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NAT10-mediated ac 4 C-modified ANKZF1 promotes tumor progression and lymphangiogenesis in clear-cell renal cell carcinoma by attenuating YWHAE-driven cytoplasmic retention of YAP1

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Cancer Communications 2024年第3期44卷 361-383页

作者： Daojia Miao Jian Shi Qingyang Lv Diaoyi Tan Chuanyi Zhao Zhiyong Xiong Xiaoping Zhang department of urology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Institute of urology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China

Background:Lymphatic metastasis is one of the most common metastatic routes and indicates a poor prognosis in clear-cell renal cell carcinoma(ccRCC).N-acetyltransferase 10(NAT10)is known to catalyze N4-acetylcytidine(ac4C)modification of mRNA and participate in many cellular ***,its role in the lymphangiogenic process of ccRCC has not been *** study aimed to elucidate the role of NAT10 in ccRCC lymphangiogenesis,providing valuable insights into potential therapeutic targets for ***:ac4C modification and NAT10 expression levels in ccRCC were assessed using public databases and clinical *** investigations involved manipulating NAT10 expression in cellular and mouse models to study its role in *** insights were gained through a combination of RNA sequencing,mass spectrometry,co-immunoprecipitation,RNA immuno-precipitation,immunofluorescence,and site-specific mutation ***:We found that ac4C modification and NAT10 expression levels increased in ***10 promoted tumor progression and lymphangiogene-sis of ccRCC by enhancing the nuclear import of Yes1-associated transcriptional regulator(YAP1).Subsequently,we identified ankyrin repeat and zinc fin-ger peptidyl tRNA hydrolase 1(ANKZF1)as the functional target of NAT10,and its upregulation in ccRCC was caused by NAT10-mediated ac4C *** analyses demonstrated that ANKZF1 interacted with tyro-sine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon(YWHAE)to competitively inhibit cytoplasmic retention of YAP1,leading to transcriptional activation of pro-lymphangiogenic ***:These results suggested a pro-cancer role of NAT10-mediated acetylation in ccRCC and identified the NAT10/ANKZF1/YAP1 axis as an under-reported pathway involving tumor progression and lymphangiogenesis in ccRCC.

关键词： clear-cell renal cell carcinoma N4-acetylcytidine N-acetyltransferase 10 YAP1 nuclear import

TRAIL and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma Cells via Targeting Wnt/β-catenin Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 322-329页

作者： QIN Jing-jing NIU Meng-da CHA Zhe GENG Qing-hua LI Yu-lin REN Chun-guang David P.Molloy YU Hua-rong Research Center of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Laboratory of Developmental Biology Department of Cell Biology and GeneticsSchool of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China department of Biochemistry and Molecular Biology School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China

Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblastoma *** Cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16µmol/L)and TRAIL(0-500 ng/mL)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIL(TRAIL 100 ng/mL),Cel(celastrol 0.5µmol/L)and TCCT(TRAIL 100 ng/mL+celastrol 0.5µmol/L).Cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,*** reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona occludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(LiCl,20 mol/L)and the mechanism for action of TCCT was *** Celastrol and TRAIL synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(P<0.01).TCCT up-regulated the expression of GSK-3β and down-regulated the expression of β-catenin and its associated proteins(P<0.05 or P<0.01),including c-Myc,Cyclin-D1,and matrix metalloproteinase(MMP)-*** addition,LiCl,an activator of the Wnt signaling pathway,restored the inhibitory effects of TCCT on the expression of β-catenin and its downstream genes,as well as the migration and invasion of glioblastoma cells(P<0.05 or P<0.01).Conclusions Celastrol and TRAIL can synergistically suppress glioblastoma cell migration,invasion,and EMT,potentially through inhibition of Wnt/β-catenin *** underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.

关键词： celastrol Chinese medicine tumor necrosis factor-related apoptosis-induced ligand glioblastoma β-catenin Tripterygium wilfordii

Curcumin Interferes with TGF-β1-Induced Fibrosis in NRK-49F Cells by Reversing ADAMTS18 Gene Methylation

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Chinese Journal of Integrative Medicine 2024年第7期30卷 600-607页

作者： XU Ben ZHANG Jia-en YE Lin YUAN Chang-wei department of urology Peking University First Hospital and Institute of UrologyPeking UniversityNational Urological Cancer CenterBeijing100034China

Objective To explore the molecular mechanism by which curcumin affects renal interstitial fibrosis(RIF)progression by regulating ADAM metallopeptidase with thrombospondin type 1 motif 18(ADAMTS18)*** NRK-49F cells RIF model were induced with transforming growth factorβ1(TGF-β1).Effects of different concentrations of curcumin(0,10,20,and 30μmol/L)on cell proliferation,cell cycle,cell apoptosis as well as cyclin D1 expression were analyzed by cell counting kit-8,flow cytometry and Western blot,***18 methylation levels were determined by methylation-specific polymerase chain ***18,fibronectin(FN),type I collagen(Col-I)and alpha-smooth muscle actin(α-SMA)mRNA and protein expressions were analyzed by real-time PCR(RT-PCR)and Western blot,***,cells were treated with 50 mmol/L 5-aza-2′-deoxycytidine(5-aza-dC,demethylation agent)for 72 *** of curcumin on extracellular matrix(ECM)deposition was evaluated by immunochemical staining and Western ***-49F cells were transfected with ADAMTS18 small interfering RNA and grouped into a normal control,ADAMTS18-knock-out(KO),and ADAMTS18-KO+30μmol/L curcumin groups,and whether curcumin can reverse the effect of ADAMTS18 knockdown on RIF was *** Compared with the control group,TGF-β1 significantly inhibited the proliferation of NRK-49F cells,blocked the G1/G0 phase,promoted cell apoptosis and inhibited cyclin D1 expression(P<0.01).Among the different concentrations of curcumin,30μmol/L curcumin significantly reversed these processes(P<0.01).Immunochemical staining and Western blot results showed that curcumin significantly inhibited the deposition of FN,Col-I andα-SMA(P<0.01).Curcumin and 5-zaz-dC had synergistic effects,promoting ADAMTS18 expression,removing ADAMTS18 methylation,and reducing ECM ***18 knockdown promoted ECM accumulation,and curcumin reversed this process(P<0.01).Conclusion TGF-β1-induced fibrosis in NRK-49F ***

关键词： renal fibrosis curcumin Chinese medicine ADAMTS18 methylation modification

WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling

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International Journal of Oral Science 2024年第1期16卷 85-96页

作者： Qingling Huang Yi Xiao Ting Lan Youguang Lu Li Huang Dali Zheng department of Biochemistry and Molecular Biology School of Basic Medical SciencesFujian Medical UniversityFuzhouChina Fujian Key Laboratory of Oral Diseases School and Hospital of StomatologyFujian Medical UniversityFuzhouChina department of Preventive Dentistry School and Hospital of StomatologyFujian Medical UniversityFuzhouChina department of Dentistry The First Affiliated Hospital of Fujian Medical UniversityFuzhouChina

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor *** findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

关键词： WNT squamous tumorigenesis

How has the COVID-19 pandemic changed treatment preferences of patients with proximal ureteral stones?

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Surgical approach affecting long-term urinary continence status after robot-assisted laparoscopic prostatectomy prospectively evaluated using self-reported functional status(Expanded Prostate Cancer Index Composite,EPIC-26)

当代泌尿学（英文） 2024年第1期18卷 66-70页

作者： Ali Kaan Yildiz Ahmet Varan Hakan Kurt Omer Gokhan Doluoglu Berat Cem Ozgur department of urology University of Medical SciencesAnkara Training and Research HospitalAnkaraTurkey

Background:The impact of the coronavirus disease 2019(COVID-19)pandemic on patient decision making remains *** study aimed to investigate the effect of the pandemic on treatment preferences of patients with proximal ureteral stones.Materials and methods:Retrospective data regarding treatment preferences of patients diagnosed with symptomatic proximal ure-teral stones between July 2018 and November 2021 at a single center were *** from 493 patients were analyzed according to 2 groups,including patients diagnosed during the COVID-19 pandemic and those diagnosed during an equivalent period of time be-fore the pandemic.Results:Preference for conservative treatment increased during the COVID-19 pandemic(p=0.009).In patients who had previously undergone shock wave lithotripsy(SWL),the preference for SWL decreased and the preference for conservative treatment increased during the COVID-19 pandemic(p=0.042).Multiple logistic regression analysis revealed a significant correlation between a preference for conservative treatment during the pandemic and no prior spontaneous stone passage(p=0.003;odds ratio[OR],2.48;95％con-fidence interval[CI],1.45-4.23),no hydronephrosis(p=0.035;OR,3.57;95％Cl,1.34-9.49),and a visual analog scale score of 4 or less(p=0.018;OR,1.97;95％Cl,1.15-3.38).Conclusions:A significant increase in the preference for conservative treatment was observed among patients diagnosed during the pandemic,and patients with a history of SWL demonstrated a preference shift from SWL to conservative treatment.

关键词： COVID-19 pandemic Treatment preference Ureter Urolithiasis

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Thrombotic microangiopathy after kidney transplantation: Expanding etiologic and pathogenetic spectra

当代泌尿学（英文） 2024年第1期18卷 61-65页

作者： Mathias Reichert Ame Strauß Joost Wilhelm Voß Hans Christoph von Knobloch Hannah Maria Neuenhofer Annemarie Uhlig Lutz Trojan Mirjam Naomi Mohr department of urology University Medical CenterGoettingenGermany department of Pediatrics University HospitalBonnGermany

Purpose:The aim of the study was to examine the influence of the surgical approach for robot-assisted laparoscopic prostatectomy(RALP)on long-term urinary continence status in the era of self-reported functional status measures using the Expanded Prostate Can-cer Index Composite 26.Materials and methods:This is a prospective evaluation of 232 patients undergoing RALP between September,2019 and September,*** continence status and postoperative incontinence(pad usage)were evaluated 12 months after RALP using Expanded Prostate Cancer Index Composite 26 *** were categorized according to their surgical approach and outcome into the following groups:successful nerve sparing(NS),primarily without nerve sparing(***),and no nerve sparing by secondary resection(NNS by SR).The median levels of their questionnaire outcomes were evaluated and compared using the Wilcoxon rank sum test with continuity correction.Results:Urinary continence status 12 months after RALP differed significantly between the NS and ***(p=0.0071)and the NS and NNS by SR(p=0.0076)*** was no significant difference between the *** and NNS by SR(p=0.53)*** usage 12 months after RALP had no significant difference with regard to SR of the neurovascular bundle(p=0.14).Conclusions:Patient-reported outcomes of long-term urinary continence status seem to show no difference in postoperative conti-nence,regardless of whether a non-nerve-sparing result was planned or reached through ***,preservation of neurovascular bundle seems to lead to better long-term continence rates.

关键词： Expanded Prostate Cancer Index Composite 26 Nerve sparing Prostate cancer Robot-assisted radical prostatectomy Surgical approach Urinary incontinence

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World Journal of Transplantation 2024年第1期14卷 84-95页

作者： Muhammed Mubarak Amber Raza Rahma Rashid Fnu Sapna Shaheera Shakeel department of Histopathology Sindh Institute of Urology and TransplantationKarachi 74200SindhPakistan department of Nephrology Sindh Institute of Urology and TransplantationKarachi 74200SindhPakistan department of Pathology Montefiore Medical CenterThe University Hospital for Albert Einstein School of MedicineBronxNY 10461United States

Thrombotic microangiopathy(TMA)is an uncommon but serious complication that not only affects native kidneys but also transplanted *** review is specifically focused on post-transplant TMA(PT-TMA)involving kidney transplant *** reported prevalence in the latter population varies from 0.8%to 14%with adverse impacts on both graft and patient *** has many causes and associations,and the list of etiologic agents and associations is growing *** pathogenesis is equally varied and a variety of pathogenetic pathways lead to the development of microvascular injury as the final common ***-TMA is categorized in many ways in order to facilitate its ***,more than one causes are contributory in PT-TMA and it is often difficult to pinpoint one particular cause in an individual ***,the hallmark lesions are endothelial cell injury and intravascular thrombi affecting the *** diagnosis and classification of PT-TMA are imperative for optimal outcomes but are challenging for both clinicians and *** Banff classification has addressed this issue and has developed minimum diagnostic criteria for pathologic diagnosis of PT-TMA in the first *** of the condition is also challenging and still largely *** varies from simple maneuvers,such as plasmapheresis,drug withdrawal or modification,or dose reduction,to lifelong complement blockade,which is very expensive.A thorough understanding of the condition is imperative for an early diagnosis and quick treatment when the treatment is potentially *** review aims to increase the awareness of relevant stakeholders regarding this important,potentially treatable but under-recognized cause of kidney allograft dysfunction.

关键词： Thrombotic microangiopathy Microvascular injury Anemia Thrombocytopenia Kidney allograft failure

Current devices,outcomes,and pain management considerations in penile implant surgery:an updated review of the literature

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Asian Journal of Andrology 2024年第4期26卷 335-343页

作者： Nirupama Ancha Maya Eldin Tarah Woodle Sofia Gereta Krishna Hariprasad Imani Butler E Charles Osterberg III department of Surgery and Perioperative Care University of Texas at Austin Dell Medical SchoolAustinTX 78712USA department of urology Brooke Army Medical CenterSan AntonioTX 78234USA department of Molecular Biosciences The University of Texas at AustinAustinTX 78712USA.

Penile prosthesis surgery is a definitive treatment for erectile dysfunction(ED).The two categories of penile prosthesis are endorsed by professional guidelines,inflatable penile prosthesis(IPP)and malleable penile prosthesis(MPP).Each modality of penile prosthesis offers distinct advantages and incorporates specific design features,allowing for personalized device selection that aligns with individual needs and *** the overall complication rate of penile implant surgery remains low,surgeons should maintain a high index of suspicion for complications in the perioperative time *** analgesic regimens including nerve blocks and narcotic-free pathways should be administered to manage perioperative ***,the high patient satisfaction after penile prosthesis surgery underscores the success of this ED treatment option.

关键词： erectile dysfunction penile implant penile prosthesis

Transperineal laser ablation of the prostate as a treatment for benign prostatic hyperplasia and prostate cancer: The results of a Delphi consensus project

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Asian Journal of urology 2024年第2期11卷 271-279页

作者： Andrea Cocci Marta Pezzoli Fernando Bianco Franco Blefari Pierluigi Bove Francois Cornud Gaetano De Rienzo Paolo Destefanis Danilo Di Trapani Alessandro Giacobbe Luca Giovanessi Antonino Laganà Giovanni Lughezzani Guglielmo Manenti Gianluca Muto Gianluigi Patelli Novello Pinzi Stefano Regusci Giorgio I.Russo Juan I.M.Salamanca Matteo Salvi Luigi Silvestri Fabrizio Verweij Eric Walser Riccardo GBertolo Valerio Iacovelli Alessandro Bertaccini Debora Marchiori Hugo Davila Pasquale Ditonno Paolo Gontero Gennaro Iapicca Theo M De Reijke Vito Ricapito Pierluca Pellegrini Andrea Minervini Sergio Serni Francesco Sessa department of urology Careggi HospitalUniversity of FlorenceFlorenceItaly urology Section University of FlorenceFlorenceItaly Urological Research Network MiamiFLUSA urology Section Prato HospitalPratoItaly Torvergata Oncoscience Research Centre of Excellence TORDepartment of Experimental MedicineUniversity of Rome Tor VergataRomeItaly department of urology San Carlo di Nancy HospitalRomeItaly department of Radiology Hôpital CochinParis Descartes UniversityParisFrance urology and Andrology Unit II Department of Emergency and Organ TransplantationUniversity of BariBariItaly Unit of urology Cittàdella Salute e della Scienza HospitalUniversity of TurinTurinItaly urology Unit Buccheri La Ferla Fatebenefratelli HospitalPalermoItaly department of urology Humanitas Gradenigo HospitalTurinItaly urology Unit Surgical DepartmentFondazione Poliambulanza Istituto OspedalieroBresciaItaly Departement of urology “S.Giovanni Evangelista”HospitalTivoliItaly Humanitas Clinical and Research CentereIRCCS Department of UrologyRozzanoItaly department of Biomedical Sciences Humanitas UniversityPieve EmanueleItaly department of Biomedicine and Prevention University of Rome“Tor Vergata”RomeItaly department of Diagnostic Imaging and Interventional Radiology University of Rome“Tor Vergata”RomeItaly department of Interventional Radiology Pesenti-Fenaroli Hospital-ASST Bergamo EstAlzano LombardoItaly department of urology University of SienaSienaItaly Swiss International Prostate Center GenevaSwitzerland Clinique Générale Beaulieu GenevaSwitzerland department of urology University of CataniaItaly department of urology Puerta de Hierro-Majadahonda University HospitalMadridSpain Lyx Institute of urology Universidad Francisco de VitoriaMadridSpain department of Medico-Surgical Sciences and Biotechnologies Sapienza University of RomeFaculty of Pharmacy and MedicineUrology Unit ICOTLatinaItaly department of urology European Institute of Oncology(IEO)IRCCSMilanItaly department of Radiology D

Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using the Delphi consensus ***: Italian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and ***: Thirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from 80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading t

关键词： Transperineal laser ablation Prostatecancer Benignprostatic hyperplasia Delphi consensus