1.Study on the Treatment of Dampness Stagnated in the Triple Energizer Based on the Theory of"Qi Transformation Leading to the Removal of Pathogenic Dampness"
Xiao-Ying MO ; Wei-Jun RUAN ; Feng-Ling ZHENG ; Huan-Huan LUO
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(4):1048-1052
The statement of"qi transformation leading to the removal of pathogenic dampness"was recorded in Wen Bing Tiao Bian(Analysis on Epidemic Febrile Diseases)written by the Qing Dynasty physician WU Ju-Tong.Dampness in the triple energizer is caused by the dysfunction of qi transformation,and the treatment of dampness must be based on the activation of qi movement and focused on the promotion of qi movement and the restoration of the qi transformation in the triple energizer.For the treatment of dampness attack in the upper energizer,therapies of dispersing lung to smooth qi and resolving dampness to relieve the obstruction are recommended.For the treatment of dampness obstruction in the middle energizer,therapy of activating spleen qi by strengthening spleen and moving qi is stressed for helping the removal of dampness and for the eradication of the source of dampness.For the treatment of dampness stagnation in the lower energizer,therapy of draining dampness with sweet-light medicines and activating yang can be used according to the illness status.The three methods of treating dampness,namely dispersing the upper energizer,activating the middle energizer and draining the lower energizer,all embody the mechanism of"qi transformation leading to the removal of pathogenic dampness",and the therapies of dispersing lung with light medicines,inducing perspiration by opening striated layer,eliminating dampness with aromatics and draining dampness with sweet-light medicines should be used in accordance with the syndromes.The elucidation of the academic thoughts of"qi transformation leading to the removal of pathogenic dampness"can provide theoretical reference for the fundamental research of dampness syndrome and clinical application of therapies for resolving dampness in Chinese medicine.
2.The Roles of Deubiquitinases in Renal Cell Carcinoma
Progress in Biochemistry and Biophysics 2024;51(2):276-299
Renal cell carcinoma (RCC) is the primary malignant neoplasm. The ubiquitin-proteasome system (UPS) is crucial to the control of protein level and regulation of physiological and pathological processes. Deubiquitinases (DUBs), key components of UPS, specifically removing ubiquitin chains from the target protein, have showed crucial roles for protein homeostasis and quality control by rigidly regulating the balance between ubiquitination and deubiquitination in normal physiology. Accumulating studies indicate that abnormal function DUBs is associated with the progression and metastasis of RCC. Depending on the substrates, some DUBs may suppress RCC while others promote. Herein, we review recent research advances in RCC-associated DUBs, describe their classification, functional roles, summarize the role and mechanisms of action of DUBs in RCC and discuss the potential of targeting DUBs for cancer treatment.
3.Effect of Simo decoction on the regulation of NLRP3/Caspase-1/GSDMD signal pathway on duodenal microinflammation in rats with functional dyspepsia
Qin LIU ; Xiao-Yuan LIN ; Ling-Feng YANG ; Qian LUO ; Yun-Zong HAN ; Si-Qing CHEN ; Hai-Yue ZHANG ; Shu ZHOU ; Sai-Nan ZHOU
The Chinese Journal of Clinical Pharmacology 2024;40(1):67-71
Objective To investigate the effects of Simo decoction on duodenal microinflammation and NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)signaling pathway in rats with functional dyspepsia(FD).Methods The FD model was established by multifactorial method.SD rats were randomly divided into normal group,model group(FD model),positive control group(gavage administration of 0.305 mg·kg-1 mosapride injection)and experimental-H,-M,-L groups(gavage administration of 5.62,2.81,1.40 g·kg-1 Simo decoction).Small intestinal advancement rate and gastric emptying rate was determined;the levels of interleukin(IL)-1 β and IL-18 in serum were determined by enzyme linked immunosorbent assay(ELISA);the protein expression of NLRP3 and GSDMD in duodenal tissue was detected by Western blotting.Results The gastric emptying rates of normal,model,positive control and experimental-H,-M,-Lgroupswere(58.34±5.72)%,(29.16±8.37)%,(48.77±6.10)%,(48.35±6.04)%,(48.20±3.49)%and(39.24±4.20)%;the small intestinal propulsion rates were(82.01±7.55)%,(41.95±9.53)%,(64.61±10.18)%,(75.04±9.76)%,(60.58±7.13)%and(45.89±7.40)%;serum IL-1 β expression were(12.86±0.88),(43.73±4.60),(18.84±0.86),(24.61±1.57),(19.14±0.77)and(29.04±0.72)pg·mL-1;IL-18 expressions were(95.00±3.74),(170.60±8.78),(108.50±3.05),(118.90±3.45),(99.90±8.70)and(141.00±3.71)pg·mL-1;the relative expression levels of NLRP3 proteins were 0.32±0.02,0.84±0.05,0.42±0.03,0.48±0.02,0.61±0.04 and 0.62±0.05;the relative expression levels of GSDMD proteins were 0.34±0.05,0.93±0.06,0.35±0.03,0.52±0.02,0.53±0.06 and 0.55±0.05,respectively.Compared with the normal group,the above indexes in the model group have statistical significance;compared with the model group,the above indexes in the experimental-H group and the positive control group also have statistical significance(P<0.01 or P<0.05).Conclusion Simo decoction can effectively improve the general condition and duodenal microinflammation in FD rats,and the mechanism may be related to the inhibition of duodenal NLRP3/Caspase-1/GSDMD signaling pathway.
4.Variation rules of main secondary metabolites in Hedysari Radix before and after rubbing strip
Xu-Dong LUO ; Xin-Rong LI ; Cheng-Yi LI ; Peng QI ; Ting-Ting LIANG ; Shu-Bin LIU ; Zheng-Ze QIANG ; Jun-Gang HE ; Xu LI ; Xiao-Cheng WEI ; Xiao-Li FENG ; Ming-Wei WANG
Chinese Traditional Patent Medicine 2024;46(3):747-754
AIM To investigate the variation rules of main secondary metabolites in Hedysari Radix before and after rubbing strip.METHODS UPLC-MS/MS was adopted in the content determination of formononetin,ononin,calycosin,calycosin-7-glucoside,medicarpin,genistein,luteolin,liquiritigenin,isoliquiritigenin,vanillic acid,ferulic acid,γ-aminobutyric acid,adenosine and betaine,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used for chemical pattern recognition to explore differential components.RESULTS After rubbing strip,formononetin,calycosin,liquiritigenin and γ-aminobutynic acid demonstrated increased contents,along with decreased contents of ononin,calycosin-7-glucoside and vanillic acid.The samples with and without rubbing strip were clustered into two types,calycosin-7-glucoside,formononetin,γ-aminobutynic acid,vanillic acid,calycosin-7-glucoside and formononetin were differential components.CONCLUSION This experiment clarifies the differences of chemical constituents in Hedysari Radix before and after rubbing strip,which can provide a reference for the research on rubbing strip mechanism of other medicinal materials.
5.Clinical application of split liver transplantation: a single center report of 203 cases
Qing YANG ; Shuhong YI ; Binsheng FU ; Tong ZHANG ; Kaining ZENG ; Xiao FENG ; Jia YAO ; Hui TANG ; Hua LI ; Jian ZHANG ; Yingcai ZHANG ; Huimin YI ; Haijin LYU ; Jianrong LIU ; Gangjian LUO ; Mian GE ; Weifeng YAO ; Fangfei REN ; Jinfeng ZHUO ; Hui LUO ; Liping ZHU ; Jie REN ; Yan LYU ; Kexin WANG ; Wei LIU ; Guihua CHEN ; Yang YANG
Chinese Journal of Surgery 2024;62(4):324-330
Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.
6.Effects of template and pore-forming agent method on the structure and drug delivery of porous maltodextrin
Zhe LI ; Xiao-sui LUO ; Wei-feng ZHU ; Qiong LI ; Yong-mei GUAN ; Zheng-ji JIN ; Li-hua CHEN ; Liang-shan MING
Acta Pharmaceutica Sinica 2024;59(8):2381-2395
This study using maltodextrin as raw material, 1%-5% polyvinylpyrrolidone K30 as template agent, 1%-5% ammonium bicarbonate as pore-forming agent, curcumin and ibuprofen as model drugs. Porous maltodextrin was prepared by template and pore-forming agent methods, respectively. The structure and drug delivery behavior of porous maltodextrin prepared by different technologies were comprehensively characterized. The results showed that the porous maltodextrin prepared by pore-forming agent method had larger specific surface area (6.449 4 m2·g-1) and pore size (32.804 2 nm), which was significantly better than that by template agent method (3.670 2 m2·g-1, 15.278 5 nm). The adsorption kinetics between porous maltodextrin prepared by pore-forming agent method and curcumin were suitable for quasi-first order adsorption kinetic model, and that between porous maltodextrin and ibuprofen were suitable for quasi-second order adsorption kinetic model. While the adsorption kinetics between porous maltodextrin prepared by template agent method and two model drugs were both suitable for the quasi-first order adsorption kinetic model. In addition, the dissolution behavior analysis showed that the porous maltodextrin prepared by the two technologies can significantly improve the dissolution behavior of insoluble drugs, and the drug release was both carried out by diffusion mechanism, which suitable for the Peppas kinetic release model, but the porous maltodextrin prepared by template agent method had a faster release rate. The change of nozzle diameter had no significant effect on the adsorption process and drug release behavior of porous maltodextrin. In conclusion, the porous maltodextrins prepared by two different technologies were both beneficial to the delivery of insoluble drugs, and the template agent method was the best for delivery of insoluble drugs. This study can provide theoretical basis for the preparation of porous particles, promote the application of porous particles in insoluble drugs, and improve the bioavailability of insoluble drugs.
7.Chemical derivatization strategies for enhancing the HPLC analytical performance of natural active triterpenoids
Huang XIAO-FENG ; Xue YING ; Yong LI ; Wang TIAN-TIAN ; Luo PEI ; Qing LIN-SEN
Journal of Pharmaceutical Analysis 2024;14(3):295-307
Triterpenoids widely exist in nature,displaying a variety of pharmacological activities.Determining triterpenoids in different matrices,especially in biological samples holds great significance.High-performance liquid chromatography(HPLC)has become the predominant method for triterpenoids analysis due to its exceptional analytical performance.However,due to the structural similarities among botanical samples,achieving effective separation of each triterpenoid proves challenging,necessitating significant improvements in analytical methods.Additionally,triterpenoids are characterized by a lack of ultraviolet(UV)absorption groups and chromophores,along with low ionization efficiency in mass spectrometry.Consequently,routine HPLC analysis suffers from poor sensitivity.Chemical derivatization emerges as an indispensable technique in HPLC analysis to enhance its performance.Considering the structural characteristics of triterpenoids,various derivatization reagents such as acid chlorides,rho-damines,isocyanates,sulfonic esters,and amines have been employed for the derivatization analysis of triterpenoids.This review comprehensively summarized the research progress made in derivatization strategies for HPLC detection of triterpenoids.Moreover,the limitations and challenges encountered in previous studies are discussed,and future research directions are proposed to develop more effective derivatization methods.
8.Exploration of the Mechanism of Erzhi Wan in the Treatment of Multiple Myeloma Based on Network Pharmacology,Molecular Docking and Cell Experimental Verification
Meng-Dan SHAN ; Ying-Bin ZHONG ; Man LUO ; Ming-Feng XIAO
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(8):2153-2161
Objective To explore the potential mechanism of Erzhi Wan in the treatment of multiple myeloma(MM)based on network pharmacology,molecular docking and cell experimental verification.Methods Network pharmacology and molecular docking were used to screen the key indicators of drugs-diseases-targets-pathways.MM line RPMI-8226 cells were cultured and given Erzhi Wan intervention.Apoptosis was detected by Annexin V-fluorescein isothiocyanate(FITC)staining.Transwell assay was used to determine cell invasion ability.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the mRNA expressions of protein kinase B(Akt),cyclin D1(CCND1),glycogen synthase kinase 3β(GSK-3β)and c-Myc.Western Blot was used to detect the protein expressions of Akt,phosphorylated protein kinase B(p-Akt),CCND1,c-Myc,GSK-3β and phosphorylated glycogen synthase kinase 3β(p-GSK-3β).Results Fourteen effective components of Erzhi Wan were obtained.There were 142 targets involved in the treatment of MM by Erzhi Wan.The results of pathway enrichment analysis showed that the key targets may be mainly concentrated in cancer pathways,lipids and atherosclerosis.Molecular docking results showed that luteolin and quercetin had good binding activity and stability with GSK-3β.Further cell experimental verification showed that compared with the blank group,the apoptosis rate of cells in the low-,medium-and high-dose groups of Erzhi Wan was significantly increased,the number of cell invasion was decreased,the mRNA and protein levels of GSK-3β were significantly increased,and the mRNA and protein levels of CCND1,Akt and c-Myc were significantly decreased in a dose-dependent manner,among them,the differences in the medium-and high-dose groups being statistically significant(P<0.05 or P<0.01).Conclusion The therapeutic effect of Erzhi Wan on MM may be achieved by promoting the expression of GSK-3β and inhibiting the Akt/GSK-3β/CCND1/c-Myc signaling pathway through key active components such as luteolin and quercetin.
9.Fluid shear promotes apoptosis of glomerular endothelial cells by activation of Piezo 1
Menglin LUO ; Feng ZHENG ; Xinyao JI ; Caihong QI ; Yuheng XIAO ; Changchun NIU
Basic & Clinical Medicine 2024;44(9):1236-1242
Objective To investigate the effect of fluid shear(FS)on apoptosis of glomerular epithelial cells(GECs)and the role of Piezo 1 protein in it.Methods GECs(glomerular epithelial cells)of SD rat were cul-tured.Fluid shear stimulation was simulated by a Flexcell-T5000 tensiometer.Apoptosis level was detected by flow cytometry.The expression of Piezo 1 proteins in GECs was detected by immunofluorescence staining.The activating of Piezo 1 channels by fluid shear was observed using Ca2+indicator(Cal-590 AM).The effect of Piezo 1 on apop-tosis in GECs was analyzed after modulating the function or expression of Piezo 1 protein using the chemical activa-tor Yoda1,the inhibitor GsMtx 4 was regulated by lentivirus Lv-shPiezo 1.Results Compared with the blank controlgroup,apoptosis increased in the fluid shear group(P<0.05).The rate of apoptosis increased with the enhancing of fluid shear strength;Piezo 1 was commonly expressed in GECs.Fluid shear activated Piezo 1 chan-nel and enhanced expression of Piezo 1.The agonist Yoda1 promoted the apoptosis of GECs GsMtx 4 inhibited the apoptosis induced by fluid shear.Lv-shPiezo 1 knocked down the expression of Piezo 1 in GECs and the apoptosis rate of GECs in the knockdown group was reduced as compared to that in the control group and Lv-Ctrl group(P<0.05).Conclusions Fluid shear may promote apoptosis of GECs by activation of Piezo 1 and by enhancing expression of Piezo 1.
10.Changes in the microstructure and bone mineral density of vertebral tra-becular bone in the early stages of spinal Mycobacterium tuberculosis in-fection
Jun-Bao CHEN ; Yi LUO ; Nan-Jun XIONG ; Xiao-Jiang HU ; Chao-Feng GUO ; Qi-Le GAO ; Yan-Bing LI
Chinese Journal of Infection Control 2024;23(8):1001-1006
Objective To observe and compare the changes of vertebral bone mineral density(BMD)in the early stages of spinal Mycobacterium tuberculosis infection.Methods Patients who underwent spinal surgery at Xiangya Hospital,Central South University from January 1 to December 31,2023 were continuously enrolled(spinal tuber-culosis group),based on gender matching,non-spinal tuberculosis surgical patients treated for spinal stenosis were selected as the control group.Dual-energy X-ray scans were performed on the enrolled patients,difference in verte-bral BMD between two groups of patients was compared.An animal model of spinal Mycobacterium tuberculosis in-fection(referred to as the animal model)was constructed,differences in microstructure of trabecular bone between spinal tuberculosis group and control group was compared,and the bone volume/tissue volume(BV/TV),the thickness of trabecular bone(Tb.Th),the number of trabecular bone(Tb.N),and sparse density of trabecular(Tb.Sp)were used as evaluation indexes to further analyze the bone quality differences between the diseased verte-brae and the neighboring vertebrae.Results 69 patients were included in the spinal tuberculosis group and the con-trol group,respectively.The BMD of patients in the spinal tuberculosis group(0.793[0.712,0.869]g/cm2)was lower than that of the control group(0.907[0.800,1.020]g/cm2),difference was statistically significant(P<0.05).Microstructure of trabecular bone BV/TV([18.4±5.4]%),Tb.Th([0.124±0.010]mm)in the spinal tuberculosis group of animal model were significantly altered compared with BV/TV([22.6±3.2]%),Tb.Th([0.160±0.017]mm)in the control group(both P<0.05).In the spinal tuberculosis group,microstructure of diseased vetebral trabecular bone BV/TV([25.5±6.7]%)and Tb.N([1.871±0.443]/mm)were significantly lower than BV/TV([26.6±6.8]%)and Tb.N([1.969±0.454]/mm)in the neighboring vertebrae,both with statistically difference(both P<0.05).Conclusion In the early stages of spinal Mycobacterium tuberculosis infec-tion,microstructure of vertebral trabecular bone can be altered,leading to a decrease in BMD.

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