Optical coherence tomography parameters as prognostic factors for stereopsis after vitrectomy for unilateral epiretinal membrane: a cohort study.

This retrospective cohort study explored the relationship between monocular and interocular optical coherence tomography (OCT) parameters and stereopsis in 56 patients undergoing pars plana vitrectomy (PPV) for unilateral idiopathic epiretinal membrane (IERM). IERM impairs visual functions, with symptoms ranging from asymptomatic to severe impairment. Despite established surgical interventions, including PPV with membrane peeling, the impact on advanced three-dimensional visual functions such as stereopsis remains inadequately investigated. All subjects were assessed for stereopsis, visual acuity, and metamorphopsia, alongside spectral domain OCT parameters. These visual functions significantly improved 3-month postoperatively. Central retinal thickness at the fovea, parafovea, and perifovea (CFT, CRT-3 mm, and CRT-6 mm), ectopic inner foveal layer thickness, and retinal layer thickness notably decreased 1 week to 3 months after surgery. The interocular difference in OCT parameters between bilateral eyes was included as a parameter. Baseline CRT-3 mm difference and inner nuclear layer (INL) thickness were independently correlated with postoperative stereopsis on the Titmus Stereo Test, while baseline CRT-6 mm difference and INL thickness were independently related to stereopsis on the TNO stereotest. This study highlights the substantial enhancement in stereopsis post-IERM surgery, with both interocular and monocular OCT parameters independently influencing postoperative stereopsis. These findings underscore the importance of retinal microstructures in assessing and predicting stereopsis in IERM patients after vitrectomy.

Down-regulation of miR-155 inhibits inflammatory response in human pulmonary microvascular endothelial cells infected with influenza A virus by targeting sphingosine-1-phosphate receptor 1.

BACKGROUND: Endothelial cells play a key role in the cytokine storm caused by influenza A virus. MicroRNA-155 (miR-155) is an important regulator in inflammation. Its role in the inflammatory response to influenza A infection, however, has yet to be elucidated. In this study, we explored the role as well as the underlying mechanism of miR-155 in the cytokine production in influenza A-infected endothelial cells. METHODS: Human pulmonary microvascular endothelial cells (HPMECs) were infected with the influenza A virus strain H1N1. The efficiency of H1N1 infection was confirmed by immunofluorescence. The expression levels of proinflammatory cytokines and miR-155 were determined using real-time polymerase chain reaction. A dual-luciferase reporter assay characterized the interaction between miR-155 and sphingosine-1-phosphate receptor 1 (S1PR1). Changes in the target protein levels were determined using Western blot analysis. RESULTS: MiR-155 was elevated in response to the H1N1 infection in HPMECs (24 h post-infection vs. 0 h post-infection, 3.875 ±â€Š0.062 vs. 1.043 ±â€Š0.013, P = 0.001). Over-expression of miR-155 enhanced inflammatory cytokine production (miR-155 mimic vs. negative control, all P < 0.05 in regard of cytokine levels) and activation of nuclear factor kappa B in infected HPMECs (miR-155 mimic vs. negative control, P = 0.004), and down-regulation of miR-155 had the opposite effect. In addition, S1PR1 was a direct target of miR-155 in the HPMECs. Inhibition of miR-155 enhanced the expression of the S1PR1 protein. Down-regulation of S1PR1 decreased the inhibitory effect of the miR-155 blockade on H1N1-induced cytokine production and nuclear factor kappa B activation in HPMECs. CONCLUSION: MiR-155 maybe modulate influenza A-induced inflammatory response by targeting S1PR1.

Inhibition of autophagy and chemokine induction by sphingosine 1-phosphate receptor 1 through NF-κB signaling in human pulmonary endothelial cells infected with influenza A viruses.

Endothelial cells have been considered the central regulators of cytokine storm in the respiratory system during influenza virus infection. Studies have found that elevated autophagy could be an essential component of viral pathogenesis in influenza infection. However, few studies have been performed to examine whether autophagy occurs in human pulmonary endothelial cells (HPMECs). In addition, specific mechanisms about how inflammatory responses are regulated in the endothelial cells remain unclear. We hypothesized that infection of influenza A viruses subtypes H1N1 and H9N2 triggered autophagy, which played an important role in the induction of proinflammatory cytokines, both in human lung epithelial A549 cells and in HPMECs. In this report, we showed our evidence that blockage of autophagy significantly inhibited influenza virus-induced proinflammatory responses and suppressed viral replication. Our data indicated that the inhibition of the cytokine response and viral replication was affected by increasing the expression of endothelial sphingosine 1-phosphate receptor 1 (S1PR1), which might be through the regulation of NF-κB signaling. Overexpression of S1PR1 decreased p65 phosphorylation and translocation into the nucleus. Furthermore, we demonstrated that S1PR1 stimulation inhibited Akt-mTOR signaling, which might contribute to activation of autophagy in HPMECs. Thus, our study provides knowledge crucial to better understanding novel mechanisms underlying the S1PR1-mediated attenuation of cytokine amplification in the pulmonary system during influenza virus infection.

Pyrroline-5-carboxylate reductase 1 promotes proliferation and inhibits apoptosis in non-small cell lung cancer.

Disordered tumor cell metabolism is involved in the process of tumorigenesis. Proline metabolism is of critical importance for tumor cells, and pyrroline-5-carboxylate reductase 1 (PYCR1), a key proline biosynthesis enzyme, has been reported to be overexpressed in prostate cancer and to promote tumor cell growth in breast cancer. The present study investigated the relationship between PYCR1 and non-small cell lung cancer (NSCLC). The results revealed that PYCR1 was overexpressed in NSCLC tumor tissues compared with adjacent normal tissues. High PYCR1 expression was associated with poor prognosis in patients with NSCLC. Following knockdown of PYCR1 by small interfering RNA, cell proliferation was revealed to be significantly inhibited and the cell cycle was arrested, while apoptosis was increased in SPC-A1 and H1703 NSCLC cells. Furthermore, the silencing of PYCR1 resulted in the downregulation of expression of the cell cycle regulator cyclin D1, the regulator of the mitochondrial apoptotic pathway B-cell lymphoma-2, and B-cell lymphoma-extra large. The results of the present study indicated the involvement of PYCR1 in the proliferation and apoptosis of NSCLC. Therefore, PYCR1 may be a novel therapeutic target for inhibiting cell proliferation in lung cancer.

Influenza virus non­structural protein 1 inhibits the production of interferon ß of alveolar epithelial cells upon the infection of influenza A H1N1.

Influenza A affects a large population worldwide. Influenza virus evades immune responses via various mechanisms, including through the modification of the immune microenvironment. Influenza virus non­structural protein 1 (NS1) encoded by the virus genome inhibits type I interferon (IFN) signaling pathways, which is essential for viral clearance. However, the precise mechanisms of NS1­mediated immune suppression remain poorly understood. The results of the present study demonstrated that mice infected with NS1­expressing influenza A H1N1 virus had lower expression levels of IFNß in the lung. In addition, it was revealed that the human alveolar epithelial A549 cell line infected with influenza virus A H1N1 produced antiviral IFNß. The production of IFNß during infection was demonstrated to be a self­dependent autocrine process. A549 cells transfected with H1N1 NS1 lost the ability to produce IFNß upon H1N1 infection or IFNß stimulation. NS1 inhibited the expression of IFN receptors. Furthermore, NS1 inhibited the activation of signal transducers and activators of transcription (STAT)1 and STAT2, as well as the consequent IFNß production. These data indicate that NS1 serves an important role during virus evasion by affecting the production of IFNß via multiple mechanisms.

Sphingosine 1-phosphate receptor 1 (S1PR1) agonist CYM5442 inhibits expression of intracellular adhesion molecule 1 (ICAM1) in endothelial cells infected with influenza A viruses.

BACKGROUND: Influenza A virus infection and its complications effect a large population worldwide. Endothelial cells are an important component in lung inflammation caused by influenza A virus infection. The roles of endothelial sphingosine 1-phophate receptor 1 (S1PR1) in the regulation of molecules involved in leukocyte recruitment during influenza A virus infection still remain unknown. In this report, we tested our hypothesis that S1PR1 agonist CYM5442 inhibits expression of intracellular adhesion molecules 1 (ICAM1) in endothelial cells infected with influenza A virus. METHODS: Human pulmonary microvascular endothelial cells (HPMEC) were infected with influenza A virus H1N1. Expression of cytokines, chemokines, interferons, and cellular adhesion molecules was measured by q-PCR. Expression of ICAM1 was further tested by Western Blotting. A S1PR1 agonist CYM5442 was added to the culture media to assess CYM5442's inhibitory effects during virus infection. RESULTS: HPMEC could be infected with H1N1 and responded to produce pro-inflammatory cytokines, chemokines, type I interferons, and cellular adhesion molecules. Addition of CYM5442 in culture media reduced the production of ICAM1 via a dosage- and time-dependent manner. CYM5442 inhibited the activation of nuclear factor (NF)-κB. The regulatory effects of CYM5442 were ß-arrestin2-dependent. CONCLUSION: Activated S1PR1 signaling regulates the production of cellular adhesion molecules by inhibiting NF- κB activation via a ß-arrestin2-dependent manner.

Desmoglein-2 is overexpressed in non-small cell lung cancer tissues and its knockdown suppresses NSCLC growth by regulation of p27 and CDK2.

PURPOSE: Desmoglein-2 (Dsg2) is a cell adhesion protein of the cadherin superfamily. Altered Dsg2 expression is associated with tumorigenesis. This study determined Dsg2 expression in non-small cell lung cancer (NSCLC) tissue specimens for association with clinicopathological and survival data and then assessed the effect of Dsg2 knockdown on regulation of NSCLC cell malignant behaviors in vitro and in nude mouse xenografts. METHODS: qRT-PCR and Western blot were used to detect Dsg2 expression in 28 paired NSCLC and normal tissue samples. Immunohistochemistry was used to detect Dsg2 expression in 70 cases of paraffin-embedded NSCLC tissues. NSCLC A549, H1703, and H1299 cells were cultured with Dsg2 knockdown performed using Dsg2 siRNA. Cell viability, cell cycle, apoptosis, and colony formation were assessed. siRNA-transfected A549 cells were also used to generate tumor xenografts in nude mice. RESULTS: Both Dsg2 mRNA and protein were highly expressed in NSCLC tissues and associated with NSCLC size, but not with overall survival of patients. Moreover, knockdown of Dsg2 expression reduced NSCLC cell proliferation and arrested them at the G1 phase of the cell cycle, but did not significantly affect NSCLC cell apoptosis. Dsg2 knockdown downregulated cyclin-dependent kinase 2 expression and upregulated p27 expression. Nude mouse xenograft assays showed that Dsg2 knockdown inhibited NSCLC xenograft growth in vivo. CONCLUSION: This study revealed the importance of Dsg2 in suppression of NSCLC development and progression. Further studies will explore whether restoration of Dsg2 expression is a novel strategy in control of NSCLC.

Influence of clinical practice on nursing students' mental and immune-endocrine functions.

This work aims to evaluate the stressful effects of clinical learning environments on nursing students and to better understand the importance of reducing anxiety. Ninety-two female nursing students were randomly recruited. State Anxiety Inventory (SAI), General Self-Efficacy scale (GSES), Social Support Rating Scale (SSRS), General Maladjustment Scale (GM), Pittsburgh Sleep Quality Index, the personal information questionnaire were administered along with an immune-endocrine profile, red blood cells and plasma cortisol. The nursing students' state and trait anxiety scores were significantly higher in clinic than in school. With one-way ANOVA, nursing students from rural areas, not liking nurse work and being pessimistic to employment prospects, and not being assigned in an ideal teaching hospital had higher scores of SAI. High levels of anxiety were associated with low scores of GSES, objective support of SSRS and high scores of GM. Additionally, the subjects' anxiety related to poor sleep quality, and students with high levels of anxiety showed a significantly lower percentage of CD3 and CD4. In conclusion, clinical practice can raise nursing students' State-Trait Anxiety Inventory scores. The level of anxiety is related to some internal and external factors. Severe anxiety not only affects student's physical and mental health and successful practice, but also reduces T lymphocyte immune functions.