NOTCH3 Mutation Causes Glymphatic Impairment and Promotes Brain Senescence in CADASIL.

Aims: The aim of this study is to investigate the role of glymphatic function of cerebral autosomal dominant arteriopathy, subcortical infarcts, and leukoencephalopathy (CADASIL), the most common monogenic small vessel disease caused by NOTCH3 mutation, and to explore potential therapeutic strategies to improve glymphatic function.

Methods: We assessed glymphatic influx and efflux function in CADASIL mouse models (Notch3) and correlated these findings with brain atrophy in CADASIL patients. We also investigated the underlying mechanisms of glymphatic impairment, focusing the expression of AQP4 in astrocytic endfeet.

Undifferentiated small round cell sarcoma of the parapharyngeal space in a 4.5-year-old patient:A rare case report.

This case report describes a 4.5-year-old girl diagnosed with a rare Undifferentiated Small Round Cell Sarcoma (USRCS) originating in the parapharyngeal space with multiple lung metastases. Diagnostic workups, including imaging, immunohistochemistry, and genetic sequencing, identified the tumor as an unclassified subtype of USRCS.

STING Activation in Macrophages and Microglia Drives Poststroke Inflammation: Implications for Neuroinflammatory Mechanisms and Therapeutic Interventions.

Background: Monocyte-derived macrophages and microglia initially adopt an anti-inflammatory phenotype following stroke but later transition to a pro-inflammatory state. The mechanisms underlying this phenotypic shift remain unclear. This study investigates the activation dynamics of molecular signaling pathways in macrophages and microglia after stroke.

Intra-cisterna-magna bevacizumab injection (ICM-BI) reproduces pathological alterations of cerebral small vessel diseases.

General modeling strategies for sporadic cerebral small blood vessel diseases (CSVDs) include limiting blood stream in large blood vessels and inducing systemic hypertension, in which small blood vessel deficit is either a secondary or concomitant pathology. In the current study, we introduce that intra-cisterna-magna Bevacizumab injection (ICM-BI) directly causes cerebral small blood vessel injury by neutralizing VEGF-A, the indispensable growth factor for angiogenesis. ICM-BI reproduces neuro-functional impairment, tight junction loss, cerebral micro-bleeds (CMBs), amyloid peptide accumulation, neuronal injury, white matter loss, and glial cell activation, which are common manifestations of sporadic CSVDs.

Bone marrow-derived mesenchymal stem cell ameliorates post-stroke enterobacterial translocation through liver-gut axis.

Background: Enterobacterial translocation is a leading contributor to fatal infection among patients with acute ischaemic stroke (AIS). Accumulative evidence suggests that mesenchymal stem cell (MSC) effectively ameliorates stroke outcomes. Whether MSC could inhibit post-stroke enterobacterial translocation remains elusive.

Myelin endocytosis by brain endothelial cells causes endothelial iron overload and oligodendroglial iron hunger in hypoperfusion-induced white matter injury.

Aims: Hypoperfusion induces significant white matter injury in cerebral vascular disorders, including arteriosclerotic cerebral small vessel disease (aCSVD), which is prevalent among the elderly. Iron transport by blood vessel endothelial cells (BVECs) from the periphery supports oligodendrocyte maturation and white matter repair. This study aims to elucidate the association between iron homeostasis changes and white matter injury severity, and explore the crosstalk between BVECs and oligodendroglial lineage cells.

Agomelatine promotes differentiation of oligodendrocyte precursor cells and preserves white matter integrity after cerebral ischemic stroke.

White matter injury contributes to neurological disorders after acute ischemic stroke (AIS). The repair of white matter injury is dependent on the re-myelination by oligodendrocytes. Both melatonin and serotonin antagonist have been proved to protect against post-stroke white matter injury.

Targeting Cyclin-Dependent Kinase 1 Induces Apoptosis and Cell Cycle Arrest of Activated Hepatic Stellate Cells.

Liver fibrosis is the integral process of chronic liver diseases caused by multiple etiologies and characterized by excessive deposition of extracellular matrix (ECM). During liver fibrosis, hepatic stellate cells (HSCs) transform into a highly proliferative, activated state, producing various cytokines, chemokines, and ECM. However, the precise mechanisms that license HSCs into the highly proliferative state remain unclear.

Comprehensive Profiling of Amine-Containing Metabolite Isomers with Chiral Phosphorus Reagents.

Metabolite isomers play diverse and crucial roles in various metabolic processes. However, in untargeted metabolomics analysis, it remains a great challenge to distinguish between the constitutional isomers and enantiomers of amine-containing metabolites due to their similar chemical structures and physicochemical properties. In this work, the triplex stable isotope -phosphoryl amino acids labeling (SIPAL) is developed to identify and relatively quantify the amine-containing metabolites and their isomers by using chiral phosphorus reagents coupled with high-resolution tandem mass spectroscopy.

Bone Marrow Mesenchymal Stem Cell-Derived Dermcidin-Containing Migrasomes enhance LC3-Associated Phagocytosis of Pulmonary Macrophages and Protect against Post-Stroke Pneumonia.

Pneumonia is one of the leading causes of death in patients with acute ischemic stroke (AIS). Antibiotics fail to improve prognosis of patients with post-stroke pneumonia, albeit suppressing infection, due to adverse impacts on the immune system. The current study reports that bone marrow mesenchymal stem cells (BM-MSC) downregulate bacterial load in the lungs of stroke mice models.

Exosomal EphA2 promotes tumor metastasis of triple-negative breast cancer by damaging endothelial barrier.

Many evidences show that exosomes play an important role in cancer development, invasion and metastasis. This study is based on the need to explore exosomal protein that promote breast cancer metastasis. We found that tyrosine kinase EphA2 was enriched in Triple-negative breast cancer -derived exosomes and it could disrupt the endothelial monolayer barrier through downregulating tight junction proteins of endothelial cells.

E2F1 Affects the Therapeutic Response to Neoadjuvant Therapy in Breast Cancer.

This study is aimed at screening genes for predicting the sensitivity response and favorable outcome of neoadjuvant therapy in breast cancer. We downloaded neoadjuvant therapy genetic data of breast cancer and separated it into the pathological complete response (pCR) group and the non-pCR group. Differential expression analysis was performed to select the differentially expressed genes (DEGs).

Mettl3-mediated mRNA mA modification controls postnatal liver development by modulating the transcription factor Hnf4a.

Hepatic specification and functional maturation are tightly controlled throughout development. N6-methyladenosine (mA) is the most abundant RNA modification of eukaryotic mRNAs and is involved in various physiological and pathological processes. However, the function of mA in liver development remains elusive.

The mA methyltransferase Mettl3 deficiency attenuates hepatic stellate cell activation and liver fibrosis.

Activation of hepatic stellate cells (HSCs) is a central driver of liver fibrosis. Previous investigations have identified various altered epigenetic landscapes during the cellular progression of HSC activation. N6-methyladenosine (mA) is the most abundant internal RNA modification in eukaryotic cells and is dynamically regulated under various physiological and pathophysiological conditions.

Deletion of Mettl3 at the Pro-B Stage Marginally Affects B Cell Development and Profibrogenic Activity of B Cells in Liver Fibrosis.

N6-methyladenosine (mA) modification plays a pivotal role in cell fate determination. Previous studies show that eliminating mA using dramatically impairs B cell development. However, whether disturbing mA modification at later stages affects B cell development and function remains elusive.

Filamin A Is a Potential Driver of Breast Cancer Metastasis Regulation of MMP-1.

Recurrent metastasis is a major fatal cause of breast cancer. Regretfully, the driving force and the molecular beneath have not been fully illustrated yet. In this study, a cohort of breast cancer patients with locoregional metastasis was recruited.

Human Wharton's jelly-derived mesenchymal stem cells alleviate concanavalin A-induced fulminant hepatitis by repressing NF-κB signaling and glycolysis.

Background: Fulminant hepatitis is a severe life-threatening clinical condition with rapid progressive loss of liver function. It is characterized by massive activation and infiltration of immune cells into the liver and disturbance of inflammatory cytokine production. Mesenchymal stem cells (MSCs) showed potent immunomodulatory properties.

The function and pathogenic mechanism of filamin A.

Filamin A(FLNa) is an actin-binding protein, which participates in the formation of the cytoskeleton, anchors a variety of proteins in the cytoskeleton and regulates cell adhesion and migration. It is involved in signal transduction, cell proliferation and differentiation, pseudopodia formation, vesicle transport, tumor resistance and genetic diseases by binding with interacting proteins. In order to fully elucidate the structure, function and pathogenesis of FLNa, we summarized all substances which directly or indirectly act on FLNa so far, upstream and downstream targets which having effect on it, signaling pathways and their functions.

Mesenchymal stem cells alleviate experimental immune-mediated liver injury via chitinase 3-like protein 1-mediated T cell suppression.

Liver diseases with different pathogenesis share common pathways of immune-mediated injury. Chitinase-3-like protein 1 (CHI3L1) was induced in both acute and chronic liver injuries, and recent studies reported that it possesses an immunosuppressive ability. CHI3L1 was also expressed in mesenchymal stem cells (MSCs), thus we investigates the role of CHI3L1 in MSC-based therapy for immune-mediated liver injury here.

Rapid Preparation of MWCNTs/Epoxy Resin Nanocomposites by Photoinduced Frontal Polymerization.

Due to their excellent mechanical and thermal properties and medium resistance, epoxy/carbon nanotubes and nanocomposites have been widely used in many fields. However, the conventional thermosetting process is not only time- and energy-consuming, but also causes the agglomeration of nanofillers, which leads to unsatisfactory properties of the obtained composites. In this study, multi-walled carbon nanotubes (MWCNTs)/epoxy nanocomposites were prepared using UV photoinduced frontal polymerization (PIFP) in a rapid fashion.

Generation of a DAPK1 knockout first (conditional ready) human embryonic stem cell line (ZSSYe001-A) by CRISPR-Cas9 technology.

Death-associated protein kinase 1 (DAPK1) is a Ca/calmodulin regulated Ser/Thr kinase involved in various cellular processes including cell death, autophagy and inflammation. Its dysregulation has been linked to tumour metastasis, anti-viral responses, Alzheimer's disease and other neurological disorders. To further investigate the role of DAPK1 in these processes, we generated a DAPK1 knockout first (conditional ready) human embryonic stem (hES) cell line in which the endogenous DAPK1 can be easily restored with expression of FLPe.

Myelin Oligodendrocyte Glycoprotein-IgG Contributes to Oligodendrocytopathy in the Presence of Complement, Distinct from Astrocytopathy Induced by AQP4-IgG.

Immunoglobulin G against myelin oligodendrocyte glycoprotein (MOG-IgG) is detectable in neuromyelitis optica spectrum disorder (NMOSD) without aquaporin-4 IgG (AQP4-IgG), but its pathogenicity remains unclear. In this study, we explored the pathogenic mechanisms of MOG-IgG in vitro and in vivo and compared them with those of AQP4-IgG. MOG-IgG-positive serum induced complement activation and cell death in human embryonic kidney (HEK)-293T cells transfected with human MOG.

CD44/CD24 phenotype predicts a poor prognosis in triple-negative breast cancer.

Cancer stem cells are enriched in triple-negative breast cancer (TNBC) tumor tissues, which present strong capacities of proliferation and tumorigenicity. The present study detected the distribution of cancer stem cell markers cluster of differentiation (CD)44/CD24 and analyzed the clinical outcomes of different CD44/CD24 phenotypes in patients with TNBC. Multivariate Cox regression analyses were performed with regard to the prognostic value of cancer stem cell markers CD44/CD24, aldehyde dehydrogenase 1 and other baseline clinical characteristics, including tumor size, lymph node involved, adjuvant chemotherapy, Ki-67, breast cancer susceptibility gene 1, cellular tumor antigen p53, vimentin and basal-like status.

Circulating long non-coding RNA AFAP1-AS1 is a potential diagnostic biomarker for non-small cell lung cancer.

Background: Recent studies have indicated that long non-coding RNA actin filament-associated protein 1 antisense RNA 1 (lncRNA AFAP1-AS1) was increased in non-small cell lung cancer and associated with unfavorable patient prognosis. AFAP1-AS1 also participates in promoting invasion and metastasis in non-small cell lung cancer cells. However, the diagnosis value of serum AFAP1-AS1 in non-small cell lung cancer was unclear.

Prognostic value of long non-coding RNA TUG1 in various tumors.

Taurine up-regulated gene 1 (TUG1) is a long non-coding RNA (lncRNA), has been reported that be dysregulated in various tumors, involved in proliferation and apoptosis in a variety of tumor cells. To detect the clinical significance of TUG1 expression in tumor patients, we carried out current systematic review and meta-analysis investigating its relation with the prognosis and clinicopathological features of cancers. A total of 15 studies comprise 1560 patients were analyzed.