BACKGROUND:Intracerebral hemorrhage (ICH) is the most severe subtype of stroke and currently lacks effective therapies. PANoptosis, a novel programmed cell death mode, plays an important role in ICH. Rhubarb has shown neuroprotective potential in ICH, but its mechanisms remain unclear. PURPOSE:To investigate whether rhubarb attenuates PANoptosis in microglia after ICH by regulating small nucleolar RNA (snoRNA). METHODS:ICH was induced in mice by collagenase VII injection and treated with rhubarb (0.6, 1.2, 2.4 g/kg, gavage). Neurological function, histopathology, and blood-brain barrier integrity were evaluated. snoRNA sequencing and RT-qPCR were used to identify differentially expressed snoRNAs. Inflammatory cytokines and PANoptosis-related proteins were assessed by ELISA and Western blot. BV2 microglia were treated with rhubarb-containing serum, and Snord17 was knocked down to explore functional mechanisms. RESULTS:Rhubarb significantly improved neurological scores, reduced neuronal damage and blood-brain barrier disruption, and inhibited IL-1β, TNF-α, and IL-6 expression. ICH markedly decreased Snord17 expression, while rhubarb reversed this change. Rhubarb also suppressed PANoptosis markers (ZBP-1, RIPK3, NLRP3, Caspase-3). In vitro, rhubarb reduced oxidative stress and inflammation in BV2 cells. Snord17 knockdown activated the p53 signaling pathway and promoted PANoptosis. CONCLUSION:Rhubarb ameliorates neurological deficits and neuroinflammation after ICH by upregulating Snord17, thereby suppressing PANoptosis.

BACKGROUND:Liangfu Dripping Pills (LFDP) are a pharmaceutical formulation derived from the Liangfu Formula, a classic traditional Chinese medicine (TCM) prescription with well-documented clinical efficacy for the treatment of gastric ulcers. Nevertheless, the in vivo processes of its active constituents and the underlying mechanisms of its anti-ulcer effects remain to be fully elucidated. OBJECTIVE:To reveal the active ingredients and potential mechanisms of LFDP in exerting anti-acute gastric ulcer effects through spectrum-effect relationship and pharmacokinetics-pharmacodynamics (PK-PD) Model. METHODS:An ethanol-induced acute gastric ulcer model was established in rats. The spectrum-effect correlation between the differentially migrated constituents of LFDP and gastric ulcer indicators was analyzed to screen PK/PD markers. Differential pharmacokinetic characteristics were evaluated with respect to dosage and biological state (normal vs. gastric ulcer). An integrated multi-constituent PK-PD model was established, and potential regulatory pathways of LFDP were verified by immunoblotting and RT-qPCR. RESULTS:LFDP dose-dependently ameliorated gastric mucosal degeneration and necrosis in rats with ethanol-induced acute gastric ulcers. Twenty-seven plasma migrated constituents correlated closely with increased levels of EGF, NO, SOD and decreased TNF-α, GAS, MDA (VIP>1). The in vivo exposure levels of caryophyllene oxide, cyperenone, rhamnocitrin, and galangin-3-O-methyl ether increased in a significant dose-dependent manner. α-terpineol, benzylacetone, caryophyllene oxide, cyperenone, galangin, rhamnocitrin, or galangin-3-O-methyl ether in gastric ulcer rats exhibited increased absorption rate, higher exposure, slower clearance, and longer retention. Multi-indicator constituents had the smallest EC50 and Ke0 vs. EGF, indicating strongest affinity, slower regulation, and longer duration. LFDP significantly upregulated EGF and EGFR protein and mRNA levels in ulcerated gastric tissue (P < 0.05). CONCLUSION:LFDP exerted a pronounced protective effect against ethanol-induced acute gastric ulcer, which was closely correlated with the systemic exposure of its flavonoid and volatile constituents. Multiple constituents displayed distinct pharmacokinetic profiles in healthy and gastric ulcer pathological states. The regulation of the EGF/EGFR signaling pathway represents a critical potential mechanism for LFDP to exert its protective effect against acute gastric ulcers.

Novel zinc oxide nanoflowers (ZnO NFs) were synthesized using the aqueous extract of Zanthoxylum simulans. The green synthesized Zs-ZnO NFs were characterized using FT-IR, XPS, XRD, HR-TEM, EDAX, DLS, and zeta potential (ZP) analysis to confirm the physicochemical properties. HR-TEM analysis exposed the flower-like morphology with uniform size. The XPS analysis exposed the elements present in the Zs–ZnO NFs. Further, the Zn element exhibited two binding energy peaks at 1021.41 and 1044.50 eV. The purity of Zs–ZnO NFs was confirmed using EDAX analysis. The Zs–ZnO NFs displayed bactericidal properties against the tested pathogens. To evaluate the effectiveness of Zs–ZnO NFs against dental pathogens via MIC, antibacterial, biofilm ring formation, and TTC assays were performed. A concentration-dependent biofilm inhibition was also observed against Staphylococcus aureus and Streptococcus mutans upon treatment with Zs–ZnO NFs, and it was confirmed using a 2.5D fluorescence imaging technique. A 100 µg/mL of Zs–ZnO NFs treatment displayed bacterial cell death, which was confirmed via dual staining. Furthermore, Zs–ZnO NFs induced protein leakage was observed upon treatment with 100 µg/mL concentration against the pathogens. Cytotoxicity of Zs–ZnO NFs was confirmed using HUVECs cells. Overall, the synthesized Zs–ZnO NFs exhibits efficient bactericidal, antibiofilm and biocompatible properties.

Transforming herbal-derived small molecules into nano-formulations represents a crucial interdisciplinary strategy for modernizing traditional Chinese medicine (TCM). Glycyrrhizic acid (GL), renowed for its well-documented clinical efficacy and intrinsic amphiphilic structure, exemplifies the successful conversion of TCM compounds into functional nanobiomaterials. A systematic analysis of GL’s extensive evolution from a therapeutic agent to a multifunctional biomaterial is critical to accelerating TCM modernization, yet remains insufficiently reviewed. In this article, we comprehensively reconstruct and elucidate GL’s evolutionary trajectory from a conventional pharmacological molecule to an advanced nanobiomaterial. First, we analyze the molecular structure of GL alongside its in vivo metabolic pathways. Next, we summarize the diverse pharmacological activities of GL as a small-molecule drug. Subsequently, we trace the development of GL-based biomaterials over the past five decades, classifying them into six principal categories: nanoparticles, micelles, hydrogels, liposomes, metal-organic frameworks, and nanocrystals (NCs). Each category is further subdivided and systematically analyzed. We provide an in-depth discussion from multiple perspectives, including GL’s self-assembly behavior, ligand functionalities, and potential for biointerface modulation, covering aspects such as preparation methods, design principles, performance advantages, and current limitations. Finally, grounded in clinical translational needs, we identify current challenges, propose feasible solutions, and outline future research directions for GL-based biomaterials.

Traumatic brain injury (TBI) causes acute neuronal and vascular damage accompanied by intense neuroinflammation, yet current surgical and pharmacological interventions yield limited long-term benefits. Embryonic stem cell-derived small extracellular vesicles (ESC-sEV) carry potent pro-repair signals but suffer from poor brain targeting and rapid clearance in the acute inflammatory window. To address these critical limitations, we engineered an injectable ESC-sEV-glycyrrhizic acid (GA) co-assembled hydrogel (EG-gel) in which sEVs act as a functional gel factor interpenetrating GA nanoscaffolds. GA molecules were self-assembled into nanoscaffolds via hydrogen bonding, with polar head groups coordinating to sEV membranes while hydrophobic cores insert into lipid bilayers, yielding a robust, hierarchical matrix. EG-gel exhibited brain-compatible mechanical properties, rapid self-healing, shear-thinning injectability, and strong tissue adhesion, which collectively enhance local sEV accumulation at the lesion site. In a mouse TBI model, the EG-gel showed superior neuroprotective effects and functional recovery outcomes compared with the GA-gel. Transcriptomics combined with experimental validation confirmed a spatiotemporal synergistic mechanism: GA mediated early inflammatory suppression and immune microenvironment stabilization, while co-assembled sEVs drove angiogenesis and neuronal repair. Therefore, the EG-gel played a synergistic role in establishing a sequential "first anti-inflammatory, then vasoneural regeneration" microenvironment, thereby promoting neuroprotection after TBI. This work highlights the EG-gel as an up-and-coming candidate for translational therapy in TBI.

Acute liver failure (ALF) is a life-threatening clinical syndrome characterized by high-grade inflammation and multi-organ failure. Our previous study shows that targeting the M2 isoform of pyruvate kinase (PKM2) to inhibit macrophage inflammation may be a promising strategy for ALF treatment. however, the mechanism by which PKM2 regulates the inflammatory response is unclear. Here we demonstrate that PKM2 contributes to ALF by modulating NLRP3-mediated pyroptosis activation in liver macrophages. The specific knockout of PKM2 in myeloid cells reduces mortality and alleviates hepatic injury in D-galactosamine/LPS-induced ALF mice. Single-cell transcriptome analysis suggests that NLRP3 inflammasome activation of macrophages involves in ALF, knockout of PKM2 in macrophages reduces the expression of NLRP3, and activation of pyroptosis. Pharmacological inhibition of the PKM2 nuclear translocation, but not glycolytic activity, protects mice from ALF. Pharmacological and genetic inhibition of PKM2 attenuates NLRP3-mediated pyroptosis activation and consequently reduces the release of IL-1β and IL-18 by macrophages. Mechanistically, PKM2 translocates into the nucleus and combines with STAT3, enhancing its phosphorylation and recruitment to the NLRP3 promoter region, thereby increasing NLRP3 expression. This work defines PKM2 acts as an important nonmetabolic regulator of NLRP3 that modulates pyroptosis activation in macrophages and guides future therapeutic strategies development for ALF.

Ethnopharmacological relevance Traumatic brain injury (TBI) is a major cause of death and long-term disability in humans. Xuefu Zhuyu Decoction (XFZYD) has potential therapeutic effects on TBI, but its molecular mechanism involving non-coding RNAs (ncRNAs) remains unclear. Aim of the study To elucidate the mechanism of XFZYD, this study proposed an integrated ncRNA-based network pharmacology (ncRNP) strategy, combined with multi-omics analysis, in vivo and in vitro experiments. Unlike traditional network pharmacology which primarily focuses on protein-coding targets, the ncRNP strategy shifts the regulatory perspective to the transcriptional level, specifically targeting the herb-compound-ncRNA axis to bridge the gap between Traditional Chinese medicine (TCM) multi-component synergy and epigenetic regulation. Materials and methods The ncRNP framework was established through four integrated modules: 1) construction of herbal-ncRNA regulatory networks; 2) high-throughput miRNA profiling of TBI mice; 3) multi-omics integration to identify core “herb-miRNA-pathway” nodes; and 4) experimental validation. Male C57BL/6J TBI mice were treated with different doses of XFZYD, and their neurological functions were examined. The ncRNP integrative strategy was established and used in XFZYD. Electron microscopy, western blotting, qRT-PCR, and immunofluorescence were further performed to confirm the anti-autophagy effects of XFZYD by miR-323-3p. Results XFZYD treatment significantly improved neurological deficits and reduced neuronal loss and apoptosis. By implementing the ncRNP strategy which filters pharmacological targets through the lens of differential ncRNA expression, we identified a unique profile of 5 potential miRNAs. Through bioinformatics analysis and validation, miR-323-3p was selected as the key miRNA. We further confirmed that XFZYD normalized the pathological over-activation of autophagy after TBI by upregulating miR-323-3p, and subsequently suppressed the excessive activation of the AMPK/ULK1/Beclin-1 signaling axis. Overexpression of miR-323-3p directly inhibited the AMPK-dependent autophagy and restored cellular homeostasis. Conclusions XFZYD alleviates TBI-induced neuronal injury by rebalancing the miR-323-3p/AMPK-mediated autophagic flux. The established ncRNP strategy represents a methodological advancement over traditional network pharmacology by incorporating ncRNA-mediated epigenetic signatures, providing a more comprehensive and high-resolution framework for deciphering the complex pharmacological basis of TCM.

Background: Xuefu Zhuyu Decoction (XFZYD) is clinically applied to traumatic brain injury (TBI) based on its traditional function of activating blood circulation and eliminating stasis. However, its precise mechanism underlying its efficacy, particularly through epigenetic regulation, are poorly understood. Aim of the study: We hypothesized that the neuroprotective effects of XFZYD post-TBI are mediated through the modulation of transfer RNA-derived small RNAs (tsRNAs), a key class of epigenetic regulators. This study aimed to delineate the specific tsRNA-dependent molecular pathway underlying XFZYD's ability to mitigate neuroinflammation and facilitate neurological recovery. Materials and methods: We employed a murine TBI model treated with XFZYD. Following comprehensive assessment of neurological, histopathological, and inflammatory outcomes to test the mice behavior. The antiinfammatory roles of tRF-3-Leu-AAG was investigated in vivo and in vitro. RNA sequencing and bioinformatics analysis revealed G protein-coupled receptor 17 (Gpr17) is tRF-3-Leu-AAG's target. The direct interaction between tRF-3-Leu-AAG and Gpr17 is validated by dual-luciferase assay. Finally, in vitro rescue experiments conclusively established the tRF-3-Leu-AAG/Gpr17 axis as the functional pathway underlying XFZYD's effects. Results: XFZYD administration significantly attenuated neurological deficits, neuronal loss, and rescued cognitive impairment post-TBI. tRF-3-Leu-AAG, as a crucial mediator, which is suppressed by TBI and upregulated by XFZYD. The study demonstrated that tRF-3-Leu-AAG affect the inflammatory response. Critically, the antiinflammatory and neuroprotective effects of XFZYD were entirely dependent on tRF-3-Leu-AAG. We further delineated the downstream signaling by identifying Gpr17 as a direct and functional target of tRF-3-Leu-AAG. XFZYD mediated tRF-3-Leu-AAG binds to the 3 ' UTR of Gpr17 mRNA to suppress its expression, thereby inhibiting the Gpr17-induced pro-inflammatory pathway. Conclusion: This study elucidates that XFZYD exerts neuroprotection and anti-inflammation after TBI through tRF-3-Leu-AAG/Gpr17 axis. Our findings provide a modern scientific rationale for the application of XFZYD in treating TBI.

The global burden of lower respiratory infections (LRIs), upper respiratory infections (URIs), and otitis media attributable to air pollution has exhibited notable temporal patterns. Our study analyzed the patterns in disability-adjusted life years (DALYs) and age-standardized DALY rates (ASDRs) attributable to particulate matter pollution (PMP) for LRIs, and for URIs and otitis media (infants <1 year), using Global Burden of Disease (GBD) 1990-2021 estimates. We applied frontier analysis to estimate improvement potential by development status, assessed cross-country inequality, and used decomposition analysis to evaluate the contributions of population growth, aging, and epidemiological changes. Furthermore, an autoregressive integrated moving average (ARIMA) model was employed to forecast trends through 2031. Our findings revealed that the PMP -attributable burden of LRIs, infant URIs and infant otitis media, decreased globally from 1990 to 2021, with notable reductions in East Asia (LRIs, URIs), and Central Europe (otitis media). Despite progress, burdens remains highest in low-socio-demographic index (SDI) regions, indicating substantial potential for further reduction. Decomposition attributed most global declines to epidemiological change, whereas population growth increased burden in low-SDI regions. Projections suggest continued declines for PMP -attributable burden of LRIs and infant URIs but a slight rise for infant otitis media by 2031. These findings highlight the need for further targeted preventive interventions, especially in high-burden regions.

Purpose:Traumatic brain injury (TBI) triggers profound neuroinflammatory responses; however, the regulatory role of small nucleolar RNAs (snoRNAs) in TBI-associated neuroinflammation remains poorly understood. This study evaluated its prognostic value in TBI. Mice and Methods:A controlled cortical impact (CCI) model was established in male C57BL/6 mice and validated through modified neurological severity scoring (mNSS), hematoxylin-eosin (H&E) staining, and immunostaining for IgG leakage and Nissl substance. Cortical snoRNA expression profiles were assessed using microarray analysis, with differentially expressed candidates confirmed by quantitative real-time PCR (qRT-PCR). The spatial distribution of snoRNAs was determined via fluorescence in situ hybridization (FISH), while the anti-inflammatory effects of snoRNA Gm24418 were evaluated in vivo and vitro. Downstream molecular pathways were identified through transcriptomic sequencing combined with bioinformatics analysis. Results:Mice subjected to CCI exhibited significant motor and cognitive impairments (elevated mNSS), neuronal loss (as indicated by H&E and Nissl staining), and blood-brain barrier disruption (evidenced by IgG extravasation). Microarray analysis identified 47 dysregulated small nucleolar RNAs (snoRNAs), comprising 43 that were downregulated and 4 that were upregulated, with Gm24418 exhibiting the most significant downregulation. FISH confirmed the localization of Gm24418 predominantly in cortical neurons. Overexpression of Gm24418 in N2A cells and mice significantly reduced the levels of pro-inflammatory cytokines, including IL-1β, TNF-α, and IL-6, and suppressed the activation of Ccl2 and TNF signaling pathways. Mechanistic analyses indicated that Gm24418 overexpression is associated with downregulation of the TNF signaling pathway, thereby attenuating neuroinflammation and promoting the restoration of blood-brain barrier integrity following TBI. Conclusion:Gm24418 is identified as a neuron-specific snoRNA that ameliorates TBI-induced neuropathology through influencing the expression of key inflammatory mediators, including CCL2 and TNF-α, representing a promising novel therapeutic target for post-traumatic neuroinflammation.

BackgroundAcute liver failure (ALF) is a life-threatening syndrome characterized by rapid deterioration of liver function, resulting in high mortality and posing a substantial global health burden. Human embryonic stem cells (hESCs) possess unlimited self-renewal capacity and pluripotent differentiation potential. Transplantation of hESC-derived hepatocyte-like cells (HPLCs) represents a promising therapeutic strategy for ALF.MethodsA good manufacturing practice (GMP)-compliant differentiation process was developed to generate HPLCs from hESCs, and their biological characteristics and functional properties were systematically evaluated. A comprehensive series of preclinical safety and efficacy studies was performed, including dose-escalation experiments, biodistribution analysis, comparative evaluation of administration routes, and carcinogenicity testing. The therapeutic efficacy and safety of HPLCs were assessed in a fatal rat model of D-galactosamine (D-gal) and lipopolysaccharide (LPS)-induced ALF. In addition, the HPLCs underwent quality evaluation by the National Institutes for Food and Drug Control (NIFDC), and an independent safety assessment was conducted.ResultsA high-efficiency system was established for the generation of qualified, clinical-grade HPLCs from hESCs under GMP-compliant conditions. The HPLCs exhibited multiple mature hepatocyte functions, including carbohydrate and lipid metabolism, hepatic synthetic and storage functions, inducible cytochrome P450 activity, albumin secretion, and urea production. The HPLCs met the certification standards of the NIFDC of China. Transplantation of HPLCs significantly improved survival in ALF rats, with survival rates of 72.4% following tail vein injection and 66.7% following intraperitoneal injection, compared with 6.67% in the control group. HPLC transplantation also promoted recovery of liver function, as reflected by improvements in biochemical and coagulation parameters. Preclinical safety evaluations confirmed the biosafety of HPLCs, with no evidence of acute toxicity or tumorigenicity. A Phase I clinical trial (ChiCTR2100052988) for the treatment of ALF and acute-on-chronic liver failure (ACLF) has been approved by the National Health Commission of the People's Republic of China (Filing Number: MR-43-21-014643) and has been initiated.ConclusionsA novel multistage, GMP-compliant process was developed for the effective and reproducible differentiation of hESCs into hepatocytes. The resulting HPLCs demonstrated robust hepatocyte functions, therapeutic efficacy in an ALF animal model, and favorable biosafety profiles. These findings support the clinical translation of HPLCs, with an ongoing Phase I clinical trial designed to evaluate their safety and feasibility in patients with ALF and ACLF.

Chronic stress and sympathetic signaling, mediated by the β2-adrenergic receptor (ADRB2), are implicated in cancer progression. In melanoma, a neural crest-derived malignancy, the interplay between neuroendocrine signals and tumor cell plasticity remains poorly understood. Elucidating how ADRB2 activation translates into pro-tumorigenic transcriptional programs is crucial for developing novel therapeutics. We combined genetic and pharmacological ADRB2 modulation in melanoma models with transcriptomics, mechanistic assays, and patient sample analysis. ADRB2 inhibition suppressed tumor growth by arresting the cell cycle and inducing apoptosis. Transcriptomic analysis revealed MAGEA1 as the most downregulated gene upon ADRB2 knockout. Mechanistically, ADRB2 signaling via the PKA pathway upregulated and promoted the nuclear translocation of the transcription factor SOX10. SOX10, in turn, directly bound to the MAGEA1 promoter to drive its transcription. In clinical specimens, high expression of ADRB2, SOX10, and MAGEA1 correlated with poorer patient prognosis. Our study defines a novel ADRB2-PKA-SOX10-MAGEA1 signaling axis that critically promotes melanoma growth. This axis positions ADRB2 as a key node linking neuroendocrine stress signals to the core transcriptional machinery governing melanoma cell proliferation and survival. Targeting ADRB2 presents a promising therapeutic strategy to counteract stress-induced melanoma progression.

Perioperative stress hyperglycemia is a transient but frequent metabolic disturbance strongly linked to postoperative organ injury and mortality; however, the immunometabolic mechanisms driving this association remain largely undefined. In a two-center cohort of patients undergoing total aortic arch replacement, we identify stress hyperglycemia as an independent determinant of poor postoperative outcomes that associates strongly with CD4+ T cell loss. Hyperglycemia induces inflammatory PANoptosis in CD4+ T cells from patients in response to surgical trauma. This results from elevated glucose driving the accumulation and release of succinate from monocytes, which subsequently acts on CD4+ T cells to compromise mitochondrial integrity and activate ZBP1-mediated PANoptosis. Our findings define a monocyte-T cell metabolic signaling axis that transduces hyperglycemic stress via elevated succinate to adaptive immune cell death and reveal potential therapeutic targets to prevent postoperative immune dysfunction and organ injury, especially for patients with hyperglycemic comorbidities.

[This corrects the article DOI: 10.3389/fpubh.2026.1666976.].

Inflammatory bowel disease (IBD) remains a major global health burden, driven by a multifaceted pathogenesis that includes immune dysregulation, epithelial barrier disruption, oxidative stress, and gut microbiota imbalance. Addressing these interconnected processes requires multi-targeted therapeutic strategies that go beyond conventional single-pathway interventions. Baicalein, a key flavonoid derived from Scutellaria baicalensis (Huang Qin), has emerged as a promising candidate due to its broad-spectrum pharmacological properties. This review synthesizes current advances in understanding how baicalein exerts therapeutic effects against IBD through an integrated network of mechanisms. These include potent suppression of inflammatory signaling and oxidative stress, restoration of epithelial integrity via modulation of tight junction proteins and the MLCK/p-MLC2 pathway, and reprogramming of dysregulated immune circuits by rebalancing T-cell subsets and macrophage polarization. In addition, baicalein mitigates pathological cell death pathways such as ferroptosis and pyroptosis and orchestrates beneficial shifts in the gut microbiota–metabolite axis. By bridging classical anti-inflammatory mechanisms with emerging immunoregulatory and microbiome-targeted insights, this review highlights baicalein as a potential multi-dimensional therapeutic strategy for IBD and outlines future directions for its clinical translation.

Approximately 5-10% of all cancer types are hereditary cancer syndromes, which are caused by pathogenic mutations in cancer susceptibility genes. In this investigation, a hereditary cancer pedigree was collected from a province in southern China, and the proband was a 31-year-old woman with breast cancer. Utilizing blood whole exome sequencing technology and bioinformatics analysis, the sole heterozygous missense mutation in PIBF1 that exhibits trait segregation was identified: PIBF1 (p.R405Q). The pedigree also included two other mutations that may be linked to carcinogenesis: RAD51D (p.K91Ifs*13) and BRCA2 (p.G3134Afs*29). This research concentrated on PIBF1 (p.R405Q) and employed breast cancer as a tumor model. In vitro and in vivo experiments showed that PIBF1-WT suppressed breast cancer cell proliferation, colony formation, invasive ability, and tumorigenesis. However, PIBF1 (p.R405Q) attenuated or inhibited the function of PIBF1-WT. Mechanistically, PIBF1-WT resisted cisplatin-induced DNA damage, significantly down-regulated the expression of γ-H2AX, and affected DNA damage repair, thus exerting a cancer inhibitory function. Interestingly, PIBF1 (p.R405Q) affects protein stability, thereby mitigating or eliminating the inhibitory effect of PIBF1. Furthermore, this family's polygenic risk factors for cancer are analyzed, and there is speculation about potential synergistic effects between PIBF1 and DNA damage repair genes like BRCA2 and RAD51D. In conclusion, PIBF1 regulates the cell cycle and DNA damage repair, PIBF1(p.R405Q) increases susceptibility to cancer, multiple DNA damage repair gene mutations may synergistically promote cancer progression in this cancer family lineage, and PIBF1(p.R405Q) may be one of the polygenic risk factors for familial hereditary cancer syndromes.

Acquired brain injury (ABI), an injury resulting from a direct lesion of the brain, encompasses a spectrum of conditions, including traumatic brain injury, cerebral hemorrhage, cerebral ischemia, brain tumor, etc. Clinical interventions for these diseases remain limited. Intervention for the primary injury is still lacking, while the secondary damage holds potential for improvement. Ferroptosis has emerged as a significant contributor to the secondary injury. Recent investigations have progressively unraveled the mechanistic underpinnings of ferroptosis in ABI. Natural compounds have recently exhibited promising therapeutic potential in ABI by effectively mitigating brain damage associated with dysregulated iron metabolism. Therefore, this comprehensive review elucidates the therapeutic potential of natural compounds in treating ABI and their regulatory mechanisms involving ferroptosis. These findings provide valuable insights for guiding clinical interventions and hold promise for improving the prognosis of patients with ABI.