Research progress of megakaryocytes and platelets in lung injury.

The lung is an important site of extramedullary platelet formation, and megakaryocytes in the lung participate in immune responses in addition to platelet production. In acute lung injury and chronic lung injury, megakaryocytes and platelets play a promoting or protective role through different mechanisms. The authors reviewed the role of megakaryocytes and platelets in common clinical lung injuries with different course of disease and different pathogenic factors in order to provide new thinking for the diagnosis and treatment of lung injuries.

What is the context?Platelets are specialized non-nucleated blood cells produced by cytoplasmic lysis of megakaryocytes.HSCs differentiate into granular mature megakaryocytes and produce platelets.Lung is a reservoir of megakaryocytes and a site where platelets are produced in addition to bone marrow and spleen.Lung injury can be divided into acute lung injury and chronic lung injury, and characterized by different pathogenesis.Platelets and megakaryocytes are involved in hemostasis and regulation of the body 's inflammatory response.The disease state of the lung affects the functions of megakaryocytes and platelets.The role of megakaryocytes and platelets in acute and chronic lung injury is poorly studied.What is new?Platelets in the lung are derived not only from the spleen and bone marrow, but also from megakaryocytes in the pulmonary circulation. In this study, we demonstrated that pulmonary megakaryocytes not only produce platelets to play a hemostatic role in lung injury, but also participate in inflammation and immune response with platelets to promote the process of lung injury or play a protective role.Therefore, it was suggested in our analysis that targeting lung megakaryocytes and platelets is currently a new direction for the treatment of a variety of lung injuries.What is the impact?This review intends to explain the relationship between megakaryocytes, platelets and many types of lung injury from the mechanism of platelet production in the lung, and make a prospect in the new progress in the diagnosis and treatment of lung injury.

UBDP1 pseudogene and UBD network competitively bind miR­6072 to promote glioma progression.

Increasing evidence suggests that pseudogenes play crucial roles in various cancers, yet their functions and regulatory mechanisms in glioma pathogenesis remain enigmatic. In the present study, a novel pseudogene was identified, UBDP1, which is significantly upregulated in glioblastoma and positively correlated with the expression of its parent gene, UBD. Additionally, high levels of these paired genes are linked with a poor prognosis for patients. In the present study, clinical samples were collected followed by various analyses including microarray for long non­coding RNAs, reverse transcription­quantitative PCR, fluorescence in situ hybridization and western blotting. Cell lines were authenticated and cultured then subjected to various assays for proliferation, migration, and invasion to investigate the molecular mechanisms. Bioinformatic tools identified miRNA targets, and luciferase reporter assays validated these interactions. A tumor xenograft model in mice was used for in vivo studies. In vitro and in vivo studies have demonstrated that UBDP1, localized in the cytoplasm, functions as a tumor­promoting factor influencing cell proliferation, migration, invasion and tumor growth. Mechanistic investigations have indicated that UBDP1 exerts its oncogenic effects by decoying miR­6072 from UBD mRNA, thus forming a competitive endogenous RNA network, which results in the enhanced oncogenic activity of UBD. The present findings offered new insights into the role of pseudogenes in glioma progression, suggesting that targeting the UBDP1/miR­6072/UBD network may serve as a potential therapeutic strategy for glioma patients.

Developing a novel necroptosis-related signature to evaluate the prognostic and therapeutic characteristics of esophageal cancer.

BACKGROUND: The prognostic assessment and therapeutic interventions of esophageal cancer (ESCA) require novel molecular targets. The prognostic value of necroptosis, a specific mode of programmed cell death strongly linked to cancer progression, remains largely unexplored in ESCA. The primary goal of this research is to develop a necroptosis-based prognostic signature, which will represent the microenvironmental characteristics and prognosis of individuals diagnosed with ESCA. METHODS: Transcriptome data of ESCA samples from The Cancer Genome Atlas were utilized to screen for necroptosis-related long non-coding RNAs (NR-lncRNAs) and genes (NRGs). The research employed the least absolute shrinkage and selection operator (LASSO) regression and univariate Cox regression analysis to identify prognostic candidates. Based on these analyses, a signature was developed in the training set and subsequently verified in the testing and entire sets. A clinicopathologic relevance assessment was carried out, after which a nomogram was established. The features of the immune microenvironment, functional pathways, mutational burden, checkpoint expression, and stemness of tumors were analyzed. Moreover, the sensitivity of individuals to immunotherapy and chemotherapy was compared for therapeutic guidance. RESULTS: A necroptosis-associated signature comprising two genes and eleven lncRNAs was constructed. High-risk patients showed worse prognosis and clinicopathologic features, with more tumor-infiltrating naïve B cells, CD4+ memory resting T cells, and regulatory T cells. Furthermore, stromal and ESTIMATE scores were decreased along with increased stemness scores and tumor mutational burden in high-risk individuals. For the quantitative prediction of the outcomes of individuals, a nomogram was established. High-risk individuals showed greater sensitivity to immunotherapy while low-risk individuals benefited more from conventional chemotherapeutic or targeted therapy. CONCLUSION: A necroptosis-related prognostic signature was developed to study the tumor microenvironment, mutational burden, clinical features, and the treatment response of ESCA patients. This may contribute to precision medicine for ESCA.

Glioma­neuronal interactions in tumor progression: Mechanism, therapeutic strategies and perspectives (Review).

An increasing body of evidence has become available to reveal the synaptic and functional integration of glioma into the brain network, facilitating tumor progression. The novel discovery of glioma­neuronal interactions has fundamentally challenged our understanding of this refractory disease. The present review aimed to provide an overview of how the neuronal activities function through synapses, neurotransmitters, ion channels, gap junctions, tumor microtubes and neuronal molecules to establish communications with glioma, as well as a simplified explanation of the reciprocal effects of crosstalk on neuronal pathophysiology. In addition, the current state of therapeutic avenues targeting critical factors involved in glioma­euronal interactions is discussed and an overview of clinical trial data for further investigation is provided. Finally, newly emerging technologies, including immunomodulation, a neural stem cell­based delivery system, optogenetics techniques and co­culture of neuron organoids and glioma, are proposed, which may pave a way towards gaining deeper insight into both the mechanisms associated with neuron­ and glioma­communicating networks and the development of therapeutic strategies to target this currently lethal brain tumor.

[Placental mechanisms underlying the effects of maternal stress on the fetal development].

Placenta is the only link between the pregnant woman and fetus, and the basis for maintaining the normal pregnancy process and fetal development. Maternal stress is the maternal physiological and psychological changes caused by various factors, characterized by the increased level of glucocorticoid, which affects the hypothalamic-pituitary-target gland axis and regulates the expression of target genes. Maternal stress also changes the weight, metabolism and nutrient transportation of the placenta, which will substantially influence the development of fetus. This paper will firstly summarize the characteristics of maternal stress and its influence on offspring. Then, the changes in the body under maternal stress will be described. Finally, we will clarify the proven mechanisms underlying maternal stress and raise some important problems that have not been clarified in this area. The study of maternal stress on fetus and its underlying mechanisms will serve as theoretical basis for the diagnosis and treatment of the stress-related pregnant diseases and disorders.

Applications of Mesenchymal Stem Cells in Liver Fibrosis: Novel Strategies, Mechanisms, and Clinical Practice.

Liver fibrosis is a common result of most chronic liver diseases, and advanced fibrosis often leads to cirrhosis. Currently, there is no effective treatment for liver cirrhosis except liver transplantation. Therefore, it is important to carry out antifibrosis treatment to reverse liver damage in the early stage of liver fibrosis. Mesenchymal stem cells (MSCs) are the most widely used stem cells in the field of regenerative medicine. The preclinical and clinical research results of MSCs in the treatment of liver fibrosis and cirrhosis show that MSC administration is a promising treatment for liver fibrosis and cirrhosis. MSCs reverse liver fibrosis and increase liver function mainly through differentiation into hepatocytes, immune regulation, secretion of cytokines and other nutritional factors, reduction of hepatocyte apoptosis, and promotion of hepatocyte regeneration. Recently, many studies provided a variety of new methods and strategies to improve the effect of MSCs in the treatment of liver fibrosis. In this review, we summarized the current effective methods and strategies and their potential mechanisms of MSCs in the treatment of liver fibrosis, as well as the current research progress in clinical practice. We expect to achieve complete reversal of liver injury with MSC-based therapy in the future.