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This paper presents an experimental investigation of nanocomposites composed of three ratios of epoxy/graphene nanoplatelets (GNPs) by weight. The 0.1, 0.2, and 0.3 wt.% specimens were carefully manufactured, and their mechanical and thermal conductivity properties were examined. The tensile strength and modulus of epoxy/GNPs were enhanced by the large surface area of graphene nanoplatelets, causing crack deflection that created new fracture fronts and friction because of the rough fracture surface. However, the compressive strength was gradually reduced as GNP loading percentages increased. This was probably due to severe plastic yielding on the epoxy, leading to catastrophic axial splitting caused by premature fractures. Furthermore, the highest thermal conductivity was 0.1283 W/m-K, representing a 20.92% improvement over neat epoxy (0.1061 W/m-K) when 0.3 wt.% GNPs were added to the epoxy. This was because of efficient heat propagation in the GNPs due to electron movement through percolative paths. The tensile failure mode in epoxy/GNP nanocomposites showed a few deflected and bifurcated rough cracks and brittle, dimple-like fractures. Contrarily, compressive failure mode in GNP-added epoxy showed plastic flexural buckling and brittle large-axial splitting. The epoxy/GNP nanocomposites were considered a damage-tolerant material.
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Nanoparticles have recently become considered as a crucial player in contemporary medicine, with therapeutic uses ranging from contrast agents in imaging to carriers for the transport of drugs and genes into a specific target. Nanoparticles have the ability to have more precise molecular interactions with the human body in order to target specific cells and tissues with minimal adverse effects and maximal therapeutic outcomes. With the least number of side effects and the greatest possible therapeutic benefit, nanoparticles can target particular cells and tissues through more precise molecular interactions with the human body. The majority of global public health problems are now treated with green synthesized silver nanoparticles (AgNPs), which substantially affect the fundamental structure of DNA and proteins and thus display their antimicrobial action. AgNPs can inhibit the proliferation of tumor cells and induce oxidative stress. By inhibiting vascular endothelial growth factor (HIF)-1, pro-inflammatory mediators generated by silver nanoparticles are reduced, mucin hypersecretion is lessened, and gene activity is subsequently regulated to prevent infections. The biogenic synthesis of silver nanoparticles (AgNPs) using various plants and their applications in antibacterial, antifungal, antioxidant, anticancer, anti-inflammatory, and antidiabetic activities have been extensively discussed in this article. Also, because only natural substances are utilized in the manufacturing process, the particles that are created naturally are coated, stabilized, and play a vital role in these biomedical actions. The characterization of AgNPs, possibility of preparing AgNPSs with different shapes using biological method and their impact on functions and toxicities, impact of size, shape and other properties on AgNPs functions and toxicity profiles, limitations, and future prospects of green-mediated AgNPs have also been reported in this study. The major goal of this study is to provide readers with a comprehensive, informed, and up-to-date summary of the various AgNPs production and characterization methods and their under-investigational antioxidant, antibacterial, and anticancer, antidiabetic, antifungal and anti-inflammatory properties. This review provides instructions and suggestions for additional studies based on AgNPs. This evaluation also pushes researchers to look into natural resources like plant parts in order to create useful nanobiotechnology.
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Canonical pyroptosis is type of programmed cell death depending on active caspase-1, and the inflammasome carries out caspase-1 activation. Here, we showed that docosahexaenoic acid (DHA) induced ovarian cancer cell deaths in caspase-1-dependent manner. DHA increased caspase-1 activity and led to interleukin-1ß secretion and gasdermin D cleavage while disulfiram inhibited DHA-induced cell death, suggesting that DHA triggered pyroptosis. Intriguingly, ASC, the molecule recruiting caspase-1 to inflammasome for activation, was dispensable for DHA-induced pyroptosis. Instead, we observed remarkable elevation in caspase-1 abundance concurrent with the activation of caspase-1 in DHA-treated cells. As ectopically overexpressing caspase-1 resulted in robust amount of active caspase-1, we reason that DHA activates caspase-1 and pyroptosis through the generation of excessive amount of caspase-1 protein. Mechanistically, DHA increased caspase-1 by specifically accelerating caspase-1 protein synthesis via the p38MAPK/Mnk1 signaling pathway. We have uncovered an unknown pyroptosis mechanism in which caspase-1-dependent pyroptosis can occur without the participation of ASC/inflammasome.
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FOXP2 encodes the forkhead transcription factor that plays a significant role in language development. Single nucleotide polymorphisms in FOXP2 have been linked to speech- language disorder, autism, cancer and schizophrenia. So, scrutinizing the functional SNPs to better understand their association in disease is an uphill task. The purpose of the current study was to identify the missense SNPs which have detrimental structural and functional effects on the FOXP2 protein. Multiple computational tools were employed to investigate the deleterious role of non-synonymous SNPs. Five variants as Y531H, L558P, R536G and R553C were found to be associated with diseases and located at the forkhead domain of the FOXP2 protein. Molecular docking analysis of FOXP2 DNA binding domain with its most common target sequence 5'-CAAATT-3' predicted that R553C and L558P mutant variants destabilize protein structure by changing protein-DNA interface interactions and disruption of hydrogen bonds that may reduce the specificity and affinity of the binding. Further experimental investigations may need to verify whether this kind of structural and functional variations dysregulate protein activities and induce formation of disease.
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Factores de Transcripción Forkhead , Polimorfismo de Nucleótido Simple , ADN/genética , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Humanos , Simulación del Acoplamiento Molecular , Dominios ProteicosRESUMEN
Federated learning methods offer secured monitor services and privacy-preserving paradigms to end-users and organisations in the Internet of Things networks such as smart healthcare systems. Federated learning has been coined to safeguard sensitive data, and its global aggregation is often based on a centralised server. This design is vulnerable to malicious attacks and could be breached by privacy attacks such as inference and free-riding, leading to inefficient training models. Besides, uploaded analysing parameters by patients can reveal private information and the threat of direct manipulation by the central server. To address these issues, we present a three-fold Federated Edge Aggregator, the so-called Edge Intelligence, a federated learning-based privacy protection framework for safeguarding Smart Healthcare Systems at the edge against such privacy attacks. We employ an iteration-based Conventional Neural Network (CNN) model and artificial noise functions to balance privacy protection and model performance. A theoretical convergence bound of Edge Intelligence on the trained federated learning model's loss function is also introduced here. We evaluate and compare the proposed framework with the recently established methods using model performance and privacy budget on popular and recent datasets: MNIST, CIFAR10, STL10, and COVID19 chest x-ray. Finally, the proposed framework achieves 90% accuracy and a high privacy rate demonstrating better performance than the baseline technique.
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COVID-19 , Privacidad , Humanos , Fenbendazol , Inteligencia , InternetRESUMEN
Greenhouse gas (GHG) emissions from agriculture sector play an important role for global warming and climate change. Thus, it is necessary to find out GHG emissions mitigation strategies from rice cultivation. The efficient management of nitrogen fertilizer using urea deep placement (UDP) and the use of the water-saving alternate wetting and drying (AWD) irrigation could mitigate greenhouse gas (GHG) emissions and reduce environmental pollution. However, there is a dearth of studies on the impacts of UDP and the integrated plant nutrient system (IPNS) which combines poultry manure and prilled urea (PU) with different irrigation regimes on GHG emissions, nitrogen use efficiency (NUE) and rice yields. We conducted field experiments during the dry seasons of 2018, 2019, and 2020 to compare the effects of four fertilizer treatments including control (no N), PU, UDP, and IPNS in combination with two irrigation systems- (AWD and continuous flooding, CF) on GHG emissions, NUE and rice yield. Fertilizer treatments had significant (p < 0.05) interaction effects with irrigation regimes on methane (CH4) and nitrous oxide (N2O) emissions. PU reduced CH4 and N2O emissions by 6% and 20% compared to IPNS treatment, respectively under AWD irrigation, but produced similar emissions under CF irrigation. Similarly, UDP reduced cumulative CH4 emissions by 9% and 15% under AWD irrigation, and 9% and 11% under CF condition compared to PU and IPNS treatments, respectively. Across the year and fertilizer treatments, AWD irrigation significantly (p < 0.05) reduced cumulative CH4 emissions and GHG intensity by 28%, and 26%, respectively without significant yield loss compared to CF condition. Although AWD irrigation increased cumulative N2O emissions by 73%, it reduced the total global warming potential by 27% compared to CF irrigation. The CH4 emission factor for AWD was lower (1.67 kg ha-1 day-1) compared to CF (2.33 kg ha-1 day-1). Across the irrigation regimes, UDP increased rice yield by 21% and N recovery efficiency by 58% compared to PU. These results suggest that both UDP and AWD irrigation might be considered as a carbon-friendly technology.
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Gases de Efecto Invernadero , Oryza , Agricultura , Fertilizantes/análisis , Gases de Efecto Invernadero/análisis , Metano/análisis , Óxido Nitroso/análisis , Suelo , Agua , Abastecimiento de AguaRESUMEN
INTRODUCTION: Shigella continues to cause significant morbidity and mortality each year, mostly in under-five children living in developing countries. We investigated the association between Shigella virulence genes and shigellosis. METHODOLOGY: We randomly selected 61 S. flexneri strains isolated from patients in Bangladesh between 2009 and 2013, and evaluated the presence of 140 MDa large-virulence-plasmid (p140), and 22 virulence genes including ipaH, ial, toxin, and T3SS-related genes. RESULTS: We found p140 in 79% (n = 48) and ipaBCD in 90% (n = 55) strains, while seven strains were missing the p140. The prevalence of ial was 89%, ipgC and ipgE was 85%, and the prevalence for the remaining genes was < 85%. During the multivariate analysis, we found that instead of sen, the Shigella enterotoxin gene set along with several other virulence genes such as ipgA, icsB, ipgB1, spa15, and mxiC, were significantly influencing multiple clinical features relevant to shigellosis, including bloody stool, mucoid stool, and rectal straining. CONCLUSIONS: We believe our model will help to determine the actual disease burden by directly looking for the genetic material in clinically suggestive patients, especially when detecting the causative organisms by traditional means is difficult.
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Disentería Bacilar , Shigella , Humanos , Disentería Bacilar/epidemiología , Disentería Bacilar/diagnóstico , Plásmidos , Shigella/genética , Shigella flexneri/genética , Virulencia/genética , Factores de Virulencia/genéticaRESUMEN
Antimicrobial resistance (AMR) is a major problem globally. The main bacterial organisms associated with urinary tract infection (UTI) associated sepsis are E. coli and Klebsiella along with Enterobacter species. These all have AMR strains known as ESBL (Extended Spectrum Beta-Lactamase), which are featured on the WHO priority pathogens list as "critical" for research. Bacteriophages (phages), as viruses that can infect and kill bacteria, could provide an effective tool to tackle these AMR strains. There is currently no "gold standard" for developing a phage cocktail. Here we describe a novel approach to develop an effective phage cocktail against a set of ESBL-producing E. coli and Klebsiella largely isolated from patients in United Kingdom hospitals. By comparing different measures of phage efficacy, we show which are the most robust, and suggest an efficient screening cascade that could be used to develop phage cocktails to target other AMR bacterial species. A target panel of 38 ESBL-producing clinical strains isolated from urine samples was collated and used to test phage efficacy. After an initial screening of 68 phages, six were identified and tested against these 38 strains to determine their clinical coverage and killing efficiency. To achieve this, we assessed four different methods to assess phage virulence across these bacterial isolates. These were the Direct Spot Test (DST), the Efficiency of Plating (EOP) assay, the planktonic killing assay (PKA) and the biofilm assay. The final ESBL cocktail of six phages could effectively kill 23/38 strains (61%), for Klebsiella 13/19 (68%) and for E. coli 10/19 (53%) based on the PKA data. The ESBL E. coli collection had six isolates from the prevalent UTI-associated ST131 sequence type, five of which were targeted effectively by the final cocktail. Of the four methods used to assess phage virulence, the data suggests that PKAs are as effective as the much more time-consuming EOPs and data for the two assays correlates well. This suggests that planktonic killing is a good proxy to determine which phages should be used in a cocktail. This assay when combined with the virulence index also allows "phage synergy" to inform cocktail design.
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α-Lipoic acid (ALA) and its reduced form dihydrolipoic acid (DHLA) are endogenous dithiol compounds with significant antioxidant properties, both of which have the potential to detoxify cells. In this study, ALA (250 µM) and DHLA (50 µM) were applied to reduce metal (As, Cd, and Pb)-induced toxicity in PC12 and Caco-2 cells as simultaneous exposure. Both significantly decreased Cd (5 µM)-, As (5 µM)-, and Pb (5 µM)-induced cell death. Subsequently, both ALA and DHLA restored cell membrane integrity and intracellular glutathione (GSH) levels, which were affected by metal-induced toxicity. In addition, DHLA protected PC12 cells from metal-induced DNA damage upon co-exposure to metals. Furthermore, ALA and DHLA upregulated the expression of survival-related proteins mTOR (mammalian target of rapamycin), Akt (protein kinase B), and Nrf2 (nuclear factor erythroid 2-related factor 2) in PC12 cells, which were previously downregulated by metal exposure. In contrast, in Caco-2 cells, upon co-exposure to metals and ALA, Nrf2 was upregulated and cleaved PARP-1 (poly (ADP-ribose) polymerase-1) was downregulated. These findings suggest that ALA and DHLA can counterbalance the toxic effects of metals. The protection of ALA or DHLA against metal toxicity may be largely due to an enhancement of antioxidant defense along with reduced glutathione level, which ultimately reduces the cellular oxidative stress.
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Ácido Tióctico , Animales , Antioxidantes , Células CACO-2 , Humanos , Estrés Oxidativo , Células PC12 , Ratas , Ácido Tióctico/análogos & derivados , Ácido Tióctico/farmacologíaRESUMEN
Glioblastoma multiforme (GBM) is a highly malignant and rapidly advancing astrocytic brain tumor in adults. Current therapy possibilities are chemotherapy, surgical resection, and radiation. The complexity of drug release through the blood-brain barrier, tumor reaction to chemotherapy, and the inherent resistance of tumor cells present challenges. New therapies are needed for individual use or combination with conventional methods for more effective treatment and improved survival for patients. GBM is difficult to treat because it grows quickly, spreads finger-shaped tentacles, and creates an irregular margin of normal tissue surrounding the tumor. Non-thermal biocompatible plasma (NBP) has recently been shown to selectively target cancer cells with minimal effects on regular cells, acting by generating reactive oxygen species (ROS) and reactive nitrogen species (RNS). We applied a soft jet plasma device with a syringe shape to U87 MG cells and astrocytes. Our results show that NBP-J significantly inhibits cell proliferation and changes morphology, induces cell cycle arrest, inhibits the survival pathway, and induces apoptosis. Our results indicate that NBP-J may be an efficient and safe clinical device for brain cancer therapy.
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Apoptosis/efectos de los fármacos , Materiales Biocompatibles/farmacología , Neoplasias Encefálicas/patología , Gases em Plasma/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Forma de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Green synthesized silver nanoparticles (Ag-NPs) have demonstrated promising effects, including cytotoxicity and anticancer potential, in different cell lines. Therefore, in our previous study, Ag-NPs were synthesized from the reduction of AgNO3 using Brassica rapa var. japonica (Bj) leaf extract as a reducing and stabilizing agent. The synthesized Ag-NPs were spherical in shape, with a size range of 15-30 nm. They had phase-centered cubic structure with strong growth inhibition potential against some bacteria. In continuation with our previous study, in the present study, we aimed to investigate the autophagy-regulated cytotoxic effect of Ag-NPs against human epithelial colorectal adenocarcinoma cells (Caco-2 cells). We found that the Bj leaf aqueous extract facilitated Brassica silver nanoparticles (Brassica Ag-NPs)-induced NF-κB mediated autophagy in Caco-2 cells. Results showed that Ag-NPs reduced cell viability of Caco-2 cells by inducing oxidative stress and DNA damage. Therefore, to understand the mechanism underlying the death-promoting activity of Ag-NPs in Caco-2 cells, western blotting was performed. Western blot analysis showed decreased expression of NFκB and increased expression of IκB, which is a sign of autophagy initiation. In addition, autophagosome formation was accelerated by the activity of p53 and light chain 3 (LC3) II. In addition, inhibition of Akt and mTOR also played a pivotal role in autophagy formation. Finally, excessive expansion of autophagy promoted apoptosis, which subsequently resulted in necrosis. These findings support a novel cell death-promoting function of autophagy by Ag-NPs in Caco-2 cells.
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Neoplasias Colorrectales , Nanopartículas del Metal , Apoptosis , Autofagia , Células CACO-2 , Neoplasias Colorrectales/tratamiento farmacológico , Humanos , FN-kappa B , Plata/farmacologíaRESUMEN
Nonthermal, biocompatible plasma (NBP) is a promising unique state of matter that is effective against a wide range of pathogenic microorganisms. This study focused on a sterilization method for bacteria that used the dielectric barrier discharge (DBD) biocompatible plasma cabinet sterilizer as an ozone generator. Reactive oxygen species play a key role in inactivation when air or other oxygen-containing gases are used. Compared with the untreated control, Escherichia coli(E. coli), Staphylococcus aureus (S. aureus), and Salmonella typhimurium (sepsis) were inhibited by approximately 99%, or were nondetectable following plasma treatment. Two kinds of plasma sterilizers containing six- or three-chamber cabinets were evaluated. There was no noticeable difference between the two configurations in the inactivation of microorganisms. Both cabinet configurations were shown to be able to reduce microbes dramatically, i.e., to the nondetectable range. Therefore, our data indicate that the biocompatible plasma cabinet sterilizer may prove to be an appropriate alternative sterilization procedure.
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Gases em Plasma/farmacología , Esterilización/instrumentación , Esterilización/métodos , Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Materiales Biocompatibles , Desinfección/instrumentación , Desinfección/métodos , Escherichia coli/efectos de los fármacos , Viabilidad Microbiana/efectos de los fármacos , Oxígeno/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Salmonella typhimurium/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacosRESUMEN
Alternate wetting and drying (AWD) irrigation in lowland rice cultivation increases water use efficiency and could reduce greenhouse gas (GHG) emissions compared to the farmers' practice of continuous flooding (CF). However, there is a dearth of studies on the impacts of water management on methane (CH4) and nitrous oxide (N2O) emissions in Bangladesh. Multi-location field experiments were conducted during the dry seasons of 2018 and 2019 to determine the baseline emissions of CH4 and N2O from rice fields and compare the emissions from AWD irrigation and CF. CH4 and N2O emissions were measured using the closed chamber technique and their concentrations were determined using a gas chromatograph. CH4 and N2O emissions varied across water management schemes and sites. AWD irrigation significantly (p < 0.05) reduced cumulative CH4 emissions (37%, average across sites) without affecting grain yields compared to CF. The CH4 emission factor for AWD was lower (1.39 kg ha-1 day-1) compared to CF (2.21 kg ha-1 day-1). Although AWD irrigation increased seasonal cumulative N2O emissions by 46%, it did not offset reduced CH4 emissions. AWD reduced the total global warming potential (GWP) by 36% compared to CF. Similarly, GHG intensity (GHGI) in AWD was 34% smaller compared to that in CF. Emissions varied across sites and the magnitudes of seasonal cumulative CH4 and N2O emissions were higher at the Gazipur site compared to the Mymensingh site. AWD, which saves irrigation water without any yield penalty, could be considered a promising strategy to mitigate GHG emissions from rice fields in Bangladesh.
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Arsenic is a recognized highly toxic contaminant, responsible for numerous human diseases and affecting many millions of people in different parts of the world. Contrarily, curcumin is a natural dietary polyphenolic compound and the main active ingredient in turmeric. Recently it has drawn great attention due to its diverse biological activities, strong antioxidant properties and therapeutic potential against many human ailments. In this study, we aimed to explore the protective effects and the regulatory role of curcumin on arsenic-induced toxicity and gain insights into biomolecular mechanism/s. Arsenic (10 µM) treatment in PC12 cells for 24 h induced cytotoxicity by decreasing cell viability and intracellular glutathione level and increasing lactate dehydrogenase activity and DNA fragmentation. In addition, arsenic caused apoptotic cell death in PC12 cells, which were confirmed from flow cytometry results. Moreover, arsenic (10 µM) treatment significantly down-regulated the inhibition factors of autophagy/apoptosis; mTOR, Akt, Nrf2, ERK1, Bcl-x, Xiap protein expressions, up-regulated the enhanced factors of autophagy/apoptosis; ULK, LC3, p53, Bax, cytochrome c, caspase 9, cleaved caspase 3 proteins and eventually caused autophagic and apoptotic cell death. However, curcumin (2.5 µM) pretreatment with arsenic (10 µM) effectively saves PC12 cells against arsenic-induced cytotoxicity through increasing cell viability, intracellular GSH level and boosting the antioxidant defense system, and limiting the LDH activity and DNA damage. Furthermore, pretreatment of curcumin with arsenic expressively alleviated arsenic-induced toxicity and cell death by reversing the expressions of proteins; mTOR, Akt, Nrf2, ERK1, Bcl-x, Xiap, ULK, LC3, p53, Bax, cytochrome c, caspase 9 and cleaved caspase 3. Our findings indicated that curcumin showed antioxidant properties through the Nrf2 antioxidant signaling pathway and alleviates arsenic-triggered toxicity in PC12 cells by regulating autophagy/apoptosis.
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Apoptosis/efectos de los fármacos , Arsénico/toxicidad , Autofagia/efectos de los fármacos , Curcumina/farmacología , Contaminantes Ambientales/toxicidad , Animales , Antioxidantes/metabolismo , Supervivencia Celular/efectos de los fármacos , Glutatión/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Células PC12 , Ratas , Transducción de Señal/efectos de los fármacosRESUMEN
Nonthermal plasma is a promising novel therapy for the alteration of biological and clinical functions of cells and tissues, including apoptosis and inhibition of tumor progression. This therapy generates reactive oxygen and nitrogen species (RONS), which play a major role in anticancer effects. Previous research has verified that plasma jets can selectively induce apoptosis in various cancer cells, suggesting that it could be a potentially effective novel therapy in combination with or as an alternative to conventional therapeutic methods. In this study, we determined the effects of nonthermal air soft plasma jets on a U87 MG brain cancer cell line, including the dose- and time-dependent effects and the physicochemical and biological correlation between the RONS cascade and p38/mitogen-activated protein kinase (MAPK) signaling pathway, which contribute to apoptosis. The results indicated that soft plasma jets efficiently inhibit cell proliferation and induce apoptosis in U87 MG cells but have minimal effects on astrocytes. These findings revealed that soft plasma jets produce a potent cytotoxic effect via the initiation of cell cycle arrest and apoptosis. The production of reactive oxygen species (ROS) in cells was tested, and an intracellular ROS scavenger, N-acetyl cysteine (NAC), was examined. Our results suggested that soft plasma jets could potentially be used as an effective approach for anticancer therapy.
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Arsenic is awfully toxic metalloid responsible for many human diseases all over the world. Contrastingly, D-pinitol is a naturally occurring bioactive dietary compound has antioxidant properties. The objective of this study is to elucidate the protective actions of D-pinitol on arsenic-induced cytotoxicity and explore its controlling role in biomolecular mechanisms in PC12 cells. Obtained results demonstrated that co-exposure of D-pinitol with arsenic increases cell viability, decreases DNA damage and protects PC12 cells from arsenic-induced cytotoxicity by increasing glutathione (GSH) level and glutathione reductase (GR). Protein expression of western blot analysis showed that co-exposure of D-pinitol and arsenic significantly inhibited arsenic-induced autophagy which further suppressed apoptosis through up-regulation of survival factors; mTOR, p-mTOR, Akt, p-Akt, NF-кB, Nrf2, ERK1, GR, Bcl-x and down-regulation of death factors; p53, Bax, cytochrome c, LC3, although arsenic regulated those factors negatively. These results of this study suggested that D-pinitol protects PC12 cells from arsenic-induced cytotoxicity.
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Arsénico/toxicidad , Inositol/análogos & derivados , Sustancias Protectoras/farmacología , Animales , Autofagia , Supervivencia Celular , Glutatión , Humanos , Inositol/farmacología , Células PC12 , RatasRESUMEN
Shigellosis, caused by Shigella boydii type 1, is understudied and underreported. For 3 years, GEMS study identified 5.4% of all Shigella as S. boydii. We showed the prevalent serotypes of S. boydii in Bangladesh and phage-based diagnosis of S. boydii type 1, a rapid and low-cost approach. Previously typed 793 clinical S. boydii strains were used for serotype distribution. Twenty-eight environmental water samples were collected for isolation of Shigella phages. Forty-eight serotypes of Shigella and other enteric bacteria were used for testing the susceptibility to phage MK-13. Electron microscopy, restriction enzyme analysis, whole genome sequencing (WGS), and annotation were performed for extensive characterization. S. boydii type 1 is the second most prevalent serotype among 20 serotypes of S. boydii in Bangladesh. We isolated a novel phage, MK-13, which specifically lyses S. boydii type 1, but doesn't lyse other 47 serotypes of Shigella or other enteric bacteria tested. The phage belongs to the Myoviridae family and distinct from other phages indicated by electron microscopy and restriction enzyme analysis, respectively. MK-13 genome consists of 158 kbp of circularly permuted double-stranded DNA with G + C content of 49.45%, and encodes 211 open reading frames including four tRNA-coding regions. The genome has 98% identity with previously reported phage, ΦSboM-AG3, reported to have a broader host range infecting most of the S. boydii and other species of Shigella tested. To our knowledge, MK-13 is the first phage reported to be used as a diagnostic marker to detect S. boydii type 1, especially in remote settings with limited laboratory infrastructure.
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Carvacrol is a monoterpenic phenol found in essential oils, is considered a safe food additive, and possesses various therapeutic properties. Numerous studies have also deciphered the protective role of carvacrol on various cytotoxicities. We clarify the effects of carvacrol on cadmium-induced apoptosis in PC12â¯cells. Carvacrol while co-exposed with cadmium for 48â¯h raised PC12â¯cell viability in comparison to only cadmium exposed group. The co-exposure increased the cellular glutathione levels and promoted the expression of glutathione reductase. The magnitude of DNA fragmentation caused by cadmium was also ameliorated by carvacrol. Flow cytometry exhibited the apoptosis rate augmented by cadmium was reduced by carvacrol. Western blotting revealed that cadmium and carvacrol co-exposure alleviated the cadmium-induced down-regulations of mammalian target of rapamycin (mTOR), protein kinase B (Akt), nuclear factor kappa-light-chain-enhancer of activated B cells (NFÐB), extracellular signal-regulated kinase-1 (ERK-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) expressions. The co-exposure also reversed action of cadmium by suppressing the cleavage of caspase 3 and reducing the cytosolic levels of cytochrome c and apoptosis inducing factor (AIF). Moreover, carvacrol upon co-exposure significantly increased the intracellular metallothionein content. In conclusion, carvacrol strongly reduced cadmium-triggered oxidative stress and caspase-dependent and caspase-independent apoptosis in PC12â¯cells.
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Apoptosis/efectos de los fármacos , Cadmio/toxicidad , Caspasa 3/metabolismo , Cimenos/farmacología , Animales , Factor Inductor de la Apoptosis/metabolismo , Supervivencia Celular/efectos de los fármacos , Citocromos c/metabolismo , Daño del ADN , Glutatión/metabolismo , Glutatión Reductasa/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Estrés Oxidativo/efectos de los fármacos , Células PC12 , RatasRESUMEN
For the last few decades, while significant improvements have been achieved in cancer therapy, this family of diseases is still considered one of the deadliest threats to human health. Thus, there is an urgent need to find novel strategies in order to tackle this vital medical issue. One of the most pivotal causes of cancer initiation is the presence of reactive oxygen species (ROS) inside the body. Interestingly, on the other hand, high doses of ROS possess the capability to damage malignant cells. Moreover, several important intracellular mechanisms occur during the production of ROS. For these reasons, inducing ROS inside the biological system by utilizing external physical or chemical methods is a promising approach to inhibit the growth of cancer cells. Beside conventional technologies, cold atmospheric plasmas are now receiving much attention as an emerging therapeutic tool for cancer treatment due to their unique biophysical behavior, including the ability to generate considerable amounts of ROS. This review summarizes the important mechanisms of ROS generated by chemical, physical, and plasma approaches. We also emphasize the biological effects and cancer inhibition capabilities of ROS.
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In order to study the effects of contaminants on human health, fish is considered as a powerful model among all available species for risk-benefit assessments. Tenualosa ilisha and Dorosoma cepedianum are two fish species of great economic importance as they are found in undeveloped, developing and developed countries. Concentrations of heavy metals lead (Pb), cadmium (Cd), chromium (Cr), arsenic (As) and mercury (Hg) were determined using validated and accredited test methods in order to assess the potential human health risk from the dietary intake of these two selected fish species. The estimated daily intake (EDI) of all the five heavy metals was measured from the consumption of the two species considering the mean fish consumption of 61 g person-1 day-1 defined for European population. The EDI indicates that no risk to people's health with respect to the EDI of Pb, Cd, Cr, As and Hg through the consumption of the two fish species. The estimation of target hazard quotient (THQ) demonstrating the non-carcinogenic risk indicates that intake of Pb, Cd, Cr and Hg through the consumption of two fish species is safe for human health, whereas, consumption of As suggests potential risk to consumers. The estimation of carcinogenic risk of Cd, Cr and As due to the consumption of two selected fish species indicates that consumers remain at risk of cancer. Thus, these fish species should not be considered safe for human consumption.