Annals of clinical and laboratory science最新文献

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.

Objective: To present the case of a solid organ transplant recipient with a rash, which might be a drug allergy mimic.

Case report: We present a 62-year-old male lung transplant recipient, who experienced a sudden erythematous rash two months post-transplant after he was given new medications for his transplant status. Physical examination by the team revealed the patient had a generalized flat, polymorphic papular rash with pinpoint crusting and associated excoriations. Skin biopsy indicated purpuric interface dermatitis with eosinophils, which suggested a drug reaction. In the workup process, patient was admitted for Rhinovirus (HRV) infection and placed on 30 mg prednisone tapering. His rash slowly resolved with discontinuation of Bactrim and Voriconazole. His overall clinical picture was concerning for a drug allergy, but he was on high-dose systemic corticosteroid regimen (Prednisone 40 mg daily) which hindered drug allergy testing.

Conclusion: Findings suggest a potential drug allergy or drug reaction, but workup was limited. Thus, the consulting clinician could consider this case a drug allergy mimic or should consider other medical conditions. Challenges exist in identifying a correct differential diagnosis of drug allergy in clinically complicated transplant patients; misdiagnosis may occur, which might lead to delayed care. There is a need for alternative differential diagnostic strategies and treatment options.

Objective: LIN28B and insulin-like growth factor-1 receptor (IGF-1R) play important roles in the growth and metastasis of colorectal cancer (CRC). The relationship between LIN28B and IGF-1R and their co-expression role in CRC is unknown. This study aims to assess whether the combined detection of LIN28B and IGF-1R is a better predictor of prognosis in CRC than either marker alone.

Methods: We used immunohistochemistry to detect LIN28B and IGF-1R protein. The correlation between LIN28B and IGF-1R expression in CRC was determined by the Spearman correlation analysis. The association between LIN28B/IGF-1R expression and clinicopathological features was analyzed, and overall survivals were also performed.

Results: The expression of LIN28B and IGF-1R in CRC tissues were significantly higher than that in non-cancerous tissues (P<0.001 and P<0.001, respectively). LIN28B over-expression positively correlated with IGF-1R over-expression (r=0.283, P=0.007). The increased expression of LIN28B and IGF-1R were both significantly correlated with TNM stage, lymph node metastasis and distant metastasis (all P<0.05). IGF-1R, not LIN28B, was significantly associated with vascular invasion (P=0.007). Overall survival appears to be lower in patients with high LIN28B expression or/and high IGF-1R expression than those with low LIN28B expression or/and low IGF-1R expression. In addition, the predictive sensitivity of LIN28B combined with IGF-1R was stronger than that of either one alone.

Conclusions: The combined over-expression of LIN28B and IGF-1R in patients with colorectal cancer may provide a more powerful predictor for CRC prognosis.