1.The mechanisms of paeonol reversing multidrug resistance in ovarian cancer SKOV3/DDP cells
Li HAN ; Xiao-juan GUO ; Zhong CHEN ; Hua BIAN ; Chao-yun ZHANG ; Wen-hua ZANG ; Qian WANG ; Jiu-lue HU
Acta Pharmaceutica Sinica 2018;53(9):1511-1517
The purpose of this research is to investigate the effects and mechanisms of paeonol (PL), a phenolic compound found in many traditional Chinese formulations, on reversing drug resistance in the ovarian cancer resistant SKOV3/DDP cells. The results showed that PL had significant drug-resistant reversal effect on SKOV3/DDP cells. Flow cytometry showed that PL could inhibit P-glycoprotein (P-gp) function in a concentration-dependent manner. Fluorescent quantitative PCR and cell immunofluorescence techniques were used to detect mechanisms of action. Results revealed that both the inhibitory effect on MDR1/P-gp and metadherin (MTDH) expression and the induction effect on phosphatase and tensin homolog (PTEN), by 15, 30, and 60 μmol·L-1 PL, were increased with increased concentrations of PL (P < 0.01, P < 0.05). The inhibitory effect on MTDH mRNA and the induction effect on PTEN mRNA, by PI3K inhibitor LY294002, were stronger or equivalent to that of the 60 μmol·L-1 PL treated group; however, the inhibition or induction effect on MTDH or PTEN protein were only comparable to the 15 μmol·L-1 PL treated group. The present study shows that the effect of PL on SKOV3/DDP cells may be related to the inhibition of P-gp function and expression, the inhibition of MDR1, MTDH expression, and the induction of PTEN expression, all which can provide a theoretical foundation for PL as a drug resistance reversal agent on the treatment of ovarian cancer chemotherapy resistance.
2.Guizhi Fuling Wan reverses drug resistance by regulating PTEN and MTDH in ovarian cancer SKOV3/DDP Cells
Xiao-Juan GUO ; Li HAN ; Wen-Hua ZANG ; Qian WANG ; Hua BIAN ; Jiu-Lue HU ; Chao-Yun ZHANG
Chinese Journal of Pharmacology and Toxicology 2018;32(4):284-284
OBJECTIVE To detect the reversal effect of Guizhi Fuling Wan on cisplatin-resistant ovarian cancer SKOV3/DDP cells and its relationship with protein expression of phosphatase and tensin homolog (PTEN) and metadherin (MTDH). METHODS Guizhi Fuling Wan (GFW) concentrated solution was prepared according to the Chinese Pharmacopoeia 2015 edition, Wistar rats were given GFW viagavage at 4 g·kg-1·d-1,8 g·kg-1·d-1,16 g·kg-1·d-1,or given saline as blank control for 5 days.Blood samples were taken and the corresponding drug-containing low-dose sera, medium-dose sear, high-dose sera and blank sera were prepared.The XCELLigence RTCA S16 real-time label-free cell analyzer was used to detect the reversal effect by the sera combined with cisplatin or paclitaxel in SKOV3/DDP cells. Annexin V-FITC and PI double-staining were used to detect the apoptosis-inducing effect of the sera in the cells. RT-qPCR and western blot were used to detect the mRNA and protein expression of PTEN and MTDH after the cells treated with the sera. RESULTS The inhibition rate of low-dose sera against SKOV3/DDP cells was less than 5%.After the low-dose sera combined with cisplatin or pacli-taxel, the IC50 of SKOV3/DDP cells against cisplatin and paclitaxel decreased by 3.01 and 1.79-fold, respectively.The total apoptosis rates induced by the low-dose sera,medium-dose sear,high-dose sera and blank sera in SKOV3/DDP cells were 11.08±0.13,19.42±0.30,24.23±0.31,and 3.21±0.24,respec-tively; there was a significant difference between the groups (P<0.01). RT-qPCR results showed that, compared with the blank serum, the sera can up-regulate the expression of PTEN mRNA and down-regulate the expression of MTDH mRNA in a dose-dependent manner. Western blot results showed that the induction effect to PTEN protein and the inhibition effect to MTDH protein by the sera were gradually enhanced with thesera dose increasement. CONCLUSION The resistance reversal effect of Guizhi Fuling Wan on ovarian cancer SKOV3/DDP cells may be related to the inhibition of MTDH, up-regulation of PTEN and induction of apoptosis, providing with an experiment basis for the applica-tion of Guizhi Fuling Wan as a reversal agent for chemotherapy resistance of ovarian cancer.
4.Study on the protective effect and mechanism of Zhilong Huoxue Tongyu Capsule on myocardial ischemia reperfusion injury mice based on serum metabolomics
Mengnan LIU ; Linshen MAO ; Hao WU ; Yuan ZOU ; Qi LAN ; Jinyi XUE ; Ping LIU ; Sijin YANG ; Zhongjing HU
Journal of Beijing University of Traditional Chinese Medicine 2024;47(4):523-531
Objective To observe the protective effect of Zhilong Huoxue Tongyu Capsule(Zhilong Capsule)on myocardial ischemia reperfusion injury(MIRI)in mice,and explore its regulatory mechanism using metabolomics.Methods Using a random number table method,30 C57BL/6J mice were randomly divided into the following three groups:sham operation group,model group,and Zhilong Capsule group(6.24 g/kg),with 10 mice in each group.In mice in the model group and the Zhilong Capsule group,a mouse MIRI model was established by ligating the left anterior descending branch,while mice in the sham operation group underwent threading without ligation.The Zhilong Capsule group began modeling one week after pre-administration and continued to receive intragastric administration for two weeks after modeling once daily.The cardiac function,including the left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS),was assessed by color echocardiography.The myocardial fibrosis and apoptosis were observed by Masson staining and TUNEL staining,respectively.Enzyme-linked immunosorbent assay was used to measure the serum contents of lactate dehydrogenase(LDH)and brain natriuretic peptide(BNP).Liquid chromatography-mass spectrometry combined with multivariate statistical method was performed for serum metabolite detection and identification analysis.Results Compared with the model group,the mice in the Zhilong Capsule group exhibited an increase in LVEF and LVFS,a reduction in cardiac tissue structure disorder,a decrease in myocardial fibrosis,a decrease in cell apoptosis rate,and a decrease in serum LDH and BNP contents(P<0.05).Metabolomics result showed that intervention with Zhilong Capsule significantly regulated 30 differential metabolites related to MIRI.Important metabolic pathways involved 20 pathways related to tyrosine metabolism,arginine and proline metabolism,and vitamin digestion and absorption.Conclusion Zhilong Capsule has a protective effect on MIRI,and it may achieve this effect by regulating pathways related to tyrosine metabolism,arginine and proline metabolism,and vitamin digestion and absorption.
5.Prescriptions and Syndromes of 9 323 Cough Cases in Ancient Chinese Medical Books Based on Rules of Latent Structure Differentiation
Li-ping CHEN ; Jian-sheng LI ; Jing-yu XING ; Jiu-lue HU ; Hua BIAN ; Li-ye PANG
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(18):179-187
Objective:To explore cough cases recorded in ancient traditional Chinese medicine (TCM) books based on the Rules of Latent Structure Differentiation. Method:The 9 323 cough cases in the database of ancient TCM books and pulmonary diseases were extracted. At first, Lantern 5.0 software was used to construct the top 120 TCM hidden structure model with the frequency>100. Then, the obtained hidden variables were comprehensively clustered and interpreted. Result:The 46 hidden variables and 114 hidden classes were obtained through the modeling of 120 traditional Chinese medicines. According to the bayesian information measure (BIC) score, the model score was -161 242.92. The model diagram was formed with Y0, Y5, Y7, Y13, Y35 and Y38 as the cores, and Y36, Y38, Y24, Y19 and Y17 involved 4 hidden classes. Ten comprehensive clustering models were summarized according to the hidden structure flow chart, among which the highest score of Z5 external cold and internal decoction syndrome was 8.4, indicating that the result of syndrome differentiation rules of Z5 had a high degree of support, and the highest mutual information degree and information coverage of Pinellia sinensis were 0.31 and 63%. Z2 had a low score for the syndrome of deficiency of lung qi and Yin, which was -2, and Schisandra had the lowest score of -15, indicating that the syndrome differentiation rules of Z2 was less supportive. Forsythia and Notopterygium both had the highest score of Z6 wind-heat attack lung syndrome and Z10 phlegm and blood-stasis pulmonary syndrome, which was 19.1, indicating that these two TCMs had a great contribution to it. According to the test, the common syndromes of cough were cold and dryness attacking the lung, kidney-Yin deficiency, kidney-Yin deficiency of the lung, cold and internal decoction, wind heat invading the lung, liver fire invading the lung, lung heat burning, phlegm-dampness blocking the lung, phlegm-stasis blocking the lung. The newly discovered cough syndromes were external cold and internal rheum syndrome and phlegm-stasis blocking the lung syndrome. Conclusion:Based on the syndrome differentiation rules of hidden structure, the improved classification of cough syndromes provides ideas for the demonstration of tacit knowledge of TCM and methodological reference for the improvement of syndromes of other diseases, and is conducive to the development of valuable new prescriptions.
6. Basal metabolic rate, body fat distribution and its correlation among Xibo adults in Xinjiang
Guo-Chang XU ; Yan-Li HOU ; Rong-Zhi LIU ; Neng-Neng HU ; You-Feng WEN
Acta Anatomica Sinica 2020;51(2):289-293
Objective To understand the distribution characteristics of body fat content and basal metabolic rate among Xibo adults in Xinjiang and to explore the correlation between them. Methods The people aged between 35 and 70 were randomly selected to be the research object, and a total of 536 people (263 males and 273 females) were selected for the study. Subcutaneous fat, visceral fat, weight, stature, defat weight, body fat rate and basal metabolic rate were measured using the body composition analyzer. The correlation between body fat content and basal metabolic rate was studied by regression analysis, and regression equation coefficient was calculated. Results There were statistically significant in total fat, defate body weight and body fat percentage (P<0. 05) of different aged Xibo adults in Xinjiang, except for male visceral fat and female subcutaneous fat. There were statistically significant subcutaneous fat, total fat and body fat percentage(P<0. 05) between the sexes, except for visceral fat. The visceral fat content among Xibo adults in Xinjiang was negatively correlated with basal metabolic rate (P<0. 05). Conclusion Body lipid distribution is differences in different aged and gender among Xibo adults in Xinjiang. There is a negative correlation between visceral fat and basal metabolic rate.
7.Characteristics of Basal Sex Hormone Levels and Anti-müllerian Hormone Levels in 1221 Women of Different Ages:A Retrospective Study on the Law of Women Reproductive Aging in the "Seven-year Period" Theory
Wanshi LIANG ; Yiru LIAO ; Jinghan FU ; Luodan HU ; Hongyan YANG ; Jian LIU ; Fangping CHENG ; Guangning NIE
Journal of Traditional Chinese Medicine 2024;65(13):1369-1374
ObjectiveTo explore the law of women reproductive aging based on theory of "seven-year period" in traditional Chinese medicine(TCM) through analyzing the characteristics of basic sex hormone levels and anti-müllerian hormone levels in women of different ages. MethodsThe data of female who visited Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2018 to December 2022 and accepted basic hormone and anti-müllerian hormone determination were collected retrospectively. According to the age of subjects, they were divided into the "1
8.A prospective study on application of human umbilical cord mesenchymal stem cells combined with autologous Meek microskin transplantation in patients with extensive burns.
Tian Tian YAN ; Rong XIAO ; Ying WANG ; Guo An LIN ; Yin ZHENG ; Hui ZHAO ; Wen Jun LI ; Xin Zhi SHANG ; Jin Song MENG ; Dong Sheng HU ; Song LI ; Chao WANG ; Zhi Chen LIN ; Hong Chang CHEN ; Dong Yan ZHAO ; Di TANG
Chinese Journal of Burns 2023;39(2):114-121
Objective: To investigate the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with autologous Meek microskin transplantation on patients with extensive burns. Methods: The prospective self-controlled study was conducted. From May 2019 to June 2022, 16 patients with extensive burns admitted to the 990th Hospital of PLA Joint Logistics Support Force met the inclusion criteria, while 3 patients were excluded according to the exclusion criteria, and 13 patients were finally selected, including 10 males and 3 females, aged 24-61 (42±13) years. A total of 20 trial areas (40 wounds, with area of 10 cm×10 cm in each wound) were selected. Two adjacent wounds in each trial area were divided into hUCMSC+gel group applied with hyaluronic acid gel containing hUCMSCs and gel only group applied with hyaluronic acid gel only according to the random number table, with 20 wounds in each group. Afterwards the wounds in two groups were transplanted with autologous Meek microskin grafts with an extension ratio of 1∶6. In 2, 3, and 4 weeks post operation, the wound healing was observed, the wound healing rate was calculated, and the wound healing time was recorded. The specimen of wound secretion was collected for microorganism culture if there was purulent secretion on the wound post operation. In 3, 6, and 12 months post operation, the scar hyperplasia in wound was assessed using the Vancouver scar scale (VSS). In 3 months post operation, the wound tissue was collected for hematoxylin-eosin (HE) staining to observe the morphological changes and for immunohistochemical staining to observe the positive expressions of Ki67 and vimentin and to count the number of positive cells. Data were statistically analyzed with paired samples t test and Bonferronni correction. Results: In 2, 3, and 4 weeks post operation, the wound healing rates in hUCMSC+gel group were (80±11)%, (84±12)%, and (92±9)%, respectively, which were significantly higher than (67±18)%, (74±21)%, and (84±16)% in gel only group (with t values of 4.01, 3.52, and 3.66, respectively, P<0.05). The wound healing time in hUCMSC+gel group was (31±11) d, which was significantly shorter than (36±13) d in gel only group (t=-3.68, P<0.05). The microbiological culture of the postoperative wound secretion specimens from the adjacent wounds in 2 groups was identical, with negative results in 4 trial areas and positive results in 16 trial areas. In 3, 6, and 12 months post operation, the VSS scores of wounds in gel only group were 7.8±1.9, 6.7±2.1, and 5.4±1.6, which were significantly higher than 6.8±1.8, 5.6±1.6, and 4.0±1.4 in hUCMSC+gel group, respectively (with t values of -4.79, -4.37, and -5.47, respectively, P<0.05). In 3 months post operation, HE staining showed an increase in epidermal layer thickness and epidermal crest in wound in hUCMSC+gel group compared with those in gel only group, and immunohistochemical staining showed a significant increase in the number of Ki67 positive cells in wound in hUCMSC+gel group compared with those in gel only group (t=4.39, P<0.05), with no statistically significant difference in the number of vimentin positive cells in wound between the 2 groups (P>0.05). Conclusions: The application of hyaluronic acid gel containing hUCMSCs to the wound is simple to perform and is therefore a preferable route. Topical application of hUCMSCs can promote healing of the autologous Meek microskin grafted area in patients with extensive burns, shorten wound healing time, and alleviate scar hyperplasia. The above effects may be related to the increased epidermal thickness and epidermal crest, and active cell proliferation.
Female
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Humans
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Male
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Burns/surgery*
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Cicatrix
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Eosine Yellowish-(YS)
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Hyaluronic Acid/therapeutic use*
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Hyperplasia
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Ki-67 Antigen
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Prospective Studies
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Umbilical Cord
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Vimentin
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Young Adult
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Adult
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Middle Aged