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

Linoleic acid (LA) is a fatty acid that cannot be synthesized by the body and is primarily found in plant seeds. It acts as a pro-inflammatory factor and its high consumption is associated with chronic inflammatory diseases. To better understand the effects of LA in the body, this study investigated its binding to human serum albumin (HSA) using spectroscopic and computational methods. Fluorescence measurements indicated a blue shift and increased emission intensity upon LA binding, consistent with reduced solvent exposure of Trp214. Far-UV CD showed alterations in HSA secondary structure. Esterase-activity assays suggested competitive inhibition by LA. Docking and Molecular dynamics results support van der Waals and weak hydrogen-bond-like interactions and reveal local flexibility changes consistent with the experimental data. This comprehensive analysis provides new insights into the LA-HSA interaction and the associated conformational changes in HSA, which correlate with its functional activity in the body.

A study was conducted on the regulatory effect of N-eicosapentaenoylethanolamine (EPEA) on the modification of the fatty acid (FA) composition of leukocytes in patients with asthma, in comparison with the effect of eicosapentaenoic acid ethyl ester (EPEE). The FA composition of leukocytes was analyzed by gas chromatography-mass spectrometry, both with and without the addition of experimental compounds. It was found that under the influence of EPEA, the FA composition of leukocytes undergoes more substantial changes: compared to the effect of EPEE, the total level of saturated FAs was 10% lower, monounsaturated FAs were 8% higher, and polyunsaturated FAs were 14% higher. Furthermore, in the samples with the addition of EPEA, an increase in eicosapentaenoic acid level was noted alongside a decrease in arachidonic acid level, which was not observed in the EPEE-treated samples. The evaluation of desaturation and elongation indices, based on product/substrate ratios, revealed a pronounced stimulatory effect of EPEA on the activity of enzymes of FA metabolism. The established changes indicate the potential of exogenous EPEA as a regulator of the FA balance of immune blood cells, which could be used to develop a strategy for the treatment of chronic inflammatory diseases.

α-N-Acetylgalactosaminidase (α-NaGalase) is produced by all cancer tumors and accumulates in the plasma of patients, which leads to the suppression of macrophage activity in patients with advanced cancer. Avarol (sesquiterpene hydroquinone) from Dysidea sp. and Damiron A (alkaloid) from Zyzzya fuliginosa were shown for the first time to be nonessential K-type activators of α-NaGalase isolated from the biomass of human colorectal cancer cells HT-29 and DLD-1, respectively. Bioinformatic analysis of the structures of healthy lysosomal α-NaGalase and similar enzymes, the genes of which were found in the genomes of human colorectal cancer cell lines of various lines with known point mutations, showed that amino acid substitutions are located in the loop structure on the outer surface of the enzyme. The active center region does not contain mutations. According to molecular docking results, the activators bind near the catalytic site of the enzyme and affect the microenvironment of the catalytic residue Asp 217, probably increasing its reactivity.

The paper presents a review of the application of nanotechnology in medicine (nanomedicine) in Russia and abroad. Particular attention is paid to the development and implementation of antibacterial nanocoatings for medical implants and instruments, as well as the role of nanomaterials in accelerating the healing of chronic wounds. Antibacterial nanomaterials can become a new stage in modern medicine in the treatment of bacterial infections due to their high efficiency, high strength and wear resistance. The paper provides a comparative analysis of such methods for the synthesis of antibacterial nanocoatings as the sol-gel method, chemical and physical vapor deposition (CVD, PVD), and atomic layer deposition (ALD). ALD technology allows creating antibacterial biocompatible nanofilms on various surfaces with high adhesion and strength, which increases the reliability and performance characteristics of such nanocoatings. Such nanofilms can be applied to implants to impart antibacterial and biocompatible properties to them in order to prevent postoperative complications. Dressings with antibacterial nanocoatings promote accelerated and safe healing of wounds, including chronic ones. The proposed technology can be used to manufacture dressings of a new type for accelerated wound healing.

Lichens are producers of a number of unique secondary metabolites. The most numerous and structurally diverse group of compounds characteristic of lichens are depsidones. To date, approximately 237 compounds belonging to the depsidones group have been described in lichens. At the same time, one or another biological activity has been described only for less than 10% of the total number of known compounds of this type. Depsidones exhibit antioxidant, cytotoxic, antimicrobial, anti-inflammatory, and other types of biological activity. At the same time, the mechanisms of biological activity of most depsidones are still not completely clear. This review summarizes data on the cytotoxic and antitumor effects as well as the molecular-cellular mechanisms of action of depsidones of the orcinol and β-orcinol types, emphasizing the need for further study of this group of compounds.

Plant extracts can be great substitutes to the infections instigated by multidrug-resistant (MDR) microbes due to the presence of naturally occurring phytochemical compounds enclosed within them. In this study the antimicrobial potential of eight different medicinal plants was tested against Escherichia coli (BTCB02), Staphylococcus aureus (BTCB03), and Bacillus subtilis (BTCB12) using disc diffusion method. Additionally, the cytotoxic activity via MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay against MDA-MD-231(MD Anderson) breast cancer cell lines was also conducted to examine their toxicity. Three crude extracts—aqueous, methanol, and ethanol—were prepared through maceration extraction. Amongst all the medicinal plants, Anogeissus latifolia disclosed the highest antimicrobial activity against E. coli, i.e., 28 ± 0.58 mm, whereas Viola odorata displayed 17 ± 0.78 mm, while aqueous Nardostachys jatamansi ethanol extracts revealed 14 ± 0.87 mm. Furthermore, B. subtilis revealed the highest antimicrobial activity with Aristolochia rotunda (methanol) (32 ± 1.23 mm), and Anogeissus latifolia exposed 22 ± 0.57 mm (ethanol) together with Rheum webbianum (ethanol) at 21 ± 0.23 mm. Moreover, S. aureus showed highest antimicrobial activity with Aristolochia rotunda aqueous extract (35 ± 1.02 mm) followed by Pistacia chinensis (32 ± 1.02 mm) and Anogeissus latifolia methanol extracts (23 ± 0.57 mm). After conducting series of experiments, plant samples Viola odorata (aqueous extract) and Acacia nilotica (ethanol extract) possessed highest cytotoxic activity against MDA-MD-231 cell line from 1 to 6% respectively. The results also verified the significance of phytochemicals in plants that are known to play a vital role during antimicrobial and cytotoxic activities.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths globally. In HCC, metabolic reprogramming leads to increased methionine synthesis, from homocysteine, which promotes tumor cell growth. Hyperhomocysteinemia often cause folate depletion. The present preliminary study was conducted to evaluate the diagnostic significance of MTR gene, homocysteine and 5-MTHF levels in HCC patients. A total of 40 participants were recruited in this study. HCC patients had higher homocysteine and reduced 5-MTHF levels as determined by enzyme cycling assay. mRNA expression of MTR gene was 5.6-fold higher in HCC patients relative to the control. A positive but moderate correlation (r = 0.61) was found between MTR gene and homocysteine levels while negative correlation (r = –0.67) was noted between MTR gene and 5-MTHF levels. Docking studies identified ALA442.A, GLY465.A and CYS463.A as potential amino acid residues of MTR protein interacting with homocysteine. Similarly, GLY38.A and ASP68.A of MTR protein were found to be potentially involved in hydrogen bond formation with 5-MTHF. The association of MTR gene with age and sex was not statistically significant. The study also reported that in HCC patients, homocysteine level, MTR gene expression, and prothrombin time were all upregulated while 5‑MTHF and albumin levels were reduced. Overall, the study provided complex interplay between the metabolites of one carbon metabolism (OCM) and their diagnostic and therapeutic potential. The results suggested that serum homocysteine, 5-MTHF levels, and MTR gene expression may serve as potential diagnostic biomarkers and may predict patient outcome in HCC.

The levels of potassium and sodium ions and their ratio (Na⁺/K⁺) were assessed in the blood serum of 54 healthy donors, as well as 31 patients with Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphomas (NHL) using the capillary zone electrophoresis. Comparison of the obtained results on the content of analytes with the literature data has shown that the observed values for potassium and sodium ions in healthy donors and patients are within the normal range. However, the K⁺ content was statistically significantly higher in patients (4.4 ± 0.6 mМ) compared to the group of healthy donors (3.9 ± 0.5 mM; p = 0.0001), which may indicate a tendency towards impaired Na⁺/K⁺-exchanging ATPase, electrolyte balance, and metabolic processes in patients with lymphoproliferative diseases (LPD). As a result, the ratio of these cations was statistically significantly lower in patients (32 ± 5; p = 0.0013) compared to the control group (36 ± 4). The analysis of the homogeneity of variance between the group of healthy donors and patients showed that the variances were not homogeneous for the sodium cation (p = 0.0153). The average concentrations of Na⁺ and K⁺ ions did not differ significantly between the age groups of 18–50 and 51–85 years in healthy people and patients. The analysis of the homogeneity of variance between the age groups also revealed no statistically significant differences (p > 0.05), with the exception of sodium cation in the age group of 18–50 years, where the variances were nonhomogeneous (p = 0.046). There were no statistically significant differences in the content of potassium, sodium ions and their ratio depending on the type of lymphoproliferative disease: HL and NHL, within the sample under study. This suggests that the content of these analytes does not depend on the type of LPD in this population.

We report a green synthesis of ZnO and ZnO@Ag nanostructures using an aqueous extract of Spinacia oleracea as a reducing and stabilizing agent. The products were characterized by UV–Vis, XRD, FTIR, Raman, and SEM. Pure ZnO exhibits a characteristic UV absorption around 370 nm and a wurtzite XRD pattern. Biosynthesized ZnO nanoparticles show antibacterial activity against Bacillus (inhibition zone = 30 mm), Klebsiella (25 mm), Staphylococcus aureus (16 mm) and Proteus vulgaris (14 mm) at 100 µg/disc. Doping with Ag produced ZnO@Ag nanostructures with significantly enhanced antibacterial activity, achieving a maximum inhibition zone up to 43 mm for S. aureus and 33 mm for P. vulgaris at a 100% Ag precursor weight ratio. The improved activity is attributed to the synergistic combined effects of increased ROS generation by ZnO and Ag⁺-mediated membrane damage; structural and optical evidence of the Ag–ZnO interaction is shown by the observed red-shift in UV-vis absorption and changes in Raman/FTIR features. This green route is simple, low-cost and yields highly effective antibacterial nanomaterials suitable for further biomedical or environmental testing.

hnRNPA2/B1 is an RNA-binding protein involved in the regulation of transcription, mRNA stability, and also functions as one of the regulators of the intracellular antiviral response. Its role in intranuclear recognition of foreign DNA from herpes simplex virus type 1 as well as in the initiation and amplification of antiviral signaling cascades has been demonstrated. In this study, we have shown for the first time the relocalization of hnRNPA2B1 mRNA from the nucleus to the cytoplasm in cells supporting hepatitis B virus (HBV) replication. We have also demonstrated, for the first time, the anti-HBV activity of hnRNPA2B1 and its ability to destabilize the major HBV transcript. Notably, in HBV model systems, hnRNPA2B1 did not alter the expression or localization of mRNAs encoding antiviral factors. The suppression of HBV replication was not accompanied by changes in interferon-β production. Taken together, hnRNPA2B1 exerts an antiviral activity in HBV models, and its mechanism of action is not associated with the activation of intracellular antiviral cascades or pathways analogous to intranuclear recognition of the herpes simplex virus DNA.