The role of Hipk2-p53 pathways in arsenic-induced autistic behaviors: A translational study from rats to humans

2020 ◽  
Vol 267 ◽  
pp. 115568
Author(s):  
Hao Zhou ◽  
Yan Lin ◽  
Weiqing Zhao ◽  
Yanbo Teng ◽  
Yuxia Cui ◽  
...  
Keyword(s):  
Translational Study ◽  
Autistic Behaviors

scholarly journals Bilateral but not unilateral subthalamic stimulation promotes apathy: a translational study in rodents and Parkinson’s disease patients

2020 ◽  
Author(s):  
Yvan Vachez ◽  
Marie Bahout ◽  
Robin Magnard ◽  
Pierre-Maxime David ◽  
Carole Carcenac ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Acute Effect ◽  
Recent Experimental Data ◽  
Translational Study ◽  
Clinical Center ◽  
Subthalamic Stimulation ◽  
Operative Assessment ◽  
Stn Dbs

ABSTRACTApathy is frequently reported in Parkinson’s disease (PD) patients under subthalamic nucleus deep brain stimulation (STN-DBS). The prevailing clinical view for apathy following STN-DBS is the reduction of dopaminergic medication. However, few clinical reports and recent experimental data suggested the pathogenicity of bilateral STN-DBS on motivation, challenging the leading opinion. Here, we investigate whether bilateralism of STN-DBS influences apathy outcome after STN-DBS, combining pre-clinical and clinical approaches. We assess the motivational effects of chronic unilateral STN-DBS in rats in the exact same conditions having highlighted a loss of motivation under bilateral STN-DBS. Clinical data are obtained by the follow-up of a cohort of parkinsonian patients undergoing unilateral STN-DBS and coming from the clinical center that described apathy related to bilateral STN-DBS itself. Despite an acute effect, which fades rapidly, unilateral STN-DBS did not induce a loss of motivation reminiscent to apathy in rats. In patients, apathy did not increase between the preoperative and the post-operative assessment. Together, those data demonstrate that bilateral but not unilateral STN-DBS can induce a loss of motivation in both rats and patients. This constitutes another evidence of the role of STN-DBS itself for apathy in PD.

scholarly journals Prognostic role of microRNA polymorphisms in advanced gastric cancer: a translational study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

2013 ◽  
Vol 24 (10) ◽  
pp. 2581-2588 ◽  
Author(s):  
L. Stenholm ◽  
J. Stoehlmacher-Williams ◽  
S.E. Al-Batran ◽  
N. Heussen ◽  
S. Akin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Prognostic Role ◽  
Translational Study

scholarly journals 621: NOVEL ROLE OF ZONULIN IN THE PATHOPHYSIOLOGY OF GASTRIC MOTILITY: A CLINICAL-TRANSLATIONAL STUDY

2021 ◽  
Vol 50 (1) ◽  
pp. 303-303
Author(s):  
Enid Martinez ◽  
Jinggang Lan ◽  
Alba Miranda-Ribera ◽  
Maria Fiorentino ◽  
Nilesh Mehta ◽  
...  
Keyword(s):  
Gastric Motility ◽  
Translational Study

scholarly journals Long Non-Coding RNA GAS5 and Intestinal MMP2 and MMP9 Expression: A Translational Study in Pediatric Patients with IBD

2019 ◽  
Vol 20 (21) ◽  
pp. 5280 ◽  
Author(s):  
Marianna Lucafò ◽  
Letizia Pugnetti ◽  
Matteo Bramuzzo ◽  
Debora Curci ◽  
Alessia Di Silvestre ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Tissue Injury ◽  
Taqman Assay ◽  
Translational Study ◽  
Non Coding Rna ◽  
New Information ◽  
Mmp9 Expression ◽  
Long Non Coding Rna

Background: The long non-coding RNA (lncRNA) growth arrest–specific transcript 5 (GAS5) seems to be involved in the regulation of mediators of tissue injury, in particular matrix metalloproteinases (MMPs), implicated in the pathogenesis of inflammatory bowel disease (IBD). We investigated the role of GAS5 in regulating MMP2 and MMP9 expression in pediatric patients with IBD and in vitro. Methods: In total, 25 IBD patients were enrolled: For each patient paired inflamed and non-inflamed biopsies were collected. RNA was extracted and GAS5, MMP2, and MMP9 were quantified by TaqMan assay. The expression of GAS5 and MMPs was also determined in the human monocytic THP1 cells differentiated into macrophages and stimulated with lipopolysaccharide (LPS). The function of GAS5 was assessed by overexpressing the lncRNA and evaluating the MMPs levels. Results: Real-time PCR results demonstrated a downregulation of GAS5 and an upregulation of both MMPs in inflamed tissues. In vitro data confirmed the trend observed in patients for the three genes: The stimulation with LPS promoted a downregulation of GAS5 while an increase of MMPs was observed. Overexpression experiments showed that higher levels of GAS5 lead to a decrease of both enzymes. Conclusion: These results provide new information about the role of GAS5 in IBD: The lncRNA could mediate tissue damage by modulating the expression of MMPs.

scholarly journals Novel role of zonulin in the pathophysiology of gastro-duodenal transit: a clinical and translational study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Enid E. Martinez ◽  
Jinggang Lan ◽  
Takumi Konno ◽  
Alba Miranda-Ribera ◽  
Maria Fiorentino ◽  
...  
Keyword(s):  
Mouse Model ◽  
Mrna Expression ◽  
Gastric Motility ◽  
Fluorescein Isothiocyanate ◽  
Time Dependent ◽  
Dependent Manner ◽  
Translational Study ◽  
Duodenal Motility ◽  
Protein Levels

AbstractWe examined the relationship between zonulin and gastric motility in critical care patients and a translational mouse model of systemic inflammation. Gastric motility and haptoglobin (HP) 2 isoform quantification, proxy for zonulin, were examined in patients. Inflammation was triggered by lipopolysaccharide (LPS) injection in C57Bl/6 zonulin transgenic mouse (Ztm) and wildtype (WT) mice as controls, and gastro-duodenal transit was examined by fluorescein-isothiocyanate, 6 and 12 h after LPS-injection. Serum cytokines and zonulin protein levels, and zonulin gastric-duodenal mRNA expression were examined. Eight of 20 patients [14 years, IQR (12.25, 18)] developed gastric dysmotility and were HP2 isoform-producing. HP2 correlated with gastric dysmotility (r = − 0.51, CI − 0.81 to 0.003, p = 0.048). LPS injection induced a time-dependent increase in IL-6 and KC-Gro levels in all mice (p < 0.0001). Gastric dysmotility was reduced similarly in Ztm and WT mice in a time-dependent manner. Ztm had 16% faster duodenal motility than WT mice 6H post-LPS, p = 0.01. Zonulin mRNA expression by delta cycle threshold (dCT) was higher in the stomach (9.7, SD 1.4) than the duodenum (13.9, SD 1.4) 6H post-LPS, p = 0.04. Serum zonulin protein levels were higher in LPS-injected mice compared to vehicle-injected animals in a time-dependent manner. Zonulin correlated with gastric dysmotility in patients. A mouse model had time-dependent gastro-duodenal dysmotility after LPS-injection that paralleled zonulin mRNA expression and protein levels.

scholarly journals Molecular Advances in Hypertension and Blood

2021 ◽  
Vol 23 (1) ◽  
pp. 278
Author(s):  
Eleni Gavriilaki ◽  
Eugenia Gkaliagkousi
Keyword(s):  
Cardiovascular Risk ◽  
Hematopoietic Cell Transplantation ◽  
Unmet Needs ◽  
In Vitro Study ◽  
Special Issue ◽  
Translational Study ◽  
Coagulant Activity ◽  
Continuous Progress

Hematopoietic cells and their microvesicles have recently emerged as novel markers of cardiovascular risk. The crosstalk between these vesicles and endothelial dysfunction or vascular damage is a field of continuous progress. Additionally, thromboinflammation represents an emerging concept in cardiovascular diseases. In hypertension, the role of signaling pathways in hypertension remains also under investigation. Realizing the unmet needs of increased awareness of treating physicians and active researchers in this complex setting, we launched our Special Issue on “Molecular Advances in Hypertension and Blood”. Our issue has addressed both sides of the coin by publishing four articles that are summarized in this editorial. Firstly, we published an experimental study providing evidence that certain molecular pathways may be involved in myocardial remodeling in the settings of arterial hypertension and chronic kidney disease. Secondly, an in vitro study revealed a novel immune-modulatory effect of Ticagrelor, which is widely used in patients with hypertension and cardiovascular disease. Thirdly, another translational study assessed endothelial injury and pro-coagulant activity using circulating microvesicles in survivors of allogeneic hematopoietic cell transplantation, compared to a control population matched for traditional cardiovascular risk factors. Lastly, a review article delineated the role of Toll-like receptors in the pathogenesis of essential hypertension.

scholarly journals Role of TLR4 in the gut-brain axis in Parkinson’s disease: a translational study from men to mice

Gut ◽  
2018 ◽  
Vol 68 (5) ◽  
pp. 829-843 ◽  
Author(s):  
Paula Perez-Pardo ◽  
Hemraj B Dodiya ◽  
Phillip A Engen ◽  
Christopher B Forsyth ◽  
Andrea M Huschens ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Motor Dysfunction ◽  
Brain Inflammation ◽  
Translational Study ◽  
Colonic Biopsy ◽  
Rotenone Treatment

ObjectiveRecent evidence suggesting an important role of gut-derived inflammation in brain disorders has opened up new directions to explore the possible role of the gut-brain axis in neurodegenerative diseases. Given the prominence of dysbiosis and colonic dysfunction in patients with Parkinson’s disease (PD), we propose that toll-like receptor 4 (TLR4)-mediated intestinal dysfunction could contribute to intestinal and central inflammation in PD-related neurodegeneration.DesignTo test this hypothesis we performed studies in both human tissue and a murine model of PD. Inflammation, immune activation and microbiota composition were measured in colonic samples from subjects with PD and healthy controls subjects and rotenone or vehicle-treated mice. To further assess the role of the TLR4 signalling in PD-induced neuroinflammation, we used TLR4-knockout (KO) mice in conjunction with oral rotenone administration to model PD.ResultsPatients with PD have intestinal barrier disruption, enhanced markers of microbial translocation and higher pro-inflammatory gene profiles in the colonic biopsy samples compared with controls. In this regard, we found increased expression of the bacterial endotoxin-specific ligand TLR4, CD3+ T cells, cytokine expression in colonic biopsies, dysbiosis characterised by a decrease abundance of SCFA-producing colonic bacteria in subjects with PD. Rotenone treatment in TLR4-KO mice revealed less intestinal inflammation, intestinal and motor dysfunction, neuroinflammation and neurodegeneration, relative to rotenone-treated wild-type animals despite the presence of dysbiotic microbiota in TLR4-KO mice.ConclusionTaken together, these studies suggest that TLR4-mediated inflammation plays an important role in intestinal and/or brain inflammation, which may be one of the key factors leading to neurodegeneration in PD.

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