Synthesis and biological evaluation of novel 8- substituted sampangine derivatives as potent inhibitor of Zn2+-Aß complex mediated toxicity, oxidative stress and inflammation.

A series of 8-substituted sampangine derivatives have been designed, synthesized and tested for their ability to inhibit cholinesterase and penetrate the blood-brain barrier. Their chelating ability toward Zn2+ and other biologically relevant metal ions was also demonstrated by isothermal titration calorimetry. The new derivatives exhibited high acetylcholinesterase inhibitory activity, high blood-brain barrier penetration ability and high chelating selectivity for Zn2+. Moreover, compound 10 with the strongest binding affinity to Zn2+ was selected for further research. Western blotting analysis, transmission electron microscopy, DCFH-DA assay and paralysis experiment indicated that compound 10 suppressed the formation of Zn2+-Aß complexes, alleviated the Zn2+ induced neurotoxicity and inhibited the production of ROS catalyzed by Zn2+ in Aß42 transgenic C. elegans. Furthermore, compound 10 also inhibited the expressions of pro-inflammatory cytokines, such as NO, TNF-α, IL-6 and IL-1ß, induced by Zn2+ + Aß1-42 in BV2 microglial cells. In general, this work provided new insights into the design and development of potent metal-chelating agents for Alzheimer's disease treatment.

Structures and luminescent sensors of mixed-counterions based salen-type lanthanide coordination polymers.

Reactions of N,N'-bis (salicylidene)-1,2-cyclohexanediamine (H2 L) with mixed lanthanide counterions of LnCl3 ·6H2 O and Ln (NO3 )3 ·6H2 O afford six H2 L lanthanide coordination polymers, e.g. {[Pr(H2 L)2 (NO3 )2 Cl]·2CH2 Cl2 }n (1); {[Ln(H2 L)1.5 (NO3 )3 ]2 ·5CHCl3 ·mCH3 OH}n [Ln = Sm (2), Eu (3), Gd (4), Tb (5) and Yb (6); m = 1 (2-5); m = 0 (6)]. X-ray crystallographic analysis reveals that complex 1 exhibits three-dimensional diamondoid topologic structure and complexes 2-6 are of two-dimensional structure. Luminescent spectra show that complexes 1 and 6 have characteristic near-infrared (NIR) emission of praseodymium (III) and ytterbium (III) ions and complexes 2-5 emit luminescence in the visible region. Complexes 3 and 6 reveal sensitive luminescence responses to formaldehyde.

Near-IR luminescence and field-induced single molecule magnet of four salen-type ytterbium complexes.

A series of rigid hexadentate salen-type (H2L) ytterbium complexes, namely, [Yb2L3(CH3OH)]·3CH3CN (1), [Yb2LL'L″(CH3OH)(H2O)2](ClO4)2·CH3OH·H2O (2), [Yb2L(OAc)4(CH3OH)2]·2CH3OH (3), and {[Yb2L(OAc)4]·3H2O}n (4) (H2L = N,N'-bis(2-oxy-3-methoxybenzylidene)-1,2-phenylenediamine, HL' = 2-(2'-hydroxy-3'-methyloxy-phenyl)benzimidazole and HL" = 3-methoxysalicylaldehyde) have been synthesized by reactions of H2L with multifarious Yb(3+) salts. X-ray crystallographic analyses demonstrate that complex 1 is of a triple-decker sandwich-type Yb2L3 structure with a ratio of H2L/Yb = 3:2, 2 and 3 possess the unique Yb2 core with a ratio of H2L/Yb = 2:2 and 1:2, respectively, 4 exhibits one dimensional coordination polymers in which the polymeric structures are formed by acetate (OAc(-)) groups. All complexes 1-4 exhibit near-IR luminescence, which can be rationalized on the basis of the disparate structural effects. The magnetic analysis unveils that all complexes 1-4 are of field-induced single-molecule magnet behavior with the energy barriers (Ueff/kB) of 14.5, 2.0, 9.5, and 2.4 K at 3 kOe direct current fields, respectively.

Lung transcriptome analysis for the identification of genes involved in the hypoxic adaptation of plateau pika (Ochotona curzoniae).

The plateau pika, a typical hypoxia-tolerant mammal lives 3000-5000 m above sea level on the Qinghai-Tibet Plateau, has acquired many physiological and morphological characteristics and strategies in its adaptation to sustained, high-altitude hypoxia. Blunted hypoxic pulmonary vasoconstriction is one such strategy, but the genes involved in this strategy have not been elucidated. Here, we investigated the genes involved and their expression profiles in the lung transcriptome of plateau pikas subjected to different hypoxic conditions (using low-pressure oxygen cabins). A slight, right ventricular hypertrophy was observed in pikas of the control group (altitude: 3200 m) vs. those exposed to 5000 m altitude conditions for one week. Our assembly identified 67,774 genes; compared with their expression in the control animals, 866 and 8364 genes were co-upregulated and co-downregulated, respectively, in pikas subjected to 5000 m altitude conditions for 1 and 4 w. We elucidated pathways that were associated with pulmonary vascular arterial pressure, including vascular smooth muscle contraction, HIF-1 signalling, calcium signalling, cGMP-PKG signalling, and PI3K-Akt signalling based on the differentially expressed genes; the top-100 pathway enrichments were found between the control group and the group exposed to 5000 m altitude conditions for 4 w. The mRNA levels of 18 candidate gene showed that more than 83% of genes were expressed and the number of transcriptome The up-regulated genes were EPAS1, Hbα, iNOS, CX40, CD31, PPM1B, HIF-1α, MYLK, Pcdh12, Surfactant protein B, the down-regulated genes were RYR2, vWF, RASA1, CLASRP, HIF-3α. Our transcriptome data are a valuable resource for future genomic studies on plateau pika.

MiR-10a-5p restrains the aggressive phenotypes of ovarian cancer cells by inhibiting HOXA1.

MicroRNAs (miRNAs) are dysregulated in human ovarian carcinoma (OC). But the mechanism underlying miR-10a-5p in regulating the progression of OC need deeply explored. In the current study, we observed that miR-10a-5p was down-expressed in OC samples and OC cell lines. In addition, miR-10a-5p restrained the viability, colony formation, migration ability and invasiveness of OC cells. We further ascertained Homeobox A1 (HOXA1) was a downstream gene of miR-10a-5p. Furthermore, HOXA1 was distinctly upregulated in OC samples. Finally, upregulation of HOXA1 abolished the suppressive effects of miR-10a-5p on OC cells. These observations suggested that miR-10a-5p suppressed the aggressive phenotypes of OC cells via regulating HOXA1.

Novel sampangine derivatives as potent inhibitors of Cu2+-mediated amyloid-ß protein aggregation, oxidative stress and inflammation.

A series of 11-substituted sampangine derivatives have been designed, synthesized, and tested for their ability to inhibit cholinesterase. Their chelating ability and selectivity for Cu2+ over other biologically relevant metal ions were demonstrated by isothermal titration calorimetry. Their blood-brain barrier permeability was also tested by parallel artificial membrane permeation assay. Among the synthesized derivatives, compound 11 with the strong anti-acetylcholinesterase activity, high blood-brain barrier penetration ability and high binding affinity to Cu2+ was selected for further research. Western blotting analysis, transmission electron microscopy, DCFH-DA assay and paralysis experiment indicated that compound 11 suppressed the formation of Cu2+-Aß complexes, alleviated the Cu2+ induced neurotoxicity and inhibited the production of ROS catalyzed by Cu2+ in Aß42 transgenic C. elegans. Moreover, compound 11 also inhibited the expressions of proinflammatory cytokines, such as NO, TNF-α, IL-6 and IL-1ß, induced by Cu2+ + Aß1-42 in BV2 microglial cells. In general, this work provided new insights into the design and development of potent metal-chelating agents for AD treatment.

Increased lipopolysaccharide content is positively correlated with glucocorticoid receptor-beta expression in chronic rhinosinusitis with nasal polyps.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and frequently occurring disease of the upper respiratory tract. The nasal instillation of the Gram-negative (G- ) bacterial product lipopolysaccharide (LPS) can induce not only acute sinusitis but also the development of CRSwNP in animal models. Nevertheless, the expression and distribution of LPS in patients with CRSwNP have not been investigated. And the study was to investigate the expression of LPS and its relationship with glucocorticoid receptors (GRs) in CRSwNP. METHODS: Multiple methods, including bacterial culture and immunohistochemistry, were used to detect and analyze nasal bacteria, plasma LPS content, and the levels of LPS and GR-α/ß, cluster of differentiation 68 (CD68), and myeloperoxidase (MPO) expression, as well as their relationship in CRSwNP. RESULTS: The number of G- bacteria and Escherichia coli (E. coli) was not significantly different between CRSwNP subjects and the controls. However, the positive rate of LPS was much higher than that of E. coli in CRSwNP subjects and was significantly higher in noneosinophilic CRSwNP subjects than in eosinophilic CRSwNP subjects. Moreover, the LPS levels were positively correlated with GR-ß but not GR-α expression in CRSwNP. Immunofluorescence assays showed that LPS was mainly detected in CD68+ macrophages and MPO+ neutrophils, in addition to histiocytes, in CRSwNP. CONCLUSIONS: Persistent LPS in CRSwNP can lead to unresolved mucosal inflammation, eventually leading to tissue remodeling and the development of CRSwNP. Our findings suggest that increased LPS content and possible resistance to glucocorticoids may be one of the important pathogenic mechanisms of G- bacteria in CRSwNP.

[Gene mutational analyses of cathepsin C gene in a family with Papillon-Lefèvre syndrome].

OBJECTIVE: This study aimed to investigate the gene mutational characteristics of cathepsin C (CTSC) gene in a Chinese patient with Papillon-Lefèvre syndrome (PLS) and further confirm the genetic basis for the phenotype of PLS. METHODS: Peripheral blood samples were obtained from the PLS proband and his family members (his parents and younger brother) for genomic DNA extraction. The coding region and exon boundaries of the CTSC gene were amplified and sequenced by polymerase chain reaction and direct sequencing of DNA. RESULTS: Compound heterozygous mutations of CTSC gene were identified in the patient. A heterozygous missense mutation occurred in the 800th base of exon 6, and the base T in the base pair was replaced by C (c.800T>C). The encoded amino acid leucine changed to proline (p. L267P). A heterozygous missense mutation occurred in the 1015th base of exon 7, and base C in the base pair was replaced by T (c.1015C>T). The encoded amino acid arginine changed to cysteine (p.R339C). Among the mutations, c.800T>C originated from the mother, c.1015C>T was identified from the father. No mutations were detected in the younger brother. CONCLUSIONS: Mutations of CTSC gene are responsible for the phenotype of PLS.

[Study on the technique of ultrasonic wave extraction of triterpeneclucoside].

The extraction technique of ultrasonic wave on increasing the triterpeneclucoside was studied. Based on single factor experiments and the orthogonal design introduced,the optimized extracting conditions of triterpeneclucoside were investigated. The results showed that the best extraction technique conditons are 65% alcohol-water, the ratio of solid to liquid 1:30,dousing over 30 minutes,ultrasonic wave lasting for 40 minutes, ultrasonic frequency 26.8 KHZ, ultrasonic (output) power 1080 kw and extraction temperature 40 degrees C, respectively.

Evaluation of sensory function and recovery after replantation of fingertips at Zone I in children.

Sensory function is the most significant criterion when evaluating the prognosis of replanted fingers. Current clinical research has focused on surgical techniques and indications for finger replantation; however, few studies have focused on recovery of finger sensory function after replantation. This study retrospectively assessed data of eight patients who had undergone nine Zone I replantations of the fingertips in the First Affiliated Hospital of Sun Yat-sen University of China from July 2014 to January 2016. Variations in the extent of damage, with the residual vessels or nerves in some fingers being too short or even missing, prevented tension-free suture repair in some patients. Thus, repair of four of the nine fingertips included arteriovenous anastomosis, the remaining five undergoing arterial anastomosis during replantation of the amputated fingers. Three patients underwent nerve repair, whereas the remaining six cases did not. Fingertip replantations were successful in all eight patients. Compared with the patients without vascular anastomosis, no obvious atrophy was visible in the fingertips of patients who did undergo vascular anastomosis during replantation and their sensory function did recover. Fingertip replantation provides good sensory function and cosmetic outcomes when good artery and vein anastomoses have been created, even when digital nerves have not been repaired.