Scientific Reports
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2025
·Vol. 15
·期 1
·1-13
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IF 3.9
Wu Dan,Niu Jingjie,Hu Jianping,Wang Hao,Kuang Haixue
This study aimed to assess the anti-hyperuricemia efficacy of Zhejiang psyllium polysaccharides (ZPP) in rats and to explore its underlying mechanism. Hyperuricemia was induced by intragastric administration of potassium oxonate, hypoxanthine, and adenine. The serum levels of uric acid (UA), creatinine (Cr), and blood urea nitrogen (BUN) were measured, and kidney pathology was examined. Serum metabolomics was employed to monitor metabolic alterations following ZPP intervention. Metagenomic analysis was conducted to investigate the impact of ZPP on the intestinal flora of hyperuricemia rats. The results showed that ZPP could significantly reduce the serum UA level in hyperuricemia rats and exhibited a certain renal protective effect. The metabolomics results indicated that ZPP regulates uric acid levels in rats with hyperuricemia and ameliorates renal pathological changes by modulating biomarkers associated with purine metabolism, amino acid metabolism, and lipid metabolism. Metagenomic research also found that ZPP could increase the relative abundance of uric acid metabolism-related probiotics, such as Limosilactobacillus reuteri and Lactobacillus murinus , thereby improving intestinal flora imbalance in rats with hyperuricemia.
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MOLECULES
·
2025
·Vol. 30
·期 14
·2940
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IF 4.6
Liang Chen,Qiao Wu,Chen Yang,Xiulan Xin,Zhaochu Xu,Shuai Luo,Hao Liang
Natural products possess potent pharmacological activities and health benefits. However, drawbacks such as water insolubility, poor stability, and low bioavailability limit their practical applications. This research is dedicated to the development of suitable natural self-assembled nano-delivery systems to encapsulate natural molecule drugs, improving their dispersion and stability in aqueous solution. As a model drug, curcumin (Cur) was encapsulated in zinc–adenine nanoparticles (Zn–Adenine), based on the self-assembly of a coordination matrix material. Hyaluronic acid (HA) was further functionalized on the surface of Cur@(Zn–Adenine) to realize a tumor-targeted delivery system. The morphology was characterized through TEM and zeta potential analyses, while the encapsulation mechanism of the nanoparticles was researched via XRD and FTIR. The formed Cur@(Zn–Adenine)@HA nanoparticles exhibited good drug loading efficiency and drug loading rate. Moreover, compared to free Cur, Cur-loaded (Zn–Adenine)@HA showed enhanced pH stability and thermal stability. In particular, Cur@(Zn–Adenine)@HA demonstrated excellent biocompatibility and strong specificity for targeting CD44 protein on cancer cells. The above results indicate that (Zn–Adenine)@HA NPs can serve as an effective nano-delivery system for hydrophobic substances.
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MOLECULAR PHARMACEUTICS
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2025
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IF 4.5
Liang Zhang,Ting Wang,Yunyi Shan,Weijie Zhang,Jing Yao,Hui Xiong
Triple-negative breast cancer (TNBC) is a highly aggressive subtype with limited therapeutic options due to its resistance to conventional targeted therapies. TNBC cells heavily rely on oxidative phosphorylation (OXPHOS), making mitochondrial electron transport chain (ETC) inhibition a promising therapeutic approach. However, existing ETC inhibitors pose severe cytotoxicity risks, highlighting the need for biocompatible alternatives. In this study, we develop an MgO-ICG suspension (MgO-ICG@S), utilizing magnesium oxide (MgO), biocompatible pharmaceutical excipients that are already in widespread use as both an ETC-blocking agent and a drug carrier for the photosensitizer indocyanine green (ICG). This approach enables a bidirectional ETC blockade by disrupting ETC electronic transmission and functionality while inducing a unique mitochondria-targeted drug delivery effect. Additionally, laser irradiation activates ICG, generating reactive oxygen species (ROS) that further sensitize tumor cells to ETC inhibition. The combination of ETC blockade and photodynamic therapy (PDT) creates a synergistic cycle of oxidative damage, amplifying antitumor effects and significantly improving therapeutic outcomes. This study offers a promising strategy for effective, targeted TNBC treatment and provides valuable insights into the development of biocompatible ETC-blocking agents for clinical applications.
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Regenerative Biomaterials
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2025
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IF 8.1
Han Yuemei,Wang Jiahao,Chen Hao,Lin Quankui
Intraocular lens (IOL) is a crucial implant for cataract therapy. Posterior capsule opacification (PCO) is the most common postoperative complication after IOL implantation, which is the abnormal hyperplasia of the residual lens epithelial cells (LECS) after IOL implantation in cataract surgery. It is reported that the cellular microenvironment in the lens capsule changes after surgery, such as the elevated secretion of Matrix metalloproteinases (MMPs) and a decrease in pH due to undesired cell proliferation. In this study, MMP-2 and pH-triggered drug delivery polysaccharide multilayer coating was designed and introduced onto the IOL surface for obtaining the cellular microenvironment-sensitive drug-eluting intraocular implant. The methacrylated heparin (HEP-MA) was synthesized and used to layer-by-layer self-assemble with the doxorubicin-loaded chitosan nanoparticles on the IOL surface. The Matrix metalloproteinase-2 (MMP-2) sensitive peptide with Cysteine contained in both ends (GCRD-GPQGIWGQ-DRCG) was then used to crosslink the polysaccharide multilayer via the Michael addition reaction between sulfhydryl group in Cysteines and double bonds in methacrylate groups. The multilayer construction and subsequent cross-linking were validated through Ultraviolet-visible spectrophotometer (UV-Vis) and Fourier-transform infrared spectroscopy (FTIR). After modification, the IOL material surface becomes more hydrophilic while the optical properties were well maintained. The MMP-2 and pH-sensitive drug sustained release coating were successfully obtained on the IOL surface via such design. The enzyme-triggered cell proliferation inhibition was realized in the in vitro experiments. In an animal model, significant upregulation of MMP-2 was observed in the aqueous humor after cataract surgery. The multi-functionalized polysaccharide-coated IOL implanted in the animal eye via cataract surgery effectively inhibits PCO formation while it keeps good in-vivo biosafety.
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Hepatobiliary & Pancreatic Diseases International
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2025
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IF 4.4
Han-Ying Zhou,Ting Li,Yuan-Qiang Lu
Background Diquat, a commonly employed bipyridyl herbicide, is recognized for its hepatotoxic effects attributed to the generation of reactive oxygen species. Baicalin (BAI), a flavonoid derivative, has garnered significant research interest for its hepatoprotective properties. Nevertheless, the clinical application of BAI is constrained by its limited water solubility and poor bioavailability. To address these challenges, BAI-nanoliposome (BAI-NL) has emerged as a novel drug delivery platform aimed at enhancing therapeutic outcomes. Methods We used diquat-induced liver injury mouse model and AML12 hepatocytes to test the protective effect of BAI and BAI-NL on liver inflammation, oxidative stress, and mitochondrial function. The parameters included histological, biochemical, and molecular biological analyses. Results In the diquat-induced model, both BAI and BAI-NL exhibited effectiveness on attenuating liver inflammation. Ex vivo analyses further indicated that BAI-NL was superior to BAI in preserving mitochondrial membrane potential, reducing oxidative stress, and modulating the phosphatase and tensin homolog-induced putative kinase 1 (PINK1)/Parkin RBR E3 ubiquitin-protein ligase (Parkin) signaling pathway. These findings enhanced mitophagy and facilitated the removal of damaged mitochondria. Conclusions BAI-NL exhibited superior hepatoprotective effects compared to free BAI, possibly by reducing inflammation, preserving mitochondrial homeostasis, and reinstating autophagic balance through modulation of the PINK1/Parkin signaling pathway. These outcomes indicate a groundbreaking method for addressing liver diseases and underscore the potential of nanoliposome technology in augmenting the efficacy of natural compounds.
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POULTRY SCIENCE
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2025
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IF 4.2
Elham Ghashghaei,Minghui Wang,Ahmed Mijiyawa,Hai Lin
Amino acids in the brain modulate eating behavior and energy balance. The aim of the present study was to investigate the effects of DL-methionine (DL-Met), L-lysine monohydrochloride (L-Lys-HCl), and taurine (Tau) on feed intake and the mRNA expression levels of appetite-related hypothalamic neuropeptides in chicks. DL-Met, L-Lys-HCl, or Tau was intracerebroventricularly (ICV) administered to 5-day-old layer-type chicks, and the feed intake was recorded until 1 h post-injection. Quantitative PCR was performed to determine the hypothalamic mRNA expression levels of neuropeptide Y ( NPY ) and its receptors, agouti-related protein ( AgRP ), pro-opiomelanocortin ( POMC ), cocaine- and amphetamine-regulated transcript ( CART ), and melanocortin receptors. Our results indicated that injection time and treatment have a significant effect on food intake. Food intake decreased significantly at 30 and 60 minutes after ICV administration of DL-Met (1.678 μmol), L-Lys-HCl (6.856 μmol), and Tau (5.006 μmol) compared to the control group ( P > 0.05). On the contrary, a high dose of each amino acid did not alter feed intake ( P > 0.05). The result showed that ICV injection of DL-Met (1.678 μmol) significantly decreased the mRNA expressions of NPY , NPY4R , and NPY6R ( P < 0.05), but had no significant effect on the mRNA expressions of NPY1R, NPY5R, and AgRP in the hypothalamus ( P > 0.05). Similarly, ICV injection of L-Lys-HCl (6.856 μmol) and Tau (5.006 μmol) significantly decreased mRNA levels of NPY, NPY4R, and NPY6R ( P < 0.05), without affecting the mRNA expressions of NPY1R, NPY5R, and AgRP ( P > 0.05). DL-Met had no effect on anorexigenic gene expression ( P > 0.05). L-Lys-HCl upregulated MC1R ( P < 0.05), and Tau upregulated POMC and MC3R ( P < 0.05), and both had no influence on CART, MC4R , or MC5R ( P > 0.05). The result suggests that both orexigenic and anorexigenic neuropeptide genes are involved in the effects of DL-Met, L-Lys-HCl, and Tau. The effect of DL-Met, L-Lys-HCl, and Tau acts in a dose-dependent manner in the hypothalamus to influence feed intake.
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Cell Reports
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2025
·
IF 6.9
Sijia Xiang,Zhuanghao Hou,Yu Wang,Yang Yang,Hongze Hu,Chang Yin,Guangming Huang,Kaiming Cao,Yangzhong Liu
Liquid-liquid phase separation (LLPS) of biomolecules is a crucial mechanism in regulating cellular functions through dynamic formation of membrane-less organelles. The assembly of nucleation seeds is a key step that triggers LLPS; however, it is challenging to precisely study its assembly mechanism due to the complexity of the condensation process. Recently, metal ions have been found to play important roles in inducing LLPS. To elucidate the assembling mechanism, a small ubiquitin-like modifier (SUMO) protein was employed as a model protein to study metal-induced condensation. The results indicate that SUMO possesses two weak Cu(II)-binding sites across the protein surface, enabling intermolecular bridging among SUMO molecules. The formation of assembling seeds is confirmed by mass photometry analysis, showing the Cu(II)-induced dynamic clusterization of SUMO at nanoscale. Increasing the Cu(II) binding affinity of SUMO significantly promotes the protein condensation, underscoring the pivotal role of Cu(II) coordination in LLPS. This work provides insights into the protein assembly mechanism through non-specific intermolecular metal coordination.
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Biomaterials Advances
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2025
·
IF 6
Meng Lan,Fansu Meng,Lanwen Gao,Anil K. Giri,Makiya Nishikawa,Kosuke Kusamori,Jaiwoo Lee,Mulazim Hussain Asim,Shumaila Arshad,Honghui Gu,Qi Li,Lina Yang,Zhong Chen,Zhenjiang Yang,Jiajia Qin,Yu Cai
Background Triple-negative breast cancer (TNBC) faces great challenges in clinical treatment, owing to the lack of specific therapeutic targets and easy metastasis. The natural component baicalin can effectively inhibit the growth and metastasis of TNBC; however, it has some limitations, such as poor targeting and side effects. Nano targeted delivery systems can improve drug efficacy by enhancing drug accumulation and controlling drug release. Objective Trop-2 transmembrane glycoprotein expression is high in TNBC cells, suggesting that it can serve as a specific active targeting molecular-modified nano drug delivery system for TNBC to overcome non-specific distribution. Based on the characteristics of high-concentration glutathione in the tumor microenvironment, redox-sensitive nano-prodrugs (Trop2-BA-ss-PPEP) have been designed to achieve intelligent slow control and release of drugs. Methods The chemical structure of the Trop2-BA-ss-PPEP, and its stability, reductive response to drug release behavior, and targeting ability in vitro were characterized. Cell experiments and a transplanted tumor model verified the anti-tumor effect and biosafety. Results Trop2-BA-ss-PPEP was stable in a physiological environment and rapidly released the drug under reducing conditions. The experiments showed that Trop2-BA-ss-PPEP significantly promoted cellular uptake, and drug accumulation and maintenance time at the tumor site were increased. It enhanced the inhibitory effect on metastasis in vivo and in vitro, and no obvious toxicity or side effects were observed. Conclusion Trop2-BA-ss-PPEP was successfully constructed. The targeting ability, microenvironment responsiveness, and anti-tumor metastatic effects of Trop2-BA-ss-PPEP provide a new strategy for TNBC therapy, which has good application and transformation potential.
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International Journal of Pharmaceutics-X
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2025
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IF 6.4
Yuhua Tong,Sijie Zhou,Yongjie Guo,Xiaoli Jin,Meiting Yu,Chunyun Feng,Hao Chen,Xingjie Zan,Jinyang Li
The specificity and low toxicity of protein drugs are significant for disease treatment but are strongly limited by their weak tissue penetrative capacity. Although formulating proteins with nanoparticle is an alternative strategy, the low encapsulation efficiency (EE) and loading capacity (LC) of protein drugs and their potential for protein inactivation remain significant challenges. Herein, the de novo designed peptide (Arg-His-Cys-Arg-His-Cys-Arg-His-Cys) (RHC) 3 , zinc ions (Zn 2+ ), and the anti-neovascular protein drug Bevacizumab (Beva) were co-assembled to form PZA@Beva (peptide and Zn 2+ assemblies encaspsulated Beva) nanomedicine, aiming to overcome the challenges associated with corneal neovascularization (CNV) model. The optimized size of PZA@Beva is approximately 162.5 nm, with EE% and LC% of Beva 92.7 % and 55.8 %, respectively. The bioactivity of encapsulated Beva was preserved, protecting it from proteolytic degradation, and the release of Beva from PZA@Beva exhibited pH-dependent kinetics. In vitro, PZA@Beva demonstrated effective penetration across the ocular barrier via both the paracellular pathway (by opening corneal tight junctions) and the transcellular pathway (through rapid cellular endocytosis). Additionally, PZA@Beva exhibited no cytotoxicity in vitro or in vivo, coupled with prolonged ocular retention, collectively yielding promising results for the treatment of CNV. This study contributes to non-invasive protein delivery across ocular bio-barriers for the treatment of diseases in the anterior segment.
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ENVIRONMENTAL SCIENCE & TECHNOLOGY
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2025
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IF 11.3
Wen Xie,Yajing Zhang,Yu He,Hang Su,Jinni Zhang,Canrong Chen,Peisi Xie,Jing Chen,Zian Lin,Zongwei Cai
Imidacloprid (IMI), a neonicotinoid insecticide extensively applied in agriculture, is among the most frequently detected pesticides in food. However, the long-term impact of chronic dietary exposure to environmentally relevant IMI doses on kidney health has not been fully elucidated, particularly regarding its nephrotoxic mechanisms. To address this gap, chronic exposure to IMI was administered to mice through supplementation of their feed with environmentally relevant doses (approximately 100 and 1000 μg/kg/day) for 24 weeks to investigate its nephrotoxicity and underlying mechanisms. Toxicological analysis revealed that chronic IMI exposure led to renal dysfunction, histopathological alterations, and excessive apoptosis in mice. Mechanistic investigations suggested that IMI might inhibit AMP-activated protein kinase (AMPK) activity through both direct and indirect pathways. Direct inhibition occurred through the binding of IMI and its metabolites to AMPK, reducing its phosphorylation activity. Indirect inhibition involved excessive production of reactive oxygen species, which suppressed AMPK phosphorylation, leading to sustained purine metabolism dysregulation in the renal system. Consequently, the kidneys showed an aggravated redox imbalance, heightened inflammatory states, and increased cellular apoptosis. The results of this study are intended to raise awareness of pesticide use and food safety among agricultural workers and consumers.
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Scientific Reports
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2025
·Vol. 15
·期 1
·1-10
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IF 3.9
Shen Fangzhou,Lu Zhaoyang,Yan Kangli,Luo Kang,Pei Shuchen,Xiang Pu
This work reports a novel one-pot hydrothermal synthesis of N-CQDs using Solanum nigrum L . as sustainable carbon source and triethylamine as nitrogen provider. The resulting N-CQDs were systematically characterized with TEM, SEM, FT-IR, XPS, XRD, and UV–Visible. Significantly, the N-CQDs exhibited substantial antimicrobial efficacy against both S. aureus and E. coli bacterial strains, with minimum inhibitory concentration values of 1.2 mg/mL and 1.1 mg/mL, respectively. Moreover, the N-CQDs demonstrated pronounced fluorescence enhancement upon interaction with ciprofloxacin, displaying exceptional selectivity and sensitivity, with a calculated LOD of 316 nM. The feasibility of employing N-CQDs as fluorescent probes for ciprofloxacin detection was systematically validated through practical application in honey analysis. This study introduces a novel approach for the fabrication of N-CQDs derived from natural botanical sources, underscoring their potential dual functionality as fluorescent sensors and antimicrobial materials.
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Cancer Communications
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2025
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IF 24.9
Jie Zhang,Chen Zhang,Ruichen Zang,Weiwu Chen,Yining Guo,Haofei Jiang,Jing Le,Kunyu Wang,Haobo Fan,Xudong Wang,Sisi Mo,Peng Gao,Wenhao Guo,Xinrong Jiang,Fengbin Gao,Junming Jiang,Juyan Zheng,Yuxing Chen,Yicheng Chen,Yanlan Yu,Guoqing Ding
Background: Only a few bladder cancer patients benefit from anti-programmed cell death protein 1/programmed cell death ligand 1 immunotherapy. The cluster of differentiation 47 (CD47) plays an important role in tumor immune evasion. CD47 is a highly glycosylated protein, however, the mechanisms governing CD47 glycosylation and its potential role in immunosuppression are unclear. Therefore, this study aimed to evaluate the function of CD47 glycosylation in bladder cancer. Methods: Western blotting, immunohistochemistry, and flow cytometry were used to measure protein expression, protein-protein interactions, and phagocytosis in bladder cancer. A murine model was employed to investigate the impact of mannosidase alpha class 1B member 1 (MAN1B1) modification of CD47 on anti-phagocytosis in vivo. An ex vivo model, patient-derived tumor-like cell clusters, was used to examine the effect of targeting MAN1B1 on phagocytosis. Results: Our research identified that aberrant CD47 glycosylation was responsible for its immunosuppression. The glycosyltransferase MAN1B1 responsible for CD47 glycosylation was highly expressed in bladder cancer. Abnormal activation of extracellular signal-regulated kinase (ERK) was significantly associated with MAN1B1 stability by regulating the interaction between MAN1B1 and the E3 ubiquitin ligase HMG-CoA reductase degradation 1 (HRD1). Mechanistically, abnormally activated ERK stabilized MAN1B1, resulting in the glycosylation of CD47 and facilitating immune evasion by enhancing its interaction with signal-regulatory protein alpha (SIRP-α). In vitro and in vivo experiments demonstrated that MAN1B1 knockout weakened CD47-mediated anti-phagocytosis. MAN1B1 inhibitors promoted phagocytosis without causing anemia, offering a safe alternative to anti-CD47 therapy. Conclusions: This comprehensive analysis uncovered that ERK activation stabilizes MAN1B1 by regulating the interaction between MAN1B1 and HRD1, facilitates immune evasion via CD47 glycosylation, and presents new potential targets and strategies for cancer immunotherapy that do not cause anemia.
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