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, ...

a-simple-rapid-method-for-simultaneous-isolation-primary-islets

A Simple and Rapid Method for Simultaneous Isolation of Primary Islets and Primary Pancreatic Acinar Cells from Mice

In the research on the pathogenesis of post-acute pancreatitis diabetes mellitus (PPDM-A), abnormal bidirectional communication between pancreatic acinar ...

Naval Medical University

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.

Nanodrug delivery systems (NDDS) have demonstrated broad application prospects in disease treatment, prevention, and diagnosis due to several advantages, including functionalization capability, high drug-loading capacity, drug stability protection, and the enhanced permeability and retention (EPR) effect. However, their clinical translation still faces multiple challenges, including rapid clearance by the reticuloendothelial system (RES), poor targeting specificity, and insufficient efficiency in crossing biological barriers. To address these limitations, researchers have developed the biological carrier-mediated nanomedicine hitchhiking strategy (BCM-NHS), which leverages circulating cells, proteins, or bacteria as natural "mobile carriers" to enhance drug delivery. This approach enables nanocarriers to inherit the intrinsic biological properties, endowing them with immune evasion, prolonged circulation, dynamic targeting, biocompatibility, biodegradability, and naturally optimized biological interfaces. Here, a systematic overview of the BCM-NHS is provided. First, the review delves into the methods of nanoparticles (NPs) binding and immobilization, encompassing both the surface-attachment-mediated "backpack" strategy and the encapsulation-based "Trojan horse" strategy. Second, the classification of biological carriers, including both cell-based and non-cell-based carriers, is elucidated. Third, the physical properties and release mechanisms of these nanomaterials are thoroughly described. Finally, the latest applications of BCM-NHS in therapeutic and diagnostic contexts across various disease models including tumor, ischemic stroke, and pneumonia are highlighted.

Precision-Guided Stealth Missiles in Biomedicine: Biological Carrier-Mediated Nanomedicine Hitchhiking Strategy.

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.

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.

Potential effects of MPs and their co-pollutants on human intestinal tract.

Microplastics (MPs), as a kind of emerging pollutant, have attracted widespread attention. The effects of MPs of different diameter sizes on chronic pancreatitis and their underlying mechanisms remain to be explored. Therefore, we established a mouse chronic pancreatitis model exposed to two-diameter polystyrene particles (2 or 0.5 μm) for 6 weeks. We found that MPs exposure resulted in severe pancreatic fibrosis in mice, which was negatively correlated with particle size. In-depth mechanistic exploration revealed that after exposure to MPs, MPs can enter pancreatic stellate cells through the cell membrane, stimulate the activation of cellular ROS, further activate the NF-κB and TGF-β signaling pathways, and increase the levels of fibrotic proteins and collagen. The pancreatic fibrosis can be reversed by the ROS inhibitor N-acetyl cysteine (NAC). Meanwhile, oral intake of polystyrene particles in chronic pancreatic mice also affected the diversity of intestinal bacteria, downregulating the bacteria in the Bacteroidota phylum and upregulating the bacteria in the Verrucomicrobiota phylum, which could be another potential mechanism underlying the pathogenic effect of pancreatic fibrosis. Our findings reveal the adverse effects of MPs on chronic pancreatitis through inducing cellular ROS, activating pancreatic stellate cells and altering gut microbes.

Oral Ingestion of Polystyrene Microplastics Aggravates Chronic Pancreatitis Through ROS Induced NF-κb/TGF-β Signaling Pathway and Alteration of Gut Microbiota.

Exocrine and endocrine disorders and insufficiency are two major harmful pathological processes in chronic pancreatitis (CP) and can lead to steatorrhea and diabetes. However, there is a lack of reliable clinical classification schemes for evaluating the severity of exocrine and endocrine disorders in CP, and the underlying mechanisms are also unclear. In particular, exosome-based liquid biopsy and classification in CP are lacking. Here, we performed transcriptome sequencing on plasma exosomes from CP patients with different degrees of CP severity. Additionally, we analyzed single-cell sequencing data from pancreatic lesions in CP patients to interpret the classification, and an external cohort was established to verify the classification. Ultimately, we established and preliminarily verified a 3-stage classification system to predict steatorrhea and diabetes onset in CP patients based on the expression of 12 miRNAs in plasma exosomes. A publicly-available online tool implementing this classification system was also developed. Further analysis, in combination with single-cell sequencing data from CP mice, identified exosome-derived miR-24-3p and neutrophil S100A8 as pivotal factors in CP progression. Mechanistically, our findings suggest that downregulated exosome-derived miR-24-3p in CP may lead to the upregulation of its target gene, S100A8, in neutrophils, thus promoting CP-related exocrine and endocrine disorders by activating the fibrotic phenotype of pancreatic stellate cells and inducing inflammation in macrophages, leading to the apoptosis of pancreatic β cells. Together, our work provides a novel exosome-based 3-stage classification system for CP and highlights the role of exosomal miR-24-3p and S100A8 in fibrosis and pancreatic β-cell apoptosis.

Integrated transcriptome profiling of plasma exosomes reveals molecular stratification of exocrine and endocrine disorders and S100A8-mediated cell interactions in chronic pancreatitis.

ArticleTotal : 2	Year
Publication title	2025
Publication title	2026

Article	Year
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
Precision-Guided Stealth Missiles in Biomedicine: Biological Carrier-Mediated Nanomedicine Hitchhiking Strategy. Advanced science (Weinheim, Baden-Wurttemberg, Germany)\| PubMed ID: 40345158	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
Potential effects of MPs and their co-pollutants on human intestinal tract. Reviews on environmental health\| PubMed ID: 41150603	2025
Oral Ingestion of Polystyrene Microplastics Aggravates Chronic Pancreatitis Through ROS Induced NF-κb/TGF-β Signaling Pathway and Alteration of Gut Microbiota. FASEB journal : official publication of the Federation of American Societies for Experimental Biology\| PubMed ID: 41239787	2025
Integrated transcriptome profiling of plasma exosomes reveals molecular stratification of exocrine and endocrine disorders and S100A8-mediated cell interactions in chronic pancreatitis. Cell discovery\| PubMed ID: 41249153	2025

Zhenghui Yang

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