PKM2 functions as a histidine kinase to phosphorylate PGAM1 and increase glycolysis shunts in cancer.

Phosphoglycerate mutase 1 (PGAM1) is a key node enzyme that diverts the metabolic reactions from glycolysis into its shunts to support macromolecule biosynthesis for rapid and sustainable cell proliferation. It is prevalent that PGAM1 activity is upregulated in various tumors; however, the underlying mechanism remains unclear. Here, we unveil that pyruvate kinase M2 (PKM2) moonlights as a histidine kinase in a phosphoenolpyruvate (PEP)-dependent manner to catalyze PGAM1 H11 phosphorylation, that is essential for PGAM1 activity. Moreover, monomeric and dimeric but not tetrameric PKM2 are efficient to phosphorylate and activate PGAM1. In response to epidermal growth factor signaling, Src-catalyzed PGAM1 Y119 phosphorylation is a prerequisite for PKM2 binding and the subsequent PGAM1 H11 phosphorylation, which constitutes a discrepancy between tumor and normal cells. A PGAM1-derived pY119-containing cell-permeable peptide or Y119 mutation disrupts the interaction of PGAM1 with PKM2 and PGAM1 H11 phosphorylation, dampening the glycolysis shunts and tumor growth. Together, these results identify a function of PKM2 as a histidine kinase, and illustrate the importance of enzyme crosstalk as a regulatory mode during metabolic reprogramming and tumorigenesis.

An alkali-extracted neutral heteropolysaccharide from Phellinus nigricans used as an immunopotentiator in immunosuppressed mice by activating macrophages.

A neutral heteropolysaccharide (PNANb) was isolated with alkali (0.1 M NaOH) from mycelia of Phellinus nigricans, and the structure, immunostimulating activity and some of the underlying molecular mechanisms of action of PNANb were explored in the current study. PNANb (14.95 kDa) predominantly consisted of Gal, Glc, and Man with minor Fuc. GC-MS and NMR analyses indicated that the backbone of PNANb was mainly composed of 6-α-Galp, 2,6-α-Galp with minor 3,6-ß-Glcp, which was substituted with complex side chains at C-2 of 2,6-α-Galp and C-3 of 3,6-ß-Glcp. Notably, PNANb (50 or 100 mg/kg) possessed immunoprotective effects in cyclophosphamide (Cy)-induced immunosuppressed C57BL/6 mice, which was supported by evidence including the enhancement of spleen and thymus indices, levels of serum immunoglobulins (IgG, IgM) and cytokines (IFN-γ, IL-2, IL-4, IL-10), and macrophage activity. However, the immunostimulation effects of PNANb were decreased when macrophages were depleted, underscoring the essential role of macrophages in the beneficial effects of PNANb in Cy-induced immunosuppressed mice. Further investigations in vitro indicated that PNANb activated macrophages through MAPK/NF-κB signaling pathways mediated by Toll-like receptor 4. Therefore, PNANb can serve as a prospective immunopotentiator in immunosuppression.

Effects of Medium Additives on the Mycelial Growth and Polysaccharide Biosynthesis in Submerged Culture of Bjerkandera fumosa.

Medium additives have been shown to affect the synthesis of active products in fungi. This study investigated the effects of corn stalk, poplar sawdust, Tween-80, and oleic acid on mycelial biomass and physicochemical properties, as well as the bioactivity of polysaccharides, including exopolysaccharides (EPS) and intracellular polysaccharides (IPS), in the submerged culture of Bjerkandera fumosa. Results showed that the addition of corn stalk or poplar sawdust increased the production of EPS but decreased the production of IPS; Tween-80 had less effect on the production of EPS and IPS; and oleic acid stimulated polysaccharide production significantly. Polysaccharide property analysis showed that the addition of corn stalk or poplar sawdust promoted the production of high-molecular-weight components in polysaccharides and changed the monosaccharide composition of polysaccharides, as well as increased the mannose, glucuronic acid, and xylose contents of IPS. Tween-80 and oleic acid also changed the molecular weight distribution of polysaccharides but only slightly affected the composition of monosaccharides. The bioactivity assay indicated that the polysaccharides obtained by adding corn stalk possessed high hydroxyl radical scavenging and antitumor activities. The effect of poplar sawdust was slightly weaker than that of corn stalk. EPS and IPS obtained from a culture with Tween-80 and oleic acid possessed low antioxidant activity. Moreover, their antitumor activity was improved and lost, respectively. The results obtained in this work are useful for improving the understanding of the optimization and regulation of bioactive polysaccharide production in the submerged culture of B. fumosa.

Irradiation effects on characteristics and ethanol fermentation of maize starch.

Maize starch was irradiated by a Co60 irradiator with different doses. The morphology and physicochemical properties of native and irradiated starches were investigated. Scanning electron microscopy showed that the shape and size of starch granules did not change after irradiation. However, the irradiated starch granules were easily destroyed by dissolution. Irradiation also caused the change of starch color, the decrease in the pH value, light transmittance, stability index, degree of polymerization, total sugar content, and the increase in the swelling index and the reducing sugar content. In this study, irradiated maize starch was also used as material for ethanol fermentation to investigate its potential as a pretreatment method. Results showed that the ethanol yield of cooked and raw starch fermentation using irradiated starch increased by 20.41 % and 5.18 %, respectively, and the ethanol concentration increased by 3 % and 2 %. This finding indicated that irradiation effectively improved the utilization rate of maize starch, making it an effective pretreatment method for ethanol fermentation.

[Application and progress of data mining in study of compatibility law of traditional Chinese medicine].

Data mining is an important method to obtain the key information from a large amount of data, and it is widely applied in the research on the modernization of traditional Chinese medicine(TCM). The compatibility law of herbs is a key issue in the research of TCM prescriptions. This reflects the flexibility and effectiveness of TCM prescriptions, and it is also a crucial link to the development of TCM modernization. Therefore, it is the core purpose of the research on TCM prescriptions to find the compatibility law of herbs and clarify the scientific connotation. Data mining, as an effective method and an important approach, has formed a standardized system in the research of compatibility law of herbs, which can reveal the relationship between different Chinese herbs and summarize the internal rules in compatibility. Two hundred and twenty two effective papers were sorted out and categorized in this article. The results showed that data mining was mainly applied in finding the core Chinese herb pairs, summarizing the utility and attributes of TCM prescriptions, revealing the relationship between prescriptions, Chinese herbs and syndromes, finding the optimal dose of Chinese herbs, and producing the new prescriptions. The problems of data mining in research of herbs compatibility rules were summarized, and its development and trend in current researches were discussed in this article to provide useful references for the in-depth study of data mining in the compatibility law of Chinese herbs.

Application of an extreme learning machine network with particle swarm optimization in syndrome classification of primary liver cancer.

OBJECTIVE: By optimizing the extreme learning machine network with particle swarm optimization, we established a syndrome classification and prediction model for primary liver cancer (PLC), classified and predicted the syndrome diagnosis of medical record data for PLC and compared and analyzed the prediction results with different algorithms and the clinical diagnosis results. This paper provides modern technical support for clinical diagnosis and treatment, and improves the objectivity, accuracy and rigor of the classification of traditional Chinese medicine (TCM) syndromes. METHODS: From three top-level TCM hospitals in Nanchang, 10,602 electronic medical records from patients with PLC were collected, dating from January 2009 to May 2020. We removed the electronic medical records of 542 cases of syndromes and adopted the cross-validation method in the remaining 10,060 electronic medical records, which were randomly divided into a training set and a test set. Based on fuzzy mathematics theory, we quantified the syndrome-related factors of TCM symptoms and signs, and information from the TCM four diagnostic methods. Next, using an extreme learning machine network with particle swarm optimization, we constructed a neural network syndrome classification and prediction model that used "TCM symptoms + signs + tongue diagnosis information + pulse diagnosis information" as input, and PLC syndrome as output. This approach was used to mine the nonlinear relationship between clinical data in electronic medical records and different syndrome types. The accuracy rate of classification was used to compare this model to other machine learning classification models. RESULTS: The classification accuracy rate of the model developed here was 86.26%. The classification accuracy rates of models using support vector machine and Bayesian networks were 82.79% and 85.84%, respectively. The classification accuracy rates of the models for all syndromes in this paper were between 82.15% and 93.82%. CONCLUSION: Compared with the case of data processed using traditional binary inputs, the experiment shows that the medical record data processed by fuzzy mathematics was more accurate, and closer to clinical findings. In addition, the model developed here was more refined, more accurate, and quicker than other classification models. This model provides reliable diagnosis for clinical treatment of PLC and a method to study of the rules of syndrome differentiation and treatment in TCM.

Biodegradation of polyhydroxybutyrate by Pseudomonas sp. DSDY0501 and purification and characterization of polyhydroxybutyrate depolymerase.

Strain DSDY0501 with polyhydroxybutyrate (PHB)-degrading ability was isolated from activated sludge. The morphological, physiological, and biochemical properties of the strain and phylogenetic analysis indicated that the strain belongs to Pseudomonas sp. The strain used PHB as the sole carbon source and degraded PHB films completely in 21 h in liquid culture. An extracellular PHB depolymerase was purified from the supernatant of the culture by ultrafiltration and Sephacryl S-200 gel filtration. The specific activity of the purified enzyme increased 24.2-fold, and the recovery yield was 16.61%. Extracellular PHB depolymerase, a monomeric enzyme with a molecular weight of approximately 57.9 kDa, showed optimum activity at 60 °C and pH 9.0, and was stable in the temperature range of 10-60 °C and a pH range of 6.0-10.0. The secondary structure of the enzyme contained approximately 60% α-helix and 40% ß-pleated sheet according to the circular dichroism spectrum. Mass spectrum analysis showed that the main degradation product of the enzyme was PHB monomer, indicating the exo-type action of this PHB depolymerase.

[Utilization and cost of outpatient care and their influencing factors among middle and aged peasant-workers in China].

OBJECTIVE: To examine the utilization and cost of outpatient care and their influencing factors among middle and aged peasant-workers in China. METHODS: The data of China Health and Retirement Longitudinal Study (CHARLS) collected in 2011-2012 were used and the data on peasant-workers aged 45 years and older were analyzed with Two-part Model. RESULTS: The four-week outpatient rate of middle and aged peasant-workers was 13.7% (407/2 974). The determinants of the rate included gender, marital status, economic level, household size, the place of insurance enrollment, self-assessed health and having or having no chronic diseases. The average outpatient cost was (400.3±56.7) yuan (RMB) and the median was 138.0 yuan. Multivariate analyses showed that outpatient costs were higher for those males who lived in Eastern China and worked at the same place with insurance enrollment, with fair to bad self-assessed health and chronic diseases. CONCLUSION: Allowing higher flexibility for migrants to transfer the new rural cooperative medical system(NCMS) between rural and urban areas and thus making reimbursement for medical services provided by undesignated providers received immediately could increase the use of outpatient services.

Methylene Blue Reduces Acute Cerebral Ischemic Injury via the Induction of Mitophagy.

The treatment of stroke is limited by a short therapeutic window and a lack of effective clinical drugs. Methylene blue (MB) has been used in laboratories and clinics since the 1890s. Few studies have reported the neuroprotective role of MB in cerebral ischemia-reperfusion injury. However, whether and how MB protects against acute cerebral ischemia (ACI) injury was unclear. In this study, we investigated the effect of MB on this injury and revealed that MB protected against ACI injury by augmenting mitophagy. Using a rat middle cerebral artery occlusion (MCAO) model, we demonstrated that MB improved neurological function and reduced the infarct volume and necrosis after ACI injury. These improvements depended on the effect of MB on mitochondrial structure and function. ACI caused the disorder and disintegration of mitochondrial structure, while MB ameliorated the destruction of mitochondria. In addition, mitophagy was inhibited at 24 h after stroke and MB augmented mitophagy. In an oxygen-glucose deprivation (OGD) model in vitro, we further revealed that the elevation of mitochondrial membrane potential (MMP) by MB under OGD conditions mediated the augmented mitophagy. In contrast, exacerbating the decline of MMP during OGD abolished the MB-induced activation of mitophagy. Taken together, MB promotes mitophagy by maintaining the MMP at a relatively high level, which contributes to a decrease in necrosis and an improvement in neurological function, thereby protecting against ACI injury.

Percolation of Phase-Separating Polymer Mixtures.

We study the percolation problem in a binary phase-separating polymer mixture. By well-designed experiments, we can delineate the percolation line on the phase diagram with sufficient accuracy. Our experiments show that the percolation thresholds start from the random percolation limit (Φ âˆ¼ 0.15) located near spinodal point at T → Tc and then converge toward the geometric coalescence limit (Φ âˆ¼ 0.36) with an increase in the quench depth. This apparent percolation difficulty comes about largely from the Rayleigh instability accompanied by large-amplitude, short-wavelength fluctuations during the spinodal decomposition at deeper quench depth. As a result, the broken "rigid" domains tend to pack closely, and the so-called droplet spinodal decomposition occurs. On the other hand, we observe that, between the selectively attractive walls, the surface-drying percolating phase will break up into droplets prematurely, thereby shifting its percolation line rather considerably. To our knowledge, such an effect is not yet predicted by theory or simulation.

Enhanced hypoxia-inducible factor (HIF)-1α stability induced by 5-hydroxymethyl-2-furfural (5-HMF) contributes to protection against hypoxia.

We first reported the role of 5-hydroxymethyl-2-furfural (5-HMF) against hypoxia. Here, we studied the mechanism by using oxygen-dependent degradation domain (ODD)-Luc mice, which are a useful model to probe the stabilization of hypoxia-inducible factor 1α (HIF-1α). Compared with three other compounds that have been reported to have a role in stabilizing HIF-1α, 5-HMF caused stronger bioluminescence, which is indicative of HIF-1α stability in the brain and kidney of ODD-Luc mice. We further demonstrated that the HIF-1α protein accumulated in response to 5-HMF in the brains and kidneys of these mice, as well as in PC12 cells. Additionally, 5-HMF promoted the nuclear translocation of HIF-1α and the transcriptional activity of HIF-1, which was evaluated by detecting vascular endothelial growth factor (VEGF ) mRNA expression. These results suggest that 5-HMF stabilized HIF-1α and increased its activity. Considering the role of proline hydroxylases (PHDs) in negatively regulating HIF-1α stability, we explored whether 5-HMF interacts with the substrates and cofactors of PHDs, such as 2-oxoglutarate (2-OG), Fe(2+) and vitamin C (VC), which affects the activity of PHDs. The result revealed that 5-HMF did not interact with Fe(2+) or 2-OG but interacted with VC. This interaction was confirmed by subsequent experiments, in which 5-HMF entered into cells and reduced the VC content. The enhanced stability of HIF-1α by 5-HMF was reversed by VC supplementation, and the improved survival of mice caused by 5-HMF under hypoxia was abrogated by VC supplementation. Thus, we demonstrated for the first time that 5-HMF increases HIF-1α stability by reducing the VC content, which mediates the protection against hypoxia.

Electrochromic properties of TiO2 nanotubes coated with electrodeposited MoO3.

Despite a favourable morphology, anodized and ordered TiO2 nanotubes are incapable of showing electrochromic properties in comparison to many other metal oxide counterparts. To tackle this issue, MoO3 of ~5 to 15 nm thickness was electrodeposited onto TiO2 nanotube arrays. A homogenous MoO3 coating was obtained and the crystal phase of the electrodeposited coating was determined to be α-MoO3. The electronic and optical augmentations of the MoO3 coated TiO2 platforms were evaluated through electrochromic measurements. The MoO3/TiO2 system showed a 4-fold increase in optical density over bare TiO2 when the thickness of the MoO3 coating was optimised. The enhancement was ascribed to (a) the α-MoO3 coating reducing the bandgap of the composite material, which shifted the band edge of the TiO2 platform, and subsequently increased the charge carrier transfer of the overall system and (b) the layered morphology of α-MoO3 that increased the intercalation probability and also provided direct pathways for charge carrier transfer.

Mechanism and dose-effect of Ginkgolide B on severe acute pancreatitis of rats.

AIM: To determine the optimal dosage and mechanism of Ginkgolide B (BN52021) on severe acute pancreatitis (SAP) of rats. METHODS: Seventy male Wistar rats were randomly divided into seven groups (10 for each group). Sham-operation group (SO), SAP model group (SAP), dimethyl sulfoxide (DMSO) contrast group (DMSO), and groups treated with 2.5 mg/kg BN52021 (BN1), 5 mg/kg BN52021 (BN2), 10 mg/kg BN52021 (BN3), and 20 µg/kg Sandostatin (SS). The SAP model was established in Wistar rats by injecting 5% sodium taurocholate retrogradely into the common bilio-pancreatic duct. The rats of SO, DMSO and BN52021 were injected with 0.9% NaCl, 0.5% DMSO and BN52021 through femoral vein 15 min after the operation. The SS group was injected with Sandostatin subcutaneously. All rats were anaesthetized at 6 h after operation, and venous blood was collected to determine the levels of serum amylase and phospholipase A2 (PLA2), and pancreas tissue was harvested and stained. RESULTS: There was no significant difference between the SAP and DMSO groups in serum amylase level, PLA2, ascites and pathologic score, but significant difference was found in SAP/DMSO groups compared with those in SO group (P < 0.05) and the levels of serum amylase, PLA2, ascites, and pathologic score were lower in the BN1, BN2, BN3 and SS groups than in the SAP and DMSO groups (P < 0.05). However, among BN1, BN2, BN3 and SS groups, BN2 had the best effect in decreasing the levels of serum amylase and PLA2 (P < 0.05). Expression of platelet activating factor (PAF) receptor (PAFR) mRNA and protein showed no significant difference between the SAP and DMSO groups, or among BN1, BN2, BN3 and SS groups, but there was remarkable difference between SAP/DMSO group and SO group (P < 0.05), and expression of PAFR mRNA and protein was higher in the BN1, BN2, BN3 and SS groups than in the SAP and DMSO groups (P < 0.05). PAFR expression was observed in the nucleus and cytoplasm of pancreatic islet cells in Wistar rats by immunohistochemistry. CONCLUSION: By iv injection, 5 mg/kg of BN52021 is the optimal dosage for SAP rats. BN52021 may inhibit the interaction/binding of PAF with PAFR.

G[alpha]i2 and G[alpha]q expression change in pancreatic tissues and BN52021 effects in rats with severe acute pancreatitis.

OBJECTIVE: To investigate change of G[alpha]i2, G[alpha]q mRNA, and their proteins in severe acute pancreatitis (SAP) and BN52021 effects. METHODS: Rats were assigned into negative-controlled group (NC), SAP-modeled group (SAP), and BN52051-remedial group (BN). Each group was assigned into 6 subgroups at different time points. G[alpha]i2, G[alpha]q mRNA, and their proteins were determined. RESULTS: In the SAP group, G[alpha]i2 at 12 and 24 hours and G[alpha]q at 1 and 6 hours were remarkably higher than those in the NC group; in the BN Group, G[alpha]i2 is not remarkably different from that in the SAP group, but G[alpha]q at 1 and 6 hours was lower than those in the SAP group (P < 0.01), and G[alpha]i2 at 12 hours was higher than that in the NC group (P < 0.05), but G[alpha]q was not remarkably different from that in the NC group; in the SAP group, G[alpha]i2 and G[alpha]q proteins were higher than those in the NC group (P < 0.05); in the BN group, G[alpha]i2 proteins at 6, 12, and 24 hours and G[alpha]q proteins were lower than those in the SAP group (P < 0.05), and G[alpha]i2 and G[alpha]q proteins at each time phase point except 24 hours were higher than those in the NC group (P < 0.05). CONCLUSIONS: G[alpha]i2, G[alpha]q mRNA, and their proteins in SAP increase. BN52021 decreases G[alpha]i2 and G[alpha]q.

A new dibenzofuran and other constituents from Ligularia caloxantha, a Chinese medicinal plant.

A new dibenzofuran named 1,2,4-trimethyl-7,8-dimethoxy-dibenzofuran (1), together with seven known compounds, euparin (2), 2,5-diacetyl-6-hydroxy-benzofuran (3), 2-acetyl-5,6-dimethoxy-benzofuran (4), gummosogenin (5), lupeol (6), stigmasterol (7) and (E)-2,5-dihydroxy-cinnamic acid (8), were isolated from the roots of Ligularia caloxantha, a Chinese medicinal plant. The structures of the compounds were elucidated by spectroscopic methods.

[Effect of ginkgolide B on plasma levels of interleukin-12 and PAF in severe acute pancreatitis in rats].

AIM: To observe the levels of interleukin-12 (IL-12) and platelet activating factor (PAF) in severe acute pancreatitis (SAP) in rats and the efficacy of Ginkgolide B (BN52021) in treating SAP. METHODS: Wistar rats were randomly divided into 3 groups: model group (SAP), treatment group (BN) and negative control group (NC). SAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in Wistar rats. NC rats only receive abdominal incision. In groups of SAP and NC rats received the femoral vein injection of isotonic Na chloride 15 minutes after induction of SAP; in BN group,rats received BN52021 instead. After operation rats were sacrificed at 1, 6 and 12 hour for plasma IL-12 and PAF determined with ELISA. RESULTS: An increase of IL-12 in group BN was observed VS group SAP or group NC at 1 h stage (p = 0.011, P < 0.01). At 6 h or 12 h stage,an increase of IL-12 in group SAP was observed VS group NC (P < 0.01, P < 0.05). The plasma level of PAF in group SAP or group BN was increased significantly at 1 h time stage VS group NC (P < 0.001). At 6 h or 12 h stage, a decrease of PAF in group BN or group NC was observed VS group SAP (P < 0.05, P < 0.01). CONCLUSION: It confirmed that the plasma level of cytokine IL-12 in SAP group was decreased significantly in early stage and it witnessed a remarkable increase of cytokine PAF. The plasma level of IL-12 was increased in early stage but PAF was decreased in rats treatment by BN52021 which inhibited the development of SAP.

Significance of platelet activating factor receptor expression in pancreatic tissues of rats with severe acute pancreatitis and effects of BN52021.

AIM: To investigate the dynamic changes and significance of platelet activating factor receptor (PAF-R) mRNA and protein in pancreatic tissues of rats with severe acute pancreatitis (SAP) and effects of BN52021 (Ginkgolide B). METHODS: Wistar male rats were randomly assigned to the negative control group (NC group), SAP model group (SAP group), and BN52051-remedy group (BN group), and each of the groups was divided into 6 subgroups at different time points after operation (1 h, 2 h, 3 h, 6 h, 12 h, and 24 h) (n = 10 in each). PT-PCR and Western blot methods were used to detect PAF-RmRNA and protein expression in pancreatic tissues of rats respectively. Pathological examination of pancreatic tissues was performed and the serum amylase change was detected. RESULTS: Serum amylase and pathological results showed the that SAP model was successfully prepared, BN52021 was able to decrease serum amylase, and the pathological ratings in BN group at 3 h, 6 h, and 12 h significantly decreased compared with those in the SAP group (8.85 +/- 0.39 vs 5.95 +/- 0.19, 9.15 +/- 0.55 vs 5.55 +/- 0.36, 10.10 +/- 0.65 vs 6.72 +/- 0.30, P < 0.05). The result of PAF-mRNA showed dynamic changes in SAP and BN groups, which increased gradually in early stage, reached a peak at 3 h (0.71 +/- 0.14 vs 0.54 +/- 0.14, 0.69 +/- 0.13 vs 0.59 +/- 0.04, P < 0.05), and decreased gradually later. There were significant differences at each time point except 1 h and 2 h, when compared with those in the NC group (0.71 +/- 0.14 or 0.69 +/- 0.13 vs 0.47 +/- 0.10, 0.38 +/- 0.08 or 0.59 +/- 0.04 vs 0.47 +/- 0.09, 0.25 +/- 0.07 or 0.29 +/- 0.05 vs 0.46 +/- 0.10, 0.20 +/- 0.06 or 0.20 +/- 0.04 vs 0.43 +/- 0.09, P < 0.05), whereas there was no significant difference between BN and SAP groups at each time point. The result of PAF-R protein showed that the change of PAF-R protein in the SAP group and the BN group was consistent with that of PAF-R mRNA. There were significant differences at each time point except 1 h, when compared with those in the NC group (0.90 +/- 0.02 or 0.80 +/- 0.05 vs 0.48 +/- 0.02, 1.69 +/- 0.06 or 1.58 +/- 0.02 vs 0.48 +/- 0.03, 1.12 +/-0.10 or 0.98 +/- 0.03 vs 0.49 +/- 0.09, 1.04 +/- 0.14 or 0.87 +/- 0.02 vs 0.52 +/- 0.08, 0.97 +/- 0.16 or 0.90 +/- 0.05 vs 0.49 +/- 0.10, P < 0.05), whereas there was no significant difference between the BN group and the SAP group. CONCLUSION: PAF-R plays an important role in occurrence and development of SAP. BN52021 exerts biological effects through competitively inhibiting the binding of increased both PAF and PAF-R expression rather than through decreasing PAF-R expression in pancreatic tissues.

Effect of BN52021 on NFkappa-Bp65 expression in pancreatic tissues of rats with severe acute pancreatitis.

AIM: To investigate dynamic changes and significance of expression of NF-kappaBp65 in pancreatic tissues of rats with severe acute pancreatitis (SAP), as well as BN52021 effects. METHODS: Wistar male rats were randomly divided into negative control group (NC group, n=60), SAP-model group (SAP group, n=60), and BN52021-treated group (BN group, n=60), and each of the above groups was respectively divided into 6 subgroups at different time points after operation (1 h, 2 h, 3 h, 6 h, 12 h, and 24 h) (n=10). By RT-PCR and Western blot, NF-kappaBp65 mRNA and its protein expression in pancreatic tissues of rats were detected respectively. RESULTS: The expression of NF-kappaBp65 mRNA dynamically changed in both SAP groups and BN groups. The mRNA level was higher in SAP groups than NC groups at 2 h, 3 h, 12 h, and 24 h after operation (P<0.05), higher in BN groups than NC groups at all time points (P<0.05), and higher in BN groups than SAP group at 1 h (P<0.05). The NF-kappaBp65 protein level was higher in SAP groups than NC groups at 1 h, 3 h, and 6 h (P<0.01), and 2 h, 12 h, and 24 h (P<0.05), higher in BN groups than NC groups at all time points (P<0.05), and lower in BN groups than SAP groups at 1 h, 3 h, and 6 h (P<0.05). CONCLUSION: The expression of NF-kappaBp65 in pancreatic tissues is dynamically changed and the changes play an important role in pathogenesis of SAP. BN52021 exerts therapeutic effects through reducing the expression level of NF-kappaBp65 protein in the early stage of SAP.

Effect of yiqi huoxue recipe on cardiac function and ultrastructure in regression of pressure overload-induced myocardial hypertrophy in rats.

OBJECTIVE: To investigate the effect of Yiqi Huoxue Recipe (YHR) on the cardiac function and ultrastructure during the regression of myocardial hypertrophy induced by pressure overload in rats. METHODS: The model of myocardial hypertrophy was established by abdominal aortic banding. Eighty male Wistar rats were divided into six groups, the normal control group I (n=20), the normal control group II (n=12), the hypertension model group I (n=12), the hypertension model group II (n=12), the YHR group (n=12) and the Captopril group (n=12). The observation was carried out in the normal control group I and the hypertension model group I after 4 weeks of modeling, and the other four groups were observed after 16 weeks of modeling (12 weeks of administration). The cardiac function was measured with a multichannel biological signal analysis system, and the myocardium ultrastructure was observed by a transmission electron microscope. RESULTS: (1) Compared with the normal control group I, the systolic blood pressure and cardiac coefficient (left ventricular weight/body weight) in the model I group was higher (P<0.05, P<0.01). (2) In the YHR group, cardiac coefficient and -dp/dt(max) were lower, left ventricular systolic pressure and +dp/dt(min) were higher when compared with the model group II and the Captopril group (P<0.05 or P<0.01). In the Captopril group, only cardiac coefficient was lower when compared with the mode group II (P<0.05). (3) Compared with the normal control group II, +dp/dt(max) was higher (P<0.01) -dp/dt(max) and isovolumetric contraction time (ICT) was lower (P<0.05, P<0.01) in both the YHR group and the Captopril group. (4) Results of the myocardium ultrastructure showed edema under myocardium plasmalemma, enlarged sarcoplasmic reticulum and T tube, and significantly enlarged intercalated disc of the cardiac muscle in the model groups. In the Captopril group, the extension of sarcoplasmic reticulum and T tube as well as the pathological changes of intercalated disc were lighter, with slight edema under the myocardium plasmalemma. In the YHR group, the expansion of the sarcoplasmic reticulum was less than in the Captopril group, part of the pathological changes of intercalated discs was slightly more severe than that in the Captopril group, the dissolution of nuclear chromatin was not found, which was similar to that of the Captopril group, and no injury of the nucleus was found, either. CONCLUSION: YHR could reverse myocardial hypertrophy in rats with abdominal aortic banding and improve the systolic and diastolic function of the left ventricle. The ultrastructure of the myocardium such as arcoplasmic reticulum, intercalated disc, and cell nucleus in abdominal aortic banding rats could be partly reversed by the recipe.