Identification of novel genome-wide pleiotropic associations with oral inflammatory traits.

Oral inflammatory diseases (OIDs) are a group of dental diseases with multiple clinical manifestations that impact the majority of the world's population. Many studies have investigated the associations between individual OID traits and genomic variants, but whether pleiotropic loci are shared by oral inflammatory traits remains poorly understood. Here, we conducted multitrait joint analyses based on the summary statistics of genome-wide association studies (GWASs) of five dental traits from the UK Biobank. Among these genome-wide significant loci, two were novel for both painful gums and toothache. We identified causal variants at each novel locus, and functional annotation based on multiomics data suggested IL10 and IL12A/TRIM59 as potential candidate genes at the novel pleiotropic loci. Subsequent analyses of pathway enrichment and protein-protein interaction networks suggested the involvement of the candidate genes in immune regulation. In conclusion, our results uncover novel pleiotropic loci for OID traits and highlight the importance of immune regulation in the pathogenesis of OIDs. These findings will enhance our understanding of the pathogenesis of OIDs and be beneficial for risk screening, prevention, and the development of novel drugs targeting the immune regulation of OIDs.

Transformation of Feature Selectivity From Membrane Potential to Spikes in the Mouse Superior Colliculus.

Neurons in the visual system display varying degrees of selectivity for stimulus features such as orientation and direction. Such feature selectivity is generated and processed by intricate circuit and synaptic mechanisms. A key factor in this process is the input-output transformation from membrane potential (Vm) to spikes in individual neurons. Here, we use in vivo whole-cell recording to study Vm-to-spike transformation of visual feature selectivity in the superficial neurons of the mouse superior colliculus (SC). As expected from the spike threshold effect, direction and orientation selectivity increase from Vm to spike responses. The degree of this increase is highly variable, and interestingly, it is correlated with the receptive field size of the recorded neurons. We find that the relationships between Vm and spike rate and between Vm dynamics and spike initiation are also correlated with receptive field size, which likely contribute to the observed input-output transformation of feature selectivity. Together, our findings provide useful information for understanding information processing and visual transformation in the mouse SC.

Retinal origin of direction selectivity in the superior colliculus.

Detecting visual features in the environment, such as motion direction, is crucial for survival. The circuit mechanisms that give rise to direction selectivity in a major visual center, the superior colliculus (SC), are entirely unknown. We optogenetically isolate the retinal inputs that individual direction-selective SC neurons receive and find that they are already selective as a result of precisely converging inputs from similarly tuned retinal ganglion cells. The direction-selective retinal input is linearly amplified by intracollicular circuits without changing its preferred direction or level of selectivity. Finally, using two-photon calcium imaging, we show that SC direction selectivity is dramatically reduced in transgenic mice that have decreased retinal selectivity. Together, our studies demonstrate a retinal origin of direction selectivity in the SC and reveal a central visual deficit as a consequence of altered feature selectivity in the retina.

La(3+) Alters the Response Properties of Neurons in the Mouse Primary Somatosensory Cortex to Low-Temperature Noxious Stimulation of the Dental Pulp.

Although dental pain is a serious health issue with high incidence among the human population, its cellular and molecular mechanisms are still unclear. Transient receptor potential (TRP) channels are assumed to be involved in the generation of dental pain. However, most of the studies were conducted with molecular biological or histological methods. In vivo functional studies on the role of TRP channels in the mechanisms of dental pain are lacking. This study uses in vivo cellular electrophysiological and neuropharmacological method to directly disclose the effect of LaCl3, a broad spectrum TRP channel blocker, on the response properties of neurons in the mouse primary somatosensory cortex to low-temperature noxious stimulation of the dental pulp. It was found that LaCl3 suppresses the high-firing-rate responses of all nociceptive neurons to noxious low-temperature stimulation and also inhibits the spontaneous activities in some nonnociceptive neurons. The effect of LaCl3 is reversible. Furthermore, this effect is persistent and stable unless LaCl3 is washed out. Washout of LaCl3 quickly revitalized the responsiveness of neurons to low-temperature noxious stimulation. This study adds direct evidence for the hypothesis that TRP channels are involved in the generation of dental pain and sensation. Blockade of TRP channels may provide a novel therapeutic treatment for dental pain.

Derivation and growth characteristics of dental pulp stem cells from patients of different ages.

The dental pulp contains a relatively low number of stem cells; however, it is considered to be a promising source of stem cells for use in regenerative therapy. To date, it has remained elusive whether there are certain differences in the dental pulp stem cells (DPSCs) from donors of different ages. In the present study, DPSC lines were derived using teeth from children, adolescents, adults and aged donors. The derivation efficiency, the proliferative and apoptotic rate, cell marker expression and the differentiation capacity were investigated and compared among these DPSC lines. The derivation efficacy was decreased with increasing donor age. Although a large part of cell surface markers was expressed in all DPSC lines, the expression of CD29 was downregulated in the DPSCs from aged teeth. In addition, the doubling time of DPSCs from aged teeth was prolonged and the number of apoptotic cells was increased with the propagation. These DPSCs were able to differentiate into a neuronal linage, which positively expressed the neuron-specific class III beta-tubulin and microtubule­associated protein 2, as well as into an osteogenic lineage, which positively expressed CD45; however, these DPSCs from aged teeth were completely or partially deprived of differentiation capacity. By contrast, DPSCs from younger teeth displayed significantly higher vitality and a higher potential for use in dental regenerative medicine.

Biomechanical evaluation of maxillary Lefort Ι fracture with bioabsorbable osteosynthesis internal fixation.

The aim of this study was to apply biomechanical analysis model to evaluate the effects of bioabsorbable internal fixation devices on maxillary Lefort Ι fracture. CT scan technology and the finite element software (ansys) were used to establish three-dimensional finite element models of five resorbable internal fixation devices in maxillary Lefort Ι fractures. We used the model to calculate the stress of the upper jaw and internal fixation. We further analyzed the stability of fixation under four occlusions. The fixation using two bioabsorbable plates was not stable. The zygomaticomaxillary pillars fixation is more stable than other fixations. The stability of fracture fixation was influenced with the molar occlusion. The current study developed a functional three-dimensional finite element model of bioabsorbable internal fixation and compared the stability of five fixation methods for maxillary Lefort Ι fractures. The results would facilitate the application of bioabsorbable materials in dental clinic.

Functional protection of learning and memory abilities in rats with vascular dementia.

PURPOSE: The present study clarified the effects of repetitive transcranial magnetic stimulation (rTMS) in rats with vascular dementia (VaD) and explored the underlying mechanisms. METHODS: Two-vessel occlusion was used as a VaD model. Two weeks after carotid artery occlusion, high (5 Hz) or low (1 Hz) frequency rTMS were applied for 10 days. Spatial learning and memory abilities were tested with a Morris water maze. Hippocampal CA1 neurons were histologically examined. The expressions of mammalian target of rapamycin (mTOR) and eukaryotic initiation factor 4E (eIF-4E) in CA1 were detected by western blot, and immunohistochemistry. RESULTS: Unlike unlesioned control animals, VaD rats had an impaired morphology of CA1 neurons and a reduced ability of spatial memory. rTMS significantly improved both, the morphology and the learning and memory abilities of VaD rats compared to untreated lesioned rats. Protein expressions of mTOR and eIF-4E in CA1 of VaD rats were lower than in control rats but rTMS significantly increased the expression compared to untreated VaD rats. CONCLUSIONS: rTMS promotes recovery of learning and memory abilities of VaD rats. Molecular analysis suggests that the beneficial effect of rTMS may be partly induced by upregulation of protein expressions of mTOR and eIF-4E in CA1.

[Clinical features and therapy of benign lymphoepithelial lesion].

OBJECTIVE: To report the clinical features of benign lymphoepithelial lesion and to further characterize recommendations for its therapy strategy. METHODS: It was a retrospective case sires. Retrospective analyze the clinical characteristics, imaging features, pathological manifestation and the treatment effect from the clinical materials of 9 cases of patients with benign lymphoepithelial lesion presenting to Tianjin Eye Hospital from Jan 2006 to Dec 2007. RESULTS: The 9 cases, in which 7 cases were female, 7 cases had lesions on both eyes, demonstrated unpainful swelling of the lacrimal glands and in different degree of salivary glands or had history of tumor resection of salivary glands. Orbital CT scanning showed increased homogeneous density with clear boundary in the lacrimal gland area. Color doppler ultrasonography displayed elliptical space occupying with clear boundary and homogeneous internal echos of the lacrimal gland area. Six patients received treatment with large dose of glucocorticoid for 1 - 2 courses, and the symptoms and signs were significantly alleviated. Three patients were operated to excise the lacrimal gland masses due to imperfect treatment effect of medication or in order to make definite diagnosis. The postoperative pathological results supported the diagnosis of benign lymphoepithelial lesion. No recurrence happened in the follow-up. CONCLUSIONS: A clinical condition with swelling of either or both lacrimal gland and of any salivary gland, and accompanied with systemic relative diseases should be considered benign lymphoepithelial lesion. Imaging examinations are helpful to definite diagnosis. Most patients are sensitive to the glucocorticoid treatment. The dose of glucocorticoid should be large at the beginning of treatment. Surgical excision can be applied to the cases insensitive to medications or difficult to be diagnosed. The definite diagnosis should be made through pathological examinations.