Tumor-Derived Prostaglandin E2 Promotes p50 NF-κB-Dependent Differentiation of Monocytic MDSCs.

Myeloid-derived suppressor cells (MDSC) include immature monocytic (M-MDSC) and granulocytic (PMN-MDSC) cells that share the ability to suppress adaptive immunity and to hinder the effectiveness of anticancer treatments. Of note, in response to IFNγ, M-MDSCs release the tumor-promoting and immunosuppressive molecule nitric oxide (NO), whereas macrophages largely express antitumor properties. Investigating these opposing activities, we found that tumor-derived prostaglandin E2 (PGE2) induces nuclear accumulation of p50 NF-κB in M-MDSCs, diverting their response to IFNγ toward NO-mediated immunosuppression and reducing TNFα expression.

Protumor Steering of Cancer Inflammation by p50 NF-κB Enhances Colorectal Cancer Progression.

Although tumor-associated macrophages (TAM) display a M2-skewed tumor-promoting phenotype in most cancers, in colorectal cancer, both TAM polarization and its impact remain controversial. We investigated the role of the M2-polarizing p50 NF-κB subunit in orchestrating TAM phenotype, tumor microenvironment composition, and colorectal cancer progression. We first demonstrated, by parallel studies in colitis-associated cancer (CAC) and in genetically driven Apc mouse models, that the p50-dependent inhibition of M1-polarized gut inflammation supported colorectal cancer development.

Uncontrolled IL-17 Production by Intraepithelial Lymphocytes in a Case of non-IPEX Autoimmune Enteropathy.

Objectives: To provide a functional and phenotypic characterization of immune cells infiltrating small intestinal mucosa during non-IPEX autoimmune enteropathy (AIE), as to gain insights on the pathogenesis of this clinical condition.

Methods: Duodenal biopsies from a patient with AIE at baseline and following drug-induced remission were analyzed by immunohistochemistry, immunofluorescence, and flow cytometry, and results were compared with those obtained from patients with active celiac disease, ileal Crohn's disease and healthy controls. Lamina propria (LP) and intraepithelial (IELs) lymphocytes from AIE and controls were analyzed for mechanisms regulating cytokine production.

Vascular pentraxin 3 controls arterial thrombosis by targeting collagen and fibrinogen induced platelets aggregation.

Aim: The long pentraxin PTX3 plays a non-redundant role during acute myocardial infarction, atherosclerosis and in the orchestration of tissue repair and remodeling during vascular injury, clotting and fibrin deposition. The aim of this work is to investigate the molecular mechanisms underlying the protective role of PTX3 during arterial thrombosis.

Methods And Results: PTX3 KO mice transplanted with bone marrow from WT or PTX3 KO mice presented a significant reduction in carotid artery blood flow following FeCl3 induced arterial thrombosis (-80.

Occurrence and significance of tumor-associated neutrophils in patients with colorectal cancer.

Inflammatory cells are an essential component of the tumor microenvironment. Neutrophils have emerged as important players in the orchestration and effector phase of innate and adaptive immunity. The significance of tumor-associated neutrophils (TAN) in colorectal cancer (CRC) has been the subject of conflicting reports and the present study was designed to set up a reliable methodology to assess TAN infiltration in CRC and to evaluate their clinical significance.

RORC1 Regulates Tumor-Promoting "Emergency" Granulo-Monocytopoiesis.

Cancer-driven granulo-monocytopoiesis stimulates expansion of tumor promoting myeloid populations, mostly myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). We identified subsets of MDSCs and TAMs based on the expression of retinoic-acid-related orphan receptor (RORC1/RORγ) in human and mouse tumor bearers. RORC1 orchestrates myelopoiesis by suppressing negative (Socs3 and Bcl3) and promoting positive (C/EBPβ) regulators of granulopoiesis, as well as the key transcriptional mediators of myeloid progenitor commitment and differentiation to the monocytic/macrophage lineage (IRF8 and PU.

An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode.

Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key component of the humoral arm of innate immunity. In four different models of tissue damage in mice, PTX3 deficiency was associated with increased fibrin deposition and persistence, and thicker clots, followed by increased collagen deposition, when compared with controls. Ptx3-deficient macrophages showed defective pericellular fibrinolysis in vitro.

PTX3 is an extrinsic oncosuppressor regulating complement-dependent inflammation in cancer.

PTX3 is an essential component of the humoral arm of innate immunity, playing a nonredundant role in resistance against selected microbes and in the regulation of inflammation. PTX3 activates and regulates the Complement cascade by interacting with C1q and with Factor H. PTX3 deficiency was associated with increased susceptibility to mesenchymal and epithelial carcinogenesis.

The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection.

Immunity in the urinary tract has distinct and poorly understood pathophysiological characteristics and urinary tract infections (UTIs) are important causes of morbidity and mortality. We investigated the role of the soluble pattern recognition molecule pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity, in UTIs. PTX3-deficient mice showed defective control of UTIs and exacerbated inflammation.

Hind limb muscle atrophy precedes cerebral neuronal degeneration in G93A-SOD1 mouse model of amyotrophic lateral sclerosis: a longitudinal MRI study.

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disorder caused by the degeneration of motor neurons in the CNS, which results in complete paralysis of skeletal muscles. Recent experimental studies have suggested that the disease could initiate in skeletal muscle, rather than in the motor neurons. To establish the timeframe of motor neuron degeneration in relation to muscle atrophy in motor neuron disease, we have used MRI to monitor changes throughout disease in brain and skeletal muscle of G93A-SOD1 mice, a purported model of ALS.

Glutamate and glutathione interplay in a motor neuronal model of amyotrophic lateral sclerosis reveals altered energy metabolism.

Impairment of mitochondrial function might contribute to oxidative stress associated with neurodegeneration in amyotrophic lateral sclerosis (ALS). Glutamate levels in tissues of ALS patients are sometimes altered. In neurons, mitochondrial metabolism of exogenous glutamine is mainly responsible for the net synthesis of glutamate, which is a neurotransmitter, but it is also necessary for the synthesis of glutathione, the main endogenous antioxidant.

High-resolution MRI of carotid plaque with a neurovascular coil and contrast-enhanced MR angiography: one-stop shopping for the comprehensive assessment of carotid atherosclerosis.

Objective: The objective of our study was to assess a protocol of study of carotid atherosclerosis coupling vascular wall imaging and luminal imaging in the same examination and to evaluate the accuracy of high-resolution MRI with a neurovascular coil in carotid plaque characterization.

Subjects And Methods: Thirty-two consecutive patients with 34 carotid artery stenoses were prospectively enrolled. MRI was performed on a 1.

[Our experience in the chemical spinal neuromodulation in chronic pain from spinal collapse due to osteoporosis.].

Aims: Osteoporosis is a metabolic disease of the bone characterized by reduced bone mass and microstructural deterioration of bone tissue with a consequent increase in bone fragility and risk of vertebral collapse. Treatment of osteoporosis with the new molecule is effective in improving the density and quality of bone but does not provide an analgesic effect for patients with vertebral collapse. The treatment of chronic pain from vertebral collapse is difficult and may require the use of opioids, but for some patients the intake of these drugs is burdened with systemic side effects.

Low-dose unenhanced CT protocols according to individual body size for evaluating suspected renal colic: cumulative radiation exposures.

Purpose: The aim of this study was to assess the radiation dose of dose-reduced unenhanced abdominal multidetector computed tomography (MDCT) scan protocols for suspected renal colic in patients within normal weight range and overweight-obese patients and to record the cumulative dose of repeated examinations.

Materials And Methods: Over a 2-year period, we performed 1,026 unenhanced CT examinations for urolithiasis; among these, 675 were performed on 636 patients referred from the emergency department. Patients were divided into two groups on the basis of body mass index (BMI): normal weight (BMI <25 kg/m(2) group 1); overweight and obese (BMI >25 kg/m(2) group 2).

[The chemical neuromodulation of pain: a review].

The chronic pain is a true emergency. In fact, the study "Pain in Europe 2005" showed that 26% of the Italian population is suffering by it. Chronic pain can be benign, when caused by a tissular damage, or malignant when cancer-related.

Characterization of detergent-insoluble proteins in ALS indicates a causal link between nitrative stress and aggregation in pathogenesis.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease, and protein aggregation has been proposed as a possible pathogenetic mechanism. However, the aggregate protein constituents are poorly characterized so knowledge on the role of aggregation in pathogenesis is limited.

Methodology/principal Findings: We carried out a proteomic analysis of the protein composition of the insoluble fraction, as a model of protein aggregates, from familial ALS (fALS) mouse model at different disease stages.

[Cervical lymphoadenopathy due to Pseudomonas aeruginosa following mesotherapy].

Mesotherapy is a treatment method devised for controlling several diseases by means of subcutaneous microinjections given at or around the affected areas at short time intervals. It is used to treat a variety of medical conditions, amongst which all orthopaedic diseases and rheumatic pain. Mesotherapy is especially indicated for neck pain.

Adaptation to G93Asuperoxide dismutase 1 in a motor neuron cell line model of amyotrophic lateral sclerosis: the role of glutathione.

Motor neuron degeneration in amyotrophic lateral sclerosis involves oxidative damage. Glutathione (GSH) is critical as an antioxidant and a redox modulator. We used a motor neuronal cell line (NSC-34) to investigate whether wild-type and familial amyotrophic lateral sclerosis-linked G93A mutant Cu,Zn superoxide dismutase (wt/G93ASOD1) modified the GSH pool and glutamate cysteine ligase (GCL), the rate-limiting enzyme for GSH synthesis.

[Cannabinoids in the control of pain].

Hemp (Cannabis sativa L.) has been used since remotes ages as a herbal remedy. Only recently the medical community highlighted the pharmacological scientific bases of its effects.

Subintimal angioplasty as the first-choice revascularization technique for infrainguinal arterial occlusions in patients with critical limb ischemia.

Our aim was to appraise the feasibility and outcomes of subintimal angioplasty (SA) for the percutaneous revascularization of infrainguinal arterial occlusions in patients with critical limb ischemia (CLI). We retrospectively assessed 117 SA procedures in 109 limbs with complete infrainguinal occlusions from 105 patients with CLI. Among these, the superficial femoral artery (SFA) was the only occluded vessel in 27 limbs, while infrapopliteal (IP) occlusions occurred in 82.

Auricular acupuncture to resolve the exacerbations in ocular myasthenia--a case report.

Ocular myasthenia is a neuromuscular autoimmune disorder in which the clinical symptoms are restricted to the external ocular muscles with either ptosis or diplopia, or both. The condition may follow a relapsing and remitting course. Conventional therapy consists of anticholinergic drugs, corticosteroids and immunosuppressants.

Short term analgesia based sedation in the Intensive Care Unit: morphine vs remifentanil + morphine.

Aim: The aim of the study was the evaluation of postoperative short term analgesia-based sedation provided by a continuous i.v. morphine vs morphine+remifentanil infusion in the ICU.