Diverse roles of UBE2T in cancer (Review).

As a leading cause of mortalities worldwide, cancer results from accumulation of both genetic and epigenetic alterations. Disruption of epigenetic regulation in cancer, particularly aberrant ubiquitination, has drawn increasing interest in recent years. The present study aimed to review the roles of ubiquitin­conjugating enzyme E2 T (UBE2T) and its associated pathways in the pathogenesis of pan­cancer, and the development of small­molecule modulators to regulate ubiquitination for treatment strategies. The current study comprehensively investigated the expression landscape and functional significance of UBE2T, as well as its correlation with cancer cell sensitivity to chemotherapy/radiotherapy. Multiple levels of evidence suggested that aberrant UBE2T played important roles in pan­cancer. Information was collected from 16 clinical trials on ubiquitin enzymes, and it was found that these molecules had an important role in the ubiquitin­proteasome system. Further studies are necessary to explore their feasibility and effectiveness as diagnostic and prognostic biomarkers, or as up/down­stream and therapeutic targets for cancer treatment.

Association between SII and hepatic steatosis and liver fibrosis: A population-based study.

Background: The systemic immune-inflammation index (SII) is a novel marker of inflammation, and hepatic steatosis and fibrosis are associated with inflammation. This study aimed to investigate the possible relationship between SII and hepatic steatosis and fibrosis. Methods: The datasets from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 were used in a cross-sectional investigation. Multivariate linear regression models were used to examine the linear connection between SII and controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Fitted smoothing curves and threshold effect analysis were used to describe the nonlinear relationship. Results: This population-based study included a total of 6,792 adults aged 18-80 years. In a multivariate linear regression analysis, a significant positive association between SII and CAP was shown [0.006 (0.001, 0.010)]. This positive association in a subgroup analysis was maintained in men [0.011 (0.004, 0.018)] but not in women. Furthermore, the association between SII and CAP was nonlinear; using a two-segment linear regression model, we found an inverted U-shaped relationship between SII and CAP with an inflection point of 687.059 (1,000 cells/µl). The results of the multiple regression analysis showed that the relationship between SII and LSM was not significant (P = 0.263). Conclusions: Our findings imply that increased SII levels are linked to hepatic steatosis, but SII is not linked to liver fibrosis. To confirm our findings, more large-scale prospective investigations are needed.

[Clinical value of activin A in early identification of moderate and severe acute pancreatitis: a prospective study].

OBJECTIVE: To explore the value of serum activin A (ACT-A) level in early identification of moderate and severe acute pancreatitis (AP). METHODS: A prospective case control study was conducted. A total of 120 patients with AP admitted to department of hepatobiliary surgery of Affiliated Nanhua Hospital of Hengyang Medical College of University of South China between October 2020 and April 2022 were recruited. According to the revised Atlanta classification, all patients were classified into mild AP group and moderate-to-severe AP group. The blood samples within 24 hours of onset were drawn, and the serum ACT-A and C-reactive protein (CRP) levels were detected by enzyme-linked immunosorbent assay (ELISA). The Ranson score and the modified CT severity index (MCTSI) were performed. Pearson correlation method was used to analyze the correlation of various parameters. The receiver operator characteristic curve (ROC curve) was plotted to analyze the predictive value of ACT-A and CRP for moderate-to-severe AP. RESULTS: A total of 120 patients with AP were enrolled, including 83 patients with mild AP and 37 patients with moderate-to-severe AP. Serum ACT-A and CRP levels within 24 hours of onset in the moderate-to-severe AP group were significantly higher than those in the mild AP group [ACT-A (ng/L): 140.4±37.7 vs. 53.9±30.5, lg CRP: 1.42±0.91 vs. 0.77±0.70, both P < 0.01], and the Ranson score and MCTSI score were also significantly higher than those in the mild AP group (Ranson score: 5.3±1.3 vs. 1.8±1.6, MCTSI score: 5.5±1.0 vs. 2.7±1.2, both P < 0.01). Correlation analysis showed that the serum ACT-A level was positively correlated with serum CRP level, Ranson score and MCTSI score (R2 value was 0.272, 0.841, 0.616, respectively, all P < 0.05). ROC curve analysis showed that the serum ACT-A, CRP and Ranson score had predictive value for moderate-to-severe AP. The area under the ROC curve (AUC) was 0.948 [95% confidence interval (95%CI) was 0.909-0.986], 0.711 (95%CI was 0.606-0.815), 0.946 (95%CI was 0.910-0.982), respectively. When serum ACT-A > 112.6 ng/L, the sensitivity and specificity of predicting moderate-to-severe AP were 78.38% and 96.39%, respectively, which was better than serum CRP with sensitivity and specificity of 72.92% and 66.27%, respectively, and the specificity was better than Ranson score (71.08%). CONCLUSIONS: ACT-A can be detected in the early stage of AP, and it is positively correlated with the disease severity, which can early identify moderate-to-severe AP.

Saturation Effect of Body Mass Index on Bone Mineral Density in Adolescents of Different Ages: A Population-Based Study.

Background: Adolescence is a critical period for bone development, and peak bone mass may be reached in late adolescence. Boosting bone accumulation at this time can help preserve adult bone health and avoid osteoporosis later in life. Body mass index (BMI) has been found to have a favorable impact on bone mineral density (BMD) in previous research. However, excessive obesity is harmful to health and may lead to various systemic diseases. Therefore, finding an appropriate BMI to maintain a balance between obesity and BMD is critical for adolescents. Methods: The datasets from the National Health and Nutrition Examination Survey (NHANES) 2011-2020 were used in a cross-sectional investigation. Multivariate linear regression models were used to examine the linear connection between BMI and BMD. Fitted smoothing curves and threshold effect analysis were used to describe the nonlinear relationship. Subgroup analyses were then conducted based on gender and age. Results: This population-based study included a total of 6,143 adolescents aged 8-19 years. In a multivariate linear regression analysis, a good association between BMI and total BMD was shown [0.014 (0.013, 0.014)]. This positive association was maintained in all subgroup analyses grouped by sex and age. Furthermore, the association between BMI and BMD was nonlinear with a saturation point present, as evidenced by smoothed curve fitting. According to the threshold effect study, with an age group of two years, adolescents of different ages had different BMI saturation values with respect to BMD. Conclusions: Our study showed a significant positive and saturated association between BMI and BMD in adolescents aged 8-19 years. Maintaining BMI at saturation values may reduce other adverse effects while achieving optimal BMD.

Arginine methyltransferase inhibitor 1 exhibits antitumor effects against cervical cancer in vitro and in vivo.

Protein arginine methyltransferase 5 (PRMT5), a type II PRMT, is highly expressed in several types of tumors including cervical cancer. Arginine methyltransferase inhibitor 1 (AMI-1) inhibits solid tumors by targeting PRMT5. However, the effect of AMI-1 on cervical cancer is still unknown. In this study, we provided the first evidence that AMI-1 reduced cervical cancer cell proliferation, colony formation and promoted cell apoptosis in vitro. Suppression of tumorigenicity was also confirmed in vivo. Mechanistic studies revealed that AMI-1 significantly reduced PRMT5 level in cells and mice xenografts model of cervical cancer. These results suggest that AMI-1 inhibits cervical cancer by type II PRMT5.

Arginine methyltransferase inhibitor 1 inhibits gastric cancer by downregulating eIF4E and targeting PRMT5.

Arginine methylation is carried out by protein arginine methyltransferase (PRMTs) family. Arginine methyltransferase inhibitor 1 (AMI-1) is mainly used to inhibit type I PRMT activity in vitro. However, the effects of AMI-1 on type II PRMT5 activity and gastric cancer (GC) remain unclear. In this study, we provided the first evidence that AMI-1 significantly inhibited GC cell proliferation and migration while induced GC cell apoptosis, and reduced the expression of PRMT5, eukaryotic translation initiation factor 4E (eIF4E), symmetric dimethylation of histone 3 (H3R8me2s) and histone 4 (H4R3me2s). In addition, AMI-1 inhibited tumor growth, downregulated eIF4E, H4R3me2s and H3R8me2s expression in mice xenografts model of GC. Collectively, our results suggest that AMI-1 inhibits GC by downregulating eIF4E and targeting type II PRMT5.