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Genes & diseases 2024年第2期11卷 701-710页

作者： Minjie Wu Heng Dong Chao Xu Mengqing Sun Haojin Gao Fangtian Bu Jianxiang Chen College of Pharmacy and department of Hepatology Institute of Hepatology and Metabolic DiseasesThe Affiliated Hospital of Hangzhou Normal UniversityHangzhou Normal UniversityHangzhouZhejiang 311121China Laboratory of Cancer Genomics Division of Cellular and Molecular ResearchNational Cancer CentreSingapore 169610Singapore Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhouZhejiang 311121China

B-cell CLL/lymphoma 9(BCL9)is considered a key developmental regulator and a well-established oncogenic driver in multiple cancer types,mainly through potentiating the Wnt/β-catenin ***,increasing evidences indicate that BCL9 also plays multiple Wnt-independent ***,we summarized the updates of the canonical and non-canonical functions of BCL9 in cellular,physiological,or pathological ***,we also concluded that the targeted inhibitors disrupt the interaction ofβ-catenin with BCL9 reported recently.

关键词： BCL9 Development Immunity Multifaceted functions Therapeutic target Tumorigenesis

Mechanical regulation of lipid and sugar absorption by Piezo1 in enterocytes

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3576-3590页

作者： Tian Tao Qing Shu Yawen Zhao Wenying Guo Jinting Wang Yuhao Shi Shiqi Jia Hening Zhai Hui Chen Cunchuan Wang Geyang Xu department of Physiology School of MedicineJinan UniversityGuangzhou 510632China department of metabolic and Bariatric Surgery the First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Endoscopy center the First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Biotherapy center Cell-gene Therapy Translational Medicine Research Centerthe Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Key Laboratory of Viral Pathogenesis&Infection Prevention and Control(Jinan university) Ministry of EducationGuangzhou 510632China

Obesity is primarily caused by excessive intake as well as absorption of sugar and *** surge in distention pressure and intestinal motility accelerates the absorption of *** response of intestinal epithelial cells to mechanical stimulation is not fully ***1,a mechanosensitive ion channel,is widely expressed throughout the digestive ***,its function in intestinal nutrient absorption is not yet *** our study,excessive lipid deposition was observed in the duodenum of obese patients,while duodenal Piezo1-CaMKK2-AMPKa was decreased when compared to normal-weight *** high-fat diet condition,the Piezo1iKO mice exhibited abnormally elevated sugar and lipid absorption as well as severe lipid deposition in the duodenum and *** phenotypes were mainly caused by the inhibition of duodenal CaMKK2-AMPKa and the upregulation of SGLT1 and *** contrast,Yoda1,a Piezo1 agonist,was found to reduce intestinal lipid absorption in diet induced obese *** of Piezo1,stretch and Yoda1 inhibited lipid accumulation and the expression of DGAT2 and SGLT1,whereas knockdown of Piezo1 stimulated lipid accumulation and DGAT2 in Caco-2 *** study reveals a previously unexplored mechanical regulation of nutrient absorption in intestinal epithelial cells,which may shed new light on the therapy of obesity.

关键词： Piezo1 DGAT2 SGLT1 Lipid metabolism Obesity Mechanical sensing Intestinal lipid absorption Intestinal glucose absorption

When smoke meets gut:deciphering the interactions between tobacco smoking and gut microbiota in disease development

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Science China(Life Sciences) 2024年第5期67卷 854-864页

作者： Bo Chen Guangyi Zeng Lulu Sun Changtao Jiang center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third HospitalBeijing 100191China department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China center for Obesity and metabolic Disease Research School of Basic Medical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Women’s Reproductive Health and Fertility Promotion Peking UniversityBeijing 100191China department of Endocrinology and Metabolism Peking University Third HospitalBeijing 100191China

Tobacco smoking is a prevalent and detrimental habit practiced worldwide,increasing the risk of various diseases,including chronic obstructive pulmonary disease(COPD),cardiovascular disease,liver disease,and *** previous research has explored the detrimental health effects of tobacco smoking,recent studies suggest that gut microbiota dysbiosis may play a critical role in these *** tobacco smoke components,such as nicotine,are found in the gastrointestinal tract and interact with gut microbiota,leading to lasting impacts on host health and *** review delves into the ways tobacco smoking and its various constituents influence gut microbiota composition and *** also summarize recent advancements in understanding how tobacco smoking-induced gut microbiota dysbiosis affects host ***,this review introduces a novel perspective on how changes in gut microbiota following smoking cessation may contribute to withdrawal syndrome and the degree of health improvements in smokers.

关键词： tobacco smoking gut microbiota dysbiosis nicotine smoking cessation

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Bioengineered skin organoids:from development to applications

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Military Medical Research 2024年第3期11卷 449-466页

作者： Zi-Xuan Hong Shun-Tian Zhu Hao Li Jing-Zhi Luo Yu Yang Yang An Xi Wang Kai Wang department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China department of Hepatopancreatobiliary Surgery the Third Affiliated Hospital of Soochow UniversityChangzhou 213000JiangsuChina department of Plastic Surgery Peking University Third HospitalBeijing 100191China Clinical Stem Cell Research center Peking University Third HospitalBeijing 100191China State Key Laboratory of Cardiovascular Disease Fuwai HospitalBeijing 100037China Beijing Key Laboratory of metabolic Disorder Related Cardiovascular Disease Capital Medical UniversityBeijing 100050China

Signifcant advancements have been made in recent years in the development of highly sophisticated skin *** as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional(2D)systems and ethical *** inherent plasticity of skin organoids allows for their construction into physiological and pathological models,enabling the study of skin development and dynamic *** review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with ***,it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques,such as 3D printing and microfuidic *** review also summarizes and discusses the diverse applications of skin organoids in developmental biology,disease modelling,regenerative medicine,and personalized medicine,while considering their prospects and limitations.

关键词： Skin organoid Organoid generation Skin appendage Tissue engineering Disease modelling Regenerative medicine

Natural long-chain saturated fatty acids doped LNPs enabling spleen selective mRNA translation and potent cancer immunotherapy

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Nano Research 2024年第3期17卷 1804-1817页

作者： Fazhan Wang Meng Zhang Meiling Tian Jia Lou Longze Pan Xiaoke Gao Lijing Zhang Xiaohan Lou Linyu Zhu Yuqiao Sheng Ming Wang Rui Xue Wenjing Deng Shuai Shao Zhihai Qin Medical Research center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Translational Medical center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China department of Neuro-Intensive Care Unit The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Academy of Medical Sciences Zhengzhou UniversityZhengzhou 450052China

Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA *** expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA *** by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered *** the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA *** mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in *** with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma *** natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.

关键词： mRNA vaccine lipid nanoparticles spleen long-chain saturated fatty acid cancer immunotherapy

Inhibition of the RXRA-PPARα-FABP4 signaling pathway alleviates vascular cellular aging by an SGLT2 inhibitor in an atherosclerotic mice model

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Science China Life Sciences 2024年

作者： Weiwei Zhang Linghuan Wang Yujia Wang Yan Fang Ruihua Cao Zhiyi Fang Dong Han Xu Huang Zhenghui Gu Yingjie Zhang Yan Zhu Yan Ma Feng Cao department of Cardiology The Second Medical Centre Chinese PLA General Hospital National Clinical Research Center for Geriatric Diseases School of Medicine Nankai University department of Cardiology Beijing Friendship Hospital Capital Medical University

Atherosclerosis is the pathological cause of atherosclerotic cardiovascular disease （ASCVD）, which rapidly progresses during the cellular senescence. Sodium-glucose cotransporter 2 inhibitors （SGLT2is） reduce major cardiovascular events in patients with ASCVD and have potential antisenescence effects. Here, we investigate the effects of the SGLT2 inhibitor dapagliflozin on cellular senescence in atherosclerotic mice. Compared with ApoE-/-control mice treated with normal saline, those in the ApoE-/-dapagliflozin group, receiving intragastric dapagliflozin （0.1 mg kg-1d-1） for 14 weeks, exhibited the reduction in the total aortic plaque area （48.8%±6.6%vs. 74.6%±8.0%,Pmetabolic signaling pathways in dapagliflozin’s mechanism of ameliorating cellular aging and plaque progression. In vitro, dapagliflozin inhibited the expression of PPARα and its downstream signal FABP4, by which the accumulation of senescent cells in human aortic smooth muscle cells （HASMCs） was reduced under high-fat conditions. This effect was accompanied by a reduction in the intracellular lipid content and alleviation of oxidative stress. However, these beneficial effects of dapagliflozin could be reversed by the PPARα *** analysis and molecular docking simulations revealed that dapagliflozin might exert its effects by directly interacting with the RXRA protein, thereby influencing the expression of the PPARα signaling pathway. In conclusion, the cellular senescence of aortic smooth muscle cells is potentially altered by dapagliflozin through the suppression of the RXRA-PPARα-FABP4 s

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Homeostatic regulation of NAD(H)and NADP(H)in cells

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Genes & diseases 2024年第5期11卷 285-299页

作者： Luojun Chen Xiaoke Xing Pingfeng Zhang Lulu Chen Huadong Pei Cancer center Renmin Hospital of Wuhan UniversityWuhanHubei 430062China department of Oncology Georgetown Lombardi Comprehensive Cancer CenterGeorgetown University Medical CenterWashingtonDC 20057USA

Nicotinamide adenine dinucleotide(NAD^(+))/reduced NAD^(+)(NADH)and nicotinamide adenine dinucleotide phosphate(NADP^(+))/reduced NADP^(+)(NADPH)are essential metabolites involved in multiple metabolic pathways and cellular ***^(+)and NADH redox couple plays a vital role in catabolic redox reactions,while NADPH is crucial for cellular anabolism and antioxidant *** NAD(H)and NADP(H)homeostasis is crucial for normal physiological activity and is tightly regulated through various mechanisms,such as biosynthesis,consumption,recycling,and conversion between NAD(H)and NADP(H).The conversions between NAD(H)and NADP(H)are controlled by NAD kinases(NADKs)and NADP(H)phosphatases[specifically,metazoan SpoT homolog-1(MESH1)and nocturnin(NOCT)].NADKs facilitate the synthesis of NADP^(+)from NAD^(+),while MESH1 and NOCT convert NADP(H)into NAD(H).In this review,we summarize the physiological roles of NAD(H)and NADP(H)and discuss the regulatory mechanisms governing NAD(H)and NADP(H)homeostasis in three key aspects:the transcriptional and posttranslational regulation of NADKs,the role of MESH1 and NOCT in maintaining NAD(H)and NADP(H)homeostasis,and the influence of the circadian clock on NAD(H)and NADP(H)*** conclusion,NADKs,MESH1,and NOCT are integral to various cellular processes,regulating NAD(H)and NADP(H)*** of these enzymes results in various human diseases,such as cancers and metabolic ***,strategies aiming to restore NAD(H)and NADP(H)homeostasis hold promise as novel therapeutic approaches for these diseases.

关键词： MESH1 NAD(H) NADK NADP(H) Nocturnin

Serum 25-hydroxyvitamin D,genetic susceptibility,and the risk of incident type 2 diabetes:A prospective cohort in East China

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Chinese Medical Journal 2024年第8期137卷 972-979页

作者： Ying Sun Haojie Zhang Bin Wang Yuying Wang Chi Chen Yi Chen Yingli Lu Ningjian Wang Institute and department of Endocrinology and Metabolism Shanghai Ninth People’s HospitalShanghai JiaoTong University School of MedicineShanghai 200011China department of Endocrinology and Metabolism and department of Guideline and Rapid Recommendation Cochrane China CenterMAGIC China CenterChinese Evidence-Based Medicine CenterWest China HospitalSichuan UniversityChengduSichuan 610041China department of Endocrinology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China

Background:The serum vitamin D level varies widely by population,and studies have linked vitamin D levels with the risk of type 2 diabetes mellitus(T2DM).However,the relationship is inconsistent and the impact of vitamin D on T2DM among East Chinese adults is *** study aimed to investigate the association between serum 25-hydroxyvitamin D(25[OH]D)levels and the risk of T2DM and evaluated whether the association is modified by genetic ***:In the Survey on Prevalence in East China for metabolic diseases and Risk Factors(SPECT-China)cohort,1862 participants free of T2DM at baseline were included.A weighted genetic risk score was calculated with 28 variants associated with *** logistic models were used to examine the association of serum 25(OH)D and genetic risk with ***:After a 5-year follow-up,132 cases of T2DM were *** observed no significant association between quartiles of serum 25(OH)D and T2DM risk after multivariable adjustment(χ^(2)=0.571,P_(for trend)=0.426).Compared to those in the lowest quartile of 25(OH)D,the odds ratios(ORs)(95%confidence interval[CI])for participants with increased quartiles were 1.29(0.74-2.25),1.35(0.77-2.36),and 1.27(0.72-2.24),*** observed a positive association of glycated hemoglobin(HbA1c)with 25(OH)D at baseline(β=1.752,P=0.001)and after follow-up(β=1.385,P=0.003),and a negative association of ln conversion homeostasis model assessment(HOMA)-βwith 25(OH)D at baseline(β=-0.982,P=0.021).There was no significant interaction between 25(OH)D and diabetes genetic predisposition on the risk of T2DM(χ^(2)=2.710,P_(for interaction)=0.100).The lowest OR(95%CI)of T2DM was among participants with low genetic risk and the highest quartile of 25(OH)D(0.17[0.05-0.62]).Conclusion:Serum 25(OH)D may be irrelevant to the risk of incident T2DM among East Chinese adults regardless of genetic predisposition.

关键词： Vitamin D Diabetes mellitus,Type 2 Genetic predisposition to disease Prospective cohort Glycated hemoglobin SPECT-China

Weight change and all-cause and cause-specific mortality:A 25-year follow-up study

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Chinese Medical Journal 2024年第10期137卷 1169-1178页

作者： Huan Yang Jianbing Wang Xiaokun Wang Wanyi Sun Chenyunhao Tong Jinhu Fan Youlin Qiao Christian *** department of Cancer Epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China department of Public Health Zhejiang University School of MedicineNational Clinical Research Center for Children’s HealthHangzhouZhejiang 310058China metabolic Epidemiology Branch Division of Cancer Epidemiology and GeneticsNational Cancer InstituteRockvilleMD 20850USA

Background:Whether the dynamic weight change is an independent risk factor for mortality remains *** study aimed to examine the association between weight change and risk of all-cause and cause-specific mortality based on the Linxian Nutrition Intervention Trial(NIT)***:Body weight of 21,028 healthy residents of Linxian,Henan province,aged 40-69 years was measured two times from 1986 to *** events were prospectively collected up to *** maintenance group(weight changediseases)=1.21,95%CI:1.11-1.31,P<0.001),whereas subjects with weight gain≥5 kg had 11%(HR_(Cancer)=0.89,95%CI:0.79-0.99,P=0.033)lower risk of cancer mortality and 23%higher risk of stroke mortality(HR_(Stroke)=1.23,95%CI:1.12-1.34,P<0.001).For the change of weight status,both going from overweight to normal weight and becoming underweight within 5 years could increase the risk of total death(HR_(Overweight to normal)=1.18,95%CI:1.09-1.27;HR_(Becoming underweight)=1.35,95%CI:1.25-1.46)and cancer death(HR_(Overweight to normal)=1.20,95%CI:1.04-1.39;HR_(Becoming underweight)=1.44,95%CI:1.24-1.67),while stable overweight could increase the risk of total death(HR_(Stable overweight)=1.11,95%CI:1.05-1.17)and death from stroke(HR_(Stable overweight)=1.44,95%CI:1.33-1.56).Interaction effects were observed between age and weight change on cancer mortality,as well as between baseline BMI and weight change on all-cause,heart disease,and stroke mortality(all P_(

关键词： Weight change All-cause mortality Cancer Stroke Heart diseases Body mass index

NOX4 promotes tumor progression through the MAPK-MEK1/2-ERK1/2 axis in colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1421-1436页

作者： Yu-Jie Xu Ya-Chang Huo Qi-Tai Zhao Jin-Yan Liu Yi-Jun Tian Lei-Lei Yang Yi Zhang Biotherapy center and Cancer center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina department of Oncology Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityPeople’s Hospital of Henan UniversityZhengzhou 450003Henan ProvinceChina

BACKGROUND metabolic reprogramming plays a key role in cancer progression and clinical outcomes;however,the patterns and primary regulators of metabolic reprogramming in colorectal cancer(CRC)are not well *** To explore the role of nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)in promoting progression of *** We evaluated the expression and function of dysregulated and survival-related metabolic genes using Gene Ontology and Kyoto Encyclopedia of Genes and *** clustering was used to cluster CRC based on dysregulated metabolic genes.A prediction model was constructed based on survival-related metabolic *** formation,migration,invasion,proliferation,apoptosis and clone formation was used to evaluate the biological function of NOX4 in *** sequencing was utilized to explore the alterations of gene expression NOX4 over-expression tumor *** vivo subcutaneous and lung metastasis mouse tumor model was used to explore the effect of NOX4 on tumor *** We comprehensively analyzed 3341 metabolic genes in CRC and identified three clusters based on dysregulated metabolic *** these genes,NOX4 was highly expressed in tumor tissues and correlated with worse *** vitro,NOX4 overexpression induced clone formation,migration,invasion,and stemness in CRC ***,RNA-sequencing analysis revealed that NOX4 overexpression activated the mitogen-activated protein kinase-MEK1/2-ERK1/2 signaling ***,a MEK1/2 inhibitor,abolished the NOX4-mediated tumor *** vivo,NOX4 overexpression promoted subcutaneous tumor growth and lung metastasis,whereas trametinib treatment can reversed the *** Our study comprehensively analyzed metabolic gene expression and highlighted the importance of NOX4 in promoting CRC metastasis,suggesting that trametinib could be a potential therapeutic drugs of CRC clinical therapy targeting NOX4.

关键词： Colorectal cancer metabolic reprogramming Metastasis Nicotinamide adenine dinucleotide phosphate oxidase 4 Mitogen-activated protein kinase signaling