Click Metallodendrimers And Their Functions

Click chemistry involving copper-catalyzed azide-alkyne cycloaddition (CuAAC) is one of the most useful and powerful methods to construct metallodendrimers. The design of such strategies includes the choice of the copper(I) catalyst source which is critical in the case of the click synthesis of dendrimers. The 1,2,3-triazolyl-containing dendrimers that are produced provide useful intradendritic ligands that are active in supramolecular recognition and catalysis. This account dedicated to K. Peter C. Vollhardt summarizes work conducted mainly in the authors' Bordeaux laboratory. 1 Introduction 2 Click Copper Catalyzed Azide-Alkyne Cycloaddition Metallodendrimer Constructions 3 The Copper-Catalyzed Azide-Alkyne Cycloaddition Reactions in Dendrimers: Mind the Copper(I) Catalyst 4 Redox Recognition with Triazolylferrocenyl- and Triazolylbiferrocenyl-Terminated Dendrimers 5 Click Catalysis with Extremely Efficient Intradendritic Triazolyl-Copper(I) Complexes 6 Click Dendrimers as Stabilizers for Very Efficient Nanoparticle Catalysis of Cross-Coupling Carbon-Carbon Bond Formation and Redox Reactions 7 Click Dendrons and Dendrimers for Efficient Catalysis Using Magnetically Recoverable Catalysts 8 Conclusion and Prospects26111437144

Interactions between p-Akt and Smad3 in injured muscles initiate myogenesis or fibrogenesis

In catabolic conditions such as aging and diabetes, IGF signaling is impaired and fibrosis develops in skeletal muscles. To examine whether impaired IGF signaling initiates muscle fibrosis, we generated IGF-IR+/- heterozygous mice by crossing loxP-floxed IGF-IR (exon 3) mice with MyoD-cre mice. IGF-IR+/- mice were studied because we were unable to obtain homozygous IGF-IR-KO mice. in IGF-IR+/- mice, both growth and expression of myogenic genes (MyoD and myogenin; markers of satellite cell proliferation and differentiation, respectively) were depressed. Likewise, in injured muscles of IGF-IR+/- mice, there was impaired regeneration, depressed expression of MyoD and myogenin, and increased expression of TGF-beta 1, alpha-SMA, collagen I, and fibrosis. To uncover mechanisms stimulating fibrosis, we isolated satellite cells from muscles of IGF-IR+/- mice and found reduced proliferation and differentiation plus increased TGF-beta 1 production. in C2C12 myoblasts (a model of satellite cells), IGF-I treatment inhibited TGF-beta 1-stimulated Smad3 phosphorylation, its nuclear translocation, and expression of fibronectin. Using immunoprecipitation assay, we found an interaction between p-Akt or Akt with Smad3 in wild-type mouse muscles and in C2C12 myoblasts; importantly, IGF-I increased p-Akt and Smad3 interaction, whereas TGF-beta 1 decreased it. Therefore, in muscles of IGF-IR+/- mice, the reduction in IGF-IR reduces p-Akt, allowing for dissociation and nuclear translocation of Smad3 to enhance the TGF-beta 1 signaling pathway, leading to fibrosis. Thus, strategies to improve IGF signaling could prevent fibrosis in catabolic conditions with impaired IGF signaling.Satellite HealthAmerican Diabetes AssociationNational Institute of Diabetes and Digestive and Kidney DiseasesBaylor Coll Med, Div Nephrol, Dept Med, Houston, TX 77030 USAEmory Univ, Dept Med, Div Renal, Atlanta, GA 30322 USACapital Med Univ, Beijing An Zhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing, Peoples R ChinaUniversidade Federal de São Paulo, Div Nephrol, Dept Med, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Dept Med, São Paulo, BrazilAmerican Diabetes Association: 1-11-BS-194National Institute of Diabetes and Digestive and Kidney Diseases: R37-DK-37175National Institute of Diabetes and Digestive and Kidney Diseases: T32-DK-62706Web of Scienc

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Inhibition of Stat3 Activation Suppresses Caspase-3 and the Ubiquitin-Proteasome System, Leading to Preservation of Muscle Mass in Cancer Cachexia

Cachexia occurs in patients with advanced cancers. Despite the adverse clinical impact of cancer-induced muscle wasting, pathways causing cachexia are controversial, and clinically reliable therapies are not available. A trigger of muscle protein loss is the Jak/Stat pathway, and indeed, we found that conditioned medium from C26 colon carcinoma (C26) or Lewis lung carcinoma cells activates Stat3 (p-Stat3) in C2C12 myotubes. We identified two proteolytic pathways that are activated in muscle by p-Stat3; one is activation of caspase-3, and the other is p-Stat3 to myostatin, MAFbx/Atrogin-1, and MuRF-1 via CAAT/enhancer-binding protein delta (C/EBP delta). Using sequential deletions of the caspase-3 promoter and CHIP assays, we determined that Stat3 activation increases caspase-3 expression in C2C12 cells. Caspase-3 expression and proteolytic activity were stimulated by p-Stat3 in muscles of tumor-bearing mice. in mice with cachexia caused by Lewis lung carcinoma or C26 tumors, knock-out of p-Stat3 in muscle or with a small chemical inhibitor of p-Stat3 suppressed muscle mass losses, improved protein synthesis and degradation in muscle, and increased body weight and grip strength. Activation of p-Stat3 stimulates a pathway from C/EBP delta to myostatin and expression of MAFbx/Atrogin-1 and increases the ubiquitin-proteasome system. Indeed, C/EBP delta KO decreases the expression of MAFbx/Atrogin-1 and myostatin, while increasing muscle mass and grip strength. in conclusion, cancer stimulates p-Stat3 in muscle, activating protein loss by stimulating caspase-3, myostatin, and the ubiquitin-proteasome system. These results could lead to novel strategies for preventing cancer-induced muscle wasting.Satellite HealthAmerican Diabetic AssociationDiabetes Research Center at Baylor College of MedicineNational Institutes of HealthCancer Prevention and Research Institute of TexasAlkek FoundationDan L. Duncan Cancer CenterFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Baylor Coll Med, Div Nephrol, Dept Med, Houston, TX 77030 USABaylor Coll Med, Dept Med, Sect Infect Dis, Houston, TX 77030 USABaylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USABaylor Coll Med, Dept Biochem & Mol Biol, Houston, TX 77030 USAUniversidade Federal de São Paulo, Dept Med, Div Nephrol, BR-04023900 São Paulo, BrazilSichuan Univ, Coll Life Sci, Chengdu 610065, Peoples R ChinaCapital Med Univ, An Zhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing 100029, Peoples R ChinaUniversidade Federal de São Paulo, Dept Med, Div Nephrol, BR-04023900 São Paulo, BrazilAmerican Diabetic Association: 1-11-BS-194Diabetes Research Center at Baylor College of Medicine: P30-DK079638National Institutes of Health: R37 DK37175National Institutes of Health: P50 CA058183National Institutes of Health: P50 CA097007National Institutes of Health: R21 CA149783Cancer Prevention and Research Institute of Texas: RP100421FAPESP: FAPESP 2012/03142-8Web of Scienc

Glucocorticoids increase adipocytes in muscle by affecting IL-4 regulated FAP activity

An increase in intramuscular adipocyte tissue (IMAT) is associated with glucose dysregulation, decreased muscle strength, and increased risk of disability. Unfortunately, the mechanisms stimulating intramuscular adipogenesis remain unclear. We found that dexamethasone (Dex) administration to mice with injured muscles stimulates the accumulation of IMAT. To identify precursors of these adipocytes, we isolated satellite cells and fibro/adipogenic progenitors (FAPs) from muscle; satellite cells did not differentiate into adipocytes even following Dex treatment. in contrast, Dex stimulated FAP differentiation into adipocytes. in vivo, we transplanted purified FAPs from transgenic, EGFP mice into the injured muscles of C57/BL6 mice and found that Dex administration stimulated adipogenesis from FAP-EGFP. the increase in adipogenesis depended on Dex-induced inhibition of interleukin-4 (IL-4). in the injured muscle of IL-4-knockout mice, the levels of adipocytes were increased, while in the injured muscles of Dex-treated mice with IL-4 injections, adipogenesis was suppressed. in cultured FAPs, IL-4 inhibited Dex-induced conversion of FAPs into adipocytes; this did not occur in FAPs expressing knockdown of the IL-4 receptor. Thus, we concluded that glucocorticoids stimulate FAPs to differentiate into adipocytes in injured muscles. This process is blocked by IL-4, suggesting that interfering with IL-4 signaling could prevent adipogenesis in muscle.Satellite HealthAmerican Diabetic AssociationU.S. National Institutes of Health (NIH)Cytometry and Cell Sorting Core at Baylor College of MedicineNIHPilot/Feasibility Program of the Diabetes Research Center at Baylor College of MedicineBaylor Coll Med, Div Nephrol, Houston, TX 77030 USACapital Med Univ, Beijing Zhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing, Peoples R ChinaUniversidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, BrazilAmerican Diabetic Association: 1-11-BS-194U.S. National Institutes of Health (NIH): R37 DK37175NIH: AI036211NIH: CA125123NIH: RR024574NIH: P30 DK079638Web of Scienc