Links between oral microbiome and insulin resistance: Involvement of MAP kinase signaling pathway.

Oral dysbiosis contributes to periodontitis and has implications for systemic diseases. Diabetes mellitus is a common metabolic disorder characterized by impaired glucose regulation. AMP-activated protein kinase (AMPK) plays a vital role in regulating glucose uptake and glycogenesis in the liver. This study aimed to investigate the association between periodontal bacteria and diabetes mellitus. A clinical trial was conducted to explore the association between oral bacteria and hyperglycemia. Additionally, we elucidated the molecular mechanisms by which periodontal bacteria cause insulin resistance. In the clinical trial, we discovered significant alterations in the expression levels of Fusobacterium nucleatum (Fn) and Tannerella forsythia (Tf) in patients with diabetes compared with healthy controls. Furthermore, Fn and Tf levels positively correlated with fasting blood glucose and glycated hemoglobin (HbA1C) levels. Moreover, we explored and elucidated the molecular mechanism by which Fusobacterium nucleatum culture filtrate (FNCF) induces cytokine release via the Toll-like receptor 2 (TLR2) signaling pathway in human gingival epithelial Smulow-Glickman (S-G) cells. This study investigated the effects of cytokines on insulin resistance pathways in liver cells. The use of an extracellular signal-regulated kinase (ERK) inhibitor (U0126) demonstrated that FNCF regulates the insulin receptor substrate 1 and protein kinase B (IRS1/AKT) signaling pathway, which affects key proteins involved in hepatic glycogen synthesis, including glycogen synthase kinase-3 beta (GSK3ß) and glycogen synthase (GS), ultimately leading to insulin resistance. These findings suggest that ERK plays a crucial role in hepatocyte insulin resistance.

Identification of hyperglycemia-associated microbiota alterations in saliva and gingival sulcus.

Oral microbes are a contributing factor to hyperglycemia by inducing an increase in insulin resistance resulting in uncontrolled blood glucose levels. However, the relationship between the distribution of oral flora and hyperglycemia is still controversial. Combining the power of MALDI-Biotyper with anaerobic bacterial culture, this study explores the correlation between anaerobic bacteria in the oral cavity and blood glucose levels. The results demonstrated that altered blood glucose levels contributed to a varied bacterial distribution in the oral cavity. Specifically, Veillonella spp. and Prevotella spp. were identified in a higher proportion in people with elevated blood glucose levels. Six bacterial species identified in this study (Prevotella melaninogenica, Campylobacter rectus, Streptococcus gordonii, Streptococcus mitis, Streptococcus salivarius, and Veillonella parvula) not only demonstrated a positive association with higher blood glucose levels, but also likely contribute to the development of the condition. The data demonstrated MALDI-TOF MS to be a simpler, faster, and more economical clinical identification tool that provides clarity and depth to the research on blood glucose and oral microbiota.

Construction of gene causal regulatory networks using microarray data with the coefficient of intrinsic dependence.

BACKGROUND: In the past two decades, biologists have been able to identify the gene signatures associated with various phenotypes through the monitoring of gene expressions with high-throughput biotechnologies. These gene signatures have in turn been successfully applied to drug development, disease prevention, crop improvement, etc. However, ignoring the interactions among genes has weakened the predictive power of gene signatures in practical applications. Gene regulatory networks, in which genes are represented by nodes and the associations between genes are represented by edges, are typically constructed to analyze and visualize such gene interactions. More specifically, the present study sought to measure gene-gene associations by using the coefficient of intrinsic dependence (CID) to capture more nonlinear as well as cause-effect gene relationships. RESULTS: A stepwise procedure using the CID along with the partial coefficient of intrinsic dependence (pCID) was demonstrated for the rebuilding of simulated networks and the well-known CBF-COR pathway under cold stress using Arabidopsis microarray data. The procedure was also applied to the construction of bHLH gene regulatory pathways under abiotic stresses using rice microarray data, in which OsbHLH104, a putative phytochrome-interacting factor (OsPIF14), and OsbHLH060, a positive regulator of iron homeostasis (OsPRI1) were inferred as the most affiliated genes. The inferred regulatory pathways were verified through literature reviews. CONCLUSIONS: The proposed method can efficiently decipher gene regulatory pathways and may assist in achieving higher predictive power in practical applications. The lack of any mention in the literature of some of the regulatory event may have been due to the high complexity of the regulatory systems in the plant transcription, a possibility which could potentially be confirmed in the near future given ongoing rapid developments in bio-technology.

Difference between observed and predicted glycated hemoglobin at baseline and treatment response to vildagliptin-based dual oral therapy in patients with type 2 diabetes.

AIM: We aimed to investigate the association of difference between observed and predicted glycated hemoglobin (dopHbA1c) and HbA1c reduction after vildagliptin-based oral therapy in patients with type 2 diabetes (T2D). METHODS: This was a prospective observational study. Adults ≥ 20 years old with T2D and HbA1c ≧7% treated with oral anti-diabetic drugs (OADs) were eligible if their OADs were shifted to vildagliptin-based dual oral therapy. Fasting plasma glucose (FPG) and HbA1c were recorded at baseline, week 12, and week 24. To determine baseline dopHbA1c, a predicted HbA1c was calculated by inserting baseline FPG into a regression equation (HbA1c = FPG ∗ 0.0225 + 4.3806) developed from linear relationship between HbA1c and FPG in an independent cohort of 3239 outpatients with T2D (dopHbA1c = observed HbA1c - predicted HbA1c). Patients were assigned to low (≦0) or high (>0) dopHbA1c group according to their baseline dopHbA1c levels. The study endpoint was changes from baseline to week 24 in HbA1c levels. RESULTS: A total of 1224 patients were enrolled. Patients with a dopHbA1c >0 had a greater HbA1c reduction after vildagliptin-based dual oral therapy than those with a dopHbA1c ≦0 (-1.5 ±â€¯2.0 vs. -0.4 ±â€¯1.0%, p < 0.001). Baseline dopHbA1c was positively associated with HbA1c reduction from baseline to week 24 (ß coefficient 0.883, 95% CI 0.811 to 0.955, p < 0.001), and the association remained significant after adjustment for confounders. CONCLUSIONS: In T2D patients with an HbA1c ≧7%, a higher baseline dopHbA1c was associated with a greater HbA1c reduction after shifting to vildagliptin-based dual oral therapy.

A Stepwise Approach of Finding Dependent Variables via Coefficient of Intrinsic Dependence.

The coefficient of intrinsic dependence (CID) is capable of determining associations among variables without making distributional or functional assumptions regarding random variables. In this study, we developed the partial coefficient of intrinsic dependence (pCID) to facilitate the step-by-step selection of variables that are relevant to a target variable. The strategy of selecting relevant variables using the CID along with the pCID can eliminate interference from other relevant variables. From simulation results, we observed that the proposed method is more sensitive to curvilinearity and more specific to linearity than the combination of Pearsons correlation coefficient and the partial correlation coefficient (PCC/pPCC). This property may provide the opportunity to index different levels of curvilinearity according to CID/pCID outcomes. In practice trials conducted using publicly available microarray data, the CID/pCID procedure successfully identified cold-responsive genes related to three C-repeat binding factors, and was especially effective at identifying some sample-specific gene-gene interactions. Therefore, the proposed strategy may be beneficial in meta-analysis to distinguish general forms of relationships from the noise.

Prevalence of Helicobacter pylori infection in high-school students on Lanyu Island, Taiwan: risk factor analysis and effect on growth.

BACKGROUND/PURPOSE: The Yami inhabit Lanyu Island and are the smallest and most primitive aboriginal tribe in Taiwan. Lanyu Island is a closed environment and little information is available on the prevalence of Helicobacter pylori infection there. This study aimed to establish the prevalence of H. pylori infection in high-school students on Lanyu Island and its risk factors and effect on growth. METHODS: A cross-sectional population-based study was conducted among high-school students to determine the prevalence of H. pylori infection by using the 13C urea breath test. A questionnaire was administered to the recruited population. Relevant personal and socioeconomic data for risk factors of infection were collected. Body height and weight of the recruited adolescents in relation to H. pylori infection were analyzed. RESULTS: A total of 106 high-school students (55 boys and 51 girls), with a mean age of 14.3 +/- 1.4 years were enrolled. The overall prevalence of H. pylori infection was 54.7%. Those residing in Dongcing village had the highest rate of H. pylori infection (73.3%). There was no difference in the prevalence of H. pylori infection according to sex, ethnicity, socioeconomic level or parental education. Sixty-two students (54.8%) were completely asymptomatic and the others had at least one gastrointestinal symptom. H. pylori infection was asymptomatic in 56.8% and symptomatic in 53.2% of students. There was no significant difference between infected and uninfected children with regard to body weight, height and body mass index. CONCLUSION: The prevalence of H. pylori infection is high among high-school students on Lanyu Island. There is no evidence that infection is related to growth failure.

Necrotizing fasciitis in southeast Taiwan: clinical features, microbiology, and prognosis.

OBJECTIVES: To determine the spectrum of microorganisms, clinical features, and risk factors of necrotizing fasciitis in southeast Taiwan. METHODS: We retrospectively studied patients diagnosed with necrotizing fasciitis and fully treated in our hospital for the period January 1995 to December 2006. RESULTS: The mean age of the patients was 58.2+/-14.2 years. The affected anatomical sites were primarily peripheral (91 patients, 85.8%). Sixty patients (56.6%) had a type 1 infection, 17 patients (16.0%) had type 2, and eight patients (7.5%) had type 3. Diabetes mellitus was the most common comorbidity. A single pathogen was identified as the infectious agent in 64 patients (60.4%), multiple pathogens were identified in 21 patients (19.8%), and no organism was identified in 21 patients (19.8%). Streptococcus pyogenes was the most common pathogen. The average hospital stay was 28.0+/-23.1 days. Patients received a mean of 2.3+/-1.2 debridements, and five patients (4.7%) eventually underwent an amputation. The overall mortality was 17.0%. Predictors of mortality included advanced age, class C liver cirrhosis, ascites, higher serum creatinine, and lower hemoglobin and platelet levels. CONCLUSIONS: Monobacterial infections are more common in our patients. Accurate early diagnosis and extensive surgical debridement are essential for a favorable outcome.

Formative research for a healthy diet intervention among inner-city adolescents: the importance of family, school and neighborhood environment.

OBJECTIVES: To understand influences on diet among low-income African-American adolescents in East Baltimore. METHODS: Formative research was conducted for a food store-centered healthy diet intervention targeted to inner-city youth. Family, school and neighborhood influences on eating habits and health concepts were explored. RESULTS: Family structure, economic resources and past experiences influence what food means to adolescents. Healthy food in school and local stores is limited. Terminology to categorize foods was identified, including the term "home foods". CONCLUSIONS: Suggested adolescent nutritional interventions include promotion of home-based eating, improving availability of healthy foods in school and neighborhood stores, and targeted educational materials.