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OBJECTIVE: Human Chorionic Gonadotropin (hCG) plays a crucial role in embryo implantation and in maintenance of pregnancy. An immuno-contraceptive approach involves the use of a recombinant hCGß-LTB vaccine formulated with adjuvant Mycobacterium indicus pranii (MIP), to prevent pregnancy without disturbing ovulation, hormonal profiles, and menstrual cycles in women. The present work in mice was designed to address issues encountered in clinical trials conducted with hCGß-LTB vaccine, with focus on two primary concerns. Firstly, it aimed to determine the optimal vaccine dosage required to induce a high level of anti-hCG antibodies. Secondly, it aimed to assess the safety profile of the vaccine, specifically injection site reactions in the form of nodules, observed in some of the subjects. METHODS AND RESULTS: Studies undertaken indicate that a 2 µg dose of the protein version of the vaccine, administered in mice through the intramuscular route, can induce high anti-hCG titres. Furthermore, administering a booster dose enhances the antibody response. Our findings suggest that the concentration and frequency of administration of the adjuvant MIP can also be reduced without compromising vaccine efficacy. CONCLUSION: The issue of nodule formation at the injection site can be mitigated either by administering the vaccine along with MIP intramuscularly or injecting hCG vaccine and MIP at separate intradermal sites. Thus, protein vaccine administered at a 2µg dose via the intramuscular route addresses both efficacy and safety concerns.
The Phase I/II clinical trials initiated with the recombinant hCG vaccine in women revealed inadequate antibody titres in all subjects, alongside the development of nodules at the injection sites in some participants. Studies were undertaken in mice to propose potential strategies for mitigating injection site reactions and enhancing the antibody response. It was concluded that the optimum dose of the protein version of the vaccine to get high antibody titres, is 2 µg administered intramuscularly while upholding safety standards.
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Gonadotropina Coriônica , Vacinas Sintéticas , Animais , Feminino , Camundongos , Vacinas Sintéticas/imunologia , Gonadotropina Coriônica/imunologia , Anticoncepção Imunológica/métodos , Vacinas Anticoncepcionais/imunologia , Formação de Anticorpos/efeitos dos fármacos , Humanos , Camundongos Endogâmicos BALB C , Adjuvantes Imunológicos , Reação no Local da Injeção , Engenharia Genética , Injeções Intramusculares , Gonadotropina Coriônica Humana Subunidade beta/imunologiaRESUMO
Deciphering the most promising strategy for the evolution of potential wound-healing therapeutics is one of the greatest challenging affairs to date. The development of peptide-based smart scaffolds with innate antimicrobial, anti-inflammatory, and antioxidant properties is an appealing way out. Aligned to the goal a set of Hydrogelators I-IV were developed utilizing the concept of chiral orchestration in diphenylalanine fragment, such that the most potent construct with all the bench marks namely mechanoresponsiveness, biocompatibility, consistent antimicrobial and antioxidant properties, could be fished out from the design. Interestingly, our inâ vitro Antifungal and Lipid peroxidation analysis identified the homochiral isomer Boc-δ-Ava-L-Phe-L-Phe-OH (Hydrogelator I), as an ideal candidate for the wound healing experiment, so we proceeded for the inâ vivo histopathological and antioxidant measurements in Wister rats. Indeed the wound images obtained from the different sets of animals on the 14th day of treatment demonstrated that with increased recovery time, hydrogelator I displayed a significant reduction in the lesion diameter compared to the marketed drug, and negative control. Even the histopathological measurements using H & E staining demonstrated diminished tissue destruction, neutrophil infiltration necrosis, and lymphatic proliferation in the hydrogelators, in comparison to others, backed by inâ vivo lipid peroxidation data. Overall our investigation certifies hydrogelator I as an effective therapeutic for managing the wound healing complication.
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Arthritis is a clinical condition, which mainly affects the structure and function joints. During this condition the joints gets swelled and stiffed resulting into development of pain and morbidity. Corticosteroids are frequently prescribed to manage various clinical conditions including the chronic inflammatory diseases such as arthritis. The steroidal drug also causes certain adverse effects depending on the dose, the route of administration and duration of treatment. However, a systematic investigation on the biochemical consequences of steroids as a therapeutic has not been carried out. In the present study we analyzed certain parameters associated to oxidative stress, liver function and energy metabolism has been done in the blood plasma of the arthritis patients who were using steroidal drugs (methylprednisolone and deflazacort) up to 168 days for the treatment of the disease. The results indicated increase in level of MDA and decrease in the activities of SOD, CAT and LDH. The activities of AST and ALT were found to be significantly enhanced over the increase in the treatment period. These results suggested that corticosteroids may induce lipid peroxidation, oxidative stress and liver toxicity in the arthritis patients in the dose and duration dependent manner. The use of antioxidants as supplements to the anti-arthritis agents could play a role in suppressing the oxidative stress mediated adverse effects. However, extensive research is required to explore for safer medication devoid of steroids to cure arthritis.
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The identification and pharmacological validation of plant-based lead compounds for the cure of different diseases including cancer have always been globally strived. In addition to possessing numerous medicinal properties, many of the phytochemicals display antioxidant potential activities. Reactive oxygen species (ROS) causeoxidative stress leading to several severe diseases such as cancer. The antioxidants are substances that fight against ROS to protect the cells from their damaging effects. In the present study, the effects of methanol extract of Euglena tuba(ETME) have been evaluated for its antioxidant and antitumor potential against Dalton's lymphoma (DL) introduced in BALB/cmice. After 24 h of intraperitoneal inoculation of DL cells in mice, ETME (300 mg kg-1 body weight) was administered intraperitoneally upto18 alternative days. On the 18th day, the mice were sacrificed; the blood and tissues (liver and brain) were collected to determine the tumor growth parameters including morphological, behavioural, haematological profile, and antioxidant indices. The results indicated that ETME exhibited significant antioxidative and antitumor properties when compared with the data from DL bearing mice. The results from the present study indicated that ETME contained remarkable antitumor efficacy, which was mediated through amelioration of oxidative stress. The data suggested that ETME could be used as a potential natural anticancer agent.
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An important research effort on the design of the magnetic particles is increasingly required to optimize the heat generation in biomedical applications, such as magnetic hyperthermia and heat-assisted drug release, considering the severe restrictions for the human body's exposure to an alternating magnetic field. Magnetic nanoparticles, considered in a broad sense as passive sensors, show the ability to detect an alternating magnetic field and to transduce it into a localized increase of temperature. In this context, the high biocompatibility, easy synthesis procedure and easily tunable magnetic properties of ferrite powders make them ideal candidates. In particular, the tailoring of their chemical composition and cation distribution allows the control of their magnetic properties, tuning them towards the strict demands of these heat-assisted biomedical applications. In this work, Co0.76Zn0.24Fe2O4, Li0.375Zn0.25Fe2.375O4 and ZnFe2O4 mixed-structure ferrite powders were synthesized in a 'dry gel' form by a sol-gel auto-combustion method. Their microstructural properties and cation distribution were obtained by X-ray diffraction characterization. Static and dynamic magnetic measurements were performed revealing the connection between the cation distribution and magnetic behavior. Particular attention was focused on the effect of Co2+ and Li+ ions on the magnetic properties at a magnetic field amplitude and the frequency values according to the practical demands of heat-assisted biomedical applications. In this context, the specific loss power (SLP) values were evaluated by ac-hysteresis losses and thermometric measurements at selected values of the dynamic magnetic fields.
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Cobalto/química , Compostos Férricos/química , Lítio/química , Nanopartículas de Magnetita/química , Zinco/química , Materiais Biocompatíveis/química , Pós/química , Temperatura , Difração de Raios XRESUMO
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the most common cause of severe neonatal thrombocytopenia and intracranial bleeding in term newborns. Intracranial hemorrhage (ICH) commonly results in death or severe, lasting neurologic disability. The timing of ICH is also important for management of the next affected pregnancy in cases of FNAIT. This manuscript reviews the advantages and disadvantages of the different radiologic methodologies to identify and characterize ICH. It discusses the limits of ultrasound and the advantages of magnetic resonance imaging allowing avoidance of the radiation associated with computed tomography (CT) scans.
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Doenças Fetais/diagnóstico por imagem , Hemorragias Intracranianas/diagnóstico por imagem , Trombocitopenia Neonatal Aloimune/diagnóstico por imagem , Trombocitopenia Neonatal Aloimune/terapia , Feminino , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Gravidez , Tomografia Computadorizada por Raios XRESUMO
In this study, we have co-loadedatorvastatin (ATR) and quercetin (QCT) in a nonionic microemulsion. After developing a derivative ratio spectrophotometric technique for simultaneous analysis of ATR and QCT, pseudoternary phase diagram was constructed utilizing1:4 d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and ethanol as surfactant and cosurfactant, respectively. Oleic acid was used as oil phase. Structural characterization of the formulation was carried out along a water dilution line created in monophasic region. Characterizations at these dilution points were performed using dynamic light scattering and polarized light microscopy. The average hydrodynamic size of the optimized formulation was found to be 18.9 nm and it did not change upon loading of ATR and QCT. In vitro release was assessed for the formulations loaded with different ratios of ATR and QCT, and the data were fitted to different mathematical models. Interestingly, we noticed differences in release kinetics during changes in dose ratios, particularly for QCT. Higuchi kinetics, observed at equal dose, shifted to Korsmeyer-Peppas model at higher QCT-ATR ratio (2:1 and 4:1). This difference is attributable to the ability of QCT molecules of overwhelming the interface at higher concentrations. Altogether, our observations highlight that the ratio of payloads should be selected carefully in order to avoid unpredictable release patterns.
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Quercetina , Tensoativos , Quercetina/química , Atorvastatina , Solubilidade , Tensoativos/química , Emulsões/químicaRESUMO
The issue of environmental contamination, particularly caused by the existence of heavy metal particles, is a major and widely recognized subject that receives substantial global attention. The remediation of Cu(II), Cd(II), Ni(II), and Pb(II) ionic metal particles from synthetic wastewater using chemically treated plant leaves of Ageratum conyzoides (TAC) as a biosorbent was investigated. The biosorption process was implemented utilizing a batch system, wherein several operational parameters were considered, including temperature, pH, agitation time, biosorbent dosage, and initial concentration of the metal ion. Langmuir, Freundlich, Temkin, and D-R isotherm models were used to evaluate equilibrium data. The analyzed parameter exhibits characteristics that were best fitted with the Langmuir isotherm. The observed biosorption capacities (qm) of Cu(II), Pb(II), Ni(II), and Cd(II) ions on the TAC were measured as 51.573, 30.49, 33.53, and 35.91 mg/g, respectively, at a temperature of 22 °C. The affinity sequence of these metal ions follows the order Cu(II) > Pb(II) > Ni(II) > Cd(II). The measured values for the biosorption free energy change (ΔG) of Cu(II), Pb(II), Cd(II), and Ni(II) metal ions ranged from -1.017 to -4.723, -1.368 to -3.612, -2.785 to -5.21, and -1.047 to -5.135 kJ/mol, respectively. The enthalpy (ΔH) for Cu(II), Pb(II), Cd(II), and Ni(II) were determined to be +19.33, +6.82, +14.83, and +38.07 kJ/mol, respectively. Similarly, the corresponding entropy changes (ΔS) for the same series of metal ions were recorded as +0.075, +0.064, +0.063, and +0.135 kJ/mol.K. The pseudo-second-order kinetic models yielded superior outcomes in comparison to the pseudo-first-order kinetic models. The findings of the experiment indicated that the TAC demonstrates favorable efficacy in extracting all four metal ions. Hence, the utilization of biomass derived from Ageratum conyzoides leaves has proven to be a viable and economically feasible approach for biosorption of all four metals.
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Biomassa , Chumbo , Termodinâmica , Poluentes Químicos da Água , Cinética , Adsorção , Poluentes Químicos da Água/química , Chumbo/química , Chumbo/metabolismo , Concentração de Íons de Hidrogênio , Metais Pesados/química , Cobre/química , Cádmio/metabolismo , Cádmio/química , Temperatura , Níquel/química , Biodegradação Ambiental , Íons , Purificação da Água/métodosRESUMO
OBJECTIVE: Evidence suggests that antibiotics are unnecessary in infants with transient tachypnea of the newborn (TTN) that are low-risk for early-onset sepsis. The aim was to reduce ampicillin and gentamicin days of therapy (DOT) in infants with suspected TTN by 10% within 12 months. STUDY DESIGN: We used the Model for Improvement to test interventions from August 2019 to September 2021 to decrease antibiotic utilization in low-risk infants with TTN. Interventions included the creation of an evidence-based clinical pathway, admission huddles, and prescriber audit and feedback. RESULTS: We reduced ampicillin and gentamicin use by 26% and 23%, respectively. In 123 infants with suspected TTN, we sequentially decreased starting antibiotics in this group from 71% to 41%, 13% and 0%. There were no cases of missed bacteremia. CONCLUSION: Creation of a multidisciplinary antimicrobial stewardship QI team and subsequent interventions were successful in safely reducing antibiotic use in infants with TTN.
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Antibacterianos , Taquipneia Transitória do Recém-Nascido , Recém-Nascido , Lactente , Humanos , Antibacterianos/uso terapêutico , Taquipneia Transitória do Recém-Nascido/tratamento farmacológico , Melhoria de Qualidade , Ampicilina/uso terapêutico , Gentamicinas/uso terapêuticoRESUMO
OBJECTIVES: Unplanned extubations (UEs) can be a frequent problem and are associated with adverse outcomes. This quality improvement initiative sought to reduce UEs from tube dislodgement in a level IV NICU utilizing methods applicable to other ICUs and performed with minimal monetary funds. METHODS: From January 2019 to July 2023, an interdisciplinary quality improvement team used the Model for Improvement and performed sequential interventions to improve the outcome measure of UEs per 100 ventilator days. Process measures included adherence to a modified, site-specific UE care bundle derived from the Solutions for Patient Safety network, whereas the number of endotracheal tube-related pressure injuries was used as a balancing measure. Statistical process control charts and established rules for special cause variation were applied to analyze data. RESULTS: Sequential interventions reduced the rate of UEs from a baseline of 2.3 to 0.6 UEs per 100 ventilator days. Greater than 90% adherence with the UE care bundle and apparent cause analysis form completion occurred since December 2020. There were no endotracheal tube-related pressure injuries. CONCLUSIONS: A sustained reduction in UEs was demonstrated. Leveraging a multidisciplinary team allowed for continuous UE analysis, which promoted tailored consecutive interventions. UE care bundle audits and the creation of a postevent debrief guide, which helped providers share a common language, were the most impactful interventions. Next steps include disseminating these interventions to other ICUs across our hospital enterprise. These low-cost interventions can be scalable to other NICUs and PICUs.
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Extubação , Unidades de Terapia Intensiva Neonatal , Intubação Intratraqueal , Melhoria de Qualidade , Humanos , Recém-Nascido , Pacotes de Assistência ao PacienteRESUMO
The wound recovery phenomenon remains as one of the long challenging concerns worldwide. In search of user-friendly dressing materials, in this report, we fabricated a rational combinatorial strategy utilizing stereogenic harmony in a triphenylalanine fragment and appending it to δ-amino valeric acid at the N-terminus (hydrogelators I-VII) such that a potential scaffold could be fished out from the design. Our investigations revealed that all the hydrogelators displayed not only excellent self-healing performance as well as high mechanical strength at physiological pH but also mechanical stress-triggered gel-sol-gel transition properties. The structural and morphological investigation confirmed the presence of ß-sheet-like assemblies stabilized by intermolecular H-bonding and π-π interactions. Moreover, these scaffolds showed substantial antibacterial as well as antifungal efficacy against common wound pathogens, i.e, four Gram-positive bacteria (Staphylococcus aureus, Streptococcus mutans, B. subtilis, E. fecalis), four Gram-negative bacteria (Escherichia coli, Klebsiella pneumonia, P. aerugonosa, Proteus spp.), and two fungal strains (C. albicans and A. niger). The manifestation of consistent antioxidant properties might be due to the enhancement of amphiphilicity in hydrogelators, which has led to the generation of reactive oxygen species (ROS) in a facile manner, a probable mechanism to damage the microbial membrane, the driving force behind the antimicrobial efficacy. Also, the constructs exhibited proteolytic resistance and remarkable biocompatibility toward mammalian cells. Thus, based on the above benchmarks, the homochiral hydrogelator IV was seived out from a pool of seven, and we proceeded toward its in vivo evaluation using full-thickness excisional wounds in Wister rats. The scaffolds also accentuated the re-epithelialization as well in comparison to the negative control, thereby facilitating the wound closure process in a very short span of time (10 days). Overall, our in vitro and in vivo analysis certifies hydrogelator IV as an ideal dressing material that might hold immense promise for future wound care management.
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Antibacterianos , Anti-Infecciosos , Ratos , Animais , Ratos Wistar , Antibacterianos/química , Staphylococcus aureus , Antioxidantes , MamíferosRESUMO
Neurodegenerative disorders (NDDs) are caused by progressive loss of functional neurons following the aggregation and fibrillation of proteins in the central nervous system. The incidence rate continues to rise alarmingly worldwide, particularly in aged population, and the success of treatment remains limited to symptomatic relief. Graphene nanomaterials (GNs) have attracted immense interest on the account of their unique physicochemical and optoelectronic properties. The research over the past two decades has recognized their ability to interact with aggregation-prone neuronal proteins, regulate autophagy and modulate the electrophysiology of neuronal cells. Graphene can prevent the formation of higher order protein aggregates and facilitate the clearance of such deposits. In this review, after highlighting the role of protein fibrillation in neurodegeneration, we have discussed how GN-protein interactions can be exploited for preventing neurodegeneration. A comprehensive understanding of such interactions would contribute to the exploration of novel modalities for controlling neurodegenerative processes.
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Grafite , Nanoestruturas , Doenças Neurodegenerativas , Humanos , Idoso , Grafite/química , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/prevenção & controle , AutofagiaRESUMO
This study examines the effect of surface oxygen groups upon ability of graphene oxide (GO) sheets in suppressing the fibrillation of lysozyme (LYZ). Graphite was oxidized using 6 and 8 wt equivalents of KMnO4, and as produced sheets were abbreviated as GO-06 and GO-08, respectively. Particulate characteristics of sheets were characterized by light scattering and electron microscopic techniques, and their interaction with LYZ was analysed by circular dichroism (CD) spectroscopy. After ascertaining acid-driven conversion of LYZ to fibrillary form, we have shown that the fibrillation of dispersed protein can be prevented by adding GO sheets. Inhibitory effect could be attributed to binding of LYZ over the sheets via noncovalent forces. A comparison between GO-06 and GO-08 samples showed superior binding affinity of the latter. Higher aqueous dispersibility and density of oxygenated groups in GO-08 sheets would have facilitated the adsorption of protein molecules, thus making them unavailable for aggregation. Pre-treatment of GO sheets with Pluronic 103 (P103, a nonionic triblock copolymer), caused reduction in the adsorption of LYZ. P103 aggregates would have rendered the sheet surface unavailable for the adsorption of LYZ. Based on these observations, we conclude that fibrillation of LYZ can be prevented in association with graphene oxide sheets.
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Grafite , Grafite/química , Muramidase/química , Água , PolímerosRESUMO
BACKGROUND: Tinospora cordifolia Miers. (TC) (Giloya/Guduchi) is a native Indian herb, reported for its wide array of medicinal activities including immunomodulatory activity. However, the exact pharmacological mechanism of TC as an immunomodulatory agent remains unclear. Central to this, to the best of our knowledge, no study has explored the immunoadjuvant potential of TC in response to the Japanese encephalitis (JE) vaccines. PURPOSE: The study aims to explore the immunoadjuvant potential of TC ethanolic extract in response to the JE vaccine and illustrates its potential mechanism of immunomodulation using an integrated approach of network pharmacology and in-vivo experimental study. STUDY DESIGN AND METHODS: Initially, the extract was prepared and the components of TC were identified through high-resolution liquid chromatography mass spectrometry (HR-LC/MS). The compounds were then screened for network pharmacology analysis. Next, the drug and disease targets were identified and the network was constructed using Cytoscape 3.7.2 to obtain different signalling pathways of TC in JEV. We then evaluated the immunoadjuvant potential of TC ethanolic extract in mice immunized with inactivated JE vaccine (SA-14-14-2 strain). BALB/c mice were supplemented with TC extract (30 and 100 mg/kg, i.g.), daily for 56 days, marked with immunization on 28th day of the study, by JE vaccine. Blood was collected for flow cytometry and haematological analysis (total and differential cell counts). The surface expression of immune-cell markers (CD3+, CD4+, CD19+, CD11c+, CD40+) were evaluated on day 0 (pre-immunization), day 14 and 28 post-immunization. Additionally, inflammatory cytokines (IFN-γ+/IL-17A+) were evaluated post-14 and 28 days of immunization. RESULTS: The HR-LC/MS analysis identified the presence of glycosides, terpenoids, steroids and alkaloids in the TC extract. Through network analysis, 09 components and 166 targets were obtained, including pathways that involve toll-like receptor signalling, pattern-recognition receptor signalling, cytokine receptor and cytokine mediated signalling, etc. The in-vivo results showed that preconditioning with TC ethanolic extract significantly elevated the haematological variables (leucocyte count) as well as the surface expression of CD markers (B and T cell subsets) on day 0 (pre-immunization), day 14 and 28 post-immunization. Furthermore, preconditioning of TC demonstrated a dose-dependant augmentation of immune cells (CD3+, CD4+, CD19+, CD11c+) and inflammatory cytokines (IFN-γ+/IL-17A+) on day 14 and 28 post-immunization when compared to vaccine alone group. CONCLUSION: Results showed that preconditioning with TC extract before immunization might play a potential role in enhancing the cell-mediated as well as humoral immunity. Altogether, the combinatorial approach of network pharmacology and in-vivo animal experimentation demonstrated the immunoadjuvant potential of TC in response to JEV vaccine.
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Vacinas contra Encefalite Japonesa , Tinospora , Camundongos , Animais , Tinospora/química , Interleucina-17 , Farmacologia em Rede , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Citocinas/metabolismo , Adjuvantes Imunológicos/farmacologia , ImunidadeRESUMO
Mutations in the epigenetic regulator and global transcriptional activator, E1A binding protein (EP300), is being increasingly reported in aggressive hematological malignancies including adult T-cell leukemia/lymphoma (ATLL). However, the mechanistic contribution of EP300 dysregulation to cancer initiation and progression are currently unknown. Independent inhibition of EP300 in human cells results in the differential expression of genes involved in regulating the cell cycle, DNA replication and DNA damage response. Nevertheless, specific function played by EP300 in DNA replication initiation, progression and replication fork integrity has not been studied. Here, using ATLL cells as a model to study EP300 deficiency and an p300-selective PROTAC degrader, degrader as a pharmacologic tool, we reveal that EP300-mutated cells display prolonged cell cycle kinetics, due to pronounced dysregulations in DNA replication dynamics leading to persistent genomic instability. Aberrant DNA replication in EP300-mutated cells is characterized by elevated replication origin firing due to increased replisome pausing genome-wide. We demonstrate that EP300 deficiency results in nucleolytic degradation of nascently synthesized DNA at stalled forks due to a prominent defect in fork stabilization and protection. This in turn results in the accumulation of single stranded DNA gaps at collapsed replication forks, in EP300-deficient cells. Inhibition of Mre11 nuclease rescues the ssDNA accumulation indicating a dysregulation in downstream mechanisms that restrain nuclease activity at stalled forks. Importantly, we find that the absence of EP300 results in decreased expression of BRCA2 protein expression and a dependency on POLD3-mediated error-prone replication restart mechanisms. The overall S-phase abnormalities observed lead to under-replicated DNA in G2/M that instigates mitotic DNA synthesis. This in turn is associated with mitotic segregation defects characterized by elevated micronuclei formation, accumulation of cytosolic DNA and transmission of unrepaired inherited DNA lesions in the subsequent G1-phase in EP300-deficient cells. We demonstrate that the DNA replication dynamics of EP300-mutated cells ATLL cells recapitulate features of BRCA-deficient cancers. Altogether these results suggest that mutations in EP300 cause chronic DNA replication stress and defective replication fork restart results in persistent genomic instability that underlie aggressive chemo-resistant tumorigenesis in humans.
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The second messenger cyclic adenosine monophosphate (cAMP) plays a pivotal role in axonal growth and guidance, but its downstream mechanisms remain elusive. In this study, we report that type II protein kinase A (PKA) is highly enriched in growth cone filopodia, and this spatial localization enables the coupling of cAMP signaling to its specific effectors to regulate guidance responses. Disrupting the localization of PKA to filopodia impairs cAMP-mediated growth cone attraction and prevents the switching of repulsive responses to attraction by elevated cAMP. Our data further show that PKA targets protein phosphatase-1 (PP1) through the phosphorylation of a regulatory protein inhibitor-1 (I-1) to promote growth cone attraction. Finally, we find that I-1 and PP1 mediate growth cone repulsion induced by myelin-associated glycoprotein. These findings demonstrate that the spatial localization of type II PKA to growth cone filopodia plays an important role in the regulation of growth cone motility and guidance by cAMP.
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Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/farmacologia , Cones de Crescimento/efeitos dos fármacos , Pseudópodes/efeitos dos fármacos , Pseudópodes/enzimologia , Animais , Cálcio/metabolismo , Proteína Quinase Tipo II Dependente de AMP Cíclico , Ativação Enzimática/efeitos dos fármacos , Humanos , Proteínas Associadas aos Microtúbulos/metabolismo , Modelos Biológicos , Glicoproteína Associada a Mielina/farmacologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Fosfoproteínas Fosfatases/antagonistas & inibidores , Fosforilação/efeitos dos fármacos , Proteína Fosfatase 1 , Transporte Proteico/efeitos dos fármacos , Proteínas/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , XenopusRESUMO
Raga todi, an Indian classical music raga is emerging as a therapeutic approach in mental health and well being. This study aims to assess the relationship of raga todi and state anxiety at the time of novel coronavirus spread across the globe. 30 young female adults of age 20-28 years were randomly assigned to experimental group and control group of 15 participants each to which a pre and post test of State Anxiety test of STAI-A was administered. Results stated that state anxiety is negatively correlated to the listening of raga todi. Thus, listening to raga todi could be useful in reducing the state anxiety level provoked by a stressful life event like the lethal coronavirus pandemic.
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This paper reports the design, development and characterization of a broadband, polarization insensitive metasurface absorber in planar, cylindrically bent and 90° dihedral surface geometry. Four metallic patches loaded with eight lumped resistors are used, which has been optimized numerically using CST MICROWAVE STUDIO, as a unit cell of developed metasurface absorber, to achieve 20 dB reflection reduction for 51.21% fractional bandwidth (13.42-22.66 GHz) under normal incidence with 0.12 [Formula: see text] thickness (where [Formula: see text] corresponds to lower operating frequency). The numerical findings are also verified analytically using equivalent circuit analysis, which exhibits very good agreement. Polarization-insensitive characteristics are achieved using fourfold rotation symmetry of the designed structure. The fabricated prototype of the designed absorber is experimentally characterized, using free space measurement method and ABmm vector network analyzer (VNA) system, and fairly good agreement with numerical-analytical findings are reported. The major novelty of this study is the design and development of a broadband (13.42-22.66 GHz), polarization insensitive metasurface absorber that provides 20 dB reflection reduction numerically as well as experimentally in the whole band, which to the author's knowledge has not been observed till now. Also, keeping in mind the radar stealth applications, first time we have demonstrated both numerically and experimentally, different geometrical shapes of conformal metasurfaces that can be practically used in actual scenario.
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Parthenium hysterophorus possesses certain allelochemicals responsible for their medicinal effects. The presence of oils, polyphenols, alkaloids, terpenes, pseudoguaianolides, and histamines in P. hysterophorus has been shown to exhibit medicinal properties. However, the systematic biomedical properties of this plant are still unexplored. The extracts of leaves, stem, and flower of P. hysterophorus, both at low and high temperatures (equivalent to boiling points of different solvents) were prepared. The extracts prepared in hexane, ethylacetate, methanol, and water were analyzed spectrophotometrically and colorimetrically and resolved on TLC for the presence of phytochemicals. The analyses of the free radical quenching potential of plant extracts were done by DPPH assay. The total antioxidant capacity was determined by phosphomolybdate assay and the ferric reducing antioxidant power (FRAP) assay was used to determine the reduction potential of the extracts. The spectrophotometric and qualitative analysis of plant extracts demonstrated the presence of alkaloids, terpenoids, carbohydrates, and cardiac glycosides. The occurrence of more than one Rf values for extracts determined by TLC indicated the presence of more than one phytochemical compound. The P. hysterophorus extracts contained strong antioxidant activity. These extracts exhibited strong antimicrobial activity against Staphylococcus epidermis, Salmonela typhi, Neisseria gonococci or gonococci, Citrobacter, and Shigella flexineri. The evaluation of the antimicrobial potential of P. hysterophorus extracts was done by the disc diffusion method. These extracts also showed significant inhibition against HIV-1 RT activity. The anti-HIV-1 RT activity was done using Roche Kit. The P. hysterophorus extracts displayed the presence of many phytochemicals with strong antioxidant, antimicrobial, and anti-HIV-1 RT properties.
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Alcaloides , Anti-Infecciosos , Asteraceae , HIV-1 , Alcaloides/análise , Anti-Infecciosos/análise , Anti-Infecciosos/farmacologia , Antioxidantes/química , Asteraceae/química , Compostos Fitoquímicos/análise , Extratos Vegetais/química , Folhas de Planta/químicaRESUMO
The pandemic of COVID-19 has arrested the life of 7.8 million people living on this earth. However, some people are more vulnerable to the risk of this deadly virus. The frailty of senior citizens put them at the top of this list. The past 6 months have not only presented a threat to their physical health but to mental health also. Although lockdown was necessary to check the spread of the coronavirus it culminated in an exponential rise in the problems of loneliness, anxiety, fear, helplessness, and depression. The present paper reviews the role of social networking sites, apps, and other digital platforms in saving and enriching the lives of the elderly, especially those who spent the lockdown alone and were devoid of a regular support system due to unavailability of transport and administrative restrictions on the movement of people. It also analyzes the efficiency of the virtual world in reducing their anxiety of being alone by connecting them with others and also make them feel empowered. The review is based on the online data collected about the insurgence in the percentage of elderly people using such platforms, recent studies analyzing the effects of the COVID 19 pandemic on senior citizens. Besides this personal telephonic discussions were conducted with some elderly people who spent their lockdown alone in their homes. The study was primarily focused on three objectives. Firstly it attempts to understand the ways in which senior citizens made use of social networking sites and various digital platforms for managing life better. Secondly, it analyses the process of adopting technology, and finally, it examined the width and depth of the impact technology created in their life and also the permanence of this change. The analysis clearly suggests an increase in the digital life of elderly people. The process moved in distinct stages from utter confusion to relative ease in using technology, thereby significantly reducing the loneliness, and bringing relatively stable change in the way they lead their life.