Severe hepatic inflammation is a common cause of acute or chronic liver disease. Macrophages are one of the key mediators which regulate the progress of hepatic inflammation. Increasing evidence shows that the TAM (TYRO3, AXL and MERTK) family of RTKs (receptor tyrosine kinases), which is expressed in macrophages, alleviates inflammatory responses through a negative feedback loop. However, the functional contribution of each TAM family member to the progression of hepatic inflammation remains elusive. In this study, we explore the role of individual TAM family proteins during autophagy induction and evaluate their contribution to hepatic inflammation. Among the TAM family of RTKs, AXL (AXL receptor tyrosine kinase) only induces autophagy in macrophages after interaction with its ligand, GAS6 (growth arrest specific 6). Based on our results, autophosphorylation of 2 tyrosine residues (Tyr815 and Tyr860) in the cytoplasmic domain of AXL in mice is required for autophagy induction and AXL-mediated autophagy induction is dependent on MAPK (mitogen-activated protein kinase)14 activity. Furthermore, induction of AXL-mediated autophagy prevents CASP1 (caspase 1)-dependent IL1B (interleukin 1, β) and IL18 (interleukin 18) maturation by inhibiting NLRP3 (NLR family, pyrin domain containing 3) inflammasome activation. In agreement with these observations, axl mice show more severe symptoms than do wild-type (Axl) mice following acute hepatic injury induced by administration of lipopolysaccharide (LPS) or carbon tetrachloride (CCl). Hence, GAS6-AXL signaling-mediated autophagy induction in murine macrophages ameliorates hepatic inflammatory responses by inhibiting NLRP3 inflammasome activation.

BackgroundThe ankle brachial pressure index (ABI) is a simple, useful method for diagnosing peripheral artery disease (PAD). Although the ABI is an objective diagnostic method, it has limited reliability in certain scenarios. The aim of the present study was to determine the accuracy and reliability of the toe brachial index (TBI) as a diagnostic tool for detecting stenosis in PAD, associated with normal or low ABI values.MethodsABI and TBI values were measured in 15 patients with diabetic gangrene who were suspected of having lower extremity arterial insufficiency. The ABI and TBI values were measured using a device that allowed the simultaneous measurement of systolic blood pressure in the upper and lower extremities. In addition, the ABI and TBI values were compared pre- and post-angiography.ResultsPatients with an ABI of 0.9-1.3 showed almost no difference between the 2 measurements. The patients with TBI >0.6 had no arterial insufficiency. The patients with TBI <0.6 required vascular intervention with ballooning. After the angiography, the gangrenous wounds decreased in size more rapidly than they did prior to the intervention.ConclusionsOur findings suggest that TBI is the method of choice for evaluating lower limb perfusion disorders. This result requires further studies of TBI in a larger number of patients. Future long-term studies should therefore evaluate the utility of TBI as a means of screening for PAD and the present findings should be regarded as preliminary outcomes.

Obesity-induced chronic low-grade inflammation, in particular in adipose tissue, contributes to the development of insulin resistance and type 2 diabetes. However, the mechanism by which obesity induces adipose tissue inflammation has not been completely elucidated. Recent studies suggest that alteration of the nuclear lamina is associated with age-associated chronic inflammation in humans and fly. These findings led us to investigate whether the nuclear lamina regulates obesity-mediated chronic inflammation. In this study, we show that lamin A/C mediates inflammation in macrophages. The gene and protein expression levels of lamin A/C are significantly increased in epididymal adipose tissues from obese rodent models and omental fat from obese human subjects compared to their lean controls. Flow cytometry and gene expression analyses reveal that the protein and gene expression levels of lamin A/C are increased in adipose tissue macrophages (ATMs) by obesity. We further show that ectopic overexpression of lamin A/C in macrophages spontaneously activates NF-κB, and increases the gene expression levels of proinflammatory genes, such as Il6, Tnf, Ccl2, and Nos2. Conversely, deletion of lamin A/C in macrophages reduces LPS-induced expression of these proinflammatory genes. Importantly, we find that myeloid cell-specific lamin A/C deficiency ameliorates obesity-induced insulin resistance and adipose tissue inflammation. Thus, our data suggest that lamin A/C mediates the activation of ATM inflammation by regulating NF-κB, thereby contributing to the development of obesity-induced insulin resistance.

The corrosion behavior of Al foil as the current collector for lithium-ion batteries is studied by linear-sweep thermammetry. The onset temperature for Al pitting corrosion depends on Li salt that is dissolved in an ionic liquid solvent; lithium bis͑trifluo-romethanesulfonyl͒imide ͑LiTFSI͒ Ͻ lithium bis͑perfluoroethanesulfonyl͒imide ͑LiBETI͒ Ͻ LiPF 6 Ͻ LiBF 4 . With LiBF 4 , no corrosion current is observed until 110°C. X-ray photoelectron spectroscopy study reveals that this Al surface is covered by Al-F compound ͑presumably AlF 3 ͒. Due to the formation of a highly passivating AlF 3 layer in this electrolyte, the high voltage LiNi 0.5 Mn 1.5 O 4 positive electrode coated on Al foil can be successfully cycled at 65°C without electrode failure.One of the recent issues in lithium-ion batteries ͑LIBs͒ is, among others, the cell life that is deeply associated with the thermal stability of the cell constituents. An occasional high temperature exposure causes a thermal degradation of electrode/electrolyte materials, leading to a shortened cell life. In this sense, the room-temperature ionic liquids ͑RTILs͒ that have a superior thermal stability to the organic solvents have been projected as the solvent for long-lived LIBs. [1][2][3][4] For RTILs to be used as the solvent for thermally stable ͑therefore, long-lived͒ LIBs, however, they should also be inert to the corrosion of Al foil that is used as the current collector for the positive electrodes of LIBs. That is, the breakdown of the native oxide ͑Al 2 O 3 ͒ upon high temperature exposure, which passivates the Al surface in a normal condition, can lead to cell failure. 5 The corrosion/passivation behavior of bis͑trifluoromethane-sulfonyl͒imide ͑TFSI͒ anion was reported. 6,7 When LiTFSI is dissolved in organic solvents, the anion attacks the native Al 2 O 3 to generate Al-TFSI compounds that is soluble in organic solvents to lead Al corrosion. In ionic liquid solvents, however, Al corrosion is greatly reduced because the Al-TFSI compounds are insoluble in ionic liquids. 8,9 The literatures on the corrosion behavior of RTILs at either ambient temperature or elevated temperatures are still quite limited. In this work, the RTIL ͓propylmethylpyrrolidinium ͑PMPyr͒-TFSI͔ effectively passivates an Al surface up to 5.0 V ͑vs Li/Li + ͒ at room temperature, but its protection becomes poorer at elevated temperatures. The selection of appropriate Li salt ͑LiBF 4 ͒, however, improves the passivation behavior even at elevated temperatures. ExperimentalThe used PMPyr-TFSI was prepared according to the previous report. 10 Coin-type cells ͑2032 size, Hohsen͒ were assembled with an Al foil electrode ͑Donghae, Ͼ99.85%, 20 m thick͒, a glass filter separator ͑Advantec, GA-55, 0.21 mm thick, 0.6 m pore͒, lithium metal foil ͑Cyprus͒, and an electrolyte. The Al working electrodes were prepared to be 1.1 cm in diameter and exposed to the electrolyte side in a cell. The electrolytes were prepared by dissolving 1.0 M lithium salts ͓LiTFSI ͑3M͒, LiBETI ͑Chemtall͒, LiPF 6 ͑Aldrich͒, and LiBF 4 ͑...

To prepare chitosan-based polymeric amphiphiles that can form nanosized core-shell structures (nanoparticles) in aqueous milieu, chitosan oligosaccharides (COSs) were modified chemically with hydrophobic cholesterol groups. The physicochemical properties of the hydrophobized COSs (COSCs) were investigated by using dynamic light scattering and fluorescence spectroscopy. The feasibility of applying the COSCs to biomedical applications was investigated by introducing them into a gene delivery system. The COSCs formed nanosized self-aggregates in aqueous environments. Furthermore, the physicochemical properties of the COSC nanoparticles were closely related to the molecular weights of the COSs and the number of hydrophobic groups per COS chain. The critical aggregation concentration values decreased upon increasing the hydrophobicity of the COSCs. The COSCs efficiently condensed plasmid DNA into nanosized ion-complexes, in contrast to the effect of the unmodified COSs. An investigation of gene condensation, performed using a gel retardation assay, revealed that COS6(M n = 6,040 Da) containing 5% of cholesteryl chloroformate (COS6C5) formed a stable DNA complex at a COS6C5/DNA weight ratio of 2. In contrast, COS6, the unmodified COS, failed to form a stable COS/DNA complex even at an elevated weight ratio of 8. Furthermore, the COS6C5/DNA complex enhanced the in vitro transfection efficiency on Human embryonic kidney 293 cells by over 100 and 3 times those of COS6 and poly(L-lysine), respectively. Therefore, hydrophobized chitosan oligosaccharide can be considered as an efficient gene carrier for gene delivery systems.

We herein present our experience with microsurgical training using a porcine thigh infusion model, which resembles living animal models. The main femoral artery was cannulated with a 24G angioneedle and fixed with 4-0 black silk sutures. Microanastomoses were performed on the femoral vessels of porcine thighs using end-to-end and end-to-side techniques. During the microanastomoses, dyed 0.9% isotonic sodium chloride was infused at 200 to 850 mL/min using an infusion pump. No anastomosis site leakage was observed and the patency of the anastomosis site was maintained. We consider the porcine thigh infusion model to be appropriate for the beginner trainee because the large vessel size enables him or her to practice. In addition, our model provides a circulation environment similar to the in vivo human environment. We believe that our model is more convenient than living animal models and more accurate than models that do not provide a circulation environment.

Most glioblastomas frequently recur at sites of radiotherapy, but it is unclear if changes in the tumor microenvironment due to radiotherapy influence glioblastoma recurrence. Here, we demonstrate that radiation-induced senescent glioblastoma cells exhibit a senescence-associated secretory phenotype that functions through NFκB signaling to influence changes in the tumor microenvironment, such as recruitment of Ly6G+ inflammatory cells and vessel formation. In particular, Ly6G+ cells promote conversion of glioblastoma cells to glioblastoma stem cells (GSCs) through the NOS2-NO-ID4 regulatory axis. Specific inhibition of NFκB signaling in irradiated glioma cells using the IκBα super repressor prevents changes in the tumor microenvironment and dedifferentiation of glioblastoma cells. Treatment with Ly6G-neutralizing antibodies also reduces the number of GSCs and prolongs survival in tumor-bearing mice after radiotherapy. Clinically, a positive correlation exists between Ly6G+ cells and the NOS2-NO-ID4 regulatory axis in patients diagnosed with recurrent glioblastoma. Together, our results illustrate important roles for Ly6G+ inflammatory cells recruited by radiation-induced SASP in cancer cell dedifferentiation and tumor recurrence.

Porcine circovirus type 2 (PCV2) is the primary causative agent of postweaning multisystemic wasting syndrome, which leads to serious economic losses in the pig industry worldwide. While the molecular basis of PCV2 replication and pathogenicity remains elusive, it is increasingly apparent that the microRNA (miRNA) pathway plays a key role in controlling virus-host interactions, in addition to a wide range of cellular processes. Here, we employed Solexa deep sequencing technology to determine which cellular miRNAs were differentially regulated after expression of each of three PCV2-encoded open reading frames (ORFs) in porcine kidney epithelial (PK15) cells. We identified 51 ORF1-regulated miRNAs, 74 ORF2-regulated miRNAs, and 32 ORF3-regulated miRNAs that differed in abundance compared to the control. Gene ontology analysis of the putative targets of these miRNAs identified transcriptional regulation as the most significantly enriched biological process, while KEGG pathway analysis revealed significant enrichment for several pathways including MAPK signaling, which is activated during PCV2 infection. Among the potential target genes of ORF-regulated miRNAs, two genes encoding proteins that are known to interact with PCV2-encoded proteins, zinc finger protein 265 (ZNF265) and regulator of G protein signaling 16 (RGS16), were selected for further analysis. We provide evidence that ZNF265 and RGS16 are direct targets of miR-139-5p and let-7e, respectively, which are both down-regulated by ORF2. Our data will initiate further studies to elucidate the roles of ORF-regulated cellular miRNAs in PCV2-host interactions.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-015-0172-5) contains supplementary material, which is available to authorized users.