Frontiers in Cell and Developmental Biology最新文献

Background/objectives: Prenatal alcohol exposure (PAE) has been recognized as a significant public health concern due to its consequential and long-lasting effects on the central nervous system (CNS) and the subsequent behavioral impairments in affected individuals. The current study aims to evaluate postnatal neurobehavioral disturbances, specifically mood state and potential morpho-functional changes, as well as brain oxidative stress in mice prenatally intoxicated with ethanol at the adult stage.

Methods: female mice with positive vaginal plugs were divided into three groups: Group 1 (ethanol intoxicated): received ethanol at a dose of 1 g/kg (i.p.) on gestational days 10 and 13 (two injections in total), along with pyrazole (100 mg/kg by i. p.) to inhibit ethanol metabolism and simulate chronic fetal exposure. The second group received pyrazole alone at the same dose (100 mg/kg i. p.). Group 3 (controls): received physiological saline solution (NaCl 0.9%) at the same volume as both ethanol and pyrazole. Offspring pups from the intoxicated dams were subjected, at the adult stage (from postnatal days P95 to P103), to a series of morphometric, biometric, neurobehavioral, and biochemical analyses.

Results: Our data show an obvious decrease in body weight and size, decreased food intake, and skeleton deformations. Additionally, PAE mice exacerbated anxiety-like and depressive-like behaviors as well as elevated brain oxidative stress.

Conclusion: The current data demonstrate the powerful neurotoxic effect of prenatal ethanol exposure on neuropsychological development as well as the associated morpho-functional changes.

The gut microbiota is increasingly recognized as a key determinant of cancer susceptibility, functioning as a dynamic interface between environmental exposures and host physiology. Dysbiosis disrupts immune homeostasis, epithelial integrity, and metabolic equilibrium, thereby fostering a microenvironment conducive to oncogenesis. Conversely, a balanced microbial ecosystem and its metabolites exert potent anti-tumor effects through immune modulation, maintenance of mucosal barrier function, and detoxification of carcinogens. This Review synthesizes emerging mechanistic insights into how commensal microbes and their metabolic products coordinate host defense pathways to suppress malignant transformation. We further discuss translational strategies-ranging from probiotics, prebiotics, and synbiotics to fecal microbiota transplantation and dietary interventions-that leverage microbiome modulation for cancer prevention. Despite compelling preclinical evidence, clinical translation remains constrained by inter-individual variability and incomplete mechanistic understanding. Integration of multi-omics analyses, gnotobiotic models, and precision microbial engineering offers a path toward microbiota-based interventions as a cornerstone of personalized cancer prevention and immunomodulation.

Several studies on the use of platelet concentrates show different results. For example, while many studies demonstrate significant benefits of using PCs in tissue regeneration, others report modest or no results, creating uncertainty about the actual clinical usefulness of these PCs. This confusion also arises from the different protocols used to prepare platelet concentrates, which became clearer after the classification of PCs based on the presence of leukocytes and the organization of fibrin. Currently, we have numerous devices available to obtain PCs with specific characteristics typical of each method, such as APG, PRF, PRGF, CGF, etc. On one hand, this wide range of options offered by companies creates confusion; on the other hand, it allows us to have systems that provide a uniform product for all operators by standardizing centrifugal force, the type of vial used, its inclination, and rotation time. The aim of this mini review is to provide an overview of the applications of Autologous Platelet Concentrates (APCs) and their clinical application.

Premature ovarian insufficiency (POI) is more than a fertility issue; it's a silent epidemic of accelerated systemic aging in young women, with current treatments failing to address its root cause. For too long, the relentless decline of ovarian function has been viewed as an inevitable mystery. But what if the ovary holds an internal "inflammatory clock," ticking away with each cellular insult and dictating the pace of its own decline? Here, we spotlight a surprising culprit: the cGAS-STING signaling pathway. Far beyond its day job in antiviral defense, this pathway emerges as a master integrator of ovarian aging. We reveal how stresses like DNA damage and mitochondrial dysfunction leak genetic material into the cell's interior, where cGAS-STING sounds a relentless alarm. This alarm does not just trigger inflammation; it initiates a vicious, self-amplifying cycle of cellular senescence, tissue fibrosis, and follicle destruction-a cycle that may explain why ovarian aging often feels like a one-way street. Therapeutically, we move beyond mere symptom management to explore strategies for resetting this inflammatory clock. We dissect both direct "brakes"-novel small molecules that silence cGAS or STING-and upstream "shields" that protect cellular powerplants and genome integrity. Most provocatively, we introduce the concept of "signal reprogramming": not just shutting down the pathway, but cleverly rewiring its output to favor repair over destruction. By repositioning cGAS-STING from a simple sensor to the central processor of ovarian aging, this review charts a course for a new class of therapeutics aimed at preserving ovarian function, not just managing its loss. The goal is no less than transforming our approach to women's reproductive longevity.

Macrophages are essential components of the innate immune system and exhibit remarkable functional plasticity, playing pivotal roles in inflammatory responses, maintenance of tissue homeostasis, and the initiation and progression of tumors as well as a wide range of other diseases. Accumulating evidence in recent years has demonstrated that, in addition to classical transcriptional regulation, post-transcriptional regulation is equally critical for macrophage fate determination and functional specialization. RNA-binding proteins (RBPs), as central regulators of post-transcriptional gene control, orchestrate a sophisticated and dynamic gene expression network by modulating RNA splicing, nucleocytoplasmic transport, stability and decay, translational efficiency, RNA epigenetic modifications, liquid-liquid phase separation, and chromatin-associated processes. Substantial experimental data indicate that RBPs are deeply involved in macrophage polarization, survival and programmed cell death, as well as metabolic reprogramming, thereby shaping the magnitude of inflammatory responses, immune suppressive states, and remodeling of the tumor microenvironment. In this review, we systematically summarize the molecular mechanisms by which RBPs regulate macrophage functions, with particular emphasis on their roles in inflammatory disorders, cancer, and metabolism-related diseases. We also highlight recent advances in the coordinated regulation of macrophage biology by RBPs in conjunction with RNA modifications, including m⁶A, m⁵C, and ac⁴C, as well as noncoding RNAs. Finally, we discuss the opportunities and challenges of targeting RBPs as emerging immunotherapeutic strategies, underscoring their potential in reprogramming the tumor immune microenvironment and enhancing the efficacy of immunotherapy, thereby providing a theoretical framework for the development of precise immune intervention approaches.

Beige adipocytes have emerged as an attractive therapeutic target for metabolic disease due to their inducible thermogenic capacity and developmental plasticity. However, despite substantial advances in understanding the molecular pathways that activate thermogenesis, most thermogenic strategies have shown limited durability in pathological settings. This article integrates recent discoveries in adipocyte cell biology to argue that thermogenic failure reflects a loss of cellular competence rather than insufficient stimulation. We review emerging evidence demonstrating that mitochondrial capacity, intracellular signaling fidelity, and vesicle trafficking impose critical cell-intrinsic constraints on beige adipocyte function, particularly in obesity and aging. These insights highlight why chronic, systemic activation strategies often fail to produce sustained metabolic benefits. Drawing on principles from developmental biology, we propose that restoring thermogenic function will require precision control of adipocyte cell state, including spatially and temporally defined modulation of signaling pathways. Emerging technologies enabling reversible, cell-targeted control of adipocyte function, coupled with human cell-based models, offer new opportunities to overcome current limitations. Together, this perspective emphasizes that beige adipocytes are not merely thermogenic effectors, but dynamic cellular systems whose therapeutic potential depends on maintaining or restoring adaptive plasticity.

Background: Hao-Fountain syndrome (HAFOUS) is a rare autosomal dominant neurodevelopmental disorder caused by pathogenic USP7 variants. A diagnostic blood DNA methylation episignature has been established, yet the broader regulatory consequences of USP7 haploinsufficiency and their tissue specificity remain incompletely characterized.

Methods: We performed genome-wide DNA methylation profiling, RNA sequencing, and cis expression quantitative trait methylation (eQTM) analysis in whole blood (n = 9) and patient-derived skin fibroblasts (n = 4). Differential methylation was assessed and methylation-expression coupling within ±250 kb of each DMR. DMRs were further interpreted using BCOR, H2AK119ub1, and H3K27me3 ChIP-Rx datasets from neural models.

Results: Blood reproduced the established USP7 hypermethylation episignature and yielded 17 significant DMRs, accompanied by modest numbers of differentially expressed genes and eQTMs. Fibroblasts displayed internally coherent regulatory patterns, including 2,143 nominal DMRs, 310 differentially expressed genes, and 559 significant eQTMs. Convergent methylation-expression changes prominently involved the HOXB cluster (HOXB3, HOXB5, HOXB6). Both blood- and fibroblast-derived DMRs showed significant enrichment for BCOR- and H2AK119ub1-marked regions, consistent with disruption of non-canonical PRC1.1-associated chromatin. Cross-tissue comparison revealed limited overlap, supporting marked tissue specificity in methylation-expression relationships.

Conclusion: USP7 haploinsufficiency is associated with a restricted set of regulatory loci enriched within PRC1-associated chromatin domains. Fibroblasts revealed coherent methylation and expression changes at developmental genes, whereas blood captured the diagnostic episignature and a smaller set of downstream regulatory alterations. Together, this dual-tissue integrative analysis refines the molecular consequences of reduced USP7 dosage and provides a framework for future mechanistic studies in disease-relevant cellular models.

Lung development is a complex and precisely regulated process of continuously branching morphogenesis, the core of which lies in the directed differentiation of diverse cell types and the dynamic intercellular interaction network. This review systematically delineates the differentiation pathways of major cellular lineages during pulmonary development, with a particular focus on the dual functions of epithelial cells as the core regulatory hub of the microenvironment. These cells not only dominate the spatial patterning of lung branching morphogenesis but also orchestrate the developmental fates of key cell types through multiple signaling cues. Furthermore, this review discusses the regenerative properties of lung-resident stem cells and the interaction patterns between various cell types and epithelial cells. These insights not only provide an important theoretical framework for elucidating the molecular regulatory network of lung development but also offer novel ideas for the optimization of strategies in lung regenerative medicine and the precision intervention for lung-related diseases.

Psychiatric disorders are increasingly viewed as network-level brain diseases resulting from disruptions in neural signaling across various hierarchies, including molecular, synaptic, circuit, and systems levels. Evidence indicates that receptor dysregulation, abnormal intracellular pathways, and changes in ion channel activity lead to widespread network dysconnectivity, resulting in cognitive, emotional, and behavioral deficits. This review integrates advancements in genomics, transcriptomics, connectomics, and computational modeling to establish a framework for understanding signaling abnormalities in major psychiatric disorders. Further, this study investigates essential molecular and cellular processes such as synaptic plasticity, receptor-mediated communication, intracellular signaling cascades, and neuroimmune interactions, and connects these to disturbances in oscillatory dynamics, circuit architecture, and overall brain network organization. Additionally, neuroimaging and graph-theoretic studies consistently demonstrate an excitation-inhibition imbalance, atypical synaptic pruning, impaired oscillatory synchrony, and maladaptive connectivity within networks, including the default mode, salience, and fronto-limbic systems, across schizophrenia, depression, bipolar disorder, anxiety, and autism spectrum disorders. Moreover, genetic and epigenetic variations in signaling genes, such as CACNA1C, GRIN2B, and DISC1, along with developmental and environmental factors, contribute to network vulnerability and clinical heterogeneity. Emerging artificial intelligence and multimodal integration methods facilitate the identification of individualized "signaling fingerprints," which connect molecular perturbations to systems-level dysfunction. This research enhances precision psychiatry and guides targeted interventions based on neuromodulation, molecular mechanisms, and biomarkers.