1.Research Progress on Antitumor Effect of AMPK/mTOR Signaling Pathway Regulated by Traditional Chinese Medicine
Xiafei ZHENG ; Dongdong LI ; Peimin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):268-276
With the increasing incidence and mortality of malignant tumors year by year, the prevention and treatment of malignant tumors has become a hot field of research. Although the existing anti-tumor treatment methods such as surgery, radiotherapy, chemotherapy, immunity and targeting have achieved some results, there are also obvious shortcomings, which are not conducive to the improvement of patients' quality of life and long-term treatment. Therefore, seeking a new efficient and safe treatment has become a hot topic of concern for many oncologists. adenosine monophosphate activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) signaling pathway can participate in intracellular energy metabolism and affect the pathogenesis and outcome of tumors through multiple mechanisms. It is widely mentioned in the occurrence and development of many tumors. The activity level of this pathway is closely related to the abnormal proliferation and invasion of tumor cells, and is considered as an important pathway for anti-tumor therapy research. The anti-tumor treatment of traditional Chinese medicine(TCM) has significant advantages such as syndrome differentiation and treatment and sample consideration. The study found that flavonoids, alkaloids, polyphenols, saponins and other active components of traditional Chinese medicine, as well as the traditional Chinese medicine compound Xiangbei San, Yiqi Fuzheng Jiedu decoction, Yiqi Fuzheng prescription, etc can activate the AMPK/ mTOR signaling pathway by regulating the expression of AMPK/mTOR signaling pathway and upstream and downstream proteins, thereby inducing tumor cell autophagy and apoptosis, inhibiting tumor angiogenesis and epithelial mesenchymal transformation, regulating aerobic glycolysis and energy metabolism, and reversing drug resistance to exert anti-tumor effects. In this paper, by summarizing the research achievements of TCM anti-tumor in recent years, the specific mechanism of action of TCM regulating AMPK/ mTOR signaling pathway against tumor was discussed, aiming to provide ideas and references for the research and development of anti-tumor new drugs.
2.Preparation of heparinized acellular vascular scaffold and hemocompatibility evaluation
Xiafei LI ; Lingling ZHAO ; Feng LIANG ; Xuewei ZHANG ; Jinjin ZHANG ; Fei LIN ; Tuo YANG ; Liang ZHAO
Chinese Journal of Tissue Engineering Research 2024;28(17):2631-2636
BACKGROUND:Acellular vascular scaffolds can mimic the microstructure and function of native blood vessels,but some extracellular matrix loss occurs during their preparation,which affects their hemocompatibility.Therefore,it is necessary to modify them to improve their hemocompatibility. OBJECTIVE:To assess the hemocompatibility of acellular vascular scaffold prepared by Triton-x100/heparin sodium treatment. METHODS:The abdominal aorta was taken from SD rats and randomly divided into control and experimental groups.The control group was treated with Triton-x100 for 48 hours.The experimental group was treated with Triton-x100 for 48 hours and then treated with heparin sodium.The morphology and hydrophilicity of the two groups of acellular vascular scaffolds were detected.The hemocompatibility of the two groups of acellular vascular scaffold was evaluated by recalcification coagulation time test,platelet adhesion test,dynamic coagulation time test,hemolysis test,and complement activation test. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the surface of the two groups of vascular scaffolds was relatively intact,and a large number of fiber filaments appeared on the surface of the scaffolds after decellularity treatment,and the surface microstructure changed significantly.The water contact angle of the two groups of vascular scaffolds was smaller than that of natural vessels(P<0.000 1).There was no significant difference in water contact angle between the two groups(P>0.05).(2)The coagulation time of vascular scaffold was longer in the experimental group than in the control group(P<0.05).The number of platelets attached to the scaffold membrane was less in the experimental group than that in the control group(P<0.000 1).The coagulation index was greater in the experimental group than that in the control group(P<0.01),and the complement level was lower in the experimental group than that in the control group(P<0.001).The hemolysis rate of the two groups was lower than 5%of the national standard.(3)To conclude,acellular scaffold treated with Triton-x100/heparin sodium has excellent hemocompatibility.
3.Promotion effect of FOXCUT as a microRNA sponge for miR-24-3p on progression in triple-negative breast cancer through the p38 MAPK signaling pathway
Xiafei YU ; Fangze QIAN ; Xiaoqiang ZHANG ; Yanhui ZHU ; Gao HE ; Junzhe YANG ; Xian WU ; Yi ZHOU ; Li SHEN ; Xiaoyue SHI ; Hongfei ZHANG ; Xiao’an LIU
Chinese Medical Journal 2024;137(1):105-114
Background::Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with a poor prognosis. According to new research, long noncoding RNAs (lncRNAs) play a significant role in the progression of cancer. Although the role of lncRNAs in breast cancer has been well reported, few studies have focused on TNBC. This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript (FOXCUT) in triple-negative breast cancer.Methods::Based on a bioinformatic analysis of the cancer genome atlas (TCGA) database, we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues, which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University. The functions of FOXCUT in proliferation, migration, and invasion were detected in vitro or in vivo. Luciferase assays and RNA immunoprecipitation (RIP) were performed to reveal that FOXCUT acted as a competitive endogenous RNA (ceRNA) for the microRNA miR-24-3p and consequently inhibited the degradation of p38. Results::lncRNA FOXCUT was markedly highly expressed in breast cancer, which was associated with poor prognosis in some cases. Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo. Mechanistically, FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38, which might act as an oncogene in breast cancer. Conclusion::Collectively, this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.
4.Genetic stability analysis of two recombinant rotaviruses harboring foreign gene insertions within the NSP3 region
Shan LI ; Xiafei LIU ; Junjie YU ; Dandi LI ; Zhaojun DUAN
Chinese Journal of Experimental and Clinical Virology 2024;38(1):1-6
Objective:To analyze the genetic stability of two recombinant rotaviruses (rLLR/NSP3 NLuc) and (rLLR/NSP3 CoV2/RBD) that are inserted and express exogenous genes for continuous passage and proliferation on MA104 cells.Methods:After measuring the titers of two recombinant rotavirus strains, they were transferred to the P2 generation according to MOI0.01. Subsequently, the previous generation of virus lysate was diluted and activated at 1∶100, and MA104 cells were continuously infected for 18 generations (P20). The virus titers of the P1, P5, P10, P15, and P20 generation of cell lysate were measured using indirect immunofluorescence, and RT-PCR identification and dsRNA PAGE silver staining were performed. The luciferase activity of rLLR/NSP3-NLUc was also detected.Results:No inserted fragment loss was found in the recombinant rotavirus rLLR/NSP3 NLuc within 20 generations, with recombinant virus titers ranging from 3.85~5.16 × 10 6 FFU/ml, with strong luciferase signals in each generation. The recombinant rotavirus rLLR/NSP3 CoV2/RBD showed loss of inserted fragments in the 6th generation, with infectivity titers ranging from 2.6 to 3.36 in the first 5 generations of the recombinant virus × 10 6 FFU/ml. Conclusions:The recombinant rotavirus with 582 bp NLuc inserted at the end of the NSP3 gene has good genetic stability, while the recombinant rotavirus with 885 bp RBD inserted at the end of the NSP3 gene was only stable in the first 5 generations, indicating that foreign genes can be inserted at the end of the NSP3 gene of the recombinant rotavirus, and the insert can express, but its stability requires more in-depth research.
5.Construction of quality indicator system for pelvic floor rehabilitation in patients after cervical cancer surgery based on the three-dimensional quality structure model
Yongxia LI ; Hongmei LU ; Xiafei LI ; Huanhuan CUI ; Yuanli DENG
Chinese Journal of Practical Nursing 2024;40(26):2021-2027
Objective:To construct quality indicator system for pelvic floor rehabilitation in patients after cervical cancer surgery based on the three-dimensional quality structure model, and provide a basis for evaluating the quality of pelvic floor rehabilitation.Methods:Based on the "structure-process-result" three-dimensional quality structure model, a quality indicator system for pelvic floor rehabilitation management in patients after cervical cancer surgery was constructed by literature review, semi-structured interview and Delphi technique from January to May 2023, and the importance and weight of the indicators was identified.Results:A total of 15 experts were included, including 3 males and 12 females, aged 38-56 (46.79 ± 6.38) years. The effective questionnaire recovery rates of 2 rounds of expert correspondence were 15/15, the authority coefficients of the experts were 0.938 and 0.923, and the Kendall coordination coefficients were 0.139 - 0.337 and 0.107 - 0.152 (all P<0.01). The final quality indicator system for pelvic floor rehabilitation in patients after cervical cancer surgery included 3 primary indicators, 10 secondary indicators and 42 tertiary indicators. Conclusions:The quality indicator system for pelvic floor rehabilitation in patients after cervical cancer surgery constructed based on three-dimensional quality structure model was scientific and practical, which could be used as an indicator for evaluating the quality of pelvic floor rehabilitation in patients after cervical cancer surgery.
6.Summary of the best evidence for perioperative nutrition management in patients with pancreatic cancer
Li YUAN ; Hailing ZHANG ; Xiaofei QIAO ; Xiafei CHU
Chinese Journal of Modern Nursing 2024;30(3):351-357
Objective:To search the best evidence for perioperative nutrition management in pancreatic cancer patients, so as to provide evidence basis for optimization of perioperative nutrition management in pancreatic cancer patients.Methods:Evidence on perioperative nutrition management for pancreatic cancer patients was systematically searched in Cochrane Library, British Medical Journal (BMJ) Best Practice, UpToDate, National Institute for Health and Clinical Excellence, PubMed, China National Knowledge Infrastructure, WanFang Data, VIP, Chinese Medical Association Network and other domestic and foreign databases and nutrition related websites. The search types included clinical decision-making, guidelines, expert consensus, evidence summary, and systematic review. The search period was from database establishment to February 10, 2023.Results:A total of 17 articles were included, including 8 guidelines, 6 expert consensus, and 3 systematic reviews. A total of 26 pieces of evidence were summarized from 6 aspects, including management general principles, energy and protein requirements, nutritional risk screening and assessment, nutritional support, complication management, and post discharge management.Conclusions:The process of extracting the best evidence of perioperative nutrition management for pancreatic cancer patients is scientific and rigorous. Medical and nursing staff can improve the quality of nutrition management for patients with pancreatic cancer and promote the recovery of patients according to the actual clinical situation.
7.Advances of human oral viral vaccine development.
Shan LI ; Xiafei LIU ; Zhaojun DUAN
Chinese Journal of Biotechnology 2023;39(9):3556-3565
Development of a vaccine that can simultaneously induce effective mucosal immunity and systemic immunity is an ideal goal to prevent mucosal pathogenic infections. The digestive tract has many sites for inducing mucosal immunity, including the mouth, stomach and small intestine. An ideal oral viral vaccine can not only induce better local and distal mucosal immunity, but also produce better systemic immunity. The oral viral vaccine has also attracted much attention because of its painless vaccination, self-administration and other advantages. Due to the complexity of human digestive tract environment and mucosal immunity, only three oral attenuated live vaccines have been successfully marketed for human use. This review summarizes the characteristics of gastrointestinal mucosal immunity, the current types and research status of oral viral vaccines, and the challenges faced by oral viral vaccines, with the hope to facilitate the research and development of oral viral vaccines for human use in China.
Humans
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Viral Vaccines
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Vaccination
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Immunity, Mucosal
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Vaccines, Attenuated
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Vaccine Development
8.Risk factors and their predictive value for intensive care unit acquired weakness in patients with sepsis
Minghang LI ; Huanzhang SHAO ; Cunzhen WANG ; Chao CHEN ; Ling YE ; Mingyue DING ; Shengyong REN ; Xiafei ZHAO ; Xingwei WANG ; Bingyu QIN
Chinese Critical Care Medicine 2021;33(6):648-653
Objective:To explore the risk factors of intensive care unit acquired weakness (ICUAW) in patients with sepsis, and to evaluate the predictive value of each risk factor for ICUAW.Methods:A case control study was conducted, 60 septic patients admitted to the intensive care unit (ICU) of Henan Provincial People's Hospital from October 20, 2020 to February 20, 2021 were enrolled. The patients were divided into two groups: sepsis ICUAW group and sepsis non-ICUAW group. The data of gender, age, body mass index (BMI), acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, complications, mechanical ventilation, duration of ICUAW, length of stay in ICU, fasting blood glucose, blood lactic acid (Lac), procalcitonin (PCT), C-reactive protein (CRP), sequential organ failure assessment (SOFA) score, outcome, antimicrobial agent, glucocorticoid, sedatives and analgesics drugs and vasoactive drugs were collected. Risk factors were screened by univariate Logistic regression analysis, and odds ratio ( OR) was adjusted by multivariate binary logistic regression, P < 0.05 was considered as independent risk factors. Finally, the receiver operating characteristic curve (ROC curve) was drawn to analyze the predictive value of independent risk factors. Results:The APACHEⅡ score of the sepsis ICUAW group was significantly higher than that of the sepsis non-ICUAW group (23.05±8.17 vs. 15.33±4.89, P < 0.05), the total length of stay in the ICU was significantly longer than that of the sepsis non-ICUAW group (days: 15.1±9.2 vs. 8.5±3.4, P < 0.05), the improvement rate of patients was significantly lower than that of the sepsis non-ICUAW group [45.0% (9/20) vs. 95.0% (38/40), P < 0.05]. After univariate Logistic regression and multicollinearity test analysis, 7 factors including APACHEⅡ score, average SOFA score, blood lactic acid, proportion of mechanical ventilation, sedatives and analgesics drugs, type of antibiotics and type of vasoactive drugs were included in the binary Logistic regression model [ OR: 1.21, 2.05, 2.26, 0.21, 1.54, 2.07, 1.38, 95% confidence interval (95% CI): 1.09-1.35, 1.42-2.94, 1.12-4.57, 0.05-0.66, 1.03-2.29, 1.27-3.37, 0.96-2.00, all P < 0.05]. Hosmer-Lemchaw test P = 0.901, and the correct percentage of prediction was 85%, indicating good model fit. Multivariate binary Logistic regression analysis showed that APACHEⅡ score and average SOFA score were independent risk factors for the occurrence of ICUAW in septic patients (APACHEⅡscore: OR = 1.17, 95% CI was 1.004-1.376, P = 0.044; average SOFA score: OR = 1.86, 95% CI was 1.157-2.981, P = 0.01). ROC curve analysis showed that the mean value of APACHEⅡ score, average SOFA score and their combined detection had a certain predictive value for the occurrence of ICUAW in sepsis patients, areas under ROC curve (AUC) were 0.787, 0.881, 0.905, 95% CI was 0.646-0.928, 0.791-0.972, 0.828-0.982, all P < 0.05. When the cut-off value was 19.500, 6.225, 0.375, the sensitivity was 75%, 90%, 90%, and the specificity were 80%, 80%, 85%, respectively. Conclusion:APACHEⅡ score and average SOFA score can be used as independent risk factors for the occurrence of ICUAW in sepsis, and their combined predictive value is better than that of individual index.
9.Protective effect of transient receptor potential melastatin 2 inhibitor A10 on oxygen glucose deprivation/reperfusion model.
Jianguo NIU ; Xingyu LIU ; Minghua HUANG ; Xiafei YU ; Fangfang LI ; Wei YANG ; Kang MA ; Zhuoqun HUANG
Journal of Zhejiang University. Medical sciences 2021;50(1):106-112
To investigate the effect of transient receptor potential melastatin 2 (TRPM2) inhibitor A10 on oxygen glucose deprivation/reperfusion (OGD/R) injury in SH-SY5Y cells.:Human neuroblastoma SH-SY5Y cells were subject to OGD/R injury,and then were divided into blank control group,model control group and A10 group randomly. The cell survival rate was detected by cell counting kit 8 (CCK-8); the level of cellular reactive oxygen species (ROS) was detected by reactive oxygen detection kit; the mitochondrial membrane potential was detected by tetramethylrhodamine (TMRM) method; the number of apoptotic cells was detected by TUNEL apoptosis assay kit; the protein expression level of cleaved caspase 3 was detected by Western blot.:Compared with 3,20,30,50, has lower cytotoxicity and better inhibition effect on channel activity. Compared with the model control group,ROS level was reduced,the mitochondrial membrane potential was improved,the number of apoptosis cells was reduced ,and the expression of cleaved caspase 3 was significantly reduced in the A10 group(all <0.05). : A10 can alleviate cell damage after OGD/R by inhibiting TRPM2 channel function,reducing extracellular calcium influx,reducing cell ROS levels,stabilizing mitochondrial membrane potential levels,and reducing apoptosis.
Apoptosis
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Benzeneacetamides
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Cell Survival
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Glucose
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Humans
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Oxygen/metabolism*
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Piperidones
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Reactive Oxygen Species/metabolism*
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Reperfusion
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TRPM Cation Channels
10.Research progress in metronomic photodynamic therapy
Xiafei SHI ; Yingxin LI ; Wendong JIN ; Huijuan YIN
International Journal of Biomedical Engineering 2019;42(3):268-275
Metronomic photodynamic therapy (mPDT) is a new type of photodynamic therapy (PDT) that has received much attention in recent years. It has a similar therapeutic mechanism to traditional PDT, i.e. the photosensitizer is irradiated by visible light irradiation with a specific wavelength, and tissue oxygen photochemical reactions produce cytotoxic reactive oxygen species (ROS) that selectively kill rapidly proliferating tumor cells. Unlike traditional PDT, the photosensitizer and light in mPDT are continuously transmitted at a low time and at a low rate, and the specificity of tumor treatment is enhanced by apoptosis. In this paper, the current researches on the in vitro and in vivo effects and mechanisms of mPDT, as well as the research status of photosensitizers and light sources for in vivo research, were reviewed, with a view to understanding the existing mPDT technology and providing reference for the further studies. This review paper can provide a basic for promoting the clinical research and application of mPDT.

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