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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 -
International Journal of Molecular... Jun 2024Water deficit affects the growth as well as physiological and biochemical processes in plants. The aim of this study was to determine differences in physiological and...
Water deficit affects the growth as well as physiological and biochemical processes in plants. The aim of this study was to determine differences in physiological and biochemical responses to drought stress in two wheat cultivars-Chinese Spring (CS) and SQ1 (which are parents of a mapping population of doubled haploid lines)-and to relate these responses to final yield and agronomic traits. Drought stress was induced by withholding water for 14 days, after which plants were re-watered and maintained until harvest. Instantaneous gas exchange parameters were evaluated on the 3rd, 5th, 10th, and 14th days of seedling growth under drought. After 14 days, water content and levels of chlorophyll +, carotenoids, malondialdehyde, soluble carbohydrates, phenolics, salicylic acid, abscisic acid (ABA), and polyamines were measured. At final maturity, yield components (grain number and weight), biomass, straw weight, and harvest index were evaluated. Physiological and biochemical parameters of CS responded more than those of SQ1 to the 14-day drought, reflected in a greater reduction in final biomass and yield in CS. Marked biochemical differences between responses of CS and SQ1 to the drought were found for soluble carbohydrates and polyamines. These would be good candidates for testing in the mapping population for the coincidence of the genetic control of these traits and final biomass and yield.
Topics: Triticum; Droughts; Stress, Physiological; Chlorophyll; Water; Chromosome Mapping; Biomass; Abscisic Acid; Seedlings
PubMed: 38928284
DOI: 10.3390/ijms25126573 -
International Journal of Molecular... Jun 2024Polyamine (PA) spermidine (SPD) plays a crucial role in aging. Since SPD accumulates in glial cells, particularly in Müller retinal cells (MCs), the expression of the...
Polyamine (PA) spermidine (SPD) plays a crucial role in aging. Since SPD accumulates in glial cells, particularly in Müller retinal cells (MCs), the expression of the SPD-synthesizing enzyme spermidine synthase (SpdS) in Müller glia and age-dependent SpdS activity are not known. We used immunocytochemistry, Western blot (WB), and image analysis on rat retinae at postnatal days 3, 21, and 120. The anti-glutamine synthetase (GS) antibody was used to identify glial cells. In the neonatal retina (postnatal day 3 (P3)), SpdS was expressed in almost all progenitor cells in the neuroblast. However, by day 21 (P21), the SpdS label was pronouncedly expressed in multiple neurons, while GS labels were observed only in radial Müller glial cells. During early cell adulthood, at postnatal day 120 (P120), SpdS was observed solely in ganglion cells and a few other neurons. Western blot and semi-quantitative analyses of SpdS labeling showed a dramatic decrease in SpdS at P21 and P120 compared to P3. In conclusion, the redistribution of SpdS with aging indicates that SPD is first synthesized in all progenitor cells and then later in neurons, but not in glia. However, MCs take up and accumulate SPD, regardless of the age-associated decrease in SPD synthesis in neurons.
Topics: Animals; Rats; Spermidine Synthase; Retina; Ependymoglial Cells; Aging; Spermidine; Neuroglia; Animals, Newborn
PubMed: 38928162
DOI: 10.3390/ijms25126458 -
International Journal of Molecular... Jun 2024Polyamines are ubiquitous in almost all biological entities and involved in various crucial physiological processes. They are also closely associated with the onset and... (Review)
Review
Polyamines are ubiquitous in almost all biological entities and involved in various crucial physiological processes. They are also closely associated with the onset and progression of many diseases. Polyaminopathies are a group of rare genetic disorders caused by alterations in the function of proteins within the polyamine metabolism network. Although the identified polyaminopathies are all rare diseases at present, they are genetically heritable, rendering high risks not only to the carriers but also to their descendants. Meanwhile, more polyaminopathic patients might be discovered with the increasing accessibility of gene sequencing. This review aims to provide a comprehensive overview of the structural variations of mutated proteins in current polyaminopathies, in addition to their causative genes, types of mutations, clinical symptoms, and therapeutic approaches. We focus on analyzing how alterations in protein structure lead to protein dysfunction, thereby facilitating the onset of diseases. We hope this review will offer valuable insights and references for the future clinical diagnosis and precision treatment of polyaminopathies.
Topics: Humans; Polyamines; Mutation; Animals
PubMed: 38928047
DOI: 10.3390/ijms25126340 -
Scientific Reports Jun 2024Adipose-derived stem cells (ADSCs) are promising in regenerative medicine. Their proliferation, survival and activation are influenced by specific signals within their...
Adipose-derived stem cells (ADSCs) are promising in regenerative medicine. Their proliferation, survival and activation are influenced by specific signals within their microenvironment, also known as niche. The stem cell niche is regulated by complex interactions between multiple cell types. When transplanted in a specific area, ADSCs can secrete several immunomodulatory factors. At the same time, a tumor microenvironment can influence stem cell behavior, modulating proliferation and their ability to differentiate into a specific phenotype. Whitin this context, we exposed ADSCs to plasma samples derived from human patients diagnosed with prostate cancer (PC), or precancerous lesions (PL), or benign prostatic hyperplasia (BPH) for 4, 7 or 10 days. We then analyzed the expression of main stemness-related markers and cell-cycle regulators. We also measured cytokine production and polyamine secretion in culture medium and evaluated cell morphology and collagen production by confocal microscopy. The results obtained from this study show significant changes in the morphology of ADSCs exposed to plasma samples, especially in the presence of prostate cancer plasma, suggesting important implications in the use of ADSCs for the development of new treatments and application in regenerative medicine.
Topics: Male; Humans; Prostatic Neoplasms; Prostatic Hyperplasia; Stem Cells; Adipose Tissue; Prostate; Cell Differentiation; Cell Proliferation; Cytokines; Cells, Cultured; Aged; Middle Aged
PubMed: 38926454
DOI: 10.1038/s41598-024-64625-0 -
Journal of Cellular and Molecular... Jun 2024We aimed to explore whether the genes associated with both platinum-based therapy and polyamine metabolism could predict the prognosis of LUAD. We searched for the...
We aimed to explore whether the genes associated with both platinum-based therapy and polyamine metabolism could predict the prognosis of LUAD. We searched for the differential expression genes (DEGs) associated with platinum-based therapy, then we interacted them with polyamine metabolism-related genes to obtain hub genes. Subsequently, we analysed the main immune cell populations in LUAD using the scRNA-seq data, and evaluated the activity of polyamine metabolism of different cell subpopulations. The DEGs between high and low activity groups were screened to identify key DEGs to establish prognostic risk score model. We further elucidated the landscape of immune cells, mutation and drug sensitivity analysis in different risk groups. Finally, we got 10 hub genes associated with both platinum-based chemotherapy and polyamine metabolism, and found that these hub genes mainly affected signalling transduction pathways. B cells and mast cells with highest polyamine metabolism activity, while NK cells were found with lowest polyamine metabolism activity based on scRNA-seq data. DEGs between high and low polyamine metabolism activity groups were identified, then 6 key genes were screened out to build risk score, which showed a good predictive power. The risk score showed a universal negative correlation with immunotherapy checkpoint genes and the cytotoxic T cells infiltration. The mutation rates of EGFR in low-risk group was significantly higher than that of high-risk group. In conclusion, we developed a risk score based on key genes associated with platinum-based therapy and polyamine metabolism, which provide a new perspective for prognosis prediction of LUAD.
Topics: Humans; Polyamines; Prognosis; Adenocarcinoma of Lung; Gene Expression Regulation, Neoplastic; Lung Neoplasms; Mutation; Gene Expression Profiling; Biomarkers, Tumor
PubMed: 38924680
DOI: 10.1111/jcmm.18387 -
PloS One 2024This study investigated the mitigating effects of spermidine on salinity-stressed yarrow plants (Achillea millefolium L.), an economically important medicinal crop....
This study investigated the mitigating effects of spermidine on salinity-stressed yarrow plants (Achillea millefolium L.), an economically important medicinal crop. Plants were treated with four salinity levels (0, 30, 60, 90 mM NaCl) and three spermidine concentrations (0, 1.5, 3 μM). Salinity induced electrolyte leakage in a dose-dependent manner, increasing from 22% at 30 mM to 56% at 90 mM NaCl without spermidine. However, 1.5 μM spermidine significantly reduced leakage across salinities by 1.35-11.2% relative to untreated stressed plants. Photosynthetic pigments (chlorophyll a, b, carotenoids) also exhibited salinity- and spermidine-modulated responses. While salinity decreased chlorophyll a, both spermidine concentrations increased chlorophyll b and carotenoids under most saline conditions. Salinity and spermidine synergistically elevated osmoprotectants proline and total carbohydrates, with 3 μM spermidine augmenting proline and carbohydrates up to 14.4% and 13.1% at 90 mM NaCl, respectively. Antioxidant enzymes CAT, POD and APX displayed complex regulation influenced by treatment factors. Moreover, salinity stress and spermidine also influenced the expression of linalool and pinene synthetase genes, with the highest expression levels observed under 90 mM salt stress and the application of 3 μM spermidine. The findings provide valuable insights into the responses of yarrow plants to salinity stress and highlight the potential of spermidine in mitigating the adverse effects of salinity stress.
Topics: Spermidine; Achillea; Salt Stress; Chlorophyll; Photosynthesis; Carotenoids; Proline; Gene Expression Regulation, Plant; Salinity; Antioxidants; Sodium Chloride; Chlorophyll A
PubMed: 38923971
DOI: 10.1371/journal.pone.0304831 -
Tropical Medicine and Infectious Disease Jun 2024L-arginine metabolism is strongly linked with immunity to mycobacteria, primarily through the antimicrobial activity of nitric oxide (NO). The potential to modulate...
Therapeutic Modulation of Arginase with nor-NOHA Alters Immune Responses in Experimental Mouse Models of Pulmonary Tuberculosis including in the Setting of Human Immunodeficiency Virus (HIV) Co-Infection.
L-arginine metabolism is strongly linked with immunity to mycobacteria, primarily through the antimicrobial activity of nitric oxide (NO). The potential to modulate tuberculosis (TB) outcomes through interventions that target L-arginine pathways are limited by an incomplete understanding of mechanisms and inadequate in vivo modeling. These gaps in knowledge are compounded for HIV and Mtb co-infections, where activation of arginase-1 due to HIV infection may promote survival and replication of both Mtb and HIV. We utilized in vitro and in vivo systems to determine how arginase inhibition using N-hydroxy-nor-L-arginine (nor-NOHA) alters L-arginine pathway metabolism relative to immune responses and disease outcomes following Mtb infection. Treatment with nor-NOHA polarized murine macrophages (RAW 264.7) towards M1 phenotype, increased NO, and reduced Mtb in RAW macrophages. In Balb/c mice, nor-NOHA reduced pulmonary arginase and increased the antimicrobial metabolite spermine in association with a trend towards reduced Mtb CFU in lung. In humanized immune system (HIS) mice, HIV infection increased plasma arginase and heightened the pulmonary arginase response to Mtb. Treatment with nor-NOHA increased cytokine responses to Mtb and Mtb/HIV in lung tissue but did not significantly alter bacterial burden or viral load. Our results suggest that L-arginine pathway modulators may have potential as host-directed therapies to augment antibiotics in TB chemotherapy.
PubMed: 38922041
DOI: 10.3390/tropicalmed9060129 -
Cells Jun 2024Hepatitis C virus (HCV) is an oncogenic virus that causes chronic liver disease in more than 80% of patients. During the last decade, efficient direct-acting antivirals...
Hepatitis C virus (HCV) is an oncogenic virus that causes chronic liver disease in more than 80% of patients. During the last decade, efficient direct-acting antivirals were introduced into clinical practice. However, clearance of the virus does not reduce the risk of end-stage liver diseases to the level observed in patients who have never been infected. So, investigation of HCV pathogenesis is still warranted. Virus-induced changes in cell metabolism contribute to the development of HCV-associated liver pathologies. Here, we studied the impact of the virus on the metabolism of polyamines and proline as well as on the urea cycle, which plays a crucial role in liver function. It was found that HCV strongly suppresses the expression of arginase, a key enzyme of the urea cycle, leading to the accumulation of arginine, and up-regulates proline oxidase with a concomitant decrease in proline concentrations. The addition of exogenous proline moderately suppressed viral replication. HCV up-regulated transcription but suppressed protein levels of polyamine-metabolizing enzymes. This resulted in a decrease in polyamine content in infected cells. Finally, compounds targeting polyamine metabolism demonstrated pronounced antiviral activity, pointing to spermine and spermidine as compounds affecting HCV replication. These data expand our understanding of HCV's imprint on cell metabolism.
Topics: Proline; Humans; Hepacivirus; Polyamines; Urea; Virus Replication; Arginase; Antiviral Agents; Hepatitis C; Cell Line, Tumor; Proline Oxidase
PubMed: 38920664
DOI: 10.3390/cells13121036