Current Issues in Molecular Biology最新文献

Modern sequencing and high-throughput profiling technologies [...].

Acute lung injury (ALI) is a severe inflammatory condition with high mortality rates, necessitating the development of effective therapeutic agents. Polydeoxyribonucleotide (PDRN), a DNA-derived compound known for its tissue repair and anti-inflammatory properties, has gained attention as a potential therapeutic agent. However, the efficacy of PDRN derived from marine sources, particularly Porphyra sp. (laver), remains unexplored in respiratory inflammation. In this study, we investigated the protective effects of Porphyra sp.-derived PDRN (Ps-PDRN) against LPS-induced ALI in mice through two administration routes: intranasal (IN) and oral (PO). Ps-PDRN treatment significantly attenuated fever, pulmonary edema, and histopathological changes in LPS-challenged mice. Both IN and PO administration of Ps-PDRN markedly reduced proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and chemokines (MCP-1, RANTES, CXCL1, and MIP-2) in bronchoalveolar lavage fluid (BALF) and serum. Comparative analysis of the two administration routes revealed distinct efficacy profiles, with oral administration demonstrating superior chemokine inhibition, while intranasal delivery showed advantages in certain cytokine suppression. Histological examination revealed that Ps-PDRN preserved alveolar architecture and reduced inflammatory cell infiltration. Furthermore, in vitro studies using RAW 264.7 macrophages demonstrated that Ps-PDRN inhibited LPS-induced production of proinflammatory cytokines, such as TNF-α and IL-6, in a dose-dependent manner. These findings suggest that Ps-PDRN exerts potent anti-inflammatory effects against ALI through both local and systemic administration routes, highlighting its potential as a novel therapeutic agent for inflammatory lung diseases.

Occult hepatitis B infection (OBI) and mutated forms of the hepatitis B virus (HBV) represent diagnostic challenges, especially in individuals with atypical serological profiles. This study explores the molecular characteristics of HBV in HBsAg-negative women of childbearing age exhibiting atypical serological markers. We selected 100 HBsAg-negative sera from a cohort of 433 women aged 15-45 years. Additional HBV serological markers (anti-HBc, anti-HBs, HBeAg, anti-HBe) were assessed. Real-time PCR targeting the HBV S gene was performed on samples presenting atypical profiles. Socio-demographic and clinical correlates were also analyzed. Atypical serological profiles were identified in 23% of HBsAg-negative women, including combinations such as isolated anti-HBe positivity and anti-HBe with anti-HBc. Among these, none tested positive for HBV DNA by real-time PCR. Atypical profiles were more prevalent among women attending antenatal consultations and those aged under 25 years. The absence of detectable HBV DNA suggests either very low viral loads, resolved past infections, or serological artifacts due to mutated HBV strains. The high frequency of atypical serological patterns among HBsAg-negative women underscores the need to refine molecular diagnostic tools for detecting occult or mutated HBV. Further sequencing and genotypic characterization studies are warranted.

Soil salinity is a major constraint on global agricultural productivity. This study evaluated the efficacy of a cell-free extract from Trichoderma hamatum (designated BEYF) in enhancing salt stress tolerance in lettuce (Lactuca sativa). Lettuce plants under normal and salt-stressed conditions exposed to 200 mM NaCl were treated with either water or YF (the working solution of BEYF) at concentrations of 0.05, 0.10, and 0.25 mg/L. Compared to the control, YF application significantly improved plant growth under salt stress, as indicated by increased plant height, biomass, leaf area, and other agronomic traits. Physiologically, YF mitigated oxidative membrane damage, as indicated by reduced electrolyte leakage and malondialdehyde (MDA) content, while promoting the accumulation of the osmoprotectant proline. Histochemical staining further confirmed that YF effectively suppressed hydrogen peroxide (H₂O₂) accumulation and preserved cell viability under salt stress. At the molecular level, YF significantly up-regulated the expression of key stress-responsive genes, including those involved in abscisic acid biosynthesis (NCED1, NCED2), signaling (WRKY58), and proline synthesis (P5CSs). Collectively, our findings demonstrate that BEYF enhances lettuce salt tolerance through integrated physiological, cellular, and transcriptional adaptations, supporting its potential as a sustainable biostimulant for improving crop cultivation in saline soils.

Sorghum genotypes differentially shape their rhizosphere microbiomes to cope with salt stress; however, the modulatory role of biochar in this genotype-specific plant-microbe interplay remains unclear. In this study, we investigated how salt-sensitive (Henong 16, HN16) and salt-tolerant (Jizaonuo 1, JZN) sorghum genotypes leverage biochar to assemble distinct functional rhizosphere microbiomes under salt stress (5 g kg^-1 NaCl). Biochar application (20 g kg^-1) alleviated ionic stress by reducing soil electrical conductivity (EC decreased by 46% in HN16) and enhanced soil fertility through increased organic matter (SOM increased by 26% in JZN). 16S rRNA gene sequencing revealed that biochar selectively enriched genotype-specific, stress-resistant taxa. The salt-sensitive HN16 primarily recruited Sporosarcina (a genus reported to exhibit salt tolerance and nitrogen-fixing capabilities) and Intrasporangiaceae, thereby rapidly establishing a rhizosphere barrier. In contrast, the salt-tolerant JZN consistently enriched Salinimicrobium (an extreme halophile) and the family LWQ8, forming more complex and stable co-occurrence networks with a higher proportion of positive correlations (81%). Plant genotype was the primary determinant of core microbiome assembly: Bacillus and Arthrobacter dominated in HN16, whereas Sphingomonas and Streptomyces prevailed in JZN. Biochar reinforced this genotype-specific assembly by modulating soil pH and SOM, which were identified as key drivers of microbial community divergence. Importantly, these biochar-shaped microbial modules showed significant positive correlations with increased plant biomass. Our findings demonstrate that biochar enhances salt tolerance not merely by improving soil properties, but primarily by facilitating the deterministic assembly of genotype-specific, functional rhizosphere microbiomes. This mechanistic insight shifts the paradigm of biochar from a universal soil amendment to a precision tool for rhizosphere engineering, providing a genotype-aware foundation for enhancing salinity resilience in sustainable agriculture.

Jerusalem artichoke (JA) (Helianthus tuberosus), a perennial plant of the Asteraceae family, is well known for its high inulin content and diverse bioactive compounds, including flavonoids, phenolic acids, sesquiterpenes, and amino acids. Extracts derived from different parts of JA, such as tubers, leaves, and flowers, have demonstrated a wide range of biological activities, including antioxidant, anti-inflammatory, antihyperglycemic, antihypertensive, and antifungal effects. These properties highlight JA's potential in the prevention and management of chronic diseases such as diabetes, cardiovascular disorders, obesity, and colorectal cancer. Recent studies also suggest that JA benefits skin health through anti-aging and barrier-protective mechanisms and enhances immune function by modulating the intestinal microbiota. Owing to its multifunctional physiological activities, JA is being explored as a valuable raw material for food, nutraceutical, cosmetic, and pharmaceutical applications. However, most existing research has focused primarily on inulin, while comprehensive studies on other bioactive constituents and their clinical validation remain limited. This paper aims to provide a comprehensive overview of the bioactive compounds present in JA, elucidate their health-promoting functions, discuss their pharmacokinetics, and outline future perspectives on their potential as functional ingredients and biohealth materials.

The AP2/ERF superfamily is a key class of transcription factors involved in plant responses to various stresses. As an ancient species, the olive tree (Olea europaea L.) exhibits considerable stress tolerance and wide adaptability. In this study, we identified 348 AP2/ERF genes in the cultivated olive variety 'Arbequina' at the whole-genome level. According to protein sequence alignments and phylogenetic analyses via the Maximum Likelihood method, these genes were classified into four major families: AP2, ERF/DREB, RAV, and Soloist. The ERF/DREB family was further divided into DREB and ERF subfamilies, each encompassing six groups (A1-A6 and B1-B6), with the ERF subfamily being the largest. Members of each group exhibited relatively consistent gene structures and domain/motif compositions of their encoded proteins; however, the distribution of cis-elements and expression patterns varied. Each AP2/ERF gene contained 12 light-responsive, three MeJA-responsive, three ABA-responsive, two anaerobic induction, and one MYB binding site on average. With the threshold of p value < 0.5, control TPM > 0, and |log₂(fold change)| > 0, 50 candidate genes were simultaneously up-regulated (30) or down-regulated (20) under four stress treatments (acid-aluminum, cold, disease, and wound), among which nine showed potential protein-protein interactions. This study provides a comprehensive genomic characterization of the AP2/ERF family in olive and identifies key candidate stress-responsive genes, establishing a foundation for future functional studies on the molecular mechanisms of stress adaptation in the olive tree.

Objective: This study aimed to identify clinically relevant regulators of pancreatic ductal adenocarcinoma (PDAC), a disease characterized by stromal remodeling and immune suppression, and to define their links to malignant progression and microenvironmental reprogramming. Methods: We integrated multi-cohort bulk, single-cell, and spatial transcriptomic datasets and subsequently validated bulk differential expression and network analyses with machine learning-based prioritization in an independent combined cohort (TCGA-PAAD plus GSE62452). Single-cell mapping was used to assess cell-type specificity, positioning candidates along inferCNV- and pseudotime-defined malignant continua. In Visium sections, a DKK1-associated program score quantified intratumoral spatial heterogeneity and informed our analyses of ligand-receptor communication. Bulk immune deconvolution linked gene levels to immune infiltration patterns, and functional assays were used to test the impact of DKK1 knockdown on migration, proliferation, clonogenic growth, and apoptosis in PDAC cells. Results: Four reproducible tumor-associated genes-DKK1, COL10A1, SULF1, and SLC24A3-were prioritized and validated externally. DKK1 was predominantly expressed by epithelial tumor cells and tracked along a malignant progression continuum. Spatially, the DKK1 program localized to epithelial-dominant regions, revealed pronounced intratumoral heterogeneity, and highlighted epithelial-endothelial and endothelial-immune signaling in high-score areas. Immune deconvolution associated higher DKK1 expression with increased myeloid infiltration and reduced cytotoxic lymphocyte signatures. Functionally, DKK1 knockdown impaired migration, proliferation, and clonogenicity while increasing apoptosis. Conclusions: We demonstrate that DKK1 is an epithelial-derived regulator linked to malignant progression and tumor-stroma-immune remodeling, supporting its potential as a biomarker and therapeutic target in PDAC treatment, including rational combinations with stroma-modulating strategies and immunotherapy.

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Serrated adenocarcinoma (SAC) represents a molecularly heterogeneous subtype of colorectal carcinoma (CRC) linked to the serrated pathway. It is aimed to clarify the molecular mechanisms underlying SAC development. Digital slides from The Cancer Genome Atlas (TCGA) colorectal adenocarcinoma Firehose Legacy dataset (632 cases) were reviewed, and cases were classified as SAC, partial-SAC, or classical CRC. Genomic alterations, mRNA expression, and DNA hypermethylation were compared using cBioPortal. Enrichment analyses were performed via WebGestalt, and protein-protein interaction (PPI) networks with hub genes were identified using STRING and Cytoscape. Statistical significance was defined as p < 0.05 and q < 0.05. The results revealed that the groups showed significant differences in the expression of 327 genomic alterations, 20 mRNAs, and 21 methylated genes (p < 0.0001, q < 0.0001). Hub genes were PSMC1, FLT3LG, SNW1, H3C2, H1-2, H2BC14, H1-5, RPS16, SUPT5H, and MYOD1. The pathways associated with differently expressed genes were the following: cell structure and morphology (phagocytic vesicle, microvillus, endocytosis, and immobile cilium), protein kinase activity (particularly MAPK), and immunological mechanisms. The hub genes act as molecular bridges connecting the observed genomic and epigenetic variations, particularly driving chromatin-related regulation and MAPK signaling pathways. In particular, PSMC1, SNW1, H3C2, H1-2, and H2BC14 genes offer promising molecular targets for future therapeutic approaches in SACs.