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

Nutriome is a set of alimentary factors for maintaining the body’s adaptive potential. Of particular importance for adaptation processes is the Nrf2/Keap1/ARE signaling system, the key regulatory factor of which is the transcription factor Nrf2. The enzymes that are markers of Nrf2 activation include NAD(P)H-quinone oxidoreductase and microsomal heme oxygenase-1. The aim of the study was to study the effect of minor dietary BAS of polyphenolic nature and indole-3-carbinol on the activity and expression of genes and proteins of Nrf2-regulated enzymes in the liver of rats when they were administered separately and in combination on the body of healthy intact animals. The effects of separate and combined intake of BAS into the body were studied in intact animals, including the following compounds separately and in combination in the diet of male Wistar rats for 14 days: rutin and hesperidin at a dose of 400 mg/kg body weight (b.w.); quercetin and resveratrol at 100 mg/kg b.w.; curcumin and quercetin at 200 mg/kg b.w.; indole-3-carbinol and epigallocatechin gallate at a dose of 50 mg/kg b.w. and 200 mg/kg b.w., respectively. The obtained data indicate that indole-3-carbinol and polyphenols of various classes have a significant effect on the activity and expression of proteins and genes of antioxidant defense enzymes: heme oxygenase-1 and NAD(P)H-quinone oxidoreductase, through the Nrf2/Keap1/ARE signaling mechanism, and at the posttranscriptional level, stimulating the adaptive potential of the body. The combined action of BAS in food can significantly modulate their individual effects.

The results of experimental and clinical studies indicate the involvement of platelets in the process of progression of malignant tumors of different localizations. Studying the effect of corticosteroids on thrombopoiesis in patients with adrenal cortex tumors will allow us to expand our understanding of the pathogenesis of adrenocortical cancer. Twenty two patients with adrenal cortex neoplasms were examined: 11 individuals with adrenocortical cancer (ACC) and 11 ones with adrenocortical adenoma (ACA). The diagnosis was confirmed based on the results of histological examination using the scale of L.M. Weiss. The age of patients was 58 (49–63) years, 5 (23%) of men were included in the study. No differences in the age, gender, or body mass index value between examined individuals with ACC and ACA were detected. In the preoperative period, all patients underwent clinical blood test with determination of leukocyte formula, calculation of systemic immune inflammation index (SII), urine steroid profiles were studied using gas chromatography/mass spectrometry. A larger number of platelets were obtained in ACC patients as compared with examined individuals with ACA: 282 (256‒310) × 10⁹ and 222 (194‒251) × 10⁹, р = 0.004. A lower SII value was detected in ACA patients as compared with ACC patients: 251 (186–354) and 618 (500–703), р = 0.002. Using gas chromatography/mass spectrometry method, higher urinary excretion of glucocorticoid metabolite tetrahydro-11-deoxycortisol, as well as androgens—dehydroepiandrosterone (DHEA) and etiocholanolone (Et) and 11β-OH-androsterone (androstenedione metabolites), progestogens—17-OH-pregnanolone, pregnanediol, pregnanetriol, pregnenediol, was demonstrated in ACC patients as compared with indices in ACA patients (p < 0.007). A linear dependence of the number of blood platelets on urinary excretion of Et (r = 0.81, p < 0.001) and DHEA (r = 0.94, p < 0.001), as well as SII on urinary excretion of DHEA (r = 0.90, p < 0.001), was demonstrated in all examined individuals.

The features of free radical oxidation in red blood cells coupled with the development of anemia in non-small cell lung cancer and breast cancer have been studied. In cancer, the imbalance of antioxidant enzymes activities was detected in red blood cells. For example, a 2-fold increase in the activity of superoxide dismutase (SOD) on the average (p < 0.001) was accompanied by a 1.5-fold decrease in the activity of glutathione peroxidase (GPO) (p < 0.005). According to the Spearman’s rank correlation, the decrease in GPO activity is coupled with the development of anemia, correlates with the decrease in hemoglobin (Hb) and hematocrit (HTC). The values of Spearman’s rank correlation coefficient are ρ = 0.76 for GPO and Hb; ρ = 0.74 for GPO and HTC. Anemia develops under the conditions of intensification of pro-oxidant processes and impaired gas transport function of red blood cells, as is demonstrated by positive correlation between the levels of malonic dialdehyde and 2,3-diphosphoglycerate (ρ = 0.54), which increased during its development (ρ = 0.74). The revealed impairments are universal and have been observed both in non-small cell lung cancer and in breast cancer.

This study describes the effects of the hepatitis C virus on lipid profile and some other parameters in patients with CRF. A clinical comparison was made between CRF patients with and without the hepatitis C virus. Abnormal lipid profiles in most patients with CRF are represented by high levels of serum cholesterol, triglyceride, LDL, and VLDL, and low levels of serum HDL cholesterol. While there was a lowering in serum cholesterol, triglyceride, LDL, and VLDL levels in CRF patients with hepatitis C infection, there is a positive association between the progression of CRF and fasting serum TG and cholesterol, regardless of age or gender, and the DM state of patients. HCV viral infection appeared to be related to decreased blood cholesterol and triglyceride levels, demonstrating that the HCV virus might possess a significant influence on the lipid profile within the serum of patients with chronic HCV infection. HCV binding to plasma lipoproteins has previously been demonstrated, as has the relationship between HCV infection and hypobetalipoproteinemia. The LDL receptor was additionally proposed to be one of the HCV receptors involved in HCV endocytosis, with LDL in the blood of patients effectively modulating HCV attachment to its target. HCV and LDL receptors could serve as competing inhibitors of LDL binding in HCV-infected individuals, creatinine and urea levels were elevated in HCV patients, reflecting renal abnormalities. HCV enables direct infection of renal tubular cells that contain ACE2 receptors on their surfaces.

The development of novel highly informative approaches to the assessment of chronic alcohol use is still an urgent problem, especially against the background of increase in alcohol dependence detected in 2023 in Russia for the first time over the past two decades. The present study was aimed at evaluating the level of the brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neuropeptide Y (NPY), and pituitary adenylate cyclase-activating peptide (PACAP) in the blood of tested subjects with different levels of alcohol use. For this purpose, the following groups of subjects were formed: healthy persons (group 1, n = 10), persons with periodical alcohol use (group 2, n = 10), persons with the consequences of using alcohol (group 3, n = 10), persons with the alcohol dependence syndrome in the acute phase (group 4, n = 10), and persons undergoing rehabilitation (group 5, n = 10). The studies have shown a relationship between ethanol consumption levels and the serum concentration of BDNF, which was 20%, 2.5 times and 40% lower relative to the control in patients from group 3, group 4 and group 5, respectively. The NPY concentration was 2.3-fold and 4.3-fold higher in the blood serum of patients from groups 2 and 3, respectively. The GDNF and PACAP levels in the blood of subjects from groups 2–5 were not significantly different from the control. The changes in the BDNF level are probably associated with the formation of new neuroadaptations and the unbalance of neuromediators typical of the dependence syndrome. The changes in the level of NPY are most likely a responce to an acute stress, more typical of subjects with the initial forms of alcoholic disorder. Thus, with BDNF and NPY used as markers, it is possible to objectify the strategy of differential diagnostics of mental and behavioral disordes associated with alcohol use. Evaluation of changes in these markers allows differentaition of persons periodically using alcohol without the development of complications and persons with harmful use of alcohol.

In recent years, regenerative medicine technologies, especially tissue engineering, have been increasingly used in dental implant surgeries. This review examines the main bioengineering trends that contribute to the success and longevity of dental implants. Since traditional implantation methods often face problems associated with insufficient integration of the implant into the alveolar bone tissue, innovative approaches such as the use of modified biomaterials, stem cells and growth factors open new horizons for improving clinical outcomes. Particular attention is paid to the development of multifunctional biomaterials that promote bone-tissue regeneration and improve osseointegration. Methods aimed at creating three-dimensional structures that imitate natural tissues are also considered. The review emphasizes an interdisciplinary approach that integrates knowledge from biology, engineering, and dentistry, which, in turn, facilitates the creation of individualized treatment strategies. In conclusion, this review highlights the importance of further research in tissue engineering to achieve higher standards in dental implantation and patient quality of life.

It is known that obesity changes the permeability of the intestinal wall, including for bacterial DNA. Therefore, obese patients differ from healthy individuals both in the content of bacterial DNA in the blood and in microbiotic metabolites. Indole metabolites are specific products of tryptophan conversion by intestinal microbiota. Some indoles are involved in the regulation of tight junction protein expression and are, thus, important for the regulation of intestinal permeability. The aim of our study was to investigate the relationship between the content of tryptophan metabolites in feces and the level of bacterial DNA in the blood. Materials and methods. The study included healthy donors without obesity (n = 138) and patients with obesity (n = 128) who were divided into subgroups with MHO (metabolically healthy obesity) and MUHO (metabolically unhealthy obesity). Bacterial DNA was isolated from venous blood samples, and metagenomic sequencing of the v3–v4 variable region of the 16S rRNA gene was performed. Both the frequency of isolation of individual taxa from samples and the share of these taxa in the total pool of bacterial DNA in the blood were compared. Concentrations of tryptophan metabolites in fecal extracts were determined by high-performance liquid chromatography with mass spectrometry. Chromatographic separation was performed using a Discovery PFP HS analytical column; a mass spectrometric detector based on an Agilent 6470 MRM triple quadrupole and electrospray ionization was used for detection. Results. Similar decreases in the content of metabolites of the kynurenine and indole pathways of tryptophan catabolism are noted in the intestines of patients with MHO and MUHO. In obesity, there is an increase in DNA translocation of the genera Rhodococcus, Streptomyces, CF231, Leuconostoc, Burkholderia, Providencia, and Enhydrobacter. Higher blood DNA content of Flavobacterium, Phascolarctobacterium, Kaistobacter, Comamonas, and Enhydrobacter was a feature of patients with MHO. In MUHO, translocation of Prevotella, Blautia, Coprococcus, Ruminococcus, Paracoccus, and Pseudomonas DNA into the blood was increased. In patients with MHO, a positive effect of intestinal kynurenine on the diversity of bacterial DNA in the blood was observed, whereas the concentration of 5-hydroxyindole-3-acetate in feces in MUHO was negatively associated with the diversity characteristics. Conclusions. The content of tryptophan metabolites in feces correlates with the presence of DNA of various taxa in the blood both negatively and positively, which indicates their role in regulating bacterial DNA translocation from the intestine.

Geodoram densiflorum or pink nodding orchid grows in wet habitats in Bangladesh. Rural people traditionally use this orchid’s pseudobulbs to treat skin inflammation, tumors and carbuncles. Though a protein from these bulbs previously showed antitumor activity against Ehrlich ascites carcinoma (EAC) cells in vitro, this study focused on proving this effect in vivo in a mice model and against a human cancer cell line. GDL exhibited around 45% growth inhibition against A549 cells at a concentration of 64 µg/mL implicating a caspase-dependent pathway modulated by caspase-3, -8, and -9 inhibitors. The condensed nuclei and morphological changes of GDL-treated cells indicating apoptosis also became evident by Hoechst 33342 and FITC-annexin V/PI staining. GDL up-regulated CASP9 and p53 while down-regulating PARP, MAPK, and STAT3 gene expression, suggesting the involvement of death receptor and intrinsic mitochondrial pathways. Flow cytometry analysis revealed GDL-induced G₀/G₁ phase cell cycle arrest. In vivo, GDL inhibited EAC cell proliferation by 48%, extending EAC-bearing mice lifespan by 37.05%, and improved hematological parameters, notably increasing red blood cell counts and hemoglobin levels to 2.41 × 10⁹ RBC/mL and 10.27 g/dL, respectively. These findings underscore the therapeutic potential of GDL, setting the stage for further in-depth research.

Background: Polycystic ovary syndrome (PCOS) is a prevalent hormonal disorder affecting reproductive-age women, often linked to metabolic issues like insulin resistance. Objective: this study aimed to evaluate ornithine decarboxylase (ODC) and ferric reducing capacity (FRC) levels in women with PCOS, with assess the effects of metformin and Primolut N treatment on their levels. Subjects and Methods: A case−control study was conducted with 150 married Iraqi women, categorized into three groups: 50 healthy controls, 50 untreated PCOS, 50 treated PCOS. Blood samples were analyzed for ODC, FRC levels and hormonal profiles. Statistical analysis applied independent t-test, Pearson’s correlation, ROC curve. Results: The ODC level was significantly increased while the FRC level was substantially decreased in PCOS patients compared to controls. Under metformin and Primolut N treatment, both ODC and FRC concentrations were improved to be close to their levels in control group. This reveals the potential role of ODC and FRC in PCOS progression. ROC results showed perfect sensitivity and specificity of ODC and FRC in PCOS diagnosing. Conclusions: The study introduces ODC and FRC as a valuable biomarker for diagnosing PCOS, highlighting its role in the disorder’s pathophysiology.

In this study, a change in the concentration of 8-hydroxy-2-deoxyguanosine (8-OHdG) in the oral fluid and plasma of model animals (rats) during subchronic intoxication with different classes of pesticides (thiram and imidacloprid) was studied. The intake of pesticides into the organism of rats with standard feed or water at a dose of 1/50 LD₅₀ for 28 days is accompanied by the production of an excess amount of reactive oxygen species (ROS) in the oral fluid and plasma. A cessation in pesticide intake leads to an insignificant decrease in ROS but does not reach the level of intact animals. An increase in the amount of 8-OHdG during subchronic intoxication with pesticides indicates the oxidative damage to DNA. In the oral fluid, the effect of thiram is accompanied by an increase in the amount of 8-OHdG on the day 21 of intoxication and in plasma at the day 7; at the same time, the level of 8-OHdG after the cessation of intoxication decreases to the control in the oral fluid and remains excessive in plasma. Imidacloprid leads to a growth in 8-OHdG in the oral fluid and plasma during 28 days of intoxication. After the cessation of the intake after 28 days, an increased content of 8-OHdG in the oral fluid and plasma remains. Imidacloprid causes a more pronounced oxidative effect on DNA as compared with thiram, which is accompanied by higher concentrations of 8‑OHdG in biological fluids. The accumulation of 8-OHdG indicates a depletion of antioxidant and reparative systems of the organism.