Impairment of the blood-brain barrier (BBB) in severe acute pancreatitis (SAP) could result in life-threatening pancreatic encephalopathy. Interleukin-10 (IL-10) is a classical cytokine that is well-known for its strong immunoregulatory and anti-inflammatory abilities. However, whether and how IL-10 protects the BBB in SAP are still unclear. This study includes in vivo experiments using a SAP rat model and in vitro experiments using an in vitro BBB model consisting of a monolayer of brain microvascular endothelial cells (BMECs). The study groups are divided into the control, SAP (in vivo)/TNF-α (in vitro), IL-10 treatment, IL-10 + signal transducer and activator of transcription 3 (STAT3) inhibitor S3I-201 treatment groups. Pancreatic pathological scores, serum amylase, serum TNF-α levels and BBB permeability by Evan’s blue assay in SAP rat models were evaluated. BMEC apoptosis in SAP rats or induced by TNF-αin vitro was detected by terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) and flow cytometry, separately. Expression levels of claudin-5 and proteins involved in the STAT3 signaling pathway were measured by Western blotting. Location and changes of junctional structure of claudin-5 on BMECs were assessed by immunohistochemistry and immunofluorescence. In vivo, IL-10 alleviated the severity of inflammation, attenuated the increased BBB permeability in SAP rat models by reducing BMEC apoptosis via the STAT3 pathway and ameliorated the down-regulation of claudin-5 expression in BMECs; in vitro, IL-10 improved BBB integrity against TNF-α by attenuating BMEC apoptosis via the STAT3 pathway, the impairment of tight junction structure and the down-regulation of claudin-5 expression in BMECs. IL-10 improves BBB properties in SAP by attenuating the down-regulation of claudin-5 expression and the impairment of tight junctions and by STAT3 pathway-mediated anti-apoptotic effects on BMECs.

Idiopathic thrombocytopenic purpura (ITP) is a common hematological disease and the abnormal platelet destruction in the spleen is a critical pathological mechanism for ITP. However, the metabolomic change in the spleen caused by ITP is still unclear. In the present study, the metabolomic information of 18 ITP and 20 normal spleen samples were detected by using ¹H high-resolution magic angle spinning NMR spectroscopy (¹H MAS NMR). Compared with normal spleen, the concentrations of acetate, alanine, glutamine, glycerol, isoleucine, lysine, valine, phenylalanine, leucine, and methanol in ITP spleen tissue were elevated and 3-hydroxybutyric acid, ascorbate, asparagine, ethanol, glycogen, low-density lipoprotein, malonate, myo-inositol, glycerophosphocholine, pyroglutamate, and taurine were decreased. Amino acids metabolic pathways, such as branched-chain amino acids pathway, were identified as the main involved pathways based on enrichment analysis. The decrease in taurine level in the spleen was the most obvious metabolic signature involving ITP with high sensitivity and specificity to distinguish the spleen of ITP from the normal (CI: 0.825–0.982). Notably, the level of taurine in the spleen was negatively correlated with the efficacy of splenectomy (r = 0.622, p = 0.006). Collectively, the data from our study revealed previously unknown ITP-related metabolomic changes in the spleen and found a potential diagnostic and efficacy-predictive biomarker for ITP treatment.

The differentiation of pancreatic ductal adenocarcinoma (PDAC) could be associated with prognosis and may influence the choices of clinical management. No applicable methods could reliably predict the tumor differentiation preoperatively. Thus, the aim of this study was to compare the metabonomic profiling of pancreatic ductal adenocarcinoma with different differentiations and assess the feasibility of predicting tumor differentiations through metabonomic strategy based on nuclear magnetic resonance spectroscopy. By implanting pancreatic cancer cell strains Panc-1, Bxpc-3 and SW1990 in nude mice in situ, we successfully established the orthotopic xenograft models of PDAC with different differentiations. The metabonomic profiling of serum from different PDAC was achieved and analyzed by using 1H nuclear magnetic resonance (NMR) spectroscopy combined with the multivariate statistical analysis. Then, the differential metabolites acquired were used for enrichment analysis of metabolic pathways to get a deep insight. An obvious metabonomic difference was demonstrated between all groups and the pattern recognition models were established successfully. The higher concentrations of amino acids, glycolytic and glutaminolytic participators in SW1990 and choline-contain metabolites in Panc-1 relative to other PDAC cells were demonstrated, which may be served as potential indicators for tumor differentiation. The metabolic pathways and differential metabolites identified in current study may be associated with specific pathways such as serine-glycine-one-carbon and glutaminolytic pathways, which can regulate tumorous proliferation and epigenetic regulation. The NMR-based metabonomic strategy may be served as a non-invasive detection method for predicting tumor differentiation preoperatively.