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Endothelial dysfunction is characterized by disturbances in nitric oxide (NO) bioavailability and increased circulating asymmetric dimethylarginine (ADMA) due to the enormous release of free radicals. Increased circulating ADMA may cause endothelial dysfunction and a variety of clinical disorders, such as liver and kidney disease. Young male Sprague-Dawley rats at postnatal day 17 ± 1 received continuous ADMA infusion via an intraperitoneal pump to induce endothelial dysfunction. Four groups of rats (n = 10 per group) were allocated: control, control and resveratrol, ADMA infusion, and ADMA infusion and resveratrol groups. Spatial memory, NLR family pyrin-domain-containing 3 (NLRP3) inflammasome, cytokine expression, tight junction proteins in the ileum and dorsal hippocampus, and microbiota composition were examined. We found cognitive deficits; increased NLRP3 inflammasome in the plasma, ileum, and dorsal hippocampus; decreased ileum and dorsal hippocampal cytokine activation and tight junction proteins; and microbiota composition alterations in the ADMA-infusion young male rats. Resveratrol had beneficial effects in this context. In conclusion, we observed NLRP3 inflammasome activation in peripheral and central dysbiosis in young male rats with increased circulating ADMA, and found that resveratrol had beneficial effects. Our work adds to the mounting evidence that inhibiting systemic inflammation is a promising therapeutic avenue for cognition impairment, probably via the gut-brain axis. [ABSTRACT FROM AUTHOR]

With the improvement in children's acute lymphoblastic leukemia (ALL) care, the survival rate in children ALL has improved much. Methotrexate (MTX) plays an essential role in the success of children's ALL treatment. Since hepatotoxicity is commonly reported in individuals treated with intravenous or oral MTX, our study further examined the hepatic effect following intrathecal MTX treatment, which is an essential treatment for leukemia patients. Specifically, we examined the pathogenesis of MTX hepatotoxicity in young rats and explored the impact of melatonin treatment in protection against MTX hepatotoxicity. Successfully, we found that melatonin was able to protect against MTX hepatotoxicity. [ABSTRACT FROM AUTHOR]

Copper ions (Cu2+) play an indispensable role in both the human body and eco-environment, so it is crucial to create simple, highly sensitive and selective sensors to recognize Cu2+ ions. In this work, three efficient iridium(III) complexes, [(L1)2Ir(Czdtc)] (Ir1, L1 = 6-phenylnicotinaldehyde), [(L2)2Ir(Czdtc)] (Ir2, L2 = 6-(4-(trifluoromethyl)phenyl)nicotinaldehyde) and [(L3)2Ir(Czdtc)] (Ir3, L3 = 6-(4-methoxyphenyl)nicotinaldehyde) comprising a four-membered Ir–S–C–S ring backbone with 9H-carbazole-9-carbodithioate (Czdtc) as ancillary ligands, were synthesized within 10 minutes at room temperature, and developed as efficient chemical sensors to detect Cu2+ ions. Ir1–Ir3 exhibited broad emission bands peaking between 575 and 593 nm with PLQY in the range of 0.34–0.70 and lifetimes ranging from 1.3 to 1.8 μs. In acetonitrile solution, they showed a sensitive response to Cu2+ ions with a low detection limit on the order of 10−7 M with a stoichiometric ratio of 1 : 1, and distinct colorimetric changes (from orange-red to greenish-yellow) were observed by the naked eye. Nanofibrous films decorated with these complexes fabricated using the electrospinning technology could realize on-site detection of Cu2+ ions, based on an obvious contrasting luminescence color different from the background under a 365 nm UV lamp. Nanofibrous films decorated with the fast synthesized Ir1–Ir3 could be used as solid-phase sensing devices with low-cost, high efficiency and portability, providing a promising prospect for the detection of Cu2+ ions in the environment. [ABSTRACT FROM AUTHOR]

Pseudopodium enriched atypical kinase 1(PEAK1) is a non-receptor tyrosine kinase, which is enriched in the pseudopodia of migrating cells and plays an important role in regulating cell migration and proliferation. In the study, we investigate the therapeutic effect of PEAK1 on melanoma cells in vitro and in vivo . We used a lentiviral vector to express short hairpin RNAs (Lv-PEAK1 shRNA) for inhibiting PEAK1 expression in the melanoma SKMEL28 cells. A full-length PEAK1 gene was cloned into the pcDNA 3.1 (+) plasmid and used to infect the melanoma SKMEL19 cells. P6 (also known as Pyridines 6, EMD Chemicals), the Pan-JAK inhibitor, was used to inhibit the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway. The cell counting kit-8 (CCK-8), colony formation assay and transwell assay were used to detect cell proliferation, growth and invasion in vitro . The effect of PEAK1 on melanoma progression in vivo was also evaluated. Protein expression of PEAK1, E-cadherin, vimentin and JAK/STAT3 was measured using western blot assay or immunohistochemistry. The results showed that enforced PEAK1 expression facilitated melanoma cell growth, invasion and metastasis via activating JAK/STAT3 signals, and PEAK1 knockdown inhibited melanoma cell growth, invasion and metastasis via inactivating JAK/STAT3 signals. Further work demonstrated that P6 (500 nM) treatment reversed PEAK1-induced effect in melanoma cells. PEAK1 promotes tumorigenesis and metastasis via activating JAK/STAT3 signals, and PEAK1 knockdown reduced tumorigenesis and metastasis in melanoma via inactivating JAK/STAT3 signals, providing a novel therapeutic strategy for melanoma treatment.