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Page 3 of 29A c c e p t e d M a n u s c r i p t ABSTRACT Objective: Periodontium regeneration is one of the most important processes for periodontitis therapy. Human periodontal ligament cells (hPDLCs) play a vital role in the repair and regeneration of periodontal tissues. Our study aimed to investigated the mechanisms underlying the promotion of hPLDCsosteogenic differentiation by baicalein. Design: hPDLCs were obtained from periodontal ligament (PDL) tissues by primary culture. The MTT assay was used to determine the growth curves of hPDLCs treated with different concentrations of baicalein (1.25, 2.5, 5, or 10 μM). Alkaline phosphatase (ALP) staining and Alizarin red S staining were performed to assess osteogenic differentiation of hPDLCs administered baicalein. Osteogenic differentiation-related gene and protein expression levels and Wnt/β-catenin pathway signal changes were assessed by qRT-PCR and Western blotting analysis.
Results:The results showed that baicalein decreased the growth of hPDLCs slightly and increased ALP activity and calcium deposition in a dose-dependent manner. The expression of runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2), Osterix (OSX) and osteocalcin (OCN) were elevated after baicalein administration. Moreover, baicalein strongly activated the Wnt/β-catenin pathway and up-regulated the expression of β-catenin, lymphoid enhancer factor 1 (LEF1) and Cyclin D1. Dickkopf-related protein 1 (DKK-1) significantly reversed the effects of baicalein on hPDLCs. Conclusions: Our findings indicated that baicalein enhanced the osteogenic differentiation of hPDLCs via the activation of the Wnt/β-catenin signaling pathway, which may represent a potential candidate for periodontitis therapy.
These results indicate that nicotine prevents the increased osteogenic potential of hPDLCs induced by cyclic tensile stress by binding to an α7 nicotinic acetylcholine receptor and activating the canonical Wnt pathway.
Mechanical strain plays an important role in bone formation and resorption during orthodontic tooth movement. The mechanism has not been fully studied, and the process becomes complex with increased amounts of periodontal patients seeking orthodontic care. Our aims were to elucidate the combined effects of proinflammatory cytokines and intermittent cyclic strain (ICS) on the osteogenic capacity of human periodontal ligament cells. Cultured human periodontal ligament cells were exposed to proinflammatory cytokines (interleukin-1β 5 ng/mL and tumor necrosis factor-α 10 ng/mL) for 1 and 5 days, and ICS (0.5 Hz, 12% elongation) was applied for 4 h per day. The autocrine of inflammatory cytokines was measured by enzyme-linked immunosorbent assay. The expression of osteoblast markers runt-related transcription factor 2 and rabbit collagen type I was determined using real-time polymerase chain reaction and Western blot. The osteogenic capacity was also detected by alkaline phosphatase (ALP) staining, ALP activity, and alizarin red staining. We demonstrated that ICS impaired the osteogenic capacity of human periodontal ligament cells when incubated with proinflammatory cytokines, as evidenced by the low expression of ALP staining, low ALP activity, reduced alizarin red staining, and reduced osteoblast markers. These data, for the first time, suggest that ICS has a negative effect on the inductive inhibition of osteogenicity in human PDL cells mediated by proinflammatory cytokines.
It is well known that arginase II leads to decreased synthesis of nitric oxide (NO) by competing with endothelial nitric oxide synthase (eNOS) for their same substrate L-arginine. However, the regulatory mechanisms of arginase II production remain unclear. In this study, we hypothesized that poly- (ADP-ribose) transferase/polymerase-1 (PARP-1) may be a critical factor responsible for ox-LDL (oxidized Low Density Lipoprotein)-enhanced arginase II activity. We used serial deletions within plasmid constructs and found that a core promoter region of arginase II was located at the element of -774 to -738 bp and PARP-1 was identified specifically binding to this region. Inhibition of PARP-1 markedly reduced the endogenous arginase II expression and enhanced eNOS and NO production. Similarly, ox-LDL-induced increase in arginase II production and eNOS and NO reduction was substantially abolished by PARP-1 inhibition both in vitro and in vivo. Significant decrease in arginase II expression and increase in eNOS expression and NO levels, as well as improved endothelial function were observed in PARP-1-/- mice. The underlying mechanisms of ox-LDL-induced changes of PARP-1 expression involved migration of phosphorylated ERK2 into nuclei and direct interaction with PARP-1 which dramatically enhanced PARP-1 production, followed by histone acetylation to activate arginase II transcription process. Our studies demonstrated for the first time that PARP-1 regulates basal transcription process and ox-LDL-induced up-regulation of arginase II. These results demonstrated that PARP-1 offers a promising therapeutic target for endothelial dysfunction and atherosclerosis.
Background:
In laparoscopic right hemicolectomy for right colon cancer, complete mesocolic excision is a standard procedure that involves extended lymphadenectomy and blood vessel ligation. This study aimed to establish a nomogram to facilitate evaluation of the surgical difficulty of laparoscopic right hemicolectomy based on preoperative parameters.
Materials and methods:
The preoperative clinical and computed tomography-related parameters, operative details, and postoperative outcomes were analyzed. The difficulty of laparoscopic colectomy was defined using the scoring grade reported by Escal et al. with modifications. Multivariable logistic analysis was performed to identify parameters that increased the surgical difficulty. A preoperative nomogram to predict the surgical difficulty was established and validated.
Results:
A total of 418 consecutive patients with right colon cancer who underwent laparoscopic radical resection at a single tertiary medical center between January 2016 and May 2022 were retrospectively enrolled. The patients were randomly assigned to a training data set (n=300, 71.8%) and an internal validation data set (n=118, 28.2%). Meanwhile, an external validation data set with 150 consecutive eligible patients from another tertiary medical center was collected. In the training data set, 222 patients (74.0%) comprised the non-difficulty group and 78 (26.0%) comprised the difficulty group. Multivariable analysis demonstrated that adipose thickness at the ileocolic vessel drainage area, adipose area at the ileocolic vessel drainage area, adipose density at the ileocolic vessel drainage area, presence of the right colonic artery, presence of type III Henle’s trunk, intra-abdominal adipose area, plasma triglyceride concentration, and tumor diameter at least 5 cm were independent risk factors for surgical difficulty; these factors were included in the nomogram. The nomogram incorporating seven independent predictors showed a high C-index of 0.922 and considerable reliability, accuracy, and net clinical benefit.
Conclusions:
The study established and validated a reliable nomogram for predicting the surgical difficulty of laparoscopic colectomy for right colon cancer. The nomogram may assist surgeons in preoperatively evaluating risk and selecting appropriate patients.
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