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Neural Regeneration Research 2024年第10期19卷 2189-2201页

作者： Jesus Amo-Aparicio Charles A.Dinarello Ruben Lopez-Vales Department of Medicine University of ColoradoAuroraCOUSA Institute of Neurosciences and Department Cell BiologyPhysiology and ImmunologyUniversitat Autònoma de BarcelonaBellaterraSpain Centro de Investigación Biomédica en red sobre Enfermedades Neurodegenerativas(CIBERNED) Instituto de Salud Carlos ⅢSpain

Metabolism is a fundamental process by which biochemicals are broken down to produce energy(catabolism) or used to build macromolecules(anabolism). Metabolism has received renewed attention as a mechanism that generates molecules that modulate multiple cellular responses. This was first identified in cancer cells as the Warburg effect, but it is also present in immunocompetent cells. Studies have revealed a bidirectional influence of cellular metabolism and immune cell function, highlighting the significance of metabolic reprogramming in immune cell activation and effector functions. Metabolic processes such as glycolysis, oxidative phosphorylation, and fatty acid oxidation have been shown to undergo dynamic changes during immune cell response, facilitating the energetic and biosynthetic demands. This review aims to provide a better understanding of the metabolic reprogramming that occurs in different immune cells upon activation, with a special focus on central nervous system disorders. Understanding the metabolic changes of the immune response not only provides insights into the fundamental mechanisms that regulate immune cell function but also opens new approaches for therapeutic strategies aimed at manipulating the immune system.

关键词： central nervous system fatty acid oxidation glycolysis inflammation macrophage metabolism microglia neurodegeneration oxidative phosphorylation

Isoform-and cell-state-specific APOE homeostasis and function

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Neural Regeneration Research 2024年第11期19卷 2456-2466页

作者： Karina Lindner Anne-Claude Gavin Department of cell physiology and Metabolism Faculty of MedicineUniversity of GenevaGenevaSwitzerland Diabetes Center Faculty of MedicineUniversity of GenevaGenevaSwitzerland

Apolipoprotein E is the major lipid transporter in the brain and an important player in neuron-astrocyte metabolic coupling.It ensures the survival of neurons under stressful conditions and hyperactivity by nourishing and detoxifying them.Apolipoprotein E polymorphism,combined with environmental stresses and/or age-related alterations,influences the risk of developing late-onset Alzheimer’s disease.In this review,we discuss our current knowledge of how apolipoprotein E homeostasis,i.***.its synthesis,secretion,degradation,and lipidation,is affected in Alzheimer’s disease.

关键词： Alzheimer’s disease apolipoprotein E autophagy cholesterol lipid detoxification lipid transport lysosomal failure metabolic impairment triacylglycerol

Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

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Neural Regeneration Research 2024年第6期19卷 1318-1324页

作者： Theodora Mourtzi Nasia Antoniou Christina Dimitriou Panagiotis Gkaravelas Georgia Athanasopoulou Panagiota Nti Kostantzo Olga Stathi Efthymia Theodorou Maria Anesti Rebecca Matsas Fevronia Angelatou Georgia Kouroupi Ilias Kazanis laboratory of Developmental Biology Department of Biology University of Patras laboratory of cellular and Molecular Neurobiology-Stem cells Hellenic Pasteur Institute 3. Department of Physiology School of Medicine University of Patras

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the “weaver” mouse, a model of progressive nigrostriatal degeneration. Here, we extended our investigation in two clinically-relevant ways. First, we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors. Second, we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice, at late stages of degeneration. We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells, marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors. In agreement, we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice. However, the graft strongly induced an endogenous neurogenic response throughout the midbrain, which was significantly enhanced by the administration of microneurotrophin BNN-20. Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20. Interestingly, the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.

关键词： adult neurogenesis BNN-20 brain-derived neurotrophic factor cell replacement induced pluripotent stem cells (iPSCs) neurotrophic factors Parkinson's disease substantia

Endomembrane-biased dimerization of ABCG16 and ABCG25 transporters determines their substrate selectivity in ABA-regulated plant growth and stress responses

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Molecular Plant 2024年第3期17卷 478-495页

作者： Yeling Zhou Yuzhu Wang Dong Zhang Jiansheng Liang institute of Plant and Food Science Department of BiologySchool of Life SciencesSouthern University of Science and Technology(SUSTech)Shenzhen 518055China Key laboratory of Molecular Design for Plant cell Factory of Guangdong Higher Education Institutes Southern University of Science and Technology(SUSTech)Shenzhen 518055China jiangsu Key laboratory of Crop Genetics and physiology/Co-lnnovation Center for Modern Production Technology of Grain Crops Key Laboratory of Plant Functional Genomics of the Ministry of EducationYangzhou UniversityYangzhou 225009China

ATP-binding cassette(ABC)transporters are integral membrane proteins that have evolved diverse func-tions fulfilled via the transport of various substrates.In Arabidopsis,the G subfamily of ABC proteins is particularly abundant and participates in multiple signaling pathways during plant development and stress responses.In this study,we revealed that two Arabidopsis ABCG transporters,ABCG16 and ABCG25,engage in ABA-mediated stress responses and early plant growth through endomembrane-specific dimerization-coupled transport of ABA and ABA-glucosyl ester(ABA-GE),respectively.We first revealed that ABCG16 contributes to osmotic stress tolerance via ABA signaling.More specifically,ABCG16 induces cellular ABA efflux in both yeast and plant cells.Using FRET analysis,we showed that ABCG16 forms oblig-atory homodimers for ABA export activity and that the plasma membrane-resident ABCG16 homodimers specifically respond to ABA,undergoing notable conformational changes.Furthermore,we demonstrated that ABCG16 heterodimerizes with ABCG25 at the endoplasmic reticulum(ER)membrane and facilitates the ER entry of ABA-GE in both Arabidopsis and tobacco cells.The specific responsiveness of the ABCG16-ABCG25 heterodimer to ABA-GE and the superior growth of their double mutant support an inhib-itory role of these twoABCGs in early seedling establishment via regulation of ABA-GE translocation across the ER membrane.Our endomembrane-specific analysis of the FRET signals derived from the homo-or heterodimerized ABcG complexes allowed us to link endomembrane-biased dimerization to the transloca-tion of distinct substrates by ABcG transporters,providing a prototypic framework for understanding the omnipotence of ABcG transporters in plant development and stress responses.

关键词： abscisic acid ABCG transporter dimerization endomembrane substrate selectivity

Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis

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Chinese Medical Journal 2024年第2期137卷 181-189页

作者： Fangming Liu Yuting Wu Baohui Zhang Shuhui Yang Kezhuo Shang Jie Li Pengju Zhang Weiwei Deng Linlin Chen Liang Zheng Xiaochen Gai Hongbing Zhang Department of physiology State Key Laboratory of Common Mechanism Research for Major DiseasesHaihe Laboratory of Cell EcosystemInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China Department of physiology Institute of Basic Medical Sciences and School of Basic MedicineGraduate School of Peking Union Medical CollegeChinese Academy of Medical SciencesBeijing100005China Department of physiology School of Life ScienceChina Medical UniversityShenyangLiaoning 110122China School of Life Sciences Westlake UniversityHangzhouZhejiang 310024China Key laboratory of Pediatric Hematology and Oncology Ministry of HealthInstitute of Pediatric Translational MedicineShanghai Children’s Medical CenterShanghai Jiao Tong School of MedicineShanghai 200127China

Background:Liver cancer is largely resistant to chemotherapy.This study aimed to identify the effective chemotherapeutics forβ-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1(CTNNB1),the most frequently altered proto-oncogene in hepatic neoplasms.Methods:Constitutiveβ-catenin-activated mouse embryonic fibroblasts(MEFs)were established by deleting exon 3(β-catenin^(Δ(ex3)/+)),the most common mutation site in CTNNB1 gene.A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibitedβ-catenin^(Δ(ex3)/+)but not for wild-type MEFs.Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis.The efficacy and selectivity of methotrexate(MTX)onβ-catenin-activated human liver cancer cells were determined in vitro.Immuno-deficient nude mice subcutaneously inoculated withβ-catenin wild-type or mutant liver cancer cells and hepatitis B virus(HBV);β-catenin^(lox(ex3)/+)mice were used,respectively,to evaluate the efficacy of MTX in the treatment ofβ-catenin mutant liver cancer.Results:MTX was identified and validated as a preferential agent against the proliferation and tumor formation ofβ-catenin-activated cells.Boosted nucleotide synthesis was the major metabolic aberration inβ-catenin-active cells,and this alteration was also the target of MTX.Moreover,MTX abrogated hepatocarcinogenesis of HBV;β-catenin^(lox(ex3)/+)mice,which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer.Conclusion:MTX is a promising chemotherapeutic agent forβ-catenin hyperactive liver cancer.Since repurposing MTX has the advantages of lower risk,shorter timelines,and less investment in drug discovery and development,a clinical trial is warranted to test its efficacy in the treatment ofβ-catenin mutant liver cancer.

关键词： Liver cancer β-catenin Methotrexate Nucleotide synthesis Chemotherapy

MicroRNAs in thyroid cancer with focus on medullary thyroid carcinoma:potential therapeutic targets and diagnostic/prognostic markers and web based tools

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Oncology Research 2024年第6期32卷 1011-1019页

作者： ELHAM SHAKIBA SETI BOROOMAND SIMA KHERADMAND KIA MEHDI HEDAYATI Department of Biochemistry Faculty of Biological SciencesNorth Tehran BranchIslamic Azad UniversityTehran***Iran Department of Pathology and laboratory Medicine Vancouver General HospitalVancouverV5Z 1M9Canada Department of Blood cell Research Laboratory for Red Blood Cell DiagnosticsSanquinAmsterdam1006 ANThe Netherlands cellular and Molecular Endocrine Research Center Research Institute for Endocrine SciencesShahid Beheshti University of Medical SciencesTehran***Iran

This review aimed to describe the inculpation of microRNAs(miRNAs)in thyroid cancer(TC)and its subtypes,mainly medullary thyroid carcinoma(MTC),and to outline web-based tools and databases for bioinformatics analysis of miRNAs in TC.Additionally,the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be discussed.This review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes,mainly MTC.Additionally,web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and described.MiRNAs can perform as oncomiRs or antioncoges,relying on the target mRNAs they regulate.MiRNA replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases,particularly in cancer.MiRNAs are involved in the modulation of fundamental pathways related to cancer,resembling cell cycle checkpoints and DNA repair pathways.MiRNAs are also rather stable and can reliably be detected in different types of biological materials,rendering them favorable diagnosis and prognosis biomarkers as well.MiRNAs have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic targets.The contribution of miRNAs in thyroid cancer,particularly MTC,is an active area of research,and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.

关键词： Thyroid cancer MicroRNAs Biomarker Bioinformatics analysis Medullary thyroid carcinoma(MTC) OncomiRs Antioncoges

Proteomic response of Phaeocystis globosa to nitrogen limitation

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Journal of Oceanology and Limnology 2024年第1期42卷 141-149页

作者： Haisu LIU Ruiwang WEI Qiangyong LEI Lei CUI Songhui LÜ Key laboratory of Eutrophication and red Tide Prevention Research Center for Harmful Algae and Marine BiologyJinan UniversityGuangzhou 510632China Southern Marine Science and Engineering Guangdong laboratory Zhuhai 519082China National Engineering laboratory of Electronic and Information Standardization Shenzhen 518057China

Phaeocystis globosa is an important unicellular eukaryotic alga that can also form colonies.P.globosa can cause massive harmful algal blooms and plays an important role in the global carbon or sulfur cycling.Thus far,the ecophysiology of P.globosa has been investigated by numerous studies.However,the proteomic response of P.globosa to nitrogen depletion remains largely unknown.We compared four protein preparation methods of P.globosa for two-dimensional electrophoresis(2-DE)(Urea/Triton X-100 with trichloroacetic acid(TCA)/acetone precipitation;TCA/acetone precipitation;Radio Immuno Precipitation Assay(RIPA)with TCA/acetone precipitation;and Tris buffer).Results show that the combination of RIPA with TCA/acetone precipitation had a clear gel background and showed the best protein spot separation effect,based on which the proteomic response to nitrogen depletion was studied using 2-DE.In addition,we identified six differentially expressed proteins whose relative abundance increased or decreased more than 1.5-fold(Preduced,which may decrease the DNA replication level and ATP production in P.globosa cells.The increase of endonucleaseⅢand transcriptional regulator enzyme may affect the metabolic and antioxidant function of P.globosa cells and induce cell apoptosis.These findings provide a basis for further proteomic study of P.globosa and the optimization of protein preparation methods of marine microalgae.

关键词： Phaeocystis globosa nitrogen limitation proteomic response two-dimensional electrophoresis

Defined hydrogels for spinal cord organoids:challenges and potential applications

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Neural Regeneration Research 2024年第11期19卷 2329-2330页

作者： Wai Hon Chooi Yuewen Wu Shi-Yan Ng Institute of Molecular and cell Biology(IMCB) Agency for ScienceTechnology and Research(A*STAR)SingaporeSingapore Department of physiology Yong Loo Lin School of MedicineNational University of Singapore(NUS)SingaporeSingapore

Organoids of the central nervous system,primarily derived from pluripotent stem cells or neural stem cells,are three-dimensional tissue cultures with self-organizing properties.When exposed to the right combinations of signals,they differentiate into a 3D tissue consisting of complex cytoarchitecture and native cell types,including various neuron subtypes and glial cells.These features closely mimic native tissues,making them invaluable for developmental studies and disease modeling.In recent years,spinal cord organoids(SCOs)have been developed to investigate spinal cord development,injuries,and various neurological disorders.As an integral part of the central nervous system,SCOs play a vital role and serve as a site for studying both neurodevelopment and neurodegenerative diseases.

关键词： properties injuries primarily

Bioengineered skin organoids:from development to applications

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Military Medical Research 2024年第3期11卷 449-466页

作者： Zi-Xuan Hong Shun-Tian Zhu Hao Li Jing-Zhi Luo Yu Yang Yang An Xi Wang Kai Wang Department of physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China Department of Hepatopancreatobiliary Surgery the Third Affiliated Hospital of Soochow UniversityChangzhou 213000JiangsuChina Department of Plastic Surgery Peking University Third HospitalBeijing 100191China Clinical Stem cell Research Center Peking University Third HospitalBeijing 100191China State Key laboratory of Cardiovascular Disease Fuwai HospitalBeijing 100037China Beijing Key laboratory of Metabolic Disorder Related Cardiovascular Disease Capital Medical UniversityBeijing 100050China

Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids.Serving as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional(2D)systems and ethical concerns.The inherent plasticity of skin organoids allows for their construction into physiological and pathological models,enabling the study of skin development and dynamic changes.This review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with appendages.Furthermore,it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques,such as 3D printing and microfuidic devices.The review also summarizes and discusses the diverse applications of skin organoids in developmental biology,disease modelling,regenerative medicine,and personalized medicine,while considering their prospects and limitations.

关键词： Skin organoid Organoid generation Skin appendage Tissue engineering Disease modelling Regenerative medicine

Masculinizer gene controls sexual differentiation in Hyphantria cunea

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Insect Science 2024年第2期31卷 405-416页

作者： Xiaowei Li Huihui Liu Honglun Bi Yaohui Wang Jun Xu Sufang Zhang Zhen Zhang Ze Zhang Yongping Huang laboratory of Evolutionary and Functional Genomics School of Life SciencesChongqing UniversityChongqingChina CAS Key laboratory of Insect Developmental and Evolutionary Biology CAS Centerfor Excellence in Molecular Plant SciencesInstitute of Plant Physiology and EcologyShanghaiChina Key laboratory of Forest Protection Research Institute of Forest EcologyEnvironment and ProtectionChinese Academy of ForestryState Forestry AdministrationBeijingChina

The Masculinizer gene,Masc,encodes a lepidopteran-specific novel CCCHtype zinc finger protein,which controls sex determination and dosage compensation in Bombyx mori.Considering the potential application of it in pest control,it is necessary to investigate the function of Masc gene in Hyphantria cunea,a globally invasive forest pest.In the present study,we identified and functionally characterized the Masc gene,HcMasc,in H.cunea.Sequence analysis revealed that HcMASC contained the conserved CCCH-type zinc finger domain,nuclear localization signal,and male determining domain,in which the last was confirmed to be required for its masculinization in BmN cell line.However,expression data showed that unlike male-biased expression in B.mori,Hc-Masc gene expresses in main all developmental stages or tissues in both sexes.Clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated protein 9-based disruption of the common exons 1 and 3 of the HcMasc gene resulted in imbalanced sex ratio and abnormal external genitalia of both sexes.Our results suggest that the HcMasc gene is required for both male and female sexual differentiation and dosage compensation in H.cunea and provide a foundation for developing better strategies to control this pest.

关键词： CRISPR/Cas9 dosage compensation Hyphantria cunea Masc sexual differentiation