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Triptolide (TPL) may mitigate radiation-induced late pulmonary side effects through its inhibition of global pro-inflammatory cytokines. In this study, we evaluated the effect of TPL in C57BL/6 mice, the animals were exposed to radiation with vehicle (15 Gy), radiation with TPL (0.25 mg/kg i.v., twice weekly for 1, 2 and 3 months), radiation and celecoxib (CLX) (30 mg/kg) and sham irradiation. Cultured supernatant of irradiated RAW 264.7 and MLE-15 cells and lung lysate in different groups were enzyme-linked immunosorbent assays at 33 h. Respiratory rate, pulmonary compliance and pulmonary density were measured at 5 months in all groups. The groups exposed to radiation with vehicle and radiation with TPL exhibited significant differences in respiratory rate and pulmonary compliance (480 ± 75/min vs. 378 ± 76/min; 0.6 ± 0.1 ml/cm H2O/p kg vs. 0.9 ± 0.2 ml/cm H2O/p kg). Seventeen cytokines were significantly reduced in the lung lysate of the radiation exposure with TPL group at 5 months compared to that of the radiation with vehicle group, including profibrotic cytokines implicated in pulmonary fibrosis, such as IL-1β, TGF- β1 and IL-13. The radiation exposure with TPL mice exhibited a 41% reduction of pulmonary density and a 25% reduction of hydroxyproline in the lung, compared to that of radiation with vehicle mice. The trichrome-stained area of fibrotic foci and pathological scaling in sections of the mice treated with radiation and TPL mice were significantly less than those of the radiation with vehicle-treated group. In addition, the radiation with TPL-treated mice exhibited a trend of improved survival rate compared to that of the radiation with vehicle-treated mice at 5 months (83% vs. 53%). Three radiation-induced profibrotic cytokines in the radiation with vehicle-treated group were significantly reduced by TPL treatment, and this partly contributed to the trend of improved survival rate and pulmonary density and function and the decreased severity of pulmonary fibrosis at 5 months. Our findings indicate that TPL could be a potential new agent to mitigate radiation-induced pulmonary fibrosis.

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Purpose Epidermal keratinocytes, which can be severely damaged after ionizing radiation (IR), are rapid turnover cells that function as a barrier protecting the host from pathogenic invasion and fluid loss. We tested fibroblast growth factor-peptide (FGF-P), a small peptide derived from the receptor-binding domain of FGF-2, as a potential mitigator of radiation effects via proliferation and the barrier function of keratinocytes. Methods and Materials Keratinocytes isolated from neonatal foreskin were grown on transwells. After 0, 5, or 10-Gy, the cells were treated with a vehicle or FGF-P. The permeability of IR cells was assessed through transepithelial electrical resistance (TEER) and a paracellular tracer flux of fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA) with Ussing chambers. The cell proliferation was measured with yellow tetrazolium salt (MTT) and tritiated thymidine (3H-TdR) assays. The phosphorylation of extracellular signal-regulated kinases (ERK) was measured in an enzyme-linked immunosorbent (ELISA)-like assay, and the proteins related to tight junctions (TJ) and adherens junctions (AJ) were examined with Western blotting. We used a mouse model to assess the ability of FGF-P to promote the healing of skin β-burns created with a strontium applicator. Results 1) FGF-P reduced the permeability of irradiated keratinocytes, as evidenced by increased TEER and decreased diffusion of FITC-BSA both associated with the regulation of different proteins and levels of TJ and AJ; 2) FGF-P enhanced the proliferation of irradiated keratinocytes, as evidenced by increased MTT activity and 3H-TdR incorporation, which was associated with activation of the ERK pathway; and 3) FGF-P promoted the healing of skin β-burns. Conclusions FGF-P enhances the barrier function, including up-regulation of TJ proteins, increases proliferation of human keratinocytes, and accelerates the healing of skin β-burns. FGF-P is a promising mitigator that improves the proliferation and barrier function of keratinocytes after IR.

In order to obtain high-strength and high-ductility Al–Si–Cu–Mg alloys, the present research is focused on optimizing the composition of soluble phases, the structure and morphology of insoluble phases, and artificial ageing processes. The results show that the best matches, 0.4 wt% Mg and 1.2 wt% Cu in the Al–9Si alloy, avoided the toxic effect of the blocky Al2Cu on the mechanical properties of the alloy. The addition of 0.6 wt% Zn modified the morphology of eutectic Si from coarse particles to fine fibrous particles and the texture of Fe-rich phases from acicular β-Fe to blocky π-Fe in the Al–9Si–1.2Cu–0.4Mg-based alloy. With the optimization of the heat treatment parameters, the spherical eutectic Si and the fully fused β-Fe dramatically improved the ultimate tensile strength and elongation to fracture. Compared with the Al–9Si–1.2Cu–0.4Mg-based alloy, the 0.6 wt% Zn modified alloy not only increased the ultimate tensile strength and elongation to fracture of peak ageing but also reduced the time of peak ageing. The following improved combination of higher tensile strength and higher elongation was achieved for 0.6 wt% Zn modified alloy by double-stage ageing: 100 °C × 3 h + 180 °C × 7 h, with mechanical properties of ultimate tensile strength (UTS) of ~371 MPa, yield strength (YS) of ~291 MPa, and elongation to fracture (E%) of ~5.6%.