Acta biochimica Polonica最新文献

RNA splicing is a fundamental post-transcriptional mechanism that enables the generation of diverse mRNA isoforms from a single gene, thereby expanding proteomic complexity and regulating cell fate decisions. Emerging evidence highlights that dysregulated splicing contributes to the onset and progression of various bone-related diseases, including osteoporosis, osteoarthritis, and skeletal malignancies. In this review, we summarize current knowledge on the core mechanisms of pre-mRNA splicing, with emphasis on alternative splicing events that modulate bone cell differentiation, matrix formation, and tissue homeostasis. We further discuss how aberrant splicing impacts signaling pathways involved in bone metabolism and disease pathogenesis, and we explore the epigenetic and RNA-binding protein networks that fine-tune these processes. Finally, we examine the therapeutic potential of targeting splicing machinery or correcting mis-splicing events using small molecules, antisense oligonucleotides, and RNA-based approaches. This comprehensive overview provides mechanistic insights and highlights splicing regulation as a promising avenue for the diagnosis and treatment of skeletal disorders.

Background: Vitamin D deficiency is a major public health concern, worldwide yet data on the adult population in Türkiye remain limited. This study aimed to determine the prevalence of vitamin D deficiency and its associated risk factors in Tokat Province, Türkiye.

Methods: A population based cross-sectional study was conducted among 2,225 adults aged ≥20 years through multistage stratified cluster sampling from both urban and rural areas. Data were obtained via structured questionnaires, anthropometric measurements, and fasting blood samples. Serum 25-hydroxyvitamin D3 [25(OH)D3] levels were measured and categorized as deficient (<10 ng/mL), insufficient (10-20 ng/mL), or sufficient (>20 ng/mL). Multivariate logistic regression was used to identify predictors of deficiency.

Results: The mean age was 47.2 ± 15.2 years, and 54.8% were women. Vitamin D deficiency was present in 38.7% and insufficiency in 46.4% of participants. Deficiency was significantly more common among women, the older adult, obese individuals, and those with lower education levels and chronic diseases (p < 0.05). In the adjusted model female sex (aOR 0.19, 95% CI 0.14-0.27), obesity (aOR 1.76, 95% CI 1.36-2.28), and lower education were independent predictors of deficiency.

Conclusion: Vitamin D deficiency and insufficiency are highly prevalent among adults in Tokat Province, despite adequate sunlight exposure in the region. Public health strategies/interventions should focus on high-risk groups, prioritize particularly women, older adults, and obese individuals through screening, education, and targeted supplementation.

In most vertebrates, hemoglobin's primary function is to transport oxygen and carbon dioxide. Hemoglobin is also expressed in cells such as dopaminergic neurons and chondrocytes, as well as in organelles such as mitochondria. Depending on its location, hemoglobin subunits can interact with proteins involved in various functions, including anion exchange, nitric oxide synthesis, and ATP synthesis. These interactions suggest that hemoglobin has diverse regulatory roles beyond gas transport. During hypoxia and an excess of nitrite and protons, deoxygenated hemoglobin exhibits nitrite reductase activity and produces nitric oxide, a gaseous signaling molecule. Hemoglobin-derived nitric oxide is associated with vasodilation in mammals and the inhibition of mitochondrial respiration in cell cultures. This raises the question of whether hemoglobin functions as a gasoreceptor in these cells or organelles. The HIF1α/PHD2 pathway in mammals and cysteine oxidases in plants are largely responsible for sensing hypoxia, but the identity of oxygen gasoreceptors analogous to the mammalian nitric oxide gasoreceptor soluble guanylate cyclase and the plant ethylene gasoreceptor kinases remains unknown. Since the heme-based dual oxygen-binding and catalytic domain emerged earlier than the allosteric regions, I propose hemoglobin as an oxygen proto-gasoreceptor derivative. Furthermore, since hemoglobin interacts with and regulates proteins depending on its oxygen binding state, I propose that hemoglobin functions as an oxygen gasoreceptor in split-component signal transduction systems. Recognizing hemoglobin as a gasoreceptor will expand the emerging field of gasocrinology to encompass gases that were previously considered primarily metabolic substrates.

Zinc, an essential trace element, plays a pivotal role in numerous physiological processes, including antioxidant defense, immune regulation, and metabolic homeostasis. However, excessive Zn supplementation disrupts these pathways, contributing to the pathogenesis of chronic conditions such as obesity, diabetes mellitus, hypertension, and cardiovascular diseases. This systematic review explores the dual-edged nature of Zn by examining its molecular impacts, including antioxidant enzyme dysregulation, leptin receptor resistance, and inflammatory marker modulation. While optimal Zn levels confer protective benefits, such as improved insulin sensitivity and reduced oxidative stress, excessive intake triggers systemic inflammation, oxidative damage, and metabolic dysregulation. Contrasting evidence highlights dose-dependent effects and variability based on genetic and environmental factors, underscoring the need for tailored dietary guidelines. Knowledge gaps persist regarding Zn toxicity thresholds, long-term impacts, and interactions with other nutrients. Public health policies must prioritize balanced supplementation strategies to mitigate risks while leveraging Zn's therapeutic potential in chronic disease prevention. This review emphasizes the importance of precision nutrition and evidence-based approaches to optimize Zn's benefits while minimizing its adverse effects.

Biology textbooks lack precise terms to describe oxygen-based inter-organismal signaling between oxygen-producing and aerobic organisms. To address this gap, I recently proposed the concept of gasocrine signaling, which encompasses all signaling mediated by gaseous molecules and gasoreceptors within and between cells, organisms, and even abiotic factors. Given the fundamental importance of gaseous molecules for life, I propose the gasocrine hypothesis: all cells require gasocrine signaling. This hypothesis can be divided into three sub-hypotheses: First, all living organisms composed of one or more cells require gasocrine signaling to sense, communicate, grow, and propagate. Second, gasocrine signaling mediated via gasoreceptor proteins (or yet to be identified gas-sensing riboceptors) is the most essential cellular and inter-organismal signaling. Third, acellular entities arising from or replicating in pre-existing cells require gasocrine signaling. I propose several potential experiments to falsify these hypotheses. If they withstand falsification, the gasocrine hypothesis would supplement cell theory. It would also provide a novel framework for understanding fundamental biological principles, cellular and organismal communication, and the role of abiotic factors. Furthermore, it establishes the foundation for the emerging field of gasocrinology, which is critical in the context of a changing environment.

Fatty acids play important, yet different roles in bacterial physiology, specifically their growth, either stimulating or inhibiting this parameter which are of biotechnological importance. Here, we present results showing to what degree short- and medium-chain fatty acids (butyric acid (butanoic acid, C4:0); caproic acid (hexanoic acid, C6:0); caprylic acid (octanoic acid, C8:0)), used at relatively low concentrations (in a range of μg/mL, contrary to previously reported mg/mL which revealed inhibitory effects on bacterial growth) affect growth of Escherichia coli K-12 (MG1655 laboratory strain) depending on various conditions. In rich medium (LB) positive effects of all tested fatty acids on E. coli growth were observed, while temperature of incubation (growth at 25 °C and 37 °C was assessed) modulated these effects. In contrast, a slight but significant growth inhibition by fatty acids was observed in a minimal medium (M9) supplemented with glucose. Nonetheless, in minimal medium containing acetate, the effects of these compounds varied, being either positive or negative depending on their concentrations. No measurable bacterial growth was observed in the case of the presence of any tested fatty acids when primary carbon source (glucose or acetate) was removed from a minimal medium before addition of butyric acid, caproic acid or caprylic acid. Our results indicated that effects of low concentrations of fatty acids on E. coli cells depend on growth conditions of bacterial cultures. This may be of biotechnological importance, especially for modulating E. coli growth by using different compositions of media and incubation temperatures.

The aim of our work was to analyze new functionalized analogues of 5-substituted-2(1H)-pyridone containing of natural amino acids derivatives as a potential drugs in idiopathic pulmonary fibrosis (IPF). The creation of connections with natural amino acids was aimed at obtaining anti-fibrotic compounds with better water solubility, increased hydrophilicity, lower toxicity and better pharmacokinetic properties. For the docking studies the corresponding grid box parameters were used: PARPγ, ALK5 andp38. During our initial research we have synthesized and performed biological in vitro studies for two analogues selected on the basis of molecular modeling: 6b and 6f. MTT test have been performed to select concentrations of PFD derivatives for subsequent analysis. We have analyzed HLA-DR and CXCR4 expression on fibroblasts and 24 h migration of TGF-β1-stimulated fibroblasts. We have also explored proliferation and production of TGF-β1 as well as IL-17 by CD3/CD28 beads-stimulated PBMCs. Preliminary studies show that the designed compounds exhibit promising potential as anti-fibrotic therapeutics. Therefore, their activity is worth further exploring.

Studies have identified specific salivary biomarkers associated with different types of cancer, including oral, lung, and pancreatic cancers. These biomarkers can be proteins, DNA fragments, or other molecules that indicate the presence or progression of the disease. Saliva-based cancer detection offers the potential for earlier diagnosis, leading to better treatment outcomes. Additionally, salivary biomarkers can help tailor treatment plans to individual patients, improving their chances of successful recovery.

Research aimed to examine the effects of β-blockers on cytokine release in Jurkat cells under basal conditions and during oxidative stress. Oxidative stress was induced in Jurkat cells through the application of hydrogen peroxide (H₂O₂). Subsequently, β-blockers were administered to the incubation medium for 24 h, encompassing both intact and oxidatively stressed cell conditions. For β-blocker toxicity screening, the viability of Jurkat cells was determined using the MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) test. The IL-6, IL-17, and TNF-α content were measured in the supernatant of Jurkat cells incubated under different conditions. The study results show that propranolol, metoprolol, carvedilol, but not nebivolol, revealed toxic effects on the intact Jurkat cells (p_c-p = 0.0001; p_c-m > 0.0001; p_c-c = 0.0003; p_c-n = 0.0525). Under oxidative stress conditions, the viability of Jurkat cells decreased significantly (p_c-H2O2 = 0.0001). Propranolol and metoprolol did not affect ((p_c-p = 0.0001; p_c-m > 0.0001), while nebivolol and carvedilol improved the viability of Jurkat cells incubated under oxidative stress conditions (p_c-n = 0.002; p_c-c = 0.0002). Oxidative stress significantly increased the cytokines (IL-6, TNF-α, IL-17) expression levels (p_c-H2O2 < 0.0001; p_c-H2O2 < 0.0001; p_c-H2O2 < 0.0001) in Jurkat cells. Propranolol, carvedilol, nebivolol, and metoprolol did not significantly affect the expression levels of IL-6, TNF-α, and IL-17 in intact Jurkat cells, but decreased IL-6, TNF-α, and did not change IL-17 expression levels in Jurkat cells incubated under oxidative stress conditions. This study demonstrates that β-blockers can influence redox-sensitive cytokine pathways in Jurkat T lymphocytes when they are under oxidative stress. All the agents tested inhibited the production of IL-6 and TNF-α, but nebivolol and carvedilol showed the strongest protective and anti-inflammatory effects. These effects likely result from their combined properties, including antioxidant effects, nitric oxide modulation, and the regulation of NF-κB/MAPK pathways. In contrast, propranolol and metoprolol exhibited more limited activity. These findings suggest that third-generation β-blockers may offer both cardiovascular and immunomodulatory benefits, although further validation in primary immune cells and in vivo models is still required.