Abstract Inducing of dental pulp stem cells (DPSCs) into endothelial cells (ECs) to prevascularize pulp tissue constructs may offer a novel and viable approach for enhancing pulp regeneration. However, there are numerous challenges in current methods for the acquisition of sufficient translational ECs. It was known that Sema4D/PlexinB1 signaling exerts profound effects on enhancing vascular endothelial growth factor (VEGF) secretion and angiogenesis. Whether Sema4D/PlexinB1 could regulate endothelial differentiation of DPSCs is not yet investigated. In this study, when DPSCs were treated with Sema4D (2 μg/mL), ECs‐specific (VEGFR1, VEGFR2, CD31, and vWF), and angiogenic genes and proteins were significantly upregulated. The induced ECs exhibited similar endothelial vessel formation ability to that of human umbilical vein endothelial cells (HUVECs). Furthermore, phosphorylation of AKT increased dramatically within 5 minutes (from 0.93 to 21.8), while p ‐ERK1/2 was moderately elevated (from 0.94 to 2.65). In summary, our results demonstrated that Sema4D/PlexinB1 signaling induces endothelial differentiation of DPSCs. The interactions of Sema4D, VEGF, ANGPTL4, ANG1, and HIF‐1α may play a crucial role in mediating the differentiation process.
This study aimed to evaluate the role of Semen Brassicae, a common Traditional Chinese Medicine, in the treatment of hypertension.Spontaneously hypertensive rats (SHRs) were divided into five groups and were gavaged with either distilled water, water-decocted solution from Semen Brassicae (0.5, 1 or 2 g/kg), or nifedipine (2.7 mg/kg). Normal rats gavaged with distilled water were used as a control. Systolic (SBP) and diastolic blood pressure (DBP) were measured using a non-invasive method. After 8 weeks of administration, all animals were anesthetized. Abdominal aortic serum was collected to measure serum factors; the thoracic aorta was collected for hematoxylin and eosin staining and western blot analysis.Both SBP and DBP were significantly decreased after Semen Brassicae treatment. Endothelin-1 and angiotensin II levels in abdominal aortic serum, as well as the levels of inflammatory factors interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha, were significantly decreased after Semen Brassicae treatment. The wall thickness of the thoracic aorta was significantly reduced after Semen Brassicae treatment. Nitric oxide level and the activity of superoxide dismutase and glutathione peroxidase were significantly increased, and malondialdehyde level was significantly decreased in the abdominal aortic serum after Semen Brassicae treatment. Semen Brassicae treatment increased the levels of peroxisome proliferator-activated receptor gamma and IκB-α and decreased the levels of intercellular adhesion molecule 1, monocyte chemoattractant protein-1, von Willebrand factor, p-IκB-α and p-p65 NF-κB.In conclusion, water-decocted solution from Semen Brassicae can decrease blood pressure, improve vascular remodeling, and attenuate oxidative stress and inflammation in SHRs.
Chlorhexidine (CHX) is widely considered to be the gold standard for preventing dental caries. However, it is possible to induce resistance to CHX. The LiaSR two-component system has been identified that contributed to CHX resistance in Streptococcus mutans, which is one of the major pathogens in dental caries. However, the underlying mechanisms remain unclear. In this study, an MIC assay and a viability assessment demonstrated that after deleting the liaS and liaR genes, the sensitivity of mutants could increase. The Nile Red efflux assay exhibited that the efflux rates of mutants were significantly decreased. The RT-qPCR results indicated that the LiaSR two-component system-mediating influence on the expression of lmrB in S. mutans contributed to the efflux rate. The hydrophobicity assay and membrane potential assay showed that the mutants had higher levels of hydrophobicity and depolarization, suggesting that their membranes were more easily disturbed. The TEM graphs revealed that the border of the cell membrane was unclear in mutants compared with the wild-type strain, indicating that the cell envelope’s stress response may have been inhibited. While the surface charge of mutants showed no significant difference in the wild-type strain according to the result of cytochrome c-based charged determination. This study provides valuable novel insights into the mechanisms of the LiaSR two-component system in the CHX resistance of S. mutans.
Angong Niuhuang pill, a Chinese materia medica preparation, can improve neurological functions after acute ischemic stroke. Because of its inconvenient application and toxic components (Cinnabaris and Realgar), we used transdermal enhancers to deliver Angong Niuhuang pill by modern technology, which expanded the safe dose range and clinical indications. In this study, Angong Niuhuang stickers administered at different point application doses (1.35, 2.7, and 5.4 g/kg) were administered to the Dazhui (DU14), Qihai (RN6) and Mingmen (DU4) of rats with chronic cerebral ischemia, for 4 weeks. The Morris water maze was used to determine the learning and memory ability of rats. Hematoxylin-eosin staining and Nissl staining were used to observe neuronal damage of the cortex and hippocampal CA1 region in rats with chronic cerebral ischemia. The middle- and high-dose point application of Angong Niuhuang stickers attenuated neuronal damage in the cortex and hippocampal CA1 region, and improved the memory of rats with chronic cerebral ischemia with an efficacy similar to interventions by electroacupuncture at Dazhui (DU14), Qihai (RN6) and Mingmen (DU4). Our experimental findings indicate that point application with Angong Niuhuang stickers can improve cognitive function after chronic cerebral ischemia in rats and is neuroprotective with an equivalent efficacy to acupuncture.
Objective To develop a rat model of periapical periodontitis caused by repeated root canal infection with Enterococcusfaecalis (E.faecalis),and to evaluate the disease progression by observing the periapical lesion area, inflammation,and TNF-αexpression in the root apex.Methods Thirty Sprague Dawley rats were used in this study.The pulps of the bilateral first maxillary molar teeth of each rat were exposed,absorbent cotton with lipopolysaccharides(LPS)was implanted,and then the teeth were exposed in the oral environment for four weeks to induce periapical periodontitis of primary root canal infection with mixed bacteria.Then the root canal was subjected to disinfection treatment for two weeks,followed by inoculation with E.faecalis suspension for one week to produce repeated root canal infection model with E.faecalis for a 3- week observation.X-ray,H-E staining and immunohistochemical staining were used to observe the periapical lesion area, inflammation,and TNF-αexpression in the root apex at one week,two weeks,three weeks after establishment of repeated root canal infection model;the above parameters were also observed for periapical periodontitis caused by primary root canal infection with mixed bacteria(6weeks later)and for root canal disinfected by Ca(OH)2(for 6weeks).Results (1)Periapical periodontitis caused by repeated root canal infection with E.faecalis had gradually increased periapical lesion area,with unclear damage border;the infection reached a severe level during the 1-2weeks and became chronic inflammation at week three;and the expression of TNF-αbegan to decrease after two weeks.(2)The periapical periodontitis caused by primary root canal infection with mixed bacteria had a smaller periapical lesion area,with clear damage border,slighter infiltration of inflammatory cells,and less TNF-αexpression.(3)The periapical periodontitis with root canal disinfected by Ca(OH)2had the smallest periapical lesion area,with disappeared inflammation,slight TNF-αexpression,and hyperplasia of cementum and alveolar bone.Conclusion E.faecalis has a strong periapical damaging effect,with continuous bone absorption observed even under the chronic inflammatory status.
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