Publications by authors named "Shuqing Liu"

106 Publications

Matrine treatment reduces retinal ganglion cell apoptosis in experimental optic neuritis.

Sci Rep 2021 May 4;11(1):9520. Epub 2021 May 4.

Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Inflammatory demyelination and axonal injury of the optic nerve are hallmarks of optic neuritis (ON), which often occurs in multiple sclerosis and is a major cause of visual disturbance in young adults. Although a high dose of corticosteroids can promote visual recovery, it cannot prevent permanent neuronal damage. Novel and effective therapies are thus required. Given the recently defined capacity of matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, in immunomodulation and neuroprotection, we tested in this study the effect of matrine on rats with experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. MAT administration, started at disease onset, significantly suppressed optic nerve infiltration and demyelination, with reduced numbers of Iba1 macrophages/microglia and CD4 T cells, compared to those from vehicle-treated rats. Increased expression of neurofilaments, an axon marker, reduced numbers of apoptosis in retinal ganglion cells (RGCs). Moreover, MAT treatment promoted Akt phosphorylation and shifted the Bcl-2/Bax ratio back towards an antiapoptotic one, which could be a mechanism for its therapeutic effect in the ON model. Taken as a whole, our results demonstrate that MAT attenuated inflammation, demyelination and axonal loss in the optic nerve, and protected RGCs from inflammation-induced cell death. MAT may therefore have potential as a novel treatment for this disease that may result in blindness.
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http://dx.doi.org/10.1038/s41598-021-89086-7DOI Listing
May 2021

The potential role of miR-124-3p in tumorigenesis and other related diseases.

Mol Biol Rep 2021 Apr 20. Epub 2021 Apr 20.

Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA, 01610, USA.

MicroRNAs (miRNAs) are a class of single-stranded noncoding and endogenous RNA molecules with a length of 18-25 nucleotides. Previous work has shown that miR-124-3p leads to malignant progression of cancer including cell apoptosis, migration, invasion, drug resistance, and also recovers neural function, affects adipogenic differentiation, facilitates wound healing through control of various target genes. miR-124-3p has been mainly previously characterized as a tumor suppressor regulating tumorigenesis and progression in several cancers, such as hepatocellular carcinoma (HCC), gastric cancer (GC), bladder cancer, ovarian cancer (OC), and leukemia, as a tumor promotor in breast cancer (BC), and it has been also widely studied in a variety of neurological diseases, like Parkinson's disease (PD), dementia and Alzheimer's disease (AD), and cardiovascular diseases, ulcerative colitis (UC), acute respiratory distress syndrome (ARDS). To lay the groundwork for future therapeutic strategies, in this review we mainly focus on the most recent years of literature on the functions of miR-124-3p in related major cancers, as well as its downstream target genes. Although current work as yet provides an incomplete picture, miR-124-3p is still worthy of more attention as a practical and effective clinical biomarker.
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http://dx.doi.org/10.1007/s11033-021-06347-4DOI Listing
April 2021

Effect of Musk Tongxin Dropping Pill on Myocardial Remodeling and Microcirculation Dysfunction in Diabetic Cardiomyopathy.

Evid Based Complement Alternat Med 2021 18;2021:6620564. Epub 2021 Mar 18.

Department of Cardiology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, Zhejiang 312000, China.

Objective: To explore the effect of Musk Tongxin Dropping Pill (MTDP) on myocardial remodeling and microcirculation dysfunction in diabetic cardiomyopathy (DCM).

Methods: Forty male SD rats were randomly divided into control group (control group,  = 10), DCM model group (DCM group,  = 10), DCM model + pioglitazone group (DCM + PLZ group,  = 10), and DCM model + MTDP group (DCM + MTDP group,  = 10). An intraperitoneal single injection of 65 mg/kg streptozotocin (STZ) was used to establish rat model of DCM and the rats in control group were treated with the same dose of sodium citrate buffer solution. DCM + PLZ group was treated with 3 mg/kg/d PLZ by ig after modeling, DCM + MTDP group was treated with 22 mg/kg/d MTDP by ig, and DCM group was treated with 2 ml/kg/d sodium carboxymethyl cellulose (CMC-Na) by ig. The general condition of rats was continuously observed. After intervening for 3 weeks, the random blood glucose of rats was detected by tail vein, and the echocardiography examination was performed. Blood specimens were collected from the abdominal aorta, serum nitric oxide (NO) and endothelin-1 (ET-1) were detected to estimate endothelial function, and tumor necrosis factor (TNF-), interleukin 6 (IL-6), IL-1, malondialdehyde (MDA), and superoxide dismutase (SOD) were detected to observe the changes of inflammation and oxidative stress indexes. The heart mass index (HMI) was calculated through the ratio of heart mass (HM) to the corresponding body mass (BM). Myocardial pathological tissue staining was performed.

Results: Compared with control group, blood glucose in other three groups was higher. Left ventricular end systolic diameter (LVSD) and left ventricular end diastolic diameter (LVDD) in DCM group showed a significant increase, while left ventricular ejection fraction (LVEF) and heart rate (HR) in this group displayed an obvious decrease ( < 0.01). BM and HM in DCM group exhibited a reduction, and HM/BM × 10 revealed an apparent increase ( < 0.01). The levels of serum NO and SOD were distinctly downregulated ( < 0.01), and the levels of ET-1, MDA, TNF-, IL-1, and IL-6 were remarkably upregulated ( < 0.01). Compared with DCM group, a significant decrease was observed in LVSD and LVDD in DCM + MTDP group, while LVEF and HR obviously increased ( < 0.05). BM and HM indicated an apparent increase, but HM/BM ×10 reduced distinctly ( < 0.01). The levels of serum NO and SOD were markedly upregulated ( < 0.05), and the levels of ET-1, MDA, TNF-, IL-1, and IL-6 were significantly downregulated ( < 0.05). HE staining showed that myocardial cells arranged neatly in the control group but not in the DCM group. The intercellular space between myocardial cells in DCM group increased, accompanied by damage of myocardial fibers and infiltration of inflammatory cells. Masson staining displayed an increase in interstitial collagen fibers in DCM group. Carstairs staining showed that microembolization occurred in the myocardium in DCM group, while in DCM + MTDP and DCM + PLZ groups the corresponding myocardial pathological changes were significantly improved.

Conclusions: MTDP might show a positive effect on myocardial remodeling and microcirculation dysfunction in DCM rats.
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http://dx.doi.org/10.1155/2021/6620564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997770PMC
March 2021

CRKL promotes hepatocarcinoma through enhancing glucose metabolism of cancer cells via activating PI3K/Akt.

J Cell Mol Med 2021 Mar 1;25(5):2714-2724. Epub 2021 Feb 1.

Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.

Abnormal glucose metabolism may contribute to cancer progression. As a member of the CRK (v-crk sarcoma virus CT10 oncogene homologue) adapter protein family, CRKL (CRK-like) associated with the development and progression of various tumours. However, the exact role and underlying mechanism of CRKL on energy metabolism remain unknown. In this study, we investigated the effect of CRKL on glucose metabolism of hepatocarcinoma cells. CRKL and PI3K were found to be overexpressed in both hepatocarcinoma cells and tissues; meanwhile, CRKL up-regulation was positively correlated with PI3K up-regulation. Functional investigations revealed that CRKL overexpression promoted glucose uptake, lactate production and glycogen synthesis of hepatocarcinoma cells by up-regulating glucose transporters 1 (GLUT1), hexokinase II (HKII) expression and down-regulating glycogen synthase kinase 3β (GSK3β) expression. Mechanistically, CRKL promoted glucose metabolism of hepatocarcinoma cells via enhancing the CRKL-PI3K/Akt-GLUT1/HKII-glucose uptake, CRKL-PI3K/Akt-HKII-glucose-lactate production and CRKL-PI3K/Akt-Gsk3β-glycogen synthesis. We demonstrate CRKL facilitates HCC malignancy via enhancing glucose uptake, lactate production and glycogen synthesis through PI3K/Akt pathway. It provides interesting fundamental clues to CRKL-related carcinogenesis through glucose metabolism and offers novel therapeutic strategies for hepatocarcinoma.
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http://dx.doi.org/10.1111/jcmm.16303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933966PMC
March 2021

Taurine improves neuron injuries and cognitive impairment in a mouse Parkinson's disease model through inhibition of microglial activation.

Neurotoxicology 2021 03 12;83:129-136. Epub 2021 Jan 12.

Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China. Electronic address:

Clinical and experimental findings support the view that activation of hippocampus microglia through NADPH oxidase contributes to cognitive impairment in Parkinson's disease (PD). Taurine, an antioxidant, displays an exclusive physical property on brain function, such as learning and memory. To date, the role of taurine in improving cognitive impairment in PD is not fully uncovered. Hence, we evaluated the protective effect of taurine on cognitive ability and explored the related mechanism in the model built by paraquat and maneb (P + M)-induced PD mice. Then the ability of learning and memory was observed by Morris water maze, neuron loss was evaluated by immunohistochemistry in hippocampus, the level of postsynaptic density 95 (PSD95) and microglia activation was assessed by immunostaining, the molecules (gp91, p47, mac1, p-Src/Src and p-Erk/Erk) were examined by western blot. The results showed that taurine could alleviate the impairments in learning and memory induced by P + M injection in mice (decreased escape latency on day 4, P < 0.01; decreased swimming distance on day 4, P < 0.05; increased percent time in target quadrant, P < 0.05), corresponding with activation of microglia (decreased IBa-1 density, P < 0.001; decreased the protein expression of p47, P < 0.05; decreased protein expression of gp91, P < 0.01; decreased p-Src/Src, P < 0.01; decreased p-Erk/Erk, P < 0.01; decreased mac 1, P < 0.01), decreased neuron loss (increased number of NeurN neuron, P < 0.001; increased protein expression of NeruN, P < 0.01; decreased protein expression of caspase 3, P < 0.01) and increased PSD95 level in hippocampus (P < 0.01). The results indicated that mac1 and Src-Erk signaling was involved in increased NADPH oxidase expression in hippocampus microglia of P + M mice, and taurine could improve injuries in learning and memory through mac1 reduction. The new findings in mac1 triggering hippocampal microglia NADPH oxidase through Src/Erk pathway of the present study might provide a therapy target for PD.
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http://dx.doi.org/10.1016/j.neuro.2021.01.002DOI Listing
March 2021

miR-124-3p Suppresses the Invasiveness and Metastasis of Hepatocarcinoma Cells Targeting CRKL.

Front Mol Biosci 2020 15;7:223. Epub 2020 Sep 15.

Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.

Abnormal expressions of microRNAs are involved in growth and progression of human cancers including hepatocellular carcinoma (HCC). An adaptor protein CRKL plays a pivotal role in HCC growth, whereas miR-124-3p downregulation is associated with clinical stage and the poor survival of patients. However, the relationship between miR-124-3p and CRKL and the molecular mechanisms through which they regulate HCC metastasis remains unclear. In the current work, we explored miR-124-3p and its correlation with CRKL expression in HCC patient tissues. We found that miR-124-3p deficiency is inversely co-related with CRKL overexpression in tumorous tissues of HCC patients, which was also consistent in HCCLM3 and Huh7 HCC cell lines. Target validation data shows that miR-124-3p directly targets CRKL. The overexpression of miR-124-3p reverses the CRKL expression at both mRNA and protein levels and inhibits the cell development, migration, and invasion. Mechanistic investigations showed that CRKL downregulation suppresses the ERK pathway and EMT process, and concomitant decrease in invasion and metastasis of HCC cells. The expressions of key molecules in the ERK pathway such as RAF, MEK, ERK1/2, and pERK1/2 and key promoters of EMT such as -cadherin and vimentin were downregulated, whereas -cadherin, a key suppression indicator of EMT, was upregulated. MiR-124-3p-mediated CRKL suppression led to BAX/BCL-2 increase and C-JUN downregulation, which inhibited the cell proliferation and promoted the apoptosis in HCC cells. Collectively, our data illustrates that miR-124-3p acts as an important tumor-suppressive miRNA to suppress HCC carcinogenesis through targeting CRKL. The miR-124-3p-CRKL axial regulated pathway may offer valuable indications for cancer research, diagnosis, and treatment.
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http://dx.doi.org/10.3389/fmolb.2020.00223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522612PMC
September 2020

Eye Movements of Spatial Working Memory Encoding in Children with and without Autism: Chunking Processing and Reference Preference.

Autism Res 2020 Sep 22. Epub 2020 Sep 22.

College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China.

Individuals with autism spectrum disorder (ASD) experience spatial working memory deficits and show different encoding mechanisms from typical developing (TD) peers. To effectively describe the encoding strategies of those with ASD and highlight their characteristics in cognitive processing, we adopted improved change detection tasks and added eye-movement indicators to investigate the chunking function and reference preference of children with and without ASD. The current study included 20 participants with ASD aged 8-16 and 20 TD children matched for age, gender, and intelligence. Experiment 1 used high/low-structured change detection tasks, and eye-movement indexes were recorded as they memorized the locations of the items to investigate spatial chunking strategies. In Experiment 2, changes in eye movement patterns were observed by adding a frame of reference. The results suggested different encoding strategies in ASD and TD individuals. The ASD group showed local processing bias and had difficulty adopting chunking strategies in spatial working memory. Eye-movement analysis suggested that they rarely showed integrated information processing tendency observed in TD children. Moreover, as a compensatory processing, they were more likely to use the frame of reference. In this study, we compared the spatial chunking strategies and reference preference of children with and without ASD, and eye-movement analysis was used to investigate the processing mechanism. These findings are significant for research on cognitive characteristics of ASD and provide a new focus for working memory training in children with ASD. LAY SUMMARY: The current study suggests that children with autism spectrum disorder are poorer at organizing items into chunks in spatial working memory, but rely more on reference frames. If the purpose of location memory is to strengthen the adaptability of children with autism, it should provide them with more clues or references. If it is for the purpose of intervention such as cognitive training, it should guide them to integrate information to improve the basic cognitive processing efficiency.
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http://dx.doi.org/10.1002/aur.2398DOI Listing
September 2020

miR-429-CRKL axis regulates clear cell renal cell carcinoma malignant progression through SOS1/MEK/ERK/MMP2/MMP9 pathway.

Biomed Pharmacother 2020 Jul 12;127:110215. Epub 2020 May 12.

Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China. Electronic address:

The pathogenesis and tumorigenesis of clear cell renal cell carcinoma (ccRCC) remain unclear. The deregulations of miR-429, a member of miR-200 family, and v-crk sarcoma virus CT10 oncogene homologue (avian)-like (CRKL), an adaptor protein of CRK family, are involved in the development, metastasis and prognosis of various cancers. Current study aimed to demonstrate the differential expressions of miR-429 and CRKL with their correlationship and molecular regulation mechanism in ccRCC malignancy. miR-429 and CRKL separately showed suppressing and promoting effects in ccRCC. Lower miR-429 expression and higher CRKL expression were negatively correlated in surgical cancerous tissues by promoting the advance of ccRCC. By binding to the 3'-UTR of CRKL, miR-429 reversely regulated CRKL for its functionalities in ccRCC cells. CRKL knockdown and overexpression separately decreased and increased the in vitro migration and invasion of 786-O cells, which were consistent with the influences of miR-429 overexpression and knockdown on 786-O through respectively downregulating and upregulating CRKL via SOS1/MEK/ERK/MMP2/MMP9 pathway. The enhancements of CRKL expression, migration and invasion abilities and SOS1/MEK/ ERK/MMP2/MMP9 activation induced by TGF-β stimulation in 786-O cells could be antagonized by miR-429 overexpression. Exogenous re-expression of CRKL abrogated miR-429 suppression on the migration and invasion of 786-O cells. Collectively, miR-429 deficiency negatively correlated with CRKL overexpression promoted the aggressiveness of cancer cells and advanced the clinical progression of ccRCC patients. miR-429-CRKL axial regulation provides new clues to the fundamental research, diagnosis and treatment of ccRCC.
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http://dx.doi.org/10.1016/j.biopha.2020.110215DOI Listing
July 2020

GRIM-19 deficiency promotes clear cell renal cell carcinoma progression and is associated with high TNM stage and Fuhrman grade.

Oncol Lett 2020 Jun 31;19(6):4115-4121. Epub 2020 Mar 31.

College of Basic Medicinal Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.

Clear cell renal cell carcinoma (ccRCC) exhibits the highest mortality among all urological malignancies. The investigation of the potential disease progression markers can improve ccRCC diagnosis and treatment. Gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) is involved in carcinogenesis and cancer progression in a variety of cancer types including RCC. While, its role in ccRCC remains unclear, this cancer type is considered the most aggressive RCC subtype. In the present study, RT-qPCR, western blotting and immunohistochemical (IHC) assays demonstrated that GRIM-19 protein and mRNA levels were downregulated in ccRCC tumor tissues compared with the corresponding levels noted in paracancerous non-tumor tissues. The deficiency of this protein contributed in relaxed and/or collapsed structures of the kidney tubules and collecting duct noted in tumor tissues. Moreover, the reduction in GRIM-19 expression was associated with high tumor, lymph nodes and metastasis (TNM) stage and Fuhrman grade of ccRCC tumors. The data suggested that GRIM-19 acted as a tumor suppressor and that its deficiency promoted ccRCC development and progression. GRIM-19 can be considered a potential tumor marker for ccRCC.
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http://dx.doi.org/10.3892/ol.2020.11498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202299PMC
June 2020

Erratum to: Smad4 mediates malignant behaviors of human ovarian carcinoma cell through the effect on expressions of E-cadherin, plasminogen activator inhibitor-1 and VEGF.

BMB Rep 2020 04;53(4):240

Key Laboratory for Proteomics of Liaoning Province, Dalian Medical University, Dalian University, Dalian 116044, China.

[Erratum to: BMB Reports 2010; 43(8): 554-560, PMID: 20797318] The authors apologize that due to our neglect when doing the picture layout of Fig. 1A, the wrong Western blot analysis image were pasted for the "β-actin"group in the middle plot of Fig. 1A. The middle plot of Fig. 1A and its related statistics results (bottom plot in Fig.1A) have been corrected. However, the conclusions of the original article are not affected. The authors would like to apologize for any inconvenience caused.
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April 2020

Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis.

J Infect 2020 08 23;81(2):e16-e25. Epub 2020 Apr 23.

Department of Cardiology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing City, Zhejiang Province, 312000, PR China. Electronic address:

Background: An epidemic of Coronavirus Disease 2019 (COVID-19) began in December 2019 and triggered a Public Health Emergency of International Concern (PHEIC). We aimed to find risk factors for the progression of COVID-19 to help reducing the risk of critical illness and death for clinical help.

Methods: The data of COVID-19 patients until March 20, 2020 were retrieved from four databases. We statistically analyzed the risk factors of critical/mortal and non-critical COVID-19 patients with meta-analysis.

Results: Thirteen studies were included in Meta-analysis, including a total number of 3027 patients with SARS-CoV-2 infection. Male, older than 65, and smoking were risk factors for disease progression in patients with COVID-19 (male: OR = 1.76, 95% CI (1.41, 2.18), P < 0.00001; age over 65 years old: OR =6.06, 95% CI(3.98, 9.22), P < 0.00001; current smoking: OR =2.51, 95% CI(1.39, 3.32), P = 0.0006). The proportion of underlying diseases such as hypertension, diabetes, cardiovascular disease, and respiratory disease were statistically significant higher in critical/mortal patients compared to the non-critical patients (diabetes: OR=3.68, 95% CI (2.68, 5.03), P < 0.00001; hypertension: OR = 2.72, 95% CI (1.60,4.64), P = 0.0002; cardiovascular disease: OR = 5.19, 95% CI(3.25, 8.29), P < 0.00001; respiratory disease: OR = 5.15, 95% CI(2.51, 10.57), P < 0.00001). Clinical manifestations such as fever, shortness of breath or dyspnea were associated with the progression of disease [fever: 0R = 0.56, 95% CI (0.38, 0.82), P = 0.003;shortness of breath or dyspnea: 0R=4.16, 95% CI (3.13, 5.53), P < 0.00001]. Laboratory examination such as aspartate amino transferase(AST) > 40U/L, creatinine(Cr) ≥ 133mol/L, hypersensitive cardiac troponin I(hs-cTnI) > 28pg/mL, procalcitonin(PCT) > 0.5ng/mL, lactatede hydrogenase(LDH) > 245U/L, and D-dimer > 0.5mg/L predicted the deterioration of disease while white blood cells(WBC)<4 × 10/L meant a better clinical status[AST > 40U/L:OR=4.00, 95% CI (2.46, 6.52), P < 0.00001; Cr ≥ 133μmol/L: OR = 5.30, 95% CI (2.19, 12.83), P = 0.0002; hs-cTnI > 28 pg/mL: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001; PCT > 0.5 ng/mL: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001;LDH > 245U/L: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001; D-dimer > 0.5mg/L: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001; WBC < 4 × 10/L: OR = 0.30, 95% CI (0.17, 0.51), P < 0.00001].

Conclusion: Male, aged over 65, smoking patients might face a greater risk of developing into the critical or mortal condition and the comorbidities such as hypertension, diabetes, cardiovascular disease, and respiratory diseases could also greatly affect the prognosis of the COVID-19. Clinical manifestation such as fever, shortness of breath or dyspnea and laboratory examination such as WBC, AST, Cr, PCT, LDH, hs-cTnI and D-dimer could imply the progression of COVID-19.
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http://dx.doi.org/10.1016/j.jinf.2020.04.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177098PMC
August 2020

A novel ETV6-miR-429-CRKL regulatory circuitry contributes to aggressiveness of hepatocellular carcinoma.

J Exp Clin Cancer Res 2020 Apr 23;39(1):70. Epub 2020 Apr 23.

Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China.

Background: Tumor metastasis is one of the main causes of the high mortality of hepatocellular carcinoma (HCC). E-Twenty Six variant gene 6 (ETV6) is a strong transcriptional repressor, associated with the development and progression of tumors. However, the exact role and underlying mechanism of ETV6 in HCC remain unclear.

Methods: Western blotting, quantitative real-time PCR and immunohistochemistry were used to detect the expression levels of ETV6, CRKL (v-crk sarcoma virus CT10 oncogene homologue (avian)-like) and miR-429 in HCC tissues and cells; Transwell chamber and F-actin cytoskeleton staining assay to examine the effects of ETV6 and CRKL deregulation on the migration, invasion and cytoskeleton of HCC cells; Co-immunoprecipitation assay to determine the interaction between CRKL and ETV6; Chromatin immunoprecipitation assay to investigate the interaction between ETV6 and miR-429.

Results: We established a novel ETV6-miR-429-CRKL regulatory circuitry contributes to HCC metastasis. ETV6 and CRKL were frequently increased, while miR-429 was downregulated in both hepatocarcinoma tissues and hepatocarcinoma cells. Moreover, ETV6 upregulation was positively correlated with CRKL upregulation, and two negative correlations were also established for ETV6 and CRKL upregulation with miR-429 downregulation in both hepatocarcinoma patients' tumorous tissues and hepatocarcinoma cells. Functional investigations revealed that overexpression and knockdown of ETV6 was remarkably effective in promoting and suppressing HCC cell migration, invasion, cytoskeleton F-actin expression and arrangement, whereas, CRKL overexpression exhibited similar effects to the overexpression of ETV6. Mechanistically, ETV6 negatively regulates miR-429 expression by directly binding to the promoter region of miR-429; miR-429 negatively regulates CRKL expression by selectively targeting CRKL-3'-UTR; ETV6 directly binds to CRKL and positively regulates its expression, which in turn CRKL positively regulates ETV6 expression.

Conclusions: Our data demonstrated that ETV6 promotes migration and invasion of HCC cells by directly binding to promoter region of miR-429 via modulating CRKL expression. The newly identified ETV6-miR-429-CRKL regulatory circuitry contributes to the aggressiveness of HCC, which provides new clues for fundamental research on diagnosis and treatment parameters for HCC.
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http://dx.doi.org/10.1186/s13046-020-01559-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178969PMC
April 2020

Bidirectional interaction of lncRNA AFAP1-AS1 and CRKL accelerates the proliferative and metastatic abilities of hepatocarcinoma cells.

J Adv Res 2020 Jul 30;24:121-130. Epub 2020 Mar 30.

Department of Biochemistry, College of Basic Medical Sciences, Dalian Medical University, 9 West Section, Lvshun Southern Road, Dalian, Liaoning 116044, China.

Actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1), a long non-coding RNA transcribed from the antisense strand of protein coding gene AFAP1, has attracted attention in cancer research. Despite, its biological function and regulatory mechanism in hepatocellular carcinoma still unknown. The present study revealed AFAP1-AS1 mediated hepatocarcinoma progression through targeting CRKL. The bidirectional interaction of AFAP1-AS1 and oncogenic protein CRKL, and the deregulation of AFAP1-AS1 effects on Ras, MEK and c-Jun activities were investigated in depth. AFAP1-AS1 was upregulated in surgical tumorous tissues from hepatocarcinoma patients compared with the paired paracancerous non-tumor liver tissues, and in hepatocarcinoma Huh7, HCCLM3 and HepG2 cell lines compared with LO2, a normal liver cell line. AFAP1-AS1 knockdown noticeably suppressed the proliferative, migratory and invasive properties, and the epithelial-mesenchymal transition (EMT) process of HepG2 and HCCLM3 through upregulating E-cadherin and downregulating N-cadherin and vimentin. CRKL knockdown reduced AFAP1-AS1 expression levels in HepG2 and HCCLM3 cells. AFAP1-AS1 suppression impaired CRKL expression in HepG2 and HCCLM3. AFAP1-AS1 level change was positively correlated with the expression level changes of Ras, MEK and c-Jun in mediating the invasiveness of hepatocarcinoma cells. Current work demonstrated AFAP1-AS1 to be an applicable progression indicator of hepatocarcinoma. AFAP1-AS1 probably promotes the proliferation, EMT progression and metastasis of hepatocarcinoma cells CRKL mediated Ras/MEK/c-Jun and cadherin/vimentin signaling pathways. AFAP1-AS1-CRKL bidirectional feedback signaling is worthy of further study on the monitoring, diagnosis and treatment of cancers.
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http://dx.doi.org/10.1016/j.jare.2020.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139140PMC
July 2020

Matrine alleviates astrogliosis through sphingosine 1-phosphate signaling in experimental autoimmune encephalomyelitis.

Neurosci Lett 2020 01 10;715:134599. Epub 2019 Nov 10.

Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. Electronic address:

Expression of sphingosine/sphingosine 1-phosphate (SPH/S1P) in resident cells of the central nervous system plays an important role in the pathogenesis of multiple sclerosis (MS). Accumulated evidence has shown the protective effects of S1P receptor modulators on MS and its animal model, experimental autoimmune encephalomyelitis (EAE). However, effective therapies to regulate SPH/S1P molecules themselves have not been well addressed. Our previous studies showed that matrine (MAT), a natural alkaloid component extracted from the Sophora root, has beneficial effects in EAE through immunomodulation. Here we demonstrate that MAT alleviated astrogliosis in the CNS of EAE rats, and downregulated levels of SPH, S1P and S1P1 expression in CNS tissues and astrocytes. Expression of SPH kinases (SPHK) 1 and 2, which splice SPH into S1P, was also inhibited by MAT treatment. In vitro studies showed a direct inhibitory effect of MAT on S1P1 expression of activated astrocytes, suggesting that MAT could function as an S1PRs antagonist. Moreover, MAT upregulated the expression of plasma gelsolin, which combines with S1P to reduce its concentration. These findings indicate that MAT could alleviate astrogliosis in EAE through diminishing the SPH/SPHK/S1P1 pathway.
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http://dx.doi.org/10.1016/j.neulet.2019.134599DOI Listing
January 2020

CRKII overexpression promotes the proliferation, migration and invasion potential of murine hepatocarcinoma Hca-P cells.

Oncol Lett 2019 Jun 27;17(6):5169-5174. Epub 2019 Mar 27.

Department of Biochemistry, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.

Lymphatic metastasis is a major mechanism of tumor metastasis. The present study aimed to investigate the association of CRKII, a member of the CRK family, with the malignant behaviors of a murine hepatocarcinoma Hca-P cell line, with a lymph node metastatic rate of ~25%. Total mRNA was extracted from Hca-P cells, and then the murine CRKII gene was amplified by polymerase chain reaction and cloned into the pEASY-blunt cloning vector. Subsequently, the recombinant pcDNA3.1/V5-HisB-CRKII plasmid was constructed and transfected into Hca-P cells. Western blotting indicated that the CRKII expression level in pcDNA3.1/V5-HisB-CRKII-Hca-P cells was increased by ~185%, compared with pcDNA3.1/V5-HisB-Hca-P cells. The stable overexpression of CRKII enhanced the proliferation ability, as measured with a Cell Counting Kit-8 assay, and the colony forming capacity was measured with a soft agar colony forming assay for Hca-P cells. The migration and invasion capacities of Hca-P cells were increased by ~179 and 156% in Hca-P cells, respectively, following the stable upregulation of CRKII. Collectively, the recombinant pcDNA3.1/V5-HisB-CRKII-Hca-P plasmid was constructed successfully. Additionally, the CRKII expression level was positively associated with the proliferation, migration and invasion malignant properties of Hca-P cells.
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http://dx.doi.org/10.3892/ol.2019.10194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507350PMC
June 2019

miR-4521-FAM129A axial regulation on ccRCC progression through TIMP-1/MMP2/MMP9 and MDM2/p53/Bcl2/Bax pathways.

Cell Death Discov 2019 15;5:89. Epub 2019 Apr 15.

1Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, 116044 Dalian, China.

Clear cell renal cell carcinoma (ccRCC) is the most aggressive RCC subtype with high metastasis, chemotherapy and radiotherapy resistance, and poor prognosis. This study attempted to establish the deregulations of miR-4521 and FAM129A together with their correlation to and mechanism of regulation of ccRCC development and progression. FAM129A acted as tumor promotor and miR-4521 acted as a suppressor in ccRCC. As measured in surgical tumorous tissues from ccRCC patients, FAM129A overexpression and miR-4521 deficiency together contributed to ccRCC progression by promoting advances in patients' TNM stage and Fuhrman grade. Both the FAM129A knockdown and miR-4521 overexpression could reduce the in vitro migration and invasion abilities of renal cancer cells 786-O and ACHN, through the TIMP-1/MMP2/MMP9 pathway and could decrease their proliferation by promoting their apoptosis through the MDM2/p53/Bcl2/Bax pathway. By directly targeting the 3'-UTR domain of , miR-4521 was negatively correlated with /FAM129A levels in ccRCC progression and renal cancer cell malignancies. This work establishes the miR-4521-FAM129A axial regulation mechanism in ccRCC. Micro-4521 deficiency leads to /FAM129A upregulation, which synergistically enhances the migration and invasion of renal cancer cells due to the induced decrease of TIMP-1 and increases of MMP2 and MMP9, and increases their growth through escaping apoptosis by suppressing p53 by way of upregulation of induced MDM2. The current work provides new clues to assist fundamental research into the diagnosis and treatment of ccRCC.
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http://dx.doi.org/10.1038/s41420-019-0167-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465337PMC
April 2019

Autologous tumor cell-derived microparticle-based targeted chemotherapy in lung cancer patients with malignant pleural effusion.

Sci Transl Med 2019 01;11(474)

Key Laboratory of Pulmonary Diseases of Health Ministry, Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Cell membrane-derived microparticles (MPs), the critical mediators of intercellular communication, have gained much interest for use as natural drug delivery systems. Here, we examined the therapeutic potential of tumor cell-derived MPs (TMPs) in the context of malignant pleural effusion (MPE). TMPs packaging the chemotherapeutic drug methotrexate (TMPs-MTX) markedly restricted MPE growth and provided a survival benefit in MPE models induced by murine Lewis lung carcinoma and colon adenocarcinoma cells. On the basis of the potential benefit and minimal toxicity of TMPs-MTX, we conducted a human study of intrapleural delivery of a single dose of autologous TMPs packaging methotrexate (ATMPs-MTX) to assess their safety, immunogenicity, and clinical activity. We report our findings on 11 advanced lung cancer patients with MPE. We found that manufacturing and infusing ATMPs-MTX were feasible and safe, without evidence of toxic effects of grade 3 or higher. Evaluation of the tumor microenvironment in MPE demonstrated notable reductions in tumor cells and CD163 macrophages in MPE after ATMP-MTX infusion, which then translated into objective clinical responses. Moreover, ATMP-MTX treatment stimulated CD4 T cells to release IL-2 and CD8 cells to release IFN-γ. Our initial experience with ATMPs-MTX in advanced lung cancer with MPE suggests that ATMPs targeting malignant cells and the immunosuppressive microenvironment may be a promising therapeutic platform for treating malignancies.
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http://dx.doi.org/10.1126/scitranslmed.aat5690DOI Listing
January 2019

Research on High Performance Milling of Engineering Ceramics from the Perspective of Cutting Variables Setting.

Materials (Basel) 2019 Jan 2;12(1). Epub 2019 Jan 2.

Jiangsu Key Laboratory of Precision and Micro-Manufacturing Technology, Nanjing University of Aeronautics & Astronautics; Nanjing 210016, China.

The setting of cutting variables for precision milling of ceramics is important to both the machined surface quality and material removal rate (MRR). This work specifically aims at the performance of corner radius PCD (polycrystalline diamond) end mill in precision milling of zirconia ceramics with relatively big cutting parameters. The characteristics of the cutting zone in precision milling ceramics with corner radius end mill are analyzed. The relationships between the maximum uncut chip thickness () and the milling parameters including feed per tooth (), axial depth of cut () and tool corner radius () are discussed. Precision milling experiments with exploratory milling parameters that cause uncut chip thickness larger than the critical value were carried out. The material removal mechanism was also analyzed. According to the results, it is advisable to increase appropriately during precision milling ZrO₂ ceramics with corner radius end mill. There is still a chance to obtain ductile processed surface, as long as the brittle failure area is controlled within a certain range. The appropriate increasing of , not only can prevent the brittle damage from affecting the machined surface, but also could increase the MRR. The milling force increases with increasing MRR, but the surface roughness can still be stabilized within a certain range.
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http://dx.doi.org/10.3390/ma12010122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337323PMC
January 2019

A CpG oligodeoxynucleotide enhances the immune response to rabies vaccination in mice.

Virol J 2018 11 13;15(1):174. Epub 2018 Nov 13.

Key Laboratory for Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

Background: Rabies is a fatal disease that is preventable when post exposure prophylaxis (PEP) is administered in a timely fashion. CpG oligodeoxynucleotides (ODNs) can trigger cells that express Toll-like receptor 9, and their immunopotentiation activity in an inactivated aluminum-adjuvanted rabies vaccine for dogs has been identified using mouse and dog models.

Methods: A human diploid cell rabies vaccine (HDCV) of humans and a CpG ODNs with cross-immunostimulatory activity in humans and mice were used to evaluate the immunogenicity and protective efficacy of CpG ODN in a mouse model that simulates human PEP.

Results: HDCV combined with CpG ODN (HDCV-CpG) stimulated mice to produce rabies virus-specific neutralizing antibody (RVNA) earlier and increased the seroconversion rate. Compared with HDCV alone, either HDCV-1.25 μg CpG or HDCV-5 μg CpG increased the levels of RVNA. In particular, 5 μg CpG ODN per mouse significantly boosted the levels of RVNA compared with HDCV alone. IFN-γ producing splenocytes generated in the HDCV-5 μg CpG group were significantly increased compared to the group treated with HDCV alone. When the immunization regimen was reduced to three injections or the dose was reduced to half of the recommended HDCV combined with CpG ODN, the RVNA titers were still higher than those induced by HDCV alone. After viral challenge, 50% of mice immunized with a half-dose HDCV-CpG survived, while the survival rate of mice immunized with HDCV alone was 30%.

Conclusions: The immunopotentiation activity of CpG ODNs for a commercially available human rabies vaccine was first evaluated in a mouse model on the basis of the Essen regimen. Our results suggest that the CpG ODN used in this study is a potential adjuvant to rabies vaccines for human use.
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http://dx.doi.org/10.1186/s12985-018-1089-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234694PMC
November 2018

Retinoic Acid Receptor-Related Orphan Receptors: Critical Roles in Tumorigenesis.

Front Immunol 2018 31;9:1187. Epub 2018 May 31.

Key Laboratory of Respiratory Diseases of the Ministry of Health, Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Retinoic acid receptor-related orphan receptors (RORs) include RORα (NR1F1), RORβ (NR1F2), and RORγ (NR1F3). These receptors are reported to activate transcription through ligand-dependent interactions with co-regulators and are involved in the development of secondary lymphoid tissues, autoimmune diseases, inflammatory diseases, the circadian rhythm, and metabolism homeostasis. Researches on RORs contributing to cancer-related processes have been growing, and they provide evidence that RORs are likely to be considered as potential therapeutic targets in many cancers. RORα has been identified as a potential therapeutic target for breast cancer and has been investigated in melanoma, colorectal colon cancer, and gastric cancer. RORβ is mainly expressed in the central nervous system, but it has also been studied in pharyngeal cancer, uterine leiomyosarcoma, and colorectal cancer, in addition to neuroblastoma, and recent studies suggest that RORγ is involved in various cancers, including lymphoma, melanoma, and lung cancer. Some studies found RORγ to be upregulated in cancer tissues compared with normal tissues, while others indicated the opposite results. With respect to the mechanisms of RORs in cancer, previous studies on the regulatory mechanisms of RORs in cancer were mostly focused on immune cells and cytokines, but lately there have been investigations concentrating on RORs themselves. Thus, this review summarizes reports on the regulation of RORs in cancer and highlights potential therapeutic targets in cancer.
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http://dx.doi.org/10.3389/fimmu.2018.01187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990620PMC
August 2019

Annexin A5 regulates hepatocarcinoma malignancy via CRKI/II-DOCK180-RAC1 integrin and MEK-ERK pathways.

Cell Death Dis 2018 05 25;9(6):637. Epub 2018 May 25.

Department of Biotechnology, Dalian Medical University, 9 West Section, Lvshun Southern Road, Dalian, 116044, China.

As a calcium-dependent phospholipid binding annexin protein, annexin A5 (Anxa5) links to the progression, metastasis, survival, and prognosis of a variety of cancers. Current work showed ANXA5 overexpression was positively correlated with the upregulations of CRKI/II and RAC1 in hepatocarcinoma (HCC) patients' tissues, which potentially enhanced the clinical progression and lymphatic metastasis of HCC. The role and action mechanism of ANXA5 in hepatocarcinoma was then investigated using a hepatocarcinoma Hca-P cell line, an ideal and well-established murine cell model with 100% inducible tumorigenicity of implanted mice with low (~25%) lymph node metastatic (LNM) rate. In vitro evidences indicated ANXA5 stable knockdown resulted in decreased proliferation, migration, invasion and adhesion to lymph node (LN), and increased intercellular cohesion behaviors of hepatocarcinoma Hca-P cells. Consistently, stable ANXA5 knockdown led to reduced in vivo tumorigenicity and malignancy, LNM rate and level potentials of Hca-P- transplanted mice via inhibiting CD34 and VEGF3. The levels of CRKI/II and RAC1 were reduced in tumor tissues from mice transplanted with Hca-P cells with stable ANXA5 knockdown. Molecular action investigation further showed ANXA5 downregulation apparently suppressed the expressions of molecules CRKI/II, DOCK180, RAC1 in integrin pathway, p-MEK, p-ERK, c-Myc, and MMP-9 in MEK- ERK pathway together with VIMINTIN in Hca-P cells in appropriate to knockdown extent. Collectively, Anxa5 was able to mediate HCC carcinogenesis via integrin and MEK-ERK pathways. It is of potential use in the research and treatment of HCC.
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http://dx.doi.org/10.1038/s41419-018-0685-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970249PMC
May 2018

miR-429 suppresses tumor migration and invasion by targeting CRKL in hepatocellular carcinoma via inhibiting Raf/MEK/ERK pathway and epithelial-mesenchymal transition.

Sci Rep 2018 02 5;8(1):2375. Epub 2018 Feb 5.

Department of Biotechnology, Dalian Medical University, Dalian, Liaoning, 116044, China.

Tumor metastasis is one of the main causes of hepatocellular carcinoma (HCC) high mortality. CRKL (v-crk sarcoma virus CT10 oncogene homologue (avian)-like) play important roles in tumor metastasis, however, the exact role and underlying mechanism of CRKL in HCC is still unknown. In our study, we demonstrated miR-429 negatively regulated CRKL expression via selectively binding to CRKL-3'-UTR at 3728-3735 bp site by post-transcriptionally mediating its functionality. Re-expression and silencing of miR-429 was remarkably effective in suppressing and promoting HepG2 cell migration and invasion in vitro. Knockdown or overexpression of CRKL exhibited similar effects as the overexpression or silencing of miR-429, whereas, CRKL overexpression (without the 3'-UTR) abrogated miR-429-induced inhibition on HepG2 migration and invasion. Moreover, miR-429-CRKL axis affected HepG2 migration and invasion potentials by regulating the adhesion ability, cytoskeleton F-actin expression and arrangement of HepG2. Furthermore, interference of Raf/MEK/ERK pathway and EMT contributed to miR-429-CRKL axis mediated metastasis inhibition. Nevertheless, miR-429 could not inhibit HepG2 proliferation through CRKL/c-Jun pathway. Taken together, our data demonstrated that miR-429 might function as an antimetastatic miRNA to regulate HCC metastasis by directly targeting CRKL via modulating Raf/MEK/ERK-EMT pathway. The newly identified miR-429-CRKL axis represents a novel potential therapeutic target for HCC treatment.
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http://dx.doi.org/10.1038/s41598-018-20258-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5799248PMC
February 2018

Recombinant Mtb9.8 of Mycobacterium bovis stimulates TNF-α and IL-1β secretion by RAW264.7 macrophages through activation of NF-κB pathway via TLR2.

Sci Rep 2018 01 31;8(1):1928. Epub 2018 Jan 31.

Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, P. R. China.

The Mtb9.8 antigenic protein of Mycobacterium bovis/Mycobacterium tuberculosis has been identified as a target of the T-cell response. However, the interaction of Mtb9.8 with Toll-like receptors (TLRs) and the relevant signaling pathways have not been fully clarified. In this study, recombinant Mtb9.8 (rMtb9.8) derived from M. bovis-stimulated RAW264.7 cells initiated the secretion of TNF-α and IL-1β in a dose-dependent manner. Blocking assays show that TLR2-neutralizing antibody decreases the production of TNF-α and IL-1β. Moreover, NF-κB activation is associated with TNF-α and IL-1β production by rMtb9.8 stimulation, and rMtb9.8 stimulation also induces the phosphorylation of NF-κB p65 at Ser536 and its rapid nuclear translocation in RAW264.7 cells. Furthermore, NF-κB luciferase activity is rapidly activated in response to rMtb9.8 in RAW264.7 cells and is also significantly increased in rMtb9.8-induced HEK293-TLR2. However, these activations were abrogated in cells with a dominant-negative mutation of NF-κB p65 and by treatment with anti-TLR2 antibody. We also find that rMtb9.8 induces the activation of IRF-1. These findings indicate that M. bovis-derived rMtb9.8 activates the NF-κB pathway via TLR2 in RAW264.7 cells. In particular, it phosphorylates NF-κB p65 at Ser536 and induces nuclear translocation, thereby leading to the production of TNF-α and IL-1β, which correlates with the induction of IRF-1.
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http://dx.doi.org/10.1038/s41598-018-20433-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5792469PMC
January 2018

Value of F-FDG PET/CT for predicting EGFR mutations and positive ALK expression in patients with non-small cell lung cancer: a retrospective analysis of 849 Chinese patients.

Eur J Nucl Med Mol Imaging 2018 05 21;45(5):735-750. Epub 2017 Nov 21.

Key Laboratory of Respiratory Diseases of the Ministry of health, Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.

Purpose: Epidermal growth factor receptor (EGFR) mutations and the anaplastic lymphoma kinase (ALK) rearrangement are the two most common druggable targets in non-small cell lung cancer (NSCLC). However, genetic testing is sometimes unavailable. Previous studies regarding the predictive role of F-FDG PET/CT for EGFR mutations in NSCLC patients are conflicting. We investigated whether or not F-FDG PET could be a valuable noninvasive method to predict EGFR mutations and ALK positivity in NSCLC using the largest patient cohort to date.

Methods: We retrospectively reviewed and included 849 NSCLC patients who were tested for EGFR mutations or ALK status and subjected to F-FDG PET/CT prior to treatment. The differences in several clinical characteristics and three parameters based on F-FDG PET/CT, including the maximal standard uptake value (SUV) of the primary tumor (pSUV), lymph node (nSUV) and distant metastasis (mSUV), between the different subgroups were analyzed. Multivariate logistic regression analysis was performed to identify predictors of EGFR mutations and ALK positivity.

Results: EGFR mutations were identified in 371 patients (45.9%). EGFR mutations were found more frequently in females, non-smokers, adenocarcinomas and stage I disease. Low pSUV, nSUV and mSUV were significantly associated with EGFR mutations. Multivariate analysis demonstrated that pSUV < 7.0, female sex, non-smoker status and adenocarcinoma were predictors of EGFR mutations. The receiver operating characteristic (ROC) curve yielded area under the curve (AUC) values of 0.557 and 0.697 for low pSUV alone and the combination of the four factors, respectively. ALK-positive patients tended to have a high nSUV. Younger age and distant metastasis were the only two independent predictors of ALK positivity.

Conclusion: We demonstrated that low pSUVmax is associated with mutant EGFR status and could be integrated with other clinical factors to enhance the discriminability on the EGFR mutation status in some NSCLC patients whose EGFR testing is unavailable.
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http://dx.doi.org/10.1007/s00259-017-3885-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978918PMC
May 2018

Coinfection with Haemophilus parasuis serovar 4 increases the virulence of porcine circovirus type 2 in piglets.

Virol J 2017 11 21;14(1):227. Epub 2017 Nov 21.

State Key Laboratory of Agricultural Microbiology, College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.

Background: Postweaning multisystemic wasting syndrome (PMWS) is an emerging disease in swine. Pigs with PMWS are often infected with a variety of other pathogens, including bacteria, viruses and mycoplasm, in addition to porcine circovirus type 2 (PCV2). PCV2 and Haemophilus parasuis serovar 4 (HPS4) coinfection remain epidemic in China.

Methods: Here we report construction of a three-week-old naturally farrowed, colostrum-deprived (NFCD) piglet's infection model and demonstrate that PCV2-infected piglets with the HPS4 coinfection increased the virulence of PCV2 and these pathogens interact acquired PMWS.

Results: All the single infected piglets were transiently bacteremic or viremic. All the PCV2/HPS4 coinfected piglets developed PMWS, characterized by dyspnea, anorexia, prostration and lose weight severely. Co-infection with PCV2 and HPS4 resulted in an increased amount of virus in serum and tissues, presented a slower generation and lower levels of antibodies against PCV2. Co-infection with PCV2 and HPS4 resulted in further reductions in total and differential peripheral blood leukocyte counts. Meantime, PCV2/ HPS4 coinfection potentiated the severity of lung and lymphoid lesions by PCV2-associated, increased the virulence of PCV2-antigen and enhanced the incidence of PMWS in piglets.

Conclusion: Co-infection with PCV2 and HPS4 induce the exacerbation of system injuries and enhance the pathogenicity of PCV2 in piglets.
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http://dx.doi.org/10.1186/s12985-017-0890-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696968PMC
November 2017

Role of systemic injection of rabies immunoglobulin in rabies vaccination.

Arch Virol 2017 Jun 10;162(6):1701-1703. Epub 2017 Feb 10.

Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changbai Road 155, Changping District, Beijing, 102206, People's Republic of China.

To determine the role of systemic injection of rabies immunoglobulin (RIG) in rabies vaccination, we analyzed the level of antibody against rabies virus in the serum of mice that received various doses of RIG combined with rabies vaccine. Our results indicate that systemic injection of RIG does not contribute detectably to passive or adaptive immunization, suggesting that the main function of RIG in individuals with category III exposure is to neutralize rabies virus via immediate local infiltration of the wound.
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http://dx.doi.org/10.1007/s00705-017-3263-yDOI Listing
June 2017

[Preparation and Preliminary Application of a Virus Library for the Neutralizing Activity of a Monoclonal Antibody Against the Rabies Virus].

Bing Du Xue Bao 2016 11;32(6):790-5

To establish a method for measurement of the neutralizing activity of a monoclonal antibody against the rabies virus. Twenty-four rabies street virus-positive samples were isolated by the mouse inoculation test. Isolated rabies street viruses were cultured and the virus titer tested in N2A cells. We established a rabies street virus bank with viruses that could adapt to the growth of N2A cells with a high titer. Then repeatability was evaluated after three detections of the TRN006 monoclonal antibody. Of the 24 positive samples,15 strains of the virus could adapt to N2A cells and form fluorescent foci in cells.Finally,10 strains with a high titer were selected for the rabies street virus bank, which covered nine Provinces of China and four Chinese lineages. Three lineages were used for the neutralization test for the monoclonal antibody, and the Student’s t-test showed that it had good repeatability.
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November 2016

Anxa5 mediates the in vitro malignant behaviours of murine hepatocarcinoma Hca-F cells with high lymph node metastasis potential preferentially via ERK2/p-ERK2/c-Jun/p-c-Jun(Ser73) and E-cadherin.

Biomed Pharmacother 2016 Dec 30;84:645-654. Epub 2016 Sep 30.

Department of Biotechnology, Dalian Medical University, Dalian 116044, China. Electronic address:

Objective: Annexin A5 (Anxa5) is associated with the progression of some cancers, while its role and regulation mechanism in tumor lymphatic metastasis is rarely reported. This study aims to investigate the influence of Anxa5 knockdown on the malignant behaviours of murine hepatocarcinoma Hca-F cell line with high lymph node metastatic (LNM) potential and the underlying regulation mechanism.

Methods: RNA interfering was performed to silence Anxa5 in Hca-F. Monoclonal shRNA-Anxa5- Hca-F cells were obtained via G418 screening by limited dilution method. Quantitative real-time RT-PCR (qRT-PCR) and Western blotting (WB) were applied to measure Anxa5 expression levels. CCK-8, Boyden transwell-chamber and in situ LN adhesion assays were performed to explore the effects of Anxa5 on the proliferation, migration, invasion and adhesion capacities of Hca-F. WB and qRT-PCR were used to detect the level changes of key molecules in corresponding signal pathways.

Results: We obtained two monoclonal shRNA-Anxa5-transfected Hca-F cell lines with stable knockdowns of Anxa5. Anxa5 knockdown resulted in significantly reduced proliferation, migration, invasion and in situ LN adhesion potentials of Hca-F in proportion to its knockdown extent. Anxa5 downregulation enhanced E-cadherin levels in Hca-F. Moreover, Anxa5 affected Hca-F behaviours specifically via ERK2/p-ERK2/c-Jun/p-c-Jun(Ser73) instead of p38MAPK/c-Jun, Jnk/c-Jun and AKT/c-Jun pathways.

Conclusions: Anxa5 mediates the in vitro malignant behaviours of murine hepatocarcinoma Hca-F cells via ERK2/c-Jun/p-c-Jun(Ser73) and ERK2/E-cadherin pathways. It is an important molecule in metastasis (especially LNM) and a potential therapeutic target for hepatocarcinoma.
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http://dx.doi.org/10.1016/j.biopha.2016.09.086DOI Listing
December 2016

Formyl-Modified Polyaniline for the Catalytic Dehydration of Fructose to 5-Hydroxymethylfurfural.

ChemSusChem 2016 08 25;9(16):2174-81. Epub 2016 Jul 25.

Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, Sichuan, 610064, PR China.

We report an unprecedented solid organic-base catalyst, formyl-modified polyaniline (FS-PAN), for the dehydration of fructose to 5-hydroxymethylfurfural (HMF) with a high yield of 90.4 mol %. We demonstrate that the nitrogen atoms incorporated between the phenyl rings in the backbone of the polyaniline chain contribute to the basicity of the catalyst. The grafting of electron-withdrawing formyl groups to the imine nitrogen atoms leads to a significant increase of basicity of the polymer catalyst owing to the greater localization of electrons at the amide nitrogen atom formed. A linear dependence of the yield of HMF on the grafting level of formyl groups in FS-PAN indicates that the amide acts as the active phase. A possible reaction mechanism for this organic-base-catalyzed dehydration reaction is proposed. The side-reaction of HMF rehydration is inhibited thoroughly, and the condensation of any reaction intermediates to undesirable oligomers is restrained by this base catalyst. This organic-base catalyst can be recycled completely without loss of activity. This research highlights the first application of a highly effective and stable solid base catalyst for the transformation of renewable carbohydrates into fine chemicals.
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http://dx.doi.org/10.1002/cssc.201600503DOI Listing
August 2016