ORAL DISEASES
·
2024
·
IF 2.9
Yifei Deng,Junhong Xiao,Xin Huang,Zhengguo Cao
Objective Inflammatory stimuli compromise the differentiation potency of human periodontal ligament cells (hPDLCs). Macrophage-derived exosomes (M-Exo) play a role in several aspects of cellular activity. This study investigated how M-Exo contributes to the osteo-/cementogenic differentiation of hPDLCs under inflammation and the mechanism involved. Methods M-Exo was identified by transmission electron microscopy, western blotting (WB), and dynamic light scattering. The internalization of M-Exo by hPDLCs was observed. After M-Exo treatment, the osteo-/cementogenic markers were detected by RT-qPCR and WB, and alkaline phosphatase (ALP) activity by ALP staining. Tumor necrosis factor alpha (TNF-ɑ) was applied to simulate inflammation. The rescue effect of M-Exo on TNF-ɑ-suppressed differentiation was validated. The p38 MAPK pathway activity was tested and a specific inhibitor was applied to explore the mechanism. Results M-Exo was successfully isolated, identified and internalized by hPDLCs. M-Exo enhanced the osteo-/cementogenic differentiation of hPDLCs, as indicated by upregulated osteo-/cementogenic markers and elevated ALP activity. Moreover, TNF-ɑ inhibited the differentiation capabilities of hPDLCs, on which M-Exo showed a rescue effect. M-Exo activated the p38 MAPK pathway and SB203580 attenuated its promotion effect. Conclusion This study showed that M-Exo ameliorated the TNF-ɑ-suppressed osteo-/cementogenic differentiation of hPDLCs partly through the p38 MAPK pathway.
研究领域:
牙科研究
·
细胞生物学
·
炎症
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROGASTROENTEROLOGY AND MOTILITY
·
2019
·Vol. 31
·期 6
·e13555
·
IF 3.803
Mengjuan Lin,Lei Chen,Yong Xiao,Baoping Yu
Background Irritable bowel syndrome (IBS) is a common disease with intestinal dysmotility, whose mechanism remains elusive. The endocannabinoid system is emerging as an important modulator of gastrointestinal (GI) motility in multiple diseases, but its involvement in IBS is unknown. We aimed to determine whether cannabinoid 2 (CB2) receptor modulates intestinal motility associated with stress-induced IBS. Methods A rat IBS model was established by chronic water avoidance stress (WAS). Colonic pathological alterations were detected histologically and intestinal motility was assessed by intestinal transit time (ITT) and fecal water content (FWC). Visceral sensitivity was determined by visceromotor response (VMR) to colorectal distension (CRD). Real-time PCR, western blot, and immunostaining were performed to identify colonic CB2 receptor expression. Colonic muscle strip contractility was studied by isometric transducers and nitric oxide (NO) was detected by the Griess test. The effects of AM1241, a selective agonist of CB2 receptors, on colonic motility were examined. Key Results After 10 days of WAS exposure, ITT was decreased and FWC elevated while VMR magnitude in response to CRD was significantly enhanced. Colon CB2 protein and mRNA levels increased and density of CB2-positive macrophages in the mucosa and enteric neurons in the myenteric plexus was higher than in controls. Pharmacological enhancement of CB2 activity by AM1241 relieved colonic hypermotility in WAS rats in a concentration-dependent manner via inhibition of p38 phosphorylation and elevation of NO production. Conclusion CB2 receptor may exert an important inhibitory effect in stress-induced colonic hypermotility by modulating NO synthesis through p38 mitogen-activated protein kinase signaling. AM1241 could be used as a potential drug to treat disorders with colonic hypermotility.
研究领域:
胃肠病学
·
药理学
·
神经胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Xiaojie Yan,Xueying Zhao,Mingde Fan,Wenfu Zheng,Guanxiong Zhu,Bin Li,Le Wang
Background Dihydroartemisinin (DHA) has emerged as a promising candidate for anticancer therapy. However, the application of DHA in clinics has been hampered by several limitations including poor bioavailability, short circulation life, and low solubility, significantly restricting its therapeutic efficacy and leading to notable side effects during the treatment.Purpose We present DHA-loaded zeolitic imidazolate framework-8 (D-ZIF) with controllable and targeted DHA release properties, leading to enhanced antitumor effects while reducing potential side effects.Methods D-ZIF was prepared by one-pot synthesis method using methylimidazole (MIM), Zn(NO3)2•6H2O and DHA. We characterized the physical and chemical properties of D-ZIF by TEM, DLS, XRD, FT-IR, and TG. We measured the drug loading efficiency and the cumulative release of DHA in different pH conditions. We evaluated the cytotoxicity of D-ZIF on renal cell carcinoma (RCC786-O), glioma cells (U251), TAX-resistant human lung adenocarcinoma (A549-TAX) cells by CCK8 in vitro. We explored the possible antitumor mechanism of D-ZIF by Western blot. We evaluated the biocompatibility and hemolysis of D-ZIF and explored the in vivo antitumor efficiency in mice model by TUNEL testing and blood biomarker evaluations.Results D-ZIF showed rhombic dodecahedral morphology with size of 129±7.2 nm and possessed a noticeable DHA encapsulation efficiency (72.9%). After 48 hours, D-ZIF released a cumulative 70.0% of the loaded DHA at pH 6.5, and only 42.1% at pH 7.4. The pH-triggered programmed release behavior of D-ZIF could enhance anticancer effect of DHA while minimizing side effects under normal physiological conditions. Compared with the free DHA group with 31.75% of A549-TAX cell apoptosis, the percentage of apoptotic cells was approximately 76.67% in the D-ZIF group. D-ZIF inhibited tumor growth by inducing tumor cell apoptosis through the mechanism of ROS production and regulation of Nrf2/HO-1 and P38 MAPK signaling pathways. D-ZIF showed potent effects in treating tumors with high safety in vivo.Conclusion This pH-responsive release mechanism enhanced the targeting efficiency of DHA towards tumor cells, thereby increasing drug concentration in tumor sites with negligible side effects. Herein, D-ZIF holds great promise for curing cancers with minimal adverse effects.
研究领域:
药学
·
癌症研究
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2023
·Vol. 30
·期 36
·85578-85591
·
IF 5.8
Tang Jielin,Qin Jinyan,Kuerban Guzailinuer,Li Jiayi,Zhou Qinyu,Zhang Hongdan,Sun Rongli,Yin Lihong,Pu Yuepu,Zhang Juan
As an emerging flame retardant, organic phosphate flame retardants have been extensively used worldwide. The aim of this study is to determine the effects of TnBP on neurobehavior of Caenorhabditis elegans ( C. elegans ) and its mechanisms. L1 larvae of wild-type nematodes (N2) were exposed to TnBP of 0, 0.1, 1, 10, and 20 mg/L for 72 hours. Then, we observed that the body length and body width were inhibited, the head swings were increased, the pump contractions and chemical trend index were reduced, the production of reactive oxygen species (ROS) was increased, and the expression of mitochondrial oxidative stress related genes ( mev-1 and gas-1 ) and P38 MAPK signal pathway-related genes ( pmk-1 , sek-1 , and nsy-1 ) was altered. After reporter gene strains BZ555, DA1240, and EG1285 were exposed to TnBP of 0, 0.1, 1, 10, and 20 mg/L for 72 hours, the synthesis of dopamine, glutamate, and Gamma-Amino Butyric Acid (GABA) was increased. In addition, the pmk-1 mutants (KU25) led to the sensitivity of C. elegans to TnBP in terms of head swings. The results showed that TnBP had harmful effects on the neurobehavior of C. elegans , oxidative stress might be one of the mechanisms of its neurotoxicity, and P38 MAPK signal pathway might play an important regulatory role in this process. The results revealed the potential adverse effects of TnBP on the neurobehavior of C. elegans .
研究领域:
毒理学
·
神经科学
·
环境科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2026
·
IF 6.1
Yu Liao,Weipeng Wei,Fuli Qin,Yusheng Ruan,Ting He,Jiansong He,Mingchao Wang,Taotao Liu,Jiemei Chen
Background: Current ulcerative colitis (UC) therapies often cause adverse effects, and novel treatments are urgently needed. Cordycepin (COR), a bioactive compound from Cordyceps militaris, shows anti-inflammatory and intestinal protective potential, its precise role and mechanisms in UC remain unclear.Purpose: This study aimed to elucidate the effects and underlying mechanisms of COR on UC.Methods: Using dextran sulfate sodium (DSS)-induced acute colitis mice and DSS-damaged human colonic epithelial cells as models, we evaluated and analyzed the effects and mechanisms of COR on UC by combining molecular docking, molecular dynamics simulations, in vivo/in vitro interventions with selective pharmacological antagonists, transcriptome sequencing and Western blotting verification.Results: In vitro experiments confirmed that COR exhibits protective effects on DSS-damaged colonic epithelial cells. Mechanistic studies revealed that COR elevates intracellular cAMP levels, and the selective adenosine A2A receptor (A2AAR) antagonist SCH58261 can block the protective effect of COR. Molecular docking and dynamics simulation analyses also demonstrated an interaction between COR and A2AAR at the molecular level. In vivo experiments further verified that oral administration of COR (5 mg/kg, 10 mg/kg) significantly ameliorated DSS-induced colitis in mice, manifested by reduced disease activity index, attenuated weight loss, improved colon shortening, decreased serum pro-inflammatory cytokines, alleviated colonic inflammation, and restored intestinal barrier function. Moreover, the therapeutic effect of COR on colitis could be blocked by SCH58261. Further investigations indicated that COR inhibits IL-6/IL-6R signaling in colonic tissues and suppresses phosphorylation-mediated activation of p38 MAPK and NF-κB p65 through A2AAR activation.Conclusion: COR ameliorates DSS-induced colitis by activating A2AAR to upregulate cAMP levels, inhibiting IL-6/IL-6R-mediated p38 MAPK and NF-κB activation. This study confirms A2AAR as a key therapeutic target, providing data support for the potential application of COR in UC treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Shaoyin Wei,Zeyu Shou,Dong Yang,Linxiao Sun,Yan Guo,Yang Wang,Xingjie Zan,Lianxin Li,Chunwu Zhang
Osteoarthritis (OA) is a common chronic inflammatory disease that leads to disability and death. Existing therapeutic agents often require frequent use, which can lead to drug resistance and long-term side effects. Polyphenols have anti-inflammatory and antioxidant potential. However, they are limited by their short half-life and low bioavailability. This work presents a novel pure polyphenol capsule for sustained release of polyphenols, which is self-assembled via hydrophobic and hydrogen bonds. The capsule enhances cellular uptake, scavenges reactive oxygen and nitrogen species, reduces inflammatory markers, and remodels the OA microenvironment by inhibiting the p38 MAPK pathway. The capsule overcomes the limitations of short half-life and low bioavailability of polyphenols and achieves single-dose cure in mouse and dog OA models, providing an optimal therapeutic window for OA repair. Taking advantage of simple manufacturing, convenient administration, and pure polyphenol composition, these capsules show great potential for clinical treatment of osteoarthritis and chronic inflammatory diseases.
研究领域:
药理学
·
风湿病学
·
生物医学工程
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 13
·期 3
·1393-1407
·
IF 5.396
Liuming Xie,Zhibing Huang,Hui Meng,Zhibing Fan,Xiaoyi Shi,Jianhua Xie
Manipulating the structures, physicochemical properties, and monosaccharide compositions of exopolysaccharides (EPS) isolated from microorganisms has been reported to enhance their biological activities. Hence, the aim of this work was to examine the effects of genistein addition during fermentation on the amount, physicochemical properties, and immunomodulatory activity of EPS secreted by M. purpureus. Results showed that genistein addition significantly increased M. purpureus biomass and EPS yield to 2.42 g L−1 and 6.08 g L−1, respectively, and affected the physicochemical properties and structures of EPS. Furthermore, EPS produced by genistein-treated M. purpureus (G-EMP) improved the immunomodulatory activity of RAW264.7 macrophages by increasing the secretion of nitric oxide and cytokines. Moreover, phospho-Jun N-terminal kinase (p-JNK), phospho-extracellular regulated protein kinase (p-ERK), phospho-p38 (p-p38) mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) phospho-p65 (p65) proteins were remarkably upregulated by G-EMP stimulation, blocking Toll-like receptor 4 (TLR4) that dramatically reduced the pinocytic and phagocytic capacities. Overall, these findings provide potential rationales for the application of genistein in improving the EPS yield of M. purpureus.
研究领域:
微生物学
·
免疫学
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RESPIRATORY RESEARCH
·
2023
·Vol. 24
·期 1
·1-18
·
IF 5.8
Wu Zhuhua,Zhu Li,Nie Xinran,Liu Yingli,Zhang Xiaoju,Qi Yong
Background Obesity has been identified as a risk factor for acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, the underlying mechanisms remain elusive. This study aimed to investigate the role of fatty acid synthase (FASN) in lipopolysaccharide (LPS)-induced ALI under obesity. Methods A high-fat diet-induced obese (DIO) mouse model was established and lean mice fed with regular chow diet were served as controls. LPS was intratracheally instilled to reproduce ALI in mice. In vitro, primary mouse lung endothelial cells (MLECs), treated by palmitic acid (PA) or co-cultured with 3T3-L1 adipocytes, were exposed to LPS. Chemical inhibitor C75 or shRNA targeting FASN was used for in vivo and in vitro loss-of-function studies for FASN. Results After LPS instillation, the protein levels of FASN in freshly isolated lung endothelial cells from DIO mice were significantly higher than those from lean mice. MLECs undergoing metabolic stress exhibited increased levels of FASN, decreased levels of VE-cadherin with increased p38 MAPK phosphorylation and NLRP3 expression, mitochondrial dysfunction, and impaired endothelial barrier compared with the control MLECs when exposed to LPS. However, these effects were attenuated by FASN inhibition with C75 or corresponding shRNA. In vivo, LPS-induced ALI, C75 pretreatment remarkably alleviated LPS-induced overproduction of lung inflammatory cytokines TNF-α, IL-6, and IL-1β, and lung vascular hyperpermeability in DIO mice as evidenced by increased VE-cadherin expression in lung endothelial cells and decreased lung vascular leakage. Conclusions Taken together, FASN inhibition alleviated the exacerbation of LPS-induced lung injury under obesity via rescuing lung endothelial dysfunction. Therefore, targeting FASN may be a potential therapeutic target for ameliorating LPS-induced ALI in obese individuals.
研究领域:
药理学
·
免疫学
·
肺科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-33
·
IF 10.6
Liu Jianyu,Wang Meiqun,Tian Xiaoyan,Wu Shuhong,Peng Haisen,Zhu Yaqiong,Liu Yuehui
Allergic rhinitis (AR) is a condition with limited treatment options. This study investigates the potential use of mesenchymal stem cell (MSC) nanovesicles as a novel therapy for AR. Specifically, the study explores the underlying mechanisms of MSC nanovesicle therapy by targeting dendritic cells (DCs). The researchers fabricated DC-targeted P-D2-EVs nanovesicles and characterized their properties. Transcriptomic sequencing and single-cell sequencing analyses were performed to study the impact of P-D2-EVs on AR mice, identifying core genes involved in the treatment. In vitro cell experiments were conducted to validate the effects of P-D2-EVs on DC metabolism, Th2 differentiation, and ILC2 activation. The results showed that P-D2-EVs efficiently targeted DCs. Transcriptomic sequencing analysis revealed differential expression of 948 genes in nasal tissue DCs of mice treated with P-D2-EVs. Single-cell sequencing further revealed that P-D2-EVs had inhibitory effects on DC activation, Th2 differentiation, and ILC2 activation, with Fut1 identified as the core gene. Validation experiments demonstrated that P-D2-EVs improved IL10 metabolism in DCs by downregulating Fut1 expression, thereby suppressing Th2 differentiation and ILC2 activation. Animal experiments confirmed the inhibitory effects of P-D2-EVs and their ability to ameliorate AR symptoms in mice. The study suggests that P-D2-EVs reshape DC metabolism and suppress Th2 differentiation and ILC2 activation through the inhibition of the Fut1/ICAM1/P38 MAPK signaling pathway, providing a potential therapeutic approach for AR. Graphical Abstract
研究领域:
免疫学
·
分子生物学
·
细胞生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Pharmaceuticals
·
2024
·Vol. 17
·期 6
·805
·
IF 4.3
Tian-Qu He,Zhi Wang,Chuang-Ye Li,Yao-Wang Zhao,Xin-Yi Tong,Jing-Hong Liu,Jian-Ming Ouyang
Purpose:Adhesion between calcium oxalate crystals and renal tubular epithelial cells is a vital cause of renal stone formation; however, the drugs that inhibit crystal adhesion and the mechanism of inhibition have yet to be explored.Methods:The cell injury model was constructed using nano-COM crystals, and changes in oxidative stress levels, endoplasmic reticulum (ER) stress levels, downstream p38 MAPK protein expression, apoptosis, adhesion protein osteopontin expression, and cell–crystal adhesion were examined in the presence ofLaminarinpolysaccharide (DLP) and sulfated DLP (SDLP) under protected and unprotected conditions.Results:Both DLP and SDLP inhibited nano-COM damage to human kidney proximal tubular epithelial cell (HK-2), increased cell viability, decreased ROS levels, reduced the opening of mitochondrial membrane permeability transition pore, markedly reduced ER Ca2+ion concentration and adhesion molecule OPN expression, down-regulated the expression of ER stress signature proteins including CHOP, Caspase 12, and p38 MAPK, and decreased the apoptosis rate of cells. SDLP has a better protective effect on cells than DLP.Conclusions:SDLP protects HK-2 cells from nano-COM crystal-induced apoptosis by reducing oxidative and ER stress levels and their downstream factors, thereby reducing crystal–cell adhesion interactions and the risks of kidney stone formation.
研究领域:
药理学
·
泌尿学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Yulin Qi,Lu Liu,Dan Liang,Shiyun Tang,Xiaoyi Yu,Hejiang Ye,Nianzhi Chen
Background Retinitis pigmentosa (RP) refers to a group of progressive photoreceptor degenerative diseases . The activation of microglia has been reported to play an important role in the photoreceptor degeneration in RP retinal. Bujing Yishi tablets (BJYS), a Chinese herbal medicine , has been used to treat retinal diseases in China with desirable effect in improving visual function. However, the mechanisms underlying the efficacy of BJYS treatment in RP are not yet fully understood. Purpose Based on the preliminary experiments, this study aimed to investigate the therapeutic mechanism involved in treating N -Methyl- N -Nitrosourea (MNU)-induced retinal degeneration of RP with BJYS. Methods To explore the efficacy of BJYS, a rat experimental RP model was established through intraperitoneal injection of MNU (50 mg/kg). Two experiment was carried out. After the treatment, we conducted H&E, TUNEL , retinal cytokine levels and IBA-1 expression in microglia to confirm the impact on RP model. The specific mechanism of action of BJYS tablet was assessed by western blot , real-time polymerase chain reaction (RT-PCR), and immunofluorescence to determine the mRNA and protein expression levels involved in clarifying the effectiveness of BJYS exerted through P2X7R/CX3CL1/CX3CR1 pathway. Results Significant alleviation of retinal morphological structure and photoreceptor degeneration by BJYS treatment was observed in the retinal of MNU-induced RP rats, BJYS prevented the reduction of ONL thickness and decreased the level of apoptotic cells in ONL. It also inhibited microglia overactivation and reduced retinal levels of IL-1β, IL-6, TNF-α. In addition, BJYS decreased the protein expression and mRNA expression of P2X7, CX3CL1 and CX3CR1 and reduced the phosphorylation of p38 MAPK . Conclusion In summary, this study suggested that BJYS treatment could alleviate photoreceptors degeneration of RP by inhibiting microglia overactivation and inflammation through the P2X7R/CX3CL1/CX3CR1 pathway. These effects suggest that BJYS tablets may serve as a promising oral therapeutic agent for RP.
研究领域:
眼科学
·
药理学
·
神经科学
·
中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2024
·
IF 10.7
Yingqi Chen,Zuocheng Qiu,Xueling Hu,Tiehua Wang,Guoqing Li,Ziling Tang,Chongzhou Fang,Weibei Sheng,Jin Zhao,Fei Yu,Jian Weng,Anjaneyulu Udduttula,Geetha Manivasagam,Hui Zeng
In clinical settings, regenerating critical-sized calvarial bone defects presents substantial problems owing to the intricacy of surgical methods, restricted bone growth medications, and a scarcity of commercial bone grafts. To treat this life-threatening issue, improved biofunctional grafts capable of properly healing critical-sized bone defects are required. In this study, we effectively created anti-fracture hydrogel systems using spongy-like metal-organic (magnesium-phosphate) coordinated chitosan-modified injectable hydrogels (CPMg) loaded with a bioinspired neobavaisoflavone (NBF) component. The CPMg-NBF hydrogels showed outstanding anti-fracture capabilities during compression testing and retained exceptional mechanical stability even after 28 d of immersion in phosphate-buffered saline. They also demonstrated prolonged and stable release profiles of Mg 2+ and NBF. Importantly, CPMg-NBF hydrogels revealed robust biphasic mineralization and were non-toxic to MC3T3-E1 cells. To better understand the underlying mechanism of Mg 2+ and NBF component, as well as their synergistic effect on osteogenesis, we investigated the expression of key osteogenic proteins in the p38 MAPK and NOTCH pathways. Our results showed that CPMg-NBF hydrogels greatly increased the expression of osteogenic proteins (Runx2, OCN, OPN, BMPS and ALP). In vivo experiments showed that the implantation of CPMg-NBF hydrogels resulted in a significant increase in new bone growth within critical-sized calvarial defects. Based on these findings, we expect that the CPMg-NBF supramolecular hydrogel has tremendous promise for use as a therapeutic biomaterial for treating critical-sized calvarial defects.
研究领域:
生物材料
·
组织工程
·
骨科
·
生物医学工程
·
药学
✓ 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）