Publications by authors named "Xiaojing Cheng"

52 Publications

Prevalence of mental disorders in 21st century Shandong Province, China: A ten-year comparative study.

J Affect Disord 2021 Feb 2;283:344-353. Epub 2021 Feb 2.

Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Road, Lixia district, Jinan, 250012 China; Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, China. Electronic address:

Background: Although the 2000s observed enormous changes in China, little is known about the variation in the prevalence of mental disorders. The study compared the prevalence in a Chinese population between 2004 and 2015.

Methods: Multistage stratified random sampling methods were used to identify primary sampling sites for cross-sectional surveys in 2004 and 2015 in Shandong, China. In 2004 and 2015, 22,718 and 28,194 adults, respectively, completed an expanded version of the General Health Questionnaire, then 5,402 and 9,420 adults, respectively, were administered a Chinese version of the Structured Clinical Interview for Diagnostic and Statistical Manual-IV axis I disorders.

Results: The adjusted 1-month prevalence of any mental disorders was 18•7% (95% CI: 16•7-20•8) and 17•1% (95% CI:15•9-18•4) in 2004 and 2015, respectively. However, the prevalence of major depressive disorders increased from 1•5% (95% CI: 1•2 -1•8) in 2004 to 2•3% (95% CI: 1•9-2•8) in 2015; meanwhile the prevalence of alcohol abuse disorders were becoming more common among men and urban residents. Although mood and anxiety disorders were more prevalent in women, a much more prevalent alcohol abuse disorders for men contributed to a higher overall prevalence among men than among women. Compared to that in urban residents, the overall prevalence in rural residents declined more, and it was lower in 2015 than in 2004.

Limitations: The results may not apply to the population from other regions.

Conclusions: Despite of the stable overall prevalence, mental disorders beyond psychotic disorders should be focused on, especially alcohol abuse and major depressive disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2021.01.068DOI Listing
February 2021

Sleep quality as a mediator of the association between coping styles and mental health: a population-based ten-year comparative study in a Chinese population.

J Affect Disord 2021 Jan 27;283:147-155. Epub 2021 Jan 27.

Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China; Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, China.

Backgrounds: Little is known about the variation in sleep quality and its association with coping style and mental health in 21 century China, despite of enormous socioeconomic changes. This study aims to document the variation in sleep quality and its contribution to the association between coping style and mental health in China.

Methods: Pooled cross-sectional data of 46,561 adults was obtained from the 2004 and 2015 mental health surveys conducted in Shandong Province, China. A Simplified Coping Style Questionnaire and the Pittsburgh Sleep Quality Index were assessed, with mental health measured by the General Health Questionnaire (GHQ). A mediation regression model was run to test the mediating effect of sleep quality.

Results: Above 10% reported poor sleep quality or median-to-high risk of mental disorders according to GHQ results in year 2015, and a significant but small improvement for sleep quality and mental health came during the studied decade, with the exception of poor sleep quality increasing among males. In 2015, a one-point increase in sleep quality score was associated with an increase of 0.17 (95% CI, 0.16-0.18) and 0.16 (95% CI, 0.14-0.17) points on the GHQ for males and females, respectively. Sleep quality mediated the relationship between negative tendency of coping style and elevated GHQ scores, and the mediating effects grew stronger in 2015 than those in 2004.

Limitation: The study is a cross-sectional study, and the sample is not nationally representative.

Conclusion: An integrative intervention of mental health promotion is recommended to account for sleep quality and coping strategies..
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2021.01.045DOI Listing
January 2021

The Developmental and Translational Study on Biomarkers and Clinical Characteristics-based Diagnostic and Therapeutic Identification of Major Depressive Disorder: Study Protocol for a Multicenter Randomized Controlled Trial in China.

Neuropsychiatr Dis Treat 2020 9;16:2343-2351. Epub 2020 Oct 9.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Background: Major depressive disorder (MDD) is a heterogeneous mental disease that encompasses different subtypes and specifiers. Clinically targeted treatments have not been identified yet, although standardized strategies are recommended by several clinical guidelines. The main aim of this study is to respectively identify the precise treatment for three different subtypes of MDD (ie, melancholic, atypical, and anxious).

Methods: An 8-to-12-week, multicenter randomized controlled trial (RCT) with a parallel group design will be conducted to determine the most effective and appropriate treatment. A total of 750 adults diagnosed with MDD will be recruited, categorized into melancholic, atypical or anxious type based on the assessment of the Inventory of Depressive Symptomatology (IDS30) and the Hamilton Anxiety Scale (HAMA), and 1:1 randomly assigned to different intervention groups. Blood draw, EEG test, and MRI scan will be performed at baseline and endpoint. Clinical symptom and side-effects will be evaluated at critical decision points (CDP) including weeks two, four, six, eight, and 12 after treatment. The primary outcome is total score and reduction rate of the 17-Hamilton Depression Rating Scale (17-HDRS). The secondary outcomes include the scores of the Quick Inventory of Depressive Symptomatology-self-report (QIDS-SR), IDS30, HAMA and the Treatment Emergent Symptom Scale (TESS). All the data will be analyzed by SAS software.

Discussion: The study commenced recruitment in August 2017 and is currently ongoing.

Trial Registration: ClinicalTrials.gov Identifier: NCT03219008 (July 17, 2017).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/NDT.S271842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553657PMC
October 2020

An integrated classifier improves prognostic accuracy in non-metastatic gastric cancer.

Oncoimmunology 2020 08 30;9(1):1792038. Epub 2020 Aug 30.

Department of Gastrointestinal Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.

The American Joint Committee on Cancer (AJCC) staging system is insufficiently prognostic for gastric cancer (GC) patients and complementary factors are in urgent need. Here we aimed to develop a comprehensive model, consisting of both immune signatures and cancer signaling molecules, which was expected to accurately improve survival prediction in non-metastatic gastric cancer (GC). We first validated the prognostic value of a combination of 18 immune features and 52 cancer-signaling molecules in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Then, their expression and distribution were analyzed in consecutive 1180 GC patients using immunohistochemistry. We developed and validated a novel protein-based prognostic classifier using CDH1, an epithelial-mesenchymal transition (EMT) marker, and five immune features (CD3, CD4, CD274, GZMB, and PAX5) by Cox regression model with group LASSO penalty. We observed significant differences in the overall survival of the high- and low-prognostic risk groups (66.8% VS 27.0%, < .001). A combination of this classifier with age and pTNM stage had better prognostic value than pTNM alone. The model was further validated in both treatment-naive patients and those treated with neoadjuvant chemotherapy. Moreover, GC patients with high-risk score exhibited a favorable prognosis to adjuvant chemotherapy. This integrated classifier could be automatically analyzed and effectively predict survival of GC patients and may provide a new clinically applicable strategy to identify patients who are more likely to benefit from adjuvant chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/2162402X.2020.1792038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470183PMC
August 2020

Brain transforms natural killer cells that exacerbate brain edema after intracerebral hemorrhage.

J Exp Med 2020 Dec;217(12)

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.

Perihematomal edema (PHE) occurs within hours after intracerebral hemorrhage (ICH), leading to secondary injury manifested by impaired blood-brain barrier (BBB) integrity and destruction of adjacent tissue. To dissect the mechanisms underlying PHE formation, we profiled human and mouse perihematomal tissues and identified natural killer (NK) cells as the predominant immune cell subset that outnumbers other infiltrating immune cell types during early stages of ICH. Unbiased clustering of single-cell transcriptional profiles revealed two major NK cell subsets that respectively possess high cytotoxicity or robust chemokine production features in the brain after ICH, distinguishing them from NK cells of the periphery. NK cells exacerbate BBB disruption and brain edema after ICH via cytotoxicity toward cerebral endothelial cells and recruitment of neutrophils that augment focal inflammation. Thus, brain-bound NK cells acquire new features that contribute to PHE formation and neurological deterioration following ICH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1084/jem.20200213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526480PMC
December 2020

Dyslipidemic Diet Induces Mobilization of Peripheral Neutrophils and Monocytes That Exacerbate Hemorrhagic Brain Injury and Neuroinflammation.

Front Cell Neurosci 2020 8;14:154. Epub 2020 Jun 8.

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.

: Non-alcoholic fatty liver disease (NAFLD) is a common liver condition characterized by a significant accumulation of lipids in the liver without excessive alcohol consumption. Accumulating evidence suggests a significantly increased risk of intracerebral hemorrhage (ICH) in NAFLD patients. However, it remains poorly understood whether and how NAFLD affects the outcome of hemorrhagic brain injury. Here, we examined the effects of diet-induce NAFLD on ICH injury and neuroinflammation in mice. : NAFLD was induced in C57BL/6 mice by feeding with a methionine-choline deficient (MCD) diet for 4 weeks. Collagenase and autologous blood models were used to evaluate the effects of NAFLD on ICH injury and neuroinflammation. : MCD diet for 4 weeks induces NAFLD and hyperlipidemia in mice. Mice receiving the MCD diet have aggravated neurological deficits and brain edema after ICH. The augmentation of ICH injury was accompanied by brain infiltration of neutrophils and monocytes and increased production of pro-inflammatory factors. Before ICH, MCD diet-induced mobilization of neutrophils and monocytes in the periphery. Notably, the detrimental effects of NAFLD on ICH injury was ablated in mice receiving antibody depletion of neutrophils and monocytes. : These results suggest that NAFLD exacerbates neuroinflammation and ICH injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fncel.2020.00154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325918PMC
June 2020

Brain Ischemia Significantly Alters microRNA Expression in Human Peripheral Blood Natural Killer Cells.

Front Immunol 2020 14;11:759. Epub 2020 May 14.

Department of Imaging, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Brain ischemia induces systemic immunosuppression and increases a host's susceptibility to infection. MicroRNAs (miRNAs) are molecular switches in immune cells, but the alterations of miRNAs in human immune cells in response to brain ischemia and their impact on immune defense remain elusive. Natural killer (NK) cells are critical for early host defenses against pathogens. In this study, we identified reduced counts, cytokine production, and cytotoxicity in human peripheral blood NK cells obtained from patients with acute ischemic stroke. The extent of NK cell loss of number and activity was associated with infarct volume. MicroRNA sequencing analysis revealed that brain ischemia significantly altered miRNA expression profiles in circulating NK cells, in which miRNA-451a and miRNA-122-5p were dramatically upregulated. Importantly, inhibition of miR-451a or miR-122-5p augmented the expression of activation-associated receptors in NK cells. These results provide the first evidence that brain ischemia alters miRNA signatures in human NK cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.00759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240012PMC
May 2020

Improving the High-Current-Density Performance of PEMFC through Much Enhanced Utilization of Platinum Electrocatalysts on Carbon.

ACS Appl Mater Interfaces 2020 Jun 1;12(23):26076-26083. Epub 2020 Jun 1.

Institute of Fuel Cells, MOE Key Laboratory of Power Machinery & Engineering, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.

We report an effective approach to the synthesis of high-content and high-dispersion Pt nanoparticles (NPs) on XC-72 carbon black as a cathode electrocatalyst with improved high-current-density performance in proton exchange membrane fuel cells (PEMFCs). While exceptionally high catalytic activity for oxygen reduction reaction (ORR) was reported based on the rotating disk electrode (RDE) technique, such catalysts do not deliver nearly the same level of performance in PEMFC due to the lack of optimized design of catalyst structures on carbon support. We recently developed a synergistic synthesis method to make exceptionally high-content and finely dispersed Pt catalysts, which showed the highest Pt-electroactive surface area and the highest Pt mass activity for ORR among the electrocatalysts tested. More importantly, the membrane electrode assembly (MEA) made with this catalyst showed excellent performance at current densities higher than 1200 mA cm in a hydrogen-air PEMFC measurement. Pt NMR was used to analyze the molecular structures of the metal precursors and to understand the mechanisms of the formation of Pt catalysts at high dispersity and uniformity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c06981DOI Listing
June 2020

TNFRSF11B activates Wnt/β-catenin signaling and promotes gastric cancer progression.

Int J Biol Sci 2020 25;16(11):1956-1971. Epub 2020 Apr 25.

Key laboratory of Carcinogenesis and Translational Research (Ministry of education), Division of gastrointestinal Cancer Translational Research laboratory, Peking University Cancer Hospital & Institute, Beijing, China.

Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) has been studied to be involved in the development and progression of several human malignancies. However, little is unveiled regarding the complex mechanisms of TNFRSF11B in human gastric cancer (GC). The clinical significance of TNFRSF11B was assessed in 70 and 160 GC tissues using immunohistochemistry method and gene microarray analysis, respectively. The biological function of TNFRSF11B was studied in vitro and in vivo assays. Immunofluorescence assay was used to evaluate the expression of β-catenin in the nucleus. The expression of β-catenin and related protein was determined by Western blot. The interaction between TNFRSF11B and GSK3β was detected by co-immunoprecipitation. We demonstrated that TNFRSF11B was highly expressed in the cytoplasm of GC and associated with the patient poor outcome. Our studies showed that TNFRSF11B in GC cells significantly promoted cell proliferation, migration, invasion and tumorigenic ability and . Meanwhile, TNFRSF11B inhibited GC cell apoptosis. The proportion of nuclear active β-catenin showed positively correlation with TNFRSF11B expression. TNFRSF11B directly combined with GSK-3β upregulating its phosphorylation, and increased expression of β-catenin and its downstream effectors. Collectively, these findings demonstrate that TNFRSF11B promote the aggressive phenotypes of GC cells and activated Wnt/β-catenin signaling. Accordingly, TNFRSF11B had potential as a biomarker and inhibition of TNFRSF11B expression might offer a new therapeutic target for GC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijbs.43630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211174PMC
April 2020

Erratum: Intensified Stiffness and Photodynamic Provocation in a Collagen-Based Composite Hydrogel Drive Chondrogenesis.

Adv Sci (Weinh) 2020 03 18;7(6):2000588. Epub 2020 Mar 18.

[This corrects the article DOI: 10.1002/advs.201900099.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/advs.202000588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080505PMC
March 2020

TfR1 binding with H-ferritin nanocarrier achieves prognostic diagnosis and enhances the therapeutic efficacy in clinical gastric cancer.

Cell Death Dis 2020 02 5;11(2):92. Epub 2020 Feb 5.

Key Laboratory Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China.

H-ferritin (HFn) nanocarrier is emerging as a promising theranostic platform for tumor diagnosis and therapy, which can specifically target tumor cells via binding transferrin receptor 1 (TfR1). This led us to investigate the therapeutic function of TfR1 in GC. The clinical significance of TfR1 was assessed in 178 GC tissues by using a magneto-HFn nanoparticle-based immunohistochemistry method. The therapeutic effects of doxorubicin-loaded HFn nanocarriers (HFn-Dox) were evaluated on TfR1-positive GC patient-derived xenograft (GC-PDX) models. The biological function of TfR1 was investigated through in vitro and in vivo assays. TfR1 was upregulated (73.03%) in GC tissues, and reversely correlated with patient outcome. TfR1-negative sorted cells exhibited tumor-initiating features, which enhanced tumor formation and migration/invasion, whereas TfR1-positive sorted cells showed significant proliferation ability. Knockout of TfR1 in GC cells also enhanced cell invasion. TfR1-deficient cells displayed immune escape by upregulating PD-L1, CXCL9, and CXCL10, when disposed with IFN-γ. Western blot results demonstrated that TfR1-knockout GC cells upregulated Akt and STAT3 signaling. Moreover, in TfR1-positive GC-PDX models, the HFn-Dox group significantly inhibited tumor growth, and increased mouse survival, compared with that of free-Dox group. TfR1 could be a potential prognostic and therapeutic biomarker for GC: (i) TfR1 reversely correlated with patient outcome, and its negative cells possessed tumor-aggressive features; (ii) TfR1-positive cells can be killed by HFn drug nanocarrier. Given the heterogeneity of GC, HFn drug nanocarrier combined with other therapies toward TfR1-negative cells (such as small molecules or immunotherapy) will be a new option for GC treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-020-2272-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002446PMC
February 2020

Increased expression of Psoriasin is correlated with poor prognosis of bladder transitional cell carcinoma by promoting invasion and proliferation.

Oncol Rep 2020 Feb 24;43(2):562-570. Epub 2019 Dec 24.

Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.

Psoriasin, otherwise known as S100A7, is a member of the S100 protein family. With the key function of binding calcium, it is able to regulate a range of cellular functions. Altered Psoriasin expression is associated with poor clinical outcomes in several solid cancers. The present study aimed to examine the implication of Psoriasin in bladder cancer (BC). Expression of Psoriasin was examined in BC cell lines using PCR. Immunohistochemical (IHC) staining of Psoriasin was performed on a bladder disease spectrum tissue array. Plasmids were constructed to effectively knockdown and overexpress Psoriasin in BC cells and further utilized for in vitro BC cellular function assays. Association between Psoriasin expression and survival of patients with BC was evaluated using Kaplan‑Meier survival analysis. Psoriasin was revealed to be expressed by both bladder epithelia and cancer cells as determined by IHC. Increased expression of Psoriasin was significantly correlated with a poor overall BC patient survival. Overexpression of Psoriasin in the EJ138 cell line increased cellular proliferation, adhesion and invasion, whereas knockdown exhibited the opposite effect on cellular functions in RT112 cells. Matrix metalloprotease (MMP)9 appeared to be the most affected of the three MMPs examined in these two BC cell lines. The analysis revealed a positive correlation in BC tumours between Psoriasin and MMP9. Overall, high Psoriasin expression was correlated with poor overall survival in BC patients and promoted invasiveness of BC cells via upregulation of MMPs. Psoriasin possesses certain prognostic and therapeutic potential in BC which requires further exploration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/or.2019.7445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6967103PMC
February 2020

Epithelial Cell Adhesion Molecule in Primary Sjögren's Syndrome Patients: Characterization and Evaluation of a Potential Biomarker.

J Immunol Res 2019 5;2019:3269475. Epub 2019 Dec 5.

Department of Clinical Immunology, Xijing Hospital, Air Force Medical University (Fourth Military Medical University), China.

Objective: To determine the subcellular localization of epithelial cell adhesion molecule (EpCAM) in labial salivary gland (LSG) and evaluate the diagnostic use of the extracellular domain of EpCAM (EpEX) and intracellular domain (EpICD) for primary Sjögren's syndrome (pSS).

Methods: Immunohistochemical (IHC) analysis was conducted using EpEX and EpICD domain-specific antibodies on labial salivary gland biopsy (LSGB) from participants. Chi-square or Fisher's exact analysis, Mann-Whitney -test, and Kruskal-Wallis test compared differences among groups. Independent risk factors of pSS were determined by multiple logistic regression analysis. Receiver-operator characteristic curves (ROC) were carried out to estimate the diagnostic value.

Results: Compared to non-SS controls, loss of membranous EpEX and EpICD expression was observed in LSGB of pSS patients, which occurred in parallel with increased accumulation of cytoplastic and nuclear EpICD. The subcellular EpEX/EpICD expressions were associated with various features of pSS patients, especially histopathological grade of LSGB. Furthermore, high IHC scores of membranous EpEX were independent risk factors for pSS, even for the pSS patients at early stage. The IHC scores of subcellular EpEX/EpICD were of great diagnostic value for pSS with high sensitivity (70-80%) and specificity (85-95%).

Conclusion: This study first found the aberrant expression pattern of EpCAM in LSG of pSS patients. The IHC scores of subcellular EpEX/EpICD were demonstrated to have the potential to act as diagnostic biomarkers for pSS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/3269475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915146PMC
May 2020

HOXB2 is a Putative Tumour Promotor in Human Bladder Cancer.

Anticancer Res 2019 Dec;39(12):6915-6921

Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, U.K.

Background/aim: The present study aimed to investigate the role of Homebox B2 (HOXB2) in bladder cancer (BC).

Materials And Methods: The Cancer Genome Atlas (TCGA) dataset was used to analyse HOXB2 expression in BC. The influence of HOXB2 on the cellular functions of BC cells was determined in both HOXB2 knockdown and HOXB2 overexpressed BC cell lines using in vitro assays.

Results: HOXB2 mRNA was significantly upregulated in luminal infiltrated and luminal papillary subtypes of BC. Drug Metabolism Cytochrome P450 was significantly enriched in BCs expressing high levels of HOXB2. Knockdown of HOXB2 from EJ138 cells reduced growth, adhesion and invasion. In contrast, overexpression of HOXB2 in RT112 cells induced growth and adhesion of bladder cancer cells.

Conclusion: Increased HOXB2 expression in papillary BC can promote cell growth and adhesion of BC cells. Drug Metabolism Cytochrome P450 pathway was enriched in BCs overexpressing HOXB2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.13912DOI Listing
December 2019

EIF3B is associated with poor outcomes in gastric cancer patients and promotes cancer progression via the PI3K/AKT/mTOR signaling pathway.

Cancer Manag Res 2019 21;11:7877-7891. Epub 2019 Aug 21.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.

Purpose: Eukaryotic translation initiation factor (EIF) plays a vital role in protein synthesis. EIF3B is a core subunit of the EIF3 family, and is overexpressed in many tumors. EIF3B is associated with an unfavorable prognosis, as well as the genesis and development of tumors. However, the potential role of EIF3B in gastric cancer (GC) remains unknown. In the current study, we explored the clinical significance and the possible mechanism of EIF3B in the progression of GC.

Methods: EIF3B expression was analyzed in 78 GC tissue samples through quantitative PCR and in 94 GC tissue samples through immunohistochemistry (IHC) staining. The correlation between EIF3B and clinicopathological features was analyzed in GC tissues. The role of EIF3B in GC progression was investigated through in vitro and in vivo assays.

Results: EIF3B expression was upregulated in GC tissues (73.4%, IHC). High expression of EIF3B was significantly correlated with the depth of tumor invasion, lymph node metastasis and TNM stage (=0.000, 0.000 and 0.000, respectively). Multivariate analysis indicated that GC patients with high EIF3B expression suffered a poorer 5-year survival. EIF3B promoted GC cell proliferation and was strongly associated with proliferating cell nuclear antigen (PCNA) expression in GC samples (=0.009). It also enhanced tumor cell migration and invasion, which were affected through epithelial-mesenchymal transition (EMT) and the Stat3 signaling pathway. Knockdown of EIF3B in GC cells suppressed the growth of xenograft tumors and lung metastatic colonization in vivo. Furthermore, gene set enrichment analysis (GSEA) and Western blot results demonstrated that EIF3B activated the PI3K/AKT/mTOR signaling pathway.

Conclusion: Our results suggest that EIF3B plays an oncogenic role in GC progression and serves as an independent prognostic factor for GC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S207834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708883PMC
August 2019

Intensified Stiffness and Photodynamic Provocation in a Collagen-Based Composite Hydrogel Drive Chondrogenesis.

Adv Sci (Weinh) 2019 Aug 15;6(16):1900099. Epub 2019 Jul 15.

Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration The First Affiliated Hospital of Guangxi Medical University No. 6 Shuangyong Road Nanning 530021 P. R. China.

Directed differentiation of bone-marrow-derived stem cells (BMSCs) toward chondrogenesis has served as a predominant method for cartilage repair but suffers from poor oriented differentiation tendency and low differentiation efficiency. To overcome these two obstacles, an injectable composite hydrogel that consists of collagen hydrogels serving as the scaffold support to accommodate BMSCs and cadmium selenide (CdSe) quantum dots (QDs) is constructed. The introduction of CdSe QDs considerably strengthens the stiffness of the collagen hydrogels via mutual crosslinking using a natural crosslinker (i.e., genipin), which simultaneously triggers photodynamic provocation (PDP) to produce reactive oxygen species (ROS). Experimental results demonstrate that the intensified stiffness and augmented ROS production can synergistically promote the proliferation of BMSCs, induce cartilage-specific gene expression and increase secretion of glycosaminoglycan. As a result, this approach can facilitate the directed differentiation of BMSCs toward chondrogenesis and accelerate cartilage regeneration in cartilage defect repair, which routes through activation of the TGF-β/SMAD and mTOR signaling pathways, respectively. Thus, this synergistic strategy based on increased stiffness and PDP-mediated ROS production provides a general and instructive approach for developing alternative materials applicable for cartilage repair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/advs.201900099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702628PMC
August 2019

A panel of DNA methylated markers predicts metastasis of pNM gastric carcinoma: a prospective cohort study.

Br J Cancer 2019 10 21;121(7):529-536. Epub 2019 Aug 21.

Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Fu-Cheng-Lu, No. 52, Haidian District, Beijing, 100142, China.

Background: The aim of this prospective study was to evaluate the feasibility of predicting GC metastasis using CDH1, GFRA1, P16 and ZNF382 DNA methylation as biomarkers.

Methods: 198 GC patients without metastasis at the time of surgery resection were recruited into the double-blind cohort (NCT02159339). Gene methylation was analysed using MethyLight assays. GC metastasis and survival data were obtained from 178 patients with 94.7% compliance during follow-up.

Results: Twenty six cases of metastasis and 5 cases of recurrence were observed in 178 cases (17.4%) during the follow-up (median, 62.7 months). The GC metastasis rate for GFRA1 methylation-positive patients was significantly reduced compared with GFRA1 methylation-negative patients (odds ratio [OR]: 0.23, 95% confidence interval [CI] 0.08-0.66). Similar results were also observed using ZNF382 methylation as a predictor (OR: 0.17, 95% CI 0.06-0.47). A risk score including methylation of GFRA1 and ZNF382 was generated. The metastasis rate was significantly increased in high-risk GC patients (OR: 4.71, 95% CI: 1.85-12.00). GC patients with high risk had a shorter overall survival, especially for patients with stage I GC (P = 0.024).

Conclusions: The combination of GFRA1 and ZNF382 methylation is a biomarker panel for the prediction of GC metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41416-019-0552-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889426PMC
October 2019

Downregulation of TfR1 promotes progression of colorectal cancer via the JAK/STAT pathway.

Cancer Manag Res 2019 9;11:6323-6341. Epub 2019 Jul 9.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, People's Republic of China.

Colorectal cancer (CRC) is one of the most prevalent gastrointestinal malignancies. The incidence of CRC has been rapidly increasing in China. Transferrin receptor 1 (TfR1) is a key regulator of cellular iron homeostasis. Several studies have demonstrated TfR1 overexpression in a variety of human tumors, but the association between TfR1 and CRC remains unclear. TfR1 expression was evaluated in six CRC cell lines and tumor tissues. A total of 201 CRC patients were included for immunohistochemistry and 19 pairs of frozen tissues were used for real-time PCR. Cell proliferation, cell cycle, cell migration and invasion, and in vivo carcinogenesis were tested after downregulation of TfR1 by lentivirus. Protein microarray and Western blot analyses were used to explore the underlying mechanisms of TfR1 in CRC. TfR1 expression was higher in CRC tissues than in normal tissues (57.2% vs 22.9%, <0.001). TfR1 expression was obviously higher in CRC tissues with well differentiation (=0.008), no lymph node metastasis (=0.002), no distant metastasis (=0.006), no vascular invasion (<0.001) and early TNM stage (=0.013). CRC patients with TfR1-positive expression had a better survival than those with TfR1-negative expression (=0.044). Downregulation of TfR1 expression inhibited cell proliferation, promoted cells from G1 phase to S phase and facilitated cell migration and invasion. Knockdown of TfR1 also suppressed tumor growth in BALB/C-nu mice. Protein microarray and Western blot analyses showed that the Janus protein tyrosine kinase/signal transducer and activator of transcription pathway was activated along with downregulation of TfR1 expression. Though TfR1 was overexpressed in colorectal cancer tissues, there was evidence that downregulation of TfR1 could promote cancer progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S198911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628123PMC
July 2019

Inhibition of fibrin formation reduces neuroinflammation and improves long-term outcome after intracerebral hemorrhage.

Int Immunopharmacol 2019 Jul 28;72:473-478. Epub 2019 Apr 28.

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address:

Background: Intracerebral hemorrhage (ICH) is a severe type of stroke without effective treatment. The coagulation cascade is activated after blood flows into the brain parenchyma. The conversion of fibrinogen to fibrin is an essential step of coagulation processes, but its influences on neuroinflammation and long-term outcome after ICH have not been adequately studied. Hirudin binds to thrombin and inhibits the conversion of fibrinogen to fibrin. We therefore investigated the impact of hirudin treatment on brain inflammation and long-term outcome of ICH in mice.

Methods: Fibrinogen levels were measured in plasma samples from patients with ICH. In mice subjected to collagenase injection, fibrinogen levels were measured in the plasma and brain. The impact of hirudin on neuroinflammation and long-term neurological outcome was determined in ICH mice.

Results: Circulating fibrinogen level was increased in patients with ICH at day 1 and day 4 after onset. In ICH mice, fibrinogen levels in the blood and brain were increased at day 7. Delayed daily administration of hirudin from day 7 to day 28 significantly improved long-term outcome in ICH mice. Hirudin treatment reduced leukocyte accumulation in the brain and shifted microglia toward an anti-inflammatory phenotype. In addition, depletion of microglia in ICH mice diminished the benefit of hirudin in ICH mice.

Conclusions: These results suggest that inhibition of fibrin formation alleviates brain inflammation and improves long-term outcome after ICH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2019.04.029DOI Listing
July 2019

Depletion of death-associated protein-3 induces chemoresistance in gastric cancer cells through the β-catenin/LGR5/Bcl-2 axis.

J Investig Med 2019 06 20;67(5):856-861. Epub 2019 Feb 20.

Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.

Previously, we demonstrated that death-associated protein-3 (DAP3) loss drives chemoresistance in gastric cancer cells. In the present study, we aimed to determine the underlying molecular mechanism. The effect of DAP3 silencing on β-catenin signaling was assessed. The direct mediator of DAP3 silencing-induced chemoresistance was identified. Depletion of DAP3 stimulates nuclear accumulation of β-catenin and enhances β-catenin-dependent transcriptional activity in gastric cancer cells. However, the protein kinase B , , extracellular regulated protein kinase and signal transducer and activator of transcription 3 signaling pathways remain unaffected by DAP3 loss. We found that the downstream target gene LGR5 (leucine-rich G-protein coupled receptor 5) is upregulated in DAP3-depleted gastric cancer cells. Moreover, knockdown of LGR5 resensitizes DAP3-depleted gastric cancer cells to 5-fluorouracil (5-FU) and oxaliplatin. We also observed that ectopic expression of LGR5 reduces apoptosis in gastric cancer cells on treatment with 5-FU and oxaliplatin, which is accompanied by prevention of caspase-3 cleavage. The antiapoptotic protein Bcl-2 is identified as a key mediator of LGR5-induced apoptosis resistance in gastric cancer cells. The present findings indicate that DAP3 deficiency-induced chemoresistance in gastric cancer is at least partially mediated through the β-catenin/LGR5/Bcl-2 axis. Targeting LGR5 may provide a novel strategy to overcome chemoresistance in DAP3-deficient gastric cancer cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jim-2018-000934DOI Listing
June 2019

Analysis of PD1, PDL1, PDL2 expression and T cells infiltration in 1014 gastric cancer patients.

Oncoimmunology 2018;7(3):e1356144. Epub 2017 Dec 21.

Department of Gastrointestinal Translational Research, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.

Although immune checkpoint blockade have demonstrated promising results, their effects on gastric cancer (GC) are under investigation. Understanding the clinical significance of PD1 and its ligands' expression, together with T cell infiltration might provide clues for biomarkers screening in GC immunotherapy. Immunohistochemistry were performed on a tissue microarray including 1,014 GC specimens using PD1, PDL1 and PDL2 antibodies. T cell markers CD3 and CD8 were also stained and quantified by automated image analysis. Correlation with clinical features and outcome were analyzed after controlling for potential confounders including EBV infection, HER2, C-met and PCNA expression. 37.8% of the cases showed membranous PD-L1 expression in tumor cells and 74.9% in infiltrating immune cells. PDL1 expression rate was rather higher in patients without metastasis, in EBV positive group and those with C-met and PCNA expression. GC patients with high level PDL1 expression exhibited better survival. GC Patients with higher T cell infiltration also showed elevated PDL1, PDL2 and PD1 expression and predict favorable outcome, indicating an adaptive immune resistance mechanism may exist. The group of patients infiltrated with lower density CD3+ T cells also without PDL1 expression in tumor cells predict the worst outcome in the subgroup of different PTNM stage, which may suggest an inactive immune status. These results highlights the need to assess both PDL1 expression in all tumor context and the characterization of the GC immune microenvironment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/2162402X.2017.1356144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790386PMC
December 2017

Association between gene polymorphism and susceptibility to and prognosis of diffuse large B-cell lymphoma.

Oncol Lett 2018 Jan 1;15(1):264-270. Epub 2017 Nov 1.

Department of Lymphoma, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.

Lysosomal protein transmembrane 4β () is an oncogene that is overexpressed in a number of various types of human cancer. There are two known alleles of : and . The present study assessed the association between polymorphisms and the susceptibility to diffuse large B-cell lymphoma (DLBCL) and its prognosis. genotypes were determined using polymerase chain reaction analysis in 164 DLBCL and 350 healthy control cases. The association between polymorphisms and the risk of DLBCL was analyzed using unconditional logistic regression. Differences in patient survival were calculated using Kaplan-Meier analysis. The present study indicated no significant differences (P>0.05) in the frequency of alleles between DLBCL cases (26.5%) and controls (24.1%). The risk of DLBCL was slightly increased in cases with the genotype [odds ratio (OR)=1.160; 95% confidence interval (CI)=0.781-1.724] or the genotype (OR=1.446; 95% CI=0.648-3.227) compared with those with the genotype. There was no significant association between the presence of the allele and overall survival (OS) and disease-free survival (DFS) in patients with DLBCL (P=0.399 and 0.520, respectively). However, there was a tendency for patients with and International Prognostic Index (IPI) score 3-5 to have longer OS and DFS (P=0.126 and 0.109, respectively). These findings suggest that genetic polymorphisms of is not a risk factor for the development of DLBCL, but the allele may a better prognostic indicator in patients with IPI score 3-5 in DLBCL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2017.7318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768069PMC
January 2018

The Experimental Measurement of Local and Bulk Oxygen Transport Resistances in the Catalyst Layer of Proton Exchange Membrane Fuel Cells.

J Phys Chem Lett 2017 Dec 17;8(23):5848-5852. Epub 2017 Nov 17.

Institute of Fuel Cells, School of Mechanical Engineering, and ‡SJTU-ParisTech Elite Institute of Technology, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai, 200240, China.

Remarkable progress has been made in reducing the cathodic Pt loading of PEMFCs; however, a huge performance loss appears at high current densities, indicating the existence of a large oxygen transport resistance associated with the ultralow Pt loading catalyst layer. To reduce the Pt loading without sacrificing cell performance, it is essential to illuminate the oxygen transport mechanism in the catalyst layer. Toward this goal, an experimental approach to measure the oxygen transport resistance in catalyst layers is proposed and realized for the first time in this study. The measuring approach involves a dual-layer catalyst layer design, which consists of a dummy catalyst layer and a practical catalyst layer, followed by changing the thickness of dummy layer to respectively quantify the local and bulk resistances via limiting current measurements combined with linear extrapolation. The experimental results clearly reveal that the local resistance dominates the total resistance in the catalyst layer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpclett.7b02580DOI Listing
December 2017

Exploration of significant influences of the operating conditions on the local O transport in proton exchange membrane fuel cells (PEMFCs).

Phys Chem Chem Phys 2017 Oct;19(38):26221-26229

Institute of Fuel Cells, School of Mechanical Engineering, Shanghai Jiao Tong University, China.

A drastic reduction of the Pt loading in the cathode catalyst layers (CCLs) of proton exchange membrane fuel cells (PEMFCs) is much desired. However, a decrease in Pt loading inevitably leads to an unexpected increase of local O transport resistance (r) and severely weakens the fuel cell performance, particularly at high current densities. Thus, it is both urgent and meaningful to explore the impacts of the operating conditions on r in CCLs and therefore to clarify the intrinsic mechanism. Herein, we systematically explore the influences of the operating conditions, in terms of the dry O mole fraction, the relative humidity, the operating pressure and the temperature on r using limiting current measurements combined with mathematical calculations. The results show that, in contrary to the established rules, r in CCLs of PEMFCs is aggravated when the dry O mole fraction or the operating pressure are increased. It is also experimentally found that r in CCLs is alleviated with the increase in the relative humidity or the operating temperature. Moreover, an adsorption controlled solution-diffusion model is proposed to illuminate the local O transport behavior in CCLs of PEMFCs, and it accounts for the influence of the dry O mole fraction on r in CCLs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c7cp04837hDOI Listing
October 2017

Prognostic value of a 25-gene assay in patients with gastric cancer after curative resection.

Sci Rep 2017 08 8;7(1):7515. Epub 2017 Aug 8.

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Central Biobank Facility, Peking University Cancer Hospital and Institute, Beijing, China.

This study aimed to develop and validate a practical, reliable assay for prognosis and chemotherapy benefit prediction compared with conventional staging in Gastric cancer (GC). Twenty-three candidate genes with significant correlation between quantitative hybridization and microarray results plus 2 reference genes were selected to form a 25-gene prognostic classifier, which can classify patients into 3 distinct groups of different risk of mortality obtained by analyzing microarray data from 78 frozen tumor specimens. The 25-gene assay was associated with overall survival in both training (P = 0.017) and testing cohort (P = 0.005) (462 formalin-fixed paraffin-embedded samples). The risk prediction in stages I + II is significantly better than that in stages III. Analysis demonstrated that this 25-gene signature is an independent prognostic predictor and show higher prognostic accuracy than conventional TNM staging in early stage patients. Moreover, only high-risk patients in stage I + II were found benefit from adjuvant chemotherapy (P = 0.043), while low-risk patients in stage III were not found benefit from adjuvant chemotherapy. In conclusion, our results suggest that this 25-gene assay can reliably identify patients with different risk for mortality after surgery, especially for stage I + II patients, and might be able to predict patients who benefit from chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-07604-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548732PMC
August 2017

Baicalin inhibits biofilm formation, attenuates the quorum sensing-controlled virulence and enhances Pseudomonas aeruginosa clearance in a mouse peritoneal implant infection model.

PLoS One 2017 28;12(4):e0176883. Epub 2017 Apr 28.

Department of Respiratory Disease, First Affiliated Hospital of Guangxi Medical University, Qingxiu, Nanning, Guangxi, People's Republic of China.

The quorum sensing (QS) circuit plays a role in the precise regulation of genes controlling virulence factors and biofilm formation in Pseudomonas aeruginosa. QS-controlled biofilm formation by Pseudomonas aeruginosa in clinical settings has remained controversial due to emerging drug resistance; therefore, screening diverse compounds for anti-biofilm or anti-QS activities is important. This study demonstrates the ability of sub-minimum inhibitory concentrations (sub-MICs) of baicalin, an active natural compound extracted from the traditional Chinese medicinal Scutellaria baicalensis, to inhibit the formation of Pseudomonas aeruginosa biofilms and enhance the bactericidal effects of various conventional antibiotics in vitro. In addition, baicalin exerted dose-dependent inhibitory effects on virulence phenotypes (LasA protease, LasB elastase, pyocyanin, rhamnolipid, motilities and exotoxin A) regulated by QS in Pseudomonas aeruginosa. Moreover, the expression levels of QS-regulatory genes, including lasI, lasR, rhlI, rhlR, pqsR and pqsA, were repressed after sub-MIC baicalin treatment, resulting in significant decreases in the QS signaling molecules 3-oxo-C12-HSL and C4-HSL, confirming the ability of baicalin-mediated QS inhibition to alter gene and protein expression. In vivo experiments indicated that baicalin treatment reduces Pseudomonas aeruginosa pathogenicity in Caenorhabditis elegans. Greater worm survival in the baicalin-treated group manifested as an increase in the LT50 from 24 to 96 h. In a mouse peritoneal implant infection model, baicalin treatment enhanced the clearance of Pseudomonas aeruginosa from the implants of mice infected with Pseudomonas aeruginosa compared with the control group. Moreover, the combination of baicalin and antibiotics significantly reduced the numbers of colony-forming units in the implants to a significantly greater degree than antibiotic treatment alone. Pathological and histological analyses revealed mitigation of the inflammatory response and reduced cell infiltration in the peritoneal tissue surrounding the implants after baicalin treatment. Measurement of the cytokine levels in the peritoneal lavage fluid of mice in the baicalin treatment group revealed a decrease in IL-4, an increase in interferon γ (IFN-γ), and a reversed IFN-γ/IL-4 ratio compared with the control group, indicating that baicalin treatment activated the Th1-induced immune response to expedite bacterial load clearance. Based on these results, baicalin might be a potent QS inhibitor and anti-biofilm agent for combating Pseudomonas aeruginosa biofilm-related infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0176883PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409170PMC
September 2017

The respective effect of under-rib convection and pressure drop of flow fields on the performance of PEM fuel cells.

Sci Rep 2017 03 2;7:43447. Epub 2017 Mar 2.

Institute of Fuel Cell, School of Mechanical Engineering, Shanghai Jiao Tong University, Dongchuan Rd. 800, Shanghai, China.

The flow field configuration plays an important role on the performance of proton exchange membrane fuel cells (PEMFCs). For instance, channel/rib width and total channel cross-sectional area determine the under-rib convection and pressure drop respectively, both of which directly influence the water removal, in turn affecting the oxygen supply and cathodic oxygen reduction reaction. In this study, effects of under-rib convection and pressure drop on cell performance are investigated experimentally and numerically by adjusting the channel/rib width and channel cross-sectional area of flow fields. The results show that the performance differences with various flow field configurations mainly derive from the oxygen transport resistance which is determined by the water accumulation degree, and the cell performance would benefit from the narrower channels and smaller cross sections. It reveals that at low current densities when water starts to accumulate in GDL at under-rib regions, the under-rib convection plays a more important role in water removal than pressure drop does; in contrast, at high current densities when water starts to accumulate in channels, the pressure drop dominates the water removal to facilitate the oxygen transport to the catalyst layer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep43447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333141PMC
March 2017

Influence of Freeze-Thaw Cycles on RNA Integrity of Gastrointestinal Cancer and Matched Adjacent Tissues.

Biopreserv Biobank 2017 Jun 7;15(3):241-247. Epub 2017 Feb 7.

1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of BioBank, Peking University Cancer Hospital and Institute , Beijing, China .

Background: Comparative analysis of RNA expression profiles between cancer and adjacent noncancerous tissues is an important part of cancer research. High-quality RNA is essential for consistent, reliable results, especially for identification of cancer biomarkers. However, the impact of freeze-thaw cycles on the quality of RNA both in gastrointestinal cancer and paired adjacent tissues is still unclear.

Aim: To investigate the influence of freeze-thaw cycles on RNA integrity and overall histomorphology of gastrointestinal cancer and paired adjacent noncancerous tissues.

Methods: Gastrointestinal cancer and matched adjacent noncancerous tissues were frozen and thawed twice before extracting RNA. Total RNA in each sample was extracted with TRIzol reagents and the RNA integrity was assessed by RNA integrity number (RIN) on an Agilent Bioanalyzer. Light microscopy was then used to assess tissue composition and morphology.

Results: RIN values for all samples tended to decrease in correlation with the frequency of freeze-thawing. With an RIN cutoff value of 6, RNA extracted from pancreatic cancer tissues was not qualified after the first freeze-thaw cycle. Moreover, all RNA extracted from adjacent noncancerous tissues had nonqualifying RIN scores after the first freeze-thaw cycle, except for liver tissues. Microscopically, all samples displayed qualified tissue morphology regardless of freeze-thaw cycle frequency.

Conclusion: Freeze-thawing affects the RNA integrity, but not the tissue morphology of gastrointestinal cancer and paired adjacent noncancerous tissues. Furthermore, the RNA extracted from adjacent noncancerous tissues is more easily degraded than that in cancer tissues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/bio.2016.0035DOI Listing
June 2017

Long-term intravenous administration of carboxylated single-walled carbon nanotubes induces persistent accumulation in the lungs and pulmonary fibrosis via the nuclear factor-kappa B pathway.

Int J Nanomedicine 2017 30;12:263-277. Epub 2016 Dec 30.

Pharmaceutical College, Guangxi Medical University.

Numerous studies have demonstrated promising application of single-walled carbon nanotubes (SWNTs) in drug delivery, diagnosis, and targeted therapy. However, the adverse health effects resulting from intravenous injection of SWNTs are not completely understood. Studies have shown that levels of "pristine" or carboxylated carbon nanotubes are very high in mouse lungs after intravenous injection. We hypothesized that long-term and repeated intravenous administration of carboxylated SWNTs (c-SWNTs) can result in persistent accumulation and induce histopathologic changes in rat lungs. Here, c-SWNTs were administered repeatedly to rats via tail-vein injection for 90 days. Long-term intravenous injection of c-SWNTs caused sustained embolization in lung capillaries and granuloma formation. It also induced a persistent inflammatory response that was regulated by the nuclear factor-kappa B signaling pathway, and which resulted in pulmonary fibrogenesis. c-SWNTs trapped within lung capillaries traversed capillary walls and injured alveolar epithelial cells, thereby stimulating production of pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and pro-fibrotic growth factors (transforming growth factor-beta 1). Protein levels of type-I and type-III collagens, matrix metalloproteinase-2, and the tissue inhibitor of metalloproteinase-2 were upregulated after intravenous exposure to c-SWNTs as determined by immunohistochemical assays and Western blotting, which suggested collagen deposition and remodeling of the extracellular matrix. These data suggest that chronic and cumulative toxicity of nanomaterials to organs with abundant capillaries should be assessed if such nanomaterials are applied via intravenous administration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IJN.S123839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221802PMC
March 2017

The maintenance of modified electroconvulsive therapy combined with risperidone is better than risperidone alone in preventing relapse of schizophrenia and improving cognitive function.

Arq Neuropsiquiatr 2016 Oct;74(10):823-828

Shandong University, Shandong Province, China.

Objective: To evaluate the effect of maintenance modified electroconvulsive therapy (MECT) on schizophrenic patients.

Methods: From June 2012 to June 2014, 62 patients with schizophrenia, who had recovered from a successful course of acute MECT, were recruited. Thirty-one patients received maintenance MECT and risperidone, as the experimental group. Another 31 patients were enrolled in the control group, and received risperidone only. The effects on cognitive functions, clinical symptoms and relapse rate were determined.

Results: Patients in the experimental group had a lower relapse rate and longer relapse-free survival time than the controls. Relative to the baseline evaluation, patients showed statistically significant improvement in verbal memory and visual memory. At the final assessment, the scores of verbal and visual memory were remarkably lower in the experimental group than the controls but there was no significant difference in other tests.

Conclusion: Maintenance MECT plus medication is superior to medication alone in preventing relapse and improving cognitive function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/0004-282X20160130DOI Listing
October 2016