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International Journal of Molecular... Jun 2024Bakanae disease (BD), caused by the fungal pathogen , is a serious threat to rice production worldwide. Breeding elite rice varieties resistant to BD requires the...
Bakanae disease (BD), caused by the fungal pathogen , is a serious threat to rice production worldwide. Breeding elite rice varieties resistant to BD requires the identification of resistance genes. Previously, we discovered a resistant quantitative trait locus (QTL), , in a Korean rice variety, Nampyeong. In this study, we fine-mapped with a Junam/Nampyeong BCF population and delimited its location to a 37.1 kb region on chromosome 1. Complementation experiments with seven candidate genes in this region revealed that is the gene for . This gene encodes a protein with a typical leucine-rich repeat (LRR) receptor-like protein structure. RNA-sequencing-based transcriptomic analysis revealed that FfR1 induces the transcription of defense genes, including lignin and terpenoid biosynthesis genes, pathogenesis-related genes, and thionin genes. These results may facilitate investigations into the molecular mechanisms underlying BD resistance, including molecular patterns of interacting with FfR1 and players working in signal transduction pathways downstream of FfR1, and the breeding of new BD-resistant varieties by providing a BD resistance gene with its precise selection marker. This will contribute to efficient control of BD, which is becoming more prevalent according to temperature rises due to climate change.
Topics: Oryza; Quantitative Trait Loci; Disease Resistance; Plant Diseases; Fusarium; Chromosome Mapping; Cloning, Molecular; Plant Proteins; Gene Expression Regulation, Plant; Chromosomes, Plant
PubMed: 38892403
DOI: 10.3390/ijms25116214 -
International Journal of Molecular... Jun 2024Post-translational modifications (PTMs) are essential for regulating protein functions, influencing various fundamental processes in eukaryotes. These include, but are... (Review)
Review
Post-translational modifications (PTMs) are essential for regulating protein functions, influencing various fundamental processes in eukaryotes. These include, but are not limited to, cell signaling, protein trafficking, the epigenetic control of gene expression, and control of the cell cycle, as well as cell proliferation, differentiation, and interactions between cells. In this review, we discuss protein PTMs that play a key role in the malaria parasite biology and its pathogenesis. Phosphorylation, acetylation, methylation, lipidation and lipoxidation, glycosylation, ubiquitination and sumoylation, nitrosylation and glutathionylation, all of which occur in malarial parasites, are reviewed. We provide information regarding the biological significance of these modifications along all phases of the complex life cycle of spp. Importantly, not only the parasite, but also the host and vector protein PTMs are often crucial for parasite growth and development. In addition to metabolic regulations, protein PTMs can result in epitopes that are able to elicit both innate and adaptive immune responses of the host or vector. We discuss some existing and prospective results from antimalarial drug discovery trials that target various PTM-related processes in the parasite or host.
Topics: Protein Processing, Post-Translational; Life Cycle Stages; Humans; Animals; Protozoan Proteins; Plasmodium; Malaria; Host-Parasite Interactions
PubMed: 38892332
DOI: 10.3390/ijms25116145 -
International Journal of Molecular... May 2024Petanin, an acylated anthocyanin from the Solanaceae family, shows potential in tyrosinase inhibitory activity and anti-melanogenic effects; however, its mechanism...
Petanin, an acylated anthocyanin from the Solanaceae family, shows potential in tyrosinase inhibitory activity and anti-melanogenic effects; however, its mechanism remains unclear. Therefore, to investigate the underlying mechanism of petanin's anti-melanogenic effects, the enzyme activity, protein expression and mRNA transcription of melanogenic and related signaling pathways in zebrafish using network pharmacology, molecular docking and molecular dynamics simulation were combined for analysis. The results showed that petanin could inhibit tyrosinase activity and melanogenesis, change the distribution and arrangement of melanocytes and the structure of melanosomes, reduce the activities of catalase (CAT) and peroxidase (POD) and enhance the activity of glutathione reductase (GR). It also up-regulated JNK phosphorylation, inhibited ERK/RSK phosphorylation and down-regulated CREB/MITF-related protein expression and mRNA transcription. These results were consistent with the predictions provided through network pharmacology and molecular docking. Thus, petanin could inhibit the activity of tyrosinase and the expression of tyrosinase by inhibiting and negatively regulating the tyrosinase-related signaling pathway ERK/CREB/MITF through p-JNK. In conclusion, petanin is a good tyrosinase inhibitor and anti-melanin natural compound with significant market prospects in melanogenesis-related diseases and skin whitening cosmetics.
Topics: Animals; Zebrafish; Melanins; Molecular Docking Simulation; Phosphorylation; MAP Kinase Signaling System; Signal Transduction; Cyclic AMP Response Element-Binding Protein; Monophenol Monooxygenase; Microphthalmia-Associated Transcription Factor; Melanocytes
PubMed: 38892131
DOI: 10.3390/ijms25115939 -
International Journal of Molecular... May 2024The central dogma treats the ribosome as a molecular machine that reads one mRNA codon at a time as it adds each amino acid to its growing peptide chain. However, this...
The central dogma treats the ribosome as a molecular machine that reads one mRNA codon at a time as it adds each amino acid to its growing peptide chain. However, this and previous studies suggest that ribosomes actually perceive pairs of adjacent codons as they take three-nucleotide steps along the mRNA. We examined GNN codons, which we find are surprisingly overrepresented in eukaryote protein-coding open reading frames (ORFs), especially immediately after NNU codons. Ribosome profiling experiments in yeast revealed that ribosomes with NNU at their aminoacyl (A) site have particularly elevated densities when NNU is immediately followed (3') by a GNN codon, indicating slower mRNA threading of the NNU codon from the ribosome's A to peptidyl (P) sites. Moreover, if the assessment was limited to ribosomes that have only recently arrived at the next codon, by examining 21-nucleotide ribosome footprints (21-nt RFPs), elevated densities were observed for multiple codon classes when followed by GNN. This striking translation slowdown at adjacent 5'-NNN GNN codon pairs is likely mediated, in part, by the ribosome's CAR surface, which acts as an extension of the A-site tRNA anticodon during ribosome translocation and interacts through hydrogen bonding and pi stacking with the GNN codon. The functional consequences of 5'-NNN GNN codon adjacency are expected to influence the evolution of protein coding sequences.
Topics: Protein Biosynthesis; Codon; Ribosomes; Open Reading Frames; RNA, Messenger; RNA, Transfer; Saccharomyces cerevisiae; Anticodon
PubMed: 38892101
DOI: 10.3390/ijms25115914 -
International Journal of Molecular... May 2024Keloids, marked by abnormal cellular proliferation and excessive extracellular matrix (ECM) accumulation, pose significant therapeutic challenges. Ethyl pyruvate (EP),...
Keloids, marked by abnormal cellular proliferation and excessive extracellular matrix (ECM) accumulation, pose significant therapeutic challenges. Ethyl pyruvate (EP), an inhibitor of the high-mobility group box 1 (HMGB1) and TGF-β1 pathways, has emerged as a potential anti-fibrotic agent. Our research evaluated EP's effects on keloid fibroblast (KF) proliferation and ECM production, employing both in vitro cell cultures and ex vivo patient-derived keloid spheroids. We also analyzed the expression levels of ECM components in keloid tissue spheroids treated with EP through immunohistochemistry. Findings revealed that EP treatment impedes the nuclear translocation of HMGB1 and diminishes KF proliferation. Additionally, EP significantly lowered mRNA and protein levels of collagen I and III by attenuating TGF-β1 and pSmad2/3 complex expression in both human dermal fibroblasts and KFs. Moreover, metalloproteinase I (MMP-1) and MMP-3 mRNA levels saw a notable increase following EP administration. In keloid spheroids, EP induced a dose-dependent reduction in ECM component expression. Immunohistochemical and western blot analyses confirmed significant declines in collagen I, collagen III, fibronectin, elastin, TGF-β, AKT, and ERK 1/2 expression levels. These outcomes underscore EP's antifibrotic potential, suggesting its viability as a therapeutic approach for keloids.
Topics: Humans; Keloid; Fibroblasts; Pyruvates; Spheroids, Cellular; Matrix Metalloproteinase 1; Transforming Growth Factor beta1; HMGB1 Protein; Collagen; Cell Proliferation; Cells, Cultured; Matrix Metalloproteinase 3; Extracellular Matrix; Collagen Type I; Smad2 Protein; Smad3 Protein; Up-Regulation; Male
PubMed: 38892032
DOI: 10.3390/ijms25115844 -
International Journal of Molecular... May 2024Soybean, a major source of oil and protein, has seen an annual increase in consumption when used in soybean-derived products and the broadening of its cultivation range....
Soybean, a major source of oil and protein, has seen an annual increase in consumption when used in soybean-derived products and the broadening of its cultivation range. The demand for soybean necessitates a better understanding of the regulatory networks driving storage protein accumulation and oil biosynthesis to broaden its positive impact on human health. In this study, we selected a chromosome segment substitution line (CSSL) with high protein and low oil contents to investigate the underlying effect of donor introgression on seed storage through multi-omics analysis. In total, 1479 differentially expressed genes (DEGs), 82 differentially expressed proteins (DEPs), and 34 differentially expressed metabolites (DEMs) were identified in the CSSL compared to the recurrent parent. Based on Gene Ontology (GO) term analysis and the Kyoto Encyclopedia of Genes and Genomes enrichment (KEGG), integrated analysis indicated that 31 DEGs, 24 DEPs, and 13 DEMs were related to seed storage functionality. Integrated analysis further showed a significant decrease in the contents of the seed storage lipids LysoPG 16:0 and LysoPC 18:4 as well as an increase in the contents of organic acids such as L-malic acid. Taken together, these results offer new insights into the molecular mechanisms of seed storage and provide guidance for the molecular breeding of new favorable soybean varieties.
Topics: Glycine max; Seeds; Gene Expression Regulation, Plant; Chromosomes, Plant; Gene Regulatory Networks; Plant Breeding; Gene Expression Profiling; Gene Ontology; Transcriptome; Multiomics
PubMed: 38891802
DOI: 10.3390/ijms25115614 -
Plants (Basel, Switzerland) May 2024This study aimed to reveal the impact of MeJA and ZnSO treatments on the physiological metabolism of barley seedlings and the content of phenolic acid. The results...
This study aimed to reveal the impact of MeJA and ZnSO treatments on the physiological metabolism of barley seedlings and the content of phenolic acid. The results showed that MeJA (100 μM) and ZnSO (4 mM) treatments effectively increased the phenolic acid content by increasing the activities of phenylalanine ammonia-lyase and cinnamate-4-hydroxylase (PAL) and cinnamic acid 4-hydroxylase (C4H) and by up-regulating the expression of genes involved in phenolic acid synthesis. As a result of the MeJA or ZnSO treatment, the phenolic acid content increased by 35.3% and 30.9% at four days and by 33.8% and 34.5% at six days, respectively, compared to the control. Furthermore, MeJA and ZnSO treatments significantly increased the malondialdehyde content, causing cell membrane damage and decreasing the fresh weight and seedling length. Barley seedlings responded to MeJA- and ZnSO-induced stress by increasing the activities of antioxidant enzymes and controlling their gene expression levels. Meanwhile, MeJA and ZnSO treatments significantly upregulated , , and genes in barley seedlings. This suggested that Ca may be the signaling molecule that promotes phenolic acid synthesis under MeJA and ZnSO treatment. This study deepens the understanding of the phenolic acid enrichment process in barley seedlings under MeJA and ZnSO treatments.
PubMed: 38891320
DOI: 10.3390/plants13111512 -
Foods (Basel, Switzerland) May 2024Exopolysaccharides are natural macromolecular bioactive substances produced by lactic acid bacteria. With their unique physiological activity and structural... (Review)
Review
Exopolysaccharides are natural macromolecular bioactive substances produced by lactic acid bacteria. With their unique physiological activity and structural characteristics, they are gradually showing broad application prospects in the food and pharmaceutical industries. Exopolysaccharides have various biological functions, such as exerting antioxidant and anti-tumor activities and regulating gut microbiota. Meanwhile, as a food additive, exopolysaccharides can significantly enhance the taste and quality of food, bringing consumers a better eating experience. In the field of medicine, exopolysaccharides have been widely used as drug carriers due to their non-toxic properties and good biocompatibility. This article summarizes the biological activities of exopolysaccharides produced by lactic acid bacteria, their synthesis, and their applications in food and pharmaceutical industries, aiming to promote further research and development in this field.
PubMed: 38890849
DOI: 10.3390/foods13111621 -
Journal of Nanobiotechnology Jun 2024Incomplete radiofrequency ablation (iRFA) in hepatocellular carcinoma (HCC) often leads to local recurrence and distant metastasis of the residual tumor. This is closely...
BACKGROUND
Incomplete radiofrequency ablation (iRFA) in hepatocellular carcinoma (HCC) often leads to local recurrence and distant metastasis of the residual tumor. This is closely linked to the development of a tumor immunosuppressive environment (TIME). In this study, underlying mechanisms and potential therapeutic targets involved in the formation of TIME in residual tumors following iRFA were explored. Then, TAK-981-loaded nanocomposite hydrogel was constructed, and its therapeutic effects on residual tumors were investigated.
RESULTS
This study reveals that the upregulation of small ubiquitin-like modifier 2 (Sumo2) and activated SUMOylation is intricately tied to immunosuppression in residual tumors post-iRFA. Both knockdown of Sumo2 and inhibiting SUMOylation with TAK-981 activate IFN-1 signaling in HCC cells, thereby promoting dendritic cell maturation. Herein, we propose an injectable PDLLA-PEG-PDLLA (PLEL) nanocomposite hydrogel which incorporates self-assembled TAK-981 and BSA nanoparticles for complementary localized treatment of residual tumor after iRFA. The sustained release of TAK-981 from this hydrogel curbs the expansion of residual tumors and notably stimulates the dendritic cell and cytotoxic lymphocyte-mediated antitumor immune response in residual tumors while maintaining biosafety. Furthermore, the treatment with TAK-981 nanocomposite hydrogel resulted in a widespread elevation in PD-L1 levels. Combining TAK-981 nanocomposite hydrogel with PD-L1 blockade therapy synergistically eradicates residual tumors and suppresses distant tumors.
CONCLUSIONS
These findings underscore the potential of the TAK-981-based strategy as an effective therapy to enhance RFA therapy for HCC.
Topics: Carcinoma, Hepatocellular; Liver Neoplasms; Animals; Hydrogels; Nanocomposites; Humans; Mice; Radiofrequency Ablation; Sumoylation; Cell Line, Tumor; Male
PubMed: 38890737
DOI: 10.1186/s12951-024-02579-1 -
Microbial Cell Factories Jun 2024Human lysozyme (hLYZ) is a natural antibacterial protein with broad applications in food and pharmaceutical industries. Recombinant production of hLYZ in Komagataella...
BACKGROUND
Human lysozyme (hLYZ) is a natural antibacterial protein with broad applications in food and pharmaceutical industries. Recombinant production of hLYZ in Komagataella phaffii (K. phaffii) has attracted considerable attention, but there are very limited strategies for its hyper-production in yeast.
RESULTS
Here through Atmospheric and Room Temperature Plasma (ARTP)-based mutagenesis and transcriptomic analysis, the expression of two genes MYO1 and IQG1 encoding the cytokinesis core proteins was identified downregulated along with higher hLYZ production. Deletion of either gene caused severe cytokinesis defects, but significantly enhanced hLYZ production. The highest hLYZ yield of 1,052,444 ± 23,667 U/mL bioactivity and 4.12 ± 0.11 g/L total protein concentration were obtained after high-density fed-batch fermentation in the Δmyo1 mutant, representing the best production of hLYZ in yeast. Furthermore, O-linked mannose glycans were characterized on this recombinant hLYZ.
CONCLUSIONS
Our work suggests that cytokinesis-based morphology engineering is an effective way to enhance the production of hLYZ in K. phaffii.
Topics: Muramidase; Recombinant Proteins; Saccharomycetales; Humans; Fermentation; Cytokinesis; Metabolic Engineering; Batch Cell Culture Techniques
PubMed: 38890717
DOI: 10.1186/s12934-024-02434-w