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
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
RSC Medicinal Chemistry
·
2024
·
IF 4.1
Die Zhang,Wenping Wang,Huiping Ou,Jinhua Ning,Yingxun Zhou,Jin Ke,Anguo Hou,Lingyun Chen,Peng Li,Yunshu Ma,Wenbin Jin
To develop new anti-inflammatory agents with improved pharmaceutical profiles, a series of novel chalcone analogues were designed and synthesized. In vitro anti-inflammatory activity of these compounds has been evaluated by screening inhibitory effects of the NO production in RAW264.7 cell lines. The most promising compounds 3h and 3l were selected to further investigated by assessment of their dose-dependent inhibitory activity against cytokines such as TNF-α, IL-1β, IL-6, and PGE2 release. The further study also indicated that 3h and 3l could significantly suppress expressions of iNOS and COX-2 through NF-κB/JNK signaling pathway. Furthermore, compounds 3h and 3l could also remarkably inhibit the mRNAs expressions of inflammation-related genes. Docking simulation was conducted to position compounds 3h and 3l into the iNOS binding site to predict the probable binding mode. In conclusion, a series of chalcone analogues with reasonable drug-likeness obtained by in silico rapid prediction could be used as promising lead candidates.
研究领域:
药理学
·
炎症研究
·
药物发现
✓ 已验证
DOI
PubMed
高影响因子
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
·
2024
·
IF 1.5
Chen Jiye,Chen Jiayao,Li Qinxia,Hu Minxia,Zhong Xingxing,Yu Liang,Zhang Xi,Huang Hongyu,Liu Jing,Huang Ziyi,Liu Xinyi,Xiong Wu
This study aimed to explore the potential of using mesenchymal stem cell (MSC)-derived exosomes (MSC-Exos) pre-treated with Astragaloside IV (ASIV) to alleviate inflammation in high glucose (HG)-damaged endothelial cells. MSC-Exos were isolated from untreated MSCs and ASIV-pre-treated MSCs, and their characteristics were assessed. The expression of miR-146a-5p in MSC-Exos was determined, and it was found that ASIV treatment enhanced its expression. In order to assess the impact of highly miR-146a-5p-expressing MSC-Exos on HG-injured endothelial cells, we established a model of HG-induced inflammation using human umbilical vein endothelial cells (HUVECs). The study measured cell viability, apoptosis, tube formation, and levels of inflammatory cytokines among the different treatment groups. It was found that transferring MSC-Exos with high miR-146a-5p expression to HG-damaged HUVECs increased cell viability and tube formation ability while reducing the number of apoptotic cells. Additionally, changes in inflammatory factors indicated a reduction in the inflammatory response. Further investigation demonstrated that miR-146a-5p inhibited the expression of TNF receptor associated factor 6 (TRAF6) and phosphorylated NF-κB, which are involved in the inflammatory response. This resulted in the alleviation of inflammation in HG-damaged endothelial cells. In summary, our findings indicate that ASIV treatment stimulated the secretion of MSC-Exos that exhibited increased levels of miR-146a-5p. These exosomes, in turn, regulated the TRAF6/NF-κB pathway. As a result of this modulation, the inflammatory response in HG-damaged endothelial cells was alleviated. These findings offer a fresh approach to addressing vascular complications associated with diabetes, which could lead to novel treatment strategies in the field.
研究领域:
药理学
·
细胞生物学
·
分子生物学
·
糖尿病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC MUSCULOSKELETAL DISORDERS
·
2024
·Vol. 25
·期 1
·1-10
·
IF 2.2
Lai Zhen,Li Mingming,Yang Xiaodong,Xian Zhenjie
Osteoporosis is caused by the imbalance of osteoblasts and osteoclasts. The regulatory mechanisms of differentially expressed genes (DEGs) in pathogenesis of osteoporosis are of significant and needed to be further investigated. GSE100609 dataset downloaded from Gene Expression Omnibus (GEO) database was used to identified DEGs in osteoporosis patients. KEGG analysis was conducted to demonstrate signaling pathways related to enriched genes. Osteoporosis patients and the human mesenchymal stem cells (hMSCs) were obtained for in vivo and in vitro resaerch. Lentivirus construction and viral infection was used to knockdown genes. mRNA expression and protein expression were detected via qRT-PCR and western blot assay separately. Alkaline phosphatase (ALP) activity detection, alizarin Red S (ARS) staining, and expression of bone morphogenetic protein 2 (BMP2), osteocalcin (OCN) and Osterix were evaluated to determine osteoblast differentiation capacity. UL-16 binding protein 1 (ULBP1) gene was upregulated in osteoporosis and downregulated in differentiated hMSCs. Knockdown of ULBP1 increased ALP activity, mineralization ability evaluated by ARS staining, expression of BMP2, OCN and Osterix in differentiated hMSCs. Furthermore, rescue experiment demonstrated that suppressed ULBP1 boosted osteoblast differentiation by activating TNF-β signaling pathway. Knockdown of ULBP1 gene could promoted osteoblast differentiation by activating TNF-β signaling pathway in differentiated hMSCs. ULBP1 may be a the Achilles’ heel of osteoporosis, and suppression of ULBP1 could be a promising treatment for osteoporosis.
研究领域:
分子生物学
·
干细胞研究
·
骨骼生物学
·
基因组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
·
2021
·
IF 2.351
Chijian Zhang,Yongjie Lu,Yong Ai,Xian Xu,Siyang Zhu,Bing Zhang,Minghui Tang,Lanyue Zhang,Tinggang He
Glabridin, a compound of the flavonoid, has shown outstanding skin-whitening and anti-aging properties, but its water insolubility limits its wide application. Therefore, glabridin liposome (GL) has been developed to improve its poor bioavailability, while there are few studies to evaluate its amelioration of UVB- induced photoaging. This study is performed to investigate the amelioration of GL against UVB- induced cutaneous photoaging. The prepared GL has a spheroidal morphology with an average diameter of 200 nm. The GL shows lower cytotoxicity than glabridin, but it has a more effective role in inhibition of melanin. Moreover, the application of GL can effectively relieve UV radiation induced erythema and leathery skin, associated with the down-regulated expression of inflammatory cytokines (TNF-α, IL-6 and IL-10). Taken together, these results demonstrate that GL has potentials as topical therapeutic agents against UVB radiation induced skin damage through inhibiting inflammation.
研究领域:
药学
·
皮肤病学
·
化妆品科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2020
·
IF 4.96
Junke Song,Li Zhang,Yanfeng Xu,Dezhi Yang,Li Zhang,Shiying Yang,Wen Zhang,Jinhua Wang,Shuo Tian,Shengqian Yang,Tianyi Yuan,Ailin Liu,Qi Lv,Fengdi Li,Hongqi Liu,Biyu Hou,Xiaozhong Peng,Yang Lu,Guanhua Du
Baicalein is the main active compound of Scutellaria baicalensis Georgi, a medicinal herb with multiple pharmacological activities, including the broad anti-virus effects. In this paper, the preclinical study of baicalein on the treatment of COVID-19 was performed. Results showed that baicalein inhibited cell damage induced by SARS-CoV-2 and improved the morphology of Vero E6 cells at a concentration of 0.1 μM and above. The effective concentration could be reached after oral administration of 200 mg/kg crystal form β of baicalein in rats. Furthermore, baicalein significantly inhibited the body weight loss, the replication of the virus, and relieved the lesions of lung tissue in hACE2 transgenic mice infected with SARS-CoV-2. In LPS-induced acute lung injury of mice, baicalein improved the respiratory function, inhibited inflammatory cell infiltration in the lung, and decreased the levels of IL-1β and TNF-α in serum. In conclusion, oral administration of crystal form β of baicalein could reach its effective concentration against SARS-CoV-2. Baicalein could inhibit SARS-CoV-2-induced injury both in vitro and in vivo. Therefore, baicalein might be a promising therapeutic drug for the treatment of COVID-19.
研究领域:
药理学
·
病毒学
·
免疫学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED MICROBIOLOGY
·
2019
·Vol. 127
·期 6
·1716-1726
·
IF 2.683
Cheng R.,Wang L.,Li J.,Fu R.,Wang S.,Zhang J.
AimsTo purify and characterize an exopolysaccharide (EPS) from an Agrobacterium strain ZCC3656 with high EPS‐secreting performance and investigate its anti‐inflammatory activity using lipopolysaccharide (LPS)‐induced macrophage cells in an acute liver injury mouse model.Methods and ResultsTwelve rhizobial strains were compared for EPS fermentation production in modified M9 salts supplemented with mannitol or sucrose as the sole carbon source. Agrobacterium sp. ZCC3656 exhibited the highest EPS yield (21·1 g l−1) and was characterized for EPS production by carbon source utilization, time course fermentation and serial subcultivation assays. The EPS, designated Riclin, was purified by deproteinization using the Sevag method. The combined results of gel permeation chromatography, monosaccharide composition, methylation analysis and nuclear magnetic resonance analyses indicated that Riclin is a succinoglycan‐like polysaccharide comprised of glucose, galactose, succinate and pyruvate at a ratio of 7·8. : 1·0 : 0·9 : 1·1 and has an molecular weight of approximately 2·5 × 106 Da. Riclin inhibited TNF‐α, IL‐1β and IL‐6 expression in LPS‐stimulated RAW 264.7 macrophage cells in a dose‐dependent manner. In addition, Riclin pretreatment increased the survival rate of D‐Gal/LPS treated mice, inhibited serum ALT and AST activities and reduced the production of the inflammatory mediators TNF‐α, IL‐1β and IL‐6.ConclusionsAgrobacterium sp. ZCC3656 is a highly stable EPS‐producing strain. The EPS Riclin from ZCC3656 is a succinoglycan‐type polysaccharide that is noncytotoxic and exhibits remarkable anti‐inflammatory effects in vivo and in vitro.Significance and Impact of the StudySuccinoglycans are well known for good rheological properties and their physiological interactions with plants. However, their potential activity towards mammals has received little attention. Our study revealed that the succinoglycan Riclin exhibited excellent anti‐inflammatory activities and could be considered as a promising reagent in anti‐inflammatory treatment.
研究领域:
微生物学
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Natural Products and Bioprospecting
·
2024
·Vol. 14
·期 1
·1-12
·
IF 4.8
Shi Yuru,Zhang Xiaoqian,Pei Shengji,Wang Yuhua
Adenosma buchneroides Bonati, also known as fleagrass, is an important medicinal plant used by the Akha (Hani) people of China for treating inflammation-related skin swelling, acne, and diarrhoea, among other conditions. In this study, we aimed to evaluate the anti-inflammatory activities and explore the molecular mechanisms of fleagrass on treating skin swelling and acne. The results demonstrated that fleagrass inhibited the enzymatic activities of 5-LOX and COX-2 in vitro, and decreased the release of NO, IL-6, TNF-α, and IL-10 in the LPS-induced RAW264.7 macrophages. The levels of proteins associated with the nuclear factor-kappa B (NF-κB) pathway were examined by western blotting and immunofluorescence, demonstrating that fleagrass downregulated the expression of TLR4, MyD88, NF-κB/p65, and iNOS and blocked the nuclear translocation of NF-κB/p65. Furthermore, fleagrass exhibited acute anti-inflammatory activity in paw oedema models. The results confirm that fleagrass exhibits remarkable anti-inflammatory activity and can be used in alleviating inflammation, suggesting that fleagrass has the potential to be a novel anti-inflammatory agent. Graphical Abstract
研究领域:
民族药理学
·
药理学
·
炎症
·
药用植物
✓ 已验证
产品关联
DOI
PubMed
高影响因子
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
·
2019
·
IF 2.086
Rui-Li Zhu,Ying-Kun Zhi,Lang Yi,Jin-Fang Luo,Jing Li,Sha-Sha Bai,Liang Liu,Pei-Xun Wang,Hua Zhou,Yan Dong
Objective: To investigate the cellular mechanism that sinomenine (SIN) inhibits inflammation in macrophages induced by LPS through α7 nicotinic acetylcholine receptor (α7nAChR).Materials and methods: RAW264.7 cells were stimulated with LPS and treated by SIN or nicotine (Nic). A selective antagonist of α7nAChR, α-bungarotoxin (BTX) was used to block α7nAChR. AG490 was used to inhibit JAK2 activation. ELISA was performed to detect the levels of TNF-α and MCP-1. Western blotting was used to analyze the expression of MIF, MMP-9, CD14, TLR4, STAT3 and p-STAT3. Intracellular-free calcium level was measured by Fluorescent probe fluo-3/AMResults: SIN inhibited the production of TNF-α, MCP-1, MIF, and MMP-9, decreased the expression of CD14 and TLR4, and inhibited the release of intracellular-free calcium from intracellular stores in RAW 264.7 cells stimulated by LPS. JAK-specific inhibitor AG490 attenuated the inhibitory effect of SIN on TNF-α. SIN increased the phosphorylation of STAT3. And the above effects of SIN were attenuated by antagonist of α7nAChR.Conclusions: SIN can decrease the expression of CD14/TLR4 and intracellular free calcium level, activate JAK2/STAT3 pathway to inhibit inflammatory response through α7nAChR in macrophages.
研究领域:
免疫学
·
药理学
·
细胞生物学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Cancer
·
2019
·
IF 3.182
Wanru Ma,Juan Ma,Ting Lei,Man Zhao,Man Zhang
To investigate whether CD155 is an attractive target for T cell-mediated immunotherapy against human bladder cancer, we examined the novel bispecific antibody anti-CD3 x anti-CD155 (CD155Bi-Ab) for its ability to redirect activated T cells (ATCs) to target bladder cancer cells was examined. Expression of CD155 was detected by flow cytometry on the surface of bladder cancer cells, including T24 and Pumc-91 cells, and their chemotherapeutic drug-resistant counterparts. ATCs generated from healthy donors were stimulated with anti-CD3 monoclonal antibody, anti-CD28 monoclonal antibody and interleukin-2 (IL-2) for 14 days. The cytotoxic activity of ATCs armed with CD155Bi-Ab against bladder cancer cells was detected by LDH and luciferase quantitative assay. Furthermore, ATCs generated from bladder cancer patients were also armed with CD155Bi-Ab to verity the cell killing by the same methods. In contrast to unarmed ATCs, CD155Bi-armed ATCs against bladder cancer cells were increased cytotoxic activity at effector/target (E/T) ratios of 5:1, 10:1, and 20:1, with more IFN-γ, TNF-α secreting. It is worth noting that in spite of the presence of immunosuppression in bladder cancer patients and the drug resistance in chemotherapeutic drug-resistant cancer cell lines, not only the anti-tumor effect of CD155Bi-armed ATCs generated from bladder cancer patients still showed significantly but only higher level of activation marker CD69 was expressed. Taken together, our results suggest that CD155 is an effective target for the CD155-positive bladder cancer. And CD155Bi-Ab-armed ATCs are promisingly to provide a novel strategy for current CD155-positive bladder cancer therapy.
研究领域:
肿瘤学
·
免疫疗法
·
分子生物学
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Xuejun Yuan,Wenjie Chen,Rui Li,Huijun Guo,Chunyang Wang
Deoxynivalenol (DON) is one of the most prevalent mycotoxins and can induce weight loss and vomiting in animals. This study aimed to elucidate the molecular mechanisms underlying DON-induced anorexia in rabbits through the microbial-gut-brain axis. A total of forty rabbits were randomly divided into a DON group and a control group, receiving 1.5 mg/kg.BW of DON and an equivalent volume of saline daily via intragastric administration, respectively. The pre-treatment period lasted for 7 days, followed by a formal experimental period of 24 days. The findings revealed that DON exposure significantly reduced daily food intake and weight gain, leading to intestinal apoptosis and barrier injuries. 16S rRNA sequencing data indicated that DON exposure decreased the diversity and richness of cecal microflora, suppressed probiotic populations, and disrupted host lipid metabolism. RNA-Seq and iTRAQ data were used to cross-analyze the shared differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) in the hypothalamus and jejunum, along with their shared enrichment pathways, indicating that TNF-α, NF-κB, and NPY may play pivotal roles in DON-induced anorexia. qRT-PCR and Western blotting results confirmed significant increases in mRNA and protein expression levels of TNF-α, NF-κB and 5-HT2A in both the hypothalamus and jejunum. In conclusion, DON ingestion in rabbits can disrupt the intestinal barrier, up-regulate the expression of IFN-γ, TNF-α, NF-κB, and 5-HT2A in the intestine, and trigger an immuno-inflammatory response in the hypothalamus via the microbial-gut-brain axis, ultimately resulting in appetite suppression and weight loss.
研究领域:
毒理学
·
分子生物学
·
微生物学
·
动物科学
·
营养学
✓ 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）