No abstract

Abstract3,3′-Diindolylmethane (DIM), a natural acid condensation extracted from cruciferous plants, exhibits anti-fibrotic effects in hepatic and cardiac fibrosis models. The effects of DIM on renal fibrosis, however, are unclear. This study aimed to explore the protective effects of DIM on renal fibrosis. Unilateral ureteral obstruction (UUO) and transforming growth factor (TGF)-β1-stimulated normal rat kidney (NRK)-49F fibroblast cell mouse models were established. The models were then treated with DIM for the assessment of its anti-fibrotic effects and mechanisms. Results of HE and Masson staining showed that DIM reduced kidney injury and production of interstitial collagens fibrosis. CTS also inhibited expression of fibronectin, collagen-1 but retain E-cadherin in the UUO model. Furthermore, DIM suppressed local fibroblast activation, as evidenced by the suppressed expression of the myofibroblast markers α-SMA and vimentin in vivo and in vitro. In addition, DIM significantly inhibited the TGF-β1-induced proliferation of NRK49F cells in a time- and dose-dependent manner. DIM decreased Smad2/3 phosphorylation but increased Smad7 expression. Results suggested that DIM inhibits TGF-β/Smad2/3 signaling to attenuate renal interstitial fibrosis via inhibiting local fibroblast activation. This mechanism is likely related to Smad7 induction.

CAR-T cell therapy has demonstrated encouraging therapeutic effects when treating haematological malignancies. 1,2 Two CAR-T treatments targeting CD19 have been launched successfully. 3,4 CAR-T targeting the B-cell maturation antigen (BCMA) has also shown positive therapeutic effects in clinical trials. [5][6][7] However, CAR-T cell therapy has not yet had similar results in solid tumours. [8][9][10] Solid tumours have a more complex immunosuppressive microenvironment and there are many immunosuppressive cells and cytokines which inhibit the activation and survival of CAR-T cells within the tumour. 11,12 The dense extracellular matrix (ECM) also prevents CAR-T cells from infiltrating into solid tumours and can affect CAR-T cell activity. 13,14 During cultivation, additional cytokines, such as IL7 and IL15, can promote the effective proliferation and maintenance of the memory phenotype of CAR-T cells. 15,16 However, adding extra IL-7 during cultivation has no effect in vivo. It is difficult for T cells, including CAR-T cells, to penetrate the extracellular matrix and thus infiltrate the tumour. 13,14 Reports suggest that recombinant hyaluronidase rHPH20

Aim. Recombinant human trefoil factor 3 (intestinal trefoil factor) has been suggested to be partially protective against necrotizing enterocolitis (NEC), but the mechanisms of this protection have not been defined. We investigated whether the protective effects of rhTFF3 are the result of an anti-inflammatory response. Methods. The rats were killed on day 4, the distal ileum was harvested for morphological studies and immunohistochemistry for NF-κB (p65), and the amounts of IL-1β, IL-6, and IL-10 in the intestinal tissue were measured using commercial ELISA assay kits. Results. In the neonatal NEC, IL-1β, IL-6, and IL-10 were significantly higher than in normal group. In normal group, IL-1β and IL-6 were significantly decreased, and the amount of IL-10 was markedly increased compared with NEC group. In the NEC model, immunohistochemical staining for NF-κB (p65) was demonstrated to be of a strong brown color and was distributed in the intestinal epithelium. Treatment with rhTFF3 significantly decreased the immunoreactivity of NF-κB (p65) in the NEC model. Conclusions. Intestinal inflammation was ameliorated after rhTFF3 was injected. rhTFF3 may protect against the intestinal injury of the neonatal rat NEC model by suppression of the inflammatory response.

ITF may provide a new way for the therapy of NEC in rats.