FASEB JOURNAL
FASEB JOURNAL(英文缩写 FASEB J),ISSN 0892-6638,eISSN 1530-6860 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-09-27 至 2026-09-27，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 5.834 | Q1 |
| 2022 | 4.800 | Q1 |
| 2023 | 4.400 | Q1 |
| 2024 | 4.200 | Q1 |
| 2025 | 4.300 | Q1 |
FASEB JOURNAL 最新收录文献
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1. Targeting Oxidative and Immune Dysregulation in Wound Healing via Gold Nanoparticle Conjugate Chitosan.
PMID:期刊:日期:2026-10-15A novel gold nanoparticle-chitosan (AuNP@chitosan) composite is introduced as a potent biointerface modulator for burn trauma care. In this study, the unique interfacial characteristics of the composite are linked to its therapeutic activity, and its effects on endothelial function and immune response in severe bleeding and inflammatory models are examined. AuNP@chitosan synthesis was verified using FTIR and fluorescence, and its effects were assessed in TNF-α-induced HUVECs, LPS-stimulated macrophages, and an animal model. In vitro, AuNP@chitosan protects TNF-α-injured human endothelial cells (HUVECs) by restoring thrombomodulin expression, reducing ROS, and relieving the upregulated hypoxia-adaptive markers (HIF-1α and fibronectin). Concurrently, in LPS-stimulated RAW 264.7 macrophages, it suppresses pro-inflammatory mediators (TNF-α and IL-6) while preserving COX-1 and enhancing IL-10 production. These cell-specific responses reflect distinct but complementary mechanisms, vascular protection and immune regulation, which were further validated in a rat burn model. In vivo application of AuNP@chitosan dressings significantly reduced infiltration of CD4, CD8, and CD68 immune cells in wound tissue, supporting the translational relevance of the dual in vitro findings. The integrated cell and animal studies demonstrate that AuNP@chitosan acts via redox and immune modulation to promote a pro-healing wound environment.
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2. {"_":"Cyp27b1 Deficiency Impairs Ovarian Development Through Disrupted 1,25(OH)D Regulation of Lipid Metabolism and Redox Homeostasis.","sub":["2","3"]}
PMID:期刊:日期:2026-10-15Female reproductive disorders are closely associated with ovarian oxidative stress and lipid dysregulation, but the upstream triggers remain poorly defined. In this study, we found that Cyp27b1, a key mitochondrial enzyme that catalyzes the conversion of 25-hydroxyvitamin D (25(OH)D) to 1,25-dihydroxyvitamin D (1,25(OH)D), is an important regulator of ovarian lipid homeostasis and redox balance. In the cyp27b1 zebrafish model, cyp27b1 deletion impaired ovarian development and caused mitochondrial dysfunction and oxidative stress, all of which were alleviated by exogenous 1,25(OH)D treatment. Lipidomic analysis revealed an abnormal accumulation of triglycerides (TG) and diglycerides (DG) in the knockout group, while phosphatidylcholine (PC) and phosphatidylethanolamine (PE), key membrane lipid components, were significantly reduced, disrupting membrane integrity and energy homeostasis. Dual-luciferase reporter assays showed that 1,25(OH)D increased pnpla2 promoter activity through a predicted vitamin D response element, thereby promoting TG hydrolysis in cyp27b1 ovaries. In contrast, insufficient 1,25(OH)D production increased Pparγ expression and promoted abnormal lipid deposition. Exogenous 1,25(OH)D treatment reduced lipid deposition and restored Pparγ and Pnpla2 expression toward normal levels. In conclusion, our findings suggested that Cyp27b1 deficiency impaired ovarian development through lipid overload associated oxidative damage. These results linked impaired Cyp27b1 mediated 1,25(OH)D production to ovarian lipid metabolic disturbance and redox imbalance. Lipid metabolic changes involving pnpla2 and pparγ may represent potential regulatory targets for 1,25(OH)D deficiency associated ovarian pathologies.
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3. Baicalein Ameliorates Postmenopausal Osteoporosis With Iron Accumulation by Inhibiting Osteoclastogenesis via Nrf2 Activation.
PMID:期刊:日期:2026-10-15Postmenopausal osteoporosis (PMOP) is frequently complicated by iron accumulation, which exacerbates bone loss. Baicalein, a natural flavonoid with iron-chelating and antioxidant properties, has shown bone-protective effects, but its role in iron-overloaded PMOP remains unclear. This study investigated whether baicalein ameliorates iron-accumulated PMOP by inhibiting osteoclastogenesis via Nrf2 activation. In vitro, bone marrow-derived macrophages (BMMs) were induced into osteoclasts with RANKL under iron overload. Baicalein (10 μM) suppressed osteoclast differentiation, F-actin ring formation, and bone resorption, reduced intracellular and mitochondrial ROS, lowered Fe and total iron content, and upregulated Nrf2 nuclear translocation and HO-1 expression. These effects were abrogated by the Nrf2 inhibitor ML385 or Nrf2 siRNA. In vivo, an ovariectomized (OVX) mouse model with iron dextran injection (100 mg/kg/week) was used. Oral baicalein treatment (100 mg/kg/day) significantly prevented bone loss, improved bone microarchitecture and biomechanical properties, reduced iron deposition in bone, liver and spleen, lowered serum ferritin and bone ROS, and activated Nrf2 signaling in bone tissue. Co-administration of ML385 reversed these protective effects. Collectively, baicalein ameliorates iron-accumulated postmenopausal osteoporosis by activating the Nrf2 pathway, thereby inhibiting osteoclast differentiation and bone resorption. Baicalein represents a promising multi-target candidate for treating PMOP, especially in patients with concomitant iron accumulation.
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4. NR4A1-Driven Granulosa Cell Ferroptosis Contributes to Obesity-Related Ovarian Dysfunction and Metformin-Mediated Ovarian Protection.
PMID:期刊:日期:2026-10-15Obesity triggers ovarian dysfunction and female infertility accompanied by granulosa cell damage. Ferroptosis, iron-dependent lipid peroxidation-mediated cell death, participates in multiple reproductive diseases, yet the molecular cascade linking metabolic obesity to granulosa ferroptosis remains undefined. Using high-fat diet obese mice, primary human granulosa cells from obese infertile patients, and KGN cell lines, we identified the nuclear receptor NR4A1 as a key mediator of obesity-induced ferroptosis downstream of PI3K/AKT signaling. Elevated NR4A1 was associated with upregulated ACSL4 and suppressed GPX4, accompanied by iron overload, lipid peroxidation, and mitochondrial collapse, impairing folliculogenesis and oocyte quality. Metformin reduced NR4A1 activation in association with PI3K/AKT signaling modulation, thereby attenuating ferroptotic injury and contributing to the restoration of ovarian function. In vivo NR4A1 agonist administration attenuated the protective effects of metformin, while ovarian-specific NR4A1 knockdown alleviated HFD-triggered ovarian ferroptosis. Single-cell RNA-seq further suggested that metformin remodels oocyte redox and folliculogenic transcriptional networks. These findings support a role for the PI3K/AKT-NR4A1 signaling pathway in driving ferroptosis during obesity-related ovarian dysfunction and suggest a potential anti-ferroptotic mechanism of metformin in this context.
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5. Association of Neutrophil Percentage-to-Albumin Ratio (NPAR) With Pathological Features and Long-Term Prognosis in Diabetic Kidney Disease: A Cohort Study.
PMID:期刊:日期:2026-10-15Growing evidence highlights the central role of inflammation in the onset and progression of DKD. In this study, we investigate the association between the neutrophil percentage-to-albumin ratio (NPAR) and clinicopathological features, as well as long-term renal outcomes, in patients with diabetic kidney disease (DKD). Three hundred five biopsy-confirmed DKD patients with baseline eGFR ≥ 15 mL/min/1.73 m were retrospectively enrolled in this study. Baseline clinical and pathological characteristics were compared across NPAR quartiles. The primary outcome was 2-year DKD progression, defined as a > 40% increase in serum creatinine, end-stage renal disease, or all-cause mortality. Multivariable logistic regression, restricted cubic spline (RCS) analysis, and subgroup analyses were conducted to examine the association between the NPAR and kidney outcomes. Subsequently, a prognostic nomogram was constructed for DKD patients incorporating NPAR to stratify individual risk. Higher baseline NPAR quartiles were significantly associated with renal dysfunction and advanced renal pathological lesions. In a subset of renal biopsy specimens, MPO immunostaining demonstrated increased renal neutrophil infiltration in patients with higher NPAR quartiles. Renal MPO expression was positively correlated with mesangial expansion, interstitial fibrosis, and tubular atrophy. Among patients with complete follow-up, 65.3% developed the composite kidney outcome. Compared with the lowest NPAR quartile, multivariable-adjusted odds ratios (95% CIs) for kidney outcomes were 1.68 (0.36-8.15), 6.21 (1.35-33.55), and 6.88 (1.27-46.86) for Q2, Q3, and Q4, respectively. RCS analysis indicated a nonlinear association between NPAR and kidney outcomes, with risk increasing sharply above an NPAR value of 1.38. Subgroup analyses identified significant interactions between NPAR and Kimmelstiel-Wilson nodules as well as SGLT2 inhibitor use on kidney outcomes. A prognostic model incorporating NPAR quartiles, age, total cholesterol, eGFR, and interstitial fibrosis demonstrated good discrimination (AUROC 0.863). In conclusion, elevated NPAR is associated with increased renal neutrophil infiltration, more severe histopathological injury, and adverse renal outcomes in patients with DKD, and independently predicts long-term renal progression.
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6. Ten-Eleven Translocation Enzymes Control the Rate and Mode of Retinal Progenitor Cell Division in the Developing Retina.
PMID:期刊:日期:2026-10-15Ten-Eleven Translocation (TET) enzymes are responsible for DNA demethylation and epigenetic regulation. Inactivation of TET enzymes in retinal progenitor cells (RPCs) leads to the emergence of a non-functional retina, resulting in blindness. However, it was not known how the inactivation of TET enzymes in RPCs affects their immediate function. To this end, we investigated TET-deficient RPCs in the developing retina using various approaches including EdU cell proliferation assay, immunohistochemistry, bulk RNA-seq, and snRNA-seq. We found that inactivation of TET enzymes in RPCs results in slow retinal growth. The number of dividing TET-deficient RPCs in these retinas is lower, whereas the number of non-dividing cells derived from them is significantly higher compared to controls. This phenomenon could be explained by the predominantly asymmetric division of TET-deficient RPCs, which is characteristic of late progenitor cells. At the same time, TET-deficient RPCs maintained a high rate of proliferation, continuing to divide even during late stages of retinal development, a phase during which cell division could no longer be detected in the control samples. A high rate of proliferation is a characteristic typically associated with early progenitor cells. We showed that retinas emerging from the activity of these TET-deficient RPCs are less developed and less complex, likely due to the mixed phenotype of the RPCs. Thus, our findings suggest that the activity of TET enzymes in RPCs is necessary to prevent mixing of their early and late phenotypes, a condition that is critical for normal retinal development.
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7. Brain-Kidney Axis Dysfunction in Intracerebral Hemorrhage: Mechanisms and Interventions.
PMID:期刊:日期:2026-10-15Intracerebral hemorrhage (ICH), the most fatal stroke subtype, causes severe acute brain injury and frequent multiple-organ dysfunction, with renal impairment representing a common and severe complication. ICH patients are susceptible to secondary acute kidney injury (AKI), and many of those who progress to chronic kidney disease (CKD) or even end-stage renal disease. Although these adverse clinical outcomes are closely associated with the bidirectional brain-kidney axis, the precise molecular and pathological mechanisms underlying ICH-related AKI and subsequent CKD progression remain poorly elucidated. The AKI and CKD after ICH are mediated by multiple interconnected pathological mechanisms governed by the dysregulated brain-kidney axis, including sympathetic nervous system (SNS) overactivation, excessive stimulation of hypothalamic-pituitary-adrenal (HPA) axis and the renin-angiotensin-aldosterone system (RAAS), systemic inflammation, oxidative stress injury, and uremic toxin accumulation. These mediators fuel a bidirectional pathogenic cycle between the brain and kidney, while shared microvascular vulnerability as well as hemodynamic characteristics of both organs facilitate such inter-organ crosstalk. Brain-kidney axis dysfunction represents the core pathogenesis underlying ICH-induced secondary renal impairment. Clinical interventions should adopt a brain-kidney co-protection strategy, combining neuroprotective, renoprotection, and targeted pathway-based therapies.
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8. ADP-Ribosylation Factor Guanine Nucleotide Exchange Factor 3 Aggravates Cisplatin-Induced Acute Kidney Injury by Impairing Mitochondrial Fatty Acid Oxidation.
PMID:期刊:日期:2026-09-30Acute kidney injury lacks definitive therapeutic options and clear molecular mechanisms. The proximal tubule demands high energy primarily derived from mitochondrial fatty acid beta-oxidation. ADP-ribosylation factor guanine nucleotide exchange factor 3 (Arfgef3) plays a role in tumor-associated diseases, but its function in nephrotoxicity remains unclear. We hypothesized that this exchange factor contributes to cisplatin-induced AKI by disrupting peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α)-mediated mitochondrial function and fatty acid oxidation. We utilized global knockout mice and human kidney 2 cells to investigate this exchange factor in cisplatin-induced injury in vivo and in vitro. Renal function was evaluated using biochemical markers and histopathological scores. Mitochondrial integrity and respiratory capacity were measured via transmission electron microscopy and Seahorse analysis. Intracellular lipid accumulation, key fatty acid oxidation enzymes, and physical interactions with PGC-1α were evaluated alongside small-molecule agonist rescue experiments. Arfgef3 was upregulated in renal tubular epithelial cells after cisplatin exposure. Genetic Arfgef3 knockout in mice significantly attenuated cisplatin-induced elevations in serum creatinine, blood urea nitrogen, tubular necrosis, inflammation, and cellular apoptosis. Furthermore, loss of this protein preserved mitochondrial ultrastructure, restored cellular adenosine triphosphate production, and reversed the suppression of key fatty acid oxidation enzymes. Mechanistically, co-immunoprecipitation confirmed a direct interaction between Arfgef3 and PGC-1α. Activating the coactivator with the agonist ZLN005 substantially rescued the aggravated mitochondrial damage and lipid accumulation caused by Arfgef3 overexpression. Arfgef3 promotes cisplatin-induced AKI through PGC-1α-mediated mitochondrial dysfunction and impaired fatty acid oxidation. Targeting this novel signaling pathway may represent a promising therapeutic strategy for preventing or treating cisplatin-associated nephrotoxicity.
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9. ADP Inhibits Macrophage Senescence via the AMPK/KLF10 Pathway in Systemic Lupus Erythematosus.
PMID:期刊:日期:2026-09-30Lupus nephritis (LN) is a critical complication of systemic lupus erythematosus (SLE) and a leading cause of mortality in those affected. Abnormal energy metabolism of macrophages is closely associated with LN pathogenesis. Adenosine diphosphate (ADP) is known to regulate macrophage proinflammatory function; however, its specific role in SLE progression remains unexplored. We employed a spontaneous SLE mouse model and an integrated transcriptomic and metabolomic approach to investigate the effect of ADP on SLE disease progression and macrophage function. Our study revealed that ADP stimulates the AMPK signaling pathway, curtails macrophage senescence, and diminishes the release of senescence-associated secretory phenotype factors, ultimately alleviating SLE progression. Mechanistically, ADP promotes KLF10 expression, which binds to Sirtuin1 to facilitate deacetylation at the promoter region of Cdkn1a in macrophages. This process leads to reduced p21 expression and macrophage senescence. Collectively, the findings uncover a novel regulatory role of ADP in the pathogenesis of SLE and macrophage senescence, indicating its potential as a target for treatment.
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10. G Protein-Coupled Receptor 68 Promotes the Progression of Triple-Negative Breast Cancer and Cuproptosis Resistance via the MEK/ERK Signaling Pathway.
PMID:期刊:日期:2026-09-30Cuproptosis is a type of cell death that depends on the energy production process inside cells, and it is important in cancer treatment. This study aimed to identify cuproptosis-associated genes in triple-negative breast cancer (TNBC) and reveal regulatory pathways. We applied weighted gene co-expression network analysis to screen gene expression data from TNBC patients. Cuproptosis-associated genes were identified at the intersection of the co-expression modules and the cuproptosis gene dataset. G protein-coupled receptor 68 (GPR68) was identified as a cuproptosis-associated gene that is highly expressed in TNBC cells. Knockdown of GPR68 inhibited TNBC cell growth, migration, and invasion. The knockdown of GPR68 enhanced cuproptosis in TNBC cells when stimulated with ES-Cu, leading to an accumulation of cellular copper. This effect was reversed by the copper chelator tetrathiomolybdate. Correlation analysis verified that GPR68 regulates glutaminase (GLS) expression in TNBC cells. GLS knockdown reversed the promoted role of GPR68 in TNBC progression and the inhibitory role of GPR68 in TNBC cell cuproptosis. We further investigated the role of GPR68 in TNBC through pathway enrichment analysis, which revealed significant enrichment in the mitogen-activated protein kinase (MAPK) signaling pathway. GPR68 overexpression increased the levels of ERK phosphorylation. The ERK signaling pathway inhibitor, Trametinib, blocked the effects of GPR68 on TNBC progression and cuproptosis. GPR68 knockdown hindered TNBC development and induced cell cuproptosis by regulating the MEK/ERK signaling pathway, which is linked to GLS. This study provides new insights into developing cuproptosis targets for TNBC treatment.