Lulu Wang

Cisplatin-induced acute kidney injury (AKI) remains a serious clinical complication, with excessive reactive oxygen species (ROS) recognized as key contributors. The natural antioxidant epigallocatechin-3-gallate (EGCG) shows promise in mitigating oxidative stress–related damage. However, its clinical application is limited by poor stability and low renal bioavailability. To address this, we developed a biocompatible nanoplatform by encapsulating EGCG within mesoporous polydopamine nanoparticles (EGCG-MPDA). Ultrasmall nanoparticles (<10 nm or <20 kDa) undergo rapid glomerular filtration and renal clearance, limiting therapeutic retention. While uncoated MPDA nanoparticles (∼200 nm) are large enough to avoid renal filtration, their size renders them highly susceptible to opsonization and MPS sequestration. To address this MPS-mediated clearance, we coated MPDA with a preclinically used BSA shell to create EGCG-MPDA@BSA. The biocompatible BSA corona acts as a “stealth” layer to attenuate opsonization, reduce early hepatic sequestration, and enhance interactions with peritubular endothelial cells, promoting nanoparticle passage into injured tubular epithelial cells. In a murine cisplatin-induced AKI model, EGCG-MPDA@BSA exhibited significantly enhanced therapeutic efficacy compared to uncoated nanoparticles and free EGCG. Transcriptomic and biochemical analyses revealed that its superior therapeutic efficacy arises from the activation of the Nrf2/HO-1/GPX4 antioxidant pathway, thereby alleviating oxidative stress, inflammation, and tubular damage. Collectively, this work presents an albumin corona strategy that enables effective renal retention of large nanoparticles, offering a safe, translatable approach for localized AKI therapy.

Mitochondrial function plays a critical role in skin aging. Chlorogenic acid (CGA), a botanical compound, has demonstrated regulatory effects on mitochondrial function and senescence inhibition. However, whether the anti-aging effects of CGA are attributable to its regulation of mitochondrial function remains unclear. There is a need to investigate the anti-aging effect and mechanism of CGA by modulating mitochondrial function, particularly its mode of action on mitochondrial function. Normal human dermal fibroblasts and human epidermal keratinocytes were used to detect the regulation of collagen I production, mitochondrial functions, and anti-aging properties of CGA and confirmed by mitochondrial transplantation. The photo-aging mouse model was established by ultraviolet (UV) radiation, followed by the treatment of CGA-gel (1 mmol/kg/d) for 14 days. The skin tissues were collected and tested. CGA promotes collagen I (Col1) production by activating the TGF-β/Smad signaling pathway, while concurrently inhibiting cellular senescence. CGA administration significantly reduced the expression of p21, senescence-associated secretory phenotype (SASP) production, and SA-β-Gal activity in skin cells. Additionally, CGA treatment notably enhanced mitochondrial function, improving disrupted mitochondrial cristae in senescent cells and boosting the oxidative phosphorylation (OXPHOS) process. ATP levels increased by approximately 40-80% following CGA treatment. Mitochondrial transplantation further confirmed CGA's anti-aging effects are linked to mitochondrial function. CGA significantly mitigated UV-induced reduction in Col1, suppressed p21 expression and SASP production, and improved mitochondrial morphology and structure in vivo. CGA promotes Col1 production and attenuates skin cellular senescence, with these effects being directly associated with mitochondrial regulation. Thus, CGA holds promise as a potent agent for preventing cellular senescence.

In triple-negative breast cancer (TNBC), chemotherapy-induced immunogenic cell death (ICD) often fails to trigger truly effective antitumor immunity. This failure primarily stems from the simultaneous release of damage-associated molecular patterns (DAMPs) and immunosuppressive prostaglandin E2 (PGE₂), creating an intrinsic NOT-AND signaling conflict. This barrier hinders efficient immune priming, a response rarely induced by conventional chemotherapy. To address this conflict while minimizing toxicity, R-Gem@Cel-PV, a spatiotemporally programmed nanovesicle, was designed to impose both spatial localization and sequential signal control within the tumor microenvironment. Following preferential accumulation in tumor tissue, enzymatic disassembly of the nanomedicine triggers the rapid release of celecoxib to suppress local PGE₂ signaling and alleviate immune suppression. Subsequently, the delayed activation of a phospholipid-gemcitabine prodrug induces DAMP-releasing cell death. This temporal decoupling—unachievable with free drug combinations—converts gemcitabine from a weak ICD inducer into a potent one. In TNBC models, R-Gem@Cel-PV boosted dendritic cell maturation, orchestrated a robust antitumor immune response, and significantly inhibited both primary tumor growth and metastasis. These findings demonstrate that resolving the immunosignal conflict through precise spatiotemporal control is essential for effective immune engagement in TNBC and offer a generalizable strategy for reprogramming the immune response to chemotherapy in immune-refractory tumors.

Asthma is a chronic inflammatory disease with limited therapeutic options, highlighting the urgent need to explore alternative mechanisms and agents. Chlorogenic acid (CGA), a dietary polyphenol, exhibits anti-asthmatic properties, but its precise molecular mechanisms remain poorly understood. This study aimed to elucidate the mechanistic basis of CGA’s anti-asthmatic effects, hypothesizing a central role in regulating polyunsaturated fatty acid metabolism and ferroptosis. An ovalbumin-induced murine asthma model was established in female BALB/c mice to evaluate the therapeutic efficacy of CGA through inflammatory cell counts, cytokine levels (ELISA), and lung histopathology. Integrated lung lipidomics (LC-MS/MS) was employed to profile lipid mediators and phospholipids. The underlying mechanism was investigated in erastin-induced ferroptosis in BEAS-2B cells and validated in mouse lung tissue using qPCR, immunofluorescence, and assays for reactive oxygen species (ROS) and Fe²⁺. CGA treatment significantly attenuated airway inflammation, reduced Th2 cytokine (IL-4, IL-5) and IgE levels, and ameliorated lung pathology in a dose-dependent manner. Lipidomics revealed that asthma was associated with dysregulated docosahexaenoic acid (DHA) metabolism, characterized by elevated pro-inflammatory lipid peroxidation products (e.g., 11-HDoHE, 14-HDoHE), a profile reversed by CGA intervention. Mechanistically, molecular docking and subsequent validation identified CGA as an activator of the Nrf2 antioxidant pathway, leading to upregulation of the key ferroptosis defense genes SLC7A11 and GPX4 both in vitro and in vivo. Consequently, CGA treatment suppressed erastin-induced ROS production and Fe²⁺ accumulation in BEAS-2B cells. In conclusion, this study demonstrates that CGA exerts anti-asthmatic effects by reprogramming DHA metabolism to suppress ferroptosis while enhancing antioxidant pathways. These findings reveal a novel mechanistic axis for CGA and establish that targeting lipid peroxidation-driven ferroptosis represents a promising therapeutic strategy for asthma.

Background: Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism, and if untreated, leads to severe neurocognitive impairment. Over the past 2 decades, treatment strategies have evolved from strict dietary phenylalanine restriction to include pharmacological therapies such as tetrahydrobiopterin and, more recently, enzyme substitution with pegvaliase. Despite these advances, significant heterogeneity exists in global research priorities, collaboration patterns, and the translation of emerging therapies into clinical practice. A systematic overview of the field’s development, thematic shifts, and remaining knowledge gaps is currently lacking. Objective: This study aimed to provide a systematic bibliometric analysis of global treatment research on PKU from 2000 to 2025. The aim was to quantify publication trends, collaboration patterns, thematic evolution, and research gaps, thereby informing future scientific and clinical directions. Methods: A search of the Web of Science Core Collection was performed on September 13, 2025. The search initially identified 1877 records. After screening, 1462 English-language articles and reviews were included. Publication trends were analyzed using Microsoft Excel (version 16.101), while VOSviewer 1.6.20 and CiteSpace 6.4R1 were used to visualize country- and institutional-level collaborations, journal networks, keyword co-occurrence, citation bursts, and thematic clusters. Statistical charts were generated with GraphPad Prism 10.2.1. Results: Annual publication output demonstrated an overall upward trend, peaking in 2022 with 111 publications. The United States led in both publication volume (375 studies) and total citations (11,142 citations), maintaining strong collaborative ties with several European countries, particularly the Netherlands and the United Kingdom. China ranked seventh globally in publication volume, although its citation impact remains comparatively limited. Key institutions, including the University of Groningen and Birmingham Children’s Hospital, as well as prominent scholars such as Francjan J van Spronsen and Anita MacDonald, have occupied central positions in the global PKU treatment research collaboration network over the study period. High-frequency and high-centrality keywords, such as “phenylalanine,” “dietary treatment,” and “tetrahydrobiopterin,” highlighted continued emphasis on metabolic control and targeted therapies. Keyword burst analysis revealed a gradual shift from conventional dietary management toward enzyme replacement therapies, investigations of neurocognitive outcomes, and precision medicine–oriented approaches. Conclusions: Over the past 25 years, PKU treatment research has progressed from foundational dietary interventions to molecular mechanistic studies and individualized therapeutic strategies. Future research should prioritize longitudinal multiomics investigations, targeted metabolic correction technologies, gene-based therapeutic approaches, and enhanced international collaboration, particularly to strengthen diagnosis and management capacities in low- and middle-income regions. Such efforts will be critical to advancing global standards of PKU care.

Berberine (BBR), a protoberberine alkaloid with a long history of medicinal use, has consistently demonstrated benefits in glucose–lipid metabolism and inflammatory balance across both preclinical and human studies. These diverse effects are not mediated by a single molecular target but by BBR’s capacity to restore network coordination among metabolic, immune, and microbial systems. At the core of this regulation is an AMP-activated Protein Kinase (AMPK)-centered mechanistic hub, integrating signals from insulin and nutrient sensing, Sirtuin 1/3 (SIRT1/3)-mediated mitochondrial adaptation, and inflammatory pathways such as nuclear Factor Kappa-light-chain-enhancer of Activated B cells (NF-κB) and NOD-, LRR- and Pyrin Domain-containing Protein 3 (NLRP3). This hub is dynamically regulated by system-level inputs from the gut, mitochondria, and epigenome, which in turn strengthen intestinal barrier function, reshape microbial and bile-acid metabolites, improve redox balance, and potentially reverse the epigenetic imprint of metabolic stress. These interactions propagate through multi-organ axes, linking the gut, liver, adipose, and vascular systems, thus aligning local metabolic adjustments with systemic homeostasis. Within this framework, BBR functions as a negentropic modulator, reducing metabolic entropy by fostering a coordinated balance among these interconnected systems, thereby restoring physiological order. Combination strategies, such as pairing BBR with metformin, Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, and agents targeting the microbiome or inflammation, have shown enhanced efficacy and substantial translational potential. Berberine ursodeoxycholate (HTD1801), an ionic-salt derivative of BBR currently in Phase III trials and directly compared with dapagliflozin, exemplifies the therapeutic promise of such approaches. Within the hub–axis paradigm, BBR emerges as a systems-level modulator that recouples energy, immune, and microbial circuits to drive multi-organ remodeling.

Radiotherapy for abdominal malignancies is limited by intestinal toxicity and secondary colorectal cancers. Here, we develop an oral, microbiota-responsive nano-amifostine (CS/PEC-AMF NPs) system that achieves site-specific radioprotection in the colorectum without compromising antitumor efficacy. By conjugating amifostine to pectin and encapsulating it with chitosan, the nanoparticles enable pH- and microbiota-triggered release in the large bowel, safeguarding drug bioactivity during gastrointestinal transit. In murine models, CS/PEC-AMF NPs attenuate both acute and chronic radiation-induced bowel injury, restore epithelial integrity, preserve stem cell populations, and promote tight junction repair. Integrated metagenomic and metabolomic analyses reveal that the system normalizes gut microbiota diversity and composition, increases short-chain fatty acid production, and facilitates macrophage polarization towards the anti-inflammatory M2 phenotype. Notably, the formulation synergistically enhances tumor suppression and extends survival in orthotopic colorectal tumor models undergoing radiotherapy and reduces the incidence of secondary colorectal tumors post-irradiation. Mechanistically, transcriptomic analysis demonstrates the suppression of proinflammatory pathways and the promotion of DNA repair programs. This study provides a paradigm for leveraging functional nanomaterials to orchestrate precise, tissue-specific radioprotection and immune modulation, addressing a key challenge in abdominal cancer therapy. Graphical abstract

Metabolic dysfunction‐associated steatotic liver disease (MASLD) is a multifactorial chronic liver disorder driven by an ensemble of interrelated pathological processes, including insulin resistance, lipid accumulation, oxidative stress, immune dysregulation, gut microbiota imbalance, and hepatocyte injury‐induced cell death. These overlapping mechanisms pose significant challenges for effective treatment, as conventional single‐target therapies often fail to address the systemic complexity of the disease. Recent advances in functional nanomedicine have introduced promising avenues for MASLD intervention by enabling the development of nanoplatforms specifically engineered to interact with disease‐specific pathophysiological features. These systems incorporate stimuli‐responsive drug release, targeted hepatic accumulation, and intrinsic therapeutic activity, allowing for simultaneous modulation of multiple pathological pathways. This review presents a pathophysiology‐informed framework for nanomedicine design in MASLD therapy. How diverse platforms are strategically tailored to regulate reactive oxygen species (ROS) production, modulate immune imbalance, restore insulin signaling, inhibit ferroptosis, and rebalance gut microbial dysbiosis is examined. Moreover, emerging approaches such as carrier‐free, self‐assembling systems and multifunctional yet intentionally minimalist architectures that enhance translational potential are highlighted. Together, these strategies exemplify a shift toward mechanism‐driven, entropy‐informed nanotherapeutics, wherein negentropy‐oriented and leading‐axis design principles offer a promising roadmap for restoring metabolic homeostasis in complex disease contexts such as MASLD.

Liver fibrosis, a progressive condition with limited pharmacotherapies, poses a global health challenge. Scutellarin (SCU), a flavonoid derived from Erigeron breviscapus, has demonstrated anti-fibrotic activity and modulates gut microbiota. Emerging evidence suggests that SCU may also influence the hepatic microbiome. However, its clinical utility is constrained by poor water solubility and low oral bioavailability. Here, we developed an SCU-loaded nanoemulsion (SCE) to enhance solubility and liver-targeted delivery. In vitro, SCE increased SCU uptake in hepatic stellate cells (HSCs) and significantly inhibited TGF-β1-induced fibrogenesis. In a bile duct ligation (BDL) mouse model, oral administration of SCE improved hepatic SCU accumulation and produced superior anti-fibrotic efficacy. SCE treatment attenuated fibrosis and collagen deposition in the liver and improved liver function markers. Mechanistic investigations using 16S rRNA sequencing revealed that SCU treatment was associated with beneficial microbiota changes, although its main therapeutic effects were achieved through enhanced hepatic targeting. Notably, the SCE formulation was well-tolerated, showing no significant toxicity in vitro or in vivo. In conclusion, the SCU-loaded nanoemulsion achieved enhanced hepatic delivery of SCU and exerted potent anti-fibrotic effects via multiple mechanisms, including direct suppression of fibrogenesis and ancillary modulation of the gut–liver microbiome, offering a promising therapeutic strategy for liver fibrosis.