1.Animal experimental study of FAPI molecular imaging in cardiac pressure overload-unloading process
Guokun WANG ; Qinqin YANG ; Zhenyu ZENG ; Xiu LUO ; Siyu LIANG ; Changjing ZUO ; Chao CHENG ; Suxuan LIU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(11):655-660
Objective:To investigate the utility of 68Ga-fibroblast activation protein (FAP) inhibitor (FAPI)-04 PET imaging in assessing the therapeutic response in pressure overload-induced heart failure. Methods:Rat models of pressure overload-induced heart failure were established by abdominal aortic constriction (AAC). Thirty rats were categorized into AAC group, 7 days reverse AAC (rAAC) group, and sham operation (sham) group ( n=10 per group) using completely random grouping method. All rats underwent 68Ga-FAPI-04 PET/CT imaging at 4 and 8 weeks after the ACC operation, while echocardiography, pathological examination, and immunohistochemical analysis were performed at 8 weeks postoperation. One-way analysis of variance, independent-sample t test and Pearson correlation analysis were used for data analysis. Results:68Ga-FAPI-04 PET/CT imaging showed that the target-to-background ratios of the heart and liver had significant differences among three groups both at 4 and 8 weeks postoperation ( F values: 2 547.12, 2 041.71, 462.65, 1 210.97, all P<0.001). Echocardiography revealed left ventricular ejection fraction (LVEF), left ventricular internal diameter at end-diastole (LVIDd), and left ventricular internal diameter at end-systole (LVIDs) in three groups at 8 weeks postoperation were significantly different ( F values: 118.92, 9.11, 10.63, all P<0.01). Rats were sacrificed at 8 weeks postoperation, and Masson staining showed that the fibrosis in the heart and liver of the rAAC group was significantly improved compared with that of the AAC group, and immunohistochemical analysis revealed significantly lower FAP levels in the heart and liver of the rAAC group compared with those of the AAC group ( t values: from -11.27 to -4.16, all P<0.01). FAPI uptake in the heart of the AAC group and rAAC group at 8 weeks postoperation were significantly positively correlated with FAPI uptake in the liver, LVIDd and LVIDs, FAPI uptake in the heart was significantly negatively correlated with LVEF, and FAPI uptake in the heart and liver were significantly positively correlated with fibrosis degree and FAP levels of corresponding organs ( r values: -0.89, -0.88, 0.72-0.97, all P<0.05). Conclusions:68Ga-FAPI-04 PET/CT can show the improvement process of cardio-liver fibrosis following the unloading of excessive pressure in heart failure. Myocardial FAPI uptake is closely related to the extent of heart failure improvement.
2.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
3.Study on the feasibility of low-dose chest CT combined with deep learning reconstruction algorithm in the diagnosis of pediatric mycoplasma pneumonia
Xiu CHENG ; Guihua LIU ; Sirun YU ; Dehong WU ; Wen CHEN ; Guan WANG ; Chao LIU
China Medical Equipment 2024;21(6):12-17
Objective:To explore the feasibility of 60 kV low-dose scanning technique on chest combined with ClearInfinity deep learning reconstruction algorithm in the diagnosis of pediatric mycoplasma pneumonia.Methods:A total of 132 pediatric patients,who admitted to Taihe Hospital Affiliated to Hubei Medical College and were diagnosed as mycoplasma pneumonia,were selected,and all of them underwent computed tomography(CT)scans on chest.They were randomly divided into routine dose group(66 cases),low dose ClearView and ClearInfinity group(66 cases).In the routine dose group,the tube voltage of CT scan on chest was 100 kV,and 50%ClearView iterative algorithm was adopted in this group.The tube voltage of CT scan on chest was 60kV in low dose ClearView and ClearInfinity group,and 50%ClearView iterative algorithm and 50%ClearInfinity deep learning reconstruction algorithm were used respectively to conduct reconstruction.The difference of radiation dose among the three groups was compared.The CT values and standard deviation(SD)values,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of the region of interest(ROI)of the images of 3 groups were measured and calculated.The images were subjectively evaluated by two diagnostic attending physicians with 10 years of work experience,and the Kappa test was adopted to analyze the consistency of the score results.Results:Compared with the routine dose group,the volume CT dose index(CTDIvol)values,dose-length product(DLP)values and effective radiation dose(ED)values of the low dose ClearView group and ClearInfinity group reduced respectively by 87.58%,87.24%and 88.00%,and the differences were statistically significant(t=4 584.07,63.73,61.27,P<0.01).The noise values of left and right lung of the routine dose group were significantly lower than those of the low dose ClearView group,while were significantly higher than those of ClearInfinity group,and the differences were significant(Z=-9.912,-7.013,P<0.01),and the difference of them between low dose ClearView group and ClearInfinity group was significant(Z=-9.912,P<0.01).The SNR and CNR of left and right lung of low dose ClearView group were significantly lower than those of the routine dose group,with statistically significant(t=-34.810,5.522,P<0.01),while these of the low dose ClearInfinity group were significant higher than them of the routine dose group(t=3.544,-8.674,P<0.05),respectively.The two attending physicians had favorable consistency in the subjective evaluation for images(Kappa>0.75,P<0.01).The subjective score of the routine dose group was not significantly different with that of the low dose ClearInfinity group(P>0.05),but was significantly better than that of the low dose ClearView group(Z=-6.425,P<0.01).Conclusion:For pediatric patients with mycoplasma pneumonia,the 60 kV low dose CT on chest combined with ClearInfinity deep learning reconstruction algorithm can ensure image quality on the premise of reducing radiation,which can ensure the diagnostic effect.
4.Study on learning curve of Da Vinci robotic segmentectomy
Boxiao HU ; Shiguang XU ; Bo LIU ; Wei XU ; Qiong WU ; Xingchi LIU ; Renquan DING ; Yuchi XIU ; Ming CHENG ; Shumin WANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(05):689-694
Objective To analyze the learning curve of Da Vinci robotic segmentectomy. Methods Cumulative sum analysis (CUSUM) was used to analyze the learning curve of Da Vinci robotic segmentectomy performed by the General Hospital of Northern Theater Command from February 2018 to December 2020. The learning curve was obtained by fitting, and R2 was used to judge the goodness of fitting. The clinical data of patients in different stages of learning curve were compared and analyzed. Results The first 50 patients who received Da Vinci robotic segmentectomy were included, including 24 males and 26 females, with an average age of 61.9±10.6 years. The operation time decreased gradually with the accumulation of operation patients. The goodness of fitting coefficient reached the maximum value when R2=0.907 (P<0.001), CUSUM (n) =0.009×n3−0.953×n2+24.968×n−7.033 (n was the number of patients). The fitting curve achieved vertex crossing when the number of patients reached 17. Based on this, 50 patients were divided into two stages: a learning and improving stage and a mastering stage. There were statistical differences in the operation time, intraoperative blood loss, postoperative drainage volume, number of lymph node dissection, postoperative catheter time, postoperative hospital stay, and postoperative complications between the two stages (P<0.05). Conclusion It shows that the technical competency for assuring feasible perioperative outcomes can be achieved when the cumulative number of surgical patients reaches 17.
5.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.
6.Data Mining of Medication Rules for the Treatment of Atopic Dermatitis the Children by Chinese Medical Master XUAN Guo-Wei
Jin-Dian DONG ; Cheng-Cheng GE ; Yue PEI ; Shu-Qing XIONG ; Jia-Fen LIANG ; Qin LIU ; Xiu-Mei MO ; Hong-Yi LI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):752-758
Objective Data mining technology was used to mine the medication rules of the prescriptions used in the treatment of pediatric atopic dermatitis by Chinese medical master XUAN Guo-Wei.Methods The medical records of effective cases of pediatric atopic dermatitis treated by Professor XUAN Guo-Wei at outpatient clinic were collected,and then the medical data were statistically analyzed using frequency statistics,association rule analysis and cluster analysis.Results A total of 242 prescriptions were included,involving 101 Chinese medicinals.There were 23 commonly-used herbs,and the 16 high-frequency herbs(frequency>100 times)were Glycyrrhizae Radix et Rhizoma,Saposhnikoviae Radix,Glehniae Radix,Perillae Folium,Ophiopogonis Radix,Cynanchi Paniculati Radix et Rhizoma,Microctis Folium,Dictamni Cortex,Scrophulariae Radix,Coicis Semen,Cicadae Periostracum,Lilii Bulbus,Rehmanniae Radix,Kochiae Fructus,Sclerotium Poriae Pararadicis,and Euryales Semen.The analysis of the medicinal properties showed that most of the herbs were sweet and cold,and mainly had the meridian tropism of the spleen,stomach and liver meridians.The association rule analysis yielded 24 commonly-used drug combinations and 20 association rules.Cluster analysis yielded 2 core drug combinations.Conclusion For the treatment of pediatric atopic dermatitis,Professor XUAN Guo-Wei focuses on the clearing,supplementing and harmonizing therapies,and the medication principle of"supporting the healthy-qi to eliminate the pathogen,and balancing the yin and yang"is applied throughout the treatment.
7.Protective Effect of Flos Puerariae,Hoveniae Semen, and Their Compatibility on Acute Alcoholic Gastric Mucosal Injury in Mice and Mechanism
Wenyong LIAO ; Muyun LI ; Xiao DONG ; Can CAO ; Min HUO ; Yuna REN ; Haiyan LIU ; Linlin XIU ; Cheng HE ; Angran FAN ; Shaohong CHEN ; Gansheng ZHONG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(10):39-47
ObjectiveTo explore the improvement effect of Flos Puerariae, Hoveniae Semen, and their compatibility on acute alcoholic gastric mucosal injury, and lay a foundation for further development of Flos Puerariae, Hoveniae Semen, and their compatibility in the prevention and treatment of alcohol-induced multiple organ injury. MethodThe acute alcohol-induced gastric mucosal injury model of mice was established by multiple intragastric administration of 56% Hongxing Erguotou liquor (15 mL·kg-1). A total of 120 male ICR mice were randomly divided into 8 groups, namely, the blank group, model group, omeprazole group (0.026 g·kg-1), Flos Puerariae-Hoveniae Semen (compatibility) high, medium, and low-dose groups (29.2,14.6, 7.3 g·kg-1), Flos Puerariae group (19.5 g·kg-1), and Hoveniae Semen group (19.5 g·kg-1), with 15 mice in each group. After one week of adaptive feeding, the animals were pre-administrated with the corresponding drug at the rate of 10 mL·kg-1 for 3 d. From the 4th day, after 1 h of administration, Erguotou liquid was administrated at the rate of 15 mL·kg-1 and the blank group was administrated with the same volume of deionized water to record the drunkenness and sober up time. The administration was lasted for 3 d. One hour after the last administration, the eyeballs were removed and the mice were sacrificed. The concentration of ethanol in serum was determined by gas chromatograph, and the activity of ethanol dehydrogenase (ADH) in gastric mucosa was determined by ultraviolet-vis spectrophotometer. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in gastric mucosa. Serum inflammatory factors were determined by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of nuclear transcription factor-κB (NF-κB) p65 and NF-κB inhibitory protein α (IκBα) were detected by real-time polymerase chain reaction (Real-time PCR). ResultAs compared with the normal group, the content of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in serum of mice in the model group was increased (P<0.05), the mRNA expression of NF-κB p65 in gastric mucosa tissues was increased (P<0.01), and the mRNA expression of IκBα was decreased (P<0.01). As compared with the model group, the drunkenness time of the omeprazole group, high and medium-dose compatibility groups, and Flos Puerariae group was prolonged (P<0.05), the sober up time of the high and medium-dose compatibility groups was shortened (P<0.05), the ethanol concentration in the serum of the high-dose compatibility group was decreased (P<0.05), the ADH activity in the gastric mucosa of the omeprazole group and high and medium-dose compatibility groups was increased (P<0.05), the macroscopic injury score of the high, medium, and low-dose compatibility groups and Flos Puerariae group was decreased (P<0.05), the score of pathological injury in the omeprazole group, high, medium, and low-dose compatibility groups, and Flos Puerariae group was decreased (P<0.01), the expression of IL-6 in serum of all drug groups was decreased (P<0.05), the expression of IL-1β in serum of the omeprazole group, high, medium, and low-dose Flos Puerariae groups, and Hoveniae Semen group was decreased (P<0.05), the expression of TNF-α in serum of high and medium-dose groups was decreased (P<0.05), the mRNA expression of NF-κB p65 in gastric mucosa tissues of all drug groups was decreased (P<0.05), and the mRNA expression of IκBα in gastric mucosa tissues of the omeprazole group and high, medium, and low-dose compatibility groups was increased (P<0.05). As compared with the high-dose compatibility group, the drunkenness time in the low-dose compatibility group and Hoveniae Semen group was shortened (P<0.01), the sober up time in the Flos Puerariae and Hoveniae Semen groups was prolonged (P<0.01), the concentration of ethanol in the serum of the medium and low-dose compatibility groups, Flos Puerariae group, and Hoveniae Semen group increased (P<0.05), the macroscopic injury score of the medium and low-dose compatibility groups and Hoveniae Semen group was increased (P<0.05), the pathological injury score of the medium and low-dose compatibility groups, Flos Puerariae group, and Hoveniae Semen group was increased (P<0.01), the content of IL-1β in serum of low-dose compatibility group, Flos Puerariae group, and Hoveniae Semen group was increased (P<0.01), and the mRNA expression of IκBα in gastric mucosa of the Flos Puerariae group and Hoveniae Semen group was decreased (P<0.05). As compared with the medium-dose compatibility group, the drunkenness time in the Hoveniae Semen group was shortened (P<0.05), the sober up time in the Flos Puerariae group was prolonged (P<0.05), the pathological injury score in the Flos Puerariae group and Hoveniae Semen group was increased (P<0.01), and the content of IL-1β in serum of the low-dose compatibility group, the Flos Puerariae group, and Hoveniae Semen group was increased (P<0.05). As compared with the low-dose compatibility group, the pathological injury score of the Hoveniae Semen group was increased (P<0.05). ConclusionFlos Puerariae, Hoveniae Semen, and their compatibility play a role in preventing and treating acute alcoholic gastric mucosal injury in mice, which may be related to the inhibition of the expression of NF-κB signal pathway in gastric mucosa, and the high-dose compatibility group has the optimal effect.
8.Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor.
Jia-Cheng SHEN ; Qin QI ; Dong HAN ; Yuan LU ; Rong HUANG ; Yi ZHU ; Lin-Shan ZHANG ; Xiu-di QIN ; Fang ZHANG ; Huan-Gan WU ; Hui-Rong LIU
Journal of Integrative Medicine 2023;21(2):194-204
OBJECTIVE:
This study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn's disease (CD) regulated by moxibustion through bile acid (BA) enterohepatic circulation and intestinal farnesoid X receptor (FXR).
METHODS:
Sprague-Dawley rats were randomly divided into control group, CD model group, mild moxibustion group and herb-partitioned moxibustion group. CD model rats induced by 2,4,6-trinitrobenzene sulfonic acid were treated with mild moxibustion or herb-partitioned moxibustion at Tianshu (ST25) and Qihai (CV6). The changes in CD symptoms were rated according to the disease activity index score, the serum and colon tissues of rats were collected, and the pathological changes in colon tissues were observed via histopathology. Western blot, immunohistochemistry (IHC) and immunofluorescence were used to evaluate the improvement of moxibustion on intestinal inflammation and mucosal barrier in CD by the BA-FXR pathway.
RESULTS:
Mild moxibustion and herb-partitioned moxibustion improved the symptoms of CD, inhibited inflammation and repaired mucosal damage to the colon in CD rats. Meanwhile, moxibustion could improve the abnormal expression of BA in the colon, liver and serum, downregulate the expression of interferon-γ and upregulate the expression of FXR mRNA, and inhibit Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) mRNA. The IHC results showed that moxibustion could upregulate the expression of FXR and mucin2 and inhibit TLR4 expression. Western blot showed that moxibustion inhibited the protein expression of TLR4 and MyD88 and upregulated the expression of FXR. Immunofluorescence image analysis showed that moxibustion increased the colocalization sites and intensity of FXR with TLR4 or nuclear factor-κB p65. In particular, herb-partitioned moxibustion has more advantages in improving BA and upregulating FXR and TLR4 in the colon.
CONCLUSION
Mild moxibustion and herb-partitioned moxibustion can improve CD by regulating the enterohepatic circulation stability of BA, activating colonic FXR, regulating the TLR4/MyD88 pathway, inhibiting intestinal inflammation and repairing the intestinal mucosal barrier. Herb-partitioned moxibustion seems to have more advantages in regulating BA enterohepatic circulation and FXR activation. Please cite this article as: Shen JC, Qi Q, Han D, Lu Y, Huang R, Zhu Y, Zhang LS, Qin XD, Zhang F, Wu HG, Liu HR. Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor. J Integr Med. 2023; 21(2): 194-204.
Rats
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Animals
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Crohn Disease/pathology*
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Moxibustion/methods*
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Toll-Like Receptor 4/metabolism*
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Rats, Sprague-Dawley
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Myeloid Differentiation Factor 88/metabolism*
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Colitis
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Inflammation
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Enterohepatic Circulation
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RNA, Messenger/metabolism*
9. Mechanism of nitidine chloride inducing apoptosis of cervical cancer cells by inhibiting p53 ubiquitination degradation
Zhong-Xiu SHI ; Yong HUANG ; Huan-Huan ZHAO ; Lin-Sen YANG ; Yong-Bin LIU ; Cheng-Cheng WANG ; Wei LI
Chinese Pharmacological Bulletin 2023;39(10):1891-1899
Aim To investigate the effect of nitidine chloride (NC) on the apoptosis of cervical cancer cells and its mechanism. Methods Cervical cancer cell lines HeLa and SiHa were selected as subjects. The cytotoxicity of NC and its inhibitory effect on cell growth were detected by CCK-8 assay and clone formation assay. The effect of NC on the apoptosis of cervical cancer cells was detected by TUNEL assay, and the expression of apoptosis-related proteins was detected by Western blot. The effects of NC on the interaction between p53 and E6AP protein, the level of p53 ubiquitination modification and the stability of p53 protein in cervical cancer cells were analyzed by immunoprecipi-tation assay, ubiquitination assay and Western blot assay. Results NC could significantly inhibit the proliferation and induce apoptosis of cervical cancer cells. NC could inhibit the interaction between tumor suppressor protein p53 and E6AP in cervical cancer cells, reduce the level of p53 ubiquitination modification, delay the degradation of p53 and increase the expression level of p53 protein. Conclusions NC can inhibit the ubiquitination and degradation of p53, improve the expression level of p53 protein, restore its tumor suppressor function, and thus play an anti -cervical cancer role.
10. The synergistic effect of withaferin A combined with cisplatin on cervical cancer and its mechanism
Wei LI ; Zhong-Xiu SHI ; Yong HUANG ; Zhi-Ying CHENG ; Jia-Hui DONG ; Qing-Qing LONG ; Shan HE ; Tao LIU ; Cheng-Cheng WANG
Chinese Pharmacological Bulletin 2023;39(6):1127-1135
Aim To study the synergistic effect of withaferin A (WA) combined with cisplatin (DDP) on cervical cancer and its mechanism. Methods MTT assay was employed to detect the synergistic effect of WA on DDP in cervical cancer cell lines. Annexin V-FITC/PI staining, TUNEL assay and immunoblotting were used to investigate the effect of WA combined with DDP on apoptosis of cervical cancer cells. Immunofluorescence and immunoblotting were used to detect NF-kB/MDR1 pathway related proteins. DCFH-DA and MitoSOX were applied to determine the intracellular reactive oxygen species (ROS) levels. A xenograft model was also used to evaluate the synergistic effect of WA on DDP. Results The combination of WA and DDP could inhibit the survival of cervical cancer cells, promote apoptosis, and inhibit the growth of tumor in mice. WA could inhibit DDP-induced NF-kB/MDR1 signaling pathway and promote ROS production. Conclusions WA plays a synergistic role in anti-cervical cancer by inhibiting DDP-induced NF-kB/MDR1 pathway activation and enhancing DDP induced ROS production.

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