Esculetin, the main active ingredient in the Chinese herbal medicineCortex Fraxini, has been shown to possess antitumor activity. However, the effect of esculetin on clear cell renal cell carcinoma (ccRCC) has not been investigated. MTS assays and colony formation assays were used to study the cytotoxicity of esculetin. The effects of esculetin on cell cycle and apoptosis were analyzed by flow cytometry. Western blot was used to detect cell cycle-, apoptosis-, and EMT-related proteins. Wound-healing assays and transwell assays were performed to study the effect of esculetin on cell migration and invasion in the ccRCC cell lines 786-O and SN12-PM6. Esculetin exerted cytotoxic activities in 786-O and SN12-PM6 cells in a dose- and time-dependent manner. The compound arrested the cell cycle in G0/G1 and G2/M phase with down-regulation of Cyclin D1, CDK4, CDK6, and c-Myc expression. Esculetin also induced apoptosis and the expression of cleaved caspase 3 increased. Additionally, esculetin significantly inhibited 786-O and SN12-PM6 cell migration and invasion, the expression of E-Cadherin increased, and the expression of N-cadherin and vimentin decreased. Taken together, these results suggest that esculetin inhibits proliferation, migration, and invasion of ccRCC and is a potential novel therapeutic agent for the treatment of ccRCC.

Background: Renal cell carcinoma (RCC) is one of the most common types of urological malignant tumors. Despite recent advances in diagnosis and management of RCC, its prognosis remains poor. Emerging evidence has shown that long noncoding RNAs (lncRNAs) play crucial regulatory roles in cancer biology. Materials and methods: The most abundant transcript of long intergenic non-protein coding RNA p53 induced transcript (LINC-PINT) in clear cell RCC (ccRCC) was determined by RT-PCR. Quantitative real-time PCR was performed to examine LINC-PINT expression in paired ccRCC samples and cell lines. The relationship of LINC-PINT expression with clinicopathologic characteristics and clinical outcome was analyzed. The biological function of LINC-PINT was studied by MTS and colony formation. The flow cytometry was used to analyze cell cycle distribution and apoptosis. The subcelluar fractionation and RIP assay was performed to explore the molecular mechanism of LINC-PINT. Western blotting and immunofluorescence was carried out to examine EZH2 and p53. Results: We found that the LINC-PINT was frequently upregulated in ccRCC samples. Furthermore, we observed that the level of LINC-PINT depended on gender as well as on pT and TNM stage of patients with ccRCC. Moreover, patients with high LINC-PINT expression had poor disease-free survival and overall survival. Functionally, overexpression of LINC-PINT promoted ccRCC cell proliferation, induced cell cycle progression, and inhibited apoptosis. LINC-PINT was primarily located in cell nuclei and interacted with EZH2. When EZH2 was knocked down in 769P and OS-RC-2 cells overexpressing LINC-PINT, the effect of LINC-PINT on cell proliferation, cell cycle, and apoptosis was partially reversed. Additionally, inducing p53 by doxorubicin (Dox) promoted LINC-PINT expression. Conclusion: Collectively, our results provide novel insights into the important role of LINC-PINT in ccRCC development and indicate that LINC-PINT may serve as a valuable prognostic biomarker for ccRCC.

Purpose: Smoking is a well-established risk factor for kidney cancer. Analyzing the latest global spatio-temporal trends in the kidney cancer burden attributable to smoking is critical for informing effective public health policies.Methods: Using data from the 2021 GBD database, we examined deaths, disability-adjusted life years (DALYs), and age-standardized rate (ASR) of kidney cancer attributable to smoking across global, regional, and national levels. Trends in ASRs were assessed through estimated annual percentage change (EAPC). We conducted a cross-country analysis to evaluate disparities in the kidney cancer burden from 1990 to 2021, with absolute and relative inequalities measured by the slope index of inequality and concentration index, respectively. Correlation analysis was conducted by the Spearman rank order correlation method. Additionally, we projected age-standardized death and DALYs rates up to 2036 using Bayesian age-period-cohort (BAPC) models in R.Results: Globally, kidney cancer deaths attributable to smoking increased by 67.64%, from 9,673 in 1990 to 16,216 in 2021. Despite this increase, the age-standardized death rate (ASDR) dropped from 0.25 to 0.19 per 100,000 (EAPC: −0.93). Similarly, the age-standardized disability-adjusted life years rate (ASDALY) decreased from 6.17 to 4.37 per 100,000 (EAPC: −1.15). Geographically, areas with a higher Socio-demographic Index (SDI) were the most affected. The positive correlation between higher SDI and increased deaths highlights the role of economic and social factors in disease prevalence. Cross-country analysis shows that while relative inequalities between groups are improving, absolute differences in health burdens continue to grow. Furthermore, projections indicate a gradual decline in ASDR and ASDALY for both sexes from 2022 to 2036.Conclusion: Between 1990 and 2021, both the global ASDR and ASDALY attributable to smoking in kidney cancer, which are positively correlated with SDI, have declined. However, significant demographic and geographic disparities persist, with the disease burden remaining higher in older populations and regions with elevated SDI levels. Moreover, while the overall burden is projected to decline annually over the next 15 years, it is expected to remain significantly higher in men. These findings emphasize the need for region-specific health prevention strategies to reduce smoking-related kidney cancer.

Elevated Gamma-glutamyl transferase (GGT) levels are often suggestive of cholelithiasis, and previous studies have indicated that GGT is highly expressed in the urinary system. Therefore, we hypothesized that there may be an association between GGT levels and calculus of kidney (CK) incidence. To investigate this potential causal relationship, we employed Mendelian randomization (MR) analysis. Additionally, we analyzed the levels of other liver enzymes, including alanine transaminase (ALT) and alkaline phosphatase (ALP). The relationship between GGT levels and CK incidence was analyzed using two-sample Mendelian randomization. Summary Genome-Wide Association Studies data were utilized for this analysis. 33 single nucleotide polymorphisms known to be associated with GGT levels were employed as instrumental variables. We employed several MR methods including IVW (inverse variance weighting), MR-Egger, weighted median, weighted mode, and MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier). Furthermore, we conducted tests for horizontal multivariate validity, heterogeneity, and performed leave-one-out analysis to ensure the stability of the results. Overall, several MR methods yielded statistically significant results with a p-value < 0.05. The results from the IVW analysis yielded an odds ratio (OR) of 1.0062 with a 95% confidence interval (CI) of 1.0016–1.0109 (p = 0.0077). Additional MR methods provided supplementary results: MR-Egger (OR 1.0167, 95% CI 1.0070–1.0266, p = 0.0040); weighted median (OR 1.0058, 95% CI 1.0002–1.0115, p = 0.0423); and weighted mode (OR 1.0083, 95% CI 1.0020–1.0146, p- = 0.0188). Sensitivity analyses did not reveal heterogeneity or outliers. Although potential horizontal pleiotropy emerged, we speculate that this could be attributed to inadequate test efficacy. However, subsequent use of MR-PRESSO did not provide evidence of pleiotropy. Our analysis suggests a positive association between elevated GGT levels and CK incidence, indicating an increased risk of CK development. However, no causal relationship was observed between levels of ALP or ALT and CK incidence.

Background Retroperitoneal infantile hemangioma (RIH), a type of primary retroperitoneal tumors, are exceptionally rare in clinical practice. Infantile hemangiomas typically manifest on the skin’s surface. RIHs are exceptionally rare and typically small. In adults, these tumors often manifest without specific clinical symptoms or detectable signs for a definitive diagnosis. This case report details a patient diagnosed with RIH. We recommend complete excision of the tumor after a comprehensive evaluation, followed by postoperative pathology, to achieve a conclusive diagnosis. We believe that managing critical retroperitoneal structures and vessels intraoperatively presents a significant challenge for all procedures involving primary retroperitoneal tumors. Case summary A 47-year-old male was diagnosed with gallstones and underwent surgery 3 months ago at other institution for unexplained nausea and vomiting. Follow-up imaging 2 months after surgery revealed a retroperitoneal mass below the left renal pole. Upon presentation to our hospital, the patient continued to experience intermittent nausea and vomiting, with no other significant symptoms or signs. Considering the patient’s 8-year history of hypertension, a paraganglioma was initially suspected. We performed the laparoscopic mass resection after a detailed assessment. However, postoperative pathology revealed it a capillary hemangioma (old term)/infantile hemangioma. Conclusion RIHs are exceedingly rare benign tumor. The possibility of malignancy should be ruled out, and surgical resection is recommended following a thorough evaluation, with the diagnosis confirmed through pathological examination.