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1.
Oral Dis ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39314203

RESUMO

OBJECTIVE: Cold atmospheric plasma (CAP) is a novel approach for cancer treatment. It can be used to treat liquids-plasma-activated media (PAM)-which are then transferred to the target as an exogenous source of reactive oxygen and nitrogen species (RONS). The present study aimed at chemically characterizing different PAM and assessing their in vitro selectivity against head and neck cancer cells (HNC). METHODS: PAM were obtained by exposing 2 and 5 mL of cell culture medium to CAP for 5, 10 and 20 min at a 6 mm working distance. Anions kinetics was evaluated by ion chromatography. Cell proliferation inhibition, apoptosis occurrence, and cell cycle modifications were assessed by MTS and flow cytometry, on human epidermal keratinocyte (HaCaT) and HNC cell lines HSC3, HSC4 and A253. RESULTS: The 2 mL conditions showed a significant reduction in cell proliferation whereas for the 5 mL the effect was milder, but the time-dependence was more evident. HaCaT were unaffected by the 5 mL PAM, indicating a selectivity for cancer cells. CONCLUSIONS: The media chemical composition modified by CAP exposure influenced cell proliferation by modulating cell cycle and inducing apoptosis in cancer cells, without affecting normal cells.

2.
J Environ Manage ; 370: 122554, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39305886

RESUMO

Synthetic dyes produced by the textile dyeing industry and released into wastewater contribute significantly to water pollution. This study explores the efficacy and versatility of a novel multi-electrode dielectric barrier discharge (MEDBD) plasma system that mainly generates ozone (O3 generator) and nitric oxide (NO generator) selectively to degrade various synthetic textile dyes, namely Methylene Blue (MB), Congo Red (CR), Methyl Orange (MO), Crystal Violet (CV), and Evans Blue (EB). Plasma achieved selective enrichment of O3 and NO by utilizing optimized plasma generation duty cycles of 15% and 100%, respectively. The proposed O3 generator plasma involves plasma-generated aqua electron impact, excited species, and reactive oxygen species notably O3, which degrades synthetic textile dyes into simple forms such as CO2, H2O, and N2. This approach achieved over 95% degradation of the above synthetic textile dyes when employing the O3 enriched plasma with 2.44 ± 0.21 W of power. Ecotoxicological evaluation, including microbial, human cell, and phytotoxicity evaluations of the O3 generator plasma for MB and CR dye-contaminated water, underscored the potential of this plasma system for environmentally friendly dye degradation. Overall, this study promotes MEDBD plasma, particularly the O3 generator, as a sustainable and efficient solution for treating synthetic dye-contaminated water across industries.

3.
Sci Total Environ ; 949: 175243, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39098420

RESUMO

Bioaccumulation of d-Limonene in environment due to the aggrandised usage of their natural sources like citrus food wastes and industrial day to day life products has raised concern to their biotoxicity to environment biotic health. Moreover, their after-usage discharge to aquatic system has enhanced the distress of posing threat and needs attention. This study entails mechanistic and molecular evaluation of in-vivo biotoxicity of d-Limonene in zebrafish embryo models. Experimental analysis excavated the controlled concentration-dependent morphological, physiological and cellular in-vivo impact of d-Limonene in zebrafish embryos through significant changes in oxidative stress, steatosis and apoptosis regulated via 6-fold and 5-fold mRNA expression change in p53 and Sod1 genes. Computational evaluation deduced the cellular mechanism of d-limonene biotoxicity as irregularities in oxidative stress, apoptosis and steatosis due of their intrinsic interaction with metabolic proteins like Zhe1a (-4.8 Kcal/mol), Sod1(-5.3 Kcal/mol), p53, caspase3 and apoa1 leading to influential change in structural and functional integrity of the metabolic proteins. The study unravelled the measured in-vivo biotoxicity of d-Limonene at cellular and molecular level to advocate the controlled usage of d-Limonene related natural and industrial product for a sustainable environmental health.


Assuntos
Apoptose , Limoneno , Estresse Oxidativo , Peixe-Zebra , Animais , Limoneno/toxicidade , Apoptose/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Fígado Gorduroso/induzido quimicamente
4.
Biomed Pharmacother ; 179: 117372, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39208668

RESUMO

Polymeric nanoparticles have emerged as promising contenders for addressing the intricate challenges encountered in brain tumor therapy due to their distinctive attributes, including adjustable size, biocompatibility, and controlled drug release kinetics. This review comprehensively delves into the latest developments in synthesizing, characterizing, and applying polymeric nanoparticles explicitly tailored for brain tumor therapy. Various synthesis methodologies, such as emulsion polymerization, nanoprecipitation, and template-assisted fabrication, are scrutinized within the context of brain tumor targeting, elucidating their advantages and limitations concerning traversing the blood-brain barrier. Furthermore, strategies pertaining to surface modification and functionalization are expounded upon to augment the stability, biocompatibility, and targeting prowess of polymeric nanoparticles amidst the intricate milieu of the brain microenvironment. Characterization techniques encompassing dynamic light scattering, transmission electron microscopy, and spectroscopic methods are scrutinized to evaluate the physicochemical attributes of polymeric nanoparticles engineered for brain tumor therapy. Moreover, a comprehensive exploration of the manifold applications of polymeric nanoparticles encompassing drug delivery, gene therapy, imaging, and combination therapies for brain tumours is undertaken. Special emphasis is placed on the encapsulation of diverse therapeutics within polymeric nanoparticles, thereby shielding them from degradation and enabling precise targeting within the brain. Additionally, recent advancements in stimuli-responsive and multifunctional polymeric nanoparticles are probed for their potential in personalized medicine and theranostics tailored for brain tumours. In essence, this review furnishes an all-encompassing overview of the recent strides made in tailoring polymeric nanoparticles for brain tumor therapy, illuminating their synthesis, characterization, and multifaceted application.


Assuntos
Neoplasias Encefálicas , Nanopartículas , Polímeros , Humanos , Polímeros/química , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Nanopartículas/química , Animais , Barreira Hematoencefálica/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Antineoplásicos/administração & dosagem , Antineoplásicos/química
5.
Mater Today Bio ; 27: 101139, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39027679

RESUMO

The prevalence of polymer usage in everyday activities has emerged as a detriment to both human life and the environment. A large number of studies describe severe impacts of micropolymers (MP) and nanopolymers (NP) on various organ systems, including the endocrine system. Additionally, plasticizers utilized as additives have been identified as endocrine-disrupting chemicals (EDCs). MP/NP, along with associated plasticizers, affect principal signalling pathways of endocrine glands such as the pituitary, thyroid, adrenal, and gonads, thereby disrupting hormone function and metabolic processes crucial for maintaining homeostasis, fertility, neural development, and fetal growth. This review delves into the sources, distribution, and effects of micropolymers, nanopolymers, and associated plasticizers acting as EDCs. Furthermore, it provides a detailed review of the mechanisms underlying endocrine disruption in relation to different types of MP/NP.

6.
Chemosphere ; 362: 142689, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38942242

RESUMO

This study proposes a novel and eco-friendly approach for wastewater treatment using plasma jet technology under bubble condition. This method allows for the controlled production of highly reactive hydroxyl radicals (OH•) while minimizing unwanted interactions with nitrogen in the air. The presence of bubbles in liquid significantly boosts the diffusion of OH• within the wastewater, leading to a two-fold increase in degradation rate compared to normal condition. The effectiveness of the treatment was confirmed through ultraviolet-visible spectroscopy, which showed a significant decrease in rhodamine B and methyl orange absorbance peaks. Raman spectroscopy further revealed structural changes in both pollutants, indicating successful degradation. Additionally, plasma characteristics like power, electron temperature, and density were monitored to gain deeper insights into the underlying mechanism. Importantly, the process minimizes the formation of harmful secondary pollutants such as ozone and nitrogen oxides. These pollutants were found under concentration of 0.14 mg m-3 which is below established safety thresholds, adhering to World Health Organization guidelines. This research demonstrates that plasma jet treatment in bubble condition not only enhances the degradation efficiency of pollutants in wastewater but also minimizes the formation of harmful byproducts. This represents a significant breakthrough in developing sustainable wastewater treatment technologies.


Assuntos
Corantes , Recuperação e Remediação Ambiental , Águas Residuárias , Poluentes Químicos da Água , Poluentes Químicos da Água/química , Águas Residuárias/química , Recuperação e Remediação Ambiental/métodos , Corantes/química , Eliminação de Resíduos Líquidos/métodos , Rodaminas/química , Radical Hidroxila/química , Gases em Plasma/química , Compostos Azo/química , Ozônio/química , Purificação da Água/métodos
7.
Biomed Pharmacother ; 176: 116921, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38870628

RESUMO

Pulp therapy has been emerged as a one of the efficient therapies in the field of endodontics. Among different types of new endodontic materials, pulpotec has been materialized as a recognized material for vital pulp therapy. However, its efficacy has been challenged due to lack of information about its cellular biocompatibility. This study evaluates the mechanistic biocompatibility of pulpotec cement with macrophage cells (RAW 264.7) at cellular and molecular level. The biocompatibility was evaluated using experimental and computational techniques like MTT assay, oxidative stress analysis and apoptosis analysis through flow cytometry and fluorescent microscopy. The results showed concentration-dependent cytotoxicity of pulpotec cement extract to RAW 264.7 cells with an LC 50 of X/10-X/20. The computational analysis depicted the molecular interaction of pulpotec cement extract components with metabolic proteins like Sod1 and p53. The study revealed the effects of Pulpotec cement's extract, showing a concentration-dependent induction of oxidative stress and apoptosis. These effects were due to influential structural and functional abnormalities in the Sod1 and p53 proteins, caused by their molecular interaction with internalized components of Pulpotec cement. The study provided a detailed view on the utility of Pulpotec in endodontic applications, highlighting its biomedical aspects.


Assuntos
Apoptose , Materiais Biocompatíveis , Macrófagos , Estresse Oxidativo , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Camundongos , Animais , Células RAW 264.7 , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Materiais Biocompatíveis/farmacologia , Teste de Materiais , Sobrevivência Celular/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Cimentos Dentários/farmacologia , Cimentos Dentários/química , Superóxido Dismutase-1/metabolismo
8.
Int J Mol Sci ; 25(12)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38928343

RESUMO

Increasing the number of resistant bacteria resistant to treatment is one of the leading causes of death worldwide. These bacteria are created in wounds and injuries and can be transferred through hospital equipment. Various attempts have been made to treat these bacteria in recent years, such as using different drugs and new sterilization methods. However, some bacteria resist drugs, and other traditional methods cannot destroy them. In the meantime, various studies have shown that cold atmospheric plasma can kill these bacteria through different mechanisms, making cold plasma a promising tool to deactivate bacteria. This new technology can be effectively used in the food industry because it has the potential to inactivate microorganisms such as spores and microbial toxins and increase the wettability and printability of polymers to pack fresh and dried food. It can also increase the shelf life of food without leaving any residue or chemical effluent. This paper investigates cold plasma's potential, advantages, and disadvantages in the food industry and sterilization.


Assuntos
Embalagem de Alimentos , Gases em Plasma , Embalagem de Alimentos/métodos , Gases em Plasma/farmacologia , Esterilização/métodos , Pressão Atmosférica , Conservação de Alimentos/métodos , Bactérias/efeitos dos fármacos
9.
Free Radic Biol Med ; 222: 1-15, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38763209

RESUMO

Non-small cell lung cancer (NSCLC), particularly lung adenocarcinoma (LUAD), significantly influences cancer-related mortality and is frequently considered by poor therapeutic responses due to genetic alterations. Cancer cells possess an inclination to develop resistance to individual treatment modalities, thus it is necessary to investigate several pathways simultaneously to obtain insights that will aid in the establishment of improved therapeutic approaches. Exploring regulated cell death (RCD) mechanisms offers promising avenues to augment immunotherapy by reshaping the tumor microenvironment (TME). Here, we investigated the prospective of microwave plasma-infused nitric oxide water (NOW) to initiate immunogenic cell death (ICD) while concurrently modulating autophagy and ferroptosis signaling in LUAD-associated A549 cells. Plasma treatment results in stable NO species nitrite/nitrate (NO2-/NO3-) in the water, altering its physicochemical properties. Analysis of ICD markers reveals increased expression of damage-associated molecular patterns (DAMPs) at both protein and mRNA levels post-NOW exposure. Intracellular reactive oxygen and nitrogen species (RONS) accumulation suggests NO-mediated mitochondrial dysfunction, triggering autophagy induction. Flow cytometry and western blotting confirm alterations in autophagy regulators Beclin 1 and SQSTM1. Furthermore, NOW treatment induces lipid peroxidation and upregulates ferroptosis-associated genes, as determined by qRT-PCR. Transmission electron microscopy (TEM) imaging reveals autophagosome formation and loss of cristae structures, corroborating the occurrence of autophagy and ferroptosis. Our findings propose that NOW may considered as inducer of ICD and the stimulation of other RCD-related proteins may enhance the anti-tumor immunogenicity.


Assuntos
Adenocarcinoma de Pulmão , Morte Celular Autofágica , Ferroptose , Neoplasias Pulmonares , Mitocôndrias , Óxido Nítrico , Humanos , Óxido Nítrico/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Morte Celular Autofágica/imunologia , Células A549 , Morte Celular Imunogênica/efeitos dos fármacos , Água/metabolismo , Água/química , Microambiente Tumoral/imunologia , Espécies Reativas de Oxigênio/metabolismo , Autofagia/imunologia
10.
J Med Virol ; 96(5): e29655, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38727091

RESUMO

Viruses can spread through contaminated aerosols and contaminated surface materials, and effective disinfection techniques are essential for virus inactivation. Nonthermal plasma-generated reactive oxygen and nitrogen species can effectively inactivate the coronavirus. We aim to interpret the coronavirus inactivation level and mechanism of surface interaction with materials with and without dielectric barrier discharge (DBD) plasma treatment. Nonthermal plasma, particularly surface-type DBD plasma, can inactivate human coronavirus 229E (HCoV-229E) on porous (paper, wood, mask) and nonporous (plastic, stainless steel, glass, Cu) materials. Virus inactivation was analyzed using a 50% tissue culture infectivity dose (TCID50) using cell line, flow cytometry, and immunofluorescence. Surfaces contaminated with HCoV-229E were treated at different time intervals (0-5 h) with and without plasma exposure (natural decay in ambient air conditions). HCoV-229E persistence conformed to the following order: plastic > cover glass > stainless steel > mask > wood > paper > Cu with and without plasma exposure. HCoV-229E was more stable in plastic, cover glass, and stainless steel in 5 h, and the viable virus titer gradually decreased from its initial log10 order of 6.892 to 1.72, 1.53, and 1.32 TCID50/mL, respectively, under plasma exposure. No virus was observed in Cu after treatment for 5 h. The use of airflow, ambient nitrogen, and argon did not promote virus inactivation. Flow cytometry and immunofluorescence analysis demonstrated a low expression level of spike protein (fluorescence intensity) during plasma treatment and in E and M genes expression compared with the virus control.


Assuntos
Coronavirus Humano 229E , Gases em Plasma , Inativação de Vírus , Humanos , Coronavirus Humano 229E/efeitos dos fármacos , Coronavirus Humano 229E/fisiologia , Inativação de Vírus/efeitos dos fármacos , Gases em Plasma/farmacologia , Linhagem Celular , Porosidade , Desinfecção/métodos , Aço Inoxidável
11.
Sci Rep ; 14(1): 10882, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740792

RESUMO

The aim of this study was to evaluate the antimicrobial efficacy of an air gas soft jet CAP for its potential use in removing oral biofilms, given that plasma-based technologies have emerged as promising methods in periodontology. Two types of biofilms were developed, one by Streptococcus mutans UA 159 bacterial strain and the other by a complex mixture of saliva microorganisms isolated from a patient with periodontitis. This latter biofilm was characterized via Next Generation Sequencing to determine the main bacterial phyla. The CAP source was applied at a distance of 6 mm for different time points. A statistically significant reduction of both CFU count and XTT was already detected after 60 s of CAP treatment. CLSM analysis supported CAP effectiveness in killing the microorganisms inside the biofilm and in reducing the thickness of the biofilm matrix. Cytotoxicity tests demonstrated the possible use of CAP without important side effects towards human gingival fibroblasts cell line. The current study showed that CAP treatment was able to significantly reduce preformed biofilms developed by both S. mutans and microorganisms isolated by a saliva sample. Further studies should be conducted on biofilms developed by additional saliva donors to support the potential of this innovative strategy to counteract oral pathogens responsible for periodontal diseases.


Assuntos
Biofilmes , Gases em Plasma , Saliva , Streptococcus mutans , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Humanos , Gases em Plasma/farmacologia , Streptococcus mutans/efeitos dos fármacos , Streptococcus mutans/fisiologia , Saliva/microbiologia , Fibroblastos/microbiologia , Fibroblastos/efeitos dos fármacos , Periodontite/microbiologia , Periodontite/terapia , Linhagem Celular , Boca/microbiologia
12.
J Hazard Mater ; 472: 134562, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38743977

RESUMO

Nosocomial infections are a serious threat and difficult to cure due to rising antibiotic resistance in pathogens and biofilms. Direct exposure to cold atmospheric plasma (CAP) has been widely employed in numerous biological research endeavors. Nonetheless, plasma-treated liquids (PTLs) formulated with physiological solutions may offer additional benefits such as enhanced portability, and biocompatibility. Additionally, CAP-infused long-lived reactive oxygen and nitrogen species (RONS) such as nitrite (NO2-), nitrate (NO3-), and hydrogen peroxide (H2O2) can synergistically induce their antibacterial activity. Herein, we investigated those argon-plasma jet-treated liquids, including Ringer's lactate (RL), phosphate-buffered saline (PBS), and physiological saline, have significant antibacterial activity against nosocomial/gastrointestinal-causing pathogens, which might be due to ROS-mediated lipid peroxidation. Combining the conventional culture-based method with propidium iodide monoazide quantitative PCR (PMAxx™-qPCR) indicated that PTLs induce a minimal viable but non-culturable (VBNC) state and moderately affect culturable counts. Specifically, the PTL exposure resulted in pathogenicity dysfunction via controlling T3SS-related effector genes of S. enterica. Overall, this study provides insights into the effectiveness of PTLs for inducing ROS-mediated damage, controlling the virulence of diarrheagenic bacteria, and modulating homeostatic genes.


Assuntos
Antibacterianos , Gases em Plasma , Gases em Plasma/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Descontaminação/métodos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Humanos , Peróxido de Hidrogênio/química
13.
Chemosphere ; 358: 142211, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38697573

RESUMO

This paper investigates the effects of argon (Ar) and that of Ar mixed with ambient air (Ar-Air) cold plasma jets (CPJs) on 4-nitrophenol (4-NP) degradation using low input power. The introduction of ambient air into the Ar-Air plasma jet enhances ionization-driven processes during high-voltage discharge by utilizing nitrogen and oxygen molecules from ambient air, resulting in increased reactive oxygen and nitrogen species (RONS) production, which synergistically interacts with argon. This substantial generation of RONS establishes Ar-Air plasma jet as an effective method for treating 4-NP contamination in deionized water (DW). Notably, the Ar-Air plasma jet treatment outperforms that of the Ar jet. It achieves a higher degradation rate of 97.2% and a maximum energy efficiency of 57.3 gkW-1h-1, following a 6-min (min) treatment with 100 mgL-1 4-NP in DW. In contrast, Ar jet treatment yielded a lower degradation rate and an energy efficiency of 75.6% and 47.8 gkW-1h-1, respectively, under identical conditions. Furthermore, the first-order rate coefficient for 4-NP degradation was measured at 0.23 min-1 for the Ar plasma jet and significantly higher at 0.56 min-1 for the Ar-Air plasma jet. Reactive oxygen species, such as hydroxyl radical and ozone, along with energy from excited species and plasma-generated electron transfers, are responsible for CPJ-assisted 4-NP breakdown. In summary, this study examines RONS production from Ar and Ar-Air plasma jets, evaluates their 4-NP removal efficacy, and investigates the biocompatibility of 4-NP that has been degraded after plasma treatment.


Assuntos
Argônio , Nitrofenóis , Gases em Plasma , Nitrofenóis/química , Argônio/química , Gases em Plasma/química , Ar , Espécies Reativas de Oxigênio/metabolismo , Poluentes Químicos da Água/toxicidade
14.
Cancer Lett ; 594: 216990, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38801886

RESUMO

Current methods of cancer therapy have demonstrated enormous potential in tumor inhibition. However, a high dosage regimen of chemotherapy results in various complications which affect the normal body cells. Tumor cells also develop resistance against the prescribed drugs in the whole treatment regimen increasing the risk of cancer relapse. Metronomic chemotherapy is a modern treatment method that involves administering drugs at low doses continuously, allowing the drug sufficient time to take its effect. This method ensures that the toxicity of the drugs is to a minimum in comparison to conventional chemotherapy. Nanoparticles have shown efficacy in delivering drugs to the tumor cells in various cancer therapies. Combining nanoparticles with metronomic chemotherapy can yield better treatment results. This combination stimulates the immune system, improving cancer cells recognition by immune cells. Evidence from clinical and pre-clinical trials supports the use of metronomic delivery for drug-loaded nanoparticles. This review focuses on the functionalization of nanoparticles for improved drug delivery and inhibition of tumor growth. It emphasizes the mechanisms of metronomic chemotherapy and its conjunction with nanotechnology. Additionally, it explores tumor progression and the current methods of chemotherapy. The challenges associated with nano-based metronomic chemotherapy are outlined, paving the way for prospects in this dynamic field.


Assuntos
Administração Metronômica , Nanopartículas , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Nanopartículas/administração & dosagem , Antineoplásicos/administração & dosagem , Animais , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos
15.
Biomed Pharmacother ; 176: 116842, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38810404

RESUMO

With advancements in nanotechnology and innovative materials, Graphene Oxide nanoparticles (GONP) have attracted lots of attention among the diverse types of nanomaterials owing to their distinctive physicochemical characteristics. However, the usage at scientific and industrial level has also raised concern to their toxicological interaction with biological system. Understanding these interactions is crucial for developing guidelines and recommendations for applications of GONP in various sectors, like biomedicine and environmental technologies. This review offers crucial insights and an in-depth analysis to the biological processes associated with GONP immunotoxicity with multiple cell lines including human whole blood cultures, dendritic cells, macrophages, and multiple cancer cell lines. The complicated interactions between graphene oxide nanoparticles and the immune system, are highlighted in this work, which reveals a range of immunotoxic consequences like inflammation, immunosuppression, immunostimulation, hypersensitivity, autoimmunity, and cellular malfunction. Moreover, the immunotoxic effects are also highlighted with respect to in vivo models like mice and zebrafish, insighting GO Nanoparticles' cytotoxicity. The study provides invaluable review for researchers, policymakers, and industrialist to understand and exploit the beneficial applications of GONP with a controlled measure to human health and the environment.


Assuntos
Grafite , Grafite/toxicidade , Grafite/química , Humanos , Animais , Nanopartículas , Sistema Imunitário/efeitos dos fármacos
16.
Int J Biol Macromol ; 270(Pt 1): 132030, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38704069

RESUMO

The proviral integration for the Moloney murine leukemia virus (PIM) kinases, belonging to serine/threonine kinase family, have been found to be overexpressed in various types of cancers, such as prostate, breast, colon, endometrial, gastric, and pancreatic cancer. The three isoforms PIM kinases i.e., PIM1, PIM2, and PIM3 share a high degree of sequence and structural similarity and phosphorylate substrates controlling tumorigenic phenotypes like proliferation and cell survival. Targeting short-lived PIM kinases presents an intriguing strategy as in vivo knock-down studies result in non-lethal phenotypes, indicating that clinical inhibition of PIM might have fewer adverse effects. The ATP binding site (hinge region) possesses distinctive attributes, which led to the development of novel small molecule scaffolds that target either one or all three PIM isoforms. Machine learning and structure-based approaches have been at the forefront of developing novel and effective chemical therapeutics against PIM in preclinical and clinical settings, and none have yet received approval for cancer treatment. The stability of PIM isoforms is maintained by PIM kinase activity, which leads to resistance against PIM inhibitors and chemotherapy; thus, to overcome such effects, PIM proteolysis targeting chimeras (PROTACs) are now being developed that specifically degrade PIM proteins. In this review, we recapitulate an overview of the oncogenic functions of PIM kinases, their structure, function, and crucial signaling network in different types of cancer, and the potential of pharmacological small-molecule inhibitors. Further, our comprehensive review also provides valuable insights for developing novel antitumor drugs that specifically target PIM kinases in the future. In conclusion, we provide insights into the benefits of degrading PIM kinases as opposed to blocking their catalytic activity to address the oncogenic potential of PIM kinases.


Assuntos
Antineoplásicos , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas c-pim-1 , Transdução de Sinais , Animais , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , Proteínas Proto-Oncogênicas c-pim-1/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-pim-1/química , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade
17.
Cancer Metastasis Rev ; 43(3): 959-975, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38451384

RESUMO

Tumor suppressor genes and proto-oncogenes comprise most of the complex genomic landscape associated with cancer, with a minimal number of genes exhibiting dual-context-dependent functions. The transcription factor cellular promoter 2 (TFCP2), a pivotal transcription factor encoded by the alpha globin transcription factor CP2 gene, is a constituent of the TFCP2/grainyhead family of transcription factors. While grainyhead members have been extensively studied for their crucial roles in developmental processes, embryogenesis, and multiple cancers, the TFCP2 subfamily has been relatively less explored. The molecular mechanisms underlying TFCP2's involvement in carcinogenesis are still unclear even though it is a desirable target for cancer treatment and a therapeutic marker. This comprehensive literature review summarizes the molecular functions of TFCP2, emphasizing its involvement in cancer pathophysiology, particularly in the epithelial-mesenchymal transition and metastasis. It highlights TFCP2's critical function as a regulatory target and explores its potential as a prognostic marker for survival and inflammation in carcinomas. Its ambiguous association with carcinomas underlines the urgent need for an in-depth understanding to facilitate the development of more efficacious targeted therapeutic modality and diagnostic tools. This study aims to elucidate the multifaceted effects of TFCP2 regulation, through a comprehensive integration of the existing knowledge in cancer therapeutics. Furthermore, the clinical relevance and the inherent challenges encountered in investigating its intricate role in cancer pathogenesis have been discussed in this review.


Assuntos
Neoplasias , Humanos , Neoplasias/genética , Neoplasias/patologia , Neoplasias/terapia , Neoplasias/metabolismo , Animais , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo
18.
Front Pharmacol ; 15: 1345340, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455958

RESUMO

This study assessed the medicinal properties of Euphorbia resinifera O. Berg (E. resinifera) and Euphorbia officinarum subsp echinus (Hook.f. and Coss.) Vindt (Euphorbia echinus, known for their pharmaceutical benefits. Extracts from their flowers, stems, propolis, and honey were examined for phenolic content, antioxidant, anti-inflammatory, and antibacterial activities. Total phenolic content (TPC), total flavonoid content (TFC), and total condensed tannin (TCC) were determined using specific methods. Antioxidant potential was assessed through various tests including DPPH, FRAP, ABTS, and Total antioxidant capacity. Anti-inflammatory effects were evaluated using phenol-induced ear edema in rats, while antibacterial activity was measured against Gram-positive (Staphylococcus aureus ATCC 6538) and Gram-negative (E. coli ATCC 10536) bacteria. Among the extracts, the aqueous propolis extract of E. resinifera demonstrated exceptional antioxidant capabilities, with low IC50 values for DPPH (0.07 ± 0.00 mg/mL) and ABTS (0.13 ± 0.00 mg/mL), as well as high TAC (176.72 ± 0.18 mg AA/mg extract) and FRAP (86.45 ± 1.45 mg AA/mg extract) values. Furthermore, the anti-inflammatory effect of E. resinifera propolis extracts surpassed that of indomethacin, yielding edema percentages of 3.92% and 11.33% for the aqueous and ethanolic extracts, respectively. Microbiological results indicated that the aqueous extract of E. resinifera flower exhibited the most potent inhibitory action against S. aureus, with an inhibition zone diameter (IZD) of 21.0 ± 0.00 mm and a minimum inhibitory concentration (MIC) of 3.125 mg/mL. Additionally, only E. resinifera honey displayed the ability to inhibit E. coli growth, with an inhibition zone diameter of 09.30 ± 0.03 mm and a MIC of 0.0433 mg/mL.

19.
Environ Pollut ; 347: 123700, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38452839

RESUMO

Emerging bio-contaminants (airborne viruses) exploits and manipulate host (human) metabolism to produce new viral particles, evading the host's immune defences and leading to infections. Non-thermal plasma, operating at atmospheric pressure and ambient temperature, is explored for virus inactivation, generating RONS that interact and denatures viral proteins. However, various factors affecting virus survival influence the efficacy of non-thermal plasma. Glucose analogue 2-DG, a metabolic modifier used in this study, disrupts the glycolysis pathway viruses rely on, creating an unfavourable environment for replication. Here, airborne HCoV-229E bio-contaminant was treated with plasma for inactivation, and the presence of RONS was analysed. Metabolically altered lung cells were subsequently exposed to the treated airborne viruses. Cytopathic effect, spike protein, and cell death were evaluated via flow cytometry and confocal microscopy, and CPRRs mediated antiviral gene expression was evaluated using PCR. Gas plasma-treated viruses led to reduced virus proliferation in unaltered lung cells, although few virus particles survived the exposure, as confirmed by biological assessment (cytopathic effects and live/dead staining). A combination approach of gas plasma-treated viruses and altered lung cells displayed drastic virus reduction compared to the control group, established through confocal microscopy and flow cytometry. Furthermore, altered lung cell enhances gene transcription responsible for innate immunity when exposed to the gas plasma-treated virus, thereby impeding airborne virus propagation. This study demonstrates the significance of a surface air gas plasma and metabolic alteration approach in enhancing genes targeted towards antiviral innate immunity and tackling outbreaks of emerging bio-contaminants of concerns (airborne viruses).


Assuntos
Coronavirus Humano 229E , Humanos , Coronavirus Humano 229E/genética , Inativação de Vírus , Pulmão , Imunidade Inata , Antivirais
20.
Biomed Pharmacother ; 171: 116160, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38237351

RESUMO

The aggrandised advancement in utility of advanced day-to-day materials and nanomaterials has raised serious concern on their biocompatibility with human and other biotic members. In last few decades, understanding of toxicity of these materials has been given the centre stage of research using many in vitro and in vivo models. Zebrafish (Danio rerio), a freshwater fish and a member of the minnow family has garnered much attention due to its distinct features, which make it an important and frequently used animal model in various fields of embryology and toxicological studies. Given that fertilization and development of zebrafish eggs take place externally, they serve as an excellent model organism for studying early developmental stages. Moreover, zebrafish possess a comparable genetic composition to humans and share almost 70% of their genes with mammals. This particular model organism has become increasingly popular, especially for developmental research. Moreover, it serves as a link between in vitro studies and in vivo analysis in mammals. It is an appealing choice for vertebrate research, when employing high-throughput methods, due to their small size, swift development, and relatively affordable laboratory setup. This small vertebrate has enhanced comprehension of pathobiology and drug toxicity. This review emphasizes on the recent developments in toxicity screening and assays, and the new insights gained about the toxicity of drugs through these assays. Specifically, the cardio, neural, and, hepatic toxicology studies inferred by applications of nanoparticles have been highlighted.


Assuntos
Nanoestruturas , Peixe-Zebra , Animais , Humanos , Modelos Animais , Fígado , Mamíferos
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