[Objective]To investigate the effect and mechanism of Soufeng Jiedu Decoction on cisplatin-induced acute kidney injury.[Methods]Forty C57BL/6J mice were randomly divided into 5 groups,8 mice in each group:control group and model group were gavaged with distilled water,positive control group was gavaged with prednisolone 5 mg/(kg·d),Soufeng Jiedu Decoction low and high dose groups were gavaged with Soufeng Jiedu Decoction 300 and 500 mg/(kg·d)respectively.These drugs were administered continuously for 10 days.On the 7th day of administration,mice in model group,positive control group,Soufeng Jiedu Decoction low dose group,and Soufeng Jiedu Decoction high dose group were intraperitoneally injected with 20 mg·kg-1 cisplatin,while the control group received an equivalent volume of 0.9%sodium chloride solution.Biochemical approaches were utilized to measure the levels of blood urea nitrogen(BUN),serum creatinine(SCr),malondialdehyde(MDA),and the activity of superoxide dismutase(SOD)and catalase(CAT).Kidney tissue pathological morphology was assessed using hematoxylin-eosin(HE)staining in all groups.Real time-quantitative polymerase chain reaction(RT-qPCR)was employed to determine the gene expressions of kidney injury molecule-1(Kim-1),neutrophil gelatinase-associated lipocalin(Ngal),quinone oxidoreductase 1(Nqo1)and glutamate cysteine ligase(Gclm)in the kidney of mice.Western blot analysis was conducted to evaluate the protein expressions of nuclear factor erythroid 2-related factor 2(NRF2),heme oxygenase-1(HO-1),p62,microtubule-associated protein light chain 3(LC3B)and phosphorylated-AMP-activated protein kinase(p-AMPK).[Results]Compared with control group,model group exhibited a significant increase in levels of BUN and SCr,as well as upregulation of Kim-1 and Ngal gene expression(P<0.01).Notably,severe kidney injury was observed in model group,characterized by tubular degeneration,edema,necrosis,cystic dilatation with focal hemorrhage.Moreover,model group exhibited a significant increase in MDA levels,accompanied by a notable decrease in CAT and SOD activities(P<0.01).On the other hand,model group displayed elevated expressions of renal Nqo1 and Gclm genes,as well as increased protein expressions of NRF2,HO-1,and LC3B,while the protein expressions of p62 and p-AMPK were significantly reduced(P<0.01).Compared with model group,treatment with Soufeng Jiedu Decoction resulted in a significant reduction in BUN and SCr levels,as well as suppression of Kim-1 and Ngal gene expression in the kidney of mice.Furthermore,Soufeng Jiedu Decoction ameliorated acute kidney injury-associated renal tissue lesions.Treatment with Soufeng Jiedu Decoction also led to a decrease in MDA levels,and an increase in CAT and SOD activities within the kidney.Additionally,Soufeng Jiedu Decoction promoted the expression of Nqo1 and Gclm genes,as well as the protein expressions of NRF2,HO-1,LC3B and p-AMPK,while inhibiting the expression of p62 protein(P<0.01).[Conclusion]Soufeng Jiedu Decoction effectively alleviates cisplatin-induced acute kidney injury possibly by inhibiting oxidative stress and promoting autophagy in the kidney.

Objective : To elucidate the effect of phosphorylation modification at the threonine 592 (Thr592) site on the inhibition of gastric cancer proliferation by sterile alpha motifs and HD structural domain－containing protein 1 (SAMHD1) and the potential mechanism of action． Methods: Post-translational modifications (PTMs) of SAMHD1 protein in gastric cancer tissues and cell lines in the database were analyzed，and immunohistochemical stai- ning was performed to detect SAMHD1 Thr592 phosphorylation in paired tissues of gastric cancer patients．In gastric cancer cells，SAMHD1 Thr592 variants were constructed and transiently transfected，and cell proliferation was detected using the cell counting kit 8 ( CCK-8 ) method． The phosphorylation of the cyclin-dependent kinases ( CDK) 2 protein threonine 160 (Thr160) site was inhibited by the addition of different concentrations of the CDK6 inhibitor，Palbociclib，which reduced the level of SAMHD1 protein Thr592 phosphorylation．Three online databases were used to analyze the SAMHD1 reciprocal proteins and take the intersection to derive the Nik-related kinase (NRK) protein．Immunoprecipitation ( Co-IP) ，mass spectrometry and Western blot were used to verify the interactions between SAMHD1 and NRK proteins and detect the effect of NRK on the phosphorylation of the SAMHD1 Thr592 site. Results : Compared with PTMs such as ubiquitination，the highest level of phosphorylation modification of SAMHD1 was observed in tumors，and the difference was statistically significant (P＜0. 01) ．Immunohistochemical experiments showed that phosphorylated SAMHD1 (Thr592) was expressed higher in gastric adenocarcinoma than that in normal mucosal tissue adjacent to the cancer，and the difference was statistically significant (P < 0. 01) ．Western blot assay showed that SAMHD1 protein expression was elevated in MKN-45 cells in the overexpression wild type and mutant groups ，and phosphorylated SAMHD1 levels were also elevated in the wild type， T592E and HD / AA groups． CCK-8 assay showed that both SAMHD1 wild type and T592A could inhibit gastric cancer cell proliferation，while T592E and HD / AA had no effect on gastric cancer proliferation． On the basis of overexpression of SAMHD1，CCK-8 suggested that cell proliferation was inhibited after adding different concentrations of Palbociclib treatment，and Western blot assay suggested that the phosphorylation level was also reduced. NRK protein was obtained by Co-IP and mass spectrometry identification to screen the SAMHD1 reciprocal protein profile and database intersection，and NRK was found to interact with SAMHD1 protein and promote phosphorylation at SAMHD1 Thr592 site by Co-IP and Western blot assay． Conclusion Phosphorylation of the Thr592 site contributes to the loss of SAMHD1 's ability to inhibit gastric cancer cell proliferation，which is reversed by Palbociclib．NRK interacts with SAMHD1 protein，promoting phosphorylation of the SAMHD1 Thr592 site.

Aim To explore the effects of curcumin on inflammatory reaction and blood-brain barrier permeability in rats following cerebral ischemic injury,and to further investigate its potential mechanisms.Methods SD rats underwent the cerebral ischemia/reperfusion injury by the sutrure occlusion model were randomly divided into sham-control,cerebral ischemia and curcumin-treatment groups.Neurological deficit scores,cerebral infarction volume,brain water content and blood-brain barrier (BBB) permeability were measured,myeloperoxidase(MPO)activities in rat brain were measured as an index of neutrophil infiltration;content of tumor necrosis factor-α(TNF-α)in rat brain was detected by ELISA;expression of matrix metalloproteinase-9(MMP-9) in rat brain was determined by Western blot.Results Neurological deficit and cerebral infarction volume was decreased in curcumin-treatment group.The degree of neutrophilicgranulo cyte infiltration in cerebral tissues was decreased and the integrity of BBB was improved.Curcumin could also inhibit TNF-α and MMP-9 expression.Conclusion Curcumin exerts the neuroprotective effect on cerebral ischemia/reperfusion injury in rats through inhibiting the inflammatory reaction and improving BBB integrity,which may be associated with the inhibiton of TNF-α and MMP-9.