1.A study on CD90, IGF1R expression in hepatocellular carcinoma
Jian NIU ; Hewei ZHAO ; Suwen ZHENG ; Dongliang YAN ; Yewei ZHANG
Chinese Journal of General Surgery 2012;27(2):131-133
Objective To investigate the expression of CD90,IGF1R in hepatocellular carcinoma.Methods CD90,IGF1R expression were detected by SP immunohistochemical staining in 36 cases of hepatocellular carcinoma,20 cases of normal liver tissue biopsied from patients of chronic cholecystitis undergoing cholecystectomy. Results The positive rate of CD90 (63.89%,23/36),IGF1R (52.78%,19/36) in hepatocellular carcinoma significantly increased (P < 0.05 ); The positive rate of CD90 was higher in UICC Ⅲ - Ⅳ stage group (79.17% ) than in UICC stage Ⅰ - Ⅱ group (33.33%,P <0.05) ;The positive rate of CD90 was higher in low differentiated group (76.92% ) than in well-differentiated group (56.52%,P <0.05).The positive rate of IGF1R was higher in UICC Ⅲ - Ⅳ stage group (70.83% ) than in UICC stage Ⅰ - Ⅱ group ( 16.67%,P < 0.05 ). The positive rate of IGF1R was higher in low differentiated group (84.62%) than in well-differentiated group (37.38%,P < 0.05 ).The expression of IGF1R was positively correlated with that of CD90 (P < 0.05 ).The median survival of CD90+ patients (85 days) was shorter than CD90- patients ( 505 days ) ( P < 0.05 ).The median survival of IGF1 R + patients (100 days) was shorter than IGF1 R- patients (408 days,P < 0.05). Conclusions CD90 or IGF1R expression correlates positively with the progression of HCC.
2.Expressions of CD90 and hTERT in hepatocellular carcinoma and Their Clinical Significance
Yewei ZHANG ; Jian NIU ; Hewei ZHAO ; Wen WANG ; Dongliang YAN ; Xuehao WANG
Chinese Journal of Hepatobiliary Surgery 2012;18(1):37-39
ObjectiveTo study the expressions of CD90 and hTERT in hepatocellular carcinoma (HCC),and their relationships to progression of tumor.MethodsThe expressions of CD90 and hTERT in hepatocellular carcinoma were detected by S-P immunohistochemical staining.Twenty patients with hemangiomas of liver were used as control.ResultsCompared with the control group,the positive rates of CD90 and hTERT in HCC were significantly higher (63.9% and 47.2% vs 0% and 0%).The positive rates of CD90 and hTERT were significantly higher in patients with tumors at UICC Ⅲ-Ⅳ stage than at UICC stage Ⅰ -Ⅱ (79.1% and 62.5% vs 33.3% and 16.6%).The CD90 expression correlated with hTERT positively.There were significant differences in survival between patients with CD90+ and CD90- or hTERT+ and hTERT-.The median postoperative survivals for patients with CD90+ and hTERT+,CD90- and hTERT- were 85 d and 76 d,505 d and 463 d,respectively.ConclusionsCD90 expression correlated positively with progression of HCC.It has the potential to serve as a prognostic marker for HCC.
3.The characteristic analysis on intestinal metabolism of Pueraria lobata (Willd.)Ohwi
Hewei LI ; Tong ZHAO ; Ling DONG ; Gang WANG ; Honghuan DONG ; Yanjiang QIAO
International Journal of Traditional Chinese Medicine 2014;36(2):131-134
Objective To establish a method to compare the difference of exposure component of oral taking different part ofPueraria Lobata (Willd.) Ohwi in intestine.Methods After the incubation of puerarin,extraction Radix Puerariae and Flos Puerariae with S9,the mixtures were centrifuged to get the supernatant for analysis with HPLC.Results The research showed that the metabolic rate of puerarin was higher than that of extractions because of the concentration of enzyme.The difference between the fingerprints of Radix Puerariae and Flos Puerariae Lobata indicated that there was a difference of chemical components in such two parts of Kudzuvine Root.Conclusion The profile of intestinal metabolism can be revealed in the research of gut wall metabolism in the course of intestinal absorption by S9 incubation.
4.Antibody-directed lentiviral vector-mediated hepatocarcinoma cells targeting IGF1R- siRNA/P53 genes therapy
Jian NIU ; Hewei ZHAO ; Wen WANG ; Bin YU ; Bin LIU ; Xuehao WANG ; Yewei ZHANG
Chinese Journal of Hepatobiliary Surgery 2012;18(5):372-376
ObjectiveTo investigate the targeting infection of single chain antibody againstAFP (scFv anti-AFP) directed lentivirus and the inhibitory effects of a dual-growth inhibition systemon hepatocarcinoma cells.MethodsPlasmids WtP53-pPRIME-miR30-shRNA-IGF1R,pMD2G-Anti-AFP,and psPAX2 have previously been constructed to cotransfect to the packaging cell line 293Tusing Lipofectamine2000.The infection results were observed through fluorescence microscopy.PCRand Western blotting were used to demonstrate the successful transduction and transcription of theWtP53-pPRIME-miR30-shRNA-IGF1R gene.The effects of reconstructed lentivirus infected liver cellgrowth were assessed by the cell growth curve of CCK8 cells. Apoptosis was evaluated by theTUNEL assay.ResultsRecombined lentivirus was successfully constructed with the functional PFUtiters of recombined lentivirus at 4.58× 109PFU/ml.This positive result was confirmed by PCR andWestern blotting.ConclusionsThe targeted therapy mediated by anti-AFP scFv could significantlyinhibit the proliferation of HEP3B cells and promote the apoptosis.
5.Mechanism of action of dysregulated mitochondrial quality control system mediating Parkinson's disease
Juan LIU ; Yanjie LI ; Hewei QIN ; Luyao MA ; Nannan ZHAO ; Huimin DING
The Journal of Practical Medicine 2024;40(11):1479-1482
Parkinson's disease(PD)is a common neurodegenerative disease with a complex pathogenesis,and a large number of studies have shown that mitochondrial dysfunction is an important causative factor for PD,whereas dysregulation of mitochondrial quality control is a key factor leading to mitochondrial dysfunction,and that aberrant mitochondrial biogenesis,fusion/fission imbalance,and mitochondrial hyperautophagy are closely associated with the onset of PD,but the role of the mitochondrial quality control system in the progression of PD is unclear.Therefore,this paper reviews the mechanism of mitochondrial quality control system in PD,with the aim of providing new ideas and theoretical basis for the clinical prevention and treatment of PD.
6.Advances in the mechanism-of-action of circRNA in Parkinson's disease
Juan LIU ; Yanjie LI ; Hewei QIN ; Luyao MA ; Nannan ZHAO ; Zhenhua XU
Chinese Journal of Comparative Medicine 2024;34(2):161-166
PD is a neurodegenerative disease characterized by degenerative death of dopaminergic neurons in the substantia nigra,exhibiting a range of motor and non-motor symptoms with serious effects on quality of life.circRNA is a covalently closed-loop non-coding RNA that plays a major role in PD progression.This article reviews the involvement of circRNA in oxidative stress,regulation of transcription,neuroinflammation,autophagy,and α-synuclein.
7.Jiawei Chunze Decoction treats urinary retention after spinal cord injury in rats based on the regulation of endoplasmic reticulum stress apoptosis
Bochao ZHU ; Yanjie LI ; Hewei QIN ; Nannan ZHAO ; Haoyuan LIU ; Zhenhua XU ; Yupu WANG
Chinese Journal of Tissue Engineering Research 2025;29(2):371-378
BACKGROUND:Preliminary clinical observations found that Jiawei Chunze Decoction is an effective formula for clinical treatment of urinary retention after spinal cord injury.Animal experiments have found that the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway is closely related to the degree of bladder dysfunction. OBJECTIVE:To further investigate the effects of Jiawei Chunze Decoction on bladder function and PI3K/Akt signaling pathway in rats with urinary retention. METHODS:Sixty female Sprague-Dawley rats were randomly divided into sham operation group,model group,Jiawei Chunze Decoction low-dose group,Jiawei Chunze Decoction high-dose group and agonist group.In the sham operation group,the spinal cord was exposed but not transected.In the other groups,the modified Hassan Shaker spinal cord transection method was used to prepare the model of sacral medullary injury.At 24 hours after modeling,the sham operation group and model group were intragastrically given equal volume of normal saline,Jiawei Chunze Decoction low-dose and high-dose groups were given Jiawei Chunze Decoction granules containing 14.4 and 28.8 g/kg,respectively,via intragastric administration for 4 weeks,and the agonist group was treated with an intraperitoneal injection of PI3K/Akt signaling pathway agonist 740Y-P at a dose of 0.02 mg/kg.After 4 weeks of treatment,the maximum bladder capacity,leakage point pressure and bladder compliance of rats in each group were detected by urine flow dynamics.The minimum bladder contraction tension and frequency of rats in each group were detected by detrusor pull test.The pathological changes of the rat bladder in each group were observed by hematoxylin-eosin staining.The concentrations of GRP78,CHOP and Caspase-12 in serum were detected by ELISA,and the mRNA and protein expressions of PI3K,Akt,GRP78,CHOP and Caspase-12 in bladder tissues were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the sham operation group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats in the model group were increased(P<0.05),and the leakage point pressure and bladder contraction frequency were decreased(P<0.05);serum GRP78,CHOP,and Caspase-12 levels were also increased(P<0.05).The arrangement of bladder epithelial cells in the model group was disordered,and there was monocyte infiltration between cells,tissue edema,and detrusor tract atrophy.The mRNA and protein expressions of PI3K and Akt in bladder tissues were significantly decreased in the model group compared with the sham operation group,while those of GRP78,CHOP and Caspase-12 were increased(P<0.05).Compared with the model group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats were decreased in the Jiawei Chunze Decoction low-dose,high-dose and agonist groups after 4 weeks of intervention(P<0.05),while the leakage point pressure and bladder contraction frequency were increased(P<0.05);serum GRP78,CHOP,Caspase-12 levels were decreased(P<0.05).The bladder epithelial cells in the three intervention groups were distributed evenly,arranged neatly,with less inflammatory cell infiltration and fuller detrusor muscle bundle.Compared with the model group,the mRNA and protein expressions of PI3K and Akt were increased in the three intervention groups,while those of GRP78,CHOP and Caspase-12 were decreased(P<0.05).The Jiawei Chunze Decoction high-dose group was better than the Jiawei Chunze Decoction low-dose group and shared the similar results with the agonist group.To conclude,Jiawei Chunze Decoction can improve the bladder function of rats with urinary retention after spinal cord injury,and the mechanism may be related to reducing the occurrence of endoplasmic reticulum stress in bladder tissue through the PI3K/Akt signaling pathway,and then alleviating apoptosis.
8.Role of Autophagy in Cardiovascular Diseases and Traditional Chinese Medicine Treatment: A Review
Yiting ZHAO ; Hewei QIN ; Xia WEI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):284-292
Cardiovascular diseases, a group of major non-infectious diseases, are characterized by high morbidity and mortality, significantly influencing patients' quality of life. Hence, it is imperative to discover a secure and efficacious treatment approach. As a form of programmed cell death, autophagy has been demonstrated to be associated with the pathogeneses of hypertension, diabetic cardiomyopathy, myocardial ischemia-reperfusion injury, heart failure, atherosclerosis, and other cardiovascular disorders. It serves as one of the potential targets for the clinical intervention in cardiovascular diseases by traditional Chinese medicine (TCM). Autophagy exerts dual regulatory effects on the occurrence and development of cardiovascular diseases, and its specific effect predominantly depends on the extent of autophagy and the pathological stage of diseases. Recent studies have confirmed that TCM can prevent and treat cardiovascular diseases by directly regulating autophagy or interacting with oxidative stress, inflammation, and apoptosis under the regulation of autophagy, exhibiting the unique advantages of multiple targets, multiple components, and mild adverse reactions. This article reviews the experimental research progress in the role of autophagy and the intervention by active components and compound prescriptions of TCM and Chinese patent medicines in common cardiovascular diseases (such as diabetic cardiomyopathy, myocardial ischemia-reperfusion injury, heart failure, and atherosclerosis) in recent years and summarizes the research shortcomings, providing a theoretical basis and strategies for the clinical treatment of cardiovascular diseases.
9.Role of Autophagy in Cardiovascular Diseases and Traditional Chinese Medicine Treatment: A Review
Yiting ZHAO ; Hewei QIN ; Xia WEI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):284-292
Cardiovascular diseases, a group of major non-infectious diseases, are characterized by high morbidity and mortality, significantly influencing patients' quality of life. Hence, it is imperative to discover a secure and efficacious treatment approach. As a form of programmed cell death, autophagy has been demonstrated to be associated with the pathogeneses of hypertension, diabetic cardiomyopathy, myocardial ischemia-reperfusion injury, heart failure, atherosclerosis, and other cardiovascular disorders. It serves as one of the potential targets for the clinical intervention in cardiovascular diseases by traditional Chinese medicine (TCM). Autophagy exerts dual regulatory effects on the occurrence and development of cardiovascular diseases, and its specific effect predominantly depends on the extent of autophagy and the pathological stage of diseases. Recent studies have confirmed that TCM can prevent and treat cardiovascular diseases by directly regulating autophagy or interacting with oxidative stress, inflammation, and apoptosis under the regulation of autophagy, exhibiting the unique advantages of multiple targets, multiple components, and mild adverse reactions. This article reviews the experimental research progress in the role of autophagy and the intervention by active components and compound prescriptions of TCM and Chinese patent medicines in common cardiovascular diseases (such as diabetic cardiomyopathy, myocardial ischemia-reperfusion injury, heart failure, and atherosclerosis) in recent years and summarizes the research shortcomings, providing a theoretical basis and strategies for the clinical treatment of cardiovascular diseases.
10.Changes in ferroptosis in hippocampal neurons of vascular dementia model rats treated with Tongmai Kaiqiao Pill
Nannan ZHAO ; Yanjie LI ; Hewei QIN ; Bochao ZHU ; Huimin DING ; Zhenhua XU
Chinese Journal of Tissue Engineering Research 2025;29(7):1401-1407
BACKGROUND:Research has demonstrated a close association between ferroptosis and vascular dementia.Tongmai Kaiqiao Pill has a certain effect on improving the cognitive function of vascular dementia patients,but its mechanism is unclear. OBJECTIVE:To explore the interventional effects and molecular mechanisms of Tongmai Kaiqiao Pill for vascular dementia based on the regulation of ferroptosis by the nuclear factor erythroid-2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4)signaling pathway. METHODS:Among eighty-four SD male rats,12 rats were used as the sham-operated group,and the rest of them were prepared as a model of vascular dementia by the modified 2-VO method,and then randomly divided into the model group,the Tongmai Kaiqiao Pills high-,moderate-,and low-dosage(27.6,13.8,and 6.9 g/kg)groups,the combined group(Tongmai Kaiqiao Pill high-dosage+ML385,20 mg/kg),and the donepezil hydrochloride group(0.45 mg/kg).The drug was given once a day by intragastric administration.The combined group was also intraperitoneally injected Nrf2 inhibitor ML385,once a day,for 4 weeks.Morris water maze was used to detect the learning memory ability of rats.Hematoxylin-eosin staining was used to observe the histopathological changes in the hippocampus of rats in each group.Colorimetric assay was used to detect the content of reduced glutathione,ferrous ion(Fe2+),and malondialdehyde in the serum of rats.Prussian blue staining was used to detect the iron deposition in the hippocampal tissue of rats.Transmission electron microscopy was used to observe the ultrastructural changes of mitochondria in rat hippocampal tissues.Western blot assay was used to detect the protein expression levels of Nrf2,HO-1,GPX4,XCT,and ferritin heavy chain 1(FTH1)in rat hippocampal tissues. RESULTS AND CONCLUSION:(1)In comparison to the sham operation,rats in the model group exhibited a significantly prolonged latency period(P<0.05)and a reduced number of platform crossings(P<0.05).Additionally,the hippocampal tissues of these rats displayed loosely organized structure,deeply stained cell nuclei,and solidified or lysed chromatin.Ferri ions aggregated in CA1 region.There were atrophied mitochondria with dissolved cristae and thickened mitochondrial membranes.Fe2+,malondialdehyde,and reduced glutathione levels in rat serum were found to be elevated(P<0.05).A significant reduction in the expression of GPX4,HO-1,XCT,Nrf2,and FTH1 proteins was detected in the hippocampus(P<0.05).(2)Compared to the model group,the average escape latency of the rats was significantly reduced following intervention with Tongmai Kaiqiao Pills and donepezil hydrochloride(P<0.05),with an increased number of platform crossings(P<0.05).Hippocampal neurons showed significant recovery.Notably,iron aggregation in the CA1 region was significantly reduced,and mitochondrial structure and function were improved.There were significant reductions in Fe2+and malondialdehyde levels,while the levels of GPX4,HO-1,XCT,Nrf2,and FTH1 in rat hippocampal tissues,and reduced glutathione in serum were significantly increased(P<0.05).(3)The high-dose Tongmai Kaiqiao Pills exhibited a treatment effect comparable to that of donepezil hydrochloride(P>0.05),with a significant prolongation of water maze escape latency(P<0.05),a reduced number of platform crossings(P<0.05),and insignificant neuronal pathological changes in the CA1 area.However,the combined group showed increased iron deposition,elevated malondialdehyde and Fe2+levels in blood serum(P<0.05),reduced glutathione content(P<0.05),hippocampal tissue mitochondrial atrophy,and reduced expression of Nrf2,XCT,HO-1,GPX4,and FTH1 proteins(P<0.05).Within a certain range,higher doses of Tongmai Kaiqiao Pills demonstrated a more pronounced effect,comparable to the efficacy of high-dose donepezil hydrochloride.(4)It is concluded that Tongmai Kaiqiao Pills have been shown to mitigate histopathological changes in the rat hippocampus and enhance cognitive function in rats with vascular dementia.The mechanism of action is likely associated with the suppression of ferroptosis through the activation of the Nrf2/HO-1/GPX4 signaling pathway.