1.Research progress on polysaccharides in the cell wall of Mycobacterium tuberculosis
Ming CAI ; Jing ZHOU ; Sijie YANG ; Shidong ZHAO ; Yan YIN ; Fan CHEN
Journal of Public Health and Preventive Medicine 2025;36(5):134-139
Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis, which is primarily transmitted through the respiratory tract, and remains one of the diseases with the highest mortality rate of single-pathogen infections globally. The cell wall polysaccharides of M. tuberculosis are critical for maintaining bacterial structure, mediating pathogenesis, and enabling immune evasion. Lipoarabinomannan (LAM), a key polysaccharide component, has revolutionized non-invasive diagnostic technologies as a TB biomarker, while polysaccharide-based vaccines have emerged as innovative strategies for TB prevention. This review systematically examines the composition, subcellular distribution, and functional roles of M. tuberculosis cell wall polysaccharides in bacterial metabolism, drug resistance, and immune regulation. A particular emphasis is placed on recent advancements in LAM-based diagnostics and vaccine development. Future studies should utilize advanced technologies to precisely characterize the structural features of TB polysaccharides and explore their biological functions, providing a foundation for targeted diagnostic and therapeutic innovations. This article aims to provide reference for advancing both basic research and clinical applications related to M. tuberculosis.
2.Study on bioequivalence evaluation of Pemirolast potassium tablets in Chinese healthy volunteers on an empty stomach/after meals
Yi-Ming MA ; Wang HU ; Feng ZHANG ; Wen ZHANG ; Sheng-Long ZHAO ; Yang CAO ; Jing XIE ; Huan ZHOU ; Shun-Wang HUANG
Chinese Pharmacological Bulletin 2024;40(6):1075-1081
Aim To compare the pharmacokinetics of pemirolast potassium tablets in healthy subjects in Chi-na under single fasting and postprandial conditions,and to evaluate the bioequivalence of the test prepara-tion(T)and the reference preparation(R).Methods A randomized,open-ended,single-dose,two-cycle,double-cross bioequivalence trial design was adopted,and 26 and 30 subjects were enrolled in the fasting group and the postprandial group,respectively,and 10 mg of the test preparation and the reference preparation were taken in the fasting or postprandial state each cy-cle,and venous blood was collected at the designed time points before and after the administration cycle.The concentration of pemirolast potassium in plasma was determined by LC-MS/MS method,and the phar-macokinetic parameters were calculated with PhoenixTM WinNonlin ?(8.3)software,and the bioequivalence analysis of the two preparations was performed.Re-sults The t1/2 of the test preparation and the reference preparation was(4.44±0.91)h and(4.49±0.93)h,respectively;the median tmax was(1.96±1.29)h and(2.18±1.25)h,respectively;the Cmax was(867.12±205.56)μg·L-1 and(863.35±172.03)μg·L-1,respectively;the AUC0-t was(5 513.23±1463.67)h·μg·L-1 and(5 661.32±1 628.65)h·μg·L-1,respectively;AUC0_∞ was(5 699.81±1477.68)h·μg·L-1 and(5 849.44±1 644.75)h·μg·L-1,respectively.The statistical results of the 90%confidence intervals of the main pharmacokinetic parameters Cmax,AUC0-t,and AUC0-∞ was 92.49%~107.53%,94.71%~100.67%and 95.28%~100.27%,respectively,all of which were within the range of 80.00%~125.00%,and the safety of the tested preparation and the reference preparation was good when taken orally on an empty stomach.The t1/2 of single oral administration after prandial administra-tion of the tested preparation and the reference prepara-tion was(4.46±0.78)and(4.51±0.84)h,respec-tively;the median tmax was(3.08±1.36)h and(3.28±1.28)h,respectively;the Cmax was(683.83±111.87)μg·L-1 and(689.77±110.24)μg·L-1,respectively;the AUC0-t was(5 695.99±1566.05)h·μg·L-1 and(5 773.60±1 551.04)h·μg·L-1,respectively;the AUC0-∞ was(5 914.06±1 551.86)h·μg·L-1 and(5 967.30±1552.89)h·μg·L-1,respectively.The 90%confi-dence interval of Cmax,AUC0-t,and AUC0-∞ was 93.56%~104.69%,96.43%~100.83%,and 97.29%~101.14%,respectively,which was in the range of 80.00%~125.00%,and the safety of the tested preparation and the reference preparation was good after meals.Conclusion In the state of fasting and postprandial single oral administration,the two kinds of pemirolast potassium tablets have good bio-equivalence.
3.Mechanism of effect of rosiglitazone on pancreatic cancer in diabetic mice based on impact of PPARy on glucose transport and metabolism
Rui-Ping HU ; Li-Feng SHANG ; He-Jing WANG ; Hong-Xia CHE ; Ming-Liang WANG ; Huan YANG ; Yuan-Yuan JIN ; Fei-Fei ZHANG ; Jian-Ling ZHANG
Chinese Pharmacological Bulletin 2024;40(7):1325-1334
Aim To explore the mechanism of the effect of rosiglitazone(Rsg)on the pancreatic cancer in diabetic mice based on the impact of PPARγ on glu-cose transport and metabolism.Methods A high-fat and high sugar diet combined with STZ was used to construct T2DM model;T2DM mice and normal mice were subcutaneously injected with PANC02 cells to construct a transplanted tumor model.T2DM trans-planted tumor mice and normal transplanted tumor mice were divided into the following groups:Rsg,PPARy inhibitor(PIN-2),rosiglitazone+PPARγ in-hibitor(Rsg+PIN-2),and normal transplanted tumor mice(NDM)and T2DM transplanted tumor mice(DM)were used as control groups,respectively.Tis-sue samples were collected after intervention.Tissue pathological changes were observed by HE staining.The expressions of Ki67 and PCNA proteins were de-tected by immunohistochemistry.Cell apoptosis was detected by TUNEL assay.The expression of PPARγwas detected by immunofluorescence.The expressions of Glucokinase,GLUT2,Nkx6.1,PDX-1RT-PCR were determined by Western blot.Results Rsg could significantly reduce the tumor mass,pathological chan-ges,Ki67 and PCNA expression of transplanted tumors(P<0.05),increase cell apoptosis and the expression of PPARγ,Glucokinase,GLUT2,Nkx6.1,PDX-1 proteins in NDM and DM mice(P<0.05).PIN-2 could reverse the indicator changes caused by Rsg in NDM and DM mice.However,compared with NDM mice,the above related indicators of the DM group mice were more sensitive to Rsg and PIN-2.Conclu-sions Compared to non-diabetic pancreatic cancer,rosiglitazone can more sensitively inhibit the prolifera-tion of pancreatic cancer with T2DM,induce apopto-sis,and reprogram the metabolism of pancreatic cancer with T2DM by activating PPA Rγ and altering the ex-pression of glucose and lipid metabolism genes,there-by exerting an anti-cancer effect.
4.Mechanisms of dendrobium polysaccharides in alleviating acetaminophen-induced hepatic injury through anti-inflammatory and antioxidant reaction
Yue JING ; You-Gen WANG ; Zhi-Hui YANG ; Ming ZENG
Chinese Pharmacological Bulletin 2024;40(8):1539-1545
Aim To investigate the protective effects of dendrobium polysaccharide(DOP)against paraceta-mol(APAP)-induced liver injury in mice and eluci-date its underlying mechanism.Methods Healthy male Kunming mice were randomly assigned to the fol-lowing groups:control group,APAP model group,low,medium,high-dose DOP intervention group(225,450,900 mg·kg-1),and DOP control group.The APAP model group was given 300 mg·kg-1 per day,the DOP intervention group was given DOP for 2 h and then APAP was given,and the remaining groups received an equal volume of normal saline daily for sev-en consecutive days.After the final administration,se-rum and liver samples from the mice were collected and tested after 20 hours.Liver morphology and liver coef-ficient were examined.Liver histopathological altera-tions and apoptosis were examined using HE staining and TUNEL staining.Additionally,medium biochemi-cal indexes were assessed in serum and liver tissue u-sing kits.The levels of oxidative stress,inflammation,and apoptosis-related proteins in liver tissue were de-termined using Western blotting.Results In the APAP model group,liver coefficient increased signifi-cantly,the number of liver vacuolar necrosis and apop-tosis cells increased,and the serum ALT and AST lev-els significantly increased.Compared with the APAP group,the liver coefficient,serum ALT and AST levels were significantly reduced,and the liver pathology was improved after DOP intervention,especially in the 900 mg·kg-1 group.The levels of oxidative stress and in-flammation in the APAP group increased,and the ex-pression of apoptosis,inflammation and oxidative stress related proteins in liver was unbalanced.DOP inter-vention,especially in the 900 mg·kg-1 group,could significantly reverse the oxidative stress,apoptosis and inflammatory response induced by APAP in liver,and increase the expression levels of Nrf2 and HO-1,but reduce the expression levels of NLRP3 and HMGB1.Conclusions The hepatoprotective mechanism of DOP is mainly due to its antioxidant and anti-inflammatory response,which may be related to the activation of Nrf2/HO-1 pathway and the inhibition of HMGB1/NL-RP3 pathway by DOP.
5.Dynamic characterization of neuronal injury in cortex and hippocampus of mice after acute cerebral ischemia/reperfusion
Tong LI ; Jia-Ming BAI ; Yi-Jun SHI ; Cai-Ming WEN ; Lin CUI ; Jing-Xian YANG ; Hong-He XIAO
Chinese Pharmacological Bulletin 2024;40(9):1708-1718
Aim To dynamically characterize neuronal damage in the cortex and hippocampus of mice follow-ing acute cerebral ischemia/reperfusion(I/R).Meth-ods Male C57BL/6J mice weighing 25-28 g under-went middle cerebral artery occlusion using the fila-ment method,followed by 1 hour of reperfusion to es-tablish the acute cerebral I/R injury mouse model.The experiment comprised a sham surgery group,I/R-6 h group,I/R-24 h group,and I/R-72 h group.Longa neurological function score was used to assess the neu-rological function.Triphenyltetrazolium chloride(TTC)staining was conducted to detect cerebral in-farct volume.Hematoxylin and eosin(HE)staining was utilized to observe brain tissue pathological dam-age.Nissl staining was performed to evaluate neuronal damage.Immunofluorescence histochemistry staining was employed to assess the activation of astrocytes and microglia,as well as neuronal loss.Transmission elec-tron microscopy was used to examine mitochondrial damage in hippocampal neurons.Western blot analysis was conducted to detect the expression levels of mito-chondrial fission-fusion-related proteins p-Drp1/Drp1,Mff,Fis1,and OPA1.Results With prolonged cere-bral I/R time,neurological functional impairment,cerebral infarct volume,neuronal damage in the cortex and hippocampus,glial cell activation,neuronal loss,and mitochondrial damage gradually worsened in mice.The expression of mitochondrial fission-related proteins increased gradually,while the expression of mitochon-drial fusion-related proteins decreased gradually.Con-clusions Neuronal pathological damage,such as glial cell activation,neuronal loss,and mitochondrial dam-age,is gradually aggravated with prolonged cerebral I/R time,which may be associated with mitochondrial dynamics imbalance.
6.Synthesis and in vitro anti-small cell lung cancer effects of MnFe2O4@HMD nanozyme
Jing-Chuan HE ; Ting-Ting LI ; Xiao-Qin PAN ; Ming GAO ; Jie YANG
Chinese Pharmacological Bulletin 2024;40(11):2075-2082
Aim To synthesize MnFe2O4@HMD nanozyme and investigate its anti-small cell lung cancer activity.Methods HMD was synthesized by esterifi-cation and acylation reactions,MnFe2O4 was synthe-sized by co-precipitation,and MnFe2O4@HMD was synthesized under ultrasound and magnetic stirring.MnFe2O4@HMD was characterized by FTIR,UV-vis,Zeta potential,and XRD.The morphology and particle size distribution of MnFe2O4@HMD were assessed by TEM and DLS.MTT assay and live/dead cell staining were used to evaluate the effect of MnFe2O4@HMD on the viability of H1 688 cells.Confocal microscopy was used to observe the uptake of MnFe2O4@HMD by H1688 cells.DCF-HA staining and GSH kit were used to detect the effect of MnFe2O4@HMD on the levels of ROS and GSH in H1688 cells.Western blot was used to detect the effect of MnFe2O4@HMD on the expres-sion of apoptosis-related proteins Bax and Bcl-2 in H1688 cells.Results MnFe2O4@HMD nanozymes were successfully synthesized,with zeta potential and particle size of-14.57±1.81 mV and 27.1 nm,re-spectively.MnFe2O4@HMD had a concentration-de-pendent toxicity effect on H1688 cells.H1688 cells showed a good uptake behavior of MnFe2O4@HMD.MnFe2O4@HMD could induce ROS production and GSH consumption in H1688 cells in a concentration-dependent manner,and up-regulated the expression of pro-apoptotic protein Bax and down-regulated anti-ap-optotic protein Bcl-2 in H1688 cells.Conclusion MnFe2O4@HMD shows good killing effect on H1688 cells,which could lead to the elevation of ROS and the depletion of GSH,and induce apoptosis in H1688 cells.
7.Effects of astragalus angelica on apoptosis and expression of Bax and caspase-3/9 in rabbit chondrocytes after fresh osteochondral allograft
Wan-Tao DONG ; Pan YANG ; Xiu-Juan YANG ; Shi-Ming QIU ; Peng YUAN ; Jing-Yi LIU ; Jiu-Mei HUANG ; Yu ZHOU
Chinese Pharmacological Bulletin 2024;40(12):2288-2294
Aim To observe the effect of Astragalus membranaceus and Angelica sinensis on the apoptosis of chondrocytes,and to investigate the effect of Astrag-alus membranaceus and Angelica sinensis on the sur-vival of fresh ostecartilage allograft.Methods Forty-eight 4-month-old New Zealand white rabbits,half male and half female,were randomly divided into sham operation group,model group,positive group and As-tragalus and Angelica 5∶1 group.In addition to the sham operation group,the other groups were both male and female donors and recipients for knee joint osteo-cartilage cross transplantation modeling.After 8 weeks of drug intervention,samples were taken for general observation,HE staining,saffrane-O staining,immu-nohistochemical staining,qPCR and Western blot de-tection.Results Compared with model group,As-tragalus and Angelica 5∶1 group and positive group,the repair site healed better,the morphology of osteo-chondrocytes tended to be normal,and the division and proliferation were obvious.Proteoglycan deposition in-creased and type Ⅱ collagen content was higher,the differences were statistically significant(P<0.05).qPCR and Western blot results showed that compared with model group,the mRNA and protein expressions of Bax,caspase-3 and caspase-9 in other groups were significantly decreased(P<0.05).Conclusion As-tragalus and Angelica can promote the survival of fresh osteochondral allograft,and its mechanism may be re-lated to promoting collagen production,promoting chondrocyte proliferation and inhibiting chondrocyte apoptosis.
8.Ultra-fast track anesthesia management for transcatheter mitral valve edge-to-edge repair
Zhi-Yao ZOU ; Da ZHU ; Yi-Ming CHEN ; Shou-Zheng WANG ; Jian-Bin GAO ; Jing DONG ; Xiang-Bin PAN ; Ke YANG
Chinese Journal of Interventional Cardiology 2024;32(5):250-256
Objective To retrospectively analyze the ultra-fast track anesthesia(UFTA)methods and perioperative anesthesia management experiences of transcatheter mitral valve edge-to-edge repair(TEER)in the treatment of functional mitral regurgitant.Methods In this retrospective study,patients underwent the TEER procedure and received UFTA in Fuwai Yunnan Hospital,from May 2022 to September 2022 for heart failure combined with moderate to severe or severe functional mitral regurgitant were included.Baseline,preoperative complications,cardial function and anesthesia classification,amino-terminal probrain natriuretic peptide(NT-proBNP),ultrasound examination results,surgery time,extubation time,intraoperative anesthetic and vasoactive drug,complications related to TEER and UFTA,perioperative,and postoperative 30-day and one-year follow-up data were collected.All perioperative clinical data were recorded and analyzed.Results A total of 30 patients were enrolled,11 patients(36.7%)were female,mean age was(63.6±6.1)years,NYHA classification IV 14 patients(46.7%),left ventricular ejection fraction(LVEF)(36.0±8.1)%,the end-diastolic volume of the left ventricle(66.0±8.2)mm,mitral regurgitation 4+14 patients(56.7%),3+17 patients(43.3%),NT-proBNP(1 934.1±1 973.5)pg/ml,1 patient(3.3%)used high-dose vasoactive drugs during surgery.All patients did not experience nausea,vomiting,delirium,respiratory depression,perioperative transesophageal echocardiography-related gastrointestinal bleeding,pericardial effusion,cerebrovascular accidents,emergency surgery or secondary intervention,or other serious adverse events within 24 hours after surgery.No 30-day all-cause death occurred;the mean postoperative hospital stay was(7.4±2.8)days.All patients completed one-year follow-up,LVEF(37.6±11.1)%,the end-diastolic volume of the left ventricle(63.2±8.6)mm,mitral regurgitation 2+7 patients(23.3%),1+23 patients(76.7%),NT-proBNP(1 949.2±2 576.6)pg/ml.Conclusions Ultra-fast track anesthesia can be safely applied to TEER in treating functional mitral regurgitant patients.
9.Network pharmacological study and experimental validation of Rhizoma Chuanxiong volatile oil in the treatment of angina pectoris
Ming YANG ; Chaoping WANG ; Zhiqiang LEI ; Bo LIU ; Hua ZHANG ; Jing LUO
Acta Laboratorium Animalis Scientia Sinica 2024;32(7):867-878
Objective Network pharmacology and animal experiments were performed to study and verify the therapeutic effect of Rhizoma Chuanxiong volatile oil on angina pectoris.Methods Volatile oil components were screened using steam distillation,gas chromatography-mass spectrometry,and oral bioavailability.Targets of these components were identified using Pubchem,SwissTarget,DisGeNET,and DrugBank databases as well as R language.Angina pectoris-related targets and intersection targets were obtained.Protein-protein interactions were analyzed using the STRING database.The ClusterProfiler package in R was used to analyze the gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment of the intersecting targets,and Cytoscape was used to construct herbal-component-target-pathway networks.Molecular docking analysis was conducted using AutoDock Vina 1.2.3,Pymol 3.0,and Discovery Studio 2016 software to evaluate the affinity between key targets and the main volatile oil components.Finally,the therapeutic effect of Rhizoma Chuanxiong volatile oil on angina pectoris was verified by animal experiments.Results In total,10 volatile oil components and 22 key targets were identified.They were closely related to neurotransmitters,receptors on synaptic membranes,material metabolism,neuroactive ligand-receptor interaction,retinol metabolism,and drug metabolism-cytochrome P450 pathways.The molecular docking result showed that 3-butylidenephthalide,alpha-selinene,trans-ligustilide,and other volatile oil components combined with several key targets play therapeutic roles.Animal experiments showed that the volatile oil of Rhizoma Chuanxiong can regulate the ejection fraction,fractional shortening,stroke volume,and left ventricular internal diameter in systole and the activities of lactate dehydrogenase,creatine kinase and aspartate aminotransferase;promote the expression of ADRA1A and CHRM5 proteins in damaged cardiomyocytes;improve the state of myocardial fibers;reduce intercellular space;and reduce inflammatory cell infiltration.Conclusions The volatile oil of Ligusticum wallichii can effectively protect damaged myocardial tissue and thus has a role in treating angina pectoris.
10.Comparison of Clinical Characteristics of JAK2,CALR and Tri-Negative Driving Mutant Type in Patients with Essential Thrombocythemia
Yu-Meng LI ; Er-Peng YANG ; Zi-Qing WANG ; De-Hao WANG ; Ji-Cong NIU ; Yu-Jin LI ; Jing MING ; Ming-Qian SUN ; Zhuo CHEN ; Wei-Yi LIU ; Yan LYU ; Xiao-Mei HU
Journal of Experimental Hematology 2024;32(1):197-201
Objective:To investigate the relationship between mutated genes and clinical features in patients with essential thrombocythemia(ET).Methods:The clinical data of 69 patients with ET from October 2018 to March 2022 were retrospectively analyzed.According to driver mutation type,patients were divided into JAK2 group,CALR group and triple-negative group.The sex,age,cardiovascular risk factors,thrombosis,splenomegaly,routine blood test and coagulation status of patients in three groups were analyzed.Results:Among 69 ET patients,46 cases were associated with JAK2 mutation,14 cases with CALR mutation,8 cases with triple-negative mutation,and one with MPL gene mutation.There were no significant differences in age and sex among the three groups(P>0.05).The highest thrombotic rate was 26.09%(12/46)in JAK2 group,then 12.5%(1/8)in triple-negative group,while no thrombotic events occurred in CALR group.The incidence of splenomegaly was the highest in JAK2 group(34.78%),while no splenomegaly occurred in triple-negative group.The white blood cell(WBC)count in JAK2 group was(9.00±4.86)× 109/L,which was significantly higher than(6.03±2.32)× 109/L in CALR group(P<0.05).The hemoglobin(Hb)and hematocrit(HCT)in JAK2 group were(148.42±18.79)g/L and(0.44±0.06)%,respectively,which were both significantly higher than(131.00±15.17)g/L and(0.39±0.05)%in triple-negative group(P<0.05).The platelet(PLT)in JAK2 group was(584.17±175.77)× 109/L,which was significantly lower than(703.07±225.60)× 109/L in CALR group(P<0.05).The fibrinogen(Fg)in JAK2 and triple-negative group were(2.64±0.69)g/L and(3.05±0.77)g/L,respectively,which were both significantly higher than(2.24±0.47)g/L in CALR group(P<0.05,P<0.01).The activated partial thromboplastin time(APTT)in triple-negative group was(28.61±1.99)s,which was significantly decreased compared with(31.45±3.35)s in CALR group(P<0.05).Conclusions:There are differences in blood cell count and coagulation status among ET patients with different driver gene mutations.Among ET patients,JAK2 mutation is most common.Compared with CALR group,the thrombotic rate,WBC and Fg significantly increase in JAK2 group,while PLT decrease.Compared with triple-negative group,the incidence of splenomegaly and HCT significantly increase.Compared with CALR group,Fg significantly increases but APTT decreases in triple-negative group.


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