Methods: The ubiquitination-related gene ubiquitin domain-containing protein 1 (UBTD1) was identified using bioinformatics and single-cell analyses. Subsequently, the ability of UBTD1 to predict CRC prognosis and immune checkpoint correlation was analyzed, the potential drug telatinib targeting UBTD1 was explored, and the correlation between UBTD1 and ferroptosis was analyzed. The role of UBTD1 in CRC and ferroptosis was verified using immunohistochemistry, gene knockout, western blot, cell cloning, and immunofluorescence.

Results: UBTD1 was identified as a significant prognostic and predictive gene for CRC and was involved in regulating immune checkpoint levels and immune cell function of CRC patients with CRC. High UBTD1 expression was found to enhance the presence of immune checkpoints that induce immune escape and inhibit ferroptosis onset. Telatinib may be a potential therapeutic drug targeting UBTD1.

Conclusion: Our study demonstrated that UBTD1 is a prognostic marker for CRC in the regulation of ubiquitination and the tumor immune microenvironment and may serve as a modulator of ferroptosis.]]> https://www.benthamscience.com/article/1464132025-10-06 Background: Recent research has demonstrated the significance of Interferon Gamma- Inducible Protein 30 (IFI30), an interferon gamma-induced protein, in the immune response to cancerous growths. However, the relationship between IFI30 expression levels, patient prognosis, and tumor-infiltrating lymphocytes in clear cell renal cell carcinoma (ccRCC) remains inadequately defined.

Methods: To ascertain the potential link between IFI30 expression, clinical data, and overall survival (OS) in ccRCC patients, we employed diverse databases, which include TCGA, Gene Expression Profiling Interaction Analysis (GEPIA), and UALCAN. Furthermore, an in-depth analysis of the link between tumor-infiltrating immune cells (TIIC) and IFI30 was carried out using the TIMER, GEPIA, and TISIDB databases. Immunohistochemistry (IHC) was utilized to identify the IFI30 and PD-1 expression levels in a tissue microarray. Patents about molecular classification and drugs in ccRCC were reviewed through Worldwide Espacenet®.

Results: The expression of IFI30 demonstrated a strong association with sample type, lymph node stage, tumor grade, and cancer stage. Elevated IFI30 expression was linked to unfavorable Disease- Specific Survival (DSS) and Overall Survival (OS) outcomes (p <0.01). Furthermore, overexpression of IFI30 was strongly linked to immunomodulatory molecules, chemokines, and increased infiltration of regulatory T cells (Tregs), natural killer (NK) CD56 cells, T helper 1 (Th1) cells, cytotoxic T cells, and T helper cells. IHC analysis confirmed a robust correlation between IFI30 and PD-1 expression.

Conclusion: IFI30 is a prognostic biomarker for ccRCC patients. Targeting IFI30 may provide new strategies for cancer therapy and improve the prognosis of ccRCC patients.

Methods: For cellular studies, flow cytometry, colony formation assay, MTT assay, wound healing assay, and ROS measurement were employed. Western blotting was used to assess the expression levels of apoptotic proteins. A subcutaneous tumor xenograft model was established. The analysis included the evaluation of proteins related to the PI3K/AKT signaling pathway, TUNEL, and Ki-67 staining, as well as HE staining.

Results: L-SeMC caused cell death and, in a concentration-dependent manner, reduced the migration, invasion, and proliferation of esophageal cancer cells. Western blot analysis showed that L-SeMC was associated with a decrease in the anti-apoptotic protein Bcl-2 and an increase in the pro-apoptotic protein Bax. It also triggered the mitochondrial apoptosis pathway, promoting the activation of caspase-3 and subsequent cancer cell death induced by L-SeMC. In a dosedependent manner, L-SeMC decreased the phosphorylation of phosphatidylinositol 3-kinase (PI3K) downstream effector molecules. This suggests that L-SeMC inhibits the PI3K/AKT signaling pathway in esophageal cancer cells, contributing to its anticancer effects.

Conclusion: L-SeMC has a strong anticancer effect on human esophageal cancer cells and promotes apoptosis by inhibiting the PI3K/AKT signaling pathway, suggesting that L-SeMC may represent a novel strategy for the treatment of esophageal cancer.

Objective: This study aimed to find an effective resistance-reversed agent of ABC transporter. A series of new β-carboline derivatives have been synthesized and are being applied in various invention patents. One of these is B-9-8, a novel harman dimer, which was synthesized to conduct a series of experiments.

Methods: In this study, we investigated whether B-9-8 could reverse ABCG2-mediated drug resistance by using MTT assay, [3H]-mitoxantrone accumulation/efflux assay, western blot analysis, immunofluorescence analysis, ATPase assay, and molecular modeling assay.

Results: The results showed that B-9-8 could significantly increase the sensitivity to mitoxantrone, SN-38, and topotecan and effectively overcame drug resistance at non-toxic concentrations in ABCG2-overexpressing cells. Further studies showed that B-9-8 increased the intracellular accumulation of [3H]-mitoxantrone by suppressing the efflux function of ABCG2 in ABCG2-overexpressing cells. B-9-8 could down-regulate the ABCG2 protein expression but did not change the subcellular localization of ABCG2. ATPase analysis indicated that B-9-8 inhibited the ATPase activity of ABCG2 in a concentration-dependent manner. In the molecular docking analysis, B-9-8 demonstrated a strong interaction with the human ABCG2 transporter protein.

Conclusion: Our findings indicated that B-9-8 could reverse ABCG2-mediated MDR as a potential and reversible modulator in combination with conventional chemotherapeutic drugs.

Methods: We evaluated the anticancer effect of Morusin in pancreatic cancer cells, including its impact on pancreatic cancer cell proliferation, colony formation potential, migration, invasion, cell cycle and apoptosis. RNA sequencing (RNA-seq) analysis was employed to identify potential genes involved in the anticancer activity of Morusin. Furthermore, RT-qPCR and Western blot analysis were utilized to verify the findings.

Results: Our results demonstrated that Morusin administration significantly impaired cell proliferation, migration and invasive activity of pancreatic cancer cells. Additionally, Morusin induced apoptosis and disrupted cell cycle progression. Importantly, Morusin was found to coregulate SLC6A12, HSPA2, P2RY6 and JPH2 in both cell lines by RNA-seq analysis, with the most significant decrease in mRNA levels of SLC6A12 following administration. Mechanistically, Morusin was found to regulate the expression of SLC6A12 and inhibit NF-κB and β-catenin signaling pathways, which may represent the underlying mechanisms of its antitumor activity.

Conclusion: Our findings suggest that Morusin holds potential as an anti-pancreatic cancer agent by targeting SLC6A12 and modulating its associated signaling pathways.

Methods: This study included NPC patients who experienced RI due to the COVID-19 pandemic. Patient characteristics, details of treatment after RI, compensatory treatment, and survival outcomes were analyzed.

Results: A total of 8 patients were identified, with a median RI duration of 19 days. All patients received an additional fraction of radiotherapy due to the interruption. Following RI, all patients completed the recommended radiotherapy regimen and underwent comprehensive locoregional and systemic assessment three months post-treatment. Complete remission of the nasopharyngeal tumor and cervical lymph nodes was achieved in 7 (87.5%) patients. These patients were administered oral tegafur, gimeracil, and oteracil potassium (S-1) MC. All patients completed one year of MC without experiencing grade 3-4 adverse reactions. With a median follow-up of 34.4 months, no instances of disease recurrence were observed. The 2-year disease-free survival and overall survival were both 100%.

Conclusion: MC may serve as an effective compensatory treatment strategy for NPC patients experiencing RI. These findings offer valuable insights for future clinical trials involving NPC patients with RI due to various reasons.]]> https://www.benthamscience.com/article/1491902025-10-06Introduction: Pancreatic cancer (PC) is a highly aggressive malignancy with limited treatment options and poor prognosis. Dahuang Zhechong Pill, a traditional Chinese medicine, has shown promise in inhibiting inflammation. This study investigates the effects of combining Dahuang Zhechong Pill with TNS4 silencing on PC, focusing on their combined role in suppressing PC progression and exploring potential therapeutic applications. Intellectual property implications related to this combination are also explored.

Methods: Bioinformatic analysis was used to identify the key role of TNS4 in PC. CFPAC-1 PC cells were cultured and genetically modified using lentiviral transfection to stably knock down TNS4 expression. Cell proliferation was assessed using the CCK-8 assay, while cell migration and invasion capabilities were evaluated through Transwell assays. Colony formation and flow cytometry were performed to analyze clonogenic potential and cell cycle distribution, respectively. Apoptosis was assessed using tunel staining. Subcutaneous and orthotopic tumor models were established in nude mice to investigate the in vivo effects. Mice were treated with Dahuang Zhechong Pill by oral gavage. Immunohistochemistry and immunofluorescence were employed to detect the expression of key proteins involved in the NF-κB/VEGF pathway, including E-cadherin and Vimentin. ELISA was used to measure circulating IL-17 and amylase levels in mouse serum to test inflammation response.

Results: TNS4 was upregulated in PC and positively associated with PC progression. TNS4 silencing significantly reduced CFPAC-1 cell proliferation, migration, and invasion in vitro. Flow cytometry demonstrated an increase in G0/G1 phase arrest and apoptosis in the TNS4 silencing group. Subcutaneous models showed the anti-tumor effect of TNS4 silencing. Furthermore, Dahuang Zhechong Pill treatment, when combined with TNS4 knockdown, resulted in a marked decrease in tumor size in orthotopic models. Immunohistochemical analysis revealed reduced expression of NF-κB and VEGF in tumor tissues from the combination treatment group. ELISA results indicated lower levels of serum IL-17, and amylase and higher levels of insulin in combination-treated mice.

Discussion: We proposed an innovative therapeutic patent combining traditional Chinese medicine with targeted gene silencing to inhibit PC progression. By investigating the synergistic effects of TNS4 silencing and Dahuang Zhechong Pill in suppressing the NF-κB/VEGF signaling pathway, our findings highlighted a promising strategy that targets tumor proliferation and modulates the inflammatory microenvironment in PC.

Conclusion: Dahuang Zhechong Pill, in combination with TNS4 silencing, effectively inhibits the NF-κB/VEGF pathway and inflammation response, leading to reduced PC progression. These findings suggest a potential therapeutic approach for targeting PC through the combined use of traditional Chinese medicine and gene editing.