OBJECTIVETo explore the mechanism of male reproductive toxicity induced by acrylonitrile (ACN).

METHODSMale Sprague-Dawley rats were daily administrated ACN by intraperitoneal injection 5 times a week for 13 weeks at the dose of 0, 7.5, 15.0 and 30.0 mg/kg body weight, respectively. The rats were sacrificed and testes were removed at the end of 4, 8, 13 or 15 weeks, respectively. The activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and glutathione S-transferase (GST) and the levels of glutathione (GSH) and malonaldehyde (MDA) were detected in testes.

RESULTSFollowing ACN treatment of 4 weeks, the levels of GSH in ACN 15.0 mg/kg and 30.0 mg/kg group were (7.44 +/- 0.77) mg/g pro and (6.95 +/- 0.77) mg/g pro respectively, and the activity of GSH-Px was (70.89 +/- 4.01) U/mg pro in 30.0 mg/kg group, all of which were significantly higher than the control group (P < 0.05, P < 0.01). After 8 weeks, the levels of GSH decreased to (2.50 +/- 0.94) mg/g pro in ACN 30.0 mg/kg group (P < 0.01); the activities of SOD increased to (102.08 +/- 16.08) NU/mg pro and (113.30 +/- 17.20) NU/mg pro in ACN 15.0 mg/kg and 30.0 mg/kg group (P < 0.01). After 13 weeks, the levels of GSH declined in ACN 15.0 mg/kg and 30.0 mg/kg group, and the activities of GST decreased in ACN 30.0 mg/kg group, and of GSH-Px decreased in both doses group. However, the level of MDA [(0.68 +/- 0.16) nmol/mg pro] were significantly higher in 30.0 mg/kg group than that in control group [(0.38 +/- 0.12) nmol/mg pro] (P < 0.01). 2 weeks after stopping ACN treatment, the level of GSH restored to normal but the levels of MDA or the activity of GSH-Px in 30.0 mg/kg group were still higher or lower respectively than those of control (P < 0.05).

CONCLUSIONACN may impair the balance of antioxidant system, thus induce lipid peroxidation damage to rat testes.

Acrylonitrile ; toxicity ; Animals ; Dose-Response Relationship, Drug ; Glutathione ; metabolism ; Glutathione Peroxidase ; metabolism ; Glutathione Transferase ; metabolism ; Lipid Peroxidation ; drug effects ; Male ; Malondialdehyde ; metabolism ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Testis ; drug effects ; metabolism

OBJECTIVETo evaluate the impacts of three different surgical approaches to urethral stricture on the erectile function of the patients.

METHODSThis study included 126 male patients with urethral stricture, 35 treated by substitution urethroplasty (group A), 52 by anastomotic urethroplasty (group B), and 39 by internal urethroplasty (group C). We evaluated the pre- and postoperative erectile function of the patients using IIEF-5 scores by telephone calls and interviews. We also monitored their nocturnal penile tumescence (NPT).

RESULTSThe IIEF-5 scores in groups A, B and C were 13.5 +/- 4.5, 11.1 +/- 4.8 and 14.5 +/- 4.41 respectively after surgery, all significantly decreased as compared with 17.1 +/- 2.6, 17.1 +/- 3.0 and 17.6 +/- 2.2 preoperatively (P < 0.05).

CONCLUSIONAll the three surgical approaches can reduce IIEF-5 scores in patients with urethral stricture, but anastomotic urethroplasty may induce a higher incidence of erectile dysfunction than the other two approaches.

Adult ; Aged ; Humans ; Intraoperative Period ; Male ; Middle Aged ; Penile Erection ; physiology ; Urethral Stricture ; surgery ; Urologic Surgical Procedures, Male ; methods ; Young Adult

BackgroundLipoxin A4 (LXA4) can alleviate lipopolysaccharide (LPS)-induced acute lung injury (ALI) and acute respiratory distress syndrome through promoting epithelial sodium channel (ENaC) expression in lung epithelial cells. However, how LXA4 promote ENaC expression is still largely elusive. The present study aimed to explore genes and signaling pathway involved in regulating ENaC expression induced by LXA4.

MethodsA549 cells were incubated with LPS and LXA4, or in combination, and analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) of ENaC-α/γ. Candidate genes affected by LXA4 were explored by transcriptome sequencing of A549 cells. The critical candidate gene was validated by qRT-PCR and Western blot analysis of A549 cells treated with LPS and LXA4 at different concentrations and time intervals. LXA4 receptor (ALX) inhibitor BOC-2 was used to test induction of candidate gene by LXA4. Candidate gene siRNA was adopted to analyze its influence on A549 viability and ENaC-α expression. Phosphoinositide 3-kinase (PI3K) inhibitor LY294002 was utilized to probe whether the PI3K signaling pathway was involved in LXA4 induction of candidate gene expression.

ResultsThe A549 cell models of ALI were constructed and subjected to transcriptome sequencing. Among candidate genes, N-myc downstream-regulated gene-1 (NDRG1) was validated by real-time-PCR and Western blot. NDRG1 mRNA was elevated in a dose-dependent manner of LXA4, whereas BOC-2 antagonized NDRG1 expression induced by LXA4. NDRG1 siRNA suppressed viability of LPS-treated A549 cells (treatment vs. control, 0.605 ± 0.063 vs. 0.878 ± 0.083, P = 0.040) and ENaC-α expression (treatment vs. control, 0.458 ± 0.038 vs. 0.711 ± 0.035, P = 0.008). LY294002 inhibited NDRG1 (treatment vs. control, 0.459 ± 0.023 vs. 0.726 ± 0.020, P = 0.001) and ENaC-α (treatment vs. control, 0.236 ± 0.021 vs. 0.814 ± 0.025, P < 0.001) expressions and serum- and glucocorticoid-inducible kinase 1 phosphorylation (treatment vs. control, 0.442 ± 0.024 vs. 1.046 ± 0.082, P = 0.002), indicating the PI3K signaling pathway was involved in regulating NDRG1 expression induced by LXA4.

ConclusionOur research uncovered a critical role of NDRG1 in LXA4 alleviation of LPS-induced A549 cell injury through mediating PI3K signaling to restore ENaC expression.

A549 Cells ; Acute Lung Injury ; metabolism ; Cell Cycle Proteins ; metabolism ; Cell Line ; Epithelial Sodium Channels ; metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; metabolism ; Lipopolysaccharides ; pharmacology ; Lipoxins ; pharmacology ; Signal Transduction ; drug effects

Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.
Aged ; Atrial Fibrillation/complications* ; Cross-Sectional Studies ; Gastrointestinal Microbiome ; Humans ; Lipopolysaccharides ; Male ; Middle Aged ; Prospective Studies