Radiation-induced thrombocytopenia (RIT) faces a perplexing challenge in the clinical treatment of cancer patients, and current therapeutic approaches are inadequate in the clinical settings. In this research, oxymatrine, a new molecule capable of healing RIT was screened out, and the underlying regulatory mechanism associated with magakaryocyte (MK) differentiation and thrombopoiesis was demonstrated. The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro. The ability to induce thrombopoiesis was subsequently demonstrated in Tg (cd41:enhanced green fluorescent protein (eGFP)) zebrafish and RIT model mice. In addition, we carried out network pharmacological prediction, drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) analyses to explore the potential targets of oxymatrine. Moreover, the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Western blot (WB), and immunofluorescence. Oxymatrine markedly promoted MK differentiation and maturation in vitro. Moreover, oxymatrine induced thrombopoiesis in Tg (cd41:eGFP) zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice. Mechanistically, oxymatrine directly binds to toll-like receptor 2 (TLR2) and further regulates the downstream pathway stimulator of interferon genes (STING)/nuclear factor-kappaB (NF-κB), which can be blocked by C29 and C-176, which are specific inhibitors of TLR2 and STING, respectively. Taken together, we demonstrated that oxymatrine, a novel TLR2 agonist, plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis, suggesting that oxymatrine is a promising candidate for RIT therapy.

Autoimmune Diseases ; Diastole ; Humans ; Uric Acid ; Ventricular Dysfunction, Left ; Ventricular Function, Left

Aim To investigate the role of Wnt/β-cate-nin signaling pathway on the baicalin-induced osteo-genic differentiation in rat bone marrow derived mesen-chymal stem cells ( rBMSC ) . Methods rBMSC was isolated and cultured by adherence screening method. Alkaline phosphatase ( ALP) amount, CFU-FALP and mineralized nodules were compared between each ba-icalin group and vehicle control group at different time points. Real time q-PCR was employed to evaluate the mRNA level of Wnt signaling-related marker ( Wnt10a, GSK-3β,β-catenin and LEF1) after baica-lin treatment. Protein expression of β-catenin and Runx2 was measured by Western blot. Results Ba-icalin significantly increased ALP activities from day 3 to day 7 . The formation of CFU-FALP and mineralized nodules remarkably increased after rBMSC was treated with1, 10, 50 μmol · L-1 baicalin. mRNA levels of Wnt10a, β-catenin, GSK-3β, LEF1and osteocalcin were enhanced significantly in baicalin-treated group compared to control group. Protein expression of β-catenin and Runx2 was also elevated. Conclusion Baicalin ( 0. 1 to 50 μmol · L-1 ) promotes the osteo-genic differentiation and maturation of rBMSC, in which Wnt/β-catenin signaling pathway might be in-volved.

Objective To summarize the various acute abdomen manifestation of systemic lupus erythematosus (SLE) and their diagnosis and treatment.Methods Twenty SLE patients with AA were analysed and 35 year′s literature was reviewed.Results Most AA were of active SLE (70%),others were of non SLE related disease (30%).Cause of these cases was diversified,which often lead to misdiagnosis.Making correct diagnosis as early as possible was the key point to improve the patient′s survival rate.Conclusion SLE with AA indicates a critical condition.Investigating the cause of AA and working out appropriate treatment measures are most important.

Objective To explore the diagnostic significance of anti-cyclic citrullinated peptide antibody(anti-CCP)and the role it plays in the articular erosion in patients with rheumatoid arthritis(RA).Methods The diagnostic significance of anti-CCP?AKA and RF were evaluated respectively.Seventy-five RA patients were devided into group1(limited radiographic damage group)and group2(severe radiographic damage group).The distribution of anti-CCP,AKA and RF in patients of the two groups were investigated.A univariate analysis was used to determine whether anti-CCP?AKA?RF?ANA?ESR?CRP or cutaneous nodules plays a role on articular erosion in RA.To determine which has the best predictive value for severe radiographic da-mage,all variables were entered into a logistic regression model.Results The sensitivity and specificity of an-ti-CCP?AKA and RF were49%,94%;50%,93%;79%,67%respectively.When any two markers were combined,the specificity would be raised.The positive rate of these three markers were much higher in group2than that in group1.Anti-CCP had the highest OR(6.71)for articular erosion in RA.Logistic regression analysis showed a strong correlation between anti-CCP,AKA,CRP or cutaneous nodules and less favourable disease outcomes.Cut.aneous nodules had the strongest correlation with severe radiographic damage.Conclusion Anti-CCP is a satisfactory marker for RA.Diagnostic accuracy appears to be raised when anti-CCP combined with AKA and RF.Anti-CCP has a strong correlation with severe radiographic damage.To investigate multiple risk factors of articular erosion will be helpful to pridict the outcome of RA.