Publications by authors named "Qi Wan"

206 Publications

LINC01116 promotes tumor proliferation and neutrophil recruitment via DDX5-mediated regulation of IL-1β in glioma cell.

Cell Death Dis 2020 05 1;11(5):302. Epub 2020 May 1.

Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.

Tumor-associated neutrophils (TANs) are important inflammatory infiltrating cells in the tumor microenvironment and are closely related to the development of human tumor. However, the underlying mechanism of TANs recruiting to glioma remains unknown. Herein, we identified that LINC01116 was significantly upregulated in glioma, and positively correlated with clinical malignancy and survival prognosis. LINC01116 regulated the progression of glioma in vitro and in vivo. RNA-seq analysis demonstrated that LINC01116 knockdown affected the expression of IL-1β, which promoted glioma proliferation and neutrophil recruitment. Furthermore, the co-culture of glioma cells and neutrophils showed that the accumulation of TANs promoted tumor proliferation via producing a host of cytokines. Mechanistically, LINC01116 activated IL-1β expression by recruiting the transcriptional regulator DDX5 to the IL-1β promoter. Our findings reveal that LINC01116 can promote glioma proliferation and neutrophil recruitment by regulating IL-1β, and may be served as a novel target for glioma therapy and prognosis.
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http://dx.doi.org/10.1038/s41419-020-2506-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195423PMC
May 2020

Tocilizumab treatment in Felty's syndrome.

Rheumatol Int 2020 Jul 28;40(7):1143-1149. Epub 2020 Apr 28.

Department of Rheumatology and Immunology, Jingzhou Central Hospital, Jingzhou Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Jingzhou, 434000, China.

Felty's syndrome (FS) is a deforming disease, characterized by the triad of rheumatoid arthritis (RA), neutropenia, and splenomegaly. Currently, FS patients are treated mainly with immunosuppressants, such as methotrexate and glucocorticoids, which however are not suitable to some patients and may cause severe side effects. Here we report a clinical FS case that was treated with Tocilizumab (TCZ) successfully. The patient had symmetrical swelling and pain of multiple joints, deformity of elbow joints with obvious morning stiffness. Joint color Doppler ultrasound showed synovial hyperplasia and bone erosion of wrist and proximal interphalangeal joints and CT scan suggested splenomegaly. Further examination showed neutropenia and anemia, a high titer of anti-cyclic citrullinated peptide antibody, rheumatoid factor and anti-nuclear antibodies, positive p-ANCA, and elevated IgA and IgG. After treating with TCZ, the patient has been relieved of clinical symptoms. His spleen has recovered to normal size. The absolute neutrophil count (ANC) tended to be stable, and joint erosion did not deteriorate. We have reviewed the literatures on FS treatment with biological agents and found only a few reports using TNF-α antagonist and rituximab treating FS, but none with TCZ. So, it is the first time to report a successful FS case treated with TCZ. This case suggests that the TCZ may be a new choice for FS treatment, under the condition of closely monitoring the ANC.
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http://dx.doi.org/10.1007/s00296-020-04588-3DOI Listing
July 2020

Arginine is neuroprotective through suppressing HIF-1α/LDHA-mediated inflammatory response after cerebral ischemia/reperfusion injury.

Mol Brain 2020 04 22;13(1):63. Epub 2020 Apr 22.

Department of Neurosurgery & Pathophysiology, Institute of Neuroregeneration & Neurorehabilitation, Qingdao University, 308 Ningxia Street, Qingdao, 266071, China.

Neuroinflammation is a secondary response following ischemia stroke. Arginine is a non-essential amino acid that has been shown to inhibit acute inflammatory reaction. In this study we show that arginine treatment decreases neuronal death after rat cerebral ischemia/reperfusion (I/R) injury and improves functional recovery of stroke animals. We also show that arginine suppresses inflammatory response in the ischemic brain tissue and in the cultured microglia after OGD insult. We further provide evidence that the levels of HIF-1α and LDHA are increased after rat I/R injury and that arginine treatment prevents the elevation of HIF-1α and LDHA after I/R injury. Arginine inhibits inflammatory response through suppression of HIF-1α and LDHA in the rat ischemic brain tissue and in the cultured microglia following OGD insult, and protects against ischemic neuron death after rat I/R injury by attenuating HIF-1α/LDHA-mediated inflammatory response. Together, these results indicate a possibility that arginine-induced neuroprotective effect may be through the suppression of HIF-1α/LDHA-mediated inflammatory response in microglia after cerebral ischemia injury.
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http://dx.doi.org/10.1186/s13041-020-00601-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175589PMC
April 2020

Classification of pulmonary lesion based on multiparametric MRI: utility of radiomics and comparison of machine learning methods.

Eur Radiol 2020 Aug 28;30(8):4595-4605. Epub 2020 Mar 28.

Department of Radiology, The First Affiliated Hospital of Guangzhou Medical University, Yanjiangxilu No 151 in Yuexiu, Guangzhou, China.

Objectives: We develop and validate a radiomics model based on multiparametric magnetic resonance imaging (MRI) in the classification of the pulmonary lesion and identify optimal machine learning methods.

Materials And Methods: This retrospective analysis included 201 patients (143 malignancies, 58 benign lesions). Radiomics features were extracted from multiparametric MRI, including T2-weighted imaging (T2WI), T1-weighted imaging (TIWI), and apparent diffusion coefficient (ADC) map. Three feature selection methods, including recursive feature elimination (RFE), t test, and least absolute shrinkage and selection operator (LASSO), and three classification methods, including linear discriminate analysis (LDA), support vector machine (SVM), and random forest (RF) were used to distinguish benign and malignant pulmonary lesions. Performance was compared by AUC, sensitivity, accuracy, precision, and specificity. Analysis of performance differences in three randomly drawn cross-validation sets verified the stability of the results.

Results: For most single MR sequences or combinations of multiple MR sequences, RFE feature selection method with SVM classifier had the best performance, followed by RFE with RF. The radiomics model based on multiple sequences showed a higher diagnostic accuracy than single sequence for every machine learning method. Using RFE with SVM, the joint model of T1WI, T2WI, and ADC showed the highest performance with AUC = 0.88 ± 0.02 (sensitivity 83%; accuracy 82%; precision 91%; specificity 79%) in test set.

Conclusion: Quantitative radiomics features based on multiparametric MRI have good performance in differentiating lung malignancies and benign lesions. The machine learning method of RFE with SVM is superior to the combination of other feature selection and classifier methods.

Key Points: • Radiomics approach has the potential to distinguish between benign and malignant pulmonary lesions. • Radiomics model based on multiparametric MRI has better performance than single-sequence models. • The machine learning methods RFE with SVM perform best in the current cohort.
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http://dx.doi.org/10.1007/s00330-020-06768-yDOI Listing
August 2020

Intravoxel Incoherent Motion Diffusion-Weighted Imaging of Lung Cancer: Comparison Between Turbo Spin-Echo and Echo-Planar Imaging.

J Comput Assist Tomogr 2020 May/Jun;44(3):334-340

Department of Radiology, the First Affiliated Hospital of Guangzhou Medical University.

Objective: The aim of the study was to compare intravoxel incoherent motion diffusion-weighted imaging (DWI) for evaluating lung cancer using single-shot turbo spin-echo (TSE) and single-shot echo-planar imaging (EPI) in a 3T MR system.

Methods: Both single-shot TSE-DWI and single-shot EPI-DWI were scanned twice respectively for 15 patients with lung cancer. Distortion ratio, signal-to-noise ratio, and contrast-to-noise ratio were compared between the 2 techniques. The Bland-Altman analysis was performed to analyze reproducibility between the parameters of TSE-DWI and EPI-DWI. Short-term test-retest repeatability, as well as interobserver agreement, was evaluated using the coefficient of variation (CV) and the intraclass correlation coefficient (ICC).

Result: Turbo spin-echo DWI has lower signal-to-noise ratio and similar contrast-to-noise ratio compared with EPI-DWI. Distortion ratio of TSE-DWI was significantly smaller than that of EPI-DWI. The apparent diffusion coefficient (ADC) and true diffusivity (D) of TSE-DWI showed higher values than those of EPI-DWI. The Bland-Altman analysis showed unacceptable limits of agreement between these 2 sequences. Test-retest repeatability was good for ADC and D of EPI-DWI (CV, 14.11%-16.60% and 17.08%-19.53%) and excellent for ADC and D of TSE-DWI (CV, 4.8%-6.19% and 6.05%-8.71%), but relatively poor for perfusion fraction (f) and pseudo-diffusion coefficient (D*) (CV, 25.95%-27.70% and 56.92%-71.84% for EPI, 23.67%-28.67% and 60.85%-70.17% for TSE). For interobserver agreement, both techniques were good to excellent in ADC and D (The lower limit of 95% confidence interval for ICC was almost all greater than 0.75), whereas D* and f had higher interobserver variabilities with D* of TSE-DWI showing poorest reproducibility (ICC, -0.27 to 0.12).

Conclusions: Lung DWI or IVIM using TSE could provide distortion-free images and improve the test-retest robustness of ADC and D as compared with EPI-DWI; however, it might exert a negative effect on perfusion parameter D*.
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http://dx.doi.org/10.1097/RCT.0000000000001004DOI Listing
May 2020

Exercise ameliorates post-stroke depression by inhibiting PTEN elevation-mediated upregulation of TLR4/NF-κB/NLRP3 signaling in mice.

Brain Res 2020 06 22;1736:146777. Epub 2020 Mar 22.

Department of Rehabilitation, Affiliated Hospital of Qingdao University, Qingdao 266000, China. Electronic address:

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http://dx.doi.org/10.1016/j.brainres.2020.146777DOI Listing
June 2020

Amantadine hydrochloride monitoring by dried plasma spot technique: High-performance liquid chromatography-tandem mass spectrometry based clinical assay.

J Sep Sci 2020 Jun 8;43(12):2264-2269. Epub 2020 Apr 8.

Department of Rehabilitation Medicine, The 1st hospital of Jilin University, Changchun, P. R. China.

Amantadine plasma concentrations correlate well with desired therapeutic effects and adverse outcomes; information on amantadine exposure could be useful when multiple amantadine clearance pathways are impaired or non-compliance is suspected. Micro-sampling strategies, like dried plasma spot, would be particularly useful because ambulatory patients that do not attend a clinic can easily sample a few drops of blood by themselves at the required time of the dosing interval. We developed and validated a dried-plasma-spot-based high performance liquid chromatography-tandem mass spectrometry assay to quantify amantadine. This assay met relevant validation requirements within a hematocrit range of 20-50% and was linear from 100 to 2000 ng/mL. Amantadine was stable in dried plasma spots for up to 21 days at room temperature, regardless of whether the dried plasma spot was protected from light or not. The correlation between paired dried and wet plasma concentrations was assessed in 52 patients. Deming regression coefficients between wet plasma and simultaneously pipetted dried plasma spots were used to predict plasma concentrations. Bland-Altman plots revealed a strong agreement between dried and wet plasma concentrations, supporting the clinical usefulness of dried plasma spots for amantadine monitoring with a self-sampling strategy at a convenient time and place for the patient.
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http://dx.doi.org/10.1002/jssc.201901298DOI Listing
June 2020

Non-HIV talaromycosis: Radiological and clinical analysis.

Medicine (Baltimore) 2020 Mar;99(10):e19185

Department of Radiology, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

To investigate the characteristics of spiral computed tomography (CT), positron emission tomography-computed tomography (PET/CT) and clinical manifestations of talaromycosis to improve the diagnostic level and deepen its recognition in radiology.Radiological, clinical, and pathological manifestations of 15 patients of non-HIV talaromycosis confirmed by bronchofiberscope lung biopsy and/or abscess puncture fluid culture and/or blood culture and/or sputum culture were analyzed retrospectively. All patients underwent chest CT, among them, six had a brain MRI, and six had a PET/CT scan before treatment.On plain CT scan, there were multiple patches and massive consolidation in 6 patients, multiple patchy consolidations and patchy ground-glass opacities in 3 patients, solitary or multiple nodules and masses in 3 patients, multiple cavities and small nodules in 3 patients. Multiple lymphadenectasis appeared in bilateral hila, mediastinum, and neck in 10 patients. In contrast CT scan, the parenchyma of the lesions had a slight enhancement in 10 patients, moderate enhancement in 3 patients, obvious enhancement in 2 patients. Seven cases had bone destruction and hyperplasia, cranial involvement in 1 patient and liver involvement in 3 patients, respectively. On PET/CT, five patients showed elevated standard uptake value (SUV).The radiological manifestations of non-HIV talaromycosis show multiple consolidations, ground-glass opacities, multiple nodules or masses in bilateral lungs, deep-seated enlarged lymph nodes and bone destruction in multiple systems. The final diagnosis should be based on the culture of talaromycosis.
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http://dx.doi.org/10.1097/MD.0000000000019185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478776PMC
March 2020

Alternative Splicing Events as Indicators for the Prognosis of Uveal Melanoma.

Genes (Basel) 2020 02 21;11(2). Epub 2020 Feb 21.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510064, China.

Growing evidence has revealed that abnormal alternative splicing (AS) events are closely related to carcinogenic processes. However, the comprehensive study on the prognostic value of splicing events involved in uveal melanoma (UM) is still lacking. Therefore, splicing data of 80 UM patients were obtained from the Cancer Genome Atlas (TCGA) SpliceSeq and RNA sequence data of UM and patient clinical features were downloaded from the Cancer Genome Atlas (TCGA) database to identify survival related splicing events in UM. As a result, a total of 37996 AS events of 17911 genes in UM were detected, among which 5299 AS events of 3529 genes were significantly associated with UM patients' survival. Functional enrichment analysis revealed that this survival related splicing genes are corelated with mRNA catabolic process and ribosome pathway. Based on survival related splicing events, seven types of prognostic markers and the final overall prognostic signature could independently predict the overall survival of UM patients. Finally, an 11 spliced gene was identified in the final signature. On the basis of these 11 genes, we constructed a Support Vector Machine (SVM) classifier and evaluated it with leave-one-out cross-validation. The results showed that the 11 genes could determine short- and long-term survival with a predicted accuracy of 97.5%. Besides, the splicing factors and alternative splicing events correlation network was constructed to serve as therapeutic targets for UM treatment. Thus, our study depicts a comprehensive landscape of alternative splicing events in the prognosis of UM. The correlation network and associated pathways would provide additional potential targets for therapy and prognosis.
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http://dx.doi.org/10.3390/genes11020227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074237PMC
February 2020

Development and validation of autophagy-related-gene biomarker and nomogram for predicting the survival of cutaneous melanoma.

IUBMB Life 2020 07 21;72(7):1364-1378. Epub 2020 Feb 21.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.

Autophagy plays a critical role in cutaneous melanoma, but the prognostic research of differentially expressed autophagy-related genes (DEARGs) in melanoma is lacking. Therefore, autophagy-related gene expression data of 630 melanoma patients were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas database. The DEARGs were identified by "limma" package in R software. Best survival analysis and the least absolute shrinkage and selection operator method were performed to identify a robust 7-DEARG signature as well as construct nomogram associated with the clinical characteristics and validation in internal and external sets. This 7-DEARG signature could be regarded as an independent prognostic signature in clinical setting, and nomogram may supply a more simple and accurate prediction for the prognosis of melanoma. Moreover, 5 cancer hallmarks and 18 potential compounds are commonly enriched in high-risk expression phenotype. Thus, our finding provides new clinical evidences for the accurate diagnosis and identifies a potential prognostic autophagy-related marker for the treatment of melanoma.
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http://dx.doi.org/10.1002/iub.2258DOI Listing
July 2020

Synthesis and Antitumor Evaluation of Novel Hybrids of Phenylsulfonylfuroxan and Estradiol Derivatives.

ChemistryOpen 2020 02 11;9(2):176-182. Epub 2019 Dec 11.

Department of Medicinal Chemistry School of Pharmacy Fudan University 826, Zhangheng Road Shanghai China.

Fifteen novel furoxan-based nitric oxide (NO) releasing hybrids of estradiol derivatives were synthesized and evaluated in vitro anti-proliferative activity in MDA-MB-231, A2780, Hela and HUVEC cell lines. Most of them displayed potent anti-proliferative effects. Among the compounds, 4-bromo-3-((phenylsulfonyl)-1,2,5-oxadiazole 2-oxide)-oxy-propoxy-estradiol () exhibited the best activity with IC values of 3.58-0.0008 μM. Preliminary pharmacological studies showed that induced apoptosis and hardly affected the cell cycle of MDA-MB-231 cell line. NO-releasing capacity and inhibition of ERK/MAPK pathway signaling might explain the potent antineoplastic activity of these compounds. The preliminary structure-activity relationship (SAR) showed that steroidal scaffolds with a linker in 3-position were favorable moieties to evidently increase the bioactivities of these hybrids. Overall, these results implied that merited to be further investigated as a promising anti-cancer candidate.
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http://dx.doi.org/10.1002/open.201900228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996566PMC
February 2020

Introduction of Mercaptoethyl at Sorafenib Pyridine-2-Amide Motif as a Potentially Effective Chain to Further get Sorafenib-PEG-DGL.

Molecules 2020 Jan 28;25(3). Epub 2020 Jan 28.

Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China.

The crystal structure of the sorafenib and B-RAF complex indicates that the binding cavity occupied by the pyridine-2-carboxamide in sorafenib has a large variable space, making it a reasonable modification site. In order to identify novel compounds with anti-cancer activity, better safety and polar groups for further application, five sorafenib analogs with new pyridine-2-amide side chains were designed and synthesized. Preliminary pharmacologic studies showed that these compounds displayed much lower toxicities than that of sorafenib. Among them, compound bearing mercaptoethyl group kept relevant antiproliferation potency compared to sorafenib in Huh7 and Hela cell lines with values of IC 58.79 and 63.67 M, respectively. As a small molecule inhibitor targeting protein tyrosine kinases, thiol in compound would be an active group to react with maleimide in a mild condition for forming nanoparticles Sorafenib-PEG-DGL, which could be developed as a delivery vehicle to improve the concentration of anti-tumor therapeutic agents in the target cancer tissue and reduce side effects in the next study.
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http://dx.doi.org/10.3390/molecules25030573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037283PMC
January 2020

l-lysine confers neuroprotection by suppressing inflammatory response via microRNA-575/PTEN signaling after mouse intracerebral hemorrhage injury.

Exp Neurol 2020 05 24;327:113214. Epub 2020 Jan 24.

Department of Neurosurgery, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Rd, Wuhan 430060, China. Electronic address:

l-lysine is a basic amino acid that has been shown to exert neuroprotective effect. However, the underlying mechanism remains to be elucidated. In this study, we investigate how l-lysine exerts its neuroprotective effect in hemin-insulted mouse cortical neurons in vitro and the mouse model of intracerebral hemorrhage (ICH) in vivo. We demonstrate that l-lysine treatment promotes M2 microglial polarization and reduces inflammatory response both in vitro and in vivo, suggesting that l-lysine may play a neuroprotective role in ICH injury. Indeed, we show that l-lysine treatment reduces cortical neuronal death after hemin insult in vitro and decrease the number of degenerating neurons after ICH in vivo. l-lysine also improves the functional recovery of ICH animals in neurobehavioral tests. Consistent with the role of PTEN in regulating inflammatory response, we find that PTEN inhibition promotes M2 microglial polarization and suppresses pro-inflammatory response in mouse ICH injury, which contribute to the neuroprotective effect of l-lysine. Moreover, our results reveal that microRNA-575 directly suppressed PTEN to promote M2 microglial polarization and mediate the neuroprotective effect of l-lysine in ICH injury. Together, our results suggest that l-lysine confers neuroprotection after ICH injury through enhancing M2 microglial polarization and reducing inflammatory response, which is mediated by microRNA-575 upregulation and subsequent PTEN downregulation.
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http://dx.doi.org/10.1016/j.expneurol.2020.113214DOI Listing
May 2020

A novel squaramide compound alleviates cognitive deficits through activation of Akt and Erk1/2 in a rat model of vascular dementia.

J Integr Neurosci 2019 Dec;18(4):401-408

Department of Physiology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, 442000, P. R. China.

Vascular dementia is the second most common type of dementia, yet no effective treatment for it exists. Akt and Erk1/2 signaling pathways are involved in neuronal survival. It has been reported that bisperoxovanadium (pyridin-2-squaramide), a novel squaramide compound, protects against cerebral ischemia injury via activation of Akt and Erk1/2. Here, the potential neuroprotective effect of bisperoxovanadium is shown for the first time in a model of vascular dementia induced in 6-month-old male Sprague-Dawley rats by two-vessel occlusion injury applied to 6-month-old. Following this lesion, bisperoxovanadium (pyridin-2-squaramide) (1 mg/kg/day) was intragastrically administered for four successive weeks. The Morris water maze test estimated cognitive function. The morphological examination was performed by hematoxylin-eosin staining. Akt and Erk1/2 protein abundance were assessed by Western blot. Results showed that bisperoxovanadium (pyridin-2-squaramide) attenuated not only cognitive dysfunction but also alleviated histopathological changes in rats with vascular dementia. Moreover, bisperoxovanadium (pyridin-2-squaramide) ultimately reduced neuronal apoptosis represented by the Bax/Bcl-2 ratio in the CA1 (cornu ammonis 1) region of the hippocampus. Importantly, the levels of p-Akt(ser473) and p-Erk1/2(Thr202/Tyr204>) were increased after treatment with bisperoxovanadium (pyridin-2-squaramide). It is concluded that the novel squaramide compound bisperoxovanadium (pyridin-2-squaramide) might be effective in the treatment of vascular dementia by activation of Akt and Erk1/2.
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http://dx.doi.org/10.31083/j.jin.2019.04.1204DOI Listing
December 2019

Six-gene-based prognostic model predicts overall survival in patients with uveal melanoma.

Cancer Biomark 2020 ;27(3):343-356

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, Guangdong, China.

Background: Uveal melanoma (UM) is the most common primary intraocular tumor in adults, which has a high mortality rate and worse prognosis. Therefore, early potential molecular detection and prognostic evaluation seem more important for early diagnosis and treatment.

Methods: Gene expression data were obtained from The Cancer Genome Atlas-Uveal melanomas database. Survival genes were identified by univariate analysis and were regarded to be associated with the overall survival of UM patients. Then, pathway enrichment analysis of these survival genes was performed. Robust likelihood-based survival model and multivariate survival analysis were conducted to identify more reliable genes and the prognostic signature for UM survival prediction. Two internal datasets and another two UM datasets from Gene Expression Omnibus (GEO) were used for the validation of prognostic signature.

Results: Firstly, 2,010 survival genes were screened by univariate survival analysis. GO and KEGG analysis revealed that these genes were mainly involved in pathways such as mRNA processing, RNA splicing, spliceosome and ubiquitin mediated proteolysis. Secondly, a six-gene signature was identified by Robust likelihood-based survival model approach. The gene expression of the six genes can successfully divide UM samples into high- and low-risk groups and have strong survival prediction ability. What's more, the expression of six genes was compared in 80 healthy adipose tissue samples obtained from GTEx (Genotype-Tissue Expression) database and further validated in internal datasets and GEO datasets, which also can predict UM patient survival.

Conclusions: The six genes (SH2D3A, TMEM201, LZTS1, CREG1, NIPA1 and HIST1H4E) model might play a vital role in prognosis of UM, which should be helpful for further insight into the treatment of uveal melanoma.
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http://dx.doi.org/10.3233/CBM-190825DOI Listing
November 2020

Collaborative Design of Hollow Nanocubes, In Situ Cross-Linked Binder, and Amorphous [email protected] @C as a Three-Pronged Strategy for Ultrastable Lithium Storage.

Small 2020 Feb 23;16(5):e1905736. Epub 2019 Dec 23.

Institute for Advanced Materials and Technology, University of Science and Technology Beijing, Beijing, 100083, China.

Although silicon-based materials are ideal candidate anodes for high energy density lithium-ion batteries, the large volumetric expansion seriously damages the integrity of the electrodes and impedes commercial processes. Reasonable electrode design based on adjustable structures of silicon and strong binders prepared by a facile method is still a great challenge. Herein, a three-pronged collaborative strategy via hollow nanocubes, amorphous [email protected] @C, and in situ cross-linked polyacrylic acid and d-sorbitol 3D network binder (c-PAA-DS) is adopted to maintain structural/electrode integrality and stability. The all-integrated c-PAA-DS/[email protected] @C electrode delivers excellent mechanical property, which is attributed to ductility of the c-PAA-DS binder and high adhesion energy between [email protected] @C and c-PAA-DS calculated by density functional theory. Benefiting from the synergistic effect of accommodation of the hollow structure, protection of outer carbon shell, amorphous [email protected] @C, and strong adhesive c-PAA-DS binder, c-PAA-DS/[email protected] @C shows excellent electrochemical performance. Long cycling stability with a reversible capacity of 696 mAh g is obtained, as well as tiny capacity decay after 500 cycles at 0.5 A g and high-rate performance. The prelithiated [email protected] @C||LiNi Co Mn O (NCM523) full cell is also assembled and shows a reversible capacity of 157 mAh g at 0.5 C, delivering an excellent capacity retention of 94% after 160 cycles.
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http://dx.doi.org/10.1002/smll.201905736DOI Listing
February 2020

PTEN Inhibition Protects Against Experimental Intracerebral Hemorrhage-Induced Brain Injury Through PTEN/E2F1/β-Catenin Pathway.

Front Mol Neurosci 2019 5;12:281. Epub 2019 Dec 5.

Institute of Neuroregeneration and Neurorehabilitation, Department of Neurosurgery of the Affiliated Hospital, Qingdao University, Qingdao, China.

Intracerebral hemorrhage (ICH) is a subtype of stroke with highest mortality and morbidity. We have previously demonstrated that dipotassium bisperoxo (picolinato) oxovanadate (V), (bpV[pic]) inhibits phosphatase and tensin homolog (PTEN) and activates extracellular signal-regulated kinase (ERK)1/2. In this study, we examined the effect of bpV[pic] in the rat ICH model and the hemin-induced injury model in rat cortical cultures. The rat model of ICH was created by injecting autologous blood into the striatum, and bpV[pic] was intraperitoneally injected. The effects of bpV[pic] were evaluated by neurological tests, Fluoro-Jade C (FJC) staining, and Nissl staining. We demonstrate that bpV[pic] attenuates ICH-induced brain injury and hemin-induced neuron injury . The expression of E2F1 was increased, but β-catenin expression was decreased after ICH, and the altered expressions of E2F1 and β-catenin after ICH were blocked by bpV[pic] treatment. Our results further show that bpV[pic] increases β-catenin expression through downregulating E2F1 in cortical neurons and prevents hemin-induced neuronal damage through E2F1 downregulation and subsequent upregulation of β-catenin. By testing the effect of PTEN-siRNA, PTEN cDNA, or combined use of ERK1/2 inhibitor and bpV[pic] in cultured cortical neurons after hemin-induced injury, we provide evidence suggesting that PTEN inhibition by bpV[pic] confers neuroprotection through E2F1 and β-catenin pathway, but the neuroprotective role of ERK1/2 activation by bpV[pic] cannot be excluded.
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http://dx.doi.org/10.3389/fnmol.2019.00281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906195PMC
December 2019

Gastrodin Ameliorates Motor Learning Deficits Through Preserving Cerebellar Long-Term Depression Pathways in Diabetic Rats.

Front Neurosci 2019 22;13:1239. Epub 2019 Nov 22.

Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, China.

Cognitive dysfunction is a very severe consequence of diabetes, but the underlying causes are still unclear. Recently, the cerebellum was reported to play an important role in learning and memory. Since long-term depression (LTD) is a primary cellular mechanism for cerebellar motor learning, we aimed to explore the role of cerebellar LTD pathways in diabetic rats and the therapeutic effect of gastrodin. Diabetes was induced by a single injection of streptozotocin into adult Sprague-Dawley rats. Motor learning ability was assessed by a beam walk test. Pathological changes of the cerebellum were assessed by Hematoxylin-Eosin (HE) and Nissl staining. Cellular apoptosis was assessed by anti-caspase-3 immunostaining. Protein expression levels of LTD pathway-related factors, including GluR2, protein kinase C (PKC), NR2A, and nNOS, in the cerebellar cortex were evaluated by western blotting and double immunofluorescence. The NO concentration was measured. The cellular degeneration and the apoptosis of Purkinje cells were evident in the cerebellum of diabetic rats. Protein expression levels of GluR2 (NC9W: 1.26 ± 0.12; DM9W + S: 0.81 ± 0.07), PKC (NC9W: 1.66 ± 0.10; DM9W + S: 0.58 ± 0.19), NR2A (NC9W: 1.40 ± 0.05; DM9W + S: 0.63 ± 0.06), nNOS (NC9W: 1.26 ± 0.12; DM9W + S: 0.68 ± 0.04), and NO (NC9W: 135.61 ± 31.91; DM9W + S: 64.06 ± 24.01) in the cerebellum were significantly decreased in diabetic rats. Following gastrodin intervention, the outcome of motor learning ability was significantly improved (NC9W: 6.70 ± 3.31; DM9W + S: 20.47 ± 9.43; DM9W + G: 16.04 ± 7.10). In addition, degeneration and apoptosis were ameliorated, and this was coupled with the elevation of the protein expression of the abovementioned biomarkers. Arising from the above, we concluded that gastrodin may contribute to the improvement of motor learning by protecting the LTD pathways in Purkinje cells.
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http://dx.doi.org/10.3389/fnins.2019.01239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883220PMC
November 2019

Prevalence, burden, and clinical management of migraine in China, Japan, and South Korea: a comprehensive review of the literature.

J Headache Pain 2019 Dec 5;20(1):111. Epub 2019 Dec 5.

Medicine Development Unit-Japan, Eli Lilly Japan K.K., 5-1-28, Isogamidori, chuo-ku, Kobe, 651-0086, Japan.

Background: The objective of this review was to determine the unmet needs for migraine in East Asian adults and children.

Methods: We searched MEDLINE and EMBASE (January 1, 1988 to January 14, 2019). Studies reporting the prevalence, humanistic and economic burden, and clinical management of migraine in China (including Hong Kong and Taiwan), Japan, and South Korea were included. Studies conducted before 1988 (before the International Headache Society [IHS] first edition of the International Classification of Headache Disorders) were not included.

Results: We retrieved 1337 publications and 41 met the inclusion criteria (28 from China, 7 from Japan, and 6 from South Korea). The 1-year prevalence of migraine (IHS criteria) among adults ranged from 6.0% to 14.3%. Peak prevalence ranged from 11% to 20% for women and 3% to 8% for men (30- to 49-year-olds). For children, prevalence of migraine increased with age. Information on the economic burden and clinical management of migraine was limited, particularly for children. When reported, migraine was significantly associated with high levels of disability and negative effects on quality of life. Studies suggested low levels of disease awareness/diagnosis within each country. Of individuals with migraine from China, 52.9% to 68.6% had consulted a physician previously, 37.2% to 52.7% diagnosed with headache had not been diagnosed with migraine previously, and 13.5% to 18% had been diagnosed with migraine previously. Of individuals with migraine from Japan, 59.4% to 71.8% had never consulted a physician previously, 1.3% to 7.3% regularly consulted physicians for their headache, and only 11.6% of individuals with migraine were aware that they had migraine. In addition, studies suggested that over-the-counter medication use was high and prescription medication use was low in each country.

Conclusions: This review suggests that there are unmet needs for migraine in terms of sufficient and appropriate diagnosis, and better management and therapies for treatment of migraine in East Asia. The findings are limited by a lack of recent information and significant gaps in the literature. More recent, population-based studies assessing disease burden and clinical management of migraine are needed to confirm unmet needs for migraine across East Asia.
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http://dx.doi.org/10.1186/s10194-019-1062-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896325PMC
December 2019

Surgical treatment of corneal dermoid by using intrastromal lenticule obtained from small-incision lenticule extraction.

Int Ophthalmol 2020 Jan 17;40(1):43-49. Epub 2019 Nov 17.

Department of Ophthalmology, The People's Hospital of Leshan, Leshan City, 614000, People's Republic of China.

Purpose: To report a novel technique to treat superficial limbal dermoid by using the corneal intrastromal lenticules obtained from SMILE and to evaluate the initial clinical outcomes of lenticule patch graft for treatment of limbal dermoid.

Methods: In this single-center case series, lenticules were obtained from patients undergoing SMILE for the correction of myopia and the lenticule patch graft was performed in three patients with limbal dermoid. Patients were postoperatively followed at first, second weeks and first, third months after surgery. The main measured outcome parameters were included the best-corrected visual acuity, transparency of graft, tectonic integrity and restoration of optical transparency.

Results: All surgeries were successful, and all patients recovered well. Obviously, improving tendency in visual acuity and astigmatism was seen at the final follow-up in all eyes. No statistically significant difference has found in the thickness of the cornea between the surgical field and the corresponding normal field. Globe integrity was achieved in all cases, and no immune rejection or perforation was detected until the last follow-up visit in all eyes treated.

Conclusions: Lenticule keratoplasty may be a safe, feasible and inexpensive surgical option for the treatment of corneal dermoid. It retains globe integrity and decreases the risk of complications such as postoperative limbal ectasia and visible corneal scarring and should be widely promoted in the areas with shortage of donor corneas.
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http://dx.doi.org/10.1007/s10792-019-01201-wDOI Listing
January 2020

MicroRNA-26b/PTEN Signaling Pathway Mediates Glycine-Induced Neuroprotection in SAH Injury.

Neurochem Res 2019 Nov 14;44(11):2658-2669. Epub 2019 Oct 14.

Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, 430060, China.

Subarachnoid hemorrhage (SAH) is a form of stroke associated with high mortality and morbidity. Despite advances in treatment for SAH, the prognosis remains poor. We have previously demonstrated that glycine, a non-essential amino acid is involved in neuroprotection following intracerebral hemorrhage via the Phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) signaling pathway. However, whether it has a role in inducing neuroprotection in SAH is not known. The present study was designed to investigate the role of glycine in SAH. In this study, we show that glycine can reduce brain edema and protect neurons in SAH via a novel pathway. Following a hemorrhagic episode, there is evidence of downregulation of S473 phosphorylation of AKT (p-AKT), and this can be reversed with glycine treatment. We also found that administration of glycine can reduce neuronal cell death in SAH by activating the AKT pathway. Glycine was shown to upregulate miRNA-26b, which led to PTEN downregulation followed by AKT activation, resulting in inhibition of neuronal death. Inhibition of miRNA-26b, PTEN or AKT activation suppressed the neuroprotective effects of glycine. Glycine treatment also suppressed SAH-induced M1 microglial polarization and thereby inflammation. Taken together, we conclude that glycine has neuroprotective effects in SAH and is mediated by the miRNA-26b/PTEN/AKT signaling pathway, which may be a therapeutic target for treatment of SAH injury.
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http://dx.doi.org/10.1007/s11064-019-02886-2DOI Listing
November 2019

Emodin promotes fibroblast apoptosis and prevents epidural fibrosis through PERK pathway in rats.

J Orthop Surg Res 2019 Oct 10;14(1):319. Epub 2019 Oct 10.

Department of Orthopedics, Clinical Medical College of Yangzhou University, Orthopaedic Institute, Northern Jiangsu People's Hospital, Yangzhou, 225001, China.

Background: Laminectomy is usually classed as a common orthopedic surgery, but postoperative epidural fibrosis often leads to less-than-desirable clinical outcomes. As demonstrated by prior studies, emodin (EMO) exerts an anti-fibrotic effect. Here, we carried out investigation into the inhibitory effect created by EMO application on epidural fibrosis after laminectomy in rats.

Methods: The paper conducts a series of experiment. In vitro, we observed the effect of EMO on fibroblasts by Cell Counting Kit-8 (CCK-8) assay. Apoptosis of fibroblasts induced by EMO was detected by western blot, TUNEL assay, and flow cytometry. The results revealed that EMO was capable of inducing fibroblast apoptosis, and the proteins of PERK pathway also changed accordingly. In vivo, the effect of EMO on epidural fibrosis in 12 male Sprague-Dawley rats was observed by histological staining.

Results: CCK-8 assay indicated that EMO was effective in reducing fibroblast viability in a time- and a dose-dependent manner. TUNEL assay and flow cytometry analysis have demonstrated that the apoptotic rate of fibroblasts increased as the EMO concentration rose. Western blot analysis proved that EMO promoted the relative expression of p-perk and p-eIF2α and that the expression of its downstream proteins CHOP and GRP78 was also enhanced. The expression of apoptotic protein Bax and cleaved PARP was upregulated, whereas the expression of anti-apoptotic protein Bcl-2 was downregulated. In addition, histological and immunohistochemical analysis demonstrated that EMO functioned to inhibit epidural fibrosis and increase GRP78 expression in fibrous tissue by promoting apoptosis of fibroblasts.

Conclusions: EMO could have inhibitory effect on epidural fibrosis in a concentration-dependent manner. The potential mechanism might be through PERK signaling pathway to promote fibroblast apoptosis. It has a possibility to be taken as a novel method for the treatment of epidural fibrosis.
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http://dx.doi.org/10.1186/s13018-019-1357-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785852PMC
October 2019

Efficacy and Safety of Toutongning Capsule in Patients with Migraine: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

J Altern Complement Med 2019 Dec 25;25(12):1215-1224. Epub 2019 Sep 25.

Department of Neurology, Fuling Center Hospital of Chongqing City, Chongqing, P.R. China.

Toutongning (TTN) capsule, a Chinese patent medicine, is used as a prophylactic treatment for migraine. The present study was conducted as a postmarketing evaluation of the efficacy and safety of TTN capsule. A randomized, double-blind, placebo-controlled trial. Patients recruited from 14 medical centers in China from May 2014 to August 2015. Patients between 18 and 65 years of age with a diagnosis of migraine. The patients were randomly assigned to receive either TTN (1200 mg, three times daily) or a matched placebo (1:1) for 4 weeks. The primary outcome measured was a minimum 50% reduction in the frequency of headaches from the 4-week baseline period to the last 4 weeks of the 12-week trial. Secondary outcomes included duration, days, and visual analog score of headache attack, interval between headache attacks, usage of acute analgesics, and score on the Headache Impact Test-6. In addition, all patients were evaluated for adverse events (AEs). This study initially enrolled 400 patients; a total of 378 participants completed the experiment while fulfilling all study requirements. TTN had a superior effect compared with the placebo on both the primary and secondary outcome measures without any serious AEs or unexpected side effects. TTN can effectively prevent the occurrence of migraine headaches and is well-tolerated and safe. TTN may exhibit a persistent therapeutic effect even after cessation of use. Trial Registration number: ChiCTR-IPR-15007058.
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http://dx.doi.org/10.1089/acm.2018.0500DOI Listing
December 2019

Nitric oxide and hydrogen peroxide increase glucose-6-phosphate dehydrogenase activities and expression upon drought stress in soybean roots.

Plant Cell Rep 2020 Jan 18;39(1):63-73. Epub 2019 Sep 18.

Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, School of Life Sciences, Lanzhou University, Lanzhou, 730000, Gansu, China.

Key Message: Changes in glucose-6-phosphate dehydrogenase (G6PD) isoforms activities and expression were investigated in soybean roots under drought, suggesting that cytosolic G6PD plays a main role by regulating HO signal and redox homeostasis. G6PD acts a vital role in plant growth, development and stress adaptation. Drought (PEG6000 treatment) could markedly increase the enzymatic activities of cytosolic G6PD (Cyt-G6PD) and compartmented G6PD (mainly plastidic P2-G6PD) in soybean roots. Application of G6PD inhibitor upon drought condition dramatically decreased the intracellular NADPH and reduced glutathione levels in soybean roots. Nitric oxide (NO) and hydrogen peroxide (HO) participated in the regulation of Cyt-G6PD and P2-G6PD enzymatic activities under drought stress. Diphenylene iodonium (DPI), an inhibitor of NADPH oxidase, abolished the drought-induced accumulation of HO. The exogenous application of HO and its production inhibitor (DPI) could stimulate and inhibit the NO accumulation, respectively, but not vice versa. qRT-PCR analysis confirmed that NO, as the downstream signal of HO, positively regulated the transcription of genes encoding Cyt-G6PD (GPD5, G6PD6, G6PD7) under drought stress in soybean roots. Comparatively, NO and HO signals negatively regulated the gene expression of compartmented G6PD (GPD1, G6PD2, G6PD4), indicating that a post-transcriptional mechanism was involved in compartmented G6PD regulation. Taken together, the high Cyt-G6PD activity is essential for maintaining redox homeostasis upon drought condition in soybean roots, and the HO-dependent NO cascade signal is differently involved in Cyt-G6PD and compartmented G6PD regulation.
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http://dx.doi.org/10.1007/s00299-019-02473-3DOI Listing
January 2020

Apigenin inhibits fibroblast proliferation and reduces epidural fibrosis by regulating Wnt3a/β-catenin signaling pathway.

J Orthop Surg Res 2019 Aug 14;14(1):258. Epub 2019 Aug 14.

Department of Orthopedics, Clinical Medical College of Yangzhou University, Orthopaedic Institute, Northern Jiangsu People's Hospital, Yangzhou, 225001, China.

Background: Failed back surgery syndrome (FBSS) is a common complication after the laminectomy. Epidural fibrosis is the major cause of lower back pain and other complications. Numerous studies have shown that apigenin (API) could treat various fibrotic diseases by regulating various signaling pathways, whereas no study has discussed whether API can inhibit fibroblast proliferation and reduce epidural fibrosis after the laminectomy by regulating Wnt3a/β-catenin signaling pathway.

Methods: Human fibroblasts were cultured and treated with API in different concentrations for 24 h. CCK-8 detection and EdU incorporation assay were performed to detect cell viability and cell proliferation. Western blotting analysis was applied to detect expressions of proliferative proteins, Wnt3a, and its downstream proteins. Moreover, the Wnt3a gene was overexpressed in fibroblasts to define the relationship between Wnt3a/β-catenin signaling pathway and fibroblast proliferation. Wnt3a overexpressed fibroblasts were treated with API to verify if it could reverse the effects of API treatment. Twenty-four Sprague-Dawley rats were randomly divided into four groups. Laminectomy was performed and the rats were gavaged with different doses of API or 5% sodium carboxyl methyl cellulose (CMC-Na) solution for 1 month. The abilities of API to inhibit fibroblast proliferation and to reduce epidural fibrosis were evaluated using histological and immunohistochemical analysis.

Results: CCK-8 detection and EdU incorporation assay demonstrated that API could inhibit the viability and proliferation rate of fibroblasts in a concentration-dependent manner. The Western blotting analysis revealed that API could inhibit the expressions of PCNA, cyclinD1, Wnt3a, and its downstream proteins. The overexpression of Wnt3a in fibroblasts could upregulate the expressions of proliferative proteins such as PCNA and cyclinD1. The inhibitory effect of API on PCNA, Wnt3a, and its downstream proteins was partially reversed by overexpression of Wnt3a. Moreover, the results of the histological and immunohistochemical analysis revealed that API could reduce the epidural fibrosis in rats by inhibiting fibroblast proliferation in a dose-dependent manner.

Conclusions: API can inhibit fibroblast proliferation and reduce epidural fibrosis by suppressing Wnt3a/β-catenin signaling pathway, which can be adopted as a new option to prevent epidural fibrosis after the laminectomy.
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http://dx.doi.org/10.1186/s13018-019-1305-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694561PMC
August 2019

The neuroprotective effect of bisperoxovandium (pyridin-2-squaramide) in intracerebral hemorrhage.

Drug Des Devel Ther 2019 13;13:1957-1967. Epub 2019 Jun 13.

Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming 650500, People's Republic of China.

The authors have recently designed a new compound bisperoxovandium (pyridin-2-squaramide) [bpV(pis)] and verified that bpV(pis) confers neuroprotection through suppressing PTEN and activating ERK1/2, respectively. Intracerebral hemorrhage (ICH) is the second most common cause of stroke and has severe clinical outcome. In this study, we investigate the effect of bpV(pis) in ICH model both in vivo and in vitro. The novel drug bpV(pis) was synthesized in the Faculty of Pharmacy, Wuhan University School of Medicine. An ICH model was generated on both SD rats and cells. bpV(pis) was injected into intracerebroventricular or culture media. Western blotting was applied to test the signal pathway. To determine the effect of bpV(pis) on PTEN inhibition and ERK1/2 activation, we measured the phosphorylation level of AKT (a direct downstream target of PTEN that negatively regulates AKT) and ERK1/2. FJC, MTT, and LDH were applied to measure the cell viability. Neurobehavioral tests were performed to measure the effect of bpV(pis). The in vivo results showed that intracerebroventricular administration of bpV(pis) significantly alleviates hematoma, the damage of brain-blood barrier and brain edema. The in vitro results demonstrated that bpV(pis) treatment reduces ICH-induced neuronal injury. Western blotting results identified that bpV(pis) exerts a neuroprotective effect by significantly increasing the phosphorylation level of AKT and ERK1/2 after experimental ICH. Neurobehavioral tests indicate that bpV(pis) promotes functional recovery in ICH animals. This study provides first and direct evidence for a potential role of bpV(pis) in ICH therapy.
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http://dx.doi.org/10.2147/DDDT.S204956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585412PMC
February 2020

Exploration of potential key pathways and genes in multiple ocular cancers through bioinformatics analysis.

Authors:
Qi Wan Jing Tang

Graefes Arch Clin Exp Ophthalmol 2019 Oct 15;257(10):2329-2341. Epub 2019 Jul 15.

Department of Ophthalmology, The People's Hospital of Leshan, Leshan, 614000, China.

Purpose: Primary cancers of the eye are common in ocular diseases. The objective of this study was to explore the underlying mechanisms and the potential target genes in multiple ocular cancers by bioinformatics approach.

Method: These gene expression profiles of GSE24673 (Retinoblastoma), GSE44295 (Uveal melanoma), and GSE103439 (Basal cell carcinoma of the eyelid) were downloaded from Gene Expression Omniniub (GEO) database. The differentially expressed genes (DEGs) in the three gene chips were identified by limma package in R software and gene integration was performed by using "RobustRankAggreg" package. Gene set enrichment analysis (GSEA) and the Gene Ontology (GO) were performed to the selected genes. Moreover, survival analysis was used to estimate uveal melanoma dataset.

Results: In total, 509 DEGs were identified in GSE24673 (retinoblastoma), 305 DEGs were identified in GSE44295 (uveal melanoma), and 753 DEGs were identified in GSE103439 (basal cell carcinoma of the eyelid). Among those genes, only IGF2BP3 was shared for the three cancer types. A total of 20 DEGs were identified through gene integration (score < 0.05) and IGF2BP3 was ranked the top. Moreover, GO analysis results showed that the 20 DEGs were significantly enriched in WNT signaling pathway, DNA damage, and apoptotic process. GSEA showed that pathways related with cellular respiratory chain are differentially enriched in IGF2BP3 low expression phenotype. Finally, two genes (ID3 and SLC6A15) can predict the overall survival in uveal melanoma patients.

Conclusions: This findings and results of study showed that the identification of DEGs and key pathways gives a promotion to understand the molecular mechanisms underlying the development of ocular cancers, which contribute to a more comprehensive understanding of cancers of the eye and provide new insights for these studies at gene level.
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http://dx.doi.org/10.1007/s00417-019-04410-2DOI Listing
October 2019

NKT Cells in Neurological Diseases.

Authors:
Yu Cui Qi Wan

Front Cell Neurosci 2019 29;13:245. Epub 2019 May 29.

Institute of Neuroregeneration and Neurorehabilitation, Qingdao University, Qingdao, China.

Natural killer T (NKT) cells are a unique subset of T lymphocytes with the expression of T cell receptor (TCR) and NK cell lineage receptors. These cells can rapidly release large quantities of cytokines and function as a bridge between innate and adaptive immunity. To date, multiple reports have investigated the role of NKT cells under various pathological conditions, such as cancer, autoimmune disease, and infection. Knowledge about NKT cells in neurological diseases is increasing, albeit limited. Here, we review evidence for the involvement of NKT cells in neurological diseases, and discuss immunotherapeutic potential and future study goals. As the development and function of NKT cells become increasingly well understood, the next few years should yield many new insights into NKT cell function, and mechanistic regulation in neurological disorders.
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http://dx.doi.org/10.3389/fncel.2019.00245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558384PMC
May 2019

Analysis of microbiota in elderly patients with Acute Cerebral Infarction.

PeerJ 2019 12;7:e6928. Epub 2019 Jun 12.

Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.

Background And Aims: Recent evidence suggest that microbiota is associated with almost all major types of diseases, including cardiovascular diseases. However, its role in Acute Cerebral Infarction remains unexplored. It is important to understand the diversity and distribution of gut microbiota (GM) in patients with Acute Cerebral Infarction and the role that GM plays in this type of disease.

Methods: We performed pyrosequencing on the gut microbiota of 40 individuals in order to elucidate whether the composition of the microbiota differs between patients with Acute Cerebral Infarction and healthy controls: Of these individuals, there were 31 with Acute Cerebral Infarction and nine controls. We applied linear regression to calculate the correlation between the gut flora and disease risk factors. Finally, KEGG functional enrichment analysis was conducted to examine the correlation between the gut flora and Acute Cerebral Infarction.

Results: The overall microbial structure was similar in both the controls and the patients, but the control group had higher relative presence of while the presence of and were relatively higher in the patient group. Using linear regression, we found that was negatively associated with white blood cell count and was positively correlated with creatinine and lipoprotein. The KEGG pathway analysis indicated that the bio-pathways including methane metabolism, lipopolysaccharide synthesis, bacterial secretion, and flagellar assembly of the gut microbiota in the patient group was expressed differently than that of the controls. We identified three differentially expressed gut microbial functions in Acute Cerebral Infarction and found four bacterial pathways that might be related to the development of this disease.

Conclusions: Our study identified three abnormally-expressed bacteria-, and -in patients with Acute Cerebral Infarction compared with healthy controls. It reveals a correlation of these bacterial species with Acute Cerebral Infarction as they relate to disease factors and functional pathways. These findings may shed light on the treatment of cerebral infarction because gut microbiota could serve as a potential therapeutic approach for the treatment of cardiovascular and metabolic diseases.
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http://dx.doi.org/10.7717/peerj.6928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571007PMC
June 2019

Corneal subbasal nerve plexus changes in patients with episodic migraine: an in vivo confocal microscopy study.

J Pain Res 2019 13;12:1489-1495. Epub 2019 May 13.

Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People's Republic of China.

It has been generally thought that activation and sensitization of the trigeminovascular system may contribute to the pathogenesis of migraine. Nevertheless, there is little evidence on abnormalities in peripheral trigeminal afferent nerves from humans in vivo. Alterations of corneal nerves from the ophthalmic branch of the trigeminal nerve may support the notion that trigeminal afferent nerves are involved in migraine pathophysiology. The aim of the present study was to investigate the structural changes in corneal subbasal nerve plexus in patients with episodic migraine (EM) with in vivo confocal microscope (IVCM). In this cross-sectional observational study, 10 EM patients and 10 age- and sex-matched healthy controls were included. Analysis of IVCM images with Image J software was performed to quantify the changes in the corneal subbasal nerve plexus. EM patients showed an increase in nerve fiber length (25.0±2.65 vs 22.3±2.41 mm/mm, =0.047) and nerve fiber density (36.3±7.29 vs 30.5±6.19 fibers/mm, =0.104) as compared with normal controls, but this difference was not statistically significant. Nerve branching and tortuosity were significantly increased in the EM subjects compared to the normal subjects (91.3±13.8 vs 75.0±14.2 branches/mm, =0.030 and 2.30±0.46 versus 1.63±0.52, =0.011, respectively). In addition, nerve sprouts and increased number of Langerhans cells were observed in the EM patients. The morphologic changes of corneal subbasal nerve plexus and Langerhans cell aggregation suggest the presence of nerve regeneration and inflammation in EM. Furthermore, the alterations of corneal nerves from the ophthalmic branch of the trigeminal nerve offer support for the hypothesis that the peripheral trigeminal system may be involved in the pathogenesis of migraine.
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http://dx.doi.org/10.2147/JPR.S196705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526177PMC
May 2019
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