In-water synthesis of isocyanides under micellar conditions

An in-water dehydration of N-formamides to afford isocyanides using micellar conditions at room temperature is reported. This method allows for the preparation of aliphatic isocyanides in an environmental friendly manner. The replacement of undesirable components such as phosphorous oxychloride, triethyl amine and dichloromethane (the classical combination used for the dehydration of N-formamides), by p-toluen sulphonyl chloride, sodium hydrogen carbonate and water makes this transformation really sustainable and safe

Development of novel antibacterial active, HaCaT biocompatible and biodegradable CA-g-P(3HB)-EC biocomposites with caffeic acid as a functional entity

International audienceWe have developed novel composites by grafting caffeic acid (CA) onto the P(3HB)-EC based material and laccase from Trametes versicolor was used for grafting purposes. The resulting composites were designated as CA-g-P(3HB)EC i.e., P(3HB)-EC (control), 5CA-g-P(3HB)-EC, 10CA-g-P(3HB)-EC, 15CA-g-P(3HB)-EC and 20CA-g-P(3HB)-EC. FT-IR (Fourier-transform infrared spectroscopy) was used to examine the functional and elemental groups of the control and laccase-assisted graft composites. Evidently, 15CA-g-P(3HB)-EC composite exhibited resilient antibacterial activity against Gram-positive and Gram-negative bacterial strains. Moreover, a significant level of biocompatibility and biodegradability of the CA-g-P(3HB)-EC composites was also achieved with the human keratinocytes-like HaCaT cells and soil burial evaluation, respectively. In conclusion, the newly developed novel composites with multi characteristics could well represent the new wave of biomaterials for medical applications, and more specifically have promising future in the infection free would dressings, burn and/or skin regeneration field due to their sophisticated characteristics

Soil and water bioengineering: practice and research needs for reconciling natural hazard control and ecological restoration

Soil and water bioengineering is a technology that encourages scientists and practitioners to combine their knowledge and skills in the management of ecosystems with a common goal to maximize benefits to both man and the natural environment. It involves techniques that use plants as living building materials, for: (i) natural hazard control (e.g., soil erosion, torrential floods and landslides) and (ii) ecological restoration or nature-based re-introduction of species on degraded lands, river embankments, and disturbed environments. For a bioengineering project to be successful, engineers are required to highlight all the potential benefits and ecosystem services by documenting the technical, ecological, economic and social values. The novel approaches used by bioengineers raise questions for researchers and necessitate innovation from practitioners to design bioengineering concepts and techniques. Our objective in this paper, therefore, is to highlight the practice and research needs in soil and water bioengineering for reconciling natural hazard control and ecological restoration. Firstly, we review the definition and development of bioengineering technology, while stressing issues concerning the design, implementation, and monitoring of bioengineering actions. Secondly, we highlight the need to reconcile natural hazard control and ecological restoration by posing novel practice and research questions

Inhalation of the prodrug PI3K inhibitor CL27c improves lung function in asthma and fibrosis

PI3K activation plays a central role in the development of pulmonary inflammation and tissue remodeling. PI3K inhibitors may thus offer an improved therapeutic opportunity to treat non-resolving lung inflammation but their action is limited by unwanted on-target systemic toxicity. Here we present CL27c, a prodrug pan-PI3K inhibitor designed for local therapy, and investigate whether inhaled CL27c is effective in asthma and pulmonary fibrosis. Mice inhaling CL27c show reduced insulin-evoked Akt phosphorylation in lungs, but no change in other tissues and no increase in blood glycaemia, in line with a local action. In murine models of acute or glucocorticoid-resistant neutrophilic asthma, inhaled CL27c reduces inflammation and improves lung function. Finally, inhaled CL27c administered in a therapeutic setting protects from bleomycin-induced lung fibrosis, ultimately leading to significantly improved survival. Therefore, local delivery of a pan-PI3K inhibitor prodrug reduces systemic on-target side effects but effectively treats asthma and irreversible pulmonary fibrosis

Design, Synthesis, Biological Evaluation, and Structure–Activity Relationships of Substituted Phenyl 4-(2-Oxoimidazolidin-1-yl)benzenesulfonates as New Tubulin Inhibitors Mimicking Combretastatin A-4

International audienc

Influence of soil and climate on root zone storage capacity

Root zone storage capacity (Sr) is an important variable for hydrology and climate studies, as it strongly influences the hydrological functioning of a catchment and, via evaporation, the local climate. Despite its importance, it remains difficult to obtain a wellâ founded catchment representative estimate. This study tests the hypothesis that vegetation adapts its Sr to create a buffer large enough to sustain the plant during drought conditions of a certain critical strength (with a certain probability of exceedance). Following this method, Sr can be estimated from precipitation and evaporative demand data. The results of this â climateâ based methodâ are compared with traditional estimates from soil data for 32 catchments in New Zealand. The results show that the differences between catchments in climateâ derived catchment representative Sr values are larger than for soilâ derived Sr values. Using a model experiment, we show that the climateâ derived Sr can better reproduce hydrological regime signatures for humid catchments; for more arid catchments, the soil and climate methods perform similarly. This makes the climateâ based Sr a valuable addition for increasing hydrological understanding and reducing hydrological model uncertainty.Key Points:Plants develop their root systems to survive droughtsModel root zone storage capacity (Sr) can be inferred from climate recordsModel experiment shows that Sr is stronger influenced by climate than by soilPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137190/1/wrcr21890.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137190/2/wrcr21890_am.pd

Non-adenine based purines accelerate wound healing

Wound healing is a complex sequence of cellular and molecular processes that involves multiple cell types and biochemical mediators. Several growth factors have been identified that regulate tissue repair, including the neurotrophin nerve growth factor (NGF). As non-adenine based purines (NABPs) are known to promote cell proliferation and the release of growth factors, we investigated whether NABPs had an effect on wound healing. Full-thickness, excisional wound healing in healthy BALB/c mice was significantly accelerated by daily topical application of NABPs such as guanosine (50% closure by days 2.5′.8). Co-treatment of wounds with guanosine plus anti-NGF reversed the guanosine-promoted acceleration of wound healing, indicating that this effect of guanosine is mediated, at least in part, by NGF. Selective inhibitors of the NGF-inducible serine/threonine protein kinase (protein kinase N), such as 6-methylmercaptopurine riboside abolished the acceleration of wound healing caused by guanosine, confirming that activation of this enzyme is required for this effect of guanosine. Treatment of genetically diabetic BKS.Cg-m+/+lepr db mice, which display impaired wound healing, with guanosine led to accelerated healing of skin wounds (25% closure by days 2.8′.0). These results provide further confirmation that the NABP-mediated acceleration of cutaneous wound healing is mediated via an NGF-dependent mechanism. Thus, NABPs may offer an alternative and viable approach for the treatment of wounds in a clinical setting

The NAMPT inhibitor FK866 reverts the damage in spinal cord injury

<p>Abstract</p> <p>Background</p> <p>Emerging data implicate nicotinamide phosphoribosyl transferase (NAMPT) in the pathogenesis of cancer and inflammation. NAMPT inhibitors have proven beneficial in inflammatory animal models of arthritis and endotoxic shock as well as in autoimmune encephalitis. Given the role of inflammatory responses in spinal cord injury (SCI), the effect of NAMPT inhibitors was examined in this setting.</p> <p>Methods</p> <p>We investigated the effects of the NAMPT inhibitor FK866 in an experimental compression model of SCI.</p> <p>Results</p> <p>Twenty-four hr following induction of SCI, a significant functional deficit accompanied widespread edema, demyelination, neuron loss and a substantial increase in TNF-α, IL-1β, PAR, NAMPT, Bax, MPO activity, NF-κB activation, astrogliosis and microglial activation was observed. Meanwhile, the expression of neurotrophins BDNF, GDNF, NT3 and anti-apoptotic Bcl-2 decreased significantly. Treatment with FK866 (10 mg/kg), the best known and characterized NAMPT inhibitor, at 1 h and 6 h after SCI rescued motor function, preserved perilesional gray and white matter, restored anti-apoptotic and neurotrophic factors, prevented the activation of neutrophils, microglia and astrocytes and inhibited the elevation of NAMPT, PAR, TNF-α, IL-1β, Bax expression and NF-κB activity.</p> <p>We show for the first time that FK866, a specific inhibitor of NAMPT, administered after SCI, is capable of reducing the secondary inflammatory injury and partly reduce permanent damage. We also show that NAMPT protein levels are increased upon SCI in the perilesional area which can be corrected by administration of FK866.</p> <p>Conclusions</p> <p>Our findings suggest that the inflammatory component associated to SCI is the primary target of these inhibitors.</p

A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency.

PURPOSE: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles. METHODS: We performed a prospective observational 12-month multicenter study in France via the CEREDIH network of regional PID reference centers from November 2010 to October 2011. All patients with PIDs requiring emergency hospital admission were included. RESULTS: A total of 200 admissions concerned 137 patients (73 adults and 64 children, 53% of whom had antibody deficiencies). Thirty admissions were reported for 16 hematopoietic stem cell transplantation recipients. When considering the 170 admissions of non-transplant patients, 149 (85%) were related to acute infections (respiratory tract infections and gastrointestinal tract infections in 72 (36%) and 34 (17%) of cases, respectively). Seventy-seven percent of the admissions occurred during winter or spring (December to May). The in-hospital mortality rate was 8.8% (12 patients); death was related to a severe infection in 11 cases (8%) and Epstein-Barr virus-induced lymphoma in 1 case. Patients with a central venous catheter (n = 19, 13.9%) were significantly more hospitalized for an infection (94.7%) than for a non-infectious reason (5.3%) (p = 0.04). CONCLUSION: Our data showed that the annual incidence of emergency hospital admission among patients with PID is 3.4%. The leading cause of emergency hospital admission was an acute infection, and having a central venous catheter was associated with a significantly greater risk of admission for an infectious episode