3-O-trans-caffeoyloleanolic acid (COA) is a pentacyclic triterpenoid compound, with significant anti-inflammatory effects. In this study, we report the protective effects of COA on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explored its mechanism of action. LPS was used to construct in vivo mouse ALI models to observe the effects of COA pretreatment on lung pathology, inflammation, and oxidative stress. In vitro, mouse alveolar macrophages MH-S cells were cultured and stimulated with LPS to investigate the effects of COA pretreatment on inflammation and oxidative stress. Western blotting was used to investigate the expression of iNOS, TLR4, p-p65, p-AKT, and p-PI3K from in vivo and in vitro samples. The results showed that COA significantly improved lung injury, inhibited neutrophil infiltration, prevented macrophage infiltration, inhibited the release of inflammatory factors, reduced oxidative stress, and down-regulated the expression of iNOS, TLR4, p-p65, p-AKT, and p-PI3K in ALI mice caused by LPS. In vitro, COA inhibited the release of inflammatory factors, reduced oxidative stress, and down-regulated the expression of iNOS, TLR4, p-p65, p-AKT, and p-PI3K in MH-S cells stimulated with LPS. Of interest, the protective effects of COA were significantly attenuated in MH-S cells pretreated with the PI3K phosphopeptide activator 740Y-P with no effect on TLR4 expression observed. Taken together, these findings confirm the protective effects of COA on ALI. We further demonstrate that the anti-inflammation and antioxidant effects of COA are mediated through its effects on PI3K/AKT and potentially TLR4.To describe the 10-year outcomes of islet transplantation within the Swiss-French GRAGIL Network, in patients with type 1 diabetes experiencing high glucose variability associated with severe hypoglycemia and/or with functional kidney graft. We conducted a retrospective analysis of all subjects transplanted in the GRAGIL-1c and GARGIL-2 islet transplantation trials and analyzed components of metabolic control, graft function and safety outcomes over the 10-year period of follow-up. PD173212 research buy Forty-four patients were included between September 2003 and April 2010. Thirty-one patients completed a ten-year follow-up. Ten years after islet transplantation, median HbA1c was 7.2% [6.2-8.0] (55 mmol/mol [44-64]) vs 8.0% [7.1-9.1] (64 mmol/mol [54-76]) before transplantation (p less then 0.001). 17/23 (73.9%) recipients were free of severe hypoglycemia, 1/21 patient (4.8%) was insulin-independent and median C-peptide was 0.6 ng/ml [0.2-1.2]. Insulin requirements (UI/kg/day) were 0.3 [0.1-0.5] vs 0.5 [0.4-0.6] before transplantation (p less then 0.001). Median [IQR] β-score was 1 [0-4] (p less then 0.05 when comparing with pre-transplantation values) and 51.9% recipients had a functional islet graft at 10 years. With a 10-year follow up in a multicentric network, islet transplantation provided sustained improvement of glycemic control and was efficient to prevent severe hypoglycemia in almost 75% of the recipients.The exact duration of viable SARS-CoV-2 shedding in kidney transplant recipients (KTRs) remains unclear. Here, we retrospectively investigated this issue using cell cultures of SARS-CoV-2 RT-PCR-positive nasopharyngeal samples (n = 40) obtained from 16 KTRs with symptomatic COVID-19 up to 39 days from symptom onset. A length of viable SARS-CoV-2 shedding >3 weeks from the onset of symptoms was identified in four KTRs (25%). These results suggest that a significant proportion of KTRs can shed viable SARS-CoV-2 for at least 3 weeks, which may favor the emergence of new variants. Based on these data, we recommend prolonging the isolation of KTRs with COVID-19 until negative SARS-CoV-2 RT-PCR testing.

To evaluate and analyze the potential relationship between periosteal reaction and medial compartment knee osteoarthritis (KOA), and to assess the independent risk factors for the development of periosteal reaction associated with medial compartment KOA.

This is a retrospective comparative study. From January 2019 to December 2019 at the Third Hospital of Hebei Medical University, a total of 363 patients (726 knees) with medial compartment KOA were enrolled in this study according to our inclusion and exclusion criteria, including 91 males and 272 females, with an mean age of 57.9 ± 12.8 years (range, 18-82 years). Among these patients, 206 patients (412 knees) were allocated to the periosteal reaction group (44 males and 162 females) and 157 patients (314 knees) were allocated to the non-periosteal reaction group (47 males and 110 females). The classification of KOA severity was based on Kellgren and Lawrence (K-L) grading system. The malalignment of the lower extremities in coronal plane was evaluated a, which occurred most commonly adjacent to the lateral of proximal tibia diaphysis, and thus we concluded that periosteal reaction may be an anatomical adaptation for medial compartment KOA based upon these results.Periplocin, as one of the components of cardiac glycosides in Cortex periplocae, exhibited cardiotonic effects. Orally ingesting periplocin in high doses or over prolonged periods would cause serious adverse reactions, especially cardiotoxicity, which limits the applications of periplocin in clinical therapy. It has been reported that Panax notoginseng saponins could be used in compatibility with periplocin to reduce the cardiotoxicity of periplocin. To clarify the mechanisms of periplocin-induced cardiotoxicity and compatibility-pairing in reducing cardiotoxicity, the gas chromatography-mass spectrometry method was used to detect and analyze the metabolic profiles of rat plasma and urine samples after oral administration of periplocin, Panax notoginseng saponins, and the different compatibility ratios of periplocin and Panax notoginseng saponins. The multivariate statistical analysis method was used to screen and identify the biomarkers. A total of 49 potential biomarkers (28 in plasma and 21 in urine) associated with periplocin-induced cardiotoxicity were identified. Seven pathways were found through metabolomic pathway analysis. Moreover, the levels of 42 biomarkers (22 in plasma and 20 in urine) were close to normal after compatibility pairing. By analyzing the relative metabolic pathways, Panax notoginseng saponins could effectively reduce the cardiotoxicity of periplocin by affecting the tricarboxylic acid cycle, energy metabolism, and arachidonic acid metabolism.