Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth. Single injections of streptozotocin (40 mg/kg) or vehicle were used to induce hyperglycemia or normoglycemia, respectively, in female Wistar rats. After 3 days, rats were mated and pregnancy confirmed. Placental tissue was collected at 21 days of pregnancy. Placental expression of p65 subunit was similar between groups. However, nuclear translocation of p65 subunit, showing greater activation of NF-κB, was increased in the hyperglycemic group. Reduced expression of IκB and increased expression of phosphorylated IκB were observed in the placenta from hyperglycemic rats, demonstrating increased classical NF-κB activation. Augmented modification of O-GlcNAc-modified proteins was found in the placenta from hyperglycemic rats and p65 subunit was a key O-GlcNAc target, as demonstrated by immunoprecipitation. Tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expressions were increased in the placenta from hyperglycemic rats. Furthermore, placental weight was increased, whereas fetal weight was decreased under hyperglycemic conditions. TNF-α and IL-6 demonstrated positive correlations with placental weight and negative correlations with fetal weight and placental efficiency. Therefore, under hyperglycemic conditions, a modulatory role of O-GlcNAc in NF-κB activity was demonstrated in the placenta, contributing to fetal and placental dysfunction due to inflammatory cytokine exacerbation.

In this paper, $$f(R,T,R_{\mu \nu } T^{\mu \nu }$$ f ( R , T , R μ ν T μ ν ) gravity is considered. It is a modified theory of gravity that exhibits a strong coupling of gravitational and matter fields. Therefore, if gravity is governed by this model a number of issues must be re-examined. In this context, the question of causality and its violation is studied. Such analysis is carried out using the Gödel-type solutions. It is shown that this model allows both causal and non-causal solutions. These solutions depend directly on the content of matter present in the universe. For the non-causal solution, a critical radius is calculated, beyond which causality is violated. Taking different matter contents, an infinite critical radius emerges that leads to a causal solution. In this causal solution, a natural relationship emerges between the parameters that determine the matter considered.

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The Palatini [Formula: see text] gravity theory is considered. The standard Einstein–Hilbert action is replaced by an arbitrary function of the Ricci scalar [Formula: see text] and of the trace [Formula: see text] of the energy-momentum tensor. In the Palatini approach, the Ricci scalar is a function of the metric and the connection. These two quantities, metric and connection, are taken as independent variables. Then, it is examined whether Palatini [Formula: see text] gravity theory allows solutions in which lead to violation of causality. The Gödel and Gödel-type spacetimes are considered. In addition, a critical radius, which permits to examine limits for violation of causality, is calculated. It is shown that, for different matter contents, noncausal solutions can be avoided in this Palatini gravitational theory.

The [Formula: see text]-essence modified [Formula: see text] gravity model, i.e. [Formula: see text] theory is studied. The question of violation of causality, in the framework of Gödel-type universes, is investigated in this gravitational model. Causal and noncausal solutions are allowed. A critical radius for noncausal solution is calculated. It is shown that the violation of causality depends on the content of matter.