Head and neck cancer patients show poor oral health as compared to those with other types of cancer.

PURPOSE: Several studies have found associations between periodontitis and various types of cancer. Since the site of head and neck cancer (HNC) has contiguity or proximity to the oral cavity, it may be particularly influenced by oral inflammation. This study aimed to determine whether HNC patients have poor oral health as compared to those with other types of cancer. METHODS: This study retrospectively examined oral environmental factors including periodontal inflamed surface area (PISA), a new periodontal inflammatory parameter. A total of 1030 cancer patients were divided into the HNC (n = 142) and other cancer (n = 888) groups. Furthermore, the HNC group was divided into high (n = 71) and low (n = 71) PISA subgroups, and independent risk factors affecting a high PISA value were investigated. RESULTS: Multivariate logistic regression analysis showed that number of missing teeth (odds ratio 1.72, 95% CI 1.15-2.56, P < 0.01), PISA (odds ratio 1.06, 95% CI 1.03-1.06, P < 0.05), and oral bacterial count (odds ratio 1.02, 95% CI 1.01-1.03, P < 0.01) were independent factors related to HNC. In addition, multivariate logistic regression analysis indicated that current smoker (odds ratio 7.51, 95% CI 1.63-34.71, P < 0.01) and presence of untreated dental caries (odds ratio 3.33, 95% CI 1.23-9.00, P < 0.05) were independent risk factors affecting high PISA values in HNC patients. CONCLUSION: HNC patients have higher levels of gingival inflammation and poor oral health as compared to patients with other types of cancer, indicating that prompt oral assessment and an effective oral hygiene management plan are needed at the time of HNC diagnosis.

Oleic acid to stearic acid ratio might be a potential marker for insulin resistance in non-obese Japanese.

Results from a recent study indicate that a higher level of oleic acid/stearic acid ratio was associated with metabolically unhealthy obesity. This was further validated in cross-sectional and interventional studies; however, this was not extensively studied in a non-obese population. We recruited 260 Japanese subjects with serum free fatty acid profiles undergoing anti-aging health examinations. The determinants for oleic acid/stearic acid ratio were investigated using multiple regression analyses. To compare different markers, the subjects were classified based on oleic acid/stearic acid ratio and the combination of oleic acid/stearic acid ratio and triglyceride levels. The oleic acid/stearic acid ratio exhibited a positive correlation with the logmatic transformed triglyceride/high-density lipoprotein cholesterol ratio and the fasting triglycerides-glucose index, both of which were used as markers for insulin resistance. Multiple regression analyses revealed that the triglyceride/high-density lipoprotein cholesterol ratio and fasting triglyceride-glucose index were positively associated with the oleic acid/stearic acid ratio. Most markers were the worst in the highest triglyceride group in both oleic acid/stearic acid groups. In addition, most markers were worse in high oleic acid/stearic acid ratio group than low group. In conclusion, oleic acid/stearic acid ratio might be a useful marker for insulin resistance in non-obese Japanese subjects.

Usefulness of Triglyceride to High-Density Lipoprotein Ratio and Alanine Aminotransferase for Predicting Insulin Resistance and Metabolic Syndrome in the Japanese Population.

Background: Considering the fact that both alanine aminotransferase (ALT) and the triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio are useful markers for cardiovascular disease, insulin resistance (IR), and metabolic syndrome (MetS), the possible association of ALT and TG/HDL-C ratio is conceivable, but the association is not well studied. Moreover, assessment of IR and MetS by a combination lipid and liver biomarkers has rarely been carried out. Methods: A total of 11,808 Japanese subjects who underwent an annual health examination and who were not taking medications were recruited. The association between TG/HDL-C ratio and ALT level was investigated using correlation and multiple linear regression analyses. Homeostasis model assessment of insulin resistance (HOMA-IR) and the number of MetS components were evaluated after subjects were stratified by TG/HDL-C ratio and ALT levels. Results: Correlation analysis revealed that ALT levels were positively associated with TG/HDL-C ratio. Moreover, multiple linear regression analysis revealed that TG/HDL-C ratio was positively associated with ALT levels, and the association was attenuated but persisted in both men and women after additional adjustment for visceral adiposity (body mass index, waist circumference, or fatty liver) and IR (HOMA-IR). HOMA-IR and MetS component number increased with either ALT or TG/HDL-C ratio in both men and women. HOMA-IR and MetS component number were particularly high (HOMA-IR: men 2.82, women 3.22, MetS component number: men 2.6, women 2.1) in subjects with highest ALT level and TG/HDL-C ratio. Conclusions: TG/HDL-C ratio showed a positive association with ALT levels in both sexes. Assessments of IR and MetS can become more precise by evaluating TG/HDL-C ratio and ALT, simultaneously.

Uric acid, ferritin and γ-glutamyltransferase can be informative in prediction of the oxidative stress.

The anti-oxidant system is affected not only by aging but also many lifestyle factors. We aimed to clarify the determinants of medical check-up items affecting the anti-oxidant system. We studied 959 Japanese individuals who underwent anti-aging health check-ups (mean age: 61.1 years) at Tokai University from 2006 to 2016. As parameters of oxidative stress, we measured serum total anti-oxidant status, 8-hydroxy-2'-deoxyguanosine, and isoprostane. Anti-aging health check-up data and lifestyle information were collected from participants in this study. Step-wise multiple regression analyses were conducted to identify determinants that influence serum total anti-oxidant status, 8-hydroxy-2'-deoxyguanosine, and isoprostane, respectively. Serum total anti-oxidant status was significantly correlated with uric acid, vitamin A, folate, and valine. 8-hydroxy-2'-deoxyguanosine was significantly correlated with age, ferritin, drinking habit, and vitamin Eα. Isoprostane was significantly correlated with vitamin Eα, γ-glutamyltransferase, ferritin, and smoking habit. The strong antioxidant powers of uric acid and vitamins were confirmed. It was suggested that branched-chain amino acids themselves such as valine or peptides containing them may possess antioxidant ability because of its strong correlation. Uric acid, ferritin, and γ-glutamyltransferase, which are common items measured in medical checkups, can be informative in predicting the oxidative stress situation in a general medical examination.

Serum interleukin-18 levels are associated with physical activity in Japanese men.

OBJECTIVE: To investigate the link between serum interleukin-18 (IL-18) levels and physical activity in Japanese men. METHODS: A total of 81 men (45.7±17.6 years old) was enrolled in this cross-sectional investigation study. We assessed anthropometric and body composition parameters. Serum IL-18 levels, physical activity by uniaxial accelerometers, peak oxygen uptake and metabolic risk parameters were also evaluated. RESULTS: Serum IL-18 levels were 179.4±84.7 pg/mL. Physical activity evaluated by Σ[metabolic equivalents × h per week (METs⋅h/w)]was significantly and negatively correlated with serum IL-18 levels (r = -0.252, p = 0.0235). These associations remained even after adjusting for age, peak oxygen uptake and other confounding factors. CONCLUSION: Serum IL-18 levels were closely associated with physical activity independent of peak oxygen uptake in Japanese men.

Relationship between cigarette smoking and muscle strength in Japanese men.

OBJECTIVES: To investigate the link between cigarette smoking and muscle strength in Japanese men. METHODS: We used data on 4249 Japanese men, aged 43.3±13.9 years, in this cross-sectional investigation study. Grip strength and leg strength were measured as indicators of overall muscle strength. Meanwhile, subjects' cigarette smoking habits were recorded by trained medical staff. The effect of cigarette smoking on muscle strength was evaluated. RESULTS: A total of 1618 men (38.1%) were smokers and 1481 men (34.9%) exercised regularly. Significant differences in muscle strength were noted between men with and without a Brinkman index of 400 or greater, after adjusting for age. After adjusting for age, height, body weight and exercise habits, associations between the Brinkman index and leg strength and the ratio of leg strength to body weight were attenuated. CONCLUSIONS: Cigarette smoking might be negatively associated with muscle strength, especially grip strength in Japanese men.

Smoking confers a MTHFR 677C>T genotype-dependent risk for systemic atherosclerosis: results from a large number of elderly autopsy cases that died in a community-based general geriatric hospital.

AIM: We attempted to explore interactions between smoking and the genetic polymorphism of 24 atherosclerosis-related candidate genes in systemic atherosclerosis. METHODS: The study comprised 1,503 consecutive autopsy cases. The male-to-female ratio was 1.16 and the average age at death was 80.3 years. Seventy percent of men and 22% of women were current or past smokers. The degree of atherosclerosis in 10 arteries was semi-quantitatively assessed. Melting curve analysis analyzed 34 single nucleotide polymorphisms (SNPs) of 24 genes. RESULTS: Twenty-four SNPs did not interact with smoking on atherosclerosis, while 7 SNPs interacted in one artery and 2 SNPs in two arteries. The genotypes of MTHFR 677C>T and smoking significantly interacted in four arteries, including the common carotid artery, common and external iliac arteries, and femoral artery. The odds ratios of smoking on atherosclerosis were high (3.034.63) in TT homozygotes, intermediate (1.755.24) in heterozygotes, and low (1.752.63) in CC homozygotes in systemic arteries except for cerebral and coronary arteries. CONCLUSION: MTHFR 677 TT homozygotes are more likely to develop atherosclerosis than heterozygotes or CC homozygotes, if they smoke. Thus, smoking cessation is more important in the prevention of atherosclerosis in MTHFR 677 TT homozygotes.

New challenges for text mining: mapping between text and manually curated pathways.

BACKGROUND: Associating literature with pathways poses new challenges to the Text Mining (TM) community. There are three main challenges to this task: (1) the identification of the mapping position of a specific entity or reaction in a given pathway, (2) the recognition of the causal relationships among multiple reactions, and (3) the formulation and implementation of required inferences based on biological domain knowledge. RESULTS: To address these challenges, we constructed new resources to link the text with a model pathway; they are: the GENIA pathway corpus with event annotation and NF-kB pathway. Through their detailed analysis, we address the untapped resource, 'bio-inference,' as well as the differences between text and pathway representation. Here, we show the precise comparisons of their representations and the nine classes of 'bio-inference' schemes observed in the pathway corpus. CONCLUSIONS: We believe that the creation of such rich resources and their detailed analysis is the significant first step for accelerating the research of the automatic construction of pathway from text.

Structural analysis of the fundamental polymer of the sheath constructed by Sphaerotilus natans.

The sheath of Sphaerotilus natans is composed of cysteine-rich peptide and polysaccharide moieties. The polysaccharide was prepared by treating the sheath with hydrazine, and was determined to be a mucopolysaccharide containing beta-D-GlcA, beta-D-Glc, alpha-D-GalN, and beta-D-GalN. To elucidate the structure of the peptide, the sheath was labeled with a thiol-selective fluorogenic reagent, 4-(aminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole. Enantiomeric determination of the S-derivatized Cys in the fluorescent sheath suggested that it contained L-Cys mainly. Fluorescent cysteinylglycine was detected in the partial acid hydrolysate of the fluorescent sheath. The sheath-degrading enzyme secreted by Paenibacillus koleovorans produced a fluorescent disaccharide-dipeptide composed of GalN, Gly, and N-acetylated Cys from the fluorescent sheath. The disaccharide and dipeptide moieties were found to be connected by an amide bond. Based on these results, the sheath was deduced to be formed by association of a mucopolysaccharide modified with N-acetyl-L-cysteinylglycine.

Polymorphisms in pro- and anti-inflammatory cytokine genes and susceptibility to atherosclerosis: a pathological study of 1503 consecutive autopsy cases.

Atherosclerosis is a chronic inflammatory disease in the intima of the arterial wall, where cytokines play a crucial role in the pathogenesis of this disease. However, the question of whether or not genetic variations in the cytokine genes could influence the development of atherosclerosis has been poorly investigated. We investigated the relationship of nine common single-nucleotide polymorphisms (SNPs) in tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-10, IL-4 and transforming growth factor (TGF)-beta1 with the atherosclerotic severity in 10 different arteries based on 1503 consecutive autopsies of elderly Japanese subjects registered in the Japanese SNPs for geriatric research (JG-SNP) study. The -1031C allele of TNF-alpha was a significant protective factor for atherogenesis in the carotid, femoral and intracranial arteries [odds ratio (OR): 0.72, 0.73 and 0.70, respectively]. The -511T of IL-1beta and the +29T of TGF-beta1 were significant risk factors for atherogenesis in the subclavian and intracranial arteries (OR: 1.35 and 1.48, respectively). In contrast, conventional risk factors for atherogenesis, such as hypertension and diabetes mellitus, conferred independent risks for almost all arteries. Functional SNPs in TNF-alpha, IL-1beta and TGF-beta1 genes play a role in atherogenesis, although their influences are less pronounced than those of conventional risk factors and appear to be limited to specific arteries in the Japanese elderly.

Robustness trade-offs and host-microbial symbiosis in the immune system.

The immune system provides organisms with robustness against pathogen threats, yet it also often adversely affects the organism as in autoimmune diseases. Recently, the molecular interactions involved in the immune system have been uncovered. At the same time, the role of the bacterial flora and its interactions with the host immune system have been identified. In this article, we try to reconcile these findings to draw a consistent picture of the host defense system. Specifically, we first argue that the network of molecular interactions involved in immune functions has a bow-tie architecture that entails inherent trade-offs among robustness, fragility, resource limitation, and performance. Second, we discuss the possibility that commensal bacteria and the host immune system constitute an integrated defense system. This symbiotic association has evolved to optimize its robustness against pathogen attacks and nutrient perturbations by harboring a broad range of microorganisms. Owing to the inherent propensity of a host immune system toward hyperactivity, maintenance of bacterial flora homeostasis might be particularly important in the development of preventive strategies against immune disorders such as autoimmune diseases.

A comprehensive map of the toll-like receptor signaling network.

Recognition of pathogen-associated molecular signatures is critically important in proper activation of the immune system. The toll-like receptor (TLR) signaling network is responsible for innate immune response. In mammalians, there are 11 TLRs that recognize a variety of ligands from pathogens to trigger immunological responses. In this paper, we present a comprehensive map of TLRs and interleukin 1 receptor signaling networks based on papers published so far. The map illustrates the possible existence of a main network subsystem that has a bow-tie structure in which myeloid differentiation primary response gene 88 (MyD88) is a nonredundant core element, two collateral subsystems with small GTPase and phosphatidylinositol signaling, and MyD88-independent pathway. There is extensive crosstalk between the main bow-tie network and subsystems, as well as feedback and feedforward controls. One obvious feature of this network is the fragility against removal of the nonredundant core element, which is MyD88, and involvement of collateral subsystems for generating different reactions and gene expressions for different stimuli.

Using process diagrams for the graphical representation of biological networks.

With the increased interest in understanding biological networks, such as protein-protein interaction networks and gene regulatory networks, methods for representing and communicating such networks in both human- and machine-readable form have become increasingly important. Although there has been significant progress in machine-readable representation of networks, as exemplified by the Systems Biology Mark-up Language (SBML) (http://www.sbml.org) issues in human-readable representation have been largely ignored. This article discusses human-readable diagrammatic representations and proposes a set of notations that enhances the formality and richness of the information represented. The process diagram is a fully state transition-based diagram that can be translated into machine-readable forms such as SBML in a straightforward way. It is supported by CellDesigner, a diagrammatic network editing software (http://www.celldesigner.org/), and has been used to represent a variety of networks of various sizes (from only a few components to several hundred components).

A comprehensive pathway map of epidermal growth factor receptor signaling.

The epidermal growth factor receptor (EGFR) signaling pathway is one of the most important pathways that regulate growth, survival, proliferation, and differentiation in mammalian cells. Reflecting this importance, it is one of the best-investigated signaling systems, both experimentally and computationally, and several computational models have been developed for dynamic analysis. A map of molecular interactions of the EGFR signaling system is a valuable resource for research in this area. In this paper, we present a comprehensive pathway map of EGFR signaling and other related pathways. The map reveals that the overall architecture of the pathway is a bow-tie (or hourglass) structure with several feedback loops. The map is created using CellDesigner software that enables us to graphically represent interactions using a well-defined and consistent graphical notation, and to store it in Systems Biology Markup Language (SBML).

Metabolic syndrome and robustness tradeoffs.

The metabolic syndrome is a highly complex breakdown of normal physiology characterized by obesity, insulin resistance, hyperlipidemia, and hypertension. Type 2 diabetes is a major manifestation of this syndrome, although increased risk for cardiovascular disease (CVD) often precedes the onset of frank clinical diabetes. Prevention and cure for this disease constellation is of major importance to world health. Because the metabolic syndrome affects multiple interacting organ systems (i.e., it is a systemic disease), a systems-level analysis of disease evolution is essential for both complete elucidation of its pathophysiology and improved approaches to therapy. The goal of this review is to provide a perspective on systems-level approaches to metabolic syndrome, with particular emphasis on type 2 diabetes. We consider that metabolic syndromes take over inherent dynamics of our body that ensure robustness against unstable food supply and pathogenic infections, and lead to chronic inflammation that ultimately results in CVD. This exemplifies how trade-offs between robustness against common perturbations (unstable food and infections) and fragility against unusual perturbations (high-energy content foods and low-energy utilization lifestyle) is exploited to form chronic diseases. Possible therapeutic approaches that target fragility of emergent robustness of the disease state have been discussed. A detailed molecular interaction map for adipocyte, hepatocyte, skeletal muscle cell, and pancreatic beta-cell cross-talk in the metabolic syndrome can be viewed at http://www.systems-biology.org/001/003.html.