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Abstract: The effects of silicon (Si) application on plant growth, pigments, photosynthetic parameters, chlorophyll a (Chl a) fluorescence parameters and nitrogen metabolism were studied in Cucumis sativus L. under cadmium (Cd) toxicity. Compared with the control, 100μM CdCl2 treatment caused dramatic accumulation of Cd in cucumber leaves, greatly induced chlorosis, and the transmission electron microscope (TEM) analysis indicated that Cd treatment cucumber chloroplast showed obvious swollen, thylakoids and chloroplast membrane were seriously damaged, and could not be observed clearly. Application of Si reversed the chlorosis, protected the chloroplast from disorganization, and significantly increased the pigments contents, which might be mainly responsible for the higher photosynthetic rate and accumulation of biomass under Cd stress. Further investigation of chlorophyll a fluorescence indicated that Cd treatment decreasing photosynthesis was not due to stomatal restriction, while was closely related integrity damage or function lost of the photosynthetic machinery which can be concluded from the higher intercellular CO2 concentration (Ci) and lower F v/F m and ΦPSII. Application of Si alleviated the inhibited level of photosynthesis and F v/F m and ΦPSII by Cd, which might imply that Si plays important roles in protecting photosynthetic machinery from damaging. The Cd treatment also greatly inhibited the enzymes of nitrogen metabolism including nitrogen reductase (NR), glutamine synthetase (GS), glutamate synthase (GOGAT) and glutamate dehydrogenase (GDH), and Si supply decreased the inhibiting effects of Cd. [Copyright &y& Elsevier]

Mutated epidermal growth factor receptor (EGFR) is a major driver of non-small cell lung cancer (NSCLC). The EGFR T790M secondary mutation has become a leading cause of clinically-acquired resistance to gefitinib and erlotinib. Herein, we present a structure-based design approach to increase the potency and selectivity of the previously reported reversible EGFR inhibitor 7 , at the kinase and cellular levels. Three-step structure-activity relationship exploration led to promising compounds 19e and 19h with unique chemical structure and binding mode from the other third-generation tyrosine kinase inhibitors. In a human NSCLC xenograft model, 19e and 19h exhibited dose-dependent tumor growth suppression without toxicity. These selective inhibitors are promising drug candidates for EGFR T790M -driven NSCLC. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is a major cause of acute respiratory failure in critically-ill patients. Resveratrol and curcumin are proven to have potent anti-inflammatory efficacy, but their clinical application is limited by their metabolic instability. Here, a series of resveratrol and the Mono-carbonyl analogs of curcumin (MCAs) hybrids were designed and synthesized by efficient aldol construction strategy, and then screened for anti-inflammatory activities in vitro and in vivo . The results showed that the majority of analogs effectively inhibited the LPS-induced production of IL-6 and TNF-α. Five analogs, a9, a18, a19, a20 and a24 exhibited excellent anti-inflammatory activity in a dose-dependent manner along with low toxicity in vitro . Structure activity relationship study revealed that the electron-withdrawing groups at meta-position and methoxyl group ( OCH 3 ) at the para position of the phenyl ring were important for anti-inflammatory activities. The most promising compound a18 decreased LPS induced TNF-α, IL-6, IL-12, and IL-33 mRNA expression. Additionally, a18 significantly protected against LPS-induced acute lung injury in the in vivo mouse model. The research of resveratrol and MCAs hybrids could bring insight into the treatment of inflammatory diseases and compound a18 may serve as a lead compound for the development of anti-ALI agents. [ABSTRACT FROM AUTHOR]

Curcumin is a nontoxic phenolic compound that modulates the activity of several cellular targets that have been linked with cancers and other chronic diseases. However, the efficacy of curcumin in the clinic has been limited by its poor bioavailability and rapid metabolism in vivo . We have previously reported the design and discovery of series of 5-carbon linker-containing mono-carbonyl analogues of curcumin (MACs) as anti-cancer agents. In continuation of our ongoing research, we designed and synthesized 37 novel long-chain alkoxylated MACs for anti-cancer evaluation here. The MTS assay was used to determine the cytotoxicity of compounds in gastrointestinal cancer cells. Compounds 5 , 28 , and 29 showed strongest inhibition against gastric cancer cell proliferation and were subjected to further analysis. The effects of 5 , 28 , and 29 on cell apoptosis were measured by flow cytometry. Expression levels of Bcl-2, cleaved poly ADP-ribose polymerase (PARP), and pro-caspase-3 were detected by western blotting. Compounds 5 , 28 , and 29 induced apoptosis in human gastric carcinoma cells, increased PARP cleavage, and decreased expression of Bcl-2 and pro-caspase-3 protein. We then showed that compound 28 , which possessed the strongest activity among the test compounds in vitro , exhibited significant tumor inhibition in SGC7901-driven xenograft mouse model. Taken together, the novel compound 28 could be further explored as an effective anticancer agent for the treatment of human gastric cancer. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is a major cause of acute respiratory failure in critically-ill patients. It has been reported that both resveratrol and chalcone derivatives could ameliorate lung injury induced by inflammation. A series of paralleled Aza resveratrol–chalcone compounds ( 5a – 5m , 6a – 6i ) were designed, synthesized and screened for anti-inflammatory activity. A majority showed potent inhibition on the IL-6 and TNF-α expression-stimulated by LPS in macrophages, of which compound 6b is the most potent analog by inhibition of LPS-induced IL-6 release in a dose-dependent manner. Moreover, 6b exhibited protection against LPS-induced acute lung injury in vivo. These results offer further insight into the use of Aza resveratrol–chalcone compounds for the treatment of inflammatory diseases, and the use of compound 6b as a lead compound for the development of anti-ALI agents. [ABSTRACT FROM AUTHOR]

Obesity has been recognized as a major risk factor for the development of chronic cardiomyopathy, which is associated with increased cardiac inflammation, fibrosis, and apoptosis. We previously developed an anti-inflammatory compound C66, which prevented inflammatory diabetic complications via targeting JNK. In the present study, we have tested the hypothesis that C66 could prevent obesity-induced cardiomyopathy by suppressing JNK-mediated inflammation. High-fat diet (HFD)-induced obesity mouse model and palmitic acid (PA)-challenged H9c2 cells were used to develop inflammatory cardiomyopathy and evaluate the protective effects of C66. Our data demonstrate a protective effect of C66 against obesity-induced cardiac inflammation, cardiac hypertrophy, fibrosis, and dysfunction, overall providing cardio-protection. C66 administration attenuates HFD-induced myocardial inflammation by inhibiting NF-κB and JNK activation in mouse hearts. In vitro , C66 prevents PA-induced myocardial injury and apoptosis in H9c2 cells, accompanied with inhibition against PA-induced JNK/NF-κB activation and inflammation. The protective effect of C66 is attributed to its potential to inhibit JNK activation, which led to reduced pro-inflammatory cytokine production and reduced apoptosis in cardiomyocytes both in vitro and in vivo. In summary, C66 provides significant protection against obesity-induced cardiac dysfunction, mainly by inhibiting JNK activation and JNK-mediated inflammation. Our data indicate that inhibition of JNK is able to provide significant protection against obesity-induced cardiac dysfunction. [Display omitted] • Compound C66 attenuated cardiomyopathy in HFD-fed mice. • C66 reduced PA-induced inflammation and apoptosis via inhibiting JNK activation. • Inhibition of inflammation prevents obesity-associated cardiomyopathy. • JNK is a promising therapeutic target for obesity-induced myocardial injury. [ABSTRACT FROM AUTHOR]

Obesity has been recognized as a major risk factor for the development of chronic kidney disease, which is accompanied by increased renal inflammation, fibrosis, and apoptosis. C66 is a curcumin derivative that exerts anti-inflammatory effects by inhibiting the JNK pathway and prevents diabetic nephropathy. The present study investigates the possible protective effect of C66 on high-fat diet (HFD)-induced obesity-related glomerulopathy. Mice were fed with HFD for 8 weeks while some were treated with C66 every 2 days for 11 weeks. The HFD-fed mice developed renal dysfunction, as well as elevated triglyceride and cholesterol. Kidneys of the HFD-fed mice showed marked glomerular injuries, apoptosis, and inflammation with markedly increased cytokine production. Interestingly, treating HFD-fed mice with C66 remarkably reversed these pathological changes via inhibiting inflammation and NF-κB/JNK activation. In cultured mesangial cells, Palmitic Acid was able to activate the pro-fibrotic mechanisms, apoptosis, inflammatory response, and NF-κB and JNK signaling pathways, all of which could be attenuated by C66 treatment. In all, we demonstrated that curcumin analogue C66 attenuates obesity-induced renal injury by inhibiting chronic inflammation and apoptosis via targeting NF-κB and JNK. Our data suggest that C66 can be potentially used to prevent obesity-associated renal diseases warranting future investigations. [Display omitted] • Compound C66 improved histological abnormalities in HFD-fed mouse kidney. • C66 reduced PA-induced inflammation and apoptosis in mesangial cells. • C66 attenuated inflammatory kidney injuries via inhibiting JNK/NF-κB activation. • Inhibition of inflammation may be an effective strategy for the treatment of ORG. • JNK/NF-κB pathway is a promising therapeutic target for ORG. [ABSTRACT FROM AUTHOR]

Hierarchically nanostructured carbon hybrids with highly exposed active sites and specific surface area have been widely researched in high-performed electrochemical capacitors. Inspired from the synergistic effect of uniformly distributed active components and stable carbon substrate, combining with green solvent extraction process, we explored a facile strategy to prepare vanadium nitride quantum dots/nitrogen-doped hierarchical carbon nanocomposites (VNQD/NDHCs) from vanadium aqueous solution, which can provide large pseudocapacitance and excellent electrochemical stability. Vanadate is selective recovered from aqueous solution in form of vanadium-organic compounds (VAORCs) as precursor. Primary amines favor not only the selective metal-polymer coordination, but also the formation of cross-linked carbon matrix. Then, during chemical molecules vapor deposition (CMVD), the vanadate is in-situ nitrided along with the formation of hierarchical carbon. The prepared VNQD/NDHCs-800 exhibits exceptional capacitance (318.3 F g−1 at 1 A g−1) and retains 89.7% of the initial capacities after 12000 cycles. SEM and TEM images confirm that a large amount of quantum dots are well embedded in a graphitic carbon matrix, which provides abundant electroactive sites and fast ion diffusion for capacitive storage. This work indicates that it is feasible to directly recovery valuable metals from aqueous solutions to prepare high-performance electrode materials. Image 1 • Vanadium-based carbon hybrids contain abundant vanadium nitride active sites • Vanadium in aqueous solution is almost completely recycled. • Scalable fabrication of the products based on green solvent extraction process. • The products exhibits exceptional capacitance and excellent cycling stability. [ABSTRACT FROM AUTHOR]