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1.
Chemosphere ; 362: 142689, 2024 Jun 26.
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.

2.
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
3.
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
4.
Free Radic Biol Med ; 222: 1-15, 2024 May 18.
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.

5.
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
6.
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
7.
J Adv Res ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38447612

RESUMO

INTRODUCTION: Melanoma is a rare but highly malignant form of skin cancer. Although recent targeted and immune-based therapies have improved survival rates by 10-15%, effective melanoma treatment remains challenging. Therefore, novel, combinatorial therapy options such as non-thermal atmospheric pressure plasma (NTP) are being investigated to inhibit and prevent chemoresistance. Although several studies have reported the apoptotic and inhibitory effects of reactive oxygen species produced by NTP in the context of melanoma, the intricate molecular network that determines the role of microRNAs (miRNAs) in regulating NTP-mediated cell death remains unexplored. OBJECTIVES: This study aimed to explore the molecular mechanisms and miRNA networks regulated by NTP-induced oxidative stress in melanoma cells. METHODS: Melanoma cells were exposed to NTP and then subjected to high-throughput miRNA sequencing to identify NTP-regulated miRNAs. Various biological processes and underlying molecular mechanisms were assessed using Alamar Blue, propidium iodide (PI) uptake, cell migration, and clonogenic assays followed by qRT-PCR and flow cytometry. RESULTS: NTP exposure for 3 min was sufficient to modulate the expression of several miRNAs, inhibiting cell growth. Persistent NTP exposure for 5 min increased differential miRNA regulation, PI uptake, and the expression of genes involved in cell cycle arrest and death. qPCR confirmed that miR-200b-3p and miR-215-5p upregulation contributed to decreased cell viability and migration. Mechanistically, inhibiting miR-200b-3p and miR-215-5p in SK-2 cells enhancedZEB1, PI3K, and AKT expression, increasing cell proliferation and viability. CONCLUSION: This study demonstrated that NTP exposure for 5 min results in the differential regulation of miRNAs related to the PI3K-AKT-ZEB1 axis and cell cycle dysregulation to facilitate melanoma suppression.

8.
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.

9.
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.

10.
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
11.
J Biomol Struct Dyn ; 42(5): 2726-2737, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37177811

RESUMO

Medicinal plants are used from prehistoric time to cure various life-threatening bacterial diseases. Acorus calamus is an important medicinal plant widely used to cure gastrointestinal, respiratory, kidney and liver disorders. The objective of the current research was to investigate the interaction of major phytoconstituents of Acorus calamus with bacterial (6VJE) and fungal (1EA1) protein targets. Protein-ligand interactions were estimated using the AutoDock software, drug likeness was predicted by using the molinspiration server and toxicity was predicted with the swissADME and protox II servers. MD simulation of phytocompounds with the best profiles was done on the GROMACS software for 100 ns. Molecular docking results showed among all the selected major phytoconstituents, that ß-cadinene showed best binding interaction in complex with bacterial (6VJE) and fungal (1EA1) protein targets with binding energy -7.66 ± 0.1 and -7.73 ± 0.15 kcal mol-1, respectively. Drug likeness and toxicity predictions showed that ß-cadinene follows all rules of drug likeness and toxicity. MD simulation study revealed that ß-cadinene fit in binding pocket of bacterial and fungal targets and found to be stable throughout the duration of the simulation. Based on the observations from this in-silico study it is being proposed that ß-cadinene, a major phytocompound of Acorus calamus, can be considered for the treatment of bacterial and fungal infections since the study shows that it might be one of the compounds that contributes majorly to the plant's biological activity. This study needs in vitro and in vivo validation.Communicated by Ramaswamy H. Sarma.


Assuntos
Acorus , Anti-Infecciosos , Simulação de Acoplamento Molecular , Anti-Infecciosos/farmacologia , Simulação por Computador , Software
12.
Chemosphere ; 350: 140997, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38128737

RESUMO

S. enterica, S. flexneri, and V. parahaemolyticus bacteria are globally recognized to cause severe diarrheal diseases, consisting of Type III Secretion System (T3SS) effectors that help in bacterial infection and virulence in host cells. This study investigates the properties of multi-electrode cylindrical DBD plasma-generated nitric oxide water (MCDBD-PG-NOW) treatment on the survival and virulence of S. enterica, S. flexneri, and V. parahaemolyticus bacteria. The Colony Forming Unit (CFU) assay, live/dead cell staining, lipid peroxidation assay, and bacteria morphological analysis showed substantial growth inhibition of bacteria. Moreover, to confirm the interaction of reactive nitrogen species (RNS) with bacterial membrane biotin switch assay, DAF-FM, and FTIR analysis were carried out, which established the formation of S-nitrosothiols in the cell membrane, intracellular accumulation of RNS, and changes in the cell composition post-PG-NOW treatment. Furthermore, the conventional culture-based method and a quantitative PCR using propidium monoazide showed minimal VBNC induction under similar condition. The efficiency of bacteria to adhere to mammalian colon cells was significantly reduced. In addition, the infection rate was also controlled by disrupting the virulent genes, leading to the collapse of the infection mechanism. This study provides insights into whether RNS generated from PG-NOW might be beneficial for preventing diarrheal infections.


Assuntos
Bactérias , Óxido Nítrico , Animais , Virulência , Bactérias/metabolismo , Sistemas de Secreção Tipo III/genética , Sistemas de Secreção Tipo III/metabolismo , Diarreia , Proteínas de Bactérias/metabolismo , Mamíferos/metabolismo
13.
Int J Mol Sci ; 24(23)2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-38068979

RESUMO

Diabetes is one of the most significant causes of death all over the world. This illness, due to abnormal blood glucose levels, leads to impaired wound healing and, as a result, foot ulcers. These ulcers cannot heal quickly in diabetic patients and may finally result in amputation. In recent years, different research has been conducted to heal diabetic foot ulcers: one of them is using cold atmospheric pressure plasma. Nowadays, cold atmospheric pressure plasma is highly regarded in medicine because of its positive effects and lack of side effects. These conditions have caused plasma to be considered a promising technology in medicine and especially diabetic wound healing because studies show that it can heal chronic wounds that are resistant to standard treatments. The positive effects of plasma are due to different reactive species, UV radiation, and electromagnetic fields. This work reviews ongoing cold atmospheric pressure plasma improvements in diabetic wound healing. It shows that plasma can be a promising tool in treating chronic wounds, including ones resulting from diabetes.


Assuntos
Diabetes Mellitus , Pé Diabético , Gases em Plasma , Humanos , Gases em Plasma/farmacologia , Gases em Plasma/uso terapêutico , Relevância Clínica , Cicatrização , Pé Diabético/tratamento farmacológico , Pressão Atmosférica , Diabetes Mellitus/tratamento farmacológico
14.
Am J Physiol Lung Cell Mol Physiol ; 325(2): L233-L243, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37366539

RESUMO

Tobacco smoking is an established cause of pulmonary disease whose contribution to interstitial lung disease (ILD) is incompletely characterized. We hypothesized that compared with nonsmokers, subjects who smoked tobacco would differ in their clinical phenotype and have greater mortality. We performed a retrospective cohort study of tobacco smoking in ILD. We evaluated demographic and clinical characteristics, time to clinically meaningful lung function decline (LFD), and mortality in patients stratified by tobacco smoking status (ever vs. never) within a tertiary center ILD registry (2006-2021) and replicated mortality outcomes across four nontertiary medical centers. Data were analyzed by two-sided t tests, Poisson generalized linear models, and Cox proportional hazard models adjusted for age, sex, forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO), ILD subtype, antifibrotic therapy, and hospital center. Of 1,163 study participants, 651 were tobacco smokers. Smokers were more likely to be older, male, have idiopathic pulmonary fibrosis (IPF), coronary artery disease, CT honeycombing and emphysema, higher FVC, and lower DLCO than nonsmokers (P < 0.01). Time to LFD in smokers was shorter (19.7 ± 20 mo vs. 24.8 ± 29 mo; P = 0.038) and survival time was decreased [10.75 (10.08-11.50) yr vs. 20 (18.67-21.25) yr; adjusted mortality HR = 1.50, 95%CI 1.17-1.92; P < 0.0001] compared with nonsmokers. Smokers had 12% greater odds of death for every additional 10 pack yr of smoking (P < 0.0001). Mortality outcomes remained consistent in the nontertiary cohort (HR = 1.51, 95%CI = 1.03-2.23; P = 0.036). Tobacco smokers with ILD have a distinct clinical phenotype strongly associated with the syndrome of combined PF and emphysema, shorter time to LFD, and decreased survival. Smoking prevention may improve ILD outcomes.NEW & NOTEWORTHY Smoking in ILD is associated with combined pulmonary fibrosis and emphysema and worse clinical outcomes.


Assuntos
Enfisema , Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Enfisema Pulmonar , Masculino , Humanos , Estudos Retrospectivos , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/etiologia , Pulmão , Enfisema Pulmonar/etiologia , Fumar Tabaco
15.
Biochim Biophys Acta Rev Cancer ; 1878(4): 188915, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37196783

RESUMO

Despite the recent advances in cancer therapy, triple-negative breast cancers (TNBCs) are the most relapsing cancer sub-type. It is partly due to their propensity to develop resistance against the available therapies. An intricate network of regulatory molecules in cellular mechanisms leads to the development of resistance in tumors. Non-coding RNAs (ncRNAs) have gained widespread attention as critical regulators of cancer hallmarks. Existing research suggests that aberrant expression of ncRNAs modulates the oncogenic or tumor suppressive signaling. This can mitigate the responsiveness of efficacious anti-tumor interventions. This review presents a systematic overview of biogenesis and down streaming molecular mechanism of the subgroups of ncRNAs. Furthermore, it explains ncRNA-based strategies and challenges to target the chemo-, radio-, and immunoresistance in TNBCs from a clinical standpoint.


Assuntos
RNA não Traduzido , Neoplasias de Mama Triplo Negativas , Humanos , RNA não Traduzido/genética , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Transdução de Sinais
16.
Microbes Infect ; 25(7): 105150, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37178787

RESUMO

Viral infection treatment is a difficult task due to its complex structure and metabolism. Additionally, viruses can alter the metabolism of host cells, mutate, and readily adjust to harsh environments. Coronavirus stimulates glycolysis, weakens mitochondrial activity, and impairs infected cells. In this study, we investigated the efficacy of 2-DG in inhibiting coronavirus-induced metabolic processes and antiviral host defense systems, which have not been explored so far. 2-Deoxy-d-glucose (2-DG), a molecule restricting substrate availability, has recently gained attention as a potential antiviral drug. The results revealed that 229E human coronavirus promoted glycolysis, producing a significant increase in the concentration of fluorescent 2-NBDG, a glucose analog, particularly in the infected host cells. The addition of 2-DG decreased its viral replication and suppressed infection-induced cell death and cytopathic effects, thereby improving the antiviral host defense response. It was also observed that administration of low doses of 2-DG inhibited glucose uptake, indicating that 2-DG consumption in virus-infected host cells was mediated by high-affinity glucose transporters, whose levels were amplified upon coronavirus infection. Our findings indicated that 2-DG could be a potential drug to improve the host defense system in coronavirus-infected cells.


Assuntos
Coronavirus , Desoxiglucose , Humanos , Desoxiglucose/farmacologia , Virulência , Glicólise , Glucose/metabolismo , Antivirais/farmacologia
17.
Free Radic Biol Med ; 201: 26-40, 2023 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-36907254

RESUMO

Cold atmospheric plasma-treated liquids (PTLs) exhibit selective toxicity toward tumor cells and are provoked by a cocktail of reactive oxygen and nitrogen species in such liquids. Compared to the gaseous phase, these reactive species are more persistent in the aqueous phase. This indirect plasma treatment method has gradually gathered interest in the discipline of plasma medicine to treat cancer. PTL's motivated effect on immunosuppressive proteins and immunogenic cell death (ICD) in solid cancer cells is still not explored. In this study, we aimed to induce immunomodulation by plasma-treated Ringer's lactate (PT-RL) and phosphate-buffered saline (PT-PBS) solutions for cancer treatment. PTLs induced minimum cytotoxicity in normal lung cells and inhibited cancer cell growth. ICD is confirmed by the enhanced expression of damage-associated molecular patterns (DAMPs). We evidenced that PTLs induce intracellular nitrogen oxide species accumulation and elevate immunogenicity in cancer cells owing to the production of pro-inflammatory cytokines, DAMPs, and reduced immunosuppressive protein CD47 expression. In addition, PTLs influenced A549 cells to elevate the organelles (mitochondria and lysosomes) in macrophages. Taken together, we have developed a therapeutic approach to potentially facilitate the selection of a suitable candidate for direct clinical applications.


Assuntos
Carcinoma , Neoplasias Pulmonares , Gases em Plasma , Humanos , Argônio/uso terapêutico , Antígeno CD47/uso terapêutico , Morte Celular Imunogênica , Neoplasias Pulmonares/tratamento farmacológico , Gases em Plasma/farmacologia , Gases em Plasma/uso terapêutico , Pulmão
18.
Sci Total Environ ; 872: 162197, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-36781138

RESUMO

Emerging bio-contaminants such as viruses have affected health and environment settings of every country. Viruses are the minuscule entities resulting in severe contagious diseases like SARS, MERS, Ebola, and avian influenza. Recent epidemic like the SARS-CoV-2, the virus has undergone mutations strengthen them and allowing to escape from the remedies. Comprehensive knowledge of viruses is essential for the development of targeted therapeutic and vaccination treatments. Animal models mimicking human biology like non-human primates, rats, mice, and rabbits offer competitive advantage to assess risk of viral infections, chemical toxins, nanoparticles, and microbes. However, their economic maintenance has always been an issue. Furthermore, the redundancy of experimental results due to aforementioned aspects is also in examine. Hence, exploration for the alternative animal models is crucial for risk assessments. The current review examines zebrafish traits and explores the possibilities to monitor emerging bio-contaminants. Additionally, a comprehensive picture of the bio contaminant and virus particle invasion and abatement mechanisms in zebrafish and human cells is presented. Moreover, a zebrafish model to investigate the emerging viruses such as coronaviridae and poxviridae has been suggested.


Assuntos
COVID-19 , Influenza Aviária , Vírus , Humanos , Animais , Camundongos , Ratos , Coelhos , Peixe-Zebra , Inativação de Vírus , SARS-CoV-2
19.
Int J Mol Sci ; 24(3)2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36768225

RESUMO

Over time, the proportion of resistant bacteria will increase. This is a major concern. Therefore, effective and biocompatible therapeutic strategies against these bacteria are urgently needed. Non-thermal plasma has been exhaustively characterized for its antibacterial activity. This study aims to investigate the inactivation efficiency and mechanisms of plasma-generated nitric oxide water (PG-NOW) on pathogenic water, air, soil, and foodborne Gram-negative and Gram-positive bacteria. Using a colony-forming unit assay, we found that PG-NOW treatment effectively inhibited the growth of bacteria. Moreover, the intracellular nitric oxide (NO) accumulation was evaluated by 4-amino-5-methylamino-2',7'-dichlorofluorescein diacetate (DAF-FM DA) staining. The reduction of viable cells unambiguously indicates the anti-microbial effect of PG-NOW. The soxR and soxS genes are associated with nitrosative stress, and oxyR regulation corresponds to oxidative stress in bacterial cells. To support the nitrosative effect mediated by PG-NOW, we have further assessed the soxRS and oxyR gene expressions after treatment. Accordingly, soxRS expression was enhanced, whereas the oxyR expression was decreased following PG-NOW treatment. The disruption of cell morphology was observed using scanning electron microscopy (SEM) analysis. In conclusion, our findings furnish evidence of an initiation point for the further progress and development of PG-NOW-based antibacterial treatments.


Assuntos
Óxido Nítrico , Estresse Nitrosativo , Óxido Nítrico/metabolismo , Estresse Oxidativo , Bactérias/metabolismo , Antibacterianos/farmacologia
20.
Bioact Mater ; 19: 569-580, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35574062

RESUMO

The ongoing pandemic caused by the novel coronavirus, SARS-CoV-2, is influencing global health. Moreover, there is a major threat of future coronaviruses affecting the entire world in a similar, or even more dreadful, manner. Therefore, effective and biocompatible therapeutic options against coronaviruses are urgently needed. To address this challenge, medical specialists require a well-informed and safe approach to treating human coronaviruses (HCoVs). Herein, an environmental friendly approach for viral inactivation, based on plasma technology, was considered. A microwave plasma system was employed for the generation of the high amount of gaseous nitric oxide to prepare nitric oxide enriched plasma-activated water (NO-PAW), the effects of which on coronaviruses, have not been reported to date. To determine these effects, alpha-HCoV-229E was used in an experimental model. We found that NO-PAW treatment effectively inhibited coronavirus infection in host lung cells, visualized by evaluating the cytopathic effect and expression level of spike proteins. Interestingly, NO-PAW showed minimal toxicity towards lung host cells, suggesting its potential for therapeutic application. Moreover, this new approach resulted in viral inactivation and greatly improved the gene levels involved in host antiviral responses. Together, our findings provide evidence of an initiation point for further progress toward the clinical development of antiviral treatments, including such coronaviruses.

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