B-Myb deficiency boosts bortezomib-induced immunogenic cell death in colorectal cancer.

B-Myb has received considerable attention for its critical tumorigenic function of supporting DNA repair. However, its modulatory effects on chemotherapy and immunotherapy have rarely been reported in colorectal cancer. Bortezomib (BTZ) is a novel compound with chemotherapeutic and immunotherapeutic effects, but it fails to work in colorectal cancer with high B-Myb expression. The present study was designed to investigate whether B-Myb deletion in colorectal cancer could potentiate the immune efficacy of BTZ against colorectal cancer and to clarify the underlying mechanism. Stable B-Myb knockdown was induced in colorectal cancer cells, which increased apoptosis of the cancer cells relative to the control group in vitro and in vivo. We found that BTZ exhibited more favourable efficacy in B-Myb-defective colorectal cancer cells and tumor-bearing mice. BTZ treatment led to differential expression of genes enriched in the p53 signaling pathway promoted more powerful downstream DNA damage, and arrested cell cycle in B-Myb-defective colorectal cancer. In contrast, recovery of B-Myb in B-Myb-defective colorectal cancer cells abated BTZ-related DNA damage, cell cycle arrest, and anticancer efficacy. Moreover, BTZ promoted DNA damage-associated enhancement of immunogenicity, as indicated by potentiated expression of HMGB1 and HSP90 in B-Myb-defective cells, thereby driving M1 polarization of macrophages. Collectively, B-Myb deletion in colorectal cancer facilitates the immunogenic death of cancer cells, thereby further promoting the immune efficacy of BTZ by amplifying DNA damage. The present work provides an effective molecular target for colorectal cancer immunotherapy with BTZ.

Up-regulation of ABCG2 by MYBL2 deletion drives Chlorin e6-mediated photodynamic therapy resistance in colorectal cancer.

OBJECTIVE: Photodynamic therapy (PDT) may be an effective therapeutic strategy for colorectal cancer at an early stage. However, malignant cells' resistance to photodynamic agents can lead to treatment failure. MYBL2 (B-Myb) is an oncogene in colorectal carcinogenesis and development, for which little research has focused on its effect on drug resistance. MATERIALS AND METHODS: In the present work, a colorectal cancer cell line with a stable knockdown of MYBL2 (ShB-Myb) was constructed first. Chlorin e6 (Ce6) was utilized to induced PDT. The anti-cancer efficacy was measured by CCK-8, PI staining, and Western blots. The drug uptake of Ce6 was assayed by flow cytometry and confocal microscopy. The ROS generation was detected by the CellROX probe. DDSB and DNA damage were assayed through comet experiment and Western blots. The over-expression of MYBL2 was conducted by MYBL2 plasmid. RESULTS: The findings indicated that the viability of ShB-Myb treated with Ce6-PDT was not decreased compared to control SW480 cells (ShNC), which were resistant to PDT. Further investigation revealed reduced photosensitizer enrichment and mitigated oxidative DNA damage in colorectal cancer cells with depressed MYBL2. It turned out that SW480 cells knocking down MYBL2 showed phosphorylation of NF-κB and led to up-regulation of ABCG2 expression thereupon. When MYBL2 was replenished back in MYBL2-deficient colorectal cancer cells, phosphorylation of NF-κB was blocked and ABCG2 expression up-regulation was suppressed. Additionally, replenishment of MYBL2 also increased the enrichment of Ce6 and the efficacy of PDT. CONCLUSION: In summary, MYBL2 absence in colorectal cancer contributes to drug resistance by activating NF-κB to up-regulate ABCG2 and thereby leading to photosensitizer Ce6 efflux. This study provides a novel theoretical basis and strategy for how to effectively improve the anti-tumor efficacy of PDT.

The sarcopenia index is an effective predictor for malnutrition in patients with liver cirrhosis.

AIM: Reliable and valid predictors of malnutrition in patients with cirrhosis remain scarce, especially easily accessible blood indicators. Thus, this study aimed to investigate the validity of the sarcopenia index (serum creatinine/serum cystatin C × 100) as a tool in assessing the nutritional status of patients with cirrhosis. METHODS: This prospective cohort study included 109 patients with cirrhosis who were hospitalised in Renmin Hospital of Wuhan University from August 2020 to June 2021. Malnutrition was diagnosed by the Global Leadership Initiative on Malnutrition criteria. Multivariable logistic regression was used to examine the relationship between sarcopenia index and malnutrition. The area under the receiver operating characteristic curve was used to evaluate the diagnostic performance of sarcopenia index. By contrast, we evaluated the subjective global assessment and traditional nutrition-related indicators. RESULTS: Of the 109 included patients, 71 (65.1%) were diagnosed with malnutrition. The sarcopenia index was significantly lower in malnourished patients (56.39 ± 15.23) compared with well-nourished patients (74.95 ± 13.18, p < 0.001). In addition, the sarcopenia index was independently correlated with malnutrition (p < 0.001). The sarcopenia index was a good tool to predict malnutrition (area under curve = 0.833), which performed better than the subjective global assessment (area under curve = 0.782) and cholinesterase (area under curve = 0.812). A low sarcopenia index indicated longer hospital stay and higher risk of 90-day re-hospitalisation. CONCLUSION: Malnutrition is highly prevalent in this population. The sarcopenia index seems to be a good predictor in nutritional assessment of patients with cirrhosis.

Inhibition of macrophage migration inhibitory factor prevents thyroid dysfunction in pregnant rats with acute pancreatitis.

Acute pancreatitis during pregnancy (APIP) rarely occurs but may lead to preterm delivery and be associated with high fetal mortality. Macrophage migration inhibitory factor (MIF) participates in various inflammatory diseases as a pro-inflammatory cytokine. In this study, we aimed to explore the effects of (S, R)-3-(4-hydroxyphenyl)-4, 5dihydro-5-isoxazole acetic methyl ester (ISO-1), an inhibitor of MIF, on maternal thyroid injury associated with APIP and its potential mechanisms in a pregnant rat model. APIP model was induced by retrograde injection of sodium taurocholate. ISO-1 was injected intraperitoneally 30 min before model establishment. The severity of pancreatitis was assessed by levels of tumor necrosis factor (TNF)­α, interleukin (IL)­1ß, IL-6 of maternal serum as well as histopathological score. Thyroid injury was determined by free triiodothyronine (FT3), free tetraiodothyronine (FT4) and thyroid histopathological score. Levels of MIF in maternal serum and the expression of MIF, CD68, CD3 and intercellular cell adhesion molecule-1 (ICAM-1) as well as oxidative stress status in maternal thyroid tissues were detected. Ultrastructure of maternal thyroid tissues was observed by transmission electron microscope. Thyroid injuries occurred in APIP and the lesions were attenuated with the pretreatment of ISO-1. Moreover, ISO-1 reduced the expression of MIF, attenuated the activations of CD68, CD3, ICAM-1 while improved oxidative stress status in maternal thyroid. Our research suggested a protective role of ISO-1 on thyroid injury and endocrine disorder during APIP, which may be associated with the inhibition of biological functions of MIF.

[Effect of HRT on Denitrifying Phosphorus and Nitrogen Removal in Modified A2/O-BAF].

The effect of hydraulic retention time (HRT) on denitrifying phosphorus and nitrogen removal in a modified two sludge A2/O-BAF system was studied. The influent COD, NH4+-N, and TP were 189.6, 60.4, and 5.1 mg·L-1, respectively. When HRT was 9, 8, 7, and 6 h, the average effluent COD was less than 42 mg·L-1. The average effluent NH4+-N levels were 2.4, 2.8, 3.3, and 6.5 mg·L-1, respectively. The average effluent TP values were 0.3, 0.4, 0.7, and 0.8 mg·L-1, respectively. The ratio of the denitrifying phosphorus accumulation organisms (DPAOs/PAOs) in the system of anoxic zone was reduced from 76.8% to 48.8%. When HRT was 8 h, the ratio of denitrifying phosphorus to nitrogen (ΔPO43-/ΔNO3--N) was increased by 37.5% by a mathematical statistics method. The ΔPO43-/ΔNO3--N in the anoxic zone was 1.24 (the theoretical value is 1.41). At this time, the effect of denitrifying phosphorus to nitrogen was the best. The SVI value was lower than 100 mL·g-1 throughout the experiment, and the MLVSS/MLSS gradually decreased from 0.74 to 0.63, indicating that the sludge activity was reduced.

High-Fat Diet Aggravates Acute Pancreatitis via TLR4-Mediated Necroptosis and Inflammation in Rats.

High-fat diet (HFD) often increases oxidative stress and enhances inflammatory status in the body. Toll-like receptor 4 (TLR4) is widely expressed in the pancreatic tissues and plays an important role in pancreatitis. This study is aimed at investigating the effect of HFD on acute pancreatitis (AP) and the role of TLR4-mediated necroptosis and inflammation in this disease. Weight-matched rats were allocated for an 8-week feeding on the standard chow diet (SCD) or HFD, and then, the AP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. Rats were sacrificed at an indicated time point after modeling. Additionally, inhibition of TLR4 signaling by TAK-242 in HFD rats with AP was conducted in vivo. The results showed that the levels of serum free fatty acid (FFA) in HFD rats were higher than those in SCD rats. Moreover, HFD rats were more vulnerable to AP injury than SCD rats, as indicated by more serious pathological damage and much higher pancreatic malondialdehyde (MDA) and lipid peroxidation (LPO) levels as well as lower pancreatic superoxide dismutase (SOD) activities and reduced glutathione (GSH) contents and more intense infiltration of MPO-positive neutrophils and CD68-positive macrophages. In addition, HFD markedly increased the expressions of TLR4 and necroptosis marker (RIP3) and aggravated the activation of NF-κB p65 and the expression of TNF-α in the pancreas of AP rats at indicated time points. However, TLR4 inhibition significantly attenuated the structural and functional damage of the pancreas induced by AP in HFD rats, as indicated by improvement of the above indexes. Taken together, these findings suggest that HFD exacerbated the extent and severity of AP via oxidative stress, inflammatory response, and necroptosis. Inhibition of TLR4 signaling by TAK-242 alleviated oxidative stress and decreased inflammatory reaction and necroptosis, exerting a protective effect during AP in HFD rats.

[Short-cut Nitrification Start-up and Optimization of Operating Conditions Under Different Control Strategies].

Low C/N domestic sewage was treated in a SBR. With an operating temperature of (25±0.5)℃, NO2--N accumulation rates reached 96.79%, 98.80%, and 98.78% after 69, 63, and 58 cycles, respectively. In each case, alternating modes of hypoxia/aerobic (four times), aerobic/anoxic (five times), and aerobic/anoxic (four times) were applied, respectively, with an alternating time of 30 min. At the same temperature, when the aerobic/anoxic time ratios were 30 min:30 min, 40 min:20 min, and 30 min:60 min, and the single-cycle alternating times were 5, 3, and 5, respectively, stable NO2--N accumulation rates reached 98.81%, 97.71%, and 94.64% after 63, 73, and 78 cycles, respectively. The activity of AOB was 96.30, 99.27, and 102.26, respectively. Simultaneous nitrification and denitrification occurred under the three aerobic/anoxic time ratios. The total amounts of nitrogen removed by synchronous nitrification and denitrification were 29.89, 28.77, and 29.78 mg·L-1. When temperatures were adjusted to 18, 25, and 30℃, and when the aerobic/anoxic time ratio was 30 min:30 min, the NO2--N accumulation rates were 99.58%, 99.21%, and 95.93% after 90, 64, and 61 cycles, respectively. The activity of the sludge (f) peaked when after 64, 40, and 48 cycles, while the sludge-settling performance was good.

Double-edge Role of B Cells in Tumor Immunity: Potential Molecular Mechanism.

B cells are a heterogeneous population, which have distinct functions of antigen presentation, activating T cells, and secreting antibodies, cytokines as well as protease. It is supposed that the balance among these B cells subpopulation (resting B cells, activated B cells, Bregs, and other differentiated B cells) will determine the ultimate role of B cells in tumor immunity. There has been increasing evidence supporting opposite roles of B cells in tumor immunity, though there are no general acceptable phenotypes for them. Recent years, a new designated subset of B cells identified as Bregs has emerged from immunosuppressive and/or regulatory functions in tumor immune responses. Therefore, transferring activated B cells would be possible to become a promising strategy against tumor via conquering the immunosuppressive status of B cells in future. Understanding the potential mechanism of double-edge role of B cells will help researchers utilize activated B cells to improve their anti-tumor response. Moreover, the molecular pathways related to B cell differentiation are involved in its tumor-promoting effect, such as NF-κB, STAT3, BTK. So, we review the molecular and signaling pathway mechanisms of B cells involved in both tumor-promoting and tumor-suppressive immunity, in order to help researchers optimize B cells to fight cancer better.

Apocynin alleviates lung injury by suppressing NLRP3 inflammasome activation and NF-κB signaling in acute pancreatitis.

Mounting evidence has demonstrated that acute pancreatitis (AP) is one of the causes of multiple organ damage. NADPH (nicotinamide adenine dinucleotide phosphate) act as a substrate of NADPH oxidase (NOX) to generate reactive oxygen species (ROS), but the role NADPH oxidase signaling pathway plays in AP-induced acute lung injury remains unclear. Apocynin, an inhibitor of NOX, is highly effective in suppressing the production of ROS. Here, we used rat model of severe acute pancreatitis (SAP) to explore whether the NOX inhibitor apocynin produced protective effects in against SAP-induced lung injury via inhibition of inflammation and oxidation. We observed that apocynin significantly attenuated severe acute pancreatitis-induced increase of NOX2, NOX4 and ROS expressions in lung tissues. In addition, the phosphorylation and degradation of IκBα, and the nuclear localization of NF-κB p65 in SAP-induced lung injury were also inhibited after using apocynin. Simultaneously, down-regulation of NOX suppressed the levels of inflammasome proteins including NLRP3, ASC, pro-Caspase-1 and cleaved-Caspase-1 in the lung. Serum levels of TNF-α, interleukin (IL)-1ß and IL-6 were also reduced. Our findings suggest that beyond anti-oxidative effects, apocynin may also have anti-inflammatory effects by suppressing NLRP3 inflammasome activation and NF-κB signaling in acute pancreatitis. Therefore, apocynin may have therapeutic potential in the treatment of SAP and SAP-induced lung injury.

High-Fat Diet Aggravates the Intestinal Barrier Injury via TLR4-RIP3 Pathway in a Rat Model of Severe Acute Pancreatitis.

OBJECTIVE: For patients with severe acute pancreatitis (SAP), a high body mass index (BMI) increases the possibility of infection derived from the intestine. In this study, we evaluate whether TAK242 can alleviate severe acute pancreatitis-associated injury of intestinal barrier in high-fat diet-fed rats. METHODS: A SAP model was established by retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct. Thirty Sprague-Dawley (SD) adult rats were randomly divided into five groups: standard rat chow (SRC) normal (SN), SRC SAP (SAP), high-fat diet normal (HN), HFD SAP (HSAP), and TLR4 inhibitor pretreatment HFD SAP (HAPT) groups. Intraperitoneal injection of 3 mg/kg TAK242 was administered 30 minutes before SAP model establishment in the HAPT group. Rats were sacrificed 12 hours after SAP modeling, followed by blood and pancreatic and distal ileum tissue collection for further analyses. Changes in the pathology responses of the rats in each group were assessed. RESULT: Analyses of serum amylase, lipase, cholesterol, triglyceride, IL-1ß, IL-6, DAO, and serum endotoxin as well as tight junction protein expression including zonula occluden-1 and occludin indicated that high-fat diet aggravated SAP-induced intestinal barrier injury via increasing inflammatory response. In addition, the level of necroptosis was significantly higher in the SAP group compared with the SN group while the HSAP group exhibited more necroptosis compared with the SAP group, indicating the important role of necroptosis in pancreatitis-associated gut injury and illustrating that high-fat diet aggravated necroptosis of the ileum. Pretreatment with TLR4 inhibitor significantly alleviated inflammatory response and reduced necroptosis and level of oxidative stress while improving intestinal barrier function. CONCLUSION: High-fat diet aggravated SAP-induced intestinal barrier injury via inflammatory reactions, necroptosis, and oxidative stress. Inhibition of TLR4 by TAK242 reduced inflammation, alleviated necroptosis, and lowered the level of oxidative stress and then protected the intestinal barrier dysfunction from SAP in high-fat diet-fed rats.

Macrophage Migration Inhibitor Promoted the Intrahepatic Bile Duct Injury in Rats with Severe Acute Pancreatitis.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is involved in many acute and chronic inflammatory diseases. However, its role in intrahepatic bile duct (IBD) cell damage associated with severe acute pancreatitis (SAP) remains unclear. AIMS: This study was aimed to identify the role of MIF and its underlying mechanisms in SAP complicated by IBD cell damage. METHODS: Forty-eight specific-pathogen-free male Wistar rats were randomly divided into four groups (N = 12): a sham operation group (SO group) and three SAP model groups (SAP-3h, SAP-6h, and SAP-12h). Immunohistochemistry was used to detect the expression of MIF and P38 in IBD cells. MIF mRNA expression in IBD cells was observed using real-time fluorescent quantitative polymerase chain reaction (real-time PCR). In addition, Western blotting was performed to detect the protein expression of P38, phosphorylated P38 (P-P38), nuclear factor-κB (NF-κB p65), and tumor necrosis factor alpha (TNF-α). Enzyme-linked immunosorbent assays were used to analyze the levels of TNF-α, IL-1ß, and IL-6 in the IBD of rats. RESULTS: Compared with the SO group, the expression of MIF in the IBD was significantly upregulated both at mRNA and at protein levels in the SAP group. Besides, the protein expression levels of P38, P-P38, NF-κB, p65, TNF-α, IL-1ß, and IL-6 in the IBD in rats were also significantly increased in the SAP group and the levels increased gradually as acute pancreatitis progressed (all P < 0.05). CONCLUSIONS: MIF may promote the IBD injury and inflammatory reaction in SAP via activating the P38-MAPK and NF-κB signaling pathways.

Hydrogen-Rich Saline Attenuates Acute Hepatic Injury in Acute Necrotizing Pancreatitis by Inhibiting Inflammation and Apoptosis, Involving JNK and p38 Mitogen-Activated Protein Kinase-dependent Reactive Oxygen Species.

OBJECTIVES: The objective of this study was to study the role of hydrogen-rich saline (HRS) on acute hepatic injury (AHI) in acute necrotizing pancreatitis (ANP). METHODS: Rats were used for this study and an ANP model was induced by injecting 5% sodium taurocholate into the biliary-pancreatic duct. Experiments were performed in 3 groups: sham, ANP, and ANP + HRS (HRS). Animals were killed at 3, 12, and 24 hours after operation, and then blood and tissue samples were harvested. Various physiological, histological, and cellular and molecular parameters were analyzed. RESULTS: Analyses of serum, lipase, alanine transaminase, and aspartate aminotransferase indicated that ANP-induced AHI model was established successfully and HRS attenuated hepatic dysfunction. Hepatic superoxide dismutase and malondialdehyde levels showed HRS against oxidative stress. Cellular and molecular analyses including p-p38, p-JNK, p-ERK, and caspase-3, caspase-9, NF-κB, and TNF-α in hepatic tissues revealed that HRS attenuated ANP-induced AHI by inhibiting apoptosis and phosphorylation of JNK and p38, as well as NF-κB activation. CONCLUSIONS: Hydrogen-rich saline plays a protective role in ANP-induced AHI through inhibiting inflammation and apoptosis, involving JNK and p38 MAPK-dependent reactive oxygen species.

Mitogen-Activated Protein Kinases Are Activated in Placental Injury in Rat Model of Acute Pancreatitis in Pregnancy.

OBJECTIVES: To establish a rat model of acute pancreatitis in pregnancy (APIP) and evaluate its general presentations, assess placental injury, and discuss possible mechanisms. METHODS: The APIP rat model was induced by sodium taurocholate in Sprague-Dawley rats of later gestation. Normal and sham-operated (SO) rats in later gestation were set as controls, 3 time points were set in SO and APIP groups to determine optimal modeling time. Histological changes of pancreas and placenta were assessed. Placental injury was determined by immunohistochemistry stain of caspase-3. Serum levels of amylase, lipase, and Ca; proinflammatory cytokines as tumor necrosis factor-α, interleukin-1ß (IL-1ß), IL-6, and anti-inflammatory cytokine IL-10 by enzyme-linked immunosorbent assay; mitogen-activated protein kinases and their phosphorylated forms by Western blotting. RESULTS: Pancreatic necrotizing and placental injury occurred in time-dependent patterns. Serum levels of amylase and lipase significantly increased but Ca decreased; tumor necrosis factor-α, IL-1ß, IL-6, and IL-10 were all increased in the APIP group; c-Jun N-terminal kinase, p38, and ERK1/2 were activated but with different distributing patterns in the placenta. CONCLUSIONS: Placental injury is involved in the rat model of APIP, and a modeling time of 6 hours is optimal and conducive to further studies; c-Jun N-terminal kinase and p38 may play important roles in placental injury during APIP.

Hydrogen-rich saline attenuates acute renal injury in sodium taurocholate-induced severe acute pancreatitis by inhibiting ROS and NF-κB pathway.

Hydrogen (H2), a new antioxidant, was reported to reduce (•)OH and ONOO(-) selectively and inhibit certain proinflammatory mediators to product, without disturbing metabolic redox reactions or ROS involved in cell signaling. We herein aim to explore its protective effects on acute renal injury in sodium taurocholate-induced acute pancreatitis and its possible mechanisms. Rats were injected with hydrogen-rich saline (HRS group) or normal saline (SO and SAP group) through tail intravenously (6 mL/kg) and compensated subcutaneously (20 mL/kg) after successful modeling. Results showed that hydrogen-rich saline attenuated the following: (1) serum Cr and BUN, (2) pancreatic and renal pathological injuries, (3) renal MDA, (4) renal MPO, (5) serum IL-1ß, IL-6, and renal TNF-α, HMGB1, and (6) tyrosine nitration, IκB degradation, and NF-κB activation in renal tissues. In addition, it increased the level of IL-10 and SOD activity in renal tissues. These results proved that hydrogen-rich saline attenuates acute renal injury in sodium taurocholate-induced acute pancreatitis, presumably because of its detoxification activity against excessive ROS, and inhibits the activation of NF-κB by affecting IκB nitration and degradation. Our findings highlight the potential value of hydrogen-rich saline as a new therapeutic method on acute renal injury in severe acute pancreatitis clinically.

Protective effects of daphnetin on sodium taurocholate­induced severe acute pancreatitis in rats.

Severe acute pancreatitis (SAP) is the sudden onset of pancreatic inflammation, which is characterized by edema, acinar cell necrosis, hemorrhage and severe inflammation of the pancreas and is associated with a high mortality rate. Daphnetin has been shown to alleviate organ injury in a variety of preclinical animal models of coagulation disorders. The aim of the present study was to investigate the protective effects of daphnetin on severe acute pancreatitis in a rat model. Severe acute pancreatitis in the rat model was induced by retrograde infusion of 5% sodium taurocholate (1 ml/kg) into the bile-pancreatic duct. Daphnetin (4 mg/kg) was administered intraperitoneally at 30 min prior to the infusion of sodium taurocholate. The severity of pancreatitis was evaluated by various analyses of serum amylase and lipase, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels, myeloperoxidase (MPO) activity and malondialdehyde (MDA) content, as well as by histological grading. The levels of TNF-α and IL-1ß in the serum were measured by ELISA. The results revealed that the daphnetin-treated SAP rat group (SAP-D) exhibited a lower pathological score of the pancreas compared with the SAP group (SAP). Further analyses demonstrated that the SAP-D group had lower levels of serum amylase, lipase and pro-inflammatory cytokines, including TNF-α and IL-1ß, and a decreased MPO activity and MDA content 3, 6 and 12 h subsequent to the infusion of sodium taurocholate compared with the SAP group (SAP). These findings indicated that daphnetin exerted a protective function in the SAP rat model. Therefore, daphnetin may be considered as a potential compound for the therapy and prevention of acute pancreatitis.

Rosiglitazone attenuates the severity of hyperlipidemic severe acute pancreatitis in rats.

Peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand regulates adipocyte differentiation and insulin sensitivity, and exerts antihyperlipidemic and anti-inflammatory effects. However, the mechanisms by which PPAR-γ ligands affect hyperlipidemia with severe acute pancreatitis (SAP) have not been fully elucidated. The present study investigated the effects of rosiglitazone, a PPAR-γ ligand, on hyperlipidemia with SAP in a rat model. The hyperlipidemia was induced with a high-fat diet and SAP was induced by the administration of sodium taurocholate (TCA). The hyperlipidemia was shown to aggravate the severity of the sodium taurocholate-induced SAP. However, rosiglitazone demonstrated significant antihyperlipidemic and anti-inflammatory effects in the rats with high-lipid diet-induced hyperlipidemia and SAP.

[Expression of PARP/NF-κB and intervention effect of 5-AIQ/PDTC in SAP rats with adrenal damage].

OBJECTIVE: To explore the expression of poly (ADP-ribose) polymerase/nuclear factor-κB (PARP/NF-κB) and intervention effect of 5-aminoisoquinolinone/pyrrolidine dithiocarbamate (5-AIQ/PDTC) in severe acute pancreatitis (SAP) rats with adrenal damage. METHODS: The primarily cultured adrenocortical cells were quantitatively divided into control group (SO), pancreatitis group (SAP), PDTC drug control group (SO+PDTC), PDTC intervention group (SAP+PDTC), 5-AIQ drug control group (SO+ 5-AIQ) and 5-AIQ intervention group (SAP+5-AIQ). The SAP and 2 intervention groups were stimulated with the sera of SAP rats. Then corresponding drugs were added and culture continued for 12 hours. The corticosterone levels and PARP/NF-κB expression were observed for each group. RESULTS: Adrenal cells in vitro cultured were round or oval, had secretory granules and could be stained by 3ß-hydroxysteroid dehydrogenase antibody. The adherence rate was 60% after 48-hour culturing. The corticosterone level of SAP group was significantly lower than that of SO group [ (216.4 ± 15.7) vs (294.8 ± 16.3) µg/L, P < 0.05]. The 2 intervention groups were (258.6 ± 19.0) and (264.3 ± 18.2) µg/L respectively. These two values were higher than those of SAP group (P < 0.05), but lower than those of SO group (P < 0.05). With regards to the expression of PARP-1, the SAP and PDTC intervention groups were higher than SO group while 5-AIQ intervention group was significantly lower than SAP and PDTC intervention groups, but higher than SO and drug control groups. The expression of NF-κB in SAP group was higher than that in SO group. Two intervention groups were lower than SAP group, but higher than SO and drug control groups. CONCLUSION: The pathway of PARP/NF-κB participates in adrenal damage of SAP rats. To a certain extent, the uses of 5-AIQ and PDTC may alleviate adrenal damage.