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Background: Colorectal cancer (CRC) has a high incidence and mortality. Recent studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis, progression, and metastasis of CRC., Aim: To investigate the effect of indole-3-acetaldehyde (IAAD) on CRC., Methods: The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines (HCT116 and DLD-1). Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity tests. Cell apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium iodide. Invasiveness was investigated using the transwell assay. Western blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor (AhR) downstream genes. The PharmMapper, SEA, and SWISS databases were used to screen for potential target proteins of IAAD, and the core proteins were identified through the String database., Results: IAAD reduced tumorigenesis in a syngeneic mouse model. In CRC cell lines HCT116 and DLD1, IAAD exhibited cytotoxicity starting at 24 h of treatment, while it reduced Ki67 expression in the nucleus. The results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells, which may be related to the activation of AhR. IAAD can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 cells. At low concentrations (< 12.5 μmol/L), IAAD only exhibited cytotoxic effects without promoting cell invasion. In addition, predictions based on online databases, protein-protein interaction analysis, and molecular docking showed that IAAD can bind to matrix metalloproteinase-9 (MMP9), angiotensin converting enzyme (ACE), poly(ADP-ribose) polymerase-1 (PARP1), matrix metalloproteinase-2 (MMP2), and myeloperoxidase (MPO)., Conclusion: Indole-3-aldehyde can induce cell apoptosis and inhibit cell proliferation to prevent the occurrence of CRC; however, at high concentrations (≥ 25 μmol/L), it can also promote epithelial-mesenchymal transition and invasion in CRC cells. IAAD activates AhR and directly binds MMP9, ACE, PARP1, MMP2, and MPO, which partly reveals why it has a bidirectional effect., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Chronic liver disease (CLD) imposes a heavy burden on millions of people worldwide. Despite substantial research on the pathogenesis of CLD disorders, no optimal treatment is currently available for some diseases, such as liver cancer. Exosomes, which are extracellular vesicles, are composed of various cellular components. Exosomes have unique functions in maintaining cellular homeostasis and regulating cell communication, which are associated with the occurrence of disease. Furthermore, they have application potential in diagnosis and treatment by carrying diverse curative payloads. Hepatic macrophages, which are key innate immune cells, show extraordinary heterogeneity and polarization. Hence, macrophage-derived exosomes may play a pivotal role in the initiation and progression of various liver diseases. This review focuses on the effects of macrophage-derived exosomes on liver disease etiology and their therapeutic potential, which will provide new insights into alleviating the global pressure of CLD., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aim: To investigate the therapeutic efficacy and mechanisms of action of oncolytic-herpes-simplex-virus encoding granulocyte-macrophage colony-stimulating factor (HSV(GM-CSF)) in pancreatic carcinoma., Methods: Tumor blocks were homogenized in a sterile grinder in saline. The homogenate was injected into the right armpit of each mouse. After vaccination, the mice were randomly assigned into four groups: a control group, a high dose HSV(GM-CSF) group [1 × 10⁷ plaque forming units (pfu)/tumor], a medium dose HSV(GM-CSF) group (5 × 10⁶ pfu/tumor) and a low dose HSV(GM-CSF) group (5 × 10⁵ pfu/tumor). After initiation of drug administration, body weights and tumor diameters were measured every 3 d. Fifteen days later, after decapitation of the animal by cervical dislocation, each tumor was isolated, weighed and stored in 10% formaldehyde solution. The drug effectiveness was evaluated according to the weight, volume and relative volume change of each tumor. Furthermore, GM-CSF protein levels in serum were assayed by enzyme-linked immunosorbent assays at 1, 2, 3 and 4 d after injection of HSV(GM-CSF)., Results: Injection of the recombinant mouse HSV encoding GM-CSF resulted in a significant reduction in tumor growth compared to the control group, and dose-dependent effects were observed: the relative tumor proliferation rates of the low dose, medium dose and high dose groups on 15 d after injection were 45.5%, 55.2% and 65.5%, respectively. The inhibition rates of the tumor weights of the low, middle, and high dose groups were 41.4%, 46.7% and 50.5%, respectively. Furthermore, the production of GM-CSF was significantly increased in the mice infected with HSV(GM-CSF). The increase in the GM-CSF level was more pronounced in the high dose group compared to the other two dose groups., Conclusion: Our study provides the first evidence that HSV(GM-CSF) could inhibit the growth of pancreatic cancer. The enhanced GM-CSF expression might be responsible for the phenomenon.

Aim: To evaluate the multiple biomarkers of colorectal tumor and their potential usage in early diagnosis of colorectal cancers., Methods: Multiple biomarkers (DNA contents, AgNOR, PCNA, p53, c-erbB-2) in 10 normal colorectal mucosae, 37 colorectal adenomas and 55 colorectal cancers were analyzed quantitatively in the computed processing imaging system. Discrimination patterns were employed to evaluate the significance of single and multiple indices in diagnosis of colorectal cancers., Results: The mean values of the analyzed parameters increased in order of the normal mucosa, adenoma and adenocarcinoma, and this tendency reflected the progression of colorectal malignancy. The parameters including DNA index, positive rates, densities of AgNOR, c-erbB-2, and p53, shape and density of nucleus were relatively valuable for diagnoses. Then a diagnostic discrimination model was established. The samples were confirmed with the model, the sensitivity rates in cancer group and adenoma group were 96.36% and 89.19%, respectively. The value of proliferating cell nuclear antigen (PCNA) in early diagnosis of colorectal cancers was uncertain., Conclusion: The quantitative evaluation of some parameters for colorectal tumor can provide reproducible data for differential diagnosis. The established diagnostic discrimination model may be of clinicopathological value, and can make the early diagnosis of colorectal cancer possible.

AIM:To study the antagonism of cholecystokinin octapeptide (CCK-8) against the effect of morphine and its mechanism.METHODS:The method of simultaneously recording the electrical and mechanical activities of rat duodenum in vitro was adopted.RESULTS:Acetylcholine (ACh) could increase the amplitude and the number of the spike potential (SPA and SPN of rat duodenum in vitro, followed by the increase of the duodenal contraction amplitudes (CA), showing a positive correlation. Morphine, on the contrary, inhibited the potentiation of ACh, showing a negative correlation. CCK-8 could antagonize the effects of morphine, i.e. th SPA and SPN were increased again, followed by the increase of CA. On the basis of the above, CCK-A receptor antagonist Devazepide could reverse the antagonism of CCK-8 to the effect of morphine.CONCLUSION:CCK-8 could antagonize the effect of morphine which inhibited the potentiation of ACh on the duodenal activities in vitro.Furthermore, it was inferred that the antagonistic effect of CCK-8 on morphine was mainly mediated by CCK-A receptor.