ZNF488 Promotes the Invasion and Migration of Pancreatic Carcinoma Cells through the Akt/mTOR Pathway.

OBJECTIVE: Studies have demonstrated that zinc finger protein 488 (ZNF488) is highly expressed in pancreatic carcinoma (PC), but its effect on PC and its molecular mechanism remains unclear. METHODS: Real-time fluorescent quantitative PCR (RT-qPCR) was employed to detect the ZNF488 expression in PC patients' cancer tissues and cell lines. After interfering with or overexpressing ZNF488 in PANC-1 and AsPC-1 cells, respectively, the CCK-8, cell cloning, Transwell, and scratch assays were performed to detect cell proliferation, cell viability, invasion ability, and migration ability. In addition, Western blot was applied to assess the protein expression of Akt, p-Akt, mTOR, and p-mTOR in the Akt-mTOR pathway. RESULTS: The ZNF488 expression was evidently raised in PC tissues and cell lines, and the starBase V3.0 database indicated that the higher the ZNF488 expression, the lower the survival rate of PC patients. Furthermore, we discovered that overexpressing ZNF488 can markedly promote the proliferation, invasion, and migration of PC cells. At the same time, highly expressed ZNF488 distinctly increased the p-Akt and p-mTOR expressions and the p-Akt/Akt and p-mTOR/mTOR ratios. However, after knocking down the ZNF488 expression, it had the opposite results. In addition, the Akt agonist SC79 can alleviate the effect of ZNF488 knockdown on Akt/mTOR pathway-related proteins, while Akt inhibitor AZD5363 had the opposite effect. CONCLUSION: ZNF488 could promote the proliferation, invasion, and migration of PC cells, and its mechanism may be related to the activation of the Akt/mTOR pathway. This study demonstrated that ZNF488 could be used as a molecular target for diagnosing and treating PC.

Silver Nanoparticles Improve the Biocompatibility and Reduce the Immunogenicity of Xenogeneic Scaffolds Derived from Decellularized Pancreas.

Xenogeneic scaffolds derived from the decellularized pancreas are plausible biomedical materials for pancreatic tissue engineering applications. During the decellularized process, the ultrastructure of extracellular matrices, including collagen fibers, was destructed, which leads to the decrease of mechanical strength and the immune-inflammatory response after transplantation in vivo. The cross-linking method plays an important role in increasing mechanical strength and reducing the inflammatory potential of decellularized scaffolds. However, no ideal cross-linking agent has been identified for decellularized pancreatic scaffolds yet. In this study, a cyclic perfusion system was used to cross-link decellularized pancreatic scaffolds from Sprague Dawley rat with silver nanoparticles (AgNPs). The optimum concentration of AgNPs was selected according to the scanning electron microscope observation and mechanical evaluation, as well as cytotoxicity to human umbilical vein endothelial cells and MIN-6 cell lines in vitro. The inflammation after transplantation in vivo was evaluated by hematoxylin and eosin staining; M1/M2 polarization phenotype of macrophages was further evaluated. Our results showed that after cross-linking, the scaffold possessed better mechanical property and biocompatibility, with the polarization of M2 macrophages increased. Thus, AgNP-cross-linked pancreatic acellular scaffold can provide an ideal scaffold source for pancreatic tissue engineering.

Comparisons of short-term and long-term results between laparoscopic between open pancreaticoduodenectomy for pancreatic tumors: A systematic review and meta-analysis.

Objective: The efficacy of pancreaticoduodenectomy and open pancreaticoduodenectomy for pancreatic tumors is controversial. The study aims to compare the efficacy of laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) in the treatment of pancreatic tumors through systematic evaluation and meta-analysis. Methods: PubMed, Embase, Cochrane Library and Web of science databases were searched for clinical studies on the treatment of pancreatic tumors with LPD and OPD. The end time for the searches was 20 July 2022. Rigorous inclusion and exclusion criteria were used to screen the articles, the Cochrane manual was used to evaluate the quality of the included articles, and the stata15.0 software was used for statistical analysis of the indicators. Results: In total, 16 articles were included, including two randomized controlled trials and 14 retrospective studies. Involving a total of 4416 patients, 1275 patients were included in the LPD group and 3141 patients in the OPD group. The results of the meta-analysis showed that: the operation time of LPD was longer than that of OPD [WMD = 56.14,95% CI (38.39,73.89), p = 0.001]; the amount of intraoperative blood loss of LPD was less than that of OPD [WMD = -120.82,95% CI (-169.33, -72.30), p = 0.001]. No significant difference was observed between LPD and OPD regarding hospitalization time [WMD = -0.5,95% CI (-1.35, 0.35), p = 0.250]. No significant difference was observed regarding postoperative complications [RR = 0.96,95% CI (0.86,1.07, p = 0.463]. And there was no significant difference regarding 1-year OS and 3-year OS: 1-year OS [RR = 1.02,95% CI (0.97,1.08), p = 0.417], 3-year OS [RR = 1.10 95% CI (0.75, 1.62), p = 0.614%]. Conclusion: In comparison with OPD, LPD leads to less blood loss but longer operation time, therefore the bleeding rate per unit time of LPD is less than that of OPD. LPD has obvious advantages. With the increase of clinical application of LPD, the usage of LPD in patients with pancreatic cancer has very good prospect. Due to the limitations of this paper, in future studies, more attention should be paid to high-quality, multi-center, randomized controlled studies.

Analysis of the Effect of Robots in the Treatment of Pancreatic Cancer Based on Smart Medicine.

In order to study the effect of robots in the treatment of pancreatic cancer in the context of smart medical, this paper improves the robot recognition technology and data processing technology and improves the system kernel algorithm through the hash algorithm. Unlike the traditional sequencing method that directly uses the gray average value as a feature, the hash algorithm calculates the gray three-average value of each frame block and uses the difference of the three-average value of adjacent frame blocks to perform detection. Moreover, this paper proposes a detection and localization scheme based on hash local matching, which consists of two parts: coarse matching and fine matching. In addition, this paper designs a control experiment to analyze the effect of robots in the treatment of pancreatic cancer, counts multiple sets of data, and uses mathematical statistics to process and visually display the experimental data. The research shows that the robot has a good clinical effect in the treatment of pancreatic cancer.

LncRNA TP73-AS1 enhances the malignant properties of pancreatic ductal adenocarcinoma by increasing MMP14 expression through miRNA -200a sponging.

Pancreatic ductal adenocarcinoma (PDAC) is an invasive and aggressive cancer that remains a major threat to human health across the globe. Despite advances in cancer treatments and diagnosis, the prognosis of PDAC patients remains poor. New and more effective PDAC therapies are therefore urgently required. In this study, we identified a novel host factor, namely the LncRNA TP73-AS1, as overexpressed in PDAC tissues compared to adjacent healthy tissue samples. The overexpression of TP-73-AS1 was found to correlate with both PDAC stage and lymph node metastasis. To reveal its role in PDCA, we targeted TP73-AS1 using LnRNA inhibitors in a range of pancreatic cancer (PC) cell lines. We found that the inhibition of TP73-AS1 led to a loss of MMP14 expression in PC cells and significantly inhibited their migratory and invasive capacity. No effects of TP73-AS1 on cell survival or proliferation were observed. Mechanistically, we found that TP73-AS1 suppressed the expression of the known oncogenic miR-200a. Taken together, these data highlight the prognostic potential of TP73-AS1 for PC patients and highlight it as a potential anti-PDAC therapeutic target.

Pancreatic extracellular matrix and platelet-rich plasma constructing injectable hydrogel for pancreas tissue engineering.

The development of pancreatic extracellular matrices enriched with insulin-secreting ß-cells is a promising tissue engineering approach to treat type 1 diabetes. However, its long-term therapeutic efficacy is restricted by the defensive mechanism of host immune response and the lack of developed vascularization as appropriate after transplantation. Platelet-rich plasma (PRP), as an autologous platelet concentrate, contains a large number of active factors that are essential for the cell viability, vascularization, and immune regulation. In this study, we have incorporated pancreatic extracellular matrix (PEM) with PRP to develop a three-dimensional (3D) injectable PEM-PRP hydrogel to coculture and transplant rat insulinoma cells (INS-1) and human umbilical vein endothelial cells (HUVECs). Results from this study demonstrated that PEM-PRP hydrogel mimicked the biochemical compositions of native extracellular matrices, and possessed the enhanced elastic modulus and resistance to enzymatic degradation that enabled biomaterials to maintain its volume and slowly degrade. Additionally, PEM-PRP hydrogel could release growth factors in a sustained manner. In vitro, PEM-PRP hydrogel significantly promoted the viability, insulin-secreting function, and insulin gene expression of gel encapsulated INS-1 cells. Moreover, HUVECs encapsulated in PEM-PRP hydrogel were found to constitute many lumen-like structures and exhibited high expression of proangiogenic genes. In vivo transplantation of PEM-PRP hydrogel encapsulated with INS-1 cells and HUVECs improved the viability of INS-1 cells, promoted vascularization, inhibited the host inflammatory response, and reversed hyperglycemia of diabetic rats. Our study suggests that the PEM-PRP hydrogel offers excellent biocompatibility and proangiogenic property, and may serve as an effective biomaterial platform to maintain the long-term survival and function of insulin-secreting ß cells.

Enhanced vascularization and biocompatibility of rat pancreatic decellularized scaffolds loaded with platelet-rich plasma.

The ultimate goal of pancreatic tissue engineering is to create a long-lived substitute organ to treat diabetes. However, the lack of neovascularization and the occurrence of immune response limit the efficacy of tissue-engineered pancreas after in vivo transplantation. Platelet-rich plasma (PRP) is an autologous platelet concentrate containing a large number of growth factors and immunoregulatory factors. The aim of this study was to evaluate rat pancreatic decellularized scaffold (PDS) loaded with PRP for vascularization, host inflammatory response and macrophage polarization in an animal model. The study results indicated that compared to PDS, PRP-loading PDS exhibited the enhanced mechanical properties and released growth factors in a slow and sustained manner to supplement the loss of growth factors during decellularization. In vitro, human umbilical vein endothelial cells (HUVECs) were seeded in PDS and PRP-loading PDS, and cultured in the circular perfusion system. When compared with PDS, PRP-loading PDS significantly promoted the colonization, proliferation and pro-angiogenic genes expression of cells on scaffolds. In vivo, PDS loaded with PRP then re-endothelialized with HUVECs were implanted subcutaneously in rats, which enhanced the angiogenesis of scaffolds, inhibited the host inflammatory response, and induced the polarization dominated by pro-regenerative M2 macrophages that also facilitated tissue vascular regeneration. Thus, the re-endothelialized PRP-loading PDS may represent a promising bioengineered pancreas with sustained vascularization and excellent biocompatibility.