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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Custom-Made Endograft for Endovascular Repair of Thoraco-Abdominal Aneurysm and Type B Dissection: Single-Centre Experience

AimsTo report a series of patients treated with the Jotec custom-made endograft for thoraco-abdominal aneurysms and dissections and identify predictive factors for re-intervention.MethodsWe retrospectively analysed 49 patients unsuitable for surgery, treated between 2011 and 2017 (71.3 ± 9.5 years; 15 females). Indications included Crawford type 4 aneurysm in 25 patients, type 3 in 13, type 2 in 4, type 1 in 2 and chronic aneurysmal dilatation of the false lumen following dissection in 5 cases. Mean aneurysm diameter was 58.7 ± 8.4 mm. The study aims were to assess procedural success, complications rate, mortality and long-term follow-up. We also analysed factors that predicted the need for re-intervention.ResultsThe endograft was successfully deployed in all patients, catheterization of the fenestration and/or branches was achieved in 152/156 (97.4%) vessels. Early complications occurred in 10 patients (3 paraplegia, 3 haemorrhages, pancreatitis, aortic rupture, iliac artery rupture, 2 strokes). Thirty-day mortality was 10.2% and 180-day mortality 14.3%; two non procedure related deaths occurred. Mean follow-up was 23.6 ± 29.9 months [range 1–80]. No patients needed surgical explantation or developed significant renal impairment. Endoleak rate was 34.6% and re-intervention rate 9.7%. The aneurysm sac reduced or was stable in 36/49, and enlarged in 9/49 patients prompting re-intervention. Primary, primary-assisted and secondary patency of fenestrations/branches at 80 months was 90, 96 and 100%. Re-intervention was required more frequently in braches than in fenestrations, most commonly the external type branches.ConclusionsThe results of the Jotec endograft are comparable to other devices, with acceptable complication and re-intervention rates. Fenestration and inner-branch should be preferred due to lower re-intervention rates.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Which G-Tube to Use in Pullers: Assessment of Pull Pressures on Skin Models to Determine Optimal Catheter Choice in Patients with Recurrent Pulled Gastrostomy Tubes

Introduction: Pulled or dislodged gastrostomy catheters represent a common complication associated with percutaneous gastrostomy and are a common cause of recurrent visits in patients with altered mental status. We intended to perform an experiment to compare the pull forces required to dislodge different commonly used gastrostomy catheters. Materials and Methods: We used a digital force gauge device to measure the pull forces required to dislodge three types of 20 French gastrostomy catheters in double-layer skin models. These included the Flow 20 Pull Method (Cook Medical, Bloomington, IN, USA), Entuit Gastrostomy BR Balloon Retention feeding tube (Cook Medical, Bloomington, IN, USA), and Ponsky Non-Balloon Replacement Gastrostomy Tube (CR Bard Inc, Salt Lake City, Utah, USA). The catheters were inserted into the skin model using the same technique as would be utilized in a patient. Results: The mean forces measured to dislodge the per-oral Flow 20 Pull Method, Entuit Thrive Balloon Retention, and button-type retention Ponsky replacement catheters were 35.6, 22.8, and 20.6 Newtons, respectively. The pull method per-oral gastrostomy catheter required significantly more pull force to dislodge than both the Ponsky button-type retention catheter and the Entuit balloon retention catheters. There was no significant difference in the pull force required to dislodge the Ponsky replacement catheter and the Entuit balloon retention catheter. Conclusions: Per-oral image-guided gastrostomy with pull-method button-type retention catheters may be the ideal choice in patients at high risk of tube dislodgment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Percutaneous Orthotopic IVC Construction in a Pediatric Patient with Symptomatic IVC Agenesis

Inferior vena cava agenesis is an uncommon condition usually attributed to embryologic dysgenesis. When symptomatic, unprovoked deep venous thrombosis and/or lower extremity venous congestion are the most frequent manifestations. Its rarity has precluded consensus regarding appropriate management. Symptomatic chronic venous congestion requires surgical construction of auxiliary venous pathways, which may involve substantial morbidity, prolonged recovery and extensive scarring. We report successful minimally invasive management via percutaneous endovascular orthotopic inferior vena cava construction in a pediatric patient, thereby obviating the need for surgery and its associated morbidity. Level of Evidence: Level IV, case study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Incidence and Consequence of Nontarget Embolization Following Bland Hepatic Arterial Embolization

Purpose: Estimate the incidence of nontarget embolization (NTE) as identified on immediate post-hepatic artery embolization CT. Materials and Methods: Two hundred hepatic embolizations performed with particles alone (bland embolization) in 147 patients between August 16, 2013 and August 26, 2014 with immediate post-procedure CT were retrospectively reviewed. Arterial anatomy, vessels treated, imaging findings of NTE, patient demographics, length of hospital stay following embolization, and procedure-related complications were recorded. The data were analyzed using two-sided t-tests and chi-squared tests. Results: Evidence of NTE was seen on post-procedure CT in 64 of 200 cases (64/200, 32%). Six organs were affected, with 69 discrete sites in 64 patients. The majority (49/69, 71.0%) involved the gallbladder. The mean length of hospital stay (LOS) for patients with and without NTE was 2.9 ± 1.5 nights (range 1–7) and 2.9 ± 2.3 nights (range 0–21), respectively (P = 0.81). NTE was more common following embolization of replaced or accessory hepatic vessels. There were three complications in the NTE group (3/64, 4.7%) following the embolization procedure, one of which was cholecystitis directly related to NTE. The other two were one incidence each of contrast-induced nephropathy and pneumonia. In the group without NTE, seven complications occurred (7/136, 5.1%, P = 0.889), including one death resulting from hepatic failure, two gastrointestinal bleeds, two hepatic abscesses, flash pulmonary edema, and pancreatitis. Conclusion: Unanticipated NTE is not uncommon after bland hepatic artery embolization, particularly after treating accessory or replaced vessels, but does not increase complications or LOS. Level of Evidence: Level 2b, Retrospective Cohort.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Exploration of target molecules for molecular imaging of inflammatory bowel disease

Highlights: {sup {yields}18}F-FDG PET could discriminate each inflamed area of IBD model mice clearly. {sup {yields}18}F-FDG PET could not discriminate the difference of pathogenic mechanism. {yields} Cytokines and cytokine receptors expression was different by pathogenic mechanism. {yields} Cytokines and cytokine receptors would be new target molecules for IBD imaging. -- Abstract: Molecular imaging technology is a powerful tool for the diagnosis of inflammatory bowel disease (IBD) and the efficacy evaluation of various drug therapies for it. However, it is difficult to elucidate directly the relationships between the responsible molecules and IBD using existing probes. Therefore, the development of an alternative probe that is able to elucidate the pathogenic mechanism and provide information on the appropriate guidelines for treatment is earnestly awaited. In this study, we investigated pathognomonic molecules in the intestines of model mice. The accumulation of fluorine-18 fluorodeoxyglucose ({sup 18}F-FDG) in the inflamed area of the intestines of dextran sulfate sodium (DSS)- or indomethacin (IND)-induced IBD model mice was measured by positron emission tomography (PET) and autoradiography to confirm the inflamed area. The results suggested that the inflammation was selectively induced in the colons of mice by the administration of DSS, whereas it was induced mainly in the ilea and the proximal colons of mice by the administration of IND. To explore attractive target molecules for the molecular imaging of IBD, we evaluated the gene expression levels of cytokines and cytokine receptors in the inflamed area of the intestines of both model mice. We found that the expression levels of cytokines and cytokine receptors were significantly increased during the progression of IBD, whereas the expression levels were decreased as the mucosa began to heal. In particular, the expression levels of these molecules had already changed before the symptoms of IBD appeared. In addition, the alterations of cytokine and cytokine receptor expression levels indicated differences in the expression pattern depending on the pathogenic mechanism or the region of inflammation (e.g., TNF-{alpha}). Our results suggest that these cytokines or cytokine receptors participate in the pathogenesis of IBD and are valuable biomarkers for the detection of the different circumstances underlying inflammation by the molecular imaging method. Finally, the development of an imaging probe for our target molecules is expected to improve our understanding of the inflammatory conditions of IBD.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Role of bone marrow cells in the development of pancreatic fibrosis in a rat model of pancreatitis induced by a choline-deficient/ethionine-supplemented diet

Highlights: Black-Right-Pointing-Pointer BMC-derived PSCs play a role in a rat CDE diet-induced pancreatitis model. Black-Right-Pointing-Pointer BMC-derived PSCs contribute mainly to the early stage of pancreatic fibrosis. Black-Right-Pointing-Pointer BMC-derived activated PSCs can produce PDGF and TGF {beta}1. -- Abstract: Bone marrow cell (BMC)-derived myofibroblast-like cells have been reported in various organs, including the pancreas. However, the contribution of these cells to pancreatic fibrosis has not been fully discussed. The present study examined the possible involvement of pancreatic stellate cells (PSCs) originating from BMCs in the development of pancreatic fibrosis in a clinically relevant rat model of acute pancreatitis induced by a choline-deficient/ethionine-supplemented (CDE) diet. BMCs from female transgenic mice ubiquitously expressing green fluorescent protein (GFP) were transplanted into lethally irradiated male rats. Once chimerism was established, acute pancreatitis was induced by a CDE diet. Chronological changes in the number of PSCs originating from the donor BMCs were examined using double immunofluorescence for GFP and markers for PSCs, such as desmin and alpha smooth muscle actin ({alpha}SMA), 1, 3 and 8 weeks after the initiation of CDE feeding. We also used immunohistochemical staining to evaluate whether the PSCs from the BMCs produce growth factors, such as platelet-derived growth factor (PDGF) and transforming growth factor (TGF) {beta}1. The percentage of BMC-derived activated PSCs increased significantly, peaking after 1 week of CDE treatment (accounting for 23.3 {+-} 0.9% of the total population of activated PSCs) and then decreasing. These cells produced both PDGF and TGF{beta}1 during the early stage of pancreatic fibrosis. Our results suggest that PSCs originating from BMCs contribute mainly to the early stage of pancreatic injury, at least in part, by producing growth factors in a rat CDE diet-induced pancreatitis model.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Pancreatic acinar cells-derived cyclophilin A promotes pancreatic damage by activating NF-κB pathway in experimental pancreatitis

Highlights: • CypA is upregulated in experimental pancreatitis. • CCK induces expression and release of CypA in acinar cell in vitro. • rCypA aggravates CCK-induced acinar cell death and inflammatory cytokine production. • rCypA activates the NF-κB pathway in acinar cells in vitro. - Abstract: Inflammation triggered by necrotic acinar cells contributes to the pathophysiology of acute pancreatitis (AP), but its precise mechanism remains unclear. Recent studies have shown that Cyclophilin A (CypA) released from necrotic cells is involved in the pathogenesis of several inflammatory diseases. We therefore investigated the role of CypA in experimental AP induced by administration of sodium taurocholate (STC). CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. In vitro, it was released from damaged acinar cells by cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced acinar cell necrosis, promoted nuclear factor (NF)-κB p65 activation, and increased cytokine production. In conclusion, CypA promotes pancreatic damage by upregulating expression of inflammatory cytokines of acinar cells via the NF-κB pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Hypermethylation of MST1 in IgG4-related autoimmune pancreatitis and rheumatoid arthritis

The serine/threonine kinase Mst1 plays important roles in the control of immune cell trafficking, proliferation, and differentiation. Previously, we reported that Mst1 was required for thymocyte selection and regulatory T-cell functions, thereby the prevention of autoimmunity in mice. In humans, MST1 null mutations cause T-cell immunodeficiency and hypergammaglobulinemia with autoantibody production. RASSF5C(RAPL) is an activator of MST1 and it is frequently methylated in some tumors. Herein, we investigated methylation of the promoter regions of MST1 and RASSF5C(RAPL) in leukocytes from patients with IgG4-related autoimmune pancreatitis (AIP) and rheumatoid arthritis (RA). Increased number of CpG methylation in the 5′ region of MST1 was detected in AIP patients with extrapancreatic lesions, whereas AIP patients without extrapancreatic lesions were similar to controls. In RA patients, we detected a slight increased CpG methylation in MST1, although the overall number of methylation sites was lower than that of AIP patients with extrapancreatic lesions. There were no significant changes of the methylation levels of the CpG islands in the 5′ region of RASSF5C(RAPL) in leukocytes from AIP and RA patients. Consistently, we found a significantly down-regulated expression of MST1 in regulatory T cells of AIP patients. Our results suggest that the decreased expression of MST1 in regulatory T cells due to hypermethylation of the promoter contributes to the pathogenesis of IgG4-related AIP. - Highlights: • Mst1 controls immune cells trafficking, cell proliferation and differentiation. • Autoimmune pancreatitis (AIP) is an idiopathic pancreatitis affecting multiple organs. • Decreased MST1 expression and increased CpG methylation of promoter of MST1 in AIP. • Slight increased CpG methylation of MST1 in rheumatoid arthritis patients. • MST1 contributes pathogenesis of IgG4-related AIP.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Gadolinium chloride ameliorates acute lung injury associated with severe acute pancreatitis in rats by regulating CYLD/NF-κB signaling

The present study was embarked on an investigation of the mechanisms behind the effects of Gadolinium chloride (GdCl{sub 3}) on lung injury associated with severe acute pancreatitis (SAP) in rats. Rats were randomly distributed into three groups: sham operation group (SO), SAP group and SAP treated with GdCl{sub 3} group (SAP + GdCl{sub 3}). Retrograde injection of 5% sodium taurocholate into the biliopancreatic duct was adopted to induce SAP. Lung tissue specimens were harvested for histological study, wet-to-dry weight ratio calculation and myeloperoxidase examination. Meanwhile, bronchoalveolar lavage fluid was analyzed for TNF-α and IL-1β activity and proteins content. Then the apoptosis ratio of alveolar macrophages (AMs) was detected. NF-κB activation and cylindromatosis (CYLD) expression in AMs were measured respectively. Results showed that GdCl{sub 3} treatment notably ameliorated lung injury induced by SAP, and simultaneously, the apoptosis ratio of AMs was significantly promoted. The NF-κB activation was obviously inhibited when CYLD expression was markedly up-regulated in AMs of SAP + GdCl{sub 3}. Negative correlation was analyzed between CYLD and NF-κB in both SAP and SAP + GdCl{sub 3}. These data demonstrate that GdCl{sub 3} ameliorates lung injury secondary to SAP in rats mainly by up-regulating CYLD expression and inhibiting NF-κB activation in AMs, which may play a vital role in lung injury. - Highlights: • GdCl{sub 3} ameliorates lung injury associated with SAP by inducing the apoptosis of AMs. • NF-kB activation can inhibit the apoptosis of AMs. • CYLD negatively regulates NF-kB activation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Caerulin-induced pro-inflammatory response in macrophages requires TRAF3-p38 signaling activation

Highlights: • Caerulin induces TRAF3 protein stabilization in mouse BMDMs. • Caerulin induces TRAF3 association with MKK3, mediating downstream p38 activation. • TRAF3 shRNA inhibits caerulin-induced pro-inflammatory cytokine production in BMDMs. • p38 blockage inhibits caerulin-induced pro-inflammatory cytokine production in BMDMs. • TRAF3 knockdown in caerulin-treated BMDMs alleviates cytotoxicity to pancreatic cells. Acute pancreatitis is a common threat to human health. Caerulin provokes severe inflammations, causing injuries to surrounding pancreatic cells. TNF receptor-associated factor 3 (TRAF3) is a highly versatile regulator of immune response. The current study aims to understand the potential effect of TRAF3 on caerulin-induced pro-inflammatory responses. In the primary-cultured mouse bone marrow–derived macrophages (BMDMs), caerulin induced TRAF3 protein stabilization, which formed a complex with mitogen-activated protein kinase kinase 3 (MKK3) to mediate downstream p38 activation. Lentiviral shRNA-mediated TRAF3 stable knockdown significantly attenuated caerulin-induced MKK3-p38 activation and production of several key pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-17. Remarkably, TRAF3 knockdown in caerulin-stimulated BMDMs also alleviated cytotoxicity to Panc02 and primary mouse pancreatic cells. Thus, TRAF3 is required for caerulin-induced p38 activation and macrophage-mediated pro-inflammatory responses. TRAF3 expression in macrophages could be a novel therapeutic target protein for the treatment of acute pancreatitis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Supplementation of pancreatic digestive enzymes alters the composition of intestinal microbiota in mice

Highlights: • Oral supplementation of pancrelipase alters composition of intestinal microbiota. • Over-represented taxa include bacteria promoting intestinal homeostasis. • Akkermansia muciniphila and Lactobacillus reuteri are over-represented. • Pro-inflammatory bacteria is inhibited by supplementation of pancrelipase. • Pancrelipase may help treat chronic pancreatitis by altering intestinal microbiota. Although pancreatic enzyme replacement therapy (PERT) is effective in the alleviation of pancreatic exocrine insufficiency (PEI)-related symptoms in patients with chronic pancreatitis, its mechanism of action is poorly understood. Recent studies suggest that the intestinal microbiota is associated with the pathogenesis of chronic pancreatitis. Therefore, we hypothesized that PERT exerts its effect by modifying the intestinal microbiota in addition to its presumed role in promoting fat and protein absorption. To explore the mechanism of action of PERT, we analyzed the intestinal microbiotas of two groups of mice treated with either pancrelipase or tap water by using 16S rRNA amplicon sequencing. The results revealed that the bacterial compositions of the pancrelipase-treated mice were significantly different from those of the control samples. Akkermansia muciniphila, a key beneficial bacterium in the intestinal tract, showed a higher relative abundance in the pancrelipase-treated samples than in the control samples. Lactobacillus reuteri, a widely used probiotic bacterium known to relieve intestinal inflammation, also showed a higher relative abundance in the pancrelipase-treated samples. These results suggested that PERT induces the colonization of beneficial bacteria, thereby contributing to the attenuation of PEI-associated symptoms in addition to improvement of the nutritional state.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Dexmedetomidine attenuates pancreatic injury and inflammatory response in mice with pancreatitis by possible reduction of NLRP3 activation and up-regulation of NET expression

Previous studies have shown that acute inflammation is associated with increased sympathetic activity, which in turn increases the inflammatory response and leads to organ damage. The present study aimed to investigate whether dexmedetomidine administration during acute pancreatitis (AP) lessens pancreatic pathological and functional injury and the inflammatory response, and to explore the underlying mechanisms.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

INT-777, a bile acid receptor agonist, extenuates pancreatic acinar cells necrosis in a mouse model of acute pancreatitis

Highlights: • TGR5 was mildly expressed in normal pancreatic tissue and increased significantly after caerulein-induced pancreatitis. • INT-777 attenuates the severity of acute pancreatitis and protects against acinar cell necrosis. • The mechanism appears to involve inhibition of ROS/NLRP3 inflammasome pathway. • INT-777 may be a therapeutic candidate for acute pancreatitis. Bile acids receptor TGR5 and its agonist INT-777, which has been found to be involved in the NLRP3 inflammasome pathway, play an important role in inflammatory diseases. However, the role of INT-777 in acute pancreatitis (AP) has not been reported. In this present study, we found that TGR5 was expressed in pancreatic tissue and increased after AP onset induced by caerulein and further evaluated the impact of INT-777 on the severity of AP. The results showed that INT-777 could reduce the severity of AP in mice, which was manifested as decreased pancreatic tissue damage as well as the decrease of serum enzymes (amylase and lipase), pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and the expression of necrosis related proteins (RIP3 and p-MLKL). Furthermore, we found that INT-777 reduced the reactive oxygen species (ROS) production in pancreatic acinar cells and inhibited the activation of NLRP3 inflammasome pathway. In conclusion, our data showed that INT-777 could protect pancreatic acinar cell against necrosis and reduce the severity of AP, which may be mediated by inhibiting ROS/NLRP3 inflammasome pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Autophagy impairment in pancreatic acinar cells causes zymogen granule accumulation and pancreatitis

Highlights: • Basal autophagy impairment causes zymogen granule accumulation in acinar cells. • Pancreas-specific autophagy impairment mice cause pancreatitis at 4 weeks of age. • Pancreas-specific autophagy impairment mice developed chronic pancreatitis. Basal autophagy degrades many kinds of proteins and organelles to maintain quality and plays important roles in cellular homeostasis. However, the impact of basal autophagy on zymogen granules in pancreatic acinar cells is unknown. In the present study, we examined the influence of autophagy impairment in acinar cells on zymogen granules and homeostasis of the pancreas, using mice with pancreas-specific autophagy impairment (Pdx1-Cre{sup +/-} Atg7{sup fl/fl} mice). The number of zymogen granules in acinar cells from these mice did not differ from that in acinar cells from their wild-type littermates at 3 weeks of age. However, the number of zymogen granules in acinar cells drastically increased at 4 weeks of age in mice with pancreas-specific autophagy impairment. In addition to the increased number of zymogen granules, serum lipase was elevated, and the pancreas became oedematous at 4 weeks of age, suggesting pancreatitis. After 5 weeks of age, acinar cell death was accelerated, and several histological features of chronic pancreatitis were observed, including glandular atrophy and pseudotubular complexes with fibrotic changes. In conclusion, the impairment of pancreas-specific basal autophagy caused spontaneous zymogen granule accumulation in acinar cells and pancreatitis, which eventually led to chronic pancreatitis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Double-stranded RNA-dependent kinase PKR activates NF-κB pathway in acute pancreatitis

The activation of transcription factor nuclear factor kappa B (NF-κB) occurs early in acute pancreatitis (AP) simultaneously with intracellular trypsinogen activation. Double-stranded RNA-dependent kinase (PKR) promotes the activation of NF-κB and the production of pro-inflammatory factors including tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). The rat and rat pancreatic AR42J cells were treated by cerulein to establish AP models, showing PKR increased. TNF-α, IL-6 and lactate dehydrogenase (LDH) in AP pancreatic tissues and cerulein-treated AR42J cells increased, while PKR knockdown in AR42J cells reversed cerulein-induced inflammatory response and pancreatic cell injury. In addition, inhibitor of kappa B kinase α (IKKα), phosphorylated P65 (p-P65), P65 increased in cerulein-treated AR42J cells. Meanwhile, in cerulein-treated AR42J cells, interaction between PKR and IKKα, as well as the co-localization and nuclear accumulation of PKR and P65, were detected. Furthermore, cerulein induced the phosphorylation and nuclear translocation of P65, which indicated the activation of NF-κB, while PKR knockdown hindered NF-κB activation to alleviate pancreatic cell injury. In summary, PKR might promote NF-κB activation via facilitating its phosphorylation and nuclear translocation, thus accelerated inflammatory response and pancreatic cell injury in AP, implying a novel molecular target for the treatment of AP.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Dynamic changes of proteasome and protective effect of bortezomib, a proteasome inhibitor, in mice with acute pancreatitis

Highlights: • 20s proteasome has a dynamic change in acute pancreatitis induced by caerulein. • Bortezomib, a proteasome inhibitor, alleviates two animal models of AP in mice. • The mechanism appears to involve inhibition of NF-κB signal pathway. • Bortezomib may be a therapeutic candidate for acute pancreatitis. The proteasome is involved in the activation of NF-κB and can regulate the progression of inflammatory diseases. However, the role of proteasome in acute pancreatitis (AP) has not been demonstrated. In this study, we first observed that the protein level and activity of proteasome 20S were increased significantly in pancreatic injury tissues after caerulein-induced mild acute pancreatitis (MAP) induction, which was in consistent with the expression of the NF-κB nucleoprotein and positively correlated with the severity of AP. Then, bortezomib, a classical proteasome inhibitor, was used to intervene the progression of MAP in mice. The results showed that bortezomib administration reduced the serum amylase and lipase levels and mitigated histopathological manifestation of pancreatic injury in mice. Meanwhile, bortezomib decreased the expression of NF-κB p65 nucleoprotein as well as total proteasome 20S protein, and inhibited the activity of 20S in pancreatic tissues. In addition, we found that bortezomib could protect pancreatic acinar cell against necrosis and mitigate the severity of AP in a severe acute pancreatitis model induced by sodium taurocholate hydrate. Taken together, our study for the first time confirmed that the proteasome participated in the pathogenesis of AP and its inhibitor bortezomib could protect against AP in mice.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Serum thyroid hormones levels are significantly decreased in pregnant rats with acute pancreatitis

Highlights: • Decreased serum thyroid hormones were derived from inflammation in animal APIP model. • Activation of MIF coincided with the extent of thyroid injury. • Self-healing may be occurred in thyroid injury during APIP in pregnant rats. Acute pancreatitis in pregnancy (APIP), which was thought to be a rare but severe disease, with a high perinatal mortality among maternal-fetuses. Our research aimed to study and assess thyroid injury in a rat model of APIP and its possible mechanisms. The APIP model was established by retrograde injection with sodium taurocholate. Sham-operated (SO) and APIP groups were performed at 3 time-points. Histological changes in the maternal thyroid and pancreas were assessed. The activities of serum amylase, lipase and levels of FT3, FT4, MDA, TNF-α and IL-1β were detected in maternal rats, and the expression of MIF, ICAM-1 and CD68 in the maternal thyroids were determined. In this study, maternal thyroid injury as well as pancreas injury occurred in a time-dependent manner. The activities of serum amylase, lipase and levels of MDA, TNF-α and IL-1β were markedly increased in acute pancreatitis rats, the levels of serum FT3 and FT4 were obviously decreased in APIP groups, and the expressions of MIF, ICAM-1 and CD68 were significantly increased in the thyroid of the APIP group. Ultrastructural thyroid injuries were observed in the APIP group. Our research suggests that thyroid injury is involved in the rat experimental model of APIP. The degree of thyroid dysfunction is associated with APIP, which may affect the prognosis of acute pancreatitis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Possible involvement of Enterococcus infection in the pathogenesis of chronic pancreatitis and cancer

Highlights: • We found some bacteria in pancreatic juice and tissue of pancreatic cancer. • We identified E. faecalis infection in pancreas with chronic pancreatitis. • Serum antibody titers against E. faecalis are increased in pancreatic diseases. • Addition of E. faecalis antigens increased expression of inflammatory cytokine. • E. faecalis might be a novel target for preventing chronic pancreatic diseases. (Aim) Bacterial infection underlies the pathogenesis of many human diseases, including acute and chronic inflammation. Here, we investigated a possible role for bacterial infection in the progression of chronic pancreatitis. (Materials and Methods) Pancreatic juice was obtained from patients with pancreatic cancer (n = 20) or duodenal cancer/bile duct cancer (n = 16) and subjected to PCR using universal primers for the bacterial 16S ribosomal RNA gene. Bacterial species were identified by PCR using bile samples from four pancreatic cancer patients. PCR products were subcloned into T-vectors, and the sequences were then analyzed. Immunohistochemical and serologic analyses for Enterococcus faecalis infection were performed on a large cohort of healthy volunteers and patients with chronic pancreatitis or pancreatic cancer and on mice with caerulein-induced chronic pancreatitis. The effect of E. faecalis antigens on cytokine secretion by pancreatic cancer cells was also investigated. (Results) We found that 29 of 36 pancreatic juice samples were positive for bacterial DNA. Enterococcus and Enterobacter species were detected primarily in bile, which is thought to be a pathway for bacterial infection of the pancreas. Enterococcus faecalis was also detected in pancreatic tissue from chronic pancreatitis and pancreatic cancer patients; antibodies to E. faecalis capsular polysaccharide were elevated in serum from chronic pancreatitis patients. Enterococcus-specific antibodies and pancreatic tissue–associated E. faecalis were detected in mice with caerulein-induced chronic pancreatitis. Addition of Enterococcus lipoteichoic acid and heat-killed bacteria induced expression of pro-fibrotic cytokines by pancreatic cancer cells in vitro. (Conclusion) Infection with E. faecalis may be involved in chronic pancreatitis progression, ultimately leading to development of pancreatic cancer.

60 APPLIED LIFE SCIENCES↗