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Erlotinib combination with a mitochondria-targeted ubiquinone effectively suppresses pancreatic cancer cell survival

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World Journal of Gastroenterology 2024年第7期30卷 714-726页

作者： Pui-Yin Leung Wenjing Chen Anissa n Sari Poojitha Sitaram Pui-Kei Wu Susan Tsai Jong-In Park Department of Biochemistry Medical College of WisconsinMilwaukeeWI 53226United States Department of Surgery Medical College of WisconsinMilwaukeeWI 53226United States

BACKGROUnD Pancreatic cancer is a leading cause of cancer-related *** activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug ***,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic *** previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell *** has not been tested for this *** To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell ***Δψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell *** viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive *** synergy between erlotinib and MitoQ was then analyzed using SynergyFinder *** preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line *** Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive *** triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of *** suggested that these drugs synergistically induced tumor cell *** with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each *** Our findings suggest tha

关键词： Pancreatic cancer Erlotinib Mitochondria-targeted ubiquinone Mitochondria Combination therapy

Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer's disease rat brain

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Journal of Sport and Health Science 2024年第2期13卷 245-255页

作者： Cecilie Skarstad norevik Aleksi M.Huuha Ragnhild n.RФsbjФrgen Linda Hildegard Bergersen Kamilla Jacobsen Rodrigo Miguel-dos-Santos Liv Ryan Belma Skender Jose Bianco n.Moreira Asgeir Kobro-Flatmoen Menno P.Witter nathan Scrimgeour Atefe R.Tari Cardiac Exercise Research Group(CERG) Department of Circulation and Medical ImagingNorwegian University of Science and Technology7491TrondheimNorway Department of neurology and Clinical neurophysiology St.Olavs University Hospital7030TrondheimNorway Institute of Oral Biology University of Oslo0372OsloNorway Department of Physiology Federal University of SergipeS~ao Cristov~ao49100-000SergipeBrazil Centre of Molecular Inflammation Research Department of Clinical and Molecular MedicineNorwegian University of Science and Technology7491TrondheimNorway Kavli Institute for Systems neuroscience Centre for Neural Computationand Egil and Pauline Braathen and Fred Kavli Centre for Cortical MicrocircuitsNorwegian University of Science and Technology7030TrondheimNorway K.G.Jebsen Centre for Alzheimer’s Disease Norwegian University of Science and Technology7030TrondheimNorway

Background:Exercise training promotes brain plasticity and is associated with protection against cognitive impairment and Alzheimer’s disease(AD).These beneficial effects may be partly mediated by blood-borne *** we used an in vitro model of AD to investigate effects of blood plasma from exercise-trained donors on neuronal viability,and an in vivo rat model of AD to test whether such plasma impacts cognitive function,amyloid pathology,and ***:Mouse hippocampal neuronal cells were exposed to AD-like stress using amyloid-βand treated with plasma collected from human male donors 3 h after a single bout of high-intensity *** in vivo studies,blood was collected from exercise-trained young male Wistar rats(high-intensity intervals 5 days/week for 6 weeks).Transgenic AD rats(McGill-R-Thyl-APP)were inj ected 5 times/fortnight for 6 weeks at2 months or 5 months of age with either(a)plasma from the exercise-trained rats,(b)plasma from sedentary rats,or(c)*** function,amyloid plaque pathology,and neurogenesis were *** plasma used for the treatment was analyzed for 23 ***:Plasma from exercised donors enhanced cell viability by 44.1%(p=0.032)and reduced atrophy by 50.0%(pn amyloid-β-treated *** vivo exercised plasma treatment did not alter cognitive function or amyloid plaque pathology but did increase hippocampal neurogenesis by~3 fold,regardless of pathological stage,when compared to saline-treated *** of 7 cytokines were significantly reduced in exercised plasma compared to sedentary ***:Our proof-of-concept study demonstrates that plasma from exercise-trained donors can protect neuronal cells in culture and promote adult hippocampal neurogenesis in the AD rat *** effect may be partly due to reduced pro-inflammatory signaling molecules in exercised plasma.

关键词： Cytokines High-intensity interval training Inflammation neurons Plasma transfusion

Promotion of structural plasticity in area V2 of visual cortex prevents against object recognition memory deficits in aging and Alzheimer's disease rodents

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neural Regeneration Research 2024年第8期19卷 1835-1841页

作者： Irene navarro-Lobato Mariam Masmudi-Martín Manuel F.López-Aranda Juan F.López-Téllez Gloria Delgado Pablo Granados-Durán Celia Gaona-Romero Marta Carretero-Rey Sinforiano Posadas María E.Quiros-Ortega Zafar U.Khan Laboratory of neurobiology Centro de Investigaciones Médico Sanitarias(CIMES)University of MalagaMalagaSpain Department of Medicine Faculty of MedicineUniversity of MalagaMalagaSpain Centro de Investigación Biomédica en Red de Enfermedades neurodegenerativas(CIBERnED) Institute of Health Carlos IIIMadridSpain the Donders Institute for Brain Cognition and Behaviour Radboud UniversityNijmegenThe Netherlands the Brain Metastasis Group National Cancer Research Centre(CNIO)MadridSpain the Department of neurobiology University of California-Los AngelesLos AngelesCAUSA

Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for *** till now,all potential drug candidates have failed to produce satisfa ctory ***,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of *** this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s ***,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDnF).A knockdown of BDnF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM *** findings suggest that BDnF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s ***,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.

关键词： behavioral performance brain-derived neurotrophic factor cognitive dysfunction episodic memory memory circuit activation memory deficits memory enhancement object recognition memory prevention of memory loss regulator of G protein signaling

Data-driven drug repositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

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neural Regeneration Research 2025年第7期20卷 1997-1998页

作者： Paz Cartas-Cejudo Adriana Cortés Mercedes Lachén-Montes Elena Anaya-Cubero Joaquín Fernández-Irigoyen Enrique Santamaría Clinical neuroproteomics Unit Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

Data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous *** diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual *** the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining *** last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.

关键词： diseases drug amyloid

The neglect of nonnative orthopterans as potential invaders:A call for awareness

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Insect Science 2024年第4期31卷 994-1000页

作者： Anna K.Kulessa Paride Balzani Ismael Soto Antonín Kouba David Renault Ali Serhan Tarkan Phillip J.Haubrock Ruhr University Bochum Faculty of Biology and BiotechnologyBochumGermany Faculty of Biology University of Duisburg-EssenUniversitätsstraße 5EssenGermany Faculty of Fisheries and Protection of Waters South Bohemian Research Center of Aquaculture and Biodiversity of HydrocenosesUniversity of South Bohemia in CˇeskéBudeˇjoviceVodnˇanyCzech Republic University of Rennes CNRSECOBIO(EcosystèmesBiodiversitéEvolution)UMRRennesFrance Faculty of Fisheries Department of Basic SciencesMu˘gla SıtkıKoçman UniversityMu˘glaTurkey Department of Life and Environmental Sciences Bournemouth UniversityPooleDorsetUK Faculty of Biology and Environmental Protection Department of Ecology and Vertebrate ZoologyUniversity ofŁodzŁodzPoland Department of River Ecology and Conservation Senckenberg Research Institute and Natural History Museum FrankfurtGelnhausenGermany Center for Applied Mathematics and Bioinformatics Gulf University for Science and TechnologyMubarak Al-AbdullahKuwait

Despite the potential ecological and economic impacts of invasive species,there is a dearth of data on the presence,impacts,and management implications of potentially invasive Orthoptera *** lack of research and inconsistent data,including risk screenings and impact assessments,is especially evident in ***,assessing the status,distribution,and potential threats of nonnative Orthoptera in Europe remains challenging,impeding the development of effective management *** address this gap,we call for increased efforts to collect and curate data on non-native and possibly invasive Orthoptera in *** efforts will improve our understanding of this order’s invasion dynamics,facilitate the identification of priority areas for conservation,and support the development of effective management policies and preventive measures.

关键词： costs cricket damages grasshopper impact research

Impact of STAT-signaling pathway on cancer-associated fibroblasts in colorectal cancer and its role in immunosuppression

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1705-1724页

作者： Damián Sánchez-Ramírez Mónica G Mendoza-Rodríguez Omar R Alemán Fernando A Candanedo-González Miriam Rodríguez-Sosa Juan JoséMontesinos-Montesinos Mauricio Salcedo Ismael Brito-Toledo Felipe Vaca-Paniagua Luis I Terrazas Unidad de Investigacion en Biomedicina Facultad de Estudios Superiores IztacalaUniversidad Nacional Autonoma de MexicoTlalnepantla 54090Estado de MexicoMexico Department of Biology Facultad de QuimicaUniversidad Nacional Autonoma de MexicoCiudad UniversitariaMexico City 04510Mexico Department of Pathology National Medical Center Century XXIInstituto Mexicano del Seguro SocialMexico City 06720Mexico Laboratorio de Células Troncales Mesenquimales Unidad de Investigación Médica en Enfermedades OncológicasHospital de Oncología Centro Medico Nacional Siglo XXIInstituto Mexicano del Seguro SocialMexico City 06720Mexico Unidad de Investigacion en Biomedicina y Oncologia Genomica Instituto Mexciano del Seguro SocialMexico City 07300Mexico Servicio de Colon y Recto Hospital de Oncología Centro Medico Nacional Siglo XXIInstituto Mexicano del Seguro SocialMexico City 06720Mexico Laboratorio nacional en Salud Facultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla 54090Estado de MexicoMexico

Colorectal cancer(CRC)remains one of the most commonly diagnosed and deadliest types of cancer *** displays a desmoplastic reaction(DR)that has been inversely associated with poor prognosis;less DR is associated with a better *** reaction generates excessive connective tissue,in which cancer-associated fibroblasts(CAFs)are critical cells that form a part of the tumor *** are directly involved in tumorigenesis through different ***,their role in immunosuppression in CRC is not well understood,and the precise role of signal transducers and activators of transcription(STATs)in mediating CAF activity in CRC remains *** the myriad chemical and biological factors that affect CAFs,different cytokines mediate their function by activating STAT signaling ***,the harmful effects of CAFs in favoring tumor growth and invasion may be modulated using STAT ***,we analyze the impact of different STATs on CAF activity and their immunoregulatory role.

关键词： Cancer-associated fibroblasts Signal transducer and activator of transcription signaling Colorectal cancer Immunity Immunosuppression

Organ Abscission in Plants: With Special Emphasis on Bell Pepper

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Phyton-International Journal of Experimental Botany 2024年第7期93卷 1467-1484页

作者： Ramiro Reyes-Castro Héctor G.núñez-Palenius Juan I.Valiente-Banuet María E.Sosa-Morales Blanca E.Orosco-Alcalá Rafael Guzmán-Mendoza Graciela M.L.Ruiz-Aguilar Rogelio Costilla-Salazar Life Sciences Division Universidad de GuanajuatoIrapuato36500México School of Engineering and Sciences Tecnologico de MonterreyQuerétaro76130México

Bell pepper(Capsicum annuum L.),along with potato and tomato,is one of the three most cultivated vegetables in the *** pepper is worldwide accepted due to its characteristics of color,smell,ﬂavor,and *** pepper is also considered a nutritious food due to its vitamin and antioxidant *** Mexico,bell pepper production has a high value because it is grown for the international markets,particularly the United States of ***,the abscission ofﬂowers and fruits is a factor that limits the yield,hinders the planning of activities,and causes a variation in the prices of *** to the importance of this process,in this work we did a bibliometric analysis and literature review of scientiﬁc advances for the understanding of the abscission pro-cess in plants,and in particular for the bell ***,we introduce new perspectives that would help direct future research about organ abscission in ***,the lack of research that would further clarify abscis-sion process in the bell pepper plant is discussed.

关键词： Capsicum annuum abscission zone plant growth regulators environmental factors

Cytoplasmic DnA: sources, sensing, and role in aging and disease

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四川生理科学杂志 2024年第4期46卷 89-89页

作者： Karl n Miller Aging Cancer and Immuno-oncology Program Sanford Burnham Prebys Medical Discovery Institute La Jolla CA 92037 USA Department of Physiology and Biomedical Engineering Mayo Clinic Rochester MN 55905 USA

Endogenous cytoplasmic DnA(cytoDnA)species are emerging as key mediators of inflammation in diverse physiological and pathological *** the role of endogenous cytoDnA in innate immune activation is well established,the cytoDnA species themselves are often poorly characterized and difficult to distinguish,and their mechanisms of formation,scope of function and contribution to disease are incompletely understood.

关键词： endogenous inflammation incomplete

Civil Ambassador Enriches Peru-China Relations

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China news Release 2024年第2期 54-57页

作者： Rubén Tang the Pontificia Catholic University of Peruand Asian Academic Institutions

Peru and China are both ancient countries with rich histories and *** immigration to Peru is the most significant in Latin *** first Chinese immigrants arrived in Peru in 1849 to seek a new future in these distant *** initially worked in the fields and later established successful businesses,making important contributions to the country's development across various sectors.

关键词： initially Latin Per