Implant stability changes over time following implant placement in elderly patients: A prospective study.

OBJECTIVES: This study aimed to evaluate the effect of aging on the changes in implant stability over time following implant placement. MATERIALS AND METHODS: A total of 104 patients in four age ranges (group 1: <60 years, group 2: 61-70 years, group 3: 71-80 years, and group 4: >80 years) were included. Bone-level tapered implants were placed without implementing any bone augmentation procedure. The final torque value displayed on the implant engine during implant insertion was recorded. Cone-beam computed tomography (CBCT) was performed immediately after surgery to analyze the bone quality around the implant. Implant stability was measured immediately after surgery and 2, 4, and 8 weeks after surgery. RESULTS: In the CBCT image, higher grayscale values were observed in the order of group 1, group 2, and groups 3/4, with statistical significance (p < .05). There was no significant difference in the insertion torque values between age groups (p ≥ .05). Groups 1 and 2 showed lower implant stability values after 2 and 4 weeks compared to immediately and 8 weeks after surgery (p < .05); however, groups 3 and 4 showed no significant difference between the results measured at different timepoints (p ≥ .05). CONCLUSIONS: Implant treatment in elderly patients is successful showing a settled implant stability over time following implant placement when the implant is appropriately engaged in the alveolar bone in the absence of bone augmentation.

Sympathetic Innervation of White Adipose Tissue: to Beige or Not to Beige?

Obesity research progresses in understanding neuronal circuits and adipocyte biology to regulate metabolism. However, the interface of neuro-adipocyte interaction is less studied. We summarize the current knowledge of adipose tissue innervation and interaction with adipocytes and emphasize adipocyte transitions from white to brown adipocytes and vice versa. We further highlight emerging concepts for the differential neuronal regulation of brown/beige versus white adipocyte and the interdependence of both for metabolic regulation.

Polarization of human gingival fibroblasts by Th1-, Th2-, Th17-, and Treg-derived cytokines.

BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate whether gingival fibroblasts (GFs) can be differently activated and polarized into distinct functional subtypes by T-helper (Th) cytokines. METHODS: Gingival fibroblasts were stimulated with interferon (IFN)-γ, interleukin (IL)-4, IL-17, and transforming growth factor (TGF)-ß, representative cytokines of Th1, Th2, Th17, and regulatory T cells, respectively, and the gene expression profiles were analyzed by microarray. Differentially expressed genes (DEGs) in GFs stimulated by 4 cytokines were screened, and a gene ontology (GO) analysis of the DEGs was conducted. To confirm the reliability of the microarray results, the DEGs that showed the largest differences compared with non-stimulated GFs were further analyzed by RT-PCR. To evaluate the effect of polarization on GFs responses to lipopolysaccharide (LPS), GFs stimulated by 4 cytokines were further stimulated with Escherichia coli LPS and mRNA levels of several genes were analyzed using RT-PCR. RESULTS: Differentially expressed genes by 4 Th cytokines were enriched in different GO terms, and the patterns of gene expression on GFs were shown functionally different. GFs stimulated with IFN-γ (GF(IFN-γ)) up-regulated the expression of chemokines (chemokine (C-X-C motif) ligand (CXCL)9, -10, -11, chemokine (C-C motif) ligand (CCL)8), molecules involved in antigen presentation, complement component 3 (C3), and other immune response-related molecules, whereas they down-regulated the expression of several types of collagen, extracellular matrix (ECM) components, and DNA replication and nuclear protein-related molecules. By contrast, GF(IL-4) up-regulated the expression of ECM components, cell adhesion molecules, and tissue development-related molecules and down-regulated the expression of chemokines (CXCL10 and CXCL8) and adaptive immune response-related molecules. GF(IL-17) up-regulated the expression of chemokines and other molecules for neutrophil infiltration and activation, the pro-inflammatory cytokine IL-6, and C3. GF(TGF-ß) up-regulated the expression of cell growth-related molecules, ECM components, several types of collagen, and cell adhesion molecules and down-regulated the expression of molecules related to complement activation and bacterial recognition. GFs stimulated by 4 cytokines responded differently to LPS. CONCLUSION: These results show that Th cytokines can polarize GFs into cells with functionally distinct features: immune-activating but tissue-destructive GF(IFN-γ), tissue-reparative, and immune-inhibiting GF(IL-4), highly pro-inflammatory GF(IL-17), and potent tissue-reparative GF(TGF-ß).

Protein arginine methyltransferase 1 contributes to the development of allergic rhinitis by promoting the production of epithelial-derived cytokines.

BACKGROUND: Arginine methylation is a posttranslational modification mediated by protein arginine methyltransferases (PRMTs). Although previous studies have shown that PRMT1 contributes to the severity of allergic airway inflammation or asthma, the underlying mechanism is poorly understood. OBJECTIVE: This study aimed to explore the role of PRMT1 and its relevant mechanism in the development of allergic rhinitis (AR). METHODS: The expression levels of PRMTs and cytokines were determined by RT-PCR, and the localization of PRMT1 was determined by immunohistochemistry and confocal microscopy. The levels of house dust mite (HDM)-specific immunoglobulins in serum and of cytokines in nasal lavage fluids were determined by ELISA. PRMT1 inhibition was achieved by siRNA and treatment with the pan PRMT inhibitor arginine N-methyltransferase inhibitor-1. RESULTS: PRMT1 expression was significantly increased in the nasal mucosa of patients and mice with AR. The degree of eosinophilic infiltration in the nasal mucosa was reduced in PRMT1+/- AR mice compared with wild-type mice. PRMT1 haploinsufficiency reduced the levels of HDM-specific immunoglobulins in serum and those of TH2 (IL-4, IL-5, and IL-13) and epithelial (thymic stromal lymphopoietin [TSLP], IL-25, and IL-33) cytokines in the nasal lavage fluids of AR mice. In nasal epithelial cells, HDM and IL-4 cooperate to enhance PRMT1 expression through a mitogen-activated protein kinase-dependent pathway. In addition, PRMT1 was essential for the production of TSLP, IL-25, and IL-33 in response to HDM and IL-4. Arginine N-methyltransferase inhibitor-1 treatment alleviated AR in the mouse model. CONCLUSIONS: PRMT1 plays an important role in AR development by regulating epithelial-derived cytokine production and might be a new therapeutic target for AR.

Melatonin Type 2 Receptor Activation Regulates Blue Light Exposure-Induced Mouse Corneal Epithelial Damage by Modulating Impaired Autophagy and Apoptosis.

The MT1/2 receptors, members of the melatonin receptor, belong to G protein-coupled receptors and mainly regulate circadian rhythms and sleep in the brain. Previous studies have shown that in many other cells and tissues, such as HEK293T cells and the retina, MT1/2 receptors can be involved in mitochondrial homeostasis, antioxidant, and anti-inflammatory responses. In our study, we aimed to investigate the effects of blue light (BL) exposure on the expression of melatonin and its receptors in the mouse cornea and to evaluate their functional role in corneal epithelial damage. After exposing 8-week-old C57BL/6 mice to BL at 25 and 100 J/cm2 twice a day for 14 days, a significant increase in the expression of 4-HNE and MT2 was observed in the cornea. MT2 antagonist-treated mice exposed to BL showed an increased expression of p62 and decreased expression of BAX and cleaved caspase 3 compared with mice exposed only to BL. In addition, MT2 antagonist-treated mice showed more enhanced MDA and corneal damage. In conclusion, BL exposure can induce MT2 expression in the mouse cornea. MT2 activation can modulate impaired autophagy and apoptosis by increasing the expression of BAX, an apoptosis activator, thereby regulating the progression of corneal epithelial damage induced by BL exposure.

Evaluation of microleakage and push-out bond strength of various composite resins for sealing the screw-access channel in implant-supported restorations.

STATEMENT OF PROBLEM: Microleakage and loss of the composite resin sealing the screw-access channel are frequent complications of screw-retained implant-supported prostheses. How the screw-access channel should be best restored to reduce such complications is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the microleakage and bond strength of 3 types of composite resins (flowable, packable, and bulk-fill) with or without a bonding agent treatment to seal the screw-access channel of 2 types of restorative materials (zirconia and Co-Cr alloy) with or without thermocycling. MATERIAL AND METHODS: In total, 240 yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) specimens (IPS e.max ZirCAD) and 240 Co-Cr alloy (Vera PDS) specimens were prepared with a Ø3×3-mm cylindrical cavity at the center to simulate the screw-access channel. Three types of composite resins (flowable, packable, and bulk-fill resin) (Filtek Z350 XT Flowable Restorative, Filtek Z350 XT Universal Restorative, and Filtek One Bulk Fill Restorative) were applied to restore the access channel of the zirconia and Co-Cr specimens with or without a bonding agent (Single Bond Universal Adhesive). Microleakage and push-out bond strength were determined and compared by dividing the specimens into experimental groups with or without thermocycling (1000 times with 30 seconds at 5 ±2 °C and 55 ±2 °C). The results were analyzed by using a 1-way ANOVA and 4-way ANOVA. Adjustment for multiple comparisons was made with the Tukey Honestly Significant Difference (HSD) test. RESULTS: The specimens subjected to thermocycling showed a lower bond strength (P<.001) and higher microleakage (P<.001) than specimens stored in a constant-temperature water bath. Specimens treated with bonding agents showed a higher bond strength (P<.001) and lower microleakage (P<.001) than specimens not treated with a bonding agent. Higher bond strengths were observed in the order of bulk-fill resin, packable resin, and flowable resin (P<.001). Packable resin showed higher microleakage than flowable resin and bulk-fill resin (P<.05). No significant difference in microleakage was found between the flowable resin and bulk-fill resin (P>.05). CONCLUSIONS: Higher bond strengths were observed in the order of bulk-fill resin, packable resin, and flowable resin. Less microleakage was observed in the flowable resin and bulk-fill resin than in the packable composite resin. Bonding agent treatment was effective in increasing bond strength and decreasing microleakage. Zirconia and Co-Cr showed a bond strength similar to that of composite resins, but zirconia showed higher microleakage than Co-Cr. Restoring the screw-access channel with the bulk-fill resin should increase bond strength and reduce microleakage.

Clinical Validation of Dental Implant Stability by Newly Designed Damping Capacity Assessment Device during the Healing Period.

Background and Objectives: To evaluate the stability of a dental implant and the effectiveness of a newly designed damping capacity assessment device by improving the number of blows and strength evaluated by a prospective clinical study. Materials and Method: The stability of dental implants was measured in 50 implants in a total of 38 patients. Measurements were performed using Anycheck and Periotest M devices, twice in total, divided into buccal and lingual directions. In addition, measurements were performed on the day of surgery, two weeks, one month, two months, and three months after surgery for a total of five times. After the standardization of the measured values, the differences and changes over time for each device were observed. Result: No difference in standardized values between the two devices was observed at any time point. In both devices, stability decreased at two weeks postoperatively but gradually increased thereafter. No differences were observed in the values according to the measurement direction. Conclusions: The damping capacity of Anycheck was similar to that of Periotest M. After a slight decrease in stability two weeks after implant placement, implant stability increased over time.

CD44v3-Positive Intermediate Progenitor Cells Contribute to Airway Goblet Cell Hyperplasia.

In allergic airway diseases, intermediate progenitor cells (IPCs) increase in number in the surface epithelium. IPCs arise from basal cells, the origin of hallmark pathological changes, including goblet cell hyperplasia and mucus hypersecretion. Thus, targeting IPCs will benefit future treatment of allergic airway diseases. However, the lack of adequate cell surface markers for IPCs limits their identification and characterization. We now show that CD44 containing exon v3 (CD44v3) is a surface marker for IPCs that are capable of both proliferating and generating differentiated goblet cells in allergic human nasal epithelium. In primary human nasal epithelial cells that had differentiated at an air-liquid interface, IL-4 upregulated mRNA expression of three CD44v variants that include exon v3 (CD44v3-v6, CD44v3,v8-v10, and CD44v3-v10), and it induced expression of CD44v3 protein in the basal and suprabasal layers of the culture. FACS analysis revealed two subpopulations differing in CD44v3 concentrations, as follows: CD44v3low cells expressed high amounts of proliferative and basal cell markers (Ki-67 and TP63), whereas CD44v3high cells strongly expressed progenitor and immature and mature goblet cell markers (SOX2, CA2, and SPDEF). Importantly, a blocking anti-CD44 antibody suppressed IL-4-induced mucin production by human nasal epithelial cells. Furthermore, CD44v3 was coexpressed with TP63, KRT5, or SOX2 and was upregulated in the basal and suprabasal layers of the nasal surface epithelium of subjects with allergic rhinitis. Taken together, these data demonstrate that high CD44v3 expression contributes to goblet cell hyperplasia in inflammation of the allergic airway.

Maternal cold exposure induces distinct transcriptome changes in the placenta and fetal brown adipose tissue in mice.

BACKGROUND: Brown adipose tissue (BAT) is specialized to dissipate energy in the form of heat. BAT-mediated heat production in rodents and humans is critical for effective temperature adaptation of newborns to the extrauterine environment immediately after birth. However, very little is known about whether and how fetal BAT development is modulated in-utero in response to changes in maternal thermal environment during pregnancy. Using BL6 mice, we evaluated the impact of different maternal environmental temperatures (28 °C and 18 °C) on the transcriptome of the placenta and fetal BAT to test if maternal cold exposure influences fetal BAT development via placental remodeling. RESULTS: Maternal weight gain during pregnancy, the average number of fetuses per pregnancy, and placental weight did not differ between the groups at 28 °C and 18 °C. However, the average fetal weight at E18.5 was 6% lower in the 18 °C-group compared to the 28 °C-group. In fetal BATs, cold exposure during pregnancy induced increased expression of genes involved in de novo lipogenesis and lipid metabolism while decreasing the expression of genes associated with muscle cell differentiation, thus suggesting that maternal cold exposure may promote fetal brown adipogenesis by suppressing the myogenic lineage in bidirectional progenitors. In placental tissues, maternal cold exposure was associated with upregulation of genes involved in complement activation and downregulation of genes related to muscle contraction and actin-myosin filament sliding. These changes may coordinate placental adaptation to maternal cold exposure, potentially by protecting against cold stress-induced inflammatory damage and modulating the vascular and extravascular contractile system in the placenta. CONCLUSIONS: These findings provide evidence that environmental cold temperature sensed by the mother can modulate the transcriptome of placental and fetal BAT tissues. The ramifications of the observed gene expression changes warrant future investigation.

IFN-γ or IL-4 polarization impacts the response of gingival fibroblasts to oral bacteria.

BACKGROUND AND OBJECTIVE: We previously reported that gingival fibroblasts (GFs) can be polarized into functionally distinct subtypes, immune-activating but tissue-destructive or tissue-reparative, in response to T helper (Th1) and Th2 stimuli, respectively. The purpose of this study was to evaluate the effect of polarization on GFs responses to oral bacteria. METHODS: Unprimed (GF(-)) and IFN-γ (GF(IFN-γ)) or IL-4 primed (GF(IL-4)) GFs were stimulated with live Fusobacterium nucleatum or Porphyromonas gingivalis. The mRNA expression of IL-1ß, IL-4, LPS-recognizing components (Toll-like receptor (TLR) 4, CD14), molecules involved in antigen presentation (human leukocyte antigen (HLA)-ABC, HLA-DP, CD74, CD40), chemokines (C-X-C motif chemokine (CXCL)10, CXCL11, chemokine (C-C motif) ligand 20 (CCL20)), collagen type 1 alpha 1 (COL1A1), and matrix metalloproteinase (MMP)-1, and the protein levels of IL-1ß, CD14, CXCL11, CCL20, and COL1A1 accumulated in supernatants were analyzed using real-time PCR and ELISA. RESULTS: In response to oral bacteria, the GF(IFN-γ) significantly upregulated the expression of LPS-recognizing components, molecules involved in antigen presentation, CXCL10, and CXCL11, whereas the levels of IL-4 and COL1A1 were downregulated, compared with GF(-). The levels of IL-1ß, CCL20, and MMP-1 from GF(IFN-γ) were differently regulated between both bacteria; F. nucleatum was synergistically upregulated, but P. gingivalis was downregulated. The GF(IL-4) stimulated with both bacteria upregulated the levels of IL-4, whereas the levels of TLR4 and chemokines were downregulated, compared with GF(-). The regulation of IL-1ß, CD14, CXCL11, CCL20, and COL1A1 proteins showed a similar tendency with mRNA regulation. CONCLUSION: Polarization of GFs with IFN-γ or IL-4 affected the way that GFs responded to oral bacteria through up or downregulation of inflammatory responses and extracellular matrix control.

Blue Light Induces Impaired Autophagy through Nucleotide-Binding Oligomerization Domain 2 Activation on the Mouse Ocular Surface.

In this study, we investigated the effects of blue light exposure on nucleotide-binding oligomerization domain 2 (NOD2) expression on the mouse ocular surface and evaluated the role of NOD2 activation in light-induced cell death. Mice were divided into wild-type (WT), NOD2-knock out (KO), WT + blue light (WT + BL), and NOD2-KO + blue light (NOD2-KO + BL) groups, and the mice in the WT+BL and NOD2-KO + BL groups were exposed to blue light for 10 days. After 10 days of blue light exposure, increased reactive oxygen species and malondialdehyde were observed in the WT + BL and NOD2-KO + BL groups, and the WT + BL group showed a higher expression of NOD2 and autophagy related 16 like 1. Although both WT+BL and NOD2-KO + BL groups showed an increase in the expression of light chain 3-II, NOD2-KO + BL mice had a significantly lower p62 expression than WT + BL mice. In addition, NOD2-KO+BL mice had significantly lower corneal epithelial damage and apoptosis than WT + BL mice. In conclusion, blue light exposure can induce impaired autophagy by activation of NOD2 on the ocular surface. In addition, the reactive oxygen species (ROS)-NOD2-autophagy related 16 like 1 (ATG16L) signaling pathway may be involved in the blue-light-induced autophagy responses, resulting in corneal epithelial apoptosis.

Ability of S100 proteins and matrix metalloproteinase-9 to identify periodontitis in a ligature-induced periodontitis dog model.

AIMS: The present study aimed to monitor the levels of selected salivary biomarkers during the development and treatment of periodontitis and to evaluate their ability to identify periodontitis in dogs. MATERIALS AND METHODS: A total of 15 beagle dogs were divided into a control group (no ligature), group 1 (ligature on six teeth), and group 2 (ligature on 12 teeth). The experimental periods consisted of 8 weeks of periodontitis induction and 4 weeks of treatment. Clinical measurements and the sampling of saliva were performed every 4 weeks. The levels of S100A8, S100A9, S100A8/A9, and matrix metalloproteinase (MMP)-9 were measured by enzyme-linked immunosorbent assay. RESULTS: All experimental animals and two control animals developed periodontitis, which was successfully treated. All salivary biomarkers were significantly increased in periodontitis with high diagnostic power (c-index ≥ 0.944) and were able to identify animals with periodontitis on a single tooth. Whereas the levels of salivary S100A8/A9 recovered to levels in health, those of S100A8, S100A9, and MMP-9 in periodontitis stability remained significantly higher than in health. CONCLUSION: Salivary S100A8, S100A9, S100A8/A9, and MMP-9 may be used for the screening of periodontitis in dogs, but with caution of other conditions that can affect their levels in saliva.

Air and Environmental Contamination Caused by COVID-19 Patients: a Multi-Center Study.

BACKGROUND: The purpose of this study was to determine the extent of air and surface contamination of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in four health care facilities with hospitalized coronavirus disease 2019 (COVID-19) patients. METHODS: We investigated air and environmental contamination in the rooms of eight COVID-19 patients in four hospitals. Some patients were in negative-pressure rooms, and others were not. None had undergone aerosol-generating procedures. On days 0, 3, 5, and 7 of hospitalization, the surfaces in the rooms and anterooms were swabbed, and air samples were collected 2 m from the patient and from the anterooms. RESULTS: All 52 air samples were negative for SARS-CoV-2 RNA. Widespread surface contamination of SARS-CoV-2 RNA was observed. In total, 89 of 320 (27%) environmental surface samples were positive for SARS-CoV-2 RNA. Surface contamination of SARS-CoV-2 RNA was common in rooms without surface disinfection and in rooms sprayed with disinfectant twice a day. However, SARS-CoV-2 RNA was not detected in a room cleaned with disinfectant wipes on a regular basis. CONCLUSION: Our data suggest that remote (> 2 m) airborne transmission of SARS-CoV-2 from hospitalized COVID-19 patients is uncommon when aerosol-generating procedures have not been performed. Surface contamination was widespread, except in a room routinely cleaned with disinfectant wipes.

Printing accuracy, mechanical properties, surface characteristics, and microbial adhesion of 3D-printed resins with various printing orientations.

STATEMENT OF PROBLEM: Printing orientation is an important decision in the initial steps of additive manufacturing, affecting printing accuracy and the mechanical properties of printed products. In addition, printing orientation determines the building direction of layers and the layer-by-layer configuration forming the surface geometry. PURPOSE: The purpose of this in vitro study was to evaluate the effect of printing orientation on the printing accuracy, flexural strength, surface characteristics, and microbial response of 3D-printed denture base resin. MATERIAL AND METHODS: Specimens were printed with denture base polymethyl methacrylate (PMMA) in 3 printing orientations (0, 45, and 90 degrees). The printing error rate, flexural strength, roughness, hydrophilicity, surface energy, and response to Candida albicans (C. albicans) were evaluated. RESULTS: Specimens printed at a 90-degree orientation showed the lowest error rates for length (P<.001), and those printed at a 45-degree orientation showed statistically higher error rates for thickness than those of other groups (P<.001). Flexural strength increased in order of the specimens printed at orientation degrees of 90<45<0 with statistical significance. The 45-degree oriented specimens showed higher roughness and surface energy than those of other groups (P<.001). A higher proportion of C. albicans was found in the specimens printed at orientation degrees of 90<45<0 with statistical significance. CONCLUSIONS: Printing orientation significantly influenced the printing accuracy, flexural strength, roughness, and response to C. albicans. Therefore, the printing orientation should be carefully decided to fabricate products with appropriate properties.

Integrins αvß5 and αvß6 Mediate IL-4-induced Collective Migration in Human Airway Epithelial Cells.

A positive link between persistent cellular motion and a defective tight junction barrier allows increased antigenic penetration and contact between ligand-receptor pairs, leading to exacerbated allergic airway inflammation and remodeling. Given that collective cell migration involves cell-cell and cell-extracellular matrix adhesions, and given that IL-4 induces epithelial barrier dysfunction and decreases cell-extracellular matrix adhesions, we hypothesized that IL-4 may induce collective migration in the well-differentiated primary human nasal epithelial cells (HNECs). Well-differentiated HNECs were treated with IL-4, and the effects of IL-4 on cell migration were investigated using genetic and pharmacological approaches, live-cell imaging, a vertex model, and immunostaining. IL-4 disrupted the expression and localization of the tight junction proteins zonula occludens 1 and occludin, and it induced the cleavage and asymmetric distribution of E-cadherin in the HNEC layers. It also induced collective epithelial migration and cell shape changes driven by actin cytoskeleton reorganization. In addition, the effect of IL-4 on collective HNEC migration was reversed by pharmacologic and genetic inhibition of the αv-integrin-activating enzyme furin, and function-blocking antibodies for αvß5 or αvß6. In IL-4-stimulated cells, both anti-αvß5 and anti-αvß6 inhibited the phosphorylation of focal adhesion kinase. Furthermore, both ß5- and ß6-integrins were enriched in basal cells in the injured airway epithelium with allergic rhinitis. These findings suggest that αvß5 and αvß6 serve as critical mechanoreceptors in IL-4-induced collective HNEC migration through the focal adhesion kinase signaling pathway. These results have implications for targeting treatment of exacerbation of respiratory allergic diseases.

Reprogramming of cancer stem cells into non-tumorigenic cells using stem cell exosomes for cancer therapy.

Cancer stem cells (CSCs) are a small population of cells with stem cell-like properties found in tumors. CSCs are closely associated with tumor heterogeneity, which influences tumor progress, metastasis, and drug resistance. Here, we propose a concept to enhance efficacy of cancer therapy through CSC reprogramming into non-tumorigenic cells using stem cell-derived exosomes with osteoinductive potential. We hypothesized that exosomes derived from osteogenic differentiating human adipose-derived stem cells (OD-EXOs) contain specific cargos capable of inducing osteogenic differentiation of CSCs. Quantitative RT-PCR analysis revealed that OD-EXOs enhanced the expression of osteogenic-related genes, such as alkaline phosphatase (ALPL), osteocalcin (BGLAP), and runt-related transcription factor 2 (RUNX2). In addition, expression of drug-resistance genes such as ATP binding cassette (ABC) transporter, the breast cancer gene family (BCRA1 and BCRA2), and the ErbB gene family were significantly decreased in OD-EXO-treated CSCs. Our findings suggest that OD-EXOs function as a biochemical cue for CSC reprogramming and contribute to overcoming therapeutic resistance.

Streptococcus koreensis sp. nov., Isolated from Human Subgingival Dental Plaque of Periodontitis Lesion.

A novel facultative anaerobic, Gram-stain-positive coccus, strain JS71T, was isolated from the human subgingival dental plaque of a periodontitis lesion. Phylogenetic analysis based on the 16S ribosomal RNA gene (16S rDNA) revealed that the strain belonged to the genus Streptococcus. The 16S rDNA sequence had high similarity with Streptococcus rubneri DSM 26920T (98.6%), Streptococcus parasanguinis ATCC 15912T (98.5%), and Streptococcus australis CCUG 45919T (98.3%). The genome of strain JS71T was 2,009,592 bp in length. The DNA G+C content of the strain was 42.1 mol%. Average nucleotide identity values between strain JS71T and S. rubneri DSM 26920T, S. parasanguinis ATCC 15912T, and S. australis CCUG 45919T were 88.9%, 80.8%, and 92.4%, respectively. Genome-to-genome distance values between strain JS71TS. rubneri DSM 26920T, S. parasanguinis ATCC 15912T, and S. australis CCUG 45919T were 36.5% (34-39%), 26.3% (23.9-28.7%), and 48.0% (45.4-50.6%), respectively. The major fatty acids of the strain were C16:0 (39.7%), C18:1 ω6c/C18:1 ω7c (15.5%), and C18:0 (10.4%). Based on these results, strain JS71T (= KCOM 2890T = JCM 33454T) should be a novel species of the genus Streptococcus, for which the name Streptococcus koreensis sp. nov. is proposed.

Prevotella koreensis sp. nov., Isolated from Human Subgingival Dental Plaque of Periodontitis Lesion.

A novel Gram-negative, obligately anaerobic, non-motile, non-spore forming, and rod-shaped bacterium, designated strain JS262T, was isolated from human subgingival plaque of periodontitis lesion and was characterized by polyphasic taxonomic analysis. Comparison of 16S ribosomal RNA gene (16S rDNA) sequence revealed that the strain belonged to the genus Prevotella. The percent similarity of 16S rDNA of strain JS262T was closest to those of Prevotella buccae ATCC 33574T (89.1%) and Prevotella shahii JCM 12083T (88.9%). The major fatty acids of strain JS262T were C16:0 (29.2%), iso-C15:0 (19.2%), and anteiso-C15:0 (16.9%). Complete genome of strain JS262T was 2,691,540 bp in length and the G+C content was 43.9 mol%. Average nucleotide identity and genome-to-genome distance values between strain JS262T and P. buccae ATCC 33574T or P. loescheii DSM 19665T were > 70.4% and > 30.1%, respectively. On the basis of these data, a novel Prevotella species is proposed: Prevotella koreensis sp. nov. The type strain of P. koreensis is JS262T (= KCOM 3155T = JCM 33298T).

NT-PGC-1α deficiency decreases mitochondrial FA oxidation in brown adipose tissue and alters substrate utilization in vivo.

Transcriptional coactivator PPAR γ coactivator (PGC)-1α and its splice variant N-terminal (NT)-PGC-1α mediate transcriptional regulation of brown adipose tissue (BAT) thermogenesis in response to changes in ambient temperature. PGC-1α is dispensable for cold-induced BAT thermogenesis as long as NT-PGC-1α is present. However, the functional significance of NT-PGC-1α in BAT has not been determined. In the present study, we generated NT-PGC-1α-/- mice to investigate the effect of NT-PGC-1α deficiency on adaptive BAT thermogenesis. At thermoneutrality, NT-PGC-1α-/- mice exhibited abnormal BAT phenotype with increased accumulation of large lipid droplets concomitant with marked downregulation of FA oxidation (FAO)-related genes. Consistent with transcriptional changes, mitochondrial FAO was significantly diminished in NT-PGC-1α-/- BAT. This alteration, in turn, enhanced glucose utilization within the NT-PGC-1α-/- BAT mitochondria. In line with this, NT-PGC-1α-/- mice had higher reliance on carbohydrates. In response to cold or ß3-adrenergic receptor agonist, NT-PGC-1α-/- mice transiently exhibited lower thermogenesis but reached similar thermogenic capacities as their WT littermates. Collectively, these findings demonstrate that NT-PGC-1α is an important contributor to the maintenance of FAO capacity in BAT at thermoneutrality and provide deeper insights into the relative contributions of PGC-1α and NT-PGC-1α to temperature-regulated BAT remodeling.

An unexpected role for the transcriptional coactivator isoform NT-PGC-1α in the regulation of mitochondrial respiration in brown adipocytes.

Brown adipose tissue dissipates energy as heat, a process that relies on a high abundance of mitochondria and high levels of electron transport chain (ETC) complexes within these mitochondria. Two regulators of mitochondrial respiration and heat production in brown adipocytes are the transcriptional coactivator PGC-1α and its splicing isoform NT-PGC-1α, which control mitochondrial gene expression in the nucleus. Surprisingly, we found that, in brown adipocytes, some NT-PGC-1α localizes to mitochondria, whereas PGC-1α resides in the nucleus. Here we sought to investigate the role of NT-PGC-1α in brown adipocyte mitochondria. Immunocytochemistry, immunotransmission electron microscopy, and biochemical analyses indicated that NT-PGC-1α was located in the mitochondrial matrix in brown adipocytes. NT-PGC-1α was specifically enriched at the D-loop region of the mtDNA, which contains the promoters for several essential ETC complex genes, and was associated with LRP130, an activator of mitochondrial transcription. Selective expression of NT-PGC-1α and PGC-1α in PGC-1α-/- brown adipocytes similarly induced expression of nuclear DNA-encoded mitochondrial ETC genes, including the key mitochondrial transcription factor A (TFAM). Despite having comparable levels of TFAM expression, PGC-1α-/- brown adipocytes expressing NT-PGC-1α had higher expression of mtDNA-encoded ETC genes than PGC-1α-/- brown adipocytes expressing PGC-1α, suggesting a direct effect of NT-PGC-1α on mtDNA transcription. Moreover, this increase in mtDNA-encoded ETC gene expression was associated with enhanced respiration in NT-PGC-1α-expressing PGC-1α-/- brown adipocytes. Our findings reveal a previously unappreciated and isoform-specific role for NT-PGC-1α in the regulation of mitochondrial transcription in brown adipocytes and provide new insight into the transcriptional control of mitochondrial respiration.