Reactive oxygen species and nuclear factor-kappa B pathway mediate high glucose-induced Pax-2 gene expression in mouse embryonic mesenchymal epithelial cells and kidney explants

Diabetic mellitus confers a major risk of congenital malformations, and is associated with diabetic embryopathy, affecting multiple organs including the kidney. The DNA paired box-2 (Pax-2) gene is essential in nephrogenesis. We investigated whether high glucose alters Pax-2 gene expression and aimed to delineate its underlying mechanism(s) of action using both in vitro (mouse embryonic mesenchymal epithelial cells (MK4) and ex vivo (kidney explant from Hoxb7-green florescent protein (GFP) mice) approaches. Pax-2 gene expression was determined by reverse transcriptase-polymerase chain reaction, Western blotting, and immunofluorescent staining. A fusion gene containing the full-length 5′-flanking region of the human Pax-2 promoter linked to a luciferase reporter gene, pGL-2/hPax-2, was transfected into MK4 cells with or without dominant negative IκBα (DN IκBα) cotransfection. Fusion gene expression level was quantified by cellular luciferase activity. Reactive oxygen species (ROS) generation was measured by lucigenin assay. Embryonic kidneys from Hoxb7-GFP mice were cultured ex vivo. High D(+) glucose (25mM), compared to normal glucose (5mM), specifically induced Pax-2 gene expression in MK4 cells and kidney explants. High glucose-induced Pax-2 gene expression is mediated, at least in part, via ROS generation and activation of the nuclear factor kappa B signaling pathway, but not via protein kinase C, p38 mitogen-activated protein kinase (MAPK), and p44/42 MAPK signaling

Proinflammatory Diets during Pregnancy and Neonatal Adiposity in the Healthy Start Study

Objective: To evaluate the association between dietary inflammatory index (DII) scores during pregnancy and neonatal adiposity. Study design: The analysis included 1078 mother–neonate pairs in Healthy Start, a prospective prebirth cohort. Diet was assessed using repeated 24-hour dietary recalls. DII scores were obtained by summing nutrient intakes, which were standardized to global means and multiplied by inflammatory effect scores. Air displacement plethysmography measured fat mass and fat-free mass within 72 hours of birth. Linear and logistic models evaluated the associations of DII scores with birth weight, fat mass, fat-free mass, and percent fat mass, and with categorical outcomes of small- and large-for-gestational age. We tested for interactions with prepregnancy BMI and gestational weight gain. Results: The interaction between prepregnancy BMI and DII was statistically significant for birth weight, neonatal fat mass, and neonatal percent fat mass. Among neonates born to obese women, each 1-unit increase in DII was associated with increased birth weight (53 g; 95% CI, 20, 87), fat mass (20 g; 95% CI, 7-33), and percent fat mass (0.5%; 95% CI, 0.2-0.8). No interaction was detected for small- and large-for-gestational age. Each 1-unit increase in DII score was associated a 40% increase in odds of a large-for-gestational age neonate (1.4; 95% CI, 1.0-2.0; P =.04), but not a small-for-gestational age neonate (1.0; 95% CI, 0.8-1.2; P =.80). There was no evidence of an interaction with gestational weight gain. Conclusions: Our findings support the hypothesis that an increased inflammatory milieu during pregnancy may be a risk factor for neonatal adiposity. Trial registration: Clinicaltrials.gov: NCT02273297

Dietary inflammatory potential, oxidative balance score, and risk of breast cancer: Findings from the Sister Study

Diet, inflammation, and oxidative stress may be important in breast carcinogenesis, but evidence on the role of the inflammatory and prooxidative potential of dietary patterns is limited. Energy adjusted-Dietary Inflammatory Index (E-DII™) and dietary oxidative balance score (D-OBS) were calculated for 43 563 Sister Study cohort participants who completed a Block 1998 food frequency questionnaire at enrollment in 2003–2009 and satisfied eligibility criteria. D-OBS was validated using measured F2-isoprostanes and metabolites. High E-DII score and low D-OBS represent a more proinflammatory and prooxidant diet, respectively, and associations of quartiles of each index with breast cancer (BC) risk were estimated using multivariable Cox proportional hazards regression. There were 2619 BCs diagnosed at least 1 year after enrollment (mean follow-up 8.4 years). There was no overall association between E-DII and BC risk, whereas there was a suggestive inverse association for the highest vs lowest quartile of D-OBS (HR 0.92 [95% CI, 0.81-1.03]). The highest quartile of E-DII was associated with risk of triple-negative BC (HR 1.53 [95% CI, 0.99-2.35]). When the two indices were combined, a proinflammatory/prooxidant diet (highest tertile of E-DII and lowest tertile of D-OBS) was associated with increased risk for all BC (HR 1.13 [95% CI, 1.00-1.27]) and for triple-negative BC (1.72 [95% CI, 1.10-2.70]), compared to an antiinflammatory/antioxidant diet (lowest tertile of E-DII and highest tertile of D-OBS). Diets with increased inflammatory potential and reduced oxidative balance were positively associated with overall and triple-negative BC

Proinflammatory diet is associated with increased risk of squamous cell head and neck cancer

Diets high in fruits and vegetables and low in red meat intake have been associated with decreased risk of head and neck cancer. Additionally, chronic inflammation pathways and their association with cancer have been widely described. We hypothesized a proinflammatory diet, as measured by the dietary inflammatory index (DII®), is associated with increased risk of head and neck cancer. We used the Carolina Head and Neck Cancer (CHANCE) study, a population-based case–control study of head and neck squamous cell carcinoma. Cases were recruited from a 46-county region in central North Carolina. Controls, frequency-matched on age, race, and sex were identified through the North Carolina Department of Motor Vehicle records. The DII score, adjusted for energy using the density approach (E-DII), was calculated from a food frequency questionnaire and split into four quartiles based on the distribution among controls. Adjusted odds ratios (ORs) were estimated with unconditional logistic regression. Cases had higher E-DII scores (i.e., a more proinflammatory diet) compared with controls (mean: −0.14 vs. −1.50; p value < 0.001). When compared with the lowest quartile, the OR for the highest quartile was 2.91 (95% confidence interval (CI): 2.16–3.95), followed by 1.93 (95% CI: 1.43–2.62) for the third quartile, and 1.37 (95% CI: 1.00–1.89) for the second quartile. Both alcohol and smoking had a significant additive interaction with E-DII (smoking relative excess risk due to interaction (RERI): 2.83; 95% CI: 1.36–4.30 and alcohol RERI: 1.75; 95% CI: 0.77–2.75). These results provide additional evidence for the association between proinflammatory diet and head and neck cancer

Stripes and holes in a two-dimensional model of spinless fermions and hardcore bosons

We consider a Hubbard-like model of strongly-interacting spinless fermions and hardcore bosons on a square lattice, such that nearest neighbor occupation is forbidden. Stripes (lines of holes across the lattice forming antiphase walls between ordered domains) are a favorable way to dope this system below half-filling. The problem of a single stripe can be mapped to a spin-1/2 chain, which allows understanding of its elementary excitations and calculation of the stripe's effective mass for transverse vibrations. Using Lanczos exact diagonalization, we investigate the excitation gap and dispersion of a hole on a stripe, and the interaction of two holes. We also study the interaction of two, three, and four stripes, finding that they repel, and the interaction energy decays with stripe separation as if they are hardcore particles moving in one (transverse) direction. To determine the stability of an array of stripes against phase separation into particle-rich phase and hole-rich liquid, we evaluate the liquid's equation of state, finding the stripe-array is not stable for bosons but is possibly stable for fermions.Comment: 24 pages, 18 figure

Maternal Diet Quality During Pregnancy and Offspring Hepatic Fat in Early Childhood: The Healthy Start Study

Background: Overnutrition in utero may increase offspring risk of nonalcoholic fatty liver disease (NAFLD), but the specific contribution of maternal diet quality during pregnancy to this association remains understudied in humans. Objectives: This study aimed to examine the associations of maternal diet quality during pregnancy with offspring hepatic fat in early childhood (median: 5 y old, range: 4–8 y old). Methods: Data were from 278 mother–child pairs in the longitudinal, Colorado-based Healthy Start Study. Multiple 24-h recalls were collected from mothers during pregnancy on a monthly basis (median: 3 recalls, range: 1–8 recalls starting after enrollment), and used to estimate maternal usual nutrient intakes and dietary pattern scores [Healthy Eating Index-2010 (HEI-2010), Dietary Inflammatory Index (DII), and Relative Mediterranean Diet Score (rMED)]. Offspring hepatic fat was measured in early childhood by MRI. Associations of maternal dietary predictors during pregnancy with offspring log-transformed hepatic fat were assessed using linear regression models adjusted for offspring demographics, maternal/perinatal confounders, and maternal total energy intake. Results: Higher maternal fiber intake and rMED scores during pregnancy were associated with lower offspring hepatic fat in early childhood in fully adjusted models [Back-transformed β (95% CI): 0.82 (0.72, 0.94) per 5 g/1000 kcal fiber; 0.93 (0.88, 0.99) per 1 SD for rMED]. In contrast, higher maternal total sugar and added sugar intakes, and DII scores were associated with higher offspring hepatic fat [Back-transformed β (95% CI): 1.18 (1.05, 1.32) per 5% kcal/d added sugar; 1.08 (0.99, 1.18) per 1 SD for DII]. Analyses of dietary pattern subcomponents also revealed that lower maternal intakes of green vegetables and legumes and higher intake of “empty calories” were associated with higher offspring hepatic fat in early childhood. Conclusions: Poorer maternal diet quality during pregnancy was associated with greater offspring susceptibility to hepatic fat in early childhood. Our findings provide insights into potential perinatal targets for the primordial prevention of pediatric NAFLD

A pro-inflammatory diet in people with multiple sclerosis is associated with an increased rate of relapse and increased FLAIR lesion volume on MRI in early multiple sclerosis: A prospective cohort study

First published online May 6, 2023Background: A pro-inflammatory diet has been posited to induce chronic inflammation within the central nervous system (CNS), and multiple sclerosis (MS) is an inflammatory disease of the CNS. Objective: We examined whether Dietary Inflammatory Index (DII®)) scores are associated with measures of MS progression and inflammatory activity. Methods: A cohort with a first clinical diagnosis of CNS demyelination was followed annually (10 years, n=223). At baseline, 5- and 10-year reviews, DII and energy-adjusted DII (E-DIITM) scores were calculated (food frequency questionnaire) and assessed as predictors of relapses, annualised change in disability (Expanded Disability Status Scale) and two magnetic resonance imaging measures; fluid-attenuated inversion recovery (FLAIR) lesion volume and black hole lesion volume. Results: A more pro-inflammatory diet was associated with a higher relapse risk (highest vs. lowest E-DII quartile: hazard ratio=2.24, 95% confidence interval (CI)= −1.16, 4.33, p=0.02). When we limited analyses to those assessed on the same manufacturer of scanner and those with a first demyelinating event at study entry (to reduce error and disease heterogeneity), an association between E-DII score and FLAIR lesion volume was evident (β=0.38, 95% CI=0.04, 0.72, p=0.03). Conclusion: There is a longitudinal association between a higher DII and a worsening in relapse rate and periventricular FLAIR lesion volume in people with MS.Alice M Saul, Bruce V Taylor, Leigh Blizzard, Steve Simpson-Yap, Wendy H Oddy, Nittin Shivappa, James R Hébert, Lucinda J Black, Anne-Louise Ponsonby, Simon A Broadley, Jeanette Lechner-Scott and Ingrid van der Mei, Ausimmune, AusLong Investigators Grou

Associations of maternal dietary inflammatory potential and quality with offspring birth outcomes: An individual participant data pooled analysis of 7 European cohorts in the ALPHABET consortium

BACKGROUND: Adverse birth outcomes are major causes of morbidity and mortality during childhood and associate with a higher risk of noncommunicable diseases in adult life. Maternal periconception and antenatal nutrition, mostly focusing on single nutrients or foods, has been shown to influence infant birth o

Association between dietary inflammatory index, and cause-specific mortality in the MONICA/KORA Augsburg Cohort Study.

Chronic diseases such as cancer and cardiovascular diseases (CVDs) are well-established causes of disability and premature death. Dietary components have been implicated in the etiology of these chronic diseases. We examined the ability of the Dietary Inflammatory Index (DIITM) to predict all-cause, coronary heart disease (CHD), CVD and cancer mortality and incident CHD in the MONICA-KORA Cohort Studies. DII scores were computed from baseline 7-day dietary records in this cohort of 1297 men, who were aged 45-64 years when enrolled. During the follow-up period, 551 total (155 CHD, 244 CVD and 175 cancer-related deaths) and 213 validated incident CHD events were identified through mortality record linkage and active follow-up. Spearman correlation coefficients were calculated between DII scores and the inflammatory marker C-reactive protein (CRP). Cox proportional hazards regression was used to estimate hazard ratios (HR) for the endpoints described above. DII scores were significantly positively correlated with CRP (P value < 0.0001). Positive associations were noted between DII and all-cause mortality (HRQ4vsQ1: 1.41; 95%CI 1.04-1.90;P-trend = 0.007) and incident CHD (HRQ4vsQ1: 1.83; 95%CI 1.12-3.01; P-trend = 0.008). These associations were attenuated after further adjustment for smoking status, but remained significant for all-cause mortality. When stratified by smoking status, DII was associated with all-cause and cancer mortality among ex-smokers, in the absence of significant heterogeneity. These results indicate that a pro-inflammatory diet as expressed by higher DII scores is associated with all-cause mortality. This association was more pronounced among ex-smokers in whom a significant association with cancer mortality was observed