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Synthetic high-density lipoprotein(sHDL):a bioinspired nanotherapeutics for managing periapical bone inflammation

International Journal of Oral Science 2024年第3期16卷 460-470页

作者： Renan Dal-Fabbro Minzhi Yu Ling Mei Hajime Sasaki Anna Schwendeman Marco C.Bottino Department of Cariology Restorative Sciencesand EndodonticsSchool of DentistryUniversity of MichiganAnn ArborMIUSA Department of Pharmaceutical Sciences College of Pharmacy and Biointerfaces InstituteUniversity of MichiganAnn ArborMIUSA Department of Biomedical Engineering College of EngineeringUniversity of MichiganAnn ArborMIUSA

Apical periodontitis(AP)is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth(i.e.,dental pulp tissue),resulting in inflammation and apical bone resorption affecting 50%of the worldwide population,with more than 15 million root canals performed annually in the United *** treatment involves cleaning and decontaminating the infected tissue with chemo-mechanical approaches and materials introduced years ago,such as calcium hydroxide,zinc oxide–eugenol,or even formalin ***,we present,for the first time,a nanotherapeutics based on using synthetic highdensity lipoprotein(sHDL)as an innovative and safe strategy to manage dental bone *** application in concentrations ranging from 25μg to 100μg/mL decreases nuclear factor Kappa B(NF-κB)activation promoted by an inflammatory stimulus(lipopolysaccharide,LPS).Moreover,sHDL at 500μg/mL concentration markedly decreases in vitro osteoclastogenesis(Paling pathway facing LPS stimulation,mainly by downregulating at least 3-fold the pro-inflammatory genes,such as Il1b,Il1a,Il6,Ptgs2,and *** vivo,the lipoprotein nanoparticle applied after NaOCl reduced bone resorption volume to(1.3±0.05)mm3 and attenuated the inflammatory reaction after treatment to(1090±184)cells compared to non-treated animals that had(2.9±0.6)mm3(P=0.0123)and(2443±931)cells(P=0.004),thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation.

关键词： inflammation lipoprotein markedly

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Förster resonance energy transfer reveals phillygenin and swertiamarin concurrently target AKT on different binding domains to increase the anti-inflammatory effect

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Chinese Chemical Letters 2024年第5期35卷 207-212页

作者： Xiaoyao Ma Jinling Zhang Ge Fang He Gao Jie Gao Li Fu Yuanyuan Hou Gang Bai State Key Laboratory of Medicinal Chemical Biology College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjin 300000China college of Life Health Dalian UniversityDalian 116622China Dalian Fusheng Pharmaceutical Co. Ltd.Dalian 116000China

The clinical benefit of combination therapy is significant,but it is not easy to define the mechanism of complexity and *** studies illustrate that phillygenin(Phi)binds in the allosteric inhibit pocket of protein kinase B(AKT),and swertiamarin(Swe)acts on the pleckstrin homology(PH)domain of ***,the combined synergistic effect of relieving the inflammatory response has yet to be *** on high sensitivity,specificity and fast-responsibility fluorescent sensors,the Förster resonance energy transfer(FRET)technique offers a route to provide clear insights into physiological and pathological *** the study,molecular docking,the fluorescent probes of Phi and Swe for FRET were designed and *** analysis shown that Swe and Phi concurrently acted on the PH domain and allosterically inhibited pocket of AKT,*** combination of Swe and Phi significantly increased the heat stability of AKT and decreased protease-induced *** lipopolysaccharides(LPS)-induced mice and cells,the combination arrested AKT activation,nuclear factor kappa-B(NF-κB)phosphorylation,and the expression of tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and *** conclusion,FRET revealed Phi and Swe concurrently targeted AKT on different domains and the combination of Phi and Swe enhanced the anti-inflammatory effect.

关键词： FRET Swertiamarin Phillygenin AKT Anti-inflammation Combinatorial drug

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Insights into the anorexic mechanism of Khat:an integrated in vivo,ex vivo,and in silico investigations

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Traditional Medicine Research 2024年第10期9卷 36-51页

作者： Ahmed ali Jerah Manal Mohamed Elhassan Taha Abdullah Farasani Sivakumar Sivagurunathan Moni Emad Sayed Shaheen Andleeb Khan Ibrahim Abdo Khardali Magbool Oraiby Heyam Mohamed ali Sidahmed Siddig Ibrahim Abdelwahab Department of Medical Laboratory Technology College of Applied Medical SciencesJazan UniversityJazan 45142Saudi Arabia Health Research Centre Jazan UniversityJazan 45142Saudi Arabia Department of Pharmaceutics College of PharmacyJazan UniversityJazan 45142Saudi Arabia Department of Biosciences Faculty of ScienceIntegral UniversityLucknow 226026India Poison Control and Medical Forensic Chemistry Center General Directorate of Health AffairsJazan 45142Saudi Arabia Department of Pharmaceutical Chemistry Faculty of PharmacyAl-Neelain UniversityKhartoum 16458Sudan

Background:Chewing Khat(Catha edulis)releases cathine and cathinone,which may reduce appetite via an unknown *** study investigated the peripheral and central effects of fresh leaves and buds of Catha edulis water extract(CEWE)on appetite biomarkers,gene expression,and body weight,using in vivo,ex vivo,and in silico ***:Rats of both sexes were orally administered CEWE at different doses and durations in three different *** chromatography-mass spectroscopy(LC-MS)-MS was used to detect cathinone and cathine in the murine *** effect of Khat on serotonin receptors was studied in isolated rat fundus *** of the two Khat ligands was performed on G(The 5-hydroxytryptamine-type 2C receptor(5-HT2C)in an agonist-bound active conformation)and H(5-HT2C in an antagonist-bound inactive conformation)proteins to determine which ligands are most likely to act as agonists or ***:Significant differences(P0.05).The expression of the ghrelin and leptin genes was also unaffected,but the expression of the 5-hydroxytryptamine(5-HT)gene decreased(Pal applications.

关键词： Catha edulis appetite leptin ghrelin 5-hydroxytryptamine molecular docking

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Modulation of p75 neurotrophin receptor mitigates brain damage following ischemic stroke in mice

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Neural Regeneration Research 2024年第10期19卷 2093-2094页

作者： Golnoush Mirzahosseini Tauheed Ishrat Department of Anatomy and Neurobiology College of MedicineThe University of Tennessee Health Science CenterMemphisTNUSA Pharmaceutical Sciences College of PharmacyThe University of Tennessee Health Science CenterMemphisTNUSA Neuroscience Institute The University of Tennessee Health Science CenterMemphisTNUSA

Stroke is a significant leading cause of death and disability in the United States(Tsao et al.,2022).Approximately 87% of strokes fall into the ischemic category,mainly caused by arterial blockage(Jayaraj et al.,2019).although the only FDA-approved effective medication is tissue plasminogen activator(tPA),it should be administrated within 4.5 hours of ischemic ***,tPA has been an integral part of managing acute ischemic stro ke.

关键词： damage arterial death p75

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Adsorption,in vitro digestion and human gut microbiota regulation characteristics of three Poria cocos polysaccharides

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Food Science and Human Wellness 2024年第3期13卷 1685-1697页

作者： Fangming Zhang Hui Zheng Tao Zheng Pan Xu Yao Xu Yuxin Cao Fan Jia Yiqiong Zeng Yubing Fan Kai He Xinwen Dai Fengfei Hou Yong Yang college of pharmacy Hunan University of Chinese MedicineChangsha 410208China School of Pharmaceutical Science Hunan University of MedicineHuaihua 418000China Hunan Fuling Engineering Technology Research Center Huaihua 418100China

Poria cocos(PC)is a famous traditional Chinese medicine(TCM)and a widely used healthcare ingredient,which has antiobesity,enhancing immunity and improving sleep ***,only water-soluble poria polysaccharide(WSP)is extracted and applied for clinical application,while insoluble polysaccharide(alkali-soluble poria polysaccharide,ASP)is discarded as herb ***,the whole PC has also been historically utilized as functional herbal *** the beneficial role of dietary fiber and the traditional use of PC,ASP may also contribute substantially to the therapy function of *** to WSP,little attention has been paid to ASP and ASP modified product carboxymethyl poria polysaccharide(CMP)which has been used as an antitumor adjuvant *** this study,the oil,cholesterol,metal ions and polyphenols adsorption ability,in vitro simulated digestive and the gut microbiota fermentation characteristics of WSP,ASP and CMP were studied to evaluate the functional values of three *** polysaccharides(PCPs).The results showed that all three PCPs had good adsorption capacity on cholesterol,polyphenols and metal ions(Cd^(2+)/Zn^(2+)/Mg^(2+)),among which ASP showed the highest capacity than WSP and *** adsorption capacity of all three PCPs on heavy metal ions(Cd^(2+)/Zn^(2+))was stronger than that of non-heavy metal ions(Mg^(2+));The in vitro digestibility of all three PCPs was very low,but WSP was slightly higher than ASP and CMP;Moreover,the indigestible residue of all three PCPs could improve the richness and diversity of gut microbiota,among which ASP had the greatest *** general,ASP and CMP could significantly promote the proliferation of some probiotics and inhibit the growth of some harmful *** gut microbiota diversity of CMP was reduced,but the richness of probiotics,especially Parabacteroides distasonis was significantly enhanced compared with the ASP group,and the growth of harmful bacteria Klebsiella pneumoniae was inh

关键词： Poria cocos polysaccharides alkali-soluble poria polysaccharide Carboxymethyl poria polysaccharide Adsorption characteristics In vitro simulated digestion In vitro simulated gut microbiota fermentation

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The dopaminergic system and alzheimer's disease

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Neural Regeneration Research 2025年第9期20卷 2495-2512页

作者： Yuhan Zhang Yuan Liang Yixue Gu International Medical college Chongqing Medical UniversityChongqingChina college of pharmacy Chongqing Medical UniversityChongqingChina Department of Neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqing Key Laboratory of NeurologyChongqingChina

alzheimer's disease is a common neurodegenerative disorder in older *** its prevalence,its pathogenesis remains unclea *** addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this *** is a crucial catecholaminergic neurotransmitter in the human ***-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical *** r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive *** review summarizes the role of the dopaminergic system in the pathology of alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related *** aim of this review is to provide insights into the potential connections between the dopaminergic system and alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.

关键词： adverse drug reaction alzheimer's disease catecholamine dopamine receptor dopamine receptor heterodimers dopaminergic system neurodegenerative disease neurotransmitter signaling pathways traditional Chinese medicine treatment

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Modulating the electrode–electrolyte interface enables switchable selectivity in electrocatalytic furfural reduction

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Science China Chemistry 2024年第10期67卷 3193-3194页

作者： Jingfang Zhang Yi Huang Engineering Research Center of Phosphorus Resources Development and Utilization of Ministry of Education School of Chemical Engineering&PharmacyWuhan Institute of TechnologyWuhan 430205China college of Chemistry Central China Normal UniversityWuhan 430079China

Furfural(FF),an important bio-based platform molecule,can be valorized to high-value-added chemicals(e.g.,furfuryl alcohol(FA)or 2-methylfuran(MF))through catalytic hydrogenation[1].The traditional thermocatalytic transformation of FF always requires high-temperature and highpressure conditions[2].Accordingly,electrocatalytic hydrogenation is emerging as a promising approach for the selective reduction of FF to FA or MF under environmentally friendly and benign conditions.

关键词： hydrogenation electrolyte selectivity

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Polysaccharides from Chinese herbal medicine:a review on the hepatoprotective and molecular mechanism

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Chinese Journal of Natural Medicines 2024年第1期22卷 4-14页

作者： LI Jifeng GUO Haolin DONG Ying YUAN Shuo WEI Xiaotong ZHANG Yuxin DONG Lu WANG Fei BAI Ting YANG Yong Dalian Key Laboratory of Chronic Disease Research Center Dalian UniversityDalian 116622China Key Laboratory of Natural Medicines of the Changbai Mountain Ministry of EducationCollege of PharmacyYanbian UniversityYanji 133002China

Polysaccharides,predominantly extracted from traditional Chinese medicinal herbs such as Lycium barbarum,Angelica sinensis,Astragalus membranaceus,Dendrobium officinale,Ganoderma lucidum,and Poria cocos,represent principal bioactive constituents extensively utilized in Chinese *** compounds have demonstrated significant anti-inflammatory capabilities,especially anti-liver injury activities,while exhibiting minimal adverse *** review summarized recent studies to elucidate the hepatoprotective efficacy and underlying molecular mechanisms of these herbal *** underscored the role of these polysaccharides in regulating hepatic function,enhancing immunological responses,and improving antioxidant capacities,thus contributing to the attenuation of hepatocyte apoptosis and liver *** of molecular pathways in these studies revealed the intricate and indispensable functions of traditional Chinese herbal polysaccharides in liver injury ***,this review provides a thorough examination of the hepatoprotective attributes and molecular mechanisms of these medicinal polysaccharides,thereby offering valuable insights for the advancement of polysaccharide-based therapeutic research and their potential clinical applications in liver disease treatment.

关键词： Polysaccharides Hepatoprotective Chinese herbal medicine Mechanism

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Different processing methods and pharmacological effects of Atractylodis Rhizoma

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Chinese Journal of Natural Medicines 2024年第8期22卷 756-768页

作者： GUO Dongmei XU Kang WAN Qianyun YU Songyang MA Chaoyang ZHANG Baohui LIU Yanju QU Linghang college of pharmacy Hubei University of Chinese MedicineWuhan 430065China Center for Hubei TCM Processing Technology Engineering Wuhan 430065China Hubei Shizhen Laboratory Wuhan 430065China

Atractylodis Rhizoma,a traditional Chinese medicine with an extensive history of treating gastrointestinal disorders and other diseases,undergoes various processing methods in China to enhance its therapeutic efficacy for specific ***,a comprehensive report detailing the changes in chemical composition and pharmacological effects due to these processing methods is currently *** article provides a systematic review of the commonly employed processing techniques for Atractylodis Rhizoma,including raw Atractylodis Rhizoma(SCZ),bran-fried Atractylodis Rhizoma(FCZ),deep-fried Atractylodis Rhizoma(JCZ),and rice water-processed Atractylodis Rhizoma(MCZ).It examines the alterations in chemical constituents and pharmacological activities resulting from these processes and elucidates the mechanisms of action of the primary components in the various processed forms of Atractylodis Rhizoma in the treatment of gastrointestinal diseases.

关键词： Atractylodis Rhizoma Processing method Pharmacological effect Change in chemical composition Gastrointestinal disease

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5S-Heudelotinone alleviates experimental colitis by shaping the immune system and enhancing the intestinal barrier in a gut microbiota-dependent manner

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2153-2176页

作者： Qing Meng Jianshuang Guo Ke Lv Yang Liu Jin Zhang Mingyue Li Xirui Cheng Shenghua Chen Xiaoguang Huo Quan Zhang Yue Chen Jing Li State Key Laboratory of Medicinal Chemical Biology College of PharmacyNankai UniversityTianjin 300353China college of Chemistry and Frontiers Science Center for New Organic Matter Haihe Laboratory of Sustainable Chemical TransformationsNankai UniversityTianjin 300071China Accendatech Company Ltd.Tianjin 300193China

Aberrant changes in the gut microbiota are implicated in many diseases,including inflammatory bowel disease(IBD).Gut microbes produce diverse metabolites that can shape the immune system and impact the intestinal barrier integrity,indicating that microbe-mediated modulation may be a promising strategy for preventing and treating *** fecal microbiota transplantation and probiotic supplementation are well-established IBD therapies,novel chemical agents that are safe and exert strong effects on the gut microbiota are urgently ***,we report the total synthesis of heudelotinone and the discovery of 5S-heudelotinone(an enantiomer)as a potent agent against experimental colitis that acts by modulating the gut microbiota.5S-Heudelotinone alters the diversity and composition of the gut microbiota and increases the concentration of short-chain fatty acids(SCFAs);thus,it regulates the intestinal immune system by reducing proinflammatory immune cell numbers,and maintains intestinal mucosal integrity by modulating tight junctions(TJs).Moreover,5S-heudelotinone(2)ameliorates colitis-associated colorectal cancer(CAC)in an azoxymethane(AOM)/dextran sulfate sodium(DSS)-induced in situ carcinoma ***,these findings reveal the potential of a novel natural product,namely,5S-heudelotinone,to control intestinal inflammation and highlight that this product is a safe and effective candidate for the treatment of IBD and CAC.

关键词： 5S-heudelotinone Total synthesis Inflammatory bowel disease Gut microbiota Short-chain fatty acids Immune system Intestinal barrier Drug discovery

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