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Dried-leaf Artemisia annua: A practical malaria therapeutic for developing countries?

World journal of Pharmacology 2014年第4期3卷 39-55页

作者： pamela j weathers Melissa Towler Ahmed Hassanali Pierre Lutgen Patrick Ogwang Engeu Department of Biologyand Biotechnology Worcester Polytechnic Institute Worcester MA 01609 United States School of Pure and Applied Sciences Kenyatta University IFBV-BELHERB PO Box 98 L-6908 Nieder-anven Luxembourg Natural Chemotherapeutics Research Institute Ministry of Health PO Box 4864 Kampala Uganda

Artemisinin from the plant Artemisia annua （A. annua） L., and used as artemisinin combination therapy （ACT）, is the current best therapeutic for treating malaria, a disease that hits children and adults especially in developing countries. Traditionally, A. annua was used by the Chinese as a tea to treat “fever”. More recently, investiga-tors have shown that tea infusions and oral consumption of the dried leaves of the plant have prophylactic and therapeutic effcacy. The presence of a complex matrix of chemicals within the leaves seems to enhance both the bioavailability and effcacy of artemisinin. Although about 1000-fold less potent than artemisinin in their antiplasmodial activity, these plant chemicals are mainly small molecules that include other artemisinic compounds, terpenes （mainly mono and sesqui）, favonoids, and polyphenolic acids. In addition, polysaccharide constituents of A. an-nua may enhance bioavailability of artemisinin. Rodent pharmacokinetics showed longer T？ and Tmax and greater Cmax and AUC in Plasmodium chabaudi -infected mice treated with A. annua dried leaves than in healthy mice. Pharmacokinetics of deoxyartemisinin, a liver metabolite of artemisinin, was more inhibited in infected than in healthy mice. In healthy mice, artemisinin serum levels were 〉 40-fold greater in dried leaf fed mice than those fed with pure artemisinin. Human trial data showed that when delivered as dried leaves, 40-fold less artemisinin was required to obtain a therapeutic response compared to pure artemisinin. ACTs are still unaffordable for many malaria patients, and cost estimates for A. annua dried leaf tablet production are orders of magnitude less than for ACT, despite improvements in the production capacity. Considering that for 〉 2000 years this plant was used in traditional Chinese medicine for treatment of fever with no apparent appearance of artemisinin drug resistance, the evidence argues for inclusion of affordable A. annua dried leaf tablets into the a

关键词： Malaria Infectious disease Artemisia annua Artemisinin Combination therapy Artemisinin combination therapy

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Artemisinin and artemisinin derivatives as anti-fibrotic therapeutics

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Acta Pharmaceutica Sinica B 2021年第2期11卷 322-339页

作者： David Dolivo pamela weathers Tanja Dominko Department of Surgery Northwestern University-Feinberg School of MedicineChicagoIL 60611USA Department of Biology and Biotechnology Worcester Polytechnic InstituteWorcesterMA 01609USA

Fibrosis is a pathological reparative process that can occur in most organs and is responsible for nearly half of deaths in the developed *** considerable research,few therapies have proven effective and been approved clinically for treatment of *** compounds are best known as antimalarial therapeutics,but they also demonstrate antiparasitic,antibacterial,anticancer,and antifibrotic *** we summarize literature describing anti-fibrotic effects of artemisinin compounds in in vivo and in vitro models of tissue fibrosis,and we describe the likely mechanisms by which artemisinin compounds appear to inhibit cellular and tissue processes that lead to *** consider alternative routes of administration of artemisinin for treatment of internal organ fibrosis,we also discuss the potential for more direct oral delivery of Artemisia plant material to enhance bioavailability and efficacy of artemisinin compared to administration of purified artemisinin drugs at comparable *** is our hope that greater understanding of the broad anti-fibrotic effects of artemisinin drugs will enable and promote their use as therapeutics for treatment of fibrotic diseases.

关键词： Fibrosis Artemisia Artemisinin Artesunate Fibroblast Myofibroblast Scar TGF-β

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Iron regulatory protein 1: the deadly switch of ferroptosis

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Neural Regeneration Research 2024年第3期19卷 477-478页

作者： Daniel A.Bórquez pamela j.Urrutia Center for Biomedical Research Faculty of MedicineUniversidad Diego PortalesSantiagoChile Institute of Nutrition&Food Technology(INTA) Universidad de ChileSantiagoChile Geroscience Center for Brain Health and Metabolism SantiagoChile

Ferroptosis,an iron-dependent cell death:Ferroptosis is a type of regulated necrosis,characterized by redox-active iron accumulation and increased free radical production derived by Fenton chemistry,that triggers oxidation of polyunsaturated fatty acids in phospholipids,loss of cellular membranes integrity,and leakage of intracellular contents.

关键词： integrity switch Iron

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Iron,the endolysosomal system and neuroinflammation:a matter of balance

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Neural Regeneration Research 2022年第5期17卷 1003-1004页

作者： Daniel A.Bórquez pamela j.Urrutia Marco T.Núñez Center for Biomedical Research Faculty of MedicineUniversidad Diego PortalesSantiagoChile Department of Biology Faculty of SciencesUniversidad de ChileSantiagoChile

Iron accumulation and neuroinflammation are cardinal features of many neurodegenerative diseases(Urrutia et al.,2021).However,the hierarchy in the pathogenic mechanisms and the molecular connections between these proc... 详细信息

关键词： Iron system showing

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Relationship between oxidative stress and hepatic glutathione levels in ethanol-mediated apoptosis of polarized hepatic cells

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World journal of Gastroenterology 2009年第21期15卷 2609-2616页

作者： Benita L McVicker pamela L Tuma Kusum K Kharbanda Serene ML Lee Dean j Tuma Liver Study Unit Department of Veterans Affairs Medical Center and Department of Internal Medicine and Biochemistry & Molecular Biology University of Nebraska Medical Center Department of Biology The Catholic University of America Department of Internal Medicine and Biochemistry & Molecular Biology University of Nebraska Medical Center

AIM： To investigate the role of reactive oxygen species （ROS） in ethanol-mediated cell death of polarized hepatic （WlF-B） cells.METHODS： In this work, WIF-B cultures were treated with pyrazole （inducer of cytochrome P4502E1, CYP2E1） and/or L-buthionine sulfoximine （BSO）, a known inhibitor of hepatic glutathione （GSH）, followed by evaluation of ROS production, antioxidant levels, and measures of cell injury （apoptosis and necrosis）.RESULTS： The results revealed that ethanol treatment alone caused a significant two-fold increase in the activation of caspase-3 as well as a similar doubling in ROS. When the activity of the CYP2E1 was increased by pyrazole pretreatment, an additional two-fold elevation in ROS was detected. However, the CYP2EIrelated ROS elevation was not accompanied with a correlative increase in apoptotic cell injury, but rather was found to be associated with an increase in necrotic cell death. Interestingly, when the thiol status of the cells was manipulated using BSO, the ethanol-induced activation of caspase-3 was abrogated. Additionally, ethanol-treated cells displayed enhanced susceptibility to Fas-mediated apoptosis that was blocked by GSH depletion as a result of diminished caspase-8 activity.CONCLUSION： Apoptotic cell death induced as a consequence of ethanol metabolism is not completely dependent upon ROS status but is dependent on sustained GSH levels,

关键词： WIF-B cells Alcohol Fas/CD95 Glutathi-one Caspase

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The role of Smad7 in oral mucositis

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Protein & Cell 2015年第3期6卷 160-169页

作者： Li Bian Gangwen Han Carolyn W. Zhao pamela j. Garl Xiao-jing Wang Department of Pathology The First Affiliated Hospital of Kunming Medical University Kunming 650032 China Department of Pathology University of Colorado Anschutz. Medical Campus Aurora CO 80203 USA Department of Dermatology The Second Hospital of Shandong University Jinan 250033 China

Oral mucositis, a severe oral ulceration, is a common toxic effect of radioor chemoradio-therapy and a limiting factor to using the maximum dose of radiation for effective cancer treatment. Among cancer patients, at least 40% and up to 70%, of individuals treated with standard chemotherapy regimens or upper-body radiation, develop oral mucositis. To date, there is no FDA approved drug to treat oral mucositis in cancer patients. The key challenges for oral mucositis treatment are to repair and protect ulcerated oral mucosa without promoting cancer cell growth. Oral mucositis is the result of complex, multifaceted pathobiology, involving a series of signaling pathways and a chain of interactions between the epithelium and submucosa. Among those pathways and interactions, the activation of nuclear factor-kappa B （NF-KB） is critical to the inflamma- tion process of oral mucositis. We recently found that activation of TGFβ （transforming growth factor β） signaling is associated with the development of oral mucositis. Smad7, the negative regulator of TGFβ signaling, inhibits both NF-KB and TGFβ activation and thus plays a pivotal role in the prevention and treatment of oral mucositis by attenuating growth inhibition, apoptosis, and inflammation while promoting epithelial migration. The major objective of this review is to evaluate the known functions of Smad7, with a particular focus on its molecular mechanisms and its function in blocking multiple pathological processes in oral mucositis.

关键词： Smad7 oral mucositis cancer TGFβ,NF-κB

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Nicotinamide mononucleotide:a potential effective natural compound against insulin resistance

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Signal Transduction and Targeted Therapy 2021年第9期6卷 2609-2610页

作者： julian Roos julia Zinngrebe pamela Fischer-Posovszky Department of Pediatrics and Adolescent Medicine Ulm University Medical CenterUlmGermany

Recently,a study published in Science by Yoshino et al.1 reported on a randomized,placebo-controlled,double-blind clinical trial to examine the effects of a 10-week nicotinamide mononucleotide(NMN)administration on human metabolism in 25 postmenopausal overweight or obese women with *** revealed positive effects of NMN on insulin sensitivity,insulin signalling,and tissue remodelling in skeletal muscle.

关键词： metabolism clinical

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Magnetically responsive nanofibrous ceramic scaffolds for on-demand motion and drug delivery

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Bioactive Materials 2022年第9期7卷 372-381页

作者： Yonggang Zhang jiaping Li pamela Habibovic Department of Instructive Biomaterials Engineering Maastricht UniversityMERLN Institute for Technology-Inspired Regenerative MedicineUniversiteitssingel 406229 ERMaastrichtthe Netherlands Department of Complex Tissue Regeneration Maastricht UniversityMERLN Institute for Technology-Inspired Regenerative MedicineUniversiteitssingel 406229 ERMaastrichtthe Netherlands

Smart biomaterials,featuring not only bioactivity,but also dynamic responsiveness to external stimuli,are desired for biomedical applications,such as regenerative medicine,and hold great potential to expand the boundaries of the modern clinical ***,a magnetically responsive three-dimensional scaffold with sandwich structure is developed by using hydroxyapatite(HA)nanowires and ferrosoferric oxide(Fe_(3)O_(4))nanoparticles as building *** magnetic HA/Fe_(3)O_(4) scaffold is fully inorganic in nature,but shows polymeric hydrogel-like characteristics including a 3D fibrous network that is highly porous(>99.7%free volume),deformable(50%deformation)and elastic,and tunable *** magnetic HA/Fe3O4 scaffold has been shown to execute multimodal motion upon exposure to an external magnetic field including shape transformation,rolling and *** addition,we have demonstrated that the magnetic scaffold can serve as a smart carrier for remotely controlled,on-demand delivery of compounds including an organic dye and a ***,the magnetic scaffold has exhibited good biocompatibility,supporting the attachment and proliferation of human mesenchymal stromal cells,thereby showing great potential as smart biomaterials for a variety of biomedical applications.

关键词： Hydroxyapatite Magnetic Responsive Drug delivery Cell culture

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Kitchen waste valorization through a mildtemperature pretreatment to enhance biogas production and fermentability:Kinetics study in mesophilic and thermophilic regimen

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journal of Environmental Sciences 2020年第3期32卷 167-179页

作者： Agata Gallipoli Camilla MBraguglia Andrea Gianico Daniele Montecchio pamela Pagliaccia Water Research Institute IRSA-CNR Area Della Ricerca RM100015 MonterotondoRomaItaly

Biowaste valorization through anaerobic digestion is an attractive option to achieve both climate protection goals and renewable energy *** this paper,a complete set of batch trials was carried out on kitchen waste to investigate the effects of mild thermal pretreatment,temperature regimen and substrate/inoculum *** pretreatment was effective in the solubilisation of macromolecular fractions,particularly *** ability of the theoretical methodologies in estimating hydrogen and methane yields of complex substrates was evaluated by comparing the experimental results with the theoretical *** the single batch configuration,a significant initial hydrogen production was observed,prior to methane *** pretreatment effect was the gain in hydrogen production;the extent was highly variable according to the other parameters *** hydrogen yields,up to 113 mL H2/g VSfed,were related to the prompt transformation of soluble *** regimen resulted,as expected,in faster digestions(up to 78 mL CH4/gVS/day) and sorted out pH *** relatively low methane yields(342-398 mL CH4/g VSfed) were the result of the consistent lignocellulosic content and low lipid *** pretreatment proved to be a promising option for the enhancement of hydrogen production in food waste dark fermentation.

关键词： Kitchen waste Hydrogen Methane Thermal pretreatment Kinetics Thermophilic regimen

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Mast cells as rapid innate sensors of cytomegalovirus by TLR3/TRIF signaling-dependent and -independent mechanisms

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Cellular & Molecular Immunology 2015年第2期12卷 192-201页

作者： Marc Becker Niels AW Lemmermann Stefan Ebert pamela Baars Angelique Renzaho jurgen Podlech Michael Stassen Matthias j Reddehase Institute for Immunology Research Center for Immunotherapy (FZI) at the University Medical Center of the Johannes Gutenberg University Mainz Germany Institute for Virology Research Center for Immunotherapy (FZI) at the University Medical Center of the Johannes Gutenberg University Mainz Germany These authors contributed equally to this work Co-senior authors

The succinct metaphor,‘the immune system＇s loaded gun＇, has been used to describe the role of mast cells （MCs） due to their storage of a wide range of potent pro-inflammatory and antimicrobial mediators in secretory granules that can be released almost instantly on demand to fight invaders. Located at host-environment boundaries and equipped with an arsenal of pattern recognition receptors, MCs are destined to be rapid innate sensors of pathogens penetrating endothelial and epithelial surfaces. Although the importance of MCs in antimicrobial and antiparasitic defense has long been appreciated, their role in raising the alarm against viral infections has been noted only recently. Work on cytomegalovirus （CMV） infection in the murine model has revealed MCs as players in a novel cross-talk axis between innate and adaptive immune surveillance of CMV, in that infection of MCs, which is associated with MC degranulation and release of the chemokine CCL5, enhances the recruitment of protective CD8 T cells to extravascular sites of virus replication, specifically to lung interstitium and alveolar epithelium. Here, we have expanded on these studies by investigating the conditions for MC activation and the consequent degranulation in response to host infection. Surprisingly, the data revealed two temporally and mechanistically distinct waves of MC activation： an almost instant indirect activation that depended on TLR3/TRIF signaling and delayed activation by direct infection of MCs that did not involve TLR3/rRIF signaling. Cell type-specific Cre-recombination that yielded eGFP-expressing reporter virus selectively originating from MCs identified MC as a new in vivo, first-hit target cell of productive murine CMV infection.

关键词： cytomegalovirus innate immunity mast cells mast cell-specific Cre-recombination TLR3FrRIF-signaling

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