1.Prospects for histone deacetylase inhibitors as antidepressants
Kai-yun YAO ; Hong-wan DING ; Lin-yu CAO ; Yin-ge GAO ; Jian-jun ZHANG ; Gui-bin WANG
Acta Pharmaceutica Sinica 2021;56(1):29-36
Depression is a serious mental illness with a high incidence. At present, we do not fully understand the specific pathological mechanisms of depression, and the efficacy of drug treatments is very limited. Recent studies have shown that epigenetic changes that occur in specific brain regions may be a key mechanism by which environmental factors to interact with individuals to influence the risk of depression. Therefore, drugs that target epigenetic regulation may become a new direction for the development of antidepressants. Histone deacetylase inhibitors (HDACi) are a class of compounds that inhibit histone deacetylase activity, which has been reported to be associated with depression; this article addresses the use of HDACi in preclinical studies, and their potential therapeutic role and limitations of use in depression.
2.Modeling and implementation method for the automatic biochemistry analyzer control system.
Dong WANG ; Wan-cheng GE ; Chun-lin SONG ; Yun-guang WANG
Chinese Journal of Medical Instrumentation 2009;33(3):217-220
In this paper the system structure The automatic biochemistry analyzer is a necessary instrument for clinical diagnostics. First of is analyzed. The system problems description and the fundamental principles for dispatch are brought forward. Then this text puts emphasis on the modeling for the automatic biochemistry analyzer control system. The objects model and the communications model are put forward. Finally, the implementation method is designed. It indicates that the system based on the model has good performance.
Autoanalysis
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instrumentation
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methods
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Biochemistry
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instrumentation
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methods
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Equipment Design
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Models, Theoretical
3.Real-time quantitative PCR detecting B7-H1 gene expression in leukemia cells and its clinical implications.
Xin LI ; Ya-fei WANG ; Wei GE ; Zeng-jun LI ; Zhen YU ; Yun-tao LI ; Chang-chun WAN ; Qiao-chuan LI ; Lu-gui QIU
Chinese Journal of Hematology 2007;28(12):837-840
OBJECTIVETo detect the expression of B7-H1 gene in bone marrow mononuclear cells (BMMNCs) from leukemia patients and explore its clinical implications.
METHODSThe B7-H1 mRNA expression levels of BMMNCs from 74 newly diagnosed leukemia patients and 10 normal volunteers were detected by real-time quantitative PCR. At the same time, BMMNCs from 12 patients in complete remission (CR) after chemotherapy and 5 in relapse were followed up. The correlation between the clinical features of 74 de novo leukemia patients and the expression level of B7-H1 gene was analyzed.
RESULTSThe mRNA expression level of B7-H1 gene in BMMNCs from de novo leukemia patients (RQ = 0.125) was lower than that from normal control (RQ=1). When patients achieved CR the gene expression level (RQ = 69.07) was significantly higher than that before CR (P = 0.001). After relapsed, its level (RQ=4) was still higher than that before CR (P > 0.05). No clinical parameters such as gender, age, peripheral white blood count, blast cells ratio in BM, CD34 positive cells were significantly correlated with the expression level of B7-H1 except the response to therapy. The initial expression level of B7-H1 gene in non CR patients after therapy was significantly higher than that in CR patients (RQ = 26. 91, P = 0.005).
CONCLUSIONThe mRNA expression level of B7-H1 gene in newly diagnosed leukemia patients is lower than that in normal controls, and is higher in CR patients than in newly diagnosed patients. There is a correlation between the gene expression level and responsiveness to therapy.
Adult ; Antigens, CD ; metabolism ; B7-H1 Antigen ; Female ; Humans ; Leukemia ; drug therapy ; genetics ; metabolism ; Male ; Middle Aged ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction
4.Clinical efficacy and safety of lornoxicam vs tramadol patient controlled analgesia in hepatocellular carcinoma patients treated with surgery
Sheng-Lin PEI ; Lin RUAN ; Ling-Hui PAN ; Bing HUANG ; Yu HUANG ; Wan-Yun GE
The Chinese Journal of Clinical Pharmacology 2015;(10):799-801
Objective To evaluate the analgesia effect of lornoxicam versus tramadol patient controlled analgesia in hepatocellular carcinoma patients treated with surgery .Methods A total of 54 hepatocellular car-cinoma patients who were scheduled for operation were included , 28 pa-tients received lornoxicam patients controlled analgesia with lornoxicam 96 mg+0.9% NaCl up to 150 mL.And 26 patients received tramadol patients controlled analgesia with tramadol 96 mg+0.9%NaCl up to 150 mL.The visual analogue scale ( VAS ) and bruggrmann comfort scale (BCS) were recorded in the time point of 4,12,24 and 48 h.The adverse event such as nausea , vomiting and dizziness were compared between the two groups.Results The VAS and BCS had no statistical difference between the two group in each of the time points ( P>0.05 ) . The adverse event incidence were 14.3% and 19.2% in the lornoxicam and tramadol group respectively with no statistical difference ( P>0.05 ) . Conclusion Both lornoxicam versus tramadol were effective in patient con-trolled analgesia for hepatocellular carcinoma patients treated with surgery .
5.Related factors affecting the isolation of multipotent non-hematopoietic adult stem cells from umbilical cord blood.
Yun-Tao LI ; Yan XU ; Hen-Xing MENG ; Wei GE ; Qiao-Chuan LI ; Chang-Chun WAN ; Zhen YU ; Chang-Hong LI ; Lu-Gui QIU
Journal of Experimental Hematology 2006;14(4):731-736
To investigate the related factors affecting the isolation of multipotent non-hematopoietic adult stem cells (MNASCs) from human umbilical cord blood in low serum (2%) condition, the isolation conditions were optimized and the yield of MNASCs was improved. MNASCs from human umbilical cord blood samples were isolated, and the effects of medium component, medium exchange time and initial plating density for isolation of MNASCs were studied. Then, the MNASCs were isolated and cultured in optimal condition, the surface antigen expression and differentiation potential of MNASCs were detected. The result showed that the medium of DMEM/F12 was better than IMDM and DMEM-LG for MNASCs culture in low serum condition. The optimal yield of MNASCs was obtained when mononuclear cells were cultured at a initial plating density of 1 x 10(6) cells/cm2 and the medium was exchanged to remove the nonadherent cells after 72 hours of inoculation. MNASCs isolated and cultured under the above-mentioned conditions maintained a homogenous morphology, high potential ability of expansion and differentiation. It is concluded that culture conditions with low serum defined in this study is optimal for the successful isolation and expansion of umbilical cord blood MNASCs with high numbers for subsequent cellular therapeutic approaches.
Cell Culture Techniques
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methods
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Cell Differentiation
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physiology
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Cell Separation
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methods
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Embryonic Stem Cells
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cytology
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physiology
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Fetal Blood
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cytology
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Humans
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Multipotent Stem Cells
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cytology
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physiology
6.Effects of stromal cell-derived factor 1 and platelet factor 4 on the adhesion characteristics and chemotactic function of ex vivo expanded umbilical cord blood CD34+ cells.
Qiao-Chuan LI ; Yun-Tao LI ; Heng-Xing MENG ; Ya-Fei WANG ; Chang-Chun WAN ; Xin LI ; Wei GE ; Qian LI ; Jun-Ling HAN ; Lu-Gui QIU
Journal of Experimental Hematology 2006;14(1):83-88
To investigate the effects of stromal cell-derived factor 1 (SDF-1) and platelet factor 4 (PF4) on the homing-related function of expanded ex vivo umbilical cord blood CD34(+) cells, purified cord blood CD34(+) cells were cultured in serum-free medium containing a HGF combination of FL + SCF + TPO (FST) with either 100 ng/ml SDF-1 alone, 100 ng/ml PF4 alone, or both of these 2 cytokines. The expansion rate of CD34(+) cells, colony formation, homing-related functions including expression of homing-related adhesion molecules of expanded CD34(+) cell, adhesion activity and chemotactic function of the re-selected expanded CD34(+) cells were evaluated at different time points. The results showed that expansion rate of CD34(+) cells and expansion multiple of CFU in SDF-1 groups were higher than those in control. The expression of CD49e on the expanded CD34(+) cells was remarkable up-regulated, in contrast, expression of CXCR-4 on the expanded CD34(+) cells was remarkable down-regulated in SDF-1 groups. The expression of CD49e, CD54 and CXCR-4 on the expanded CD34(+) cells were remarkably up-regulated in the PF4 groups. In all the SDF-1 group, PF4 group and SDF-1 plus PF4 group, the ability of expanded CD34(+) cells adhering to fibronectin layer were higher than those in the control on day 10. Spontaneous migration rate of expanded CD34(+) cells in SDF-1 groups were higher than those in control, while SDF-1-induced migration rate were lower than those in control on day 10. SDF-1-induced migration rate in PF4 groups were higher than those in control on day 10. Spontaneous and SDF-1-induced migration rate of expanded CD34(+) cells in the SDF-1 plus PF4 groups were higher than those in control on day 10. It is concluded that, SDF-1 and PF4 can up-regulate expression of adhesion molecules on expanded CD34(+) cells, and retain the adherent and migration ability of expanded CD34(+) cells, which is helpful for the homing of expanded CD34(+) cells. In short, SDF-1 and PF4 are helpful for the homing-related function of the expanded UCB HSPC.
Antigens, CD34
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blood
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immunology
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Cell Adhesion
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drug effects
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Cells, Cultured
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Chemokine CXCL12
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Chemokines, CXC
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pharmacology
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Chemotaxis
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immunology
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physiology
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Culture Media, Serum-Free
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Fetal Blood
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cytology
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immunology
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Hematopoietic Stem Cells
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cytology
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drug effects
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Humans
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Platelet Factor 4
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pharmacology
7.Comparison of expanding dendritic cells derived from cord blood and mobilized peripheral blood by two-step culture method.
Ya-Fei WANG ; Heng-Xing MENG ; Wei GE ; Zhen YU ; Yun-Tao LI ; Qiao-Chuan LI ; Chang-Chun WAN ; Yan XU ; Xin LI ; Zheng-Jun LI ; Guo-Rong WANG ; Sheng-Guo YOU ; Lu-Gui QIU
Journal of Experimental Hematology 2006;14(6):1163-1167
To compare the expansion efficiency and function of dendritic cells derived from CB-CD34+ cells and MPB-CD34+ cells by using two-step culture method, enriched CB-CD34+ cells or MPB-CD34+ cells with immunoadsorption were primarily cultured in the presence of FL, SCF, TPO, GM-CSF for 10 days, and then further cultured with a combination of GM-CSF, IL-4, TNF-alpha, CD40Ab and PGE2 to induce DC. The DC phenotypes were detected by flow cytometry, the expansion efficiency and cell function were evaluated by mix-lymphocyte reaction (MLR), IL-12 level was detected by using ELISA and the chemotactic function mediated by secondary lymphoid tissue chemokine (SLC) was determined with Transwell plate. The results indicated that after 10 days of expansion, there were no significant difference in the percentage of CD14+CD1a- cells between CB and MPB [(40.48 +/- 16.85)% vs (28.07 +/- 23.19)%, P > 0.05], but the expansion of total cells in CB was higher than that in MPB (388.88 +/- 84.63-fold vs 79.67 +/- 10.32-fold, P < 0.01), so the yield of CD14+CD1a- cells from CB was significantly higher than that from MPB too (189.42 +/- 25.02-fold vs 28.74 +/- 23.27-fold, P < 0.01). The percentage of CD83+ DCs cultured with CD40Ab/PGE2 derived from CB were higher than those cultured with TNF-alpha derived from MPB respectively [(34.52 +/- 11.22)% vs (3.70 +/- 2.27)% and (36.69 +/- 13.36)% vs (7.34 +/- 3.364)% respectively, P < 0.01]. In the same circumstance, the yield of CD83+ DCs derived from CB was much more than that from MPB (198.72 +/- 117.53 times vs 33.95 +/- 6.19 times, P < 0.01). There were no difference in stimulating capacity, IL-12 secretion and migration capacity between DCs derived from CB and MPB. It is concluded that DCs induced from CB-CD34+ cells by two-step culture possess similar functions with that from MPB-CD34+ cells, but the yield of DCs from CB CD34+ cells is much more than that from MPB CD34+ cells.
Antigens, CD34
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analysis
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Cell Culture Techniques
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methods
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Cell Proliferation
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Cell Separation
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Cells, Cultured
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Dendritic Cells
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cytology
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immunology
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Fetal Blood
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cytology
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Hematopoietic Stem Cell Mobilization
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Humans
8.Treatment of super obesity by laparoscopic Roux-en-Y gastric bypass: experience of 42 cases.
Jing-ge YANG ; Cun-chuan WANG ; You-zhu HU ; Jin-yi LI ; Jing HUANG ; Yun-long PAN ; Hua YANG ; Jun-liang GAN ; Wan-ling LIU ; Guo CAO ; Zhi-lun LI ; Ning REN
Chinese Journal of Gastrointestinal Surgery 2012;15(11):1115-1119
OBJECTIVETo investigate the feasibility and efficacy of laparoscopic Roux-en-Y gastric bypass(LRYGB) for super obesity(BMI≥50 kg/m(2)).
METHODClinical data of 42 patients undergoing LRYGB in the First Affiliated Hospital of Jinan University between 2004 and 2008 were analyzed retrospectively.
RESULTSAll the LRYGB procedures were successfully performed with no conversion to open surgery. Average operation time was 145.1 minutes, volume of blood loss during the surgery was 25.0 ml, and length of postoperative hospital stay was 9.9 days. The cases were followed up for 1 month to 30 months. Body weight and BMI decreased significantly 1 month after the operation and reached a minimum level after 2 years then became stable while excess body weight loss rate(EWL) increased(P<0.05). All the obese-related symptoms were relieved significantly. Four cases(9.5%) showed complications during perioperative period including 1 case of respiratory failure, 2 cases of gastrojejunal anastomotic bleeding, 1 case of umbilical wound infection, and 11 developed long-term complications. All of them were cured by conservative treatment.
CONCLUSIONSTreatment of super obesity by LRYGB is feasible with significant short-term results. But due to the difficulty of the operation and postoperative complications, comprehensive treatment from experienced bariatric surgical team is needed. The long-term outcome needs for further observation.
Adolescent ; Adult ; Female ; Gastric Bypass ; methods ; Humans ; Laparoscopy ; Male ; Middle Aged ; Obesity, Morbid ; surgery ; Retrospective Studies ; Treatment Outcome ; Young Adult
9.Quercetin alleviates podocyte injury by inhibiting inflammation and pyroptosis through SIRT1/STAT3/GSDME
Jie-Qiong WANG ; Ge LI ; Shao-Hua WANG ; Yu WAN ; Yun LIU ; Cong-Gai HUANG ; Qu-Lian GUO ; Fang-Fang ZHONG
Chinese Pharmacological Bulletin 2024;40(7):1279-1287
Aim To investigate the effect of quercetin(Que)on podocyte inflammatory injury and the under-lying mechanism.Methods MPC5 cells were divided into normal glucose group(NG),mannitol group(MA),high glucose group(HG)and high glucose+quercetin group(HG+Que).Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry.The expression of SIRT1,STAT3,apoptosis-related proteins(Bax,Bcl-2,caspase-3)and pyroptosis pro-tein GSDME was detected by Western blot.The ex-pression levels of inflammatory factors(IL-6,TNF-α,IL-18,IL-1β)in cell supernatants were detected by ELISA.Then small interfering RNA technology was used to knockdown SIRT1 expression.To further eval-uate the biological significance of SIRT1 in response to high glucose and Que treatment,negative control group(HG+si-NC+Que)and SIRT1 interference group(HG+si-SIRT1+Que)were added in the presence of high glucose and Que.Results Compared with the high glucose group,40 μmol·L-1 Que could alleviate the apoptosis of MPC5 cells induced by high glucose,decrease the expression of apoptosis related protein Bax and caspase-3,as well as increase the expression of anti-apoptotic protein Bcl-2;ELISA results showed that Que could decrease the expression of TNF-α,IL-6,IL-1 β and IL-18 induced by high glucose.Mechanical-ly,Que could alleviate the inhibitory effect of high glu-cose on the expression of SIRT1,and further decrease the activation of STAT3 and N-GSDME,and inhibit pyroptosis.Compared with the si-NC group,si-SIRT1 group could reverse the protective effect of Que on the high glucose induced inflammatory damage of podo-cytes,the expression of apoptotic proteins Bax and caspase-3 increased,while the expression of anti-apop-totic protein Bcl-2 decreased.At the same time,the levels of inflammatory cytokines TNF-α,IL-6,IL-1 βand IL-18 in supernatants increased,and the expres-sion of STAT3 and N-GSDME increased.Conclusion Que could inhibit pyroptosis and relieve the inflam-matory damage of podocytes through SIRT1/STAT3/GSDME pathway.
10.Mechanism of Huanglian Wendan Decoction in improving impaired glucose tolerance based on skeletal muscle NLRP3/caspase-1/IL-1β, IL-18 pathway.
Wan-Ru DONG ; Han LI ; Yun-Feng LI ; Ning WANG ; Bo-Yan MA ; Ge-Ling LU ; Xiang-Ru XIN ; Bing-Bing CHEN
China Journal of Chinese Materia Medica 2021;46(17):4480-4487
This study investigated the mechanism of improving impaired glucose tolerance(IGT) of rats by Huanglian Wendan Decoction from the perspective of the skeletal muscle Nod-like receptor protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/interleukin-1β(IL-1β), interleukin-18(IL-18) pathway. Healthy male SD rats were fed with the diet containing 45% fat for 20 weeks, accompanied by a high-temperature and high-humidity environment and an inactive lifestyle, for the establishment of the IGT rat model. The rats were divided into the blank control group, model control group, metformin hydrochloride group(positive drug group, 0.05 g·kg~(-1)·d~(-1)) and Huanglian Wendan Decoction group(7.8 g·kg~(-1)·d~(-1)). After continuous intragastric administration for 4 weeks, the obesity and glycemic indexes of all the rats were measured. The fasting serum insulin(FINS) level was determined by ELISA, with the insulin sensitivity index(ISI) and insulin resistance index(IRI) calculated. The mRNA and protein expression le-vels of nuclear factor kappaB(NF-κB), NLRP3, caspase-1, IL-1β and IL-18 in skeletal muscle tissue were detected by real-time polymerase chain reaction(PCR), Western blot and immunofluorescence. Compared with the blank control group, the model control group witnessed significantly increased mRNA and protein expression of NF-κB, NLRP3, caspase-1, IL-1β and IL-18. As revealed by the comparison with the model control group, Huanglian Wendan Decoction could effectively regulate the obesity status, reduce body weight, correct the abnormal levels of 2-hour plasma glucose(2 hPG), insulin resistance index(IRI), insulin sensitivity index(ISI), and lower the mRNA and protein expression of NF-κB, NLRP3, caspase-1, IL-1β and IL-18 in the skeletal muscle tissue of IGT rats. Combined with previous studies, the above results showed that the occurrence and development of IGT was closely related to inflammatory response and the classic pyroptosis pathway in skeletal muscle, such as NLRP3/caspase-1/IL-1β, IL-18. It is inferred that the mechanism of Huanglian Wendan Decoction was to alleviate insulin resistance(IR) and then reverse the course of IGT lies in the regulation of the abnormal insulin receptor signaling pathway based on the NLRP3 inflammasome pathway.
Animals
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Caspase 1/genetics*
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Drugs, Chinese Herbal
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Glucose Intolerance
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Interleukin-18/genetics*
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Interleukin-1beta
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Male
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Muscle, Skeletal
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NF-kappa B/genetics*
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NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
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Rats
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Rats, Sprague-Dawley