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Noroviruses are the leading cause of outbreaks of nonbacterial gastroenteritis and the second most common cause of all viral intestinal infections. An effective norovirus vaccine is expected to help reduce the incidence of intestinal infections, but intensive efforts to develop such a vaccine have so far been unsuccessful. Failures in vaccine development may be due to the high heterogeneity of noroviruses and/or the hypothetical low protective efficacy of the immune response to the most common virus variants, such as GII.4 Sydney 2012. The subject of the study was potential vaccine components – virus-like particles (VLPs), formed from VP1 of norovirus GII.4 Sydney 2012 (VP1N) and VLPs from a fragment of this protein containing the shell domain and hinge region (SN). We investigated the effect of VLPs on the ability of human dendritic cells (DCs) to recruit T cells into the immune response in vitro. VLP-treated DCs were cultured with pure CD4⁺ T cells, and then T cell maturity and cytokine production were assessed. It has been shown that VP1N-treated DCs, but not SN-treated DCs, have an increased ability to shift the ratio of T cell from naïve T cells to more mature central memory T cells and stimulate IL-17 production. Intracellular cytokine assay revealed no differences in T-helper type 1 (Th1), Th17 and Th1/17 levels between mixed cultures with VP1N-treated DCs and control DCs. Apparently, the increase in IL-17 production occurs due to an increase in the activity of mature Th17, and not the maturation of new producer cells.

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Heart failure (HF), a major pathology of the myocardium, is characterized by impaired cardiac function that leads to an abnormal enlargement of the heart, known as hypertrophy. In the study of the molecular mechanisms of HF pathogenesis, animal models play a crucial role. To characterize induced HF in animal models, biochemical approaches, such as quantifying the concentration of biomarkers in blood serum, are extremely important. Here we report a new immunochemical test system based on the measurement of the concentration of the B-type natriuretic peptide, protein biomarker of HF and hypertrophy, that can be utilized for characterization of HF development in rats and serve as a tool for further BNP concentration analysis.

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder in which neuroinflammation plays a major role in its pathogenesis, alongside the formation of amyloid plaques and neurofibrillary tangles. Necroptosis, a recently discovered regulated form of cell death mediated by the kinases RIPK1 and RIPK3, is considered one of the mechanisms contributing to neuroinflammation and neuronal death in AD. In this study, we evaluated the effect of chronic necroptosis inhibition using Necrostatin-1, a RIPK1 blocker, on the progression of neurodegeneration in aged 5xFAD mice, a model of the familial form of AD. Over a 12-week treatment period, the animals’ neurological status was assessed, followed by evaluation of long-term memory using the Morris water maze test, histological analysis of the prefrontal cortex and hippocampus, and RT-PCR analysis of the expression of key genes associated with necroptosis and inflammation. Chronic administration of Nec-1 significantly slowed the progression of neurological deficits in both male and female 5xFAD mice. Inhibition of necroptosis prevented the loss of normal neurons, reduced the number of hyperchromic cells, and decreased the severity of pericellular and perivascular edema in the examined brain regions. However, in the Morris water maze test, learning and memory improved only partially in males, but not in female 5xFAD mice. This may be attributed to the increased expression of the anti-inflammatory cytokine IL-10 in the cortex and hippocampus of males. The results obtained indicate that inhibition of necroptosis by Necrostatin-1 represents a promising therapeutic approach for correcting neurological impairments and mitigating morphological brain alterations in Alzheimer’s disease.

Primary lactose non-persistence (LNP, hypolactasia) represents an autosomal-recessive condition, which is mainly attributed to the presence of the ancestral C-allele in the MCM6 -13910C>T (rs4988235) variant regulating the expression of the lactase (LCT) gene in individuals of European ancestry. Since the studies linking lactose intolerance C-allele and caloric accumulation, as well as gastrointestinal symptoms remain ambiguous to date, we decided to examine for a possible relation between the rs4988235 lactose intolerance allele and certain health parameters (body mass index, waist circumference, breastfeeding duration, and existing gastrointestinal tract diseases) in individuals (N = 2912) from four regions of the Volga-Ural region (VUR), i.e., Sverdlovsk Oblast, Republic of Bashkortostan, Chelaybinsk Oblast, and Udmurt Republic. In addition, we sought to clarify the genotype and allele frequencies of the MCM6 rs4988235 in the large sample from the VUR based on territorial and ethnic specificity. While examining a relation between several health conditions and the MCM6 variant, we determined a link between the rs4988235 CC genotype and prolonged breastfeeding duration (more than 1 year) in the total sample (OR = 1.63, 95%CI 2.32–5.88, p = 0.005) and in Russians (OR = 1.75, 95%CI 2.85–4.16, p = 0.024), which became more significant in individuals with a full-term period of gestation (more than 36 weeks) (OR = 1.67, 95%CI 1.13–2.45, p = 0.009) and was positively associated with higher birth weight (β = 3.11, p = 1.8x10^-3). Findings obtained point to a compensatory effect of prolonged breastfeeding on diminishing manifestation of genetically predisposed primary hypolactasia.