Bacterial Lipopolysaccharide Induces PD-L1 Expression and an Invasive Phenotype of Oral Squamous Cell Carcinoma Cells.

BACKGROUND: Expression of programmed death ligand-1 (PD-L1) is related to the prognosis of many solid malignancies, including oral squamous cell carcinoma (OSCC), but the mechanism of PD-L1 induction remains obscure. In this study, we examined the expression of PD-L1 and partial epithelial-mesenchymal transition (pEMT) induced by bacterial lipopolysaccharide (LPS) in OSCC. METHODS: The expression of Toll-like receptor 4 (TLR4) recognizing LPS in OSCC cell lines was analyzed. Moreover, the induction of PD-L1 expression by Porphyromonas gingivalis (P.g) or Escherichia coli (E. coli) LPS and EMT was analyzed by western blotting and RT-PCR. Morphology, proliferation, migration, and invasion capacities were examined upon addition of LPS. PD-L1 within EXOs was examined. RESULTS: PD-L1 expression and pEMT induced by LPS of P.g or E. coli in TLR4-expressing OSCC cell lines were observed. Addition of LPS did not change migration, proliferation, or cell morphology, but increased invasive ability. Moreover, higher expression of PD-L1 was observed in OSCC EXOs with LPS. CONCLUSION: Oral bacterial LPS is involved in enhanced invasive potential in OSCC cells, causing PD-L1 expression and induction of pEMT. The enhancement of PD-L1 expression after addition of LPS may be mediated by EXOs.

Incidence of antiresorptive agent-related osteonecrosis of the jaw: A multicenter retrospective epidemiological study in Hyogo Prefecture, Japan.

Background/purpose: The incidence of medication-related osteonecrosis of the jaw is increasing worldwide, mostly due to the use of antiresorptive agents (ARAs) such as bisphosphonate (BP) and denosumab (Dmab). However, the proportion of BP-related osteonecrosis of the jaw (BRONJ) and Dmab-related osteonecrosis of the jaw (DRONJ) among all ARA-related osteonecrosis of the jaw (ARONJ) cases is not clear; this hinders appropriate treatment, recurrence-prevention planning, and avoidance of unnecessary Dmab withdrawal. Moreover, the causative drug administered at each disease stage remains unknown. Therefore, we conducted a retrospective study of patients with ARONJ who visited oral and maxillofacial surgery departments at hospitals in Hyogo Prefecture, Japan, over 3 years to classify and compare patient characteristics with those having BRONJ and DRONJ. We sought to identify the proportion of DRONJ in ARONJ. Materials and methods: After excluding stage 0 patients, 1021 patients were included (471 high-dose; 560 low-dose). ARA treatment for bone metastases of malignant tumors and multiple myeloma was considered high dose, while that for cancer treatment-induced bone loss and osteoporosis was low dose. Results: Low doses of BP and Dmab accounted for >50% patients; the results differed from those in other countries. DRONJ accounted for 58% and 35% of high-dose and low-dose cases, respectively. Stage 3 ARONJ cases comprised 92 (19.5%) low-dose BRONJ, 39 (20.1%) high-dose BRONJ, 24 (30%) low-dose DRONJ, and 68 (24.5%) high-dose DRONJ. Eighty-nine patients who received switch therapy were divided into BRONJ or DRONJ, but there was no difference in the ratio of each stage compared to the non-switch therapy. Conclusion: To the best of our knowledge, this is the first study to clarify the proportion of BRONJ and DRONJ cases, causative drug, and its doses by disease stages. DRONJ accounted for approximately 30% of the ARONJ, approximately 60% of which was due to high doses.

G­CSF delays tooth extraction socket bone healing via the inhibition of bone turnover in mice.

Granulocyte colony-stimulating factor (G-CSF) regulates the survival, proliferation and differentiation of all cells in the neutrophil lineage, and is consequently used for neutropenic conditions. Upon G-CSF administration, osteoblasts and osteocytes are suppressed, and the support system allowing hematopoietic stem cells to remain in the microenvironment is diminished. The present study focused on and investigated G-CSF as a regulatory factor of bone remodeling. The aim of the present study was to investigate the effect of G-CSF administration on the bone healing of tooth extraction sockets. Significant differences in the bone volume fraction, and trabecular separation of the proximal femurs and alveolar septa were observed between the G-CSF and control (saline-treated) groups. The trabecular bone of the femur and alveolar septa was reduced in the G-CSF group compared with that in the control group. In addition, serum procollagen type 1 N-terminal propeptide levels, a marker of bone formation, were lower in the G-CSF group compared with in the control group. Fibrous connective tissues and immature bone were observed in the extraction socket, and bone healing was delayed in the G-CSF group compared with that in the control group. The bone area in the extraction socket 6 days after tooth extraction was significantly smaller in the G-CSF group (23.6%) than that in the control group (45.1%). Furthermore, G-CSF administration reduced the number of canaliculi per osteocyte and inhibited the connection of osteocyte networks. Consequently, osteoblast activation was inhibited and bone remodeling changed to a state of low bone turnover in the G-CSG group. Analysis of bone formation parameters revealed that the G-CSF group exhibited a lower mineral apposition rate compared with in the control group. In conclusion, these findings indicated that G-CSF may delay bone healing of the socket after tooth extraction.

Usefulness of quantitative bone SPECT/CT for evaluating medication-related osteonecrosis of the jaw treatment response.

OBJECTIVE: For assessment of therapeutic response in medication-related osteonecrosis of the jaw (MRONJ) cases, the clinical usefulness of quantitative bone single-photon computed tomography-computed tomography (SPECT/CT) results was investigated. MATERIALS AND METHODS: Sixteen patients (18 lesions) with a clinical diagnosis of MRONJ underwent bone SPECT/CT scanning before and during/after anti-inflammatory therapy given for 3 or more months. The GI-BONE software package was used to determine standard uptake values (SUVs), including maximum (SUVmax), peak (SUVpeak), and mean (SUVmean), and metabolic bone volume (MBV) and also total bone uptake (TBU). In both responders (downstage) and non-responders (upstage or no change), differences in quantitative values between the first and second SPECT/CT examinations were analyzed using a Wilcoxon test. RESULTS: Following therapy, significant reductions in SUVmax, SUVpeak, SUVmean, MBV and TBU values for 11 lesions were noted in the responders after therapy (p = 0.003, p = 0.006, p = 0.004, p = 0.003, and p = 0.002, respectively). On the other hand, those for the seven lesions in the non-responder group were not significantly different (p = 0.17, p = 0.16, p = 0.26, p = 0.96, and p = 0.12, respectively). Results for SUVmax change showed sensitivity and specificity values of 45.5% and 85.7%, respectively, for differentiating responders from non-responders, with - 37.3% the optimal cutoff value. Those for MBV change were 72.7 and 85.7%, respectively, with - 29.4% the optimal cutoff value. Those for TBU change were 81.8% and 85.7%, respectively, with - 36.3% the optimal cutoff value. CONCLUSION: The present findings showed that therapeutic response in MRONJ cases could be determined by use of quantitative SUV, MBV, and TBU values based on bone SPECT/CT findings.

Emotional modulation of cortical activity during gum chewing: A functional near-infrared spectroscopy study.

Distinct brain regions are known to be associated with various emotional states. Cortical activity may be modulated by emotional states that are triggered by flavors during food intake. We examined cortical activity during chewing with different flavors and assessed the emotional modulation of cortical activity using multichannel near-infrared spectroscopy. Thirty-six right-handed volunteers participated in this crossover trial. The participants experienced positive and negative emotions from chewing flavorful (palatable) or less flavorful (unpalatable) gums, respectively for 5 min. Participants rated the taste, odor, and deliciousness of each gum using a visual analog scale. Bilateral hemodynamic responses in the frontal and parietal lobes, bilateral masseter muscle activation, and heart rate were measured during gum chewing. Changes in all measured data during gum chewing were also evaluated. The ratings of the tastes and odors of each gum significantly differed among the participants (P < 0.001). Hemodynamic response changes were significantly elevated in the bilateral primary sensorimotor cortex during gum-chewing, in comparison to resting. The difference in hemodynamic responses between palatable and unpalatable gum conditions was detected in the left frontopolar/dorsolateral prefrontal cortex. Muscle activation and heart rate were not significantly different between different gum types. Our findings indicate that differential processing in the left prefrontal cortex might be responsible for the emotional states caused by palatable and unpalatable foods.

Establishment of an oral squamous cell carcinoma cell line expressing vascular endothelial growth factor a and its two receptors.

Background/purpose: Vascular endothelial growth factor receptor (VEGFR) expression in oral squamous cell carcinoma (OSCC) promotes tumor growth through both autocrine and paracrine signaling. VEGF-positive OSCC cases are associated with a high depth of invasion, increased metastasis, and poor prognosis. In this study we established and then molecularly and functionally analyzed an OSCC cell line that co-expresses VEGF-A, VEGFR-1, and VEGFR-2, termed HCM-SqCC010 cells. Materials and methods: VEGF-A, VEGFR-1, and VEGFR-2 expression in HCM-SqCC010 cells were examined by immunohistochemistry and immunoblotting. Expression and inhibition of VEGF-A, VEGFR-1, and VEGFR-2 in HCM-SqCC010 cells were verified by quantitative real-time PCR. Results: Our analysis of HCM-SqCC010 cells revealed that their proliferation depended on VEGF-A, and selective inhibition of VEGFR-1 or VEGFR-2 resulted in decreased cell growth. Conclusion: We established an OSCC cell line, HCM-SqCC010, that expresses VEGF-A, VEGFR-1, and VEGFR-2. This triple-positive cell line showed no effect from a molecular targeted drug toward VEGF-A, but it did show strong cell growth inhibition in response to a VEGFR inhibitor. Thus, new therapeutic strategies against OSCC should include a VEGFR inhibitor.

Relationships between cystatin C and creatinine-based eGFR with low tongue pressure in Japanese rural community-dwelling older adults.

BACKGROUND: Sarcopenia is prevalent in patients with chronic kidney disease (CKD), which is defined as a low estimated glomerular filtration rate (eGFR). It has been reported that oral hypofunction characterized by decreased tongue pressure is related to sarcopenia. Although there are several previous reports regarding the association of renal dysfunction with oral hypofunction characterized by low tongue pressure, the association between tongue pressure and renal function is not fully understood. METHODS: This cross-sectional study included 68 men aged 79.0 ± 4.8 years and 145 women aged 77.3 ± 5.4 years from a rural area in Hyogo Prefecture, Japan. We examined the relationships between cystatin C-based CKD (CKDcys), creatinine-based CKD (CKDcre), ratio of cystatin C-based GFR (eGFRcys) divided by creatinine-based GFR (eGFRcre): eGFRcys/eGFRcre, and tongue pressure in community-dwelling older adults. RESULTS: Tongue pressure was significantly lower in participants with CKDcys than in those without CKDcys in men and women. However, there were no significant differences in tongue pressure with or without CKDcre. Tongue pressure was significantly lower in participants with eGFRcys/eGFRcre <1.0, than in those with eGFRcys/eGFRcre ≧ 1.0 in men. According to the receiver operating characteristic analysis, the optimal cut-off value of tongue pressure for the presence of CKDcys was 36.6kPa, area under the curve (AUC) 0.74 (specificity 54.8%, sensitivity 84.6%) in men and 31.8kPa, AUC 0.65 (specificity 67.3%, sensitivity 60.5%) in women. CONCLUSIONS: CKDcys but not CKDcre is associated with low tongue pressure. In addition, a lower eGFRcys/eGFRcre ratio is a useful screening marker of low tongue pressure in community-dwelling older adults.

Relationship between Rate of Force Development of Tongue Pressure and Physical Performance.

In the assessment of skeletal muscle strength, rate of force development (RFD) is clinically identified as a functional index that reflects the effects of aging, but there are few reports on RFD of the tongue. The purpose of this study was to examine the relationship between RFD of tongue pressure (RFD-TP) and oral and whole-body physical performance in older adults, and to clarify its characteristics. We enrolled adults aged ≥65 years with pathological occlusal contact in premolar and molar regions of teeth in the Tamba-Sasayama area, Japan, from 2017 to 2018. Maximum tongue pressure (MTP) and the speed to reach the maximum tongue pressure (RFD-TP) were evaluated as measures of tongue function. Oral functions related to objective measures of tongue function, such as repetitive saliva swallowing test, oral diadochokinesis, and physical status or performance, such as mini mental state examination, body mass index, skeletal mass index, knee extension force, one-leg standing time, grip strength, walking speed, timed up-and-go test, and five-time chair stand speed was evaluated. No significant correlation was found between MTP and age, but RFD-TP had a significant negative correlation with age. Neither RFD-TP nor MTP showed a significant correlation with oral function. RFD-TP was associated with physical performance, such as knee extension force and one-leg standing time. RFD-TP is more sensitive to aging than MTP. In addition, RFD-TP is related to physical performance and may be useful for the early detection of frailty.

Establishment of a patient-derived mucoepidermoid carcinoma cell line with the CRTC1-MAML2 fusion gene.

Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the major and minor salivary glands. Surgical resection is the only curative treatment and there is no effective post-operative therapy for MEC. The present study reports an Institutional Review Board-approved case of a 45-year-old Japanese female diagnosed with low-grade MEC in the hard palate. Radical resection, supraomohyoid neck dissection and antero-lateral thigh flap reconstruction was performed. A MEC cell line was then established from the resected tumor tissue. Short tandem repeat profiling confirmed the origin and authenticity of the cell line, that harbors a CRTC1-MAML2 translocation, which is frequently observed in MEC. Amphiregulin (AREG), identified as one of the targets of the CRTC1-MAML2 fusion gene, was expressed in the cell line. The AREG receptor, epidermal growth factor receptor (EGFR) was also highly phosphorylated. The results predicted that AREG-EGFR signaling, which is required for tumor growth and survival, might be activated in the cell line in a cell-autonomous manner. As AREG expression is associated with EGFR-targeted drug resistance, this cell line might assist with the identification of novel strategies for MEC treatment.

The Association of Dietary Intake, Oral Health, and Blood Pressure in Older Adults: A Cross-Sectional Observational Study.

Hypertension is related to impaired mastication that causes malnutrition, declining the general health of older adults. This study assessed the role of dietary intake in the relationship between oral health and blood pressure. Eight hundred ninety-four adults aged ≥65 years who independently lived in rural regions of Japan participated in this study. Hypertension was classified according to the guidelines of the Japanese Society of Hypertension. The oral condition was evaluated by analyzing the remaining teeth, occlusal force, posterior occlusal support, masticatory performance, oral moisture, and oral bacterial level. Dietary intake was assessed using a brief self-administered dietary history questionnaire. Mann-Whitney U, chi-square, Kruskal-Wallis tests, and logistic regression analyses were used to elucidate the factors related to hypertension. Normotensive, hypertensive, and history of hypertension were observed in 30.9%, 23.8%, and 45.3% of the participants, respectively. The factors significantly associated with the hypertension were age, body mass index, posterior occlusal support condition, and sodium-to-potassium ratio related to salt intake and/or vegetable intake. Participants without posterior occlusion significantly had higher risk of hypertension (odds ratio = 1.72). This study suggested that there was an association between oral health and hypertension, while the loss of occlusal support may influence nutritional intake conditions.

Usefulness of quantitative bone SPECT/CT for medication-related osteonecrosis of the jaw in clinical settings.

OBJECTIVE: This study was conducted to investigate the clinical utility of quantitative bone single-photon computed tomography-computed tomography (SPECT/CT) for detection and classification for medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: Fifty-nine patients (69 lesions) clinically diagnosed as MRONJ by four specialists of Japanese Society of Oral Surgery according to the AAOMS diagnostic criteria and who underwent bone SPECT/CT were enrolled. One reader determined standard uptake values (SUVs), including maximum (SUVmax), peak (SUVpeak), and mean (SUVmean), as well as metabolic bone volume (MBV), representing total volume above threshold, and total bone uptake (TBU), calculated as MBV × SUVmean, using the GI-BONE software package. One-way repeated-measures analysis of variance and subsequent post hoc analysis were employed to compare quantitative values between clinical stages. To check reproducibility of values, another reader calculated these quantitative values. RESULTS: Mean SUVmax values for stage 0 (n = 21), 1 (n = 13), 2 (n = 25), and 3 (n = 10) were 5.82 ± 3.20, 5.46 ± 3.79, 8.16 ± 3.93, and 10.57 ± 8.43, respectively, while values for MBV were 9.52 ± 6.33, 11.36 ± 7.32, 12.4 ± 8.21, and 17.84 ± 16.94, respectively, and for TBU were 40.60 ± 46.97, 53.70 ± 77.26, 62.37 ± 42.91, and 102.01 ± 74.52, respectively. There were significant differences for SUVmax, SUVpeak, and SUVmean between clinical stages (p = 0.024, p = 0.027, p = 0.039, respectively). Subsequent post hoc analysis showed that SUVmax and SUVpeak of stage 3 were significantly higher than those of stage 0 (p = 0.046, 0.045, respectively). MBV and TBU showed a tendency to increase with increased stage, though differences between stages were not significant (p = 0.15, p = 0.053, respectively). Little differences of mean SUVmax, SUVpeak, SUVmean, MBV, and TBU between two readers were observed (- 3.10%, - 0.26%, - 4.24%%, 0.69%, and - 3.42%, respectively). The intraclass correlation coefficients (ICCs) of SUVmax, SUVpeak, SUVmean, MBV, and TBU were 0.985, 0.990, 0.980, 0.994, and 0.994, respectively (almost perfect for all values). CONCLUSION: As objective and reliable indicators, SUVmax and SUVpeak derived from quantitative bone SPECT/CT results are useful for detection of early status disease, as well as staging in MRONJ patients.

Estimation of Muscle Mass Using Creatinine/Cystatin C Ratio in Japanese Community-Dwelling Older People.

OBJECTIVES: Sarcopenia is defined as a combination of low skeletal muscle mass index (SMI), weak muscle strength, and reduced physical function. Recently, many studies have reported that the creatinine/cystatin C ratio (Cr/CysC) is useful for evaluating muscle mass. We designed a cross-sectional study with separate model development and validation groups to develop a prediction equation to estimate bioimpedance analysis (BIA)-measured SMI with Cr/CysC. DESIGN: The current study was a retrospective cross-sectional study. SETTING AND PARTICIPANTS: The model development group included 908 subjects (288 men and 620 women) from the Frail Elderly in the Sasayama-Tamba Area (FESTA) study, and the validation group included 263 subjects (112 men and 151 women) from participants in the medical checkup program at the Anti-Aging Center in Ehime Prefecture. MEASURES: Multivariate regression analysis indicated that age, hemoglobin (Hb), body weight (BW), and Cr/CysC were independently associated with SMI in both men and women. The SMI prediction equation was developed as follows: Men:4.17-0.012×Age+1.24×(Cr/CysC)-0.0513×Hb+0.0598×BW Women:3.55-0.00765×Age+0.852×(Cr/CysC)-0.0627×Hb+0.0614×BW RESULTS: The SMI prediction equation was applied to the validation group and strong correlations were observed between the BIA-measured and predicted SMI (pSMI) in men and women. According to the receiver operator characteristic (ROC) analysis, the areas under the curve were 0.93 (specificity 89.0%, sensitivity 87.2%) among men and 0.88 (specificity 83.6%, sensitivity 79.6%) among women for using pSMI to identify low SMI in the model development group. The pSMI also indicated high accuracy in ROC analysis for low SMI in the validation group. The Bland-Altman plot regression showed good agreement between BIA-measured and pSMI. CONCLUSIONS AND IMPLICATIONS: Our new prediction equation to estimate SMI is easy to calculate in daily clinical practice and would be useful for diagnosing sarcopenia.

The relationship between bone density and the oral function in older adults: a cross-sectional observational study.

BACKGROUND: Falls among older adults with a low bone density can lead to a bedridden state. Declining bone density increases the risk of falls resulting fractures in older adults. A person's physical performance is known to be closely related to bone density, and a relationship between the physical performance and the oral function is also known to exist. However, there currently is a lack of evidence regarding the relationship between bone density and the oral function. We assessed the relationship between the bone density and the both the oral function and physical performance among older adults. PATIENTS AND METHODS: 754 older adults aged 65 years or older who independently lived in rural regions and who were not taking any medications for osteoporosis participated. We checked all participants for osteoporosis using an ultrasonic bone density measuring device. Regarding the oral function, we evaluated the following factors: remaining teeth, occlusal support, masticatory performance, occlusal force, and tongue pressure. We also evaluated body mass index (BMI) and skeletal muscle mass Index as clinical characteristics. The normal walking speed, knee extension force and one-leg standing test were evaluated as physical performance. For the statistical analyses, we used the Mann-Whitney U test, chi-square test, the Kruskal-Wallis, and a multiple regression analysis. RESULTS: Eighty-one percent of the females and 58% of the males had osteoporosis or a decreased bone mass. The occlusal force, masticatory performance and the tongue pressure showed significant association with the bone density. The participants physical performance showed a significant association with their bone states except for walking speed. According to a multiple regression analysis, clinical characteristics (sex, age, BMI), one-leg standing and occlusal force showed independent associations with the bone density. It was suggested that the bone density tends to increase if the occlusal force is high and/or the one-leg standing test results are good. CONCLUSIONS: The bone density in the older adults showed a significant relationship not only with clinical characteristics or physical performance, but also with occlusal force. It may also be effective to confirm a good oral function in order to maintain healthy living for older adults.

Change in Nutritional Status and Dysphagia after Resection of Head and Neck Cancer.

Nutritional status is well-known to influence patient recovery after resection of head and neck cancer (HNC). The influence of preoperative nutritional status on dysphagia was assessed in patients who underwent surgical resection of HNC along with the assessment of nutritional status during the acute and subacute phases. Eighty-six patients underwent surgical resection and dysphagia assessments (repetitive saliva-swallowing test, water-swallowing test, and functional oral intake scale) and had their tongue pressure assessed five times (before surgery, after 1-2 weeks, and 1, 2, and 3 months after surgery). The nutritional status was assessed according to the body mass index, total protein, and albumin. The prognostic nutritional index was calculated from preoperative data, and the subjects were classified into three groups: Low-risk, Attention and High-risk groups. After surgery, the nutritional status index values were low, and the High-risk group showed significantly lower values in comparison to the other two groups. The water-swallowing test and functional oral intake scale findings were worse than they had been preoperatively until 2 months after surgery, and a significant correlation was noted between the postoperative nutritional status and the presence of dysphagia. The results indicated that the preoperative nutritional status of HNC patients influenced their ability to ingest/swallow, which in turn influenced their nutritional status after HNC resection.

Usefulness of Quantitative Bone SPECT/CT for Evaluating Treatment Response in a Patient with Mandibular Osteomyelitis.

We report here a case of mandibular osteomyelitis in a 63-year-old female in which quantitative values determined using bone SPECT/CT were useful to evaluate response to antibiotic therapy, hyperbaric oxygen therapy, and sequestomy. After finishing therapy, the chief complaints were well relieved, and posttreatment Tc-99m HMDP bone SPECT/CT examination showed decreased uptake. The maximum standardized uptake value (SUV), peak SUV, mean SUV, metabolic bone volume, and total bone uptake of the untreated lesion were 6.26, 5.16, 3.97, and 11.86 mL and 42.21, respectively, which were decreased to 4.65, 3.90, 2.77, and 9.67 mL and 26.80, respectively, following hyperbaric oxygen therapy and antibiotic administration, and were moreover decreased to 4.28, 3.67, 2.75, and 6.24 mL and 17.19, respectively, after sequestomy. In comparison with pretreatment situation, those parameters were decreased by -25.7, -24.4, -30.2, -18.5, and -36.5%, respectively, following hyperbaric oxygen therapy and antibiotic administration, and moreover by -31.6, -28.9, -30.7, -47.4, and -59.3, respectively, after sequestomy, likely reflecting treatment response. Quantitative bone SPECT/CT may be useful to evaluate bone inflammatory activity and treatment response in a patient with mandibular osteomyelitis.

Senescent RAW264.7 cells exhibit increased production of nitric oxide and release inducible nitric oxide synthase in exosomes.

Aging cells not only cease growing, but also secrete various proteins such as inflammatory cytokines. This secretory phenomenon is known as the senescence­associated secretory phenotype (SASP). The aim of the present study was to elucidate the effects of senescence on the differentiation of osteoclast precursors (OCPs) and corresponding SASP. RAW264.7 cells were used as OCPs and were cultured to passage (P)5, P10 and P20. Cell proliferation assays, senescence­associated ß­galactosidase staining and telomere length quantification were subsequently performed, and it was revealed that replicative senescence was induced at P20. In addition, the level of tartrate­resistant acid phosphatase activity in P20 cells treated with receptor activator of nuclear factor­κB ligand was significantly lower than that in P5 and P10 cells. The SASP factors interleukin­6, tumour necrosis factor­α and nitric oxide were significantly increased in P20 culture supernatants compared with those in P5 and P10 supernatants. Furthermore, the number of exosomes at P20 was increased compared with that at P5 and P10, and inducible nitric oxide synthase (iNOS) was expressed in exosomes at P20, but not in exosomes at P5. In conclusion, the present study revealed that senescent RAW264.7 cells exhibit increased expression of SASP factors and release iNOS in exosomes.

Association between Physical Frailty Subdomains and Oral Frailty in Community-Dwelling Older Adults.

This cross-sectional study aimed to demonstrate the association between physical frailty subdomains and oral frailty. This study involved community-dwelling older adults (aged ≥65 years). Physical frailty was assessed with the Japanese version of the Cardiovascular Health Study criteria. Oral frailty was defined as limitations in at least three of six domains. Logistic regression analysis was used to analyze the association between physical frailty risk and oral frailty. In addition, we examined the association between physical frailty subdomains (gait speed, grip strength, exhaustion, low physical activity, and weight loss) and oral frailty. A total of 380 participants were recruited for this study. Overall, 18% and 14% of the participants were at risk of physical frailty and had oral frailty, respectively. Physical frailty risk (odds ratio (OR) = 2.40, 95% confidence interval (CI): 1.22-4.75, p = 0.012) was associated with oral frailty in multivariate analysis. In secondary analysis, among physical frailty subdomains, gait speed (OR = 0.85, 95% CI: 0.73-0.97, p = 0.019) was associated with oral frailty. The present findings suggest that physical frailty is closely related to oral frailty. Among physical frailty subdomains, decreased gait speed in particular is an important indicator related to the development of oral frailty.

Low back pain is closely associated with frailty but not with sarcopenia: Cross-sectional study of rural Japanese community-dwelling older adults.

AIM: We speculated that low back pain, which is the most common ailment in older adults, is associated with frailty and/or sarcopenia and contributes to the progression of either condition. Our objective was to evaluate the relationship between low back pain, sarcopenia and frailty in rural Japanese community-dwelling older adults. METHODS: We recruited 730 participants aged ≥65 years who underwent a comprehensive health examination between November 2016 and December 2018. The Oswestry Disability Index (ODI) was used to assess low back pain quantitatively, and scores were compared for the frail groups determined by the Japanese version of Cardiovascular Health Study, and the sarcopenia groups as determined by the Asian Working Group for Sarcopenia 2019. RESULTS: Among 730 participants, the prevalence of low back pain was 57.8%. There were significant differences in the ODI scores between the robust, prefrail and frail groups (P < 0.001). In contrast, there were no significant differences in the ODI scores among the robust, low appendicular skeletal muscle and sarcopenia groups. Logistic regression analysis showed that the prevalence of low back pain and the ODI scores were significantly associated with frailty after adjustment for age, sex and body mass index (odds ratio 3.41, 95% confidence interval 1.39-8.39, P = 0.008, and odds ratio 1.06, 95% confidence interval 1.04-1.09, P < 0.001, respectively). CONCLUSIONS: To the best of our knowledge, this study is the first to show the close association between low back pain and frailty, and suggests that not only the decline in physical function but also neuropsychiatric factors, including chronic pain, constitute a vicious cycle of frailty in community-dwelling older adults. Geriatr Gerontol Int 2021; 21: 54-59.

Relationships between cystatin C- and creatinine-based eGFR in Japanese rural community- dwelling older adults with sarcopenia.

BACKGROUND: Sarcopenia is prevalent in patients with chronic kidney disease (CKD). The indices of physical function, such as grip power and gait speed, decreased according to the decline in the estimated glomerular filtration rate (eGFR). METHODS: We examined the relationships between cystatin C-based GFR (eGFRcys), creatinine-based GFR (eGFRcre), their ratio (eGFRcys/eGFRcre) and sarcopenia in community-dwelling older adults in Japan. This cross-sectional study included 302 men aged 73.9 ± 6.2 years and 647 women aged 72.9 ± 5.8 years from a rural area in Hyogo Prefecture, Japan. eGFRcys and eGFRcre were simultaneously measured, and sarcopenia based on the Asia Working Group for Sarcopenia (AWGS) 2019 criteria was evaluated. RESULTS: eGFRcys and the eGFRcys/eGFRcre ratio were significantly correlated with grip power and gait speed (p < 0.001). The eGFRcys/eGFRcre ratio was also correlated with skeletal muscle mass index (SMI) (p < 0.01). Univariate logistic regression analysis showed eGFRcys and eGFRcys/eGFRcre ratio but not eGFRcre were associated with sarcopenia (p < 0.01). The presence of low eGFRcys (CKDcys) and low eGFRcys/eGFRcre ratio (< 1.0) but not that of low eGFRcre (CKDcre) were associated with sarcopenia (p < 0.01). In the multivariate logistic regression analysis, when the eGFRcys/eGFRcre ratio was added as a covariate to the basic model, it was significantly associated with sarcopenia in women (p < 0.05). Moreover, low eGFRcys/eGFRcre ratio (< 1.0) was associated with a higher risk of sarcopenia in men (p < 0.01). CONCLUSION: In conclusion, CKDcys but not CKDcre is associated with sarcopenia. A lower eGFRcys/eGFRcre ratio may be a practical screening marker of sarcopenia in community-dwelling older adults.