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<option value="acoustics"> Acoustics </option>
<option value="amh"> Acta Microbiologica Hellenica (AMH) </option>
<option value="actuators"> Actuators </option>
<option value="admsci"> Administrative Sciences </option>
<option value="adolescents"> Adolescents </option>
<option value="arm"> Advances in Respiratory Medicine (ARM) </option>
<option value="aerobiology"> Aerobiology </option>
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<option value="agriengineering"> AgriEngineering </option>
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<option value="agronomy"> Agronomy </option>
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<option value="applbiosci"> Applied Biosciences </option>
<option value="applmech"> Applied Mechanics </option>
<option value="applmicrobiol"> Applied Microbiology </option>
<option value="applnano"> Applied Nano </option>
<option value="applsci"> Applied Sciences </option>
<option value="asi"> Applied System Innovation (ASI) </option>
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<option value="appliedmath"> AppliedMath </option>
<option value="aquacj"> Aquaculture Journal </option>
<option value="architecture"> Architecture </option>
<option value="arthropoda"> Arthropoda </option>
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<option value="automation"> Automation </option>
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<option value="behavsci"> Behavioral Sciences </option>
<option value="beverages"> Beverages </option>
<option value="BDCC"> Big Data and Cognitive Computing (BDCC) </option>
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<option value="biologics"> Biologics </option>
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<option value="biomedicines"> Biomedicines </option>
<option value="biomedinformatics"> BioMedInformatics </option>
<option value="biomimetics"> Biomimetics </option>
<option value="biomolecules"> Biomolecules </option>
<option value="biophysica"> Biophysica </option>
<option value="biosensors"> Biosensors </option>
<option value="biotech"> BioTech </option>
<option value="birds"> Birds </option>
<option value="blockchains"> Blockchains </option>
<option value="brainsci"> Brain Sciences </option>
<option value="buildings"> Buildings </option>
<option value="businesses"> Businesses </option>
<option value="carbon"> C </option>
<option value="cancers"> Cancers </option>
<option value="cardiogenetics"> Cardiogenetics </option>
<option value="catalysts"> Catalysts </option>
<option value="cells"> Cells </option>
<option value="ceramics"> Ceramics </option>
<option value="challenges"> Challenges </option>
<option value="ChemEngineering"> ChemEngineering </option>
<option value="chemistry"> Chemistry </option>
<option value="chemproc"> Chemistry Proceedings </option>
<option value="chemosensors"> Chemosensors </option>
<option value="children"> Children </option>
<option value="chips"> Chips </option>
<option value="civileng"> CivilEng </option>
<option value="cleantechnol"> Clean Technologies (Clean Technol.) </option>
<option value="climate"> Climate </option>
<option value="ctn"> Clinical and Translational Neuroscience (CTN) </option>
<option value="clinpract"> Clinics and Practice </option>
<option value="clockssleep"> Clocks & Sleep </option>
<option value="coasts"> Coasts </option>
<option value="coatings"> Coatings </option>
<option value="colloids"> Colloids and Interfaces </option>
<option value="colorants"> Colorants </option>
<option value="commodities"> Commodities </option>
<option value="complications"> Complications </option>
<option value="compounds"> Compounds </option>
<option value="computation"> Computation </option>
<option value="csmf"> Computer Sciences & Mathematics Forum </option>
<option value="computers"> Computers </option>
<option value="condensedmatter"> Condensed Matter </option>
<option value="conservation"> Conservation </option>
<option value="constrmater"> Construction Materials </option>
<option value="cmd"> Corrosion and Materials Degradation (CMD) </option>
<option value="cosmetics"> Cosmetics </option>
<option value="covid"> COVID </option>
<option value="crops"> Crops </option>
<option value="cryo"> Cryo </option>
<option value="cryptography"> Cryptography </option>
<option value="crystals"> Crystals </option>
<option value="cimb"> Current Issues in Molecular Biology (CIMB) </option>
<option value="curroncol"> Current Oncology </option>
<option value="dairy"> Dairy </option>
<option value="data"> Data </option>
<option value="dentistry"> Dentistry Journal </option>
<option value="dermato"> Dermato </option>
<option value="dermatopathology"> Dermatopathology </option>
<option value="designs"> Designs </option>
<option value="diabetology"> Diabetology </option>
<option value="diagnostics"> Diagnostics </option>
<option value="dietetics"> Dietetics </option>
<option value="digital"> Digital </option>
<option value="disabilities"> Disabilities </option>
<option value="diseases"> Diseases </option>
<option value="diversity"> Diversity </option>
<option value="dna"> DNA </option>
<option value="drones"> Drones </option>
<option value="ddc"> Drugs and Drug Candidates (DDC) </option>
<option value="dynamics"> Dynamics </option>
<option value="earth"> Earth </option>
<option value="ecologies"> Ecologies </option>
<option value="econometrics"> Econometrics </option>
<option value="economies"> Economies </option>
<option value="education"> Education Sciences </option>
<option value="electricity"> Electricity </option>
<option value="electrochem"> Electrochem </option>
<option value="electronicmat"> Electronic Materials </option>
<option value="electronics"> Electronics </option>
<option value="ecm"> Emergency Care and Medicine </option>
<option value="encyclopedia"> Encyclopedia </option>
<option value="endocrines"> Endocrines </option>
<option value="energies"> Energies </option>
<option value="esa"> Energy Storage and Applications (ESA) </option>
<option value="eng"> Eng </option>
<option value="engproc"> Engineering Proceedings </option>
<option value="entropy"> Entropy </option>
<option value="environsciproc"> Environmental Sciences Proceedings </option>
<option value="environments"> Environments </option>
<option value="epidemiologia"> Epidemiologia </option>
<option value="epigenomes"> Epigenomes </option>
<option value="ebj"> European Burn Journal (EBJ) </option>
<option value="ejihpe"> European Journal of Investigation in Health, Psychology and Education (EJIHPE) </option>
<option value="fermentation"> Fermentation </option>
<option value="fibers"> Fibers </option>
<option value="fintech"> FinTech </option>
<option value="fire"> Fire </option>
<option value="fishes"> Fishes </option>
<option value="fluids"> Fluids </option>
<option value="foods"> Foods </option>
<option value="forecasting"> Forecasting </option>
<option value="forensicsci"> Forensic Sciences </option>
<option value="forests"> Forests </option>
<option value="fossstud"> Fossil Studies </option>
<option value="foundations"> Foundations </option>
<option value="fractalfract"> Fractal and Fractional (Fractal Fract) </option>
<option value="fuels"> Fuels </option>
<option value="future"> Future </option>
<option value="futureinternet"> Future Internet </option>
<option value="futurepharmacol"> Future Pharmacology </option>
<option value="futuretransp"> Future Transportation </option>
<option value="galaxies"> Galaxies </option>
<option value="games"> Games </option>
<option value="gases"> Gases </option>
<option value="gastroent"> Gastroenterology Insights </option>
<option value="gastrointestdisord"> Gastrointestinal Disorders </option>
<option value="gastronomy"> Gastronomy </option>
<option value="gels"> Gels </option>
<option value="genealogy"> Genealogy </option>
<option value="genes"> Genes </option>
<option value="geographies"> Geographies </option>
<option value="geohazards"> GeoHazards </option>
<option value="geomatics"> Geomatics </option>
<option value="geometry"> Geometry </option>
<option value="geosciences"> Geosciences </option>
<option value="geotechnics"> Geotechnics </option>
<option value="geriatrics"> Geriatrics </option>
<option value="glacies"> Glacies </option>
<option value="gucdd"> Gout, Urate, and Crystal Deposition Disease (GUCDD) </option>
<option value="grasses"> Grasses </option>
<option value="hardware"> Hardware </option>
<option value="healthcare"> Healthcare </option>
<option value="hearts"> Hearts </option>
<option value="hemato"> Hemato </option>
<option value="hematolrep"> Hematology Reports </option>
<option value="heritage"> Heritage </option>
<option value="histories"> Histories </option>
<option value="horticulturae"> Horticulturae </option>
<option value="hospitals"> Hospitals </option>
<option value="humanities"> Humanities </option>
<option value="humans"> Humans </option>
<option value="hydrobiology"> Hydrobiology </option>
<option value="hydrogen"> Hydrogen </option>
<option value="hydrology"> Hydrology </option>
<option value="hygiene"> Hygiene </option>
<option value="immuno"> Immuno </option>
<option value="idr"> Infectious Disease Reports </option>
<option value="informatics"> Informatics </option>
<option value="information"> Information </option>
<option value="infrastructures"> Infrastructures </option>
<option value="inorganics"> Inorganics </option>
<option value="insects"> Insects </option>
<option value="instruments"> Instruments </option>
<option value="iic"> Intelligent Infrastructure and Construction </option>
<option value="ijerph"> International Journal of Environmental Research and Public Health (IJERPH) </option>
<option value="ijfs"> International Journal of Financial Studies (IJFS) </option>
<option value="ijms" selected="selected"> International Journal of Molecular Sciences (IJMS) </option>
<option value="IJNS"> International Journal of Neonatal Screening (IJNS) </option>
<option value="ijpb"> International Journal of Plant Biology (IJPB) </option>
<option value="ijt"> International Journal of Topology </option>
<option value="ijtm"> International Journal of Translational Medicine (IJTM) </option>
<option value="ijtpp"> International Journal of Turbomachinery, Propulsion and Power (IJTPP) </option>
<option value="ime"> International Medical Education (IME) </option>
<option value="inventions"> Inventions </option>
<option value="IoT"> IoT </option>
<option value="ijgi"> ISPRS International Journal of Geo-Information (IJGI) </option>
<option value="J"> J </option>
<option value="jal"> Journal of Ageing and Longevity (JAL) </option>
<option value="jcdd"> Journal of Cardiovascular Development and Disease (JCDD) </option>
<option value="jcto"> Journal of Clinical & Translational Ophthalmology (JCTO) </option>
<option value="jcm"> Journal of Clinical Medicine (JCM) </option>
<option value="jcs"> Journal of Composites Science (J. Compos. Sci.) </option>
<option value="jcp"> Journal of Cybersecurity and Privacy (JCP) </option>
<option value="jdad"> Journal of Dementia and Alzheimer's Disease (JDAD) </option>
<option value="jdb"> Journal of Developmental Biology (JDB) </option>
<option value="jeta"> Journal of Experimental and Theoretical Analyses (JETA) </option>
<option value="jfb"> Journal of Functional Biomaterials (JFB) </option>
<option value="jfmk"> Journal of Functional Morphology and Kinesiology (JFMK) </option>
<option value="jof"> Journal of Fungi (JoF) </option>
<option value="jimaging"> Journal of Imaging (J. Imaging) </option>
<option value="jintelligence"> Journal of Intelligence (J. Intell.) </option>
<option value="jlpea"> Journal of Low Power Electronics and Applications (JLPEA) </option>
<option value="jmmp"> Journal of Manufacturing and Materials Processing (JMMP) </option>
<option value="jmse"> Journal of Marine Science and Engineering (JMSE) </option>
<option value="jmahp"> Journal of Market Access & Health Policy (JMAHP) </option>
<option value="jmp"> Journal of Molecular Pathology (JMP) </option>
<option value="jnt"> Journal of Nanotheranostics (JNT) </option>
<option value="jne"> Journal of Nuclear Engineering (JNE) </option>
<option value="ohbm"> Journal of Otorhinolaryngology, Hearing and Balance Medicine (JOHBM) </option>
<option value="jpm"> Journal of Personalized Medicine (JPM) </option>
<option value="jpbi"> Journal of Pharmaceutical and BioTech Industry (JPBI) </option>
<option value="jor"> Journal of Respiration (JoR) </option>
<option value="jrfm"> Journal of Risk and Financial Management (JRFM) </option>
<option value="jsan"> Journal of Sensor and Actuator Networks (JSAN) </option>
<option value="joma"> Journal of the Oman Medical Association (JOMA) </option>
<option value="jtaer"> Journal of Theoretical and Applied Electronic Commerce Research (JTAER) </option>
<option value="jvd"> Journal of Vascular Diseases (JVD) </option>
<option value="jox"> Journal of Xenobiotics (JoX) </option>
<option value="jzbg"> Journal of Zoological and Botanical Gardens (JZBG) </option>
<option value="journalmedia"> Journalism and Media </option>
<option value="kidneydial"> Kidney and Dialysis </option>
<option value="kinasesphosphatases"> Kinases and Phosphatases </option>
<option value="knowledge"> Knowledge </option>
<option value="labmed"> LabMed </option>
<option value="laboratories"> Laboratories </option>
<option value="land"> Land </option>
<option value="languages"> Languages </option>
<option value="laws"> Laws </option>
<option value="life"> Life </option>
<option value="limnolrev"> Limnological Review </option>
<option value="lipidology"> Lipidology </option>
<option value="liquids"> Liquids </option>
<option value="literature"> Literature </option>
<option value="livers"> Livers </option>
<option value="logics"> Logics </option>
<option value="logistics"> Logistics </option>
<option value="lubricants"> Lubricants </option>
<option value="lymphatics"> Lymphatics </option>
<option value="make"> Machine Learning and Knowledge Extraction (MAKE) </option>
<option value="machines"> Machines </option>
<option value="macromol"> Macromol </option>
<option value="magnetism"> Magnetism </option>
<option value="magnetochemistry"> Magnetochemistry </option>
<option value="marinedrugs"> Marine Drugs </option>
<option value="materials"> Materials </option>
<option value="materproc"> Materials Proceedings </option>
<option value="mca"> Mathematical and Computational Applications (MCA) </option>
<option value="mathematics"> Mathematics </option>
<option value="medsci"> Medical Sciences </option>
<option value="msf"> Medical Sciences Forum </option>
<option value="medicina"> Medicina </option>
<option value="medicines"> Medicines </option>
<option value="membranes"> Membranes </option>
<option value="merits"> Merits </option>
<option value="metabolites"> Metabolites </option>
<option value="metals"> Metals </option>
<option value="meteorology"> Meteorology </option>
<option value="methane"> Methane </option>
<option value="mps"> Methods and Protocols (MPs) </option>
<option value="metrics"> Metrics </option>
<option value="metrology"> Metrology </option>
<option value="micro"> Micro </option>
<option value="microbiolres"> Microbiology Research </option>
<option value="micromachines"> Micromachines </option>
<option value="microorganisms"> Microorganisms </option>
<option value="microplastics"> Microplastics </option>
<option value="minerals"> Minerals </option>
<option value="mining"> Mining </option>
<option value="modelling"> Modelling </option>
<option value="molbank"> Molbank </option>
<option value="molecules"> Molecules </option>
<option value="mti"> Multimodal Technologies and Interaction (MTI) </option>
<option value="muscles"> Muscles </option>
<option value="nanoenergyadv"> Nanoenergy Advances </option>
<option value="nanomanufacturing"> Nanomanufacturing </option>
<option value="nanomaterials"> Nanomaterials </option>
<option value="ndt"> NDT </option>
<option value="network"> Network </option>
<option value="neuroglia"> Neuroglia </option>
<option value="neurolint"> Neurology International </option>
<option value="neurosci"> NeuroSci </option>
<option value="nitrogen"> Nitrogen </option>
<option value="ncrna"> Non-Coding RNA (ncRNA) </option>
<option value="nursrep"> Nursing Reports </option>
<option value="nutraceuticals"> Nutraceuticals </option>
<option value="nutrients"> Nutrients </option>
<option value="obesities"> Obesities </option>
<option value="oceans"> Oceans </option>
<option value="onco"> Onco </option>
<option value="optics"> Optics </option>
<option value="oral"> Oral </option>
<option value="organics"> Organics </option>
<option value="organoids"> Organoids </option>
<option value="osteology"> Osteology </option>
<option value="oxygen"> Oxygen </option>
<option value="parasitologia"> Parasitologia </option>
<option value="particles"> Particles </option>
<option value="pathogens"> Pathogens </option>
<option value="pathophysiology"> Pathophysiology </option>
<option value="pediatrrep"> Pediatric Reports </option>
<option value="pets"> Pets </option>
<option value="pharmaceuticals"> Pharmaceuticals </option>
<option value="pharmaceutics"> Pharmaceutics </option>
<option value="pharmacoepidemiology"> Pharmacoepidemiology </option>
<option value="pharmacy"> Pharmacy </option>
<option value="philosophies"> Philosophies </option>
<option value="photochem"> Photochem </option>
<option value="photonics"> Photonics </option>
<option value="phycology"> Phycology </option>
<option value="physchem"> Physchem </option>
<option value="psf"> Physical Sciences Forum </option>
<option value="physics"> Physics </option>
<option value="physiologia"> Physiologia </option>
<option value="plants"> Plants </option>
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<option value="platforms"> Platforms </option>
<option value="pollutants"> Pollutants </option>
<option value="polymers"> Polymers </option>
<option value="polysaccharides"> Polysaccharides </option>
<option value="populations"> Populations </option>
<option value="poultry"> Poultry </option>
<option value="powders"> Powders </option>
<option value="proceedings"> Proceedings </option>
<option value="processes"> Processes </option>
<option value="prosthesis"> Prosthesis </option>
<option value="proteomes"> Proteomes </option>
<option value="psychiatryint"> Psychiatry International </option>
<option value="psychoactives"> Psychoactives </option>
<option value="psycholint"> Psychology International </option>
<option value="publications"> Publications </option>
<option value="qubs"> Quantum Beam Science (QuBS) </option>
<option value="quantumrep"> Quantum Reports </option>
<option value="quaternary"> Quaternary </option>
<option value="radiation"> Radiation </option>
<option value="reactions"> Reactions </option>
<option value="realestate"> Real Estate </option>
<option value="receptors"> Receptors </option>
<option value="recycling"> Recycling </option>
<option value="rsee"> Regional Science and Environmental Economics (RSEE) </option>
<option value="religions"> Religions </option>
<option value="remotesensing"> Remote Sensing </option>
<option value="reports"> Reports </option>
<option value="reprodmed"> Reproductive Medicine (Reprod. Med.) </option>
<option value="resources"> Resources </option>
<option value="rheumato"> Rheumato </option>
<option value="risks"> Risks </option>
<option value="robotics"> Robotics </option>
<option value="ruminants"> Ruminants </option>
<option value="safety"> Safety </option>
<option value="sci"> Sci </option>
<option value="scipharm"> Scientia Pharmaceutica (Sci. Pharm.) </option>
<option value="sclerosis"> Sclerosis </option>
<option value="seeds"> Seeds </option>
<option value="sensors"> Sensors </option>
<option value="separations"> Separations </option>
<option value="sexes"> Sexes </option>
<option value="signals"> Signals </option>
<option value="sinusitis"> Sinusitis </option>
<option value="smartcities"> Smart Cities </option>
<option value="socsci"> Social Sciences </option>
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<option value="spectroscj"> Spectroscopy Journal </option>
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<option value="epigenomes">Epigenomes</option>
<option value="ebj">European Burn Journal</option>
<option value="ejihpe">European Journal of Investigation in Health, Psychology and Education</option>
<option value="fermentation">Fermentation</option>
<option value="fibers">Fibers</option>
<option value="fintech">FinTech</option>
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<option value="ijerph">International Journal of Environmental Research and Public Health</option>
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<option value="jmmp">Journal of Manufacturing and Materials Processing</option>
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<option value="psychiatryint">Psychiatry International</option>
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<option value="smartcities">Smart Cities</option>
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<option value="siuj">Société Internationale d’Urologie Journal</option>
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<option value="solids">Solids</option>
<option value="spectroscj">Spectroscopy Journal</option>
<option value="sports">Sports</option>
<option value="standards">Standards</option>
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<option value="stresses">Stresses</option>
<option value="surfaces">Surfaces</option>
<option value="surgeries">Surgeries</option>
<option value="std">Surgical Techniques Development</option>
<option value="sustainability">Sustainability</option>
<option value="suschem">Sustainable Chemistry</option>
<option value="symmetry">Symmetry</option>
<option value="synbio">SynBio</option>
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<option value="targets">Targets</option>
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<option value="higheredu">Trends in Higher Education</option>
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<li class=""><label for="ms-opt-189" style="padding-left: 23px;"><input type="checkbox" value="hearts" title="Hearts" id="ms-opt-189">Hearts</label></li>
<li class=""><label for="ms-opt-190" style="padding-left: 23px;"><input type="checkbox" value="hemato" title="Hemato" id="ms-opt-190">Hemato</label></li>
<li class=""><label for="ms-opt-191" style="padding-left: 23px;"><input type="checkbox" value="hematolrep" title="Hematology Reports" id="ms-opt-191">Hematology Reports</label></li>
<li class=""><label for="ms-opt-192" style="padding-left: 23px;"><input type="checkbox" value="heritage" title="Heritage" id="ms-opt-192">Heritage</label></li>
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JOURNAL DESCRIPTION INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES International Journal of Molecular Sciences is an international, peer-reviewed, open access journal providing an advanced forum for biochemistry, molecular and cell biology, molecular biophysics, molecular medicine, and all aspects of molecular research in chemistry, and is published semimonthly online by MDPI. The Australian Society of Plant Scientists (ASPS), Epigenetics Society, European Calcium Society (ECS), European Chitin Society (EUCHIS), Spanish Society for Cell Biology (SEBC) and others are affiliated with IJMS and their members receive a discount on the article processing charges. * Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions. * High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, MEDLINE, Embase, CAPlus / SciFinder, and other databases. * Journal Rank: JCR - Q1 (Biochemistry and Molecular Biology) / CiteScore - Q1 (Inorganic Chemistry) * Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 18.1 days after submission; acceptance to publication is undertaken in 2.8 days (median values for papers published in this journal in the first half of 2024). * Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done. * Testimonials: See what our editors and authors say about the IJMS. * Companion journals for IJMS include: Biophysica, Stresses, Lymphatics and SynBio. Impact Factor: 4.9 (2023); 5-Year Impact Factor: 5.6 (2023) subject Imprint Information get_app Journal Flyer Open Access ISSN: 1422-0067 LATEST ARTICLES 18 pages, 1777 KiB Open AccessArticle Metabolic Syndrome, Inflammation, Oxidative Stress, and Vitamin D Levels in Children and Adolescents with Obesity by Tjaša Hertiš Petek, Evgenija Homšak, Mateja Svetej and Nataša Marčun Varda Int. J. Mol. Sci. 2024, 25(19), 10599; https://doi.org/10.3390/ijms251910599 (registering DOI) - 1 Oct 2024 Abstract Metabolic syndrome (MetS) is associated with systemic inflammation, oxidative stress, and hypovitaminosis D. Our aim was to determine whether vitamin D mediates inflammation and oxidative stress, assessed through selected biomarkers, in children with obesity and/or MetS. Eighty children with normal weight, overweight, or [...] Read more. Metabolic syndrome (MetS) is associated with systemic inflammation, oxidative stress, and hypovitaminosis D. Our aim was to determine whether vitamin D mediates inflammation and oxidative stress, assessed through selected biomarkers, in children with obesity and/or MetS. Eighty children with normal weight, overweight, or obesity were analyzed for serum vitamin D, C-reactive protein, leukocytes, adiponectin, monocyte chemoattractant protein-1, myeloperoxidase, interferon-inducible T-cell alpha chemoattractant (I-TAC/CXCL11), superoxide dismutase-1, fasting lipid and glucose levels, ultrasound-measured abdominal fat thickness, waist circumference, body mass index and blood pressure. Children with obesity or overweight had lower vitamin D levels, increased blood pressure, visceral and subcutaneous fat thickness, and higher leukocytes, C-reactive protein, and myeloperoxidase levels. Those with MetS also had lower adiponectin levels. Vitamin D levels are negatively correlated with body mass index, waist circumference, and visceral and subcutaneous fat thickness. Correlation, mediation, and regression analyses showed no link between vitamin D and inflammatory/oxidative stress variables. The novel biomarker I-TAC did not correlate with obesity or vitamin D status. Our results indicate that vitamin D does not significantly mediate inflammation or oxidative stress in children and adolescents with obesity and/or MetS. Selected inflammation/oxidative stress biomarkers appear to be altered primarily due to obesity rather than vitamin D status. Full article (This article belongs to the Special Issue Metabolic Syndrome: New Insights in Pathogenesis, Diagnosis, Prevention, and Management) attachment Supplementary material: Supplementary File 1 (ZIP, 2185 KiB) 19 pages, 11038 KiB Open AccessArticle YKL40/Integrin β4 Axis Induced by the Interaction between Cancer Cells and Tumor-Associated Macrophages Is Involved in the Progression of High-Grade Serous Ovarian Carcinoma by Keitaro Yamanaka, Yu-ichiro Koma, Satoshi Urakami, Ryosuke Takahashi, Satoshi Nagamata, Masaki Omori, Rikuya Torigoe, Hiroki Yokoo, Takashi Nakanishi, Nobuaki Ishihara, Shuichi Tsukamoto, Takayuki Kodama, Mari Nishio, Manabu Shigeoka, Hiroshi Yokozaki and Yoshito Terai Int. J. Mol. Sci. 2024, 25(19), 10598; https://doi.org/10.3390/ijms251910598 (registering DOI) - 1 Oct 2024 Abstract Macrophages in the tumor microenvironment, termed tumor-associated macrophages (TAMs), promote the progression of various cancer types. However, many mechanisms related to tumor–stromal interactions in epithelial ovarian cancer (EOC) progression remain unclear. High-grade serous ovarian carcinoma (HGSOC) is the most malignant EOC subtype. Herein, [...] Read more. Macrophages in the tumor microenvironment, termed tumor-associated macrophages (TAMs), promote the progression of various cancer types. However, many mechanisms related to tumor–stromal interactions in epithelial ovarian cancer (EOC) progression remain unclear. High-grade serous ovarian carcinoma (HGSOC) is the most malignant EOC subtype. Herein, immunohistochemistry was performed on 65 HGSOC tissue samples, revealing that patients with a higher infiltration of CD68+, CD163+, and CD204+ macrophages had a poorer prognosis. We subsequently established an indirect co-culture system between macrophages and EOC cells, including HGSOC cells. The co-cultured macrophages showed increased expression of the TAM markers CD163 and CD204, and the co-cultured EOC cells exhibited enhanced proliferation, migration, and invasion. Cytokine array analysis revealed higher YKL40 secretion in the indirect co-culture system. The addition of YKL40 increased proliferation, migration, and invasion via extracellular signal-regulated kinase (Erk) signaling in EOC cells. The knockdown of integrin β4, one of the YKL40 receptors, suppressed YKL40-induced proliferation, migration, and invasion, as well as Erk phosphorylation in some EOC cells. Database analysis showed that high-level expression of YKL40 and integrin β4 correlated with a poor prognosis in patients with serous ovarian carcinoma. Therefore, the YKL40/integrin β4 axis may play a role in ovarian cancer progression. Full article (This article belongs to the Special Issue Immunoregulation within the Tumor Microenvironment: Special Emphasis on Macrophages and NK Cells) ►▼ Show Figures Figure 1 Figure 1 attachment Supplementary material: Supplementary File 1 (ZIP, 882 KiB) 19 pages, 1704 KiB Open AccessArticle Readdressing the Localization of Apolipoprotein E (APOE) in Mitochondria-Associated Endoplasmic Reticulum (ER) Membranes (MAMs): An Investigation of the Hepatic Protein–Protein Interactions of APOE with the Mitochondrial Proteins Lon Protease (LONP1), Mitochondrial Import Receptor Subunit TOM40 (TOMM40) and Voltage-Dependent Anion-Selective Channel 1 (VDAC1) by Johanna Rueter, Gerald Rimbach, Stephanie Bilke, Andreas Tholey and Patricia Huebbe Int. J. Mol. Sci. 2024, 25(19), 10597; https://doi.org/10.3390/ijms251910597 (registering DOI) - 1 Oct 2024 Abstract As a component of circulating lipoproteins, APOE binds to cell surface receptors mediating lipoprotein metabolism and cholesterol transport. A growing body of evidence, including the identification of a broad variety of cellular proteins interacting with APOE, suggests additional independent functions. Investigating cellular localization [...] Read more. As a component of circulating lipoproteins, APOE binds to cell surface receptors mediating lipoprotein metabolism and cholesterol transport. A growing body of evidence, including the identification of a broad variety of cellular proteins interacting with APOE, suggests additional independent functions. Investigating cellular localization and protein–protein interactions in cultured human hepatocytes, we aimed to contribute to the elucidation of hitherto unnoted cellular functions of APOE. We observed a strong accumulation of APOE in MAMs, equally evident for the two major isoforms APOE3 and APOE4. Using mass spectrometry proteome analyses, novel and previously noted APOE interactors were identified, including the mitochondrial proteins TOMM40, LONP1 and VDAC1. All three interactors were present in MAM fractions, which we think initially facilitates interactions with APOE. LONP1 is a protease with chaperone activity, which migrated to MAMs in response to ER stress, displaying a reinforced interaction with APOE. We therefore hypothesize that APOE may help in the unfolded protein response (UPR) by acting as a co-chaperone in cooperation with LONP1 at the interface of mitochondria and ER membranes. The interaction of APOE with the integral proteins TOMM40 and VDAC1 may point to the formation of bridging complexes connecting mitochondria with other organelles. Full article (This article belongs to the Special Issue Apolipoproteins and Lipoproteins in Health and Disease, 3rd Edition) ►▼ Show Figures Figure 1 Figure 1 attachment Supplementary material: Supplementary File 1 (ZIP, 65 KiB) 12 pages, 1212 KiB Open AccessReview Polyamines in Dysbiotic Oral Conditions of Older Adults: A Scoping Review by Stephanie Chu, Alice Kit Ying Chan and Chun Hung Chu Int. J. Mol. Sci. 2024, 25(19), 10596; https://doi.org/10.3390/ijms251910596 - 1 Oct 2024 Abstract Polyamines modulate cellular proliferation and function. Their dysregulation results in inflammatory and oncological repercussions. This study aims to map the current literature and provide an overview of polyamines in dysbiotic oral conditions among older adults. English publications indexed in MEDLINE, Scopus, and Web [...] Read more. Polyamines modulate cellular proliferation and function. Their dysregulation results in inflammatory and oncological repercussions. This study aims to map the current literature and provide an overview of polyamines in dysbiotic oral conditions among older adults. English publications indexed in MEDLINE, Scopus, and Web of Science from January 2000 to May 2024 were screened. Eligibility criteria included clinical and laboratory studies using samples from adults aged 65 or above. This scoping review identified 2725 publications and included 19 publications. Ten studies detected that older adults with oral carcinoma had increased levels of polyamines such as spermidine in saliva and tumour-affected tissues. Eight studies reported older adults suffering from periodontal infection had increased levels of polyamines such as putrescine in saliva, gingival crevicular fluid, and biofilm from the gingival crevice. Two studies showed polyamine levels could reflect the success of periodontal therapy. Three studies found older adults with halitosis had increased levels of polyamines such as cadaverine in saliva and tongue biofilm. Polyamines were suggested as biomarkers for these oral conditions. In conclusion, certain polyamine levels are elevated in older adults with oral cancer, periodontal infections, and halitosis. Polyamines may be used as a simple and non-invasive tool to detect dysbiotic oral conditions and monitor treatment progress in older adults (Open Science Framework registration). Full article (This article belongs to the Special Issue Polyamines in Aging and Disease) ►▼ Show Figures Figure 1 Figure 1 19 pages, 915 KiB Open AccessReview Non-Alcoholic Fatty Liver Disease and Coronary Artery Disease: A Bidirectional Association Based on Endothelial Dysfunction by Nikolaos Ktenopoulos, Marios Sagris, Maria Gerogianni, Konstantinos Pamporis, Anastasios Apostolos, Konstantinos Balampanis, Konstantinos Tsioufis, Konstantinos Toutouzas and Dimitris Tousoulis Int. J. Mol. Sci. 2024, 25(19), 10595; https://doi.org/10.3390/ijms251910595 - 1 Oct 2024 Abstract Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is regarded as a liver manifestation of metabolic syndrome. It is linked to insulin resistance, obesity, and diabetes mellitus, all of which increase the risk of cardiovascular complications. [...] Read more. Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is regarded as a liver manifestation of metabolic syndrome. It is linked to insulin resistance, obesity, and diabetes mellitus, all of which increase the risk of cardiovascular complications. Endothelial dysfunction (EnD) constitutes the main driver in the progression of atherosclerosis and coronary artery disease (CAD). Several pathophysiological alterations and molecular mechanisms are involved in the development of EnD in patients with NAFLD. Our aim is to examine the association of NAFLD and CAD with the parallel assessment of EnD, discussing the pathophysiological mechanisms and the genetic background that underpin this relationship. This review delves into the management of the condition, exploring potential clinical implications and available medical treatment options to facilitate the deployment of optimal treatment strategies for these patients. Full article (This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics) ►▼ Show Figures Figure 1 19 pages, 3078 KiB Open AccessArticle GSP1-111 Modulates the Microglial M1/M2 Phenotype by Inhibition of Toll-like Receptor 2: A Potential Therapeutic Strategy for Depression by Ryeong-Eun Kim, Darine Froy Mabunga, Kyung-Jun Boo, Dong Hyun Kim, Seol-Heui Han, Chan Young Shin and Kyoung Ja Kwon Int. J. Mol. Sci. 2024, 25(19), 10594; https://doi.org/10.3390/ijms251910594 - 1 Oct 2024 Abstract Neuroinflammation plays a vital role in neurodegenerative diseases and neuropsychiatric disorders, and microglia and astrocytes chiefly modulate inflammatory responses in the central nervous system (CNS). Toll-like receptors (TLRs), which are expressed in neurons, astrocytes, and microglia in the CNS, are critical for innate [...] Read more. Neuroinflammation plays a vital role in neurodegenerative diseases and neuropsychiatric disorders, and microglia and astrocytes chiefly modulate inflammatory responses in the central nervous system (CNS). Toll-like receptors (TLRs), which are expressed in neurons, astrocytes, and microglia in the CNS, are critical for innate immune responses; microglial TLRs can regulate the activity of these cells, inducing protective or harmful effects on the surrounding cells, including neurons. Therefore, regulating TLRs in microglia may be a potential therapeutic strategy for neurological disorders. We examined the protective effects of GSP1-111, a novel synthetic peptide for inhibiting TLR signaling, on neuroinflammation and depression-like behavior. GSP1-111 decreased TLR2 expression and remarkably reduced the mRNA expression of inflammatory M1-phenotype markers, including tumor necrosis factor (TNF)α, interleukin (IL)-1β, and IL-6, while elevating that of the M2 phenotype markers, Arg-1 and IL-10. In vivo, GSP1-111 administration significantly decreased the depression-like behavior induced by lipopolysaccharide (LPS) in a forced swim test and significantly reduced the brain levels of M1-specific inflammatory cytokines (TNFα, IL-1β, and IL-6). GSP1-111 prevented the LPS-induced microglial activation and TLR2 expression in the brain. Accordingly, GSP1-111 prevented inflammatory responses and induced microglial switching of the inflammatory M1 phenotype to the protective M2 phenotype. Thus, GSP1-111 could prevent depression-like behavior by inhibiting TLR2. Taken together, our results suggest that the TLR2 pathway is a promising therapeutic target for depression, and GSP1-111 could be a novel therapeutic candidate for various neurological disorders. Full article (This article belongs to the Special Issue Roles of Glia in CNS: Toward the Development of New Antidepressant Strategies?) ►▼ Show Figures Graphical abstract Graphical abstract attachment Supplementary material: Supplementary File 1 (ZIP, 259 KiB) 20 pages, 4536 KiB Open AccessArticle Lifespan Extension by Retrotransposons under Conditions of Mild Stress Requires Genes Involved in tRNA Modifications and Nucleotide Metabolism by Patrick H. Maxwell, Mustafa Mahmood, Maya Villanueva, Kaitlyn Devine and Nina Avery Int. J. Mol. Sci. 2024, 25(19), 10593; https://doi.org/10.3390/ijms251910593 - 1 Oct 2024 Abstract Retrotransposons are mobile DNA elements that are more active with increasing age and exacerbate aging phenotypes in multiple species. We previously reported an unexpected extension of chronological lifespan in the yeast, Saccharomyces paradoxus, due to the presence of Ty1 retrotransposons when cells [...] Read more. Retrotransposons are mobile DNA elements that are more active with increasing age and exacerbate aging phenotypes in multiple species. We previously reported an unexpected extension of chronological lifespan in the yeast, Saccharomyces paradoxus, due to the presence of Ty1 retrotransposons when cells were aged under conditions of mild stress. In this study, we tested a subset of genes identified by RNA-seq to be differentially expressed in S. paradoxus strains with a high-copy number of Ty1 retrotransposons compared with a strain with no retrotransposons and additional candidate genes for their contribution to lifespan extension when cells were exposed to a moderate dose of hydroxyurea (HU). Deletion of ADE8, NCS2, or TRM9 prevented lifespan extension, while deletion of CDD1, HAC1, or IRE1 partially prevented lifespan extension. Genes overexpressed in high-copy Ty1 strains did not typically have Ty1 insertions in their promoter regions. We found that silencing genomic copies of Ty1 prevented lifespan extension, while expression of Ty1 from a high-copy plasmid extended lifespan in medium with HU or synthetic medium. These results indicate that cells adapt to expression of retrotransposons by changing gene expression in a manner that can better prepare them to remain healthy under mild stress. Full article (This article belongs to the Special Issue Aging: From Molecular Mechanisms, Pathophysiology to Novel Therapeutic Approaches (2nd Edition)) ►▼ Show Figures Figure 1 Figure 1 attachment Supplementary material: Supplementary File 1 (ZIP, 580 KiB) 13 pages, 1860 KiB Open AccessArticle High BMI Is Associated with Changes in Peritumor Breast Adipose Tissue That Increase the Invasive Activity of Triple-Negative Breast Cancer Cells by Cora E. Miracle, Chelsea L. McCallister, Krista L. Denning, Rebecca Russell, Jennifer Allen, Logan Lawrence, Mary Legenza, Diane Krutzler-Berry and Travis B. Salisbury Int. J. Mol. Sci. 2024, 25(19), 10592; https://doi.org/10.3390/ijms251910592 - 1 Oct 2024 Abstract Breast cancer is the most common cancer in women with multiple risk factors including smoking, genetics, environmental factors, and obesity. Smoking and obesity are the top two risk factors for the development of breast cancer. The effect of obesity on adipose tissue mediates [...] Read more. Breast cancer is the most common cancer in women with multiple risk factors including smoking, genetics, environmental factors, and obesity. Smoking and obesity are the top two risk factors for the development of breast cancer. The effect of obesity on adipose tissue mediates the pathogenesis of breast cancer in the context of obesity. Triple-negative breast cancer (TNBC) is a breast cancer subtype within which the cells lack estrogen, progesterone, and HER2 receptors. TNBC is the deadliest breast cancer subtype. The 5-year survival rates for patients with TNBC are 8–16% lower than the 5-year survival rates for patients with estrogen-receptor-positive breast tumors. In addition, TNBC patients have early relapse rates (3–5 years after diagnosis). Obesity is associated with an increased risk for TNBC, larger TNBC tumors, and increased breast cancer metastasis compared with lean women. Thus, novel therapeutic approaches are warranted to treat TNBC in the context of obesity. In this paper, we show that peritumor breast adipose-derived secretome (ADS) from patients with a high (>30) BMI is a stronger inducer of TNBC cell invasiveness and JAG1 expression than peritumor breast ADS from patients with low (<30) BMI. These findings indicate that patient BMI-associated changes in peritumor AT induce changes in peritumor ADS, which in turn acts on TNBC cells to stimulate JAG1 expression and cancer cell invasiveness. Full article (This article belongs to the Special Issue Mechanism and Role of Adipokines in Cancer) ►▼ Show Figures Figure 1 Figure 1 attachment Supplementary material: Supplementary File 1 (ZIP, 1221 KiB) 16 pages, 3324 KiB Open AccessArticle Polymers Enhance Chlortetracycline Hydrochloride Solubility by Chao Zhang, Bing Li, Yubin Bai, Yangling Liu, Yong Zhang and Jiyu Zhang Int. J. Mol. Sci. 2024, 25(19), 10591; https://doi.org/10.3390/ijms251910591 - 1 Oct 2024 Abstract Chlortetracycline hydrochloride (CTC) is a broad-spectrum tetracycline antibiotic with a wide range of antibacterial activities. Due to low solubility, poor stability, and low bioavailability, clinical preparation development is limited. We sought to improve these solubility and dissolution rates by preparing solid dispersions. A [...] Read more. Chlortetracycline hydrochloride (CTC) is a broad-spectrum tetracycline antibiotic with a wide range of antibacterial activities. Due to low solubility, poor stability, and low bioavailability, clinical preparation development is limited. We sought to improve these solubility and dissolution rates by preparing solid dispersions. A hydrophilic polymer was selected as the carrier, and a solid dispersion was prepared using a medium grinding method, with samples characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FT-IR), and particle size distribution (PSD). To maximize CTC solubility and stability, different polymer types and optimal drug-to-polymer ratios were screened. The solubility of optimized povidone K30 (PVPK30) (1/0.75, w/w)-, hydroxypropyl-β-cyclodextrin (HP-β-CD) (1/2, w/w)-, and gelatin (1/1, w/w)-based solid dispersions was 6.25-, 7.7-, and 3.75-fold higher than that of pure CTC powder, respectively. Additionally, in vitro dissolution studies showed that the gelatin-based solid dispersion had a higher initial dissolution rate. SEM and PS analyses confirmed that this dispersion had smaller and more uniform particles than PVPK30 and HP-β-CD dispersions. Therefore, successful solid polymer dispersion preparations improved the CTC solubility, dissolution rates, and stability, which may have potential as drug delivery systems. Full article (This article belongs to the Section Physical Chemistry and Chemical Physics) ►▼ Show Figures Figure 1 Figure 1 19 pages, 2039 KiB Open AccessArticle Role of Genetic Polymorphisms -238 G>A and -308 G>A, and Serum TNF-α Levels in a Cohort of Mexican Pediatric Neuroblastoma Patients: Preliminary Study by Arturo Ramírez-Pacheco, Silvia Selene Moreno-Guerrero, Luz María Rocha-Ramírez, Gabriela Hernández-Pliego, María Argelia Escobar-Sánchez, Alfonso Reyes-López, Juan José Luis Sienra-Monge and Luis Enrique Juárez-Villegas Int. J. Mol. Sci. 2024, 25(19), 10590; https://doi.org/10.3390/ijms251910590 - 1 Oct 2024 Abstract The results of in vitro and in vivo studies have shown the pro-tumor effects of TNF-α, and this cytokine’s increased expression is associated with poor prognosis in patients with some types of cancer. Our study objective was to evaluate the possible association of [...] Read more. The results of in vitro and in vivo studies have shown the pro-tumor effects of TNF-α, and this cytokine’s increased expression is associated with poor prognosis in patients with some types of cancer. Our study objective was to evaluate the possible association of TNF-α genetic polymorphisms and serum levels with susceptibility and prognosis in a cohort of Mexican patients with NB. We performed PCR-RFLP and ELISA methods to analyze the genetics of these SNPs and determine serum concentrations, respectively. The distribution of the -308 G>A and -238 G>A polymorphisms TNFα genotypes was considerably different between patients with NB and the control group. The SNP rs1800629 GG/GA genotypes were associated with a decreased risk of NB (OR = 0.1, 95% CI = 0.03–0.393, p = 0.001) compared with the AA genotype, which was associated with susceptibility to NB (OR = 2.89, 95% CI = 1.45–5.76, p = 0.003) and related to unfavorable histology and high-risk NB. The rs361525 polymorphism GG genotype was associated with a lower risk of developing NB compared with the GA and AA genotypes (OR = 0.2, 95% CI = 0.068–0.63, p = 0.006). Circulating TNF-α serum concentrations were significantly different (p < 0.001) between patients with NB and healthy controls; however, we found no relationship between the analyzed TNF-α serum levels and SNP genotypes. We found associations between the rs1800629AA genotype and lower event-free survival (p = 0.026); SNP rs361525 and TNF-α levels were not associated with survival in patients with NB. Our results suggest the TNF-α SNP rs1800629 as a probable factor of NB susceptibility. The -308 G/A polymorphism AA genotype has a probable role in promoting NB development and poor prognosis associated with unfavorable histology, high-risk tumors, and lower EFS in Mexican patients with NB. It should be noted that it is important to conduct research on a larger scale, through inter-institutional studies, to further evaluate the contribution of TNF-α genetic polymorphisms to the risk and prognosis of NB. Full article (This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Mexico, 2nd Edition) ►▼ Show Figures Figure 1 Figure 1 attachment Supplementary material: Supplementary File 1 (ZIP, 318 KiB) 15 pages, 4432 KiB Open AccessArticle Genome-Wide Identification, Phylogenetic, and Expression Analysis of Jasmonate ZIM-Domain Gene Family in Medicago Sativa L. by Jing Cui, Xu Jiang, Yajing Li, Lili Zhang, Yangyang Zhang, Xue Wang, Fei He, Mingna Li, Tiejun Zhang and Junmei Kang Int. J. Mol. Sci. 2024, 25(19), 10589; https://doi.org/10.3390/ijms251910589 - 1 Oct 2024 Abstract JASMONATE ZIM domain (JAZ) proteins, inhibitors of the jasmonic acid (JA) signaling pathway, are identified in different plants, such as rice and Arabidopsis. These proteins are crucial for growth, development, and abiotic stress responses. However, limited information is available regarding the JAZ [...] Read more. JASMONATE ZIM domain (JAZ) proteins, inhibitors of the jasmonic acid (JA) signaling pathway, are identified in different plants, such as rice and Arabidopsis. These proteins are crucial for growth, development, and abiotic stress responses. However, limited information is available regarding the JAZ family in alfalfa. This study identified 11 JAZ genes (MsJAZs) in the “Zhongmu No.1” reference genome of alfalfa. The physical and chemical properties, chromosome localization, phylogenetic relationships, gene structure, cis-acting elements, and collinearity of the 11 MsJAZ genes were subsequently analyzed. Tissue-specific analysis revealed distinct functions of different MsJAZ genes in growth and development. The expression patterns of MsJAZ genes under salt stress conditions were validated using qRT-PCR. All MsJAZ genes responded to salt stress, with varying levels of upregulation over time, highlighting their role in stress responses. Furthermore, heterogeneous expression of MsJAZ1 in Arabidopsis resulted in significantly lower seed germination and survival rates in OE-2 and OE-4 compared to the WT under 150 mM NaCl treatment. This study establishes a foundation for further exploration of the function of the JAZ family and provides significant insights into the genetic improvement of alfalfa. Full article (This article belongs to the Section Molecular Genetics and Genomics) ►▼ Show Figures Figure 1 Figure 1 attachment Supplementary material: Supplementary File 1 (ZIP, 708 KiB) 16 pages, 1401 KiB Open AccessArticle Quelling the Geometry Factor Effect in Quantum Chemical Calculations of 13C NMR Chemical Shifts with the Aid of the pecG-n (n = 1, 2) Basis Sets by Yuriy Yu. Rusakov, Valentin A. Semenov and Irina L. Rusakova Int. J. Mol. Sci. 2024, 25(19), 10588; https://doi.org/10.3390/ijms251910588 - 1 Oct 2024 Abstract A root factor for the accuracy of all quantum chemical calculations of nuclear magnetic resonance (NMR) chemical shifts is the quality of the molecular equilibrium geometry used. In turn, this quality depends largely on the basis set employed at the geometry optimization stage. [...] Read more. A root factor for the accuracy of all quantum chemical calculations of nuclear magnetic resonance (NMR) chemical shifts is the quality of the molecular equilibrium geometry used. In turn, this quality depends largely on the basis set employed at the geometry optimization stage. This parameter represents the main subject of the present study, which is a continuation of our recent work, where new pecG-n (n = 1, 2) basis sets for the geometry optimization were introduced. A goal of this study was to compare the performance of our geometry-oriented pecG-n (n = 1, 2) basis sets against the other basis sets in massive calculations of 13C NMR shielding constants/chemical shifts in terms of their efficacy in reducing geometry factor errors. The testing was carried out with both large-sized biologically active natural products and medium-sized compounds with complicated electronic structures. The former were treated using the computation protocol based on the density functional theory (DFT) and considered in the theoretical benchmarking, while the latter were treated using the computational scheme based on the upper-hierarchy coupled cluster (CC) methods and were used in the practical benchmarking involving the comparison with experimental NMR data. Both the theoretical and practical analyses showed that the pecG-1 and pecG-2 basis sets resulted in substantially reduced geometry factor errors in the calculated 13C NMR chemical shifts/shielding constants compared to their commensurate analogs, with the pecG-2 basis set being the best of all the considered basis sets. Full article (This article belongs to the Section Physical Chemistry and Chemical Physics) ►▼ Show Figures Figure 1 Figure 1 attachment Supplementary material: Supplementary File 1 (ZIP, 1921 KiB) 9 pages, 1602 KiB Open AccessCommunication Imaging the Raf–MEK–ERK Signaling Cascade in Living Cells by Young-Chul Shin, Minkyung Cho, Jung Me Hwang, Kyungjae Myung, Hee-Seok Kweon, Zee-Won Lee, Hyun-A. Seong and Kyung-Bok Lee Int. J. Mol. Sci. 2024, 25(19), 10587; https://doi.org/10.3390/ijms251910587 - 1 Oct 2024 Abstract Conventional biochemical methods for studying cellular signaling cascades have relied on destructive cell disruption. In contrast, the live cell imaging of fluorescent-tagged transfected proteins offers a non-invasive approach to understanding signal transduction events. One strategy involves monitoring the phosphorylation-dependent shuttling of a fluorescent-labeled [...] Read more. Conventional biochemical methods for studying cellular signaling cascades have relied on destructive cell disruption. In contrast, the live cell imaging of fluorescent-tagged transfected proteins offers a non-invasive approach to understanding signal transduction events. One strategy involves monitoring the phosphorylation-dependent shuttling of a fluorescent-labeled kinase between the nucleus and cytoplasm using nuclear localization, export signals, or both. In this paper, we introduce a simple method to visualize intracellular signal transduction in live cells by exploring the translocation properties of PKC from the cytoplasm to the membrane. We fused bait protein to PKC, allowing the bait (RFP-labeled) and target (GFP-labeled) proteins to co-translocate from the cytoplasm to the membrane. However, in non-interacting protein pairs, only the bait protein was translocated to the plasma membrane. To verify our approach, we examined the Raf–MEK–ERK signaling cascade (ERK pathway). We successfully visualized direct Raf1/MEK2 interaction and the KSR1-containing ternary complex (Raf1/MEK2/KSR1). However, the interaction between MEK and ERK was dependent on the presence of the KSR1 scaffold protein under our experimental conditions. Full article (This article belongs to the Section Biochemistry) ►▼ Show Figures Figure 1 Figure 1 attachment Supplementary material: Supplementary File 1 (ZIP, 26951 KiB) 12 pages, 860 KiB Open AccessArticle Secondary Metabolites and Their Biological Evaluation from the Aerial Parts of Staehelina uniflosculosa Sibth. & Sm. (Asteraceae) by Maria Lazanaki, George Tsikalas, Olga S. Tsiftsoglou, Haralambos Katerinopoulos, Dimitra Hadjipavlou-Litina and Diamanto Lazari Int. J. Mol. Sci. 2024, 25(19), 10586; https://doi.org/10.3390/ijms251910586 - 1 Oct 2024 Abstract Phytochemical investigation of Staehelina uniflosculosa Sibth. & Sm. resulted in the isolation of twenty-two natural products: eleven sesquiterpene lactones, artemorin (1), tamirin (2), tanachin (3), reynosin (4), baynol C (5), desacetyl-β-cyclopyrethrosin (6 [...] Read more. Phytochemical investigation of Staehelina uniflosculosa Sibth. & Sm. resulted in the isolation of twenty-two natural products: eleven sesquiterpene lactones, artemorin (1), tamirin (2), tanachin (3), reynosin (4), baynol C (5), desacetyl-β-cyclopyrethrosin (6), 1β-hydroxy-4α-methoxy-5α,7α,6β-eudesm-11(13)-en-6,12-olide (7), 1β,4α,6α-trihydroxyeudesm-11-en-8α,12-olide (8), 1β-hydroxy-arbusculin A (9), methyl-1β,4α,6α-trihydroxy-5α,7αH-eudesm-11(13)-en-12-oate (10) and methyl-1β,6α,8α-trihydroxy-5α,7αH-eudesma-4(15),11(13)-dien-12-oate (11); one lignan, pinoresinol (12); one norisoprenoid, loliolide (13); six flavonoids (four genins and two glycosides), hispidulin (14), nepetin (15), jaceosidin (16), eriodictyol (17), eriodictyol-3′-O-β-D-glucoside (18) and eriodictyol-7-O-β-D-glucuronide (19); and three phenolic derivatives (one phenolic acid and two phenolic glucosides), protocatechuic acid (20), arbutin (21) and nebrodenside A (22). From the isolated compounds, only nepetin (15) has been reported previously from the Staehelina genus and, to the best of our knowledge, it is the first time that compound (18) has been identified in Asteraceae. A number of these substances were tested for (a) inhibition of lipoxygenase and acetylocholinesterase, (b) their antioxidant activity using the DPPH (1,1-Diphenyl-2-picrylhydrazyl) method or/and (c) inhibition of lipid peroxidation. The tested components exhibited low antioxidant activity with the exception of 5 and 22, while the effectiveness of these compounds in the inhibition of acetylocholinesterase is limited. Furthermore, Molinspiration, an online computer tool, was used to determine the bioactivity ratings of the isolated secondary metabolites. The compounds’ bioactivity ratings for potential therapeutic targets were very promising. Full article (This article belongs to the Special Issue Molecular Studies of Natural Compounds and Plant Extracts—2nd Edition) ►▼ Show Figures Figure 1 Figure 1 attachment Supplementary material: Supplementary File 1 (ZIP, 590 KiB) 22 pages, 5120 KiB Open AccessArticle Computational Study on the Inhibition Mechanisms of the Ziegler-Natta Catalyst in the Propylene Polymerization Process: Part 1 Effects of Acetylene and Methylacetylene by Joaquin Hernandez-Fernandez, Elias Bello-León and Edgar Marquez Int. J. Mol. Sci. 2024, 25(19), 10585; https://doi.org/10.3390/ijms251910585 - 1 Oct 2024 Abstract Acetylene and methylacetylene are impurities commonly found in the raw materials used for the production of polymers such as polypropylene and polyethylene. Experimental evidence indicates that both acetylene and methylacetylene can decrease the productivity of the Ziegler-Natta catalyst and alter the properties of [...] Read more. Acetylene and methylacetylene are impurities commonly found in the raw materials used for the production of polymers such as polypropylene and polyethylene. Experimental evidence indicates that both acetylene and methylacetylene can decrease the productivity of the Ziegler-Natta catalyst and alter the properties of the resulting polymer. However, there is still a lack of understanding regarding the mechanisms through which these substances affect this process. Therefore, elucidating these mechanisms is crucial to develop effective solutions to this problem. In this study, the inhibition mechanisms of the Ziegler-Natta catalyst by acetylene and methylacetylene are presented and compared with the incorporation of the first propylene monomer (chain initiation) to elucidate experimental effects. The Density Functional Theory (DFT) method was used, along with the B3LYP-D3 functional and the 6-311++G(d,p) basis set. The recorded adsorption energies were −11.10, −13.99, and −0.31 kcal mol−1, while the activation energies were 1.53, 2.83, and 28.36 kcal mol−1 for acetylene, methylacetylene, and propylene, respectively. The determined rate constants were 4.68 × 1011, 5.29 × 1011, and 2.3 × 10−8 M−1 s−1 for acetylene, methylacetylene, and propylene, respectively. Based on these values, it is concluded that inhibition reactions are more feasible than propylene insertion only if an ethylene molecule has not been previously adsorbed, as such an event reinforces propylene adsorption. Full article (This article belongs to the Section Physical Chemistry and Chemical Physics) ►▼ Show Figures Figure 1 Figure 1 15 pages, 2505 KiB Open AccessReview Recombinant Influenza A Viruses Expressing Reporter Genes from the Viral NS Segment by Luis Martinez-Sobrido and Aitor Nogales Int. J. Mol. Sci. 2024, 25(19), 10584; https://doi.org/10.3390/ijms251910584 - 1 Oct 2024 Abstract Studying influenza A viruses (IAVs) requires secondary experimental procedures to detect the presence of the virus in infected cells or animals. The ability to generate recombinant (r)IAV using reverse genetics techniques has allowed investigators to generate viruses expressing foreign genes, including fluorescent and [...] Read more. Studying influenza A viruses (IAVs) requires secondary experimental procedures to detect the presence of the virus in infected cells or animals. The ability to generate recombinant (r)IAV using reverse genetics techniques has allowed investigators to generate viruses expressing foreign genes, including fluorescent and luciferase proteins. These rIAVs expressing reporter genes have allowed for easily tracking viral infections in cultured cells and animal models of infection without the need for secondary approaches, representing an excellent option to study different aspects in the biology of IAV where expression of reporter genes can be used as a readout of viral replication and spread. Likewise, these reporter-expressing rIAVs provide an excellent opportunity for the rapid identification and characterization of prophylactic and/or therapeutic approaches. To date, rIAV expressing reporter genes from different viral segments have been described in the literature. Among those, rIAV expressing reporter genes from the viral NS segment have been shown to represent an excellent option to track IAV infection in vitro and in vivo, eliminating the need for secondary approaches to identify the presence of the virus. Here, we summarize the status on rIAV expressing traceable reporter genes from the viral NS segment and their applications for in vitro and in vivo influenza research. Full article (This article belongs to the Special Issue Bioluminescent and Fluorescent Proteins: Molecular Mechanisms and Modern Applications 4.0) ►▼ Show Figures Figure 1 Figure 1 21 pages, 10738 KiB Open AccessArticle Comparative Analysis of the Cutaneous Microbiome in Psoriasis Patients and Healthy Individuals—Insights into Microbial Dysbiosis: Final Results by Diana Sabina Radaschin, Alina Viorica Iancu, Alexandra Mariana Ionescu, Gabriela Gurau, Elena Niculet, Florin Ciprian Bujoreanu, Cristina Beiu, Alin Laurentiu Tatu and Liliana Gabriela Popa Int. J. Mol. Sci. 2024, 25(19), 10583; https://doi.org/10.3390/ijms251910583 - 1 Oct 2024 Abstract Psoriasis is one of the most frequent chronic inflammatory skin diseases and exerts a significant psychological impact, causing stigmatization, low self-esteem and depression. The pathogenesis of psoriasis is remarkably complex, involving genetic, immune and environmental factors, some of which are still incompletely explored. [...] Read more. Psoriasis is one of the most frequent chronic inflammatory skin diseases and exerts a significant psychological impact, causing stigmatization, low self-esteem and depression. The pathogenesis of psoriasis is remarkably complex, involving genetic, immune and environmental factors, some of which are still incompletely explored. The cutaneous microbiome has become more and more important in the pathogenesis of inflammatory skin diseases such as acne, rosacea, atopic dermatitis and psoriasis. Dysbiosis of the skin microbiome could be linked to acute flare ups in psoriatic disease, as recent studies suggest. Given this hypothesis, we conducted a study in which we evaluated the cutaneous microbiome of psoriasis patients and healthy individuals. In our study, we collected multiple samples using swab sampling, adhesive tape and punch biopsies. Our results are similar to other studies in which the qualitative and quantitative changes found in the cutaneous microbiome of psoriasis patients are different than healthy individuals. Larger, standardized studies are needed in order to elucidate the microbiome changes in psoriasis patients, clarify their role in the pathogenesis of psoriasis, decipher the interactions between the commensal microorganisms of the same and different niches and between microbiomes and the host and identify new therapeutic strategies. Full article (This article belongs to the Special Issue Molecular Research on Skin Disease: From Pathology to Therapy) ►▼ Show Figures Figure 1 Figure 1 15 pages, 2968 KiB Open AccessArticle 3-Alkoxy-1-Benzyl-5-Nitroindazole Derivatives Are Potent Antileishmanial Compounds by Niurka Mollineda-Diogo, Sergio Sifontes-Rodríguez, María Magdalena Aguirre-García, Alma Reyna Escalona-Montaño, Teresa Espinosa-Buitrago, Ricardo Mondragón-Flores, Mónica Edith Mondragón-Castelán, Alfredo Meneses-Marcel, Ofelia Pérez-Olvera, Daniel Andrés Sánchez-Almaraz, Yunierkis Perez-Castillo and Vicente Arán-Redó Int. J. Mol. Sci. 2024, 25(19), 10582; https://doi.org/10.3390/ijms251910582 - 1 Oct 2024 Abstract Indazoles have previously been identified as molecules with antiprotozoal activity. In this study, we evaluate the in vitro activity of thirteen 3-alkoxy-1-benzyl-5-nitroindazole derivatives (series D) against L. amazonensis, L. infantum, and L. mexicana. In vitro, cytotoxicity against mouse peritoneal macrophages and [...] Read more. Indazoles have previously been identified as molecules with antiprotozoal activity. In this study, we evaluate the in vitro activity of thirteen 3-alkoxy-1-benzyl-5-nitroindazole derivatives (series D) against L. amazonensis, L. infantum, and L. mexicana. In vitro, cytotoxicity against mouse peritoneal macrophages and growth inhibitory activity in promastigotes were evaluated for all compounds, and those showing adequate activity and selectivity were tested against intracellular amastigotes. Transmission and scanning electron microscopy were employed to study the effects of 3-alkoxy-1-benzyl-5-nitroindazole and 2-benzyl-5-nitroindazolin-3-one derivatives on promastigotes of L. amazonensis. Compounds NV6 and NV8 were active in the two life stages of the three species, with the latter showing the best indicators of activity and selectivity. 3-alkoxy-1-benzyl-5-nitroindazole derivatives (series D) showed in vitro activity comparable to that of amphotericin B against the promastigote stage of Leishmania spp. Two compounds were also found to be active the amastigote stage. Electron microscopy studies confirmed the antileishmanial activity of the indazole derivatives studied and support future research on this family of compounds as antileishmanial agents. Full article (This article belongs to the Special Issue Advances in Therapeutics against Eukaryotic Pathogens) ►▼ Show Figures Figure 1 Figure 1 attachment Supplementary material: Supplementary File 1 (ZIP, 1603 KiB) 15 pages, 5758 KiB Open AccessArticle Expression Profiling of Coding and Noncoding RNAs in the Endometrium of Patients with Endometriosis by Mi Ran Choi, Hye Jin Chang, Jeong-Hyeon Heo, Sun Hyung Yum, Eunae Jo, Miran Kim and Sang-Rae Lee Int. J. Mol. Sci. 2024, 25(19), 10581; https://doi.org/10.3390/ijms251910581 - 1 Oct 2024 Abstract The aim of this study was to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) in the endometrium of individuals with and without endometriosis (EMS) during the proliferative (P) and secretory (S) phases of the menstrual cycle. Tissues were obtained from 18 control [...] Read more. The aim of this study was to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) in the endometrium of individuals with and without endometriosis (EMS) during the proliferative (P) and secretory (S) phases of the menstrual cycle. Tissues were obtained from 18 control (CT; P-phase [pCT], n = 8; S-phase [sCT], n = 13) and 23 EMS patients (P-phase [pEMS], n = 13; S-phase [sEMS], n = 12). DElncRNAs and DEmRNAs were analyzed using total RNA-sequencing. In P-phase, expression of NONHSAG019742.2 and NONHSAT120701.2 was significantly higher in EMS than control patients, that of while NONHSAG048398.2 and NONHSAG016560.2 was lower in EMS patients. In S-phase, expression of NONHSAT000959.2, NONHSAT203423.1, and NONHSAG053769.2 was significantly increased in EMS patients, while that of NONHSAG012105.2 and NONHSAG020839.2 was lower. In addition, the expression of HSD11B2, THBS1, GPX3, and SHISA6 was similar to that of neighboring lncRNAs in both P- and S-phases. In contrast, ELP3 and NR4A1, respectively, were up- or downregulated in pEMS tissues. In sEMS, expression of LAMB3 and HIF1A was increased, while expression of PAM was reduced. Our findings on lncRNAs and mRNAs encourage not only exploration of the potential clinical applications of lncRNAs and mRNAs as prognostic or diagnostic biomarkers for EMS but also to gain valuable insights into its pathogenesis. Full article (This article belongs to the Special Issue Circulating Non-coding RNAs as Diagnostic and Prognostic Markers of Human Diseases: 2nd Edition) ►▼ Show Figures Figure 1 Figure 1 attachment Supplementary material: Supplementary File 1 (ZIP, 1429 KiB) 20 pages, 12174 KiB Open AccessArticle Multisite Injections of Canine Glial-Restricted Progenitors Promote Brain Myelination and Extend the Survival of Dysmyelinated Mice by Piotr Rogujski, Magdalena Gewartowska, Michal Fiedorowicz, Malgorzata Frontczak-Baniewicz, Joanna Sanford, Piotr Walczak, Miroslaw Janowski, Barbara Lukomska and Luiza Stanaszek Int. J. Mol. Sci. 2024, 25(19), 10580; https://doi.org/10.3390/ijms251910580 - 1 Oct 2024 Abstract Glial cell dysfunction results in myelin loss and leads to subsequent motor and cognitive deficits throughout the demyelinating disease course.Therefore, in various therapeutic approaches, significant attention has been directed toward glial-restricted progenitor (GRP) transplantation for myelin repair and remyelination, and numerous studies using [...] Read more. Glial cell dysfunction results in myelin loss and leads to subsequent motor and cognitive deficits throughout the demyelinating disease course.Therefore, in various therapeutic approaches, significant attention has been directed toward glial-restricted progenitor (GRP) transplantation for myelin repair and remyelination, and numerous studies using exogenous GRP injection in rodent models of hypomyelinating diseases have been performed. Previously, we proposed the transplantation of canine glial-restricted progenitors (cGRPs) into the double-mutant immunodeficient, demyelinated neonatal shiverer mice (shiverer/Rag2−/−). The results of our previous study revealed the myelination of axons within the corpus callosum of transplanted animals; however, the extent of myelination and lifespan prolongation depended on the transplantation site (anterior vs. posterior). The goal of our present study was to optimize the therapeutic effect of cGRP transplantation by using a multisite injection protocol to achieve a broader dispersal of donor cells in the host and obtain better therapeutic results. Experimental analysis of cGRP graft recipients revealed a marked elevation in myelin basic protein (MBP) expression and prominent axonal myelination across the brains of shiverer mice. Interestingly, the proportion of galactosyl ceramidase (GalC) positive cells was similar between the brains of cGRP recipients and control mice, implying a natural propensity of exogenous cGRPs to generate mature, myelinating oligodendrocytes. Moreover, multisite injection of cGRPs improved mice survival as compared to non-transplanted animals. Full article (This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics) ►▼ Show Figures Figure 1 Figure 1 More Articles... 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Int. J. Mol. Sci. 2024, 25(17), 9551; https://doi.org/10.3390/ijms25179551 Published: 3 September 2024 Review The Role of Molecular and Cellular Aging Pathways on Age-Related Hearing Loss by Tuba Ege et al. Int. J. Mol. Sci. 2024, 25(17), 9705; https://doi.org/10.3390/ijms25179705 Published: 7 September 2024 Review Development of mRNA Lipid Nanoparticles: Targeting and Therapeutic Aspects by Yaping Liu et al. Int. J. Mol. Sci. 2024, 25(18), 10166; https://doi.org/10.3390/ijms251810166 Published: 22 September 2024 Review Circular RNAs: Novel Players in Cancer Mechanisms and Therapeutic Strategies by Jimi Kim Int. J. Mol. Sci. 2024, 25(18), 10121; https://doi.org/10.3390/ijms251810121 Published: 20 September 2024 Review The Pathophysiological Mechanism and Clinical Treatment of Polycystic Ovary Syndrome: A Molecular and Cellular Review of the Literature by Kai-Jung Chang et al. Int. J. Mol. 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