Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 86
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Cancer Res ; 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32651255

RESUMO

Inhibition of members of the bromodomain and extra terminal (BET) family of proteins has proven a valid strategy for cancer chemotherapy. All BET identified to date contain two bromodomains (BD; BD1 and BD2) that are necessary for recognition of acetylated lysine residues in the N-terminal regions of histones. Chemical matter that targets BET (BETi) also interact via these domains. Molecular and cellular data indicate that BD1 and BD2 have different biological roles depending upon their cellular context, with BD2 particularly associated with cancer. We have therefore pursued the development of BD2-selective molecules both as chemical probes and as potential leads for drug development. Here we report the structure-based generation of a novel series of tetrahydroquinoline analogs that exhibit >50-fold selectivity for BD2 versus BD1. This selective targeting resulted in engagement with BD-containing proteins in cells, resulting in modulation of MYC proteins and downstream targets. These compounds were potent cytotoxins towards numerous pediatric cancer cell lines and were minimally toxic to non-tumorigenic cells. Additionally, unlike the pan BETi (+)-JQ1, these BD2-selective inhibitors demonstrated no rebound expression effects. Finally, we report a PK-optimized, metabolically stable derivative that induced growth delay in a neuroblastoma xenograft model with minimal toxicity. We conclude that BD2-selective agents are valid candidates for antitumor drug design for pediatric malignancies driven by the MYC oncogene.

2.
J Biomol Struct Dyn ; : 1-11, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32362245

RESUMO

A new strain of a novel infectious disease affecting millions of people, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been declared as a pandemic by the World Health Organization (WHO). Currently, several clinical trials are underway to identify specific drugs for the treatment of this novel virus. The inhibition of the SARS-CoV-2 main protease is necessary for the blockage of the viral replication. Here, in this study, we have utilized a blind molecular docking approach to identify the possible inhibitors of the SARS-CoV-2 main protease, by screening a total of 33 molecules which includes natural products, anti-virals, anti-fungals, anti-nematodes and anti-protozoals. All the studied molecules could bind to the active site of the SARS-CoV-2 protease (PDB: 6Y84), out of which rutin (a natural compound) has the highest inhibitor efficiency among the 33 molecules studied, followed by ritonavir (control drug), emetine (anti-protozoal), hesperidin (a natural compound), lopinavir (control drug) and indinavir (anti-viral drug). All the molecules, studied out here could bind near the crucial catalytic residues, HIS41 and CYS145 of the main protease, and the molecules were surrounded by other active site residues like MET49, GLY143, HIS163, HIS164, GLU166, PRO168, and GLN189. As this study is based on molecular docking, hence being particular about the results obtained, requires extensive wet-lab experimentation and clinical trials under in vitro as well as in vivo conditions.Communicated by Ramaswamy H. Sarma.

3.
Molecules ; 25(10)2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32455592

RESUMO

The extreme lipophilicity of essential oils (EOs) impedes the measurement of their biological actions in an aqueous environment. We formulated oil in water type Pickering Artemisia annua EO nanoemulsions (AEP) with surface-modified Stöber silica nanoparticles (20 nm) as the stabilizing agent. The antimicrobial activity of AEP and its effects on mature Candida biofilms were compared with those of Tween 80 stabilized emulsion (AET) and ethanolic solution (AEE) of the Artemisia EO. The antimicrobial activity was evaluated by using the minimum inhibitory concentrations (MIC90) and minimum effective concentrations (MEC10) of the compounds. On planktonic bacterial and fungal cells beside growth inhibition, colony formation (CFU/mL), metabolic activity, viability, intracellular ATP/total protein (ATP/TP), along with reactive oxygen species (ROS) were also studied. Artemisia annua EO nanoemulsion (AEP) showed significantly higher antimicrobial activity than AET and AEE. Artemisia annua EO nanoemulsions (AEP) generated superoxide anion and peroxides-related oxidative stress, which might be the underlying mode of action of the Artemisia EO. Unilamellar liposomes, as a cellular model, were used to examine the delivery efficacy of the EO of our tested formulations. We could demonstrate higher effectiveness of AEP in the EO components' donation compared to AET and AEE. Our data suggest the superiority of the AEP formulation against microbial infections.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32447735

RESUMO

Urbanized rivers flowing through polluted megacities receive substantial amount of carbon from domestic sewage and industrial effluents which can significantly alter the air-water CO2 flux rates. In this regard, we quantified the partial pressure of CO2 in the surface water (pCO2(water)), air-water CO2 fluxes, and associated biogeochemical parameters in the Hooghly River, India, flowing through two of the most polluted cities of the country, Kolkata and Howrah, over a complete annual cycle during spring tidal phase (SP) and neap tidal phase (NP). This urbanized part of Hooghly River was always supersaturated with CO2 having an annual mean pCO2(water) and air-water CO2 flux of ~ 3800 µatm and ~ 49 mol C m-2 year-1, respectively. Significant seasonal variability was observed for both pCO2(water) and air-water CO2 flux (pre-monsoon, 3038 ± 539 µatm and 5049 ± 964 µmol m-2 h-1; monsoon, 4609 ± 711 µatm and 7918 ± 1400 µmol m-2 h-1; post-monsoon, 2558 ± 258 µatm and 4048 ± 759 µmol m-2 h-1, respectively). Monthly mean pH and total alkalinity varied from 7.482 to 8.099 and from 2437 to 4136 µmol kg-1, respectively, over the annual cycle. pCO2(water) showed significant positive correlation with turbidity and negative correlation with electrical conductivity and gross primary productivity (GPP). High water discharge could have facilitated high turbidity, especially during the monsoon season, which led to depletion in GPP and enhancement in pCO2(water) which in turn led to very high CO2 effluxes. The CO2 efflux rate in this urbanized riverine stretch was substantially higher than that observed in previous studies carried out in the less urbanized estuarine stretch of Hooghly. This indicates that the presence of highly urbanized and polluted metropolis potentially enhanced the pCO2(water) and CO2 effluxes of this river. Similar observations were made recently in some Asian and Australian urban rivers.

5.
Nanoscale ; 12(14): 7604-7621, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32232245

RESUMO

In recent days, vanadium complexes and nanoparticles have received sustainable attention owing to their vast applications in different fields. In the present study, we report a facile approach for the synthesis of irregular dumbbell shaped vanadium pentoxide nanoparticles (V2O5 NPs: 30-60 nm) via the polyol-induced microwave irradiation process along with calcination. The as-synthesized nanoparticles were characterized using various physico-chemical techniques (e.g. XRD, TEM, FT-IR, DLS and XPS). The cell viability assay showed that V2O5 NPs could efficiently inhibit the proliferation of different cancer cells (B16F10, A549, and PANC1), depicting their anti-proliferative activity. However, V2O5 NPs did not exert significant cytotoxicity to the normal cells (CHO, HEK-293 and NRK-49F), suggesting their biocompatible nature. Interestingly, these nanoparticles inhibited the proliferation and migration of the endothelial cells (HUVECs and EA.hy926) and disrupted the blood vasculature in a chick embryo model, indicating their anti-angiogenic properties. The mechanistic study revealed that the effective internalization of V2O5 NPs generated intracellular reactive oxygen species (ROS) which in turn up-regulated p53 protein and down-regulated survivin protein in cancer cells, leading to the apoptosis process. Furthermore, the administration of V2O5 NPs to melanoma bearing C57BL6/J mice significantly increased their survivability as compared to the control untreated tumor bearing mice, exhibiting the therapeutic potential of the nanoparticles against melanoma. Additionally, the in vivo toxicity study demonstrated no toxic effect in mice upon sub-chronic exposure to V2O5 NPs. Altogether, we strongly believe that V2O5 NPs could intrinsically provide a new direction for alternative therapeutic treatment strategies for melanoma and other cancers by employing their anti-angiogenic properties in the future.

6.
Asian J Psychiatr ; 51: 101967, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32114115

RESUMO

OBJECTIVE: Association between leptin plasma levels and alcohol craving has been seen previously. This study aims to research this correlation in a different population while comparing this correlation with respect to hyper-excitable state of alcohol withdrawal. METHODS: 25 patients of alcohol dependence were assessed for withdrawal symptoms and craving for alcohol. Leptin levels were measured on 1st day, @ the end of 1st week, @ the end of 3rd week of stopping alcohol. Withdrawal was assessed using CIWA-A at day 1 and day 7, craving was assessed using PENN's scale of craving at week 1 and week 3. Control group consisted of 15 first degree relatives. RESULTS: Leptin levels [t (38) = 2.95, p = 0.005] was significantly higher in alcohol dependent patients. Levels had no significant correlation with alcohol withdrawal scores [Leptin/BMI and CIWA Ar: r = 0.18, p = 0.40 on day 1] but had positive correlation with craving scores [Leptin/BMI and PACS: r = 0.684, p = 0.001]. CONCLUSION: This study shows that leptin, known for balancing the energy homeostasis of body, also seem to play a role in pathways of drug dependence and craving. This relation is independent of stress hormone axis.

7.
Environ Sci Pollut Res Int ; 27(15): 18182-18195, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32170622

RESUMO

Aquaculture practices are steadily increasing to meet the fish demand, especially in tropical countries like India. However, efforts to characterize the contribution of these aquaculture ponds towards greenhouse gas emission like CH4 are still very few. CH4 concentration in water [pCH4(water)] and air-water CH4 fluxes were estimated (during the summer months) in two sewage-fed ponds having different depths situated in the East Kolkata Wetlands, India (a Ramsar site). pCH4(water) in both of these ponds showed significant positive correlation with water temperature (R2 = 0.68 and 0.71, p < 0.05). Daily mean chlorophyll-a, turbidity, biochemical oxygen demand (BOD) and gross primary productivity (GPP) also showed positive correlation with pCH4(water). This indicated that higher primary production and presence of turbid materials acted as substrates for methanogenesis, which favoured air-water CH4 effluxes towards atmosphere. Mean air-water CH4 fluxes in the ponds having depth of 1.1 m and 0.6 m were observed to be 24.79 ± 12.02 mg m-2 h-1 and 6.05 ± 3.14 mg m-2 h-1 respectively. Higher depth facilitated net heterotrophic conditions, which led to lower dissolved oxygen levels, which, in turn, led to lower rate of CH4 oxidation. Moreover, under reduced photosynthetically active radiation (in the pond having greater depth), the pH values were comparatively lower (~7.7), which further facilitated a favourable condition for the methanogens to grow. On the whole, it was inferred that apart from pre-established physicochemical factors, depth was also found to play a decisive role in regulating the air-water CH4 fluxes from these aquaculture ponds. In future, continuous sampling should be carried out (by chamber method) to take into account the ebullition CH4 fluxes, and more number of ponds should be sampled throughout a complete annual cycle to have a more holistic understanding about this cluster of sewage-fed aquaculture ponds.


Assuntos
Poluentes Atmosféricos/análise , Metano/análise , Animais , Aquicultura , Dióxido de Carbono/análise , Índia , Tanques , Esgotos , Água
8.
J Photochem Photobiol B ; 205: 111825, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32142995

RESUMO

In recent years research based on kaempferol (KMP) has shown its potential therapeutic applications in medicinal chemistry and clinical biology. Therefore, to understand its molecular recognition mechanism, we studied its interactions with the carrier proteins, namely, human serum albumin (HSA), bovine hemoglobin (BHb) and hen egg white lysozyme (HEWL). The ligand, KMP was able to quench the intrinsic fluorescence of these three proteins efficiently through static quenching mode. The binding constant (Kb) for the interactions of KMP with these three proteins were found in the following order: HSA-KMP > BHb-KMP > HEWL-KMP. Different non-covalent forces such as hydrogen bonding and hydrophobic forces played a major role in the binding of KMP with HSA and HEWL, whereas hydrogen bonding and van der Waals forces contribute to the complexation of BHb with KMP. KMP was able to alter the micro-environment near the Trp fluorophore of the proteins. KMP altered the secondary structural component of all three proteins. The putative binding sites and the residues surrounding the KMP molecule within the respective protein matrix were determined through molecular docking and molecular dynamics (MD) simulation studies. The conformational flexibility of the ligand KMP and the three individual proteins were also evident from the MD simulation studies.

9.
FASEB J ; 34(4): 4890-4903, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32067270

RESUMO

ATP-binding cassette sub-family G member 2 (ABCG2) is a homodimeric ATP-binding cassette (ABC) transporter that not only has a key role in helping cancer cells to evade the cytotoxic effects of chemotherapy, but also in protecting organisms from multiple xeno- and endobiotics. Structural studies indicate that substrate and inhibitor (ligands) binding to ABCG2 can be differentiated quantitatively by the number of amino acid contacts, with inhibitors displaying more contacts. Although binding is the obligate initial step in the transport cycle, there is no empirical evidence for one amino acid being primarily responsible for ligand binding. By mutagenesis and biochemical studies, we demonstrated that the phylogenetically conserved amino acid residue, F439, was critical for both transport and the binding of multiple substrates and inhibitors. Structural modeling implied that the π-π interactions from each F439 monomer mediated the binding of a surprisingly diverse array of structurally unrelated substrates and inhibitors and that this symmetrical π-π interaction "clamps" the ligand into the binding pocket. Key molecular features of diverse ABCG2 ligands using the π-π clamp along with structural studies created a pharmacophore model. These novel findings have important therapeutic implications because key properties of ligands interacting with ABCG2 have been disovered. Furthermore, mechanistic insights have been revealed by demonstrating that for ABCG2 a single amino acid is essential for engaging and initiating transport of multiple drugs and xenobiotics.

10.
Antioxidants (Basel) ; 9(2)2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32085594

RESUMO

Medicinal plants are widely used in folk medicine but quite often their composition and biological effects are hardly known. Our study aimed to analyze the composition, cytotoxicity, antimicrobial, antioxidant activity and cellular migration effects of Anthyllis vulneraria, Fuchsia magellanica, Fuchsia triphylla and Lysimachia nummularia used in the Romanian ethnomedicine for wounds. Liquid chromatography with mass spectrometry (LC-MS/MS) was used to analyze 50% (v/v) ethanolic and aqueous extracts of the plants' leaves. Antimicrobial activities were estimated with a standard microdilution method. The antioxidant properties were evaluated by validated chemical cell-free and biological cell-based assays. Cytotoxic effects were performed on mouse fibroblasts and human keratinocytes with a plate reader-based method assessing intracellular adenosine triphosphate (ATP), nucleic acid and protein contents and also by a flow cytometer-based assay detecting apoptotic-necrotic cell populations. Cell migration to cover cell-free areas was visualized by time-lapse phase-contrast microscopy using standard culture inserts. Fuchsia species showed the strongest cytotoxicity and the highest antioxidant and antimicrobial activity. However, their ethanolic extracts facilitated cell migration, most probably due to their various phenolic acid, flavonoid and anthocyanin derivatives. Our data might serve as a basis for further animal experiments to explore the complex action of Fuchsia species in wound healing assays.

11.
J Biomol Struct Dyn ; : 1-17, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31900044

RESUMO

The non-enzymatic glycation of plasma proteins by reducing sugars have important consequences on the conformational and functional properties of protein. The formation of advanced glycation end products (AGEs) is responsible for cell death and other pathological conditions. We have synthesized the glycated human serum albumin (gHSA) and characterized the same by using differential spectroscopic measurements. The aim of the present study is to determine the effect of glycation on the binding of human serum albumin (HSA) with bioactive flavonoid chrysin, which possesses anti-cancer, anti-inflammatory and anti-oxidant activities. The interaction of chrysin with HSA and gHSA was studied using multi-spectroscopic, molecular docking and molecular dynamics (MD) simulation techniques. Chrysin quenched the intrinsic fluorescence of both HSA and gHSA by static quenching mechanism. The value of the binding constant (Kb) for the interaction of HSA-chrysin complex (4.779 ± 0.623 × 105 M-1 at 300 K) was found to be higher than that of gHSA-chrysin complex (2.206 ± 0.234 × 105 M-1 at 300 K). Hence, non-enzymatic glycation of HSA significantly reduced its binding affinity towards chrysin. The % α-helicity of HSA was found to get enhanced upon binding with chrysin, and minimal changes were observed for the gHSA-chrysin complex. Site marker probe studies indicated that chrysin binds to subdomain IIA and IIIA of both HSA and gHSA. The results from molecular docking and MD simulation studies correlated well with the experimental findings. Electrostatic interactions followed by hydrogen bonding and hydrophobic interactions played major roles in the binding process. These observations may have some useful insights into the field of pharmaceutics.

12.
Phys Chem Chem Phys ; 22(4): 2212-2228, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31913367

RESUMO

In this work, the interaction of a bioactive tea polyphenol (-)-epigallocatechin gallate (EGCG) with bovine hemoglobin (BHb) along with its anti-oxidative behavior and the anti-glycation property have been explored using multi-spectroscopic and computational techniques. The binding affinity for EGCG towards BHb was observed to be moderate in nature with an order of 104 M-1, and the fluorescence quenching mechanism was characterized by an unusual static quenching mechanism. The binding constant (Kb) showed a continuous enhancement with temperature from 3.468 ± 0.380 × 104 M-1 at 288 K to 6.017 ± 0.601 × 104 M-1 at 310 K. The fluorescence emission measurements along with molecular docking studies indicated that EGCG binds near the most dominant fluorophore of BHb (ß2-Trp37, at the interface of α1 and ß2 chains) within the pocket formed by the α1, α2 and ß2 chains. The sign and magnitude of the thermodynamic parameters, changes in enthalpy (ΔH = +17.004 ± 1.007 kJ mol-1) and in entropy (ΔS = +146.213 ± 2.390 J K-1 mol-1), indicate that hydrophobic forces play a major role in stabilizing the BHb-EGCG complex. The micro-environment around the EGCG binding site showed an increase in hydrophobicity upon ligand binding. The binding of EGCG with BHb leads to a decrease in the α-helical content, whereas that of the ß-sheet increased. FTIR studies also indicated that the secondary structure of BHb changed upon binding with EGCG, along with providing further support for the presence of hydrophobic forces in the complexation process. Molecular docking studies indicated that EGCG binds within the cavity of α1, α2, and ß2 chains surrounded by residues such as α1- Lys99, α1-Thr134, α1-Thr137, α1-Tyr140, α2-Lys127 and ß2-Trp37. Molecular dynamics simulation studies indicated that EGCG conferred additional stability to BHb. Furthermore, moving away from the binding studies, EGCG was found to prevent the glyoxal (GO)-mediated glycation process of BHb, and it was also found to act as a potent antioxidant against the photo-oxidative damage of BHb.


Assuntos
Catequina/análogos & derivados , Hemoglobinas/química , Hemoglobinas/metabolismo , Polifenóis/metabolismo , Animais , Catequina/química , Bovinos , Interações Hidrofóbicas e Hidrofílicas , Simulação de Acoplamento Molecular , Polifenóis/química , Ligação Proteica , Análise Espectral
13.
Molecules ; 25(3)2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31979177

RESUMO

We investigated the antifungal activities of purified plant metabolites artemisinin (Ar) and scopoletin (Sc) including inhibition, effects on metabolic activities, viability, and oxidative stress on planktonic forms and on preformed biofilms of seven Candida species. The characteristic minimum inhibitory concentration (MIC90) of Ar and Sc against Candida species ranged from 21.83-142.1 µg/mL and 67.22-119.4 µg/mL, respectively. Drug concentrations causing ≈10% CFU decrease within 60 minutes of treatments were also determined (minimum effective concentration, MEC10) using 100-fold higher CFUs than in the case of MIC90 studies. Cytotoxic effects on planktonic and on mature biofilms of Candida species at MEC10 concentrations were further evaluated with fluorescent live/dead discrimination techniques. Candida glabrata, Candida guilliermondii, and Candida parapsilosis were the species most sensitive to Ar and Sc. Ar and Sc were also found to promote the accumulation of intracellular reactive oxygen species (ROS) by increasing oxidative stress at their respective MEC10 concentrations against the tested planktonic Candida species. Ar and Sc possess dose-dependent antifungal action but the underlying mechanism type (fungistatic and fungicidal) is not clear yet. Our data suggest that Ar and Sc found in herbal plants might have potential usage in the fight against Candida biofilms.

14.
Cardiovasc Intervent Radiol ; 43(3): 453-458, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31650245

RESUMO

AIM: To investigate potential factors on MR imaging that could be used to predict migration of uterine fibroids post-UAE. METHODS AND MATERIALS: We retrospectively reviewed patients referred for UAE having pre-procedural and 6 months post-procedural MRI, at a tertiary centre, over a 1-year period. Pre- and post-UAE images were reviewed in 64 women by two radiologists to identify the sub-type, dimensions, and infarction rate of each dominant fibroid. The shortest distance between the fibroid and the endometrial wall was measured to determine intramural fibroid movement. Paired sample T tests and two-sample T tests were used to compare between pre- and post-embolization variations and between migrated and non-migrated intramural fibroids, respectively. After preliminary results suggested potential predictors of intramural fibroids migration, we tested our findings against the non-dominant intramural fibroids in the same patients. RESULTS: Review of images revealed 35 dominant intramural fibroids, of which eight migrated to become submucosal fibroids, while five were either partially or completely expelled. These 13 migrated fibroids had a shorter pre-procedural minimum endometrial distance (range 1-2.4 mm) and greater maximum fibroid diameter (range 5.1-18.1 cm), when compared to non-migrating fibroids. On image reassessment, the migrated non-dominant intramural fibroids had a minimum endometrial distance and maximum fibroid diameter within the same range. CONCLUSION: Intramural fibroids with a minimum endometrial distance less than 2.4 mm and a maximum fibroid diameter greater than 5.1 cm have a high likelihood of migrating towards the endometrial cavity after UAE.

15.
ACS Infect Dis ; 6(2): 195-204, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-31775512

RESUMO

Isoxyl (ISO) and thiacetazone (TAC) are two antitubercular prodrugs that abolish mycolic acid biosynthesis and kill Mycobacterium tuberculosis (Mtb) through the inhibition of the essential type II fatty acid synthase (FAS-II) dehydratase HadAB. While mutations preventing ISO and TAC either from being converted to their active form or from covalently modifying their target are the most frequent spontaneous mutations associated with high-level resistance to both drugs, the molecular mechanisms underlying the high-level ISO and TAC resistance of Mtb strains harboring missense mutations in the second, nonessential, FAS-II dehydratase HadBC have remained unexplained. Using a combination of genetic, biochemical, and biophysical approaches and molecular dynamics simulation, we here show that all four reported resistance mutations in the HadC subunit of HadBC alter the stability and/or specific activity of the enzyme, allowing it in two cases (HadBCV85I and HadBCK157R) to compensate for a deficiency in HadAB in whole Mtb bacilli. The analysis of the mycolic acid profiles of Mtb strains expressing the mutated forms of HadC further points to alterations in the activity of the mycolic acid biosynthetic complex and suggests an additional contributing resistance mechanism whereby HadC mutations may reduce the accessibility of HadAB to ISO and TAC. Collectively, our results highlight the importance of developing optimized inhibitors of the dehydration step of FAS-II capable of inhibiting both dehydratases simultaneously, a goal that may be achievable given the structural resemblance of the two enzymes and their reliance on the same catalytic subunit HadB.

16.
Environ Sci Pollut Res Int ; 27(4): 4353-4364, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31832951

RESUMO

Tropical sewage-fed aquaculture ponds of East Kolkata Wetlands (EKW), a Ramsar site, act as deposition center of organic matter and nutrient-rich sewage from the Kolkata metropolis, which in turn is utilized as fish feed in aquaculture ponds. Increasing nutrient load due to multifarious anthropogenic activities usually alters the chlorophyll-a (chl-a) and the partial pressure of carbon dioxide in water [pCO2(water)] dynamics in such aquatic systems. In this regard, the effect of nutrient level alteration [8 times and 24 times, dissolved inorganic nitrogen (DIN) and dissolved inorganic phosphorus (DIP) in addition, respectively] on chl-a and pCO2(water) was tested upon waters of EKW aquaculture ponds in three different seasons by means of microcosm for 8 consecutive days. In both DIN 8× and DIP 8× treatments, an overall increase in chl-a concentrations was observed by the end of experiment; however, in DIN 24× and DIP 24× treatments, chl-a in most of the seasons was found to diminish after a steep rise in its concentration during 4th or 5th day. In all the seasons, the surface waters were supersaturated with CO2 under in situ conditions. The extent of supersaturation enhanced with nutrient addition during monsoon; however, in post-monsoon and pre-monsoon, nutrient addition led to undersaturation of CO2. Though chl-a concentration exhibited substantial variability during the microcosm experiments, the variation in trophic state index was not that much remarkable. In DIN-treated microcosms, uptake rate of DIP was significantly high compared to the reverse scenario, which implied that DIP has a more limiting character than DIN. In P-enriched treatments, the lack of N supplies probably limit production of autotrophic biomass. Thus it can be concluded that the nature of sewage and its DIN/DIP content can significantly alter the primary productivity the CO2 dynamics of such aquaculture ponds in future.


Assuntos
Aquicultura , Dióxido de Carbono/química , Clorofila A/química , Tanques/química , Animais , Biomassa , Nitrogênio/química , Fósforo/química
17.
Mar Pollut Bull ; 143: 101-108, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31789143

RESUMO

This is the first report to assay the heavy metal accumulation in Blue Swimmer Crab in the northern Bay of Bengal. The present study finds that copper (Cu) concentration though has been the highest compared to the other metals, particularly in the gill. Cadmium (Cd) and lead (Pb) have high affinity to be concentrated in Hepatopancreas all through the year. All the metal concentrations were higher during monsoon season (comparatively low salinity) than non-monsoon (high salinity) in the different body parts of Blue swimmer crab i.e. the inverse relationship between accumulation of heavy metals and sea water salinity has been shown. Present study revealed that salinity having the role to accumulate metal in different body parts of Blue Swimmer Crab. In future, microcosm experiments should be done to test the effect of frequent fluctuations of ambient salinity, such as is usual in different seasons in the present study area.


Assuntos
Metais Pesados/farmacocinética , Água do Mar/química , Poluentes Químicos da Água/farmacocinética , Animais , Baías , Braquiúros/efeitos dos fármacos , Braquiúros/metabolismo , Brânquias/química , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Hepatopâncreas/química , Hepatopâncreas/efeitos dos fármacos , Hepatopâncreas/metabolismo , Índia , Metais Pesados/análise , Músculos/química , Músculos/efeitos dos fármacos , Músculos/metabolismo , Salinidade , Estações do Ano , Distribuição Tecidual , Poluentes Químicos da Água/análise
18.
Molecules ; 24(23)2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31779245

RESUMO

Essential oils (EOs) are highly lipophilic, which makes the measurement of their biological action difficult in an aqueous environment. We formulated a Pickering nanoemulsion of chamomile EO (CPe). Surface-modified Stöber silica nanoparticles (20 nm) were prepared and used as a stabilizing agent of CPe. The antimicrobial activity of CPe was compared with that of emulsion stabilized with Tween 80 (CT80) and ethanolic solution (CEt). The antimicrobial effects were assessed by their minimum inhibitory concentration (MIC90) and minimum effective (MEC10) concentrations. Besides growth inhibition (CFU/mL), the metabolic activity and viability of Gram-positive and Gram-negative bacteria as well as Candida species, in addition to the generation of oxygen free radical species (ROS), were studied. We followed the killing activity of CPe and analyzed the efficiency of the EO delivery for examined formulations by using unilamellar liposomes as a cellular model. CPe showed significantly higher antibacterial and antifungal activities than CT80 and CEt. Chamomile EOs generated superoxide anion and peroxide related oxidative stress which might be the major mode of action of Ch essential oil. We could also demonstrate that CPe was the most effective in donation of the active EO components when compared with CT80 and CEt. Our data suggest that CPe formulation is useful in the fight against microbial infections.


Assuntos
Anti-Infecciosos/farmacologia , Camomila/química , Óleos Voláteis/farmacologia , Candida/efeitos dos fármacos , Emulsões/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismo
19.
Phys Chem Chem Phys ; 21(23): 12649-12666, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31157335

RESUMO

In the proposed work, the complexation of bioactive flavonoid luteolin with hen egg white lysozyme (HEWL) along with its inhibitory influence on HEWL modification has been explored with the help of multi-spectroscopic and computational methods. The binding affinity has been observed to be moderate in nature (in the order of 104 M-1) and the static quenching mechanism was found to be involved in the fluorescence quenching process. The binding constant (Kb) shows a progressive increase with the increase in temperature from (4.075 ± 0.046 × 104 M-1) at 293 K to (6.962 ± 0.024 × 104 M-1) at 313 K under experimental conditions. Spectroscopic measurements along with molecular docking calculations suggest that Trp62 is involved in the binding site of luteolin within the geometry of HEWL. The positive changes in enthalpy (ΔH = +19.99 ± 0.65 kJ mol-1) as well as entropy (ΔS = +156.28 ± 2.00 J K-1 mol-1) are indicative of the presence of hydrophobic forces that stabilize the HEWL-luteolin complex. The micro-environment around the Trp residues showed an increase in hydrophobicity as indicated by synchronous fluorescence (SFS), three dimensional fluorescence (3D) and red edge excitation (REES) studies. The % α-helix of HEWL showed a marked reduction upon binding with luteolin as indicated by circular dichroism (CD) and Fourier-transform infrared spectroscopy (FTIR) studies. Moreover, luteolin is situated at a distance of 4.275 ± 0.004 nm from the binding site as indicated by FRET theory, and the rate of energy transfer kET (0.063 ± 0.004 ns-1) has been observed to be faster than the donor decay rate (1/τD = 0.606 ns-1), which is indicative of the non-radiative energy transfer during complexation. Leaving aside the binding study, luteolin showed promising inhibitory effects towards the d-ribose mediated glycation of HEWL as well as towards HEWL fibrillation as studied by fluorescence emission and imaging studies. Excellent correlation with the experimental observations as well as precise location and dynamics of luteolin within the binding site has been obtained from molecular docking and molecular dynamics simulation studies.


Assuntos
Luteolina/química , Luteolina/farmacologia , Muramidase/química , Muramidase/metabolismo , Animais , Sítios de Ligação/efeitos dos fármacos , Galinhas , Fluorescência , Interações Hidrofóbicas e Hidrofílicas , Cinética , Modelos Moleculares , Estrutura Molecular , Termodinâmica
20.
Biomater Sci ; 7(7): 2652-2674, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31094374

RESUMO

Chronic wounds have emerged as a major cause of mortality, especially in patients with diabetes and other pathologies. Statistics indicate that chronic wounds affect around 6.5 million patients annually, with wound care and management incurring huge economic costs. Growing incidence of chronic wounds and associated pathologies along with the limitations of current therapies have established a strong need for novel and innovative approaches to accelerate wound healing. Conventionally, chronic wounds are addressed using various FDA-approved silver-based formulations and other biomaterials. However, the toxicity associated with these conventional approaches, along with the increased frequency of chronic wound cases, makes the development of alternative therapies for effective wound healing necessary. Recently, researchers have investigated the design and development of nanoparticles, especially inorganic metal nanoparticles, as promising candidates for addressing various pathological conditions, including wound healing. Several research groups, including ours, have designed numerous metal nanoparticles (including silver, gold, zinc oxide, cerium oxide, terbium hydroxide, silica, titanium oxide, copper) and demonstrated their wound-healing properties using in vitro and in vivo models. The rise of nanotechnology-based platforms in wound healing is evidenced by the tremendous impact and number of publications observed in recent years, which has emphasized the robust potential of inorganic nanomedicine for addressing wounds. Therefore, the importance of these inorganic nanomaterial-based interventions for wound-healing applications needs to be emphasized to inform and encourage scientists and young researchers globally to engage with this expanding area of biology and medicine. In this review article, we mainly focus on highlighting the role of inorganic nanomaterials and nanomaterial-based approaches for wound healing and tissue regeneration, along with their mechanistic properties, clinical status, challenges, and future directions.


Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Nanoestruturas , Nanotecnologia/métodos , Cicatrização/efeitos dos fármacos , Animais , Humanos , Neovascularização Fisiológica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA