The Role of Macrophage Efferocytosis in the Pathogenesis of Apical Periodontitis.

Macrophages (Mφs) play a crucial role in the homeostasis of the periapical immune micro-environment caused by bacterial infection. Mφ efferocytosis has been demonstrated to promote the resolution of multiple infected diseases via accelerating Mφ polarization into M2 type. However, the Mφ efferocytosis-apical periodontitis (AP) relationship has not been elucidated yet. This study aimed to explore the role of Mφ efferocytosis in the pathogenesis of AP. Clinical specimens were collected to determine the involvement of Mφ efferocytosis in the periapical region via immunohistochemical and immunofluorescence staining. For a further understanding of the moderator effect of Mφ efferocytosis in the pathogenesis of AP, both an in vitro AP model and in vivo AP model were treated with ARA290, a Mφ efferocytosis agonist. Histological staining, micro-ct, flow cytometry, RT-PCR and Western blot analysis were performed to detect the inflammatory status, alveolar bone loss and related markers in AP models. The data showed that Mφ efferocytosis is observed in the periapical tissues and enhancing the Mφ efferocytosis ability could effectively promote AP resolution via facilitating M2 Mφ polarization. Collectively, our study demonstrates the functional importance of Mφ efferocytosis in AP pathology and highlights that accelerating Mφ efferocytosis via ARA290 could serve as an adjuvant therapeutic strategy for AP.

SorCS2 is involved in promoting periodontitis-induced depression-like behaviour in mice.

BACKGROUND: Emerging evidence supports the association between periodontitis and depression, although the mechanisms are unclear. This study investigated the role of SorCS2 in the pathogenesis of periodontitis-induced depression. MATERIALS AND METHODS: An experimental periodontitis model was established using SorCS2 knockout mice and their wild-type littermates, and depression-like behaviour was evaluated. The expression of proBDNF signalling, neuronal activity, and glutamate-associated signalling pathways were further measured by western blotting and immunofluorescence. In addition, neuroinflammatory status, astrocytic and microglial markers, and the expression of corticosterone-related factors were measured by immunofluorescence, western blotting, and enzyme-linked immunosorbent assays. RESULTS: SorCS2 deficiency alleviated periodontitis-induced depression-like behaviour in mice. Further results suggested that SorCS2 deficiency downregulated the expression of pro-BDNF and glutamate signalling and restored neuronal activities in mice with periodontitis. Neuroinflammation in the mouse hippocampus was triggered by experimental periodontitis but was not affected by SorCS2 deficiency. The levels of corticosterone and the expression of glucocorticoid receptors were also not altered. CONCLUSION: Our study, for the first time, reveals the critical role of SorCS2 in the pathogenesis of periodontitis-induced depression. The underlying mechanism involves proBDNF and glutamate signalling in the hippocampus, providing a novel therapeutic target for periodontitis-associated depression.

Spatial and single-cell analyses uncover links between ALKBH1 and tumor-associated macrophages in gastric cancer.

BACKGROUND: AlkB homolog 1, histone H2A dioxygenase (ALKBH1), a crucial enzyme involved in RNA demethylation in humans, plays a significant role in various cellular processes. While its role in tumor progression is well-established, its specific contribution to stomach adenocarcinoma (STAD) remains elusive. This study seeks to explore the clinical and pathological relevance of ALKBH1, its impact on the tumor immune microenvironment, and its potential for precision oncology in STAD. METHODS: We adopted a comprehensive multi-omics approach to identify ALKBH1 as an potential diagnostic biomarker for STAD, demonstrating its association with advanced clinical stages and reduced overall survival rates. Our analysis involved the utilization of publicly available datasets from GEO and TCGA. We identified differentially expressed genes in STAD and scrutinized their relationships with immune gene expression, overall survival, tumor stage, gene mutation profiles, and infiltrating immune cells. Moreover, we employed spatial transcriptomics to investigate ALKBH1 expression across distinct regions of STAD. Additionally, we conducted spatial transcriptomic and single-cell RNA-sequencing analyses to elucidate the correlation between ALKBH1 expression and immune cell populations. Our findings were validated through immunohistochemistry and bioinformatics on 60 STAD patient samples. RESULTS: Our study unveiled crucial gene regulators in STAD linked with genetic variations, deletions, and the tumor microenvironment. Mutations in these regulators demonstrated a positive association with distinct immune cell populations across six immune datasets, exerting a substantial influence on immune cell infiltration in STAD. Furthermore, we established a connection between elevated ALKBH1 expression and macrophage infiltration in STAD. Pharmacogenomic analysis of gastric cancer cell lines further indicated that ALKBH1 inactivation correlated with heightened sensitivity to specific small-molecule drugs. CONCLUSION: In conclusion, our study highlights the potential role of ALKBH1 alterations in the advancement of STAD, shedding light on novel diagnostic and prognostic applications of ALKBH1 in this context. We underscore the significance of ALKBH1 within the tumor immune microenvironment, suggesting its utility as a precision medicine tool and for drug screening in the management of STAD.

Multi-Omics Reveals the Role of Osteopontin/Secreted Phosphoprotein 1 in Regulating Ovarian Aging.

Secreted phosphoprotein 1 (SPP1), also known as osteopontin (OPN), is located on chromosome 4q22.1. This multifunctional secreted acidic glycoprotein is expressed intracellularly and extracellularly in various tissues, where it interacts with regulatory proteins and pro-inflammatory immune chemokines, contributing to the pathogenesis of multiple diseases. Nevertheless, the intricate genetic connections between SPP1 and ovarian aging remain largely unexplored. This study aims to bridge this knowledge gap by delving into ovarian aging and its associations with SPP1 using multi-omics data analysis. Our findings indicate that SPP1 is a potential gene related to ovarian aging. To comprehend the role of SPP1, we conducted spatial transcriptomic analyses on young and aged female mouse ovaries, revealing a significant decline in SPP1 expression in the aging group compared to the young group. Similarly, a significantly low level of SPP1 was found in the 73-year-old sample. Additionally, in-depth single-cell RNA-sequencing analysis identified associations between SPP1 and ITGAV, ITGB1, CD44, MMP3, and FN1. Notably, co-expression analysis highlighted a strong correlation between SPP1 and ITGB1. In summary, this study pioneers the identification of SPP1 as a gene implicated in ovarian aging. Further research into the role of SPP1 has the potential to advance precision medicine and improve treatment strategies for ovarian aging-related conditions.

Severe inflammatory disorder in trisomy 8 without myelodysplastic syndrome and response to methylprednisolone: A case report.

BACKGROUND: Patients with trisomy 8 consistently present with myeloid neoplasms and/or auto-inflammatory syndrome. A possible link between myelodysplastic syndromes (MDS) with trisomy 8 (+8-MDS) and inflammatory disorders is well recognized, several cases having been reported. However, inflammatory disorders in patients without MDS have been largely overlooked. Generally, Behçet's disease is the most common type in +8-MDS. However, inflammatory disorders with pulmonary involvement are less frequent, and no effective treatment has been established. CASE SUMMARY: A 27-year-old man with recurrent fever, fatigue for > 2 mo, and unconsciousness for 1 day was admitted to our emergency department with a provisional diagnosis of severe pneumonia. Vancomycin and imipenem were administered and sputum collected for metagenomic next-generation sequencing. Epstein-Barr virus and Mycobacterium kansasii were detected. Additionally, chromosomal analysis showed duplications on chromosome 8. Two days later, repeat metagenomic next-generation sequencing was performed with blood culture. Cordyceps portugal, M. kansasii, and Candida portugal were detected, and duplications on chromosome 8 confirmed. Suspecting hematological disease, we aspirated a bone marrow sample from the iliac spine, examination of which showed evidence of infection. We added fluconazole as further antibiotic therapy. Seven days later, the patient's condition had not improved, prompting addition of methylprednisolone as an anti-inflammatory agent. Fortunately, this treatment was effective and the patient eventually recovered. CONCLUSION: Severe inflammatory disorders with pulmonary involvement can occur in patients with trisomy 8. Methylprednisolone may be an effective treatment.

Glycolytic reprogramming controls periodontitis-associated macrophage pyroptosis via AMPK/SIRT1/NF-κB signaling pathway.

Glycolysis has been demonstrated as a crucial metabolic process in bacteria infected diseases via modulating the activity of pyroptosis. Macrophages are the most abundant immune cells that infiltrated in the infected periodontal tissues, which significantly influence the outcome of periodontitis (PD). However, the effect of glycolysis in regulating macrophage pyroptosis during PD development remains unknown. This study aimed to explore the role of glycolysis in PD-associated macrophage pyroptosis and periodontal degeneration. Clinical specimens were used to determine the emergence of macrophage pyroptosis and glycolysis in periodontal tissues by immunohistochemical analysis and western blot. For an in-depth understanding of the regulatory effect of glycolysis in the progression of macrophage pyroptosis associated periodontitis, both in vivo PD model and in vitro PD model were treated with 2-DG (2-Deoxy-d-glucose), a glycolysis inhibitor. The data showed that the blockade of glycolysis could significantly suppress the lipopolysaccharide (LPS) induced macrophage pyroptosis, resulting in an attenuation of the inflammatory response and bone resorption in periodontal lesions. Furthermore, we revealed that the regulatory effect of glycolysis on macrophage pyroptosis can be mediated via AMPK/SIRT1/NF-κB signaling pathway. Our study unveiled that suppressed glycolysis restrains the activity of PD-associated macrophage pyroptosis, osteoclastogenesis, and subsequent periodontal tissue destruction. These findings extend our knowledge of glycolysis in regulating PD-associated macrophage pyroptosis and provide a potential novel target for PD therapy.

Early prediction of 30- and 14-day all-cause unplanned readmissions.

BACKGROUND: An unplanned readmission is a dual metric for both the cost and quality of medical care. METHODS: We employed the random forest (RF) method to build a prediction model using a large dataset from patients' electronic health records (EHRs) from a medical center in Taiwan. The discrimination abilities between the RF and regression-based models were compared using the areas under the ROC curves (AUROC). RESULTS: When compared with standardized risk prediction tools, the RF constructed using data readily available at admission had a marginally yet significantly better ability to identify high-risk readmissions within 30 and 14 days without compromising sensitivity and specificity. The most important predictor for 30-day readmissions was directly related to the representing factors of index hospitalization, whereas for 14-day readmissions the most important predictor was associated with a higher chronic illness burden. CONCLUSIONS: Identifying dominant risk factors based on index admission and different readmission time intervals is crucial for healthcare planning.

ProBDNF signaling is involved in periodontitis-induced depression-like behavior in mouse hippocampus.

OBJECTIVE: Increasing evidence supports the association between periodontitis and depression. However, the specific mechanisms remain to be further elucidated. The present study aimed to mechanistically investigate the regional roles of proBDNF (the precursor of brain-derived neurotrophic factor) in periodontitis induced depression-like behavior in mice. METHODS: Experimental periodontitis model was established by periodontal injection of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) in 8-week-old male Bdnf-HA/HA mice for 3 weeks. The depression-like behaviors, spontaneous exploratory activity and the level of anxiety were assessed by behavior tests. The activation of microglia and astrocytes, as well as the expression of Interleukin (IL)-1ß and Tumor necrosis factor (TNF)-α in the hippocampus, prefrontal cortex, and cortex were further assessed by immunofluorescence and western blots. The levels of IL-1ß in blood serum and expression of occludin as well as claudin5 in the hippocampus, prefrontal cortex, and cortex were further determined by enzyme-linked immunosorbent assay and western blot. Finally, the expression of proBDNF, its receptors, and mature BDNF (mBDNF), as well as neuronal activity were measured by western blots and immunofluorescence. RESULTS: Pg-LPS successfully induced periodontitis in mice and caused obvious depression-like behavior. Furthermore, we observed an increased activation of astrocytes and microglia, as well as a significant increase in expression of IL-1ß and TNF-α in the hippocampus of mice treated with Pg-LPS, with elevated level of IL-1ß in serum and decreased expression of occludin and claudin5 in the hippocampus. Importantly, we found that the levels of proBDNF and its receptors, SorCS2 and p75NTR, were increased significantly; however, the level of mBDNF was decreased, therefor leading to greater ratio of proBDNF/mBDNF. In addition, we also detected decreased neuronal activity in the hippocampus of mice treated with Pg-LPS. CONCLUSIONS: Our results indicate that Pg-LPS-induced periodontitis could cause depression-like behaviors in mice, and the proBDNF signaling is involved in the process.

Stress hyperglycemia ratio and neutrophil to lymphocyte ratio are reliable predictors of new-onset atrial fibrillation in patients with acute myocardial infarction.

Background: The occurrence of new-onset atrial fibrillation (NOAF) post-acute myocardial infarction (AMI) is associated with worse outcomes. In this study, we sought to assess the predictive effect of stress hyperglycemia ratio (SHR) and neutrophil to lymphocyte ratio (NLR) to predict NOAF in patients with AMI. Materials and methods: We recruited 3,194 individuals with AMI but free of atrial fibrillation (AF). AMI cases were stratified into groups according to SHR and NLR quartiles and were further categorized based on diabetes status. High SHR and high NLR were defined as the highest quartile of SHR and NLR. A nomogram incorporating risk factors for NOAF was constructed using multivariate logistic regression analyses. The performance of the novel nomogram was tested for predictive performance, agreement between the actual and predicted probability, and clinical utility using area under the curve (AUC), bootstrapped calibration curves, and decision curve analysis, respectively. Result: A total of 245 (7.67%) patients developed NOAF post-AMI. The NOAF cases had higher values of SHR and NLR than non-NOAF patients after AMI regardless of diabetes status. After adjusting for potential confounders, high SHR and NLR were independently associated with NOAF post-AMI. Moreover, the novel nomogram incorporating high NLR and high SHR for NOAF risk estimation in patients with AMI showed satisfactory performance assessed by the AUC, calibration curves, decision curve analysis. Conclusion: SHR and NLR were independently associated with NOAF in AMI patients. The constructed novel nomogram that incorporates SHR and NLR might assist in NOAF risk stratification post-AMI.

Development and Validation of a Nomogram for Estimation of Left Atrial Thrombus or Spontaneous Echo Contrast Risk in Non-Valvular Atrial Fibrillation Patients with Low to Borderline CHA2DS2-VASc Score.

Purpose: Left atrial thrombus (LAT)/left atrial spontaneous echo contrast (LASEC) still exists in CHA2DS2-VASc score-defined low/borderline risk population. The purpose of this study is to explore the risk factors that associate with LAT/SEC and to create a nomogram to predict LAT/SEC risk in NVAF patients with low/borderline CHA2DS2-VASc scores. Patients and Methods: A total of 834 NVAF patients with complete data on transesophageal echocardiography (TEE) were included in this study. Univariate and multivariate logistic regression analyses were performed to identify the risk factors that associate with LAT/SEC, and a nomogram was established based on the results. Receiver operating characteristic curve (ROC), calibration curve and decision curve analysis were performed to verify the predictive power of nomogram. Results: The rates for LAT/SEC for the training and validation cohorts were 84 (14.7%) and 30 (11.4%), respectively. Independent factors including age, left ventricular ejection fraction (LVEF), left atrial diameter (LAD), smoke, non-paroxysmal AF (NPAF), and E/e' were considered to construct the nomogram for LAT/SEC. The AUC for nomogram was 0.839 and 0.811 in the training and validation cohorts, respectively. The calibration and decision curve analysis showed that the nomogram had a good prediction capacity and would be clinically useful. Conclusion: Age, LVEF, LAD, smoke, NPAF, and E/e' are independently associated with LAT/SEC in NVAF patients with low/borderline CHA2DS2-VASc scores. The nomogram that incorporates these six variables effectively predict LAT/SEC risk in NVAF patients with low/borderline CHA2DS2-VASc scores.

Gremlin aggravates periodontitis via activation of the nuclear factor-kappa B signaling pathway.

BACKGROUND: Gremlin has been reported to regulate inflammation and osteogenesis. Periodontitis is a destructive disease degenerating periodontal tissues, therefore leads to alveolar bone resorption and tooth loss. Based on the importance of Gremlin's bio-activity, the aim of this study is to, in vivo and in vitro, unveil the function of Gremlin in regulating the development of periodontitis and its consequent effects on alveolar bone loss. METHODS: Clinical specimens were used to determine the expression of Gremlin in periodontal tissues by immunohistochemical staining and western blot. Then utilizing the rat periodontitis model to investigate the function of gremlin-regulated nuclear factor-kappa B (NF-κB) pathway during the development of periodontal inflammation and the alveolar bone loss. Last, the regulation of the osteogenesis of human periodontal ligament stem cells (hPDLSCs) by Gremlin under inflamed condition was analyzed by alkaline phosphatase (ALP) and alizarin red staining (ARS). RESULTS: We found clinically and experimentally that the expression of Gremlin is markedly increased in periodontitis tissues. Interestingly, we revealed that Gremlin regulated the progress of periodontitis via regulating the activities of NF-κB pathway and interleukin-1ß (IL-1ß). Notably, we observed that Gremlin influenced the osteogenesis of hPDLSCs. Thus, our present study identified Gremlin as a new key regulator for development of periodontitis. CONCLUSIONS: Our current study illustrated that Gremlin acts as a crucial mediator and possibly serves as a potential diagnostic marker for periodontitis. Discovery of new factors involved in the pathophysiology of periodontitis could contribute to the development of novel therapeutic treatment for the disease.

Holiday ratio of hospitalization and 30-day readmission rates among cancer patients after major surgery.

BACKGROUND: To determine the association of 30-day readmission with weekend discharge and the number of holiday days during a hospital stay (holiday ratio). METHODS: This retrospective cohort study used the clinical research database and cancer registry data of our hospital from January 1, 2011 to December 31, 2017. Patient characteristics, tumor factors, clinical laboratory data, and proxies of continuity of care, such as weekend discharge or holiday ratio (holiday days/total hospitalization days), received statistical analysis. Multivariate logistic regression identified the independent factors for 30-day potentially avoidable readmission rate (PAR). RESULTS: Of 1433 patients receiving tumor resection, 520 (36.29%) had colon cancer; 440 (30.70%) had head and neck cancer (HNC), and 473 (33.01%) had other cancers (lung, liver, and prostate). The rate of 30-day PAR was 6.3% for those with colon cancer, 8.6% for HNC, and 3.6% for other cancers. The 30-day PAR did not significantly differ by discharge on a weekend versus weekday for those with colon cancer (8.33% vs. 5.90%; p = 0.379), HNC (7.06% vs. 9.01%; p = 0.566), or other cancers (0.00% vs. 4.28%; p = 0.960). Colon cancer patients with holiday ratio >0.3 had a higher readmission rate (9.58% vs. 4.82%, p = 0.041). In multivariate analysis, a holiday ratio >0.3 (adjusted odds ratio 2.16; 95% Confidence Interval, 1.05-4.39) in those with colon cancer was an independent predictor of 30-day PAR. CONCLUSIONS: Weekend discharge after major surgery did not affect 30-day readmission rates in cancer patients, but the holiday ratio did affect 30-day PAR for those with colon cancer.

Older veterans associated with reduced risk of cancer: Retrospective nationwide matched cohort study in Taiwan.

Importance: It remains unknown whether Taiwanese veterans have a lower risk of subsequent cancer compared with non-veterans. Objective: To examine whether veterans are associated with reduced cancer risk. Methods: From January 2004 to December 2017, this study included 957 veterans and 957 civilians who were propensity score (PS) matched by years of birth, sex, residence, index year, days in the hospital, frequency of outpatient visits, and relevant comorbidities at baseline. Multivariate Cox proportional hazards regression analysis was applied to compare the risks of cancer, overall and by subgroup, and mortality. All the participants were cancer free at the baseline. Exposures: Veterans retrieved from Taiwan National Health Insurance Research Database (NHIRD). Main outcome: Cancer extracted from the Registry for Catastrophic Illness Patients Database (RCIPD). Results: Overall, 1,914 participants were included, and 957 veterans with a mean (SD) age of 75.9 (6.79) years and 946 men (98.9%). The mean follow-up was about 10.5 (±4.51) years. Cancer was recorded in 6.68% (N = 64) and 12.12% (N = 116) of veterans and non-veterans, respectively. Veterans were associated with decreased risk [adjusted hazard ratio (aHR), 0.57; 95% CI: 0.41-0.78; P < 0.001] of cancer compared with civilians after controlling for age, sex, urbanization, hypertension, diabetes, hyperlipidemia, cardiovascular event, COPD, asthma, chronic liver disease, alcohol-related illness, and Parkinson's disease. Cancer subgroup analyses verified this finding (HRs <1.0). The decreased incidence rate was predominantly for liver cancer (aHR, 0.18; 95% CI: 0.05-0.72; P < 0.05). Conclusion: Taiwanese older veterans are associated with reduced overall cancer risk than individuals without veteran status.

Using Healthcare Complaints Analysis Tool to Evaluate Patient Complaints during the COVID-19 Pandemic at a Medical Center in Taiwan.

The purpose of this study is to evaluate patient complaints using the Healthcare Complaints Analysis Tool (HCAT) during the COVID-19 pandemic in 2021 in Taiwan. Additionally, the study examines the distribution and type of patient complaints before and during the COVID-19 pandemic to provide a better clinical procedure, hospital management and patient relationship. This study utilizes a cross-sectional design. We collected patient complaints from January 2021 to December 2021 at a medical center in Southern Taiwan. Using the Healthcare Complaints Analysis Tool (HCAT), the patient complaints are classified and coded into three major domains (clinical, management and relationship), and seven problem categories (quality, safety, environment, institutional process, respect and patient rights, listening and communication). We further compared and categorized the complaints based on whether they were COVID-19-related or not and whether it was before or during the COVID-19 pandemic to understand the differences in patient complaints. In total, we collected 584 events of patient complaints. Based on the HCAT domains, the complaints about management were the highest, at 52.9%, followed by complaints about relationship, about 37.7%. According to the types of problem, the complaints about the environment were the highest, about 32.5% (190/584), followed by communication at about 29.6% (173/584), and institutional process at about 20.4% (119/584). There were 178 COVID-19-related complaints and they were made more frequently during Q3 and Q4 (from mid-June to December) which was the pandemic period in 2021 in Taiwan. Among the COVID-19-related complaints, the most frequent were in the environment domain with 114 cases (about 65.7% of COVID-19-related complaints). The domains of patient complaints were statistically different between COVID-19-related and non-related (p < 0.001). During the COVID-19 pandemic, the proportion of COVID-19-related complaints increased 1.67 times (117/312 vs. 61/272, p < 0.001). Both prior to and during the COVID-19 pandemic, management-related complaints represented the highest domain. During the COVID-19 pandemic, the implementation of infectious disease prevention and control policies and actions may have developed some inconvenience and difficulty in seeking medical practice and process. These characteristics (complaints) are more prominent, and timely and patient-first consideration is required immediately to build up better clinical procedures, the healthcare environment and comprehensive communication. Using the HCAT can allow health centers or health practitioners to understand the needs and demands of patients through complaints, provide friendly medical and health services, avoid unequal information transmission, build trust in doctor−patient relationships and improve patients' safety.

Comparison of Back-Propagation Neural Network, LACE Index and HOSPITAL Score in Predicting All-Cause Risk of 30-Day Readmission.

BACKGROUND: The main purpose of this study is to predict the all-cause risk of 30-day readmission by employing the back-propagation neural network (BPNN) in comparison with traditional risk assessment tools of LACE index and HOSPITAL scores. METHODS: This was a retrospective cohort study from January 1st, 2018 to December 31st, 2019. A total of 55,688 hospitalizations from a medical center in Taiwan were examined. The LACE index (length of stay, acute admission, Charlson comorbidity index score, emergency department visits in previous 6 months) and HOSPITAL score (hemoglobin level at discharge, discharge from an Oncology service, sodium level at discharge, procedure during hospital stay, Index admission type, number of hospital admissions during the previous year, length of stay) are calculated. We employed variables from LACE index and HOSPITAL score as the input vector of BPNN for comparison purposes. RESULTS: The BPNN constructed in the current study has a considerably better ability with a C statistics achieved 0.74 (95% CI 0.73 to 0.75), which is statistically significant larger than that of the other two models using DeLong's test. Also, it was possible to achieve higher sensitivity (70.32%) without penalizing the specificity (71.76%) and accuracy (71.68%) at its optimal threshold, which is at the 20% of patients with the highest predicted risk. Moreover, it is much more informative than the other two methods because of a considerably higher LR+ and a lower LR-. CONCLUSION: Our findings suggest that more attention should be paid to methods based on non-linear classification systems, as they lead to substantial differences in risk-scores.

Crosstalk between Wnt/ß-catenin signaling and NF-κB signaling contributes to apical periodontitis.

In physiology conditions, the crosstalk of signaling pathways has been considered to extend the functions of individual pathways and results in a more complex regulatory network. The Wnt3a/ß-catenin and NF-κB signaling pathways have been demonstrated involving in apical periodontitis (AP). As AP progresses, ultimately causes tooth loss. In the present study, we investigate the contribution of the crosstalk between the Wnt3a/ß-catenin and NF-κB signaling pathways to the development of AP. Clinically, utilizing 60 human AP and healthy tissues (30 samples for each group), we found that the expression levels of Wnt3a/ß-catenin and NF-κB were elevated in the Ap tissues compared to that in the healthy group. To further study the roles of Wnt3a/ß-catenin and NF-κB signaling pathways in the development of AP, and the contribution of the crosstalk between these two signaling pathways to AP, we established the AP animal model and observed that, first, both pathways are activated in the AP group compared to the control group. Interestingly, by immunoprecipitation and western blot experiments, we revealed that there is greater interaction between NF-κB (phorspho-p65) and ß-catenin in AP tissues compared to the control tissues. Importantly, when the NF-κB signaling pathway was blocked by its inhibitor, pyrrolidine dithiocarbamate (PDTC), the activity of the Wnt3a/ß-catenin signaling pathway was abolished, and consequently led to the attenuation of the inflammation response in LPS-induced human periodontal ligament cells (hPDLCs). Thus, our data indicate that the crosstalk between Wnt3a/ß-catenin and NF-κB signaling pathway contributes to the development of AP, and provide a therapeutic strategy for the treatment of AP as well.

Stronger inhibitory effects of Ticagrelor plus aspirin compared with Clopidogrel plus aspirin on arachidonic acid-induced platelet aggregation in patients with acute coronary syndrome with PCI.

Antagonists of the Adenosine Diphosphate (ADP) receptor, P2Y12, may inhibit platelet aggregation as a result of stimulation with arachidonic acid (AA). The potent P2Y12 blocker, Ticagrelor has greater anti-platelet effects than Clopidogrel. We explored the effects of Ticagrelor versus Clopidogrel on mean maximum aggregation ratios (MAR%) in response to AA stimulation in patients receiving aspirin in conventional doses. A total of 613 acute coronary syndrome (ACS) patients were followed from October 2017 to October 2018. At the one- and six-month follow-up visit, mean AA-MAR% was lower in the Ticagrelor group when compared with the Clopidogrel group (28.9% vs 31.7%, 28.4% vs 31.0%, p<0.001 and p=0.001, respectively). BARC1-2 bleeding occurred with greater frequency with Ticagrelor than in patients treated with Clopidogrel (29.3% vs 9.5%, p<0.001; 23.5% vs 9.3%, p<0.001). Excessive platelet inhibition and decreased AA-MAR% were considered the main reasons for the severe subcutaneous/dermal bleeding in Ticagrelor treated patients.