HuR modulation counteracts lipopolysaccharide response in murine macrophages.

Lipopolysaccharide (LPS) exposure to macrophages induces an inflammatory response, which is regulated at the transcriptional and post-transcriptional levels. HuR (ELAVL1) is an RNA-binding protein that regulates cytokines and chemokines transcripts containing AU/U-rich elements (AREs) and mediates the LPS-induced response. Here, we show that small-molecule tanshinone mimics (TMs) inhibiting HuR-RNA interaction counteract LPS stimulus in macrophages.

Hydrochar and hydrochar co-compost from OFMSW digestate for soil application: 3. Toxicological evaluation.

Modern societies produce ever-increasing amounts of waste, e.g. organic fraction of municipal solid waste (OFMSW).

Large-Scale Validation of the Paddling Pool Task in the Clockmaze for Studying Hippocampus-Based Spatial Cognition in Mice.

Rationally designed behavioral tests are important tools to assess the function of specific brain regions. The hippocampus is a crucial neural substrate for spatial cognition, and many studies have linked hippocampal dysfunction with defects on spatial learning and memory in neurological conditions ranging from Alzheimer's disease to autoimmune syndromes, such as neuropsychiatric lupus. While our understanding of hippocampal function, from the molecular to the system levels, has increased dramatically over the last decades, this effort has not yet translated into efficacious therapies for cognitive impairment.

Aberrant Somatosensory Processing and Connectivity in Mice Lacking .

Overreactivity and defensive behaviors in response to tactile stimuli are common symptoms in autism spectrum disorder (ASD) patients. Similarly, somatosensory hypersensitivity has also been described in mice lacking ASD-associated genes such as (fragile X mental retardation protein 1). knock-out mice also show reduced functional connectivity between sensory cortical areas, which may represent an endogenous biomarker for their hypersensitivity.

Standardization of methods to record Vagus nerve activity in mice.

Background: The vagus nerve plays an important role in the regulation of organ function, including reflex pathways that regulate immunity and inflammation. Recent studies using genetically modified mice have improved our understanding of molecular mechanisms in the neural control of immunity. However, mapping neural signals transmitted in the vagus nerve in mice has been limited by technical challenges.

Preclinical models of overwhelming sepsis implicate the neural system that encodes contextual fear memory.

Long-term sepsis survivors sustain cryptic brain injury that leads to cognitive impairment, emotional imbalance, and increased disability burden. Suitable animal models of sepsis, such as cecal ligation and puncture (CLP), have permitted the analysis of abnormal brain circuits that underlie post-septic behavioral phenotypes. For instance, we have previously shown that CLP-exposed mice exhibit impaired spatial memory together with depleted dendritic arbors and decreased spines in the apical dendrites of pyramidal neurons in the CA1 region of the hippocampus.

Cytokine-specific Neurograms in the Sensory Vagus Nerve.

The axons of the sensory, or afferent, vagus nerve transmit action potentials to the central nervous system in response to changes in the body's metabolic and physiological status. Recent advances in identifying neural circuits that regulate immune responses to infection, inflammation and injury have revealed that vagus nerve signals regulate the release of cytokines and other factors produced by macrophages. Here we record compound action potentials in the cervical vagus nerve of adult mice and reveal the specific activity that occurs following administration of the proinflammatory cytokines tumor necrosis factor (TNF) and interleukin 1β (IL-1β).

Dynamic NMDAR-mediated properties of place cells during the object place memory task.

N-methyl-D-aspartate receptors (NMDAR) in the hippocampus participate in encoding and recalling the location of objects in the environment, but the ensemble mechanisms by which NMDARs mediate these processes have not been completely elucidated. To address this issue, we examined the firing patterns of place cells in the dorsal CA1 area of the hippocampus of mice (n = 7) that performed an object place memory (OPM) task, consisting of familiarization (T1), sample (T2), and choice (T3) trials, after systemic injection of 3-[(±)2-carboxypiperazin-4yl]propyl-1-phosphate (CPP), a specific NMDAR antagonist. Place cell properties under CPP (CPP-PCs) were compared to those after control saline injection (SAL-PCs) in the same mice.

Construction of microdrive arrays for chronic neural recordings in awake behaving mice.

State-of-the-art electrophysiological recordings from the brains of freely behaving animals allow researchers to simultaneously examine local field potentials (LFPs) from populations of neurons and action potentials from individual cells, as the animal engages in experimentally relevant tasks. Chronically implanted microdrives allow for brain recordings to last over periods of several weeks. Miniaturized drives and lightweight components allow for these long-term recordings to occur in small mammals, such as mice.

HMGB1 mediates cognitive impairment in sepsis survivors.

Severe sepsis, a syndrome that complicates infection and injury, affects 750,000 annually in the United States. The acute mortality rate is approximately 30%, but, strikingly, sepsis survivors have a significant disability burden: up to 25% of survivors are cognitively and physically impaired. To investigate the mechanisms underlying persistent cognitive impairment in sepsis survivors, here we developed a murine model of severe sepsis survivors following cecal ligation and puncture (CLP) to study cognitive impairments.

Prognostic impact of education level of patients with advanced non-small cell lung cancer enrolled in clinical trials.

Background: Socioeconomic status can potentially affect prognosis of cancer patients. Our aim was to describe potential differences in demographic and clinical characteristics, treatment, and survival by education level in patients with advanced non-small cell lung cancer (NSCLC) enrolled in clinical trials of first-line treatment.

Methods: Individual data of Italian patients with advanced NSCLC (stage IV, or IIIB with supraclavicular nodes or malignant pleural effusion), ECOG performance status (PS) 0-2, enrolled in four phase III randomized trials conducted between 1996 and 2005 were pooled.

Cisplatin plus gemcitabine or vinorelbine for elderly patients with advanced non small-cell lung cancer: the MILES-2P studies.

Purpose: Two phase I/II trials were done to evaluate the feasibility of cisplatin combined with gemcitabine or vinorelbine in elderly patients with advanced non-small-cell lung cancer (NSCLC).

Patients And Methods: Patients with advanced NSCLC who were older than 70 years of age and who had a performance status of 0 to 1 were eligible. Cisplatin was given on day 1 (a starting dose of 50 mg/m2 with increasing increments of 10 mg/m2 at each level) and gemcitabine (1,000 mg/m2) or vinorelbine (25 mg/m2) on days 1 and 8.

Pretreatment quality of life and functional status assessment significantly predict survival of elderly patients with advanced non-small-cell lung cancer receiving chemotherapy: a prognostic analysis of the multicenter Italian lung cancer in the elderly study.

Purpose: To study the prognostic value for overall survival of baseline assessment of functional status, comorbidity, and quality of life (QoL) in elderly patients with advanced non-small-cell lung cancer treated with chemotherapy.

Patients And Methods: Data from 566 patients enrolled onto the phase III randomized Multicenter Italian Lung Cancer in the Elderly Study (MILES) study were analyzed. Functional status was measured as activities of daily living (ADL) and instrumental ADL (IADL).

Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer: a pooled analysis of three randomised trials.

Background: Chemotherapy is the standard treatment for advanced non-small-cell lung cancer, and myelosuppression is a common side-effect. We aimed to assess whether haematological toxic effects could be a biological measure of drug activity and a marker of efficacy.

Methods: We analysed data for 1265 patients who received chemotherapy (vinorelbine, gemcitabine, gemcitabine and vinorelbine, cisplatin and vinorelbine, or cisplatin and gemcitabine) within three randomised trials.

Supportive care in patients with advanced non-small-cell lung cancer.

The present study describes supportive care (SC) in patients with advanced non-small-cell lung cancer (NSCLC), evaluating whether it is affected by concomitant chemotherapy, patient's performance status (PS) and age. Data of patients enrolled in three randomised trials of first-line chemotherapy, conducted between 1996 and 2001, were pooled. The analysis was limited to the first three cycles of treatment.

Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group.

Purpose: Platinum-containing chemotherapy regimens are the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), although toxicity is common and may significantly affect the patient's quality of life (QoL). This trial aimed to assess whether a combination of gemcitabine and vinorelbine had benefits in terms of QoL, without influencing negatively on survival, compared with cisplatin-containing regimens.

Patients And Methods: Patients with stage IIIB (effusion and supraclavicular nodes) or IV documented NSCLC who were younger than 70 years of age were randomly assigned gemcitabine plus vinorelbine (GemVin) or either gemcitabine plus cisplatin or vinorelbine plus cisplatin (cisplatin-based).

Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial.

Background: Vinorelbine prolongs survival and improves quality of life in elderly patients with advanced non-small-cell lung cancer (NSCLC). Some studies have also suggested that gemcitabine is well tolerated and effective in such patients. We compared the effectiveness and toxicity of the combination of vinorelbine plus gemcitabine with those of each drug given alone in an open-label, randomized phase III trial in elderly patients with advanced NSCLC.