Research progress on anhedonia and its measurement methods / 中国药理学通报

Anhedonia, or markedly diminished interest or pleas-ure, is a hallmark symptom of depression.As a psychopathological symptom, anhedonia was first noted in the early 19th century.The neurobiological mechanisms that underline anhedonia and its role in diagnosing depression disorder or evaluating antidepressant response have long been aroused attention for nearly a century.Consequently, there are many measuring methods established in both the animal study and human research, which would be reviewed in the present study.

The proteomics research of 4-amino-2-trifluoromethyl-phenyl retinate on human leukemia K562 cells / 中国药理学通报

Aim To explore the proteomics mechanism of the differentiation induction effect of 4-amino-2-trif-luoromethyl-phenyl retinate(ATPR)on human leukemi-a K562 cells. Methods Human leukemia K562 cells were incubated with the same concentration (1 × 10 - 6 mol·L - 1 ) of ATPR or ATRA for 48 hours. The total cell proteins were collected, purified and digested by trypsin, solid phase extraction, and the peptides were detected by ESI-LC-MS / MS. The difference of the pro-tein expression between the cells treated with ATPR and ATRA was compared by using the Discoverer Pro-teome 1. 2 software, and the molecular function, the biological process and other information of those pro-teins were analyzed based on the DAVID, KEGG, STRING databases. Results 120 specific proteins were identified only in the ATPR group, 143 only in the ATRA group, and 422 other proteins in both groups. Results of DAVID analysis showed that ATPR-induced specific proteins were mainly involved in 39 biological processes of proteins and macromolecules metabolism, protein transport and localization and so on. Results of KEGG analysis revealed that ATPR-in-duced proteins participated in signal pathways, mainly metabolic pathways, PI3K-Akt signal pathway, TGF-beta signal pathway and other pathways in cancer. String protein interaction network analysis displayed that ATPR-induced proteins, like EIF3A, EIF6, RPL3, RPL8, RPL13, RPL7A, RPL21, RPS3, RPS14, NACA, BTF3, NHP2L1, PPP2CA proteins had direct interactions with more than or equal to 10 associated proteins. Conclusion The differentiation induction effect of ATPR on K562 cells might be as-cribed to the ATPR-induced proteins interaction net-work and the specific central proteins it induced, which are involved in the regulation of cell prolifera-tion, differentiation and apoptosis.

Effects of extracellular acidosis on pyroptosis of rat articular chondrocytes and its possible mechanisms / 中国药理学通报

Aim To study the effects of extracellular acidosis on articular chondrocytes pyroptosis and its possible mechanisms. Methods Primary articular chondrocytes were incubated in different pH and NAC. The expression of proinflammatory cytokines IL-1β, IL-18, ASC, NLRP3, caspase-1 were detected by Western blot and real-time PCR. The state of pyropto-sis was identified by AO/EB staining and LDH con-tents. The expression of ROS was observed by DCFH-DA, and ELISA was used to detect the IL-1β,IL-18 in cultured supernatants. Results Compared with the normal cell, extracellular acidosis could increase the expression of IL-1β, IL-18, ASC, NLRP3 and caspase-1 , upregulate the fluorescence intensity of in-tercellular ROS, accompanied with the promoted release of LDH. Moreover, it is observed that extra-cellular acidosis could also induce chondrocytes death by AO/EB staining. NAC,the scavenger of ROS could inhibit these effects of extracellular acidosis on chon-drocytes. Conclusion Extracellular acidosis may in-duce chondrocyte pyroptosis via upregulating the intra-cellular ROS content.

Advances in studies on role of Nesfatin-1 in depression / 中国药理学通报

Nesfatin-1, discovered in 2006 by Oh-I as an 82-ami-no-acid peptide derived from the precursor protein nucleobindin2 (NUCB2), has been identified to play an important role in the regulation of food intake and energy metabolism. Recently, it has also been found that Nesfatin-1 might be associated with the pathogenesis of depression. This article reviewed the advances in related studies on Nesfatin-1 at home and abroad, which should throw light in expliciting the physiological function of Nesfatin-1 and understanding the neurobiological mechanism of depression.

Inducing effect of 4-Amino-2-Trifluoromethyl-Phenyl Retinate on differentiation of human breast cancer MDA-MB-231 cell and its possible mechanisms / 中国药理学通报

Aim To investigate the effect of 4-Amino- 2-Trifluoromethyl-Phenyl Retinate on human breast cancer cells MDA-MB-231 and the possible mecha-nisms. Method Human breast cancer MDA-MB-231 cells were incubated with different concentrations of ATPR in vitro. MTT assay was performed to measure the proliferation of MDA-MB-231 . Cell growth curves were made by counting cells and morphologic changes were observed by Wright-Giemsa staining. The differ-entiation marker mucin-1 ( MUC-1 ) was measured by enzyme linked immunosorbent assay ( ELISA ) . Cell cycle was examined by Flow cytometry ( FCM ) . The expression of retinoic acid receptors ( RARs) and reti-noid X receptors ( RXRs ) were detected by Western blot and Quantitative real-time PCR (q-RT-PCR),re-spectively. Results Compared with solvent group, ATPR could inhibit the proliferation of MDA-MB-231 cells in a time-and dose dependent manner and induce the maturing and normality of morphology. The express of MUC-1 was significantly decreased, and the progres of cell cycle was blocked in the G0/G1-phase. The ex-pression of RARγ was decreased. Conclusions AT-PR could inhibit proliferation and induce differention of MDA-MB-231cells, it′s associated with RARγ.

Effects of BAPTA-AM on acid-induced autophagy of rat articular chondrocytes and its possible mechanisms / 中国药理学通报

Aim To observe the effect of BAPTA-AM on extracellular acid-induced autophagy in rat articular chondrocytes and its possible mechanisms.Methods Rat articular chondrocytes were isolated from Sprague-Dawley rats and incubated with different pH medium. The states of autophagy were examined by acridine or-ange (AO ) staining .Moreover,the expressions of LC3 ,Beclin-1 ,ULK1 ,CaMKKβ,AMPK and mTOR were detected using Western blot or quantitative real-time PCR (qRT-PCR ). Intracellular calcium ([Ca2+]i )was analyzed by a Ca2+-imaging method. Results Compared with pH 6.0 group,BAPTA-AM could significantly decrease the activation of autophagyinduced by acid exposure,and the expressions of autophagy markers including LC3 Ⅱ,Beclin1 and ULK1were also decreased,accompanied with reduced acidinduced [Ca2 +]i influx,decreased proteins expressionof CaMKKβand phosphorylatedAMPK,and increasedphosphorylation of mTOR.Conclusion BAPTAAMcan significantly restrain acidinduced autophagy in ratarticular chondrocytes,the mechanism of which may beassociated with decreased Ca2 + influx.

Role of acid-sensing ion channel 1 a in matrix turnover and MAPK expression of articular chondrocytes of rats / 中国药理学通报

Aim TostudytheroleofASIC1aonthe matrix turnover and MAPK expression of the rat articu-lar chondrocytes with extracellular acidosis. Methods ArticularchondrocyteswereisolatedfromSprague-Dawley rats, and their phenotype was determined by toluidine blue and immunocytochemical staining. The GAG content of cell culture supernatant was deter-mined by dimethyl-methylene blue spectrophotometric assay, while Hyp content by chloramine T assay. ELISA assay was used to measure MMP-2 , TIMP-2 content. Furthermore, the ERK1/2, p38 MAPK phos-phorylation protein expression levels were tested by Westernblotassay.Results ASIC1acontributedto the effect of GAG, Hyp and TIMP-2 levels reduction induced by extracellular acidification, while the effect of MMP-2 was weaker. Moreover, ASIC1a could in-crease the ERK1/2 , p38 MAPK phosphorylation pro-teinexpressionlevels.Conclusion ASIC1acould regulate rat articular chondrocytes matrix turnover via ERK1/2 and p38 MAPK signaling pathway, and there-by inhibit the rat articular cartilage damage induced by acidosis.

Tissue distribution on a novel derivate of all-trans-retinoic acid,ATPR / 中国药理学通报

Aim To develop a sensitive,specific and accurate method for quantifying a novel derivate of all-trans-retinoic acid, 4-amino-2-trifluoromethyl-phenyl retinate (ATPR)in rat tissues to investigate the tissue distribution of ATPR in rats.Methods Sprague-Daw-ley (SD)rats were killed by exsanguination at 2,4,7 h after a single intragastric administration with one dose of ATPR (20 mg·kg-1 )or at 5 min,1 h,5 h after a single intravenous administration with one dose of AT-PR (7 mg·kg-1 ).The concentration of ATPR in the tissues was determined by high performance liquid chromatography (HPLC)method.Results After the rats were administrated intragastrically, the highest concentration of ATPR was observed in intestine,fol-lowed by liver,spleen and lung,while the distribution in heart,kidney,fat and brain was very little.Howev-er,the highest concentration of ATPR was in liver after given intravenously,followed by spleen and lung,and very low in heart,kidney,intestines,fat and brain. Conclusion The distribution of ATPR is higher in liv-er after administrated both intragastrically and intrave-nously,suggesting the potential anti-proliferation and differentiation inducing effects of ATPR targeting at liv-er cancer.

Study on the bioequivalence of gliclazide sustained released tablet in healthy volunteers / 中国药理学通报

Aim To evaluate the bioequivalence of two preparations of gliclazide in healthy volunteers.Methods The concentration of gliclazide was measured by high performance liquid chromatography(HPLC) after a single or multiple dosage of gliclazide sustained released tablet in healthy volunteers.The pharmacokinetic parameters of the two preparations were calculated by 3P97 program.LnAUC0~∞,lnAUC0~72 and lnAUC0~? were used to evaluate the bioequivalence of the two preparations with analysis of variance and two one-side t-test.Results Both the gliclazide extended action tablet were best fitted to one-compartment model.The main parameters of the tested and reference gliclazide after a single dose were as follows:Cmax(2.07?0.61) and(2.26?0.61)mg?L-1;Tmax(5.10?0.55)h and(5.05?0.51)h;T12Ka(1.50?0.26)h and(1.52?0.27)h;T12Ke(8.89?1.56)h and(8.68?1.72)h;MRT(22.63?1.01)h and(22.38?0.93)h;AUC0~72(39.19?8.03)mg?h-1?L-1 and(39.26?8.37)mg?h-1?L-1;AUC0~∞:(45.80?9.51)mg?h-1?L-1 and(45.57?9.76)mg?h-1?L-1;F0~72 and F0~∞(100.19?6.22)% and(100.85?5.88)%,respectively.The main parameters of the tested and reference gliclazide after multiple dose were as follows:Cmax(4.83?0.86)mg?L-1 and(4.69?0.64)mg?L-1;Cmin(0.68?0.14) mg?L-1 and(0.66?0.12)mg?L-1;Tmax:(4.10?0.45) h and(4.10?0.55)h;T12Ka:(2.03?0.53)h and(2.04?0.40)h;T12Ke:(7.24?0.87)h and(7.09?1.14)h;MRT(9.17?0.30)h and(9.19?0.37)h;AUCSS:(41.62?6.48) mg?h-1?L-1 and(42.18?6.03)mg?h-1?L-1;Cav:(1.73?0.27)mg?L-1 and(1.76?0.25)mg?L-1;DF(240.85%?34.07)and(230.23%?24.80%) respectively.The relative bioavailability was(98.60?4.60)%.The AUC0~T,AUC0~∞ or AUCSS,Cmax and Tmax were bioequivalent between the two preparations.Conclusion The tested and reference gliclazide sustained released tablet are bioequivalent.