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Toxics Jun 2024The associations between VOCs and sex hormones in adolescents remain unclear, and the role of serum albumin in these associations deserves to be explored. We conducted...
The associations between VOCs and sex hormones in adolescents remain unclear, and the role of serum albumin in these associations deserves to be explored. We conducted cross-sectional analyses using generalized linear models (GLMs), weighted quantile sum (WQS) regression, and mediation analysis, based on data from 584 adolescents from the National Health and Nutrition Examination Survey (NHANES). The GLM analyses revealed that seven kinds of mVOCs potentially affected sex hormone levels. According to the WQS regression results, 2-aminothiazoline-4-carboxylic acid (ATCA) was the major contributor to the significant associations of mixed mVOC exposure with testosterone, estradiol, and free androgen index in males; N-acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCC) was the major contributor to the significant associations of mixed mVOC exposure with sex hormone-binding globulin in males; and N-acetyl-S-(benzyl)-L-cysteine (BMA) was the major contributor to the significant associations of mixed mVOC exposure with the ratio of testosterone to estradiol in females. Moreover, serum albumin could mediate up to 9.2% of the associations between mixed exposure to mVOCs and sex hormones. Our findings could provide a reference for studies on the mechanisms underlying the effects of VOCs on sex hormones in adolescents and emphasize the necessity of reducing exposure to ATCA, AMCC, BMA, and their parent compounds.
PubMed: 38922118
DOI: 10.3390/toxics12060438 -
Marine Drugs Jun 2024To promote the bioconversion of marine chitin waste into value-added products, we expressed a novel pH-stable -derived chitinase, Chi1, in and subsequently purified,...
To promote the bioconversion of marine chitin waste into value-added products, we expressed a novel pH-stable -derived chitinase, Chi1, in and subsequently purified, characterized, and evaluated it for its chitin-converting capacity. Our results indicated that Chi1 is of the glycoside hydrolase (GH) family 18 with a molecular weight of approximately 57 kDa, consisting of a GH18 catalytic domain and a cellulose-binding domain. We recorded its optimal activity at pH 5.0 and 55 °C. It exhibited excellent stability in a wide pH range of 3.0-10.0. Mg (5 mM), and dithiothreitol (10 mM) significantly promoted Chi1 activity. Chi1 exhibited broad substrate specificity and hydrolyzed chitin, chitosan, cellulose, soluble starch, and -acetyl chitooligosaccharides with polymerization degrees ranging from three to six. Moreover, Chi1 exhibited an endo-type cleavage pattern, and it could efficiently convert colloidal chitin into -acetyl-D-glucosamine (GlcNAc) and (GlcNAc) with yields of 227.2 and 505.9 mg/g chitin, respectively. Its high chitin-degrading capacity and exceptional pH tolerance makes it a promising tool with potential applications in chitin waste treatment and bioactive oligosaccharide production.
Topics: Chitinases; Chitin; Hydrogen-Ion Concentration; Substrate Specificity; Micromonospora; Hydrolysis; Escherichia coli; Chitosan; Enzyme Stability
PubMed: 38921598
DOI: 10.3390/md22060287 -
Marine Drugs Jun 2024, a filamentous fungus widely distributed across terrestrial and marine environments, can produce a diverse array of natural products, including alkaloids, polyketones,...
, a filamentous fungus widely distributed across terrestrial and marine environments, can produce a diverse array of natural products, including alkaloids, polyketones, and polyketide-terpenoids. Among these, chrodrimanins represented a typical class of natural products. In this study, we isolated three previously undescribed pentaketide-sesquiterpenes, 8,9--chrodrimanins (-), along with eight known compounds (-). The structures of compounds - were elucidated using nuclear magnetic resonance (NMR) and mass spectrometry (MS), while their absolute configurations were determined through X-ray crystallography and electronic circular dichroism (ECD) computations. The biosynthetic pathways of compounds - initiate with 6-hydroxymellein and involve multiple stages of isoprenylation, cyclization, oxidation, and acetylation. We selected four strains of gastrointestinal cancer cells for activity evaluation. We found that compound selectively inhibited MKN-45, whereas compounds and exhibited no significant inhibitory activity against the four cell lines. These findings suggested that 8,9--chrodrimanins could serve as scaffold compounds for further structural modifications, potentially leading to the development of targeted therapies for gastric cancer.
Topics: Talaromyces; Humans; Cell Line, Tumor; Antineoplastic Agents; Crystallography, X-Ray; Biological Products; Aquatic Organisms; Magnetic Resonance Spectroscopy; Polyketides; Molecular Structure
PubMed: 38921585
DOI: 10.3390/md22060274 -
Metabolites Jun 2024Acetate is an important metabolite in metabolic fluxes. Its presence in biological entities originates from both exogenous inputs and endogenous metabolism. Because the...
Acetate is an important metabolite in metabolic fluxes. Its presence in biological entities originates from both exogenous inputs and endogenous metabolism. Because the change in blood acetate level has been associated with both beneficial and adverse health outcomes, blood acetate analysis has been used to monitor the systemic status of acetate turnover. The present study examined the use of urinary -acetyltaurine (NAT) as a marker to reflect the hyperacetatemic status of mice from exogenous inputs and endogenous metabolism, including triacetin dosing, ethanol dosing, and streptozotocin-induced diabetes. The results showed that triacetin dosing increased serum acetate and urinary NAT but not other -acetylated amino acids in urine. The co-occurrences of increased serum acetate and elevated urinary NAT were also observed in both ethanol dosing and streptozotocin-induced diabetes. Furthermore, the renal cortex was determined as an active site for NAT synthesis. Overall, urinary NAT behaved as an effective marker of hyperacetatemia in three experimental mouse models, warranting further investigation into its application in humans.
PubMed: 38921457
DOI: 10.3390/metabo14060322 -
Journal of Fungi (Basel, Switzerland) May 2024The acetylation of histone lysine residues regulates multiple life processes, including growth, conidiation, and pathogenicity in filamentous pathogenic fungi. However,...
The acetylation of histone lysine residues regulates multiple life processes, including growth, conidiation, and pathogenicity in filamentous pathogenic fungi. However, the specific function of each lysine residue at the N-terminus of histone H3 in phytopathogenic fungi remains unclear. In this study, we mutated the N-terminal lysine residues of histone H3 in , the main causal agent of Fusarium crown rot of wheat in China, which also produces deoxynivalenol (DON) toxins harmful to humans and animals. Our findings reveal that all the FpH3, FpH3, FpH3, and FpH3 mutants are vital for vegetative growth and conidiation. Additionally, FpH3K14 regulates the pathogen's sensitivity to various stresses and fungicides. Despite the slowed growth of the FpH3 and FpH3 mutants, their pathogenicity towards wheat stems and heads remains unchanged. However, the FpH3 mutant produces more DON. Furthermore, the FpH3 and FpH3 mutants exhibit significantly reduced virulence, with the FpH3 mutant producing minimal DON. In the FpH3, FpH3, FpH3, and FpH3 mutants, there are 1863, 1400, 1688, and 1806 downregulated genes, respectively, compared to the wild type. These downregulated genes include many that are crucial for growth, conidiation, pathogenicity, and DON production, as well as some essential genes. Gene ontology (GO) enrichment analysis indicates that genes downregulated in the FpH3 and FpH3 mutants are enriched for ribosome biogenesis, rRNA processing, and rRNA metabolic process. This suggests that the translation machinery is abnormal in the FpH3 and FpH3 mutants. Overall, our findings suggest that H3 N-terminal lysine residues are involved in regulating the expression of genes with important functions and are critical for fungal development and pathogenicity.
PubMed: 38921366
DOI: 10.3390/jof10060379 -
Nano Letters Jun 2024Osseointegration is the most important factor determining implant success. The surface modification of TiO nanotubes prepared by anodic oxidation has remarkable...
Osseointegration is the most important factor determining implant success. The surface modification of TiO nanotubes prepared by anodic oxidation has remarkable advantages in promoting bone formation. However, the mechanism behind this phenomenon is still unintelligible. Here we show that the nanomorphology exhibited open and clean nanotube structure and strong hydrophilicity, and the nanomorphology significantly facilitated the adhesion, proliferation, and osteogenesis differentiation of stem cells. Exploring the mechanism, we found that the nanomorphology can enhance mitochondrial oxidative phosphorylation (OxPhos) by activating Piezo1 and increasing intracellular Ca. The increase in OxPhos can significantly uplift the level of acetyl-CoA in the cytoplasm but not significantly raise the level of acetyl-CoA in the nucleus, which was beneficial for the acetylation and stability of β-catenin and ultimately promoted osteogenesis. This study provides a new interpretation for the regulatory mechanism of stem cell osteogenesis by nanomorphology.
PubMed: 38920296
DOI: 10.1021/acs.nanolett.4c01101 -
Open Biology Jun 2024is the predominant mould pathogen for humans. Adaption to host-imposed iron limitation has previously been demonstrated to be essential for its virulence. [2Fe-2S]...
is the predominant mould pathogen for humans. Adaption to host-imposed iron limitation has previously been demonstrated to be essential for its virulence. [2Fe-2S] clusters are crucial as cofactors of several metabolic pathways and mediate cytosolic/nuclear iron sensing in fungi including . [2Fe-2S] cluster trafficking has been shown to involve BolA family proteins in both mitochondria and the cytosol/nucleus. Interestingly, both homologues, termed Bol1 and Bol3, possess mitochondrial targeting sequences, suggesting the lack of cytosolic/nuclear versions. Here, we show by the combination of mutational, proteomic and fluorescence microscopic analyses that expression of the Bol3 encoding gene leads to dual localization of gene products to mitochondria and the cytosol/nucleus via alternative translation initiation downstream of the mitochondrial targeting sequence, which appears to be highly conserved in various species. Lack of either mitochondrial Bol1 or Bol3 was phenotypically inconspicuous while lack of cytosolic/nuclear Bol3 impaired growth during iron limitation but not iron sensing which indicates a particular importance of [2Fe-2S] cluster trafficking during iron limitation. Remarkably, cytosolic/nuclear Bol3 differs from the mitochondrial version only by N-terminal acetylation, a finding that was only possible by mutational hypothesis testing.
Topics: Aspergillus fumigatus; Fungal Proteins; Cytosol; Mitochondria; Iron; Adaptation, Physiological; Cell Nucleus; Protein Transport; Proteomics; Iron-Sulfur Proteins; Gene Expression Regulation, Fungal; Acetylation
PubMed: 38919062
DOI: 10.1098/rsob.240033 -
Journal of Translational Medicine Jun 2024Sorafenib resistance is becoming increasingly common and disadvantageous for hepatocellular carcinoma (HCC) treatment. Ferroptosis is an iron dependent programmed cell...
BACKGROUND
Sorafenib resistance is becoming increasingly common and disadvantageous for hepatocellular carcinoma (HCC) treatment. Ferroptosis is an iron dependent programmed cell death underlying the mechanism of sorafenib. Iron is crucial for synthesis of cofactors essential to mitochondrial enzymes and necessary for HCC proliferation, while mitochondrial iron overload and oxidative stress are associated with sorafenib induced ferroptosis. However, the crosstalk among iron homeostasis and sorafenib resistance is unclear.
METHODS
We conducted bioinformatics analysis of sorafenib treated HCC datasets to analyze GCN5L1 and iron related gene expression with sorafenib resistance. GCN5L1 deleted HCC cell lines were generated by CRISPR technology. Sorafenib resistant HCC cell line was established to validate dataset analysis and evaluate the effect of potential target.
RESULTS
We identified GCN5L1, a regulator of mitochondrial acetylation, as a modulator in sorafenib-induced ferroptosis via affecting mitochondrial iron homeostasis. GCN5L1 deficiency significantly increased sorafenib sensitivity in HCC cells by down-regulating mitochondrial iron transporters CISD1 expression to induce iron accumulation. Mitochondrial iron accumulation leads to an acceleration in cellular and lipid ROS. Sorafenib resistance is related to CISD1 overexpression to release mitochondrial iron and maintaining mitochondrial homeostasis. We combined CISD1 inhibitor NL-1 with sorafenib, which significantly enhanced sorafenib-induced ferroptosis by promoting mitochondrial iron accumulation and lipid peroxidation. The combination of NL-1 with sorafenib enhanced sorafenib efficacy in vitro and in vivo.
CONCLUSIONS
Our findings demonstrate that GCN5L1/CISD1 axis is crucial for sorafenib resistance and would be a potential therapeutic strategy for sorafenib resistant HCC.
Topics: Sorafenib; Carcinoma, Hepatocellular; Liver Neoplasms; Iron; Humans; Homeostasis; Mitochondria; Cell Line, Tumor; Animals; Ferroptosis; Drug Resistance, Neoplasm; Mice, Nude; Reactive Oxygen Species; Mice; Gene Expression Regulation, Neoplastic
PubMed: 38918793
DOI: 10.1186/s12967-024-05404-3 -
Biomedical Engineering Online Jun 2024Diabetic retinopathy (DR) is an eye disease that causes blindness and vision loss in diabetic. Risk factors for DR include high blood glucose levels and some... (Review)
Review
Diabetic retinopathy (DR) is an eye disease that causes blindness and vision loss in diabetic. Risk factors for DR include high blood glucose levels and some environmental factors. The pathogenesis is based on inflammation caused by interferon and other nuclear proteins. This review article provides an overview of DR and discusses the role of nuclear proteins in the pathogenesis of the disease. Some core proteins such as MAPK, transcription co-factors, transcription co-activators, and others are part of this review. In addition, some current advanced treatment resulting from the role of nuclear proteins will be analyzes, including epigenetic modifications, the use of methylation, acetylation, and histone modifications. Stem cell technology and the use of nanobiotechnology are proposed as promising approaches for a more effective treatment of DR.
Topics: Diabetic Retinopathy; Humans; Nuclear Proteins; Animals; Epigenesis, Genetic
PubMed: 38918766
DOI: 10.1186/s12938-024-01258-4 -
Scientific Reports Jun 2024Due to its involvement in physiological and pathological processes, histone deacetylase 6 (HDAC6) is considered a promising pharmaceutical target for several...
Due to its involvement in physiological and pathological processes, histone deacetylase 6 (HDAC6) is considered a promising pharmaceutical target for several neurological manifestations. However, the exact regulatory role of HDAC6 in the central nervous system (CNS) is still not fully understood. Hence, using a semi-automated literature screening technique, we systematically collected HDAC6-protein interactions that are experimentally validated and reported in the CNS. The resulting HDAC6 network encompassed 115 HDAC6-protein interactions divided over five subnetworks: (de)acetylation, phosphorylation, protein complexes, regulatory, and aggresome-autophagy subnetworks. In addition, 132 indirect interactions identified through HDAC6 inhibition were collected and categorized. Finally, to display the application of our HDAC6 network, we mapped transcriptomics data of Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis on the network and highlighted that in the case of Alzheimer's disease, alterations predominantly affect the HDAC6 phosphorylation subnetwork, whereas differential expression within the deacetylation subnetwork is observed across all three neurological disorders. In conclusion, the HDAC6 network created in the present study is a novel and valuable resource for the understanding of the HDAC6 regulatory mechanisms, thereby providing a framework for the integration and interpretation of omics data from neurological disorders and pharmacodynamic assessments.
Topics: Histone Deacetylase 6; Humans; Protein Interaction Maps; Nervous System Diseases; Alzheimer Disease; Phosphorylation; Acetylation; Parkinson Disease
PubMed: 38918466
DOI: 10.1038/s41598-024-65094-1