scholarly journals Les anti-TNF-α pour le traitement des uvéites non infectieuses

2020 ◽  
Vol 36 (10) ◽  
pp. 893-899
Author(s):  
Florence Hoogewoud ◽  
Laura Kowalczuk ◽  
Elodie Bousquet ◽  
Antoine Brézin ◽  
Elodie Touchard ◽  
...  
Keyword(s):  
Effets Indésirables ◽  
Tnf Α ◽  
Thérapie Génique ◽  
Neuro Inflammation

Les molécules anti-TNF-α administrés par voie générale ont été approuvés récemment pour le traitement des uvéites non inflammatoires, élargissant l’arsenal thérapeutique dans le traitement de ces pathologies responsables de cécité évitable si l’inflammation est contrôlée. Quand seul l’œil est atteint, des stratégies d’administration locale permettraient d’optimiser les effets intraoculaires des molécules anti-TNF-α et d’en réduire les effets indésirables. Une nouvelle méthode de thérapie génique non virale, actuellement en développement, pourrait élargir les indications des molécules anti-TNF-α oculaires, non seulement pour les uvéites, mais également pour d’autres maladies dans lesquelles une neuro-inflammation impliquant le TNF-α a été démontrée.

scholarly journals Peripheral Inflammatory Biomarkers of Methamphetamine Withdrawal Patients Based on the Neuro-Inflammation Hypothesis: The Possible Improvement Effect of Exercise

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingsong Wang ◽  
Chunxia Lu ◽  
Lan Zheng ◽  
Jun Zhang
Keyword(s):  
Resistance Training ◽  
Drug Use ◽  
Exercise Group ◽  
Control Group ◽  
Peripheral Inflammation ◽  
Analog Scale ◽  
Withdrawal Time ◽  
Tnf Α ◽  
Improvement Effect ◽  
Neuro Inflammation

Methamphetamine (MA) induced addiction and neuroinflammation has been implicated. Based on the neuroinflammation hypothesis, this study aims to investigate how exercise influences the craving of patients in MA withdrawal, and explore the mechanism of peripheral inflammation. A total of 90 patients in MA withdrawal were recruited. No difference was noted in the number of years of drug use and the frequency of drug use among patients, and the withdrawal time was within 2 months. The subjects were grouped based on the degree of craving induced by the cues: non-craving control group (NCC group), craving control group (CC group), and craving exercise group (CE group). The CE group was subjected to aerobic combined resistance training. Then, the ELISA method was used to detect plasma IL-6, TNF-α, and IL-1β concentrations; Visual Analog Scale (VAS) measurement of cue-induced cravings under Virtual Reality (VR) exposure (VR-VAS) and the Desires for Drug Questionnaire (DDQ) were used to assess cravings. Consequently, plasma IL-6, TNF-α, IL-1β, levels, and the VR-VAS and DDQ scores of MA withdrawal patients were significantly reduced after exercise. This study confirmed that 8 weeks of incremental load aerobic combined with resistance training reduces peripheral inflammation and significantly reduces the level of craving for MA.

scholarly journals In Silico, in Vitro and in Vivo Investigation of a Newly Synthesized Ionic Compound As Anti-Alzheimer Multi-Target Dual AChE/BuChE Inhibitor Possessing Neuro-Protective Effects Against Aβ Induced Neurotoxicity in PC12 Cells and Alzheimer Rat Model

2021 ◽  
Author(s):  
Hosna Karami ◽  
somaieh soltani ◽  
Gerhard Wolber ◽  
Saeed Sadigh-Eteghad ◽  
Roghaye Nikbakht ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Quaternary Ammonium ◽  
Aqueous Solubility ◽  
In Vivo Studies ◽  
Protective Effects ◽  
Rat Models ◽  
Tnf Α ◽  
Neuro Inflammation

Abstract Multi-target anti Alzheimer’s disease (AD) compounds are promising leads for the development of AD modifying agents. Ionic compounds containing quaternary ammonium moiety were synthesized and their multi-targeted anti-AD effects were examined in the current study. Compound 5g possessed suitable aqueous solubility and cell toxicity. It also showed non-competitive dual hAChE/hBuChE inhibition activity. Compound 5g reversed the Aβ-treated PC12 cells’ morphology alteration and reduced PC12 cells’ death. Compound 5g possessed anti-oxidative stress activity through anti-oxidant, anti-ROS production and anti-lipid peroxidation mechanisms. It also reduced the expression of IL-1β and TNF-α genes. Furthermore, compound 5g LDH inhibition, reduction of neuro-inflammation and prevention of autophagy-apoptosis were approved by the results of in vitro studies. Compound 5g delivery to brain was confirmed by in vivo studies. Administration of compound 5g to Aβ-induced AD rat models improved their cognition function and spatial memory learning behavior. TNF-α and NFkB down-regulated in compound 5g treated AD rats’ hippocamp. Besides, compound 5g reversed the up-regulation of AChE in Aβ treated rats’ hippocamp. Molecular modeling studies confirmed the interaction of compound 5g with both steric and catalytic sites of ChE enzymes. The newly synthesized quaternary ammonium containing derivative (compound 5g) possessed multi-target anti-AD efficacy based on in vitro and in vivo studies and its efficacy in AD rat models were approved by behavioral and molecular investigations.

Upregulated Long Non-coding RNA ALMS1-IT1 Promotes Neuroinflammation by Activating NF-κB Signaling in Ischemic Cerebral Injury

2021 ◽  
Vol 27 ◽  
Author(s):  
Peng Lu ◽  
Ye Zhang ◽  
Huanjiang Niu ◽  
Yirong Wang
Keyword(s):  
Inflammatory Cytokines ◽  
Nuclear Translocation ◽  
Cell Model ◽  
Intrathecal Injection ◽  
Cerebral Injury ◽  
Aberrant Expression ◽  
Tnf Α ◽  
Neuro Inflammation ◽  
Pro Inflammatory Cytokines ◽  
Brain Tissues

Background: ALMS1-IT1, a recently identified lncRNA, has been proven to play a crucial role in regulating tumor progression and predicting the survival time of tumor patients. Data analysis from the Human Body Map (HBM) revealed that ALMS1-IT1 is expressed mainly in brain tissues. Methods: In this study, the role of ALMS1-IT in regulating neuro-inflammation and functional recovery was investigated after ischemic cerebral damage. To this end, the rat model of transient middle cerebral artery occlusion (tMCAO) was constructed, the cell model of oxygen-glucose deprivation (OGD) was established using BV2 microglial cells, and the aberrant expression of ALMS1-IT1 was assessed in brain tissues. After ALMS1-IT1 knockdown through intrathecal injection of Lv-shALMS1-IT1, neuro-inflammatory response and functional tests including a modified neurological severity score (mNSS) and a foot-fault test were assessed. Results: The level of ALMS1-IT1 was promptly enhanced at 12 hours (h) following MCAO, peaking at 48 h, and remaining high at day 14 compared to the sham group. Pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) were increased after MCAO, whereas ALMS1-IT1 inhibition suppressed the expression of IL-1β, IL-6 and TNF-α in MCAO rats. The results from mNSS and foot-fault test showed that ALMS1-IT1 knockdown significantly improved spatial learning and sensorimotor function of MCAO rats. Mechanistically, ALMS1-IT1 knockdown suppressed the activation of NF-κB signaling in vitro and in vivo, as evidenced by decreased p65 expression and p65 nuclear translocation. ALMS1-IT1 overexpression facilitated pro-inflammatory cytokines expression in microglia, whereas the effect was blocked by treatment with JSH-23 (a specific NF-κB inhibitor). Conclusions: These data demonstrated that ALMS1-IT1 inhibition improved neurological function of MCAO rats, at least in part by repressing NF-κB-dependent neuro-inflammation.

scholarly journals Sphingosin-1-phosphate Receptor 1: a Potential Target to Inhibit Neuroinflammation and Restore the Sphingosin-1-phosphate Metabolism

2015 ◽  
Vol 42 (3) ◽  
pp. 195-202 ◽  
Author(s):  
Zeynab Kolahdooz ◽  
Sanaz Nasoohi ◽  
Masoumeh Asle-Rousta ◽  
Abolhassan Ahmadiani ◽  
Leila Dargahi
Keyword(s):  
Expression Profile ◽  
Memory Deficit ◽  
Metabolizing Enzymes ◽  
Potential Target ◽  
Tnf Α ◽  
Sphingosine 1 Phosphate ◽  
Inflammatory Processes ◽  
Anti Inflammatory ◽  
Neuro Inflammation

AbstractBackground: Recent evidence suggests that an extreme shift may occur in sphingosine metabolism in neuroinflammatory contexts. Sphingosine 1-phosphate (S1P)-metabolizing enzymes (SMEs) regulate the level of S1P. We recently found that FTY720, a S1P analogue, and SEW2871, a selective S1P receptor 1 (S1P1) agonist, provide protection against neural damage and memory deficit in amyloid beta (Aβ)-injected animals. This study aimed to evaluate the effects of these two analogues on the expression of SMEs as well as their anti-inflammatory roles. Methods: Rats were treated with intracerebral lipopolysaccharide (LPS) or Aβ. Memory impairment was assessed by Morris water maze and the effects of drugs on SMEs as well as inflammatory markers, TNF- α and COX-II, were determined by immunoblotting. Results: Aβ and LPS differentially altered the expression profile of SMEs. In Aβ-injected animals, FTY720 and SEW2871 treatments exerted anti-inflammatory effects and restored the expression profile of SMEs, in parallel to our previous findings. In LPS animals however, in spite of anti-inflammatory effects of the two analogues, only FTY720 restored the levels of SMEs and prevented memory deficit. Conclusion: The observed ameliorating effects of FTY720 and SEW7821 can be partly attributed to the interruption of the vicious cycle of abnormal S1P metabolism and neuro-inflammation. The close imitation of the FTY720 effects by SW2871 in Aβ-induced neuro-inflammation may highlight the attractive role of S1P1 as a potential target to restore S1P metabolism and inhibit inflammatory processes.

scholarly journals Cytokines and Onchocerciasis-Associated Epilepsy, a Pilot Study and Review of the Literature

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 310
Author(s):  
Melissa Krizia Vieri ◽  
An Hotterbeekx ◽  
Stephen Raimon ◽  
Gasim Abd-Elfarag ◽  
Deby Mukendi ◽  
...  
Keyword(s):  
Pilot Study ◽  
Neurological Disorders ◽  
Democratic Republic ◽  
Review Of The Literature ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Republic Of The Congo ◽  
Neurological Conditions ◽  
Neuro Inflammation ◽  
A Prospective Study

Neuro-inflammation may be associated with onchocerciasis-associated epilepsy (OAE) but thus far very few immunological studies have been performed in children with this form of epilepsy. In a pilot study we measured the cytokine levels in cerebrospinal fluid (CSF) of persons with OAE from Maridi, South Sudan, and from Mosango, Democratic Republic of the Congo (DRC) and compared these results with cytokine levels in CSF of Africans with non-OAE neurological disorders, and Europeans with epilepsy or other neurological conditions. The following cytokines were studied: IL-6, TNF-α, IL1-β, IL-5, IL-4, IL-13, CCL3 (Mip-1α), VEGF-C, VCAM-1. No cytokine was significantly associated with OAE, although a lower IL-13 level was observed in CSF of persons with OAE compared to African controls. Observed cytokine profiles and neuro-inflammation may be the consequence of long-standing epilepsy, concomitant infections and malnutrition. Ideally cytokine levels should be determined in a prospective study in serum and CSF collected at the time of onset of the first seizures.

scholarly journals Formyl Peptide Receptor (FPR)1 Modulation by Resveratrol in an LPS-Induced Neuroinflammatory Animal Model

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1418
Author(s):  
Rosa Calvello ◽  
Antonia Cianciulli ◽  
Chiara Porro ◽  
Piergianni Moda ◽  
Francesco De Nuccio ◽  
...  
Keyword(s):  
Murine Model ◽  
Inflammatory Responses ◽  
Sirtuin 1 ◽  
Formyl Peptide Receptor ◽  
Proinflammatory Mediators ◽  
Tnf Α ◽  
Formyl Peptide ◽  
Anti Inflammatory ◽  
Neuro Inflammation ◽  
Sirt1 Gene

Among therapeutic approaches that have been investigated, targeting of receptors implicated in managing neuroinflammation has been described. One such family of receptors comprises the formyl peptide receptors (FPRs) whose ligands could play a role in host defense. The murine FPR gene family includes at least six members while in humans there are only three. The two most important members are the Fpr1 and Fpr2. Fpr1encodes murine FPR1, which is considered the murine orthologue of human FPR. Resveratrol, a non-flavonoid polyphenol rich in red wine and grapes, apart from its beneficial health effects and anti-inflammatory properties, has been reported to reduce neuroinflammation in different neurodegenerative disease models. Resveratrol anti-inflammatory responses involve the activation of the protein deacetylase sirtuin 1 (SIRT1) gene. In this work we have investigated in an LPS-based murine model of neuroinflammation the role of FPR1, examining not only if this receptor undergoes a reduction of its expression during neuroinflammation, but also whether treatment with resveratrol was able to modulate its expression leading to an amelioration of neuroinflammatory picture in a murine model of neuroinflammation. Results of this work showed that FPR1 together with SIRT1 resulted upregulated by resveratrol treatment and that this increase is associated with an amelioration of the neuroinflammatory picture, as demonstrated by the induction of IL-10 and IL1-RA expression and the downregulation of proinflammatory mediators, such as TNF-α and IL-1β. The expression and the modulation of FPR1 by resveratrol may be evaluated in order to propose a novel anti-inflammatory and pro-resolving therapeutic approach for the reduction of the detrimental effects associated with neuro-inflammation based neurodegenerative diseases and also as a promising strategy to promote human health by a diet rich in antioxidative bioactive compounds.

scholarly journals Peripheral inflammatory biomarkers of methamphetamine withdrawal based on the neuro-inflammation hypothesis: the possible improvement effect of exercise

2021 ◽  
Author(s):  
Jingsong Wang ◽  
Chunxia Lu ◽  
Lan Zheng ◽  
Jun Zhang
Keyword(s):  
Resistance Training ◽  
Analogue Scale ◽  
Plasma Concentrations ◽  
Exercise Group ◽  
Control Group ◽  
Peripheral Inflammation ◽  
Elisa Method ◽  
Tnf Α ◽  
Improvement Effect ◽  
Neuro Inflammation

Abstract Background Investigate how exercise affects the desire for methamphetamine (MA) withdrawal and to explore the mechanisms of peripheral inflammation. Methods Ninety methamphetamine withdrawal patients participated enrolled in the study. The subjects were grouped according to the degree of craving induced by the clues: non craving control group (NCC group), craving control group (CC group) and craving exercise group (CE group). The CE group performed aerobic combined resistance training. The ELISA method was then used to detect plasma IL-6, TNF-α and IL-1β concentrations, Visual Analogue Scale(VAS) measurement of cue-induced cravings under Virtual Reality(VR) exposure (VR-VAS) and the Desires for Drug Questionnaire (DDQ) were used to assess cravings. Results Plasma IL-6, TNF-α, IL-1β, levels as well as the VR-VAS and DDQ scores of methamphetamine withdrawal patients were significantly reduced after exercise; The scores of VR-VAS were positively correlated with the plasma concentrations of IL-6, TNF-α and IL-1β. Conclusions This study confirmed that plasma IL-6, TNF-α and IL-1β can be used as biomarkers of peripheral inflammation in methamphetamine withdrawal patients to predict the degree of craving. At the same time,eight weeks of incremental load aerobic combined with resistance training reduces peripheral inflammation, significantly reduces the level of craving for MA extraction.

scholarly journals Autophagy attenuates postoperative cognitive dysfunction by up-regulating cystatin C in aged rats undergoing splenectomy

2019 ◽  
Author(s):  
Bi Xing-hua ◽  
Zhou Long-yuan ◽  
Cai Chang ◽  
Qi Yong ◽  
Yan Li
Keyword(s):  
Learning And Memory ◽  
Cognitive Dysfunction ◽  
Cystatin C ◽  
Postoperative Cognitive Dysfunction ◽  
The Other ◽  
Inflammatory Factors ◽  
Aged Rats ◽  
Tnf Α ◽  
Neuro Inflammation ◽  
Related Proteins

Abstract B ackground : This study aimed to explore whether autophagy can attenuate postoperative cognitive dysfunction (POCD) by up-regulating cystatin C (CysC) in aged rats undergoing splenectomy. Methods : Rats were randomized into four groups ( n = 10 per group): normal control (CON), surgery (SUR), surgery + rapamycin (autophagy inducer) at 1.0 mg/kg/d (RAP), and surgery + 3-methyladenine (autophagy inhibitor) at 3.0 mg/kg/d (3-MA). Treatments were carried out for four weeks. Postoperative learning and memory were assessed using the Morris water maze. Hippocampal expression of the autophagy-related proteins ATG5, LC-3B, Beclin1, and p62 as well as Cys C was assayed using Western blotting and real-time polymerase chain reaction. Results: SUR animals showed higher levels of autophagy and higher expression of autophagy proteins and Cys C than CON animals. These levels were even higher in RAP animals, which also showed lower levels of the inflammatory factors IL-1β, IL-6 and TNF-α than the other groups. Learning and memory functions were higher in RAP animals than in the other groups on days 5 and 7. Effects of 3-MA were opposite to those of RAP. Conclusion : Autophagy improves learning and memory in aged rats following splenectomy, which may involve up-regulation of Cys C and attenuation of neuro-inflammation.

scholarly journals Micro/mini-dystrophines et dystrophie musculaire de Duchenne : entre espoirs et défis

2021 ◽  
pp. 12-17
Author(s):  
Emmanuelle Lagrue ◽  
Claude Cancès ◽  
Juliette Ropars
Keyword(s):  
Essais Cliniques ◽  
Effets Indésirables ◽  
Thérapie Génique ◽  
Modèles Animaux

Les nombreux travaux précliniques de thérapie génique (TG) mis en œuvre afin de modifier l’histoire naturelle de la dystrophie musculaire de Duchenne (DMD), ont aujourd’hui abouti à la mise en place d’essais cliniques évaluant la sécurité et l’efficacité de l’administration de mini- ou micro-dystrophines chez l’enfant, et à terme peut-être chez l’adulte. Nous reprendrons dans cet article le principe général de la TG, les modèles animaux étudiés, les essais cliniques avec mini- ou micro-dystrophine actuellement en cours, et enfin les limites et effets indésirables possibles de ce type de thérapeutique innovante.

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