CCNA2 adenovirus made for human use (cTnT promoter driving human CCNA2 cDNA), they were co-transfected with two more adenoviruses (1) cTnT-GFP to label cardiomyocytes (green) and (2) CMV-α-actinin-m-Cherry to label the sarcomere (red). Time lapse live epifluorescence microscopy was carried out for 70 hrs and time lapse movies were prepared (please refer the youtube link to see a representative time lapse movie https://youtu.be/OBrJGCq7YCA ). Movies were analyzed to calculate the cytokinesis index in samples transfected with (Test) and without (Null) CCNA2 adenoviruses. We observed a significantly higher cytokinesis index in CCNA2 samples versus Null. We are further investigating the role of cyclin A2 in dedifferentiation of adult human cardiomyocytes to generate immature or progenitor cardiac cells and their contractile status, which could be utilized for regeneration and functional restoration of damaged adult heart tissue.

Review of Constipation Treatment Methods with Emphasis on Laxative Foods

2020 ◽  
Vol 16 (5) ◽  
pp. 675-688
Author(s):  
Shamsi Abbasalizadeh ◽  
Behzad Ebrahimi ◽  
Aslan Azizi ◽  
Rogaye Dargahi ◽  
Maryam Tayebali ◽  
...  
Keyword(s):  
Well Being ◽  
Health Concern ◽  
Lifestyle Factor ◽  
Flax Seed ◽  
Lifestyle Modifications ◽  
Food Ingredients ◽  
Beneficial Effects ◽  
Daily Exercise

Constipation is a common public health concern experienced by all individuals during their life affecting the quality of life. In this paper, we aimed to provide an overview of the existing evidence regarding the role of food ingredients, including bran, prune, fig, kiwifruit, and flax-seed in constipation treatment. We searched Scopus, Pub Med, and Science Direct by using the keywords, “laxative foods” and “constipation”, for searching studies assessing laxative food ingredients and their beneficial effects on constipation treatment and/or control. Lifestyle modifications such as increasing dietary fiber and fluid intake and daily exercise are the proposed first line treatments for constipation. Optimizing ‘diet’ as an efficient lifestyle factor may contribute to the well-being of patients. The use of laxative food ingredients including bran, prune, fig, kiwifruit, flax-seed, probiotics, and prebiotics is a convenient alternative to cope with constipation. According to previous findings, laxative food ingredients could be considered as effective treatments for subjects suffering from constipation. Many studies have assessed the pharmacological and non-pharmacological roles of these ingredients in treating constipation, however, their importance has not been thoroughly investigated.

Dietary Carotenoids in Managing Metabolic Syndrome and Role of PPARs in the Process

2020 ◽  
Vol 16 (6) ◽  
pp. 846-853
Author(s):  
Raghunandan Purohith ◽  
Nagendra P.M. Nagalingaswamy ◽  
Nanjunda S. Shivananju
Keyword(s):  
Metabolic Syndrome ◽  
Dietary Intervention ◽  
Bioactive Constituents ◽  
Dietary Antioxidants ◽  
Predisposing Factor ◽  
Beneficial Effects ◽  
Pathological Conditions ◽  
Established Relationship ◽  
Comprehensive Study

Metabolic syndrome is a collective term that denotes disorder in metabolism, symptoms of which include hyperglycemia, hyperlipidemia, hypertension, and endothelial dysfunction. Diet is a major predisposing factor in the development of metabolic syndrome, and dietary intervention is necessary for both prevention and management. The bioactive constituents of food play a key role in this process. Micronutrients such as vitamins, carotenoids, amino acids, flavonoids, minerals, and aromatic pigment molecules found in fruits, vegetables, spices, and condiments are known to have beneficial effects in preventing and managing metabolic syndrome. There exists a well-established relationship between oxidative stress and major pathological conditions such as inflammation, metabolic syndrome, and cancer. Consequently, dietary antioxidants are implicated in the remediation of these complications. The mechanism of action and targets of dietary antioxidants as well as their effects on related pathways are being extensively studied and elucidated in recent times. This review attempts a comprehensive study of the role of dietary carotenoids in alleviating metabolic syndromewith an emphasis on molecular mechanism-in the light of recent advances.

Endometrial Regeneration in Asherman's Syndrome: Clinical and Translational evidence of Stem Cell Therapies

2019 ◽  
Vol 14 (6) ◽  
pp. 454-459
Author(s):  
Xuejing Hou ◽  
Ying Liu ◽  
Isabelle Streuli ◽  
Patrick Dällenbach ◽  
Jean Dubuisson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Molecular Mechanisms ◽  
Uterine Cavity ◽  
Stem Cell Therapies ◽  
Intrauterine Adhesions ◽  
Asherman’S Syndrome ◽  
Cell Therapies ◽  
Fibrotic Process ◽  
Physical Barriers

Asherman’s Syndrome or Intrauterine adhesions is an acquired uterine condition where fibrous scarring forms within the uterine cavity, resulting in reduced menstrual flow, pelvic pain and infertility. Until recently, the molecular mechanisms leading to the formation of fibrosis were poorly understood, and the treatment of Asherman’s syndrome has largely focused on hysteroscopic resection of adhesions, hormonal therapy, and physical barriers. Numerous studies have begun exploring the molecular mechanisms behind the fibrotic process underlying Asherman’s Syndrome as well as the role of stem cells in the regeneration of the endometrium as a treatment modality. The present review offers a summary of available stem cell-based regeneration studies, as well as highlighting current gaps in research.

Short-Term Ultramicronized Palmitoylethanolamide Therapy in Patients with Myasthenia Gravis: a Pilot Study to Possible Future Implications of Treatment

2019 ◽  
Vol 18 (3) ◽  
pp. 232-238 ◽  
Author(s):  
Emanuela Onesti ◽  
Vittorio Frasca ◽  
Marco Ceccanti ◽  
Giorgio Tartaglia ◽  
Maria Cristina Gori ◽  
...  
Keyword(s):  
Pilot Study ◽  
Myasthenia Gravis ◽  
Repetitive Nerve Stimulation ◽  
Beneficial Effects ◽  
Antibody Titers ◽  
The Stability ◽  
Ultramicronized Palmitoylethanolamide ◽  
Open Pilot

Background: The cannabinoid system may be involved in the humoral mechanisms at the neuromuscular junction. Ultramicronized-palmitoylethanolamide (μm-PEA) has recently been shown to reduce the desensitization of Acetylcholine (ACh)-evoked currents in denervated patients modifying the stability of ACh receptor (AChR) function. <p> Objective: To analyze the possible beneficial effects of μm-PEA in patients with myasthenia gravis (MG) on muscular fatigue and neurophysiological changes. <p> Method: The duration of this open pilot study, which included an intra-individual control, was three weeks. Each patient was assigned to a 1-week treatment period with μm-PEA 600 mg twice a day. A neurophysiological examination based on repetitive nerve stimulation (RNS) of the masseteric and the axillary nerves was performed, and the quantitative MG (QMG) score was calculated in 22 MG patients every week in a three-week follow-up period. AChR antibody titer was investigated to analyze a possible immunomodulatory effect of PEA in MG patients. <p> Results: PEA had a significant effect on the QMG score (p=0.03418) and on RNS of the masseteric nerve (p=0.01763), thus indicating that PEA reduces the level of disability and decremental muscle response. Antibody titers did not change significantly after treatment. <p> Conclusion: According to our observations, μm-PEA as an add-on therapy could improve muscular response to fatigue in MG. The possible modulation of AChR currents as a means of eliciting a direct effect from PEA on the conformation of ACh receptors should be investigated. The co-role of cytokines also warrants an analysis. Given the rapidity and reversibility of the response, we suppose that PEA acts directly on AChR, though further studies are needed to confirm this hypothesis.

The Role of Personal Control in Adaptive Functioning

2009 ◽  
pp. 270-278 ◽  
Author(s):  
Suzanne C. Thompson
Keyword(s):  
Ethnic Differences ◽  
Perceived Control ◽  
Adaptive Functioning ◽  
Coping Skills ◽  
Personal Control ◽  
Future Research ◽  
Sense Of Control ◽  
Beneficial Effects ◽  
Controllable Factors

A sense of personal control is an important resource that helps people maintain emotional stability and successfully negotiate their way through life. People foster their perceived control by focusing on reachable goals, creating new avenues for control, and accepting difficult-to-change circumstances. In general, perceived control need not be realistic in order to have beneficial effects, although in the area of health promotion, overestimating one's control can reduce the motivation to engage in protection. Research on ethnic differences in the benefits of a sense of personal control suggests that those from more collectivistic cultures or subcultures may be less benefited by a sense of personal control, relying instead on a socially derived sense of control. Successful interventions to enhance personal control include programs that bolster coping skills, give options and decisions to participants, and provide training that encourages attributions to controllable factors. Future research should further explore ethnic differences in the effects of personal control, the consequences of unrealistic control perceptions, and interventions to enhance the sense of control.

scholarly journals Physical Exercise and Cardiac Repair: The Potential Role of Nitric Oxide in Boosting Stem Cell Regenerative Biology

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1002
Author(s):  
Fabiola Marino ◽  
Mariangela Scalise ◽  
Eleonora Cianflone ◽  
Luca Salerno ◽  
Donato Cappetta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Stem Cell ◽  
Physical Exercise ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Heart Function ◽  
Stem Cell Biology ◽  
Myocardial Repair ◽  
Beneficial Effects

Over the years strong evidence has been accumulated showing that aerobic physical exercise exerts beneficial effects on the prevention and reduction of cardiovascular risk. Exercise in healthy subjects fosters physiological remodeling of the adult heart. Concurrently, physical training can significantly slow-down or even reverse the maladaptive pathologic cardiac remodeling in cardiac diseases, improving heart function. The underlying cellular and molecular mechanisms of the beneficial effects of physical exercise on the heart are still a subject of intensive study. Aerobic activity increases cardiovascular nitric oxide (NO) released mainly through nitric oxidase synthase 3 activity, promoting endothelium-dependent vasodilation, reducing vascular resistance, and lowering blood pressure. On the reverse, an imbalance between increasing free radical production and decreased NO generation characterizes pathologic remodeling, which has been termed the “nitroso-redox imbalance”. Besides these classical evidence on the role of NO in cardiac physiology and pathology, accumulating data show that NO regulate different aspects of stem cell biology, including survival, proliferation, migration, differentiation, and secretion of pro-regenerative factors. Concurrently, it has been shown that physical exercise generates physiological remodeling while antagonizes pathologic remodeling also by fostering cardiac regeneration, including new cardiomyocyte formation. This review is therefore focused on the possible link between physical exercise, NO, and stem cell biology in the cardiac regenerative/reparative response to physiological or pathological load. Cellular and molecular mechanisms that generate an exercise-induced cardioprotective phenotype are discussed in regards with myocardial repair and regeneration. Aerobic training can benefit cells implicated in cardiovascular homeostasis and response to damage by NO-mediated pathways that protect stem cells in the hostile environment, enhance their activation and differentiation and, in turn, translate to more efficient myocardial tissue regeneration. Moreover, stem cell preconditioning by and/or local potentiation of NO signaling can be envisioned as promising approaches to improve the post-transplantation stem cell survival and the efficacy of cardiac stem cell therapy.

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