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1.
PLoS One ; 19(4): e0300467, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38593146

RESUMO

Liposome nanoparticles can carry a wide range of therapeutic molecules including small molecules and nucleic acid-based therapeutics. Potential benefits include translocation across physiological barriers, reduced systemic toxicity, and enhanced pharmacokinetic parameters such as absorption, distribution, selective release and optimal elimination kinetics. Liposome nanoparticles can be generated with a wide range of natural and synthetic lipid-based molecules that confer desirable properties depending on the desired therapeutic application Nel et al (2023), Large (2021), Elkhoury (2020). This protocol article seeks to detail the procedures involved in the production of cationic liposomes using thin-film dispersed hydration method with an estimated uniform size of 60-70 nm for targeted drug administration in tumor cells, by modifying the previous one also published by the same authors cited here. The method was carrying out using N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl (DOTAP, 2 mg) as cationic lipid and cholesterol (0.5 mg) in a molar ratio of 7:3 respectively. The liposomal suspension was obtained and its physical, chemical and biological properties were determined. A two-step extrusion process, using 100 nm and 50 nm polycarbonate membranes, was carried. The results demonstrate generation of liposome nanoparticles with a size of 60-70 nm stable for at least 16 weeks and with an encapsulation efficiency of approximately 81% using Doxorubicin.


Assuntos
Nanopartículas , Ácidos Nucleicos , Lipossomos/química , Nanopartículas/química , Doxorrubicina , Lipídeos/química
2.
Sci Rep ; 14(1): 6214, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486008

RESUMO

Fucoidan has attracted considerable attention from scientists and pharmaceutical companies due to its antioxidant, anticoagulant, anti-inflammatory, anti-tumor, and health-enhancing properties. However, the extraction of fucoidan from seaweeds often involves the use of harsh chemicals, which necessitates the search for alternative solvents. Additionally, the high viscosity and low cell permeability of high molecular weight (Mw) fucoidan can limit its effectiveness in drug action, while lower Mw fractions exhibit increased biological activity and are also utilized as dietary supplements. The study aimed to (1) extract fucoidan from the seaweed Fucus vesiculosus (FV) using an environmentally friendly solvent and compare it with the most commonly used extraction solvent, hydrochloric acid, and (2) assess the impact of ultrasound-assisted depolymerization on reducing the molecular weight of the fucoidan extracts and examine the cytotoxic effect of different molecular weight fractions. The findings indicated that the green depolymerization solvent, in conjunction with a brief ultrasound treatment, effectively reduced the molecular weight. Moreover, a significant decrease in cell viability was observed in selected samples, indicating potential anticancer properties. As a result, ultrasound was determined to be an effective method for depolymerizing crude fucoidan from Fucus Vesiculosus seaweed.


Assuntos
Fucus , Polissacarídeos , Alga Marinha , Alga Marinha/química , Fucus/química , Anticoagulantes , Solventes
3.
Sensors (Basel) ; 23(24)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38139688

RESUMO

Gliomas, a prevalent category of primary malignant brain tumors, pose formidable clinical challenges due to their invasive nature and limited treatment options. The current therapeutic landscape for gliomas is constrained by a "one-size-fits-all" paradigm, significantly restricting treatment efficacy. Despite the implementation of multimodal therapeutic strategies, survival rates remain disheartening. The conventional treatment approach, involving surgical resection, radiation, and chemotherapy, grapples with substantial limitations, particularly in addressing the invasive nature of gliomas. Conventional diagnostic tools, including computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), play pivotal roles in outlining tumor characteristics. However, they face limitations, such as poor biological specificity and challenges in distinguishing active tumor regions. The ongoing development of diagnostic tools and therapeutic approaches represents a multifaceted and promising frontier in the battle against this challenging brain tumor. The aim of this comprehensive review is to address recent advances in diagnostic tools and therapeutic approaches for gliomas. These innovations aim to minimize invasiveness while enabling the precise, multimodal targeting of localized gliomas. Researchers are actively developing new diagnostic tools, such as colorimetric techniques, electrochemical biosensors, optical coherence tomography, reflectometric interference spectroscopy, surface-enhanced Raman spectroscopy, and optical biosensors. These tools aim to regulate tumor progression and develop precise treatment methods for gliomas. Recent technological advancements, coupled with bioelectronic sensors, open avenues for new therapeutic modalities, minimizing invasiveness and enabling multimodal targeting with unprecedented precision. The next generation of multimodal therapeutic strategies holds potential for precision medicine, aiding the early detection and effective management of solid brain tumors. These innovations offer promise in adopting precision medicine methodologies, enabling early disease detection, and improving solid brain tumor management. This review comprehensively recognizes the critical role of pioneering therapeutic interventions, holding significant potential to revolutionize brain tumor therapeutics.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Glioma/diagnóstico , Glioma/terapia , Glioma/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Encéfalo/patologia , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons/métodos
4.
Foods ; 12(15)2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37569153

RESUMO

Hemp seeds are currently used mainly for oil extraction, generating waste that could be potentially exploited further as a source of proteins and other bioactives. This study aims to valorise hemp waste (Cannabis sativa, L.) from previous oil extraction as a source of protein by analysing the effect of high-pressure processing (HPP) pre-treatments (0-600 MPa; 4-8 min) combined with conventional or ultrasound-assisted extraction (UAE) methods on protein recovery/purity, amino acid composition, and protein structure. Overall, maximum protein recovery (≈62%) was achieved with HPP (200 MPa, 8 min) with UAE. The highest protein purity (≈76%) was achieved with HPP (200 MPa, 4 min) with UAE. Overall, UAE improved the extraction of all amino acids compared to conventional extraction independently of HPP pre-treatments. Arg/Lys ratios of the protein isolates ranged between 3.78 and 5.34, higher than other vegetable protein sources. SDS-PAGE did not show visible differences amongst the protein isolates. These results seem to indicate the advantages of the use of UAE for protein recovery in the food industry and the need for further studies to optimise HPP/UAE for an accurate estimation of processing costs and their effects on the composition and structure of proteins to contribute further to the circular economy.

5.
PLoS One ; 18(2): e0276248, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36753513

RESUMO

Three-dimensional (3D) cell culture models can help bridge the gap between in vitro cell cultures and in vivo responses by more accurately simulating the natural in vivo environment, shape, tissue stiffness, stressors, gradients and cellular response while avoiding the costs and ethical concerns associated with animal models. The inclusion of the third dimension in 3D cell culture influences the spatial organization of cell surface receptors that interact with other cells and imposes physical restrictions on cells in compared to Two-dimensional (2D) cell cultures. Spheroids' distinctive cyto-architecture mimics in vivo cellular structure, gene expression, metabolism, proliferation, oxygenation, nutrition absorption, waste excretion, and drug uptake while preserving cell-extracellular matrix (ECM) connections and communication, hence influencing molecular processes and cellular phenotypes. This protocol describes the in vitro generation of tumourspheroids using the low attachment plate, hanging drop plate, and cellusponge natural scaffold based methods. The expected results from these protocols confirmed the ability of all these methods to create uniform tumourspheres.


Assuntos
Glioblastoma , Animais , Glioblastoma/metabolismo , Técnicas de Cultura de Células/métodos , Esferoides Celulares , Matriz Extracelular/metabolismo
6.
Biomolecules ; 13(2)2023 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-36830755

RESUMO

Seaweed is in the spotlight as a promising source of nutrition for humans as the search for sustainable food production systems continues. Seaweed has a well-documented rich nutritional profile containing compounds such as polyphenols, carotenoids and polysaccharides as well as proteins, fatty acids and minerals. Seaweed processing for the extraction of functional ingredients such as alginate, agar, and carrageenan is well-established. Novel pretreatments such as ultrasound assisted extraction or high-pressure processing can be incorporated to more efficiently extract these targeted ingredients. The scope of products that can be created using seaweed are wide ranging: from bread and noodles to yoghurt and milk and even as an ingredient to enhance the nutritional profile and stability of meat products. There are opportunities for food producers in this area to develop novel food products using seaweed. This review paper discusses the unique properties of seaweed as a food, the processes involved in seaweed aquaculture, and the products that can be developed from this marine biomass. Challenges facing the industry such as consumer hesitation around seaweed products, the safety of seaweed, and processing hurdles will also be discussed.


Assuntos
Alga Marinha , Humanos , Carragenina , Polissacarídeos , Alginatos , Verduras
7.
Drug Discov Today ; 28(2): 103426, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36332834

RESUMO

This review focuses on recent advances in 3D culture systems that promise more accurate therapeutic models of the glioblastoma multiforme (GBM) tumor microenvironment (TME), such as the unique anatomical, cellular, and molecular features evident in human GBM. The key components of a GBM TME are outlined, including microbiomes, vasculature, extracellular matrix (ECM), infiltrating parenchymal and peripheral immune cells and molecules, and chemical gradients. 3D culture systems are evaluated against 2D culture systems and in vivo animal models. The main 3D culture techniques available are compared, with an emphasis on identifying key gaps in knowledge for the development of suitable platforms to accurately model the intricate components of the GBM TME.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Animais , Humanos , Linhagem Celular Tumoral , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Microambiente Tumoral
8.
Mar Drugs ; 20(12)2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36547919

RESUMO

Marine algal species comprise of a large portion of polysaccharides which have shown multifunctional properties and health benefits for treating and preventing human diseases. Laminarin, or ß-glucan, a storage polysaccharide from brown algae, has been reported to have potential pharmacological properties such as antioxidant, anti-tumor, anti-coagulant, anticancer, immunomodulatory, anti-obesity, anti-diabetic, anti-inflammatory, wound healing, and neuroprotective potential. It has been widely investigated as a functional material in biomedical applications as it is biodegradable, biocompatible, and is low toxic substances. The reported preclinical and clinical studies demonstrate the potential of laminarin as natural alternative agents in biomedical and industrial applications such as nutraceuticals, pharmaceuticals, functional food, drug development/delivery, and cosmeceuticals. This review summarizes the biological activities of laminarin, including mechanisms of action, impacts on human health, and reported health benefits. Additionally, this review also provides an overview of recent advances and identifies gaps and opportunities for further research in this field. It further emphasizes the molecular characteristics and biological activities of laminarin in both preclinical and clinical settings for the prevention of the diseases and as potential therapeutic interventions.


Assuntos
Glucanos , Humanos , Glucanos/farmacologia , Polissacarídeos/farmacologia , Preparações Farmacêuticas
9.
Nanomaterials (Basel) ; 12(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36364669

RESUMO

Many polymeric gene delivery nano-vectors with hyperbranched structures have been demonstrated to be superior to their linear counterparts. The higher delivery efficacy is commonly attributed to the abundant terminal groups of branched polymers, which play critical roles in cargo entrapment, material-cell interaction, and endosome escape. Hyperbranched poly(ß-amino ester)s (HPAEs) have developed as a class of safe and efficient gene delivery vectors. Although numerous research has been conducted to optimise the HPAE structure for gene delivery, the effect of the secondary amine residue on its backbone monomer, which is considered the non-ideal termination, has never been optimised. In this work, the effect of the non-ideal termination was carefully evaluated. Moreover, a series of HPAEs with only ideal terminations were synthesised by adjusting the backbone synthesis strategy to further explore the merits of hyperbranched structures. The HPAE obtained from modified synthesis methods exhibited more than twice the amounts of the ideal terminal groups compared to the conventional ones, determined by NMR. Their transfection performance enhanced significantly, where the optimal HPAE candidates developed in this study outperformed leading commercial benchmarks for DNA delivery, including Lipofectamine 3000, jetPEI, and jetOPTIMUS.

10.
Nanomaterials (Basel) ; 12(21)2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36364693

RESUMO

Salmonella is a bacterial pathogen which is one of the leading causes of severe illnesses in humans. The current study involved the design and development of two methods, respectively using iron oxide nanoparticle (IONP) and iron core gold nanoparticle (ICGNP), conjugated with the Salmonella antibody and the fluorophore, 4-Methylumbelliferyl Caprylate (4-MUCAP), used as an indicator, for its selective and sensitive detection in contaminated food products. Twenty double-blind beverage samples, spiked with Salmonella enteritidis, Staphylococcus aureus, and Escherichia coli, were prepared in sterile Eppendorf® tubes at room temperature. The gold layer and spikes of ICGNPs increased the surface areas. The ratio of the surface area is 0.76 (IONPs/ICGNPs). The comparative sensitivity and specificity of the IONP-based and the ICGNP-based methods to detect Salmonella were determined. The ICGNP method shows the limit of detection is 32 Salmonella per mL. The ICGNPs had an 83.3% sensitivity and a 92.9% specificity value for the presence and detection of Salmonella. The IONP method resulted in a limit of detection of 150 Salmonella per mL, and a 66.7% sensitivity and 83.3% specificity for the presence and detection of Salmonella. The higher surface area of ICGNPs increases the efficiency of detection. The monitoring of Salmonella can thus be achieved by a rapid magnetic fluorescent assay using a smartphone for image capture and analyze, providing quantitative results. The findings from the present study would help to detect Salmonella rapidly in water. It can improve the microbial quality of water and food safety due to the presence of Salmonella in the water environment.

11.
PLoS One ; 17(9): e0274524, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36137100

RESUMO

Since first identified in 1879, plasma, the fourth state of matter, has been developed and utilised in many fields. Nonthermal atmospheric plasma, also known as cold plasma, can be applied to liquids, where plasma reactive species such as reactive Oxygen and Nitrogen species and their effects can be retained and mediated through plasma-activated liquids (PAL). In the medical field, PAL is considered promising for wound treatment, sterilisation and cancer therapy due to its rich and relatively long-lived reactive species components. This study sought to identify any potential antagonistic effect between antioxidative intracellularly accumulated platinum nanoparticles (PtNPs) and PAL. We found that PAL can significantly reduce the viability of glioblastoma U-251MG cells. This did not involve measurable ROS influx but instead lead to lipid damage on the plasma membrane of cells exposed to PAL. Although the intracellular antioxidative PtNPs showed no protective effect against PAL, this study contributes to further understanding of principle cell killing routes of PAL and discovery of potential PAL-related therapy and methods to inhibit side effects.


Assuntos
Glioblastoma , Nanopartículas Metálicas , Gases em Plasma , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Morte Celular , Humanos , Peroxidação de Lipídeos , Lipídeos , Nitrogênio , Oxigênio , Gases em Plasma/farmacologia , Platina , Espécies Reativas de Oxigênio/metabolismo
12.
J Sci Food Agric ; 102(14): 6293-6298, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35514139

RESUMO

BACKGROUND: Hempseed meal, a by-product of the hempseed oil processing stream, is a potential alternative source for food proteins. Efficient extraction of proteins from hempseed meal is challenging owing to differences in the structure and solubility of various protein fractions present in the seed. In the present study, protein was extracted from hempseed meal using four different solvents, including aqueous NaOH, KOH, NaHCO3 and NaCl, at four different concentrations with the aim of improving the recovery of protein fractions rich in essential amino acids. RESULTS: Extraction using alkaline solvents provided superior protein recovery (60-78%) compared with NaCl solution and control extractions (20-48% and 21%, respectively). The concentration of alkali or salt (0.25-1 mol L-1 ) had a minor but significant impact on the yield. Amino acid composition analysis revealed that hempseed meal contains 24% (54.5 ± 0.19 mg g-1 ) essential amino acids of total amino acids, and extraction with NaOH, KOH, NaHCO3 or NaCl did not improve the selective extraction of essential amino acids compared to control experiments. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis allowed the identification of edestin and albumin in the extracts obtained with NaHCO3 and NaCl solvents, with results further showing that the type of extraction solvent influences protein extraction selectivity. CONCLUSION: Although alkali solvents provide superior extraction yields, extraction with water resulted in extracts containing the highest proportion of proteins bearing essential amino acids. According to the results of SDS-PAGE, extraction using alkali solvents induced protein crosslinking. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Sementes , Cloreto de Sódio , Albuminas/química , Aminoácidos/análise , Aminoácidos Essenciais/análise , Cannabis , Extratos Vegetais , Sementes/química , Cloreto de Sódio/análise , Dodecilsulfato de Sódio/análise , Hidróxido de Sódio , Solventes/química , Água/análise
13.
Foods ; 11(6)2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35327228

RESUMO

Agar is a hydrocolloid found in red seaweeds, which has been of industrial interest over the last century due to its multiple applications in the food, cosmetic, and medical fields. This polysaccharide, extracted by boiling for several hours, is released from the cell wall of red seaweeds. However, the environmental impact coming from the long processing time and the energy required to reach the targeted processing temperature needs to be reduced. In this study, a response surface methodology was employed to optimize both conventional extraction and ultrasound-assisted extractions. Two different models were successfully obtained (R2 = 0.8773 and R2 = 0.7436, respectively). Additionally, a further re-extraction confirmed that more agar could be extracted. Protein was also successfully co-extracted in the seaweed residues. Optimized conditions were obtained for both the extractions and the re-extraction of the two methods (CE: 6 h, 100 °C; and UAE: 1 h, 100% power). Finally, FT-IR characterization demonstrated that the extracts had a similar spectrum to the commercial agar. Compared to commercial samples, the low gel strength of the agar extracts shows that these extracts might have novel and different potential applications.

14.
Comput Struct Biotechnol J ; 19: 6050-6063, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34849208

RESUMO

The G-protein coupled receptor, GPR120, has ubiquitous expression and multifaceted roles in modulating metabolic and anti-inflammatory processes. Recent implications of its role in cancer progression have presented GPR120 as an attractive oncogenic drug target. GPR120 gene knockdown in breast cancer studies revealed a role of GPR120-induced chemoresistance in epirubicin and cisplatin-induced DNA damage in tumour cells. Higher expression and activation levels of GPR120 is also reported to promote tumour angiogenesis and cell migration in colorectal cancer. Some agonists targeting GPR120 have been reported, such as TUG891 and Compound39, but to date development of small-molecule inhibitors of GPR120 is limited. Herein, following homology modelling of the receptor a pharmacophore hypothesis was derived from 300 ns all-atomic molecular dynamics (MD) simulations on apo, TUG891-bound and Compound39-bound GPR120S (short isoform) receptor models embedded in a water solvated lipid bilayer system. We performed comparative MD analysis on protein-ligand interactions between the two agonist and apo simulations on the stability of the "ionic lock" - a Class A GPCRs characteristic of receptor activation and inactivation. The detailed analysis predicted that ligand interactions with W277 and N313 are critical to conserve the "ionic-lock" conformation (R136 of Helix 3) and prevent GPR120S receptor activation. The results led to generation of a W277 and N313 focused pharmacophore hypothesis and the screening of the ZINC15 database using ZINCPharmer through the structure-based pharmacophore. 100 ns all-atomic molecular dynamics (MD) simulations were performed on 9 small molecules identified and Cpd 9, (2-hydroxy-N-{4-[(6-hydroxy-2-methylpyrimidin-4-yl) amino] phenyl} benzamide) was predicted to be a small-molecule GPR120S antagonist. The conformational results from the collective all-atomic MD analysis provided structural information for further identification and optimisation of novel druggable inhibitors of GPR120S using this rational design approach, which could have future potential for anti-cancer drug development studies.

15.
Biomedicines ; 9(11)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34829745

RESUMO

Glioblastoma multiforme (GBM) is the most aggressive and commonly diagnosed brain cancer and is highly resistant to routine chemotherapeutic drugs. The present study involves the synthesis of Lignin-g-p (NIPAM-co-DMAEMA) gold nanogel, loaded with curcumin and piperine, to treat GBM. The ongoing study has the application potential to (1) overcome the limitations of drugs biodistribution, (2) enhance the toxicity of anticancer drugs against GBM, and (3) identify the drugs uptake pathway. Atom transfer radical polymerization was used to synthesize the Lignin-g-PNIPAM network, crosslinked with the gold nanoparticles (GNPs) to self-assemble into nanogels. The size distribution and morphological analysis confirmed that the drug-loaded gold nanogels are spherical and exist in the size of 180 nm. The single and combinatorial toxicity effects of curcumin- and piperine-loaded Lignin-g-p (NIPAM-co-DMAEMA) gold nanogels were studied against U-251 MG GBM cells. A cytotoxicity analysis displayed anticancer properties. IC50 of curcumin- and piperine-loaded gold nanogels were recorded at 30 µM and 35 µM, respectively. Immunostaining and Western blot analysis confirmed the protein expression of caspase-3 and cleaved caspase-3 in cells treated with drug-loaded nanogels. Kinetic drug release revealed 86% release of hybrid curcumin-piperine from gold nanogel after 250 min at pH 4. Atomic absorption spectroscopic analysis confirmed that the drug-loaded nanogels have better internalization or association with the cancer cells than the GNPs or nano-gels alone. Morphological studies further confirmed that the curcumin and piperine nanogels penetrate the cells via endocytic pathways and induce caspase-3-related apoptosis. The experimental evidence shows the enhanced properties of combinatorial curcumin-piperine gold nanogels (IC50: 21 µM) to overcome the limitations of conventional chemotherapeutic treatments of glioma cells.

16.
Eur J Med Chem ; 224: 113736, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34384944

RESUMO

Pyrazolopyrimidinones are fused nitrogen-containing heterocyclic systems, which act as a core scaffold in many pharmaceutically relevant compounds. Pyrazolopyrimidinones have been demonstrated to be efficient in treating several diseases, including cystic fibrosis, obesity, viral infection and cancer. In this study using glioblastoma U-251MG cell line, we tested the cytotoxic effects of 15 pyrazolopyrimidinones, synthesised via a two-step process, in combination with cold atmospheric plasma (CAP). CAP is an adjustable source of reactive oxygen and nitrogen species as well as other unique chemical and physical effects which has been successfully tested as an innovative cancer therapy in clinical trials. Significantly variable cytotoxicity was observed with IC50 values ranging from around 11 µM to negligible toxicity among tested compounds. Interestingly, two pyrazolopyrimidinones were identified that act in a prodrug fashion and display around 5-15 times enhanced reactive-species dependent cytotoxicity when combined with cold atmospheric plasma. Activation was evident for direct CAP treatment on U-251MG cells loaded with the pyrazolopyrimidinone and indirect CAP treatment of the pyrazolopyrimidinone in media before adding to cells. Our results demonstrated the potential of CAP combined with pyrazolopyrimidinones as a programmable cytotoxic therapy and provide screened scaffolds that can be used for further development of pyrazolopyrimidinone prodrug derivatives.


Assuntos
Antineoplásicos/uso terapêutico , Glioblastoma/tratamento farmacológico , Gases em Plasma/metabolismo , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Humanos , Pirazóis/farmacologia , Piridinas/farmacologia , Relação Estrutura-Atividade
17.
Trends Cancer ; 7(10): 886-890, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34426143

RESUMO

Various complex biological effects occur when ultrasonic compression waves travel through biological material. The myriad of biological outcomes instigated by ultrasound are evident when viewed through the lens of the hallmarks of cancer. Herein, we summarise the therapeutic potential of ultrasound, enhanced by microbubbles, for the treatment of cancer.


Assuntos
Microbolhas , Neoplasias , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Ondas Ultrassônicas
18.
Int J Biol Macromol ; 186: 994-1002, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34216667

RESUMO

The objective of this study was to investigate the antimicrobial and anticancer properties of a fucoidan extract and subsequent fractions isolated from the macroalgae Fucus vesiculosus. The fractions obtained (>300 kDa, <300 kDa, <100 kDa, <50 kDa and <10 kDa) could inhibit the growth of B. subtilis, E. coli, L. innocua and P. fluorescens when assayed at concentrations between 12,500 and 25,000 ppm. The bacterial growth was monitored by optical density (OD) measurements (600 nm, 24 h) at 30 °C or 37 °C, depending upon on the strain used. The extracted fractions were also tested for cytotoxicity against brain glioblastoma cancer cells using the Alamar Blue assay for 24 h, 48 h and 6 days. The >300 kDa fraction presented the lowest IC50 values (0.052% - 24 h; 0.032% - 6 days). The potential bioactivity of fucoidan as an antimicrobial and anticancer agent was demonstrated in this study. Hence, the related mechanisms of action should be explored in a near future.


Assuntos
Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Fucus/metabolismo , Glioma/tratamento farmacológico , Polissacarídeos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/crescimento & desenvolvimento , Bactérias/crescimento & desenvolvimento , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Glioma/patologia , Humanos , Microbiologia Industrial , Concentração Inibidora 50 , Listeria/efeitos dos fármacos , Listeria/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Peso Molecular , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Pseudomonas fluorescens/efeitos dos fármacos , Pseudomonas fluorescens/crescimento & desenvolvimento
19.
J Mater Chem B ; 9(32): 6326-6346, 2021 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-34304256

RESUMO

Reactive oxygen species (ROS) are generated in cellular metabolism and are essential for cellular signalling networks and physiological functions. However, the functions of ROS are 'double-edged swords' to living systems that have a fragile redox balance between ROS generation and elimination. A modest increase of ROS leads to enhanced cell proliferation, survival and benign immune responses, whereas ROS stress that overwhelms the cellular antioxidant capacity can damage nucleic acids, proteins and lipids, resulting in oncogenic mutations and cell death. ROS are therefore involved in many pathological conditions. On the other hand, ROS present selective toxicity and have been utilised against cancer and pathogens, thus also acting as a double-edged sword in the healthcare field. Injectable antioxidative hydrogels are gel precursors that form hydrogel constructs in situ upon delivery in vivo to maintain an antioxidative capacity. These hydrogels have been developed to counter ROS-induced pathological conditions, with significant advantages of biocompatibility, excellent moldability, and minimally invasive delivery. The intrinsic, readily controllable ROS-scavenging ability of the functionalised hydrogels overcomes many drawbacks of small molecule antioxidants. This review summarises the roles of ROS under pathological conditions and describes the state-of-the-art of injectable antioxidative hydrogels. A particular emphasis is also given to current ROS-producing therapeutic interventions, enabling potential application of injectable antioxidant hydrogels to prevent the adverse effects of many cancer and infection treatments.


Assuntos
Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Hidrogéis/administração & dosagem , Hidrogéis/farmacologia , Espécies Reativas de Oxigênio , Animais , Humanos , Injeções , Oxirredução , Transdução de Sinais
20.
Drug Discov Today ; 26(12): 2858-2870, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34271165

RESUMO

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumour in adults. Treatments include surgical resection, radiotherapy, and chemotherapy. Despite this, the prognosis remains poor, with an impacted quality of life during treatment coupled with brain tumour recurrence; thus, new treatments are desperately needed. In this review, we focus on recent advances in G-protein-coupled receptor (GPCR) targets. To date, the most promising targets are the chemokine, cannabinoid, and dopamine receptors, but future work should further examine the melanocortin receptor-4 (MC4R), adhesion, lysophosphatidic acid (LPA) and smoothened (Smo) receptors to initiate new drug-screening strategies and targeted delivery of safe and effective GBM therapies.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Receptores Acoplados a Proteínas G/metabolismo , Adulto , Animais , Antineoplásicos/farmacologia , Neoplasias Encefálicas/patologia , Desenvolvimento de Medicamentos , Glioblastoma/patologia , Humanos , Terapia de Alvo Molecular , Recidiva Local de Neoplasia , Prognóstico , Qualidade de Vida
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