1.Mechanism of Danzhi Jiangtang capsule protecting mitochondrial function and reducing vascular calcification via LncRNA TUG1/β-catenin signaling pathway
Ying-Qun NI ; Yi-Xuan LIN ; Si-Hai WANG ; Qin LU ; Jin-Zhi LUO ; Chun-Qin WU ; ZHAO-Hui FANG
Chinese Pharmacological Bulletin 2024;40(5):899-906
Aim To explore how Danzhi Jiangtang cap-sules(DJC)safeguard the mitochondrial activity of vascular smooth muscle cells(VSMCs)by controlling the LncRNA TUG1/β-catenin signaling pathway to de-crease vascular calcification(VC).Methods Vascu-lar smooth muscle cell calcification models were in-duced with β-glycerin and diabetic vascular calcifica-tion rat models were induced with vitamin D3+high-fat diet.Von Kossa staining was applied to detect cal-cification of cells and vascular tissue.Colorimetric method of phthalein complex was used to determine calcium content.P-nitrobenzene phosphate colorimetry was employed to assess alkaline phosphatase(ALP)activity.RT-qPCR was used to analyze the expression of VSMCs'osteoblast transformation related genes bone morphogenetic protein2(BMP2),smooth muscle actin alpha(α-SMA),taurine up-regulated1,LncRNA Tug1(Lnc-RNA TUG1),and β-catenin.Western blotting was utilized to detect the protein expression of BMP2,α-SMA and β-catenin.The mitochondrial membrane potential was detected by JC-1 fluorescence probe.Mitochondrial structure was observed by trans-mission electron microscope.Results DJC reduced LncRNA TUG1 expression,down-regulated β-catenin expression,decreased ALP activity and calcium depo-sition,protected mitochondrial function,restored mem-brane potential,and decreased osteoblastic transforma-tion of VSMCs induced by glycerin phosphate.Impor-tantly,DJC attenuated diabetic lower limb VC by down-regulating the expression of LncRNA TUG1,β-catenin,and elevating the expression of α-SMA.Con-clusions DJC capsules significantly improved VSMCs by protecting mitochondrial function by LncRNA TUG1/β-catenin signaling to reduce VSMCs'osteo-blast transformation.
2.Research progress of non-coding RNAs in regulating endothelial to mesenchymal transition in diseases
Wei QIN ; Zhi-Jie LUO ; Rui-Xue RONG ; Xue-Ying CHEN
Chinese Pharmacological Bulletin 2024;40(7):1215-1221
Endothelial to mesenchymal transition(EndMT)is a process in which endothelial cells lose their endothelial pheno-type and function and gain mesenchymal phenotype and func-tion.During the embryonic period,EndMT is an essential mech-anism for the development of heart valves,pulmonary arteries and aorta.In recent years,numerous studies have shown that EndMT is also involved in the occurrence and development of cardiovascular diseases such as atherosclerosis,cardiac fibrosis,pulmonary hypertension,and cerebrovascular malformation.In addition,EndMT is also an important mechanism of other organ fibrosis and tumors.Non-coding RNAs(ncRNAs)refer to RNAs that are transcribed from the genome but do not translate into proteins.Studies have shown that the abnormal expression of ncRNAs can participate in various diseases by regulating End-MT.Such ncRNAs with regulatory functions mainly include mi-croRNA(miRNA),long non-coding RNA(lncRNA)and cir-cular RNA(circRNA).This review summarizes the molecular mechanisms by which ncRNAs regulate EndMT in various disea-ses,looking forward to the application prospects of ncRNAs in the treatment of EndMT-related diseases.
3.The neuroprotective effect of Wenfei Jiangzhuo formula on vascular dementia model rats based on regulation of mitochondrial homeostasis by PGAM5-Drp1 axis
Ding ZHANG ; Zhi-Han HU ; Chun-Ying SUN ; Xiao-Dong ZHU ; Fang-Cun LI ; Ming-He JIANG ; Hong-Ling QIN ; Wei CHEN ; Yue-Qiang HU
Chinese Pharmacological Bulletin 2024;40(11):2158-2164
Aim To observe the effects of Wenfei Jiangzhuo formula(WFJZF)on rats with vascular de-mentia and investigate its possible mechanism of ac-tion.Methods Thirty-six healthy male SD rats were randomly divided into the sham group,model group,donepezil group,and low-dose,medium-dose and high-dose groups of Wenfei Jiangzhuo formula,with six rats per group.Except for the sham group,the other groups were prepared as VaD models,and each group was gavaged with the corresponding drugs after suc-cessful modeling,and tests were performed after three weeks of treatment.Behavioral,hippocampal CA1 area morphology,neural dendrites and mitochondrial chan-ges were observed in all groups of rats,and phospho-glycerate mutase 5(PGAM5),dynamics-related pro-teins1(Drp1),opticatrophyprotein-1(OPA1),and other proteins were detected in each group.Results Compared with the sham group,rats in the model group and each intervention group had prolonged es-cape latency(P<0.05),a shorter number of travers-als across the platforms(P<0.05),a sparse morphol-ogy of hippocampal neurons,a reduction in the number of secondary dendritic spines,and a rupture of the out-er membrane of the mitochondria;the expression of the PGAM5 and Drp1 proteins in hippocampal tissues was elevated(P<0.05),and the expression of the OPA1 and Mfn1/2 protein expression decreased(P<0.05);compared with the model group,donepezil group and Wenfei Jiangzhuo formula high-dose group of rats had shorter evasion latency(P<0.05),increased number of times to traverse the platform(P<0.05),increased number of hippocampal neurons,tightly packed,more secondary dendritic structures,and reduced mitochon-drial damage;the expression of PGAM5 and Drp1 pro-teins was reduced(P<0.05),and the expression of OPA1 and Mfn1/2 proteins was elevated(P<0.05).Conclusions Wenfei Jiangzhuo formula can regulate the PGAM5-Drp1 signaling axis to improve the balance of mitochondrial homeostasis,thus improving the cog-nitive condition of the brain and exerting cerebroprotec-tive effects.
4.Clinical Characteristics and Survival Analysis of Single Center Adult Chronic Myeloid Leukemia in Chronic Phase
Xia-Xia JIAO ; Yuan-Yuan ZHANG ; Jing PAN ; Lei-Na SONG ; Cai-Qin LIN ; Hui-Zhen SHI ; Bin ZHU ; Su-Li WANG ; Shao-Ying PAN ; Zhi-Yong DING ; Wen-Li ZHAO
Journal of Experimental Hematology 2024;32(5):1381-1387
Objective:To investigate the clinical characteristics and prognosis of single center adult chronic myeloid leukemia in chronic phase(CML-CP).Methods:Clinical data of 41 adult CML-CP patients in Department of Hematology,Shanghai Fengxian District Central Hospital from January 2015 to May 2021 were retrospectively analyzed.The clinical characteristics and prognosis of patients between<60 years group and ≥ 60 years group were compared.Results:The 41 patients included 27(65.9%)males and 14(34.1%)females.The median age of the patients was 56(19-84)years,with 22 cases(53.7%)<60 years and 19 cases(46.3%)≥60 years.Univariate analysis indicated that the proportions of patients with comorbidities,intermediate/high-risk Sokal score,myelofibrosis,and lactate dehydrogenase ≥1 000 U/L were significantly increased in ≥60 years group compared with<60 years group at initial diagnosis(all P<0.05).There were no statistical differences in the distribution of sex,ELST score,white blood cell count,platelet count,peripheral blood basophil percentage,peripheral blood eosinophil percentage and bone marrow primitive cell percentage between the two groups(P>0.05).The proportion of patients taking reduced-dose imatinib in≥60 years group significantly increased(P<0.001).Patients<60 years had a higher proportion of molecular biological remission after treatment of tyrosine kinase inhibitors(TKIs)than patients ≥ 60 years(P<0.001).The incidence of non-hematologic adverse reactions to TKI therapy significantly increased in patients ≥ 60 years(P<0.001).Multivariate analysis showed that no adverse factors affecting the efficacy and prognosis of TKI.Conclusion:Compared with adult CML-CP patients<60 years,patients ≥ 60 years gain fewer benefits from TKI treatment and increased adverse reactions.
5.Causal association between depression and stress urinary incontinence:A two-sample bidirectional Mendelian randomization study
Cheng-Xiao JIANG ; Wei-Qi YIN ; Jing-Jing XU ; Ying-Jiao SHI ; Li WANG ; Zhi-Bo ZHENG ; Rui SU ; Qin-Bo HU ; Jun-Hai QIAN ; Shu-Ben SUN
National Journal of Andrology 2024;30(3):217-223
Objective:To investigate the causal correlation between depression and stress urinary incontinence(SUI)using Mendelian randomization(MR)analysis.Methods:We searched the FinnGen Consortium database for genome-wide association studies(GWAS)on depression and obtained 23 424 case samples and 192 220 control samples,with the GWAS data on SUI provided by the UK Biobank,including 4 340 case samples and 458 670 control samples.We investigated the correlation between depression and SUI based on the depression data collected from the Psychiatric Genomics Consortium(PGC).We employed inverse-variance weighting as the main method for the MR study,and performed sensitivity analysis to verify the accuracy and stability of the findings.Results:Analysis of the data from the UK Biobank and FinnGen Consortium showed that depression was significantly correlated with an increased risk of SUI(P=0.005),but not SUI with the risk of depression(P=0.927).And analysis of the PGC data verified the correlation of depression with the increased risk of SUI(P=0.043).Conclusion:Depression is associated with an increased risk of SUI,while SUI does not increase the risk of depression.
6.Screening of anti-inflammatory activity Q-markers for Glycyrrhizae Radix et Rhizoma
Qin CHEN ; Wen-Hui ZHENG ; Hai-Ying BAI ; Ping-Shun SONG ; Ping-Rong YANG ; Zhi-Gang YANG
Chinese Traditional Patent Medicine 2024;46(9):2841-2850
AIM To screen anti-inflammatory activity Q-markers for Glycyrrhizae Radix et Rhizoma.METHODS Lipopolysaccharide was used for stimulating RAW264.7 macrophages to establish inflammatory model,after which the NO inhibitory rates of different grades of medicinal materials were determined.The UHPLC-QTOF-MS fingerprints were established,after which chemical constituents were identified,heatmap was drawn,and orthogonal partial least squares analysis was performed.RESULTS Grade 1 and grade 2 medicinal materials demonstrated higher NO inhibitory rates than gradeless and uniformly-priced goods(P<0.05,P<0.01).There were 211 common peaks in the fingerprints of 47 batches of medicinal materials,total 56 compounds were identified,containing 17 saponins,6 flavonoids,8 flavanones,4 chalcones,12 isoflavones and 9 other kinds.The relative contents of isoflavones,coumarins,kaempferol and licoflavonol in grade 1 and grade 2 medicinal materials were higher than those in gradeless and uniformly-priced goods,while the relative contents of flavanones,chalcones and saponins in wild products were higher than those in cultivated products.Neoliquiritin,isoliquiritin,kaempferol,hedysarimcoumestan E,licorice saponin C2,licoarylcoumarin,glicoricone and liconeolignan were taken as Q-markers.CONCLUSION This stable and reliable method has a certain reference value for the quality control of Glycyrrhizae Radix et Rhizoma.
7. Influence of quercetin on aging of bone marrow mesenchymal stem cells induced by microgravity
Yu-Tian YANG ; Ying-Ying XUAN ; Yu-Tian YANG ; Ying-Ying XUAN ; Yu-Hai GAO ; Long-Fei WANG ; Han-Qin TANG ; Zhi-Hui MA ; Liang LI ; Yi WU ; Ke-Ming CHEN ; Yu-Tian YANG ; Ying-Ying XUAN ; Yu-Hai GAO ; Long-Fei WANG ; Han-Qin TANG ; Zhi-Hui MA ; Liang LI ; Yi WU ; Ke-Ming CHEN
Chinese Pharmacological Bulletin 2024;40(1):38-45
Aim To investigate the effect of quercetin on the aging model of bone marrow mesenchymal stem cells established under microgravity. Methods Using 3D gyroscope, a aging model of bone marrow mesenchymal stem cells was constructed, and after receiving quercetin and microgravity treatment, the anti-aging effect of the quercetin was evaluated by detecting related proteins and oxidation indexes. Results Compared to the control group, the expressions of age-related proteins p21, pi6, p53 and RB in the microgravity group significantly increased, while the expressions of cyclin D1 and lamin B1 significantly decreased, with statistical significance (P<0.05). In the microgravity group, mitochondrial membrane potential significantly decreased (P<0.05), ROS accumulation significantly increased (P <0.05), SOD content significantly decreased and MDA content significantly increased (P<0.05). Compared to the microgravity group, the expressions of age-related proteins p21, pi6, p53 and RB in the quercetin group significantly decreased, while the expressions of cyclin D1 and lamin B1 significantly increased, with statistical significance (P<0.05). In the quercetin group, mitochondrial membrane potential significantly increased (P<0.05), ROS accumulation significantly decreased (P<0.05), SOD content significantly increased and MDA content significantly decreased (P<0.05). Conclusions Quercetin can resist oxidation, protect mitochondrial function and normal cell cycle, thus delaying the aging of bone marrow mesenchymal stem cells induced by microgravity.
8.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
9.HPLC-MS/MS method for monitoring digoxin in children with small volume of plasma
Zhi-Mei YANG ; Zhang-Ying FENG ; Ya-Bin QIN
The Chinese Journal of Clinical Pharmacology 2024;40(9):1331-1335
Objective To establish a high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method for therapeutic drug monitoring(TDM)of digoxin in children.Methods The plasma samples 10 μL were precipitated protein by acetonitrile.Then,the analytes were gradient eluted on a Phenomenex Kinetex EVO C18 column(30.0 mm × 2.1 mm,2.6 μm)by HPLC-MS/MS with mobile phase consisted of water(0.05%formic acid and 2 mmol·L-1 ammonium acetate)-methanol at the flow rate of 0.55 mL·min-1.The mass detection was performed in positive ionization mode using the electrospray ionization(ESI)source.Dynamic multiple reaction monitoring mode(dMRM)was used to quantify at m/z 798.6→651.5(digoxin)and m/z 801.6→654.5(digoxin-d3),respectively.The selectivity,standard curve,precision and extraction recoveries,matrix effect,and stability were investigated.Results The retention time of both digoxin and internal standard was 1.39 min.The linear range of digoxin in human plasma was among 0.25-8.00 ng·mL-1,a typical standard curve was y=18.08 × 10-2x+29.71 × 10-4(r2=0.995 77).The intra-day and inter-day accuracies of digoxin were less than 15%Extraction recovery rate was 91.00%-99.50%.Stability studies showed good results.Matrix factor normalized by internal standard was within acceptance criteria.The measurement results were in line with the national requirement of External quality evaluation.This method was fully verified and applied to determine the plasma digoxin concentrations of 65 pediatric patients.Conclusion This LC-MS/MS method was simple,rapid and accurate.It is approved appropriate and practical for the therapeutic drug monitoring of digoxin in routine clinical laboratory practice,especially for children.
10.Identification and quality evaluation of germplasm resources of commercial Acanthopanax senticosus based on DNA barcodes and HPLC
Shan-hu LIU ; Zhi-fei ZHANG ; Yu-ying HUANG ; Zi-qi LIU ; Wen-qin CHEN ; La-ha AMU ; Xin WANG ; Yue SHI ; Xiao-qin ZHANG ; Gao-jie HE ; Ke-lu AN ; Xiao-hui WANG ; Sheng-li WEI
Acta Pharmaceutica Sinica 2024;59(7):2171-2178
italic>Acanthopanax senticosus is one of the genuine regional herb in Northeast China. In this study, we identified the germplasm resources of commercial

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