Apical papilla stem cell-derived exosomes regulate lipid metabolism and alleviate inflammation in the MCD-induced mouse NASH model.

Stem cells from the apical papilla(SCAPs) exhibit remarkable tissue repair capabilities, demonstrate anti-inflammatory and pro-angiogenic effects, positioning them as promising assets in the realm of regenerative medicine. Recently, the focus has shifted towards exosomes derived from stem cells, perceived as safer alternatives while retaining comparable physiological functions. This study delves into the therapeutic implications of exosomes derived from SCAPs in the methionine-choline-deficient (MCD) diet-induced mice non-alcoholic steatohepatitis (NASH) model. We extracted exosomes from SCAPs. During the last two weeks of the MCD diet, mice were intravenously administered SCAPs-derived exosomes at two distinct concentrations (50 µg/mouse and 100 µg/mouse) biweekly. Thorough examinations of physiological and biochemical indicators were performed to meticulously evaluate the impact of exosomes derived from SCAPs on the advancement of NASH in mice induced by MCD diet. This findings revealed significant reductions in body weight loss and liver damage induced by the MCD diet following exosomes treatment. Moreover, hepatic fat accumulation was notably alleviated. Mechanistically, the treatment with exosomes led to an upregulation of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) levels in the liver, enhancing hepatic fatty acid oxidation and transporter gene expression while inhibiting genes associated with fatty acid synthesis. Additionally, exosomes treatment increased the transcription levels of key liver mitochondrial marker proteins and the essential mitochondrial biogenesis factor. Furthermore, the levels of serum inflammatory factors and hepatic tissue inflammatory factor mRNA expression were significantly reduced, likely due to the anti-inflammatory phenotype induced by exosomes in macrophages. The above conclusion suggests that SCAPs-exosomes can improve NASH.

Diabetic and nondiabetic BMSC-derived exosomes affect bone regeneration via regulating miR-17-5p/SMAD7 axis.

Diabetic bone disease (DBD) is a complication of diabetes mellitus (DM) and is characterized by impaired osteocyte function and delayed bone remodeling due to high blood glucose levels and sustained release of inflammatory factors. Recent studies show that the regulation of osteoblasts (OBs) by bone marrow stromal cells (BMSCs) is an important mechanism in alleviating DBD and that exosomes are recognized as the key medium. Mesenchymal stem cell-derived exosome (MSC-Exos) therapy is a promising approach to facilitate tissue repair. However, the influence of exosomes from diabetic conditioned BMSCs on OBs and bone regeneration, as well as the underlying mechanism, are still elusive. Here, we used high-glucose medium to mimic diabetic conditions and normal-glucose medium as control to mimic nondiabetic conditions in vitro and found that microRNA-17 (miR-17) was downregulated in diabetic-conditioned BMSC-derived exosomes (HG-Exos), HG-Exo-co-cultured osteoblasts, and the skull of rats with type 2 diabetes mellitus (T2DM). Further experiment concluded that nondiabetic conditioned BMSC-Exos (NG-Exos) promoted the osteogenesis of OBs and bone regeneration of rats with T2DM via upregulation of miR-17. Compare with NG-Exos, HG-Exos impeded osteogenesis of OBs in vitro and bone regeneration of rats in vivo by downregulation of miR-17. Moreover, miR-17 promoted bone regeneration by targeting SMAD7, which was further proved to have a negative effect on osteogenesis. Taken together, nondiabetic BMSC-derived exosomes greatly foster bone regeneration, whereas diabetic BMSC-derived exosomes undermine the promotion effect of MSC-Exos by regulating the miR-17/SMAD7 axis. These findings provide support for the miR-17-5p/SMAD7 axis as a promising therapeutic target to treat DBD.

Rapid detection of human heart-type fatty acid-binding protein in human plasma and blood using a colloidal gold-based lateral flow immunoassay.

The incidence of acute myocardial infarction (AMI) is currently increasing. Early detection is important for the treatment and prognosis of patients with AMI. Heart-type fatty acid-binding protein (H-FABP) may be used as an early marker of AMI due to its high sensitivity, specificity and prognostic value. Therefore, in the present study, H-FABP was used as a biomarker in a double-antibody sandwich method and colloidal gold-based lateral flow immunoassay to develop a rapid detection kit for H-FABP with a processing time of only 5 min. The sensitivity of the kit in plasma and whole blood was 1 ng/ml and this method had good specificity, exhibiting no cross-reaction with cardiac troponin I, myoglobin or creatine kinase-Mb. The kits had good shelf life and stability, as they were able to be stored at 40˚C for 30 days. A total of 12 clinical samples were collected for detection and the coincidence rate with the ELISA method was up to 91.67%. Therefore, the present study provided a simple, rapid and economical early-detection in-home testing kit.

Intrinsically flame-retardant polyamide 66 with high flame retardancy and mechanical properties.

The key factor in the synthesis of intrinsic flame retardant polymers is the thermal stability and reactivity of phosphorus-based flame retardants. However, it is difficult to realize both thermal stability and high reactivity by using one phosphorus-based flame retardant. Herein, we proposed a strategy to improve the thermal stability of highly reactive flame-retardant, 4-(2-(((2-carboxyethyl)(phenyl)phosphoryl)oxy)ethoxy)-4-oxohexanoic acid (CPPOA), by reacting it with 1,6-diaminohexane to obtain CPPOA salt, which then was copolymerized with PA66 salt to obtain intrinsic flame-retardant polyamide 66 (FRPA66). The thermal stability of CPPOA was significantly improved. The LOI and vertical combustion grade of FRPA66 with 6 wt% CPPOA reached 27.2% and V-0 rating, respectively. Furthermore, the tensile strength and impact strength of the FRPA66 reached 70 MPa and 5.6 kJ m-2, respectively. Our work presents an efficient approach to synthesize polymers having high flame retardancy and good mechanical properties, showing high potential for real applications.