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

Gut microbiota can influence the central nervous system through the transport of microbial metabolites by the microbiota−gut−brain axis. These metabolites like short chain fatty acids and amino acids, as well as enzymes encoded by microbiota species, can alter neurotransmitters production. This likely contributes to disorders like addiction, which are developed due to changes in brain neurochemistry caused by imbalances in neurotransmitter levels as a result of substance abuse. The long-term destabilization of these systems generates an allostatic state where substance consumption is needed to maintain the altered levels of neurotransmitters and avoid withdrawal symptoms. In addition, drug-induced dysbiosis decreases the diversity of beneficial bacteria and promotes the growth of harmful bacteria in the gut. Thus, impairing intestinal barrier function and serum metabolite levels. The influence dysbiosis has on metabolite production negatively impacts neurotransmitter pathways, worsening physical and psychological symptoms of withdrawal and likely contributing to the development of addiction.

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% in patients with metastatic melanoma. The aim of this work is to assess the alterations in expression levels of extracellular matrix (ECM) components and associated factors after dacarbazine treatment. The authors found that dacarbazine treatment increased the expression levels of such ECM components as collagen type IV, fibronectin, laminin, and vitronectin, whereas tenascin expression level was decreased. In addition, expression levels of HIPK1 and RBL1 were also increased, while expression level of integrin ITGB8 decreased. These alterations are supposed to be connected with epigenic regulation of gene expression by alkylating agent dacarbazine and associated with the promotion of cancer progression and metastasis.

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%. While previous studies have prioritized their focus on exacerbation COPD due to its acute clinical impact and substantial disease burden, research on the stable COPD phenotype remains limited, despite its high prevalence in outpatient settings. The present study employed a comprehensive proteomic/bioinformatics approach to identify unique proteins differentially expressed in the stable COPD phenotype and explored their functional significance. The biomarker potential of these proteins was further evaluated using in silico analysis. Our study identified three DEPs—leukemia inhibitory factor receptor (LIFR), properdin and olfactory receptor 10A7 (OR10A7) that consistently exhibited altered expression in stable COPD. ROC analysis indicated strong predictive potential, with AUC values of 0.86, 0.87, and 0.95 for LIFR, properdin and OR10A7 respectively. These findings provide valuable insights into the pathogenesis of stable COPD and identify potential diagnostic biomarkers and therapeutic targets for future investigation.

We enrolled 43 children aged 2–8 years with a diagnosis of autism spectrum disorder (ASD) and 43 age- and sex-matched healthy controls. The aim was to evaluate routinely available laboratory parameters as accessible markers that could aid ASD diagnosis and treatment monitoring, thereby contributing to the elucidation of ASD etiopathogenesis. Serum ALT, AST, iron (Fe), unsaturated iron-binding capacity (UIBC), ferritin, folate, vitamin B12, TSH, free T4, vitamin D, uric acid, insulin, glucose, total cholesterol, HDL, LDL, triglycerides, C-reactive protein (CRP), and creatinine, as well as complete blood count (CBC) indices, were statistically compared between groups. Samples were analyzed on automated hormone, clinical chemistry, and hematology analyzers. Logistic regression was used to assess the association between platelet count and ASD status. No statistically significant between-group differences were observed for ALT, glucose, CRP, insulin, total cholesterol, HDL, LDL, triglycerides, creatinine, iron, UIBC, ferritin, folate, vitamin B12, TSH, free T4, RBC, hemoglobin, hematocrit, or MCV (all p > 0.05). WBC, platelet, uric acid, AST, and vitamin D levels were significantly higher in the ASD group than in controls (all p < 0.05). In logistic regression, higher platelet count was associated with increased odds of ASD (OR = 1.019 per unit increase in the measurement scale used), controlling for covariates. ASD is diagnosed based on DSM-5 criteria and supplementary scales. This study identifies objective, readily measurable blood parameters that may support ASD diagnosis and guide subsequent treatment; larger, longitudinal studies are warranted to confirm these associations.

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%) and the lowest being the primitive endonuclease SCA (4%) in relation to the bulk water. The previously reported catalytic activity of these endonucleases toward the OCA2 and TYR genes increased nonlinearly with both maximum of probability density of the number of water molecules ({{P}_{{left( {{{n}_{w}}} right)}}}) and the degree of hydration (~{{P}_{{left( {{{delta }_{h}}} right)}}}) 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.

The use of resveratrol and L-carnitine (RC) in the complex as components of dietary products and food supplements is considered a potential approach to the dietary therapy of obesity and associated pathologies. However, the interactions between these bioactive substances upon ingestion, particularly their combined effects on global gene expression patterns, remain poorly understood. We investigated the hepatic transcriptome in male Wistar rats fed a control diet (CD) or a high-fat/high-carbohydrate diet (HFCD), supplemented with low (RCl) or high (RCh) dose RC for 64 days. HFCD altered the expression of 757 genes, while HFCD with RC induced more modest changes (179–243 genes). A key finding was a significant negative correlation between gene expression changes induced by HFCD and RC within the HFCD, indicating a compensatory effect of the supplement. Only two genes, Asns and RT1-CE10, responded to both RC doses in both diets. Bioinformatics analysis revealed that RC targeted four metabolic pathways (KEGGs) also disrupted by HFCD: drug and xenobiotic metabolism by cytochrome P450, retinol metabolism, and steroid hormone biosynthesis. The PPAR signaling pathway was altered by both RC doses in CD-fed rats and by RCh in HFCD-fed rats. These findings identify xenobiotic detoxification, retinoid/steroid metabolism, and fatty acid oxidation as key transcriptomic targets through which the RC supplement may counteract diet-induced obesity. The interaction between resveratrol and L-carnitine at the gene expression level should be considered when developing combined dietary supplements.

In recent decades, bioengineering and regenerative medicine have shown significant progress in restoring lost teeth and tissue. The review is devoted to modern possibilities of bioengineering intervention in tooth regeneration, including advances in the field of stem cells, 3D printing, biomaterials, gene therapy, and tissue engineering. Embryonic mechanisms of tooth formation and key signaling pathways, such as BMP (Bone Morphogenetic Proteins), FGF (Fibroblast Growth Factors), Wnt, and Shh (Sonic Hedgehog), are the basis for the development of new therapeutic strategies. One of the main directions is the use of different types of stem cells, including dental pulp cells (DPSCs), deciduous teeth (SHED), and periodontal cells (PDLSCs), as well as alternative sources, such as mesenchymal stem cells from bone marrow and adipose tissue. An important aspect is the use of innovative materials, such as biodegradable polymers, natural matrices, and nanostructured coatings, to create 3D scaffolds that support tissue growth. Particular attention is paid to molecular methods of intervention, including the use of growth factors (BMP-2, FGF-2, VEGF, TGF-β), gene therapy (e.g., using CRISPR/Cas9), and controlled gene expression, to activate odontogenesis. Prospects for creating teeth are being considered de novo and with dental organoids as are problems associated with the integration of regenerated tissues into the body, including issues of vascularization, innervation, and immunocompatibility. Important issues remain control over directed cell differentiation, the durability of regenerated teeth, and the ethical and legal aspects of using genetic engineering. Translation of these methods into clinical practice requires the integration of bioengineering, bioinformatics, materials science, and clinical dentistry as well as the development of clinical trials and appropriate legal regulation. In the coming decades, dental regeneration may become an important element of personalized medicine, which will require further improvement of technologies, testing of new biomaterials and more precise control of cellular processes, which will ultimately ensure the successful implementation of this approach in clinical practice.

Myogenic bioengineering has emerged as a promising field aimed at repairing or regenerating damaged muscle tissues triggered by trauma, diseases, or congenital defects. Poly(lactic acid) (PLA) nanofibrous scaffolding has appealed to progressive attraction as an innovative support for prospective therapy in renewal/or repair medicine. Herein, high aspect ratio PLA nanofibers were fabricated using electrospinning and characterized by means of various sophisticated techniques such as XRD, SEM, TGA and FTIR spectroscopy. There is no information regarding the interaction of muscle cells with PLA. Thus, muscle precursor cells were exposed to various doses of electrospun PLA nanoscaffolds to test proliferation and in vitro biocompatibility. Cell viability was assessed by CCK-8 at standard time periods. The structure of treated myoblasts was scanned by a phase contrast microscope and to check the growing profile Bio-SEM was used. Furthermore, antimicrobial activity was explored against Gram-positive Staphylococcus aureus. The findings specify that PLA nanoscaffolds exhibit mild antimicrobial efficiency. Besides, the myoblasts demonstrated proliferative behavior on nanoscaffolds. Our investigation highlights that PLA nanofibers hold significant promise for developing biomimetic cellular scaffolds. Moreover, the PLA nanoscaffolds developed in this study show great potential for tissue engineering, particularly in muscle regeneration. Its high biocompatibility and ability to support myoblast attachment, proliferation and differentiation make it a promising biomaterial implant for regenerative medicine.