Pseudohypoxic stabilization of HIF1α via cyclophilin D suppression promotes melanoma metastasis.

Stabilization of hypoxia-inducible factor 1 alpha (HIF1α), which plays a pivotal role in regulating cellular responses to insufficient oxygen, is implicated in cancer progression, particularly epithelial-mesenchymal transition and metastatic dissemination. Despite its crucial role in tumorigenesis, the precise mechanisms governing HIF1α stabilization under varying tumor microenvironmental conditions are not fully understood. In this study, we show that stabilization of HIF1α in metastasizing melanoma under mild hypoxia is regulated primarily by mitochondrial reactive oxygen species (ROS) rather than by reduced oxygen levels.

Chitosan Nanoparticle-Encapsulated Grown on Germinated Reduces Type II Alveolar Epithelial Cell Apoptosis in PM-Induced Lung Injury.

Chitosan nanoparticles (CNPs) were synthesized in this study to enhance the limited bioactivity and stability of grown on germinated (GRC) and effectively deliver it to target tissues. Under optimized conditions, stable encapsulation of GRC was achieved by setting the chitosan (CHI)-to-tripolyphosphate (TPP) ratio to 4:1 and adjusting the pH of TPP to 2, resulting in a zeta potential of +22.77 mV, which indicated excellent stability.

Continuous Tracking for Effective Tackling: Ad5/35 Platform-Based JN1 Lineage Vaccines Development in Response to Evolving SARS-CoV-2 Variants.

The SARS-CoV-2 virus is continuously evolving, such that JN.1 and its subvariants, including KP.2, KP.

A microglial kinase ITK mediating neuroinflammation and behavioral deficits in traumatic brain injury.

Microglia-mediated neuroinflammation has been implicated in the neuropathology of traumatic brain injuries (TBI). Recently, the expression of interleukin-2-inducible T-cell kinase (ITK) has been detected in brain microglia, regulating their inflammatory activities. However, the role of microglial ITK in TBI has not been investigated.

Exploratory profiling of metabolites in cerebrospinal fluid using a commercially available targeted LC-MS based metabolomics kit to discriminate leptomeningeal metastasis.

Background: Leptomeningeal metastasis (LM) is a devastating complication of cancer that is difficult to treat. Thus, early diagnosis is essential for LM patients. However, cerebrospinal fluid (CSF) cytology has low sensitivity, and imaging approaches are ineffective.

RNA-binding proteins and exoribonucleases modulating miRNA in cancer: the enemy within.

Recent progress in the investigation of microRNA (miRNA) biogenesis and the miRNA processing machinery has revealed previously unknown roles of posttranscriptional regulation in gene expression. The molecular mechanistic interplay between miRNAs and their regulatory factors, RNA-binding proteins (RBPs) and exoribonucleases, has been revealed to play a critical role in tumorigenesis. Moreover, recent studies have shown that the proliferation of hepatocellular carcinoma (HCC)-causing hepatitis C virus (HCV) is also characterized by close crosstalk of a multitude of host RBPs and exoribonucleases with miR-122 and its RNA genome, suggesting the importance of the mechanistic interplay among these factors during the proliferation of HCV.

Clinical Relevance of Plasma Prolylcarboxypeptidase Level in Patients with Idiopathic Acute Optic Neuritis.

This study evaluated the plasma concentration of prolylcarboxypeptidase (PRCP) and its clinical relevance in patients with idiopathic acute optic neuritis (ON). We investigated the expression of PRCP in the optic nerves of experimental autoimmune optic neuritis (EAON)-induced mice. Peripheral blood samples were collected from ON patients (n = 20) and healthy controls (n = 20).

Extracellular Vesicles from Cerebrospinal Fluid of Leptomeningeal Metastasis Patients Deliver MiR-21 and Induce Methotrexate Resistance in Lung Cancer Cells.

Leptomeningeal metastasis (LM) is a common and fatal complication of advanced non-small cell lung cancer (NSCLC) caused by the spread of malignant cells to the leptomeninges and cerebrospinal fluid (CSF). While intra-CSF methotrexate (MTX) chemotherapy can improve prognosis, eventual MTX resistance deters continued chemotherapy. Recent studies have shown that increased miRNA-21 (miR-21) expression in the CSF of patients with LM after intraventricular MTX-chemotherapy is associated with poor overall survival; however, the molecular mechanisms underlying this resistance are poorly understood.

Strategy to develop broadly effective multivalent COVID-19 vaccines against emerging variants based on Ad5/35 platform.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron strain has evolved into highly divergent variants with several sub-lineages. These newly emerging variants threaten the efficacy of available COVID-19 vaccines. To mitigate the occurrence of breakthrough infections and re-infections, and more importantly, to reduce the disease burden, it is essential to develop a strategy for producing updated multivalent vaccines that can provide broad neutralization against both currently circulating and emerging variants.

Boosting with variant-matched adenovirus-based vaccines promotes neutralizing antibody responses against SARS-CoV-2 Omicron sublineages in mice.

Global spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron subvariants, such as BA.4, BA.5 and XBB.

Analogous Design of a Microlayered Silicon Oxide-Based Electrode to the General Electrode Structure for Thin-Film Lithium-Ion Batteries.

Development of miniaturized thin-film lithium-ion batteries (TF-LIBs) using vacuum deposition techniques is crucial for low-scale applications, but addressing low energy density remains a challenge. In this work, structures analogous to SiO-based thin-film electrodes are designed with close resemblance to traditional LIB slurry formulations including active material, conductive agent, and binder. The thin-film is produced using mid-frequency sputtering with a single hybrid target consisting of SiO nanoparticles, carbon nanotubes, and polytetrafluoroethylene.

Utilizing databases for astrocyte secretome research.

Introduction: Astrocytes are the most abundant cell type in the central nervous system (CNS). They play a pivotal role in supporting neuronal function and maintaining homeostasis by releasing a variety of bioactive proteins, collectively known as the astrocyte secretome. Investigating secretome provides insights into the molecular mechanisms underlying astrocyte function and dysfunction, as well as novel strategies to prevent and treat diseases affecting the CNS.

Cross-talk between PARN and EGFR-STAT3 Signaling Facilitates Self-Renewal and Proliferation of Glioblastoma Stem Cells.

Unlabelled: Glioblastoma is the most common type of malignant primary brain tumor and displays highly aggressive and heterogeneous phenotypes. The transcription factor STAT3 has been reported to play a key role in glioblastoma malignancy. Thus, discovering targets and functional downstream networks regulated by STAT3 that govern glioblastoma pathogenesis may lead to improved treatment strategies.

Analyzing the glial proteome in Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, memory loss, and changes in behavior. Accumulating evidence indicates that dysfunction of glial cells, including astrocytes, microglia, and oligodendrocytes, may contribute to the development and progression of AD. Large-scale analysis of glial proteins sheds light on their roles in cellular processes and diseases.

Incorporation of Cell-Adhesive Proteins in 3D-Printed Lipoic Acid-Maleic Acid-Poly(Propylene Glycol)-Based Tough Gel Ink for Cell-Supportive Microenvironment.

In extrusion-based 3D printing, the use of synthetic polymeric hydrogels can facilitate fabrication of cellularized and implanted scaffolds with sufficient mechanical properties to maintain the structural integrity and physical stress within the in vivo conditions. However, synthetic hydrogels face challenges due to their poor properties of cellular adhesion, bioactivity, and biofunctionality. New compositions of hydrogel inks have been designed to address this limitation.

A multiplexed siRNA screen identifies key kinase signaling networks of brain glia.

The dynamic behaviors of brain glial cells in various neuroinflammatory conditions and neurological disorders have been reported; however, little is known about the underlying intracellular signaling pathways. Here, we developed a multiplexed kinome-wide siRNA screen to identify the kinases regulating several inflammatory phenotypes of mouse glial cells in culture, including inflammatory activation, migration, and phagocytosis of glia. Subsequent proof-of-concept experiments involving genetic and pharmacological inhibitions indicated the importance of T-cell receptor signaling components in microglial activation and a metabolic shift from glycolysis to oxidative phosphorylation in astrocyte migration.

PLK1-ELAVL1/HuR-miR-122 signaling facilitates hepatitis C virus proliferation.

The liver-specific microRNA, miR-122, plays an essential role in the propagation of hepatitis C virus (HCV) by binding directly to the 5'-end of its genomic RNA. Despite its significance for HCV proliferation, the host factors responsible for regulating miR-122 remain largely unknown. In this study, we identified the cellular RNA-binding protein, ELAVL1/HuR (embryonic lethal-abnormal vision-like 1/human antigen R), as critically contributing to miR-122 biogenesis by strong binding to the 3'-end of miR-122.

Lipocalin-2 Is a Key Regulator of Neuroinflammation in Secondary Traumatic and Ischemic Brain Injury.

Reactive glial cells are hallmarks of brain injury. However, whether these cells contribute to secondary inflammatory pathology and neurological deficits remains poorly understood. Lipocalin-2 (LCN2) has inflammatory and neurotoxic effects in various disease models; however, its pathogenic role in traumatic brain injury remains unknown.

Soluble ANPEP Released From Human Astrocytes as a Positive Regulator of Microglial Activation and Neuroinflammation: Brain Renin-Angiotensin System in Astrocyte-Microglia Crosstalk.

Astrocytes are major supportive glia and immune modulators in the brain; they are highly secretory in nature and interact with other cell types via their secreted proteomes. To understand how astrocytes communicate during neuroinflammation, we profiled the secretome of human astrocytes following stimulation with proinflammatory factors. A total of 149 proteins were significantly upregulated in stimulated astrocytes, and a bioinformatics analysis of the astrocyte secretome revealed that the brain renin-angiotensin system (RAS) is an important mechanism of astrocyte communication.

From Molecular Mechanisms to Therapeutics: Understanding MicroRNA-21 in Cancer.

MicroRNAs (miRNAs) are small noncoding RNAs that play an important role in regulating gene expression at a posttranscriptional level. As one of the first discovered oncogenic miRNAs, microRNA-21 (miR-21) has been highlighted for its critical role in cancers, such as glioblastoma, pancreatic adenocarcinoma, non-small cell lung cancer, and many others. MiR-21 targets many vital components in a wide range of cancers and acts on various cellular processes ranging from cancer stemness to cell death.