1.Inhibition of gasdermin D-dependent pyroptosis attenuates the progression of silica-induced pulmonary inflammation and fibrosis.
Meiyue SONG ; Jiaxin WANG ; Youliang SUN ; Junling PANG ; Xiaona LI ; Yuan LIU ; Yitian ZHOU ; Peiran YANG ; Tianhui FAN ; Ying LIU ; Zhaoguo LI ; Xianmei QI ; Baicun LI ; Xinri ZHANG ; Jing WANG ; Chen WANG
Acta Pharmaceutica Sinica B 2022;12(3):1213-1224
Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide, but the molecular basis underlying its development remains unclear. An accumulating body of evidence supports gasdermin D (GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases. However, there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis. In this work, we investigated the role of GSDMD-mediated pyroptosis in silicosis. Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression. Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica. Measurement of interleukin-1β release, lactic dehydrogenase activity, and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages. Additionally, we verified that both canonical (caspase-1-mediated) and non-canonical (caspase-4/5/11-mediated) signaling pathways mediated silica-induced pyroptosis activation, in vivo and in vitro. Notably, Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes, which highlighted the pivotal role of pyroptosis in this disease. Taken together, our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis.
2.Investigation of contamination of SARS-CoV-2 in imported frozen seafood from a foreign cargo ship and risk factors for infection in stevedores in Qingdao
Jing JIA ; Qun YUAN ; Jianwen HUI ; Jiwei LIANG ; Xia WANG ; Huihui LIU ; Zhaoguo WANG ; Xiaoqi DAI ; Bi HAO ; Ruqin GAO ; Fachun JIANG ; Huilai MA
Chinese Journal of Epidemiology 2021;42(8):1360-1364
Objective:To investigate the contamination status of SARS-CoV-2 in imported frozen seafood from a Russia cargo ship in Qingdao and to analyze the risk factors for infection in local stevedores.Methods:The method of "two-stage, full coverage and mixed sampling" was used to collect the seafood packaging samples for the nucleic acid detection of SARS-CoV-2 by real-time fluorescent quantitative RT-PCR. A unified questionnaire was designed to investigate 71 stevedores in two shifts through telephone interview. The stevedores were divided into two groups, with 23 in the shit with two infections was group A and 48 in the shift without infection was group B. Software Epi Info7.2 was used to identify the risk factors for SARS-CoV-2 infections in the stevedores.Results:In the frozen seafood from a Russia cargo ship, the total positive rate of SARS-CoV-2 nucleic acid in the frozen seafood was 11.53% (106/919). The positive rate of SARS-CoV-2 nucleic acid in the frozen seafood unloaded by group A (14.29%,70/490) was significantly higher than that in the frozen seafood unloaded by group B (8.39%,36/429)( χ2=7.79, P=0.01) and the viral loads detected in the frozen seafood unloaded by group A were higher than those detected in the frozen seafood unloaded by group B. The scores of personal protection and behaviors in the stevedores in group A were significantly lower than those in group B ( P<0.05), and toilet use, smoking and improper hand washing before meals were the risk factors for the infection. Conclusions:The imported frozen seafood was contaminated by SARS-CoV-2 and the contamination distribution was uneven. Supervision and management of personal occupational protection and behaviors of workers engaged in imported frozen food transportation should be strengthened. It is suggested that a closed-loop monitoring and management system for the whole process of "fishing-transport- loading/unloading" should be established by marine fishery authority.
3. Application of closed negative pressure drainage technique in repair of wound of hand trauma infection
Xiaoyan XIONG ; Zhaoguo ZHANG ; Chao LIU ; Xiqing CHENG
Chinese Journal of Primary Medicine and Pharmacy 2019;26(9):1042-1045
Objective:
To explore the application value of closed negative pressure drainage technique in wound healing of hand trauma.
Methods:
From August 2013 to October 2017, 80 patients with hand trauma in the Traditional Chinese Medicine Hospital of Cixi were divided into two groups according to the random principle, with 40 cases in each group.The control group was treated with conventional wound repair, and the observation group was treated with closed negative pressure drainage.The repair effect, healing, secondary operation, antibiotic use, hospitalization, histopathological score and patients' satisfaction were observed.
Results:
The total effective rate of the observation group (97.50%) was obviously higher than that of the control group(80.00%)(χ2=6.13,
4.Role of ADAM8 in tumor metastasis
Qi JIA ; Zhaoguo LIU ; Suyun YU ; Lichuan CHEN ; Pingting ZHU ; Wenxing CHEN ; Aiyun WANG ; Yin LU
Chinese Pharmacological Bulletin 2017;33(8):1037-1040
Tumor metastasis is one of the important biological characteristics of malignant tumor,which is closely related with the prognosis of the cancer patients.High expression of ADAM8 in varieties of tumors was revealed in many recent studies,and such aberrant expression played a crucial role in regulating of tumor metastasis.Studies showed that overexpression of ADAM8 attenuated the intercellular adhesion effect,promoted tumor angiogenesis,and enhanced the degradation of ECM as well as the releasing of cytokines.Therefore,suppression of ADAM8 may lead to inhibition of tumor metastasis,which makes ADAM8 a particular attractive target as it can be used as a prognostic indicator and a potential therapeutic target of malignant tumor.A review about the relations between ADAM8 protein′s abnormal expression and tumor occurrence was discussed in this paper,also include discussion about the mechanisms of ADAM8 protein′s disorder-induced tumor formation,as well as therapeutic strategies based on ADAM8-targeted,which may provide references for follow-up research and clinical treatment.
5.Downregulated Hsa-let-7f contributes to the loss of type II collagen by targeting interleukin-10/STAT3 signaling pathway in degenerative lumbar scoliosis
Lei WANG ; Tianwang LI ; Jianqiang LIU ; Xiaozong LIU ; Zhaoguo WANG ; Yan TIAN ; Yongxing ZHANG ; Wei WANG
Chinese Journal of Tissue Engineering Research 2016;20(15):2225-2232
BACKGROUND:MicroRNAs (miRNAs) play an important role in a variety of diseases. Investigation of miRNA expression profile in degenerative lumbar scoliosis is beneficial for understanding its pathogenesis, providing a novel therapeutic target. Therefore, we tested the hypothesis that miRNAs promote intervertebral disc degeneration through the interleukin-10/STAT3 signaling pathway, a potential regulator of intervertebral disc degeneration.
OBJECTIVE:To compare the differentialy expressed miRNAs in the intervertebral disc tissues from patients with degenerative lumbar scoliosis and normal controls and to identify specific miRNAs in degenerative lumbar scoliosis folowed by functional validation.
METHODS: An initial screening of miRNA expression in nucleus pulposus tissues by miRNA Solexa Sequencing was performed in samples from 10 patients with degenerative lumbar scoliosis and 10 controls, respectively. Subsequently, differentialy expressed miRNAs were validated using qRT-PCR. The level of differentialy expressed miRNAs in degenerative nucleus pulposus tissues was investigated. Then, functional analysis of the miRNAs in regulating type II colagen expression was carried out. Western blot and luciferase reporter assay were used to further confirm the target gene.
RESULTS AND CONCLUSION: We identified 30 miRNAs that were differentialy expressed (16 upregulated and 14 downregulated) in patients with degenerative lumbar scoliosis compared with controls. Folowing qRT-PCR confirmation, Has-let-7f was significantly down-regulated in degenerative nucleus pulposus tissues as compared with controls. Moreover, its level was correlated with the severity of disc degeneration. Overexpression of Has-let-7f promoted type II colagen expression in nucleus pulposus cels. Knockout of interleukin-10 induced effects on nucleus pulposus cels similar to Has-let-7f. Bioinformatics target prediction identified interleukin-10 as a putative target of Has-let-7f. Furthermore, luciferase reporter assays demonstrated that Has-let-7f altered the expression of STAT3 and matrix metaloproteinase-2. These findings indicate that the downregulation of Has-let-7f induces type II colagen loss by directly targeting inleukin-10, thereby resulting in intervertebral disc degeneration and degenerative lumbar scoliosis. Has-let-7f is likely to be a novel therapeutic target for degenerative lumbar scoliosis.
6.MicroRNA-491-5p is involved in the pathogenesis of degenerative lumbar scoliosis by targeting matrix metalloproteinase 9
Lei WANG ; Tianwang LI ; Jianqiang LIU ; Xiaozong LIU ; Zhaoguo WANG ; Yan TIAN ; Yongxing ZHANG ; Wei WANG
Chinese Journal of Tissue Engineering Research 2016;(2):248-253
BACKGROUND:MicroRNAs are widely involved in the regulation of protein expression, and play a critical role in many physiological and pathological processes in the body. But microRNA expression profile in degenerative lumbar scoliosis is rarely reported and understood. OBJECTIVE:To compare the microRNA expression profile in the normal intervertebral disc and degenerative lumbar scoliosis and to identify degenerative lumbar scoliosis-specific microRNAs, folowed by functional validation. METHODS: Total RNA samples were extracted from the nucleus pulposus tissues of 57 patients with degenerative lumbar scoliosis as experimental groups and the normal nucleus pulposus tissues of 42 patients with lumbar fractures as control group. An initial screening of differentialy expressed microRNAs in the nucleus pulposus tissues by microRNA microarray was performed in 10 samples from each group. Subsequently, differentialy expressed microRNAs were validated using real-time quantitative RCR. The level of differentialy expressed microRNAs in the degenerative nucleus pulposus tissues was investigated. Then, the functional analysis of microRNAs in regulating colagen II expression was carried out. Western blot and luciferase reporter assay were also used to detect target genes. RESULTS AND CONCLUSION:We identified 22 microRNAs that were differentialy expressed (17 upregulated and 5 downregulated) in degenerative lumbar scoliosis patients compared with the controls. Folowing real-time quantitative RCR confirmation, miR-491-5p was significantly down-regulated in degenerative nucleus pulposus tissues in comparison with the controls. Moreover, its level was closely correlated with the pathological grading of disc degeneration. Overexpression of miR-491-5p promoted type II colagen expression in nucleus pulposus cels. Bioinformatics target prediction identified matrix metaloproteinase-9 as a putative target of miR-491-5p. Furthermore, luciferase reporter assays demonstrated that miR-491-5p directly targeted matrix metaloproteinase-9 and affected its protein expression in nucleus pulposus cels. These results show that the downregulation of miR-491-5p induces type II colagen loss by directly targeting matrix metaloproteinase-9, thereby resulting in degeneration of the intervertebral disc and degenerative lumbar scoliosis. This study also underscores the potential of miR-491-5p as a novel therapeutic target in degenerative lumbar scoliosis.
7.Research progress on relationship between glucose transporter 1 and tumor energy metabolism
Suyun YU ; Zhaoguo LIU ; Qi JIA ; Lichuan CHEN ; Pingting ZHU ; Wenxing CHEN ; Aiyun WANG ; Yin LU
Chinese Pharmacological Bulletin 2016;32(7):906-909
The study on tumor metabolism has been gradually be-come a hot spot in recent years .A lot of proteins involved in the regulation of tumor metabolism especially the glucose transporter protein 1(GLUT1).As a key regulatory factor mediating energy metabolism within tumor cells , GLUT1 can regulate the glucose intake and maintain the basic level of metabolism in tumor cells . More importantly, the abnormal expression of GLUT1 was asso-ciated with many kinds of tumors , of which GLUT1 was used to meet the energy requirement for the fast growth of tumor .Thus GLUT1 also played a crucial role in growth , differentiation and metastasis of tumor cells and prognosis of tumors .Meanwhile , as three-dimensional crystal structure of GLUT 1 was determined , it is possible to design the small molecular inhibitors of GLUT 1, which can realize “starve to death” tumor cells.GLUT1 can be a particularly attractive target for tumor treatment and interfer-ence.The relationship between abnormal expression of GLUT 1 protein and tumor metabolism was reviewed . Moreover , the mechanism of tumor metabolism regulated by GLUT 1 protein ex-pression and treatment of cancers were discussed , which may provide references for future research and clinical treatment .
8.Research progress of a new oncotherapy target TRAP1
Peiliang SHEN ; Zhaoguo LIU ; Lihua SUN ; Xu WANG ; Ying SHEN ; Hongyan WU ; Aiyun WANG ; Yin LU
Chinese Pharmacological Bulletin 2016;32(4):459-462,463
Tumor necrosis factor receptor-associated protein 1 (TRAP1),as one of the main members of the heat shock protein 90 family, resists oxidative stress-induced apoptosis as well as predominantly maintains the integrity of mitochondria and cellu-lar homeostasis. Abnormal expression of TRAP1 was herein closely related to the onset and progression of a wide variety of tumors. As a key regulatory factor mediating energy metabolism within tumor cells, TRAP1 may be able to kill them by interfer-ing with such metabolism. More importantly, the abnormal ex-pression of TRAP1 played a less important role in normal cells, allowing TRAP1 to be a particularly attractive target as it can be used in tumor treatment or interference. The relationship be-tween abnormal expression of TRAP1 protein and tumor onset was reviewed. Besides, the mechanism by which disordered TRAP1 protein expression induced tumor formation was postula-ted, which may provide references for future research and clini-cal treatment.
9.Effects of the total flavonoids of scutellaria barbataon on atherosclerosis and expression of PLTP in ApoE gene deficiency mice
Pingting ZHU ; Yun SUN ; Zhaoguo LIU ; Yuping LIU ; Ping BU
Chinese Pharmacological Bulletin 2015;(6):833-837,838
Aim To observe the effects of the total fla-vonoids of scutellaria barbataon ( TFSB ) on high-fat
feeding ApoE gene deficiency mice in early atheroscle-rosis ( AS ) and its underlying mechanisms. Methods
40 ApoE-/ -male mice were divided into five groups:model group, SIM group and L-TFSB, M-TFSB, H-TFSB group, 5 C57BL/6J mice were selected as nor-mal control group. All mice in experimental group were fed with high-lipid diet for 4 weeks and all mice were killed after 8 weeks. H&E staining was used to observe morphology of aorta. Blood rheometer was used to ex-amine plasm viscosity and whole blood viscosity. Fully automatic biochemical analyser was used to detect the serum levels of TG, TC, LDL-C and HDL-C. The ex-pression levels of PLTP and VE in serum were meas-ured by ELISA. The expression levels of PLTP and FXR in liver were examined by Western blot. Results The model was established successfully. TFSB groups could improve the aorta AS morphology of model mice and significantly reduce the serum levels of TG, TC and LDL-C, while increase the level of HDL-C ( P<0. 05 or P<0. 01 ) . TFSB groups could decrease the
hematocrit value, plasma viscosity and whole blood vis-cosity of AS model mice significantly and had statistical significance when compared with model group ( P <0. 01 ) . The expression levels of PLTP of serum were reduced significantly when compared with model group ( P <0. 01 ) . We also found that the expression of PLTP was in negative correlation with VE ( r = -0. 675,P<0. 01). M-TFSB and H-TFSB group could decrease the expressions of PLTP and FXR of liver when compared with model group ( P <0. 01 ) . Con-clusion TFSB may exert its anti-AS effect partly through inhibiting the levels of FXR and PLTP of ApoE-/ -mice, increasing the level of VE, regulating blood lipids, improving blood rheology and reducing the damage of AS in mice.
10.Research progress of salvianolic acid B in cardiovascular diseases
Chao LIN ; Zhaoguo LIU ; Xing QIAN ; Yuan YAO ; Bin XU ; Huimin BIAN
Chinese Pharmacological Bulletin 2015;(4):449-451,452
Cardiovascular disease is a serious threat to human health and quality of life ,and it has become the leading cause of death in human.Thus,looking for effective drugs to reduce the mortality and morbidity of such a disease has become a problem to be solved.Due to its good efficacy of activating blood circula-tion and dissipating blood stasis,salvia miltiorrhiza has been widely used in the treatment of cardiovascular disease and ob-tained a good curative effect.Salvianolic acid B is one of the main water-soluble components of salvia miltiorrhiza extract and studies have shown that salvianolic acid B possesses many biolog-ical activities,which not only has a good protective effect on my-ocardial infarction,but could significantly alleviate myocardial ischemia-reperfusion injury.This article reviews the research progress of salvianolic acid B in cardiovascular diseases,and al-so includes discussion about the mechanisms of salvianolic acid B in the regulation of cardiovascular diseases,which may provide references for follow-up research and clinical treatment.

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