RETRACTED: Serebrovska et al. Intermittent Hypoxia-Hyperoxia Training Improves Cognitive Function and Decreases Circulating Biomarkers of Alzheimer's Disease in Patients with Mild Cognitive Impairment: A Pilot Study. Int. J. Mol. Sci. 2019, 20, 5405.

The journal Int [...].

SINGLE NUCLEOTIDE POLYMORPHISM RS4696480 OF TLR2 GENE ASSOCIATES WITH SEVERITY OF ATOPIC DERMATITIS IN CHILDREN, BUT NOT WITH IGE SENSITIZATION TO MALASSEZIA.

OBJECTIVE: The aim: Malassezia has been linked to atopic dermatitis, and TLRs are suggested to mediate influence of Malassezia spp on human cells. The aim of the study was to examine if TLR2 rs4696480 polymorphism predisposes to atopic dermatitis, IgE sensitization to Malassezia or to severe phenotype of atopic dermatitis. PATIENTS AND METHODS: Materials and methods: The study included 103 patients with eczema and 84 healthy children. Specific IgE against Malassezia mix (m227) was analyzed in 47 patients using immunochemiluminescent method on the ImmunoCAP 100 (Thermo Fisher Scientific Inc., Phadia, Sweden). Genotyping for TLR2 rs4696480 was performed by using Real-time PCR. RESULTS: Results: Increased IgE to Malassezia spp. was observed in 34,3 % of children with eczema. Higher Malassezia spp.-specific IgE titre positively correlated with duration of atopic dermatitis and a higher total IgE. There were no difference in allele distribution among patients and control group (OR=1.096 (0.549- 2.191) for AT, OR=0.946 (0.430- 2.078) for TT, р > 0,05). TLR2 polymorphism rs4696480 was not associated with Malassezia spp.-sIgE. AA-genotype was significantly more frequent among patients with severe and moderate-to-severe AD (OR=6.395 (1.240-32.991). CONCLUSION: Conclusions: AA variant of TLR2 rs4696480 polymorphism predisposes to severe phenotype of AD.

Cholesterol enriched diet suppresses ATF6 and PERK and upregulates the IRE1 pathways of the unfolded protein response in spontaneously hypertensive rats: Relevance to pathophysiology of atherosclerosis in the setting of hypertension.

Many studies have been dedicated to hypertension and hypercholesterolemia, as they are the primary conditions that influence the unfolded protein response (UPR). However, the concurrent effects of these two factors are unknown. Our research used spontaneously hypertensive rats (SHR) fed a cholesterol enriched diet (CED) as model of atherosclerosis formation to discover what effect the simultaneous actions of hypertension and hypercholesterolemia have on the UPR. The combination of hypertension and consumption of a CED (not the CED alone) caused the formation of early atherosclerotic features. Both increased expression of the CCAAT-enhancer-binding protein (CHOP) and the insulin induced gene 1 (INSIG1), which is the target gene of the sterol regulatory element-binding protein 1-c (SREBP1-c), and decreased expression of the spliced x-box binding protein1 (sXBP1) mRNA were observed in the SHR fed a CED. Cholesterol overload strongly suppressed glucose regulated protein 78 (GRP78), glucose regulated protein 94 (GRP 94), and the expression of CHOP and INSIG1 mRNA in both normotensive and hypertensive rats. Unlike other UPR factors, the sXBP1 mRNA expression was strongly downregulated in SHR fed a normal diet but upregulated in those fed a CED. The changes to UPR in the SHR fed a CED were associated with improvement of the initially impaired heart function of the rats.

Intermittent Hypoxia-Hyperoxia Training Improves Cognitive Function and Decreases Circulating Biomarkers of Alzheimer's Disease in Patients with Mild Cognitive Impairment: A Pilot Study.

Alzheimer's disease (AD) affects not only the central nervous system, but also peripheral blood cells including neutrophils and platelets, which actively participate in pathogenesis of AD through a vicious cycle between platelets aggregation and production of excessive amyloid beta (Aß). Platelets adhesion on amyloid plaques also increases the risk of cerebral microcirculation disorders. Moreover, activated platelets release soluble adhesion molecules that cause migration, adhesion/activation of neutrophils and formation of neutrophil extracellular traps (NETs), which may damage blood brain barrier and destroy brain parenchyma. The present study examined the effects of intermittent hypoxic-hyperoxic training (IHHT) on elderly patients with mild cognitive impairment (MCI), a precursor of AD. Twenty-one participants (age 51-74 years) were divided into three groups: Healthy Control (n = 7), MCI+Sham (n = 6), and MCI+IHHT (n = 8). IHHT was carried out five times per week for three weeks (total 15 sessions). Each IHHT session consisted of four cycles of 5-min hypoxia (12% FIO2) and 3-min hyperoxia (33% FIO2). Cognitive parameters, Aß and amyloid precursor protein (APP) expression, microRNA 29, and long non-coding RNA in isolated platelets as well as NETs in peripheral blood were investigated. We found an initial decline in cognitive function indices in both MCI+Sham and MCI+IHHT groups and significant correlations between cognitive test scores and the levels of circulating biomarkers of AD. Whereas sham training led to no change in these parameters, IHHT resulted in the improvement in cognitive test scores, along with significant increase in APP ratio and decrease in Aß expression and NETs formation one day after the end of three-week IHHT. Such effects on Aß expression and NETs formation remained more pronounced one month after IHHT. In conclusion, our results from this pilot study suggested a potential utility of IHHT as a new non-pharmacological therapy to improve cognitive function in pre-AD patients and slow down the development of AD.

Correction to: Cardiospecific deletion of αE-catenin leads to heart failure and lethality in mice.

The original version of this article unfortunately contained a mistake. The published paper presented an incorrect version of Table 1. The corrected Table is given here.

Cardiospecific deletion of αE-catenin leads to heart failure and lethality in mice.

αE-catenin is a component of adherens junctions that link the cadherin-catenin complex to the actin cytoskeleton. The signaling function of this protein was recently revealed. In the present study, we investigated the role of αE-catenin in the pathogenesis of heart failure. We mated αE-catenin conditional knockout mice with αMHC-Cre mice and evaluated their mutant offspring. We found that αE-catenin knockout caused enlargement of the heart and atria, fibrosis, the upregulation of hypertrophic genes, and the dysregulation of fatty acid metabolism via the transcriptional activity of Yap and ß-catenin. The activation of canonical Wnt and Yap decreased the activity of main regulators of energy metabolism (i.e., adenosine monophosphate-activated protein kinase and peroxisome proliferator-activated receptor α) and dysregulated hypertrophic pathway activity (i.e., phosphatidylinositide 3-kinase/Akt, cyclic adenosine monophosphate/protein kinase A, and MEK1/extracellular signal regulated kinase 1/2). The loss of αE-catenin also negatively affected cardio-hemodynamic function via the protein kinase A pathway. Overall, we found that the embryonic heart-specific ablation of αE-catenin leads to the development of heart failure with age and premature death in mice. Thus, αE-catenin appears to have a crucial signaling function in the postnatal heart, and the dysfunction of this gene causes heart failure through canonical Wnt and Yap activation.

Response of Circulating Inflammatory Markers to Intermittent Hypoxia-Hyperoxia Training in Healthy Elderly People and Patients with Mild Cognitive Impairment.

Intermittent hypoxia-hyperoxia training (IHHT) is a non-pharmacological therapeutic modality for management of some chronic- and age-related pathologies, such as Alzheimer's disease (AD). Our previous studies demonstrated significant improvement of cognitive function after IHHT in the patients with mild cognitive impairment (MCI). The present study further investigated the effects of IHHT on pro-inflammatory factors in healthy elderly individuals and patients with early signs of AD. Twenty-nine subjects (13 healthy subjects without signs of cognitive impairment syndrome and 16 patients diagnosed with MCI; age 52 to 76 years) were divided into four groups: Healthy+Sham (n = 7), Healthy+IHHT (n = 6), MCI+Sham (n = 6), and MCI+IHHT (n = 10). IHHT was carried out 5 days per week for 3 weeks (total 15 sessions), and each daily session included 4 cycles of 5-min hypoxia (12% FIO2) and 3-min hyperoxia (33% FIO2). Decline in cognitive function indices was observed initially in both MCI+Sham and MCI+IHHT groups. The sham training did not alter any of the parameters, whereas IHHT resulted in improvement in latency of cognitive evoked potentials, along with elevation in APP110, GDF15 expression, and MMP9 activity in both healthy subjects and those with MCI. Increased MMP2 activity, HMGB1, and P-selectin expression and decreased NETs formation and Aß expression were also observed in the MCI+IHHT group. There was a negative correlation between MoCA score and the plasma GDF15 expression (R = −0.5799, p < 0.05) before the initiation of IHHT. The enhanced expression of GDF15 was also associated with longer latency of the event-related potentials P330 and N200 (R = 0.6263, p < 0.05 and R = 0.5715, p < 0.05, respectively). In conclusion, IHHT upregulated circulating levels of some inflammatory markers, which may represent potential triggers for cellular adaptive reprogramming, leading to therapeutic effects against cognitive dysfunction and neuropathological changes during progression of AD. Further investigation is needed to clarify if there is a causative relationship between the improved cognitive function and the elevated inflammatory markers following IHHT.