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Magnesium lithospermate B enhances the potential of human-induced pluripotent stem cell-derived cardiomyocytes for myocardial repair

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中华医学杂志(英文版) 2024年第15期137卷 1857-1869页

作者： Fan Chengming Qin Kele Iroegbu Chukwuemeka Daniel Xiang Kun Gong Yibo Guan Qing Wang Wenxiang Peng Jun Guo Jianjun Wu Xun Yang Jinfu department of Cardiovascular Surgery The Second Xiangya Hospital Central South University Changsha Hunan China department of Pharmacology Xiangya School of Pharmaceutical Sciences Central South University Changsha Hunan China Hunan Fangsheng Pharmaceutical Co. Ltd. Changsha Hunan China department of Thoracic Surgery The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha Hunan China

Background: We previously reported that activation of the cell cycle in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enhances their remuscularization capacity after human cardiac muscle patch transplantation in infarcted mouse hearts. Herein, we sought to identify the effect of magnesium lithospermate B (MLB) on hiPSC-CMs during myocardial repair using a myocardial infarction (MI) mouse ***: In C57BL/6 mice, MI was surgically induced by ligating the left anterior descending coronary artery. The mice were randomly divided into five groups (n = 10 per group); a MI group (treated with phosphate-buffered saline only), a hiPSC-CMs group, a MLB group, a hiPSC-CMs + MLB group, and a Sham operation group. Cardiac function and MLB therapeutic efficacy were evaluated by echocardiography and histochemical staining 4 weeks after surgery. To identify the associated mechanism, nuclear factor (NF)-κB p65 and intercellular cell adhesion molecule-1 (ICAM1) signals, cell adhesion ability, generation of reactive oxygen species, and rates of apoptosis were detected in human umbilical vein endothelial cells (HUVECs) and ***: After 4 weeks of transplantation, the number of cells that engrafted in the hiPSC-CMs + MLB group was about five times higher than those in the hiPSC-CMs group. Additionally, MLB treatment significantly reduced tohoku hospital pediatrics-1 (THP-1) cell adhesion, ICAM1 expression, NF-κB nuclear translocation, reactive oxygen species production, NF-κB p65 phosphorylation, and cell apoptosis in HUVECs cultured under hypoxia. Similarly, treatment with MLB significantly inhibited the apoptosis of hiPSC-CMsvia enhancing signal transducer and activator of transcription 3 (STAT3) phosphorylation and B-cell lymphoma-2 (BCL2) expression, promoting STAT3 nuclear translocation, and downregulating BCL2-Associated X, dual specificity phosphatase 2 (DUSP2), and cleaved-caspase-3 expression under hypoxia. Furthermore, MLB significan

关键词： Myocardial infarction Cell therapy Induced pluripotent stem cells Magnesium lithospermate B Cardiomyocyte Disease modeling hiPSC-CMs

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Recent advancements in the diagnosis and treatment of acral melanoma

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2024年第2期25卷 106-122页

作者： Ahmad ALHASKAWI Sohaib Hasan Abdullah EZZI Yanzhao DONG Haiying ZHOU Zewei WANG Jingtian LAI Chengjun YAO Vishnu Goutham KOTA Mohamed Hasan Abdulla Hasan ABDULLA Hui LU department of Orthopedics the First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou310003China department of Orthopaedics Third Xiangya HospitalCentral South UniversityChangsha410013China Zhejiang university School of Medicine Hangzhou310058China Alibaba-Zhejiang university Joint Research Center of Future Digital Healthcare Zhejiang UniversityHangzhou310058China

Acral melanoma(AM)is the most common histologic subtype of melanoma in dark-skinned patients and is associated with a worse prognosis and a high mortality rate,largely due to the inconspicuous nature of early-stage lesions,which can lead to late *** of the overlapping clinical and histopathological features of AM with other forms of cutaneous melanomas,early detection of AM requires a multidisciplinary approach that integrates various diagnostic modalities,including clinical examination,dermoscopy,histopathology,molecular testing,radiological imaging,and blood *** surgery is the preferred method of treatment for AM,other therapeutic options may be employed based on the stage and underlying etiology of the *** checkpoint inhibitors,molecular targeted therapy,radiotherapy,chemotherapy,and oncolytic virotherapy represent promising advanced treatment options for *** this review,we provide an overview of the latest advancements in diagnostic and therapeutic methods for AM,highlighting the importance of early detection and the prompt,individualized management of this challenging disease.

关键词： Acral melanoma Acral lentiginous melanoma Acral nevus Cutaneous malignant melanoma Dermoscopy Oncolytic virotherapy

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Viral-mediated gene therapy in pediatric neurological disorders

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World Journal of Pediatrics 2024年第6期20卷 533-555页

作者： Jing Peng Wei-Wei Zou Xiao-Lei Wang Zhi-Guo Zhang Ran Huo Li Yang department of Pediatrics Clinical Research Center for Chidren Neurodevelopmental disablities of Hunan ProvinceXiangya HospitalCentral South UniversityChangsha 410008China Reproductive Medicine Center Department of Obstetrics and Gynecologythe First Affiliated Hospital of Anhui Medical UniversityHefeiChina State Key Laboratory of Reproductive Medicine Nanjing Medical UniversityNanjingChina

Background Due to the broad application of next-generation sequencing,the molecular diagnosis of genetic disorders in pediatric neurology is no longer an unachievable ***,treatments for neurological genetic disorders in children remain primarily *** the other hand,with the continuous evolution of therapeutic viral vectors,gene therapy is becoming a clinical *** this perspective,we wrote this review to illustrate the current state regarding viral-mediated gene therapy in childhood neurological *** sources We searched databases,including PubMed and Google Scholar,using the keywords"adenovirus vector,""lentivirus vector,"and"AAv"for gene therapy,and"immunoreaction induced by gene therapy vectors,""administration routes of gene therapy vectors,"and"gene therapy"with"NCL,""SMA,""DMD,""congenital myopathy,""MPS""leukodystrophy,"or"pediatric metabolic disorders".We also screened the database of *** using the keywords"gene therapy for children"and then filtered the results with the ones aimed at neurological *** time range of the search procedure was from the inception of the databases to the *** We presented the characteristics of commonly used viral vectors for gene therapy for pediatric neurological disorders and summarized their merits and drawbacks,the administration routes of each vector,the research progress,and the clinical application status of viral-mediated gene therapy on pediatric neurological *** Viral-mediated gene therapy is on the brink of broad clinical ***-mediated gene therapy will dramatically change the treatment pattern of childhood neurological disorders,and many children with incurable diseases will meet the dawn of a ***,the vectors must be optimized for better safety and efficacy.

关键词： Gene therapy Neurological disorders Pediatrics Viral vectors

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Engineering self-catabolic DNAzyme nanospheres for synergistic anticancer therapy

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Science China Chemistry 2024年第7期67卷 2412-2422页

作者： Yu Chen Yu Guo Jiaoli Wang Ruiting Liu Xiaohai Yang Kemin Wang Ying Pu Hui Shi Jin Huang Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical EngineeringKey Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan ProvinceHunan UniversityChangsha 410082China National Clinical Research Center for Geriatric Disorders Department of GeriatricsXiangya HospitalCentral South UniversityChangsha 410008China

DNAzyme-based gene therapy faces some challenges including cell penetration,activity limitation,and co-delivery ***-assembled DNA nanomedicine has attracted widespread attention due to its many *** is urgent to develop a universal DNA degradation strategy for precise programmable drug ***,we reported a self-catabolic DNAzyme nanospheres(SCNS),which could simultaneously achieve cell penetration,activity enhancement,and co-delivery *** SCNS were assembled through Y-DNA stepwise hybridization with each other,which were then loaded with aptamer(Apt),doxorubicin(Dox),and zinc oxide nanoparticles(ZnO NPs).The acid-triggered dissociation of ZnO NPs leads to the generation of Zn^(2+)ions cofactors for immediately self-catabolic DNAzyme *** the disassembly of the SCNS,three types of anticancer treatments would be activated,which include Zn^(2+)involved reactive oxygen species(ROS),Dox-induced chemotherapy,and DNAzyme-based gene *** experimental results show that the nanoplatform(Apt-SCNS-Dox-ZnO)has a good tumor-killing effect and minimal side *** a smart self-driven drug delivery nanoplatform,it is anticipated to displace extraordinary potential in biomedicine and bioengineering.

关键词： DNAzyme nanosphere ZnO NPs ROS Dox anticancer therapy

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Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx

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Bone Research 2024年第2期12卷 334-348页

作者： Ziqian Xiang Pengfei Zhang Chunwang Jia Rongkun Xu Dingren Cao Zhaoning Xu Tingting Lu Jingwei Liu Xiaoxiong Wang Cheng Qiu Wenyang Fu Weiwei Li Lei Cheng Qiang Yang Shiqing Feng Lianlei Wang Yunpeng Zhao Xinyu Liu department of Orthopaedics Qilu Hospital of Shandong UniversityJinan 250012China university of Health and Rehabilitation Sciences Qingdao 226000China xiangya School of Medicine Central South UniversityChangsha 410013China School of Nursing and Rehabilitation Shandong UniversityJinan 250012China department of Pediatrics Cangzhou Central HospitalCangzhou 061011China department of Pediatric Surgery Qilu Hospital of Shandong UniversityJinan 250012China department of Pathology Qilu Hospital of Shandong UniversityJinan 250012China department of Spine Surgery Tianjin HospitalTianjin UniversityTianjin 30021China The Second hospital of Shandong university Cheeloo College of MedicineShandong UniversityJinan 250012China

To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be ***,Piezo1 channel was identified as a key iron transporter in response to mechanical ***1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells(NPCs).Importantly,Piezo1-induced iron influx was independent of the transferrin receptor(TFRC),a well-recognized iron ***,pharmacological inactivation of Piezo1 profoundly reduced iron accumulation,alleviated mitochondrial ROS,and suppressed ferroptotic alterations in stimulation of mechanical ***,conditional knockout of Piezo1(Col2a1-CreERT Piezo1^(flox/flox))attenuated the mechanical injury-induced intervertebral disc degeneration(IVDD).Notably,the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout(cDKO)mice(Col2a1-CreERT Piezo1^(flox/flox)/Gpx4^(flox/flox)).These findings suggest that Piezo1 is a potential determinant of iron influx,indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.

关键词： stress overload channel

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Development of a clinical nomogram for prediction of response to neoadjuvant chemotherapy in patients with advanced gastric cancer

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 396-408页

作者： Bing Liu Yu-Jie Xu Feng-Ran Chu Guang Sun Guo-Dong Zhao Sheng-Zhong Wang department of Gastrointestinal Surgery Central South University Xiangya School of Medicine Affiliated Haikou HospitalHaikou 570208Hainan ProvinceChina Clinical College Hainan Medical UniversityHaikou 571199Hainan ProvinceChina

BACKGROUND The efficacy of neoadjuvant chemotherapy(NAC)in advanced gastric cancer(GC)is still a controversial *** To find factors associated with chemosensitivity to NAC treatment and to provide the optimal therapeutic strategies for GC patients receiving *** The clinical information was collected from 230 GC patients who received NAC treatment at the central south university xiangya School of Medicine Affiliated Haikou hospital from January 2016 to December *** absolute shrinkage and selection operator logistic regression analysis was used to find the possible predictors.A nomogram model was employed to predict the response to *** In total 230 patients were finally included in this study,including 154 males(67.0%)and 76 females(33.0%).The mean age was(59.37±10.60)years,ranging from 24 years to 80 *** to the tumor regression grade standard,there were 95 cases in the obvious response group(grade 0 or grade 1)and 135 cases in the poor response group(grade 2 or grade 3).The obvious response rate was 41.3%.Least absolute shrinkage and selection operator analysis showed that four risk factors significantly related to the efficacy of NAC were tumor location(P<0.001),histological differentiation(P=0.001),clinical T stage(P=0.008),and carbohydrate antigen 724(P=0.008).The C-index for the prediction nomogram was *** calibration curve revealed that the predicted value exhibited good agreement with the actual *** curve analysis showed that the nomogram had a good value in clinical *** A nomogram combining tumor location,histological differentiation,clinical T stage,and carbohydrate antigen 724 showed satisfactory predictive power to the response of NAC and can be used by gastrointestinal surgeons to determine the optimal treatment strategies for advanced GC patients.

关键词： Advanced gastric cancer Predictor Neoadjuvant chemotherapy Nomogram Tumor regression grade

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Attention Guided Multi Scale Feature Fusion Network for Automatic Prostate Segmentation

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Computers, Materials & Continua 2024年第2期78卷 1649-1668页

作者： Yuchun Li Mengxing Huang Yu Zhang Zhiming Bai School of Information and Communication Engineering Hainan UniversityHaikouChina College of Computer Science and Technology Hainan UniversityHaikouChina Urology department Haikou Municipal People’s Hospital and Central South University Xiangya Medical College Affiliated HospitalHaikouChina School of Information Science and Technology Hainan Normal UniversityHaikouChina

The precise and automatic segmentation of prostate magnetic resonance imaging(MRI)images is vital for assisting doctors in diagnosing prostate *** recent years,many advanced methods have been applied to prostate segmentation,but due to the variability caused by prostate diseases,automatic segmentation of the prostate presents significant *** this paper,we propose an attention-guided multi-scale feature fusion network(AGMSF-Net)to segment prostate MRI *** propose an attention mechanism for extracting multi-scale features,and introduce a 3D transformer module to enhance global feature representation by adding it during the transition phase from encoder to *** the decoder stage,a feature fusion module is proposed to obtain global context *** evaluate our model on MRI images of the prostate acquired from a local *** relative volume difference(RVD)and dice similarity coefficient(DSC)between the results of automatic prostate segmentation and ground truth were 1.21%and 93.68%,*** quantitatively evaluate prostate volume on MRI,which is of significant clinical significance,we propose a unique *** essential performance evaluation and validation experiments have demonstrated the effectiveness of our method in automatic prostate segmentation.

关键词： Prostate segmentation multi-scale attention 3D Transformer feature fusion MRI

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Editorial:Transcriptome analysis in tumor microenvironment and tumor heterogeneity

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Oncology Research 2024年第1期32卷 99-100页

作者： JINHUI LIU JIAHENG XIE PEIXIN DONG department of Gynecology The First Affiliated Hospital of Nanjing Medical UniversityNanjing210029China department of Plastic and Cosmetic Surgery Xiangya HospitalCentral South UniversityChangsha410008China department of Obstetrics and Gynecology Hokkaido University School of MedicineHokkaido UniversitySapporo060-8638Japan

Cancer,a disease as intricate as it is devastating,continues to challenge the medical and scientific community[1].Its complex nature is epitomized by the tumor microenvironment and tumor *** we delve deeper into the realms of cancer research,the advent of transcriptome analysis has emerged as a powerful torchbearer,illuminating our understanding of these enigmatic facets of cancer biology[2].

关键词： heterogeneity. tumor Cancer

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Changes in visual performance after implantation of different intraocular lenses

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1273-1282页

作者： Bo-Wen Li Hao Huang Man-Sha Huang Shuang-Lin Guo Lu Gao Yu-Ying Zeng Lu Cheng Si-Yang Yao Jian-Qiang Lin Lin Liu Ye Yang Xiao-Ming Lu Hao Cheng department of Ophthalmology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityGuangzhou 510000Guangdong ProvinceChina Eye Center of xiangya hospital Hunan Key Laboratory of OphthalmologyCentral South UniversityChangsha 410008Hunan ProvinceChina department of Ophthalmology Zhuzhou Hospital Affiliated to Xiangya School of MedicineCentral South UniversityZhuzhou 412000Hunan ProvinceChina State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangzhou 510060Guangdong ProvinceChina department of Ophthalmology Guangzhou Red Cross HospitalJinan UniversityGuangzhou 510000Guangdong ProvinceChina AIER Eye hospital Jinan UniversityGuangzhou 510180Guangdong ProvinceChina

AIM:To evaluate the trending visual performance of different intraocular lenses(IOLs)over time after ***:Ninety-one patients received cataract surgery with implantations of monofocal(Mon)IOLs,segmental refractive(SegRef)IOLs,diffractive(Dif)IOLs,and extendeddepth-of-focus(EDoF)IOLs were *** aberrations and optical quality collected with iTrace and OQAS within postoperative 6mo were followed and ***:Most of the visual parameters improved over the postoperative *** postoperative visual acuity(POVA)of the Mon IOL,SegRef IOL,and EDoF IOL groups achieved relative stability in earlier states compared with the Dif IOL ***,the overall visual performance of the 3 IOLs continued to upturn in small extents within the postoperative *** optical quality initially improved in the EDoF IOL group,then in the Mon IOL,SegRef IOL,and Dif IOL *** and objective visual performance of the Mon IOL and EDoF IOL groups,as well as POVA and visual quality of the Dif IOL group,improved in the postoperative 1mo and *** the postoperative 6mo,gradual improvements were observed in the visual acuity and objective visual performance of the SegRef IOL group,as well as in the postoperative optical quality of the Dif IOL ***:The visual performance is different among eyes implanted with different *** findings of the current study provide a potential reference for ophthalmologists to choose suitable IOLs for cataract patients in a personalized solution.

关键词： intraocular lenses visual performance changing characteristics high-order wavefront aberration

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A Cullin 5-based complex serves as an essential modulator of ORF9b stability in SARS-CoV-2 replication

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3112-3129页

作者： Yuzheng Zhou Zongpeng Chen Sijie Liu Sixu Liu Yujie Liao Ashuai Du Zijun Dong Yongxing Zhang Xuan Chen Siyi Tao Xin Wu Aroona Razzaq Gang Xu De-an Tan Shanni Li Youwen Deng Jian Peng Shuyan Dai Xu Deng Xianwen Zhang Taijiao Jiang Zheng Zhang Gong Cheng Jincun Zhao Zanxian Xia department of Cell Biology School of Life SciencesCentral South University410013 ChangshaChina Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People’s HospitalThe Second Affiliated HospitalSchool of MedicineSouthern University of Science and Technology518112 ShenzhenChina department of Basic Medicine School of MedicineHunan Normal University410081 ChangshaChina department of spine surgery The Third Xiangya HospitalCentral South University410013 ChangshaChina School of Basic Medical Sciences Anhui Medical University230032 HefeiChina Hunan Key Laboratory of Neurorestoratology 921 Hospital of Joint Logistics Support Force People’s Liberation Army of China(The Second Affiliated Hospital of Hunan Normal University)410003 ChangshaHunanChina department of Geriatric Surgery Xiangya HospitalCentral South University410008 ChangshaChina xiangya School of Pharmaceutical Sciences Central South University410013 ChangshaChina Institute of Infectious Diseases Shenzhen Bay Laboratory518132 ShenzhenChina Guangzhou Laboratory 510005 GuangzhouChina Tsinghua university-Peking university Joint Center for Life Sciences School of MedicineTsinghua University100084 BeijingChina State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical University510120 GuangzhouChina Hunan Key Laboratory of Animal Models for Human Diseases Hunan Key Laboratory of Medical Genetics&Center for Medical GeneticsSchool of Life SciencesCentral South University410008 ChangshaChina

The ORF9b protein,derived from the nucleocapsid’s open-reading frame in both SARS-CoV and SARS-CoV-2,serves as an accessory protein crucial for viral immune evasion by inhibiting the innate immune *** its significance,the precise regulatory mechanisms underlying its function remain *** the present study,we unveil that the ORF9b protein of SARS-CoV-2,including emerging mutant strains like Delta and Omicron,can undergo ubiquitination at the K67 site and subsequent degradation via the proteasome pathway,despite certain mutations present among these ***,our investigation further uncovers the pivotal role of the translocase of the outer mitochondrial membrane 70(TOM70)as a substrate receptor,bridging ORF9b with heat shock protein 90 alpha(HSP90α)and Cullin 5(CUL5)to form a *** this complex,CUL5 triggers the ubiquitination and degradation of ORF9b,acting as a host antiviral factor,while HSP90αfunctions to stabilize ***,treatment with HSP90 inhibitors such as GA or 17-AAG accelerates the degradation of ORF9b,leading to a pronounced inhibition of SARS-CoV-2 ***-cell sequencing data revealed an up-regulation of HSP90αin lung epithelial cells from COVID-19 patients,suggesting a potential mechanism by which SARS-CoV-2 may exploit HSP90αto evade the host *** study identifies the CUL5-TOM70-HSP90αcomplex as a critical regulator of ORF9b protein stability,shedding light on the intricate host–virus immune response dynamics and offering promising avenues for drug development against SARS-CoV-2 in clinical settings.

关键词： stability modulator offering

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