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From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

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Neural Regeneration Research 2025年第3期20卷 660-670页

作者： Ernesto Doncel-pérez Gabriel Guízar-Sahagún Israel Grijalva-Otero Hospital Nacional de parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical Research Unit for Neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoratio

关键词： neural regeneration neuroprotection spinal cord injury repair spinal cord injury treatments structural restoration of spinal cord injury

Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural Regeneration Research 2025年第3期20卷 725-739页

作者： Benjamin R.Helmold Angela Ahrens Zachary Fitzgerald p.Hande Ozdinler Department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of Medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： ALS2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions SpAST spastin

LIVE IMAGING OF EARLY DEVELOpMENTAL pROCESSES IN MAMMALIAN EMBRYOS WITH OpTICAL COHERENCE TOMOGRApHY

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Journal of Innovative Optical Health Sciences 2009年第3期2卷 253-259页

作者： KIRILL V.larin IRINA V.larinA MICHAEL LIEBLING MARY E.DICKINSON Department of Biomedical Engineering University of Houston HoustonTXUSA Department of Molecular physiology and Biophysics Baylor College of Medicine HoustonTXUSA Department of Electrical and Computer Engineering University of California Santa BarbaraCAUSA

Early embryonic imaging of cardiovascular development in mammalian models requires a methodthat can penetrate through and distinguish the many tissue layers with high spatial and temporalresolution. In this paper we evaluate the capability of Optical Coherence Tomography (OCT)technique for structural 3D embryonic imaging in mouse embryos at different stages of thedevelopmental process ranging from 7.5 dpc up to 10.5 dpc. Obtained results suggest that thecollected data is suitable for quantitative and qualitative measurements to assess cardiovascularfunction in mouse models, which is likely to expand our knowledge of the complexity of theembryonic heart, and its development into an adult heart.

关键词： Optical Coherence Tomography non-invasive mouse embryos cardiovascular function.

Neural network-based image reconstruction in swept-source optical coherence tomography using undersampled spectral data

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Light(Science & Applications) 2021年第9期10卷 1658-1671页

作者： Yijie Zhang Tairan Liu Manmohan Singh EgeÇetintaş Yilin Luo Yair Rivenson Kirill V.larin Aydogan Ozcan Electrical and Computer Engineering Department University of CaliforniaLos AngelesCA90095USA Department of Bioengineering University of CaliforniaLos AngelesCA90095USA California NanoSystems Institute University of CaliforniaLos AngelesCA90095USA Department of Biomedical Engineering University of HoustonHoustonTX77204USA Department of Molecular physiology and Biophysics Baylor College of MedicineUniversity of HoustonHoustonTX77204USA Department of Surgery David Geffen School of MedicineUniversity of CaliforniaLos AngelesCA90095USA

Optical coherence tomography(OCT)is a widely used non-invasive biomedical imaging modality that can rapidly provide volumetric images of ***,we present a deep learning-based image reconstruction framework that can generate swept-source OCT(SS-OCT)images using undersampled spectral data,without any spatial aliasing *** neural network-based image reconstruction does not require any hardware changes to the optical setup and can be easily integrated with existing swept-source or spectral-domain OCT systems to reduce the amount of raw spectral data to be *** show the efficacy of this framework,we trained and blindly tested a deep neural network using mouse embryo samples imaged by an SS-OCT *** 2-fold undersampled spectral data(i.e.,640 spectral points per A-line),the trained neural network can blindly reconstruct 512 A-lines in 0.59 ms using multiple graphics-processing units(GpUs),removing spatial aliasing artifacts due to spectral undersampling,also presenting a very good match to the images of the same samples,reconstructed using the full spectral OCT data(i.e.,1280 spectral points per A-line).We also successfully demonstrate that this framework can be further extended to process 3×undersampled spectral data per A-line,with some performance degradation in the reconstructed image quality compared to 2×spectral ***,an A-line-optimized undersampling method is presented by jointly optimizing the spectral sampling locations and the corresponding image reconstruction network,which improved the overall imaging performance using less spectral data points per A-line compared to 2×or 3×spectral undersampling *** deep learning-enabled image reconstruction approach can be broadly used in various forms of spectral-domain OCT systems,helping to increase their imaging speed without sacrificing image resolution and signal-to-noise ratio.

关键词： graphics hardware image

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FOREWORD

Journal of Innovative Optical Health Sciences 2009年第1期2卷 I0001-I0002页

作者： Elina A.Genina Kirill V.larin Valery V.Tuchin Research-Educational Institute of Optics and Biophotonics Saratov State University Saratov Russia Department of Biomedical Engineering University of Houston Houston USA Research-Educational Institute of Optics and Biophotonics Saratov State University Institute of precise Mechanics and Control RAS Saratov Russia

Special Issue Optical Technologies in the Study of Tissues and Biological Fluids We are pleased to present this special issue of JIOHS,which focuses on optical technologies in the study of tissues and biological *** selected papers were presented during Saratov Fall Meeting—XII International School for Junior Scientists and Students on Optics,Laser physics and Biophotonics(September 23–26,2008,Saratov,Russia)in the framework of the following workshops:“Optical Technologies in Biophysics and Medicine,”“Nanostructures and Nanoparticles,”“Microscopic and Low-Coherence Methods in Biomedical Applications,”and“Internet Biophotonics.”All eight papers in this special issue are research papers.

关键词： Junior photonics Russia

In silico analysis of lncRNA-miRNA-mRNA signatures related to Sorafenib effectiveness in liver cancer cells

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World Journal of Gastroenterology 2025年第3期31卷 84-102页

作者： patricia de la Cruz-Ojeda Ester parras-Martínez Raquel Rey-pérez Jordi Muntané Functional Genomics of Solid Tumors Laboratory Centre de Recherche des CordeliersParis 75006France Department of Oncology Surgery Cell Therapy and Organ TransplantationInstitute of Biomedicine of SevilleVirgen del Rocio University HospitalSeville 41013Spain Biomedical Research Center for Hepatic and Digestive Diseases CIBERehdMadrid 28029Spain Department of Medical physiology and Biophysics University of SevilleSeville 41009Spain

BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of primary liver cancer with varied incidence and epidemiology *** is still a recommended treatment for a large proportion of patients with advanced *** patterns of treatment responsiveness have been identified in differentiated hepatoblastoma HepG2 cells and metastatic HCC SNU449 *** To define the long non-codingRNA-microRNA-mRNA(lncRNA-miRNA-mRNA)predicted signatures related to selected hallmarks of cancer(apoptosis,autophagy,cell stress,cell dedifferentiation and invasiveness)in RNAseq studies using Sorafenib-treated HepG2 and SNU449 *** available software analyses allowed us to establish the lncRNA-miRNA-mRNA regulatory axes following treatment in HepG2 and SNU449 *** HepG2 and SNU449 cells were treated with Sorafenib(10μmol/L)for 24 *** RNA,including small and long RNA,was extracted with a commercial miRNeasy *** was carried out for the identification of changes in lncRNA-miRNA-mRNA regulatory *** MALAT,THAp9-AS1 and SNGH17 appeared to coordinately regulate miR-374b-3p and miR-769-5p that led to upregulation of SMAD7,TIRARp,TFAp4 and FAXDC2 in HepG2 ***12,EpB41 L4A-AS1,LINC01578,SNHG12 and GAS5 interacted with let-7b-3p,miR-195-5p and VEGFA in SNU449 *** axes MALAT1/hsamir-374b-3p/SMAD7 and MALAT1/hsa-mir-769-5p/TFAp4 were of high relevance for Sorafenib response in HepG2 cells,whereas pVT1/hsa-miR-195-5p/VEGFA was responsible for the differential response of SNU449 cells to Sorafenib *** Critical lncRNAs acting as sponges of miRNA were identified that regulated mRNA expression,whose proteins mainly increased the antitumor effectiveness of the treatment(SMAD7,TIRARp,TFAp4,FAXDC2 and ADRB2).However,the broad regulatory axis leading to increased VEGFA expression may be related to the side effect of Sorafenib in SNU449 cells.

关键词： Cell culture Hepatocellular carcinoma Non-coding RNA RNAseq Sorafenib

On the Chain Length and Rate of Ozone Depletion in the Main Stratospheric Cycles

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Atmospheric and Climate Sciences 2013年第1期3卷 141-149页

作者： Igor larin Institute of Energy problems of Chemical physics Russian Academy of Sciences Moscow Russia

Algorithm for calculation of the chain length and rate of stratospheric ozone depletion in Ox, HOx, NOx, ClOx and BrOx cycles has been developed. The most important new element in the theory of stratospheric chain processes is the correct determination the propagation rate, taking into account all reactions involved rather than a single reaction, which has the lowest rate, as it was usually done before. The role of null chain processes in the cycles has been considered and shown that these processes play a decisive role in formation of families of the odd oxygen, nitrogen, chlorine and bromine in the daytime while at night they play no role. Using two-dimensional model Socrates, and algorithm developed correct rate of ozone depletion and chain length in the cycles above for model conditions of June 2020 at 50。N have been calculated.

关键词： Ozone Depletion Stratospheric Cycles Chain propagation Chain Limitation Limiting Step

Machine learning applications in healthcare clinical practice and research

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World Journal of Clinical Cases 2025年第1期13卷 16-21页

作者： Nikolaos-Achilleas Arkoudis Stavros p papadakos Research Unit of Radiology and Medical Imaging School of MedicineNational and Kapodistrian University of AthensAthens 11528Greece 2^(nd)Department of Radiology “Attikon”General University HospitalMedical SchoolNational and Kapodistrian University of AthensChaidari 12462Greece Department of Gastroenterology Laiko General HospitalNational and Kapodistrian University of AthensAthens 11527Greece

Machine learning(ML)is a type of artificial intelligence that assists computers in the acquisition of knowledge through data analysis,thus creating machines that can complete tasks otherwise requiring human *** its various applications,it has proven groundbreaking in healthcare as well,both in clinical practice and *** this editorial,we succinctly introduce ML applications and present a study,featured in the latest issue of the World Journal of Clinical *** authors of this study conducted an analysis using both multiple linear regression(MLR)and ML methods to investigate the significant factors that may impact the estimated glomerular filtration rate in healthy women with and without non-alcoholic fatty liver disease(NAFLD).Their results implicated age as the most important determining factor in both groups,followed by lactic dehydrogenase,uric acid,forced expiratory volume in one second,and *** addition,for the NAFLD-group,the 5th and 6th most important impact factors were thyroid-stimulating hormone and systolic blood pressure,as compared to plasma calcium and body fat for the NAFLD+***,the study's distinctive contribution lies in its adoption of ML methodologies,showcasing their superiority over traditional statistical approaches(herein MLR),thereby highlighting the potential of ML to represent an invaluable advanced adjunct tool in clinical practice and research.

关键词： Machine Learning Artificial Intelligence Clinical practice Research Glomerular filtration rate Non-alcoholic fatty liver disease Medicine

Small molecule inhibitor DDQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching

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Neural Regeneration Research 2025年第9期20卷 2624-2632页

作者： Jangampalli Adi pradeepkiran priyanka Rawat Arubala p.Reddy Erika Orlov pHemachandra Reddy Department of Internal Medicine Texas Tech University Health Sciences CenterLubbockTXUSA Department of Nutritional Sciences College of Human SciencesTexas Tech UniversityLubbockTXUSA Department of pharmacology&Neuroscience Texas Tech University Health Sciences CenterLubbockTXUSA Department of Neurology Texas Tech University Health Sciences CenterLubbockTXUSA Department of Speech Language and Hearing SciencesTexas Tech University Health Sciences CenterLubbockTXUSA Department of public Health Texas Tech University Health Sciences CenterLubbockTXUSA

The process of neurite outgrowth and branching is a crucial aspect of neuronal development and *** and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start *** we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal *** this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)*** investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were *** outgrowth is evaluated through the segmentation and measurement of neural *** neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite *** neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal ***-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAp-2,andβ-***,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic *** findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara *** key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.

关键词： diethyl(3 4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ) hippocampal neuronal cells HT22 neurite outgrowth neuronal development small molecule