Metabolic alterations could profoundly affect immune functions and influence the progression and outcome of autoimmune diseases. However, the detailed mechanisms and their therapeutic potential remain to be defined. Here, we show that phosphatidylinositide 3-kinase interacting protein 1 (Pik3ip1), a newly identified negative immune regulator, is notably down-regulated in several major autoimmune diseases through a previously unidentified mechanism mediated by interleukin-21/p38 mitogen-activated protein kinase/a disintegrin and metalloprotease-17 (ADAM17) pathway. Down-regulation of Pik3ip1 in T cells causes a major metabolic shift from oxidative phosphorylation toward aerobic glycolysis, leading to their overactivation and aggressive disease progression in experimental autoimmune encephalomyelitis (EAE) mouse model. Suppression of hypoxia-inducible factor 1α (Hif1α) or pharmacologic inhibition of glycolysis could reverse these phenotypes and largely mitigate EAE severity. Our study reveals a previously unrecognized role of Pik3ip1 in metabolic regulation that substantially affects the inflammatory loop in the autoimmune setting and identifies the Pik3ip1/Hif1α/glycolysis axis as a potential therapeutic target for treatment of autoimmune diseases.
Objective A better understanding of the current characteristics of clinical trials in oral squamous cell carcinoma (OSCC) is important to improve trial design and identify neglected areas of research. The objective is to summarize the current characteristics and publication status of OSCC trials registered on ClinicalTrials.gov. Methods The ClinicalTrials.gov database was searched on November 9, 2020, for trials containing the term “oral squamous cell carcinoma”. We assessed the characteristics of the included trials and searched the publication status of the primary completed trials by using PubMed and Google Scholar. Results Our search identified 325 studies for analysis, including 279 interventional (85.8%) and 46 observational (14.2%) studies. Interventional studies were mostly single-group (50.9%), single-center (57.0%), non-randomized (59.1%), open-label (81.4%), and early-phase (70.6%) trials. The vast majority of the studies (82.8%) focused on the treatment of OSCC. Chemotherapy (36.8%) was the most common treatment, followed by targeted therapy (15.2%) and immunotherapy (15.2%). Furthermore, 58.9% of the primary completed interventional studies were published by January 8, 2021, and the median time to publication was 48.0 months. Studies registered before this study began (HR = 1.69, 95% CI = 1.02–2.80, P = .040) and in phases 1/2 or 2 (HR = 2.10, 95% CI = 1.09–4.06, P = .026) were associated with an improved likelihood of publication. Conclusions OSCC clinical trials usually have small sample size and are open-label and non-randomized studies. Advanced OSCC and immunotherapy-oriented therapy are becoming the focus of current trials. Researchers should perform standardized registration and publish their results in a timely manner.
P. gingivalis is associated with a variety of systemic diseases and colonizes in distal locations in the body. Here, we found that P. gingivalis gingipains degrade PECAM-1 to promote bacterial penetration while simultaneously reducing leukocyte TEM capacity.
Aim As periodontitis and dyslipidemia are diseases that occur with high incidence, the relationship between them has attracted much attention. Previous studies on these diseases have tended to focus on lipid parameters and periodontitis, we aimed to investigate the relationship between dyslipidemia and periodontitis. Materials and Methods Studies were considered eligible if they contained data on abnormal blood lipid parameters and periodontitis. Studies that reported mean differences and 95% confidence intervals or odds ratios were used. Results 67 publications were included in the meta-analysis. Hyper total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels are risk factors for periodontitis. Periodontal disease is a risk factor for high TG and low HDL levels. Three months after periodontal treatment, the levels of TC, TG and HDL were significantly improved, and statin treatment only improved gingival index (GI) levels compared to that of the dietary control. Conclusions The findings reported here suggest that the mutual promotion of periodontitis and dyslipidemia can be confirmed. Non-surgical periodontal therapy may improve lipid abnormalities. It can’t be demonstrated whether systematic application of statins have a better effect on the improvement in periodontal status in patients with dyslipidemia compared to that of the control.
Aim: The regulation of osteoclasts (OCs) by inhibitory immunoreceptors maintains bone homeostasis and is considered an important determinant of the extent of periodontal pathology. The aim of this study was to investigate the role of the inhibitory immunoreceptor CD300lf and its ligand ceramide in osteoclastogenesis in periodontitis. Materials and Methods: The expression of CD300lf was measured in vitro and in a ligature-induced periodontitis model. The effect of CD300lf ablation on osteoclastogenesis was examined in ligature-retained and ligature removal periodontitis models. The effect of ceramide, the ligand of CD300lf, was examined in osteoclastogenesis in vitro and in vivo by smearing 20 μg of ceramide dissolved in carboxymethylcellulose on teeth and gingiva every other day in an experimental periodontitis model and ligature removal model. Results: CD300lf expression was downregulated during osteoclastogenesis. Ablation of CD300lf in the ligature-induced periodontitis model increased the number of OCs and exacerbated bone damage. Bone resorption caused by CD300lf ablation was reversible following ligature removal. CD300lf-ceramide binding suppressed osteoclastogenesis in vitro and inhibited alveolar bone loss in a mouse periodontitis model. Conclusions: Our findings reveal that CD300lf-ceramide binding plays a critical negative role in alveolar bone loss in periodontitis by inhibiting OCs differentiation.
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