Current Issues in Molecular Biology最新文献

Indeterminate serological results for SARS-CoV-2 antibodies create diagnostic uncertainty, requiring repeat testing after 14-21 days to establish seroconversion. This study evaluated whether direct viral detection methods could provide immediate diagnostic information in serum samples with indeterminate antibody results. We analyzed 163 serum samples from clinically healthy individuals collected during March-December 2020 in Bulgaria. Samples were categorized by screening ELISA (IgA/M/G) as positive (n = 69), negative (n = 47), or indeterminate (n = 47). All samples underwent quantitative IgG ELISA, rapid antibody tests, rapid antigen detection (viral nucleoprotein), and RT-nested PCR. Among samples with indeterminate antibody results, 27.7% (13/47; 95% CI: 15.6-42.6%) tested positive by rapid antigen detection and 12.8% (6/47; 95% CI: 4.8-25.7%) by RT-PCR. All PCR-positive samples were also antigen-positive (Cohen's κ = 0.69). Viral detection rates showed a gradient: antibody-positive samples 30.4% (antigen) and 16.4% (PCR), indeterminate samples 27.7% and 12.8%, antibody-negative samples 10.6% and 4.3%, respectively. The algorithm we proposed and the diagnostic methods used enable the application of certain approaches to differentiate infected from uninfected clinically healthy people, in case of intermediate antibody results. Direct viral detection identified evidence of potential SARS-CoV-2 infection in more than one-quarter of sera with indeterminate antibody results. These findings suggest immediate viral detection testing may complement standard serological approaches, though clinical validation through longitudinal studies is essential before routine implementation.

Background: Sepsis is a leading cause of mortality in intensive care units, with liver dysfunction representing a critical determinant of poor outcome, mainly associated with excessive inflammation and oxidative stress. Lycopene, a carotenoid with potent antioxidant and anti-inflammatory properties, has been proposed as a potential therapeutic agent. This study investigated whether lycopene supplementation mitigates lipopolysaccharide-induced oxidative and inflammatory liver injury in rats.

Methods: Male Wistar rats, divided into four groups, were exposed to either lipopolysaccharide or a combination of lipopolysaccharide (10 mg/kg) and lycopene (6 mg/kg). In order to assess liver damage induced by lipopolysaccharide, hepatocellular injury markers, oxidative stress indices, nitric oxide metabolism, glutathione redox status, apoptotic enzyme activity, and inflammatory mediators were assessed in serum and liver tissue.

Results: Lipopolysaccharide induced marked hepatocellular damage, characterized by elevated serum liver-cell damage parameters, and liver tissue xanthine oxidase, myeloperoxidase, thiobrabituric reactive substances, protein carbonyl content, deoxyribonuclease I/II activity, nuclear factor kappa B, tumor necrosis factor-α, and interleukin-6, alongside depletion of reduced glutathione and reduced glutathione reductase and glutathione peroxidase activities. Lyc pretreatment significantly attenuated liver enzyme leakage, oxidative damage, and cytokine release while restoring reduced glutathione and glutathione reductase activity. In contrast, lycopene had limited effects on glutathione peroxidase activity, nitric oxide/inducible nitric oxide synthase signaling, and nuclear factor erythroid 2-related factor 2 expression.

Conclusions: These findings demonstrate that lycopene confers partial hepatoprotection in endotoxemic rats, primarily through suppression of oxidative damage and nuclear factor kappa B-mediated inflammation. Further studies are needed to clarify tissue-specific mechanisms and optimize dosing strategies in order to increase the efficacy of this carotenoid.

Essential oil-derived compounds such as eugenol, thymol, cinnamaldehyde, and carvacrol exhibit potent antimicrobial and anti-inflammatory properties, making them promising candidates for therapeutic and industrial applications. This review examines the current evidence regarding the mechanisms of action, efficacy, and ability to disrupt quorum sensing and biofilm formation of essential oil-derived compounds against a broad spectrum of Gram-positive and Gram-negative bacteria, including multidrug-resistant (MDR) strains. The anti-inflammatory activity of these compounds is also highlighted, with emphasis on their modulation of key signaling pathways such as nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs), and their ability to downregulate pro-inflammatory cytokines. However, challenges persist, including cytotoxicity at high concentrations, chemical instability, poor water solubility, and variable pharmacokinetics. Advanced delivery systems such as nano encapsulation and synergistic formulations offer potential strategies to overcome these limitations. This review highlights both the therapeutic potential and the current limitations of these natural compounds, emphasizing the need for continued research to translate preclinical findings into clinical applications.

This study focused on investigating the effects of dietary counseling on antioxidant intakes and how diet can influence reactive oxygen species (ROS) levels and consequently oxidative stress (OS) during pregnancy. At the end of the first trimester of pregnancy (12-13 week of pregnancy), 80 women were randomized into a control group and to an intervention group to receive individual dietary counseling. In the intervention group (n = 60), the dietary counseling about the Mediterranean diet (MD) was carried out during six online meetings every 15 days and focused on antioxidant nutrients and their intake. They were encouraged to follow the antioxidant-rich diet for 12 weeks, including increased consumption of antioxidant-rich foods such as ≥5 servings/day of vegetables, ≥2 servings/day of fruit, ≥8.5 servings/day of wholegrains and 3-4 servings/week of lean meat. In the control group (n = 20) dietary counseling included generic, standard of care guidance about nutrition in pregnancy and was only discussed during a single session. OS biomarkers, particularly (ROS) and Total Antioxidant Capacity (TAC) levels, were analyzed before and after the study duration in women's serum. The results of the study showed lower ROS and higher TAC levels after intervention compared to the levels before intervention, as well as compared to the levels of the control group. In conclusion, dietary counseling improved the intake of antioxidant nutrients from food during pregnancy, as depicted by oxidative stress biomarkers' levels, and may influence the observed impacts of these dietary patterns on pregnancy outcomes.

Introduction: Prostate cancer (PC) accounts for around 10% of all cancers worldwide and is the fourth most common neoplasm. Localized PC has high cure rates when diagnosed early, but 35% of patients progress to the metastatic form. The search for new molecular markers, such as microRNAs, is fundamental to improving diagnosis and treatment. The role of miR-10a is controversial between tumor tissues, opening a niche for studies on their role in PC. Objectives: To evaluate the role of miR-10a in metastatic PC cell lines, focusing on the mechanisms of proliferation, migration, and invasion, and to analyze the expression in surgical specimens of localized PC. Methods: Three commercial metastatic PC cell lines were used: LNCaP, DU145 and PC-3. Expression of mimic miR-10a was induced by cell transfection, followed by extraction of miRNA and total RNA. The synthesis of complementary DNA (cDNA) and analysis by real-time PCR enabled the expression of miR-10a and the VEGF, MYC, and HAS3 genes to be assessed. Matrigel, colony formation, invasion, and migration assays were evaluated for the transfected cells. The surgical specimens were used to evaluate the miR-10a expression. Results: Transfected cells with mimic significantly increased the expression of miR-10a in the LNCaP (p = 0.0179), PC-3 (p ≤ 0.001), and DU145 (p ≤ 0.001) cell lines. Transfected cells reduced cell invasion in the PC-3 (p = 0.001) and DU-145 (p = 0.0004) cell lines and decreased cell migration and proliferation. In surgical specimens, miR-10a expression was higher in PC compared to Benign Prostatic Hyperplasia (p = 0.0010). Conclusions: Increased expression of miR-10a affects cell migration, invasion, and proliferation, showing potential as a therapeutic target in treating PC.

Cerebral ischemic reperfusion injury (CIRI) induces irreversible neurological dysfunction with high morbidity and mortality, yet effective clinical interventions remain limited. This study focused on ferroptosis in CIRI and explored the neuroprotective components and mechanisms of Pomelo peel essential oil (PPEO)-a product derived from Guangxi's characteristic Shatian pomelo. Sprague-Dawley rats were used to establish two CIRI models: focal CIRI via Middle Cerebral Artery Occlusion (MCAO) and global CIRI via Cardiac Arrest/Cardiopulmonary Resuscitation (CA/CPR). Analyses were conducted using metabolomics, transcriptomics, histopathological staining, biochemical assays, RT-qPCR, Western blotting (WB), and molecular docking. Metabolomic results showed altered lipid-related metabolites in both models, predominantly unsaturated fatty acids and components of the arachidonic acid (AA) metabolic pathway. Transcriptomic analysis revealed significant upregulation of PTGS1/2 in the MCAO model. Nootkatone and β-pinene improved neuronal morphology, increased glutathione peroxidase 4 (GPX4) levels, and enhanced neurological scores. Notably, Nootkatone exhibited strong binding affinity to ALOX15, and reduced lipid metabolic disturbances in the CA/CPR model. AA metabolism varies with CIRI severity: it is inflammation-driven in focal CIRI and ferroptosis-associated in global CIRI. As a key component of PPEO, Nootkatone antagonizes ferroptosis via the ACSL4-LPCAT3-ALOX15 axis, offering a novel therapeutic target for global CIRI after CA/CPR.

Type 2 Diabetes Mellitus (T2DM) is a chronic disease caused by the resistance of tissues to the actions of insulin as well as the progressive failure to produce adequate amounts of insulin in pancreatic β-cells. Research has further shown that T2DM is characterized by a generalized state of low-grade inflammation; this inflammation is often related to overnutrition and obesity leading to an excess storage of lipid particles in adipose cells. Eventually, this will stimulate the pathophysiological pathways of cellular stress and inflammation. The inflammation characterizing T2DM can then contribute, along with other mechanisms of hyperglycemia, to the emergence of cardiovascular disease. Due to the resulting heart disease, many patients with T2DM may be inevitably required to undergo cardiac surgery with cardiopulmonary bypass (CPB), a process also characterized by an intense inflammatory response with possible effects and disruptions in immune system functions. It is thus the purpose of this narrative review to summarize and present evidence in the literature related to the inflammatory interplay occurring between T2DM, cardiovascular disease, and cardiac surgery with CPB.

Premature ovarian failure (POF) is characterized by oxidative stress, cellular senescence, and impaired steroidogenesis, yet current therapies remain limited in effectiveness. Thymol, a natural monoterpene, exhibits antioxidant and anti-inflammatory properties. Network pharmacology and molecular docking identified multiple potential targets, notably the Janus kinase 1 (JAK1)-signal transducer and activator of transcription 3 (STAT3) pathway. In tert-butyl hydroperoxide (t-BHP)-induced human granulosa-like tumor cells (n = 3), 40 μg/mL thymol increased cell viability by approximately 45%, restored superoxide dismutase, catalase, and glutathione peroxidase activities to nearly twice those of the model group, and reduced reactive oxygen species accumulation by about 35% (p < 0.05). It also decreased senescence markers p53, p21, and p16 by 40-60% and inhibited JAK1-STAT3 phosphorylation (n = 3, p < 0.05). In aged pregnant mice (n = 4 per group), thymol increased viable fetus numbers by about 40%, elevated serum estradiol and progesterone levels to 1.6-1.8-fold of aged controls, and downregulated ovarian aging markers (p < 0.05). Collectively, these findings indicate that thymol mitigates oxidative stress-induced ovarian aging by modulating JAK1-STAT3 signaling and restoring steroidogenic function, supporting its potential as a natural candidate for delaying ovarian senescence.

Contact dermatitis is a common inflammatory skin disorder triggered by exposure to allergens or irritants and characterized by erythema, swelling, and immune cell infiltration. In this study, we investigated the anti-inflammatory effects of exosome-like nanovesicles derived from Peucedanum japonicum Thunb. (PjELNs) using a 2,4,6-trinitrochlorobenzene (TNCB)-induced mouse model of contact dermatitis. Intraperitoneal administration of PjELNs markedly reduced ear swelling and histopathological damage and decreased infiltration of inflammatory immune cells, particularly neutrophils. Moreover, PjELNs downregulated the expression of key pro-inflammatory cytokines, including CXCL2 and IL-1β, in the affected tissue. These findings indicate that PjELNs alleviate contact dermatitis-associated inflammation and suggest their potential as a novel plant-derived therapeutic modality for inflammatory skin diseases.

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) with radiation therapy can enhance the sensitivity of cancer cells by inhibiting DNA repair pathways. To determine the most suitable PARP inhibitor for radiosensitization in cancer cells, we compared various types of clinically used PARPis in lung cancer A549 cells. We found that most PARP inhibitors showed radiosensitization effects on A549 cells. ER10 values for talazoparib, olaparib rucaparib, ABT888 and niraparib were 1.5, 1.8, 2.8, 1.4, and 1.4, respectively. Talazoparib showed a radiosensitization effect at its lowest concentration. Talazoparib is a potent PARP inhibitor and has been used in clinical settings for several types of cancer as an anti-cancer agent. We thus focused on how talazoparib causes radiosensitization in lung cancer A549 cells. As a result of the combination of talazoparib and γ-irradiation, we observed an increased level of cellular senescence accompanied by a decrease in mitochondrial membrane potential. When the p21 gene was knocked down, both the decrease in mitochondrial membrane potential and senescence level were attenuated, suggesting that p21 is involved in senescence induction after γ-irradiation combined with talazoparib treatment. Taken together, we showed that PARP inhibitor talazoparib treatment in combination with γ-irradiation causes cellular senescence in lung cancer cells, involving p21 function.