Publications by authors named "Xiangsheng Li"

20 Publications

  • Page 1 of 1

RIPK1 regulates cell function and death mediated by UVB radiation and TNF-α.

Mol Immunol 2021 Jul 5;135:304-311. Epub 2021 May 5.

College of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Institute of Life Science and Green Development, Hebei University, Baoding, 071002, China. Electronic address:

The RIP family plays a key role in mediating cell inflammation, oxidative stress and death. Among them, RIPK1, as an important regulatory factor in the upstream of the NF-κB pathway, is involved in multiple pathways of cell inflammation and death. Epidermal cells constitute the outermost barrier of the human body. Radiation can induce epidermal cell death, inflammation and oxidative stress to cause damage. Therefore, this paper selected HaCaT cell and used CRISPR/Cas technology to construct a cell model of stable knockout of RIPK1 gene, to analyze the effect and regulation of RIPK1 knockout on the function and death of HaCaT cells induced by UVB or TNF-α. The results showed that knockout of RIPK1 had no significant effect on the morphology of HaCaT cells at rest, but it led to slowing cell proliferation and blocking the G2M phase of cell cycle. Compared with HaCaT, HaCaT was abnormally sensitive to TNF-α-induced cell death and apoptosis, and may be associated with inhibition of NF-κB pathway. Knocking out RIPK1 led to a more significant inhibition of cell growth by UVB, and up-regulation of the expression of the inflammatory factor IL-1α. P38 MAPK and NF-κB pathways may be involved this process. This study further found that RIPK1 in epidermal cell has a regulatory function on pro-survival signals.
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http://dx.doi.org/10.1016/j.molimm.2021.04.024DOI Listing
July 2021

Identification of Immune-Related Prognostic Biomarkers Associated with HPV-Positive Head and Neck Squamous Cell Carcinoma.

J Immunol Res 2021 8;2021:6661625. Epub 2021 Jan 8.

Department of Otolaryngology Head and Neck Surgery, Affiliated Changsha Hospital of Hunan Normal University, 70 Lushan Road, Changsha, Hunan 410013, China.

Background: As a type of malignant tumor, head and neck squamous cell carcinoma (HNSCC) seriously threatens human health. This study is aimed at constructing a new, reliable prognostic model.

Method: The gene expression profile data of HNSCC patients were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The immune-related differentially expressed genes (IRDEGs) related to HNSCC were identified. We then used Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis to explore IRDEGs related to the HNSCC prognosis and to construct and validate a risk scoring model and used ESTIMATE to evaluate tumor immune infiltration in HNSCC patients. Finally, we validated IGSF5 expression and function in HNSCC cells.

Results: A total of 1,195 IRDEGs were found from the GSE65858 dataset. Thirty-one of the 1,195 IRDEGs were associated with the prognosis of HNSCC. Nine key IRDEGs were further selected using the LASSO method, and a risk scoring model was established for predicting the survival of HNSCC patients. According to the risk scoring model, the prognosis of patients in the high-risk group was worse than that of the low-risk group; the high-risk group had significantly higher immune scores than the low-risk group; and between the high- and low-risk samples, there were significant differences in the proportion of 10 types of cells, including naive cells, plasma cells, and resting CD4 memory T cells. IGSF5 has low expression in HNSCC, and overexpression of IGSF5 significantly impaired HNSCC cell proliferation.

Conclusion: This prognostic risk assessment model can help systematically evaluate the survival prognosis of HNSCC patients and provides a new research direction for the improvement of the survival prognosis of HNSCC patients in clinical practice.
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http://dx.doi.org/10.1155/2021/6661625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810542PMC
January 2021

The role of the tyrosine kinase Lyn in allergy and cancer.

Mol Immunol 2021 03 6;131:121-126. Epub 2021 Jan 6.

College of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Institute of Life Science and Green Development, Hebei University, Baoding, 071002, China. Electronic address:

With worsening air pollution brought by global social development, the prevalence of allergic diseases has increased dramatically in the past few decades. The novel Lck/yes-related protein tyrosine kinase (Lyn) belongs to the Src kinase family (SFK) and plays a pivotal role in the pathogenesis of inflammation, tumor, and allergy. This signaling molecule is vital in the IgE/FcεRI signaling pathway that regulates allergy. The Lyn-FcεRIβ interaction is essential for mast cell activation. The signaling pathway of Lyn has become the focus of immune, inflammatory, tumor, and allergy research. This molecule has positive and negative regulatory effects, which have attracted researchers' attention. This paper reviews the basic characteristics of Lyn and its regulatory mechanism and role in tumor and other diseases, specifically in allergies.
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http://dx.doi.org/10.1016/j.molimm.2020.12.028DOI Listing
March 2021

microRNA-18a from M2 Macrophages Inhibits TGFBR3 to Promote Nasopharyngeal Carcinoma Progression and Tumor Growth via TGF-β Signaling Pathway.

Nanoscale Res Lett 2020 Oct 2;15(1):196. Epub 2020 Oct 2.

Department of Otolaryngology Head and Neck Surgery, Third Xiangya Hospital, Central South University, 138th Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, People's Republic of China.

Objectives: Nasopharyngeal carcinoma (NPC) is a type of nasopharyngeal disease with high metastasis and invasion properties. Tumor-associated alternative activated (M2) macrophages are evidenced to connect with NPC. Based on this, this study purposes to explore the mechanism and participation of microRNA-18a (miR-18a) from M2 macrophages in NPC.

Methods: Peripheral blood mononuclear cells were differentiated to macrophages and macrophages were polarized to M2 type by interleukin-4. SUNE-1 and CNE2 cells were transfected with restored or depleted miR-18a or transforming growth factor-beta III receptor (TGFBR3) to explore their roles in NPC progression with the involvement of the TGF-β signaling pathway. Next, SUNE-1 and CNE2 cells were co-cultured with M2 macrophages that had been treated with restored or depleted miR-18a or TGFBR3 to comprehend their combined roles in NPC with the involvement of the TGF-β signaling pathway.

Results: MiR-18a was highly expressed and TGFBR3 was lowly expressed in NPC cells. MiR-18a restoration, TGFBR3 knockdown or co-culture with miR-18a mimics, or si-TGFBR3-transfected M2 macrophages promoted SUNE-1 cell progression, tumor growth in mice, decreased p-Smad1/t-Smad1, and elevated p-Smad3/t-Smad3. miR-18a downregulation, TGFBR3 overexpression, or co-culture with miR-18a inhibitors or OE-TGFBR3-transfected M2 macrophages depressed CNE2 cell progression, tumor growth in mice, increased p-Smad1/t-Smad1, and decreased p-Smad3/t-Smad3.

Conclusion: Our study elucidates that miR-18a from M2 macrophages results in promoted NPC cell progression and tumor growth in nude mice via TGFBR3 repression, along with the Smad1 inactivation and Smad3 activation.
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http://dx.doi.org/10.1186/s11671-020-03416-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532261PMC
October 2020

Cross-talk of Signaling Pathways in the Pathogenesis of Allergic Asthma and Cataract.

Protein Pept Lett 2020 ;27(9):810-822

College of Pharmaceutical Sciences, Hebei University, Baoding 071002, China.

Allergic asthma is a chronic inflammatory disease, which involves many cellular and cellular components. Cataract is a condition that affects the transparency of the lens, which the opacity of the lens caused by any innate or acquired factor degrades its transparency or changes in color. Both of them belong to diseases induced by immune disorders or inflammation. We want to confirm the signaling pathways involved in the regulation of asthma and cataract simultaneously, and provide reference for the later related experiments. So we conducted a scoping review of many databases and searched for studies (Academic research published in Wiley, Springer and Bentham from 2000 to 2019) about the possible relationship between asthma and cataract. It was found that during the onset of asthma and cataract, Rho/Rock signaling pathway, Notch signaling pathway, Wnt/β-catenin signaling pathway, PI3K/AKT signaling pathway, JAK/STAT signaling pathway, MAPK signaling pathway, TGF-β1/Smad signaling pathway and NF-κB signaling pathway are all active, so they may have a certain correlation in pathogenesis. Asthma may be associated with cataract through the eight signaling pathways, causing inflammation or immune imbalance based on allergy that can lead to cataract. According to these studies, we speculated that the three most likely signaling pathways are PI3K/AKT, MAPK and NF-κB signaling pathway.
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http://dx.doi.org/10.2174/0929866527666200207113439DOI Listing
February 2021

PI3K-AKT-mTOR signaling pathway: the intersection of allergic asthma and cataract.

Pharmazie 2019 10;74(10):598-600

Allergic asthma is a chronic inflammatory disease and involves many cells and cellular components. Cataract is a condition that affects the transparency of the lens, which the opacity of the lens caused by any innate or acquired factor degrades its transparency or changes in color. During the establishment of asthma model of rats with chicken ovalbumin nebulization, it was found that asthmatic rats were more likely to have monocular or binocular cataract symptoms than normal rats. Considering that they are all induced by immune imbalance, inflammation, etc., there may be some correlation in the mechanism, and many clues showed that both diseases are associated with activation of the PI3K-AKT-mTOR signaling pathway. Therefore, we hypothesized that the PI3K-AKT-mTOR signaling pathway produces inflammatory or immune imbalance based on allergy leading to cataract.
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http://dx.doi.org/10.1691/ph.2019.9080DOI Listing
October 2019

Species Specificity on Interaction between IgE and FcεRI.

Curr Pharm Biotechnol 2019 ;20(9):690-695

College of Pharmaceutical Sciences, Hebei University, Baoding 071002, China.

Allergic diseases are one of the most prevalent diseases at present, it is imperative to understanding the pathophysiology and treatment strategies for allergic diseases. In this process, the binding of IgE and FcεRI on effector cells plays a critical role in triggering allergic reactions. However, the species specificity of the interaction between IgE and FcεRI has not been clearly explained. This review described the characteristics and the interaction mechanism in the allergic reaction of IgE and FcεRI and summarized the species specificity between IgE and FcεRI.
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http://dx.doi.org/10.2174/1389201020666190619122325DOI Listing
January 2020

Intravoxel Incoherent Motion Combined With Dynamic Contrast-Enhanced Perfusion MRI of Early Cervical Carcinoma: Correlations Between Multimodal Parameters and HIF-1α Expression.

J Magn Reson Imaging 2019 09 16;50(3):918-929. Epub 2019 Jan 16.

Department of MR Research, GE Healthcare, Beijing, China.

Background: The identification of hypoxia inducible factor (HIF-1α) expression is helpful for the quantitative assessment of tumor hypoxia. The application of multimodal imaging techniques may play a part in the assessment of HIF-1α expression of cervical carcinoma.

Purpose: To investigate the correlations between multiple imaging parameters and HIF-1α expression of early cervical carcinoma and to determine whether tumor hypoxia can be predicted using multisequence imaging parameters.

Study Type: Prospective observational.

Population: One hundred patients with early cervical carcinoma.

Field Strength/sequences: 3.0 T MRI including intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) perfusion MRI sequences.

Assessment: DCE-MRI and IVIM DWI were performed for all patients. The imaging parameters included volume transfer constant (K ), rate constant (K ), extravascular extracellular volume fraction (V ), D, D*, and f.

Statistical Tests: The comparisons of imaging parameters between two independent groups were performed using the Mann-Whitney U-test. Multiple linear regression analysis was performed to determine the correlation between multiple imaging parameters and HIF-1α expression. The diagnostic ability of DCE-MRI, IVIM DWI, and the combination of two techniques for discriminating high-expression and low-expression groups were analyzed.

Results: The high-expression group had a lower K or K value than the low-expression group (P = 0.03; 0.02), while the high-expression group had a higher V value than the low-expression group (P = 0.03). The high-expression group had a higher D or f value than the low-expression group (P = 0.02; 0.02). K , K , D, V , and f values were independently correlated with HIF-1α expression. The sensitivity or accuracy of a combined method was higher than that of DCE-MRI or IVIM DWI individually (P = 0.03, 0.02; 0.04, 0.03).

Data Conclusion: The combination of DCE-MRI and IVIM DWI can improve the diagnostic ability of discriminating different HIF-1α expression levels for early cervical tumors.

Level Of Evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:918-929.
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http://dx.doi.org/10.1002/jmri.26604DOI Listing
September 2019

Long noncoding RNA FOXD2-AS1 promotes glioma malignancy and tumorigenesis via targeting miR-185-5p/CCND2 axis.

J Cell Biochem 2019 06 5;120(6):9324-9336. Epub 2018 Dec 5.

Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China.

Glioma is the most aggressive malignant tumor in the adult central nervous system. Abnormal long noncoding RNA (lncRNA) FOXD2-AS1 expression was associated with tumor development. However, the possible role of FOXD2-AS1 in the progression of glioma is not known. In the present study, we used in vitro and in vivo assays to investigate the effect of abnormal expression of FOXD2-AS1 on glioma progression and to explore the mechanisms. FOXD2-AS1 was upregulated in glioma tissue, cells, and sphere subpopulation. Upregulation of FOXD2-AS1 was correlated with poor prognosis of glioma. Downregulation of FOXD2-AS1 decreased cell proliferation, migration, invasion, stemness, and epithelial-mesenchymal transition (EMT) in glioma cells and inhibited tumor growth in transplanted tumor. We also revealed that FOXD2-AS1 was mainly located in cytoplasm and microRNA (miR)-185-5p both targeted FOXD2-AS1 and CCND2 messenger RNA (mRNA) 3'-untranslated region (3'-UTR). miR-185-5p was downregulated in glioma tissue, cells, and sphere subpopulation. Downregulation of miR-185-5p was closely correlated with poor prognosis of glioma patients. In addition, miR-185-5p mimics decreased cell proliferation, migration, invasion, stemness, and EMT in glioma cells. CCND2 was upregulated in glioma tissue, cells, and sphere subpopulation. Upregulation of CCND2 was closely correlated with poor prognosis of glioma patients. CCND2 knockdown decreased cell proliferation, migration, invasion, and EMT in glioma cells. In glioma tissues, CCND2 expression was negatively associated with miR-185-5p, but positively correlated with FOXD2-AS1. FOXD2-AS1 knockdown and miR-185-5p mimics decreased CCND2 expression. Inhibition of miR-185-5p suppressed FOXD2-AS1 knockdown-induced decrease of CCND2 expression. Overexpression of CCND2 suppressed FOXD2-AS1 knockdown-induced inhibition of glioma malignancy. Taken together, our findings highlight the FOXD2-AS1/miR-185-5p/CCND2 axis in the glioma development.
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http://dx.doi.org/10.1002/jcb.28208DOI Listing
June 2019

p38 Inhibitor Protects Mitochondrial Dysfunction by Induction of DJ-1 Mitochondrial Translocation After Subarachnoid Hemorrhage.

J Mol Neurosci 2018 Oct 21;66(2):163-171. Epub 2018 Sep 21.

Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, Henan, China.

p38 mitogen-activated protein kinase (MAPK) is a major player in mitochondrial dysfunction after subarachnoid hemorrhage (SAH). Moreover, DJ-1, which responds to oxidative stress and translocates to mitochondria, maintains mitochondrial homeostasis. Although a few studies have demonstrated that DJ-1 indirectly regulates p38 activation, the relationship between DJ-1 and p38 in mitochondrial dysfunction after SAH has not been delineated. Using an in vitro SAH model, alterations in p38, p-p38, DJ-1, and autophagic-related protein expression were detected. As expected, p38 inhibitor significantly blocked excessive expression of p38 and p-p38 after SAH, whereas total DJ-1 expression and mitochondrial DJ-1 were up-regulated. Further analysis showed that p38 inhibitor significantly blocked oxyhemoglobin (OxyHb) induced mitochondrial dysfunction, including mitochondrial membrane potential depolarization and reactive oxygen species (ROS) release. In addition, p38 inhibitor restored OxyHb-induced abnormal autophagic flux at the initiation and formation stage by regulating Atg5, beclin-1, the ratio of LC3-II/LC3-I, and p62 expression. This study suggested that overexpression of p38 induced the accumulation of mitochondrial dysfunction partly due to abnormal activation of autophagy, which largely relied on DJ-1 mitochondrial translocation.
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http://dx.doi.org/10.1007/s12031-018-1131-1DOI Listing
October 2018

Aryl Hydrocarbon Receptor Activation Modulates Intestinal Epithelial Barrier Function by Maintaining Tight Junction Integrity.

Int J Biol Sci 2018 11;14(1):69-77. Epub 2018 Jan 11.

Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.

Activation of Aryl hydrocarbon receptor (AhR) is involved in the control of intestinal mucosal homeostasis. Intestinal barrier dysfunction contributes to the development of many intestinal diseases, such as inflammatory bowel disease (IBD). In this study, we investigated the mechanisms of AhR activation in the maintenance of intestinal barrier function. Adult C57BL/6 mice were treated with dextran sulphate sodium (DSS) for 7 days, with or without 6-Formylindolo(3,2-b)carbazole (FICZ), a ligand of AhR. We found that AhR activation by FICZ attenuated the decreased TJ protein expression in the colonic mucosa of the DSS-induced mice. Further, the increase of both MLC phosphorylation and MLCK expression in the mice with DSS-induced colitis was also significantly inhibited by FICZ induced AhR activation. For experiments, Caco-2 cells were treated with tumour necrosis factor alpha (TNF-α)/interferon gamma (IFN-γ) for 48 h, with or without FICZ. AhR activation prevented TNF-α/IFN-γ-induced decrease in TER and morphological disruption of the TJs in Caco-2 monolayers. It also inhibited TNF-α/IFN-γ-induced increase in MLCK expression and MLC phosphorylation by suppression of NF-κB p65 signaling pathway. Thus, AhR-activating factors might have potential as therapeutic agents for the treatment of patients with IBD.
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http://dx.doi.org/10.7150/ijbs.22259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821050PMC
February 2019

Intravoxel incoherent motion MR imaging of early cervical carcinoma: correlation between imaging parameters and tumor-stroma ratio.

Eur Radiol 2018 May 8;28(5):1875-1883. Epub 2017 Dec 8.

Department of Medical Imaging, Cancer Hospital of China Medical University & Liaoning Cancer Hospital & Institute, No.44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, People's Republic of China.

Objectives: To investigate if intravoxel incoherent motion (IVIM) MR imaging can predict the tumour-stroma ratio (TSR) in patients with early cervical carcinoma.

Methods: Fifty-four patients with early cervical carcinoma were prospectively enrolled into this study. All patients underwent IVIM imaging and parameters including D, D* and f value were measured. The tumours were classified into stroma-rich and stroma-poor group according to TSR, and comparisons of IVIM parameters between two groups were performed. The relationships between IVIM parameters and TSR were analysed by using a multivariate multi-regression analysis.

Results: D and f values were significantly lower in stroma-poor tumours than in stroma-rich tumours (p=0.02, 0.04), while the difference in D* value between two groups didn't achieve statistical significance (p=0.09). The areas under ROC curves of D and f values in discriminating stroma-rich and stroma-poor tumours were 0.835 (95%CI=0.616~0.905) and 0.686 (95%CI=0.575~0.798). In multiple linear regression analysis, D value, pathologic type, histologic grade, tumour size and f value were independently correlated with TSR of cervical carcinoma.

Conclusions: D and f values are independently correlated with TSR of cervical carcinoma and have the potential for quantitative measurement of TSR.

Key Points: • TSR is a recognized independent prognostic factor in many solid tumours. • D and f values measured by IVIM MRI are independently correlated with TSR while D* is not. • IVIM offers the potential to predict TSR.
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http://dx.doi.org/10.1007/s00330-017-5183-3DOI Listing
May 2018

PQ401, an IGF-1R inhibitor, induces apoptosis and inhibits growth, proliferation and migration of glioma cells.

J Chemother 2016 ;28(1):44-9

a Department of Neurosurgery , First Affiliated Hospital of Xinxiang Medical College , Weihui , Henan , P. R. China.

Growth factor signalling pathways transduce extra-cellular physiological cues to guide cells to maintain critical cellular functions, including cell proliferation, survival and metabolism. Dysregulation of certain growth factor signalling pathways has been shown as a major route to promote tumourigenesis. Glioma is a type of aggressive malignant tumour with no effective systematic therapy so far. Overexpression or hyperactivation of IGF-1R has been observed to be tightly associated with glioma progression and poor prognosis. Here, we examined the biological effects of a specific IGF-1R inhibitor, PQ401, on suppressing U87MG glioma cell growth and migration. Specifically, we observed that PQ401 not only induced cellular apoptosis in U87MG cells and subsequently reduced cell viability and proliferation but also attenuated cell mobility in vitro. More importantly, through a mouse xenograft model, we observed that administration of PQ401 on mice led to suppression of glioma tumour growth in vivo. In summary, our study suggests that PQ401 may serve as a promising leading drug for treating glioma patients with elevated IGF-1R signalling.
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http://dx.doi.org/10.1179/1973947815Y.0000000026DOI Listing
January 2017

Effects of ulinastatin on cerebral oxygen metabolism and CRP levels in patients with severe traumatic brain injury.

Exp Ther Med 2014 Jun 4;7(6):1683-1686. Epub 2014 Apr 4.

Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.

The aim of the present study was to investigate the effects of ulinastatin on cerebral oxygen metabolism and C-reactive protein (CRP) levels in patients with severe traumatic brain injury (sTBI). A total of 92 patients with sTBI, admitted to the First Affiliated Hospital of Xinxiang Medical University (Xinxiang, China), were randomly divided into control and observation groups. The control group received conventional therapy plus a placebo (0.9% sodium chloride), while the observation group were administered conventional therapy plus 200,000 units ulinastatin via intravenous injection twice a day for seven days. Arterial and jugular venous blood was collected for blood gas analysis. The jugular venous blood lactate (JVBL), jugular venous bulb oxygen saturation (SjvO), arteriovenous oxygen content difference (AVDO) and cerebral extraction of oxygen (CEO) levels were measured on day 1, 3, 5 and 7, as well as the level of CRP in the peripheral blood. In the control group, the level of JVBL decreased as compared with the level at day 1, however, no statistically significant differences were observed (P>0.05). By contrast, the observation group exhibited a significant reduction in the level of JVBL (P<0.05), which was also significantly lower compared with the control group (P<0.05). Statistically significant differences were observed between the two groups with regard to SjvO, AVDO and CEO on day 3, 5 and 7. The CRP levels in the two groups increased and peaked on day 3. However, the CRP level in the observation group significantly decreased on day 5 (35.27±15.18 mg/l) and day 7 (22.65±10.48 mg/l), which was lower compared with the control group (56.19±13.24 mg/l and 47.36±15.73 mg/l, respectively); statistically significant differences were observed (P<0.05). Therefore, ulinastatin effectively improved cerebral oxygen metabolism and reduced the CRP level in patients with sTBI.
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http://dx.doi.org/10.3892/etm.2014.1666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4043583PMC
June 2014

GDNF is involved in the barrier-inducing effect of enteric glial cells on intestinal epithelial cells under acute ischemia reperfusion stimulation.

Mol Neurobiol 2014 Oct 31;50(2):274-89. Epub 2014 May 31.

Department of General Surgery, Xinqiao Hospital, The Third Military Medical University, Chongqing, China, 400037.

Acute intestinal ischemia reperfusion (IR) injury is often associated with intestinal epithelial barrier (IEB) dysfunction. Enteric glial cells (EGCs) play an essential role in maintaining the integrity of IEB functions. However, the precise mechanism of EGCs under IR stimulation remains unclear. Here, we report that EGCs are closely involved in the modulation of IEB functions in response to IR challenge. The intestinal IR treatment led to the significant upregulation of the EGC activation marker, glial fibrillary acidic protein, accompanied by the increasing abundance of glial-derived neurotrophic factor (GDNF) and inducible nitric oxidase (iNOS) proteins, which was also confirmed in in vitro hypoxia reoxygenation (HR) tests. Co-culturing with EGCs attenuated the tight junctional abnormalities, blocked the downregulation of ZO-1 and occludin protein expression, and relieved the decrease of permeability of intestinal epithelial cell (IEC) monolayers under HR treatment. Furthermore, exogenous GDNF administration displays the barrier-protective effects similar to EGCs against HR stimulation, while RNA interference-mediated knockdown of GDNF significantly inhibited the protective capability of EGCs. The expression of both GDNF and iNOS proteins of EGCs was significantly upregulated by co-culturing with IECs, which was further increased by HR treatment. Interestingly, through inhibiting iNOS activity, the barrier-protective effect of EGCs was influenced in normal condition but enhanced in HR condition. These results suggest that GDNF plays an important role in the barrier-protective mechanism of activated EGCs under IR stimulation, whereas EGCs (via iNOS release) are also involved in intestinal inflammation response, which may contribute to IEB damage induced by IR injury.
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http://dx.doi.org/10.1007/s12035-014-8730-9DOI Listing
October 2014

Association of single-nucleotide polymorphisms in ERCC1 and ERCC2 with glioma risk.

Tumour Biol 2014 Aug 1;35(8):7451-7. Epub 2014 May 1.

Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, Henan, China,

We conducted a case-control study to assess the role of three single-nucleotide polymorphisms (SNPs) in excision repair cross-complementation group 1 (ERCC1) and two SNPs in excision repair cross-complementation group 2 (ERCC2) on the glioma risk in a Chinese population, and investigate the gene-environmental interaction for the cancer risk. A 1:2 matched case-control study was conducted. Logistic regression analysis revealed that individuals carrying ERCC1 rs2298881 CC genotype were associated with risk of glioma when compared with AA genotype carriers. The significant associations of ERCC1 rs2298881 polymorphism with glioma susceptibility were observed in both the dominant and the recessive models. In a stratification analysis, we found that ERCC1 rs2298881 variants showed an increased association with the risk of glioma in males, ever smokers, and high-grade glioma cases. In conclusion, our study suggests that ERCC1 rs2298881 polymorphism is associated with risk of glioma in codominant, dominant, and recessive models, especially in males, smokers, and high-grade glioma cases. This finding could be useful in revealing the genetic characteristics of glioma and suggests more effective strategies for prevention and treatment.
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http://dx.doi.org/10.1007/s13277-014-1969-yDOI Listing
August 2014

Involvement of miR-20a in promoting gastric cancer progression by targeting early growth response 2 (EGR2).

Int J Mol Sci 2013 Aug 6;14(8):16226-39. Epub 2013 Aug 6.

Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Xinqiao Road, Chongqing 400037, China.

Gastric cancer (GC) is one of the most common cancers, with high incidences in East Asia. microRNAs (miRNAs) play essential roles in the carcinogenesis of GC. miR-20a was elevated in GC, while the potential function of miR-20a was poorly understood. miR-20a expression was examined in GC tissues and cell lines. The effects of miR-20a on the growth, migration, invasion, and chemoresistance of GC cells were examined. Luciferase reporter assay and Western blot were used to screen the target of miR-20a. miR-20a was increased in GC tissues and cell lines. miR-20a promoted the growth, migration and invasion of GC cells, enhanced the chemoresistance of GC cells to cisplatin and docetaxel. Luciferase activity and Western blot confirmed that miR-20a negatively regulated EGR2 expression. Overexpression of EGR2 significantly attenuated the oncogenic effect of miR-20a. miR-20a was involved in the carcinogenesis of GC through modulation of the EGR2 signaling pathway.
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http://dx.doi.org/10.3390/ijms140816226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759908PMC
August 2013

Low concentrations of metformin selectively inhibit CD133⁺ cell proliferation in pancreatic cancer and have anticancer action.

PLoS One 2013 8;8(5):e63969. Epub 2013 May 8.

Pancreatic Disease Institute, Department of General Surgery, Union Hospital, HUST, Wuhan, P. R. China.

Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States. The prognosis remains dismal with little advance in treatment. Metformin is a drug widely used for the treatment of type II diabetes. Recent epidemiologic data revealed that oral administration of metformin is associated with a reduced risk of pancreatic cancer, suggesting its potential as a novel drug for this disease. Many studies have demonstrated the in vitro anticancer action of metformin, but the typically used concentrations were much higher than the in vivo plasma and tissue concentrations achieved with recommended therapeutic doses of metformin, and low concentrations of metformin had little effect on the proliferation of pancreatic cancer cells. We examined the effect of low concentrations of metformin on different subpopulations of pancreatic cancer cells and found that these selectively inhibited the proliferation of CD133⁺ but not CD24⁺CD44⁺ESA⁺ cells. We also examined the effect of low concentrations of metformin on cell invasion and in vivo tumor formation, demonstrating in vitro and in vivo anticancer action. Metformin was associated with a reduction of phospho-Erk and phospho-mTOR independent of Akt and AMPK phosphorylation. CD133⁺ pancreatic cancer cells are considered to be cancer stem cells that contribute to recurrence, metastasis and resistance to adjuvant therapies in pancreatic cancer. Our results provide a basis for combination of metformin with current therapies to improve the prognosis of this disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0063969PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648476PMC
December 2013

Three female familial cases of solid pseudopapillary tumors with a protease serine 1 gene mutation.

Pancreas 2013 Jan;42(1):168-73

Pancreatic Disease Institute, Department of General Surgery, Union Hospital, HUST, Wuhan, Hubei, China.

Solid pseudopapillary tumors (SPTs) are a rare pancreatic neoplastic lesion. Familial aggregation has not been reported in this disease. The objectives of this study were to report the history, clinicopathological features, and gene mutations of 3 familial cases of SPT. Three female cases of SPT presented in 1 family. Eight family relatives, 5 healthy volunteers, and 8 patients with SPT acted as controls. Histological examination and immunohistochemistry were performed on the surgical tumor specimens. Polymerase chain reaction-single-strand conformation polymorphism and gene sequencing were performed on genomic DNA extracted from blood. All 3 patients underwent surgical treatment, 2 patients died (3 months and 5 months after surgery), whereas neither recurrence nor metastasis was observed in the other patient during 2-year follow-up. The tumors from the 3 cases had identical immunoreactivity to a series of molecular markers. A Leu104Val mutation of protease serine 1 (PRSS1) was observed in the familial patients and 2 healthy male family members; no β-catenin or adenomatous polyposis coli mutations were detected in the familial cases. This study indicates the possibility of genetic involvement in the pathogenesis of SPT. Family history may be a positive predictive factor for malignancy in SPT.
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http://dx.doi.org/10.1097/MPA.0b013e3182554276DOI Listing
January 2013

Pancreatic ductal cells acquire mesenchymal characteristics through cell fusion with bone marrow-derived mesenchymal stem cells and SIRT1 attenuates the apoptosis of hybrid cells.

Cells Tissues Organs 2012 24;196(2):129-36. Epub 2012 Jan 24.

Pancreatic Disease Institute, Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Bone marrow-derived mesenchymal stem cells (bMSCs) contribute to tissue repair and regeneration. Cell fusion between somatic cells and bMSCs to form hybrid cells may have an important role in tissue repair through the subsequent reprogramming of the somatic cell nucleus. Few studies have assessed the mesenchymal characteristics of fusion-induced hybrid cells and their survival mechanisms. In this study, we investigated the effect of cell fusion on the biological characteristics of pancreatic ductal cells (PDCs) and on the survival mechanism of hybrid cells. To this end, we generated mouse-mouse hybrid cells in vitro by polyethylene glycol-mediated fusion of primary mouse bMSCs with primary mouse PDCs. Hybrid cells showed an enhanced capacity for proliferation and self-renewal compared with PDCs. No PDC had the capacity for anchorage-independent growth or invasion into Matrigel, but some hybrid cells were able to form colonies in soft agar and invade Matrigel. Expression of the tumor suppressor protein p53, which initiates apoptosis, was detected in hybrid cells but not in PDCs or bMSCs. However, the p53 deacetylase, sirtuin 1 (SIRT1), was also detected in hybrid cells, and the level of acetylated p53, the active form, was low. The addition of nicotinamide (Nam) inhibited the deacetylation activity of SIRT1 on p53 and induced cell apoptosis in hybrid cells. This study demonstrated that PDCs could obtain high proliferation rates, self-renewal capabilities, and mesenchymal characteristics by fusion with bMSCs. SIRT1 expression in the hybrid cells attenuated their apoptosis.
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http://dx.doi.org/10.1159/000332988DOI Listing
January 2013