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排序方式: 共有196条查询结果,搜索用时 31 毫秒
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Aysan Etemadi Salar Hemmati Mohammad Shahrivar-Gargari Yasaman Tamaddon Abibiglue Ahad Bavili Maryam Hamzeh-Mivehroud Siavoush Dastmalchi 《化学与生物多样性》2023,20(8):e202300075
Indanone derivatives containing meta/para-substituted aminopropoxy benzyl/benzylidene moieties were designed based on the structures of donepezil and ebselen analogs as the cholinesterase inhibitors. The designed compounds were synthesized and their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were measured. Inhibitory potencies (IC50 values) for the synthesized compounds ranged from 0.12 to 11.92 μM and 0.04 to 24.36 μM against AChE and BChE, respectively. Compound 5 c showed the highest AChE inhibitory potency with IC50 value of 0.12 μM, whereas the highest BChE inhibition was achieved by structure 7 b (IC50=0.04 μM). Structure-activity relationship (SAR) analysis revealed that there is no significant difference between meta and para-substituted derivatives in AChE and BChE inhibition. However, the most potent AChE inhibitor 5 c belongs to meta-substituted compounds, while the most active BChE inhibitor is para-substituted derivative 7 b . The order of enzyme inhibition potency based on the substituted amine group is dimethyl amine>piperidine>morpholine. Compounds containing C=C linkage are more potent AChE inhibitors than the corresponding saturated structures. Molecular docking studies indicated that 5 c interacts with AChE in a very similar way to that observed experimentally for donepezil. The introduced indanone-aminopropoxy benzylidenes could be used in drug-discovery against Alzheimer's disease. 相似文献
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A study is presented of a set of coupled nets proposed to function as a global competitive network. One net, of hidden nodes,
is composed solely of inhibitory neurons and is excitatorily driven and feeds back in a disinhibitory manner to an input net
which itself feeds excitatorily to a (cortical) output net. The manner in which the former input and hidden inhibitory net
function so as to enhance outputs as compared with inputs, and the further enhancements when the cortical net is added, are
explored both mathematically and by simulation. This is extended to learning on cortical afferent and lateral connections.
A global wave structure, arising on the inhibitory net in a similar manner to that of pattern formation in a negative laplacian
net, is seen to be important to all of these activities. Simulations are only performed in one dimension, although the global
nature of the activity is expected to extend to higher dimensions. Possible implications are briefly discussed.
Received: 21 November 1993/Accepted in revised form: 30 June 1994 相似文献
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Marcel V. Alavi 《Biochimica et Biophysica Acta - Proteins and Proteomics》2021,1869(2):140558
OMA1 is a mitochondrial protease. Among its substrates are DELE1, a signaling peptide, which can elicit the integrated stress response, as well as the membrane-shaping dynamin-related GTPase OPA1, which can drive mitochondrial outer membrane permeabilization. OMA1 is dormant under physiological conditions but rapidly activated upon mitochondrial stress, such as loss of membrane potential or excessive reactive oxygen species. Accordingly, OMA1 was found to be activated in a number of disease conditions, including cancer and neurodegeneration. OMA1 has a predicted transmembrane domain and is believed to be tethered to the mitochondrial inner membrane. Yet, its structure has not been resolved and its context-dependent regulation remains obscure. Here, I review the literature with focus on OMA1's biochemistry. I provide a good homology model of OMA1's active site with a root-mean-square deviation of 0.9 Å and a DALI Z-score of 19.8. And I build a case for OMA1 actually being an integral membrane protease based on OMA1's role in the generation of small signaling peptides, its functional overlap with PARL, and OMA1's homology with ZMPSTE24. The refined understanding of this important enzyme can help with the design of tool compounds and development of chemical probes in the future. 相似文献
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Moosadoost Yasaman Zendehdel Morteza Khodadadi Mina 《International journal of peptide research and therapeutics》2021,27(1):253-262
International Journal of Peptide Research and Therapeutics - RFamide-related Peptide-3(RFRP-3) plays a key role in appetite regulation. The current study aimed to determine the effect of... 相似文献
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Amir Ali Rahsepar Asadollah Mirzaee Fatemeh Moodi Mohsen Moohebati Shima Tavallaie Fatemeh Khorashadizadeh Ali Eshraghi Maryam-Sadat Alavi Laya Zarrabi Mostafa Sajjadian Maral Amini Roshanak Khojasteh Roghayeh Paydar Somayeh Mousavi Majid Ghayour-Mobarhan Gordon A. Ferns 《Cell stress & chaperones》2013,18(1):65-74
The relationship between serum anti-heat shock protein (Hsp)27 antibody and high sensitive C-reactive protein (hs-CRP) levels and indices of cardiac function were investigated in patients undergoing coronary artery bypass grafting (CABG) or heart valve replacement. The changes in anti-Hsp27 antibody titers and hs-CRP levels were compared among patients undergoing off-pump and on-pump CABG or valvular heart replacement. Fifty-three patients underwent off-pump, on-pump CABG, and heart valvular replacement in each group. Serum anti-Hsp27 titers and hs-CRP values were measured 24 h before and after the operation and at discharge. Echocardiography was performed before surgery and before discharge. The results were compared with values from 83 healthy controls. hs-CRP levels increased and anti-Hsp27 antibody decreased following surgery (P < 0.001 and P < 0.05, respectively), although these changes were independent of operative procedure (P = 0.361 and P = 0.120, respectively). Anti-Hsp27 antibody levels were higher at the time of discharge (P = 0.016). Only in coronary patients were anti-Hsp27 antibody levels negatively associated with E/E′ (r = −0.268, P = 0.022), a marker of pulmonary capillary wedge pressure. In conclusions, anti-Hsp27 antibody levels are associated with indices of cardiac function in coronary patients. Cardiopulmonary bypass had no significant effect on the induction of changes in anti-Hsp27 levels. Moreover, anti-Hsp27 antibody levels fell in all groups postoperatively; this may be due to the formation of immune complexes of antigen–antibody, and antibody levels were higher at the time of discharge.
Electronic supplementary material
The online version of this article (doi:10.1007/s12192-012-0358-y) contains supplementary material, which is available to authorized users. 相似文献10.
Noushin Saljoughian Tahereh Taheri Farnaz Zahedifard Yasaman Taslimi Fatemeh Doustdari Azam Bolhassani Delaram Doroud Hiva Azizi Kazem Heidari Mohammad Vasei Nabiollah Namvar Asl Barbara Papadopoulou Sima Rafati 《PLoS neglected tropical diseases》2013,7(4)
Visceral leishmaniasis (VL) is a vector-borne disease affecting humans and domestic animals that constitutes a serious public health problem in many countries. Although many antigens have been examined so far as protein- or DNA-based vaccines, none of them conferred complete long-term protection. The use of the lizard non-pathogenic to humans Leishmania (L.) tarentolae species as a live vaccine vector to deliver specific Leishmania antigens is a recent approach that needs to be explored further. In this study, we evaluated the effectiveness of live vaccination in protecting BALB/c mice against L. infantum infection using prime-boost regimens, namely Live/Live and DNA/Live. As a live vaccine, we used recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinases (CPA and CPB without its unusual C-terminal extension (CPB-CTE)) as a tri-fusion gene. For DNA priming, the tri-fusion gene was encoded in pcDNA formulated with cationic solid lipid nanoparticles (cSLN) acting as an adjuvant. At different time points post-challenge, parasite burden and histopathological changes as well as humoral and cellular immune responses were assessed. Our results showed that immunization with both prime-boost A2-CPA-CPB-CTE-recombinant L. tarentolae protects BALB/c mice against L. infantum challenge. This protective immunity is associated with a Th1-type immune response due to high levels of IFN-γ production prior and after challenge and with lower levels of IL-10 production after challenge, leading to a significantly higher IFN-γ/IL-10 ratio compared to the control groups. Moreover, this immunization elicited high IgG1 and IgG2a humoral immune responses. Protection in mice was also correlated with a high nitric oxide production and low parasite burden. Altogether, these results indicate the promise of the A2-CPA-CPB-CTE-recombinant L. tarentolae as a safe live vaccine candidate against VL. 相似文献