Current Issues in Molecular Biology最新文献

Selecting high-quality varieties with disease resistance by artificial crossbreeding is the most fundamental way to address the damage caused by Calonectria spp. in eucalypt plantations. However, understanding the mechanism of disease-resistant heterosis occurrence in eucalypts is crucial for successful crossbreeding. Two eucalypt hybrids, the susceptible EC333 (H1522 × unknown) and the resistant EC338 (W1767 × P9060), were screened through infection with Calonectria isolates, a pathogen that causes eucalypt leaf blight. RNA-Seq was performed on the susceptible hybrid, the disease-resistant hybrid, and their parents. The gene differential expression analysis showed that there were 3912 differentially expressed genes between EC333 and EC338, with 1631 up-regulated and 2281 down-regulated genes. The expression trends of the differential gene sets in P9060 and EC338 were similar. However, the expression trend of W1767 was opposite that of EC338. The similarity of the expression and the advantage of stress resistance in E. pellita suggested that genes with significant differences in expression likely relate to disease resistance. A GSEA based on GO annotations revealed that the carbohydrate binding pathway genes were differentially expressed between EC338 and EC333. The gene pathways that were differentially expressed between EC338 and EC333 revealed by the GSEA based on KEGG annotations were the sesquiterpenoid and triterpenoid biosynthesis pathways. The alternative splicing analysis demonstrated that an AS event between EC338 and EC333 occurred in LOC104426602. According to our SNP analysis, EC338 had 626 more high-impact mutation loci than the male parent P9060 and 396 more than the female parent W1767; W1767 had 259 more mutation loci in the downstream region than EC338, while P9060 had 3107 fewer mutation loci in the downstream region than EC338. Additionally, EC338 had 9631 more mutation loci in the exon region than EC333. Modules were found via WGCNA that were strongly and oppositely correlated with EC338 and EC333, such as module MEsaddlebrown, likely associated with leaf blight resistance. The present study provides a detailed explanation of the genetic basis of eucalypt leaf blight resistance, providing the foundation for exploring genes related to this phenomenon.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising chemotherapeutic agent because of its selective apoptotic action on cancer cells. However, resistance to TRAIL-induced apoptosis remains a challenge in many cancers. The gintonin-enriched Panax ginseng extract fraction (GEF) has diverse pharmacological benefits. We explored the combined efficacy of GEF and TRAIL in inducing apoptosis in human renal cell carcinoma (RCC) cells. The effect of GEF treatment on the viability, clonogenic potential, wound healing, and TRAIL-induced apoptotic signaling of RCC cells was studied in vitro. Our investigation revealed that GEF pre-treatment sensitized RCC cells to TRAIL-induced apoptosis, as evidenced by DNA fragmentation and cell proliferation, colony formation, and migration inhibition. This sensitization was linked to the upregulation of death receptors 4 and 5 and alterations in apoptotic protein expression, notably, the decreased expression of the Mu-2-related death-inducing gene, a novel anti-apoptotic protein. Our findings underscore the necessity of caspase activation for GEF/TRAIL-induced apoptosis using the pan-caspase inhibitor Z-VAD-FMK. This study demonstrates that GEF sensitizes human RCC cells to TRAIL-induced apoptosis by upregulating DR4/5 and modulating apoptotic protein expression. These findings suggest a promising strategy for overcoming TRAIL resistance in cancer therapy and highlight the potential of GEF as a valuable adjunct to TRAIL-based treatments.

The present work shows that the exposure of mesothelial cells to simulated microgravity changes their cytoskeleton and adhesion proteins, leading to a cell switch from normal towards tumoral cells. Immunohistochemical and molecular data were obtained from both MeT-5A exposed to simulated microgravity and BR95 mesothelioma cell lines. Simulated microgravity was found to affect the expression of actin, vinculin, and connexin-43, altering their quantitative and spatial distribution pattern inside the cell. The analysis of the tumoral markers p27, CD44, Fibulin-3, and NANOG and the expression of genes related to cancer transformation such as NANOG, CDH-1, and Zeb-1 showed that the simulated microgravity environment led to expression patterns in MeT-5A cells similar to those observed in BR95 cells. The alteration in both quantitative expression and structural organization of the cytoskeleton and adhesion/communication proteins can thus be considered a pivotal mechanism involved in the cellular shift towards tumoral progression.

Recent studies revealed anomalous underscreening in concentrated electrolytes, and we suggest that the underscreened electrostatic forces between membrane proteins play a significant role in the process of self-assembly. In this work, we assumed that the underscreened electrostatic forces compete with the thermodynamic Casimir forces induced by concentration fluctuations in the lipid bilayer, and developed a simplified model for a binary mixture of oppositely charged membrane proteins with different preference to liquid-ordered and liquid-disordered domains in the membrane. In the model, like macromolecules interact with short-range Casimir attraction and long-range electrostatic repulsion, and the cross-interaction is of the opposite sign. We determine energetically favored patterns in a system in equilibrium with a bulk reservoir of the macromolecules. Different patterns consisting of clusters and stripes of the two components and of vacancies are energetically favorable for different values of the chemical potentials. Effects of thermal flutuations at low temperature are studied using Monte Carlo simulations in grand canonical and canonical ensembles. For fixed numbers of the macromolecules, a single two-component cluster with a regular pattern coexists with dispersed small one-component clusters, and the number of small clusters depends on the ratio of the numbers of the molecules of the two components. Our results show that the pattern formation is controlled by the shape of the interactions, the density of the proteins, and the proportion of the components.

Paper Mulberry (Broussonetia papyrifera) possesses medicinal, economic, and ecological significance and is extensively used for feed production, papermaking, and ecological restoration due to its ease of propagation, rapid growth rate, and strong stress resistance. The recent completion of the sequencing of the Paper Mulberry genome has prompted further research into the genetic breeding and molecular biology of this important species. A highly stable reference gene is essential to enhance the quantitative analysis of functional genes in Paper Mulberry; however, none has been identified. Accordingly, in this study, the leaves, stems, roots, petioles, young fruits, and mature fruits of Paper Mulberry plants were selected as experimental materials, and nine candidate reference genes, namely, α-TUB1, α-TUB2, β-TUB, H2A, ACT, DnaJ, UBQ, CDC2, and TIP41, were identified by RT-qPCR. Their stability was assessed using the geNorm, Normfinder, Delta Ct, BestKeeper, and RefFinder algorithms, identifying ACT and UBQ as showing the greatest stability. The expression of BpMYB090, which regulates the production of trichomes, was examined in the leaves of plants of the wild type (which have more trichomes) and mutant (which have fewer trichomes) at various developmental stages to validate the results of this study. As a result, their identification addresses a critical gap in the field of Paper Mulberry research, providing a solid foundation for future research that will concentrate on the characterization of pertinent functional genes in this economically valuable species.

Triple-negative breast cancer (TNBC) accounts for approximately 20% of all breast cancer cases and is characterized by a lack of estrogen, progesterone, and human epidermal growth factor 2 receptors. Current targeted medicines have been unsuccessful due to this absence of hormone receptors. This study explored the efficacy of Tulbaghia violacea, a South African medicinal plant, for the treatment of TNBC metastasis. Extracts from T. violacea leaves were prepared using water and methanol. However, only the water-soluble extract showed anti-cancer activity and the effects of this water-soluble extract on cell adhesion, invasion, and migration, and its antioxidant activity were assessed using MCF-10A and MDA-MB-231 cells. The T. violacea extract that was soluble in water effectively decreased the movement and penetration of MDA-MB-231 cells through the basement membrane in scratch and invasion tests, while enhancing their attachment to a substance resembling an extracellular matrix. The sample showed mild-to-low antioxidant activity in the antioxidant assy. Nuclear magnetic resonance spectroscopy revealed 61 chemical components in the water-soluble extract, including DDMP, 1,2,4-triazine-3,5(2H,4H)-dione, vanillin, schisandrin, taurolidine, and α-pinene, which are known to have anti-cancer properties. An in-depth examination of the transcriptome showed alterations in genes linked to angiogenesis, metastasis, and proliferation post-treatment, with reduced activity in growth receptor signaling, angiogenesis, and cancer-related pathways, such as the Wnt, Notch, and PI3K pathways. These results indicate that T. violacea may be a beneficial source of lead chemicals for the development of potential therapeutic medicines that target TNBC metastasis. Additional studies are required to identify the precise bioactive chemical components responsible for the observed anti-cancer effects.

To explore the mitogenome characteristics of Tetratomidae and the phylogenetic position of this family in Tenebrionoidea, the mitogenome of Penthe kochi Mařan, 1940 was sequenced, annotated, and analyzed. The P. kochi mitogenome is consistent with Tenebrionoidea species in gene length, genomic organization, codon usage, and secondary structures of transfer genes (tRNAs). Most protein-coding genes (PCGs) originate with a typical ATN start codon, except nad1 and nad3, which start with TTG. In total, 10 PCGs are terminated with complete stop codon TAA and TAG, while cox1, cox2, and nad 4 contain an incomplete stop codon T-. Among the 13 PCGs, nad2 (Pi = 0.282) has the most diverse nucleotide composition, and cox2 is the most conserved gene with the lowest value (Pi = 0.154). The Ka/Ks ratio of cox1 (0.076) and cox2 (0.124) has a lower value. All the tRNAs can be folded in a typical clover-leaf secondary structure, except trnS1, which lacked a dihydrouridine arm. And phylogenetic analyses were performed based on 13 PCGs using the Bayesian inference (BI) method. The results showed that the clade of Tenebrionoidea was well separated from the outgroups, and Tetratomidae and Mycetophagidae were not well resolved. Phylogenetic analyses with more mitogenome samplings are needed to resolve the phylogeny of Tenebrionoidea.

Aberrant expression of TRIM proteins has been correlated with poor prognosis and metastasis in many cancers, with many TRIM proteins acting as key oncogenic factors. TRIM proteins are actively involved in many cancer signaling pathways, such as p53, Akt, NF-κB, MAPK, TGFβ, JAK/STAT, AMPK and Wnt/β-catenin. Therefore, this review attempts to summarize how three of the most studied TRIMs in recent years (i.e., TRIM25, TRIM28 and TRIM59) are involved directly and indirectly in the crosstalk between the signaling pathways. A brief overview of the key signaling pathways involved and their general cross talking is discussed. In addition, the direct interacting protein partners of these TRIM proteins are also highlighted in this review to give a picture of the potential protein-protein interaction that can be targeted for future discovery and for the development of novel therapeutics against cancer. This includes some examples of protein partners which have been proposed to be master switches to various cancer signaling pathways.

The efficacy of treatment of head and neck squamous cell carcinoma (HNSCC) patients is still unsatisfactory, and there is an ongoing search for novel therapies. Locoregionally advanced HNSCC cases, which frequently require combined surgery and chemoradiotherapy, are especially difficult to treat. Natural compounds, like Magnolia-derived lignans-honokiol (HON) and magnolol (MAG)-can reduce cancer cell growth but retain a good safety profile and thus may show benefit as adjuvant therapeutics. The aim of this study was to evaluate the anti-cancer effects of HON and MAG in HNSCC cell lines and compare their effects between cisplatin-sensitive and cisplatin-tolerant cells. Cell viability was evaluated in FaDu and SCC-040 cells growing as monolayers and as spheroids. The effect of HON and MAG on the cell cycle, apoptosis, and gene expression was compared between wild-type FaDu cells and cisplatin persister FaDu cells. We observed that HON and MAG were more potent in reducing cell viability in cisplatin persister FaDu cells, although this effect was not directly followed by increased rates of apoptosis. Thus, HON's and MAG's capacity to affect cisplatin persister cells needs further studies. In general, we observed that HON exerted stronger cytotoxic effects than MAG in HNSCC cells, and the difference in their anti-cancer activity was especially pronounced in cells cultured in 3D.

The utilization of heavy-panicle hybrid rice exemplifies the successful integration of architectural enhancement and heterosis, which has been widely adopted in the southwest rice-producing area of China. Iterative improvement in disease resistance and grain quality of heavy-panicle hybrid rice varieties is crucial to promote their sustainable utilization. Here, we performed a molecular design breeding strategy to introgress beneficial alleles of broad-spectrum disease resistance and grain quality into a heavy-panicle hybrid backbone restorer line Shuhui 600 (R600). We successfully developed introgression lines through marker-assisted selection to pyramid major genes (Wx^b + ALK^A-GC + Pigm + Xa23) derived from three parents (Huanghuazhan, I135, I488), which significantly enhance grain quality and confer resistance to rice blast and bacterial blight (BB). The improved parental R600 line (iR600) exhibited superior grain quality and elevated disease resistance while maintaining the heavy-panicle architecture and high-yield capacity of R600. Moreover, the iR600 was crossed with male sterility line 608A to obtain a new heavy-panicle hybrid rice variety with excellent eating and cooking quality (ECQ) and high yield potential. This study presents an effective breeding strategy for rice breeders to expedite the improvement of grain quality and disease resistance in heavy-panicle hybrid rice.