An immune biomarker associated with EMT serves as a predictor for prognosis and drug response in bladder cancer.

BACKGROUND: Bladder cancer (BLCA), which develops from the upper endometrial of the bladder, is the sixth most prevalent cancer across the globe. WDHD1 (WD repeat and HMG-box DNA binding protein 1 gene) directly affects signaling, the cell cycle, and the development of the cell skeleton. Uncertainty surrounds WDHD1's function in BLCA immunity and prognosis, though. MATERIALS AND METHODS: Using weighed gene co-expression network analysis (WGCNA), initially, we first identified 32 risk factors in genes with differential expression for this investigation. Then, using a variety of bioinformatic techniques and experimental validation, we examined the connections between WDHD1 and BLCA expression, clinical pathological traits, WDHD1-related proteins, upper-skin-intermediate conversion (EMT), immune cell immersion, convergence factors, immune markers, and drug sensitivity. RESULT: The findings demonstrated that we constructed a 32-gene risk-predicting model where WDHD1 was elevated as a representative gene expression in BLCA and related to a range of clinical traits. Furthermore, high WDHD1 expression was a standalone predictor associated with a worse survival rate. The most commonly recruited cells and their evolutionary patterns were highlighted to better comprehend WDHD1's function in cancer. High WDHD1 expression was associated with many aspects of immunology. Finally, the study found that individuals with high expression of WDHD1 were drug-sensitive to four different broad-spectrum anti-cancer drugs. CONCLUSION: These results describe dynamic changes in the tumor microenvironment in BLCA and provide evidence for the hypothesis that WDHD1 is a novel biomarker of tumor development. WDHD1 may therefore be a useful target for the detection and management of BLCA.

Diagnostic Performance of Contrast-Enhanced Ultrasound in Testicular Space-Occupying Lesions: A Systematic Review and Meta-analysis.

PURPOSE: Contrast-enhanced ultrasound (CEUS) has been increasingly used for the diagnostic identification of neoplasms due to its ability to visualize the microvascularization of lesions. In the study of testicular abnormalities, the appropriate use of CEUS can improve the diagnostic accuracy of conventional gray-scale ultrasound and color Doppler ultrasound (CDUS). The purpose of this study is to comprehensively evaluate the diagnostic performance of CEUS in testicular space-occupying lesions. METHODS: A comprehensive search of PubMed, Embase, Cochrane Library, and Web of Science databases was conducted from the inception of each database to November 16, 2022 for relevant studies. The required data were extracted, and the methodological quality of the studies was assessed using the QUADAS-2 tool. The diagnostic value of CEUS was assessed by calculating the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio, and a summary receiver operating characteristic (SROC) curve was used to conduct this meta-analysis. RESULTS: A total of six studies with 354 testicular space-occupying lesions were included in the analysis. The results showed that CEUS could provide additional useful information for the diagnosis of testicular space-occupying lesions, with a sensitivity of 0.92 (95% CI:0.82, 0.97), specificity of 0.91 (95% CI:0.80, 0.96), diagnostic odds ratio of 114 (95% CI:25, 528), respectively, and an overall diagnostic accuracy expressed as area under the SROC curve (AUC) of 0.97 (95% CI:0.95-0.98). Significant heterogeneity was seen in the sensitivity with I2 = 82.53% (95% CI:69.44-95.61). Subgroup analysis revealed that the proportion of infertile patients selected may be the source of heterogeneity. CONCLUSION: CEUS can be used to diagnose testicular space-occupying lesions more accurately and improve diagnostic accuracy when the conventional US cannot accurately differentiate the type of lesion. In particular, CEUS should be recommended for the identification of microscopic lesions so that physicians can provide patients with more appropriate interventions to avoid unnecessary orchiectomy.

SPAG5 deficiency activates autophagy to reduce atherosclerotic plaque formation in ApoE-/- mice.

BACKGROUND: Autophagy, as a regulator of cell survival, plays an important role in atherosclerosis (AS). Sperm associated antigen 5 (SPAG5) is closely associated with the classical autophagy pathway, PI3K/Akt/mTOR signaling pathway. This work attempted to investigate whether SPAG5 can affect AS development by regulating autophagy. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with oxidized-low density lipoprotein (ox-LDL) to induce cell damage. ApoE-/- mice were fed a Western diet to establish an AS mouse model. Haematoxylin and eosin (H&E) staining and Oil Red O staining evaluated the pathological changes and in lipid deposition in aortic tissues. CCK-8 and flow cytometry detected cell proliferation and apoptosis. Immunohistochemistry, Enzyme linked immunosorbent assay, qRT-PCR and western blotting assessed the levels of mRNA and proteins. RESULTS: Ox-LDL treatment elevated SPAG5 expression and the expression of autophagy-related proteins, LC3-I, LC3-II, Beclin-1, and p62, in HUVECs. GFP-LC3 dots were increased in ox-LDL-treated HUVECs and LPS-treated HUVECs. SPAG5 knockdown reversed both ox-LDL and LPS treatment-mediated inhibition of cell proliferation and promotion of apoptosis in HUVECs. SPAG5 silencing further elevated autophagy and repressed the expression of PI3K, p-Akt/Akt, and p-mTOR/mTOR in ox-LDL-treated HUVECs. 3-MA (autophagy inhibitor) treatment reversed SPAG5 silencing-mediated increase of cell proliferation and decrease of apoptosis in ox-LDL-treated HUVECs. In vivo, SPAG5 knockdown reduced atherosclerotic plaques in AS mice through activating autophagy and inhibiting PI3K/Akt/mTOR signaling pathway. CONCLUSION: This work demonstrated that SPAG5 knockdown alleviated AS development through activating autophagy. Thus, SPAG5 may be a potential target for AS therapy.