Network pharmacology analysis and molecular mechanism of paeoniflorin and its metabolite in prolactinoma cells.

Prolactinoma was the most common functional pituitary neuroendocrine tumor tissue type, which was caused by excessive proliferation of pituitary prolactin (PRL) cells. Drug therapy of dopamine receptor agonists was generally considered as the prior treatment for prolactinoma patients. However, there were still prolactinoma patients who were resistant to dopamine agonists. Studies have been reported that paeoniflorin can inhibit the secretion of PRL in prolactinoma cells lacking dopamine D2 receptor (D2R) expression, and paeoniflorin can be metabolized into albiflorin by intestinal flora in rats. The effect of albiflorin on prolactinoma has not been reported yet. In this study, network pharmacology was used to analyze the mechanism of paeoniflorin and its metabolite albiflorin as multi-target therapy for prolactinoma, and the experimental verification was carried out. In order to clarify the complex relationship among paeoniflorin, albiflorin and prolactinoma, we constructed a component-target-disease network, and further constructed interaction network, MMP9, EGFR, FGF2, FGFR1 and LGALS3 were screened as the core targets. Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that paeoniflorin and albiflorin may be involved in various pathways in the treatment of prolactinoma, included relaxin signaling pathway and PI3K-Akt signaling pathway. Molecular docking analysis showed that paeoniflorin and albiflorin had good binding activity with MMP9. Western blotting results showed that paeoniflorin and albiflorin could significantly reduce the expression of MMP9, and ELISA results showed that paeoniflorin and albiflorin could significantly reduce the concentration of PRL in GH3 cells, and the reduce degree of albiflorin was stronger than paeoniflorin at 50 µM, which indicated that albiflorin might be a potential drug to treat prolactinoma, which can regulate prolactinoma through MMP9 and reduce the concentration of PRL. Our study provided a new therapeutic strategy for prolactinoma.

Prognostic and immunological roles of heat shock protein A4 in lung adenocarcinoma.

BACKGROUND: Heat shock protein A4 (HSPA4) belongs to molecular chaperone protein family which plays important roles within variable cellular activities, including cancer initiation and progression. However, the prognostic and immunological significance of HSPA4 in lung adenocarcinoma (LUAD) has not been revealed yet. AIM: To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD. METHODS: We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database. The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test. Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors, including HSPA4, in LUAD. Gene set enrichment analysis (GSEA) was conducted to identify the key signaling pathways associated with HSPA4. The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis (ssGSEA). RESULTS: Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage, advanced pathologic stage, progression disease status of primary therapy outcome and female subgroups with LUAD. In addition, increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival. GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response, particularly through diminishing the function of cytotoxicity cells and CD8 T cells. The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells, while a negative correlation was observed with cytotoxic cell infiltration levels. CONCLUSION: Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.

Simultaneous Detection of Two Extracellular Vesicle Subpopulations in Saliva Assisting Tumor T Staging of Oral Squamous Cell Carcinoma.

Extracellular vesicles (EVs), acting as important mediators of intercellular communication, play an essential role in physiological processes, which have unique potential in the medical field. However, the heterogeneity of EVs limits their development for disease diagnosis and therapy, making the EV subpopulation analysis extremely valuable. In this article, a simple microfluidic approach was presented for the on-chip specific isolation and detection of two phenotypes of EVs (Annexin V+ EGFR+ EVs and Annexin V- EGFR+ EVs) based on different biomolecule-modified magnetic nanospheres and a fluorescence labeling technique. Combined with the control of the magnetic field in the microzone and fluid flow, it was easy to form two separate functional regions in the chip to capture different EV subpopulations. This method was successfully applied to the tests of clinical saliva samples in 75 oral squamous cell carcinoma (OSCC) patients and 10 healthy people. The results showed that the total level of EGFR+ EVs was much higher in OSCC patients that in healthy people. Meantime, the ratio of Annexin V+ EGFR+ EVs to Annexin V- EGFR+ EVs was found to be negatively correlated with tumor T stage of OSCC patients with a statistical difference, which suggested the ratio as a clinical index for monitoring the progression of OSCC in real time based on a noninvasive method. The approach provided a novel idea for evaluating the tumor T stage of OSCC and a powerful tool for clinical application.

Neutral 1D Perovskite-Type ABX3 Phase Transition Material with a Narrowband Emission and Semiconductor Property.

Cyclic organic amines are emerging as excellent building blocks to assemble organic-inorganic hybrid phase transition materials due to their flexible cyclic structure. Here, we have assembled a 1D organic-inorganic hybrid dielectric material C5 H6 NOPbBr3 (1) by alloying the cyclic organic amine 3-hydroxypyridine. 1 displays a remarkable switchable dielectric response induced by an order-disorder transformation of the organic moiety, this transformation behaviour is confirmed by DSC and Hirshfeld surface measurements. More interestingly, 1 has a narrowband emission (FWHM=4.64 nm) at 590 nm; FWHM is a major quality figure for narrowband photodetectors. In addition, 1 exhibits semiconducting properties with an indirect bandgap of 2.78 eV by the analysis of the UV-Vis absorption results.

Distinct Proteomic Profiling of Plasma Extracellular Vesicles from Moderate-to-Severe Atopic Dermatitis Patients.

BACKGROUND: Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disorder characterized by a T helper 2 (Th2) immune response phenotype. Extracellular vesicles (EVs) are a heterogeneous family of cell-derived membranous structures, which transport cellular components such as DNA and proteins, and are involved in multiple physiological and pathological processes. Increasing evidence has shown that EVs secretion took part in the pathogenesis of AD. However, the proteomic studies of plasma-derived EVs in AD patients have not been reported. OBJECTIVE: In this study, we investigated the diversity of plasma EVs collected from AD patients and healthy individuals and suggested that the candidates for uniquely or differentially expressed proteins in plasma EVs could be a diagnostic marker in AD. METHODS: The plasma EVs were collected from 12 patients with moderate-to-severe AD and 13 healthy subjects. Proteomic analysis was performed by using a comprehensive nanoLC­MS/MS method. RESULTS: Proteomic analysis revealed that a total of 1478 proteins in plasma EVs were found to be common proteins in AD, whereas a total of 1597 proteins in plasma EVs were found to be common proteins in HC. Eighty-six proteins in plasma EVs showed more than 2.5-fold up-regulation, while a total of 225 proteins in plasma EVs showed less than 1/2.5-fold down-regulation with a significant difference (p < 0.05) among AD compared with HC. The candidates for differentially expressed proteins in plasma EVs have been described as a connectivity PPI network related to several KEGG pathways, including pathways in platelet activation, complement, and so on. CONCLUSION: SLP-76 tyrosine phosphoprotein (SLP76) involved in platelet activation may significantly contribute to the pathogenesis of AD. We will further verify the role of SLP67 in AD via animal and cell experiments to provide a promising therapeutic or diagnostic target.

Identification of a new azoreductase driven prodrug from bardoxolone methyl and 5-aminosalicylate for the treatment of colitis in mice.

For local treatment of ulcerative colitis, a new azoreductase driven prodrug CDDO-AZO from bardoxolone methyl (CDDO-Me) and 5-aminosalicylate (5-ASA) was designed, synthesized and biologically evaluated. It is proposed that orally administrated CDDO-AZO is stable before reaching the colon, while it can also be triggered by the presence of azoreductase in the colon to fragment into CDDO-Me and 5-ASA, generating potent anti-colitis effects. Superior to olsalazine (OLS, a clinically used drug for ulcerative colitis) and CDDO-Me plus 5-ASA, CDDO-AZO significantly attenuated inflammatory colitis symptoms in DSS-induced chronic colitis mice, which suggested that CDDO-AZO may be a promising anti-ulcerative colitis agent.

Variation in textural parameters of hepatic lesions during contrast medium injection.

BACKGROUND: Textural parameters extracted using quantitative imaging techniques have been shown to have prognostic value for hepatocellular carcinoma (HCC). PURPOSE: To evaluate whether the contrast medium timing of the image acquisition affects the reproducibility of textural parameters in HCC and hepatic tissue. MATERIAL AND METHODS: This retrospective study included 17 patients with 37 HCC lesions. Perfusion computed tomography (CT) was obtained after 50 mL contrast medium injection. HCC lesions were segmented for analysis. The gray-level co-occurrence (GLCM) textural analysis parameters, homogeneity, energy, entropy, inertia, and correlation were calculated. Variation was quantified by calculating the SD of each parameter during respective perfusion series and the inter lesion variation as the SD among the lesions. RESULTS: The average change in texture parameters in both HCC and hepatic tissue per second after injection was 0.01% to 0.3% of the respective texture parameter. In HCC, the average variation in homogeneity, energy, and entropy within each lesion after contrast medium injection was significantly less than the variation observed among the lesions (23% to 74%, P < 0.001). Significant differences in energy, entropy, inertia, and correlation between hepatic tissue and HCC were observed. However, when considering the intra-individual variation of hepatic tissue over time, only the HCC parameter energy was significantly outside that 95% confidence interval (P < 0.02). CONCLUSION: The contrast medium timing does not affect the reproducibility of textural parameters in HCC and hepatic tissue. Thus, contrast medium timing should not be an issue at CT texture analysis of HCC.

Design, synthesis, and biological evaluation of ligustrazine/resveratrol hybrids as potential anti-ischemic stroke agents.

To search for potent anti-ischemic stroke agents, a series of tetramethylpyrazine (TMP)/resveratrol (RES) hybrids 6a-t were designed and synthesized. These hybrids inhibited adenosine diphosphate (ADP)- or arachidonic acid (AA)-induced platelet aggregation, among them, 6d, 6g-i, 6o and 6q were more active than TMP. The most active compound 6h exhibited more potent anti-platelet aggregation activity than TMP, RES, as well as positive control ticlopidine (Ticlid) and aspirin (ASP). Furthermore, 6h exerted strong antioxidative activity in a dose-dependent manner in rat pheochromocytoma PC12 cells which were treated with hydrogen peroxide (H2O2) or hydroxyl radical (·OH). Importantly, 6h significantly protected primary neuronal cells suffered from oxygen-glucose deprivation/reoxygenation (OGD/R) injury, comparable to an anti-ischemic drug edaravone (Eda). Together, our findings suggest that 6h may be a promising candidate warranting further investigation for the intervention of ischemic stroke.

Nitric oxide donating anti-glaucoma drugs: advances and prospects.

Glaucoma is a disease that causes irreversible blindness. Reducing intraocular pressure (IOP) is the main treatment at present. Nitric oxide (NO), an endogenous gas signaling molecule, can increase aqueous humor outflow facility, inhibit aqueous humor production thereby reducing IOP, as well as regulate eye blood flow and protect the optic nerve. Therefore, NO donating anti-glaucoma drugs have broad research prospects. In this review, we summarize NO-mediated therapy for glaucoma, and the state of the art of some NO donating molecules, including latanoprostene bunod in market and some other candidate compounds, for the intervention of glaucoma, as well as prospects and challenges ahead in this field.

Solvent Effects on Morphology and Electrical Properties of Poly(3-hexylthiophene) Electrospun Nanofibers.

Herein, poly(3-hexylthiophene-2,5-diyl) (P3HT) nanofiber-based organic field-effect transistors were successfully prepared by coaxial electrospinning technique with P3HT as the core polymer and poly(methyl methacrylate) (PMMA) as the shell polymer, followed by extraction of PMMA. Three different solvents for the core polymer, including chloroform, chlorobenzene and 1,2,4-trichlorobenzene, were employed to manipulate the morphologies and electrical properties of P3HT electrospun nanofibers. Through the analyses from dynamic light scattering of P3HT solutions, polarized photoluminescence and X-ray diffraction pattern of P3HT electrospun nanofibers, it is revealed that the P3HT electrospun nanofiber prepared from the chloroform system displays a low crystallinity but highly oriented crystalline grains due to the dominant population of isolated-chain species in solution that greatly facilitates P3HT chain stretching during electrospinning. The resulting high charge-carrier mobility of 3.57 × 10-1 cm2·V-1·s-1 and decent mechanical deformation up to a strain of 80% make the P3HT electrospun nanofiber a promising means for fabricating stretchable optoelectronic devices.

Computed tomography volumetry of esophageal cancer - the role of semiautomatic assessment.

BACKGROUND: The clinical and research value of Computed Tomography (CT) volumetry of esophageal cancer tumor size remains controversial. Development in CT technique and image analysis has made CT volumetry less cumbersome and it has gained renewed attention. The aim of this study was to assess esophageal tumor volume by semi-automatic measurements as compared to manual. METHODS: A total of 23 esophageal cancer patients (median age 65, range 51-71), undergoing CT in the portal-venous phase for tumor staging, were retrospectively included between 2007 and 2012. One radiology resident and one consultant radiologist measured the tumor volume by semiautomatic segmentation and manual segmentation. Reproducibility of the respective measurements was assessed by intraclass correlation coefficients (ICC) and by average deviation from mean. RESULTS: Mean tumor volume was 46 ml (range 5-137 ml) using manual segmentation and 42 ml (range 3-111 ml) using semiautomatic segmentation. Semiautomatic measurement provided better inter-observer agreement than traditional manual segmentation. The ICC was significantly higher for semiautomatic segmentation in comparison to manual segmentation (0.86, 0.56, p < 0.01). The average absolute percentage difference from mean was reduced from 24 to 14% (p < 0.001) when using semiautomatic segmentation. CONCLUSIONS: Semiautomatic analysis outperforms manual analysis for assessment of esophageal tumor volume, improving reproducibility.

Body composition evaluation with computed tomography: Contrast media and slice thickness cause methodological errors.

OBJECTIVE: Although computed tomography (CT) is frequently used to determine body composition, the effects of using different CT protocols is not well known. The aim of this study was to determine whether contrast media phase, radiation dose, and slice thickness in CT affect body composition segmentation. METHODS: Clinically indicated perfusion CTs of the upper abdomen in 20 patients (seven women) between 40 and 87 y of age with high suspicion of hepatocellular carcinoma were analyzed retrospectively. Axial images from the L3 level with varying imaging delay were reconstructed after contrast media injection (18 images per patient), slice thickness (5 images, 2-10 mm), and radiation dose (4 images with one-third to four-thirds of standard dose). Muscle and fat areas were segmented semiautomatically by drawing regions of interests and using established cutoff thresholds. Skeletal muscle index (SMI), steatotic muscle area, and adipose tissue index, as well as muscle attenuation and fat attenuation, were evaluated. RESULTS: Average SMI increased by up to 2.8% after contrast media injection. Steatotic muscle area decreased by ≤13.8%, and adipose tissue index decreased by ≤6.5%. Muscle attenuation increased after contrast media injection, whereas fat attenuation decreased (all P < 0.001). SMI decreased by 1.9% on average when increasing slice thickness from 2 to 10 mm. Steatotic muscle area increased by ≤3.3%, and adipose tissue index increased by ≤1.5% (all P < 0.05). Muscle attenuation did not change significantly with reconstruction thickness. Radiation dose had no effect on estimated area of spinal muscle, fatty spinal muscle, or visceral fat. CONCLUSIONS: Contrast media have a strong effect on the evaluation of body composition, whereas the influence of slice thickness is less pronounced. Radiation dose can be reduced by ≥66% without significantly affecting segmentation.

Influence of tube potential on CT body composition analysis.

OBJECTIVES: Our purpose was to investigate whether tube potential in contrast-enhanced computed tomography (CT) affects body composition analysis. METHODS: Images from dual-source, dual-energy CT from the abdomen with intravenous contrast media administration were used. A total of 17 patients (11 women, mean age 52) with a mean body mass index of 20.8 kg/cm2 were included. Simultaneously acquired images with a tube voltage of 80 kV and 140 kV were compared. Body composition was analyzed on a single slice at the L3 level. Parameters evaluated included muscle and fat attenuation (Hounsfield units [HU]), skeletal muscle index (cm2/m2), muscle area (cm2), and steatotic muscle area (cm2). Significant differences between 80 kV and 140 kV series were compared using the paired Student's t test. RESULTS: Tube potential affected muscle attenuation with an average difference of 17% between 80 kV and 140 kV series (48 HU versus 41 HU, P < 0.01), fat attenuation (-84 HU versus -69 HU, P < 0.01), skeletal muscle index of 5.2% (40.1 cm2/m2 versus 42.2 cm2/m2, P < 0.01), muscle area of 5.1% (117 cm2 versus 123 cm2, P < 0.01), and steatotic muscle area of 12.9% (31 cm2 versus 35 cm2, P < 0.01). CONCLUSION: Tube potential significantly affects body segmentation in contrast-enhanced CT.

Quantitative texture analysis in the prediction of IDH status in low-grade gliomas.

OBJECTIVES: Molecular markers provide valuable information about treatment response and prognosis in patients with low-grade gliomas (LGG). In order to make this important information available prior to surgery the aim of this study was to explore if molecular status in LGG can be discriminated by preoperative magnetic resonance imaging (MRI). PATIENTS AND METHODS: All patients with histopathologically confirmed LGG with available molecular status who had undergone a preoperative standard clinical MRI protocol using a 3T Siemens Skyra scanner during 2008-2015 were retrospectively identified. Based on Haralick texture parameters and the segmented LGG FLAIR volume we explored if it was possible to predict molecular status. RESULTS: In total 25 patients (nine women, average age 44) fulfilled the inclusion parameters. The textural parameter homogeneity could discriminate between LGG patients with IDH mutation (0.12, IQR 0.10-0.15) and IDH wild type (0.07, IQR 0.06-0.09, p=0.005). None of the other four analyzed texture parameters (energy, entropy, correlation and inertia) were associated with molecular status. Using ROC curves, the area under curve for predicting IDH mutation was 0.905 for homogeneity, 0.840 for tumor volume and 0.940 for the combined parameters of tumor volume and homogeneity. We could not predict molecular status using the four other chosen texture parameters (energy, entropy, correlation and inertia). Further, we could not separate LGG with IDH mutation with or without 1p19q codeletion. CONCLUSIONS: In this preliminary study using Haralick texture parameters based on preoperative clinical FLAIR sequence, the homogeneity parameter could separate IDH mutated LGG from IDH wild type LGG. Combined with tumor volume, these diagnostic properties seem promising.

Synthesis and evaluation of 2-cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13ß, 28-olide as a potent anti-inflammatory agent for intervention of LPS-induced acute lung injury.

The present study was designed to synthesize 2-Cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13ß, 28-olide (1), a lactone derivative of oleanolic acid (OA) and evaluate its anti-inflammatory activity. Compound 1 significantly diminished nitric oxide (NO) production and down-regulated the mRNA expression of iNOS, COX-2, IL-6, IL-1ß, and TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Further in vivo studies in murine model of LPS-induced acute lung injury (ALI) showed that 1 possessed more potent protective effects than the well-known anti-inflammatory drug dexamethasone by inhibiting myeloperoxidase (MPO) activity, reducing total cells and neutrophils, and suppressing inflammatory cytokines expression, and thus ameliorating the histopathological conditions of the injured lung tissue. In conclusion, compound 1 could be developed as a promising anti-inflammatory agent for intervention of LPS-induced ALI.

Synthesis and anti-hepatocellular carcinoma activity of novel O2-vinyl diazeniumdiolate-based nitric oxide-releasing derivatives of oleanolic acid.

Considering that high levels of nitric oxide (NO) exert anti-cancer effect and the derivatives of oleanolic acid (OA) have shown potent anti-cancer activity, new O2-vinyl diazeniumdiolate-based NO releasing derivatives (5a-l, 11a-l) of OA were designed, synthesized, and biologically evaluated in the present study. These derivatives could release different amounts of NO in liver cells. Among them, 5d, 5i, 5j, 11g, 11h, and 11j released more NO in SMMC-7721 cells and displayed stronger proliferative inhibition against SMMC-7721 and HepG2 cells than OA and other tested compounds. The most active compound 5j showed almost 20-fold better solubility than OA in aqueous solution, released larger amounts of NO in liver cancer cells than that in normal ones, and exhibited potent anti-hepatocellular carcinoma activity but little effect on the normal liver cells. The inhibitory activity against the cancer cells was significantly diminished upon addition of an NO scavenger, suggesting that NO may contribute, at least in part, to the activity of 5j.

5d, a novel analogue of 3-n-butylphthalide, decreases NADPH oxidase activity through the positive regulation of CK2 after ischemia/reperfusion injury.

5d, a novel analogue of the racemic 3-n-butylphthalide (NBP), has been reported for its free radical scavenging activity in vitro and preventive neuroprotection in vivo. Nevertheless, the mechanism by which 5d attenuated ischemia/reperfusion (I/R) injury is still unknown. Our results showed that 5d significantly increased CK2 activity as well as CK2α and 2α' protein levels after I/R injury. Besides, 5d suppressed the translocation of cytosolic p47phox and Rac1 to the membrane, decreased NOX4 expression and ROS generation. Furthermore, 5d blocked the dissociation between CK2α and Rac1 so as to decrease NADPH oxidase activity. Based on these findings, we propose that the neuroprotective effect of 5d is due to an increase of CK2 activity, which blocks I/R-induced dissociation between CK2α and Rac1, decreases NADPH oxidase activity, inhibits ROS production and finally realizes the neuroprotection of I/R. These findings point to that 5d might be considered an attractive candidate for further studies in ischemic stroke.

[Advances in hydrogen sulfide and hydrogen sulfide-releasing drugs].

Hydrogen sulfide (H(2)S) is considered as a new member of gasotransmitter family, following nitric oxide (NO) and carbon monoxide (CO). H2S exerts important biological effects in mammals, which has drawn more and more attention in recent years. It is proved that H(2)S has a role in the regulation of physiological and pathophysiological processes in the cardiovascular system and the nervous system. Several cardiovascular and nervous diseases are connected to H(2)S. H(2)S-releasing agents (also known as H(2)S donors) have been widely used not only as useful research tools but also potential therapeutic agents. In this review, we provide an overview of the chemistry and biology of H(2)S, and summarize the chemistry and biological activity of some natural and synthetic H(2)S donors. We introduce the developments of currently available H(2)S-releasing drugs including H(2)S-non-steroidal anti-inflammatory drugs, H(2)S-nervous system drugs and NO-H(2)S-releasing drugs. We hope this review will be a value reference in the development of H(2)S-releasing drugs in the treatment of cardiovascular and nervous diseases.

Synthesis and biological evaluation of nitric oxide (NO)-hydrogen sulfide (H2S) releasing derivatives of (S)-3-n-butylphthalide as potential antiplatelet agents.

In the present study, a series of novel nitric oxide-hydrogen sulfide releasing derivatives of (S)-3-n-butylphthalide ((S)-NBP) were designed, synthesized, and evaluated as potential antiplatelet agents. Compound NOSH-NBP-5 displayed the strongest activity in inhibiting the arachidonic acid (AA)- and adenosine diphosphate (ADP)-induced platelet aggregation in vitro, with 3.8- and 7.0-fold more effectiveness than (S)-NBP, respectively. Furthermore, NOSH-NBP-5 could release moderate levels of NO and H2S, which would be beneficial in improving cardiovascular and cerebral circulation. Moreover, NOSH-NBP-5 could release (S)-NBP when incubated with rat brain homogenate. In conclusion, these findings may provide new insights into the development of novel antiplatelet agents for the treatment of thrombosis-related ischemic stroke.

Expression of phosphatidylinositol-3 kinase and effects of inhibitor Wortmannin on expression of tumor necrosis factor-α in severe acute pancreatitis associated with acute lung injury.

BACKGROUND: Acute lung injury (ALI) is a common and serious complication of severe acute pancreatitis (SAP). The study aimed to investigate the protective effect and mechanism of phosphatidylinositol-3 kinase (PI3K) inhibitor Wortmannin in SAP associated with ALI. METHODS: Ninety rats were randomly divided into three groups: sham operation (SO) group (n=30), SAP group (n=30), and SAP+Wortmannin (SAP+W) group (n=30). SAP model was induced by retrograde injection of 4% sodium taurocholate into the biliopancreatic duct of rats. The rate of lung water content, myeloperoxidase (MPO), matrix metalloproteinase 9 (MMP-9), protein kinase B (PKB), abdphosphorylation of protein kinase B (P-PKB) activity in the lung tissue were evaluated. RESULTS: In the SAP group, the p-PKB expression in the lung tissue began to rise at 3 hours after modeling, and peaked at 12 hours (P<0.05); the rate of lung water content, MPO and TNF-α activity were also gradually increased, and the degree of lung lesion gradually increased (P<0.05). In the SAP+Wortmannin group, the p-PKB expression in the lung tissue began to rise at 3 hours after modeling, and peaked at 12 hours; it was higher than that in the SO group (P<0.05), but significantly lower than that in the SAP group (P<0.05). The rest indicators in the SAP+Wortmannin group were also significantly decreased as compared with the SAP group (P<0.05). CONCLUSIONS: The expression of phosphatidylinositol-3 kinase/protein kinase B was elevated in severe pancreatitis rats with lung injury. This suggested that PI3K signal transduction pathway is involved in the control and release of proinflammatory cytokines TNF-α, which may play an important role in the pathogenesis of severe acute pancreatitis associated with lung injury. This finding indicated that Wortmannin can block the PI3K signal transduction pathway, and inhibit the release of inflammatory factor TNF-α.