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30 January 2024, Volume 36 Issue 1
肝细胞核因子-1b在糜烂性毒剂2-氯乙基乙基硫醚诱导急性肺支气管上皮细胞损伤中的作用及其机制
KONG Deqin, LIU Sijia, LIU Jianhao, MA Yao, MA Chengfei, ZHAO Yushun, ZHOU Jiaheng, SHI Minjie, LI Jia, LIU Jiangzheng
2024, 36(1):  1-8.  doi:10.3969/j.issn.1004-616x.2024.01.001
Abstract ( 195 )   PDF (8337KB) ( 339 )  
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OBJECTIVE: To investigate the involvement of hepatocyte nuclear factor-1b(HNF-1b) in human lung bronchial epithelial cell injury induced by a blister agent, 2-chloroethyl ethyl sulfide(CEES).METHODS: The human BEAS-2B cells were treated in culture with various concentrations(0, 0.4, 0.6, 0.8, 1.0 and 1.2 mmol/L) of CEES for 24 h. The CCK-8 method was used to detect cell viability, and cell morphology was observed under light microscope. The DCFH-DA and MitoSOX fluorescent probes were used to detect total reactive oxygen species(ROS) and mitochondrial ROS levels, respectively. The protein expression of HNF-1b was assessed by Western blot. A BEAS-2B cell line which overexpresses HNF-1b was constructed by lentiviral infection. After exposure to 1 mmol/L CEES for 24 h, cell viability was determined by the CCK-8 method; apoptosis rate was detected by Annexin V-FITC/PI double staining method; mitochondrial ROS and whole-cell ROS levels were measured by MitoSOX and DHE probes, and mitochondrial membrane potential was detected by JC-1 staining. RESULTS: After exposure of BEAS-2B to 0.6-1.2 mmol/L CEES and compared to the controls, cell viability was reduced(P<0.01), cell morphology showed damage, the levels of total ROS and mitochondrial ROS were increased(P<0.01), and HNF-1b protein expression was significantly down-regulated(P<0.01). After exposure of the cells with over-expressed HNF-1b, the cell viability was significantly increased(P<0.01), apoptosis rate was decreased(P<0.01), mitochondrial membrane potential damage was relieved, and the levels of mitochondrial ROS and total whole-cell ROS were significantly decreased(P<0.01). CONCLUSION: Exposure of the regular BEAS-2B cells to CEES reduced the expression of HNF-1b and caused extensive damage. However, overexpression of HNF-1b in the BEAS-2B cells reduced the CEES-induced cellular damage, apoptosis and mitochondrial dysfunction. These results suggest that the protective effect of HNF-1b may mediated by antioxidation, and activation of HNF-1b may be a new strategy for the treatment of blister agent toxicity.
自噬在α粒子辐射诱发人支气管上皮细胞恶性转化中的作用
YANG Li, SHAO Shuai, WU Yunyun, WANG Chengfang, QU Gonglin, YAN Haoyu, GOU Qiao
2024, 36(1):  9-15,20.  doi:10.3969/j.issn.1004-616x.2024.01.002
Abstract ( 160 )   PDF (5141KB) ( 278 )  
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OBJECTIVE: To investigate the role of autophagy in malignant transformation of immortalized human bronchial epithelial cells BEP2D induced by alpha particle radiation. METHODS: Western blot was used to detect the expression of autophagy related proteins(LC3B-II, LC3B-I and P62) in alpha particles exposed BEP2D and in exposed malignant transformed cell line BERP35T-1. Intracellular autophagosomes were observed by transmission electron microscopy. BERP35T-1 cells were also treated with 40 and 60 μmol/L autophagy inhibitor chloroquine(CQ) and 25 pmol/L autophagy activator Rapamycin(Rapa), respectively, for detection of of LC3Bs and P62. Survival rates of cells were measured by CCK-8, invasion ability by the Transwell invasion assay, and the migration ability by the scratch healing assay. RESULTS: Compared with BEP2D cells, the numbers of autophagosomes in RH24 and BERP35T-1 cells were increased, LC3B-II/I protein ratio increased, and P62 protein expression decreased. After treatment with 40 and 60 μmol/L CQ for 48 h, the LC3B-II/I protein ratio and the expression level of P62 protein in BERP35T-1 cells were increased, and the cell survival rate, invasion number and scratch closure rate decreased(all P<0.01). After treatment with 25 pmol/L Rapa for48 h, the LC3B-II/I protein ratios were increased, the expression of P62 protein decreased, and the survival rate of BERP35T-1 cells, invasion number and scratch closure rate were increased(P<0.05 or 0.01).CONCLUSION: During the alpha particle-induced malignant transformation of BEP2D cells, autophagy was enhanced which was associated with increased ability of cell proliferation, invasion and migration.
苯并[b]荧蒽和二苯并[a,h]蒽对成年雄性大鼠氧化应激和炎症因子的影响
KANG Zhen, YU Tianyi, LIU Xiaobo, HONG Qianqi, CAI Shurui, YAN Hai
2024, 36(1):  16-20.  doi:10.3969/j.issn.1004-616x.2024.01.003
Abstract ( 146 )   PDF (1119KB) ( 121 )  
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OBJECTIVE: To investigate effects of benzo[b]fluoranthene (BbFA) and dibenzo[a, h]anthracene(Dah A) exposure on oxidative stress and inflammatory factors in rats.METHODS: After 1 week of acclimatization, 48 adult male SD rats were randomly divided into exposed and control groups.The rats were exposed to Bb FA and Dah A by intratracheal instillation twice a week in 4 weeks.Inflammatory factors in BALF and serum, and oxidative stress factors in lung tissue and serum were determined.RESULTS: Serum activity of SOD was significantly decreased in the Dah A-exposed groups (P<0.05).Meanwhile, the Bb FA+Dah A exposed groups showed significantly increased levels of MDA, NO, i-NOS in the lung tissue compared with the control group (P<0.05), and the levels of MDA and i-NOS in the Bb FA+Dah A combined exposure group were significantly higher than that of the Bb FA-exposed and the Dah A-exposed groups (P<0.05).Additionaly, the content of MDA in the Bb FA+Dah A combined exposure group was significantly higher than low dose group of Bb FA-exposed group and Dah A-exposed group (P<0.05).The levels of IL-6 in the Bb FA+Dah A combined exposure group were significantly up-regulated compared with the Bb FA-exposed and the Dah A-exposed groups(P<0.05).CONCLUSION: Our results demonstrated that Bb FA and Dah A caused changes in inflammatory and oxidative factors that were related to inhibition of SOD activity and elevation of i NOS activity, and MDA, NO and IL-6 levels.
基于UPLC-MS/MS方法分析哈萨克族食管鳞癌患者的血清脂质组学特征
LIU Ruixue, LI Desheng, ZHANG Liwei
2024, 36(1):  21-28,34.  doi:10.3969/j.issn.1004-616x.2024.01.004
Abstract ( 146 )   PDF (12290KB) ( 189 )  
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OBJECTIVE: To explore characteristics of lipid metabolism in Xinjiang Kazakh patients with esophageal squamous cell carcinoma(ESCC) based on serum lipidomics. METHODS: From January 2018 to December 2020, 30 Kazakh ESCC patients in the thoracic surgery department of the First Affiliated Hospital of Xinjiang Medical University(ESCC group) and 30 Kazakh healthy people who underwent physical examination in the Health Management Center of Xinjiang Medical University(control group) were selected.Ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS/MS) was used to analyze the targeted quantitative lipidomics of serum in the two groups. Absolute lipid quantification was performed according to relationships between the peak areas and the actual concentrations of internal standard(IS) of similar lipids. Multivariate statistical analyses were performed using the lipid data. RESULTS: A total of 13lipids were screened out in 60 serum samples, among which triacylglycerol(TAG), phosphatidyl choline(PC)and phosphatidyl ethanolamine(PE) were the most abundant. Lysophosphatidylcholine(LPC) was the most different lipid in serum between the two groups. Compared with the control group, the levels of TAG and LPC in the serum of Kazakh ESCC patients were up-regulated, while PE was down-regulated. According to the orthogonal partial least squares-discriminant analysis(OPLS-DA), the threshold(P<0.05 and fold change>2 or <0.5), a total of 77 differential lipid metabolites were screened, among which 34 were up-regulated and 43 were down-regulated in ESCC group compared with control group. Including triglycerides, diglycerides, lysophosphatidyl choline, phosphatidyl ethanolamine and free fatty acids. CONCLUSION: The contents and trends of different lipids in the patients were different. The contents of triglyceride, phosphatidyl choline and ceramide in serum of patients were up-regulated, while the contents of lysatidyl choline and diglyceride were overall down-regulated. The contents of triglyceride and lysophosphatidyl choline in the serum of the Kazakh patients were up-regulated, while phosphatidyl ethanolamine was down-regulated, and the chain length and unsaturation of lysophosphatidyl choline, phosphatidyl ethanolamine and phosphatidyl choline were down-regulated in the serum of patients. Therefore, the analysis of changes in the distribution of these lipids and the screening of new targets are helpful to clarify mecahnisms for occurrence and development of ESCC patients of Xinjiang Kazak nationality.
PGAM5在胰腺癌中的表达及其与临床病理指标的关系
XUE Song, HU Jiahai, DONG Xiangning
2024, 36(1):  29-34.  doi:10.3969/j.issn.1004-616x.2024.01.005
Abstract ( 166 )   PDF (8533KB) ( 263 )  
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OBJECTIVE: To investigate expression levels of phosphoglycerate-mutase 5(PGAM5) in pancreatic cancer tissues and its associations with the clinicopathologic characteristics in the cancers among patients. METHODS: Differences of PGAM5 mRNA expression levels in pancreatic cancer and normal tissues were analyzed using RNA-seq datasets from The Cancer Genome Atlas(TCGA) and Genotype-Tissue Expression(GTEx). Eighty-six patients with pancreatic cancer who attended the First People's Hospital of Chuzhou from January 2018 to December 2020 were selected. Pathological specimens and clinical data of the patients were collected. Concentrations of the PGAM5 protein in the homogenates of 6 fresh pancreatic cancer tissues were detected by Western blot. Expression levels of PGAM5 in 86 pancreatic cancer tissues was detected by immunohistochemistry(IHC). Correlations between these expression levels and clinicopathologic characteristics were determined. Cox regression and Kaplan-Meier curves were used for survival analysis.RESULTS: Bioinformatics analysis showed that the expression levels of PGAM5 mRNA in pancreatic cancer tissues were significantly higher than that in normal tissues(P<0.001). Western blot assay showed that expression levels of the PGAM5 protein were elevated in fresh pancreatic cancer tissues. IHC staining showed that PGAM5 in the cancer tissues was in the form of brownish-yellow granules, and it was mainly expressed in the cytoplasm of cells. Semi-quantitative analysis revealed that the expression levels of PGAM5 were significantly elevated in the cancer tissues compared with paired paracancerous normal tissues(P<0.01). The expression levels of PGAM5 were correlated with TNM stage(P=0.001), tumor length(P=0.006), and distant metastasis(P=0.004) but not with age(P=0.772), gender(P=0.911), or lymph node metastasis(P=0.085).Spearman's correlation analysis showed that PGAM5 was associated with TNM stage(r=0.428, P<0.01), tumor length(r=0.276, P=0.010), lymph node metastasis(r=0.238, P=0.027), and distant metastasis(r=0.304, P=0.004) but not with age(r=0.013, P=0.902) or gender(r=0.042, P=0.699). Univariate analysis suggested that high PGAM5 expression increased the risk of death in pancreatic cancer patients, and the difference was statistically significant [HR=2.548, 95%CI=(1.556, 4.174), P<0.01]. Multifactorial analysis revealed that PGAM5[HR=2.125, 95%CI(1.210, 3.646), P=0.008], lymph node metastasis [HR=5.028, 95%CI(1.776, 14.240)], P=0.002 and distant metastasis [HR=8.866, 95%CI(4.470, 17.584), P<0.01] demonstrated independent influences on the survival prognosis of the patients. Kaplan-Meier survival curves showed that the median overall survival(OS) of the patients in the PGAM5 high expression group was 17 months, and that of the PGAM5 low expression group was 27 months, and the difference was statistically significant [HR=2.470, 95% CI(1.533, 3.980), P<0.01]. CONCLUSION: The expression levels of PGAM5 were elevated in pancreatic cancer tissues and were closely related to the malignant clinicopathologic features of the cancer patients, and the high expression of PGAM5 suggests poor prognosis. PGAM5 may be a potential biomarker for pancreatic cancer.
头孢曲松及其杂质对斑马鱼肝脏的毒性
ZHANG Rui, MA Yuanyuan, HAN Ying, CHONG Xiaomeng, LIU Xinyan, XIE Guangyun, LIANG Yifan, YAO Shangchen, ZHANG Jingpu
2024, 36(1):  35-41,47.  doi:10.3969/j.issn.1004-616x.2024.01.006
Abstract ( 178 )   PDF (43759KB) ( 196 )  
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OBJECTIVE: The objective of this study was to investigate the hepatotoxicity of ceftriaxone and its impurities in zebrafish. METHODS: Wild-type strain zebrafish at 72 h post-fertilization(hpf) and transgenic zebrafish Tg(fabp10a:Ds Red) with liver-specific fluorescence labeling were chosen as experimental animals.Zebrafish larvae were treated with different concentrations of ceftriaxone(at concentrations of 1, 2, 5 mmol/L) and its impurities A, B, C, D and impurities E(at concentrations of 0.1, 0.5, 1 mmol/L) for 2 days. The liver morphology of wild-type zebrafish larvae and the fluorescence intensity of transgenic zebrafish larvae were observed, and the hepatotoxicity of each group was assessed by comparison with the control group. Whole-body Oil Red O staining was employed to observe changes in liver fat content. Additionally, transcriptomic sequencing was performed to detect the gene expression profiles of zebrafish in each treatment group. Differential expression genes were screened(735 differential genes in ceftriaxone group, 237 in impurity A group and 237 in impurity C group), and Gene and Genomes(KEGG) pathway enrichment analysis was conducted. RESULTS: Ceftriaxone and impurities A and C caused an enlargement of the zebrafish liver region or an increase in fluorescence intensity compared to the control group(P<0.05 or 0.01). Impurities B, D, and E primarily resulted in a reduction of the liver region or a decrease in fluorescence intensity compared to the control group(P<0.05 or 0.01). Overall Oil Red O stain assays indicated that both ceftriaxone and its impurities could cause an increase in liver fat. Differential gene expression was observed in each treatment group through transcriptome sequencing.KEGG pathway analysis revealed different pathway enrichments in each group. Genes related to ceftriaxone were mainly enriched in 10 pathways, including metabolism. Genes related to impurity A were mainly enriched in signaling pathways such as tryptophan metabolism. Genes related to impurity C were mainly enriched in signaling pathways, including calcium signaling. CONCLUSION: The study provides insights into the hepatotoxic effects of ceftriaxone and its impurities in zebrafish, demonstrating varied impacts on liver morphology, fluorescence intensity, and gene expression profiles. The findings highlight potential pathways through which these substances may induce hepatotoxicity.
白细胞介素-17A与雌激素受体α和β在上皮性卵巢癌组织中的表达及其临床意义
WANG Kefang, CHEN Yu, WU Chenyu, LIU Mei, WANG Lijie, TIAN Jianguang, ZHOU Xiaohui, XU Lan
2024, 36(1):  42-47.  doi:10.3969/j.issn.1004-616x.2024.01.007
Abstract ( 137 )   PDF (1777KB) ( 149 )  
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OBJECTIVE: To investigate expression levels of interleukin(IL)-17A and estrogen receptor α(ERα) and ERβ in epithelial ovarian cancer(EOC) tissues and their relationship with clinicopathological features and prognosis. METHODS: Clinical and pathological data of 102 EOC patients admitted to Wuxi Maternal and Child Health Hospital during August 2018-August 2022 were retrospectively analyzed. IL-17A, ERα, and ERβ mRNA expressions in cancer tissues and paracellular tissues were detected by real-time fluorescence quantitative PCR(qPCR), and the ERα/β ratio was calculated. The relationships between IL-17A m RNA, ERα/β and clinicopathological features were analyzed. Effects of IL-17A m RNA, ERα/β on the prognostic overall survival of EOC were analyzed by the Kaplan-Meier method and Cox regression analysis.RESULTS: Expressions of IL-17A, ERα and ERα/β were higher in the cancer than the paracancer tissues, while the expression of ERβ was decreased(P<0.05). The high and low expression groups of IL-17A and ERα/βwere divided by the mean values of 0.52 and 3.85, respectively, and the results showed that high IL-17A expression and high ERα/β ratio were associated with FIGO stage, lymph node metastasis, and the amount of ascites(P<0.05). The follow-up period ranged from 12 to 60 months, with a median follow-up period of 36 months, and a total of 38 cases(37.25%) died during the follow-up period. Kaplan Meier analysis showed that the cumulative survival rate of those with high IL-17A mRNA expression was lower than that of those with low expression(P<0.05), and the cumulative survival rate of those with high ERα/β ratio was lower than that of those with low ERα/β ratio(P<0.05). Multifactorial Cox analysis showed that FIGO stage III + IV, postoperative residual foci >2 cm, high expression of IL-17A mRNA, and high ERα/β ratio were independent risk factors for overall survival in patients with EOC(P<0.05). CONCLUSION: IL-17A, ERα and ERα/βwere up-regulated while the ERβ mRNA level was down-regulated in EOC, and the prognosis of EOC patients with high IL-17A expression and high ERα/β ratio was poor.
齐墩果酸对B淋巴细胞损伤的保护作用并基于网络药理学探索其作用机制
DAI Yuxin, LIANG Lichun, PENG Linqian, MENG Fanqi, HAN Xianfeng, ZHANG Yue, YANG Yu, SHANG Yu
2024, 36(1):  48-52.  doi:10.3969/j.issn.1004-616x.2024.01.008
Abstract ( 155 )   PDF (4176KB) ( 144 )  
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OBJECTIVE: This study evaluated the protective effect of oleanolic acid on cyclophosphamide-induced B lymphocyte injury in mice. METHODS: Kunming mice were given cyclophosphamide(80 mg/kg)per day to establish an immunosuppressive animal model. After modeling, oleanolic acid(25 mg/kg) was given per day for 28 days as the interventional group. At the same time, the model group and the blank group were set as controls. The percentage of bone marrow B lymphocyte subsets in each group was detected by flow cytometry. The chemical structure of oleanolic acid was obtained by PubChem database, and the drug target of oleanolic acid was predicted by the Swiss Target Prediction database. Analyses viathe protein interaction network, GO biological process enrichment and KEGG signal pathway enrichment of potential drug targets were carried out by the STRING platform. RESULTS: After administration of cyclophosphamide, the percentage of mature B cell subsets(Ig D and B220 double positive cells) in the model group(2.585%±0.248%) was significantly lower than that in the blank group(8.235%±0.361%), while the percentage in the oleanolic acid interventional group(3.395%±0.445%) was significantly higher than that in the model group(P<0.01). Potential drug targets of oleanolic acid such as PTPN1 and CD81 were screened by the Swiss Target Prediction database. After SRTING platform analysis and Cytoscape remapping calculation, the top 5 node proteins in connectivity were PPARG, PTGS2, PPARA, MAPK3 and HMGCR. From the GO biological process enrichment and KEGG signaling pathway analyses, the pharmacological effects of oleanolic acid were enriched in biological processes such as negative regulation of lipid storage and B cell receptor signaling pathway. CONCLUSION: Oleanolic acid administration to mice increased the percentage of mature B cell subsets in bone marrow and enhanced the development of B lymphocytes by affecting the BCR signaling pathway.
CXCR2在食管癌组织中的表达及其对食管癌细胞生物学行为的影响
HUANG Conggai, LIU Qing, ZHENG Shutao, LIU Tao, TAN Yiyi, PENG Tianyuan, CHEN Jiao, LU Xiaomei
2024, 36(1):  53-57,65.  doi:10.3969/j.issn.1004-616x.2024.01.009
Abstract ( 179 )   PDF (5422KB) ( 264 )  
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OBJECTIVE: To investigate expression of the CXC receptor 2(CXCR2) in esophageal squamous cell carcinoma(ESCC) tissues and its impact on the biological behavior of esophageal cancer cells.METHODS: A total of 74 cases of surgically removed ESCC tissues were collected as the study group and 74 cases of paired adjacent normal esophageal tissues were collected as the control group. CXCR2 expression was detected by immunohistochemical staining, and the difference of CXCR2 expression level between the study and the control groups was compared, and the relationship between CXCR2 expression and clinicopathological characteristics was analyzed. The effects of CXCR2 antagonist SCH527123 on the biological behavior of esophageal cancer cells KYSE30 were examined by CCK-8 cell proliferation, plate colony formation, cell migration and invasion assay. RESULTS: The positive expression rate of CXCR2 in ESCC was 73.0%(54/74), which was significantly higher than the 13.5%(10/74) in the adjacent normal tissues(χ2=53.298, P=0.000). Significant differences were also detected in relation to the differentiation degree and lymph node metastasis of ESCC(χ2=5.515, P=0.019; χ2=7.320, P=0.007). However, the expression was not significantly related to gender, age, tumor location, gross classification of tumor, tumor diameter, depth of invasion, vessel emboli and nerve invasion(P>0.05). In the KYSE30 cells, application of the antagonist SCH527123 significantly inhibited their proliferation, migration, and invasion. CONCLUSION: CXCR2 expression was up regulated in ESCC tissues and was associated with poor prognosis of patients.CXCR2 antagonist SCH527123 inhibited the proliferation, migration, and invasion of esophageal cancer cells in vitro. CXCR2 may therefore be a molecular marker for molecular prediction and targeted therapy of esophageal cancer.
细菌回复突变试验菌株鉴定方法的比较
GAO Mei, TANG Liansheng, ZHENG Zhiyong, MA Hui, QIN Chunxue, CAO Chong
2024, 36(1):  58-65.  doi:10.3969/j.issn.1004-616x.2024.01.010
Abstract ( 232 )   PDF (11541KB) ( 145 )  
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OBJECTIVE: Compare and analyze the identification methods of test strains in bacterial reverse mutation assays(Ames test) for food, medical devices, cosmetics, chemicals, pesticides and drugs in China, in order to provide references for strain identification methods. METHODS: According to the requirements of national and the profession standard, technical standards and guidelines related to Ames tests, the identification methods of histidine auxotrophy, lipopolysaccharide barrier defect(rfa mutation), ampicillin resistance(R factor), tetracycline resistance(pAQ1 plasmid) and uvrB repair deficiency(sensitivity to ultraviolet light) were analyzed and compared. RESULTS: The results showed that TA97a, TA98, TA100, TA102 and TA1535 strains all required histidine for growth, all had rfa mutations, all had ampicillin resistance except TA1535, and all were sensitive to ultraviolet light and all had no tetracycline resistance except TA102.CONCLUSION: Although the identification methods were different, the criteria and identification results were the same. Each laboratory should specify the method and frequency of identification of test strains to provide fundamental guarantee for the authenticity and reliability of Ames test results.