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Dysregulated bidirectional epithelial-mesenchymal crosstalk:A core determinant of lung fibrosis progression

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第1期2卷 27-33页

作者： Liudi Yao Zijian Xu Donna E.Davies Mark G.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK Clinical and Experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK nihr southampton biomedical research centre University Hospital SouthamptonSouthampton SO166YDUK

Progressive lung fibrosis is characterized by dysregulated extracellular matrix(ECM)homeostasis.Understand-ing of disease pathogenesis remains limited and has prevented the development of effective treatments.While an abnormal wound-healing response is strongly implicated in lung fibrosis initiation,factors that determine why fi-brosis progresses rather than regular tissue repair occur are not fully explained.Within human lung fibrosis,there is evidence of altered epithelial and mesenchymal populations as well as cells undergoing epithelial-mesenchymal transition(EMT),a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell-cell adhesion to gain migratory properties.This review will focus on the role of EMT and dysregulated epithelial-mesenchymal crosstalk in progressive lung fibrosis.

关键词： Lung fibrosis Epithelial-mesenchymal transition(EMT) Crosstalk

Unveiling protein corona composition:predicting with resampling embedding and machine learning

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Regenerative Biomaterials 2024年第1期3卷 27-33页

作者： Rong Liao Yan Zhuang Xiangfeng Li Ke Chen Xingming Wang Cong Feng Guangfu Yin Xiangdong Zhu Jiangli Lin Xingdong Zhang College of biomedical Engineering National Engineering Research Centre for BiomaterialsSichuan UniversityChengdu610065China

Biomaterials with surface nanostructures effectively enhance protein secretion and stimulate tissue regeneration.When nanoparticles(NPs)enter the living system,they quickly interact with proteins in the body fluid,forming the protein corona(PC).The accurate prediction of the PC composition is critical for analyzing the osteoinductivity of biomaterials and guiding the reverse design of NPs.However,achieving accurate predictions remains a significant challenge.Although several machine learning(ML)models like Random Forest(RF)have been used for PC prediction,they often fail to consider the extreme values in the abundance region of PC absorption and struggle to improve accuracy due to the imbalanced data distribution.In this study,resampling embedding was introduced to resolve the issue of imbalanced distribution in PC data.Various ML models were evaluated,and RF model was finally used for prediction,and good correlation coefficient(R^(2))and root-mean-square deviation(RMSE)values were obtained.Our ablation experiments demonstrated that the proposed method achieved an R^(2) of 0.68,indicating an improvement of approximately 10%,and an RMSE of 0.90,representing a reduction of approximately 10%.Furthermore,through the verification of label-free quantification of four NPs:hydroxyapatite(HA),titanium dioxide(TiO_(2)),silicon dioxide(SiO_(2))and silver(Ag),and we achieved a prediction performance with an R^(2) value>0.70 using Random Oversampling.Additionally,the feature analysis revealed that the composition of the PC is most significantly influenced by the incubation plasma concentration,PDI and surface modification.

关键词： nanoparticles protein corona machine learming resampling technique feature analysis

Glucagon-like peptide 1 receptor activation:anti-inflammatory effects in the brain

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Neural Regeneration research 2024年第8期19卷 1671-1677页

作者： Yolanda Diz-Chaves Zainab Maastor Carlos Spuch José Antonio Lamas Lucas C.González-Matías Federico Mallo biomedical research centre(CINBIO) Laboratory of EndocrinologyUniversity of VigoGalicia Sur Health Research InstituteVigoSpain Translational Neuroscience research Group Galicia Sur Health Research InstituteCIBERSAMHospitalÁlvaro CunqueiroSala InvestigaciónEstrada Clara CampoamorVigoSpain biomedical research centre(CINBIO) Laboratory of NeuroscienceUniversity of VigoGalicia Sur Health Research InstituteVigoSpain

The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity.Glucagon-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain regions.Glucagon-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural morphogenesis.The glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous system.After brain insult,microglia are the first cells to respond,followed by reactive astrocytosis.These activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the insult.Furthermore,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many diseases.Several processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control mechanisms.The glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry response.This review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkinson’s disease,vascular dementia,or chronic migrai

关键词： astrocytes brain glucagon-like peptide 1 receptor inflammation microglia

Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

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Bio-Design and Manufacturing 2024年第2期7卷 121-136页

作者： Yang-Hee Kim Janos M.Kanczler Stuart Lanham Andrew Rawlings Marta Roldo Gianluca Tozzi Jonathan I.Dawson Gianluca Cidonio Richard O.C.Oreffo Faculty of Medicine Bone and Joint Research GroupCentre for Human DevelopmentStem Cells and RegenerationInstitute of Developmental SciencesUniversity of SouthamptonSouthampton SO166YDUK School of Pharmacy and biomedical Science University of PortsmouthPortsmouth PO12DTUK School of Engineering Faculty of Engineering and ScienceUniversity of GreenwichGreenwich ME44TBUK Center for Life Nano-and Neuro-Science(CLN2S) Italian Institute of Technology00161 RomeItaly

Autograft or metal implants are routinely used in skeletal repair.However,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering alternative.The use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor tissueregeneration.Thus,human bone extracellular matrix(bone-ECM)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBMSCs)to proliferate and differentiate along the osteogenic lineage.In this study,we engineered a novel material ink(LAB)by blending human bone-ECM(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based deposition.The inclusion of the nanoﬁller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBMSCs viability upon printing.The composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAM)model.The inclusion of bone morphogenetic protein-2(BMP-2)with the HBMSCs further enhanced vascularization and mineralization after only seven days.This study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECM)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

关键词： Extracellular matrix Nanoclay Bone 3D bioprinting

Ferroptosis mediators vary in metabolic syndrome,type-2 diabetes,and hypercholesterolemia:A meta-analysis report

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Genes & Diseases 2024年第3期11卷 109-112页

作者： Indra Kundu Ashlesha Pande Tannishtha Das Susan Idicula-Thomas biomedical Informatics centre Indian Council of Medical Research-National Institute for Research in Reproductive and Child HealthMumbaiMaharashtra 400012India Department of Biotechnology St.Xavier's CollegeKolkataWest Bengal 700016India

Metabolic syndrome(MetS)is a complex disorder characterized by the coexistence of phenotypes such as obesity,hypertension,hyperglycemia,high triglyceride level,and low level of high-density lipoprotein cholesterol.Inflammation majorly driven by oxidative stress has an overarching role in obesity and IR-mediated mechanisms leading to Mets.Besides these factors.

关键词： obesity cholesterol diabetes

Cell reprogramming therapy for Parkinson’s disease

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Neural Regeneration research 2024年第11期19卷 2444-2455页

作者： Wenjing Dong Shuyi Liu Shangang Li Zhengbo Wang State Key Laboratory of Primate biomedical research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunmingYunnan ProvinceChina Yunnan Key Laboratory of Primate biomedical research KunmingYunnan ProvinceChina

Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.

关键词： animal models astrocytes autologous cell reprogramming cell therapy direct lineage reprogramming dopaminergic neurons induced pluripotent stem cells non-human primates Parkinson’s disease

Loss of SHROOM3 affects neuroepithelial cell shape through regulating cytoskeleton proteins in cynomolgus monkey organoids

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Zoological research 2024年第2期45卷 233-241页

作者： Peng Li Ting Zhang Ruo Wu Jun-Yu Zhang Yan Zhuo Shan-Gang Li Jiao-Jian Wang Wen-Ting Guo Zheng-Bo Wang Yong-Chang Chen State Key Laboratory of Primate biomedical research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunmingYunnan 650500China Yunnan Key Laboratory of Primate biomedical research KunmingYunnan 650500China

Neural tube defects(NTDs)are severe congenital neurodevelopmental disorders arising from incomplete neural tube closure.Although folate supplementation has been shown to mitigate the incidence of NTDs,some cases,often attributable to genetic factors,remain unpreventable.The SHROOM3 gene has been implicated in NTD cases that are unresponsive to folate supplementation;at present,however,the underlying mechanism remains unclear.Neural tube morphogenesis is a complex process involving the folding of the planar epithelium of the neural plate.To determine the role of SHROOM3 in early developmental morphogenesis,we established a neuroepithelial organoid culture system derived from cynomolgus monkeys to closely mimic the in vivo neural plate phase.Loss of SHROOM3 resulted in shorter neuroepithelial cells and smaller nuclei.These morphological changes were attributed to the insufficient recruitment of cytoskeletal proteins,namely fibrous actin(F-actin),myosin II,and phospho-myosin light chain(PMLC),to the apical side of the neuroepithelial cells.Notably,these defects were not rescued by folate supplementation.RNA sequencing revealed that differentially expressed genes were enriched in biological processes associated with cellular and organ morphogenesis.In summary,we established an authentic in vitro system to study NTDs and identified a novel mechanism for NTDs that are unresponsive to folate supplementation.

关键词： Neural tube defects SHROOM3 Neuroepithelial Organoids Cynomolgus monkey

Circadian rhythm disruption and retinal dysfunction:a bidirectional link in Alzheimer’s disease?

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Neural Regeneration research 2024年第9期19卷 1967-1972页

作者： Laura Carrero DesireéAntequera Cristina Municio Eva Carro Group of Neurodegenerative Diseases Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpainNetwork Center for Biomedical Research in Neurodegenerative Diseases(CIBERNED)ISCIIIMadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurobiology of Alzheimer’s Disease Unit Functional Unit for Research into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpainNetwork Centre for Biomedical Research in Neurodegenerative Diseases(CIBERNED)ISCIIIMadridSpain

Dysfunction in circadian rhythms is a common occurrence in patients with Alzheimer’s disease.A predominant function of the retina is circadian synchronization,carrying information to the brain through the retinohypothalamic tract,which projects to the suprachiasmatic nucleus.Notably,Alzheimer’s disease hallmarks,including amyloid-β,are present in the retinas of Alzheimer’s disease patients,followed/associated by structural and functional disturbances.However,the mechanistic link between circadian dysfunction and the pathological changes affecting the retina in Alzheimer’s disease is not fully understood,although some studies point to the possibility that retinal dysfunction could be considered an early pathological process that directly modulates the circadian rhythm.

关键词： Alzheimer’s disease amyloid circadian rhythm neurodegeneration retina

An end‐to‐end infant brain parcellation pipeline

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Intelligent Medicine 2024年第2期4卷 65-74页

作者： Limei Wang Yue Sun Weili Lin Gang Li Li Wang Department of Radiology and biomedical research Imaging Center UNC-Chapel HillNew Caledonia27599USA

Objective Accurate infant brain parcellation is crucial for understanding early brain development;however,it is challenging due to the inherent low tissue contrast,high noise,and severe partial volume effects in infant magnetic resonance images(MRIs).The aim of this study was to develop an end-to-end pipeline that enabled accurate parcellation of infant brain MRIs.Methods We proposed an end-to-end pipeline that employs a two-stage global-to-local approach for accurate parcellation of infant brain MRIs.Specifically,in the global regions of interest(ROIs)localization stage,a combination of transformer and convolution operations was employed to capture both global spatial features and fine texture features,enabling an approximate localization of the ROIs across the whole brain.In the local ROIs refinement stage,leveraging the position priors from the first stage along with the raw MRIs,the boundaries of the ROIs are refined for a more accurate parcellation.Results We utilized the Dice ratio to evaluate the accuracy of parcellation results.Results on 263 subjects from National Database for Autism research(NDAR),Baby Connectome Project(BCP)and Cross-site datasets demonstrated the better accuracy and robustness of our method than other competing methods.Conclusion Our end-to-end pipeline may be capable of accurately parcellating 6-month-old infant brain MRIs.

关键词： Infant brain parcellation Isointense magnetic resonance image Convolutional neural networks Transformer