RESUMO
Here, we designed a ratiometric luminescent nanoprobe based on lanthanide-doped upconversion nanoparticles-CuMnO2 nanoassemblies for rapid and sensitive detection of reactive oxygen species (ROS) levels in living cells and mouse. CuMnO2 nanosheets exhibit a wide absorption range of 300-700 nm, overlapping with the visible-light emission of upconversion nanoparticles (UCNPs), resulting in a significant upconversion luminescence quenching. In an acidic environment, H2O2 can promote the redox reaction of CuMnO2, leading to its dissociation from the surface of UCNPs and the restoration of upconversion luminescence. The variation in luminescence intensity ratio (UCL475/UCL450) were monitored to detect ROS levels. The H2O2 nanoprobe exhibited a linear response in the range of 0.314-10 µM with a detection limit of 11.3 nM. The biological tests proved the excellent biocompatibility and low toxicity of obtained UCNPs-CuMnO2 nanoassemblies. This ratiometric luminescent nanoprobe was successfully applied for the detection of exogenous and endogenous ROS in live cells as well as in vivo ROS quantitation. The dual transition metal ions endow this probe efficient catalytic decomposition capabilities, and this sensing strategy broadens the application of UCNPs-based nanomaterials in the field of biological analysis and diagnosis.
Assuntos
Nanopartículas , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/análise , Nanopartículas/química , Animais , Camundongos , Humanos , Raios Infravermelhos , Imagem Óptica , Tamanho da Partícula , Propriedades de Superfície , Elementos da Série dos Lantanídeos/química , Peróxido de Hidrogênio/análiseRESUMO
The accumulation of photosensitizers (PSs) in lesion sites but not in other organs is an important challenge for efficient image guiding in photodynamic therapy. Cancer cells are known to express a significant number of albumin-binding proteins that take up albumin as a nutrient source. Here, we converted albumin to a novel BODIPY-like PS by generating a tetrahedral boron environment via a flick reaction. The formed albumin PS has almost the same 3-dimensional structural feature as free albumin because binding occurs at Sudlow Site 1, which is located in the interior space of albumin. An i.v. injection experiment in tumor-bearing mice demonstrated that the human serum albumin PS effectively accumulated in cancer tissue and, more surprisingly, albumin PS accumulated much more in the cancer tissue than in the liver and kidneys. The albumin PS was effective at killing tumor cells through the generation of reactive oxygen species under light irradiation. The crystal structure of the albumin PS was fully elucidated by X-ray crystallography; thus, further tuning of the structure will lead to novel physicochemical properties of the albumin PS, suggesting its potential in biological and clinical applications.
Assuntos
Compostos de Boro , Fotoquimioterapia , Fármacos Fotossensibilizantes , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Animais , Compostos de Boro/química , Humanos , Camundongos , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismo , Camundongos Nus , Albuminas/química , Albuminas/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismoRESUMO
Accurate and early detection of atherosclerosis (AS) is imperative for their effective treatment. However, fluorescence probes for efficient diagnosis of AS often encounter insufficient deep tissue penetration, which hinders the reliable assessment of plaque vulnerability. In this work, a reactive oxygen species (ROS) activated near-infrared (NIR) fluorescence and photoacoustic (FL/PA) dual model probe TPA-QO-B is developed by conjugating two chromophores (TPA-QI and O-OH) and ROS-specific group phenylboronic acid ester. The incorporation of ROS-specific group not only induces blue shift in absorbance, but also inhibits the ICT process of TPA-QO-OH, resulting an ignorable initial FL/PA signal. ROS triggers the convertion of TPA-QO-B to TPA-QO-OH, resulting in the concurrent amplification of FL/PA signal. The exceptional selectivity of TPA-QO-B towards ROS makes it effectively distinguish AS mice from the healthy. The NIR emission can achieve a tissue penetration imaging depth of 0.3 cm. Moreover, its PA775 signal possesses the capability to penetrate tissues up to a thickness of 0.8 cm, ensuring deep in vivo imaging of AS model mice in early stage. The ROS-triggered FL/PA dual signal amplification strategy improves the accuracy and addresses the deep tissue penetration problem simultaneously, providing a promising tool for in vivo tracking biomarkers in life science and preclinical applications.
Assuntos
Corantes Fluorescentes , Técnicas Fotoacústicas , Placa Aterosclerótica , Espécies Reativas de Oxigênio , Animais , Espécies Reativas de Oxigênio/metabolismo , Técnicas Fotoacústicas/métodos , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/metabolismo , Corantes Fluorescentes/química , Camundongos , Imagem Óptica/métodos , Camundongos Endogâmicos C57BL , Humanos , MasculinoRESUMO
Oxygen activation leading to the generation of reactive oxygen species (ROS) is essential for photocatalytic environmental remediation. The limited efficiency of O2 adsorption and reductive activation significantly limits the production of ROS when employing C3N4 for the degradation of emerging pollutants. Doping with metal single atoms may lead to unsatisfactory efficiency, due to the recombination of photogenerated electron-hole pairs. Here, Mn and S single atoms were introduced into C3N4, resulting in the excellent photocatalytic performances. Mn/S-C3N4 achieved 100% removal of bisphenol A, with a rate constant 11 times that of pristine C3N4. According to the experimental results and theoretical simulations, S-atoms restrict holes, facilitating the photo-generated carriers' separation. Single-atom Mn acts as the O2 adsorption site, enhancing the adsorption and activation of O2, resulting the generation of ROS. This study presents a novel approach for developing highly effective photocatalysts that follows a new mechanism to eliminate organic pollutants from water.
Assuntos
Oxigênio , Poluentes Químicos da Água , Poluentes Químicos da Água/química , Oxigênio/química , Catálise , Manganês/química , Compostos Benzidrílicos/química , Nitrilas/química , Adsorção , Espécies Reativas de Oxigênio , Recuperação e Remediação Ambiental/métodos , Fenóis/químicaRESUMO
Osteomyelitis is an osseous infectious disease that primarily affects children and the elderly with high morbidity and recurrence. The conventional treatments of osteomyelitis contain long-term and high-dose systemic antibiotics with debridements, which are not effective and lead to antibiotic resistance with serious side/adverse effects in many cases. Hence, developing novel antibiotic-free interventions against osteomyelitis (especially antibiotic-resistant bacterial infection) is urgent and anticipated. Here, a bone mesenchymal stem cell membrane-constructed nanocell (CFE@CM) was fabricated against osteomyelitis with the characteristics of acid-responsiveness, hydrogen peroxide self-supplying, enhanced chemodynamic therapeutic efficacy, bone marrow targeting and cuproptosis induction. Notably, mRNA sequencing was applied to unveil the underlying biological mechanisms and found that the biological processes related to copper ion binding, oxidative phosphorylation, peptide biosynthesis and metabolism, etc., were disturbed by CFE@CM in bacteria. This work provided an innovative antibiotic-free strategy against osteomyelitis through copper-enhanced Fenton reaction and distinct cuproptosis, promising to complement the current insufficient therapeutic regimen in clinic.
Assuntos
Cobre , Osteomielite , Osteomielite/tratamento farmacológico , Animais , Cobre/química , Cobre/farmacologia , Concentração de Íons de Hidrogênio , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Camundongos , Peróxido de Hidrogênio/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , Humanos , Staphylococcus aureus/efeitos dos fármacosRESUMO
Fine particulate matter (PM2.5) is associated with numerous adverse health effects, including pulmonary and cardiovascular diseases and premature death. Significant contributors to ambient PM2.5 include combustion particles and secondary organic aerosols (SOA). Combustion particles enter the atmosphere and undergo an aging process that changes their shape and composition, but there is limited study on the health effects of combustion particle aging and interactions with SOA. This study aimed to understand how biological responses to combustion particles would be affected by atmospheric aging and interaction with anthropogenic SOA. Fresh combustion particles underwent photochemical aging in a potential aerosol mass (PAM) oxidation flow reactor and interacted with SOA produced by the oxidation of toluene vapor in the PAM reactor. Photochemical aging and SOA interactions lead to significant changes in the PAH content and oxidative potential of the particle. Photochemical aging and SOA interactions also affected the biological responses, such as the inflammatory response and CYP1A1 induction of the particles in monoculture and coculture cells. These findings highlight the significance of photochemical aging and SOA interactions on the composition and cellular responses of combustion particles.
RESUMO
Iron-based chemodynamic therapy (CDT) exhibits commendable biocompatibility and selectivity, but its efficacy is constrained by the intracellular pH of tumors. To overcome this obstacle, we constructed a silica delivery platform loaded with autophagy-inducing reagents (rapamycin, RAPA) and iron-based Fenton reagents (Fe3O4). This platform was utilized to explore a novel strategy that leverages autophagy to decrease tumor acidity, consequently boosting the effectiveness of CDT. Both in vitro and in vivo experiments revealed that RAPA prompted the generation of acidic organelles (e.g., autophagic vacuoles and autophagosomes), effectively changing the intracellular pH in the tumor microenvironment. Furthermore, RAPA-induced tumor acidification significantly amplified the efficacy of Fe3O4-based Fenton reactions, consequently increasing the effectiveness of Fe3O4-based CDT. This innovative approach, which leverages the interplay between autophagy induction and iron-based CDT, shows promise in overcoming the limitations posed by tumor pH, thus offering a more efficient approach to tumor treatments.
Assuntos
Ferro , Concentração de Íons de Hidrogênio , Humanos , Animais , Ferro/química , Camundongos , Morte Celular Autofágica/efeitos dos fármacos , Sirolimo/farmacologia , Sirolimo/química , Microambiente Tumoral/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Propriedades de Superfície , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Autofagia/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Proliferação de Células/efeitos dos fármacosRESUMO
The clinical translation of the anticancer drug ß-lapachone (LAP) has been limited by the narrow therapeutic window. Stimuli-responsive anticancer drug delivery systems have gained tremendous attention in recent years to alleviate adverse effects and enhance therapeutic efficacy. Here, we report a dual pH- and enzyme-responsive nanocarrier to address the above issue of LAP. In detail, the epigallocatechin gallate (EGCG) and ferric ions were employed to engineer nanoscale ferric ion-polyphenol complexes where LAP was physically encapsulated therein. The coordination bond between Fe3+ and the catechol moiety of EGCG was sensitive to the low pH, enabling the triggered cargo release in the acidic endosomes/lysosomes. Afterward, the released LAP was activated by the overexpressed NAD(P)H: quinone oxidoreductase 1 (NQO1) and ferroptosis suppressor protein 1 (FSP1) in the tumor cells, followed by the generation of reactive oxygen species (ROS), and the induction of oxidative stress and apoptotic cell death. Meanwhile, EGCG could upregulate gasdermin E (GSDME), and ferric ions were involved in the Fenton reaction. Hence, EGCG and ferric ions could sensitize the toxicity of LAP through the induction of multiple cell death pathways (e.g., pyroptosis, ferroptosis, apoptosis, and necroptosis). The current work enlarged the LAP's therapeutic window via controlled cargo release and vehicle sensitization.
Assuntos
Naftoquinonas , Naftoquinonas/química , Naftoquinonas/farmacologia , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Espécies Reativas de Oxigênio/metabolismo , Catequina/análogos & derivados , Catequina/química , Catequina/farmacologia , NAD(P)H Desidrogenase (Quinona)/metabolismo , Concentração de Íons de Hidrogênio , Nanomedicina , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Tamanho da Partícula , Sobrevivência Celular/efeitos dos fármacosRESUMO
The construction of semiconductor heterojunction is an effective way for charge separation in photocatalytic degradation of pollutants. In this study, a novel MoS2@MoO3/(Cu+/g-C3N4) ternary composites (MMCCN) was prepared via a simple calcination method. The as-prepared composites exhibited exceptional performance in activating peroxymonosulfate (PMS) for the degradation of rhodamine B (RhB). The activity testing results indicated that 99.41 % of RhB (10 mg·L-1, 10 mL) was effectively removed by the synergistic effect of composites photocatalyst (0.1 g·L-1) and PMS (0.1 g·L-1) under visible light irradiation for 40 min. Its reaction rate constant exceeded that of Cu+/g-C3N4, MoO3 and MoS2 by a factor of 3.56, 17.30 and 11.73 times, respectively. The crystal structure, band gap and density of states (DOS) of the semiconductors were calculated according to the density functional theory (DFT). Free radical trapping tests and electron spin resonance spectroscopy validated that 1O2, O2- and h+ are primary reactive species participating in the decomposition of RhB. The ternary composites demonstrated good stability and maintained excellent degradation efficiency even across four reaction cycles. Furthermore, the activation mechanism and the intermediates produced during the decomposition course of RhB by MMCCN/PMS/vis system were analyzed and elucidated. A double S-scheme heterojunctions was responsible for efficient separation of photo-induced electron-hole pairs. This work presents a novel method in the construction of double S-scheme heterojunctions for PMS activation which is expected to find wide applications in wastewater treatment and environmental remediation.
RESUMO
Wood-decaying white rot fungi live in changing environmental conditions and may switch from aerobic to fermentative metabolism under oxygen depletion. Decomposition of wood and lignocellulose by fungi is dependent on enzymatic and oxidative biochemistry including generation of reactive oxygen species. In this study, we subjected semi-solid wood-substrate cultures of the white rot fungus Phlebia radiata to oxidative stress by addition of hydrogen peroxide under aerobic and anaerobic cultivation conditions. Wood decomposition and fungal metabolism were followed by analysis of extracellular organic compounds, mycelial growth, and laccase activity. Under both atmospheric conditions, accumulation of bioactive aromatic compounds from birch wood occurred into the culture supernatants after hydrogen peroxide treatment. The supernatants inhibited both fungal growth and laccase activity. However, the fungus recovered from the oxidative stress quickly in a few days, especially when cultivated under regular aerobic conditions. With repeated hydrogen peroxide treatments, laccase suppressive-recovery effect was observed. Culture supernatants demonstrated antioxidant and antimicrobial effects, in concert with emergence of chlorinated birch-derived organic compounds. Bioactivities in the cultures disappeared in the same pace as the chlorinated compounds were transformed and de-chlorinated by the fungus. Our results indicate tolerance of white rot fungi against excessive oxidative stress and wood-derived, growth-inhibiting and harmful agents.
RESUMO
Porcine oocytes undergo in vitro maturation (IVM) for 42-44 h. During this period, most oocytes proceed to metaphase and then to pro-metaphase if the nucleus has sufficiently matured. Forty-four hours is sufficient for oocyte nuclear maturation but not for full maturation of the oocyte cytoplasm. This study investigated the influences of extension of the IVM duration with rapamycin treatment on molecular maturation factors. The phospho-p44/42 mitogen-activated protein kinase (MAPK) level was enhanced in comparison with the total p44/42 MAPK level after 52 h of IVM. Oocytes were treated with and without 10 µM rapamycin (10 R and 0 R, respectively) and examined after 52 h of IVM, whereas control oocytes were examined after 44 h of IVM. Phospho-p44/42 MAPK activity was upregulated the 10 R and 0 R oocytes than in control oocytes. The expression levels of maternal genes were highest in 10 R oocytes and were higher in 0 R oocytes than in control oocytes. Reactive oxygen species (ROS) activity was dramatically increased in 0 R oocytes but was similar in 10 R and control oocytes. The 10 R group exhibited an increased embryo development rate, a higher total cell number per blastocyst, and decreased DNA fragmentation. The mRNA level of development-related (POU5F1 and NANOG) mRNA, oocyte-apoptotic (BCL2L1) genes were highest in 10 R blastocysts. These results suggest that prolonged IVM duration with rapamycin treatment represses ROS production and increases expression of molecular maturation factors. Therefore, this is a good strategy to enhance the developmental capacity in porcine oocytes.
RESUMO
We report the synthesis, characterisation, and anti-breast cancer stem cell (CSC) properties of two copper(II)-terpyridine complexes with bidentate salicylaldehyde moieties (2-hydroxybenzaldehyde for 1 and 2-hydroxy-1-naphthaldehyde for 2). The copper(II)-terpyridine complexes 1 and 2 are stable in biologically relevant aqueous solutions and display micromolar potency towards breast CSCs. The most effective complex 1 is 5-fold and 6.6-fold more potent towards breast CSCs than salinomycin and cisplatin, respectively. The copper(II)-terpyridine complexes 1 and 2 also decrease the formation and viability of three-dimensionally cultured mammospheres within the micromolar range. Notably complex 1 is up to 7-fold more potent towards mammospheres than salinomycin or cisplatin. Mechanistic studies suggest that the copper(II)-terpyridine complexes 1 and 2 are able to readily enter breast CSCs, elevate intracellular reactive oxygen species levels, induce DNA damage (presumably by oxidative DNA cleavage), and evoke apoptosis that is independent of caspases. This study shows that the copper(II)-terpyridine motif is a useful building block for the design of anti-breast CSC agents and reinforces the therapeutic potential of copper coordination complexes.
RESUMO
The valorization of toluene offers a dual solution by addressing its environmental impact while also facilitating the synthesis of a diverse array of valuable fine chemicals and pharmaceutical intermediates, thus ensuring both ecological sustainability and economic viability. We report herein a synergistic approach that harmonizes hydrogen atom transfer (HAT) process with the generation of reactive oxygen species (ROS) under mild condition and low catalyst loading, which enables the efficient synthesis of a broad spectrum of esteemed benzoic acid derivatives and aryl ketones through the photocatalytic oxidation of toluene derivatives. Mechanistic elucidation reveals that the HAT reagent anthraquinone has both the capabilities to abstract hydrogen atoms and the ability to generate singlet oxygen 1O2 during energy transfer with triplet oxygen 3O2, and the combination of these two potencies significantly improves the catalytic efficiency of the reaction. This study not only introduces the amalgamation of HAT with ROS generation but also delineates a systematic approach for the selection of HAT reagents with energy transfer proficiency for ROS generation in catalytic oxidation reactions.
RESUMO
Bacterial infections or their biofilms in diabetic foot ulcer (DFU) are a key cause of drug-resistant wounds and amputations. Cold atmospheric plasma (CAP) is well documented for its antibacterial effect and promoting wound healing. In the current study, we built an argon- based, custom CAP device and investigated its potential in eliminating laboratory and clinical bacterial strains derived from DFU. The CAP device performed as expected with generation of hydroxyl, reactive nitrogen species, and argon species as determined by optical emission spectroscopy. A dose-dependent increase in oxidation reduction potential (ORP) and nitrites in the liquid phase was observed. The CAP treatment eliminated both gram-positive (Staphylococcus aureus, Entrococcus faecalis) and negative bacteria (Pseudomonas aeruginosa, Proteus mirabilis) laboratory strains. Clinical samples collected from DFU patients exhibited a significant decrease in both types of bacteria, with grampositive strains showing higher susceptibility to the CAP treatment in an ex vivo setting. Moreover, exposure to CAP of polymicrobial biofilms from DFU led to a notable disruption in biofilm and an increase in free bacterial DNA. The duration of CAP exposure used in the current study did not induce DNA damage in peripheral blood lymphocytes. These results suggest that CAP could serve as an excellent tool in treating patients with DFUs.
RESUMO
Myocardial ischemia-reperfusion injury (MIRI) is a significant factor in the development of cardiac dysfunction following a myocardial infarction. Ferroptosis, a type of regulated cell death driven by iron and marked by lipid peroxidation, has garnered growing interest for its crucial involvement in the pathogenesis of MIRI.This review comprehensively examines the mechanisms of ferroptosis, focusing on its regulation through iron metabolism, lipid peroxidation, VDAC signaling, and antioxidant system dysregulation. We also compare ferroptosis with other forms of cell death to highlight its distinct characteristics. Furthermore, the involvement of ferroptosis in MIRI is examined with a focus on recent discoveries concerning ROS generation, mitochondrial impairment, autophagic processes, ER stress, and non-coding RNA regulation. Lastly, emerging therapeutic strategies that inhibit ferroptosis to mitigate MIRI are reviewed, providing new insights into potential clinical applications.
RESUMO
Introduction: Cardiac hypertrophy is a compensatory stress response produced by a variety of factors, and pathologic hypertrophy can lead to irreversible, severe cardiac disease. Glycosphingolipids (GSLs) are vital constituents of cells, and changes in their content and composition are important factors causing mitochondrial dysfunction in diabetic cardiomyopathy; however, the relationship between GSLs expression and cardiac hypertrophy and specific mechanisms associated with it are not clear. Methods: Here, using male C57BL/6 mice, we performed aortic arch reduction surgery to establish an animal model of pressure overload cardiac hypertrophy. In addition, phenylephrine was used in vitro to induce H9c2 cells and neonatal rat left ventricular myocytes (NRVMs) to establish a cellular hypertrophy model. Results: Mass spectrometry revealed that the composition of GSLs was altered in pressure overload-induced hypertrophied mouse hearts and in stimulated hypertrophied cardiomyocyte cell lines. Specifically, in both cases, the proportion of endogenous lactosylceramide (LacCer) was significantly higher than in controls. Inhibition of GSL synthesis with Genz-123346 in NRVMs reduced cell hypertrophy, as well as fibrosis and apoptosis. By Western blotting, we detected decreased intracellular expression of Sirt3 and elevated phosphorylation of JNK after phenylephrine stimulation, but this was reversed in cells pretreated with Genz-123346. Additionally, increased protein expression of FoxO3a and Parkin, along with a decreased LC3-II/I protein ratio in phenylephrine-stimulated cells (compared with unstimulated cells), indicated that the mitochondrial autophagy process was disrupted; again, pretreatment with Genz-123346 reversed that. Discussion: Our results revealed that changes in GSLs in cardiomyocytes, especially an increase of LacCer, may be a factor causing cellular hypertrophy, which can be alleviated by inhibition of GSLs synthesis. A possible mechanism is that GSLs inhibition increases the expression of Sirt3 protein, scavenges intracellular reactive oxygen species, and restores mitochondrial autophagy homeostasis, thereby lessening cardiomyocyte hypertrophy. In all, these results provide a new perspective for developing drugs for cardiac hypertrophy.
RESUMO
A method for the rapid determination of α-tocopherol (α-T) and its oxidative products in plant tissue has been developed using supercritical fluid extraction (SFE) coupled with supercritical fluid chromatography (SFC) and medium vacuum chemical ionization (MVCI) with tandem mass spectrometry. The method is designed to study changes in levels for α-T and its oxidative products in plant cells during photosynthesis, aiming to observe the light response curves. α-T oxidation is a non-enzymatic self-defense mechanism in plant cells. Unlike enzyme-involved reactions, it cannot be stopped, so the oxidation continues in crude extracts even after extraction. Therefore, a real-time in-situ method is essential for tracking the light response curves. To optimize the selective reaction monitoring method, the reaction mixture of α-T and singlet oxygen (1O2), generated by rose Bengal under light illumination, was used as the source of oxidative products. The relative abundance changes in α-tocopherylquinone and 8a-hydroperoxy tocopherone in Pisum sativum L. (Pea) leaves under excessive light illumination have been preliminarily analyzed as part of the light response curve study. The method archives a throughput of 10-15 minutes for analyzing duplicate leaf samples. This process includes cutting off the leaf, sectioning it, placing the sample in a frozen SFE vessel, and conducting SFE/SFC analysis. Consequently, the average throughput is approximately 5-7 minutes per sample.
RESUMO
Background: Lung cancer deaths are increasing worldwide and the most common form of lung cancer treatment is chemotherapy. Pemetrexed (PMX) has been shown to be effective as a second-line treatment for advanced patients. Drugs can alter the expression of MicroRNAs, and MicroRNAs also can either enhance or reduce the drug's effectiveness and this is a two-way relationship. Hsa-MiR-320a is known to play a crucial role in the lung cancer. This study aims to investigate the expression of hsa-MiR-320a in lung cancer cells after treatment with PMX. Materials and Methods: A549 cells were cultured and treated with varying concentrations of PMX. Various parameters were measured, including cell viability, reactive oxygen species (ROS) production, lactate dehydrogenase (LDH) release, apoptosis assay, caspase 3 and 7 enzyme activity, and scratch assay. Additionally, gene expression profiles of hsa-MiR-320a, VDAC1, STAT3, BAX, and BCL2 were evaluated. Results: PMX reduced the viability and increased apoptosis. After 48 h, ROS production was 3.366-fold higher than in control cells and the LDH release rate was increased by 39%. PMX also up-regulated the expression of hsa-MiR-320a by about 12-fold change. Conclusion: Changes in the expression of MicroRNAs occur after chemotherapy, and these changes play a crucial role in regulating the growth of cancer cells. Identifying these MicroRNAs can be helpful in predicting the efficacy of the chemotherapy or introducing it as combination therapy. Our research has been shown that hsa-MiR-320a can serve as a biomarker of PMX efficacy and also has the potential to be used in combination therapy.
RESUMO
Nanotechnology has the advantages of enhanced bioactivity, reduced toxicity, target specificity, and sustained release and NPs can penetrate cell membranes. The small size of silver nanoparticles, AgNPs, large surface area, and unique physicochemical properties contribute to cell lysis and increased permeability of cell membranes used in the field of biomedicine. Functional precursors integrate with phytochemicals to create distinctive therapeutic properties and the stability of the nanoparticles can be enhanced by Surface coatings and encapsulation methods, The current study explores the various synthesis methods and characterization techniques of silver nanoparticles (AgNPs) and highlights their intrinsic activity in therapeutic applications, Anti-cancer activity noted at a concentration range of 5-50 µg/ml and angiogenesis is mitigated at a dosage range of 10-50 µg/ml, Diabetes is controlled within the same concentration. Wound healing is improved at concentrations of 10-50 µg/ml and with a typical range of 10-08 µg/ml for bacteria with antimicrobial capabilities. Advancement of silver nanoparticles with a focus on the future use of AgNPs-coated wound dressings and medical devices to decrease the risk of infection. Chemotherapeutic drugs can be administered by AgNPs, which reduces adverse effects and an improvement in treatment outcomes. AgNPs have been found to improve cell proliferation and differentiation, making them beneficial for tissue engineering and regenerative medicine. Our study highlights emerging patterns and developments in the field of medicine, inferring potential future paths.
RESUMO
trans-2-Decenoic acid is a pivotal α,ß-medium-chain unsaturated fatty acid that serves as an essential intermediary in the synthesis of 10-hydroxy-2-decenoic acid and various pharmaceutical compounds. Biosynthesis yield of trans-2-decenoic acid by decanoic acid has significantly improved in recent years; however, the oxidative stress of Escherichia coli at high fatty acid concentrations restricts the conversion rate. Here, we introduced a combination of rational design and metabolic rewiring of the E. coli electron transport chain (ETC) to improve trans-2-decenoic acid production. Overexpressing ubiquinone (UbQ) biosynthesis genes enhanced the expression of ETC complex III: UbQ to reduce reactive oxygen species (ROS) accumulation. Furthermore, applying rotenone to inhibit ETC complex I improved the electron transfer efficiency of complex II. The integration of Vitamin B5 and B2 into the fermentation process increased the activities of fatty acyl-CoA synthetase (MaMACS) and fatty acyl-CoA dehydrogenase (PpfadE). Finally, the constructed E. coli BL21(DE3)(ΔfadBJR/pCDFDuet-1-PpfadE-MaMACS/pRSFDuet-1-sumo-CtydiI-ubiI) strain exhibited a 51.50% decrease in ROS and a 93.33% enhancement in trans-2-decenoic acid yield, reaching 1.45 g/L after 66 h, which is the highest yield reported for flask fermentation. This study reports the feasibility of rewiring the ETC regulation and energy metabolism to improve α,ß-UCA biosynthesis efficiency.