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Cell reprogramming therapy for Parkinson’s disease

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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Photocatalytic activation of sulfite by N-doped porous biochar/MnFe_(2)O_(4) interface-driven catalyst for efficient degradation of tetracycline

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Green Energy & Environment 2024年第3期9卷 481-494页

作者： Long Cheng Yuanhui Ji Jiangsu Province Hi-Tech Key laboratory for biomedical research School of Chemistry and Chemical EngineeringSoutheast UniversityNanjing211189China

A novel photo-catalytic system composed of N-doped biochars(NBCs),MnFe_(2)O_(4) and sulfite activation under ultraviolet(NBCs/MnFe_(2)O_(4)/sulfite/UV)was constructed to realize the efficient eliminate of tetracycline(TC).As the carrier of MnFe_(2)O_(4),NBCs were synthesized from alfalfa,which has large specific surface area,graphite like structure and hierarchical porous *** adsorption isotherm indicated that NBCs/MnFe_(2)O_(4)-2:1 had the best adsorption performance for TC(347.56 mg g^(-1)).Through synergistic adsorption and photocatalysis,the removal rate of TC reached 84%,which was significantly higher than that of MnFe_(2)O_(4).Electrochemical impedance spectroscopy(EIS)and Photoluminescence(PL)characterization results showed that the introduction of NBCs improved the separation efficiency of photogenerated electron and hole pairs and enhanced the photocatalytic ***,the adsorption,degradation mechanism and degradation path of TC by the catalyst were systematically analyzed by coupling HPLC–MS measurement with the theoretical *** the advantages of excellent degradation performance,low cost,easy separation and environmental friendliness of NBCs/MnFe_(2)O_(4),this work was expected to provide a new path for the practical application of biochar.

关键词： Biochar MnFe_(2)O_(4) Sulfite Adsorption Photocatalysis

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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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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 ***-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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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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Machine learning with active pharmaceutical ingredient/polymer interaction mechanism:Prediction for complex phase behaviors of pharmaceuticals and formulations

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Chinese Journal of Chemical Engineering 2024年第2期66卷 263-272页

作者： Kai Ge Yiping Huang Yuanhui Ji Jiangsu Province Hi-Tech Key laboratory for biomedical research School of Chemistry and Chemical EngineeringSoutheast UniversityNanjing 211189China

The high throughput prediction of the thermodynamic phase behavior of active pharmaceutical ingredients(APIs)with pharmaceutically relevant excipients remains a major scientific challenge in the screening of pharmaceutical *** this work,a developed machine-learning model efficiently predicts the solubility of APIs in polymers by learning the phase equilibrium principle and using a few molecular *** the few-shot learning framework,thermodynamic theory(perturbed-chain statistical associating fluid theory)was used for data augmentation,and computational chemistry was applied for molecular descriptors'*** results showed that the developed machine-learning model can predict the API-polymer phase diagram accurately,broaden the solubility data of APIs in polymers,and reproduce the relationship between API solubility and the interaction mechanisms between API and polymer successfully,which provided efficient guidance for the development of pharmaceutical formulations.

关键词： Multi-task machine learning Density functional theory Hydrogen bond interaction Miscibility Solubility

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Bioinspired design of integral molded Janus silk fibroin-MXene evaporator for efficient solar vapor generation

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Nano research 2024年第4期17卷 2824-2835页

作者： Ling-Qing Kong Zhi-Cheng Zeng Guang-Zong Min Zhao-Hui Meng Guo-Qing Meng Xiao-Xiao Guo Nai-Bo Lin Xiang-Yang Liu The Higher Educational Key laboratory for biomedical Engineering of Fujian Province Research Center of Biomedical Engineering of XiamenDepartment of BiomaterialsCollege of MaterialsXiamen UniversityXiamen 361005China The State Key laboratory of Marine Environmental Science(MEL) College of Ocean and Earth SciencesXiamen UniversityXiamen 361005China

Solar vapor generation is a promising sustainable technology that uses solar distillation to produce fresh water from seawater and wastewater,helping relieve global water resource ***,inspired by naturally grown integrally molded mulberry leaves with a Janus hydrophilic and hydrophobic structure,a novel,simple,and efficient integrated molding method is proposed to break through the limitations of the traditional split manufacturing strategy and realizes the integrated formation of Janus *** on the spontaneous sedimentation characteristics of MXene in silk fibroin solution and its regulation of mesoscopic structure and hydrophilicity of silk fibroin,layered structures with different compositions and hydrophilicities were obtained in one ***,ethanol and glutaraldehyde were added to construct a physical crystallization-chemical crosslinking dual stabilization structure in silk *** evaporator has the evaporation rate of 3.07 kg·m^(-2)·h^(-1) and the efficiency of 86.8%under 1 sun and maintains high evaporation performance under various extreme test conditions including vigorous washing,repeated compression,and high-intensity ultraviolet(UV)***,the evaporator performs well in practical application scenarios,its evaporation rate in the simulated Dead Sea seawater exceeds 2.13 kg·m^(-2)·h^(-1),and more than 99.9%of the salt,heavy metal ions,oil pollution,and dyes are purified.

关键词： silk fibroin MXene bioinspired integrated molding Janus structure solar vapor generation

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Tumor microenvironment-activatable neuropeptide-drug conjugates enhanced tumor penetration and inhibition via multiple delivery pathways and calcium deposition

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Chinese Chemical Letters 2024年第4期35卷 292-297页

作者： Yi Cao Xiaojiao Ge Yuanyuan Wei Lulu He Aiguo Wu Juan Li Ningbo Key laboratory of biomedical Imaging Probe Materials and Technology Zhejiang International Cooperation Base of Biomedical Materials Technology and ApplicationChinese Academy of Sciences(CAS)Key Laboratory of Magnetic Materials and DevicesNingbo Cixi Institute of Biomedical EngineeringZhejiang Engineering Research Center for Biomedical MaterialsNingbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingbo 315201China University of Chinese Academy of Sciences Beijing 100049China Advanced Energy Science and Technology Guangdong laboratory Huizhou 516000China

Peptide-drug conjugates have achieved considerable development and application as a novel strategy for targeted delivery of anticancer drugs. Bioactive peptides induced calcium deposition can irreversibly assist inhibition of tumors. However, active regulation of calcium level through signal transduction of bioactive substances has not been reported yet. In this study, novel neuropeptide-doxorubicin conjugates(NP-DOX) with lysosome-specific acid response were described for neuropeptide Y_1 receptor(Y_1R)-overexpressed triple-negative breast cancer. The delivery mechanism of NP-DOX was clarified that diverse pathways were involved, including intracellular and intercellular transport. Importantly, up-regulation of Y_1 R-mediated intracellular calcium level via second messenger inositol triphosphate was presented in NP-DOX treated MDA-MB-231 cells. In vivo antitumor efficacy demonstrated that NP-DOX showed less organ toxicity and enhanced tumor inhibition benefited from its controlled release and Y_1R-mediated calcium deposition, compared with free DOX. This bioconjugate is a proof-of-concept confirming that neuropeptide-mediated control of signaling responses in neuropeptide-drug conjugates enables great potential for further applications in tumor chemotherapy.

关键词： Neuropeptide-drug conjugate Tumor penetration Calcium deposition Tumor inhibition Triple-negative breast cancer

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Tailoring sulfur-doped and nitrogen-defective carbon nitride nanosheets for efficient photo-controlled radical polymerizations

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Science China Chemistry 2024年第7期67卷 2325-2334页

作者： Xue Li Meng Kai Xu Yuan Huang Tao Cai Key laboratory of biomedical Polymers of Ministry of Education College of Chemistry and Molecular SciencesWuhan UniversityWuhan 430072China Wuhan University Shenzhen research Institute Shenzhen 518057China

Despite the challenges that remain,the synergistic adjustment of various microstructures and photochemical parameters of graphitic carbon nitride(g-C_(3)N_(4))in photocatalytic reactions holds promises for improving catalytic efficiency and reducing energy ***,sulfur-doped and nitrogen-defective g-C_(3)N_(4)(n-SC_(3)N_(x))nanosheets were designed and elaborately *** resultant n-SC_(3)N_(x)possessed a precisely defined 2D layer structure with extensive porosity and incremental specific surface *** photoinduced electron transfer-reversible addition-fragmentation chain transfer(PET-RAFT)polymerization of vinyl monomers with low dispersity,excellent temporal control and high chain-end fidelity was achieved under mild blue light irradiation in a nondegassed *** to their ultrathin nanostructures with nitrogen defects and sulfur dopants,n-SC_(3)N_(x)was capable of catalyzing RAFT polymerization in aqueous solutions at significantly accelerated rates,which were nearly 8 times faster compared to bulk g-C_(3)N_(4).The ease of separation and efficient reusability in subsequent polymerizations was enabled by the heterogeneous nature of n-SC_(3)N_(x).The appeal of this approach was illustrated by the fact that utilizing a reusable and metal-free photocatalyst in aqueous environments allowed for the synthesis of polymers with molecular weight up to 300 kg mol^(-1) and a dispersity of 1.32.

关键词： graphitic carbon nitride nitrogen defects sulfur dopants PET-RAFT polymerization recyclability

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