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Archives of Gynecology and Obstetrics Aug 2023Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of systemic vasculitis characterized by autoantibodies against neutrophil... (Review)
Review
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of systemic vasculitis characterized by autoantibodies against neutrophil cytoplasmic antigens (proteinase 3 PR3-ANCA and myeloperoxidase MPO-ANCA) and inflammation of small vessels. AAV include the diagnosis Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), which share many clinical and pathological features. Immunomodulatory therapies have significantly improved prognosis during the last decade. Nevertheless, especially in undiagnosed and thus uncontrolled AAV mortality due to renal impairment or pulmonary haemorrhages is still high. AAV are rare in fertile women, as the typical age of manifestation is above 50 years but there are women with AAV who are or want to become pregnant. This review focusses on how to manage patients with AAV planning to become pregnant and during their pregnancy.
Topics: Humans; Female; Pregnancy; Middle Aged; Male; Granulomatosis with Polyangiitis; Antibodies, Antineutrophil Cytoplasmic; Churg-Strauss Syndrome; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Microscopic Polyangiitis; Myeloblastin; Peroxidase
PubMed: 36104505
DOI: 10.1007/s00404-022-06744-5 -
International Journal of Medical... 2023The prognosis for gastric cancer (GC), a prevalent tumor of the digestive system, is unfavorable. The involvement of glutathione peroxidase 3 (GPX3) in tumorigenesis is...
The prognosis for gastric cancer (GC), a prevalent tumor of the digestive system, is unfavorable. The involvement of glutathione peroxidase 3 (GPX3) in tumorigenesis is significant, yet its specific role in GC remains insufficiently investigated. Thus, the aim of this study was to determine the potential impact of GPX3 on GC and elucidate the underlying mechanism. The expression and survival of GPX3 in GC were analyzed using TCGA data. Additionally, the GPX3 mRNA and protein levels in GC were also assessed using datasets from GTEx, GEPIA, and HPA. A total of 38 pairs of GC tissues, along with their adjacent normal tissues, were collected from the Tianjin Medical University General Hospital, accompanied by detailed clinical information. The expression levels of GPX3 were subsequently determined for the purpose of validation. Following expression, correlation, and survival analyses, we proceeded to investigate the upstream non-coding RNA (ncRNA) of GPX3 using starBase and miRNet. Additionally, the co-expression networks of GPX3 were examined based on LinkedOmics. Lastly, we explored the correlation between GPX3 and immune cell infiltration, as well as the biomarkers of immune cells and immune checkpoints in GC. Furthermore, the GDSC database offered valuable drug sensitivity information. A lower expression of GPX3 was observed in individuals with GC, while a higher expression of GPX3 was associated with a poorer prognosis. The DUBR/hsa-miR-502-3p/GPX3 pathway was identified as the most promising upstream ncRNA pathway related to GPX3 in GC. GO and KEGG enrichment analysis revealed that GPX3 expression was linked to coagulation cascades and cell locomotion. Furthermore, GPX3 levels in GC were positively correlated with immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. The group with low GPX3 expression also exhibited increased sensitivity to 5-fluorouracil, doxorubicin, and other drugs. Collectively, we hypothesized that the potential involvement of non-coding RNAs in the downregulation of GPX3 could contribute to the inhibition of tumor formation during the malignant transition from gastritis to GC. Nevertheless, it was plausible that GPX3 may also facilitate tumor progression to advanced stages by promoting immune cell infiltration and activating immune checkpoints.
Topics: Humans; Prognosis; Stomach Neoplasms; Glutathione Peroxidase; Carcinogenesis; Biomarkers
PubMed: 37790850
DOI: 10.7150/ijms.85253 -
Biomolecules Sep 2023Vascular calcification (VC) is a common complication in patients with chronic kidney disease which increases their mortality. Although oxidative stress is involved in...
Vascular calcification (VC) is a common complication in patients with chronic kidney disease which increases their mortality. Although oxidative stress is involved in the onset and progression of this disorder, the specific role of some of the main redox regulators, such as catalase, the main scavenger of HO, remains unclear. In the present study, epigastric arteries of kidney transplant recipients, a rat model of VC, and an in vitro model of VC exhibiting catalase (Cts) overexpression were analysed. Pericalcified areas of human epigastric arteries had increased levels of catalase and cytoplasmic, rather than nuclear runt-related transcription factor 2 (RUNX2). In the rat model, advanced aortic VC concurred with lower levels of the HO-scavenger glutathione peroxidase 3 compared to controls. In an early model of calcification using vascular smooth muscle cells (VSMCs), Cts VSMCs showed the expected increase in total levels of RUNX2. However, Cts VMSCs also exhibited a lower percentage of the nucleus stained for RUNX2 in response to calcifying media. In this early model of VC, we did not observe a dysregulation of the mitochondrial redox state; instead, an increase in the general redox state was observed in the cytoplasm. These results highlight the complex role of antioxidant enzymes as catalase by regulation of RUNX2 subcellular location delaying the onset of VC.
Topics: Humans; Animals; Rats; Catalase; Core Binding Factor Alpha 1 Subunit; Hydrogen Peroxide; Oxidation-Reduction; Vascular Calcification; Renal Insufficiency, Chronic
PubMed: 37759819
DOI: 10.3390/biom13091419 -
Rheumatology (Oxford, England) Nov 2023
Topics: Humans; Antibodies, Antineutrophil Cytoplasmic; Granulomatosis with Polyangiitis; Peroxidase
PubMed: 37137279
DOI: 10.1093/rheumatology/kead173 -
Scientific Reports Aug 2023Animal and human feces typically include intestinal sulfate-reducing bacteria (SRB). Hydrogen sulfide and acetate are the end products of their dissimilatory sulfate...
Animal and human feces typically include intestinal sulfate-reducing bacteria (SRB). Hydrogen sulfide and acetate are the end products of their dissimilatory sulfate reduction and may create a synergistic effect. Here, we report NADH and NADPH peroxidase activities from intestinal SRB Desulfomicrobium orale and Desulfovibrio piger. We sought to compare enzymatic activities under the influence of various temperature and pH regimes, as well as to carry out kinetic analyses of enzymatic reaction rates, maximum amounts of the reaction product, reaction times, maximum rates of the enzyme reactions, and Michaelis constants in cell-free extracts of intestinal SRB, D. piger Vib-7, and D. orale Rod-9, collected from exponential and stationary growth phases. The optimal temperature (35 °C) and pH (7.0) for both enzyme's activity were determined. The difference in trends of Michaelis constants (K) during exponential and stationary phases are noticeable between D. piger Vib-7 and D. orale Rod-9; D. orale Rod-9 showed much higher K (the exception is NADH peroxidase of D. piger Vib-7: 1.42 ± 0.11 mM) during the both monitored phases. Studies of the NADH and NADPH peroxidases-as putative antioxidant defense systems of intestinal SRB and detailed data on the kinetic properties of this enzyme, as expressed by the decomposition of hydrogen peroxide-could be important for clarifying evolutionary mechanisms of antioxidant defense systems, their etiological role in the process of dissimilatory sulfate reduction, and their possible role in the development of bowel diseases.
Topics: Animals; Humans; Antioxidants; NAD; NADP; Cell Extracts; Desulfovibrio; Peroxidases; Defense Mechanisms; Sulfates
PubMed: 37626119
DOI: 10.1038/s41598-023-41185-3 -
International Journal of Molecular... Jul 2023Oxidases and peroxidases have found application in the field of chlorine-free organic dye degradation in the paper, toothpaste, and detergent industries. Nevertheless,...
Oxidases and peroxidases have found application in the field of chlorine-free organic dye degradation in the paper, toothpaste, and detergent industries. Nevertheless, their widespread use is somehow hindered because of their cost, availability, and batch-to-batch reproducibility. Here, we report the catalytic proficiency of a miniaturized synthetic peroxidase, Fe-Mimochrome VI*a, in the decolorization of four organic dyes, as representatives of either the heterocyclic or triarylmethane class of dyes. Fe-Mimochrome VI*a performed over 130 turnovers in less than five minutes in an aqueous buffer at a neutral pH under mild conditions.
Topics: Peroxidase; Coloring Agents; Reproducibility of Results; Peroxidases; Catalysis
PubMed: 37446248
DOI: 10.3390/ijms241311070 -
Arthritis Research & Therapy Nov 2023Bruton's tyrosine kinase (Btk) is an enzyme expressed in leukocytes other than T lymphocytes and plasma cells and involved in B-cell receptor- and Fcγ receptor...
BACKGROUND
Bruton's tyrosine kinase (Btk) is an enzyme expressed in leukocytes other than T lymphocytes and plasma cells and involved in B-cell receptor- and Fcγ receptor (FcγR)-mediated signal transduction. Btk inhibitors potentially suppress autoantibody production due to the expected inhibitory ability of B lymphocyte differentiation into antibody-producing plasma cells and reduce FcγR-mediated neutrophil activation, including the release of neutrophil extracellular traps (NETs). Microscopic polyangiitis (MPA) is a systemic small-vessel vasculitis characterized by the pathogenic autoantibody, antineutrophil cytoplasmic antibody (ANCA) that reacts with myeloperoxidase (MPO). MPO and MPO-ANCA immune complex (IC)-induced FcγR-mediated NETs are critically involved in MPA pathogenesis. This study aimed to demonstrate the therapeutic efficacy of the Btk inhibitor tirabrutinib on MPA.
METHODS
Various doses of tirabrutinib or vehicle were orally administered to Sprague-Dawley rats daily. Four weeks later, the number of peripheral B lymphocytes was counted, and Btk phosphorylation in B lymphocytes was evaluated by flow cytometry. Human peripheral blood neutrophils were stimulated by MPO and anti-MPO antibody ICs (MPO and anti-MPO-ICs), and Btk and its downstream Vav phosphorylation were assessed by western blotting. The effects of tirabrutinib on MPO and anti-MPO-IC-induced NET formation were examined in vitro. Wistar Kyoto rats were immunized with human MPO to induce experimental MPA and given drug-free or tirabrutinib-containing feed (0.0037% or 0.012%) from day 0 or 28. All rats were euthanized on day 42 for serological and histological evaluation.
RESULTS
Tirabrutinib inhibited Btk phosphorylation without decreasing B lymphocytes in vivo. Neutrophil Btk and Vav were phosphorylated when stimulated with MPO and anti-MPO-ICs. Tirabrutinib suppressed MPO and anti-MPO-IC-induced NET formation in vitro and ameliorated experimental MPA in a dose-dependent manner in vivo. Although MPO-ANCA production was not affected, NET-forming neutrophils in the blood were significantly reduced by tirabrutinib.
CONCLUSIONS
The Btk inhibitor tirabrutinib suppressed MPO and anti-MPO-IC-induced NET formation in vitro and ameliorated experimental MPA by reducing NET-forming neutrophils but not decreasing MPO-ANCA titer in vivo. This study suggests that Btk is a possible therapeutic target in MPA.
Topics: Humans; Rats; Animals; Microscopic Polyangiitis; Antibodies, Antineutrophil Cytoplasmic; Agammaglobulinaemia Tyrosine Kinase; Receptors, IgG; Rats, Sprague-Dawley; Autoantibodies; Rats, Inbred WKY; Peroxidase
PubMed: 37932784
DOI: 10.1186/s13075-023-03201-9 -
Development (Cambridge, England) Oct 2023Lipid droplets (LDs), crucial regulators of lipid metabolism, accumulate during oocyte development. However, their roles in fertility remain largely unknown. During...
Lipid droplets (LDs), crucial regulators of lipid metabolism, accumulate during oocyte development. However, their roles in fertility remain largely unknown. During Drosophila oogenesis, LD accumulation coincides with the actin remodeling necessary for follicle development. Loss of the LD-associated Adipose Triglyceride Lipase (ATGL) disrupts both actin bundle formation and cortical actin integrity, an unusual phenotype also seen when the prostaglandin (PG) synthase Pxt is missing. Dominant genetic interactions and PG treatment of follicles indicate that ATGL acts upstream of Pxt to regulate actin remodeling. Our data suggest that ATGL releases arachidonic acid (AA) from LDs to serve as the substrate for PG synthesis. Lipidomic analysis detects AA-containing triglycerides in ovaries, and these are increased when ATGL is lost. High levels of exogenous AA block follicle development; this is enhanced by impairing LD formation and suppressed by reducing ATGL. Together, these data support the model that AA stored in LD triglycerides is released by ATGL to drive the production of PGs, which promote the actin remodeling necessary for follicle development. We speculate that this pathway is conserved across organisms to regulate oocyte development and promote fertility.
Topics: Animals; Prostaglandins; Lipid Droplets; Actins; Adipogenesis; Drosophila; Lipase; Peroxidases; Drosophila Proteins
PubMed: 37306387
DOI: 10.1242/dev.201516 -
BMC Plant Biology Nov 2023Two spotted spider mite, Tetranychus urticae (Acari: Tetranychidae) is one of the most important plant pests in the world. Due to increased resistance of mites to...
BACKGROUND
Two spotted spider mite, Tetranychus urticae (Acari: Tetranychidae) is one of the most important plant pests in the world. Due to increased resistance of mites to acaricides, it is necessary to use other methods such as inducing resistance in plants by natural compounds for pests' management. Polyamins such as spermine are effective in increasing plant resistance to biotic and abiotic stressors. In this research, the effect of spermine treatments in cucumber plants on life table parameters of T. urticae was investigated. Also, top-down effect of spermine and T. urticae on cucumber biochemical parameters was measured. In the experiments, 1, 2 and 3 mM spermine concentrations were used.
RESULTS
Amongst the spermine treatments, those mites that fed on cucumbers which received 1 mM spermine showed the shortest protonymphal period and higher ovipositon period, fecundity, gross and net reproductive rates and life expectancy compare to control. Treatment with 2 mM spermine lead to the longest teleochrysalis period and shortest range of age-stage-specific fecundity period. In addition, 2 mM spermine lowered intrinsic and finite rate of population increase in T. urticae. The longest larval period of T. urticae was observed in 3 mM spermine. Feeding of T. urticae from cucumber plants increased hydrogen peroxide (HO), malondialdehyde (MDA) content, electrolyte leakage (EL) level and ascorbate peroxidase (APX) activity but inhibited catalase (CAT) activity in this plant. Infested cucumber plants treated with 2 mM spermine showed lower HO and MDA content and highest activity of APX and CAT on day 1 and 3 compare to the others. The 3 mM spermine increased HO content in infested plants during the whole experiment as well as non-infested plants in day 5 and 9 only. This treatment induced the highest MDA content and lowest catalase activity on day1, 3 and 5 of experiment in infested plants.
CONCLUSION
This study showed that 2 mM spermine was the only effective concentration that reduce cucumber sensitivity to T. urticae. The trend of changes in biochemical parameters, especially HO, in 3 mM spermine was abnormal, and this concentration could be considered toxic.
Topics: Animals; Cucumis sativus; Tetranychidae; Spermine; Hydrogen Peroxide; Catalase
PubMed: 37978429
DOI: 10.1186/s12870-023-04573-5 -
Frontiers in Immunology 2023Gliomas have emerged as the predominant brain tumor type in recent decades, yet the exploration of non-apoptotic cell death regulated by the pan-optosome complex, known...
INTRODUCTION
Gliomas have emerged as the predominant brain tumor type in recent decades, yet the exploration of non-apoptotic cell death regulated by the pan-optosome complex, known as pan-apoptosis, remains largely unexplored in this context. This study aims to illuminate the molecular properties of pan-apoptosis-related genes in glioma patients, classifying them and developing a signature using machine learning techniques.
METHODS
The prognostic significance, mutation features, immunological characteristics, and pharmaceutical prediction performance of this signature were comprehensively investigated. Furthermore, GPX8, a gene of interest, was extensively examined for its prognostic value, immunological characteristics, medication prediction performance, and immunotherapy prediction potential.
RESULTS
Experimental techniques such as CCK-8, Transwell, and EdU investigations revealed that GPX8 acts as a tumor accelerator in gliomas. At the single-cell RNA sequencing level, GPX8 appeared to facilitate cell contact between tumor cells and macrophages, potentially enhancing microglial migration.
CONCLUSIONS
The incorporation of pan-apoptosis-related features shows promising potential for clinical applications in predicting tumor progression and advancing immunotherapeutic strategies. However, further in vitro and in vivo investigations are necessary to validate the tumorigenic and immunogenic processes associated with GPX8 in gliomas.
Topics: Humans; Apoptosis; Brain Neoplasms; Glioma; Immunotherapy; Microglia; Peroxidases
PubMed: 37795080
DOI: 10.3389/fimmu.2023.1260169