How Periodontitis or Periodontal Bacteria Can Influence Alzheimer's Disease Features? A Systematic Review of Pre-Clinical Studies.

BACKGROUND: The negative effects of periodontitis on systemic diseases, including diabetes, cardiovascular diseases, and Alzheimer's disease (AD), have been widely described. OBJECTIVE: This systematic review aimed to gather the current understanding of the pathophysiological mechanisms linking periodontitis to AD. METHODS: An electronic systematic search of the PubMed/MEDLINE, Scopus, and Embase databases was performed using the following PECO question: How can periodontitis or periodontal bacteria influence Alzheimer's disease features?". Only preclinical studies exploring the biological links between periodontitis and AD pathology were included. This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO), and the Syrcle and Camarades protocols were used to assess the risk of bias. RESULTS: After a systematic screening of titles and abstracts (n = 3,307), thirty-six titles were selected for abstract reading, of which 13 were excluded (k = 1), resulting in the inclusion of 23 articles. Oral or systemic exposure to periodontopathogens or their byproducts is responsible for both in situ brain manifestations and systemic effects. Significant elevated rates of cytokines and amyloid peptides (Aß) and derivate products were found in both serum and brain. Additionally, in infected animals, hyperphosphorylation of tau protein, hippocampal microgliosis, and neuronal death were observed. Exposure to periodontal infection negatively impairs cognitive behavior, leading to memory decline. CONCLUSIONS: Systemic inflammation and brain metastatic infections induced by periodontal pathogens contribute to neuroinflammation, amyloidosis, and tau phosphorylation, leading to brain damage and subsequent cognitive impairment.

One-stage versus two-stage piezocision-assisted orthodontic tooth movement: A preclinical study based on Nano-CT and RT-PCR analyses.

OBJECTIVE: To evaluate the effect of a second-stage piezocision on the biological response. MATERIALS AND METHODS: 60 rats were randomly allocated to 6 experimental groups of 10 rats. Rats undergoing a one-stage piezocision were sacrified on day 7, 28 and 42 (groups 1-3) while rats undergoing a two-satge piezocision were sacrified on day 42, 63 and 90 (groups 4-6), respectively. The biological response was investigated in 3D at the tissue level using Nano-computed tomography (Nano-CT) and, at the molecular level using the qRT-PCR technique. Bone Volume Fraction (BVF) loss was the primary endpoint. RESULTS: Similar loss of BVF were observed both after the first and second piezocisions. The change in BVF loss between 7 and 28 days after each piezocision were 25.1 ± 13.0 (SE)% and 11.2 ± 11.6 (SE)% respectively and did not differ from each other (p = 0.43). Changes in BVF loss from 7 to 42 days were also comparable in one-stage and two-stage piezocision (4.9 ± 12.3 (SE) vs. -19.9 ± 13.4 (SE), p = 0.19). At the molecular level, all parameters except Translating Ribosome Affinity Purification (TRAP) protein had identical patterns. CONCLUSION: Within the limits of the present study, a second piezocision allowed to re-induce the Regional Acceleratory Phenomenon (RAP) effect. Nevertheless, the relevance of the findings to the clinical effect has not been tested.

Human papillomavirus oncoproteins induce a reorganization of epithelial-associated γδ T cells promoting tumor formation.

It has been shown that γδ T cells protect against the formation of squamous cell carcinoma (SCC) in several models. However, the role of γδ T cells in human papillomavirus (HPV)-associated uterine cervical SCC, the third-leading cause of death by cancer in women, is unknown. Here, we investigated the impact of γδ T cells in a transgenic mouse model of carcinogenesis induced by HPV16 oncoproteins. Surprisingly, γδ T cells promoted the development of HPV16 oncoprotein-induced lesions. HPV16 oncoproteins induced a decrease in epidermal Skint1 expression and the associated antitumor Vγ5+ γδ T cells, which were replaced by γδ T-cell subsets (mainly Vγ6+ γδlowCCR2+CCR6-) actively producing IL-17A. Consistent with a proangiogenic role, γδ T cells promoted the formation of blood vessels in the dermis underlying the HPV-induced lesions. In human cervical biopsies, IL-17A+ γδ T cells could only be observed at the cancer stage (SCC), where HPV oncoproteins are highly expressed, supporting the clinical relevance of our observations in mice. Overall, our results suggest that HPV16 oncoproteins induce a reorganization of the local epithelial-associated γδ T-cell subpopulations, thereby promoting angiogenesis and cancer development.

Origin and immunoescape of uterine cervical cancer.

Human papillomavirus associated uterine cervical cancer is an important public health problem since it is classified as the fourth most common cancer in women worldwide with more than 500,000 recorded cases. This review is focused on where and why HPV infection induces cervical cancers and how this virus avoids the host immune response. Immunological therapeutic approaches are also addressed.