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Isoimperatorin alleviates acetic acid-induced colitis in rats

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Asian Pacific Journal of Tropical Biomedicine 2024年第4期14卷 147-153页

作者： Saied Goodarzi Amir Hossein Abdolghaffari Behnaz Najafi Mostafa Pirali Hamedani Saeed Tavakoli Mahshad Marvi Maryam Baeeri Narguess Yassa Abbas Hadjiakhoondi Mohammad Abdollahi Zahra Tofighi Medicinal Plants Research Center Faculty of PharmacyTehran University of Medical SciencesTehranIran Department of Toxicology and pharmacology Faculty of PharmacyTehran Medical SciencesIslamic Azad UniversityTehranIran Department of Pharmacognosy Faculty of PharmacyTehran University of Medical SciencesTehranIran Medicinal Plants Research Center Institute of Medicinal PlantsACECRKarajIran International Campus School of pharmacy Tehran University of Medical SciencesTehranIran Toxicology and Diseases group The Pharmaceutical Sciences Research CenterTehran University of Medical SciencesTehranIran Department of Toxicology and pharmacology Faculty of PharmacyTehran University of Medical SciencesTehranIran

Objective:To investigate the effect of isoimperatorin on histopathological and biochemical changes in acetic acid-induced colitis ***:Colitis was induced by intracolonic administration of acetic acid solution(4%v/v)in *** were divided into six groups including the sham group,the negative control group,the dexamethasone-treated group,and the groups treated with isoimperatorin(0.1,1,and 10 mg/kg/d by gavage).The treatments were administered for three days and then colonic status was assessed by macroscopic,histopathological,and biochemical ***:Isoimperatorin significantly alleviated colonic damage in a dose-dependent manner and improved histological changes in rats with acetic acid-induced *** also significantly reduced myeloperoxidase,TNF-α,IL-1β,and malodialdehyde ***:Isoimperatorin alleviates acetic acid-induced colitis in rats and may be a potential therapeutic agent for the treatment of colitis.

关键词： Isoimperatorin Inflammatory bowel disease Acetic acid Colitis TNF-α IL-1β

Biomaterials-based anti-inflammatory treatment strategies for Alzheimer's disease

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Neural Regeneration Research 2024年第1期19卷 100-115页

作者： Jianjian Chu Weicong Zhang Yan Liu Baofeng Gong Wenbo Ji Tong Yin Chao Gao Danqi Liangwen Mengqi Hao Cuimin Chen Jianhua Zhuang Jie Gao You Yin Department of Neurology Second Affiliated Hospital(Shanghai Changzheng Hospital)of Naval Medical UniversityShanghaiChina School of pharmacy University College LondonLondonUK Department of clinical pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineClinical Pharmacy Innovation InstituteShanghai Jiao Tong University School of MedicineShanghaiChina School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghaiChina Changhai clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghaiChina

The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease *** re,there is an urgent need for new effective *** underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease *** inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's *** review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's *** review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.

关键词： Alzheimer's disease anti-inflammation blood-brain barrier drug delivery microglia nanoparticles neuroinflammation plant extracts

Synergistic chemotherapy/PTT/oxygen enrichment by multifunctional liposomal polydopamine nanoparticles for rheumatoid arthritis treatment

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 86-102页

作者： Xiaoling Fu Yutong Song Xianquan Feng Zhihong Liu Wenhao Gao Hongtao Song Qian Zhang School of pharmacy Fujian Medical UniversityFuzhou 350108China Fuzong clinical Medical College of Fujian Medical University Fuzhou 350025China First school of clinical medicine Nanjing Medical UniversityNanjing 211166China

Amultifunctional liposomal polydopamine nanoparticle(MPM@Lipo)was designed in this study,to combine chemotherapy,photothermal therapy(PTT)and oxygen enrichment to clear hyperproliferating inflammatory cells and improve the hypoxic microenvironment for rheumatoid arthritis(RA)***@Lipo significantly scavenged intracellular reactive oxygen species and relieved joint hypoxia,thus contributing to the repolarization of M1 macrophages into M2 ***,MPM@Lipo could accumulate at inflammatory joints,inhibit the production of inflammatory factors,and protect cartilage in vivo,effectively alleviating RA progression in a rat adjuvant-induced arthritis ***,upon laser irradiation,MPM@Lipo can elevate the temperature to not only significantly obliterate excessively proliferating inflammatory cells but also accelerate the production of methotrexate and oxygen,resulting in excellent RA treatment ***,the use of synergistic chemotherapy/PTT/oxygen enrichment therapy to treat RA is a powerful potential strategy.

关键词： Polydopamine Thermosensitive liposomes Photothermal therapy Oxygen generation Rheumatoid arthritis

Understanding the Novel Approach of Nanoferroptosis for Cancer Therapy

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Nano-Micro Letters 2024年第9期16卷 501-556页

作者： Afsana Sheikh Prashant Kesharwani Waleed H.Almalki Salem Salman Almujri Linxin Dai Zhe‑Sheng Chen Amirhossein Sahebkar Fei Gao Department of Pharmaceutics School of Pharmaceutical Education and ResearchJamia HamdardNew Delhi 110062India Department of pharmacology and Toxicology Faculty of PharmacyUmm Al-Qura UniversityMakkahSaudi Arabia Department of pharmacology College of PharmacyKing Khalid University61421 Asir‑AbhaSaudi Arabia State Key Laboratory of Southwestern Chinese Medicine Resources Pharmacy SchoolChengdu University of Traditional Chinese MedicineChengdu 611130People’s Republic of China Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityNew York 11439USA Biotechnology Research Center Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran Applied Biomedical Research Center Mashhad University of Medical SciencesMashhadIran

As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer *** molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of *** to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active *** review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and ***,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.

关键词： Ferroptosis Nanoparticles Ferrotherapy Cancer Genes Nanotechnology Toxicity Reactive oxygen species

Ascophyllum nodosum and Fucus vesiculosus ameliorate restenosis via improving inflammation and regulating the PTEN/PI3K/AKT signaling pathway

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Food Science and Human Wellness 2024年第3期13卷 1711-1728页

作者： Crystal Ngofi Zumbi Chun-Hsu Pan Hui-Yu Huang Chieh-Hsi Wu Program in clinical Drug Development from Herbal Medicine College of PharmacyTaipei Medical UniversityTaipei 11031China Program in Drug Discovery and Development Industry College of PharmacyTaipei Medical UniversityTaipei 11031China School of pharmacy Taipei Medical UniversityTaipei 11031China Graduate Institute of Metabolism and Obesity Sciences Taipei Medical UniversityTaipei 11031China

Restenosis is a common complication following coronary *** traditional use of seaweeds for health benefits has increasingly been explored,however few studies exist reporting its protective effects on the development of restenosis and gut *** aim of this study was to investigate the potential of seaweed extracts(SE) of Ascophyllum nodosum and Fucus vesiculosus in inhibiting intimal hyperplasia in a rat model of restenosis and its underlying mechanisms in macrophages and vascular smooth muscle cells(vSMCs).16S rRNA sequencing was done to investigate the regulatory effect of SE on the gut microbiome of injured *** indicated by the results,SE significantly inhibited the progression of intimal hyperplasia in vivo,attenuated inflammation in macrophages and could inhibit the proliferation,dedifferentiation and migration of *** was observed through immunoblotting assays that treatment with SE significantly upregulated PTEN expression in macrophages and inhibited the upregulation of PI3K and AKT expression in ***,according to the 16S rRNA gene sequencing analysis,supplementation with SE modulated gut microbiota composition in injured *** conclusion,SE could ameliorate intimal hyperplasia by inhibiting inflammation and vSMCs proliferation through the regulation of the PTEN/PI3K/AKT pathway and modulating the gut microbiome.

关键词： Ascophyllum nodosum Fucus vesiculosus PTEN/PI3K/AKT Restenosis Macrophage Vascular smooth muscle cells Gut microbiota

mIgM-mediated splenic marginal zone B cells targeting of folic acid for immunological evasion

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Acta Pharmaceutica Sinica B 2024年第2期14卷 808-820页

作者： Huan Wang Zhuxuan Jiang Zhiwei Guo Gan Luo Tianhao Ding Changyou Zhan Department of pharmacology School of Basic Medical Sciences&Department of PharmacyShanghai Pudong HospitalFudan UniversityShanghai 200032China Department of Pharmaceutical Sciences School of PharmacyNaval Medical UniversityShanghai 200433China Shanghai Engineering Research Center for Synthetic Immunology Fudan UniversityShanghai 200032China

Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital *** we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B(MZB)*** acid demonstrates avid binding with the Fc domain of immunoglobulin M(IgM),targeting IgM positive MZB cells in vivo to destabilize IgM-B cell receptor(BCR)complex and block immune *** induced anergy of MZB cells by folic acid provides an immunological escaping window for *** conjugation of folic acid with therapeutic proteins and antibodies induces immunological evasion to mitigate the production of anti-drug antibodies,which is a major obstacle to the long-term treatment of biologics by reducing curative effects and/or causing adverse *** acid acts as a safe and effective immunosuppressant via IgM-mediated MZB cells targeting to boost the clinical outcomes of biologics by inhibiting the production of anti-drug antibodies,and also holds the potential to treat other indications that adverse immune responses need to be transiently shut off.

关键词： Membrane-bound IgM Anti-drugantibodies Bcell anergy Folic acid Marginal zoneBcells Bcell receptor Biologics Targeting

GRK2 mediated degradation of SAV1 initiates hyperplasia of fibroblast-like synoviocytes in rheumatoid arthritis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1222-1240页

作者： Paipai Guo Ji Jiang Rui Chu Feng He Mingli Ge Ruhong Fang Qiuyun Guan Huijuan Cheng Chunru Jiang Tiantian Su Zhenduo Zhu Hao Liu Wei Wei Shihao Zhang Qingtong Wang Institute of clinical pharmacology Anhui Medical UniversityKey Laboratory of Anti-inflammatory and Immune MedicineMinistry of EducationCollaborative Innovation Center of Anti-inflammatory and Immune MedicinesHefei 230032China School of pharmacy Bengbu Medical CollegeBengbu 233030China The Third Affiliated Hospital of Anhui Medical University(the First People’s Hospital of Hefei) Hefei 230061China

Hyperplasia and migration of fibroblast-like synoviocytes(FLSs)are the key drivers in the pathogenesis of rheumatoid arthritis(RA)and joint *** Yes-associated protein(YAP),which is a powerful transcription co-activator for proliferative genes,was observed in the nucleus of inflammatory FLSs with unknown upstream *** Gene Expression Omnibus database analysis,it was found that Salvador homolog-1(SAV1),the pivotal negative regulator of the Hippo-YAP pathway,was slightly downregulated in RA ***,SAV1 protein expression is extremely ***,it was revealed that SAV1 is phosphorylated,ubiquitinated,and degraded by interacting with an important serine-threonine kinase,G protein-coupled receptor(GPCR)kinase 2(GRK2),which was predominately upregulated by GPCR activation induced by ligands such as prostaglandin E2(PGE2)in *** process further contributes to the decreased phosphorylation,nuclear translocation,and transcriptional potency of YAP,and leads to aberrant FLSs *** depletion of GRK2 or inhibition of GRK2 by paroxetine rescued SAV1 expression and restored YAP phosphorylation and finally inhibited RA FLSs proliferation and ***,paroxetine treatment effectively reduced the abnormal proliferation of FLSs in a rat model of collagen-induced arthritis which was accompanied by a significant improvement in clinical ***,these results elucidate the significance of GRK2 regulation of Hippo-YAP signaling in FLSs proliferation and migration and the potential application of GRK2 inhibition in the treatment of FLSs-driven joint destruction in RA.

关键词： Rheumatoid arthritis Fibroblast-like synoviocytes G protein-coupled receptor kinase 2 Salvador homolog-1 Yes-associated protein

Enantioselective Synthesis of Benzimidazole Atropisomers Featuring a N-N Axis

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Chinese Journal of Chemistry 2024年第7期42卷 711-718页

作者： Fang-Bei Ge Qi-Kun Yin Chuan-Jun Lu Xuan Xuan Jia Feng Ren-Rong Liu College of Chemistry and Chemical Engineering Qingdao UniversityQingdaoShandong 266071China School of pharmacy Key Laboratory of Molecular Pharmacology and Drug EvaluationMinistry of EducationYantai UniversityYantaiShandong 264005China

Atroposelective synthesis of N-N atropisomers is an emerging area but remains underexplored;in particular,the synthesis of N-N benzimidazole atropisomers is still ***,the first enantioselective synthesis of N-N benzimidazole atropisomers via the palladium-catalyzed de novo construction of benzimidazole skeleton is *** readily available palladium catalyst and biphosphine ligand,a broad range of nonbiaryl benzimidazole and indole-benzimidazole atropisomers were conveniently ac-cessed in high yields and with excellent ***,these N-N benzimidazole atropisomers showed great anti-tumor activity and selectivity to breast cancer MCF-7 *** simple catalytic system,broad substrate scope,high enantioselectivi-ty,and good bioactivity make this approach highly attractive.

关键词： Asymmetric synthesis Atropisomerism Palladium Benzimidazole Antitumor

Insights into spinal muscular atrophy from molecular biomarkers

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Neural Regeneration Research 2025年第7期20卷 1849-1863页

作者： Xiaodong Xing Xinzhu Liu Xiandeng Li Mi Li Xian Wu Xiaohui Huang Ajing Xu Yan Liu Jian Zhang Department of clinical pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina College of pharmacy Chongqing Medical UniversityChongqingChina

Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle *** is one of the most common genetic causes of mortality among infants aged less than 2 *** research is currently receiving more attention,and new candidate biomarkers are constantly being *** review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and *** also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific *** review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future ***,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

关键词： biomarkers disease progression gene-targeting therapy neurofilaments Nusinersen spinal muscular atrophy(SMA) survival motor neuron therapeutic evaluation treatment outcomes