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1.
Nat Commun ; 14(1): 7059, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37923741

RESUMO

Coherent imaging techniques provide an unparalleled multi-scale view of materials across scientific and technological fields, from structural materials to quantum devices, from integrated circuits to biological cells. Driven by the construction of brighter sources and high-rate detectors, coherent imaging methods like ptychography are poised to revolutionize nanoscale materials characterization. However, these advancements are accompanied by significant increase in data and compute needs, which precludes real-time imaging, feedback and decision-making capabilities with conventional approaches. Here, we demonstrate a workflow that leverages artificial intelligence at the edge and high-performance computing to enable real-time inversion on X-ray ptychography data streamed directly from a detector at up to 2 kHz. The proposed AI-enabled workflow eliminates the oversampling constraints, allowing low-dose imaging using orders of magnitude less data than required by traditional methods.

2.
Sci Data ; 10(1): 449, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37438367

RESUMO

Tools available for reproducible, quantitative assessment of brain correspondence have been limited. We previously validated the anatomical fiducial (AFID) placement protocol for point-based assessment of image registration with millimetric (mm) accuracy. In this data descriptor, we release curated AFID placements for some of the most commonly used structural magnetic resonance imaging datasets and templates. The release of our accurate placements allows for rapid quality control of image registration, teaching neuroanatomy, and clinical applications such as disease diagnosis and surgical targeting. We release placements on individual subjects from four datasets (N = 132 subjects for a total of 15,232 fiducials) and 14 brain templates (4,288 fiducials), totalling more than 300 human rater hours of annotation. We also validate human rater accuracy of released placements to be within 1 - 2 mm (using more than 45,000 Euclidean distances), consistent with prior studies. Our data is compliant with the Brain Imaging Data Structure allowing for facile incorporation into neuroimaging analysis pipelines.


Assuntos
Imageamento por Ressonância Magnética , Neuroimagem , Humanos , Encéfalo/diagnóstico por imagem , Controle de Qualidade
3.
Inorg Chem ; 62(25): 9818-9826, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37310343

RESUMO

Understanding the effect of the local electrical field around the reaction center in enzymes and molecular catalysis is an important topic of research. Herein, we explored the electrostatic field exerted by the alkaline earth metal ions (M2+ = Mg2+, Ca2+, Sr2+, and Ba2+) around Fe in FeIII(Cl) complexes by experimental and computational investigations. M2+ coordinated dinuclear FeIII(Cl) complexes (12M) were synthesized and characterized by X-ray crystallography and different spectroscopic techniques. EPR and magnetic moment measurements exhibited the presence of high-spin FeIII centers in the 12M complexes. Electrochemical investigations revealed FeIII/FeII reduction potential values shifted anodically in 12M complexes compared to 1. Likewise, 2p3/2 and 2p1/2 peaks in the XPS data were found to shift positively in the 12M complexes, demonstrating that redox-inactive metal ions make FeIII more electropositive. However, nearly similar λmax values in the UV-vis spectra were observed in 1 and 12M complexes. The first-principles-based computational simulations further revealed the impact of M2+ on stabilizing 3d-orbitals of Fe. The distortion in Laplacian distribution (∇2ρ(r)) of electron density around M2+ also indicates the possibility of having Fe-M interactions in these complexes. The absence of a bond critical point between FeIII and M2+ ions in the 12M complexes indicates dominant through-space interaction between these metal centers. Experimental and computational studies collectively imply that the installation of internal electrostatic fields exerted by M2+ ions in 12M complexes alters the electronic structure of FeIII.

4.
BMJ Case Rep ; 15(9)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36113960

RESUMO

Periapical lesions of endodontic origin are caused by microbial infection of pulp. According to various studies, it is known that necrosis of pulp provides a favourable habitat for microbes to replicate and release various toxins into the periapical tissue leading to inflammation and formation of a periapical lesion. A variety of non-invasive methods to manage such lesions include conservative root canal treatment, aspiration-irrigation technique, decompression technique, calcium hydroxide therapy, lesion sterilisation and tissue repair therapy, and the apexum procedure. We present a case report describing non-surgical management of a large periapical lesion associated with a permanent central incisor displaying internal inflammatory resorption using platelet rich fibrin (PRF), bone graft and mineral trioxide aggregate (MTA).


Assuntos
Hidróxido de Cálcio , Fibrina Rica em Plaquetas , Humanos , Hidróxido de Cálcio/uso terapêutico , Durapatita , Tratamento do Canal Radicular
5.
Biologia (Bratisl) ; 77(10): 2989-3000, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35814925

RESUMO

Banana sap is currently designated as a waste subsequent to utilization of pseudo stem in pulp and paper industry as well as other applications which is contributing to the environmental pollution. In the present study, banana sap and its crude extracts were evaluated for antimicrobial, antioxidant and anticancer properties. The role of oxidized and un-oxidized banana sap for its antimicrobial potential against a microbial test panel comprising gram positive as well as gram negative bacteria and Candida albicans using in vitro micro broth dilution assay. The un-oxidized banana sap exhibited a significantly higher antibacterial potential as evident by a lower minimal inhibitory concentration (MIC) ranging between 15.625 to 62.5 mg/mL. In vitro radical scavenging activity of dichloromethane (DCM) extract of banana sap by DPPH method exhibited 54.62 ± 1.09 (µg/mL) IC50 value at the concentration of 1 mg/mL. Dichloromethane extract of banana sap showed maximum cytotoxic effect with human breast cancer (MCF-7) cell proliferation at the concentration of 100 µg/mL which was 78.37 ± 0.05% and the cytotoxic effect significantly increased with increasing concentration of banana sap extract. Furthermore, LCMS studies revealed the presence of bioactive compounds in dichloromethane extract of banana sap, such as rescinnamine derivative, dihydrorescinnamine and epimedin A. The present study suggested that banana sap is a promising source of bioactive compounds with relevant antimicrobial, antioxidant and anticancer properties.

6.
Inorg Chem ; 61(7): 3152-3165, 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35119860

RESUMO

Two molecular copper(II) complexes, (NMe4)2[CuII(L1)] (1) and (NMe4)2[CuII(L2)] (2), ligated by a N2O2 donor set of ligands [L1 = N,N'-(1,2-phenylene)bis(2-hydroxy-2-methylpropanamide), and L2 = N,N'-(4,5-dimethyl-1,2-phenylene)bis(2-hydroxy-2-methylpropanamide)] have been synthesized and thoroughly characterized. An electrochemical study of 1 in a carbonate buffer at pH 9.2 revealed a reversible copper-centered redox couple at 0.51 V, followed by two ligand-based oxidation events at 1.02 and 1.25 V, and catalytic water oxidation at an onset potential of 1.28 V (overpotential of 580 mV). The electron-rich nature of the ligand likely supports access to high-valent copper species on the CV time scale. The results of the theoretical electronic structure investigation were quite consistent with the observed stepwise ligand-centered oxidation process. A constant potential electrolysis experiment with 1 reveals a catalytic current density of >2.4 mA cm-2 for 3 h. A one-electron-oxidized species of 1, (NMe4)[CuIII(L1)] (3), was isolated and characterized. Complex 2, on the contrary, revealed copper and ligand oxidation peaks at 0.505, 0.90, and 1.06 V, followed by an onset water oxidation (WO) at 1.26 V (overpotential of 560 mV). The findings show that the ligand-based oxidation reactions strongly depend upon the ligand's electronic substitution; however, such effects on the copper-centered redox couple and catalytic WO are minimal. The energetically favorable mechanism has been established through the theoretical calculation of stepwise reaction energies, which nicely explains the experimentally observed electron transfer events. Furthermore, as revealed by the theoretical calculations, the O-O bond formation process occurs through a water nucleophilic attack mechanism with an easily accessible reaction barrier. This study demonstrates the importance of redox-active ligands in the development of molecular late-transition-metal electrocatalysts for WO reactions.

7.
Inorg Chem ; 60(23): 18006-18016, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34813300

RESUMO

A mononuclear manganese(V) oxo complex of a bis(amidate)bis(alkoxide) ligand, (NMe4)[MnV(HMPAB)(O)] [2; H4HMPAB = 1,2-bis(2-hydroxy-2-methylpropanamido)benzene], was synthesized and structurally characterized. A Mn-Oterm distance of 1.566(4) Å was observed in the solid-state structure of 2, consistent with the Mn≡O formulation. The reaction of redox-inactive metal ions (Mn+ = Li+, Ca2+, Mg2+, Y3+, and Sc3+) with 2 resulted in the formation of 2-Mn+ species, which were characterized by UV-vis, 1H NMR, cyclic voltammetry, and in situ IR spectroscopy. Theoretical calculations suggested that the alkoxide oxygen atoms of the ligand scaffold are energetically most favorable for coordinating the Mn+ ions in 2. Complex 2 revealed one-electron-reduction potential at -0.01 V versus ferrocenium/ferrocene, which shifted anodically upon coordination of Mn+ ions to 2, and such a shift became more prominent with stronger Lewis acids. The oxygen-atom transfer (OAT) reactivities of 2 and 2-Mn+ species with triphenylphosphine were compared, which exhibited a systematic increase of the reaction rate with increasing Lewis acidity of Mn+ ions, and a plot of log k2 versus Lewis acidity of Mn+ ions (ΔE) followed a linear relationship. It was observed that 2-Sc3+ was ca. 3200 times more reactive toward the OAT reaction compared to 2. Hammett analysis of 2 exhibited a V-shaped plot, indicating a change of the reaction mechanism upon going from electron-rich to electron-deficient Ar3P substrates. In contrast, 2-Ca2+ and 2-Sc3+ showed an electrophilic nature toward the OAT reaction, thus demonstrating the role of the Lewis acid in controlling the OAT mechanism. The hydrogen-atom abstraction reaction of 2 and 2-Mn+ adducts with 1-benzyl-1,4-dihydronicotinamide was investigated, and it was observed that the rate of reaction did not vary considerably with the Lewis acidity of Mn+ ions. On the basis of Eyring analysis of 2 and 2-Mn+ adducts, we hypothesized an entropy-controlled hydrogen-atom-transfer reaction for 2-Sc3+, which is different from the reaction mechanism of 2 and 2-Ca2+.

8.
Chem Sci ; 12(12): 4418-4424, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-34163706

RESUMO

A terminal FeIIIOH complex, [FeIII(L)(OH)]2- (1), has been synthesized and structurally characterized (H4L = 1,2-bis(2-hydroxy-2-methylpropanamido)benzene). The oxidation reaction of 1 with one equiv. of tris(4-bromophenyl)ammoniumyl hexachloroantimonate (TBAH) or ceric ammonium nitrate (CAN) in acetonitrile at -45 °C results in the formation of a FeIIIOH ligand radical complex, [FeIII(L˙)(OH)]- (2), which is hereby characterized by UV-visible, 1H nuclear magnetic resonance, electron paramagnetic resonance, and X-ray absorption spectroscopy techniques. The reaction of 2 with a triphenylcarbon radical further gives triphenylmethanol and mimics the so-called oxygen rebound step of Cpd II of cytochrome P450. Furthermore, the reaction of 2 was explored with different 4-substituted-2,6-di-tert-butylphenols. Based on kinetic analysis, a hydrogen atom transfer (HAT) mechanism has been established. A pK a value of 19.3 and a BDFE value of 78.2 kcal/mol have been estimated for complex 2.

9.
10.
J Educ Health Promot ; 8: 171, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31867356

RESUMO

BACKGROUND: Advances in scientific research necessitates updating of the curriculum and the Medical Council of India now Board of Governors have proposed a new competency-based undergraduate curriculum for the Indian Medical Graduate. The authors wanted the views of medical students about basic sciences teaching in the form of feedback, their perceptions and attitudes toward the basic sciences and their opinions about the relevance of these subjects, and finally any ideas about improvement in teaching of basic sciences. MATERIALS AND METHODS: The present cross-sectional study was conducted in two medical colleges of Northern India and 250 medical students from each medical school were the study participants. Students of the 1st year were not included, but interns were included. A pretested questionnaire having twenty questions with answers in the form of "yes" and "no" was used. Chi-square was the test of significance. RESULTS: Almost all the participants considered the basic sciences as an integral part of medical curriculum and a higher number of Government Medical College respondents opined that their knowledge made it easier to understand clinical subjects (P < 0.05). However, higher proportion of ASCOMS (Acharya Shri Chandra College Medical Sciences) of respondents emphasized that the focus should be on clinical subjects and that current student-teacher ratio be increased (P < 0.05). Majority of the respondents labeled Anatomy having the immense syllabus, while Physiology was designated as more relevant and having a better recall during clinical discourse (P > 0.05). CONCLUSION: Basic sciences lay strong foundation for subsequent clinical learning. Medical education is best taught with hybrid use of lectures, tutorial, group discussions, audio-visual aids, and integrated teaching. The new proposed competency-based curriculum and the Attitudes, Ethics and Communication Module are likely to improve the overall medical education and health-care scenario.

11.
Hum Brain Mapp ; 40(14): 4163-4179, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31175816

RESUMO

Accurate spatial correspondence between template and subject images is a crucial step in neuroimaging studies and clinical applications like stereotactic neurosurgery. In the absence of a robust quantitative approach, we sought to propose and validate a set of point landmarks, anatomical fiducials (AFIDs), that could be quickly, accurately, and reliably placed on magnetic resonance images of the human brain. Using several publicly available brain templates and individual participant datasets, novice users could be trained to place a set of 32 AFIDs with millimetric accuracy. Furthermore, the utility of the AFIDs protocol is demonstrated for evaluating subject-to-template and template-to-template registration. Specifically, we found that commonly used voxel overlap metrics were relatively insensitive to focal misregistrations compared to AFID point-based measures. Our entire protocol and study framework leverages open resources and tools, and has been developed with full transparency in mind so that others may freely use, adopt, and modify. This protocol holds value for a broad number of applications including alignment of brain images and teaching neuroanatomy.


Assuntos
Encéfalo/anatomia & histologia , Marcadores Fiduciais , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Humanos
12.
Indian J Med Res ; 145(4): 471-478, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28862178

RESUMO

BACKGROUND & OBJECTIVES: Prenatal diagnosis of malformations is an important method of prevention and control of congenital anomalies with poor prognosis. Central nervous system (CNS) malformations amongst these are the most common. The information about the prevalence and spectrum of prenatally detected malformations is crucial for genetic counselling and policymaking for population-based preventive programmes. The objective of this study was to study the spectrum of prenatally detected CNS malformations and their association with chromosomal abnormalities and autopsy findings. METHODS: This retrospective study was conducted in a tertiary care hospital in north India from January 2007 to December 2013. The details of cases with prenatally detected CNS malformations were collected and were related with the foetal chromosomal analysis and autopsy findings. RESULTS: Amongst 6044 prenatal ultrasonographic examinations performed; 768 (12.7%) had structural malformations and 243 (31.6%) had CNS malformations. Neural tube defects (NTDs) accounted for 52.3 per cent of CNS malformations and 16.5 per cent of all malformations. The other major groups of prenatally detected CNS malformations were ventriculomegaly and midline anomalies. Chromosomal abnormalities were detected in 8.2 per cent of the 73 cases studied. Foetal autopsy findings were available for 48 foetuses. Foetal autopsy identified additional findings in eight foetuses and the aetiological diagnosis changed in two of them (4.2%). INTERPRETATION & CONCLUSIONS: Amongst prenatally detected malformations, CNS malformations were common. NTD, which largely is a preventable anomaly, continued to be the most common group. Moreover, 60 per cent of malformations were diagnosed after 20 weeks, posing legal issues. Chromosomal analysis and foetal autopsy are essential for genetic counselling based on aetiological diagnosis.


Assuntos
Sistema Nervoso Central/patologia , Malformações do Sistema Nervoso/diagnóstico , Defeitos do Tubo Neural/diagnóstico , Diagnóstico Pré-Natal , Autopsia , Aberrações Cromossômicas , Feminino , Feto , Aconselhamento Genético , Testes Genéticos , Humanos , Índia , Malformações do Sistema Nervoso/classificação , Malformações do Sistema Nervoso/genética , Malformações do Sistema Nervoso/patologia , Tubo Neural/patologia , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/patologia , Gravidez
13.
Sci Rep ; 6: 31649, 2016 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-27535180

RESUMO

The ratio of ω-6 to ω-3 polyunsaturated fatty acids (PUFAs) appears to be critical in the regulation of various pathophysiological processes and to maintain cellular homeostasis. While a high proportion of dietary intake of ω-6 PUFAs is associated with various inflammatory disorders, higher intake of ω-3 PUFAs is known to offer protection. It is now well established that beneficial effects of ω-3 PUFAs are mediated in part by their oxygenated metabolites mainly via the lipoxygenase (LOX) and cyclooxygenase (COX) pathways. However, the down-stream signaling pathways that are involved in these anti-inflammatory effects of ω-3 PUFAs have not been elucidated. The present study evaluates the effects of 15-LOX metabolites of α-linolenic acid (ALA, ω-3 PUFA) on lipopolysaccharide (LPS) induced inflammation in RAW 264.7 cells and peritoneal macrophages. Further, the effect of these metabolites on the survival of BALB/c mice in LPS mediated septic shock and also polymicrobial sepsis in Cecal Ligation and Puncture (CLP) mouse model was studied. These studies reveal the anti-inflammatory effects of 13-(S)-hydroperoxyoctadecatrienoic acid [13-(S)-HPOTrE] and 13-(S)-hydroxyoctadecatrienoic acid [13-(S)-HOTrE] by inactivating NLRP3 inflammasome complex through the PPAR-γ pathway. Additionally, both metabolites also deactivated autophagy and induced apoptosis. In mediating all these effects 13-(S)-HPOTrE was more potent than 13-(S)-HOTrE.


Assuntos
Araquidonato 15-Lipoxigenase/metabolismo , Inflamassomos/metabolismo , Macrófagos Peritoneais/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Choque Séptico/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Ácido alfa-Linolênico/farmacologia , Animais , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Macrófagos Peritoneais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células RAW 264.7 , Choque Séptico/induzido quimicamente , Choque Séptico/metabolismo , Choque Séptico/patologia , Ácido alfa-Linolênico/metabolismo
14.
Sci Rep ; 5: 18362, 2015 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-26670139

RESUMO

Innate immunity of the corneal epithelium is conferred by proteinaceous secretions from the epithelium and associated lacrimal and meibomian glands. Lacritin, an eye-specific protein with anti-microbial, cytoprotective and wound-healing properties, predominantly secreted by lacrimal glands, is absent in conditions such as Dry eye and Keratitis. In view of the biological significance of lacritin in human eye, we investigated its role in human corneal epithelial (HCE) cells during lipopolysaccharide (LPS)-induced infection. LPS-challenged HCE cells demonstrated apoptosis-mediated cell death and elevated lacritin levels. The LPS-induced cell death is alleviated with exogenous supplementation of recombinant lacritin. This cytoprotective effect of lacritin is mediated through Cyclooxygenase-2 (COX-2). This study is the first to highlight the protective role of lacritin and mechanism of its action during bacterial infection of cornea in vitro.


Assuntos
Células Epiteliais/metabolismo , Epitélio Corneano/metabolismo , Glicoproteínas/metabolismo , Lipopolissacarídeos/toxicidade , Morte Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Síndromes do Olho Seco/metabolismo , Síndromes do Olho Seco/patologia , Células Epiteliais/patologia , Epitélio Corneano/patologia , Humanos , Ceratite/metabolismo , Ceratite/patologia
15.
Dalton Trans ; 44(19): 8932-7, 2015 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-25873179

RESUMO

The syntheses of three polynuclear heterobimetallic complexes through the use of a homoleptic mercuric thiolate anion as a template for the assembly of coinage metal are presented. The complexes, [(PPh3)3Ag3(µ-SPh)7Hg2] (1), [Hg(µ-SPh)4{Cu(PPh3)2}2] (2) and [(dppe)2Cu5(µ-SPh)7Hg2(SPh)2] (3) were utilized as precursors for the fabrication of Hg-Ag and Hg-Cu intermetallics.

16.
BMC Complement Altern Med ; 14: 319, 2014 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-25169718

RESUMO

BACKGROUND: Plants are the valuable source of natural products with important medicinal properties. Most of the approved anti cancer drugs have a natural product origin or are natural products. Retinoblastoma is the most common ocular cancer of children. Although chemotherapy is the preferred mode of therapy, a successful treatment for retinoblastoma requires enucleation. Chebulagic acid (CA) from Terminalia chebula was shown to have anti-proliferative properties in the studies on cancerous cell lines. Due to anti cancer properties of CA and due to limitation in treatment options for retinoblastoma, the present study is undertaken to understand the role of CA on the proliferation of retinoblastoma cells. METHODS: Anti proliferative potential of CA was determined by MTT assay. The expression levels of various cell death mediators in retinoblastoma cells with CA treatment were assessed by Western blotting. Flowcytometer analysis was used to estimate the mitochondrial membrane potential (MMP) and to determine the percentage of cells undergoing apoptosis. RESULTS: The present study showed CA inhibited the proliferation of retinoblastoma cells in a dose dependent manner. CA modulated MMP, induced release of Cytochrome c, activated caspase 3 and shifted the ratio of BAX and Bcl2 towards cell death. G1 arrest, noticed in CA treated cells, is mediated by the increase in the expression of CDK inhibitor p27. CA treatment also decreased the levels of NFκB in the nucleus. This decrease is mediated by suppression in degradation of IκBα. CONCLUSION: CA has shown significant anti proliferative potential on retinoblastoma cells. Our findings clearly demonstrate that CA induces G1 arrest, inhibits NFκB and induces apoptosis of retinoblastoma cells.


Assuntos
Apoptose/efeitos dos fármacos , Benzopiranos/farmacologia , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Glucosídeos/farmacologia , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Retinoblastoma/patologia , Terminalia/química , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocromos c/metabolismo , Humanos , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , Retinoblastoma/tratamento farmacológico , Retinoblastoma/genética , Retinoblastoma/metabolismo
17.
Toxicol In Vitro ; 27(8): 2242-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24055895

RESUMO

Pyrethroids including allethrin are the most common commercial household insecticides. The detrimental effects caused by pyrethroids on humans are gaining considerable attention. The present study was aimed to elucidate the effects of allethrin on the human corneal epithelial (HCE) cells. Allethrin inhibited the proliferation of HCE cells in a dose-dependent manner. In the presence of allethrin, cells showed membrane blebbing and nuclear fragmentation along with significant decrease in mitochondrial membrane potential resulting in increased cytochrome c (Cyt c) release into the cytosol. Further, flow cytometry analysis demonstrated a marked increase in sub G0-G1 cells, characteristic of apoptosis. Increased expression of pro-apoptotic protein, Bax, a simultaneous decrease of anti-apoptotic protein, Bcl-2, and activation of Caspase 3 was evident in the treated cells. In addition, extracellular matrix digesting metalloproteinase 9 (MMP-9) was also stimulated. Furthermore, significant increase in the gene expression of inflammatory cytokines, TNF-α and IL-1ß was observed. Taken together, these findings suggest that allethrin (IC50≈85µM) is toxic to HCE cells causing death through mitochondrial pathway.


Assuntos
Aletrinas/toxicidade , Células Epiteliais/efeitos dos fármacos , Epitélio Corneano/citologia , Inseticidas/toxicidade , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Células Epiteliais/metabolismo , Humanos , Interleucina-1beta/genética , Metaloproteinase 9 da Matriz/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/genética , Proteína X Associada a bcl-2/metabolismo
18.
R I Med J (2013) ; 96(5): 43-7, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23641464

RESUMO

UNLABELLED: Little is known about lifestyle choices and preventive healthcare seeking behaviors among resident physicians. Residents function under unusual working conditions requiring extensive duty hours. This may significantly affect attentiveness to personal health and wellness. In this study, we surveyed residents across multiple training programs to compare lifestyle choices and access to preventive healthcare. METHODS: Resident physicians affiliated with Brown University, Providence, Rhode Island, were surveyed between February and April 2009 regarding lifestyle habits and experiences with primary care. We evaluated the relationships between training program and established primary care on health behaviors. RESULTS: Residents were in one of 5 programs: internal medicine, medicine/pediatrics, emergency medicine, surgery or pediatrics. Respondents slept an average of 6.7 hours per day and worked an average of 70 hours per week, with surgical residents sleeping the shortest and working the longest hours (p<0.001 for both). An average of 58.8% of residents indicated having a primary care physician. This rate was lowest among surgery residents at 37% (p=0.081). Rates of screening with regards to blood pressure, cholesterol and cervical cancer were significantly higher among residents maintaining primary care (p<0.001). A lack of time was the most common barrier to obtaining primary care. DISCUSSION: Surgical residents may have unique barriers to healthcare seeking behaviors, such as longer work hours. Residents with established primary care had significantly higher rates of adherence to preventive screening. Residency programs should address barriers to accessing healthcare for trainees, particularly among surgical programs.


Assuntos
Atitude do Pessoal de Saúde , Comportamentos Relacionados com a Saúde , Internato e Residência , Médicos , Adulto , Consumo de Bebidas Alcoólicas , Pressão Sanguínea , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Médicos/psicologia , Atenção Primária à Saúde , Rhode Island , Sono , Fumar , Transtornos Relacionados ao Uso de Substâncias , Carga de Trabalho
19.
J Ethnopharmacol ; 141(3): 989-96, 2012 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-22484053

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cissus quadrangularis is an ancient medicinal plant. It is an active ingredient of one Ayurvedic formula called "Laksha Gogglu". Its stem is used in food preparation in India. Traditionally it is used to treat various diseases like asthma, indigestion, ear diseases, irregular menstruation, skin diseases, piles, fractured bones, etc. AIM OF THE STUDY: This study aimed to evaluate the ability of the plant extracts to inhibit cycloxygenase (COX-1), cycloxygenase (COX-2), and 5-lipoxygenase (5-LOX) enzyme activity. Western blot analysis was also carried out in the quest to determine the effect of active acetone fraction of Cissus quadrangularis (AFCQ) on proinflammatory mediators as acetone extract is found to be the most effective in this study. MATERIALS AND METHODS: The differential extract of the stem were tested for enzyme inhibition of COX and 5-LOX using spectroscopic and polarigraphic method. Effective acetone extract was partially purified by silica column, one of the active fraction showed dual inhibition against COX and 5-LOX. Western blotting shows downregulation of proinflammatory mediators as well as upregulation of phase-II enzymes. RESULTS: AFCQ extract showed COX and 5-LOX inhibition with IC(50) values of 7 µg/ml, 0.4 µg/ml, and 20 µg/ml for COX-1, COX-2 and 5-LOX respectively. It also showed anti-inflammatory activity on RAW 264.7 cell line with IC(50) value 65 µg/ml. In addition to this it is showing inhibition of proinflammatory mediators like iNOS and TNFα, along with translocation of Nrf-2 and upregulation of HO-1. CONCLUSION: AFCQ is a COX and 5-LOX inhibitor isolated from the stems of Cissus quadrangularis. It is also effectively downregulate the iNOS, TNFα, and upregulation of HO-1.


Assuntos
Anti-Inflamatórios/farmacologia , Cissus , Inibidores de Ciclo-Oxigenase/farmacologia , Inibidores de Lipoxigenase/farmacologia , Extratos Vegetais/farmacologia , Animais , Araquidonato 5-Lipoxigenase/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo
20.
Toxicol In Vitro ; 26(3): 396-405, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22245431

RESUMO

Gallic acid (GA) induces apoptosis in various cancer cell lines. In this study, we investigated the apoptotic activity induced by GA on chronic myeloid leukemia (CML) cell line-K562 and the underlying mechanism. GA reduced the viability of K562 cells in a dose and time dependent manner. GA led to G0/G1 phase arrest in K562 cells by promoting p21 and p27 and inhibiting the levels of cyclin D and cyclin E. Further studies indicated apoptosis with impaired mitochondrial function as a result of deranged Bcl-2/Bax ratio, leakage of cytochrome c and PARP cleavage along with DNA fragmentation and by up-regulating the expression of caspase-3. GA also activated the protein expressions of fatty acid synthase ligand and caspase-8. GA is more effective in imatinib resistant-K562 (IR-K562) cells (IC50 4 µM) than on K562 cells (IC50 33 µM). GA inhibited cyclooxygenase-2 (COX-2) in K562 as well as IR-K562 cells appears to be COX-2 involved in the suppression of growth. Interestingly, GA also inhibited BCR/ABL tyrosine kinase and NF-κB. In conclusion, GA induced apoptosis in K562 cells involves death receptor and mitochondrial-mediated pathways by inhibiting BCR/ABL kinase, NF-κB activity and COX-2.


Assuntos
Antineoplásicos/farmacologia , Ácido Gálico/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Benzamidas , Ciclo-Oxigenase 2/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Ácido Gálico/administração & dosagem , Humanos , Mesilato de Imatinib , Concentração Inibidora 50 , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/farmacologia
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