Regulating the coordination environment of single atom catalysts anchored on C3N monolayer for Li-S battery by first-principles calculations.

Owing to the extremely high theoretical specific capacity and energy density, the catalytic materials of lithium-sulfur (Li-S) batteries are widely explored. The "shuttle effect", poor electrode conductivity, and slow charge-discharge reaction dynamics are some of the key issues that have seriously hampered their commercialization process. Herein, based on the density-functional-theory (DFT), the catalytic performances of a series of single-atom catalysts (SACs) designed by regulating the N-content around coordination center in C3N (TM@N2C2/N3C/N4-C3N (TM = Ti, V, Fe, Co, Ni)), are systematically analyzed and evaluated. Among all the constructed SACs, Ti-centered configurations with fewer d electrons, especially for the Ti@N2C2-C3N, have the remarkable catalytic effect in improving the electron conductivity, trapping soluble polysulfides and accelerating the redox reaction. The in-depth mechanism indicates that the interaction between d orbital of Ti, mainly the splitting [Formula: see text] , and p orbital of S is the key factor for achieving high-effective adsorption. More importantly, the integral value of crystal orbital Hamiltonian population (ICOHP) of the Li-S bond in the adsorbed Li2S can serve as an excellent descriptor for evaluating the overall catalytic ability of substrates. Our work has vital guiding significance for designing high-performance SACs of Li-S batteries.

Bredigite-Based Bioactive Nerve Guidance Conduit for Pro-Healing Macrophage Polarization and Peripheral Nerve Regeneration.

Structural and functional healing of peripheral nerves damaged by trauma or chronic disease remain major clinical challenges, requiring the development of an effective nerve guidance conduit (NGC). The present study investigates a NGC fabrication strategy based on bredigite (BRT, Ca7 MgSi4 O16 ) bioceramic for the treatment of peripheral nerve injury. Here, BRT bioceramic shows good biocompatibility and sustainable release of Ca2+ , Mg2+ , and Si4+ ions. Both BRT extracts and BRT-incorporating electrospun membranes promote the proliferation and myelination potential of RSC96 cells, as well as accelerate vascular formation by human umbilical vein endothelial cells. Notably, BRT facilitates RAW 264.7 cell polarization to the pro-healing phenotype under LPS-induced inflammatory stimulation. More importantly, the macrophages activated by BRT in turn promote RSC96 cell migration and remyelination. In a rat sciatic nerve defect model, improved electrophysiological performance and alleviated gastrocnemius muscle atrophy are observed at 12 weeks post-implantation. Further experiments verify that BRT-loaded NGC facilitates axonal regrowth and revascularization with high M2-like macrophage infiltration. These findings support the beneficial effects of BRT for creating a pro-healing immune microenvironment and orchestrating multicellular processes associated with functional nerve regeneration, indicating the potential of rationally engineered bioceramics as safe, effective, and economical materials for peripheral nerve repair.

Mucin 1 promotes salivary gland cancer cell proliferation and metastasis by regulating the epidermal growth factor receptor signaling pathway.

Background/purpose: Salivary gland cancer (SGC) is the common malignant tumor of the head and neck region with poor prognosis. Mucin 1 (MUC1) has been reported to be associated with the development of cancer. However, whether MUC1 contributed to the progression of SGC remains to be explored. Materials and methods: Immunohistochemical analysis was used to explore the expression levels of MUC1 in SGC tissues. Cell proliferation, colony formation, wound healing, transwell, and xenograft assays were performed to examine the effects of MUC1 on SGC in vitro and in vivo. Results: We found that the expression level of MUC1 was significantly upregulated in SGC tissues, and the expression level of MUC1 was significantly correlated with lymph node metastasis and TNM stage of SGC. Further exploration demonstrated that MUC1 knockdown drastically inhibited, while its overexpression promoted, cell growth, colony formation, migration, and invasion abilities of SGC cells in vitro. MUC1 knockdown significantly inhibited tumor growth in vivo, and vice versa. More importantly, we found that MUC1 promotes malignant phenotypes of SGC cells by regulating the epidermal growth factor receptor (EGFR) signaling pathway. Conclusion: Our results revealed that MUC1 promotes the development of SGC by mediating the EGFR signaling pathway, which highlights the potential therapeutic target of MUC1/ EGFR in SGC.

Li-Mg-Si bioceramics provide a dynamic immuno-modulatory and repair-supportive microenvironment for peripheral nerve regeneration.

Biomaterials can modulate the local immune and repair-supportive microenvironments to promote peripheral nerve regeneration. Inorganic bioceramics have been widely used for regulating tissue regeneration and local immune response. However, little is known on whether inorganic bioceramics can have potential for enhancing peripheral nerve regeneration and what are the mechanisms underlying their actions. Here, the inorganic lithium-magnesium-silicon (Li-Mg-Si, LMS) bioceramics containing scaffolds are fabricated and characterized. The LMS-containing scaffolds had no cytotoxicity against rat Schwann cells (SCs), but promoted their migration and differentiation towards a remyelination state by up-regulating the expression of neurotrophic factors in a ß-catenin-dependent manner. Furthermore, using single cell-sequencing, we showed that LMS-containing scaffolds promoted macrophage polarization towards the pro-regenerative M2-like cells, which subsequently facilitated the migration and differentiation of SCs. Moreover, implantation with the LMS-containing nerve guidance conduits (NGCs) increased the frequency of M2-like macrophage infiltration and enhanced nerve regeneration and motor functional recovery in a rat model of sciatic nerve injury. Collectively, these findings indicated that the inorganic LMS bioceramics offered a potential strategy for enhancing peripheral nerve regeneration by modulating the immune microenvironment and promoting SCs remyelination.

Clinicopathological characteristics of pleomorphic adenoma from the labial gland: A 20-year experience with 173 cases in one single institution.

OBJECTIVE: Pleomorphic adenoma (PA) of the lip is not a common phenomenon, and existing literature provides limited information on the clinicopathological features of labial PA. STUDY DESIGN: Patients diagnosed with labial PA at our single institution over the past 20 years (2001-2020) was retrospectively screened and analyzed to investigate the epidemiologic and clinicopathological features of these tumors. RESULTS: A total of 173 cases were screened out, and the average age was 44.3 (range 7-82) years, with a peak incidence rate during the third decade. A slight predilection for men (52%) was observed, and PA occurs more frequently in the upper lip than in the lower lip, with a ratio of 14.7:1. On clinical examination, labial PAs usually present as painless masses that develop slowly with no systemic symptoms. Histologically, labial PAs contain myoepithelial and polygonal epithelial cells in myxoid, hyaline, fibrous, chondroid, and even osseous tissues, similar to those in other sites. Specifically, 15 of 173 patients with labial PA presented with cutaneous PA. CONCLUSION: Labial PA presents over a wide age range and dominantly occurs at the upper lip. Surgical resection is the major treatment strategy, and postoperative recurrence or malignant transformation of labial PA was extremely rare.

Malignant sublingual gland tumors: A single-center retrospective analysis of 79 patients.

OBJECTIVES: To analyze and summarize the clinicopathological features, risk factors for cervical nodal metastasis, and prognostic factors of malignant sublingual gland tumors (MSLGT). METHODS: Patients diagnosed with MSLGT were retrospectively reviewed from January 2005 to December 2017 at Shanghai Ninth Hospital. The clinicopathological features were summarized, and the correlations between clinicopathological parameters, cervical nodal metastasis, and local-regional recurrence were evaluated using the Chi-square test. Kaplan-Meier method and Cox regression analysis were performed to assess the survival and independent prognostic factors. RESULTS: Seventy-nine patients were included, and the 5-year overall survival and disease-free survival rates was 85.7% and 71.7%, respectively. Gender and clinical tumor stage were risk factors for cervical nodal metastasis. Tumor size and pathological lymph node (LN) stage were independent prognostic factors for adenoid cystic carcinoma (ACC) of the sublingual gland; while age, pathological LN stage, and distant metastasis were prognostic factors for patients with non-ACC of the sublingual gland. Patients with higher clinical stage were more likely to undergo tumor recurrence. CONCLUSIONS: Malignant sublingual gland tumors are rare, and neck dissection should be performed in male MSLGT patients with higher clinical stage. Among patients with both ACC and non-ACC MSLGT patients, pN+ indicate a poor prognosis.

Injectable hydrogel encapsulated with VEGF-mimetic peptide-loaded nanoliposomes promotes peripheral nerve repair in vivo.

Repair of peripheral nerve crush injury remains a major clinical challenge. Currently, oral or intravenous neurotrophic drugs are the main treatment for peripheral nerve crush injury; however, this repair process is slow, and the final effect may be uncertain. The current study aimed at developing an injectable hydrogel with vascular endothelial growth factor (VEGF)-mimetic peptide (QK)-encapsulated nanoliposomes (QK-NLs@Gel) for sustainable drug release that creates an appropriate microenvironment for nerve regeneration. The QK-encapsulated nanoliposomes (QK-NLs) could facilitate the proliferation, migration, and tube formation capacities of human umbilical vein endothelial cells through the VEGF signaling pathway. The QK-NLs@Gel hydrogel encapsulated with QK-NLs showed enhanced physical properties and appropriate biocompatibility in vitro. Thereafter, the QK-NLs@Gel hydrogel was directly injected into the site of peripheral nerve crush injury in a rat model, where it enhanced revascularization and promoted the M2-polarization of the macrophages, thus providing an optimized microenvironment for nerve regeneration. At four weeks post-surgery, the QK-NLs@Gel injected rats exhibited enhanced axon regeneration, remyelination, and better functional recovery in comparison with other groups in vivo. Overall, these findings demonstrate that the composite hydrogel could promote a multicellular pro-regenerative microenvironment at the peripheral nerve injury site, thus revealing great potential for peripheral nerve restoration. STATEMENT OF SIGNIFICANCE: Peripheral nerve injury (PNI) is a leading public health issue, and how to delivery beneficial drugs to injured sites efficiently is still a big challenge. In the current study, an injectable hydrogel with VEGF-mimetic peptide (QK)-encapsulated nanoliposomes (QK-NLs@Gel) was first developed and used to repair a rat crush injury model. Our results showed that QK-NLs promoted the proliferation, migration, and angiogenesis of HUVEC via VEGF signaling pathway in vitro. Furthermore, when injected to the crushed sites in vivo, the QK-NLs@Gel hydrogel could accelerate nerve repair through enhanced revascularization and M2-polarization of macrophages. These results collectively demonstrate that injection of QK-NLs@Gel hydrogel could create an appropriate microenvironment for peripheral nerve regeneration. This strategy is effective, economical, and convenient for clinical applications.

Carcinoma ex pleomorphic adenoma of the submandibular gland: A retrospective analysis of 86 patients.

OBJECTIVES: To evaluate the prognostic and locoregional metastatic features of carcinoma ex pleomorphic adenoma of submandibular gland (SMG-CXPA) and improve the understanding of this uncommon condition. PATIENTS AND METHODS: We retrospectively reviewed patients who were diagnosed with SMG-CXPA. The survival data of SMG-CXPA patients were statistically analyzed using Cox regression and Kaplan-Meier method. The associations between cervical metastasis and clinicopathological parameters were evaluated using chi-squared test. Additionally, two different histological categories (histological grade and invasiveness) and their combination were evaluated with the Kaplan-Meier method and receiver operating characteristic curves. RESULTS: In total, 86 patients were diagnosed: 38 clinically node-negative, 31 pathologically node-negative, and 17 node-positive patients. Clinical tumor stage and histological grade were two independent prognostic factors for SMG-CXPA. There were significant correlations between sex, tumor size, clinical tumor stage, clinical lymph node stage, histological grade, invasiveness, malignant components, perineural invasion, and no specific criteria exist for the clinical outcome. CONCLUSION: SMG-CXPA is a high-grade malignancy with an unfavorable prognosis. Elective neck dissection should be performed in SMG-CXPA patients with a risk of locoregional metastasis. Histological grade seems to be a more valuable predictor of lymph node involvement than invasiveness.

Prognostic factors and treatment considerations of submandibular gland carcinomas: A population-based study.

OBJECTIVES: The therapeutic regimen of submandibular gland carcinoma (SGC) has not reached consensus, especially for the neck treatment of patients with cN0. MATERIALS AND METHODS: Patients with SGC were identified from the medical database of Shanghai Ninth People's Hospital. Kaplan-Meier analysis, univariate and multivariate Cox regression were employed to evaluate the survival and independent prognostic factors. RESULTS: Two hundred and fifteen patients with SGC were retrospectively reviewed. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 71.5% and 77.8%, respectively. Multivariate analysis revealed that histological grade, cT classification, cN classification, and perineural invasion (PNI) were independent prognostic factors for DFS, while histological grade, cT classification, cN classification, and age were those for OS. The neck dissection showed no significant survival benefit for patients with cN0. Lung was the most common site of distant metastasis (16.7%). CONCLUSIONS: Histological grade, cT classification, cN classification, age, and PNI were independent prognostic factors of patient with SGC, which should be the main considerations for making therapeutic regimens. Our study also verifies the neck dissection of patient with cN0 is unnecessary, and postoperative radiotherapy (PORT) is vital for patients with pN+.

Recurrent pleomorphic adenoma of the parotid gland: A population-based study with emphasis on re-recurrence and malignant transformation.

BACKGROUND: This study aimed to analyze the prognostic determinants for re-recurrence and malignant transformation of parotid recurrent pleomorphic adenoma (RPA). METHODS: Between January 2011 and December 2020, all the cases of RPA of the parotid gland at our single institution were reviewed. RESULTS: A total of 168 patients were included in this study, with a median age of 41.5 years, and 20 (11.9%) patients developed re-recurrence during follow-up. It has been evidenced that recurrence times (single or multiple) was an independent prognostic factor for recurrence-free survival (p = 0.0264). A total of 26 (15.48%) patients experienced malignant transformation of parotid RPA, and older age (>45 year old), male sex, and higher clinical tumor staging (T3-T4) were significantly associated with malignant transformation of parotid RPA. CONCLUSIONS: Recurrence times was an independent prognostic factor for re-recurrence of parotid RPA, and older male with high T-stage may more easily develop malignant transformation.

Flexible-in-rigid polycrystalline titanium nanofibers: a toughening strategy from a macro-scale to a molecular-scale.

TiO2 nanomaterials, especially one-dimensional TiO2 nanofibers fabricated by electrospinning, have received considerable attention in the past two decades, for a variety of basic applications. However, their safe use and easy recycling are still hampered by the inherently subpar mechanical performance. Here, we toughened polycrystalline TiO2 nanofibers by introducing Al3+-species at the very beginning of electrospinning. The resultant long-and-continuous TiO2 nanofibers achieved a Young's modulus of 653.8 MPa, which is ca. 25-fold higher than that of conventional TiO2 nanofibers. Within each nanofiber, amorphous Al2O3-based oxide effectively hindered the coalescence of TiO2 nanocrystals and potentially repaired the surface groves. The solid-state 17O-NMR spectra further revealed the toughening strategy on a molecular scale, where relatively flexible Ti-O-Al bonds replaced rigid O-Ti-O bonds at the interfaces of TiO2 and Al2O3. Moreover, the modified TiO2 nanofibers exhibited superb sinter-resistance, without cracking over 900 °C, which was dynamically monitored by TEM. Therefore, flexible-in-rigid TiO2 fibrous mats can be facilely folded into 3D sponges through origami art. As a potential showcase, the TiO2 sponges were demonstrated as a duarable and renewable filtrator with a high filtration efficiency of 99.97% toward PM2.5 and 99.99% toward PM10 after working for 300 min. This work provides a rational strategy to produce flexible oxide nanofibers and gives an in-depth understanding of the toughening mechanism from the macro-scale to the molecular-scale.

Adenoid cystic carcinoma of submandibular gland: Emphasis on locoregional metastasis and prognosis.

OBJECTIVES: To analyze the clinicopathological features, locoregional or distant metastasis, and prognosis of adenoid cystic carcinoma of submandibular gland (SMG-AdCC). METHODS: The clinicopathological data of 80 patients with SMG-AdCC from January 2005 to December 2017 were analyzed retrospectively, and the relationships between different parameters of SMG-AdCC and its locoregional or distant metastasis or prognosis were analyzed. RESULTS: As of December 2019, 41 patients (51.25%) were tumor-free, while 20 patients were found to be living with tumors. The locoregional metastasis rate of grade II-III SMG-AdCC were found to be significantly higher than that of grade I. The five-year DFS and OS rates were 70.8% and 87.1%, respectively. Univariate analysis showed that clinical size, extraglandular extension, pathological grade, pathological node (pN) status, and perineural invasion were correlated with DFS. Multivariate Cox regression analysis showed that pathological grade and extraglandular extension were independent prognostic factors for DFS; pN status and extraglandular extension were independent prognostic factors impacting OS. CONCLUSION: The pathological grade is a risk factor for locoregional metastasis of SMG-AdCC. Pathological grade, pN status, and status of extraglandular extension are independent prognostic factors for DFS/OS in SMG-AdCC patients.

Sustained delivery of vascular endothelial growth factor mediated by bioactive methacrylic anhydride hydrogel accelerates peripheral nerve regeneration after crush injury.

Neurotrophic factors, currently administered orally or by intravenous drip or intramuscular injection, are the main method for the treatment of peripheral nerve crush injury. However, the low effective drug concentration arriving at the injury site results in unsatisfactory outcomes. Therefore, there is an urgent need for a treatment method that can increase the effective drug concentration in the injured area. In this study, we first fabricated a gelatin modified by methacrylic anhydride hydrogel and loaded it with vascular endothelial growth factor that allowed the controlled release of the neurotrophic factor. This modified gelatin exhibited good physical and chemical properties, biocompatibility and supported the adhesion and proliferation of RSC96 cells and human umbilical vein endothelial cells. When injected into the epineurium of crushed nerves, the composite hydrogel in the rat sciatic nerve crush injury model promoted nerve regeneration, functional recovery and vascularization. The results showed that the modified gelatin gave sustained delivery of vascular endothelial growth factors and accelerated the repair of crushed peripheral nerves.

Calcitriol-enhanced autophagy in gingival epithelium attenuates periodontal inflammation in rats with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM)-associated periodontitis is a common disease with high prevalence, associated with persistent infection and complicated manifestations. Calcitriol (1 alpha, 25-dihydroxyvitamin D3, 1,25D) is the active form of vitamin D that plays a protective role in immune regulation, bone metabolism, and inflammatory response. In this study, we constructed a T2DM model in rats by combining a high-fat diet with low-dose streptozotocin. The periodontitis model in rats was developed by ligation and Porphyromonas gingivalis (ATCC 33277) inoculation. Rats were randomly divided into five groups: non-diabetic blank, diabetic blank, diabetes with calcitriol treatment, diabetes with 3-methyladenine (3-MA) treatment, or diabetes with calcitriol and 3-MA treatment. The diabetic rats exhibited an intense inflammatory response and decreased autophagy compared with the non-diabetic rats. Intraperitoneal injection of calcitriol and autophagy inhibitor (3-MA) allowed us to explore the effect of calcitriol on inflammation in the gingival epithelium and the role of autophagy in this process. Treatment with calcitriol resulted in the decreased expression of NFκB-p65, p62/SQSTM1 and inflammatory response and increased expression of LC3-II/LC3-I. Application of 3-MA significantly suppressed autophagy, which was apparently retrieved by calcitriol. Antibacterial peptide (LL-37) is the only antimicrobial peptide in the cathelicidin family that is found in the human body, and it exhibits a broad spectrum of antibacterial activity and regulates the immune system. In the present study, our findings indicated that calcitriol-enhanced autophagy may attenuated periodontitis and the decrease of LL-37 was rescued by calcitriol treatment in the gingival epithelial cells of T2DM rats. Our study provides evidence for the application of calcitriol as an adjunctive treatment for T2DM-associated periodontitis.

Integrative analysis of long non-coding RNAs and mRNAs associated with tumorigenesis of salivary gland pleomorphic adenoma.

OBJECTIVE: The current study investigated long non-coding RNA (lncRNA) and mRNA profiles of the human salivary gland pleomorphic adenoma (SGPA). DESIGN: Microarray analysis was used to study the expression of lncRNAs and mRNAs and the differentially expressed lncRNAs in human SGPA (all from parotid gland) were identified. The differentially expressed lncRNAs were subjected to qRT-PCR to verify and quantify their expression and a lncRNA-mRNA co-expression network was constructed. The lncRNAs correlated to pleomorphic adenoma gene 1 (PLAG1), a known key transcription factor, were identified and analyzed. RESULTS: In the present study, 17,382 lncRNAs and 8132 mRNAs were found to be significantly differentially expressed in SGPA (fold change > 2, P < 0.05). The expression of three lncRNAs (NR_110874, NR_110875 and T087085) was significantly altered in SGPA compared to the corresponding healthy tissues, and it was confirmed using the lncRNA-mRNA co-expression network analysis that several lncRNAs interact with 5 key regulators (PLAG1, CTNNB1, CCND1, IGF2, and TP53). Furthermore, T042819 was significantly upregulated in SGPA, which may upregulate PLAG1 by sponging has-miR195-5p. CONCLUSION: These data suggested that the differently expressed lncRNAs may contribute to the tumorigenesis of SGPA, and analyzing the differences in the lncRNA expression profiles may provide novel insights into the pathogenesis of SGPA.

Biocompatible Polyurethane Conduit Grafted with Vascular Endothelial Growth Factor-Loaded Hydrogel Repairs the Peripheral Nerve Defect in Rats.

Artificial nerve guidance conduits (NGCs) can be potentially used to address the problems of peripheral nerve defects. The biomaterial polyurethane (PU) has already been used to construct NGCs. However, the use of a combination of PU-based NGCs and other bioactive cues, such as extracellular matrix proteins and growth factors, has not been reported yet. A PU conduit grafted with a vascular endothelial growth factor (VEGF)-loaded hydrogel (abbreviated as PU/Gel/VEGF conduit) is fabricated. The leachate generated during the use of the PU/Gel/VEGF conduit could facilitate the proliferation, migration, and expression of the neural marker S100ß in RSC96 cells (in vitro). The walking track and target muscle are analyzed, and it is observed that PU/Gel/VEGF conduits promote the functional recovery of the injured side. Various histological staining analyses are carried out, and the results reveal that the PU/Gel/VEGF conduit effectively improves the extent of nerve regeneration achieved. The number of blood vessels developed during the regeneration of the axons in the PU/Gel/VEGF group (attributable to the pro-angiogenic effect of the functional NGC) is higher than the number of blood vessels developed in the PU/Gel conduit. Overall, the results indicate that PU/Gel/VEGF conduits could promote the process of peripheral nerve regeneration.

One stone two birds: a sinter-resistant TiO2 nanofiber-based unbroken mat enables PM capture and in situ elimination.

Airborne particulate matter (PM) primarily resulting from fossil fuel burning is an increasingly global issue. In this work, an intrinsically fragile TiO2 nanofibrous mat was facilely engineered with good structural integrity, flexibility, foldability, and high-temperature resistance (~1300 °C), by suppressing the sintering (i.e., growth) of nanocrystallites in each single nanofiber. Such functionalization enables self-regenerative air filtration for PM capture and in situ catalytic elimination in a "one-stone-two-birds" approach. Finite element analysis simulation revealed the retained nanopores in each anti-sintering nanofiber could facilitate the air flow during filtration. Without any chemical or physical modification, this self-standing and lightweight (7.1 g m-2) fibrous mat showed 96.05% filtration efficiency for 3-5 µm NaCl particles, with a low pressure drop of only 18 Pa and high quality factor of 0.179 Pa-1 under an airflow velocity of 32 L min-1. By utilizing its photocatalytic attribute, the nanofibrous mat in situ eliminated the captured particles from incense burning under one Sun irradiation in 4 h, and thereby spontaneously regenerated in an easy manner. The straightforward grafting of Au nanoparticles onto nanofibers could enable a quick degradation toward cigarette smoke, mainly due to the photothermally elevated local temperature by Au around the reactive sites. The plasmonic fibrous mat kept a high and stable filtration efficiency of PM0.3, PM2.5, and PM10 over 98.62%, 99.76%, and 99.99% during an outdoor long-term filtration test for 12 h under sunlight irradiation (Nanjing, China, September, 26th, 2020, 7:30 to 19:30). This work provides a solution for solving the airborne pollution from its source, prolonging the lifetime of the filter, and avoiding the risk of producing secondary pollution.

The Effects of Porphyromonas gingivalis on Inflammatory and Immune Responses and Osteogenesis of Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) are increasingly used in tissue regeneration, not only because of their multilineage differentiation ability, but also because of their immunomodulatory function, which allows them to play a role in the inflammatory milieu, especially in periodontitis. Porphyromonas gingivalis (P. gingivalis) is an important pathogen associated with the progression of periodontitis. Heterogeneous MSC sources show differences in their inflammatory-immune responsiveness and osteogenesis capabilities when exposed to P. gingivalis and its virulence factors. This article reviews the promoted inflammatory and immune responses of periodontal ligament stem cells, which are potential pitfalls in bone regeneration. MSCs from other sources showed contradictory inflammatory and immune reactions in the few studies on this topic. We also summarize the mechanisms involved in the inflammatory, immune responses and osteogenic potential of MSCs exposed to P. gingivalis and its virulence factors to inform an improved utilization of MSCs in regenerative therapies for periodontitis.

Role of CD44 in tumor-initiating cells of salivary gland pleomorphic adenoma: More than a surface biomarker.

CD44, a cell-surface glycoprotein, functions as a receptor for hyaluronic acid. Our research group has previously shown that CD44 is a biomarker for the CD44hi cells (tumor-initiating cells; TICs) in murine salivary gland tumors. However, little is known concerning the biological roles of CD44 in the tumorigenesis of pleomorphic adenoma. The present study is aimed to investigate the effects of CD44 on the proliferation, invasive capability, and apoptosis of TICs in vitro, as well as the tumorigenicity of TICs in vivo. The results demonstrated that knockdown of CD44 attenuated the malignant phenotype of TICs. Furthermore, in vivo xenograft studies indicated that CD44 knockdown inhibited tumorigenesis of pleomorphic adenoma. In addition, neither the CD44low cells nor the CD44-modified CD44low cells developed neo-tumors, which indicated that overexpression of CD44 did not enable the CD44low cells to be transformed into TICs. Taken together, these data demonstrate that CD44 not only acts as a biomarker, but also functions as a key player in the tumor-initiating capacity of TICs. These results shed light on the pathogenesis of salivary gland tumors and provide a potential therapeutic target for treating pleomorphic adenoma.