FOOD AND CHEMICAL TOXICOLOGY
·
2014
·
IF 2.61
Xiaokang Zhu,Mingdong Jiang,Erqun Song,Xiaoji Jiang,Yang Song
Ultraviolet B (UVB) radiation causes oxidative damage and inflammation, and ultimately increases the risk of skin carcinogenesis. Selenium is an essential trace element, previous studies indicated selenium deficiency impairs tissue antioxidant capacity in different experimental models. However, the synergistic effect of selenium deficiency and UVB radiation on skin damage is not clear. In the current study, our data revealed selenium deficiency resulted in further increases of reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS) and phosphorylated H2AX levels, decreases of GSH level and antioxidant enzyme activities in UVB-irradiated mice. Selenium deficiency also exacerbated UVB-induced cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 mRNA expressions. Mechanism studies indicated that UVB-induced p38 signaling was further elevated in the skin of mice maintained with selenium deficiency diet, compared with those maintained with selenium adequate diet. Our investigation suggested that selenium deficiency diet weakens the antioxidant capacity of UVB-irradiated mice skin, which sensitizes to UV radiation-induced oxidative damage and inflammation.
研究领域:
皮肤病学
·
分子生物学
·
营养学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Qixuan He,Anquan Ma,Ziqing Yang,Xinyu Pang,Chen Li,Jiayong Diao,Yuxuan Liu,Quanzhen Liu,Qingyue Zhang,Zuoqing Dong,Dongjiao Zhang
Background Bisphenol A (BPA), an environmental pollutant, has been implicated in oral squamous cell carcinoma (OSCC) progression, yet its molecular mechanisms remain unclear. This study explores the role of GABBR1 in BPA-induced OSCC malignancy. Methods Bioinformatics analysis identified GABBR1 as a key gene in OSCC. Expression patterns and clinical relevance were assessed using TCGA, GTEx, and HPA databases. Molecular docking and dynamics simulations further elucidated the binding interaction between BPA and GABBR1. Functional assays, including western blot, immunofluorescence, CCK-8, EdU, and transwell evaluated the effects of BPA exposure and GABBR1 knockdown on OSCC cell function. Transwell co-culture, RT-PCR and ELISA assays examined exosome-mediated interactions between OSCC cells and macrophages. Results BPA exposure enhanced OSCC proliferation, migration, and invasion while promoting stemness through the GABBR1/MEK/ERK signaling pathway. Additionally, it induced M2 macrophage polarization via exosomal communication, contributing to an immunosuppressive microenvironment. Conclusion This study uncovers a novel mechanism by which BPA promotes OSCC progression via GABBR1-mediated signaling and exosome-driven immunomodulation, highlighting GABBR1 as a potential therapeutic target in BPA-associated OSCC.
研究领域:
肿瘤学
·
分子生物学
·
免疫学
·
环境毒理学
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2017
·Vol. 14
·期 6
·5445-5451
·
IF 1.261
Jianxin Zhang,Fengchun Wang,Huali Wang,Yanna Wang,Yan Wu,Hui Xu,Chen Su
Paeoniflorin (PAE), a principal bioactive component of Paeonia lactiflora Pall., appears to have antitumor properties. However, the pharmacological activity of PAE in endometrial cancer and the specific mechanisms have remained largely elusive. The present study aimed to determine the antitumor activity of PAE in the human endometrial cancer cell line RL95‑2 and explore the potential mechanisms. Cell proliferation was assessed to evaluate the antitumor effect of PAE towards RL95‑2 cells via a Cell Counting Kit‑8 assay. Protein expression was examined to investigate changes in the signaling pathways of p38 mitogen‑activated protein kinase (MAPK), c‑Jun N‑terminal kinase (JNK), extracellular signal‑regulated kinase (ERK) and nuclear factor (NF)‑κB in RL95‑2 cells during PAE treatment by western blot analysis. The results revealed that PAE significantly and dose‑ and time‑dependently inhibited the proliferation of RL95‑2 cells. In addition, PAE activated MAPK signaling pathways (p38, JNK and ERK) and the NF‑κB signaling pathway. Furthermore, p38 MAPK and NF‑κB inhibitors (SB203580 and MG‑132, respectively) prevented PAE‑induced proliferative inhibition in RL95‑2 cells. However, ERK and JNK inhibitors (PD98059 and BI‑78D3, respectively) did not produce such an inhibition. In conclusion, the present study demonstrated that PAE exerts its anti‑proliferative activity via activating p38 MAPK and NF‑κB signaling pathways in endometrial cancer cells, providing a potential new drug of choice for endometrial cancer therapy.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Marine Drugs
·
2022
·Vol. 20
·期 2
·110
·
IF 6.085
Chunlei Li,Sirui Zhang,Jianhua Zhu,Weijuan Huang,Yuanyuan Luo,Hui Shi,Dongbo Yu,Liguo Chen,Liyan Song,Rongmin Yu
Colorectal carcinoma (CRC) is one of the major causes of cancer-related incidence and deaths. Here, we identified a novel antitumor peptide, P6, with a molecular weight of 2794.8 Da from a marine Chinese medicine,Arca inflataReeve. The full amino acid sequence and secondary structure of P6 were determined by tandem mass de novo sequencing and circular dichroism spectroscopy, respectively. P6 markedly inhibited cell proliferation and colony formation, and induced apoptosis in CRC cells. Mechanistically, transcriptomics analysis and a serial functional evaluation showed that P6 induced colon cancer cell apoptosis through the activation of the p38-MAPK signaling pathway. Moreover, it was demonstrated that P6 exhibited antitumor effects in a tumor xenograft model, and induced cell cycle arrest in CRC cells in a concentration-dependent mode. These findings provide the first line of indication that P6 could be a potential therapeutic agent for CRC treatment.Keywords:Arca inflata;antitumor peptide;apoptosis;MAPK signaling;calmodulin;colorectal cancer
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Peizhi Jia,Daxin Chen,Ying Zhu,Meiling Wang,Jianwei Zeng,Ling Zhang,Qiaoyan Cai,Dawei Lian,Chunyu Zhao,Yaoyao Xu,Jianfeng Chu,Shan Lin,Jun Peng,Wei Lin
Ethnopharmacological relevance Liensinine(Lien, C 37 H 42 N 2 O 6 ) is an alkaloid compound from plumula nelumbinis that demonstrates an antihypertensive effect. The protective effects of Lien on target organs during hypertension are still unclear. Aim of the study : This study aimed to understand the mechanism of Lien during the treatment of hypertension, with emphasis on vascular protection. Materials and methods Lien was extracted and isolated from plumula nelumbinis for further study. In vivo model of Ang II-induced hypertension, non-invasive sphygmomanometer was used to detect the blood pressure in and out of the context of Lien intervention. Ultrasound was used to detect the abdominal aorta pulse wave and media thickness of hypertensive mice, and RNA sequencing was used to detect the differential genes and pathways of blood vessels. The intersection of Lien and MAPK protein molecules was detected by molecular interconnecting technique. The pathological conditions of abdominal aorta vessels of mice were observed by HE staining. The expression of PCNA, α-SMA, Collagen Type Ⅰ and Collagen Type Ⅲ proteins were detected by IHC. The collagen expression in the abdominal aorta was detected by Sirius red staining. The MAPK/TGF-β1/Smad2/3 signaling and the protein expression of PCNA and α-SMA was detected by Western blot. In vitro , MAPK/TGF-β1/Smad2/3 signaling and the protein expression of PCNA and α-SMA were detected by Western blot, and the expression of α-SMA was detected by immunofluorescence; ELISA was used to detect the effect of ERK/MAPK inhibitor PD98059 on Ang Ⅱ-induced TGF-β1secrete; and the detection TGF-β1and α-SMA protein expression by Western blot; Western blot was used to detect the effect of ERK/MAPK stimulant12-O-tetradecanoyl phorbol-13-acetate (TPA) on the protein expression of TGF-β1 and α-SMA. Results Lien displayed an antihypertensive effect on Ang Ⅱ-induced hypertension, reducing the pulse wave conduction velocity of the abdominal aorta and the thickness of the abdominal aorta vessel wall, ultimately improving the pathological state of blood vessels. RNA sequencing further indicated that the differential pathways expressed in the abdominal aorta of hypertensive mice were enriched in proliferation-related markers compared with the Control group. The profile of differentially expressed pathways was ultimately reversed by Lien. Particularly, MAPK protein demonstrated good binding with the Lien molecule. In vivo, Lien inhibited Ang Ⅱ-induced abdominal aorta wall thickening, reduced collagen deposition in the ventral aortic vessel, and prevented the occurrence of vascular remodeling by inhibiting MAPK/TGF-β1/Smad2/3 signaling activation. In addition, Lien inhibited the activation of Ang II-induced MAPK and TGF-β1/Smad2/3 signaling, attenuating the expression of PCNA and inhibiting the reduction of α-SMA, collectively playing a role in the inhibition of Ang Ⅱ-induced hypertensive vascular remodeling. PD98059 alone could inhibit Ang Ⅱ-induced elevation of TGF-β1 and the decrease of α-SMA expression. Further, PD98059 combined with Lien had no discrepancy with the inhibitors alone. Simultaneously TPA alone could significantly increase the expression of TGF-β1 and decrease the expression of α-SMA. Further, Lien could inhibit the effect of TPA. Conclusion This study helped clarify the protective mechanism of Lien during hypertension, elucidating its role as an inhibitor of vascular remodeling and providing an experimental basis for the research and development of novel antihypertensive therapies.
研究领域:
药理学
·
心血管疾病
·
分子生物学
·
民族药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2024
·
IF 3.3
Jun-qi Zhan,Jun-xin Wu,Jing-jing Fu,Gao-shang Li,Fang Wu,Yue-wen Chen
BACKGROUND Giant salamander protein peptide is a peptide with rich functional properties. Giant salamander protein peptide KGEYNK (KK-6) is a peptide with both antioxidant and anti-inflammatory properties. The antioxidant and anti-inflammatory mechanisms of KK-6 are still unclear. When we studied the functional mechanism of KK-6, we found that the antioxidant property of KK-6 has a synergistic and promoting effect on anti-inflammatory properties. RESULTS KK-6 enhances cellular resistance to LPS via the MAPK/NF-κB signaling pathway, leading to increased levels of inflammatory factors: interleukin-1β (764.81 ng mL −1 ), interleukin-6 (1.06 ng mL −1 ) and tumor necrosis factor-α (4440.45 ng mL −1 ). KK-6 demonstrates potent antioxidant properties by activating the Nrf2 signaling pathway, resulting in elevated levels of antioxidant enzymes (glutathione peroxidase: 0.03 μg mL −1 ; superoxide dismutase: 0.589 μg mL −1 ) and a reduction in the concentration of the oxidative product malondialdehyde (967.05 μg mL −1 ). CONCLUSION Our findings highlight the great potential of KK-6, a peptide extracted from giant salamander protein, as a remedy for intestinal inflammation. Through its dual role as an antioxidant and anti-inflammatory agent, KK-6 offers a promising avenue for alleviating inflammation-related damage and oxidative stress. This study lays the foundation for further exploration of giant salamander products and highlights their importance in health and novel food development. © 2024 Society of Chemical Industry.
研究领域:
生物化学
·
免疫学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2021
·
IF 3.228
Jianqing Chen,Bing Shao,Jinliang Wang,Zhiqiang Shen,Honggui Liu,Shu Li
Chlorpyrifos (CPF) is an organophosphate insecticide and can cause cell death of animals. In the study, the common carp were exposed to CPF at 0 μg/L (the control group), 1.16 μg/L (the low dose group), 11.6 μg/L (the medium dose group), and 116 μg/L (the high dose group), respectively. The carp were euthanized at the 30th day and gills were collected immediately. The ultrastructural and histopathological observations showed obvious necrosis characteristics and inflammatory injury in the CPF-treated groups. CPF exposure activated the MAPK pathway, in which the mRNA and protein expressions of extracellular signal-regulated (ERK), p38 MAP kinase (p38), and c-Jun N-terminal kinase (JNK) were increased; the mRNAs and proteins of NF-κB and TNF-α were activated; and the mRNAs and proteins of necroptosis related genes were changed (the mRNA and protein expression of RIPK1 , RIPK3 , MLKL, and FADD were increased and caspase-8 was decreased) with concentration dependency. Taken together, we concluded that CPF exposure activated the MAPK/NF-κB/TNF-α pathway, promoted inflammatory injure and evoked necroptosis in common carp gills. In addition, CPF-induced inflammation and necroptosis was concentration dependency. The toxic effects of CPF on gills provided data for both aquaculture and toxicological studies.
研究领域:
环境毒理学
·
鱼类生理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
·
2021
·
IF 3.636
Ling Zhang,Li-na Yao,Wei Liu,An-qi Chen,Shi-min He,Mei-li Wei,Zi-xuan Fan,Da-long Ren
N-acetylcholine receptors (AChRs) are mainly distributed in the postsynaptic membrane and have been widely studied for their control of muscle contraction by regulating neural action potentials. However, the influences of AChRs on immune responses and potential mechanisms remain unclear. Here, we used the advantages of live imaging of zebrafish to explore the regulation process of AChRs on inflammatory responses. Pharmacologically activating of the receptor, we found that the expression of pro-inflammatory cytokines il-1β, il-6, tnf-α and il-8 was significantly up-regulated and neutrophil migration to injury sites was also significantly increased. However, these phenomena were reversed under antagonism of the receptor activity. Results showed that interfering with nAChRs functions did not significantly affect zebrafish motion behavior. Results also showed that activation and antagonism of nAChRs function could regulate the phosphorylation of ERK protein respectively. We further demonstrated that ERK participated in the regulation of AChRs in cytokines expression and neutrophils migration in zebrafish. This study preliminarily revealed the roles of AChRs in inflammatory processes and their potential mechanism, providing additional evidence of peripheral immune regulation by cholinergic receptors.
研究领域:
免疫学
·
神经科学
·
斑马鱼生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
·
2025
·
IF 1.7
Xiaoyan Ding,Jinxi Wang,Xiangning Huang,Juan Huang
Diabetic cardiomyopathy (DCM), a life-threatening cardiovascular complication of diabetes, manifested as progressive cardiac dysfunction mediated through oxidative stress, inflammation, and apoptosis. Loganic acid (LA), a natural iridoid compound with anti-inflammatory and antioxidant properties, has demonstrated therapeutic potential in various inflammatory disorders, but its role in DCM remains unexplored. Here, we systematically investigated LA’s cardioprotective potential and its mechanisms. Utilizing a high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mouse model, LA (30 mg/kg, oral gavage) was administered for 8 weeks post-diabetes confirmation. Echocardiographic assay indicated that LA improved cardiac function. Histopathologic evaluation displayed that LA attenuated myocardial structural disorders, reduced collagen deposition, and suppressed cardiomyocyte apoptosis. Furthermore, LA treatment normalized redox imbalance (decreased MDA and increased GSH) and reduced inflammatory cytokine levels. In vitro , a diabetic cell model was established with AC16 cardiomyocytes exposed to high glucose (HG; 30 mM). The findings demonstrated that LA (25 or 50 μM) dose-dependently ameliorated HG-induced cardiomyocyte damage, oxidative stress, and inflammatory cytokine release. Mechanistically, LA treatment suppressed HG-induced activation of TLR4 signaling and phosphorylation of p38 MAPK. Collectively, these findings highlight LA as a novel therapeutic candidate in DCM, targeting the TLR4/p38 MAPK axis to attenuate diabetes-induced cardiac damage.
研究领域:
心血管病学
·
糖尿病学
·
分子药理学
·
氧化应激
·
炎症生物学
·
信号转导
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2021
·
IF 5.34
Zi-ling Zou,Ming-hui Sun,Wei-feng Yin,Lei Yang,Ling-yi Kong
Background Osteoarthritis (OA) is an intractable degenerative disease of the whole joint, which is characterized by synovitis inflammation, cartilage damage, and chronic pain. Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) performs an important role in OA. Purpose We aim to investigate avicularin to protect cartilage extracellular matrix degradation (ECM) and suppresses inflammation both in rat and human chondrocytes . Methods 5-Ethynyl-2′-deoxyuridine (EdU) staining, Quantitative real-time PCR, TRAF6 plasmid transfection, Western blot , Measurement of nitric oxide (NO), ROS detection and Immunofluorescence were utilized in vitro . micro-CT scanning, Safranin O-Fast Green, toluidine blue and immunohistochemistry staining were performed in vivo . Results In vitro , avicularin attenuates the degradation of ECM and inflammation, which could inhibit the activation of TRAF6/MAPK pathway via targeting TRAF6. Increased MMP3 and MMP13 expressions and decreased Aggrecan and Collagen Ⅱ levels were observed in anterior cruciate ligament transection (ACLT) induced osteoarthritic rats. Interestingly, intra-articular injection of avicularin attenuates this phenomenon. Conclusions Taken together, our results indicate that avicularin suppresses cartilage extracellular matrix degradation and inflammation via TRAF6/MAPK activation by targeting TRAF6. These observations identify TRAF6 as a relevant drug target, and avicularin may as a potential therapeutic agent in osteoarthritis.
研究领域:
药理学
·
风湿病学
·
骨科
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PeerJ
·
2025
·
IF 2.4
Jia Song,Jinyu Qiao,Mingxue Chen,Jiahui Li,Jixia Wang,Dayong Yu,Huachuan Zheng,Liying Shi
Chaetoglobosin A (ChA) is an antitumor compound produced by Chaetomium globosum . However, the mechanism of its antitumor effect has been rarely reported. In this study, we evaluated the anti-proliferative effect of ChA on T-24 human bladder cancer cells and explored its mechanism of action. ChA was found to have a good inhibitory effect on T-24 cells by MTT assay with an IC50 value of 48.14 ± 10.25 μΜ. Moreover, it was found to have a migration inhibitory ability and a sustained proliferation inhibitory effect on tumor cells by cell aggregation assay and cell migration assay. The cells morphological changes were determined by Hoechst33342 assay. While Annexin V-FITC/PI double-staining assay also demonstrated that the number of apoptotic cells increased with the increase of drug concentration. Flow cytometry results showed that ChA treatment increased reactive oxygen species (ROS) and decreased mitochondrial membrane potential (MMP) in T-24 cells and inhibited cell mitosis, resulting in an increase in the number of sub-G1 phase cells. Further western blot experiments demonstrated that MAPK and PI3K-AKT-mTOR pathways were activated after drug treatment in addition to endogenous and exogenous apoptotic pathways. The addition of the ROS inhibitor N-acetylcysteine (NAC) upregulated the expression level of Bcl-2 protein, decreased p38 phosphorylation, increased ERK phosphorylation and restored the levels of PI3K and p-mTOR after ChA treatment. These suggest that ChA induces apoptosis by regulating oxidative stress, MAPK, and PI3K-AKT-mTOR signaling pathways in T-24 cells.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL NEUROLOGY
·
2023
·
IF 5.3
Jing Zhao,Meini Le,Jie Li,Qiong Huang,Haocong Chen,Wenyi Zhang,Huiwen Mao,Qing Sun,Aiguo Li,Yingmin Zhao,Lingling Yu,Mingjiang Yi,Jie Wang,Xinyuan Li,Guangming Zhang,Jun Ma,Xiaohua Dong
Hypoxic-ischemic encephalopathy (HIE) is an important factor leading to permanent damage of central nervous system (CNS) and even neonatal death . Long non-coding RNAs (lncRNAs) has been shown to get involved in the pathogenesis of nervous system diseases . LINC00938 is an intergenic lncRNA which is reported to be involved in neurodegenerative disease . However, the potential role of LINC00938 in nerve injury of neonatal HIE is undetermined. Here, we found that the expression of LINC00938 in the whole blood of neonates with HIE was downregulated compared with the non-HIE group. Functional study revealed that the expression of LINC00938 was significantly decreased in oxygen-glucose deprivation (OGD)-induced SH-SY5Y. Knockdown of LINC00938 induced the neural cell apoptosis by increased the protein level of Bax, Cleaved-Caspase3 and decreased the expression of Bcl-2. In addition, overexpression of LINC00938 prevented the apoptosis of SH-SY5Y from OGD injury. RNA-seq analysis showed that MAPK signaling was involved in the anti-apoptosis function of LINC00938. LINC00938 knockdown induced the activation of c-Jun-N-terminal kinase (JNK), p38 mitogen-activated protein kinase, and inhibited the activation of ERK signaling. However, LINC00938 play neuroprotective role in OGD-induced SH-SY5Y by suppression the phosphorylation of JNK and p38 MAPK rather than regulation of ERK signaling pathway . Further analyses illustrated that the cell apoptosis of neuronal cell was dependent on the elevation of reactive oxygen species (ROS) and result in mitochondria dysfunction in LINC00938 knockdown SH-SY5Y. Pretreated with ROS inhibitor N -acetylcysteine amide (NACA) dramatically suppressed LINC00938 knockdown induced oxidative stress and mitochondria dysfunction which induced cell apoptosis. In addition, NACA treatment significantly reduced the expression of p-JNK and p-p38 in OGD-induced SH-SY5Y. Furthermore, overexpression of LINC00938 displayed a notably neuroprotective effect by suppress central nervous system cell apoptosis via alleviating oxidative stress in CoCl 2 -induced hypoxic HIE model of zebrafish. Taken together, these results suggested that LINC00938 can act as a neuroprotective factor to inhibit oxidative stress and apoptosis of CNS under HIE conditions.
研究领域:
神经科学
·
分子生物学
·
儿科
·
细胞生物学
✓ 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）