JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Qibin Li,Yameng Wang,Qing Guo,Jie Cao,Yangjun Feng,Xue Ke
Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant potential in therapeutic applications for treating alopecia areata; however, the systemic adverse effects of oral administration and low absorption rate at the target site limit its application. Hence, to address this issue, we designed topical formulations of tofacitinib-loaded cationic lipid nanoparticles (TFB-cNLPs) with particle sizes of approximately 200 nm. TFB-cNLPs promoted percutaneous absorption and hair follicle targeting in an ex vivo pig ear model. TFB-cNLP decreased IFN-γ-induced alopecia areata symptoms in an in vitro follicle model by blocking the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. It also reduced the number of CD8 + NKG2D + T cells in a C3H mouse model of alopecia areata in vivo, thereby inhibiting the progression of alopecia areata and reversing hair loss. These findings suggest that TFB-cNLP enhanced hair follicle targeting and has the potential for topical treatment or prevention of alopecia areata.
研究领域:
药剂学
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皮肤科
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纳米技术
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免疫学
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产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2023
·
IF 4.1
Siwen Feng,Gonghao Xu,Yuchen Fu,Qi Ding,Yuanyuan Shi
Asthma is a chronic respiratory disease. Bergamot essential oil (BEO) is extracted from the bergamot peel, which is widely used as a medicinal and food plant in China. Modern pharmacological studies have confirmed that BEO has anti-inflammatory properties, suggesting potential in treating asthma. First, the main active ingredients of BEO were detected and analyzed by gas chromatography–mass spectrometry (GC-MS). Network pharmacology methods were used to explore the possible core targets and main pathways of BEO in asthma treatment. Then ovalbumin (OVA)-induced in vivo and lipopolysaccharide (LPS)-induced in vitro models were established to investigate the antiasthmatic effects of BEO. BEO showed a good antiasthmatic effect by improving lung inflammation and inhibiting collagen deposition. Then, enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR) were used to explore the possible mechanism of BEO in asthma treatment. Furthermore, experimental verification showed that BEO could suppress the release of inflammatory factors in vitro and inhibit the activation of MAPK and JAK-STAT signaling pathways. This study demonstrated the anti-inflammatory effects of BEO against asthma. Moreover, it supplies a theoretical basis for the clinical application of BEO.
研究领域:
药理学
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呼吸医学
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免疫学
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生物化学
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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 Science
·
2024
·
IF 14.3
Junjie Mao,Zhenqian Sun,Shidong Wang,Jianqiang Bi,Lu Xue,Lu Wang,Hongliang Wang,Guangjun Jiao,Yunzhen Chen
In this study, a novel bionic periosteum (BP)-bioactive glass fiber membrane (BGFM) is designed. The introduction of magnesium ion (Mg 2+ ) and zinc ion (Zn 2+ ) change the phase separation during the electrospinning (ES) jet stretching process. The fiber's pore structure transitions from connected to closed pores, resulting in a decrease in the rapid release of metal ions while also improving degradation via reducing filling quality. Additionally, the introduction of magnesium (Mg) and zinc (Zn) lead to the formation of negative charged tetrahedral units (MgO 4 2− and ZnO 4 2− ) in the glass network. These units effectively trap positive charged metal ions, further inhibiting ion release. In vitro experiments reveal that the deigned bionic periosteum regulates the polarization of macrophages toward M2 type, thereby establishing a conducive immune environment for osteogenic differentiation. Bioinformatics analysis indicate that BP enhanced bone repair via the JAK-STAT signaling pathway. The slow release of metal ions from the bionic periosteum can directly enhance osteogenic differentiation and vascularization, thereby accelerating bone regeneration. Finally, the bionic periosteum exhibits remarkable capabilities in angiogenesis and osteogenesis, demonstrating its potential for bone repair in a rat calvarial defect model.
研究领域:
生物材料
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组织工程
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骨再生
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免疫学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
VETERINARNI MEDICINA
·
2023
·
IF 0.7
Weifeng Zhang,Hualong Deng,Yanfen Liu,Shaohong Chen,You Liu,Yuntao Zhao
Peste des petits ruminants virus (PPRV), a member of the family Paramyxoviridae, belongs to the genus Morbillivirus. It causes devastating viral diseases in small ruminants and has been rapidly spreading over various regions in Africa, the Middle East, and Asia. Although vaccination is thought to be an effective management strategy against PPR infections, the heat sensitivity of PPRV vaccines severely restricts their use in regions with hot climates. In this research, we studied the antiviral activities of ribavirin and aimed to understand the potential mechanisms of action of ribavirin in the African green monkey kidney cells (Vero cells). In brief, the adsorption, intrusion, replication, and release of PPRV, as well as the mRNA expression level of RNA-dependent RNA polymerase ( RdRp ), were significantly inhibited in the ribavirin-treated Vero cells compared to those in the PPRV-infected cells that were not treated with ribavirin. Additionally, ribavirin has potential as an antiviral drug against PPRV, and its antiviral activity is mediated by the Janus kinase signal transducer and activator of transcription (JAK/STAT) and PI3K/AKT pathways.
研究领域:
兽医学
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病毒学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2021
·
IF 4.451
Xiaoyan Su,Ming Zhao,Xinyu Fu,Xiaodan Ma,Wei Xu,Songhua Hu
Polysaccharides from Rubus chingii Hu fruits (RFPs) were extracted, purified, characterized and investigated for immunomodulatory activity. Results indicated that RFPs were heteropolysaccharides with molecular weight of 51.7 kDa and contained carbohydrate contents of 96.83%. RFPs with characteristic absorptive peaks of polysaccharide structure and α-configuration were composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose and fucose with a molecular ratio of 0.08:0.17:0.16:0.48:5.73:1.00:1.79:0.03. RFPs promoted splenocyte proliferation, NO release, cytokine production and intracellular Ca 2+ concentration. The mechanism underlying splenocyte activation by RFPs was elucidated by RNA-Seq, in which 2214 differentially expressed genes (DEGs), 2030 GO terms and 92 KEGG pathways were identified. RFPs were further proved to induce a balanced Th1/Th2/Th17 response pattern through MAPK, NF-κB, Jak-STAT and Calcium signaling pathways in splenocytes. These findings provided a fundamental basis for the further application of RFPs as immunomodulators in food and medicine.
研究领域:
免疫学
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药理学
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分子生物学
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生物化学
✓ 已验证
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2022
·Vol. 32
·期 16
·2109173
·
IF 19.924
Jie Deng,Deqing Lin,Xiangyu Ding,Yuan Wang,YuHan Hu,Hui Shi,Lin Chen,Bingyang Chu,Lei Lei,Chunmei Wen,Jiaqing Wang,Zhiyong Qian,Xingyi Li
Peptide-drug conjugates (PDCs) are an important class of therapeutic agents that combine one or more active molecules with a short peptide via a biodegradable spacer to generate prodrugs. Here an antioxidant (i.e., 3,5-dihydroxybenzoic acid), a non-steroidal anti-inflammatory drug (i.e., ibuprofen, IPF), and a self-assembled peptide motif (i.e., Gly-Phe-Phe-Tyr-Asp, GFFYD) are integrated to produce a peptide-drug amphiphile, which self-assembles to form hydrogel and further exerts the synergistic effects, and consequently emerges high therapeutic efficacy. In the in vitro study toward lipopolysaccharide-activated RAW264.7 macrophages, the resulting hydrogel significantly reduces the production of cytokines (e.g., IL-1β, IL-6 and tumor necrosis factor-α (i.e., TNF-α)) compared with that of native IPF via the inhibition of nuclear factor-κB (i.e., NF-κB), janus kinase-signal transducer and activator of transcription (i.e., JAK-STAT) signals and NLR family pyrin domain containing 3 (i.e., NLRP3) inflammasome activation. Moreover, a rabbit model of endotoxin induced uveitis evidences the superior therapeutic efficacy of the resulting hydrogel over that of clinically used 0.1 wt% diclofenac sodium eyedrop. Overall, this work offers new insights into the anti-inflammatory mechanism of PDCs hydrogel and presents the therapeutic values in the treatment of ocular disorders, and ultimately fulfils the potential clinical benefits of PDCs.
研究领域:
药学
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材料科学
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免疫学
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眼科学
✓ 已验证
DOI
高影响因子
Acta Pharmaceutica Sinica B
·
2023
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IF 14.5
Peng Hua,Ruifeng Liang,Yanbei Tu,Yuying Yin,Man-Kay Law,Meiwan Chen
Normalizing inflamed soils including reactive oxygen species (ROS), nitric oxide (NO), cell-free DNA, and regulating inflammation-related seeds such as macrophages, neutrophils, fibroblasts, represent a promising strategy to maintain synovial tissue homeostasis for rheumatoid arthritis (RA) treatment. Herein, ROS scavenging amphiphilic block copolymer PEGylated bilirubin and NO-scavenging PEGylated o-phenylenediamine were fabricated to self-assemble into a dually responsive nanoparticle loaded with JAK inhibitor notopterol ( [email protected] /oPDA-PEG, NBOP NPs). The simultaneous ROS and NO depletion combined with JAK-STAT pathway inhibition could not only promote M2 polarization to reduce further ROS and NO generation, but also decrease cytokines and chemokines to prevent immune cell recruitment. Specifically, NBOP NPs responded to high level ROS and NO, and disintegrated to release notopterol in inflamed joints as the hydrophobic heads BR and oPDA were transformed into hydrophilic ones. The released notopterol could inhibit the JAK-STAT pathway of inflammatory cells to reduce the secretion of pro-inflammatory cytokines and chemokines. This strategy represented an effective way to regulate RA soils and seeds through breaking the positive feedback loop of inflammation aggravation, achieving an excellent anti-RA efficacy in a collagen-induced arthritis rat model. Taken together, our work offered a reference to adjust RA soils and seeds for enhanced RA treatment.
研究领域:
纳米技术
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药理学
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风湿病学
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炎症生物学
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产品关联
DOI
PubMed
高影响因子
CURRENT MICROBIOLOGY
·
2025
·Vol. 82
·期 10
·1-12
·
IF 2.6
Bi Jinli,Huang Xin,Meng Liqin,Li Jinghan,He Yu,Jin Jing,Li Taijie
Hypervirulent Klebsiella pneumoniae (hvKP) possesses multiple virulence factors and causes severe infections with elevated mortality rates. It induces a strong inflammatory response in the host, with macrophages playing a key role in defense and inflammation. However, the signaling pathways of macrophages involved in response to hvKP infection remain unclear. In this study, we developed a stable hvKP infection model in differentiated THP-1 macrophages, confirmed by CFU assay and LDH cytotoxicity assay, and subsequently performed transcriptomic profiling analysis of hvKP-infected cells to characterize infection-induced gene expression changes. Pathway and differential gene correlation network analyses identified 14 potential regulatory genes primarily involved in inflammation. These changes in gene expression were further validated by Reverse transcription quantitative PCR (RT-qPCR). KEGG and GO analyses revealed several key signaling pathways involved in inflammation and immune response, particularly the TNF, IL-17, NF-κB, and JAK-STAT pathways. Further analysis indicated that the NF-κB signaling pathway plays a central role in the inflammatory response to hvKP infection, whereas the TNF and IL-17 pathways act synergistically to upregulate pro-inflammatory cytokines and chemokines. Western blot analysis confirmed the expression of TRAF6 and NF-κB p65 protein during hvKP infection. This study provides valuable insights into the molecular mechanisms of macrophage responses to hvKP, offering potential targets for therapeutic intervention.
研究领域:
微生物学
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免疫学
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分子生物学
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传染病学
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基因组学
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细胞生物学
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生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PeerJ
·
2024
·
IF 2.3
Junli Du,Chao Chen,Jie Chen
Background Cirsilineol is a trimethoxy and dihydroxy flavonoid isolated from plant species such as Artemisia vestita and has a variety of pharmacological properties. This study analyzed whether cirsilineol could prevent postoperative cognitive dysfunction (POCD). Methods A POCD mouse model induced by anesthesia/surgery induction and a cell model established with hydrogen peroxide (H 2 O 2 )-induced microglia BV-2 were employed to explore the efficacy of cirsilineol on POCD. The cognition function of the mice were assessed by carrying out behavioral tests (Morris water maze test and Y-maze test). We assessed the activation and polarization status of microglia using immunofluorescence analysis and detected the expression levels of CD86 and CD206 using the quantitative PCR (qPCR). Subsequently, cell viability was determined by CCK-8 assay and apoptosis was assessed using Calcein-AM/PI staining. Meanwhile, superoxide dismutase (SOD) and malondialdehyde (MDA) levels in plasma and cell culture medium were detected using chemiluminescence. Finally, the phosphorylation levels of JAK/STAT signaling pathway-related proteins were analyzed by Western blot. Results Cirsilineol reduced the escape latency and times of crossing island and increased spontaneous alternation (SA) rate, restoring the cognitive dysfunctions of POCD-modeled mice. Meanwhile, POCD elevated CD86 expression and malondialdehyde content and lowered the level of SOD; however, cirsilineol promoted CD206 expression and generation of SOD and inhibited malondialdehyde production. In H 2 O 2 -induced microglia BV-2, cirsilineol treatment increased SOD content and suppressed the generation of reactive oxygen species (ROS) and malondialdehyde, modulating microglia M1/M2 polarization and JAK/STAT pathway. Conclusion Cirsilineol prevented against POCD by attenuating oxidative stress and modulating microglia M1/M2 polarization, providing novel insights for the management of POCD.
研究领域:
药理学
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神经科学
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外科手术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Toxicology Research
·
2021
·Vol. 10
·期 5
·1013-1021
·
IF 3.524
Liu Yan-ping,Cai Ying,Lei Yuan-di,Yuan Xiao-yan,Wang Ye,Yi Shan,Li Xun-ya,Huang Lian,Long Ding-xin,Zhang Zhao-hui
Circular RNAs (circRNAs), is a novel type of endogenous non-coding RNAs (ncRNAs) participated in the pathogenesis of many diseases. Beryllium is one of the carcinogenesis elements. However, the mechanism and function of circRNAs in human bronchial epithelial cells (16HBE) induced by beryllium sulfate (BeSO4) was rarely reported. Therefore, the high-throughput RNA sequencing analysis was performed to detect the circRNA profiles between control groups and BeSO4-induced groups. Furthermore, circRNA-miRNA-mRNA network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and PPI network analysis were used for bioinformatics analysis. CircRNA sequencing analysis revealed that 36 circRNAs were up-regulated and 35 circRNAs were down-regulated in the BeSO4-exposed groups. The selected circRNAs were verified by real-time fluorescent quantitative PCR (qRT-PCR). Hsa_circ_0004214 and hsa_circ_0003586 were validated to be up-regulated, hsa_circ_0047958, hsa_circ_0001944, and hsa_circ_0008982 were down-regulated. The circRNA-miRNA-mRNA network annotated the key signaling pathway including cellular senescence, TNF signaling pathway, NF-kappa B signaling pathway, HIF-1 signaling pathway, and Hippo signaling pathway. The PPI network indicated the most circRNAs might participate in the BeSO4 toxicity by acting as a sponge for the miR-663b through JAK–STAT signaling pathway. In summary, our study suggests that circRNAs may play roles in the mechanism of beryllium toxicity.
研究领域:
分子生物学
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毒理学
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生物信息学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2021
·Vol. 17
·期 13
·2007391
·
IF 13.281
Xueqi Li,Jianwei Li,Jiarui Xu,Kun Chen,Zhan Zhang,Jialun Duan,Qian Luo,Yafei Du,Songyue Chen,Ying Xie,Wanliang Lu
Breast cancer is the most common malignant disease in women all over the world and its chemotherapy outcome is restricted by multidrug resistance. Here, a nanostructure by functional larotaxel liposomes decorated with guanine-rich quadruplex nucleotide-lipid derivative for treatment of resistant breast cancer is developed. The studies are performed on the resistant breast cancer cells and the cancer-bearing mice. The nucleotide–lipid derivative (DSPE-PEG 2000 -C 6 -GT28nt) is synthesized by introducing a hydrophobic hexyl linkage between GT-28nt (containing 17 guanines and 11 thymidines) and DSPE-PEG 2000 -NHS, and is incorporated on the functional larotaxel liposomes for specific binding with nucleolin receptor on the resistant cancer cells. The studies demonstrate that the liposomes had long circulatory effect, targeted capability, and significant anticancer efficacy in resistant cancer-bearing mice. The studies further reveal their action mechanism, consisting of blocking depolymerization of microtubules, arresting cell cycle, blocking JAK-STAT signaling pathway, and inhibiting activity of antiapoptotic proteins. In conclusion, the functional larotaxel liposomes can be used for effective treatment of drug-resistant breast cancer, and this study also offers a novel targeted nanomedicine based on nucleotide–lipid derivative.
研究领域:
药理学
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纳米技术
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肿瘤学
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分子生物学
·
化疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2019
·
IF 5.589
Xia Wang,Jianbo Zhu,Baida Kong,Bingnan He,Lai Wei,Yuanxiang Jin,Yudong Shan,Weitao Wang,Chunqiang Pan,Zhengwei Fu
Short-chain chlorinated paraffins (SCCPs, C 10–13 ) were listed as persistent organic pollutants (POPs) by the Stockholm Convention in 2017 and pose extensive exposure risks to humans. To our knowledge, there have been no studies reporting the immmunomodulatory effects of SCCPs until now. C 9 -CPs have also been shown to be present in the environment. In this study, adult male C57BL/6 mice were exposed to 1, 10, or 100 mg/kg/d C 9–13 -CPs by gavage for 28 d. The results showed that compared to those of the controls, exposure to C 9–13 -CPs led to increased spleen weight, delimited germinal centers, enhanced energy metabolism, and elevated glutathione content, but no variation in the malonaldehyde level in the spleen was observed. Exposure to C 9–13 -CPs also increased the populations of splenic lymphocytes, T lymphocytes, NK cells, and the ratio of the CD3 + /CD19 + subsets and CD4 + /CD8 + subsets compared to those of the controls. RNA-seq revealed 424 differentially expressed genes (DEGs) (fold change ≥ 1.5, FDR < 0.05) in the spleen between the control group and the 100 mg/kg/d C 9–13 -CPs-treated group. KEGG analysis demonstrated that folate biosynthesis, pathways in cancer and thyroid hormone signaling were the three most significantly enriched pathways, and despite not reaching statistical significance, some immune-related pathways were also enriched in the KEGG functional enrichment analysis, including the chemokine signaling pathway (FDR < 0.0584), the NF-κB signaling pathway (FDR < 0.0663), Th17 cell differentiation (FDR < 0.0839), and the Jak-STAT signaling pathway. Moreover, compared to those of the controls, exposure to C 9–13 -CPs enhanced the Concanavalin A (Con A)-stimulated cultured splenocyte proliferation, while the exposure showed no effect on the splenocyte proliferation that was stimulated by lipopolysaccharides (LPS). Taken together, these results demonstrated that subacute exposure to C 9–13 -CPs could have immunomodulatory effects in mice. The present study helps to provide an understanding of the comprehensive health risks posed by C 9–13 -CPs.
研究领域:
毒理学
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免疫学
·
分子生物学
·
环境科学
✓ 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）