RESUMO
Employee wellbeing as a central aspect of organizational growth has been widely regarded and accepted. Therefore, a considerable growth in the number of researches focusing on employee wellbeing has been comprehended in recent years. Employee wellbeing characterizes the individual's own cognitive interpretation of his/her life at work. The present study made an attempt to examine how workplace spirituality, empathic concern and organizational politics influences employee wellbeing. It was hypothesized that empathic concern mediates the relationship between workplace spirituality and employee wellbeing while organizational politics act as a moderator in this relationship. A survey was conducted on 253 employees working in Uttar Pradesh Police department (Uttar Pradesh, India). The results obtained revealed that workplace spirituality, empathic concern and employee wellbeing carries a positive association among them whereas these variables were found to be negatively correlated with organizational politics. Results also depicted that empathic concern significantly mediates between workplace spirituality and employee wellbeing. Further, moderated mediation analysis confirmed employee wellbeing as a function of workplace spirituality, empathic concern and organizational politics. The present study has put forward several practical implications for business practitioners and research directions for academicians, emphasizing upon the need to investigate the comprehensive impact of employee wellbeing in organization and the society as a whole.
RESUMO
Soil biotechnology (SBT) is a green engineering approach for wastewater treatment and recycling. Five SBT units located in the Mumbai region were under consideration of which holistic assessment of two SBT plants was carried out considering its technical, environmental and economic aspects and was compared with published research of other three. LCA has been done to evaluate the environmental impacts of construction and operation phase of SBT. Chemical oxygen demand (COD) and biochemical oxygen demand (BOD) removal of more than 90% can be achieved using this technology. Also, the nutrient removal proficiency (nitrate, nitrite, ammoniacal nitrogen, TKN, total nitrogen and phosphates) of this technique is good. On the other hand, SBT has low annual operation and maintenance cost, comparable to land-based systems and lower than conventional or advanced technologies. From the life cycle impact assessment, the main contributors for overall impact from the plant were identified as electricity consumption, discharges of COD, P-PO43- and N-NH4+ and disposal of sludge. The construction phase was found to have significantly more impact than the operation phase of the plant. This study suggests plant I is not relatively as efficient enough regarding sanitation. SBT provides several benefits over other conventional technologies for wastewater treatment. It is based on a bio-conversion process and is practically maintenance free. It does not produce any odorous bio-sludge and consumes the least energy.
Assuntos
Solo , Águas Residuárias , Biotecnologia , Higiene , Eliminação de Resíduos LíquidosRESUMO
In present study a series of triazolopyrimidine-quinoline and cyanopyridine-quinoline hybrids were designed, synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs). Molecular docking and scoring was utilized for the design of inhibitors. The molecules were synthesized via an easily accessible, convergent synthetic route. Three triazolopyrimidine based compounds showed nanomolar activity towards acetylcholinesterase. Among them, Ethyl 6-fluoro-4-(4-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)piperazin-1-yl)quinoline-3-carboxylate (10d), strongly inhibited AChE with IC50 value of 42 nM. Furthermore compound 10d was identified as most promising compound with 12 fold selectivity against butyrylcholinesterase (BuChE). This compound displayed a composed multitargeted profile with promising inhibition of self-induced and AChE - induced Aß aggregation and antioxidant activity.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Antioxidantes/síntese química , Antioxidantes/farmacologia , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/farmacologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Peptídeos beta-Amiloides/química , Animais , Antioxidantes/farmacocinética , Antioxidantes/uso terapêutico , Butirilcolinesterase/química , Butirilcolinesterase/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Química Sintética , Inibidores da Colinesterase/farmacocinética , Inibidores da Colinesterase/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Humanos , Cinética , Simulação de Acoplamento Molecular , Fragmentos de Peptídeos/química , Agregados Proteicos/efeitos dos fármacos , Conformação Proteica , Pirimidinas/farmacocinética , Pirimidinas/uso terapêuticoRESUMO
Induction of regulatory T cells (Treg) is an important mechanism leading to tolerance against tumors. Increased levels of Treg have been described in renal cell carcinoma (RCC) patients and seem to correlate with an adverse outcome. Our study aimed to analyze the influence of sorafenib and sunitinib on the frequency of Treg in patients with metastatic RCC (mRCC). Treg were analyzed by flow cytometry in the peripheral blood (PB) of patients (n=19) with histologically confirmed mRCC under treatment with either sunitinib (50 mg/d, n=11) or sorafenib (800 mg/d, n=8). Blood samples were taken before treatment and during the first, second, and third months of therapy. Flow cytometric analysis of PB mononuclear cells was performed using fluorochrome-labeled antibodies against CD3, CD4, CD25, and FOXp3. During the first month of therapy, patients treated with sorafenib showed a significant increase in FOXp3CD3CD4CD25 Treg (13.5 vs. 36.3% of gated cells, P=0.02, or 0.35 vs. 0.49% of total cells) and the ratio FOXp3 T cells/FOXp3 T cells (0.16 vs. 0.56 of gated cells, P=0.02). These elevated levels persisted throughout the treatment period. There was no influence of sunitinib on the frequency of Treg in our cohort of patients. Sorafenib, but not sunitinib, leads to an early and sustained increase in Treg in PB of mRCC patients. In immunoresponsive tumors such as RCC, immunological effects of kinase inhibitors are particularly relevant for the design of combination trials with immunotherapeutic agents. Our study suggests that sorafenib should be avoided in such a therapeutic setting.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Pirróis/uso terapêutico , Linfócitos T Reguladores/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Complexo CD3/metabolismo , Antígenos CD4/metabolismo , Carcinoma de Células Renais/patologia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Niacinamida/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Sorafenibe , Sunitinibe , Linfócitos T Reguladores/metabolismo , Resultado do TratamentoRESUMO
Mutations in the coactivator CREB-binding protein (CBP) are a major cause of the human skeletal dysplasia Rubinstein-Taybi syndrome (RTS); however, the mechanism by which these mutations affect skeletal mineralization and patterning is unknown. Here, we report the identification of 3-phosphoinositide-dependent kinase 1 (PDK1) as a key regulator of CBP activity and demonstrate that its functions map to both osteoprogenitor cells and mature osteoblasts. In osteoblasts, PDK1 activated the CREB/CBP complex, which in turn controlled runt-related transcription factor 2 (RUNX2) activation and expression of bone morphogenetic protein 2 (BMP2). These pathways also operated in vivo, as evidenced by recapitulation of RTS spectrum phenotypes with osteoblast-specific Pdk1 deletion in mice (Pdk1osx mice) and by the genetic interactions observed in mice heterozygous for both osteoblast-specific Pdk1 deletion and either Runx2 or Creb deletion. Finally, treatment of Pdk1osx and Cbp+/- embryos with BMPs in utero partially reversed their skeletal anomalies at birth. These findings illustrate the in vivo function of the PDK1-AKT-CREB/CBP pathway in bone formation and provide proof of principle for in utero growth factor supplementation as a potential therapy for skeletal dysplasias.
Assuntos
Proteína Morfogenética Óssea 2/administração & dosagem , Proteína Morfogenética Óssea 7/administração & dosagem , Proteína de Ligação a CREB/genética , Terapias Fetais/métodos , Proteínas Serina-Treonina Quinases/genética , Síndrome de Rubinstein-Taybi/genética , Síndrome de Rubinstein-Taybi/terapia , Animais , Desenvolvimento Ósseo/genética , Desenvolvimento Ósseo/fisiologia , Proteína Morfogenética Óssea 2/genética , Proteína de Ligação a CREB/deficiência , Subunidade alfa 1 de Fator de Ligação ao Core/deficiência , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/deficiência , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Mutantes , Mutação , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoblastos/patologia , Gravidez , Proteínas Serina-Treonina Quinases/deficiência , Proteínas Serina-Treonina Quinases/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil , Proteínas Recombinantes/administração & dosagem , Síndrome de Rubinstein-Taybi/embriologia , Síndrome de Rubinstein-Taybi/metabolismo , Transdução de Sinais , ÚteroRESUMO
BACKGROUND: The upper respiratory tract functions to protect lower respiratory structures from chemical and biological agents in inspired air. Cellular oxidative stress leading to acute and chronic inflammation contributes to the resultant pathology in many of these exposures and is typical of allergic disease, chronic sinusitis, pollutant exposure, and bacterial and viral infections. Little is known about the effective means by which topical treatment of the nose can strengthen its antioxidant and anti-inflammatory defenses. The present study was undertaken to determine if naturally-occurring plant oils with reported antioxidant activity can provide mechanisms through which upper respiratory protection might occur. METHODS: Controlled exposure of the upper respiratory system to ozone and nasal biopsy were carried out in healthy human subjects to assess mitigation of the ozone-induced inflammatory response and to assess gene expression in the nasal mucosa induced by a mixture of five naturally-occurring antioxidant oils--aloe, coconut, orange, peppermint and vitamin E. Cells of the BEAS-2B and NCI-H23 epithelial cell lines were used to investigate the source and potential intracellular mechanisms of action responsible for oil-induced anti-inflammatory activity. RESULTS: Aerosolized pretreatment with the mixed oil preparation significantly attenuated ozone-induced nasal inflammation. Although most oil components may reduce oxidant stress by undergoing reduction, orange oil was demonstrated to have the ability to induce long-lasting gene expression of several antioxidant enzymes linked to Nrf2, including HO-1, NQO1, GCLm and GCLc, and to mitigate the pro-inflammatory signaling of endotoxin in cell culture systems. Nrf2 activation was demonstrated. Treatment with the aerosolized oil preparation increased baseline levels of nasal mucosal HO-1 expression in 9 of 12 subjects. CONCLUSIONS: These data indicate that selected oil-based antioxidant preparations can effectively reduce inflammation associated with oxidant stress-related challenge to the nasal mucosa. The potential for some oils to activate intracellular antioxidant pathways may provide a powerful mechanism through which effective and persistent cytoprotection against airborne environmental exposures can be provided in the upper respiratory mucosa.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Células Epiteliais/efeitos dos fármacos , Mucosa Nasal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Óleos de Plantas/uso terapêutico , Rinite/tratamento farmacológico , Administração por Inalação , Adulto , Aerossóis , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Biópsia , Linhagem Celular , Estudos Cross-Over , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Cinética , Masculino , Pessoa de Meia-Idade , Fator 2 Relacionado a NF-E2/metabolismo , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Ozônio , Óleos de Plantas/administração & dosagem , RNA Mensageiro/metabolismo , Rinite/induzido quimicamente , Rinite/imunologia , Rinite/metabolismo , Método Simples-Cego , Adulto JovemRESUMO
Effect of iron and chelator on the growth and siderophore production in the ten newly Frankia strains isolated from the root nodules of Hippophae salicifolia D. Don and the two reference strains were studied. Growth of the strains was greatly affected when grown in the iron and EDTA deprived conditions. All the strains were capable of producing both the hydroxamate and catecholate type siderophore that was detected using the Csaky and Arnow assays. Production of siderophore was enhanced in the EDTA replenish condition in contrast to the iron supplemented medium suggesting that EDTA reduces the availability of other free metals and hence creates the stress condition for which the secretion of siderophore is enhanced. A decrease in siderophore production was observed with an increase in iron concentration. Strains HsIi2 and HsIi10 were found to be producing more siderophore than the other strains.
Assuntos
Frankia/efeitos dos fármacos , Ferro/farmacologia , Raízes de Plantas/microbiologia , Rhizobiaceae/metabolismo , Sideróforos/biossíntese , Ácido Edético/farmacologia , Frankia/metabolismo , Hippophae/microbiologia , Quelantes de Ferro/metabolismo , Rhizobiaceae/classificaçãoRESUMO
Oxidative stress has been postulated to play an important role in the pathogenesis of asthma; although a defect in antioxidant responses has been speculated to exacerbate asthma severity, this has been difficult to demonstrate with certainty. Nuclear erythroid 2 p45-related factor 2 (Nrf2) is a redox-sensitive basic leucine zipper transcription factor that is involved in the transcriptional regulation of many antioxidant genes. We show that disruption of the Nrf2 gene leads to severe allergen-driven airway inflammation and hyperresponsiveness in mice. Enhanced asthmatic response as a result of ovalbumin sensitization and challenge in Nrf2-disrupted mice was associated with more pronounced mucus cell hyperplasia and infiltration of eosinophils into the lungs than seen in wild-type littermates. Nrf2 disruption resulted in an increased expression of the T helper type 2 cytokines interleukin (IL)-4 and IL-13 in bronchoalveolar lavage fluid and in splenocytes after allergen challenge. The enhanced severity of the asthmatic response from disruption of the Nrf2 pathway was a result of a lowered antioxidant status of the lungs caused by lower basal expression, as well as marked attenuation, of the transcriptional induction of multiple antioxidant genes. Our studies suggest that the responsiveness of Nrf2-directed antioxidant pathways may act as a major determinant of susceptibility to allergen-mediated asthma.
Assuntos
Asma/etiologia , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Transativadores/deficiência , Transativadores/genética , Acetilcisteína/farmacologia , Animais , Antioxidantes/metabolismo , Asma/metabolismo , Asma/patologia , Sequência de Bases , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Quimiocina CCL11 , Quimiocinas CC/metabolismo , DNA Complementar/genética , Regulação da Expressão Gênica , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Knockout , Fator 2 Relacionado a NF-E2 , NF-kappa B/metabolismo , Ovalbumina/imunologia , Oxirredução , Estresse Oxidativo , Células Th2/imunologiaRESUMO
Description of the root of the plant, Zizyphus mauritiana Linn. the microscopical characters of the powdered root, its behavior on treatment with different chemical reagents, and the fluorescence character under ultraviolet light after treatment were studied to fix some pharmacognostical parameters. Preliminary phytochemical screening on the various extracts of the root of the plant was also performed. These studies were carried out to identify this plant for further research work.