SAUDI PHARMACEUTICAL JOURNAL
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2020
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IF 2.879
Qing Wang,Di Zhuang,Wenchang Feng,Bitao Ma,Liping Qin,Lilun Jin
Osteoarthritis (OA) is a disease characterized by degeneration of the joint complex due to cartilage destruction. Fraxetin, a widely used and studied coumarin compound extracted from a traditional Chinese herb (Qin Pi), has shown anti-inflammatory and antioxidant properties, but its effects on OA have not been studied. In the present study, western blotting, immunofluorescence, and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) were used to evaluate the effects of fraxetin on IL-1β-induced apoptotic activity, inflammatory responses, and catabolism in rat chondrocytes. The results showed that fraxetin prevented IL-1β-induced apoptosis of chondrocytes and inhibited inflammatory mediator release by regulating the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor (NF)-κB pathway in chondrocytes. Additionally, fraxetin suppressed the upregulation of matrix metalloproteinase 13 (MMP13) and degradation of collagen II in the extracellular matrix (ECM). Moreover, the effects of fraxetin in vivo were assessed in a monosodium iodoacetate (MIA)-induced rat model of OA using hematoxylin and eosin (H&E) and Safranin O-fast green staining and magnetic resonance imaging (MRI). The results showed that fraxetin protected the cartilage against destruction. In conclusion, fraxetin could be a potential therapeutic for OA.
研究领域:
药理学
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风湿病学
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骨科
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产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
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2023
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IF 7.2
Waimei Si,Xin Li,Bei Jing,Shiquan Chang,Yachun Zheng,Zhenni Chen,Guoping Zhao,Di Zhang
(Switching from the microglial M1 phenotype to the M2 phenotype is a promising therapeutic strategy for neuropathic pain (NP). This study aimed to investigate the potential use of stigmasterol for treating NP. In animal experiments, 32 male Sprague–Dawley rats were randomly divided into the sham operation group, chronic constriction injury (CCI) group, CCI + ibuprofen group, and CCI + stigmasterol group. We performed behavioral tests, enzyme-linked immunosorbent assay, hematoxylin-esoin staining (H&E) staining and immunohistochemistry, immunofluorescence, and Western blotting. In cell experiments, we performed flow cytometry, immunofluorescence, Western blotting, and qRT-PCR. Stigmasterol reduced thermal and mechanical hyperalgesia and serum IL-1β and IL-8 levels and increased serum IL-4 and TGF-β levels in CCI rats. Stigmasterol reduced IL-1β, COX-2, and TLR4 expression in the right sciatic nerve and IL-1β expression in the spinal cord. Stigmasterol reduced the expression of Iba-1, TLR4, MyD88, pNF-κB, pP38 MAPK, pJNK, pERK, COX-2, IL-1β, and CD32 in the spinal cord of CCI rats while increasing the expression of IL-10 and CD206. Stigmasterol decreased M1 polarization markers and increased M2 polarization markers in lipopolysaccharide (LPS)-induced microglia and decreased the expression of Iba-1, TLR4, MyD88, pNF-κB, pP38 MAPK, pJNK, pERK, iNOS, COX-2, and IL-1β in LPS-treated microglia while increasing the expression of Arg-1 and IL-10. Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF-κB pathway to alleviate NP.
研究领域:
药理学
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神经科学
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免疫学
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疼痛研究
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Xiaoyu Wu,Chuanbo Ding,Xinglong Liu,Qiteng Ding,Shuai Zhang,Yue Wang,Chenran Xin,Hewei Wei,Rui Mao,Guiping Zhang,Ting Zhao,Wencong Liu
Wound healing in diabetic patients is often complicated by issues like inflammation, infection, bleeding, and fluid retention. To tackle these challenges, it is essential to create hydrogel dressings with anti-inflammatory, antibacterial, and antioxidative properties. This study aimed to synthesize Phlorizin-Liposomes (PL) through the thin-film dispersion method and integrate them into an oxidized sodium alginate (OSA) and carboxymethyl chitosan (CMCS) hydrogel scaffold, resulting in an OSA/CMCS/PL (PLOCS) composite hydrogel via a Schiff base reaction. Characterization of the composite was performed using FTIR, TEM, and SEM techniques. The research assessed the swelling behavior, antibacterial effectiveness, and biocompatibility of the PLOCS composite hydrogel, while also investigating how PLOCS facilitates diabetic wound healing. The results demonstrated that PLOCS effectively controls drug release, possesses favorable swelling and degradation characteristics, and shows significant antioxidative properties along with in vitro biocompatibility. Histological analysis confirmed that PLOCS supports the proliferation of healthy epithelial tissue and collagen production. Western blotting indicated that PLOCS diminishes inflammation by inhibiting the TLR4/NF-κB/MyD88 pathway and activates Nrf2 to boost wound healing, increasing the levels of antioxidative enzymes such as HO-1, NQO1, and GCLC. In summary, PLOCS presents a promising new option for advanced wound dressings aimed at treating diabetic ulcers.
研究领域:
材料科学
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生物医学工程
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药剂学
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伤口愈合
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糖尿病
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产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
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2022
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IF 0
Shuwen Sun,Chuanbo Ding,Xinglong Liu,Yingchun Zhao,Jinping Zhang,Qiteng Ding,Yiwen Zhang,Yue Zhang,Mingqian Hao,Yinan Zheng,Wencong Liu,Min Yang
In modern clinical applications, wound healing remains a considerable challenge. Excessive inflammatory response is associated with delayed wound healing. In this study, we prepared composite nanofibrous membranes by mixing the Chinese herbal extract puerarin (PUE) with natural silk protein (SF) and synthetic polymer polyvinylpyrrolidone (PVP) using electrostatic spinning technique, and conducted a series of studies on the structural and biological properties of the fibrous membranes. The results showed that the loading of PUE increased the diameter, porosity and hydrophilicity of nanofibers, which were more favorable for cell adhesion and proliferation. ABTS radical scavenging assay also showed that the loading of PUE enhanced the antioxidant properties of the fibrous membranes. In addition, SF/PVP/PUE nanofibers are non-toxic and can be used as wound dressings. In vitro experiments showed that SF/PVP/PUE nanofibers could effectively alleviate lipopolysaccharide (LPS)-induced inflammation in Immortalized human keratinocytes (HaCaT) cells and down-regulate pro-inflammatory cytokine expression in cells. In vivo studies further showed that the SF/PVP/PUE nanofibers could effectively accelerate wound repair. The mechanism is that SF/PVP/PUE nanofibers can inhibit the activation and transduction of toll-like receptor 4/myeloid differentiation factor88/nuclear factor kappa B (TLR4/MyD88/NF-κB) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathways, thereby reducing the inflammatory response and achieving wound healing.
研究领域:
生物医学工程
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药学
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材料科学
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细胞生物学
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伤口愈合
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产品关联
DOI
PubMed
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2018
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IF 3.909
Song-Tao Fan,Shao-Ping Nie,Xiao-Jun Huang,Sunan Wang,Jie-Lun Hu,Jun-Hua Xie,Qi-Xing Nie,Ming-Yong Xie
In vivo an ecological network of polysaccharides utilization by gut microbiota is not only an intense competition but also an impressive cooperation pattern. The present study evaluated the in vivo protective effect of combined fungal polysaccharides (CFP) from Cordyceps sinensis and Ganoderma atrum on colon immune dysfunction, induced by 150 mg/kg cyclophosphamide (CP). The results showed that C. sinensis polysaccharides (CSP) significantly promoted microbial-derived butyrate to improve histone h3 acetylation mediating regulatory T (Treg) cell specific Foxp3, as well as significantly restored CP-induced elevation of interleukin (IL)-17 and IL-21. Additionally, G. atrum polysaccharides (PSG) significantly down-regulated MyD88, as well as significantly increased IL-10 and TGF-β3. Furthermore, CFP balanced the disequilibrium of cytokines secretion and Foxp3/RORγt ratio related Treg/T helper 17 (Th17) balance, as well as down-regulated the TLR-mediated inflammatory signaling pathway and promoted secretory immunoglobulin A (sIgA) secretion to suppress colonic inflammation. Therefore, our results typically contribute to understand the in vivo immunoregulatory function of fungal polysaccharides compounds, involving microbial-associated inflammatory signals and specific metabolic products.
研究领域:
免疫学
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药理学
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微生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Hongping Wan,Kai Deng,Zhengqun Huang,Yunhan Yang,Bo Jing,Yumei Feng,Yuanfeng Li,Yong Liu,Mingqin Lu,Xinghong Zhao
Despite the safety profile of subunit vaccines, the inferior immunogenicity hinders their application in the nasal cavity. This study introduces a novel antigen delivery and adjuvant system utilizing mucoadhesive chitosan–catechol (Chic) on silica spiky nanoparticles (Ssp) to enhance immunity through multiple mechanisms. The Chic functionalizes the Ssp surface and incorporates with SARS-CoV-2 spike protein receptor-binding domain (RBD) and toll-like receptor (TLR)9 agonist unmethylated cytosine-guanine (CpG) motif, forming uniform virus-like nanoparticles (Ssp-Chic-RBD-CpG) via electrostatic and covalent interactions. Ssp-Chic-RBD-CpG, mimicking the morphology and function of inactive virions, effectively prolongs the retention time of RBD in the nasal mucosa by 3.92-fold compared to RBD alone, enhances the maturation of dendritic cells (DCs), and facilitates the antigen trafficking to the draining lymph nodes, which subsequently induces a stronger mucosal immunity. Mechanistically, the enhanced chemokine chemokine (C-C motif) ligand 20 (CCL20)-driven DCs recruitment and maturation by Ssp-Chic-RBD-CpG are evidenced by a cell co-culture model. In addition, the overexpression of TLR4/9 and activation of MYD88/NF-κB signaling pathway in activation of DCs are observed. Proof of principle is obtained for RBD, but similar delivery mechanisms can be applied in other protein-based subunit vaccines as well when intranasal administration is needed.
研究领域:
纳米技术
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免疫学
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疫苗开发
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分子生物学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2018
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IF 2.559
Fan Zhang,Chenhong Zhang
Intracerebral hemorrhage (ICH) is reported as a common and often fatal type of stroke accompanied with high morbidity and mortality, and it frequently results in long-lasting neurological dysfunctions. However, the pathogenesis that contributes to ICH has not been fully understood. Rnf112, also known as Znf179, is a member of the RING finger protein family. The expression of Rnf112 is abundant in the brain and is modulated during brain progression and development. The study aimed to explore the role of Rnf112 in brain injury after ICH, as well as the underlying molecular mechanisms. The results indicated that ICH led to a significant decrease in Rnf112, which was confirmed in oxyhemoglobin (oxyHb)-incubated astrocytes and microglial cells. Moreover, the Rnf112 knockout (Rnf112 −/− ) mice and wild type (WT) mice induced by ICH were further employed. Compared to the WT/ICH group, Rnf112 −/− mice exhibited accelerated brain injury, as evidenced by the increased brain water contents and neurological deficit scores (NDS). In comparison to WT/ICH group, a remarkable up-regulation in the release of pro-inflammatory cytokines, including tumor necrotic factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, was observed in perihematoma tissues of Rnf112 −/− mice on day 3 post-ICH. The process was along with promoted glial fibrillary acidic protein (GFAP) and Iba1 expression and reduced NeuN levels. Furthermore, ICH-induced increases in toll-like receptor (TLR)-4 and myeloid differentiation primary response protein (MyD88) expression were exacerbated by the loss of Rnf112. The phosphorylated expression of IKKα, inhibitor of NF-κB (IκBα) and nuclear factor-kappa B (NF-κB) induced by ICH in perihematoma tissues of mice was markedly enhanced in Rnf112 −/− mice. Rnf112 repression-induced inflammatory response was verified in lipopolysaccharide (LPS)-incubated glial cells . In contrast, over-expressing Rnf112 markedly attenuated ICH-induced brain injury by restraining inflammation via inactivating TLR-4/NF-κB pathway. In summary, our findings suggested that Rnf112 expression was highly involved in the progression of ICH, and targeting Rnf112 signaling might be a promising therapeutic strategy against ICH development.
研究领域:
神经科学
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分子生物学
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病理学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Yuan Chen,Yi Zhou,Jinhan Cai,Jiayi Xu,Chenwei Hu,Huiyue Chen,Yirui Hong,Nanyi Pan,Yujie Jiang,Chenhui Zhou,Hua Wei,Zhipeng Xu,Lin Liu,Xiang Wu,Wei Cui
Post-operative cognitive dysfunction (POCD) is a multi-etiological symptom mainly occurred in elderly people after surgery. The activation of retinoic acid receptor α (RARα), a transcriptional factor, was previously predicated to be negatively associated with the occurrence of POCD. However, the mechanisms underlying anti-POCD effects of RARα were still unclear. In this study, AM580, a selective agonist of RARα, and all-trans-retinoic acid (ATRA), a pan agonist of RAR, significantly alleviated cognitive dysfunction and increased the expression of RARα in elderly mice after surgery, which was decreased by RO41-5253, an antagonist of RARα. A bioinformatic study further predicted that the activation of RARα might produce anti-POCD effects via the restoration of synaptic proteins. Both agonists inhibited the expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88) and the phosphorylation of nuclear factor kappa-B (NF-κB), leading to the prevention of microglial over-activation and pro-inflammatory cytokines secretion in the hippocampal regions of elderly mice after surgery. Moreover, AM580 and ATRA increased the expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95), and the phosphorylation of extracellular signal-regulated kinase (ERK) and cAMP-response element binding protein (CREB). All these results suggested that the activation of RARα prevented surgery-induced cognitive impairments via the inhibition of neuroinflammation by the reduction of the TLR4/Myd88/NF-κB pathway and the restoration of synaptic proteins by the activation of the BDNF/ERK/CREB pathway, providing a further support that RARα could be developed as a therapeutic target for POCD.
研究领域:
神经科学
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药理学
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老年医学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
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2024
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IF 5.1
Fenfen Wei,Huibin Jiang,Chuang Zhu,Lingyue Zhong,Zihan Lin,Yan Wu,Lihua Song
A high-fat diet (HFD) is associated with various adverse health outcomes, including cognitive impairment and an elevated risk of neurodegenerative conditions. This relationship is partially attributed to the influence of an HFD on the gut microbiota. The objective of this research was to evaluate the neuroprotective benefits of co-fermented black barley and quinoa with Lactobacillus (FG) against cognitive impairments triggered by an HFD and to investigate the microbiota-gut–brain axis mechanisms involved. C57BL/6J mice were randomized into four groups: the normal control group (NC, n = 10), the high-fat diet group (HFD, n = 10), the high-fat diet group supplemented with FG (HFG, 10 mL per kg BW, n = 10), and the high-fat diet group supplemented with Lactobacillus (HFL, 10 mL per kg BW, n = 10). Our results showed that the FG intervention enhanced the behavioral and locomotor skills of the mice, elevated the levels of dopamine (DA) and norepinephrine (NPI) in brain tissues, and alleviated synaptic ultrastructural damage in the hippocampus. Furthermore, FG intervention was observed to exert a protective effect on both the blood–brain barrier and the colonic barrier, as evidenced by an increase in the mRNA levels of Zona occludens-1 (ZO-1), Claudin-4, and Occludin in the hippocampus and colon. These beneficial effects may be attributed to FG's regulation of gut microbiota dysbiosis, which involves the restoration of intestinal flora diversity, reduction of the Firmicutes/Bacteroidetes (F/B) ratio, and a decrease in the levels of pro-inflammatory bacteria such as s_Escherichia coli E and g_Escherichia; moreover, there was an increase in the abundances of anti-inflammatory bacteria, such as s_Bacteroides thetaiotaomicron and s_Parabacteroides goldsteinii. Metagenomic analysis revealed that the FG treatment downregulated the lipopolysaccharide (LPS) pathway and upregulated neurotransmitter biosynthetic pathways. These probiotic effects of FG resulted in reduced production and “leakage” of LPS and decreased mRNA expression of Toll-like receptor 4 (Tlr4), cluster of differentiation 14 (CD14), and myeloid differentiation factor 88 (Myd88) in hippocampal and colon tissues. Consequently, a reduction was observed in the levels of inflammatory cytokines in the serum, hippocampus, and colon, along with suppression of the immunoreactivity of microglia and astrocytes. Our results suggest that FG may serve as an intervention strategy for preventing cognitive impairments caused by an HFD.
研究领域:
营养神经科学
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微生物组研究
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神经免疫学
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胃肠科学
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宏基因组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）