Publications by authors named "Shanshan Qin"

86 Publications

Up-regulation of the long non-coding RNA Xist and the imbalance sex/ratio of pulmonary arterial hypertension.

Am J Pathol 2021 Apr 6. Epub 2021 Apr 6.

Pulmonary arterial hypertension (PAH) is a sex-biased disease. Recent studies demonstrated that the increased expression and activity of the long-noncoding (lnc)RNA-Xist, essential for X-chromosome (X-Chr) inactivation and dosage compensation of X-linked genes, may explain the imbalance sex/ratio of PAH. The present studies, using a murine model of plexiform PAH, the intersectin-1s (ITSN) heterozygous (KO) mouse transduced with an ITSN fragment (EH) possessing endothelial cell proliferative activity, in conjunction with molecular, cell biology, biochemical, morphological and functional approaches, demonstrate significant sex-centered differences with regard to EH-induced alterations in pulmonary artery remodeling, lung hemodynamics and p38/Elk1/c-Fos signaling, altogether leading to a more severe female lung PAH phenotype. Moreover, the lncRNA-Xist is upregulated in the lungs of female EH-KO mice compared to female wt-mice, leading to sex-specific modulation of the X-linked gene Elk1 and its target, two molecular events also characteristic to female human PAH lung. Importantly, cyclin A1 expression in the S- and G2/M-phases of the cell cycle of syncronized pulmonary artery endothelial cells (PAECs) of female PAH patients is greater vs. controls, suggesting functional hyper-proliferation. Thus, Xist upregulation leading to females' PAECs sexual dimorphic behavior may provide a better understanding of the origin of sex bias in PAH. Notably, the EH-KO mouse is a unique experimental animal model of PAH that recapitulates most of the sexually dimorphic characteristics of human disease.
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http://dx.doi.org/10.1016/j.ajpath.2021.03.009DOI Listing
April 2021

Contrastive Similarity Matching for Supervised Learning.

Neural Comput 2021 Feb 22:1-29. Epub 2021 Feb 22.

John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, U.S.A.

We propose a novel biologically plausible solution to the credit assignment problem motivated by observations in the ventral visual pathway and trained deep neural networks. In both, representations of objects in the same category become progressively more similar, while objects belonging to different categories become less similar. We use this observation to motivate a layer-specific learning goal in a deep network: each layer aims to learn a representational similarity matrix that interpolates between previous and later layers. We formulate this idea using a contrastive similarity matching objective function and derive from it deep neural networks with feedforward, lateral, and feedback connections and neurons that exhibit biologically plausible Hebbian and anti-Hebbian plasticity. Contrastive similarity matching can be interpreted as an energy-based learning algorithm, but with significant differences from others in how a contrastive function is constructed.
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http://dx.doi.org/10.1162/neco_a_01374DOI Listing
February 2021

miRNA-194 predicts favorable prognosis in gastric cancer and inhibits gastric cancer cell growth by targeting CCND1.

FEBS Open Bio 2021 Feb 19. Epub 2021 Feb 19.

Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.

MicroRNAs (MiRNAs) play critical roles in regulating target gene expression and multiple cellular processes in human cancer malignant progression. However, the function of miR-194 in gastric cancer (GC) remains unclear and controversial. In this study, we identified a series of miRNAs that can serve as prognostic biomarkers for GC by analysis of miRNA expression using The Cancer Genome Atlas data. Among them, miR-100, miR-125b, miR-199a, and miR-194 were the four most promising prognostic biomarkers in GC due to their significant associations with various clinical characteristics of patients. miR-100, miR-125b, and miR-199a predicted poor prognosis in GC, while miR-194 predicted favorable prognosis in GC. We also provide the first comprehensive transcriptome analysis of miR-194 in GC. Our data suggest that miR-194 tends to regulate target genes by binding to their 3' UTRs in a 7-mer-A1, 7-mer-m8, or 8-mer manner. KEGG pathway analysis showed that the cell cycle was one of the pathways most affected by miR-194 in GC. Moreover, CCND1 was shown to be a novel target gene of miR-194 in GC. Additionally, downregulation of CCND1 by miR-194 in GC further led to cell growth inhibition and cell cycle arrest. In conclusion, miR-100, miR-125b, miR-199a, and miR-194 may have potential as prognostic and diagnostic biomarkers for GC. miR-194 suppresses GC cell growth mainly through targeting CCND1 and induction of cell cycle arrest.
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http://dx.doi.org/10.1002/2211-5463.13125DOI Listing
February 2021

Internal state configures olfactory behavior and early sensory processing in larvae.

Sci Adv 2021 Jan 1;7(1). Epub 2021 Jan 1.

Department of Physics, Harvard University, Cambridge, MA 02138, USA.

Animals exhibit different behavioral responses to the same sensory cue depending on their internal state at a given moment. How and where in the brain are sensory inputs combined with state information to select an appropriate behavior? Here, we investigate how food deprivation affects olfactory behavior in larvae. We find that certain odors repel well-fed animals but attract food-deprived animals and that feeding state flexibly alters neural processing in the first olfactory center, the antennal lobe. Hunger differentially modulates two output pathways required for opposing behavioral responses. Upon food deprivation, attraction-mediating uniglomerular projection neurons show elevated odor-evoked activity, whereas an aversion-mediating multiglomerular projection neuron receives odor-evoked inhibition. The switch between these two pathways is regulated by the lone serotonergic neuron in the antennal lobe, CSD. Our findings demonstrate how flexible behaviors can arise from state-dependent circuit dynamics in an early sensory processing center.
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http://dx.doi.org/10.1126/sciadv.abd6900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775770PMC
January 2021

Texture Analysis of F-FDG PET/CT for Differential Diagnosis Spinal Metastases.

Front Med (Lausanne) 2020 15;7:605746. Epub 2021 Jan 15.

Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

To evaluate the value of texture analysis for the differential diagnosis of spinal metastases and to improve the diagnostic performance of 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography/computed tomography (F-FDG PET/CT) for spinal metastases. This retrospective analysis of patients who underwent PET/CT between December 2015 and January 2020 at Shanghai Tenth People's Hospital due to high FDG uptake lesions in the spine included 45 cases of spinal metastases and 44 cases of benign high FDG uptake lesions in the spine. The patients were randomly divided into a training group of 65 and a test group of 24. Seventy-two PET texture features were extracted from each lesion, and the Mann-Whitney -test was used to screen the training set for texture parameters that differed between the two groups in the presence or absence of spinal metastases. Then, the diagnostic performance of the texture parameters was screened out by receiver operating characteristic (ROC) curve analysis. Texture parameters with higher area under the curve (AUC) values than maximum standardized uptake values (SUVmax) were selected to construct classification models using logistic regression, support vector machines, and decision trees. The probability output of the model with high classification accuracy in the training set was used to compare the diagnostic performance of the classification model and SUVmax using the ROC curve. For all patients with spinal metastases, survival analysis was performed using the Kaplan-Meier method and Cox regression. There were 51 texture parameters that differed meaningfully between benign and malignant lesions, of which four had higher AUC than SUVmax. The texture parameters were input to build a classification model using logistic regression, support vector machine, and decision tree. The accuracy of classification was 87.5, 83.34, and 75%, respectively. The accuracy of the manual diagnosis was 84.27%. Single-factor survival analysis using the Kaplan-Meier method showed that intensity was correlated with patient survival. Partial texture features showed higher diagnostic value for spinal metastases than SUVmax. The machine learning part of the model combined with the texture parameters was more accurate than manual diagnosis. Therefore, texture analysis may be useful to assist in the diagnosis of spinal metastases.
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http://dx.doi.org/10.3389/fmed.2020.605746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843930PMC
January 2021

G protein-coupled receptors: structure- and function-based drug discovery.

Signal Transduct Target Ther 2021 Jan 8;6(1). Epub 2021 Jan 8.

The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203, Shanghai, China.

As one of the most successful therapeutic target families, G protein-coupled receptors (GPCRs) have experienced a transformation from random ligand screening to knowledge-driven drug design. We are eye-witnessing tremendous progresses made recently in the understanding of their structure-function relationships that facilitated drug development at an unprecedented pace. This article intends to provide a comprehensive overview of this important field to a broader readership that shares some common interests in drug discovery.
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http://dx.doi.org/10.1038/s41392-020-00435-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790836PMC
January 2021

Psychometric evaluation of the DAILY EATS questionnaire in individuals living with obesity.

J Patient Rep Outcomes 2020 Nov 23;4(1):99. Epub 2020 Nov 23.

RTI Health Solutions, 3040 East Cornwallis Road, Post Office Box 12194, Research Triangle Park, NC, 27709-2194, USA.

Background: Physiological and behavioral factors including hunger, satiety, food intake, and cravings are health determinants contributing to obesity. Patient-reported outcome (PRO) measures focused on eating-related factors provide insight into the relationships between food choice and quantity, weight change, and weight-loss treatment for individuals living with obesity. The DAILY EATS is a novel 5-item, patient-reported measure evaluating key eating-related factors (Worst and Average Hunger, Appetite, Cravings, and Satiety).

Methods: Psychometric analyses, consistent with regulatory standards, were conducted to evaluate the DAILY EATS using data from two randomized trials that included individuals with severe obesity without diabetes (NCT03486392) and with severe obesity and type 2 diabetes (NCT03586830). Additional measures included Patient Global Impression of Status (PGIS) and Patient Global Impression of Change items, Impact of Weight on Quality of Life-Lite, Ease of Weight Management, and Patient-Reported Outcomes Measurement Information System Physical Function Short Form 8b and 10a. The reliability, validity, and responsiveness of the DAILY EATS were assessed, and a scoring algorithm and thresholds to interpret meaningful score changes were developed.

Results: Item-level analyses of the DAILY EATS supported computation of an Eating Drivers Index (EDI), comprising the related items Worst Hunger, Appetite, and Cravings. Internal consistency (Cronbach's coefficient alphas ≥0.80) and test-retest reliability (coefficients > 0.7) of the EDI were robust. Construct validity correlation patterns with other PRO measures were as hypothesized, with moderate to strong significant correlations between the EDI and PGIS-Hunger (0.30 ≤ r ≤ 0.68), PGIS-Cravings (0.33 ≤ r ≤ 0.77) and PGIS-Appetite (0.52 ≤ r ≤ 0.77). Anchor- and distribution-based analyses support reductions ranging from 1.6 to 2.1 as responder thresholds for the EDI, representing meaningful within-person improvement.

Conclusions: The DAILY EATS individual items and the composite EDI are reliable, sensitive, and valid in evaluating the concepts of hunger, appetite, and cravings for use in individuals with severe obesity with or without type 2 diabetes.
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http://dx.doi.org/10.1186/s41687-020-00259-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683653PMC
November 2020

Psychometric evaluation of the Nocturia Sleep Quality Scale based on data from a prospective observational study.

J Clin Sleep Med 2021 Apr;17(4):691-701

Ferring Pharmaceuticals A/S, Copenhagen, Denmark.

Study Objectives: The Nocturia Sleep Quality Scale (NSQS), a novel patient-reported outcomes measure, was developed to assess the impact of sleep disturbance from nocturia. The objective of this study was to assess the psychometric properties of the NSQS, including its structure, reliability, and validity.

Methods: Data were collected in the context of a web-based, prospective, longitudinal, observational study. Participants with nocturia were randomized 1:1 to either a group that received sleep hygiene instructions, including instructions to limit liquids at nighttime and empty bladder prior to bedtime, or one that did not receive sleep instructions. All participants were asked to provide responses to the web-based questionnaires from day 1 to day 10. Psychometric analyses, aligned with current regulatory guidance, were conducted to evaluate the daily scores and 3-day average scores of NSQS items and potential composites. Item-level analyses were conducted first, followed by composite-level analyses.

Results: The NSQS items and supporting measures demonstrated very slight improvement in patient-perceived sleep disturbance from nocturia over the course of the study. NSQS test-retest reliabilities were generally satisfactory. Correlations between NSQS items and related patient-reported measures tended to support the construct validity of the NSQS, and the known-groups analyses supplied evidence of its discriminating ability. NSQS responsiveness statistics were small.

Conclusions: The NSQS is a reliable and valid measure of the impact of nocturia on patients' sleep. The present analyses lay the psychometric groundwork for the use of the NSQS in future clinical trials to support product approval and labeling claims.
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http://dx.doi.org/10.5664/jcsm.9010DOI Listing
April 2021

TRADES: Targeted RNA Demethylation by SunTag System.

Adv Sci (Weinh) 2020 Oct 16;7(19):2001402. Epub 2020 Aug 16.

College of Chemistry and Molecular Sciences Wuhan University Wuhan 430072 China.

N6-methyladenosine (mA) is rapidly being studied and uncovered to play a significant role in various biological processes as well as in RNA fate and functions, while the effects of defined mA sites are rarely characterized for the lack of convenient tools. To provide an applicable method to remove mA modification at specific loci, an mA editing system called "targeted RNA demethylation by SunTag system (TRADES)" is engineered. In this system, the targeting element dCas13b is fused to ten copies of GCN4 peptides which can recruit multiple scFv-fusion RNA demethylase to demethylate the target mA site. Owing to this design, TRADES is more flexible to the indistinct mA sites for its wide editing window. By site-specific demethylation of messenger RNA (mRNA) SON A2699, the lifetime of SON RNA is successfully prolonged in HeLa cells. Meanwhile, TRADES negligibly influences the lifetime of other non-targeted transcripts. TRADES also can regulate the gene expression of target transcript in an mA-dependent manner. Moreover, the interference occuring for HBV and HIV replications demonstrates that the TRADES system holds potential in viral life cycle regulation and clinical applications.
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http://dx.doi.org/10.1002/advs.202001402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539198PMC
October 2020

4-Thiouridine-Enhanced Peroxidase-Generated Biotinylation of RNA.

Chembiochem 2021 Jan 20;22(1):212-216. Epub 2020 Oct 20.

College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University, Wuhan, Hubei, 430072, P. R. China.

Peroxidase-generated proximity labeling is in widespread use to study subcellular proteomes and the protein interaction networks in living cells, but the development of subcellular RNA labeling is limited. APEX-seq has emerged as a new method to study subcellular RNA in living cells, but the labeling of RNA still has room to improve. In this work, we describe 4-thiouridine (s U)-enhanced peroxidase-generated biotinylation of RNA with high efficiency. The incorporation of s U could introduce additional sites for RNA labeling, enhanced biotinylation was observed on monomer, model oligo RNA and total RNA. Through the s U metabolic approach, the in vivo RNA biotinylation efficiency by peroxidase catalysis was also dramatically increased, which will benefit RNA isolation and study for the spatial transcriptome.
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http://dx.doi.org/10.1002/cbic.202000567DOI Listing
January 2021

Discovering Biomarkers in Peritoneal Metastasis of Gastric Cancer by Metabolomics.

Onco Targets Ther 2020 27;13:7199-7211. Epub 2020 Jul 27.

Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, Jilin Province 130000, People's Republic of China.

Background And Objective: Metabolomics has recently been applied in the field of oncology. In this study, we aimed to use metabolomics to explore biomarkers in peritoneal metastasis of gastric cancer.

Methods: Peritoneal lavage fluid (PLF) of 65 gastric cancer patients and related clinical data were collected from the First Hospital of Jilin University. The metabolic components were identified by liquid chromatography-mass spectrometry (LC-MS). Total ion current (TIC) spectra, principal component analysis (PCA), and the Student's -test were used to identify differential metabolites in PLF. A support vector machine (SVM) was used to screen the differential metabolites in PLF with a weight of 100%. Cluster analysis was used to evaluate the similarity between samples. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic ability of the metabolites. Univariate and multivariate logistic regression analyses were used to identify potential risk factors for peritoneal metastasis of gastric cancer.

Results: We found the differential levels of PLF metabolites by LC-MS, TIC spectra, PCA and the -test. Cluster analysis showed the co-occurrence of metabolites in the peritoneal metastasis group (p<0.05). ROC analysis showed the diagnostic ability of metabolites (p<0.05). Univariate and multivariate logistic regression analyses showed the potential independent risk factors for peritoneal metastasis in gastric cancer patients (p<0.05).

Conclusion: Through the statistical analysis of metabolomics, we found that TG (54:2), G3P, α-aminobutyric acid, α-CEHC, dodecanol, glutamyl alanine, 3-methylalanine, sulfite, CL (63:4), PE-NMe (40:5), TG (53:4), retinol, 3-hydroxysterol, tetradecanoic acid, MG (21:0/0:0/0:0), tridecanoic acid, myristate glycine and octacosanoic acid may be biomarkers for peritoneal metastasis of gastric cancer.
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http://dx.doi.org/10.2147/OTT.S245663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394602PMC
July 2020

Identification of metastasis and prognosis-associated genes for serous ovarian cancer.

Biosci Rep 2020 06;40(6)

Department of Obstetrics and Gynecology, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, China.

Serous ovarian cancer is one of the most fatal gynecological tumors with an extremely low 5-year survival rate. Most patients are diagnosed at an advanced stage with wide metastasis. The dysregulation of genes serves an important role in the metastasis progression of ovarian cancer. Differentially expressed genes (DEGs) between primary tumors and metastases of serous ovarian cancer were screened out in the gene expression profile of GSE73168 from Gene Expression Omnibus (GEO). Cytoscape plugin cytoHubba and weighted gene co-expression network analysis (WGCNA) were utilized to select hub genes. Univariate and multivariate Cox regression analyses were used to screen out prognosis-associated genes. Furthermore, the Oncomine validation, prognostic analysis, methylation mechanism, gene set enrichment analysis (GSEA), TIMER database analysis and administration of candidate molecular drugs were conducted for hub genes. Nine hundred and fifty-seven DEGs were identified in the gene expression profile of GSE73168. After using Cytoscape plugin cytoHubba, 83 genes were verified. In co-expression network, the blue module was most closely related to tumor metastasis. Furthermore, the genes in Cytoscape were analyzed, showing that the blue module and screened 17 genes were closely associated with tumor metastasis. Univariate and multivariate Cox regression revealed that the age, stage and STMN2 were independent prognostic factors. The Cancer Genome Atlas (TCGA) suggested that the up-regulated expression of STMN2 was related to poor prognosis of ovarian cancer. Thus, STMN2 was considered as a new key gene after expression validation, survival analysis and TIMER database validation. GSEA confirmed that STMN2 was probably involved in ECM receptor interaction, focal adhesion, TGF beta signaling pathway and MAPK signaling pathway. Furthermore, three candidate small molecule drugs for tumor metastasis (diprophylline, valinomycin and anisomycin) were screened out. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot showed that STMN2 was highly expressed in ovarian cancer tissue and ovarian cancer cell lines. Further studies are needed to investigate these prognosis-associated genes for new therapy target.
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http://dx.doi.org/10.1042/BSR20194324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317593PMC
June 2020

The Prediction and Prognostic Significance of INPP5K Expression in Patients with Liver Cancer.

Biomed Res Int 2020 25;2020:9519235. Epub 2020 Apr 25.

Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China.

Liver cancer is a devastating disease for humans with poor prognosis. Although the survival rate of patients with liver cancer has improved in the past decades, the recurrence and metastasis of liver cancer are still obstacles for us. Inositol polyphosphate-5-phosphatase K (INPP5K) belongs to the family of phosphoinositide 5-phosphatases (PI 5-phosphatases), which have been reported to be associated with cell migration, polarity, adhesion, and cell invasion, especially in cancers. However, there have been few studies on the correlation of INPP5K and liver cancer. In this study, we explored the prognostic significance of INPP5K in liver cancer through bioinformatics analysis of data collected from The Cancer Genome Atlas (TCGA) database. Chi-square and Fisher exact tests were used to evaluate the relationship between INPP5K expression and clinical characteristics. Our results showed that low INPP5K expression was correlated with poor outcomes in liver cancer patients. Univariate and multivariate Cox analyses demonstrated that low INPP5K mRNA expression played a significant role in shortening overall survival (OS) and relapse-free survival (RFS), which might serve as the useful biomarker and prognostic factor for liver cancer. In conclusion, low INPP5K mRNA expression is an independent risk factor for poor prognosis in liver cancer.
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http://dx.doi.org/10.1155/2020/9519235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201693PMC
February 2021

Hormone receptor expression correlates with EGFR gene mutation in lung cancer in patients with simultaneous primary breast cancer.

Transl Lung Cancer Res 2020 Apr;9(2):325-336

Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Background: The coexistence of double primaries of lung cancer (LC) and breast cancer (BC) are not uncommon in women, but there has been limited research conducted of their molecular association. To decipher the internal pathogenesis of LC in patients with concurrent BC and LC, this study explored the clinical factors and relationship between hormone receptor (HR) expression and epidermal growth factor receptor (EGFR) gene mutation.

Methods: The clinicopathological characteristics of 400 female patients clinically diagnosed with double primary LC and BC at Fudan University Shanghai Cancer Center were collected. Pathological discrimination was performed to further confirm the double primaries in patients with available tissues. LC samples were then examined to detect EGFR gene mutation status by PCR-based assays and HR expression by immunohistochemistry (IHC). As a control cohort, the characteristics of 114 consecutive patients with LC only were compared with the double-primary patient group.

Results: A total of 169 patients were pathologically confirmed with simultaneous LC and BC between January 2010 and October 2018. The dominant LC subtype was adenocarcinoma (ADC) (95.1%), and invasive ductal carcinoma (IDC) was the main BC subtype (71.0%). Synchronous and metachronous double primary BC-LC cases accounted for 39.1% and 60.9% of the patients, respectively. The absence of family cancer history was associated with a shorter interval between the two primary cancer diagnoses. Among 64 patients with EGFR mutations, 34.4% had HR-positive LC tissue, compared with 0/24 (0%) of those with EGFR wild-type LC (P<0.001). All of the patients with positive HR expression harbored an activating EGFR mutation (n=22); however, no correlation was observed in the control cohort.

Conclusions: Double primary BC-LC patients have distinctive clinicopathological features compared to those with LC only. The expression of HRs is significantly correlated with EGFR mutation status of LC tissues.
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http://dx.doi.org/10.21037/tlcr-20-513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225161PMC
April 2020

Sex differences in the proliferation of pulmonary artery endothelial cells: implications for plexiform arteriopathy.

J Cell Sci 2020 05 14;133(9). Epub 2020 May 14.

Department of Internal Medicine, Pulmonary, Critical Care and Sleep Medicine, Rush University Medical Center, Chicago, IL 60612, USA

The sex-biased disease pulmonary arterial hypertension (PAH) is characterized by the proliferation and overgrowth of dysfunctional pulmonary artery endothelial cells (PAECs). During inflammation associated with PAH, granzyme B cleaves intersectin-1 to produce N-terminal (EH) and C-terminal (SH3A-E) protein fragments. In a murine model of PAH, EH triggers plexiform arteriopathy via p38-ELK1-c-Fos signaling. The SH3A-E fragment also influences signaling, having dominant-negative effects on ERK1 and ERK2 (also known as MAPK3 and MAPK1, respectively). Using PAECs engineered to express tagged versions of EH and SH3A-E, we demonstrate that the two ITSN fragments increase both p38-ELK1 activation and the ratio of p38 to ERK1 and ERK2 activity, leading to PAEC proliferation, with female cells being more responsive than male cells. Furthermore, expression of EH substantially upregulates the expression and activity of the long non-coding RNA in female PAECs, which in turn upregulates the X-linked gene and represses expression of (). These events are recapitulated by the PAECs of female idiopathic PAH patients, and may account for their proliferative phenotype. Thus, upregulation of could be an important factor in explaining sexual dimorphism in the proliferative response of PAECs and the imbalanced sex ratio of PAH.
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http://dx.doi.org/10.1242/jcs.237776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240306PMC
May 2020

Ubiquitin-like modifier-activating enzyme 7 as a marker for the diagnosis and prognosis of breast cancer.

Oncol Lett 2020 Apr 17;19(4):2773-2784. Epub 2020 Feb 17.

Cardiovascular Center, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

Ubiquitin-like modifier-activating enzyme 7 (UBA7) is a specific E1-like ubiquitin-activating enzyme involved in interferon-stimulated gene 15 (ISG15) conjugation. UBA7 expression has been reported to be notably decreased in lung cancer. The present study aimed to investigate the changes in UBA7 expression in breast cancer and the association between UBA7 expression and clinical characteristics, and to elucidate the diagnostic and prognostic significance of UBA7 in breast cancer. The clinical data and RNA-sequencing expression values of 1,104 patients with breast cancer were downloaded from The Cancer Genome Atlas database. The associations between UBA7 expression and clinical characteristics were determined using χ and Fisher's exact tests. UBA7 expression values were divided into low and high groups using the optimal cut-off value, as determined by the overall survival (OS) value identified via a receiver operating characteristic (ROC) curve analysis, to further study the association between UBA7 expression and clinical characteristics. The diagnostic capability of UBA7 was assessed via ROC analysis, and Kaplan-Meier curve and Cox regression analyses were performed to determine the prognostic value of UBA7. The results demonstrated that UBA7 expression was decreased in breast cancer, and significant differences were observed between groups with regards to vital status, tumor classification, metastasis classification, histological type, sex, molecular subtype, and expression levels of progesterone receptor, estrogen receptor (ER) and human epidermal growth factor receptor 2. Low and high UBA7 expression levels were associated with age, ER expression, menopause status, Tumor-Node-Metastasis classification stage, margin status, vital status, radiation therapy use, OS and relapse-free survival. Furthermore, patients with low UBA7 expression levels had a poor prognosis. UBA7 expression also demonstrated an ability to diagnose patients at all clinical stages. Taken together, the results indicated that UBA7 expression was significantly decreased in breast cancer, and was associated with clinical characteristics and prognosis. Thus, UBA7 can be deemed as a potential biomarker in breast cancer, and may serve as a target in treatment.
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http://dx.doi.org/10.3892/ol.2020.11406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068442PMC
April 2020

Corrigendum to "TRPM8 activation improves energy expenditure in skeletal muscle and exercise endurance in mice" [Gene 641 (2018) 111-116].

Gene 2020 04 18;735:144392. Epub 2020 Feb 18.

Laboratory of Medicinal Plant, School of Basic Medicine, Hubei University of Medicine, Shiyan 442000, China. Electronic address:

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http://dx.doi.org/10.1016/j.gene.2020.144392DOI Listing
April 2020

Rapamycin inhibits B-cell activating factor (BAFF)-stimulated cell proliferation and survival by suppressing Ca-CaMKII-dependent PTEN/Akt-Erk1/2 signaling pathway in normal and neoplastic B-lymphoid cells.

Cell Calcium 2020 05 7;87:102171. Epub 2020 Feb 7.

Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, PR China. Electronic address:

B-cell activating factor (BAFF) is a crucial survival factor for B cells, and excess BAFF contributes to development of autoimmune diseases. Recent studies have shown that rapamycin can prevent BAFF-induced B-cell proliferation and survival, but the underlying mechanism remains to be elucidated. Here we found that rapamycin inhibited human soluble BAFF (hsBAFF)-stimulated cell proliferation by inducing G-cell cycle arrest, which was through downregulating the protein levels of CDK2, CDK4, CDK6, cyclin A, cyclin D1, and cyclin E. Rapamycin reduced hsBAFF-stimulated cell survival by downregulating the levels of anti-apoptotic proteins (Mcl-1, Bcl-2, Bcl-xL and survivin) and meanwhile upregulating the levels of pro-apoptotic proteins (BAK and BAX). The cytostatic and cytotoxic effects of rapamycin linked to its attenuation of hsBAFF-elevated intracellular free Ca ([Ca]). In addition, rapamycin blocked hsBAFF-stimulated B-cell proliferation and survival by preventing hsBAFF from inactivating PTEN and activating the Akt-Erk1/2 pathway. Overexpression of wild type PTEN or ectopic expression of dominant negative Akt potentiated rapamycin's suppression of hsBAFF-induced Erk1/2 activation and proliferation/viability in Raji cells. Interestingly, PP242 (mTORC1/2 inhibitor) or Akt inhibitor X, like rapamycin (mTORC1 inhibitor), reduced the basal or hsBAFF-induced [Ca] elevations. Chelating [Ca] with BAPTA/AM, preventing [Ca] elevation using EGTA, 2-APB or verapamil, inhibiting CaMKII with KN93, or silencing CaMKII strengthened rapamycin's inhibitory effects. The results indicate that rapamycin inhibits BAFF-stimulated B-cell proliferation and survival by blunting mTORC1/2-mediated [Ca] elevations and suppressing Ca-CaMKII-dependent PTEN/Akt-Erk1/2 signaling pathway. Our finding underscores that rapamycin may be exploited for prevention of excessive BAFF-induced aggressive B-cell malignancies and autoimmune diseases.
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http://dx.doi.org/10.1016/j.ceca.2020.102171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168758PMC
May 2020

Ion Gel Capacitively Coupled Tribotronic Gating for Multiparameter Distance Sensing.

ACS Nano 2020 Mar 20;14(3):3461-3468. Epub 2020 Feb 20.

Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 100083, China.

Developing sophisticated device architectures is of great significance to go beyond Moore's law with versatility toward human-machine interaction and artificial intelligence. Tribotronics/tribo-iontronics offer a direct way to controlling the transport properties of semiconductor devices by mechanical actions, which fundamentally relies on how to enhance the tribotronic gating effect through device engineering. Here, we propose a universal method to enhance the tribotronic properties through electric double layer (EDL) capacitive coupling. By preparing an ion gel layer on top of tribotronic graphene transistor, we demonstrate a dual-mode field effect transistor (, a tribotronic transistor with capacitively coupled ion gel and an ion-gel-gated graphene transistor with a second tribotronic gate). The resulted tribotronic gating performances are greatly improved by twice for the on-state current and four times for the on/off ratio (the first mode). It can also be utilized as a multiparameter distance sensor with drain current increased by ∼600 μA and threshold voltage shifted by ∼0.8 V under a mechanical displacement of 0.25 mm (the second mode). The proposed methodology of EDL capacitive coupling offers a facile and efficient way to designing more sophisticated tribotronic devices with superior performance and multifunctional sensations.
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http://dx.doi.org/10.1021/acsnano.9b09549DOI Listing
March 2020

Evaluation of chemical cross-linkers for in-depth structural analysis of G protein-coupled receptors through cross-linking mass spectrometry.

Anal Chim Acta 2020 Mar 19;1102:53-62. Epub 2019 Dec 19.

iHuman Institute, ShanghaiTech University, 201210, Shanghai, China; School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China. Electronic address:

Chemical cross-linking would conceivably cause structural disruption of a protein, but few cross-linkers have been fully evaluated in this aspect. Furthermore, integral membrane proteins may differ from soluble proteins in the selection of suitable cross-linkers, which has never been investigated. In this study, we systematically evaluated the impact of five conventional cross-linkers targeting Lys, Asp and Glu, and two Arg-reactive cross-linkers on the structural and functional integrity of two G protein-coupled receptors (GPCRs). Perturbation of the receptor structure and ligand-binding activity was observed, depending on the receptor and cross-linking conditions. In particular, our study demonstrated that the concentrations of PDH and KArGO need to be fine-tuned in order to minimize the structural and functional disturbance of specific GPCRs. A set of amenable cross-linkers was selected to acquire the most comprehensive cross-link maps for two GPCRs. Our in-depth cross-linking mass spectrometry (CXMS) analysis has revealed dynamic features of structural regions in GPCRs that are not observable in the crystal structures. Thus, CXMS analysis of GPCRs using the expanded toolkit would facilitate structural modeling of uncharacterized receptors and gain new insights into receptor-ligand interactions.
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http://dx.doi.org/10.1016/j.aca.2019.12.036DOI Listing
March 2020

Microcystis aeruginosa affects the inducible anti-predator responses of Ceriodaphnia cornuta.

Environ Pollut 2020 Apr 8;259:113952. Epub 2020 Jan 8.

Jiangsu Key Laboratory for Biodiversity and Biotechnology, School of Biological Sciences, Nanjing Normal University, 1 Wenyuan Road, Nanjing, 210023, China. Electronic address:

Cyanobacterial blooms are an increasing problem in a more eutrophic world. It is still a challenge to fully understand the influence of cyanobacteria on the interactions between predator and prey at higher trophic levels. The present study was mainly undertaken to understand the inducible anti-predator responses of cladocerans while using cyanobacteria as part of food. Specifically speaking, we focused on the anti-predator strategies of Ceriodaphnia cornuta in response to different predators (fish and Chaoborus larvae) under food with different proportions of Microcystis aeruginosa. The morphological (i.e., body size and the induction of horns) and life history traits (e.g., time to first reproduction, offspring number, and survival time) responses were measured under different proportions of M. aeruginosa (i.e., 0%, 20%, 40%, 60%, 80%, and 100%). Our results showed that both the life history and the inducible anti-predator responses of C. cornuta were significantly affected by different concentrations of M. aeruginosa. Specifically, lower concentrations of Microcystis (20%-60%) can significantly promote the horns induction under Chaoborus predation risks, and higher Microcystis concentrations (60%-100%) tend to enhance reproduction in response to fish predation risks, such as larger body size, decreased time to first reproduction, and increased total offspring number. Additionally, an increasing concentration of M. aeruginosa decreased the ability of C. cornuta to reverse horns when predation risks removed. Our findings indicated that cyanobacteria affecting life history traits and the subsequent indirect effects on anti-predator responses in cladocerans could impact the interactions between predator and prey at higher trophic levels and may consequently contribute to shaping the structure of the community in a cyanobacteria bloom area.
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http://dx.doi.org/10.1016/j.envpol.2020.113952DOI Listing
April 2020

Left ventricular mechanical dyssynchrony assessment in obese patients using the cadmium-zinc telluride SPECT camera.

Int J Cardiovasc Imaging 2020 Apr 9;36(4):757-765. Epub 2020 Jan 9.

Department of Nuclear Medicine, Shanghai Tenth People's Hospital of Tongji University, Yanchang RD. 301, Shanghai, 200072, People's Republic of China.

The use of phase analysis techniques to assess left ventricular mechanical dyssynchrony (LVMD) has been well documented. However, artifacts have reduced the accuracy of the assessment due to soft tissue attenuation, so little information is available about the effects of obesity on LVMD. The aim of this study was to evaluate LVMD in patients with simple obesity by SPECT with a new cadmium-zinc telluride (CZT) detector and to explore the effects of obesity on left ventricular wall motion. We retrospectively analyzed 95 patients with myocardial perfusion imaging (MPI) images without perfusion defects, of which 55 were diagnosed with simple obesity (BMI > 30), and 40 non-obese patients (BMI < 25) matched for age and sex were used as controls. The five-point method was used to analyze the MPI images of the two groups, and the complete cardiac function parameters including phase bandwidth (PBW) and phase standard deviation (PSD) were obtained. Although the PBW values of the two groups were within the normal range (cut-off value > 90°), the PBW (35.4 ± 28 vs 24.9 ± 7.5, P < .001; 36.6 ± 18.4 vs 28.7 ± 9.1, P = 0.01) and PSD (8.7 ± 7.6 vs 5.9 ± 2, P = 0.02; 9.2 ± 4.9 vs 7.1 ± 2.7, P = 0.01) of the obese group were larger than the control group under both stressing and resting, and the difference was statistically significant. CZT-SPECT can effectively assess LVMD in obese patients, and they are more likely to develop LVMD, which may be related to their left ventricular volume.
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http://dx.doi.org/10.1007/s10554-019-01762-yDOI Listing
April 2020

LncRNA MAGI2-AS3 Is Regulated by BRD4 and Promotes Gastric Cancer Progression via Maintaining ZEB1 Overexpression by Sponging miR-141/200a.

Mol Ther Nucleic Acids 2020 Mar 15;19:109-123. Epub 2019 Nov 15.

School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China; School of Biomedical Engineering, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China; Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China. Electronic address:

Long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis and tumor progression. However, the biological function of most lncRNAs remains unknown in human gastric cancer. This study here aims to explore the unknown function of lncRNA MAGI2-AS3 in gastric cancer. First, bioinformatics analysis showed that lncRNA MAGI2-AS3 was overexpressed in gastric cancer tissues, and the overexpression of MAGI2-AS3 has been shown to be associated with poor prognosis in all three independent gastric cancer cohorts (The Cancer Genome Atlas stomach cancer [TCGA_STAD], GEO: GSE62254 and GSE15459). The multivariate analysis indicated that lncRNA MAGI2-AS3 was an independent prognostic factor for both overall survival and disease-free survival of gastric cancer patients. Moreover, MAGI2-AS3 was identified to be an epithelial-mesenchymal transition (EMT)-related lncRNA and was highly co-expressed with ZEB1/2 in both gastric cancer tissues and normal stomach tissues. Loss-of-function and gain-of-function studies showed that lncRNA MAGI2-AS3 could positively regulate ZEB1 expression and the process of cell migration and invasion in gastric cancer. Subcellular location assay showed that lncRNA MAGI2-AS3 was mainly located in the cytoplasm of gastric cancer cells. Bioinformatics analysis and functional experiments revealed that lncRNA MAGI2-AS3 was negatively correlated with miR-141/200a expression and negatively regulated miR-141/200a-3p expression in gastric cancer. Therefore, we speculate that lncRNA MAGI2-AS3 promotes tumor progression through sponging miR-141/200a and maintaining overexpression of ZEB1 in gastric cancer. Nevertheless, we identified that BRD4 is a transcriptional regulator of lncRNA MAGI2-AS3 in gastric cancer. Additionally, our findings highlight that lncRNA MAGI2-AS3 is an ideal biomarker and could be a potential therapeutic target for gastric cancer.
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http://dx.doi.org/10.1016/j.omtn.2019.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920306PMC
March 2020

Expression and potential prognostic value of histone family gene signature in breast cancer.

Exp Ther Med 2019 Dec 25;18(6):4893-4903. Epub 2019 Oct 25.

Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.

Breast cancer (BC) is the most common type of malignancy among females worldwide. Histone modifications, which are the major post-translational modifications, have a significant role in cancer development and prognosis. However, whether histone family genes may serve as potential prognostic biomarkers for BC patients has remained elusive. In the present study, RNA-sequencing data were obtained from The Cancer Genome Atlas (TCGA). Differentially expressed genes were identified and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway functional enrichment analysis was performed. As histone family genes have been reported to be associated with cervical cancer, the present study hypothesized that histone family genes are associated with gynecological tumors. Histone family genes, including histone cluster 1 H1A family member B and , were upregulated and identified as hub genes in the protein-protein interaction network. In addition, Oncomine and the Human Protein Atlas were used to further verify the expression levels of histone gene sets. The PrognoScan database was then used to investigate the association between expression and prognostic value regarding cancer patient survival. The present results indicated that higher expression of histone gene sets was associated with poor overall survival, relapse-free survival and distant metastasis-free survival of BC patients. The differential expression of histone family genes between BC and normal samples was validated by reverse transcription-quantitative PCR. Finally, to determine the clinical role of histone family genes in BC, the correlations between histone family genes expression and clinical characteristics were investigated through data collected from TCGA. Therefore, the present study indicates that histone gene sets may be used as prognostic factors for survival prediction for BC patients.
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http://dx.doi.org/10.3892/etm.2019.8131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861870PMC
December 2019

Responder Threshold for Patient-Oriented Eczema Measure (POEM) and Children's Dermatology Life Quality Index (CDLQI) in Adolescents with Atopic Dermatitis.

Dermatol Ther (Heidelb) 2019 Dec 22;9(4):799-805. Epub 2019 Oct 22.

Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.

Introduction: The Patient-Oriented Eczema Measure (POEM) assesses patient-reported frequency of atopic dermatitis (AD) symptoms, while the Children's Dermatology Life Quality Index (CDLQI) measures the impact of skin disease on health-related quality of life (HRQoL) in children. There is currently no threshold for clinically meaningful within-person change in POEM or CDLQI scores in adolescents. Here we empirically derive within-person thresholds of meaningful within-person change in POEM and CDLQI scores in adolescents with moderate-to-severe AD.

Methods: Data were used from a phase 3, randomized, double-blind, placebo-controlled trial of dupilumab in adolescents (aged ≥ 12 to < 18 years) with moderate-to-severe AD. Anchor-based methods were employed using the mean change in POEM and CDLQI scores from baseline to week 16 linked with a 1-point improvement in Patient Global Assessment of Disease (PGAD), a score of "a little better" on the Patient Global Assessment of Treatment effect (PGAT), a 50-74% improvement from baseline in the Eczema Area and Severity Index (EASI-50-74), and a 1-point improvement in Investigator's Global Assessment (IGA) score.

Results: A mean change of - 7.8 and - 5.6 in the POEM score was associated with PGAD and PGAT anchors, respectively. EASI-50-74 was associated with a mean change in POEM score of - 8.2, while the IGA anchor was associated with a mean change of - 7.9 in POEM score. The mean changes in CDLQI score associated with PGAD and PGAT anchors were - 6.4 and - 6.6, respectively, while CDLQI mean scores changed by - 8.3 and - 8.0 for the EASI and IGA anchors, respectively.

Conclusion: In adolescents (aged ≥ 12 to < 18 years) with moderate-to-severe AD, a within-person change of 6-8 points in POEM and CDLQI scores, independently, can be considered a reasonable responder threshold for clinically meaningful change in each of the two scales, respectively.

Trial Registration: ClinicalTrials.gov Identifier: NCT03054428.

Funding: Sanofi and Regeneron Pharmaceuticals, Inc.
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http://dx.doi.org/10.1007/s13555-019-00333-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828922PMC
December 2019

MiR-200a-3p promoted the malignant behaviors of ovarian cancer cells through regulating PCDH9.

Onco Targets Ther 2019 8;12:8329-8338. Epub 2019 Oct 8.

Department of Obstetrics and Gynecology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, People's Republic of China.

Background: Increasing evidence has revealed that the aberrant expression of microRNAs (miRNAs) plays vital roles in the development and progression of ovarian cancer. MiR-200a-3p was found to act as an oncogene in a variety of cancers, however, the expression and function of miR-200a-3p in ovarian cancer has not been characterized.

Materials And Methods: The expression of miR-200a-3p in ovarian cancer tissues and cell lines was detected by the RT-qPCR. The influence of miR-200a-3p on the growth of ovarian cancer cells was determined with the Cell Counting Kit-8 assay, colony formation and cell invasion assay. The binding of miR-200a-3p with the 3'-untranslated region (UTR) of PDCH9 was detected by luciferase reporter assay. The expression of PCDH9 was investigated by RT-qPCR and Western blot analysis.

Results: miR-200a-3p was up-regulated in ovarian cancer tissues and cell lines. Highly expressed miR-200a-3p was significantly associated with the tumor size, tumor metastasis and TNM stage. Overexpression of miR-200a-3p markedly promoted the proliferation, colony formation and invasion of ovarian cancer cells. Functional study uncovered that miR-200a-3p bound the 3'-untranslated region (UTR) of PCDH9 and decreased the expression of PCDH9 in ovarian cancer cells. The expression of miR-200a-3p in ovarian cancer tissues was significantly negatively correlated with that of PCDH9. Restored PCDH9 inhibited the promoting effect of miR-200a-3p on the proliferation of ovarian cancer cells.

Conclusion: Our results suggested the potential oncogenic function of miR-200a-3p via modulating PCDH9 in ovarian cancer.
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http://dx.doi.org/10.2147/OTT.S220339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790212PMC
October 2019

Optimal compressed sensing strategies for an array of nonlinear olfactory receptor neurons with and without spontaneous activity.

Proc Natl Acad Sci U S A 2019 10 23;116(41):20286-20295. Epub 2019 Sep 23.

Physical Sciences Department, IBM T. J. Watson Research Center, Yorktown Heights, NY 10598

There are numerous different odorant molecules in nature but only a relatively small number of olfactory receptor neurons (ORNs) in brains. This "compressed sensing" challenge is compounded by the constraint that ORNs are nonlinear sensors with a finite dynamic range. Here, we investigate possible optimal olfactory coding strategies by maximizing mutual information between odor mixtures and ORNs' responses with respect to the bipartite odor-receptor interaction network (ORIN) characterized by sensitivities between all odorant-ORN pairs. For ORNs without spontaneous (basal) activity, we find that the optimal ORIN is sparse-a finite fraction of sensitives are zero, and the nonzero sensitivities follow a broad distribution that depends on the odor statistics. We show analytically that sparsity in the optimal ORIN originates from a trade-off between the broad tuning of ORNs and possible interference. Furthermore, we show that the optimal ORIN enhances performances of downstream learning tasks (reconstruction and classification). For ORNs with a finite basal activity, we find that having inhibitory odor-receptor interactions increases the coding capacity and the fraction of inhibitory interactions increases with the ORN basal activity. We argue that basal activities in sensory receptors in different organisms are due to the trade-off between the increase in coding capacity and the cost of maintaining the spontaneous basal activity. Our theoretical findings are consistent with existing experiments and predictions are made to further test our theory. The optimal coding model provides a unifying framework to understand the peripheral olfactory systems across different organisms.
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http://dx.doi.org/10.1073/pnas.1906571116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789560PMC
October 2019

Alter circulating cell-free DNA variables in plasma of ovarian cancer patients.

J Obstet Gynaecol Res 2019 Nov 9;45(11):2237-2242. Epub 2019 Sep 9.

Department of Obstetrics and Gynecology, The Affiliated Huaian No.1 People's Hospital, Nanjing Medical University, Huai'an, China.

Aim: Liquid biopsy shows great potential in the fields of early diagnosis and prognosis in cancer. Ovarian cancer (OC) is the seventh most common cancer and the eighth most common cause of death from cancer in women. The early diagnosis of OC is vital for subsequent treatment and outcome. Here we investigated two markers: cell-free DNA concentration (cfDNA conc) and cell-free DNA integrity (cfDI) between OC patients and healthy controls.

Methods: Age-matched OC patients and healthy controls were enrolled in this study. In total, there are 20 patients and 20 healthy controls. cfDNA conc and cfDI were calculated by arthrobacter luteus (ALU) gene using quantitative real-time polymerase chain reaction (PCR).

Results: An increased cfDNA conc in OC patients compared to healthy controls was observed (mean cfDNA conc for OC patients: 1.98 ng/μL, for healthy control: 0.51 ng/μL, P = 0.02). For cfDI, the median value of OC patients is 0.49 while the median value of healthy control is 0.61 (P = 0.038). The diagnostic value of area under the curve was 0.86 for cfDNA conc and 0.72 for cfDI. When cfDNA conc and cfDI were combined, the diagnostic value was 0.90 which indicates a good diagnostic marker.

Conclusion: As few reports of cfDNA conc and cfDI differences between OC patients and healthy controls reported, our study shows increased cfDNA concentrations and decreased cfDI in OC patients compared to healthy controls. We also propose that cfDNA biomarkers can be potential diagnostic markers in ovarian cancer.
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http://dx.doi.org/10.1111/jog.14102DOI Listing
November 2019

The expression and clinical significance of secretory leukocyte proteinase inhibitor (SLPI) in mammary carcinoma using bioinformatics analysis.

Gene 2019 Dec 30;720:144088. Epub 2019 Aug 30.

Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address:

Background: Secretory leukocyte protease inhibitor (SPLI) was a secreted protein which belongs to a member of whey acidic protein four-disulfide core family. In breast cancer (BC) it may inhibit cell proliferation and promote cancer metastasis. In this study, a comprehensive bioinformatics analysis was performed to identify the expression and prognostic value of SLPI in breast cancer.

Methods: SLPI expression in breast cancer was analyzed in Oncomine online database, which was subsequently confirmed by quantitative PCR (qPCR) in 18 BC samples and western blotting in 26 BC samples. Breast cancer gene-expression miner v4.1 was used to access the expression level with clinicopathological parameters in breast cancer patients. The prognostic values of SLPI in breast cancer were evaluated using the PrognoScan database.

Results: Our results indicated that SLPI was downregulated in breast cancer than in normal tissues. SLPI expression was found to be negatively correlated with estrogen receptor (ER) and progesterone receptor (PR) status. SLPI expression level was decreased in negative basal-like status patients compared with positive basal-like status. Meanwhile, triple-negative breast cancer status positive correlated with SLPI. We confirmed a positive correlation between SLPI and interleukin 17 receptor B (IL17RB) express in breast cancer tissues via oncomine co-expression analysis. Ten proteins: Elastase, Granulin, Lipocalin, Defensin beta 103B, Defensin beta 103A, Tubulin, Heparin-binding EGF-like growth factor, Interleukin 6, Epidermal growth factor, Phospholipid scramblase 1 were determinate interactions with SLPI by STRING.

Conclusion: SLPI could as a biomarker to predict the prognosis values of breast cancer. However, further comprehensive study and mining more evidence are needed to clarify our results.
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http://dx.doi.org/10.1016/j.gene.2019.144088DOI Listing
December 2019