Effects of Intensive Glycemic Control on Serum Exosome miR-126-3p and miR-125b-1-3p Levels and Wound Healing in Patients with Diabetic Ulcers.

Objective: Intensive glycemic control and exosomal miRNAs have both been reported to improve wound repair in diabetic ulcers. In this study, we aimed to investigate the effects of intensive glycemic control on serum exosome microRNA-126-3p (miR-126-3p), microRNA-125b-1-3p (miR-125b-1-3p), and wound healing in patients with diabetic ulcers. Methods: Herein, 45 diabetic patients with an ulcer, aged 35-75 years old, were randomly assigned to the intensive glycemic control group (n = 21) and the conventional glycemic control group (n = 24). Serum exosomes were extracted in the laboratory and assessed by Western blotting, transmission electron microscopy, and nanoparticle tracking analysis. The expression of miR-126-3p and miR-125b-1-3p was validated using quantitative real-time polymerase chain reaction. The wound healing of each diabetic ulcer patient was measured and imaged; additionally, clinical and follow-up data were collected. Finally, the clinical and laboratory data were combined for statistical analysis. Results: Intensive glycemic control was significantly more conducive to wound healing and infection control than conventional glycemic control (P < 0.05). Serum exosomal miR-126-3p was negatively correlated with fasting plasma glucose levels (r = 0.34, P < 0.05) and positively associated with the wound healing rate (r = 0.45, P < 0.01). The level of miR-126-3p in the intensive glycemic control group was significantly higher than that in the conventional glycemic control group (P < 0.01). Serum exosomal miR-125b-1-3p was not correlated with blood glucose levels (r = 0.03, P > 0.05) and was positively associated with the wound healing rate (r = 0.33, P < 0.05). No significant difference was observed in the level of miR-125b-1-3p between the intensive and conventional glycemic control groups. Regarding the prognosis of diabetic ulcers, the intensive glycemic control group was better than the conventional group (Z = -2.02, P < 0.05). Conclusion: Serum exosome (miR-125b-1-3p and miR-126-3p) levels are correlated with wound healing in diabetic ulcers. Intensive glycemic control increases the serum exosomal miR-126-3p level, which might be one of the mechanisms that promotes wound healing in diabetic ulcers.

Qingyihuaji Formula promotes apoptosis and autophagy through inhibition of MAPK/ERK and PI3K/Akt/mTOR signaling pathway on pancreatic cancer in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingyihuaji Formula (QYHJ), a widely used traditional Chinese medicine (TCM), has been used to treat patients with cancer in China. However, the effect and mechanism of QYHJ on pancreatic ductal adenocarcinoma (PDAC) remains unclear. AIM OF THE STUDY: This study aimed to explore the roles and evaluate the possible underlying molecular mechanisms of QYHJ and its core component in PDAC using label-free quantitative proteomics in conjunction with network pharmacology-based analysis. MATERIALS AND METHODS: By screening differentially expressed proteins (DEPs) in proteomics and QYHJ-predicted gene sets, we identified QYHJ-related PDAC targets annotated with bioinformatic analysis. A subcutaneous tumor model was established to assess the role of QYHJ in vivo. The effects of quercetin (Que), a core component of QYHJ, on cell proliferation, migration, invasion, apoptosis, and autophagy in SW1990 and PANC-1 cells were investigated in vitro. Immunohistochemistry, western blotting, mRFP-GFP-LC3 adenovirus, and kinase analysis were used to determine the underlying mechanisms. RESULTS: Bioinformatics analysis revealed that 41 QYHJ-related PDAC targets were closely related to the cellular response to nitrogen compounds, positive regulation of cell death, regulation of epithelial cell apoptotic processes, and chemokine signaling pathways. CASP3, SRC, STAT1, PTPN11, PKM, and PAK1 with high expression were identified as hub DEPs in the PPI network, and these DEPs were associated with poor overall survival and STAT 1, MAPK/ERK, and PI3K/Akt/mTOR signaling pathways in PDAC patients. QYHJ significantly promoted tumor death in nude mice. Moreover, quercetin inhibited the proliferation, migration, and invasion of PDAC cells. Additionally, Que induced apoptosis and autophagy in PDAC cells. Mechanistically, QYHJ and Que significantly activated STAT 1 and remarkably inhibited the MAPK/ERK and PI3K/Akt/mTOR signaling pathways in vivo and in vitro, respectively. Importantly, ERK1/2 inactivation contributes to que-induced apoptosis in SW1990 and PANC-1 cells. CONCLUSIONS: These results suggest that QYHJ and Que are promising anti-PDAC avenues that benefit from their multiform mechanisms.

Effects of Moist Exposed Burn Therapy and Ointment (MEBT/MEBO) on the autophagy mTOR signalling pathway in diabetic ulcer wounds.

Context: Burn therapy (MEBT)/moist exposed burn ointment (MEBO) is an effective traditional Chinese medicine method to treat diabetic wound, but the mechanism is unclear. Autophagy has been proved to be closely related with wound healing, so MEBO/MEBT is hypothesized to promote diabetic wound healing by regulating autophagy.Objective: To explore the mechanism of moist exposed MEBT/MEBO promoting diabetic wound repair.Materials and methods: Eighty male Wistar rats were randomly assigned to control (n = 20) and diabetic group induced by intraperitoneal injection of STZ (n = 60), which were further randomly assigned to MEBO, Kangfuxin and model groups (n = 20 each). All rats underwent full-thickness skin resection in the back. Wound healing was dynamically observed and wound tissues were collected at five time points for pathological examination, autophagosome and the expression of PI3K, Akt and mTOR.Results: The healing time in the control group was the shortest, no statistically significant difference was found between the MEBO and the Kangfuxin group (p = 0.76). The morphology of autophagosomes ranged large to small, which was the most obvious in the MEBO group. The mRNA and protein expression of PI3K, Akt and mTOR in each group reached the peak on Day 5, the levels in the MEBO group were the highest (F = 18.43, 19.97, 15.36, p < 0.05). On Day 11, the expression levels in each group began to decline.Discussion and conclusions: In this study, we discussed the molecular mechanism of MEBT/MEBO promoting the repair of diabetic ulcer wounds through autophagy and PI3K-Akt-mTOR signalling pathway, which provides a new way for drug design in the future.

Anti-inflammatory triterpenes from the leaves of Rosa laevigata.

Bioassay-guided fractionation of an EtOAc extract of the leaves of Rosa laevigata afforded two new 19-oxo-18,19-seco-ursane-type triterpenes (1 and 3), a new ursane-type nortriterpene (2), a new ursane-type triterpene lactone saponin (4), and two new oleanane-type triterpenoids (5 and 6), together with eight known triterpenoids (7-14). Compound 1, a 19-oxo-18,19-seco-28-norursane, possesses a conjugated diene between C-12 and C-17. Several of the isolated compounds (1, 5, 7, 11, and 13) exhibited moderate activities in anti-inflammatory assays in vitro.