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Antipsychotic drugs have various neuropharmacological properties as a result of their structural diversity. Despite their therapeutic benefits, most of the prescribed atypical antipsychotics can induce severe side effects, including weight gain, type II diabetes mellitus, and cardiovascular diseases. Among the developed atypical antipsychotic agents, tetracyclic dibenzodiazepine and thienobenzodiazepine compounds, particularly clozapine and olanzapine, are associated with the greatest weight gain and metabolic disturbances. However, the unique chemical structure of these compounds causes the low risk of side effects reported for typical antipsychotics (e.g. extrapyramidal symptoms and tardive dyskinesia). This report reviews the recent discovery of the potential role of the chemical structure of antipsychotics in their therapeutic properties and metabolic disturbances. By developing structure-activity relationship studies for atypical antipsychotics, we will improve our understanding of the structural modifications of these chemical classes that lead to reduced weight gain, which will be an invaluable step toward the discovery of the next generation of atypical antipsychotics. In this review, we suggest that a novel dibenzodiazepine or thienobenzodiazepine antipsychotic drug with lower affinity for H(1) receptors may significantly advance schizophrenia therapy. 相似文献
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Arezoo Rajabian Hamid Reza Sadeghnia Azar Hosseini Seyed Hadi Mousavi Mohammad Taher Boroushaki 《Journal of cellular biochemistry》2020,121(2):1778-1789
3-Acetyl-11-keto-β-boswellic acid (AKBA), a pentacyclic triterpenic acid present in gum resin of Boswellia serrata, has been found to possess antioxidant and neuroprotective properties. In this study, we aimed to examine protective properties of AKBA against glutamate-induced neuronal injury. To investigate the effects of AKBA (2.5-10 µM) on glutamate injury in neuron-like cells PC12 and N2a, two treatment regimens (incubation for 2 or 0 hours before glutamate exposure) were used. Then, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method was used to determine viability of the cells. Cellular redox status was evaluated using fluorimetry and comet assays. Annexin V/propidium iodide double staining and Western blot analysis of relative apoptotic proteins were conducted. Based on the results, 24 hours incubation with glutamate (8 mM) increased the cell mortality of PC12 and N2a (P < .001). However, AKBA (2.5-10 µM) enhanced the cell viability in both treatment regimens (P < .001). Also co- and pretreatment with AKBA significantly attenuated lipid peroxidation, reactive oxygen species production, and DNA injury (P < .05 and P < .001). AKBA also restored the activity of cellular superoxide dismutase under glutamate toxicity; this effect was seen to be more significant during the pretreatment regimen (P < .001). Moreover, Western blot analysis indicated that AKBA inhibited glutamate-induced programmed cell death through depressing the elevation of the expression ratio of Bax/Bcl-2 and cleaved-caspase-3 proteins, concentration-dependently. Overall, the present findings suggest the neuroprotective activities of AKBA against glutamate-induced cell injury probably by inhibiting oxidative damage and reducing apoptotic cell death. 相似文献
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Osei Yaw Ampomah Seyed Abdollah Mousavi Kristina Lindström Kerstin Huss-Danell 《Systematic and applied microbiology》2017,40(1):51-58
Rhizobia nodulating native Astragalus and Oxytropis spp. in Northern Europe are not well-studied. In this study, we isolated bacteria from nodules of four Astragalus spp. and two Oxytropis spp. from the arctic and subarctic regions of Sweden and Russia. The phylogenetic analyses were performed by using sequences of three housekeeping genes (16S rRNA, rpoB and recA) and two accessory genes (nodC and nifH). The results of our multilocus sequence analysis (MLSA) of the three housekeeping genes tree showed that all the 13 isolates belonged to the genus Mesorhizobium and were positioned in six clades. Our concatenated housekeeping gene tree also suggested that the isolates nodulating Astragalus inopinatus, Astragalus frigidus, Astragalus alpinus ssp. alpinus and Oxytropis revoluta might be designated as four new Mesorhizobium species. The 13 isolates were grouped in three clades in the nodC and nifH trees. 15N analysis suggested that the legumes in association with these isolates were actively fixing nitrogen. 相似文献
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Bordbar AK Taheri-Kafrani A Mousavi SH Haertlé T 《Archives of biochemistry and biophysics》2008,470(2):103-110
The heat capacity changes for interaction of human serum albumin (HSA) and a cationic surfactant—cetylpyridinium chloride (CPC), were studied at conditions close to physiological (50 mM HEPES or phosphate buffer, pH 7.4 and 160 mM NaCl) carrying out isothermal calorimetric titrations (ITC) at various temperatures (20-40 °C). ITC measurements indicated that the small endothermic changes associated with CPC demicellization were temperature independent at these conditions. Surprisingly, important enthalpy changes associated with binding of CPC to HSA were exothermic and temperature independent at lower concentrations (below 0.022 mM) of CPC and endothermic and temperature dependent at higher concentrations of CPC. The values of heat capacity changes were obtained for each studied concentration of CPC from the plot of enthalpy changes vs temperature. The obtained results demonstrate the temperature independence of heat capacity changes at entire range of studied CPC concentrations. Both enthalpograms and heat capacity curves indicate the two-step mechanism of HSA folding changes due to its interactions with CPC. The first step corresponds to transition from native state to partially unfolded state and the second to unfolding and to the loss of tertiary structure. The analysis of the results indicates that predominant cooperative unfolding occurs at CPC/HSA molar ratio region between 25 and 30. Such information could not be extracted from thermograms and describes the role of heat capacity as a major thermodynamic quantity giving insight on physical, mechanistic and even atomic-level into how HSA may unfold and interact with CPC. The effect of CPC binding on HSA intrinsic fluorescence, UV-Vis and CD spectra were also examined. Hence, the analysis of spectral data confirms the ITC results about the biphasic mechanism of HSA folding changes induced by CPC. The CD measurement also represents the conservation of considerable secondary structure of HSA due to interaction with CPC. 相似文献
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S. Jamaleddin Mousavi Stéphane Avril 《Biomechanics and modeling in mechanobiology》2017,16(5):1765-1777
It is now a rather common approach to perform patient-specific stress analyses of arterial walls using finite-element models reconstructed from gated medical images. However, this requires to compute for every Gauss point the deformation gradient between the current configuration and a stress-free reference configuration. It is technically difficult to define such a reference configuration, and there is actually no guarantee that a stress-free configuration is physically attainable due to the presence of internal stresses in unloaded soft tissues. An alternative framework was proposed by Bellini et al. (Ann Biomed Eng 42(3):488–502, 2014). It consists of computing the deformation gradients between the current configuration and a prestressed reference configuration. We present here the first finite-element results based on this concept using the Abaqus software. The reference configuration is set arbitrarily to the in vivo average geometry of the artery, which is obtained from gated medical images and is assumed to be mechanobiologically homeostatic. For every Gauss point, the stress is split additively into the contributions of each individual load-bearing constituent of the tissue, namely elastin, collagen, smooth muscle cells. Each constituent is assigned an independent prestretch in the reference configuration, named the deposition stretch. The outstanding advantage of the present approach is that it simultaneously computes the in situ stresses existing in the reference configuration and predicts the residual stresses that occur after removing the different loadings applied onto the artery (pressure and axial load). As a proof of concept, we applied it on an ideal thick-wall cylinder and showed that the obtained results were consistent with corresponding experimental and analytical results of the well-known literature. In addition, we developed a patient-specific model of a human ascending thoracic aneurysmal aorta and demonstrated the utility in predicting the wall stress distribution in vivo under the effects of physiological pressure. Finally, we simulated the whole process preceding traditional in vitro uniaxial tensile testing of arteries, including excision from the body, radial cutting, flattening and subsequent tensile loading, showing how this process may impact the final mechanical properties derived from these in vitro tests. 相似文献