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In the era dominated by plastic, the widespread use of plastic in our daily lives has led to a growing accumulation of its degraded byproducts, such as microplastics and plastic additives like Bisphenol A (BPA). BPA is recognized as one of the earliest man-made substances that exhibit endocrine-disrupting properties. It is frequently employed in the manufacturing of epoxy resins, polycarbonates, dental fillings, food storage containers, infant bottles, and water containers. BPA is linked to a range of health issues including obesity, diabetes, chronic respiratory illnesses, cardiovascular diseases, and reproductive abnormalities. This study examines the bacterial bioremediation of the BPA, which is found in many sources and is known for its hazardous effects on the environment. The metabolic pathways for the breakdown of BPA in important bacterial strains were hypothesized based on the observed altered intermediate metabolites during the degradation of BPA. This review discusses the enzymes and genes involved in the bacterial degradation of BPA. The utilization of naturally occurring microorganisms is the most efficient and cost-effective method due to their selectivity of strains, ensuring sustainability.
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Bacterias , Compuestos de Bencidrilo , Biodegradación Ambiental , Fenoles , Compuestos de Bencidrilo/metabolismo , Fenoles/metabolismo , Bacterias/metabolismo , Disruptores Endocrinos/metabolismo , Contaminantes Ambientales/metabolismoRESUMEN
The estrogen receptor (ER) is a well-established target for the treatment of breast cancer, with the majority of patients presenting as ER-positive (ER+). Endocrine therapy is a mainstay of breast cancer treatment but the development of resistance mutations in response to aromatase inhibitors, poor pharmacokinetic properties of fulvestrant, agonist activity of tamoxifen, and limited benefit for elacestrant leave unmet needs for patients with or without resistance mutations in ESR1, the gene that encodes the ER protein. Here we describe palazestrant (OP-1250), a novel, orally bioavailable complete ER antagonist and selective ER degrader. OP-1250, like fulvestrant, has no agonist activity on the ER and completely blocks estrogen-induced transcriptional activity. In addition, OP-1250 demonstrates favorable biochemical binding affinity, ER degradation, and antiproliferative activity in ER+ breast cancer models that is comparable or superior to other agents of interest. OP-1250 has superior pharmacokinetic properties relative to fulvestrant, including oral bioavailability and brain penetrance, as well as superior performance in wild-type and ESR1-mutant breast cancer xenograft studies. OP-1250 combines well with cyclin-dependent kinase 4 and 6 inhibitors in xenograft studies of ER+ breast cancer models and effectively shrinks intracranially implanted tumors, resulting in prolonged animal survival. With demonstrated preclinical efficacy exceeding fulvestrant in wild-type models, elacestrant in ESR1-mutant models, and tamoxifen in intracranial xenografts, OP-1250 has the potential to benefit patients with ER+ breast cancer.
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Neoplasias de la Mama , Tetrahidronaftalenos , Animales , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Fulvestrant/farmacología , Fulvestrant/uso terapéutico , Antagonistas del Receptor de Estrógeno/uso terapéutico , Ensayos Antitumor por Modelo de Xenoinjerto , Tamoxifeno , Estrógenos , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismoRESUMEN
In the innovative concept of the "Social Internet of Things" (IoT), the IoT is combined with social platforms so that inanimate devices can form their interactions with one another. Still, customers have a wary attitude toward this new standard. They worry that their privacy will be invaded and their information will be made public. IoT won't become a frontrunner technology until we have tried true techniques to improve trustworthy connections between nodes. As a result, data privacy becomes extremely difficult, further increasing the difficulty of providing high-quality services and absolute safety. Several articles have attempted to analyze this issue. To categorize safe nodes in the IoT network, they suggested many models based on various attributes and aggregation techniques. In contrast, prior works failed to provide a means of identifying fraudulent nodes or distinguishing between different forms of assaults. To identify attacks carried out by hostile nodes and separate them from the network, we propose a novel Multi-hop Convolutional Neural Network with an attention mechanism (MH-CNN-AM). To achieve the best performance in the suggested research, performance measures including accuracy, precision, recall, F1-score, and MAE are studied and compared with the of existing methodologies.
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Introduction: Bacterial spot disease of tomato was identified a few decades ago. The varying point of entry for the pathogen has enhanced the complexities for designing an effective disease management method. Recent advances in the use of inducers to elicit immune response in order to prepare the plant for a future attack by the pathogen are similar to the vaccination that is undertaken in humans and is a trending technology. Objectives: The present study aims at understanding the effect of salicylic acid (SA) for management of bacterial spot disease caused by Xanthomonas perforans. Methods: The study evaluated the effects of SA on the disease incidence along with seed germination and seedling vigor in two cultivars of tomato namely, Sun hybrid- resistant variety (R) and Quality- highly susceptible variety(HS). Results: The germination and seedling vigor, which was reduced in case of HS variety in comparison with that of the R variety, was notably improved after seed priming in both the cultivars. The antioxidant enzyme activities of ascorbate peroxidise (APx), catalase (CAT) and glutathione reductase (GR) were assessed which showed that the R variety reached maximum activity at 18 h post inoculation (hpi), 24 hpi and 21 hpi, respectively, whereas the HS variety reached maximum at 30 hpi for APx and 36 hpi for CAT and GR activities. The transcript accumulation using qRT-PCR was also evaluated showing mRNA accumulation was maximum in the R cultivar after SA priming at 1.5 mM concentration. Conclusion: the present study demonstrates the potential benefits of seed priming with SA to effectively elicit defence response in tomato seedlings against the bacterial spot disease.
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Paracetamol (PAR) is an effective antipyretic and analgesic drug utilized worldwide, safer at therapeutic levels but over-dosing and the chronic usage of PAR results in accumulation of toxic metabolites, which leads to kidney and liver damages. Hence, a simple, rapid, cost-effective, and sensitive analytical technique is needed for the accurate determination of PAR in pharmaceutical and biological samples. Though numerous techniques have been reported for PAR detection, electrochemical methods are being receiving more interest due to their advantages. Moreover, in the past few decades, room temperature ionic liquids (RTILs) have been utilized in electrochemical sensors due to their attractive properties. In this present review, authors gathered research findings available for the determination of PAR using RTIL-based electrochemical sensors and discussed. The advantages and limitations in these systems as well as the future research directions are summarized.
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Líquidos Iónicos , Acetaminofén , Carbono/química , Técnicas Electroquímicas/métodos , Electrodos , Líquidos Iónicos/química , TemperaturaRESUMEN
Hydrogeochemical and Health Risk Assessments of trace elements are integral to groundwater resource assessment, utilization, and human health. Investigation of groundwater chemistry and trace elemental impact on local inhabitants were attempted in Shanmuganadhi basin, Tamilnadu, India. About 60 groundwater samples were collected during the pre-monsoon period and analyzed for hydrochemical composition, including major and trace elements (Fe, Cr, Ni, Cu Pb, Mn, and As) to isolate chemical characteristics and human health risk assessment. Groundwater geochemistry is prejudiced by geochemical reactions uniting cation exchange, dissolution and precipitation, adsorption, and anthropogenic contributions. About thirty-two percent of groundwater samples recorded higher F-(>1.5 mg/L) than the prescribed limit suggests sources from rock weathering and silicate dissolution. Nitrates (>45.0 mg/L) suggest sources from agricultural influences. Water types indicate alkalis (Na+ + K+) dominating alkali earth (Ca2+ - Mg2+) and strong acids (Cl- and SO42-) looming weak acid (CO32- and HCO3-) irrespective of water samples. The geochemical stability diagram suggests precipitation of silica, carbonate, and magnesium and dissolution of sulphate minerals along the groundwater flow path. Significant correlation between major ions and trace elements (Pb, Mn, Ni, and Cu) suggests origin from rock weathering, human impacts, and cultivation practices. Non-carcinogenic human risk for trace elements was higher in children compared with adults via ingestion and dermal exposure. The carcinogenic result suggests that Cr in CHK (7.1 × 10-2) and HBG (4.3 × 10-2) have the most excellent chance of cancer risk. The environmental risk category attempted using Comprehensive risk factor (CRI) suggests Pb (3.2-CHK, 2.6-HBG) with potential cancer risk. The comprehensive evaluation index recommends environmental damage between mild to moderate, indicating continuous exposure of traceable elements might result in cancer cause to the inhabitants. The study suggests water quality seems to be prejudiced by various geological and anthropogenic causes and endorses counteractive measures and proper execution of existing laws to protect groundwater resources in the study area.
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Agua Subterránea , Contaminantes Químicos del Agua , Adulto , Niño , Monitoreo del Ambiente , Agua Subterránea/química , Humanos , India , Nitratos/análisis , Contaminantes Químicos del Agua/análisis , Calidad del AguaRESUMEN
Chemical weathering in a groundwater basin is a key to understanding global climate change for a long-term scale due to its association with carbon sequestration. The present study aims to characterize and to quantify silicate weathering rate (SWR), carbon dioxide consumption rate and carbonate weathering rate (CWR) in hard rock terrain aided by major ion chemistry. The proposed study area Shanmuganadhi is marked with superior rainfall, oscillating temperature and runoff with litho-units encompassing charnockite and hornblende-biotite gneiss. Groundwater samples (n = 60) were collected from diverse locations and analysed for major chemical constituents. Groundwater geochemistry seems to be influenced by geochemical reactions combining dissolution and precipitation of solids, cation exchange and adsorption along with minor contribution from anthropogenic activities. The SWR calculated for charnockite and hornblende-biotite gneiss was 3.07 tons km-2 year-1 and 5.12 tons km-2 year-1, respectively. The calculated CWR of charnockite and hornblende-biotite gneiss was 0.079 tons km-2 year-1 and 0.74 tons km-2 year-1, respectively. The calculated CO2 consumption rates via silicate weathering were 1.4 × 103 mol km-2 year-1 for charnockite and 5.8 × 103 mol km-2 year-1 for hornblende-biotite gneiss. Lithology, climate and relief were the key factors isolated to control weathering and CO2 consumption rates.
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Dióxido de Carbono/química , Agua Subterránea/química , Secuestro de Carbono , Carbonatos/química , Clima , Monitoreo del Ambiente , Geología , India , Silicatos/análisis , Contaminantes Químicos del Agua/químicaRESUMEN
Submarine groundwater discharge and associated trace element fluxes from the Coleroon River estuary to south bay, India, has been attempted, because increasing trace elements could result in harmful algal blooms and eutrophication. Trace elements (Al, Cr, Mn, Fe, Ni, Cu, Zn, Sr, Mo, Ba, Pb, Th, and U) in surface water, pore, and groundwater samples were monitored for 10 days in three locations (A, B, and C) by considering tidal fluctuations. The trace elements Al, Cr, Fe, Ni, Zn, Sr, Mo, Pb, Th, and U were greater and found to be influenced by processes, such as fresh groundwater discharge and seawater intrusion. Lower Mn, Cu, and Ba signifies impact due to sediment adsorption, mixing, and elemental exchange during fresh groundwater and seawater mixing. Salinity versus trace element plot infers greater trace element mobility with cumulative salinity influenced by the conformist behavior of freshwater, seawater, and mixing. The calculated submarine groundwater discharge supported dissolved trace elements fluxes were 107,047.8 n mol d-1 m-1 for location A, 183,520.2 n mol d-1 m-1 for location B, and 181,474.4 n mol d-1 m-1 for location C, respectively. Variations in dissolved trace elements fluxes are attributed to variations in pH, free redox environment in the aquifer, adsorption or desorption by sediments, and the environmental cycle of marine organisms.
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Bahías/química , Monitoreo del Ambiente/métodos , Estuarios , Agua Subterránea/química , Oligoelementos/análisis , Contaminantes Químicos del Agua/análisis , Adsorción , Sedimentos Geológicos/química , India , Ríos/química , Agua de Mar/químicaRESUMEN
The increasing interest in developing potent non-toxic drugs in medicine is widening the opportunities for studying the usage of nanostructures in the treatment of various diseases. The present work reports a method for a facile and an eco-friendly synthesis of silver nanoparticles (AgNPs) using Terminalia chebula fruit extract (TCE). The obtained AgNPs was characterized by using different spectroscopic and microscopic techniques. The analysis of the results revealed that the as-obtained AgNPs have spherical morphology with an average diameter of 22 nm. Furthermore, the preliminary bioactivity evaluations revealed that the bio-conjugation of AgNPs, using TCE, significantly enhanced the antibacterial and anti-breast cancer potentials of the latter. The antibacterial activity of the as-prepared AgNPs showed that B. subtilis was more sensitive towards the AgNPs, followed by P. aeruginosa; while, E. coli and S. mutans showed comparatively minimal sensitivity toward the AgNPs. The IC50 values of TCE, AgNPs and TCE + AgNPs treatment of MCF-7 were found to be 17.53, 14.25 and 6.484 µg/mL, respectively. Therefore, it can be ascertained that the bio-conjugation may provide a headway with regard to the therapeutic employment of T. chebula, upon mechanistically understanding the basis of observed antibacterial and anticancer activities.
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Antiinfecciosos , Bacillus subtilis/crecimiento & desarrollo , Neoplasias de la Mama/tratamiento farmacológico , Citotoxinas , Frutas/química , Nanopartículas del Metal , Extractos Vegetales/química , Plata , Terminalia/química , Antiinfecciosos/síntesis química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Citotoxinas/síntesis química , Citotoxinas/química , Citotoxinas/farmacología , Femenino , Humanos , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Plata/química , Plata/farmacologíaRESUMEN
Groundwater contributed nutrients aided with increasing population threaten the global coastal ecosystems. In this study, attempt has been made using major ions and nutrients to evaluate the significance of submarine groundwater discharge (SGD) in a semi-arid estuary of south India. Surface, seepage and groundwater chemistry altered from fresh (NaK-CaMg-NO3Cl) to mixed (NaK-NO3Cl) to saline water (NaCl) type from upstream to outlet that connects Bay of Bengal. We predicted abundant nitrate (NO3-) along upstream and towards the bay due to application of fertilizers and aquaculture activities, respectively. Elevated ammonium (NH4+) observed in the recirculated groundwater/sea water suggests contribution from sea water intrusion and higher phosphate (PO43-) noted at the outer bay suggests sources from phosphatic nodules. Decreasing Redfield ratio towards the bay suggests anoxic aquifer condition due to salinization. The SGD driven nutrient fluxes were 40.0-47.0% for NO3-, 43.0-51.0% for NH4+ and 9.0-32.0% for PO43- from the total input fluxes. The estimated nutrient fluxes showed that NO3- and PO43- discharges to the sea due to SGD and NH4+ removed from the coast due to consumption by microorganisms that creates toxic algal blooms in the study area.
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Agua Subterránea , Ríos , Bahías , Ecosistema , Monitoreo del Ambiente , Estuarios , India , Nutrientes , Agua de MarRESUMEN
Transforming growth factor ß (TGFß) signaling has been recently shown to reduce antitumor response to PD-L1 blockade, leading to a renewed enthusiasm in developing anti-TGFß therapies for potential combination with cancer immunotherapy agents. Inhibition of TGFß signaling in nonclinical toxicology species is associated with serious adverse toxicities including cardiac valvulopathies and anemia. Previously, cardiovascular toxicities have been thought to be limited to small molecule inhibitors of TGFß receptor and not considered to be a liability associated with pan-TGFß neutralizing monoclonal antibodies (mAbs). Here, we report the toxicity findings associated with a potent pan-TGFß neutralizing mAb (pan-TGFß mAb; neutralizes TGFß1, 2, and 3) after 5 weekly intravenous doses of 10, 30, and 100 mg/kg, followed by a 4-week recovery period, in mice and cynomolgus monkeys. Mortality was observed due to acute bleeding and cardiovascular toxicity in mice at ≥ 30 mg/kg and prolonged menstruation in female monkeys at 100 mg/kg. Additional findings considered to be on-target exaggerated pharmacology included generalized bleeding and cardiovascular toxicity in mice and monkeys; histopathologic changes in the teeth, tongue, and skin in mice; and abnormal wound healing and microscopic pathology in the bone in monkeys. Importantly, our data indicate that the cardiovascular toxicities associated with the inhibition of TGFß signaling are not limited to small molecule inhibitors but are also observed following administration of a potent pan-TGFß inhibiting mAb.
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Anticuerpos Monoclonales Humanizados/toxicidad , Anticuerpos Neutralizantes/toxicidad , Enfermedades Cardiovasculares/inducido químicamente , Corazón/efectos de los fármacos , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Animales , Anticuerpos Monoclonales Humanizados/sangre , Anticuerpos Neutralizantes/sangre , Cardiotoxicidad , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , Línea Celular , Femenino , Hemorragia/inducido químicamente , Hemorragia/metabolismo , Humanos , Macaca fascicularis , Masculino , Ratones , Miocardio/metabolismo , Miocardio/patología , Medición de Riesgo , Factores de Tiempo , Pruebas de Toxicidad , Toxicocinética , Factor de Crecimiento Transformador beta/inmunología , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Attempt has been made to discriminate groundwater salinity causes along the east coast of India. A total of 122 groundwater samples (61/season) were collected for two diverse seasons (Pre Monsoon and Post Monsoon) and analyzed for physical and chemical components along with stable isotopes. The Piper diagram proposes samples along the coast predisposed by saltwater incursion. Ionic ratio plots recommend groundwater discriminatory by changing geochemical signatures. The statistical correlation suggests impact of saltwater incursion, anthropogenic and rock water interaction as sources for dissolved constituents in groundwater. The thermodynamic stability plot suggests higher silicate dissolution, weathering and ion exchange prompting water chemistry nevertheless of seasons. The δ18O and δ2H increases towards the sea suggesting enrichment attributed to the sea water influence and rainfall influences along the southwestern parts of the study area.
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Monitoreo del Ambiente/métodos , Agua Subterránea/química , Salinidad , Agua de Mar/química , Contaminantes Químicos del Agua/análisis , India , Isótopos/análisis , Estaciones del Año , TermodinámicaRESUMEN
Silver nanoparticle was synthesized using D-glucosamine chitosan base as green reducing agent at elevated temperature in alkaline pH ranges. The excess of D-glucosamine chitosan base was used as it is both stabilizing and reducing agent at different pHs, regulates the shape and size of the silver nanoparticles. The progressive growth of silver nanoparticles was monitored by UV-Visible spectral studies. A sharp peak at 420â¯nm indicates the formation of spherical silver nanoparticles. The size and shape of silver nanoparticles were observed from Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) methods. The anisotropically grown nanoparticles were used as probe for Surface Enhanced Raman Studies (SERS) using ATP (4-aminothiophenol) as a model system. The catalytic behavior of silver nanoparticles was exploited for 4-nitrophenol reduction and observed that the reduction reaction follows pseudo first order kinetics with a rate constant 0.65â¯min. The antibacterial activity of silver nanoparticles was also tested for both gram-positive and -negative microorganisms, in which higher zone of inhibition was observed for gram negative microorganism.
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Antibacterianos/síntesis química , Antibacterianos/farmacología , Quitosano/química , Glucosamina/química , Nanopartículas del Metal/química , Plata/química , Plata/farmacología , Antibacterianos/química , Catálisis , Escherichia coli/efectos de los fármacos , Tecnología Química Verde , Pruebas de Sensibilidad Microbiana , Nanotecnología , Nitrofenoles/química , Oxidación-Reducción , Tamaño de la PartículaRESUMEN
Magnetically recoverable Au nanoparticles immobilized/stabilized on core-shell nanocomposites are synthesized by the combination of suspension polymerization as well as surface initiator atom transfer radical polymerization (SI-ATRP) methods. The magnetic core-shell supported Au nanocatalysts are namely Fe3O4-PAC-AuNPs, Fe3O4-PVBC-g-PAC-AuNPs, Fe3O4-HEA-AuNPs, and Fe3O4-PVBC-g-HEA-AuNPs. Among all the catalysts, Fe3O4-PVBC-g-PAC-Au NPs exhibited an excellent activity in the reduction of Rhodamine B with an apparent rate constant of 10.77 × 10-3 s-1 and TOF value of 47.62 × 10-3 s-1 under pseudo-first order reaction condition. Further, Fe3O4-PVBC-g-PAC-Au NPs has an outstanding activity and recyclability without applying any external magnetic field. This new approach provides an exciting potential way in the preparation of recyclable metal nano-catalysts with high catalytic activity.
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Nucleophosmin (NPM1) is a nucleolar protein that is frequently overexpressed in various types of solid tumors. NPM1 is involved in several cellular processes that might contribute significantly to the increased proliferation potential of cancers. Previous reports suggest that NPM1 expression is highly increased in response to mitogenic and oncogenic signals, the mechanisms of which have not been elucidated extensively. Using constructs incorporating different fragments of the NPM1 promoter upstream to a Luciferase reporter gene, we have identified the minimal promoter of NPM1 and candidate transcription factors regulating NPM1 promoter activity by luciferase reporter assays. We have validated the roles of a few candidate factors at the transcriptional and protein level by quantitative reverse transcriptase PCR, immunoblotting and immunohistochemistry, and explored the mechanism of regulation of NPM1 expression using immunoprecipitation and chromatin immunoprecipitation assays. We show here that the expression of NPM1 is regulated by transcription factor c-fos, a protein that is strongly activated by growth factor signals. In addition, mutant p53 (R175H) overexpression also enhances NPM1 expression possibly through c-myc and c-fos. Moreover, both c-fos and mutant p53 are overexpressed in oral tumor tissues that showed NPM1 overexpression. Collectively, our results suggest that c-fos and mutant p53 R175H positively regulate NPM1 expression, possibly in synergism, that might lead to oncogenic manifestation.
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Carcinoma de Células Escamosas/patología , Regulación Neoplásica de la Expresión Génica , Genes fos , Neoplasias de la Boca/patología , Mutación , Proteínas Nucleares/genética , Proteína p53 Supresora de Tumor/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Proliferación Celular , Humanos , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Proteínas Nucleares/metabolismo , Nucleofosmina , Pronóstico , Regiones Promotoras Genéticas , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/genéticaRESUMEN
BACKGROUND: p300 (KAT3B) lysine acetyltransferase activity is modulated under different physiological and pathological contexts through the induction of trans-autoacetylation. This phenomenon is mediated by several factors, mechanisms of which are not fully understood. METHODS: Through acetyltransferase assays using full-length, baculovirus-expressed KATs, the specificity of NPM1-mediated enhancement of p300 autoacetylation was tested. Chaperone assays and tryptophan fluorescence studies were performed to evaluate the NPM1-induced protein folding. The NPM1 oligomer-defective mutant characterization was done by glutaraldehyde-crosslinking. The small-molecule inhibitor of NPM1 oligomerization was used to confirm the absolute requirement of multimeric NPM1 in vivo. Immunohistochemistry analysis of oral cancer patient samples was done to uncover the pathophysiological significance of NPM1-induced p300 autoacetylation. RESULTS: We find that the histone chaperone NPM1 is a specific inducer of p300 autoacetylation. Distinct from its histone chaperone activity, NPM1 is a molecular chaperone of p300. The biophysical experiments suggest that there is a reversible binding between NPM1 and p300 which can modulate p300 acetyltransferase activity. Disruption of NPM1 oligomerization suggests that oligomeric NPM1 is essential for the induction of p300 autoacetylation. Significantly, we observe a concomitant hyper-autoacetylation of p300 with overexpression of NPM1 in oral cancer samples. CONCLUSION: NPM1 can specifically modulate p300 acetyltransferase activity through the enhancement of autoacetylation. The molecular chaperone activity and oligomerization of NPM1 play a pivotal role in this phenomenon. GENERAL SIGNIFICANCE: NPM1 is overexpressed in several solid cancers, the significance of which is unknown. Induction of p300 autoacetylation could be the cause of NPM1-mediated tumorigenicity.
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Proteína p300 Asociada a E1A/química , Proteína p300 Asociada a E1A/metabolismo , Histonas/metabolismo , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Pliegue de Proteína , Multimerización de Proteína , Neoplasias de la Lengua/metabolismo , Acetilación , Humanos , Nucleofosmina , Unión Proteica , Conformación Proteica , Neoplasias de la Lengua/patología , Células Tumorales CultivadasRESUMEN
Ketamine has been used as a pharmacological model for schizophrenia as subanesthetic infusions have been shown to produce temporary schizophrenia-like symptoms in healthy humans. More recently, ketamine has emerged as a potential treatment for multiple psychiatric disorders, including treatment-resistant depression and suicidal ideation. However, the mechanisms underlying both the psychotomimetic and the therapeutic effects of ketamine remain poorly understood. This review provides an overview of what is known of the neural mechanisms underlying the effects of ketamine and details what functional MRI studies have yielded at a systems level focused on brain circuitry. Multiple analytic approaches show that ketamine exerts robust and consistent effects at the whole-brain level. These effects are highly conserved across human and nonhuman primates, validating the use of nonhuman primate models for further investigations with ketamine. Regional analysis of brain functional connectivity suggests that the therapeutic potential of ketamine may be derived from a strengthening of executive control circuitry, making it an intriguing candidate for the treatment of drug abuse. There are still important questions about the mechanism of action and the therapeutic potential of ketamine that can be addressed using appropriate functional neuroimaging techniques.
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Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Antagonistas de Aminoácidos Excitadores/farmacología , Ketamina/farmacología , Imagen por Resonancia Magnética , Psicotrópicos/farmacología , Animales , Encéfalo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiologíaRESUMEN
AIMS: The aim of this study is to compare the effects of yoga program with supportive therapy counseling on mood states, treatment-related symptoms, toxicity, and quality of life in Stage II and III breast cancer patients on conventional treatment. METHODS: Ninety-eight Stage II and III breast cancer patients underwent surgery followed by adjuvant radiotherapy (RT) or chemotherapy (CT) or both at a cancer center were randomly assigned to receive yoga (n = 45) and supportive therapy counseling (n = 53) over a 24-week period. Intervention consisted of 60-min yoga sessions, daily while the control group was imparted supportive therapy during their hospital visits. Assessments included state-trait anxiety inventory, Beck's depression inventory, symptom checklist, common toxicity criteria, and functional living index-cancer. Assessments were done at baseline, after surgery, before, during, and after RT and six cycles of CT. RESULTS: Both groups had similar baseline scores. There were 29 dropouts 12 (yoga) and 17 (controls) following surgery. Sixty-nine participants contributed data to the current analysis (33 in yoga, and 36 in controls). An ANCOVA, adjusting for baseline differences, showed a significant decrease for the yoga intervention as compared to the control group during RT (first result) and CT (second result), in (i) anxiety state by 4.72 and 7.7 points, (ii) depression by 5.74 and 7.25 points, (iii) treatment-related symptoms by 2.34 and 2.97 points, (iv) severity of symptoms by 6.43 and 8.83 points, (v) distress by 7.19 and 13.11 points, and (vi) and improved overall quality of life by 23.9 and 31.2 points as compared to controls. Toxicity was significantly less in the yoga group (P = 0.01) during CT. CONCLUSION: The results suggest a possible use for yoga as a psychotherapeutic intervention in breast cancer patients undergoing conventional treatment.
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In selected patients with drug-resistant focal epilepsies (DRFE), who otherwise are likely to be excluded from epilepsy surgery (ES) because of the absence of a magnetic resonance imaging (MRI)-demonstrable lesion or discordant anatomo-electro-clinical (AEC) data, magnetoencephalography (MEG) may help to generate an AEC hypothesis and stereo-electroencephalography (SEEG) may help to verify the hypothesis and proceed with ES. The sensitivity of MEG is much better in localizing the spiking zone in relation to lateral temporal and extratemporal cortical regions compared to the mesial temporal structures. MEG has a dominant role in the presurgical evaluation of patients with MRI-negative DRFEs, insular epilepsies, and recurrent seizures after failed epilepsy surgeries, and in guiding placement of invasive electrodes. Moreover, postoperative seizure freedom is better if MEG spike source localized cortical region is included in the resection. When compared to subdural grid electrode recording, SEEG is less invasive and safer. Those who are otherwise destined to suffer from uncontrolled seizures and their consequences, SEEG guided ES is a worthwhile and a cost-effective option. Depending on the substrate pathology, there is > 80-90% chance of undergoing ES and 60-80% chance of becoming seizure-free following SEEG. Recent noninvasive techniques aimed at better structural imaging, delineating brain connectivity and recording specific intracerebral EEG patterns such as high frequency oscillations might decrease the need for SEEG; but more importantly, make SEEG exploration more goal-directed and hypothesis-driven.
Asunto(s)
Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/fisiopatología , Electroencefalografía , Magnetoencefalografía , Encéfalo/fisiopatología , Mapeo Encefálico , Electroencefalografía/métodos , Humanos , Imagen por Resonancia Magnética/métodos , Magnetoencefalografía/métodosRESUMEN
In the title 1-oxo-1,2-di-hydro-naphthalene derivatives, C28H24O6, (I), C34H22O5S, (II), and C27H20O3S2, (III), the cyclo-hexa-1,3-diene rings of the 1,2-di-hydro-naphthalene ring systems adopt half-chair, boat and half-chair conformations, respectively. The carbonyl O atoms attached to the di-hydro-naphthalene ring systems are each significantly deviated from the mean plane of the 1,2-di-hydro-naphthalene ring system, by 0.6162â (12)â Å in (I), 0.6016â (16)â Å in (II) and 0.515â (3)â Å in (III). The mean planes of the 1,2-di-hydro-naphthalene ring systems make dihedral angles of 85.83â (3), 88.19â (3) and 81.67â (8)°, respectively, with the methyl-phenyl ring in (I), the pyrene ring in (II) and the phenyl ring in (III). In (I), the mol-ecular structure is stabilized by an intra-molecular C-Hâ¯O hydrogen bond, generating an S(6) ring motif. In the crystal of (I), mol-ecules are linked by an inter-molecular C-Hâ¯O hydrogen bond, which generates a C(8) zigzag chain running along [100]. Adjacent chains are further connected by C-Hâ¯π and offset π-π inter-actions [centroid-centroid distance = 3.6572â (9)â Å], forming a double-chain structure. In the crystals of (II) and (III), mol-ecules are linked into chain structures by offset π-π inter-actions with centroid-centroid distances of 3.5349â (12) and 3.8845â (13)â Å for (II) and 3.588â (2)â Å for (III). In (II) and (III), the thio-phene rings are orientationally disordered over two sites, with occupancy ratios of 0.69:0.31 for (II), and 0.528â (4):0.472â (4) and 0.632â (5):0.368â (5) for (III).