1.Effects of Shujin Jiannao Formula (舒筋健脑方) on Neural Repair and PI3K-Akt-mTOR Pathway of Brain Tissue in Cerebral Palsy Model Rats
Ruiqin YU ; Yanjun MO ; Houjun ZHANG ; Gang LIU ; Zhuoluo ZHOU ; Zechen RUAN ; Lin XU ; Xiaohong MU
Journal of Traditional Chinese Medicine 2025;66(10):1038-1045
ObjectiveTo explore the possible mechanisms of Shujin Jiannao Formula (舒筋健脑方) for cerebral palsy. MethodsThirty 7-day-old SD rats were randomly divided into normal group, model group, and Shujin Jiannao Formula group, with 10 rats in each group. The model group and Shujin Jiannao Formula group established a cerebral palsy model by the classic Rice-Vannucci method. After successful modeling, rats in Shujin Jiannao Formula group were given Shujin Jiannao Formula 16 g/(kg·d) by gavage, while the normal group and model group were given normal saline 10 ml/(kg·d) by gavage once a day. After one week of intervention, the rats' body weight was measured, and Zea-Longa scores, the righting reflex test, and the hindlimb suspension test were conducted for assessment; hematoxylin-eosin (HE) staining and Nissl staining were used to observe pathological changes in brain tissue, and the number of Nissl-positive neurons was counted; enzyme-linked immunosorbent assay (ELISA) was employed to measure levels of inflammatory cytokines in the brain tissue, specifically interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α); immunofluorescence was used to detect the expression levels of neurofilament protein 200 (NF200) and myelin basic protein (MBP) in brain tissue; Western Blot analysis was conducted to determine the protein levels of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt/PKB/Rac), and mammalian target of rapamycin (mTOR) in brain tissue. ResultsCompared with the normal group, rats in the model group showed significantly higher Zea-Longa scores and lower scores in the hindlimb suspension test (P<0.01); pathological findings revealed loose structure in the cerebral cortex, hippocampal atrophy, and neuronal damage in brain tissue. Levels of IL-1β and TNF-α elevated, and the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region reduced, and immunofluorescence intensity of NF200 and MBP, as well as protein expression levels of PI3K and mTOR, significantly decreased (P<0.05 or P<0.01). Compared with the model group, rats in Shujin Jiannao Formula group showed decreased Zea-Longa scores and increased hindlimb suspension test scores (P<0.05); pathological damage in brain tissue alleviated, levels of IL-1β and TNF-α reduced, the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region increased, and the immunofluorescence intensity of NF200 and MBP, as well as the protein levels of PI3K and mTOR, significantly elevated (P<0.05 or P<0.01). There were no statistically significant differences among the groups in body weight, body-turning time, or AKT protein levels in brain tissue (P>0.05). ConclusionShujin Jiannao Formula can improve the neurological function of rats with cerebral palsy, exert neurorestorative effects, and its mechanism of action may be related to the reduction of inflammatory response in brain tissue and the activation of the PI3K/AKT/mTOR signaling pathway.
2.Medication rules and mechanisms of treating chronic renal failure by Jinling medical school based on data mining, network pharmacology, and experimental validation.
Jin-Long WANG ; Wei WU ; Yi-Gang WAN ; Qi-Jun FANG ; Yu WANG ; Ya-Jing LI ; Fee-Lan CHONG ; Sen-Lin MU ; Chu-Bo HUANG ; Huang HUANG
China Journal of Chinese Materia Medica 2025;50(6):1637-1649
This study aims to explore the medication rules and mechanisms of treating chronic renal failure(CRF) by Jinling medical school based on data mining, network pharmacology, and experimental validation systematically and deeply. Firstly, the study selected the papers published by the inherited clinicians in Jinling medical school in Chinese journals using the subject headings named "traditional Chinese medicine(TCM) + chronic renal failure", "TCM + chronic renal inefficiency", or "TCM + consumptive disease" in China National Knowledge Infrastructure, Wanfang, and VIP Chinese Science and Technology Periodical Database and screened TCM formulas for treating CRF according to inclusion and exclusion criteria. The study analyzed the frequency of use of single TCM and the four properties, five tastes, channel tropism, and efficacy of TCM used with high frequency and performed association rule and clustering analysis, respectively. As a result, a total of 215 TCM formulas and 235 different single TCM were screened, respectively. The TCM used with high frequency included Astragali Radix, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Poria, and Atractylodis Macrocephalae Rhizoma(top 5). The single TCM characterized by "cold properties, sweet flavor, and restoring spleen channel" and the TCM with the efficacy of tonifying deficiency had the highest frequency of use, respectively. Then, the TCM with the rules of "blood-activating and stasis-removing" and "diuretic and dampness-penetrating" appeared. In addition, the core combination of TCM [(Hexin Formula, HXF)] included "Astragali Radix, Rhei Radix et Rhizoma, Poria, Salviae Miltiorrhizae Radix, and Angelicae Sinensis Radix". The network pharmacology analysis showed that HXF had 91 active compounds and 250 corresponding protein targets including prostaglandin-endoperoxide synthase 2(PTGS2), PTGS1, sodium voltage-gated channel alpha subunit 5(SCN5A), cholinergic receptor muscarinic 1(CHRM1), and heat shock protein 90 alpha family class A member 1(HSP90AA1)(top 5). Gene Ontology(GO) function analysis revealed that the core targets of HXF predominantly affected biological processes, cellular components, and molecular functions such as positive regulation of transcription by ribonucleic acid polymerase Ⅱ and DNA template transcription, formation of cytosol, nucleus, and plasma membrane, and identical protein binding and enzyme binding. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis revealed that CRF-related genes were involved in a variety of signaling pathways and cellular metabolic pathways, primarily involving "phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) pathway" and "advanced glycation end products-receptor for advanced glycation end products". Molecular docking results showed that the active components in HXF such as isomucronulatol 7-O-glucoside, betulinic acid, sitosterol, and przewaquinone B might be crucial in the treatment of CRF. Finally, a modified rat model with renal failure induced by adenine was used, and the in vivo experimental confirmation was performed based on the above-mentioned predictions. The results verify that HXF can regulate mitochondrial autophagy in the kidneys and the PI3K-Akt-mammalian target of rapamycin(mTOR) signaling pathway activation at upstream, so as to alleviate renal tubulointerstitial fibrosis and then delay the progression of CRF.
Data Mining
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Drugs, Chinese Herbal/chemistry*
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Network Pharmacology
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Humans
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Kidney Failure, Chronic/metabolism*
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Medicine, Chinese Traditional
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China
3.Comparative Experimental Study of Nd∶YAG Laser Ablation of Fresh Isolated Pig Liver
Ruo-yu LIU ; Mu YUAN ; Hao LI ; Zi-yi ZHU ; Yu-lin TAN
Progress in Modern Biomedicine 2025;25(10):1613-1619,1657
Objective:To compare the characteristics and temperature changes of single and double fiber Nd∶YAG laser in fresh isolated pig liver,and to provide reference for clinical ablation treatment.Methods:Single-needle single-point and double-needle double-point ablations were perf ormed on fresh isolated pig livers using a 5 W power laser,and the morphology,range,and surrounding temperature changes of the ablation lesions caused by the two in vitro liver tissues were observed.Results:The ablation lesions were divided into carbonized area,necrotic area and deformed area from inside to outside.The carbonized area in the center of the ablation lesion in the double-fiber group was larger and the cell necrosis was more thorough.The aspect ratio(LD/TD)of the laser ablation lesion in the single-fiber group was larger than that in the double fiber group(P<0.001).The transverse diameter(TD)and volume(V)of the ablation lesion in the double-fiber group were larger than those in the single-fiber group(P<0.001).There was no significant difference in the longitudinal diameter(LD)of the ablation lesion between the double-fiber group and the single-fiber group(P>0.05).There was no significant difference in the temperature of 20 s,40 s and 60 s at 5 mm and 10 mm beside the ablation center between the two groups(all P>0.05).Conclusion:Under the condition of 5 W,the temperature changes around the single and double fiber ablation are similar.The single fiber is suitable for small tumor ablation,and the double fiber ablation range is larger,which can be used for one-time full coverage ablation of larger cancer nodules.
4.FTO regulates resistance of triple-negative breast cancer to adriamycin through Wnt/β-catenin signaling pathway
Jin-min WU ; Yu-hang QI ; Jing-yi FANG ; Wei-zhi MU ; Zhao-lin CHEN ; Zhao-yi YANG
Chinese Pharmacological Bulletin 2025;41(12):2334-2341
Aim To explore the effect of FTO on adria-mycin resistance in triple-negative breast cancer through the Wnt/β-catenin signaling pathway and to reveal the underlying mechanism.Methods The MDA-MB-231/ADR drug-resistant cell line was constructed using a method of gradually increasing adriamycin concentra-tion with intermittent induction.The half-inhibitory concentration(IC50)of adriamycin for MDA-MB-231 and MDA-MB-231/ADR cells and the expression of FTO were compared.After knocking down FTO in MDA-MB-231/ADR cells,CCK-8,qRT-PCR,colony formation assay,transwell,flow cytometry,and Western blot were used to assess the changes in the IC50 of adri-amycin,cell proliferation,migration,invasion,apopto-sis,and the expression of related proteins.Results FTO was highly expressed in MDA-MB-231/ADR cells.After FTO knockdown,the IC50 value of adriamy-cin in MDA-MB-231/ADR cells decreased,and the a-bilities of proliferation,migration and invasion were weakened.In the FTO knockdown group,the expres-sion levels of Bax,cleaved-caspase3,GSK-3 β proteins and the apoptosis rate significantly increased,while the expression levels of Bcl-2,Wnt5a,β-catenin,c-myc,cyclin D1,and P-gp proteins decreased.Conclusion FTO may inhibit the apoptosis of MDA-MB-231/ADR cells through the Wnt/β-catenin signaling pathway,al-ter P-gp expression,and thereby enhance the resistance of MDA-MB-231/ADR cells to adriamycin.
5.Chemical constituents from the leaves of Drynaria fortunei and their antioxidant activity
Xin CHEN ; Jia-cheng WANG ; Yan-yan LIU ; Yong-wen ZHANG ; Ze-jing MU ; Hai-yan ZHANG ; Yu PENG ; Tong-lin WAN ; Yong-hong LIANG
Chinese Traditional Patent Medicine 2025;47(8):2587-2592
AIM To study the chemical constituents from the leaves of Drynaria fortunei(Kunze)J.Sm.and their antioxidant activity.METHODS ODS-AG-HG,Sephadex LH-20 and semi-preparative HPLC were used for separation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant activity was determined by DPPH mothod.RESULTS Fifteen compounds were isolated and identified as kaempferol-3-O-neohesperidoside(1),dihydrodehydrodiconiferyl alcohol(2),kaempferol-3,7-di-O-α-L-rahmnoside(3),astragalin(4),loliolid(5),trichothecene analogue(6),2,2-[bis-4-(2,3-dihydroxypropoxy)phenyl]propane(7),maculatin(8),trichothecin(9),4-[(Z)-but-2-enoyloxy]-8-chloro-12-hydroxy-7,13-epoxytrichothec-9-ene(10),8-deoxy-trichotecin(11),β-sitosterol(12),daucosterol(13),afzelin(14),samwinol(15).The IC50 values of the leaf and rhizome extracts against DPPH free radicals were(0.072±0.005),(0.287±0.012)mg/mL,respectively.CONCLUSION Compounds 1,2,5-11,15 are isolated from this plant for the first time.The leaves of D.fortunei exhibit strong antioxidant activity.
6.Synthesis and Applications of Indole-3-formylhydrazine Modified Pyrene Schiff Base Compound as Copper Ion Fluorescence Probe
Mu-Xi WANG ; Zhen-Yu HUANG ; Xiao-Feng LIN ; Xiao-Lan LEI ; Jian SUN ; Li-Jun MA
Chinese Journal of Analytical Chemistry 2025;53(7):1108-1117
In this work,a fluorescent probe PIN was synthesized using indole-3-carbohydrazide and pyrenecarboxaldehyde as raw materials.PIN showed weak fluorescence emission in aqueous solution with acetonitrile volume fraction of 70%.However,when Cu2+was added to this aqueous solution of PIN,a new fluorescence emission peak appeared at 495 nm,and the intensity of this peak gradually increased with the increase of concentration of Cu2+,and also caused a significant change in the fluorescence color of the solution.In contrast,the addition of 15 kinds of other common metal ions did not cause such change.The detection limit of PIN for Cu2+was 78.7 nmol/L,which was much lower than the maximum permitting level of Cu2+in drinking water in hygienic standard for drinking water in China.Therefore,PIN was a highly selective and sensitive fluorescence-enhanced probe for Cu2+.Meanwhile,the addition of Cu2+could also cause a new absorption peak at 440 nm in the ultraviolet-visible absorption spectrum of the aqueous solution of PIN,and meanwhile the colorless PIN solution changed into yellow,exhibiting the performance of PIN as a colorimetric probe for Cu2+.By fitting with the Levenberg-Marquardt algorithm equation,the binding ratio of PIN to Cu2+was 2:1,and the binding constant was 3.42×1012 L2/mol2.In addition,the binding mode of PIN with Cu2+was explored by using proton nuclear magnetic resonance(1H NMR)titration experiments and density functional theory simulations.The results showed that the addition of Cu2+could cause the aggregation of PIN molecules to form excimers,thus showing highly selective recognition.Finally,PIN was made into a simple test strip,which could achieve rapid and convenient fluorescence detection of Cu2+in actual water samples.
7.MiR-708 expression and CXCL13 level in patients with acute myocardial infarction and their associa-tion
Chinese Journal of cardiovascular Rehabilitation Medicine 2025;34(3):299-304
Objective:To study microRNA-708(miR-708)expression and level of CXC chemokine ligand 13(CX-CL13)in patients with acute myocardial infarction(AMI)and their association.Methods:A total of 60 AMI pa-tients treated in Department of Cardiology,Shanghai Fengxian District Central Hospital between May 2020 and May 2023 were selected as AMI group,another 60 healthy subjects who simultaneously underwent physical examination were regarded as healthy control group.Serum miR-708 expression,levels of CXCL13,creatine kinase isoenzyme MB(CK-MB)and cardiac troponin I(cTnI)were measured.The association of miR-708,CXCL13 with CK-MB and cTnI in AMI patients was analyzed by Pearson correlation analysis.Receiver operating characteristic(ROC)curve was used to analyze diagnostic value of miR-708 and CXCL13 for AMI.Results:Compared with participants in the healthy control group,those in AMI group had significant lower miR-708 expression[(0.54±0.17)vs.(1.05±0.36)],and significant higher levels of CXCL13[(72.44±13.18)pg/ml vs.(48.16±5.72)pg/ml],cTnI[(6.07±2.12)ng/ml vs.(1.77±0.25)ng/ml]and CK-MB[(62.43±12.42)U/L vs.(14.35±3.61)U/L](P<0.001 all).Pearson correlation analysis revealed a significant inverse correlation of miR-708 expression with CXCL13,cTnI and CK-MB(r=-0.687,P<0.001;r=-0.559,P<0.001;r=-0.588,P<0.001);and a significant positive correlation of CXCL13 level with cTnI and CK-MB(r=0.598,P<0.001;r=0.580,P<0.001).ROC curve analysis indicated that the area under the curve(AUC)of miR-708 expression,CXCL13 level and their combination for diagnosing AMI was 0.833(95%0.753~0.912),0.844(95%0.766~0.922)and 0.946(95%0.897~0.995)respectively,and AUC of the combined detection was significantly higher than those of single detections(Z=2.353,2.162,P=0.019,0.031).Conclusion:The expression of miR-708 significantly decreases and CXCL13 level sig-nificantly increases in AMI patients.Their combined detection possess certain diagnostic value for AMI.
8.Comparative Experimental Study of Nd∶YAG Laser Ablation of Fresh Isolated Pig Liver
Ruo-yu LIU ; Mu YUAN ; Hao LI ; Zi-yi ZHU ; Yu-lin TAN
Progress in Modern Biomedicine 2025;25(10):1613-1619,1657
Objective:To compare the characteristics and temperature changes of single and double fiber Nd∶YAG laser in fresh isolated pig liver,and to provide reference for clinical ablation treatment.Methods:Single-needle single-point and double-needle double-point ablations were perf ormed on fresh isolated pig livers using a 5 W power laser,and the morphology,range,and surrounding temperature changes of the ablation lesions caused by the two in vitro liver tissues were observed.Results:The ablation lesions were divided into carbonized area,necrotic area and deformed area from inside to outside.The carbonized area in the center of the ablation lesion in the double-fiber group was larger and the cell necrosis was more thorough.The aspect ratio(LD/TD)of the laser ablation lesion in the single-fiber group was larger than that in the double fiber group(P<0.001).The transverse diameter(TD)and volume(V)of the ablation lesion in the double-fiber group were larger than those in the single-fiber group(P<0.001).There was no significant difference in the longitudinal diameter(LD)of the ablation lesion between the double-fiber group and the single-fiber group(P>0.05).There was no significant difference in the temperature of 20 s,40 s and 60 s at 5 mm and 10 mm beside the ablation center between the two groups(all P>0.05).Conclusion:Under the condition of 5 W,the temperature changes around the single and double fiber ablation are similar.The single fiber is suitable for small tumor ablation,and the double fiber ablation range is larger,which can be used for one-time full coverage ablation of larger cancer nodules.
9.FTO regulates resistance of triple-negative breast cancer to adriamycin through Wnt/β-catenin signaling pathway
Jin-min WU ; Yu-hang QI ; Jing-yi FANG ; Wei-zhi MU ; Zhao-lin CHEN ; Zhao-yi YANG
Chinese Pharmacological Bulletin 2025;41(12):2334-2341
Aim To explore the effect of FTO on adria-mycin resistance in triple-negative breast cancer through the Wnt/β-catenin signaling pathway and to reveal the underlying mechanism.Methods The MDA-MB-231/ADR drug-resistant cell line was constructed using a method of gradually increasing adriamycin concentra-tion with intermittent induction.The half-inhibitory concentration(IC50)of adriamycin for MDA-MB-231 and MDA-MB-231/ADR cells and the expression of FTO were compared.After knocking down FTO in MDA-MB-231/ADR cells,CCK-8,qRT-PCR,colony formation assay,transwell,flow cytometry,and Western blot were used to assess the changes in the IC50 of adri-amycin,cell proliferation,migration,invasion,apopto-sis,and the expression of related proteins.Results FTO was highly expressed in MDA-MB-231/ADR cells.After FTO knockdown,the IC50 value of adriamy-cin in MDA-MB-231/ADR cells decreased,and the a-bilities of proliferation,migration and invasion were weakened.In the FTO knockdown group,the expres-sion levels of Bax,cleaved-caspase3,GSK-3 β proteins and the apoptosis rate significantly increased,while the expression levels of Bcl-2,Wnt5a,β-catenin,c-myc,cyclin D1,and P-gp proteins decreased.Conclusion FTO may inhibit the apoptosis of MDA-MB-231/ADR cells through the Wnt/β-catenin signaling pathway,al-ter P-gp expression,and thereby enhance the resistance of MDA-MB-231/ADR cells to adriamycin.
10.MiR-708 expression and CXCL13 level in patients with acute myocardial infarction and their associa-tion
Chinese Journal of cardiovascular Rehabilitation Medicine 2025;34(3):299-304
Objective:To study microRNA-708(miR-708)expression and level of CXC chemokine ligand 13(CX-CL13)in patients with acute myocardial infarction(AMI)and their association.Methods:A total of 60 AMI pa-tients treated in Department of Cardiology,Shanghai Fengxian District Central Hospital between May 2020 and May 2023 were selected as AMI group,another 60 healthy subjects who simultaneously underwent physical examination were regarded as healthy control group.Serum miR-708 expression,levels of CXCL13,creatine kinase isoenzyme MB(CK-MB)and cardiac troponin I(cTnI)were measured.The association of miR-708,CXCL13 with CK-MB and cTnI in AMI patients was analyzed by Pearson correlation analysis.Receiver operating characteristic(ROC)curve was used to analyze diagnostic value of miR-708 and CXCL13 for AMI.Results:Compared with participants in the healthy control group,those in AMI group had significant lower miR-708 expression[(0.54±0.17)vs.(1.05±0.36)],and significant higher levels of CXCL13[(72.44±13.18)pg/ml vs.(48.16±5.72)pg/ml],cTnI[(6.07±2.12)ng/ml vs.(1.77±0.25)ng/ml]and CK-MB[(62.43±12.42)U/L vs.(14.35±3.61)U/L](P<0.001 all).Pearson correlation analysis revealed a significant inverse correlation of miR-708 expression with CXCL13,cTnI and CK-MB(r=-0.687,P<0.001;r=-0.559,P<0.001;r=-0.588,P<0.001);and a significant positive correlation of CXCL13 level with cTnI and CK-MB(r=0.598,P<0.001;r=0.580,P<0.001).ROC curve analysis indicated that the area under the curve(AUC)of miR-708 expression,CXCL13 level and their combination for diagnosing AMI was 0.833(95%0.753~0.912),0.844(95%0.766~0.922)and 0.946(95%0.897~0.995)respectively,and AUC of the combined detection was significantly higher than those of single detections(Z=2.353,2.162,P=0.019,0.031).Conclusion:The expression of miR-708 significantly decreases and CXCL13 level sig-nificantly increases in AMI patients.Their combined detection possess certain diagnostic value for AMI.

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