1.Adipose stem cells regulate the CHOP/Bcl-2 pathway to alleviate acute pancreatic injury in dogs
Mingzhen CHEN ; Ruxin DING ; Zhiying WAN ; Yansong GE ; Jiasan ZHENG
Chinese Journal of Veterinary Science 2025;45(11):2500-2506
Acute pancreatitis(AP)is a common and severe digestive disease in dogs,characterized by a high recurrence rate and complications that significantly impact canine health.This study in-vestigates the mechanism by which adipose-derived stem cells(ADSCs)regulate the CHOP/Bcl-2 pathway to mitigate acute pancreatic injury in dogs.Twenty Beagle dogs were randomly divided in-to four groups:a Sham group,an AP model group,an ADSCs treatment group,and a conditioned medium(CM)treatment group.The AP model was established by injecting a mixed solution of trypsin and sodium taurocholate into the AP model group.The ADSCs treatment group received intravenous injections of ADSCs immediately following surgery,while the CM treatment group re-ceived conditioned medium preparations.Pancreatic tissue was collected 24 hours post-surgery,and changes in the CHOP/Bcl-2 pathway were assessed using histopathology,transmission electron microscopy,western blotting,fluorescence quantification,immunofluorescence,and TUNEL stai-ning.The results indicated that AP induced significant interstitial edema,hemorrhage,inflammato-ry cell infiltration,chromatin contraction,and endoplasmic reticulum swelling,the expression lev-els of GRP78 and CHOP were found to be elevated,whereas the expression of Bcl-2 was downreg-ulated.Additionally,the expression levels of BAX,JNK,Caspase-3,and Caspase-12 increased,leading to an increased rate of cell apoptosis.Such changes result in an elevated apoptosis rate and a further decrease in Bcl-2 expression.Both ADSCs and CM therapy were found to alleviate the path-ological damage in pancreatic tissue,resulting in downregulation of CHOP and apoptosis-related markers,upregulation of Bcl-2,and a reduction in the apoptosis rate.The results of this study sug-gest that ADSCs may mitigate acute pancreatic injury induced by trypsin and sodium taurocholate in AP dogs by modulating the CHOP/Bcl-2 pathway.Targeted modulation of the transcriptional activity of CHOP may offer novel therapeutic approaches for AP.
2.Adipose stem cells regulate the CHOP/Bcl-2 pathway to alleviate acute pancreatic injury in dogs
Mingzhen CHEN ; Ruxin DING ; Zhiying WAN ; Yansong GE ; Jiasan ZHENG
Chinese Journal of Veterinary Science 2025;45(11):2500-2506
Acute pancreatitis(AP)is a common and severe digestive disease in dogs,characterized by a high recurrence rate and complications that significantly impact canine health.This study in-vestigates the mechanism by which adipose-derived stem cells(ADSCs)regulate the CHOP/Bcl-2 pathway to mitigate acute pancreatic injury in dogs.Twenty Beagle dogs were randomly divided in-to four groups:a Sham group,an AP model group,an ADSCs treatment group,and a conditioned medium(CM)treatment group.The AP model was established by injecting a mixed solution of trypsin and sodium taurocholate into the AP model group.The ADSCs treatment group received intravenous injections of ADSCs immediately following surgery,while the CM treatment group re-ceived conditioned medium preparations.Pancreatic tissue was collected 24 hours post-surgery,and changes in the CHOP/Bcl-2 pathway were assessed using histopathology,transmission electron microscopy,western blotting,fluorescence quantification,immunofluorescence,and TUNEL stai-ning.The results indicated that AP induced significant interstitial edema,hemorrhage,inflammato-ry cell infiltration,chromatin contraction,and endoplasmic reticulum swelling,the expression lev-els of GRP78 and CHOP were found to be elevated,whereas the expression of Bcl-2 was downreg-ulated.Additionally,the expression levels of BAX,JNK,Caspase-3,and Caspase-12 increased,leading to an increased rate of cell apoptosis.Such changes result in an elevated apoptosis rate and a further decrease in Bcl-2 expression.Both ADSCs and CM therapy were found to alleviate the path-ological damage in pancreatic tissue,resulting in downregulation of CHOP and apoptosis-related markers,upregulation of Bcl-2,and a reduction in the apoptosis rate.The results of this study sug-gest that ADSCs may mitigate acute pancreatic injury induced by trypsin and sodium taurocholate in AP dogs by modulating the CHOP/Bcl-2 pathway.Targeted modulation of the transcriptional activity of CHOP may offer novel therapeutic approaches for AP.
3.Change of serum metalloproteinases and metalloproteinases inhibitors in exfoliation syndrome in Uyghur population
Yan, TANG ; Ruxin, DING ; Tingyu, XIE ; Xueyi, CHEN
Chinese Journal of Experimental Ophthalmology 2014;32(7):631-634
Background Exfoliation syndrome is a systemic disease with abnormal accumulation of extracellular matrix.Oxidative stress and imbalance between matrix metalloproteinases(MMPs) and tissue inhibitor of matrix metalloproteinases(TIMPs)may play an important role in the pathogenesis of exfoliation syndrome.Researches showed that the incidence of exfoliation syndrome is higher in Uyghur nationality than that in Han nationality.However,whether the imbalance of serum MMPs and TIMPs is associated with pathogenesis of different ethnic groups is unclear.Objective The aim of the study was to discuss the change of serum MMP-9 and TIMP-2 in Uyghur patients.Methods This study protocol was approved by Ethic Committee of Xinjiang Medical University and followed Declaration of Helsinki.A prospective cohort study was performed.Forty Uyghur nationality (46 eyes) with exfoliation syndrome were collected from March 2012 to May 2013 in Affiliated First Hospital of Xinjiang Medical University and First People Hospital of Kashi.Forty cases(40 eyes)age-and gender-matched normal volunteers were included in the same duration.The peripheral blood was collected under the informed consent.Serum MMP-9 and TIMP-2 levels were detected by ELISA,and the results between the two groups were compared using independent samples t test.Results Slit-lamp examination found that part of pigmentation was depigmented and white dandrufflike substance attached in the pupil margin in all the patients,and stripping white dandruff-like substance was deposited in the front surface of the lens capsule which distributed in 3 zones.The pupils were disk-shaped pupil,and the surrounding area was the ring granular and the middle was transparent area without ablative material after dilation.Serum MMP-9 levels were (57.88±18.63)μg/L in the exfoliation syndrome group and (9.35±2.78)μg/L in the normal control group;serum TIMP-2 levels were (17.36±4.66) μg/L in the exfoliation syndrome group and (25.73±3.59) μg/L in the control group.The ratios of MMP-9/TIMP-2 were 3.57± 1.45 in the exfoliation syndrome group and 0.37±0.11 in the control group,with statistically significant differences in serum MMP-9 and TIMP-2 levels as well as ratio of MMP-9/TIMP-2 between the two groups(t=11.52,-6.36,9.87,all at P=0.00).Conclusions The upregulation of serum MMP-9 and downregulation of serum TIMP-2 are found in Uyghur patients with exfoliation syndrome.It is verified that the imbalance of serum MMP-9 and TIMP-2 contributes to the pathogenesis of exfoliation syndrome in Uyghur patients.

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