1.The expression of PIWI protein in tissue of human colon cancer and its clinical significance
Juan LI ; Xiaoying SHEN ; Shizhang ZHU ; Wei WANG ; Ximei CHEN ; Changqing YANG ; Hengjun GAO
Chinese Journal of Digestion 2011;31(4):243-248
Objective To study the expression of PIWIL1, PIWIL3 and PIWIL4 in human colon cancer and its clinical significance. Methods We collected cancerous tissues and its adjacent tissues of 106 patients with colon cancer, two tissue microarrays were constructed, with 62 and 150 points respectively. We studied the expression of PIWIL1, PIWIL3 and PIWIL4 through immunohistochemistry. Results The expression of PIWIL1, PIWIL3 and PIWIL4 were significantly higher in cancerous tissues than those in adjacent tissues (P<0. 01). In cancerous tissues and its adjacent tissues, postive correlation were seen among PIWIL1, PIWIL3 and PIWIL4 expression (P<0. 01). PIWIL1 expression was significant higher in low differentiation group than that in high differentiation group (t =- 2. 840, P<0.01 ). PIWIL3 expression was higher in high clinical stage than that in low clinical stage (F= 3. 112, P<0.05). The expression of PIWIL3 and PIWIL4 were significantly higher in patients with colon cancer with distant metastasis than those without distant metastasis (t= -3. 349, P<0.01 ; t = - 2. 168, P<0. 05). PIWIL3 and PIWIL4 expression were correlated with occurring of colon cancer (P<0. 01). Conclusions The expressions of PIWIL1,PIWIL3 and PIWIL4 in colon cancer were correlated with the differentiation, clinical stage and distant metastasis of colon cancer. PIWIL3 and PIWIL4 expression were two independent related factors of occurring of colon cancer, which would be furtherly investigated to be served as novel markers for early diagnosis and promising molecular targets for colon cancer therapy.
2.Clinical analysis of 110 cases of infectious mononucleosis in children
Hua WANG ; Xiaodong LIU ; Chaofan XU ; Shizhang CHENG
Chinese Journal of Infection and Chemotherapy 2019;19(1):23-26
Objective To analyze the clinical characteristics of 110 cases of infectious mononucleosis in children. Methods The clinical data of 110 children with infectious mononucleosis in the period from January 2015 to January 2018 were analyzed retrospectively. Results The 110 patients included 74 males(67.3%)and 36 females(32.7%). The male to female ratio was 2.1:1.The age distribution: 2~<3 years old, 29 cases(26.4%); 3-6 years old, 67 cases(60.9%);>6-13 years old, 14 cases(12.7%).The main symptoms and signs included fever in 101 cases(91.8%), pharyngitis in 100 cases(90.9%), lymphadenomegaly in 95 cases(86.4%), eyelid edema in 79 cases(71.8%), splenomegaly in 55 cases(50.0%), and liver enlargement in 37 cases(33.6%).The complications were pneumonia in 61 cases(55.5%), myocardial damage in 53 cases(48.2%), neutropenia in 35 cases(31.8%), and thrombocytopenic purpura in 4 cases(3.6%). The prevalence of IgM antibody against Epstein-Barr virus capsid antigen was43.6%. The prevalence of IgM antibody against Epstein-Barr virus early antigen was 31.8%. The positive rate of IgG antibody against Epstein-Barr virus nuclear antigen was 56.4%. The prevalence of atypical lymphocytes in peripheral blood was 46.4%.Conclusions Infectious mononucleosis in children is more common in males and during the period from 3 to 6 years of age. The clinical symptoms include pneumonia and myocardial damage. Epstein-Barr virus detection and serological assay are helpful for diagnosis.
3.The initial observation of adenovirus vector-mediated herpes simplex virus-thymidine kinase gene/ganciclovir system and photodynamic therapy for oral malignant tumor treatments.
Shizhang CHEN ; Yansheng ZHANG ; Zhong FAN ; Weidi LI ; Ying GUO ; Xiao WANG ; Jianfei CHEN ; Ning LI
West China Journal of Stomatology 2011;29(6):610-617
OBJECTIVETo evaluate the method of adenovirus vector-mediated herpes simplex virus-thymidine kinase gene (ADV-TK)/ganciclovir(GCV) system and photodynamic therapy(PDT) for treating the oral malignant tumor.
METHODSTen patients who were suffering from oral malignant tumor of the different positions were selected, and injected with the hematoporphyrin derivative (HPD), irradiated by picking the corresponding laser frequency, and injected the ADV-TK gene into the tumor body and periphery. By the imaging and the hemodynamics analysis, the clinical efficacy after infusing vein with GCV was assessed.
RESULTSAfter the combination method treatments, patients' tumors appeared clear shrinkage or complete extinction. There was obvious fall of the blood flow volume in the tumor body. Imaging results showed significantly differences. So it was a perfect and effective treatment.
CONCLUSIONThere are many advantages to apply the ADV-TK/GCV system and PDT treatment on the oral malignant tumor, minimal side effects and greater clinical security. It is a safe and credible therapy which can be offered for curing the oral malignant tumor systematically.
Adenoviridae ; Ganciclovir ; Genetic Vectors ; Humans ; Neoplasms ; Photochemotherapy ; Simplexvirus ; Thymidine Kinase
4.Involvement of fascin-1-mediated autophagy in the biological behavioral of endometrial cells.
Xiaomei LUO ; Wei CHENG ; Shizhang WANG ; Zhihong CHEN
Journal of Central South University(Medical Sciences) 2018;43(9):957-963
To explore the mechanism for the role of autophagy in endometriosis, and to provide a theoretical basis for prevention and treatment of endometriosis.
Methods: The endometrial CRL-7566 cells were treated with ATG5 siRNA, autophagic activator rapamycin and autophagic inhibitor 3-MA, respectively. The cell proliferation and invasion were detected by clonal formation, cell growth curve and MTT assay. The clinical specimens of endometriosis were collected from 20 cases. The expression of autophagy marker LC3II and autophagy substrate protein P62 were detected.
Results: Rapamycin inhibited the proliferation and clonal formation of CRL-7566 cells, while autophagy inhibitor 3-MA and ATG5 siRNA showed opposite effect. Moreover, rapamycin inhibited filopodia growth in endometriosis, whereas overexpression of filopodia-relevant protein fascin-1 inhibited the decrease in invasiveness caused by rapamycin. In clinical samples, we also found a significant decrease of LC3II while an increase in P62 compared with the control group.
Conclusion: Autophagy inhibition may contribute to an increase in endometrial cell proliferation and invasiveness. Autophagy activation could be a potential strategy for endometriosis therapy.
Autophagy
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drug effects
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genetics
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Carrier Proteins
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genetics
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metabolism
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Cell Line
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Cell Proliferation
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drug effects
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Endometriosis
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physiopathology
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Endometrium
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cytology
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Female
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Gene Expression Regulation
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Humans
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Microfilament Proteins
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genetics
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metabolism
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Microtubule-Associated Proteins
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genetics
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RNA-Binding Proteins
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genetics
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Sirolimus
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pharmacology
5.Inhibiting silence information regulator 2 and glutaminase in the amygdala can improve social behavior in autistic rats.
Xiaoxia ZHANG ; Shizhang LIU ; Xiaomei LIU ; Jieying WANG
Journal of Zhejiang University. Medical sciences 2022;51(6):707-715
OBJECTIVE:
To investigate the underlying molecular mechanisms by which silence information regulator (SIRT) 2 and glutaminase (GLS) in the amygdala regulate social behaviors in autistic rats.
METHODS:
Rat models of autism were established by maternal sodium valproic acid (VPA) exposure in wild-type rats and SIRT2-knockout ( SIRT2 -/-) rats. Glutamate (Glu) content, brain weight, and expression levels of SIRT2, GLS proteins and apoptosis-associated proteins in rat amygdala at different developmental stages were examined, and the social behaviors of VPA rats were assessed by a three-chamber test. Then, lentiviral overexpression or interference vectors of GLS were injected into the amygdala of VPA rats. Brain weight, Glu content and expression level of GLS protein were measured, and the social behaviors assessed.
RESULTS:
Brain weight, amygdala Glu content and the levels of SIRT2, GLS protein and pro-apoptotic protein caspase-3 in the amygdala were increased in VPA rats, while the level of anti-apoptotic protein Bcl-2 was decreased (all P<0.01). Compared with the wild-type rats, SIRT2 -/- rats displayed decreased expression of SIRT2 and GLS proteins in the amygdala, reduced Glu content, and improved social dysfunction (all P<0.01). Overexpression of GLS increased brain weight and Glu content, and aggravated social dysfunction in VPA rats (all P<0.01). Knockdown of GLS decreased brain weight and Glu content, and improved social dysfunction in VPA rats (all P<0.01).
CONCLUSIONS
The glutamate circulatory system in the amygdala of VPA induced autistic rats is abnormal. This is associated with the upregulation of SIRT2 expression and its induced increase of GLS production; knocking out SIRT2 gene or inhibiting the expression of GLS is helpful in maintaining the balanced glutamate cycle and in improving the social behavior disorder of rats.
Animals
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Rats
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Amygdala/metabolism*
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Autistic Disorder/metabolism*
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Behavior, Animal
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Disease Models, Animal
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Glutamates/metabolism*
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Glutaminase/metabolism*
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Sirtuin 2/metabolism*
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Social Behavior
6.Ameliorative Effect and Mechanism of Qingwen Baiduyin on Lipopolysaccharide-induced Acute Lung Injury
Ju YANG ; Zhao ZHANG ; Jiawei WANG ; Shuying XIE ; Pengyan LI ; Liwei LANG ; Shizhang WEI ; Haotian LI ; Manyi JING ; Yanling ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(15):1-13
To investigate the therapeutic effect and mechanism of Qingwen Baiduyin on acute lung injury (ALI) in mice induced by lipopolysaccharide (LPS). MethodA total of 144 C57BL/6 mice were randomly divided into the following groups: a normal group, a model group (LPS, 5 mg·kg-1), a dexamethasone group (5 mg·kg-1), and low-, medium-, and high-dose Qingwen Baiduyin groups (14.105, 28.21, 56.42 g·kg-1). The mice were treated once daily for 5 days. One hour after the final administration, the ALI model was established by intratracheal instillation of LPS, and samples were collected at 6 h and 24 h after modeling. The arterial blood gas index of mice was analyzed. The total protein content, total cell count, Evans blue dye (EBD) content, and lung tissue wet-to-dry weight ratio (W/D) of bronchoalveolar lavage fluid (BALF) were measured. Hematoxylin-eosin (HE) staining was performed to assess the pathological changes in mouse lung tissue. Western blot was used to detect the expression levels of key proteins in the Janus kinase 1/signal transducer and activator of transcription 1/interferon regulatory factor 1 (JAK1/STAT1/IRF1) signaling pathway in lung tissue. ResultCompared with the normal group, the model group showed reduced arterial oxygen pressure (pO2), oxygen saturation (SO2), and lung tissue W/D (P<0.05, P<0.01), increased carbon dioxide pressure (pCO2), total protein content, total cell count, EBD content, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), chemokine CXC ligand 1 (CXCL1), chemokine CXC ligand 2 (CXCL2), chemokine CXC ligand 9 (CXCL9), and chemokine CXC ligand 10 (CXCL10) content (P<0.05, P<0.01), thickening of the alveolar walls, fusion of alveolar cavities, and infiltration of inflammatory cells in lung tissue, increased proportion of M1 macrophage polarization and lung cell apoptosis (P<0.05), and increased protein expression levels of JAK1, phosphorylated JAK1 (p-JAK1), inducible nitric oxide synthase (iNOS), STAT1, phosphorylated STAT1 (p-STAT1), IRF1, gasdermin D (GSDMD), and mixed lineage kinase domain-like protein (MLKL) (P<0.05, P<0.01). Compared with the model group, Qingwen Baiduyin significantly increased pO2, SO2, and lung tissue W/D (P<0.05, P<0.01), improved the pathological changes in lung tissue, and reduced pCO2, total protein content, total cell count, EBD content, IFN-γ, TNF-α, IL-1β, CXCL1, CXCL2, CXCL9, and CXCL10 content, proportion of M1 macrophage polarization, and protein expression levels of JAK1, p-JAK1, iNOS, STAT1, p-STAT1, IRF1, GSDMD, and MLKL (P<0.05, P<0.01). ConclusionQingwen Baiduyin can improve the lung inflammatory response and reduce lung cell apoptosis in mice with ALI by inhibiting the JAK1/STAT1/IRF1 signaling pathway, thereby exerting a lung-protective effect.
7.Effect and Mechanism of Zuojinwan on DSS-induced Ulcerative Colitis
Zhao ZHANG ; Ju YANG ; Jiawei WANG ; Shuying XIE ; Wenbin WU ; Manyi JING ; Liwei LANG ; Haotian LI ; Shizhang WEI ; Jian WANG ; Yanling ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(16):1-11
ObjectiveTo explore the effect and mechanism of Zuojinwan (ZJW) in the treatment of ulcerative colitis (UC) through network pharmacology and experimental validation. MethodUsing network pharmacology and molecular docking, the active components and potential mechanism of ZJW in treating UC were preliminarily identified. Forty-eight male C57BL/6J mice were randomly divided into a normal group, a model group, a sulfasalazine group (300 mg·kg-1), and low-, medium-, and high-dose ZJW groups (1.82, 3.64, 7.28 g·kg-1). The UC model was induced by dextran sulfate sodium (DSS), and oral administration of drugs began on the third day of modeling, lasting for 7 days. The general condition of mice was observed daily, and the disease activity index (DAI) was evaluated. Hematoxylin-eosin (HE) staining was performed to observe histopathological changes in colon tissue. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in mouse serum. The molecular mechanism was validated using Western blot. ResultNetwork pharmacology predicted that the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway might be a key pathway in the regulation of UC by ZJW. Molecular docking results showed good binding ability between the key components of ZJW and core targets. Animal experiment results showed that compared with the normal group, the model group had shortened colon length (P<0.01), increased DAI scores, spleen index, colon tissue pathology scores, and levels of TNF-α and IL-6 in serum (P<0.05, P<0.01), increased PI3K, phosphorylated Akt (p-Akt), and B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax) expression in colon tissue (P<0.05, P<0.01), and decreased serum IL-10 levels and colon tissue Bcl-2 protein expression (P<0.01). Compared with the model group, the ZJW groups showed significant improvement in UC symptoms, relieved colon tissue pathological damage, downregulated levels of inflammatory cytokines TNF-α and IL-6 in serum (P<0.01), inhibited expression of PI3K, p-Akt, and Bax proteins in colon tissue (P<0.05, P<0.01), and increased serum IL-10 levels and colon tissue Bcl-2 protein expression (P<0.01), with the high-dose group showing the best effect. ConclusionZJW effectively alleviates DSS-induced UC, and its mechanism may be related to the inhibition of the PI3K/Akt signaling pathway and regulation of apoptosis-related protein expression.