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1.
J Glob Health ; 11: 04038, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484706

RESUMO

Background: By 2030, Sustainable Development Goal 3.4 aims to reduce the premature mortality caused by non-communicable diseases through prevention and treatment. Chronic obstructive pulmonary disease is the second leading cause of mortality and disability-adjusted life years in India. This review was conducted to estimate the prevalence of COPD using systematic review and meta-analysis technique. Method: Search was conducted using six databases for studies on COPD among population above 30 years in India between years 2000 to 2020. Cross-sectional and cohort studies reporting prevalence of COPD and associated risk factors were included in the present review. Screening and data extraction was done by two authors independently. Studies were appraised for quality using the modified New Castle Ottawa scale and reporting quality was assessed using STROBE guidelines. Result: Our search returned 8973 records, from which 23 records fulfilled the eligibility criteria. Overall, the prevalence of COPD among population aged 30 years and above in India was 7%. Risk factors like active and passive smoking, biomass fuel exposure, environmental tobacco smoke, occupational exposure to dust, indoor and outdoor pollution, and increasing age were reported to have a significant association with COPD among Indian population. Conclusion: Our findings suggest the need for a multicentric national-level research study to understand COPD burden and its contributing risk factors. The findings also suggest the need for COPD sensitive health literacy program focused on early screening and primary prevention of risk factors for COPD, which may help early initiation of self-management practices, that are crucial for better quality of life.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Estudos Transversais , Humanos , Índia/epidemiologia , Prevalência , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fatores de Risco
2.
Artigo em Inglês | MEDLINE | ID: mdl-34383913

RESUMO

OBJECTIVES: FtsZ is an essential bacterial protein and an unexplored target for the development of antibacterial drugs. The development of a novel inhibitor targeting FtsZ offers a potential opportunity to combat drug resistance. DS01750413, a new derivative of PC190723, is a novel FtsZ inhibitor with improved in vitro and in vivo activity. The objective of this study was to investigate the efficacy of DS01750413 against Staphylococcus spp., including MRSA, in in vitro and in vivo models. METHODS: In vitro activities of DS01750413 and standard-of-care antibiotics were evaluated against clinical isolates of Gram-positive pathogens. The in vivo efficacy was evaluated in a murine systemic infection model caused by MRSA. RESULTS: DS01750413 showed potent in vitro activity against MRSA clinical isolates with MIC ranges of 0.5-1 mg/L and also demonstrated concentration-dependent bactericidal killing. In the murine bacteraemia infection model of MRSA, treatment with DS01750413 resulted in prolonged survival of animals compared with placebo-treated animals and exhibited a significant reduction in the bacterial load in liver, spleen, lungs and kidneys. CONCLUSIONS: DS01750413 showed encouraging in vitro and in vivo activity against MRSA. As a novel chemical class, DS01750413 has the potential to become clinically viable antibiotics to address the drug resistance problem by its unique novel targeting mechanism of action.

3.
Future Microbiol ; 16: 871-877, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34318681

RESUMO

Aim: To investigate the antileishmanial activity of novel azole compounds against Leishmania donovani, which causes deadly visceral leishmaniasis disease. Materials & methods: A focused azole-based library was screened against both promastigotes and amastigotes forms of L. donovani strains in flat-bottomed 96-well tissue culture plates and J774A.1 macrophage cell-line infected with L. donovani. The comprehensive screening of azole-based library against L. donovani strains provided novel hits, which can serve as a good starting point to initiate hit to lead optimization campaign. Results: Hits identified from azole-based library exhibited potent in vitro activity against promastigotes and amastigotes of L. donovani. Conclusion: These potent novel azole hits could be a good starting point to carry out for further medicinal chemistry exploration for antileishmania program.

4.
Extremophiles ; 25(3): 203-219, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33768388

RESUMO

Technological advances in the field of life sciences have led to discovery of organisms that live in harsh environmental conditions referred to as extremophiles. These organisms have adapted themselves to thrive in extreme habitat giving these organisms an advantage over conventional mesophilic organisms in various industrial applications. Extremozymes produced by these extremophiles have high tolerance to inhospitable environmental conditions making them an ideal enzyme system for various industrial processes. A notable application of these extremophiles and extremozymes is their use in the degradation of recalcitrant lignocellulosic biomass and application in biorefineries. For maximum utilization of the trapped carbon source from this obstinate biomass, pretreatment is a necessary step that requires various physiochemical and enzymatic treatments. From search for novel extremophiles and extremozymes to development of various genetic and protein engineering techniques, investigation on extremozymes with enhanced stability and efficiency is been done. Since extremozymes are easily calibrated to work under such conditions, they have become an emerging topic in the research field of biofuel production. The review discusses the various extremozymes that play an important role in lignocellulose degradation along with recent studies on their molecular and genetic evolution for industrial application and production of biofuels and various value-added products.


Assuntos
Extremófilos , Biocombustíveis , Biomassa , Lignina
5.
Clin Epidemiol Glob Health ; 9: 110-115, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32838065

RESUMO

Background: Coronavirus disease 2019 (COVID-19) has spread throughout the world and become a global pandemic. This has hampered and led to drastic changes in the functioning of healthcare services, forcing the professionals to adapt and work efficiently. The present study aimed to explore the impact of COVID-19 on the professional practices of audiologists and speech-language pathologists in India using a cross-sectional knowledge, attitude and practices survey. Material and methods: The study was conducted in two phases; phase one involved development and validation of the questionnaire, while phase II involved data collection. A cross-sectional self-reported internet-based study using convenience sampling was carried out. Results: Two hundred and eleven audiologists and speech-language pathologists responded to the survey. Overall, the professionals exhibited good knowledge levels regarding the COVID-19 outbreak. However, there were differences in their attitudes towards service delivery in the midst of the pandemic. Further, poor practices towards infection control measures especially in terms of hand washing was noted. Conclusion: The findings of the present study are useful in highlighting the need to create better awareness among these professionals about appropriate and standard infection control measures. There is a need to have in place standard operating protocols for hand wash and infection control as well as inclusion in curriculum.

6.
Biotechnol Rep (Amst) ; 28: e00525, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32963975

RESUMO

For sustainable growth, concept of biorefineries as recourse to the "fossil derived" energy source is important. Here, the Carbohydrate Active enZymes (CAZymes) play decisive role in generation of biofuels and related sugar-based products utilizing lignocellulose as a carbon source. Given their industrial significance, extensive studies on the evolution of CAZymes have been carried out. Various bacterial and fungal organisms have been scrutinized for the development of CAZymes, where advance techniques for strain enhancement such as CRISPR and analysis of specific expression systems have been deployed. Specific Omic-based techniques along with protein engineering have been adopted to unearth novel CAZymes and improve applicability of existing enzymes. In-Silico computational research and functional annotation of new CAZymes to synergy experiments are being carried out to devise cocktails of enzymes for use in biorefineries. Thus, with the establishment of these technologies, increased diversity of CAZymes with broad span of functions and applications is seen.

7.
Nanotechnology ; 30(38): 385502, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31181546

RESUMO

Metal nanostructures with highly branched morphologies are attractive due to their fascinating plasmonic properties which are related to their unique morphological features. In this work a simple fabrication methodology is used for fabrication of surface-enhanced Raman spectroscopy (SERS) substrates composed of branched silver nanostructures with dendritic morphology. The high Raman intensity enhancement factor of the order ∼1010 was achieved which allows the detection of ∼zeptomole thiram molecules by SERS substrates. The appearance of new bands at 344 cm-1 and 1521 cm-1 provides an evidence of contribution of chemical enhancement in SERS. The observed spectral changes in SERS spectrum originate from the adsorption of the analyte on the metal surface and provide an insight into molecule-metal interaction in SERS. The extreme sensitivity of SERS substrates is discussed in terms of the distinction between electromagnetic and chemical enhancement mechanisms. Moreover, the highly sensitive SERS substrates were used for simultaneous detection of Rhodamine B and thiram molecules from their mixture with different individual concentrations demonstrating detection capabilities for the identification of pesticides with dye molecules.

8.
Sci Rep ; 9(1): 441, 2019 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-30679759

RESUMO

Plant populations growing along an altitudinal gradient are exposed to different environmental conditions. They are excellent resources to study regulatory mechanisms adopted by plants to respond to different environmental stresses. Regulation by miRNA is one of such strategies. Here, we report how different miRNAs are preferentially expressed in the three natural populations of A. thaliana originating from a wide altitudinal range. The expression level of miRNAs was mostly governed by temperature and radiation. Majority of the identified miRNAs expressed commonly in the three populations. However, 30 miRNAs expressed significantly at different level between the low and the high altitude populations. Most of these miRNAs regulate the genes associated with different developmental processes, abiotic stresses including UV, cold, secondary metabolites, etc. Further, the expression of miR397 and miR858 involved in lignin biosynthesis and regulation of secondary metabolites respectively, may be regulated by light intensity. A few miRNAs expressed at increasing level with the increase in the altitude of the site indicating environment driven tight regulation of these miRNAs. Further, several novel miRNAs and isomiR diversity specific to the Himalayas are reported which might have an adaptive advantage. To the best of our knowledge, this is the first report on miRNA expression from natural plant populations.


Assuntos
Altitude , Arabidopsis/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas/genética , MicroRNAs/genética , Estresse Fisiológico/genética , Adaptação Fisiológica/genética , Adaptação Fisiológica/efeitos da radiação , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Lignina/biossíntese , Modelos Genéticos , Estresse Fisiológico/efeitos da radiação , Temperatura , Raios Ultravioleta
9.
Bioorg Med Chem Lett ; 27(15): 3454-3459, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28587823

RESUMO

A non-diaryl quinoline scaffold 6,7-dihydropyrazolo[1,5-a]pyrazin-4-one was identified by screening of diverse set of compounds against M. smegmatis ATP synthase. Herein, we disclose our efforts to develop the structure activity relationship against Mycobacterium tuberculosis (Mtb.H37Rv strain) around the identified hit 1. A scaffold hopping approach was used to identify compounds 14a, 14b and 24a with improved activity against MTb.H37Rv.


Assuntos
Complexos de ATP Sintetase/antagonistas & inibidores , Antituberculosos/química , Antituberculosos/farmacologia , Mycobacterium tuberculosis/enzimologia , Quinolinas/química , Quinolinas/farmacologia , Complexos de ATP Sintetase/metabolismo , Antituberculosos/síntese química , Desenho de Fármacos , Humanos , Mycobacterium tuberculosis/efeitos dos fármacos , Pirazinas/síntese química , Pirazinas/química , Pirazinas/farmacologia , Quinolinas/síntese química , Relação Estrutura-Atividade , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia
10.
Biomed Pharmacother ; 83: 942-957, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27522257

RESUMO

OBJECTIVE: This study aims to evaluate the skeletal effects of dalbergin (DBN), isolated from Dalbergia sissoo heartwood, in ovariectomized (OVx) BALB/c mice, a postmenopausal osteoporosis model of bone loss. METHODS: Adult BALB/c mice were used and randomly assigned in to six groups with 6 animals (n=6) in each group: sham (surgery operated without ovariectomy) with vehicle, ovariectomy with vehicle, ovariectomy (OVx) with estradiol (E2 5.0µgkg-1day-1), or ovariectomy with dalbergin at three different doses of DBN (1.0, 5.0 and10mgkg-1day-1). Daily oral administration of the vehicle, estradiol, or DBN was started 8 weeks post-surgery and continued for 8 weeks. At the end of experiment, mice were sacrificed and assessed for trabecular bone structure of tibia, lumbar vertebra (L5) and alterations in biochemical and uterine parameters, pharmacokinetic profile and gene expression were monitored for each group. RESULTS: Treatment with DBN prevented trabecular bone loss in cancellous bone in the tibial metaphysis and lumbar vertebra region of the ovariectomized mice. Micro-CT data showed that mice treated with DBN at 1.0mgkg-1day-1 exhibited improved bone micro-architecture that was sustained with decreased expression of bone resorption markers like TRAP and RANK and caused an increase in osteogenic markers like RUNX2, BMP2 and OPG/RANKL ratio compared with OVx+vehicle treated mice. Moreover, DBN treatment induced no uterine estrogenicity and significantly lowered the osteocalcin amount in serum when compared with OVx+V group. DBN reached its maximum concentration (Cmax) 238.49±21.37ngml-1 in serum as early as 1h of administration. Overall, DBN (1.0mgkg-1day-1) treatment exhibited similar bone conserving effect against bone-loss as estradiol treatment. CONCLUSION: Daily oral administration of DBN for 8 weeks showed significant anabolic effects on bone micro-architectural parameters along with down regulation of bone resorptive markers without compromising safety at uterine level. Therefore, our study provides basis for DBN as a therapeutic candidate against postmenopausal osteoporosis.


Assuntos
Cumarínicos/uso terapêutico , Dalbergia/química , Fêmur/patologia , Flavonoides/uso terapêutico , Osteoporose/tratamento farmacológico , Ovariectomia , Substâncias Protetoras/uso terapêutico , Administração Oral , Fosfatase Alcalina/metabolismo , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Fenômenos Biomecânicos/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Remodelação Óssea/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Osso Esponjoso/efeitos dos fármacos , Osso Esponjoso/patologia , Cumarínicos/administração & dosagem , Cumarínicos/química , Cumarínicos/farmacocinética , Modelos Animais de Doenças , Feminino , Fêmur/efeitos dos fármacos , Fêmur/fisiopatologia , Flavonoides/administração & dosagem , Flavonoides/química , Flavonoides/farmacocinética , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Camundongos Endogâmicos BALB C , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteocalcina/sangue , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteoporose/diagnóstico por imagem , Osteoporose/genética , Osteoporose/patologia , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/química , Substâncias Protetoras/farmacocinética , Útero/efeitos dos fármacos , Útero/patologia , Microtomografia por Raio-X
11.
Int Immunopharmacol ; 10(4): 467-73, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20093202

RESUMO

The p38 mitogen activated protein kinase (MAPK) is a key signaling molecule that plays a crucial role in the progression of various inflammatory diseases such as rheumatoid arthritis (RA), asthma and chronic obstructive pulmonary disease. The objective of the present study was to evaluate the anti-inflammatory activity of a p38 MAPK inhibitor, AW-814141. AW-814141 inhibited enzymatic activity of recombinant p38-alpha and beta isoforms with IC(50) value of 100nM and 158nM, respectively. AW-814141 also inhibited the release of tumor necrosis factor (TNF)-alpha by lipopolysaccharide (LPS) treated human peripheral blood mononuclear cells with an IC(50) value of 212nM and demonstrated selectivity against a panel of few kinases. Oral administration of AW-814141 (10mpk) in LPS-injected mice resulted in a significant reduction in TNF-alpha production in the circulation. In a carrageenan-induced rat paw edema model and collagen-induced arthritis model (CIA), AW-814141 dose dependently inhibited paw swelling. In different in vivo efficacy models, efficacy of AW-814141 was found to be better as compared to the reference compounds (Vx-745 and BIRB-796). This study demonstrated that AW-814141 is a novel p38 MAPK inhibitor and it displays promising in vitro and in vivo anti-inflammatory activities and can be used for the treatment of rheumatoid arthritis.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Piridonas/farmacologia , Pirimidinas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Carragenina , Morte Celular/efeitos dos fármacos , Colágeno , Citocinas/metabolismo , Edema/induzido quimicamente , Edema/prevenção & controle , Ativação Enzimática/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Cinética , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , NF-kappa B/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacocinética , Piridonas/farmacocinética , Pirimidinas/farmacocinética , Ratos , Ratos Wistar , Especificidade por Substrato , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/farmacocinética
12.
Bioorg Med Chem ; 16(3): 1162-73, 2008 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-18024138

RESUMO

A series of 2- and 3-OH Nile red dyes was prepared in order to generate water-soluble probes that could be used to probe lipid binding to proteins. Various substitutions in positions 2-/3-, 6-, and 7-shifted wavelengths while maintaining the environmental sensitivity of Nile red. In order to increase the solubility of the dyes in aqueous solutions, we attached butyric acid groups to the 2- or 3-OH position. In addition, phenothiazine dyes, which exhibited particularly long excitation properties, were synthesized and tested for the first time. All dyes showed Stoke's shifts of 70-100 nm and changes in excitation and emission of over 100 nm, depending on the hydrophobicity of the environment. Binding studies with bovine serum albumin and the non-specific lipid transfer protein SCP2 revealed emission changes of more than 30 nm upon binding to the protein and a five-fold increase in emission intensity. Titration of the dye-loaded proteins with various lipids or drugs replaced the dye and thereby reversed the shift in wavelength intensity. This allowed us to estimate the lipid binding affinity of the investigated proteins. For SCP2, isothermal calorimetry (ITC) data verified the titration experiments. NMR titration experiments of SCP2 with Nile red 2-O-butyric acid (1a) revealed that the dye is bound within the lipid binding pocket and competes with lipid ligands for this binding site. These results give valuable insight into lipid and drug transport by proteins outside and inside cells.


Assuntos
Corantes Fluorescentes/química , Lipídeos/química , Preparações Farmacêuticas/química , Alquilação , Animais , Ácido Butírico/química , Calorimetria , Proteínas de Transporte/química , Bovinos , Corantes Fluorescentes/síntese química , Humanos , Modelos Moleculares , Estrutura Molecular , Soroalbumina Bovina/química , Titulometria
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