Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry最新文献

Many disorders can be accurately diagnosed using ribonucleic acids (RNAs). A panel of RNAs specific to colorectal cancer (CRC), generated in silico, was used in this study. This panel is composed of Nucleosome Assembly LINC00654 (Long Intergenic Non-Protein Coding RNA 654) long nucleolar RNA, SRY-box transcription factor 5 (sox5 mRNA) mRNA, small nucleolar RNA host gene (Sox5), and homo sapiens microRNA-133a (miR-133a) from the genetic and epigenetic database based on in silico data analysis. Validation and characterization of the proposed RNA network were done by qPCR in sera samples from 130 cases. These cases included 70 CRC patients with a malignant tumour, 40 patients with a benign tumour, and 20 healthy controls. Moreover, the panel expression was verified in a representative CRC, HT29, cell line. Our data revealed that the expression of LINC00654 and Sox5 RNAs was higher in the sera from CRC compared with the control group, while miR-133a showed the opposite expression pattern. These data may, at least in part, validate the in-silico relationship and enhance the possibility that miR-133a might be sponged by LINC00654 and thus leave the chance for Sox5 upregulation in CRC patients. Taken together, our findings may introduce a novel molecular network. Therefore, this RNA panel could be recommended as a potential diagnostic marker for CRC patients.

The processes of progressive decrease in muscle mass and weakening of mitochondrial function that occur during aging in skeletal muscles remain poorly understood as does, above all, the cause-and-effect relationship between the ultrastructure of mitochondria and atrophic processes in skeletal muscles. An ultrastructural study of the features of the internal structural organization of mitochondria during aging of skeletal muscle was carried out on representatives of rapidly aging mammalian species (Wistar rats, OXYS, mice) and representatives of long-lived species: the naked mole rat (Heterocephalus glaber) and human. Previously unknown, age-related structural changes in the internal organization of skeletal muscle mitochondria in OXYS rats at the age of 24 months are shown: the appearance in each mitochondria of local areas of altered arrangement of cristae in the form of stellate structures, as well as the presence of extremely large structural formations, apparently the result of destructive processes in mitochondria, as well as the appearance of mitochondria that are abnormal in size and internal ultrastructure. It was shown that structural changes in mice at the age of 10 months and naked mole rats at the age of 11 years were multidirectional. If disturbances in the normal ultrastructure in mice affected not only mitochondria but also muscle fibers and the sarcoplasmic reticulum, then not only no pathological changes are observed in mole rats but also, on the contrary, the powerfully developed structure of mitochondria indicates the functional activity of these organelles. For the first time, the ultrastructure of mitochondria in human skeletal muscle at the age of 68–81 and 25–28 years was compared using biopsy material. In elderly patients, the phenomenon of mitochondrial proliferation is shown: a compensatory structural response to mitochondrial dysfunction. Mitochondria are small, with a small number of cristae. In young people, the ultrastructure of mitochondria corresponded to classical ideas about the features of the structural organization of skeletal muscle mitochondria. Literary ideas about the possible role of autophagy in the development of aging processes are considered.

Mast cells (MCs) are an important population of connective tissue cells that play a key role in the development of allergic diseases. The main pathway of MC activation in allergies is associated with the interaction of antigen complexes with immunoglobulin E and their subsequent binding to the FcεRI receptor. This leads to rapid release of secretory granules and cytokine production. In recent years, there has been increasing evidence for the involvement of autophagy in many processes, including MC function. Therefore, autophagy regulators can be used as potential inhibitors of MC activity and as therapeutic agents for the treatment of allergic diseases. In the present study, we investigated the effects of two autophagy inhibitors SBI-0206965 and LY294002, and one autophagy activator rapamycin on FcεRI-dependent activation of RBL-2H3, which usually used as model of MCs and basophils. Cell activation was assessed by determining the content of the secretory granule marker β-hexosaminidase and the levels of the cytokines TNF, IL-4 and IL-13. Treatment of cells with SBI-0206965 and LY294002 was shown to reduce FcεRI-dependent degranulation and IL-4 cytokine secretion by RBL-2H3 cells, while the use of rapamycin resulted in reduction of the level of IL-13 cytokine. This indicates the prospect of potential application of these autophagy regulators in the therapy of allergic diseases.

Background: This study assessed the association of vitamin D status with the frequency of incidence of metabolic health risk factors, including obesity, hypo-alpha cholesterol, hypertriglyceridemia, carbohydrate metabolism disorders (hyperglycemia and insulin resistance), and cardiovascular system stress conditions in men of different ages. Aim: The research aimed at identifying cardiometabolic disorders in young, mature, and elderly men with suboptimal and optimal concentrations of 25(OH) vitamin D. Materials and methods: Two hundred and thirty-four Magadan oblast residents at early adulthood, maturity, and extreme old age participated in the survey. Each age group was divided into two samples: with optimal or suboptimal vitamin D level. We used photometric, immunochemiluminescent research methods, as well as standard methods for assessing body mass index and cardiovascular system. Results: The results showed rather high incidence of suboptimal 25(OH) vitamin D levels among the Magadan oblast population. Optimal vitamin D concentration was associated with a significant fall in the percentage of people with a hypertensive character of cardiovascular performance, with a lower incidence of hypoalphacholesterolemia, hyperglycemia, hypertriglyceridemia, and insulin resistance throughout all age groups, and was more common in elderly men. Conclusions: The suboptimal concentration of vitamin D can be considered as an additional nonstandard driving factor for age-associated cardiometabolic disorders. Metabolic healthcare needs preventive measures to level these disorders to contribute to active longevity and life expectancy.

Different efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) has been observed between lung cancer patients with 19 exon deletion (19Del) and with L858R mutation. We investigate the multi-omics information from the TCGA Lung adenocarcinoma (LUAD) dataset and validate it using the GEO (GSE190139, GSE147377) and MSK datasets. Somatic loss-of-function alteration of RBM10 and altered Immune infiltration profile correlated with L858R decreased survival. Meanwhile, 9p21.3 loss, CDKN2B methylation, and increased cell cycle-related gene expression are differential characteristics in the L858R mutation group. Comprehensive genomic and phenotypic analysis of the EGFR-mutated lung cancer subtypes reveals distinctive features of each subtype, laying the groundwork for subtype-specific treatment and care options for lung cancer patients.

The E3 ubiquitin ligase Cullin 5 (CUL5) has been linked to a variety of cell biological functions, such as developmental process regulation, DNA repair, and cell cycle control, but the role of CUL5 in the unfolded protein response (UPR) remains unclear. We found that the knocked-down of the CUL5 gene results in the upregulated levels of binding immunoglobulin protein (BiP) protein, a major chaperone protein in unfolded protein response (UPR), whereas the over-expression of CUL5 downregulated BiP protein levels in breast cancer cells. Further investigation revealed that CUL5 binds with BiP, leading to the ubiquitination of BiP. Our findings suggest that CUL5 is involved critically in the proteasome-degradation of BiP, leading to weaker UPR.

This work is an overview of deep machine learning methods aimed at predicting binding sites in protein structures. Several classes of methods are selected: prediction of binding sites for small molecules, proteins, and nucleic acids. For each class, various approaches to prediction are considered (prediction of binding atoms, residues, surfaces, pockets). Specifics of feature selection and neural network architectures inherent to each class and approach are highlighted, and an attempt is made to explain these specifics and foresee the further direction of their development.

By comparing the reaction catalyzed by phosphoenolpyruvate carboxylase with the one by the ligase or synthetase, it was suggested here that phosphoenolpyruvate carboxylase (EC 4.1.1.31, PEPC) should be classified as the synthetase. And accordingly it was thought here that the existing classification standard of synthetases put forward by the International Enzyme Committee should be supplemented. That is, synthetases should also include the enzyme which catalyzes the non phosphoric acid portion of a high-energy phosphoric acid compound (except (d)NTP) to synthesize one new substance with the other substance, meanwhile the high-energy phosphoric acid compound above is hydrolyzed in the reaction accompanying with the release of energy stored in its high-energy phosphate bond. It was suggested here that the formula of the reaction catalyzed by the enzyme should be X~Pi + Y + H₂O → H₃PO₄ + X-Y.

The most predominant fatty acid in olive oil, oleic acid (OA), lowers LDL (low-density lipoprotein) cholesterol and may raise HDL (high-density lipoprotein cholesterol). As a result, it effectively improves heart function and prevents heart diseases. In the current research, the OA interaction with HSA (human serum albumin) was evaluated by spectroscopic and computational modeling methods to determine the impact of OA on the body. Observations from the absorption spectra proved the complexation of HSA with OA. An enhancement in the fluorescence intensity shows that interactions between HSA and OA have altered the milieu enclosing the fluorophore and altered the structures of HSA. Van der Waals forces and hydrogen bonds were determined to be the main factors producing the HSA-OA complex by molecular docking. The HSA structure’s α-helix was decreased, as per evidence of far-UV CD spectroscopy. The activity of HSA represented OA binding with HSA in a competitive mode. Investigation of the esterase activity of HSA reveals that OA could inhibit its activity. The information obtained from the MD (Molecular dynamics) simulation proved that the binding of the OA causes stability in the HSA structure, and the structure of the HSA becomes more compact by OA binding and reduces the flexibility of the residues. The data obtained in the present work improves our understanding of the activity and mechanism of binding and provides a valuable experimental approach for investigating the OA-HSA compound.

Post-translational modifications (PTMs) are crucial for all biological processes and offer insights into protein functions, including their activity state, subcellular location, solubility, folding, trafficking, and protein−protein interactions. Amino acids modified by PTMs act as molecular switches, influencing protein function and characteristics, and increasing proteome complexity. Krüppel-like transcription factors (KLFs) are a family of transcription factors that regulate essential cellular processes such as proliferation, differentiation, migration, programmed cell death, and various cancer-relevant pathways. In this study we investigated the effect of phosphorylation on the binding affinity and stability of KLF6-SV1 (Krüppel-like factor 6 splice variant 1) interactions with its binding partners, potentially revealing a mechanism for its oncogenic activity. KLF6-SV1 and binding partners interactions were computationally analyzed to evaluate the role of phosphorylation in KLF6-SV1 on their binding affinity and stability. In the present study, it was found that despite a decrease in the binding force between KLF6-SV1 and TWIST1, KLF6-SV1 and MMP9, KLF6-SV1 and SNAI1 upon phosphorylation, the overall energy of each complex decreased, resulting in increased stability. This suggests that phosphorylation plays a significant role in activating KLF6-SV1 and its partner’s oncogenic activities by making the complex stable. This study provides valuable insights into the underlying molecular mechanism of cancer pathogenesis and suggests that KLF6-SV1 phosphorylation is one of the critical events in cancer pathogenesis.