Apoptosis In Acute Pancreatitis Research Articles

A bibliometric analysis of non-coding RNA studies in acute pancreatitis.

Non-coding RNA (ncRNA) is a type of RNA that does not code for proteins and plays a crucial role in the onset, progression, diagnosis, and therapy of acute pancreatitis. However, bibliometric, and visual analyses of studies on acute pancreatitis and ncRNA are lacking. This study seeks to provide a bibliometric overview of the knowledge structure and research hotspots of ncRNA in the field of acute pancreatitis research. Literature search and collection of information in the field of ncRNA-related research in acute pancreatitis from 2000-2023 through the Web of Science Core Collection. Use CiteSpace and VOSviewer to visually analyze countries, institutions, authors, and keywords. A total of 563 articles have been published in the field of ncRNA-related research in acute pancreatitis, and the number of publications in this field is gradually increasing. The largest number of publications was from China. Four clusters were produced by the co-occurrence cluster analysis of the top 89 keywords: studies of ncRNA in inflammation, autophagy, and apoptosis in acute pancreatitis; studies related to microRNA expression in pancreatic cancer among ncRNA; studies related to microRNAs as diagnostic and therapeutic markers in acute pancreatitis; and studies related to ncRNA in acute pancreatitis; The key words "injury," "pathway" and "extracellular vesicles" are the key words of emerging research hotspots. In conclusion, ncRNA research in acute pancreatitis is an established discipline. Researchers can use the research hotspots and frontiers in this field as a guide for choosing their research direction.

Genistein attenuated oxidative stress, inflammation, and apoptosis in L-arginine induced acute pancreatitis in mice

AimAcute pancreatitis is a common and potentially serious condition. However, a specific treatment for this condition is still lacking. Genistein, with its anti-oxidant and anti-inflammatory effects, could possibly be used to tackle the underlying pathophysiology of acute pancreatitis. Therefore, the aim of this study was to investigate the effects of genistein on oxidative stress, inflammation, and apoptosis in acute pancreatitis induced by L-arginine in mice.MethodsTwenty-four male ICR mice were equally divided into 4 groups: Control (Con); Acute pancreatitis (AP) group: Two doses of i.p. 350 mg/100 g body weight (BW) of L-arginine were administered 1 h apart; AP and low-dose genistein (LG) group: mice were given i.p. injection of 10 mg/kg genistein 2 h prior to L-arginine injection followed by once-daily dosing for 3 days; and AP and high-dose genistein (HG) group: mice were given 100 mg/kg genistein with the similar protocol as the LG group. Pancreatic tissue was evaluated for histopathological changes and acinar cell apoptosis, malondialdehyde (MDA) levels, immunohistochemical staining for myeloperoxidase (MPO), nuclear factor-kappa beta (NF-kB), and 4-hydroxynonenal (4-HNE). Serum levels of amylase (AMY), c-reactive protein (CRP), and interleukin (IL)-6 were measured.ResultsSignificant increases in the degree of acinar cell apoptosis, pancreatic MDA, serum IL-6 and amylase, MPO, NF-kB and 4-HNE positivity were observed in the AP group. All these parameters declined after low- and high-dose genistein treatment. Severe pancreatic inflammation, edema, and acinar cell necrosis were observed in the AP group. Significant improvement of histopathological changes was seen in both low- and high-dose genistein groups. There were no significant differences in any parameters between low and high doses of genistein.ConclusionGenistein could attenuate the severity of histopathological changes in acute pancreatitis through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.

MiR-489-3p modulates cell proliferation and apoptosis in cerulein-induced acute pancreatitis by targeting X-linked inhibitor of apoptosis protein

IntroductionThis study aims to explore the effect and mechanism of miR�489-3p on the proliferation and apoptosis of pancreatic acinar cells in acute pancreatitis (AP).Material and methodsX-linked inhibitor of apoptosis protein (XIAP) and miR-489-3p expression in serum of AP patients, pancreatic AR42J cells, and rat AP tissues were measured using quantitative reverse transcription poly�merase chain reaction and western blot. The effect of miR-489-3p on pro�liferation and apoptosis was determined by MTT assay and flow cytometry. The relationship between XIAP and miR-489-3p was verified using luciferase assay RNA immunoprecipitation assay. Histological changes in rat pancreatic tissues were observed via haematoxylin and eosin staining.ResultsMeasurement of miR-489-3p and XIAP expressions in AP patients revealed a negative correlation between miR-489-3p and XIAP. Increased miR-489-3p expression in AP patients indicated a poor prognosis. Cerulein was used to induce AP in AR42J cells and standard deviation rats. Exper�iments in cells and AP rat models showed that miR-489-3p can increase cell apoptosis and inhibit cell proliferation by regulating XIAP, as shown by elevated expressions of pro-apoptotic proteins (p53 and Bax) and decreased expression of proliferation indicator (Ki-67) after transfection of miR-489- 3p mimics. Meanwhile, knockdown of miR-489-3p abrogated the inhibitory effects of miR-489-3p on cell proliferation and the promotion on cell apop�tosis. Luciferase assay and RNA immunoprecipitation assay confirmed that XIAP can directly bind miR-489-3p.ConclusionsWe concluded that miR-489-3p modulates cell proliferation and apoptosis in AP by targeting XIAP. Given that high expression of miR�489-3p in AP indicated poor prognosis, it raises the possibility that miR�489-3p might be a novel and valuable therapeutic target and a prognosis indicator for AP.

SAT-684 A Deadly Triad: Coexistence of Acute Pancreatitis, Hypertryglyceridemia and Diabetic Ketoacidosis

The coexistence of diabetic ketoacidosis (DKA), hypertriglyceridemia and acute pancreatitis (AP) represent a complex phenomenon described as the enigmatic triad. The exact initial culprit and pathophysiologic mechanism of this chain of events are still unclear posing a challenge in management. DKA may lead to glucose and lipid metabolism dysregulation which can result in hypertriglyceridemia leading to AP. On the other hand, hypertriglyceridemia may induce AP which may decompensate diabetes and lead to DKA. In both scenarios, this triad results in an uncommon clinical presentation with up to 80% mortality rate. Most frequently reported in children, this entity accounts for only a handful of cases reported in the literature.Case of an obese, non alcoholic 57 year old male without history of systemic illness who visits the emergency room due to mid-upper abdominal pain for the past day. Pain radiates to the back, worsens upon laying flat, and is associated with bloating and nausea. He denies previous similar episodes, vomiting, fever or bowel habit changes. Laboratory workup revealed lipidemic sample with hyperglycemia, metabolic acidosis, positive serum ketones, and normal amylase and lipase. Lipid panel revealed hypertriglyceridemia at 6,260 mg/dL (35-150). Glycated hemoglobin at 14.7%. Abdominal computed tomography showed peripancreatic inflammation consistent with pancreatitis. Given clinical and imaging criteria the diagnosis of severe hypertriglyceridemia induced AP and DKA were made. The patient was admitted to ICU and treated with intravenous insulin drip and supportive management. Resolution of DKA and successful decrease in triglycerides to less than 500 mg/dL was achieved by the third day of admission. After six days, the patient was discharged home with insulin and lipid lowering regimens.This case demonstrates an extremely rare initial presentation of diabetes mellitus. This triad is the result of a toxic chain of events that may be lethal if not promptly identified. This case makes an exemplary lesson as to always take under consideration atypical etiologies to potentially life threatening conditions and also remarks that while uncommon, pancreatitis with normal pancreatic enzymes is a possible phenomenon. Even though false negative amylase has been associated with hypertriglyceridemia induced AP, only a few cases with negative lipase have been described. While no definite explanation has been yet discovered, negative lipase may be explained by early acinar cell apoptosis in AP. More research efforts are necessary in order to improve early diagnosis, treatment, and mortality rate for this rare but potentially deadly triad and to better understand the mechanisms underlying AP and the role that digestive enzymes play.

The lysosomal protease Cathepsin C regulates leukocyte invasion and apoptosis in acute pancreatitis

The lysosomal protease Cathepsin C regulates leukocyte invasion and apoptosis in acute pancreatitis

Endoplasmic reticulum stress may not be involved in intestinal epithelial cell apoptosis in experimental acute pancreatitis.

To investigate whether endoplasmic reticulum (ER) stress is activated in the intestinal epithelium of acute pancreatitis (AP), and whether it is one of the inducing factors of the intestinal epithelial cell apoptosis in AP. Twenty-four rats were randomly divided into two groups. AP was induced via retrograde injection of 3 % sodium taurocholate into the pancreatic duct. As a control group, rats received a sham operation. Forty-eight hours after the operation, the ultrastructural changes of ileal epithelial cells were investigated by transmission electron microscope. The protein expressions of GRP78, CHOP, caspase-12, and JNK in the ileal epithelium were determined by immunohistochemistry, and apoptosis was determined by TdT-mediated dUTP nick end labeling. The mRNA expressions of GRP78, CHOP, caspase-12, and JNK in the ileal epithelium were determined using quantitative RT-PCR. The ileal epithelium in rats with AP had significantly higher apoptotic cells compared with that of the control rats (P < 0.05). ER stress was activated in the ileal epithelium, which was characterized by dilated, irregular ER and upregulated expressions of GRP78 mRNA and protein. The mRNA and protein expressions of CHOP, caspase-12, and JNK in rats with AP were similar to that in the control rats (P > 0.05). ER stress is induced in intestinal epithelium during AP; however, ER stress is not likely to be involved in the apoptosis of the intestinal epithelium during AP.

P8 Deficiency causes siderosis in spleens and lymphocyte apoptosis in acute pancreatitis.

The gene p8 was initially described in pancreatic tissue during acute experimental pancreatitis, a disease that is characterized by a systemic immune response. Although early reports suggested that p8 affects leukocyte migration during acute pancreatitis (AP), no studies revealing its immune-modulatory effects have been performed. We investigated the composition of the cellular immune system in naive p8 knockout (p8(−/−)) mice and compared with matched wild-type mice during pancreatitis. In young mice, there were no relevant differences in the composition of peripheral and splenic CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD11b(+)Gr-1(-), and Gr-1 cells. In mature p8(−/−) mice, increased splenic CD4CD25FoxP3 cells, spleen siderosis, and increased marginal zones in the splenic white pulp were found. During AP, peripheral and splenic CD3(+) and CD3CD4 declined stronger in the p8(−/−) mice. The spleen of the p8(−/−) mice showed severe hypoplasia of the white pulp and mild hyperplasia of the red pulp. This was associated with a significantly increased rate of apoptosis. We conclude that p8 has no impact on the cellular composition of the adaptive and innate immune systems in noninflammatory conditions. However, it may limit apoptosis and maintain homeostasis of the immune reaction during AP.

Change of T lymphocyte subsets and their different apoptosis in acute pancreatitis

Objective To investigate the dynamic change and different apoptosis of T lymphocyte subsets in patients with acute pancreatitis.Methods Forty-four patients with MAP and 32 with SAP were enrolled in this study.Blood samples were collected on the lst,3rd and 7th d after onset.T lymphocyte subsets and their apoptotic rate were determined by flow cytometry.Results Compared with the control group and MAP group,CD4+ T lymphocytes and the ratio of CD4+/CD8+remarkably decreased while the apoptotic rate of CD4+ T cells significantly increased in patients with SAP.However,there was no marked difference in apoptotic rate of CD8+ T cells among different groups.Conclusion The different apoptosis of T lymphocyte subsets in AP,especially in SAP,results in severe and sustained cellular immune suppression. Key words: Pancreatitis; T lymphocyte subset; Apoptosis; Immune function

Induction of Apoptosis by Crambene Protects Mice against Acute Pancreatitis via Anti-Inflammatory Pathways

Apoptosis is a teleologically beneficial form of cell death in acute pancreatitis. Our previous work has demonstrated that induction of pancreatic acinar cell apoptosis by crambene protects mice against acute pancreatitis. However, little is known about how the induction of apoptosis reduces the severity of acute pancreatitis. Because the clearance of apoptotic cells might suppress inflammation and critically regulate immune responses, we postulate that clearance of apoptotic cells stimulates an anti-inflammatory response, which has a protective action against acute pancreatitis. To test this hypothesis, induction of apoptosis in acute pancreatitis in vivo and co-cultures of peritoneal resident macrophages with apoptotic acinar cells in vitro were used as experimental systems, testing expression of phagocytic receptors and levels of inflammatory mediators. Moreover, neutralizing anti-interleukin (IL)-10 monoclonal antibody (2.5 mg/kg) was used before the induction of apoptosis in acute pancreatitis, testing whether the protection from apoptosis induction would be removed. Our study showed that clearance of apoptotic acinar cells, which may occur essentially through the CD36-positive macrophage, stimulates the release of anti-inflammatory mediators like IL-10. IL-10 plays an important role in crambene-induced protection in acute pancreatitis. Thus, induction of pancreatic acinar cell apoptosis by crambene protects mice against acute pancreatitis via induction of anti-inflammatory pathways.

Progress of Study on the Relationship Between Mediators of Inflammation and Apoptosis in Acute Pancreatitis

As an important pathological feature of acute pancreatitis, apoptosis may occur in multiple organs and relate directly to the progression of disease. It is mainly controlled by the apoptosis gene and also influenced by inflammatory mediators. We summarize here the roles of the main inflammatory mediators (e.g., NO, TNF-alpha, TGF-beta1, IL-10, NF-kappaB) during the pathologic process of acute pancreatitis.

Altered caspase expression results in delayed neutrophil apoptosis in acute pancreatitis

Acute pancreatitis (AP) may lead to the development of multiple organ dysfunction syndrome (MODS), especially in severe cases. Resolution of such inflammatory responses is dependent on neutrophil apoptosis. Delays in this apoptotic response are associated with persistent inflammation and subsequent tissue damage. The aim of this study is to determine the effects of AP on neutrophil apoptosis and to investigate the underlying mechanisms involved. Neutrophils and serum were isolated from control (n=10) and from patients with AP (mild, n=35, and severe, n=5). Neutrophil apoptosis was assessed by propidium iodide DNA staining using flow cytometry. Caspase, glutathione-S-transferase (GST), and Mcl-1 protein expression were assessed by SDS-PAGE western blotting. Serum interleukin (IL)-1beta and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were measured by ELISA. Neutrophils isolated from patients with AP show a significant delay in spontaneous neutrophil apoptosis. Serum factors contributed to this delay with increases in IL-1beta and GM-CSF. Isolated neutrophils were resistant to Fas antibody-induced apoptosis. Caspases represent a central mechanism for spontaneous and Fas antibody-induced neutrophil apoptosis. Procaspase 3 expression was decreased in mild and severe cases, but this effect was independent of serum factors. Increases in GST expression may also contribute to the antiapoptotic effect. Altered caspase expression may represent an additional factor contributing to delayed neutrophil apoptosis. This may contribute to the development of AP and its related complications.