Glioblastoma hijacks microglial gene expression to support tumor growth

Background: Glioblastomas are the most common and lethal primary brain tumors. Microglia, the resident immune cells of the brain, survey their environment and respond to pathogens, toxins, and tumors. Glioblastoma cells communicate with microglia, in part by releasing extracellular vesicles (EVs). Despite the presence of large numbers of microglia in glioblastoma, the tumors continue to grow, and these neuroimmune cells appear incapable of keeping the tumor in check. To understand this process, we analyzed gene expression in microglia interacting with glioblastoma cells. Methods: We used RNASeq of isolated microglia to analyze the expression patterns of genes involved in key microglial functions in mice with glioblastoma. We focused on microglia that had taken up tumor-derived EVs and therefore were within and immediately adjacent to the tumor. Results: We show that these microglia have downregulated expression of genes involved in sensing tumor cells and tumor-derived danger signals, as well as genes used for tumor killing. In contrast, expression of genes involved in facilitating tumor spread was upregulated. These changes appear to be in part EV-mediated, since intracranial injection of EVs in normal mice led to similar transcriptional changes in microglia. We observed a similar microglial transcriptomic signature when we analyzed datasets from human patients with glioblastoma. Conclusion: Our data define a microgliaGlioblastoma specific phenotype, whereby glioblastomas have hijacked gene expression in the neuroimmune system to favor avoiding tumor sensing, suppressing the immune response, clearing a path for invasion, and enhancing tumor propagation. For further exploration, we developed an interactive online tool at http://www.glioma-microglia.com with all expression data and additional functional and pathway information for each gene

Pulse therapy: Opening new vistas in treatment of pemphigus

Pemphigus is comprised of a group of life-threatening autoimmune diseases that is characterized by circulating IgG antibodies targeting several types of keratinocyte antigens. After introduction of systemic steroids, survival has improved dramatically. However, mortality and morbidity were still very high due to side effects of steroids. Pulse therapy is defined as discontinuous/intermittent intravenous infusion of very high doses of corticosteroids along with certain immunosuppressive agents over a short period. This therapy was introduced to minimize the side effects of conventional corticosteroid therapy. The target is to achieve a faster response and stronger efficacy and to decrease the need for long-term use of systemic corticosteroids. As a result, this therapy has gained its popularity since three decades. The purpose of this article is to review the various available pulse therapy regimens with dosage, indications and contraindications and side effects

Cough-induced Diaphragmatic and Abdominal Hernia in an Asthma Patient – A Case Report

The list of complications of coughing is very long. Chronic cough as in asthma can affect every system in our body such as cardiovascular, gastrointestinal, neurological, musculoskeletal, and diaphragm. We report a case of 46-year-old male patient who was suffering from asthma for the past 15 years with occasional violent coughing. The X-ray of that patient was suggestive of pleural effusion which was misleading. A computed tomography scan of the thorax and the abdomen revealed the presence of diaphragmatic and abdominal hernia. The patient had no other history which can contribute to diaphragmatic injury except chronic cough. We found a chronic uncontrolled cough complicated with diaphragmatic and abdominal wall hernia

Cloning, expression, purification, crystallization and preliminary crystallographic analysis of pseudo death-effector domain of HIPPI, a molecular partner of Huntingtin-interacting protein HIP-1

A pseudo death-effector domain (pDED) of HIPPI, a partner of Huntingtin-interacting protein HIP1, has been cloned, overexpressed and crystallized. The crystals of pDED-HIPPI diffracted to 2.2 Å

Intermediates Involved in the 2e^–/2H⁺ Reduction of CO₂ to CO by Iron(0) Porphyrin

The reduction of CO₂ by an iron porphyrin complex with a hydrogen bonding distal pocket involves at least two intermediates. The resonance Raman data of intermediate I, which could only be stabilized at −95 °C, indicates that it is a Fe­(II)–CO₂^2– adduct and is followed by an another intermediate II at −80 °C where the bound CO₂ in intermediate I is protonated to form a Fe­(II)–COOH species. While the initial protonation can be achieved using weak proton sources like MeOH and PhOH, the facile heterolytic cleavage of the C–OH bond in intermediate II requires strong acids

Activating Fe(I) Porphyrins for the Hydrogen Evolution Reaction Using Second-Sphere Proton Transfer Residues

Iron porphyrin complexes with second-sphere distal triazole residues show a hydrogen evolution reaction (HER) catalyzed by the Fe­(I) state in both organic and aqueous media, whereas an analogous iron porphyrin complex without the distal residues catalyzes the HER in the formal Fe(0) state. This activation of the Fe­(I) state by the second-sphere residues lowers the overpotential of the HER by these iron porphyrin complexes by 50%. Experimental data and theoretical calculations indicate that the distal triazole residues, once protonated, enhance the proton affinity of the iron center via formation of a dihydrogen bond with an Fe­(III)–H^– intermediate