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Cancer cell cycle heterogeneity as a critical determinant of therapeutic resistance

Genes & Diseases 2024年第1期11卷 189-204页

作者： Ebrahim H.Maleki Ahmad Reza Bahrami Maryam M.Matin Department of Biology Faculty of ScienceFerdowsi University of Mashhad*** MashhadIran Jagiellonian Centre for Experimental Therapeutics(JCET) Jagiellonian University31-007 KrakowPoland Doctoral School of Exact and Natural Sciences Jagiellonian University30-348 KrakowPoland Industrial biotechnology research group Institute of BiotechnologyFerdowsi University of Mashhad*** MashhadIran Novel Diagnostics and Therapeutics research group Institute of BiotechnologyFerdowsi University of Mashhad***MashhadIran Stem cell and regenerative medicine research group Iranian Academic Center for EducationCulture and Research(ACECR)Khorasan Razavi Branch917751376 MashhadIran

Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology,as it represents a major obstacle to effective cancer *** tumor cells are highly diverse at genetic,epigenetic,and phenotypic levels,intra-tumor heterogeneity can be assumed as an important contributing factor to the nullification of chemotherapeutic effects,and recurrence of the *** on the role of heterogeneous subpopulations of cancer cells with varying cell-cycle dynamics and behavior during cancer progression and treatment;herein,we aim to establish a comprehensive definition for adaptation of neoplastic cells against *** discuss two parallel and yet distinct subpopulations of tumor cells that play pivotal roles in reducing the effects of chemotherapy:"resistant"and"tolerant"***,this review also highlights the impact of the quiescent phase of the cell cycle as a survival mechanism for cancer *** understanding the mechanisms under-lying the quiescence,it provides an insightful perspective on cancer stem cells(CsCs)and their dual and intertwined functions based on their cell cycle state in response to ***-over,CSCs,epithelial-mesenchymal transformed cells,circulating tumor cells(CTCs),and disseminated tumor cells(DTCs),which are mostly in a quiescent state of the cell cycle are proved to have multiple biological links and can be implicated in our viewpoint of cell cycle heterogeneity in ***,increasing our knowledge of cell cycle heterogeneity is a key to identifying new therapeutic solutions,and this emerging concept may provide us with new opportunities to prevent the dreadful cancer recurrence.

关键词： Cancer stem cells(CSCs) Carcinoma cell cycle heterogeneity Quiescence therapy resistance therapy tolerance Tumor dormancy

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The Effect of Spironolactone Loading on the Properties of 3D-Printed Polycaprolactone/Gold Nanoparticles Composite Scaffolds for Myocardial Tissue Engineering

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Journal of Bionic Engineering 2024年第2期21卷 924-937页

作者： Sharareh Ghaziof Shahrokh Shojaei Mehdi Mehdikhani Mohammad Khodaei Milad Jafari Nodoushan Department of Biomedical Engineering Central Tehran BranchIslamic Azad UniversityTehran***Iran Stem cells research Center Tissue Engineering and Regenerative Medicine InstituteCentral Tehran BranchIslamic Azad UniversityTehran***Iran Department of Biomedical Engineering Faculty of EngineeringUniversity of IsfahanIsfahan***Iran Materials Engineering group Golpayegan College of EngineeringIsfahan University of TechnologyGolpayegan87717-67498Iran Hard Tissue Engineering research Center Tissue Engineering and Regenerative Medicine InstituteCentral Tehran BranchIslamic Azad UniversityTehran***Iran

Engineered cardiac constructs(ECC)aid in the progression of regenerative medicine,disease modeling and targeted drug delivery to adjust and aim the release of remedial combination as well as decrease the side effects of *** this research,polycaprolactone/gold nanoparticles(PCL/GNPs)three-dimensional(3D)composite scaffolds were manufactured by 3D printing using the fused deposition modeling(FDM)method and then coated with gelatin/spironolactone(GEL/SPL).Scanning electron microscopy(SEM)and Fourier transform-infrared spectroscopy(FTIR–ATR)were applied to characterize the ***,drug release,biodegradation,behavior of the myoblasts(H9C2)cell line,and cytotoxicity of the 3D scaffolds were *** microstructural observation of the scaffolds reported interconnected pores with 150–300µm in *** 3D scaffolds were degraded significantly after 28 days of immersion in stimulated body fluid(SBF),with the maximum rate of GEL-coated 3D *** release from cross-linked GEL coating demonstrated the excess of drug release over time,and according to the control release systems,the drug delivery systems(DDS)went into balance after the 14th *** addition,cell culture study showed that with the addition of GNPs,the proliferation of(H9C2)was enhanced,and with GEL/SPL coating the cell attachment and viability were improved *** findings suggested that PCL/GNPs 3D scaffolds coated with GEL/SPL can be an appropriate choice for myocardial tissue engineering.

关键词： Polycaprolactone Gold nanoparticles Drug delivery systems Spironolactone cell behavior Myoblasts

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A pathological joint-liver axis mediated by matrikine-activated CD4^(+)T cells

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Signal Transduction and Targeted therapy 2024年第6期9卷 2679-2693页

作者： Junzhi Yi Hui Zhang Fangyuan Bao Zhichu Chen Yuliang Zhong Tianning Ye Xuri Chen Jingyi Qian Mengya Tian Min Zhu Zhi Peng Zongyou Pan Jianyou Li Zihao Hu Weiliang Shen Jiaqi Xu Xianzhu Zhang Youzhi Cai Mengjie Wu Hua Liu Jing Zhou Hongwei Ouyang Department of Sports medicine of the Second Affiliated Hospital and Liangzhu LaboratoryZhejiang University School of MedicineHangzhouChina Dr.Li Dak Sum&Yip Yio Chin Center for Stem cells and regenerative medicine Zhejiang University School of MedicineHangzhouChina Stomatology Hospital School of StomatologyZhejiang University School of MedicineZhejiang Provincial Clinical Research Center for Oral DiseasesHangzhouChina The MOE Key Laboratory of Biosystems Homeostasis&Protection The Key Laboratory of Cancer Molecular Cell Biology of Zhejiang ProvinceLife Sciences InstituteZhejiang UniversityHangzhouChina Department of Orthopedics Huzhou Central HospitalAffiliated Huzhou HospitalZhejiang University School of MedicineHuzhouChina China Orthopedic regenerative medicine group(CORMed) HangzhouChina Department of Orthopedics The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina

The knee joint has long been considered a closed *** pathological effects of joint diseases on distant organs have not been ***,our clinical data showed that post-traumatic joint damage,combined with joint bleeding(hemarthrosis),exhibits a worse liver function compared with healthy *** mouse model,hemarthrosis induces both cartilage degeneration and remote liver ***,we found that hemarthrosis induces the upregulation in ratio and differentiation towards Th17 cells of CD4^(+)T cells in peripheral blood and *** of CD4^(+)T cells reverses hemarthrosis-induced liver *** of cartilage matrix induced by hemarthrosis upregulates serological type Ⅱ collagen(COL Ⅱ),which activates CD4^(+)T *** application of a COL Ⅱ antibody blocks the ***,bulk RNAseq and single-cell qPCR analysis revealed that the cartilage Akt pathway is inhibited by blood ***-articular application of Akt activator blocks the cartilage degeneration and thus protects against the liver impairment in mouse and pig *** together,our study revealed a pathological joint-liver axis mediated by matrikine-activated CD4^(+)T cells,which refreshes the organ-crosstalk axis and provides a new treatment target for hemarthrosis-related disease.

关键词： degeneration damage inhibited

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Allogeneic mesenchymal stem cells may be a viable treatment modality in cerebral palsy

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World Journal of Clinical Cases 2024年第9期12卷 1585-1596页

作者： Osman Boyalı Serdar Kabatas ErdinçCivelek Omer Ozdemir Yeliz Bahar-Ozdemir Necati Kaplan Eyüp Can Savrunlu Erdal Karaöz Department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalIstanbul 34360Turkey Center for Stem cell&Gene therapy research and Practice University of Health Sciences TurkeyIstanbul 34360Turkey Department of Physical medicine and Rehabilitation Health Sciences University Sultan Abdulhamid Han Training and Research HospitalIstanbul 34668Turkey Department of Neurosurgery Istanbul Rumeli UniversityÇorlu Reyap HospitalTekirdağ59860Turkey Department of Neurosurgery Nevşehir State HospitalNevşehir 50300Turkey Center for regenerative medicine and Stem cell research&Manufacturing(LivMedcell) Liv HospitalIstanbul 34340Turkey Department of Histology and Embryology Istinye UniversityFaculty of Medicineİstanbul 34010Turkey Center for Stem cell and Tissue Engineering research and Practice Istinye UniversityIstanbul 34340Turkey

BACKGROUND Cerebral palsy(CP)describes a group of disorders affecting movement,balance,and *** in motor functions constitute the main body of CP *** symptoms surface in early childhood and patients are affected for the rest of their ***,treatment involves various pharmacotherapies for different types of CP,including antiepileptics for epilepsy and Botox A for focal ***,none of these methods can provide full symptom *** has prompted researchers to look for new treatment modalities,one of which is mesenchymal stem cell therapy(MSCT).Despite being a promising tool and offering a wide array of possibilities,mesenchymal stem cells(MSCs)still need to be investigated for their efficacy and *** To analyze the efficacy and safety of MSCT in CP *** Our sample consists of four CP patients who cannot stand or walk without external *** of these cases received allogeneic MSCT six times as 1×106/kg intrathecally,intravenously,and intramuscularly using umbilical cord-derived MSCs(UC-MSC).We monitored and assessed the patients pre-and post-treatment using the Wee Functional Independence Measure(WeeFIM),Gross Motor Function Classification System(GMFCS),and Manual Ability Classification Scale(MACS)*** utilized the Modified Ashworth Scale(MAS)to measure *** We found significant improvements in MAS scores after the intervention on both *** months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;four months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;12 months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=***,there was no significant difference in motor functions based on WeeFIM results(P>0.05).GMFCS and MACS scores differed significantly at 12 months after the intervention(P=0.046,P=0.046).Finally,there was no significant change in cognitive functions(P>0.05).CONCLUSION In light of our findings,we believe that UC-MSC therapy has a positive effect on spasticity

关键词： Cerebral palsy Mesenchymal stem cell Transplantation Wharton’s jelly Muscle spasticity

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A facile strategy for tuning the density of surface-grafted biomolecules for melt extrusion-based additive manufacturing applications

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Bio-Design and Manufacturing 2024年第3期7卷 277-291页

作者： I.A.O.Beeren G.Dos Santos P.J.Dijkstra C.Mota J.Bauer H.Ferreira Rui L.Reis N.Neves S.Camarero-Espinosa M.B.Baker L.Moroni Department of Complex Tissue Regeneration MERLN Institute for Technology-Inspired Regenerative MedicineMaastricht University6229 ER MaastrichtThe Netherlands 3B’s research group I3Bs–Research Institute on BiomaterialsBiodegradables and BiomimeticsHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineUniversity of MinhoAveParkZona Industrial da Gandra4805-017 BarcoGuimarãesPortugal ICVS/3B’s-PT Government Associate Laboratory 4806-909 Braga/GuimarãesPortugal POLYMAT University of the Basque Country UPV/EHU20018 Donostia/San SebastiánSpain IKERBASQUE Basque Foundation for Science48009 BilbaoSpain

Melt extrusion-based additive manufacturing(ME-AM)is a promising technique to fabricate porous scaffolds for tissue engi-neering ***,most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell *** of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct;however,there are limited strategies available to control the surface ***,we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k(PCL5k)containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCL75k at different *** porous three-dimensional(3D)scaf-folds were then fabricated using a high weight percentage(75 wt.%)of the low molecular weight PCL *** a proof-of-concept test,we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface,yielding a density of 201-561 pmol/cm^(2).Subsequently,a bone morphogenetic protein 2(BMP-2)-derived peptide was grafted onto the films comprising different blend compositions,and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells(hMSCs)was *** two weeks of culturing in a basic medium,cells expressed higher levels of BMP receptor II(BMPRII)on films with the conjugated *** addition,we found that alkaline phosphatase activity was only significantly enhanced on films contain-ing the highest peptide density(i.e.,561 pmol/cm^(2)),indicating the importance of the surface *** together,these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material ***,we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of(m

关键词： Additive manufacturing Blending Surface functionalization Surface density Click chemistry Human

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Biomaterials and emerging technologies for tissue engineering and in vitro models

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Bio-Design and Manufacturing 2024年第3期7卷 237-239页

作者： J.Miguel Oliveira Rui L.Reis 3B’s research group I3Bs-Research Institute on BiomaterialsBiodegradables and BiomimeticsHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineUniversity of MinhoAveParkZona Industrial da Gandra4805-017 BarcoGuimarãesPortugal ICVS/3B’s-PT Government Associate Laboratory 4806-909 Braga/GuimarãesPortugal

The latest advances in the field of biomaterials have opened new avenues for scientific breakthroughs in tissue engineer-ing which greatly contributed for the successful translation of tissue engineering products into the market/***-materials are easily processed to become similar to natural extracellular matrix,making them ideal temporary supports for mimicking the three-dimensional(3D)microenvironment required for maintaining the adequate cell/tissue functions both in vitro and in vivo^([1]).

关键词： breakthrough biomaterials engineer

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Efficacy of stromal vascular fraction for knee osteoarthritis:A prospective,single-centre,non-randomized study with 2 years follow-up

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World Journal of Orthopedics 2024年第5期15卷 457-468页

作者： Madhan Jeyaraman Naveen Jeyaraman Tarun Jayakumar Swaminathan Ramasubramanian Rajni Ranjan Saurabh Kumar Jha Ashim Gupta Department of Orthopaedics ACS Medical College and HospitalDr MGR Educational and Research InstituteChennaiTamil Nadu 600077India Department of biotechnology School of Engineering and TechnologySharda UniversityGreater NoidaUttar Pradesh 201310India Department of Orthopaedics and regenerative medicine South Texas Orthopaedic Research InstituteLaredoTX 78045United States Department of Orthopaedics KIMS-Sunshine HospitalHyderabadTelangana 500032India Department of Orthopaedics Government Medical CollegeOmandurar Government EstateChennaiTamil Nadu 600002India Department of Orthopaedics School of Medical Sciences and ResearchSharda UniversityGreater NoidaUttar Pradesh 201306India Department of Zoology Kalindi CollegeUniversity of DelhiNew Delhi 110008India Department of Orthopaedics and regenerative medicine Regenerative OrthopaedicsNoida 201301Uttar PradeshIndia Department of Orthopaedics and regenerative medicine Future BiologicsLawrencevilleGA 30043United States Department of Orthopaedics and regenerative medicine BioIntegrateLawrencevilleGA 30043United States

BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease *** regenerative medicine,current treatments have *** regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism *** To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee *** The study included 50 patients with Kellgren-Lawrence grades II and III *** were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)*** were followed up at 1,3,6,12,and 24 *** analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all *** safety of SVF in terms of adverse and severe adverse events was *** analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United *** Both groups had similar demographics and baseline clinical ***-up showed minor patient loss,resulting in 23 and 24 in groups A and B *** A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in group *** difference in pain reduction in group A was statistically significant from the third month ***,group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas group B saw a modest increase from 36.7 to *** improvement in group A was statistically significant from 6 months and maintained through 24 *** Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in pa

关键词： Knee osteoarthritis Adipose tissue Stromal vascular fraction regenerative medicine Orthobiologics

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Spatial transcriptomics:recent developments and insights in respiratory research

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Military Medical research 2024年第3期11卷 430-448页

作者： Wen-Jia Wang Liu-Xi Chu Li-Yong He Ming-Jing Zhang Kai-Tong Dang Chen Gao Qin-Yu Ge Zhou-Guang Wang Xiang-Wei Zhao State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Oujiang Laboratory(Zhejiang Lab for regenerative medicine Vision and Brain Health)School of Pharmaceutical SciencesWenzhou Medical UniversityWenzhou 325035ZhejiangChina Orthopaedic Bioengineering research group Division of Surgery and Interventional ScienceUniversity College LondonLondon HA74LPUK

The respiratory system's complex cellular heterogeneity presents unique challenges to researchers in this *** bulk RNA sequencing and single-cell RNA sequencing(scRNA-seq)have provided insights into cell types and heterogeneity in the respiratory system,the relevant specific spatial localization and cellular interactions have not been clearly *** transcriptomics(ST)has filled this gap and has been widely used in respiratory *** review focuses on the latest iterative technology of ST in recent years,summarizing how ST can be applied to the physiological and pathological processes of the respiratory system,with emphasis on the ***,the current challenges and potential development directions are proposed,including high-throughput full-length transcriptome,integration of multi-omics,temporal and spatial omics,bioinformatics analysis,*** viewpoints are expected to advance the study of systematic mechanisms,including respiratory studies.

关键词： Spatial transcriptomics Lung Tumor Spatial multi-omics

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cellular interplay to 3D in vitro microphysiological disease model:cell patterning microbiota-gut-brain axis

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Bio-Design and Manufacturing 2024年第3期7卷 320-357页

作者： Kamare Alam Lakshmi Nair Souvik Mukherjee Kulwinder Kaur Manjari Singh Santanu Kaity Velayutham Ravichandiran Sugato Banerjee Subhadeep Roy Department of Pharmacology and Toxicology National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India Department of Pharmaceutical Sciences Assam UniversitySilchar 788011India Department of Pharmaceutical Sciences Guru Ghasidas UniversityKoniBilaspur 495009C.G.India School of Pharmacy and Biomolecular Sciences RCSI University of Medicine and Health SciencesDublin D02 YN77Ireland Tissue Engineering research group Department of Anatomy and Regenerative MedicineRCSI University of Medicine and Health SciencesDublin D02 YN77Ireland Department of Pharmaceutics National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India Department of Natural Products National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India

The microbiota-gut-brain axis(MGBA)has emerged as a key prospect in the bidirectional communication between two major organ systems:the brain and the *** between the two organ systems allows the body to function without disease,whereas dysbiosis has long-standing evidence of etiopathological *** most common communication paths are the microbial release of metabolites,soluble neurotransmitters,and immune ***,each pathway is intertwined with a complex *** the emergence of in vitro models and the popularity of three-dimensional(3D)cultures and Transwells,engineering has become easier for the scientific understanding of neurodegenerative *** paper briefly retraces the possible communication pathways between the gut microbiome and the *** further elaborates on three major diseases:autism spectrum disorder,Parkinson’s disease,and Alzheimer’s disease,which are prevalent in children and the *** diseases also decrease patients’quality of ***,understanding them more deeply with respect to current advances in in vitro modeling is crucial for understanding the *** of MGBA in the laboratory uses many molecular technologies and biomaterial *** and organoids provide a more realistic picture of the cell and tissue structure than *** them with the Transwell system offers the advantage of compartmentalizing the two systems(apical and basal)while allowing physical and chemical cues between ***-edge technologies,such as bioprinting and microfluidic chips,might be the future of in vitro modeling,as they provide dynamicity.

关键词： Microbiota-gut-brain axis Neurodegeneration 3D disease model Organoid Transwell system

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New insights into the therapeutic approaches for the treatment of tauopathies

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Neural Regeneration research 2024年第5期19卷 1020-1026页

作者： Himanshi Singh Asmita Das Mohammad Moshahid Khan Tayebeh Pourmotabbed Department of Microbiology Immunology and BiochemistryUniversity of Tennessee Health Science CenterMemphisTNUSA Department of biotechnology Delhi Technological UniversityShahbad DaulatpurDelhiIndia Department of Neurology College of MedicineUniversity of Tennessee Health Science CenterMemphisTNUSA Neuroscience Institute University of Tennessee Health Science CenterMemphisTNUSA Center for Muscle Metabolism and NeuropathologyDivision of Regenerative and Rehabilitation Sciences and Department of Physical TherapyCollege of Health ProfessionsUniversity of Tennessee Health Science CenterMemphisTNUSA

Tauopathies are a group of neurological disorders,including Alzheimer’s disease and frontotemporal dementia,which involve progressive neurodegeneration,cognitive deficits,and aberrant tau protein *** development of tauopathies cannot currently be stopped or slowed down by treatment *** the significant contribution of tau burden in primary tauopathies and the strong association between pathogenic tau accumulation and cognitive deficits,there has been a lot of interest in creating therapies that can alleviate tau pathology and render neuroprotective ***,small molecules,immunotherapies,and gene therapy have been used to reduce the pathological tau burden and prevent neurodegeneration in animal models of ***,the major pitfall of the current therapeutic approach is the difficulty of drugs and gene-targeting modalities to cross the blood-brain barrier and their unintended side *** this review,the current therapeutic strategies used for tauopathies including the use of oligonucleotide-based gene therapy approaches that have shown a promising result for the treatment of tauopathies and Alzheimer’s disease in preclinical animal models,have been discussed.

关键词： dementia gene therapies immunotherapy neurodegeneration oligonucleotides tau tauopathies therapies

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