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Scientific Reports Sep 2023Biological properties of protein molecules depend on their interaction with other molecules, and enzymes are no exception. Enzyme activities are controlled by their...
Biological properties of protein molecules depend on their interaction with other molecules, and enzymes are no exception. Enzyme activities are controlled by their interaction with other molecules in living cells. Enzyme activation and their catalytic properties in the presence of different types of polymers have been studied in vitro, although these studies are restricted to only a few enzymes. In this study, we show that addition of poly-l-lysine (PLL) can increase the enzymatic activity of multiple oxidoreductases through formation of enzyme assemblies. Oxidoreductases with an overall negative charge, such as l-lactate oxidase, d-lactate dehydrogenase, pyruvate oxidase, and acetaldehyde dehydrogenase, each formed assemblies with the positively charged PLL via electrostatic interactions. The enzyme activities of these oxidoreductases in the enzyme assemblies were several-folds higher than those of the enzyme in their natural dispersed state. In the presence of PLL, the turnover number (k) improved for all enzymes, whereas the decrease in Michaelis constant (K) was enzyme dependent. This type of enzyme function regulation through the formation of assemblies via simple addition of polymers has potential for diverse applications, including various industrial and research purposes.
Topics: L-Lactate Dehydrogenase; Catalysis; Industry; Lysine; Poly A; Polymers
PubMed: 37658129
DOI: 10.1038/s41598-023-41789-9 -
Respiratory Research Apr 2024Environmental/occupational exposures cause significant lung diseases. Agricultural organic dust extracts (ODE) and bacterial component lipopolysaccharide (LPS) induce...
BACKGROUND
Environmental/occupational exposures cause significant lung diseases. Agricultural organic dust extracts (ODE) and bacterial component lipopolysaccharide (LPS) induce recruited, transitioning murine lung monocytes/macrophages, yet their cellular role remains unclear.
METHODS
CCR2 RFP mice were intratracheally instilled with high concentration ODE (25%), LPS (10 μg), or gram-positive peptidoglycan (PGN, 100 μg) for monocyte/macrophage cell-trafficking studies. CCR2 knockout (KO) mice and administration of intravenous clodronate liposomes strategies were employed to reduce circulating monocytes available for lung recruitment following LPS exposure. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected. Pro-inflammatory and/or pro-fibrotic cytokines, chemokines, and lung extracellular matrix mediators were quantitated by ELISA. Infiltrating lung cells including monocyte/macrophage subpopulations, neutrophils, and lymphocytes were characterized by flow cytometry. Lung histopathology, collagen content, vimentin, and post-translational protein citrullination and malondialdehyde acetaldehyde (MAA) modification were quantitated. Parametric statistical tests (one-way ANOVA, Tukey'smultiple comparison) and nonparametric statistical (Kruskal-Wallis, Dunn's multiple comparison) tests were used following Shapiro-Wilk testing for normality.
RESULTS
Intratracheal instillation of ODE, LPS, or PGN robustly induced the recruitment of inflammatory CCR2 CD11cCD11b monocytes/macrophages and both CCR2 and CCR2 CD11cCD11b monocytes at 48 h. There were also increases in CCR2 CD4 and CD8 T cells and NK cells. Despite reductions in LPS-induced lung infiltrating CD11cCD11b cells (54% reduction), CCR2 knockout (KO) mice were not protected against LPS-induced inflammatory and pro-fibrotic consequences. Instead, compensatory increases in lung neutrophils and CCL2 and CCL7 release occurred. In contrast, the depletion of circulating monocytes through the administration of intravenous clodronate (vs. vehicle) liposomes 24 h prior to LPS exposure reduced LPS-induced infiltrating CD11cCD11b monocyte-macrophage subpopulation by 59% without compensatory changes in other cell populations. Clodronate liposome pre-treatment significantly reduced LPS-induced IL-6 (66% reduction), matrix metalloproteinases (MMP)-3 (36%), MMP-8 (57%), tissue inhibitor of metalloproteinases (61%), fibronectin (38%), collagen content (22%), and vimentin (40%). LPS-induced lung protein citrullination and MAA modification, post-translational modifications implicated in lung disease, were reduced (39% and 48%) with clodronate vs. vehicle liposome.
CONCLUSION
Highly concentrated environmental/occupational exposures induced the recruitment of CCR2 and CCR2 transitioning monocyte-macrophage and monocyte subpopulations and targeting peripheral monocytes may reduce the adverse lung consequences resulting from exposures to LPS-enriched inhalants.
Topics: Mice; Animals; Monocytes; Liposomes; Vimentin; Lipopolysaccharides; Clodronic Acid; CD8-Positive T-Lymphocytes; Lung; Macrophages; Lung Diseases; Environmental Exposure; Collagen; Mice, Inbred C57BL
PubMed: 38594676
DOI: 10.1186/s12931-024-02804-3 -
RMD Open Dec 2023In rheumatoid arthritis (RA) around two-thirds of patients are autoantibody positive for rheumatoid factor, anti-citrullinated protein antibodies and/or...
Antibodies against advanced glycation end-products and malondialdehyde-acetaldehyde adducts identify a new specific subgroup of hitherto patients with seronegative arthritis with a distinct clinical phenotype and an HLA class II association.
OBJECTIVE
In rheumatoid arthritis (RA) around two-thirds of patients are autoantibody positive for rheumatoid factor, anti-citrullinated protein antibodies and/or anti-carbamylated protein antibodies. The remaining seronegative subgroup of patients is clinically heterogeneous and thus far, biomarkers predicting the disease course are lacking. Therefore, we analysed the value of other autoantibodies in RA directed against malondialdehyde-acetaldehyde adducts (MAA) and advanced glycation end-products (AGE).
METHODS
In sera of 648 patients with RA and 538 patients without RA from the Leiden Early Arthritis Clinic, anti-MAA and anti-AGE IgG antibody levels were measured using ELISA. Associations between genetic risk factors, acute phase reactants, radiological joint damage, remission and anti-PTM positivity were investigated using regression, correlation and survival analyses.
RESULTS
Anti-AGE and anti-MAA were most prevalent in RA (44.6% and 46.1% respectively) but were also present in non-RA arthritis patients (32.9% and 30.3% respectively). Anti-AGE and anti-MAA antibodies were associated with HLA-DRB1*03 within seronegative RA (OR=1.98, p=0.003, and OR=2.37, p<0.001, respectively) and, for anti-AGE also in non-RA arthritis patients (OR=2.34, p<0.001). Presence of anti-MAA antibodies was associated significantly with markers of inflammation, erythrocyte sedimentation rate and C reactive protein, in all groups independent of anti-AGE. Interestingly, the presence of anti-AGE and anti-MAA antibodies was associated with radiological progression in patients with seronegative RA, but not evidently with sustained drug-free remission.
CONCLUSIONS
Anti-AGE and anti-MAA were present in around 45% of RA patients and 30% of non-RA arthritis patients, and although not specific for RA, their presence associated with HLA, inflammation and, for RA, with clinical outcomes especially in patients with seronegative RA.
Topics: Humans; Acetaldehyde; Malondialdehyde; Maillard Reaction; Arthritis, Rheumatoid; Autoantibodies; Phenotype; Inflammation
PubMed: 38053459
DOI: 10.1136/rmdopen-2023-003480 -
Radiology Case Reports Sep 2023Autoimmune Hepatitis (AIH) is a progressive form of chronic hepatitis, with periods of remissions and exacerbations. Diagnosis includes abnormally high levels of...
Autoimmune Hepatitis (AIH) is a progressive form of chronic hepatitis, with periods of remissions and exacerbations. Diagnosis includes abnormally high levels of immunoglobulins and multiple autoantibodies. Clinical presentation is variable, with a spectrum extending from asymptomatic cases to fulminant liver failure. Symptoms include abdominal pain, malaise, fatigue, and small joint arthralgia. We present a case of a 36-year-old male with a past medical history of alcohol dependence and acute pancreatitis who was diagnosed with AIH. There is limited data regarding patients with concomitant AIH and pancreatitis. Our patient presented with AIH with secondary acute on chronic pancreatitis, in the absence of additional autoimmune manifestations. The mechanism of AIH remains poorly understood; however, there is an association between the HLA gene and AIH. Genetic studies have shown HLA-DRB1*0301 and HLA-DRB1*0401 as primary and secondary genotypes susceptible to AIH, as well as genetic variants with CARD10 and SH2B3. Products secondary to metabolism of ETOH such as alcohol dehydrogenase, malondialdehyde, and acetaldehyde, can lead to development of autoantibodies. Additional research is indicated to evaluate the relationship between AIH and acute pancreatitis.
PubMed: 37359250
DOI: 10.1016/j.radcr.2023.05.040 -
International Journal of Molecular... Sep 2023Polyunsaturated fatty acids (PUFAs) undergo lipid peroxidation and conversion into malondialdehyde (MDA). MDA reacts with acetaldehyde to form malondialdehyde-modified...
Lipid Peroxidation of the Docosahexaenoic Acid/Arachidonic Acid Ratio Relating to the Social Behaviors of Individuals with Autism Spectrum Disorder: The Relationship with Ferroptosis.
Polyunsaturated fatty acids (PUFAs) undergo lipid peroxidation and conversion into malondialdehyde (MDA). MDA reacts with acetaldehyde to form malondialdehyde-modified low-density lipoprotein (MDA-LDL). We studied unsettled issues in the association between MDA-LDL and the pathophysiology of ASD in 18 individuals with autism spectrum disorders (ASD) and eight age-matched controls. Social behaviors were assessed using the social responsiveness scale (SRS). To overcome the problem of using small samples, adaptive Lasso was used to enhance the interpretability accuracy, and a coefficient of variation was used for variable selections. Plasma levels of the MDA-LDL levels (91.00 ± 16.70 vs. 74.50 ± 18.88) and the DHA/arachidonic acid (ARA) ratio (0.57 ± 0.16 vs. 0.37 ± 0.07) were significantly higher and the superoxide dismutase levels were significantly lower in the ASD group than those in the control group. Total SRS scores in the ASD group were significantly higher than those in the control group. The unbeneficial DHA/ARA ratio induced ferroptosis via lipid peroxidation. Multiple linear regression analysis and adaptive Lasso revealed an association of the DHA/ARA ratio with total SRS scores and increased MDA-LDL levels in plasma, resulting in neuronal deficiencies. This unbeneficial DHA/ARA-ratio-induced ferroptosis contributes to autistic social behaviors and is available for therapy.
Topics: Humans; Docosahexaenoic Acids; Arachidonic Acid; Autism Spectrum Disorder; Lipid Peroxidation; Ferroptosis; Lipoproteins, LDL; Malondialdehyde
PubMed: 37834244
DOI: 10.3390/ijms241914796 -
International Journal of Environmental... Jan 2024Accurate determination of the concentration of alcohols and their metabolites is important in forensics and in several life science areas. A new headspace gas...
Accurate determination of the concentration of alcohols and their metabolites is important in forensics and in several life science areas. A new headspace gas chromatography-mass spectrometry method has been developed to quantify alcohols and their oxidative products using isotope-labeled internal standards. The limit of detection (LOD) of the analytes in the developed method was 0.211 µg/mL for methanol, 0.158 µg/mL for ethanol, 0.157 µg/mL for isopropanol, 0.010 µg/mL for n-propanol, 0.157 µg/mL for acetone, and 0.209 µg/mL for acetaldehyde. The precision and accuracy of the method were evaluated, and the relative standard deviation percentages were found to be less than 3%. This work demonstrates the application of this method, specifically in quantifying the concentration of oxidative products of alcohol and other minor alcohols found in hand sanitizers, which have become an essential household item since the COVID-19 pandemic. Apart from the major components, the minor alcohols found in hand sanitizers include methanol, isopropanol, and n-propanol. The concentration range of these minor alcohols found in ethanol-based hand sanitizer samples was as follows: methanol, 0.000921-0.0151 mg/mL; isopropanol, 0.454-13.8 mg/mL; and n-propanol, 0.00474-0.152 mg/mL. In ethanol-based hand sanitizers, a significant amount of acetaldehyde (0.00623-0.231 mg/mL) was observed as an oxidation product, while in the isopropanol-based hand sanitizer, acetone (0.697 mg/mL) was observed as an oxidation product. The concentration of acetaldehyde in ethanol-based hand sanitizers significantly increased with storage time and temperature, whereas no such increase in acetone concentration was observed in isopropanol-based hand sanitizers with storage time and temperature. In two of the selected hand sanitizers, the acetaldehyde levels increased by almost 200% within a week when stored at room temperature. Additionally, exposing the hand sanitizers to a temperature of 45 °C for 24 h resulted in a 100% increase in acetaldehyde concentration. On the contrary, the acetone level remained constant upon the change in storage time and temperature.
Topics: Humans; Methanol; Acetaldehyde; Hand Sanitizers; Acetone; 2-Propanol; 1-Propanol; Temperature; Gas Chromatography-Mass Spectrometry; Pandemics; Ethanol
PubMed: 38248538
DOI: 10.3390/ijerph21010074 -
BioRxiv : the Preprint Server For... Jan 2024Acetaldehyde is the primary metabolite of alcohol and is present in many environmental sources including tobacco smoke. Acetaldehyde is genotoxic, whereby it can form...
Acetaldehyde is the primary metabolite of alcohol and is present in many environmental sources including tobacco smoke. Acetaldehyde is genotoxic, whereby it can form DNA adducts and lead to mutagenesis. Individuals with defects in acetaldehyde clearance pathways have increased susceptibility to alcohol-associated cancers. Moreover, a mutation signature specific to acetaldehyde exposure is widespread in alcohol and smoking-associated cancers. However, the pathways that repair acetaldehyde-induced DNA damage and thus prevent mutagenesis are vaguely understood. Here, we used to systematically delete genes in each of the major DNA repair pathways to identify those that alter acetaldehyde-induced mutagenesis. We found that deletion of the nucleotide excision repair (NER) genes, or , led to an increase in mutagenesis upon acetaldehyde exposure. Acetaldehyde-induced mutations were dependent on translesion synthesis as well as DNA inter-strand crosslink (ICL) repair in strains. Moreover, whole genome sequencing of the mutated isolates demonstrated an increase in C→A changes coupled with an enrichment of gCn→A changes in the acetaldehyde-treated isolates. The gCn→A mutation signature has been shown to be diagnostic of acetaldehyde exposure in yeast and in human cancers. We also demonstrated that the deletion of the two DNA-protein crosslink (DPC) repair proteases, and , also led to increased acetaldehyde-induced mutagenesis. Defects in base excision repair (BER) led to a mild increase in mutagenesis, while defects in mismatch repair (MMR), homologous recombination repair (HR) and post replicative repair pathways did not impact mutagenesis upon acetaldehyde exposure. Our results in yeast were further corroborated upon analysis of whole exome sequenced liver cancers, wherein, tumors with defects in ERCC1 and ERCC4 (NER), FANCD2 (ICL repair) or SPRTN (DPC repair) carried a higher gCn→A mutation load than tumors with no deleterious mutations in these genes. Our findings demonstrate that multiple DNA repair pathways protect against acetaldehyde-induced mutagenesis.
PubMed: 38260495
DOI: 10.1101/2024.01.07.574575 -
Advanced Science (Weinheim,... Jan 2024Omega-6 fatty acids are the primary polyunsaturated fatty acids in most Western diets, while their role in diabetes remains controversial. Exposure of omega-6 fatty...
Impaired Detoxification of Trans, Trans-2,4-Decadienal, an Oxidation Product from Omega-6 Fatty Acids, Alters Insulin Signaling, Gluconeogenesis and Promotes Microvascular Disease.
Omega-6 fatty acids are the primary polyunsaturated fatty acids in most Western diets, while their role in diabetes remains controversial. Exposure of omega-6 fatty acids to an oxidative environment results in the generation of a highly reactive carbonyl species known as trans, trans-2,4-decadienal (tt-DDE). The timely and efficient detoxification of this metabolite, which has actions comparable to other reactive carbonyl species, such as 4-hydroxynonenal, acrolein, acetaldehyde, and methylglyoxal, is essential for disease prevention. However, the detoxification mechanism for tt-DDE remains elusive. In this study, the enzyme Aldh9a1b is identified as having a key role in the detoxification of tt-DDE. Loss of Aldh9a1b increased tt-DDE levels and resulted in an abnormal retinal vasculature and glucose intolerance in aldh9a1b zebrafish. Transcriptomic and metabolomic analyses revealed that tt-DDE and aldh9a1b deficiency in larval and adult zebrafish induced insulin resistance and impaired glucose homeostasis. Moreover, alterations in hyaloid vasculature is induced by aldh9a1b knockout or by tt-DDE treatment can be rescued by the insulin receptor sensitizers metformin and rosiglitazone. Collectively, these results demonstrated that tt-DDE is the substrate of Aldh9a1b which causes microvascular damage and impaired glucose metabolism through insulin resistance.
Topics: Animals; Insulin; Zebrafish; Insulin Resistance; Gluconeogenesis; Fatty Acids, Omega-6; Aldehydes
PubMed: 38059818
DOI: 10.1002/advs.202302325 -
Journal of Advanced Research Nov 2023Hair loss is a common phenomenon associated with various environmental and genetic factors. Mitochondrial dysfunction-induced oxidative stress has been recognized as a...
INTRODUCTION
Hair loss is a common phenomenon associated with various environmental and genetic factors. Mitochondrial dysfunction-induced oxidative stress has been recognized as a crucial determinant of hair follicle (HF) biology. Aldehyde dehydrogenase 2 (ALDH2) mitigates oxidative stress by detoxifying acetaldehyde. This study investigated the potential role of ALDH2 modulation in HF function and hair growth promotion.
OBJECTIVES
To evaluate the effects of ALDH2 activation on oxidative stress in HFs and hair growth promotion.
METHODS
The modulatory role of ALDH2 on HFs was investigated using an ALDH2 activator. ALDH2 expression in human HFs was evaluated through in vitro immunofluorescence staining. Ex vivo HF organ culture was employed to assess hair shaft elongation, while the fluorescence probe 2',7'- dichlorodihydrofluorescein diacetate was utilized to detect reactive oxygen species (ROS). An in vivo mouse model was used to determine whether ALDH2 activation induces anagen.
RESULTS
During the anagen phase, ALDH2 showed significantly higher intensity than that in the telogen phase, and its expression was primarily localized along the outer layer of HFs. ALDH2 activation promoted anagen phase induction by reducing ROS levels and enhancing reactive aldehyde clearance, which indicated that ALDH2 functions as a ROS scavenger within HFs. Moreover, ALDH2 activation upregulated Akt/GSK 3β/β-catenin signaling in HFs.
CONCLUSIONS
Our findings highlight the hair growth promotion effects of ALDH2 activation in HFs and its potential as a promising therapeutic approach for promoting anagen induction.
PubMed: 37972887
DOI: 10.1016/j.jare.2023.11.014 -
Journal of Dental Sciences Oct 2023Tobacco and alcohol are the well-known carcinogenic agents of oral cavity health. The purpose of this study was to investigate the scientometric characteristics of...
BACKGROUND/PURPOSE
Tobacco and alcohol are the well-known carcinogenic agents of oral cavity health. The purpose of this study was to investigate the scientometric characteristics of alcohol and tobacco use and oral health.
MATERIALS AND METHODS
The papers on alcohol and tobacco use and oral cavity were published since 1885 and 1895, respectively. All the eligible papers were retrieved on March 20, 2023 from the Scopus database.
RESULTS
There are 2529 and 1545 papers on tobacco smoking and alcohol drinking and oral cavity in the Scopus database, respectively. Based on the frequency of keywords in all included papers, both smoking and drinking are involved in mouth neoplasms, oral cancer, leukoplakia, and periodontal diseases. In the papers on tobacco and alcohol use and oral cavity, the same research keywords confirm tobacco and alcohol use associate with oral cancer risk possibly through influencing genetics and gene and protein expression. For the distinctive keywords, nicotine, smoking cessation, and electronic cigarette are unique keywords of tobacco use. Acetaldehyde, alcohol dehydrogenase, and alcohol metabolism are unique ones of alcohol use.
CONCLUSION
This study for the first time reports the scientometric characteristics of tobacco and alcohol use and oral health, which might aid healthcare authorities to promote tobacco and alcohol control measures focused on the necessities of their population.
PubMed: 37799876
DOI: 10.1016/j.jds.2023.05.016