International Journal of Medical Sciences最新文献

Objectives: This study aimed to investigate the involvement of macrophage ferroptosis in chronic apical periodontitis (CAP) and determine if blocking JNK/JUN/NCOA4 axis could alleviate CAP by regulating macrophage ferroptosis. Materials and Methods: Firstly, the in vitro models of apical periodontitis (AP) and in vivo models of CAP, including clinical specimens and rats' periapical lesions, were utilized to investigate the role of macrophage ferroptosis in CAP by detecting the ferroptosis related factors. The activation of the JNK/JUN/NCOA4 axis was observed in CAP in vivo models. Pearson's correlation and linear tendency tests were employed to analyze the correlation between the JNK/JUN/NCOA4 axis and macrophage ferroptosis during CAP progression. Subsequently, the JNK/JUN/NCOA4 axis was blocked by SP600125, and the alterations in ferroptosis associated variables and inflammation levels in macrophages were evaluated. Results: The in vitro AP model demonstrated that macrophage ferroptosis mainly occurred during the late phase of inflammatory conditions, with the reduction of GPX4, SLC7A11 and the increase of TFR1 in macrophages. Additionally, a higher accumulation of iron was observed in the periapical lesions derived from clinic samples and animal model. Furthermore, we found that differences in macrophage ferroptosis levels within periapical lesions corresponded altered activation of JNK/JUN/NCOA4 axis. Significantly, the inhibition of JNK/JUN/NCOA4 axis reduced the aforementioned changes and inflammation levels induced by E. coli LPS in macrophages. Conclusions: The occurrence of ferroptosis in macrophages contributes to the development of CAP. Targeting the JNK/JUN/NCOA4 axis is an effective therapeutic strategy to rescue the periapical lesions from inflammation due to its anti-macrophage ferroptosis function. Consequently, the current study provides support for further investigation on the JNK/JUN/NCOA4 axis as a targeted signaling pathway for CAP treatment.

Background: The roles of Forkhead box N1 (FOXN1) in lung squamous cell carcinoma (LUSC) remains elusive. This study was focused on assessing the expression levels of FOXN1 in LUSC and exploring its potential clinical implications. Methods: Utilizing a range of databases, this study conducted an analysis of the FOXN1 gene's expression levels, comparing LUSC samples with those from normal lung tissues. The expression levels of FOXN1 in primary LUSC and corresponding normal lung tissues were assessed using immunohistochemistry (IHC). Histoscore was used to evaluate the staining degree. χ2 test and Fisher's exact test were employed to assess the association between categorical variables that do not possess an ordinal nature. Multivariate survival analysis was conducted using the Kaplan-Meier method, the Wilcoxon test, and the Cox proportional hazards model. Results: In contrast to normal lung tissues, the expression of the FOXN1 gene was found to be significantly elevated in LUSC tissues (P < 0.01). And FOXN1 was expressed in 79 (98.8%) evaluated LUSC tissues, most of which showed compositive IHC-staining intensity, presenting heterogeneously expression. 69 (87.3%) cases were characterized for strong immunostaining intensity, 70 (87.5%) cases showed moderate intensity, and 66 (82.5%) cases presented weak intensity. Only one sample of normal lung tissue, which represents 10% of the total, exhibited weak immunostaining exclusively (P < 0.05). Additionally, the expression of FOXN1 was found to have a significant correlation with the grading of LUSC, the presence of lymph node and distant metastases, the stage of the disease, and the survival outcomes (P < 0.05). Conclusion: The expression of FOXN1 is frequently increased in LUSC, and the patients with high FOXN1 expression have a poorer survival outcome. FOXN1 can be a novel biomarker and prognostic indicator for LUSC patients.

Background: Sepsis is a lethal disease due to uncontrolled inflammatory responses. Macrophages play an important role in sepsis-associated inflammation. Jing Si Herbal Tea (JSHT) is a plant-based regimen with anti-inflammatory properties designed to treat respiratory diseases; however, its underlying therapeutic mechanism remains unclear. This study aimed to investigate the effects of JSHT on macrophage polarization and inflammatory signaling in lipopolysaccharide (LPS)-induced inflammation to provide therapeutic approaches for inflammatory diseases. Methods: RAW264.7 cells were stimulated with LPS (1 µg/mL for 16 h) to induce inflammatory responses and treated by JSHT (0.0125% concentration for 4 h) in the experimental groups (Control, JSHT, LPS, Pre-JSHT, and Post-JSHT groups). We investigated the protein and cytokine expression levels using western blotting and enzyme-linked immunosorbent assay (ELISA). Macrophage morphology was observed using immunofluorescence staining. The polarization surface markers were detected by flow cytometry. Results: In the LPS group, the expressions of the inflammatory signaling (pERK, pJNK, and nuclear NFκB) and the pro-inflammatory cytokine levels (TNF-α, IL-1β, and IL-6) were significantly increased, with M1 polarization (CD68+/CD80+) compared to the Control group. In the Pre-JSHT and Post-JSHT groups, the expressions of the inflammatory signaling and the pro-inflammatory cytokine levels were significantly decreased, with a higher M2 polarization ratio (CD163+/CD206+) compared to the LPS group. RAW264.7 cells exhibited filopodia protruding from the cell surface in the LPS group, which were inhibited in the Pre-JSHT and Post-JSHT groups. Conclusions: LPS induced M1 polarization with elevated inflammatory signaling and cytokine levels, while JSHT not only decreased M1 polarization but also promoted M2 polarization with decreased inflammatory responses. We propose JSHT as a potential anti-inflammatory agent against LPS-induced inflammation.

Background: Urinary incontinence (UI) and erectile dysfunction (ED) often arise as frequent postoperative complications following robotic-assisted radical prostatectomy (RARP) for prostate cancer (PCa). These issues can significantly diminish patients' quality of life (QoL). The assessment of QoL is even more important because treatment decisions may be influenced by the expected QoL. Few studies have integrated the clinical profiles of patients with magnetic resonance imaging (MRI) metrics to assess postoperative UI and ED. Methods: PCa patients treated with RARP between January 2018 and September 2022 were enrolled in this study. Preoperative clinical baseline characteristics and MRI parameters were retrospectively collected. The Expanded Prostate Cancer Index Composite Short Form (EPIC-26) questionnaire was completed to assess urinary continence and sexual function at regular postoperative follow-up. Preoperative baseline clinical characteristics and MRI parameters were subsequently used to screen for predictors of urinary continence and sexual function after RARP, and predictive models were constructed. Results: A total of 627 patients with PCa who met the criteria were ultimately included in this study, with 1059 follow-up questionnaires. The predictive model for postoperative urinary continence was constructed with respect to age, history of transurethral resection of the prostate (TURP) surgery, clinical T stage (cT), Gleason score (GS), Charlson score, membranous urethral length (MUL), pubic symphysis-prostate apex length (PAL), urethral width, right anal sphincter thickness and anal levator muscle thickness (axial plane). Moreover, body mass index (BMI), cT, age, GS, Charlson score, internal obturator muscle thickness, urethral width and anal sphincter thickness were predictors of short-term and long-term postoperative sexual function. We were able to develop highly effective predictive models for postoperative urinary continence and sexual function in RARP patients by incorporating baseline clinical features and MRI parameters. Conclusions: The predictive model enables the assessment of postoperative urinary continence and sexual function in patients after RARP and offers clinical guidance.

This study aimed to evaluate the clinical outcomes of patients diagnosed with acute severe hepatitis B (ASHB) who received early antiviral therapy compared to those who did not. Patients diagnosed with acute hepatitis B between February 2019 and February 2023 at our hospital were retrospectively analyzed for admission characteristics, antiviral treatments, and serum HBsAg and anti-HBs levels over 3-6-12 months. Acute severe hepatitis B was defined as serum total bilirubin > 5 mg or INR > 1.5. Of the 57 patients included, 26.3% (n=15) were female, and the median age was 40.2 (21-90) years. Within 48 hours of admission, 2 patients had concurrent diseases (3%) died. Two patients with concurrent HIV diagnosis were excluded. Treatment was initiated in 27 of 53 ASHB patients (entecavir/tenofovir: 24/3). One patient in the treatment group underwent liver transplantation due to fulminant hepatitis, and another patient died while on the waiting list. Long-term follow-up information for 3 patients in the untreated group was unavailable. The study continued with 25 treated and 23 untreated patients. No significant differences were observed in age, ALT levels, albumin, leukocyte, neutrophil, and platelet levels between the two groups (respectively; p = 0.57, p = 0.071, p = 0.187, p = 0.46, p = 0.94, p = 0.307). However, in the treated group, AST, total bilirubin, INR, and hospitalization duration were higher, and lymphopenia was more common. In the entire patient population, HBsAg seroclearance rates were 54% at 3 months (69% in treated vs. 34% in untreated; p = 0.127), 83.3% at 6 months (95% in treated vs. 74% in untreated; p = 0.218), and 100% at 12 months. Early antiviral therapy did not show an association with chronicity in ASHB patients. Conducting randomized controlled studies with a larger patient population is necessary to provide a definitive conclusion on initiating early antiviral therapy. However, such studies pose ethical challenges.

Background: This study aims to investigate the effectiveness of lasers at various wavelengths in treating medication-related osteonecrosis of the jaw (MRONJ) using biochemical, clinical scoring, micro CT analysis, and histopathological methods. The study follows the ARRIVE guidelines to ensure robust and transparent research. Methods: In our study, there were 6 groups, including one SHAM group, one CONTROL group, and four experimental groups, with 8 rats in each individual group. Each rat received antiresorptive drug intraperitoneally for 4 weeks and then had the left second molar in the mandible extracted. All animals were sacrificed at the end of the 12th week. In the experimental groups, lasers at wavelengths of 405nm, 445nm, 660nm, and 808nm were applied to the animals. Parameters such as serum vitamin D levels, bone density and bone volume at the extraction site, new bone formation, dead bone count, inflammatory cell count, and epithelial regeneration were examined. Additionally, clinical scoring was conducted after sacrifice. The laser parameters included power density, area, time, fluence, and mode (continuous wave), and the light was administered using a fiber with a Gaussian profile. Statistical analyses were performed with the NCSS (Number Cruncher Statistical System) 2007 Statistical Software (Utah, USA) package program. The results were evaluated at the p<0.05 significance level. Results: According to the results obtained from our study, new bone formation in all experimental groups was significantly higher than in the SHAM and CONTROL groups. Furthermore, the 660nm and 808nm wavelengths increased serum vitamin D levels significantly. The most successful outcomes were observed in clinical scoring, dead bone count, epithelial cell regeneration, and bone density in the 660nm and 808nm wavelength groups. Conclusions: The combined use of lasers at 660nm and 808nm wavelengths may yield successful results in treating MRONJ.

Solute carrier 41 (SLC41) has been identified as a family of magnesium (Mg²⁺) transporters that participate in various diseases, including tumor development and progression. Recent studies revealed SLC41A3 acted as an oncogene and predicted poor survival for hepatocellular carcinoma (HCC) patients. However, the potential function of SLC41A1 in HCC remains unclear. In our study, we focused on the levels and putative mechanisms of SLC41A1 in HCC. Using bioinformatics techniques, we found SLC41A1 was upregulated in HCC, which was verified by immunostaining of HCC patients. SLC41A1 was correlated with clinicopathological characteristics, and could be utilized as independently diagnostic and prognostic markers for HCC. By exploring MethSurv website, DNA methylation was identified in SLC41A1, and several methylated CpG sites might affect overall survival of HCC patients. Using Gene Ontology (GO) , Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), protein-protein interaction (PPI) network, we found SLC41A1 overexpression was related to several tumor-promoting pathways and molecules, such as degradation of extracellular matrix, cell adhesion and O-linked glycosylation, and expression of CXCL1, CXCL5 and MUC1. The results of single-sample GSEA (ssGSEA) showed SLC41A1 might regulate infiltration of multiple immune cells, resulting in the imbalance between immune suppression and immune surveillance. Cellular experiments showed that knockdown of SLC41A1 inhibited proliferation, migration and invasion of HCC, whereas SLC41A1 overexpression exerted the tumor-promoting effects. Collectively, our results shed light on new insights into expression, putative roles and mechanisms of SLC41A1 in HCC, providing novel diagnostic biomarkers and therapeutic targets for HCC.

Background/Purpose: The burden and epidemiology of Mycoplasma pneumoniae (Mp) community-acquired pneumonia (CAP) among hospitalized U. S. adults (≥ 18 years) are poorly understood. Methods: In the Etiology of Pneumonia in the Community (EPIC) study, we prospectively enrolled 2272 adults hospitalized with radiographically-confirmed pneumonia between January 2010-June 2012 and tested nasopharyngeal/oropharyngeal swabs for Mp by real-time polymerase chain reaction (PCR). Clinical and epidemiological features of Mp-PCR-positive and -negative adults were compared using logistic regression. Macrolide susceptibility was assessed by genotyping isolates. Results: Among 2272 adults, 43 (1.8%) were Mp-PCR-positive (median age: 45 years); 52% were male, and 56% were non-Hispanic white. Only one patient had Mp macrolide resistance. Four (9%) were admitted to the intensive care unit (ICU). No in-hospital deaths were reported. Of the 9 (21%) who received an outpatient antibiotic ≤5 days pre-admission, 2 (22%) received an antibiotic with Mp activity. Variables significantly associated with higher odds of Mp detection included age {18-29 years [(adjusted odds ratio (aOR): 11.7 (95% confidence interval (CI): 5.1- 26.6) versus ≥50 years]} and radiographic lymphadenopathy [aOR: 3.5 (95% CI: 1.2- 9.3)]. Conclusions: M. pneumoniae, commonly known to cause "walking pneumonia", was detected among hospitalized adults, with the highest prevalence among young adults. Although associated with clinically non-specific symptoms, approximately one out of every ten patients were admitted to the ICU. Increasing access to M. pneumoniae point-of-care testing could facilitate targeted treatment and avoid hospitalization.

Background: The mechanisms of gastric cancer (GC) occurrence and development are still unclear. Although glycosyltransferase 8 domain containing 1 (GLT8D1) has been implicated in GC, its specific role and molecular mechanisms in GC progression need to be further investigated. Methods: Tissue microarrays were used to detect the expression levels of GLT8D1 in 80 GC tissues and their corresponding non-tumor adjacent tissues. The correlations between the GLT8D1 expression level and clinicopathological characteristics were evaluated. A series of in vitro and in vivo functional experiments were performed to explore the role of GLT8D1 in GC progression. Combined with transcriptomic RNA sequencing (RNA-seq) and Weighted Gene Co-expression Network Analysis (WGCNA), we delineated the potential mechanisms via experimental verification. Results: Elevated expression of GLT8D1 in GC tissues was positively correlated with advanced clinical stages and poor prognosis. Konckdown of GLT8D1 significantly inhibited GC cell proliferation and induced apoptosis, whereas overexpression did the opposite. Further researches demonstrated that protein tyrosine phosphatase non-receptor type 6 (PTPN6), a downstream target of GLT8D1, has the capacity to modulate the activity of the JAK2/STAT3 signaling pathway. Conclusions: Our study indicated that GLT8D1 expression was upregulated in GC tissues and correlated with poor prognosis. We reveal a potential molecular mechanism by which GLT8D1 promotes GC progression.