Oxidative phosphorylation (OXPHOS) in the mitochondrial inner membrane is a therapeutic target in many diseases. Neural stem cells (NSCs) show progress in improving mitochondrial dysfunction in the central nervous system (CNS). However, translating neural stem cell-based therapies to the clinic is challenged by uncontrollable biological variability or heterogeneity, hindering uniform clinical safety and efficacy evaluations. We propose a systematic top-down design based on membrane self-assembly to develop neural stem cell-derived oxidative phosphorylating artificial organelles (SAOs) for targeting the central nervous system as an alternative to NSCs. We construct human conditionally immortal clone neural stem cells (iNSCs) as parent cells and use a streamlined closed operation system to prepare neural stem cell-derived highly homogenous oxidative phosphorylating artificial organelles. These artificial organelles act as biomimetic organelles to mimic respiration chain function and perform oxidative phosphorylation, thus improving ATP synthesis deficiency and rectifying excessive mitochondrial reactive oxygen species production. Conclusively, we provide a framework for a generalizable manufacturing procedure that opens promising prospects for disease treatment.
© 2024. The Author(s).

Early detection of cancer recurrence using specific biomarkers remains a clinically unmet need, although methodologies for monitoring tumor markers, cell-free DNA, and circulating tumor cells have been established for decades. Tumor recurrence develops in metastatic or dormant cancer cells under continuous immune surveillance. Alterations in the population and function of immune cells may contribute to cancer recurrence. Here, we utilized an animal model to imitate breast tumor recurrence after surgical resection and investigated the abundance and gene expression profiles of immune cells using NanoString analysis. Bioinformatic analysis of a published single-cell RNA sequencing database of myeloid-derived suppressor cells (MDSCs) was performed to identify common targets between the two studies. Identified biomarkers were validated using human peripheral blood mononuclear cell (PBMC) datasets. The inhibitory effect of MDSCs on T-cell proliferation was assessed in vitro. Our data demonstrated that the number of MDSCs significantly increased during recurrence. Comparison of our NanoString data with a single-cell RNA sequencing dataset of MDSCs in another spontaneous breast cancer model identified colony-stimulating factor 3 receptor (Csf3r)-positive MDSCs as a potential marker for predicting tumor relapse. We validated our findings using two previously published PBMC databases of patients with breast cancer with or without recurrence and confirmed the elevated MDSC gene signature and CSF3R expression in patients with tumor recurrence. 35 patients with breast cancer were also included in our study, that patients with higher levels of CSF3R had worse survival. In vitro experiments demonstrated that Csf3r + MDSCs exhibited enhanced reactive oxygen species (ROS) levels and robust T-cell suppression ability. We conclude that an increase in CSF3R + MDSCs is a potential biomarker for early detection of tumor recurrence in patients with breast cancer.
AJCR Copyright © 2024.

The molecular dynamics of pancreatic ductal adenocarcinoma (PDAC) under chemotherapy remain incompletely understood. The widespread use of neoadjuvant chemotherapy (NAC) provides a unique opportunity to investigate PDAC samples post-chemotherapy. Leveraging a cohort from Fudan University Shanghai Cancer Center, encompassing PDAC samples with and without exposure to neoadjuvant albumin-bound paclitaxel and gemcitabine (AG), we have compiled data from single-cell and spatial transcriptomes, proteomes, bulk transcriptomes, and metabolomes, deepening our comprehension of the molecular changes in PDACs in response to chemotherapy. Metabolic flux analysis reveals that NAC induces a reprogramming of PDAC metabolic patterns and enhances immunogenicity. Notably, NAC leads to the downregulation of glycolysis and the upregulation of CD36. Tissue microarray analysis demonstrates that high CD36 expression is linked to poorer survival in patients receiving postoperative AG. Targeting CD36 synergistically improves the PDAC response to AG both in vitro and in vivo, including patient-derived preclinical models.
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Acute respiratory distress syndrome (ARDS) is a common lung disorder that involves severe inflammatory damage in the pulmonary barrier, but the underlying mechanisms remain elusive. Here, we demonstrated that pulmonary macrophages originating from ARDS patients and mice caused by bacteria were characterized by increased expression of ferroportin (FPN). Specifically deleting FPN in myeloid cells conferred significant resistance to bacterial infection with improved survival by decreasing extracellular bacterial growth and preserving pulmonary barrier integrity in mice. Mechanistically, macrophage FPN deficiency not only limited the availability of iron to bacteria, but also promoted tissue restoration via growth factor amphiregulin, which is regulated by cellular iron-activated Yes-associated protein signaling. Furthermore, pharmacological treatment with C-Hep, the self-assembled N-terminally cholesterylated minihepcidin that functions in the degradation of macrophage FPN, protected against bacteria-induced lung injury. Therefore, therapeutic strategies targeting the hepcidin-FPN axis in macrophages may be promising for the clinical treatment of acute lung injury.
© 2022 The Author(s).

Since paroxysmal nocturnal haemoglobinuria (PNH) was first described in 1881, the diagnosis and follow-up patients diagnosed with the illness has remained an area of concern, with several different techniques of varying sensitivity having been described in the literature for both the diagnosis and monitoring treatment of the disease. PNH is a rare and life-threatening disease that manifests symptoms of haemolytic anaemia. Hence, a quick and reliable technique for precise diagnosis would be crucial. PNH patients who have previously been diagnosed with aplastic anaemia or myelodysplastic syndrome carry small PNH clones and for more than a century traditional method with low sensitivity was used for such patients. In 2010, the International Clinical Cytometry Society described a highly sensitive method for detection and quantification of different types of PNH clones using multi-colour flow cytometry. In this method, a three-colour flow cytometer is essential to detect PNH affected cells amongst monocytes and granulocytes. This started a new era in the diagnosis of patients who carry small clones of PNH cells. Before this, flow cytometric analysis was used only for detection of PNH cells amongst erythrocytes. By using flow cytometry instruments with more light sources, the sensitivity of detection and quantification of PNH clones would be augmented. However, standardisation and crosstalk compensation would be the most concerning issue. For the first time in Iran, we set up and standardised multi-colour flow cytometry technique to detect PNH cells in erythrocytes and leukocytes at Payvand medical laboratory.
© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.