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Salsolinol as an RNA m~6A methylation inducer mediates dopaminergic neuronal death by regulating YAP1 and autophagy

Neural Regeneration Research 2025年第3期20卷 887-899页

作者： Jianan Wang Yuanyuan Ran Zihan Li Tianyuan Zhao Fangfang Zhang Juan Wang Zongjian Liu Xuechai Chen beijing International Science and Technology Cooperation Base for Antiviral drugs College of Chemistry and LifeBeijing University of TechnologyBeijingChina Department of Rehabilitation Beijing Rehabilitation HospitalCapital Medical UniversityBeijingChina

Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environmental toxin that causes Parkinson's ***,the mechanism by which Sal mediates dopaminergic neuronal death remains *** this study,we found that Sal significantly enhanced the global level of N~6-methyladenosine(m~6A)RNA methylation in PC12 cells,mainly by inducing the downregulation of the expression of m~6A demethylases fat mass and obesity-associated protein(FTO)and alk B homolog 5(ALKBH5).RNA sequencing analysis showed that Sal downregulated the Hippo signaling *** m~6A reader YTH domain-containing family protein 2(YTHDF2)promoted the degradation of m~6A-containing Yes-associated protein 1(YAP1)mRNA,which is a downstream key effector in the Hippo signaling ***,downregulation of YAP1 promoted autophagy,indicating that the mutual regulation between YAP1 and autophagy can lead to *** findings reveal the role of Sal on m~6A RNA methylation and suggest that Sal may act as an RNA methylation inducer mediating dopaminergic neuronal death through YAP1 and *** results provide greater insights into the neurotoxic effects of catechol isoquinolines compared with other studies and may be a reference for assessing the involvement of RNA methylation in the pathogenesis of Parkinson's disease.

关键词： ALKBH5 autophagy FTO Hippo pathway m~6A Parkinson's disease RNA methylation salsolinol YAP1 YTHDF2

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Development of a new ferulic acid certified reference material for use in clinical chemistry and pharmaceutical analysis

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Acta Pharmaceutica Sinica B 2015年第3期5卷 231-237页

作者： Dezhi Yang Fengfeng Wang Li Zhang Ningbo Gong Yang Lv beijing key laboratory of polymorphic drugs Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College

This study compares the results of three certified methods, namely differential scanning calorimetry (DSC), the mass balance (MB) method and coulometric titrimetry (CT), in the purity assessment of ferulic acid certified reference material (CRM). Purity and expanded uncertainty as determined by the three methods were respectively 99.81%, 0.16%; 99.797, 0.16%; and 99.81%, 0.26% with, in all cases, a coverage factor (k) of 2 (P=95%). The purity results are consistent indicating that the combination of DSC, the MB method and CT provides a confident assessment of the purity of suitable CRMs like ferulic acid. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

关键词： Differential scanning calorimetry Mass blance Coulometric titrimetry Certified reference material Uncertainty ferulic acid

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Nanoparticles for the treatment of spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1665-1680页

作者： Qiwei Yang Di Lu Jiuping Wu Fuming Liang Huayi Wang Junjie Yang Ganggang Zhang Chen Wang Yanlian Yang Ling Zhu Xinzhi Sun Department of Orthopedic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina CAS key laboratory of Standardization and Measurement for Nanotechnology CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijingChina University of Chinese Academy of Sciences BeijingChina Department of Neurosurgery The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.

关键词： antioxidants axon regeneration biocompatible materials drug carriers nanoparticles nerve regeneration neuroinflammatory diseases neuroprotection spinal cord injury stem cells

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Study on four polymorphs of bifendate based on X-ray crystallography

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Acta Pharmaceutica Sinica B 2016年第3期6卷 234-242页

作者： Jinju Nie Dezhi Yang Kun Hu Yang Lu beijing City key laboratory of polymorphic drugs Center of Pharmaceutical Polymorphs Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College

Bifendate, a synthetic anti-hepatitis drug, exhibits polycrystalline mode phenomena with 2polymorphs reported(forms A and B). Single crystals of the known crystalline form B and 3 new crystallosolvates involving bifendate solvated with tetrahydrofuran(C), dioxane(D), and pyridine(E) in a stoichiometric ratio of 1:1 were obtained and characterized by X-ray crystallography, thermal analysis,and Fourier transform infrared(FT-IR) spectroscopy. The differences in molecular conformation,intermolecular interaction and crystal packing arrangement for the four polymorphs were determined and the basis for the polymorphisms was investigated. The rotation of single bonds resulted in different orientations for the biphenyl, methyl ester and methoxyl groups. All guest solvent molecules interacted with the host molecule via an interesting intercalative mode along the [1 0 0] direction in the channel formed by the host molecules through weak aromatic stacking interactions or non-classical hydrogen bonds, of which the volume and planarity played an important role in the intercalation of the host with the guest. The incorporation of solvent-augmented rotation of the C–C bond of the biphenyl group had a striking effect on the host molecular conformation and contributed to the formation of bifendate polymorphs. Moreover, the simulated powder X-ray diffraction(PXRD) patterns for each form were calculated on the basis of the single-crystal data and proved to be unique. The single-crystal structures of the four crystalline forms are reported in this paper.

关键词： Bifendate Polymorphism Solvatomorphism Single-crystal structure Thermal analysis FT-IR

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Protein nanoparticles as potent delivery vehicles for polycytosine RNA-binding protein one

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World Journal of Diabetes 2025年第1期16卷 222-225页

作者： Zi-Yu Zhao Pei-Li Luo Xia Guo Zheng-Wei Huang State key laboratory of Bioactive Molecules and Druggability Assessment Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative DrugsCollege of PharmacyJinan UniversityGuangzhou 511436Guangdong ProvinceChina

Ma et al recently reported in the World Journal of Diabetes that ferroptosis occurs in osteoblasts under high glucose conditions,reflecting diabetes *** condition could be protected by the upregulation of the gene encoding polycytosine RNA-binding protein 1(PCBP1).Additionally,Ma et al used a lentivirus infection system to express *** the authors’method of administration can be improved in terms of stability and cost,we propose delivering PCBP1 to treat type 2 diabetic osteoporosis by encapsulating it in protein ***,PCBP1 is small and ***,intravenous injection can help deliver PCBP1 across the mucosa while avoiding acid and enzyme-catalyzed ***,incorporating PCBP1 into nanoparticles prevents its interaction with water or oxygen and protects PCBP1’s structure and ***,the safety of the protein materials and the industrialization techniques for large-scale production of protein nanoparticles must be comprehensively investigated before clinical application.

关键词： Polycytosine RNA-binding protein 1 Protein nanoparticle Osteoblast Ferroptosis Diabetes

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A series of stable, metastable and unstable salts of Imatinib with improved solubility

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Chinese Chemical Letters 2022年第4期33卷 2159-2164页

作者： Zheng-Yu Fang Bao-Xi Zhang Wen-Hui Xing Hong-Li Jia Xue Wang Ning-Bo Gong Yang Lu Guan-Hua Du beijing key laboratory of polymorphic drugs Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China State key laboratory of Natural and Biomimetic drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191 China beijing City key laboratory of Drug Target Identification and Drug Screening Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Pharmaceutical salt formation is the most preferred and effective method to enhance the physicochemical properties of APIs. The aim of the study was to design and synthesize a series of new salts to improve the solubility of Imatinib(IM). Two stable salts with malonic acid(S1) and citric acid(S5), one metastable salt with fumaric acid(S2), two unstable salts with citric acid(S3, S4) were obtained for the first *** crystal and powder X-ray diffraction, Fourier transform infrared, differential scanning calorimetry,and thermogravimetric analysis were used to characterize the novel salts. The solubility and stability of the solid were also evaluated, and three salts(S1, S2, S5) had a more than 20 folds of solubility and a faster dissolution rate improved as compared to the pure drug in water and p H 6.8 buffer, respectively.

关键词： Imatinib Salt Characterization Stability Solubility

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Progress of research in the application of ultrasound technology for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2823-2837页

作者： Qiuquan Cai Lianghui Meng Meina Quan Ling Wang Jing Ren Chenguang Zheng Jiajia Yang Dong Ming Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina Innovation Center for Neurological Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Brain-Computer Interaction and Human-Machine Fusion Haihe laboratory Tianjin UniversityTianjinChina Tianjin key laboratory of Brain Science and Neural Engineering Tianjin UniversityTianjinChina

Alzheimer’s disease is a common neurodegenerative disorder defined by decreased reasoning abilities,memory loss,and cognitive *** presence of the blood-brain barrier presents a major obstacle to the development of effective drug therapies for Alzheimer’s *** use of ultrasound as a novel physical modulation approach has garnered widespread attention in recent *** a safe and feasible therapeutic and drug-delivery method,ultrasound has shown promise in improving cognitive *** article provides a summary of the application of ultrasound technology for treating Alzheimer’s disease over the past 5 years,including standalone ultrasound treatment,ultrasound combined with microbubbles or drug therapy,and magnetic resonance imaging-guided focused ultrasound *** is placed on the benefits of introducing these treatment methods and their potential *** found that several ultrasound methods can open the blood-brain barrier and effectively alleviate amyloid-βplaque *** believe that ultrasound is an effective therapy for Alzheimer’s disease,and this review provides a theoretical basis for future ultrasound treatment methods.

关键词： Alzheimer’s disease blood-brain barrier drugs magnetic resonance imaging-guided focused ultrasound microbubbles scanning ultrasound ultrasound ultrasound stimulation

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The Chinese patent medicine, Jin-tang-ning, ameliorates hyperglycemia through improving β cell function in pre-diabetic KKAy mice

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Chinese Journal of Natural Medicines 2020年第11期18卷 827-836页

作者： LIU Shuai-Nan LIU Quan LEI Lei SUN Su-Juan LI Cai-Na HUAN Yi HOU Shao-Cong SHEN Zhu-Fang State key laboratory of Bioactive Substances and Functions of Natural Medicines Key laboratory of Polymorphic Drugs of BejingInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBejing 100050China

Jin-tang-ning(JTN), a Chinese patent medicine, mainly comprised of Bombyx mori L., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes(T2 DM). Recently, we have reported that JTN could ameliorate postprandial hyperglycemia and improved β cell function in monosodium glutamate(MSG)-induced obese mice,suggesting that JTN might play a potential role in preventing the conversion of impaired glucose tolerance(IGT) to T2 DM. In this study, we evaluated the effect of JTN on the progression of T2 DM in the pre-diabetic KKAy mice. During the 10 weeks of treatment,blood biochemical analysis and oral glucose tolerance tests were performed to evaluate glucose and lipid profiles. The β cell function was quantified using hyperglycemic clamp at the end of the study. JTN-treated groups exhibited slowly raised fasting and postprandial blood glucose levels, and also ameliorated lipid profile. JTN improved glucose intolerance after 8 weeks of treatment. Meanwhile, JTN restored glucose-stimulated first-phase of insulin secretion and induced higher maximum insulin levels in the hyperglycemic ***, to investigate the underlying mechanisms of JTN in protecting β cell function, the morphologic changes of the pancreatic islets were observed by optical microscope and immunofluorescence of hormones(insulin and glucagon). Pancreatic protein expression levels of key factors involving in insulin secretion-related pathway and ER stress were also detected by Western blot. Pre-diabetic KKAy mice exhibited a compensatory augment in β cell mass and abnormal α cell distribution. Long-term treatment of JTN recovered islet morphology accompanied by reducing α cell area in KKAy mice. JTN upregulated expression levels of glucokinase(GCK), pyruvate carboxylase(PCB) and pancreas duodenum homeobox-1(PDX-1), while down-regulating C/EBP homologous protein(Chop)expression in pancreas of the hyperglycemic clamp, which indicated the improvem

关键词： Jin-tang-ning(JTN) Pre-diabetes βCell function Type 2 diabetes ER stress

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Theoretical and experimental cocrystal screening of temozolomide with a series of phenolic acids, promising cocrystal coformers

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Chinese Chemical Letters 2024年第5期35卷 407-417页

作者： Hongmei Yu Baoxi Zhang Meiju Liu Cheng Xing Guorong He Li Zhang Ningbo Gong Yang Lu Guanhua Du beijing key laboratory of polymorphic drugs Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China beijing City key laboratory of Drug Target Identification and Drug Screening Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

The virtual cocrystal screening approach based on molecular electrostatic potential surface(MEPS)maps is a fast and feasible computational method to estimate the probability of cocrystal formation by calculating the difference in the interaction site pairing energies of monomers and that of their assemblies prior to experimental *** this paper,we report 12 cocrystal forms of temozolomide with mono-,di-,and trihydroxy benzoic acids,namely,3-hydroxy-,2,4-dihydroxy-,2,5-dihydroxy-,2,6-dihydroxy-,3,4-dihydroxy-,and 3,4,5-trihydroxy-benzoic acids,as well as benzoic acid,as pharmaceutical coformers for the first time.10 single crystals out of the 12 cocrystal forms were obtained and unequivocally determined by single-crystal X-ray diffraction,which clarified spatial arrangements,molecular conformations,and supramolecular *** further gains some insights into the sites of hydrogen bonding interactions for exploring combination patterns in these *** stability of TMZ was successfully achieved by cocrystallization with these acids.

关键词： Virtual Cocrystal Temozolomide Supramolecular synthon Phenolic acid Stability

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Activation of Nrf2 attenuates pulmonary vascular remodeling via inhibiting endothelial-to-mesenchymal transition

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中国药理学与毒理学杂志 2018年第4期32卷 275-276页

作者： Yu-cai CHEN Tian-yi YUAN Di CHEN Lian-hua FANG Yang LYU Guan-hua DU beijing key laboratory of Drug Targets Identification and Drug Screening beijing key laboratory of polymorphic drugs Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China

OBJECTIVE To investigate the pharmacological effect and mechanism of Salvianolic acid A(SAA) on pulmonary vascular *** In current study,we conducted a series of experiments to clarify the effect of SAA,a kind of polyphenol compound,in the process of EndMT in human pulmonary arterial endothelial cells and in vivo therapeutic efficacy on vascular remodeling in monocrotaline(MCT)-induced *** was also induced by TGF-β1 in human pulmonary arterial endothelial cells(HPAECs) in *** SAA significantly attenuated EndMT,*** inhibited cell migration and reactive oxygen species(ROS) *** MCT-induced pulmonary arterial hypertension(PAH) model,SAA improved vascular function,decreased TGF-β1 level and *** ***,SAA stimulated Nrf2 translocation and subsequent heme ***-1(HO-1) *** effect of SAA on EndMT in vitro was abolished by ZnPP,a HO-1 *** This study indicates a deleterious impact of oxidative stress on *** antioxidant treatment may provide an adjunctive action to alleviate pulmonary vascular remodeling via inhibiting EndMT.

关键词：丹酚酸肺血管药理作用药物分析

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