-
International Journal of Medical... 2024: Breast cancer results from tissue degradation caused by environmental and genetic factors that affect cells in the body. Matrix metalloproteinases, such as MMP-2 and...
: Breast cancer results from tissue degradation caused by environmental and genetic factors that affect cells in the body. Matrix metalloproteinases, such as MMP-2 and MMP-9, are considered potential putative markers for tumor diagnosis in clinical validation due to their easy detection in body fluids. In addition, recent reports have suggested multiple roles for MMPs, rather than simply degeneration of the extracellular matrix, which comprises mobilizing growth factors and processing surface molecules. : In this study, the chemotherapeutic effects of anthraquinone (AQ) extracted from edible mushrooms ( Jacq. ex Fr.) cells was examined in MCF-7 breast cancer cells. The cytotoxic potential and oxidative stress induced by purified anthraquinone were assessed in MCF-7 cells using MTT and ROS estimation assays. Gelatin Zymography, and DNA fragmentation assays were performed to examine expression and apoptotic induction in the MCF-7 cells treated with AQ. The genes crucial for mutations were examined, and the mutated RNA knockout plausibility was analyzed using the CRISPR spcas9 genome editing software. : MCF-7 cells were attenuated in a concentration-dependent manner by the administration of AQ purified from compared with the standard anticancer drug paclitaxel. AQ supplementation decreased oxidative stress and mitochondrial impairment in MCF-7 cells. Treatment with AQ and AQ with paclitaxel consistently decreased the expression of crucial marker genes such as and . The mutated genes , , and were assessed and observed to reveal four putative gene knockdown potentials for breast cancer treatment. : The synergistic application of AQ and paclitaxel exerted a strong inhibitory effect on the MCF-7 breast cancer cells. Extensive studies are imperative to better understand the action of bioactive mixes on the edible oyster fungus . The gene knockout potential detected by CRISPR SpCas9 will aid in elite research into anticancer treatments.
Topics: Humans; Breast Neoplasms; Anthraquinones; MCF-7 Cells; Matrix Metalloproteinase 9; Female; Apoptosis; Matrix Metalloproteinase 2; Pleurotus; Gene Expression Regulation, Neoplastic; Oxidative Stress
PubMed: 38774755
DOI: 10.7150/ijms.93334 -
Scientific Reports May 2024Polycyclic aromatic hydrocarbons (PAHs) are highly toxic, carcinogenic substances. On soils contaminated with PAHs, crop cultivation, animal husbandry and even the...
Polycyclic aromatic hydrocarbons (PAHs) are highly toxic, carcinogenic substances. On soils contaminated with PAHs, crop cultivation, animal husbandry and even the survival of microflora in the soil are greatly perturbed, depending on the degree of contamination. Most microorganisms cannot tolerate PAH-contaminated soils, however, some microbial strains can adapt to these harsh conditions and survive on contaminated soils. Analysis of the metagenomes of contaminated environmental samples may lead to discovery of PAH-degrading enzymes suitable for green biotechnology methodologies ranging from biocatalysis to pollution control. In the present study, our goal was to apply a metagenomic data search to identify efficient novel enzymes in remediation of PAH-contaminated soils. The metagenomic hits were further analyzed using a set of bioinformatics tools to select protein sequences predicted to encode well-folded soluble enzymes. Three novel enzymes (two dioxygenases and one peroxidase) were cloned and used in soil remediation microcosms experiments. The experimental design of the present study aimed at evaluating the effectiveness of the novel enzymes on short-term PAH degradation in the soil microcosmos model. The novel enzymes were found to be efficient for degradation of naphthalene and phenanthrene. Adding the inorganic oxidant CaO further increased the degrading potential of the novel enzymes for anthracene and pyrene. We conclude that metagenome mining paired with bioinformatic predictions, structural modelling and functional assays constitutes a powerful approach towards novel enzymes for soil remediation.
Topics: Metagenomics; Biodegradation, Environmental; Soil Microbiology; Polycyclic Aromatic Hydrocarbons; Soil Pollutants; Soil; Dioxygenases; Phenanthrenes; Naphthalenes; Metagenome
PubMed: 38773163
DOI: 10.1038/s41598-024-61566-6 -
Ecotoxicology and Environmental Safety Jul 2024Rhubarb is widely used in health care, but causing a great amount of rhein-containing herbal residue. Rhein with several toxicities might pollute environment, damage...
Rhubarb is widely used in health care, but causing a great amount of rhein-containing herbal residue. Rhein with several toxicities might pollute environment, damage ecology and even hazard human health if left untreated. In this study, the degradation effects of bisulfite- (BS) and peroxymonosulfate- (PMS) based oxidation systems on rhein in rhubarb residue were compared and investigated. The effects of BS and PMS with two valence states of ferric ion (Fe) on the degradation of rhein in rhubarb residue were optimized for the selection of optimal oxidation system. The influences of reaction temperature, reaction time and initial pH on the removal of rhein under the optimal oxidation system were evaluated. The chemical profiles of rhubarb residue with and without oxidation process were compared by UPLC-QTOF-MS/MS, and the degradation effects were investigated by PLS-DA and S plot/OPLS-DA analysis. The results manifested that PMS showed relative higher efficiency than BS on the degradation of rhein. Moreover, Fe(III) promoted the degradation effect of PMS, demonstrated that Fe(III)/PMS is the optimal oxidation system to degrade rhein in rhubarb residue. Further studies indicated that the degradation of rhein by the Fe(III)/PMS oxidation system was accelerated with the prolong of reaction time and the elevation of reaction temperature, and also affected by the initial pH. More importantly, Fe(III)/PMS oxidation system could degrade rhein in rhubarb residue completely under the optimal conditions. In conclusion, Fe(III)/PMS oxidation system is a feasible method to treat rhein in rhubarb residue.
Topics: Anthraquinones; Rheum; Oxidation-Reduction; Peroxides; Tandem Mass Spectrometry; Sulfites; Hydrogen-Ion Concentration; Ferric Compounds; Temperature
PubMed: 38772144
DOI: 10.1016/j.ecoenv.2024.116474 -
Ecotoxicology and Environmental Safety Jul 2024The purpose of this study is to evaluate the decolorization ability and detoxification effect of LAC-4 laccase on various types of single and mixed dyes, and lay a good...
The purpose of this study is to evaluate the decolorization ability and detoxification effect of LAC-4 laccase on various types of single and mixed dyes, and lay a good foundation for better application of laccase in the efficient treatment of dye pollutants. The reaction system of the LAC-4 decolorizing single dyes (azo, anthraquinone, triphenylmethane, and indigo dyes, 17 dyes in total) were established. To explore the decolorization effect of the dye mixture by LAC-4, two dyes of the same type or different types were mixed at the same concentration (100 mg/L) in the reaction system containing 0.5 U laccase, and time-course decolorization were performed on the dye mixture. The combined dye mixtures consisted of azo + azo, azo + anthraquinone, azo + indigo, azo + triphenylmethane, indigo + triphenylmethane, and triphenylmethane + triphenylmethane. The results obtained in this study were as follows. Under optimal conditions of 30 °C and pH 5.0, LAC-4 (0.5 U) can efficiently decolorize four different types of dyes. The 24-hour decolorization efficiencies of LAC-4 for 800 mg/L Orange G and Acid Orange 7 (azo), Remazol Brilliant Blue R (anthraquinone), Bromophenol Blue and Methyl Green (triphenylmethane), and Indigo Carmine (indigo) were 75.94%, 93.30%, 96.56%, 99.94%, 96.37%, and 37.23%, respectively. LAC-4 could also efficiently decolorize mixed dyes with different structures. LAC-4 can achieve a decolorization efficiency of over 80% for various dye mixtures such as Orange G + Indigo Carmine (100 mg/L+100 mg/L), Reactive Orange 16 + Methyl Green (100 mg/L+100 mg/L), and Remazol Brilliant Blue R + Methyl Green (100 mg/L+100 mg/L). During the decolorization process of the mixed dyes by laccase, four different interaction relationships were observed between the dyes. Decolorization efficiencies and rates of the dyes that were difficult to be degraded by laccase could be greatly improved when mixed with other dyes. Degradable dyes could greatly enhance the ability of LAC-4 to decolorize extremely difficult-to-degrade dyes. It was also found that the decolorization efficiencies of the two dyes significantly increased after mixing. The possible mechanisms underlying the different interaction relationships were further discussed. Free, but not immobilized, LAC-4 showed a strong continuous batch decolorization ability for single dyes, two-dye mixtures, and four-dye mixtures with different structures. LAC-4 exhibited high stability, sustainable degradability, and good reusability in the continuous batch decolorization. The LAC-4-catalyzed decolorization markedly reduced or fully abolished the toxic effects of single dyes (azo, anthraquinone, and indigo dye) and mix dyes (nine dye mixtures containing four structural types of dyes) on plants. Our findings indicated that LAC-4 laccase had significant potential for use in bioremediation due to its efficient degradation and detoxification of single and mixed dyes with different structural types.
Topics: Coloring Agents; Laccase; Azo Compounds; Reishi; Trityl Compounds; Water Pollutants, Chemical; Biodegradation, Environmental; Anthraquinones; Indigo Carmine; Hydrogen-Ion Concentration; Water Decolorization; White
PubMed: 38768540
DOI: 10.1016/j.ecoenv.2024.116450 -
Scientific Reports May 2024Robust solid-core silica particles with submicrometer size and anthracene-containing mesoporous shell were obtained and studied as model water-dispersable photoreactors....
Robust solid-core silica particles with submicrometer size and anthracene-containing mesoporous shell were obtained and studied as model water-dispersable photoreactors. An anthracene derivative containing a triethoxysilyl group was synthesized and co-condensed with tetraethoxysilane in various ratios to form a photoactive mesoporous shell with a thickness up to approximately 80 nm on previously prepared solid silica particles. Mesopores of as-synthesized particles, without a commonly applied removal of the micellar templates, offered a confined space for solubilization of hydrophobic molecules. Efficient excitation energy transfer from anthracene chromophores to both hydrophobic (perylene) and hydrophilic (fluoresceine) encapsulated acceptors was observed in an aqueous dispersion of the particles. Photosensitized oxidation of encapsulated perylene was shown to proceed efficiently in such systems serving as water-dispersable photoreactors. Importantly, the designed core-shell systems were found to be stable for a long time (at least 24 months) and robust enough, thanks to the presence of solid cores, to be handled by centrifugation in aqueous dispersions. All these features make them promising candidates for reusable systems for the photosensitized degradation of water pollutants, especially hydrophobic pollutants.
PubMed: 38755207
DOI: 10.1038/s41598-024-61750-8 -
Free Radical Biology & Medicine Aug 2024Photodynamic therapy is a noninvasive treatment in which specific photosensitizers and light are used to produce high amounts of reactive oxygen species (ROS), which can...
Photodynamic therapy is a noninvasive treatment in which specific photosensitizers and light are used to produce high amounts of reactive oxygen species (ROS), which can be employed for targeted tissue destruction in cancer treatment or antimicrobial therapy. However, it remains unknown whether lower amounts of ROS produced by mild photodynamic therapy increase lifespan and stress resistance at the organism level. Here, we introduce a novel photodynamic treatment (PDTr) that uses 20 μM hypericin, a photosensitizer that originates from Hypericum perforatum, and orange light (590 nm, 5.4 W/m, 1 min) to induce intracellular ROS formation (ROS), thereby resulting in lifespan extension and improved stress resistance in C. elegans. The PDTr-induced increase in longevity was abrogated by N-acetyl cysteine, suggesting the hormetic response was driven by prooxidative mechanisms. PDTr activated the translocation of SKN-1/NRF-2 and DAF-16/FOXO, leading to elevated expression of downstream oxidative stress-responsive genes, including ctl-1, gst-4, and sod-3. In summary, our findings suggest a novel PDTr method that extends the lifespan of C. elegans under both normal and oxidative stress conditions through the activation of SKN-1 and DAF-16 via the involvement of many antioxidant genes.
Topics: Animals; Caenorhabditis elegans; Oxidative Stress; Longevity; Caenorhabditis elegans Proteins; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Transcription Factors; Perylene; Anthracenes; Forkhead Transcription Factors; DNA-Binding Proteins; Superoxide Dismutase; NF-E2-Related Factor 2; Gene Expression Regulation; Light; Acetylcysteine
PubMed: 38754743
DOI: 10.1016/j.freeradbiomed.2024.05.023 -
Journal of Nanobiotechnology May 2024Chemotherapy, the mainstay treatment for metastatic cancer, presents serious side effects due to off-target exposure. In addition to the negative impact on patients'...
BACKGROUND
Chemotherapy, the mainstay treatment for metastatic cancer, presents serious side effects due to off-target exposure. In addition to the negative impact on patients' quality of life, side effects limit the dose that can be administered and thus the efficacy of the drug. Encapsulation of chemotherapeutic drugs in nanocarriers is a promising strategy to mitigate these issues. However, avoiding premature drug release from the nanocarriers and selectively targeting the tumour remains a challenge.
RESULTS
In this study, we present a pioneering method for drug integration into nanoparticles known as mesoporous organosilica drugs (MODs), a distinctive variant of periodic mesoporous organosilica nanoparticles (PMOs) in which the drug is an inherent component of the silica nanoparticle structure. This groundbreaking approach involves the chemical modification of drugs to produce bis-organosilane prodrugs, which act as silica precursors for MOD synthesis. Mitoxantrone (MTO), a drug used to treat metastatic breast cancer, was selected for the development of MTO@MOD nanomedicines, which demonstrated a significant reduction in breast cancer cell viability. Several MODs with different amounts of MTO were synthesised and found to be efficient nanoplatforms for the sustained delivery of MTO after biodegradation. In addition, FeO NPs were incorporated into the MODs to generate magnetic MODs to actively target the tumour and further enhance drug efficacy. Importantly, magnetic MTO@MODs underwent a Fenton reaction, which increased cancer cell death twofold compared to non-magnetic MODs.
CONCLUSIONS
A new PMO-based material, MOD nanomedicines, was synthesised using the chemotherapeutic drug MTO as a silica precursor. MTO@MOD nanomedicines demonstrated their efficacy in significantly reducing the viability of breast cancer cells. In addition, we incorporated FeO into MODs to generate magnetic MODs for active tumour targeting and enhanced drug efficacy by ROS generation. These findings pave the way for the designing of silica-based multitherapeutic nanomedicines for cancer treatment with improved drug delivery, reduced side effects and enhanced efficacy.
Topics: Humans; Breast Neoplasms; Female; Cell Survival; Organosilicon Compounds; Antineoplastic Agents; Mitoxantrone; Cell Line, Tumor; Drug Carriers; Silicon Dioxide; Porosity; Drug Liberation; Nanoparticles; MCF-7 Cells; Nanomedicine; Reactive Oxygen Species
PubMed: 38745193
DOI: 10.1186/s12951-024-02522-4 -
European Journal of Histochemistry : EJH May 2024Chronic kidney disease (CKD) is a leading public health issue associated with high morbidity worldwide. However, there are only a few effective therapeutic strategies...
Emodin improves renal fibrosis in chronic kidney disease by regulating mitochondrial homeostasis through the mediation of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α).
Chronic kidney disease (CKD) is a leading public health issue associated with high morbidity worldwide. However, there are only a few effective therapeutic strategies for CKD. Emodin, an anthraquinone compound from rhubarb, can inhibit fibrosis in tissues and cells. Our study aims to investigate the antifibrotic effect of emodin and the underlying molecular mechanism. A unilateral ureteral obstruction (UUO)-induced rat model was established to evaluate the effect of emodin on renal fibrosis development. Hematoxylin and eosin staining, Masson's trichrome staining, and immunohistochemistry staining were performed to analyze histopathological changes and fibrotic features after emodin treatment. Subsequently, a transforming growth factor-beta 1 (TGF-β1)-induced cell model was used to assess the inhibition of emodin on cell fibrosis in vitro. Furthermore, Western blot analysis and real-time quantitative reverse transcription-polymerase chain reaction were performed to validate the regulatory mechanism of emodin on renal fibrosis progression. As a result, emodin significantly improved histopathological abnormalities in rats with UUO. The expression of fibrosis biomarkers and mitochondrial biogenesis-related proteins also decreased after emodin treatment. Moreover, emodin blocked TGF-β1-induced fibrotic phenotype, lipid accumulation, and mitochondrial homeostasis in NRK-52E cells. Conversely, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) silencing significantly reversed these features in emodin-treated cells. Collectively, emodin plays an important role in regulating PGC-1α-mediated mitochondria function and energy homeostasis. This indicates that emodin exhibits great inhibition against renal fibrosis and acts as a promising inhibitor of CKD.
Topics: Animals; Emodin; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Renal Insufficiency, Chronic; Fibrosis; Mitochondria; Male; Rats; Rats, Sprague-Dawley; Homeostasis; Kidney; Ureteral Obstruction; Transforming Growth Factor beta1; Cell Line
PubMed: 38742403
DOI: 10.4081/ejh.2024.3917 -
Journal of Medicine and Life Jan 2024This study aimed to identify novel Glyoxalase-I (Glo-I) inhibitors with potential anticancer properties, focusing on anthraquinone amide-based derivatives. We...
This study aimed to identify novel Glyoxalase-I (Glo-I) inhibitors with potential anticancer properties, focusing on anthraquinone amide-based derivatives. We synthesized a series of these derivatives and conducted in silico docking studies to predict their binding interactions with Glo-I. In vitro assessments were performed to evaluate the anti-Glo-I activity of the synthesized compounds. A comprehensive structure-activity relationship (SAR) analysis identified key features responsible for specific binding affinities of anthraquinone amide-based derivatives to Glo-I. Additionally, a 100 ns molecular dynamics simulation assessed the stability of the most potent compound compared to a co-crystallized ligand. Compound MQ3 demonstrated a remarkable inhibitory effect against Glo-I, with an IC concentration of 1.45 µM. The inhibitory potency of MQ3 may be attributed to the catechol ring, amide functional group, and anthraquinone moiety, collectively contributing to a strong binding affinity with Glo-I. Anthraquinone amide-based derivatives exhibit substantial potential as Glo-I inhibitors with prospective anticancer activity. The exceptional inhibitory efficacy of compound MQ3 indicates its potential as an effective anticancer agent. These findings underscore the significance of anthraquinone amide-based derivatives as a novel class of compounds for cancer therapy, supporting further research and advancements in targeting the Glo-I enzyme to combat cancer.
Topics: Humans; Amides; Anthraquinones; Antineoplastic Agents; Enzyme Inhibitors; Lactoylglutathione Lyase; Molecular Docking Simulation; Molecular Dynamics Simulation; Structure-Activity Relationship
PubMed: 38737655
DOI: 10.25122/jml-2023-0257 -
International Journal of Molecular... Apr 2024Familial Alzheimer's disease (FAD) is a complex and multifactorial neurodegenerative disorder for which no curative therapies are yet available. Indeed, no single...
Familial Alzheimer's disease (FAD) is a complex and multifactorial neurodegenerative disorder for which no curative therapies are yet available. Indeed, no single medication or intervention has proven fully effective thus far. Therefore, the combination of multitarget agents has been appealing as a potential therapeutic approach against FAD. Here, we investigated the potential of combining tramiprosate (TM), curcumin (CU), and the JNK inhibitor SP600125 (SP) as a treatment for FAD. The study analyzed the individual and combined effects of these two natural agents and this pharmacological inhibitor on the accumulation of intracellular amyloid beta iAβ; hyperphosphorylated protein TAU at Ser/Thr; mitochondrial membrane potential (ΔΨ); generation of reactive oxygen species (ROS); oxidized protein DJ-1; proapoptosis proteins p-c-JUN at Ser/Ser, TP53, and cleaved caspase 3 (CC3); and deficiency in acetylcholine (ACh)-induced transient Ca influx response in cholinergic-like neurons (ChLNs) bearing the mutation I416T in presenilin 1 (PSEN1 I416T). We found that single doses of TM (50 μM), CU (10 μM), or SP (1 μM) were efficient at reducing some, but not all, pathological markers in PSEN 1 I416T ChLNs, whereas a combination of TM, CU, and SP at a high (50, 10, 1 μM) concentration was efficient in diminishing the iAβ, p-TAU Ser/Thr, DJ-1Cys-SO, and CC3 markers by -50%, -75%, -86%, and -100%, respectively, in PSEN1 I417T ChLNs. Although combinations at middle (10, 2, 0.2) and low (5, 1, 0.1) concentrations significantly diminished p-TAU Ser/Thr, DJ-1Cys-SO, and CC3 by -69% and -38%, -100% and -62%, -100% and -62%, respectively, these combinations did not alter the iAβ compared to untreated mutant ChLNs. Moreover, a combination of reagents at H concentration was able to restore the dysfunctional ACh-induced Ca influx response in PSEN 1 I416T. Our data suggest that the use of multitarget agents in combination with anti-amyloid (TM, CU), antioxidant (e.g., CU), and antiapoptotic (TM, CU, SP) actions might be beneficial for reducing iAβ-induced ChLN damage in FAD.
Topics: Curcumin; Alzheimer Disease; Presenilin-1; Anthracenes; Animals; Reactive Oxygen Species; Mice; Amyloid beta-Peptides; Humans; tau Proteins; Neurons; Membrane Potential, Mitochondrial; Taurine
PubMed: 38732141
DOI: 10.3390/ijms25094925