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Ischemic heart disease is among the primary causes of cardiovascular-related deaths worldwide. Conventional treatments including surgical interventions and medical therapies aid in preventing further damage to heart muscle but are unable to provide a permanent solution. In recent years, stem cell therapy has emerged as an attractive alternative to restore damaged myocardium after myocardial injury. Allogeneic (donor-derived) mesenchymal stem cells (MSCs) have shown great promise in preclinical and clinical studies, making them the most widely accepted candidates for cardiac cell therapy. MSCs promote cardiac repair by modulating host immune system and secreting various soluble factors, of which prostaglandin E2 (PGE2) is an important one. PGE2 plays a significant role in regulating cardiac remodeling following myocardial injury. In this review, we provide an overview of allogeneic MSCs as candidates for myocardial regeneration with a focus on the role of the PGE2/cyclooxygenase-2 (COX2) pathway in mediating these effects. Key words: mesenchymal stem cells, COX2, PGE2, cardiac ischemia, immunoprivilege, cell therapy. La maladie cardiaque ischemique est parmi les principales causes de deces liees au systeme cardiovasculaire a l'echelle mondiale. Les traitements classiques, y compris les interventions chirurgicales et les traitements medicaux, contribuent a la prevention de plus de dommages au muscle cardiaque, mais ne sont pas en mesure de fournir une solution definitive. Au cours des dernieres annees, le traitement par les cellules souches s'est revele constituer un autre choix attrayant pour le retablissement du myocarde endommage a la suite de lesions myocardiques. Les cellules souches mesenchymateuses (CSM) allogeniques (issues de donneurs) se sont revelees tres prometteuses dans les etudes precliniques et cliniques, ce qui en a fait les candidates les plus largement acceptees pour la therapie cellulaire cardiaque. Les CSM favorisent la reparation du creur par l'intermediaire de la modulation du systeme immunitaire de l'hote et la secretion de divers facteurs solubles, dont la PGE2 est l'une des plus importantes. La PGE2 joue un role important dans la regulation du remodelage du creur a la suite de lesions cardiaques. Dans cet article de synthese, nous of frons un aperqu des CSM allogeniques en tant que candidates pour la regenerescence du myocarde, avec une attention particuliere sur le role de la voie de signalisation PGE2/COX2 dans la mediation de ces effets. [Traduit par la Redaction] Mots-cles: cellules souches mesenchymateuses, COX2, PGE2, ischemie cardiaque, immunoprivilege, therapie cellulaire., Introduction Cardiovascular diseases are the leading cause of deaths around the globe, consuming nearly 17.9 million lives annually (World Health Organization 2017). In Canada alone, these deaths account for almost [...]

Cardiac disorders remain the leading cause of mortality worldwide. Current clinical strategies, including drug therapy, surgical interventions, and organ transplantation offer limited benefits to patients without regenerating the damaged myocardium. Over the past decade, stem cell therapy has generated a keen interest owing to its unique self-renewal and immune privileged characteristics. Furthermore, the ability of stem cells to differentiate into specialized cell types, has made them a popular therapeutic tool against various diseases. This comprehensive review provides an overview of therapeutic potential of different types of stem cells in reference to cardiovascular diseases. Furthermore, it sheds light on the advantages and limitations associated with each cell type. An in-depth analysis of the challenges associated with stem cell research and the hurdles for its clinical translation and their possible solutions have also been elaborated upon. It examines the controversies surrounding embryonic stem cells and the emergence of alternative approaches, such as the use of induced pluripotent stem cells for cardiac therapeutic applications. Overall, this review serves as a valuable resource for researchers, clinicians, and policymakers involved in the field of regenerative medicine, guiding the development of safe and effective stem cell-based therapies to revolutionize patient care. [ABSTRACT FROM AUTHOR]

Increasing reports of successful and safe application of bone marrow derived mesenchymal stem cells (BM-MSCs) for cell therapy are pouring in from numerous studies. However poor survival of transplanted cells in the recipient has impaired the benefits of BM-MSCs based therapies. Therefore cell product preparation procedures pertaining to MSC therapy need to be optimized to improve the survival of transplanted cells. One of the important ex vivo procedures in the preparation of cells for therapy is passaging of BM-MSCs to ensure a suitable number of cells for transplantation, which may affect the turnover of proteins involved in regulation of cell survival and (or) death pathways. In the current study, we investigated the effect of an increase in passage number of BM-MSCs in cell culture on the intracellular protein turnover (protein synthesis, processing, and degradation machinery). We performed proteomic analysis of BM-MSCs at different passages. There was no significant difference observed in the ribosomal, protein processing, and proteasomal pathways related proteins in BM-MSCs with an increase in passage number from P3 to P7. Therefore, expansion of MSCs in the cell culture in clinically relevant passages (Passage 3-7) does not affect the quality of MSCs in terms of intracellular protein synthesis and turnover. Key words: mesenchymal stem cells, transplantation, regenerative therapy, proteomic analysis. De plus en plus de rapports de succes de l'application securitaire de cellules souches mesenchymateuses (CSM) issues de la moelle osseuse a la therapie cellulaire affluent de nombreuses etudes. Cependant, les bienfaits tires des therapies a base de CSM sont voiles par la mauvaise survie des cellules greffees chez le receveur. Par consequent, il convient d'optimiser les procedures de preparation de produits cellulaires afferents a la therapie par les CSM en vue d'ameliorer la survie des cellules greffees. Le repiquage des CSM represente une importante procedure de preparation ex vivo des cellules servant aux traitements dans le but de s'assurer de la presence d'un nombre approprie de cellules pour la greffe. Toutefois, cette procedure peut entrainer des modifications dans le <> des proteines jouant un role dans la regulation des voies de signalisation de la survie ou de la mort cellulaires. Dans les presents travaux, nous avons etudie l'effet de l'augmentation du nombre de repiquages de CSM en culture cellulaire sur le << turnover >>intracellulaire des proteines (rouages de leur synthese, de leur traitement et de leur degradation). Nous avons effectue une analyse proteomique des CSM lors de differents repiquages. Lors de l'augmentation du nombre de cellules repiquees entre P3 et P7, nous n'avons observe aucune difference notable quant aux proteines liees aux voies de signalisation des proteases ainsi que du traitement ribosomal et des proteines dans les CSM. Par consequent, l'expansion des CSM en culture cellulaire par les repiquages cliniquement significatifs (repiquages 3 a 7) n'a pas d'effet qualitatif sur les CSM en matiere de synthese et de <> des proteines intracellulaires. [Traduit par la Redaction] Mots-cles: cellules souches mesenchymateuses, greffe, therapie regeneratrice, analyse proteomique., Introduction Mesenchymal stem cells (MSCs) form 0.01%-0.001% of the stromal population from bone marrow (BM) (Mendez-Ferrer et al. 2010). These cells have the characteristics of being plastic adherent, spindle shaped, [...]

MXene QDs (MQDs) have been effectively used in several fields of biomedical research. Considering the role of hyperactivation of immune system in infectious diseases, especially in COVID‐19, MQDs stand as a potential candidate as a nanotherapeutic against viral infections. However, the efficacy of MQDs against SARS‐CoV‐2 infection has not been tested yet. In this study, Ti3C2 MQDs are synthesized and their potential in mitigating SARS‐CoV‐2 infection is investigated. Physicochemical characterization suggests that MQDs are enriched with abundance of bioactive functional groups such as oxygen, hydrogen, fluorine, and chlorine groups as well as surface titanium oxides. The efficacy of MQDs is tested in VeroE6 cells infected with SARS‐CoV‐2. These data demonstrate that the treatment with MQDs is able to mitigate multiplication of virus particles, only at very low doses such as 0,15 µg mL−1. Furthermore, to understand the mechanisms of MQD‐mediated anti‐COVID properties, global proteomics analysis are performed and determined differentially expressed proteins between MQD‐treated and untreated cells. Data reveal that MQDs interfere with the viral life cycle through different mechanisms including the Ca2+ signaling pathway, IFN‐α response, virus internalization, replication, and translation. These findings suggest that MQDs can be employed to develop future immunoengineering‐based nanotherapeutics strategies against SARS‐CoV‐2 and other viral infections. [ABSTRACT FROM AUTHOR]

Cardiac injury and loss of cardiomyocytes is a causative as well as a resultant condition of cardiovascular disorders, which are the leading cause of death throughout the world. This loss of cardiomyocytes cannot be completely addressed through the currently available drugs being administered, which mainly function only in relieving the symptoms. There is a huge potential being investigated for regenerative and cell replacement therapies through recruiting stem cells of various origins namely embryonic, reprogramming/induction, and adult tissue. These sources are being actively studied for translation to clinical scenarios. In this review, we attempt to discuss some of these promising scenarios, including the clinical trials and the obstacles that need to be overcome, and hope to address the direction in which stem cell therapy is heading. Key words: stem cell therapy, cardiac regeneration, cardiomyocytes, heart failure, reprogramming. Les lesions cardiaques et la perte de cardiomyocytes sont les causes autant que les resultantes des maladies cardiovasculaires, la principale cause de deces a l'echelle mondiale. Les medicaments actuels ne suffisent pas a enrayer cette perte de cardiomyocytes : leurs effets se limitent presque exclusivement a l'attenuation des symptomes. Les traitements de regenerescence et de remplacement des cellules par le recrutement de cellules souches d'origines diverses (embryonnaire, reprogrammation-induction et tissu adulte) sont tres prometteurs et font actuellement l'objet de recherches. Ces sources de cellules souches sont etudiees activement en vue de les faire passer au domaine clinique. Dans le present article de synthese, nous tentons de discuter de certains de ces traitements prometteurs, des essais cliniques a mener et des obstacles a surmonter, et abordons l'orientation que prend l'usage therapeutique des cellules souches. [Traduit par la Redaction] Mots-cles: usage therapeutique des cellules souches, regenerescence cardiaque, cardiomyocytes, insuffisance cardiaque, reprogrammation., Introduction There are scores of pharmacological interventions available to deal with the complexities associated with or leading to myocardial infarction (MI), which is a major affliction globally (Gaziano et al. [...]

Doxorubicin (Dox) is frequently used as a frontline chemotherapeutic agent against a variety of cancers. Tremendous progress has been made on its optimal usage over the last 40 years. However, cardiotoxicity still remains a major concern. The great promise in this matter is that the mechanisms leading to antitumor activity appear to be different from those leading to Dox-induced cardiomyopathy. In this regard, various cardioprotective agents have been discussed. Attention should be drawn to probucol, a lipid-lowering agent with potent antioxidant properties, which provides complete protection against Dox-induced cardiomyopathy in rats without interfering with the antitumor properties of Dox in an experimental setting. Clinical trials employing Dox therapy in combination with probucol are needed to determine whether the outstanding findings in animal experiments can be extrapolated to clinical results. We have much further to go before the establishment of cancer therapies without any risk of cardiac side effects. Key words: congestive heart failure, antioxidants, oxidative stress. Resume : La doxorubicine (Dox) est frequemment utiliseee comme agent chimiotherapique de premiere ligne de soins dans le traitement de certains cancers. Meme si au cours de 40 dernieres annees on a realise d'enormes progres dans l'utilisation optimale de cet agent, sa cardiotoxicite demeure un probleme important. Cependant, le mecanisme responsable de l'action antitumorale semble different de celui a la base de la cardiomyopathie induite par la Dox. A cette fin, divers agents cardioprotecteurs ont ete etudies. On devrait porter une attention particuliere au probucol, un agent hypolipidemiant aux proprietes antioxydantes qui, chez des rats dans un contexte experimental, procure une protection complete contre la cardiomyopathie induite par la Dox tout en n'entravant pas les proprietes antitumorales. Des essais cliniques combinant le traitement therapeutique au Dox et au probucol sont neecessaires pour determiner si ces observations de premiere importance dans des etudes animales se transposent dans un contexte clinique. Il y a encore beaucoup de travail a faire avant d'etre en mesure d'offrir des traitements therapeutiques du cancer ne presentant aucun effet secondaire sur le coeur. Mots-cles: insuffisance cardiaque congestive, antioxydants, stress oxydatif. [Traduit par la Redaction], Introduction Doxorubicin (Dox) was introduced in cancer therapy in the late 1960s. It has emerged as one of the most potent broad-spectrum antitumor anthracycline antibiotics. Dox can be administered as [...]

It is known that TNF-[alpha] increases the production of ROS and decreases antioxidant enzymes, resulting in an increase in oxidative stress. IL-10 appears to modulate these effects. The present study investigated the role of p38 and ERK1/2 MAPKs in mediating the interplay of TNF-[alpha] and IL-10 in regulating oxidative stress and cardiac myocyte apoptosis in Sprague-Dawley male rats. Isolated adult cardiac myocytes were exposed to TNF-[alpha] (10 ng/ml), IL-10 (10 ng/ml), and IL-10 + TNF-[alpha] (ratio 1) for 4 h. [H.sub.2][O.sub.2] (100 [micro]M) as a positive control and the antioxidant Trolox (20 [micro]mol/l) were used to confirm the involvement of oxidative stress. [H.sub.2][O.sub.2] treatment increased oxidative stress and apoptosis; TNF-[alpha] mimicked these effects. Exposure to TNF-[alpha] significantly increased ROS production, caused cell injury, and increased the number of apoptotic cells and Bax-to-Bcl-xl ratio. This change was associated with an increase in the phospho-p38 MAPK-to-total p38 MAPK ratio and a decrease in the phospho-ERK1/2-to-total ERK1/2 ratio. IL-10 treatment by itself had no effect on these parameters, but it prevented the above-listed changes caused by TNF-[alpha]. The antioxidant Trolox modulated TNF-[alpha]-induced changes in Bax/Bcl-xl, cell injury, and MAPKs. Preexposure of cells to the p38 MAPK inhibitor SB-203580 prevented TNF-[alpha]-induced changes. Inhibition of the ERK pathway with PD-98059 attenuated the protective role of IL-10 against TNF-[alpha]-induced apoptosis. This study provides evidence in support of the essential role of p38 and ERK1/2 MAPKs in the interactive role of TNF-[alpha] and IL-10 in cardiac myocyte apoptosis. cell communication; heart failure: mitogen-activated protein kinase; signal transduction

Abstract: The present study examines whether a subchronic probucol treatment of rats offers protection against ischemia-reperfusion JR) injury in isolated perfused hearts. Sprague-Dawley rats were treated every second day per [...]

Integration of 2D structures into other low‐dimensional materials results in the development of distinct van der Waals heterostructures (vdWHSs) with enhanced properties. However, obtaining 2D–1D–0D vdWHSs of technologically useful next generation materials, transition‐metal carbide MXene and monoelemental Xene nanosheets in a single superlattice heterostructure is still challenging. Here, the fabrication of a new multidimensional superlattice heterostructure "GerMXene" from exfoliated M3X2Tx MXene and hydrogenated germanane (GeH) crystals, is reported. Direct experimental evidence for conversion of hydrothermally activated titanium carbide MXene (A‐MXene) to GerMXene heterostructure through the rapid and spontaneous formation of titanium germanide (TiGe2 and Ti6Ge5) bonds, is provided. The obtained GerMXene heterostructure possesses enhanced surface properties, aqueous dispersibility, and Dirac signature of embedded GeH nanosheets as well as quantum dots. GerMXene exhibits functional bioactivity, electrical conductivity, and negative surface charge, paving ways for its applications in biomedical field, electronics, and energy storage. [ABSTRACT FROM AUTHOR]

MXene nanomaterials have sparked significant interest among interdisciplinary researchers to tackle today's medical challenges. In particular, colloidal MXene quantum dots (MQDs) offer the high specific surface area and compositional flexibility of MXene while providing improvements to aqueous stability and material–cell interactions. The current study for the first time reports the development and application of immunoengineered tantalum‐carbide (Ta4C3Tx) MQDs for in vivo treatment of transplant vasculopathy. This report comes at a critical juncture in the field as poor long‐term safety of other MXene compositions challenge the eventual clinical translatability of these materials. Using rational design and synthesis strategies, the Ta4C3Tx MQDs leverage the intrinsic anti‐inflammatory and antiapoptotic properties of tantalum to provide a novel nanoplatform for biomedical engineering. In particular, these MQDs are synthesized with high efficiency and purity using a facile hydrofluoric acid‐free protocol and are enriched with different bioactive functional groups and stable surface TaO2 and Ta2O5. Furthermore, MQDs are spontaneously uptaken into antigen‐presenting endothelial cells and alter surface receptor expression to reduce their activation of allogeneic T‐lymphocytes. Finally, when applied in vivo, Ta4C3Tx MQDs ameliorate the cellular and structural changes of early allograft vasculopathy. These findings highlight the robust potential of tailored Ta4C3Tx MQDs for future applications in medicine. [ABSTRACT FROM AUTHOR]

On behalf of the Organizing Committee of the 6th Annual Meeting of the International Academy of Cardiovascular Sciences North American Section, held in Havana, Cuba, on 5-8 June 2018, we [...]

The application of nontoxic 2D transition‐metal carbides (MXenes) has recently gained ground in bioelectronics. In group‐4 transition metals, tantalum possesses enhanced biological and physical properties compared to other MXene counterparts. However, the application of tantalum carbide for bioelectrodes has not yet been explored. Here, fluorine‐free exfoliation and functionalization of tantalum carbide MAX‐phase to synthesize a novel Ta4C3Tx MXene‐tantalum oxide (TTO) hybrid structure through an innovative, facile, and inexpensive protocol is demonstrated. Additionally, the application of TTO composite as an efficient biocompatible material for supercapacitor electrodes is reported. The TTO electrode displays long‐term stability over 10 000 cycles with capacitance retention of over 90% and volumetric capacitance of 447 F cm−3 (194 F g−1) at 1 mV s−1. Furthermore, TTO shows excellent biocompatibility with human‐induced pluripotent stem cells‐derived cardiomyocytes, neural progenitor cells, fibroblasts, and mesenchymal stem cells. More importantly, the electrochemical data show that TTO outperforms most of the previously reported biomaterials‐based supercapacitors in terms of gravimetric/volumetric energy and power densities. Therefore, TTO hybrid structure may open a gateway as a bioelectrode material with high energy‐storage performance for size‐sensitive applications. [ABSTRACT FROM AUTHOR]

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have demonstrated potential in treating diabetic cardiomyopathy. However, patients with diabetes are on multiple drugs and there is a lack of understanding of how transplanted stem cells would respond in presence of such drugs. Metformin is an AMP kinase (AMPK) activator, the widest used antidiabetic drug. In this study, we investigated the effect of metformin on the efficacy of stem cell therapy in a diabetic cardiomyopathy animal model using streptozotocin (STZ) in male Wistar rats. To comprehend the effect of metformin on the efficacy of BM-MSCs, we transplanted BM-MSCs (1 million cells/rat) with or without metformin. Our data demonstrate that transplantation of BM-MSCs prevented cardiac fibrosis and promoted angiogenesis in diabetic hearts. However, metformin supplementation downregulated BM-MSCmediated cardioprotection. Interestingly, both BM-MSCs and metformin treatment individually improved cardiac function with no synergistic effect of metformin supplementation along with BM-MSCs. Investigating the mechanisms of loss of efficacy of BMMSCs in the presence of metformin, we found that metformin treatment impairs homing of implanted BM-MSCs in the heart and leads to poor survival of transplanted cells. Furthermore, our data demonstrate that metformin-mediated activation of AMPK is responsible for poor homing and survival of BM-MSCs in the diabetic heart. Hence, the current study confirms that a conflict arises between metformin and BM-MSCs for treating diabetic cardiomyopathy. Approximately 10% of the world population is diabetic to which metformin is prescribed very commonly. Hence, future cell replacement therapies in combination with AMPK inhibitors may be more effective for patients with diabetes. [ABSTRACT FROM AUTHOR]