Despite the accumulation of cisplatin in proximal tubules, direct visualization of the surrounding peritubular microcirculation, including its change in cisplatin-induced acute kidney injury (AKI), is lacking. Here, using fluorescence and cellular angiography through video-rate high-resolution intravital microscopy, progressive disturbance of peritubular microcirculation in cisplatin-induced AKI in mice was demonstrated. Fluorescence angiography revealed increasing perfusion defects, with a stepwise rise in time to peak (TTP), originating from capillaries surrounding S1 segments. Cellular angiography demonstrated a progressive decrease in the velocity and track length of individual erythrocytes during AKI progression, accompanied by a sequential decrease in the functional capillary ratio (FCR). Changes in the perfusion area, TTP, and FCR preceded significant changes in blood urea nitrogen and cystatin C, suggesting the potential for early diagnosis. Although neutrophil infiltration near proximal tubules increased throughout the progression, it did not cause obstruction of the peritubular microcirculation. Depletion of neutrophils increased mortality due to systemic side effects, whereas functional inactivation of neutrophils using an anti-CD11b antibody improved peritubular microcirculation in cisplatin-induced AKI. This approach enables direct visualization and quantification of peritubular microcirculation and immune cell dynamics, providing insights into renal pathophysiology and potential therapeutic strategies.

Superparamagnetic iron oxide nanoparticles (SPIONs) are promising contrast agents for imaging-guided cancer therapies. However, challenges such as the requirement for a high alternating magnetic field (AMF), dosage limitations, and suboptimal imaging contrast have hindered their practical applications. Methods: First, the optimal doping ratio of Mn and Zn in MnxZn1-xFe2O4 nanoparticles synthesized using a modified high-temperature thermal decomposition method (mHTTD) was determined. Then, the magnetic and physical properties of the optimal 7-nm Mn0.5Zn0.5Fe2O4 SPIONs were systematically and comprehensively characterized via hysteresis measurements, dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray absorption fine structure (XAFS) spectroscopy, and X-ray absorption near edge structure (XANES) spectroscopy. Next, the stability, biosafety, biocompatibility, and theranostic performance of 7-nm Mn0.5Zn0.5Fe2O4 SPIONs in magnetic hyperthermia therapy (MHT) were evaluated by in vivo and in vitro studies involving mouse models, magnetic resonance imaging (MRI), and bioassays. The results were then compared with those for conventional SPIONs. Results: Under an AMF of 140 Oe at 100 kHz, 7-nm Mn0.5Zn0.5Fe2O4 SPIONs demonstrated significantly higher heat production than conventional SPIONs. Following surface modification with methoxy-PEG-silane, PEGylated 7-nm Mn0.5Zn0.5Fe2O4 SPIONs showed excellent monodispersity and magnetic properties, with an exceptionally high T2 relaxivity (r2). Conclusions: The high in vitro and in vivo theranostic performance of PEGylated 7-nm Mn0.5Zn0.5Fe2O4 SPIONs as efficient and stable contrast agents for treating glioblastoma, encompassing strengthened magnetic hyperthermia, activated anti-tumor immunity, and remarkable T2 contrast enhancement, underscores the potential of precisely designed ferrites to concurrently enhance the T2 contrast and magnetocaloric properties for optimal theranostic outcomes. Our study provides a compelling rationale for the development of tailored magnetic nanoprobes for improved glioblastoma theranostics.
© The author(s).

The bone marrow microenvironment is a critical regulator of haematopoietic stem cell self-renewal and fate1. Although it is appreciated that ageing, chronic inflammation and other insults compromise bone marrow function and thereby negatively affect haematopoiesis2, it is not known whether different bone compartments exhibit distinct microenvironmental properties and functional resilience. Here we use imaging, pharmacological approaches and mouse genetics to uncover specialized properties of bone marrow in adult and ageing skull. Specifically, we show that the skull bone marrow undergoes lifelong expansion involving vascular growth, which results in an increasing contribution to total haematopoietic output. Furthermore, skull is largely protected against major hallmarks of ageing, including upregulation of pro-inflammatory cytokines, adipogenesis and loss of vascular integrity. Conspicuous rapid and dynamic changes to the skull vasculature and bone marrow are induced by physiological alterations, namely pregnancy, but also pathological challenges, such as stroke and experimental chronic myeloid leukaemia. These responses are highly distinct from femur, the most extensively studied bone marrow compartment. We propose that skull harbours a protected and dynamically expanding bone marrow microenvironment, which is relevant for experimental studies and, potentially, for clinical treatments in humans.
© 2024. The Author(s).

Introduction: The classically defined two retinal microglia layers are distributed in inner and outer plexiform layers. Although there are some reports that retinal microglia are also superficially located around the ganglion cell layer (GCL) in contact with the vitreous, there has been a lack of detailed descriptions and not fully understood yet. Methods: We visualized the microglial layers by using CX3CR1-GFP (C57BL6) transgenic mice with both healthy and disease conditions including NaIO3-induced retinal degeneration models and IRBP-induced auto-immune uveitis models. Result: We found the GCL microglia has two subsets; peripheral (pph) microglia located on the retinal parenchyma and BAM (CNS Border Associated Macrophage) which have a special stretched phenotype only located on the surface of large retinal veins. First, in the pph microglia subset, but not in BAM, Galectin-3 and LYVE1 are focally expressed. However, LYVE1 is specifically expressed in the amoeboid or transition forms, except the typical dendritic morphology in the pph microglia. Second, BAM is tightly attached to the surface of the retinal veins and has similar morphology patterns in both the healthy and disease conditions. CD86+ BAM has a longer process which vertically passes the proximal retinal veins. Our data helps decipher the basic anatomy and pathophysiology of the retinal microglia in the GCL. Discussion: Our data helps decipher the basic anatomy and pathophysiology of the retinal microglia in the GCL.
Copyright © 2024 Jeon, Park, Kim, Kong, Kim, Yang, Lee, Kim, Kim and Kim.

The bone marrow microenvironment is a critical regulator of hematopoietic stem cell self-renewal and fate. While it is appreciated that aging, chronic inflammation and other insults compromise bone marrow function and thereby negatively affect hematopoiesis, it is not known whether different bone compartments exhibit distinct microenvironmental properties and functional resilience. Here, we have employed imaging, pharmacological approaches, and mouse genetics to uncover specialized and highly surprising properties of bone marrow in adult and aging skull. Specifically, we show that the skull bone marrow undergoes lifelong expansion involving vascular growth, which results in an increasing contribution to total hematopoietic output. Furthermore, skull is largely protected against major hallmarks of aging, including upregulation of inflammatory cytokines, adipogenesis and loss of vascular integrity. Striking dynamic and rapid changes to the skull vasculature and bone marrow are induced by physiological alterations, namely pregnancy, but also pathological challenges, such as stroke and experimental chronic myeloid leukemia. These responses are highly distinct from femur, the most extensively studied bone marrow compartment. We propose that skull harbors a protected and dynamically expanding bone marrow microenvironment, which is relevant for experimental studies but, potentially, also clinical treatments in humans.