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Biological Activity of N-Hydroxyethyl-4-aza-2,3-didehydropodophyllotoxin Derivatives upon Colorectal Adenocarcinoma Cells

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Open Journal of Medicinal Chemistry 2014年第1期4卷 1-11页

作者： Christian Vélez beatriz zayas Ajay Kumar Universidad Metropolitana School of Environmental Affairs San Juan Puerto Rico USA

Etoposide is a chemotherapy drug derived from the natural lignin podophyllotoxin. Our novel generated Aza-podophyllotoxin compounds (AZP 8a & AZP 9a) are analogues of podophyllotoxin and were previously screened for anti-cancer activity through the NCI 60 cell line screening panel showing activity on various cell types including colon cancer. This study expands the toxicological screening by studying apoptosis and various hallmark events as part of the mechanism of action of these compounds on colon cancer cells. The COLO 205 cell line was selected and exposed to AZP to determine the IC50 doses at 24 hours treatment. Apoptosis hallmark events such as migration of phosphatidylserine (PS) to the cell membrane, DNA fragmentation, cell cycle effects, mitochondrial membrane permeabilization and caspase activation were included. Experiments were performed in triplicates for all tested compounds including AZP 8a, AZP 9a, camptothecin as positive control and vehicle as negative control. Our results present contrasting apoptotic activity between the experimental compounds. Compound 8a presented migration of PS (annexin V assay), DNA fragmentation and cell cycle arrest at S phase. Compound 9a presented PS migration with fragmented DNA, cell cycle arrest at S phase, mitochondrial membrane permeabilization and activation of caspase 3, 8 and 9. Compound 8a without the oxygen atoms in ring A appears to cause effects similarly to autophagy as induced by etoposide, a cancer drug analogue of our heterocyclic compounds. Compound 9a with the oxygen atoms in expanded ring A presented induction of cell death following activation of a classical apoptosis pathway. Our results suggest that minor structural differences among these AZP can account for the difference in biological response and cancer cell toxicity.

关键词： Etoposide Podophyllotoxin Aza-Podophyllotoxin Colon Cancer COLO 205

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Cell Death Effects of the Phthalate 2-Ethyl-1-Hexanol on Human Linfoblast Cells

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Open Journal of Apoptosis 2019年第1期8卷 1-15页

作者： Karoline Rios Christian Vélez beatriz zayas School of Science and Technology and Environment Universidad Ana G. Méndez San Juan Puerto Rico

Phthalates have been used in a wide variety of consumer goods. Their versatility as plasticizers has translated into worldwide use in a vast array of consumer products. These compounds can leach into matrices, such as food and liquids that can be routed for human exposure. One of the most used phthalates is Diethylhexyl phthalate (DEHP). Diethylhexyl phthalate and its metabolite 2-ethyl-1-hexanol (2-EH) have demonstrated biological effects which merit further evaluation. In this work, we expand on our previous work with DEHP and screen the 2-EH metabolite for different cell death endpoints such as growth inhibition, apoptosis, autophagy, caspase activation, DNA fragmentation, and cell cycle arrest using fluorophores and the NC3000 instrument. Significant results (p 0.05) revealed higher toxicity for the 2-EH metabolite when compared to DEHP. Also, 2-EH presented apoptosis induction with characteristic hallmarks, such as loss of mitochondrial membrane potential, caspase activation, DNA fragmentation and cell cycle arrest at the S phase. In addition, the presence of autophagosome was detected through L3CB protein staining. We conclude that 2-EH presents differences in cell death endpoints that interestingly differ from the DEHP parent compound. Further studies are needed to establish the molecular pathways responsible for the observed effects.

关键词： Phthalates 2-Ethyl-1-Hexanol Diethylhexyl Phthalate Autophagy Apoptosis Lymphoblast Caspase

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Novel Nitrobenzazolo[3,2-a]quinolinium Salts Induce Cell Death through a Mechanism Involving DNA Damage, Cell Cycle Changes, and Mitochondrial Permeabilization

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Open Journal of Apoptosis 2013年第2期2卷 13-22页

作者： Christian Vélez Osvaldo Cox Carlos A. Rosado-Berrios Dennise Molina Luz Arroyo Sujey Carro Anton Filikov Vineet Kumar Sanjay V. Malhotra Marisol Cordero beatriz zayas Arkansas State University Jonesboro USA Laboratory of Synthetic Chemistry-SAIC Frederick National Laboratory for Cancer Research Frederick USA Universidad Metropolitana Caracas Venezuela Universidad Metropolitana San Juan Puerto Rico University of Puerto Rico San Juan USA

This study reports the capacity of three nitro substituted benzazolo[3,2-a]quinolinium salts NBQs: NBQ 95 (NSC-763304), NBQ 38 (NSC 763305), and NBQ 97 (NSC-763306) as potential antitumor agents. NBQ’s are unnatural alkaloids possessing a positive charge that could facilitate interaction with cell organelles. The anticancer activities of these compounds were evaluated through the National Cancer Institute (NCI) 60 cell line screening which represents diverse histologies. The screening was performed at 10 μM on all cell lines. Results from the NCI screening indicated cytotoxicity activity on six cell lines. In order to explore a possible mechanism of action, a detailed biological activity study of NBQ 95 and NBQ 38 was performed on A431 human epidermoid carcinoma cells to determine an apoptotic pathway involving, cell cycle changes, DNA fragmentation, mutations, mitochondrial membrane permeabilization and caspases activation. DNA fragmentation, cell cycle effects, mutagenesis, mitochondrial permeabilization and activation of caspases were determined by fluorimetry and differential imaging. Our data showed that A431 growth was inhibited with an average IC50 of 30 mM. In terms of the mechanism, these compounds interacted with DNA causing fragmentation and cell cycle arrest at sub G0/G1 stage. Mutagenesis was higher for NBQ 38 and moderate for NBQ 95 Mitochondrial permeabilization was observed with NBQ 38 and slightly for NBQ 95. Both compounds caused activation of Caspases 3 and 7 suggesting an apoptotic cell death pathway through an intrinsic mechanism. This study reports evidence of the toxicity of these novel compounds with overlapping structural and mechanistic similarities to ellipticine, a known anti-tumor compound.

关键词： Apoptosis A431 Quinolinium Salts Mutagenesis Caspase Activation

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Oligodendroctyes:the forgotten players of diabetes pathophysiology

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Neural Regeneration Research 2024年第11期19卷 2349-2350页

作者： Juan Antonio López-Villodres beatriz García-Díaz Departamento Fisiología Humana Histología HumanaAnatomía Patológica y Educación Física y DeportivaFacultad de MedicinaUniversidad de MálagaMálagaSpain UGC Neurociencia.Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina(IBIMA Plataforma Bionand) MálagaSpain

Oligodendrocytes(OLs),glial cells that provide myelin sheaths to axons in the central nervous system(CNS),have a dual ***,this myelin fatty cover around the axons protects the nerves and is crucial for the saltatory propagation of action *** and not less important,OLs provide trophic support to neurons and ***,OL metabolism is important for OL well-being and the proper accomplishment of their functions,and OL metabolism energetics directly affect the energy metabolism of neighboring neurons.

关键词： metabolism nerves myelin

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Generation of lossy mode resonances(LMR)using perovskite nanofilms

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Opto-Electronic Advances 2024年第2期7卷 33-40页

作者： Dayron Armas Ignacio R.Matias M.Carmen Lopez-Gonzalez Carlos Ruiz Zamarreño Pablo Zubiate Ignacio del Villar beatriz Romero Electrical Electronic and Communications Engineering DepartmentPublic University of NavarraPamplona 31006Spain Institute of Smart Cities(ISC) Public University of NavarraPamplona 31006Spain Experimental Science and Technology School Rey Juan Carlos UniversityMostoles 28933Spain

The results presented here show for the first time the experimental demonstration of the fabrication of lossy mode resonance(LMR) devices based on perovskite coatings deposited on planar waveguides. Perovskite thin films have been obtained by means of the spin coating technique and their presence was confirmed by ellipsometry, scanning electron microscopy, and X-ray diffraction testing. The LMRs can be generated in a wide wavelength range and the experimental results agree with the theoretical simulations. Overall, this study highlights the potential of perovskite thin films for the development of novel LMR-based devices that can be used for environmental monitoring, industrial sensing, and gas detection, among other applications.

关键词： perovskite thin films slab waveguide lossy mode resonance

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From Rejection to Embracement:The Catholic Perception of Spiritism in Brazil

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Cultural and Religious Studies 2024年第4期12卷 224-233页

作者： beatriz Francisco Sandrim Tamkang University Taiwan

The history of the relationship between Spiritism and Catholicism in Brazil can be traced through pivotal moments in the trajectory of the First Republic and the religious field since the 19th century,reflecting Brazil’s evolution into a modern,urban,and industrial *** to Brazil in the 1880s,Spiritism initially faced severe opposition from the Catholic Church,being dismissed as superstition and demon worship due to its engagement with death and *** Christianity,Spiritism denies the divinity of Jesus,the resurrection,and the sanctity of Church sacraments,viewing demons and angels merely as disembodied souls at different spiritual *** perceptions were further complicated by the mixing of Spiritism with African and indigenous rites,which led critics to associate it with madness and mental health ***,the relationship between Catholicism and Spiritism in Brazil has evolved positively,particularly following the popularization of Spiritism by figures like Chico *** Brazilian society,characterized by increased education and religious syncretism,has grown more tolerant of diverse practices and beliefs,diminishing historical prejudices against *** qualitative study,drawing on scholarly research and first-hand interviews,reveals that Spiritism's acceptance among Brazilian Catholics is due to its convergence with contemporary social values and the evolving profile of the average *** possessing a religion-like character,Spiritism is seen less as a distinct religion and more as a complementary set of practices and beliefs that enhance Catholic *** phenomenon mirrors the integration of Agama Hindu practices,reinforcing rather than undermining traditional religious identities.

关键词： spiritism Brazilian Catholicism religious syncretism

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Breaking paradigms: Long non-coding RNAs forming gene fusions with potential implications in cancer

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Genes & Diseases 2024年第3期11卷 311-323页

作者： David Sanchez-Marin Macrina beatriz Silva-Cazares Fany Iris Porras-Reyes Rebeca Garcia-Roman Alma D.Campos-Parra Posgrado en Ciencias Biologicas Facultad de MedicinaUniversidad Nacional Autonoma de MexicoCiudad de MexicoC.P.04360Mexico Unidad Academica Multidisciplinaria Region Altiplano Universidad Autonoma de San Luis Potost(UASLP)Carretera a Cedral Km 5+600Ejido San Jose de la TrojesMatehualaSan Luis PotosiC.P.78760Mexico Servicio de Anatomia Patologica Instituto Nacional de Cancerologia(INCan)Nino JesuisTlalpanCiudaddeMexicoC.P.14080Mexico Instituto de Salud Publica Universidad Veracruzana(UV)Av.Dr LuisDr.Castelazo Ayala s/nCol.Industrial AnimasXalapaVeracruzC.P.91190Mexico

Long non-coding RNAs(lncRNAs)are non-coding RNAs longer than 200 nucleotides with dynamic regulatory *** interact with a wide range of molecules such as DNA,RNA,and proteins to modulate diverse cellular functions through several mechanisms and,if deregulated,they can lead to cancer development and ***,it has been described that IncRNAs are susceptible to form gene fusions with mRNAs or other IncRNAs,breaking the paradigm of gene fusions consisting mainly of protein-coding ***,their biological significance in the tumor phenotype is still ***,their recent identification opens a new line of research to study their biological role in tumor-igenesis,and their potential as biomarkers with clinical relevance or as therapeutic *** present study aimed to review the IncRNA fusions identified so far and to know which of them have been associated with a potential *** address the current challenges to deepen their study as well as the reasons why they represent a future therapeutic window incancer.

关键词： Cancer Genefusions IncRNAs ncRNAs Therapy

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The dorsal root ganglion as a target for neurorestoration in neuropathic pain

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Neural Regeneration Research 2024年第2期19卷 296-301页

作者： Guillermo Estivill-Torrús Ana Belen Martínez-Padilla Lourdes Sánchez-Salido Anne Baron-Van Evercooren beatriz García-Díaz Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina(IBIMA Plataforma BIONAND) MálagaSpain Unidad Clínica de Neurociencias Hospital Regional Universitario de MálagaMálagaSpain Departamento de Biología Molecular y Bioquímica Universidad de MálagaSpain Sorbonne Université Institut du Cerveau-Paris Brain Institute-ICMINSERMCNRSAP-HPHôpital Pitié-SalpêtrièreParisFrance

Neuropathic pain is a severe and chronic condition widely found in the general *** reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in *** the processing of pain,the dorsal root ganglia constitute an important region where dorsal root ganglion neurons play a crucial role in the transmission and propagation of sensory electrical ***,the dorsal root ganglia have recently exhibited a regenerative capacity that should not be neglected in the understanding of the development and resolution of neuropathic pain and in the elucidation of innovative ***,we will review the complex interplay between cells(satellite glial cells and inflammatory cells)and factors(cytokines,neurotrophic factors and genetic factors)that takes place within the dorsal root ganglia and accounts for the generation of the aberrant excitation of primary sensory neurons occurring in neuropathic *** importantly,we will summarize an updated view of the current pharmacologic and nonpharmacologic therapies targeting the dorsal root ganglia for the treatment of neuropathic pain.

关键词： cytokines dorsal root ganglia genetic factors neuropathic pain neurotrophic factors pharmacologic and nonpharmacologic therapies satellite glial cells sensory neurons

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Lesser kestrels of the same colony do not overwinter together

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Current Zoology 2024年第4期70卷 505-512页

作者： Jorge Garcia-Macia Munir Chaouni Sara Morollon Javier Bustamante Lina Lopez-Ricaurte Juan Martinez-Dalmau beatriz Rodriguez-Moreno Vicente Urios Grupo de Investigacion Zoologia de Vertebrados Universidad de AlicanteApdo.99E-03080 AlicanteSpain Department of Wetland Ecology Estacion Biologica de Donana(CSIC)C/Americo Vespucio 2641092SevillaSpain GREFA C/MontedelPilarS/NE-28220MajadahondaMadridSpain

Migratory connectivity describes the linkage between breeding and nonbreeding sites,having major ecological implications in birds:1 season influence the success of an individual or a population in the following *** studies on migratory connectivity have used large-scale approaches,often considering regional populations,but fine-scale studies are also necessary to understand colony *** lesser kestrel Falco naumanni,an insectivorous migratory raptor which form colonies during the breeding period,was considered to have strong connectivity based on regional ***,no small-scale studies on migratory connectivity have been ***,we GPS(Global Positioning System)-tracked 40 adult lesser kestrels from 15 different Spanish breeding colonies,estimating the overlap index between home ranges and the distance between their *** was found that lesser kestrels from the same breeding colony placed their nonbreeding areas at 347±281 km(mean±standard deviation)away from each other(range=23-990),and their home ranges over-lapped by 38.4±23.6%.No differences between intra-colony and inter-colony metrics were found,which suggests that lesser kestrels from the same breeding cluster do not overwinter together,but they spread out and mixed independently of the colony belonging throughout the nonbreeding range of the ***,this study highlights the importance of performing connectivity studies using fine-scale approaches.

关键词： Falco naumanni GPS telemetry migratory connectivity nonbreeding raptor spatial ecology wintering.

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Bloom-forming cyanobacteria and dinoflagellates in five Argentinian reservoirs:Multi-year sampling

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Water Biology and Security 2024年第1期3卷 28-36页

作者： Florencia Soledad Alvarez Dalinger Borja Claudia Nidia Veronica Laura Lozano Liliana beatriz Morana María Monica Salusso Facultad de Ciencias Naturales Universidad Nacional de SaltaAvenida Bolivia 5150Salta4400Argentina Consejo Nacional de Investigaciones Científicas y T'ecnicas(CONICET) Godoy Cruz 2290Ciudad Autonoma de Buenos AiresArgentina

Harmful algal blooms are important threats to reservoir *** a 15-year period,we sampled five Argentinian reservoirs to identify the responsible species for harmful algal blooms and determine the water quality factors driving their *** reservoirs exhibit diverse morphological and hydrological characteristics and are distributed across varying climatic *** blooms included an array of species,including toxin producers such as Raphidiopsis raciborskii,Aphanizomenon gracile,and Microcystis *** contrast,dinoflagellate blooms were predominantly characterized by *** cyanobacterial blooms primarily occurred in the shallower reservoirs located in warmer regions,whereas dinoflagellate blooms occurred where temperatures were *** most intense blooms occurred during the summer,and although cyanobacterial and chlorophyte blooms co-occurred,they never coexisted with dinoflagellate *** identified cyanotoxins in the reservoirs over the past three years,a phenomenon previously unreported in the *** that these reservoirs are drinking water sources for human populations,ongoing and systematic monitoring is needed to protect public *** the proliferation of algae and cyanobacteria in reservoirs requires resource management at the watershed level,and in the case of the Itiyuro and El Limon,requires binational management with Bolivia.

关键词： HABs Freshwater South America Toxins

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