NR4A1 silencing alleviates high-glucose-stimulated HK-2 cells pyroptosis and fibrosis via hindering NLRP3 activation and PI3K/AKT pathway

BACKGROUND The pathophysiology of diabetic kidney disease(DKD)is complex.Interfering with the processes of pyroptosis and fibrosis is an effective strategy for slowing DKD progression.Previous studies have revealed that nuclear receptor subfamily 4 group A member 1(NR4A1)may serve as a novel pathogenic element in DKD;however,the specific mechanism by which it contributes to pyroptosis and fibrosis in DKD is unknown.AIM To investigate the role of NR4A1 in renal pyroptosis and fibrosis in DKD and possible molecular mechanisms.METHODS Streptozotocin 60 mg/kg was injected intraperitoneally to establish a rat model of DKD.Typically,45 mmol/L glucose[high glucose(HG)]was used to activate HK-2 cells to mimic the DKD model in vitro.HK-2 cells were transfected with NR4A1 siRNA to silence NR4A1.RESULTS NR4A1 was elevated in renal tissues of DKD rats and HG-stimulated HK-2 cells.Concurrently,NOD-like receptor protein 3(NLRP3)and phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)pathways were triggered,and pyroptosis and expression of fibrosis-linked elements was increased in vivo and in vitro.These alterations were significantly reversed via NR4A1 silencing.CONCLUSION Inhibition of NR4A1 mitigated pyroptosis and fibrosis via suppressing NLRP3 activation and the PI3K/AKT pathway in HG-activated HK-2 cells.

Latamoxef-induced severe thrombocytopenia during the treatment of pulmonary infection:A case report

BACKGROUND Latamoxef shows excellent antibacterial activity against anaerobic bacteria such as Bacteroides fragilis.Reports of thrombocytopenic toxicity of latamoxef are limited.This report presents a case of severe thrombocytopenia possibly induced by latamoxef,an infrequent adverse drug reaction in a young patient with tuberculosis and Crohn's disease in China.CASE SUMMARY We reported a case of severe thrombocytopenia induced by latamoxef in a 28-year-old man with tuberculosis and Crohn's disease.On admission,the patient presented with a cough productive of bloody sputum,a chest computed tomogram suggested scattered mottled,high-density shadows in both lungs.Laboratory tests indicated a platelet count of 140000/μL.Considered a pulmonary bacterial infection,the patient received anti-infection therapy with latamoxef(dose:2.0 g)intravenously Q12h.On the 9th day of treatment,the platelet count decreased to 44000/μL.On the 12th day,scattered purpura and ecchymosis appeared on the patient’s limbs and trunk,and the platelet count decreased to 9000/μL after latamoxef treatment for 15 d.Three days after discontinuation of latamoxef,the platelet count recovered to 157000/μL,and the area of scattered purpura and ecchymosis on the limbs and trunk decreased.The platelet counts remained in the normal range,and no thrombocytopenia was found at follow-up 15 mo after discharge.CONCLUSION For patients treated with latamoxef,platelet counts should be carefully followed,and caregivers should be vigilant for the appearance of scattered ecchymosis.