Injectable Erythrocyte Gel Loaded with Bulleyaconitine A for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with clinical manifestations including joint cartilage, synovitis, and bone damage. Here we developed an injectable erythrocyte gel loaded with Bulleyaconitine A (BLA) for the treatment of RA and demonstrated its anti-inflammatory effects in vivo and in vitro. In vitro experiments showed that BLA could effectively down-regulate the expression of pro-inflammatory factor in activated macrophages through the nuclear factor-κB (NF-κB) pathway. In vivo experiments have shown that the injection of BLA@RBCs in the inflammatory joints of CIA mice increases the local concentration of BLA in a long time. Improved therapeutic outcomes and reduced toxicity of BLA are demonstrated in our work. Together, the developed BLA@RBCs drug delivery system provides an alternative strategy to treat RA joints and shows high potential in clinical RA treatment.

Injectable ROS-scavenging hydrogel with MSCs promoted the regeneration of damaged skeletal muscle.

Skeletal muscle injury is a common disease accompanied by inflammation, and its treatment still faces many challenges. The local inflammatory microenvironment can be modulated by a novel ROS-scavenging hydrogel (Gel) we constructed. And MSCs could differentiate into myoblasts and contribute to muscle tissue homeostasis and regeneration. Here, Gel loaded with mesenchymal stem cells (MSCs) (Gel@MSCs) was developed for repairing the injured skeletal muscle. Results showed that the Gel improved the survivability and enhanced the proliferation of MSCs (≈two-fold), and the Gel@MSCs inhibited the local inflammatory responses as it promoted polarization of M2 macrophages (increased from 5% to 17%), the mediator of the production of anti-inflammatory factors. Western blotting and qPCR revealed the Gel promoted the expression of proteins (≈two-fold) and genes (≈two to six-fold) related to myogenesis in MSCs. Histological assessment indicated that the Gel or MSCs promoted regeneration of skeletal muscle, and the efficacy was more significant at Gel@MSCs than MSCs alone. Finally, behavioral experiments confirmed that Gel@MSCs improved the motor function of injured mice. In short, the Gel@MSCs system we constructed presented a positive effect on reducing skeletal muscle damage and promoted skeletal muscle regeneration, which might be a novel treatment for such injuries.

The angiotensin-I converting enzyme gene I/D variation contributes to end-stage renal disease risk in Chinese patients with type 2 diabetes receiving hemodialysis.

Whether the DD genotype of the angiotensin-I converting enzyme (ACE) I/D variation contributes to end-stage renal disease (ESRD) risk in type 2 diabetes mellitus (T2DM) remains controversial. Differences in study design, case and control definition, sample size and ethnicity may contribute to the discrepancies reported in association studies. We performed a case-control study to evaluate the association of the ACE I/D variation with ESRD risk in Chinese patients with T2DM receiving hemodialysis and analyzed the genotype-phenotype interaction. Unrelated Chinese patients (n = 432) were classified into the non-diabetic nephropathy (DN) control group (n = 222, duration of diabetes >10 years, no signs of renal involvement) and the DN-ESRD group (n = 210; ESRD due to T2DM, receiving hemodialysis). Polymerase chain reaction was used to genotype ACE I/D for all 432 subjects. The frequencies of the ID + DD genotypes were higher in the DN-ESRD group than non-DN control group (65.2 vs. 50.9 %; adjusted OR 1.98 (95 % CI, 1.31-3.00; P = 0.001). In the DN-ESRD group, the DD genotypic subgroup had significantly elevated HbA1c and diastolic blood pressure (DBP) compared to the II subgroup (both P < 0.05). The DD genotype of the ACE I/D variation may be associated with more elevated blood pressure and HbA1c, and therefore may predict the development, progression and severity of DN-ESRD in Chinese patients with T2DM undergoing hemodialysis.