Lipid and carbohydrate modifications of α-galactosylcer-amide differently influence mouse and human type I natural killer T cell activation

The ability of different glycosphingolipids (GSLs) to activate type I natural killer T cells (NKT cells) has been known for 2 decades. The possible therapeutic use of these GSLs has been studied in many ways; however, studies are needed in which the efficacy of promising GSLs is compared under identical conditions. Here, we compare five unique GSLs structurally derived from alpha-galactosylceramide. We employed biophysical and biological assays, as well as x-ray crystallography to study the impact of the chemical modifications of the antigen on type I NKT cell activation. Although all glycolipids are bound by the T cell receptor of type I NKT cells in real time binding assays with high affinity, only a few activate type INKT cells in in vivo or in vitro experiments. The differences in biological responses are likely a result of different pharmacokinetic properties of each lipid, which carry modifications at different parts of the molecule. Our results indicate a need to perform a variety of assays to ascertain the therapeutic potential of type I NKT cell GSL activators

To assess surgical outcomes of combined femtosecond laser-assisted cataract surgery with 25-gauge vitrectomy surgery at a tertiary eye care center

Background: The aim of this study was to assess the surgical outcomes of combined femtosecond laser-assisted cataract surgery (FLACS) with 25-gauge vitrectomy surgery. Materials and Methods: A retrospective analysis of 45 patients who underwent combined FLACS with 25-gauge vitrectomy surgery. Results: A total number of 45 eyes of 45 patients were treated with a mean age of 63.27 years (range 45-75). The mean follow-up was 3 months (range 3-12 months). The mean preoperative best-corrected visual acuity was 1.47 ± 0.86. The mean postoperative vision was 0.36 ± 0.36 and 0.275 ± 0.184 at a paired t-test revealed a statistically significant improvement in visual acuity at 1 month (P < 0.001) and 3 months (P < 0.001). The most common indication for surgery was full-thickness macular hole (51.1%), vitreous hemorrhage (24.4%), followed by epiretinal membrane (17.7%) and rhegmatogenous retinal detachment (4.4%). Conclusion: Combining FLACS with vitrectomy may be a step toward achieving better outcomes when combined CS and vitrectomy is performed

Selective Conditions Are Required for the Induction of Invariant NKT Cell Hyporesponsiveness by Antigenic Stimulation

Activation of invariant (i) NKT cells with the model Ag alpha-galactosylceramide induces rapid production of multiple cytokines, impacting a wide variety of different immune reactions. In contrast, following secondary activation with a-galactosylceramide, the behavior of iNKT cells is altered for months, with the production of most cytokines being strongly reduced. The requirements for the induction of this hyporesponsive state, however, remain poorly defined. In this study, we show that Th1-biasing iNKT cell Ags could induce iNKT cell hyporesponsiveness, as long as a minimum antigenic affinity was reached. In contrast, the Th2-biasing Ag OCH did not induce a hyporesponsive state, nor did cytokine-driven iNKT cell activation by LPS or infections. Furthermore, although dendritic cells and B cells have been reported to be essential for iNKT cell stimulation, neither dendritic cells nor B cells were required to induce iNKT cell hyporesponsiveness. Therefore, our data indicate that whereas some bone marrow-derived cells could induce iNKT cell hyporesponsiveness, selective conditions, dependent on the structure and potency of the Ag, were required to induce hyporesponsiveness

Pt-Catalyzed Rearrangement of Oxaspirohexanes to 3‑Methylenetetrahydrofurans: Scope and Mechanism

A novel Pt-catalyzed rearrangement of oxaspirohexanes to 3-methylenetetrahydrofurans is reported. Mechanistic studies by ¹³C-labeling experiments confirm oxidative addition of Pt­(II) regioselectively to the least substituted carbon–carbon bond of the cyclopropane to form a platinacyclobutane intermediate. To our knowledge, this is the first alkoxy-substituted platinacyclobutane that has been observed spectroscopically. The scope and a proposed mechanism of this new Pt-catalyzed transformation are described

Selective Conditions Are Required for the Induction of Invariant NKT Cell Hyporesponsiveness by Antigenic Stimulation

Activation of invariant natural killer T (iNKT) cells with the model antigen α-galactosylceramide (αGalCer) induces rapid production of multiple cytokines, impacting a wide variety of different immune reactions. In contrast, following secondary activation with αGalCer, the behavior of iNKT cells is altered for months, with the production of most cytokines being strongly reduced. The requirements for the induction of this hypo-responsive state, however, remain poorly defined. Here, we show that Th1-biasing iNKT cell antigens could induce iNKT cell hypo-responsiveness, as long as a minimum antigenic affinity was reached. In contrast, the Th2-biasing antigen OCH did not induce a hypo-responsive state, nor did cytokine-driven iNKT cell activation by LPS or infections. Furthermore, while DCs and B cells have been reported to be essential for iNKT cell stimulation, neither DCs nor B cells were required to induce iNKT cell hypo-responsiveness. Therefore, our data indicate that while some bone marrow-derived cells could induce iNKT cell hypo-responsiveness, selective conditions, dependent on the structure and potency of the antigen, were required to induce hypo-responsiveness

Pt-Catalyzed Rearrangement of Oxaspirohexanes to 3‑Methylenetetrahydrofurans: Scope and Mechanism

A novel Pt-catalyzed rearrangement of oxaspirohexanes to 3-methylenetetrahydrofurans is reported. Mechanistic studies by ¹³C-labeling experiments confirm oxidative addition of Pt­(II) regioselectively to the least substituted carbon–carbon bond of the cyclopropane to form a platinacyclobutane intermediate. To our knowledge, this is the first alkoxy-substituted platinacyclobutane that has been observed spectroscopically. The scope and a proposed mechanism of this new Pt-catalyzed transformation are described

Asymmetric Synthesis of Sulfinamides Using (−)-Quinine as Chiral Auxiliary

A process has been designed and demonstrated for the asymmetric synthesis of sulfinamides using quinine as auxiliary. A variety of chiral sulfinamides including <i>N</i>-alkyl sulfinamides with diverse structure were prepared in good yields and excellent enantioselectivity starting from easily available and inexpensive reagents. The auxiliary quinine could be recovered and recycled