1.Modified Xiaoyaosan Alleviates Depression-like Behaviors by Regulating Activation of Hippocampal Microglia Cells in Rat Model of Juvenile Depression
Jiayi SHI ; Yun XIANG ; Ziyang ZHOU ; Dahua WU ; Feng QIU ; Chang LEI ; Hongyu ZENG ; Kaimei TAN ; Hongqing ZHAO ; Dong YANG ; Yuhong WANG ; Pengxiao GUO ; Xiuli ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):46-56
ObjectiveTo investigate the mechanism of Baihuan Xiaoyao Decoction (Xiaoyaosan added with Lilii Bulbus and Albiziae Cortex) in alleviating depression-like behaviors of juvenile rats by regulating the polarization of microglia. MethodSixty juvenile SD rats were randomized into normal control, model, fluoxetine, and low-, medium-, and high-dose (5.36, 10.71, 21.42 g·kg-1, respectively) Baihuan Xiaoyao decoction groups. The rat model of juvenile depression was established by chronic unpredictable mild stress (CUMS). The sucrose preference test (SPT) was carried out to examine the sucrose preference of rats. Forced swimming test (FST) was carried out to measure the immobility time of rats. The open field test (OFT) was conducted to measure the total distance, the central distance, the number of horizontal crossings, and the frequency of rearing. Morris water maze (MWM) was used to measure the escape latency and the number of crossing the platform. The immunofluorescence assay was employed to detect the expression of inducible nitric oxide synthase (iNOS, the polarization marker of M1 microglia) and CD206 (the polarization marker of M2 microglia). Real-time polymerase chain reaction was employed to determine the mRNA levels of iNOS, CD206, pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6] and anti-inflammatory cytokines (IL-4 and IL-10) in the hippocampus. Western blotting was employed to determine the protein levels of iNOS and CD206 in the hippocampus. The levels of IL-4 and IL-6 in the hippocampus were detected by enzyme-linked immunosorbent assay. ResultCompared with the normal control group, the model rats showed a reduction in sucrose preference (P<0.05), an increase in immobility time (P<0.05), decreased motor and exploratory behaviors (P<0.05), and weakened learning and spatial memory (P<0.05). In addition, the model rats showed up-regulated mRNA and protein levels of iNOS and mRNA levels of IL-1β, IL-6, and TNF-α (P<0.05). Compared with the model group, Baihuan Xiaoyao decoction increased the sucrose preference value (P<0.05), shortened the immobility time (P<0.01), increased the motor and exploratory behaviors (P<0.05), and improved the learning and spatial memory (P<0.01). Furthermore, the decoction down-regulated the positive expression and protein level of iNOS, lowered the levels of TNF-α, IL-1β, and IL-6 (P<0.01), promoted the positive expression of CD206, and elevated the levels of IL-4 and IL-10 (P<0.01) in the hippocampus of the high dose group. Moreover, the high-dose Baihuan Xiaoyao decoction group had higher sucrose preference value (P<0.01), shorter immobility time (P<0.01), longer central distance (P<0.01), stronger learning and spatial memory (P<0.01), higher positive expression and protein level of iNOS (P<0.01), lower levels of TNF-α, IL-1β, and IL-6 (P<0.05, P<0.01), lower positive expression and mRNA level of iNOS (P<0.05), and higher levels of IL-4 and IL-10 (P<0.05, P<0.01) than the fluoxetine group. ConclusionBaihuan Xiaoyao decoction can improve the depression-like behavior of juvenile rats by inhibiting the M1 polarization and promoting the M2 polarization of microglia in the hippocampus.
2.Role of C-Myc in the Development and Progression of Pancreatic Cancer
Junyi ZHU ; Qimin YU ; Jiana SHI ; Shuilian ZHENG ; Ping HUANG ; Xiurong WU ; Xiuli YANG
Chinese Journal of Modern Applied Pharmacy 2024;41(11):1577-1590
Pancreatic cancer induced by mutation KRAS exhibited a higher risk of incidence, recurrence and mortality. C-Myc is downstream of KRAS and can be involved in the regulation of multiple oncogenic pathways and signaling pathways in pancreatic cancer. Over expressing of C-Myc promotes glycolysis and glutamine uptake in pancreatic cancer cells, promotes cell metabolism and proliferation, is an important factor driving the progress and maintenance of pancreatic cancer, and is related to chemotherapy and immunotherapy drug resistance. C-Myc also interacts with cell cyclin-dependent kinase(CDK) and non-coding RNA to regulate the proliferation, development and metastasis of pancreatic cancer. Therefore, targeting C-Myc was regarded as an effective strategy for the treatment of pancreatic cancer. The activation of C-Myc depends on heterodimerization with its partner MAX and thereby paly a role through binding to the canonical E-Box sequence 5’-CACGTG-3’. Researches showed direct targeting of C-Myc can inhibit the growth of pancreatic carcinoma,such as promoting the degradation of C-Myc, inhibiting the binding of C-Myc/MAX and blocking the binding of C-Myc/MAX to E-box. However, direct targeting has been proved challenging because of its special protein structure. Indirect targeting of C-Myc provided a new strategy for the treatment of pancreatic cancer. C-Myc can be indirected targeting through inhibiting transcription and translation of C-Myc, C-Myc-MAX heterodimerization and promote the ubiquitination and degradation of C-Myc, thus affects the occurrence, development and metastasis of pancreatic cancer.
3.Poor sleep quality contributes to occurrence of posttraumatic stress disorder in trauma patients
Ping YUAN ; Xiuli HU ; Guojia QI ; Xiu DAI ; Xiangyuan CHU ; Weihang CHEN ; Xiuquan SHI
Journal of Southern Medical University 2024;44(6):1166-1172
Objective To evaluate the impact of poor sleep quality on occurrence of post-traumatic stress disorder(PTSD)in trauma patients.Methods We prospectively recruited 256 trauma patients hospitalized in 4 general hospitals in Zunyi during the period from October,2021 to November,2022,and 226 of the participants completed the PTSD survey and assessment.The patients'sleep quality within a month before trauma was estimated using Pittsburgh Sleep Quality Index(PSQI),and their sleep quality within 7 days after admission was monitored by smart bracelet sleep monitoring;the PTSD Checklist-Civilian Version(PCL-C)was used to detect the occurrence of PTSD during the follow-up.Results The detection rate of PTSD in the patients was 19.47%at 1 month and 17.61%at 3 months after trauma.The patients who developed PTSD had poorer sleep quality before the trauma,as shown by significantly higher PSQI scale scores(P<0.001),than those without PTSD,and they showed a sleep abnormality rate as high as 72.73%prior to PTSD onset.Within 7 days after admission,the patients developing PTSD had lower sleep quality scores with more frequent night awakenings(P<0.05).A 1 month and 3 months after trauma,the patients with PTSD had significantly higher PSQI scores than those without PTSD(P<0.05).Conclusion PTSD is more likely to occur in trauma patients with poor sleep quality before trauma.
4.Analysis of 32 cases of appendectomy after endoscopic retrograde appendicitis therapy in children
Lu YANG ; Junjie XU ; Shuai CHEN ; Shisong ZHANG ; Yumeng ZHANG ; Meng SHI ; Lijun ZHANG ; Xiuli LIU ; Xuxia WEI ; Zhongtao GAI
Chinese Pediatric Emergency Medicine 2024;31(7):518-522
Objective:To investigate the related risk factors of surgical appendectomy after endoscopic retrograde appendicitis therapy (ERAT) in children.Methods:From September 2019 to November 2023 at the Children's Hospital Affiliated to Shandong University,the data from all related children with appendectomy after ERAT were analyzed. The general situation and main clinical manifestations of the children were collected. According to the effect of ERAT,the patients were divided into transfer to surgical group and appendicitis recurrence group by the reasons and time of transfer to surgical treatment. The indexes such as ERAT and reoperation process and pathological types of appendix after operation were collected,and the clinical experience was summarized.Results:Among the 242 children who underwent ERAT,32 cases underwent appendectomy again,including 19 males and 13 females,with an average age of(9.16±2.77)years,and the reoperation rate was 13.2%. The clinical manifestation was abdominal pain (32 cases,100.0%),mainly right lower abdominal pain (28 cases,87.5%),and the main duration was less than 3 months (30 cases,93.8%). Abdominal ultrasound or CT before ERAT mainly indicated appendicitis (11 cases,34.4%) and appendicitis complicated with appendiceal calculus (11 cases,34.4%). There were 9 children in transferred to surgical group,of which 5 cases were transferred to surgery because of ERAT intubation failure,and 4 cases were transferred to surgery because of appendix perforation or abscess. Postoperative pathology showed acute suppurative appendicitis in 5 cases and acute gangrenous appendicitis in 4 cases. There were 23 children in appendicitis recurrence group,whose abdominal pain was relieved after ERAT,but their symptoms were repeated after discharge. After clinical evaluation,they were diagnosed as recurrent appendicitis and underwent surgical appendectomy. Most of them were reoperated within 6 months after ERAT (21 cases,91.3%).Postoperative pathology was mainly chronic appendicitis (10 cases,43.5%).Conclusion:Acute suppurative appendicitis and acute gangrenous appendicitis are prone to catheterization or endoscopic failure during ERAT,and there is a high risk of surgical transfer. ERAT may relieve the symptoms of chronic appendicitis in children. If the symptoms are repeated,surgery is still needed to remove the appendix.
5.The effect of miR-143-3p on pyroptosis of ulcerative colitis cells by regulating TLR2/NF-κB/NLRP3
Xiuli SHI ; Jiaqi CHEN ; Fan ZHU ; Juan ZENG ; Na WU
The Journal of Practical Medicine 2024;40(15):2056-2062
Objective To study the effect of miR-143-3p on pyroptosis of HCT-116 cells induced by LPS+ATP.Methods The targeting relationship between miR-143-3 p and TLR2 gene was detected by dual luciferase.The pyroptosis model was established after transfection of miR-143-3p mimic.Cell apoptosis was detected by flow cytometry,and the activity of Caspase-1 and LDH was detected by biochemical method.The levels of IL-1β and IL-18 were detected by ELISA.The mRNA levels of NF-κB,TLR2,NLRP3 and GSDMD were detected by q-PCR.The expression of NLRP3 and ASC was detected by immunofluorescence.The protein expressions of TLR2,GS-DMD,p-NF-κB p65 and cleave Caspase-1 were detected by Western blot.Results Dual luciferase assay showed that miR-143-3p targeted TLR2 expression.The expressions of NF-κB,TLR2,NLRP3,GSDMD mRNA and TLR2,GSDMD,p-NF-κB p65,cleave Caspase-1,ASC,NLRP3 protein in miR-143-3p mimic group and si TLR2 group were lower than those in model group.The activity of Caspase-1 and the content of LDH,IL-1β and IL-18 decreased.Conclusion miR-143-3p regulates pyroptosis of ulcerative colitis cells by targeting TLR2 gene and regulating NF-κB/NLRP3/Caspase-1 signaling pathway.
6.Poor sleep quality contributes to occurrence of posttraumatic stress disorder in trauma patients
Ping YUAN ; Xiuli HU ; Guojia QI ; Xiu DAI ; Xiangyuan CHU ; Weihang CHEN ; Xiuquan SHI
Journal of Southern Medical University 2024;44(6):1166-1172
Objective To evaluate the impact of poor sleep quality on occurrence of post-traumatic stress disorder(PTSD)in trauma patients.Methods We prospectively recruited 256 trauma patients hospitalized in 4 general hospitals in Zunyi during the period from October,2021 to November,2022,and 226 of the participants completed the PTSD survey and assessment.The patients'sleep quality within a month before trauma was estimated using Pittsburgh Sleep Quality Index(PSQI),and their sleep quality within 7 days after admission was monitored by smart bracelet sleep monitoring;the PTSD Checklist-Civilian Version(PCL-C)was used to detect the occurrence of PTSD during the follow-up.Results The detection rate of PTSD in the patients was 19.47%at 1 month and 17.61%at 3 months after trauma.The patients who developed PTSD had poorer sleep quality before the trauma,as shown by significantly higher PSQI scale scores(P<0.001),than those without PTSD,and they showed a sleep abnormality rate as high as 72.73%prior to PTSD onset.Within 7 days after admission,the patients developing PTSD had lower sleep quality scores with more frequent night awakenings(P<0.05).A 1 month and 3 months after trauma,the patients with PTSD had significantly higher PSQI scores than those without PTSD(P<0.05).Conclusion PTSD is more likely to occur in trauma patients with poor sleep quality before trauma.
7.Establishment of SKH-1 mouse models of implanted B16F10 melanoma
Fuhe ZHANG ; Lei SHI ; Min LUO ; Pei LIU ; Qing FAN ; Xiuli WANG
Chinese Journal of Dermatology 2023;56(10):953-956
Objective:To establish SKH-1 mouse models of subcutaneously transplanted B16F10 melanoma and of lung-metastasized B16F10 melanoma.Methods:Seven SKH-1 mice and seven C57BL/6 mice were subcutaneously inoculated with 5 × 10 6 B16F10 cells on the back, and the survival duration of mice was observed and recorded. The tumor volume was measured by using a precision vernier caliper every 3 days. Mice were considered as ethically dead when the tumor length was more than 15 mm, or when cachexia or ulceration occurred. In addition, 5 SKH-1 mice were injected with 5 × 10 6 B16F10 cells via the tail vein, and the activity, nutritional status and survival duration of the mice were observed. The mice were sacrificed after the observation, and the lungs were weighed after dissection. Histopathological examination was performed on the lungs of all mice. All the experiments were repeated 3 times. Results:On day 6 after the subcutaneous inoculation, black spots appeared at the skin inoculation site in the SKH-1 mice, and gradually developed into round black nodules, then progressed into ulcerative and hemorrhagic tumors until the death of mice, and the time to ethical death ranged from 20 to 33 days. In the C57BL/6 mice, small black nodules measuring 2 - 3 mm in length appeared at the skin inoculation site on day 4 after the subcutaneous inoculation, and the time to ethical death ranged from 12 to 18 days. The survival duration of SKH-1 mice was 26.57 ± 4.03, 27.86 ± 4.53, and 27.43 ± 5.32 days in the 3 times of experiments respectively, and there was no significant difference ( F = 0.14, P = 0.87) ; on day 27 after the subcutaneous inoculation, the tumor volume was 1 367.9 ± 150.2, 1 452.0 ± 50.1, and 1 490.3 ± 69.0 mm 3 in the 3 times of experiments respectively, and there was also no significant difference ( F = 0.92, P = 0.46). SKH-1 mice had shown decreased activity and anorexia since day 25 after tail vein injections of B16F10 cells, and dullness, emaciation, ascites and death had been observed since day 31, and the time to ethical death ranged from 31 to 40 days; multiple black nodules were observed in the lung after dissection, and the survival duration was 34.20 ± 2.58, 36.40 ± 2.60, and 34.80 ± 2.38 days in the 3 times of experiments respectively, which did not differ among the 3 times of experiments ( F = 1.01, P = 0.39) ; there was also no significant difference in the lung weight among the 3 times of experiments (156.1 ± 18.5, 164.0 ± 19.6, and 172.0 ± 17.2 mg, respectively, F = 3.18, P = 0.72). All the mice developed tumors, and histopathological examinations of subcutaneous tumor masses and lung tissues confirmed the diagnosis of melanoma. Conclusion:In this experiment, the SKH-1 mouse models of subcutaneously transplanted B16F10 melanoma and of lung-metastasized B16F10 melanoma were successfully established, which showed high tumor formation rates and favorable stability in tumor formation.
8.Fibroblast growth factor 23 and cerebrovascular diseases
Meili SHI ; Guilan LI ; Xiuli LI
International Journal of Cerebrovascular Diseases 2023;31(2):141-145
Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays a central role in the regulation of calcium, phosphorus and active vitamin D levels. Recent studies have shown that high FGF23 is associated with cardiocerebrovascular diseases. This article reviews the correlation between FGF23 and cerebrovascular diseases.
9.Generation of αGal-enhanced bifunctional tumor vaccine.
Jian HE ; Yu HUO ; Zhikun ZHANG ; Yiqun LUO ; Xiuli LIU ; Qiaoying CHEN ; Pan WU ; Wei SHI ; Tao WU ; Chao TANG ; Huixue WANG ; Lan LI ; Xiyu LIU ; Yong HUANG ; Yongxiang ZHAO ; Lu GAN ; Bing WANG ; Liping ZHONG
Acta Pharmaceutica Sinica B 2022;12(7):3177-3186
Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis and high mortality. In this study, we demonstrated a novel vaccine targeting HCC and tumor neovascular endothelial cells by fusing recombinant MHCC97H cells expressing porcine α-1,3-galactose epitopes (αGal) and endorphin extracellular domains (END) with dendritic cells (DCs) from healthy volunteers. END+/Gal+-MHCC97H/DC fusion cells induced cytotoxic T lymphocytes (CTLs) and secretion of interferon-gamma (IFN-γ). CTLs targeted cells expressing αGal and END and tumor angiogenesis. The fused cell vaccine can effectively inhibit tumor growth and prolong the survival time of human hepatoma mice, indicating the high clinical potential of this new cell based vaccine.
10.Effect of Zishen Huoxue Prescription on Regulation of Mitophagy and Neurogenesis in Hippocampal CA1 Region of Vascular Dementia Rats
Ziting ZHAO ; Dahua WU ; Xiuli ZHANG ; Le XIE ; Tonghe LIU ; Shanshan ZENG ; Jiayi SHI ; Ting YAO ; Yao XIE ; Yinchen LI
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(20):45-52
ObjectiveTo investigate the effect of Zishen Huoxue prescription on promoting neurogenesis in hippocampal CA1 region of vascular dementia (VD) rats by regulating mitophagy. MethodThe 2-VO method was used to establish the VD rat model and 60 SD rats were randomly divided into sham operation group, model group, donepezil hydrochloride group, and Zishen Huoxue prescription low-dose(8.9 g·kg-1), medium-dose(17.8 g·kg-1) and high-dose(35.6 g·kg-1) groups. Morris water maze test was performed to detect the escape latency and the number of crossing platform in each group. The expression of phosphatase and tensin homology-induced kinase 1 (PINK1) and Parkinson protein (Parkin) mRNA in hippocampal CA1 region was detected by Real-time fluorescent quantitative polymerase chain reaction(Real-time PCR). Western blot was used to determine the expression of mitochondrial autophagy signaling pathway-related proteins Parkin, prohibitin 2 (PHB2), mitofusin 2 (Mfn2) and dynamin-related protein 1 (Drp1) in hippocampal CA1 region. The neurogenesis in hippocampal CA1 region was tested by Brdu method. ResultCompared with the conditions in the sham operation group, the learning and spatial memory abilities of the model group were decreased (P<0.05), with damaged mitochondrial structure and autolysosome formation in the hippocampal CA1 region. The expressions of Parkin, Pink1 mRNA and Parkin, PHB2, and Drp1 proteins were up-regulated (P<0.05), while the expression of Mfn2 protein and the neuronal regeneration in hippocampal CA1 region were reduced (P<0.05, P<0.05). Compared with the conditions in the model group, Zishen Huoxue prescription enhanced the learning and spatial memory abilities of VD rats (P<0.05), increased the number of autophagosomes in hippocampal CA1 region and improved the mitochondrial structure. The expression of Parkin, Pink1 mRNA and Parkin, PHB2, and Drp1 proteins in hippocampal CA1 region was up-regulated (P<0.05, P<0.01)while the expression of Mfn2 protein was down-regulated(P<0.05, P<0.01). The number of new neurons in hippocampal CA1 region was also increased(P<0.05, P<0.01). ConclusionThe promoting effect of Zishen Huoxue prescription on the neurogenesis in hippocampal CA1 region of VD rats was related to the mitophagy mediated by Pink1/Parkin signaling pathway.


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