Search Results (124)

The Mi-1 gene of tomato is responsible for the resistance of certain genotypes to root-knot nematodes or RKN (Meloidogyne spp.) and other harmful organisms such as aphids or whiteflies, in a complex cascade of transcriptional changes in which other tomato genes are also involved. The objective of this study was to gain a deeper understanding of the Mi-1-mediated resistance of tomato to Meloidogyne javanica using oligonucleotide microarrays to identify additional plant genes involved in the compatible or incompatible tomato/nematode interactions. Microarray analysis was selected as it has been widely used to identify genes involved in plant resistance to pests and pathogens. In a first phase of the present work, the roots of uninfested tomato plants were analyzed, comparing the transcriptional profiles of susceptible (Moneymaker) and resistant (Motelle) cultivars. In Motelle, 180 transcripts were more expressed than in Moneymaker and only 44 transcripts showed lower expression. Motelle showed higher activity in salicylic, jasmonic and ethylene pathways, while the GAI protein was strongly repressed compared to Moneymaker. These and other basal differences provided valuable information on candidate genes associated with the presence of the Mi-1 gene in Motelle. Subsequent infection by M. javanica triggered an intense transcriptional reprograming that increased over time throughout both compatible (Moneymaker) and incompatible (Motelle) interactions, with scarce genes common to both interactions. At the early phase of infection (2 dpi), genes for the cell wall, hormones, RNA, stress, and transport were up-regulated in the compatible interaction, and signaling, protein, and redox genes were down-regulated; in the incompatible interaction, protease inhibitors were up-regulated, and hormone and RNA genes were down-regulated. Later (12 dpi), genes for hormones, the cell wall, RNA, stress, defense, and development were up-regulated in the compatible interaction, while transport and some stress/defense genes were down-regulated; the incompatible interaction showed mixed regulation within hormone, stress, and defense genes. Full article

Background: SARS-CoV-2 infection during pregnancy has been associated with systemic inflammatory responses and placental pathology; however, the molecular mechanisms underlying placental involvement remain incompletely understood. The endocannabinoid system plays a critical role in placental development, immune regulation, and vascular homeostasis. Materials and Methods: Placental tissues were obtained from 20 healthy pregnant women and 20 women with confirmed SARS-CoV-2 infection who had recovered by the time of delivery. Demographic and laboratory parameters were recorded. Histopathological evaluation was performed using hematoxylin and eosin staining. Immunohistochemical analysis of cannabinoid receptor 1 (CNR1) and cannabinoid receptor 2 (CNR2) expression was conducted, supported by quantitative digital image analysis using QuPath. Network-based protein–protein interaction and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore potential molecular mechanisms. Results: COVID-19-positive placentas exhibited prominent histopathological alterations, including increased fibrinoid deposition, syncytial knot formation, vascular congestion, and intervillous inflammatory cell infiltration. Systemic inflammatory and coagulation markers, particularly neutrophil percentage, C-reactive protein, D-dimer, and fibrinogen levels, were significantly elevated in the COVID-19 group. CNR1 and CNR2 expressions were markedly increased across multiple placental compartments, including decidual cells, trophoblastic layers, syncytial knots, and Hofbauer cells. Quantitative digital analysis confirmed significant upregulation of both receptors. Bioinformatic analysis revealed enrichment of endocannabinoid signaling, cAMP-related pathways, and inflammatory mediator regulation of TRP channels. Conclusions: The findings indicate that SARS-CoV-2 infection is associated with coordinated inflammatory, structural, and molecular alterations in the placenta. Upregulation of CB1 and CB2 suggests an active involvement of the endocannabinoid system in placental immune and vascular responses to COVID-19, highlighting its potential relevance for understanding placental pathology associated with maternal viral infections Full article

Frequent strain degeneration during subcultivation, characterized by impaired sporulation and fruiting body formation, represents a major constraint in fungal agricultural production. Our study systematically investigated two naturally degenerated Lentinula edodes strains classified as abortive (Abt: L808-13, L808-14) and malformed (Abn: L808-18) fruiting-body phenotypes, through comprehensive phenotypic characterization, enzymatic profiling, thermotolerance assessment, and transcriptomic analysis. While vegetative growth remained unaffected, degenerated strains exhibited premature hyphal knotting, significantly reduced thermotolerance, and Abn-specific suppression of carboxymethyl cellulase (CMCase) activity. Comparative transcriptomics revealed 1239 and 582 differentially expressed genes (DEGs) in Abt and Abn groups, respectively, accompanied by a global dysregulation in carbohydrate catabolism, phospholipid metabolism, and redox homeostasis. Furthermore, protein–protein interaction (PPI) networks and RT-qPCR data highlighted 12 core hub genes enriched in glycoside hydrolysis, cytochrome P450 signaling, and membrane lipid dynamics. These findings provide mechanistic insights into the molecular basis of fruiting body degeneration and establish a foundation for developing diagnostic indicators to screen for early-stage degeneration in industrial mushroom production. Full article

Background: Preeclampsia (PE) is a hypertensive disorder of pregnancy associated with oxidative stress and mitochondrial dysfunction. NRF1 and NRF2 are transcription factors that regulate mitochondrial activity and antioxidant defense. This study investigated their expression patterns in placentas from preeclamptic and severe preeclamptic pregnancies by immunohistochemical and bioinformatical methods. Methods: Placentas from 40 healthy controls, 40 PE, and 40 sPE patients were analyzed by histological and immunohistochemical techniques. Protein–protein interaction networks for NRF1, NRF2, and PE-related proteins were constructed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape software, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis performed via ShinyGO, with significance set at false discovery rate (FDR) < 0.05. Results: NRF1 expression was significantly decreased in PE and sPE groups compared to controls, with notably negative staining in syncytial knots and fibrinoid areas. Conversely, NRF2 expression significantly increased, showing intense positivity in syncytiotrophoblasts, stromal cells, and vascular structures. Pathway analysis revealed that decreased NRF1 expression was associated with glutathione metabolism, hypoxia inducible factor-1 (HIF-1) signaling, and AMP-Activated Protein Kinase (AMPK) signaling pathways. Increased NRF2 expression was associated predominantly with inflammatory and immune response pathways, including AGE-RAGE signaling and pathogen–response pathways. Conclusions: Differential expressions of NRF1 and NRF2 in preeclamptic placentas reflect distinct yet interconnected responses to oxidative stress and inflammation. These transcription factors have potential clinical relevance as biomarkers for PE severity assessment and as targets for future therapeutic interventions. Full article

Root-knot nematodes, known for their broad host range and the challenges associated with their control, cause significant losses in global agricultural productivity. The mitogen-activated protein kinase (MAPK) pathway amplifies signals through a phosphorylation cascade to regulate downstream transcription factors or effector proteins, which is essential for maintaining normal physiological functions in nematodes. This study presents a comprehensive characterization of the MAPK signaling cascade regulatory network in Meloidogyne incognita, elucidating the regulatory roles of Mi-let-60, Mi-lin-45, Mi-mek-2, and Mi-mpk-1 in host chemotaxis and egg hatching behavior. Importantly, RNAi-mediated silencing of Mi-mpk-1 resulted in a 17-fold increase in egg hatching rate and significantly impaired chemotactic responses while silencing of Mi-let-60 led to a marked reduction in root gall formation and egg mass production. These results not only confirmed the evolutionary conservation of this pathway but also identified a feedback regulation mechanism unique to parasitic nematodes. These findings provide valuable insights for future research on signal transduction pathways and the sustainable management of root-knot nematodes. Full article

Introduction: The contribution of SARS-CoV-2 infection to the severity of placental alterations in preeclampsia remains unclear. This study aimed to evaluate the morphological changes in placentas of women who experienced COVID-19 during pregnancy, with a focus on the presence or absence of preeclampsia. Materials and Methods: The study included placentas from: (1) patients with both COVID-19 during pregnancy and preeclampsia (n = 20, 2022); (2) patients with COVID-19 during pregnancy without preeclampsia (n = 20, 2022); (3) patients with preeclampsia but without COVID-19 (n = 5, 2019); (4) patients with physiological pregnancies without COVID-19 or gestational complications (n = 5, 2019). Histological and immunohistochemical examinations of the placentas were performed using antibodies against the SARS-CoV-2 spike protein, DPP4 (CD26), and VEGF. Results: Placentas from patients with both COVID-19 and preeclampsia demonstrated the most pronounced stromal and vascular alterations, including pseudo-infarctions and villous fibrosis. Chorangiosis, excessive fibrinoid deposition in the intervillous space, and accelerated villous maturation with an increased number of syncytial knots were more common in the preeclampsia groups, regardless of prior COVID-19 infection. Symptomatic forms of coronavirus infection were associated with more severe manifestations of malperfusion. Expression of the SARS-CoV-2 spike protein was detected in 78% of syncytiotrophoblast cells and 37% of decidual cells in 28 of 40 placentas from women with previous COVID-19, while its presence in the vascular endothelium, macrophages, and villous fibroblasts was focal, as was CD26 expression. VEGF expression did not differ significantly between patients with and without COVID-19. Conclusions: COVID-19 is associated with more pronounced stromal–vascular alterations in the placenta; however, not all of these changes are directly caused by the virus itself but rather reflect the severe course of preeclampsia. Inflammatory alterations are nonspecific for COVID-19, even though CD26 and the SARS-CoV-2 spike protein are detectable in nearly all placental structures, whereas VEGF levels remain comparable to those observed in placentas prior to the coronavirus pandemic. Full article

The development of effective anticoagulants remains a critical need in modern medicine, particularly for preventing and treating thromboembolic disorders, such as arterial thrombosis and deep vein thrombosis (DVT), as well as complications like ischemic stroke. This study identifies a cysteine-knotted peptide GC38 (sequence: GCSGKGARCAPSKCCSGLSCGRHGGNMYKSCEWNWKTG) derived from the venom gland transcriptome of the Macrothele sp. spider, which exerts thrombus-inhibitory effects by potentiating activated protein C (APC) activity. In vitro assays reveal that GC38 enhances APC activity, prolongs plasma clotting time, and shows no significant cytotoxicity or hemolytic activity. Mechanistically, GC38 interacts allosterically with APC; biolayer interferometry (BLI) confirms this direct interaction, with a dissociation constant K_D of 6.16 μM. Additionally, three in vivo thrombosis models (FeCl₃-induced arterial occlusion, stasis-induced DVT, and cortical photothrombotic stroke) consistently demonstrated that GC38 was effective in alleviating thrombus formation, with tail-bleeding assays confirming its low hemorrhagic risk. Collectively, our findings position GC38 as a pioneering spider venom-derived lead molecule that addresses dual arterial and venous antithrombotic actions. This opens new avenues for developing spider venom-derived peptides as therapeutic agents targeting intravascular coagulation in arteries and veins. Full article

Proteins containing the SQS-PSY domain, which include squalene synthetase (SQS), phytoene synthetase (PSY), and NDUFAF6, are functionally important and widely distributed in plants and animals. However, they have not been previously reported in nematodes. In this study, we identified a gene (Minc31999) encoding an SQS-PSY domain-containing protein in the root-knot nematode Meloidogyne incognita. In silico comparison and enzymatic assays of the recombinant protein indicated that this nematode protein is a putative NDUFAF6 homolog. Phylogenetic analysis revealed that this protein is evolutionarily conserved within the Nematoda phylum. RT-qPCR analysis showed that Minc31999 is highly expressed during the early infection stage of M. incognita. Targeting the nematode gene Minc31999 via host-induced gene silencing (HIGS) significantly hindered nematode development and virulence. In contrast, heterologous expression of Minc31999 in Arabidopsis thaliana disrupted normal plant development and increased host susceptibility to nematode infection. Transcriptomic profiling (RNA-seq) of these transgenic plants prior to infections showed a widespread differential expression of genes across multiple metabolic pathways. We propose that this nematode SQS-PSY domain-containing protein may function as an effector that rewires host secondary metabolism to establish a parasitic relationship. Our study elucidates a novel strategy in nematode–plant interactions and advances our understanding of the functional evolution of SQS-PSY domain-containing proteins. Full article

Knots are ubiquitous in polymers and biological macromolecules such as DNA and proteins, yet their behavior and functionality are still not sufficiently explored. Here we investigate the impact of Poiseuille flow on simple knots in flexible polymers placed in a quasi-rectangular micro-channel by systematically varying the flow strength for different chain lengths. Hydrodynamic interactions are accounted for by means of Multi-Particle Collision Dynamics (MPCD). We find that initially loosely localized knots in polymer coils typically tighten under shear to several segments beyond a certain body force threshold. At higher shear rates, intermittent transition from chain stretching to tumbling is observed which correlates with strong fluctuations in the knot size. Somewhat unexpectedly, our results indicate that the influence of channel width on tightening steadily increases with growing width even at equal mean shear rate $\overline{\dot{\gamma }}$. Full article

Light-harvesting chlorophyll a/b-binding (Lhc) proteins are integral membrane proteins that bind to pigment molecules, playing a critical role in photosynthetic processes, including light energy harvesting and transfer. To investigate the role of the Lhc gene family in cucumber (Cucumis sativus L), genome-wide identification of CsLhc gene family members and analysis of their regulatory networks were carried out using bioinformation and molecular biology research methods at Anhui Science and Technology University. The results indicated that the Lhc family consisted of 21 members, being categorized into five subfamilies: Lhca, Lhcb, CP24, CP26, and CP29. The gene structure and motifs within each subfamily are generally conserved. CsLhcs are distributed on seven chromosomes, including one pair of tandem duplicates and two pairs of segmental duplicates. Six CsLhcs exhibit eight linear relationships with seven AtLhcs, and one CsLhc shows a syntenic relationship with one OsLhc. Analysis of the cis-acting elements in CsLhc promoters revealed their potential involvement in stress responses. Transcriptome data indicated that CsLhcs are minimally expressed in male flowers and roots, but highly expressed in other organs. Analysis of stress response processes revealed that all Lhc genes participate in at least one stress response. Five Lhc genes were confirmed to appear to have expression change using qPCR analysis under high temperature and salt stress. Particularly, under downy mildew, root-knot nematode stresses, and blight stress, up-regulated Lhc genes were the most abundant ones, indicating that the Lhc family acts as a significant role in the growth and development of cucumber. These results provide valuable insights for further understanding the characteristics of the CsLhc family and analyzing the function of the Lhc family in cucumber resistance to biotic/abiotic stresses and in molecular breeding. Full article

Metronidazole is the preferred drug for treating amoebiasis caused by Entamoeba histolytica. Its antiamoebic activity is primarily attributed to activation by various reductases. This study reports an alternative activation pathway in E. histolytica mediated by the decarboxylating malic enzyme. Functional characterization of this NADPH-dependent enzyme reveals that it is secreted into the extracellular milieu and may play a role in E. histolytica adhesion to human enteric cells. Structural analysis of the E. histolytica malic enzyme (EhME) demonstrates that the protein forms a strict dimer, with the protomers interlocked by a unique knot structure formed by two polypeptide chains. This distinctive structural feature closely aligns EhME with its prokaryotic counterparts. In conclusion, our findings reveal that E. histolytica harbors a deeply entangled dimeric malic enzyme that contributes to metronidazole susceptibility, sharing structural similarities with bacterial malic enzymes. Full article

The interleukin (IL)-17 family encompasses six structurally related pro-inflammatory cystine knot proteins, designated as IL-17A to IL-17F. Over the last decades, evidence has pointed to its role as a critical player in the development of inflammatory diseases such as psoriasis (PsO), axial spondyloarthritis (axSpA), and psoriatic arthritis (PsA). More specifically, IL-17A and IL-17F are overexpressed in the skin and synovial tissues of patients with these diseases, and recent studies suggest their involvement in promoting inflammation and tissue damage in axSpA and PsA. Bimekizumab is a monoclonal antibody targeting both IL-17A and IL-17F, playing an important role in the treatment of these diseases. This review details the implications of bimekizumab in the therapeutic armamentarium of axSpA and PsA. Full article

Triple-negative breast cancer (TNBC) is a type of breast cancer characterized by high molecular heterogeneity. Owing to the lack of effective therapeutic strategies, patients with TNBC have a poor prognosis. Prunella vulgaris L. has the effects of reducing swelling, dissolving knots and treating breast carbuncles and mammary rocks. Modern pharmacological studies have reported that it can effectively inhibit the growth of breast cancer. The main active antitumor components of Prunella vulgaris are triterpenoids (PVT); however, the role and potential mechanism of PVT in TNBC remain unexplored. Our study aimed to further explore the inhibitory effects of PVT on TNBC and the associated mechanism. The results showed that 19 compounds associated with PVT were identified, 9 of which were triterpenoids. The percentages of ursolic acid and oleanolic acid in PVT were 34.51% and 11.32%, respectively. Triterpenes of Prunella vulgaris significantly inhibited the proliferation, migration and invasion of MDA-MB-231 cells and promoted their apoptosis in a concentration-dependent manner. PVT could also effectively downregulate the mRNA and protein expression levels of Ptp1b, Pi3k, Akt and mtor and upregulate the mRNA and protein expression levels of Il-24 in MDA-MB-231 cells. In mice with tumors of TNBC, PVT significantly reduced tumor growth and the expression levels of PTP1B, CXCL12, CXCR4, PI3K, AKT, mTOR and other proteins in TNBC tumor tissue and upregulated the expression of IL-24. This study showed that PVT played an anti-TNBC role by regulating the PTP1B/PI3K/AKT/mTOR signaling pathway and the IL-24/CXCL12/CXCR4 signaling axis. Full article

Meloidogyne causes a devastating disease known as root-knot that affects tomatoes and other cash crops worldwide. Conversely, Paraburkholderia tropica has proven beneficial in mitigating the effects of various pathogens in plants. We aimed to unravel the molecular events that underlie the beneficial effects of the bacterium and the detrimental impacts of the nematode when inoculated separately or together in tomato plants. The transcriptional responses induced by P. tropica (TB group (tomato-bacteria group)), Meloidogyne spp. (TN group (tomato-nematode group)) or by the two agents (TBN group (tomato-bacteria-nematode group)) in tomato were assessed by RNA-seq. We implemented a transcript discovery pipeline which allowed the identification of 2283 putative novel transcripts. Differential expression analysis revealed that upregulated transcripts were much more numerous than downregulated ones. At the gene ontology level, the most activated term was ‘hydrolase activity acting on ester bonds’ in all groups. In addition, when both microbes were inoculated together, ‘hydrolase activity acting on O-glycosyl compounds’ was activated. This finding suggests defense responses related to lipid and carbohydrate metabolism, membrane remodeling and signal transduction. Notably, defense genes, transcription factors and protein kinases stood out. Differentially expressed transcripts suggest the activation of a multifaceted plant defense response against the nematode occurred, which was exacerbated by pre-inoculation of P. tropica. Full article

This study investigates the nutritional composition and bioactive properties of Palmaria palmata (dulse), Ascophyllum nodosum (knotted wrack), and Chondrus crispus (Irish moss). Understanding the nutritional values of these seaweeds is very important due to their potential health benefits, especially their antioxidant properties and cytotoxic activities, which point to their ability to inhibit cancer cell proliferation. Comprehensive analyses were conducted to assess protein content, amino acid composition, mineral profile, fatty acids, polyphenols, total carotenoids, antioxidant activity, and cytotoxicity against cervical (HeLa), and colon (HCT-116) cell lines. P. palmata exhibited the highest protein content, while C. crispus was richest in calcium, iron, manganese, and zinc. Amino acid analysis revealed C. crispus as being particularly high in essential and non-essential amino acids, including alanine, glutamic acid, and glycine. A. nodosum and C. crispus were rich in polyunsaturated fatty acids (PUFAs), notably eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). A. nodosum showed the highest total carotenoid content. Polyphenol analysis highlighted the presence of compounds such as p-coumaric acid, gallic acid, and p-hydroxybenzoic acid across the species. Both the ethanolic and hexane A. nodosum extracts demonstrated the strongest antioxidant potential in DPPH^• and ABTS⁺ assays. The cytotoxicity evaluation revealed high anticancer activity of A. nodosum and C. crispus hexane extract against HeLa and HCT-116, though it employed cell cycle arrest and apoptosis. A. nodosum hexane extract exhibited moderate selective anticancer activity against HCT-116. These findings underscore the nutritional diversity and potential health benefits of these macroalgae (seaweed) species, suggesting their suitability as functional foods or supplements, offering diverse nutritional and therapeutic benefits. Full article