Nocardamine mitigates cellular dysfunction induced by oxidative stress in periodontal ligament stem cells.

BACKGROUND: The role of periodontal ligament stem cells (PDLSCs) in repairing periodontal destruction is crucial, but their functions can be impaired by excessive oxidative stress (OS). Nocardamine (NOCA), a cyclic siderophore, has been shown to possess anti-cancer and anti-bacterial properties. This study aimed to investigate the protective mechanisms of NOCA against OS-induced cellular dysfunction in PDLSCs. METHODS: The cytotoxicity of NOCA on PDLSCs was assessed using a CCK-8 assay. PDLSCs were then treated with hydrogen peroxide (H2O2) to induce OS. ROS levels, cell viability, and antioxidant factor expression were analyzed using relevant kits after treatment. Small molecule inhibitors U0126 and XAV-939 were employed to block ERK signaling and Wnt pathways respectively. Osteogenic differentiation was assessed using alkaline phosphatase (ALP) activity staining and Alizarin Red S (ARS) staining of mineralized nodules. Expression levels of osteogenic gene markers and ERK pathway were determined via real-time quantitative polymerase chain reaction (RT-qPCR) or western blot (WB) analysis. ß-catenin nuclear localization was examined by western blotting and confocal microscopy. RESULTS: NOCA exhibited no significant cytotoxicity at concentrations below 20 µM and effectively inhibited H2O2-induced OS in PDLSCs. NOCA also restored ALP activity, mineralized nodule formation, and the expression of osteogenic markers in H2O2-stimulated PDLSCs. Mechanistically, NOCA increased p-ERK level and promoted ß-catenin translocation into the nucleus; however, blocking ERK pathway disrupted the osteogenic protection provided by NOCA and impaired its ability to induce ß-catenin nuclear translocation under OS conditions in PDLSCs. CONCLUSIONS: NOCA protected PDLSCs against H2O2-induced OS and effectively restored impaired osteogenic differentiation in PDLSCs by modulating the ERK/Wnt signaling pathway.

Outcomes Following Different Management of Mycotic Infrarenal Abdominal Aortic Aneurysms.

OBJECTIVE: The objective was to present our experience on managing mycotic infrarenal abdominal aortic aneurysm (MIAAA) through a retrospective cohort study. METHODS: Data of patients with MIAAA managed in our center from July 2016 to October 2022 were retrospectively analyzed. The diagnosis of MIAAA was made based on: (1) preoperative clinical signs of infection; (2) elevated serologic infection parameters; (3) para-aneurysmal infection features on enhanced computed tomography; and (4) positive blood or tissue cultures. All the patients received standard antibiotic therapy. Surgical management including endovascular aneurysm repair (EVAR), initial EVAR followed by open re-operation, and initial open surgical repair (OSR) were conducted according to disease seriosity, physical condition, and patient's will. Infection index and clinical outcome were evaluated during the follow-up time. RESULTS: A total of 23 patients (21 men; averaged=66.3 years, range=49-79 years) were included, with a mean follow-up time of 19.9 months (range=1-75 months). Bacteria culture from blood or tissue specimen was positive in 15 patients (Salmonella, n=8; Escherichia coli, n=3; methicillin-sensitive Staphylococcus aureus [MSSA], n=1; Klebsiella pneumoniae, n=1; Staphylococcus epidermidis, n=1; Mycobacterium tuberculosis, n=1). Seven patients received OSR as the initial surgical intervention, whereas 14 patients chose EVAR instead. The 2 conservatively managed patients (refused surgery) died within 30 days. The 7 patients who received initial OSR survived till now. Among the 14 patients who underwent initial EVAR, infection deteriorated without exception (14/14, 100%). Three of these patients refused re-operation and died within 6 months. Eleven patients received secondary surgical intervention (10 cases of aneurysm and endograft resection, thorough debridement, subclavian to bi-femoral artery bypass, or in situ aorta reconstruction; 1 case of laparoscopic debridement) and 7 survived the follow-up time. The overall mortality rate was 39.1% (9/23). The mortality rates differed greatly following different intervention methods (merely antibiotic management, 100%; initial open operation, 0%; initial EVAR without secondary operation, 100%; initial EVAR plus secondary operation, 36.4%). CONCLUSIONS: Open surgical repair is still the first choice for hemodynamically stable and low-risk patients. Merely EVAR is related with disastrous results, which should be reserved as a temporary alternative for patients with ruptured aneurysms, hemodynamic instability or high surgical risk, and followed by timely secondary OSR. CLINICAL IMPACT: The management of mycotic or primary-infected aortic aneurysm is challenging; treatment remains controversial. Our center has reviewed our experience over the past 6 years and found that open surgical repair is still the first choice for hemodynamically stable and low-risk patients. Merely endovascular aneurysm repair (EVAR) is related with disastrous results, which should be reserved as a temporary alternative for patients with ruptured aneurysms, hemodynamic instability or high surgical risk, and followed by timely secondary open surgical repair.

The PPAR-γ/SFRP5/Wnt/ß-catenin signal axis regulates the dexamethasone-induced osteoporosis.

BACKGROUND: The inhibition of glucocorticoid (GC) on osteoblastic differentiation of bone marrow stromal stem cells (BMSC) is an important pathway for GC to reduce bone formation. Recent studies implicated an important role of peroxisome proliferator-activated receptor-gamma (PPAR-γ) in GC-mediated cell proliferation and differentiation. Thus, our purpose is to investigate the role of PPAR-γ in regulating rat BMSC (rBMSC) osteoblastic differentiation. METHODS: The rBMSC treated with dexamethasone (Dex) was used to construct an in vitro cell model of GC-induced osteoporosis. The expressions of PPAR-γ, RUNX2, ALP, OPN and SFRP5 in cells were detected by RT-qPCR and western blot assays. Osteogenic differentiation of rBMSC was measured by Alizarin Red S (ARS) staining analysis. Lentivirus-delivered shRNA was used to knock down PPAR-γ or SFRP5, and lentivirus-delivered constructs were used to overexpress SFRP5 in rBMSC to verify the effect of PPAR-γ or SFRP5 on cell osteogenic differentiation. RESULTS: Dex significantly reduced rBMSC osteoblastic differentiation. The expression of PPAR-γ was enhanced in Dex treated rBMSC. PPAR-γ down-regulation improved Dex inhibition of rBMSC osteogenic differentiation. Moreover, PPAR-γ knockdown promoted protein levels of RUNX2, ALP, OPN and Dex-decreased rBMSC osteogenic differentiation. The expression of SFRP5 was reduced while Wnt and ß-catenin were increased in PPAR-γ knockdown and Dex treated rBMSC. Moreover, the up-regulation of SFRP5 reversed the osteogenic differentiation of rBMSC induced by PPAR-γ knockdown. CONCLUSION: These data indicated that in GC-induced osteoporosis, PPAR-γ/SFRP5 affects osteogenic differentiation by regulating the Wnt/ß-catenin signaling pathway.

Impact of Plaque Calcification and Stent Oversizing on Clinical Outcomes of Atherosclerotic Femoropopliteal Arterial Occlusive Disease Following Stent Angioplasty.

OBJECTIVE: Plaque calcification and stent oversizing are two key factors contributing to in stent restenosis (ISR) following femoropopliteal stent angioplasty. This study aimed to explore a pre-operative quantitative assessment method of plaque calcification and rational parameters of stent oversizing in the femoropopliteal artery. METHODS: A total of 115 patients with atherosclerotic femoropopliteal arterial occlusive disease treated from January 2013 to January 2016 were included retrospectively. Computed tomography angiography (CTA) imaging was performed to analyse calcified plaque parameters (calcified plaque volume [CV], standard CV [SCV], burden of calcified plaque) and stent oversizing parameters at different vessel segments (distal oversizing, maximum oversizing, plaque oversizing). Optimal cut offs for the six parameters were determined by the maximum Youden's index. The relationship between calcified plaque, stent oversizing, and clinical outcomes were assessed by correlation analysis and multivariable Cox regression models. RESULTS: The one year primary patency rate was 77.4%; the rates of ISR, major amputation, target lesion revascularisation, and mortality were 40.9%, 8.7%, 17.4%, and 12.2%, respectively. For all six parameters, patients with values greater than the cut offs had a significantly higher incidence of ISR than those with values below the cut offs. ISR was positively correlated with all six calcification and oversizing parameters. Amputation and mortality were positively correlated with calcification parameters. Multivariable Cox regression analysis demonstrated that all six parameters were independent risk factors for ISR. All calcification parameters were identified as independent risk factors for amputation, while only CV and SCV were independent risk factors for mortality. CONCLUSION: Calcified plaque in the femoropopliteal artery can be quantitatively analysed on pre-operative CTA images. High calcified plaque burden and excessive stent oversizing were associated with unfavourable outcomes following stent angioplasty.