Stem Cell Therapies for Restorative Treatments of Central Nervous System Ischemia-Reperfusion Injury.

Ischemic damage to the central nervous system (CNS) is a catastrophic postoperative complication of aortic occlusion subsequent to cardiovascular surgery that can cause brain impairment and sometimes even paraplegia. Over recent years, numerous studies have investigated techniques for protecting and revascularizing the nervous system during intraoperative ischemia; however, owing to a lack of knowledge of the physiological distinctions between the brain and spinal cord, as well as the limited availability of testing techniques and treatments for ischemia-reperfusion injury, the cause of brain and spinal cord ischemia-reperfusion injury remains poorly understood, and no adequate response steps are currently available in the clinic. Given the limited ability of the CNS to repair itself, it is of great clinical value to make full use of the proliferative and differentiation potential of stem cells to repair nerves in degenerated and necrotic regions by stem cell transplantation or mobilization, thereby introducing a novel concept for the treatment of severe CNS ischemia-reperfusion injury. This review summarizes the most recent advances in stem cell therapy for ischemia-reperfusion injury in the brain and spinal cord, aiming to advance basic research and the clinical use of stem cell therapy as a promising treatment for this condition.

Maturation of induced pluripotent stem cell-derived cardiomyocytes and its therapeutic effect on myocardial infarction in mouse.

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have an irreplaceable role in the treatment of myocardial infarction (MI), which can be injected into the transplanted area with new cardiomyocytes (Cardiomyocytes, CMs), and improve myocardial function. However, the immaturity of the structure and function of iPSC-CMs is the main bottleneck at present. Since collagen participates in the formation of extracellular matrix (ECM), we synthesized nano colloidal gelatin (Gel) with collagen as the main component, and confirmed that the biomaterial has good biocompatibility and is suitable for cellular in vitro growth. Subsequently, we combined the PI3K/AKT/mTOR pathway inhibitor BEZ-235 with Gel and found that the two combined increased the sarcomere length and action potential amplitude (APA) of iPSC-CMs, and improved the Ca2+ processing ability, the maturation of mitochondrial morphological structure and metabolic function. Not only that, Gel can also prolong the retention rate of iPSC-CMs in the myocardium and increase the expression of Cx43 and angiogenesis in the transplanted area of mature iPSC-CMs, which also provides a reliable basis for the subsequent treatment of mature iPSC-CMs.

Immunomodulatory effects of icariin in a myocardial infarction mouse model.

Myocardial infarction (MI) is a prevalent cardiovascular disease defined by myocardial ischemia and hypoxic damage caused by plaque rupture, thrombosis, lumen stenosis, or blockage in the coronary artery. However, the development of emergency percutaneous coronary interventional therapy has enabled the rapid restoration of blood perfusion to ischemic myocardium and the rescue of dying myocardium cells. Some dying myocardium cells have caused irreversible damage and impaired cardiac function recovery in recent years. Icariin has been utilized to treat various ailments as a natural chemical extract. In this study, we employed a variety of approaches to observe MI, including western blotting, quantitative RT-PCR, immunohistochemistry, and flow cytometric analysis using icariin. As demonstrated by the research findings, icariin may prevent MI-induced cell apoptosis. This is accomplished by inhibiting proinflammatory factors via the Nrf2/HO-1 signaling pathways. These data imply that icariin may be an effective treatment for MI.

A Deep Insight Into Regulatory T Cell Metabolism in Renal Disease: Facts and Perspectives.

Kidney disease encompasses a complex set of diseases that can aggravate or start systemic pathophysiological processes through their complex metabolic mechanisms and effects on body homoeostasis. The prevalence of kidney disease has increased dramatically over the last two decades. CD4+CD25+ regulatory T (Treg) cells that express the transcription factor forkhead box protein 3 (Foxp3) are critical for maintaining immune homeostasis and preventing autoimmune disease and tissue damage caused by excessive or unnecessary immune activation, including autoimmune kidney diseases. Recent studies have highlighted the critical role of metabolic reprogramming in controlling the plasticity, stability, and function of Treg cells. They are also likely to play a vital role in limiting kidney transplant rejection and potentially promoting transplant tolerance. Metabolic pathways, such as mitochondrial function, glycolysis, lipid synthesis, glutaminolysis, and mammalian target of rapamycin (mTOR) activation, are involved in the development of renal diseases by modulating the function and proliferation of Treg cells. Targeting metabolic pathways to alter Treg cells can offer a promising method for renal disease therapy. In this review, we provide a new perspective on the role of Treg cell metabolism in renal diseases by presenting the renal microenvironment、relevant metabolites of Treg cell metabolism, and the role of Treg cell metabolism in various kidney diseases.

Histatin-1 loaded multifunctional, adhesive and conductive biomolecular hydrogel to treat diabetic wound.

Micro-/macroangiopathy, neuropathy and prolonged inflammation are common in diabetic wound, however, traditional wound dressing cannot treat these problems in the same time. Herein, we developed a multifunctional hydrogel with promoted angiogenesis, cell proliferation and anti-inflammation ability to treat diabetic wound. The hydrogel was composed of natural polymers, including gelatin and chitosan, which have excellent biocompatibility. Histatin-1 (His-1) was added into the hydrogel to improve the cell adhesion, proliferation and angiogenesis. Besides, polypyrrole based conductive nanoparticles (G-Ppy) were introduced in the hydrogel to enhance the electrical signal conduction between skin and promote the mechanical strength of the hydrogel. The polypyrrole nanoparticles were growth in the chain of methacryloyl grafted gelatin (Gel-MA), leading to a better biocompatibility and water dispersibility. In vivo wound healing experiment proved that the hydrogel accelerated the wound healing rate, down regulation the expression of pro-inflammation factor TNF-α and upregulation the expression of CD31 and α-SMA, indicating the prospects in the application of diabetic wound healing.

Spatial heterogeneity of soil heavy metal content in Baiyinhua mining area, Inner Mongolia, China.

To evaluate the spatial distribution characteristics of soil heavy metal content in Xiwuzhumuqin Banner, Inner Mongolia, we analyzed the spatial heterogeneity of soil Cu, Cr, Pb, and Mn contents within 8 km distance of the mining area. Results showed that the contents of Cu, Cr, Pb and Mn in soil were 12.7, 32.6, 29.9 and 201.3 mg·kg-1, and their coefficients of variation were 26.8%, 33.9%, 27.1% and 45.7%, respectively. According to the model fitting by semi-variance function, the spatial distribution of Cu, Cr, Pb and Mn were consistent with the Gaussian model, Gaussian model, Gaussian model and linear model, respectively. Results of the spatial distribution pattern analysis showed that the spatial correlation levels of Mn, Cr and Cu were high, which were mainly affected by structural factors, but little affected by random factors. The spatial correlation level of Pb element was moderate, which was affected by both structural factors and random factors. Results of the fractal dimension analysis showed that the spatial distribution of four heavy metal contents was simple. Combined with 2D and 3D views, the four types of heavy metals all presented gradient distribution, which decreased with the increases of distance. The contents of Cu and Mn were mainly concentrated within 1.5 km from the mining area, while Cr and Pb were mainly concentrated within 2.0 km and 3.0 km from the mining area, respectively.

Maturation strategies and limitations of induced pluripotent stem cell-derived cardiomyocytes.

Induced pluripotent stem cells (iPSCs) have the ability to differentiate into cardiomyocytes (CMs). They are not only widely used in cardiac pharmacology screening, human heart disease modeling, and cell transplantation-based treatments, but also the most promising source of CMs for experimental and clinical applications. However, their use is largely restricted by the immature phenotype of structure and function, which is similar to embryonic or fetal CMs and has certain differences from adult CMs. In order to overcome this critical issue, many studies have explored and revealed new strategies to induce the maturity of iPSC-CMs. Therefore, this article aims to review recent induction methods of mature iPSC-CMs, related mechanisms, and limitations.

Immunomodulatory Effects of Heme Oxygenase-1 in Kidney Disease.

Kidney disease is a general term for heterogeneous damage that affects the function and the structure of the kidneys. The rising incidence of kidney diseases represents a considerable burden on the healthcare system, so the development of new drugs and the identification of novel therapeutic targets are urgently needed. The pathophysiology of kidney diseases is complex and involves multiple processes, including inflammation, autophagy, cell-cycle progression, and oxidative stress. Heme oxygenase-1 (HO-1), an enzyme involved in the process of heme degradation, has attracted widespread attention in recent years due to its cytoprotective properties. As an enzyme with known anti-oxidative functions, HO-1 plays an indispensable role in the regulation of oxidative stress and is involved in the pathogenesis of several kidney diseases. Moreover, current studies have revealed that HO-1 can affect cell proliferation, cell maturation, and other metabolic processes, thereby altering the function of immune cells. Many strategies, such as the administration of HO-1-overexpressing macrophages, use of phytochemicals, and carbon monoxide-based therapies, have been developed to target HO-1 in a variety of nephropathological animal models, indicating that HO-1 is a promising protein for the treatment of kidney diseases. Here, we briefly review the effects of HO-1 induction on specific immune cell populations with the aim of exploring the potential therapeutic roles of HO-1 and designing HO-1-based therapeutic strategies for the treatment of kidney diseases.

Establishment of a CRISPR/Cas9-mediated GATAD2B homozygous knockout human embryonic stem cell line.

As a subunit of the nucleosome remodeling and histone deacetylation (NuRD) complex, GATA zinc finger domain containing 2B (GATAD2B) plays a vital role in chromatin modification and transcriptional regulation. To further investigate the role of GATAD2B in cell fate determination of human ESCs, we generated two GATAD2B homozygous knockout human ESC lines by CRISPR/Cas9 technology. The cell line exhibits normal karyotype and typical stem cell morphology, following the high expression of pluripotent genes and differentiation potential in vitro. These cell lines will provide cell resources to investigate epigenetic regulation in extensive biological processes as menthioned above.

[Composition and spatial distribution of main species in grassland community of Baiyinhua mining area, China]. / 白音华矿区草地群落主要物种组成及空间分布.

We analyzed composition and spatial distribution of main species in the surrounding grassland of Baiyinhua mining area in Inner Mongolia. The results showed that there were 55 plant species in the grassland, with dominant species being Stipa grandis, Carex korshinskyi, and Cleistogenes squarrosa, and common species being Leymus chinensis, Agropyron cristatum, and Anemarrhena asphodeloides. The accumulative relative importance value of those six species was 79.6%, with their densities being 26.6, 204.7, 105.4, 107.1, 68.2 and 55.1 individuals·m-2, respectively. The population density of those six species was modeled by the semi-variance function. The population distribution was in accordance with the exponential model, exponential model, exponential model, spherical model, linear model and Gaussian model, respectively. Through analyzing the spatial distribution pattern, structure ratios were 59.2%, 97.2%, 89.1%, 94.5%, 62.6% and 72.1%, respectively. The spatial autocorrelation of C. korshinskyi, C. squarrosa and L. chinensis populations was mainly affected by structural factors, whereas S. grandis, A. cristatum and A. asphodeloides were mainly affected by random factors. According to results from the fractal dimension analysis, population distribution patterns of S. grandis, C. korshinskyi, C. squarrosa and A. cristatum were simple, and the spatial dependence was strong. Both L. chinensis and A. asphodeloides showed contrasting patterns with those four species. From 2D and 3D images, S. grandis and A. asphodeloides showed gradient diffusion, while C. korshinskyi, C. squarrosa, L. chinensis and A. cristatum showed patch distribution. The results showed that the spatial distribution of the main species in this grassland community did not correlate with mining.

Mechanisms of perioperative brain damage in children with congenital heart disease.

Congenital heart disease, particularly cyanotic congenital heart disease (CCHD), may lead to a neurodevelopmental delay through central nervous system injury, more unstable central nervous system development, and increased vulnerability of the nervous system. Neurodevelopmental disease is the most serious disorder of childhood, affecting the quality of life of children and their families. Therefore, the monitoring and optimization of nerve damage treatments are important. The factors contributing to neurodevelopmental disease are primarily related to preoperative, intraoperative, postoperative, genetic, and environmental causes, with intraoperative causes being the most influential. Nevertheless, few studies have examined these factors, particularly the influencing factors during early postoperative care. Children with congenital heart disease may experience brain damage during early heart intensive care due to unstable haemodynamics and total body oxygen transfer, particularly early postoperative inflammatory reactions in the brain, blood glucose levels, and other factors that potentially influence long-term neural development. This study analyses the forms of structural and functional brain damage in the early postoperative period, along with the recent evolution of research on its contributing factors.