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Meliasanines A-L, twelve previously unreported tirucallane-type triterpenoids, together with fifteen known ones, have been isolated from the stem bark of Melia toosendan. Their structures and absolute configurations were determined based on HRESIMS, and NMR, combined with calculated ECD and single-crystal X-ray diffraction analyses. Subsequently, all compounds except 10 were evaluated for their inhibitory effect on the production of nitric oxide induced by lipopolysaccharide in RAW264.7 macrophage cells. The results indicated that seven compounds (1, 13, 14, 16, 20, 22, and 23) exhibited significant NO inhibitory effects, with IC 50 values ranging from 1.35 to 5.93 μM, which were more effective than the positive control indomethacin (IC 50  = 13.18 μM). Moreover, the corresponding results of Western blot analysis revealed that meliasanine A (1) can significantly suppress the protein expression of inducible nitric oxide synthase and cyclooxygenase 2 in a concentration-dependent manner. The mechanism study suggested that meliasanine A exerts an anti-inflammatory effect via the nuclear factor-κB signaling pathway by suppressing phosphorylation of P65 and IκBα., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to evaluate the efficacy of decitabine (DAC) and identify factors influencing treatment responses in patients with primary immune thrombocytopenia (ITP) who had failed glucocorticoid therapy. Methods: Clinical data of 61 patients with glucocorticoid-resistant ITP who received DAC therapy (5 mg·m(-2)·d(-1)×3 d via intravenous infusion) for at least three cycles with 3-4-week intervals at the Department of Hematology, Qilu Hospital of Shandong University, from November 2015 to June 2021 were analyzed retrospectively. Results: The 61 patients comprised 20 males and 41 females, with a median age of 45 years (range: 15-81 years). Among them, 43 patients were glucocorticoid-dependent (glucocorticoid-dependent group), while 18 patients were glucocorticoid-resistant (glucocorticoid-resistant group). Following DAC treatment, 12 patients (19.67% ) achieved complete response (CR), and 16 patients (26.23% ) exhibited response (R), resulting in an overall response (OR) rate of 45.90% (28/61). Comparison between the OR group ( n =28) and the non-response (NR) group ( n =33) revealed significant differences in responses to glucocorticoids (dependent or resistant) and platelet counts before treatment ( χ (2)=8.789, P =0.003; z =-2.416, P =0.016). The glucocorticoid-dependent group showed higher platelet counts than the glucocorticoid-resistant group after the second and third cycles of DAC treatment ( P =0.032, 0.024). Moreover, the OR rates after the first, second, and third cycles of DAC treatment in the glucocorticoid-dependent group were all higher than those in the glucocorticoid-resistant group ( P =0.042, P =0.012, P =0.029). A significant correlation was observed between glucocorticoid dependence and responses to DAC treatment ( OR =9.213, 95% CI 1.937-43.820, P =0.005) . Conclusion: DAC demonstrates definitive efficacy with mild adverse effects in a subset of patients with glucocorticoid-resistant primary ITP. Glucocorticoid dependence and higher platelet counts before treatment are associated with a favorable response to DAC therapy.

Extracellular signal-regulated kinase 1/2 (ERK1/2) is a serine/threoninekinase involved in the signal transduction cascade of Ras-Raf-mitogen-activated protein kinase (MEK)-ERK.It participates in the cell growth,proliferation and even invasion by regulating gene transcription and expression.The occurrence of a variety of diseases such as lung cancer,liver cancer,ovarian cancer,cervical cancer,endometriosis,and preeclampsia,as well the metastasis and disease progression,is closely associated with the regulation of cell invasion by ERK1/2 signaling pathway.Therefore,exploring the regulation of ERK1/2 signaling on cell invasion and its role in pathogenesis of diseases may help to develop more effective treatment schemes.This article introduces recent progress in the regulation of ERK1/2 signaling on cell invasion and the role of such regulation in diseases,with a view to give new insights into the clinical treatment of ERK 1/2-related diseases.

Objective: To investigate the effects of DUSP1 on the hippocampal injury of young rats with epilepsy (EP) through mediating ERK1/2 signaling pathway., Methods: Young SD rats were selected and divided into Control, EP, EP + LV-GFP, EP + LV-DUSP1, EP + LV-siDUSP1, and EP + LV-siDUSP1 + U0126 groups. Morris Water Maze Test was used to detect the spatial learning and memory. Nissl staining and TUNEL staining were conducted and the inflammatory factors and oxidative stress-related indicators were also measured. Western blotting was utilized to detect the expression of DUSP1 and ERK1/2 pathway. EP cell model was constructed in vitro to verify the in vivo results., Results: Compared with Control group, young rats in EP group had decreased spatial learning and memory abilities and increased apoptotic rate and decreased number of Nissl positive cells. Besides, the up-regulated levels in inflammatory factors (IL-1β, IL-6), MDA content, and p-ERK1/2/ERK1/2 protein expression, as well as the down-regulated levels in DUSP1 protein expression and SOD content were also observed in EP rats. The EP rats treated with LV-DUSP1 showed obvious improvements regarding the above indicators, while those treated with LV-siDUSP1 had aggravated injury. But the effect of LV-siDUSP1 can be reversed by the treatment with ERK1/2 pathway inhibitor U0126. Further in vitro investigation verified the in vivo results., Conclusion: DUSP1 may ameliorate the oxidative stress and inflammatory injury, as well as improve spatial learning and memory abilities via inhibiting ERK1/2 pathway, eventually playing protective roles in hippocampal injury of young rats with EP., (Copyright © 2021 Elsevier B.V. All rights reserved.)