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Methylated CpG dinucleotides in the 5 -a reductase 2 gene may explain finasteride resistance in benign prostatic enlargement patients

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Asian Journal of Andrology 2021年第3期23卷 266-272页

作者： Zhe-Min Lin Dong-Dong Fan Song Jin Zhan-Liang Liu yi-nong niu Department of Urology Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100016China Department of Urology Beijing Miyun Teaching HospitalCapital Medical UniversityBeijing 101500China Department of Urology Beijing Tsinghua Changgung HospitalTsinghua UniversityBeijing 102218China

The inhibition of 5-a reductase type 2(SRD5A2)by finasteride is commonly used for the management of urinary obstruction resulting from benign prostatic enlargement(BPE).Certain BPE patients showing no SRD5A2 protein expression are resistant to finasteride *** previous work showed that methylated cytosine-phosphate-guanine(CpG)islands in the SRD5A2 gene might account for the absence or reduction of SRD5A2 protein ***,we found that the expression of the SRD5A2 protein was variable and that weak expression of the SRD5A2 protein(scored 0-100)occurred in 10.0%(4/40)of benign adult *** showed that the expression of SRD5A2 was negatively correlated with DNA methyltransferase 1(DNMT1)*** vitro SRD5A2-negative BPH-1 cells were resistant to finasteride treatment,and SRD5A2 was re-expressed in BPH-1 cells when SRD5A2 was demethylated by 5-Aza-2T-deoxycytidine(5-Aza-CdR)or N-phthalyl-L-tryptophan(RG108).Furthermore,we determined the exact methylation ratios of CpG dinucleotides in a CpG island of SRD5A2 through MassArray quantitative methylation *** methylated CpG dinucleotides,including four CpG dinucleotides in the promoter and six CpG dinucleotides in the first exon,were found in a CpG island located from-400 bp to+600 bp in SRD5A2,which might lead to the silencing of SRD5A2 and the absence or reduction of SRD5A2 protein *** cannot exert a therapeutic effect on patients lacking SRD5A2,which may partially account for the resistance to finasteride observed in certain BPE patients.

关键词： 5-a reductase benign prostatic enlargement CpG island methylated CpG dinucleotides methylation

The intriguing role of fibroblasts and c-Jun in the chemopreventive and therapeutic effect of finasteride on xenograft models of prostate cancer

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Asian Journal of Andrology 2016年第6期18卷 913-919页

作者： yi-nong niu Kai Wang Song Jin Dong-Dong Fan Ming-Shuai Wang Nian-Zeng Xing Shu-Jie Xia Department of Urology Beijing Chao-Yang Hospital Capital Medical University Beijing China Weifang Hospital of Traditional Chinese Medicine Weifang China Department of Urology Shanghai First Hospital Jiao Tong University Shanghai China

In a large clinical trial, finasteride reduced the rate of low-grade prostate cancer （PCa） while increasing the incidence of high-grade cancer. Whether finasteride promotes the development of high-grade tumors remains controversial. We demonstrated the role of fibroblasts and c-Jun in chemopreventive and therapeutic effect of finasteride on xenograft models of PCa. LNCaP （PC3） cells or recombinants of cancer cells and fibroblasts were implanted in male athymic nude mice treated with finasteride. Tumor growth, cell proliferation, apoptosis, p-Akt, and p-ERKI/2 were evaluated. In LNCaP （PC3） mono-grafted models, finasteride did not change the tumor growth. In recombinant-grafted models, fibroblasts and c-Jun promoted tumor growth; finasteride induced proliferation of LNCaP cells and repressed PC3 cell apoptosis. When c-Jun was knocked out, flbroblasts and/or finasteride did not promote the tumor growth. Finasteride inhibited p-Akt and p-ERKI/2 in mono-culture cancer cells while stimulating the same signaling molecules in the presence of fibroblasts. Reduced p-Akt and p-ERKI/2 were noted in the presence of c-Jun-I- fibroblasts. Fibroblasts and c-Jun promote PCa growth; finasteride further stimulates tumor growth with promoted proliferation, repressed apoptosis, and up-regulated pro-proliferative molecular pathway in the presence of fibroblasts and c-Jun. Stromal-epithelial interactions play critical roles in finasteride＇s therapeutic effects on PCa. Our findings have preliminary implications in using finasteride as a chemopreventive or therapeutic agent for PCa patients.

关键词： chemoprevention c-Jun fibroblasts finasteride mouse model prostate cancer

Differential expression of 5-alpha reductase sozymes in the prostate and its clinical implications

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Asian Journal of Andrology 2014年第2期16卷 274-279,I0010页

作者： Kai Wang Dong-Dong Fan Song Jin Nian-Zeng Xing yi-nong niu Department of Urology Beijing Chaoyang Hospital Capital Medical University Beijing China

The development of human benign or malignant prostatic diseases is closely associated with androgens, primarily testosterone （T） and dihydrotestosterone （DHT）. T is converted to DHT by 5-alpha reductase （5-AR） isozymes. Differential expression of 5-AR isozymes is observed in both human benign and malignant prostatic tissues. 5-AR inhibitors （5-ARI） are commonly used for the treatment of benign prostatic hyperplasia （BPH） and were once promoted as chemopreventive agents for prostate cancer （PCa）. This review discusses the role of the differential expression of 5-AR in the normal development of the human prostate and in the pathogenesis and progression of BPH and PCa.

关键词： 5-alpha reductase 5-alpha reductase inhibitor androgen benign prostatic hyperplasia prostate prostate cancer

Applications of in-situ solid-state nuclear magnetic resonance in methanol to olefins reaction

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Science China Chemistry 2025年第1期68卷 134-151页

作者： Jing niu Shutao Xu yingxu Wei Zhongmin Liu National Engineering Research Center of Lower-Carbon Catalysis Technology Dalian Institute of Chemical PhysicsChinese Academy of Sciences State Key Laboratory of Catalysis Dalian Institute of Chemical Physics Chinese Academy of Sciences University of Chinese Academy of Sciences

The methanol-to-olefins（MTO） reaction offers an alternative pathway for the production of low-carbon olefins from non-oil feedstocks. Fundamental research has been impeded by a lack of comprehensive understanding of its underlying mechanism,despite the significant progress made in industry. In-situ solid-state nuclear magnetic resonance（ss NMR） spectroscopy has emerged as a pivotal tool, offering crucial insights into key species under real-time operando conditions. Furthermore, the host–guest interaction between zeolites or surface species residing on zeolites and the reactant/active intermediates is revealed by the combination of in-situ13C MAS NMR and 2D correlation spectroscopy. Moreover, recent technological advancements in hyperpolarization（HP） methods, including HP129Xe NMR and dynamic nuclear polarization（DNP）, have significantly improved the sensitivity of ss NMR, enabling detailed structural and kinetic analysis as well as the detection of trace species. In this feature article, we summarized recent advancements in（in-situ） ss NMR spectroscopy applied to MTO reaction processes,encompassing mechanistic investigations at various stages and the intricate host–guest interactions. These theoretical insights into the dynamic evolution of MTO reactions lay a solid foundation for the optimization of catalytic processes and the development of efficient catalysts, thereby advancing the techniques towards more sustainable and economical production route for olefins.

关键词： MTO zeolites in-situ ssNMR reactive intermediates reaction mechanism

Ubiquitin-specific protease 1 facilitates tumor immune escape from natural killer cells and predicts the prognosis in small cell lung cancer

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Oncology Research 2025年第1期33卷 213-224页

作者： SHIQIN JIANG yiCHUN TANG FENG MA YUCHUN niu LEI SUN Department of Clinical Pharmacy Shenzhen Hospital of Integrated Traditional Chinese and Western MedicineShenzhen518104China Department of Pathology Zhujiang HospitalSouthern Medical UniversityGuangzhou510280China Department of Radiation Oncology The First People’s Hospital of FoshanFoshan528000China Department of Oncology The First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou510630China Department of Oncology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguan523721China

Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer *** substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limited to a minority of patients with *** the present study,novel indicators for predicting the outcomes and molecular targets for SCLC treatment were ***:We conducted bioinformatics analysis to identify the key genes associated with tumor-infiltrating lymphocytes in *** functional role of the key gene identified in SCLC was determined both in vitro and in ***:A significant correlation was observed between patient survival and CD56dim natural killer(NK)cell ***,we noted that the hub gene ubiquitin-specific protease 1(USP1)is closely correlated with both CD56dim NK cells and overall survival in *** analysis revealed that USP1 is upregulated in *** addition,gene set enrichment analysis revealed that USP1 overexpression hinders NK cell-mediated immune *** co-cultivating NK-92 cells with SCLC cells,we demonstrated that NK cell cytotoxicity against SCLC could be improved either via USP1 knock-down or pharmacological ***,using a nude-mice xenograft tumor model,we noted that USP1 inhibition effectively suppressed tumor proliferation and increased the expression of NK cell-associated ***:Our study findings highlight the importance of NK cells in regulating ***1 overexpression can inhibit NK cell-mediated immunity;therefore,USP1 may serve not only as a prognostic biomarker but also as a potential molecular target of SCLC therapy.

关键词： Ubiquitin-specific protease 1(USP1) Natural killer(NK)cell Small cell lung cancer(SCLC) Prognosis Immune escape

Weak KAM theory for two classes of almost periodic Hamiltonian systems

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Science China Mathematics 2025年

作者： Xun niu Kaizhi Wang Yong Li School of Mathematics and Statistics Center for Mathematics and Interdisciplinary SciencesNortheast Normal University School of Mathematical Sciences Shanghai Frontier Science Center of Modern Analysis (CMA-Shanghai)Shanghai Jiao Tong University Institute of Mathematics Jilin University

The purpose of this paper is to investigate the dynamics of Bohr almost periodic and Levitan almost periodic Hamiltonian systems via the weak KAM theory. We obtain minimal measures and weak KAM solutions in both cases. The weak KAM solution is a weak solution to the Hamilton-Jacobi equation, which formally transforms the original Hamiltonian systems into an integrable one. Consequently, we get the existence of an invariant torus in the aforementioned weak sense.

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C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury

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Neural Regeneration Research 2025年第8期20卷 2231-2244页

作者： Xiangzi Wang Xiaofei niu yingkai Wang Yang Liu Cheng Yang Xuyi Chen Zhongquan Qi School of Medicine Guangxi UniversityNanningGuangxi Zhuang Autonomous RegionChina Graduate School of Tianjin University of Traditional Chinese Medicine TianjinChina Characteristic Medical Center of People’s Armed Police Forces TianjinChina Fujian Maternity and Child Health Hospital FuzhouFujian ProvinceChina

Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory *** expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after *** studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for *** review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord ***,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 *** review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted ***,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 *** review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.

关键词： apoptosis C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway C-C motif chemokine receptor 2 antagonists chemokine ligand 2 chemokine receptor 2 inflammation macrophage microglia spinal cord injury therapeutic method

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Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders:drug stability,targeting efficiency,and safety

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Neural Regeneration Research 2025年第7期20卷 1883-1899页

作者： Mingyu Zhang Chunyu Xiang Renrui niu Xiaodong He Wenqi Luo Wanguo Liu Rui Gu Department of Orthopedic Surgery China-Japan Union Hospital of Jilin UniversityChangchunJilin ProvinceChina

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely ***,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic *** are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and ***,they can potentially treat traumatic and nontraumatic central nervous system *** this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics ***,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain *** studies related to liposomes are still in the laboratory stage and have not yet entered clinical ***,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and ***,we proposed development strategies related to liposomes to further promote their development in neurological disease research.

关键词： Alzheimer's disease amyotrophic lateral sclerosis brain tumors central nervous system Huntington's disease liposome drug delivery neurological disorders Parkinson's disease spinal cord injury traumatic brain injury

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Bidirectional regulation of the brain-gut-microbiota axis following traumatic brain injury

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Neural Regeneration Research 2025年第8期20卷 2153-2168页

作者： Xinyu You Lin niu Jiafeng Fu Shining Ge Jiangwei Shi Yanjun Zhang Pengwei Zhuang National Key Laboratory of Chinese Medicine Modernization Tianjin University of Traditional Chinese MedicineTianjinChina Haihe Laboratory of Modern Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjinChina First Teaching Hospital of Tianjin University of Traditional Chinese Medicine TianjinChina National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion TianjinChina

Traumatic brain injury is a prevalent disorder of the central nervous *** addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are *** dysfunction is a significant consequence of traumatic brain *** the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous *** gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated *** comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut ***,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain *** review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effec

关键词： traumatic brain injury brain-gut-microbiome axis gut microbiota neuroimmune immunosuppression host defense vagal afferents bacterial infection dorsal root ganglia nociception neural circuitry

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