Sh3bp2 Gain-Of-Function Mutation Ameliorates Lupus Phenotypes in B6.MRL-Faslpr Mice

SH3 domain-binding protein 2 (SH3BP2) is an adaptor protein that is predominantly expressed in immune cells, and it regulates intracellular signaling. We had previously reported that a gain-of-function mutation in SH3BP2 exacerbates inflammation and bone loss in murine arthritis models. Here, we explored the involvement of SH3BP2 in a lupus model. Sh3bp2 gain-of-function (P416R knock-in; Sh3bp2KI/+) mice and lupus-prone B6.MRL-Faslpr mice were crossed to yield double-mutant (Sh3bp2KI/+Faslpr/lpr) mice. We monitored survival rates and proteinuria up to 48 weeks of age and assessed renal damage and serum anti-double-stranded DNA antibody levels. Additionally, we analyzed B and T cell subsets in lymphoid tissues by flow cytometry and determined the expression of apoptosis-related molecules in lymph nodes. Sh3bp2 gain-of-function mutation alleviated the poor survival rate, proteinuria, and glomerulosclerosis and significantly reduced serum anti-dsDNA antibody levels in Sh3bp2KI/+Faslpr/lpr mice. Additionally, B220+CD4-CD8- T cell population in lymph nodes was decreased in Sh3bp2KI/+Faslpr/lpr mice, which is possibly associated with the observed increase in cleaved caspase-3 and tumor necrosis factor levels. Sh3bp2 gain-of-function mutation ameliorated clinical and immunological phenotypes in lupus-prone mice. Our findings offer better insight into the unique immunopathological roles of SH3BP2 in autoimmune diseases

Electronic state analysis of Li2RuO3 positive electrode for lithium ion secondary battery

An investigation was made on the electronic structure of 4d transition metal layered oxide material of Li2RuO3 using X-ray photoelectron spectroscopy (XPS) and X-ray absorption spectroscopy (XAS). The intensity of O K pre-edge peak increased for Li ion extracted samples, suggesting increased ligand holes. The Ru 3d XPS spectrum suggested the variation of local structure around Ru ions by extraction of Li ions. We conclude that the delithiation from Li2RuO3 is charge-compensated by O anions, and that the creation of the ligand holes reorganizes electronic structures composed of highly hybridized Ru 4d and O 2p orbitals

Carbon Deposition Assisting the Enhancement of Catalytic Activity with Time-on-Stream in the Dehydrogenation of Isobutane on NiO/Al2O3

In the transformation reaction of alkanes to alkenes via catalytic dehydrogenation, it is generally accepted that the so-called catalytic deactivation behavior will occur. This phenomenon causes a drastic reduction in activity with time-on-stream. It is understood that carbon deposition generated during the reaction then covers the surface of the catalyst, and this leads to a drastic decrease in activity. However, contrary to this common wisdom, our laboratory reported that the dehydrogenation of isobutane to isobutene on NiO/γ-Al2O3 within a specific range of NiO loading in the presence of CO2 actually improved the yield of isobutene with time-on-stream. Since few such cases have been reported, in this study, isobutane was dehydrogenated in the presence of CO2 using NiO/α-Al2O3 as the catalyst with 20% NiO loading and improvement was again observed. In order to investigate the cause of the improvement, both NiO/γ-Al2O3 and NiO/α-Al2O3 with 20% NiO loading were examined in detail following the reaction. According to TEM analysis, both catalysts were covered with a large amount of carbon deposition after the reaction, but there was a difference in the types. The carbon deposition on NiO/γ-Al2O3 had a fibrous nature while that on NiO/α-Al2O3 appeared to be a type of nanowire. Raman spectroscopy revealed that the carbonaceous crystal growth properties of two forms differed depending on the support. In particular, a catalytically active species of metallic nickel was formed in a high degree of dispersion in and on the above two forms of carbon deposition during the reaction, and this resulted in high activity even if the catalyst was covered with a carbon deposition

Femtosecond laser-induced modification at aluminum/diamond interface

We investigated femtosecond-laser-induced modification at an Al/diamond interface. The interface was irradiated from the backside through the diamond substrate, which is transparent to the laser beam. Extremely high pulse energies, i.e., 200 and 100 µJ/pulse, were used to irradiate the interface. The cross-section of the laser-irradiated line was observed with conventional and high-voltage transmission electron microscopy. The modification of the laser-irradiated interface was characterized by the formation of an amorphous phase sandwiched between the deformed Al film and the diamond substrate. The major chemical component of the amorphous phase was identified as carbon, blown from the diamond substrate. The newly formed interface between the amorphous phase and the diamond substrate was concave. In addition, a fine ripple structure with an average spacing one-quarter the wavelength of the laser light was formed only in the sample irradiated by the higher-energy pulses

Effects of HLA-DRB1 alleles on susceptibility and clinical manifestations in Japanese patients with adult onset Still’s disease

BackgroundHLA-DRB1 alleles are major determinants of genetic predisposition to rheumatic diseases. We assessed whether DRB1 alleles are associated with susceptibility to particular clinical features of adult onset Still’s disease (AOSD) in a Japanese population by determining the DRB1 allele distributions.MethodsDRB1 genotyping of 96 patients with AOSD and 1,026 healthy controls was performed. Genomic DNA samples from the AOSD patients were also genotyped for MEFV exons 1, 2, 3, and 10 by direct sequencing.ResultsIn Japanese patients with AOSD, we observed a predisposing association of DRB1*15:01 (p = 8.60 × 10−6, corrected p (Pc) = 0.0002, odds ratio (OR) = 3.04, 95% confidence interval (95% CI) = 1.91–4.84) and DR5 serological group (p = 0.0006, OR = 2.39, 95% CI = 1.49–3.83) and a protective association of DRB1*09:01 (p = 0.0004, Pc = 0.0110, OR = 0.34, 95% CI = 0.18–0.66) with AOSD, and amino acid residues 86 and 98 of the DRβ chain were protectively associated with AOSD. MEFV variants were identified in 49 patients with AOSD (56.3%). The predisposing effect of DR5 was confirmed only in patients with AOSD who had MEFV variants and not in those without MEFV variants. Additionally, DR5 in patients with AOSD are associated with macrophage activation syndrome (MAS) and steroid pulse therapy.ConclusionThe DRB1*15:01 and DR5 are both associated with AOSD susceptibility in Japanese subjects. A protective association between the DRB1*09:01 allele and AOSD was also observed in these patients. Our data also highlight the effects of DRB1 alleles in susceptibility to AOSD

SH3BP2 Deficiency Ameliorates Murine Systemic Lupus Erythematosus

Background: The adaptor protein Src homology 3 domain-binding protein 2 (SH3BP2) is widely expressed in immune cells. It controls intracellular signaling pathways. The present study was undertaken to investigate the role of SH3BP2 in a murine systemic lupus erythematosus model. Methods: For the lupus model, we used Faslpr/lpr mice. Clinical and immunological phenotypes were compared between Faslpr/lpr and SH3BP2-deficient Faslpr/lpr mice. Splenomegaly and renal involvement were assessed. Lymphocyte subsets in the spleen were analyzed by flow cytometry. To examine the role of SH3BP2 in specific cells, B cell-specific SH3BP2-deficient lupus mice were analyzed; T cells and bone marrow-derived dendritic cells and macrophages were analyzed in vitro. Results: SH3BP2 deficiency significantly reduced lupus-like phenotypes, presented as splenomegaly, renal involvement, elevated serum anti-dsDNA antibody, and increased splenic B220+CD4−CD8− T cells. Notably, SH3BP2 deficiency in B cells did not rescue the lupus-like phenotypes. Furthermore, SH3BP2 deficiency did not substantially affect the characteristics of T cells and macrophages in vitro. Interestingly, SH3BP2 deficiency suppressed the differentiation of dendritic cells in vitro and reduced the number of dendritic cells in the spleen of the lupus-prone mice. Conclusions: SH3BP2 deficiency ameliorated lupus-like manifestations. Modulating SH3BP2 expression could thus provide a novel therapeutic approach to autoimmune diseases

Serum amyloid A1 (SAA1) gene polymorphisms in Japanese patients with adult-onset Stillʼs disease

Adult-onset Still\u27s disease (AOSD) is a rare systemic inflammatory disorder in which inflammasome activation plays a pathophysiological role. In view of the inflammatory nature of AOSD, we investigated whether serum amyloid A (SAA) gene polymorphisms affect the susceptibility of patients with AOSD.Eighty-seven Japanese patients with AOSD and 200 healthy Japanese subjects were recruited in this study. The genotypes of the -13C/T SNP in the 5′-flanking region of the SAA1 gene (rs12218) and two SNPs within exon 3 of SAA1 (2995C/T and 3010C/T polymorphisms) were determined using polymerase chain reaction fragment length polymorphism (PCR-RFLP) assay in all subjects. In AOSD patients, exons 1, 2, 3, and 10 of the MEFV gene were also genotyped by direct sequencing.The frequency of the SAA1.3 allele was increased in AOSD patients compared with that in healthy subjects (43.1% versus 37.5%), but the difference was not significant. The −13T allele was more frequently observed in AOSD patients than in healthy subjects (50.6% versus 41.0%, P = .0336). AOSD patients with the −13T allele had been treated with immunosuppressants more frequently than those without this allele. MEFV mutations were detected in 49 patients with AOSD (49/87, 57.3%). AOSD patients with MEFV variants frequently exhibit macrophage activation syndrome, but the difference was not significant (34.7% versus 18.4%, P = .081). Also, there was no significant difference in SAA1 -13C/T allele frequency between AOSD patients with and without MEFV mutations.Our data shows a significant association between T allele of rs12218 and AOSD in Japanese population

Comparison of self‐expandable metallic stent placement followed by laparoscopic resection and elective laparoscopic surgery without stent placement for left‐sided colon cancer.

Aim:Self‐expandable metallic stent (SEMS) placement for obstructive colon cancer is widely performed as a bridge to surgery (BTS) procedure before resection. This study aimed to investigate the surgical and oncological results of laparoscopic elective surgery with or without SEMS placement to assess the efficacy of SEMS placement as a BTS.Methods:We retrospectively analyzed consecutive patients with stage II, III, and IV left‐sided colon cancer who underwent elective laparoscopic resection between 2013 and 2019. All patients were divided into two groups: with and without SEMS placement.Results:The SEMS group included 24 patients, whereas the non‐SEMS group included 86 patients. The serum hemoglobin and albumin levels were lower (P = .049, P = .03), and the serum leukocyte and C‐reactive protein levels were higher (P < .0001, P = .022) in the SEMS group. The tumor diameter and tumor circumferential rate were higher in the SEMS group (both P < .0001). No significant differences were observed in operation time, blood loss, postoperative complications, or postoperative hospital stay. After 1:1 propensity score matching, 15 patients in the SEMS group were compared with 15 patients in the non‐SEMS group. The 3‐year overall survival rates of the SEMS and non‐SEMS groups were 87.5% and 88.9%, respectively (P = .97). The 3‐year recurrence‐free survival rates of the SEMS and non‐SEMS groups were 58.2% and 81.7%, respectively (P = .233). No significant difference was found in the sites of recurrence.Conclusion:The perioperative and long‐term outcomes of SEMS placement as a BTS before laparoscopic resection could be acceptable compared with other elective laparoscopic operations without SEMS placement