Journal of Cellular Physiology最新文献

Growing evidence has established the imprinted gene neuronatin (NNAT) as a key regulator in human metabolic disorders, particularly obesity and type 2 diabetes. Its expression is prominently detected in major neuroendocrine and metabolic tissues, including the hypothalamus, pancreas, adipose tissue, and skeletal muscle. NNAT orchestrates diverse cellular processes through its regulation of intracellular calcium dynamics and pathological insulin secretion. Notably, NNAT exhibits nutrient-responsive regulation and is a crucial modulator of glucose homeostasis, adaptive thermogenesis, and overall energy balance. These pleiotropic functions position NNAT as an attractive therapeutic target for obesity-related metabolic disorders. This comprehensive review systematically evaluates the multifaceted roles of NNAT in metabolic regulation, with a particular focus on its tissue-specific mechanisms in both physiological and pathological states while integrating the current understanding of its contributions to systemic metabolic homeostasis.

Research in the past decade has elucidated the explicit role of the immune system in the pathophysiology of osteoporosis. Recent studies have further unraveled the complex interactions between bone and immune cells and explored safe, effective immunomodulatory approaches—such as probiotics—for preventing and managing osteoporosis. As a result, various immune factors have continuously been discovered to play specific roles in maintaining bone homeostasis. The role of Tregs in the context of postmenopausal osteoporosis (PMO) is already well established. While Foxp3⁺ Tregs are mostly matured in the thymus (tTregs), some are also produced from Foxp3⁻CD4⁺ T-cell precursors in the peripheral tissues (i.e., pTregs). Notably, the specific role of pTregs and tTregs in PMO remains to be elucidated. Here, we reveal that estrogen-deficient inflammatory conditions in PMO disrupt the balance of tTregs and pTregs. Interestingly, within pTregs, the population of RORγT⁻ pTregs and RORγT⁺ pTregs is further altered, along with simultaneous expansion of Th17 cells—likely through the conversion of RORγT⁻ pTregs into Th17 cells. Notably, supplementation with Lactobacillus acidophilus (LA) restores the homeostasis of RORγT⁻ pTregs and Th17 cells in a butyrate-mediated manner. Moreover, it was observed that butyrate-primed RORγT⁻ pTregs have reduced osteoclastogenic potential. Collectively, our findings for the first time reveal the pivotal role of gut resident RORγT⁻ pTregs–Th17 cell axis in the pathophysiology of PMO.

This study explored the role of telomere attrition in astrocytic senescence by pharmacologically inhibiting telomerase activity in human induced pluripotent stem cell-derived astrocytes. Treatment with the telomerase inhibitor BIBR1532 (BIBR) during differentiation induced hallmark features of senescence, including nuclear lamina abnormalities, enhanced senescence-associated β-galactosidase activity, increased replication arrest and DNA damage, altered reactive oxygen species homeostasis in mitochondria, accompanied by significant shortening of relative telomere length. Despite these senescence related characteristics, BIBR-treated astrocytes exhibited limited changes in the expression of senescence-associated secretory phenotype-related genes. Moreover, their key functional properties, such as glutamate uptake, synaptic vesicle clearance, mitochondrial membrane potential and morphology remain comparable to those of control astrocytes. These findings suggest that the presence of classical senescence markers does not necessarily lead to functional impairment and that BIBR-induced senescence in astrocytes may represent an early or transitional phase, where classical senescence markers emerge without substantial functional decline. Our results reinforce the notion that while telomere attrition is a major cellular senescence driver, its onset may not be attributed to a single stressor but rather to a complex interplay of cellular stress pathways. This study provides valuable insights into the mechanisms underlying astrocytic senescence and underscores the need for further research on the molecular basis of its occurrence and functional implications.

Osteoporosis, fragility fractures, and pathologic fractures are increasingly recognized as long-term complications in cancer survivors. Women are more susceptible to bone loss than men, and breast cancer is the most common malignancy in women. In this population, bone health is a critical concern due to both therapy-induced bone loss and a high propensity for skeletal metastasis. Antiresorptive agents are widely used; however, their known adverse effects and limited capacity to rapidly reduce fracture risk in high-risk individuals have led to growing support for the early use of osteoanabolic therapies. Among these, intermittent administration of parathyroid hormone [PTH (1–34)] has demonstrated clinical efficacy in reducing fracture risk by activating the PTH 1 receptor in osteoblasts. However, its safety and mechanistic relevance in the context of breast cancer remain poorly understood. This review outlines the osteoblast-specific signaling pathways of PTH (1–34) and includes our recent research that identified p21-activated kinase 4 as a downstream effector linking canonical cyclic adenosine monophosphate-protein kinase A signaling to Wnt/β-catenin activation. Additionally, it explores the potential implications of PTH (1–34) in the context of breast cancer-related bone metastasis.

Skin aging is a complex biological process driven by the dynamic interplay of cellular senescence, molecular dysfunction, and microenvironmental remodeling. The aging microenvironment acts as both a consequence and a driver of skin aging, creating a vicious cycle that exacerbates inflammation, oxidative stress, and barrier dysfunction. An in-depth exploration of the aging skin microenvironment plays a revolutionary role in the field of skin anti-aging and holds promise for the discovery of novel and feasible targets for skin anti-aging. This review systematically elaborates the aging skin microenvironment through a framework of six interconnected components: (1) inflammaging and immune cell dysfunction, (2) extracellular matrix dysregulation, (3) intercellular communication and extracellular vesicles defect, (4) physical microenvironmental alterations, (5) stem cell exhaustion, and (6) microbiome dysbiosis. These components collectively establish a self-reinforcing network that perpetuates structural degradation, functional decline, and impaired regenerative capacity.