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New evidence for the epigenetic regulation of skeletal stem cells

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Science Bulletin 2024年第13期69卷 2004-2006页

作者： Liming Zhao Jun Xiao Charles K.F.Chan Institute for Stem Cell Biology and Regenerative medicine Stanford University School of MedicineStanford CA 94305USA department of surgery Division of Plastic and Reconstructive SurgeryStanford University School of MedicineStanford CA 94305USA department of Orthopaedic surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Skeletal stem cells(SSCs)are crucial for skeletal development and regeneration,yet the epigenetic regulation of these cells remains poorly *** studies have delineated the epigenetic landscape across the developmental trajectory of SSCs,highlighting the involvement of Ptip in regulating SSC *** skeletal system undergoes dynamic remodeling throughout *** stem cells(SSCs),residing within the skeleton and lineage-restricted,serve as a cellular reserve to foster development and maintain skeletal *** categorized within the broader mesenchymal stromal/stem cells(MSCs).

关键词： skeletal involvement maintain

Addressing the alarming link between nonalcoholic fatty liver disease and cardiovascular mortality in men

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World Journal of Cardiology 2024年第9期16卷 502-507页

作者： Wen-Rui Hao Chun-Han Cheng Tzu-Hurng Cheng Division of Cardiology Department of Internal MedicineShuang Ho HospitalMinistry of Health and WelfareTaipei Medical UniversityNew Taipei 23561TaiwanChina Division of Cardiology Department of Internal MedicineSchool of MedicineCollege of MedicineTaipei Medical UniversityTaipei 11002TaiwanChina department of medical Education Linkou Chang Gung Memorial HospitalTaoyuan 33305TaiwanChina department of Biochemistry School of MedicineCollege of MedicineChina Medical UniversityTaichung 404328TaiwanChina

This editorial discusses the key findings presented in Batta and Hatwal’s recent paper titled“Excess cardiovascular mortality in men with non-alcoholic fatty liver disease:A cause for concern!”,which was published in the World Journal of *** original article highlights a notable correlation between nonalcoholic fatty liver disease(NAFLD)and increased cardiovascular mortality risk in *** present commentary explores the implications of their findings,discussing potential mechanisms,risk factors,and the urgent need for integrated clinical approaches to mitigate the dual burden of these *** should be placed on the importance of early detection,lifestyle modifications,and interdisciplinary collaboration for improving patient *** editorial aims to highlight the broad implications of NAFLD for cardiovascular health and to advocate for increased awareness and proactive management strategies within the medical community.

关键词： Non-alcoholic fatty liver disease Cardiovascular mortality Men's health Integrated clinical approaches Risk factors

Investigating clubfoot in Saudi Arabia: Prevalence, factors, and future directions

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World Journal of Orthopedics 2024年第9期15卷 836-840页

作者： Chun-Han Cheng Wen-Rui Hao Tzu-Hurng Cheng department of medical Education Linkou Chang Gung Memorial HospitalTaoyuan 33305Taiwan Division of Cardiology Department of Internal MedicineShuang Ho HospitalMinistry of Health and WelfareTaipei Medical UniversityNew Taipei 23561Taiwan Division of Cardiology Department of Internal MedicineSchool of MedicineCollege of MedicineTaipei Medical UniversityTaipei 11002Taiwan department of Biochemistry School of MedicineCollege of MedicineChina Medical UniversityTaichung 404328Taiwan

This editorial discusses the significant findings and implications of the study conducted by Alomran et *** retrospective study,soon to be published,provides valuable insights into the epidemiology of and risk factors associated with clubfoot in a specific Saudi *** highlighting the study’s key outcomes and discussing its broader implications for public health and clinical practices,this editorial aims to underscore the importance of continued research and targeted interventions in addressing congenital deformities such as clubfoot.

关键词： Clubfoot prevalence Saudi Arabia Congenital deformities Retrospective study Orthopedic epidemiology

Mesenchymal stem cells: A promising therapeutic avenue for nonalcoholic fatty liver disease

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World Journal of Stem Cells 2024年第8期16卷 780-783页

Non-alcoholic fatty liver disease(NAFLD)is a pressing global health concern that is associated with metabolic syndrome and *** the basis of the insights provided by Jiang et al,this editorial presents an exploration of the potential of mesenchymal stem cells(MSCs)for NAFLD *** have numerous desirable characteristics,including immunomodulation,anti-inflammatory pro-perties,and tissue regeneration promotion,rendering them attractive candidates for NAFLD *** preclinical and early clinical studies have high-lighted the efficacy of MSCs in improving liver function and reducing disease severity in NAFLD ***,MSC heterogeneity,long-term safety concerns,and unoptimized therapeutic protocols remain substantial *** these challenges through standardized protocols and rigorous clinical trials is essential to the safe and successful application of MSCs in NAFLD *** research into MSC mechanisms and therapeutic optimization is required to improve treatments for NAFLD and related liver diseases.

关键词： Mesenchymal stem cells Non-alcoholic fatty liver disease Therapeutic potential Liver fibrosis Regenerative medicine Stem cell therapy Inflammation Clinical trials

Understanding the global cancer statistics 2022: growing cancer burden

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Science China Life Sciences 2024年第10期67卷 2274-2276页

作者： Yuxi Liu Zhibo Zheng school of Basic medicine Shanghai Medical College Fudan University department of Thoracic surgery Department of International Medical ServicesPeking Union Medical College HospitalChinese Academy of Medical Sciences

The International Agency for Research on Cancer(IARC) established in 1965 as the cancer agency of the World Health Organization, focuses on cancer research and dedicates to developing strategies for cancer control glo...

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The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex C.Haydon Hue H.Luu Sherwin Ho Michael J.Lee Jason Strelzow Russell R.Reid Tong-Chuan He school of medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China department of Orthopedic surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Clinical Laboratory medicine Shanghai Jiaotong University School of MedicineShanghai 200000China department of Orthopaedic surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

Liposomalα-cyperone targeting bone resorption surfaces suppresses osteoclast differentiation and osteoporosis progression via the PI3K/Akt axis

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Nano Research 2024年第4期17卷 2949-2959页

作者： Lin Yang Xueying An Wang Gong Wenshu Wu Bin Liu Xiaoyan Shao Yansi Xian Rui Peng Baosheng Guo Qing Jiang Division of Sports medicine and Adult Reconstructive surgery Department of Orthopedic SurgeryNanjing Drum Tower Hospital Clinical College of Nanjing Medical University321 Zhongshan RoadNanjing 210008China Branch of National Clinical Research Center for Orthopedics Sports Medicine and RehabilitationNanjing 210008China State Key Laboratory of Pharmaceutical Biotechnology Medical SchoolNanjing University&Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

Osteoporosis is a metabolic dysregulation of bone that occurs mainly in postmenopausal women,and the hyperfunction of osteoclasts is the primary contributor to postmenopausal ***,the development of effective therapeutic drugs and precise delivery systems remains a challenge in the field of anti-absorption ***,we reported theα-cyperone(α-CYP)for anti-osteoporosis and developed a liposome-based nano-drug delivery system ofα-CYP,that specifically targets the bone resorption ***,we found that theα-CYP,one of the major sesquiterpenes of Cyperus rotundus L.,attenuated the progression of osteoporosis in ovariectomized(OVX)mice and down-regulated the expression of phosphorylated proteins of phosphoinositide 3-kinase(PI3K)and protein kinase B(Akt),causing down-regulation of osteoclast-related genes/proteins and curbing osteoclast ***,α-CYP reversed the activation of osteoclastic differentiation and enhanced osteoporosis-related proteins expression caused by PI3K/Akt agonist(YS-49).More importantly,we adopted the osteoclastic resorption surface targeting peptide Asp8 and constructed the liposome(lipαC@Asp8)to deliverα-CYP to osteoclasts and confirmed its anti-osteoporosis effect and enhanced osteoclast inhibition by blocking PI3K/Akt *** conclusion,this study demonstrated thatα-CYP inhibits osteoclast differentiation and osteoporosis development by silencing PI3K/Akt pathway,and the liposome targeting delivery systems loaded withα-CYP might provide a novel and effective strategy to treat osteoporosis.

关键词： osteoporosis α-cyperone osteoclast phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) liposome

Neural Wiskott-Aldrich syndrome protein(N-WASP)promotes distant metastasis in pancreatic ductal adenocarcinoma via activation of LOXL2

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Oncology Research 2024年第4期32卷 615-624页

作者： HYUNG SUN KIM YUN SUN LEE SEUNG MYUNG DONG HYO JUNG KIM DA EUN LEE HYEON WOONG KANG MYEONG JIN KIM JOON SEONG PARK department of surgery Gangnam Severance HospitalYonsei University College of MedicineSeoulKorea department of surgery Graduate School of Medical ScienceBrain Korea 21 ProjectYonsei University College of MedicineSeoulKorea Gibiome Co. Ltd.Gyeonggi-doKorea

Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive solid malignancies.A specific mechanism of its metastasis has not been *** this study,we investigated whether Neural Wiskott-Aldrich syndrome protein(N-WASP)plays a role in distant metastasis of *** found that N-WASP is markedly expressed in clinical patients with *** analysis showed a notably more distant metastatic pattern in the N-WASP-high group compared to the N-WASP-low group.N-WASP was noted to be a novel mediator of epithelialmesenchymal transition(EMT)via gene expression profile *** of N-WASP in pancreatic cancer cells significantly inhibited cell invasion,migration,and *** also observed positive association of lysyl oxidase-like 2(LOXL2)and focal adhesion kinase(FAK)with the N-WASP-mediated response,wherein EMT and invadopodia function were *** N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic *** results elucidate a novel role for N-WASP signaling associated with LOXL2 in EMT and invadopodia function,with respect to regulation of intercellular communication in tumor cells for promoting pancreatic cancer *** findings may aid in the development of therapeutic strategies against pancreatic cancer.

关键词： Pancreatic cancer Neural Wiskott-Aldrich syndrome protein(N-WASP)signaling Metastasis Epithelial-mesenchymal transition(EMT) Lysyl oxidase-like 2(LOXL2)

Quercetin inhibits truncated isoform of dopamine-and cAMP-regulated phosphoprotein as adjuvant treatment for trastuzumab therapy resistance in HER2-positive breast cancer

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Food Science and Human Wellness 2024年第5期13卷 2653-2667页

作者： Han-Sheng Chang Tzu-Chun Cheng Shih-Hsin Tu Chih-Hsiung Wu You-Cheng Liao Jungshan Chang Min-Hsiung Pan Li-Ching Chen Yuan-Soon Ho department of Biological Science&Technology College of Life SciencesChina Medical UniversityTaichung 406TaiwanChina Institute of Biochemistry and Molecular Biology College of Life SciencesChina Medical UniversityTaichung 406TaiwanChina department of surgery School of MedicineCollege of MedicineTaipei Medical UniversityTaipei 110TaiwanChina department of surgery Taipei Medical University HospitalTaipei 110TaiwanChina Graduate Institute of medical Sciences College of MedicineTaipei Medical UniversityTaipei 110TaiwanChina Institute of Food Sciences and Technology National Taiwan UniversityTaipei 106TaiwanChina

Trastuzumab resistance is one of the causes of poor prognosis in patients with human epidermal growth factor receptor 2(HER2)-positive(HER2+)breast cancer(BC).The truncated isoform of dopamine-and cAMPregulated phosphoprotein(t-DARPP)has been reported to be involved in trastuzumab therapy resistance and promoting tumor *** evaluate the t-DARPP expression in BC,paired tumors and surrounding normal tissues were analyzed by real-time polymerase chain reaction and confirmed higher DARPP-32 kDa family mRNA expression in HER2+BC tumor *** established 2 patient-derived xenografts(PDX)mice models to test the efficacy of trastuzumab,named model 1(non-responder)and model 2(responder).t-DARPP and p95-HER2 protein-protein interactions were detected in PDX tumor tissue from non-responders using Förster resonance energy transfer ***,there is no response from the ***,mechanistic studies using transwell and western blot assays demonstrated that t-DARPP could upregulate epithelial-mesenchymal transition signaling proteins,enhance p95-HER2 expression and promote cell *** found that quercetin effectively reduced t-DARPP expression in HER2+BC *** t-DARPP ShRNA-suppressed cells,quercetin synergistically enhanced trastuzumab-induced apoptotic cell death and G2/M phase *** conclusion,the combination of quercetin and trastuzumab treatment by targeting t-DARPP in HER2+BC patients has the potential as a biomarker for mitigating drug resistance.

关键词： p95-Human epidermal growth factor receptor 2 (HER2) HER2-positive breast cancer Quercetin Trastuzumab resistance Truncated isoform of dopamine-and cAMPregulated phosphoprotein