Search Results (217)

Background/Objectives: Obesity increases reactive oxygen species (ROS), thereby triggering oxidative stress. Coriander seeds contain polyphenolic compounds that act as natural antioxidants to reduce oxidative stress. Coriander seed ethanolic extract has been proven to decrease malondialdehyde and increase catalase activity in the liver of high-fat-diet-fed rats. Thus, coriander seeds are thought to protect against obesity-induced oxidative liver damage; however, their molecular mechanism has not been revealed. Nuclear factor erythroid 2-related factor 2 (Nrf2) and Forkhead Box O3 (FOXO3) are transcription factors involved in cellular antioxidant regulation (e.g., superoxide dismutase/SOD, glutathione peroxidase/GPx expression, and reduced glutathione/GSH) that are negatively regulated by Kelch-like ECH-associated Protein 1 (Keap1) and 14-3-3 protein to maintain cellular homeostasis. This study aimed to analyze the regulation of antioxidant expression through in silico and in vivo experiments. Methods: The in silico study assessed the potential of coriander seed ethanolic extract to inhibit Keap1 and 14-3-3 using molecular docking. Then, the drug-likeness, pharmacokinetics, and toxicity of the top three compounds were analyzed. Meanwhile, the in vivo study investigated how the coriander seed ethanolic extract impacted the level of Nrf2, FOXO3, and their downstream effectors (T-SOD, MnSOD, GPx, and GSH). The in vivo study involved five groups of rats with obesity induced by a high-fat diet that were fed with 100 mg/kgBW coriander seed ethanolic extract for 12 weeks. Results: The in silico tests revealed that shionoside b had the highest potential to inhibit Keap1 (ΔG = −8.90 kcal/mol; Ki = 298.01 nM) and 14-3-3 protein (ΔG = −6.85 kcal/mol; Ki = 9.46 µM). The in vivo tests showed that the Nrf2, FOXO3, MnSOD, and GPx mRNA expression was significantly different between the groups (p < 0.05). Meanwhile, T-SOD, MnSOD, GPx, and GSH activity were not significantly different between the groups (p > 0.05). Nrf2 was significantly correlated with FOXO3 as well as the T-SOD, MnSOD, and GPx activity, and FOXO3 was significantly correlated with the T-SOD, MnSOD, GPx, and GSH activity. Conclusions: In obese rats, coriander seeds tend to increase Nrf2 and FOXO3 expression, which is positively correlated with their downstream enzymatic and nonenzymatic antioxidant activity. This is possibly due to the interaction between the coriander seed phytoconstituents and protein inhibitors (Keap1 and 14-3-3), which contribute to the stability and nuclear mobilization of Nrf2 and FOXO3. Full article

Cucumber green mottle mosaic virus (CGMMV) represents a serious threat in the production of watermelon. Small RNAs facilitate a mechanism known as RNA interference (RNAi), which regulates gene expression. RNAi technology employs foreign double-stranded RNAs (dsRNAs) to target and reduce the expression levels of specific genes in plants by interfering with their mRNAs. In this study, watermelon plants were treated with dsRNAs of CGMMV MET, IR, and HEL fragments that had been generated in E. coli HT115. We investigated variations in several factors, including viral accumulation, virus-derived small interfering RNAs (vsiRNAs), and symptom severity. MET-dsRNA, IR-dsRNA and HEL-dsRNA dramatically decreased the symptoms of CGMMV in plants in the growth chamber test. Plants treated with viral-derived dsRNA showed a considerable decrease in both virus titers and vsiRNA levels. We also explored the mobility of spray-on dsRNA-derived long dsRNA and discovered that it could be identified in both inoculated leaves and the systemic leaves. IR-dsRNA outperformed MET-dsRNA and HEL-dsRNA in dsRNA therapy. Illumina sequencing of small RNAs from watermelon plants treated with IR-dsRNA and those that were not treated showed that the decreased accumulation of vsiRNAs was consistent with interference with CGMMV infection in systemic leaves. dsRNA-treated plants showed a higher level of 24-nt viral siRNA and lower level of 22-nt viral siRNA accumulation, while 22-nt viral siRNA predominated in untreated plants, indicating that dsRNA treatment improved DCL3 activity. In conclusion, our research provides deeper insights into the mechanism of antiviral RNA interference and confirms the effectiveness of applying dsRNA locally to enhance plant antiviral activity. Full article

The current studies examined very early events associated with activation and initiation of a human immune response after sham exposure or exposure to influenza virus (IAV) versus respiratory syncytial virus (RSV), focusing on the function of a critical accessory cell for lymphocyte responses. Calcium mobilization by monocytes/macrophages was rapid and marked in response to exposure to IAV but was muted in response to RSV. Monocytes/macrophages exposed to IAV showed markedly enhanced expression of Cox-2 mRNA measured soon after exposure, whereas exposure to RSV resulted in reduced expression (relative to control cells). In contrast, expression of the constitutively expressed 2.8 kb Cox-1 mRNA was relatively constant. The 72/74 kDa/pl 7.5 protein doublet (product of the Cox-2 gene) was identified in lysates of IAV-exposed monocytes/macrophages but not RSV-exposed monocytes/macrophages. The results demonstrate that human monocytes/macrophages show reduced responses to RSV, similar to previously demonstrated effects of RSV on lymphocyte responses. This relative lack of early responses may contribute substantially to the ability of RSV to re-infect individuals. Full article

Conidiation and stress tolerance are pivotal traits in entomopathogenic fungi, critically influencing their production costs and environmental tolerance. While the transcription factor high-mobility group protein (HMG), characterized by a conserved HMG-box domain, has been extensively studied for its role in sexual development, its functions in entomopathogenic fungi remain largely unexplored. This study employed gene knockout to investigate the role of MaHMG in Metarhizium acridum. The deletion of MaHMG delayed conidiation initiation and caused a highly significant 58% reduction in conidial yield versus that of the wild type (WT) after 15 days. Furthermore, the conidiation pattern on microcycle induction medium (SYA) shifted from microcycle to normal conidiation. The ΔMaHMG mutant exhibited decreased conidial germination rates and markedly reduced tolerance following UV-B irradiation and heat-shock treatments, alongside increased sensitivity to the cell wall perturbant calcofluor white (CFW). RNA-seq analysis during this conidiation shift identified 88 differentially expressed genes (DEGs), with functional annotation implicating their predominant association with hyphal development, cell wall biogenesis, cell cycle progression, and conidiation. In conclusion, MaHMG functions as a critical positive regulator governing both conidiation and stress tolerance in M. acridum, underscoring its fundamental role in fungal biology and potential as a target for enhancing biocontrol agent performance. Full article

Background: Respiratory viral infections such as influenza, COVID-19, and respiratory syncytial virus (RSV) are considered as major public health threats in Africa. Despite global advancements in vaccine development, persistent inequities in access, delivery infrastructure, and public trust limit the continent’s capacity to control these diseases effectively. This review aimed at providing insights on challenges, efforts, impacts, and opportunities for the future related to vaccination against respiratory viral infections in Africa. Methods: This narrative review synthesizes the peer-reviewed literature and global health reports to examine vaccination efforts against respiratory viruses in Africa. The analysis focuses on disease burden, vaccine coverage, barriers to uptake, enabling factors, progress in local vaccine production, and strategies for integrating vaccines into national immunization programs (NIPs). Results: Respiratory vaccines have significantly reduced hospitalizations and mortality among high-risk groups in African countries. Nonetheless, key challenges, including limited cold chain capacity, vaccine hesitancy, donor-reliant supply chains, and under-resourced health systems, continue to undermine vaccine delivery. Successful interventions include community mobilization, use of mobile health technologies, and leveraging existing immunization platforms. Emerging initiatives in local vaccine manufacturing, including Rwanda’s modular mRNA facility and Senegal’s Institut Pasteur, signal a shift toward regional self-reliance. Conclusions: Maximizing the impact of respiratory vaccines in Africa requires a multifaceted strategy: integrating vaccines into NIPs, strengthening domestic production, expanding cold chain and digital infrastructure, and addressing sociocultural barriers through community-driven communication. These efforts are essential to achieving vaccine equity, health resilience, and pandemic preparedness across the continent. Full article

Nucleolin (NCL), an RNA-binding protein which regulates critical cellular processes, is frequently dysregulated in human cancers, including breast cancer, making it an attractive therapeutic target. However, molecular details of the RNA-NCL interaction have not been investigated yet. A tRNA fragment named tRF3E, displaying tumor suppressor roles in breast cancer, was found to bind NCL with high affinity displacing NCL-controlled transcripts. Here, we investigated the determinants and cooperativity of tRF3E-NCL interaction by Electrophoretic Mobility Shift Assays and in silico docking analysis, using wild-type or mutated tRF3E. We found that NCL, through its RNA-binding domains (RBD1–2 and RBD3–4), binds simultaneously two tRF3E molecules, giving rise to an energetically favored complex. Instead, a mutant form of tRF3E (M19–24), in which the NCL recognition element in position 19–24 has been disrupted, contacts NCL exclusively at RBD3–4, causing the loss of cooperativity among RBDs. Importantly, when expressed in MCF7 breast cancer cells, tRF3E significantly reduced cell proliferation and colony formation, confirming its role as tumor suppressor, but tRF3E functional properties were lost when the 19–24 motif was mutated, suggesting that cooperativity among multiple domains is required for the NCL-mediated tRF3E antitumor function. This study sheds light on the dynamic of RNA-NCL interaction and lays the foundations for using tRF3E as a promising NCL-targeted biodrug candidate. Full article

As life expectancy increases, muscle atrophy, characterized by a decline in muscle mass and strength that can impair mobility, has become a growing concern, highlighting the potential of protein supplementation as a promising intervention strategy. A horse meat hydrolysate, with a molecular weight of less than 3 kDa, derived from m. biceps femoris and produced using the food-grade enzyme Alcalase^® (A4 < 3kDa) was evaluated for its efficacy in mitigating dexamethasone-induced muscle atrophy, a widely accepted model for studying catabolic muscle loss. Administered orally to C57BL/6 mice at dosages of 200 mg/kg or 500 mg/kg body weight for 35 days, A4 < 3kDa effectively countered the weight loss induced by dexamethasone in the whole body, quadriceps, tibialis anterior, and gastrocnemius muscles. Moreover, it increased muscle fiber cross-sectional area and grip strength. These effects were attributed to increased protein synthesis via the protein kinase B (AKT)/forkhead box O3 (FoxO3a)/mammalian target of rapamycin (mTOR) signaling pathway. A4 < 3kDa augmented the phosphorylation of key components of the signaling pathways associated with muscle atrophy, resulting in reduced mRNA expression of Atrogin-1 and MuRF-1. These findings demonstrate the potential of A4 < 3kDa as a functional food ingredient for preventing muscle atrophy. Full article

The transition period is defined as 3 weeks around parturition, involving the rapid increase in the energy demand, promoting adipose mobilization and non-esterified fatty acid (NEFA) release. High NEFA levels might cause oxidative stress and associated health risks, including the disruption of the immune capability of peripheral leukocytes. Nutrient supplementation of choline, which improves cellular lipid metabolism and controls lipid oxidation, potentially maintains the integrity of peripheral leukocytes and alleviates the impacts of increased NEFAs. This study investigated the effects of choline on bovine peripheral blood leukocytes (PBLs) treated with high levels of NEFAs. Peripheral blood mononuclear cells (PBMCs) and polymorphonuclear leukocytes (PMNs) were isolated from dry cows, and treated with 1 mM NEFA in combination with 0, 4, or 12 μM choline. The expression of pro-inflammatory cytokines and oxidative stress indicators was determined. This study demonstrates that 1 mM NEFA induces lipid oxidation and pro-inflammatory cytokine expression in PBLs. Supplementation with 4 μM and 12 μM choline significantly reduced NEFA-induced lipid oxidation; however, it did not affect pro-inflammatory cytokine mRNA expression. In conclusion, choline supplementation may help alleviate NEFA-induced oxidative stress in bovine peripheral blood leukocytes, highlighting its potential as a functional supplement during the transition period. However, it had no observable effect on mitigating pro-inflammatory responses, indicating that additional strategies may be needed to address NEFA-induced immune activation. Full article

Grafting significantly enhances plant quality, including stress resistance and fruit quality. We previously found that grafting watermelon onto pumpkin can alter the metabolite content, but the involvement of mobile RNA was unclear. Here, we established and comprehensively analyzed mobile mRNA (mb-mRNA) profiles, transcriptomes, and metabolomes between the rootstock (pumpkin) and scion (watermelon). A total of 834 mobile RNAs were identified in the pulp and stem of pumpkin-grafted watermelon. GO (Gene Ontology) and KO (Kyoto Encyclopedia of Genes and Genomes Orthology) analyses revealed photosynthesis- and carbon fixation-related mobile RNAs (e.g., Photosystem II D2, P700 chlorophyll a apoprotein) in the watermelon pulp and cell division-related mobile RNAs in the stem. Additionally, transcription factors like MADS and DNAJ exhibited mobility. The secondary structure prediction of the MADS-box transcription factor (CmoCh20G002790) showed multiple loop structures (e.g., internal and hairpin loops) related to its mobility. An integrated analysis of transcript and metabolite profiles indicated that photosynthesis-related products are regulated not only by the scion’s own RNA but also by mb-mRNA synthesized by the rootstock. This research advances our understanding of grafting’s molecular mechanisms and provides insights for improving crop quality and sustainability in agriculture. Full article

Background and Objectives: Aging-related bone loss still lacks interventions. As bone marrow-derived mesenchymal stem cells (BMSCs) undergo aging, R-loop-induced DNA replication stress impairs the osteogenic ability of BMSCs. High-mobility group A-2 (Hmga2) acts as a DNA-binding protein, and the understanding of its underlying mechanisms is crucial for developing effective preventive and therapeutic strategies. Materials and Methods: Aging mice were used as the experimental model, and mouse BMSCs were isolated from their femurs. Hmga2 was achieved through specific gene delivery methods. R-loop formation was detected using dot blotting, chromatin immunoprecipitation (ChIP), and DNA–RNA immunoprecipitation (DRIP) assays. Osteogenic differentiation was evaluated. Results: R-loops were highly accumulated in aging BMSCs. Notably, the key regulator Hmga2 reversed the accumulation of R-loops in aging BMSCs. Hmga2 overexpression significantly decreased the senescence and improved the osteogenic differentiation of aging mBMSCs. Mechanistically, R-loop-forming sequence (RLFS) regions were confirmed in key osteogenesis-related genes, including runt-related transcription factor 2 (Runx2). Hmga2 bound to the RLFS region of Runx2 and promoted its expression by reducing the R-loop level. More, Hmga2 treatment delivered via the AAV system effectively decreased bone loss in aging mice and increased the serum bone turnover biomarkers and collagen remodeling. Conclusions: Our study demonstrates that Hmga2 acts as an activator of aging BMSCs, significantly promoting their osteogenic ability by eliminating the aging-induced DNA replication stress caused by R-loops. Our findings provide new insights into the mechanisms of aging-related bone loss, suggesting that Hmga2 may be a new strategy for alleviating the bone loss phenotype in aging individuals. Full article

Hepatocellular carcinoma (HCC) is a lethal malignancy associated with drug resistance, resulting in a poor prognosis. High mobility group box 1 (HMGB1) is a chromatin-binding protein that regulates HCC progression. The overexpression of HMGB1 has been found to promote tumorigenesis and drug resistance. In this study, we aimed to investigate the role of HMGB1 expression in tumorigenesis and metastasis and its impact on sorafenib and oxaliplatin resistance. Tissue samples from patients with HCC (n = 48) were subjected to immunohistochemistry. The expression of HMGB1 was correlated with clinical pathology parameters. Moreover, the HCC cell line HuH-7 was used to study the regulatory effect of HMGB1 on cell proliferation, cell adhesion, migration, and invasion by using the siRNA (small interfering RNA) silencing method. Furthermore, drug challenges were performed to determine the effect of HMGB1 on the sensitivity to chemotherapeutic drugs (sorafenib and oxaliplatin). HMGB1 was significantly overexpressed in tumor tissues, highlighted by the expression increment in patients with M1 advanced metastasis tumors with immunoreactivity scores 2.61 and 6.50 for adjacent and tumor tissues, respectively (p-values = 0.0035). The involved mechanisms were then described through the suppression of HCC cell adhesion, migration, and invasion by HMGB1 silencing. Notably, the inhibition of HMGB1 expression promoted sorafenib/oxaliplatin sensitivity in the HCC cell line by increasing the cell toxicity by about 13–18%. Our study demonstrated that HMGB1 shows potential as a promising biomarker and a target for HCC treatment that is involved in tumorigenesis, metastasis, and chemo-drug resistance. Full article

The spiro compound, 5,5′-dimethoxy-1,3-bis(3-(trifluoromethyl)phenyl)-3,3a-dihydro-1H-spiro[cyclopenta[a]indene-2,2′-indene]-1′,8(3′H,8aH)-dione (4), was synthesized and identified by NMR spectroscopy, mass spectrometry, and X-ray crystallography. Compound 4, C₃₆H₂₆F₆O₄, was crystallized in the triclinic space group P-1with the cell parameters a = 8.8669(5) Å, b = 10.5298(8) Å, c = 17.0135(11) Å, α = 91.396(2)°, β = 90.490(2)°, γ = 109.235°, V = 1499.14(17) ų, Z = 2. In an asymmetric unit, two molecules are packed by short contacts to form an inversion dimer. The molecules are linked into chains along the a- and b-axis directions by additional short contacts in the crystal. Compound 4 was synthesized by the dimerization of (E)-5-methoxy-2-(3-(trifluoromethyl)benzylidene)-2,3-dihydro-1H-inden-1-one (3). (E)-5-Methoxy-2-(3-methoxybenzylidene)-2,3-dihydro-1H-inden-1-one (5), one of the analogs of compound 3, was compared with compound 4 based on in vitro experiments, DFT calculations, and an in silico docking study. The HOMO/LUMO energy difference and binding energy difference between the two compounds are consistent with the results obtained from an in vitro assay where 4 showed a better effect than 5. To evaluate the biological activity of 4, we examined its inhibitory effects on Early Growth Respone-1 (EGR-1)-regulated gene expression in HaCaT keratinocytes. Treatment of cells with 4 reduced interleukin-4 (IL-4)-induced thymic stromal lymphopoietin (TSLP) mRNA levels, as revealed by reverse transcription-polymerase chain reaction and quantitative real-time PCR. Furthermore, the electrophoretic mobility shift assay demonstrated that 4 inhibited IL-4-induced DNA binding of EGR-1 to the promoter region of the TSLP gene. Full article

Grafting is widely used as an effective strategy to enhance tolerance to biotic and abiotic stresses and improve fruit quality in horticultural crops. However, the molecular mechanisms of transcription and the regulatory functions in response to drought stress of mobile mRNAs remain poorly understood. In this study, we developed a grafting system based on the “one grafted plant—three samples” approach using the cultivated tomato/Solanum pennellii (Heinz 1706/LA 0716) heterografting system. A bioinformatics pipeline was developed based on RNA-seq to identify mobile mRNAs in the heterografting systems. A total of 61 upwardly and 990 downwardly mobile mRNAs were identified. Furthermore, we found that the mobility of mRNAs was not correlated with their abundance. The functional annotation and enrichment analysis indicated that mobile mRNAs were mainly involved in RNA binding, photosynthesis, photosystem, response to heat, and translation processes, and ultimately increased the drought tolerance of grafted plants. In addition, we also analyzed the RNA-binding proteins (RBPs) of downwardly mobile mRNAs and found that RBPs were conserved among species. Further, mobile mRNAs may be degraded during transportation. This study provides a pipeline for detecting mobile mRNAs in plant heterografting systems and offers new insights into future studies on long-distance mRNAs transport and regulatory mechanisms involved in drought stress responses. Full article

Increasingly popular, recreational diving is a physical activity that takes place under extreme environmental conditions, which include hyperoxia, hyperbaria and exposure to cold water. The effects of these factors on the human body induce increased levels of reactive oxygen and nitrogen species in divers’ bodies, which may modulate damage-associated molecular pattern (DAMPs), their receptors and the antioxidant response. This study involved 21 divers who descended to a depth of 40 metres. Determinations of selected intracellular DAMPs (high-mobility group box protein 1,HMGB1, S100 calcium-binding proteins A9 and A8, S100A8 and S100A9, heat shock protein family A member 1A, HSPA1A (Hsp70), heat shock protein family B, (small) member 1, HSPB1(Hsp27), thioredoxin, TXN), their receptors (Toll-like receptor 4, TLR4 and receptors for advanced glycation end products, RAGE), nuclear factor-κB (NF-κB) and antioxidant defence markers were performed before, after and 1 h after the dive. A significant transient reduction in HMGB1 expression was observed immediately after the dive at both the mRNA and protein levels. We noted an increase in S100A9 expression, which occurred 1 h post-dive compared to the post-dive time point, and a post-dive decrease in TLR4 expression only at the mRNA level. Diving also influenced the expression of genes encoding key enzymes associated with glutathione synthesis, (glutamate-cysteine ligase, catalytic subunit, GCLC and glutathione synthetase, GSS), and reduced plasma glutathione levels. However, no significant changes were observed in the expression of NF-κB, nitric oxide synthase 2 (NOS2) or circulating DAMP receptors (TLR4 and RAGE). The findings suggest an adaptive response to diving-induced oxidative stress, which appears to be a protective mechanism against an excessive inflammatory response. To our knowledge, this is the first study to analyse the role of intracellular DAMPs in recreational divers. Full article

The fifth generation (5G) of mobile communications promotes human exposure to electromagnetic fields exploiting the 3.5 GHz frequency band. We analyzed behaviors, cognitive functions, and gene expression in mice submitted to asymmetrical head exposure to a 5G-modulated 3.5 GHz signal. The exposures were applied for 1 h daily, 5 days per week over a six-week period, at a specific absorption rate (SAR) averaging 0.19 W/kg over the brain. Locomotor activities in an open field, object location, and object recognition memories were assessed repeatedly after four weeks of exposure and did not reveal any significant effect on the locomotion/exploration, anxiety level, or memory processes. mRNA profiling was performed at the end of the exposure period in two symmetrical areas of the right and left cerebral cortex, in which the SAR values were 0.43 and 0.14 W/kg, respectively. We found significant changes in the expression of less than 1% of the expressed genes, with over-representations of genes related to glutamatergic synapses. The right cortical area differed from the left one by an over-representation of responsive genes encoded by the mitochondrial genome. Our data show that repeated head exposures to a 5G-3.5 GHz signal can trigger mild transcriptome alterations without changes in memory capacities or emotional state. Full article