RESUMO
An OSMAC strategy was used to study secondary metabolites and anti-inflammatory activities of the endophytic fungus Penicillium herquei JX4 hosted in Ceriops tagal. The PDB ferment of fungus P. herquei JX4 was isolated, purified, and identified by using silica gel column chromatography, gel column chromatography, octadecylsilyl(ODS) column chromatography, and semi-preparative high-performance liquid chromatography. Two new pinophol derivatives, pinophol H(1) and pinophol I(2) were isolated and identified, and they were evaluated in terms of the inhibitory activities against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse macrophage RAW264.7 cells. The results showed that compound 1 had significant inhibitory activity on NO production, with an IC_(50) value of 8.12 µmol·L~(-1).
Assuntos
Óxido Nítrico , Penicillium , Penicillium/química , Camundongos , Animais , Células RAW 264.7 , Macrófagos/efeitos dos fármacos , Endófitos/química , Estrutura Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/químicaRESUMO
At the level of in vitro drug screening, the development of a phenotypic analysis system with high-content screening at the core provides a strong platform to support high-throughput drug screening. There are few systematic reports on brain organoids, as a new three-dimensional in vitro model, in terms of model stability, key phenotypic fingerprint, and drug screening schemes, and particularly regarding the development of screening strategies for massive numbers of traditional Chinese medicine monomers. This paper reviews the development of brain organoids and the advantages of brain organoids over induced neurons or cells in simulated diseases. The paper also highlights the prospects from model stability, induction criteria of brain organoids, and the screening schemes of brain organoids based on the characteristics of brain organoids and the application and development of a high-content screening system.
RESUMO
Hebbian-type synaptic plasticity which includes long term potentiation (LTP) and long term depression (LTD), is the main cellular mechanism underlying learning and memory. Effective activity and synaptic content of tyrosine phosphatase SHP2 are required for AMPA receptor trafficking during LTP. However, the role of SHP2 in LTD has not been fully elucidated. This study shows that the phosphorylation level of SHP2 at Y542 decreased after LTD induction either in hippocampal cultures or acute CA1 mini slices. This change occurred at least 10 min after LTD induction and was alleviated by administration of NMDA receptor antagonist, APV. Furthermore, the SHP2 mutant (D61G), found in Noonan syndrome patients, prevented the removal of surface AMPA receptors during chemical-induced LTD on cultured hippocampal neurons. The results revealed a molecular basis of regulatory role of SHP2 in long term depression, thus expands our understanding of the SHP2 function in learning and memory.
Assuntos
Potenciação de Longa Duração , Depressão Sináptica de Longo Prazo , Proteína Tirosina Fosfatase não Receptora Tipo 11 , Receptores de AMPA , Regulação para Baixo , Hipocampo/metabolismo , Humanos , Potenciação de Longa Duração/fisiologia , Depressão Sináptica de Longo Prazo/fisiologia , Plasticidade Neuronal , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Receptores de AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inibidoresRESUMO
OBJECTIVE: To study the diagnosis of adult nutcracker phenomenon (NCP) and assess the therapeutic value of endovascular stenting (ES) and superior mesentery artery transposition (SMAT) for the treatment of NCP in long-term follow-up. METHODS: Six patients (6 men) aged 16 and 34 years old (mean age, 22.7 +/- 18.0 years) were diagnosed as having NCP using the examination of the doppler ultrasound and/or magnetic resonance of artery/digital radiography (MRA/DSA). Three patients underwent ES and 3 patients received SMAT for the treatment of the NCP patients associated with recurrent gross hematuria and left flank pain. Doppler ultrasound and urine examination were used at pre- and post-operation. RESULTS: In 3 patients who underwent SMAT, the postoperative complications comprised retroperitoneal hematoma necessitating surgical revision (n = 1). Functional disorder of intestine (n = 1) and paralytic ileus (n = 1) that were resolved by conservative management. In 3 patients who experienced ES, 1 patient received surgical revision because the position of stent was not suitable in left renal vein but no other complication took place. During the follow-up of 6 approximately 50 months (mean 24.7 +/- 18.0 months), except that 1 patient's hematuria disappears at rest and reappears after motion while the other 5 patients remain asymptomatic and free of hematuria. The dopplar ultrasound showed the left renal vein diameters of the angel segment between superior mesentery artery and aorta were (0.18 +/- 0.05) cm preoperation and (0.65 +/- 0.17) cm postoperation, P < 0.001; the left renal vein diameters of the portal segment were (0.89 +/- 0.22) cm preoperation and (0.79 +/- 0.20) cm postoperation, P = 0.003; the left renal vein diameter's ratio between portal and angel segment were (4.99 +/- 0.79) preoperation and (1.23 +/- 0.16) postoperation, P < 0.001. CONCLUSIONS: Dopplar ultrasound plays a very important role in the diagnosis of adult NCP. SMAT is an efficient surgical approach to the treatment of the nutcracker phenomenon and is associated with an acceptable risk of complications. But ES is safer and more efficient than SMAT and may represent a valuable approach to lessening the morbidity of surgical procedures. ES is a new therapeutic method for adult NCP.