76088 research outputs found
Sort by
RUNX2 stabilization by long non-coding RNAs contributes to hypertrophic changes in human chondrocytes
Get PDFBackground: Chondrocyte hypertrophy has been implicated in endochondral ossification and osteoarthritis (OA). In OA, hypertrophic chondrocytes contribute to the destruction and focal calcification of the joint cartilage. Although studies in this field have remarkably developed the modulation of joint inflammation using gene therapy and regeneration of damaged articular cartilage using cell therapy, studies that can modulate or prevent hypertrophic changes in articular chondrocytes are still lacking. Methods: In vitro hypertrophic differentiation and inflammation assays were conducted using human normal chondrocyte cell lines, TC28a2 cells. Human cartilage tissues and primary articular chondrocytes were obtained from OA patients undergoing total knee arthroplasty. Long non-coding RNAs (lncRNAs), LINC02035 and LOC100130207, were selected through RNA-sequencing analysis using RNAs extracted from TC28a2 cells cultured in hypertrophic medium. The regulatory mechanism was evaluated using western blotting, real-time quantitative polymerase chain reaction, osteocalcin reporter assay, RNA-immunoprecipitation (RNA-IP), RNA-in situ hybridization, and IP. Results: LncRNAs are crucial regulators of various biological processes. In this study, we identified two important lncRNAs, LINC02035 and LOC100130207, which play important roles in hypertrophic changes in normal chondrocytes, through RNA sequencing. Interestingly, the expression level of RUNX2, a master regulator of chondrocyte hypertrophy, was regulated at the post-translational level during hypertrophic differentiation of the normal human chondrocyte cell line, TC28a2. RNA-immunoprecipitation proved the potential interaction between RUNX2 protein and both lncRNAs. Knockdown (KD) of LINC02035 or LOC100130207 promoted ubiquitin-mediated proteasomal degradation of RUNX2 and prevented hypertrophic differentiation of normal chondrocyte cell lines, whereas overexpression of both lncRNAs stabilized RUNX2 protein and generated hypertrophic changes. Furthermore, the KD of the two lncRNAs mitigated the destruction of important cartilage matrix proteins, COL2A1 and ACAN, by hypertrophic differentiation or inflammatory conditions. We also confirmed that the phenotypic changes raised by the two lncRNAs could be rescued by modulating RUNX2 expression. In addition, the KD of these two lncRNAs suppressed hypertrophic changes during chondrogenic differentiation of mesenchymal stem cells. Conclusion: Therefore, this study suggests that LINC02035 and LOC100130207 contribute to hypertrophic changes in normal chondrocytes by regulating RUNX2, suggesting that these two novel lncRNAs could be potential therapeutic targets for delaying or preventing OA development, especially for preventing chondrocyte hypertrophy.ope
Nurse Managers' Leadership, Patient Safety, and Quality of Care: A Systematic Review
No full textThis review examined relationships between nurse unit managers' leadership and patient safety and quality of care outcomes in hospital settings. Employing four databases (CINAHL, Embase, PubMed, and Web of Science) and ancestry searches, we identified 14 English-language, peer-reviewed, primary studies that examined such relationships using quantitative analyses. The studies were published between 2012 and 2021, and most used a cross-sectional design. Each study's quality was assessed using the Mixed-Method Appraisal Tool. In synthesizing results by categorizing outcomes, we found a positive trend in associations between effective nurse unit manager leadership and better outcomes, including fewer patient adverse events, increased nurse error reporting, and higher patient satisfaction and care quality. However, the heterogeneity of leadership measurement approaches and outcomes limited integration of study findings. Future researchers should clearly define study concepts to support interpretation of their findings and should use a suitable theoretical framework to help determine appropriate units of analysis.restrictio
Fusobacterium nucleatum induces a tumor microenvironment with diminished adaptive immunity against colorectal cancers
Get PDFBackground & Aims: Fusobacterium nucleatum (FN) plays a pivotal role in the development and progression of colorectal cancer by modulating antitumor immune responses. However, the impact of FN on immune regulation in the tumor microenvironment has not been fully elucidated.
Methods: The abundance of FN was measured in 99 stage III CRC tumor tissues using quantitative polymerase chain reaction. Gene expression profiles were assessed and annotated using consensus molecular subtypes (CMS), Gene Ontology (GO) analysis, and deconvolution of individual immune cell types in the context of FN abundance. Immune profiling for tumor infiltrating T cells isolated from human tumor tissues was analyzed using flow cytometry. Ex vivo tumor-infiltrating T cells were stimulated in the presence or absence of FN to determine the direct effects of FN on immune cell phenotypes.
Results: Gene expression profiles, CMS composition, abundance of immune cell subtypes, and survival outcomes differed depending on FN infection. We found that FN infection was associated with poorer disease-free survival and overall survival in stage III CRC patients. FN infection was associated with T cell depletion and enrichment of exhausted CD8+ and FoxP3+ regulatory T cells in the tumor microenvironment. The presence of FN in tumors was correlated with a suppressive tumor microenvironment in a T cell-dependent manner.
Conclusion: FN enhanced the suppressive immune microenvironment with high depletion of CD8+ T cells and enrichment of FoxP3+ regulatory T cells in human colorectal cancer cases. Our findings suggest a potential association for FN in adaptive immunity, with biological and prognostic implications.ope
Plasma Antiretinal Autoantibody Profiling and Diagnostic Efficacy in Patients With Autoimmune Retinopathy
No full textPurpose: To evaluate plasma antiretinal autoantibody (ARA) profiling and diagnostic efficacy for autoimmune retinopathy (AIR).
Design: A multicenter, diagnostic evaluation study.
Methods: Forty-nine patients with a clinical diagnosis of AIR, disease controls including 20 patients with retinitis pigmentosa (RP), and 30 normal controls were included. Plasma samples from patients were analyzed for the presence of 6 ARAs, including recoverin, α-enolase, carbonic anhydrase II, heat shock protein 60, aldolase C, and cone-rod homeobox/cone-rod retinal dystrophy 2 using western blotting.
Results: Autoantibody detection rates against cone-rod homeobox/cone-rod retinal dystrophy 2, heat shock protein 60, and aldolase C in AIR were 67.3%, 40.8%, and 42.9%, respectively, which were higher than those in RP and normal controls (P < .001, P < .001, and P = .007, respectively), but recoverin, α-enolase, and carbonic anhydrase II were not different from other control groups (P = .117, P = .774, and P = .467, respectively). Among ARAs, antirecoverin antibody was the most specific, as it was found in 3 (6.1%) patients with AIR and none of the control groups. As the number of detected ARAs increased, the probability of AIR increased (odds ratio: 1.913; P < .001; 95% confidence interval: 1.456-2.785). The positive number of ARAs was significantly higher when photoreceptor disruption was observed on optical coherence tomography, or severe dysfunction was observed in electroretinography (P = .022 and P = .029, respectively).
Conclusions: The profiles of ARAs in the AIR group were different from those in the RP and normal controls. The higher number of positive ARAs suggests a higher possibility of AIR diagnosis. ARAs should be used as adjunct tools for the clinical diagnosis of AIR.restrictio
Subgrouping patients with zoster-associated pain according to sensory symptom profiles: A cluster analysis
Get PDFBackground and goal of study: Patients with zoster-associated pain exhibit a variety of sensory symptoms and forms of pain and complain of different pain patterns. The purpose of this study is to subgroup patients with zoster-associated pain who visited a hospital using painDETECT sensory symptom scores, analyze their respective characteristics and pain-related data, and compare similarities and differences among the groups.
Materials and methods: The characteristics of 1,050 patients complaining of zoster-associated pain and pain-related data were reviewed retrospectively. To identify subgroups of patients with zoster-associated pain according to sensory symptom profiles, a hierarchical cluster analysis was performed based on the responses to a painDETECT questionnaire. Demographics and pain-related data were compared among all subgroups.
Results and discussion: Patients with zoster-associated pain were classified into 5 subgroups according to the distribution of sensory profiles, with each subgroup exhibiting distinct differences in the expression of sensory symptoms. Patients in cluster 1 complained of burning sensations, allodynia, and thermal sensitivity, but felt numbness less strongly. Cluster 2 and 3 patients complained of burning sensations and electric shock-like pain, respectively. Cluster 4 patients complained of most sensory symptoms at similar intensities and reported relatively strong prickling pain. Cluster 5 patients suffered from both burning and shock-like pains. Patient ages and the prevalence of cardiovascular disease were significantly lower in cluster 1. Patients in clusters 1 and 4 reported longer pain duration compared with those in clusters 2 and 3. However, no significant differences were found with respect to sex, body mass index, diabetes mellitus, mental health problems, and sleep disturbance. Pain scores, distribution of dermatomes and gabapentinoid use were also similar among the groups.
Conclusions: Five different subgroups of patients with zoster-associated pain were identified on the basis of sensory symptoms. A subgroup of younger patients with longer pain duration showed specific and distinct symptoms, such as burning sensations and allodynia. Unlike patients with acute or subacute pain, patients with chronic pain were associated with diverse sensory symptom profiles.ope
The relationship between depression, self-efficacy, social support, and health-promoting behaviors in Korean single-household women
Get PDFThis descriptive, cross-sectional study purposed to identify the relationship between depression, self-efficacy, social support, and health-promoting behaviors in adult single-household women in Korea. An online survey was completed by 204 adult single-household women in Korea from November to December 2019. The structured questionnaire included items measuring depression, health-related self-efficacy, social support, health-promoting behaviors, and demographic and health-related characteristics. Descriptive statistics were computed, and mediation, moderation, and moderated mediation analyses were conducted. The average age of the participants was 34.38, and the average duration of living alone was 7.13 years. The health-promoting behavior of single-household women scored 125.85 in average within the possible score range of 52-208. It was verified that social support has a moderated mediating effect that regulates the mediating effect in the pathway by which depression affects health-promoting behaviors through self-efficacy. In conclusion, self-efficacy was found to play a mediating role between depression and health-promoting behaviors, and social support had a moderated mediating effect on the path from depression to health-promoting behaviors through self-efficacy. To encourage the health-promoting behaviors of single-household women, interventions targeting both increased social support and self-efficacy are suggested.ope
High-Dose Selenium Induces Ferroptotic Cell Death in Ovarian Cancer
Get PDFSelenium is a promising multi-target chemotherapeutic agent with controversial clinical results. Hence, reassessing the anticancer effects of Se is necessary to clearly understand the potential of high-dose selenium in cancer treatment. Here, we observed that high-dose sodium selenite (SS) significantly decreased the proliferation and increased the death of ovarian cancer cells, mediated by an increased generation of reactive oxygen species. Notably, high-dose SS decreased the levels of glutathione peroxidase (GPx), a selenoprotein with antioxidant properties, without altering other selenoproteins. Furthermore, high-dose SS triggered lipid peroxidation and ferroptosis, a type of iron-dependent cell death, due to dysregulated GPx4 pathways. We demonstrated that intravenous high-dose SS significantly reduced the tumor growth and weight in SKOV3-bearing mice. Consistent with our in vitro results, mice with SKOV3 cells treated with high-dose SS showed decreased GPx4 expression in tumors. Therefore, we highlight the significance of high-dose SS as a potential chemotherapeutic agent for ovarian cancer. High-dose SS-mediated ferroptotic therapy integrating glutathione depletion and ROS generation is a promising strategy for cancer therapy.ope
Left Atrial Velocity Vector Imaging Can Assess Early Diastolic Dysfunction in Left Ventricular Hypertrophy and Hypertrophic Cardiomyopathy
Get PDFBackground: The function of left atrium (LA) is difficult to assess because of its ventricle-dependent, dynamic movement. The aim of this study was to assess LA function using velocity vector imaging (VVI) and compare LA function in patients with hypertrophic cardiomyopathy (HCMP) and left ventricular hypertrophy (LVH) with normal controls.
Methods: Fourteen patients with HCMP (72% male, mean age of 52.6 ± 9.8), 15 hypertensive patients with LVH (88% male, mean age of 54.0 ± 15.3), and 10 age-matched controls (83% male, mean age of 50.0 ± 4.6) were prospectively studied. Echocardiographic images of the LA were analyzed with VVI, and strain rate (SR) was compared among the 3 groups.
Results: The e' velocity (7.7 ± 1.1; 5.1 ± 0.8; 4.5 ± 1.3 cm/sec, p = 0.013), E/e' (6.8 ± 1.6; 12.4 ± 3.3; 14.7 ± 4.2, p = 0.035), and late diastolic SR at mid LA (-1.65 ± 0.51; -0.97 ± 0.55; -0.82 ± 0.32, p = 0.002) were significantly different among the groups (normal; LVH; HCMP, respectively). The e' velocity, E/e', and late diastolic SR at mid LA were significantly different between normal and LVH (p = 0.001; 0.022; 0.018), whereas LA size was similar between normal and LVH (p = 0.592). The mean late diastolic peak SR of mid LA was significantly correlated with indices of diastolic function (E/e', e', and LA size).
Conclusions: The SR is a useful tool for detailed evaluation of LA function, especially early dysfunction of LA in groups with normal LA size.ope
Comparing the efficacy of different methods of faecal microbiota transplantation via oral capsule, oesophagogastroduodenoscopy, colonoscopy, or gastric tube
No full textBackground: The increasing prevalence of multidrug-resistant organism (MDRO) carriage poses major challenges to medicine as healthcare costs increase. Recently, faecal microbiota transplantation (FMT) has been discussed as a novel and effective method for decolonizing MDRO.
Aim: To compare the efficacy of different FMT methods to optimize the success rate of decolonization in patients with MDRO carriage.
Methods: This prospective cohort study enrolled patients with MDRO carriages from 2018 to 2021. Patients underwent FMT via one of the following methods: oral capsule, oesophagogastroduodenoscopy (EGD), colonoscopy, or gastric tube.
Findings: A total of 57 patients underwent FMT for MDRO decolonization. The colonoscopy group required the shortest time for decolonization, whereas the EGD group required the longest (24.9 vs 190.4 days, P = 0.022). The decolonization rate in the oral capsule group was comparable to that in the EGD group (84.6% vs 85.7%, P = 0.730). An important clinical factor associated with decolonization failure was antibiotic use after FMT (odds ratio = 6.810, P = 0.008). All four groups showed reduced proportions of MDRO species in microbiome analysis after FMT.
Conclusion: Compared to other conventional methods, the oral capsule is an effective FMT method for patients who can tolerate an oral diet. The discontinuation of antibiotics after FMT is a key factor in the success of decolonization.restrictio
