DHX38 restricts chemoresistance by regulating the alternative pre-mRNA splicing of RELL2 in pancreatic ductal adenocarcinoma.

Intron retention plays an important role in cancer progression and chemotherapy resistance and seems to be essential for the maintenance of genome stability in cancer. Here, our goal was to analyze the role of receptor expressed in lymphoid tissue (Relt)-like 2 (RELL2) intron 4 retention in promoting pancreatic ductal adenocarcinoma (PDAC) progression. Our results showed that intron retention (IR) occurs at the fourth intron of RELL2 transcript in gemcitabine resistant PDAC cells, however, the regulatory mechanism and the clinical implications of IR of RELL2 are unclear. Firstly, we found that RELL2 plays an anti-oncogenic role in PDAC by performing in vitro functional assays including cell proliferation, GEM cytotoxicity assay and apoptosis. Subsequently, we identified the upstream gene of RELL2, DEAH-Box Helicase 38 (DHX38), and demonstrated the direct interaction between DHX38 and RELL2 by RIP-qPCR. We also found that altered expression of DHX38 resulted in corresponding changes in intron 4 retention of RELL2. Importantly, we unveiled that overexpression of DHX38 on the basis of knocking down of the fourth intron of RELL2 resulted in an impaired intron 4 intention. Overall, our study identified a new IR site in PDAC, which could be a possible target for PDAC therapy.

Venous resection increases risk of chyle leak after total pancreatectomy for pancreatic tumors.

BACKGROUND: Existing research on chyle leak (CL) after pancreatic surgery is mostly focused on pancreaticoduodenectomy and lacks investigation on total pancreatectomy (TP). This study aimed to explore potential risk factors of CL and develop a predictive model for patients with pancreatic tumor undergoing TP. METHODS: This retrospective study enrolled 90 consecutive patients undergoing TP from January 2015 to December 2023 at Peking Union Medical College Hospital. According to the inclusion criteria, 79 patients were finally included in the following analysis. The LASSO regression and multivariate logistic regression analysis were performed to identify risk factors associated with CL and construct a predictive nomogram. Then, the ROC analysis, calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were performed to assess its discrimination, accuracy, and efficacy. Due to the small sample size, we adopted the bootstrap resampling method with 500 repetitions for validation. Lastly, we plotted and analyzed the trend of postoperative drainage volume in CL patients. RESULTS: We revealed that venous resection (OR = 4.352, 95%CI 1.404-14.04, P = 0.011) was an independent risk factor for CL after TP. Prolonged operation time (OR = 1.473, 95%CI 1.015-2.237, P = 0.052) was also associated with an increased incidence of CL. We included these two factors in our prediction model. The area under the curve (AUC) was 0.752 (95%CI 0.622-0.874) after bootstrap. The calibration curve, DCA and CIC showed great accuracy and clinical benefit of our nomogram. In patients with CL, the mean drainage volume was significantly higher in venous resection group and grade B CL group. CONCLUSION: Venous resection was an independent risk factor for chyle leak after TP. Patients undergoing vascular resection during TP should be alert for the occurrence of CL after surgery. We then constructed a nomogram consisted of venous resection and operation time to predict the odds of CL in patients undergoing TP.

EGR1 induces EMT in pancreatic cancer via a P300/SNAI2 pathway.

BACKGROUND: The prognosis of pancreatic cancer patients remains relatively poor. Although some patients would receive surgical resection, distant metastasis frequently occurs within one year. Epithelial-mesenchymal transition (EMT), as a pathological mechanism in cancer progression, contributed to the local and distant metastasis of pancreatic cancer. METHODS: Tissue microarray analysis and immunohistochemistry assays were used to compare the expression of EGR1 in pancreatic cancer and normal pancreatic tissues. Transwell chambers were used to evaluated the migration and invasion ability of cancer cells. Immunofluorescence was utilized to assess the expression of E-cadherin. ChIP-qPCR assay was applied to verify the combination of EGR1 and SNAI2 promoter sequences. Dual-luciferase reporter assay was used to detect the gene promoter activation. Co-IP assay was conducted to verify the interaction of EGR1 and p300/CBP. RESULTS: EGR1 was highly expressed in pancreatic cancer rather than normal pancreatic tissues and correlated with poor prognosis and cancer metastasis. EGR1 was proved to enhance the migration and invasion ability of pancreatic cells. Besides, EGR1 was positively correlated with EMT process in pancreatic cancer, via a SNAI2-dependent pathway. P300/CBP was found to play an auxiliary role in the transcriptional activation of the SNAI2 gene by EGR1. Finally, in vivo experiments also proved that EGR1 promoted liver metastasis of pancreatic cancer. CONCLUSION: Our findings implied the EMT-promoting effect of EGR1 in pancreatic cancer and revealed the intrinsic mechanism. Blocking the expression of EGR1 may be a new anticancer strategy for pancreatic cancer.

Risk stratification of clinically relevant delayed gastric emptying after pancreaticoduodenectomy.

BACKGROUND: Delayed gastric emptying (DGE) remains one of the major complications after pancreaticoduodenectomy (PD), with discrepant reports of its contributing factors. This study aimed to develop a nomogram to identify potential predictors and predict the probability of DGE after PD. METHODS: This retrospective study enrolled 422 consecutive patients who underwent PD from January 2019 to December 2021 at our institution. The LASSO algorithm and multivariate logistic regression were performed to identify independent risk and protective factors associated with clinically relevant delayed gastric emptying (CR-DGE). A nomogram was established based on the selected variables. Then, the calibration curve, ROC curve, decision curve analysis (DCA), and clinical impact curve (CIC) were applied to evaluate the predictive performance of our model. Finally, an independent cohort of 45 consecutive patients from January 2022 to March 2022 was enrolled to further validate the nomogram. RESULTS: Among 422 patients, CR-DGE occurred in 94 patients (22.2%). A previous history of chronic gastropathy, intraoperative plasma transfusion ≥ 400 ml, end-to-side gastrointestinal anastomosis, intra-abdominal infection, incisional infection, and clinically relevant postoperative pancreatic fistula (CR-POPF) were identified as risk predictors. Minimally invasive pancreaticoduodenectomy (MIPD) was demonstrated to be a protective predictor of CR-DGE. The areas under the curve (AUCs) were 0.768 (95% CI, 0.706-0.830) in the development cohort, 0.766 (95% CI, 0.671-0.861) in the validation cohort, and 0.787 (95% CI, 0.633-0.940) in the independent cohort. Then, we built a simplified scale based on our nomogram for risk stratification. CONCLUSIONS: Our study identified seven predictors and constructed a validated nomogram that effectively predicted CR-DGE for patients who underwent PD.

CHRNB2 represses pancreatic cancer migration and invasion via inhibiting ß-catenin pathway.

BACKGROUND: Pancreatic cancer is one of the most lethal disease with highly fatal and aggressive properties. Lymph node ratio (LNR), the ratio of the number of metastatic lymph nodes to the total number of examined lymph nodes, is an important index to assess lymphatic metastasis and predict prognosis, but the molecular mechanism underlying high LNR was unclear. METHODS: Gene expression and clinical information data of pancreatic cancer were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Patients in TCGA were averagely divided into low and high LNR groups. Then, Weighted Gene Co-expression Network Analysis (WGCNA) was utilized to build co-expression network to explore LNR-related modules and hub genes. GO and KEGG analysis was performed to find key pathways related to lymph node metastasis. Next, GSE101448 and the overall survival data in TCGA was employed to further select significant genes from hub genes. Considering the key role of CHRNB2 in LNR and survival, gene set enrichment analysis (GSEA) was applied to find pathways related to CHRNB2 expression in pancreatic cancer. The contribution of CHRNB2 to migrative and invasive ability of pancreatic cancer cells was confirmed by Transwell assays. We finally explored the role of CHRNB2 in EMT and ß-catenin pathway via Western Blot. RESULTS: High LNR was significantly related to high T stages and poor prognosis. In WGCNA, 14 hub genes (COL5A1, FN1, THBS2, etc.) were positively related to high LNR, 104 hub genes (FFAR1, SCG5, TMEM63C, etc.) were negatively related to high LNR. After taking the intersection with GSE101448, 13 genes (CDK5R2, SYT7, CACNA2D2, etc.) which might prevent lymph node metastasis were further selected. Among them, CHRNB2 showed the strongest relationship with long survival. Moreover, CHRNB2 also negatively related to the T stages and LNR. Next, knockdown of CHRNB2 expression could acetylcholine (ACh)-independently increase the migration and invasion of pancreatic cancer cells, while CHRNB2 overexpression ACh-independently decrease the migration and invasion of pancreatic cancer cells. For exploring the underlying mechanism, CHRNB2 downregulated ß-catenin pathway might through controlling its upstream regulators such as SOX6, SRY, SOX17, and TCF7L2. CONCLUSIONS: CHRNB2 negatively relates to lymph node metastasis in pancreatic cancer patients. CHRNB2 could inhibit ß-catenin pathway, EMT, migration and invasion of pancreatic cancer cells via ACh-independent mechanism.

Multidrug resistance genes screening of pancreatic ductal adenocarcinoma based on sensitivity profile to chemotherapeutic drugs.

BACKGROUNDS: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types and chemotherapeutic drug resistance is a stumbling block in improving the overall survival of PDAC patients. The nature of specific drug resistant subpopulation within pancreatic ductal adenocarcinoma is believed to be partly attributed to epithelial-mesenchymal transition (EMT) and cell stemness. Various PDAC cell lines show various degrees of resistance to chemotherapeutic agents including gemcitabine (GEM) and 5-fluorouracil (5-FU). In-depth understanding of drug resistance mechanisms and profile heterogeneities could lead to the development of novel and precise therapeutic strategies for addressing the chemo-resistant dilemma in PDAC patients. METHODS: Cytotoxicity assays were performed by CCK8 in ten common PDAC cell lines including AsPC-1, BxPC-3, CAPAN-1, CFPAC, HPAFII, MIA PaCa-2, PANC-1, Patu-8988, SW1990 and T3M4. RNA-seq data of the ten cell lines were downloaded from Cancer Cell Line Encyclopedia (CCLE) database and subsequently analyzed for differentially expressed genes (DEGs). Based on first-line chemotherapy regimens of PDAC, DEGs between resistant and sensitive cell lines were validated by qRT-PCR. Enriched pathways of differentially expressed genes between the resistant and sensitive cell lines were acquired by Metascape database. RESULTS: We found that the top two toxic drugs for PDAC cell lines were paclitaxel (PTX) and GEM. Among the ten PDAC cell lines, SW1990 was the most resistant PDAC cell line with the highest IC50 levels for three drugs, while MIA PaCa-2 and BxPC-3 were the most sensitive PDAC cell lines. Differential expression analysis revealed the highest number of DEGs associated with cisplatin (CIS) sensitivity up to 642 genes, of which 181 genes were upregulated and 461 genes were downregulated in CIS-resistant cell lines. The least number of DEGs are associated with GEM sensitivity, of which 37 genes were highly expressed in GEM-resistant PDAC cell lines and 25 genes were lowly expressed. Enrichment analysis of the DEGs revealed that pathways associated with drug resistance were mainly extracellular matrix and cell-cell junction related pathways. CONCLUSIONS: PDAC cell lines showed diverse sensitivities to commonly used chemotherapeutic agents, which was caused by differential gene expression between the resistant and sensitive cell lines. The heterogeneity and its associated genes were enriched in extracellular matrix and cell-cell junction related pathways. Our study first portrayed the sensitivity profile to chemotherapeutic drugs of PDAC, which would benefit the chemoresistance mechanism study by reemphasizing the vital role of extracellular matrix and cell-cell junction related pathways and helping the selection of suitable PDAC cell lines.

Mobius strip in pancreatic cancer: biogenesis, function and clinical significance of circular RNAs.

Pancreatic cancer (PC) is a kind of common digestive system cancer with the worst prognosis for its insidious symptoms and high invasiveness. Circular RNAs (circRNAs) are endogenous non-coding RNAs with covalently closed circular structure, which are more stable and conservative than linear RNAs and process major functions of microRNA (miRNA) sponge, RNA binding protein (RBP) sponge and polypeptide translation template. Incremental researches have proved that circRNAs express aberrantly and play a vital role in various types of cancer. Hence, we reviewed the biogenesis, degradation, characteristics, and biological functions of circRNAs and summarized the roles circRNAs played in the proliferation, invasion, metastasis, chemoresistance and exosome-mediated intercellular communication of PC. We then summed up a workflow regarding circRNA research in cancer and relative specific databases and experimental methods. In the future, more efforts ought to be put into circRNAs research in PC, including basic research of discovering and testifying circRNAs centered ceRNA networks, and clinical research of exploiting exosomal or circulating circRNAs as a diagnostic biomarker, chemotherapy sensitivity predictor and prognostic predictor.

IFIT1 modulates the proliferation, migration and invasion of pancreatic cancer cells via Wnt/ß-catenin signaling.

OBJECTIVES: Previously, Interferon-induced Protein with Tetratricopeptide Repeats 1 (IFIT1) has been shown to promote cancer development. Here, we aimed to explore the role of IFIT1 in the development and progression of pancreatic cancer, including the underlying mechanisms. METHODS: We explored IFIT1 expression in pancreatic cancer samples using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Cell Counting Kit-8 (CCK8), colony formation, scratch wound-healing and Transwell assays were performed to assess the proliferation, migration and invasion abilities of pancreatic cancer cells. Gene Set Enrichment Analysis (GSEA) and Western blotting were performed to assess the regulatory effect of IFIT1 on the Wnt/ß-catenin pathway. RESULTS: We found that upregulation of IFIT1 expression is common in pancreatic cancer and is negatively associated with overall patient survival. Knockdown of IFIT1 expression led to decreased proliferation, migration and invasion of pancreatic cancer cells. We also found that IFIT1 could regulate Wnt/ß-catenin signaling, and that a Wnt/ß-catenin agonist could reverse this effect. In addition, we found that IFIT1 can promote epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. CONCLUSIONS: Our data indicate that IFIT1 increases pancreatic cancer cell proliferation, migration and invasion by activating the Wnt/ß-catenin pathway. In addition, we found that EMT could be regulated by IFIT1. IFIT1 may serve as a potential therapeutic target for pancreatic cancer.

Visualization of nasal powder distribution using biomimetic human nasal cavity model.

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

Comparative assessment of Chinese mitten crab aquaculture in China: Spatiotemporal changes and trade-offs.

The increasing human demand for high-quality animal protein has provided impetus for the development of aquaculture. Chinese mitten crab (Eriocheir sinensis) is a catadromous species rapidly being cultured in China but scientific literature documenting its life cycle environmental and economic consequences remains scarce. This study aims to address this gap by examining the spatio-temporal evolution of crab aquaculture in China since the 2000s and evaluating the environmental and economic characteristics along its life-cycle stages: megalopa, juvenile crab, and adult crab cultivation. The geostatistical analysis shows a more dispersed pattern of crab aquaculture nationally as crab grows, with coastal provinces that have brackish water for megalopa cultivation but wider spatial coverage for juvenile and adult crab cultivation. Our findings reveal that the production of 1 ton of live-weight crab results in 7.65 ton of CO2 equivalent of greenhouse gas emissions, surpassing previous estimates for finfish fish production by approximately 50%. Most environmental pressures occur during the adult crab cultivation stage, with significant contributions from upstream processes such as electricity and feed production. By comparing between different production systems, our study shows that crab aquaculture in lake systems performs better than pond systems in terms of most global environmental impact categories and economic considerations. This work contributes to the existing literature by elucidating the spatio-temporal changes of crab aquaculture boom in China and constructing a representative life cycle data pool that broadens the benchmark knowledge on its environmental and economic characteristics. We highlight the trade-offs between environmental and economic performance as well as the balance between global and local environmental impacts to promote sustainable growth in the aquaculture industry.

STOML2 restricts mitophagy and increases chemosensitivity in pancreatic cancer through stabilizing PARL-induced PINK1 degradation.

Pancreatic cancer remains one of the most lethal diseases with a relatively low 5-year survival rate, and gemcitabine-based chemoresistance occurs constantly. Mitochondria, as the power factory in cancer cells, are involved in the process of chemoresistance. The dynamic balance of mitochondria is under the control of mitophagy. Stomatin-like protein 2 (STOML2) is located in the mitochondrial inner membrane and is highly expressed in cancer cells. In this study, using a tissue microarray (TMA), we found that high STOML2 expression was correlated with higher survival of patients with pancreatic cancer. Meanwhile, the proliferation and chemoresistance of pancreatic cancer cells could be retarded by STOML2. In addition, we found that STOML2 was positively related to mitochondrial mass and negatively related to mitophagy in pancreatic cancer cells. STOML2 stabilized PARL and further prevented gemcitabine-induced PINK1-dependent mitophagy. We also generated subcutaneous xenografts to verify the enhancement of gemcitabine therapy induced by STOML2. These findings suggested that STOML2 regulated the mitophagy process through the PARL/PINK1 pathway, thereby reducing the chemoresistance of pancreatic cancer. STOML2-overexpression targeted therapy might be helpful for gemcitabine sensitization in the future.

Pancreatic cancer stemness: dynamic status in malignant progression.

Pancreatic cancer (PC) is one of the most aggressive malignancies worldwide. Increasing evidence suggests that the capacity for self-renewal, proliferation, and differentiation of pancreatic cancer stem cells (PCSCs) contribute to major challenges with current PC therapies, causing metastasis and therapeutic resistance, leading to recurrence and death in patients. The concept that PCSCs are characterized by their high plasticity and self-renewal capacities is central to this review. We focused specifically on the regulation of PCSCs, such as stemness-related signaling pathways, stimuli in tumor cells and the tumor microenvironment (TME), as well as the development of innovative stemness-targeted therapies. Understanding the biological behavior of PCSCs with plasticity and the molecular mechanisms regulating PC stemness will help to identify new treatment strategies to treat this horrible disease.

High-titer AAV disrupts cerebrovascular integrity and induces lymphocyte infiltration in adult mouse brain.

The brain is often described as an "immune-privileged" organ due to the presence of the blood-brain-barrier (BBB), which limits the entry of immune cells. In general, intracranial injection of adeno-associated virus (AAV) is considered a relatively safe procedure. In this study, we discovered that AAV, a popular engineered viral vector for gene therapy, can disrupt the BBB and induce immune cell infiltration in a titer-dependent manner. First, our bulk RNA sequencing data revealed that injection of high-titer AAV significantly upregulated many genes involved in disrupting BBB integrity and antiviral adaptive immune responses. By using histologic analysis, we further demonstrated that the biological structure of the BBB was severely disrupted in the adult mouse brain. Meanwhile, we noticed abnormal leakage of blood components, including immune cells, within the brain parenchyma of high-titer AAV injected areas. Moreover, we identified that the majority of infiltrated immune cells were cytotoxic T lymphocytes (CTLs), which resulted in a massive loss of neurons at the site of AAV injection. In addition, antagonizing CTL function by administering antibodies significantly reduced neuronal toxicity induced by high-titer AAV. Collectively, our findings underscore potential severe side effects of intracranial injection of high-titer AAV, which might compromise proper data interpretation if unaware of.

Prognostic value and immune infiltration of ARMC10 in pancreatic adenocarcinoma via integrated bioinformatics analyses.

Background: Armadillo repeat-containing 10 (ARMC10) is involved in the progression of multiple types of tumors. Pancreatic adenocarcinoma (PAAD) is a lethal disease with poor survival and prognosis. Methods: We acquired the data of ARMC10 in PAAD patients from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) datasets and compared the expression level with normal pancreatic tissues. We evaluated the relevance between ARMC10 expression and clinicopathological factors, immune infiltration degree and prognosis in PAAD. Results: High expression of ARMC10 was relevant to T stage, M stage, pathologic stage, histologic grade, residual tumor, primary therapy outcome (P < 0.05) and related to lower Overall-Survival (OS), Disease-Specific Survival (DSS), and Progression-Free Interval (PFI). Gene set enrichment analysis showed that ARMC10 was related to methylation in neural precursor cells (NPC), G alpha (i) signaling events, APC targets, energy metabolism, potassium channels and IL10 synthesis. The expression level of ARMC10 was positively related to the abundance of T helper cells and negatively to that of plasmacytoid dendritic cells (pDCs). Knocking down of ARMC10 could lead to lower proliferation, invasion, migration ability and colony formation rate of PAAD cells in vitro. Conclusions: Our research firstly discovered ARMC10 as a novel prognostic biomarker for PAAD patients and played a crucial role in immune regulation in PAAD.

The underestimated importance of fertilizer in aquacultural phosphorus budget: Case of Chinese mitten crab.

China's reliance on aquaculture has intensified to satisfy the growing human demand for high-quality animal protein, making it the only country whose aquaculture production has greatly exceeded that of capture fishery for a long time. Previous studies have shown that phosphorus (P) is a limiting nutrient for freshwater eutrophication; therefore, the quantification of P flows in freshwater aquaculture is of great importance for improving aquaculture efficiency and reducing environmental pollution. In this study, life cycle assessment (LCA) and substance flow analysis (SFA) are combined to develop a life cycle P flow model for Chinese mitten crab (Eriocheir sinensis) culture and calculate the P inputs, outputs and net change in stock. The results show a relatively low P use efficiency (4 %) in Chinese mitten crab. Among all life-cycle stages, the maximum P input occurs during adult crab cultivation, when feed is continuously added to maintain appropriate nutrition levels and increase body weight. In addition, fertilizer is often neglected in the existing accounts but accounts for 24 % of the total P inputs. On the output side, approximately 86 % of the P accumulates in sediment, indicating the potential of sediment recycling as a nutrient source in agriculture. This study provides an updated quantitative method for describing nutrient flows within freshwater aquaculture systems and will contribute to decision-making in pollution control of intensive freshwater aquaculture activities.

Long Noncoding RNA and Circular RNA: Two Rising Stars in Regulating Epithelial-Mesenchymal Transition of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with especially poor prognosis. However, the molecular mechanisms of pancreatic oncogenesis and malignant progression are not fully elucidated. Epithelial-mesenchymal transition (EMT) process is important to drive pancreatic carcinogenesis. Recently, long noncoding RNAs (lncRNAs) and circular RNAs(circRNAs) have been characterized to participate in EMT in PDAC, which can affect the migration and invasion of tumor cells by playing important roles in epigenetic processes, transcription, and post-transcriptional regulation. LncRNAs can act as competing endogenous RNAs (ceRNA) to sequester target microRNAs(miRNAs), bind to the genes which localize physically nearby, and directly interact with EMT-related proteins. Currently known circRNAs mostly regulate the EMT process in PDAC also by acting as a miRNA sponge, directly affecting the protein degradation process. Therefore, exploring the functions of lncRNAs and circRNAs in EMT during pancreatic cancer might help pancreatic cancer treatments.

Chromatin Dynamics in Digestive System Cancer: Commander and Regulator.

Digestive system tumors have a poor prognosis due to complex anatomy, insidious onset, challenges in early diagnosis, and chemoresistance. Epidemiological statistics has verified that digestive system tumors rank first in tumor-related death. Although a great number of studies are devoted to the molecular biological mechanism, early diagnostic markers, and application of new targeted drugs in digestive system tumors, the therapeutic effect is still not satisfactory. Epigenomic alterations including histone modification and chromatin remodeling are present in human cancers and are now known to cooperate with genetic changes to drive the cancer phenotype. Chromatin is the carrier of genetic information and consists of DNA, histones, non-histone proteins, and a small amount of RNA. Chromatin and nucleosomes control the stability of the eukaryotic genome and regulate DNA processes such as transcription, replication, and repair. The dynamic structure of chromatin plays a key role in this regulatory function. Structural fluctuations expose internal DNA and thus provide access to the nuclear machinery. The dynamic changes are affected by various complexes and epigenetic modifications. Variation of chromatin dynamics produces early and superior regulation of the expression of related genes and downstream pathways, thereby controlling tumor development. Intervention at the chromatin level can change the process of cancer earlier and is a feasible option for future tumor diagnosis and treatment. In this review, we introduced chromatin dynamics including chromatin remodeling, histone modifications, and chromatin accessibility, and current research on chromatin regulation in digestive system tumors was also summarized.

Phospholipase A/acyltransferase 4 is a prognostic biomarker and correlated with immune infiltrates in pancreatic cancer.

Background: Phospholipase A/acyltransferase (PLAAT) family exhibits O- and N-acyltransferase activity and biosynthesize N-acylated ethanolamine phospholipids. Previously, PLAAT4 was seen as a tumor suppressor, but the exact function of PLAAT4 in pancreatic cancer was still unknown. In this study, we investigated the relationship of PLAAT4 and pancreatic cancer. Methods: Using the data from the cancer genome atlas (TCGA), Genotype-Tissue Expression (GTEx) database and Gene Expression Omnibus (GEO) datasets we compared the expression of PLAAT4 in normal and tumor tissues and analyzed the connections between PLAAT4 and several clinicopathological factors. Further, we conducted Gene ontology (GO) analysis, Gene set enrichment analysis (GSEA), single sample gene set enrichment analysis (ssGSEA) and estimate analysis to explore the association between PLAAT4 and biological function and immune infiltration. In addition, Kaplan-Meier (KM) analysis, univariate and multivariate Cox analysis were used to explore the association between PLAAT4 and prognosis. In addition, we plotted a nomogram according to the multivariate cox analysis visualizing the predictive ability of PLAAT4 on prognosis. In addition, we explore the influence of PLAAT4 on malignant behaviors of the pancreatic cancer cells in vitro. Results: After comparing the expression of PLAAT4 in normal and tumor tissues, we found that the expression of PLAAT4 was significantly high in pancreatic ductal adenocarcinoma (PDAC) samples. In addition, the results of GO and GSEA found that the expression of PLAAT4 was related to cell cycle checkpoints, M phase, regulation by p53, cell cycle mitotic and etc. Further, ssGSEA has shown that PLAAT4 was positively related to the abundance of aDC, Th1 cells, Th2 cells and negatively related to the Th17 cells. Subsequently, KM analysis, univariate and multivariate Cox analysis were used to analyze the correlation between PLAAT4 and prognosis. Additionally, we found that higher expression of PLAAT4 was related to T stage, N stage, histologic grade, etc (P < 0.05) and has a significant correlation with poor Overall Survival (OS), Disease-Specific Survival (DSS) and Progression-Free Interval (PFI). At last, we proved that PLAAT4 contributed to the malignant behaviors of the pancreatic cancer cells. Conclusion: This study indicated PLAAT4 as a novel prognostic biomarker and an important molecular that mediated immune response in pancreatic cancer.

Subcuticular Sutures versus Staples in Reducing Surgical Site Infections after Open Abdominal Digestive Surgery: A System Review and Meta-Analysis of Randomized Controlled Trials.

Background: Wound complications, primarily surgical site infections (SSIs), impose heavy a heavy burden on public health. This study aimed to compare the difference in the abilities of subcuticular sutures and staples to prevent SSIs after open abdominal surgery on the digestive system. Methods: A comprehensive search in Ovid-MEDLINE, Embase, Web of Science, and Cochrane Library (Central Register of Controlled Trials) was performed in January 2021. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PICOS (population, intervention, control, outcome, study type) model was applied to guide study selection and data extraction. Results: Six studies including 3,863 participants were included. According to analysis of SSI incidence, there was no obvious difference between the incidence of SSI when subcuticular sutures and staples were used (odds ratio [OR], 0.81; 95% confidence interval [CI], 0.61-1.08; p = 0.15). In the subsequent subgroup analysis of different operation procedures, the pooled results also failed to show significance for upper gastrointestinal surgery (OR, 1.09; 95% CI, 0.63-1.9; p = 0.75), lower gastrointestinal surgery (OR, 0.77; 95% CI, 0.56-1.05; p = 0.1), or hepatobiliary-pancreatic surgery (pooled OR, 0.72; 95% CI, 0.34-1.54; p = 0.4). Conclusions: Subcuticular sutures and staples did not show differences in their ability to prevent SSI incidence after open abdominal operation. These results require further verification by large-scale, high-quality randomized controlled trials.

IFIT1 modulates the proliferation, migration and invasion of pancreatic cancer cells via Wnt/ß-catenin signaling.

OBJECTIVES: Previously, Interferon-induced Protein with Tetratricopeptide Repeats 1 (IFIT1) has been shown to promote cancer development. Here, we aimed to explore the role of IFIT1 in the development and progression of pancreatic cancer, including the underlying mechanisms. METHODS: We explored IFIT1 expression in pancreatic cancer samples using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Cell Counting Kit-8 (CCK8), colony formation, scratch wound-healing and Transwell assays were performed to assess the proliferation, migration and invasion abilities of pancreatic cancer cells. Gene Set Enrichment Analysis (GSEA) and Western blotting were performed to assess the regulatory effect of IFIT1 on the Wnt/ß-catenin pathway. RESULTS: We found that upregulation of IFIT1 expression is common in pancreatic cancer and is negatively associated with overall patient survival. Knockdown of IFIT1 expression led to decreased proliferation, migration and invasion of pancreatic cancer cells. We also found that IFIT1 could regulate Wnt/ß-catenin signaling, and that a Wnt/ß-catenin agonist could reverse this effect. In addition, we found that IFIT1 can promote epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. CONCLUSIONS: Our data indicate that IFIT1 increases pancreatic cancer cell proliferation, migration and invasion by activating the Wnt/ß-catenin pathway. In addition, we found that EMT could be regulated by IFIT1. IFIT1 may serve as a potential therapeutic target for pancreatic cancer.