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1.
Front Cell Infect Microbiol ; 14: 1375872, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38846355

RESUMEN

Introduction: Pseudomonas aeruginosa is notorious for its multidrug resistance and its involvement in hospital-acquired infections. In this study, 20 bacterial strains isolated from soil samples near the Hindan River in Ghaziabad, India, were investigated for their biochemical and morphological characteristics, with a focus on identifying strains with exceptional drug resistance and pyocyanin production. Methods: The isolated bacterial strains were subjected to biochemical and morphological analyses to characterize their properties, with a particular emphasis on exopolysaccharide production. Strain GZB16/CEES1, exhibiting remarkable drug resistance and pyocyanin production. Biochemical and molecular analyses, including sequencing of its 16S rRNA gene (accession number LN735036.1), plasmid-curing assays, and estimation of plasmid size, were conducted to elucidate its drug resistance mechanisms and further pyocynin based target the Candida albicans Strain GZB16/CEES1 demonstrated 100% resistance to various antibiotics used in the investigation, with plasmid-curing assays, suggesting plasmid-based resistance gene transmission. The plasmid in GZB16/CEES1 was estimated to be approximately 24 kb in size. The study focused on P. aeruginosa's pyocyanin production, revealing its association with anticandidal activity. The minimum inhibitory concentration (MIC) of the bacterial extract against Candida albicans was 50 µg/ml, with a slightly lower pyocyanin-based MIC of 38.5 µg/ml. Scanning electron microscopy illustrated direct interactions between P. aeruginosa strains and Candida albicans cells, leading to the destruction of the latter. Discussion: These findings underscore the potential of P. aeruginosa in understanding microbial interactions and developing strategies to combat fungal infections. The study highlights the importance of investigating bacterial-fungal interactions and the role of pyocyanin in antimicrobial activity. Further research in this area could lead to the development of novel therapeutic approaches for combating multidrug-resistant infections.


Asunto(s)
Antifúngicos , Candida albicans , Farmacorresistencia Bacteriana Múltiple , Pruebas de Sensibilidad Microbiana , Plásmidos , Pseudomonas aeruginosa , Piocianina , ARN Ribosómico 16S , Microbiología del Suelo , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Piocianina/metabolismo , Farmacorresistencia Bacteriana Múltiple/genética , Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Candida albicans/genética , Candida albicans/crecimiento & desarrollo , ARN Ribosómico 16S/genética , India , Plásmidos/genética , Antibacterianos/farmacología , Antibiosis
2.
Brain Res ; 1834: 148886, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38582413

RESUMEN

Alzheimer's disease (AD) has few effective treatment options and continues to be a major global health concern. AD is a neurodegenerative disease that typically affects elderly people. Alkaloids have potential sources for novel drug discovery due to their diverse chemical structures and pharmacological activities. Alkaloids, natural products with heterocyclic nitrogen-containing structures, are considered potential treatments for AD. This review explores the neuroprotective properties of alkaloids in AD, focusing on their ability to regulate pathways such as amyloid-beta aggregation, oxidative stress, synaptic dysfunction, tau hyperphosphorylation, and neuroinflammation. The FDA has approved alkaloids such as acetylcholinesterase inhibitors like galantamine and rivastigmine. This article explores AD's origins, current market medications, and clinical applications of alkaloids in AD therapy. This review explores the development of alkaloid-based drugs for AD, focusing on pharmacokinetics, blood-brain barrier penetration, and potential adverse effects. Future research should focus on the clinical evaluation of promising alkaloids, developing recently discovered alkaloids, and the ongoing search for novel alkaloids for medical treatment. A pharmaceutical option containing an alkaloid may potentially slow down the progression of AD while enhancing its symptoms. This review highlights the potential of alkaloids as valuable drug leads in treating AD, providing a comprehensive understanding of their mechanisms of action and therapeutic implications.


Asunto(s)
Alcaloides , Enfermedad de Alzheimer , Fármacos Neuroprotectores , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Alcaloides/farmacología , Alcaloides/uso terapéutico , Animales , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Péptidos beta-Amiloides/metabolismo , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/uso terapéutico , Estrés Oxidativo/efectos de los fármacos
3.
Prep Biochem Biotechnol ; 53(9): 1143-1153, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36840506

RESUMEN

Sponges forms association with many bacteria that serve as sources of new bioactive compounds. The compounds are produced in response to environmental and nutritional conditions of the environment that enable them to protect their host from colonization. In this study, three sponge bacterial endophytes were isolated, identified, and subjected to solvent extraction processes. The identified bacteria are Bacillus amyloquifaciens, Bacillus paramycoides, and Enterobacter sp. The bacteria were cultured in two different fermentation media with varying nutritional composition for the extraction process. The extracts were evaluated for antibacterial and antibiofilm activity against microfouling bacteria and the chemical composition of each extract was analyzed via gas chromatography-mass spectrometry (GC-MS). The extract from the endophytes shows varying antibacterial and antibiofilm activity against the tested strains. Several compounds were detected from the extracts including some with known antibacterial/antibiofilm activity. The results showed variations in activity and secondary metabolite production between the extracts obtained under different nutritional composition of the media. In conclusion, this study indicated the role of nutrient composition in the activity and secondary metabolites production by bacteria associated with sponge Also, this study confirmed the role of sponge bacterial endophytes as producers of bioactive compounds with potential application as antifouling (AF) agents.


Asunto(s)
Antibacterianos , Endófitos , Endófitos/metabolismo , Antibacterianos/química , Enterobacter/metabolismo , Extractos Vegetales/química , Biopelículas , Pruebas de Sensibilidad Microbiana
4.
Nanomaterials (Basel) ; 12(24)2022 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-36558216

RESUMEN

The potential for trophic transfer of single-walled carbon nanotubes (SWCNTs) was assessed using the green algae Tetraselmis suecica and the blue mussel Mytilus edulis in a series of laboratory experiments. Swanee River Natural Organic Matter (SRNOM)-dispersed SWCNTs were introduced into growing algal cultures. Light microscopical observations, confirmed by scanning electronic microscopy (SEM) and Raman spectroscopy, showed that SWCNT agglomerates adhered to the external algal cell walls and transmission electronic microscopy (TEM) results suggested internalization. A direct effect of SWCNT exposure on the algae was a significant decrease in growth, expressed as chlorophyll a concentration and cell viability. Mussels, fed with algae in the presence of SWCNTs, led to significantly increased pseudofaeces production, indicating selective feeding. Nevertheless, histological sections of the mussel digestive gland following exposure showed evidence of SWCNT-containing algae. Furthermore, DNA damage and oxidative stress biomarker responses in the mussel haemocytes and gill tissue were significantly altered from baseline values and were consistent with previously observed responses to SWCNT exposure. In conclusion, the observed SWCNT-algal interaction demonstrated the potential for SWCNT entrance at the base of the food chain, which may facilitate their trophic transfer with potential consequences for human exposure and health.

5.
Plants (Basel) ; 11(19)2022 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-36235468

RESUMEN

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a common disease among elderly men. Its pharmacological treatment is still unsatisfactory. 6-Paradol (6-PD) is an active metabolite found in many members of the Zingiberaceae family. It was reported to possess anti-proliferative, antioxidant, and anti-inflammatory activities. The present study aimed at exploring the potential of 6-PD to inhibit testosterone-induced BPH in rats as well as the probable underlying mechanism. METHODS: Male Wistar rats were divided into 6 groups and treated as follows: Group 1 (control group) received vehicles only, Group 2 testosterone only, Groups 3 and 4 received 6-PD (2.5 and 5.0 mg/kg; respectively) and testosterone, and Group 6 received finasteride and testosterone. RESULTS: Daily treatment of animals with 6-PD at the two dose levels of 2.5 and 5 mg/kg significantly ameliorated a testosterone-induced rise in prostate index and weight. This was confirmed by histological examinations of prostatic tissues that indicated a reduction in the pathological changes as well as inhibition of the rise in glandular epithelial height in 6-PD treated rats. Immunohistochemical investigations showed that 6-PD prevented the up-regulation of cyclin D1 induced by testosterone injections. Further, 6-PD significantly modulated mRNA expression of both Bcl2 and Bax in prostate tissues of testosterone-treated rats in favor of anti-proliferation. It also showed antioxidant activities as evidenced by inhibition of accumulation of malondialdehyde (MDA) and exhaustion of catalase (CAT) activity. In addition, 6-PD displayed significant anti-inflammatory activities as it prevented up-regulation of interleukin-6 (IL-6) and nuclear factor kappa B (NF-κB). Immunoblotting analysis revealed that 6-PD significantly inhibited testosterone-induced activation of AKT and mTOR in prostate tissues. CONCLUSIONS: 6-PD protects against testosterone-induced BPH in rats. This can be attributed, at least partly, to its antiproliferative, antioxidant, and anti-inflammatory properties as well as its ability to inhibit activation of the AKT/mTOR axis.

6.
Molecules ; 27(14)2022 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-35889532

RESUMEN

A brain tumor (BT) is a condition in which there is growth or uncontrolled development of the brain cells, which usually goes unrecognized or is diagnosed at the later stages. Since the mechanism behind BT is not clear, and the various physiological conditions are difficult to diagnose, the success rate of BT is not very high. This is the central issue faced during drug development and clinical trials with almost all types of neurodegenerative disorders. In the first part of this review, we focus on the concept of brain tumors, their barriers, and the types of delivery possible to target the brain cells. Although various treatment methods are available, they all have side effects or toxic effects. Hence, in the second part, a correlation was made between the use of resveratrol, a potent antioxidant, and its advantages for brain diseases. The relationship between brain disease and the blood-brain barrier, multi-drug resistance, and the use of nanomedicine for treating brain disorders is also mentioned. In short, a hypothetical concept is given with a background investigation into the use of combination therapy with resveratrol as an active ingredient, the possible drug delivery, and its formulation-based approach.


Asunto(s)
Neoplasias Encefálicas , Estilbenos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Encéfalo , Neoplasias Encefálicas/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Humanos , Preparaciones Farmacéuticas , Resveratrol/uso terapéutico , Estilbenos/farmacología , Estilbenos/uso terapéutico
7.
Environ Sci Pollut Res Int ; 29(34): 52220-52232, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35260981

RESUMEN

The present study's aims of isolation, characterization and in vitro antioxidant activity screening of pure compound from Black pepper (Piper nigrum) were investigated. Nowadays, scientific exploration of medicinal plants from natural sources has become the prime concern globally. All the crude drugs that have been isolated from natural plant origin (herbs, root, stem, bark, fruit and flower) have great significance in drug discovery as well as a lead compound to demonstrate great synergistic effect on pharmacology. For this research work, methanol was selected as a mother solvent, and the crude methanolic extract of black pepper was partitioned in between the solvent chloroform and di-ethyl-ether. A crystal fraction has been eradicated from the chloroform extract of black pepper (Piper nigrum). The crystal compound (C1) was isolated and purified by using thin layer chromatography (TLC) and recrystallization technique. The purified crystal compound (C1) isolated from black pepper possesses a strong in vitro antioxidant activity. The IC50 value of crystal compound (C1) was 4.1 µg/ml where the standard one had 3.2 µg/ml. Physical, phytochemical and chromatographical characterization of pure crystal compound (C1) has been explored, and from the analysis of all characteristics, it was found that, crystal compound (C1) might have resembling features of the standard Piperine of black pepper. The overall research work was really remarkable and introduced a convenient way of isolating pure compound from the natural source which will be a great referential resource in isolating crude drugs for future analysis.


Asunto(s)
Piper nigrum , Antioxidantes/farmacología , Cloroformo , Extractos Vegetales/farmacología , Solventes
8.
Braz. arch. biol. technol ; 64: e21180747, 2021. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1345490

RESUMEN

Abstract Owing to the excellent catalytic potential, β-galactosidase (EC: 3.2.1.23) has been exploited as an important industrial enzyme for obtaining galactooligosaccharides (GOS) and lactose-free products in dairy industries. Moreover, novel technologies have been implemented in the recent past for preparing and modifying nanoparticles (NPs) for immobilizing therapeutically and industrially important enzymes. Nanoparticles based enzyme immobilization (NBEI) offered more stability and robustness to the enzymes due to their fixed conformation and hence extend their applications in broader areas. A quick overview of the results exhibited greater activity for the enzymes immobilized on NPs as compared to enzyme immobilized on 2-D matrices. Based on these findings, this review was aimed to emphasize the recent development achieved for immobilizing β-galactosidase on NPs with their specific utilization in obtaining dairy products. These studies includes β-galactosidases from various sources that were immobilized on various NPs for hydrolyzing lactose in batch and continuous reactors, and for the production of GOS in biotechnology industries. NBEI of β-galactosidase offered profound stability for transporting substrate and product for enzymatic reactions, apart from cost effective advantage due to reusable nature of immobilized enzyme.


Asunto(s)
beta-Galactosidasa , Industria Lechera , Enzimas , Nanopartículas
9.
Mater Sci Eng C Mater Biol Appl ; 111: 110829, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32279826

RESUMEN

This study concentrates on biosynthesis of Silver Nanoparticles (AgNPs) from stem extract of Acacia nilotica (A. nilotica). The reaction was completed at a temperature ~40-45 °C and time duration of 5 h. AgNPs were thoroughly investigated via advanced characterization techniques such as UV-Vis spectrophotometry (UV-Vis), Fourier Transform Infrared spectroscopy (FTIR), X-ray Diffractometry (XRD), Field Emission Scanning Electron Microscopy (FESEM), High Resolution Transmission Electron Microscopy (HRTEM), X-ray Photoelectron Spectroscopy (XPS), Thermo Gravimetric Analysis (TGA), Diffuse Reflectance Spectroscopy (DRS), Brunner-Emmett-Teller (BET), Dynamic Light Scattering (DLS), and Zeta potential analysis. AgNPs with average size below 50 nm were revealed by all the measuring techniques. Maximum surface area ~5.69 m2/g was reported for the as synthesized NPs with total pore volume ~0.0191 mL/g and average pore size ~1.13 nm. Physical properties such as size and shape have changed the surface plasmon resonance peak in UV-visible spectrum. Antimicrobial activity was reported due to denaturation of microbial ribosome's sulphur and phosphorus bond by silver ions against bacterium Methicillin Resistant Staphylococcus aureus (MRSA) and fungus Candida Albican (CA). Furthermore, AgNPs degraded toxic pollutants such as 4-nitrophenol (4-NP), 2-nitrophenol (2-NP) and various hazardous dyes such as Congo Red (CR), Methylene Blue (MB) and Methyl Orange (MO) up to 95%. The present work provided low cost, green and an effective way for synthesis of AgNPs which were utilized as potential antimicrobial agents as well as effective catalyst for detoxification of various pollutants and dyes.


Asunto(s)
Acacia/metabolismo , Antiinfecciosos/farmacología , Contaminantes Ambientales/toxicidad , Nanopartículas del Metal/química , Compuestos Orgánicos/toxicidad , Metabolismo Secundario , Plata/farmacología , Candida albicans/efectos de los fármacos , Catálisis , Colorantes/química , Dispersión Dinámica de Luz , Cinética , Nanopartículas del Metal/ultraestructura , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Nitrógeno/química , Nitrofenoles/química , Espectroscopía de Fotoelectrones , Extractos Vegetales/farmacología , Metabolismo Secundario/efectos de los fármacos , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Electricidad Estática , Temperatura , Termogravimetría , Difracción de Rayos X
10.
Front Genet ; 10: 1163, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31824568

RESUMEN

Rheumatoid arthritis (RA) is a chronic synovial autoinflammatory disease that destructs the cartilage and bone, leading to disability. The functional regulation of major immunity-related pathways like nuclear factor kappa B (NF-κB), which is involved in the chronic inflammatory reactions underlying the development of RA, remains to be explored. Therefore, this study has adopted statistical and knowledge-based systemic investigations (like gene correlation, semantic similarity, and topological parameters based on graph theory) to study the gene expression status of NF-κB protein family (NKPF) and its regulators in synovial tissues to trace the molecular pathways through which these regulators contribute to RA. A complex protein-protein interaction map (PPIM) of 2,742 genes and 37,032 interactions was constructed from differentially expressed genes (p ≤ 0.05). PPIM was further decomposed into a Regulator Allied Protein Interaction Network (RAPIN) based on the interaction between genes (5 NKPF, 31 seeds, 131 hubs, and 652 bottlenecks). Pathway network analysis has shown the RA-specific disturbances in the functional connectivity between seed genes (RIPK1, ATG7, TLR4, TNFRSF1A, KPNA1, CFLAR, SNW1, FOSB, PARVA, CX3CL1, and TRPC6) and NKPF members (RELA, RELB, NFKB2, and REL). Interestingly, these genes are known for their involvement in inflammation and immune system (signaling by interleukins, cytokine signaling in immune system, NOD-like receptor signaling, MAPK signaling, Toll-like receptor signaling, and TNF signaling) pathways connected to RA. This study, for the first time, reports that SNW1, along with other NK regulatory genes, plays an important role in RA pathogenesis and might act as potential biomarker for RA. Additionally, these genes might play important roles in RA pathogenesis, as well as facilitate the development of effective targeted therapies. Our integrative data analysis and network-based methods could accelerate the identification of novel drug targets for RA from high-throughput genomic data.

11.
Sci Rep ; 9(1): 13678, 2019 09 23.
Artículo en Inglés | MEDLINE | ID: mdl-31548590

RESUMEN

Eucalyptus globulus is an aromatic medicinal plant which known for its 1,8-cineole main pharmacological constituent exhibits as natural analgesic agent. Eucalyptus globulus-loaded micellar nanoparticle was developed via spontaneous emulsification technique and further evaluation for its analgesic efficacy study, in vivo analgesic activity assay in rats. The nanoemulsion system containing Eucalyptus-micelles was optimized at different surfactant types (Tween 40, 60 and 80) and concentrations (3.0, 6.0, 9.0, 12.0, 15.0, and 18.0 wt. %). These formulations were characterized by thermodynamically stability, viscosity, micelles particle size, pH, and morphology structure. The spontaneous emulsification technique offered a greener micelles formation in nanoemulsion system by slowly titrated of organic phase, containing Eucalyptus globulus (active compound), grape seed oil (carrier oil) and hydrophilic surfactant into aqueous phase, and continuously stirred for 30 min to form a homogeneity solution. The characterizations evaluation revealed an optimized formulation with Tween 40 surfactant type at 9.0 wt. % of surfactant concentration promoted the most thermodynamic stability, smaller micelles particle size (d = 17.13 ± 0.035 nm) formed with spherical shape morphological structure, and suitable in viscosity (≈2.3 cP) and pH value (6.57) for transdermal purpose. The in vivo analgesic activity assay of optimized emulsion showed that the transdermal administration of micellar nanoparticle of Eucalyptus globulus on fore and hind limb of rats, possessed the central and peripheral analgesic effects by prolonged the rats pain responses towards the heat stimulus after being put on top of hot plate (55 °C), with longest time responses, 40.75 s at 60 min after treatment administration. Thus, this study demonstrated that micellar nanoparticle of Eucalyptus globulus formed in nanoemulsion system could be promising as an efficient transdermal nanocarrier for the analgesic therapy alternative.


Asunto(s)
Emulsiones/farmacología , Aceite de Eucalipto/farmacología , Umbral del Dolor/efectos de los fármacos , Dolor/tratamiento farmacológico , Animales , Emulsiones/química , Emulsiones/uso terapéutico , Aceite de Eucalipto/química , Aceite de Eucalipto/uso terapéutico , Calor , Masculino , Micelas , Nanotecnología , Ratas , Ratas Sprague-Dawley
12.
J Microbiol Methods ; 166: 105716, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31499093

RESUMEN

We provide a novel one-step/one-pot bio-inspired method of synthesis for Myristica fragrans leaf ester (MFLE) capped­zinc oxide nanoparticles (MFLE-ZnONPs). Antibacterial and antbiofilm efficacies of MFLE-ZnONPs were tested against the multi-drug resistant (MDR) Escherichia coli (E. coli-336), methicillin-resistant Staphylococcus aureus (MRSA-1) and methicillin-sensitive (MSSA-2) clinical isolates. Antibacterial screening using well diffusion assay revealed the cytotoxicity of MFLE-ZnONPs in the range of 500-2000 µg/ml. MFLE-ZnONPs significantly increased the zone of growth inhibition of E. coli-336 (17.0 ±â€¯0.5 to 19.25 ±â€¯1.0 mm), MSSA-2 (16.75 ±â€¯0.8 to 19.0 ±â€¯0.7 mm) and MRSA-1 (16.25 ±â€¯1.0 to 18.25 ±â€¯0.5 mm), respectively. The minimum inhibitory concentration (MIC) and minimum bactericidal concentrations (MBC) against E. coli-336, MRSA-1 and MSSA-2 were found to be 1500, 1000 and 500 µg/ml, and 2500, 2000 and 1500 µg/ml, respectively. A time and dose dependent reduction in the cell proliferation were also found at the respective MICs of tested strains. Scanning electron microscopy (SEM) of MFLE-ZnONPs-treated strains exhibited cellular damage via loss of native rod and coccoid shapes because of the formation of pits and cavities. E. coli-336 and MRSA-1 strains at their MICs (1500 and 1000 µg/ml) sharply reduced the biofilm production to 51% and 24%. The physico-chemical characterization via x-ray diffraction (XRD) ascertained the crystallinity and an average size of MFLE-ZnONPs as 48.32 ±â€¯2.5 nm. Gas chromatography-mass spectroscopy (GC-MS) analysis of MFLE-ZnONPs unravelled the involvement of two bio-active esters (1) butyl 3-oxobut-2-yl ester and (2) α-monoolein) as surface capping/stabilizing agents. Fourier transform infrared (FTIR) analysis of MFLE and MFLE-ZnONPs showed the association of amines, alkanes, aldehydes, amides, carbonyl and amines functional groups in the corona formation. Overall, our data provide novel insights on the rapid development of eco-friendly, cost-effective bio-synthesis of MFLE-ZnONPs, showing their putative application as nano-antibiotics against MDR clinical isolates.


Asunto(s)
Ésteres/farmacología , Nanopartículas del Metal/química , Myristica/metabolismo , Extractos Vegetales/farmacología , Óxido de Zinc/farmacología , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Hojas de la Planta/metabolismo
13.
PLoS One ; 14(4): e0214337, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31013288

RESUMEN

Obesity is connected to the activation of chronic inflammatory pathways in both adipocytes and macrophages located in adipose tissues. The nuclear factor (NF)-κB is a central molecule involved in inflammatory pathways linked to the pathology of different complex metabolic disorders. Investigating the gene expression data in the adipose tissue would potentially unravel disease relevant gene interactions. The present study is aimed at creating a signature molecular network and at prioritizing the potential biomarkers interacting with NF-κB family of proteins in obesity using system biology approaches. The dataset GSE88837 associated with obesity was downloaded from Gene Expression Omnibus (GEO) database. Statistical analysis represented the differential expression of a total of 2650 genes in adipose tissues (p = <0.05). Using concepts like correlation, semantic similarity, and theoretical graph parameters we narrowed down genes to a network of 23 genes strongly connected with NF-κB family with higher significance. Functional enrichment analysis revealed 21 of 23 target genes of NF-κB were found to have a critical role in the pathophysiology of obesity. Interestingly, GEM and PPP1R13L were predicted as novel genes which may act as potential target or biomarkers of obesity as they occur with other 21 target genes with known obesity relationship. Our study concludes that NF-κB and prioritized target genes regulate the inflammation in adipose tissues through several molecular signaling pathways like NF-κB, PI3K-Akt, glucocorticoid receptor regulatory network, angiogenesis and cytokine pathways. This integrated system biology approaches can be applied for elucidating functional protein interaction networks of NF-κB protein family in different complex diseases. Our integrative and network-based approach for finding therapeutic targets in genomic data could accelerate the identification of novel drug targets for obesity.


Asunto(s)
Grasa Intraabdominal/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas de Unión al GTP Monoméricas/genética , Obesidad/genética , Proteínas Represoras/genética , Regulación de la Expresión Génica/genética , Humanos , Inflamación/genética , Inflamación/patología , Sistema de Señalización de MAP Quinasas/genética , Macrófagos/metabolismo , FN-kappa B/genética , Neovascularización Fisiológica/genética , Obesidad/tratamiento farmacológico , Obesidad/patología , Fosfatidilinositol 3-Quinasas/genética , Mapas de Interacción de Proteínas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Receptores de Glucocorticoides/genética
14.
J Biomol Struct Dyn ; 36(10): 2530-2542, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28753123

RESUMEN

Titanium dioxide nanoparticles (TiO2-NPs) interaction with human serum albumin (HSA) and DNA was studied by UV-visible spectroscopy, spectrofluorescence, circular dichroism (CD), and transmission electron microscopy (TEM) to analyze the binding parameters and protein corona formation. TEM revealed protein corona formation on TiO2-NPs surface due to adsorption of HSA. Intrinsic fluorescence quenching data suggested significant binding of TiO2-NPs (avg. size 14.0 nm) with HSA. The Stern-Volmer constant (Ksv) was determined to be 7.6 × 102 M-1 (r2 = 0.98), whereas the binding constant (Ka) and number of binding sites (n) were assessed to be 5.82 × 102 M-1 and 0.97, respectively. Synchronous fluorescence revealed an apparent decrease in fluorescence intensity with a red shift of 2 nm at Δλ = 15 nm and Δλ = 60 nm. UV-visible analysis also provided the binding constant values for TiO2-NPs-HSA and TiO2-NPs-DNA complexes as 2.8 × 102 M-1 and 5.4 × 103 M-1. The CD data demonstrated loss in α-helicity of HSA and transformation into ß-sheet, suggesting structural alterations by TiO2-NPs. The docking analysis of TiO2-NPs with HSA revealed its preferential binding with aromatic and non-aromatic amino acids in subdomain IIA and IB hydrophobic cavity of HSA. Also, the TiO2-NPs docking revealed the selective binding with A-T bases in minor groove of DNA.


Asunto(s)
ADN/química , ADN/metabolismo , Nanopartículas/química , Conformación de Ácido Nucleico , Albúmina Sérica Humana/química , Albúmina Sérica Humana/metabolismo , Titanio/química , Dicroismo Circular , Humanos , Simulación del Acoplamiento Molecular , Nanopartículas/ultraestructura , Unión Proteica , Dominios Proteicos , Espectrometría de Fluorescencia , Espectrofotometría Ultravioleta , Difracción de Rayos X
15.
Microb Pathog ; 111: 375-387, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28916319

RESUMEN

Nanotechnology based therapeutics has emerged as a promising approach for augmenting the activity of existing antimicrobials due to the unique physical and chemical properties of nanoparticles (NPs). Nickel oxide nanoparticles (NiO-NPs) have been suggested as prospective antibacterial and antitumor agent. In this study, NiO-NPs have been synthesized by a green approach using Eucalyptus globulus leaf extract and assessed for their bactericidal activity. The morphology and purity of synthesized NiO-NPs determined through various spectroscopic techniques like UV-Visible, FT-IR, XRD, EDX and electron microscopy differed considerably. The synthesized NiO-NPs were pleomorphic varying in size between 10 and 20 nm. The XRD analysis revealed the average size of NiO-NPs as 19 nm. The UV-Vis spectroscopic data showed a strong SPR of NiO-NPs with a characteristic spectral peak at 396 nm. The FTIR data revealed various functional moieties like C=C, C-N, C-H and O-H which elucidate the role of leaf biomolecules in capping and dispersal of NiO-NPs. The bioactivity assay revealed the antibacterial and anti-biofilm activity of NiO-NPs against ESßL (+) E. coli, P. aeruginosa, methicillin sensitive and resistant S. aureus. Growth inhibition assay demonstrated time and NiO-NPs concentration dependent decrease in the viability of treated cells. NiO-NPs induced biofilm inhibition was revealed by a sharp increase in characteristic red fluorescence of PI, while SEM images of NiO-NPs treated cells were irregular shrink and distorted with obvious depressions/indentations. The results suggested significant antibacterial and antibiofilm activity of NiO-NPs which may play an important role in the management of infectious diseases affecting human health.


Asunto(s)
Antibacterianos/biosíntesis , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Eucalyptus/química , Níquel/metabolismo , Níquel/farmacología , Extractos Vegetales/química , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Escherichia coli/fisiología , Eucalyptus/metabolismo , Humanos , Nanopartículas del Metal/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Staphylococcus aureus Resistente a Meticilina/fisiología , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/metabolismo , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/crecimiento & desarrollo , Pseudomonas aeruginosa/fisiología , Espectroscopía Infrarroja por Transformada de Fourier
16.
Sci Rep ; 7: 40685, 2017 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-28120857

RESUMEN

Large-scale synthesis and release of nanomaterials in environment is a growing concern for human health and ecosystem. Therefore, we have investigated the cytotoxic and genotoxic potential of zinc oxide nanoparticles (ZnO-NPs), zinc oxide bulk (ZnO-Bulk), and zinc ions (Zn2+) in treated roots of Allium cepa, under hydroponic conditions. ZnO-NPs were characterized by UV-visible, XRD, FT-IR spectroscopy and TEM analyses. Bulbs of A. cepa exposed to ZnO-NPs (25.5 nm) for 12 h exhibited significant decrease (23 ± 8.7%) in % mitotic index and increase in chromosomal aberrations (18 ± 7.6%), in a dose-dependent manner. Transmission electron microcopy and FT-IR data suggested surface attachment, internalization and biomolecular intervention of ZnO-NPs in root cells, respectively. The levels of TBARS and antioxidant enzymes were found to be significantly greater in treated root cells vis-à-vis untreated control. Furthermore, dose-dependent increase in ROS production and alterations in ΔΨm were observed in treated roots. FT-IR analysis of root tissues demonstrated symmetric and asymmetric P=O stretching of >PO2- at 1240 cm-1 and stretching of C-O ribose at 1060 cm-1, suggestive of nuclear damage. Overall, the results elucidated A. cepa, as a good model for assessment of cytotoxicity and oxidative DNA damage with ZnO-NPs and Zn2+ in plants.


Asunto(s)
Daño del ADN/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Mitocondrias/efectos de los fármacos , Cebollas/efectos de los fármacos , Cebollas/fisiología , Estrés Oxidativo , Raíces de Plantas/efectos de los fármacos , Óxido de Zinc/toxicidad , Aberraciones Cromosómicas/efectos de los fármacos , Cromosomas de las Plantas , Iones/toxicidad , Potencial de la Membrana Mitocondrial , Nanopartículas del Metal/ultraestructura , Mitocondrias/metabolismo , Mitocondrias/ultraestructura , Mitosis/efectos de los fármacos , Oxidación-Reducción , Raíces de Plantas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Espectroscopía Infrarroja por Transformada de Fourier
17.
Environ Toxicol Chem ; 32(12): 2701-10, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23982896

RESUMEN

The present study explored the ecotoxicology of single-walled carbon nanotubes (SWCNTs) and their likely interaction with dissolved metals, with a focus on the effect of in vivo exposure in marine mussels. Any nano-scale effects were negated by the tendency of uncoated SWCNTs to agglomerate in water, particularly with high ionic strength as is the case in estuarine and full-strength seawater. However, SWCNTs, in combination with natural organic matter, remained suspended in seawater for long enough to become available to filter-feeding mussels, leading to their concentration on and increased contact with gill epithelia during exposure. For the first time, the authors describe a potentiating toxicological effect, expressed as DNA strand breaks obtained using the comet assay, on divalent metals afforded by negatively charged SWCNT agglomerates in seawater at concentrations as low as 5 µg L⁻¹. This is supported by the observation that SWCNTs alone were only toxic at concentrations ≥100 µg L⁻¹ and that the SWCNT-induced DNA damage was correlated with oxidative stress only in the absence of metals. If these laboratory experiments are confirmed in the natural environment, the present results will have implications for the understanding of the role of carbon nanotubes in environmental metal dynamics, toxicology, and consequently, regulatory requirements.


Asunto(s)
Metales Pesados/toxicidad , Mytilus edulis/metabolismo , Nanotubos de Carbono/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Ensayo Cometa , Daño del ADN , Metales Pesados/metabolismo , Mytilus edulis/genética , Estrés Oxidativo , Agua de Mar , Contaminantes Químicos del Agua/metabolismo
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