Infiltrating plasma cells maintain glioblastoma stem cells through IgG-Tumor binding.

Glioblastoma is a highly aggressive primary brain tumor with glioblastoma stem cells (GSCs) enforcing the intra-tumoral hierarchy. Plasma cells (PCs) are critical effectors of the B-lineage immune system, but their roles in glioblastoma remain largely unexplored. Here, we leverage single-cell RNA and B cell receptor sequencing of tumor-infiltrating B-lineage cells and reveal that PCs are aberrantly enriched in the glioblastoma-infiltrating B-lineage population, experience low level of somatic hypermutation, and are associated with poor prognosis.

Reactivating PTEN to impair glioma stem cells by inhibiting cytosolic iron-sulfur assembly.

Glioblastoma, the most lethal primary brain tumor, harbors glioma stem cells (GSCs) that not only initiate and maintain malignant phenotypes but also enhance therapeutic resistance. Although frequently mutated in glioblastomas, the function and regulation of PTEN in PTEN-intact GSCs are unknown. Here, we found that PTEN directly interacted with MMS19 and competitively disrupted MMS19-based cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) machinery in differentiated glioma cells.

Hypoxanthine phosphoribosyl transferase 1 metabolizes temozolomide to activate AMPK for driving chemoresistance of glioblastomas.

Temozolomide (TMZ) is a standard treatment for glioblastoma (GBM) patients. However, TMZ has moderate therapeutic effects due to chemoresistance of GBM cells through less clarified mechanisms. Here, we demonstrate that TMZ-derived 5-aminoimidazole-4-carboxamide (AICA) is converted to AICA ribosyl-5-phosphate (AICAR) in GBM cells.

Dual Role of CXCL8 in Maintaining the Mesenchymal State of Glioblastoma Stem Cells and M2-Like Tumor-Associated Macrophages.

Purpose: The dynamic interplay between glioblastoma stem cells (GSC) and tumor-associated macrophages (TAM) sculpts the tumor immune microenvironment (TIME) and promotes malignant progression of glioblastoma (GBM). However, the mechanisms underlying this interaction are still incompletely understood. Here, we investigate the role of CXCL8 in the maintenance of the mesenchymal state of GSC populations and reprogramming the TIME to an immunosuppressive state.

Sterol regulatory element-binding protein 2 maintains glioblastoma stem cells by keeping the balance between cholesterol biosynthesis and uptake.

Background: Glioblastomas (GBMs) display striking dysregulation of metabolism to promote tumor growth. Glioblastoma stem cells (GSCs) adapt to regions of heterogeneous nutrient availability, yet display dependency on de novo cholesterol biosynthesis. The transcription factor Sterol Regulatory Element-Binding Protein 2 (SREBP2) regulates cholesterol biosynthesis enzymes and uptake receptors.

Role of Ezrin in Asthma-Related Airway Inflammation and Remodeling.

Ezrin is an actin binding protein connecting the cell membrane and the cytoskeleton, which is crucial to maintaining cell morphology, intercellular adhesion, and cytoskeleton remodeling. Asthma involves dysfunction of inflammatory cells, cytokines, and airway structural cells. Recent studies have shown that ezrin, whose function is affected by extensive phosphorylation and protein interactions, is closely associated with asthma, may be a therapeutic target for asthma treatment.

Salidroside reduces neuropathology in Alzheimer's disease models by targeting NRF2/SIRT3 pathway.

Background: Neurite dystrophy is a pathologic hallmark of Alzheimer's disease (AD). However, drug discovery targeting neurite protection in AD remains largely unexplored.

Methods: Aβ-induced neurite and mitochondrial damage assays were used to evaluate Aβ toxicity and the neuroprotective efficacy of a natural compound salidroside (SAL).

Fumarate inhibits PTEN to promote tumorigenesis and therapeutic resistance of type2 papillary renal cell carcinoma.

Fumarate is an oncometabolite. However, the mechanism underlying fumarate-exerted tumorigenesis remains unclear. Here, utilizing human type2 papillary renal cell carcinoma (PRCC2) as a model, we show that fumarate accumulates in cells deficient in fumarate hydratase (FH) and inhibits PTEN to activate PI3K/AKT signaling.

A new approach for reducing pollutants level: a longitudinal cohort study of physical exercises in young people.

Background: The present study aimed to evaluate the elimination of three common pollutants (dimethoate, benzo(a)pyrene (BaP) and bisphenol A (BPA) by different physical exercises and to assess the possible factors which could affect the pollutants elimination.

Methods: A total of 200 individuals who chose different kinds of exercises in accordance to their own wish were recruited. The levels of urinary pollutants were measured using β-glucuronidase hydrolysis followed by a high-performance liquid chromatography tandem mass spectrometry-based method.

Oleanolic Acid (OA) Targeting UNC5B Inhibits Proliferation and EMT of Ovarian Cancer Cell and Increases Chemotherapy Sensitivity of Niraparib.

Objective: To investigate the effect of OA on proliferation, migration, and epithelial-mesenchymal transition (EMT) of ovarian cancer cells by inhibiting UNC5B and to study its mechanism.

Methods: TCGA database was used to analyze the expression of UNC5B in ovarian cancer and its relationship with prognosis. The expression of UNC5B in ovarian cancer cells was detected by qPCR assay.

Urinary levels of dimethoate, bisphenol A and benzo[a]pyrene in first-year students of Hohai University from different geographical regions.

Background: The objective of this study was to detect the urinary levels of dimethoate, benzo(a) pyrene (BaP), and bisphenol A (BPA) in first-year Hohai University students with different geographic origins.

Methods: First-morning urine samples were collected from 540 healthy freshmen aged 17 to 19 years. Chemical levels were measured using β-glucuronidase hydrolysis followed by a high-performance liquid chromatography-tandem mass spectrometry-based method.

A Buthus martensii Karsch scorpion sting targets Nav1.7 in mice and mimics a phenotype of human chronic pain.

Gain-of-function and loss-of-function mutations in Nav1.7 cause chronic pain and pain insensitivity, respectively. The preferential expression of Nav1.

Repeated Herbal Acupoint Sticking Relieved the Recurrence of Allergic Asthma by Regulating the Th1/Th2 Cell Balance in the Peripheral Blood.

Allergic asthma is an inflammatory disease involving the Th1/Th2 cell imbalance in the peripheral blood. Repeated herbal acupoint sticking (RHAS) has been used for hundreds of years in China to relieve the recurrence of allergic asthma, and it is still practiced today. Thus, we explored the effect on allergic asthma relapse and the underlying immunoregulatory mechanism in this study.

Tyrosine nitrations impaired intracellular trafficking of FSHR to the cell surface and FSH-induced Akt-FoxO3a signaling in human granulosa cells.

Many infertile women suffered from poor ovarian response, and increased reactive oxygen species with age might mediate the poor ovarian response to FSH. In this study, we collected follicular fluids and isolated granulosa cells from female patients. Increased levels of peroxynitrite, tyrosine nitrations of FSH receptor (FSHR) and apoptosis were obviously detectable with decreased FSHR protein expressions in granulosa cells of the poor ovarian responders.

Glutathione S-transferases P1 protects breast cancer cell from adriamycin-induced cell death through promoting autophagy.

Glutathione S-transferases P1 (GSTP1) is a phase II detoxifying enzyme and increased expression of GSTP1 has been linked with acquired resistance to anti-cancer drugs. However, most anticancer drugs are not good substrates for GSTP1, suggesting that the contribution of GSTP1 to drug resistances might not be dependent on its capacity to detoxify chemicals or drugs. In the current study, we found a novel mechanism by which GSTP1 protects human breast cancer cells from adriamycin (ADR)-induced cell death and contributes to the drug resistance.

Inhibition of GGPPS1 attenuated LPS-induced acute lung injury and was associated with NLRP3 inflammasome suppression.

Inhibition of the mevalonate pathway using statins has been shown to be beneficial in the treatment of acute lung injury (ALI). Here, we investigated whether partial inhibition of this pathway by targeting geranylgeranyl pyrophosphate synthase large subunit 1 (GGPPS1), a catalase downstream of the mevalonate pathway, was effective at treating lung inflammation in ALI. Lipopolysaccharide (LPS) was intratracheally instilled to induce ALI in lung-specific GGPPS1-knockout and wild-type mice.

Integrative proteomics and immunochemistry analysis of the factors in the necrosis and repair in acetaminophen-induced acute liver injury in mice.

Acetaminophen (APAP) overdose-induced acute liver injury (AILI) is a significant clinical problem worldwide, the hepatotoxicity mechanisms are well elucidated, but the factors involved in the necrosis and repair still remain to be investigated. APAP was injected intraperitoneally in male Institute of Cancer Research (ICR) mice. Quantitative proteome analysis of liver tissues was performed by 2-nitrobenzenesulfenyl tagging, two-dimensional-nano high-performance liquid chromatography separation, and matrix-assisted laser desorption/ionization-time of flight mass spectrometry analysis.

Quantitative Proteomic Analysis Reveals That Arctigenin Alleviates Concanavalin A-Induced Hepatitis Through Suppressing Immune System and Regulating Autophagy.

Concanavalin A-induced autoimmune hepatitis is a well-established experimental model for immune-mediated liver injury. It has been widely used in the therapeutic studies of immune hepatitis. The in-depth analysis of dysregulated proteins from comparative proteomic results indicated that the activation of immune system resulted in the deregulation of autophagy.

Modulations of Keap1-Nrf2 signaling axis by TIIA ameliorated the oxidative stress-induced myocardial apoptosis.

Mounting evidence has strongly implicated oxidative stress in the development of cardiac dysfunction, and myocardial apoptosis contributes to the pathogenesis of heart failure. Quantitative cardiac proteomics data revealed that pressure load by TAC resulted in a significant decline in mitochondrial metabolic activity, where TIIA (Tanshinone IIA sulfonate) treatment reversed it in vivo, which might be mediated by Nrf2. In NRVMs, TIIA treatment ameliorated HO-induced caspase-3/9 activations through the suppression of p38 and mTOR signaling pathways, where caspase-mediated cleavage of YY1 and PARP resulted in the defects in mitochondrial biogenesis and DNA repair, and this event finally led to cardiomyocyte apoptosis.

Click-Chemistry-Mediated Rapid Microbubble Capture for Acute Thrombus Ultrasound Molecular Imaging.

Bioorthogonal coupling chemistry has been studied as a potentially advantageous approach for molecular imaging because it offers rapid, efficient, and strong binding, which might also benefit stability, production, and chemical conjugation. The inverse-electron-demand Diels-Alder reaction between a 1,2,4,5-tetrazine and trans-cyclooctene (TCO) is an example of a highly selective and rapid bioorthogonal coupling reaction that has been used successfully to prepare targeted molecular imaging probes. Here we report a fast, reliable, and highly sensitive approach, based on a two-step pretargeting bioorthogonal approach, to achieving activated-platelet-specific CD62p-targeted thrombus ultrasound molecular imaging.

Hsp90β is involved in the development of high salt-diet-induced nephropathy via interaction with various signalling proteins.

A high-salt diet often leads to a local intrarenal increase in renal hypoxia and oxidative stress, which are responsible for an excess production of pathogenic substances. Here, Wistar Kyoto/spontaneous hypertensive (WKY/SHR) rats fed a high-salt diet developed severe proteinuria, resulting from pronounced renal inflammation, fibrosis and tubular epithelial cell apoptosis. All these were mainly non-pressure-related effects.

Identification of citrullinated peptides in the synovial fluid of patients with rheumatoid arthritis using LC-MALDI-TOF/TOF.

The objective of the study is to investigate potential citrullinated autoantigens as targets of anti-citrullinated protein antibodies (ACPAs) response in synovial fluids (SFs) of patients with rheumatoid arthritis (RA). SFs from six RA patients and six osteoarthritis (OA) patients as controls were collected. The citrullinated proteins in SFs were extracted by immunoprecipitation with rabbit anti-citrulline antibodies.

Neuroprotection by Polynitrogen Manganese Complexes: Regulation of Reactive Oxygen Species-Related Pathways.

Cell death in the central nervous system causes neurologic diseases, in which reactive oxygen species (ROS) play a critical role by either inducing cellular oxidative stress or by increasing the cell tolerance against insult. Neurologic diseases may potentially be treated by regulating ROS levels in a certain range with small molecules. We studied preconditioning with two polynitrogen manganese complexes (1 and 2) to regulate intracellular ROS levels in the protection of both the differentiated rat pheochromocytoma cell line (PC12 cells) and neurons against H2O2-induced apoptosis.