RESUMO
The precise control of the regioselectivity in the transition metal-catalyzed migratory hydrofunctionalization of alkenes remains a big challenge. With a transient ketimine directing group, the nickel-catalyzed migratory ß-selective hydroarylation and hydroalkenylation of alkenyl ketones has been realized with aryl boronic acids using alkyl halide as the mild hydride source for the first time. The key to this success is the use of a diphosphine ligand, which is capable of the generation of a Ni(II)-H species in the presence of alkyl bromide, and enabling the efficient migratory insertion of alkene into Ni(II)-H species and the sequent rapid chain walking process. The present approach diminishes organosilanes reductant, tolerates a wide array of complex functionalities with excellent regioselective control. Moreover, this catalytic system could also be applied to the migratory hydroarylation of alkenyl azahetereoarenes, thus providing a general approach for the preparation of 1,2-aryl heteroaryl motifs with wide potential applications in pharmaceutical discovery.
RESUMO
To explore the mechanism of microRNA-155 (miR-155) deficiency, protecting against experimental autoimmune prostatitis (EAP) in a toll-like receptor 4 (TLR4)-dependent manner. After wild-type (WT) and miR-155-/- mice were injected with complete Freund's adjuvant and prostate antigen to establish EAP model, half were randomly selected for injection with lipopolysaccharide (LPS, a TLR4 ligand). The following experiments were then performed: von Frey filaments, hematoxylin-eosin (HE) staining, real time quantitative polymerase chain reaction (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). And the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the level of Malondialdehyde (MDA) were detected by corresponding kits.miR-155-/- mice with prostatitis exhibited the attenuated pelvic tactile allodynia/hyperalgesia and the suppressed TLR4/nuclear factor-kappa B (NF-κB) pathway as compared with the WT mice with prostatitis. In addition, LPS enhanced the upregulation of miR-155 and the activation of the TLR4/NF-κB pathway in the prostatic tissues of WT mice with EAP. Furthermore, prostatitis mice had aggravated inflammation scores accompanying the increased interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, interferon-γ, IL-12, and MDA in prostatic tissues with the decreased IL-10, SOD and GSH-Px, and the unaltered IL-4. Compared with the mice from the WT + EAP group and the miR-155-/- + EAP + LPS group, mice from the miR-155-/- + EAP group had decreased inflammation and oxidative stress. miR-155 deficiency ameliorated pelvic tactile allodynia/hyperalgesia in EAP mice and improved inflammation and oxidative stress in prostatic tissues in a TLR4-dependent manner involving NF-κB activation, thereby exerting a therapeutic effect in chronic prostatitis treatment.
Assuntos
Doenças Autoimunes/genética , Hiperalgesia/genética , MicroRNAs/genética , NF-kappa B/genética , Prostatite/genética , Receptor 4 Toll-Like/genética , Animais , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/imunologia , Doenças Autoimunes/prevenção & controle , Modelos Animais de Doenças , Adjuvante de Freund/administração & dosagem , Regulação da Expressão Gênica , Glutationa Peroxidase/genética , Glutationa Peroxidase/imunologia , Hiperalgesia/induzido quimicamente , Hiperalgesia/imunologia , Hiperalgesia/prevenção & controle , Interferon gama/genética , Interferon gama/imunologia , Interleucina-12/genética , Interleucina-12/imunologia , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Lipopolissacarídeos/farmacologia , Masculino , Malondialdeído/imunologia , Malondialdeído/metabolismo , Camundongos , Camundongos Knockout , MicroRNAs/imunologia , NF-kappa B/imunologia , Estresse Oxidativo , Antígeno Prostático Específico/administração & dosagem , Prostatite/induzido quimicamente , Prostatite/imunologia , Prostatite/prevenção & controle , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/imunologia , Receptor 4 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
BACKGROUND: Adrenomedullin levels in the peripheral blood are associated with prognosis of some cancers. Intermedin is structural similarities to adrenomedullin. OBJECTIVE: The current study aimed to investigate the prognostic value of plasma intermedin levels for progression and distant metastasis in prostate cancers. METHODS: This study included 218 patients undergoing radical prostatectomy for localized prostatic cancer and 218 age-matched healthy men. Plasma intermedin levels were measured using radioimmunoassay. The relationships between plasma intermedin levels and 5-year progression and 5-year distant metastasis were evaluated using a multivariate analysis. RESULTS: Plasma intermedin levels were markedly higher in all patients than in healthy men. Patients with Gleason score ≥ 7, tumor node metastasis stage T2, organ unconfined, present extra-prostatic extension, seminal vesicle invasion or positive lymph node had higher intermedin levels. Intermedin was identified as a prognostic predictor for 5-year progression and 5-year metastasis. Under receiver operating characteristic curves, intermedin had high predictive values for 5-year progression and 5-year metastasis. CONCLUSIONS: Elevated plasma intermedin levels are independently associated with long-term recurrence and distant metastasis of prostate cancer and intermedin has potential to be a prognostic predictive biomarker for prostate cancer.
