An insect sclerotization-inspired antifouling armor on biomedical devices combats thrombosis and embedding.

Thrombus formation and tissue embedding significantly impair the clinical efficacy and retrievability of temporary interventional medical devices. Herein, we report an insect sclerotization-inspired antifouling armor for tailoring temporary interventional devices with durable resistance to protein adsorption and the following protein-mediated complications. By mimicking the phenol-polyamine chemistry assisted by phenol oxidases during sclerotization, we develop a facile one-step method to crosslink bovine serum albumin (BSA) with oxidized hydrocaffeic acid (HCA), resulting in a stable and universal BSA@HCA armor. Furthermore, the surface of the BSA@HCA armor, enriched with carboxyl groups, supports the secondary grafting of polyethylene glycol (PEG), further enhancing both its antifouling performance and durability. The synergy of robustly immobilized BSA and covalently grafted PEG provide potent resistance to the adhesion of proteins, platelets, and vascular cells in vitro. In ex vivo blood circulation experiment, the armored surface reduces thrombus formation by 95 %. Moreover, the antifouling armor retained over 60 % of its fouling resistance after 28 days of immersion in PBS. Overall, our armor engineering strategy presents a promising solution for enhancing the antifouling properties and clinical performance of temporary interventional medical devices.

FGF21 attenuates high uric acid­induced endoplasmic reticulum stress, inflammation and vascular endothelial cell dysfunction by activating Sirt1.

Uric acid (UA) is the final oxidation product of purine metabolism. Hyperuricemia has been previously reported to contribute to vascular endothelial dysfunction and the development of cardiovascular diseases, metabolic syndrome and chronic kidney diseases. In addition, it has been reported that fibroblast growth factor 21 (FGF21) can exert regulatory effects on UA­induced lipid accumulation. Therefore, the present study aimed to investigate the possible role of FGF21 in HUVEC cell injury induced by UA. The study used UA to induce HUVEC cell injury, inhibited sirtuin 1 (Sirt1) expression using EX527 and overexpressed FGF21 by transfection. Subsequently, reverse transcription­quantitative PCR was performed to measure the mRNA expression levels of FGF21, Sirt1 and inflammatory cytokines TNF­α, IL­1ß and IL­6, whereas western blotting was performed to measure their corresponding protein expression levels including FGF21, Sirt1, NLR family pyrin domain containing 3, pro­caspase1, apoptosis­associated speck­like protein containing a CARD, activating transcription factor 4, C/EBP homologous protein and eukaryotic initiation factor 2. Furthermore, dichloro­dihydro­fluorescein diacetate staining was performed to measure intracellular reactive oxygen species (ROS) generation in HUVECs. The levels of ROS and nitric oxide were also quantified using commercial assay kits. The results demonstrated that overexpression of FGF21 significantly inhibited UA treatment­induced endoplasmic reticulum (ER) stress, inflammation and oxidative stress in HUVECs. Furthermore, overexpression of FGF21 significantly activated Sirt1. The sirt1 inhibitor, EX527, significantly abrogated the suppressive effects of FGF21 overexpression on ER stress, inflammation and oxidative stress in UA­stimulated HUVECs. To conclude, results of the present study suggested that FGF21 may attenuate UA­induced ER stress, inflammation and vascular endothelial cell dysfunction by activating Sirt1. Therefore, FGF21 may be a potential effective target for the future treatment of vascular endothelial cell dysfunction.

The protective effect of hydrogen-rich water on rats with type 2 diabetes mellitus.

The hydrogen-rich water (HW) has been reported to possess a beneficial role in patients with diabetes. However, a systemic evaluation with an appropriate animal model is necessary to reveal its mechanisms and efficacy. Herein, the protective effects of drinking HW on lipid and glucose metabolism, oxidative stress, and inflammation in type 2 diabetes mellitus (T2DM) rats were investigated. The well-modeled T2DM rats (induced by high-fat diet combined with low-dose streptozotocin (STZ) injection) were divided into two groups (n ≥ 15 of each): fed a high-fat diet and drinking distilled water or HW at a constant concentration above 1.0 ppm; normal rats were used as control group (n ≥ 10): fed a regular diet and drinking distilled water. Several biomarkers of lipid and glucose metabolism, oxidative stress ,and inflammation were evaluated after drinking distilled water or HW for 3 weeks. The effect of HW on liver, kidney, and spleen of T2DM rats was also analyzed by HE and Oil Red O staining. The results showed that drinking HW suppressed the increase in glucose, total cholesterol, oxidative stress, and inflammation. Moreover, HW also ameliorates hyperglycemia-induced liver, kidney, and spleen dysfunction. Overall, this study indicates that patients with T2DM may be able to improve their condition by supplementing HW as daily drinking water.

Leflunomide monotherapy versus combination therapy with conventional synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis: a retrospective study.

Leflunomide (LEF) is a conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for the treatment of rheumatoid arthritis. However, there are few reports on the comparison of efficacy between LEF alone and combined with other csDMARDs. Here, the efficacy and safety of LEF monotherapy (88) and combination (361) therapy groups were evaluated. After 3 months, there were no significant differences in 28-joint disease activity score (DAS28), health assessment questionnaire (HAQ), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) between the monotherapy and combination groups (all P > 0.05). According to the European League Against Rheumatism (EULAR) response criteria, it was found that the DAS28 response rates were similar in the two groups (P > 0.05). Besides, the two groups presented similar safety profiles. Subgroup analysis found that there was no difference in efficacy among the three combined therapies (LEF + methotrexate (MTX), LEF + hydroxychloroquine (HCQ), and LEF + MTX + HCQ) and LEF monotherapy. Furthermore, when the dose of LEF was less than 40 mg/day, no significant difference in efficacy was observed between low and high doses. Overall, these results indicated that low dose LEF monotherapy was not inferior to the combination therapy.

Survival analysis of late-onset systemic lupus erythematosus: a cohort study in China.

The aim of this study is to explore the survival rate and risk factors of mortality in patients with late-onset systemic lupus erythematosus (SLE) in a large cohort. Clinical presentations, disease activity, organ damage scores, autoantibody profile, and mortality data were obtained retrospectively from late-onset SLE patients (onset age ≥50 years) diagnosed between 1995 and 2009. The risk factors of organ damage were evaluated by the chi-square test and logistic regression. The cumulative rate of survival was calculated by Kaplan-Meier method, and factors predictive of mortality were studied by Cox proportion hazard regression model. A total of 158 patients (132 female and 26 male) were studied. The average onset age was 58.66 ± 6.38 years and mean disease duration was 63.85 ± 48.17 months. One hundred and four patients had organ damage at the time of data analysis. Hematological system and kidney involvement were most common. Central nervous system involvement was relatively rare. In univariate logistic analysis, associations were found between SLE disease activity index (SLEDAI) at diagnosis (OR = 1.133, P = 0.001); renal involvement (OR = 2.441, P = 0.009) and edema (OR = 2.812, P = 0.003) were associated with organ damage. And SLEDAI at diagnosis (OR = 1.103, P = 0.034) was independent factor for organ damage in multivariate logistic regression. During the follow-up, 64 patients (51 female and 13 male) died. Five-, 10-, and 15-year survival rates were 80.4, 56.5, and 31.7 %, respectively. Median survival time was 123 months. The analysis of Cox proportion hazard regression model showed that age at disease onset (OR = 1.069, P = 0.002), compliance of medical care (OR = 3.282, P = 0.001), and SLEDAI at diagnosis (OR = 1.091, P = 0.003) were independent risk factors of mortality. Late-onset SLE has a poor long-term prognosis. Infection is the major cause of death in patients with late-onset lupus. Disease activity, medical care, and onset age are strongly related to death of late-onset SLE.