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Koji Naruishi,1,2 Akiko Kunita,3 Katsuyuki Kubo,1,2 Toshihiko Nagata,4 Shogo Takashiba,2,5 Seiji Adachi1 1Division of Local Care Center, Tottori Municipal Hospital, Tottori, Japan; 2Department of Periodontics and Endodontics, Okayama University Hospital, Okayama, Japan; 3Division of Rehabilitation, Tottori Municipal Hospital, Tottori, Japan; 4Department of Periodontology and Endodontology, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, Japan; 5Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan Purpose: The number of elderly inpatients has been steadily increasing worldwide. However, the ability to predict the degree of improvement of functional capacity after comprehensive examination of elderly inpatients is still lacking. The purpose of this study was to investigate the predictors of improved functional outcome after rehabilitation of elderly inpatients.Methods: We performed a retrospective cohort study with 1,079 patients (age

Background and Objectives: Diabetes mellitus (DM) is a risk factor for periodontal diseases and may exacerbate the progression of the pathogenesis of periodontitis. Advanced glycation end‐products (AGEs) cause DM complications relative to levels of glycemic control and larger amounts accumulate in the periodontal tissues of patients with periodontitis and DM. In the present study, we investigated the effects of AGEs on the expression of inflammation‐related factors in human gingival fibroblasts (HGFs) to elucidate the impact of AGEs on DM‐associated periodontitis. Material and Methods: HGFs were cultured with or without AGEs. Cell viability was examined, and RNA and protein fractions were isolated from AGE‐treated cells. The expression of interleukin (IL)‐6, intercellular adhesion molecule‐1 (ICAM‐1), and the receptor for AGE (RAGE) was investigated using reverse transcription‐polymerase chain reaction, quantitative real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay, and reactive oxygen species activity was measured using a kit with 2′,7′‐dichlorofluorescin diacetate. Human monocytic cells (THP‐1) labeled with a fluorescent reagent were co‐cultured with HGFs treated with AGEs and IL‐6 siRNA, and the adhesive activity of THP‐1 cells to HGFs was assessed. The expression of IL‐6 and ICAM‐1 was examined when HGFs were pretreated with recombinant human IL‐6, the siRNAs of RAGE and IL‐6, and inhibitors of MAPK and NF‐κB, and then cultured with and without AGEs. The phosphorylation of MAPK and NF‐κB was assessed using western blotting. Results: AGEs increased the mRNA and protein expressions of RAGE, IL‐6, ICAM‐1 and reactive oxygen species activity in HGFs, and promoted the adhesion of THP‐1 cells to HGFs, but had no effect on cell viability until 72 hours. Recombinant human IL‐6 increased ICAM‐1 expression in HGFs, while the siRNAs of RAGE and IL‐6 inhibited AGE‐induced IL6 and ICAM1 mRNA expression, and IL‐6 siRNA depressed AGE‐induced THP‐1 cell adhesion. AGEs increased the phosphorylation of p38 and ERK MAPKs, p65 NF‐κB and IκBα, while inhibitors of p38, ERK MAPKs and NF‐κB significantly decreased AGE‐induced IL‐6 and ICAM‐1 expression. Conclusion: AGEs increase IL‐6 and ICAM‐1 expression via the RAGE, MAPK and NF‐κB pathways in HGFs and may exacerbate the progression of the pathogenesis of periodontal diseases. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the relationship of the incidence of aspiration pneumonia with cognitive impairment and the oral condition. A total of 1,174 elderly patients were analyzed in a cross-sectional study. Cognitive function was evaluated using the Clinical Dementia Rating scale, and the oral condition was evaluated with inspection and palpation. Swallowing was examined in 196 patients using video-endoscopic evaluation. The Mann-Whitney U test and chi-square test were used for statistical analyses. Conditional logistic regression analysis was performed to compute odds ratios (OR) and 95% confidence intervals (CI). Loss of posterior occlusion, impaired tongue movements, and impaired cognition were factors significantly related to aspiration pneumonia. The incidence of aspiration pneumonia was higher in patients with both cognitive impairment and loss of posterior occlusion compared to those having either factor alone (OR: 5.16). There was no statistical association between impaired swallowing and the incidence of aspiration pneumonia in elderly patients with normal cognitive function (cognitive impairment, OR: 3.45; normal function, OR: 0.94). The authors concluded that co-existence of cognitive impairment and oral frailty significantly enhances the risk of aspiration pneumonia. Early and simple evaluation of the oral condition and cognitive function can predict the risk of aspiration pneumonia. [ABSTRACT FROM AUTHOR]

The type II interleukin-l receptor (IL-1RII) has been thought to be incapable of transducing signals to cells because of its short intracellular domain, while type I IL-1 receptor (IL-1RII does transduce signals. Since over-expression of IL-1RII has been demonstrated to inhibit cytokine production in the fibroblastic cell line, it has been proposed to use IL-1RII to prevent IL-1-induced inflammation in connective tissue. In this study, trace amounts of IL-1RII mRNA expression were detected in human gingival fibroblasts (HGFs), which are affected by cytokines in inflammatory periodontal disease. Cloning of the cDNA encoding IL-1RII expressed in HGFs revealed 3 amino acid substitutions in the extracellular domain, when compared with the 408 residues predicted from human B-cells. Over-expression of IL-1RII on HGFs by gene transfer down-regulated the expression of IL-1β mRNA and IL-6 mRNA in response to IL-β stimulation, while the expression of IL-8 mRNA was not affected. In the IL-1RII-transfected HGFs, phosphorylation of 25-and 74-kDa proteins was up-regulated upon IL-1β stimulation in the transfected HGFs. The phosphorylation of these proteins was suppressed by the addition of a neutralizing antibody against IL-1RII. These results suggest that the IL-1RII may regulate HGFs expression of cytokine mRNA upon IL-1β stimulation, possibly by altering the IL-1RI-dependent signals. [ABSTRACT FROM AUTHOR]

Background: Fibroblasts are known not only to synthesize and secrete extracellular matrix proteins, but also to degrade them for connective tissue remodeling. Drug-induced gingival overgrowth is characterized by a massive accumulation of extracellular matrix components in gingival connective tissues. Although some previous reports suggested that causative drugs stimulated the fibroblast proliferation, the results are not conclusive yet. In this study, we hypothesized that drug-induced gingival overgrowth could be a consequence of impaired ability of matrix degradation rather than an enhanced proliferation of gingival fibroblasts induced by these drugs.Methods: Normal human gingival fibroblasts were cultured with or without either 20 microg/ml of phenytoin or 200 ng/ml of cyclosporin A. Total RNA and cellular proteins were collected every day for RT-PCR analyses and for measuring lysosomal enzyme activity. In addition, an immunohistochemical study was performed to detect lysosomal enzymes in cells from enlarged gingiva of the patients with phenytoin-induced gingival overgrowth.Results: RT-PCR analyses revealed that these drugs suppressed the expression of MMP-1, TIMP-1, and cathepsin L, but not that of cathepsin B in a time-dependent manner. Then, we measured the activity of lysosomal enzymes and cathepsin B and L. The results indicated that although cathepsin B activity was not observed to be impaired, regardless of the drugs used in these cells, both total and active forms of combined activity of cathepsins B and L were suppressed in a time-dependent manner.Conclusions: The results indicate that, besides suggested effects of these drugs on gingival fibroblasts and/or on accumulated cells in the gingival tissues, extracellular matrix-degrading ability, particularly that by cathepsin L, is also suppressed by cyclosporin A and phenytoin in gingival fibroblasts, and that lysosomal enzyme plays an important role in the pathogenesis of drug-induced gingival hyperplasia. [ABSTRACT FROM AUTHOR]

Background and Objective: Lipocalin 2 (LCN2), a glycoprotein expressed in epithelial cells and leukocytes, has an antibacterial effect and plays a role in innate immunity. The delivery of LCN2 encapsulated in liposomes to oral epithelium may be useful to prevent oral infectious diseases. This study aimed to investigate the inhibitory effect of LCN2, artificially synthesized using a cell-free protein synthesis (CFPS) system, on the adhesion of Porphyromonas gingivalis to oral epithelial cells in order to approach oral healthcare using LCN2., Methods: LCN 2 was synthesized using a CFPS system and assayed by Western blotting, mass spectrometry and enzyme-linked immunosorbent assay (ELISA). The bilayer liposomes were prepared by the spontaneous transfer method using 1,2-dioleoyl-sn-glycero-3 phosphocholine (DOPC), 3-sn-phosphatidylcholine from Egg Yolk (Egg-PC), and 1,2-dioleoyl-sn-glycero-3 phosphoethanolamine (DOPE). The cellular and medium fractions derived from the culture of oral epithelial cells with liposome-encapsulated LCN2 were assayed by Western blotting and ELISA. The effect of the synthesized LCN2 on adhesion of the labeled P. gingivalis to oral epithelial cells was investigated as an evaluation of its antibacterial activity., Results: The synthesized LCN2 protein was identified by Western blotting; its amino acid sequence was similar to that of recombinant LCN2 protein. The additions of DOPE and octa-arginine in the outer lipid-layer components of liposome significantly increased the delivery of liposomes to epithelial cells. When oral epithelial cells were cultured with the synthesized and liposome-encapsulated LCN2, LCN2 was identified in the cellular and medium fractions by Western blotting and its concentration in the cellular fraction from the culture with the synthesized LCN2 was significantly higher than that of a template DNA-free protein. The synthesized LCN2 and liposome-encapsulated LCN2 significantly inhibited the adhesion of P. gingivalis to oral epithelial cells compared with template DNA-free protein., Conclusion: LCN2 was artificially synthesized by a CFPS system, encapsulated in liposomes, and delivered to oral epithelial cells, and demonstrated an antibacterial action against P. gingivalis. This approach may become a useful model for oral healthcare., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Candida albicans ( Ca ) is frequently detected in the peri-implant sulcus with peri-implantitis, a major postoperative complication after oral implant therapy. However, the involvement of Ca in the pathogenesis of peri-implantitis remains unclear. In this study, we aimed to clarify Ca prevalence in the peri-implant sulcus and investigated the effects of candidalysin (Clys), a toxin produced by Ca , on human gingival fibroblasts (HGFs). Peri-implant crevicular fluid (PICF) was cultured using CHROMagar and Ca colonization rate and colony numbers were calculated. The levels of interleukin (IL)-1β and soluble IL-6 receptor (sIL-6R) in PICF were quantified by enzyme-linked immunosorbent assay (ELISA). Pro-inflammatory mediator production and intracellular signaling pathway (MAPK) activation in HGFs were measured by ELISA and Western blotting, respectively. The Ca colonization rate and the average number of colonies in the peri-implantitis group tended to be higher than those in the healthy group. IL-1β and sIL-6R levels in the PICF were significantly higher in the peri-implantitis group than in the healthy group. Clys significantly induced IL-6 and pro-matrix metalloproteinase (MMP)-1 productions in HGFs, and co-stimulation with Clys and sIL-6R increased IL-6, pro-MMP-1, and IL-8 production levels in HGFs compared with Clys stimulation alone. These findings suggest that Clys from Ca plays a role in the pathogenesis of peri-implantitis by inducing pro-inflammatory mediators.

Periodontal diseases include periodontitis and gingival overgrowth. Periodontitis is a bacterial infectious disease, and its pathological cascade is regulated by many inflammatory cytokines secreted by immune or tissue cells, such as interleukin-6. In contrast, gingival overgrowth develops as a side effect of specific drugs, such as immunosuppressants, anticonvulsants, and calcium channel blockers. Human gingival fibroblasts (HGFs) are the most abundant cells in gingival connective tissue, and human periodontal ligament fibroblasts (HPLFs) are located between the teeth and alveolar bone. HGFs and HPLFs are both crucial for the remodeling and homeostasis of periodontal tissue, and their roles in the pathogenesis of periodontal diseases have been examined for 25 years. Various responses by HGFs or HPLFs contribute to the progression of periodontal diseases. This review summarizes the biological effects of HGFs and HPLFs on the pathogenesis of periodontal diseases.

Gan-Lu-Yin (GLY), a traditional Chinese herbal medicine, shows therapeutic effects on periodontitis, but that mechanism is not well known. This study aims to clarify the precise mechanism by investigating the inhibitory effects of GLY extracts on osteoclastogenesis in vitro and on bone resorption in periodontitis in vivo. RAW264.7 cells are cultured with soluble receptor activator of nuclear factor-kappa B (sRANKL) and GLY extracts (0.01-1.0 mg/mL), and stained for tartrate-resistant acid phosphatase (TRAP) to evaluate osteoclast differentiation. Experimental periodontitis is induced by placing a nylon ligature around the second maxillary molar in rats, and rats are administered GLY extracts (60 mg/kg) daily for 20 days. Their maxillae are collected on day 4 and 20, and the levels of alveolar bone resorption and osteoclast differentiation are estimated using micro-computed tomography (CT) and histological analysis, respectively. In RAW264.7 cells, GLY extracts significantly inhibit sRANKL-induced osteoclast differentiation at a concentration of more than 0.05 mg/mL. In experimental periodontitis, administering GLY extracts significantly decreases the number of TRAP-positive osteoclasts in the alveolar bone on day 4, and significantly inhibits the ligature-induced bone resorption on day 20. These results show that GLY extracts suppress bone resorption by inhibiting osteoclast differentiation in experimental periodontitis, suggesting that GLY extracts are potentially useful for oral care in periodontitis.

Background and Objectives: Diabetes mellitus (DM), a risk factor of periodontal diseases, exacerbates the pathological condition of periodontitis. A major factor for DM complications is advanced glycation end-products (AGEs) that accumulate in periodontal tissues and cause inflammatory events. Lipocalin 2 (LCN2) is an antimicrobial peptide and inflammation-related factor, and LCN2 levels increase in DM. In this study, the effects of AGEs and lipopolysaccharide of Porphyromonas gingivalis (P g-LPS) on LCN2 expression in human oral epithelial cells (TR146 cells) and the role of secreted LCN2 in periodontitis with DM were investigated., Material and Methods: TR146 cells were cultured with AGEs (AGE2) and control BSA and cell viability was estimated, or with P g-LPS. Conditioned medium and cell lysates were prepared from cultures of epithelial cells and used for Western blotting and ELISA to analyze LCN2, RAGE, IL-6, MAPK, and NF-κB. RNA was isolated from AGE-treated TR146 cells and differentiated HL-60 (D-HL-60) cells and used for quantitative real-time PCR to examine the expression of LCN2 and interleukin-6 (IL-6) mRNAs. RAGE- and LCN2-siRNAs (siRAGE, siLCN2) were transfected into epithelial cells, and AGE-induced LCN2 expression was investigated. D-HL-60 cells were co-cultured with TR146 cells that were transfected with siLCN2 and treated with AGEs, and IL-6 mRNA expression in D-HL-60 cells and cell migration was investigated., Results: AGEs increased the expression levels of LCN2 and IL-6 in oral epithelial cells. siRAGE and a neutralizing antibody for RAGE inhibited AGE-induced LCN2 expression. AGEs stimulated the phosphorylation of ERK, p38, and NF-κB in epithelial cells, and their inhibitors suppressed AGE-induced LCN2 expression. In contrast, P g-LPS did not show a significant increase in LCN2 level in TR146 cells that expressed Toll-like receptor 2. In co-culture experiments, AGE-induced LCN2 inhibited IL-6 mRNA expression in D-HL-60 cells, and LCN2 knockdown in epithelial cells suppressed HL-60 cell migration., Conclusion: These results suggested that AGEs increase LCN2 expression via RAGE, MAPK, and NF-κB signaling pathways in oral epithelial cells, and secreted LCN2 may influence the pathological condition of periodontitis with DM., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Calprotectin is a heterocomplex of S100A8 and S100A9 and is mainly secreted from neutrophils, monocytes, and chondrocytes in inflammatory condition. Calprotectin binds to RAGE and TLR4 and induces the expression of proinflammatory chemokines and cytokines in various cells. Periodontitis is a chronic inflammatory disease that leads to gingival inflammation and alveolar bone resorption. Calprotectin levels in gingival crevicular fluid of periodontitis patients are higher than healthy patients. In the present study, the effects of S100A8 and S100A9 on the expressions of proinflammatory cytokines and bone metabolism-related factors in mouse osteocyte-like cells (MLO-Y4-A2) were investigated., Design: MLO-Y4-A2 cells were treated with S100A8 and S100A9, and the expressions of RAGE, TLR4, RANKL, and several inflammatory cytokines were analyzed by PCR and Western blotting or ELISA methods. To investigate the intracellular signaling pathways, phosphorylation of MAPK and STAT3 was determined by Western blotting, and chemical specific inhibitors and siRNAs were used., Results: Expressions of IL-6 and RANKL were increased by treatment with S100A9 but not S100A8. However, both S100A8 and S100A9 did not change expression of IL-1 β , IL-8, and TNF- α . Although RAGE and TLR4 expressions were not upregulated by S100A9 treatment, transfection of siRNA for RAGE and TLR4 significantly decreased IL-6 and RANKL expressions. In addition, S100A9 activated p38, ERK, and STAT3 signaling pathways, and inhibitors for these factors significantly decreased S100A9-induced IL-6 and RANKL expressions., Conclusions: These results indicated that S100A9 induces IL-6 and RANKL production via engagement with RAGE and TLR4 signalings in osteocytes and suggested that S100A9 may play important roles in the periodontal alveolar bone destruction., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Ryosuke Takagi et al.)

Objectives: Infective endocarditis (IE) is a life-threatening infectious disease, but the pathogenesis of the disease remains uncertain. The objective of this study was to examine whether oral infectious conditions are associated with the occurrence of IE in valvular heart disease (VHD) patients., Materials and Methods: A total of 119 periodontitis (P) patients with or without VHD were enrolled, and cross-sectional analyses were performed. Patients were classified as follows: (1) mild-to-moderate P without VHD, (2) mild-to-moderate P with VHD, (3) severe P without VHD, or (4) severe P with VHD. A total of 78 VHD patients were classified as (1) VHD without IE or (2) VHD with IE. Conditional logistic regression analysis was performed to compute the odds ratio (OR) and 95% confidence interval (CI)., Results: No significant differences were observed between patients with or without VHD in oral conditions. A significant increase in the percentage of alveolar bone loss in VHD patients with IE was observed compared with that of patients without IE. The ratio of both Porphyromonas gingivalis (Pg) IgG titer > 1.68 and Pg fimA type II genotype in patients with IE was significantly higher than in patients without IE. There was a significant correlation between the occurrence of IE and clinical oral findings (number of remaining teeth: OR, 0.17; rate of alveolar bone loss > 40%: OR, 11.8)., Conclusions: VHD patients with IE might have severe periodontitis compared with patients without IE, although further investigation will be needed because this is based on only 7 VHD patients with IE., Clinical Relevance: The patients with IE had fewer remaining teeth, more advanced bone resorption compared with those of patients without IE. These findings suggest a possible association between the occurrence of IE and periodontal infection.

Periodontitis is a polymicrobial infectious disease that leads to inflammation of the gingiva, resulting in teeth loss by various causes such as inflammation-mediated bone resorption. Recently, many investigators have reported that the periodontitis resulting from persistent low-grade infection of Gram-negative bacteria such as Porphyromonas gingivalis ( Pg ) is associated with increased atherosclerosis, diabetes mellitus, and other systemic diseases through blood stream. On the other hand, carotenoids belong among phytochemicals that are responsible for different colors of the foods. It is important to examine whether carotenoids are effective to the inhibition of periodontal infection/inflammation cascades. This review summarizes the advanced state of knowledge about suppression of periodontal infection by several carotenoids. A series of findings suggest that carotenoids intake may provide novel strategy for periodontitis treatment, although further study will be needed.

Advanced glycation end-products (AGEs) cause diabetes mellitus (DM) complications and accumulate more highly in periodontal tissues of patients with periodontitis and DM. AGEs aggravate periodontitis with DM by increasing the expression of inflammation-related factors in periodontal tissues. 6-Shogaol, a major compound in ginger, has anti-inflammatory and anti-oxidative activities. However, the influence of shogaol on DM-associated periodontitis is not well known. In this study, the effects of 6-shogaol on AGEs-induced oxidative and anti-oxidative responses, and IL-6 and ICAM-1 expression in human gingival fibroblasts (HGFs) were investigated. When HGFs were cultured with 6-shogaol and AGEs, the activities of reactive oxygen species (ROS) and antioxidant enzymes (heme oxygenase-1 [HO-1] and NAD(P)H quinone dehydrogenase 1 [NQO1]), and IL-6 and ICAM-1 expressions were investigated. RAGE expression and phosphorylation of MAPKs and NF-κB were examined by western blotting. 6-Shogaol significantly inhibited AGEs-induced ROS activity, and increased HO-1 and NQO1 levels compared with the AGEs-treated cells. The AGEs-stimulated expression levels of receptor of AGE (RAGE), IL-6 and ICAM-1 and the phosphorylation of p38, ERK and p65 were attenuated by 6-shogaol. These results suggested that 6-shogaol inhibits AGEs-induced inflammatory responses by regulating oxidative and anti-oxidative activities and may have protective effects on periodontitis with DM., Competing Interests: All authors have no conflicts of interest related to this study.

Sclerostin is a secreted glycoprotein that is mainly expressed in osteocytes, exerts negative effects on bone formation, and is present at elevated levels in diabetes mellitus (DM). Periodontitis is an infectious disease caused by periodontopathic bacteria, a complication of DM, and sometimes associated with severe inflammation and alveolar bone resorption. Advanced glycation end-products (AGEs) are a major pathogen in DM complications and adversely influence periodontitis in DM patients. In the present study, the effects of AGE2 and Porphyromonas gingivalis lipopolysaccharide (P-LPS) on the expression of sclerostin in mouse osteocyte-like cells (MLO-Y4-A2 cells) and its function in osteoblast differentiation were investigated. AGE2 and P-LPS up-regulated the expressions of receptor of AGE (RAGE) and Toll-like receptor 2 (TLR2), respectively, and significantly up-regulated that of sclerostin and interleukin 6 (IL-6) in osteocytes. Sclerostin, RAGE and TLR2 levels were synergistically increased by AGE2 and P-LPS. The siRNAs of RAGE and TLR2 significantly inhibited AGE2- and P-LPS-induced sclerostin expression. AGE2 up-regulated sclerostin expression in osteocyte-like cells via the RAGE, ERK and JNK, and NF-κB signal pathways. On the other hand, P-LPS elevated sclerostin levels via the TLR2, JNK and p38, and NF-κB signal pathways. When osteocytes pre-treated with AGE2 and P-LPS and osteoblastic cells (MC3T3-E1) were co-cultured in the medium with a sclerostin-neutralizing antibody, AGE2- and P-LPS-induced decreases in alkaline phosphatase activity and Runx2 expression in osteoblastic cells were significantly inhibited by the sclerostin-neutralizing antibody. These results suggest that AGE2 and P-LPS influence bone metabolism and inflammation through the regulation of sclerostin expression, and may aggravate periodontitis with DM., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The objective of this study was to investigate the relationship of the incidence of aspiration pneumonia to cognitive impairment and the oral condition., Materials and Methods: A total of 1174 elderly patients were analyzed in a cross-sectional study. Cognitive function was evaluated by the Clinical Dementia Rating scale and the oral condition was evaluated by inspection and palpation. Swallowing was examined in 196 patients by video-endoscopic evaluation. The Mann-Whitney U test or chi-square test was used for statistical analysis. Conditional logistic regression analysis was performed to compute the odds ratio (OR) and 95% confidence interval (CI)., Results: Loss of posterior occlusion, impaired tongue movements, and impaired cognition were factors significantly related to aspiration pneumonia. The incidence of aspiration pneumonia was higher in patients with both cognitive impairment and loss of posterior occlusion compared with those having either factor alone (OR: 5.16). There was no statistical association between impaired swallowing and the incidence of aspiration pneumonia in elderly patients with normal cognitive function (cognitive impairment, OR: 3.45; normal function, OR: 0.94)., Conclusion: Co-existence of cognitive impairment and oral frailty significantly enhances the risk of aspiration pneumonia., Clinical Relevance: Early and simple evaluation of the oral condition and cognitive function can predict the risk of aspiration pneumonia.

Background: There is limited information on the relationship of low body mass index (BMI) to the geriatric conditions in elderly patients., Objective: The objective of this study is to investigate whether low BMI associates with geriatric status in elderly patients by calculating suitable cut-off point of BMI for assessment of geriatric conditions., Method: A total of 1223 elderly patients was enrolled (male/female: N = 472/751), and cut-off point of the BMI values to assess the geriatric status such as aspiration pneumonia, cognitive impairment was determined by receiver operating characteristic (ROC) analyses. Logistic regression analyses were performed to examine the association between several geriatric status and low BMI. Of these patients, 262 patients (male/female: 101/161) had received standard rehabilitation treatment. Functional Independence Measure (FIM) scores were measured both at admission and discharge to calculate FIM gain and efficiency, and retrospective cohort study was performed., Results: Cut-off point of BMI value to assess the geriatric status was determined (19.0 kg/m 2 ). Significant associations of low BMI to several geriatric factors such as loss of posterior occlusion, cognitive impairment were observed in both male and female. FIM scores in above cut-off point group were significantly higher than in below cut-off point group in female (FIM gain, P = 0.0005; FIM efficiency, P = 0.0025, Mann-Whitney U test). On the other hand, there were no significant differences between low and above BMI cut-off point in FIM scores of male patients., Conclusion: Low BMI might be a useful parameter to evaluate the geriatric status, and the viewpoint would contribute to decide the care plan for the good end-of-life of elderly., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Periodontitis is a bacterial infectious disease, and many inflammatory cytokines regulate periodontitis pathophysiology through a crosstalk between tissue cells and immune cells. Interleukin (IL)-6 is an important cytokine involved in the regulation of host response to bacterial infection. Human Gingival Fibroblasts (HGFs) are the most abundant cells in gingival connective tissues. Various HGF responses to periodontal pathogens or inflammatory cytokines contribute to the development of periodontitis. Lipopolysaccharide derived from Porphyromonas gingivalis (Pg LPS) and IL-1β significantly increase IL-6 production in HGFs. However, IL-6 cannot function in HGFs without the soluble form of the IL-6 receptor (sIL-6R), because HGFs do not express sufficient cell surface IL-6R to bind appreciable levels of IL-6. Importantly, sIL-6R is essential for IL-6 signaling in HGFs, and the sIL-6R is produced by differentiated THP-1 cells treated with IL-6. Calprotectin, a heterodimer of S100A8 and S100A9, is released during inflammation and significantly induces IL-6 production in HGFs via toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signals. Calprotectin also induces sIL-6R production in differentiated THP-1 cells. IL-6 induces vascular endothelial growth factor (VEGF), matrix-metalloproteinase-1 (MMP-1), and cathepsin L production in HGFs in the presence of sIL-6R. Taken together, calprotectin-induced IL-6 production in HGFs may cause periodontitis progression through a crosstalk of fibroblasts and macrophages. There are many reports that examine how cytokines are released from HGFs to cause beneficial or harmful effects in inflamed periodontal lesions. This review explores the pathophysiology of periodontitis by focusing IL-6-mediated crosstalk of HGFs and macrophages., (© 2018 Wiley Periodicals, Inc.)