Four-and-a-Half LIM-Domain Protein 2 (FHL2) Induces Neuropeptide Y (NPY) in Macrophages in Visceral Adipose Tissue and Promotes Diet-Induced Obesity.

Obesity is characterized by the expansion of the adipose tissue, usually accompanied by inflammation, with a prominent role of macrophages infiltrating the visceral adipose tissue (VAT). This chronic inflammation is a major driver of obesity-associated comorbidities. Four-and-a-half LIM-domain protein 2 (FHL2) is a multifunctional adaptor protein that is involved in the regulation of various biological functions and the maintenance of the homeostasis of different tissues.

Emergency Free-Hand Bedside Catheter Evacuation of Large Intracerebral Hematomas Following Thrombolysis for Ischemic Stroke: A Case Series.

Introduction: Symptomatic intracerebral hemorrhage (sICH) following systemic thrombolysis for ischemic stroke is often devastating, and open surgical evacuation is considered dangerous due to the increased risk of perioperative bleeding, and stereotactic placement of a catheter is too time-consuming. We therefore evaluated the feasibility of a free-hand bedside catheter technique for emergency hematoma evacuation.

Methods: Patients who had a supratentorial sICH after thrombolysis, a hematoma volume > 30 ml, and an ensuing reduction in vigilance were consecutively treated with acute minimally invasive catheter hematoma evacuation.

The Memorial Sloan Kettering Cancer Center Nomogram is More Accurate than the 2009 FIGO Staging System in the Prediction of Overall Survival in a German Endometrial Cancer Patient Cohort.

Background: Despite the complexity of endometrial cancer (EC) tumor biology, treatment decisions are still mainly based on the post-surgical International Federation of Gynecology and Obstetrics (FIGO) stage. Prediction models considering more prognostic factors may represent a better risk assessment than FIGO stage alone. We tested the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram for the prediction of overall survival (OS) in a German EC population.

The Co-operation of RUNX1 with LDB1, CDK9 and BRD4 Drives Transcription Factor Complex Relocation During Haematopoietic Specification.

Haematopoietic cells arise from endothelial cells within the dorsal aorta of the embryo via a process called the endothelial-haematopoietic transition (EHT). This process crucially depends on the transcription factor RUNX1 which rapidly activates the expression of genes essential for haematopoietic development. Using an inducible version of RUNX1 in a mouse embryonic stem cell differentiation model we showed that prior to the EHT, haematopoietic genes are primed by the binding of the transcription factor FLI1.

Bipolar vessel-sealing devices in laparoscopic hysterectomies: a multicenter randomized controlled clinical trial.

Objective: To compare operating time and blood loss in patients undergoing total laparoscopic hysterectomies (TLH) for benign conditions with either the Marseal™ IQ 5 mm (MS) or the Ligasure™ 5 mm (LS) vessel-sealing device.

Design And Setting: A randomized controlled clinical trial (RCT) in two German gynecology departments.

Patients: 74 patients scheduled to undergo TLH for a symptomatic fibroid uterus, adenomyosis or severe meno-metrorrhagia.

1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) Alters Cell Cycle Progression in Human Neuroblastoma Cell Lines.

1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline, abbreviated as TaClo, is an endogenous neurotoxin capable of formation in the brain through the condensation of neuronal tryptamine with ingested exogenous toxins such as trichloroethylene or chloral hydrate. Due to its structural resemblance to 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), and similar ability to inhibit mitochondrial complex I, TaClo has been implicated in the etiology of Parkinson's disease. Previous studies have shown the cytotoxicity of TaClo in various cell culture models.

Inhibition of neuroinflammation by thymoquinone requires activation of Nrf2/ARE signalling.

Thymoquinone is an antioxidant phytochemical that has been shown to inhibit neuroinflammation. However, little is known about the potential roles of intracellular antioxidant signalling pathways in its anti-inflammatory activity. The objective of this study was to elucidate the roles played by activation of the Nrf2/ARE antioxidant mechanisms in the anti-inflammatory activity of this compound.

CD24+ tumor-initiating cells from oral squamous cell carcinoma induce initial angiogenesis in vivo.

Background: In oral squamous cell carcinoma (OSCC), a minor subset of cancer stem cells has been identified using the surface marker CD24. The CD24+ cell population is involved in initiating, maintaining, and expanding tumor growth, but has not been reported to be involved in angiogenesis to date.

Methods: NOD/SCID mice were equipped with dorsal skinfold chambers and gelatin sponges seeded with CD24+, CD24-, and unsorted cancer cells suspended in Matrigel® were implanted.

Alleviation of Microglial Activation Induced by p38 MAPK/MK2/PGE Axis by Capsaicin: Potential Involvement of other than TRPV1 Mechanism/s.

Exaggerated inflammatory responses in microglia represent one of the major risk factors for various central nervous system's (CNS) associated pathologies. Release of excessive inflammatory mediators such as prostaglandins and cytokines are the hallmark of hyper-activated microglia. Here we have investigated the hitherto unknown effects of capsaicin (cap) - a transient receptor potential vanilloid 1 (TRPV1) agonist- in murine primary microglia, organotypic hippocampal slice cultures (OHSCs) and human primary monocytes.

Neuroprotective effects of intrastriatal injection of rapamycin in a mouse model of excitotoxicity induced by quinolinic acid.

Background: The mammalian target of rapamycin (mTOR) is a kinase involved in a variety of physiological and pathological functions. However, the exact role of mTOR in excitotoxicity is poorly understood. Here, we investigated the effects of mTOR inhibition with rapamycin against neurodegeneration, and motor impairment, as well as inflammatory profile caused by an excitotoxic stimulus.

Antimalarial Drug Artemether Inhibits Neuroinflammation in BV2 Microglia Through Nrf2-Dependent Mechanisms.

Artemether, a lipid-soluble derivative of artemisinin has been reported to possess anti-inflammatory properties. In this study, we have investigated the molecular mechanisms involved in the inhibition of neuroinflammation by the drug. The effects of artemether on neuroinflammation-mediated HT22 neuronal toxicity were also investigated in a BV2 microglia/HT22 neuron co-culture.

Rice bran derivatives alleviate microglia activation: possible involvement of MAPK pathway.

Background: Hyperactivation of microglia is considered to be a key hallmark of brain inflammation and plays a critical role in regulating neuroinflammatory events. Neuroinflammatory responses in microglia represent one of the major risk factors for various neurodegenerative diseases. One of the strategies to protect the brain and slow down the progression of these neurodegenerative diseases is by consuming diet enriched in anti-oxidants and polyphenols.

Randomized Open Trial Comparing 2-Dose Regimens of the Human Papillomavirus 16/18 AS04-Adjuvanted Vaccine in Girls Aged 9-14 Years Versus a 3-Dose Regimen in Women Aged 15-25 Years.

Background: This randomized, open trial compared regimens including 2 doses (2D) of human papillomavirus (HPV) 16/18 AS04-adjuvanted vaccine in girls aged 9-14 years with one including 3 doses (3D) in women aged 15-25 years.

Methods: Girls aged 9-14 years were randomized to receive 2D at months 0 and 6 (M0,6; (n = 550) or months 0 and 12 (M0,12; n = 415), and women aged 15-25 years received 3D at months 0, 1, and 6 (n = 482). End points included noninferiority of HPV-16/18 antibodies by enzyme-linked immunosorbent assay for 2D (M0,6) versus 3D (primary), 2D (M0,12) versus 3D, and 2D (M0,6) versus 2D (M0,12); neutralizing antibodies; cell-mediated immunity; reactogenicity; and safety.

Poly(I:C) increases the expression of mPGES-1 and COX-2 in rat primary microglia.

Background: Microglia recognize pathogen-associated molecular patterns such as double-stranded RNA (dsRNA) present in some viruses. Polyinosinic-polycytidylic acid [poly(I:C)] is a synthetic analog of dsRNA that activates different molecules, such as retinoic acid-inducible gene I, melanoma differentiation-associated gene 5, and toll-like receptor-3 (TLR3). Poly(I:C) increases the expression of different cytokines in various cell types.

Putative CD133+ melanoma cancer stem cells induce initial angiogenesis in vivo.

Tumor angiogenesis is essential for tumor growth and metastasis, and is regulated by a complex network of various types of cells, chemokines, and stimulating factors. In contrast to sprouting angiogenesis, tumor angiogenesis is also influenced by hypoxia, inflammation, and the attraction of bone-marrow-derived cells. Recently, cancer stem cells have been reported to mimic vascularization by differentiating into endothelial cells and inducing vessel formation.

microRNA-26a modulates inflammatory response induced by toll-like receptor 4 stimulation in microglia.

MiRNAs, a family of small non-coding RNAs, have emerged as novel post-transcriptional regulators of numerous cellular responses. Although the involvement of miRNAs in the regulation of neuroinflammation in various neurological diseases has been previously studied, their role in the production of inflammatory mediators during microglia activation is poorly understood. In this study, the role of miR-26a has been investigated in the modulation of inflammatory response in cultured microglia.

Quantifying helper cell function of human TFH cells in vitro.

Blood-circulating CXCR5(+) CD4(+) T cells and T follicular helper (TFH) cells, which participate in germinal center (GC) reactions within secondary lymphoid organs, are specialized in providing help to B cells. This chapter describes ways to isolate TFH-like cells out of peripheral blood or tonsils and to quantify their B cell helper function. This comprises different co-culture approaches of TFH-like cells and B cells and the evaluation of their capacity to induce immunoglobulin secretion and plasma cell differentiation.

PI3Kγ deficiency enhances seizures severity and associated outcomes in a mouse model of convulsions induced by intrahippocampal injection of pilocarpine.

Phosphatidylinositol 3-kinase (PI3K) is an enzyme involved in different pathophysiological processes, including neurological disorders. However, its role in seizures and postictal outcomes is still not fully understood. We investigated the role of PI3Kγ on seizures, production of neurotrophic and inflammatory mediators, expression of a marker for microglia, neuronal death and hippocampal neurogenesis in mice (WT and PI3Kγ(-/-)) subjected to intrahippocampal microinjection of pilocarpine.

Enhanced FHL2 and TGF-β1 Expression Is Associated With Invasive Growth and Poor Survival in Malignant Melanomas.

Objectives: This study examines the expression and the role of four-and-a-half LIM domains protein 2 (FHL2) and transforming growth factor β1 (TGF-β1) in human malignant melanoma. It is determined whether both proteins influence melanoma survival time.

Methods: We analyzed the immunohistochemical staining intensities of FHL2 and TGF-β1 in normal skin and in 50 malignant melanomas with different mutation status (BRAF-V600E, NRAS codon 61 mutation, and wild type).

Tumoral expression of nuclear cofactor FHL2 is associated with lymphatic metastasis in sporadic but not in HNPCC-associated colorectal cancer.

Background: Four and a half LIM domain protein-2 (FHL2) is part of the focal adhesion structures modulating cell motility. FHL2 may translocate into the nucleus serving as a transcriptional cofactor binding several transcription factors. Overexpression of FHL2 has been linked to cancer progression in various neoplasias.

AM404 inhibits NFAT and NF-κB signaling pathways and impairs migration and invasiveness of neuroblastoma cells.

N-Arachidonoylphenolamine (AM404), a paracetamol lipid metabolite, is a modulator of the endocannabinoid system endowed with pleiotropic activities. AM404 is a dual agonist of the Transient Receptor Potential Vanilloid type 1 (TRPV1) and the Cannabinoid Receptor type 1 (CB₁) and inhibits anandamide (AEA) transport and degradation. In addition, it has been shown that AM404 also exerts biological activities through TRPV1- and CB₁ -independent pathways.