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Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism:WLB-73502,an analgesic with improved efficacy and safety profile compared to strong opioids

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Acta Pharmaceutica Sinica B 2023年第1期13卷 82-99页

作者： Alba Vidal-Torres Begoña Fernández-Pastor Mónica García Eva Ayet Anna Cabot Javier Burgueño Xavier Monroy Bertrand Aubel Xavier Codony Luz Romero Rosalía Pascual maria Teresa Serafini Gregorio Encina carmen Almansa Daniel Zamanillo Manuel Merlos JoséMiguel Vela WeLab Barcelona Parc Cientific de BarcelonaBarcelona 08028Spain

Opioids are the most effective painkillers,but their benefit-risk balance often hinder their therapeutic ***-73502 is a dual,bispecific compound that binds sigma-1(S1R)and mu-opioid(MOR)***-73502 is an antagonist at the *** behaved as a partial MOR agonist at the G-protein pathway and produced no/unsignificantβ-arrestin-2 recruitment,thus demonstrating low intrinsic efficacy on MOR at both signalling *** its partial MOR agonism,WLB-73502exerted full antinociceptive efficacy,with potency superior to morphine and similar to oxycodone against nociceptive,inflammatory and osteoarthritis pain,and superior to both morphine and oxycodone against neuropathic ***-73502 crosses the blood-brain barrier and binds brain S1R and MOR to an extent consistent with its antinociceptive *** to morphine and oxycodone,tolerance to its antinociceptive effect did not develop after repeated 4-week ***,contrary to opioid comparators,WLB-73502 did not inhibit gastrointestinal transit or respiratory function in rats at doses inducing full efficacy,and it was devoid of proemetic effect(retching and vomiting)in ferrets at potentially effective ***-73502 benefits from its bivalent S1R antagonist and partial MOR agonist nature to provide an improved antinociceptive and safety profile respect to strong opioid therapy.

关键词： WLB-73502 Sigma-1 receptor Mu-opioid receptor Biased agonist Analgesic activity Chronic pain Neuropathic pain Safety

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Ginger infusion increases diet-induced thermogenesis in healthy individuals:A randomized crossover trial

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Food Bioscience 2022年第6期50卷 314-319页

作者： Ana Paula da Costa Soares Natália Cristina de Faria Guilherme Fonseca Graciano James Almada da Silva Vitoria Shievila dos Santos Gonçalves Virginia Del carmen Trancoso Valenzuela maria Isabel Toulson Davisson Correia Lucilene Rezende Anastácio Post-Graduate Program in Food Science Pharmacy SchoolUniversidade Federal de Minas GeraisBrazil Surgical Post-Graduate Program Alfa Institute of GastroenterologyHospital das ClínicasUniversidade Federal de Minas GeraisBrazil Pharmacy Department Universidade Federal de SergipeBrazil Fundação Ezequiel Dias Brazil

The purpose of this study is to evaluate the acute effect of ingesting ginger infusion on energy metabolism,appetite responses,and food intake in healthy *** is a clinical(RBR-9ZJGQM),randomized,open,and crossover study with a minimum interval of seven days between *** drinks,ginger infusion(2 g)and water(control)were served with a standard *** has 21 volunteers of both sexes(18–40 years old,18.5–26 kg/m2).Consumption of ginger tea increased on average 95.5±27.4 kcal/day the non-nitrogen energy expenditure after 240 min of ingestion(p=0.002).There was a significant effect of ginger on diet-induced thermogenesis(difference between ginger tea treatment ***:113.0±43.0 kcal/day,p=0.016).However,appetitive responses and prospective food intake did not differ between ginger tea and water intake.

关键词： Zingiber officinale Ginger Indirect calorimetry Energy metabolism

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Myxoid Meningioma:An Example of a Rare Brain Tumour of Difficult Diagnosis

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Open Journal of Pathology 2013年第1期3卷 51-53页

作者： Javier Ortiz maria Dolores Ludena Jesus Goncalves Sofia Del carmen Angel Maillo Agustin Bullon Pathology Department Hospital Universitario de Salamanca(Complejo Hospitalario de Salamanca)SalamancaSpain Neuro-surgery Department Hospital Virgen de la Vega(Complejo Hospitalario de Salamanca)SalamancaSpain

We present a case of a Myxoid Meningioma noticed in a 43-year-old woman. The patient, who had no noteworthy medical antecedents, showed repeated focal epileptic crisis. Imaging studies (MR and CT) showed a solitary and well delimited tumour located in the frontral lobe. Once extirpated, the histological study revealed a neoplasm of myxoid and benign appearance, with elongated and uniform cells, with no atypias and a very low mitotic index. Immunohistochemisty studies (positivity for Vimentin and Epithelial Membrane Antigen, and negativity for the other markers) as well as physical and radiological examination of the patient (absence of tumours in any other location), suggested the diagnosis of a Myxoid Meningioma, which was confirmed by electron microscopy (by the presence of desmosomes). We also revise the characteristics of Myxoid Meningiomas, an absolutely exceptional primary tumour of the central nervous system.

关键词： Myxoid Meningioma Immunohistochemistry Electron Microscopy

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Effects of 50 Percent Substitution of Soybean Meal by Alternative Proteins from <i>Hermetia illucens</i>or Spirulina platensis in Meat-Type Chicken Diets with Graded Amino Acid Supply

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Open Journal of Animal Sciences 2018年第2期8卷 119-136页

作者： Susanne Velten carmen Neumann Martina Bleyer Eva Gruber-Dujardin maria Hanuszewska Barbara Przybylska-Gornowicz Frank Liebert Department of Animal Sciences Division Animal Nutrition Physiology Georg-August-University of Goettingen Goettingen Germany German Primate Center GmbH Pathology Unit Goettingen Germany Department of Poultry Science University of Warmia and Mazury in Olsztyn Olsztyn Poland Department of Histology and Embryology Faculty of Veterinary Medicine University of Warmia and Mazury in Olsztyn Olsztyn Poland

Alternative protein sources, such as insects or algae meals are in special focus of animal nutrition in order to replace soybean meal (SBM). As part of the multidisciplinary project “sustainability transitions” this study evaluated effects of replacing SBM by partly defatted larvae meal from the black soldier fly, Hermetia illucens or meal from the micro algae Spirulina platensis in broiler diets. The aim of the current study was to investigate the chickens’ growth performance and the intestinal morphology as well as the health status. 288 one-day-old male growing chickens (Ross 308) from a commercial hatchery were randomly allotted to 48 pens (6 birds per pen) for the growth study with five diets and feed supply on free choice level. The control diet was based on wheat, corn and SBM. The experimental diets replaced 50% of SBM by the alternative proteins under study, both on a basic level of amino acid (AA) supplementation (Lys and Met added equal to the control diet) (diet HM and SM) and an extended level of AA fortification (Lys, Met, Thr, Arg, Val added) (diet HM+ and SM+). Response of chickens was evaluated by zoo-technical parameters, which were under weekly control (e.g. growth, feed intake, feed conversion ratio, mortality). After finishing the growth study birds from control and the experimental diets at the basic level of AA supplementation were slaughtered after 12 hour fastening and utilized for gut morphometric analysis and histological evaluation of the health status. Diets at a basic level of AA fortification led to significant depression of growth, feed intake, feed conversion ratio, and protein conversion ratio, respectively. In addition, the acceptance of the Spirulina diet was lower (p ≤ 0.001) as compared to the Hermetia based diet. However, the extended level of AA supplementation improved all parameters significantly. Diets without extended AA supply altered some morphological parameters of the intestinal wall, but the nutritional significance o

关键词： Growing Chickens Feed Growth Performance Histology Morphometry Spirulina platensis Hermetia illucens

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Multi-omic study to unmask genes involved in prostate cancer development in amulti-case family

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Cancer Communications 2024年第3期44卷 443-447页

作者： Lucia Chica-Redecillas Sergio Cuenca-Lopez Eduardo Andres-Leon Laura carmen Terron-Camero Blanca Cano-Gutierrez Jose Manuel Cozar Jose Antonio Lorente Fernando Vazquez-Alonso Luis Javier Martinez-Gonzalez maria Jesus Alvarez-Cubero GENYO Centre for Genomics and Oncological ResearchPfizerUniversity of GranadaAndalusian Regional GovernmentPTS GranadaGranadaGranadaSpain Department of Biochemistry Molecular Biology III and ImmunologyFaculty of MedicineUniversity of GranadaPTS GranadaGranadaGranadaSpain Bioinformatics Unit Institute of Parasitology and Biomedicine“López-Neyra”Spanish National Research CouncilGranadaGranadaSpain Nursery Service.University Hospital Clínico San Cecilio GranadaGranadaSpain Urology Department University Hospital Virgen de las NievesGranadaGranadaSpain Legal Medicine and Toxicology Department Faculty of MedicineUniversity of GranadaPTS GranadaGranadaGranadaSpain Ibs Biosanitary Research InstituteGranadaGranadaSpain

Dear Editor,Hereditary prostate cancer(PC)comprises 5%-10%of all PC *** increased risk of PC in menwith a family his-tory of the disease is well known and is commonly caused by germline mutations,leading to clinical guidelines men-tioning various genes for identifying high-risk ***,the complex inheritance patterns involvingmul-tiple single nucleotide polymorphisms(SNPs)make it a genetically heterogeneous disease,with genetic testing still in its early stages.

关键词： cancer clinical cases

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Platelet Indices in Patients with Acute Coronary Syndrome

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Journal of Biosciences and Medicines 2015年第11期3卷 71-76页

作者： Silvia Cristina Costa carmen Guilherme de Matos Vinagre Ana Paula Marte Chacra maria Regina Andrade de Azevedo Department of Health Sciences University of Santo Amaro Sao Paulo Brazil Department of Cardiology Heart Institute University of Sao Paulo Sao Paulo Brazil

The platelet indices Mean Platelet Volume (MPV), Platelet Distribution Width (PDW) and Plate-letcrit (PCT) provided by automated hematology analysis are rarely used in clinical practice. Platelets play a central role in the pathogenesis of acute coronary syndromes (ACS) and high MPV has been associated to more reactive platelets and regarded as an independent risk factor for myocardial infarction. In this study, platelet indices were evaluated in 39 patients with ACS presenting two altered biochemical parameters, C reactive protein (CRP) and creatine kinase fraction MB (CK-MB). The results obtained showed significantly higher MPV and PDW values in the group with ACS in comparison to the control group. Also observed was a weak but significant positive correlation between MPV and CK-MB. In view of findings of previous studies, which have associated macroplatelets with higher thrombotic potential our results suggest that the use of the MPV and PDW indices as additional and complementary markers may contribute to the investigation and follow-up of thrombotic risk in patients with ACS.

关键词： Platelets Platelet Indices Acute Coronary Syndrome CK-MB

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Aggregation properties of a therapeutic peptide for rheumatoid arthritis:A spectroscopic and molecular dynamics study

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ChemPhysMater 2022年第1期1卷 62-70页

作者： Rita Cimino Marco Savioli Noemi Ferrante Carrante Ernesto Placidi Hilda Garay-Perez Matilde López-Abad Alexis Musacchio Lasa maria Del carmen Domínguez-Horta Emanuela Gatto Francesca Cavalieri Gianfranco Bocchinfuso mariano Venanzi PEPSA-LAB Department of Chemical Sciences and TechnologyUniversity of Rome Tor VergataVia della Ricerca Scientifica 100133RomeItaly Department of Physics University of Rome‘Sapienza’P.le A.Moro 500185 RomeItaly Centre for Genetic Engineering and Biotechnology PO Box 616210600HavanaCuba School of Science RMIT UniversityMelbourneVIC 3001Australia

The biological properties of therapeutic peptides,such as their pharmacokinetics and pharmacodynamics,are correlated with their structure and aggregation ***,we studied the aggregation properties of a therapeutic peptide(CIGB-814),currently in phase 2 clinical trial,for the treatment of rheumatoid arthritis over a wide range of concentrations(μM-mM).We applied spectroscopic techniques(fluorescence,circular dichro-ism,resonance,and dynamic light scattering),atomic force microscopy,and molecular dynamics simulations to determine the aggregation mechanism of *** found that the hierarchical aggregation of CIGB-814 at micromolar concentrations was initiated by the formation of peptide ***,the peptide oligomers trigger the nucleation and growth of peptide nanostructures(cac=123μM),ultimately leading to the fibrillization of CIGB-814(cac’=508μM).These results pave the way for a deeper understanding of the CIGB-814 therapeutic activity and may give important insights on its pharmacokinetics.

关键词： Molecular dynamics of peptide oligomers Peptide aggregation Peptide fibrils Peptide nanostructures Therapeutic peptides Treatment of rheumatoid arthritis

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中国与厄瓜多尔石油贸易简析

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商场现代化 2010年第31期 4-5页

作者： maria DEL carmen MARIN TOVAR 上海大学

一、导言厄瓜多尔的经济基础是主要满足国内需求的石油产品以及供国内消费和出口的农产品。2008年，原油与精炼石油产品占出口收入的63％。

关键词：石油产品厄瓜多尔易简中国国内需求出口收入 2008年经济基础

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Titanium dioxide induced inflammation in the small intestine

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World Journal of Gastroenterology 2012年第34期18卷 4729-4735页

作者： Carolina Maciel Nogueira Walter Mendes de Azevedo maria Lucia Zaidan Dagli Sérgio Hiroshi Toma AndréZonetti de Arruda Leite maria Laura Lordello Iêda Nishitokukado carmen Lúcia Ortiz-Agostinho maria IrmaSeixas Duarte Marcelo Alves Ferreira Aytan Miranda Sipahi Department of Gastroenterology Laboratory of Clinical and Experimental Gastroen-terologySchool of MedicineUniversity of So PauloCerqueira César01246-900 So PauloBrazil Department of Fundamental Chemistry Federal University of PernambucoCidade Universitária50670-901 RecifeBrazil Department of Pathology Veterinary Medicine SchoolUniversity of So PauloCidade Universitária05508-270 So PauloBrazil Laboratory of Supramolecular Chemistry and Nanotechnology Chemistry InstituteUniversity of So PauloCidade Universitária05513-970 So PauloBrazil Laboratory of Transmissible Disease Medicine SchoolUniversity of So PauloCerqueira César01246-900 So PauloBrazil Laboratory of Cellular Biology Medicine SchoolUniversity of So PauloCerqueira César01246-900 So PauloBrazil

AIM:To investigate the effects of titanium dioxide (TiO2) nanoparticles (NPTiO 2 ) and microparticles (MPTiO 2 ) on the inflammatory response in the small intestine of mice. METHODS: Bl 57/6 male mice received distilled water suspensions containing TiO 2 (100 mg/kg body weight) as NPTiO 2 (66 nm), or MPTiO 2 (260 nm) by gavage for 10 d, once a day; the control group received only distilled water. At the end of the treatment the duodenum, jejunum and ileum were extracted for assessment of cytokines, inflammatory cells and titanium content. The cytokines interleukin (IL)-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-23, tumor necrosis factor-α (TNF-α), intracellular interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) were evaluated by enzyme-linked immunosorbent assay in segments of jejunum and ileum (mucosa and underlying muscular tissue). CD4 + and CD8 + T cells, natural killer cells, and dendritic cells were evaluated in duodenum, jejunum and ileum samples fixed in 10% formalin by immuno-histochemistry. The titanium content was determined by inductively coupled plasma atomic emission spectrometry. RESULTS: We found increased levels of T CD4 + cells (cells/mm 2 ) in duodenum:NP 1240 ± 139.4, MP 1070 ± 154.7 vs 458 ± 50.39 (P < 0.01); jejunum:NP 908.4 ± 130.3, MP 813.8 ± 103.8 vs 526.6 ± 61.43 (P < 0.05); and ileum:NP 818.60 ± 123.0, MP 640.1 ± 32.75 vs 466.9 ± 22.4 (P < 0.05). In comparison to the control group, the groups receiving TiO 2 showed a statistically significant increase in the levels of the inflammatory cytokines IL-12, IL-4, IL-23, TNF-α, IFN-γ and TGF-β. The cytokine production was more pronounced in the ileum (mean ± SE):IL-12: NP 33.98 ± 11.76, MP 74.11 ± 25.65 vs 19.06 ± 3.92 (P < 0.05); IL-4: NP 17.36 ± 9.96, MP 22.94 ± 7.47 vs 2.19 ± 0.65 (P < 0.05); IL-23: NP 157.20 ± 75.80, MP 134.50 ± 38.31 vs 22.34 ± 5.81 (P < 0.05); TNFα: NP 3.71 ± 1.33, MP 5.44 ± 1.67 vs 0.99± 019 (P < 0.05); IFNγ: NP 15.85 ± 9.99, MP 34.08 ± 11.44 vs 2.81 ±

关键词： Titanium dioxide Microparticles Nanopar-tides Immune response Small intestine Mice

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Aggressive Angiomyxoma: An Unusual Female Pelvic Tumour. Report of Three Cases and Review of the Literature

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Surgical Science 2010年第2期1卷 40-45页

作者： Juan Antonio Martin-Cartes Manuel Bustos-Jimenez maria Jesus Tamayo-Lopez maria del carmen Palacios-Gonzalez Virginia Gomez-Cabeza de Vaca Antonio Muñoz Ortega Division of Surgery Abdominal Wall Surgery UnitSevilleSpain

Aggressive angiomyxoma was first described in 1983 by Steeper and Rosai, and fewer than 150 cases have been reported in the world medical literature. It is a soft-tissue tumour of the pelvis and perineum. The recurrence rate is high, and often extensive resections are performed with considerable morbidity. These tumours are benign, locally infiltrative mesenchymal neoplasms with a predilection for the female pelvis and perineum and they usually tend to recur. Furthermore, these tumours often reach too large dimensions before becoming clinically symptomatic;their incidence is higher in women of the reproductive age group;however a few cases of its occurrence outside the pelvis have also been reported. In this study, we reported three cases with aggressive pelvic angiomyxoma treated with surgical methods and used an approach that described by Kraske in order to get access to lower rectal cancers. Accurate preoperative diagnosis should alert the surgeon to the need for wide excision, which is essential for prevention of local recurrence.

关键词： Aggressive Angiomyxoma Soft Tissue Tumour Perineum and Pelvis Tumour

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