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Carrimycin ameliorates lipopolysaccharide and cecal ligation and puncture-induced sepsis in mice

Chinese Journal of Natural Medicines 2024年第3期22卷 235-248页

作者： LAI Junzhong LIANG Jiadi CHEN Kunsen GUAN Biyun CHEN Zhirong CHEN Linqin FAN Jiqiang ZHANG Yong LI Qiumei SU Jingqian CHEN Qi LIN Jizhen The Cancer center Fujian Medical University Union HospitalFuzhou 350001China fujian key laboratory of innate immune biology Biomedical Research Center of South ChinaFujian Normal UniversityFuzhou 350117China The Department of Otolaryngology Head&Neck SurgeryUniversity of Minnesota Medical SchoolMinneapolisMN 55455USA

Carrimycin(CA),sanctioned by china’s National Medical Products Administration(NMPA)in 2019 for treating acute bronchitis and sinusitis,has recently been observed to exhibit multifaceted biological activities,encompassing anti-inflammatory,antiviral,and anti-tumor *** these applications,its efficacy in sepsis treatment remains *** study introduces a novel function of CA,demonstrating its capacity to mitigate sepsis induced by lipopolysaccharide(LPS)and cecal ligation and puncture(CLP)in mice *** research employed in vitro assays,real-time quantitative polymerase chain reaction(RT-qPCR),and RNA-seq analysis to establish that CA significantly reduces the levels of pro-inflammatory cytokines,namely tumor necrosis factor-alpha(TNF-α),interleukin 1 beta(IL-1β),and interleukin 6(IL-6),in response to LPS ***,Western blotting and immunofluorescence assays revealed that CA impedes Nuclear Factor Kappa B(NF-κB)activation in LPS-stimulated RAW264.7 *** these findings,in vivo experiments demonstrated that CA effectively alleviates LPS-and CLP-triggered organ inflammation in C57BL/6 *** insights were gained through 16S sequencing,highlighting CA’s pivotal role in enhancing gut microbiota diversity and modulating metabolic pathways,particularly by augmenting the production of short-chain fatty acids in mice subjected to ***,a comparative analysis revealed that CA’s anti-inflammatory efficacy surpasses that of equivalent doses of aspirin(ASP)and ***,these findings suggest that CA exhibits significant therapeutic potential in sepsis *** discovery provides a foundational theoretical basis for the clinical application of CA in sepsis management.

关键词： Carrimycin Inflammation Lipopolysaccharide Cecal ligation and puncture Sepsis Gut microbiota

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Aloin ameliorates cecal ligation and puncture-induced sepsis in mice by attenuating inflammation and modulating gut microbiota

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Food science and Human Wellness 2024年

作者： Jingqian Su Jianbin Xiao Siyuan Chen Heng Zhao Xiaoni Zhang Zhihua Feng Kunsen Chen Biyun Guan Wenzhi Chen Youqiang Chen Duo Chen Qi Chen fujian key laboratory of innate immune biology， biomedical research center of south china， college of life science， fujian normal university The Public Service Platform for Industrialization Development Technology of Marine Biological Medicine and Products of the State Oceanic Administration， fujian key laboratory of Special Marine Bioresource Sustainable Utilization， southern Institute of Oceanography， college of life science， fujian normal university

Most Aloe species are used as new food or functional food ingredient. Even though widely known for its health benefits， the anti-inflammatory effects and underlying mechanisms of Aloin (Alo)， an anthraquinone compound isolated from plant species of the genus Aloe， remain unidentified. Here， we investigated the protective effects of Alo against cecal ligation and puncture (CLP)-induced sepsis and microflora in mice. Alo significantly improved CLP-induced sepsis and the survival rate of septic mice， downregulated the expression of proinflammatory factors， and decreased the infiltration of inflammatory cells in tissues. Alo upregulated the proportion of peritoneal macrophages， reduced the number of peritoneal bacteria， decreased the content of short-chain fatty acids and bile acids in the abdominal cavity， and suppressed TLR-2/4/NF-κB/NLRP3/Caspase-1/3/8 signaling. Furthermore， Alo altered the composition of the microbiome and promoted the growth of Lactobacillus， which showed a stronger anti-inflammatory effect. Whole-genome analysis identified the genes Saa3， Il10， Fpr1， and Eif4a1 associated with the protective effects of Alo in mice with CLP-induced sepsis. Overall， our results provide novel insights into the therapeutic potential and mechanism of action of Alo in the treatment of sepsis.

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Carrimycin ameliorates lipopolysaccharide and cecal ligation and puncture-induced sepsis in mice

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Chinese Journal of Natural Medicines 2024年第03期 235-248页

作者： LAI Junzhong LIANG Jiadi CHEN Kunsen GUAN Biyun CHEN Zhirong CHEN Linqin FAN Jiqiang ZHANG Yong LI Qiumei SU Jingqian CHEN Qi LIN Jizhen The Cancer center Fujian Medical University Union Hospital fujian key laboratory of innate immune biology Biomedical Research Center of South China Fujian Normal University The Department of Otolaryngology Head & Neck Surgery University of Minnesota Medical School

Carrimycin(CA), sanctioned by china's National Medical Products Administration(NMPA) in 2019 for treating acute bronchitis and sinusitis, has recently been observed to exhibit multifaceted biological activities, encompassing anti-inflammatory, antiviral, and anti-tumor properties. Despite these applications, its efficacy in sepsis treatment remains unexplored. This study introduces a novel function of CA, demonstrating its capacity to mitigate sepsis induced by lipopolysaccharide(LPS) and cecal ligation and puncture(CLP) in mice models. Our research employed in vitro assays, real-time quantitative polymerase chain reaction(RT-qPCR), and RNA-seq analysis to establish that CA significantly reduces the levels of pro-inflammatory cytokines, namely tumor necrosis factor-alpha(TNF-α), interleukin 1 beta(IL-1β), and interleukin 6(IL-6), in response to LPS stimulation. Additionally, Western blotting and immunofluorescence assays revealed that CA impedes Nuclear Factor Kappa B(NF-κB) activation in LPS-stimulated RAW264.7cells. Complementing these findings, in vivo experiments demonstrated that CA effectively alleviates LPS-and CLP-triggered organ inflammation in C57BL/6 mice. Further insights were gained through 16S sequencing, highlighting CA's pivotal role in enhancing gut microbiota diversity and modulating metabolic pathways, particularly by augmenting the production of short-chain fatty acids in mice subjected to CLP. Notably, a comparative analysis revealed that CA's anti-inflammatory efficacy surpasses that of equivalent doses of aspirin(ASP) and TIENAM. Collectively, these findings suggest that CA exhibits significant therapeutic potential in sepsis *** discovery provides a foundational theoretical basis for the clinical application of CA in sepsis management.

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Synergistic glycolysis disturbance for cancer therapy by a MOF-based nanospoiler

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Biophysics Reports 2023年第3期9卷 134-145页

作者： Xuemei Zeng Yihang Ruan Lun Wang Jinpeng Deng Shuangqian Yan key laboratory of innate immune biology of fujian Province Biomedical Research Center of South China College of Life Sciences Fujian Normal University The Straits Institute of Flexible Electronics (SIFE Future Technologies) the Straits Laboratory of Flexible Electronics (SLoFE) Fujian Normal University

Increased glycolysis for promoting adenosine triphosphate(ATP) generation is one of the hallmarks of cancer. Although reducing glucose intake or depriving cellular glucose can delay the growth of tumors to some extent, their therapeutic efficacy is a highly needed improvement for clinical translation. Herein, we found that mannose synergistic with glucose oxidase(GOx) can induce cell death by ATP inhibition, autophagy activation, and apoptosis protein upgradation. By using biodegradable zeolitic imidazolate frameworks(ZIF-8) as a nanocarrier(denoted as ZIF-8/M&G), the mannose and GOx can accumulate at the tumor site while having no obvious long-term toxicity. At the tumor site, GOx inhibits glycolysis by converting glucose and oxygen to H2O2and gluconic acid, realizing oxidation therapy and expediting the degradation of the p H-responsive ZIF-8 nanoparticles, respectively. Simultaneously, mannose disturbs sugar metabolism and reduces oxygen consumption, which in turn promotes the GOx oxidation process. The concerted glycolysis inhibition through interactions between mannose and GOx endows ZIF-8/M&G nanospolier with excellent therapeutic efficacy both in vitro and in vivo. Synergistic glycolysis disturbance by the designed nanospoiler in this work proposes a versatile approach for metabolism disturbance to tumor treatment.

关键词： Glycolysis disturbance Energy deprivation Drug delivery Zeolitic imidazolate frameworks Metal-organic frameworks

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Ubiquitin:there’s no quitting

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science Bulletin 2020年第16期65卷 1327-1329,M0003页

作者： Abdullah F.U.H.Saeed Songying Ouyang The key laboratory of innate immune biology of fujian Province Provincial University Key Laboratory of Cellular Stress Response and Metabolic RegulationBiomedical Research Center of South ChinaKey Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of EducationCollege of Life SciencesFujian Normal UniversityFuzhou 350117China laboratory for Marine biology and Biotechnology Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266237China college of Chemistry and Materials science Fujian Normal UniversityFuzhou 350117China

innate immunity is the first line of defense against pathogens in the host cells,which include neutrophils,monocytes,macrophages,eosinophils,mast cells,dendritic cells,and so ***,in what way these cells have changed the innate immune responses stays *** immune system is complex and protects from countless *** uses pattern-recognition receptors(PRRs)to recognize evolutionary conserved pathogen-associated molecular patterns(PAMPs)from pathogens[1].

关键词：免疫反应 immunity pattern

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research progress in electrospinning engineering for all-solid-state electrolytes of lithium metal batteries

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Journal of Energy Chemistry 2021年第10期30卷 253-268,I0008页

作者： Manxi Wang Yaling Wu Min Qiu Xuan Li Chuanping Li Ruiling Li Jiabo He Ganggang Lin Qingrong Qian Zhenhai Wen Xiaoyan Li Ziqiang Wang Qi Chen Qinghua Chen Jinhyuk Lee Yiu-Wing Mai Yuming Chen college of Environmental science and Engineering Fujian Normal UniversityFuzhou 350000FujianChina fujian key laboratory of innate immune biology Biomedical Research Center of South Chinaand College of Life ScienceFujian Normal UniversityFuzhou 350000FujianChina college of Chemistry and Materials science Fujian Normal UniversityFuzhou 350000FujianChina State Grid fujian Maintenance Company Fuzhou 350000FujianChina CAS key laboratory of Design and Assembly of Functional Nanostructures and Fujian Provincial Key Laboratory of NanomaterialsFujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhou 350000FujianChina Department of Nuclear science and Engineering and Department of Materials science and Engineering Massachusetts Institute of TechnologyCambridgeMA 02139United States Department of Mining and Materials Engineering McGill UniversityMontréalQC H3A 0C5Canada Centre for Advanced Materials Technology(CAMT) School of AerospaceMechanical and Mechatronics Engineering J07The University of SydneyNSW 2006Australia State key laboratory of Structural Chemistry Fuzhou 350000FujianChina

Owing to safety issue and low energy density of liquid lithium-ion batteries(LIBs),all-solid-state lithium metal batteries(ASLMBs)with unique all-solid-state electrolytes(SEs)have attracted wide *** arises mainly from the advantages of the SEs in the suppression of lithium dendrite growth,long cycle life,and broad working temperature range,showing huge potential applications in electronic devices,electric vehicles,smart grids,and biomedical ***,SEs suffer from low lithiumion conductivity and low mechanical integrity,slowing down the development of practical *** engineering is of great efficiency in tuning the structure and composition of the SEs with improved lithium-ion conductivity and mechanical *** various available technologies for nanostructure engineering,electrospinning is a promising technique because of its simple operation,cost-effectiveness,and efficient integration with different *** this review,we will first give a simple description of the electrospinning ***,the use of electrospinning technique in the synthesis of various SEs is summarized,for example,organic nanofibrous matrix,organic/inorganic nanofibrous matrix,and inorganic nanofibrous matrix combined with other *** current development of the advanced architectures of SEs through electrospinning technology is also presented to provide references and ideas for designing high-performance ***,an outlook and further challenges in the preparation of advanced SEs for ASLMBs through electrospinning engineering are given.

关键词： Solid-state composite electrolyte Lithium metal batteries Electrospinning engineering Organic/inorganic matrices

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TREX1 gene deletion accelerates cell senescence with abnormal activation of the cGAS-STING pathway

TREX1 gene deletion accelerates cell senescence with abnorma...

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第十四届全国免疫学学术大会

作者： Hekang Du Nanyang Xiao Sitong Zhang Lili Lin Miaohui Huang Qi Chen The key laboratory of innate immune biology of fujian Province biomedical research center of south china college of life sciences Fujian Normal University

Introduction:Cell senescence is traditionally described as an irreversible stagnation of the cell cycle,in which cells lose their proliferation *** cells have several major *** most notable characteristic is the secretion of various pro-inflammatory proteins,such as inflammatory cytokines,chemokines,cell growth,and *** cytokines secreted by senescent cells are collectively referred to as senescence-related secretory phenotype(SASP).Trex1 expresses DNase Ⅲ protein,the C-terminus is located in the endoplasmic reticulum,and the N-terminus has DNase exonuclease *** deletion and point mutation can cause a variety of autoimmune diseases..Interestingly,the cytokines induced by abnormal Trex1 are mostly the same as SASP ***,it is unclear if the abnormality of trex1 gene is related to cellular *** importantly,whether there is abnormal cellular senescence in autoimmune patients is worth of our ***:Cell passaging experiments and cell senescence signs detection results demonstrate that,compared with wildtype,the homozygous deletion of Trex1 mouse embryonic fibroblsts(MEFs) enter the state of cell senescence faster,and SASP cytokines are detected ***1 will cause DNA damage and ROS generation to continuously activate the DNA damage response(DDR),Interestingly,Etoposides(an inhibitor of topoisomerase-Ⅱ) and Ionizing radiation(IR) can exacerbate this process.A TBK1 inhibitor,BX795,can ameliorate the course of cell senescence in Trex1 *** the same time,in vivo data verified the abnormal cell senescence in Trex1 ***:Our data demonstrate that the Trex1 gene deletion can accelerate cell senescence by abnormally activating the cGAS-STING pathway and provide new insight into the development and treatment of autoimmune diseases.

关键词： Trex1 Senescence cGAS-STING Autoimmune diseases

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Structural basis of AimP signaling molecule recognition by AimR in Spbeta group of bacteriophages

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Protein & Cell 2019年第2期10卷 131-136页

作者： Xiangkai Zhen Huan Zhou Wei Ding Biao Zhou Xiaolong Xu Vanja Perculija Chun-Jung Chen Ming-Xian Chang Muhammad Iqbal Choudhary Songying Ouyang The key laboratory of innate immune biology of fujian Provinee Biomedical Research Center of South ChinaCollege of Life SciencesFujian Normal UniversityFuzhou 350117China Provincial university key laboratory of Cellular Stress Response and Metabolic Regulation College of Life SciencesFujian Normal UniversityFuzhou 350117China Shanghai Institute of Applied Physics Chinese Academy of SciencesShanghai 201204China CAS key laboratory of Soft Matter Physics Institute of PhysicsChinese Academy of SciencesBeijing 100190China National laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China In stitute of Biotech no logy National Cheng Kung UniversityTainan 701China State key laboratory of Freshwater Ecology and Biotech no logy Institute of HydrobiologyChinese Academy of SciencesWuhan 430072China H.E.J.research Institute of Chemistry International Center for Chemical and Biological SciencesUniversity of KarachiKarachi 75270Pakistan

Dear Editor,Quorum sensing(QS)is a widespread phenomenon in bacteria which enables them to participate in cell-to-cell communication by producing and responding to small signal molecules,thus synchronously altering their behavior depending on population density(Singh et al.,2000;Miller and Bassler,2001).Through QS,bacteria coordinate processes such as expression of virulenee factors(Slamti and Lereclus,2002),biofilm formation(Parashar et al.,2011),sporulation(Perego et al.,1996),conjugation(Kozlowicz et al.,2006),antibiotic synthesis(Miller and Bassler,2001;Whiteley et al.,2017)etc.

关键词： Editor QS cell

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Legionella pneumophila temporally regulates the activity of ADP/ATP translocases by reversible ADP-ribosylation

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mlife 2022年第1期1卷 51-65页

作者： Jiaqi Fu Pengwei Li Hongxin Guan Dan Huang Lei Song Songying Ouyang Zhao-Qing Luo Department of Biological sciences Purdue Institute for InflammationImmunology and Infectious DiseasePurdue UniversityWest LafayetteIndianaUSA Provincial university key laboratory of Cellular Stress Response and Metabolic Regulation The Key Laboratory of Innate Immune Biology of Fujian ProvinceBiomedical Research Center of South ChinaKey Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of EducationCollege of Life SciencesFujian Normal UniversityFuzhouChina key laboratory of Organ Regeneration and Transplantation of the Ministry of Education State Key Laboratory of Zoonotic DiseasesDepartment of Respiratory MedicineCenter for Pathogen Biology and Infectious DiseasesThe First Hospital of Jilin UniversityChangchunChina

The mitochondrion is an important signaling hub that governs diverse cellular functions,including metabolism,energy production,and *** the hundreds of effectors translocated into host cells by the Dot/Icm system of Legionella pneumophila,several are targeted to mitochondria but the function of most of them remains *** recent study found that the effector Ceg3 inhibits the activity of ADP/ATP translocases(ANTs)by ADP-ribosylation(ADPR).Here,we show that the effect of Ceg3 is antagonized by Larg1,an effector encoded by lpg0081,a gene that is situated next to ***1 functions to reverse Ceg3-mediated ADPR of ANTs by cleaving the N-glycosidic bond between the ADPR moiety and the modified arginine residues in ANTs,leading to restoration of their activity in ADP/ATP *** analysis of Larg1 and its complex with ADPR reveals that this ADPR glycohydrolase harbors a unique macrodomain that catalyzes the removal of ADPR modification on *** results also demonstrate that together with Ceg3,Larg1 imposes temporal regulation of the activity of ANTs by reversible ADPR during *** infection.

关键词： energy metabolism metaeffector mitochondria type IV secretion

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CASTING: A Potent Supramolecular Strategy to Cytosolically Deliver STING Agonist for Cancer Immunotherapy and SARS-CoV-2 Vaccination

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CCS Chemistry 2023年第4期5卷 885-901页

作者： Jun-Jun Wu Fang-Yuan Chen Bei-Bei Han Hong-Qing Zhang Lang Zhao Zhe-Rui Zhang Juan-Juan Li Bo-Dou Zhang Ya-Nan Zhang Yu-Xin Yue Hong-Guo Hu Wen-Hao Li Bo Zhang Yong-Xiang Chen Dong-Sheng Guo Yan-Mei Li key Lab of Bioorganic Phosphorus Chemistry and Chemical biology(Ministry of Education) Department of ChemistryCenter for Synthetic and Systems BiologyTsinghua UniversityBeijing 100084 college of Chemistry Key Laboratory of Functional Polymer MaterialsMinistry of EducationState Key Laboratory of Elemento-Organic ChemistryNankai UniversityTianjin 300071 key laboratory of Special Pathogens and Biosafety Center for Emerging Infectious DiseasesWuhan Institute of VirologyChinese Academy of SciencesWuhan 430071 university of Chinese Academy of sciences Beijing 100049 Beijing Institute for Brain Disorders Beijing 100069 key laboratory of innate immune biology of fujian Province Provincial University Key Laboratory of Cellular Stress Response and Metabolic RegulationBiomedical Research Center of South ChinaCollege of Life SciencesFujian Normal UniversityFuzhou 350117

Stimulator of interferon genes,namely STING,an adaptor protein located in the endoplasmic reticulum,has been recognized as a shining target for cancer and infection ***,STING agonists cyclic dinucleotides(CDNs)have shown almost zero efficacy in phase I clinical trials as a monotherapy,likely due to poor cellular permeability and rapid diffusion despite intratumoral *** deficiencies further affect other applications of CDNs,such as pandemic SARS-CoV-2 prevention and ***,we rationally design a supramolecular cytosolic delivery system based on controllable recognition of calixarene,namely CASTING(CAlixarene-STING),to improve CDN druggability,including degradation stability,cellular permeability,and tissue *** efficiently enhances the immunostimulatory potency of CDGSF[a chemically modified cyclic di-GMP(CDG)]to generate an immunogenic microenvironment for melanoma regression,anti-PD-1 response rate increase,and durable memory formation against tumor *** importantly,CASTING displays a superior adjuvant activity on SARSCoV-2 recombinant spike/receptor binding domain vaccines,inducing robust and coordinated T-cell and antibody responses against SARS-CoV-2 infection in ***,the CASTING design represents an innovative advancement to facilitate the clinical translational capability of STING agonists.

关键词： STING agonist cyclic dinucleotides calixarene supramolecular delivery cancer immunotherapy SARS-CoV-2 vaccine adjuvant

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