Latest Articles

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.

Bacteria of the species Streptococcus pneumoniae, dominant in the etiological structure of community-acquired pneumonia in children, are represent a serious problem in the field of human infectious pathology. Detailed molecular and genetic characteristics of eleven S. pneumoniae strains isolated from sputum samples of children with community-acquired pneumonia were obtained using whole genome sequencing and bioinformatic analysis. Based on the analysis of the nucleotide sequences of seven housekeeping genes (aroE, gdh, gki, recP, spi, xpt, ddl), it was found that S. pneumoniae strains included in the study belong to six sequence types: ST1367, ST819, ST1262, ST180, ST15069, ST66. Using SeroBA algorithm S. pneumoniae strains were assigned to five serotypes:11C, 22F, 15C, 9N, 3. Genome annotation using ResFinder and CARD databases allowed us to identify determinants of resistance to macrolides (ermB, RImA), fluoroquinolones (patA, patB, pmrA), lincosamides (RImA), aminoglycosides (aph(3')-Ia) and tetracyclines (tetM and tet32). A high frequency of detection of pathogenicity genes encoding choline-binding proteins, fibronectin-binding proteins, pneumolysin, autolysin, hyaluronidase, neuraminidase, capsule proteins, zinc metalloproteinase in the genome of S. pneumoniae strains was noted.  Phylogenetic analysis of the nucleotide sequences of the genome of Nishny Novgorod strains and strains deposited in GenBank/NCBI showed a high level of genetic variability of pneumococci circulating both in Russia and abroad.

Vitex negundo is a medicinal plant renowned for its wide spectrum of therapeutic properties, including significant anticancer activity. This study explores the inhibitory effects of V. negundo methanolic extract and essential oil on α-amylase purified from the serum of Iraqi lung cancer patients, as well as their cytotoxic effects on the A549 human lung cancer cell line. α-Amylase, an enzyme involved in carbohydrate metabolism, exhibits altered activity under cancerous conditions, making it a potential therapeutic target. The enzyme was purified through a multi-step procedure comprising ammonium sulfate precipitation, dialysis, ion-exchange chromatography, and gel filtration chromatography. This process resulted in an increase in specific activity from 0.94 to 17.0 U/mg protein. Both extracts of V. negundo were assessed for their capacity to inhibit α-amylase activity and reduce the viability of lung cancer cells. The methanolic extract demonstrated a more pronounced inhibitory effect on α-amylase (88.4% at 10 µg/mL) compared to the essential oil (77.0% at 10 µg/mL). Moreover, MTT assay results indicated concentration -dependent cytotoxicity against A549 cells, with IC₅₀ values of 68.79 µg/mL for the methanolic extract and 81.14 µg/mL for the essential oil. These findings underscore the potential of V. negundo—particularly its methanolic extract—as a promising natural anticancer agent, capable of targeting cancer-related metabolic pathways and suppressing tumor cell viability. The results warrant further investigation into the development of V. negundo-based therapeutics for lung cancer treatment.