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1.
Sci Rep ; 14(1): 7637, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561394

RESUMO

Rapid placement of electric vehicle charging stations (EVCSs) is essential for the transportation industry in response to the growing electric vehicle (EV) fleet. The widespread usage of EVs is an essential strategy for reducing greenhouse gas emissions from traditional vehicles. The focus of this study is the challenge of smoothly integrating Plug-in EV Charging Stations (PEVCS) into distribution networks, especially when distributed photovoltaic (PV) systems are involved. A hybrid Genetic Algorithm and Simulated Annealing method (GA-SAA) are used in the research to strategically find the optimal locations for PEVCS in order to overcome this integration difficulty. This paper investigates PV system situations, presenting the problem as a multicriteria task with two primary objectives: reducing power losses and maintaining acceptable voltage levels. By optimizing the placement of EVCS and balancing their integration with distributed generation, this approach enhances the sustainability and reliability of distribution networks.

2.
Sci Rep ; 14(1): 3261, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331946

RESUMO

This paper proposes an innovative approach for improving the charging efficiency of electric vehicles (EVs) by combining photovoltaic (PV) systems with AC-DC Power Factor Correction (PFC). The proposed approach employs bi-directional power flow management within the PFC system, allowing for enhanced resource utilization and EV battery capacity under a variety of environmental circumstances. A modified Lyapunov-based robust model reference adaptive controller (M-LRMRAC) is developed to provide real-time Maximum Power Point Tracking (MPPT) for the PV array. By quickly recording the MPP, this controller skilfully adjusts to shifting radiation and temperature dynamics. A noteworthy accomplishment is that the M-LRMRAC outperforms traditional Perturb and Observe (P&O) techniques by achieving quick MPP convergence (0.54 s). Additionally, the benefits of this integrated system go beyond effective MPPT. The method achieves operating at unity power factor and reduces total harmonic distortion, which results in improved power quality when charging EV Batteries (EVB). The entire solution provided by this multifaceted architecture improves the quality of electricity delivered to EV batteries while also increasing energy efficiency. This research helps to the evolution of sustainable and dependable EV charging infrastructure by solving difficulties and optimising performance. The combination of PV systems with AC-DC PFC, aided by the M-LRMRAC technology, presents a viable route for attaining efficient, clean, and high-quality EV charging, hence supporting the shift to a greener and more sustainable transportation landscape.

3.
Sensors (Basel) ; 22(23)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36502009

RESUMO

Recently, there has been an increase in research interest in the seamless streaming of video on top of Hypertext Transfer Protocol (HTTP) in cellular networks (3G/4G). The main challenges involved are the variation in available bit rates on the Internet caused by resource sharing and the dynamic nature of wireless communication channels. State-of-the-art techniques, such as Dynamic Adaptive Streaming over HTTP (DASH), support the streaming of stored video, but they suffer from the challenge of live video content due to fluctuating bit rate in the network. In this work, a novel dynamic bit rate analysis technique is proposed to model client-server architecture using attention-based long short-term memory (A-LSTM) networks for solving the problem of smooth video streaming over HTTP networks. The proposed client system analyzes the bit rate dynamically, and a status report is sent to the server to adjust the ongoing session parameter. The server assesses the dynamics of the bit rate on the fly and calculates the status for each video sequence. The bit rate and buffer length are given as sequential inputs to LSTM to produce feature vectors. These feature vectors are given different weights to produce updated feature vectors. These updated feature vectors are given to multi-layer feed forward neural networks to predict six output class labels (144p, 240p, 360p, 480p, 720p, and 1080p). Finally, the proposed A-LSTM work is evaluated in real-time using a code division multiple access evolution-data optimized network (CDMA20001xEVDO Rev-A) with the help of an Internet dongle. Furthermore, the performance is analyzed with the full reference quality metric of streaming video to validate our proposed work. Experimental results also show an average improvement of 37.53% in peak signal-to-noise ratio (PSNR) and 5.7% in structural similarity (SSIM) index over the commonly used buffer-filling technique during the live streaming of video.


Assuntos
Redes Neurais de Computação , Gravação em Vídeo/métodos
4.
Biosens Bioelectron ; 204: 114087, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35182836

RESUMO

The nicotinamide adenine dinucleotide-reduced (NADH) function as a hydride (H) carrier to maintain cellular homeostasis. Herein, we report a quinoline appended iridium complex (QAIC) as a molecular probe in fluorescence and surface-enhanced Raman spectroscopy (SERS) modalities to evaluate the endogenous NADH status. NADH-triggered activation of QAIC enabled luminescence (turn-ON) and SERS (turn-OFF) switching phenomenon with a detection limit of 25.6 nM and 15 pM for NADH in luminescence and SERS respectively. Transition state modelling using density functional theory calculations proved that a facile migration of H from NADH to QAIC transformed the activated QAIC (N-QAIC) with an energy span of 19.7 kcal/mol. Furthermore, N-QAIC is probed as a photosensitizer to source singlet oxygen by blocking the photo induced electron transfer (PeT) and generate NAD radicals. Therefore, an efficient light triggered cyclometalated iridium-based molecular probe has been divulged to promote bimodal NADH sensing and multiphase photodynamic therapy.


Assuntos
Técnicas Biossensoriais , Fotoquimioterapia , Irídio/química , Luminescência , NAD/química
5.
J Control Release ; 339: 284-296, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34610379

RESUMO

Carbohydrate-lectin interactions and glycol-molecule-driven self-assembly are powerful yet challenging strategies to create supramolecular nanostructures for biomedical applications. Herein, we develop a modular approach of micellization with a small molecular mannosylated-calix[4]arene synthetic core, CA4-Man3, to generate nano-micelles, CA4-Man3-NPs, which can target cancer cell surface receptors and facilitate the delivery of hydrophobic cargo. The oligomeric nature of the calix[4]arene enables the dynamic self-assembly of calix[4]arene (CA4), where an amphiphile, functionalized with mannose units (CA-glycoconjugates) in the upper rim and alkylated lower rim, afforded the CA4-Man3-NPs in a controllable manner. The presence of thiourea units between calixarene and tri-mannose moiety facilitated the formation of a stable core with bidentate hydrogen bonds, which in turn promoted mannose receptor targeted uptake and helped in the intracellular pH-responsive release of antineoplastic doxorubicin (Dox). Physiochemical features including the stability of the nanomicelle could circumvent the undesirable leakage of the cargoes, ensuring maximum therapeutic output with minimum off-targeted toxicity. Most importantly, surface-enhanced Raman scattering (SERS) was utilized for the first time to evaluate the critical micelle concentration during the formation, cellular uptake and intracellular drug release. The present study not only provides an architectural design of a new class of organic small molecular nanomicelles but also unveils a robust self-assembly approach that paves the way for the delivery of a wide range of hydrophobic chemotherapeutic drugs.


Assuntos
Calixarenos , Micelas , Sistemas de Liberação de Fármacos por Nanopartículas , Doxorrubicina , Receptor de Manose , Fenóis
7.
Biofouling ; 37(5): 506-520, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34139900

RESUMO

Marine biogrowth infestation of a seawater intake system was investigated. A digital camera fixed onto a skid was used to record the biogrowth at intervals of 5 m up to a depth of 55 m. Divers inspected the intake shaft and collected the biogrowth samples for biomass estimation. A biomass density of 7.5 kg m-2 and 28.2 kg m-2 was recorded at 5 and 30 m depths respectively. Inspection by the divers revealed that hard-shelled organisms such as oysters and brown and green mussels were observed in plenty up to a thickness of 15 cm and bryozoans grew as epibionts. At lower depths (<40 m), hydroids grew on the shells of green mussels along with silt accumulation. The biofouling community was composed of 46 organisms, exhibiting variation in distribution and abundance. The study explains the extent and type of marine biogrowth phenomena with depth and describes biofouling preventive methods.Supplemental data for this article is available online at https://doi.org/10.1080/08927014.2021.1933457 .


Assuntos
Incrustação Biológica , Bivalves , Animais , Biomassa , Água do Mar
8.
Pain Physician ; 24(1): E37-E44, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33400436

RESUMO

BACKGROUND: Topical morphine along with intrasite gel has been proven to be a simple and effective method to relieve pain. However, morphine is still not freely available in developing countries due to drug restrictions and stringent laws governing it. Loperamide has been reported to relieve pain caused by stomatitis effectively when given topically. Loperamide, being an mu receptor agonist with no systemic absorption, can serve a dual purpose here. Also loperamide being freely available as an over-the-counter drug can be a surrogate drug for topical application. OBJECTIVES: The primary aim was to compare the efficacy of loperamide and morphine in treating pain when applied topically along with intrasite gel. STUDY DESIGN: Adult patients with healthy wounds with pain on Numeric Rating Scale (NRS-11) greater than 5 with no systemic comorbid illness were divided randomly into 2 groups - group morphine or group loperamide - for 24 hours followed by a 1-day washout and crossover in the other group for 24 hours. Pain was assessed once every day. SETTING: Medical college and hospital. METHODS: The parameters assessed included: (1) characteristics of the ulcer; (2) pain was assessed by NRS-11 at 12-hour intervals for a period of 72 hours; and (3) patient satisfaction. Statistical analysis used repeated measures analysis of variance to measure change in mean NRS-11 within each group. Analysis of covariance was used to compare the mean change in NRS-11 in the 2 groups. RESULTS: Morphine and loperamide were equivocal in pain relief after 12 and 24 hours (P = 0.400 and P = 0.753); however, the patient satisfaction scores were better in the morphine group. LIMITATIONS: The earlier studies performed used injectable forms of morphine, for the sake of comparison, we used powdered morphine and powdered Loperamide diluted with saline. Confounding variables include ulcer size and aetiology, which can be a source of bias. The ulcer size was not standardized due to the paucity of sample to study. Equianalgesic doses of loperamide and morphine could not be found even after an extensive literature search. The loperamide dose used in our case was equal to the dose used orally since the same dose appears effective across a range of oral opioid analgesics. The morphine dose was standardized as 10 mg based on a mixture previously used to treat pain due to epidermolysis bullosa. CONCLUSIONS: Topical loperamide can be an efficacious and novel intervention to treat painful ulcers while avoiding systemic effects.


Assuntos
Analgésicos/uso terapêutico , Hidrogéis/uso terapêutico , Loperamida/uso terapêutico , Morfina/uso terapêutico , Úlcera Cutânea/tratamento farmacológico , Adulto , Estudos Cross-Over , Estudos de Viabilidade , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Manejo da Dor/métodos , Projetos Piloto
10.
ACS Appl Mater Interfaces ; 12(39): 43365-43379, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32880178

RESUMO

In an attempt to circumvent the major pitfalls associated with conventional chemotherapy including drug resistance and off-target toxicity, we have adopted a strategy to simultaneously target both mitochondrial DNA (Mt-DNA) and nuclear DNA (n-DNA) with the aid of a targeted theranostic nanodelivery vehicle (TTNDV). Herein, folic acid-anchored p-sulfo-calix[4]arene (SC4)-capped hollow gold nanoparticles (HGNPs) were meticulously loaded with antineoplastic doxorubicin (Dox) and its mitochondrion-targeted analogue, Mt-Dox, in a pretuned ratio (1:100) for sustained thermoresponsive release of cargo. This therapeutic strategy was enabled to eradicate both n-DNA and Mt-DNA leaving no space to develop drug resistance. The SC4-capped HGNPs (HGNPSC4) were experimented for the first time as a photothermal (PTT) agent with 61.6% photothermal conversion efficiency, and they generated tunable localized heat more efficiently than bare HGNPs. Moreover, the cavity of SC4 facilitated the formation of an inclusion complex with folic acid to target the folate receptor expressing cancer cells and imparted enhanced biocompatibility. The as-synthesized TTNDV was demonstrated to be an ideal substrate for surface-enhanced Raman scattering (SERS) to monitor the molecular-level therapeutic progression in cells and a spheroidal model. A significant reduction in the tumor mass with a marked survival benefit was achieved in syngraft murine models through this synergistic photo-chemotherapy. Collectively, this multifunctional nanoplatform offers a robust approach to treat cancer without any scope of generating Dox resistance and off-target toxicity.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Temperatura , Animais , Antibióticos Antineoplásicos/química , Calixarenos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , DNA Mitocondrial/efeitos dos fármacos , DNA de Neoplasias/efeitos dos fármacos , Doxorrubicina/química , Portadores de Fármacos/química , Ensaios de Seleção de Medicamentos Antitumorais , Ácido Fólico/química , Ouro/química , Humanos , Masculino , Nanopartículas Metálicas/química , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Tamanho da Partícula , Fenóis/química , Fármacos Fotossensibilizantes/química , Propriedades de Superfície
11.
Small ; 16(38): e2003309, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32797715

RESUMO

The downsides of conventional cancer monotherapies are profound and enormously consequential, as drug-resistant cancer cells and cancer stem cells (CSC) are typically not eliminated. Here, a targeted theranostic nano vehicle (TTNV) is designed using manganese-doped mesoporous silica nanoparticle with an ideal surface area and pore volume for co-loading an optimized ratio of antineoplastic doxorubicin and a drug efflux inhibitor tariquidar. This strategically framed TTNV is chemically conjugated with folic acid and hyaluronic acid as a dual-targeting entity to promote folate receptor (FR) mediated cancer cells and CD44 mediated CSC uptake, respectively. Interestingly, surface-enhanced Raman spectroscopy is exploited to evaluate the molecular changes associated with therapeutic progression. Tumor microenvironment selective biodegradation and immunostimulatory potential of the MSN-Mn core are safeguarded with a chitosan coating which modulates the premature cargo release and accords biocompatibility. The superior antitumor response in FR-positive syngeneic and CSC-rich human xenograft murine models is associated with a tumor-targeted biodistribution, favorable pharmacokinetics, and an appealing bioelimination pattern of the TTNV with no palpable signs of toxicity. This dual drug-loaded nano vehicle offers a feasible approach for efficient cancer therapy by on demand cargo release in order to execute complete wipe-out of tumor reinitiating cancer stem cells.


Assuntos
Nanopartículas , Neoplasias , Animais , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Resistência a Medicamentos , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Células-Tronco Neoplásicas , Medicina de Precisão , Dióxido de Silício/uso terapêutico , Distribuição Tecidual , Microambiente Tumoral
12.
Nanomedicine ; 29: 102276, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32736038

RESUMO

Herein we have stepped-up on a strategic spectroscopic modality by utilizing label free ultrasensitive surface enhanced Raman scattering (SERS) technique to generate a differential spectral fingerprint for the prediction of normal (NRML), high-grade intraepithelial lesion (HSIL) and cervical squamous cell carcinoma (CSCC) from exfoliated cell samples of cervix. Three different approaches i.e. single-cell, cell-pellet and extracted DNA from oncology clinic as confirmed by Pap test and HPV PCR were employed. Gold nanoparticles as the SERS substrate favored the increment of Raman intensity exhibited signature identity for Amide III/Nucleobases and carotenoid/glycogen respectively for establishing the empirical discrimination. Moreover, all the spectral invention was subjected to chemometrics including Support Vector Machine (SVM) which furnished an average diagnostic accuracy of 94%, 74% and 92% of the three grades. Combined SERS read-out and machine learning technique in field trial promises its potential to reduce the incidence in low resource countries.


Assuntos
Carcinoma in Situ/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Carcinoma in Situ/patologia , Carcinoma in Situ/virologia , Carcinoma de Células Escamosas/patologia , Citodiagnóstico/métodos , Diagnóstico Diferencial , Feminino , Ouro/química , Ouro/uso terapêutico , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/virologia , Análise Espectral Raman/métodos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
13.
Nanoscale ; 12(13): 6971-6975, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32202584

RESUMO

Precise control over the dynamics of nanoparticles (NPs) in a tumor microenvironment is highly warranted for the development of an efficient nanotheranostic agent. Even though inductively coupled plasma mass spectrometry can provide a quantitative assessment regarding the uptake efficiency of metal NPs, enumeration of deep tissue penetration capacity remains as a challenge. Herein, we have demonstrated an accurate tracking of the uptake efficiency and penetration phenomenon of gold nanoparticles (AuNPs: 40-50 nm) with respect to three different surface charges in monolayer (2D) cells, multicellular spheroids (3D) and in vivo tumors by surface-enhanced Raman spectroscopy (SERS). While positively charged AuNPs showed around two-fold increased internalization in monolayer cells, SERS-tag-based line scanning on multi-layered tumor spheroids illustrated almost nine-fold superior penetration capability with negatively charged AuNPs. Further, the enhanced solid tumor distribution contributed by the negatively charged AuNPs could appreciably escalate its clinical utility in cancer management.


Assuntos
Ouro , Nanopartículas Metálicas , Neoplasias Experimentais , Esferoides Celulares , Animais , Ouro/química , Ouro/farmacocinética , Ouro/farmacologia , Células HeLa , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Análise Espectral Raman , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Propriedades de Superfície
14.
ACS Biomater Sci Eng ; 6(1): 235-245, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33463216

RESUMO

Silver nanocrystals have been successfully fabricated by the bioreduction route using the ethanolic extract of Azadirachta indica (neem) leaves as the reducing and capping agent without solvent interference. The silver nanocrystals were grown in a single-step method, without the influence of external energy or surfactants, and at room temperature. The nanoparticles were prepared from different ratios of silver ions to reducing agent molecules and were characterized by UV-vis spectroscopy and transmission electron microscopy (TEM). The nanoparticles were roughly spherical and polydispersed with diameters of less than 40 nm, as determined with high-resolution transmission electron microscopy (HRTEM). Fast Fourier transform (FFT) analysis and X-ray diffraction (XRD) analysis elucidated the crystalline nature of the nanoparticles. The presence of participating functional groups was determined with Fourier transform infrared (FTIR) spectroscopy. The synthesized silver nanoparticles were analyzed as a potential surface-enhanced Raman spectroscopy (SERS) substrate by incorporating rhodamine B as the Raman reporter molecule. The bioreduction process was monitored through SERS fingerprint, which was evaluated by the change in vibrational energies of metal-ligand bonds. It was possible to detect the SERS spectral pattern of the probe molecules on the Ag nanoparticles without the use of any aggregating agent. Thus, the formation of probable intra- and interparticle hot spots was attributed to evaporation-induced aggregation. Furthermore, stirring and precursor salt concentration influenced the kinetics involved in the fabrication process. The thermal stability of the lyophilized nanoparticles prepared from 0.1 M AgNO3 was evaluated with thermogravimetric analysis (TGA) and had a residual mass of 60% at 600 °C. X-ray photoelectron spectroscopy (XPS) studies were used to validate the compositional and chemical-state information. The biomass-capped silver nanoparticles provided antimicrobial activity by inhibiting the growth of Pseudomonas nitroreducens, a biofilm-forming bacterium, and the fungus, Aspergillus unguis (NII 08123).


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Aspergillus , Extratos Vegetais/farmacologia , Pseudomonas , Prata/farmacologia
15.
ACS Biomater Sci Eng ; 6(9): 5254-5263, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-33455274

RESUMO

The design and development of an efficacious tumor-specific drug-delivery system is a challenging task. In this study, we have synthesized target-specific small peptide substrates on an octaguanidine sorbitol scaffold, named small molecular targeted drug-delivery conjugate (SMTDDC). The SMTDDC fabrication, with dual targeting cRGD and Cathepsin B (Cath B)-specific tripeptide (Glu-Lys-Phe), altered the microtubule network of glioblastoma cells by the orchestrated release of the cytotoxic paclitaxel (PTX). Cath B assisted PTX delivery was monitored by high-performance liquid chromatography and Surface-Enhanced Raman Scattering (SERS) modalities. The time-dependent SERS fingerprinting and imaging revealed a fast and accurate PTX release profile and subsequent in vitro cytotoxicity as well as the apoptotic events and microtubule network alteration in U-87 MG glioblastoma cells. Furthermore, SMTDDC displayed adequate stability under physiological conditions and demonstrated biocompatibility toward red blood cells and lymphocytes. This study indicated a new insight on SERS-guided peptidomimetic sorbitol molecular transporter, enabling a greater promise with high potential for the further development of PTX delivery in glioblastoma treatment.


Assuntos
Antineoplásicos Fitogênicos , Glioblastoma , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Glioblastoma/tratamento farmacológico , Humanos , Paclitaxel/uso terapêutico
16.
Transgenic Res ; 28(5-6): 573-587, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31599375

RESUMO

EchAMP, the tenth most abundant transcript expressed in the mammary gland of echidna, has in vitro broad-spectrum antibacterial effects. However, the effects of EchAMP on mastitis, a condition where inflammation is triggered following mammary gland infection, has not been investigated. To investigate the impact of EchAMP against mastitis, EchAMP transgenic mice were generated. In antibacterial assays, the whey fractions of milk from transgenic mice significantly reduced growth of Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa compared with whey fractions from wildtype mice. Furthermore, a mastitis model created by infecting mammary gland with these four bacterial strains displayed a significant reduction in bacterial load in transgenic mice injected with S. aureus and B. subtilis. On further confirmation, histomorphologic analysis showed absence of necrosis and cell infiltration in the mammary glands of transgenic mice. To understand the role of EchAMP against inflammation, we employed an LPS-injected mastitis mouse model. LPS is known to induce phopshorylation of NF-κB and MAPK pathways, which in turn activate downstream proinflammatory signaling mediators, to promote inflammation. In LPS-treated EchAMP transgenic mice, phosphorylation levels of NF-κB, p38 and ERK1/2 were significantly downregulated. Furthermore, in mammary gland of transgenic mice, there was a significant downregulation of mRNA levels of proinflammatory cytokines, namely TNF-α, IL-6 and IL-1ß. Taken together, these data suggest that EchAMP has an antiinflammatory response and is effective against S. aureus and B. subtilis. We suggest that EchAMP may be a potential prophylactic protein against mastitis in dairy animals by expressing this gene in their mammary gland.


Assuntos
Peptídeos Catiônicos Antimicrobianos/genética , Inflamação/genética , Mastite/genética , Infecções Estafilocócicas/genética , Animais , Feminino , Humanos , Inflamação/induzido quimicamente , Inflamação/microbiologia , Inflamação/prevenção & controle , Interleucina-1beta/genética , Interleucina-6/genética , Lipopolissacarídeos/toxicidade , Sistema de Sinalização das MAP Quinases/genética , Glândulas Mamárias Animais/metabolismo , Mastite/induzido quimicamente , Mastite/microbiologia , Mastite/prevenção & controle , Camundongos , Camundongos Transgênicos/genética , NF-kappa B/genética , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade , Tachyglossidae/genética , Fator de Necrose Tumoral alfa/genética
17.
J Med Chem ; 62(17): 8311-8329, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31393121

RESUMO

Hydnocarpin (Hy) is a flavonoid isolated and purified from the seeds of Hydnocarpus wightiana Blume. Herein, we have developed a built-in semi-synthetic modification on Hy by one-pot multi-component reaction and a [3 + 2] cycloaddition strategy to append five membered isoxazole and isoxazolone as new phytochemical entities (NPCEs). Two selected NPCEs viz Hy-ISO-VIII and Hy-ISO-G from the library of 20 newly synthesized derivatives after in vitro screening unveiled promising cytotoxicity and induced caspase-mediated apoptosis against the human lung and melanoma cancer cells which were well supported by virtual screening based on ligand binding affinity and molecular dynamic simulations. As a new insight, we introduced surface-enhanced Raman spectroscopy to identify the chemo-marker molecular fingerprint to confirm the cellular uptake, cytochrome c release, and DNA fragmentation in a label-free manner. The present findings throw up a surfeit of seminal reasons behind the semi-synthetic modification of Hy, stepping forward to cancer chemotherapy.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Citocromos c/antagonistas & inibidores , Flavonolignanos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Melanoma/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Reação de Cicloadição , Citocromos c/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Flavonolignanos/síntese química , Flavonolignanos/química , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Melanoma/metabolismo , Melanoma/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais Cultivadas
18.
ACS Appl Bio Mater ; 2(1): 588-600, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35016322

RESUMO

Effective treatment of malignant melanoma requires an appropriate combination of therapeutic intervention with long-term prognosis as it often survives by monotherapies. Herein, we report a novel melanoma-targeted theranostic nanoenvelope (MTTNe: ISQ@BSA-AuNC@AuNR@DAC@DR5) which has been constructed by assembling a bovine serum albumin (BSA) stabilized gold nanocluster on a gold nanorod (BSA-AuNC@AuNR), a three-in-one theranostic modality, i.e., photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy, tethered with a surface-enhanced Raman scattering (SERS) detection technique. The resultant MTTNe was coloaded with the melanoma-specific FDA approved drug dacarbazine (DAC) and a newly synthesized near-infrared (NIR) absorbing squaraine molecule ISQ that served partly as a photosensitizer and multiplex Raman reporter. Finally, a nanoenvelope was anchored with anti-DR5 monoclonal antibodies as a targeting motif for highly expressed melanoma-specific death receptors in malignant cells. Significant phototherapies of MTTNe were initiated upon an 808 nm single laser trigger which showed a synergistic effect of photothermal hyperthermia as well as singlet oxygen (1O2) driven photodynamic effect in the presence of ISQ followed by on-demand thermoresponsive drug release in the intracellular milieu. Moreover, a multiplex SERS spectral pattern of ISQ (1345 cm-1) and DAC (1269 cm-1) has been utilized for monitoring precise drug release kinetics and target-specific recognition on melanoma cells by Raman imaging. Therapeutic performance of the nanoenvelope was evaluated by in vitro cytotoxicity studies in human melanoma cells (A375) and confirmed the apoptotic phenomenon by molecular-level monitoring of intracellular SERS fingerprints. Finally, to address the biocompatibility of MTTNe, in vivo subacute toxicity was conducted on BALB/c mice. Hence, the current studies mark a footstep of a facile strategy for the treatment of melanoma by synergistic multimodal photothermal/photodynamic/chemotherapy.

19.
Nutr Diabetes ; 8(1): 57, 2018 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-30369599

RESUMO

Type I diabetes, though contributes to only 5-10% of total diabetes cases, is a rising concern in today's world. Our previous studies have shown that the absence of WDR13 in mouse results in pancreatic ß-cell hyper-proliferation. Also, amelioration of the diabetic phenotype on introgression of Wdr13-null (Wdr13-/0) mutation in genetically diabetic mice (Leprdb/db) [type II diabetes] was observed. It was thus, interesting to see the role of WDR13 in streptozotocin-mediated diabetes in mice, a model for type I diabetes. Wdr13-/0 mice along with its wild type (Wdr13+/0 mice) littermates were administered streptozotocin intraperitoneally for 5 consecutive days. Blood glucose levels and body weights of these mice were monitored for subsequent 5 weeks and then they were sacrificed for physiological and histological analyses. Results showed that Wdr13-/0 mice exhibited higher serum insulin levels, better glucose clearance and significantly higher number of proliferating ß-cells; reiterating the finding that absence of WDR13 helps in ß-cell hyper-proliferation and recovery from diabetes; further underscoring WDR13 as a key target molecule for diabetes treatment/amelioration.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Insulina/sangue , Proteínas Nucleares/metabolismo , Animais , Peso Corporal/fisiologia , Proteínas de Ciclo Celular , Proliferação de Células , Diabetes Mellitus Experimental/genética , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Camundongos Knockout , Proteínas Nucleares/genética
20.
ACS Appl Mater Interfaces ; 10(45): 38807-38818, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30353718

RESUMO

Comprehensive profiling of multiple protein targets plays a critical role in deeper understanding of specific disease conditions associated with high heterogeneity and complexity. Herein, we present the design and fabrication of smart programmable nanoarchitectures, which could integrate clinically relevant diagnostic modalities for the multiplexed detection of most prevalent panel of disease biomarkers present in lung cancer. The multiplex nanoprobes were prepared by attaching dual-functional Raman-active fluorogens onto spherical gold nanoparticles through a peptide linker, Phe-Lys-Cys (FKC), which is engineered with a cathepsin B (cathB) enzyme cleavage site. The presence of cathB induces the scission of FKC upon homing into the cancer cells, resulting in the release of the initially latent fluorophores with a concomitant quenching of the surface-enhanced Raman signal intensity, thereby realizing an on-off switching between the fluorescence and Raman modalities. The enzyme-triggered switchable nanoprobes were utilized for the simultaneous detection of pathologically relevant lung cancer targets by tethering with specific antibody units. The multiplex-targeted multicolor coded detection capability of the antitags was successfully developed as a valid protein screening methodology, which can address the unmet challenges in the conventional clinical scenario for the precise and early diagnosis of lung cancer.


Assuntos
Adenocarcinoma de Pulmão/química , Biomarcadores Tumorais/análise , Catepsina B/química , Corantes Fluorescentes/química , Análise Espectral Raman/métodos , Células A549 , Adenocarcinoma de Pulmão/diagnóstico , Linhagem Celular Tumoral , Ouro/química , Humanos , Nanopartículas Metálicas/química , Oligopeptídeos/química , Imagem Óptica/instrumentação , Imagem Óptica/métodos , Sistemas Automatizados de Assistência Junto ao Leito , Análise Espectral Raman/instrumentação
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