Materials Today Bio
·
2025
·
IF 10.2
Han Shi,Zhiqiang Xie,Junrong Zhang,Fengchun Lu,Haoteng Luo,Pengfei Guo,Meichen Jiang,Zongqi Weng,Xin Luo,Bing Chen,Heguang Huang,Tianhong Teng
Reprogramming of branched-chain amino acid (BCAA) metabolism is a key mechanism promoting pancreatic cancer progression. While gabapentin (Gp) can inhibit BCAA catabolism by targeting branched-chain amino acid aminotransferase 1 (BCAT1), its efficacy is limited by inefficient delivery and compensatory mitochondrial metabolism. To address this, we developed a novel copper ionophore-functionalized mesoporous silica nanoplatform (XQ/Gp@CMSNs) for synergistic cuproptosis and tumor-starvation therapy. The designed nanoparticles exhibit excellent pancreatic cancer-targeting capability via XQ-2d aptamer modification and acid-responsive drug release within the tumor microenvironment. Upon internalization, XQ/Gp@CMSNs simultaneously induce mitochondrial copper overload and disrupt BCAA metabolism, leading to dihydrolipoamide S-acetyltransferase (DLAT) oligomerization, ferredoxin 1 (FDX1) downregulation, and tricarboxylic acid (TCA) cycle suppression. Both in vitro and in vivo studies demonstrated potent antitumor efficacy with minimal systemic toxicity. Metabolomic analyses further confirmed synergistic BCAA metabolic inhibition and copper-induced mitochondrial dysfunction. This work presents a promising metabolic intervention strategy for pancreatic cancer through targeted nanomedicine.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Pharmaceutics-X
·
2025
·
IF 6.4
Teng Xiao,Fanghong Wang,Ye Li,Gaoyang Lin,Xiaochen Wu
Acute kidney injury (AKI) is a severe clinical condition with high morbidity and mortality, often triggered by nephrotoxic drugs like cisplatin. The cGAS/STING pathway, activated by DNA damage, plays a critical role in cisplatin-induced AKI. This study explores the potential of phloretin-loaded selenium nanoparticles (Phl/HS15-Se) as a therapeutic strategy to mitigate cisplatin-induced nephrotoxicity. Phloretin, a natural flavonoid with antioxidant properties, was encapsulated in polyethylene glycol (15)-hydroxy stearate (HS15) micelles and combined with selenium nanoparticles to enhance its renal protective effects. The in vitro and in vivo experiments demonstrated that Phl/HS15-Se significantly reduced oxidative stress, DNA damage, and inflammation by inhibiting the cGAS/STING pathway. In a cisplatin-induced AKI mouse model, Phl/HS15-Se alleviated renal pathological injury, improved renal function, and reduced the expression of inflammatory markers. This study provides a promising nanomedicine approach for the treatment of cisplatin-induced AKI by targeting the cGAS/STING pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2025
·
IF 4.7
Conglu Zhao,Liyuan Ji,Xiaoting Wang,Jia Zhang,Xiang Xu,Xiaoting Zhang,Yanjie Ding,Keran Li,Chaoyue Zheng,Kaijun Qiu,Jing Yan,Songtao Gu,Honggang Zhou,Cheng Yang,Hongli Li,Xiaoting Gu,Xiaoyu Ai
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung lesion, which is called a "tumor-like disease". Previous studies have confirmed that intratracheal instillation of formononetin-loaded porous microspheres (FMN-PLGA-MSs) can effectively improve bleomycin-induced pulmonary fibrosis. However, the poor lung retention of FMN-PLGA-MSs reduces the therapeutic efficacy of the FMN. Building on this foundation, this study prepared chitosan-coated formononetin porous microspheres (CS-FMN-PLGA-MSs) to enhance the FMN lung retention by leveraging the bioadhesive properties of chitosan. It is expected to prolong the action time of formononetin in lung tissues and enhance the therapeutic efficacy for pulmonary fibrosis. The study results showed that, compared to FMN-PLGA-MSs, CS-FMN-PLGA-MSs could be better taken up by MLG cells and NIH-3T3 cells. In vivo imaging demonstrated that CS-FMN-PLGA-MSs had a prolonged lung retention time, lasting up to 48 h. CS-FMN-PLGA-MSs exhibited a greater deposition in the regions of lung tissue compared to FMN-PLGA-MSs. The in vivo efficacy results in bleomycin-induced pulmonary fibrosis mice showed that, compared to FMN-PLGA-MSs, CS-FMN-PLGA-MSs had a higher anti-pulmonary fibrosis efficacy, significantly reducing hydroxyproline levels in fibrotic lung tissues, decreasing the extent of pulmonary fibrosis, and improving lung function. CS-FMN-PLGA-MSs provide a new reference for the treatment of pulmonary fibrosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL RESEARCH
·
2025
·
IF 4.3
Bai Wanting,Li Yang,You Feng,Duan Xiaoyan,Hu Jiahuan,Wu Jinjin,Sun Tao,Wang Xing,Lan Pei,Hu Jinping
Objective Bicyclol, a hepatoprotective agent, is often used in combination with other drugs for liver diseases, including drug-induced liver injury (DILI), raising concerns about potential drug-drug interactions (DDIs). This study investigates the interaction between bicyclol and key transporters (OATP1B1, OATP1B3, OAT1, OAT3, OCT2, MATE1, MATE2-K, P-gp, BCRP, BSEP) to predict transporter-related DDI risks. Methods Transporter interaction studies were conducted using cell lines or membrane vesicles overexpressing human uptake and efflux transporters. The substrate and inhibitory potential of bicyclol were systematically evaluated through transport and inhibition assays. The static model and criteria were applied to assess the risk of transporter-related DDIs in vivo . Results Bicyclol was not a substrate of above-mentioned transporters. Regarding inhibition, it was not an inhibitor of OATP1B1, OATP1B3, OAT1, OAT3, MATE1, MATE2-K, or BSEP (IC 50 s > 100 μM). However, it was a marginal inhibitor of OCT2 (IC 50 = 76.2 μM), a weak inhibitor of P-gp (IC 50 = 123 μM), and a strong inhibitor of BCRP (IC 50 = 8.5 μM). The static model predicted that only BCRP would be inhibited in vivo by bicyclol, suggesting dose optimization might be required for BCRP substrates. Conclusions Here, we systematically elucidated the substrate and inhibition potential of bicyclol on major human drug transporters for the first time, which may provide the basis for rational co-administration of bicyclol, potentially broadening its clinical application.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2025
·
IF 8.2
Lang Liu,Jingyu Weng,Lei Yue,Yuanyuan Qin,Jia Yu,Yaqi Li,Shuming Li,Jiaofeng Wu,Yuangui Yang,Zhishu Tang,Hongbo Xu
Cerebral ischemia–reperfusion injury exacerbates neuronal loss following acute ischemic stroke through oxidative stress and regulated cell-death pathways, notably ferroptosis. Here, we investigated whether rosmarinic acid (RA), a natural polyphenol, confers neuroprotection by inhibiting ferroptosis via activation of the KEAP1–NRF2 axis. In vivo , rats pretreated with RA (30 or 60 mg/kg, i.p.) for 14 days before middle cerebral artery occlusion/reperfusion exhibited dose-dependent improvements in neurological scores, reduced infarct volumes, preserved cerebral blood flow, and attenuated histopathological damage. In vitro , RA (25–50 μM) restored the viability of HT22 and PC12 cells subjected to oxygen-glucose deprivation/reperfusion, suppressed lipid reactive oxygen species accumulation, iron overload, and mitochondrial ultrastructural collapse. Mechanistically, RA promoted nuclear factor erythroid 2-related factor 2 (NRF2) nuclear translocation, enhanced antioxidant response element -driven luciferase activity, and upregulated ferroptosis-defense genes ( Gpx4 , Slc7a11 , and Gclm ) at both mRNA and protein levels. Cycloheximide chase and ubiquitination assays, supported by molecular docking, molecular dynamics simulations, and surface plasmon resonance, demonstrated that RA directly binds Kelch-like ECH-associated protein 1 (KEAP1) to stabilize NRF2. A KEAP1 knockdown abolished RA's induction of NRF2 targets and its anti-ferroptotic effects. These findings establish RA as a targeted NRF2 activator and ferroptosis inhibitor, offering a promising therapeutic strategy for limiting ischemia–reperfusion-induced neuronal injury.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ASIAN JOURNAL OF ANDROLOGY
·
2025
·
IF 2.7
Zheng Cheng-Hao,Wang Wen-Hao,Ji Shi-Yu,Jing Yi-Feng,Han Bang-Min,Xia Shu-Jie,Wang Xing-Jie
Postoperative wound repair after transurethral resection of the prostate (TURP) in benign prostatic hyperplasia (BPH) patients is crucial for reducing complications and promoting recovery. Androgens, particularly dihydrotestosterone (DHT), influence prostatic development and wound healing, with type II 5α-reductase (5αR2) playing a key role in DHT synthesis. In this study, the effects of type II 5α-reductase inhibitors (5-ARIs) on postoperative healing, inflammation control, and fibrosis reduction were evaluated. A double-blinded randomized clinical trial was performed to assess 87 BPH patients treated with type II 5-ARIs (n = 47) or placebo (n = 42) over six months. The type II 5-ARIs group presented a 55.0% lower complication rate (P = 0.002), with reduced hematuria (0 vs 7.1%, P = 0.046) and catheter reintroduction (0 vs 9.5%, P = 0.025). An animal study using 12 beagles was performed, and molecular markers were analyzed via single-cell RNA sequencing, enzyme-linked immunosorbent assay (ELISA), and histology. 5αR2 inhibition accelerated urothelial regeneration, decreased inflammation, and reduced myofibroblast activation by 42.0% while increasing the expression of the urothelial marker uroplakin 3A (UPK3A) by 67.0%. Organoid experiments confirmed increased urothelial differentiation and reduced glandular epithelial expansion with type II 5-ARI treatment. These findings suggest that 5αR2 inhibition promotes TURP postoperative recovery in BPH patients by reducing inflammation, inhibiting fibrosis, and promoting wound repair. These findings support the use of type II 5-ARIs as potential adjuvant therapies for optimizing BPH patient postoperative outcomes.
✓ 已验证
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2025
·
IF 8.2
Kunmei Xie,Jingquan Dong,Xiguang Liu,Xiao Liu,Shasha Zhang,Yan Cao,Long Chen,Wanyi Xu,Panpan Zhao,Zibo Dong
Sepsis is a life-threatening systemic inflammatory response syndrome with high morbidity and mortality. A frequent complication is sepsis-associated encephalopathy (SAE), characterized by neurological impairments. Microglia pyrin domain- containing receptor 3 (NLRP3) inflammasome activation is a pivotal pathogenic mechanism in SAE. Microtubule-affinity regulating kinase 4 (MARK4) has been implicated in neuroinflammatory diseases, but its role in SAE and microglial NLRP3 inflammasome activation is unclear. Sophoridine (SRI), a MARK4 antagonist with anti-inflammatory and neuroprotective properties, has not yet been thoroughly investigated in SAE. Here, we used a cecum ligation puncture (CLP)-induced SAE mouse model and LPS+ATP or LPS+ nigericin (Nig)-treated microglia, to assess the role of MARK4 in SAE. Molecular docking, Nissl staining, the enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and behavioral tests were applied to assess SRI’s effects on SAE. Our findings demonstrate that MARK4 is significantly upregulated in SAE. Knockdown of MARK4 effectively suppressed microglial pyroptosis and pro-inflammatory cytokine release by inhibiting NLRP3 inflammasome activation. SRI binds to MARK4 and enhances its stability. By suppressing MARK4 protein expression, SRI reduces NLRP3 inflammasome-mediated microglia inflammation. In vivo , SRI treatment increased survival, improved neurological behavioral deficits, attenuated blood-brain barrier disruption, and provided neuroprotective effects against brain injury. In summary, MARK4 contributes to microglial pyroptosis and neuroinflammation through NLRP3 pathway in SAE, resulting in neuronal injury and cognitive impairment. SRI alleviates SAE by targeting MARK4. These results suggest MARK4 as a potential therapeutic target and SRI as a promising candidate for treating SAE.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
·
2025
·
IF 5.2
Jiajie Hu,Alice Giusti,Yi Hu,Yao Zhang,Gabriele Spatola,Lara Tinacci,Xiaoguo Ying,Andrea Armani
Microbial spoilage is a major contributor to seafood quality deterioration, posing major challenges to freshness preservation. In this study, we investigated how atmospheric cold plasma (ACP) treatment influenced the freshness, volatile compounds (VCs), and microbial properties of red shrimp surimi-based product (RSSP) during refrigerated storage. The results demonstrated that ACP treatment had no significant impact ( p > 0.05) on the color attributes, texture properties, or pH of RSSP on day 0 compared to the untreated group. However, notable changes were observed in the VCs, including increases in 2-butanone-D and 1-pentanol, and a decrease in ethyl acetate-D, suggesting mild oxidative modifications. Notably, ACP significantly ( p < 0.05) reduced total viable count and psychrotrophic viable count by 62.53 % and 65.82 %, respectively. Over the storage period, ACP-treated samples exhibited delayed proliferation of Shewanella and Brochothrix , leading to a reshaped bacterial community structure during the mid- to late storage stages, which delayed the accumulation of spoilage-related VCs such as trimethylamine and ammonia. Additionally, ACP-induced oxidative stress influenced the ecological assembly of the bacterial community, shifting from a stochastic process in the early stage of storage to a more deterministic trajectory later on. Correlation analysis identified Psychrobacter , Shewanella , and Brochothrix as key contributors to quality decline, although causality requires further investigation. Overall, ACP treatment effectively inhibited microbial spoilage progression and helped maintain the freshness of RSSP.
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2025
·
IF 12.5
Jinyan Gu,Mouming Zhao,Lijun You,Lianzhu Lin
The colon immune activity of high branched rhamnogalacturonan-I type pectin from Lycium barbarum fruit (LBP-P4) was unclear. This study comparatively investigated the colon immunity activity of LBP-P4 and inulin and explored its mechanism via simulated colon biological and mechanical barriers models. LBP-P4 could be slowly degraded and utilized by intestinal microorganisms with degradation rate of 88.88 %. Meanwhile, LBP-P4 increased the relative abundance of Bifidobacterium, especially Bifidobacterium longum subsp. longum , which was confirmed by single Bifidobacterium fermentation. In the normal colon mechanical barrier coupled with macrophage model, the colonic metabolites of LBP-P4 enhanced macrophage viability and phagocytic ability. In the damaged colon mechanical barrier coupled with macrophage model, the colonic metabolites of LBP-P4 enhanced mechanical barrier integrity, reduced the production of NO and IL-6 and improved macrophage viability and phagocytic ability. The colon immunity activity of LBP-P4 was stronger than that of inulin, which was because the contents of immunity related metabolites i.e. short chain fatty acids and tryptophan metabolites, were significantly higher (about 1–3 fold) in LBP-P4 group than those in inulin group. Our findings provided new insights into the probiotic and intestinal immunity function of LBP-P4 and offered theoretical basis for the development of functional products of LBP-P4.
✓ 已验证
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2025
·
IF 7.5
Yuna Tong,Xiuxiu Li,Yuxuan Zhu,Xiaohui Liao,Ling Zhang
The critical pathogenic factors in the initiation and progression of diabetic nephropathy (DN) include hyperglycemia, oxidative stress, and inflammatory responses. Current therapeutic interventions for DN remain constrained by the intricate pathophysiological mechanisms that are involved in the dysregulations of multiple renal signaling pathways. Zinc (Zn) is an essential trace element that participates in diverse physiological processes, exhibits protective effects against oxidative stress-induced apoptosis, and plays a pivotal role in insulin biosynthesis and secretion. In our exploratory study, we aimed to develop targeted intervention in diabetes-associated DN pathogenesis by engineering metformin (MET)-encapsulated Zn-MOF nanoparticles conjugated with a renal-targeting protein (KTP-Zn-MOF/MET). In vivo imaging analyses revealed that renal accumulation of these multifunctional nanoparticles was significantly enhanced in BALB/c nude mice. The nephroprotective efficacy was preliminary explored in a rat model with renal injury induced using streptozotocin. Intravenous administration of KTP-Zn-MOF/MET ameliorated multiple DN-related pathological manifestations, including renal functional impairment, cellular apoptosis, lipid peroxidation, and oxidative stress. Our findings indicated that KTP-Zn-MOF/MET is a novel therapeutic strategy for precise renal targeting and multi-target intervention in DN management, with significant potential for clinical translation.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
·
2025
·
IF 5.2
Junhua Wang,Shunxin Qin,Leilei Chen,Liang Wang,Xiangyan Chen,Jiying Qiu,Xingwang Zhang,Wenjuan Zhang,Qingxin Zhou
Botrytis cinerea , the second prevalent fungal pathogen worldwide, threatens a wide range of plants through its aggressive gray mold infection. This study investigates the antifungal effect of nerol against B. cinerea . Its minimum inhibitory concentration is 0.25 mL/L. Colony diameter reduced by 88.86 % at 48 h. Nerol exposure induced ROS accumulation, increasing malondialdehyde levels, which disrupted membrane integrity. It further induced mitochondrial dysfunction by suppressing the enzyme activities of succinic dehydrogenase and citrate synthase, reducing membrane potential, and promoting cytochrome C release and caspase-3 activation. Combined with phosphatidylserine externalization, these results suggested that nerol inhibited the growth of B. cinerea by a mitochondrial apoptosis pathway. Nerol regulated autophagy-related genes expression and activated autophagy. In postharvest cherry tomatoes, nerol controlled gray mold on postharvest fruits by inhibiting the growth of B. cinerea , but also inducing fruit resistance by elevating phenolic content by 50.13 %. The study elucidates nerol's multifaceted antifungal and fruit-protective effects against B. cinerea , supporting its development for the postharvest preservation of cherry tomatoes.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Radiation Research and Applied Sciences
·
2025
·
IF 2.5
Yu Zhang,Hongbo Lv,Chao Chen,Zixu Li,Zhaoyu Xie,Miaomiao Wu,Zhixu Zhu,Ying Fan,Jing Li,Qiang Gao,Jun Han,Hui Che,Lan Ma
Background Ischemic stroke (IS) is a major global cause of mortality and long-term disability, and effective therapies are urgently needed. Hydrogen sulfide (H 2 S) has shown neuroprotective effects in various neurological disorders, but its mechanisms in IS remain unclear. This study aims to explore the role and mechanism of H 2 S in IS treatment. Methods IS models were established in vivo using middle-cerebral-artery occlusion (MCAO) in rats and in vitro using oxygen-glucose deprivation/reoxygenation (OGD/R) in PC12 cells. These models were treated with H 2 S donors NaHS or GYY4137. Pathological features were evaluated using TTC, FJC, H&E, and Nissl staining. Cell viability was assessed with live/dead staining and CCK-8 assay. RNA sequencing identified gene expression changes after H 2 S treatment under OGD/R conditions. Ferroptosis-related markers, lipid peroxidation (GSH, SOD, MDA), ROS levels, and the expression of SLC7A11 and GPX4 were measured by flow cytometry, Western blot, and immunofluorescence. MiR-27a levels were quantified by qRT-PCR. Results NaHS administration in MCAO rats reduced infarct volume, increased Nissl body density, and decreased degenerating neurons. GYY4137 exhibited similar neuroprotective effects in vitro. RNA sequencing revealed that GYY4137 reversed ferroptosis-related gene changes, including SLC7A11. H 2 S supplementation inhibited neuronal ferroptosis, shown by increased SLC7A11 and GPX4 expression, elevated GSH and SOD levels, and reduced MDA content. Additionally, MCAO or OGD/R induced miR-27a expression, which negatively regulated SLC7A11. H 2 S reversed this induction, and miR-27a overexpression partially blocked the anti-ferroptotic effect of H 2 S. Conclusion H 2 S alleviated IS-induced brain injury by suppressing ferroptosis, partially through miR-27a-dependent regulation of SLC7A11. These findings suggest H 2 S as a promising therapeutic agent for IS, warranting further clinical exploration.
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）