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Ptip safeguards the epigenetic control of skeletal stem cell quiescence and potency in skeletogenesis

Science Bulletin 2024年第13期69卷 2099-2113页

作者： Jianfei Liang Jing Wang Bingdong Sui Yibo Tong Jihua Chai Qin Zhou Chenxi Zheng Hao Wang Liang Kong Haojian Zhang Yi Bai state key laboratory of Oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyTaikang Center for Life and Medical SciencesWuhan UniversityWuhan 430079China key laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi’an Jiaotong UniversityXi’an 710004China Department of Implant Dentistry College of StomatologyXi’an Jiaotong UniversityXi’an 710004China state key laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Key Laboratory of StomatologyShaanxi International Joint Research Center for Oral DiseasesCenter for Tissue EngineeringSchool of StomatologyThe Fourth Military Medical UniversityXi’an 710032China state key laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China state key laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Key Laboratory of StomatologyDepartment of Oral and Maxillofacial SurgerySchool of StomatologyThe Fourth Military Medical UniversityXi’an 710032China Department of Hematology Zhongnan HospitalWuhan UniversityWuhan 430079China Frontier Science Center for Immunology and Metabolism Medical Research InstituteWuhan UniversityWuhan 430079China Taikang Center for life and Medical sciences Wuhan UniversityWuhan 430079China

Stem cells remain in a quiescent state for long-term maintenance and preservation of potency;this process requires fine-tuning regulatory *** this study,we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells(SSCs)in skeletogenesis governed by a key regulator,Ptip(also known as Paxip1,Pax interaction with transcription-activation domain protein-1).Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs,and loss of Ptip in type II collagen(Col2)^(+)progenitors causes abnormal activation and differentiation of SSCs,impaired growth plate morphogenesis,and long bone *** also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1(Pgk1)by repressing histone H3 lysine 27 acetylation(H3K27ac)at the promoter ***,inhibition of glycolysis improved the function of SSCs despite Ptip *** the best of our knowledge,this is the first study to establish an epigenetic framework based on Ptip,which safeguards skeletal stem cell quiescence and potency through metabolic *** framework is expected to improve SSC-based treatments of bone developmental disorders.

关键词： Skeletal stem cells Bone development Epigenetics Ptip Glycolysis

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Food-derived bio-functional peptides for the management of hyperuricemia and associated mechanism

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Food Science and Human Wellness 2024年第4期13卷 1767-1786页

作者： Yanxin Wang Mingxia Ma Yumeng Huang Siqing Fan Jie Peng Shiming Li Xiurong Su Yanbo Wang Chenyang Lu state key laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products and school of Marine Science Ningbo UniversityNingbo 315211China school of Food and Health Beijing Technology and Business UniversityBeijing 100048China Department of Food Science Rutgers UniversityNew BrunswickNJ 08901USA College of life sciences Huanggang Normal UniversityHuanggang 438000China Food Safety key laboratory of Zhejiang Province School of Food Science and BiotechnologyZhejiang Gongshang UniversityHangzhou 310018China

Hyperuricemia,a metabolic disorder related to uric acid metabolism dysregulation,has become a common metabolic disease worldwide,due to changes in lifestyle and dietary *** recent years,owing to their high activity and few adverse effects,food-derived active peptides used as functional foods against hyperuricemia have attracted increasing *** article aims to focus on the challenge associated with peptide-specific preparation methods development,functional components identification,action mechanism(s)clarification,and bioavailability *** current review proposed recent advances in producing the food-derived peptides with high anti-hyperuricemia activity by protein source screening and matched enzymatic hydrolysis condition adjusting,increased the knowledge about strategies to search antihyperuricemia peptides with definite structure,and emphasized the necessity of combining computer-aided approaches and activity *** addition,novel action mechanism mediated by gut microbiota was discussed,providing different insights from classical ***,considering that little attention was paid previously on the structure-activity relationships of anti-hyperuricemia peptides,we collected the sequences from published studies and make a preliminary summary about the structure-activity relationships,which in turn provided guides for enzymatic hydrolysis optimization and bioavailability ***,this article could promote the development,application and commercialization of food-derived anti-hyperuricemia peptides in the future.

关键词： Hyperuricemia Peptide Enzyme hydrolysis Mechanism Structure-activity relationship Bioavailability

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Combination strategies for first-line treatment of patients with unresectable hepatocellular carcinoma:prospect of natural products

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Chinese Journal of Natural Medicines 2024年第1期22卷 1-3页

作者： ZHANG Lele LU Jinjian school of Basic Medical sciences Chengdu UniversityChengdu 610106China state key laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China Department of pharmaceutical sciences Faculty of Health SciencesUniversity of MacaoMacao 999078China

Liver cancer stands as a significant global health concern,contributing substantially to cancer incidence and mortality,particularly in Asian countries[1].Hepatocellular carcinoma(HCC)accounts for approximately 90%of all liver cancer cases and is characterized by a high-risk profile and a generally poor prognosis[2].To address advanced HCC,systemic therapy has been recommended,leading to the approval of a range of treatment regimens in clinical ***,first-line therapy involved the use of multitargeted tyrosine kinase inhibitors(TKIs)such as sorafenib or lenvatinib,while cabozantinib,ramucirumab.

关键词： Unresectable hepatocellular carcinoma Combination strategies Immunotherapy PD-1/PD-L1 Natural products

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Transferrin receptor-targeted immunostimulant for photodynamic immunotherapy against metastatic tumors through b-catenin/CREB interruption

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4118-4133页

作者： Mengyi Yan Xiayun Chen Xiaotong Li Qianqian Liu Baixue Yu Yi Cen Wei Zhang Yibin Liu Xinxuan Li Ying Chen Tao Wang Shiying Li The Fifth Affiliated Hospital Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacologythe NMPA and State Key Laboratory of Respiratory Diseasethe School of Pharmaceutical SciencesGuangzhou Medical UniversityGuangzhou 511436China Department of Anesthesiology the Second Clinical School of Guangzhou Medical UniversityGuangzhou 511436China state key laboratory of Respiratory Diseases Guangdong Key Laboratory of Vascular DiseasesGuangzhou Institute of Respiratory Healththe first Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510120China Department of Pulmonary and Critical Care Medicine Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China

The immunosuppressive phenotype of tumor cells extensively attenuates the immune activation effects of traditional *** this work,a transferrin receptor(TfR)targeted immunostimulant(PTI)is fabricated for photodynamic immunotherapy against metastatic tumors by interrupting b-catenin signal *** synthesize PTI,the photosensitizer conjugated TfR targeting peptide moiety(Palmitic-K(PpIX)-HAIYPRH)is unitized to encapsulate the transcription interrupter of *** the one hand,the recognition of PTI and TfR can promote drug delivery into tumor cells to destruct primary tumors through photodynamic therapy and initiate an immunogenic cell death with the release of tumorassociated *** the other hand,PTI will interrupt the binding between b-catenin andcAMP response element-binding protein(CREB),regulating the gene transcription to downregulate programmed death ligand 1(PD-L1)while upregulating CeC motif chemokine ligand 4(CCL4).Furthermore,the elevated CCL4 can recruit the dendritic cells to present tumor-specific antigens and promote T cells activation and infiltration,and the downregulated PD-L1 can avoid the immune evasion of tumor cells and activate systemic anti-tumor immunity to eradicate lung *** work may inspire the development of antibody antibody-free strategy to activate systemic immune response in consideration of immunosuppressive conditions.

关键词： Transferrin receptor b-Catenin signal pathway Tumor targeting Photodynamic therapy Immunotherapy Immunogenic cell death Programmed death ligand 1

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Distinct Effects of Three Tea Varieties Made Green Teas on Improving Diabetic Dyslipidemia Induced by High-Fat Diet in C57BL/6J Mice

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Food Science and Human Wellness 2024年

作者： Wei Gu Zhutong Wang Guohuo Wu Huimin Guo Huijun Cheng Cong Li Linbo Chen Daxiang Li Zhongwen Xie state key laboratory of Tea Plant Biology and Utilization， school of Tea and Food sciences & Technology， Anhui Agricultural University Center for biotechnology， Anhui Agricultural University College of life sciences， Anhui Agricultural University Tea Research Institute， Yunnan Academy of Agricultural sciences

Currently， cultivated tea plants are classified into three varieties， namely， C. sinensis var. sinensis， C. sinensis var. assamica， and C. sinensis var. kucha. Three tea varieties made green teas (TVGTs) are widely consumed worldwide. However， a comparative investigation of the beneficial effects， mechanism， and characteristic compounds of TVGTs has not been reported. Here， three representative tea plant varieties， namely， C. sinensis var. sinensis cv. Fuding (FD)， C. sinensis var. assamica cv. Yunkang 10 (YK)， and C. sinensis var. kucha (KC)， planted in the same garden， were used to make green teas utilizing the same standard procedure. Our findings show that the TVGTs effectively improved hyperglycemia， obesity， dyslipidemia， fatty liver， and mesenteric artery (MA) hypercontractility in mice with diabetes and obesity induced by a high-fat diet (HFD) after 11- and 22-week interventions， with YK being the most effective at 22 weeks. Liver lipidomics indicated that the TVGTs restored the glycerophospholipid and sphingolipid balance and reduced triglycerides， with YK demonstrating superior effects. The TVGTs， particularly YK， suppressed triglyceride synthesis through the ARV1-FXR-SHP-SREBP-1c pathway. A chemical profile analysis revealed that YK green tea had enriched active compounds， including caffeine， quinic acid， L-theanine， gallic acid， and catechins， compared with FD and KC green teas， which may contribute to ameliorating diabetic dyslipidemia via synergistic action. As a representative tea variety of C. sinensis var. assamica， YK green tea was found to be superior to the other two green teas in preventing and treating diabetic dyslipidemia， especially with long-term consumption. These data provide important information for tea plant breeders and tea consumers.

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Installing hydrogen bonds as a general strategy to control viscosity sensitivity of molecular rotor fluorophores Special Collection:Aggregation-Induced Processes and Functions

Aggregate

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Aggregate 2024年第1期5卷 367-376页

作者： Baoxing Shen Lihua Liu Yubo Huang Jichun Wu Huan Feng Yu Liu He Huang Xin Zhang Department of Chemistry Research Center for Industries of the FutureWestlake UniversityHangzhouChina Westlake laboratory of life sciences and Biomedicine HangzhouChina school of Food Science and pharmaceutical Engineering Nanjing Normal UniversityNanjingChina CAS key laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalianChina

Molecular rotor-based fluorophores(RBFs)activate fluorescence upon increase of micro-viscosity,thus bearing a broad application promise in many ***,it remains a challenge to control how fluorescence of RBFs responds to viscosity ***,we demonstrate that the formation and regulation of intramolecular hydrogen bonds in the excited state of RBFs could modulate their rotational barrier,leading to a rational control of how their fluorescence can be activated by *** on this strategy,a series of RBFs were developed based on 4-hydroxybenzylidene-imidazolinone(HBI)that span a wide range of viscosity *** with the AggTag method that we previously reported,the varying viscosity sensitivity and emission spectra of these probes enabled a dualcolor imaging strategy that detects both protein oligomers and aggregates during the multistep aggregation process of proteins in live *** summary,our work indicates that installing intracellular excited state hydrogen bonds to RBFs allows for a rational control of rotational barrier,thus allow for a fine tune of their viscosity *** RBFs,we envision similar strategies can be applied to control the fluorogenic behavior of a large group of fluorophores whose emission is dependent on excited state rotational motion,including aggregation-induced emission fluorophores.

关键词： fluorescent probe intramolecular hydrogen bond protein aggregation rotor-based fluorophores viscosity sensitivity

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Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling

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Journal of pharmaceutical Analysis 2024年第4期14卷 601-614页

作者： Bei Li Yong Zhang Xinyuan Liu Ziyang Zhang Shuqing Zhuang Xiaoli Zhong Wenbo Chen Yilin Hong Pingli Mo Shuhai Lin Shicong Wang Chundong Yu state key laboratory of Cellular Stress Biology School of Life SciencesXiamen UniversityXiamen361102China Fujian Pien Tze Huang Enterprise key laboratory of Natural Medicine Research and Development ZhangzhouFujian363000China Xiang'an Hospital of Xiamen University School of MedicineXiamen UniversityXiamen361005China Department of Cardiology Xiamen Key Laboratory of Cardiac ElectrophysiologyXiamen Institute of Cardiovascular DiseasesThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen361003China

Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is ***,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)***,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK *** of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating ***,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory ***,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

关键词： Pien Tze Huang Bile acids Sepsis Inflammation TGR5 STAT3-A20 signalling

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Engineered extracellular vesicles efficiently deliver CRISPR-Cas9 ribonucleoprotein(RNP)to inhibit herpes simplex virus1 infection in vitro and in vivo

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1362-1379页

作者： Yuanda Wan Liren Li Ruilin Chen Jiajia Han Qiyun Lei Zhipeng Chen Xiaodong Tang Wenyu Wu Shuwen Liu Xingang Yao NMPA key laboratory for Research and Evaluation of Drug Metabolism Guangdong Provincial Key Laboratory of New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Center of Clinical Pharmacy Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China state key laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China key laboratory of Infectious Diseases Research in South China(Southern Medical University) Ministry of EducationGuangzhou 510515China

Extracellular vesicles(EVs)have recently emerged as a promising delivery platform for CRISPR/Cas9 ribonucleoproteins(RNPs),owing to their ability to minimize off-target effects and immune ***,enhancements are required to boost the efficiency and safety of Cas9 RNP enrichment within *** response,we employed the Fc/Spa interaction system,in which the human Fc domain was fused to the intracellular domain of PTGFRN-Δ687 and anchored to the EV ***,the B domain of the Spa protein was fused to the C domain of cargos such as Cre or *** to the robust interaction between Fc and Spa,this method enriched nearly twice the amount of cargo within the *** loaded with spCas9 RNP targeting the HSV1 genome exhibited significant inhibition of viral replication in vitro and in ***,following neuron-targeting peptide RVG modification,the in vivo dosage in neural tissues substantially increased,contributing to the clearance of the HSV1 virus in neural tissues and exhibiting a lower off-target *** findings establish a robust platform for efficient EV-based SpCas9 delivery,offering potential therapeutic advantages for HSV1 infections and other neurological disorders.

关键词： Extracellular vesicles CRISPR/Cas9 Ribonucleoproteins PTGFRN Fc/Spa HSV1 Neuron-targeting Delivery

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Farnesyltransferase inhibitor lonafarnib suppresses respiratory syncytial virus infection by blocking conformational change of fusion glycoprotein

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2970-2983页

作者： Qi Yang Bao Xue Fengjiang Liu Yongzhi Lu Jielin Tang Mengrong Yan Qiong Wu Ruyi Chen Anqi Zhou Lijie Liu Junjun Liu Changbin Qu Qingxin Wu Muqing Fu Jiayi Zhong Jianwei Dong Sijie Chen Fan Wang Yuan Zhou Jie Zheng Wei Peng Jinsai Shang Xinwen Chen Guangzhou National laboratory Guangzhou 510005China state key laboratory of Respiratory Disease Guangzhou Medical UniversityGuangzhou 511436China Wuhan Institute of Virology Chinese Academy of SciencesWuhan 430071China school of Basic Medical sciences Guangzhou Medical UniversityGuangzhou 511436China GMUGIBH Joint school of life sciences Guangzhou Medical UniversityGuangzhou 511436China Guangzhou Institutes of Biomedicine and Health Chinese Academy of SciencesGuangzhou 510530China Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201203China school of pharmaceutical Science and Technology Hangzhou lnstitute for Advanced StudyUCASHangzhou 310024China

Respiratory syncytial virus(RSV)is the major cause of bronchiolitis and pneumonia in young children and the *** are currently no approved RSV-specific therapeutic small molecules *** high-throughput antiviral screening,we identified an oral drug,the prenylation inhibitor lonafarnib,which showed potent inhibition of the RSV fusion *** exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells(HBEC).Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry,but has farnesyltransferase-independent antiviral ***-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion *** at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody ***,lonafarnib dose-dependently reduced the replication of RSV in BALB/c ***,lonafarnib could be a potential fusion inhibitor for RSV infection.

关键词： neutral metastable approved

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Identification of an immune-related gene signature for predicting prognosis and immunotherapy efficacy in liver cancer via cell-cell communication

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World Journal of Gastroenterology 2024年第11期30卷 1609-1620页

作者： Jun-Tao Li Hong-Mei Zhang Wei Wang Dong-Qing Wei College of Mathematics and Information Science Henan Normal UniversityXinxiang 453007Henan ProvinceChina College of Computer and Information Engineering Henan Normal UniversityXinxiang 453007Henan ProvinceChina state key laboratory of Microbial Metabolism and School of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghai 200240China

BACKGROUND Liver cancer is one of the deadliest malignant tumors *** has provided hope to patients with advanced liver cancer,but only a small fraction of patients benefit from this treatment due to individual *** immune-related gene signatures in liver cancer patients not only aids physicians in cancer diagnosis but also offers personalized treatment strategies,thereby improving patient survival *** several methods have been developed to predict the prognosis and immunotherapeutic efficacy in patients with liver cancer,the impact of cell-cell interactions in the tumor microenvir-onment has not been adequately *** To identify immune-related gene signals for predicting liver cancer prognosis and immunotherapy *** Cell grouping and cell-cell communication analysis were performed on single-cell RNA-sequencing data to identify highly active cell groups in immune-related *** active immune cells were identified by intersecting the highly active cell groups with B cells and T *** significantly differentially expressed genes between highly active immune cells and other cells were subsequently selected as features,and a least absolute shrinkage and selection operator(LASSO)regression model was constructed to screen for diagnostic-related *** genes that were selected more than 5 times in 10 LASSO regression experiments were included in a multivariable Cox regression ***,3 genes(stathmin 1,cofilin 1,and C-C chemokine ligand 5)significantly associated with survival were identified and used to construct an immune-related gene *** The immune-related gene signature composed of stathmin 1,cofilin 1,and C-C chemokine ligand 5 was identified through cell-cell *** effectiveness of the identified gene signature was validated based on experi-mental results of predictive immunotherapy response,tumor mutation burden analysis,immune cell infiltrat

关键词： Liver cancer Cell-cell communication Gene signature Prognosis Immunotherapy Single-cell RNA sequencing

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