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Tetramic acid-motif natural products from a marine fungus Tolypocladium cylindrosporum FB06 and their anti-Parkinson activities

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Marine Life science & Technology 2024年第1期6卷 84-92页

作者： Yuna Jung Chaesun Kwon Taeyeon Kim Jin Woo Lee Min-Kyoo shin sang Hee shim Natural Products.r.search Institute College of PharmacySeoul National UniversitySeoul 08826Republic of Korea college of pharmacy and research Institute of Pharmaceutical sciences Seoul National UniversitySeoul 08826Republic of Korea college of pharmacy Duksung Women’s UniversitySeoul 01369Republic of Korea

Tetramic acid-containing natural products are attracting significantly increasing attention from biologists and chemists due to their intriguing s.r.ctures and biological *** the present study,two new tetramic acid alkaloids tolypyridone I(1)and tolypyridone J(2),together with five known ones(3–7),were isolated from cultures of a marine fungus Tolypocladium cylindrosporum FB06 isolate obtained from a marine sediment in Beaufort sea of North *** s.r.ctures were elucidated using 1D,2D NMr,and *** configurations were established on the basis of 1H coupling constants.r.EsY correlations and DP4 *** 2 was isolated as mixtures of rotational isomers with C-3 to C-7 axis between 4-hydroxy-2-pyridone and 1-ethyl-3,5-dimethylcyclohexane,hindering *** our unbiased s.r.ening to discover neuroprotective compounds in an in vitro Parkinson’s disease(PD)model,sH-sY5Y dopaminergic cells were treated with isolated compounds followed by treatment with 1-methyl-4-phenylpyridinium(MPP^(+)),a parkinsonian *** tested compounds,F-14329(7)significantly protected cells from MPP^(+)-induced ***^(+)-mediated cell death is known to be related to the regulation of Bcl-2 family proteins,specifically the down-regulation of anti-apoptotic Bcl-2 and the up-regulation of pro-apoptotic Bax *** with 2 mmol/L of MPP^(+)for 24 h significantly reduced Bcl-2 levels compared to control treated with ***,treatment with F-14329(7)attenuated such *** study demons.r.tes that tetramic acid-motif compounds could be potential lead compounds for treating PD.

关键词： Tolypocladium cylindrosporum Tetramic acid Tolypyridone Parkinson’s disease

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Bile acid metabolism and signaling in health and disease:molecular mechanisms and therapeutic targets

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signal Transduction and Targeted Therapy 2024年第5期9卷 2014-2064页

作者： Joshua s.Fleishman sunil Kumar Department of Pharmaceutical sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNYUSA

Bile acids,once considered mere dietary s.r.actants,now emerge as critical modulators of macronutrient(lipid,carbohydrate,protein)metabolism and the systemic pro-inflammatory/anti-inflammatory *** acid metabolism and signaling pathways play a crucial role in protecting against,or if aberrant,inducing cardiometabolic,inflammatory,and neoplastic conditions,s.r.ngly influencing health and *** curative treatment exists for any bile acid influenced disease,while the most promising and well-developed bile acid therapeutic was.r.cently rejected by the ***,we provide a bottom-up approach on bile acids,mechanistically explaining their biochemis.r.,physiology,and pharmacology at canonical and non-canonical *** this mechanistic model of bile acids,we explain how abnormal bile acid physiology drives disease pathogenesis,emphasizing how ceramide synthesis may s.r.e as a unifying pathogenic feature for cardiometabolic *** provide an in-depth summary on pre-existing bile acid receptor modulators,explain their shortcomings,and propose solutions for how they may be ***,we rationalize novel targets for further translational drug discovery and provide future *** than dismissing bile acid therapeutics due to recent setbacks,we believe that there is immense clinical potential and a high likelihood for the future success of bile acid therapeutics.

关键词： metabolism rejected shortcomings

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Nanotherapeutics targeting autophagy regulation for improved cancer therapy

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Acta Pharmaceutica sinica B 2024年第6期14卷 2447-2474页

作者： Yunmeng Liu Yaxin Wang Jincheng Zhang Qikai Peng Xingdong Wang Xiyue Xiao Kai shi college of pharmacy Nankai UniversityTianjin 300350China

The clinical efficacy of current cancer therapies falls short,and there is a pressing demand to integrate new targets with conventional ***,a highly cons.r.ed self-degradation process,has.r.ceived considerable attention as an emerging therapeutic target for *** the rapid development of nanomedicine,nanomaterials have been widely utilized in cancer therapy due to their unrivaled delivery ***,considering the potential benefits of integrating autophagy and nanotechnology in cancer therapy,we outline the latest advances in autophagy-based *** on a brief background related to autophagy and nanotherapeutics and their impact on tumor progression,the feasibility of autophagy-based nanotherapeutics for cancer treatment is ***,emerging nanotherapeutics developed to modulate autophagy are reviewed from the perspective of cell signaling pathways,including modulation of the mammalian target of rapamycin(mTOr)pathway,autophagy-related(ATG)and its complex expression,reactive oxygen species.r.s)and mitophagy,interference with autophagosome-lysosome fusion,and inhibition of hypoxia-mediated *** addition,combination therapies in which nano-autophagy modulation is combined with chemotherapy,phototherapy,and immunotherapy are also ***,the prospects and challenges of autophagy-based nanotherapeutics for efficient cancer treatment are envisioned.

关键词： Autophagy regulation Nanotherapeutic Combination s.r.tegies Cancer therapy signal transduction pathway Delivery s.r.tegies Dual effects Nanomaterials

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Coleus forskohlii shows anti-ps.r.atic activity in imiquimod-induced ps.r.asis.r.ts

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Asian Pacific Journal of Tropical Biomedicine 2024年第9期14卷 382-390,I0002-I0007页

作者： sagarika Majhi Iti Chauhan Deepak Kumar Md.Niyaz Alam Md.s.r.araj Hussain Muzaffar Iqbal Faculty of pharmacy I.T.S College of PharmacyMuradnagarGhaziabadU.P.India Lord Buddha Koshi pharmacy college of pharmacy BaijanathpurNH 107Saharsa(Bihar)852201India Department of Pharmaceutical Chemis.r. College of PharmacyKing Saud UniversityP.O.Box 2457Riyadh 11451Saudi Arabia

Objective:To evaluate anti-ps.r.atic activity of Coleus forskohlii in rats with imiquimod-induced ***:Imiquimod was used to induce ps.r.asis in *** weight,skin thickness,erythema,scaling,spleen weight,and histological alternations were meas.r.d to assess the effect of Coleus ***,an emulgel formulation containing Coleus forskohlii 10%was prepared and characterized along with its ex vivo permeation ***:The emulgel formulation containing Coleus forskohlii 10%had a pH of 5.40±0.36,with optimum s.r.adability of(31.67±2.08)g/(cm·s)and viscosity of(15966.67±1274.10)cps,and enhanced both the rate and the extent of drug permeation through ps.r.atic *** an ex vivo study,the quantity of drug permeated(19.18%),deposited(52.38%),and drug remaining in the donor compartments(28.31%)was *** forskohlii significantly alleviated imiquimod-induced ps.r.asis by increasing glutathione and superoxide dismutase activity,decreasing malondialdehyde and nitric oxide levels,and alleviating histological alternations in rat ***:Coleus forskohlii can alleviate imiquimod-induced ps.r.asis,which may be used as a therapeutic candidate for the treatment of ps.r.asis.

关键词： Ps.r.asis Coleus forskohlii Emulgel Ex vivo Imiquimod Carbopol

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Olfactory dysfunction and its.r.lated molecular mechanisms in Parkinson’s disease

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Neural regeneration research 2024年第3期19卷 583-590页

作者： Yingying Gu Jiaying Zhang Xinru Zhao Wenyuan Nie Xiaole Xu Mingxuan Liu Xiaoling Zhang college of pharmacy Nantong UniversityNantongJiangsu ProvinceChina

Changes in olfactory function are considered to be early biomarkers of Parkinson’s *** dysfunction is one of the earliest non-motor features of Parkinson’s disease,appearing in about 90%of patients with early-stage Parkinson’s disease,and can often predate the diagnosis by ***,olfactory dysfunction should be considered a reliable marker of the ***,the mechanisms.r.sponsible for olfactory dysfunction are currently *** this article,we clearly explain the pathology and medical definition of olfactory function as a biomarker for early-stage Parkinson’s *** the basis of the findings of clinical olfactory function tests and animal model experiments as well as neurotransmitter expression levels,we further characterize the relationship between olfactory dysfunction and neurodegenerative diseases as well as the molecular mechanisms underlying olfactory dysfunction in the pathology of early-stage Parkinson’s *** findings highlighted in this.r.view suggest that olfactory dysfunction is an important biomarker for preclinical-stage Parkinson’s ***,therapeutic drugs targeting non-motor symptoms such as olfactory dysfunction in the early stage of Parkinson’s disease may prevent or delay dopaminergic neurodegeneration and reduce motor symptoms,highlighting the potential of identifying effective targets for treating Parkinson’s disease by inhibiting the deterioration of olfactory dysfunction.

关键词： biomarker early-stage olfactory dis.r.ers olfactory dysfunction Parkinson’s disease

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Elucidating the Degradation Pathways of Human Insulin in the solid state

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Journal of Analysis and Testing 2024年第3期8卷 288-299页

作者： Andrew Fagan Lorraine M.Bateman Joseph P.O'shea Abina M.Crean ssPC the SFI Centre for Pharmaceutical Research School of Pharmacy University College Cork school of pharmacy University College Cork Analytical and Biological Chemis.r. research Facility (ABCrF) University College Cork school of Chemis.r. University College Cork

While there have been significant advances in the development of peptide oral dosage forms in recent years, highlighted by the clinical and commercial success of approved peptides such as.r.belsus?, there remain several barriers in the way of broad range applicability of this approach to peptide delivery. One such barrier includes the poor physical and chemical stability inherent to their s.r.ctures, which persists in the solid state although degradation typically occurs at different rates and via different pathways in comparison to the solution state. Using insulin as a model peptide, this work sought to contribute to the development of analytical techniques for investigating common insulin degradation pathways. Chemically denatured,deamidated and aggregated samples were prepared and used to benchmark circular dichroism spectroscopy, reverse phase HPLC and size exclusion chromatography methods for the investigation of unfolding, chemical modifications and covalent aggregation of the insulin molecule respectively. solid state degraded samples were prepared by heating insulin powder at 60 °C and 75% relative humidity for 1, 3, 5 and 7 d, and the degradation profiles of the samples were evaluated and compared with those obs.r.ed in solution. While no unfolding was obs.r.ed to occur, significant deamidation and covalent aggregation were detected. reductive disulfide bond cleavage using dithiothreitol allowed for separation of the insulin A-and B-chains,offering a facile yet novel means of assessing the mechanisms of deamidation and covalent aggregation occurring in the solid state.

关键词： Biopharmaceutical analysis Covalent aggregation Deamidation Disulfide cleavage Insulin solid state stability

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CuIns_(2)quantum-dot-modified g-C_(3)N_(4)s-scheme heterojunction photocatalyst for hydrogen production and tetracycline degradation

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Journal of Materials science & Technology 2024年第5期172卷 145-155页

作者： Jingjing Zhang Yue Zhao Kezhen Qi shu-yuan Liu college of pharmacy Dali UniversityDali 671000China Department of Pharmacology Shenyang Medical CollegeShenyang 110034China

CuIns_(2)quantum-dot(CIs QD)-modified g-C_(3)N_(4)(CN)catalysts(CIs/CN)were prepared with the aid of an in-situ growth *** as-obtained photocatalysts were explored by meas.r.ng their crystallinity,s.r.ace morphology,binding energy and light abs.r.tion *** photocatalytic efficiency of the pho-tocatalysts was evaluated through photocatalytic water splitting for hydrogen production and tetracycline(TC)antibiotic degradation under the simulated solar light and visible light *** optimized sample(10CIs/CN)showed the best photocatalytic activity:producing 102.4μmol g^(-1)h^(-1)of hydrogen in 1 h,or degrading 52.16%of TC in 120 min,which were respectively 48 or 3.4 times higher than the photocatalytic activity of CN *** enhancement in the efficiency of the composite system was prin-cipally accredited to the enlargement of light abs.r.tion,the more effective in charge transfer and the dropping of the charge carrier pair recombination through a formed s-scheme heterojunctional *** work is an effort to adjust CN-based polysulfide QD for speedy *** enriched photo-catalytic activity grants a new sense for adjusting the optical properties of CN.

关键词： CuIns_(2)QDs g-C_(3)N_(4) Photocatalysis Hydrogen production s-scheme heterojunction

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saponin Ⅰ from shuitianqi(rhizoma schizocapasae Plantagineae) inhibits metastasis by negatively regulating the transforming growth factor-β1/smad7 network and epithelial-mesenchymal transition in the intrahepatic metastasis Bagg's Albino/c mouse model

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Journal of Traditional Chinese Medicine 2024年第4期44卷 642-651页

作者： LYU Meixian ZHOU Huan ZHI Limin ZHOU Jinling GAN rizhi QIN Yanping HE Nengting ZUO Qiqi LI Hao DONG Min LIANG Gang Pharmaceutical college Guangxi Medical UniversityNanning 530022China Department of pharmacy Affiliated Tumor Hospital of Guangxi Medical UniversityNanning 530022China Drug clinical trial Facility office the People's Hospital of Guangxi Zhuang Autonomous RegionNanning 530022China college of pharmacy Guangxi University of Chinese MedicineNanning 530022China Department of pharmacy the Second Affiliated Hospital of Guangxi Medical UniversityNanning 530005China Department of pharmacy People's Hospital of Guangxi HezhouHezhou 542899China Department of pharmacy Guangzhou Women and Children's Medical Center Liuzhou HospitalLiuzhou 545000China Department of pharmacy First Affiliated Hospital of Gannan Medical UniversityGannan 341000China

OBJECTIVE:To examine the influence of saponinⅠfrom shuitianqi(rhizoma schizocapasae Plantagineae)(ssPHⅠ)on hepatocellular carcinoma(HCC)metastasis,and to elucidate the underlying ***:The intrahepatic metastasis Bagg's Albino/c(BALB/c)mouse model was established with human hepatocellular carcinomas(HepG2)cells,then treated with normal saline(once per day),cisplatin(2 mg/kg,once every 2 d),and ssPHⅠ(25,50,and 75 mg/kg,once per day).Then,we assessed alterations in the hepatic pathology and target protein expressions in the intrahepatic metastasis BALB/c mouse model using a s.r.es of molecular biology ***:Based on our analysis,ssPHⅠsignificantly alleviated hepatocyte necrosis and tumor cells ***,ssPHⅠsuppressed extracellular matrix(ECM)degradation and angiogenesis via a decrease in matrix etalloproteinase-2(MMP-2),MMP-9,CD31,CD34,and vascular endothelial growth factor(VEGF)***,ssPHⅠrepressed invasion and metastasis by suppressing the transforming growth factor-β1(TGF-β1)/smad7 axis and epithelial-mesenchymal transition(EMT),as evidenced by the scarce TGF-β1,Ncadherin,and Vimentin expressions,and elevated smad7 and E-cadherin ***:The ssPHⅠ-mediated negative regulation of the TGF-β1/smad7 axis and EMT are critical for the inhibition of HCC invasion and metastasis.

关键词： carcinoma,hepatocellular epithelial-mesenchymal transition transforming growth factor beta1 smad7 protein saponin I from shuitianqi(rhizoma schizocapasae Plantagineae)

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Phase-dependent lithium-alloying reactions for lithium-metal batteries

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Chinese Chemical Letters 2024年第4期35卷 1-2页

作者： shu Lin Kezhen Qi college of pharmacy Dali UniversityDali 671000China

With the increasing demand for higher energy lithium-ion batteries (LIBs), it is imperative to develop high-capacity electrode materials [1–4]. Due to the unique electrochemical Li-alloying reactions, Li-alloys offer high theoretical capacity, especially lithiumrich phase alloys, which exceeds the theoretical capacity of graphite anodes [5–7]. Phase-transition, which significantly influences lithium alloy reactions, determines high voltage hysteresis,low Coulombic efficiency (CE), and short cycling life [8,9].

关键词： alloying alloys cycling

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Current perspective on amyloid aggregation accelerating properties of the artificial butter flavoring,diacetyl

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Neural regeneration research 2024年第10期19卷 2113-2114页

作者： Ashish P.Vartak swati s.More Center for Drug Design College of PharmacyUniversity of MinnesotaMinneapolisMNUSA

The amyloid—what peptide can resist its entropic bliss?Without kinetic barricades and chaperones,most peptides would simply tumble down that *** amyloid-β(Aβ) peptides are understood to underlie the hallmark pathology of Alzheimer's disease(AD) and are considered one of the causative factors for neurodegeneration and cognitive *** affects critical connected s.r.ctures within the brain that are responsible for memory,language,and social behavior.

关键词： amyloid Alzheimer Aβ

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