The Effects of Umbilical Cord Mesenchymal Stem Cells on Traumatic Pancreatitis in Rats.

OBJECTIVE: This study explored the therapeutic and protective effects of umbilical cord mesenchymal stem cells (ucMSCs) on traumatic pancreatitis (TP) to provide a theoretical basis for TP treatment with MCSs by establishing a TP rat model. METHODS: We used 60 healthy adult male Sprague Dawley (SD) rats to create four experimental groups: sham, ucMSC control, TP, and ucMSC treatment. We observed ucMSC homing in the rats by fluorescence microscopy and assessed the degree of pancreatic tissue injury by hematoxylin and eosin (HE) staining on days 1, 3, and 7 after transplantation. Furthermore, we used an in vivo imaging system to evaluate the localization of cell membrane-stained ucMSCs in rats with TP. Finally, we measured the serum levels of amylase, lipase, pro-and anti-inflammatory factors, and oxidative stress factors by enzyme-linked immunosorbent assay (ELISA). RESULTS: The pancreatic histopathological score and the serum amylase and lipase levels were lower in the ucMSC treatment group than in the TP group (P < 0.05). Interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and oxidase malondialdehyde (MOD) levels were significantly higher in the ucMSC treatment group than in the TP group. However, IL-10, transforming growth factor-ß, and superoxide dismutase (an antioxidant enzyme, SOD) levels were significantly higher in the ucMSC treatment group than in the TP group (P < 0.05). CONCLUSION: ucMSCs can migrate and implant in injured areas of the pancreas in rats. Furthermore, they participate in pancreatic tissue repair and regulate immunity by inhibiting the systemic inflammatory response and oxidative stress.

Enhancing or inhibiting apoptosis? The effects of ucMSC-Ex in the treatment of different degrees of traumatic pancreatitis.

The animal models of traumatic pancreatitis (TP) were established to evaluate the specific mechanisms by which umbilical cord mesenchymal stem cell-derived exosomes (ucMSC-Ex) exert therapeutic effects. Sixty four rats were randomly divided into eight groups, including TP groups with three different degrees and relevant groups with ucMSC-Ex treated. The degrees of pancreatic tissue injury were evaluated by Histological Examination. Furthermore, enzyme-linked immunosorbent assay were applied to evaluate the activity of pancreatic enzymes and levels of inflammatory factors in serum. Finally, the apoptotic effects of each group were evaluated by TUNEL, western blot (WB), and real time fluorescence quantitative polymerase chain reaction (RT-qPCR). The pancreatic histopathological score and serum amylase and lipase levels gradually increased in various degrees of TP and the levels in the treatment group were all significantly decreased. The apoptosis index gradually increased in each TP group and significantly decreased in the treatment group in TUNEL results. WB and RT-qPCR showed the same trend, that bax and caspase-3 gradually increased and bcl-2 gradually decreased in TP groups. Compared with TP groups, the expression of bax and caspase-3 were lower while bcl-2 expression was higher in the treatment group. ucMSC-Ex suppressed the inflammatory response and inhibited pancreatic acinar cell apoptosis to promote repair of injured pancreatic tissue.

Methionine selenium antagonizes LPS-induced necroptosis in the chicken liver via the miR-155/TRAF3/MAPK axis.

Organic selenium has antioxidation and disease treatment effects. To explore the mechanisms of how methionine selenium alleviates necroptosis in the liver and whether this process is related to microRNA (miRNA) and the mitogen-activated protein kinase (MAPK) pathway, an animal model of methionine selenium and the lipopolysaccharide (LPS) interaction was established. The morphology, inflammatory factor (tumor necrosis factor-α [TNF-α]), necroptosis-related genes (RIP1, RIP3, MLKL, and caspase 8), MAPK pathway-related genes (JNK, ERK, and p38, p-JNK, p-ERK, and p-p38), gga-miR-155, TRAF3 (predicted target of gga-miR-155), and oxidative stress-related indicators (SOD, MDA, CAT, GSH, and GSH-Px) were analyzed from the perspective of the miR-155/TRAF3/MAPK axis to elucidate the mechanism of methionine selenium on the LPS-induced necroptosis mechanism in the chicken liver. The current results suggested that methionine selenium antagonizes oxidative stress, inflammation, and the MAPK pathway, thereby antagonizing the occurrence of necroptosis through multiple mechanisms. At the same time, methionine selenium affects miR-155/TRAF3/MAPK signaling, reduces miR-155 expression, and upregulates TRAF3 expression to inhibit necroptosis. This information provided new ideas and a theoretical basis for the practical application of methionine selenium, and it also enriched the study of miRNAs in birds and provided a reference for comparative medicine.

Establishment of a multifunctional impact system and a study of a pancreatic trauma model in rats based on controlling the injury area.

Background: At present, basic scientific research on pancreatic trauma is rare due to the lack of ideal animal models and modeling equipment for pancreatic trauma. Therefore, we intend to develop a multifunctional impact system with simple operation, diverse impact and accurate measurement and to establish a rat pancreatic trauma model based on injury area control by using the system. Methods: The impactor was designed based on the convenience of the impact energy acquisition, the diversity of the impact operation, and the precision of the impact strength parameter measurement by the team. The efficacy and stability/repeatability of the impactor were preliminarily evaluated. An impact head with different impact areas (3 cm2 and 6 cm2) of the impactor was used to squeeze the rat pancreas in the abdomen to form different injury areas under a pressure of 400 kPa. The efficacy features of this trauma model were evaluated by detecting the outcomes of pathology and biochemistry at 24 h after injury in the two groups. Furthermore, these changes were also evaluated at 6 h, 24 h, 48 h and 72 h after injury in the 3 cm2 trauma group. Result: Multifunctional impactors were successfully explored. The impact force was continuously adjustable with a range of 0-200 kg. The compression and extrusion stress ranges were continuously adjustable from 0 to 100 kg. System adjustment verified that the impactor had fine efficacy (P < 0.05) and stability/repeatability (P > 0.05). Compared with the control group, rats in the pancreatic trauma group with different injury areas exhibited obvious injuries (P < 0.05), and compared with the 3 cm2 trauma group, the 6 cm2 trauma group exhibited the more severe injury (P < 0.05). After modeling, the injury characteristics at different time points showed stable differences(P < 0.05). Conclusions: A rat pancreatic trauma model based on injury area control was successfully established using the impactor developed in this study. This model is simple, effective, controllable, and suitable for animal experimental research on pancreatic trauma.

Ferroptosis in pancreatic diseases: potential opportunities and challenges that require attention.

The pancreas is an abdominal organ with both endocrine and exocrine functions, and patients with pancreatic diseases suffer tremendously. The regulated cell death of various cells in the pancreas is thought to play a key role in disease development. As one of the newly discovered regulated cell death modalities, ferroptosis has the potential for therapeutic applications in the study of multiple diseases. Ferroptosis has been observed in several pancreatic diseases, but its role in pancreatic diseases has not been systematically elucidated or reviewed. Understanding the occurrence of ferroptosis in various pancreatic diseases after damage to the different cell types is crucial in determining disease progression, evaluating targeted therapies, and predicting disease prognosis. Herein, we summarize the research progress associated with ferroptosis in four common pancreatic diseases, namely acute pancreatitis, chronic pancreatitis, pancreatic ductal adenocarcinoma, and diabetes mellitus. Furthermore, the elucidation of ferroptosis in rare pancreatic diseases may provide sociological benefits in the future.