Long-term caloric restriction ameliorates T cell immunosenescence in mice.

Aging is associated with a decrease in the function of the immune system, a phenomenon known as immunosenescence, which results in reduced resistance to infection. Caloric restriction (CR) is known to prolong lifespan and to regulate immune function. However, whether and how CR affects immunosenescence remains unclear. Here, we evaluated the effect of long- and short-term CR on immunosenescence by subjecting wild-type mice to CR between 6 and 18 months of age or between 17 and 18 months of age, respectively. Compared with a normal diet or short-term CR, long-term CR induced marked or complete attenuation of age-related decreases in the frequency of spleen NK cells and NKT cells; naïve CD4+ and CD8+ T cells; and cytokine- and granzyme B-secreting T cells. In contrast, both long- and short-term CR significantly suppressed age-related upregulation of the T cell exhaustion markers PD-1, Tim-3, and KLRG1, as well as the transcription factors NR4A1 and TOX, which regulate the expression of genes associated with the T cell exhaustion phenotype. These results suggest that CR might suppress age-associated immunosenescence by regulating the expression of transcription factors and target genes that control T cell exhaustion.

Resistance to Preoperative Oral Care Is Associated With Postoperative Pneumonia After Oesophageal Cancer Surgery.

BACKGROUND/AIM: Postoperative pneumonia is a serious complication of major oesophageal surgery. We aimed to clarify the association between the degree of improvement in oral hygiene by perioperative oral care and postoperative pneumonia in oesophageal cancer patients. PATIENTS AND METHODS: Oesophageal cancer patients (n=129) who underwent esophagectomy received perioperative oral care. Their oral hygiene was evaluated using the Oral Assessment Guide (OAG). The relationship between perioperative OAG scores and postoperative complications was analysed. RESULTS: The average OAG scores before starting oral care, pre-operation, and post-operation were 11.0±1.7, 9.1±1.5, and 11.2±3.0, respectively (p<0.001). An increase in preoperative OAG scores was independently associated with postoperative pneumonia on multivariate analysis (p=0.027). CONCLUSION: Preoperative oral care improves oral hygiene in patients undergoing oesophageal cancer surgery. No improvement in oral hygiene despite preoperative oral care was an independent predictor of postoperative pneumonia.

The suppression of IL-17 production from T cells by gallate-type procyanidin is mediated by selectively inhibiting cytokine production from dendritic cells.

Abnormal T helper 17 (Th17) responses promote inflammation and cause inflammatory diseases. Natural components that modulate Th17 functions can be effective for the amelioration of inflammatory diseases. Procyanidin B2 3,3''-di-O-gallate (PCB2DG) contained in grape seeds markedly suppressed interleukin (IL)-17 production from spleen cells but not CD4+ T cells. The aim of this study was to elucidate the mechanisms by which PCB2DG suppresses IL-17. Our results showed that PCB2DG suppressed the production of IL-17, tumor necrosis factor (TNF)-α, IL-1ß, and IL-6 with the suppression of transcription factors expression. In addition, we revealed that TNF-α and IL-1ß were required to induce IL-17 production in this experimental condition, and PCB2DG suppressed these cytokines from dendritic cells (DCs). Furthermore, CD4-DC co-culture experiments showed that the production of IL-17, TNF-α, and IL-1ß was markedly inhibited in co-cultures of PCB2DG-pretreated CD4+ T cells and DCs. These results suggested that PCB2DG first modulated TNF-α production by CD4+ T cells and then suppressed IL-1ß secretion from DCs, resulting in decreased IL-17 production. Thus, PCB2DG can control the cytokine network associated with Th17 cells, providing a novel mechanism underlying the immunosuppressive effects of polyphenols.

Predictive factors for dental inflammation with exacerbation during cancer therapy with FDG-PET/CT imaging.

PURPOSE: Oral adverse events, such as dental inflammation with exacerbation, are stressful and lead to poor nutrition in patients undergoing cancer therapy. Thus, the prediction of risk factors for dental inflammation with exacerbation is important before cancer therapy is initiated. We hypothesized that, during cancer therapy (DIECT), fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging could be useful to predict dental inflammation with exacerbation. METHODS: We enrolled 124 patients who underwent FDG-PET/CT for diagnostic staging before cancer treatment. We then assessed DIECT outcomes after basic perioperative oral treatment. Moreover, we evaluated clinical parameters, therapeutic strategies, periodontal examination (probing depth (PD) and bleeding on probing (BOP)), dental imaging, and FDG-PET/CT imaging results of patients with and without DIECT. Furthermore, PET/CT images were assessed as per the FDG accumulation of the dental lesion (PAD) grading system. RESULTS: Univariate analysis demonstrated significant differences in age, periodontal examination (PD and BOP), and PAD grade between patients with and without DIECT. Furthermore, multivariate logistic regression analysis identified independent predictive factors for a positive periodontal examination (PD) (odds ratio (OR) 5.9, 95% confidence interval (CI) 1.8-19.7; P = 0.004) and PAD grade (OR 11.6, 95% CI 3.2-41.2; P = 0.0002). In patients with cancer, PAD grade using FDG-PET/CT imaging was an independent and informative risk factor for DIECT. CONCLUSION: Our results suggested that, for patients with DIECT, periodontal examination and PAD grade were independent predictive factors. Hence, regardless of the presence or absence of any lesion on dental imaging, PAD grade might be an additional tool, in addition to periodontal examination that potentially improves oral care management.

Procyanidin B2 gallate regulates TNF-α production from T cells through inhibiting glycolytic activity via mTOR-HIF-1 pathway.

Procyanidins are polyphenols with antioxidant, anti-obesity, and anti-inflammatory properties. Procyanidin B2 (PCB2) gallate; specifically, PCB2 3,3″-di-O-gallate (PCB2DG), inhibits cytokine production in T cells. However, the molecular interactions and partners of PCB2DG underlying this suppression of cytokine production are unclear. The present study aimed to elucidate mechanisms underlying regulation of tumor necrosis factor (TNF)-α production by PCB2DG. We found that production of TNF-α and glycolytic activity in activated CD4+ T cells were suppressed by PCB2DG treatment. The inhibition of TNF-α production was found to be mediated by mammalian target of rapamycin (mTOR) and hypoxia inducible factor 1 (HIF-1) pathway, as PCB2DG suppressed the expression of HIF-1α, p-mTOR, and p-p70S6K (a downstream of the mTOR complex, mTORC1). Moreover, suppression of TNF-α production was mediated by regulation of the glycolytic enzyme lactate dehydrogenase at the posttranscriptional level. These results suggest that PCB2DG regulates TNF-α production by inhibiting glycolytic activity via the mTOR-HIF-1 pathway.

MicroRNA 16-5p is upregulated in calorie-restricted mice and modulates inflammatory cytokines of macrophages.

Caloric restriction (CR) has long been known to increase median and maximal lifespans and to decrease mortality and morbidity in short-lived animal models, likely by altering fundamental biological processes that regulate aging and longevity. However, the detailed mechanisms of immunomodulation by CR remain unclear. In this study, we established a mouse model for CR and analyzed the changes of immune cells in these mice. The CR mice fed a calorie-restricted diet for 4 weeks had lower body weight and fat mass compared with control mice. The proportions of CD4+, CD8+, and naïve CD4+ T cells in spleen cells from CR mice were higher than those in of control mice. Additionally, the proportion of CD8+ T cells was significantly decreased and the mRNA expression of proinflammatory cytokines in the colon of CR mice was significantly decreased compared with those of control mice. To determine the effect of CR on microRNA (miRNA) expression, serum and tissues were collected from mice and the expression level of miRNA was analyzed by real-time RT-PCR. As a result, the expressions of miR-16-5p, miR-196b-5p, and miR-218-5p in serum from CR mice were higher than those in control mice. The expression of miR-16-5p increased in the spleen, thymus, colon, and stomach of CR mice compared with expression in control mice. Furthermore, RAW264 cells transfected with a miR-16-5p mimic significantly decreased the mRNA expression of IL-1ß, IL-6, and TNF-α under LPS stimulation. These results suggested that miR-16-5p might be a critical factor involving the anti-inflammatory effects of calorie-restricted feeding.

Validity of using multi-frequency bioelectrical impedance analysis to measure skeletal muscle mass in preschool children.

[Purposes] Although it is recommended to develop a habit of physical activities, there is no easy way to measure skeletal muscle mass in preschool children, which cause the difficulty of evaluation. The purpose of this study was to examine the validity of body composition including the skeletal muscle mass assessment using multi-frequency bioelectrical impedance analysis by comparing body fat mass obtained by using multi-frequency bioelectrical impedance analysis method and body mass index formulas. [Subjects and Methods] Ninety-four children were surveyed for age, height, weight, grip strength, maximum occlusal force, thickness of muscle and fat mass (masseter and lower limb), body fat mass, skeletal muscle mass, and calf circumference. We assessed additional parameters, which were thought to be related to skeletal muscle mass, to ensure validity. [Results] A strong correlation was found in body fat mass values obtained using the multi-frequency bioelectrical impedance analysis method and those obtained using the body mass index formulas. Additionally, strong correlation coefficients were found between the skeletal muscle mass/height obtained using the multi-frequency bioelectrical impedance analysis method and grip strength and calf circumference. [Conclusion] Our results indicate that skeletal muscle mass can be reliably measured using the multi-frequency bioelectrical impedance analysis method in preschool children.