Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-β(TGF-β).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated his-topathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mecha-nism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

Objective:To transfer the interleukin 37 (IL-37) gene to cervical cancer Hela cells,and to explore the killing effect of IL-37 on the HeLa cells and its enhancement in the chemotherapy sensitivity of HeLa cells.Methods:The pIRES2-EGFP (NC group) and pIRES2-EGFP/IL-37 (IL-37 group) plasmids were transfected into the HeLa cells.Q-PCR and Western blotting methods were used to detect the expression levels of IL-37 mRNA and protein.The activities of HeLa cells in NC group,IL-37 group,DDP group and IL-37+DDP group were detected by CCK8 method,and the inhibitory rates of cells were calculated.The gene expressions of signal transducer and activator of transcription 3 (STAT3) and Cyclin D1 were detected by RT-PCR method.Results:Compared with NC group,the expression levels of IL-37 mRNA and protein in IL-37 group were significantly increased (P＜0.01).The activities of HeLa cells in DDP (5-15 mg · L-1) groups were inhibited after administration for 24-72 h (P＜ 0.01);the inhibitory rates in IL-37 + DDP group were higher than those in DDP group within 48 h after administration (P＜0.05).Compared with IL-37 group,the inhibitory rates in IL-37+DDP group was increased with 96 h after administration (P＜0.05).Compared with NC group,the expression levels of STAT3 and Cyclin D1 mRNA in IL-37 group were significantly decreased (P＜0.01).Conclusion:The over-expression of IL-37 can inhibit the proliferation of cervical cancer cells and enhance the effect of DDP on the chemotherapy of cervical cancer cells which may be related to the down-regulation of the expressions of STAT3 and Cyclin D1 by IL-37.

ObjectiveTo investigate the effect of shikosin （SHI） on psoriasis （PSO） and explore the underlying mechanism via the cyclic guanosine monophosphate-adenosine monophosphate synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodHaCaT cells were classified into normal culture（Control）， a mixture of five proinflammatory cytokines（M5）， low-， medium-， and high-dose SHI （L-SHI， M-SHI， and H-SHI， respectively）， and SHI+ADU-S100 groups. The cells in the M5 group were stimulated with 10 μg·L^-1 interleukin （IL）-1α， IL-17， IL-22， tumor necrosis factor （TNF）-α， and oncostatin M （OSM） for 48 h. The cells in the L-SHI， M-SHI， and H-SHI groups were treated with 0.1， 1， 10 μmol·L^-1 SHI， respectively， on the basis of the treatment in the M5 group. The cells in the SHI+ADU-S100 group were treated with 10 μmol·L^-1 STING activator ADU-S100 on the basis of the treatment in the H-SHI group. The methyl thiazolyl tetrazolium （MTT） assay and colony formation assay were employed to examine the effect of SHI on the proliferation of HaCaT cells. The wound healing assay was employed to examine the effect of SHI on the migration of HaCaT cells. Flow cytometry was employed to detect the effect of SHI on the apoptosis of HaCaT cells. Enzyme-linked immunosorbent assay was employed to measure the levels of IL-1β， IL-6， IL-15， IL-23， and interferon-γ （IFN-γ） in HaCaT cells. Western blot was employed to determine the protein levels of cGAS and STING in HaCaT cells. ResultCompared with Control group， the M5 group showed decreased survival rate， colony formation， and would healing rate of HaCaT cells， increased apoptosis rate， elevated levels of IL-1β， IL-6， IL-15， IL-23， and IFN-γ， and up-regulated protein levels of cGAS and STING （P<0.01）. Compared with the M5 group， the L-SHI， M-SHI， and H-SHI groups showed increased survival rate， cell colony formation， and wound healing rate， decreased apoptosis rate， lowered levels of IL-1β， IL-6， IL-15， IL-23， and IFN-γ， and down-regulated protein levels of cGAS and STING （P<0.01）. Compared with the H-SHI group， the SHI+ADU-S100 group showed decreased survival rate， cell colony formation， and wound healing rate， increased apoptosis rate， risen levels of IL-1β， IL-6， IL-15， IL-23， and IFN-γ， and up-regulated protein levels of cGAS and STING （P<0.01）. ConclusionSHI can inhibit the inflammation in the cell model of PSO by inhibiting the cGAS/STING signaling pathway.