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

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 ***-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain ***-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 *** glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous *** brain insult,microglia are the first cells to respond,followed by reactive *** activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the ***,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many *** 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 *** 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 *** 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,Parkins

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

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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 *** studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s *** 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 ***,ethical issues and tumor formation were limitations of its clinical *** pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell *** 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 *** induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s ***,there are also ethical concerns and the risk of tumor formation that need to be *** 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 *** 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 *** 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

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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 *** folate supplementation has been shown to mitigate the incidence of NTDs,some cases,often attributable to genetic factors,remain *** SHROOM3 gene has been implicated in NTD cases that are unresponsive to folate supplementation;at present,however,the underlying mechanism remains *** tube morphogenesis is a complex process involving the folding of the planar epithelium of the neural *** 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 *** of SHROOM3 resulted in shorter neuroepithelial cells and smaller *** 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 ***,these defects were not rescued by folate *** sequencing revealed that differentially expressed genes were enriched in biological processes associated with cellular and organ *** 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

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COVID-19 vaccines and beyond

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cellular & Molecular Immunology 2024年第3期21卷 207-209页

作者： Yiyuan Liu Danying Li Jiahuai Han State Key laboratory of cellular Stress Biology Innovation Center for Cell BiologySchool of Life SciencesXiamen UniversityXiamenFujianChina laboratory animal Center Xiamen UniversityXiamenFujianChina research unit of cellular Stress of CAMS Cancer Research Center of Xiamen UniversityXiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenFujianChina

Hundreds of vaccines have been developed worldwide for Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the cause of Coronavirus disease 2019(COVID-19),since the beginning of the *** vaccines have saved innumerable lives and contributed to partial control of the COVID-19 *** of the vaccines approved for clinical use exhibit satisfactory initial protection rates against corresponding ***,vaccine protection declines over time,with almost all vaccines falling below 50%protection after 6 months[1].In the case of natural infections,protection lasts longer,but the incidence of reinfection is also quite high.

关键词： vaccines acute beyond

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Improve meat production and virus resistance by simultaneously editing multiple genes in livestock using Cas12i^(Max)

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Science China(Life Sciences) 2024年第3期67卷 555-564页

作者： Jilong Ren Tang Hai Yangcan Chen Ke Sun Zhiqiang Han Jing Wang Chongyang Li Qingwei Wang Leyun Wang Huabing Zhu Dawei Yu Wei Li Shanjiang Zhao State Key laboratory of animal Nutrition Key Laboratory of Animal GeneticsBreeding and Reproduction of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijing 100193China State Key laboratoryf Stem cell and Reproductive Biology Instituteof ZooogyChinese Academyof SciencesBeijing 100101China Beijing Institute for Stem cell and Regenerative Medicine Beijing 100101China Beijing Farm animal research Center Institute of ZoologyChinese Academy of SciencesBeijing 100101China

The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated gene(Cas) system is continually optimized to achieve the most efficient gene editing effect. The Cas12i^(Max), a Cas12i variant, exhibits powerful DNA editing activity and enriches the gene editing toolbox. However, the application of Cas12i^(Max)in large domestic animals has not yet been reported. To verify the efficiency and feasibility of multiple gene editing in large animals, we generated porcine fibroblasts with simultaneous knockouts of IGF2, ANPEP, CD163,and MSTN via Cas12i^(Max)in one step. Phenotypically stable pigs were created through somatic cell nuclear transfer technology. They exhibited improved growth performance and muscle quality. Furthermore, we simultaneously edited three genes in bovine fibroblasts. A knockout of MSTN and PRNP was created and the amino acid Q-G in CD18 was precisely substituted. Meanwhile, no off-target phenomenon was observed by sum-type analysis or off-target detection. These results verified the effectiveness of Cas12i^(Max)for gene editing in livestock animals and demonstrated the potential application of Cas12i^(Max)in the field of animal trait improvement for agricultural production.

关键词： Cas12i^(Max) gene editing livestock multiple trait improvement

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Long-term in vivo chimeric cells tracking in non-human primate

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Protein & cell 2024年第3期15卷 207-222页

作者： Junmo Wu Yu Kang Xiang Luo Shaoxing Dai Yuxi Shi Zhuoyao Li Zengli Tang Zhenzhen Chen Ran Zhu Pengpeng Yang Zifan Li Hong Wang Xinglong Chen Ziyi Zhao Weizhi ji Yuyu Niu State Key laboratory of Primate biomedical research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunming 650500China Yunnan Key laboratory of Primate biomedical research Kunming 650500China Faculty of Life Science and Technology Kunming University of Science and TechnologyKunming 650500China

Non-human primates(NHPs)are increasingly used in preclinical trials to test the safety and efficacy of biotech-nology ***,given the ethical issues and costs associated with this model,it would be highly advantageous to use NHP cellular models in clinical ***,developing and maintaining the naive state of primate pluripotent stem cells(PSCs)remains difficult as does in vivo detection of PSCs,thus limiting biotech-nology application in the cynomolgus ***,we report a chemically defined,xeno-free culture system for culturing and deriving monkey PSCs in *** cells display global gene expression and genome-wide hypometh-ylation patterns distinct from monkey-primed *** also found expression of signaling pathways components that may increase the potential for chimera *** for biomedical applications,we were also able to integrate bioluminescent reporter genes into monkey PsCs and track them in chimeric embryos in vivo and in *** engineered cells retained embryonic and extra-embryonic developmental ***,we generated a chimeric monkey carrying bioluminescent cells,which were able to track chimeric cells for more than 2 years in living *** study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models forclinical studies.

关键词： pluripotent stem cells bioluminescence imaging non-human primates

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Hematopoietic aging:cellular,molecular,and related mechanisms

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Chinese Medical Journal 2024年第11期137卷 1303-1312页

作者： Li Ye Chuan Tian Ye Li Hang Pan Jinxiu Hu Liping Shu Xinghua Pan The Stem cells and Immune cells biomedical Techniques Integrated Engineering laboratory of State and Regions Cell Therapy Technology Transfer Medical Key Laboratory of Yunnan ProvinceKunming Key Laboratory of Stem Cell and Regenerative MedicineBasic Medical Laboratory920th Hospital of Joint Logistics Support ForcePLAKunmingYunnan 650032China Department of Immunology of School of Basic Medicine of Guizhou Medical University National and Local Joint Engineering Laboratory of Cell Engineering Biomedical TechnologyKey Laboratory of Regenerative Medicine of Guizhou ProvinceState Key Laboratory of Efficacy and Utilization of Medicinal Plants Co-constructed by Province and MinistryKey Laboratory of Translational Research of Adult Stem Cell of Chinese Academy of Medical SciencesGuiyangGuizhou 550025China

Aging is accompanied by significant inhibition of hematopoietic and immune system function and disruption of bone marrow ***-related alterations in the inflammatory response,immunity,and stem cell niches are at the root of hematopoietic *** the molecular mechanisms underlying hematopoietic and bone marrow aging can aid the clinical treatment of aging-related *** particular,it is unknown how the niche reprograms hematopoietic stem cells(HSCs)in an age-dependent manner to maintain normal hematopoiesis in elderly ***,specific inhibitors and blood exchange methods have been shown to reshape the hematopoietic niche and reverse hematopoietic ***,we present the latest scientific discoveries related to hematopoietic aging and hematopoietic system rejuvenation,discuss the relationships between hematopoietic niche aging and HSC aging,and describe related studies on stem cell-mediated regulation of hematopoietic aging,aiming to provide new ideas for further study.

关键词： Stem cells Hematopoietic stem cell Niche Hematopoietic aging

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Nanomedicine-mediated immunogenic cell death and its combination with immune checkpoint blockade therapy

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Science China(Technological Sciences) 2024年第8期67卷 2350-2362页

作者： CHEN JunBin ZHANG YuXi SU Miao ZHU YueQiang YANG XianZhu School of biomedical Sciences and Engineering South China University of TechnologyGuangzhou International CampusGuangzhou 511442China National Engineering research Center for Tissue Restoration and Reconstruction Guangdong Provincial Key Laboratory of Biomedical EngineeringKey Laboratory of Biomedical Materials and Engineering of the Ministry of EducationSouth China University of TechnologyGuangzhou 510006China

Cancer immunotherapies, which train the natural immune system to specifically kill tumor cells while sparing the healthy cells,have helped revolutionize cancer treatments and demonstrated promising clinical therapeutic benefits for decades. However, the therapeutic outcome of immunotherapies, even for the most successful immune checkpoint blockade(ICB) therapy, remains unsatisfactory in the clinical practice, mainly due to the low immunogenicity of solid tumors and its immunosuppressive tumor microenvironment(TME). Notably, several cancer treatment modalities, including chemotherapy, radiotherapy, and phototherapy, have been revealed to evoke tumor immunogenicity and reverse immunosuppressive TME via inducing immunogenic cell death(ICD) of tumor cells, which synergistically sensitized tumors to ICB therapy. Nanomedicines have been extensively applied to augment ICD-inducing treatment modalities and potentiate ICB therapeutic efficacy therapy due to the opportune convergence of immunotherapy and nanotechnology. Here, we discuss the recent advances in nanomedicine-mediated ICD and its combination with ICB therapy.

关键词： cancer immunotherapy nanomedicine immunogenic cell death immune checkpoint blockade

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Harnessing cytokine-induced killer cells to accelerate diabetic wound healing:an approach to regulating post-traumatic inflammation

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Regenerative Biomaterials 2024年第2期3卷 88-99页

作者： Yixi Yang Cheng Zhang Yuan Jiang Yijun He iawei Cai Lin Liang Zhaohuan Chen Sicheng Pan Chu Hua Keke Wu Le Wang Zhiyong Zhang Translational research centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University Guangdong Province Engineering Research Center for Biomedical EngineeringState Key Laboratory of Respiratory DiseaseDepartment of Orthopaedic SurgeryMedical Technology and Related Equipment Research for Spinal Injury TreatmentCity Key LaboratoryThe Third Affliated Hospital of Guangzhou Medical UniversitySchool of Biomedical EngineeringGuangzhou MedicalUniversityGuangzhouGuangdong510150P.R.China Department of Osteoarthropathy and Sports Medicine Panyu Central HospitalGuangzhou 511400P.R.China

Impaired immunohomeostasis in diabetic wounds prolongs infiammation and cytokine dysfunction,thus,delaying or pre-venting wound-surface *** clinical studies have been conducted on cytokine-induced killer(CIK)cells recently,as they can be easily proliferated using a straightforward,inex-pensive ***,the function of CIK cells in regulat-ing inflammatory environments has been drawing attention for clinical *** the current investigation,we discovered the regenerative capacity of these cells in the chal-lenging environment of wounds that heal poorly due to *** demonstrated that the intravenous injection of CIK cells can re-establish a proregenerative inflammatory *** *** accelerateskin healing in diabetic *** results indicated that CIK cell treatment affects macrophage polarization and restores the function regenerative cells under hyperglycemic *** novel cellular therapy offers a promising intervention for clinical applic tions through specific inflammatory regulation functions.

关键词： macrophage diabetic wound post-traumatic inflammation cytokine-induced killer cells vascularization

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Current perspectives on mesenchymal stem cells as a potential therapeutic strategy for non-alcoholic fatty liver disease

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World Journal of Stem cells 2024年第7期16卷 760-772页

作者： Yan Jiang Narazah Mohd Yusoff Jiang Du Emmanuel Jairaj Moses Jun-Tang Lin School of Nursing Xinxiang Medical UniversityXinxiang 453000Henan ProvinceChina Department of biomedical Sciences Advanced Medical and Dental InstituteUniversiti Sains MalaysiaKepala Batas 13200Pulau PinangMalaysia Advanced Medical and dental Institute Universiti Sains MalaysiaKepala Batas 13200Pulau PinangMalaysia Henan Joint International research laboratory of Stem cell Medicine School of Medical EngineeringXinxiang Medical UniversityXinxiang 453003Henan ProvinceChina Stem cells and Biotherapy Engineering research Center of Henan National Joint Engineering Laboratory of Stem Cells and BiotherapySchool of Life Science and TechnologyXinxiang Medical UniversityXinxiang 453003Henan ProvinceChina Henan Joint International research laboratory of Stem cell Medicine School of Medical EngineeringXinxiang Medical UniversityXinxiang 453000Henan ProvinceChina

Non-alcoholic fatty liver disease(NAFLD)has emerged as a significant health challenge,characterized by its widespread prevalence,intricate natural progression and multifaceted *** NAFLD initially presents as benign fat accumulation,it may progress to steatosis,non-alcoholic steatohepatitis,cirrhosis,and hepatocellular *** stem cells(MSCs)are recognized for their intrinsic self-renewal,superior biocompatibility,and minimal immunogenicity,positioning them as a therapeutic innovation for liver ***,this review aims to elucidate the potential roles of MSCs in alleviating the progression of NAFLD by alteration of underlying molecular pathways,including glycolipid metabolism,inflammation,oxidative stress,endoplasmic reticulum stress,and *** insights are expected to provide further understanding of the potential of MSCs in NAFLD therapeutics,and support the development of MSC-based therapy in the treatment of NAFLD.

关键词： Non-alcoholic induced fatty liver disease Mesenchymal stem cells Lipid accumulation Inflammation Oxidative stress Endoplasmic reticulum stress Fibrosis

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