Integrative multi-omics analysis identifies genetically supported druggable targets and immune cell specificity for myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating muscle weakness. Despite the availability of established therapies, the management of MG symptoms remains suboptimal, partially attributed to lack of efficacy or intolerable side-effects. Therefore, new effective drugs are warranted for treatment of MG. METHODS: By employing an analytical framework that combines Mendelian randomization (MR) and colocalization analysis, we estimate the causal effects of blood druggable expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) on the susceptibility of MG. We subsequently investigated whether potential genetic effects exhibit cell-type specificity by utilizing genetic colocalization analysis to assess the interplay between immune-cell-specific eQTLs and MG risk. RESULTS: We identified significant MR results for four genes (CDC42BPB, CD226, PRSS36, and TNFSF12) using cis-eQTL genetic instruments and three proteins (CTSH, PRSS8, and CPN2) using cis-pQTL genetic instruments. Six of these loci demonstrated evidence of colocalization with MG susceptibility (posterior probability > 0.80). We next undertook genetic colocalization to investigate cell-type-specific effects at these loci. Notably, we identified robust evidence of colocalization, with a posterior probability of 0.854, linking CTSH expression in TH2 cells and MG risk. CONCLUSIONS: This study provides crucial insights into the genetic and molecular factors associated with MG susceptibility, singling out CTSH as a potential candidate for in-depth investigation and clinical consideration. It additionally sheds light on the immune-cell regulatory mechanisms related to the disease. However, further research is imperative to validate these targets and evaluate their feasibility for drug development.

Systemic and Local Administration of a Dual-siRNA Complex Efficiently Inhibits Tumor Growth and Bone Invasion in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) accounts for nearly 90% of oral and oropharyngeal cancer cases and is characterized by high mortality and poor prognosis. RNA-based gene therapies have been developed as an emerging option for cancer treatment, but it has not been widely explored in OSCC. In this work, we developed an efficient siRNA cationic micelle DOTAP-mPEG-PCL (DMP) by self-assembling the cationic lipid DOTAP and monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) polymer. We tested the characteristics and transformation efficiency of this micelle and combined DMP with siRNA targeting STAT3 and TGF-ß to evaluate the antitumor effect and bone invasion interfering in vitro and in vivo. The average size of the DMP was 28.27 ± 1.62 nm with an average zeta potential of 54.60 ± 0.29 mV. The DMP/siRNA complex showed high delivery efficiency, with rates of 97.47 ± 0.42% for HSC-3. In vitro, the DMP/siSTAT3 complex exhibited an obvious cell growth inhibition effect detected by MTT assay (an average cell viability of 25.1%) and clonogenic assay (an average inhibition rate of 51.9%). Besides, the supernatant from HSC-3 transfected by DMP/siTGF-ß complexes was found to interfere with osteoclast differentiation in vitro. Irrespective of local or systemic administration, DMP/siSTAT3+siTGF-ß showed antitumor effects and bone invasion inhibition in the OSCC mice mandibular invasion model according to tumor volume assays and Micro-CT scanning. The complex constructed by DMP cationic micelles and siSTAT3+siTGF-ß represents a potential RNA-based gene therapy delivery system for OSCC.

Advances in periodontal stem cells and the regulating niche: From in vitro to in vivo.

Periodontium possesses stem cell populations for its self-maintenance and regeneration, and has been proved to be an optimal stem cell source for tissue engineering. In vitro studies have shown that stem cells can be isolated from periodontal ligament, alveolar bone marrow and gingiva. In recent years, more studies have focused on identification of periodontal stem cells in vivo. Multiple genetic markers, including Gli1, Prx1, Axin2, αSMA, and LepR, were identified with the lineage tracing approaches. Characteristics, functions, and regulatory mechanisms of specific populations expressing one of these markers have been investigated. In vivo studies also revealed that periodontal stem cells can be regulafrted by different niche and mechanisms including intercellular interactions, ECM and multiple secreted factors. In this review, we summarized the current knowledge of in vitro characteristics and in vivo markers of periodontal stem cells, and discussed the specific regulating niche.

Does Medullary Versus Cortical Invasion of the Mandible Affect Prognosis in Patients With Oral Squamous Cell Carcinoma?

PURPOSE: Whether mandibular involvement by oral squamous cell carcinoma (OSCC) could be identified as a factor for cancer staging and prognosis prediction remains a subject of debate. In addition, the influence of different types of mandibular invasion (cortical or medullary invasion) on patients' prognosis remains unclear. The aim of this systematic review was to establish whether mandibular invasion or its subset should be considered an independent prognostic factor for patients with OSCC. MATERIALS AND METHODS: The search for eligible studies was performed according to the predesigned inclusion criteria for a systematic review. Mandibular invasion and invasion depth were considered the primary and secondary predictor variables, respectively. The electronic search was performed using 12 databases. Manual searching covered 14 related journals and references of the included studies were scanned. The risk of bias assessment was evaluated by 2 reviewers using risk-of-bias assessment tools recommended by Saltaji et al (Angle Orthod 82:1115, 2012). Two reviewers extracted the data in duplicate. RevMan 5.2 was used for meta-analysis to assess the primary outcomes (disease-free survival and overall survival) and the secondary outcomes (2- and 5-year survival rate and local control). RESULTS: Eighteen studies (total, 3,756 participants) were included and used as the study sample. Among these included studies, 7 had an unclear risk of bias and the remaining showed a high risk. The results of the meta-analyses showed a significant relation between mandibular invasion and overall survival (P = .04) and, most importantly, that medullary involvement (P = .0001), but not cortical involvement (P = .66), could decrease overall survival. When focusing on disease-specific survival, mandibular medullary involvement predicted a poor disease-specific survival (P < .0001), but cortical involvement showed no effect (P = .66). CONCLUSION: This review showed that OSCC mandibular medullary invasion, and not mandibular invasion or mandibular cortical invasion, could be an independent prognostic factor for patients.

Emission Computed Tomography for the Diagnosis of Mandibular Invasion by Head and Neck Cancers: A Systematic Review and Meta-Analysis.

PURPOSE: To detect the diagnostic efficacy of emission computed tomography (ECT) in detecting mandibular invasion caused by head and neck cancers. MATERIALS AND METHODS: Thirteen databases were searched electronically to retrieve studies for inclusion and a manual search also was conducted. Study inclusion, data extraction, and quality assessment were completed by 2 reviewers independently. Meta-DiSc 1.4 and STATA 11.0 were used to conduct the meta-analysis. RESULTS: Seventeen studies involving 668 participants were included. One study had a low risk of bias, 2 had a high risk, and the rest had unclear risk. Meta-analysis showed that for the diagnosis of mandibular invasion single-photon ECT (SPECT) had a mean sensitivity (SEN) of 0.96, a mean specificity (SPE) of 0.66, an area under the curve (AUC) of 0.8989, and a Q* (point on the summary reviewer operator characteristic curve when SEN equaled SPE) of 0.8300. Positron emission tomography combined with computed tomography (PET/CT) had a mean SEN of 0.83, a mean SPE of 0.90, an AUC of 0.9290, and a Q* of 0.8640. The comparison between the diagnostic efficacy of SPECT and PET/CT showed that SPECT was superior for SEN (P = .0014) and PET/CT had a significantly better SPE (P = .001). The summary diagnostic efficacy between these modalities did not differ significantly (P > .05). CONCLUSIONS: The present clinical evidence showed that SPECT is an excellent tool to exclude patients with no mandibular invasion, but is not as good as PET/CT to confirm the diagnosis.

[Head and Neck Tumor Segmentation Based on Augmented Gradient Level Set Method].

To realize the accurate positioning and quantitative volume measurement of tumor in head and neck tumor CT images, we proposed a level set method based on augmented gradient. With the introduction of gradient information in the edge indicator function, our proposed level set model is adaptive to different intensity variation, and achieves accurate tumor segmentation. The segmentation result has been used to calculate tumor volume. In large volume tumor segmentation, the proposed level set method can reduce manual intervention and enhance the segmentation accuracy. Tumor volume calculation results are close to the gold standard. From the experiment results, the augmented gradient based level set method has achieved accurate head and neck tumor segmentation. It can provide useful information to computer aided diagnosis.

Computed tomography for the diagnosis of mandibular invasion caused by head and neck cancer: a systematic review comparing contrast-enhanced and plain computed tomography.

PURPOSE: To detect the diagnostic efficacy of computed tomography (CT) in distinguishing mandibular invasion caused by head and neck cancer and to compare the accuracy of contrast-enhanced and plain CT in the diagnosis. MATERIALS AND METHODS: Studies designed as cohort studies that detected the diagnostic efficacy of CT on mandibular invasion (including bone cortex and bone marrow invasion) and mandibular medullary alone (bone marrow invasion) were included. The included studies were required to use the pathologic diagnosis as the reference standard and reported true-positive, false-positive, false-negative, true-positive, and related data. Thirteen databases were electronically and manually searched to retrieve any possible related studies. Two reviewers independently conducted the study inclusion, data extraction, and assessment of the quality of the included studies. Meta-diSc, version 1.4, and STATA, version 11.0, were used to conduct the meta-analysis. RESULTS: A total of 30 studies with 1459 patients were included in the present study. Of those patients, 1,257 underwent CT and were accounted for in the meta-analysis. Of the included studies, 1 had a low risk and 6 had a high risk of bias; 23 studies had an unclear risk of bias. Meta-regression showed that the slight clinical heterogeneity did not influence the outcome (P > .10). The meta-analysis showed that CT for the diagnosis of mandibular invasion had a pooled sensitivity of 0.72, specificity of 0.90, positive likelihood ratio (+LR) of 5.33, negative likelihood ratio (-LR) of 0.36, diagnostic odds ratio (DOR) of 21.41, area under the curve (AUC) of 0.9022, and Q* (the value of the sensitivity or specificity when the sensitivity equals the specificity on the summary receiver operating characteristics curve) of 0.8336. The CT findings for mandibular medullar invasion had a sensitivity of 0.81, specificity of 0.85, +LR of 4.76, -LR of 0.24, DOR of 29.49, AUC of 0.9240, and Q* of 0.8580. No statistical significance was found in the sensitivity (P = .809), specificity (P = .27), AUC (P = .4296), and Q* (P = .4277) between the contrast-enhanced and plain CT scans. CONCLUSIONS: The present clinical evidence has shown that CT had an acceptable diagnostic value in detecting mandibular invasion caused by head and neck cancer. The high specificity of CT predicted it would be helpful when it was used to confirm the clinical diagnosis of bone invasion. Contrast-enhanced and plain CT scans had a similar diagnostic efficacy.

Significant enhancement of swallowing function and oral hygiene following multidisciplinary team nursing in tongue cancer patients after radical resection.

OBJECTIVE: To determine the effects of multidisciplinary team (MDT) nursing mode on the swallowing function and oral hygiene in patients after radical resection of tongue cancer (TC). METHODS: The data of 88 patients with TC treated in West China School/Hospital of Stomatology, Sichuan University were analyzed retrospectively. Among them, 42 patients who received routine nursing between February 2019 and February 2020 were assigned to a control group, and 46 patients who received MDT nursing between March 2020 and February 2022 were assigned to an observation group. The two groups were compared in the changes of postoperative swallowing function and oral hygiene, postoperative swallowing-related quality of life (QoL), and the survival rate for myocutaneous flap. The risk factors affecting swallowing function were analyzed through Logistic regression. RESULTS: After one month of nursing, the score of swallowing function decreased notably in both groups, with notably lower score in the observation group than that in the control group (P < 0.05). The control group exhibited notably lower oral cleanliness than the observation group after nursing (P < 0.05). Additionally, a notably lower survival rate of myocutaneous flap was found in the control group than that in the observation group (P < 0.05). The QoL scores of the two groups increased notably after nursing, and the observation group had notably higher QoL score than the control group (P < 0.05). The extent of glossectomy and nursing plan were independent risk factors impacting the recovery of swallowing function (P < 0.05). CONCLUSION: MDT nursing have a positive impact on oral hygiene as well as the swallowing function of patients after radical resection of TC, and MDT is a protective factor for swallowing function in the patients after radical resection.

Segmental mandibulectomy and microvascular reconstruction with fibula free flap: Comparison between intraoral and extraoral approaches.

BACKGROUND: Segmental mandibulectomy and reconstruction of resulting defect can be performed via intraoral approach (IOA) or extraoral approach (EOA). Both approaches have advantages, disadvantages, indications, and contraindications to consider during their selection. OBJECTIVE: To compare IOA vs EOA of segmental mandibulectomy and microvascular reconstruction with fibula free flap (FFF). METHODS: We conducted a retrospective cohort study in which 51 patients who underwent segmental mandibulectomy and microvascular reconstruction with FFF from 2020 to 2024 were included, especially 17 patients by IOA and 34 patients by EOA, representing both groups of this study. Clinical characteristics, surgery parameters, and patients' prognosis were evaluated. Patients' satisfaction and Derriford Appearance Scale (DAS59) were assessed during follow-up. RESULTS: Ameloblastoma was the most frequent diagnosis (52.9% managed by IOA vs 70.6% by EOA); FFF was frequently positioned as double barrel (94.1% managed by IOA vs 88.2% by EOA). Compared with EOA group, IOA group had less intraoperative blood loss (mean difference [MD] = -112.2, 95% confidence interval [CI]: -178.9 to -45.5, p = 0.001), higher satisfaction score (MD = 1.3, 95% CI: 0.9 to 1.7, p ˂ 0.001), and lower DAS59 score (MD = -0.5, 95% CI: -0.7 to -0.2, p ˂ 0.001). CONCLUSION: Both IOA and EOA were found safe and feasible, presenting similar perioperative features and postoperative outcomes. Patients managed with IOA were more satisfied with aesthetic outcomes than patients managed with EOA. In the absence of simultaneous immediate implant during mandibular FFF reconstruction, after stability of FFF on the defect site, patients should always be referred to an implantologist and/or prosthodontist for teeth restoration to improve functional and aesthetic outcomes.

Human papillomavirus infection and the risk of cancer at specific sites other than anogenital tract and oropharyngeal region: an umbrella review.

BACKGROUND: Despite numerous studies having evaluated the associations between human papillomavirus (HPV) infection and risk of specific cancers other than anogenital tract and oropharyngeal, the findings are inconsistent and the quality of evidence has not been systematically quantified. We aimed to summarise the existing evidence as well as to evaluate the strength and credibility of these associations. METHODS: We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, EMBASE, and Web of Science were searched from inception to March 2024. Studies with systematic reviews and meta-analyses that examined associations between HPV or HPV-associated genotypes infection and specific cancers were eligible for this review. The quality of the methodology was evaluated using A Measurement Tool to Assess systematic Reviews (AMSTAR). The credibility of the evidence was assessed using GRADE. The protocol was preregistered with PROSPERO (CRD42023439070). FINDINGS: The umbrella review identified 31 eligible studies reporting 87 associations with meta-analytic estimates, including 1191 individual studies with 336,195 participants. Of those, 29 (93.5%) studies were rated as over moderate quality by AMSTAR. Only one association indicating HPV-18 infection associated with an increased risk of breast cancer (odds ratio [OR] = 3.48, 95% confidence interval [CI] = 2.24-5.41) was graded as convincing evidence. There were five unique outcomes identified as highly suggestive evidence, including HPV infection increased the risk of oral squamous cell carcinoma (OR = 7.03, 95% CI = 3.87-12.76), oesophageal cancer (OR = 3.32, 95% CI = 2.54-4.34), oesophageal squamous cell carcinoma (OR = 2.69, 95% CI = 2.05-3.54), lung cancer (OR = 3.60, 95% CI = 2.59-5.01), and breast cancer (OR = 6.26, 95% CI = 4.35-9.00). According to GRADE, one association was classified as high, indicating that compared with the controls in normal tissues, HPV infection was associated with an increased risk of breast cancer. INTERPRETATION: The umbrella review synthesised up-to-date observational evidence on HPV infection with the risk of breast cancer, oral squamous cell carcinoma, oesophageal cancer, oesophageal squamous cell carcinoma, and lung cancer. Further larger prospective cohort studies are needed to verify the associations, providing public health recommendations for prevention of disease. FUNDING: National Key Research and Development Program of China, Natural Science Foundation of China, Outstanding Scientific Fund of Shengjing Hospital of China Medical University, and 345 Talent Project of Shengjing Hospital of China Medical University.

Mapping of individual sensory nerve axons from digits to spinal cord with the transparent embedding solvent system.

Achieving uniform optical resolution for a large tissue sample is a major challenge for deep imaging. For conventional tissue clearing methods, loss of resolution and quality in deep regions is inevitable due to limited transparency. Here we describe the Transparent Embedding Solvent System (TESOS) method, which combines tissue clearing, transparent embedding, sectioning and block-face imaging. We used TESOS to acquire volumetric images of uniform resolution for an adult mouse whole-body sample. The TESOS method is highly versatile and can be combined with different microscopy systems to achieve uniformly high resolution. With a light sheet microscope, we imaged the whole body of an adult mouse, including skin, at a uniform 0.8 × 0.8 × 3.5 µm3 voxel resolution within 120 h. With a confocal microscope and a 40×/1.3 numerical aperture objective, we achieved a uniform sub-micron resolution in the whole sample to reveal a complete projection of individual nerve axons within the central or peripheral nervous system. Furthermore, TESOS allowed the first mesoscale connectome mapping of individual sensory neuron axons spanning 5 cm from adult mouse digits to the spinal cord at a uniform sub-micron resolution.

Extraskeletal myxoid chondrosarcoma of the gingival: a rare case report and review of the literature.

BACKGROUND: Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant tumor described in the head and neck region, especially in the gingival. We present one case arising in the gingival of right mandible, and briefly reviewed the related literature. CASE PRESENTATION: A 24-year-old male patient with a lesion of 3.5*2.0 cm in buccal gingival of right posterior mandible for 2 months. The tumor was composed of cartilaginous structures and myxoid matrix. Immunohistochemical(IHC) showed that the tumor cells to be positive for vimentin, focally positive for S-100, negative for calponin, SMA, SOX10. The Ki-67 labelling index was 80%. Fluorescent in situ Hybridization (FISH) was positive for NR4A3 rearrangement. CONCLUSIONS: Due to its unusual site and low incidence in the oral region, a combination of histological findings, immunohistochemistry, and molecular pathology as well as differential diagnosis with other diseases should be taken into consideration in the process of clinical diagnosis and treatment.

Promotion effect of TGF-ß-Zfp423-ApoD pathway on lip sensory recovery after nerve sacrifice caused by nerve collateral compensation.

Resection of oral and maxillofacial tumors is often accompanied by the inferior alveolar nerve neurectomy, resulting in abnormal sensation in lower lip. It is generally believed that spontaneous sensory recovery in this nerve injury is difficult. However, during our follow-up, patients with inferior alveolar nerve sacrifice showed different degrees of lower lip sensory recovery. In this study, a prospective cohort study was conducted to demonstrate this phenomenon and analyze the factors influencing sensory recovery. A mental nerve transection model of Thy1-YFP mice and tissue clearing technique were used to explore possible mechanisms in this process. Gene silencing and overexpression experiments were then conducted to detect the changes in cell morphology and molecular markers. In our follow-up, 75% of patients with unilateral inferior alveolar nerve neurectomy had complete sensory recovery of the lower lip 12 months postoperatively. Patients with younger age, malignant tumors, and preservation of ipsilateral buccal and lingual nerves had a shorter recovery time. The buccal nerve collateral sprouting compensation was observed in the lower lip tissue of Thy1-YFP mice. ApoD was demonstrated to be involved in axon growth and peripheral nerve sensory recovery in the animal model. TGF-ß inhibited the expression of STAT3 and the transcription of ApoD in Schwann cells through Zfp423. Overall, after sacrificing the inferior alveolar nerve, the collateral compensation of the ipsilateral buccal nerve could innervate the sensation. And this process was regulated by TGF-ß-Zfp423-ApoD pathway.

Nursing Teaching Curriculum Setting by Introducing Postcompetency Model under the Vision of Internet Informatization.

The nursing curriculum is to be modernized to improve the student's skills in meeting the recent trends in medical and healthcare fields. The curriculum improvements are based on expert recommendations, authors, and informative data from different web sources. The challenging task is to improve the readability and understandability of the curriculum to real-time standards. Considering the above facts, this article introduces a refined curriculum with Internet information analysis (RC-IIA) method. The proposed method incorporates the distributed Internet, journal, and previous curriculum information within the active nursing syllabus. This prevents repetitions and less-informative content within the active curriculum. Besides, classification learning for knowledge-based representations is used within the curriculum to improve competency. Based on the refined information, a recommendation-based curriculum is preferred for varying information across different standards. The proposed analysis method relies on existing and distributed information across multiple curriculum providers for leveraging the visibility and prolonging the stealth of the nursing curriculum.

Local and Systemic Delivery of the BimS Gene Nano-Complex for Efficient Oral Squamous Cell Carcinoma Therapy.

Purpose: Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, with more than 300,000 new cases annually. Despite advances in existing treatments, including surgery, radiation, chemotherapy, and immunotherapy, the overall survival and prognosis have remained poor. However, gene therapy based on non-viral vectors provides new ideas for the treatment of OSCC. Here, we aimed to prepare and describe the synthesis, biosafety, and preclinical efficacy of DOTAP-mPEG-PCL (DMP) in OSCC gene therapy. Methods: We prepared a nano-sized hybrid cationic micelle DMP. DMP micelles were prepared by self-assembling cationic lipid DOTAP and mPEG-PCL polymer. We evaluated the characteristics of this cationic micelle in vitro. Combined with encoding the apoptosis-inducing BimS gene, we established the DMP/phBimS complex and evaluated its anti-tumor effect in vitro. We also established a mouse tongue xenograft model to evaluate the antitumor effect of the DMP/phBimS complex in vivo through local and systemic administration prospectively. Results: The DMP cationic micelle is spherical in shape, with an average diameter of 28.32 ± 3.56 nm and an average zeta potential of 43.43 ± 0.82 mV. By activation of lipid raft-mediated endocytosis caveolin-mediated endocytosis, DMP could efficiently deliver plasmid into SCC15 cells (efficiency: 52.07% ± 1.63%), with an ideal biosecurity. When loaded by plasmid encoding the apoptosis-inducing BimS gene, the DMP/phBimS complex exhibited an obvious anti-proliferation effect of SCC15 in vitro through the apoptosis pathway (33.9% ± 2.62% apoptosis rate). By local administration, the DMP/phBimS complex showed ideal anti-tumor properties in the nude mouse tongue xenograft model, with an average tumor inhibition rate of 65.66%. Furthermore, through systematic administration, the DMP/phBimS complex obviously inhibited OSCC growth, with an average inhibition rate of 45.63% (DMP/phBimS) and an appropriate biocompatibility. Conclusion: The DMP/phBimS complex is an optional effective option for suicide gene therapy for OSCC.

Response of Gli1+ Suture Stem Cells to Mechanical Force Upon Suture Expansion.

Normal development of craniofacial sutures is crucial for cranial and facial growth in all three dimensions. These sutures provide a unique niche for suture stem cells (SuSCs), which are indispensable for homeostasis, damage repair, as well as stress balance. Expansion appliances are now routinely used to treat underdevelopment of the skull and maxilla, stimulating the craniofacial sutures through distraction osteogenesis. However, various treatment challenges exist due to a lack of full understanding of the mechanism through which mechanical forces stimulate suture and bone remodeling. To address this issue, we first identified crucial steps in the cycle of suture and bone remodeling based on the established standard suture expansion model. Observed spatiotemporal morphological changes revealed that the remodeling cycle is approximately 3 to 4 weeks, with collagen restoration proceeding more rapidly. Next, we traced the fate of the Gli1+ SuSCs lineage upon application of tensile force in three dimensions. SuSCs were rapidly activated and greatly contributed to bone remodeling within 1 month. Furthermore, we confirmed the presence of Wnt activity within Gli1+ SuSCs based on the high co-expression ratio of Gli1+ cells and Axin2+ cells, which also indicated the homogeneity and heterogeneity of two cell groups. Because Wnt signaling in the sutures is highly upregulated upon tensile force loading, conditional knockout of ß-catenin largely restricted the activation of Gli1+ SuSCs and suppressed bone remodeling under physiological and expansion conditions. Thus, we concluded that Gli1+ SuSCs play essential roles in suture and bone remodeling stimulated by mechanical force and that Wnt signaling is crucial to this process. © 2022 American Society for Bone and Mineral Research (ASBMR).

Tissue Clearing and 3-D Visualization of Vasculature with the PEGASOS Method.

Tissue clearing techniques turn tissue transparent through a series of chemical and physical treatments. They have provided a useful tool for three-dimensional (3-D) imaging to study tissue spatial organization and interactions. Many tissue clearing methods have been developed in recent years. Each method has its own application range depending on the purposes of the study. Three criteria for selecting an appropriate clearing method include clearing transparency, fluorescence preservation, and broad tissue applicability. PEG-associated solvent system (PEGASOS) emerged recently as a solvent-based tissue clearing method capable of rendering diverse tissues highly transparent while preserving fluorescence. Combined with vascular labeling techniques, PEGASOS method enables 3-D visualization of vasculature in whole tissues at subcellular resolution. Here, we describe the standard PEGASOS passive immersion protocol and several compatible vascular labeling techniques. Methods of 3-D imaging, data processing, and annotations are also briefly introduced.

Dental-Derived Mesenchymal Stem Cells: State of the Art.

Mesenchymal stem cells (MSCs) could be identified in mammalian teeth. Currently, dental-derived MSCs (DMSCs) has become a collective term for all the MSCs isolated from dental pulp, periodontal ligament, dental follicle, apical papilla, and even gingiva. These DMSCs possess similar multipotent potential as bone marrow-derived MSCs, including differentiation into cells that have the characteristics of odontoblasts, cementoblasts, osteoblasts, chondrocytes, myocytes, epithelial cells, neural cells, hepatocytes, and adipocytes. Besides, DMSCs also have powerful immunomodulatory functions, which enable them to orchestrate the surrounding immune microenvironment. These properties enable DMSCs to have a promising approach in injury repair, tissue regeneration, and treatment of various diseases. This review outlines the most recent advances in DMSCs' functions and applications and enlightens how these advances are paving the path for DMSC-based therapies.

Application of platelet-rich fibrin on mandibular third molar extraction: systematic review and Meta-analysis.

OBJECTIVES: This study aims to analyze the effectiveness of platelet-rich fibrin (PRF) in mandibular third molar extraction and provide suggestions for alleviating postoperative complications. METHODS: Pubmed, EMBASE, Web of Science, and SinoMed were searched electronically on February 2020. Randomized controlled trials focusing on PRF usage in mandibular third molar extraction were included. Reviewers assessed the risk of bias in the included literature and extracted data independently using the criteria recommended by the Cochrane Collaboration. Meta-analysis was performed using RevMan 5.3 and STATA 13.0. RESULTS: Twenty-one studies were included, comprising 991 patients who had mandibular third molar extraction. The topical application of PRF effectively reduced pain after extraction [MD=-12.06, 95%CI (-21.42, -2.71), P=0.01], attenuated post-extraction swelling [MD=-1.42, 95%CI (-2.41, -0.44), P=0.005], and promoted soft tissue hea-ling [MD=0.66, 95%CI (0.34, 0.99), P<0.000 1]. PRF significantly reduced trismus and alveolar osteitis (P<0.05). However, data could not prove whether PRF has any significant positive effect on bone healing compared with the control group (P>0.05). CONCLUSIONS: Limited clinical evidence indicates that applying PRF after mandibular third molar extraction could reduce pain, swelling, trismus and the occurrence of dry socket and promote soft tissue healing. However, the effect of PRF on bone healing requires further large-scale randomized controlled trials and unified measurement criteria.

Smad7 attenuates TGF-ß-mediated aging-related hypofunction of submandibular glands.

Submandibular glands have essential functions in taste, mastication, swallowing, and digestion. Submandibular gland hypofunction is prevalent in the elderly, impairing the patients' quality of life. Current clinical treatment strategies have not decelerated or reversed the pathological process of submandibular gland hypofunction. Therefore, novel restoration strategies should be explored. However, studies on the mechanism of aging-related submandibular gland hypofunction remain very limited. The role of the TGF-ß/Smad pathway in fibrosis has been studied in other organs. Therefore, this study aimed to elucidate the role of TGF-ß/Smad signaling in the aging-related submandibular gland hypofunction. The results showed that Smad7 knockout in mice decreased the salivary flow rate. H&E, Masson trichrome, and immunohistochemistry staining of MCP-1 and α-SMA showed that Smad7 knockout in mice resulted in lymphocytic infiltration, acinar cell atrophy, and interstitial fibrosis. The Western blotting of collagen I and III also confirmed extensive fibrosis. We then found that Smad7 depletion resulted in the TGF-ß-mediated fibrosis via mir-21, mir-29, and np_5318, and NFκB-driven inflammation activation. This study confirmed the inhibitory role of Smad7 in the aging-related submandibular gland hypofunction. Therefore, it provided a promising treatment target for aging-related dysfunction and sialadenitis of submandibular gland.