CARBOHYDRATE POLYMERS
·
2025
·
IF 12.5
Yang Yang,Gengyu Zhou,Yang Chen,Ning Lin,Jingzhi Ma
Diabetic periodontitis, characterized by persistent inflammation and impaired periodontal tissue regeneration under hyperglycemic conditions, urgently requires innovative therapeutic strategies. Microneedle (MN) technique has recently emerged as a promising solution for diabetic periodontitis by enabling minimally invasive and localized drug delivery. In this study, we developed poly(lactic acid) (PLA)-based MNs reinforced with PLA-grafted tunicate cellulose nanocrystals (TCNC-g-PLA@PLA-MNs), demonstrating favorable mechanical strength and biocompatibility. After loading with irisin and interleukin-1 (IL-1) receptor antagonist (IL-1ra) via surface polydopamine functionalization, the MNs exhibited anti-inflammatory effects by markedly reducing the expressions of IL-6 by 0.53-fold, IL-8 by 0.23-fold, and MCP-1 by 0.41-fold in human periodontal ligament cells (hPDLCs). Additionally, they significantly promoted osteogenic differentiation, increasing the expressions of ALP by 1.87-fold, OPN by 2.21-fold, OCN by 1.39-fold, and Runx2 by 2.28-fold, which was further supported by enhanced ALP staining. Furthermore, the MNs improved the migration ability of hPDLCs under inflammatory and high-glucose culture conditions. Our findings highlight that the TCNC-g-PLA@PLA-MNs effectively integrate structural reinforcement and therapeutic functionality, providing a novel and potential platform to promote periodontal regeneration in the context of diabetic periodontitis.
研究领域:
生物材料学
·
口腔医学
·
药剂学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6
Zi-Qiang Feng,Jing Ding,Min-Zhen Zhu,Wei-Song Xie,Rui-Chen Liu,Si-Si Liu,Si-Meng Liu,Ming-Jia Yu,Xin-Hong Zhu,Jian-Hua Liang
Recently, some inhibitors of soluble epoxide hydrolase (sEH) showed limited potential in treating sepsis by increasing survival time, but they have unfortunately failed to improve survival rates. In this study, we initially identified a new hit 11D , belonging to a natural skeleton known as stilbene and having an IC 50 of 644 nM on inhibiting murine sEH. Natural scaffold-based sEH inhibitors are paid less attention. A combination of structure-activity relationships (SARs)-guided structural optimization and computer-aided skeleton growth led to a highly effective lead compound 70P (IC 50 : 4.0 nM). The dose-response study indicated that 70P (at doses of 0.5–5 mg/kg, ip.) significantly increased survival rates and survival time by reducing the levels of the inflammatory factors TNF-α and IL-6 in the liver. Interestingly, 70P exhibited much higher accumulation in the liver than in plasma (AUC ratio: 175). In addition, 70P exhibits equal IC50 value (1.5 nM) on inhibiting human sEH as EC5026 (1.7 nM). In conclusion, the natural scaffold-extended sEH inhibitor 70P has the potential to become a new promising lead for addressing the unmet medical need in sepsis treatment, which highlighted the importance of natural skeleton in developing sEH inhibitors.
研究领域:
药理学
·
医学
·
计算化学
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DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Henggang Wang,Shan Sun,Ye Zhao,Peng Wang,Yonghua Zhou,Haoyi Sun,Jin Yang,Ke Cheng,Si Li,Hengwei Lin
Diabetic wounds pose a persistent challenge due to their slow healing nature, primarily caused by bacterial infection and excessive reactive oxygen species (ROS)-induced inflammation. In this study, carbon dots with synergistic antibacterial and antioxidant properties, referred to as AA-CDs, are developed specifically for diabetic wound healing using a straightforward solvothermal method. By utilizing cost-effective precursors like citric acid and ascorbic acid, AA-CDs are engineered to possess tailored functions of photothermal sterilization and ROS scavenging. The resulting AA-CDs demonstrats broad-spectrum antibacterial activity, particularly against multidrug-resistant strains, along with efficient ROS scavenging both in solution and within cells. Additionally, AA-CDs exhibits a protective effect against oxidative stress-induced damage. Notably, with a high photothermal conversion efficiency (41.18%), AA-CDs displays heat-enhanced antioxidant performance, providing not only augmented ROS scavenging but also additional protection against oxidative stress, yielding a true “1 + 1 > 2” effect. To facilitate their use in vivo, AA-CDs are incorporated into a thermally responsive hydrogel, which exhibits evident anti-inflammatory properties by modulating inflammatory factors and significantly promots the healing of diabetic wounds. This study underscores the value of integrated platforms for diabetic wound healing and highlights the potential of versatile CDs as promising therapeutic agents in biomedical applications.
研究领域:
纳米技术
·
生物医学工程
·
材料科学
·
药学
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DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2024
·
IF 8
Deying Zou,Jiang Chang,Shiying Lu,Pan Hu,Kai Zhang,Cheng Han,Feng Li,Yansong Li,Dan Chi,Mengyan Cheng,Jianfeng Xu,Xiaoli Sun,Zengshan Liu,Honglin Ren
Brucellosis is a worldwide zoonoses posing a significant threat to humans and animals. The difficulty in distinguishing between Brucella infection and vaccination has led to substantial health risks and economic losses. In this study, we developed a fluorescent dual-signal immunosensor, integrating it with machine learning to solve this problem. Immunogens were selected through structural analysis, followed by the screening of monoclonal antibodies. The antibodies were conjugated with fluorescent microspheres, serving as immunoprobes. Employing a dual-antibody sandwich strategy, we prepared the immunosensor and utilized machine learning to analyze the correlation between multibiomarkers and the status of Brucella infection or vaccine-induced immunity. The immunosensor achieved detection limits of 7.56 pg/mL for IL-1β and 76.61 pg/mL for IL-1Ra, without cross-reactivity with common inflammatory factors. Utilizing the Random Forest algorithm, the combination of the IL-1Ra/IL-1β ratio and RBPT achieved a F1 score of 1.0. Overall, the strategy effectively distinguishes between Brucella -infected and vaccinated subjects, offering valuable applications for brucellosis monitoring.
研究领域:
医学诊断
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免疫学
·
生物信息学
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产品关联
DOI
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Wenjie Xi,Weijie Wu,Lili Zhou,Qi Zhang,Shushu Yang,Lihong Huang,Yijun Lu,Jing Wang,Xinjin Chi,Yang Kang
Sepsis is a serious and life-threatening condition, which can lead to organ failure and death clinically. Abnormally increased cell-free DNA (cfDNA) and inflammatory cytokines are involved in the development and progression of sepsis. Thus, cfDNA clearance and down-regulation of inflammatory factors are essential for the effective treatment of sepsis. Here we designed and constructed a polydopamine-based multifunctional nanoparticle for the treatment of sepsis. These nanoparticles (NPs) are composed of polydopamine (PDA) grafted with cationic polyethyleneimine (PEI). On the one hand, the NPs can utilize the electrostatic interaction to effectively adsorb cfDNA in blood, then effectively inhibiting the activation of toll like receptors (TLRs) and nuclear factor kappa B (NF-κB) pathways induced by cfDNA. On the other hand, the NPs have an immunomodulatory function, which can effectively convert pro-inflammatory macrophage (M1) into anti-inflammatory macrophage (M2), thus reduce the release of inflammatory cytokines and slow down the inflammatory storm of sepsis. In addition, the NPs possess good reactive oxygen species (ROS) scavenging ability. Briefly, the effective treatment of sepsis can be achieved by multiple strategies of effectively capturing the inflammatory triggering factor cfDNA, modulating the polarization of M1 macrophage to M2 macrophage and scavenging ROS, which has a promising clinical application.
研究领域:
医学
·
免疫学
·
纳米医学
·
感染与炎症
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Chen Jiayun,Jiang Xiaojuan,Zhu Chunyan,Yang Lu,Liu Minting,Zhu Mingshe,Wu Caisheng
Rhubarb, as a traditional Chinese medicine, has several positive therapeutic effects, such as purging and attacking accumulation, clearing heat and purging fire, cooling blood, and detoxification. Recently, Rhubarb has been used in prescriptions for the prevention and treatment of COVID-19, with good efficacy. However, the exploration of effective quantitative approach to ensure the consistency of rhubarb’s therapeutic efficacy remains a challenge. In this case, this study aims to use non-targeted and targeted data mining technologies for its exploration and has comprehensively identified 72 rhubarb-related components in human plasma for the first time. In details, the area under the time-concentration curve (AUC)-pooled method was used to quickly screen the components with high exposure, and the main components were analyzed using Pearson correlation and other statistical analyses. Interestingly, the prototype component (rhein) with high exposure could be selected out as a Q-marker, which could also reflect the metabolic status changes of rhubarb anthraquinone in human. Furthermore, after comparing the metabolism of different species, mice were selected as model animals to verify the pharmacodynamics of rhein. The in vivo experimental results showed that rhein has a positive therapeutic effect on pneumonia, significantly reducing the concentration of pro-inflammatory factors [interleukin (IL)-6 and IL-1β] and improving lung disease. In short, based on the perspective of human exposure, this study comprehensively used intelligent data post-processing technologies and the AUC-pooled method to establish that rhein can be chosen as a Q-marker for rhubarb, whose content needs to be monitored individually.
研究领域:
中药学
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药理学
·
数据挖掘
·
代谢
·
炎症
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Sheng Chen,Enen Chen,Xiaoling Guan,Junfang Li,Aiping Qin,Chen Wang,Xihua Fu,Chen Huang,Jianhao Li,Yukuan Tang,Minyan Wei,Lingmin Zhang,Jianfen Su
Cytokine storms characterized by excessive secretion of circulating cytokines and immune-cell hyperactivation are life-threatening systemic inflammatory syndromes. The new strategy is in great demand to inhibit the cytokine storm. Here, we designed a type of magnetically controlled nanorobots (MAGICIAN) by fusing neutrophil membranes onto Fe 3 O 4 nanoparticles (Fe 3 O 4 NPs). In our study, the receptors of neutrophil membranes were successfully coated to the surface of Fe 3 O 4 NPs. The associated membrane functions of neutrophils were highly preserved. MAGICIAN could in vitro neutralize the inflammatory cytokines including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ). Interestingly, MAGICIAN could be navigated to the liver sites under magnetic control and accelerated the cytokine clearance by the liver. Administration of MAGICIAN could efficiently relieve the inflammation in the acute lung injury mouse model. In addition, MAGICIAN displayed good biosafety in systemic administration. The present study provides a safe and convenient approach for the clearance of cytokine storms, indicating the potential for clinical application in acute lung injury therapy.
研究领域:
医学
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生物工程
·
免疫学
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产品关联
DOI
PubMed
高影响因子
Foods
·
2025
·Vol. 14
·期 19
·3396
·
IF 5.1
Shoucheng Pu,Jufang Gong,Meihao Sun,Zunhong Hu,Zhihua Wu
Polygonatum cyrtonema Hua, a plant with a long history of consumption in China, serves both medicinal and edible purposes, and it exhibits numerous pharmacological effects, including promoting kidney health and enhancing immune function. However, the effect and molecular mechanism of Polygonatum cyrtonema polysaccharides (PCPs) on hyperuricemia have not yet been reported. The hyperuricemic mice model was induced by the intraperitoneal injection of potassium oxonate (PO, 300 mg/kg), combined with the intragastric administration of hypoxanthine (HX, 300 mg/kg). Biochemical assays in mice revealed that PCPs markedly lowered high serum uric acid levels, suppressed xanthine oxidase (XOD) activity, and reduced the expression of inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Western blot analysis demonstrated that PCPs downregulated urate transporter 1 (URAT1), while H&E staining showed that PCPs effectively restored renal histological integrity. Here, we isolated and identified the PCPs, which consist mainly of rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose, with a molar mass ratio of 0.5:2.15:0.47:16.58:3.66:1.09. Furthermore, the galactose residue that docked with both XOD and URAT1 molecules forms more hydrogen bonds and exhibits a lower binding energy, which enables the improved regulation of both targets. We have demonstrated for the first time the improving effect of PCPs on hyperuricemia, and revealed their regulatory mechanisms by modulating xanthine oxidase, inflammatory factors, and uric acid transporters. This study not only provides new insights into the anti-hyperuricemic activity of PCPs in mice, but also lays a foundation for its potential application in the functional foods of anti-hyperuricemia.
研究领域:
药理学
·
分子生物学
·
代谢性疾病
·
天然产物化学
·
肾脏病学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Shengchen Ding,Jun Chen,Guangming Chen,Weiyi Tian,Junping Zheng,Haiming Hu,Lu Cao,Xiaowei Yao,Baifei Hu,Hongtao Liu
This study aimed to isolate oligosaccharides from P. sibiricum , analyze its structure, and elucidate the pharmacological mechanism for colitis improvement. First, a homogeneous oligosaccharide PSO-A was isolated and its structure was characterized. Then, the colitis model was induced with 3 % dextran sulfate sodium (DSS) and intervened with PSO-A. The results show that PSO-A was an agavin-type acetylated fructooligosaccharide with a molecular weight of 2.12 kDa. PSO-A consisted of (2 → 6)-β-D-Fru f residue backbone with an internal α-D-Glc p residue and (2 → 1)-β-D-Fru f residue side chains. Further, PSO-A increased mucin content, protected intestinal barrier integrity of colitis mice, and significantly inhibited the levels of inflammatory factors. Moreover, the protein expressions of NLRP3, ASC, and Caspase-1 in colitis mice was statistically inhibited by PSO-A. In summary, PSO-A could alleviate colitis by inhibiting NLRP3 inflammasome pathway, which provides a basis for the development and application of P. sibiricum oligosaccharides as drug or functional food to relieve colitis.
研究领域:
药理学
·
生物化学
·
分子生物学
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免疫学
·
胃肠病学
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产品关联
DOI
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2021
·Vol. 44
·期 8
·1093-1100
·
IF 2.233
Chang Xu,Man Zhang,Guangping Zhang,Sheng Yan,Weiqi Yan
Hydrogen sulfide (H2S), an important gaseous messenger, is known to have neuroprotective effects in many neurological disorders. This study examined the neuroprotective effects and the associated mechanisms of H2S in the model Sprague–Dawley (SD) rats with spinal cord injury (SCI). We found that H2S showed neuroprotective effects in SCI model rats, improved the symptoms of neurological impairment, reduced the secretion of inflammatory factors, nerve cell apoptosis, and endoplasmic reticulum (ER), and oxidative stresses. Moreover, these effects were produced by activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) protein. Our results suggest that H2S supplementation could be a potential therapeutic strategy to promote SCI recovery.
研究领域:
神经科学
·
药理学
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DOI
PubMed
高影响因子
TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH
·
2022
·Vol. 21
·期 10
·2139-2146
·
IF 0.523
Limei Du,Xinglan Huo,Ying Liu
Purpose: To study the influence of resveratrol on chronic obstruction in Aspergillus fumigatus infection-induced chronic lung disease (COPD) in rats, and the process involved.
Methods: Seventy-five Sprague Dawley SD) rats were assigned to blank control, COPD model, Aspergillus fumigatus-infected COPD model, low (100 mg/kg) and high-dose (200 mg/kg) resveratrol groups, with 15 rats in each group. Enzyme-linked immunosorbent assay (ELISA) was used to assay IL-6, IL-8 and TNF-α in bronchoalveolar lavage fluid (BALF), while lung protein concentrations of AMPK and PGC-1α were assayed by immunoblotting.
Results: In low- and high-dose resveratrol groups, inflammatory factor levels were significantly lower than the corresponding levels in COPD model and Aspergillus fumigatus-infected COPD model (p < 0.05), while lung tissue proteins of AMPK, PGC-1α, and AQP5 of the rats given high-dose resveratrol were significantly raised, relative to corresponding levels in rats given low-dose resveratrol (p < 0.05).
Conclusion: Resveratrol modulates expression levels of secretory factors and surface markers in alveolar macrophages in COPD model rats infected with Aspergillus fumigatus. Resveratrol exerts this effect through the regulation of AMPK/PGC-1α signaling pathway.
研究领域:
药理学
·
免疫学
·
呼吸医学
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产品关联
DOI
高影响因子
Food & Function
·
2025
·
IF 5.4
Yuhui Ye,Xiaoyi Jiang,Yijun Jiang,Longteng Zhang,Binsong Han,Yulong Wang,Pengyan Liu,Xin Lu,Cun-Zheng Zhang
Although often regarded as compromising the fruit’s sensory quality, pear peel is an edible component that enhances the nutritional and functional value of pears within a whole food diet. Rich in diverse polyphenols with demonstrated bioactivity, the pear peel represents a valuable dietary source of health-promoting compounds, however, its role in ulcerative colitis (UC) remains underexplored. In this study, the protective effect of pear peel polyphenols (PPP) against UC was investigated using both in vitro and in vivo models. PPP markedly suppressed proinflammatory cytokine and enzyme expressions in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages. In dextran sulfate sodium (DSS) induced colitis mice, PPP significantly mitigated UC symptoms, suppressed serum inflammatory cytokine production, and ameliorated histological damage in colon tissues. Moreover, PPP modulated the gut microbiota by reshaping microbial diversity, enriching beneficial taxa such as Akkermansia, and suppressing proinflammatory taxa including Bacteroides, Enterobacteriaceae, and Parabacteroides. Proteomic analysis further demonstrated that PPP modulated mucosal immunity, particularly by rebalancing immunoglobulin-related processes (IgM, IgD, and IgA) and attenuating antigen presentation responses involving major histocompatibility complex (MHC) class II molecules and cluster of differentiation (Cd40) signaling. Together, these findings suggest that PPP exerts a protective effect against colitis through the coordinated regulation of gut microbiota and mucosal immunity, highlighting its potential as a functional food ingredient for intestinal health.
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产品关联
DOI
PubMed
高影响因子
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