Accumulation of amyloid-β (Aβ) in the brain is a central component of pathology in Alzheimer's disease.A growing number of evidences demonstrate close associations between periodontal pathogens including Porphyromonas gingivalis (P. gingivalis) and Treponema denticola (T. denticola) and AD. However, the effect and mechanisms of T. denticola on accumulation of Aβ remain to be unclear. In this study, we demonstrated that T. denticola was able to enter brain and act directly on nerve cells resulting in intra and extracellular Aβ 1−40 and Aβ 1−42 accumulation in the hippocampus of C57BL/6 mice by selectively activating both β-secretase and γ-secretase. Furthermore, both KMI1303, an inhibitor of βsecretase, as well as DAPT, an inhibitor of γ-secretase were found to be able to inhibit the effect of T. denticola on Aβ accumulation in N2a neuronal cells. Overall, it is concluded that T. denticola increases the expression of Aβ 1−42 and Aβ 1−40 by its regulation on beta-site amyloid precursor protein cleaving enzyme-1 and Presenilin 1.
Background: NAD-dependent methylenetetrahydrofolate dehydrogenase catalyzes the conversion of 10-formyltetrahydrofolate to formate in embryonic and adult mammalian mitochondria.Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) is a folate cycle enzyme that is involved in the development of various diseases including cancer. However, the specific mechanisms in oral squamous cell carcinoma (OSCC) are unclear. We analyzed the functional routes of MTHFD1L in OSCC cells.Methods: MTHFD1L expression in OSCC was analyzed using data from The Cancer Genome Atlas (TCGA) database. Then, the levels of mRNA were measured in OSCC and para-tumor oral tissues using Affymetrix microarrays. Additionally, the effects of short hairpin RNA (shRNA)-induced MTHFD1L silencing on the biological behavior of OSCC were assessed in vitro and in vivo, and the potential molecular mechanisms underlying MTHFD1L activity were also investigated.Results: A TCGA database analysis of RNA sequencing revealed that MTHFD1L levels were higher in tumor tissue than in adjacent tissues. Immunohistochemical staining and Kaplan-Meier survival analysis also indicated that MTHFD1L upregulation is associated with a poor prognosis in OSCC. The knockdown of MTHFD1L suppressed cell proliferation, colony formation, and tumorigenesis, while it induced apoptosis in OSCC. Mechanistically, a microarray analysis showed that MTHFD1L suppressed c-MYC and activated p53 signaling by regulating the protein expression of TP53, GADD45A, FAS and JUN.Conclusions: MTHFD1L may be involved in OSCC progression via the c-MYC gene and p53 signaling and may serve as a novel target and orientation for tumor therapy.
The frequent refractory response of patients to the treatment of medication-related osteonecrosis of the jaw (MRJON) has attracted clinicians’ attention to several treatments. However, they are at best, palliative, and have a higher failure rate than previous treatments. The present meta-analysis was performed to evaluate the clinical effectiveness of autologous platelet concentrates (APCs) combined with surgery in the treatment of MRONJ. The authors conducted a meta-analysis involving a systematic search of PubMed, EMBASE, Wiley Online Library and the Cochrane Library for eligible studies from their inception to November 2019, in accordance with preselected criteria. The inverse variance method was applied to fixed or random effects models based on the heterogeneity of the studies. Thirteen studies that investigated APCs in the treatment of MRONJ were eligible for inclusion in the meta-analysis of 223 patients and 33 lesions. The pooled success rate of APCs combined with surgery for MRONJ was 90% (95%CI, 80%–97%) and the pooled OR was 7.67 (95%CI, 2.10–27.98), indicating the combination was 7.67 times more effective than surgery alone. The results suggest that the use of APCs is a promising therapeutic regimen, as it provided additional benefits to surgery in the treatment of MRONJ. To achieve the benefits, a tension-free primary closure of the soft tissue is recommended as well. Randomized studies with large sample sizes is warranted to confirm our finding.
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