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Exploring the mechanism of Xiaoaiping Injection inhibiting autophagy in prostate cancer based on proteomics

Chinese Journal of Natural medicines 2025年第1期23卷 64-76页

作者： Qiuping Zhang Qiuju Huang Zhiping Cheng Wei Xue Shoushi Liu Yunnuo Liao Xiaolan Li Xin Chen Yaoyao Han Dan Zhu Zhiheng Su Xin Yang Zhuo Luo Hongwei Guo Department of Traditional Chinese medicine the First Affiliated Hospital of Guangxi Medical University Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation & College of Pharmacy Guangxi Medical University Key Laboratory of Longevity and aging-related Diseases of Chinese Ministry of Education & center for translational medicine Guangxi Medical University

Xiaoaiping(XAP) Injection demonstrates the anti-prostate cancer(PCa) effects, yet the underlying mechanism remains unclear. This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action. PCa cell proliferation was evaluated using a cell counting kit-8(CCK-8) assay. Cell apoptosis was assessed through Hoechst staining and Western blotting assays. Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells. To further validate potential key genes and important pathways, a series of assays were conducted, including acridine orange(AO)staining, transmission electron microscopy, and immunofluorescence assays. The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model. Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell *** C4-2 and prostate cancer cell line-3(PC3) cells, XAP induced cellular apoptosis, evidenced by reduced B-cell lymphoma 2(Bcl-2) levels and elevated Bcl-2-associated X(Bax) levels. Proteomic, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction(q RT-PCR) investigations revealed a strong correlation between forkhead box O3a(Fox O3a) autophagic degradation and the anti-PCa action of XAP. XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5(Atg5)/autophagy-related protein 12(Atg12) and enhancing Fox O3a expression and nuclear translocation. Furthermore,XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered Fox O3a nuclear translocation in tumor tissue. These findings suggest that XAP induces PCa apoptosis via inhibition of Fox O3a autophagic degradation, potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.

关键词： Apoptosis Autophagy Forkhead box O3a Prostate cancer Xiaoaiping Injection

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Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

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Neural Regeneration Research 2025年第1期20卷 93-106页

作者： Yujie Yang Xinyi Li Jiaying Lu Jingjie Ge Mingjia Chen Ruixin Yao Mei Tian Jian Wang Fengtao Liu Chuantao Zuo Key Laboratory of Arrhythmias Ministry of EducationDepartment of Medical GeneticsShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Department of Neurology National Research Center for Aging and MedicineNational Center for Neurological Disordersand State Key Laboratory of Medical NeurobiologyHuashan HospitalFudan UniversityShanghaiChina Department of Nuclear medicine&PET center National Center for Neurological Disordersand National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghaiChina International Human Phenome Institutes(Shanghai) ShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of *** review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest *** conducted a thorough literature search using reputable databases such as PubMed and Web of *** criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical *** findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting ***,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo *** validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic *** summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

关键词： aromatic amino acid decarboxylase brain imaging dopamine transporter Parkinson’s disease parkinsonism positron emission tomography presynaptic dopaminergic function vesicle monoamine transporter type 2

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Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert J.Thomas M.Brandon Westover Can Zhang Department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA center for translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA Division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and aging Research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

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Unraveling brain aging through the lens of oral microbiota

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Neural Regeneration Research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu Si Wang Weiqi Zhang Jing Qu Guang-Hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation center for Human Brain Protection and National Clinical Research center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina aging translational medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS Key Laboratory of Genomic and Precision medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina aging Biomarker Consortium BeijingChina State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing Institute for Stem Cell and Regenerative medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

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Immune cells:potential carriers or agents for drug delivery to the central nervous system

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Military Medical Research 2025年第1期12卷 121-153页

作者： Shan-Shan Zhang Ruo-Qi Li Zhong Chen Xiao-Ying Wang Aaron S.Dumont Xiang Fan School of Basic Medical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Key Laboratory of Neuropharmacology and translational medicine of Zhejiang Province Zhejiang Chinese Medical UniversityHangzhou 310053China Clinical Neuroscience Research center Department of Neurosurgery and NeurologyTulane University School of MedicineNew OrleansLA 70122USA

Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted ***,the access of nanoparticles/drugs to the central nervous system(CNS)remains a challenge mainly due to the obstruction from brain *** cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug ***,we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain *** subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS,as well as recent progress in rationally engineering immune cell-based DDS for CNS ***,we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.

关键词： Drug delivery systems Immune cells Blood-brain barrier Central nervous system

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BIBR1532 inhibits proliferation and metastasis of esophageal squamous cancer cells by inducing telomere dysregulation

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 214-225页

作者： Qin Wang Qing-Rong Li Lei Xu Zi-Chun Yuan Xiao Liu Mao-Ju Tang Man Luo Xiao-Wu Zhong Qiang Ma Xiao-Lan Guo Department of Clinical Laboratory Affiliated Hospital of North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina School of Laboratory medicine&translational medicine Research center North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a malignant tumor with high morbidity and mortality,and easy to develop resistance to chemotherapeutic *** are DNA-protein complexes located at the termini of chro-mosomes in eukaryotic cells,which are unreplaceable in maintaining the stability and integrity of ***,an RNA-dependent DNA polymerase,play vital role in telomere length maintain,targeting telomerase is a promising therapeutic strategy for ***150 and KYSE410 cells were cultured and exposed to various concentrations of *** viability was assessed at 48 hours and 72 hours to determine the IC50 *** effects of BIBR1532 on ESCC cell proliferation,migration,and cellular senescence were evaluated using the cell counting kit-8 assay,plate colony formation assay,scratch assay,transwell assay,andβ-galactosidase staining,*** blotting was performed to detect the expression of RESULTS The IC50 values for KYSE150 and KYSE410 cells after 48 hours of BIBR1532 exposure were 48.53μM and 39.59μM,*** values decreased to 37.22μM and 22.71μM,respectively,following a longer exposure of 72 ***1532 exhibited dose-dependent effects on KYSE150 and KYSE410 cells,including decreased hTERT expression,inhibition of proliferation and metastasis,and induction of cellular ***,BIBR1532 upregulated the expression of the DDR protein,γ-H2AX,and activated the ataxia telangiectasia and Rad3-related protein(ATR)/check point kinase 1(CHK-1)and ataxia-telangiectasia mutated gene(ATM)/CHK2 ***1532 downregulated the expression of telomere-binding proteins,including telomeric-repeat binding factor 1(TRF1),TRF2,protection of telomeres 1,and TIN2-interacting protein *** a nude mouse xenograft model,BIBR1532 significantly suppressed tumor growth,reduced hTERT expression,and increasedγ-H2AX protein *** and eosin staining of various organs,including the heart,liver,s

关键词： Esophageal squamous cell carcinoma BIBR1532 Human telomerase reverse transcriptase DNA damage response Telomere-binding proteins

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Both 20S and 19S proteasome components are essential for meiosis in male mice

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Zoological Research 2025年第01期 27-40页

作者： Ting-Ting Han Li-Ying Wang Qiu-Xing Zhou Wei Wei Yan-Jie Ma Ying-Hong Chen Wei Li Zhen-Yu Ju Chao Liu Key Laboratory of Regenerative medicine of Ministry of Education Institute of Aging and Regenerative Medicine Department of Developmental & Regenerative Medicine College of Life Science and Technology Jinan University Guangzhou Women and Children's Medical center Guangzhou Medical University

The proteasome, an evolutionarily conserved proteolytic complex comprising the 20S core particle and 19S regulatory particles, performs both shared and distinct ***, a highly complex developmental process, relies on proteasome activity at multiple stages to regulate protein turnover. In this study, we selected the20S subunit PSMA1 and 19S regulatory subunit PSMD2 to investigate the potential functions of the proteasome in spermatogenesis. Using Psma1-EGFP and Psmd2-mCherry knock-in mouse models, we confirmed the expression of both subunits in all spermatogenic cell types,with pronounced presence in early germ cell *** further clarify their functional significance, we specifically knocked out Psma1 and Psmd2 in germ *** of either PSMA1 or PSMD2 led to disrupted spermatogenesis, characterized by the complete absence of sperm in the epididymis. Subsequent analysis indicated that loss of these proteasome components impaired meiotic initiation. Psma1 and Psmd2 knockout germ cells showed accumulation of DMRT1, a key regulator of mitosis-to-meiosis transition, leading to a reduction in STRA8 levels and consequent disruption of meiosis initiation. This study sheds light on the molecular mechanisms that govern meiotic initiation and identifies potential genes associated with male infertility.

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Proteostasis failure:at the intersection between aging and Alzheimer's disease

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Neural Regeneration Research 2025年第11期20卷 3221-3222页

作者： Natalia Poblete Claudio Hetz center for Geroscience Brain Health and MetabolismSantiagoChile Biomedical Neuroscience Institute Faculty of MedicineUniversity of ChileSantiagoChile Program of Cellular and Molecular Biology Institute of Biomedical SciencesFaculty of MedicineUniversity of ChileSantiagoChile Buck Institute for Research on aging NovatoCAUSA

Lifestyle and demographics of the world's population are causing serious health problems impacting the brain,increasing the incidence of Alzheimer's disease(AD)and other types of *** we have gained important insights into the pathogenic mechanisms of AD,only palliative care is available to *** is characterized by the abnormal deposition of protein aggregates in the brain formed by amyloid β and hyper-phosphorylated,Tau in addition to neuroinflammation.

关键词： Alzheimer amyloid stasis

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Adenosine triphosphate-binding pocket inhibitor for mixed lineage kinase domain-like protein attenuated alcoholic liver disease via necroptosis-independent pathway

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World Journal of Gastroenterology 2025年第6期31卷 44-61页

作者： Han-Ning Xuan Yuan Hyun Sung Kim Gye Ryeol Park Jae Eun Ryu Ji Eun Kim In Young Kang Hye Young Kim Seung Min Lee Ju Hee Oh Eileen L Yoon Dae Won Jun Department of Internal medicine Hanyang University School of MedicineSeoul 04763South Korea Department of Pathology Hanyang University School of MedicineSeoul 04763South Korea Department of translational medicine Graduate School of Biomedical Science and EngineeringHanyang UniversitySeoul 04763South Korea Department of Obstetrics and Gynecology Institute of Women’s Medical Life ScienceYonsei Cancer CenterSeverance HospitalYonsei University College of MedicineSeoul 04763South Korea Department of Internal medicine Sanggye Paik HospitalInje University College of MedicineSeoul 01757South Korea

BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver *** study aims to specifically investigate the role of MLKL’s adenosine triphosphate(ATP)-binding pocket in facilitating necroptosis-independent pathways that may contribute to liver disease *** focusing on this mechanism,we seek to identify potential therapeutic targets that can modulate MLKL activity,offering new strategies for the prevention and treatment of liver-related *** To investigate the possibility of using the ATP-binding pocket-associated,necro-ptosis-independent MLKL pathway as a target for liver *** Cell death following necroptosis stimuli was evaluated using cell proliferation assays,flow cytometry,and electron microscopy in various *** human liver organoid system was used to evaluate whether the MLKL ATP pocket-binding inhibitor could attenuate ***,alcoholic and non-alcoholic fatty liver diseases animal models were used to determine whether MLKL ATP pocket inhibitors could attenuate liver *** While an MLKL ATP pocket-binding inhibitor did not prevent necroptosis-induced cell death in RAW 264.7 cells,it did reduce the necroptosis-led expression of CXCL2,ICAM,and ***,MLKL ATP pocket inhibitor diminishes the expression of CXCL2,ICAM,and VCAM by inhibiting the IκB kinase and nuclear factor kappa-B pathways without inducing necroptosis-induced cell death in two-dimensional cell culture as well as the human-derived liver organoid *** MLKL ATP-binding inhibitor was ineffective in non-alcoholic fatty liver disease animal models,MLKL ATP-binding inhibitor attenuated hepatic inflammation in the alcoholic liver disease *** MLKL ATP pocket-binding inhibitor exerted anti-inflammatory effects through the necroptosis-independent MLKL pathway in an animal model of alcoholic liver disease.

关键词： RAW 264.7 cell Cell death Necroptosis Mixed lineage kinase domain-like protein Non-alcoholic fatty liver disease Mixed lineage kinase domain-like protein adenosine triphosphate binding inhibitor Alcoholic liver disease

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Exploration of evolutionary mechanisms shaping KZFP and retrotransposon interactions

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Science Bulletin 2025年第3期70卷 328-332页

作者： Qian Wu Junqin Xu Jiaxin Zeng Yixuan Wang Peng Yang Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation Clinical Research Center for Anesthesiology and Perioperative MedicineTranslational Research Institute of Brain and Brain-Like IntelligenceShanghai Fourth People’s HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Institute for Regenerative medicine State Key Laboratory of Cardiology and Medical Innovation CenterShanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China

Retrotransposon expansion has profoundly reshaped genomes[1],[2].As crucial defense mechanisms that counteract retrotransposons in humans,members of the Krüppel-associated box(KRAB)zinc finger(ZF)protein(KZFP)family ... 详细信息

关键词： shaped expansion mechanisms

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