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Salted egg white derived-peptides VF-4 and DR-8 improve DSS-induced colitis in mice by inhibiting NF-κB/MAPK/PI3K-AKT signaling pathways and modulating gut microbiota composition

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food Science and Human Wellness 2024年

作者： Na Zhou Na Wu Yao Yao Shuping Chen Mingsheng Xu Zhongping Yin Yan Zhao Yonggang Tu jiangxi key laboratory of natural products and functional food jiangxi Agricultural University Agricultural products Processing and Quality Control Engineering laboratory of jiangxi jiangxi Agricultural University jiangxi Experimental Teaching Demonstration Center of Agricultural products Storage and Processing Engineering jiangxi Agricultural University

Inflammation underlies many chronic diseases， and inflammatory bowel disease (IBD) is a condition characterized by long-term inflammation of the gut. Egg whites have been shown to contain many beneficial active substances. Therefore， we obtained two peptides from salted egg white: Val-Val-His-Phe (VF-4) and Asp-Thr-Gln-Ala-Met-Pro-Phe-Arg (DR-8). The sodium dextran sulfate (DSS)-induced mice colitis model was used to evaluate its regulatory effect on colitis in vivo. The results showed that VF-4 and DR-8 improved the clinical symptoms of DSS-induced colitis， attenuated colon tissue damage， inhibited the activation of NF-κB/MAPK/PI3K-AKT signaling pathways， and inhibited the expression of inflammatory cytokines. 16S rRNA gene sequencing showed that VF-4 and DR-8 administration increased the relative abundance of intestinal beneficial bacteria including Lactobacillus， Blautia， and down-regulated the relative abundance of inflammation-related bacteria including Acinetobacter， Lachnospiraceae＿NK4A136＿group， Klebsiella. Moreover， the degree of correlation between pro-inflammatory cytokines and microbiota was as follows: IL-6 > TNF-α > IL-1β > IFN-γ. In conclusion， this study suggests that salted egg white peptides VF-4 and DR-8 have a significant anti-inflammatory effect in vivo. It also provides a strategy for the treatment of inflammatory bowel disease and a new way for the high-value utilization of salted egg white.

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Comprehensive insights:unraveling the mechanisms of gut commensals in glucose metabolism regulation

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Science China(Life Sciences) 2024年第2期67卷 414-417页

作者： Zhipeng Li Qixing Nie Shao-Ping Nie State key laboratory of food Science and Resources China-Canada Joint Lab of Food Science and Technology(Nanchang)Key Laboratory of Bioactive Polysaccharides of Jiangxi ProvinceNanchang UniversityNanchang 330047China

The prevalence of type 2 diabetes(T2D)has escalated to a global epidemic,garnering widespread concern.Tremendous research utilizing germ-free(GF)mice,antibiotic treatments,and fecal microbiota transplantation approaches has established the critical role of gut microbiota in modulating glucose metabolism.The microbiota interacts with diets and the mucosal immune system,influencing intestinal permeability and the penetration of microbial products.

关键词： metabolism utilizing insight

Effects of Rosa roxburghii&edible fungus fermentation broth on immune response and gut microbiota in immunosuppressed mice

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food Science and Human Wellness 2024年第1期13卷 154-165页

作者： Dechang Xu Jielun Hu Yadong Zhong Yanli Zhang Wenting Liu Shaoping Nie Mingyong Xie State key laboratory of food Science and Technology China-Canada Joint Laboratory of Food Science and Technology(Nanchang)Key Laboratory of Bioactive Polysaccharides of Jiangxi ProvinceNanchang UniversityNanchang 330047China

With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.

关键词： Fermented foods Immunosuppressed mice Immune response Gut microbiota Short-chain fatty acids

A multi-enzymatic cascade reaction for the synthesis of bioactive C-oligosaccharides

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Chinese Chemical Letters 2024年第6期35卷 451-455页

作者： Kebo Xie Qian Zhang Fei Ye Jungui Dai State key laboratory of Bioactive Substance and Function of natural Medicines CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs and NHC Key Laboratory of Biosynthesis of Natural ProductsInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

C-Oligosaccharides are rare in nature and possess diverse bioactivities.However,their chemical synthesis faces many challenges.In this work,enzymatic introduction of C-linked sugar chains to target aglycones was successfully achieved by multi-enzymatic cascade reactions.A C-glycosyltransferase from Aloe barbadensis was employed to introduce the first C-linked glucose and then a cyclomaltodextrin glucanotransferase from Bacillus licheniformis was used to extend the sugar chain.A total of twenty C-oligosaccharides with 2-6 sugars were synthesized from scale-up reactions and exhibited good water solubility and sodium-dependent glucose transporter 2(SGLT2)inhibitory activity.Furthermore,a glucoamylase was used to control the length of the sugar chain and the C-maltosides were efficiently synthesized.These findings not only expanded the structural diversity of C-oligosaccharides,but also provided a strategy for the modification of C-glycoside drugs to improve the druggability.

关键词： C-Oligosaccharides C-Glycosyltransferase Cyclomaltodextrin glucanotransferase Glucoamylase Enzymatic synthesis SGLT2 inhibitory activity

A fungal CYP from Beauveria bassiana with promiscuous steroid hydroxylation capabilities

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Chinese Chemical Letters 2024年第5期35卷 218-222页

作者： Yu Peng Yue Wang Tian-Jiao Chen Jing-Jing Chen Jin-Ling Yang Ting Gong Ping Zhu State key laboratory of Bioactive Substance and Function of natural Medicines NHC Key Laboratory of Biosynthesis of Natural ProductsCAMS Key Laboratory of Enzyme and Biocatalysis of Natural DrugsInstitute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Hydroxylation of steroid core is critical to the synthesis of steroid drugs.Direct sp^(3) C-H hydroxylation is challenging through chemical catalysis,alternatively,fungal biotransformation offers a possible solution to this problem.However,mining and metabolic engineering of cytochrome P450 monooxygenases(CYPs)is usually regarded as a more eco-friendly and efficient strategy.Herein,we report the mining and identification of a new steroid CYP(CYP68BE1)from Beauveria bassiana by transcriptomics,heterologous expression,in vivo and in vitro functional characterization.The catalytic promiscuity of CYP68BE1 was explored,and CYP68BE1 showed promiscuously and catalytically versatile,which is qualified for monohydroxylation on C11α,C1α,C6βand dihydroxylation on C1β,11αand C6β,11αof six steroids,leading to the production of key steroid intermediates required in the industrial synthesis of some indispensable steroid drugs.Molecular dynamics simulations were performed,revealing the molecular basis of different binding orientations of CYP68BE1 with different substrates.The discovery of CYP68BE1 offers a promising biocatalyst for enriching the steroid structural and functional diversity,which also can be applied to biosynthesize valuable steroid drug intermediates.

关键词： Fungal CYPs Steroid hydroxylase Beauveria bassiana Promiscuous biocatalyst Molecular dynamics

Phenylhydrazone anions excitation for the photochemical carbonylation of aryl iodides with aldehydes

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Chinese Chemical Letters 2024年第4期35卷 346-351页

作者： Lei Shen Yang Zhang Linlin Zhang Chuanwang Liu Zhixian Ma Kangjiang Liang Chengfeng Xia key laboratory of Medicinal Chemistry for natural Resource Ministry of EducationYunnan Provincial Center for Research&Development of Natural ProductsSchool of PharmacyYunnan UniversityKunming 650500China

Spectroscopic investigations discovered that the in-situ generated phenylhydrazone anion was significantly bathochromically shifted to visible light region for photoactivation under irradiation. The photoexcited phenylhydrazone anion was potential to reduce aryl iodides via single electron transfer process for the subsequent radical chain reaction. A redox-neutral photochemical carbonylation of aryl iodides was developed on basis of the special spectroscopic features of phenylhydrazone anion. This protocol provided a convenient and efficient synthetic tool for accessing carbonylation products under redox neutral conditions without the need of transition-metals.

关键词： Organic anion Hydrazone Carbonylation Visible light Single electron transfer

Progress in approved drugs from natural product resources

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Chinese Journal of natural Medicines 2024年第3期22卷 195-211页

作者： LUO Zhongwen YIN Fucheng WANG Xiaobing KONG Lingyi State key laboratory of natural Medicines and Jiangsu key laboratory of Bioactive natural Product Research School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 211198China

natural products (NPs) have consistently played a pivotal role in pharmaceutical research, exerting profound impactson the treatment of human diseases. A significant proportion of approved molecular entity drugs are either directly derived from NPs orindirectly through modifications of NPs. This review presents an overview of NP drugs recently approved in China, the United States,and other countries, spanning various disease categories, including cancers, cardiovascular and cerebrovascular diseases, centralnervous system disorders, and infectious diseases. The article provides a succinct introduction to the origin, activity, development process, approval details, and mechanism of action of these NP drugs.

关键词： New drugs natural products Structural modification

Barley Protein LFBEP-C1 from Lactiplantibacillus plantarum dy-1 Fermented Barley Extracts by Inhibiting Lipid Accumulation in a Caenorhabditis elegans Model

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Biomedical and Environmental Sciences 2024年第4期37卷 377-386页

作者： ZHANG Jia Yan LIU Meng Ting LIU Yu Hao DENG Huan BAI Juan XIE Jian Hua XIAO Xiang School of food and Biological Engineering Jiangsu UniversityZhenjiang 212013JiangsuChina State key laboratory of food Science and Technology Nanchang UniversityNanchang 330047JiangxiChina

Objective This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans(C.elegans).Methods In this study,the fermented barley protein LFBEP-C1 was prepared and tested for its potential anti-obesity effects on C.elegans.The worms were fed Escherichia coli OP50(E.coli OP50),glucose,and different concentrations of LFBEP-C1.Body size,lifespan,movement,triglyceride content,and gene expression were analyzed.The results were analyzed using ANOVA and Tukey's multiple comparison test.Results Compared with the model group,the head-swing frequency of C.elegans in the group of LFBEP-C1 at 20μg/mL increased by 33.88%,and the body-bending frequency increased by 27.09%.This indicated that LFBEP-C1 improved the locomotive ability of C.elegans.The average lifespan of C.elegans reached 13.55 days,and the body length and width of the C.elegans decreased after LFBEP-C1 intake.Additionally,LFBEP-C1 reduced the content of lipid accumulation and triglyceride levels.The expression levels of sbp-1,daf-2,and mdt-15 significantly decreased,while those of daf-16,tph-1,mod-1,and ser-4 significantly increased after LFBEP-C1 intake.Changes in these genes explain the signaling pathways that regulate lipid metabolism.Conclusion LFBEP-C1 significantly reduced lipid deposition in C.elegans fed a high-glucose diet and alleviated the adverse effects of a high-glucose diet on the development,lifespan,and exercise behavior of C.elegans.In addition,LFBEP-C1 regulated lipid metabolism mainly by mediating the expression of genes in the sterol regulatory element-binding protein,insulin,and 5-hydroxytryptamine signaling pathways.

关键词： LFBEP-C1 Fermentation Protein Caenorhabditis elegans Lipid accumulation Signaling pathway

Single-cell profiling of the pig cecum at various developmental stages

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Zoological Research 2024年第1期45卷 55-68页

作者： Yan-Yuan Xiao Qing Zhang Fei Huang Lin Rao Tian-Xiong Yao Si-Yu Yang Lei Xie Xiao-Xiao Zou Li-Ping Cai Jia-Wen Yang Bin Yang Lu-Sheng Huang National key laboratory for Swine Genetic Improvement and Germplasm Innovation Ministry of Science and Technology of ChinaJiangxi Agricultural UniversityNanchangJiangxi 330045China

The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding of cellular diversity,functional heterogeneity,and their importance in intestinal tract development and disease.Although such profiling has been extensively conducted in humans and mice,the single-cell gene expression landscape of the pig cecum remains unexplored.Here,single-cell RNA sequencing was performed on 45572 cells obtained from seven cecal samples in pigs at four different developmental stages(days(D)30,42,150,and 730).Analysis revealed 12 major cell types and 38 subtypes,as well as their distinctive genes,transcription factors,and regulons,many of which were conserved in humans.An increase in the relative proportions of CD8^(+)T and Granzyme A(low expression)natural killer T cells(GZMA^(low)NKT)cells and a decrease in the relative proportions of epithelial stem cells,Tregs,RHEX^(+)T cells,and plasmacytoid dendritic cells(pDCs)were noted across the developmental stages.Moreover,the post-weaning period exhibited an up-regulation in mitochondrial genes,COX2 and ND2,as well as genes involved in immune activation in multiple cell types.Cell-cell crosstalk analysis indicated that IBP6^(+)fibroblasts were the main signal senders at D30,whereas IBP6^(−)fibroblasts assumed this role at the other stages.NKT cells established interactions with epithelial cells and IBP6^(+)fibroblasts in the D730 cecum through mediation of GZMA-F2RL1/F2RL2 pairs.This study provides valuable insights into cellular heterogeneity and function in the pig cecum at different development stages.

关键词： Single-cell RNA-seq Cecum Bama Xiang pigs Various developmental stages Cellular heterogeneity