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PDK1 promotes breast cancer progression by enhancing the stability and transcriptional activity of HIF-1α

Genes & Diseases 2024年第4期11卷 353-367页

作者： Yu Wei Dian Zhang He Shi Husun Qian Hongling Chen Qian Zeng Fangfang Jin Yan Ye Zuli Ou Minkang Guo Bianqin Guo Tingmei Chen key laboratory of clinical laboratory Diagnostics(Ministry of Education) College of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Chongqing key laboratory of translational Research for Cancer Metastasis and Individualized Treatment Chongqing University Cancer HospitalChongqing 400030China

Pyruvate dehydrogenase kinase 1(PDK1)phosphorylates the pyruvate dehydroge-nase complex,which inhibits its *** pyruvate dehydrogenase complex inhibits the tricarboxylic acid cycle and the reprogramming of tumor cell metabolism to glycolysis,which plays an important role in tumor *** study aims to elucidate how PDK1 pro-motes breast cancer *** found that PDK1 was highly expressed in breast cancer tissues,and PDK1 knockdown reduced the proliferation,migration,and tumorigenicity of breast cancer cells and inhibited the HIF-1α(hypoxia-inducible factor 1α)*** investigation showed that PDK1 promoted the protein stability of HIF-1αby reducing the level of ubiquitination of HIF-1α.The HIF-1αprotein levels were dependent on PDK1 kinase ***,HIF-1αphosphorylation at serine 451 was detected in wild-type breast cancer cells but not in PDK1 knockout breast cancer *** phosphorylation of HIF-1αat Ser 451 stabilized its protein levels by inhibiting the interaction of HIF-1αwith von Hippel-Lindau and prolyl hydroxylase *** also found that PDK1 enhanced HIF-1αtranscriptional *** summary,PDK1 enhances HIF-1αprotein stability by phosphorylating HIF-1αat Ser451 and promotes HIF-1αtranscriptional activity by enhancing the binding of HIF-1αto ***1 and HIF-1αform a positive feedback loop to promote breast cancer progression.

关键词： Breast cancer HIF-1α PDK1 Protein phosphorylation Transcriptional activity

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Di-PEGylated insulin:A long-acting insulin conjugate with superior safety in reducing hypoglycemic events

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2761-2772页

作者： Zhipeng Zeng Runcheng Tan Shi Chen Haolin Chen Zhijia Liu Lixin Liu Mingqiang Li Yongming Chen laboratory of Biomaterials and translational medicine Center for NanomedicineThe Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China School of Materials Science and Engineering Center of Functional BiomaterialsKey Laboratory of Polymeric Composite Materials and Functional Materials of Ministry of EducationSun Yat-sen UniversityGuangzhou 510275China

Although the discovery of insulin 100 years ago revolutionized the treatment of diabetes,its therapeutic potential is compromised by its short half-life and narrow therapeutic *** long-acting insulin analogs,such as insulin-polymer conjugates,are mainly used to improve pharmacokinetics by reducing renal ***,these conjugates are synthesized without sacrificing the bioactivity of insulin,thus retaining the narrow therapeutic index of native insulin,and exceeding the efficacious dose still leads to ***,we report a kind of di-PEGylated insulin that can simultaneously reduce renal clearance and receptor-mediated *** impairing the binding affinity to the receptor and the activation of the receptor,di-PEGylated insulin not only further prolongs the half-life of insulin compared to classical mono-PEGylated insulin but most importantly,increases its maximum tolerated dose *** target of long-term glycemic management in vivo has been achieved through improved pharmacokinetics and a high *** work represents an essential step towards long-acting insulin medication with superior safety in reducing hypoglycemic events.

关键词： Diabetes Insulin Therapeutic index Hypoglycemia PEGylation Receptor-mediated clearance Half-life Diabetic nephropathy

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The m^(6)A regulator KIAA1429 stabilizes RAB27B mRNA and promotes the progression of chronic myeloid leukemia and resistance to targeted therapy

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Genes & Diseases 2024年第2期11卷 993-1008页

作者： Fangyi Yao Fangmin Zhong Junyao Jiang Ying Cheng Shuai Xu Jing Liu Jin Lin Jing Zhang Shuqi Li Meiyong Li Yanmei Xu Bo Huang Xiaozhong Wang Jiangxi Province key laboratory of laboratory medicine Jiangxi Provincial Clinical Research Center for Laboratory MedicineDepartment of Clinical LaboratoryThe Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China

Chronic myeloid leukemia(CML)is a common adult *** the acute phase of the disease and the adverse effects of anti-cancer treatments can lead to a poor *** N6-methyladenine(m^(6)A)modification plays an important regulatory role in various physiological and pathological ***1429 is a known m^(6)A regulator,but the biological role of KIAA1429 in CML is *** this study,we observed that the m^(6)A levels and KIAA1429 expression were significantly up-regulated in patients with blast phase ***,KIAA1429 regulated the total level of RNA m^(6)A modification in the CML cells and promoted the malignant biological behaviors of CML cells,including proliferation,migration,and imatinib *** KIAA1429 in CML cells reduced the stability of RAB27B mRNA through the m^(6)A/YTHDF1 axis,consequently inhibiting CML proliferation and drug efflux,ultimately increasing the sensitivity of CML cells to ***,the knockdown of RAB27B also inhibited the proliferation and drug resistance of CML cells and promoted their ***,a recently developed anti-cancer agent,suppressed the expression of KIAA1429 and CML cell proliferation and promoted cell *** also inhibited the tumorigenesis of CML cells in *** combined use of rucaparib and imatinib enhanced the sensitivity of CML cells to *** study provides evidence that elevated KIAA1429 expression in the blast phase of CML enhances the stability of RAB27B mRNA through the m^(6)A/YTHDF1 axis to up-regulate RAB27B expression,thereby promoting CML *** exerts inhibitory effects on KIAA1429 expression and thus reduces CML progression.

关键词： Chronic myeloid leukemia KIAA1429 N6-methyladenine RAB27B Rucaparib YTHDF1

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Iridoids modulate inflammation in diabetic kidney disease: A review

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Journal of Integrative medicine 2024年第3期22卷 210-222页

作者： Tong-yi Zhou Na Tian Liu Li Rong Yu The First clinical College of Chinese medicine Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina Hunan Provincial key laboratory of translational Research in Traditional Chinese medicine Prescriptions and Zheng Changsha 410208Hunan ProvinceChina

In recent years,preclinical research on diabetic kidney disease (DKD) has surged to the forefront of scientific and clinical *** has become a pervasive complication of type 2 *** the complexity of its etiology and pathological mechanisms,current interventions,including drugs,dietary modifications,exercise,hypoglycemic treatments and lipid-lowering methods,often fall short in achieving desired therapeutic ***,primarily derived from the potent components of traditional herbs,have been the subject of long-standing *** data suggest that iridoids possess notable renal protective properties;however,there has been no summary of the research on their efficacy in the management and treatment of *** article consolidates findings from in vivo and in vitro research on iridoids in the context of DKD and highlights their shared anti-inflammatory activities in treating this ***,it explores how certain iridoid components modify their chemical structures through the regulation of intestinal flora,potentially bolstering their therapeutic *** review provides a focused examination of the mechanisms through which iridoids may prevent or treat DKD,offering valuable insights for future research endeavors.

关键词： Diabetic kidney disease Iridoids Gut-kidney axis Traditional Chinese medicine monomer Inflammation

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Dopaminergic Remodeling During a Critical Developmental Window:Linking Drug Use to Adult Aggression

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Neuroscience Bulletin 2024年第6期40卷 845-848页

作者： Dadao An Lingyan Zheng Zhengyi Xu Yanrong Zheng Zhong Chen key laboratory of Neuropharmacology and translational medicine of Zhejiang Province Zhejiang Chinese Medical UniversityHangzhou310053China

Behaviors can be shaped and modulated by the dopamine system,which can be remodeled in adolescents due to environmental factors,including pharmacologic exposure,stress,and rewarding experiences,leading to various adolescentonset neuropsychiatric disorders[1-3].A deficiency of dopamine transporter(DAT),responsible for reuptaking extracellular DA.

关键词： Window shaped Dopamine

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MIL-100(V) derived porous vanadium oxide/carbon microspheres with oxygen defects and intercalated water molecules as high-performance cathode for aqueous zinc ion battery

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Journal of Energy Chemistry 2024年第3期90卷 578-589,I0013页

作者： Yuexin Liu Jian Huang Xiaoyu Li Jiajia Li Jinhu Yang Kefeng Cai Shanghai key laboratory of Development and Application for Metal-functional Materials Key Laboratory of Advanced Civil Engineering MaterialsMinistry of EducationSchool of Materials Science&EngineeringTongji UniversityShanghai 201804China State key laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghai 201800China Research Center for translational medicine East HospitalTongji University School of MedicineShanghai 200092China

The development of aqueous zinc ion battery cathode materials with high capacity and high magnification is still a ***,porous vanadium oxide/carbon(p-VO_(x)@C,mainly VO_(2) with a small amount of V_(2)O_(3)) core/shell microspheres with oxygen vacancies are facilely fabricated by using a vanadium-based metal-organic framework(MIL-100(V)) as a sacrificial *** unique structure can improve the conductivity of the VO_(x),accelerate electrolyte diffusion,and suppress structural collapse during ***,H_(2)O molecules are introduced into the interlayer of VO_(x) through a highly efficient in-situ electrochemical activation process,facilitating the intercalation and diffusion of zinc *** the activation,an optimal sample exhibits a high specific capacity of 464.3 mA h g^(-1) at0.2 A g^(-1) and 395.2 mA h g^(-1) at 10 A g^(-1),indicating excellent rate ***,the optimal sample maintains a capacity retention of about 89.3% after 2500 cycles at 10 A g^(-1).Density functional theory calculation demonstrates that the presence of oxygen vacancies and intercalated water molecules can significantly reduce the diffusion barrier for zinc *** addition,it is proved that the storage of zinc ions in the cathode is achieved by reversible intercalation/extraction during the charge and discharge process through various ex-situ analysis *** work demonstrates that the p-VO_(x)@C has great potential for applications in aqueous ZIBs after electrochemical activation.

关键词： Metal-organic frameworks Vanadium oxide Carbon Zn-ion batteries Electrochemical activation

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Differences in the effects and action modes of gut commensals against dextran sulfate sodium-induced intestinal inflammation

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Food Science and Human Wellness 2024年第3期13卷 1201-1211页

作者： Dingwu Qu Zhennan Gu Saisai Feng Leilei Yu Fengwei Tian Hao Zhang Wei Chen Qixiao Zhai State key laboratory of Food Science and Technology Jiangnan UniversityWuxi 214122China School of Food Science and Technology Jiangnan UniversityWuxi 214122China National Engineering Research Center for functional Food Jiangnan UniversityWuxi 214122China Wuxi translational medicine Research Center and Jiangsu translational medicine Research Institute Wuxi Branch Wuxi 214122China

Inflammatory bowel disease(IBD)is a complex relapsing inflammatory disease in the gut and is driven by complicated host-gut microbiome *** commensals have shown different functions in IBD prevention and *** gain a mechanistic understanding of how different commensals affect intestinal inflammation,we compared the protective effects of 6 probiotics(belonging to the genera Akkermansia,Bifidobacterium,Clostridium,and Enterococcus)on dextran sulfate sodium(DSS)-induced colitis in mice with or without gut ***-inflammatory properties(ratio of interleukin(IL)-10 and IL-12)of these strains were also evaluated in an in vitro mesenteric lymph nodes(MLN)co-culture *** showed that 4 probiotics(belonging to the species Bifidobacterium breve,Bifidobacterium bifidum,and Enterococcus faecalis)can alleviate colitis in normal *** probiotic strains differed in regulating the intestinal microbiota,cytokines(IL-10,IL-1βand interferon(IFN)-γ),and tight junction function(Zonulin-1 and Occludin).By constrast,Akkermansia muciniphila AH39 and Clostridium butyricum FHuNHHMY49T1 were not ***,*** JSNJJNM2 with high anti-inflammatory potential in the MLN model could relieve colitis symptoms in antibiotic cocktail(Abx)-treated ***,*** FJSWX25M1induced low levels of cytokines in vitro and showed no beneficial ***,we provided insight into the clinical application of probiotics in IBD treatment.

关键词： Gut commensals Dextran sulfate sodium(DSS)colitis Intestinal barrier Immunoregulation

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Satellite glial cells in sensory ganglia play a wider role in chronic pain via multiple mechanisms

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Neural Regeneration Research 2024年第5期19卷 1056-1063页

作者： Xiaoyun Qiu Yuanzhi Yang Xiaoli Da Yi Wang Zhong Chen Cenglin Xu key laboratory of Neuropharmacology and translational medicine of Zhejiang Province School of Pharmaceutical ScienceZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina

Satellite glial cells are unique glial cells that surround the cell body of primary sensory *** increasing body of evidence suggests that in the presence of inflammation and nerve damage,a significant number of satellite glial cells become activated,thus triggering a series of functional *** suggests that satellite glial cells are closely related to the occurrence of chronic *** this review,we first summarize the morphological structure,molecular markers,and physiological functions of satellite glial ***,we clarify the multiple key roles of satellite glial cells in chronic pain,including gap junction hemichannel Cx43,membrane channel Pannexin1,K channel subunit 4.1,ATP,purinergic P2 receptors,and a series of additional factors and their receptors,including tumor necrosis factor,glutamate,endothelin,and ***,we propose that future research should focus on the specific sorting of satellite glial cells,and identify genomic differences between physiological and pathological *** review provides an important perspective for clarifying mechanisms underlying the peripheral regulation of chronic pain and will facilitate the formulation of new treatment plans for chronic pain.

关键词： chronic pain primary sensory neurons satellite glial cells sensory ganglia

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PINK1 is involved in determining the cellular autophagic hierarchy

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Science China(Life Sciences) 2024年第5期67卷 1087-1088页

作者： Zhuchen Zhou Zhong Chen Yanrong Zheng key laboratory of Neuropharmacology and translational medicine of Zhejiang Province School of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhou 311402China

The protein PINK1 plays a crucial role in the regulation of the cellular autophagic ***,a highly conserved biological process,serves as a mechanism for the degradation of intracellular components by *** play a pivotal role in this process by selectively sequestering specific targets,including damaged organelles,protein aggregates,and pathogens.

关键词： PINK1 determining hierarchy

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OIP5 Interacts with NCK2 to Mediate Human Spermatogonial Stem Cell Self-Renewal and Apoptosis through Cell Cyclins and Cycle Progression and Its Abnormality Is Correlated with Male Infertility

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Research 2024年第1期2023卷 455-469页

作者： Yinghong Cui Wei Chen Li Du Zuping He The key laboratory of Model Animals and Stem Cell Biology in Hunan Province The Research Center of Reproduction and Translational Medicine of Hunan ProvinceHunan Normal University School of MedicineChangsha 410013HunanChina

Spermatogonial stem cells(SSCs)have important applications in both reproduction and regenerative ***,specific genes and signaling transduction pathways in mediating fate decisions of human SSCs remain ***,we have demonstrated for the first time that OIP5(Opa interacting protein 5)controlled the self-renewal and apoptosis of human *** sequencing identified that NCK2 was a target for OIP5 in human SSCs,and interestingly,OIP5 could interact with NCK2 as shown by Co-IP(co-immunoprecipitation),IP-MS(mass spectrometry),and GST pulldown ***2 silencing decreased human SSC proliferation and DNA synthesis but enhanced their ***,NCK2 knockdown reversed the influence of OIP5 overexpression on human ***,OIP5 inhibition decreased the numbers of human SSCs at S and G2/M phases,while the levels of numerous cell cycle proteins,including cyclins A2,B1,D1,E1 and H,especially cyclin D1,were remarkably ***,whole-exome sequencing of 777 patients with nonobstructive azoospermia(NOA)revealed 54 singlenucleotide polymorphism mutations of the OIP5 gene(6.95%),while the level of OIP5 protein was obviously lower in testes of NOA patients compared to fertile ***,these results implicate that OIP5 interacts with NCK2 to modulate human SSC self-renewal and apoptosis via cell cyclins and cell cycle progression and that its mutation and/or lower expression is correlated with *** such,this study offers novel insights into molecular mechanisms underlying the fate determinations of human SSCs and the pathogenesis of NOA,and it provides new targets for treating male infertility.

关键词： OIP5 Apoptosis reversed

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