Annals of clinical and laboratory science最新文献

Objective: Nrf2/ARE signaling pathway is reported to alleviate sleep anxiety in patients with sleep disorders. This study aimed at exploring the effect of escitalopram (ESC) on sleep anxiety in patients with cerebral small vessel disease (CSVD) and sleep disorder and its correlation with the Nrf2/ARE signaling pathway.

Methods: In the present study, we enrolled 80 CSVD patients (disease group) and 40 healthy patients (control group) in our hospital. The CSVD patients were classified into ESC treatment group and conventional treatment group and administered ESC and diazepam, respectively. After treatment, the patients' sleep quality was monitored within three months, and their symptoms were evaluated. Additionally, a mouse model of CSVD was set up, and the rats received intragastric administration of low, moderate, and high dosage of ESC or thymoquinone. The morphology of nerve cells and cognitive functions in the rat hippocampus were seen. TUNEL staining was conducted to detect nerve cell apoptosis and RT-qPCR, and Western blot analyses determined the expression levels of Nrf2 and ARE.

Results: Compared with conventional treatment group, the patients of ESC treatment group had shorter symptom improvement time and better sleep quality with a lower AHI and PSQI score. On the other hand, in the animal model, ESC treatment alleviated sleep disorders in CSVD rats, improved cognition and serum TNF-α levels, and protected nerve cells. Administration of ESC eliminated the expressions of Nrf2 and ARE and reduced nerve cell apoptosis dose-dependently. Moreover, Nrf2/ARE pathway activator (Danshensu) decreased rat sleep time and the level of serum TNF-α with more cell atrophy, while Nrf2/ARE pathway inhibitor (ML385) greatly improved sleep quality of CSVD rats.

Conclusion: ESC can effectively relieve sleep anxiety in patients with CSVD and sleep disorders through downregulating the Nrf2/ARE signaling pathway. ESC treatment increases patient's sleep time and serum TNF-α levels and attenuates nerve cell damage, further improving the patient's sleep quality.

Objective: We studied the role of LNCRNA 1197 in rheumatoid arthritis (RA) and its underlying mechanism.

Methods: We detected expression of LNCRNA 1197 in RA fibroblast-like synovial cells (RA-FLS) by RT-qPCR. Functional experiments were conducted to assess the impact of LNCRNA on cells as demonstrated by a Transwell assay. In addition, Western blot analysis was conducted to analyze the expression of proliferation-related proteins and flow cytometry and CCK-8 to analyze cell cycle and cell proliferation. We also identified the potential downstream target miRNA of LNCRNA 1197.

Results: LNCRNA 1197 was highly expressed in RA-FLS. When LNCRNA 1197 was knocked down, the cell proliferation, migration, and invasion of RA-FLS were alleviated, and pro-inflammatory cytokines were significantly downregulated. Interestingly, LNCRNA 1197 was indicated to target miR-206 and promoted progression of FLS by inhibiting miR-206.

Conclusion: Taken altogether, LNCRNA 1197 promotes the progression of RA-FLSs by miR-206 inhibition.

Objective: Esophageal squamous cell carcinoma (ESCC) is commonly diagnosed with high mortality worldwide. Cell proliferation and cell apoptosis are essential biological processes for the development of cancers. MiR-16-5p, a critical member of miRNAs family, is involved in cell apoptosis and tumor progression. However, the role of miR-16-5p in regulating esophageal squamous cell carcinoma and the underlying mechanism remain unclear.

Methods: In this study, we used human ESCC tissue samples and human esophageal cells to determine the expression level of miR-16-5p in ESCC tissues and cells. Cell Counting Kit-8 assay and flow cytometry were used to test cell proliferation and apoptosis. Western blotting was used to detect protein expression levels. The scratch assay was used to analyze the level of cell migration, and the transwell assay was used to analyze the invasive ability of tumor cells.

Results: The expression of miR-16-5p was up-regulated in ESCC tissues and cells. Knockdown of miR-16-5p significantly inhibited cell proliferation and promoted cell apoptosis. The knockdown of miR-16-5p also restrained cell migration and invasion. We revealed that AMPK/mTOR signaling pathway participated in the regulation of ESCC progression.

Conclusion: miR-16-5p may promote the proliferation, migration, and invasion of ESCC through modulating AMPK/mTOR signaling pathway.

Objective: The purpose of this study is to evaluate the accuracy of Sysmex XN-9000 hematology analyzer (XN-9000) in detecting nucleated cell classifications in serous effusion and to further evaluate whether it can be used for screening malignant serous effusion.

Methods: The consistency between XN-9000 and manual microscopy in the classification of nucleated cells was evaluated using Passing-Bablok regression and Bland-Altman plot. ROC analysis was applied to evaluate the value of HF-BF% in screening malignant specimens.

Results: In the serous effusion of the group with nucleated cell count of (0-150) ×10⁶/μL, high consistency between XN-9000 and manual microscopy was found in detecting NE-BF% and LY-BF%. In the group with nucleated cell count >150×10⁶/μL, there was high consistency in detecting NE-BF%, LY-BF%, and HF-BF%. ROC analysis showed that HF-BF% can be used for screening malignant serous effusion, with an area under the curve (AUC) of 0.572 (95%CI=0.504~0.639).

Conclusion: If XN-9000 detection results are mainly NE-BF% and LY-BF%, the classification can be effectively referred to and reported regardless of the number of nucleated cells in the serous effusion. HF-BF% has certain value in screening malignant serous effusion with a nuclear cell count >150×10⁶/μL. The optimal cut-off value is 13.15%.

Objective: To explore the mechanism for mesoporous silica nano-modified ginsenoside Rh2 promoting tumor immunosuppression in lung cancer through PD-1/PD-L1 pathway.

Methods: Firstly, G-Rh2-MSN were prepared and lung cancer A549 cells were cultured. The following groups were set up to analyze whether G-Rh2-MSN down-regulates PD-1/PD-L1 to promote tumor immunity, inhibit activities of lung cancer cells, and promote apoptosis: Model control group, G-Rh2 group, G-Rh2-MSN group, G-Rh2-MSN+PT001 group, G-Rh2-MSN+nivolumab group, G-Rh2-MSN+Durvalumab group, G-Rh2-MSN+atezolizumab group, and G-Rh2-MSN+nivolumab+Durvalumab group.

Results: G-Rh2-MSN was successfully prepared and found to promote tumor immunity, inhibit the behaviors of lung cancer cells, and accelerate apoptosis. Down-regulation of PD-1/PD-L1 pathway by G-Rh2-MSN can accelerate development of tumor immunosuppressive lung cancer. G-Rh2-MSN promoted tumor immunity by downregulating PD-1/PD-L1, inhibiting activities of lung cancer cells, and promoting apoptosis.

Conclusion: We clarified the mechanism for G-Rh2-MSN in lung cancer A549 cells, showing that it can significantly down-regulate PD-1/PD-L1 signaling, thereby promoting tumor immunity. G-Rh2-MSN modified material inhibits immune escape and reduces behaviors of lung cancer A549 cells by affecting PD-1 and PD-L1 expression, which has potential clinical application prospects.

Objective: Gliomas are common intracranial tumors with high malignancy and poor prognosis, classified into glioblastomas (GBM) and low-grade glioma (LGG). However, the regulatory mechanisms of glioma tumorigenesis remain unclear. This study aimed to investigate the role of six-transmembrane epithelial antigen of the prostate 3 (STEAP3) in glioma prognosis and explore its potential as a therapeutic target, as well as the ferroptosis-related molecular mechanism in progression of gliomas.

Methods: Cox regression analyses were used to identify prognostic factors of gliomas patients from Cancer Genome Atlas (TCGA) database and DESeq2 package was used for differential gene expression comparisons between Grade 2 and Grade 4 gliomas. Wilcoxon rank-sum test was used to compare the STEAP3 expression levels between glioma tissues and normal controls in Xiantao platform, as well as between TCGA glioma samples and GTEx normal samples. A protein-protein interaction (PPI) network was constructed using STRING database information, with hub genes identified through Cytoscape software. Cell viability was determined by MTT assay. Cell proliferation was determined by BrdU incorporation and clone formation assay. GSH and MDA concentration was determined according to kit protocols. The expression of STEAP3, Nrf2, GPX4 was determined by western blotting analysis.

Results: Our results revealed that STEAP3 is overexpressed in glioma tissues compared to normal counterparts and correlates with poor overall survival (OS). High STEAP3 expression significantly correlates with various clinical-pathological features such as age, histological type, treatment response, World Health Organization (WHO) grade, isocitrate dehydrogenase (IDH) status, and survival events. Knockdown STEAP3 inhibited cell proliferation and enhanced erastin-induced ferroptosis in U87 and U138 cells. Moreover, knockdown STEAP3 in glioma cells decreased the GSH levels and increased the production of MDA probably by inhibiting the Nrf2/GPX4 related signaling pathway.

Conclusion: STEAP3 serves as an independent biomarker for glioma prognosis with significant diagnostic value. High STEAP3 expression was correlated with poor overall outcomes of glioma patients. Knockdown of STEAP3 significantly suppressed the proliferation of glioma cells and increased erastin-induced ferroptosis via Nrf2/GPX4 pathway.

Axillary lymph node metastasis (ALNM) is a rare mode of lung cancer (LC) metastasis. We present two LC cases with ALNM, including one case of sarcomatoid carcinoma and one of squamous cell carcinoma. Both cases were diagnosed by positron emission tomography-computed tomography and needle biopsy. A literature review indicates that the most likely route for ALNM from LC is through retrograde diffusion of supraclavicular lymph nodes.

Objective: Oxidative stress is considered to increase fracture risk, and lipid oxidation can adversely affect bone health. 4-hydroxynonenal (4-HNE) is a representative marker of lipid oxidation.

Methods: We investigated the association between 4-HNE and fracture risk in community-dwelling older subjects (n=78, mean age=78 years). Serum albumin, C-reactive protein, and 4-HNE values were examined with the Fracture Risk Assessment Tool (FRAX®). The FRAX® score of >15% was defined as a high fracture risk.

Results: There was a significantly higher 4-HNE value in the group of high fracture risk (n=38, median=12.4 ng/mL) than in the low-risk group (n=40, median=9.8 ng/mL; p=0.02). The correlation of FRAX® major osteoporosis (β=0.45) and FRAX® hip fracture (β=0.44) with 4-HNE was significant after adjustment for multiple variables.

Conclusions: 4-HNE was suggested to be positively associated with fracture risk. This molecule may be a clinical candidate oxidative stress marker for fracture risk in the older population.