JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Ma Tianyu,Li Qiang,Chen Xingwu,Dong Jixiang,Jiang Yuqing,Li Shanshan
Bioactive peptides are promising candidates for hair regeneration, but their topical application is often limited by poor skin delivery and the need for frequent dosing. To overcome these challenges, we designed a palmitoylated peptide, Pal-MPAPO, and incorporated it into a hyaluronic acid-based hydrogel microneedle (MN) system for localized transdermal delivery. The fabricated MNs showed adequate mechanical strength for skin insertion and provided a time-dependent, prolonged release of Pal-MPAPO. In human dermal papilla cells (DPCs), Pal-MPAPO activated the Wnt/β-catenin pathway and increased intracellular cyclic adenosine monophosphate (cAMP) levels in a predominantly VPAC1-dependent manner. Additional VPAC2 validation did not reveal a significant contribution to cAMP signaling under the tested conditions. Functional interactions between Pal-MPAPO and VPAC1 were supported by molecular docking, molecular dynamics simulations, receptor knockdown, and fluorescence imaging. In a C57BL/6 mouse model, Pal-MPAPO-loaded MNs significantly promoted hair regrowth, achieving efficacy comparable to minoxidil but at a reduced application frequency. These findings identify Pal-MPAPO as a potential peptide candidate for hair regeneration and suggest that hydrogel MN-assisted delivery provides a localized peptide administration strategy. Graphical The alternative text for this image may have been generated using AI.
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PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Xian Zheng,Yuanyue Jiang,Wenbo Wang,Kekang Sun,Libin Zhou,Yanru Zhang,Jie Cui,Haiyan Yu,Wenbin Dong,Baofei Yan
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, characterized by recurrent flare-ups and limited effectiveness of available drug therapies. Asiatic acid (AA), a triterpenoid compound extracted from Centella asiatica , has shown promising pharmacological activities and therapeutic potential in several inflammation-related diseases. However, AA's efficacy in treating UC and its precise mechanisms of action remain to be fully explored. This study aimed to provide a comprehensive assessment of AA's therapeutic effects on UC and to investigate its underlying mechanisms, with a focus on gut microbiota interactions. In our study, a dextran sulfate sodium-induced UC mouse model was used to evaluate AA's therapeutic potential and explore its impact on gut microbiota composition and function. We further used an antibiotic cocktail and fecal microbiota transplantation assays to substantiate the role of gut microbiota in AA's mechanisms of action. A metabolomic analysis was also conducted to identify key metabolic pathways and gut microbiota-derived metabolites involved in AA's effects. Our findings demonstrated that AA significantly alleviates symptoms of UC, including reducing weight loss, slowing disease progression, mitigating colonic inflammation, and restoring immune balance. Mechanistically, the beneficial effects of AA were strongly linked to alterations in the gut microbiota and its metabolites, particularly γ-glutamyltyrosine. This metabolite was found to regulate the cyclic adenosine monophosphate/protein kinase A/nuclear factor kappa-B signaling pathway, which plays a crucial role in inflammatory responses. Overall, these findings strongly suggest that AA holds promise as a therapeutic agent for UC by modulating the gut microbiota and influencing critical inflammatory pathways.
研究领域:
药理学
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胃肠病学
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微生物组研究
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炎症性疾病
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代谢组学
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PubMed
高影响因子
MOLECULAR PLANT PATHOLOGY
·
2024
·Vol. 25
·期 9
·e70003
·
IF 4.8
Kai Yin,Zhijian Hu,Meiting Yuan,Weidong Chen,Xinping Bi,Guobing Cui,Zhibin Liang,Yi Zhen Deng
Sugarcane smut fungus Sporisorium scitamineum produces polyamines putrescine (PUT), spermidine (SPD), and spermine (SPM) to regulate sexual mating/filamentous growth critical for pathogenicity. Besides de novo biosynthesis, intracellular levels of polyamines could also be modulated by oxidation. In this study, we identified two annotated polyamine oxidation enzymes (SsPAO and SsCuAO1) in S. scitamineum . Compared to the wild type ( MAT-1 ), the ss1pao Δ and ss1cuao1 Δ mutants were defective in sporidia growth, sexual mating/filamentation, and pathogenicity. The addition of a low concentration of cAMP (0.1 mM) could partially or fully restore filamentation of ss1pao Δ × ss2pao Δ or ss1cuao1 Δ × ss2cuao1 Δ. cAMP biosynthesis and hydrolysis genes were differentially expressed in the ss1pao Δ × ss2pao Δ or ss1cuao1 Δ × ss2cuao1 Δ cultures, further supporting that SsPAO- or SsCuAO1-based polyamine homeostasis regulates S. scitamineum filamentation by affecting the cAMP/PKA signalling pathway. During early infection, PUT promotes, while SPD inhibits, the accumulation of reactive oxygen species (ROS) in sugarcane, therefore modulating redox homeostasis at the smut fungus–sugarcane interface. Autophagy induction was found to be enhanced in the ss1pao Δ mutant and reduced in the ss1cuao1 Δ mutant. Exogenous addition of cAMP, PUT, SPD, or SPM at low concentration promoted autophagy activity under a non-inductive condition (rich medium), suggesting a cross-talk between polyamines and cAMP signalling in regulating autophagy in S. scitamineum . Overall, our work proves that SsPAO- and SsCuAO1-mediated intracellular polyamines affect intracellular redox balance and thus play a role in growth, sexual mating/filamentation, and pathogenicity of S. scitamineum .
研究领域:
真菌学
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植物病理学
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分子生物学
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PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-19
·
IF 12.6
Wang Lirui,Xiong Manyi,Zhang Jian,Li Sisi,Ma Sheng,Jiang Shengyao,Jiang Yanping,Li Xinhong
Introduction Preservation of porcine semen is essential for artificial insemination and genetic improvement in pig breeding programs. However, the overproduction of reactive oxygen species (ROS) and lower levels of protein phosphorylation emerge as two challenges during semen preservation. Inspired by the innate ligand-receptor binding biofunction of dopamine, herein, a dual-task nano-protectant that combines ROS-scavenging and protein phosphorylation-regulating properties via incorporating the natural antioxidant epigallocatechin gallate (EGCG) into polydopamine nanoparticles (EGCG@PDA NPs) was proposed to enhance the quality of pig semen during storage at 4 ℃. The results suggested that EGCG@PDA NPs significantly maintained sperm motility, acrosome integrity and mitochondrial membrane potential, extending semen storage time from 3 days to 10 days. Furthermore, EGCG@PDA NPs effectively scavenged excess ROS and inhibited ROS-mediated sperm apoptosis through the extracellular regulated protein kinases (ERK) signaling pathway. Intriguingly, EGCG@PDA NPs could degrade into ultrasmall particles (< 10 nm) in the semen or H 2 O 2 systems. These particles could target and activate the dopamine D2 receptor (D2DR) on membrane surface of sperm midpiece, thereby enhancing protein phosphorylation via the downstream cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling pathway, ultimately improving sperm motility parameters. This study presents a novel nano-strategy to boost the quality of pig semen, offering significant implications for the pig industry. Graphical
研究领域:
动物繁殖学
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生物化学
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分子生物学
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PubMed
高影响因子
Food Bioscience
·
2026
·
IF 6.2
Fenyi Min,Jiaqing Wang,Liping Qin,Yuxin Wang,Yizhou Li,Xuebo Liu,Lijun Sun
Plant-derived bioactive peptides have been suggested as a class of compounds with neuroprotective properties. This study focused on the cognitive-enhancing effects of Cyperus esculentus peptide (CEP) based on ‘in silico-drosophila-mice’ stepwise cognitive impairment models, followed by systematical elucidation in multi-target mechanism of its function. Specifically, network pharmacology prediction indicated that CEP exerted the modifying effects through essential nodes including cAMP signaling pathways and neuroinflammation regulation. Behavioral experiments confirmed that CEP effectively enhanced learning and memory capability of stress-modeled fruit flies and scopolamine-induced cognitive impairment mice. Then, mechanism investigation indicated that CEP could activate the cAMP-PKA-CREB-BDNF signaling axis within the central nervous system, enhancing synaptic plasticity (upregulated PSD-95 expression) while concurrently alleviating oxidative stress, cholinergic imbalance, and neuroinflammation. Additionally, CEP remodeled gut microbiota ecology, increasing beneficial bacteria abundance such as Akkermansia and Bifidobacterium and substantially enhancing short-chain fatty acid (SCFA) production. This further activated FFAR2/3 receptor signaling, restored intestinal barrier integrity and suppressed peripheral inflammation, indicating a neuroprotective pathway via the microbiota-gut-brain axis. Conclusively, this study confirmed CEP as a highly promising cognitive enhancer in a synergistic mode of coordinated regulation of central nervous and peripheral pathways, which provided theoretical underpinnings for intervention strategies of bioactive peptides in Cyperus esculentus targeting neurodegenerative diseases via the gut-brain axis.
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DOI
高影响因子
Journal of Animal Science and Biotechnology
·
2024
·Vol. 15
·期 1
·1-18
·
IF 6.3
Shang Lijun,Yang Fengjuan,Chen Qingyun,Dai Ziqi,Yang Guangxin,Zeng Xiangfang,Qiao Shiyan,Yu Haitao
Background The antibacterial and immunomodulatory activities of bacteriocins make them attractive targets for development as anti-infective drugs. Although the importance of the enteric nervous system (ENS) in the struggle against infections of the intestine has been demonstrated, whether it is involved in bacteriocins anti-infective mechanisms is poorly defined. Results Here, we demonstrated that the bacteriocin Microcin J25 (J25) significantly alleviated diarrhea and intestinal inflammation in piglets caused by enterotoxigenic Escherichia coli (ETEC) infection. Mechanistically, macrophage levels were significantly downregulated after J25 treatment, and this was replicated in a mouse model. Omics analysis and validation screening revealed that J25 treatment induced significant changes in the dopaminergic neuron pathway, but little change in microbial structure. The alleviation of inflammation may occur by down-regulating dopamine receptor (DR) D1 and the downstream DAG-PKC pathway, thus inhibiting arachidonic acid decomposition, and the inhibition of macrophages may occur through the up-regulation of DRD5 and the downstream cAMP-PKA pathway, thus inhibiting NF-κB. Conclusions Our studies’ findings provide insight into the changes and possible roles of the ENS in J25 treatment of ETEC infection, providing a more sophisticated foundational understanding for developing the application potential of J25.
研究领域:
微生物学
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免疫学
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神经科学
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药理学
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PubMed
高影响因子
Virulence
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2024
·
IF 5.5
Fen Wang,Jinping Zhang,Qian Zhang,Zhangyong Song,Caiyan Xin
Candida albicans is an opportunistic fungal pathogen that can cause systemic infections in immunocompromised individuals. Morphological transition and biofilm formation are major virulence factors of C. albicans. Moreover, biofilm enhances resistance to antifungal agents. Therefore, it is urgent to identify new and effective compounds to target the biofilm of C. albicans. In the present study, the antifungal activities of equol against C. albicans were investigated. In vitro, the microdilution analysis and spot assay result showed that equol exhibited potent inhibitory activities against C. albicans. Further investigations confirmed that the antifungal effects of equol involved interference with the transition from yeast to hypha and biofilm formation of C. albicans. In addition, transcriptome sequencing and reverse transcription-quantitative PCR (qRT-PCR) analysis showed that equol significantly downregulated the expression of several genes in the Ras1-cAMP-PKA pathway related to hyphae and biofilm formation and significantly upregulated the expression of the negative transcriptional repressors RFG1 and TUP1. Moreover, equol effectively reduced the production of cAMP, a key messenger in the Ras1-cAMP-PKA pathway, while supplementation with cAMP partly rescued the equol-induced defects in hyphal development. Furthermore, in a mouse model of systemic candidiasis (SC), equol treatment significantly decreased the fungal burden (liver, kidneys, and lung) in mice and local tissue damage, while enhancing the production of interleukin-10 (IL-10). Together, these findings confirm that equol is a potentially effective agent for treatment of SC.
研究领域:
微生物学
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药理学
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分子生物学
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传染病学
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PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Xiaoping Xie,Kexin Wang,Xiaoyan Shen,Xu li,Su Wang,Shun Yuan,Bowen Li,Zhiwei Wang
Microplastics (MPs) have attracted widespread attention because they can lead to combined toxicity by adsorbing heavy metals from the environment. Exposure to lead (Pb), a frequently adsorbed heavy metal by MPs, is common. In the current study, the coexistence of MPs and Pb was assessed in human samples. Then, mice were used as models to examine how co-exposure to MPs and Pb promotes aortic medial degeneration. The results showed that MPs and Pb co-exposure were detected in patients with aortic disease. In mice, MPs and Pb co-exposure promoted the damage of elastic fibers, loss of vascular smooth muscle cells (VSMCs), and release of inflammatory factors. In vitro cell models revealed that co-exposure to MPs and Pb induced excessive reactive oxygen species generation, impaired mitochondrial function, and triggered PANoptosome assembly in VSMCs. These events led to PANoptosis and inflammation through the cAMP/PKA-ROS signaling pathway. However, the use of the PKA activator 8-Br-cAMP or mitochondrial ROS scavenger Mito-TEMPO improved, mitochondrial function in VSMCs, reduced cell death, and inhibited inflammatory factor release. Taken together, the present study provided novel insights into the combined toxicity of MPs and Pb co-exposure on the aorta. Environmental Implication Microplastics (MPs) and Lead (Pb) are pervasive in the environment, yet studies on the cardiovascular toxicity of MPs and Pb co-exposure remain scarce. This research investigates the effects of MPs and Pb co-exposure on aortic medial degeneration (AMD). The findings reveal the presence of MPs and Pb exposure in patients. Co-exposure to MPs and Pb accelerates AMD in the mice. Further experiments confirm that co-exposure to MPs and Pb affects vascular smooth muscle cell activity and inflammation by regulating the cAMP/PKA pathway and mitochondrial function. Our study offers new insights into the synergistic toxic mechanisms of MPs and Pb.
研究领域:
环境科学
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毒理学
·
心血管疾病
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PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2021
·
IF 6.53
Baoyue Zhang,Jun Zhao,Pengfei Guo,Zhe Wang,Lvjie Xu,Ailin Liu,Guanhua Du
Naodesheng (NDS) tablets have been widely used to treat ischemic stroke clinically. NDS relieves neurological function impairment and improve learning and memory in rats with focal cerebral ischemia, suggesting that NDS has potential for Alzheimer’s disease (AD) treatment. However, there are no studies about its effective material basis and possible mechanisms. In this study, a systems pharmacology method was applied to reveal the potential molecular mechanism of NDS in the treatment of AD. First, we obtained 360 NDS candidate constituents through ADMET filter analysis. Then, 115 AD‐related targets were uncovered by pharmacophore model prediction via mapping the predicted targets against AD-related proteins. In addition, compound-target and target-function networks were established to suggest potential synergistic effects among the candidate constituents. Furthermore, potential targets regulated by NDS were integrated into AD-related pathways to demonstrate the therapeutic mechanism of NDS in AD treatment. Subsequently, a validation experiment proved the therapeutic effect of NDS on cognitive dysfunction in rats with intracerebroventricular injection of Aβ. We found that administration of NDS tablets regulates β-amyloid metabolism, improves synaptic plasticity, inhibits neuroinflammation and improves learning and memory function. In conclusion, this is the first study to provide a comprehensive systems pharmacology approach to elucidate the potential therapeutic mechanism of NDS tablets for AD treatment. We suggest that the protective effects of NDS in neurodegenerative conditions could be partly attributed to its role in improving synaptic plasticity and inhibiting neuroinflammation via NF-κB signaling pathway inhibition and cAMP/PKA/CREB signaling pathway activation.
研究领域:
药理学
·
神经科学
·
中医
·
系统生物学
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PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2023
·
IF 10.9
Jianmao Zheng,Jiyuan Zuo,Cairong Xiao,Qining Guo,Xiaobin Fu,Chengyun Ning,Peng Yu
The induction of dental pulp stem cells (DPSCs) into odontogenic differentiation is a cutting-edge method of dental pulp regeneration treatment. However, it remains a challenge to develop biomaterials and therapies that can induce odontogenic differentiation. Here, we propose a wireless electrical stimulation strategy to induce DPSCs odontogenic differentiation via K 0.5 Na 0.5 NbO 3 piezoelectric nanoparticles (KNN) and polarized KNN (PKNN), which can be endocytosed by DPSCs. In vitro, several odontogenic differentiation indexes were also increased in DPSCs treated with KNN and PKNN, and the increase was more obvious in the PKNN group. Intracellular wireless electrical field promoted mitochondrial calcium concentration via mitochondrial calcium unidirectional transporter (MCU), increased the production of adenosine triphosphate (ATP), and induced odontogenic differentiation through the activation of the cAMP-PKA signaling pathway. In vivo, dental pulp-like tissue was induced by electrical stimulation wirelessly with KNN and PKNN, which was more clinically friendly compared with the wired device, and the induction was more obvious in the PKNN group consistent with in vitro experiments. In conclusion, this work demonstrates the potential of PKNN as an effective stimulus that can induce odontogenic differentiation of DPSCs and be applied to dental pulp regeneration treatment.
研究领域:
牙科学
·
生物材料
·
干细胞生物学
·
纳米技术
·
再生医学
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DOI
高影响因子
EMBO Molecular Medicine
·
2025
·
IF 8.3
FengShengyong,MaEnhao,NaXiaona,WangZongmei,TaiWanbo,BaoXinhui,WangMao,ChangHan,WuBaolei,LiuMiaoxi,LiJuzhen,ShiHuicheng,YangCeli,XiMenglu,YangHaibing,LiYuhan,ZhuYibin,WangPenghua,ZhaoLing,ZhaoAi,ChengGong
Vaccination offers the most effective protection against contagious infectious diseases primarily by inducing humoral immunity. Vaccination efficacy is influenced by various factors. We report that dietary administration of arachidonic acid (ARA) significantly boosts rabies vaccine-induced production of neutralizing antibodies and protection against lethal rabies virus (RABV) infection in mice. In human volunteers, oral supplementation of ARA accelerates the expression of neutralizing antibodies to the levels sufficient for protection against RABV as early as one week after primary immunization. Mechanistically, ARA is enriched in lymph nodes and metabolized into immune modulators there. One of the ARA metabolites, prostaglandin I2 (PGI2), via the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) axis, upregulates the expression of costimulatory molecule CD86, and activates activation-induced cytidine deaminase (AID) in B cells. These results suggest that ARA can be a potent dietary adjuvant to foster germinal center (GC) B cell response and humoral immunity.
研究领域:
免疫学
·
营养科学
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病毒学
·
疫苗研究
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DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2016
·
IF 4.191
Wenjun Zhao,Aiyun Li,Xin Feng,Ting Hou,Kang Liu,Baolin Liu,Ning Zhang
This study aims to investigate the effects of metformin and resveratrol on muscle insulin resistance with emphasis on the regulation of lipolysis in hypoxic adipose tissue. ICR mice were fed with high fat diet (HFD) for 10 days with administration of metformin, resveratrol, or intraperitoneal injection of digoxin . Adipose hypoxia, inflammation and cAMP/PKA-dependent lipolysis were investigated. Moreover, lipid deposition and insulin resistance were examined in the muscle. Metformin and resveratrol attenuated adipose hypoxia, inhibited HIF-1α expression and inflammation in the adipose tissue of HFD-fed mice. Metformin and resveratrol inhibited lipolysis through prevention of PKA/HSL activation by decreasing the accumulation of cAMP via preserving PDE3B . Metformin and resveratrol reduced FFAs influx and DAG accumulation, and thus improved insulin signaling in the muscle by inhibiting PKCθ translocation. This study presents a new view of regulating lipid metabolism to ameliorate insulin resistance and provides the clinical guiding significance for obesity and type 2 diabetes with metformin and resveratrol treatment.
研究领域:
药理学
·
内分泌学
·
代谢学
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DOI
PubMed
高影响因子
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