Overexpression of CFH gene in pterygiumv patients

Purpose: To investigate the expression of complement factors in pterygium tissues compared to normal conjunctival samples, using next-generation RNA sequencingMethods: Twenty pterygium and 20 healthy conjunctival samples were obtained from 19 patients who consented to pterygium excision and conjunctival autograft surgery. Tissues (pterygium and normal conjunctiva) were analyzed using next-generation RNA sequencing. Significant gene lists were obtained using DAVID, GSEA, and KEGG for enriched pathway analyses of differentially expressed genes. Realtime polymerase chain reaction was performed to validate differential expressions of complement factors.Results: There was 3.15 ± 2.6, 3.21 ± 4.6, 3.03 ± 1.83, 4.28 ± 6.12, and 4.96 ± 1.89-fold increase in the expression of CFH, C2, C1QB, C1QC, and MASP1, respectively, in pterygium samples compared to normal conjunctival samples. Pterygium size correlated well with the expression of CFH, C1QB, C1QC and MASP1.Conclusion: Alternative and lectin complement systems are activated in pterygia samples compared to normal conjunctival samples.Keywords: Pterygium; Complement factor; RNA sequencin

The Effect of Environmental Enrichment on Glutathione-Mediated Xenobiotic Metabolism and Antioxidation in Normal Adult Mice

Olfactory bulb (OB) plays an important role in protecting against harmful substances via the secretion of antioxidant and detoxifying enzymes. Environmental enrichment (EE) is a common rehabilitation method and known to have beneficial effects in the central nervous system. However, the effects of EE in the OB still remain unclear. At 6 weeks of age, CD-1® (ICR) mice were assigned to standard cages or EE cages. After 2 months, we performed proteomic analysis. Forty-four up-regulated proteins were identified in EE mice compared to the control mice. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes Pathway demonstrated that the upregulated proteins were mainly involved in metabolic pathways against xenobiotics. Among those upregulated proteins, 9 proteins, which participate in phase I or II of the xenobiotic metabolizing process and are known to be responsible for ROS detoxification, were validated by qRT-PCR. To explore the effect of ROS detoxification mediated by EE, glutathione activity was measured by an ELISA assay. The ratio of reduced glutathione to oxidized glutathione was significantly increased in EE mice. Based on a linear regression analysis, GSTM2 and UGT2A1 were found to be the most influential genes in ROS detoxification. For further analysis of neuroprotection, the level of iNOS and the ratio of Bax to Bcl-2 were significantly decreased in EE mice. While TUNEL+ cells were significantly decreased, Ki67+ cells were significantly increased in EE mice, implicating that EE creates an optimal state for xenobiotic metabolism and antioxidant activity. Taken together, our results suggested that EE protects olfactory layers via the upregulation of glutathione-related antioxidant and xenobiotic metabolizing enzymes, eventually lowering ROS-mediated inflammation and apoptosis and increasing neurogenesis. This study may provide an opportunity for a better understanding of the beneficial effects of EE in the OB

Factors associated with stroke in patients with paroxysmal atrial fibrillation beyond CHADS2 score

Background: This study was conducted to investigate factors associated with stroke in pa­tients with paroxysmal atrial fibrillation (PAF) beyond CHADS2 score in terms of left ventricular (LV) diastolic function or left atrial (LA) function. Methods: One hundred and sixty-one patients with PAF and age less than 75 (mean age 61 ± 10; 69 male) who underwent transthoracic echocardiography were investigated. Patients were divided into two groups according to the stroke status (group 1 — no stroke vs. group 2 — presence of stroke). Baseline echocardiographic parameters and LA segmental (4 segments: basal septal, lateral, inferior, and anterior) strain rate (SR) during normal sinus rhythm were analyzed. Results: CHAD score (except S2) was similar between the two groups (0.6 ± 0.7 vs. 0.9 ± 0.7, p = 0.125). Patients with stroke had slightly lower body mass index (24.5 ± 2.7 vs. 23.4 ± ± 2.4, p = 0.052). Echocardiographic parameters did not show any differences in both systolic and diastolic functions between the two groups, however elevated E/E’ ratio was noted (9.5 ± ± 3.8 vs. 11.6 ± 3.9, p = 0.010) due to higher E velocity (63.5 ± 15.9 vs. 70.9 ± 16.0 cm/s, p = 0.046). In the analysis of LA SR, there are no differences of SR among the 4 segments. However, standard deviations (SD) of time to peak SR (SD of tA-SR) of the 4 segments were higher in patients with stroke (10.9 ± 9.9 vs. 22.1 ± 18.1 ms, p = 0.009) which indicates dyssynchronous contraction of LA. In multivariate analysis, SD of tA-SR (OR 1.074, CI 1.024–1.128, p = 0.004) and elevated E/E’ (OR 1.189, CI 1.006–1.406, p = 0.048) were independently associated with stroke in patients with PAF. Conclusions: Elevated E velocity, E/E’ and SD of tA-SR were associated with occurrence of stroke in patients with PAF even with similar CHAD scores. Increased SD of tA-SR and E/E’ were independently associated with stroke in patients with PAF.

Experimental Study on the Acellular Demal Matrix Graft for the Root Coverage in Dog

Mucogingival surgery is a plastic surgical procedure designed to correct defects in the morphology, position, and dimensions of the gingiva surrounding the teeth. Many surgical techniques have been reported in mucogingival surgery. Since these procedures also include the soft tissue esthetic approach, the term periodontal plastic surgery has been proposed to be more appropriate.1 Root coverage is a procedure that falls with this definition, and it has attracted more interest than others

Epstein-Barr Virus and p16INK4A Methylation in Squamous Cell Carcinoma and Precancerous Lesions of the Cervix Uteri

Methylation of p16 is an important mechanism in cervical carcinogenesis. However, the relationship between cervical squamous cell carcinoma (SCC) and Epstein-Barr virus (EBV) remains controversial. Here, we explored whether EBV infection and/or p16 gene inactivation would play any role in cervical carcinogenesis. Eighty-two specimens included 41 invasive SCCs, 30 cervical intraepithelial neoplasm (CIN; CIN 1, 11 cases, CIN II, 3 cases, CIN III 16 cases) and 11 nonneoplastic cervices. EBV was detected by polymerase chain reaction (PCR) for EBNA-1 and in situ hybridization for EBER-1. The p16 methylation-status and the expression of p16 protein were studied by methylation-specific PCR and immunohistochemistry, respectively. The materials were divided into four groups: 1) nonneoplastic cervices, 2) CIN I, 3) CIN II-III and 4) invasive SCCs. p16 methylation and p16 immunoexpressions increased in CIN and invasive SCCs than nonneoplastic tissue. p16-methylation and p16-immunoreactivities were higher in the EBV-positive group (p=0.009, p<0.001) than in the EBV-negative group. EBV was detected more frequently in CIN and SCCs than nonneoplastic cervices. In conclusion, a correlation between p16 methylation, p16 immunoreactivity and the detection of EBV strongly suggested that the cooperation of EBV and p16 gene may play a synergic effect on cell cycle deregulation

The Effectiveness of Budesonide Nasal Irrigation After Endoscopic Sinus Surgery in Chronic Rhinosinusitis With Asthma

Objectives Budesonide nasal irrigation was introduced recently for postoperative management of patients with chronic rhinosinusitis. The safety and therapeutic effectiveness of this procedure is becoming accepted by many physicians. The objective of this study was to evaluate the efficacy of postoperative steroid irrigation in patients with chronic rhinosinusitis and asthma. Methods This prospective study involved 12 chronic rhinosinusitis patients with nasal polyps and asthma who received oral steroid treatment for recurring or worsening disease. The 22-item Sinonasal Outcomes Test (SNOT-22) and Lund-Kennedy endoscopy scores were checked before nasal budesonide irrigation, and 1, 2, 4, and 6 months after irrigation. We also calculated the total amount of oral steroids and inhaled steroids in the 6 months before irrigation and the 6 months after it. Results The mean SNOT-22 score improved from 30.8±14.4 before irrigation to 14.2±8.7 after 6 months of irrigation (P=0.030). The endoscopy score also improved from 7.4±4.7 before irrigation to 2.2±2.7 after 6 months (P<0.001). The total amount of oral steroid was decreased from 397.8±97.6 mg over the 6 months before irrigation to 72.7±99.7 mg over the 6 months after irrigation (P<0.001). Conclusion Nasal irrigation with budesonide is an effective postoperative treatment for chronic rhinosinusitis with asthma, which recurs frequently, reducing the oral steroid intake

Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19

IntroductionTocilizumab, a humanized anti-interleukin-6 receptor (IL-6R) antibody, is recommended for the treatment of severe to critical coronavirus diseases 2019 (COVID-19). However, there were conflicting results on the efficacy of tocilizumab. Therefore, we hypothesized that the differences in tocilizumab efficacy may stem from the different immune responses of critical COVID-19 patients. In this study, we described two groups of immunologically distinct COVID-19 patients, based on their IL-6 response.MethodsWe prospectively enrolled critical COVID-19 patients, requiring oxygen support with a high flow nasal cannula or a mechanical ventilator, and analyzed their serial samples. An enzyme-linked immunosorbent assay and flow cytometry were used to evaluate the cytokine kinetics and cellular immune responses, respectively.ResultsA total of nine patients with critical COVID-19 were included. The high (n = 5) and low IL-6 (n = 4) groups were distinguished by their peak serum IL-6 levels, using 400 pg/mL as the cut-off value. Although the difference of flow cytometric data did not reach the level of statistical significance, the levels of pro-inflammatory cytokines and the frequencies of intermediate monocytes (CD14+CD16+), IFN-γ+ CD4+ or CD8+ T cells, and HLA-DR+PD-1+ CD4+ T cells were higher in the high IL-6 group than in the low IL-6 group.ConclusionThere were distinctive two groups of critical COVID-19 according to serum IL-6 levels having different degrees of cytokinemia and T-cell responses. Our results indicate that the use of immune modulators should be more tailored in patients with critical COVID-19

Differentially Expressed Potassium Channels Are Associated with Function of Human Effector Memory CD8+T cells

The voltage-gated potassium channel, Kv1.3, and the Ca2+-activated potassium channel, KCa3.1, regulate membrane potentials in T cells, thereby controlling T cell activation and cytokine production. However, little is known about the expression and function of potassium channels in human effector memory ( EM) CD8+ T cells that can be further divided into functionally distinct subsets based on the expression of the interleukin ( IL)-7 receptor alpha ( IL-7R alpha) chain. Herein, we investigated the functional expression and roles of Kv1.3 and KCa3.1 in EM CD8+ T cells that express high or low levels of the IL-7 receptor alpha chain ( IL-7R alpha(high) and IL-7R alpha(low), respectively). In contrast to the significant activity of Kv1.3 and KCa3.1 in IL-7Rahigh EM CD8+ T cells, IL-7Ralow EM CD8+ T cells showed lower expression of Kv1.3 and insignificant expression of KCa3.1. Kv1.3 was involved in the modulation of cell proliferation and IL-2 production, whereas KCa3.1 affected the motility of EM CD8+ T cells. The lower motility of IL-7Ralow EM CD8+ T cells was demonstrated using transendothelial migration and motility assays with intercellular adhesion molecule 1-and/or chemokine stromal cell-derived factor-1 alpha-coated surfaces. Consistent with the lower migration property, IL-7Ralow EM CD8+ T cells were found less frequently in human skin. Stimulating IL-7Ralow EM CD8+ T cells with IL-2 or IL-15 increased their motility and recovery of KCa3.1 activity. Our findings demonstrate that Kv1.3 and KCa3.1 are differentially involved in the functions of EM CD8+ T cells. The weak expression of potassium channels in IL-7Ralow EM CD8+ T cells can be revived by stimulation with IL-2 or IL-15, which restores the associated functions. This study suggests that IL-7Rahigh EM CD8+ T cells with functional potassium channels may serve as a reservoir for effector CD8+ T cells during peripheral inflammation.112Ysciescopu

Boosting the bifunctionality and durability of cobalt-fluoride-oxide nanosheets for alkaline water splitting through nitrogen-plasma-promoted electronic regulation and structural reconstruction

Designing cost-effective and durable bifunctional electrocatalysts with high activity for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is crucial for large-scale hydrogen production through water splitting. However, many electrocatalysts undergo surface or bulk reconstruction, leading to an unstable catalytic activity. In this study, we present a facile N2 plasma strategy to enhance the electrocatalytic activity of cobalt-fluoride-oxide (CoFO, herein NCoFO) nanosheets while maintaining reasonably stable performance. The optimized NCoFO nanosheets grown on carbon cloth through a 60 s N2 plasma treatment (NCoFO/CC-60) exhibit remarkable performance with low overpotentials of 203 mV and 230 mV at 10 mA cm-2 for the HER and the OER, respectively. Density functional theory calculations revealed that the enhanced catalytic performance is attributed to the regulated local electronic configuration resulting from plasma treatment. Furthermore, the assembled alkaline electrolyzer NCoFO/CC-60||NCoFO/CC-60 requires an extremely low voltage of 1.48 V to attain 10 mA cm-2 for over a 150 h operation, which is superior to the values obtained for Pt/C||RuO2 (1.50 V) and CoFO/CC||CoFO/CC (1.55 V)