-
BioRxiv : the Preprint Server For... Jun 2024Polyamine metabolism and signaling play important roles in multiple cancers but have not previously been studied in Ewing sarcoma. Here, we show that blocking polyamine...
Polyamine metabolism and signaling play important roles in multiple cancers but have not previously been studied in Ewing sarcoma. Here, we show that blocking polyamine synthesis with D, L-alpha-difluoromethylornithine (DFMO) causes a G1 cell cycle arrest, dose-dependent decreases in sarcosphere formation from Ewing sarcoma cell lines growing in non-adherent conditions and a decrease in clonogenic growth in soft agar. Further, we utilized our orthotopic implantation/amputation model of Ewing sarcoma metastasis to demonstrate that DFMO slowed primary tumor growth in addition to limiting metastasis. RNA sequencing demonstrated gene expression patterns consistent with induction of ferroptosis caused by polyamine depletion. Induction of ferroptosis was validated in vitro by demonstrating that ferrostatin-1, an inhibitor of ferroptosis, allows sphere formation even in the presence of DFMO. Collectively, these results reveal a novel mechanism by which DFMO prevents metastasis - induction of ferroptosis due to polyamine depletion. Our results provide preclinical justification to test the ability of DFMO to prevent metastatic recurrence in Ewing sarcoma patients at high risk for relapse.
PubMed: 38948823
DOI: 10.1101/2024.06.14.599064 -
Journal of Oleo Science 2024In this study, we evaluated the cancer cell killing activity of koji mold-derived extracts using several solvents. The koji mold lipid extract (KML) exhibited potent...
Koji Mold-derived Lipids Disrupt the Intracellular Redox State by Decreasing the GPx4 and Intracellular Glutathione Levels, Promoting Membrane Lipid Peroxidation, and Inducing Ferroptosis in HL-60 Cells.
In this study, we evaluated the cancer cell killing activity of koji mold-derived extracts using several solvents. The koji mold lipid extract (KML) exhibited potent cytotoxicity against a human leukemia cell line. Fractionation of the KML via silica gel chromatography revealed the presence of active components in fraction (Fr.) 6. Cytotoxic effects of Fr. 6 were inhibited by the ferroptosis inhibitors, ferrostatin-1 and SRS11-92, and the iron chelator, deferoxamine. Interestingly, ferroptosis inhibitors failed to prevent the KML-induced cell death. Fr. 6 decreased the expression of glutathione peroxidase 4 (GPx4) and increased the level of peroxidized plasma membrane lipids. Furthermore, Fr. 6 decreased the intracellular glutathione levels. Overall, our results suggest that Fr. 6 included in KML induces ferroptosis in HL-60 cells.
Topics: Humans; HL-60 Cells; Phospholipid Hydroperoxide Glutathione Peroxidase; Ferroptosis; Lipid Peroxidation; Glutathione; Oxidation-Reduction; Deferoxamine; Cyclohexylamines; Lipids; Phenylenediamines; Membrane Lipids; Iron Chelating Agents
PubMed: 38945927
DOI: 10.5650/jos.ess24043 -
Plant Physiology and Biochemistry : PPB Jun 2024Eco-friendly and sustainable practices must be followed while using the right plants and microbes to remove harmful heavy metals from the soil. The goal of the current...
Eco-friendly and sustainable practices must be followed while using the right plants and microbes to remove harmful heavy metals from the soil. The goal of the current study was to ascertain how effectively sorghum plants removed cadmium (Cd) from the soil using polyamines and mycorrhiza. Plant-biochemicals such as free amino acids, ascorbic acids, anthocyanin, proline, and catalase, APX, peroxidase activities were considered as markers in this study which revealed the adverse plant growth performance under 70 and 150 ppm of Cd concentration (w/w) after 30,60, and 90 days of treatment. The plants showed a mitigating effect against high Cd-concentration with exogenous use of mycorrhiza and putrescine. The treatment T17 (mycorrhiza +5 mM putrescine) showed a substantial decrease in the content of total free amino acid, ascorbic acid, catalase, APX, peroxidase by 228.36%, 39.79%, 59.06%, 182.79% 106.97%, respectively after 90 days as compared to T12 (150 ppm Cd). Anthocyanin content was negatively correlated (-0.503, -0.556, and -0.613) at p < 0.01 with other studied markers, with an increase by 10.52% in T17 treated plant as compared to T12. The concentration of Cd in root increased by 49.6% (141 ppm) and decreased in the shoot by 71% (17.8 ppm) in T17 treated plant as compared to T12 after 90 days. The application of mycorrhiza and putrescine significantly increased BCF (>1) and decreased TF (<1) for Cd translocation. The administration of mycorrhiza and putrescine boosted the Cd removal efficiency of sorghum plants, according to FTIR, XRD, and DSC analysis. As a result, this study demonstrates novel approaches for induced phytoremediation activity of plants via mycorrhiza and putrescine augmentation, which can be a promising option for efficient bioremediation in contaminated sites.
PubMed: 38945095
DOI: 10.1016/j.plaphy.2024.108846 -
The Science of the Total Environment Jun 2024Microplastics (MPs) are particles with sizes of ≤5 mm formed when plastic materials break down. These contaminants are often found in marine environments, making it... (Review)
Review
Microplastics (MPs) are particles with sizes of ≤5 mm formed when plastic materials break down. These contaminants are often found in marine environments, making it easy for sea turtles to ingest them and for their microbiome to be exposed. MPs can disrupt microbiome balance, leading to dysbiosis and making organisms more susceptible to diseases. Owing to the significance of these processes, it is crucial to dedicate research to studying the metabolic and genetic analysis of the gut microbiome in sea turtles. The objective of this study was to describe the effects of exposure to MPs on the gut microbiome of sea turtles, based on current knowledge. This review also aimed to explore the potential link between MP exposure and disease susceptibility in these animals. We show that the metabolites produced by the gut microbiome, such as short-chain fatty acids (SCFAs), polyamines, and polysaccharide A, can regulate the expression of host genes. Regulation occurs through various mechanisms, including histone acetylation, DNA methylation, and the modulation of cytokine gene expression. These processes are essential for preserving the integrity of the gut mucosa and enhancing the functionality of immune cells. Exposure to MPs disrupts the gut microbiome and alters gene expression, leading to immune system disturbances in sea turtles. This vulnerability makes turtles more susceptible to opportunistic microorganisms such as chelonid alphaherpesvirus 5 (ChAHV5), which is linked to the development of fibropapillomatosis (FP). Additionally, targeted dietary interventions or the use of live microorganisms such as probiotics can help restore microbial biodiversity and recover lost metabolic pathways. The goal of these interventions is to restore the functionality of the immune system in sea turtles undergoing rehabilitation at specialized centers. The gut microbiome plays a crucial role in sea turtle health, sparking discussions and investigations that can potentially lead to promising treatments for these animals.
PubMed: 38944299
DOI: 10.1016/j.scitotenv.2024.174298 -
ChemPlusChem Jun 2024The new ligand 3,3'-bis(((2-(3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-6-yl)ethyl)amino)methyl)-[1,1'-biphenyl]-2,2'-diol (L) has been synthesized and characterized. It...
The new ligand 3,3'-bis(((2-(3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-6-yl)ethyl)amino)methyl)-[1,1'-biphenyl]-2,2'-diol (L) has been synthesized and characterized. It contains two pyridinacyclophane macrocycles spaced by a 2,2'-biphenol moiety. The acid-base behaviour of L as well as its binding properties towards Zn2+ ion have been investigated. This work is inserted in the field of fluorescent ditopic receptors, formed by two polyamines spaced by a aromatic fragments. This ligand represents a new example of a peculiar case of polyamine fluorescent receptor in which the interaction with Zn2+ is translated into a deactivation of the emission. Enough data to describe and explain this unusual behaviour was obtained through potentiometric, UV-Vis, fluorescence and NMR titrations as well as theoretical calculations. This studies have shown that the metal cation is indirectly affecting the emission favouring a conformation in which the fluorophore is at stacking distance from the electron poor pyridine moieties. This gives rise to an oxidative photoinduced electron transfer from the excited state of the fluorophore to the electron-poor Zn2+ coordined pyridine.
PubMed: 38940317
DOI: 10.1002/cplu.202400342 -
Open Veterinary Journal May 2024Pseudothrombocytopenia is a commonly obtained false negative result when analyzing feline platelet (PLT) count by an automated machine. It is related to ethylenediamine...
BACKGROUND
Pseudothrombocytopenia is a commonly obtained false negative result when analyzing feline platelet (PLT) count by an automated machine. It is related to ethylenediamine tetra-acetic acid (EDTA), a widely utilized anticoagulant in blood collection tubes, resulting in EDTA-dependent pseudothrombocytopenia (EDTA-PTCP).
AIM
To investigate whether treated with kanamycin enhanced the quantity of PLT aggregations in feline blood specimens collected using EDTA-PTCP.
METHODS
Thirty-one blood samples were obtained using EDTA tubes. The complete blood count was analyzed using an automated Mindray BC-5000Vet. Both Manual cell counts and thin blood smears were performed to estimate the amount of red blood cell, white blood cell, and PLTs as well as to evaluate the severity scores of PLT clumping, respectively. Comparisons were made between those pre-treated and those treated with kanamycin in the EDTA tube.
RESULTS
There were significantly different mean PLT counts in the samples before and after they were treated with kanamycin, both on automated (156.6 ± 76.4 . 260.3 ± 115.5; < 0.001) and manual (168.5 ± 92.1 . 262.8 ± 119.6; < 0.001) readings, with a 95% confidence interval of 0.19 (0.022-0.365).
CONCLUSION
This study suggests that in clinical laboratory practice, kanamycin should be added to feline blood specimens with EDTA-PTCP.
Topics: Animals; Cats; Edetic Acid; Kanamycin; Thrombocytopenia; Cat Diseases; Anticoagulants; Platelet Count; Blood Specimen Collection; Female; Male; Platelet Aggregation
PubMed: 38938430
DOI: 10.5455/OVJ.2024.v14.i5.15 -
Amino Acids Jun 2024Exogenous polyamines, including putrescine (PUT), spermidine (SPD), and spermine (SPM), and the irreversible inhibitor of the rate-limiting enzyme ornithine...
Exogenous polyamines, including putrescine (PUT), spermidine (SPD), and spermine (SPM), and the irreversible inhibitor of the rate-limiting enzyme ornithine decarboxylase (ODC) of polyamine biosynthesis, α-difluoromethylornithine (DFMO), are implicated as stimulants for bone formation. We demonstrate in this study the osteogenic potential of exogenous polyamines and DFMO in human osteoblasts (hOBs), murine monocyte cell line RAW 264.7, and an ovariectomized rat model. The effect of polyamines and DFMO on hOBs and RAW 264.7 cells was studied by analyzing gene expression, alkaline phosphatase (ALP) activity, tartrate-resistant acid phosphatase (TRAP) activity, and matrix mineralization. Ovariectomized rats were treated with polyamines and DFMO and analyzed by micro computed tomography (micro CT). The mRNA level of the early onset genes of osteogenic differentiation, Runt-related transcription factor 2 (Runx2) and ALP, was significantly elevated in hOBs under osteogenic conditions, while both ALP activity and matrix mineralization were enhanced by exogenous polyamines and DFMO. Under osteoclastogenic conditions, the gene expression of both receptor activator of nuclear factor-κB (RANK) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) was reduced, and TRAP activity was suppressed by exogenous polyamines and DFMO in RAW 264.7 cells. In an osteoporotic animal model of ovariectomized rats, SPM and DFMO were found to improve bone volume in rat femurs, while trabecular thickness was increased in all treatment groups. Results from this study provide in vitro and in vivo evidence indicating that polyamines and DFMO act as stimulants for bone formation, and their osteogenic effect may be associated with the suppression of osteoclastogenesis.
Topics: Animals; Mice; Osteoclasts; Osteogenesis; Rats; Humans; Cell Differentiation; Eflornithine; Female; Polyamines; Osteoblasts; RAW 264.7 Cells; Ovariectomy; Rats, Sprague-Dawley; Spermidine
PubMed: 38935136
DOI: 10.1007/s00726-024-03403-8 -
International Journal of Nanomedicine 2024[This retracts the article DOI: 10.2147/IJN.S160848.].
Endogenous Ornithine Decarboxylase/Polyamine System Mediated the Antagonist Role of Insulin/PEG-CMCS Preconditioning against Heart Ischemia/Reperfusion Injury in Diabetes Mellitus [Retraction].
[This retracts the article DOI: 10.2147/IJN.S160848.].
PubMed: 38933417
DOI: 10.2147/IJN.S483384 -
International Journal of Molecular... Jun 2024Our study aimed to investigate the role of ferroptosis in sevoflurane-induced hearing impairment and explore the mechanism of the microRNA-182-5p...
Our study aimed to investigate the role of ferroptosis in sevoflurane-induced hearing impairment and explore the mechanism of the microRNA-182-5p (miR-182-5p)/Glutathione Peroxidase 4 (GPX4) pathway in sevoflurane-induced ototoxicity. Immunofluorescence staining was performed using myosin 7a and CtBP2. Cell viability was assessed using the CCK-8 kit. Fe concentration was measured using FerroOrange and Mi-to-FerroGreen fluorescent probes. The lipid peroxide level was assessed using BODIPY 581/591 C11 and MitoSOX fluorescent probes. The auditory brainstem response (ABR) test was conducted to evaluate the hearing status. Bioinformatics tools and dual luciferase gene reporter analysis were used to confirm the direct targeting of miR-182-5p on GPX4 mRNA. GPX4 and miR-182-5p expression in cells was assessed by qRT-PCR and Western blot. Ferrostatin-1 (Fer-1) pretreatment significantly improved hearing impairment and damage to ribbon synapses in mice caused by sevoflurane exposure. Immunofluorescence staining revealed that Fer-1 pretreatment reduced intracellular and mitochondrial iron overload, as well as lipid peroxide accumulation. Our findings indicated that miR-182-5p was upregulated in sevoflurane-exposed HEI-OC1 cells, and miR-182-5p regulated GPX4 expression by binding to the 3'UTR of GPX4 mRNA. The inhibition of miR-182-5p attenuated sevoflurane-induced iron overload and lipid peroxide accumulation. Our study elucidated that the miR-182-5p/GPX4 pathway was implicated in sevoflurane-induced ototoxicity by promoting ferroptosis.
Topics: Ferroptosis; MicroRNAs; Sevoflurane; Phospholipid Hydroperoxide Glutathione Peroxidase; Animals; Mice; Ototoxicity; Signal Transduction; Cell Line; Male; Hearing Loss; Mice, Inbred C57BL; Phenylenediamines; Cyclohexylamines
PubMed: 38928480
DOI: 10.3390/ijms25126774 -
International Journal of Molecular... Jun 2024This study aimed to investigate the gut microbiota composition in children with autism spectrum disorder (ASD) compared to neurotypical (NT) children, with a focus on...
Comprehensive Analysis of Gut Microbiota Composition and Functional Metabolism in Children with Autism Spectrum Disorder and Neurotypical Children: Implications for Sex-Based Differences and Metabolic Dysregulation.
This study aimed to investigate the gut microbiota composition in children with autism spectrum disorder (ASD) compared to neurotypical (NT) children, with a focus on identifying potential differences in gut bacteria between these groups. The microbiota was analyzed through the massive sequencing of region V3-V4 of the 16S RNA gene, utilizing DNA extracted from stool samples of participants. Our findings revealed no significant differences in the dominant bacterial phyla (Firmicutes, Bacteroidota, Actinobacteria, Proteobacteria, Verrucomicrobiota) between the ASD and NT groups. However, at the genus level, notable disparities were observed in the abundance of , , , and , all of which have been previously associated with ASD. Furthermore, a sex-based analysis unveiled additional discrepancies in gut microbiota composition. Specifically, three genera (, , ) exhibited variations between male and female groups in both ASD and NT cohorts. Particularly noteworthy was the exclusive presence of in females with ASD. Analysis of predicted metabolic pathways suggested an enrichment of pathways related to amine and polyamine degradation, as well as amino acid degradation in the ASD group. Conversely, pathways implicated in carbohydrate biosynthesis, degradation, and fermentation were found to be underrepresented. Despite the limitations of our study, including a relatively small sample size (30 ASD and 31 NT children) and the utilization of predicted metabolic pathways derived from 16S RNA gene analysis rather than metagenome sequencing, our findings contribute to the growing body of evidence suggesting a potential association between gut microbiota composition and ASD. Future research endeavors should focus on validating these findings with larger sample sizes and exploring the functional significance of these microbial differences in ASD. Additionally, there is a critical need for further investigations to elucidate sex differences in gut microbiota composition and their potential implications for ASD pathology and treatment.
Topics: Humans; Gastrointestinal Microbiome; Autism Spectrum Disorder; Female; Male; Child; RNA, Ribosomal, 16S; Bacteria; Feces; Child, Preschool; Sex Factors; Sex Characteristics; Metabolic Networks and Pathways
PubMed: 38928411
DOI: 10.3390/ijms25126701