The role of stromal cells in epithelial-mesenchymal plasticity and its therapeutic potential.

The epithelial-mesenchymal transition (EMT) is a critical tumor invasion and metastasis process. EMT enables tumor cells to migrate, detach from their original location, enter the circulation, circulate within it, and eventually exit from blood arteries to colonize in foreign sites, leading to the development of overt metastases, ultimately resulting in death. EMT is intimately tied to stromal cells around the tumor and is controlled by a range of cytokines secreted by stromal cells. This review summarizes recent research on stromal cell-mediated EMT in tumor invasion and metastasis. We also discuss the effects of various stromal cells on EMT induction and focus on the molecular mechanisms by which several significant stromal cells convert from foes to friends of cancer cells to fuel EMT processes via their secretions in the tumor microenvironment (TME). As a result, a better knowledge of the role of stromal cells in cancer cells' EMT may pave the path to cancer eradication.

Protective Effect of Hydrogen Sulfide on Cerebral Ischemia-Reperfusion Injury.

The brain is the most sensitive organ to hypoxia in the human body. Hypoxia in the brain will lead to damage to local brain tissue. When the blood supply of ischemic brain tissue is restored, the damage will worsen, that is, cerebral ischemia-reperfusion injury. Hydrogen sulfide (H2S) is a gaseous signal molecule and a novel endogenous neuroregulator. Indeed, different concentrations of H2S have different effects on neurons. Low concentration of H2S can play an important protective role in cerebral ischemia-reperfusion injury by inducing anti-oxidative stress injury, inhibition of inflammatory response, inhibition of cell apoptosis, reduction of cerebrovascular endothelial cell injury, regulation of autophagy, and other ways, which provides a new idea for clinical diagnosis and treatment of related diseases. This review aims to report the recent research progress on the dual effect of H2S on brain tissue during cerebral ischemia/reperfusion injury.

Atractylenolide II induces cell cycle arrest and apoptosis in breast cancer cells through ER pathway.

In this research, atractylenolide II (ATR II) on apoptosis, cell cycle cells via ER pathway in breast cancer (MDA-MB-231 and MCF-7) cells are assessed. The effect of ATR II on cell proliferation was detected by MTT assay. Additional flow cytometry, luciferase, the western blot were performed to detect the signaling pathway cytotoxicity of ATR II. We have also carried out autodock measurements to validate our results. Our findings showed ATR II could inhibit breast cancer cell growth by apoptosis mainly through G2/M-phase cell cycle arrest. Besides, the cytotoxicity of ATTR II on breast cancer was also correlated by the regulation of endrogen receptors and promising an anti-inflammatory activity via inhibiting NF-KB signaling pathways. Taking together, ATR II could be a potential anti-cancer drug for breast cancer.

Mesenchymal stem cell-derived exosome microRNA as therapy for cardiac ischemic injury.

Cardiovascular diseases (CVD) are a significant cause of human health harm. In the past, stem cell therapy was reported to have functional defects, such as immune rejection, tumorigenicity, and infusion toxicity. Exosomes are extracellular vesicles with lipid bilayer membrane structure, containing proteins, lipids, mRNA, miRNA, DNA, and other molecules, which can mediate various biological functions such as immune response, inflammatory response, cell migration, and differentiation intercellular communication. Exosomal miRNAs have outstanding advantages in disease diagnosis and curative effect prediction. Likewise, paracrine factors could also mediate the main therapeutic effect of mesenchymal stem cells. Research has shown that mesenchymal stem cell-derived micro-exosomes, which may come from stem cells, accumulate in the ischemic tissue and regulate cell proliferation, apoptosis, inflammation, and angiogenesis sites of myocardial injury after being transplanted. This review reviewed the molecular mechanisms of exosomes and internal microRNAs derived from mesenchymal stem cells in cardiac ischemic injury repair.

Application of mesenchymal stem cell-derived exosomes in kidney diseases.

Kidney injury (KI) has high morbidity and mortality; there has been no ideal practical treatment available in clinical practice until now. Exosomes are formed from fusing multisubunit body membranes and are secreted into the extracellular matrix, intercellular communication membracusses. As a cell-free treatment, it offers a new approach to the treatment of KI. Exosomes are spherical vesicles with or no separator cup that shapes proteins, and RNA acts on the target cells through various means to promote tissue damage and mitigate apoptosis, both inflammation and oxidative stress. Exosomes derived from mesenchymal stem cells (MSC) have a paracrine function in promoting tissue repair and immune regulation. The MSC-Exos provide specific benefits over the MSCs. The urinary exosomes closely follow the functions and diseases of the kidneys. Though much of the research in this field is only at the preliminary stages, previous research has demonstrated that MSC-Exos damaged tissues to offer proteins, mRNAs, and microRNAs as remedies for kidney injury. Although exosomes' role in tissue repair is currently is greatly debated, several key issues remain unaddressed. This is a summarization of the work done concerning MSC in the treatment of KI.

Potential effects of SARS-CoV-2 on the gastrointestinal tract and liver.

COVID-19 is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early reported symptoms include fever, cough, and respiratory symptoms. There were few reports of digestive symptoms. However, with COVID-19 spreading worldwide, symptoms such as vomiting, diarrhoea, and abdominal pain have gained increasing attention. Research has found that angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor, is strongly expressed in the gastrointestinal tract and liver. Whether theoretically or clinically, many studies have suggested a close connection between COVID-19 and the digestive system. In this review, we summarize the digestive symptoms reported in existing research, discuss the impact of SARS-CoV-2 on the gastrointestinal tract and liver, and determine the possible mechanisms and aetiology, such as cytokine storm. In-depth exploration of the relationship between COVID-19 and the digestive system is urgently needed.

A Comprehensive Review of the Therapeutic Value of Urine-Derived Stem Cells.

Stem cells possess regenerative powers and multidirectional differentiation potential and play an important role in disease treatment and basic medical research. Urine-derived stem cells (USCs) represent a newly discovered type of stem cell with biological characteristics similar to those of mesenchymal stromal cells (MSCs), including their doubling time and immunophenotype. USCs are noninvasive and can be readily obtained from voided urine and steadily cultured. Based on advances in this field, USCs and their secretions have increasingly emerged as ideal sources. USCs may play regulatory roles in the cellular immune system, oxidative stress, revascularization, apoptosis and autophagy. This review summarizes the applications of USCs in tissue regeneration and various disease treatments. Furthermore, by analysing their limitations, we anticipate the development of more feasible therapeutic strategies to promote USC-based individualized treatment.

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.

Global transcriptome study of Dip2B-deficient mouse embryonic lung fibroblast reveals its important roles in cell proliferation and development.

Disco-interacting protein 2 homolog B (Dip2B) is a member of Dip2 family encoded by Dip2b gene. Dip2B has been reported to regulate murine epithelial KIT+ progenitor cell expansion and differentiation epigenetically via exosomal miRNA targeting during salivary gland organogenesis. However, its molecular functions, cellular activities and biological process remain unstudied. Here, we investigated the transcriptome of Dip2B-deficient mouse embryonic lung fibroblasts (MELFs) isolated from E14.5 embryos by RNA-Seq. Expression profiling identified 1369 and 1104 differentially expressed genes (DEGs) from Dip2b-/- and Dip2b+/- MELFs in comparisons to wild-type (Dip2b+/+ ). Functional clustering of DEGs revealed that many gene ontology terms belong to membrane activities such as 'integral component of plasma membrane', and 'ion channel activity', suggesting possible roles of Dip2B in membrane integrity and membrane function. KEGG pathway analysis revealed that multiple metabolic pathways are affected in Dip2b- / - and Dip2b +/ - when compared to Dip2b +/+ MELFs. These include 'protein digestion and absorption', 'pancreatic secretion' and 'steroid hormone synthesis pathway'. These results suggest that Dip2B may play important roles in metabolism. Molecular function analysis shows transcription factors including Hox-genes, bHLH-genes, and Forkhead-genes are significantly down-regulated in Dip2b- / - MELFs. These genes are critical in embryo development and cell differentiation. In addition, Dip2B-deficient MELFs demonstrated a reduction in cell proliferation and migration, and an increase in apoptosis. All results indicate that Dip2B plays multiple roles in cell proliferation, migration and apoptosis during embryogenesis and may participate in control of metabolism. This study provides valuable information for further understanding of the function and regulatory mechanisms of Dip2B.

Implication of Gut Microbiota in Cardiovascular Diseases.

Emerging evidence has identified the association between gut microbiota and various diseases, including cardiovascular diseases (CVDs). Altered intestinal flora composition has been described in detail in CVDs, such as hypertension, atherosclerosis, myocardial infarction, heart failure, and arrhythmia. In contrast, the importance of fermentation metabolites, such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and secondary bile acid (BA), has also been implicated in CVD development, prevention, treatment, and prognosis. The potential mechanisms are conventionally thought to involve immune regulation, host energy metabolism, and oxidative stress. However, numerous types of programmed cell death, including apoptosis, autophagy, pyroptosis, ferroptosis, and clockophagy, also serve as a key link in microbiome-host cross talk. In this review, we introduced and summarized the results from recent studies dealing with the relationship between gut microbiota and cardiac disorders, highlighting the role of programmed cell death. We hope to shed light on microbiota-targeted therapeutic strategies in CVD management.

Current situation and future of stem cells in cardiovascular medicine.

Cardiovascular disease (CVD) is one of the leading causes of death worldwide. Currently, many methods have been proposed by researchers for the prevention and treatment of CVD; among them, stem cell-based therapies are the most promising. As the cells of origin for various mature cells, stem cells have the ability to self-renew and differentiate. Stem cells have a powerful ability to regenerate biologically, self-repair, and enhance damaged functional tissues or organs. Allogeneic stem cells and somatic stem cells are two types of cells that can be used for cardiac repair. Theoretically, dilated cardiomyopathy and acute myocardial infarction can be treated with such cells. In addition, stem cell transplantation procedures, including intravenous, epicardial, cardiac, and endocardial injections, have been reported to provide significant benefits in clinical practice; however, there are still a number of issues that need further study and consideration, such as the form and quantity of transplanted cells and post-transplantation health. The goal of this analysis was to summarize the recent advances in stem cell-based therapies and their efficacy in cardiovascular regenerative medicine.

Oxygen homeostasis and cardiovascular disease: A role for HIF?

Hypoxia, the decline of tissue oxygen stress, plays a role in mediating cellular processes. Cardiovascular disease, relatively widespread with increased mortality, is closely correlated with oxygen homeostasis regulation. Besides, hypoxia-inducible factor-1(HIF-1) is reported to be a crucial component in regulating systemic hypoxia-induced physiological and pathological modifications like oxidative stress, damage, angiogenesis, vascular remodeling, inflammatory reaction, and metabolic remodeling. In addition, HIF1 controls the movement, proliferation, apoptosis, differentiation and activity of numerous core cells, such as cardiomyocytes, endothelial cells (ECs), smooth muscle cells (SMCs), and macrophages. Here we review the molecular regulation of HIF-1 in cardiovascular diseases, intended to improve therapeutic approaches for clinical diagnoses. Better knowledge of the oxygen balance control and the signal mechanisms involved is important to advance the development of hypoxia-related diseases.

Urine-Derived Induced Pluripotent Stem Cells in Cardiovascular Disease.

Recent studies have demonstrated that stem cells are equipped with the potential to differentiate into various types of cells, including cardiomyocytes. Meanwhile, stem cells are highly promising in curing cardiovascular diseases. However, owing to the ethical challenges posed in stem cell acquisition and the complexity and invasive nature of the method, large-scale expansions and clinical applications in the laboratory have been limited. The current generation of cardiomyocytes is available from diverse sources; urine is one of the promising sources among them. Although advanced research was established in the generation of human urine cells as cardiomyocytes, the reprogramming of urine cells to cardiomyocytes remains unclear. In this context, it is necessary to develop a minimally invasive method to create induced pluripotent stem cells (iPSCs). This review focuses on the latest advances in research on urine-derived iPSCs and their application mechanisms in cardiovascular diseases.

A Comprehensive Review on Schisandrin B and Its Biological Properties.

Nature is a vast source of bioactive molecules and has provided an active and efficient reservoir for drug discovery. Among natural compounds, one of the most promising is Schisandrin B (Sch B), isolated from Schisandra chinensis, which was documented to possess diversified pharmacokinetic propriety, among them antioxidant, anti-inflammation, cardioprotection, and neuroprotection. Due to its large biological properties, Sch B was recorded to be a potent cure for several diseases by targeting several signaling pathways. This review is aimed at emphasizing the recent data on the biological properties of Sch B among the molecular mechanism of this drug on tumoral, cardiac, and neural diseases. The data suggest that the antitumor activities of Sch B were mainly through apoptosis and cell cycle arrest at the diver's stage. It is reported that Sch B could be used as effective chemotherapy, neuroprotection, and cardioprotection since it possesses a spectrum of biological activities; however, further investigations on the mechanism of its action and preclinical trials are still mandatory to further validate the potential of this natural drug candidate.

Macrophages: First guards in the prevention of cardiovascular diseases.

Cardiovascular diseases (CVD) remain one of the leading causes of mortality worldwide, especially in developing countries. It is widely known that severe inflammation can lead to atherosclerosis, which can cause various downstream pathologies, including myocardial injury and viral myocarditis. To date, several strategies have been proposed to prevent and cure CVD. The use of targeting macrophages has emerged as one of the most effective therapeutic approaches. Macrophages play a crucial role in eliminating senescent and dead cells while maintaining myocardial electrical activity and repairing myocardial injury. They also contribute to tissue repair and remodeling and plaque stabilization. Targeting macrophage pathways can, therefore, be advantageous in CVD care since it can lead to decreased aggregation of mononuclear cells at the injured site in the heart. Furthermore, it inhibits the development of pro-inflammatory factors, facilitates cholesterol outflow, and reduces the lipid concentration. More in-depth studies are still needed to formulate a comprehensive classification of phenotypes for different macrophages and determine their roles in the pathogenesis of CVD. In this review, we summarize the recent advances in the understanding of the role of macrophages in the prevention and cure of CVD.

Efficiency of Traditional Chinese medicine targeting the Nrf2/HO-1 signaling pathway.

Cardiovascular disease (CVD) is a significant cause of death worldwide. Because of its major individual differences in genetic background, pathogenesis, and disease progression pattern, the mortality risk rate remains high following conventional Western medicine diagnosis under current guidelines. Traditional Chinese medicine (TCM) has important multi-target, multi-pathway, and multi-layer benefits that can effectively address western medicine deficiencies. It was therefore commonly used in CVD diagnosis. Oxidative stress is also one of the main factors of CVD. Likewise, this main reaction regulator is the nuclear factor erythroid-2-related (Nrf2) factor. When activated, it can be transferred to the nucleus and initiated in the downstream pathway, thus playing an anti-oxidant stress role. As one of the most crucial endogenous protection systems in the body, Nrf2-related / heme oxygenase 1 (Nrf2/HO-1) signaling pathway is Nrf2's most classic approach to playing roles. Recently, various advances have been made to research and explain TCM by manipulating this pathway to treat CVD using modern molecular biology and other approaches. This analysis summarized the relationship between Nrf2/HO-1 signaling route, CVD and TCM. Further, Autodock calculation was also conducted to determine the binding amino acid on this TCM to Nrf2 and HO-1.

Effects of imperatorin in the cardiovascular system and cancer.

Patients with cancer survivors are at increased risk of cardiovascular disease(CVD). Cardio-oncology has developed as a new discipline with the advances in cancer treatment. There are many new challenges for the clinician and a new frontier for research and investigation. There is an urgent need for further study on the prevention of cardiovascular toxicity. Imperatorin (IMP) is a natural form of coumarin and extract from several plants with diver's pharmacokinetic effects, including antioxidant and anti-inflammatory properties. This review focus on the molecular mechanisms and pharmacological effects of Imperatorin maybe provide potential cancer and cardiovascular protection that targets IMP. Further studies are required to elucidate the entire spectrum of cytotoxic activities of these compounds to validate and expand their preclinical and clinical applications and to clarify the potential role of IMP.