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Genes & Diseases 2024年第3期11卷 26-29页

作者： Xiangyu Dong Yannian Gou Meichun Guo Jiamin Zhong Aohua Li Ailing Hao Wei Zeng Rex C.Haydon Hue H.Luu Russell R.Reid Tongchuan He Yan Xu Jiaming Fan Ministry of Education Key laboratory of Diagnostic Medicine And Department of Clinical BiochemistryCollege of Laboratory MedicineChongqing Medical UniversityChongqing 400016China molecular Oncology laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China laboratory of Craniofacial Suture biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Institute of Sports Medicine Beijing Key Laboratory of Sports InjuriesPeking University Third HospitalBejing 100191China

With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport *** for autologous stem cell-based therapies,allogeneic stem cell therapies and ex vivo genetically engineered cell therapies would require safe,efficient,and reliable cell preservation and transport methods.

关键词： transport methods simplified

CD36 promotes tubular ferroptosis by regulating the ubiquitination of FSP1 in acute kidney injury

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Genes & Diseases 2024年第1期11卷 449-463页

作者： Yixin Ma Lili Huang Zheng Zhang Pengfei Yang Qingsong Chen Xujia Zeng Fangyan Tan Chunxia Wang Xiongzhong Ruan Xiaohui Liao department of Nephrology The Second Affiliated HospitalChongqing Medical UniversityChongqing 400010China department of Cell biology and Genetics Chongqing Medical UniversityChongqing 400016China Centre for Nephrology Royal Free and University College Medical SchoolUniversity College LondonRoyal Free CampusRowland Hill StreetLondon NW32PFUnited Kingdom Centre for Lipid Research Key Laboratory of Molecular Biology on Infectious DiseasesMinistry of EducationChongqing Medical UniversityChongqing 400016China Kuanren laboratory of Translational Lipidology Centre for Lipid ResearchSecond Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

Reactive oxidative species(ROos)production-driven ferroptosis plays a role in acute kidney injury(Akl).However,its exact molecular mechanism is poorly *** receptor CD36 has important roles in oxidizing lipids,lipid accumulation,metabolic syndrome,and insulin resistance in chronic kidney disease,but its roles remain unexplored in *** present study investigated the role and mechanism of CD36 in regulating proximal tubular cell ferroptosis and *** expression of CD36 was found to be significantly up-regulated in AKI renal tissues and correlated with renal function,which might serve as an independent biomarker for AKl ***,in adult mice subjected to AKl,deletion of CD36(CD36-/-)induced tubular cell Ros accumulation,ferroptosis activation,and renal ***,combining LC-MS/MS,co-IP,and ubiquitination analyses revealed that CD36 could specifically bind to ferroptosis suppressor protein 1(FSP1)and regulate its ubiquitination at sites K16 and K24,leading to FSP1 degradation and progression of ferroptosis in *** present results emphasize a novel mechanism of CD36 in cisplatin-induced *** discovery of the special CD36 roles in promoting ferroptosis and AKI development by regulating the ubiquitination of FSP1 in proximal tubular cells may be potential therapeutic targets for ***,CD36 may play a key role in the progression of ***,targeting CD36 may provide a promising treatment option for AKI.

关键词： Acute kidney injury CD36 Ferroptosis FSP1 Ubiquitin-dependent degradation

HIV encephalopathy is contributed by macrophages and microglia

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Science China(Life Sciences) 2024年第4期67卷 836-838页

作者： Si-Meng Liu Man Li Chunhui Ma Chunying Liu An Lv Qing Li Yamei Niu Peng Wang Bo Huang Wei-Min Tong department of Pathology China Medical UniversityShenyang 110122China department of Pathology Institute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeNeuroscience CenterChinese Academy of Medical SciencesBeijing 100005China department of Pathology Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China molecular Pathology Research Center Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Center For Experimental Animal Research Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China department of Immunology and National Key laboratory of medical molecular biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100010China department of Biochemistry and molecular biology Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Dear Editor,Acquired immunodeficiency syndrome(AIDS),characterized by a significant decrease in the number of CD4^(+)T cells,causes a defective T cell immune response,which subsequently leads to various conditional pathogenic infections and tumors(Calmy et al.,2018;Seligmann et al.,1987).Neurological disorders have been reported in 70%–80%of patients with AIDS(Saylor et al.,2016)。

关键词： encephalopathy immunodeficiency

Gut microbial-host-isozymes are new targets for diseases

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Science China(Life Sciences) 2024年第7期67卷 1525-1527页

作者： Zhiwei Zhang Kai Wang Changtao Jiang department of Physiology and pathophysiology School of Basic Medical SciencesState Key Laboratory of Female Fertility PromotionCenter for Reproductive MedicinePeking UniversityBeijing 100191China Center for Obesity and Metabolic Disease Research School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China

Gut microbiota can interact with the host through lots of media including small molecular metabolites and proteins(Cani,2019;Fan and Pedersen,2021;Krautkramer et al.,2021).Recently,a new interaction pattern was identified,i.e.,gut microbiota can mimic the function of the host by producing a variety of enzymes with functions homologous to host enzymes.

关键词： diseases pattern

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Loss of LBP triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPβ-SCD activation in non-alcoholic fatty liver disease

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Zoological Research 2024年第1期45卷 79-94页

作者： Ya-Ling Zhu Lei-Lei Meng Jin-Hu Ma Xin Yuan Shu-Wen Chen Xin-Rui Yi Xin-Yu Li Yi Wang Yun-Shu Tang Min Xue Mei-Zi Zhu Jin Peng Xue-Jin Lu Jian-Zhen Huang Zi-Chen Song Chong Wu Ke-Zhong Zheng Qing-Qing Dai Fan Huang Hao-Shu Fang department of pathophysiology Anhui Medical UniversityHefeiAnhui 230032China laboratory Animal Research Center School of Basic Medical SciencesAnhui Medical UniversityHefeiAnhui 230032China department of Hepatobiliary Surgery First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China College of Animal Science and Technology Jiangxi Agricultural UniversityNanchangJiangxi 330045China

Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain ***,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP ***,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory *** total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD *** on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating *** study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.

关键词： Non-alcoholic fatty liver disease C/EBPβ Lipopolysaccharide-binding protein H3K27ac Integrative analysis Enhancer

High-fat diet impairs gut barrier through intestinal microbiota-derived reactive oxygen species

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Science China(Life Sciences) 2024年第5期67卷 879-891页

作者： Nianyi Zeng Fan Wu Junqi Lu Xiang Li Shaomei Lin Lang Zhou Zhongwei Wang Guangyan Wu Qingfa Huang Daowen Zheng Jie Gao Shan Wu Xiaojiao Chen Muxuan Chen Fanguo Meng Haitao Shang Yan He Peng Chen Hong Wei Zhuang Li Hongwei Zhou Microbiome Medicine Center Department of Laboratory MedicineZhujiang HospitalSouthern Medical UniversityGuangzhou 510282China department of Environmental Health Guangdong Provincial Key Laboratory of Tropical Disease ResearchSchool of Public Health and Tropical MedicineSouthern Medical UniversityGuangzhou 510515China Redox medical Center for Public Health Soochow UniversitySuzhou 215301China Precision Medicine Institute The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China department of pathophysiology Guangdong Provincial Key Laboratory of ProteomicsSchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China

Gut barrier disruption is a key event in bridging gut microbiota dysbiosis and high-fat diet(HFD)-associated metabolic ***,the underlying mechanism remains *** the present study,by comparing HFD-and normal diet(ND)-treated mice,we found that the HFD instantly altered the composition of the gut microbiota and subsequently damaged the integrity of the gut *** sequencing revealed that the HFD upregulates gut microbial functions related to redox reactions,as confirmed by the increased reactive oxygen species(ROS)levels in fecal microbiota incubation in vitro and in the lumen,which were detected using in vivo fluorescence *** microbial ROS-producing capability induced by HFD can be transferred through fecal microbiota transplantation(FMT)into germ-free(GF)mice,downregulating the gut barrier tight ***,mono-colonizing GF mice with an Enterococcus strain excelled in ROS production,damaged the gut barrier,induced mitochondrial malfunction and apoptosis of the intestinal epithelial cells,and exacerbated fatty liver,compared with other low-ROS-producing Enterococcus *** administration of recombinant high-stability-superoxide dismutase(SOD)significantly reduced intestinal ROS,protected the gut barrier,and improved fatty liver against the *** conclusion,our study suggests that extracellular ROS derived from gut microbiota play a pivotal role in HFD-induced gut barrier disruption and is a potential therapeutic target for HFD-associated metabolic diseases.

关键词： fatty liver disease gut microbiota gut barrier high-fat diet oxidative stress reactive oxygen species

Disulfiram:A novel repurposed drug for cancer therapy

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Chinese medical Journal 2024年第12期137卷 1389-1398页

作者： Min Zeng Baibei Wu Wenjie Wei Zihan Jiang Peiqiang Li Yuanting Quan Xiaobo Hu department of Biochemistry and molecular biology School of Basic MedicineHengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China The Key laboratory of Ecological Environment and Critical Human Diseases Prevention of Hunan Province department of Education Hengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China Institute of Biochemistry of Hengyang medical School University of South ChinaHengyangHunan 421001China

Cancer is a major global health *** therapeutic strategies can prolong patients’survival and reduce the costs of *** repurposing,which identifies new therapeutic uses for approved drugs,is a promising approach with the advantages of reducing research costs,shortening development time,and increasing efficiency and ***(DSF),a Food and Drug Administration(FDA)-approved drug used to treat chronic alcoholism,has a great potential as an anticancer drug by targeting diverse human *** studies show the antitumor effects of DSF,particularly the combination of DSF and copper(DSF/Cu),on a wide range of cancers such as glioblastoma(GBM),breast cancer,liver cancer,pancreatic cancer,and *** this review,we summarize the antitumor mechanisms of DSF/Cu,including induction of intracellular reactive oxygen species(ROS)and various cell death signaling pathways,and inhibition of proteasome activity,as well as inhibition of nuclear factor-kappa B(NF-κB)***,we highlight the ability of DSF/Cu to target cancer stem cells(CSCs),which provides a new approach to prevent tumor recurrence and ***,DSF/Cu inhibits several molecular targets associated with drug resistance,and therefore it is becoming a novel option to increase the sensitivity of chemo-resistant and radio-resistant *** of DSF/Cu may shed light on its improved application to clinical tumor treatment.

关键词： Disulfiram Aldehyde dehydrogenase Reactive oxygen species Proteasome activity Cancer stem cells Drug resistance

The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex C.Haydon Hue H.Luu Sherwin Ho Michael J.Lee Jason Strelzow Russell R.Reid Tong-Chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA molecular Oncology laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Clinical laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China laboratory of Craniofacial Suture biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

Effects of serum proteins on corrosion rates and product bioabsorbability of biodegradable metals

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Regenerative Biomaterials 2024年第1期3卷 132-148页

作者： Hongjie Zhang Xin Li Zehua Qu Wanqian Zhang Qunsong Wang Dinglingge Cao Yaoben Wang Xin Wang Yang Wang Lin Yu Jiandong Ding State Key laboratory of molecular Engineering of Polymers Department of Macromolecular ScienceFudan UniversityShanghai 200438China

Corrodible metals are the newest kind of biodegradable materials and raise a new problem of the corrosion ***,the removal of the precipitated products has been unclear and even largely ignored in ***,we find that albumin,an abundant macromolecule in serum,enhances the solubility of corrosion products of iron in blood mimetic Hank’s solution *** is universal for other main biodegradable metals such as magnesium,zinc and polyester-coated *** also influences corrosion rates in diverse trends in Hank’s solution and normal *** on quantitative study theoretically and experimentally,both the effects on corrosion rates and soluble fractions are interpreted by a unified mechanism,and the key factor leading to different corrosion behaviors in corrosion media is the interference of albumin to the Ca/P passivation layer on the metal *** work has illustrated that the interactions between metals and media macromolecules should be taken into consideration in the design of the next-generation metal-based biodegradable medical devices in the formulism of precision *** improved Hank’s solution in the presence of albumin and with a higher content of initial calcium salt is suggested to access biodegradable metals potentially for cardiovascular medical devices,where the content of calcium salt is calculated after consideration of chelating of calcium ions by albumin,resulting in the physiological concentration of free calcium ions.

关键词： biodegradable metal macromolecule albumin corrosion bioabsorbability iron polylactide magnesium zinc

Ionic liquids as the effective technology for enhancing transdermal drug delivery: Design principles, roles, mechanisms, and future challenges

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 38-51页

作者： Xuejun Chen Ziqing Li Chunrong Yang Degong Yang department of Pharmacy Shantou University Medical CollegeShantou 515041China Guangdong Provincial Key laboratory of Infectious Diseases and molecular Immunopathology Shantou University Medical CollegeShantou 515041China

Ionic liquids (ILs) have been proven to be an effective technology for enhancing drug transdermal absorption. However, due to the unique structural components of ILs, the design of efficient ILs and elucidation of action mechanisms remain to be explored. In this review, basic design principles of ideal ILs for transdermal drug delivery system (TDDS) are discussed considering melting point, skin permeability, and toxicity, which depend on the molar ratios, types, functional groups of ions and inter-ionic interactions. Secondly, the contributions of ILs to the development of TDDS through different roles are described: as novel skin penetration enhancers for enhancing transdermal absorption of drugs;as novel solvents for improving the solubility of drugs in carriers;as novel active pharmaceutical ingredients (API-ILs) for regulating skin permeability, solubility, release, and pharmacokinetic behaviors of drugs;and as novel polymers for the development of smart medical materials. Moreover, diverse action mechanisms, mainly including the interactions among ILs, drugs, polymers, and skin components, are summarized. Finally, future challenges related to ILs are discussed, including underlying quantitative structure-activity relationships, complex interaction forces between anions, drugs, polymers and skin microenvironment, long-term stability, and in vivo safety issues. In summary, this article will promote the development of TDDS based on ILs.

关键词： Transdermal drug delivery system Ionic liquid Quantitative structure-activity relationship Intermolecular interaction