Centella triterpenes cream as a potential drug for the treatment of hypertrophic scar through inhibiting the phosphorylation of STAT3: A network pharmacology analysis and in vitro experiments.

BACKGROUND: Hypertrophic scars (HS) often affect the normal function and appearance of the skin and bring adverse effects to the body and mind of patients, being a challenge in the fields of burns and plastic surgery as well as rehabilitation. Despite significant efficacy of centella triterpenes cream for treating HS clinically, its pharmacodynamics and molecular targets are still unclear. Therefore, the network pharmacology analysis combined with in vitro cell molecular biology experiments was used to explore the mechanism and targets of centella triterpenes cream treating HS in this study. METHODS: First, target genes of asiaticoside (AC) were obtained from the databases including the Comparative Toxicogenomics Database, similarity ensemble approach, SwissTargetPrediction and TargetNet, and HS targets were acquired from the databases like Disgenet, GeneCards, and Online Mendelian Inheritance in Man. The common targets of AC-HS were obtained through plotting a Venn diagram. Subsequently, STRING 11.0 was employed for analyzing the protein-protein interaction (PPI) network of the common targets, and cytoscape 3.9.0 for analyzing the connectivity of PPI and plotting the network diagram of "drug-component-target". Additionally, a modified tissue culture method was applied to separate primary normal fibroblasts (NFs) in human skin and hypertrophic scar fibroblasts (HSFs). HSFs after 24-h AC treatment were subjected to MTT assay to detect cell viability, scratch assay to assess cell migration ability, and western blot to test the protein expression levels of STAT3, p-STAT3, transforming growth factor-ß1 (TGF-ß1), collagen I (COL 1), fibronectin 1 (FN1), and alpha-smooth muscle actin (α-SMA). RESULTS: In network pharmacology analysis, 134 pharmacodynamic targets of AC and 2333 HS targets were obtained after retrieving the database, 50 AC-HS common targets were obtained by a Venn diagram, and a total of 178 edges and 13 core genes such as JUN and STAT3 were acquired by PPI analysis. In vitro experiments showed that the phosphorylation level of STAT3 (p-STAT3) was increased in HSFs. In addition to reducing p-STAT3 in HSFs, AC significantly inhibited the cell viability and migration of HSFs and downregulated the protein levels of TGF-ß1, COL 1, FN 1, and α-SMA. CONCLUSION: STAT3 can be activated in HS. AC may exert its pharmacological effects of inhibiting TGF-ß1 signal transduction and regulating extracellular matrix remodeling in HS by inhibiting STAT3 phosphorylation. However, the specific molecular mechanism of AC remains to be verified through further experiments.

Multifunctional chitin-based barrier membrane with antibacterial and osteogenic activities for the treatment of periodontal disease.

The guided tissue regeneration technique is an effective approach to repair periodontal defect. However, collagen barrier membranes used clinically lose stability easily, leading to soft tissue invasion, surgical site infection, and failure of osteogenesis. An ideal barrier membrane should possess proper antibacterial, osteoconductive activities, and favorable biodegradation. In this study, zinc oxide nanoparticles were homogeneously incorporated into the chitin hydrogel (ChT-1%ZnO) through one-step dissolution and regeneration method from alkaline/urea solution the first time. The remaining weights of ChT-1%ZnO in 150 µg/mL lysozyme solution was 52% after 5 weeks soaking. ChT-1%ZnO showed statistical antibacterial activities for P. gingivalis and S. aureus at 6 h, 12 h, and 24 h. Moreover, ChT-1%ZnO exhibits osteogenesis promotion in vitro, and it was further evaluated with rat periodontal defect model in vivo. The cemento-enamel junction value in ChT-1%ZnO group is 1.608 mm, presenting a statistical difference compared with no-membrane (1.825 mm) and ChT group (1.685 mm) after 8 weeks postoperatively.

How to Break a Fever: A Feedback Circuit for Body Temperature Control.

Body temperature control is a critical brain function. In this issue of Neuron, Wang et al. identify a negative feedback circuit in mouse preoptic area of the hypothalamus that regulates body temperature to counter fever.

Effects of selenium on the antioxidant enzymes response of Neocaridina heteropoda exposed to ambient nitrite.

The effects of dietary Selenium (Se) supplementation on muscle superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) activities and haemolymph superoxide anions (O(2)-) of Neocaridina heteropoda exposed to ambient nitrite were investigated. The results showed supplementation of Se in diet could enhance the resistance of shrimp to low concentration ambient nitrite. The results demonstrated that Se might have a potentially useful role as an effective antioxidant and resistance to aqueous nitrite in shrimp and the effect of the organic Se was better than that of the inorganic Se.