Pam3CSK4 enhanced beta cell loss and diabetogenesis: The roles of IFN-gamma and IL-17

Toll like receptors are primary sensors of both innate and adaptive immune systems. They activate APCs and influence T-cell function in inflammatory autoimmune response. Studies have shown that TLR manipulation may lead to either tolerance or trigger autoimmunity. Using diabetogenic and subdiabetogenic multiple low doses of streptozotocin, we demonstrate here that Pam3 CYS-CK₄ a TLR-2 agonist, enhances and promotes diabetes in C57BL/6 male mice following increased apoptosis of β islet cells. FACS analysis of isolated pancreatic lymph node cells revealed significant increased number of macrophages, dendritic cells, CD4⁺ TNF-α⁺, CD4⁺ IFN-γ⁺ and most significantly, CD4⁺ IL-17⁺ and reduced number of CD25⁺Fox p3⁺ T cells after Pam3CSK₄ treatment. Genetic deletion of IFN-γ prevents whereas deletion of IL-17 reduced severity of Pam3CSK₄-induced enhancement of diabetes. TLR-2 agonist-enhanced diabetogenesis is also influenced by enhanced influx of antigen presenting cells and suppression of regulatory T cell activity.     

Correction: The β-cyclodextrin-modified nanosized ZSM-5 zeolite as a carrier for curcumin

Correction for ‘The β-cyclodextrin-modified nanosized ZSM-5 zeolite as a carrier for curcumin’ by Shahin Amani et al., RSC Adv., 2019, 9, 32348–32356, DOI: 10.1039/C9RA04739E.

The authors regret that the names of the authors were listed incorrectly in the original article. The corrected author list is as shown above.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Serum measures of iron status and HFE gene mutations in patients with hepatitis B virus infection

Aim: We tested associations between HFE mutations and hepatitis B virus (HBV) infection. We also explored measures of total body iron status and their association with chronic HBV infection. Methods: Serum measures of iron status and HFE mutations (C282Y, H63D, and S65C) were assessed in 344 Iranian patients with chronic HBV infection (214 asymptomatic carriers, 130 patients with chronic progressive liver disease [CPLD]) and 302 controls. Results: Frequencies of HFE mutations did not differ between patients with chronic HBV infection and controls (C282Y: P=0.9, H63D: P= 0.8, S65C: P=0.9). By logistic regression, advanced hepatic fibrosis was associated with HFE H63D mutation (OR=13.1, P=0.006; 95% CI=2.0-84.1). Higher levels of serum ferritin and transferrin saturation were observed in patients with CPLD than in healthy controls (P=0.0001 and 0.01, respectively, adjusted for age and sex). None of the serum iron measures was related to liver fibrosis stage or necroinflammatory grade. Conclusion: Serum iron measures are associated with chronic progressive hepatitis B. Carriage of HFE mutations is not associated with the presence of chronic HBV infection or values of serum iron measures in this population, although HFE H63D is associated with more advanced hepatic fibrosis.     

Endothelium and NOTCH specify and amplify aorta-gonad-mesonephros–derived hematopoietic stem cells

Hematopoietic stem cells (HSCs) first emerge during embryonic development within vessels such as the dorsal aorta of the aorta-gonad-mesonephros (AGM) region, suggesting that signals from the vascular microenvironment are critical for HSC development. Here, we demonstrated that AGM-derived endothelial cells (ECs) engineered to constitutively express AKT (AGM AKT-ECs) can provide an in vitro niche that recapitulates embryonic HSC specification and amplification. Specifically, nonengrafting embryonic precursors, including the VE-cadherin–expressing population that lacks hematopoietic surface markers, cocultured with AGM AKT-ECs specified into long-term, adult-engrafting HSCs, establishing that a vascular niche is sufficient to induce the endothelial-to-HSC transition in vitro. Subsequent to hematopoietic induction, coculture with AGM AKT-ECs also substantially increased the numbers of HSCs derived from VE-cadherin⁺CD45⁺ AGM hematopoietic cells, consistent with a role in supporting further HSC maturation and self-renewal. We also identified conditions that included NOTCH activation with an immobilized NOTCH ligand that were sufficient to amplify AGM-derived HSCs following their specification in the absence of AGM AKT-ECs. Together, these studies begin to define the critical niche components and resident signals required for HSC induction and self-renewal ex vivo, and thus provide insight for development of defined in vitro systems targeted toward HSC generation for therapeutic applications.     

The β-cyclodextrin-modified nanosized ZSM-5 zeolite as a carrier for curcumin

Herein, the nanosized ZSM-5 zeolite was synthesized based on a fractional factorial experimental design by a hydrothermal method to study the optimum conditions for the synthesis and formation of the ZSM-5 zeolite by employing different conditions. The samples were synthesized without any organic template, and different conditions, such as the molar composition of the synthesis gel and reaction time, were applied in a wide range. Then, the samples were analysed by X-ray diffraction to investigate the formation of the zeolite ZSM-5, and the results were compared to obtain the optimum conditions for its synthesis. The obtained samples were characterized by SEM, FTIR spectroscopy and TGA. Then, the functionalization of nano zeolite ZSM-5 crystals with β-cyclodextrin (β-CD) was investigated. The zeolite surface was first functionalized with amino groups using an amino alkoxysilane. Then, toluene diisocyanate was reacted with the amino-terminated ZSM-5 zeolite crystals and used for the incorporation of β-CD via its remaining isocyanate groups. After this, a drug delivery system (DDS) was prepared based on the cyclodextrin-modified zeolite with the curcumin anticancer drug, and its formation was studied under experimental conditions. The results of in vitro studies show that this drug delivery system has better characteristics than free curcumin in terms of stability and anti-proliferative and anti-inflammatory effects.

Herein, the nanosized ZSM-5 zeolite was synthesized based on a fractional factorial experimental design by a hydrothermal method to study the optimum conditions for the synthesis and formation of the ZSM-5 zeolite by employing different conditions.