Background Endothelial cell inflammation is a central event in the pathogenesis of numerous cardiovascular diseases, including sepsis and atherosclerosis. Triptolide, a principal bioactive ingredient of Traditional Chinese Medicine Tripterygium wilfordii Hook.F., displays anti-inflammatory actions in vivo. However, the mechanisms underlying these beneficial effects remain undetermined. The present study investigated the effects and possible mechanisms of triptolide on lipopolysaccharide (LPS)-induced inflammatory responses in human umbilical vein endothelial cells (HUVECs). Methods The effects of triptolide on the LPS-induced production and expression of inflammatory molecules, monocyte adhesion and activation of nuclear factor (NF)-κB pathway were examined in cultured HUVECs. Results In cultured HUVECs, pre-treatment with triptolide dose-dependently attenuated LPS-induced cytokine and chemokine production, adhesion molecule expression and monocyte adhesion. Mechanistically, triptolide was found to dose-dependently inhibit the LPS-induced increases in the DNA binding activity of NF-κB p65 associated with attenuating IκBα phosphorylation and its degradation. Additionally, the present study revealed that triptolide inhibited LPS-triggered NF-κB transcriptional activation in a dose-dependent manner. Conclusions The results of the present study indicated that triptolide suppresses the inflammatory response of endothelial cells possibly via inhibition of NF-κB activation. Electronic supplementary material The online version of this article (10.1186/s12906-019-2616-3) contains supplementary material, which is available to authorized users.

Studies have demonstrated that microvesicles (MVs) derived from human Wharton's Jelly mesenchymal stromal cells (hWJMSCs) could ameliorate renal ischemia/reperfusion injury (IRI); however, the underlying mechanisms were not clear yet. Here, MVs were isolated and injected intravenously into rats immediately after ischemia of the left kidney, and Erk1/2 activator hepatocyte growth factor (HGF) or inhibitor U0126 was administrated. Tubular cell proliferation and apoptosis were identified by Ki67 or terminal-deoxynucleotidyl transferase-mediated nick end labeling immunostaining. Masson's tri-chrome straining and alpha-smooth muscle actin staining were used for assessing renal fibrosis. The mRNA or protein expression in the kidney was measured by quantitative reverse transcription-PCR or Western blot, respectively. The total collagen concentration was also determined. , NRK-52E cells that treated with MVs under hypoxia injury and with HGF or U0126 administration were used, and cell cycle analysis was performed. The effects of hWJMSC-MVs on enhancing the proliferation and mitigating the apoptosis of renal cells, abrogating IRI-induced fibrosis, improving renal function, decreasing collagen deposition, and altering the expression levels of epithelial-mesenchymal transition and cell cycle-related proteins in IRI rats were found. experiment showed that hWJMSC-MVs could induce G2/M cell cycle arrest and decrease the expression of collagen deposition-related proteins in NRK-52E cells after 24 or 48 h. However, U0126 treatment reversed these effects. In conclusion, MVs derived from hWJMSCs ameliorate IR-induced renal fibrosis by inducing G2/M cell cycle arrest via Erk1/2 signaling.

Background IgA vasculitis (IgAV) is a common small vessel vasculitis in children. Gastrointestinal perforation (GP) rarely presents as a complication of IgAV and is not well characterized. This study is aimed to investigate the clinical features, diagnosis, and risk factors of GP in children with IgAV. Methods We retrospectively reviewed the clinical data of children with IgAV who attended our hospital between January 2014 and June 2018. The clinical risk factors and the corresponding treatments were analyzed for the children with IgAV complication with GP. Results In total, 10,791 children with IgAV were reviewed in this study. GP was observed in 11 children with IgAV, accounted for 0.10% of the total cases. Among those GP patients, 1 case was gastric perforation, 10 cases were intestinal perforation. Five GP cases were identified by abdominal CT. Ultrasonography was failed to detect the occurrence of GP in five cases. The average duration of abdominal pain in the GP cases was 9.3 days, and 9 cases (81.8%) presented with abdominal pain for over 7 days. Gastric/intestinal perforation repair were performed for 3 IgAV GP cases under open surgery. The other eight cases were treated through enterectomy. In comparison with the patients without GP, the GP patients had significant higher rates in the aspect of the abdominal or mixed type of IgAV, abdominal pain duration more than 7 days, hematochezia, renal damage, and methylprednisolone treatment with the daily dosage more than 2 mg/kg. Conclusion GP children accounted for 0.10% of the total IgAV cases. The risk of GP is elevated in IgAV patients who has gastrointestinal symptoms and/or other symptoms such as hematochezia, renal damage, a prolonged abdominal pain (>7 days), administration of methylprednisolone (>2 mg/kg). Abdominal CT is highly recommended for the early detection of GP in IgAV patients. Key messages Gastrointestinal perforation (GP) rarely presents as a complication of IgAV and is not well characterized. 11 out of 10,791 children with IgAV developed GP, accounting for 0.10% of the total number of cases. Abdominal CT is highly recommended for the early detection of GP in IgAV patients.

(1) Background: To investigate the application value of Oxford pathological classification in children with henoch schonlein purpura nephritis (HSPN); (2) Methods: The clinical and pathological data of 341 children with HSPN diagnosed by renal biopsy at the First Affiliated Hospital of Henan University of Traditional Chinese Medicine from January 2015 to December 2017 were retrospectively analysed. Renal pathology was reevaluated and grouped according to the MEST-C score. Therefore, the tubulointerstitial lesions were divided into acute (Ta) and chronic (Tc) groups, M0/M1, E0/E1, S0/S1, Ta0/Ta1, Tc0/Tc1, and C0/C1/C2. The clinical, pathological and prognostic characteristics of the children were analysed by SPSS 23.0; (3) Results: (1) A total of 341 children were included, with a male to female ratio of 1.27:1, a median age of onset of 9 (8,11) years, and 10 (3,21) days between the first symptom and the onset of abnormal urine. (2) Haematuria and proteinuria were the most common clinical subtypes, the proportion of haematuria and proteinuria type was higher in the C1 group, the proportion of nephrotic syndrome type was higher in the M1, E1 and Ta1 groups, and the proportion of chronic nephritis type was higher in the S1 and Tc1 groups (P < 0.05); M1, Ta1, and C2 were associated with more severe microscopic haematuria, and M1, E1, Ta1, and C2 were associated with greater proteinuria (P < 0.05); M1, Ta1 and C1/C2 were associated with the decrease of eGFR and the increase of Scr; M1, E1 and Ta1 were associated with the decrease of ALB, and M1 and C2 were associated with the increase of BUN (P < 0.05). (3) Ⅲ and Ⅱ were the most common pathological changes in ISKDC classification, and there were no Ⅰ, Ⅴ and Ⅵ grade cases; the pathological changes of E1 and C1 were more common with MEST-C score; MEST-C score and ISKDC classification had certain relevance: M1, E1, Ta1 and C2/C1 were more severe in terms of ISKDC classification, and the S1 and Tc1 groups were less severe. (4) In ISKDC grading, IIb had a better prognosis, while IV had a relatively poor prognosis (P < 0.05); Tc1 and C2 were independent prognostic risk factors in the MEST-C score (P < 0.05); (4) Conclusions: (1) The pathological indices of MEST-C were correlated with clinical classification: the proportion of nephrotic syndrome was higher in the M1, E1, and Ta1 groups and chronic glomerulonephritis type in the S1 and Tc1 groups, the pathological changes of M1, Ta1 and C1/C2 were related to the decrease of microscopic haematuria, the level of eGFR and the increase of Scr, and M1, E1, Ta1 and C1/C2 were related to massive proteinuria. (2) All pathological indices of MEST-C were correlated with ISKDC grade; ISKDC grade in the S1 and Tc1 groups was lower than that in the S0 and Tc0 groups; Ta1 lesions were related to C3 deposition intensity; there was a significant difference in prognosis between grade Ⅱ b and grade Ⅳ; M1, Ta1, Tc1 and C2 had relatively poor prognosis, and Tc1 and C2 were related to poor renal prognosis and were independent risk factors for renal prognosis. (3) There is a significant correlation between the MEST-C score and clinical manifestations and laboratory indices of HSPN in children, which can predict the prognosis of the kidney in children with HSPN.

It is widely held that endothelial dysfunction plays a crucial role in various pathological inflammatory conditions. Although triptolide, an active ingredient of Traditional Chinese Medicine Tripterygium wilfordii Hook.F., has been shown to possess anti‐inflammatory effects in vivo, little information is available that describes the effects of triptolide on inflammatory responses in endothelial cells (ECs). In this study, we determined whether triptolide suppresses inflammatory responses of ECs via inhibition of NF‐κB signaling. In human umbilical vein endothelial cells (HUVECs), treatment with lipopolysaccharide (LPS) enhanced cytokine and chemokine production, adhesion molecule expression, and monocyte adhesion. These effects were associated with increased activation of NF‐κB pathway. Furthermore, we found that pretreatment with triptolide dose‐dependently attenuated LPS‐induced actions. Our results indicate that triptolide suppresses the inflammatory responses of ECs via the inhibition of NF‐κB signaling. [This work was supported by the National Natural Science Foundation of China (No. 81673734) and Henan Provincial Science and Technique Foundation for International Cooperation Program (No. 162102410048)].Support or Funding InformationThis work was supported by the National Natural Science Foundation of China (No. 81673734) and Henan Provincial Science and Technique Foundation for International Cooperation Program (No. 162102410048)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.