Strategies for Overcoming Immune Evasion in Bladder Cancer.

Tumors intricately shape a highly immunosuppressive microenvironment, hampering effective antitumor immune responses through diverse mechanisms. Consequently, achieving optimal efficacy in cancer immunotherapy necessitates the reorganization of the tumor microenvironment and restoration of immune responses. Bladder cancer, ranking as the second most prevalent malignant tumor of the urinary tract, presents a formidable challenge. Immunotherapeutic interventions including intravesical BCG and immune checkpoint inhibitors such as atezolizumab, avelumab, and pembrolizumab have been implemented. However, a substantial unmet need persists as a majority of bladder cancer patients across all stages do not respond adequately to immunotherapy. Bladder cancer establishes a microenvironment that can actively hinder an efficient anti-tumor immune response. A deeper understanding of immune evasion mechanisms in bladder cancer will aid in suppressing recurrence and identifying viable therapeutic targets. This review seeks to elucidate mechanisms of immune evasion specific to bladder cancer and explore novel pathways and molecular targets that might circumvent resistance to immunotherapy.

IL-27-induced PD-L1highSca-1+ innate lymphoid cells suppress contact hypersensitivity in an IL-10-dependent manner.

Innate lymphoid cells (ILCs) play an important role in maintaining tissue homeostasis and various inflammatory responses. ILCs are typically classified into three subsets, as is the case for T-cells. Recent studies have reported that IL-10-producing type 2 ILCs (ILC210s) have an immunoregulatory function dependent on IL-10. However, the surface markers of ILC210s and the role of ILC210s in contact hypersensitivity (CHS) are largely unknown. Our study revealed that splenic ILC210s are extensively included in PD-L1highSca-1+ ILCs and that IL-27 amplifies the development of PD-L1highSca-1+ ILCs and ILC210s. Adoptive transfer of PD-L1highSca-1+ ILCs suppressed oxazolone-induced CHS in an IL-10-dependent manner Taken together, our results demonstrate that ILC210s are critical for the control of CHS and suggest that ILC210s can be used as target cells for the treatment of CHS.

Embryonic-stem-cell-derived mesenchymal stem cells relieve experimental contact urticaria by regulating the functions of mast cells and T cells.

Contact urticaria (CU) is an inflammatory skin disorder triggered by specific substances upon skin contact, leading to immediate acute or chronic manifestations characterized by swelling and redness. While mesenchymal stem cells (MSCs) are increasingly recognized for their therapeutic potential in immune diseases, research on the efficacy and mechanisms of stem cell therapy for urticaria remains scarce. This study investigates the regulatory role of embryonic-stem-cell-derived multipotent MSCs (M-MSCs) administered in a CU mouse model. Therapeutic effects of M-MSC administration were assessed in a Trimellitic anhydride-induced contact urticaria model, revealing significant inhibition of urticarial reactions, including ear swelling, itchiness, and skin lesion. Moreover, M-MSC administration exerted control over effector T cell activities in major lymphoid and peripheral tissues, while also suppressing mast cell degranulation in peripheral tissues. Notably, the inhibitory effects mediated by M-MSCs were found to be TGF-ß-dependent. Our study demonstrates the capacity of M-MSCs to regulate contact urticaria in a murine model, harmonizing the activation of inflammatory T cells and mast cells. Additionally, we suggest that TGF-ß derived from M-MSCs could play a pivotal role as an inhibitory mechanism in contact urticaria.

Intratubular crystal formation in the exposed dentin from nano-sized calcium silicate for dentin hypersensitivity treatment.

The aim of this study is to evaluate intratubular crystal formation from the experimental material consisting of dicalcium silicate (C2S) and tricalcium silicate (C3S) with nano-scaled particle size. A total of twenty-four specimens were made by isolating 8 mm of the cervical part centered at the cementoenamel junction of extracted premolars. Twelve specimens were not treated and considered as control. The experimental material was applied to the other twelve specimens by brushing for 10,000 strokes. Each group was randomly divided into four subgroups according to the period of immersion in phosphate buffer saline (PBS) for 1, 30, 60, and 90 days each. The specimens were sectioned longitudinally and examined with scanning electron microscopy and energy dispersion X-ray spectroscopy. The intratubular crystal were formed in PBS and densely filled the dentinal tubules over time. The crystal formation occurred at a depth of more than 50 µm from the dentin surface. The Ca/P ratio of formed intratubular crystals was 1.68 after 3 months. The experimental material consisting of C2S and C3S with a nanoscale particle size can form hydroxyapatite-like crystals in dentinal tubules in PBS, and there is a possibility of reducing dentin hypersensitivity by blocking the dentinal fluid flow.

Intravenous patient-controlled analgesia regimen in postoperative pain management following elective cesarean section: A single-center retrospective evaluation.

Intravenous patient-controlled analgesia (IV PCA; IVA) is the most widely used method for postoperative pain management. An appropriate IVA regimen is required, depending on the expected intensity of pain after surgery. This study expected that a decrease in the second prescription rate of IVA after elective cesarean section (CS) would help establish an appropriate regimen for the initial IVA. We retrospectively reviewed the records of 632 patients who were prescribed IVA after CS. We classified patients into phase 1 (basal rate 15.00 mcg/hours, bolus dose 15.00 mcg, total volume 100 mL) and phase 2 (basal rate 31.25 mcg/hours, bolus dose 31.25 mcg, nefopam 60 mg, paracetamol 3 g, total volume 160 mL) according to the IVA regimen, and patients in phase 2 were classified into the basal 15 group and basal 30 group according to the basal rate of IVA. We compared the rates of second prescription, drug removal, and side effects of IVA between the 2 phases and the 1 group. We analyzed the data of 631 eligible patients. The second prescription rate of IVA in phase 2 was 3.77%, a significant decrease compared to that in phase 1 (27.48%); however, the incidence of complications in phase 2 was 6.92%, a significant increase compared to that in phase 1 (0.96%). Within phase 2, in the basal 30 group, the basal rate was almost double that in the basal 15 group. However, there were no significant differences in the rate of second prescription, removed drug IVA, or adverse events between the basal 15, and 30 groups. In the case of CS, which has a high degree of postoperative pain, it is beneficial to control acute pain by properly setting the regimen of the initial IVA with a basal rate infusion to nullify a second prescription.

Influence of Phosphoric Acid Etching on Bond Strength for Calcium Silicate-Based Sealers.

INTRODUCTION: This study evaluated the microtensile bond strength of calcium silicate-based sealers and epoxy resin-based sealer, depending on the use of phosphoric acid (PA) etching before immediate resin restoration. METHODS: Exposed dentin surfaces of extracted human third molars were randomly assigned to 3 groups depending on sealer type (AH Plus [Dentsply DeTrey], CeraSeal [Meta Biomed Co.], and EndoSeal MTA [Maruchi]). Half of the samples were treated with PA for 30 seconds, and the other half were cleaned with water. Completely untreated specimens were used as controls. Self-etching adhesive (Clearfil SE Bond, Kuraray) was applied and composite resin (Tetric N-Ceram, Ivoclar Vivadent) was used to create build-ups. After 24 hours, the microtensile bond strength was measured (EZ Test, Shimadzu Co.). The failure mode was determined by light microscopy and scanning electron microscopy. One-way analysis of variance with the Bonferroni correction was used to analyze the data (P < .05). RESULTS: The bond strength of the water-washed dentin surfaces in the calcium silicate-based sealer groups did not differ significantly from those of the control surfaces but the PA-pretreated surfaces exhibited relatively low-bond strength. The AH Plus-treated group had lower bond strength than the control group when no PA treatment was applied, but PA treatment restored the bond strength. The adhesive failure mode was most frequently found in the AH Plus group without PA etching. CONCLUSIONS: When a water-soluble calcium silicate-based sealer is used, sufficient bond strength can be obtained by washing with water alone, with no need for PA use.

Evaluation of the clinical efficacy of quantitative light-induced fluorescence technology in diagnosing cracked teeth.

BACKGROUND: This retrospective study evaluated the clinical efficacy of quantitative light-induced fluorescence (QLF) technology for crack detection and the diagnosis of cracked teeth and assessed the possibility of a quantitative evaluation of cracks using QLF technology. METHODS: Patients who were clinically diagnosed with cracked teeth over a 1-year period were included. The QLF images of the corresponding symptomatic cracked teeth and asymptomatic contralateral teeth with crack lines were taken with Qraypen C (AIOBIO, Seoul, Korea). Fluorescence loss (ΔF), maximum fluorescence loss (ΔFmax), red fluorescence (ΔR), and maximum red fluorescence (ΔRmax) of the crack line were analyzed. The correlation between these parameters and sex, age, tooth position (1st premolar, 2nd premolar, 1st molar, 2nd molar), spontaneous pain (+/-), percussion test (+/-), cold test (++/+/-), and bite test (+/-) were statistically analyzed. RESULTS: A total of 66 patients were included. Twenty-four patients had asymptomatic contralateral teeth with apparent crack lines; thus, 90 teeth were analyzed. The crack lines in 84 teeth observed as red fluorescent lines on the QLF images showed ΔR values higher than the cut-off value set by the analysis program used. The patient's age and the ∣ΔF∣ and ΔR values were positively correlated. However, there was no statistically significant difference in the QLF parameters between the same patient's symptomatic tooth and the contralateral tooth. CONCLUSIONS: QLF technology is a useful assistive diagnostic device for diagnosing cracked teeth.

Deep learning for early dental caries detection in bitewing radiographs.

The early detection of initial dental caries enables preventive treatment, and bitewing radiography is a good diagnostic tool for posterior initial caries. In medical imaging, the utilization of deep learning with convolutional neural networks (CNNs) to process various types of images has been actively researched, with promising performance. In this study, we developed a CNN model using a U-shaped deep CNN (U-Net) for caries detection on bitewing radiographs and investigated whether this model can improve clinicians' performance. The research complied with relevant ethical regulations. In total, 304 bitewing radiographs were used to train the CNN model and 50 radiographs for performance evaluation. The diagnostic performance of the CNN model on the total test dataset was as follows: precision, 63.29%; recall, 65.02%; and F1-score, 64.14%, showing quite accurate performance. When three dentists detected caries using the results of the CNN model as reference data, the overall diagnostic performance of all three clinicians significantly improved, as shown by an increased sensitivity ratio (D1, 85.34%; D1', 92.15%; D2, 85.86%; D2', 93.72%; D3, 69.11%; D3', 79.06%; p < 0.05). These increases were especially significant (p < 0.05) in the initial and moderate caries subgroups. The deep learning model may help clinicians to diagnose dental caries more accurately.

The physical properties and anticariogenic effect of experimental resin cement containing ursolic acid.

The aim was to evaluate the physical properties and anti-bacterial activity of resin cement containing ursolic acid (UA) and determine the optimal concentration of UA. Five types of experimental resin cement were prepared according to UA concentration (0, 0.1, 0.5, 1.0, and 2.0 wt%). Flexural strength, film thickness and in vitro cytotoxicity were measured to confirm whether the resin was appropriate under International Organization for Standardization (ISO) criteria. Fifty extracted human molars were prepared, and indirect resin inlays were cemented with experimental resins. Acid-resistant nail varnish was applied, except for the 2-mm area around the restoration. Artificial caries were induced for 6 days through Streptococcus (S.) mutans (ATCC25175). Quantitative light-induced fluorescence (QLF) was used to evaluate the caries progression. One-way analysis of variance (ANOVA) followed by the Dunnett correction were used to statistically analyze the data. In all groups, the physical property of flexural strength, film thickness, and cytotoxicity were satisfied for ISO criteria (p > 0.05). On ∆F (-%) and ∆Q (-%⋅Px) values as QLF parameters, there was a tendency of being lower in groups of resin cement containing higher concentration of UA. Resin cement containing UA of greater than or equal to 0.5% significantly inhibited caries in the area around restoration (p < 0.05). There was no difference between the groups containing UA of greater than or equal to 0.5%. Resin cement containing 0.5% or more UA showed anti-carious effect in the limited range of 2% and satisfied the ISO criteria for flexural strength, film thickness and cytotoxicity.

Characterization of adipose-derived stromal/stem cell spheroids versus single-cell suspension in cell survival and arrest of osteoarthritis progression.

The current study evaluated the hypothesis that the administration of spheroidal adipose-derived stromal/stem cells (ASCs) promotes cell survival and arrests the progression of surgically induced osteoarthritis (OA) in a rat model. We also tested the optimal conditions for spheroid production from ASCs using microwell methods. The formation of ASC spheroids was optimized at a well diameter of 600 µm under cell concentrations of 106 cell/ml. When ASC spheroids cultured in 3D were compared with ASCs cultured in 2D monolayer, the cell survival and chondrogenic potential were enhanced while the apoptosis was reduced in ASC spheroids compared with ASCs in 2D monolayer culture. In vivo tracking of fluorescently labeled ASCs in the knee joints of rats with surgically induced OA showed longer fluorescent activity at a higher intensity in ASC spheroids than in ASC single-cell suspension. When OA-induced rats treated with ASC injection were sacrificed after 8 weeks, the OARSI score was enhanced in both ASC single-cell suspension and ASC spheroids compared with negative control, spheroid treatment resulting in a better score than single-cell treatment. However, injected cells were not detectable from the joints. These finding altogether suggests that ASC spheroids have better in vitro and in vivo survival and chondrogenic potential and exert greater regenerative effects for articular cartilage and arrest the progression of surgically induced OA better than ASCs in single-cell suspension by the paracrine mode of action. The study findings support the notion of developing cell therapeutics to treat OA based on ASC spheroid forms.

Sodium propionate exerts anticancer effect in mice bearing breast cancer cell xenograft by regulating JAK2/STAT3/ROS/p38 MAPK signaling.

Propionate is a short-chain fatty acid (SCFA) mainly produced from carbohydrates by gut microbiota. Sodium propionate (SP) has shown to suppress the invasion in G protein-coupled receptor 41 (GPR41) and GPR43-overexpressing breast cancer cells. In this study we investigated the effects of SP on the proliferation, apoptosis, autophagy, and antioxidant production of breast cancer cells. We showed that SP (5-20 mM) dose-dependently inhibited proliferation and induced apoptosis in breast cancer cell lines JIMT-1 (ER-negative and HER2-expressing) and MCF7 (ER-positive type), and this effect was not affected by PTX, thus not mediated by the GPR41 or GPR43 SCFA receptors. Meanwhile, we demonstrated that SP treatment increased autophagic and antioxidant activity in JIMT-1 and MCF7 breast cancer cells, which might be a compensatory mechanism to overcome SP-induced apoptosis, but were not sufficient to overcome SP-mediated suppression of proliferation and induction of apoptosis. We revealed that the anticancer effect of SP was mediated by inhibiting JAK2/STAT3 signaling which led to cell-cycle arrest at G0/G1 phase, and increasing levels of ROS and phosphorylation of p38 MAPK which induced apoptosis. In nude mice bearing JIMT-1 and MCF7 cells xenograft, administration of SP (20 mg/mL in drinking water) significantly suppressed tumor growth by regulating STAT3 and p38 in tumor tissues. These results suggest that SP suppresses proliferation and induces apoptosis in breast cancer cells by inhibiting STAT3, increasing the ROS level and activating p38. Therefore, SP is a candidate therapeutic agent for breast cancer.

An Immune-Magnetophoretic Device for the Selective and Precise Enrichment of Circulating Tumor Cells from Whole Blood.

Here, we validated the clinical utility of our previously developed microfluidic device, GenoCTC, which is based on bottom magnetophoresis, for the isolation of circulating tumor cells (CTCs) from patient whole blood. GenoCTC allowed 90% purity, 77% separation rate, and 80% recovery of circulating tumor cells at a 90 µL/min flow rate when tested on blood spiked with epithelial cell adhesion molecule (EpCAM)-positive Michigan Cancer Foundation-7 (MCF7) cells. Clinical studies were performed using blood samples from non-small cell lung cancer (NSCLC) patients. Varying numbers (2 to 114) of CTCs were found in each NSCLC patient, and serial assessment of CTCs showed that the CTC count correlated with the clinical progression of the disease. The applicability of GenoCTC to different cell surface biomarkers was also validated in a cholangiocarcinoma patient using anti-EPCAM, anti-vimentin, or anti-tyrosine protein kinase MET (c-MET) antibodies. After EPCAM-, vimentin-, or c-MET-positive cells were isolated, CTCs were identified and enumerated by immunocytochemistry using anti-cytokeratin 18 (CK18) and anti-CD45 antibodies. Furthermore, we checked the protein expression of PDL1 and c-MET in CTCs. A study in a cholangiocarcinoma patient showed that the number of CTCs varied depending on the biomarker used, indicating the importance of using multiple biomarkers for CTC isolation and enumeration.

Household food insecurity and dental caries in Korean adults.

OBJECTIVE: Food security is important to health maintenance and disease prevention. The aim of this study was to identify the association between household food insecurity and dental caries in Korean adults. METHOD: Data from 14 770 adults included in the 2013-2015 Korea National Health and Nutritional Survey were analysed. Household food insecurity was evaluated using the 18-item US Household Food Security/Hunger Survey Module. General characteristics differences based on household food security were compared with weighted one-way analysis of variance for continuous variables and weighted chi-squared tests for categorical variables. A modified Poisson approach was used to calculate prevalence ratios and 95% confidence intervals (95% CIs). RESULTS: The prevalence of untreated dental caries in permanent teeth was 28.9% (CI;27.6, 30.2), 36.7% (33.0, 40.5) and 48.9% (40.0, 57.8) among individuals with household food security, household food insecurity without hunger and household food insecurity with hunger, respectively. Relative to those who were food-secure, the prevalence ratios (95% CIs) for dental caries were 1.12 (0.97-1.31) and 1.35 (1.02-1.80) for those with household food insecurity without and with hunger, respectively, adjusting for age, sex, body mass index, socioeconomic status, life style, dietary and dental factors. CONCLUSION: We found that household food insecurity is associated with prevalence of untreated dental caries in Korean adults. Healthcare providers ought to consider the important role that food security can play in the prevention and management of oral health in adults.

KLF10 is a modulatory factor of chondrocyte hypertrophy in developing skeleton.

To define the functional role of Krüppel-like factor (KLF) 10 as a modulator of chondrocyte hypertrophy in developing skeleton, the developmental features in the long bone of KLF10 knockout (KO) mice were investigated and the mesenchymal stem cells (MSCs) from KLF10 KO mice were characterized regarding chondrogenesis and osteogenesis. Delayed long bone growth and delayed formation of primary ossification center were observed in an early embryonic stage in KLF10 KO mouse along with very low Indian hedgehog expression in epiphyseal plate. While the chondrogenic potential of mouse MSCs from KLF10 KO mice appeared normal or slight decreased, hypertrophy and osteogenesis were extensively suppressed. These findings suggest that KLF10 is a mediator of chondrocyte hypertrophy in developing skeleton, and that suppression of KLF10 may be employed as a new strategy for preventing hypertrophy in cartilage regeneration using MSCs.

Dual functional nanoparticles containing SOX duo and ANGPT4 shRNA for osteoarthritis treatment.

In our previous studies, we found that adult stem cells transfected with sex-determining region Y-box (SOX)-9, -6 and -5 genes (SOX trio) enhanced chondrogenesis and suppressed the progression of osteoarthritis (OA). The inhibition of angiopoietin-like 4 (ANGPT4) is known to reduce levels of cartilage damaging enzymes, such as, matrix metalloproteinases (MMPs). In this study, we designed nanoparticles comprising dexamethasone-conjugated polyethylenimine (DEX PEI) complexed with minicircle plasmid (MC) harboring SOX duo (SOX-9, -6) and ANGPTL4 small hairpin RNA (shANG) [MC SOX9/6/shANG] in the expectation that transfection of these nanoparticles would enhance chondrogenesis of stem cells and suppress inflammation in OA. Adipose-derived stem cells (ADSCs) transfected with MC SOX9/6/shANG (MC SOX9/6/shANG-tADSCs) showed significantly higher expressions of COL2 gene and protein than MC SOX9/6-transfected ADSCs (MC SOX9/6-tADSCs) during in vitro chondrogenesis while both enhanced chondrogenesis in the absence of growth factor addition as compared with negative controls. Furthermore, the expressions of MMP13 and MMP3 genes were significantly more diminished in MC SOX9/6/shANG-tADSCs than in MC SOX9/6-tADSCs. In vivo experiments using surgically-induced OA rats showed MC SOX9/6/shANG-tADSC-treated rats had significantly lower levels of cyclooxygenase (COX-2) and MMP13 in synovial fluids than MC SOX9/6-tADSC-treated rats, but no significant difference was observed between them in histological appearances. Both groups showed significantly less joint destruction than control groups did. These results demonstrate that dual functional nanoparticles containing SOX duo and ANGPT4 shRNA enhance chondrogenesis of ADSCs and suppress inflammation in OA. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:234-242, 2020.

Thyroid Hormone Receptor ß Inhibits Self-Renewal Capacity of Breast Cancer Stem Cells.

Background: A subpopulation of cancer stem cells (CSCs) with capacity for self-renewal is believed to drive initiation, progression, and relapse of breast tumors. Methods: Since the thyroid hormone receptor ß (TRß) appears to suppress breast tumor growth and metastasis, we have analyzed the possibility that TRß could affect the CSC population using MCF-7 cells grown under adherent conditions or as mammospheres, as well as inoculation into immunodeficient mice. Results: Treatment of TRß-expressing MCF-7 cells (MCF7-TRß cells) with the thyroid hormone triiodothyronine (T3) decreased significantly CD44+/CD24- and ALDH+ cell subpopulations, the efficiency of mammosphere formation, the self-renewal capacity of CSCs in limiting dilution assays, the expression of the pluripotency factors in the mammospheres, and tumor initiating capacity in immunodeficient mice, indicating that the hormone reduces the CSC population present within the bulk MCF7-TRß cultures. T3 also decreased migration and invasion, a hallmark of CSCs. Transcriptome analysis showed downregulation of the estrogen receptor alpha (ERα) and ER-responsive genes by T3. Furthermore, among the T3-repressed genes, there was an enrichment in genes containing binding sites for transcription factors that are key determinants of luminal-type breast cancers and are required for ER binding to chromatin. Conclusion: We demonstrate a novel role of TRß in the biology of CSCs that may be related to its action as a tumor suppressor in breast cancer.

Osteogenesis and angiogenesis are simultaneously enhanced in BMP2-/VEGF-transfected adipose stem cells through activation of the YAP/TAZ signaling pathway.

While bone has the capability to heal itself, there is a great difficulty in reconstituting large bone defects created by heavy trauma or the resection of malignant tumors. Also, osteonecrosis of the femoral head (ONFH), which is caused by obstruction of the blood supply to bone cells and occurs in the young, is not amenable for successful bone regeneration. We developed VEGF- and BMP2-transfected adipose stem cells (ASCs) using electroporation that can effectively treat bone defects by providing rapid angiogenesis and osteogenesis. The optimal ratio of BMP2- to VEGF-transfected ASCs to enhance both osteogenesis and angiogenesis was 9 : 1. BMP2-/VEGF-transfected ASCs administered in this ratio effectively healed critical-size calvarial defects and long-bone segmental defects in immunosuppressed rats. The implanted cells did not migrate out of the implantation site by the 56th day. TAZ, TEAD, and ANKRD1 were overexpressed in BMP2-/VEGF-transfected ASCs, possibly proposing the mechanism of enhanced bone regeneration and angiogenesis. Our results suggest the possibility of using gene-cell therapy that can induce rapid angiogenesis and osteogenesis in inhospitable avascular environments including large bone defects and ONFH.

miR-892b Inhibits Hypertrophy by Targeting KLF10 in the Chondrogenesis of Mesenchymal Stem Cells.

We investigated the functional role of miR-892b as a novel inhibitor of chondrocyte hypertrophy during TGF-ß-mediated chondrogenesis of human mesenchymal stem cells (hMSCs). The expression of miR-892b during TGF-ß-mediated chondrogenesis of hMSCs and the effects of miR-892b overexpression on chondrogenic and hypertrophic marker genes in the chondrogenesis of hMSCs were investigated. Targets of miR-892b were identified and verified by overexpression of synthetic miRNA mimics and luciferase assays. Cross-talk between Kruppel-like factor 10 (KLF10) and Indian hedgehog (Ihh) was investigated using KLF10 knockdown (KD). miR-892b enhanced chondrogenic makers and suppressed hypertrophy in hMSC chondrogenesis, mimicking parathyroid hormone-related peptide (PTHrP). KLF10, a transcription factor and miR-892b target, directly regulated Ihh promoter activity. Like miR-892b, KLF10 KD enhanced hMSC chondrogenesis and inhibited hypertrophy. Our findings suggest a key role of miR-892b in targeting the KLF10-Ihh axis as a regulator of hypertrophy in TGF-ß-mediated chondrogenesis of hMSCs and provide a novel strategy for preventing hypertrophy in chondrogenesis from MSCs.

Qualitative analysis on crystal growth of synthetic hydroxyapatite influenced by fluoride concentration.

OBJECTIVE: This study was designed to analyze the crystal growth of synthetic hydroxyapatite (HA) particles in pH 7.0 supersaturated solutions with different fluoride concentrations by FE-SEM, FE-TEM, X-ray diffraction (XRD), and FTIR. DESIGN: Eight groups of pH 7.0 calcium phosphate supersaturated solutions were prepared with different fluoride concentrations (0, 1, 2, 4, 8, 16, 32, and 64 ppm). Each solution was introduced into the reactive column containing the synthetic HA for 48 h. The resulting products were prepared for FE-SEM, FE-TEM, XRD, and FTIR. RESULTS: The FE-SEM examination revealed various morphological changes of the crystals, with additional, less-ordered crystallites in experimental solutions containing more than 8 ppm of fluoride. FE-TEM examination showed an additional amorphous layer on the surface of the crystals with the presence of fluoride, whereas definite lattice structures completely reached the surface of the crystals without fluorides. XRD data showed that all crystals had the same patterns as the unreacted synthetic HA, regardless of fluoride concentration. With FTIR results, the intensity of the OH-libration mode decreased when adding fluoride, compared to that of pristine HA. The resulting crystals were considered to be partially fluoridated HA under room temperature and pH 7.0 supersaturated solutions. CONCLUSION: Under the experimental conditions in this study, fluorides mainly react with the surface of the seed HA and have an impact on the growth of HA in a less effective manner as the concentration of fluoride increases.

Expression of C-type lectin receptor mRNA in otitis media with effusion and chronic otitis media with and without cholesteatoma.

BACKGROUND & OBJECTIVES: C-type lectin receptors (CLRs) are a family of pattern recognition receptors (PRPs). The expression of CLRs has been analyzed in other diseases but has not yet been compared in patients with otitis media with effusion (OME), chronic otitis media (COM) and COM with cholesteatoma (Chole OM). This study therefore evaluated the levels of expression of mRNAs encoding Dectin-1, MR1, MR2, DC-SIGN, Syk, Card-9, Bcl-10, Malt-1, Src, DEC-205, Tim-3, Trem-1, and DAP-12 in patients with OME, COM, and Chole OM. METHODS: CLR mRNA levels in patients with OME, COM, and Chole OM were assessed by real-time polymerase chain reaction. The level of expression of each mRNA was compared in patients with and without bacteria, and in patients with conductive hearing loss (CHL) and sensorineural hearing loss (SNHL). RESULTS: The patterns of expression of CLRs differed in patients with OME, COM, and Chole OM. Galectin-1 mRNA level was significantly higher in the COM than in the Chole OM group (p<0.05), and MR1 and Galectin-1 mRNA levels among patients with CHL were significantly higher in those with COM than with Chole OM (p<0.05). Galectin-1 mRNA level among patients with SNHL was also significantly higher in the COM than in the Chole OM group (p<0.05). CONCLUSIONS: The levels of expression of mRNAs encoding the CLRs Dectin-1, MR1, MR2, DC-SIGN, Syk, Card-9, Bcl-10, Malt-1, Src, DEC-205, Tim-3, Trem-1 and DAP-12 differ among patients with OME, COM, and Chole OM.