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Drug Design, Development and Therapy 2024Anthraquinone drugs are widely used in the treatment of tumors. However, multidrug resistance and severe cardiac toxicity limit its use, which have led to the discovery...
BACKGROUND
Anthraquinone drugs are widely used in the treatment of tumors. However, multidrug resistance and severe cardiac toxicity limit its use, which have led to the discovery of new analogues. In this paper, 4-Deoxy--pyrromycinone (4-Deo), belonging to anthraquinone compounds, was first been studied with the anti-tumor effects and the safety in vitro and in vivo as a new anti-tumor drug or lead compound.
METHODS
The quantitative analysis of 4-Deo was established by UV methodology. The anti-cancer effect of 4-Deo in vitro was evaluated by cytotoxicity experiments of H22, HepG2 and Caco2, and the anti-cancer mechanism was explored by cell apoptosis and cycle. The tumor-bearing mouse model was established by subcutaneous inoculation of H22 cells to evaluate the anti-tumor effect of 4-Deo in vivo. The safety of 4-Deo was verified by the in vitro safety experiments of healthy cells and the in vivo safety experiments of H22 tumor-bearing mice. Tumor tissue sections were labeled with CRT, HMGB1, IL-6 and CD115 to explore the preliminary anti-cancer mechanism by immunohistochemistry.
RESULTS
In vitro experiments demonstrated that 4-Deo could inhibit the growth of H22 by inducing cell necrosis and blocking cells in S phase, and 4-Deo has less damage to healthy cells. In vivo experiments showed that 4-Deo increased the positive area of CRT and HMGB1, which may inhibit tumor growth by triggering immunogenic cell death (ICD). In addition, 4-Deo reduced the positive area of CSF1R, and the anti-tumor effect may be achieved by blocking the transformation of tumor-associated macrophages (TAMs) to M2 phenotype.
CONCLUSION
In summary, this paper demonstrated the promise of 4-Deo for cancer treatment in vitro and in vivo. This paper lays the foundation for the study of 4-Deo, which is beneficial for the further development anti-tumor drugs based on the lead compound of 4-Deo.
Topics: Animals; Humans; Antineoplastic Agents; Mice; Cell Proliferation; Apoptosis; Drug Screening Assays, Antitumor; Anthraquinones; Dose-Response Relationship, Drug; Molecular Structure; Structure-Activity Relationship; Mice, Inbred BALB C
PubMed: 38911033
DOI: 10.2147/DDDT.S461594 -
Stem Cell Research & Therapy Jun 2024Adult skeletal muscle contains resident muscle stem cells (MuSC) with high myogenic and engraftment potentials, making them suitable for cell therapy and regenerative...
BACKGROUND
Adult skeletal muscle contains resident muscle stem cells (MuSC) with high myogenic and engraftment potentials, making them suitable for cell therapy and regenerative medicine approaches. However, purification process of MuSC remains a major hurdle to their use in the clinic. Indeed, muscle tissue enzymatic dissociation triggers a massive activation of stress signaling pathways, among which P38 and JNK MAPK, associated with a premature loss of MuSC quiescence. While the role of these pathways in the myogenic progression of MuSC is well established, the extent to which their dissociation-induced activation affects the functionality of these cells remains unexplored.
METHODS
We assessed the effect of P38 and JNK MAPK induction on stemness marker expression and MuSC activation state during isolation by pharmacological approaches. MuSC functionality was evaluated by in vitro assays and in vivo transplantation experiments. We performed a comparative analysis of the transcriptome of human MuSC purified with pharmacological inhibitors of P38 and JNK MAPK (SB202190 and SP600125, respectively) versus available RNAseq resources.
RESULTS
We monitored PAX7 protein levels in murine MuSC during muscle dissociation and demonstrated a two-step decline partly dependent on P38 and JNK MAPK activities. We showed that simultaneous inhibition of these pathways throughout the MuSC isolation process preserves the expression of stemness markers and limits their premature activation, leading to improved survival and amplification in vitro as well as increased engraftment in vivo. Through a comparative RNAseq analysis of freshly isolated human MuSC, we provide evidence that our findings in murine MuSC could be relevant to human MuSC. Based on these findings, we implemented a purification strategy, significantly improving the recovery yields of human MuSC.
CONCLUSION
Our study highlights the pharmacological limitation of P38 and JNK MAPK activities as a suitable strategy to qualitatively and quantitatively ameliorate human MuSC purification process, which could be of great interest for cell-based therapies.
Topics: p38 Mitogen-Activated Protein Kinases; Animals; Humans; Mice; MAP Kinase Signaling System; Muscle, Skeletal; Stem Cells; Cell Differentiation; Mice, Inbred C57BL; Male; Anthracenes; JNK Mitogen-Activated Protein Kinases
PubMed: 38902774
DOI: 10.1186/s13287-024-03795-0 -
Molecules (Basel, Switzerland) May 2024In aqueous and solid media, 2-HP-β/γ-CD inclusion complexes with poly aromatic hydrocarbon (PAH) Phenanthrene (PHN), Anthracene (ANT), Benz(a)pyrene (BaP), and...
In aqueous and solid media, 2-HP-β/γ-CD inclusion complexes with poly aromatic hydrocarbon (PAH) Phenanthrene (PHN), Anthracene (ANT), Benz(a)pyrene (BaP), and Fluoranthene (FLT) were investigated for the first time. The inclusion complexes were characterized and investigated using fluorescence and HNMR spectroscopy. The most prevalent complexes consisting of both guests and hosts were those with a 1:1 guest-to-host ratio. The stability constants for the complexes of PHN with 2-HP-β-CD and 2-HP-γ-CD were 85 ± 12 M and 49 ± 29 M, respectively. Moreover, the stability constants were found to be 502 ± 46 M and 289 ± 44 M for the complexes of ANT with both hosts. The stability constants for the complexes of BaP with 2-HP-β-CD and 2-HP-γ-CD were (1.5 ± 0.02) × 10 M and (9.41 ± 0.03) × 10 M, respectively. The stability constant for the complexes of FLT with 2-HP-β-CD was (1.06 ± 0.06) × 10 M. However, FLT was observed to form a weak complex with 2-HP-γ-CD. Molecular dynamic (MD) simulations were used to investigate the mechanism and mode of inclusion processes, and to monitor the atomic-level stability of these complexes. The analysis of MD trajectories demonstrated that all guests formed stable inclusion complexes with both hosts throughout the duration of the simulation time, confirming the experimental findings. However, the flexible Hydroxypropyl arms prevented the PAHs from being encapsulated within the cavity; however, a stable exclusion complex was observed. The main forces that influenced the complexation included van der Waals interactions, hydrophobic forces, and C-H⋯π interaction, which contribute to the stability of these complexes.
PubMed: 38893410
DOI: 10.3390/molecules29112535 -
Journal of Environmental Health Science... Jun 2024Cooking is a significant source of polycyclic aromatic hydrocarbon (PAHs) emissions in indoor environments. A one-month biomonitoring study was carried out in previously...
Cooking is a significant source of polycyclic aromatic hydrocarbon (PAHs) emissions in indoor environments. A one-month biomonitoring study was carried out in previously selected rural Hungarian kitchens to evaluate cooking-related PAHs concentrations in 4 common kitchen vegetables such as basil, parsley, rocket and chives. The study had two mainobjectives: firstly, to follow PAHs accumulation pattern and to find out if this pattern can be associated with different cooking habits. Also, the usefulness of culinary herbs for indoor bioaccumulation studies was assessed. The 2-ring naphthalene was the dominant PAH in the majority of the samples, its concentrations were in the range of 25.4 µg/kg and 274 µg/kg, of 3-ring PAHs the prevalency of phenanthrene was observed, with highest concentration of 62 µg/kg. PAHs accumulation pattern in tested plants clearly indicated differences in cooking methods and cooking oils used in the selected households. Use of lard and animal fats in general resulted in the high concentrations of higher molecular weight (5- and 6-ring) PAHs, while olive oil usage could be associated with the emission of 2- and 3-ring PAHs. Culinary herbs, however, accumulated carcinogenic PAHs such as benzo[a]anthracene (highest concentration 11.9 µg/kg), benzo[b]fluoranthene (highest concentration 13.8 µg/kg) and chrysene (highest concentration 20.1 µg/kg) which might question their safe use.
PubMed: 38887758
DOI: 10.1007/s40201-024-00898-x -
Chemical Science Jun 2024Controlling chemical functionalization and achieving stable electrode-molecule interfaces for high-performance electrochemical energy storage applications remain...
Controlling chemical functionalization and achieving stable electrode-molecule interfaces for high-performance electrochemical energy storage applications remain challenging tasks. Herein, we present a simple, controllable, scalable, and versatile electrochemical modification approach of graphite rods (GRs) extracted from low-cost Eveready cells that were covalently modified with anthracene oligomers. The anthracene oligomers with a total layer thickness of ∼24 nm on the GR electrode yield a remarkable specific capacitance of ∼670 F g with good galvanostatic charge-discharge cycling stability (10 000) recorded in 1 M HSO electrolyte. Such a boost in capacitance is attributed mainly to two contributions: (i) an electrical double-layer at the anthracene oligomer/GR/electrolyte interfaces, and (ii) the proton-coupled electron transfer (PCET) reaction, which ensures a substantial faradaic contribution to the total capacitance. Due to the higher conductivity of the anthracene films, it possesses more azo groups (-N[double bond, length as m-dash]N-) during the electrochemical growth of the oligomer films compared to pyrene and naphthalene oligomers, which is key to PCET reactions. AC-based electrical studies unravel the in-depth charge interfacial electrical behavior of anthracene-grafted electrodes. Asymmetrical solid-state supercapacitor devices were made using anthracene-modified biomass-derived porous carbon, which showed improved performance with a specific capacitance of ∼155 F g at 2 A g with an energy density of 5.8 W h kg at a high-power density of 2010 W kg and powered LED lighting for a longer period. The present work provides a promising metal-free approach in developing organic thin-film hybrid capacitors.
PubMed: 38873075
DOI: 10.1039/d4sc00611a -
Scientific Reports Jun 2024Broad-spectrum biocatalysts enzymes, Laccases, have been implicated in the complete degradation of harmful pollutants into less-toxic compounds. In this study, two...
Broad-spectrum biocatalysts enzymes, Laccases, have been implicated in the complete degradation of harmful pollutants into less-toxic compounds. In this study, two extracellularly produced Laccases were purified to homogeneity from two different Ascomycetes spp. Trichoderma lixii FLU1 (TlFLU1) and Talaromyces pinophilus FLU12 (TpFLU12). The purified enzymes are monomeric units, with a molecular mass of 44 kDa and 68.7 kDa for TlFLU1 and TpFLU12, respectively, on SDS-PAGE and zymogram. It reveals distinct properties beyond classic protein absorption at 270-280 nm, with TlFLU1's peak at 270 nm aligning with this typical range of type II Cu site (white Laccase), while TpFLU12's unique 600 nm peak signifies a type I Cu site (blue Laccase), highlighting the diverse spectral fingerprints within the Laccase family. The K and k values revealed that ABTS is the most suitable substrate as compared to 2,6-dimethoxyphenol, caffeic acid and guaiacol for both Laccases. The bioinformatics analysis revealed critical His, Ile, and Arg residues for copper binding at active sites, deviating from the traditional two His and a Cys motif in some Laccases. The predicted biological functions of the Laccases include oxidation-reduction, lignin metabolism, cellular metal ion homeostasis, phenylpropanoid catabolism, aromatic compound metabolism, cellulose metabolism, and biological adhesion. Additionally, investigation of degradation of polycyclic aromatic hydrocarbons (PAHs) by purified Laccases show significant reductions in residual concentrations of fluoranthene and anthracene after a 96-h incubation period. TlFLU1 Laccase achieved 39.0% and 44.9% transformation of fluoranthene and anthracene, respectively, while TpFLU12 Laccase achieved 47.2% and 50.0% transformation, respectively. The enzyme structure-function relationship study provided insights into the catalytic mechanism of these Laccases for possible biotechnological and industrial applications.
Topics: Talaromyces; Laccase; Trichoderma; Fungal Proteins; Substrate Specificity; Copper; Kinetics; Oxidoreductases; Catalytic Domain
PubMed: 38862560
DOI: 10.1038/s41598-024-63959-z -
Redox Report : Communications in Free... Dec 2024Emodin is a naturally occurring anthraquinone derivative with a wide range of pharmacological activities, including neuroprotective and anti-inflammatory activities. We...
Emodin is a naturally occurring anthraquinone derivative with a wide range of pharmacological activities, including neuroprotective and anti-inflammatory activities. We aim to assess the anticancer activity of emodin against hepatocellular carcinoma (HCC) in rat models using the proliferation, invasion, and angiogenesis biomarkers. After induction of HCC, assessment of the liver impairment and the histopathology of liver sections were investigated. Hepatic expression of both mRNA and protein of the oxidative stress biomarkers, HO-1, Nrf2; the mitogenic activation biomarkers, ERK5, PKCδ; the tissue destruction biomarker, ADAMTS4; the tissue homeostasis biomarker, aggregan; the cellular fibrinolytic biomarker, MMP3; and of the cellular angiogenesis biomarker, VEGF were measured. Emodin increased the survival percentage and reduced the number of hepatic nodules compared to the HCC group. Besides, emodin reduced the elevated expression of both mRNA and proteins of all PKC, ERK5, ADAMTS4, MMP3, and VEGF compared with the HCC group. On the other hand, emodin increased the expression of mRNA and proteins of Nrf2, HO-1, and aggrecan compared with the HCC group. Therefore, emodin is a promising anticancer agent against HCC preventing the cancer prognosis and infiltration. It works through many mechanisms of action, such as blocking oxidative stress, proliferation, invasion, and angiogenesis.
Topics: Animals; Emodin; Carcinoma, Hepatocellular; Rats; Thioacetamide; Liver Neoplasms; Antioxidants; ADAMTS4 Protein; Male; Protein Kinase C; Oxidative Stress; Antineoplastic Agents; Signal Transduction; Cell Proliferation
PubMed: 38861483
DOI: 10.1080/13510002.2024.2365590 -
RSC Advances Jun 2024The aim of this study was to develop a new method for sampling and analyzing polycyclic aromatic hydrocarbons in the air. This was achieved by utilizing a needle trap...
The aim of this study was to develop a new method for sampling and analyzing polycyclic aromatic hydrocarbons in the air. This was achieved by utilizing a needle trap device packed with a modified porous aromatic framework coated with magnetic nanoparticles (PAF-6-MNPs). The modified adsorbent underwent qualitative evaluation using Fourier-transform infrared spectroscopy and X-ray diffraction, as well as scanning and transmission electron microscopy. The optimal conditions for sampling polycyclic aromatic hydrocarbons compounds were determined using a dynamic atmosphere chamber. The method was validated by taking various samples from the standard chamber, and then analyzed under different environmental sampling conditions using a gas chromatography device. The limit of detection (LOD) and limit of quantification (LOQ) values for the analytes of interest, including naphthalene, anthracene, and pyrene, ranged from 0.0034-0.0051 and 0.010-0.015 μg L, respectively. Also, the repeatability and reproducibility of the method expressed as relative standard deviation, for the mentioned analyses were found to be in the range of 17.8-20.5% and 20-22.9%. The results indicated that over a 20 day storage period (with the needle trap device containing the analytes of interest kept in the refrigerator), there was no significant decrease in the amount of analytes compared to the initial amount. These findings suggest that, the needle trap packed with the proposed adsorbent offers a reliable, highly-sensitive, easy-to-use, and cost-effective method for sampling polycyclic aromatic hydrocarbons in the air compared to the conventional method recommended by the National Institute of Occupational Safety and Health (NIOSH), method 5515.
PubMed: 38860255
DOI: 10.1039/d4ra01651c -
Scientific Reports Jun 2024This study investigates the environmental impact of burning herbicide-contaminated biomass, focusing on atrazine (ATZ) and diuron (DIU) sprayed on rice straw prior to...
This study investigates the environmental impact of burning herbicide-contaminated biomass, focusing on atrazine (ATZ) and diuron (DIU) sprayed on rice straw prior to burning. Samples of soil, biomass residues, total suspended particulate (TSP), particulate matter with an aerodynamic diameter ≤ 10 µm (PM), and aerosols were collected and analyzed. Soil analysis before and after burning contaminated biomass showed significant changes, with 2,4-dichlorophenoxyacetic acid (2,4-D) initially constituting 79.2% and decreasing by 3.3 times post-burning. Atrazine-desethyl, sebuthylazine, and terbuthylazine were detected post-burning. In raw rice straw biomass, terbuthylazine dominated at 80.0%, but burning ATZ-contaminated biomass led to the detection of atrazine-desethyl and notable increases in sebuthylazine and terbuthylazine. Conversely, burning DIU-contaminated biomass resulted in a shift to 2,4-D dominance. Analysis of atmospheric components showed changes in TSP, PM, and aerosol samples. Linuron in ambient TSP decreased by 1.6 times after burning ATZ-contaminated biomass, while atrazine increased by 2.9 times. Carcinogenic polycyclic aromatic hydrocarbons (PAHs), including benzo[a]anthracene (BaA), benzo[a]pyrene (BaP), and benzo[b]fluoranthene (BbF), increased by approximately 9.9 to 13.9 times after burning ATZ-contaminated biomass. In PM, BaA and BaP concentrations increased by approximately 11.4 and 19.0 times, respectively, after burning ATZ-contaminated biomass. This study sheds light on the environmental risks posed by burning herbicide-contaminated biomass, emphasizing the need for sustainable agricultural practices and effective waste management. The findings underscore the importance of regulatory measures to mitigate environmental contamination and protect human health.
Topics: Atrazine; Oryza; Herbicides; Biomass; Soil; Diuron; Soil Pollutants; Air Pollutants; Environmental Monitoring; Particulate Matter
PubMed: 38858445
DOI: 10.1038/s41598-024-64291-2 -
ACS Omega Jun 2024The stability of both the structure and activity of MoS nanocatalysts is crucial for minimizing the catalyst cost of the slurry-phase (SP) catalytic hydrogenation....
The stability of both the structure and activity of MoS nanocatalysts is crucial for minimizing the catalyst cost of the slurry-phase (SP) catalytic hydrogenation. MoS-GP and MoS-SP catalysts were, respectively, obtained by gas-phase (denoted as GP) and SP aging of fresh MoS catalysts. The MoS-SP catalyst demonstrated a comparable catalytic hydrogenation activity to that of the fresh MoS catalyst, which is about 1.7 times of that for the MoS-GP catalyst. After 12 cycles of the MoS-SP catalyst, the obtained Cy12 catalyst demonstrates a retention of 92.0% of its initial catalytic activity. The MoS-SP catalyst exhibits an impressive stability of catalytic hydrogenation. The MoS-SP catalyst exhibits average stacking layers of 3.3 and an average slab of 5.2 nm and exposes 14.0% of active sites. The MoS-SP catalyst can serve as a highly active and stable catalyst for catalytic hydrogenation. This finding can offer valuable insights into the stability of the hydrogenation catalyst in SP hydrogenation technology.
PubMed: 38854572
DOI: 10.1021/acsomega.4c01846