Current Issues in Molecular Biology最新文献

Absence epilepsy (AE) is a common pediatric epilepsy syndrome marked by brief lapses in consciousness and characteristic 2.5-4 Hz spike-and-wave discharges on EEG. Although its clinical and electrophysiological features are well established, the molecular mechanisms underlying AE remain incompletely understood. Proteomic approaches offer a powerful means to explore these mechanisms; however, their application in AE remains limited and methodologically heterogeneous, which complicates data integration. In this review, proteomic methodologies applied in rodent models of absence epilepsy are critically examined, including genetic rat models such as Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and Wistar Albino Glaxo rats from Rijswijk (WAG/Rij), monogenic mutant mouse models, and pharmacologically induced models. The technical workflow is described particularly, from tissue sampling and protein preparation (including gel-based and gel-free methods) to mass spectrometric analysis using data-dependent and data-independent acquisition strategies. Emerging technologies such as spatial proteomics, Trapped Ion Mobility Spectrometry coupled with Parallel Accumulation-Serial Fragmentation (TIMS-PASEF), and the integration of artificial intelligence are also evaluated in relation to their potential to address current technical limitations. Beyond synthesizing convergent molecular pathways including synaptic dysfunction, altered energy metabolism, and neuroinflammation, the review examines how methodological choices-such as model selection, brain region dissection, sample preparation protocols, and analytical platforms-contribute to experimental outcomes and data interpretation. By integrating current evidence with a focus on methodological aspects, this review provides a framework for designing more robust, reproducible, and clinically relevant proteomic studies in absence epilepsy.

In this study, the structure of Walnut green husk polysaccharides (WGHP) and their effects on immune checkpoint inhibitor induced colitis (ICIIC) and intestinal microbiota in mice were studied. The results showed that WGHP was composed of mannose (Man) 0.56%, rhamnose (Rha) 6.81%, galacturonic acid (GalA) 53.52%, glucose (Glc) 8.93%, galactose (Gal) 13.94%, arabinose (Ara) 15.88% and fucose (Fuc) 0.35%. The results of animal experiments showed that the intake of WGHP could not only effectively improve the phenotype of ICIIC in mice, but also significantly regulate the composition of intestinal flora and the content of short-chain fatty acids in mice, such as regulating the ratio of Firmicutes/Bacterotoides, Lachnospiraceae NK4A136 group, Lactobacillus, and increasing the content of butyric acid, acetic acid, and isobutyric acid to restore intestinal homeostasis. In addition, WGHP improves inflammation in mouse ICIIC by inhibiting the secretion of pro-inflammatory cytokines TNF-α and IL-1β, thereby activating the GPR43/PD-1/PD-L1 signaling pathway. Therefore, WGHP can be used as a functional polysaccharide for the prevention of ICIIC.

Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are important components of bone marrow, possessing multipotent differentiation potential and the ability to support hematopoiesis. Exposure to ionizing radiation (IR) induces cellular damage in BM-MSCs, such as DNA lesions and mitochondrial dysfunction. Despite their relative radioresistance, most surviving BM-MSCs enter senescence post-irradiation. This senescent state disrupts the bone marrow niche, impairs stem cell proliferation and differentiation, and contributes to acute radiation syndrome (ARS) and myelosuppression. To clarify the impact of IR on BM-MSCs, this review systematically summarizes the general mechanisms of radiation-induced cellular senescence, examines the effects of different radiation types (e.g., gamma rays, X-rays, and heavy-ion radiation) and doses on BM-MSCs senescence, and outlines senotherapeutic strategies targeting BM-MSCs senescence. The analysis indicates that the senescence of BM-MSCs caused by IR is type- and dose-dependent. The review identifies key factors in IR-induced BM-MSCs senescence to guide targeted interventions, highlighting the need for future studies to elucidate the underlying mechanisms of IR-induced BM-MSCs senescence.

Peptide nucleic acids (PNAs) are versatile molecules with promising diagnostic and therapeutic applications, including gene expression regulation and miRNA targeting. However, their moderate biological efficacy limits their therapeutic application. This can be addressed by leveraging a key advantage of PNAs over other nucleic acids-the ease of modification, which enhances their functional properties. Notably, γ-modified PNAs have improved binding affinity and cellular uptake properties, underscoring the potential of backbone engineering. In this study, we introduced a novel γ-amino carboxylic acid modification into PNAs targeting miR-221-3p, a key miRNA implicated in various pathological processes. The binding affinity of the modified PNAs to their targets and their ability to inhibit miR-221-3p expression were considerably higher than those of unmodified PNAs in Lung cancer cell lines, leading to effective regulation of downstream gene and protein expression. These findings underscore the potential of γ-modified PNAs as a platform for developing miRNA-targeted therapeutics.

We thank Lago and Bolognani [...].

Bacillus amyloliquefaciens is an important agricultural microbial resource. This study focuses on the whole genome analysis and functional characterization of B. amyloliquefaciens SH-53, isolated from the Wuliang Mountain National Nature Reserve in Dali, Yunnan. The genomic feature analysis revealed that the genome of SH-53 contains 27 ribosomal RNA operons, 4078 protein-coding genes, and 250 prophage-related genes. Additionally, 12 biosynthetic gene clusters (BGCs) for secondary metabolites were predicted, of which 7 are novel gene clusters with unknown functions, showing significant differences compared to the known BGCs of conventional biocontrol strains. Functional potential analysis indicates that SH-53 possesses potential antagonistic activity against plant pathogenic bacteria and can colonize the plant rhizosphere through various mechanisms to exert growth-promoting effects. It is capable of synthesizing multiple antibacterial secondary metabolites, indole-3-acetic acid (IAA), iron carriers, secreting amylase, and efficiently utilizing sulfur sources. The genome also harbors a complete core gene network related to the induced systemic resistance (ISR) and supporting genes that maintain secondary metabolism homeostasis. In conclusion, B. amyloliquefaciens SH-53 exhibits rich biocontrol-related characteristics and unique secondary metabolic potential, indicating promising prospects for its development as an excellent biocontrol agent.

Refractory infections caused by multidrug-resistant bacteria have emerged as a substantial threat to public health, prompting renewed interest in phage therapy. Bacteria and phages are ubiquitous in diverse environments, engaging in continuous interaction and co-evolution. In response to phage infection, bacteria have developed an array of defense mechanisms. Current studies on bacteria-phage interactions predominantly focus on laboratory settings using artificial media, whereas the final goal of phage therapy-to combat antibiotic-resistant bacteria-lies in its clinical application. This review describes bacterial defense strategies against phage infection in the context of laboratory-based artificial media, animal experiments and clinical cases, aiming to deepen the understanding of bacteria-phage interactions and promote the advancement of effective phage therapy for clinical applications.

The importance of protein-based materials in agricultural pest control has received increasing attention in recent years. Herein, Plutella xylostella brush-border membrane vesicles (BBMVs) were used as a target to screen for human domain antibodies with insecticidal activity. Three rounds of panning of the phage display library yielded the domain antibody C4D, which competed with the Cry1Ac toxin to bind to P. xylostella BBMVs. Against P. xylostella larvae, the recombinant soluble C4D protein showed an LC₅₀ of 1.57 μg/cm² (95% fiducial limits: 0.83-2.54). Using pull-down assays and liquid chromatography-tandem mass spectrometry, we identified the C4D binding partner in P. xylostella midgut BBMVs to be a cadherin-like protein. Bio-Layer Interferometry assay revealed that the dissociation constant between soluble C4D and P. xylostella cadherin-like protein was 2.99 × 10^-6 M. Thus, the present study explored strategies to generate insecticidal antibodies, and the human domain antibody C4D identified and characterized in this study can serve as a framework for generating novel insecticidal agents.

Soybean (Glycine max) is a globally important crop valued for its high seed oil and protein content. However, lodging remains a major abiotic constraint that causes substantial yield losses. Lodging resistance is primarily determined by stem strength and toughness, which are governed by stem anatomical organization, vascular tissue development, and the composition and architecture of secondary cell walls (SCWs). This review synthesizes current knowledge on anatomical, structural, and genetic factors that are implicated in stem mechanical performance in dicotyledonous plants, with particular emphasis on vascular cambium activity, xylem and phloem differentiation, and the biosynthesis of major SCW components, including cellulose, hemicellulose, and lignin. These processes collectively determine stem rigidity, flexibility, and resistance to mechanical stress. By integrating insights from model species, especially Arabidopsis thaliana, and non-soybean dicots, this review highlights conserved regulatory pathways controlling stem development and SCW formation that are directly relevant to soybean improvement. The synthesis provides a translational framework for understanding how conserved anatomical and genetic mechanisms can be leveraged to enhance soybean stem strength, toughness, and lodging resistance. Overall, this review provides a conceptual foundation for future functional studies and breeding strategies to improve soybean yield stability and adaptability across diverse agronomic conditions.

Oxidative and nitrosative stress are key contributors to the development and progression of chronic inflammatory disorders, cancer and neurodegenerative diseases (viz., Alzheimer's disease). Cholinergic dysfunction is a major hallmark of Alzheimer's disease and is closely associated with these processes. Red seaweeds are rich in bioactive compounds that have been increasingly investigated for their potential to modulate these processes. This review aims to examine the role of major red seaweed-derived metabolites in regulating redox imbalance, immunomodulatory capacity and acetylcholinesterase activity, with emphasis on in vitro studies. An analysis of peer-reviewed literature was conducted, focusing on chemical, biochemical and cell-based assays. Studies assessed antioxidant activity, anti-inflammatory and immunostimulatory effects, and acetylcholinesterase inhibition of isolated compounds/fractions of red seaweed using established methods, including radical scavenging assays, Griess-based nitrite assay and enzyme inhibition assays. Sulfated polysaccharides, oligosaccharides, mycosporine-like amino acids (MAAs), phycoerythrin, bromophenols, phlorotannin and terpenoid-derived metabolites demonstrated antioxidant capacity through radical scavenging, metal chelation and modulation of endogenous antioxidants. They also modulated inflammatory mediators, including nitric oxide and pro-inflammatory cytokines, and inhibited acetylcholinesterase (AChE) activity. In vitro evidence supports red seaweed-derived compounds as promising modulators of redox homeostasis, inflammation and cholinergic function, highlighting their relevance as functional food ingredients, while underscoring the need for in vivo and clinical validation.