Pancreatic fibrosis is the dominant reversible pathological change and diagnostic factor in early chronic pancreatitis, defined by a mechanistic approach proposed in 2016. Main guidelines for chronic pancreatitis were published by the American Pancreas Association in 2014, the Japanese Society of Gastroenterology in 2015, and United European Gastroenterology in 2017. All three sets of guidelines mentioned that the staging of chronic pancreatitis is important but challenging. There are various image modalities for the non-histologic diagnosis of pancreatic fibrosis: (1) shear wave elastography, such as an acoustic radiation force impulse with a cut-off value of 1.4 m/s; (2) strain elastography using grades of strain; (3) endoscopic ultrasonography using the Rosemont criteria or endoscopic ultrasound criteria for early chronic pancreatitis proposed by the Japan Pancreas Society; (4) computed tomography using the Hounsfield scale or number of micro-calcifications; and (5) magnetic resonance imaging using the apparent diffusion coefficient and the T1w flash and T2w HASTE sequences. The clinical applications are to (1) evaluate pancreatic tumors and inflammatory disease; (2) monitor dyspepsia with early chronic pancreatitis; (3) monitor individuals with a high risk of pancreatic cancer; (4) analyze a fatty pancreas with fibrosis; (5) predict a fistula after pancreatic surgery; and (6) predict outcomes for chronic pancreatitis or pancreatic cancer. The selection of tools will be dependent on the clinical scenario. Conclusion: There are various modalities for the non-histologic diagnosis of pancreatic fibrosis. The selection of the optimal device will be dependent on the clinical scenario.

Obesity is closely linked to metabolic diseases, particularly non-alcoholic steatohepatitis (NASH) or non-alcoholic fatty liver disease (NAFLD), ultimately leading to hepatocellular carcinoma (HCC). However, the molecular mechanisms of NASH-associated HCC (NAHCC) remain elusive. To explore the impact of Max dimerization protein 3 (MXD3), a transcription factor that regulates several cellular functions in disorders associated with metabolic diseases, we conditionally expressed Mxd3 proteins using Tet-on mxd3 transgenic zebrafish (MXs) with doxycycline (MXs + Dox) or without doxycycline (MXs − Dox) treatment. Overexpression of global MXD3 (gMX) or hepatic Mxd3 (hMX) was associated with obesity-related NAFLD pathophysiology in gMX + Dox, and liver fibrosis and HCC in hMX + Dox. Oil Red O (ORO)-stained signals were seen in intravascular blood vessels and liver buds of larval gMX + Dox, indicating that Mxd3 functionally promotes lipogenesis. The gMX + Dox-treated young adults exhibited an increase in body weight and visceral fat accumulation. The hMX + Dox-treated young adults showed normal body characteristics but exhibited liver steatosis and NASH-like phenotypes. Subsequently, steatohepatitis, liver fibrosis, and NAHCC were found in 6-month-old gMX + Dox adults compared with gMX − Dox adults at the same stage. Overexpression of Mxd3 also enhanced AR expression accompanied by the increase of AR-signaling pathways resulting in hepatocarcinogenesis in males. Our results demonstrate that global actions of Mxd3 are central to the initiation of obesity in the gMX zebrafish through their effects on adipogenesis and that MXD3 could serve as a therapeutic target for obesity-associated liver diseases.

A new concept for the diagnosis and management of non-functional dyspepsia in guidelines was lacking in the past decade. Medical advancement has proven pancreatic fibrosis (essential image evidence of early chronic pancreatitis) to be a cause of dyspepsia and related to pancreatic exocrine dysfunction. This study aimed to analyze the clinical picture, biomarker, and percentage of pancreatic fibrosis in the dyspeptic population. A total of 141 consecutive patients were retrospectively enrolled. They were diagnosed with peptic ulcer disease, 9.2% (n = 13); pancreatic fibrosis, 17% (n = 24); pure Helicobacter pylori infection, 19.9% (n = 28); functional dyspepsia, 53.2% (n = 75); and chronic pancreatitis, 0.7% (n = 1). Among those with pancreatic fibrosis, (n = 24), 11 were diagnosed on the basis of a pancreatic acoustic radiation force impulse exceeding 1.4 m/s, and the remaining 13 were diagnosed with early chronic pancreatitis with at least three of the Japanese endoscopic ultrasonography criteria. The anatomic distribution of parenchymal criteria of early chronic pancreatitis was head, 53%; body, 38%; and tail, 9%. There were 17 cases (71%, 17/24) without Helicobacter pylori and whose dyspepsia improved after pancreatic enzyme replacement with a ratio of 82.3% (14/17). Of the 141 cases, 19 received gastric emptying scintigraphy and Western blot analysis of chromogranin-A in duodenal mucosa. Delayed gastric emptying was more common in functional dyspepsia and chromogranin-A was expressed more in pancreatic fibrosis. In conclusion, pancreatic fibrosis (including early chronic pancreatitis) outnumbered peptic ulcer disease in the dyspeptic population and pancreatic enzyme therapy was effective for 82% of cases. In early chronic pancreatitis, pancreatic fibrosis is dominant in the head location, and duodenum mucosa chromogranin-A is a potential biomarker with increased expression in an age-matched manner.

Copper contamination in coastal water environments poses a significant health risk, and traditional treatments for copper intoxication include gastric lavage, chelation, and hemodialysis. Recent research suggests that probiotics may help mitigate heavy metal toxicity by promoting biosorption in the intestinal tract. To explore this potential, we investigated the protective effects of Heyndrickxia coagulans (H. coagulans) against copper-induced toxicity in rats. After eight weeks of exposure, rats receiving both copper and H. coagulans exhibited significant improvements in renal function, lipid profiles, antioxidant enzyme activity, and histological markers compared to the copper-only group. However, liver function remained largely unchanged, suggesting a more pronounced protective effect on renal health. These findings highlight the potential of H. coagulans as a supportive intervention for mitigating the adverse effects of copper intoxication.

During liver injury, early pathological changes may go unnoticed, delaying the diagnosis until the disease has advanced to stages such as fibrosis, cirrhosis, or hepatocellular carcinoma. Hepatic fibrosis is a sign of long-term liver injury that leads toward permanent liver damage. It involves the buildup of too much extracellular matrix (ECM) and is activated by hepatic stellate cells (HSCs). The transforming growth factor-β1 (TGF-β1)/SMAD pathway is central to this process, which shows great potential for therapeutic strategies. Therefore, we investigated the therapeutic potential of microRNA (miRNA)-mediated regulation of fibrogenesis by using zebrafish models. A group of fibrosis-related miRNAs was identified and used to generate transgenic zebrafish lines. Fibrosis was induced via doxycycline (DOX)-controlled overexpression of TGF-β1a, and the antifibrotic efficacy of miRNAs was evaluated. Quantitative real-time PCR showed a marked downregulation of the target miRNAs, accompanied by decreased expression of fibrotic markers. Next, we confirmed that TGF-β1a, GREM1, and α-SMA protein levels were decreasing. Histological staining revealed improved liver structure and diminished collagen deposition. These findings indicate that through manipulating the miRNA expressions, we can effectively disrupt TGF-β-induced fibrogenesis, inactivate HSC, inhibit ECM remodeling, and attenuate liver fibrosis, and highlight the potential of miRNA-based therapeutic strategies for early intervention in liver disease. Key messages: Establishment of an in vivo model for developing an inducible miRNA expression system in zebrafish. Predicting and evaluating targeted miRNAs that attenuate TGF-β-induced hepatic fibrosis. Elucidate the potential mechanism for fibrosis that may be a strategy for future therapies. Graphical MicroRNA-mediated modulation attenuates hepatic fibrosis by coordinately suppressing the TGF-β/SMAD signaling pathway, hepatic stellate cell activation, and extracellular matrix deposition. Protein-level validation confirms reduced phosphorylation of Smad2 and decreased expression of key fibrotic markers, including α-SMA, collagen I, and fibronectin. These findings highlight a multi-target regulatory mechanism through which miRNAs exert antifibrotic effects at the systems level.

Background: Prior research has reported increased expression of duodenal chromogranin-A (CgA), secreted by enteroendocrine cells (EECs), in association with pancreatic fibrosis. However, it remains unknown whether serum CgA levels are also elevated, and whether there is a different distribution pattern of EECs in pancreatic fibrosis and other dyspeptic causes. Aims: This study had three main objectives. First, to compare the serum CgA level between patients with pancreatic fibrosis and those with other dyspeptic conditions. Second, to analyze the distribution pattern of duodenal EECs. Third, to evaluate whether biopsy results varied depending on the specific location within the duodenum. Serum CgA levels were categorized into low and high groups based on a cutoff value of 50 ng/mL. Methods: This cross-sectional prospective case series included 15 patients, with 4 patients in the low CgA group and 11 in the high CgA group. Each participant underwent a serum CgA test, transabdominal ultrasonography, pancreatic elastography, and upper gastrointestinal endoscopy. During endoscopy, a single gastric biopsy and three duodenal biopsies from different locations were obtained. Results: Patients in the high CgA group were generally older (52–68 years) than those in the low CgA group (37–55 years), with a statistically significant difference (p < 0.01). The high CgA group exhibited a clustered and centralized pattern of EECs, whereas the low CgA group showed a more discrete pattern with fewer EECs (p < 0.01). All duodenal ulcer cases were found in the low CgA group, while three cases of pancreatic fibrosis and one case of chronic pancreatitis were identified in the high CgA group. In the high CgA group, five cases of functional dyspepsia showed a band-like EEC distribution pattern, whereas cases with pancreatic fibrosis demonstrated a more uniformly scattered EEC distribution (p < 0.01). Consistency among intra-individual duodenal biopsy results was high across different biopsy sites. Conclusions: Elevated serum CgA (>50 ng/mL) and specific duodenal EEC distribution patterns may serve as potential diagnostic indicators for pancreatic fibrosis or chronic pancreatitis. These characteristics could help differentiate these conditions from functional dyspepsia.