an-obstructive-chronic-pancreatitis-model-established-through

An Obstructive Chronic Pancreatitis Model Established Through Electrocoagulation

Chronic pancreatitis (CP) is a severe inflammatory condition that can destroy the pancreas, lead to diabetes, and increase pancreatic cancer risk, ...

Naval Medical University

The current study aimed to develop a new chronic pancreatitis and spontaneous pancreatic cancer model on C57/BL6 mouse through retrograde pancreatic duct injection of dibutyltin dichloride (DBTC) and explore its basic pathological changes as compared to the previous published chronic pancreatitis model through tail vein injection of DBTC with alcohol drinking. C57/BL6 mice were randomly divided into 3 groups: CG (control group; n = 15), VG (tail vein injection of DBTC (8 mg/kg) with 10% alcohol drinking group; n = 20), and PG (retrograde pancreatic duct injection of DBTC group (1 mg/kg); n = 30). Five mice in each group were sacrificed at a specific time point after the first treatment. The pathological section was observed. The activities of amylase, bilirubin, and hyaluronic acid in serum were determined. The expression of fibronectin, COL1A1, α-SMA, MMP-1, and TIMP-1 in the pancreas was assayed. Severe fibrosis of the pancreas with inflammatory cell infiltration could be observed on day 21 in the PG. In the VG, slight fibrosis of the pancreas with inflammatory cell infiltration was observed on day 28. There were significant differences in serum amylase, bilirubin, and hyaluronic acid levels between the PG and VG. The protein level of COL1A1 and α-SMA significantly increased in the PG. The mRNA expression of TIMP-1 is upregulated and the MMP-1 mRNA level is downregulated in the PG. Finally, typical neoplastic pathological change is significantly obvious in the PG. In conclusion, we established and validated a new chronic pancreatitis (CP) and spontaneous pancreatic cancer mouse model through retrograde injection of DBTC into the pancreatic duct. Previously reported mouse model through tail vein injection of DBTC with alcohol drinking could not cause obvious CP and neoplastic pathological change in mice.

Methods of a New Chronic Pancreatitis and Spontaneous Pancreatic Cancer Mouse Model Using Retrograde Pancreatic Duct Injection of Dibutyltin Dichloride.

Pancreatic adenosquamous carcinoma (ASPC) is a rare subtype of pancreatic cancer with lethal malignancy, and few studies have focused on the heterogeneity of ASPC. Here, we performed a single-cell sequencing procedure on pancreatic tumor tissue from an ASPC patient and a patient with high-grade intraductal papillary mucinous neoplasm (IPMN). Through the combined analysis of single-cell sequencing data from five pancreatic ductal adenocarcinoma (PDAC) patients, one IPMN patient, and one ASPC patient in a public database, we identified 11 main types of cells, including macrophages, B cells, cancer stem cells, ductal cells, fibroblasts, endo/stellate cells, neutrophils, acinar cells, T cells, natural killer (NK) cells, dendritic cells, and mast cells. Then, the different characteristics and differentiation paths of the immune microenvironment among IPMN, ASPC, and PDAC in macrophages, T cells, and cancer-associated fibroblasts (CAFs) were identified through multiple bioinformatics analyses. Two novel special cancer-associated fibroblasts were identified as nCAFs and imCAFs. Then, cancer cells in duct cells were identified using the infercnv software. Two ASPC-specific subgroups of cancer cells with squamous cell features were identified. Finally, the identified specific CAFs and cancer cells were mapped to TCGA-PAAD cohort through the cibersoftx software. All of these identified subgroups were calculated to have a significant prognostic value in pancreatic cancer patients. These findings will promote the clinical application of single-cell sequencing data of pancreatic cancer and deepen our understanding of ASPC.

Single-cell sequencing reveals heterogeneity between pancreatic adenosquamous carcinoma and pancreatic ductal adenocarcinoma with prognostic value.

Ubiquitous pollution due to microplastics through the food chain is a major cause of various deleterious effects on the human health. The aim of this study was to determine the existence of microplastics and the internal mechanism of microplastics as accelerators of cholelithiasis. Gallstones were collected from 16 patients after cholecystectomy, and microplastics in the gallstones were detected through laser direct infrared and pyrolysis gas chromatographymass spectrometry examinations. Mice model of gallstone were constructed with or without different diameters of microplastic (0.5, 5 and 50 µm). The affinity between microplastic and cholesterol or bilirubin was tested by co-culturing and qualified using molecular dynamics simulations. Finally, altered gut microbiota among the groups were identified using 16 s rRNA sequencing. The presence of microplastics in the gallstones of all the patients were confirmed. Microplastic content was significantly higher in younger chololithiasis patients (age<50 years). Mice fed a high-cholesterol diet with microplastic drinks showed more severe chololithiasis. In terms of the mechanism, microplastics showed a higher affinity for cholesterol than for bilirubin. Significant alterations in the gut microbiota have also been identified after microplastic intake in mice. Our study revealed the presence of microplastics in human gallstones, showcasing their potential to aggravate chololithiasis by forming large cholesterol-microplastic heteroaggregates and altering the gut microbiota.

Microplastics are detected in human gallstones and have the ability to form large cholesterol-microplastic heteroaggregates.

Editorial: Targeting key cellular signaling network for cancer chemotherapy and immunotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.

Single-cell RNA sequencing reveals the process of CA19-9 production and dynamics of the immune microenvironment between CA19-9 (+) and CA19-9 (-) PDAC.

Artificial intelligence (AI) is an epoch-making technology, among which the 2 most advanced parts are machine learning and deep learning algorithms that have been further developed by machine learning, and it has been partially applied to assist EUS diagnosis. AI-assisted EUS diagnosis has been reported to have great value in the diagnosis of pancreatic tumors and chronic pancreatitis, gastrointestinal stromal tumors, esophageal early cancer, biliary tract, and liver lesions. The application of AI in EUS diagnosis still has some urgent problems to be solved. First, the development of sensitive AI diagnostic tools requires a large amount of high-quality training data. Second, there is overfitting and bias in the current AI algorithms, leading to poor diagnostic reliability. Third, the value of AI still needs to be determined in prospective studies. Fourth, the ethical risks of AI need to be considered and avoided.

The application of artificial intelligence in EUS.

Previous research has shown that the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in macrophages can promote severe acute pancreatitis through the release of inflammatory factors. The role of this pathway in pancreatic acinar cells, however, has not been studied, and understanding its mechanism could be crucial. We analysed plasma from 50 acute pancreatitis (AP) patients and 10 healthy donors using digital PCR, which links mitochondrial DNA (mtDNA) levels to the severity of AP. Single-cell sequencing of the pancreas during AP revealed differentially expressed genes and pathways in acinar cells. Experimental studies using mouse and cell models, which included mtDNA staining and quantitative PCR, revealed mtDNA leakage and the activation of STING-related pathways, indicating potential inflammatory mechanisms in AP. In conclusion, our study revealed that the mtDNA-STING-nuclear factor κB(NF-κB) pathway in pancreatic acinar cells could be a novel pathogenic factor in AP.

Mitochondrial DNA Leakage Promotes Persistent Pancreatic Acinar Cell Injury in Acute Pancreatitis via the cGAS-STING-NF-κB Pathway.

Autoimmune pancreatitis (AIP) is identified as a severe chronic immune-related disorder in pancreas, including two subtypes. In this study, pancreatic lesions in patients diagnosed as either type 1 AIP or type 2 AIP are examined, and these patients' peripheral blood at single-cell level. Furthermore, flow cytometry, immunofluorescence, and functional assays are performed to verify the identified cell subtypes. In type 1 AIP, there is a notable increase in the amount of B cells and plasma cells, and IgG4+ plasma cells are key pathogenic cells of AIP. The differentiation path of naïve-stage B cells into IgG4+ produced plasma cells is observed, and an increased amount of T helper cells and T follicular helper (Tfh) cells. This study also reveals that HIF-1α, an activated transcriptional factor, can directly bind to promoter site of NAMPT, promoting higher levels of visfatin production in HIF1A+ classical monocytes. Pancreatic stellate cells can be activated by extracellular visfatin and promote the development of fibrotic response in pancreatic lesions across both AIP subtypes. The current findings shed light on the exploration of dynamic alterations in peripheral blood cells and cell subgroups in pancreatic lesions of AIP, while elucidating a pathogenic cell subset and potential fibrosis mechanism of AIP.

Unraveling the Microenvironment and the Pathogenic Axis of HIF-1α-Visfatin-Fibrosis in Autoimmune Pancreatitis Using a Single-Cell Atlas.

Diet therapy can help alleviate chronic pancreatitis symptoms. The quality of diet therapy content in Internet videos varies markedly. Evaluating and assessing these videos is crucial for providing reliable patient education. This study aims to analyze 102 Internet videos regarding dietary therapy for chronic pancreatitis on media platforms in China (Bilibili, Weibo, and Tiktok) and rate their content, reliability, and quality. Videos were categorized into 3 sources: hospital or university officials, medical doctors, and independent users. An 8-point scale was used to score content (smoking, drinking, eating frequency, overeating, and nutrient intake [high-quality protein, low fat, nutrition, and dietary fiber]). An adapted DISCERN tool was used to assess reliability, with the Global Quality Scale employed to measure quality. Among the 102 videos analyzed, 34 (4, 9, and 21 from hospital or university officials, medical doctors, and independent users, respectively) were rated as low quality, 37 (8, 12, and 17 from hospital or university officials, medical doctors, and independent users, respectively) were rated as moderate quality, and 31 (7, 19, and 6 from hospital or university officials, medical doctors, and independent users, respectively) were rated as high quality. Thus, among 102 videos from TikTok, Weibo, and Bilibili, only 31 (30.4%) were considered high quality based on reliability and quality assessments, and some were misleading. Our findings suggest nearly 70% of health videos fail to meet high-quality standards, highlighting critical needs for improved content moderation across media platforms. Medical professionals and institutions should be encouraged to produce more high-quality Internet videos with comprehensive content to better guide and support patients with pancreatitis in adopting effective dietary therapy.

Investigation and quality evaluation of Internet videos related to diet therapy for chronic pancreatitis.

Neutrophils can undergo transcriptional and epigenetic reprogramming in disease, thus causing inflammation or modulating tissue repair and fibrosis. A thorough understanding of the neutrophil subpopulation composition and their polarization processes in acute pancreatitis (AP) is essential to open up design of treatments tailored to individual patients. Herein, this study distinct subgroups and two differentiation pathways associated with N1 and N2 polarization during AP by single-cell sequencing. Inspired by this, a hollow manganese dioxide (HMnO)-based nanoreactor (Pyp@APHM) conjugated with neutrophil-binding Ly-6G antibody and loaded with porphyrin is developed for targeted and in situ modulation of neutrophil polarization. Pyp@APHM can enrich the AP site by hitchhiking on neutrophils and then degrade in response to a weakly acidic environment to simultaneously release manganese ions and porphyrin ligands, enabling in situ synthesis of manganese porphyrin antioxidants. Leveraging this strategy, Pyp@APHM can effectively eliminate reactive oxygen species (ROS) and broadly inhibit both N1 and N2 polarization, as well as enhance tissue oxygenation by generating O, thereby further mitigating pancreatic inflammation. This study provides a comprehensive single-cell atlas of neutrophils in AP and proposes an innovative hitchhiking therapeutic strategy for AP by restricting ROS in neutrophils.

A Single-Cell Atlas-Inspired Hitchhiking Therapeutic Strategy for Acute Pancreatitis by Restricting ROS in Neutrophils.

Nanodrug delivery systems (NDDSs) have demonstrated broad application prospects in disease treatment, prevention, and diagnosis due to their nanoscale size advantages and high drug-loading capacity. However, their clinical translation still faces multiple challenges, including rapid clearance by the reticuloendothelial system (RES), nonspecific targeting, and insufficient efficiency in crossing biological barriers. Cell membrane-coated biomimetic delivery systems (CMC-BDS), which integrates natural cell membranes onto nanoparticle (NPs) surfaces, provides nanodrugs with a versatile "biomimetic cloak," representing a highly promising surface engineering strategy. This approach enables nanocarriers to inherit the intrinsic biological properties of different cell sources, endowing them with immune evasion, prolonged circulation, dynamic targeting, biocompatibility, and biodegradability, while supporting the integration of diverse biomedical functions. Furthermore, surface functionalization modifications can enhance their programmability, multifunctionality, and biointerface adaptability, thereby optimizing targeted delivery efficiency and extending in vivo circulation time. This review first outlines the development and key preparation steps of cell membrane coating technology. It then discusses the selection strategies for various cell membrane types-including leukocyte, erythrocyte, platelet, dendritic cell, tumor cell, and bacterial membranes-while comparing their respective advantages and limitations. Finally, the review highlights recent advances in applying cell membrane-coated nanoparticles (CMC-NPs) for treating tumors, ischemic stroke, and inflammatory diseases.

Stealth missiles with precision guidance: A novel multifunctional nano-drug delivery system based on biomimetic cell membrane coating technology.

Cancer-associated fibroblasts (CAFs) are critical components of the tumor microenvironment (TME) and have important roles in carcinogenesis and metastasis by facilitating cancer cell proliferation, angiogenesis, extracellular matrix (ECM) remodeling, and drug resistance. The purpose of this study is to extensively describe CAFs in esophageal cancer (ESCA) and develop a CAF-based prognostic risk score to predict clinical outcomes in patients with ESCA.

RGS16-driven cancer-associated fibroblasts promote esophageal squamous cell carcinoma progression via the MDK-SDC1 axis-mediated intercellular crosstalk.

Microplastics (MPs), which are tiny plastic particles measuring less than 5 mm, have sparked public concern in recent years. When exposed to the environment, MPs absorb a variety of pollutants, leading to joint damage to human digestive system and other tissues. Human exposure to MPs mainly through food intake, resulting in potential risk of intestinal tract. Research have demonstrated that MPs compromise intestinal integrity and disrupt microbiota, as well as traverse into systemic circulation, posing threat to other tissues in our body. Morever, the MPs also serve as the "carrier" of the pollutants in the environment, such as organic compound, heavy metal and marine pollutant. The interaction between co-pollutants and MPs will influence their physical and chemical properties, producing dual toxic effects on intestinal system. However, the uptake and digestion process of MPs and their co-pollutants in the human body, the extent and mechanism of intestinal damage remain obscure. This review synthesizes current knowledge on MPs' uptake and digestion process in the gut, elucidating the pathogenesis of MPs and their co-pollutant induced damage on intestinal physical, microbiota and immune barrier.

Article	Year
Methods of a New Chronic Pancreatitis and Spontaneous Pancreatic Cancer Mouse Model Using Retrograde Pancreatic Duct Injection of Dibutyltin Dichloride. Frontiers in oncology\| PubMed ID: 35875076	2022
Single-cell sequencing reveals heterogeneity between pancreatic adenosquamous carcinoma and pancreatic ductal adenocarcinoma with prognostic value. Frontiers in immunology\| PubMed ID: 36052088	2022
Microplastics are detected in human gallstones and have the ability to form large cholesterol-microplastic heteroaggregates. Journal of hazardous materials\| PubMed ID: 38335610	2024
Editorial: Targeting key cellular signaling network for cancer chemotherapy and immunotherapy. Frontiers in immunology\| PubMed ID: 38803491	2024
Single-cell RNA sequencing reveals the process of CA19-9 production and dynamics of the immune microenvironment between CA19-9 (+) and CA19-9 (-) PDAC. Chinese medical journal\| PubMed ID: 38816396	2024
The application of artificial intelligence in EUS. Endoscopic ultrasound\| PubMed ID: 38947752	2024
Mitochondrial DNA Leakage Promotes Persistent Pancreatic Acinar Cell Injury in Acute Pancreatitis via the cGAS-STING-NF-κB Pathway. Inflammation\| PubMed ID: 39180578	2025
Unraveling the Microenvironment and the Pathogenic Axis of HIF-1α-Visfatin-Fibrosis in Autoimmune Pancreatitis Using a Single-Cell Atlas. Advanced science (Weinheim, Baden-Wurttemberg, Germany)\| PubMed ID: 39887620	2025
Investigation and quality evaluation of Internet videos related to diet therapy for chronic pancreatitis. Medicine\| PubMed ID: 40388769	2025
A Single-Cell Atlas-Inspired Hitchhiking Therapeutic Strategy for Acute Pancreatitis by Restricting ROS in Neutrophils. Advanced materials (Deerfield Beach, Fla.)\| PubMed ID: 40395143	2025
Stealth missiles with precision guidance: A novel multifunctional nano-drug delivery system based on biomimetic cell membrane coating technology. Materials today. Bio\| PubMed ID: 40528836	2025
RGS16-driven cancer-associated fibroblasts promote esophageal squamous cell carcinoma progression via the MDK-SDC1 axis-mediated intercellular crosstalk. Biology direct\| PubMed ID: 41094576	2025
Potential effects of MPs and their co-pollutants on human intestinal tract. Reviews on environmental health\| PubMed ID: 41150603	2025

Wanshun Li

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