The role of histone H1.2 in pancreatic cancer metastasis and chemoresistance.

AIMS: Pancreatic cancer (PC) is a highly metastatic malignant tumor of the digestive system. Drug resistance frequently occurs during cancer treatment process. This study aimed to explore the link between chemoresistance and tumor metastasis in PC and its possible molecular and cellular mechanisms. METHODS: A Metastasis and Chemoresistance Signature (MCS) scoring system was built and validated based on metastasis- and chemoresistance-related genes using gene expression data of PC, and the model was applied to single-cell RNA sequencing data. The influence of linker histone H1.2 (H1-2) on PC was explored through in vitro and in vivo experiments including proliferation, invasion, migration, drug sensitivity, rescue experiments and immunohistochemistry, emphasizing its regulation with c-MYC signaling pathway. RESULTS: A novel MCS scoring system accurately predicted PC patient survival and was linked to chemoresistance and epithelial-mesenchymal transition (EMT) in PC single-cell RNA sequencing data. H1-2 emerged as a significant prognostic factor, with its high expression indicating increased chemoresistance and EMT. This upregulation was mediated by c-MYC, which was also found to be highly expressed in PC tissues. CONCLUSION: The MCS scoring system offers insights into PC chemoresistance and metastasis potential. Targeting H1-2 could enhance therapeutic strategies and improve PC patient outcomes.

Identifying suitable candidates for pancreaticoduodenectomy with extended lymphadenectomy for pancreatic ductal adenocarcinoma.

BACKGROUND: To evaluate long-term quality of life and survival in pancreatic ductal adenocarcinoma (PDAC) patients after pancreatoduodenectomy with extended lymphadenectomy (PDEL) and identify candidates. METHODS: Patients with resectable PDAC with ≥1 examined lymph node (LN) during pancreatoduodenectomy (PD), and were divided into the PD with standard lymphadenectomy (PDSL) and PDEL groups. Perioperative data, long-term quality of life and survival were compared, and the prognostic effect of LNs ± in every peripancreatic station were analysed. RESULTS: Screening 446 PDAC patients, 237 and 126 were included in the PDSL and PDEL groups, respectively. The PDEL group showed a longer operation time, greater intraoperative blood loss, severe diarrhoea, a higher incidence of grade III complications. Notably, the PDEL patients experienced significant relief from low back pain and diarrhoea, with an obvious survival advantage (p = 0.037), especially in patients with preoperative tumor contact with vascular and pathological N0; however, LNs+ in any station (No. 8p, 12, 14, or 16) were associated with a poorer prognosis. The vascular reconstruction, T and N stage were independent risk factors for survival. CONCLUSION: PDEL can relieve symptoms and prolong the survival of PDAC patients with acceptable complications, and EL should be performed regardless of preoperative LN enlargement.

Increased PRIM2 expression associated with poor-prognosis in patients with pancreatic ductal adenocarcinoma.

OBJECTIVES: To explore the association between PRIM2 expression and prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) from multi clinic centers. METHODS: Samples from PDAC patients were collected and processed to tissue microarray (TMA). PRIM2 expression was detected by immunohistochemistry (IHC) of in 127 enrolled PDAC patients, which underwent surgical resection from January 2012 to December 2018, with complete follow-up, were enrolled and grouped by PRIM2 stain level into two groups. The expression differences, the association to clinicopathologic features and the survival were evaluated by the groups. Data of RNA/protein expression and clinical features from public databases were used for validation. RESULTS: PRIM2 was highly expressed in PDAC patients and associated with poor-prognosis in patients with PDAC. Association was found between increased PRIM2 levels and pathology grade (p = 0.050). Moreover, in multivariate analysis of survival, the highly expression of PRIM2 was identified as an independent risk factor for poor survival (HR1.78, p = 0.031). Analysis on public databases validated above results. CONCLUSIONS: High expression of PRIM2 associated with poor prognosis in PDAC patients, PRIM2 could be used as an independent risk indicator.

Bridging cultures: Chinese elements in scientific illustrations.

In the context of globalization, the integration of cultural elements into scientific research, particularly through the incorporation of traditional Chinese cultural motifs in scientific illustrations, represents a novel frontier in enhancing the universality and appeal of scientific discoveries. This paper explores the innovative practice of embedding traditional Chinese cultural elements into scientific paper illustrations, highlighting its significant role in augmenting the global appeal of research findings, promoting diversity and innovation in scientific inquiry, and facilitating cross-cultural understanding. Through a series of case studies, including symbolic representations of ancient myths and the use of traditional themes to elucidate complex scientific phenomena, we demonstrate how this cultural integration not only makes scientific content more accessible and engaging but also fosters a deeper appreciation of Chinese heritage among international audiences. This approach not only bridges the gap between science and culture but also contributes to a more inclusive and interconnected global scientific community, underscoring the importance of cultural diversity in enriching scientific exploration and communication.

CircPTPRA promotes the progression of pancreatic ductal adenocarcinoma via the miR-140-5p/LMNB1 axis.

BACKGROUND: Growing evidences suggest that circular RNAs (circRNAs) are important factors in cancer progression. Nevertheless, the role of circRNAs in the progression of pancreatic ductal adenocarcinoma (PDAC) remains unclear. METHODS: CircPTPRA was identified based on our previous circRNA array data analysis. Wound healing, transwell, and EdU assays were performed to investigate the effect of circPTPRA on the migration, invasion, and proliferation of PDAC cells in vitro. RNA pull-down, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), and dual-luciferase reporter assays were conducted to verify the binding of circPTPRA with miR-140-5p. Subcutaneous xenograft model was constructed for in vivo experiment. RESULTS: CircPTPRA was significantly upregulated in PDAC tissues and cells compared to normal controls. Moreover, circPTPRA overexpression was positively correlated with lymph node invasion and worse prognosis in PDAC patients. In addition, overexpression of circPTPRA promoted PDAC migration, invasion, proliferation, and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, circPTPRA upregulates LaminB1 (LMNB1) expression by sponging miR-140-5p and ultimately promotes the progression of PDAC. CONCLUSIONS: This study revealed that circPTPRA plays an important role in the progression of PDAC by sponging miR-140-5p. It can be explored as a potential prognostic marker and therapeutic target for PDAC.

Comparison of the biological and functional characteristics of mesenchymal stem cells from intrahepatic and identical bone marrow.

In our privious work, our reseach group characterized a population of hepatic-sourced mesenchymal stem cells (MSCs) called MLpvNG2+ cells. In the present study, we compared the biological and functional characteristics of naïve MLpvNG2 cells with identical bone marrow-derived MSCs (niBM-MSCs) using in vitro (conditioned media) and in vivo (a well-set diethylnitrosamine (DEN)-induced liver fibrotic/cirrhotic murine model) procedures. The intrahepatic-sourced mesodermal MLpvNG2+ cells exhibited some biological characteristics (e.g., a set of surface markers) similar to those of extrahepatic niBM-MSCs. In responsed to signals of pathological conditions, such as singals of fibrotic/cirrhotic liver, MLpvNG2+ cells showed higher survival and favored differentiation into ALB(+) and G6Pc(+) hepatocytes, whereas niBM-MSCs predominantly differentiated into CK/KRT19(+) cholangiocytes. We identified C/EBPα/ß expression as a biological characteristic differentiating these two populations of MSCs, wherein MLpvNG2+ cells are likely regulated by C/EBPß transcriptional signaling, whereas niBM-MSCs are likely controlled by C/EBPα transcriptional signaling. Notably, although C/EBPα and C/EBPß transcriptional signaling regulate hepatocyte and cholangiocyte fate, respectively, the expression of these proteins in MLpvNG2+ cells is, to our knowledge, reported for the first time in the present study. We used anti-C/EBP neutralizing antibodies (Abs) both in vitro and in vivo to determine the functional characteristics of these proteins. We conclude that the biological characteristics of these two populations of MSCs depend on their differential C/EBPα/ß expression patterns.

Decellularized Liver Scaffold for Liver Regeneration.

After being initially hailed as the ultimate solution to end-stage organ failure, such as end-stage liver disease (ESLD), engineering of vascularized tissues has stalled because of the need for a well-structured circulatory system that can maintain the cells to be seeded inside the construct.In the field of regenerative medicine, decellularized scaffolds, derived mainly from various non-autologous whole organs, have become an emerging treatment technique to overcome this obstacle. As a result of significant progress made in recent years, organogenesis through whole-organ decellularization scaffolds may now become more feasible than ever before. In this chapter, we describe in detail the necessary steps for liver organogenesis using a decellularized acellular scaffold (DAS), seed cell isolation, and recellularization in a bioreactor-like culture system. This new technique to re-engineer organs may have major implications for the fields of drug discovery, organ transplantation, and ultimately regenerative medicine.

A novel bioscaffold with naturally-occurring extracellular matrix promotes hepatocyte survival and vessel patency in mouse models of heterologous transplantation.

BACKGROUND: Naïve decellularized liver scaffold (nDLS)-based tissue engineering has been impaired by the lack of a suitable extracellular matrix (ECM) to provide "active micro-environmental" support. AIM: The present study aimed to examine whether a novel, regenerative DLS (rDLS) with an active ECM improves primary hepatocyte survival and prevents thrombosis. METHODS: rDLS was obtained from a 30-55% partial hepatectomy that was maintained in vivo for 3-5 days and then perfused with detergent in vitro. Compared to nDLS generated from normal livers, rDLS possesses bioactive molecules due to the regenerative period in vivo. Primary mouse hepatocyte survival was evaluated by staining for Ki-67 and Trypan blue exclusion. Thrombosis was assessed by immunohistochemistry and ex vivo diluted whole-blood perfusion. Hemocompatibility was determined by near-infrared laser-Doppler flowmetry and heterotopic transplantation. RESULTS: After recellularization, rDLS contained more Ki-67-positive primary hepatocytes than nDLS. rDLS had a higher oxygen saturation and blood flow velocity and a lower expression of integrin αIIb and α4 than nDLS. Tumor necrosis factor-α, hepatocyte growth factor, interleukin-10, interleukin-6 and interleukin-1ß were highly expressed throughout the rDLS, whereas expression of collagen-I, collagen-IV and thrombopoietin were lower in rDLS than in nDLS. Improved blood vessel patency was observed in rDLS both in vitro and in vivo. The results in mice were confirmed in large animals (pigs). CONCLUSION: rDLS is an effective DLS with an "active microenvironment" that supports primary hepatocyte survival and promotes blood vessel patency. This is the first study to demonstrate a rDLS with a blood microvessel network that promotes hepatocyte survival and resists thrombosis.

Correction: Introgression of opaque2 into Waxy Maize Causes Extensive Biochemical and Proteomic Changes in Endosperm.

[This corrects the article DOI: 10.1371/journal.pone.0158971.].

Introgression of opaque2 into Waxy Maize Causes Extensive Biochemical and Proteomic Changes in Endosperm.

Waxy maize is prevalently grown in China and other countries due to the excellent characters and economic value. However, its low content of lysine can't meet the nutritional requirements of humans and livestock. In the present study, we introgressed the opaque2 (o2) allele into waxy maize line Zhao OP-6/O2O2 by using marker-assisted selection (MAS) technique and successfully improved the lysine content and quality of waxy maize. Transcript abundance analysis indicated that the wx1 expression levels had no difference between Zhao OP-6/o2o2 and Zhao OP-6/O2O2. However, Zhao OP-6/o2o2 was characterized by a phenotype of hard and vitreous kernels and accumulation of protein bodies at smaller size (one third of that of parents) but in larger numbers. Biochemical analyses showed that Zhao OP-6/o2o2 had 16.7% less free amino acids than Zhao OP-6/O2O2, especially those derived from glycolytic intermediates, but its content of lysine was increased by 51.6% (0.47% vs. 0.31%). The content of amylopectin was 98.5% in Zhao OP-6/o2o2, significantly higher than that in Zhao OP-6/O2O2 (97.7%). Proteomic analyses indicated that o2 introgression not only decreased the accumulation of various zein proteins except for 27-kDa γ-zein, but also affected other endosperm proteins related to amino acid biosynthesis, starch-protein balance, stress response and signal transduction. This study gives us an intriguing insight into the metabolism changes in endosperm of waxy maize introgressed with opaque2.