Epidemiologic relationship between periodontitis and type 2 diabetes mellitus.

BACKGROUND: To systematically review the epidemiologic relationship between periodontitis and type 2 diabetes mellitus (T2DM). METHODS: Four electronic databases were searched up until December 2018. The manual search included the reference lists of the included studies and relevant journals. Observational studies evaluating the relationship between T2DM and periodontitis were included. Meta-analyses were conducted using STATA. RESULTS: A total of 53 observational studies were included. The Adjusted T2DM prevalence was significantly higher in periodontitis patients (OR = 4.04, p = 0.000), and vice versa (OR = 1.58, p = 0.000). T2DM patients had significantly worse periodontal status, as reflected in a 0.61 mm deeper periodontal pocket, a 0.89 mm higher attachment loss and approximately 2 more lost teeth (all p = 0.000), than those without T2DM. The results of the cohort studies found that T2DM could elevate the risk of developing periodontitis by 34% (p = 0.002). The glycemic control of T2DM patients might result in different periodontitis outcomes. Severe periodontitis increased the incidence of T2DM by 53% (p = 0.000), and this result was stable. In contrast, the impact of mild periodontitis on T2DM incidence (RR = 1.28, p = 0.007) was less robust. CONCLUSIONS: There is an evident bidirectional relationship between T2DM and periodontitis. Further well-designed cohort studies are needed to confirm this finding. Our results suggest that both dentists and physicians need to be aware of the strong connection between periodontitis and T2DM. Controlling these two diseases might help prevent each other's incidence.

Baseline HbA1c Level Influences the Effect of Periodontal Therapy on Glycemic Control in People with Type 2 Diabetes and Periodontitis: A Systematic Review on Randomized Controlled Trails.

INTRODUCTION: The question of whether periodontal therapy is an effective strategy for achieving glycemic control in people with type 2 diabetes mellitus (T2DM) and periodontitis continues to be open to debate. To clarify this issue, we conducted a systematic review and meta-analysis. METHODS: A systematic literature search of randomized controlled trials (RCTs) was carried out by searching four electronic databases and four journals up to April 2020. RCTs that evaluated the effect of periodontal therapy on glycemic control in people with T2DM were included. RESULTS: A total of 23 RCTs were included in this systematic review and meta-analysis. We found that after 3 and 6 months, periodontal therapy could significantly reduce glycosylated hemoglobin (HbA1c) level (3-month: weighted mean difference [WMD] - 0.514, 95% confidence interval [CI] - 0.730, - 0.298, p = 0.000; 6-month: WMD - 0.548, 95% CI - 0.859, - 0.238, p = 0.000). However, huge heterogeneity existed. Further analyses on 11 potential sources of heterogeneity found that baseline HbA1c of the included studies was the most significant factor causing heterogeneity. The benefit of periodontal therapy on glycemic control was much more obvious in studies with a higher baseline HbA1c level than in those with a lower baseline HbA1c level. CONCLUSIONS: Periodontal therapy significantly contributed to glycemic control in T2DM patients, especially in patients with higher baseline HbA1c level.

Nerve growth factor protects salivary glands from irradiation-induced damage.

AIMS: Radiotherapy has become a basic treatment modality for head and neck cancer. However, radiotherapy results in inevitable side effects, particularly radiation sialadenitis, that significantly impairs quality of life. A previous study indicated that nerve growth factor (NGF) has a radio-protective effect, but the mechanism was not determined in salivary glands. In this study, we explored the functional role and mechanism regarding how NGF protects salivary glands against IR-induced damage. MAIN METHODS: Human salivary gland (HSG) cells and C57BL/6 mice were selected to establish an IR-induced salivary gland damage model in vitro and in vivo. Recombinant NGF protein and NGF siRNA and over-expression plasmids were applied to manipulate NGF expression in vitro. AAV-NGF was retrogradely perfused into the submandibular gland (SMG) through the SMG duct to manipulate NGF expression in vitro. Small-molecule inhibitors and siRNAs were applied to inhibit AKT and JNK. Western blotting, quantitative PCR, flow cytometry and histology assays were performed to analyse the functional role and mechanism of NGF. KEY FINDINGS: Our study demonstrated that NGF expression was upregulated following radiotherapy both in human HSG cells and mouse SMG tissues. NGF could reduce IR-induced HSG cell apoptosis, and AAV-mediated gene therapy could restore the salivary flow rate and protect the salivary gland against IR-induced apoptosis in vivo. Mechanistically, NGF protects salivary glands from IR-induced apoptosis by de-phosphorylating JNK kinase rather than promoting AKT phosphorylation. SIGNIFICANCE: The current study findings indicated that the modulation of the NGF pathway might prevent IR-induced salivary hypo-function.

A novel nomogram based on SEER database for the prediction of liver metastasis in patients with small-cell lung cancer.

BACKGROUND: To establish and validate a nomogram to predict liver metastasis in patients with small-cell lung cancer (SCLC). METHODS: Information on patients diagnosed with SCLC between 2010 and 2015 was retrospectively retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Risk factors for liver metastasis were identified by logistic regression analyses to construct a nomogram. The predictive accuracy was evaluated by concordance indexes (c-index) and calibration plots, and the comparison of discrimination between the nomogram and other routine staging systems was achieved with the area under receiver operating characteristic curve (AUC) analysis. Decision curve analysis (DCA) was performed to measure the clinical performance of the nomogram. RESULTS: A total of 12,957 patients met our inclusion criteria and were randomly assigned to training (n=6,479) and validation (n=6,478) sets. The nomogram which was established based on independent clinicopathological factors had poor accuracy, and after other distant metastatic sites were added into the predictive model, the new nomogram displayed better discrimination power, with c-indexes of 0.703 in the training set and 0.712 in the validation set. Both internal and external calibration plots approached 45 degrees. The AUCs and net benefit of the predictive model were both higher than those of routine staging systems. CONCLUSIONS: The validated nomogram might be a practical tool for clinicians to quantify the risk of liver metastasis in patients with SCLC and improve cancer management.

Identification of key genes and pathways downstream of the ß-catenin-TCF7L1 complex in pancreatic cancer cells using bioinformatics analysis.

As a key component of the Wnt signaling pathway, the ß-catenin-transcription factor 7 like 1 (TCF7L1) complex activates transcription and regulates downstream target genes that serve important roles in the pathology of pancreatic cancer. To identify associated key genes and pathways downstream of the ß-catenin-TCF7L1 complex in pancreatic cancer cells, the current study used the gene expression profiles GSE57728 and GSE90926 downloaded from the Gene Expression Omnibus. GSE57728 is an array containing information regarding ß-catenin knockdown and GSE90926 was developed by high throughput sequencing to provide information regarding TCF7L1 knockdown. Subsequently, differentially expressed genes (DEGs) were sorted separately and the shared 88 DEGs, including 37 upregulated and 51 downregulated genes, were screened. Clustering analysis of these DEGs was performed by heatmap analysis. Functional and pathway enrichment analyses were then performed using FunRich software and Database for Annotation, Visualization and Integrated Discovery, which revealed that the DEGs were predominantly enriched in terms associated with transport, transcription factor activity, and cytokine and chemokine mediated signaling pathway process. A DEG-associated protein-protein interaction (PPI) network, consisting of 58 nodes and 171 edges, was then constructed using Cytoscape software and the 15 genes with top node degrees were selected as the hub genes. Overall survival (OS) analysis of the 88 DEGs was performed and the relevant gene expression datasets were downloaded from The Cancer Genome Atlas. Consequently, three upregulated and seven downregulated genes were identified to be associated with prognosis. Furthermore, high expression levels of five downregulated genes, including CXCL5, CYP27C1, FUBP1, CDK14 and TRIM24, were associated with worse OS. In addition, CDK14 and TRIM24 were revealed as hub genes in the PPI network and both were confirmed to be involved in the Wnt/ß-catenin pathway and phosphoinositide 3-kinase/Akt signaling pathway. Promoter analysis was also applied to the five downregulated DEGs associated with prognosis, which revealed that TCF7L1 may serve as a transcription factor of the DEGs. In conclusion, the genes and pathways identified in the current study may provide potential targets for the diagnosis and treatment of pancreatic cancer.

In Vitro and Clinical Studies of Gene Therapy with Recombinant Human Adenovirus-p53 Injection for Malignant Melanoma.

Malignant melanoma is an aggressive tumor with high fatality rates and poor prognosis, mainly due to the lack of efficient treatment methods. The present study investigated the potential antitumor effects of recombinant adenovirus p53 (rAd-p53) on human malignant melanoma. The optimal viral titer on a human malignant melanoma (A-375) cell line was determined for the rAd-p53 treatment. The invasive abilities, apoptosis, variations in the cell cycle, and molecular expression levels of A-375 cells were detected after infection by rAd-p53. A tumor growth curve and hematoxylin and eosin staining were carried out for experiments in nude mice. Twenty-one patients with malignant melanoma were evaluated, including 12 cases without gene therapy and nine cases with rAd-p53 gene therapy. The overall survival rate and the median survival time were analyzed between the two groups of patients. When the multiplicity of infection was 100, the cells showed the best transfection efficiency. The invasive ability, apoptosis, cycle changes of the cells, and the expression of the p53, p21, and Bax genes and proteins were significantly changed in the experimental group. In nude mice, the tumor growth curve and the tumor size in the experimental group were significantly smaller than those of the control group. Hematoxylin and eosin staining revealed tumor metastasis in the blank group and the control group but not in the experimental group. Between the two groups of patients, the median survival of the gene therapy group (38 months) was greater than that of the group without gene therapy (27 months). In this study, high expression of the p53 gene could regulate the gene expression and reduce the invasive and metastatic abilities of the tumor cells. Furthermore, rAd-p53 effectively improved the survival of patients with malignant melanoma. Therefore, rAd-p53 may be a potential treatment method for human malignant melanoma.