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Cav3.2 channel regulates cerebral ischemia/reperfusion injury:a promising target for intervention

Neural Regeneration Research 2024年第11期19卷 2480-2487页

作者： Feibiao Dai Chengyun Hu Xue Li Zhetao Zhang Hongtao Wang Wanjun Zhou Jiawu Wang Qingtian Geng Yongfei Dong Chaoliang Tang Graduate School Wannan Medical CollegeWuhuAnhui ProvinceChina Department of Anesthesiology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Core Facility Center for Medical sciences The First Affiliated Hospital of USTC(Anhui Provincial Hospital)HefeiAnhui ProvinceChina Department of Pharmacy The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Department of Neurosurgery The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina

Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion *** calcium channels are involved in cerebral ischemia/reperfusion ***3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain ***,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains ***,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal *** results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal *** further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion ***3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion ***,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal *** the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion *** findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 *** from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.

关键词： calcineurin Cav3.2 channel cerebral ischemia/reperfusion hippocampus hypoxia/reoxygenation inflammatory response nuclear factor of activated T cells 3 oxidative stress primary hippocampal neurons stroke

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Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress

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Journal of Integrative Medicine 2024年第4期22卷 493-502页

作者： Qian-zhuo Liu Hui Han Xin-ru Fang Lu-yao Wang Dan Zhao Miao-zhu Yin Nian Zhang Peng-yu Jiang Zhi-hui Ji Li-min Wu Department of Neurology the First Affiliated Hospital of Anhui University of Chinese MedicineHefei 230031Anhui ProvinceChina Center for Reproduction and Genetics the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230031Anhui ProvinceChina

Objective:Hepatolenticular degeneration (HLD) is an autosomal recessive disorder that manifests as multiorgan damage due to impaired copper (Cu) metabolism. Female patients with HLD often experience reproductive impairments. This study investigated the protective effect of berberine against ovarian damage in toxic-milk (TX) mice, a murine model for ***:Mice were categorized into control group, HLD TX group (HLD group), penicillamine (Cu chelator)-treated TX group and berberine-treated TX group. Body weight, ovary weight and the number of ovulated eggs were recorded. Follicular morphology and cellular ultrastructure were examined. Total iron, ferrous iron (Fe2+) and trivalent iron (Fe3+) levels, as well as malondialdehyde (MDA), glutathione(GSH) and oxidized glutathione (GSSG), were measured in the ovaries. Western blot analysis was used to analyze the expression of proteins related to ferroptosis and endoplasmic reticulum (ER) ***:Ovarian tissue damage was evident in the HLD group, with a significant increase in ferroptosis and ER stress compared to the control group. This damage was inhibited by treatment with penicillamine,a Cu chelator. Compared with the HLD group, berberine increased the number of ovulations, and improved ovarian morphology and ultrastructure. Further, we found that berberine reduced total iron,Fe2+, MDA and GSSG levels, elevated GSH levels, decreased the expression of the ferroptosis marker protein prostaglandin-endoperoxide synthase 2 (PTGS2), and increased glutathione peroxidase 4 (GPX4)expression. Furthermore, berberine inhibited the expression of ER stress-associated proteins mediated by the protein kinase RNA-like ER kinase (PERK) ***:Ferroptosis and ER stress are involved in Cu-induced ovarian damage in TX mice. Berberine ameliorates ovarian damage in HLD TX mice by inhibiting ferroptosis and ER stress.

关键词： Berberine Hepatolenticular degeneration Copper deposition Ferroptosis Endoplasmic reticulum stress

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In vivo imaging reveals a synchronized correlation among neurotransmitter dynamics during propofol and sevoflurane anesthesia

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Zoological Research 2024年第3期45卷 679-690页

作者： Gao-Lin Qiu Li-Jun Peng Peng Wang Zhi-Lai Yang Ji-Qian Zhang Hu Liu Xiao-Na Zhu Jin Rao Xue-Sheng Liu Department of Anesthesiology First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China School of Life science and technology ShanghaiTech UniversityShanghai 201210China

General anesthesia is widely applied in clinical ***,the precise mechanism of loss of consciousness induced by general anesthetics remains ***,we measured the dynamics of five neurotransmitters,includingγ-aminobutyric acid,glutamate,norepinephrine,acetylcholine,and dopamine,in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter *** revealed that the concentrations of γ-aminobutyric acid,glutamate,norepinephrine,and acetylcholine increased in the cortex during propofol-induced loss of *** levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol ***,the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of ***,the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic *** findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.

关键词： General anesthesia Loss of consciousness In vivo neurotransmitter imaging Medial prefrontal cortex Primary visual cortex

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Postoperative epidural hematoma as a rare complication after intracranial tumor resection: a case series report and causes analysis

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中华神经外科杂志(英文) 2024年第2期10卷 83-91页

作者： Zeng Minghui Li Zhijin Xia Chunsheng Cheng Xufeng Wang Yehan Wang Fei Department of Neurosurgery The First Affiliated Hospital of USTC (Anhui Provincial Hospital) Division of Life Science and Medicine University of Science and Technology of China Hefei Anhui China

Background To review the treatment and the causes of postoperative epidural hematoma (PEDH) after intracranial tumor *** A retrospective case study was conducted to examine a series of patients who developed PEDH as a complication following intracranial tumor resection between January 2016 and June 2021. The study collected data from hospital charts, including clinical status at admission, imaging results, histopathologic findings, surgical management, complications, and outcomes. Causes of PEDH were evaluated through a review of operative notes and discussions with the surgical *** Twenty-five patients (10 males, 15 females; median age 42 years, range 11-61 years; median medical history 27 months, range 1-96 months) were enrolled in the study. Regarding tumor location, 16 cases exhibited supratentorial brain tumors, 4 cases had infratentorial brain tumors, 2 cases of tumors occurred in the petroclival region, 2 cases in the peritorcular region, and 1 case in the pineal region. Four of these cases were complicated with supratentorial hydrocephalus. The 25 cases in this study were classified into four types based on location. Type 1 refers to EDHs that occur at the adjacent site of the operative field without involvement of the surgical area. Type 2 includes hematomas that occur at the adjacent site of the surgical area and the surgical area. Type 3 includes EDHs that occur in distant areas, and type 4 involves EDHs in the surgical field. The numbers of cases of types 1, 2, 3, and 4 PEDHs were 16, 2, 3, and 4 cases, respectively. Most PEDHs were associated with reduced ICP after craniotomy due to intracranial tumor resection and substantial loss of CSF. All patients achieved satisfactory outcomes after hematoma *** The decrease in ICP resulting from intracranial tumor resection and CSF loss might lead to PEDHs. By employing optimized surgical techniques and meticulous patient management to prevent rapid decreases in ICP and dur

关键词： Epidural hematoma Postoperative complication Craniotomy Brain tumor

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Computed tomography-based radiomics to predict early recurrence of hepatocellular carcinoma post-hepatectomy in patients background on cirrhosis

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World Journal of Gastroenterology 2024年第15期30卷 2128-2142页

作者： Gui-Xiang Qian Zi-Ling Xu Yong-Hai Li Jian-Lin Lu Xiang-Yi Bu Ming-Tong Wei Wei-Dong Jia Department of Hepatic Surgery Anhui Provincial HospitalThe First Affiliated Hospital of USTCDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina Department of Hepatic Surgery Anhui Provincial Hospital Affiliated to Anhui Medical UniversityAnhui Medical UniversityHefei 230001Anhui ProvinceChina Department of Anorectal Surgery the First People’s Hospital of HefeiHefei 230001Anhui ProvinceChina

BACKGROUND The prognosis for hepatocellular carcinoma(HCC)in the presence of cirrhosis is unfavourable,primarily attributable to the high incidence of *** To develop a machine learning model for predicting early recurrence(ER)of posthepatectomy HCC in patients with cirrhosis and to stratify patients’overall survival(OS)based on the predicted risk of *** In this retrospective study,214 HCC patients with cirrhosis who underwent curative hepatectomy were *** feature selection was conducted using the least absolute shrinkage and selection operator and recursive feature elimination ***-radiologic features were selected through univariate and multivariate logistic regression *** machine learning methods were used for model comparison,aiming to identify the optimal *** model’s performance was evaluated using the receiver operating characteristic curve[area under the curve(AUC)],calibration,and decision curve ***,the Kaplan-Meier(K-M)curve was used to evaluate the stratification effect of the model on patient *** Within this study,the most effective predictive performance for ER of post-hepatectomy HCC in the background of cirrhosis was demonstrated by a model that integrated radiomics features and clinical-radiologic *** the training cohort,this model attained an AUC of 0.844,while in the validation cohort,it achieved a value of *** K-M curves illustrated that the combined model not only facilitated risk stratification but also exhibited significant discriminatory ability concerning patients’*** The combined model,integrating both radiomics and clinical-radiologic characteristics,exhibited excellent performance in HCC with *** K-M curves assessing OS revealed statistically significant differences.

关键词： Machine learning Radiomics Hepatocellular carcinoma Cirrhosis Early recurrence Overall survival Computed tomography Prognosis Risk factor Delta-radiomics

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Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease

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Chinese Medical Journal 2024年第10期137卷 1207-1217页

作者： Tianzhong Pan Peng Ding Aijie Huang Baolin Tang Kaidi Song Guangyu Sun Yue Wu Shiying Yang Xingchi Chen Dongyao Wang Xiaoyu Zhu Department of Hematology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China anhui Provincial Key Laboratory of Blood Research and Applications HefeiAnhui230001China Blood and Cell Therapy Institute Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China Division of Life sciences and Medicine University of Science and Technology of ChinaHefeiAnhui 230001China The first affiliated hospital of USTC Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China

Background:With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation(UCBT),the correlation between immune reconstitution(IR)after UCBT and graft-versus-host disease(GVHD)has been reported successively,but reports on double-negative T(DNT)cell reconstitution and its association with acute GVHD(aGVHD)after UCBT are ***:A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology,the first affiliated hospital of USTC,between August 2018 and June *** differences were compared between the patients with and without ***:The absolute number of DNT cells in the healthy Chinese population was 109(70-157)/μL,accounting for 5.82(3.98-8.19)%of *** cells showed delayed recovery and could not reach their normal levels even one year after ***,the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year(F=4.684,P=0.039 and F=5.583,P=0.026,respectively).In addition,the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased,and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD(HR=0.46,95%confidence interval[CI]:0.23-0.93;P=0.031).Conclusions:Compared to the number of DNT cells in Chinese healthy people,the reconstitution of DNT cells in adults with hematological malignancies after UCBT was *** addition,the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

关键词： Umbilical cord blood transplantation Graft-versus-host disease Immune reconstitution Double negative T Hematological Malignancies Treg cell Breg cell

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Application of non-mydriatic fundus photography-assisted telemedicine in diabetic retinopathy screening

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World Journal of Diabetes 2024年第2期15卷 251-259页

作者： Wan Zhou Xiao-Jing Yuan Jie Li Wei Wang Hao-Qiang Zhang Yuan-Yuan Hu Shan-Dong Ye Department of Endocrinology The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina Department of Endocrinology Anhui Provincial HospitalAffiliated to Anhui Medical UniversityHefei 230001Anhui ProvinceChina

BACKGROUND Early screening and accurate staging of diabetic retinopathy(DR)can reduce blindness risk in type 2 diabetes ***’s complex pathogenesis involves many factors,making ophthalmologist screening alone insufficient for prevention and ***,endocrinologists are the first to see diabetic patients and thus should screen for retinopathy for early *** To explore the efficacy of non-mydriatic fundus photography(NMFP)-enhanced telemedicine in assessing DR and its various *** This retrospective study incorporated findings from an analysis of 93 diabetic patients,examining both NMFP-assisted telemedicine and fundus fluorescein angiography(FFA).It focused on assessing the concordance in DR detection between these two ***,receiver operating characteristic(ROC)curves were generated to determine the optimal sensitivity and specificity of NMFP-assisted telemedicine,using FFA outcomes as the standard *** In the context of DR diagnosis and staging,the kappa coefficients for NMFPassisted telemedicine and FFA were recorded at 0.775 and 0.689 respectively,indicating substantial intermethod ***,the NMFP-assisted telemedicine’s predictive accuracy for positive FFA outcomes,as denoted by the area under the ROC curve,was remarkably high at 0.955,within a confidence interval of 0.914 to 0.995 and a statistically significant P-value of less than *** predictive model exhibited a specificity of 100%,a sensitivity of 90.9%,and a Youden index of *** NMFP-assisted telemedicine represents a pragmatic,objective,and precise modality for fundus examination,particularly applicable in the context of endocrinology inpatient care and primary healthcare settings for diabetic *** implementation in these scenarios is of paramount significance,enhancing the clinical accuracy in the diagnosis and therapeutic management of *** methodology not only streamlines patient evaluation

关键词： Diabetes Diabetic retinopathy Non-mydriatic fundus photography-assisted telemedicine Fundus fluorescein angiography

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Metal natural product complex Ru-procyanidins with quadruple enzymatic activity combat infections from drug-resistant bacteria

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2298-2316页

作者： Jie Shan Xu Jin Cong Zhang Muchen Huang Jianghao Xing Qingrong Li Yuyu Cui Qiang Niu Xu Lin Chen Xianwen Wang Department of Burns the First Affiliated Hospital of Anhui Medical UniversityHefei 230022China School of Biomedical Engineering Research and Engineering Center of Biomedical MaterialsAnhui Provincial Institute of Translational MedicineAnhui Medical UniversityHefei 230032China Division of Gastroenterology the First Affiliated Hospital of USTCDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230026China The Second Clinical Medical College Anhui Medical UniversityHefei 230022China Department of Oncology the First Affiliated Hospital of Anhui Medical UniversityHefei 230022China College and hospital of Stomatology Anhui Medical UniversityKey Lab.of Oral Diseases Research of Anhui ProvinceHefei 230032China

Bacterial infection hampers wound repair by impeding the healing ***,inflammation at the wound site triggers the production of reactive oxygen species(ROS),causing oxidative stress and damage to proteins and *** can lead to chronic wounds,posing severe ***,eliminating bacterial infection and reducing ROS levels are crucial for effective wound ***,possessing enzyme-like catalytic activity,can convert endogenous substances into highly toxic substances,such as ROS,to combat bacteria and biofilms without inducing drug ***,the current nanozyme model with single enzyme activity falls short of meeting the complex requirements of antimicrobial ***,developing nanozymes with multiple enzymatic activities is ***,we engineered a novel metalloenzyme called Ru-procyanidin nanoparticles(Ru-PC NPs)with diverse enzymatic activities to aid wound healing and combat bacterial *** acidic conditions,due to their glutathione(GSH)depletion and peroxidase(POD)-like activity,Ru-PC NPs combined with H2O2 exhibit excellent antibacterial ***,in a neutral environment,the Ru-PC NPs,with catalase(CAT)activity,decompose H2O2 to O2,alleviating hypoxia and ensuring a sufficient oxygen ***,Ru-PC NPs possess exceptional antioxidant capacity through their superior superoxide dismutase(SOD)enzyme activity,effectively scavenging excess ROS and reactive nitrogen species(RNS)in a neutral *** maintains the balance of the antioxidant system and prevents ***-PC NPs also promote the polarization of macrophages from M1 to M2,facilitating wound *** importantly,Ru-PC NPs show good biosafety with negligible *** vivo wound infection models have confirmed the efficacy of Ru-PC NPs in inhibiting bacterial infection and promoting wound *** focus of this work highlights the quadruple enzymatic activity of Ru-PC NPs and its potential to reduce inf

关键词： Nanozymes Quadruple enzymatic activity Antibacterial therapy Wound therapy RNA-seqAnti-inflammatory Reactive oxygen species Reactive nitrogen species

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Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 331-342页

作者： Hua-Chuan Song Hang-Cheng Zhou Ping Gu Bing Bao Quan Sun Tian-Ming Mei Wei Cui Kang Yao Huan-Zhang Yao Shen-Yu Zhang Yong-Shuai Wang Rui-Peng Song Ji-Zhou Wang Department of General Surgery Provincial Hospital Affiliated to Anhui Medical UniversityHefei 230001Anhui ProvinceChina Department of Hepatobiliary Surgery The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina Department of Pathology The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina Department of Gastrointestinal Surgery Tongcheng People’s HospitalTongcheng 231400Anhui ProvinceChina Department of Gastrointestinal Surgery Suzhou Hospital Affiliated to Anhui Medical UniversitySuzhou 234000Anhui ProvinceChina Department of General Surgery Xuancheng People’s HospitalXuancheng 242000Anhui ProvinceChina

BACKGROUND Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality,with the liver being the primary organ of *** chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases(CRLMs).Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of ***,the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative *** mass index(BMI)is one of the factors affecting the tumori-genesis and progression of colorectal cancer as well as prognosis after various antitumour *** studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight,particularly when receiving first-line chemotherapy regimens in combination with *** To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for *** A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July *** and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological *** Kaplan-Meier method with log rank test was used to compare progression-free survival(PFS)between patients with high and low ***<24.0 kg/m^(2) was defined as low BMI,and tumour regression grade 1-2 was defined as complete tumour *** Low BMI was observed in 74(58.7%)patients and complete tumour response was found in 27(21.4%)*** rate of complete tumour response was significantly higher in patients with low BMI(29.7%vs 9.6%,P=0.007).Multivariate analysis revealed that low BMI[odds ratio(OR)=4.56,95%confidence interval(CI):1

关键词： Colorectal liver metastases Body mass index Tumour regression grade Preoperative chemotherapy Hepatectomy

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Blockade of the deubiquitinating enzyme USP48 degrades oncogenic HMGA2 and inhibits colorectal cancer invasion and metastasis

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1624-1643页

作者： Can Cheng Hanhui Yao Heng Li Jingwen Liu Zhengyi Liu Yang Wu Liang Zhu Hejie Hu Zhengdong Fang Liang Wu Department of General Surgery the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China anhui Province Key Laboratory of Hepatopancreatobiliary Surgery the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Department of Comprehensive Surgery Anhui Provincial Cancer HospitalWest District of the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China anhui Provincial hospital Health Management Center the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Department of Breast Surgery Henan Provincial People's HospitalPeople's Hospital of Zhengzhou UniversityPeople's Hospital of Henan UniversityZhengzhou 450003China

HMGA2,a pivotal transcription factor,functions as a versatile regulator implicated in the progression of diverse aggressive *** this study,mass spectrometry was employed to identify ubiquitin-specific proteases that potentially interact with HMGA2,and USP48 was identified as a deubiquitinating enzyme of *** enforced expression of USP48 significantly increased HMGA2 protein levels by inhibiting its degradation,while the deprivation of USP48 promoted HMGA2 degradation,thereby suppressing tumor invasion and *** discovered that USP48 undergoes SUMOylation at lysine 258,which enhances its binding affinity to *** subsequent phenotypic screening of small molecules,we identified DUB-IN-2 as a remarkably potent pharmacological inhibitor of ***,the small-molecule inhibitor targeting USP48 induces destabilization of ***,upregulation of USP48 or HMGA2 in cancerous tissues is indicative of poor prognosis for patients with colorectal cancer(CRC).Collectively,our study not only elucidates the regulatory mechanism of DUBs involved in HMGA2 stability and validates USP48 as a potential therapeutic target for CRC,but also identifies DUB-IN-2 as a potent inhibitor of USP48 and a promising candidate for CRC treatment.

关键词： Colorectal cancer Invasion and metastasis Post-translational modification Ubiquitination SUMOylation USP48 HMGA2 Specific inhibitors

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