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Discrimination of polysorbate 20 by high-performance liquid chromatography-charged aerosol detection and characterization for components by expanding compound database and library

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Journal of Pharmaceutical Analysis 2024年第5期14卷 722-732页

作者： Shi-Qi Wang Xun Zhao Li-Jun Zhang Yue-Mei Zhao Lei Chen Jin-Lin Zhang Bao-Cheng Wang Sheng Tang Tom Yuan Yaozuo Yuan Mei Zhang Hian Kee Lee Hai-Wei Shi Jiangsu Institute for Food and Drug Control Nanjing210019China School of pharmacy China Pharmaceutical UniversityNanjing211112China School of pharmacy Nanjing University of Chinese MedicineNanjing210046China Chinese Pharmacopoeia Commission Beijing100061China Nanjing Well Pharmaceutical Group Co. Ltd.Nanjing210018China School of Environmental and Chemical Engineering Jiangsu University of Science and TechnologyZhenjiangJiangsu212003China University of Massachusetts Amherst Amherst01003USA Department of Chemistry National University of SingaporeSingapore117543Singapore

Analyzing polysorbate 20(PS20)composition and the impact of each component on stability and safety is crucial due to formulation variations and individual *** similar structures and polarities of PS20 components make accurate separation,identification,and quantification *** this work,a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography(HPLC)with charged aerosol detection(CAD)to separate 18 key components with multiple *** separated components were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)with an identical gradient as the HPLC-CAD *** polysorbate compound database and library were expanded over 7-time compared to the commercial *** method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process ***-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different *** method observed the impact of 4 degradation conditions on peak components,identifying stable components and their tendencies to ***-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences,distinguishing quasi products.

关键词： Polysorbate 20 Component Database Discrimination Degradation

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Targeting ferroptosis and ferritinophagy:new targets for cardiovascular diseases

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 1-22页

作者： Yi LUAN Yang YANG Ying LUAN Hui LIU Han XING Jinyan PEI Hengdao LIU Bo QIN Kaidi REN Clinical Systems Biology Research Laboratories Translational Medicine Centerthe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China State Key Laboratory for Artificial Microstructures and Mesoscopic Physics School of PhysicsPeking UniversityBeijing100871China School of Laboratory Medicine Xinxiang Medical UniversityXinxiang453003China Quality Management Department Henan No.3 Provincial People’s HospitalZhengzhou450052China Department of Cardiology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Center for Translational Medicine the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Department of pharmacy the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Henan Key Laboratory of Precision Clinical pharmacy Zhengzhou UniversityZhengzhou450052China Henan Engineering Research Center for Application&Translation of Precision Clinical pharmacy Zhengzhou UniversityZhengzhou450052China

Cardiovascular diseases(CVDs)are a leading factor driving mortality ***,an essential trace mineral,is important in numerous biological processes,and its role in CVDs has raised broad discussion for ***-mediated cell death,namely ferroptosis,has attracted much attention due to its critical role in cardiomyocyte damage and ***,ferritinophagy is the upstream mechanism that induces ferroptosis,and is closely related to *** review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy,and the regulatory pathways and molecular targets involved in ferritinophagy,and to determine their roles in ***,we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating ***,this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.

关键词： Cardiovascular disease Iron Ferroptosis Ferritinophagy Therapeutic target

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Total glucosides of paeony alleviates cGAS-STING-mediated diseases by blocking the STING-IRF3 interaction

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Chinese Journal of Natural Medicines 2024年第5期22卷 402-415页

作者： XIU Ye WANG Sihao ZHANG Ping LI Chengwei WU Zhixin WEN Jincai XU Yingjie LV Guiji ZHAO Xiaomei DONG Xu CHEN Yichong LI Junjie WANG Yan ZOU Liang XIAO Xiaohe BAI Zhaofang School of pharmacy Fujian University of Traditional Chinese MedicineFuzhou 350122China Department of Hepatology The Fifth Medical Center of PLA General HospitalBeijing 100039China China Military Institute of Chinese Materia Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China Department of pharmacy Medical Supplies Center of PLA General HospitalBeijing 100039China School of Food and Biological Engineering Chengdu UniversityChengdu 610106China National Key Laboratory of Kidney Diseases Chinese PLA General HospitalBeijing 100039China

In the realm of autoimmune and inflammatory diseases,the cyclic GMP-AMP synthase(cGAS)stimulator of interferon genes(STING)signaling pathway has been thoroughly investigated and *** this,the clinical approval of drugs targeting the cGAS-STING pathway has been *** Total glucosides of paeony(TGP)is highly anti-inflammatory and is commonly used in the treatment of rheumatoid arthritis(RA),emerged as a subject of our *** found that the TGP markedly reduced the activation of the cGAS-STING signaling pathway,triggered by various cGAS-STING agonists,in mouse bone marrow-derived macrophages(BMDMs)and Tohoku Hospital Pediatrics-1(THP-1)*** inhibition was noted alongside the suppression of interferon regulatory factor 3(IRF3)phosphorylation and the expression of interferon-beta(IFN-β),C-X-C motif chemokine ligand 10(CXCL10),and inflammatory mediators such as tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6).The mechanism of action appeared to involve the TGP’s attenuation of the STING-IRF3 interaction,without affecting STING oligomerization,thereby inhibiting the activation of downstream signaling *** vivo,the TGP hindered the initiation of the cGAS-STING pathway by the STING agonist dimethylxanthenone-4-acetic acid(DMXAA)and exhibited promising therapeutic effects in a model of acute liver injury induced by lipopolysaccharide(LPS)and D-galactosamine(D-GalN).Our findings underscore the potential of the TGP as an effective inhibitor of the cGAS-STING pathway,offering a new treatment avenue for inflammatory and autoimmune diseases mediated by this pathway.

关键词： Total glucosides of gaeony cGAS-STING pathway Inflammation LPS/D-GalN STING inhibitor

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Mechanism of nanoparticle aggregation in gas-liquid microfluidic mixing

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Chinese Chemical Letters 2024年第4期35卷 376-381页

作者： Hongxia Li Xiyang Wang Du Qiao Jiahao Li Weiping Zhu Honglin Li Key Laboratory for Precision&Non-traditional Machining Technology of Ministry of Education Dalian University of TechnologyDalian 116023China Shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science and TechnologyShanghai 200237China

Using gas-liquid segmented micromixers to prepare nanoparticles that have a homogeneous particle size, controllable shape, and monodispersity advantages. Although nanoparticle aggregation within a microfluid has been shown to be affected by the shear effect, the shear effect triggering conditions in gasliquid two-phase flow is unclear and the aggregation behavior of nanoparticles under the shear effect is difficult to predict, resulting in uncontrollable physical and chemical properties of nanoparticle aggregates. In this study, a numerical simulation of nanoparticle aggregation in gas-liquid two-phase flow under the shear effect is performed using the CFD-DEM method. Then, the effects of total flow rate,gas-liquid two-phase flow ratio, and particle volume fraction on particle aggregation were analyzed to achieve control of particle aggregation shape and size. Meanwhile, the triggering mechanism of the shear effect and the mechanism of the shear effect on the aggregation of nanoparticles were clarified. The results show that increasing the total flow rate or decreasing the gas-liquid two-phase flow rate ratio can induce the shear effect, which reduces the particle aggregation size and makes the morphology tend to be spherical. Moreover, increasing the particle volume fraction, and total flow rate or decreasing the gas-liquid two-phase flow rate ratio also increases the number of particle collisions and induce interparticle adhesion. Hence, particle adhesion and the shear effect compete with each other and together affect particle aggregation.

关键词： Microfluidic Gas-liquid segmented micromixer Nanoparticle aggregation Shear effect Numerical calculation

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A naturally derived small molecule compound suppresses tumor growth and metastasis in mice by relieving p53-dependent repression of CDK2/Rb signaling and the Snail-driven EMT

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Chinese Journal of Natural Medicines 2024年第2期22卷 112-126页

作者： REN Boxue LI Yang DI Lei CHENG Ranran LIU Lijuan LI Hongmei LI Yi TANG Zhangrui YAN Yongming LU Tao FU Rong CHENG Yongxian WU Zhaoqiu State Key Laboratory of Natural Medicines Department of PharmacologySchool of PharmacyChina Pharmaceutical UniversityNanjing 211198China Institute for Inheritance-Based Innovation of Chinese Medicine School of Pharmaceutical SciencesShenzhen University Health Science CenterShenzhen 518060China

The tumor suppressor protein p53 is central to cancer biology,with its pathway reactivation emerging as a promising therapeutic strategy in *** study introduced LZ22,a novel compound that selectively inhibits the growth,migration,and metastasis of tumor cells expressing wild-type p53,demonstrating ineffectiveness in cells devoid of p53 or those expressing mutant ***22’s mechanism of action involves a high-affinity interaction with the histidine-96 pocket of the MDM2 *** interaction disrupted the MDM2-p53 binding,consequently stabilizing p53 by shielding it from proteasomal ***22 impeded cell cycle progression and diminished cell proliferation by reinstating the p53-dependent suppression of the CDK2/Rb signaling ***,LZ22 alleviated the p53-dependent repression of Snail transcription factor expression and its consequent EMT,effectively reducing tumor cell migration and distal ***,LZ22 administration in tumor-bearing mice did not manifest notable side *** findings position LZ22 as a structurally unique reactivator of p53,offering therapeutic promise for the management of human cancers with wild-type TP53.

关键词： LZ22 Wild-type p53 p53 Reactivator Snail-driven EMT Tumor growth and metastasis

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Traditional Chinese Medicine Integrated Responsive Microneedles for Systemic Sclerosis Treatment

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Research 2024年第1期2023卷 139-147页

作者： Xi Luan Xiaoxuan Zhang Min Nie Yuanjin Zhao Department of Rheumatology and Immunology Nanjing Drum Tower HospitalSchool of PharmacyClinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing 210023China State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China

Traditional Chinese medicine,such as Tripterygium wilfordii and Paeonia lactiflora,has potential values in treating systemic sclerosis(SSc)and other autoimmune diseases,while their toxic side effect elimination and precise tropical drug delivery are still ***,we present multiple traditional Chinese medicine integrated photoresponsive black phosphorus(BP)microneedles(MNs)with the desired features for the SSc *** employing a template-assisted layer-by-layer curing method,such MNs with triptolide(TP)/paeoniflorin(Pae)needle tips and BP-hydrogel needle bottoms could be well *** combined administration of TP and Pae can not only provide anti-inflammatory,detoxification,and immunomodulatory effects to treat skin lesions in the early stage of SSc but also remarkably reduce the toxicity of single drug ***,the additive BPs possess good biocompatibility and near-infrared(NIR)responsiveness,imparting the MN photothermal-controlled drug release *** on these features,we have demonstrated that the traditional Chinese medicine integrated responsive MNs could effectively improve skin fibrosis and telangiectasia,reduce collagen deposition,and reduce epidermal thickness in the SSc mouse *** results indicated that the proposed Chinese medicine integrated responsive MNs had enormous potential in clinical therapy of SSc and other diseases.

关键词： needle precise template

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STING signaling in islet macrophages impairs insulin secretion in obesity

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Science China(Life Sciences) 2024年第2期67卷 345-359页

作者： Ze Hong Saihua Chen Jing Sun Dan Cheng Hanli Guo Jiahao Mei Xiang Zhang Munire Maimaiti Haiping Hao Peng Cao Haiyang Hu Chen Wang School of pharmacy Nanjing University of Chinese MedicineNanjing 210023China State Key Laboratory of Natural Medicines Department of Life Science and TechnologyChina Pharmaceutical UniversityNanjing 211198China School of Life Sciences Westlake UniversityHangzhou 310012China

The innate immune regulator stimulator of interferon genes(STING)mediates self-DNA sensing and leads to the induction of type I interferons and inflammatory cytokines,which promotes the progression of various inflammatory and autoimmune *** immune system plays a critical role in regulating obesity-induced islet dysfunction,whereas the potential effect of STING signaling is not fully ***,we demonstrate that STING is mainly expressed and activated in islet macrophages upon high-fat diet(HFD)***^(-/-)alleviates HFD-induced islet inflammation by inhibiting the expression of pro-inflammatory cytokines and the infiltration of ***,palmitic acid incubation promotes mitochondrial DNA leakage into the cytosol and subsequently activates STING pathway in ***,STING activation in macrophages impairs glucose-stimulated insulin secretion by mediating the engulfment ofβcell insulin secretory *** inhibiting STING activation enhances insulin secretion to control ***,our results reveal a regulatory mechanism in controlling the islet inflammation and insulin secretion in dietinduced obesity and suggest that selective blocking of the STING activation may be a promising strategy for treating type 2 diabetes.

关键词： STING obesity type 2 diabetes insulin macrophages islet

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Cognitive impairment in cerebral small vessel disease induced by hypertension

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Neural Regeneration Research 2024年第7期19卷 1454-1462页

作者： Weipeng Wei Denglei Ma Lin Li Lan Zhang Department of pharmacy Xuanwu Hospital of Capital Medical UniversityBeijingChina Beijing Geriatric Medical Research Center Beijing Engineering Research Center for Nervous System DrugsNational Center for Neurological DisordersNational Clinical Research Center for Geriatric DiseasesBeijingChina

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular *** r,the causal relationship between hypertension and cerebral small vessel disease remains *** has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular *** hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and *** is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of *** review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive *** also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

关键词： blood-brain barrier cerebral small vessel disease cognitive impairment dementia endothelial dysfunction enlarged perivascular space hypertension lacunar infarction neuroinflammation treatment white matter high signal intensity

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Traditional Chinese medicine for the treatment of immune-related nephropathy:A review

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Acta Pharmaceutica Sinica B 2024年第1期14卷 38-66页

作者： Pu Jiang Changliang Yao De-an Guo School of pharmacy Nanjing University of Chinese MedicineNanjing 210023China Shanghai Research Center for Modernization of Traditional Chinese Medicine National Engineering Research Center of TCM Standardization TechnologyShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China

Immune-related nephropathy(IRN)refers to immune-response-mediated glomerulonephritis and is the main cause of end-stage renal *** pathogenesis of IRN is not fully understood;therefore,treatment is *** Chinese medicines(TCMs)have potent clinical effects in the treatment of the IRN conditions immunoglobulin A nephropathy,lupus nephropathy,and diabetic *** underlying mechanisms mainly include its inhibition of inflammation;improvements to renal interstitial fibrosis,oxidative stress,autophagy,apoptosis;and regulation of *** this review,we summarize the clinical symptoms of the three IRN subtypes and the use of TCM prescriptions,herbs,and bioactive compounds in treating IRN,as well as the potential mechanisms,intending to provide a reference for the future study of TCM as IRN treatments.

关键词： IgA nephropathy Diabetic nephropathy Lupus nephritis Traditional Chinese medicine Immunity Pathogenesis Mechanism Pathophysiology

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Ten ring-B aromatized ergosterols from Aspergillus spectabilis

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Chinese Journal of Natural Medicines 2024年第7期22卷 654-662页

作者： WEI Mengsha SUN Weiguang LIU Linlin LI Yongqi LI Lanqin LI Qin CHEN Yu GUO Jieru GU Lianghu ZHU Hucheng CHEN Chunmei ZHANG Yonghui Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation School of PharmacyTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Tongji Hospital Affiliated to Tongji Medical College Huazhong University of Science and TechnologyWuhan 430030China

Spectasterols F−O(1−10),ten interesting ergosterols with an aromatized B ring,were obtained from Aspergillus *** structures and absolute configurations were determined using a combination of high-resolution electrospray ionization mass spectrometry(HR-ESI-MS),nuclear magnetic resonance(NMR)spectroscopy,single-crystal X-ray diffraction analyses,and electronic circular dichroism(ECD)***,these aromatic ergosterols feature versatile side ***,compound aromatic ergosterols featured versatile side chains,and compound 4 is an unusual C23 ergosterol characterized by a shorter side chain due to oxidative cleavage between C-23 and *** compounds were evaluated for their neuroprotective activities,with compound 8 showing a dose-dependent ability to reduce apoptosis and protect mitochondrial function in glutamate-induced SH-SY5Y cells.

关键词： Steroids Aspergillus spectabilis Aromatic ergosterols Neuroprotective activities Structure elucidation

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