Biology Direct最新文献

Background: Endometrial cancer (EC) presents significant clinical challenges due to its heterogeneity and complex pathophysiology. SAMHD1, known for its role as a deoxynucleotide triphosphate triphosphohydrolase, has been implicated in the progression of various cancers, including EC. This study focuses on elucidating the role of SAMHD1 in EC through its impact on TRIM27-mediated PTEN ubiquitination.

Results: Utilizing a combination of bioinformatics and cellular biology techniques, we investigated the interactions among SAMHD1, TRIM27, and PTEN. Our findings reveal that SAMHD1 modulates PTEN ubiquitination via TRIM27, impacting key pathways involved in EC pathogenesis. These interactions suggest a critical mechanism by which SAMHD1 could influence tumor behavior and progression in EC.

Conclusions: The results from this study underscore the potential of targeting the SAMHD1-TRIM27-PTEN axis as a therapeutic strategy in EC. By providing new insights into the molecular mechanisms underlying EC progression, our research supports the development of novel therapeutic approaches that could contribute to improve treatment strategies for patients with EC.

Background: Motile Sperm Domain-Containing Protein 1 (MOSPD1) has been implicated in breast cancer (BC) pathophysiology, but its exact role remains unclear. This study aimed to assess MOSPD1 expression levels in BC versus normal tissues and investigate its diagnostic potential.

Methods: MOSPD1 expression was analyzed in BC and normal tissues, with Receiver Operating Characteristic analysis for diagnostic evaluation. Validation was performed using immunohistochemistry. Functional studies included tumor growth assays, MOSPD1 suppression and overexpression experiments, and testing BC cell responses to anti-PD-L1 therapy.

Results: MOSPD1 expression was significantly higher in BC samples than normal tissues, correlating with poor clinical outcomes in BC patients. MOSPD1 suppression inhibited tumor growth, while overexpression accelerated it. Silencing MOSPD1 enhanced BC cell sensitivity to anti-PD-L1 therapy and decreased Th2 cell activity. In vivo experiments supported these findings, showing the impact of MOSPD1 on tumor growth and response to therapy.

Conclusions: Elevated MOSPD1 levels in BC suggest its potential as a biomarker for adverse outcomes. Targeting MOSPD1, particularly with anti-PD-L1 therapy, may effectively inhibit BC tumor growth and modulate immune responses. This study emphasizes the significance of MOSPD1 in BC pathophysiology and highlights its promise as a therapeutic target.

Plants have an amazing ability to adapt to their environment, and this extends beyond biochemical responses and includes developmental changes that help them better exploit resources and survive. The plasticity observed in individual plant morphology is associated with robust developmental pathways that are influenced by environmental factors. However, there is still much to learn about the mechanisms behind the formation of the root system. In Arabidopsis thaliana, the root system displays a hierarchical structure with primary and secondary roots. The process of lateral root (LR) organogenesis involves multiple steps, including LR pre-patterning, LR initiation, LR outgrowth, and LR emergence. The study of root developmental plasticity in Arabidopsis has led to significant progress in understanding the mechanisms governing lateral root formation. The importance of root system architecture lies in its ability to shape the distribution of roots in the soil, which affects the plant's ability to acquire nutrients and water. In Arabidopsis, lateral roots originate from pericycle cells adjacent to the xylem poles known as the xylem-pole-pericycle (XPP). The positioning of LRs along the primary root is underpinned by a repetitive pre-patterning mechanism that establishes primed sites for future lateral root formation. In a subset of primed cells, the memory of a transient priming stimulus leads to the formation of stable pre-branch sites and the establishment of founder cell identity. These founder cells undergo a series of highly organized periclinal and anticlinal cell divisions and expansion to form lateral root primordia. Subsequently, LRP emerges through three overlying cell layers of the primary root, giving rise to fully developed LRs. In addition to LRs Arabidopsis can also develop adventitious lateral roots from the primary root in response to specific stress signals such as wounding or environmental cues. Overall, this review creates an overview of the mechanisms governing root lateral root formation which can be a stepping stone to improved crop yields and a better understanding of plant adaptation to changing environments.

The immune response gene 1 (IRG1) and its metabolite itaconate are implicated in modulating inflammation and oxidative stress, with potential relevance to sepsis-induced myocardial dysfunction (SIMD). This study investigates their roles in SIMD using both in vivo and in vitro models. Mice were subjected to lipopolysaccharide (LPS)-induced sepsis, and cardiac function was assessed in IRG1 knockout (IRG1-/-) and wild-type mice. Exogenous 4-octyl itaconate (4-OI) supplementation was also examined for its protective effects. In vitro, bone marrow-derived macrophages and RAW264.7 cells were treated with 4-OI following Nuclear factor, erythroid 2 like 2 (NRF2)-small interfering RNA administration to elucidate the underlying mechanisms. Our results indicate that IRG1 deficiency exacerbates myocardial injury during sepsis, while 4-OI administration preserves cardiac function and reduces inflammation. Mechanistic insights reveal that 4-OI activates the NRF2/HO-1 pathway, promoting macrophage polarization and attenuating inflammation. These findings underscore the protective role of the IRG1/itaconate axis in SIMD and suggest a therapeutic potential for 4-OI in modulating macrophage responses.

Skin healing is a complex and dynamic physiological process that follows mechanical alteration of the skin barrier. Under normal conditions, this complex process can be divided into at least three continuous and overlapping phases: an inflammatory reaction, a proliferative phase that leads to tissue reconstruction and a phase of tissue remodeling. Macrophages critically contribute to the physiological cascade for tissue repair. In fact, as the inflammatory phase progresses, macrophage gene expression gradually shifts from pro-inflammatory M1-like to pro-resolutive M2-like characteristics, which is critical for entry into the repair phase. A dysregulation in this macrophage' shift phenotype leads to the persistence of the inflammatory phase. Mesenchymal stromal cells and specifically the MSC-derived from adipose tissue (ADSCs) are more and more use to treat inflammatory diseases and several studies have demonstrated that ADSCs promote the wound healing thanks to their neoangiogenic, immunomodulant and regenerative properties. In several studies, ADSCs and macrophages have been injected directly into the wound bed, but the delivery of exogenous cells directly to the wound raise the problem of cell engraftment and preservation of pro-resolutive phenotype and viability of the cells. Complementary approaches have therefore been explored, such as the use of biomaterials enriched with therapeutic cell to improve cell survival and function. This review will present a background of the current scaffold models, using adipose derived stromal-cells and macrophage as therapeutic cells for wound healing, through a discussion on the potential impact for future applications in skin regeneration. According to the PRISMA statement, we resumed data from investigations reporting the use ADSCs and bioscaffolds and data from macrophages behavior with functional biomaterials in wound healing models. In the era of tissue engineering, functional biomaterials, that can maintain cell delivery and cellular viability, have had a profound impact on the development of dressings for the treatment of chronic wounds. Promising results have been showed in pre-clinical reports using ADSCs- and macrophages-based scaffolds to accelerate and to improve the quality of the cutaneous healing.