1.Advance in resistance mechanism of cancer stem cells therapy
Mengxue CAO ; Fan SUN ; Houwen LIN
Journal of Pharmaceutical Practice 2017;35(3):193-196,247
Lung cancer is the leading cause of cancer deaths worldwide.Recurrence and metastasis are the primary reasons for its poor prognosis.Growing evidence has proposed that lung cancer may be driven by cancer stem cells (CSCs), which may be responsible for the poor outcome of lung cancer.The resistance mechanisms of cancer stem cells include four aspects: high expression of the chemo-resistant efflux transporter ABC in CSCs populations, over-expression of ALDH, efficient DNA damage repair system, developmental pathway activation.The tolerance mechanism of CSCs was described to provide theoretical basis for clinical treatment and development of new anti-tumor drugs.
2.Effect of knockdown of PRDX6 on adaptive expression of bile acid transporter in HepG2 cells induced by rifampicin
Liufang QU ; Mengxue HUANG ; Shiguo CAO ; Gang CHEN ; Jianming XU ; Weiping ZHANG
Acta Universitatis Medicinalis Anhui 2024;59(4):660-665
Objective To investigate the role of knockdown of peroxiredoxin-6(PRDX6)in injury and adaptive expression of bile acid transporter in human hepatoellular carcinomas(HepG2)cells induced by rifampicin(RFP).Methods Cells in logarithmic growth phase were uniformly inoculated in six-well plates,and HepG2 cells were transiently transfected with specific PRDX6-siRNA and control-siRNA to construct the knockdown group and control group.After 24 h of induction with 100 μmol/L RFP,Western blot and qRT-PCR were performed to detect the protein and gene expression levels of PRDX6,multidrug resistance protein 1(MDR1),multidrug resist-ance-associated proteins 2,3 and 4(MRP2,MRP3 and MRP4),and Na+/taurine taurocholate cotransporter pro-tein(NTCP).Annexin V-FITC/PI double staining assay was used to detect the apoptosis rate of cells in each group;CCK-8 assay was used to detect the changes of cell proliferation in each group;The relative contents of ala-nine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),indirect bilirubin(IBIL)and total bile acid(TBA)in the supernatant of cell culture medium of each group were detected by kits.Results RFP increased the protein and gene expression levels of MRP2,MRP3,MRP4,MDR1,NTCP and PRDX6 in HepG2 cells(P<0.05),while the protein and gene expression levels of MRP2,MRP3,MRP4,MDR1 and NTCP decreased to different degrees after PRDX6 knockdown(P<0.05).In addition,PRDX6 knockdown re-sulted in increased apoptosis rate of HepG2 cells(P<0.05),decreased cell proliferation ability(P<0.05),and increased levels of cell injury markers(ALT,AST,TBIL,DBIL,TBA)in cell culture supernatants(P<0.05).Conclusion RFP increased the protein and gene expression of bile acid transporter and PRDX6 to increase in HepG2 cells.However,following knockdown of PRDX6 and treatment with RFP,the protein and gene expression levels of the bile acid transporter decreased and cell injury was aggravated,suggesting that PRDX6 played a protec-tive role in RFP-induced adaptive response in HepG2 cells.
3.Summary of the best evidence for fatigue management in children with tumors
Jinjin CAO ; Yuanyuan WANG ; Qian DAI ; Meng LI ; Mengxue HE ; Nanping SHEN ; Yahui ZUO ; Mei LI
Chinese Journal of Modern Nursing 2024;30(27):3685-3693
Objective:To evaluate and summarize the best evidence on fatigue management in children with tumors both domestically and internationally, providing reference for medical and nursing staff to improve fatigue symptoms in children.Methods:The evidence on fatigue management in children with tumors, including best practices, recommended practices, guidelines, systematic reviews, evidence summaries, and expert consensus, was systematically retrieved from clinical decision support systems, guideline websites, professional association websites, and databases both domestically and internationally. The search period was from database establishment to April 2023. Two researchers independently conducted literature quality evaluation and evidence extraction.Results:A total of 17 articles were included, including four guidelines and 13 systematic reviews. Thirty-two best pieces of evidence were extracted from six aspects of assessment and screening, identification of risk factors, health education, exercise intervention, medication intervention, and other interventions of fatigue in children with tumors.Conclusions:The best evidence for fatigue management in children with tumors is summarized, which can provide a basis for medical and nursing staff to improve their fatigue symptoms. It is recommended that medical and nursing staff combine clinical context, professional opinions, and patient wishes to screen the best evidence and develop personalized fatigue management programs.
4.Preliminary practice of multidisciplinary cooperative vaccination management model for pediatric patients with hematological and oncological diseases
Haishan RUAN ; Yijin GAO ; Yi FEI ; Qing CAO ; Wenjuan CHEN ; Jia CHEN ; Hua ZHANG ; Xingwei WANG ; Mengxue HE ; Fen ZHOU
Chinese Journal of Pediatrics 2021;59(4):305-310
Objective:To preliminarily establish the multidisciplinary cooperative vaccination management model for pediatric patients with hematological and oncological diseases, and to explore its feasibility.Methods:In this prospective study a total of 150 children with hematological and oncological diseases visited immunization clinic of Shanghai Children′s Medical Center from March 2017 to August 2018 were enrolled in this study. After establishing the multidisciplinary team, designing vaccination plan, staff training, implementation and quality control, a multidisciplinary immunization clinic was set up and the vaccination plan were implemented. The implementation rate of vaccination immunization, the HBsAb level and serum hepatitis B surface antibody (HBsAb) level before and after treatment, the HBsAb level and serum immunoglobulin G antibody (IgG) levels of measles, mumps, rubella (MMR) before and 6 months after immunization, the vaccine-related adverse reactions were assessed prospectively. Chi-square test or Fisher exact test was used to compare the differences of antibody level.Results:A total of 124 cases had been vaccinated as planned, with a coverage rate of 82.7%. Among these cases, the difference of HBsAb positive rate before and after treatment was significant (62.9% (78/124) vs.13.7% (17/124), χ2= 63.489, P<0.01). In 64 cases that completed three doses of hepatitis B immunization, there was a significant difference in HBsAb positive rate before and 6 months after immunization (6.3% (4/64) vs. 98.4% (63/64), P<0.01). In 40 cases that completed MMR immunization, the IgG antibody positive rate for measles (22.5% (9/40) vs. 82.5% (33/40), χ2 =31.746, P<0.01), mumps (22.5% (9/40) vs.82.5% (33/40), χ2 =28.872, P<0.01), rubella (25.0% (10/40) vs.62.5% (25/40), χ2 =11.429, P<0.01) before and 6 months after immunization were significantly different. Of the 421 doses of immunization, 25 (5.9%) doses reported controlled systemic or local adverse event. Conclusions:The immunization of pediatric patients with hematological and oncological diseases is of great importance. The newly-developed multidisciplinary cooperation immunization model for Chinese children with hematological and oncological diseases is feasible, and the immunization protocol is safe and has a certain effect.
5.Effects of knockdown of MANF on adaptive expression of bile acid transporter in HepG2 cells induced by rifampicin
Shiguo Cao ; Qiong Dai ; Mengxue Huang ; Liufang Qu ; Jianming Xu ; Weiping Zhang
Acta Universitatis Medicinalis Anhui 2023;58(4):665-671
Objective :
To investigate the effect of mesencephalic astrocyte-derived neurotrophic factor (MANF) on the adaptive expression of bile acid transporter in human hepatoellular carcinomas (HepG2) induced by rifampicin (RFP) .
Methods:
The control group cell line (Y07) and the knockdown group cell line (Y25) were constructed by lentiviral stable transfection technology.The Y07 and Y25 cells were treated with RFP of 200 μmol / L for 48 h, and qRT-PCR and Western blot were used to detect the protein and gene expression levels of MANF,bile salt export pump ( BSEP) ,multidrug resistance-related proteins 2 /3 /4 ( MRP2 ,MRP3 ,MRP4) ,multidrug resistance protein 1 (MDR1) ,organic solute transporter a / β ( OSTα/ β) ,organic anion transporter ( OATP2B1) .The protein and gene expression levels of proliferating cell nuclear antigen ( PCNA) ,proliferating cell marker Ki67 were used to evaluate the proliferation of cells in each group changes in levels.Changes in the protein and gene expression levels of C / EBP homologous protein( CHOP) and cysteinyl aspartate specific proteinase-3 ( Caspase-3) were used to evaluate the apoptosis of cells in each group.The relative contents of alanine aminotransferase(ALT) ,aspartate aminotransferase(AST) ,alkaline phosphatase ( ALP) ,total bilirubin ( TBIL) ,indirect bilirubin ( IBIL) and total bile acid(TBA) in the supernatant of cell culture medium of each group were detected by kits.
Results:
RFP could induce the protein and gene expression of MANF,BSEP ,MRP2 ,MRP3 ,MRP4 ,MDR1 ,OSTα , OSTβ , OATP2B1 in HepG2 cells (P <0. 05 ) ,while the protein and gene expression levels of BSEP ,MRP2 ,MRP3, MRP4,MDR1,OSTα、OSTβ、OATP2B1 decreased after MANF knockdown(P<0. 05) .Moreover,under the action of RFP,the protein expression of PCNA and Ki67 in the knockdown group was still higher.The protein and gene levels of CHOP and Caspase-3 significantly increased after MANF knockdown(P<0. 05) .The levels of the hepatic cell injury markers in the cell supernatant increased significantly(P<0. 05) .
Conclusion
RFP can induce the expression of bile acid transporter such as BSEP,MRP2,MRP3,MRP4,MDR1,OSTα , OSTβ and OATP2B1 to increase in HepG2 cells(P<0. 05) ,but the expression of bile acid transporter of HepG2 after MANF knockdown will significantly decrease under the induction of rifampicin(P<0. 05) ,and cell indury is aggravated,indicating that MANF plays a protective role in RFP-induced adaptive responses by regulating the bile acid transporter.
6.Study of intestinal bacterial overgrowth in patients with chronic liver disease
Mengxue Huang ; Gang Chen ; Peng Wang ; Shiguo Cao ; Jianming Xu ; Qiao Mei ; Rutao Hong ; Weiping Zhang
Acta Universitatis Medicinalis Anhui 2022;57(7):1134-1137
Objective:
To detect the difference in the incidence of small intestinal bacterial overgrowth(SIBO) in patients with liver cirrhosis and chronic hepatitis fibrosis(CHF) with the lactulose hydrogen breath test(LHBT), and to explore the relationship between SIBO and inflammatory factors and oxidative stress related indicators.
Methods:
LHBT was performed on 38 CHF patients, 60 cirrhosis patients and 31 healthy controls to evaluate the incidence of SIBO. The patients were further divided into SIBO-positive and negative group. Then we compared related clinical symptoms and laboratory tests between the two groups and detected lipopolysaccharide(LPS), interleukin(IL)-6, tumor necrosis factor(TNF)-α, IL-10 level, and several kinds of oxidative stress indicators such as diamine oxidase(DAO), superoxide dismutase(SOD), glutathione(GSH), catalase(CAT). Statistical analysis was conducted to analyze the correlation between the concentration of LPS, IL-6, TNF-α, DAO, SOD, GSH, CAT and LHBT summation value.
Results:
(1) The positive rate of SIBO in CHF group, cirrhosis group and control group was 36.84%, 60.00% and 9.68%, respectively. The difference was statistically significant(P<0.01).(2) The differences in CTP classification and ascites were statistically significant between the two subgroups with and without SIBO(P<0.05).(3) The levels of LPS, IL-6, CAT, DAO and SOD in SIBO-positive group were higher than those in negative group(P<0.05). However, the concentrations of IL-10, TNF-α and GSH were similar between the two groups.(4) The LHBT summation value was positively correlated with the concentrations of LPS, IL-6, DAO, SOD and CAT in serum(P<0.05), but had no significant correlation with TNF-α, IL-10 and GSH.
Conclusion
Compared with healthy controls, CHF and cirrhosis patients are more likely to develop SIBO. It is also related to the increase of inflammatory factors and oxidative stress indexes in peripheral blood. SIBO may aggravate the inflammatory response of CHF and cirrhosis patients through intestinal flora dysregulation and oxidative stress, thus aggravating the disease change.