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.
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.
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
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
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
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.
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.
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.
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.
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
Capillary zone electrophoresis (CZE) was employed to quantify major cations (K+, Na+, Ca2+, Mg2+) and anions (Cl−, SO_4^2 - , PO_4^3 - , lactate, citrate) in blood serum samples obtained from 40 healthy donors aged from 20 to 85 years. Ammonium concentration (µmol/L) was additionally measured in capillary blood, as this cation was not reliably detectable in deproteinized serum using CZE due to its methodological limitations. Statistical analysis revealed sex-based differences only for ammonium (p = 0.001), with higher levels observed in men compared to women (median 97.5 µmol/L vs. 89 µmol/L, respectively). Statistically significant age-related differences were observed for phosphate (p = 0.04), ionized calcium (p = 0.008), as well as Na/K (p = 0.01) and Mg/Ca (p = 0.003) ratios. Ionized calcium levels in older donors (65–85 years) were lower than in younger groups and fell below reference ranges. Lactate concentrations in young and middle-aged donors slightly exceeded literature reference values. This study established reference intervals in blood serum for all the analytes studied, including sulfate and citrate ions, for which there is almost no information in the literature about the normal concentrations of these ions. Correlation analysis revealed statistically significant positive correlations between chloride and lactate, potassium and sodium, chloride and sulfate, and magnesium and ionized calcium in serum (p < 0.05). These results support the applicability of CZE for ion determination in blood serum and provide valuable reference data for clinical practice.
This study is the first to investigate the biochemical interrelationships of circulating lipoprotein(a) (Lp(a)) with markers of dyslipidemia (apoB, non-HDL-C), systemic inflammation (hs-CRP), and the lipid metabolism regulator PCSK9 in a sample of conditionally healthy residents of the Republic of Karelia (n = 213, aged 40–59). Lp(a) levels were measured using immunoturbidimetry. An elevated Lp(a) level (>30 mg/dL) was found in 17.35
Fatty acid ethanolamides exhibit a variety of biological effects. Recently, it has been shown that diethanolamides of palmitic and stearic acids are capable of suppressing the growth of tumor cells. At the same time, these substances are characterized by low solubility in aqueous environments, which necessitates the search for ways to increase their solubility and biological activity. One approach to solving this problem could be the use of analogues of natural metabolites of fatty acid ethanolamides as solubilizers: diethanolammonium salts of fatty acids, which are ionogenic surfactants. The aim of this work is to study the effect of diethanolammonium salts of fatty acids on the solubilization and antitumor effects of palmitoyl and stearoyl diethanolamides. In experiments in vitro, palmitoyl and stearoyl diethanolamides have been shown to inhibit cell growth of C6 and HeLa glioma tumor lines. Diethanolammonium salts of caprylic, capric, lauric, palmitic, and stearic acids have a weak effect on cell growth; however, at the same time, they enhance the inhibitory effect of palmitoyldiethanolamide by 1.1–10.9 times and stearoyldiethanolamide by 1.1–8.3 times. The severity of the inhibitory effects of palmitoyl and stearoyl diethanolamides and their compositions with diethanolammonium salts of fatty acids depends on the dose of the drugs and the cell type. In relation to normal rat brain cells, the effects of the drugs are manifested to a lesser extent compared to the effects on rat C6 glioma tumor cells. In general, the ability of diethanolammonium salts of fatty acids to promote solubilization and enhance the antitumor efficacy of diethanolamides of palmitic and stearic acids has been demonstrated in vitro.
An analysis of saliva lipid extracts using Fourier transform infrared spectroscopy was performed in breast cancer, fibroadenomas, and healthy controls. A general decrease in the absorption band intensities of salivary lipids was demonstrated, along with changes in their structure in terms of the ratio of unbranched to branched lipid molecules. Significant factors influencing changes in the salivary lipid profile were found to be HER2 receptor expression and the breast cancer phenotype. The greatest differences from other subtypes were demonstrated for non-luminal breast cancer. Overall, changes in lipid metabolism in breast cancer, especially in the most aggressive subtypes, require further study, as they involve numerous potential therapeutic targets that could improve disease treatment, and therefore overall patient survival and quality of life.
Tissue spheroids, which are three-dimensional cellular aggregates, represent a powerful tool in biomedical research and tissue engineering. This review summarizes contemporary methods of spheroid biofabrication, including the hanging drop technique, use of nonadhesive surfaces, microfluidic systems, bioreactors, magnetic and acoustic levitation, chemical inducers of aggregation, and hydrogel matrices. Their advantages, limitations, and applications are discussed in detail. Special attention is paid to the process of spheroid fusion as a key step in the creation of larger tissue constructs as well as to methods for the quantitative assessment of its kinetics. The core of the review is an analysis of the molecular mechanisms underlying spheroid formation and fusion. The key roles of cell adhesion molecules—such as E-cadherin, N-cadherin, and integrins—cytoskeletal elements (actin microfilaments and microtubules), signaling pathways (Wnt/β-catenin), and extracellular matrix components (collagen, fibronectin, laminin) are described. Current understanding of cell self-organization processes and the prospects for using spheroids to create functional tissue models and constructs in regenerative medicine and oncology research are discussed.
The nonessential amino acids serine and glycine play an important role in the human organism. They are necessary for the synthesis of proteins and peptides, nucleic acids and lipids, and for maintaining the antioxidant status of the cells. The organism’s need for these amino acids is met by their intake with food or by de novo synthesis intracellularly using glycolysis metabolites. Oncological transformation of cells causes increased proliferation and growth of tumor cells. To survive under stress, cancer cells need additional amounts of Ser and Gly, which leads to activation of their de novo synthesis. Metabolic reprogramming of cancer cells is recognized as a hallmark of tumor cells and plays a critical role in cell proliferation and survival. Amino acids are essential for cancer cells not only as nutrients but also as signaling molecules that can regulate gene expression and promote epigenetic modification. A key metabolic pathway influencing the epigenetic state of cancer cells is one-carbon metabolism, which includes the folate and methionine cycles. The interrelation of these cycles generates S-adenosylmethionine (SAM), a universal methyl donor required for DNA and histone methylation. The one-carbon units required for nucleotide synthesis are generated in a reaction catalyzed by cytosolic (SHMT1) and mitochondrial (SHMT2) serine hydroxymethyltransferases. Although SHMT1 and SHMT2 catalyze the same biochemical reactions, they play different biological roles in tumors. In most tumors, SHMT1 gene expression is decreased, while SHMT2 gene expression is increased. In various tumors, one-carbon units are recycled in Ser/Gly biosynthesis, which is accompanied by higher expression of the gene for the key enzyme of mitochondrial Gly synthesis, SHMT2. This enzyme catalyzes the reaction of formation of Gly and tetrahydrofolate-related one-carbon unit from Ser, supporting purine and thymidine synthesis and promoting tumor growth. The pro-oncogenic role of SHMT2 has been established, which is necessary for the survival of cancer cells and tumor growth in vivo with a poor prognosis for the patient. To maintain a high level of SHMT2 activity, increased expression of the SHMT2 gene is necessary, which is facilitated by complex regulatory mechanisms in tumor cells. SHMT2 expression can be regulated by methylation, acetylation, succinylation, phosphorylation, and lactylation. In addition, SHMT2 activity can be regulated by transcription factors, post-translational modification, or microRNA. SHMT2 depletion induces apoptosis by activating autophagy through metabolic reprogramming of tumor cells. The search for drugs that can target these enzymes is relevant for oncology. Therefore, studying the mechanisms of regulation of the activity of these key enzymes in cancer cells is of great importance. The review considers some mechanisms of regulation of the activity of these enzyme markers in cancer cells and the role of microRNA in modulating their activity.
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder. Despite the high morbidity and mortality associated with COPD, underdiagnosis rates for the disease phenotypes remain as high as 70
Melanoma is one of the most dangerous malignant tumors. The number of melanoma cases is increasing especially in light skinned individuals. Fast metastasis development can play an important role in in the ineffectiveness of antitumor therapy and be a main reason of poor prognosis for patients with melanoma. Signals associated with extracellular matrix play an important role in metastasis formation. Dacarbazine is used for melanoma monotherapy, but the effectivity is less than 5
To date, chemotherapeutic agents remain the primary method for treating many oncological diseases, including breast cancer (BC). However, numerous side effects caused by the indiscriminate destruction of actively dividing cells limit the safe use of chemotherapeutic agents in clinical practice. Due to the combination of unique properties of nanoparticles, including high biocompatibility and the ability to overcome biological barriers, biological nanoparticles (BNP) are a promising tool for reducing the unwanted toxicity of modern chemotherapeutic agents. This study examined the efficacy of delivering ultra-low concentrations of doxorubicin (0.0544 mg/kg), a dose that is 100 times less than the single therapeutic dose used in a mouse model, using orthotopic and functionalized exosome-like nanoparticles in BC models in vitro and in vivo. It was shown that doxorubicin loaded in BNP exhibited increased cytotoxic activity compared to the free chemotherapeutic agent in vitro. Moreover, a more pronounced activity of functionalized (targeted) nanoparticles towards breast cancer cell receptors was demonstrated compared to orthotopic particles obtained from the tumor. In an in vivo experiment on mice with BC, doxorubicin in ultra-low doses incorporated in BNP did not show an anti-tumor effect; however, there was a trend towards a reduction in tumor nodule size with the administration of orthotopic and functionalized BNP with doxorubicin. Therefore, (1) BNP enhance anti-tumor activity, allowing for a reduced dose of the administered chemotherapeutic agent, (2) the creation of targeted nanoparticles ensures enhanced accumulation of the drug in tumor cells, but (3) ultra-low doses of the chemotherapeutic agent do not have a pronounced effect on BC growth in vivo. The results of the study indicate the potential for using BNP as a strategy to reduce off-target toxicity of modern chemotherapeutic agents.
This study examined the structures of SpCas9 endonuclease of Streptococcus pyogenes and their evolutionary variants using different computational biophysical models to investigate the behavior of hydration in these endonucleases. Although the mechanism of SpCas9 is well understood from an evolutionary perspective, its hydration has not been thoroughly explored. The study found that all endonucleases tended to compact together and expose less surface area to water as a solvent, resulting in a significant loss of water molecules from the hydration layer, as occurs in the folding of many globular proteins. A comparative analysis revealed that the distribution of water molecules in the hydration shell and PI domain, which is responsible for the biological recognition function of ligand, differed between each endonuclease. All endonucleases have a higher density in their hydration shell in relation to the density of water as a solvent, with SpCas9 having the highest density in the hydration shell (19 P_( n_w) and the degree of hydration P_( δ_h) in the evolutionary direction from the oldest to the current. These findings suggest that water molecules in the hydration shell play an important role in the conformational changes, biological recognition, and activity of this endonuclease of great biotechnological interest.
