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Targeted screening of an anti-inflammatory polypeptide from Rhopilema esculentum Kishinouye cnidoblasts and elucidation of its mechanism in alleviating ulcerative colitis based on an analysis of the gut microbiota and metabolites

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Food Science and Human Wellness 2024年第3期13卷 1336-1347页

作者： Ziyan Wang Qiuyue Shi Ying Feng jiaojiao Han Chenyang lu Jun Zhou Zhonghua Wang Xiurong Su State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products Ningbo UniversityNingbo 315000China School of Marine Science Ningbo UniversityNingbo 315000China Key Laboratory of Aquaculture Biotechnology(Ningbo University) Ministry of EducationNingbo UniversityNingbo 315000China College of Life Sciences Tonghua Normal UniversityTonghua 134000China Shandong Beiyou Biotechnology Co. Ltd.Weifang 261000China

Ulcerative colitis(UC)is a recurrent inflammatory bowel disease that imposes a severe burden on families and society.In recent years,exploiting the potential of marine bioactive peptides for the treatment of diseases has become a topic of intense research interest.This study revealed the mechanism underlying the protective effect of the dominant polypeptide PKKVV(Pro-Lys-Lys-Val-Val)of Rhopilema esculentum cnidoblasts against DSS-induced UC through a combined analysis of the metagenome and serum metabolome.Specifically,the polypeptide composition of R.esculentum cnidoblasts was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF/TOF-MS).Molecular docking showed that the dominant peptide PKKVV could bind better with tumor necrosis factor-α(TNF-α)than the original ligand.Subsequent animal experiments suggested that PKKVV could modulate disorganized gut microorganisms in mice with UC;affect serum metabolites through the arachidonic acid,glycerophospholipid and linoleic acid metabolism pathways;and further alleviate UC symptoms.This study provides a reference for the comprehensive development of marine bioactive substances and nonpharmaceutical treatments for UC.

关键词： Ulcerative colitis Rhopilema esculentum Kishinouye Cnidoblasts Marine bioactive polypeptides Metagenome Serum metabolome

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AI for science: Predicting infectious diseases

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Journal of Safety Science and Resilience 2024年第2期5卷 130-146页

作者： Alexis Pengfei Zhao Shuangqi Li Zhidong Cao Paul Jen-Hwa Hu jiaojiao Wang Yue Xiang Da Xie Xi lu Institute of Automation Chinese Academy of SciencesUniversity of Chinese Academy of SciencesBejing 100090China Systems Engineering Cornll UniversityIthacaNY 14853USA David Eccles School of Business the University of UtahUtahUSA Collge of Electrical Engineering Sichuan UniversityChina Department of Electrical Engineering Shanghai Jiao Tong UniversityShanghai 200240China School of Electrical Engineering Southeast UniversityNanjing 210096China

The global health landscape has been persistently challenged by the emergence and re-emergence of infectious diseases.Traditional epidemiological models,rooted in the early 2oth century,have provided foundational in-sights into disease dynamics.However,the intricate web of modern global interactions and the exponential growth of available data demand more advanced predictive tools.This is where AI for Science(AI4S)comes into play,offering a transformative approach by integrating artificial intelligence(Al)into infectious disease pre-diction.This paper elucidates the pivotal role of AI4s in enhancing and,in some instances,superseding tradi-tional epidemiological methodologies.By harnessing AI's capabilities,AI4S facilitates real-time monitoring,sophisticated data integration,and predictive modeling with enhanced precision.The comparative analysis highlights the stark contrast between conventional models and the innovative strategies enabled by AI4S.In essence,Al4S represents a paradigm shift in infectious disease research.It addresses the limitations of traditional models and paves the way for a more proactive and informed response to future outbreaks.As we navigate the complexities of global health challenges,Al4S stands as a beacon,signifying the next phase of evolution in disease prediction,characterized by increased accuracy,adaptability,and efficiency.

关键词： AI for science(AI4S) Data integration Global healthchallenges Infectious disease prediction Predictive modeling Real-timemonitoring

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Analysis and Characterization of the GABA Transaminase and Succinate Semialdehyde Dehydrogenase Genes in the Microalga Isochrysis zhanjiangensis in Response to Abiotic Stresses

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Journal of Ocean University of China 2024年第3期23卷 775-785页

作者： TIAN jiaojiao ZHANG Lin lu Xinyue YE Lingzhi WU Yuanyuan CHEN Deshui CAO Jiayi JIANG Jiaxin XU Jilin YAN Xiaojun Key Laboratory of Marine Biotechnology of Zhejiang Province School of Marine SciencesNingbo UniversityNingbo 315211China Key Laboratory of Aquacultural Biotechnology Ministry of Education Ningbo UniversityNingbo 315211China Laizhou Bay Marine Technology Co. Ltd.Yantai 261400China Fujian Dalai Seed Science and Technology Co. Ltd.Ningde 352101China

Gamma-aminobutyric acid(GABA),widely existing in different organisms,is rapidly accumulated in plants in response to environmental stresses.The main biosynthesis and degradation pathways of GABA constitute the GABA shunt,which is tied to the tricarboxylic acid(TCA)cycle.GABA transaminase(GABA-T)and succinate semialdehyde dehydrogenase(SSADH)are two essential enzymes for the GABA degradation pathway.While there are abundant studies on GABA shunt in higher plants at the physiological and genetic levels,research on its role in microalgae remains limited.This study aimed at exploring the function of GABA-T and SSADH genes in Isochrysis zhanjiangensis,an important diet microalga,under different stresses.We cloned two GABA-T genes,IzGABA-T1 and IzGABA-T2,and one SSADH gene IzSSADH from Isochrysis zhanjiangensis and conducted heterologous expression experiments.The results showed that the overexpression of IzGABA-T1 or IzGABA-T2 enhanced the survival rates of yeast transformants under heat or NaCl stress,while the overexpression of IzSSADH improved yeast tolerance to NaCl stress but had no obvious effect on heat stress.Additionally,the results of quantitative real-time polymerase chain reaction(qPCR)showed that IzGABA-T1 transcription increased in the HT(salinity 25,35℃)and LS(salinity 15,25℃)groups.At 24 h,the IzGABA-T2 transcriptions increased in the HT,LS,and HS(salinity 35,25℃)groups,but their transcription levels decreased in all groups at 48 h.IzSSADH transcription increased in the LS group.These results suggest that IzGABA-T1,IzGABA-T2,and IzSSADH are associated with temperature and salinity stresses and possess a certain preference for different stresses.

关键词： abiotic stress GABA heterologous expression Isochrysis zhanjiangensis transcription

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Protective effects and microarray-based mechanism of sea cucumber hydrolysates against high-glucose induced nephrotoxicity in mouse glomerulus mesangial cells

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未来食品学报(英文) 2024年第3期4卷 233-240页

作者： Lingxin Geng jiaojiao Han Jun Zhou Ye Li Tinghong Ming Zhen Zhang Chenyang lu Xiurong Su State Key Laboratory for Quality and Safety of Argo-products School of Marine ScienceNingbo UniversityNingbo 315211China

Diabetic nephropathy(DN)is a common type of end-stage renal disease and glomerular mesangial cells(GMCs)are widely used as a cell model for DN.This study firstly investigated the inhibitory effects of the Apostichopus japonicus and Acaudina leucoprocta hydrolysates on cellular growth under high-glucose treatment,better inhibitory effect of A.japonicus hydrolysate was observed compared to that of A.leucoprocta hydrolysate.Subsequently,the global transcription profiles obtained via microarray analysis showed that 6070 and 7015 genes were identified in the A.japonicus and A.leucoprocta groups compared with the model group,respectively.Among them,transcriptions of the slc30a4,slc35dl,tppp3,tp53inpl,bcl-2,apafl,alox12b and adrala genes were restored from the levels of the model group to those of the control group,contributed to cell mitosis and proliferation in both treatment groups.In addition,other apoptosis-related genes,such as bcl-6,clu,foxo3 and akt,showed opposite trends between two groups,which might cause the difference in inhibitory effect.We preliminarily proposed that the regulation effects of A.japonicus and A.leucoprocta on the genes involved in cellular mitosis,proliferation and apoptosis,might contribute to their inhibitory activity on GMCs under high-glucose environment.

关键词： Diabetic nephropathy Apostichopus japonicus Acaudina leucoprocta Hydrolysate Rat mesangial cell Microarray

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Strip segmentation of oceanic internal waves in SAR images based on TransUNet

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Acta Oceanologica Sinica 2023年第10期42卷 67-74页

作者： Kaituo Qi Hongsheng Zhang jiaojiao lu Yinggang Zheng Zhouhao Zhang College of Ocean Science and Engineering Shanghai Maritime UniversityShanghai 201306China Translational Research Institute of Brain and Brain-Like Intelligence Shanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghai 200434China

The development of oceanic remote sensing artificial intelligence has made possible to obtain valuable information from amounts of massive data.Oceanic internal waves play a crucial role in oceanic activity.To obtain oceanic internal wave stripes from synthetic aperture radar(SAR)images,a stripe segmentation algorithm is proposed based on the TransUNet framework,which is a combination of U-Net and Transformer,which is also optimized.Through adjusting the number of Transformer layer,multi-layer perceptron(MLP)channel,and Dropout parameters,the influence of over-fitting on accuracy is significantly weakened,which is more conducive to segmenting lightweight oceanic internal waves.The results show that the optimized algorithm can accurately segment oceanic internal wave stripes.Moreover,the optimized algorithm can be trained on a microcomputer,thus reducing the research threshold.The proposed algorithm can also change the complexity of the model to adapt it to different date scales.Therefore,TransUNet has immense potential for segmenting oceanic internal waves.

关键词： oceanic internal waves deep learning stripe segmentation synthetic aperture radar TransUNet

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FGF4 protects the liver from immune-mediated injury by activating CaMKKβ-PINK1 signal pathway to inhibit hepatocellular apoptosis

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1605-1623页

作者： Zhifeng Huang Tongtong Pan Liang Xu lu Shi Xiong Ma Liya Zhou luyao Wang jiaojiao Wang Guoqing Zhu Dazhi Chen Lingtao Song Xiaomin Pan Xiaodong Wang Xiaokun Li Yongde luo Yongping Chen Hepatology Diagnosis and Treatment Center Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseasesthe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325035China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)&School of Pharmaceutical SciencesWenzhou Medical UniversityWenzhou 325035China School of Laboratory Medicine and Life Sciences Wenzhou Medical University&Key Laboratory of Laboratory MedicineMinistry of EducationWenzhou Medical UniversityWenzhou 325035China Division of Gastroenterology and Hepatology Key Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200001China Hangzhou Medical College Hangzhou 311300China

Immune-mediated liver injury (ILI) is a condition where an aberrant immune response due to various triggers causes the destruction of hepatocytes. Fibroblast growth factor 4 (FGF4) was recently identified as a hepatoprotective cytokine;however, its role in ILI remains unclear. In patients with autoimmune hepatitis (type of ILI) and mouse models of concanavalin A (ConA)- or S-100-induced ILI, we observed a biphasic pattern in hepatic FGF4 expression, characterized by an initial increase followed by a return to basal levels. Hepatic FGF4 deficiency activated the mitochondria-associated intrinsic apoptotic pathway, aggravating hepatocellular apoptosis. This led to intrahepatic immune hyper-reactivity, inflammation accentuation, and subsequent liver injury in both ILI models. Conversely, administration of recombinant FGF4 reduced hepatocellular apoptosis and rectified immune imbalance, thereby mitigating liver damage. The beneficial effects of FGF4 were mediated by hepatocellular FGF receptor 4, which activated the Ca^(2+)/calmodulin-dependent protein kinasekinase 2 (CaMKKβ) and its downstream phosphatase and tensin homologue-induced putative kinase 1 (PINK1)-dependent B-cell lymphoma 2-like protein 1-isoform L (Bcl-XL) signalling axis in the mitochondria. Hence, FGF4 serves as an early response factor and plays a protective role against ILI, suggesting a therapeutic potential of FGF4 and its analogue for treating clinical immune disorder-related liver injuries.

关键词： Fibroblast growthfactor 4 Fibroblast growth factor receptor 4 Immune liver injury Ca^(2+)/Calmodulin dependent protein

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Anti-atherosclerotic effects and molecular targets of ginkgolide B from Ginkgo biloba

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Acta Pharmaceutica Sinica B 2024年第1期14卷 1-19页

作者： Weile Ye jiaojiao Wang Peter JLittle Jiami Zou Zhihua Zheng Jing lu Yanjun Yin Hao Liu Dongmei Zhang Peiqing Liu Suowen Xu Wencai Ye Zhiping Liu International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of China Jinan UniversityGuangzhou 510632China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research College of PharmacyJinan UniversityGuangzhou 510632China State Key Laboratory of Bioactive Molecules and Druggability Assessment Jinan UniversityGuangzhou 510632China Pharmacy Australia Centre of Excellence School of PharmacyUniversity of QueenslandWoolloongabba QLD 4102Australia Sunshine Coast Health Institute and School of Health and Behavioural Sciences University of the Sunshine CoastBirtinya QLD 4575Australia National-Local Joint Engineering Lab of Druggability and New Drugs Evaluation Guangdong Provincial Key Laboratory of New Drug Design and EvaluationSun Yat-sen UniversityGuangzhou 510006China School of Pharmacy Bengbu Medical CollegeBengbu 233030China Institute of Endocrine and Metabolic Diseases the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China

Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases(CVDs),the world’s primary cause of death.Ginkgo biloba,a well-known traditional Chinese medicine with notable cardiovascular actions,has been used as a cardio-and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries.Preclinical studies have shown that ginkgolide B,a bioactive component in Ginkgo biloba,can ameliorate atherosclerosis in cultured vascular cells and disease models.Of clinical relevance,several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases,such as ischemia stroke.Here,we present a comprehensive review of the pharmacological activities,pharmacokinetic characteristics,and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy.We highlight new molecular targets of ginkgolide B,including nicotinamide adenine dinucleotide phosphate oxidases(NADPH oxidase),lectin-like oxidized LDL receptor-1(LOX-1),sirtuin 1(SIRT1),platelet-activating factor(PAF),proprotein convertase subtilisin/kexin type 9(PCSK9)and others.Finally,we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.

关键词： Cardiovascular disease Atherosclerosis Ginkgo biloba Ginkgolide B Endothelial dysfunction LOX-1 PCSK9 PAF-R antagonist

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Pharmacokinetics,distribution,and excretion of sodium oligomannate,a recently approved anti-Alzheimer's disease drug in China

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Journal of Pharmaceutical Analysis 2022年第1期12卷 145-155页

作者： jiaojiao lu Qiongqun Pan Jieqiang Zhou Yan Weng Kaili Chen Lv Shi Guanxiu Zhu Chunlin Chen Liang Li Meiyu Geng Zhenqing Zhang Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases College of Pharmaceutical SciencesSoochow UniversitySuzhouJiangsu215021China Shanghai Green Valley Pharma.Corp. Shanghai201203China Medicilon Preclinical Research(Shanghai)LLC Shanghai201299China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China

The National Medical Products Administration has authorized sodium oligomannate for treating mild-to-moderate Alzheimer’s disease.In this study,an LC-MS/MS method was developed and validated to quantitate sodium oligomannate in different biomatrices.The plasma pharmacokinetics,tissue distribution,and excretion of sodium oligomannate in Sprague-Dawley rats and beagle dogs were systematically investigated.Despite its complicated structural composition,the absorption,distribution,metabolism,and excretion profiles of the oligosaccharides in sodium oligomannate of different sizes and terminal derivatives were indiscriminate.Sodium oligomannate mainly crossed the gastrointestinal epithelium through paracellular transport following oral administration,with very low oral bioavailability in rats(0.6%-1.6%)and dogs(4.5%-9.3%).Absorbed sodium oligomannate mainly resided in circulating body fluids in free form with minimal distribution into erythrocytes and major tissues.Sodium oligomannate could penetrate the blood-cerebrospinal fluid(CSF)barrier of rats,showing a constant area under the concentration-time curve ratio(CSF/plasma)of approximately 5%.The cumulative urinary excretion of sodium oligomannate was commensurate with its oral bioavailability,supporting that excretion was predominantly renal,whereas no obvious biliary secretion was observed following a single oral dose to bile duct-cannulated rats.Moreover,only 33.7%(male)and 26.3%(female)of the oral dose were recovered in the rat excreta within 96 h following a single oral administration,suggesting that the intestinal flora may have ingested a portion of unabsorbed sodium oligomannate as a nutrient.

关键词： Sodium oligomannate Alzheimer’s disease Pharmacokinetics LC-MS/MS Oligosaccharide

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Tuna dark muscle peptides modulate host iron metabolism in the intestine through the gut microbiota and ameliorate iron deficiency anemia

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Food Science and Human Wellness 2024年

作者： jiaojiao Han Jiayi Xiong Zhixiang Bai Yang Qin Chenyang lu Jun Zhou Ye Li Tinghong Ming Zhen Zhang Xiurong Su State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products Ningbo University School of Marine Science Ningbo University

Iron deficiency anemia (IDA) is a nutritional deficiency disease with a high incidence rate worldwide. Bioactive peptides are safe and effective， have multiple functions and can serve as potential candidates for alleviating IDA. In this study， the anti-anemia effects of tuna dark muscle peptides were explored in a diet-induced IDA mouse model. The results showed that tuna dark muscle peptides alleviated the IDA phenotype， oxidative stress and iron metabolism. In addition， tuna dark muscle peptides reversed gut microbiota dysbiosis in IDA mice. Furthermore， the transplanted fecal microbiota from tuna dark muscle peptide-treated mice also alleviated IDA symptoms and regulated iron metabolism and the gut microbiota， indicating that the anti-anemic effects were at least partially mediated by the gut microbiota. Thus， we identified a new and safe prebiotic material to alleviate IDA and provided ideas for the development of peptides. At the same time， these data also provided a theoretical basis for fecal microbiota transplantation (FMT) to alleviate IDA.

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Protective effect of marine animals hydrolysis-peptides on adjuvant-induced arthritis in mice by gut microbiota and SCFAs

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Food Science and Human Wellness 2024年

作者： Zhen Zhang Shasha Tang Ziyan Wang jiaojiao Han Jun Zhou Chenyang lu Bin Liu Xiaoling Sun Rongxian Yu Rixin Wang Xiurong Su School of Marine Science Ningbo University State Key Laboratory for Quality and Safety of Argo-products Ningbo University Vigor Technology Group

Marine fauna provides a plentiful repository of peptides and bioactive proteins. Peptides and proteins isolated from marine animals have been studied and applied in the development of food supplements， drugs， and cosmeceutical products because of their special bioactivities， such as anti-inflammatory and antioxidant effects This study focused on exploring the alleviating effects of five major marine animal-derived peptides (Apostichopus japonicus， Acaudina leucoprocta， Melanogrammus aeglefinus， Phascolosoma esculenta and Rhopilema esculentum) on adjuvant-induced arthritis (AIA). The treatment with five marine animals-derived peptides downregulated the expression levels of pro-inflammatory cytokines of IL-1β， IL-17 and TNF-α in the bones of the mice with AIA and alleviated the rough surface of bone tissues significantly. A. japonicus-treatment ameliorates inflammation by restoring NF-κB pathway in AIA mice. High-throughput sequencing of the gut microbiota based on 16S rRNA sequencing revealed that A. japonicus peptide-treated AIA mice showed alterations and imbalance of intestinal flora and an increased abundance of Lactobacillus and Clostridium. Furthermore， metabolomic analysis showed that the level of SCFAs in the feces was enhanced to different degrees in mice treated with five major marine animal-derived peptides. Taken together， we propose that major marine animal-derived peptides can alleviate arthritis by improving the imbalance in the gut flora and increasing SCFA production to varying degrees.

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