St13 protects against disordered acinar cell arachidonic acid pathway in chronic pancreatitis.

BACKGROUND: Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP. METHODS: Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13-/- mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model. RESULTS: The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling. CONCLUSION: St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.

EMC6 regulates acinar apoptosis via APAF1 in acute and chronic pancreatitis.

Treatment of acute pancreatitis (AP) and chronic pancreatitis (CP) remains problematic due to a lack of knowledge about disease-specific regulatory targets and mechanisms. The purpose of this study was to screen proteins related to endoplasmic reticulum (ER) stress and apoptosis pathways that may play a role in pancreatitis. Human pancreatic tissues including AP, CP, and healthy volunteers were collected during surgery. Humanized PRSS1 (protease serine 1) transgenic (PRSS1Tg) mice were constructed and treated with caerulein to mimic the development of human AP and CP. Potential regulatory proteins in pancreatitis were identified by proteomic screen using pancreatic tissues of PRSS1Tg AP mice. Adenoviral shRNA-mediated knockdown of identified proteins, followed by functional assays was performed to validate their roles. Functional analyses included transmission electron microscopy for ultrastructural analysis; qRT-PCR, western blotting, co-immunoprecipitation, immunohistochemistry, and immunofluorescence for assessment of gene or protein expression, and TUNEL assays for assessment of acinar cell apoptosis. Humanized PRSS1Tg mice could mimic the development of human pancreatic inflammatory diseases. EMC6 and APAF1 were identified as potential regulatory molecules in AP and CP models by proteomic analysis. Both EMC6 and APAF1 regulated apoptosis and inflammatory injury in pancreatic inflammatory diseases. Moreover, APAF1 was regulated by EMC6, induced apoptosis to injure acinar cells and promoted inflammation. In the progression of pancreatitis, EMC6 was activated and then upregulated APAF1 to induce acinar cell apoptosis and inflammatory injury. These findings suggest that EMC6 may be a new therapeutic target for the treatment of pancreatic inflammatory diseases.

ATF6 aggravates acinar cell apoptosis and injury by regulating p53/AIFM2 transcription in Severe Acute Pancreatitis.

Background: There is no curative therapy for severe acute pancreatitis (SAP) due to poor understanding of its molecular mechanisms. Endoplasmic reticulum (ER) stress is involved in SAP and increased expression of ATF6 has been detected in SAP patients. Here, we aimed to investigate the role of ATF6 in a preclinical SAP mouse model and characterize its regulatory mechanism. Methods: Pancreatic tissues of healthy and SAP patients were collected during surgery. Humanized PRSS1 transgenic mice were treated with caerulein to mimic the SAP development, which was crossed to an ATF6 knockout mouse line, and pancreatic tissues from the resulting pups were screened by proteomics. Adenovirus-mediated delivery to the pancreas of SAP mice was used for shRNA-based knockdown or overexpression. The potential functions and mechanisms of ATF6 were clarified by immunofluorescence, immunoelectron microscopy, Western blotting, qRT-PCR, ChIP-qPCR and luciferase reporter assay. Results: Increased expression of ATF6 was associated with elevated apoptosis, ER and mitochondrial disorder in pancreatic tissues from SAP patients and PRSS1 mice. Knockout of ATF6 in SAP mice attenuated acinar injury, apoptosis and ER disorder. AIFM2, known as a p53 target gene, was identified as a downstream regulatory partner of ATF6, whose expression was increased in SAP. Functionally, AIFM2 could reestablish the pathological disorder in SAP tissues in the absence of ATF6. p53 expression was also increased in SAP mice, which was downregulated by ATF6 knockout. p53 knockout significantly suppressed acinar apoptosis and injury in SAP model. Mechanistically, ATF6 promoted AIFM2 transcription by binding to p53 and AIFM2 promoters. Conclusion: These results reveal that ATF6/p53/AIFM2 pathway plays a critical role in acinar apoptosis during SAP progression, highlighting novel therapeutic target molecules for SAP.

Risk factors for the concomitant occurrence of alcoholic chronic pancreatitis and alcoholic liver cirrhosis: a 10-years cohort study at a tertiary hospital in China.

OBJECTIVE: Concomitant occurrence of alcoholic chronic pancreatitis (ACP) and alcoholic liver cirrhosis (ALC) is rare with few reported cases. The present study aimed to identify the potential risk factors of chronic pancreatitis (CP) and liver cirrhosis (LC) in ALC patients and ACP patients, respectively. METHODS: A retrospective analysis was performed on 536 patients with CP and 647 ALC patients without CP (Group A). Among the 536 CP patients, 213 ACP cases were divided into two groups: ACP with LC (Group B, n = 52) and ACP without LC (Group C, n = 161). A comparison between Group A and B was carried out to identify the potential risk factors of CP in ALC patients, while Group B and C were compared to determine the independent risk factors of LC in ACP patients. RESULTS: Concomitant occurrence of ACP and ALC accounted for 24.4% (52/213) in this cohort. Significant risk factors for CP in ALC patients included smoking [odds ratio (OR), 2.557; 95% confidence interval (CI): 1.531-5.489; P = 0.003] and multiple bouts of acute pancreatitis (OR, 4.813; 95% CI: 3.625-12.971; P < 0.001). Hepatitis B virus (HBV) infection (OR, 4.237; 95% CI: 1.742-7.629; P = 0.012) was the only independent risk factor associated with LC in ACP patients. CONCLUSION: HBV infection exacerbated liver damage in ACP patients. Alcoholic patients who smoked and suffered from ongoing bouts of acute pancreatitis are prone to develop CP.

Anatomy and three-dimensional reconstruction study of SSL area / 中国实用妇科与产科杂志

OBJECTIVE: Use cadavers and three-dimensional MRA models to study the anatomical relationship between the sacrospinous ligament(SSL)and its adjacent vessels and nerves.METHODS: Totally 24 female cadavers provided by Anatomy Department of Southern Medical University from September 2017 to September 2018 were dissected,and 30 MRA data collected by Gynecology Department of Nanfang Hospital of Southern Medical University from January 2015 to December 2018 were selected to reconstruct to measure the relevant application parameters.RESULTS: The medial structure of the pudendal canal was the pudendal nerve,and the horizontal distance between the right pudendal nerve and the sciatic spine was(1.51 ± 0.35)cm. The thickness of the thickest point of the right coccygeus-sacrospinousligament(CSSL)was(1.03±0.23)cm and the horizontal distance between the point and the right sciatic spine was(2.81±0.55)cm;the vertical distance from where the right inferior gluteal artery is out of pelvis cavity to the horizontal line of sciatic spine was(2.43±0.95)cm,and the distance between the vertical point and the sciatic spine was(1.83±0.83)cm. In anatomy and MRA model,none of the inferior gluteal artery went dorsally through the SSL,and the sciatic nerve was away from the SSL.There was no obvious vascular nerve traveling on the pelvic surface of SSL.CONCLUSION: The point which is 2.81 cm away from the right sciatic spine of the SSL at the horizonal level may be the best suspension point for SSLF.

Recent progress in study on anti-oxidant activity of endophytes in medicinal plants / 中草药

Endophyte is a significant biological resource which exists in plant cells without any negative effects for plants. After a long period of evolution, endophyte and its host plants keep a relatively stable symbiosis by producing some special active ingredients. Therefore, plant endophyte is the essential source of active ingredients and leading compound, while antioxidants attract the most attention of all ingredients. There is abundant diversity of antioxidant activity endophytes in medicinal plants, especially endophytic fungi and endophytic actinomyces. Here we summarize the recent research progress in the antioxidant activity endophytes from the relationship between the antioxidant activity endophytes and host plants, their ecological significance, diversity of antioxidant activity endophytes, and active ingredients. And the future research and development direction of this field is prospected.

Comparative analysis of biological characteristics of adult mesenchymal stem cells with different tissue origins

Objective: To invest the differences among mesenchymal stem cells (MSCs) derived from different tissues and their impacts on clinical applications. Methods: In this study, MSCs were isolated from adipose tissue (AD), umbilical cord tissue (UC), and menstrual blood (Men) and compared their biological characteristics in terms of proliferation capacity, passage capacity, colony formation, and surface markers were compared. Results: The stem cells (SCs) obtained from different sources were all characterized as MSCs, but demonstrated some differences. Umbilical cord-derived MSCs (UCMSCs) were able to overcome density inhibition. The proliferation rate decreased in the order UCMSCs > MenSCs > ADSCs, while the colony-forming ability decreased in the order MenSCs > ADSCs > UCMSCs. Based on gene-expression data for MSCs from different sources within the same donor, 768 MenSC genes were found that were specifically upregulated or downregulated compared with bone marrow-derived MSCs and UCMSCs, most of which were involved in cell function-related pathways. In addition, MenSCs appeared to be superior in terms of immune inflammation, stress response, and neural differentiation potentials, but weaker in terms of osteogenic and chondrogenic differentiation capacities, compared with UCMSCs and bone marrow-derived MSCs. Conclusions: MenSCs have higher extraction efficiency, colony-forming ability, and long time passage capacity. Although the proliferation capacity is inferior to UCMSCs.

Comparative analysis of biological characteristics of adult mesenchymal stem cells with different tissue origins

OBJECTIVE@#To invest the differences among mesenchymal stem cells (MSCs) derived from different tissues and their impacts on clinical applications.@*METHODS@#In this study, MSCs were isolated from adipose tissue (AD), umbilical cord tissue (UC), and menstrual blood (Men) and compared their biological characteristics in terms of proliferation capacity, passage capacity, colony formation, and surface markers were compared.@*RESULTS@#The stem cells (SCs) obtained from different sources were all characterized as MSCs, but demonstrated some differences. Umbilical cord-derived MSCs (UCMSCs) were able to overcome density inhibition. The proliferation rate decreased in the order UCMSCs > MenSCs > ADSCs, while the colony-forming ability decreased in the order MenSCs > ADSCs > UCMSCs. Based on gene-expression data for MSCs from different sources within the same donor, 768 MenSC genes were found that were specifically upregulated or downregulated compared with bone marrow-derived MSCs and UCMSCs, most of which were involved in cell function-related pathways. In addition, MenSCs appeared to be superior in terms of immune inflammation, stress response, and neural differentiation potentials, but weaker in terms of osteogenic and chondrogenic differentiation capacities, compared with UCMSCs and bone marrow-derived MSCs.@*CONCLUSIONS@#MenSCs have higher extraction efficiency, colony-forming ability, and long time passage capacity. Although the proliferation capacity is inferior to UCMSCs.