LIFE SCIENCES
·
2019
·
IF 3.448
Runxiao Lv,Lili Du,Xueyong Liu,Fenghua Zhou,Zhiqiang Zhang,Lixin Zhang
Inflammation contributes to the pathological processes in patients and animal models of PD. Rosmarinic acid (RA) has been demonstrated to protect neurons in PD models. The present study aimed to evaluate the anti-inflammatory effect of RA on PD and reveal possible pharmacological mechanisms. 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) was injected to mice to establish PD model in vivo. BV-2 cells were exposed to 1-methyl-4-phenylpyridinium (MPP + ) and α-synuclein to establish PD model in vitro. Results showed that treatment with RA dose-dependently improved motor function of PD mice, increased the number of tyrosine hydroxylase-positive cells, reduced production of pro-inflammatory cytokines, and inhibited microglia activation in ventral midbrain. In cell study, RA also decreased MPP + or α-synuclein-induced secretion of pro-inflammatory cytokines. Furthermore, RA treatment downregulated the expression levels of HMGB1, TLR4 and Myd88 and inhibited NF-κB nuclear expression both in PD animal and cell models. These findings indicated that RA could attenuate inflammatory responses through suppressing HMGB1/TLR4/NF-κB signaling pathway, which may contribute to its anti-PD activity.
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INTEGRATIVE CANCER THERAPIES
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2022
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IF 3.077
Debapriya De,Priyanka Chowdhury,Sujogya Kumar Panda,Utpal Ghosh
Background: Different parts of Dillenia pentagyna have long been used in traditional medicines to cure several diseases including cancer. However, the mechanism(s) of anti-cancer effects are still unknown. We aimed to elucidate the anti-metastatic potential of ethanolic extracts of leaves of D. pentagyna (EELDP) and active fractions of it in highly metastatic human cancer cells. Methods: We screened different HPLC fractions of EELDP based on their anti-metastatic effect. We used TLC and ESI-MS for determining the presence of various phytochemicals in EELDP and fractions. We monitored in vitro anti-metastasis effect of EELDP (0-0.6 mg/ml) and active fractions (0-0.050 mg/ml) on various human cancer cells like A549, HeLa, and U2OS. Results: EELDP significantly reduced cell viability and cell migration in A549, HeLa, and U2OS cells. However, higher sensitivity was observed in A549 cells. We screened 2 active HPLC fractions F6 and F8 having anti-MMPs activity. EELDP and active fractions reduced metastasis via the NF-κB pathway, decreased the expression of Vimentin, N-cadherin, and increased the expression of Claudin-1. Conclusion: Significant reduction of metastasis by EELDP at a dose of 0.1 mg/ml or by active fractions at 0.050 mg/ml implicates that the active compound(s) present in crude or fractions are extremely potent to control highly metastatic cancer.
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MICROBIAL PATHOGENESIS
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2024
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IF 3.3
Zhikun Zhang,Dawei Shi,Haiwei Dou,Ruijie Wan,Qing Yuan,Peng Tu,Deli Xin
In previous study, lower levels of serum GP130 were reported in children with MPP. GP130 is an important signal transducer, the down regulation of which may influence host immune responses. In this study, we aimed to analyze the regulatory mechanism of GP130 during MP infection. Firstly, the mRNA and protein levels of GP130 both decrease and then increase with increasing multiplicity of infection (MOI: 1 to 40) of MP. The lowest levels of GP130 were detected at MOI of 5. Then, heat treated MP but not trypsin treated MP or MP extracted proteins show regulatory effect to the expression of GP130. These indicate that the down regulation of GP130 is related to protein mediate adhesion process of MP. Gene expression analysis revealed that MP affected apoptosis and the TLR4 pathway in infected cells, and the mRNA level of IL-6 was correlated with that of GP130. Further, Z-VAD-FMK (pan-caspase inhibitor) can suppress the apoptosis induced by MP infection and restore GP130 at protein level. Further studies revealed that MP infection promoted TLR4 internalization but did not activate the NF-κB pathway. The levels of surface TLR4 showed correlation with the transcription of IL-6 and GP130. TAK242 (TLR4 inhibitor) and PS341 (proteasome inhibitor) can restore the decreased transcription of GP130, both of which were able to promote NF-κB pathway activation in MP-infected cells. These suggested that the regulation of TLR4/NF-κB pathway and induced apoptosis post MP infection are involved in the down-regulation of GP130 at transcription and protein levels, respectively.
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JOURNAL OF ALZHEIMERS DISEASE
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2025
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IF 3.1
Yanyu Zhai,Kaili Lu,Yuan Yuan,Ziyao Zhang,Lixia Xue,Fei Zhao,Xiaofeng Xu,Hongmei Wang
BackgroundAlzheimer's disease (AD) causes cognitive function disorder and has become the preeminent cause of dementia. Glucagon-like peptide-1 (GLP-1) receptor agonists, semaglutide, have shown positive effects on promoting the cognitive function. However, research about the mechanism of semaglutide as a therapeutic intervention in AD is sparse.ObjectiveThis study was to investigate the therapeutic efficacy of semaglutide in a transgenic mouse model of AD pathology and explored the detailed mechanism by semaglutide modulated neuroinflammatory processes.MethodsMale amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice were treated with semaglutide or vehicle for 8 weeks. Morris water maze test was used to assess the therapeutic efficacy of semaglutide on recognition function. Pathology analysis was performed to detect the deposition of amyloid plaques. High-throughput sequencing analysis was applied to specify the mechanism. Microglia and astrocyte activation were assessed with immunofluorescent staining. Inflammation cytokine levels were evaluated with enzyme-linked immunosorbent assay (ELISA). Related proteins and pathway were evaluated with western blot.ResultsSemaglutide treatment attenuated Aβ accumulation and enhanced cognitive function in APP/PS1 transgenic mice. Through transcriptomic profiling, immunohistochemical staining, and ELISA, semaglutide was substantiated to inhibit the overactivation of microglia and astrocytes, as well as to curtail the secretion of inflammatory mediators. Furthermore, semaglutide robustly activated AMP-activated protein kinase (AMPK) and suppressed the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling cascade, thus reducing the Aβ deposition and dampening the inflammatory cascade.ConclusionsThe results demonstrated that semaglutide mitigated neuroinflammation and decelerated the advance of AD in APP/PS1 transgenic mice.
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Biomedicines
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2026
·Vol. 14
·期 7
·1586
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IF 4.5
Xiaofei Tong,Meina Sun,Xin Gan,Xin Chen,Shiyang Liu,Ieong Sun,Lin Zhang,Weihong Zheng
Background: Capsular contracture is driven by self-amplifying foreign body response (FBR) where inflammatory and fibrotic signals from fibroblasts and macrophages reinforce each other. We hypothesized that cogradient simultaneous blockade of NF-κB as an inflammatory node and TGF-β/Smad as fibrotic node could attenuate the FBR. Emodin has dual inhibitory activity but suffers from poor delivery.Methods: Emodin liposomes (Emo-Lip) were characterized and tested on TGF-β1-stimulated NIH/3T3 fibroblasts and LPS-stimulated RAW264.7 macrophages. In a rat silicone implant model, periprosthetic injections were given for four weeks. Fibrous capsule formation was evaluated by histology, immunofluorescence, and FAPI-PET/CT. Transcriptomic analyses were performed to verify and predict relevant pathways.Results: Emo-Lip had uniform size and high encapsulation efficiency. In vitro, Emo-Lip inhibited fibroblast migration, ROS production, myofibroblast differentiation (α-SMA+) as well asCtgfexpression, while suppressing M1 polarization and reduced IL-12/IL-6 secretion in macrophages. In vivo, Emo-Lip reduced capsule thickness, collagen area, and α-SMA/Col I expression, comparable to dexamethasone. Transcriptomics showed coordinated downregulation of inflammatory/fibrotic genes, and Western blot confirmed suppressed phosphorylation of Smad3.Conclusions: Coordinated two-node blockade of NF-κB and TGF-β/Smad by liposomal emodin reprograms the FBR and effectively prevents capsular contracture in rats, offering a translational strategy for implant-associated fibrosis.
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ACS Catalysis
·
2026
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IF 13.6
Chenkun Zheng,Jianan Li,Dong Zhang,Yi Liu,Yin Wang,Xiaodi Wang,Yun-Xiang Pan,Chong Peng
Coupling the hydrogen evolution reaction (HER) with PET-derived ethylene glycol oxidation reaction (EGOR) offers an energy-saving route for hydrogen production and plastic upcycling. However, Pt-based bifunctional catalysts are limited by inefficient Pt utilization, nonideal H* adsorption, and anodic oxidation-induced deactivation. Here, we report an oxygen-deficient D-Pt-Ni(OH)2/NF catalyst prepared by dielectric barrier discharge plasma treatment and integrated with an alternating-pulse electrolysis strategy. Plasma treatment introduces abundant oxygen vacancies and promotes electron transfer from Ni to Pt, downshifting the Pt d-band center and optimizing H* adsorption. The optimized catalyst requires only 12 mV to reach 10 mA cm–2 for HER and delivers a Pt mass activity of 3.23 A mg–1Pt at –0.1 V vs RHE, which is 64.6 and 1.68 times higher than those of Pt/C and untreated Pt-Ni(OH)2/NF, respectively. In an HER||EGOR electrolyzer, D-Pt-Ni(OH)2/NF achieves 100 mA cm–2 at 0.96 V using PET hydrolysate. Alternating-pulse electrolysis suppresses Pt oxidation and enables stable 100 h operation in a membrane-free flow electrolyzer, with >90% Faradaic efficiency for glycolic acid and nearly 100% Faradaic efficiency for H2. Techno-economic analysis indicates a net profit of $1080.1 per ton of PET processed. This work demonstrates a catalyst–electrolysis co-engineering strategy that links plasma-induced electronic modulation with durable plastic valorization-assisted hydrogen production.
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ACS Applied Materials & Interfaces
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2026
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IF 8.2
Mingjing Wang,Kang Liu,Peng She,Tianci Gao,Zhansen Shi,Yunlai Wang,Xiaoya Ding,Ye Yang,Dengke Yin,Wei Shen,Hanmeng Liu
Rheumatoid arthritis (RA) tissues exhibit high levels of reactive oxygen species (ROS) and free Ca2+, which contribute to a vicious cycle of sustained inflammatory responses. This study developed an in situ Ca2+-reinforced injectable full-active HPAP hydrogel. The full-active hydrogel is formed by cross-linking phenylboronic acid-functionalized hyaluronic acid (HA-PBA) with sodium alginate (ALG) and paeoniflorin (PF) through boronate ester bonds, all of which play significant roles in RA treatment. HPAP hydrogel exhibits relatively low strength in vitro, allowing for easy injection into the joint cavity. Then, ALG can trigger secondary cross-linking in the RA joint cavity using Ca2+, forming the HPAP/Ca2+ hydrogel in situ and enhancing drug retention (with significant signals detectable in vivo even 17 days postinjection). Furthermore, a decrease in the free Ca2+ concentration can inhibit the activation of the NLRP3 inflammasome pathway. HA-PBA participates in the formation of ROS-responsive boronate ester bonds in hydrogel, thereby reducing ROS levels in RA tissues. Additionally, the released PF inhibits the activation of the NF-κB pathway, mitigating the inflammatory response. In vitro and in vivo experiments demonstrate that the HPAP hydrogel can effectively scavenge ROS, inhibit the NF-κB and NLRP3 pathways, reprogram macrophages, and reduce osteoclast differentiation and cartilage matrix degradation. In the RA animal models, HPAP hydrogel significantly improved arthritis scores, bone erosion, and inflammation levels, showing better treatment efficacy compared to commercial dexamethasone. Given the simplicity of the components of this full-active hydrogel, all of which are natural and safe compounds, it exhibits promising clinical translation potential in RA treatment.
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2026
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IF 2.5
Zhen Yang,Huiying Li,Wei Zhao,Yingxia Yu,Yanling Lin,Jianxuan Liu,Xinghu Fan,Moyan Wang,Xin Teng,Zhikai Qiu
Objective Evaluation of the therapeutic effect of Tongfu Zhike Formula (TFZKF) on mice with cough variant asthma (CVA) and exploration of its mechanism of action in improving CVA. Methods The main chemical components of TFZKF were detected and analyzed using UHPLC-MS/MS. Network pharmacology was employed to investigate the potential targets of TFZKF in CVA. After grouping and drug administration, the number of coughs and cough latency were observed in CVA mice. White blood cell differential counts in BALF, serum levels of IgE, IL-4, IL-5, IL-13 and IFN-γ, as well as pathological changes in lung tissue were assessed. Western blot and RT-qPCR were used to analyze the protein expression levels and mRNA changes of TLR4, MyD88, and NF-κB in the lung tissue of CVA mice. Results A total of 495 chemical components were detected in TFZKF under both positive and negative ion modes. Network pharmacology analysis identified 199 potential targets related to TFZKF and CVA, and found close associations with the TLR4 and NF-κB signaling pathways. Animal experiments showed that, compared to the Model group, TFZKF significantly reduced the number of coughs, prolonged cough latency, decreased serum levels of IgE, IL-4, IL-5, and IL-13, reduced the total number of white blood cells, neutrophils, and eosinophils in BALF, alleviated inflammatory cell infiltration and fibrosis in lung tissue, and downregulated the protein and mRNA expression of TLR4, MyD88, and NF-κB. Conclusion The interaction within the TLR4/MyD88/NF-κB signaling pathway may be a potential key target for the treatment of cough variant asthma.
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Scientific Reports
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2026
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IF 4.9
Li Ruifang,Sun Yan,Feng Mingzhi,Kelsang Drolma,Cai Hanhui,Zhang Jun
Ulcerative colitis (UC) is a chronic disease characterized by intestinal inflammation, mucosal damage, and immune dysregulation. Current treatments are often inadequate, driving the search for alternatives with fewer side effects. Isoliquiritigenin (ISL), a flavonoid from licorice, has demonstrated anti-inflammatory effects, but its efficacy in UC remains uncertain. Male C57BL/6 mice were divided into six groups: Control, DSS model, low-, medium-, and high-dose ISL (25, 50, 100 mg/kg), and 5-aminosalicylic acid (5-ASA, 100 mg/kg). UC was induced by administering 3% DSS, followed by ISL or 5-ASA treatment. Disease activity index (DAI), histopathology, real-time PCR, Western blotting, immunohistochemistry, and 16 S rRNA sequencing were used to assess inflammation, intestinal barrier integrity, and gut microbiota (GM) composition. a Caco-2 cell-based model of UC was developed. After transfection to induce the overexpression of TLR4 and its adaptor protein MyD88, the cells were incubated with ISL. The effects of this intervention were evaluated by measuring the expression of inflammatory cytokines, tight junction-associated proteins, and components of the TLR4/MyD88 signaling pathway. ISL significantly alleviated DSS-induced UC symptoms, such as weight loss and colonic shortening. ISL reduced colonic mucosal damage and inflammatory cell infiltration, downregulated TLR4, MyD88, and phosphorylated NF-κB expression, and lowered TNF-α, IL-1β, and IL-6 levels. It also improved intestinal barrier function by upregulating ZO-1, Claudin-1, and Occludin expression. ISL modulated GM by increasing beneficial bacteria (Muribaculaceae) and reducing pathogenic bacteria (Escherichia-Shigella). Overexpression of TLR4 and MyD88 in the Caco-2 cell line abrogated the protective effects of ISL, as evidenced by increased expression of inflammatory cytokines and downregulated expression of tight junction proteins. Overall, these findings suggest ISL may protects against DSS-induced UC by suppressing the TLR4/MyD88/NF-κB pathway, enhancing intestinal barrier function, and modulating GM, supporting its potential as a therapeutic supplement for UC.
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Brain and Behavior
·
2026
·Vol. 16
·期 10
·e71773
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IF 2.8
Xin-ying Cai,Wen-jun Li,Cai-xia Chen,Lu Peng,Li-chao Yang,Xiao-ning Lin,Hong-tao Liu,Jian-bo Jia,Yan-chao Jiao,Ying Li
Background Glycyrrhizic acid (Gly-A) exhibits anti-inflammatory and antioxidant effects in various central nervous system disorders. Acute fatigue and chronic fatigue (CF) are associated with serious physical and psychological effects. However, the underlying pathophysiology and effective therapeutic strategies for these conditions remain poorly understood. Purpose This study aims to evaluate the therapeutic potential of Gly-A against fatigue, and to elucidate the underlying mechanisms of its action. Methods We established a mouse model of acute exercise-induced fatigue and evaluated fatigue-related indices. To identify specific pathways involved in Gly-A's therapeutic effects, we employed RNA sequencing, network pharmacology, and in vitro oxygen-deficit models, aiming to clarify the mechanisms. Additionally, we established a mouse model of CF to compare the therapeutic efficacy of Gly-A with positive control drugs by assessing identical parameters. Results Gly-A significantly improved fatigue-related indices without affecting body weight. RNA sequencing and network pharmacology analyses showed that Gly-A modulates oxidative stress responses and targets the NF-κB (nuclear factor-kappa B)/NLRP3 (NOD-like receptor thermal protein domain associated protein 3) signaling and apoptotic pathways. In the CF mouse model, oral administration of Gly-A significantly increased motor activity, alleviated anxiety and depression, and improved neurocognitive function compared to model mice, exhibiting superior efficacy to positive control drugs. These findings suggest that Gly-A exerts anti-inflammatory effects by targeting the NF-κB/NLRP3 signaling pathway, thereby reducing neuronal apoptosis in CF. Conclusions Gly-A exhibits therapeutic potential against acute exercise-fatigue and CF, primarily by attenuating apoptosis through the inhibition of the NF-κB/NLRP3 signaling pathway.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2026
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IF 6.6
Yangwei Xiang,Qin Wang,Ke Zhou,Weili Han
Phthalate esters (PAEs), widely used as plastic additives in consumer products such as food packaging, can be metabolized to phthalic acid (PTA) in vivo . However, the potential contribution of PTA to respiratory fibrotic processes remains poorly understood. In this study, we investigated the effects and underlying mechanisms of PTA on pulmonary fibrogenesis using human lung fibroblast IMR-90 cells chronically exposed to environmentally relevant concentrations of PTA (0–60 μg/L) for 14 days. PTA exposure promoted pro-fibrotic responses and cellular senescence, as evidenced by increased expression of fibrosis-associated markers, enhanced senescence-associated β-galactosidase activity, and upregulation of CDKN2A . Proteomic profiling and functional perturbation experiments further implicated the IL-1α/NF-κB/SASP signaling axis in these responses. PTA-induced senescence and pro-fibrotic effects were attenuated by inhibition of NF-κB signaling and IL-1 signaling, supporting the functional involvement of this pathway. In a bleomycin-induced progressive pulmonary fibrosis model, subsequent PTA exposure further aggravated collagen deposition and increased the pulmonary expression of fibrosis-, senescence-, and Il-1a/Nf-κb -associated genes, providing in vivo support for the biological relevance of the pathway identified in vitro . Molecular docking additionally predicted a potential interaction between PTA and IL-1α. Therefore, these findings offer novel mechanistic insights into environmental pollutant-induced fibrogenesis. Download: Download high-res image (131KB) Download: Download full-size image
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NEUROSCIENCE LETTERS
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2026
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IF 2.2
Qiang Zhang,Yilin Wang
Background Rheumatoid arthritis (RA) discomfort is linked to spinal cord microglia activation. Manual acupuncture (MA, twirling manipulation) reduces RA pain. MA’s ability to relieve RA discomfort was examined in this study. Methods After receiving complete Freund’s adjuvant (CFA), RA rats received acupuncture (with or without twisting manipulation). Paw withdrawal latency (PWL), nociceptive threshold, and hematoxylin and eosin (H&E) staining assessed arthritis severity. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to evaluate the levels of inflammatory factors (IL-1β, TNF-α and IL-6) in the spinal dorsal horn. Immunofluorescence was used to assess the expression of p-p38 and Iba-1 in the ipsilateral hippocampus and ipsilateral (right) dorsal root ganglia (DRG). Western blot was used to evaluate the expression of proteins linked to the nuclear factor kappa-B (NF-κB) /signal transducer and activator of transcription 3 (STAT3) pathway. Results MA treatment enhanced PWL, inhibited the expression of spinal dorsal horn inflammatory factor and the activation of ipsilateral DRG or ipsilateral hippocampal microglia, also down-regulated NF-κB/STAT3 pathway proteins. The effect of MA on RA symptoms was better than acupuncture alone. Conclusions Our findings demonstrate that MA significantly ameliorates pain in CFA-induced RA rats. The novelty of this study lies in identifying that this analgesic effect is achieved through the inhibition of the NF-κB/STAT3 signaling pathway, leading to a marked reduction in spinal microglia activation
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