Muscle expression of a local Igf-1 isoform protects motor neurons in an ALS mouse model

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by a selective degeneration of motor neurons, atrophy, and paralysis of skeletal muscle. Although a significant proportion of familial ALS results from a toxic gain of function associated with dominant SOD1 mutations, the etiology of the disease and its specific cellular origins have remained difficult to define. Here, we show that muscle-restricted expression of a localized insulin-like growth factor (Igf) -1 isoform maintained muscle integrity and enhanced satellite cell activity in SOD1G93A transgenic mice, inducing calcineurin-mediated regenerative pathways. Muscle-specific expression of local Igf-1 (mIgf-1) isoform also stabilized neuromuscular junctions, reduced inflammation in the spinal cord, and enhanced motor neuronal survival in SOD1G93A mice, delaying the onset and progression of the disease. These studies establish skeletal muscle as a primary target for the dominant action of inherited SOD1 mutation and suggest that muscle fibers provide appropriate factors, such as mIgf-1, for neuron survival

Ionically conducting and photoresponsive liquid crystalline terpolymers : towards multifunctional polymer electrolytes

ARG and AMF thank the financial support of the Generalitat Valenciana, through the Grisolia and Forteza programs, and the Spanish Ministry of Science and Innovation, through the Research Projects ENE2007-67584-C03 and UPOVCE-3E-013 and the awarding of two FPI and FPU pre-doctoral grants. AMF and NFKA would like to thank the Royal Academy of Engineering for the award of the Newton Research Collaboration Programme grant NRCP1516/4/61. AMF acknowledges the School of Engineering of the University of Aberdeen for financial support.Peer reviewedPostprin

Phase II study of epirubicin, oxaliplatin and docetaxel combination in metastatic gastric or gastroesophageal junction adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>This phase II study was designed to evaluate the activity and safety of a combination of epirubicin, oxaliplatin and docetaxel in metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.</p> <p>Methods</p> <p>Forty patients with measurable distant metastases received epirubicin 50 mg/m², docetaxel 60 mg/m²followed by oxaliplatin 100 mg/m²on day 1 of each 21-day cycle. Primary end point was response rates (RR).</p> <p>Results</p> <p>All patients were evaluable. The overall RR was 47.5% (95% confidence interval (CI) 32–63). The disease control was 80%. Median time for response was 6 weeks. Median time to progression was 6.3 months (95% CI 5.4–7.2) and the median overall survival time was 12.1 months (95% CI 10.7–13.5). Grade 3/4 neutropenia occurred in 50% of patients with two episodes of febrile neutropenia (5%). Other non-hematological grade 3 toxicities included sensory neuropathy in two patiens (5%), vomiting and mucositis in two patients (5%) and diarrhea in one patient (2.5%).</p> <p>Conclusion</p> <p>The combination of epirubicin, oxaliplatin and docetaxel was found to be effective and well tolerated in patiens with metastatic gastric or GEJ adenocarcinoma and maybe an appropriate regimen to be used in the neoadjuvant setting and with molecularly targeted agents.</p

Muscle Involvement and IGF-1 Signaling in Genetic Disorders: New Therapeutic Approaches

In the last decade, dramatic progress has been made in elucidating the molecular defects underlying a number of muscle diseases. With the characterization of mutations responsible for muscle dysfunction in several inherited pathologies, and the identification of novel signaling pathways, subtle alterations in which can lead to significant defects in muscle metabolism, the field is poised to devise successful strategies for treatment of this debilitating and often fatal group of human ailments. Yet progress has been slow in therapeutic applications of our newly gained knowledge. The complexity of muscle types, the intimate relationship between structural integrity and mechanical function, and the sensitivity of skeletal muscle to metabolic perturbations have impeded rapid progress in successful clinical intervention. The relatively poor regenerative properties of striated muscle compound the devastating effects of muscle degeneration. Perhaps the most difficult hurdle is the sheer volume of tissue that must be treated to effect a significant improvement in quality of life. Recent studies on the role of insulin-like growth factor-1 in skeletal muscle growth and homeostasis have excited new interest in this important mediator of anabolic pathways and suggest promising new avenues for intervention in catabolic disease. In this review, we will discuss the potential therapeutic role of local insulin-like growth factor 1 in the treatment of muscle wasting associated with muscle diseases. Copyright (C) 2009 S. Karger AG, Base

Effect of humidity and nanocellulose content on Polyvinylamine-nanocellulose hybrid membranes for CO2capture

In order to address the need for more efficient technologies for carbon capture applications, a novel type of nanocellulose based hybrid membrane has been successfully prepared by blending the commercial Polyvinylamine solution Lupamin\uc2\uae 9095 (BASF) with Nano Fibrillated Cellulose (NFC) to improve its mechanical and separation capabilities. Self-standing films with different nanocellulose loading (from 30 to 70 wt%) have been prepared and characterized at 35 \uc2\ub0C through water vapor sorption experiments and humid gas permeation tests. As expected, membrane permeability consistently increased with increasing water vapor and a higher presence of Lupamin in the film resulted in an increment of both gas permeability and selectivity. In particular blends with a NFC content of 70 wt% Lupamin reached an ideal selectivity of 135 for the separation of CO2/CH4and 218 for CO2/N2, at 60 RH%, while the maximum permeability in the order of 187 Barrer was instead reached at 80% RH. Water vapor solubility was also measured and modeled through Park Model to correlate the gas separation properties with the effective content of water present in the membrane matrix. As expected, a higher content of the hydrophilic polymer resulted in a larger water uptake, which at medium to high humidity appeared to trigger a water clustering phenomenon in the matrix. This fact was accompanied by a substantial relaxation of the polymer network, causing a marked reduction of selectivity, which dropped, at the highest RH investigated, to values in the order of 30 and 80 towards CH4and N2respectively. Despite this loss in performance, most materials tested still showed very interesting properties, well above Robeson's 2008 Upper Bound, making them an interesting alternative for traditional gas separation processes

The role of Igf-1 on Muscle Wasting: a Therapeutic Approach

While much has been learned about skeletal muscle formation in the embryo, less is known about the molecular pathways controlling skeletal myocyte survival and plasticity in the adult. Tissue remodelling is an important physiological process which allows skeletal muscle to respond to environmental demands. In particular, the complex contractile properties of skeletal muscle depend upon a heterogeneous population of myofibers that confer the functional plasticity necessary to modulate responses to a wide range of external factors, including physical activity, change in hormone levels and motor-neuron activity, oxygen and nutrients supply. Fiber type is an essential determinant of muscle function and alteration in fiber composition represents a major component in muscle wasting associated with muscle diseases. In this context, the prolongation of skeletal muscle strength in aging and neuromuscular disease has been the objective of numerous studies employing a variety of approaches. To date however, efforts to prevent or attenuate age- or disease-related muscle degeneration have been largely unsuccessful. In this context, where direct therapeutic approaches to redress the primary disease are still sub-optimal, it may be more effective to focus on strategies for improving skeletal muscle function. In this review we will discuss the potential therapeutic role of Insulin-like Growth Factor 1 (IGF-1) in treatment of muscle wasting associated with several muscle diseases

A Multifactorial Regulation of Glutathione Metabolism behind Salt Tolerance in Rice

Knowledge of the stress-induced metabolic alterations in tolerant and sensitive plants is pivotal for identifying interesting traits that improve plant resilience toward unfavorable environmental conditions. This represents a hot topic area of plant science, particularly for crops, due to its implication in food security. Two rice varieties showing dissimilar resistance to salt, Baldo and Vialone Nano, have been studied to investigate the mechanisms underpinning tolerance toward salinity, and these studies have focused on the root system. A detailed analysis of the salt stress-dependent modulation of the redox network is here presented. The different phenotype observed after salt exposure in the two rice varieties is coherent with a differential regulation of cell-cycle progression and cell-death patterns observed at root level. Baldo, the tolerant variety, already showed a highly responsive antioxidative capacity in control conditions. Consistently, stressed Baldo plants showed a different pattern of H2O2 accumulation compared to Vialone Nano. Moreover, glutathione metabolism was finely modulated at transcriptional, post-transcriptional, and post-translational levels in Baldo. These results contribute to highlight the role of ROS and antioxidative pathways as a part of a complex redox network activated in rice toward salt stress

Green in situ synthesis of Ag nanoparticles-peptide hydrogel composites: investigation of their antibacterial activities

Among biomaterials, peptide hydrogels attract many attentions. They are biocompatible, biodegradable, and due to the liquid form of their precursors at room temperature, they are injectable. These features make them good candidates for developing biomedical applications [1]. The aim of this research is to synthesize peptide-based hydrogels and impregnate them with silver nanoparticles to have the resultant hydrogel/nanoparticles hybrid. The amino acid, fluorenylmethyloxycarbonyl phenyl alanine (Fmoc-Phe) and diphenylalanine (Phe2) are used for the hydrogel synthesis [2]. Green chemical methods have been applied for the synthesis of hydrogel and nanoparticles. Regarding the biological applications, the hydrogel/nanoparticles hybrid can be used in the field of antibacterial materials. Structure, mechanical stability and morphology of this nanohybrid were characterized with different techniques such as FESEM, FTIR, UV-Vis, SAXS, ICP, Rheology measurement, and XPS [3]