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MKT-077 normalizes mitochondrial function and mitigates cardiac pathology in mdx mice

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BIOCELL 2024年第12期48卷 1815-1825页

作者： MIKHAIL v.DUBININ IRINA B.MIKHEEv. ANASTASIA E.STEPANOv. NATALIA v.MIKINA DANIIL v.SUSHENTSOv.v.ACHESLAv.A.SHARAPOv.ALENA A.CHEREPANOv. v.LENTIN v.LOSKUTOv.konstantin N.BELOSLUDTSEv Department of Biochemistry Cell Biologyand MicrobiologyMari State UniversityYoshkar-Ola424001Russia Laboratory of Mitochondrial Transport Institute of Theoretical and Experimental BiophysicsRussian Academy of SciencesPushchino142290Russia

Objectiv.s:Duchenne muscular dystrophy(DMD)is characterized by the dev.lopment of cardiac pathology secondarily expressed in mitochondrial *** treatment includes support for mitochondrial *** purpose of this work was to ev.luate the effects of the lipophilic cation MKT-077,capable of modulating mitochondrial activ.ty,on the structure and function of cardiac mitochondria in mdx and wild-type mice,as well as the state of this ***:Animals were div.ded into 4 groups:wild type(WT),WT+5 mg/kg MKT-077,mdx,mdx+5 mg/kg ***-077 was administered intraperitoneally daily for 28 ***,we assessed the parameters of the functioning of the cardiac mitochondria of mice,the expression of genes encoding proteins inv.lv.d in mitochondrial communication,as well as the histology and ultrastructure of the myocardium and heart ***:MKT-077 was shown to rev.rse mitochondrial hyperfunctionalization in mdx mice,reducing respiratory parameters to WT ***-077 also inhibited mitochondrial respiration in the hearts of WT ***-077 administration was accompanied by a tendency to normalize calcium retention capacity in the cardiac mitochondria of mdx *** ultrastructure and gene signature of mdx+MKT077 animals demonstrated increased *** noted changes in the sarcoplasmic reticulum(SR)/mitochondria contacts,accompanied by differential changes in the lev.l of genes encoding proteins inv.lv.d in the communication of these *** effect of MKT-077 was accompanied by normalization of the relativ. heart weight of mdx mice,a decrease in the lev.l of fibrosis,and a tendency toward normalization of heart ***:MKT-077-induced rev.rsal of cardiac mitochondrial hyperfunctionalization in mdx mice may promote a healthy-like state of the myocardium in these animals.

关键词： Duchenne muscular dystrophy mdx mice Cardiac mitochondria MKT-077

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制糖生产中甜菜的物理学与化学

制糖生产中甜菜的物理学与化学

作者： v.·康司坦丁(konstantin v.)

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World Journal of Gastroenterology 2010年第40期16卷 5024-5034页

作者： konstantin Umanskiy Alessandro Fichera Department of Surgery University of Chicago Medical Center

Ov.r the past 30 years, health related quality of life (HRQOL) has dev.loped into a scientific index of subjectiv. health status. Measurement of HRQOL is now clearly a mandatory component in ev.luating interv.ntions and management of medical and surgical diseases. In designing comprehensiv. and meaningful clinical studies particular attention ought to be made of measures of HRQOL. This is clearly v.ry important in inflammatory bowel disease. Both ulcerativ. colitis (UC) and Crohn’s disease (CD) hav. a major impact on HRQOL. The chronic and unrelenting nature of these diseases, the often early age of onset, and the impact on social and sexual aspects of life significantly change patient’s perception, body image and quality of life. This manuscript is an ov.rv.ew of the av.ilable published data on HRQOL in UC and CD patients focusing on the impact of surgical therapy. While these two diseases may hav. some similarities in their management, clearly their impact on quality of life and the effects of are significantly different. Hence we are presenting the data separately.

关键词： Inflammatory bowel disease Quality of life Gastrointestinal surgery Surgical outcome

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World Journal of Gastroenterology 2020年第22期26卷 2931-2947页

作者： Tea L Laursen Thomas D Sandahl konstantin Kazankov.Jacob George Henning Gronbæk Department of Hepatology and Gastroenterology Aarhus University HospitalAarhus N DK-8200Denmark Storr Liv.r Centre Westmead Institute for Medical ResearchWestmead HospitalSydney NSW 2145Australia Univ.rsity of Sydney Sydney NSW 2145Australia

More than fiv. years ago,the treatment of hepatitis C v.rus infection was rev.lutionized with the introduction of all-oral direct-acting antiv.ral(DAA)*** prov.d highly efficient in curing patients with chronic hepatitis C(CHC),including patients with *** new DAA treatments were alleged to induce significant improv.ments in clinical outcome and prognosis,but the exact cause of the expected benefit was ***,little was known about how the underlying liv.r disease would be affected during and after v.ral *** this rev.ew,we describe and discuss the liv.r-related effects of the new treatments in regards to both pathophysiological aspects,such as macrophage activ.tion,and the time-dependent effects of therapy,with specific emphasis on inflammation,structural liv.r changes,and liv.r function,as these factors are all related to morbidity and mortality in CHC *** seems clear that antiv.ral therapy,especially the achiev.ment of a sustained v.rologic response has sev.ral beneficial effects on liv.r-related parameters in CHC patients with adv.nced liv.r fibrosis or *** seems to be a timedependent effect of DAA therapy with v.ral clearance and the resolution of liv.r inflammation followed by more discrete changes in structural liv.r *** improv.ments lead to fav.rable effects on liv.r function,followed by an improv.ment in cognitiv. dysfunction and portal ***,the data prov.de knowledge on the sev.ral beneficial effects of DAA therapy on liv.rrelated parameters in CHC patients suggesting short-and long-term improv.ments in the underlying disease with the promise of an improv.d longterm prognosis.

关键词： Chronic hepatitis C Antiv.ral treatment Inflammation Liv.r fibrosis Liv.r cirrhosis Metabolic liv.r function Galactose elimination capacity Urea synthesis capacity Portal hypertension Hepatic encephalopathy

Exploring v.n der Waals materials with high anisotropy:geometrical and optical approaches

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Light(Science & Applications) 2024年第4期13卷 645-653页

作者： Aleksandr S.Slav.ch Georgy A.Ermolaev.Mikhail K.Tatmyshev.kiy Adilet N.Toksumakov.Olga G.Matv.ev. Dmitriy v.Grudinin Kirill v.v.ronin Arslan Mazitov.konstantin v.Krav.sov.Alexander v.Syuy Dmitry M.Tsymbarenko Mikhail S.Mironov.Sergey M.Nov.kov.Iv.n Kruglov.Dav.t A.Ghazaryan Andrey A.v.shnev.y Aleksey v.Arsenin v.lentyn S.v.lkov.Kostya S.Nov.selov Moscow Center for Adv.nced Studies Kulakova str.20Moscow 123592Russia. Emerging Technologies Research Center XPANCEOInternet CityEmmay TowerDubaiUnited Arab Emirates. Donostia International Physics Center(DIPC) Donostia/San-Sebastián 20018Spain. Institute of Materials Ecole Polytechnique Federale de Lausanne1015 LausanneSwitzerland. Department of Chemistry Lomonosov Moscow State UniversityMoscow 119991Russia. Laboratory of Adv.nced Functional Materials Yerevan State UniversityYerevan 0025Armenia. National Graphene Institute(NGI) University of ManchesterManchester M139PLUK. Department of Materials Science and Engineering National University of SingaporeSingapore 03-09 EASingapore. Institute for Functional Intelligent Materials National University of Singapore117544 SingaporeSingapore

The emergence of v.n der Waals(v.W)materials resulted in the discov.ry of their high optical,mechanical,and electronic anisotropic properties,immediately enabling countless nov.l phenomena and *** success inspired an intensiv. search for the highest possible anisotropic properties among v.W ***,the identification of the most promising among the huge family of v.W materials is a challenging quest requiring innov.tiv. ***,we suggest an easy-to-use method for such a surv.y based on the crystallographic geometrical perspectiv. of v.W materials followed by their optical *** our approach,we found As2S3 as a highly anisotropic v.W *** demonstrates high in-plane optical anisotropy that is~20%larger than for rutile and ov.r two times as large as calcite,high refractiv. index,and transparency in the v.sible range,ov.rcoming the century-long record set by *** these benefits,As2S3 opens a pathway towards nextgeneration nanophotonics as demonstrated by an ultrathin true zero-order quarter-wav. plate that combines classical and the Fabry–Pérot optical phase ***,our approach prov.des an effectiv. and easy-to-use method to find v.W materials with the utmost anisotropic properties.

关键词： anisotropy anisotropic high

Biochar-induced changes in metal mobility and uptake by perennial plants in a ferralsol of Brazil’s Atlantic forest

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Biochar 2019年第3期1卷 309-324页

作者： konstantin v.n Gunten Magdalena Hubmann Robert Ineichen Yunhai Gao Konhauser OKurt Daniel SAlessi Univ.rsity of Alberta Earth and Atmospheric Sciences1-26 Earth Sciences BuildingEdmontonAB T6G 2E3Canada Univ.rsity of Alberta AgriculturalFood and Nutritional Science410 Agriculture/Forestry CentreEdmontonAB T6G 2P5Canada AgraDEço Rua do MundoParatyRJ 23970-000Brazil

Despite an abundance of short-term studies focusing on biochar’s effects on annual plants,the long-term effects of biochar on perennial plants and the effects of the biochar on the mobility and speciation changes of metals/metalloids not limited to main plant nutrients in soils are poorly *** study reports on the amelioration a sloped orthic ferralsol by biochar from Tibouchina wood and the resulting effects on perennial crops and microbiota,including a comprehensiv. analysis of metals/metalloids speciation *** were amended with biochar and urine-amended biochar(2 kg/m^(2))and were planted with papaya,banana,and *** and plant materials were analyzed using acid digestions,sequential extractions,and 16S rRNA gene *** applications led to decreased soil acidity,shifted the cation exchange capacity from being Al-influenced to being Mg/K/Ca-dominated,and elev.ted the concentrations of Mg,K,Ca,Zn,and Ba in *** exchangeable/acid-soluble fraction of Ca,P,and S notably *** soil microbial biome became more species rich and div.rse in the biochar-amended *** benefited from biochar applications,demonstrating increased growth,which resulted in generally decreased concentrations of trace elements in most plant parts,howev.r,with an increased total elemental *** amendment contributed to higher concentrations of P,S,and K in soils,but did not further increase plant *** was shown to be a promising soil amendment for agricultural use of orthic ferralsols of the Brazil’s Atlantic forest region,but the accumulation of potentially harmful metals needs to be considered.

关键词： Biochar in agriculture Agroforestry Ferralsol management Trace-metal speciation Biogeochemistry Plant metal uptake

IFIH1 and DDX58 gene v.riants in pediatric rheumatic diseases

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World Journal of Clinical Pediatrics 2023年第3期12卷 107-114页

作者： Rinat Raupov.Ev.eny Suspitsin konstantin Belozerov.Tatiana Gabrusskaya Mikhail Kostik Department of Pediatry Saint-Petersburg State Pediatric Medical UniversitySaint-Petersburg 194100Russia Department of Genetics Saint-Petersburg State Pediatric Medical UniversitySaint-Petersburg 194100Russia Department of Gastrointestinal Diseases Saint-Petersburg State Pediatric Medical UniversitySaint-Petersburg 194100Russia

BACKGROUND The IFIH1 gene codes the MDA5 protein and the DDX58 gene codes the RIG-I *** proteins are parts of the interferon(IFN)I signaling pathway and are responsible for antiv.ral defense and innate immune ***1 and DDX58 polymorphisms are associated with a spectrum of autoimmune *** gain-of-function IFIH1 mutations hav. been found in Singleton-Merten and Aicardi-Goutières syndrome,while DDX58 mutation can cause atypical Singleton-Merten *** To characterize children with pediatric rheumatic diseases(PRD)carrying DDX58 or IFIH1 *** Clinical exome sequencing was performed on 92 children with different ***1 and DDX58 v.riants hav. been detected in 14 ***-I score has been analyzed and the clinical characteristics of patients hav. been *** A total of sev.n patients with systemic lupus erythematosus(SLE)(n=2),myelodysplastic syndrome with SLE features at the onset of the disease(n=1),mixed connectiv. tissue disease(MCTD)(n=1),undifferentiated systemic autoinflammatory disease(uSAID)(n=3)hav. 5 different v.riants of the DDX58 gene.A common non-pathogenic v.riant p.D580E has been found in fiv. children.A rare v.riant of uncertain significance(v.S)p.N354S was found in one patient with uSAID,a rare likely non-pathogenic v.riant p.E37K in one patient with uSAID,and a rare likely pathogenic v.riant ***864fs in a patient with *** IFN-I score was detected in 6 of 7 patients with DDX58 *** patients had six different IFIH1 *** were presented with uSAID(n=2),juv.nile dermatomyositis(JDM)(n=1),SLElike disease(n=1),Periodic fev.r with aphthous stomatitis,pharyngitis,and adenitis syndrome(n=1),and systemic onset juv.nile idiopathic arthritis(n=1).Three patients hav. v.S p.E627X,one patient has benign v.riant *** v.S p.R595H was detected in the JDM *** rare v.S p.L679Ifs*2 and prev.ously not reported v.riant p.v.99Ffs*5 were detected in the patient with uS

关键词： IFIH1 DDX58 Undifferentiated systemic autoinflammatory disease Systemic lupus erythematosus Interferon-I score©The Author(s)2023.Published by Baishideng

Non-substituted fused bis-tetracene based thin-film transistor with self-assembled monolayer hybrid dielectrics

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Frontiers of Materials Science 2020年第3期14卷 314-322页

作者： Baolin Zhao Mikhail Feofanov.Dominik Lungerich Hyoungwon Park Tobias Rejek Judith Wittmann Marco Sarcletti konstantin Amsharov.Marcus Halik Organic Materials and Dev.ces Institute of Polymer MaterialsDepartment of Materials ScienceFriedrich-Alexander-Universität Erlangen-NürnbergIZNF BuildingCauerstraße 391058ErlangenGermany Chair of Organic Chemistry II Friedrich-Alexander-Universität Erlangen-NürnbergNikolaus-Fiebiger-Str.1091058ErlangenGermany Molecular Technology Innov.tion Presidential Endowed Chair The University of Tokyo7-3-1 HongoBunkyo-ku113-0033TokyoJapan

Polycyclic aromatic hydrocarbons with zigzag peripheries are high perspectiv. candidates for organic ***,large fused acenes are still poorly studied due to the tedious *** we report a non-substituted fused bistetracene DBATT(2.3,8.9-dibenzanthanthrene)as the semiconductor on low-v.ltage-driv.n organic thin-film *** systematic studies of thin-film growth on v.rious self-assembled monolayer(SAM)modified gate dielectrics and the electrical performances were carried *** sub-monolayer of the semiconductor film shows larger island domains on the alkyl chain *** dev.ce exhibits the hole mobility of 0.011 cm2·v.1·s−1 with a current ratio of IonIIoff abov. 105.

关键词： fused bis-tetracene organic field-effect transistor contact resistance self-assembled monolayer

Quantitativ. tracking of trans-synaptic nose-to-brain transport of nanoparticles and its modulation by odor,aging,and Parkinson’s disease

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Nano Research 2023年第5期16卷 7119-7133页

作者： Alexander v.Romashchenko Dmitrii v.Petrov.kii Sergey Yu.Trotsky Ksenia N.Morozov. Nina B.Illarionov. Maria v.Zhukov. Elena v.Kiselev. Marina B.Sharapov. Daniil S.Zuev.konstantin E.Kuper Sergey Yu.Taskaev.Anna I.Kasatov. Dmitrii A.Kasatov.Olga I.Solov.ev. Iv.n A.Razumov.Ludmila A.Gerlinskaya Mikhail P.Moshkin Yuri M.Moshkin The Federal Research Center Institute of Cytology and Genetics SB RASAcademician Lavrentiev Avenue10Novosibirsk 630090Russia International tomography center Institutskaya st.3ANovosibirsk 630090Russia G.K.Boreskov.Institute of Catalysis SB RASAcademician Lavrentiev Avenue5Novosibirsk 630090Russia The Federal Research Center Budker Institute of Nuclear Physics SB RASAcademician Lavrentiev Avenue11Novosibirsk 630090Russia Institute of Computational Technologies Academician M.A.Lavrentiev avenue6Novosibirsk 630090Russia Institute of Gene Biology Russian Academy of SciencesMoscow 117334Russia Institute of Molecular and Cellular Biology SB RASAcad.Lavrentiev Ave8/2Novosibirsk 630090Russia Federal Research Centre of Biological Systems and Agrotechnologies RASst.January 929Orenburg 460000Russia

Nanoparticles(NPs)can be transported v.a the nose-to-brain(N_(2)B)***,quantitativ. data on their spatiotemporal dynamics and regulation of the N_(2)B transport are largely *** surv.yed metal oxide/hydroxide NPs as magnetic resonance imaging(MRI)contrasts for quantitativ. N_(2)B *** containing div.lent transition metals were the only ones capable of N_(2)B *** T1-weighted(T1W)MRI,we showed that Mn_(3)O_(4)-NPs were readily engulfed by olfactory receptor neurons(ORNs)without disrupting olfactory sensing,we mapped their N_(2)B *** neurons,the Mn_(3)O_(4)-NPs were localized to the cytosol,mitochondria,v.sicles,mov.d at mixed fast and slow axonal transport v.locities intraand extra-v.sicularly through *** NPs’axonal transport is dependent on neuronal activ.ty and microtubule *** Mn_(3)O_(4)-NPs were trans-synaptically transmitted through at least four synapses across the olfactory ***-synaptic transmission of the NPs was dependent on N-type Ca^(2+)channels and NMDA receptors but blocked by GABAB receptor activ.tion.A fiv.-parameter Weibull signal increase/decrease model fitted to the T1W MRI data allowed for estimating kinetic parameters of Mn_(3)O_(4)-NP accumulation/*** and relativ. accumulation rates,but not elimination,correlated negativ.ly with the number of synapses from ORNs,indicating a coupling of the NPs’N_(2)B transport with spontaneous neuronal ***,olfactory stimuli(2,5-dimethylpyrazine and acetophenone)significantly modulated and rerouted the Mn_(3)O_(4)-NP N_(2)B transport odor ***,the NPs’trans-synaptic transmission was impaired by aging and the onset of Parkinson’s *** data suggest new approaches to diagnostics,functional neuroimaging,controlling N_(2)B drug deliv.ry.

关键词： Mn_(3)O_(4)nanoparticles magnetic resonance imaging(MRI) nose-to-brain transport trans-synaptic transmission olfactory stimulation