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Suppression of ITPKB degradation by Trim25 confers TMZ resistance in glioblastoma through ROS homeostasis

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1637-1650页

作者： Yuanliang Yan Shangjun Zhou Xi Chen Qiaoli Yi Songshan Feng Zijin Zhao Yuanhong Liu Qiuju Liang Zhijie Xu Zhi Li Lunquan Sun Department of Pharmacy Xiangya HospitalCentral South UniversityChangsha 410008China Department of Neurosurgery Xiangya HospitalCentral South UniversityChangsha 410008China Department of Pathology Xiangya HospitalCentral South UniversityChangsha 410008China xiangya Cancer Center Xiangya HospitalCentral South UniversityChangsha 410008China Key Laboratory of Molecular Radiation Oncology Hunan Province Changsha 410008China institute of Cancer Research National Clinical Research Center for Geriatric Disorders(Xiangya)Xiangya HospitalCentral South UniversityChangsha 410008China

Temozolomide(TMZ)represents a standard-of-care chemotherapeutic agent in glioblastoma(GBM).However,the development of drug resistance constitutes a significant hurdle in the treatment of malignant *** specific innovative approaches,such as immunotherapy,have shown favorable clinical outcomes,the inherent invasiveness of most gliomas continues to make them challenging to ***,there is an urgent need to identify effective therapeutic targets for gliomas to overcome chemoresistance and facilitate drug *** investigation used mass spectrometry to examine the proteomic profiles of six pairs of GBM patients who underwent standard-of-care treatment and surgery for both primary and recurrent tumors.A total of 648 proteins exhibiting significant differential expression were *** Set Enrichment Analysis(GSEA)unveiled notable alterations in pathways related to METABOLISM_OF_LIPIDS and BIOLOGICAL_OXIDATIONS between the primary and recurrent *** through glioma tissue arrays and the xiangya cohort confirmed substantial upregulation of inositol 1,4,5-triphosphate(IP3)kinase B(ITPKB)in the recurrence group,correlating with poor survival in glioma *** TMZ-resistant cells,the depletion of ITPKB led to an increase in reactive oxygen species(ROS)related to NADPH oxidase(NOX)activity and restored cell sensitivity to ***,the decreased phosphorylation of the E3 ligase Trim25 at the S100 position in recurrent GBM samples accounted for the weakened ITPKB ***,in turn,elevated ITPKB stability and impaired ROS ***,ITPKB depletion or the ITPKB inhibitor GNF362 effectively overcome TMZ chemoresistance in a glioma xenograft mouse *** findings reveal a novel mechanism underlying TMZ resistance and propose ITPKB as a promising therapeutic target forTMZ-resistant GBM.

关键词： TMZ homeostasis impaired

A novel mutation of glycogen synthase kinase-3β leads to a reduced level of GSK3βprotein in a patient with dilated cardiomyopathy

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Genes & Diseases 2024年第1期11卷 84-86页

作者： Ke Gong Zhiping Tan Haidan Liu Xiaobo Liao Xinmin Zhou Bangliang Yin Shi Zeng Yao Yao Yifeng Yang Li Xie Department of Cardiovascular Surgery The Second Xiangya Hospital of Central South UniversityCentral South UniversityChangshaHunan410011China Department of Ultrasound The Second Xiangya Hospital of Central South UniversityCentral South UniversityChangshaHunan 410011China Department of Blood Transfusion The Second Xiangya Hospital of Central South UniversityCentral South UniversityChangshaHunan 410011China

Dilated cardiomyopathy(DCM)is a frequently inherited heart condition.A familial transmission rate of 20%-35%has been documented,and most of these cases are autosomal *** condition has a high rate of morbidity and mort... 详细信息

关键词： GSK3β cardiomyopathy mortality

Glymphatic system:a gateway for neuroinflammation

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Neural Regeneration Research 2024年第12期19卷 2661-2672页

作者： Kailu Zou Qingwei Deng Hong Zhang Changsheng Huang Department of Anesthesiology Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina xiangya School of Medicine Central South UniversityChangshaHunan ProvinceChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

The glymphatic system is a relatively recently identified fluid exchange and transpo rt system in the *** evidence indicates thatglymphatic function is impaired not only in central nervous system disorders but also in systemic *** diseases can trigger the inflammatory responses in the central nervous system,occasionally leading to sustained inflammation and functional disturbance of the central nervous *** review summarizes the current knowledge on the association between glymphatic dysfunction and central nervous system *** addition,we discuss the hypothesis that disease conditions initially associated with peripheral inflammation ove rwhelm the performance of the glymphatic system,thereby triggering central nervous system dysfun ction,chronic neuroinflammation,and *** research investigating the role of the glymphatic system in neuroinflammation may offer innovative therapeutic approaches for central nervous system disorders.

关键词： aquaporin-4 central nervous system disease cerebrospinal fluid chronic neuroinflammation glymphatic dysfunction neurodegeneration peripheral nerve injury perivascular space systemic disease vicious cycle

Apatinib and gamabufotalin co-loaded lipid/Prussian blue nanoparticles for synergistic therapy to gastric cancer with metastasis

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Journal of Pharmaceutical Analysis 2024年第5期14卷 707-721页

作者： Binlong Chen Yanzhong Zhao Zichang Lin Jiahao Liang Jialong Fan Yanyan Huang Leye He Bin Liu Health Management Center The Third Xiangya HospitalCentral South UniversityChangsha410013China Department of Urology The Third Xiangya HospitalCentral South UniversityChangsha410013China Department of Laboratory Medicine The Third Xiangya HospitalCentral South UniversityChangsha410013China College of Biology Hunan UniversityChangsha410082China

Due to the non-targeted release and low solubility of anti-gastric cancer agent,apatinib(Apa),a first-line drug with long-term usage in a high dosage often induces multi-drug resistance and causes serious side *** order to avoid these drawbacks,lipid-film-coated Prussian blue nanoparticles(PB NPs)with hyaluronan(HA)modification was used for Apa loading to improve its solubility and targeting ***,anti-tumor compound of gamabufotalin(CS-6)was selected as a partner of Apawith reducing dosage for combinational gastric ***,HA-Apa-Lip@PB-CS-6 NPs were constructed to synchronously transport the two drugs into tumor *** vitro assay indicated that HA-Apa-Lip@PB-CS-6 NPs can synergistically inhibit proliferation and invasion/metastasis of BGC-823 cells via downregulating vascular endothelial growth factor receptor(VEGFR)and matrix metalloproteinase-9(MMP-9).In vivo assay demonstrated strongest anti-tumor growth and liver metastasis of HA-Apa-Lip@PB-CS-6 NPs administration in BGC-823 cells-bearing mice compared with other groups due to the excellent penetration in tumor tissues and outstanding synergistic *** summary,we have successfully developed a new nanocomplexes for synchronous Apa/CS-6 delivery and synergistic gastric cancer(GC)therapy.

关键词： Apatinib Gamabufotalin Lipid/Prussian blue nanoparticles Gastric cancer

Identification of a novel MYO1D variant associated with laterality defects,congenital heart diseases,and sperm defects in humans

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Frontiers of Medicine 2024年第3期18卷 558-564页

作者： Zhuangzhuang Yuan Xin Zhu Xiaohui Xie Chenyu Wang Heng Gu Junlin Yang Liangliang Fan Rong Xiang Yifeng Yang Zhiping Tan Department of Cardiovascular Surgery The Second Xiangya Hospital of Central South UniversityChangsha410011China Clinical Center for Gene Diagnosis and Therapy The Second Xiangya Hospital of Central South UniversityChangsha410011China Department of Cell Biology School of Life SciencesCentral South UniversityChangsha410013China Department of Gynecology and Obstetrics Xiangya Hospital of Central South UniversityChangsha410008China

The establishment of left–right asymmetry is a fundamental process in animal *** with this process leads to a range of disorders collectively known as laterality defects,which manifest as abnormal arrangements of visceral *** patients with laterality defects,congenital heart diseases(CHD)are *** multiple model organisms,extant research has established that myosin-Id(MYO1D)deficiency causes laterality *** study investigated over a hundred cases and identified a novel biallelic variant of MYO1D(NM_015194:c.1531G>A;p.D511N)in a consanguineous family with complex CHD and laterality *** examination of the proband revealed asthenoteratozoospermia and shortened ***,the effects of the D511N variant and another known MYO1D variant(NM_015194:c.2293C>T;p.P765S)were *** assessment showed that both enhance the interaction withβ-actin and ***,this study revealed the genetic heterogeneity of this rare disease and found that MYO1D variants are correlated with laterality defects and CHD in ***,this research established a connection between sperm defects and MYO1D *** offers guidance for exploring infertility and reproductive health *** findings provide a critical basis for advancing personalized medicine and genetic counseling.

关键词： MYO1D laterality defect congenital heart disease sperm defect β-actin SPAG6

Health outcomes of electronic cigarettes

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中华医学杂志(英文版) 2024年第16期137卷 1903-1911页

作者： Li Xinmeng Yuan Lingzhi Wang Fen Department of Gastroenterology The Third Xiangya Hospital Central South University Changsha Hunan China Hunan Key Laboratory of Non-resolving Inflammation and Cancer The Third Xiangya Hospital Central South University Changsha Hunan China

The usage of electronic cigarettes (e-cigarettes) sparked an outbreak of unidentified vaping-related lung disease in the US during late 2019. With e-cigarettes becoming more and more popular, smokers have more options other than conventional cigarettes. Under these circumstances, a comprehensive evaluation of the general safety of new tobacco and tobacco-related products, represented by e-cigarettes, to human health is necessary. In this review, we summarize the current research on potential negative impacts of e-cigarette exposure on human health. In particular, studies detailing the relationship between e-cigarettes and the digestive system are summarized, with mechanisms mainly including hepatic metabolic dysfunction, impaired gut barrier, and worsened outcomes of inflammatory bowel disease (IBD). Although believed to be safer than traditional cigarettes, e-cigarettes exert adverse effects on systemic health and induce the development of multiple diseases including asthma, cardiovascular disease, and IBD. Moreover, nicotine-containing e-cigarettes have a negative impact on the childhood development and increase the risk of arterial stiffness compared to the non-nicotine e-cigarettes. However, non-nicotine e-cigarette components have detrimental effects including promoting liver damage and metabolic disorders.

关键词： Electronic cigarettes Electronic nicotine delivery system Smoking cessation Health promotion Tobacco harm reduction Smoker

Kdm6a-CNN1 axis orchestrates epigenetic control of traumainduced spinal cord microvascular endothelial cell senescence to balance neuroinflammation for improved neurological repair

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Bone Research 2024年第2期12卷 314-333页

作者： Chengjun Li Tian Qin Jinyun Zhao Yuxin Jin Yiming Qin Rundong He Tianding Wu Chunyue Duan Liyuan Jiang Feifei Yuan Hongbin Lu Yong Cao Jianzhong Hu Department of Sports Medicine Xiangya HospitalCentral South UniversityXiangya Road 87Changsha 410008China Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceXiangya Road 87Changsha 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityXiangya Road 87Changsha 410008China Department of Spine Surgery and Orthopaedics Xiangya HospitalCentral South UniversityXiangya Road 87Changsha 410008China

Cellular senescence assumes pivotal roles in various diseases through the secretion of proinflammatory *** extensive investigations into vascular senescence associated with aging and degenerative diseases,the molecular mechanisms governing microvascular endothelial cell senescence induced by traumatic stress,particularly its involvement in senescence-induced inflammation,remain insufficiently *** this study,we present a comprehensive demonstration and characterization of microvascular endothelial cell senescence induced by spinal cord injury(SCI).Lysine demethylase 6A(Kdm6a),commonly known as UTX,emerges as a crucial regulator of cell senescence in injured spinal cord microvascular endothelial cells(SCMECs).Upregulation of UTX induces senescence in SCMECs,leading to an amplified release of proinflammatory factors,specifically the senescenceassociated secretory phenotype(SASP)components,thereby modulating the inflammatory ***,the deletion of UTX in endothelial cells shields SCMECs against senescence,mitigates the release of proinflammatory SASP factors,and promotes neurological functional recovery after *** forms an epigenetic regulatory axis by binding to calponin 1(CNN1),orchestrating trauma-induced SCMECs senescence and SASP secretion,thereby influencing neuroinflammation and neurological functional ***,local delivery of a senolytic drug reduces senescent SCMECs and suppresses proinflammatory SASP secretion,reinstating a local regenerative microenvironment and enhancing functional repair after *** conclusion,targeting the UTX-CNN1 epigenetic axis to prevent trauma-induced SCMECs senescence holds the potential to inhibit SASP secretion,alleviate neuroinflammation,and provide a novel treatment strategy for SCI repair.

关键词： inflammation epigenetic neurological

First-line immunotherapy for advanced non-small cell lung cancer:current progress and future prospects

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Cancer Biology & Medicine 2024年第2期21卷 117-124页

作者： Jingyi Wang Lin Wu The Second Department of Thoracic Oncology Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China xiangya Lung Cancer Center Xiangya HospitalCentral South UniversityChangsha 410008China

Global Cancer Statistics 2022 reported the prevalence and high mortality rate of lung ***,non-small cell lung cancer(NSCLC)accounts for the majority of the histologic *** therapy for lung cancer has progressed rapidly and immune checkpoint inhibitors(ICIs)have become a leading research ***,ICI therapy has been shown to improve the prognosis of lung cancer patients.

关键词： lung cancer mortality

Prognostic and clinical value of circPRKCI expression in diverse human cancers

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Chinese Medical Journal 2024年第2期137卷 152-161页

作者： Zhongyue Liu Xiaolei Ren Zhimin Yang Lin Mei Wenyi Li Chao Tu Zhihong Li Department of Orthopedics The Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China Hunan Key Laboratory of Tumor Models and Individualized Medicine The Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China

Background:Highly expressed in various human cancers,circular RNA Protein Kinase C Iota(circPRKCI)has been reported to play an important role in cancer development and ***,we sought to reveal the prognostic and clinical value of circPRKCI expression in diverse human ***:We searched the Pubmed,Web of Science,and the Cochrane Library databases from inception until May 16,*** relationship between circPRKCI expression and cancer patients’survival,including overall survival(OS)and disease-free survival(DFS),was assessed by pooled hazard ratios(HR)with corresponding 95%confidence interval(CI).The correlation between circPRKCI expression and clinical outcomes was evaluated using odds ratios(OR)with corresponding 95%*** data were analyzed by STATA software(version 12.0)or Review Manager(RevMan 5.3).Results:A total of 15 studies with 1109 patients were incorporated into our *** results demonstrated that high circPRKCI expression was significantly related to poor OS(HR=1.96,95%CI:1.61,2.39,P<0.001)when compared with low circPRKCI expression in diverse human ***,elevated circPRKCI expression was not associated with DFS(HR=1.34,95%CI:0.93,1.95,P=0.121).Furthermore,the patient with a higher circPRKCI expression was prone to have a larger tumor size,advanced clinical stage,and lymph node metastasis,but it was not significantly correlated with age,gender,and distant ***:Elevated circPRKCI expression was correlated with worse OS and unfavorable clinical features,suggesting a novel prognostic and predictive role of circPRKCI in diverse human cancers.

关键词： CircPRKCI Cancer Prognosis Overall survival Meta-analysis Circular RNA Protein Kinase C Iota