1.Effects of pulsed radiofrequency application to dorsal root ganglia on expression of IRF8 in spinal cord and BDNF in nucleus accumbens of rats with neuropathic pain
Rongguo LIU ; Xingwu LIN ; Xiangyu FANG ; Xueru XU
Chinese Journal of Anesthesiology 2017;37(5):540-543
Objective To evaluate the effects of pulsed radiofrequency (PRF) application to dorsal root ganglia on the expression of interferon regulatory factor 8 (IRF8) in the spinal cord and brain-derived neurotrophic factor (BDNF) protein in the nucleus accumbens of rats with neuropathic pain (NP).Methods Forty healthy pathogen-free male Wistar rats,weighing 180-200 g,aged 2 months,were divided into 4 groups (n=10 each) using a random number table:sham operation group (group Sham),group NP,sham PRF group (group SPRF) and PRF group.NP was induced by chronic constriction injury (CCI) to the left sciatic nerve of anesthetized rats.The mechanical paw withdrawal threshold (MWT) was measured before CCI and at 3,7,10,14,21,28,35 and 42 days after CCI.Sucrose preference test and forced-swim test were performed at 42 days after CCI for determination of the expression of IRF8 in the spinal cord and BDNF in the nucleus accumbens by Western blot.Results Compared with group Sham,the MWT at each time point after CCI and rate of preference for sucrose were significantly decreased,the duration of immobility in forced-swim test was prolonged,and the expression of IRF8 and BDNF was up-regulated in NP,SPRF and PRF groups (P<0.05).Compared with group NP,the MWT at 10-42 days after CCI and rate of preference for sucrose were significantly increased,the duration of immobility in forced-swim test was shortened,and the expression of IRF8 and BDNF was down-regulated in group PRF (P<0.05),and no significant changes were found in the parameters mentioned above in group SPRF (P>O.05).Conclusion The mechanism by which PRF application to dorsal root ganglia alleviates NP and depressive-like behaviors is probably related to down-regulation of the expression of IRF8 in the spinal cord and BDNF in the nucleus accumbens of rats.
2.Comparative study of laparoscopic gastrectomy D2 radical surgery and open gastrectomy for upper stomach cancer
Wenlin LIN ; Zhixiong LI ; Yanchang XU ; Xueru XIE ; Zhiqing HUANG ; Guofeng PAN
Cancer Research and Clinic 2014;26(5):332-335
Objective To evaluate the safety,tumor radical and early postoperative efficacy through comparison of laparoscopic gastric D2 radical surgery with traditional open gastric D2 radical surgery.Methods 254 patients with upper stomach cancer underwent surgery were selected,132 cases using conventional open gastrectomy (the traditional laparotomy group),122 patients underwent laparoscopic radical gastrectomy (laparoscopic surgery group).Laparoscopic surgery group with traditional open surgery group had no statistically significant differences in gender,age,tumor location,histological type and TNM staging.Results Open surgery group and laparoscopic surgery group had statistically significant differences in operative time [(235.78±31.56) min,(256.43±54.08) min,P < 0.001],blood loss [(326.69±89.73) ml,(158.31±62.98) ml,P < 0.001],incision length [(16.53±2.34) cm,(5.51±1.15) cm,P < 0.001],gastrointestinal recovery time [(4.22±0.91) d,(3.31±0.83) d,P < 0.001],first time eating liquid [(5.78±0.95) d,(5.56±0.78) d,P < 0.001] and postoperative hospital stay [(12.62±2.89) d,(11.18±1.78) d,P < 0.001].The total number of lymph node dissection and complications was not statistically significant.Conclusions Laparoscopic gastric D2 radical surgery is a safe,minimally invasive surgical method.Laparoscopic gastric D2 radical surgery has the same lymph node dissection and good early outcome compared with the traditional gastric D2 radical surgery,but postoperative recovery fast and less invasive.
3.Roles of microRNAs in the tumor progression promoted by cancer-associated fibroblasts
Chinese Journal of Cancer Biotherapy 2019;26(11):1181-1188
Cancer-associated fibroblasts (CAFs) are one of the major cellularcomponents in tumor microenvironment (TME), which play an important role in cancer progression. MicroRNAs (miRNAs) could participate in the process of CAFs, transformation and metabolism reprogramming, affect the stemness of CAFs, and regulate CAFs-mediated tumor cell proliferation, invasion and chemotherapy resistance; and studies have shown that miRNAs play an important role in CAFs formation and the regulation of CAFs on tumors. The miRNAs released by CAFs can be used as reference indicators for tumor diagnosis, prognosis and drug selection. Thus, exploring the role of miRNAs in the interaction between CAFs and tumor cells and underlining the mechanism, is of great significancefor understanding the occurrence and development of tumors, as well as providing novel strategy for cancer treatment. This review will summarize the role of miRNAs in the formation of CAFs and the regulation of CAFs on tumor cells.
4.Based on Wnt/β-Catenin Signal Pathway to Explore the Mechanism of Tongluotangtai Recipe on GK Rats with Diabetes Peripheral Neuropathy
Jiushu YUAN ; Xueru WANG ; Susu HUANG ; Jie XU ; Huixuan ZHANG ; Hong GAO ; Lian DU ; Chunguang XIE
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(9):2950-2958
Objective Exploring the effect of Tong luo tang tai(TLTT)on diabetic peripheral neuropathy(DPN)in GK rats with Wnt/β-The influence of the catenin signaling pathway.Methods Fifty GK rats were randomly divided into model group,TLTT high,medium,and low dose groups,and Western medicine group,with 10 rats in each group.Another 10 wistar rats were selected as the normal group.Except for the normal group,all other groups were fed with high fat to prepare DPN rat models.After 15 weeks,the DPN model was successfully prepared,and the rats in each group were treated by gavage.The high,medium,and low dose groups of TLTT were given traditional Chinese medicine TLTT 28 g·kg-1,14 g·kg-1,and 7 g·kg-1,respectively.The western medicine group was given metformin 100 mg·kg-1 and mecobalamin 0.2 mg·kg-1 by gavage.Rats in each group were administered once a day for 8 consecutive weeks.The general state,fasting blood sugar(FBS),thermal contraction latency(TWL),motor nerve conduction velocity(MNCV),and pathological changes in the sciatic nerve tissue were observed under transmission electron microscopy(Real time PCR)Western blot detection of wingless MMTV integration site family member 3A(Wnt3a)β Catenin(β-Catenin,Glycogen Synthesis Kinase-3β Glycogen synthesis kinase-3β,GSK-3β)MRNA and protein expression levels of antagonists(WNT inhibitor factor-1,Wif-1)on the Wnt signaling pathway.Results Compared with the normal group,the model group showed poorer general condition and significant pathological ultrastructural changes in the sciatic nerve.Its FBS level increased(P<0.01),TWL level decreased(P<0.01),and MNCV significantly slowed down(P<0.01).The model group had Wnt3a β-Catenin,GSK-3β MRNA and protein expression levels decreased(P<0.05),while Wif-1 mRNA and protein expression levels increased(P<0.01).After drug intervention,compared with the model group,the general condition and pathological ultrastructure of the sciatic nerve were improved in the TLTT high,medium,low,dose,and Western medicine groups,with a decrease in FBS levels(P<0.01)and an increase in TWL levels(P<0.05).The MNCV of each TLTT dose group and Western medicine group was significantly improved(P<0.01).The Wnt3amRNA of the TLTT high-dose group and Western medicine group was significantly increased(P<0.05),while the Wif-1mRNA of the TLTT high-dose group and Western medicine group was significantly reduced(P<0.05),There was a significant increase in Wnt3 protein in the high-dose and Western medicine groups of TLTT(P<0.01),as well as in the high-dose,medium,and low-dose TLTT and western medicine groups β-Catenin protein significantly increased(P<0.01,P<0.05),with high,medium,and low doses of TLTT and Western medicine group GSK-3β The protein significantly increased(P<0.01,P<0.05),while the Wif-1 protein significantly decreased(P<0.01,P<0.05)in the high and medium dose TTLTT and western medicine groups.Conclusion Tongluo Tangtai can alleviate sciatic nerve injury in DPN to a certain extent,and its mechanism may be related to the activation of Wnt/β,the catenin signaling pathway is involved.
5.miR-101 inhibits migration and invasion of non-small cell lung cancer by targeting fibroblast growth factor 2
GUO Xueru ; ZHANG Qicheng ; CAO Limin ; XU Ke
Chinese Journal of Cancer Biotherapy 2020;27(9):984-991
[Abstract] Objective: To investigate the molecular mechanism of microRNA-101 (miR-101) inhibiting the migration and invasion of non-small cell lung cancer (NSCLC) via targeting fibroblast growth factor 2 (FGF2). Methods: qPCR was used to detect the expression levels of miR-101 and FGF2 in human normal lung epithelial BEAS-2B cells and NSCLC cell lines (A549, H661 and SK-MES-1) as well as A549 cells after transfection. MiR-NC, miR-101 mimics, miR-IN-NC, miR-101 inhibitor or pcDNA-3.1 empty plasmid, pcDNA-FGF2 were respectively transfected into A549 cells. Wound healing assay and Transwell assay were used to examine the effects of overexpression of miR-101 and FGF2 on the migration and invasion of A549 cells. Western blotting(WB) was used to detect the expression levels of FGF2, E-cadherin, N-cadherin, Vimentin, ERK1/2 and p-ERK1/2 in A549 cells in each group. Results: The expression level of miR-101 in NSCLC cell lines were significantly lower than that in normal lung epithelial cells (all P<0.05), while the expression level in A549 cells was the lowest. Overexpression of miR-101 significantly inhibited the migration (P<0.05) and invasion (P<0.01) of A549 cells, increased the expression level of E-cadherin but decreased the expression level of Vimentin (P<0.05),N-cadherin (P<0.01) and p-ERK1/2 (P<0.05). Inhibition of miR-101 significantly enhanced the invasion and migration of A549 cells (all P<0.05), decreased the expression level of E-cadherin but increased the expression levels of Vimentin, N-cadherin and p-ERK1/2
(all P<0.05). The results of WB and Dual-luciferase reporter gene assay verified that FGF2 is a direct target gene of miR-101, and over‐expression of FGF2 significantly enhanced the invasion and migration of A549 cells (all P<0.01), decreased the expression of E-cadherin (P<0.01) but increased the expressions of Vimentin (P<0.01), N-cadherin (P<0.05) and p-ERK1/2 (P<0.01). Compared with the FGF2 overexpression alone group, co-overexpression of miR-101 and FGF2 significantly reduced the invasion and migration of A549
cells (all P<0.01), increased the expression of E-cadherin (P<0.01), and decreased the expressions of Vimentin (P<0.01), N-cadherin
(P<0.05) and p-ERK1/2 (P<0.01). Conclusion: By targeting FGF2, miR-101 inhibits the invasion and migration of NSCLC cells through suppressing the epithelial-mesenchymal transition (EMT) and ERK signaling pathway.
6.Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy.
Yue ZHANG ; Jingwen GAO ; Na LI ; Peng XU ; Shimeng QU ; Jinqian CHENG ; Mingrui WANG ; Xueru LI ; Yaheng SONG ; Fan XIAO ; Xinyu YANG ; Jihong LIU ; Hao HONG ; Ronghao MU ; Xiaotian LI ; Youmei WANG ; Hui XU ; Yuan XIE ; Tianming GAO ; Guangji WANG ; Jiye AA
Acta Pharmaceutica Sinica B 2024;14(2):667-681
Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.