Circ_0004872 deficiency attenuates ox-LDL-induced vascular smooth muscle cell dysfunction by miR-424-5p-dependent regulation of FRS2.

Atherosclerosis (AS) is a pivotal pathological basis of cardiovascular and cerebrovascular diseases, and circular RNAs (circRNAs) has been disclosed to exert a vital part in the progression of AS. However, the functions of circ_0004872 in the progression of AS is indistinct. In this context, we aimed to elucidate the role of circ_0004872 and the potential mechanism in AS. The level of circ_0004872, miR-424-5p and fibroblast growth factor receptor substrate 2 (FRS2) was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was monitored by Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine (EDU) assays. The invasion and migration capabilities of VSMCs were tested by transwell assays and wound-healing assay, respectively. Western blot was adopted to check the protein levels of CyclinD1, Vimentin and FRS2. Dual-luciferase reporter and RNA immunoprecipitation assay were executed to manifest the interaction between miR-424-5p and circ_0004872 or FRS2. The level of circ_0004872 was increased in the serum samples of AS patients and ox-LDL-exposed VSMCs. Ox-LDL exposure triggered cell proliferation, invasion and migration ability of VSMCs. depletion of circ_0004872 partly weakened ox-LDL-mediated effects in VSMCs. Mechanistically, circ_0004872 functioned as a sponge of miR-424-5p, and miR-424-5p inhibition partly alleviated circ_0004872 deficiency-mediated influences in VSMCs. Additionally, miR-424-5p interacted with FRS2, and miR-424-5p constrained dysfunction in ox-LDL-stimulated VSMCs via reducing FRS2 level. Notably, circ_0004872 functioned as a sponge of miR-424-5p to elevate FRS2 expression. Circ_0004872 accelerated ox-LDL-induced damage via mediating miR-424-5p/FRS2 axis.

Triterpenoids from the Leaves of Diospyros digyna and Their PTP1B Inhibitory Activity.

Six new 2α-hydroxy ursane triterpenoids, 3α-cis-p-coumaroyloxy-2α,19α-dihydroxy-12-ursen-28-oic acid (1), 3α-trans-p-coumaroyloxy-2α,19α-dihydroxy-12-ursen-28-oic acid (2), 3α-trans-p-coumaroyloxy-2α-hydroxy-12-ursen-28-oic acid (3), 3ß-trans-p-coumaroyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (4), 3ß-trans-feruloyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (5), and 3α-trans-feruloyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (6), along with eleven known triterpenoids (7-17), were isolated from the leaves of Diospyros digyna. Their chemical structures were elucidated by comprehensive analysis of UV, IR, HRESIMS, and NMR spectra. All the isolated compounds were evaluated for their PTP1B inhibitory activity. 3ß-O-trans-feruloyl-2α-hydroxy-urs-12-en-28-oic acid (13) showed the best inhibition activity with an IC50 value of 10.32 ± 1.21 µM. The molecular docking study found that the binding affinity of compound 13 for PTP1B was comparable to that of oleanolic acid (positive control).

PSO/SDF-1 composite hydrogel promotes osteogenic differentiation of PDLSCs and bone regeneration in periodontitis rats.

Periodontitis is an inflammatory disease characterized by the destruction of periodontal tissues, and the promotion of bone tissue regeneration is the key to curing periodontitis. Psoralen is the main component of Psoralea corylifolia Linn, and has multiple biological effects, including anti-osteoporosis and osteogenesis. We constructed a novel hydrogel loaded with psoralen (PSO) and stromal cell-derived factor-1 (SDF-1) for direct endogenous cell homing. This study aimed to evaluate the synergistic effects of PSO/SDF-1 on periodontal bone regeneration in patients with periodontitis. The results of CCK8, alkaline phosphatase (ALP) activity assay, and Alizarin Red staining showed that PSO/SDF-1 combination treatment promoted cell proliferation, chemotaxis ability, and ALP activity of PDLSCs. qRT-PCR and western blotting showed that the expression levels of alkaline phosphatase (ALP), dwarf-associated transcription factor 2 (RUNX2), and osteocalcin (OCN) gene were upregulated. Rat periodontal models were established to observe the effect of local application of the composite hydrogel on bone regeneration. These results proved that the PSO/SDF-1 combination treatment significantly promoted new bone formation. The immunohistochemical (IHC) results confirmed the elevated expression of ALP, RUNX2, and OCN osteogenic genes. PSO/SDF-1 composite hydrogel can synergistically regulate the biological function and promote periodontal bone formation. Thus, this study provides a novel strategy for periodontal bone regeneration.

The mechanism of low molecular weight fucoidan-incorporated nanofiber scaffolds inhibiting oral leukoplakia via SR-A/Wnt signal axis.

Oral leukoplakia (OLK) is the most common oral precancerous lesion, and 3%-17% of OLK patients progress to oral squamous cell carcinoma. OLK is susceptible to recurrence and has no effective treatment. However, conventional drugs have significant side effects and limitations. Therefore, it is important to identify drugs that target OLK. In this study, scavenger receptor A (SR-A) was found to be abnormally highly expressed in the oral mucosal epithelial cells of OLK patients, whereas molecular biology studies revealed that low molecular weight fucoidan (LMWF) promoted apoptosis of dysplastic oral keratinocytes (DOK) and inhibited the growth and migration of DOK, and the inhibitory effect of LMWF on OLK was achieved by regulating the SR-A/Wnt signaling axis and related genes. Based on the above results and the special situation of the oral environment, we constructed LMWF/poly(caprolactone-co-lactide) nanofiber membranes with different structures for the in-situ treatment of OLK using electrospinning technology. The results showed that the nanofiber membranes with a shell-core structure had the best physicochemical properties, biocompatibility, and therapeutic effect, which optimized the LMWF drug delivery and ensured the effective concentration of the drug at the target point, thus achieving precise treatment of local lesions in the oral cavity. This has potential application value in inhibiting the development of OLK.