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Native Americans domesticated maize (Zea mays ssp. mays) from lowland teosinte parviglumis (Zea mays ssp. parviglumis) in the warm Mexican southwest and brought it to the highlands of Mexico and South America where it was exposed to lower temperatures that imposed strong selection on flowering time. Phospholipids are important metabolites in plant responses to low-temperature and phosphorus availability and have been suggested to influence flowering time. Here, we combined linkage mapping with genome scans to identify High PhosphatidylCholine 1 (HPC1), a gene that encodes a phospholipase A1 enzyme, as a major driver of phospholipid variation in highland maize. Common garden experiments demonstrated strong genotype-by-environment interactions associated with variation at HPC1, with the highland HPC1 allele leading to higher fitness in highlands, possibly by hastening flowering. The highland maize HPC1 variant resulted in impaired function of the encoded protein due to a polymorphism in a highly conserved sequence. A meta-analysis across HPC1 orthologs indicated a strong association between the identity of the amino acid at this position and optimal growth in prokaryotes. Mutagenesis of HPC1 via genome editing validated its role in regulating phospholipid metabolism. Finally, we showed that the highland HPC1 allele entered cultivated maize by introgression from the wild highland teosinte Zea mays ssp. mexicana and has been maintained in maize breeding lines from the Northern United States, Canada, and Europe. Thus, HPC1 introgressed from teosinte mexicana underlies a large metabolic QTL that modulates phosphatidylcholine levels and has an adaptive effect at least in part via induction of early flowering time.
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Adaptación Fisiológica , Flores , Interacción Gen-Ambiente , Fosfatidilcolinas , Fosfolipasas A1 , Proteínas de Plantas , Zea mays , Alelos , Mapeo Cromosómico , Flores/genética , Flores/metabolismo , Genes de Plantas , Ligamiento Genético , Fosfatidilcolinas/metabolismo , Fosfolipasas A1/clasificación , Fosfolipasas A1/genética , Fosfolipasas A1/metabolismo , Proteínas de Plantas/clasificación , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Zea mays/genética , Zea mays/crecimiento & desarrolloRESUMEN
Iodine is an essential micronutrient for humans due to its fundamental role in the biosynthesis of thyroid hormones. As a key parameter to assess health conditions, iodine intake needs to be monitored to ascertain and prevent iodine deficiency. Iodine is available from various food sources (such as seaweed, fish, and seafood, among others) and dietary supplements (multivitamins or mineral supplements). In this work, a microfluidic paper-based analytical device (µPAD) to quantify iodide in seaweed and dietary supplements is described. The developed µPAD is a small microfluidic device that emerges as quite relevant in terms of its analytical capacity. The quantification of iodide is based on the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by hydrogen peroxide in the presence of iodine, which acts as the catalyst to produce the blue form of TMB. Additionally, powder silica was used to intensify and uniformize the colour of the obtained product. Following optimization, the developed µPAD enabled iodide quantification within the range of 10-100 µM, with a detection limit of 3 µM, and was successfully applied to seaweeds and dietary supplements. The device represents a valuable tool for point-of-care analysis, can be used by untrained personnel at home, and is easily disposable, low-cost, and user-friendly.
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Yodo , Técnicas Analíticas Microfluídicas , Humanos , Microfluídica , Yoduros , Suplementos Dietéticos/análisis , Yodo/análisis , Dispositivos Laboratorio en un Chip , PapelRESUMEN
Plant glucanases and chitinases are defense proteins that participate in pathogenesis; however, very little is known about the glucanase (GLUC) and chitinase (CHIT) gene families in mango. Some mango cultivars are of great economic importance and can be affected by anthracnose, a postharvest disease caused by fungi of the genus Colletotrichum spp. This study identified and characterized 23 putative glucanases and 16 chitinases in the mango genome cv. Tommy Atkins. We used phylogenetic analyses to classify the glucanases into three subclasses (A, B, and C) and the chitinases into four classes (I, II, IV, and V). Information on the salicylic, jasmonic acid, and ethylene pathways was obtained by analyzing the cis-elements of the GLUC and CHIT class I and IV gene promoters. The expression profile of GLUC, CHIT class I, and CHIT class IV genes in mango cv. Ataulfo inoculated with two Colletotrichum spp. revealed different profile expression related to these fungi's level of virulence. In general, this study provides the basis for the functional validation of these target genes with which the regulatory mechanisms used by glucanases and chitinases as defense proteins in mango can be elucidated.
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Quitinasas , Colletotrichum , Regulación de la Expresión Génica de las Plantas , Mangifera , Filogenia , Enfermedades de las Plantas , Colletotrichum/patogenicidad , Colletotrichum/genética , Mangifera/microbiología , Mangifera/genética , Quitinasas/genética , Quitinasas/metabolismo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Glicósido Hidrolasas/genética , Glicósido Hidrolasas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Perfilación de la Expresión GénicaRESUMEN
OBJECTIVE: Oncology guidelines for distress management recommend use of the single-item distress thermometer (DT) and accompanying Problem List (PL) to identify patients with high distress levels and their potential sources of distress. However, oncology practices have yet to establish standardized protocols to screen and triage caregivers with high distress levels. With an eye toward integrating caregiver-centered support services into cancer care, this mixed-methods study sought to assess caregiver distress and challenges that may contribute to their distress. METHODS: Nineteen caregivers of metastatic breast cancer patients (60% female, 47% ethnic/racial minority) completed an interview and a survey comprised of the DT, the original 39-item PL, and five additional caregiver-specific PL items. RESULTS: Caregivers reported moderate distress levels and more than half exceeded the National Comprehensive Cancer Network (NCCN) cut-off, denoting significant distress. There was no association between caregiver distress and the number of items endorsed on the original PL. Qualitative analysis identified nine problem domains as areas of caregiver unmet need needs (i.e., practical challenges, caregiving responsibilities, social/relationship issues, caregiver and patient emotional well-being, caregiver and patient physical well-being, spiritual well-being, and communication). Two of the problem domains (caregiving responsibilities and communication) were not captured in any way by the original PL. CONCLUSION: With further research and development, the identified domains could serve as the basis for a caregiver-specific PL to facilitate triage and referral when incorporated as part of routine distress screening.
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BACKGROUND: The COVID-19 pandemic has created unprecedented stressors for caregivers due to social distancing requirements that simultaneously increased their responsibilities and reduced opportunities for social connection and support. This concurrent embedded mixed-methods study examined differences between caregivers and non-caregivers regarding the effects of social connectedness on perceived stress and explored challenges caregivers experienced related to social connectedness and perceived stress. METHOD: A national online survey containing forced-choice and free-response questions was administered between April and June 2020. The survey was distributed via social media advertisements and a crowdsourcing platform to eligible adult residents in the United States (US) fluent in either English or Spanish. Multivariable regression and thematic analysis were used to analyze the quantitative and qualitative data. Mixed-methods integration occurred during the data analysis, interpretation, and reporting phases. RESULTS: The study sample comprised 1540 US adults (1275 non-caregivers, 265 caregivers; 65% women; 36% racial/ethnic minorities). Relative to non-caregivers, caregivers had lower levels of social connectedness and higher levels of perceived stress. Social connectedness was also inversely related to perceived stress for non-caregivers (p < 0.001) and slightly but not significantly positively related to perceived stress for caregivers. Qualitative findings showed caregivers experienced a variety of stressors including fear of COVID-19 exposure to their care recipients, disruption to usual care routines, and difficulty accessing healthcare services that may have contributed to decrements in social connectedness and higher levels of perceived stress. CONCLUSION: Findings suggest social connectedness may be beneficial for reducing perceived stress, but its impact can vary depending on individual circumstances. Overall, findings support the idea that caregivers are a particularly vulnerable sub-group of the population and may benefit from more targeted support and interventions.
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The unbalanced coagulation of blood is a life-threatening event that requires accurate and timely treatment. We introduce a user-friendly biomolecular platform based on modular RNA-DNA anticoagulant fibers programmed for reversible extracellular communication with thrombin and subsequent control of anticoagulation via a "kill-switch" mechanism that restores hemostasis. To demonstrate the potential of this reconfigurable technology, we designed and tested a set of anticoagulant fibers that carry different thrombin-binding aptamers. All fibers are immunoquiescent, as confirmed in freshly collected human peripheral blood mononuclear cells. To assess interindividual variability, the anticoagulation is confirmed in the blood of human donors from the U.S. and Brazil. The anticoagulant fibers reveal superior anticoagulant activity and prolonged renal clearance in vivo in comparison to free aptamers. Finally, we confirm the efficacy of the "kill-switch" mechanism in vivo in murine and porcine models.
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Aptámeros de Nucleótidos , Nanopartículas , Ácidos Nucleicos , Animales , Anticoagulantes , Aptámeros de Nucleótidos/química , Humanos , Leucocitos Mononucleares , Ratones , Porcinos , Trombina/químicaRESUMEN
Over the last four decades, vanadium compounds have been extensively studied as potential antidiabetic drugs. With the present review, we aim at presenting a general overview of the most promising compounds and the main results obtained with in vivo studies, reported from 1899-2023. The chemistry of vanadium is explored, discussing the importance of the structure and biochemistry of vanadate and the impact of its similarity with phosphate on the antidiabetic effect. The spectroscopic characterization of vanadium compounds is discussed, particularly magnetic resonance methodologies, emphasizing its relevance for understanding species activity, speciation, and interaction with biological membranes. Finally, the most relevant studies regarding the use of vanadium compounds to treat diabetes are summarized, considering both animal models and human clinical trials. An overview of the main hypotheses explaining the biological activity of these compounds is presented, particularly the most accepted pathway involving vanadium interaction with phosphatase and kinase enzymes involved in the insulin signaling cascade. From our point of view, the major discoveries regarding the pharmacological action of this family of compounds are not yet fully understood. Thus, we still believe that vanadium presents the potential to help in metabolic control and the clinical management of diabetes, either as an insulin-like drug or as an insulin adjuvant. We look forward to the next forty years of research in this field, aiming to discover a vanadium compound with the desired therapeutic properties.
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Diabetes Mellitus , Compuestos de Vanadio , Animales , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/química , Compuestos de Vanadio/farmacología , Compuestos de Vanadio/uso terapéutico , Compuestos de Vanadio/química , Vanadio/química , Diabetes Mellitus/tratamiento farmacológico , Insulina/uso terapéutico , Insulina Regular Humana/uso terapéuticoRESUMEN
In this work we pursued research involving the microwave-assisted N-alkylation of a NH pyrrolidine-fused chlorin with methyl 4-(bromomethyl) benzoate and subsequent ester hydrolysis as a straightforward strategy to obtain carboxylic acid functionality in the pyrrolidine-fused chlorin, as a single reaction product. We studied the reaction's scope by extending the N-alkylation of the free-base chlorin and its corresponding Zn(II) complex to other alkyl halides, including 1,4-diiodobutane, N-(2-bromoethyl)phthalimide, and 2-bromoethanaminium bromide. In addition, two new chlorin-dansyl dyads were synthesized by reacting dansyl chloride with the 2-aminoethyl pyrrolidine-fused chlorin (dyad 6) and NH pyrrolidine-fused chlorin (dyad 7). According to spectral studies, the linker length between the two fluorophores influences the response of the dyads to the solvent polarity. Because of the simplicity of these approaches, we believe it will enable access to a vast library of custom-tailored N-functionalized chlorins while preserving their important absorption and emission spectra as photosensitizers in photodynamic therapy (PDT) of cancer and photodynamic inactivation (PDI) of microorganisms.
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Latino day laborers (LDLs) are at a high risk for injury and accidents at work and have limited socioeconomic resources to deal with their consequences. While little is known about LDLs' perceptions of their own vulnerability at the workplace, less is known about the strategies they adopt to confront these risks. The purpose of this qualitative study was to assess LDLs' perceptions of their workplace dangers and to document the strategies they adopt and endorse to confront them. Guided by a participatory research approach, four focus groups stratified by age were conducted with 34 LDLs in Houston, Texas. Main focus group themes were identified using a combination of qualitative analysis methods involving a thematic analysis conducted by the interview team, LDL advisors, and bilingual Latino researchers. All participants were Latino males (mean age = 40), the majority reported having completed sixth grade or less (64.2%) and having lived in the United States for an average of 12.7 years. We described three categories of strategies to reduce risk for workplace injury generated by local LDLs (practical knowledge and job experience, interpersonal, and personal). These strategies should be explored and encouraged to assist in planning risk-reduction programs, presented in the voice and language of Latino "inside experts" with firsthand experience. The findings of the focus group suggest that LDLs already possess a broad repertoire of strategies to cope with risks at work that can be incorporated in safety programs for LDLs and other immigrant Latino workers.
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Emigrantes e Inmigrantes , Conductas Relacionadas con la Salud , Hispánicos o Latinos , Salud Laboral , Adulto , Humanos , Grupos Focales , Texas , Estados Unidos , Lugar de TrabajoRESUMEN
BACKGROUND: An expanding body of research documents the benefits of physical activity for cancer survivors' physical functioning and quality of life, but few successful models provide community-based physical activity programs to cancer survivors. This report presents an evaluation of Active Living After Cancer, an evidence-based physical activity program for breast cancer survivors, adapted for community delivery to minority and medically underserved survivors. METHODS: Survivors were recruited from health care and community settings. The program consisted of 12 weekly group sessions providing training in cognitive and behavioral skills for behavior change, brief physical activity, and cancer survivorship-related content. At the baseline and follow-up, participants completed assessments of their physical activity, quality of life, and physical functioning (6-minute walk and 30-second sit-to-stand test). At follow-up, they also completed questionnaires to measure program content mastery and satisfaction. RESULTS: The outcome analysis included 127 participants. Physical activity and quality of life (mental and physical) improved from the baseline to follow-up (all P < .01). Physical functioning improved, with increases in sit-to-stand repetitions (mean, 12.5 at the baseline vs 14.9 at the follow-up; P < .01) and 6-minute walk distances (mean, 428 m at the baseline vs 470 m at the follow-up; P < .01). CONCLUSIONS: The results highlight the effectiveness of an evidence-based program adapted for community-based delivery to minority and medically underserved breast cancer survivors. The program could be delivered to improve outcomes in diverse survivor populations. LAY SUMMARY: Physical activity in breast cancer survivors is related to better quality of life and longer cancer-free survival. However, there are few community-based programs to help breast cancer survivors to become more physically active. The Active Living After Cancer program was adapted from an evidence-based program and delivered in community-based settings to minority and medically underserved breast cancer survivors. It consisted of 12 weekly group sessions in which participants learned skills to increase their physical activity. The program participants increased their physical activity and improved their mental and physical well-being and physical functioning.
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Neoplasias de la Mama , Supervivientes de Cáncer , Neoplasias de la Mama/psicología , Neoplasias de la Mama/terapia , Supervivientes de Cáncer/psicología , Ejercicio Físico , Femenino , Humanos , Área sin Atención Médica , Calidad de Vida , Sobrevivientes/psicologíaRESUMEN
INTRODUCTION: The SARS-CoV-2 pandemic with psychiatric comorbidities leads to a scenario in which the use of psychotropic drugs may be required. This requires the support of evidence-based medicine to take into account possible interactions between antidepressants, mood stabilizers, benzodiazepines, and coronavirus infection treatments. METHODS: Three databases were consulted: (a) Lexicomp Drug Interactions, (b) Micromedex Solutions Drugs Interactions, (c)Liverpool Drug Interaction Group for COVID-19 therapies. The CredibleMeds QTDrugs List was also queried. Hydroxychloroquine, chloroquine, azithromycin, lopinavir-ritonavir, remdesivir, favipiravir, tocilizumab, baricitinib, anakinra, and dexamethasone - drugs used for SARS-CoV-2 - were analyzed, and consensus recommendations are made. RESULTS: The potential interactions of agomelatine, desvenlafaxine, duloxetine, milnacipran, and vortioxetine with COVID-19 treatments shall be considered less risky. Antidepressant interactions with hydroxychloroquine, chloroquine, and azithromycin enhance the risk of QT prolongation, and ECG monitoring is advised for most antidepressants. Antidepressants with lopinavir/ritonavir involve multiple CYP enzyme interactions (except with milnacipran). Gabapentin, oxcarbazepine, pregabalin, topiramate, and zonisamide are safe treatment options that have no significant interactions with COVID-19 treatments. Lithium is contraindicated with hydroxychloroquine, chloroquine, and azithromycin. Precaution should be taken in using valproic acid with lopinavir-ritonavir. The use of benzodiazepines does not present a risk of drug interaction with COVID-19 treatments, except lopinavir/ritonavir. CONCLUSIONS: Clinicians prescribing antidepressants, mood stabilizers/anticonvulsants, and benzodiazepines, should be aware of the probable risk of drug-drug interaction with COVID-19 medications and may benefit from heeding these recommendations for use to ensure patient safety.
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Tratamiento Farmacológico de COVID-19 , Anticonvulsivantes , Antidepresivos , Antivirales/uso terapéutico , Benzodiazepinas , Interacciones Farmacológicas , Humanos , SARS-CoV-2RESUMEN
In healthy individuals, virtually all blood plasma iron is bound by transferrin. However, in several diseases and clinical conditions, hazardous non-transferrin-bound iron (NTBI) species occur. NTBI represents a potentially toxic iron form, being a direct cause of oxidative stress in the circulating compartment and tissue iron loading. The accumulation of these species can cause cellular damage in several organs, namely, the liver, spleen, and heart. Despite its pathophysiological relevance, the chemical nature of NTBI remains elusive. This has precluded its use as a clinical biochemical marker and the development of targeted therapies. Herein, we make a critical assessment of the current knowledge of NTBI speciation. The currently accepted hypotheses suggest that NTBI is mostly iron bound to citric acid and iron bound to serum albumin, but the chemistry of this system remains fuzzy. We explore the complex chemistry of iron complexation by citric acid and its implications towards NTBI reactivity. Further, the ability of albumin to bind iron is revised and the role of protein post-translational modifications on iron binding is discussed. The characterization of the NTBI species structure may be the starting point for the development of a standardized analytical assay, the better understanding of these species' reactivity or the identification of NTBI uptake mechanisms by different cell types, and finally, to the development of new therapies.
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Sobrecarga de Hierro , Transferrina , Transporte Biológico , Humanos , Hierro/química , Sobrecarga de Hierro/metabolismo , Hígado/metabolismo , Transferrina/metabolismoRESUMEN
Functionalization of xanthene fluorophores with specific receptor units is an important topic of research aiming for the development of new analytical tools for biological sciences, clinical diagnosis, food and environmental monitoring. Herein, we report a new dihydrorosamine containing two active amino groups, which was functionalized with 3-benzyloxy-1-(3'-carboxypropyl)-2-methyl-4-pyridinone through an amide coupling strategy. Benzylated mono- and di-functionalized dihydrorosamine derivatives (H in position 9 of the xanthene) were obtained, but with modest reaction yields, requiring long and laborious purification procedures. Looking for a more efficient approach, rhodamine 110 was selected to react with the carboxypropyl pyridinone, enabling the isolation of the corresponding mono- and di-functionalized derivatives in amounts that depend on the excess of pyridinone added to the reaction. The structure of all compounds was established by 1H and 13C NMR, MS (ESI) and their absorption and emission properties were evaluated in dichloromethane. The fluorescence behavior of the debenzylated mono-rhodamine 110 derivative in the presence of Fe(III) was studied, making it an interesting fluorogenic dye for future optical sensing applications.
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The effects of hydrostatic (HHP) and dynamic (HPH) high-pressure treatments on the activity of pectin methylesterase (PME) and polyphenol oxidase (PPO) as well as the physicochemical quality attributes of 'Ataulfo' mango nectar were assessed. HHP reduced PME relative activity by 28% at 100 MPa for 5 min but increased PPO activity almost five-fold. Contrarily, HPH did not affect PME activity, but PPO was effectively reduced to 10% of residual activity at 300 MPa and at three passes. Color parameters (CIEL*a*b*), °hue, and chroma were differently affected by each type of high-pressure processing technology. The viscosity and fluid behavior were not affected by HHP, however, HPH changed the apparent viscosity at low dynamic pressure levels (100 MPa with one and three passes). The viscosity decreased at high shear rates in nectar samples, showing a shear-thinning effect. The results highlight how different effects can be achieved with each high-pressure technology; thus, selecting the most appropriate system for processing and preserving liquid foods like fruit beverages is recommended.
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Bebidas , Hidrolasas de Éster Carboxílico/química , Frutas/enzimología , Mangifera/enzimología , Proteínas de Plantas/química , Presión HidrostáticaRESUMEN
Iron (Fe) deficiency chlorosis (IDC) affects the growth of several crops, especially when growing in alkaline soils. The application of synthetic Fe-chelates is one of the most commonly used strategies in IDC amendment, despite their associated negative environmental impacts. In a previous work, the Fe-chelate tris(3-hydroxy-1-(H)-2-methyl-4-pyridinonate) iron(III) [Fe(mpp)3 ] has shown great potential for alleviating IDC in soybean (Glycine max) in the early stages of plant development under hydroponic conditions. Herein, its efficacy was verified under soil conditions in soybean grown from seed to full maturity. Chlorophyll levels, plant growth, root and shoot mineral accumulation (K, Mg, Ca, Na, P, Mn, Zn, Ni, and Co) and FERRITIN expression were accessed at V5 phenological stage. Compared to a commonly used Fe chelate, FeEDDHA, supplementation with [Fe(mpp)3 ] led to a 29% higher relative chlorophyll content, 32% higher root biomass, 36% higher trifoliate Fe concentration, and a twofold increase in leaf FERRITIN gene expression. [Fe(mpp)3 ] supplementation also resulted in increased accumulation of P, K, Zn, and Co. At full maturity, the remaining plants were harvested and [Fe(mpp)3 ] application led to a 32% seed yield increase when compared to FeEDDHA. This is the first report on the use of [Fe(mpp)3 ] under alkaline soil conditions for IDC correction, and we show that its foliar application has a longer-lasting effect than FeEDDHA, induces efficient root responses, and promotes the uptake of other nutrients.
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Anemia Hipocrómica , Glycine max , Hierro , Raíces de Plantas , PiridonasRESUMEN
Indomethacin is a potent non-steroidal anti-inflammatory drug (NSAID) with a strong selective inhibitor activity towards cyclooxygenase-2 (COX-2), an enzyme that is highly overexpressed in various tumour cells, being involved in tumourigenesis. Concomitantly, porphyrins have gained much attention as promising photosensitizers (PSs) for the non-invasive photodynamic therapy (PDT) of cancer. Herein, we report the design, and determine the singlet oxygen generation capacity and in vitro cellular toxicity of porphyrin- and chlorin-indomethacin conjugates (P2-Ind and C2-Ind). Both the conjugates were obtained in high yields and were characterized by 1H, 19F and 13C NMR as well as by high resolution mass spectrometry. The singlet oxygen generation properties were assessed by the 1,3-diphenylisobenzofuran singlet oxygen trap method, which showed that C2 and C2-Ind are the best singlet oxygen photosensitizers. In addition, it was found that the presence of indomethacin did not influence the singlet oxygen generation of porphyrin or chlorin. Cytotoxicity studies of the conjugate in human HEp2 cells revealed that the porphyrin- and chlorin-indomethacin conjugates have similar dark cytotoxicities, while chlorin C2 was shown to be the most phototoxic. Despite having lower cellular uptake than C2-Ind after 24 hours, chlorin C2 had a broad localization in HEp2 cells while the chlorin-indomethacin conjugate C2-Ind could be detected in the form of small aggregates. DFT calculations were performed to shed light on the reaction energy involved in the formation of the indomethacin conjugates and to compare the relative stability of selected isomers in solution. Moreover, the calculated energy of their first excited triplet state structures confirmed their use as suitable photosensitizers to generate singlet oxygen for PDT.
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FotoquimioterapiaRESUMEN
Nucleic acid-based assemblies that interact with each other and further communicate with the cellular machinery in a controlled manner represent a new class of reconfigurable materials that can overcome limitations of traditional biochemical approaches and improve the potential therapeutic utility of nucleic acids. This notion enables the development of novel biocompatible 'smart' devices and biosensors with precisely controlled physicochemical and biological properties. We extend this novel concept by designing RNA-DNA fibers and polygons that are able to cooperate in different human cell lines and that have defined immunostimulatory properties confirmed by ex vivo experiments. The mutual intracellular interaction of constructs results in the release of a large number of different siRNAs while giving a fluorescent response and activating NF-κB decoy DNA oligonucleotides. This work expands the possibilities of nucleic acid technologies by (i) introducing very simple design principles and assembly protocols; (ii) potentially allowing for a simultaneous release of various siRNAs together with functional DNA sequences and (iii) providing controlled rates of reassociation, stabilities in human blood serum, and immunorecognition.
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ADN/genética , FN-kappa B/genética , ARN/genética , Transcripción Genética , ADN/química , Transferencia Resonante de Energía de Fluorescencia , Regulación de la Expresión Génica/genética , Humanos , Oligodesoxirribonucleótidos/genética , Oligonucleótidos/química , Oligonucleótidos/genética , ARN/química , ARN Interferente Pequeño/genéticaRESUMEN
Radiation induces the generation of platelet-activating factor receptor (PAF-R) ligands, including PAF and oxidized phospholipids. Alternatively, PAF is also synthesized by the biosynthetic enzymes lysophosphatidylcholine acyltransferases (LPCATs) which are expressed by tumor cells including melanoma. The activation of PAF-R by PAF and oxidized lipids triggers a survival response protecting tumor cells from radiation-induced cell death, suggesting the involvement of the PAF/PAF-R axis in radioresistance. Here, we investigated the role of LPCATs in the melanoma cell radiotherapy response. LPCAT is a family of four enzymes, LPCAT1-4, and modular nucleic acid nanoparticles (NANPs) allowed for the simultaneous silencing of all four LPCATs. We found that the in vitro simultaneous silencing of all four LPCAT transcripts by NANPs enhanced the therapeutic effects of radiation in melanoma cells by increasing cell death, reducing long-term cell survival, and activating apoptosis. Thus, we propose that NANPs are an effective strategy for improving radiotherapy efficacy in melanomas.
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1-Acilglicerofosfocolina O-Aciltransferasa , Silenciador del Gen , Melanoma , Nanopartículas , Proteínas de Neoplasias , Ácidos Nucleicos , 1-Acilglicerofosfocolina O-Aciltransferasa/antagonistas & inhibidores , 1-Acilglicerofosfocolina O-Aciltransferasa/biosíntesis , Línea Celular Tumoral , Humanos , Melanoma/tratamiento farmacológico , Melanoma/enzimología , Nanopartículas/química , Nanopartículas/uso terapéutico , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/biosíntesis , Ácidos Nucleicos/química , Ácidos Nucleicos/farmacologíaRESUMEN
Predicting upcoming sensorimotor events means creating forward estimates of the body and the surrounding world. This ability is a fundamental aspect of skilled motor behavior and requires an accurate and constantly updated representation of the body and the environment. To test whether these prediction mechanisms could be affected by a peripheral injury, we employed an action observation and electroencephalogram (EEG) paradigm to assess the occurrence of prediction markers in anticipation of observed sensorimotor events in healthy and brachial plexus injury (BPI) participants. Nine healthy subjects and six BPI patients watched a series of video clips showing an actor's hand and a colored ball in an egocentric perspective. The color of the ball indicated whether the hand would grasp it (hand movement), or the ball would roll toward the hand and touch it (ball movement), or no event would occur (no movement). In healthy participants, we expected to find distinct electroencephalographic activation patterns (EEG signatures) specific to the prediction of the occurrence of each of these situations. Cluster analysis from EEG signals recorded from electrodes placed over the sensorimotor cortex of control participants showed that predicting either an upcoming hand movement or the occurrence of a tactile event yielded specific neural signatures. In BPI participants, the EEG signals from the sensorimotor cortex contralateral to the dominant hand in the hand movement condition were different compared to the other conditions. Furthermore, there were no differences between ball movement and no movement conditions in the sensorimotor cortex contralateral to the dominant hand, suggesting that BPI blurred specifically the ability to predict upcoming tactile events for the dominant hand. These results highlight the role of the sensorimotor cortex in creating estimates of both actions and tactile interactions in the space around the body and suggest plastic effects on prediction coding following peripheral sensorimotor loss.
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Mano/fisiología , Movimiento/fisiología , Corteza Sensoriomotora/fisiología , Percepción Espacial/fisiología , Tacto/fisiología , Adulto , Mapeo Encefálico/métodos , Electroencefalografía/métodos , Femenino , Fuerza de la Mano/fisiología , Humanos , Masculino , Percepción del Tacto/fisiología , Adulto JovenRESUMEN
Functional organic dyes play a key role in many fields, namely in biotechnology and medical diagnosis. Herein, we report two novel 2,3- and 3,4-dihydroxyphenyl substituted rosamines (3 and 4, respectively) that were successfully synthesized through a microwave-assisted protocol. The best reaction yields were obtained for rosamine 4, which also showed the most interesting photophysical properties, specially toward biogenic amines (BAs). Several amines including n- and t-butylamine, cadaverine, and putrescine cause spectral changes of 4, in UV-Vis and fluorescence spectra, which are indicative of their potential application as an effective tool to detect amines in acetonitrile solutions. In the gas phase, the probe response is more expressive for spermine and putrescine. Additionally, we found that methanolic solutions of rosamine 4 and n-butylamine undergo a pink to yellow color change over time, which has been attributed to the formation of a new compound. The latter was isolated and identified as 5 (9-aminopyronin), whose solutions exhibit a remarkable increase in fluorescence intensity together with a shift toward more energetic wavelengths. Other 9-aminopyronins 6a, 6b, 7a, and 7b were obtained from methanolic solutions of 4 with putrescine and cadaverine, demonstrating the potential of this new xanthene entity to react with primary amines.