Activation of aryl hydrocarbon receptor (AhR) alleviates depressive-like behaviors in LPS-induced mice.

The role of the aryl hydrocarbon receptor (AhR) in regulating oxidative stress and immune responses has been increasingly recognized. However, its involvement in depression and the underlying mechanisms remain poorly understood. This study aimed to investigate the effect of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous AhR ligand, on a lipopolysaccharide (LPS)-induced depression model and the underlying mechanism. After being treated with FICZ (50 mg/kg), male C57BL/6J mice received intraperitoneal injection of LPS and underwent behavioral tests 24 h later. The levels of inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, were measured in the hippocampus and serum using enzyme-linked immunosorbent assay (ELISA). The expression levels of CYP1A1, AhR and NLRP3 were analyzed using qPCR and Western blot. The results showed that, compared with control group, LPS alone significantly down-regulated the expression levels of CYP1A1 mRNA and AhR protein in the hippocampus of mice, reduced glucose preference, prolonged immobility time in forced swimming test, increased IL-6 and IL-1ß levels in the hippocampus, increased serum IL-1ß level, and up-regulated NLRP3 mRNA and protein expression levels in mouse hippocampus, while FICZ significantly reversed the aforementioned effects of LPS. These findings suggest that AhR activation attenuates the inflammatory response associated with depression and modulates the expression of NLRP3. The present study provides novel insights into the role of AhR in the development of depression, and presents AhR as a potential therapeutic target for the treatment of depression.

The involvement of NLRP3 inflammasome in CUMS-induced AD-like pathological changes and related cognitive decline in mice.

BACKGROUND: Numerous studies have found that inhibiting the expression of NLRP3 inflammasome can significantly improve depressive-like behaviors in mice, but the research on its effect on cognitive decline in depression and its mechanism is still lacking. This study aimed to elucidate the role of NLRP3 inflammasome in cognitive decline in depression and explore the common neuro-immunological mechanisms of depression and Alzheimer's disease (AD). METHODS: Male C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS) for 5 weeks, treatment group was administered with the NLRP3 inhibitor MCC950 (10 mg/kg, i.p.), fluoxetine served as positive control. Then, the mice were assessed for cognitive behaviors and depression-like behaviors, and changes of microglia and neurons in hippocampus and levels of Aß metabolic pathway and tau protein were measured. To explore the mechanism of NLRP3 activation on neurons, we performed in vitro studies using BV2 microglia and mouse primary neurons. Furthermore, we focused on the role of NLRP3 inflammasome in the function of neurons and the expression of AD pathological indicators. RESULTS: CUMS induced depressive-like behaviors and cognitive decline in mice, which could be reversed by inhibiting NLRP3 inflammasome. MCC950, a specific NLRP3 inhibitor, alleviated CUMS-induced neuron injury and AD-like pathological changes, including the abnormal expression of Aß metabolic pathway and the hyper-phosphorylation of tau protein. LPS (1 µg/mL) + ATP (1 mM) treatment activated the expression of NLRP3 inflammasome and IL-1ß in vitro. In vitro experiment also proved that inhibiting the expression of NLRP3 inflammasome in microglia can restore the Aß metabolic pathway to normal, decrease neuronal tau protein phosphorylation and protect neurons. CONCLUSIONS: Inhibition of NLRP3 inflammasome effectively alleviated CUMS-induced depressive-like behaviors and cognitive decline in mice, and inhibited the activation of AD physiological indicators.

Tooth ultrastructure changes induced by a nonsense mutation in the FAM83H gene: insights into the diversity of amelogenesis imperfecta.

OBJECTIVES: The current research on single-nucleotide polymorphism (SNP) mutation sites at different positions of the FAM83H gene and their phenotypic changes leading to amelogenesis imperfecta (AI) is inconsistent. We identified a previously reported heterozygous nonsense mutation c.1192C>T (p.Q398*) in the FAM83H gene and conducted a comprehensive analysis of the dental ultrastructure and chemical composition changes induced by this mutation. Additionally, we predicted the protein feature affected by this mutation site. The aim was to further deepen our understanding of the diversity of AI caused by different mutation sites in the FAM83H gene. METHODS: Whole-exome sequencing (WES) and Sanger sequencing were used to confirm the mutation sites. Physical features of the patient's teeth were investigated using various methods including cone beam computer tomography (CBCT), scanning electron microscopy (SEM), contact profilometry (roughness measurement), and a nanomechanical tester (nanoindentation measurement). The protein features of wild-type and mutant FAM83H were predicted using bioinformatics methods. RESULTS: One previously discovered FAM83H heterozygous nonsense mutation c.1192C>T (p.Q398*) was detected in the patient. SEM revealed inconsistent dentinal tubules, and EDS showed that calcium and phosphorus were lower in the patient's dentin but higher in the enamel compared to the control tooth. Roughness measurements showed that AI patients' teeth had rougher occlusal surfaces than those of the control tooth. Nanoindentation measurements showed that the enamel and dentin hardness values of the AI patients' teeth were both significantly reduced compared to those of the control tooth. Compared to the wild-type FAM83H protein, the mutant FAM83H protein shows alterations in stability, hydrophobicity, secondary structure, and tertiary structure. These changes could underlie functional differences and AI phenotype variations caused by this mutation site. CONCLUSIONS: This study expands the understanding of the effects of FAM83H mutations on tooth structure. CLINICAL RELEVANCE: Our study enhances our understanding of the genetic basis of AI and may contribute to improved diagnostics and personalized treatment strategies for patients with FAM83H-related AI.

Evaluation of the Efficacy of Stem Cells Therapy in the Periodontal Regeneration: A Meta-Analysis and Mendelian Randomization Study.

Stem cell therapy for periodontal defects has shown good promise in preclinical studies. The purpose of this study was to evaluate the impact of stem cell support on the regeneration of both soft and hard tissues in periodontal treatment. PubMed, Cochrane Library, Embase, and Web of Science were searched and patients with periodontal defects who received stem cell therapy were included in this study. The quality of the included articles was assessed using Cochrane's tool for evaluating bias, and heterogeneity was analyzed using the I2 method. An Mendelian randomization investigation was conducted using abstract data from the IEU public databases obtained through GWAS. Nine articles were included for the meta-analysis. Stem cell therapy effectively rebuilds periodontal tissues in patients with periodontal defects, as evidenced by a reduction in probing depth, clinical attachment level  and bone defect depth . And delta-like homolog 1 is a protective factor against periodontal defects alternative indicator of tooth loosening. The findings of this research endorse the utilization of stem cell treatment for repairing periodontal defects in individuals suffering from periodontitis. It is recommended that additional extensive clinical investigations be carried out to validate the efficacy of stem cell therapy and encourage its widespread adoption.

Type 1 diabetes, glycemic traits, and risk of dental caries: a Mendelian randomization study.

Background: Regarding past epidemiological studies, there has been disagreement over whether type 1 diabetes (T1DM) is one of the risk factors for dental caries. The purpose of this study was to determine the causative links between genetic susceptibility to T1DM, glycemic traits, and the risk of dental caries using Mendelian randomization (MR) approaches. Methods: Summary-level data were collected on genome-wide association studies (GWAS) of T1DM, fasting glucose (FG), glycated hemoglobin (HbA1c), fasting insulin (FI), and dental caries. MR was performed using the inverse-variance weighting (IVW) method, and sensitivity analyses were conducted using the MR-Egger method, weighted median, weighted mode, replication cohort, and multivariable MR conditioning on potential mediators. Results: The risk of dental caries increased as a result of genetic susceptibility to T1DM [odds ratio (OR) = 1.044; 95% confidence interval (CI) = 1.015-1.074; p = 0.003], with consistent findings in the replication cohort. The relationship between T1DM and dental caries was stable when adjusted for BMI, smoking, alcohol intake, and type 2 diabetes (T2DM) in multivariable MR. However, no significant correlations between the risk of dental caries and FG, HbA1c, or FI were found. Conclusion: These results indicate that T1DM has causal involvement in the genesis of dental caries. Therefore, periodic reinforcement of oral hygiene instructions must be added to the management and early multidisciplinary intervention of T1DM patients, especially among adolescents and teenagers, who are more susceptible to T1DM.

Evaluation of Hand Tendon Movement by Using High-Frequency Ultrasound Vector Doppler Imaging.

OBJECTIVE: Injuries to the hands, wrists, and fingers often involve damage to the tendons. The ability to measure tendon movements during the rehabilitation process can provide clinicians with important information in the quantification of tendon injuries. Conventionally, the tendon is considered a single spring-like structure during force transmission, and its twisted structure is neglected. Recently, clinicians believed that the twisted fiber structure (which enables tendon rotation during movement) of the tendon can provide it with a degree of elasticity and improve the efficiency of force transmission. However, observation of the hand tendon rotation in vivo by using the current imaging modalities is difficult. METHODS: In this study, a 40-MHz high-frequency vector Doppler imaging (HFVDI) was used to visualize the movement of the hand tendon during muscle contraction. The performance of HFVDI was verified using a rotation phantom experiment. Two human experiments were designed in the present study: 1) participants were allowed to bend their distal and proximal interphalangeal (DIP and PIP) joints of fingers freely and 2) the PIP joint of the finger was fixed such that only the DIP could be moved. The HFVDIs of the flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) tendons were obtained in the transverse and longitudinal views to observe the movements of the hand tendon during finger movements. RESULTS: The average longitudinal displacements of the FDS and FDP were approximately 3-4 mm for free bending of the finger; however, it was reduced when only the DIP was moved. The rotational phenomenon of the FDS and FDP tendons was observed in the transverse view, which demonstrated the different rotational behaviors of the FDS and FDP fibers during muscle contraction. CONCLUSION: All the results validated the potential of HFVDI as a novel tool for visualizing tendon rotation and would be useful in providing quantitative information regarding tendon function to determine the rehabilitation process following injuries.