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The present study aims to study the effect of vitamin D (Vit D) or / and coconut oil (Coc) on the splenic histological changes of diabetic adult mice induced by STZ. The mice were divided into 7 groups, and the experimental duration was 4 weeks. GpI: control group without any treatments; GpII&GpIII: non-diabetic groups orally received Vit D in a dose of 500 IU (6.25 ml)/kg b.w/d or Coc in a dose of 7.5 ml /kg b.w/d; GpIV: diabetic group injected i.p. with a single dose of STZ (200 mg/kg bw); Gps V,VI &VII: administration of Vit D or Coc or both together to diabetic group. The results recorded: GpII&GpIII no significant changes in the blood glucose (BG), insulin&splenic weight levels. GpIV had a significant increase in BG, significant decrease in insulin & splenic weight values. GpV recorded a modest decrease in BG, and a modest rise in insulin & a marked splenic weight atrophy; while GpVI or GpVII registered a marked decrease in BG, a rise in insulin levels & a marked splenic weight increment. Histologically, the splenic sections of control or non-diabetic mice received either Vit D or Coc demonstrated normal structure of the splenocytes. GpIV showed great numbers of giant cells, disarrangement and interference of red and white pulps, and dilated congested blood vessels. Little improvement was seen in GpV while GpVI or GpVII showed a marked improvement in the splenic tissues. In conclusion, diabetic mice received either Coc or co-dministered with Vit D demonstrated strong anti-hyperglycemic effects to recovery the glucose and insulin rates to typical levels, and restored the splenic weight and histological architecture to normal status than those given Vit D alone.

Background: Anti-cancer adoptive T cell therapy has shown significant anti-tumor responses in cancer patients. This therapy is based on in vitro activation of autologous T cells harvested from a cancer patient and infusing them back through blood. The efficacy of adoptively transferred T cells depends on the in vitro conditioning regimen in particular the type of used cytokines. Aim: This study aimed to use toll like receptors (TLRs) ligands (TLRLs) to condition T cells in vitro as a novel approach instead of cytokines. Methods: Spleen cells were harvested from TCR transgenic C57BL/6 pmel-1 mice, in which CD8+ T cells are engineered to recognize melanoma MHC class-I peptides.Unfractionated splenocytes were cultured for 24 hours in vitro with media or melaoma peptide plus or minus IL-12 (10ng/ml), poly(I:C) (TLR3L; 25ug/ml) or CpG (TLR9L; 10ug/ml). Then, activation, proliferation and cytokine production of the cultured cells were assessed. In another set of experiments, the cultured cells were harvested and infused into syngeneic B6 mice followed by vaccination to evaluate their antigen-specific expansion and contraction. Results: Conditioning of donor splenocytes in vitro with the TLR3L or TLR9L during antigen stimulation increased the antigen specific activation, proliferation, and cytokine production. Interestingly, in vitro treatment of the unfractionated splenocytes with TLR9L enhanced the activation and proliferation of B cells regardless antigen stimulation. Adoptive transfer of TLRL-conditioned peptide stimulated CD8+ T cells into naïve mice showed better survival and higher expansion in response to concomitant vaccination with peptide. Interestingly, in vitro conditioning of CD8+ T cells with TLR9L and in vivo conditioning with TLR3L resulted in the best antigen specific expansion of these cells upon their adoptive transfer into recipient mice. Conclusion: These results show that provision of CD8+ T cells in vitro and in vivo with certain TLR agonists can markedly enhance their antigen specific responses upon their adoptive transfer, opening a potential application of this approach in anti-cancer adoptive immunotherapy.

Objective: The main objective of this study is to analyze and evaluate the association of IL6-174 G/C gene polymorphisms with response to interleukin-6 blockade in Egyptian patients with systemic juvenile idiopathic arthritis, and to assess the effect of other factors on treatment response as well as long-term efficacy of treatment with Tocilizumab. Methods: Sixty systemic JIA patients (37 males and 23 females with median age at onset 5.2 years) who received IL-6 blockade (Tocilizumab) were recruited. The overall response to treatment with IL-6 blockade was assessed according to: 1) Clinical response, 2) switch (or no switch) to another biological DMARD therapy following IL-6 blockade, 3) achievement of clinically inactive disease within 6 months of IL-6 blockade, 4) improvement in disease activity measured using the modified JADAS-10, and 5) achievement of a glucocorticoid-free state. In addition, basic demographic, laboratory data, characteristics of the disease course and IL6 polymorphisms were assessed.Results: Three IL6 -174 genotypes, including, GG, GC, and CC were found with higher frequencies of GC genotype. These genotypes had non-significant association with the response of sJIA patients to IL-6 blockade in this cohort study. Moreover, a longer time frame from disease onset to diagnosis was associated with poorer long-term treatment response. Conclusion. No significant impact of IL6 -174 G/C gene polymorphisms on treatment response to IL6 blockade therapy in sJIA Egyptian patients, providing evidence of a “window of opportunity” for improved long-term treatment response with shorter time from the disease onset to diagnosis.

Background: Epithelial-mesenchymal transition (EMT) is a critical event in wound healing and tissue repair following injury. Transforming growth factor beta-1 (TGFβ1) plays an important role in inducing EMT in lung epithelial cells in vitro and in vivo. As fibroblast growth factor-2 (FGF2) reverses TGFβ1-induced collagen I (COL1A1) and α-smooth muscle actin (Actin alpha 2; ACTA2) expression in primary mouse and human lung fibroblasts, we set out this study to determine the effect of FGF2 on TGFβ1-induced EMT in human lung epithelial cells. Methods: BEAS-2B and A549 cells were treated with recombinant FGF2 (2 nM) with or without TGFβ1 (2 ng/ml) for up to 4 days. The phenotypic alterations associated with EMT were assessed by quantitative real-time PCR and E-cadherin protein expression levels was assayed by western blot and immunofluorescence staining. Cell migration was confirmed using wound-healing assay. Results: TGFβ1 treatment led to significantly reduced expression of E-cadherin (CDH1) and markedly induced expression of mesenchymal proteins such as N-cadherin (CDH2), tenascin C (TNC), fibronectin (FN), ACTA2 and COL1A1. TGFβ1 also induced a morphological change and a significant increase in cell migration. FGF2 did not significantly alter EMT gene expression markers on its own, however enhanced TGFβ1-induced suppression of CDH1 and upregulation of ACTA2, but did not alter TNC, FN and CDH2 gene expression levels induced by TGFβ1. FGF2 maintained TGFβ1-induced morphologic changes as well as increased the migration of TGFβ1-treated cells. Furthermore, FGF2 treatment significantly inhibited TGFβ1-induced COL1A1 expression in both BEAS-2B and A549 cells. FGFR-specific tyrosine kinase inhibitor PD173074 blocked the synergism between these two growth factors. Conclusions: This study suggests a synergistic effect between TGFβ1 and FGF2 in inducing EMT, which may play an important role in wound healing and tissue repair after injury. Our findings provide insight into the effects of FGF2 following lung injury and in pulmonary fibrosis.