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Additive neurorestorative effects of exercise and docosahexaenoic acid intake in a mouse model of Parkinson’s disease

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Neural Regeneration Research 2025年第2期20卷 574-586页

作者： Olivier Kerdiles Méryl-Farelle Oye Mintsa Mi-mba Katherine Coulombe Cyntia Tremblay VincentÉmond Martine Saint-Pierre Clémence Rouxel Line Berthiaume Pierre Julien Francesca Cicchetti Frédéric Calon Facultéde pharmacie UniversitéLaval1050 Avenue de la MédecineQuebecQCCanada Axe Neuroscience Centre de recherche du CHU de Québec-UniversitéLaval(Pavillon CHUL)2705 Boulevard LaurierQuebecQCCanada institute of Nutrition and Functional Foods QuebecQCCanada Optinutribrain International Associated Laboratory(NutriNeuro FranceINAFCanada)QuebecQCCanada Axe Endocrinologie et Néphrologie Centre de recherche du CHU de Québec-UniversitéLavalQuebecQCCanada Département de Médecine Facultéde MédecineUniversitéLavalQuebecQCCanada Département de Psychiatrie et Neurosciences Facultéde MédecineQuebecQCCanada

There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after *** that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic ***,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal *** weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 *** this period,the animals had access to a running wheel,which they could use or *** acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars ***,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned *** to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned *** present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.

关键词： 6-hydroxydopamine dopamine dopamine transporter exercise neurorestoration Parkinson’s disease polyunsaturated fatty acids omega-3

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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn J.W.So Konstantin Feinberg Marina Manoraj Jenny Cheung Jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research institute Neuroscience and Mental Health ProgramTorontoONCanada institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

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Bioactivity of mackerel peptides on obesity and insulin resistance,an in-vivo study

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Food Bioscience 2022年第3期47卷 394-402页

作者： Soheila Abachi Hokmabadinazhad Jean-Philippe Songpadith Vanessa P.Houde Geneviève Pilon Ismail Fliss André Marette Laurent Bazinet Lucie Beaulieu institute of Nutrition and Functional Foods (INAF) Université LavalQuebecQuebecCanada Department of Food Science Faculty of Agricultural and Food SciencesUniversité LavalQuebecQuebecCanada Department of Medicine Faculty of MedicineCardiology Axis of the Quebec Heart and Lung InstituteQuebecQuebecCanada

Of many metabolic irregularity risk factors,glucose intolerance,insulin resistance,and abdominal obesity are the main *** risk of vascular diseases and cancers is rather high in such individuals therefore its treatment and prevention are equally important for the health of *** including fish biopeptides have frequently shown to prevent and or ameliorate these risk *** our earlier studies,Atlantic mackerel hydrolysate and its fractions showed promising effects on immunity and ***,therefore,in the current study,aimed to examine the effects of mackerel hydrolysate along its cationic peptides,isolated at pH3 using electrodialysis with ultrafiltration membrane,on metabolic disorder factors in diet-induced insulin resistant obese *** were fed the chow and or the hypercaloric diet (high fat high sucrose) for the duration of *** the hypercaloric fed insulin resistant obese mice were gavaged daily either the vehicle and or the test material at the dosage of 208 mg of sample protein per kg mice body *** to our observations,mackerel peptides could not effectively modulate food intake,weight gain,adiposity,plasma glucose and insulin concentrations,hepatic cholesterol,and triglyceride ***,obesity and metabolic impairments could not be averted by the treatments in insulin resistant obese *** conclusion,anti-hypertensive,and immunomodulatory attributes of mackerel peptides at the tested concentrations do not seem to be correlated with its metabolic syndrome benefiting *** presume a general statement about the metabolic syndrome benefiting potency of Atlantic mackerel's biopeptides further research is warranted.

关键词： Atlantic mackerel Bioactivity Cationic peptides Diabetes Obesity

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Investigation on removal pathways of Di 2-ethyl hexyl phthalate from synthetic municipal wastewater using a submerged membrane bioreactor

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Journal of Environmental Sciences 2015年第11期27卷 37-50页

作者： Mehdi Zolfaghari Patrick Drogui Brahima Seyhi Satinder Kaur Brar Gerardo Buelna Rino Dubé Nouha Klai National institute of Scientific Research Water Earth and Environment (INRS-ETE) University of Quebec Industrial Research Center of quebec

Highly hydrophobic Di 2-ethyl hexyl phthalate（DEHP） is one of the most prevalent plasticizers in wastewaters. Since its half-life in biological treatment is around 25 days, it can be used as an efficiency indicator of wastewater treatment plant for the removal of hydrophobic emerging contaminants. In this study, the performance of submerged membrane bioreactor was monitored to understand the effect of DEHP on the growth of aerobic microorganisms. The data showed that the chemical oxygen demand（COD）and ammonia concentration were detected below 10 and 1.0 mg/L, respectively for operating conditions of hydraulic retention time（HRT） = 4 and 6 hr, sludge retention time（SRT） = 140 day and sludge concentration between 11.5 and 15.8 g volatile solid（VS）/L. The removal efficiency of DEHP under these conditions was higher and ranged between 91% and 98%. Results also showed that the removal efficiency of DEHP in biological treatment depended on the concentration of sludge, as adsorption is the main mechanism of its removal. For the submerged membrane bioreactor, the pore size is the pivotal factor for DEHP removal, since it determines the amount of soluble microbial products coming out of the process. Highly assimilated microorganisms increase the biodegradation rate, as 74% of inlet DEHP was biodegraded; however, the concentration of DEHP inside sludge was beyond the discharge limit. Understanding the fate of DEHP in membrane bioreactor,which is one of the most promising and futuristic treatment process could provide replacement for conventional processes to satisfy the future stricter regulations on emerging contaminants.

关键词： Di 2-ethyl hexyl phthalate Submerged membrane bioreactor Removal efficiency Soluble microbial products Toxicity

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Human mitochondrial DNA diseases and Drosophila models

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Journal of Genetics and Genomics 2019年第4期46卷 201-212页

作者： Zhe Chen Fan Zhang Hong Xu National heart Lung and Blood InstituteNational Institute of Health

Mutations that disrupt the mitochondrial genome cause a number of human diseases whose phenotypic presentation varies widely among tissues and individuals. This variability owes in part to the unconventional genetics of mitochondrial DNA(mtDNA), which includes polyploidy, maternal inheritance and dependence on nuclear-encoded factors. The recent development of genetic tools for manipulating mitochondrial genome in Drosophila melanogaster renders this powerful model organism an attractive alternative to mammalian systems for understanding mtDNA-related diseases. In this review, we summarize mtDNA genetics and human mtDNA-related diseases. We highlight existing Drosophila models of mtDNA mutations and discuss their potential use in advancing our knowledge of mitochondrial biology and in modeling human mitochondrial disorders. We also discuss the potential and present challenges of gene therapy for the future treatment of mtDNA diseases.

关键词： Mitochondrial DNA mtDNA disease mtDNA genetics Drosophila model

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Infliximab does not increase colonic cancer risk associated to murine chronic colitis

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World Journal of Gastroenterology 2016年第44期22卷 9727-9733页

作者： Loris R Lopetuso Valentina Petito Tiziano Zinicola Cristina Graziani Viviana Gerardi Vincenzo Arena Maria Emiliana Caristo Andrea Poscia Giovanni Cammarota Alfredo Papa Valerio Cufino Alessandro Sgambato Antonio Gasbarrini Franco Scaldaferri Gastroenterology Division Catholic University of Sacred Heart institute of Pathology Catholic University of Sacred Heart Experimental Center Catholic University of Sacred Heart institute of Hygiene Catholic University of Sacred Heart institute of General Pathology Catholic University of Sacred Heart

AIM To explore the influence of Infliximab(IFX) on cancer progression in a murine model of colonic cancer associated to chronic *** AOM/DSS model was induced in C57BL/6 mice. Mice were injected with IFX(5 mg/kg) during each DSS cycle while control mice received saline. Body weight, occult blood test and stool consistency were measured to calculate the disease activity index(DAI). Mice were sacrificed at week 10 and colons were analyzed macroscopically and microscopically for number of cancers and degree of inflammation. MTT assay was performed on CT26 to evaluate the potential IFX role on metabolic activity and proliferation. Cells were incubated with TNF-α or IFX or TNF-α plus IFX, and cell vitality was evaluated after 6, 24 and 48 h. The same setting was used after pre-incubation with TNF-α for 24 *** IFX significantly reduced DAI and body weight loss in mice compared with controls, preserving also colon length at sacrifice. Histological score was also reduced in treated mice. At macroscopic analysis, IFX treated mice showed a lower number of tumor lesions compared to controls. This was confirmed at microscopic analysis, although differences were not statistically significant. In vitro, IFX treated CT26 maintained similar proliferation ability at MTT test, both when exposed to IFX alone and when associated to TNF-α.CONCLUSION IFX did not increase colonic cancer risk in AOM-DSS model of cancer on chronic colitis nor influence directly the proliferation of murine colon cancer epithelial cells.

关键词： Inflammatory bowel disease Ulcerative colitis Colorectal cancer Infliximab AOM-DSS model Cancer on chronic colitis

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Post-infarct cardiac injury, protection and repair:roles of non-cardiomyocyte multicellular and acellular components

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Science China(Life Sciences) 2018年第3期61卷 266-276页

作者： Xiaojun Du Experimental Cardiology Laboratory Baker Heart and Diabetes Institute

Following myocardial infarction(MI), cardiomyocytes and infarct size are the focus of our attention when evaluating the extent of cardiac injury, efficacy of therapies or success in repairing the damaged heart by stem cell therapy. Numerous interventions have been shown by pre-clinical studies to be effective in limiting infarct size, and yet clinical trials designed accordingly have yielded disappointing outcomes. The ultimate goal of cardiac protection is to limit the adverse cardiac remodeling. Accumulating studies have revealed that post-infarct remodeling can be attenuated without infarct size limitation. To reconcile this, one needs to appreciate the significance of various cellular and acellular myocardial components that, like cardiomyocytes, undergo significant damage and dysfunction, which impact the ultimate cardiac injury and remodelling. Microvascular injury following ischemia-reperfusion may influence infarct size and promote inflammation. Myocardial injury evokes innate immunity with massive inflammatory infiltration that, although essential for the healing process, exacerbates myocardial injury and damage to extracellular matrix leading to dilative remodeling. It is also important to consider the multiple non-cardiomyocyte components in evaluating therapeutic efficacy. Current research indicates the pivotal role of these components in achieving cardiac regeneration by cell therapy. This review summarizes findings in this field, highlights a broad consideration of therapeutic targets,and recommends cardiac remodeling as the ultimate target.

关键词： myocardial infarction ventricular remodelling infarct size inflammation extracellular matrix microvascular damage autonomic nerves

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Immersible ergocycle prescription as a function of relative exercise intensity

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Journal of Sport and Health Science 2017年第2期6卷 219-224页

作者： Mauricio Garzon Mathieu Gayda Anil Nigam Alain-Steve Comtois Martin Juneau Cardiovascular Prevention and Rehabilitation Centre (EPIC) Montreal Heart Institute and University of Montreal Montreal Quebec HIT 1N6 Canada Research Center Montreal Heart Institute and University of Montreal Montreal Quebec H1T 1C8 Canada Department of Kinesiology University of Monireal Montreal Quebec H3T 1J4 Canada Department of Medicine University of Montreal Montreal Quebec H3T 1J4 Canada Kinanthropology Department University of Quebec in Montreal (UQAM) Montreal Quebec H2X 1Y4 Canada

Purpose: The purpose of this study was to establish the relationship between various expressions of relative exercise intensity percentage of maximal oxygen uptake(%VO_(2max)), percentage of maximal heart rate(%HR_(max)), %VO_2 reserve(%VO_2R), and %HR reserve(%HRR)) in order to obtain the more appropriate method for exercise intensity prescription when using an immersible ergocycle(IE) and to propose a prediction equation to estimate oxygen consumption(VO_2) based on IE pedaling rate(rpm) for an individualized exercise training ***: Thirty-three healthy participants performed incremental exercise tests on IE and dryland ergocycle(DE) at equal external power output(Pext). Exercise on IE began at 40 rpm and was increased by 10 rpm until exhaustion. Exercise on DE began with an initial load of 25 W and increased by 25 W/min until exhaustion. VO_2 was measured with a portable gas analyzer(COSMED K4b^2) during both incremental tests. On IE and DE, %VO_2R, %HRmax, and %HRR at equal Pext did not differ(p > 0.05).Results: The %HRR vs. %VO_2R regression for both IE and DE did not differ from the identity line %VO_2R IE = 0.99 × HRR IE(%) + 0.01(r^2= 0.91, SEE = 11%); %VO_2R DE = 0.94 × HRR DE(%) + 0.01(r^2= 0.94, SEE = 8%). Similar mean values for %HRmax, %VO_2R, and %HRR at equal Pext were observed on IE and DE. Predicted VO_2 obtained according to rpm on IE is represented by: VO_2(L/min) = 0.000542 × rpm2-0.026 × rpm + 0.739(r = 0.91, SEE = 0.319 L/min).Conclusion: The %HRR–%VO_2R relationship appears to be the most accurate for exercise training prescription on IE. This study offers new tools to better prescribe, control, and individualize exercise intensity on IE.

关键词： Exercise prescription heart rate Immersed ergocycle Oxygen uptake Pedaling rate

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Neocuspidization of the Pulmonary Valve with Autologous Pericardium in the Adult Patient with Ventricular Septal Defect and Infective Endocarditis: A Case Report and Review of the Literature

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Congenital heart Disease 2022年第6期17卷 641-646页

作者： Igor Mokryk Vitaly Demyanchuk Volodymyr Vashkeba Ilya Nechay Borys Todurov Department of Adult Cardiac Surgery Heart InstituteKyivUkraine Department of Pediatric Cardiac Surgery Heart InstituteKyivUkraine

Congenital heart disease (CHD) is one of the risk factors for developing infective endocarditis (IE). Right-sided IEoccurs in 5%–10% of endocarditis cases, and pulmonary valve (PV) is involved in less than 2% of such *** data are few, and optimal treatment methods, indications for surgery, and types of operative techniquesare still under debate. We present an adult patient with a rare combination of the ventricular septal defect (VSD)and PV IE who underwent surgical treatment. Neocuspidization with autologous pericardium was utilized for thereconstruction of his PV. We discuss details of this novel surgical technique.

关键词： Infective endocarditis pulmonary valve neocuspidization ozaki technique congenital heart disease

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The role of sex chromosomes in mammalian germ cell differentiation： can the germ cells carrying X and Y chromosomes differentiate into fertile oocytes？

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Asian Journal of Andrology 2015年第3期17卷 360-366页

作者： Teruko Taketo Department of Surgery Research Institute of MUHC McGill University Montreal Quebec Canada Department of Biology McGill University Montreal Quebec Canada Department of Obstetrics and Gynecology McGill University Montreal Quebec Canada

The sexual differentiation of germ cells into spermatozoa or oocytes is strictly regulated by their gonadal environment, testis or ovary, which is determined by the presence or absence of the Y chromosome, respectively. Hence, in normal mammalian development, male germ cells differentiate in the presence of X and Y chromosomes, and female germ cells do so in the presence of two X chromosomes. However, gonadal sex reversal occurs in humans as well as in other mammalian species, and the resultant XX males and XY females can lead healthy lives, except for a complete or partial loss of fertility. Germ cells carrying an abnormal set of sex chromosomes are efficiently eliminated by multilayered surveillance mechanisms in the testis, and also, though more variably, in the ovary. Studying the molecular basis for sex-specific responses to a set of sex chromosomes during gametogenesis will promote our understanding of meiotic processes contributing to the evolution of sex determining mechanisms. This review discusses the fate of germ cells carrying various sex chromosomal compositions in mouse models, the limitation of which may be overcome by recent successes in the differentiation of functional germ cells from embryonic stem cells under experimental conditions.

关键词： embryonic stem cells germ cells oocyte sex chromosomes sex reversal

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