Cosmetics, Vol. 5, Pages 35: From Mice to Men: An Evolutionary Conserved Breakdown of the Epidermal Calcium Gradient and Its Impact on the Cornified Envelope

Cosmetics, Vol. 5, Pages 35: From Mice to Men: An Evolutionary Conserved Breakdown of the Epidermal Calcium Gradient and Its Impact on the Cornified Envelope

Cosmetics doi: 10.3390/cosmetics5020035

Authors: Maria Karolin Streubel Claudia Neuhofer Johannes Bischof Peter Steinbacher Elisabeth Russe Gottfried Wechselberger Klaus Richter Mark Rinnerthaler

In previous publications, we could establish that a hallmark of human skin aging is the breakdown of the epidermal calcium gradient. This redistribution of calcium has many implications, including a restructuring of the cornified envelope, a reduced epidermal barrier function, a change in lipid composition, a reduced skin hydration, and an increased skin pH. Especially the age-dependent change in the cornified envelope composition was solely studied in human foreskin samples. The aim of this study was to confirm that this effect is neither restricted to UV-protected skin area nor limited to a specific sex. In addition, we wanted to show that the collapse of the epidermal calcium gradient is not only a hallmark of human skin aging, but is also evolutionarily conserved in mammals. By using such techniques as IHC, Western blot analysis, and RT-PCR, we could demonstrate the following: (1) A change in the epidermal calcium gradient is in fact the most important sign of epidermal aging in mammals (as shown in female human eyelids and mouse skin samples of the external ear-shell); (2) The disturbed calcium homeostasis affects the expression and crosslinking of most cornified-envelope-specific genes such as loricrin and filaggrin. In this way, we could establish that the age-dependent altered composition of the cornified envelope is a typical sign of skin aging not only in humans, but in mice, too. This makes the mouse an important model organism to study these changes.

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Retraction notice to "Graphene quantum dots decorated CdS doped graphene oxide sheets in dual action mode: as initiator and platform for designing of nimesulide imprinted polymer " [BIOS 89P1 (2017) 627-635]

Publication date: 30 August 2018
Source:Biosensors and Bioelectronics, Volume 114
Author(s): Santanu Patra, Ekta Roy, Raksha Choudhary, Ashutosh Tiwari, Rashmi Madhuri, Prashant K. Sharma




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Editorial Board

Publication date: 30 August 2018
Source:Biosensors and Bioelectronics, Volume 114





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Enzyme-free homogeneous electrochemical biosensor for DNA assay using toehold-triggered strand displacement reaction coupled with host-guest recognition of Fe3O4@SiO2@β-CD nanocomposites

Publication date: 30 August 2018
Source:Biosensors and Bioelectronics, Volume 114
Author(s): Jingjing Jiang, Xinyi Lin, Dong Ding, Guowang Diao
Taking advantages of the toehold-triggered strand displacement reaction (TSDR) and host-guest interaction of β-cyclodextrin (β-CD), a facile enzyme-free and homogeneous electrochemical sensing strategy was designed for the sensitive assay of target DNA using Fe3O4@SiO2@β-CD nanocomposites and ferrocene-labeled hairpin DNA (H-1) as the capture and electrochemical probes, respectively. Upon addition of target molecule, the initiated TSDR process induced the conformational change of H-1, and subsequently stimulated the dynamic assembly of assist probes (A-1 and A-2) to generate H-1:A-1:A-2 duplex along with the release of target sequence. The released target could drive the next TSDR recycling and finally result in the formation of numerous DNA duplex. After the molecular recognition of Fe3O4@SiO2@β-CD nanocomposites, a large number of duplex were easily separated from the supernatant solution under an external magnetic field, which led to a decreased H-1 concentration in residual solution, concomitant with a remarkable reduction of peak current. Under the optimized conditions, wide linear range (1–5000 pM), low detection limit (0.3 pM), desirable reproducibility, good selectivity, and satisfactory practical analysis were obtained by the combination of the superior recognition capability of β-CD, TSDR-induced signal amplification, and homogeneous electroanalytical method. The proposed detection strategy could offer a universal approach for the monitoring of various biological analytes via the rational design of probe sequences.



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Predictors, utilization patterns, and overall survival of patients undergoing metastasectomy for metastatic renal cell carcinoma in the era of targeted therapy

Publication date: Available online 5 June 2018
Source:European Journal of Surgical Oncology
Author(s): Maxine Sun, Christian P. Meyer, Jose A. Karam, Guillermo de Velasco, Steven L. Chang, Sumanta K. Pal, Quoc-Dien Trinh, Toni K. Choueiri
IntroductionMetastasectomy (MSX) is considered a treatment option in patients with metastatic renal cell carcinoma (mRCC) at diagnosis, but its role in the targeted therapy era is unclear. We sought to describe the utilization trends of MSX and survival outcomes in a large US cohort.Materials and MethodsUsing the National Cancer Database, we identified patients undergoing MSX for mRCC at diagnosis between 2006-2013. Linear regression methods estimated utilization trends, and hierarchical models identified independent predictors of MSX after adjusting for hospital clustering. Kaplan-Meier survival estimates and Cox proportional hazard models were used to evaluate overall survival according to treatment after propensity-score matching.ResultsOf 6994 mRCC patients, 1976 underwent MSX (28.3%). Those treated at academic facilities were more likely to undergo a MSX (OR: 1.57, 95% CI 1.20-2.06, p=0.001). In contrast, older patients (OR: 0.99, 95% CI: 0.98-1.00), black race (OR: 0.65, 95% CI: 0.51-0.82), higher pT stage (OR: 0.76, 95% CI: 0.65-0.89), and who received targeted therapy (OR: 0.72, 95% CI: 0.63-0.82, all p≤0.008) were less likely to undergo MSX. Overall, MSX patients had an improved survival compared to non-MSX patients (HR: 0.83, 95% CI: 0.77-0.90, p<0.001), as well as among patients treated with targeted therapy (HR: 0.77, 95% CI: 0.77-0.96, p=0.008).ConclusionsOur findings indicate that MSX-treated patients may benefit from an improved overall survival compared to non-MSX treated patients. Good patient selection and a proper risk stratification strategy are still very important considerations.



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Relationship between complications and long-term prognosis after total gastrectomy with splenectomy for proximal advanced gastric cancer

Publication date: Available online 5 June 2018
Source:European Journal of Surgical Oncology
Author(s): Bing Quan, Wen-Tao Yan, Jiong-Jie Yu, Feng Shen, Tian Yang




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Water: From Pollution to Purification

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Polydrug use patterns, risk behavior and unmet healthcare need in a community-based sample of women who use cocaine, heroin or methamphetamine

Publication date: October 2018
Source:Addictive Behaviors, Volume 85
Author(s): Jennifer Lorvick, Erica N. Browne, Barrot H. Lambdin, Megan Comfort
BackgroundThe use of multiple illicit drugs (polydrug use) is associated with health-related harms and elevated risk of drug overdose. Polydrug use in common among women who use 'hard' drugs, such as cocaine, heroin or methamphetamine.MethodsQuantitative data collection was conducted with a community-recruited sample of 624 women who used heroin, methamphetamine or cocaine in Oakland, CA during 2014–2015. We conducted latent class analysis to classify polydrug use patterns. We assessed associations between classes of polydrug use and infectious disease risk behaviors, health care utilization and unmet health care need.ResultsWe identified four distinct classes of drug use: (1) predominantly crack (52% of women); (2) powder cocaine & non-heroin opioids (8%); (3) moderate polydrug use (25%); (4) heavy polydrug use (15%). Odds of sexual risk, injection drug use and unmet healthcare need were twice as high in the heavy polydrug use class as the predominantly crack class (p > 0.01 for each outcome). The rate of binge drinking (as days per month) was also significantly higher in the heavy polydrug class (p = 0.01). The moderate polydrug use class had higher odds of injection drug use and drug treatment participation, compared to the mainly crack class (p < 0.001 for each outcome). There were no differences between classes in health insurance or health care utilization.DiscussionReduction of polydrug use could be an effective harm reduction strategy to address sexual and injection risk among women. The use of both opioids and stimulants in three of the four classes suggests that multi-modal substance abuse treatment approaches may be most appropriate.



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Psychometric evaluation of the drinking refusal self-efficacy scale - revised with college students in the United States

Publication date: October 2018
Source:Addictive Behaviors, Volume 85
Author(s): Kray A. Scully, Richard S. Mohn, Michael B. Madson
Drinking refusal self-efficacy has recently emerged as a potential factor related to reduced alcohol consumption and alcohol-related negative consequences in college students. The Drinking Refusal Self-Efficacy Questionnaire-Revised (DRSEQ-R) has been commonly used to assess for drinking refusal self-efficacy. However, psychometric evaluation of the measure with college students from the United States is needed to enhance its research and clinical utility. The goal of the present study was to confirm the factor structure of the DRSEQ-R with a sample of traditional aged college students from the United States as well as assess the measurement invariance of the factor structure across sex and race and the measure's convergent validity with other common alcohol use measures. Traditional age college students (n = 1683, 73% women; 63% White, non-Hispanic) completed measures of drink refusal self-efficacy, protective behavioral strategies, weekly alcohol use, hazardous drinking, and alcohol-related negative consequences. Using exploratory factor analysis and multi-group confirmatory factor analyses, a three-factor structure was identified, but, unlike the DRSEQ-R, one item loaded onto the opportunistic relief factor instead of the social pressure factor. The proposed model registered more reliable internal consistencies across the subscales, was invariant across sex and race, and demonstrated acceptable convergent validity with other commonly used alcohol measures. The proposed model for the DRSE-R may be a more psychometrically sound way to assess for drinking refusal self-efficacy among college students in the United States. Implications, limitations, and future research directions are discussed.



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Visualizing Fatty Acid Flux

Publication date: 5 June 2018
Source:Cell Metabolism, Volume 27, Issue 6
Author(s): Ulf Eriksson, Annelie Falkevall
In a recent issue of Cell Metabolism, He et al. (2018) describes a novel technique to visualize cardiac intravascular lipoprotein lipase-mediated processing of triglyceride-rich lipoproteins and then follow the flux of released fatty acids across the endothelium to the underlying cardiomyocytes at high spatial resolution. This allows for detailed analyses of this clearly complex process.

Teaser

In a recent issue of Cell Metabolism, He et al. (2018) describes a novel technique to visualize cardiac intravascular lipoprotein lipase-mediated processing of triglyceride-rich lipoproteins and then follow the flux of released fatty acids across the endothelium to the underlying cardiomyocytes at high spatial resolution. This allows for detailed analyses of this clearly complex process.


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Obesity Protects Cancer from Drugs Targeting Blood Vessels

Publication date: 5 June 2018
Source:Cell Metabolism, Volume 27, Issue 6
Author(s): Yihai Cao
Drugs that target angiogenesis are commonly used for treating various cancers, but their clinical benefits are limited. In a recent Science Translational Medicine article, Incio et al. (2018) provide mechanistic insight on the role of obesity in the development of anti-VEGF drug resistance in human patients and murine models of breast cancer.

Teaser

Drugs that target angiogenesis are commonly used for treating various cancers, but their clinical benefits are limited. In a recent Science Translational Medicine article, Incio et al. (2018) provide mechanistic insight on the role of obesity in the development of anti-VEGF drug resistance in human patients and murine models of breast cancer.


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OXPHOS Defects Due to mtDNA Mutations: Glutamine to the Rescue!

Publication date: 5 June 2018
Source:Cell Metabolism, Volume 27, Issue 6
Author(s): Christos Chinopoulos
Mutations in mtDNA associated with OXPHOS defects preclude energy harnessing by OXPHOS. The work of Chen et al. (2018) is previewed, reporting flux pathways of glutamine catabolism in mtDNA mutant cells yielding high-energy phosphates through substrate-level phosphorylation and the influence exerted by the severity of OXPHOS impairment.

Teaser

Mutations in mtDNA associated with OXPHOS defects preclude energy harnessing by OXPHOS. The work of Chen et al. is previewed, reporting flux pathways of glutamine catabolism in mtDNA mutant cells yielding high-energy phosphates through substrate-level phosphorylation and the influence exerted by the severity of OXPHOS impairment.


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Of Mice Not Men? Actions of Interleukin-6 on Glucose Tolerance

Publication date: 5 June 2018
Source:Cell Metabolism, Volume 27, Issue 6
Author(s): Emma R. McGlone, Tricia M. Tan
In mice, interleukin-6 (IL-6) improves glucose tolerance via stimulation of glucagon-like peptide 1 (GLP-1) secretion. In this issue of Cell Metabolism, Lang Lehrskov et al. (2018) demonstrate that IL-6 infusion has GLP-1-dependent and -independent actions with opposing effects on glucose tolerance, resulting in an overall improvement in healthy male volunteers but no improvement in male patients with diabetes.

Teaser

In mice, interleukin-6 (IL-6) improves glucose tolerance via stimulation of glucagon-like peptide 1 (GLP-1) secretion. In this issue of Cell Metabolism, Lang Lehrskov et al. (2018) demonstrate that IL-6 infusion has GLP-1-dependent and -independent actions with opposing effects on glucose tolerance, resulting in an overall improvement in healthy male volunteers but no improvement in male patients with diabetes.


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Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States

Publication date: 5 June 2018
Source:Cell Metabolism, Volume 27, Issue 6
Author(s): Mark P. Mattson, Thiruma V. Arumugam
During aging, the cellular milieu of the brain exhibits tell-tale signs of compromised bioenergetics, impaired adaptive neuroplasticity and resilience, aberrant neuronal network activity, dysregulation of neuronal Ca²⁺ homeostasis, the accrual of oxidatively modified molecules and organelles, and inflammation. These alterations render the aging brain vulnerable to Alzheimer's and Parkinson's diseases and stroke. Emerging findings are revealing mechanisms by which sedentary overindulgent lifestyles accelerate brain aging, whereas lifestyles that include intermittent bioenergetic challenges (exercise, fasting, and intellectual challenges) foster healthy brain aging. Here we provide an overview of the cellular and molecular biology of brain aging, how those processes interface with disease-specific neurodegenerative pathways, and how metabolic states influence brain health.

Teaser

Mattson and Arumugam provide a comprehensive view of the cellular and molecular biology of brain aging and discuss how metabolic states influence brain health, including susceptibility to Alzheimer's and Parkinson's diseases and stroke. They consider how the sedentary lifestyle accelerates brain aging and discuss the potential for intermittent metabolic switching to counteract the process.


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Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota

Publication date: 5 June 2018
Source:Cell Metabolism, Volume 27, Issue 6
Author(s): Francesca Cignarella, Claudia Cantoni, Laura Ghezzi, Amber Salter, Yair Dorsett, Lei Chen, Daniel Phillips, George M. Weinstock, Luigi Fontana, Anne H. Cross, Yanjiao Zhou, Laura Piccio
Multiple sclerosis (MS) is more common in western countries with diet being a potential contributing factor. Here we show that intermittent fasting (IF) ameliorated clinical course and pathology of the MS model, experimental autoimmune encephalomyelitis (EAE). IF led to increased gut bacteria richness, enrichment of the Lactobacillaceae, Bacteroidaceae, and Prevotellaceae families and enhanced antioxidative microbial metabolic pathways. IF altered T cells in the gut with a reduction of IL-17 producing T cells and an increase in regulatory T cells. Fecal microbiome transplantation from mice on IF ameliorated EAE in immunized recipient mice on a normal diet, suggesting that IF effects are at least partially mediated by the gut flora. In a pilot clinical trial in MS patients, intermittent energy restriction altered blood adipokines and the gut flora resembling protective changes observed in mice. In conclusion, IF has potent immunomodulatory effects that are at least partially mediated by the gut microbiome.

Graphical abstract

Teaser

Intermittent fasting confers protection in the multiple sclerosis animal model through effects on the gut microbiota; similar changes to the gut microbiota were observed in relapsing multiple sclerosis patients undergoing intermittent energy restriction.


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Microglial Inflammatory Signaling Orchestrates the Hypothalamic Immune Response to Dietary Excess and Mediates Obesity Susceptibility

Publication date: 5 June 2018
Source:Cell Metabolism, Volume 27, Issue 6
Author(s): Martin Valdearcos, John D. Douglass, Megan M. Robblee, Mauricio D. Dorfman, Daniel R. Stifler, Mariko L. Bennett, Irene Gerritse, Rachael Fasnacht, Ben A. Barres, Joshua P. Thaler, Suneil K. Koliwad




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JAK/STAT3-Regulated Fatty Acid β-Oxidation Is Critical for Breast Cancer Stem Cell Self-Renewal and Chemoresistance

Publication date: 5 June 2018
Source:Cell Metabolism, Volume 27, Issue 6
Author(s): Tianyi Wang, Johannes Francois Fahrmann, Heehyoung Lee, Yi-Jia Li, Satyendra C. Tripathi, Chanyu Yue, Chunyan Zhang, Veronica Lifshitz, Jieun Song, Yuan Yuan, George Somlo, Rahul Jandial, David Ann, Samir Hanash, Richard Jove, Hua Yu




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12,13-diHOME: An Exercise-Induced Lipokine that Increases Skeletal Muscle Fatty Acid Uptake

Publication date: 5 June 2018
Source:Cell Metabolism, Volume 27, Issue 6
Author(s): Kristin I. Stanford, Matthew D. Lynes, Hirokazu Takahashi, Lisa A. Baer, Peter J. Arts, Francis J. May, Adam C. Lehnig, Roeland J.W. Middelbeek, Jeffrey J. Richard, Kawai So, Emily Y. Chen, Fei Gao, Niven R. Narain, Giovanna Distefano, Vikram K. Shettigar, Michael F. Hirshman, Mark T. Ziolo, Michael A. Kiebish, Yu-Hua Tseng, Paul M. Coen, Laurie J. Goodyear




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Protein Kinase C-β Dictates B Cell Fate by Regulating Mitochondrial Remodeling, Metabolic Reprogramming, and Heme Biosynthesis

Publication date: Available online 5 June 2018
Source:Immunity
Author(s): Carlson Tsui, Nuria Martinez-Martin, Mauro Gaya, Paula Maldonado, Miriam Llorian, Nathalie M. Legrave, Merja Rossi, James I. MacRae, Angus J. Cameron, Peter J. Parker, Michael Leitges, Andreas Bruckbauer, Facundo D. Batista
PKCβ-null (Prkcb^−/−) mice are severely immunodeficient. Here we show that mice whose B cells lack PKCβ failed to form germinal centers and plasma cells, which undermined affinity maturation and antibody production in response to immunization. Moreover, these mice failed to develop plasma cells in response to viral infection. At the cellular level, we have shown that Prkcb^−/− B cells exhibited defective antigen polarization and mTORC1 signaling. While altered antigen polarization impaired antigen presentation and likely restricted the potential of GC development, defective mTORC1 signaling impaired metabolic reprogramming, mitochondrial remodeling, and heme biosynthesis in these cells, which altogether overwhelmingly opposed plasma cell differentiation. Taken together, our study reveals mechanistic insights into the function of PKCβ as a key regulator of B cell polarity and metabolic reprogramming that instructs B cell fate.

Graphical abstract

Teaser

Lymphocyte activation is associated with major changes in metabolism. Tsui and colleagues demonstrate that PKCβ promotes metabolic reprogramming to drive effector fate decision in B cells.


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A Single-Cell Transcriptomic Atlas of Thymus Organogenesis Resolves Cell Types and Developmental Maturation

Publication date: Available online 5 June 2018
Source:Immunity
Author(s): Eric M. Kernfeld, Ryan M.J. Genga, Kashfia Neherin, Margaret E. Magaletta, Ping Xu, René Maehr
Thymus development is critical to the adaptive immune system, yet a comprehensive transcriptional framework capturing thymus organogenesis at single-cell resolution is still needed. We applied single-cell RNA sequencing (RNA-seq) to capture 8 days of thymus development, perturbations of T cell receptor rearrangement, and in vitro organ cultures, producing profiles of 24,279 cells. We resolved transcriptional heterogeneity of developing lymphocytes, and genetic perturbation confirmed T cell identity of conventional and non-conventional lymphocytes. We characterized maturation dynamics of thymic epithelial cells in vivo, classified cell maturation state in a thymic organ culture, and revealed the intrinsic capacity of thymic epithelium to preserve transcriptional regularity despite exposure to exogenous retinoic acid. Finally, by integrating the cell atlas with human genome-wide association study (GWAS) data and autoimmune-disease-related genes, we implicated embryonic thymus-resident cells as possible participants in autoimmune disease etiologies. This resource provides a single-cell transcriptional framework for biological discovery and molecular analysis of thymus organogenesis.

Graphical abstract

Teaser

Studies of thymus development typically lack single-cell resolution, use indirect readouts, or target narrow cell subsets. Using single-cell RNA sequencing during thymus organogenesis, Kernfeld and Genga et al. reveal cellular heterogeneity, interrogate developmental dynamics by direct observation, and pinpoint cell-specific expression patterns in stromal and blood populations.


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Naive B Cells with High-Avidity Germline-Encoded Antigen Receptors Produce Persistent IgM+ and Transient IgG+ Memory B Cells

Publication date: Available online 5 June 2018
Source:Immunity
Author(s): Kathryn A. Pape, Robert W. Maul, Thamotharampillai Dileepan, Amanda Schmidt Paustian, Patricia J. Gearhart, Marc K. Jenkins
Although immune memory often lasts for life, this is not the case for certain vaccines in some individuals. We sought a mechanism for this phenomenon by studying B cell responses to phycoerythrin (PE). PE immunization of mouse strains with Igh^b immunoglobulin (Ig) variable heavy chain (VH) genes elicited affinity-matured switched Ig memory B cells that declined with time, while the comparable population from an Igh^a strain was numerically stable. Igh^b strains had larger numbers of PE-specific naive B cells and generated smaller germinal center responses and larger numbers of IgM memory cells than the Igh^a strain. The properties of PE-specific B cells in Igh^b mice correlated with usage of a single VH that afforded high-affinity PE binding in its germline form. These results suggest that some individuals may be genetically predisposed to generate non-canonical memory B cell responses to certain antigens because of avid antigen binding via germline-encoded VH elements.

Graphical abstract

Teaser

Immunity induced by certain vaccines declines over time. By studying B cell responses to phycoerythrin, Pape et al. find that memory B cells can be short-lived when generated from precursors that experience unusually strong early signals through their un-mutated antigen receptors.


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Molecular targets of celastrol in cancer: Recent trends and advancements

Publication date: Available online 5 June 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Dharambir Kashyap, Ajay Sharma, Hardeep Singh Tuli, Katrin Sak, Tapan Mukherjee, Anupam Bishayee
Despite the advancement in the well-equipped and sophisticated laboratories and facilities, cancer remains to be a major cause of death worldwide. Consequently, further investigation of novel strategies need to be evolved. Since the last few decades, the utilization of phytochemicals is emerging against several human cancers, including lung, breast, colon carcinoma, lymphoma, and other hematological malignancies. Terpenoids are a category of therapeutically active phytochemicals that have been utilized against cancer, cardiovascular and neurodegenerative disorders. Particularly, celastrol, a pentacyclic terpenoid, is well-studied for its variety of pharmacological properties. It is well documented that celastrol can modulate a variety of signaling pathways. Celastrol's anti-proliferative role has been found to be associated with its pro-apoptotic (via protein kinase B), anti-angiogenic (via vascular endothelial growth factor and vascular endothelial growth factor receptor), anti-metastatic (via matrix metalloproteinases), and anti-inflammatory (via cytokines and chemokines) activities. This review describes various molecular mechanisms of celastrol for understanding the biology of cancer initiation, progression as well as designing efficacious therapeutic strategies.



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An investigation of some Schiff base derivatives as chemosensors for Zn(II): The performance characteristics and potential applications

Publication date: 5 October 2018
Source:Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Volume 203
Author(s): Ece Ergun, Ümit Ergun, Özgür İleri, Muhammed Fatih Küçükmüzevir
The fluorescence properties of four simple Schiff bases (LH2, LDMH2, LH2^H and LDM^HH2) and their potential application as chemosensors for the detection of zinc ion in aqueous solution have been investigated. While LH2 and LDMH2 have displayed specific recognition to Zn(II), the reduced derivatives (LH2^H and LDM^HH2) of these ligands have shown no fluorescence response due to the lack of CN group. The Job plots, fluorescence titration experiments and ESI-MS results indicate the formation of 1:1 complexes between sensors and Zn(II). The analytic methods based on LH2 and LDMH2 as chemosensors have been proposed and optimized to detect Zn(II) ions in aqueous solution. The optimized methods have shown a good range of linearity, high precision, good accuracy and low detection limit. As an alternative to these methods, LH2 and LDMH2 have the capability to detect Zn(II) ions by naked eye under UV lamp. Moreover, LH2-Zn and LDMH2-Zn complexes have the ability to be a staining agent for identifying the radiation treatment of food by DNA comet assay.

Graphical abstract

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Structural diversity and luminescent sensing of three coordination polymers based on the hydrolysates of N,N′-bis(3,5-dicarboxylatophenyl)pyromelliticdi-imide)

Publication date: 5 November 2018
Source:Journal of Molecular Structure, Volume 1171
Author(s): Liming Fan, Jiang Wang, Li Zhao, Yujuan Zhang, Xiaoqing Wang, Tuoping Hu, Xiutang Zhang
Based on the hydrolysates of N,N′-bis(3,5-dicarboxylatophenyl)pyromelliticdi-imide) (H4L) and 1,3-bis(imidazol-1-ylmethyl)benzene (bimb), three coordination polymers, namely, {[Zn(BTC)0.5(bimb)]·4H2O}n (1), [Cu(BTC)0.5(bimb)]n (2), and {[Cd(AIP)(H2O)]·H2O}n (3), have been obtained under solvothermal conditions. The possible hydrolysis mechanism of H4L was investigated here. Structural analyses reveal that complex 1 is a 3D (4,4)-c {6⁴.8²}{6⁶}2-bbf net. Complex 2 displays a 2D 4-c {3².6².7²}-kgm sheet. While complex 3 exhibits a 3D (3,6)-c {4.6²}2{4².6¹⁰.8³}-rtl net based on binuclear {Cd2(COO)4} SBUs. Besides, luminescent sensing investigation indicated that 1 and 3 exhibit highly sensitive and selective sensing of chromate anions in aqueous solution.

Graphical abstract

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Characterization of polymer-coated CdSe/ZnS quantum dots and investigation of their behaviour in soil solution at relevant concentration by asymmetric flow field-flow fractionation – multi angle light scattering – inductively coupled plasma - mass spectrometry

Publication date: 22 October 2018
Source:Analytica Chimica Acta, Volume 1028
Author(s): Stéphane Faucher, Gaëlle Charron, Elias Lützen, Philippe Le Coustumer, Dirk Schaumlöffel, Yann Sivry, Gaëtane Lespes
A careful separation, identification and characterization of polymer-coated quantum dots (P-QDs) in complex media such as soil solution is the key point to understand their behaviour and to accurately predict their fate in the environment. In the present study, a synthesized CdSe/ZnS core/shell P-QDs suspension, proved to be stable for at least six months, was investigated with respect to P-QDs dimension, structure and elemental composition. Separation of P-QDs and size distribution determination were carried out by Asymmetric Flow Field-Flow Fractionation (AF4) - Multi Angle Light Scattering (MALS). AF4 and MALS were coupled to Inductively Coupled Plasma-Mass Spectrometry (ICPMS) as a selective and sensitive technique for the detection and the characterization of metallic and metalloid analytes. The exploration of element-specific data obtained by ICPMS after AF4 separation enabled the signal to be deconvoluted reliably. Thus, 3 classes of size populations were identified from the whole population of P-QDs. Additionally, a soil solution and a mix of P-QDs suspension with soil solution were characterized by the same method. This strategy enabled the P-QD population, which interacted with the soil solution, to be determined, this interaction leading either to an aggregation or dissolution of the P-QDs. Reproducibility and recovery of the size distributions and element concentrations were examined for each sample. Complementarily, Dynamic Light Scattering (DLS) and Scanning Transmission Electron Microscopy (STEM) were used jointly with AF4-MALS-ICPMS in order to demonstrate all potentialities of this coupling technique.

Graphical abstract

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Family-based treatment for transition age youth: parental self-efficacy and caregiver accommodation

Abstract

Background

Family-Based Treatment (FBT) is the first line of care in paediatric treatment while adult programs focus on individualized models of care. Transition age youth (TAY) with Anorexia Nervosa (AN) are in a unique life stage and between systems of care. As such, they and their caregivers may benefit from specialized, developmentally tailored models of treatment.

Methods

The primary purpose of this study was to assess if parental self-efficacy and caregiver accommodation changed in caregivers during the course of FBT-TAY for AN. The secondary aim was to determine if changes in parental self-efficacy and caregiver accommodation contributed to improvements in eating disorder behaviour and weight restoration in the transition age youth with AN. Twenty-six participants (ages 16–22) and 39 caregivers were recruited. Caregivers completed the Parents versus Anorexia Scale and Accommodation and Enabling Scale for Eating Disorders at baseline, end-of-treatment (EOT), and 3 months follow-up.

Results

Unbalanced repeated measures designs for parental self-efficacy and caregiver accommodation towards illness behaviours were conducted using generalized estimation equations. Parental self-efficacy increased from baseline to EOT, although not significantly (p = .398). Parental self-efficacy significantly increased from baseline to 3 months post-treatment (p = .002). Caregiver accommodation towards the illness significantly decreased from baseline to EOT (p = 0.0001), but not from baseline to 3 months post-treatment (p = 1.000). Stepwise ordinary least squares regression estimates of eating disorder behaviour and weight restoration did not show that changes in parental-self efficacy and caregiver accommodation predict eating disorder behaviour or weight restoration at EOT or 3 months post-treatment.

Conclusions

Our findings demonstrate, albeit preliminary at this stage, that FBT-TAY promotes positive increases in parental self-efficacy and assists caregivers in decreasing their accommodation to illness behaviours for transition age youth with AN. However, changes in the parental factors did not influence changes in eating and weight in the transition age youth.

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3D heterogeneous islet organoid generation from human embryonic stem cells using a novel engineered hydrogel platform

Publication date: September 2018
Source:Biomaterials, Volume 177
Author(s): Joseph Candiello, Taraka Sai Pavan Grandhi, Saik Kia Goh, Vimal Vaidya, Maya Lemmon-Kishi, Kiarash Rahmani Eliato, Robert Ros, Prashant N. Kumta, Kaushal Rege, Ipsita Banerjee
Organoids, which exhibit spontaneous organ specific organization, function, and multi-cellular complexity, are in essence the in vitro reproduction of specific in vivo organ systems. Recent work has demonstrated human pluripotent stem cells (hPSCs) as a viable regenerative cell source for tissue-specific organoid engineering. This is especially relevant for engineering islet organoids, due to the recent advances in generating functional beta-like cells from human pluripotent stem cells. In this study, we report specific engineering of regenerative islet organoids of precise size and cellular heterogeneity, using a novel hydrogel system, Amikagel. Amikagel facilitated controlled and spontaneous aggregation of human embryonic stem cell derived pancreatic progenitor cells (hESC-PP) into robust homogeneous spheroids. This platform further allowed fine control over the integration of multiple cell populations to produce heterogeneous spheroids, which is a necessity for complex organoid engineering. Amikagel induced hESC-PP spheroid formation enhanced pancreatic islet-specific Pdx-1 and NKX6.1 gene and protein expression, while also increasing the percentage of committed population. hESC-PP spheroids were further induced towards mature beta-like cells which demonstrated increased Beta-cell specific INS1 gene and C-peptide protein expression along with functional insulin production in response to in vitro glucose challenge. Further integration of hESC-PP with biologically relevant supporting endothelial cells resulted in multicellular organoids which demonstrated spontaneous maturation towards islet-specific INS1 gene and C-peptide protein expression along with a significantly developed extracellular matrix support system. These findings establish Amikagel –facilitated platform ideal for islet organoid engineering.



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Novel theranostic nanoplatform for complete mice tumor elimination via MR imaging-guided acid-enhanced photothermo-/chemo-therapy

Publication date: September 2018
Source:Biomaterials, Volume 177
Author(s): Bei Li, Jie Tang, Weiyu Chen, Guanyu Hao, Nyoman Kurniawan, Zi Gu, Zhi Ping Xu
Non-invasive imaging-guided tumor therapy requires new-generation bio-nanomaterials to sensitively respond to the unique tumor microenvironment for precise diagnosis and efficient treatment. Here, we report such a theranostic nanoplatform by engineering defect-rich multifunctional Cu-doped layered double hydroxide (Cu-LDH) nanoparticles, which integrates pH-sensitive T1-magnetic resonance imaging (MRI), acid-enhanced photothermal therapy and heat-facilitated chemotherapy. As characterized with EXAFS and XPS, smaller Cu-LDH nanoparticles possess a considerable amount of defects around Cu cations, an advantageous microstructure that enables a high photothermal conversion of 808 nm NIR laser (53.1%). The exposure of CuOH octahedra on the LDH surface makes the photothermal conversion significantly acid-enhanced (53.1% at pH 7.0 vs. 81.9% at pH 5.0). This Cu peculiar microstructure also makes T1-MRI very pH-sensitive, a desirable guide for subsequent tumor photothermal therapy. Combined photothermal therapy and chemotherapy lead to nearly complete elimination of tumor tissues in vivo with a low injection dose of agents. Therefore, this novel defect-rich Cu-LDH nanoplatform is one of promising tumor-specific nanotheranostic agents for non-invasive imaging-guided combinational therapy.

Graphical abstract

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Transfection of gene regulation nanoparticles complexed with pDNA and shRNA controls multilineage differentiation of hMSCs

Publication date: September 2018
Source:Biomaterials, Volume 177
Author(s): Hye Jin Kim, Se Won Yi, Hyun Jyung Oh, Jung Sun Lee, Ji Sun Park, Keun-Hong Park
Overexpression and knockdown of specific proteins can control stem cell differentiation for therapeutic purposes. In this study, we fabricated RUNX2, SOX9, and C/EBPα plasmid DNAs (pDNAs) and ATF4-targeting shRNA (shATF4) to induce osteogenesis, chondrogenesis, and adipogenesis of human mesenchymal stem cells (hMSCs). The pDNAs and shATF4 were complexed with TRITC-gene regulation nanoparticles (GRN). Osteogenesis-related gene expression was reduced at early (12 h) and late (36 h) time points after co-delivery of shATF4 and SOX9 or C/EBPα pDNA, respectively, and osteogenesis was inhibited in these hMSCs. By contrast, osteogenesis-related genes were highly expressed upon co-delivery of RUNX2 and ATF4 pDNAs. DEX in GRN enhanced chondrogenic differentiation. Expression of osteogenesis-, chondrogenesis-, and adipogenesis-related genes was higher in hMSCs transfected with NPs complexed with RUNX2 and ATF4 pDNAs, shATF4 and SOX9 pDNA, and shATF4 and C/EBPα pDNA for 72 h than in control hMSCs, respectively. Moreover, delivery of these NPs also increased expression of osteogenesis-, chondrogenesis-, and adipogenesis-related proteins. These alterations in expression led to morphological changes, indicating that hMSCs differentiated into osteoblasts, chondrocytes, and adipose cells.



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Nanodiamonds as “artificial proteins”: Regulation of a cell signalling system using low nanomolar solutions of inorganic nanocrystals

Publication date: September 2018
Source:Biomaterials, Volume 176
Author(s): Lukas Balek, Marcela Buchtova, Michaela Kunova Bosakova, Miroslav Varecha, Silvie Foldynova-Trantirkova, Iva Gudernova, Iva Vesela, Jan Havlik, Jitka Neburkova, Stuart Turner, Mateusz Adam Krzyscik, Malgorzata Zakrzewska, Lars Klimaschewski, Peter Claus, Lukas Trantirek, Petr Cigler, Pavel Krejci
The blocking of specific protein-protein interactions using nanoparticles is an emerging alternative to small molecule-based therapeutic interventions. However, the nanoparticles designed as "artificial proteins" generally require modification of their surface with (bio)organic molecules and/or polymers to ensure their selectivity and specificity of action. Here, we show that nanosized diamond crystals (nanodiamonds, NDs) without any synthetically installed (bio)organic interface enable the specific and efficient targeting of the family of extracellular signalling molecules known as fibroblast growth factors (FGFs). We found that low nanomolar solutions of detonation NDs with positive ζ-potential strongly associate with multiple FGF ligands present at sub-nanomolar concentrations and effectively neutralize the effects of FGF signalling in cells without interfering with other growth factor systems and serum proteins unrelated to FGFs. We identified an evolutionarily conserved FGF recognition motif, ∼17 amino acids long, that contributes to the selectivity of the ND-FGF interaction. In addition, we inserted this motif into a de novo constructed chimeric protein, which significantly improved its interaction with NDs. We demonstrated that the interaction of NDs, as purely inorganic nanoparticles, with proteins can mitigate pathological FGF signalling and promote the restoration of cartilage growth in a mouse limb explant model. Based on our observations, we foresee that NDs may potentially be applied as nanotherapeutics to neutralize disease-related activities of FGFs in vivo.



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A “top-down” approach to actuate poly(amine-co-ester) terpolymers for potent and safe mRNA delivery

Publication date: September 2018
Source:Biomaterials, Volume 176
Author(s): Yuhang Jiang, Alice Gaudin, Junwei Zhang, Tushar Agarwal, Eric Song, Amy C. Kauffman, Gregory T. Tietjen, Yongheng Wang, Zhaozhong Jiang, Christopher J. Cheng, W. Mark Saltzman
Gene delivery is known to be a complicated multi-step biological process. It has been observed that subtle differences in the structure and properties of polymeric materials used for gene delivery can lead to dramatic differences in transfection efficiency. Therefore, screening of properties is pivotal to optimizing the polymer. So far, most polymeric materials are built in a "bottom-up" manner, i.e. synthesized from monomers that allow modification of polymer composition or structural factors. With this method, we previously synthesized and screened a library of biodegradable poly(amine-co-ester) (PACE) terpolymers for optimized DNA delivery. However, it can be tedious and time consuming to synthesize a polymer library for screening, particularly when small changes of a factor need to be tested, when multiple factors are involved, and when the effects of different factors are synergistic. In the present work, we evaluate the potential of PACE to deliver mRNA. After observing that mRNA transfection efficiency was highly dependent on both end group composition and molecular weight (MW) of PACE in a synergistic manner, we developed a "top-down" process we called actuation, to simultaneously vary these two factors. Some of the actuated PACE (aPACE) materials presented superior mRNA delivery properties compared to regular PACE, with up to a 10⁶-fold-increase in mRNA transfection efficiency in vitro. Moreover, when aPACE was used to deliver mRNA coding for erythropoietin (EPO) in vivo, it produced high levels of EPO in the blood for up to 48 h without inducing systemic toxicity. This polymer constitutes a new delivery vehicle for mRNA-based treatments that provides safe yet potent protein production.

Graphical abstract

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Molecular targets of celastrol in cancer: Recent trends and advancements

Publication date: Available online 5 June 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Dharambir Kashyap, Ajay Sharma, Hardeep Singh Tuli, Katrin Sak, Tapan Mukherjee, Anupam Bishayee
Despite the advancement in the well-equipped and sophisticated laboratories and facilities, cancer remains to be a major cause of death worldwide. Consequently, further investigation of novel strategies need to be evolved. Since the last few decades, the utilization of phytochemicals is emerging against several human cancers, including lung, breast, colon carcinoma, lymphoma, and other hematological malignancies. Terpenoids are a category of therapeutically active phytochemicals that have been utilized against cancer, cardiovascular and neurodegenerative disorders. Particularly, celastrol, a pentacyclic terpenoid, is well-studied for its variety of pharmacological properties. It is well documented that celastrol can modulate a variety of signaling pathways. Celastrol's anti-proliferative role has been found to be associated with its pro-apoptotic (via protein kinase B), anti-angiogenic (via vascular endothelial growth factor and vascular endothelial growth factor receptor), anti-metastatic (via matrix metalloproteinases), and anti-inflammatory (via cytokines and chemokines) activities. This review describes various molecular mechanisms of celastrol for understanding the biology of cancer initiation, progression as well as designing efficacious therapeutic strategies.



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Contents Continued

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68





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Motor coordination and synaptic plasticity deficits are associated with increased cerebellar activity of NADPH oxidase, CAMKII, and PKC at preplaque stage in the TgCRND8 mouse model of Alzheimer's disease

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68
Author(s): Roberto Russo, Fabio Cattaneo, Pellegrino Lippiello, Claudia Cristiano, Fabio Zurlo, Martina Castaldo, Carlo Irace, Tiziana Borsello, Rita Santamaria, Rosario Ammendola, Antonio Calignano, Maria Concetta Miniaci
Numerous studies indicate that the cerebellum undergoes structural and functional neurodegenerative changes in Alzheimer's disease. The purpose of this study was to examine the extent of cerebellar alterations at early, preplaque stage of the pathology in TgCRND8 mice through behavioral, electrophysiological, and molecular analysis. Balance beam test and foot-printing analysis revealed significant motor coordination and balance deficits in 2-month-old TgCRND8 mice compared to their littermates. Patch-clamp recordings performed on cerebellar slices of transgenic mice showed synaptic plasticity deficit and loss of noradrenergic modulation at parallel fiber-Purkinje cell synapse suggesting an early dysfunction of the cerebellar circuitry due to amyloid precursor protein overexpression. Finally, western blot analysis revealed an enhanced expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p47^phox and p67^phox as well as Ca²⁺/calmodulin-dependent protein kinase and protein kinase C alpha in the cerebellum of 2-month-old transgenic mice. Therefore, we propose the existence of self-sustaining feedback loop involving the formyl peptide receptor 2-reactive oxygen species-Ca²⁺/calmodulin-dependent protein kinase II-protein kinase C alpha pathway that may promote reactive oxygen species generation in the early stage of Alzheimer's disease and eventually contribute to the exacerbation of pathological phenotype.



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A rare variant in MLKL confers susceptibility to ApoE ɛ4-negative Alzheimer's disease in Hong Kong Chinese population

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68
Author(s): Binbin Wang, Suying Bao, Zhigang Zhang, Xueya Zhou, Jing Wang, Yanhui Fan, Yan Zhang, Yan Li, Luhua Chen, Yizhen Jia, Jiang Li, Miaoxin Li, Wenhua Zheng, Nan Mu, Liqiu Wang, Zhe Yu, Dana S.M. Wong, Yalun Zhang, Joseph Kwan, Henry Ka-Fung Mak, Amirthagowri Ambalavanan, Sirui Zhou, Wangwei Cai, Jin Zheng, Shishu Huang, Guy A. Rouleau, Wanling Yang, Ekaterina Rogaeva, Xu Ma, Peter St George-Hyslop, Leung Wing Chu, You-Qiang Song
Alzheimer's disease (AD) is the most common neurodegenerative disorders in the elderly. To identify rare genetic factors other than apolipoprotein E ɛ4 allele (ApoE ɛ4) contributing to the pathogenesis of late-onset AD (LOAD), we conducted a whole-exome analysis of 246 ApoE ɛ4-negative LOAD cases and 172 matched controls in Hong Kong Chinese population. LOAD patients showed a significantly higher burden of rare loss-of-function variants in genes related to immune function than healthy controls. Among the genes involved in immune function, we identified a rare stop-gain variant (p.Q48X) in mixed lineage kinase domain like pseudokinase (MLKL) gene present exclusively in 6 LOAD cases. MLKL is expressed in neurons, and the its expression levels in the p.Q48X carriers were significantly lower than that in age-matched wild-type controls. The ratio of Aβ42 to Aβ40 significantly increased in MLKL knockdown cells compared to scramble controls. MLKL loss-of-function mutation might contribute to late-onset ApoE ɛ4-negative AD in the Hong Kong Chinese population.



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Education amplifies brain atrophy effect on cognitive decline: implications for cognitive reserve

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68
Author(s): Dan Mungas, Brandon Gavett, Evan Fletcher, Sarah Tomaszewski Farias, Charles DeCarli, Bruce Reed
Level of education is often regarded as a proxy for cognitive reserve in older adults. This implies that brain degeneration has a smaller effect on cognitive decline in those with more education, but this has not been directly tested in previous research. We examined how education, quantitative magnetic resonance imaging–based measurement of brain degeneration, and their interaction affect cognitive decline in diverse older adults spanning the spectrum from normal cognition to dementia. Gray matter atrophy was strongly related to cognitive decline. While education was not related to cognitive decline, brain atrophy had a stronger effect on cognitive decline in those with more education. Importantly, high education was associated with slower decline in individuals with lesser atrophy but with faster decline in those with greater atrophy. This moderation effect was observed in Hispanics (who had high heterogeneity of education) but not in African-Americans or Caucasians. These results suggest that education is an indicator of cognitive reserve in individuals with low levels of brain degeneration, but the protective effect of higher education is rapidly depleted as brain degeneration progresses.



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Study of GCH1 and TH genes in Chinese patients with Parkinson's disease

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68
Author(s): Ya-Ping Yan, Bo Zhang, Ting Shen, Xiao-Li Si, Zhang-Yu Guo, Jun Tian, Cong-Ying Xu, Bao-Rong Zhang
Whole-exome sequencing of Parkinson's disease (PD) patients has revealed that the frequency of GTP-cyclohydrolase I (GCH1) variants was significantly higher in patients than in controls. GCH1 rs11158026 was also found to increase the risk of PD. To investigate genetic contribution of dopa-responsive dystonia–related genes to PD, GCH1, and tyrosine hydroxylase (TH) were tested in PD patients. A total of 859 study subjects comprising 421 patients with PD and 438 controls were recruited. For GCH1 gene, one known variant (c.239G > A, p.S80N) was detected in a patient who was diagnosed with PD clinically. In TH, 3 heterozygous variants, c.1495G > A (p. V499M, rs1800033), c.334 A > G (p.V112M, rs6356), and c.813 G > A (p. K271K, rs6357), were identified. After stratification by age, the frequency of rs6356G allele was significantly lower (p = 0.041) for the late-onset PD group than controls. Our results indicate that to analyze the relationship between dopa-responsive dystonia–related genes and PD, it is important to screen GCH1 and test rs6356 of TH in a larger sample.



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Targeted exome sequencing reveals homozygous TREM2 R47C mutation presenting with behavioral variant frontotemporal dementia without bone involvement

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68
Author(s): Adeline S.L. Ng, Yi Jayne Tan, Zhao Yi, Moses Tandiono, Elaine Chew, Jacqueline Dominguez, Mabel Macas, Ebonne Ng, Shahul Hameed, Simon Ting, Eng King Tan, Jia Nee Foo, Nagaendran Kandiah
To identify genes associated with frontotemporal dementia (FTD) in South-East Asia, targeted exome sequencing and C9orf72 genotyping was performed in 198 subjects (52 patients with FTD and 146 healthy controls) who were screened for mutations in 12 FTD-associated genes. We detected a homozygous TREM2 R47C mutation in a patient with behavioral variant FTD without bone cysts or bone-associated phenotype. Two novel nonsense GRN mutations in 3 FTD patients from the Philippines were detected, but no known pathogenic mutations in other FTD-associated genes were found. In 45 subjects screened for C9orf72 repeat expansions, no pathogenic expansion (≥30 repeats) was identified, but there was a higher proportion of intermediate length (≥10–29 repeats) alleles in patients compared with controls (8/90 alleles, 8.9% vs. 9/164 alleles, 5.5%). Overall, we detected a mutation rate of 7.7% (4/52 patients) in our cohort. Given recent findings of enrichment of rare TREM2 variants (including R47C) in Alzheimer's disease, it is notable that we detected a homozygous TREM2 R47C carrier presenting with an FTD rather than an Alzheimer's disease phenotype.



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Longitudinal accrual of neocortical amyloid burden is associated with microstructural changes of the fornix in cognitively normal adults

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68
Author(s): Zhuang Song, Michelle E. Farrell, Xi Chen, Denise C. Park
The fornix and parahippocampal cingulum are 2 major limbic tracts in the core memory network of the hippocampus. Although these fiber tracts are known to degrade with Alzheimer's disease (AD), little is known about their vulnerability in the asymptomatic phase of AD. In this longitudinal study of cognitively normal adults, we assessed amyloid-beta (Aβ) plaques using positron emission tomography and white matter microstructure using diffusion tensor imaging. We found that an increase of neocortical Aβ burden over time was associated with an increase of radial diffusivity in the fornix but not in the parahippocampal cingulum. The effect of increasing neocortical Aβ burden on the fornix remained significant after controlling for baseline measures, head motion, global brain atrophy, regional Aβ burden in the hippocampus, or microstructural changes in the global white matter. In addition, microstructural changes in the fornix were not associated with decline of episodic memory or other cognitive abilities. Our findings suggest that microstructural changes in the fornix may be an early sign in the asymptomatic phase of AD.



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Cover 2: Editorial Advisory Board

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68





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Upregulation of histone deacetylase 2 in laser capture nigral microglia in Parkinson's disease

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68
Author(s): Yuyan Tan, Elaine Delvaux, Jennifer Nolz, Paul D. Coleman, Shengdi Chen, Diego Mastroeni
Histone deacetylase (HDAC) inhibitors have been widely reported to have considerable therapeutic potential in a host of neurodegenerative diseases. However, HDAC inhibitor selectivity and specificity in specific cell classes have been a source of much debate. To address the role of HDAC2 in specific cell classes, and in disease, we examined glial protein and mRNA levels in the substantia nigra (SN) of Parkinson's disease (PD) and normal controls (NCs) by immunohistochemistry and laser captured microdissection followed by quantitative real time polymerase chain reaction. Differential expression analysis in immunohistochemically defined laser capture microglia revealed significant upregulation of HDAC2 in the PD SN compared to NC subjects. Complementary in vivo evidence reveals significant upregulation of HDAC2 protein levels in PD SN microglia compared to NC subjects. Correspondingly, human immortalized telencephalic/mesencephalic microglial cells reveal significant upregulation of HDAC2 in the presence of the potent microglial activator lipopolysaccharide. These data provide evidence that selective inhibition of HDAC2 in PD SN microglia could be a promising approach to treat microglial-initiated nigral dopaminergic neuronal cell loss in PD.



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Classifying Alzheimer's disease with brain imaging and genetic data using a neural network framework

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68
Author(s): Kaida Ning, Bo Chen, Fengzhu Sun, Zachary Hobel, Lu Zhao, Will Matloff, Arthur W. Toga
A long-standing question is how to best use brain morphometric and genetic data to distinguish Alzheimer's disease (AD) patients from cognitively normal (CN) subjects and to predict those who will progress from mild cognitive impairment (MCI) to AD. Here, we use a neural network (NN) framework on both magnetic resonance imaging-derived quantitative structural brain measures and genetic data to address this question. We tested the effectiveness of NN models in classifying and predicting AD. We further performed a novel analysis of the NN model to gain insight into the most predictive imaging and genetics features and to identify possible interactions between features that affect AD risk. Data were obtained from the AD Neuroimaging Initiative cohort and included baseline structural MRI data and single nucleotide polymorphism (SNP) data for 138 AD patients, 225 CN subjects, and 358 MCI patients. We found that NN models with both brain and SNP features as predictors perform significantly better than models with either alone in classifying AD and CN subjects, with an area under the receiver operating characteristic curve (AUC) of 0.992, and in predicting the progression from MCI to AD (AUC=0.835). The most important predictors in the NN model were the left middle temporal gyrus volume, the left hippocampus volume, the right entorhinal cortex volume, and the APOE (a gene that encodes apolipoprotein E) ɛ4 risk allele. Furthermore, we identified interactions between the right parahippocampal gyrus and the right lateral occipital gyrus, the right banks of the superior temporal sulcus and the left posterior cingulate, and SNP rs10838725 and the left lateral occipital gyrus. Our work shows the ability of NN models to not only classify and predict AD occurrence but also to identify important AD risk factors and interactions among them.



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DNAJC12 mutation is rare in Chinese Han population with Parkinson's disease

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68
Author(s): Yu Fan, Zhi-hua Yang, Fang Li, Xin-chao Hu, Yi-wei Yue, Jing Yang, Yu-tao Liu, Han Liu, Yan-lin Wang, Chang-he Shi, Yu-ming Xu
Recently, mutations of DNAJC12 gene were reported to be associated with early-onset parkinsonism, progressive neurodevelopmental delay, and dystonia in several unrelated pedigrees. This study aimed to evaluate DNAJC12 coding mutations in sporadic Chinese Han patients with Parkinson's disease (PD) and test whether an age-of-onset effect exists. Seven hundred two Chinese Han sporadic PD patients, including 181 early-onset PD and 521 late-onset PD, and 728 healthy controls were recruited. No documented disease-causing mutation of DNAJC12 was identified, but we found 7 single-nucleotide polymorphisms. Allele frequencies did not differ between all the PD patients and controls or between any 2 subgroups for all these single-nucleotide polymorphisms. Our study suggests that DNAJC12 mutation is not a risk factor of PD in Chinese Han population, and no age-of-onset effect was verified.



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Association analyses of variants of SIPA1L2, MIR4697, GCH1, VPS13C, and DDRGK1 with Parkinson's disease in East Asians

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68
Author(s): Ming Zou, Rui Li, Jian-Yong Wang, Ke Wang, Ya-Nan Wang, Yang Li, Fei-Xue Ji, Sheng-Nan Sun, Shi-Shi Huang, Hui-Hui Fan, Chen-Ping Huang, Xiong Zhang, Jian-Hong Zhu
A recent large-scale European-originated genome-wide association data meta-analysis followed by a replication study identified 6 new risk loci for Parkinson's disease (PD), which include rs10797576/SIPA1L2, rs117896735/INPP5F, rs329648/MIR4697, rs11158026/GCH1, rs2414739/VPS13C, and rs8118008/DDRGK1. However, whether these new loci are associated with PD in Asian populations remain elusive. The INPP5F is nonpolymorphic in Asians. The present study aimed to understand the effects of the other 5 new loci in a Han Chinese population comprising 579 sporadic PD patients and 642 controls. Significant associations with PD were observed in the variants of SIPA1L2 (p = 0.001) and VPS13C (p = 0.007), where the T (odd ratio [OR] = 1.484, 95% confidence interval [CI] 1.186–1.858) and A (OR = 1.362, 95% CI 1.087–1.707) alleles serve as the risk alleles, respectively. The genotype distributions in the SIPA1L2 and VPS13C variants were also different between the patients and controls (p = 0.002 and p = 0.023, respectively). In contrast, no significant association with PD was found in the variants of MIR4697, GCH1, and DDRGK1 either in allele or genotype frequencies. Noteworthy, a followed meta-analysis of East Asian studies suggested an association of the GCH1 variant with PD (p = 0.04, OR 1.08, 95% CI 1.00–1.16), while the other results are in line with those of our cohort. In conclusion, our study together with meta-analyses demonstrates that the variants of SIPA1L2 and VPS13C, potentially GCH1, but not of MIR4697 and DDRGK1, are associated with PD susceptibility in East Asians.



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Genome-wide association identifies a novel locus for delirium risk

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68
Author(s): Thomas H. McCoy, Kamber Hart, Amelia Pellegrini, Roy H. Perlis
We aimed to identify common genetic variations associated with delirium through genome-wide association testing in a hospital biobank. We applied a published electronic health record-based definition of delirium to identify cases of delirium, and control individuals with no history of delirium, from a biobank spanning 2 Boston academic medical centers. Among 6035 individuals of northern European ancestry, including 421 with a history of delirium, we used logistic regression to examine genome-wide association. We identified one locus spanning multiple genes, including 3 interleukin-related genes, associated with p = 1.41e-8, and 5 other independent loci with p < 5e-7. Our results do not support previously reported candidate gene associations in delirium. Identifying common-variant associations with delirium may provide insight into the mechanisms responsible for this complex and multifactorial outcome. Using standardized claims-based phenotypes in biobanks should allow the larger scale investigations required to confirm novel loci such as the one we identify.



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Mutation screening of the TIA1 gene in Chinese patients with amyotrophic lateral sclerosis/frontotemporal dementia

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68
Author(s): XiaoJing Gu, YongPing Chen, QianQian Wei, Bei Cao, RuWei Ou, XiaoQin Yuan, YanBin Hou, LingYu Zhang, Hui Liu, XuePing Chen, Hui-Fang Shang
Mutations in the low-complexity domain (LCD) of T-cell intracellular antigen-1 (TIA1) have been reported to be associated with amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) in the Caucasian population. In the present study, we aimed to screen mutations in the LCD (exon 11–13) of TIA1 and determine the mutation frequency in Chinese ALS/FTD patients. A total of 740 ALS patients, including 721 sporadic ALS (sALS), 19 familial ALS, 24 FTD patients, and 501 healthy controls, were directly sequenced. A novel variant p.S349P was found in a male sALS patient who presented with mild cognitive decline and a survival time of 1.23 years since onset. No mutation in the LCD of TIA1 was found in the familial ALS and FTD patients. The mutation frequency of TIA1 was 0.14% (1/721) in Chinese sALS patients, which suggests that TIA1 mutation is an uncommon genetic cause for ALS in the Chinese population.



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Cover 4: Contents

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68





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Scholar : Molecular Medicine Reports - Volume:18 Number:1

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TABLE OF CONTENTS July-2018 Volume 18 Issue 1

Vitamin K‑dependent proteins involved in bone and cardiovascular health (Review) Lianpu Wen, Jiepeng Chen, Lili Duan, Shuzhuang Li View Abstract ❯
Long noncoding RNA KCNQ1OT1 promotes proliferation and epithelial‑mesenchymal transition by regulation of SMAD4 expression in lens epithelial cells Bin Chen, Jian Ma, Chunwei Li, Yong Wang View Abstract ❯
Effect of combined chondroitinase ABC and hyperbaric oxygen therapy in a rat model of spinal cord injury Xiaoyang Liu, Jiefeng Wang, Guangkuo Li, Honglin Lv View Abstract ❯
Effects of osteoprotegerin/TNFRSF11B in two models of abdominal aortic aneurysms Emina Vorkapic, Anne Kunath, Dick Wågsäter View Abstract ❯
Serum proteomic analysis of the anti‑arthritic effects of sinomenine on rats with collagen‑induced arthritis Xin Qian, Zhiming Zhao, Wei Shang, Zhihan Xu, Beibei Zhang, Hui Cai View Abstract ❯
Proteomic analysis of chick retina during early recovery from lens‑induced myopia Yun Yun Zhou, Rachel Ka Man Chun, Jian Chao Wang, Bing Zuo, King Kit Li, Thomas Chuen Lam, Quan Liu, Chi‑Ho To View Abstract ❯
Screening of differentially expressed genes in male idiopathic osteoporosis via RNA sequencing Li Feng, Yan Wang, Jing Zhou, Baofang Tian, Bo Xia View Abstract ❯
CD8+ T cells with high TGF‑β1 expression cause lymph node fibrosis following HIV infection Lei Huang, Jianning Deng, Wen Xu, Hongbo Wang, Lei Shi, Fengyao Wu, Dan Wu, Weimin Nei, Min Zhao, Panyong Mao, Xianzhi Zhou View Abstract ❯
Lysophosphatidic acid enhances neointimal hyperplasia following vascular injury through modulating proliferation, autophagy, inflammation and oxidative stress Xuhui Shen, Jianjun Zou, Fuyong Li, Tianhe Zhang, Tongqi Guo View Abstract ❯
Porphyromonas gingivalis induced inflammatory responses and promoted apoptosis in lung epithelial cells infected with H1N1 via the Bcl‑2/Bax/Caspase‑3 signaling pathway Yongju Chen, Rui Zhou, Zhe Yi, Yonggang Li, Ying Fu, Yibo Zhang, Ping Li, Xin Li, Yaping Pan View Abstract ❯
miR‑23a suppresses pancreatic cancer cell progression by inhibiting PLK‑1 expression Bin Chen, Akao Zhu, Lei Tian, Ying Xin, Xinchun Liu, Yunpeng Peng, Jingjing Zhang, Yi Miao, Jishu Wei View Abstract ❯
Placental protein 14 as a potential biomarker for diagnosis of preterm premature rupture of membranes Yanyun Wang, Haibo Luo, Guanglu Che, Yanqin Li, Jun Gao, Qiongli Yang, Bin Zhou, Linbo Gao, Tao Wang, Yujie Liang, Lin Zhang View Abstract ❯
Genome‑wide DNA methylation profiling in a rat model with vascular dementia Jong‑Min Park, Yoon Ju Kim, Min Kyung Song, Jae‑Min Lee, Youn‑Jung Kim View Abstract ❯
Anti‑metastatic effects of Aidi on human esophageal squamous cell carcinoma by inhibiting epithelial‑mesenchymal transition and angiogenesis Qingtong Shi, Yali Diao, Feng Jin, Zhiyan Ding View Abstract ❯
Alterations in mRNA profiles of trastuzumab‑resistant Her‑2‑positive breast cancer Bin Zhao, Yang Zhao, Yan Sun, Haitao Niu, Long Sheng, Dongfang Huang, Li Li View Abstract ❯
Salidroside inhibits the proliferation and migration of gastric cancer cells via suppression of Src‑associated signaling pathway activation and heat shock protein 70 expression Zhilin Qi, Tuo Tang, Lili Sheng, Yunfei Ma, Yinhua Liu, Liang Yan, Shimei Qi, Liefeng Ling, Yao Zhang View Abstract ❯
Knockdown of Ran GTPase expression inhibits the proliferation and migration of breast cancer cells Chenyi Sheng, Jian Qiu, Yingying Wang, Zhixian He, Hua Wang, Qingqing Wang, Yeqing Huang, Lianxin Zhu, Feng Shi, Yingying Chen, Shiyao Xiong, Zhen Xu, Qichao Ni View Abstract ❯
Immunotherapy by targeting of VGKC complex for seizure control and prevention of cognitive impairment in a mouse model of epilepsy Zhiliang Fan, Xiaojuan Feng, Zhigang Fan, Xingyuan Zhu, Shaohua Yin View Abstract ❯
Apoptosis of CD19+ chimeric antigen receptor T cells after treatment with chemotherapeutic agents Wenfang Yi, Fuyu Pei, Wen Ding, Mo Yang, Guang Lin, Cheng Zhang, Xuedong Wu, Yuelin He, Xiaoqin Feng, Huanying Liu, Zhiyong Peng, Chunfu Li View Abstract ❯
Anesthetic effects of isoflurane and the molecular mechanism underlying isoflurane‑inhibited aggressiveness of hepatic carcinoma Jing Hu, Jingli Hu, Hongmei Jiao, Qingguo Li View Abstract ❯
Actinidia chinensis planch polysaccharide protects against hypoxia‑induced apoptosis of cardiomyocytes in vitro Qiang Wang, Yunfa Xu, Ying Gao, Qi Wang View Abstract ❯
MEF2‑activated long non‑coding RNA PCGEM1 promotes cell proliferation in hormone‑refractory prostate cancer through downregulation of miR‑148a Shibao Zhang, Zongwu Li, Longyang Zhang, Zhonghua Xu View Abstract ❯
Repair of urethral defects by an adipose mesenchymal stem cell‑porous silk fibroin material Binqiang Tian, Lujie Song, Tao Liang, Zuowei Li, Xuxiao Ye, Qiang Fu, Yonghui Li View Abstract ❯
High glucose upregulates myosin light chain kinase to induce microfilament cytoskeleton rearrangement in hippocampal neurons Liying Zhu, Chengcheng Li, Guiqin Du, Meixiu Pan, Guoqi Liu, Wei Pan, Xing Li View Abstract ❯
Detection of miR‑29a in plasma of patients with lumbar spinal stenosis and the clinical significance Genai Zhang, Wenping Zhang, Yu Hou, Yingchun Chen, Jipeng Song, Lixiang Ding View Abstract ❯
A gene interaction network‑based method to measure the common and heterogeneous mechanisms of gynecological cancer Mingyuan Wang, Liping Li, Jinglan Liu, Jinjin Wang View Abstract ❯
Chemoresistance‑related long non‑coding RNA expression profiles in human breast cancer cells Lei Huang, Lihua Zeng, Jiahui Chu, Pengfei Xu, Mingming Lv, Juan Xu, Juan Wen, Wenqu Li, Luyu Wang, Xiaowei Wu, Ziyi Fu, Hui Xie, Shui Wang View Abstract ❯
COL2A1 mutation (c.3508G>A) leads to avascular necrosis of the femoral head in a Chinese family: A case report Fang Liu, Zhizheng Xiong, Qi Liu, Jinxi Hu, Wenhua Li, Na Zhang View Abstract ❯
A novel PNPLA6 compound heterozygous mutation identified in a Chinese patient with Boucher‑Neuhäuser syndrome Ruizhi Zheng, Yaguang Zhao, Jiayu Wu, Yuanmei Wang, Jian‑Ling Liu, Zhi‑Ling Zhou, Xiao‑Tao Zhou, Dan‑Na Chen, Wei‑Hua Liao, Jia‑Da Li View Abstract ❯
EphrinB/EphB signaling contributes to spinal nociceptive processing via calpain‑1 and caspase‑3 Mei Yang, Wei Chen, Yu Zhang, Rui Yang, Yiru Wang, Hongbin Yuan View Abstract ❯
Identification of a 5‑lncRNA signature‑based risk scoring system for survival prediction in colorectal cancer Liqiang Gu, Jun Yu, Qing Wang, Bin Xu, Liechen Ji, Lin Yu, Xipeng Zhang, Hui Cai View Abstract ❯
Dishevelled‑2 modulates osteogenic differentiation of human synovial fibroblasts in osteoarthritis Lihua Zhang, Luan Luan, Yingying Ma View Abstract ❯
Genome‑wide identification of long noncoding RNAs in CCl4‑induced liver fibrosis via RNA sequencing Zhenghua Gong, Jialin Tang, Tianxin Xiang, Jiayu Lin, Chaowen Deng, Yanzhong Peng, Jie Zheng, Guoxin Hu View Abstract ❯
Human HLA‑F adjacent transcript 10 promotes the formation of cancer initiating cells and cisplatin resistance in bladder cancer Chen Li, Zhenfan Wang, Ninghan Feng, Jian Dong, Xiaoyan Deng, Yin Yue, Yuehong Guo, Jianquan Hou View Abstract ❯
Gas‑filled ultrasound microbubbles enhance the immunoactivity of the HSP70‑MAGEA1 fusion protein against MAGEA1‑expressing tumours Xing Gao, Yang Nan, Yuan Yuan, Xue Gong, Yuanyuan Sun, Huihui Zhou, Yujin Zong, Lijun Zhang, Ming Yu View Abstract ❯
α‑synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum‑Golgi compartment Mei Liu, Lixia Qin, Lili Wang, Jieqiong Tan, Hainan Zhang, Jianguang Tang, Xiangmin Shen, Liming Tan, Chunyu Wang View Abstract ❯
Bioinformatics analysis of microarray data to reveal the pathogenesis of brain ischemia Jiaxuan He, Ya Gao, Gang Wu, Xiaoming Lei, Yong Zhang, Weikang Pan, Hui Yu View Abstract ❯
Toll‑Like receptor 4 promotes the phosphorylation of CRMP2 via the activation of Rho‑kinase in MCAO rats Xue‑Bo Li, Ming‑Xia Ding, Chun‑Li Ding, Liang‑Liang Li, Jinzhou Feng, Xiao‑Jun Yu View Abstract ❯
Overexpression of Annexin A1 protects against benzo[a]pyrene‑induced bronchial epithelium injury Yanfei Cui, Shengya Yang View Abstract ❯
miR‑24 regulates angiogenesis in gliomas Dongwei Dai, Wei Huang, Qiong Lu, Hanchun Chen, Jianmin Liu, Bo Hong View Abstract ❯
TRIM24 siRNA induced cell apoptosis and reduced cell viability in human nasopharyngeal carcinoma cells Peng Wang, Na Shen, Danzheng Liu, Xianhui Ning, Daquan Wu, Xinsheng Huang View Abstract ❯
Downregulation of N‑Myc inhibits neuroblastoma cell growth via the Wnt/β‑catenin signaling pathway Yingge Wang, Shan Gao, Weiguang Wang, Yuting Xia, Jingyan Liang View Abstract ❯
Significant role of microRNA‑219‑5p in diabetic retinopathy and its mechanism of action Junying Zhao, Sha Gao, Yanji Zhu, Xi Shen View Abstract ❯
Silencing of URG11 expression inhibits the proliferation and epithelial‑mesenchymal transition in benign prostatic hyperplasia cells via the RhoA/ROCK1 pathway Guanying Zhang, Feng Zhu, Guangye Han, Zeyu Li, Quanfeng Yu, Zhenhui Li, Jianchang Li View Abstract ❯
LIN28A inhibits lysosome‑associated membrane glycoprotein 1 protein expression in embryonic stem and bladder cancer cells Peng Pan, Ting Chen, Yanmin Zhang, Zhengyu Qi, Jie Qin, Guanghui Cui, Xin Guo View Abstract ❯
Anticancer effects of isofraxidin against A549 human lung cancer cells via the EGFR signaling pathway Han Zhang, Qian‑Qian Feng, Jian‑Hua Gong, Jing‑Ping Ma View Abstract ❯
Locomotor activity of rats with SCI is improved by dexmedetomidine by targeting the expression of inflammatory factors Wei‑Guo Wang, Lin Wang, Zhen‑Hua Jiao, Bin Xue, Zhan‑Wang Xu View Abstract ❯
C‑Myc inhibitor 10058‑F4 increases the efficacy of dexamethasone on acute lymphoblastic leukaemia cells Mei Lv, Yi Wang, Wenmiao Wu, Shujun Yang, Huiling Zhu, Bei Hu, Ying Chen, Cong Shi, Yi Zhang, Qitian Mu, Guifang Ouyang View Abstract ❯
Angiotensin II inhibits the protein expression of ZO‑1 in vascular endothelial cells by downregulating VE‑cadherin Longbin Liu, Liping Meng, Peng Zhang, Hui Lin, Jufang Chi, Fang Peng, Hangyuan Guo View Abstract ❯
Identification of a VHL gene mutation in a Chinese family with Von Hippel‑Lindau syndrome Zhengwen He, Lu Xia, Zhiyong Deng, Aojie Lian, Zhengmao Hu, Bin Li View Abstract ❯
miR‑188 suppresses tumor progression by targeting SOX4 in pediatric osteosarcoma Lu Pan, Lingxin Meng, Feng Liang, Li Cao View Abstract ❯
Pulsed electromagnetic fields inhibit osteoclast differentiation in RAW264.7 macrophages via suppression of the protein kinase B/mammalian target of rapamycin signaling pathway Yutian Lei, Jinyu Su, Haixia Xu, Qiang Yu, Ming Zhao, Jing Tian View Abstract ❯
Sevoflurane suppresses proliferation by upregulating microRNA-203 in breast cancer cells Jiaying Liu, Longqiu Yang, Xia Guo, Guangli Jin, Qimin Wang, Dongdong Lv, Junli Liu, Qiu Chen, Qiong Song, Baolin Li View Abstract ❯
Identification of CHCHD2 mutations in patients with Alzheimer's disease, amyotrophic lateral sclerosis and frontotemporal dementia in China Xixi Liu, Bin Jiao, Weiwei Zhang, Tingting Xiao, Lihua Hou, Chuzheng Pan, Beisha Tang, Lu Shen View Abstract ❯
Bioinformatics analysis of key differentially expressed genes in well and poorly differentiated endometrial carcinoma Yuqin Zang, Mengting Dong, Kai Zhang, Wenyan Tian, Yingmei Wang, Fengxia Xue View Abstract ❯
Knockdown of zinc transporter ZIP8 expression inhibits neuroblastoma progression and metastasis in vitro Zhengrong Mei, Pengke Yan, Ying Wang, Shaozhi Liu, Fang He View Abstract ❯
Hyperoside protects human kidney‑2 cells against oxidative damage induced by oxalic acid Yongliang Chen, Lihong Ye, Wangjian Li, Dongzhang Li, Feng Li View Abstract ❯
Effects of obatoclax combined with gemcitabine on the biological activity of pancreatic cancer cells under hypoxic conditions Xin‑Fang Hou, Shuai Li, Chen Wu, Ke Li, Shu‑Ning Xu, Ju‑Feng Wang View Abstract ❯
miR‑486‑5p is upregulated in osteoarthritis and inhibits chondrocyte proliferation and migration by suppressing SMAD2 Junkai Shi, Kansuo Guo, Shile Su, Jun Li, Chunhui Li View Abstract ❯
Exosomal MALAT1 derived from oxidized low-density lipoprotein-treated endothelial cells promotes M2 macrophage polarization Chaoyang Huang, Jie Han, Yutao Wu, Shan Li, Qiwen Wang, Wenjuan Lin , Jianhua Zhu View Abstract ❯
LncRNA TP73‑AS1 predicts poor prognosis and promotes cell proliferation in ovarian cancer via cell cycle and apoptosis regulation Xiuyun Li, Xiaoyan Wang, Li Mao, Shuhong Zhao, Haidong Wei View Abstract ❯
An active component containing pterodontic acid and pterodondiol isolated from Laggera pterodonta inhibits influenza A virus infection through the TLR7/MyD88/TRAF6/NF‑κB signaling pathway Yutao Wang, Jing Li, Wen Yan, Qiaolian Chen, Zhihong Jiang, Rongping Zhang, Xiping Pan, Xinhua Wang View Abstract ❯
Effects of chronic unpredictable mild stress on ovarian reserve in female rats: Feasibility analysis of a rat model of premature ovarian failure Xiao‑Yan Fu, Hao‑Hao Chen, Ning Zhang, Ming‑Xing Ding, Ying‑Er Qiu, Xiao‑Ming Pan, Yuan‑Shu Fang, Yi‑Ping Lin, Qun Zheng, Wen‑Qian Wang View Abstract ❯
Interleukin‑1β‑mediated suppression of microRNA‑27a‑3p activity in human cartilage via MAPK and NF‑κB pathways: A potential mechanism of osteoarthritis pathogenesis Xing Li, Peiheng He, Ziqing Li, Haixing Wang, Minghao Liu, Yinbo Xiao, Dongliang Xu, Yan Kang, Hua Wang View Abstract ❯
Increased expression of microRNA-338-3p contributes to production of Dsg3 antibody in pemphigus vulgaris patients Qingxiu Liu, Feiyi Cui, Menglei Wang, Hao Xiong, Xiaoming Peng, Liuping Liang, Li Li, Jing Zhang, Xuebiao Peng, Kang Zeng View Abstract ❯
Vacquinol‑1 induces apoptosis in hepatocellular carcinoma cell Shu‑Lan Sun, Xiaoxi Li, Nan Su, Shi Chen, Xiaoxin Gao, Guirong Zhang, Haozhe Piao View Abstract ❯
Dextran‑coated superparamagnetic iron oxide nanoparticles activate the MAPK pathway in human primary monocyte cells Qihong Wu, Tianyu Miao, Ting Feng, Chuan Yang, Yingkun Guo, Hong Li View Abstract ❯
Intraperitoneal injection of thalidomide alleviates early osteoarthritis development by suppressing vascular endothelial growth factor expression in mice Jia Lin Song, De Long Li, Hang Fang, Dao Zhang Cai View Abstract ❯
Inhibition of granzyme B activity blocks inflammation induced by lipopolysaccharide through regulation of endoplasmic reticulum stress signaling in NK92 cells Lei Wang, Shaowei Jiang, Ling Xiao, Lin Chen, Yanyan Zhang, Jing Tong View Abstract ❯
Helicobacter pylori infection impairs gastric epithelial barrier function via microRNA‑100‑mediated mTOR signaling inhibition Guimei Hu, Lihua Guo, Guoliang Ye View Abstract ❯
Downregulation of microRNA‑198 suppresses cell proliferation and invasion in retinoblastoma by directly targeting PTEN Dongdong Wei, Yingbin Miao, Lianxia Yu, Degong Wang, Yingli Wang View Abstract ❯
Rs2910164 in microRNA‑146a confers an elevated risk of depression in patients with coronary artery disease by modulating the expression of NOS1 Xinling Zhang, Qianqian Huo, Wei Sun, Chunxiang Zhang, Zongyin Wu, Bing Xing, Qiang Li View Abstract ❯
Quercetin protects against inflammation, MMP‑2 activation and apoptosis induction in rat model of cardiopulmonary resuscitation through modulating Bmi‑1 expression Dawei Wang, Xiaoqian Lou, Xiao‑Ming Jiang, Chenxi Yang, Xiao‑Liang Liu, Nan Zhang View Abstract ❯
Expression analysis of ST3GAL4 transcripts in cervical cancer cells Lorena Roa‑de La Cruz, Patricia Martínez‑Morales, Irene Morán‑Cruz, Lorena Milflores‑Flores, Nora Rosas‑Murrieta, César González‑Ramírez, Claudia Ortiz‑Mateos, Ricardo Monterrosas‑Santamaría, Celestina González‑Frías, Carlos Rodea‑Ávila, Teresa Apresa‑García, Adriana Aguilar‑Lemarroy, Luis Jave‑Suarez, Gerardo Santos‑López, Julio Reyes‑Leyva, Verónica Vallejo‑Ruiz View Abstract ❯
Andrographolide affects Th1/Th2/Th17 responses of peripheral blood mononuclear cells from ulcerative colitis patients Qin Zhu, Peifen Zheng, Jianying Zhou, Xinyu Chen, Yuliang Feng, Weifeng Wang, Feng Zhou, Qiaona He View Abstract ❯
Effects of intravenous anesthetics on the phosphorylation of cAMP response element‑binding protein in hippocampal slices of adult mice Haiying Gao, Lingyu Zhang, Zhenyi Chen, Shuncui Liu, Qinghong Zhang, Bingxi Zhang View Abstract ❯
Computational modeling and biomarker studies of pharmacological treatment of Alzheimer's disease (Review) Mubashir Hassan, Qamar Abbas, Sung‑Yum Seo, Saba Shahzadi, Hany Al Ashwal, Nazar Zaki, Zeeshan Iqbal, Ahmed A. Moustafa View Abstract ❯
Research progress on human genes involved in the pathogenesis of glaucoma (Review) Hong‑Wei Wang, Peng Sun, Yao Chen, Li‑Ping Jiang, Hui‑Ping Wu, Wen Zhang, Feng Gao View Abstract ❯
Molecular mechanisms of autophagy in cardiac ischemia/reperfusion injury (Review) Xiao‑Long Lin, Wei‑Jin Xiao, Le‑Le Xiao, Mi‑Hua Liu View Abstract ❯
Propranolol induces hemangioma endothelial cell apoptosis via a p53‑BAX mediated pathway Tian‑Hua Yao, Parekejiang Pataer, Krishna Prasad Regmi, Xi‑Wen Gu, Quan‑Yan Li, Jing‑Ting Du, Su‑Meng Ge, Jun‑Bo Tu View Abstract ❯
Competing endogenous RNA regulatory network in papillary thyroid carcinoma Shouhua Chen, Xiaobin Fan, He Gu, Lili Zhang, Wenhua Zhao View Abstract ❯
Candesartan targeting of angiotensin II type 1 receptor demonstrates benefits for hypertension in pregnancy via the NF‑κB signaling pathway Xudong Zhao, Xietong Wang View Abstract ❯
PYGB siRNA inhibits the cell proliferation of human osteosarcoma cell lines Shuwei Zhang, Yichi Zhou, Yuanyu Zha, Yang Yang, Linlong Wang, Jingfeng Li, Wei Jin View Abstract ❯
Effect of co‑culture with amniotic epithelial cells on the biological characteristics of amniotic mesenchymal stem cells Li‑Jing Ran, Yun Zeng, Shao‑Chun Wang, Di‑Si Zhang, Min Hong, Shao‑You Li, Jian Dong, Ming‑Xia Shi View Abstract ❯
Lysine‑specific demethylase 2 contributes to the proliferation of small cell lung cancer by regulating the expression of TFPI‑2 Yunfeng Cao, Chunhui Guo, Yanhai Yin, Xin Li, Ling Zhou View Abstract ❯
Bioinformatic analyses reveal the key pathways and genes in the CXCR4 mediated mesenchymal subtype of glioblastoma Li Yi, Luqing Tong, Tao Li, Long Hai, Iruni Roshanie Abeysekera, Zhennan Tao, Haiwen Ma, Peidong Liu, Yang Xie, Jiabo Li, Feng Yuan, Shengping Yu, Xuejun Yang View Abstract ❯
Transcriptome sequencing analysis reveals the effect of combinative treatment with low‑intensity pulsed ultrasound and magnesium ions on hFOB1.19 human osteoblast cells Haiyue Zu, Xueting Yi, Dewei Zhao View Abstract ❯
Capturing antibacterial natural products with in silico techniques Mahmud Masalha, Mahmoud Rayan, Azmi Adawi, Ziyad Abdallah, Anwar Rayan View Abstract ❯
A novel anti‑proliferative pentapeptide (ILYMP) isolated from Cyclina sinensis protein hydrolysate induces apoptosis of DU‑145 prostate cancer cells Fangmiao Yu, Yaru Zhang, Lei Ye, Yunping Tang, Guofang Ding, Xiaojun Zhang, Zuisu Yang View Abstract ❯
LncRNA WWOX‑AS1 inhibits the proliferation, migration and invasion of osteosarcoma cells Gang Qu, Zhiqiang Ma, Wenxian Tong, Jiahui Yang View Abstract ❯
Rosuvastatin relieves myocardial ischemia/reperfusion injury by upregulating PPAR‑γ and UCP2 Ling Wang, Rong Lin, Langtao Guo, Meiman Hong View Abstract ❯
Quercetin protects against ox‑LDL‑induced injury via regulation of ABCAl, LXR‑α and PCSK9 in RAW264.7 macrophages Shanshan Li, Hui Cao, Dingzhu Shen, Qingling Jia, Chuan Chen, San Li Xing View Abstract ❯
Bidirectional modulation of insulin action by reactive oxygen species in 3T3‑L1 adipocytes Mingfeng Ma, Yingyao Quan, Yong Li, Xu He, Jing Xiao, Meixiao Zhan, Wei Zhao, Yongjie Xin, Ligong Lu, Liangping Luo View Abstract ❯
Hypothermic machine perfusion attenuates ischemia/reperfusion injury against rat livers donated after cardiac death by activating the Keap1/Nrf2‑ARE signaling pathway Shuai Xue, Weiyang He, Xianpeng Zeng, Zimei Tang, Shoucheng Feng, Zibiao Zhong, Yan Xiong, Yanfeng Wang, Qifa Ye View Abstract ❯
Inhibitory effects of silybin on the efflux pump of methicillin‑resistant Staphylococcus aureus Di Wang, Kunpeng Xie, Dan Zou, Meizhu Meng, Mingjie Xie View Abstract ❯
Identification of key gene networks associated with fracture healing using αSMA‑labeled progenitor cells Hua Wang, Yongxiang Wang, Jinshan He, Chunyu Diao, Junying Sun, Jingcheng Wang View Abstract ❯
In vivo antitumor activity of liposome‑plasmid DNA encoding mutant survivin‑T34A in cervical cancer Fang Qiu, Xia Zhao View Abstract ❯
Downregulation of microRNA‑449a‑5p promotes esophageal squamous cell carcinoma cell proliferation via cyclin D1 regulation Tao Jiang, Junfeng Liu, Jixing Mu View Abstract ❯
Downregulation of CUEDC2 prevents doxorubicin‑induced cardiotoxicity in H9c2 cells Xianpu Zhang, Jiaojiao Li, Yongbo Cheng, Jianguang Yi, Xin Liu, Wei Cheng View Abstract ❯
Time‑dependent and independent effects of thyroid hormone administration following myocardial infarction in rats Ioanna Iliopoulou, Iordanis Mourouzis, George I. Lambrou, Dimitra Iliopoulou, Dimitrios‑Dionysios Koutsouris, Constantinos Pantos View Abstract ❯
Two rare missense mutations in the fibrillin‑1 gene associated with atypical cardiovascular manifestations in a Chinese patient affected by Marfan syndrome Miao Zhang, Yaqi Zhou, Yang Peng, Lijun Jin View Abstract ❯
RNA‑sequencing analysis of aberrantly expressed long non‑coding RNAs and mRNAs in a mouse model of ventilator‑induced lung injury Bo Xu, Yizhou Wang, Xiujuan Li, Yanfei Mao, Xiaoming Deng View Abstract ❯
Endothelial cells and endothelin‑1 promote the odontogenic differentiation of dental pulp stem cells Mingyue Liu, Lin Zhao, Junlong Hu, Lihua Wang, Ning Li, Di Wu, Xin Shi, Mengtong Yuan, Weiping Hu, Xiaofeng Wang View Abstract ❯
Inhibition of microRNA‑16 protects mesenchymal stem cells against apoptosis Jiang Rui, Shaohong Fang, Yongchen Wang, Bo Lv, Bo Yu, Shufeng Li View Abstract ❯
Matrine inhibits the invasive and migratory properties of human hepatocellular carcinoma by regulating epithelial‑mesenchymal transition Yuwen Wang, Shujun Zhang, Jia Liu, Biaobiao Fang, Jie Yao, Binglin Cheng View Abstract ❯
Regulatory effects of miRNA‑181a on FasL expression in bone marrow mesenchymal stem cells and its effect on CD4+T lymphocyte apoptosis in estrogen deficiency‑induced osteoporosis Bingyi Shao, Xiaohui Fu, Yang Yu, Deqin Yang View Abstract ❯
RNAi‑mediated downregulation of asparaginase‑like protein 1 inhibits growth and promotes apoptosis of human cervical cancer line SiHa Xiao‑Feng Lv, Han‑Qing Hong, Ling Liu, Shi‑Hong Cui, Chen‑Chen Ren, Hong‑Yu Li, Xiao‑An Zhang, Lin‑Dong Zhang, Tian‑Xiang Wei, Jin‑Jin Liu, Wen‑Ying Xing, Han Fu, Shu‑Jun Yan View Abstract ❯
Apoptosis induced by 9,11‑dehydroergosterol peroxide from Ganoderma Lucidum mycelium in human malignant melanoma cells is Mcl‑1 dependent Lin Zheng, Yum‑Shing Wong, Mumin Shao, Shiying Huang, Fochang Wang, Jianping Chen View Abstract ❯
Matrine inhibits prostate cancer via activation of the unfolded protein response/endoplasmic reticulum stress signaling and reversal of epithelial to mesenchymal transition Junli Chang, Shaopu Hu, Wenyi Wang, Yimian Li, Wenlan Zhi, Sheng Lu, Qi Shi, Yongjun Wang, Yanping Yang View Abstract ❯
Antitumor effect of lapatinib and cytotoxic agents by suppression of E2F1 in HER2‑positive breast cancer Akiko Matsumoto, Tetsu Hayashida, Maiko Takahashi, Hiromitsu Jinno, Yuko Kitagawa View Abstract ❯
Inhibitory roles of miR‑9 on papillary thyroid cancer through targeting BRAF Yi Gu, Nan Yang, Leping Yin, Chao Feng, Tong Liu View Abstract ❯
Dioscin protects against coronary heart disease by reducing oxidative stress and inflammation via Sirt1/Nrf2 and p38 MAPK pathways Bo Yang, Bin Xu, Hua Zhao, Ya‑Bin Wang, Jian Zhang, Chuan‑Wei Li, Qing Wu, Yu‑Kang Cao, Yang Li, Feng Cao View Abstract ❯
Application of an improved targeted next generation sequencing method to diagnose non‑syndromic mental retardation in one step: A case report Weipeng Wang, Bing Mao, Xiaoming Wei, Dan Yin, Hui Li, Liangwei Mao, Xueqin Guo, Yan Sun, Yun Yang View Abstract ❯
Identification of a mutL‑homolog 1 mutation via whole‑exome sequencing in a Chinese family with Gardner syndrome Zilan Lv, Chuan Wang, Lixiang Wu, Bianqin Guo, Darong Zhang, Yang Zhang, Shengxing Huang, Minglin Ou View Abstract ❯
Water‑soluble nano‑pearl powder promotes MC3T3‑E1 cell differentiation by enhancing autophagy via the MEK/ERK signaling pathway Yanan Cheng, Wenbai Zhang, Hui Fan, Pu Xu View Abstract ❯
Concomitant presence of JAK2V617F mutation and BCR‑ABL translocation in two patients: A new entity or a variant of myeloproliferative neoplasms (Case report) Filipa Mousinho, Ana P. Azevedo, Tatiana Mendes, Paula Sousa E Santos, Rita Cerqueira, Sónia Matos, Sónia Santos, Sância Ramos, João Faro Viana, Fernando Lima View Abstract ❯
Resveratrol inhibits angiotensin II‑induced proliferation of A7r5 cells and decreases neointimal hyperplasia by inhibiting the CaMKII‑HDAC4 signaling pathway Xiaozhen Lin, Chuanfang Cheng, Junyang Zhong, Benrong Liu, Chengfeng Luo, Wenchao Ou, Pei Mo, Qiang Huang, Shiming Liu View Abstract ❯
Munc13‑4 mediates human neutrophil elastase‑induced airway mucin5AC hypersecretion by interacting with syntaxin2 Rui Xu, Jia Zhou, Xiang‑Dong Zhou, Qi Li, Juliy M. Perelman, Victor P. Kolosov View Abstract ❯
Acid fibroblast growth factor facilitates the progression of atherosclerotic plaques regardless of alterations in serum lipid expression levels in HFD‑fed ApoE‑/‑ mice Jibo Han, Yao Du, Lintao Wang, Xiong Chen, Liqin Jiang, Jianjiang Xu View Abstract ❯
Novel CTCF mutations in Chinese patients with ovarian endometriosis Jiubai Guo, Bianna Cao, Xiaoyun Xu, Fei Wu, Bin Zhu View Abstract ❯
Diagnosis of polyglutamine spinocerebellar ataxias by polymerase chain reaction amplification and Sanger sequencing Changqiang Chen, Xuqian Fang, Shunchang Sun View Abstract ❯
Effect of hesperetin derivatives on the development of selenite‑induced cataracts in rats Yosuke Nakazawa, Martin Pauze, Kazuya Fukuyama, Noriaki Nagai, Megumi Funakoshi‑Tago, Takeshi Sugai, Hiroomi Tamura View Abstract ❯
TLR4/PKCα/occludin signaling pathway may be related to blood‑brain barrier damage Zhixian Tang, Dan Guo, Liang Xiong, Bing Wu, Xuehua Xu, Jinfeng Fu, Liyun Kong, Ziyou Liu, Chunfa Xie View Abstract ❯
Atorvastatin protects BV‑2 mouse microglia and hippocampal neurons against oxygen‑glucose deprivation‑induced neuronal inflammatory injury by suppressing the TLR4/TRAF6/NF‑κB pathway Jian Han, Qi‑Hua Yin, Yang Fang, Wei‑Qing Shou, Cong‑Cong Zhang, Fu‑Qiang Guo View Abstract ❯
Caspase‑9 was involved in cell apoptosis in human dental pulp stem cells from deciduous teeth Hong Qian, Qun Huang, Yu‑Xiang Chen, Qiong Liu, Jing‑Xian Fang, Man‑Wen Ye View Abstract ❯
Spinal glucocorticoid receptor‑regulated chronic morphine tolerance may be through extracellular signal‑regulated kinase 1/2 Mei‑Li Zhai, Yi Chen, Chong Liu, Jian‑Bo Wang, Yong‑Hao Yu View Abstract ❯
Free‑floating cancer cells in lymph node sinuses of hilar lymph node‑positive patients with non‑small cell lung cancer Yusuke Nakamura, Masaya Mukai, Shinichiro Hiraiwa, Kyoko Kishima, Tomoko Sugiyama, Takuma Tajiri, Shunsuke Yamada, Masayuki Iwazaki View Abstract ❯
Rapamycin and ZSTK474 can have differential effects at different post‑infection time‑points regarding CVB3 replication and CVB3‑induced autophagy Huan Chang, Lang Tian, Jia Chen, Anliu Tang, Chunyun Li, Zhuoying Li, Zuocheng Yang View Abstract ❯
Cryptotanshinone inhibits IgE‑mediated degranulation through inhibition of spleen tyrosine kinase and tyrosine‑protein kinase phosphorylation in mast cells Sumiyasuren Buyanravjikh, Sora Han, Sunyi Lee, Ae Lee Jeong, Hye In Ka, Ji Young Park, Ariundavaa Boldbaatar, Jong‑Seok Lim, Myeong‑Sok Lee, Young Yang View Abstract ❯
Baicalein inhibits osteosarcoma cell proliferation and invasion through the miR‑183/Ezrin pathway Jian Zhang, Wei Yang, You‑Bing Zhou, Yong‑Xiao Xiang, Lu‑Shan Wang, Wen‑Kai Hu, Wen‑Jun Wang View Abstract ❯
Pien Tze Huang ameliorates DSS‑induced colonic inflammation in a mouse colitis model through inhibition of the IL‑6/STAT3 pathway Li Li, Aling Shen, Jianfeng Chu, Thomas J. Sferra, Senthilkumar Sankararaman, Xiao Ke, Youqin Chen, Jun Peng View Abstract ❯
MicroRNA‑663b mediates TAM resistance in breast cancer by modulating TP73 expression Hua Jiang, Lin Cheng, Pan Hu, Renbin Liu View Abstract ❯
Pulsed electromagnetic fields alleviate streptozotocin‑induced diabetic muscle atrophy Jin Yang, Lijun Sun, Xiushan Fan, Bo Yin, Yiting Kang, Shucheng An, Liang Tang View Abstract ❯
Downregulation of miR‑135a predicts poor prognosis in acute myeloid leukemia and regulates leukemia progression via modulating HOXA10 expression Hongwei Xu, Quan Wen View Abstract ❯
G protein‑coupled estrogen receptor/miR‑148a/human leukocyte antigen‑G signaling pathway mediates cell apoptosis of ovarian endometriosis Shun Zhi He, Jing Li, Hong Chu Bao, Mei Mei Wang, Xin Rong Wang, Xin Huang, Feng Hua Li, Wei Zhang, An Li Xu, Hao Cui Fang, Yang Xing Sheng View Abstract ❯
Therapeutic effect of the natural compounds baicalein and baicalin on autoimmune diseases Jian Xu, Jinlong Liu, Guolin Yue, Mingqiang Sun, Jinliang Li, Xia Xiu, Zhenzhong Gao View Abstract ❯
MicroRNA‑433 reduces cell proliferation and invasion in non‑small cell lung cancer via directly targeting E2F transcription factor 3 Nian Liu, Zhiguang Liu, Weidong Zhang, Yang Li, Jun Cao, Huan Yang, Xiuying Li View Abstract ❯
Cyclin‑dependent kinase 10 prevents glioma metastasis via modulation of Snail expression Hui Li, Yanjie You, Jianfeng Liu View Abstract ❯
Expression of microRNA‑377 and microRNA‑192 and their potential as blood‑based biomarkers for early detection of type 2 diabetic nephropathy Ghada Al‑Kafaji, Haifa Abdulla Al‑Muhtaresh View Abstract ❯
Upregulation of microRNA‑24 causes vasospasm following subarachnoid hemorrhage by suppressing the expression of endothelial nitric oxide synthase Huan‑Ting Li, Jing Wang, Shi‑Fang Li, Lei Cheng, Wan‑Zhong Tang, Yu‑Gong Feng View Abstract ❯
MicroRNA‑874 inhibits proliferation and invasion of pancreatic ductal adenocarcinoma cells by directly targeting paired box 6 Jiandong Diao, Xiaoyun Su, Ling Cao, Yongjing Yang, Yanling Liu View Abstract ❯
Red mulberry fruit aqueous extract and silk proteins accelerate acute ethanol metabolism and promote the anti‑oxidant enzyme systems in rats Hye Jeong Yang, Min Jung Kim, Eun Seon Kang, Da Sol Kim, Sunmin Park View Abstract ❯
VHL loss predicts response to Aurora kinase A inhibitor in renal cell carcinoma cells Xiao‑Fei Ding, Jun Zhou, Guang Chen, Ying‑Liang Wu View Abstract ❯

20-22 September, 2018, Metropolitan Hotel, Athens, Greece 23nd World Congress on Advances in Oncology & 22th International Symposium on Molecular Medicine 18-19 September 2018, Pre-Congress Workshop: 'MicroRNA Analysis'

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