Hypoxic pulmonary hypertension (HPH) is a complicated vascular disorder characterized by diverse mechanisms that lead to elevated blood pressure in pulmonary circulation. Recent evidence indicates that HPH is not simply a pathological syndrome but is instead a complex lesion of cellular metabolism, inflammation, and proliferation driven by the reprogramming of gene expression patterns. One of the key mechanisms underlying HPH is hypoxia, which drives immune/inflammation to mediate complex vascular homeostasis that collaboratively controls vascular remodeling in the lungs. This is caused by the prolonged infiltration of immune cells and an increase in several pro-inflammatory factors, which ultimately leads to immune dysregulation. Hypoxia has been associated with metabolic reprogramming, immunological dysregulation, and adverse pulmonary vascular remodeling in preclinical studies. Many animal models have been developed to mimic HPH; however, many of them do not accurately represent the human disease state and may not be suitable for testing new therapeutic strategies. The scientific understanding of HPH is rapidly evolving, and recent efforts have focused on understanding the complex interplay among hypoxia, inflammation, and cellular metabolism in the development of this disease. Through continued research and the development of more sophisticated animal models, it is hoped that we will be able to gain a deeper understanding of the underlying mechanisms of HPH and implement more effective therapies for this debilitating disease.

Background: Hypoxia plays a pivotal role in modulating immune responses, especially in neutrophils, which are essential components of the innate immune system. Hypoxia-inducible factor (HIF)-1α, a key transcription factor in hypoxic adaptation, regulates cellular metabolism and inflammatory responses. However, the impact of HIF-1α-dependent glycolysis on the formation of neutrophil extracellular traps (known as NETosis) under hypoxic conditions remains unclear.Methods: We employed two established neutrophil models, neutrophils isolated from human whole blood and DMSO-induced dHL-60 cells, to explore the role of HIF-1α in regulating glycolysis and its influence on NETosis under hypoxic conditions. We utilized western blotting, immunofluorescence staining, ELISA, and flow cytometry to evaluate the expression of key glycolytic enzymes and NETosis markers under hypoxia. Additionally, the effects of inhibiting HIF-1α with LW6 and blocking the glycolytic pathway with Bay-876 were investigated.Results: HIF-1α-dependent glycolysis, through the upregulation of key glycolytic enzymes, significantly enhances NETosis under hypoxic conditions. Pharmacological inhibition of HIF-1α with LW6 and glycolytic blockade with Bay-876 markedly reduced NETosis, underscoring the crucial role of metabolic reprogramming in neutrophil function during hypoxia.Conclusion: This study provides novel insights into the interplay between metabolic reprogramming and NETosis in response to hypoxic stress. We identify HIF-1α-dependent glycolysis as a key driver of NETs formation, advancing our understanding of the mechanisms underlying hypoxia-related inflammatory diseases. These findings also suggest that targeting metabolic pathways may offer potential therapeutic strategies for modulating immune responses in hypoxia-associated disorders.

Kidney disease is a major global health concern, affecting millions of people. Nephrologists have shown interest in platelets because of coagulation disorders caused by renal diseases. With a better understanding of platelets, it has been found that these anucleate and abundant blood cells not only play a role in hemostasis, but also have important functions in inflammation and immunity. Platelets are not only affected by kidney disease, but may also contribute to kidney disease progression by mediating inflammation and immune effects. This review summarizes the current evidence regarding platelet abnormalities in renal disease, and the multiple effects of platelets on kidney disease progression. The relationship between platelets and kidney disease is still being explored, and further research can provide mechanistic insights into the relationship between thrombosis, bleeding, and inflammation related to kidney disease, and elucidate targeted therapies for patients with kidney disease.

Renal diseases, particularly acute kidney injury (AKI) and chronic kidney disease (CKD), are significant global health challenges. These conditions impair kidney function and can lead to serious complications, including cardiovascular diseases, which further exacerbate the public health burden. Currently, the global AKI mortality rate is alarmingly high (20%–50%); CKD is projected to emerge as a major global health burden by 2040. Existing treatments such as hemodialysis and kidney transplantation have limited effectiveness and are often associated with adverse effects. Mesenchymal stem cells (MSCs) offer considerable potential for treating renal diseases owing to their regenerative and immunomodulatory properties. Thus, this review focuses on the application of MSCs in renal disease, discusses fundamental research findings, and evaluates their application in clinical trials. Moreover, we discuss the impact and safety of MSCs as a therapeutic option and highlight challenges and potential directions for their clinical application. We selected research articles from PubMed published within the last 5 years (from 2019), focusing on high‐impact journals and clinical trial data, and included a few key studies predating 2019. Considerations included the novelty of the research, sample size, experimental design, and data reliability. With advancements in single‐cell sequencing, CRISPR/Cas9 gene editing, and other cutting‐edge technologies, future MSC research will explore combination therapies and personalized treatments to provide more promising, safer treatments with reduced adverse reactions and enhanced therapeutic outcomes. These advances will improve kidney disease treatment methods, enhance patient quality of life, and maximize the benefits of MSC therapies.

Milk‐derived exosomes (MDEs), being a component of milk, have the potential to support immune system maturation in offspring and enhance immune cell proliferation. Through the transport and transmission of essential signaling molecules, MDEs contribute to the regulation of intergenerational and intraspecies communication, thereby impacting nutrient uptake and metabolic functions. A comprehensive comprehension of MDE functionalities is imperative for enhancing the quality of the dairy industry. A systematic search of the databases PubMed/Medline, Web of Science, and Scopus utilizing predetermined keywords resulted in the identification of 418 articles, of which 67 were chosen for inclusion in this review, which specifically explores the intersection of immune response and nutrition. This article provides a critical analysis of the classification of extracellular vesicles, the mechanisms underlying the biosynthesis of microvesicular dietary exosomes (MDEs), the components of MDEs, and their relevance in the contexts of nutrition and immune modulation. The primary aim of this review was to offer valuable scholarly insights to support the advancement and practical application of MDEs.

High-altitude polycythemia (HAPC) can occur in individuals who are intolerant to high-altitude hypoxia. In patients with HAPC, erythrocytosis is often accompanied by a decrease in platelet count. Chronic hypoxia can increase the incidence of arteriovenous thrombosis and the risk of bleeding during antithrombotic treatment due to thrombocytopenia; therefore, understanding the cause of thrombocytopenia can reduce the risk of treatment-related bleeding. In this study, we examined platelet production and apoptosis to understand the cause of thrombocytopenia in patients with HAPC. The classification of myeloid-derived megakaryocytes (MKs) in HAPC patients was mainly granular MKs rather than mature MKs, suggesting impaired differentiation and maturation. However, the total number of MKs and newly generated reticulated platelets in the peripheral blood increased, indicating sufficient platelet generation in HAPC thrombocytopenia. Increased platelet apoptosis may be one of the causes of thrombocytopenia. Platelet activation and GP1bα pathway activation induced by thrombin and von Willebrand factor can lead to platelet apoptosis. Platelet production was not reduced in patients with HAPC, whereas platelet apoptosis was associated with thrombocytopenia. These findings provide a rationale for considering the bleeding risk in HAPC patient while treating thrombotic diseases. What is the context?