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Gut liver brain axis in diseases:the implications for therapeutic interventions

Signal Transduction and Targeted Therapy 2024年第1期9卷 79-104页

作者： Mengyao Yan Shuli Man Benyue Sun Long Ma Lanping Guo Luqi Huang Wenyuan Gao State key laboratory of Food Nutrition and Safety Key Laboratory of Industrial MicrobiologyMinistry of EducationTianjin Key Laboratory of Industry MicrobiologyNational and Local United Engineering Lab of Metabolic Control Fermentation TechnologyChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal ChemistryCollege of BiotechnologyTianjin University of Science&Technology300457 TianjinChina National Resource Center for Chinese Materia Medica China Academy of Chinese Medical Sciences100700 BeijingChina tianjin key laboratory for Modern drug delivery&high-efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityWeijin Road300072 TianjinChina

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract,liver,and nervous systems.In the past few decades,breakthrough progress has been made in the gut liver brain axis,mainly through understanding its formation mechanism and increasing treatment strategies.In this review,we discuss various complex networks including barrier permeability,gut hormones,gut microbial metabolites,vagus nerve,neurotransmitters,immunity,brain toxic metabolites,β-amyloid(Aβ)metabolism,and epigenetic regulation in the gut-liver-brain axis.Some therapies containing antibiotics,probiotics,prebiotics,synbiotics,fecal microbiota transplantation(FMT),polyphenols,low FODMAP diet and nanotechnology application regulate the gut liver brain axis.Besides,some special treatments targeting gut-liver axis include farnesoid X receptor(FXR)agonists,takeda G protein-coupled receptor 5(TGR5)agonists,glucagon-like peptide-1(GLP-1)receptor antagonists and fibroblast growth factor 19(FGF19)analogs.Targeting gut-brain axis embraces cognitive behavioral therapy(CBT),antidepressants and tryptophan metabolism-related therapies.Targeting liver-brain axis contains epigenetic regulation and Aβmetabolism-related therapies.In the future,a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases.

关键词： metabolism therapeutic immunity

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Synergistic effects of three traditional herbs green tea,mulberry leaf and corn silk on glucose uptake level of L6 myoblasts and the hypoglycemic mechanism

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Traditional Medicine Research 2024年第7期9卷 1-12页

作者： Jing-Na Zhou Ming-Yue Li Ting-Ting Zhang Jing-Yang Lu Min Zhang Peng-Wei Zhuang Hai-Xia Chen tianjin key laboratory for Modern drug delivery&high-efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityTianjin 300072China. School of Food Science and Bioengineering Tianjin Agricultural UniversityTianjin 300384China. State key laboratory of Nutrition and Safety Tianjin University of Science&TechnologyTianjin 300457China. Haihe laboratory of Modern Chinese Medicine Chinese Materia Medica CollegeTianjin University of Traditional Chinese MedicineTianjin 301617China.

Background:Green tea,mulberry leaf and corn silk are traditional herbs used in the prevention and treatment of diabetes in China for a long time,but their synergistic hypoglycemic effects and mechanisms remain unclear.Methods:The effective components of green tea,mulberry leaf and corn silk were extracted and enriched.Mixture design of experiments was used to study the influences of different combinations on the cell viability and glucose uptake level of L6 myoblasts,so as to determine the optimal synergistic hypoglycemic combination.The possible hypoglycemic mechanism of the optimal synergistic combination was explored by cytotoxicity assay,glucose uptake assay,and western blot.Results:Three polyphenol enrichment fractions of the herbs,30%ethanol elution fraction of green tea(GT),50%ethanol elution fraction of mulberry leaf(ML)and 60%ethanol elution fraction of corn silk(CS)were obtained.The antioxidant activities of GT-30%,ML-50%and CS-60%were superior to those of crude extracts,and showed strong potential inα-amylase andα-glucosidase inhibition activities.The optimal synergistic combination of crude extracts G7(crude extract of green tea:crude extract of mulberry leaf:crude extract of corn silk=1:5:3),polyphenol enrichment fractions R3(GT-30%:ML-50%:CS-60%=1:7:1)and monomers X2(epigallocatechin gallate:morusin:formononetin=3:1:2)were selected,respectively.G7,R3,and X2 showed promoting effects on the cell viability and glucose uptake of L6 myoblasts within the detected concentration range.In addition,G7,R3,and X2 could increase the expression levels of p-PI3K/PI3K and p-Akt/Akt in L6 myoblasts,and promote the translocation of Glut4,but G7 and R3 showed more significant effects.Conclusion:The synergistic hypoglycemic effects of green tea,mulberry leaf and corn silk had the characteristics of multiple-components and multiple-targets with p-PI3K/PI3K,p-Akt/Akt and the translocation of Glut4 signal pathways involved.The three traditional herbs might have the potential to be combined used for the prevention and trea

关键词： green tea mulberry leaf corn silk synergistic effect type 2 diabetes mellitus mechanism

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Organic thin-film transistors and related devices in life and health monitoring

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Nano Research 2024年第2期17卷 426-444页

作者： Chenfang Sun Tie Wang tianjin key laboratory of drug Targeting and Bioimaging Life and Health Intelligent Research InstituteTianjin University of TechnologyTianjin 300384China

The early determination of disease-related biomarkers can significantly improve the survival rate of patients.Thus,a series of explorations for new diagnosis technologies,such as optical and electrochemical methods,have been devoted to life and health monitoring.Organic thin-film transistor(OTFT),as a state-of-the-art nano-sensing technology,has attracted significant attention from construction to application owing to the merits of being label-free,low-cost,facial,and rapid detection with multi-parameter responses.Nevertheless,interference from non-specific adsorption is inevitable in complex biological samples such as body liquid and exhaled gas,so the reliability and accuracy of the biosensor need to be further improved while ensuring sensitivity,selectivity,and stability.Herein,we overviewed the composition,mechanism,and construction strategies of OTFTs for the practical determination of disease-related biomarkers in both body fluids and exhaled gas.The results show that the realization of bio-inspired applications will come true with the rapid development of high-effective OTFTs and related devices.

关键词： organic thin-film transistors biosensors biomarkers organic bioelectronics organic semiconductors healthcare

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Discovery of Novel Anthranilic Diamide Derivatives Bearing Sulfoximine Group as Potent Insecticide Candidates

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Chemical Research in Chinese Universities 2024年第1期40卷 96-108页

作者： ZHANG Hongyuan PENG Jinmin ZHONG Yuanhan CHEN Yue WANG Qing Haditullah HADIATULLAH XIE Weibin XIONG Lixia YUCHI Zhiguang LIU Jingbo LI Yuxin State key laboratory of Elemento-Organic Chemistry College of ChemistryNankai UniversityTianjin300071P.R.China Nankai University&Cangzhou Bohai New Area Institute of Green Chemical Engineering Changzhou062550P.R.China College of Horticulture and Landscape Architecture Tianjin Agricultural UniversityTianjin300392P.R.China tianjin key laboratory for Modern drug delivery and high-efficiency Collaborative Innovation Center of Chemical Science and EngineeringSchool of Pharmaceutical Science and TechnologyTianjin UniversityTianjin300072P.R.China

The fall armyworm,Spodoptera frugiperda(S.frugiperda),represents the most resistant insect species and poses serious threat to grain yield.Chlorantraniliprole(CHL),which targets the ryanodine receptors(RyRs)in insects,has demonstrated the efficacy in controlling S.frugiperda.Nevertheless,this has led to emerging resistance in several countries.To counter this resistance,a viable approach involves the development of novel compounds that bind against RyRs via distinct binding sites or modes.In this study,a series of 22 novel anthranilic diamide derivatives was designed and synthesized,and their insecticidal activities were evaluated.Most of these derivatives showed moderate to good insecticidal activity against S.frugiperda and Mythimna separata.Time-lapse fluorescence measurements of endoplasmic reticulum luminal calcium revealed that most derivatives elicited cellular responses similar as CHL when assessed on HEK293 cells expressing S.frugiperda ryanodine receptors(SfRyRs).The mode of action of compound 13a was studied and verified on the isolated neurons by calcium imaging technique.Finally,molecular docking analysis was employed to predict the binding mechanism of compound 13a against SfRyRs.Overall,these novel diamide derivatives hold promise as a valuable resource for guiding the future design of insecticidal compounds targeting RyRs.

关键词： Anthranilic diamide derivative Sulfoximine Spodoptera frugiperda Mode of action Molecular docking

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Progress on Bionic Textured Cutting Tools:A Review and Prospects

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Journal of Bionic Engineering 2024年第1期21卷 19-55页

作者： Hong Wei Guangjun Chen Zhuang Chen Zhiwei Yu Jiashuai Huang tianjin key laboratory of high Speed Cutting and Precision Processing Tianjin 300222China School of Mechanical Engineering Tianjin University of Technology and EducationTianjin 300222China

Cutting tools are known as the“productivity”of the manufacturing industry,which affects the production efficiency and quality of the workpiece,and has become the focus of research and attention in academia and industry.However,traditional cutting tools often suffer from adhesion or wear during the cutting process,which considerably reduces the cutting efficiency and service life of the tools,and makes it difficult to meet current production requirements.To solve the above problems,scholars have introduced bionics into the tool’s design,applying the microscopic structure of the biological surface to the tool surface to alleviate the tool’s failure.This paper mainly summarizes the research progress of bionic textured cutting tools.Firstly,categorize whether the bionic texture design is inspired by a single organism or multiple organisms.Secondly,it is discussed that the non-smooth surface of the biological surface has five characteristics:hydrophilic lubricity,wear resistance,drag reduction and hydrophobicity,anti-adhesion,and arrangement,and the non-smooth structure of these different characteristics are applied to the surface of the tool is designed with bionic texture.Furtherly,the cutting performance of bionic textured cutting tools is discussed.The anti-friction and wear-resisting mechanism of bionic textured cutting tools is analyzed.Finally,some pending problems and perspectives have been proposed to provide new inspirations for the design of bionic textured cutting tools.

关键词： Bionic textured cutting tools Biological microstructure characteristics Cutting performance Anti-friction and wear-resisting mechanism

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Fine-tuning the activation behaviors of ternary modular cabazitaxel prodrugs for efficient and on-target oral anti-cancer therapy

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 188-203页

作者： Mingyang Zhang Yifan Miao Can Zhao Tong Liu Xiyan Wang Zixuan Wang Wenxin Zhong Zhonggui He Chutong Tian Jin Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China key laboratory of Advanced drug delivery Systems of Zhejiang Province Hangzhou 310058China Joint International Research laboratory of Intelligent drug delivery Systems Ministry of EducationShenyang 110016China Liaoning Provincial Institute of drug Inspection and Testing Shenyang 110036China

The disulfide bond plays a crucial role in the design of anti-tumor prodrugs due to its exceptional tumor-specific redox responsiveness. However, premature breaking of disulfide bonds is triggered by small amounts of reducing substances (e.g., ascorbic acid, glutathione, uric acid and tea polyphenols) in the systemic circulation. This may lead to toxicity, particularly in oral prodrugs that require more frequent and high-dose treatments. Fine-tuning the activation kinetics of these prodrugs is a promising prospect for more efficient on-target cancer therapies. In this study, disulfide, steric disulfide, and ester bonds were used to bridge cabazitaxel (CTX) to an intestinal lymph vessel-directed triglyceride (TG) module. Then, synthetic prodrugs were efficiently incorporated into self-nanoemulsifying drug delivery system (corn oil and Maisine CC were used as the oil phase and Cremophor EL as the surfactant). All three prodrugs had excellent gastric stability and intestinal permeability. The oral bioavailability of the disulfide bond-based prodrugs (CTX-(C)S-(C)S-TG and CTX-S-S-TG) was 11.5- and 19.1-fold higher than that of the CTX solution, respectively, demonstrating good oral delivery efficiency. However, the excessive reduction sensitivity of the disulfide bond resulted in lower plasma stability and safety of CTX-S-S-TG than that of CTX-(C)S-(C)S-TG. Moreover, introducing steric hindrance into disulfide bonds could also modulate drug release and cytotoxicity, significantly improving the anti-tumor activity even compared to that of intravenous CTX solution at half dosage while minimizing off-target adverse effects. Our findings provide insights into the design and fine-tuning of different disulfide bond-based linkers, which may help identify oral prodrugs with more potent therapeutic efficacy and safety for cancer therapy.

关键词： Steric disulfide bond Triglyceride-like pr odrugs Cabazitaxel Lymphatic transport Oral chemotherapy

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Effect of microstructure on lipolysis behavior of milk fat globules during gastrointestinal digestion

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Food Science and Human Wellness 2024年

作者： Xinyun Zhou Ting Guo Chen Chen Hadiatullah Hadiatullah Yunping Yao Changmo Li Xingguo Wang State key laboratory of Food Nutrition and Safety key laboratory of Food Nutrition and Safety Ministry of Education College of Food Science and Engineering tianjin University of Science & Technology tianjin key laboratory for Modern drug delivery & high-efficiency Collaborative Innovation Center of Chemical Science and Engineering School of Pharmaceutical Science and Technology tianjin University Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province National Engineering Research Center for Functional Food School of Food Science and Technology Jiangnan University

Milk fat globules (MFG) are the primary source of energy and functional factor in dairy-based products. To evaluate the suitability of commercial MFG substitutes for infant and adult consumers， the lipolysis properties and regulatory factors in digesting bovine， caprine， and human MFG were compared. The lipolysis kinetic models of bovine and caprine MFG are comparable， with bovine MFG displaying the highest degree of lipolysis (50.21%) during gastric digestion in infants， resulting in the production short-chain saturated fatty acids. Caprine MFG has a high rate of lipolysis due to its weak phospholipid-glycoprotein layer， which is prominent in both infants’ and adults’ digestion. The effects of consuming bovine and caprine MFG for adults are comparable in terms of lipolysis properties and nutritional value of fatty acid. After gastrointestinal digestion， human MFG has the highest digestibility (93.98%). The advantages of human MFG include its phospholipid structure， exogenous lipase， and lipolysis-regulating proteins. This study provides recommendation for the selection of milk fat substitutes and improvements in commercial dairy.

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Constructing porous ZnFC-PA/PSF composite spheres for highly efficient Cs^(+) removal

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Journal of Environmental Sciences 2024年第9期143卷 126-137页

作者： Senjian Han Chao Gao Wenfeng Yan Yafei Guo Shiqiang Wang Tianlong Deng College of Marine and Environmental Sciences Tianjin University of Science and TechnologyTianjin 300457China key laboratory of Marine Resource Chemistry and Food Technology Ministry of EducationTianjin 300457China

Radioisotope leaking from nuclear waste has become an intractable problem due to its gamma radiation and strong water solubility.In this work,a novel porous ZnFC-PA/PSF composite sphere was fabricated by immobilization of ferrocyanides modified zinc phytate into polysulfone(PSF)substrate for the treatment of Cs-contaminated water.The maximum adsorption capacity of ZnFC-PA/PSF was 305.38 mg/g,and the removal efficiency of Cs+was reached 94.27%within 2 hr.The ZnFC-PA/PSF presented favorable stability with negligible dissolution loss of Zn^(2+)and Fe^(2+)(high-selectivity towards Cs+(K_(d)=2.24×10^(4)mL/g)even in actual geothermal water.The adsorption mechanism was inferred to be the ion-exchange between Cs^(+)and K^(+).What’s more,ZnFC-PA/PSF worked well in the fixed-bed adsorption(E=91.92%),indicating the application potential for the hazardous Cs^(+)removal from wastewater.

关键词： Adsorption Cesium Metal ferrocyanide Composite adsorbent

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Expression of cyclin-dependent kinase 9 is positively correlated with the autophagy level in colon cancer

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 314-330页

作者： Lei Zheng Jia Lu Da-Lu Kong Department of Colorectal Cancer Surgery National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of Infection Management National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China

BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely studied.CDK9,a key regulator of transcription,may influence the occurrence and progression of CRC.The expression of auto-phagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in CRC.Under normal physiological conditions,autophagy can inhibit tumorigenesis,but once a tumor forms,autophagy may promote tumor growth.Therefore,understanding the relationship between autophagy and cancer,partic-ularly how autophagy promotes tumor growth after its formation,is a key motivation for this research.AIM To investigate the relationship between CDK9 expression and autophagy in CRC,assess differences in autophagy between left and right colon cancer,and analyze the associations of autophagy-related genes with clinical features and prognosis.METHODS We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of CDK9.We also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma tissues.RESULTS The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer,and autophagy might be involved in the occurrence of chemotherapy resistance.Further analysis of the rela-tionship between the expression of autophagy-related genes CDK9,ABCG2,and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal cancer.CONCLUSION This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.

关键词： Autophagy Tumorigenesis Tumor tissue Paracarcinoma tissue Expression Left/right colon cancer

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Förster resonance energy transfer reveals phillygenin and swertiamarin concurrently target AKT on different binding domains to increase the anti-inflammatory effect

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Chinese Chemical Letters 2024年第5期35卷 207-212页

作者： Xiaoyao Ma Jinling Zhang Ge Fang He Gao Jie Gao Li Fu Yuanyuan Hou Gang Bai State key laboratory of Medicinal Chemical Biology College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjin 300000China College of Life Health Dalian UniversityDalian 116622China Dalian Fusheng Pharmaceutical Co. Ltd.Dalian 116000China

The clinical benefit of combination therapy is significant,but it is not easy to define the mechanism of complexity and diversity.Previous studies illustrate that phillygenin(Phi)binds in the allosteric inhibit pocket of protein kinase B(AKT),and swertiamarin(Swe)acts on the pleckstrin homology(PH)domain of AKT.However,the combined synergistic effect of relieving the inflammatory response has yet to be elucidated.Based on high sensitivity,specificity and fast-responsibility fluorescent sensors,the Förster resonance energy transfer(FRET)technique offers a route to provide clear insights into physiological and pathological processes.In the study,molecular docking,the fluorescent probes of Phi and Swe for FRET were designed and synthesized.FRET analysis shown that Swe and Phi concurrently acted on the PH domain and allosterically inhibited pocket of AKT,respectively.The combination of Swe and Phi significantly increased the heat stability of AKT and decreased protease-induced degeneration.In lipopolysaccharides(LPS)-induced mice and cells,the combination arrested AKT activation,nuclear factor kappa-B(NF-κB)phosphorylation,and the expression of tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-8.In conclusion,FRET revealed Phi and Swe concurrently targeted AKT on different domains and the combination of Phi and Swe enhanced the anti-inflammatory effect.

关键词： FRET Swertiamarin Phillygenin AKT Anti-inflammation Combinatorial drug

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