Background: Neuropilin-1 (NRP-1) is a non-tyrosine kinase receptor interacting with multiple signaling pathways that underpin the biological behavior and fate of cancer cells. However, in pancreatic cancer, the mechanisms underlying the function of NRP-1 in cell proliferation and metastasis and the involvement of regulatory upstream miRNAs remain unclear.Methods: Potential miRNAs were mined by using multiple bioinformatics prediction tools and validated by luciferase assays. The expression of NRP-1 and miRNA-141 (miR-141) in pancreatic tissues and cells was examined by immunohistochemistry, immunoblotting and/or real-time RT-PCR. Stable transfected cells depleted of NRP-1 were generated, and regulatory effects of miR-141 were investigated by transfecting cells with miR-141 mimics and anti-miR-141. Assays of cell viability, proliferation, cell cycle distribution, transwell migration and cell scratch were employed. Xenograft tumor models were established to assess the effects of NRP-1 depletion on tumorigenesis and liver metastasis, and therapeutic effects of miR-141 on tumor growth. The role of miR-141/NRP-1 axis in regulating epithelial–mesenchymal transition (EMT) by co-interacting the TGF-β pathway was examined.Results: In this study, of 12 candidate miRNAs identified, miR-141 showed the strongest ability to regulate NRP-1. In pancreatic cancer tissues and cells, the expression level of NRP-1 was negatively correlated with that of miR-141. NRP-1 was highly expressed in pancreatic cancer tissues compared with normal pancreatic tissues, and its expression levels were positively correlated with tumor grade, lymph metastasis and AJCC staging. NRP-1 depletion inhibited cell proliferation by inducing cell cycle arrest at the G0/G1 phase through upregulating p27 and downregulating cyclin E and cyclin-dependent kinase 2, and reduced cell migration by inhibiting EMT through upregulating E-cadherin and downregulating Snail and N-cadherin. Through downregulating NRP-1, miR-141 mimics showed a similar effect as NRP-1 depletion on cell proliferation and migration. NRP-1 depletion suppressed tumor growth and liver metastasis and miR-141 mimics inhibited the growth of established tumors in mice. NRP-1 depletion and/or miR-141 mimics inhibited the activation of the TGF-β pathway stimulated by TGF-β ligand.Conclusions: The present results indicate that NRP-1 is negatively regulated by miR-141 and the miR-141/NRP-1 axis may serve as potentially valuable biomarkers and therapeutic targets for pancreatic cancer.

Background: Disseminating disease knowledge through concise videos on various platforms is an innovative and efficient approach. However, it remains uncertain whether pancreatic neuroendocrine tumor (pNET)-related videos available on current short video platforms can effectively convey accurate and impactful information to the general public. Objective: Our study aims to extensively analyze the quality of pNET-related videos on TikTok and Bilibili, intending to enhance the development of pNET-related social media content to provide the general public with more comprehensive and suitable avenues for accessing pNET-related information. Methods: A total of 168 qualifying videos pertaining to pNETs were evaluated from the video-sharing platforms Bilibili and TikTok. Initially, the fundamental information conveyed in the videos was documented. Subsequently, we discerned the source and content type of each video. Following that, the Global Quality Scale (GQS) and modified DISCERN (mDISCERN) scale were employed to appraise the educational value and quality of each video. A comparative evaluation was conducted on the videos obtained from these two platforms. Results: The number of pNET-related videos saw a significant increase since 2020, with 9 videos in 2020, 19 videos in 2021, 29 videos in 2022, and 106 videos in 2023. There were no significant improvements in the mean GQS or mDISCERN scores from 2020 to 2023, which were 3.22 and 3.00 in 2020, 3.33 and 2.94 in 2021, 2.83 and 2.79 in 2022, and 2.78 and 2.94 in 2023, respectively. The average quality scores of the videos on Bilibili and Tiktok were comparable, with GQS and mDISCERN scores of 2.98 on Bilibili versus 2.77 on TikTok and 2.82 on Bilibili versus 3.05 on TikTok, respectively. The source and format of the videos remained independent factors affecting the two quality scores. Videos that were uploaded by professionals (hazard ratio=7.02, P=.002) and recorded in specialized popular science formats (hazard ratio=12.45, P<.001) tended to exhibit superior quality. Conclusions: This study demonstrates that the number of short videos on pNETs has increased in recent years, but video quality has not improved significantly. This comprehensive analysis shows that the source and format of videos are independent factors affecting video quality, which provides potential measures for improving the quality of short videos.

Background: Exosomes assume a pivotal role as essential mediators of intercellular communication within tumor microenvironments. Within this context, long noncoding RNAs (LncRNAs) have been observed to be preferentially sorted into exosomes, thus exerting regulatory control over the initiation and progression of cancer through diverse mechanisms. Results: Exosomes were successfully isolated from cholangiocarcinoma (CCA) CTCs organoid and healthy human serum. Notably, the LncRNA titin-antisense RNA1 (TTN-AS1) exhibited a conspicuous up-regulation within CCA CTCs organoid derived exosomes. Furthermore, a significant elevation of TTN-AS1 expression was observed in tumor tissues, as well as in blood and serum exosomes from patients afflicted with CCA. Importantly, this hightened TTN-AS1 expression in serum exosomes of CCA patients manifested a strong correlation with both lymph node metastasis and TNM staging. Remarkably, both CCA CTCs organoid-derived exosomes and CCA cells-derived exosomes featuring pronounced TTN-AS1 expression demonstrated the capability to the proliferation and migratory potential of CCA cells. Validation of these outcomes was conducted in vivo experiments. Conclusions: In conclusion, our study elucidating that CCA CTCs-derived exosomes possess the capacity to bolster the metastasis tendencies of CCA cells by transporting TTN-AS1. These observations underscore the potential of TTN-AS1 within CTCs-derived exosomes to serve as a promising biomarker for the diagnosis and therapeutic management of CCA.

BACKGROUND We explored the relationship of interferon-γ (IFN-γ) and MHC class-I chain related gene A (MICA) genes polymorphisms with hepatocellular carcinoma (HCC) risk, and tried to determine whether the interaction existed between these two genes polymorphisms on the basis of HCC. MATERIAL AND METHODS Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect the genotypes of the 3 single-nucleotide polymorphisms (SNPs) and to analyze the correlation of each SNP with HCC susceptibility in 120 HCC patients and 124 healthy people. The association strength between the 3 SNPs and HCC is represented with odds ratio (OR) and 95% confidence interval (95% CI). Hardy-Weinberg equilibrium (HWE) was tested by χ2 test in the control group. RESULTS GG genotype of IFN-γ rs2069727 polymorphism had apparently different distributions in case and control groups (P<0.05), and might confer increased risk of HCC (OR=3.40, 95%CI=1.23-9.38). Analysis of MICA rs2596542 polymorphism also yielded the same result (OR=2.90, 95%CI=1.10-7.67), as did their risk alleles. Specifically, the interaction between rs2596542 and rs2069705 polymorphisms increased the HCC risk by 1.41 times and between rs2596542 and rs2069727 polymorphisms the increased risk of HCC by 5.56 times. CONCLUSIONS IFN-γ rs2069727 and MICA rs2596542 polymorphisms may be related to the incidence of HCC. Interaction exists between the polymorphisms of IFN-γ and MICA, which may increase risk of HCC.

The aim of the present study was to detect the expression levels of the human telomerase reverse transcriptase (hTERT) gene in hepatocellular carcinoma (HCC), and investigate its significance in the incidence and development of the cancer. HCC tissues and corresponding para-carcinoma liver tissues were surgically collected from 78 patients with HCC who presented to Shandong Provincial Hospital (Jinan, Shandong, China). hTERT expression at the protein and mRNA levels were detected by immunohistochemistry (streptavidin peroxidase method) and reverse transcription polymerase chain reaction, respectively, in the HCC tissues and corresponding para-carcinoma liver tissues of 78 HCC patients and in 12 samples of normal liver tissue. The data were analyzed using SPSS 17.0 statistical software, and employing χ2 tests and t-tests. hTERT protein was mainly expressed in the HCC cell cytoplasm, but was occasionally observed in the cell nucleus. The positive rates of hTERT protein and mRNA expression in the HCC patients were 84.62% (66/78) and 78.21% (61/78), respectively, which was significantly higher compared with the rates of 10.26% (8/78) and 8.97% (7/78) in the paired para-carcinoma liver tissues (P<0.01). hTERT protein and mRNA were not expressed in the normal liver tissues (0/12). χ2 test and t-test analysis revealed that hTERT gene expression was correlated with tumor grade, the presence/absence of a portal vein tumor thrombus, hepatitis B surface antigen positivity and a high α-fetoprotein level (P<0.05) rather than patient age, gender or tumor size. Expression of the hTERT gene may play a pivotal role in the incidence and development of HCC. The hTERT gene potentially serves as an important molecular and biological index for diagnosing and predicating the biological behavior of HCC.

The incidence of non-alcoholic fatty liver (NAFLD) remains high, and many NAFLD patients suffer from severe ischemia-reperfusion injury (IRI). Currently, no practical approach can be used to treat IRI. Puerarin plays a vital role in treating multiple diseases, such as NAFLD, stroke, diabetes, and high blood pressure. However, its role in the IRI of the fatty liver is still unclear. We aimed to explore whether puerarin could protect the fatty liver from IRI. C57BL/6J mice were fed with a high‐fat diet (HFD) followed by ischemia reperfusion injury. We showed that hepatic IRI was more severe in the fatty liver compared with the normal liver, and puerarin could significantly protect the fatty liver against IRI and alleviate oxidative stress. The PI3K-AKT signaling pathway was activated during IRI, while liver steatosis decreased the level of activation. Puerarin significantly protected the fatty liver from IRI by reactivating the PI3K-AKT signaling pathway. However, LY294002, a PI3K-AKT inhibitor, attenuated the protective effect of puerarin. In conclusion, puerarin could significantly protect the fatty liver against IRI by activating the PI3K-AKT signaling pathway.