Serum Lipase Activity Research Articles

Edible Bird's Nest Regulates Hepatic Cholesterol Metabolism through Transcriptional Regulation of Cholesterol Related Genes.

Objective Hypercholesterolemia is a strong risk factor for cardiovascular diseases. Side effects associated with the use of pharmaceutical agents can cancel out their benefits. Dietary management of hypercholesterolemia is, therefore, receiving much attention due to fewer side effects. In this study, we explored the effectiveness of edible bird's nest (EBN) in the prevention of hypercholesterolemia in rats. Methods High-cholesterol diet (HCD) (4.5% cholesterol and 0.5% cholic acid) with or without EBN (low (2.5%) or high dose (20%)) was given to rats for 12 weeks, and their weights were observed. Simvastatin (10 mg/kg/day) was administered for the same period as a control drug. Serum and tissue samples were collected at the end of the study, from which biochemical parameters (lipid profiles, oxLDL, liver enzymes, urea, creatinine, uric acid, and lipase activity) and hepatic mRNA levels were measured. Results The HCD group had higher levels of serum lipids, liver enzymes, uric acid, urea, and lipase activity compared with those of the other groups. The hepatic mRNA levels of cholesterol metabolism genes (APOB, PCSK9, HMGCR, LDLR, and CYP7A1) in the HCD group also tended toward increased cholesterol production and reduced cholesterol clearance. EBN, especially the highest dose, attenuated the HCD-induced changes, partly through improving the transcriptional regulation of hepatic cholesterol metabolism genes with fold changes of 0.7, 0.6, 0.5, 1.7, and 2.7, respectively, in comparison to the HCD group. In fact, EBN produced better results than simvastatin. Conclusion Thus, the results suggest that EBN can regulate cholesterol metabolism and, therefore, be a source of functional ingredients for the management of hypercholesterolemia.

Human umbilical cord mesenchymal stem cells-derived exosomes for treating traumatic pancreatitis in rats

BackgroundThe therapeutic and protective effects of human umbilical cord mesenchymal stem cells-exosomes (hucMSC-Exs) on traumatic pancreatitis (TP) remain unknown. Here, we established a rat model of TP and evaluated and compared the therapeutic effects of hUC-MSCs and hucMSC-Exs.MethodsHucMSC-Exs were obtained by ultracentrifugation and identified using transmission electron microscopy and western blot analysis. TP rats were treated by tail vein injection of hUC-MSCs and hucMSC-Exs. Their homing in rats was observed by performing fluorescence microscopy. The degree of pancreatic tissue damage was assessed by HE staining, the expression levels of amylase, lipase, and inflammatory cytokines were detected by ELISA, apoptosis was detected by TUNEL assay, and the expression levels of various apoptosis-related proteins were detected by western-blot. The expression levels of apoptosis-related molecular markers were detected by RT-qPCR.ResultsThe colonization of exosomes was observed in pancreatic tissue. Compared to TP group, the histopathological score of pancreas was significantly decreased in the TP + hUC-MSCs group and TP + hucMSC-Exs group (P < 0.05). Compared to TP group, the activity of serum amylase and lipase was significantly decreased (P < 0.05). The expression levels of IL-6 and TNF-α were significantly decreased, while those of IL-10 and TGF-β were significantly increased (P < 0.05). The apoptosis index of the TP group was significantly increased (P < 0.05), whereas that of the TP + hUC-MSCs and TP + hucMSC-Exs groups was significantly decreased (P < 0.05). Compared to TP group, the expression levels of Bax, Bcl-2, and Caspase-3 were significantly decreased in the TP + hUC-MSCs group and TP + hucMSC-Exs group (P < 0.05).ConclusionHucMSC-Exs can colonize injured pancreatic tissue, inhibit the apoptosis of acinar cells, and control the systemic inflammatory response to facilitate the repair of pancreatic tissue.

Systemic injury caused by taurocholate-induced severe acute pancreatitis in rats.

Systemic injury plays a central role in severe acute pancreatitis (SAP). Retrograde biliopancreatic duct infusion of sodium taurocholate (NaT) is commonly used to establish SAP animal models. To better characterize the systemic injury in this model, SAP was induced in Sprague-Dawley rats by NaT administration (3.5 or 5%), followed by sacrifice at 3, 6, 9, 12, 24, 48 and 72 h. Normal saline was used as a control in Sham-operated rats. The mortality rate, ascites volume, and serum and ascitic fluid amylase and lipase activities were assessed. Multiple organ dysfunction, including dysfunction of the pancreas, lung, ileum, liver, and kidney, was investigated using hematoxylin and eosin staining. The interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in the ascitic fluid, serum, and ileum tissues were evaluated using an enzyme-linked immunosorbent assay (ELISA). Tight junction proteins, zonula occludens-1 (ZO-1) and occludin, in ileum tissues were studied using immunofluorescence. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CRE) and urea levels were measured using an automatic biochemical analyzer. The results of the present study indicated that both 3.5 and 5% NaT could induce a stable elevation of pancreatitis indices, with histopathological injury of the pancreas, lungs and ileum (5% NaT). The ascitic fluid levels of IL-6 and IL-1β were increased in the 5% NaT group. ALT and AST levels increased temporarily and recovered in 72 h, without a significant increase in CRE and urea levels or apparent hepatic and renal pathological injury. In conclusion, rats with NaT-induced SAP have characteristics of necrotizing hemorrhagic pancreatitis with multiple organ injuries, including inflammatory lung injury, ischemic intestinal injury and slight liver and kidney injuries.

Paeoniflorin Can Improve Acute Lung Injury Caused by Severe Acute Pancreatitis through Nrf2/ARE Pathway.

Objective To evaluate the potential therapeutic effect of paeoniflorin on acute lung injury induced by severe acute pancreatitis (SAP) and to initially explore the possible protective mechanisms of paeoniflorin. Method The SAP lung injury rat model was established by retrograde injection of 5% sodium taurocholate to the cholangiopancreatic duct. H&E staining was used to detect pathological changes in rat lung tissue. W/D ratio method, serum amylase (AMY), and lipase activity were used to assess the degree of lung injury in rats. Oxidation indicators such as LDH, MDA, and SOD in lung tissue were measured. Levels of inflammatory factors TNF-α, IL-6, and IL-10 were measured in bronchoalveolar lavage fluid (BALF). At the same time, Western blot was used to detect the expression of related proteins in the Nrf2/ARE signaling pathway. Results In SAP rats, paeoniflorin treatment could significantly alleviate lung injury conditions such as pulmonary edema and inflammatory cell infiltration in lung tissue and reduce serum amylase and lipase activities. Paeoniflorin can reduce the content of LDH and MDA in lung tissue and increase the content of SOD. In addition, ELISA results showed that paeoniflorin could inhibit the levels of TNF-α and IL-6 in BALF and upregulate the levels of IL-10. Paeoniflorin could upregulate the expression of Nrf2/ARE signaling pathway proteins Cyt-Nrf2, HO-1, and NQO1 in lung tissue of SAP rats. Conclusion Paeoniflorin may improve acute lung injury in rats with severe pancreatitis by inhibiting inflammation and oxidative stress response. These effects may be related to activating the Nrf2/ARE signaling pathway.

Effects of medical history and clinical factors on serum lipase activity and ultrasonographic evidence of pancreatitis: Analysis of 234 dogs

BackgroundLipase measurements and ultrasonographic (US) evidence of pancreatitis correlate poorly.ObjectivesIdentify explanations for discrepant lipase and pancreatic US results.AnimalsTwo hundred and thirty‐four dogs with gastrointestinal signs.MethodsA retrospective study was conducted, in which lipase activity and US were performed within 30 hours. Medical history, clinical examination results, lipase activity, and US results were recorded.ResultsLipase and US results were weakly correlated (r s = .25, P < .001). At both evaluated time cut‐offs, median lipase activities were significantly higher with shorter durations of clinical signs before presentation (≤2 days, 334 U/L; >2 days, 118 U/L; P = .03; ≤7 days, 334 U/L; >7 days, 99 U/L; P = .004), but US was not significantly more frequently positive. For both cut‐offs (>216/≤216 U/L, >355/≤355 U/L; reference range, 24‐108 U/L), median disease duration was significantly shorter (3 vs 4 days) with higher lipases. Previous pancreatitis episodes were significantly associated with an US diagnosis of pancreatitis (P = .04), but median lipase activities were not significantly higher (386 U/L vs 153 U/L; P = .06) in these dogs. Pancreatic US was significantly more often positive when the request contained “suspicion of pancreatitis” (P < .001) or “increased lipase” (P = .01). Only changes in pancreatic morphology, echogenicity, and peripancreatic mesentery were significantly associated with a positive US diagnosis, and also had significantly higher lipase activities.Conclusions and Clinical ImportanceDuration of clinical signs before presentation differently affects laboratory and US evidence of pancreatitis. Previous pancreatitis episodes and information given to radiologists influence US results. These findings can be helpful for future studies on pancreatitis in dogs.

Role of CaMK II in pancreatic injury in mice with severe acute pancreatitis

To investigate the expression of Ca2+/calmodulin-dependent protein kinase II (CaMK Ⅱ) in pancreatic tissues of mice with severe acute pancreatitis (SAP) and explore the protective effect of KN93, a CaMK Ⅱ inhibitor, against pancreatic injury in SAP and the possible mechanism. Thirty-six healthy male C57 mice were randomly divided into sham operation group, SAP group, KN93 group and SAP + KN93 group (n=9). Serum and pancreatic tissue samples were collected 24 h after modeling. The pathological changes in the pancreatic tissues were observed using HE staining. Serum lipase and amylase activities and the levels of inflammatory factors were detected using ELISA. Western blotting was used to detect the expressions of CaMK Ⅱ, p-CaMK Ⅱ, p-NF-κB, MAPK and p-MAPK in mouse pancreas. Compared with those in sham operation group, the expressions of p-CaMK Ⅱ, p-NF-κB and p-MAPK were significantly increased in SAP group (P < 0.05). KN93 treatment obviously alleviated pathological injuries of the pancreas in SAP mice, and significantly lowered serum levels of lipase, amylase and inflammatory factors (TNF-α and IL-6) and phosphorylation levels of NF-κB, ERK and MAPK proteins (P < 0.05). The activity of CaMK Ⅱ is significantly increased in the pancreatic tissue of SAP mice. KN93 can alleviate pancreatic injury and inflammation in SAP mice possibly through the ERK/MAPK signaling pathway.

Vanillin modulates activities linked to dysmetabolism in psoas muscle of diabetic rats

Skeletal muscles are important in glucose metabolism and are affected in type 2 diabetes (T2D) and its complications. This study investigated the effect of vanillin on redox imbalance, cholinergic and purinergic dysfunction, and glucose-lipid dysmetabolism in muscles of rats with T2D. Male albino rats (Sprague–Dawley strain) were fed 10% fructose ad libitum for 2 weeks before intraperitoneally injecting them with 40 mg/kg streptozotocin to induce T2D. Low (150 mg/kg bodyweight (BW)) and high (300 mg/kg BW) doses of vanillin were orally administered to diabetic rats. Untreated diabetic rats and normal rats made up the diabetic control (DC) and normal control (NC) groups, respectively. The standard antidiabetic drug was metformin. The rats were humanely put to sleep after 5 weeks of treatment and their psoas muscles were harvested. There was suppression in the levels of glutathione, activities of SOD, catalase, ENTPDase, 5′Nucleotidase and glycogen levels on T2D induction. This was accompanied by concomitantly elevated levels of malondialdehyde, serum creatine kinase-MB, nitric oxide, acetylcholinesterase, ATPase, amylase, lipase, glucose-6-phosphatase (G6Pase), fructose-1,6-biphophastase (FBPase) and glycogen phosphorylase activities. T2D induction further resulted in the inactivation of fatty acid biosynthesis, glycerolipid metabolism, fatty acid elongation in mitochondria and fatty acid metabolism pathways. There were close to normal and significant reversals in these activities and levels, with concomitant reactivation of the deactivated pathways following treatment with vanillin, which compared favorably with the standard drug (metformin). Vanillin also significantly increased muscle glucose uptake ex vivo. The results suggest the therapeutic effect of vanillin against muscle dysmetabolism in T2D as portrayed by its ability to mitigate redox imbalance, inflammation, cholinergic and purinergic dysfunctions, while modulating glucose-lipid metabolic switch and maintaining muscle histology.

MP33-06 MACROPHAGE INHIBITORY CYTOKINE-1 INDUCED BY A HIGH-FAT DIET PROMOTES PROSTATE CANCER PROGRESSION BY STIMULATING TUMOR-PROMOTING CYTOKINE PRODUCTION FROM TUMOR STROMAL CELLS

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I (MP33)1 Sep 2021MP33-06 MACROPHAGE INHIBITORY CYTOKINE-1 INDUCED BY A HIGH-FAT DIET PROMOTES PROSTATE CANCER PROGRESSION BY STIMULATING TUMOR-PROMOTING CYTOKINE PRODUCTION FROM TUMOR STROMAL CELLS Mingguo Huang, Shintaro Narita, Atsushi Koizumi, Taketoshi Nara, Kazuyuki Numakura, and Tomonori Habuchi Mingguo HuangMingguo Huang More articles by this author , Shintaro NaritaShintaro Narita More articles by this author , Atsushi KoizumiAtsushi Koizumi More articles by this author , Taketoshi NaraTaketoshi Nara More articles by this author , Kazuyuki NumakuraKazuyuki Numakura More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002042.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recent studies have indicated that a high-fat diet (HFD) and/or HFD-induced obesity may influence prostate cancer (PCa) progression, but the role of HFD in PCa microenvironment is unclear. This study aimed to delineate the molecular mechanisms of PCa progression under HFD milieus and define the stromal microenvironment focusing on macrophage inhibitory cytokine-1 (MIC-1) activation. METHODS: We investigated the effects of HFD on PCa stromal microenvironment and MIC-1 signaling activation using PC-3M-luc-C6 PCa model mice fed with HFD or control diet. Further, we explored the effect of periprostatic adipocytes derived from primary PCa patients on activation and cytokine secretion of prostate stromal fibroblasts. Expression patterns and roles of MIC-1 signaling on human PCa stroma activation and progression were also investigated. RESULTS: HFD stimulated PCa cell growth and invasion as a result of upregulated MIC-1 signaling and subsequently increased the secretion of interleukin (IL)-8 and IL-6 from prostate stromal fibroblasts in PC-3M-luc-C6 PCa mouse model. In addition, periprostatic adipocytes directly stimulated MIC-1 production from PC-3 cells and IL-8 secretion in prostate stromal fibroblasts through the upregulation of adipose lipolysis and free fatty acid release. The increased serum MIC-1 was significantly correlated with human PCa stroma activation, high serum IL-8, IL-6, and lipase activity, advanced PCa progression, and high body mass index of the patients. Glial-derived neurotrophic factor receptor α-like (GFRAL), a specific receptor of MIC-1, was highly expressed in both cytoplasm and membrane of PCa cells and surrounding stromal fibroblasts, and the expression level was decreased by androgen deprivation therapy and chemotherapy. CONCLUSIONS: HFD-mediated activation of the PCa stromal microenvironment through metabolically upregulated MIC-1 signaling by increased available free fatty acids may be a critical mechanism of HFD and/or obesity-induced PCa progression. Source of Funding: This work was supported by the Japan Society for the Promotion of Science (JSPS, Grant No.: 16H02679, 16K10992, 19K09663) and AMED-CREST, Japan Agency for Medical Research and Development (AMED) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e608-e608 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mingguo Huang More articles by this author Shintaro Narita More articles by this author Atsushi Koizumi More articles by this author Taketoshi Nara More articles by this author Kazuyuki Numakura More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement Loading ...

Diabetic Bone Marrow Cell Injection Accelerated Acute Pancreatitis Progression

Acute pancreatitis (AP) is one of the leading causes of hospital admission, 20% of which could progress to the severe type with extensive acinar cell necrosis. Clinical studies have reported that diabetes is an independent risk factor of the incidence of AP and is associated with higher severity than nondiabetic subjects. However, how diabetes participates in AP progression is not well defined. To investigate this question, wild-type (wt) and diabetic db/db mice at the age of 16 weeks were used in the study. AP was induced in wt recipients by 10 injections of 50 μg/kg caerulein with a 1 h interval. One hour after the last caerulein injection, bone marrow cells (BMC) isolated from wt and db/db mice were injected intraperitoneally into the recipients (1 × 107cells/recipient). The recipients with no BMC injection served as controls. Thirteen hours after BMC injection, serum lipase activity was 1.8- and 1.3-folds higher in mice that received db/db BMC, compared with those with no injection and wt BMC injection, respectively (p ≤ 0.02 for both). By H&E staining, the overall severity score was 14.7 for no cell injection and 16.6 for wt BMC injection and increased to 22.6 for db/db BMC injection (p ≤ 0.002 for both). In particular, mice with db/db BMC injection developed more acinar cell necrosis and vacuolization than the other groups (p ≤ 0.03 for both). When sections were stained with an antibody against myeloperoxidase (MPO), the density of MPO+ cells in pancreatitis was 1.9- and 1.6-folds higher than wt BMC and no BMC injection groups, separately (p ≤ 0.02 for both). Quantified by ELISA, db/db BMC produced more IL-6, GM-CSF, and IL-10 compared with wt BMC (p ≤ 0.04 for all). In conclusion, BMC of db/db mice produced more inflammatory cytokines. In response to acinar cell injury, diabetic BMC aggravated the inflammation cascade and acinar cell injury, leading to the progression of acute pancreatitis.

The Anti-Obesity Effects of Lemon Fermented Products in 3T3-L1 Preadipocytes and in a Rat Model with High-Calorie Diet-Induced Obesity.

Lemon (Citrus limon) has antioxidant, immunoregulatory, and blood lipid-lowering properties. This study aimed to determine the effect of the lemon fermented product (LFP) which is lemon fermented with Lactobacillus OPC1 to prevent obesity. The inhibition of lipid accumulation in 3T3-L1 adipocytes is examined using a Wistar rat model fed a high-fat diet to verify the anti-obesity efficacy and mechanism of LFP. Here, it was observed that LFP reduced cell proliferation and inhibited the lipid accumulation (8.3%) of 3T3-L1 adipocytes. Additionally, LFP reduced body weight (9.7%) and fat tissue weight (25.7%) of rats; reduced serum TG (17.0%), FFA (17.9%), glucose (29.3%) and ketone body (6.8%); and increased serum HDL-C (17.6%) and lipase activity (17.8%). LFP regulated the mRNA expression of genes related to lipid metabolism (PPARγ, C/EBPα, SREBP-1c, HSL, ATGL, FAS, and AMPK). Therefore, LFP reduces body weight and lipid accumulation by regulating the mRNA expression of genes related to lipid metabolism. Overall, our results implicate LFP as a potential dietary supplement for the prevention of obesity.

Effects of dietary nicotinic acid supplementation on meat quality, carcass characteristics, lipid metabolism, and tibia parameters of Wulong geese

The purpose of this study was to evaluate the effects of nicotinic acid (NA) supplementation on the meat quality, carcass characteristics, lipid metabolism, and tibia parameters in Wulong geese. A total of 360 twenty-nine-day-old Wulong geese were randomly divided into 6 treatments, and each treatment included 6 pens with 10 birds per pen. Birds were fed a basal diet supplemented with 0, 20, 40, 60, 80, or 100 mg/kg NA for 12 wk. Dietary NA supplementation linearly decreased L* value and increased pH and water-holding capacity in the breast muscle (P < 0.05). Increasing NA levels linearly and quadratically decreased shear force of breast muscle (P < 0.001). Dietary NA supplementation linearly reduced the thickness of subcutaneous fat plus the skin and percentage of abdominal fat, and enhanced the width of intermuscular fat band (P < 0.001). Dietary NA addition linearly and quadratically increased intramuscular fat (IMF) content (P ≤ 0.001). Increasing NA levels decreased serum total cholesterol and low-density lipoprotein cholesterol levels and increased serum lipase activity and hepatic mRNA expression of lipoprotein lipase in a linear manner (P < 0.05). There were linear and quadratic effects in serum triglycerides and high-density lipoprotein cholesterol (HDL-C) levels and malate dehydrogenase activity with the NA addition (P < 0.05). Feeding the NA-supplemented-diets linearly increased tibia length, circumference, fat-free dry weight, and ash content (P < 0.001). There were linear and quadratic increases in Ca and P contents with the NA supplementation (P < 0.05). According to the quadratic regression analyses fitted to shear force, IMF content, serum triglycerides and HDL-C levels, and tibial Ca and P contents, the optimal dietary NA supplementation was 80 to 90 mg/kg. In conclusion, NA addition enhanced meat quality and IMF content, regulated lipid metabolism, and increased tibia quality of Wulong geese. The dosage of 80 mg/kg NA in Wulong geese aged 5 to 16 wk was recommended.

Betulinic Acid Ameliorates the Severity of Acute Pancreatitis via Inhibition of the NF-κB Signaling Pathway in Mice.

Acute pancreatitis (AP) is an inflammatory disorder, involving acinar cell death and the release of inflammatory cytokines. Currently, there are limited effective therapeutic agents for AP. Betulinic acid (BA) is a pentacyclic triterpenoid extracted from Betula platyphylla that has been shown to have anti-inflammatory effects. In this study, we aimed to investigate the effects of BA on AP and elucidate the potential underlying mechanisms. AP was induced in mice through six intraperitoneal injections of cerulein. After the last cerulein injection, the mice were sacrificed. Our results revealed that pre- and post-treatment with BA significantly reduced the severity of pancreatitis, as evidenced by a decrease in histological damage in the pancreas and lung, serum amylase and lipase activity and pancreatic myeloperoxidase activity. Furthermore, BA pretreatment reduced proinflammatory cytokine production, augmentation of chemokines, and infiltration of macrophages and neutrophils in the pancreas of AP mice. In addition, mice that were pretreated with BA showed a reduction in Iκ-Bα degradation and nuclear factor-kappa B (NF-κB) binding activity in the pancreas. Moreover, BA reduced the production of proinflammatory cytokines and NF-κB activation in pancreatic acinar cells (PACs). These findings suggest that BA may have prophylactic and therapeutic effects on AP via inhibition of the NF-κB signaling pathway.

Poly(ADP-Ribose) Polymerase 1 Promotes Inflammation and Fibrosis in a Mouse Model of Chronic Pancreatitis.

Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized by ductal obstructions, tissue fibrosis, atrophy and exocrine and endocrine pancreatic insufficiency. However, our understanding is very limited concerning the disease’s progression from a single acute inflammation, via recurrent acute pancreatitis (AP) and early CP, to the late stage CP. Poly(ADP-ribose) polymerase 1 (PARP1) is a DNA damage sensor enzyme activated mostly by oxidative DNA damage. As a co-activator of inflammatory transcription factors, PARP1 is a central mediator of the inflammatory response and it has also been implicated in acute pancreatitis. Here, we set out to investigate whether PARP1 contributed to the pathogenesis of CP. We found that the clinically used PARP inhibitor olaparib (OLA) had protective effects in a murine model of CP induced by multiple cerulein injections. OLA reduced pancreas atrophy and expression of the inflammatory mediators TNFα and interleukin-6 (IL-6), both in the pancreas and in the lungs. Moreover, there was significantly less fibrosis (Masson’s trichrome staining) in the pancreatic sections of OLA-treated mice compared to the cerulein-only group. mRNA expression of the fibrosis markers TGFβ, smooth muscle actin (SMA), and collagen-1 were markedly reduced by OLA. CP was also induced in PARP1 knockout (KO) mice and their wild-type (WT) counterparts. Inflammation and fibrosis markers showed lower expression in the KO compared to the WT mice. Moreover, reduced granulocyte infiltration (tissue myeloperoxidase activity) and a lower elevation of serum amylase and lipase activity could also be detected in the KO mice. Furthermore, primary acinar cells isolated from KO mice were also protected from cerulein-induced toxicity compared to WT cells. In summary, our data suggest that PARP inhibitors may be promising candidates for repurposing to treat not only acute but chronic pancreatitis as well.

Macrophage inhibitory cytokine-1 induced by a high-fat diet promotes prostate cancer progression by stimulating tumor-promoting cytokine production from tumor stromal cells.

BackgroundRecent studies have indicated that a high‐fat diet (HFD) and/or HFD‐induced obesity may influence prostate cancer (PCa) progression, but the role of HFD in PCa microenvironment is unclear. This study aimed to delineate the molecular mechanisms of PCa progression under HFD milieus and define the stromal microenvironment focusing on macrophage inhibitory cytokine‐1 (MIC‐1) activation.MethodsWe investigated the effects of HFD on PCa stromal microenvironment and MIC‐1 signaling activation using PC‐3M‐luc‐C6 PCa model mice fed with HFD or control diet. Further, we explored the effect of periprostatic adipocytes derived from primary PCa patients on activation and cytokine secretion of prostate stromal fibroblasts. Expression patterns and roles of MIC‐1 signaling on human PCa stroma activation and progression were also investigated.ResultsHFD stimulated PCa cell growth and invasion as a result of upregulated MIC‐1 signaling and subsequently increased the secretion of interleukin (IL)‐8 and IL‐6 from prostate stromal fibroblasts in PC‐3M‐luc‐C6 PCa mouse model. In addition, periprostatic adipocytes directly stimulated MIC‐1 production from PC‐3 cells and IL‐8 secretion in prostate stromal fibroblasts through the upregulation of adipose lipolysis and free fatty acid release. The increased serum MIC‐1 was significantly correlated with human PCa stroma activation, high serum IL‐8, IL‐6, and lipase activity, advanced PCa progression, and high body mass index of the patients. Glial‐derived neurotrophic factor receptor α‐like (GFRAL), a specific receptor of MIC‐1, was highly expressed in both cytoplasm and membrane of PCa cells and surrounding stromal fibroblasts, and the expression level was decreased by androgen deprivation therapy and chemotherapy.ConclusionHFD‐mediated activation of the PCa stromal microenvironment through metabolically upregulated MIC‐1 signaling by increased available free fatty acids may be a critical mechanism of HFD and/or obesity‐induced PCa progression.

Dietary laminarin administration to enhance the immune responses, promote growing and strengthen physique in Ictalurus punctatus

In this study, the different dosage of laminarin groups (normal fodder group (Control), normal fodder add 1 g laminarin group (AL1), normal fodder add 2 g laminarin group (AL2), normal fodder add 4 g laminarin group (AL4) and normal fodder add 8 g laminarin group (AL8)) were set. After 45 days, the growth, enzyme activity and immune-related gene were measured to assess the effect of feeding laminarin on Ictalurus punctatus. Laminarin (4 g dosage) can significantly increase body length (p < .05) and BMI (body mass index) value in 8 g dosage group (p < .05). Lysozyme, acid phosphatase, aspartate aminotransferase, catalase, superoxide dismutase, pepsin, amylase and trypsin activity are increased with the dosage of laminarin increasing, and have a significant difference at the dosage of 4 g and 8 g group (p < .001). However, the serum cortisol content, alkaline phosphatase and lipase activity have a significant inhibition in high-dosage groups (p < .001). The expression of TLR5 gene in group of 4 g dosage was significantly upregulated (p < .05). The expression of SOCs gene in groups of 2 g (p < .05), 4 g (p < .001) and 8 g (p < .001) dosage was significantly downregulated. The expression of IGF2 and STAT5 genes was significantly upregulated in high-dosage laminarin groups. Generally, larminarin enhances the immune response, reduces the rate of energy decomposition required and improves food absorption. This shows that the larminarin improves the physical quality and increases productivity of I. punctatus, and offers great potential for application in the aquaculture industry.

Dietary sodium butyrate nanoparticles enhanced growth, digestive enzyme activities, intestinal histomorphometry, and transcription of growth-related genes in Nile tilapia juveniles

Feed supplementation is so important to sustain the aquaculture industry. Research studies showed that sodium butyrate used as a feed supplement could improve the growth and health condition of fish. It is hypothesized that the use of sodium butyrate nanoparticles (SB-NP) as a feed supplement may improve the overall fish performance and welfare status than the ordinary-sized one. The current study was done to assess the effects of dietary supplementation with SB-NP on growth, digestive enzyme activities, intestinal histomorphometry, and expression of some growth-related genes of Nile tilapia (Oreochromis niloticus) juveniles. Fish (25.3 ± 0.35 g) were fed on diets supplemented with 0.0 (control), 0.5, 1.0, 1.5, and 2.0 mg SB-NP/kg diet up to apparent satiation (thrice per a day) for eight weeks. Growth–stimulating effects of dietary SB-NP were significantly noted in regard to the final body weight, weight gain percentage, and specific growth rate with optimum levels of 1.0–1.5 mg SB-NP/kg diet. Furthermore, fish groups fed on diets supplemented with SB-NP significantly enhanced the feed intake over those fed on the control diet alongside with no significant differences in feed conversion ratio among the experimental groups. Pairwise comparisons with the control group showed that serum amylase, lipase, and protease activities were significantly increased (P < 0.05) with increasing the dietary levels of BS-NP, and their maximum activities were observed at levels of 1.0–1.5 mg/kg diet. The intestinal histomorphometric features of fish groups fed diets enriched with SB-NP showed increased villi length/width, crypt depth, surface absorption area, and goblet cells than the control group with optimum levels of 1.0–1.5 mg/kg diet. The expressions of growth-related genes in the stomach (ghrelin) and the liver (GH and IGF-1) were significantly (P < 0.05) higher in SB-NP supplemented groups after eight weeks, with highest expressions at 1.0–1.5 mg/kg diet. According to the regression fitting curve, the current study recommends using the dietary SB-NP with optimum values of 1.3–1.5 mg/kg diet to enhance the growth performance with no side effects on the health status of Nile tilapia.

Fraxetin prevented sodium fluoride-induced chronic pancreatitis in rats: Role of anti-inflammatory, antioxidant, antifibrotic and anti-apoptotic activities

Chronic pancreatitis is considered a common gastrointestinal disorder, with significant morbidity and mortality. Fluoride is an important agent for the development of our body systems, especially for bone and teeth, however on its excess consumption, it deposits in different body tissues, especially the pancreas, causing its chronic inflammation and destruction. Fraxetin proved to possess versatile activities including; antioxidant, anti-inflammatory, antifibrotic, and anti-apoptotic activities. In the present study, we have evaluated the fraxetin potentiality to prevent fluoride-induced chronic pancreatitis in rats, by evaluating animal body weights and body weight gain rate, serum amylase, and lipase activities, pancreatic oxidative stress markers, cytokines, apoptotic markers, myeloperoxidase, and hydroxyproline levels, and histopathological changes. Nine-weeks-old male Wistar rats drank distilled water containing 500 ppm sodium fluoride (NaF) for 60 days to induce chronic pancreatitis. Oral fraxetin (20, 40, and 80 mg/kg/day) received simultaneously to prevent chronic pancreatitis development. Fraxetin in a dose-dependent manner alleviated chronic pancreatitis induced by NaF, as it restored the decreased body weight and weight gain rate, decreased the elevated serum amylase and lipase activities, pancreatic IL-6, TNF-α, MDA, caspase-3, MPO and hydroxyproline levels, and Bax/Bcl-2 ratio, enhanced pancreatic CAT and SOD activities, and GSH levels, besides it augmented the elevated IL-10 level, with the restoration of normal pancreatic architecture. Therefore, fraxetin could be a promising agent recommended for the prevention of fluoride-induced chronic pancreatitis in endemic areas.

Detection of lipase activity in human serum based on a ratiometric fluorescent probe

CARA can monitor lipase activity through hydrolyzing the ester bond to interrupt the FRET process.

The mechanism underlying hypaconitine-mediated alleviation of pancreatitis-associated lung injury through up-regulating aquaporin-1/TNF-α.

Acute pancreatitis-associated lung injury (APALI) is one of the most common and most dangerous form of extra-pancreatic organ damage in severe acute pancreatitis (SAP). The treatment options for SAP were limited thus far; as a result, approximately 60%-80% of patients with SAP would die within a week. Hypaconitine (HC), one of the most important active ingredients in a Mongolian traditional medicine Radix Aconiti Kusnezoffii has an excellent anti-inflammatory effect. To ascertain whether HC has a protective effect against APALI, we investigated the therapeutic effects and the underlying mechanisms in vivo and in vitro and attempted to elucidate the mechanism in detail. In this study, APALI rats and human pulmonary microvascular endothelial cells were treated with therapeutic doses of HC after establishing a model with sodium taurocholate and lipopolysaccharide, respectively. Serum amylase and lipase activity, lung wet/dry weight ratio, lung myeloperoxidase activity, and pancreatic and lung histopathological changes showed that HC alleviated APALI in a dose-dependent way, which can be abolished by an aquaporin-1 (AQP-1) knockdown. The results of the reverse transcriptase polymerase chain reaction, Western blot, and immunohistochemical staining confirmed the expression of AQP-1, a kind of transmembrane protein that mainly distributed in the membranes of pulmonary cells and contributed to maintain water balance in the body by interacting with tumor necrosis factor-alpha (TNF-α), is negatively associated with APALI. On the contrary, HC treatment up-regulated AQP-1 expression and down-regulated the TNF-α expression as a consequence in APALI. These results suggest that HC has a good anti-inflammatory therapeutic effect on APALI with a possible underlying mechanism that affects the AQP-1/TNF-α pathway.

Effect of water salinity on enzymatic and hormonal indices of (Oncorhynchus mykiss) fingerlings

Salinity is one of the stressful environmental factors, which affects life, metabolism, and distribution of aquatic animals. In this study, the effects of different levels of water salinity were investigated on serum biochemical parameters in rainbow trout (Oncorhynchus mykiss) fingerlings. For this, the fish (5.53±0.057 g) were exposed to 0, 5, 13, 20 or 30 ppt water salinities for 60 days; then blood samples were taken from all treatment for hormonal and enzymatic studies. All fish died at 30 ppt water salinity, during adaptation. The results showed that there was a tendency to triiodothyronine (T3) elevation along with water salinity levels, although the changes were not statistically significant (P>0.05). Increase in water salinity significantly increased serum thyroxine (T4), cortisol, alkaline phosphatase (ALP) and protease levels. Among the water salinities, 20 ppt led to a significant elevation in serum alanine aminotransferase (ALT) activity. There was no significant difference in serum glucose and aspartate aminotransferase (AST) levels in the fish reared at 5 and 13 ppt salinities; both treatments exhibited lower values compared to the 0 and 20 ppt salinities. Water salinity induced no significant changes in serum lipase activity. In conclusion, the results indicate that increase in water salinity causes elevation in cortisol and thyroid hormones, which are necessary for energy production and osmoregulation. Moreover, rainbow trout may face organ damage in saltwater, particularly at 20 ppt.