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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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Polygonatum sibiricum polysaccharide extract relieves FB1-induced neurotoxicity by reducing oxidative stress and mitochondrial damage in Caenorhabditis elegans

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Food Bioscience 2022年第5期49卷 799-809页

作者： Xiaojuan Zhang Yongli Ye jiadi Sun Yida Xu Yaoguang Huang Jia-Sheng Wang Lili Tang Jian Ji Bi-yan Chen Xiulan Sun State Key Laboratory of Food Science and Technology School of Food Science and TechnologyNational Engineering Research Center for Functional FoodSynergetic Innovation Center of Food Safety and Quality ControlJiangnan UniversityWuxiJiangsu214122PR China Department of Environmental Health Science College of Public HealthUniversity of GeorgiaAthensGAUSA Zhejiang HeTianXing Biotechnology Co.Ltd. TaizhouZhejiang318000PR China

Fumonisin B1(FB1)is a mycotoxin that is harmful to the nervous system;however,there is currently a lack of studies on plant compounds that alleviate the neurotoxicity of *** sibiricum polysaccharides exhibit neuroprotective effects,but it is unclear whether they protect against FB1-induced ***,Caenorhabditis elegans(***)was used to study the alleviation effects of *** polysaccharide extract(PSPE)preprotection on FB1-induced *** pretreatment improved the behavioral deficits and neuronal damage in FB1-induced *** addition,20-200μg/mL PSPE alleviated the oxidative damage in FB1-induced *** by regulating the levels of reactive oxygen species,antioxidant enzyme activities and gene *** studies have shown that PSPE pretreatment induced mitochondrial expression,increased ATP levels and mitochondrial membrane potential,and regulated mitochondrial oxidative phosphorylation and ***,the protective effects of PSPE against FB1-induced neurotoxicity might be closely related with the reduction of oxidative stress and the regulation of mitochondria.

关键词： Polygonatum sibiricum polysaccharide Extract Fumonisin B1 Caenorhabditis elegans Neurotoxicity Oxidative stress Mitochondria

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Chemo-drugs in cell microparticles reset antitumor activity of macrophages by activating lysosomal P450 and nuclear hnRNPA2B1

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Signal Transduction and Targeted Therapy 2023年第2期8卷 757-770页

作者： Keke Wei Huafeng Zhang Shuaishuai yang Yuxiao Cui Bingxia Zhang Jincheng Liu Liang Tang Yaoyao Tan Simin Liu Shiqi Chen Wu Yuan Xiao Luo Chen Chen Fei Li Junwei Liu Jie Chen Pingwei Xu jiadi Lv Ke Tang Yi Zhang Jingwei Ma Bo Huang Department of Immunology Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430030China Department of Pathology School of Basic MedicineTongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430030China Department of Biochemistry&Molecular Biology Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430030China Cardiovascular Surgery Union HospitalHuazhong University of Science&TechnologyWuhan 430071China Department of Immunology&National Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences(CAMS)&Peking Union Medical CollegeBeijing 100005China Translational Medicine Laboratory First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325035China Biotherapy Center and Cancer Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Macrophages in tumors(tumor-associated macrophages,TAMs),a major population within most tumors,play key homeostatic functions by stimulating angiogenesis,enhancing tumor cell growth,and suppressing antitumor *** TAMs by simple,efficacious and safe approach(s)is highly desirable to enhance antitumor immunity and attenuate tumor cell ***,we used tumor cell-derived microparticles to package chemotherapeutic drugs(drug-MPs),which resulted in a significant treatment outcome in human malignant pleural effusions via neutrophil recruitments,implicating that drug-MPs might reset TAMs,considering the inhibitory effects of M2 macrophages on neutrophil recruitment and ***,we show that drug-MPs can function as an antitumor immunomodulator by resetting TAMs with M1 phenotype and IFN-β***,drug molecules in tumor MPs activate macrophage lysosomal P450 monooxygenases,resulting in superoxide anion formation,which further amplifies lysosomal ROS production and pH value by activating lysosomal ***,lysosomal Ca^(2+)signaling is activated,thus polarizing macrophages towards ***,the drug molecules are delivered from lysosomes into the nucleus where they activate DNA sensor hnRNPA2B1 for IFN-β*** lysosomal-nuclear machinery fully arouses the antitumor activity of macrophages by targeting both lysosomal pH and the nuclear innate *** findings highlight that drug-MPs can act as a new immunotherapeutic approach by revitalizing antitumor activity of *** mechanistic elucidation can be translated to treat malignant ascites by drug-MPs combined with PD-1 blockade.

关键词： drugs lysosomal immunity

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Visualization of perforin/gasdermin/complement-formed pores in real cell membranes using atomic force microscopy

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Cellular & Molecular Immunology 2019年第6期16卷 611-620页

作者： Yuying Liu Tianzhen Zhang Yabo Zhou Jiping Li Xiaoyu Liang Nannan Zhou jiadi Lv Jing Xie Feiran Cheng Yiliang Fang Yunfeng Gao Ning Wang Bo Huang Department of Immunology&National Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China Clinical Immunology Center Chinese Academy of Medical SciencesBeijing 100005China Beijing SOJO Electric Company Limited BeijingChina Department of Mechanical Science and Engineering College of EngineeringUniversity of Illinois at Urbana-ChampaignUrbanaIllinois 61801USA Laboratory for Cellular Biomechanics and Regenerative Medicine College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhanHubei 430074China Department of Biochemistry&Molecular Biology Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430030China

Different types of pores ubiquitously form in cell membranes,leading to various types of cell death that profoundly influence the fate of inflammation and the disease ***,these pores have never truly been visualized to *** force microscopy(AFM),which is emerging as a powerful tool to analyze the mechanical properties of biomolecules and cells,is actually an excellent imaging platform that allows biological samples to be visualized by probing surface roughness at the level of atomic ***,membrane pore structures were clearly visualized using *** visualization not only describes the aperture and depth of the pore complexes but also highlights differences among the pores formed by perforin and gasdermins in tumor cell membranes and by complement in immune cell ***,this type of visualization also reveals the dynamic process of pore formation,fusion,and repair.

关键词： membrane pore formation AFM perforin GSDMD/GSDME complement

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用陶瓷粉末废料生产加气混凝土砌块的研究

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新型建筑材料 2017年第9期44卷 97-99页

作者：刘家弟吴洋山东理工大学资源与环境工程学院山东淄博255000 淄博市环境保护局临淄分局山东淄博255049

研究了用陶瓷粉末废料生产加气混凝土砌块的原料及配比、发泡剂用量、水料比和养护制度等因素,确定了最佳工艺参数。研究表明,在陶瓷粉末废料用量为73.5%、生石灰用量为18%、水泥用量为7%、石膏用量为1.5%、铝粉用量为0.9 kg/(m^3制品)... 详细信息

研究了用陶瓷粉末废料生产加气混凝土砌块的原料及配比、发泡剂用量、水料比和养护制度等因素,确定了最佳工艺参数。研究表明,在陶瓷粉末废料用量为73.5%、生石灰用量为18%、水泥用量为7%、石膏用量为1.5%、铝粉用量为0.9 kg/(m^3制品)、水料比为0.6、恒温蒸气压力为1.2~1.4 MPa的蒸压养护制度下,制备的加气混凝土砌块干密度小于560 kg/m^3,抗压强度大于3.7 MPa。

关键词：墙地砖陶瓷粉末废料蒸压养护加气混凝土砌块、

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YAP Inactivation by Soft Mechanotransduction Relieves MAFG for Tumor Cell Dedifferentiation

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Research 2024年第2期6卷 401-415页

作者： jiadi Lv Xiaohan Liu Yabo Zhou Feiran Cheng Haoran Chen Shunshun Li Dianheng Wang Li Zhou Zhenfeng Wang Nannan Zhou Jie Chen Bo Huang Department of Immunology&State Key Laboratory of Common Mechanism Research for Major Diseases Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical College(PUMC)Beijing100005China Department of Histology and Embryology Basic Medical CllegeChina Medical UniversityShenyangLiaoning 11122China Department of Immunology Basic Medical Cllege China Medical UniversityShenyangLiaoning 110122China Department of Biochemistry&Molecular Biology Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430030China

Solid tumor cells live in a highly dynamic mechanical *** the extracellular-matrix-generated mechanotransduction regulates tumor cell development and differentiation remains an ***,we show that a low mechanical force generated from the soft matrix induces dedifferentiation of moderately stiff tumor cells to soft stem-cell-like ***,integrin?was identified to transduce mechano-signaling to trigger tumor cell dedifferentiation by recruiting RhoGDI1 to inactivate RhoA and subsequently Yes-associated protein(YAP).YAP inactivation relieved the inhibition of v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G(MAFG),allowing MAFG to transactivate the stemness genes NANOG,SOX2,and *** also restoredβ8 expression,thereby forming a closed mechanical ***,MAFG expression is correlated with worse *** findings provide mechanical insights into the regulation of tumor cell dedifferentiation,which has therapeutic implications for exploring innovative strategies to attack malignancies.

关键词： activation thereby MAF

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Escaping alveolar macrophage endosomal retention explains massive expansion of SARS-CoV-2 delta variant

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Signal Transduction and Targeted Therapy 2022年第1期7卷 28-30页

作者： Zhenfeng Wang Yabo Zhou Linlin Bao Dan Li jiadi Lv Dianheng Wang Shunshun Li Wei-Min Tong Jiangning Liu Chuan Qin Bo Huang Department of Immunology&National Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences(CAMS)&Peking Union Medical College100005 BeijingChina NHC Key Laboratory of Human Disease Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceCAMS and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina Department of Pathology Institute of Basic Medical SciencesCAMS and Peking Union Medical CollegeBeijingChina Department of Biochemistry&Molecular Biology Tongji Medical CollegeHuazhong University of Science&Technology430030 WuhanChina

Dear Editor,Genetic variant Delta(B.1.617.2)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which possesses a remarkable ability to transmit and spread,is currently becoming predominant *** its great harm to human beings,how the Delta variant with T478K,P681R and L452R mutations achieves its ultrafast spread remains *** of SARS-CoV-2 into host cells is mediated by a rapid enzymatic hydrolysis.

关键词： retention massive delta

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柱承重式钢结构模块建筑抗震性能试验研究

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天津大学学报（自然科学与工程技术版） 2021年第2期54卷 122-132页

作者：刘洋陈志华刘佳迪钟旭天津大学建筑工程学院天津300072 天津大学水利工程仿真与安全国家重点实验室天津300072

柱承重式钢结构模块建筑是将工厂预制完成的模块单元在现场进行拼接组装的一种新型结构体系,其建造方式及结构组成不同于传统钢结构,目前尚缺乏结构层次的抗震性能研究.本文基于角件旋转式单元间连接节点,完成了双层足尺柱承重式模块框... 详细信息

柱承重式钢结构模块建筑是将工厂预制完成的模块单元在现场进行拼接组装的一种新型结构体系,其建造方式及结构组成不同于传统钢结构,目前尚缺乏结构层次的抗震性能研究.本文基于角件旋转式单元间连接节点,完成了双层足尺柱承重式模块框架结构低周往复加载试验,得到了该结构的承载性能、破坏模式及应变分布.试验结果表明结构具有较好的滞回性能,当结构中下层模块框架在达到0.04 rad层间位移角时仍保持较高的承载能力,满足美国现行规范AISC 341-16中特殊抗弯框架的延性要求;下层框架地板梁右端最终发生贯通断裂破坏,而左端在盖板外翼缘上形成明显塑性铰;角件旋转式连接节点尽管出现一定程度的张开但可以有效地传递内力未发生破坏.当下层框架内部梁柱节点破坏后,继续进行推覆试验,单元间连接节点张开量随之增加,停止试验时承载力已超出结构发生破坏后的荷载,表明结构具有一定的残余承载性能,同时模块结构在单元内部节点发生破坏后连接区域处内力会重新分布,此时对于单元间连接节点性能应予以重视.

关键词：钢结构模块建筑柱承重式模块单元角件旋转式单元间连接节点双层足尺试验低周往复加载

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Long-term hepatitis B surface antigen kinetics after nucleos(t)ide analog discontinuation in patients with noncirrhotic chronic hepatitis B

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Liver Research 2024年第3期8卷 179-187页

作者： Lina Wu jiadi Lai Qiumin Luo Yeqiong Zhang Chaoshuang Lin Dongying Xie Youming Chen Hong Deng Zhiliang Gao Liang Peng Wenxiong Xu Department of Infectious Diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Guangdong Key Laboratory of Liver Disease Research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Key Laboratory of Tropical Disease Control Ministry of EducationSun Yat-sen UniversityGuangzhouGuangdongChina

Background and aim Few studies have reported hepatitis B surface antigen(HBsAg)kinetics after nucleos(t)ide analog(NA)discontinuation in patients with noncirrhotic chronic hepatitis B(CHB).The study specifically investigated long-term HBsAg kinetics after NA *** Between January 2014 to January 2024,this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation ***,clinical,and laboratory data were collected and analyzed after NA *** Ninety-six patients who finished 5 years of follow-up were *** remained undetectable in 29 patients with end of treatment(EOT)HBsAg *** 67 patients with EOT HBsAg positivity,HBsAg seroclearance occurred in 12(17.9%)patients with an estimated annual incidence of HBsAg seroclearance of 3.6%.Patients with EOT HBsAg levels of≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of>1000 IU/mL(33.3%vs.5.4%).The proportion of patients with HBsAg≤1000 IU/mL increased during *** regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/*** optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/*** Patients with EOT HBsAg negativity experienced no relapse and maintained HBsAg seroclearance during 5 years of follow-up after NA discontinuation.A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of≤1000 IU/mL during 5 years of follow-up after NA *** monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation.

关键词： Hepatitis B virus(HBV) Chronic hepatitis B(CHB) Hepatitis B surface antigen(HBsAg) Nucleos(t)ide analogs(NAs) Quantitative HBsAg Kinetics

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STAT3/p53 pathway activation disrupts IFN-β-induced dormancy in tumor-repopulating cells

STAT3/p53 pathway activation disrupts IFN-β-induced dormanc...

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第十三届全国免疫学学术大会

作者： jiadi Lv Jinyan Liu Bo Huang Department of Immunology Institute of Basic Medical Sciences Clinical Immunology Center Chinese Academy of Medical Sciences

Dynamic interaction with the immune system profoundly regulates tumor cell ***, it is unclear how immunological cues trigger cancer cell-intrinsic signaling pathways for entering into ***, we show that IFN-β treatment induced tumor-repopulating cells(TRC) to enter dormancy through an indolamine 2,3-dioxygenase/kynurenine/aryl hydrocarbon receptor/p27-dependent(IDO/Kyn/AhR/p27-dependent) *** to block this metabolic circuitry did not relieve dormancy, but led to apoptosis of dormant TRCs in murine and human melanoma ***, blocking AhR redirected IFN-β signaling to STAT3 phosphorylation through both tyrosine and serine sites, which subsequently facilitated STAT3 nuclear translocation and subsequent binding to the p53 promoter in the *** of p53 in turn disrupted the pentose phosphate pathway, leading to excessive ROS production and dormant TRC ***, in melanoma patients, high expression of IFN-β correlated with tumor cell *** of this mechanism for controlling TRC dormancy by IFN-β provides deeper insights into cancer-immune interaction and potential new cancer immunotherapeutic modalities.

关键词： Cancer Immunology Melanoma Signal transduction Stem cells

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