While the immunomodulation effects of per- and polyfluoroalkyl substances (PFASs) are described on the level of clinical signs in epidemiological studies (e.g., suppressed antibody response after vaccination), the underlying mechanism has still not been fully elucidated. To reveal mechanisms of PFAS exposure on immunity, we investigated the genome-wide transcriptomic changes of peripheral blood mononuclear cells (PBMCs) responding to PFAS exposure (specifically, exposure to PFPA, PFOA, PFNA, PFDA, PFUnDA, PFHxS, and PFOS). Blood samples and the chemical load in the blood were analyzed under the cross-sectional CELSPAC: Young Adults study. The overall aim of the study was to identify sensitive gene sets and cellular pathways conserved for multiple PFAS chemicals. Transcriptome networks related to adaptive immunity were perturbed by multiple PFAS exposure (i.e., blood levels of at least four PFASs). Specifically, processes tightly connected with late B cell development, such as B cell receptor signaling, germinal center reactions, and plasma cell development, were shown to be affected. Our comprehensive transcriptome analysis identified the disruption of B cell development, specifically the impact on the maturation of antibody-secreting cells, as a potential mechanism underlying PFAS immunotoxicity.
- MeSH
- Fluorocarbons * toxicity MeSH
- Alkanesulfonic Acids * MeSH
- Environmental Pollutants * MeSH
- Leukocytes, Mononuclear MeSH
- Humans MeSH
- Young Adult MeSH
- Cross-Sectional Studies MeSH
- Transcriptome MeSH
- Check Tag
- Humans MeSH
- Young Adult MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Despite covering <5% of Earth's terrestrial area, peatlands are crucial for global carbon storage and are hot spots of methane cycling. This study examined the dynamics of aerobic and anaerobic methane oxidation in two undisturbed peatlands: a fen and a spruce swamp forest. Using microcosm incubations, we investigated the effect of ammonium addition, at a level similar to current N pollution processes, on aerobic methane oxidation. Our findings revealed higher methane consumption rates in fen compared to swamp peat, but no effect of ammonium amendment on methane consumption was found. Members of Methylocystis and Methylocella were the predominant methanotrophs in both peatlands. Furthermore, we explored the role of ferric iron and sulfate as electron acceptors for the anaerobic oxidation of methane (AOM). AOM occurred without the addition of an external electron acceptor in the fen, but not in the swamp peat. AOM was stimulated by sulfate and ferric iron addition in the swamp peat and inhibited by ferric iron in the fen. Our findings suggest that aerobic methane oxidizers are not N-limited in these peatlands and that there is an intrinsic potential for AOM in these environments, partially facilitated by ferric iron and sulfate acting as electron acceptors.
Cíl: Porovnat funkční a anatomické výsledky mezi technikou invertovaného laloku a konvenčním odstraněním interní limitující membrány (ILM) při operačním řešení idiopatických makulárních děr (IMD). Metodika: Retrospektivně jsme hodnotili anatomické a funkční výsledky u 67 očí 65 pacientů operovaných pro IMD. Pacienti byli operováni buď technikou konvenčního peelingu ILM (první skupina), nebo technikou invertovaného laloku ILM (druhá skupina). Do první skupiny bylo zařazeno 43 očí 41 pacientů, do druhé skupiny 24 očí 24 pacientů. K operaci jsme indikovali pouze pacienty s IMD stádia 2–4 dle Gasseho klasifikace. Před a dva měsíce po operaci byla vždy stanovená nejlépe korigovaná zraková ostrost (ZO). Dále bylo provedené srovnání obou technik podle průměrného zisku písmen po operaci a efekt operace byl zhodnocen pomocí OCT, zda došlo k uzavření IMD. U obou technik byla provedena 25G PPV s tamponádou SF6. Výsledky: U konvenčního odstranění ILM došlo k uzavření díry u 41 očí. U jednoho oka nedošlo k uzavření díry ani po reoperaci stejnou technikou. Medián zisku písmen ETDRS byl 7,0. ZO zůstala stejná u 2 očí (4,7 %), v 7 případech (16,2 %) se ZO zhoršila a ve všech ostatních případech došlo k jejímu zlepšení (79,0 %). U 16 očí (37,2 %) se ZO zlepšila o 2 a více řádků ETDRS optotypů. U invertovaného flapu došlo k uzavření díry u všech 24 sledovaných očí. Medián zisku písmen ETDRS byl 9,5. ZO zůstala stejná u 2 očí (8,3 %), ve 2 případech (8,3 %) se ZO zhoršila a ve všech ostatních případech došlo k jejímu zlepšení (83,3 %). U 12 očí (50,0 %) se ZO zlepšila o 2 a více řádků ETDRS optotypů. Peroperačně a pooperačně nebyly žádné závažné komplikace. Závěr: Naše studie prokázala bezpečnost a účinnost obou metod. Přestože výsledky nebyly statisticky signifikantní, technika invertovaného laloku měla oproti konvenční technice peelingu ILM v našem souboru očí větší zisk písmen ETDRS (9,5 vs. 7,0) a počet uzavřených děr (100 % vs. 95,3 %).
Aim: To compare functional and anatomical outcomes between the inverted flap technique and conventional removal of the internal limiting membrane (ILM) in the surgical management of idiopathic macular hole (IMH). Material and methods: We retrospectively evaluated the anatomical and functional results in 67 eyes of 65 patients operated on for IMH. The patients were operated on either using the conventional ILM peeling technique (first group) or with the inverted ILM flap technique (second group). 43 eyes of 41 patients were included in the first group, 24 eyes of 24 patients in the second group. We indicated for surgery only patients with IMH stage 2–4 according to the Gasse classification. Best corrected visual acuity (VA) was always determined before and two months after surgery. Furthermore, a comparison of both techniques was made according to the average letter gain after surgery, and the effect of surgery was evaluated using OCT with regard to whether IMH closure succeeded. For both techniques, 25G PPV with SF6 tamponade was performed. Results: Hole closure took place in 41 eyes with conventional ILM removal. In one eye, the hole did not close even after reoperation with the same technique. Median ETDRS letter gain was 7.0. VA remained the same in 2 eyes (4.7%), worsened in 7 cases (16.2%), and improved in all other cases (79.0%). In 16 eyes (37.2%), VA improved by 2 or more lines of ETDRS charts. Using the inverted flap technique, the hole was closed in all 24 monitored eyes. Median ETDRS letter gain was 9.5. VA remained the same in 2 eyes (8.3%), worsened in 2 cases (8.3%), and improved in all other cases (83.3%). In 12 eyes (50.0%), VA improved by 2 or more lines of ETDRS charts. There were no serious complications intraoperatively or postoperatively. Conclusion: Our study demonstrated the safety and efficacy of both methods. Although the results were not statistically significant, the inverted flap technique recorded a greater ETDRS letter gain (9.5 vs. 7.0) and proportion of closed holes (100% vs. 95.3%) compared to the conventional ILM peeling technique in our set of eyes.
- Keywords
- invertovaný lalok, peeling MLI,
- MeSH
- Humans MeSH
- Ophthalmologic Surgical Procedures * classification methods statistics & numerical data MeSH
- Retinal Perforations * surgery classification therapy MeSH
- Retrospective Studies MeSH
- Trypan Blue therapeutic use MeSH
- Vitrectomy classification methods MeSH
- Endotamponade classification methods MeSH
- Treatment Outcome MeSH
- Visual Acuity MeSH
- Check Tag
- Humans MeSH
Optimal conditioning prior to allogeneic hematopoietic stem cell transplantation for children with non-malignant diseases is subject of ongoing research. This prospective, randomized, phase 2 trial compared safety and efficacy of busulfan with treosulfan based preparative regimens. Children with non-malignant diseases received fludarabine and either intravenous (IV) busulfan (4.8 to 3.2 mg/kg/day) or IV treosulfan (10, 12, or 14 g/m2/day). Thiotepa administration (2 × 5 mg/kg) was at the investigator's discretion. Primary endpoint was freedom from transplantation (treatment)-related mortality (freedom from TRM), defined as death between Days -7 and +100. Overall, 101 patients (busulfan 50, treosulfan 51) with at least 12 months follow-up were analyzed. Freedom from TRM was 90.0% (95% CI: 78.2%, 96.7%) after busulfan and 100.0% (95% CI: 93.0%, 100.0%) after treosulfan. Secondary outcomes (transplantation-related mortality [12.0% versus 3.9%]) and overall survival (88.0% versus 96.1%) favored treosulfan. Graft failure was more common after treosulfan (n = 11), than after busulfan (n = 2) while all patients were rescued by second procedures except one busulfan patient. CTCAE Grade III adverse events were similar in both groups. This study confirmed treosulfan to be an excellent alternative to busulfan and can be safely used for conditioning treatment in children with non-malignant disease.
- MeSH
- Busulfan therapeutic use MeSH
- Child MeSH
- Humans MeSH
- Graft vs Host Disease * etiology MeSH
- Transplantation Conditioning methods MeSH
- Prospective Studies MeSH
- Hematopoietic Stem Cell Transplantation * methods MeSH
- Vidarabine therapeutic use MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase II MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
Myricetin (MYR) and ampelopsin (AMP, or dihydromyricetin) are flavonoid aglycones found in certain plants and dietary supplements. During the presystemic biotransformation of flavonoids, mainly sulfate and glucuronide derivatives are produced, which are the dominant metabolites in the circulation. In this study, we tested the interactions of MYR, myricetin-3'-O-sulfate (M3'S), AMP, and ampelopsin-4'-O-sulfate (A4'S) with human serum albumin (HSA), cytochrome P450 enzymes (CYPs), and organic anion-transporting polypeptides (OATPs) using in vitro models, including the recently developed method for measuring flavonoid levels in living cells. M3'S and MYR bound to albumin with high affinity, and they showed moderate displacing effects versus the Site I marker warfarin. MYR, M3'S, AMP, and A4'S exerted no or only minor inhibitory effects on CYP2C9, CYP2C19, and CYP3A4 enzymes. M3'S and MYR caused considerable inhibitory actions on OATP1B1 at low micromolar concentrations (IC50 = 1.7 and 6.4 μM, respectively), while even their nanomolar levels resulted in strong inhibitory effects on OATP2B1 (IC50 = 0.3 and 0.4 μM, respectively). In addition, M3'S proved to be a substrate of OATP1B1 and OATP2B1. These results suggest that MYR-containing dietary supplements may affect the OATP-mediated transport of certain drugs, and OATPs are involved in the tissue uptake of M3'S.
- MeSH
- Cytochrome P-450 CYP3A metabolism MeSH
- Cytochrome P-450 CYP2C9 metabolism MeSH
- Flavonoids * pharmacology MeSH
- Flavonols pharmacology MeSH
- Humans MeSH
- Liver-Specific Organic Anion Transporter 1 * metabolism MeSH
- Organic Anion Transporters * metabolism MeSH
- Serum Albumin metabolism MeSH
- Sulfates metabolism MeSH
- Cytochrome P-450 Enzyme System metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Laccase-producing fungus (MY3) was successfully isolated from soil samples collected from Mansoura Governorate, Egypt. This fungal isolate has shown a high laccase production level over other isolated fungi. The identity of this isolate was determined by the molecular technique 18SrRNA as Curvularia lunata MY3. The enzyme purification was performed using ammonium sulfate precipitation followed by Sephacryl S-200 and DEAE-Sepharose column chromatography. The denatured enzyme using SDS-PAGE had a molar mass of 65 kDa. The purified laccase had an optimum temperature at 40 °C for enzyme activity with 57.3 kJ/mol activation energy for 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) oxidation. The enzyme had an optimum pH of 5.0, and it has shown a high stability at the acidic range (4.5 to 5.5). Mn2+ and Mg2+ ions enhanced the enzyme activity, while most of the enzyme activity was inhibited by Hg2+. Some compounds such as 2-mercaptoethanol, L-cysteine, and sodium azide at a concentration of 10 mmol/L had shown a high suppression effect on the enzyme activity. The enzyme strongly oxidized ABTS and syringaldazine and moderately oxidized DMP and guaiacol. The antimicrobial activity of the purified enzyme towards three pathogenic strains (Escherichia coli ATCC-25922, Staphylococcus aureus NRRLB-767, and Candida albicans ATCC-10231) was evaluated for the potential use as an antimicrobial therapeutic enzyme.
Sulfur-oxidizing bacteria (SOB) are versatile microorganisms known for their ability to oxidize various reduced sulfur compounds, namely, elemental sulfur (S0), hydrogen sulfide (H2S), tetrathionate (S4O62-), and trithionate (S3O62-) to sulfate (SO42-). In this study, out of twelve SOB isolates from rice rhizosphere, five were screened based on their sulfur oxidation potential, viz., SOB1, SOB2, SOB3, SOB4, and SOB5, and were identified as Ochrobactrum soli SOB1, Achromobacter xylosoxidans SOB2, Stenotrophomonas maltophilia SOB3, Brucella tritici SOB4, and Stenotrophomonas pavanii SOB5, respectively. All the isolates displayed chemolithotrophic nutritional mode by consuming thiosulfate and accumulating trithionate and tetrathionate in the growth medium which is ultimately oxidized to sulfate. The strains were authenticated with the production of thiosulfate oxidizing enzymes such as rhodanese and sulfite oxidase. Despite their tendency to oxidize reduced sulfur compounds, B. tritici SOB4 and S. pavanii SOB5 were also found to possess phosphate and zinc solubilization potential, acetic acid, and indole acetic acid (IAA) production and 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity. The presence of sulfanyl (R-SH) groups was noticed in the A. xylosoxidans SOB2. Elemental sulfur conversion into sulfate was noted in the S. maltophilia SOB3, and hydrogen sulfide conversion into sulfate was observed in the Ochromobacter soli SOB1. Sulfur oxidation potential coupled with beneficial properties of the isolates widen the knowledge on SOB.
BACKGROUND: Endothelial glycocalyx (EG) plays a crucial role in maintaining the plasma proteins within the intravascular space. OBJECTIVE: We studied whether exogenous albumin protects the EG in an experimental model of EG enzymatic damage in rats. METHODS: Rats were divided into three groups of 10 animals that received (1) Evans blue (2) Evans blue + hyaluronidase, or (3) Evans blue + hyaluronidase + 20% human albumin via the tail vein. Spectrophotometric analysis was performed 2 h later to quantify the leakage of Evans blue-labeled albumin into the heart, lungs, brain, kidneys, liver, small intestine, spleen, and skeletal muscle. RESULTS: Administration of hyaluronidase numerically increased the capillary leakage of Evans blue in all examined tissues. Co-administration of albumin decreased the leakage of albumin in all tissues except the heart. In the lungs, the ratio between the absorbance and dry organ weight decreased from 5.3 ± 2.4 to 1.7 ± 0.5 (mean ± SD) (P < 0.002), and in the liver, the absorbance decreased from 2.2 ± 0.7 to 1.5 ± 0.4 (P < 0.011). CONCLUSION: Exogenous albumin decreased the capillary leakage of albumin which was interpreted as a sign of maintained EG integrity.
- MeSH
- Albumins * metabolism MeSH
- Endothelium, Vascular drug effects metabolism MeSH
- Evans Blue MeSH
- Glycocalyx * metabolism drug effects MeSH
- Hyaluronoglucosaminidase pharmacology MeSH
- Capillary Permeability * drug effects MeSH
- Rats MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Rats, Wistar MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Effective treatment of patients with autism spectrum disorder (ASD) is still absent so far. Taurine exhibits therapeutic effects towards the autism-like behaviour in ASD model animals. Here, we determined the mechanism of taurine effect on hippocampal neurogenesis in genetically inbred BTBR T+ tf/J (BTBR) mice, a proposed model of ASD. In this ASD mouse model, we explored the effect of oral taurine supplementation on ASD-like behaviours in an open field test, elevated plus maze, marble burying test, self-grooming test, and three-chamber test. The mice were divided into four groups of normal controls (WT) and models (BTBR), who did or did not receive 6-week taurine supplementation in water (WT, WT+ Taurine, BTBR, and BTBR+Taurine). Neurogenesis-related effects were determined by Ki67 immunofluorescence staining. Western blot analysis was performed to detect the expression of phosphatase and tensin homologue deleted from chromosome 10 (PTEN)/mTOR/AKT pathway-associated proteins. Our results showed that taurine improved the autism-like behaviour, increased the proliferation of hippocampal cells, promoted PTEN expression, and reduced phosphorylation of mTOR and AKT in hippocampal tissue of the BTBR mice. In conclusion, taurine reduced the autism-like behaviour in partially inherited autism model mice, which may be associa-ted with improving the defective neural precursor cell proliferation and enhancing the PTEN-associated pathway in hippocampal tissue.
- MeSH
- Autistic Disorder * metabolism drug therapy MeSH
- Behavior, Animal drug effects MeSH
- PTEN Phosphohydrolase * metabolism MeSH
- Hippocampus * metabolism drug effects MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Neurogenesis * drug effects MeSH
- Autism Spectrum Disorder metabolism drug therapy MeSH
- Cell Proliferation drug effects MeSH
- Proto-Oncogene Proteins c-akt * metabolism MeSH
- Signal Transduction * drug effects MeSH
- Taurine * pharmacology MeSH
- TOR Serine-Threonine Kinases * metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
