Frontiers in Immunology
·
2022
·
IF 8.786
Gu Lingui,Sun Mingjiang,Li Ruihao,Zhang Xingyu,Tao Yihao,Yuan Ye,Luo Xu,Xie Zongyi
Neuroinflammation has been proven to exert an important effect on brain injury after intracerebral hemorrhage (ICH). Previous studies reported that Didymin possessed anti-inflammatory properties after acute hepatic injury, hyperglycemia-induced endothelial dysfunction, and death. However, the role of Didymin in microglial pyroptosis and neuroinflammation after ICH is unclear. The current study aimed to investigate the effect of Didymin on neuroinflammation mediated by microglial pyroptosis in mouse models of ICH and shed some light on the underlying mechanisms. In this study, we observed that Didymin treatment remarkably improved neurobehavioral performance and decreased BBB disruption and brain water content. Microglial activation and neutrophil infiltration in the peri-hematoma tissue after ICH were strikingly mitigated by Didymin as well. At the molecular level, administration of Didymin significantly unregulated the expression of Rkip and downregulated the expression of pyroptotic molecules and inflammatory cytokines such as Nlrp3 inflammasome, GSDMD, caspase-1, and mature IL-1β, TNF-α, and MPO after ICH. Besides, Didymin treatment decreased the number of Caspase-1-positive microglia and GSDMD-positive microglia after ICH. Inversely, Locostatin, an Rkip-specific inhibitor, significantly abolished the anti-pyroptosis and anti-neuroinflammation effects of Didymin. Moreover, Rkip binding with Asc could interrupt the activation and assembly of the inflammasome. Mechanistically, inhibition of Caspase-1 by VX-765 attenuated brain injury and suppressed microglial pyroptosis and neuroinflammation by downregulation of GSDMD, mature IL-1β, TNF-α, and MPO based on Locostatin-treated ICH. Taken together, Didymin alleviated microglial pyroptosis and neuroinflammation, at least in part through the Asc/Caspase-1/GSDMD pathway via upregulating Rkip expression after ICH. Therefore, Didymin may be a potential agent to attenuate neuroinflammation via its anti-pyroptosis effect after ICH.
研究领域:
神经科学
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药理学
·
炎症
·
神经病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Ting Wang,Xingliang Xiong,Na Xiao,Yizhong Yan,Xiaoyang Liu,Qi Xie,Xian Su,Maosheng Chen,Jing Peng,Siqi Wang,Hua Mei,Ge Lin,Fei Gong,Lamei Cheng
Immune dysregulation has been summarized as a critical factor in the occurrence and development of Polycystic ovary syndrome (PCOS), but potential mediators and mechanisms remain unclear. Our previous study showed that CD19 + B cells were involved in the pathogenesis of dehydroepiandrosterone (DHEA)-induced PCOS mice. Here, we studied the therapeutic potential of anti-CD19 antibody (aCD19 Ab) on DHEA-induced PCOS mice. The results showed that aCD19 Ab treatment improved ovarian pathological structure and function of PCOS mice, manifested by an increased number of corpus luteum, a decreased number of cystic follicles and atretic follicles, and regular estrus cycles. The aCD19 Ab treatment reduced the proportion of splenic CD21 + CD23 low marginal zone B cells as well as the level of serum IgM and decreased the percentage of peripheral blood and splenic neutrophils. In particular, aCD19 Ab treatment reduced the apoptosis of granulosa cells and macrophage infiltration in ovarian secondary follicles of PCOS mice, as well as the expression of TNF-α in ovarian tissue and serum TNF-α levels. Moreover, we confirmed that TNF-α induced the apoptosis of human ovarian granulosa tumor cell line cells in vitro. Thus, our work demonstrates that aCD19 Ab treatment improves ovarian pathological phenotype and function by reducing local and systemic inflammation in PCOS mice, which may provide a novel insight into PCOS therapy.
研究领域:
生殖生物学
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免疫学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Dalin Sun,Dong Xing,Dandan Wang,Yuanyuan Liu,Bin Cai,Weimin Deng,Qinglin Hu,Wenjun Ma,Baofang Jin
Background: Chronic non-bacterial prostatitis (CNP), one of the most common chronic diseases in urology, leads to pain in the prostate and dysuria, critically affecting the physical or mental health of patients. However, there are no standard treatment approaches for the treatment of CNP in the clinic. Although the clinical application of Bushen Daozhuo granule (BSDZG) offers hope to CNP patients in China, the mechanisms of BSDZG in treating CNP are still not entirely clear. Hence, we aimed to investigate the novel therapeutic mechanisms of BSDZG on CNP. Methods: In this study, we first assayed the prostate index of rats and then determined the anti-inflammatory and anti-apoptotic effects of BSDZG on CNP in vivo and in vitro by employing ELISA kits and TUNEL staining. Next, we investigated whether the anti-inflammatory and anti-apoptotic mechanisms of BSDZG on prostate protein-induced rats and lipopolysaccharide (LPS) induced RWPE-1 cells were related to the AKT, p38 MAPK, and NF-κB pathways with the help of Western blot. Finally, the influence of BSDZG on the interaction between the p38 MAPK and NF-κB pathway in LPS-induced RWPE-1 cells was explored by adopting dehydrocorydaline (DHC, p38 MAPK activator) with the help of ELISA kits and Western blot. Results: In vivo , BSDZG effectively reduced the prostate index. In vivo and in vitro , BSDZG dramatically declined the level of two pro-inflammatory cytokines, TNF-α and IL-1β, as well as the apoptosis rate. Moreover, in vivo and in vitro , BSDZG memorably upregulated the expression level of p-AKT, and substantially downregulated the expression level of p-p38 MAPK and NF-κB2. The activation of p38 MAPK significantly reversed the moderation effects of BSDZG on the level of TNF-α and IL-1β, as well as the expression level of p-p38 MAPK and NF-κB2 in vitro . Conclusion: To sum up, the in vivo and in vitro therapeutic mechanisms of BSDZG on CNP were reflected as the anti-inflammation and anti-apoptosis that was formed by inhibiting the level of pro-inflammatory cytokines, TNF-α and IL-1β, to regulate the AKT, p38 MAPK, and NF-κB pathways, and the anti-inflammatory effect of BSDZG was realized by suppressing the p38 MAPK pathway to inhibit the downstream NF-κB pathway.
研究领域:
泌尿外科
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药理学
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分子生物学
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2024
·
IF 2.5
Songqin Yang,Mao Zhao,Yuhan Feng,Xia Zhang,Qiuhong Li,Wenwen Jiang,Daoping Wang
Toddalia asiatica (L.) Lam. (TA) is a traditional folk medicine of ethnic minorities in the southwest of China. It is widely used in the treatment of dispersing blood stasis and activating blood. However, the effective substance and pharmacological mechanism have not been fully elucidated. The zebrafish larvae were treated with Phenylhydrazine (PHZ) to establish a thrombus model, and the staining intensity of zebrafish red blood cells was analyzed. The antithrombotic activity of TA was verified for the first time, and it was found that the inhibition rate of TA on thrombosis was up to 60.85 %. The chemical ingredients of TA were collected by combining UPLC-HRMS analysis and the literature research. Network pharmacology revealed that six key targets were obtained, which including TNF, AKT1, EGFR, PTGS2, PPARG, and IFNG. It showed that the PI3K-Akt pathway was a core signaling pathway. Coagulation factor III(TF), playing an important role in the process of hemostasis and thrombosis, which ranks high in the PPI network. Moreover, the results of molecular docking showed that the active components had a strong binding force with TF, which indicated that TF might be the key target of TA in treating thrombosis. In vitro experiments showed that TA could inhibit TNF-α-induced high expression of TF in EA.hy926 cells. In addition, TA could inhibit TNF-α-activated expression of Akt, IκBα and P65 protein phosphorylation in PI3K-Akt pathway. The results showed that TA had antithrombotic activity and exerted an antithrombotic effect by inhibiting the expression of TF through the PI3K-Akt-NF-κB signaling pathway.
研究领域:
药理学
·
分子生物学
·
传统中药
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斑马鱼研究
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网络药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2020
·
IF 3.383
Guangduo Zhu,Xiaowei Yang,Cheng Peng,Lei Yu,Yingjie Hao
The transplantation of bone marrow mesenchymal stem cells (BMSCs) has been found to be used as an effective therapy of intervertebral disc degeneration (IDD). However, the underlying mechanisms of BMSCs in the progress of IDD are not fully explained. In this study, we found that exosomes derived from BMSCs (BMSCs-Exos) inhibited the apoptotic rate , extracellular matrix (ECM) degradation, and fibrosis deposition in TNF-α-induced nucleus pulposus cells (NPCs). Importantly, the level of miR-532–5p was observed to be decreased in apoptotic NPCs, but abundant in BMSCs-Exos with TNF-α treatment. The results showed that BMSCs-Exos under TNF-α stimuli exerted better effects on NPCs than BMSCs-Exos, which might be mitigated by the inhibition of miR-532–5p in BMSCs-Exos. The gain-of-function results suggested that the direct overexpression of miR-532–5p in NPCs could inhibit TNF-α-induced increase of apoptotic process, activation of apoptotic proteins, imbalance of anabolism/catabolism levels, and accumulation of collagen I. In addition, RASSF5 was demonstrated to be a target of miR-532–5p. Knockdown of RASSF5 could decrease the apoptotic cells and reduce the activated apoptotic protein levels in TNF-α-induced NPCs. Overall, these data indicate that exosomes from BMSCs may suppress TNF-α-induced apoptosis, ECM degradation, and fibrosis deposition in NPCs through the delivery of miR-532–5p via targeting RASSF5. This work provides a promising therapeutic strategy for the progress of IDD.
研究领域:
干细胞生物学
·
再生医学
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分子生物学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2015
·
IF 4.074
Qing Zhang,Yi Xu,Sheng Zou,Xiaodan Zhang,Kun Cao,Qi Fan
The alkali-extractable polysaccharides (APMPs) were isolated from the water extracted residues of Radix Polygoni Multiflori, and further purified by DEAE-52 cellulose and Sephadex G-100 column chromatography to obtain a homogeneous polysaccharide (APMP-2) with molecular weights of 7724.8 Da. HPLC chromatography analysis identified that APMP-2 was a heteropolysaccharides and mainly composed of Galactose and Xylose with a molar ratio of 4.31: 1.06. It was shown that both APMP and APMP-2 were of activation effects on splenocytes and peritoneal macrophages, and also significantly restore the proliferation rate, phagocytic index and cytokine (IL-2 and TNF-α) production level of 5-FU-treated splenocytes/peritoneal macrophages in a dosage-dependent manner. The results suggested that polysaccharides presented in Radix Polygoni Multiflori water-extracted residues possessed immunomodulatory activity and could be used as potential immunomodulators, and this finding could be a reference for the utilization of Radix Polygoni Multiflori water extracted residues.
研究领域:
药理学
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免疫学
·
植物化学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2018
·
IF 3.04
Yulong Kong,Xiaoguang Gao,Changyuan Wang,Chenqing Ning,Kexin Liu,Zhihao Liu,Huijun Sun,Xiaodong Ma,Pengyuan Sun,Qiang Meng
Accumulation of toxic bile acids in liver could cause cholestasis and liver injury. The purpose of the current study is to evaluate the hepatoprotective effect of yangonin , a product isolated from an edible botanical Kava against lithocholic acid (LCA)-induced cholestasis, and further to elucidate the involvement of farnesoid X receptor (FXR) in the anticholestatic effect using in vivo and in vitro experiments. The cholestatic liver injury model was established by intraperitoneal injections of LCA in C57BL/6 mice. Serum biomarkers and H&E staining were used to identify the amelioration of cholestasis after yangonin treatment. Mice hepatocytes culture, gene silencing experiment, real-time PCR and Western blot assay were used to elucidate the mechanisms underlying yangonin hepatoprotection . The results indicated that yangonin promoted bile acid efflux and reduced hepatic uptake via an induction in FXR-target genes Bsep , Mrp2 expression and an inhibition in Ntcp , all of which are responsible for bile acid transport. Furthermore, yangonin reduced bile acid synthesis through repressing FXR-target genes Cyp7a1 and Cyp8b1, and increased bile acid metabolism through an induction in gene expression of Sult2a1, which are involved in bile acid synthesis and metabolism. In addition, yangonin suppressed liver inflammation through repressing inflammation-related gene NF-κB, TNF-α and IL-1β. In vitro evidences showed that the changes in transporters and enzymes induced by yangonin were abrogated when FXR was silenced. In conclusions, yangonin produces protective effect against LCA-induced hepatotoxity and cholestasis due to FXR-mediated regulation. Yangonin may be an effective approach for the prevention against cholestatic liver diseases.
研究领域:
药理学
·
肝病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Yu Bai,Mi Tian,Ping He,Yongzhe Zhang,Jie Chen,Zixia Zhao,Jingsi Lan,Beiru Zhang
Prolonged renal inflammation contributes to fibrosis, which may eventually lead to irreversible chronic kidney disease. Our previous work demonstrated that LIM and cysteine-rich domain 1 (LMCD1) are associated with renal interstitial fibrosis in a 21-day unilateral ureteral obstruction (21UUO) mouse model. Interestingly, based on the gene expression omnibus database, we found that LMCD1 is enhanced in the mouse kidney as early as 5, 7, and 10 days following unilateral ureteral obstruction (UUO), suggesting that LMCD1 may exert its function in an earlier phase. To validate this conjecture, a 7UUO mouse model and a tumor necrosis factor-α (TNF-α)-stimulated HK-2 cell model were established, followed by injection of adenovirus vectors carrying short hairpin RNA targeting LMCD1. LMCD1 silencing ameliorated renal collagen deposition and reduced the expression of profibrotic factors in the 7UUO model. LMCD1 silencing alleviated tubulointerstitial inflammation by mitigating F4/80 + cell infiltration, monocyte chemoattractant protein-1 release and nuclear factor-κB activation. In addition, LMCD1 silencing suppressed NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and nuclear factor of activated T cells 1 (NFATc1) nuclear translocation. Consistent results were obtained in TNF-α-stimulated HK-2 cells in vitro . Mechanistically, the transcriptional coactivator LMCD1 cooperates with the transcription factor NFATc1 to increase NLRP3 expression. Collectively, these findings suggest that LMCD1 participates in tubulointerstitial inflammation via an LMCD1-NFATc1/NLRP3 mechanism. LMCD1 may therefore become a potential target for the control of renal inflammation and fibrosis.
研究领域:
肾病学
·
炎症
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-16
·
IF 9.429
Liu Qiqi,Zhang Ying,Huang Jingkai,Xu Zhourui,Li Xiang,Yang Jingyu,Huang Haoqiang,Tang Shiqi,Chai Yujuan,Lin Jinbo,Yang Chengbin,Liu Jia,Lin Suxia
The colonization of bacterial pathogens is a major concern in wound infection and becoming a public health issue. Herein, a core–shell structured Ag@MSN (silver core embedded with mesoporous silica, AM)-based nanoplatform was elaborately fabricated to co-load ciprofloxacin (CFL) and tumor necrosis factor-α (TNF-α) small interfering RNA (siTNF-α) (AMPC@siTNF-α) for treating the bacterial-infected wound. The growth of bacterial pathogens was mostly inhibited by released silver ions (Ag + ) and CFL from AMPC@siTNF-α. Meanwhile, the loaded siTNF-α was internalized by macrophage cells, which silenced the expression of TNF-α (a pro-inflammatory cytokine) in macrophage cells and accelerated the wound healing process by reducing inflammation response. In the in vivo wound model, the Escherichia coli (E. coli) -infected wound in mice almost completely disappeared after treatment with AMPC@siTNF-α, and no suppuration symptom was observed during the course of the treatment. Importantly, this nanoplatform had negligible side effects both in vitro and in vivo. Taken together, this study strongly demonstrates the promising potential of AMPC@siTNF-α as a synergistic therapeutic agent for clinical wound infections. Graphical Abstract
研究领域:
纳米技术
·
药学
·
生物医学工程
·
传染病
·
伤口愈合
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2022
·Vol. 32
·期 44
·2206261
·
IF 19.924
Chao Li,Yawei Du,Hongzhi Lv,Jun Zhang,Pengzhen Zhuang,Wu Yang,Yingze Zhang,Juan Wang,Wenguo Cui,Wei Chen
Artemisinin and its derivatives (artemisinins) are first-line chemotherapeutic agents of lethal malaria, which also showed tremendous value in many other diseases including chronic inflammation. Unfortunately, almost all artemisinins are rapid-acting medicines with an extremely short half-life in vivo, which significantly limits their clinical application for these new adaptation diseases. In this study, a locally injectable long-acting gene/artemisinin co-delivery nano-microplex consisting of a biodegradable hyaluronic acid (HA) microsphere and releasable gene/artemisinin co-delivery nano-lipoplex is developed first, to obtain an improved efficacy for rheumatoid arthritis (RA). Briefly, a cationic multicomponent drug-embedded liposome with pharmacological activity is first reported based on two novel artemisinin derivatives (dAPC and dACC), which possess mimic phospholipids and cationic lipids, respectively. A cationic artemisinin-embedded lipoplex is first reported as a medicative gene carrier here. An in situ injectable TNF-α siRNA/artemisinin co-delivery nano-microplex (MTAsi@MG) is further prepared by immobilization of TNF-α siRNA/lipoplex on porous microfluidic HA microspheres. Using this nano-microplex for intra-articular injection, the sustaining activity of gene therapy and artemisinin efficacy for RA long-term treatment is first realized. Undoubtedly, this intra-articular injectable TNF-α siRNA/artemisinin co-delivery nano-microplex based on dAPC/dACC lipoplex and microfluidic microspheres would be one of the most potent gene/drug co-delivery systems for RA therapy.
研究领域:
药学
·
生物技术
·
纳米医学
·
风湿病学
·
分子生物学
✓ 已验证
DOI
高影响因子
Plants-Basel
·
2026
·Vol. 15
·期 17
·2654
·
IF 4.7
Feiran Hu,Wenzhao Zhou,Nong Zhou,Lanlan Wan,Linyun Pu,Caiyun Fu,Hua Zhang,Junsheng Qi
Lycopus lucidusTurcz. var.hirtusRegel (L. lucidusvar.hirtus) is a medicinal herb traditionally used in Chinese folk medicine for the treatment of inflammatory disorders, joint pain, and rheumatoid arthritis (RA)-like symptoms. However, systematic research on the bioactive flavonoids of this herb in RA-related cellular models is limited. The aim of this study was to isolate the main flavonoid from this herb and evaluate its in vitro anti-inhibitory effects in TNF-α-induced human RA fibroblast-like synoviocytes (HFLS-RA). Flavonoids were extracted, purified, and isolated using chromatographic techniques. The structure was elucidated by spectroscopic analysis. The effects of the isolated compound were assessed in a TNF-α-induced HFLS-RA cell model by evaluating pro-inflammatory cytokine secretion and cell proliferation/metabolic activity. A main flavonoid was identified as formononetin. Formononetin exhibited antioxidant activity and inhibited TNF-α-provoked inflammatory responses in HFLS-RA cells under cell-safe concentrations, as evidenced by reduced secretion of IL-6, IL-8, and IL-1β and suppression of TNF-α-induced hyperproliferation. In conclusion, formononetin is a major flavonoid constituent ofL. lucidusvar.hirtus, and these findings provide preliminary in vitro cellular evidence that formononetin exerts in vitro anti-inflammatory inhibitory activity on TNF-α-activated human RA fibroblast-like synoviocytes. Further in vivo and mechanistic studies are required to explore its potential for anti-RA-related pharmacological application.
✓ 已验证
DOI
PubMed
高影响因子
Scientific Reports
·
2023
·Vol. 13
·期 1
·1-11
·
IF 4.6
Lan Xiang,Qi Dongdong,Ren Hao,Liu Tao,Shao Hong,Zhang Jiantao
Damage to lamellar keratinocytes, an essential cellular component of the epidermal layer of hoof tissue, can have a detrimental effect on hoof health and the overall production value of dairy cows. We isolated and cultured cow lamellar keratinocytes using the Dispase II and collagenase methods. We purified them by differential digestion and differential velocity adherent methods at each passaging and identified them by keratin 14 immunofluorescence. We established an in vitro model of inflammation in laminar keratinocytes using LPS and investigated whether chicoric acid protects against inflammatory responses by inhibiting the activation of the TLR4/MAPK/NF-κB signaling pathway. The results showed that cow lamellar keratinocytes were successfully isolated and cultured by Dispase II combined with the collagenase method. In the in vitro inflammation model established by LPS, the Chicoric acid decreased the concentration of inflammatory mediators (TNF-α, IL-1β, and IL-6), down-regulated the mRNA expression of TLR4 and MyD88 (P < 0.01), down-regulated the expression of TLR4, MyD88, p-ERK, p-p38, IKKβ, p-p65, p-p50 (P < 0.05), and increased the IκBα protein expression (P < 0.05). In conclusion, Chicoric acid successfully protected cow lamellar keratinocytes from LPS-induced inflammatory responses by modulating the TLR4/MAPK/NF-κB signaling pathway and downregulating inflammatory mediators.
研究领域:
兽医学
·
免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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