Current Issues in Molecular Biology最新文献

Hypermobile Ehlers-Danlos Syndrome (hEDS) is a hereditary connective tissue disorder characterized by joint hypermobility, skin hyperextensibility, and systemic manifestations such as chronic fatigue, gastrointestinal dysfunction, and neurological symptoms. Unlike other EDS subtypes with known genetic mutations, hEDS lacks definitive markers, suggesting a multifactorial etiology involving both mitochondrial dysfunction and non-mitochondrial pathways. This scoping review, conducted in accordance with the PRISMA-ScR guidelines, highlights mitochondrial dysfunction as a potential unifying mechanism in hEDS pathophysiology. Impaired oxidative phosphorylation (OXPHOS), elevated reactive oxygen species (ROS) levels, and calcium dysregulation disrupt cellular energetics and extracellular matrix (ECM) homeostasis, contributing to the hallmark features of hEDS. We reviewed candidate genes associated with ECM remodeling, signaling pathways, and immune regulation. Protein-protein interaction (PPI) network analyses revealed interconnected pathways linking mitochondrial dysfunction with these candidate genes. Comparative insights from Fabry disease and fragile X premutation carriers underscore shared mechanisms such as RNA toxicity, matrix metalloproteinases (MMP) activation, and ECM degradation. These findings may suggest that mitochondrial dysfunction amplifies systemic manifestations through its interplay with non-mitochondrial molecular pathways. By integrating these perspectives, this review provides a potential framework for understanding hEDS pathogenesis while highlighting latent avenues for future research into its molecular basis. Understanding the potential role of mitochondrial dysfunction in hEDS not only sheds light on its complex molecular etiology but also opens new paths for targeted interventions.

Cellular nucleosomes-the structural and functional units of chromatin-are inherently present in cells. During cellular damage or cell death, nucleosomes are released into circulation, either actively or passively. Once released, nucleosomes can become immunogenic entities through various mechanisms. The nucleosomal proteins in nucleosomes, called histones, play a pivotal role in inducing immunogenicity. However, intact nucleosomes are more immunogenic than the histones alone, as nucleosomal double-stranded deoxyribonucleic acid (dsDNA) enhances its immunogenic potential. Our recent study has shown that circulating histones are predominantly nucleosomal histones rather than free histones. Consequently, circulating histones primarily function as integral parts of circulating nucleosomes rather than acting independently. Circulating nucleosomes and their associated histones are implicated in the pathogenesis of a wide array of diseases. Notably, they are critical in the pathogenesis of lung injury and sepsis. These diseases have high morbidity and mortality rates and lack early diagnostic biomarkers. Further investigation is required to fully elucidate the role of circulating nucleosomes and their associated histones in disease processes. This review aims to discuss the current understanding of circulating nucleosomes and histones in the pathogenesis of lung injury and sepsis, with a focus on the underlying mechanisms.

Cellular senescence plays a crucial role in skin aging, with senescent dermal fibroblasts contributing to reduced skin elasticity and increased inflammation. This study investigated the potential of Ganoderma lucidum (Reishi) ethanol extract to modulate the senescent phenotype of human dermal fibroblasts. Reishi powder of two different vendors was used. The extract was produced by extracting the Reishi powder for at least three weeks in 40% ethanol at room temperature. Etoposide-induced senescent fibroblasts were treated with Reishi extracts from two commercial sources for 14 days. Gene expression analysis was performed using qPCR to assess senescence makers, antioxidant defense, and extracellular matrix remodeling. Results showed that Reishi extracts significantly upregulated antioxidant and cytoprotective genes, including Heme oxygenase 1 (HO-1), γ-Glutamylcysteine synthetase (γGCS-L), and NAD(P)H dehydrogenase [quinone] 1 (NQO1), compared to untreated controls. Importantly, Reishi treatment suppressed the expression of p16^INK4a, a key marker of cellular senescence, while transiently upregulating p21^Cip1. The extracts also demonstrated potential senolytic properties, reducing the percentage of senescent cells as measured by senescence-associated β-galactosidase staining. However, Reishi treatment did not mitigate the upregulation of MMP1 and IL-8 in one Reishi treatment group, indicating differences in the preparations of different vendors. These findings suggest that Ganoderma lucidum extract may help alleviate some aspects of cellular senescence in dermal fibroblasts, primarily through enhanced antioxidant defense and cytoprotection, potentially offering a novel approach to combat skin aging.

To identify stable reference genes for qRT-PCR analysis across different developmental stages and color variations of tender leaves in Litsea coreana, seven candidate reference genes were selected based on existing transcriptome data. qRT-PCR was performed on tender leaves of L. coreana at various stages and under different color conditions. The stability of these genes was evaluated using GeNorm (version 2003), NormFinder (version 0953), BestKeeper (version 2003), and ReFinder software (version 2004). The most stable genes were selected, and the stability of the chosen reference genes was validated. RPL and ACT were the most stable genes across different leaf developmental stages, while ACT and EF1-α showed the highest stability across different leaf colors. Overall, ACT and EF1-α were the most stable reference genes for both developmental stages and color variations. ACT and EF1-α can be used as reliable reference genes for gene expression studies in the color change process of L. coreana tender leaves. This will provide a foundation for further research into the molecular mechanisms of leaf color changes and the development of color regulation genes in L. coreana.

In a scenario characterized by continuous improvement in outcomes, Philadelphia chromosome-positive (Ph+) ALL, once considered a biologically defined subtype with one of the poorest prognoses, now includes patients achieving long-term survival even without allogeneic stem cell transplantation. First-line therapy is increasingly adopting a chemo-free approach, combining tyrosine kinase inhibitors (TKIs) with immunotherapy-specifically blinatumomab-which has resulted in high rates of complete molecular responses and improved survival outcomes. Within this paradigm shift, the allocation to transplantation is becoming increasingly selective and genomically oriented, focusing on patients with particularly unfavorable prognostic and predictive factors. For patients undergoing transplantation, maintenance therapy with TKIs has emerged as one of the most important strategies to reduce the risk of relapse. However, there remains considerable uncertainty regarding which patients benefit most from this approach, the optimal TKI agents, dosing strategies, and the duration of maintenance therapy. In this review, we aim to consolidate the available evidence on this topic, analyzing it in the context of the most recent clinical experiences.

Circulating small extracellular vesicles (sEVs) are emerging as potential biomarkers for glioblastoma progression. This study aimed to compare the levels of matrix metalloproteinases (MMP2 and MMP9), terminal complement complex (C5b-9), and VEGF-A in circulating sEVs in glioblastoma patients (GBMPs) with and without tumor recurrence. Using differential ultracentrifugation, sEVs were isolated from blood samples of GBMPs with no tumor recurrence for over one year (n = 6) and after first relapse (n = 14). The vesicles were characterized and quantified using flow cytometry. In both groups, C5b-9 was predominantly detected on tumor-specific circulating sEVs (glial fibrillary acidic protein (GFAP)-positive sEVs) with high VEGF-A expression, while C5b-9 was significantly less frequent on sEVs with low VEGF-A expression (p < 0.05). GFAP+VEGF+dimMMP2-C5b-9+ vesicles were rarely detected in GBMPs without relapse, suggesting their potential utility as biomarkers for a favorable relapse-free prognosis. In recurrent GBMPs, a positive correlation was observed between GFAP+VEGF+bright MMP2+C5b-9+ sEVs and MGMT gene promoter methylation levels (r = 0.543, p < 0.05). Additionally, a trend toward a negative correlation was found between GFAP+VEGF+bright MMP2+C5b-9- sEVs and mutant p53 expression in primary tumor tissue (r = -0.44, p = 0.114). These findings suggest that sEV profiles may serve as valuable prognostic markers for glioblastoma recurrence and treatment responses.

Colorectal cancer (CRC) is a common cancer globally, and chemotherapy often causes severe complications, necessitating effective drugs with minimal side effects. As Areca catechu L. extract (ACE) is a Traditional Chinese Medicine that contains numerous active compounds with anticancer effects, in this study, the Cell Counting Kit-8 (CCK-8) assay was used to determine ACE's effect on CRC cell lines, revealing that it significantly inhibits CoLo320DM and HCT116 cells. In vivo experiments with NU-Foxn1nu mice indicated that ACE inhibits tumor growth, while a flow cytometry assay revealed that higher ACE concentrations increased cell apoptosis and ROS levels. Next-generation sequencing (NGS) showed that ACE increases the fold changes in apoptosis, DNA damage, and autophagy-related genes while inhibiting the fold changes in cell proliferation and Wnt signaling pathway genes. We conducted Western blotting to confirm these findings. Overall, ACE demonstrates potential as a drug candidate by promoting apoptosis and autophagy, and significantly reducing cell viability and tumor growth, thus offering a new approach for effective colorectal cancer treatment with minimal side effects.

MicroRNAs play crucial roles in regulating inflammatory responses and disease progression. Since its identification on chromosome 17q11.2 in 2005, miR-451 has emerged as a key regulator of multiple physiological and pathological processes. While its role in cancer has been extensively documented, accumulating evidence reveals miR-451's broader significance in inflammatory conditions through the regulation of NF-κB, AMPK, and PI3K signaling pathways. This comprehensive review systematically analyzes miR-451's multifaceted functions in inflammatory diseases, with particular focus on ischemia-reperfusion injury, arthritis, and acute organ injuries. We present compelling evidence for miR-451's potential as a diagnostic biomarker, demonstrating its distinctive expression patterns across various biological specimens and disease states. Furthermore, we elucidate how miR-451 modulates inflammatory responses through the regulation of immune cell populations, including microglia activation, macrophage polarization, and neutrophil chemotaxis. By integrating current evidence and bioinformatic analyses, we establish a theoretical framework linking miR-451's molecular mechanisms to its therapeutic applications. This review not only synthesizes the current understanding of miR-451 in inflammatory diseases but also provides critical insights for developing novel diagnostic tools and therapeutic strategies.

Over the past three decades, vagus nerve stimulation (VNS) has emerged as a promising rehabilitation therapy for a diverse range of conditions, demonstrating substantial clinical potential. This review summarizes the in vivo biological mechanisms activated by VNS and their corresponding clinical applications. Furthermore, it outlines the selection of parameters and equipment for VNS implementation. VNS exhibits anti-inflammatory effects, modulates neurotransmitter release, enhances neural plasticity, inhibits apoptosis and autophagy, maintains blood-brain barrier integrity, and promotes angiogenesis. Clinically, VNS has been utilized in the treatment of epilepsy, depression, headache, stroke, and obesity. Its potential applications extend to anti-inflammatory treatment and the management of cardiovascular and cerebrovascular diseases and various brain disorders. However, further experiments are required to definitively establish the efficacy of VNS's various mechanisms. Additionally, there is a need to explore and identify optimal rehabilitation treatment parameters for different diseases.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that may progress to colorectal cancer (CRC), presenting significant challenges to global health. With shifts in lifestyle, the incidence of both conditions continues to rise, underscoring the urgent need for effective treatments. While traditional therapies can be effective, their high recurrence rates and associated adverse reactions limit their broader application. Luteolin, a flavonoid derived from natural plants, has emerged as a promising focus in both IBD and CRC research due to its multi-target therapeutic potential. This article reviews the molecular mechanisms and signaling pathways through which luteolin regulates immune cell differentiation, mitigates inflammation and oxidative stress, modulates gut microbiota, and restores intestinal mucosal barrier function in IBD. In the context of CRC, luteolin demonstrates significant anti-tumor effects by inhibiting cancer cell proliferation, inducing apoptosis, and suppressing cell migration and invasion. Notably, luteolin has demonstrated significant improvements in IBD symptoms by influencing the differentiation of T cell subsets, decreasing the expression of inflammatory mediators, activating antioxidant pathways, and enhancing the structure of gut microbiota. Furthermore, advancements in formulation technology, such as the use of polymer micelles and responsive nanoparticles, have greatly improved the bioavailability and efficacy of luteolin. However, further investigation is needed to address the bioavailability and potential toxicity of luteolin, particularly in the critical transition from IBD to CRC. This article emphasizes the potential of luteolin in the treatment of IBD and CRC and anticipates its promising prospects for future clinical applications as a natural therapeutic agent.