The probability of suffering the mood disorder depression is up to 30% in women and 15% in men during their life span. Pharmacological options for depression are limited: conventional antidepressants have low efficacy and a delayed onset of action (several weeks). Here we investigate the antidepressant actions of inhibitors of monoacylglycerol lipase (MAGL), the major degradative enzyme of the endocannabinoid 2-arachidonoylglycerol. A low-dose of MAGL inhibitors produces antidepressant effects on acute stress-exposed mice, through glutamatergic synaptic long-term depression (LTD), without significant effects on chronic corticosterone-exposed mice. In contrast, a high-dose of MAGL inhibitors produces pro- or antidepressant effects on acute stress- or chronic corticosterone-exposed mice, respectively, through GABAergic synaptic disinhibition. In the hippocampus, in vivo inhibition of MAGL induces a CB₁ cannabinoid receptor (CB₁R)-dependent suppression of inhibitory GABAergic synapses and an in vivo LTD of excitatory glutamatergic synapses. LTD induction requires CB₁R in astroglial cells (but not in GABAergic or glutamatergic neurons) and postsynaptic glutamate receptors. The conventional antidepressant fluoxetine produces rapid or delayed antidepressant effects in acute stress- or chronic corticosterone-exposed mice, respectively. We propose that depression-like behavior of animals in response to acute stress is the normal behavioral response, and thus, MAGL inhibitors, which produce antidepressant effects in chronic corticosterone-exposed animals through GABAergic synaptic disinhibition, represent a new class of rapidly-acting and long-lasting antidepressants.

Objectives: To compare the correlation of depth of invasion (DOI) measured on multiple magnetic resonance imaging (MRI) sequences and pathological DOI, in order to determine the optimal MRI sequence for measurement. Methods: A total of 122 oral tongue squamous cell carcinoma (OTSCC) patients were retrospectively analyzed, who had received preoperative MRI and surgical resection. DOIs measured on fat-suppressed T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), dynamic enhanced-T1 high-resolution insotropic volume examination (e-THRIVE), and contrast-enhanced fat-suppressed T1WI (CE-T1WI) were respectively compared to those measured in pathologic specimens. The cutoff value of the best correlated MRI sequence was determined, and the T staging accuracy of MRI-derived DOI was evaluated. Results: DOI derived from e-THRIVE showed the best correlation (r = 0.936, p < 0.001) with pathological DOI. The area under the curve values of MRI-derived DOI distinguishing T1 stage from T2 stage and distinguishing T2 stage from T3 stage were 0.969 and 0.974, respectively. The T staging criteria of MRI-derived DOI were 6.2 mm and 11.4 mm, with a staging accuracy of 86.9% compared to pathological DOI criteria of 5 mm and 10 mm. Conclusion: E-THRIVE was the optimal MR sequence to measure the MR-derived DOI, and DOI derived from e-THRIVE could serve as a potential cut-off value as a clinical T staging indicator of OTSCC. Key Points: • Multiparametric MRI helps radiologists to assess the neoplasm invasion in patients with oral tongue squamous cell carcinoma. • Retrospective study indicated that measurement was most accurate on enhanced-T1 high-resolution insotropic volume examination dynamic contrast enhancement images. • T staging of oral tongue squamous cell carcinoma was accurate according to the dynamic contrast enhancement MRI-derived depth of invasion.

Background: Sleep apnea exerts adverse health effects due to inflammation and metabolic disruption. It is associated with metabolic diseases. However, the evidence of its relationship with depression is inconsistent. Therefore, this study aimed to investigate the relationship between sleep apnea and depressive symptoms in adults in the United States. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES), wherein the data from 2005 to 2018 of 9,817 individuals were obtained. Sleep apnea was self-reported by the participants using a questionnaire on sleep disorders. The 9-item Patient Health Questionnaire (PHQ-9) was used to assess depressive symptoms. We implemented multivariable logistic regression and stratified analyses to assess the correlation between sleep apnea and depressive symptoms. Results: A total of 515 (6.6%) participants among 7,853 non-sleep apnea participants and 269 (13.7%) subjects among 1,964 sleep apnea participants had a depression score ≥ 10, they were deemed to have depressive symptoms. The multivariable regression model, showed that individuals with sleep apnea were 1.36-fold more likely to experience depressive symptoms when adjusted for potential covariates (odds ratios [OR] with 95% confidence intervals of 2.36 [1.71–3.25]), and a positive correlation between depressive symptoms and sleep apnea severity was found. The stratified analyses, revealed that sleep apnea was related to an increased incidence of depressive symptoms in most subgroups, except for those with coronary heart disease. Further, there was no interaction between sleep apnea and the covariates. Conclusions: Adults with sleep apnea in the US have a relatively high prevalence of depressive symptoms. and the severity of sleep apnea positively correlated with the depressive symptoms.

Background: The activation of the unfolded protein response (UPR) has been demonstrated in periodontal diseases. However, the cellular and molecular mechanisms by which the UPR is induced in periodontitis remain unclear. In this study, the effects of lipopolysaccharide (LPS) on the induction of the UPR in human periodontal ligament fibroblasts (HPDLFs) in vitro are investigated.Methods: HPDLFs isolated from human PDLs were stimulated with various concentrations of Escherichia coli LPS (0.1, 1, and 10 μg/mL) for the indicated time points (0, 3, 6, 9, 12, and 18 hours). The messenger RNA (mRNA) and protein levels of molecular markers associated with UPR activation, such as glucose‐regulated protein 78 (GRP78), X‐box binding protein 1 (XBP1), and C/EBP homologous protein (CHOP), were measured at different time points of LPS treatment. Apoptosis of HPDLFs was assessed by Annexin V‐FITC and propidium iodide staining, followed by flow cytometry.Results: LPS treatment of HPDLFs increased GRP78 mRNA and protein levels in a concentration‐dependent manner. Additionally, LPS also induced the expression, splicing, and activation of XBP1 mRNA. Moreover, LPS‐induced CHOP expression was concentration dependent: a lower concentration of LPS (0.1 μg/mL) had no effect on CHOP mRNA levels, but higher concentrations of LPS (1 and 10 μg/mL) markedly increased CHOP mRNA and protein expression without inducing apoptosis.Conclusion: The findings demonstrate that activating the Toll‐like receptor‐4 signaling pathway in HPDLFs using LPS triggers the UPR in vitro, warranting additional investigation into the precise mechanisms by which pathways promote this response under inflammatory conditions.