Jing Wang

Background. Irisin, an exercise-induced myokine and adipocytokine, has been reported to decrease in type 2 diabetic patients. Recently, several research studies indicated that circulating levels were correlated with bone mineral density (BMD). To evaluate bone metabolism, bone turnover markers (BTMs) should be included. However, with respect to newly diagnosed T2DM patients, the relevance of their irisin levels to their BTMs and BMD remains unclear. The investigation of serum irisin levels in patients who have been newly diagnosed with type 2 diabetes and illumination of the relationship between serum irisin levels and those two indices of BMD and BTMs mentioned above are the intention of this cross-sectional study. Methods. 66 new-onset type 2 diabetic patients (T2DM group), together with 82 control subjects (NGT group), were recruited in this study. Serum irisin concentrations and BTMs (including osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), and β-C-terminal telopeptides of type I collagen (β-CTX)) were determined by the enzyme-linked immunosorbent assay (ELISA). Glucose, lipid profile, and insulin were considered as measuring indicators as well. Dual-energy X-ray absorptiometry (DXA) was utilized to evaluate the indicator of BMD. Serum irisin, BTMs, and BMD were compared between diabetic patients and healthy individuals. Pearson and Spearman correlation analyses were applied as well to assess correlations between irisin and BTMs and BMD. Multiple stepwise regression analysis was conducted to identify the independent factors of irisin. ROC curve analyses were carried out for serum irisin prediction for osteoporosis/osteopenia (OP). Results. The serum levels of irisin, procollagen type 1, intact N-terminal propeptide (P1NP), and osteocalcin (OC) were evidently lower in T2DM subjects than in NGT subjects (10.90 ± 1.88 vs .11.69 ± 2.06 ng/mL, < 0.05; 36.42(25.68,51.70) vs. 44.52(35.73,58.05)ng/ml, < 0.05; 16.15(12.40,21.66) vs. 18.70(15.56, 23.22)ng/ml, < 0.05). Among patients with T2DM, the circulating irisin level of those with OP was lower than that of normal BMD (9.98 ± 2.09 vs. 11.39 ± 1.57 ng/ml, < 0.01); irisin had a negative correlation with β-C-terminal telopeptides of type I collagen (β-CTX) (r = −0.496, < 0.001) and came back unrelated to Lumbar BMD; Lumbar BMD was negatively relevant to OC (r = −0.274, < 0.05) and β-CTX (r = −0.410, < 0.01). Multiple linear regression analyses of stepwise models implied that TG, LDL-C, and β-CTX were independently associated with serum irisin concentrations ( < 0.01 or < 0.05). Conclusion. Serum irisin level was declined in patients with type 2 diabetes diagnosed in the near term and had a certain association with bone turnover markers. It is suggested to consider irisin as a potential biomarker of bone metabolic disorder in T2DM patients with the initial diagnosis.

Activation of the NACHT leucine rich repeat and pyd domains‑containing 3 (NLRP3) inflammasome plays an important role in the initiation of inflammation in adipose tissue in diabetic patients. However, the mechanisms underlying this are not fully understood. Hydrogen sulfide (H2S) has been shown to have anti‑inflammatory properties in various cell types. The present study aimed to investigate the effect of H2S on high glucose (HG)‑induced NLRP3 inflammasome activation in adipocytes. Adipocytes were differentiated from 3T3‑L1 cells and treated with low glucose (LG), HG, H2S donor sodium hydrosulfide (NaHS) or N‑acetyl‑tyrosyl‑valyl‑​alanyl‑aspartyl chloromethyl ketone, an inhibitor of the cysteine protease caspase‑1. The expression levels of NLRP3, apoptosis‑associated speck‑like protein containing A CARD (ASC) and caspase‑1, and the release of interleukin (IL)‑1β and IL‑18 were measured. The results of the present study indicated that HG increased the expression levels of NLRP3, ASC and cleaved caspase‑1, and the release of IL‑1β and IL‑18 in adipocytes. Caspase‑1 inhibition abolished HG‑induced production of IL‑1β and IL‑18 in adipocytes. Furthermore, NaHS inhibited the expression of NLRP3, ASC and cleaved caspase‑1, and the production of IL‑1β and IL‑18 in adipocytes treated with HG. In conclusion, HG may increase and exogenous H2S may inhibit HG‑induced NLRP3 inflammasome activation in adipocytes.

Hydrogen sulfide (H₂S) has recently been identified as an endogenous gaseous signaling molecule. The aim of the present study was to investigate the effect of H₂S on high glucose- (HG-) induced ADAM17 expression and sFlt-1 production in 3T3-L1 adipocytes. Firstly, we found that HG DMEM upregulated the expression of ADAM17 and production of sFlt-1 in 3T3-L1 adipocytes. Knocking down ADAM17 attenuated the effect of high glucose on sFlt-1 production in adipocytes. HG decreased the expression of CSE and 3-MST, as well as the endogenous H₂S production. Furthermore, knocking down CSE and 3-MST significantly increased ADAM17 expression and sFlt-1 production. The addition of exogenous H₂S through the administration of sodium hydrosulfide (NaHS) inhibited HG-induced upregulation of ADAM17 expression and sFlt-1 production. In conclusion, decreased expression of CSE and 3-MST and the subsequent decrease in H₂S production contribute to high glucose-induced sFlt-1 production via activating ADAM17 in adipocytes. Exogenous H₂S donor NaHS has a potential therapeutic value for diabetic vascular complications.

Objective: To investigate the efficacy and safety of rituximab (RTX) as first-line treatment of acquired thrombotic thrombocytopenic purpura (aTTP). Methods: Twenty-five patients with acute aTTP and/or severe a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency were admitted to our centre from April 2009 to March 2015. Fourteen patients received RTX plus standard therapy (plasma exchange and corticosteroids) at acute episodes. Haemoglobin, platelet count, schistocytes, lactate dehydrogenase levels, ADAMTS13 activity and its inhibitors, and the ratio of B lymphocytes in the peripheral blood, were monitored. The number of plasma exchange (PEXs), total plasma volume, remission time, relapse ratio, and adverse effects were recorded. Results: The median number of PEXs was 5 (2–17) sessions and median total plasma volume was 168.43 ml/kg (62.86–469.52 ml/kg). Patients achieved haematological remission at a median of 15 days (5–22 days), and the median time of immunological remission was 2 weeks (2–8 weeks) with a median follow-up of 13 months (3–61 months). ADAMTS13 activity significantly increased after 2 weeks. The B lymphocyte percentage in peripheral blood was reduced 1 week after the first dose of RTX infusion compared with before treatment (2.21% ± 5.23% vs 18.47% ± 7.34%, P = 0.000 [the result of statistical software]), and began to gradually increase 9 months later. Severe adverse effects and relapsing TTP were not observed during therapy and follow-up. However, one patient who had sustained immunological remission died of severe pneumonia 7 months later. Conclusion: Although our study was limited by its small sample number and it was a non-controlled, clinical trial, it showed potential benefits of RTX therapy for acute aTTP. RTX may be administered as a first-line therapy for lowering patients’ relapse rate in the long term. Randomized, controlled trials of RTX for aTTP are required.