PLoS One
·
2024
·Vol. 19
·期 3
·e0301133
·
IF 2.9
Suye Ran,Lingyu Song,Hong Yang,Jiangnan Yu,Yunhuan Zhen,Qi Liu
Purpose
Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD), which has a high risk of cirrhosis, liver failure, and hepatocellular carcinoma. Piperine (Pip) is an extract of plants with powerful anti-inflammatory effects, however, the function of Pip in NASH remains elusive. Here, we aim to explore the role of Pip in NASH and to find the possible mechanisms.
Methods
Methionine and choline-deficient (MCD) diets were used to induce steatohepatitis, methionine- and choline-sufficient (MCS) diets were used as the control. After Pip treatment, H&E staining, Oil Red O staining, hepatic triglyceride (TG) content and F4/80 expression were performed to analysis liver steatosis and inflammation; Masson’s staining, COL1A1 and α-SMA were detected liver fibrosis. Lipopolysaccharide (LPS) -treated AML12 cells were used to as the cell model to induce pyroptosis. Then, pyroptosis-related proteins, IL-1β and LDH release were detected in vivo and in vitro . Finally, NF-κB inhibitor, BAY11-7082, was used to further demonstrate the mechanism of Pip in NASH.
Results
The study found that Pip alleviated liver steatosis, inflammation, hepatocyte injury, and fibrosis in mice fed with MCD diets. Moreover, the pyroptosis markers (NLRP3, ASC, caspase-1 p20, and GSDMD), IL-1β and LDH release were decreased by Pip treatment. NF-κB activation was suppressed by Pip treatment and pyroptosis-related proteins were down regulated by BAY11-7082.
Conclusion
Pip ameliorates NASH progression, and the therapeutical effect was associated with inhibition of hepatocyte pyroptosis induced by NF-κB.
研究领域:
药理学
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肝病学
·
免疫学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
iScience
·
2024
·
IF 4.6
Ruobing Wang,Dan Su,Yueze Liu,Hua Huang,Jiangdong Qiu,Zhe Cao,Gang Yang,Hao Chen,Wenhao Luo,Jinxin Tao,Guihu Weng,Taiping Zhang
Summary Nuclear factor kappa B (NF-κB) plays a pivotal role in the development of pancreatic cancer, and its phosphorylation has previously been linked to the regulation of NUAK2. However, the regulatory connection between NF-κB and NUAK2, as well as NUAK2’s role in pancreatic cancer, remains unclear. In this study, we observed that inhibiting NUAK2 impeded the proliferation, migration, and invasion of pancreatic cancer cells while triggering apoptosis. NUAK2 overexpression partially resisted apoptosis and reversed the inhibitory effects of the NF-κB inhibitor. NF-κB transcriptionally regulated NUAK2 transcription by binding to the promoter region of NUAK2. Mechanistically, NUAK2 knockdown remarkably reduced the expression levels of p -SMAD2/3 and SMAD2/3, resulting in decreased nuclear translocation of SMAD4. In SMAD4-negative cells, NUAK2 knockdown impacted FAK signaling by downregulating SMAD2/3. Moreover, NUAK2 knockdown heightened the sensitivity of pancreatic cancer cells to gemcitabine, suggesting that NUAK2 inhibitors could be a promising strategy for pancreatic cancer treatment.
研究领域:
肿瘤学
·
分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Liming Hou,Xiaoming Wang,Min Bai,Qian Li,Wei Zhang,Hui Su,Yan Liu
Myocardial ischemia–reperfusion (MI/R) injury represents a significant complication associated with reperfusion therapy for myocardial infarction. Leucine-rich repeat-containing protein 8A (LRRC8A), a volume-regulated anion channel protein, involved in cellular homeostasis, has been implicated in the progression of cardiovascular events, but its role in MI/R remains uninvestigated. Here, we sought to characterize the role of LRRC8A in MI/R injury and uncover its potential mechanism. A rat MI/R model was developed via left anterior descending coronary artery ligation for 45 min followed by 4 h reperfusion to assess changes in LRRC8A expression in the myocardium. The results revealed that LRRC8A was upregulated in rat hearts after MI/R injury. To silence LRRC8A expression, we injected adenovirus encoding LRRC8A shRNA into the myocardium of MI/R rats 3 days before ischemic surgery. We observed that LRRC8A silencing in post-MI/R rats reduced myocardial infarct area, suppressed cardiomyocyte apoptosis and enhanced cardiac function. Furthermore, rat H9c2 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate MI/R injury in vivo , and the findings indicated that LRRC8A silencing reduced OGD/R-induced cardiomyocyte apoptosis, while its upregulation had an opposite effect, as Bcl-2 expression, Tunel staining demonstrated. Mechanistically, LRRC8A can interact with tripartite motif containing 21 (TRIM21) and subsequently suppress the focal adhesion kinase (FAK)/NF-κB pathway, thereby facilitating cardiomyocyte apoptosis. TRIM21 knockdown eliminated the pro-apoptotic effect of LRRC8A and decreased the inhibitory effect of LRRC8A on the FAK/NF-κB pathway in MI/R rats as well as in OGD/R-exposed cardiomyocytes.
研究领域:
心血管疾病
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2025
·
IF 4.9
Changtong Guo,Xiangda Shi,Bingbing Luo,Yuxuan Yang,Jian Huang,Jiale Xu,Rong Zheng,Siwen Jiang,Jin Chai
In actual production, the restraint stress caused by crowded and narrow spaces, as well as operations such as capture and transportation, can lead to intestinal inflammation and affect animal growth performance, damaging the economic benefits of livestock farms. Isovaleric acid, a type of short-chain fatty acid (SCFA), has been found to be useful in enhancing calf digestion and inhibiting the expression of inflammatory factors. In this study, we first constructed a mouse model of chronic restraint stress (CRS) and fed a diet supplemented with sodium isovalerate to mice with CRS to investigate the mitigating effect of exogenously added isovalerate on mice with chronic restraint stress. An inflammation model was then constructed using piglet jejunal epithelial cell line-J2 (IPEC-J2) to simulate intestinal inflammation after stress, and to investigate the mitigating effect of isovaleric acid on inflammation as well as the repairing effect on intestinal barrier. The results showed that feeding sodium isovalerate significantly increased the weight gain as well as the body weight growth rate of CRS mice from 1-28 days ( P < 0.05), and extremely significantly decreased the feed intake and feed to gain ratio of CRS mice ( P < 0.01). In addition, feeding sodium isovalerate ameliorated the decrease in organ index in mice caused by CRS and significantly increased leg muscle index in CRS mice ( P < 0.05). Meanwhile, feeding sodium isovalerate improved depressive behavior and promoted 5-HT secretion in the brain and hypothalamus of CRS mice. Besides, feeding sodium isovalerate ameliorated intestinal inflammation in CRS mice, as evidenced by extremely significantly decreased the expression of colonic inflammatory factors and increased the expression of tight junction proteins ( P < 0.01). It was found that the addition of isovaleric acid extremely significantly reduced the expression of inflammatory factors and the phosphorylation level of NF-κB p65 in inflammatory cells ( P < 0.01), extremely significantly increased the survival rate of inflammatory cells ( P < 0.01) and the expression of tight junction proteins ( P < 0.05), improved the morphology of inflammatory cells. After the addition of short-chain fatty acid receptor GPR41 and GPR43 antagonists, the resistance effect of isovaleric acid on inflammation was inhibited. The above results suggest that isovaleric acid has an ameliorating effect on CRS in mice and inhibits NF-κB activation thereby exerting its anti-inflammatory effect.
研究领域:
生物化学
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免疫学
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动物营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2020
·
IF 2.205
Aimin Liu,Buxin Zhang,Wei Zhao,Yuanhui Tu,Qingxing Wang,Jing Li
Psoriasis is a chronic inflammatory skin disease that affects approximately 2% of worldwide population, and causing long-term troubles to the patients. Therefore, it is urgent to develop safe and effective therapeutic drugs. Catalpol is a natural iridoid glucoside, that has several remarkable pharmacological effects, however, whether catalpol can alleviated psoriasis has not been explored. The goal of the present work is to study the role of catalpol in psoriasis in vivo and in vitro. Imiquimod-induced psoriasis-like mice were applied with different concentrations of catalpol for 8 consecutive days. The severity degree of psoriasis was estimated and the skin pathological changes were detected by H&E staining. Also, TNF-α-stimulated keratinocytes were treated with different concentrations of catalpol, then the oxidative stress and inflammation factors, as well as the expression of SIRT1 and activation of NF-kB and MAPK pathways were measured. The results showed that catalpol reduced the erythema, scaling, ear thickness, and changed pathological phenotypes in the lesioned skin region in mice. Treatment with catalpol significantly suppressed the oxidative stress and inflammatory reactions in vivo and in vitro, as reflected by the decreased secretion or expression of oxidative stress indicators and proinflammatory factors. Furthermore, the SIRT1 was up-regulated and the NF-κB and MAPKs signaling pathways were suppressed by the treatment of catalpol in vivo and in vitro. In summary, our data suggested that catalpol may have a therapeutic property of psoriasis by ameliorating oxidative stress and inflammation partly through SIRT1 mediated suppression of NF-κB and MAPKs pathways.Abbreviation: CAT: catalase; ELISA: enzyme-linked immunosorbent assay; GSH: glutathione; HRP: horseradish peroxidase; IMQ: imiquimod; JNK: c-Jun NH 2-terminal kinases; MAPKs: mitogen-activated protein kinases; MDA: malondialdehyde; NC: negative control group; NF-kB: nuclear factor kappa B; PASI: psoriasis area and severity index; PVDF: polyvinylidene difluoride membranes; qRT-PCR: quantitative real time polymerase chain reaction; ROS: reactive oxygen species; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel; SIRT1: silent information regulator 1; SOD: Cu/Zn superoxide dismutase
研究领域:
药理学
·
皮肤科
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Bin Hu,Gongwen Du
Osteoarthritis (OA) is an age-related joint disease characterized by progressive heterogeneous changes in articular cartilage and subchondral bone. Osteoclast stimulating factor 1 (OSTF1) is a small intracellular protein involved in bone formation and bone resorption. However, to our best knowledge, its role in OA is still unclear. In this study, an OA rat model was established by anterior cruciate ligament transection (ALCT). OSTF1 was increased in the cartilage tissues of OA patients and OA rats. Next, the role of OSTF1 in interleukin-1β (IL-1β)-induced chondrocyte apoptosis, inflammation and extracellular matrix degradation was explored through loss of function assays. Strikingly, OSTF1 knockdown relieved IL-1β-induced chondrocyte apoptosis, with decreased cleaved caspase-3 and cleaved PARP levels. Besides, OSTF1 knockdown restrained IL-1β-induced inflammation and degradation of extracellular matrix of chondrocytes. Subsequently, the molecular mechanism of OSTF1 was explored. Transcriptomic analysis revealed the potential gene network map regulated by OSTF1 knockdown. Some differentially expressed genes (DEGs) were involved in regulating the NF-κB signaling pathway. Furthermore, our results demonstrated that OSTF1 knockdown inhibited IL-1β-activated the NF-κB signaling pathway. Ultimately, we analyzed the potential gene network map regulated by OSTF1 and its downstream NF-κB. Bioinformatics analysis showed that 18 DEGs in OSTF1-silenced chondrocytes overlapped with the NF-κB downstream targets. Collectively, our findings indicate that OSTF1 knockdown mitigates IL-1β-induced chondrocyte injury via inhibiting the NF-κB signaling pathway.
研究领域:
医学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
·
2025
·
IF 3.8
Jiajia Chen,Huanle Liu,Yanfang Fu,Xiaolan Chen,Shiqin Zhang,Yongqi Yang,Shengwen Li,Guixiang Wang,Tian Lan
Background Chronic liver inflammation is a major cause of death in patients with liver fibrosis and cirrhosis, which pose a serious health threat worldwide, and there is no effective anti-hepatic fibrosis drug. Kaempferol (KA), a flavonoid polyphenol extracted from many edible plants and traditional Chinese medicine, has been reported to possess anti-inflammatory, antioxidant, and antitumor activities and has an ameliorating effect on liver fibrosis or other fibroproliferative diseases. However, the specific regulatory mechanism of KA-reversed macrophage M1 polarization is still obscure. This study aimed to investigate the protective effects of KA on carbon tetrachloride (CCl 4 )-induced liver fibrosis in mice through M1 polarization. Methods C57BL/6 mice were intraperitoneally injected with CCl 4 twice weekly to induce liver fibrosis. Male mice were randomly divided into four groups (n = 5): the oil group, the CCl 4 group, the low-dose KA-treatment CCl 4 group (50 mg/kg/d KA), and the high-dose KA-treatment CCl 4 group (100 mg/kg/d KA). An equal amount of solvent was given to each group by intraperitoneal injection. Results The results indicated that KA decreased liver pathologic changes, hepatic macrophage recruitment, and serum alanine aminotransferase (ALT) levels. Notably, it reduced the activation of M1-type macrophages in the liver. The expression of proinflammatory cytokines and genes associated with M1 macrophages, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1β, and inducible nitric oxide synthase (iNOS), was also decreased. The core targets, signaling pathways, and possible mechanisms related to the M1 polarization of KA were analyzed by network pharmacology and molecular docking. Further analysis revealed that KA regulated MAPK/NF-κB signaling pathways. Finally, the results indicated that KA regulates M1 macrophage activation by modulating the MAPK/NF-κB signaling pathways. Conclusions This study revealed that KA ameliorated liver injury, inflammation, and fibrosis by inhibiting macrophage M1 polarization through the MAPK/NF-ҡB signaling pathway, highlighting KA as a potential novel agent for the prevention and treatment of liver fibrosis.
研究领域:
药理学
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肝脏病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDIATORS OF INFLAMMATION
·
2018
·
IF 3.549
Yiyi Jin,Jianchang Qian,Xin Ju,Xiaodong Bao,Li Li,Suqing Zheng,Xiong Chen,Zhongxiang Xiao,Xuemei Chen,Weiwei Zhu,Weixin Li,Wencan Wu,Guang Liang
Inflammation is a key factor in the pathogenesis of ALI. Therefore, suppression of inflammatory response could be a potential strategy to treat LPS-induced lung injury. Osthole, a natural coumarin extract, has been reported to protect against acute kidney injury through an anti-inflammatory mechanism, but its effect on ALI is poorly understood. In this study, we investigated whether osthole ameliorates inflammatory sepsis-related ALI. Results from in vitro studies indicated that osthole treatment inhibited the LPS-induced inflammatory response in mouse peritoneal macrophages through blocking the nuclear translocation of NF-κB. Consistently, the in vivo studies indicated that osthole significantly prolonged the survival of septic mice which was accompanied by inflammation suppression. In the ALI mouse model, osthole effectively inhibited the development of lung tissue injury, leukocytic recruitment, and cytokine productions, which was associated with inhibition of NF-κB nuclear translocation. These findings provide evidence that osthole was a potent inhibitor of NF-κB and inflammatory injury and suggest that it could be a promising anti-inflammatory agent for therapy of septic shock and acute lung injury.
研究领域:
药理学
·
免疫学
·
病理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROTOXICOLOGY AND TERATOLOGY
·
2025
·
IF 2.8
Fangfei Li,Jie Zhang,Xiaoli Ma,Hao Chen,Guiqiang Liang,Yunfeng Zou
Excessive accumulation of manganese (Mn) can cause neuroinflammation, impairing cognitive function. SPON1, a secreted glycoprotein in the extracellular matrix, is implicated in neuroinflammation, but its role in activating pro-inflammatory pathways in Mn-induced neuroinflammation remains unclear. This study employed in vivo and in vitro models to investigate Mn neuroinflammation. The expression levels of SPON1 and the ERK1/2/NF-κB pathway associated with inflammation were measured in male C57BL/6 mice after gavage of Mn at different doses (0, 25, 50, 100 mg/kg) for 12 weeks. SPON1 levels were measured after primary hippocampal neurons, primary cortical neurons, neuroblastoma cells (N2a), and microglial cells (BV2) were exposed to various concentrations of Mn for 24 h. We observed that in vivo Mn exposure significantly decreased SPON1 expression in the cortex but not in the hippocampus. Similarly, in vitro experiments demonstrated that Mn exposure significantly reduced SPON1 levels in primary cortical neurons, N2a, and BV2. In addition, Mn exposure increased the expression levels of ERK1/2 and NF-κB pathway proteins in the mouse cortex. Because BV2 cells are susceptible to inflammatory signals, they were chosen to elucidate how SPON1 induces neuroinflammation during Mn exposure. SPON1 knockdown increases the expression of inflammatory factors, whereas SPON1 overexpression inhibits the activation of the ERK1/2/NF-κB pathway and reduces inflammatory factor levels. In summary, these results suggest that Mn may affect the activation of ERK1/2/NF-κB pathway and the expression of inflammatory factors by inhibiting SPON1, ultimately promoting neuroinflammation.
研究领域:
神经科学
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毒理学
·
分子生物学
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免疫学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
GENOMICS
·
2023
·
IF 4.4
Dan Chen,Li Shi,Dingfu Zhong,Ying Nie,Yi Yang,Dong Liu
Background Gastric cancer (GC) is a common cancer with a high incidence and mortality rate. Herein, the role of hsa_circ_0002019 (circ_0002019) in GC was investigated. Methods The molecular structure and stability of circ_0002019 were identified by RNase R, and Actinomycin D treatment. Molecular associations were verified by RIP. Proliferation, migration, and invasion were detected by CCK-8, EdU, and Transwell, respectively. The effect of circ_0002019 on tumor growth was analyzed in vivo. Results Circ_0002019 was elevated in GC tissues and cells. Circ_0002019 knockdown inhibited the proliferation, migration, and invasion. Mechanically, circ_0002019 activated NF-κB signaling by increasing TNFAIP6 mRNA stability by PTBP1. Activation of NF-κB signaling limited the antitumor effect of circ_0002019 silencing in GC. Circ_0002019 knockdown inhibited tumor growth in vivo by reducing TNFAIP6 expression. Conclusions Circ_0002019 accelerated the proliferation, migration, and invasion by regulating TNFAIP6/NF-κB pathway, suggesting circ_0002019 could be a key regulatory factor in GC progression.
研究领域:
肿瘤学
·
分子生物学
·
癌症遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Frontiers
·
2025
·
IF 6.9
Xiaoli Qin,Yan Lu,Yawen Luo,Yafang Cui,Kai Zhao,Yang He,Muhammad Aziz ur Rahman,Shengnan Min,Wenfang Wang,Fuyu Yang,Binghai Cao,Huawei Su
Alfalfa is rich in flavonoid compounds, which are known for their antioxidative and anti-inflammatory properties, suggesting therapeutic potential for alfalfa flavonoids (AF) in inflammation-related diseases. This study investigated the effects of AF on Salmonella -induced colitis, a severe inflammatory bowel disorder characterized by oxidative damage and inflammatory response. In vitro, antioxidant assays revealed AF's concentration-dependent radical scavenging, significantly reducing electron paramagnetic resonance (EPR) signals for HO • and O 2 •− by 42% and 54%, respectively. In vivo, AF treatment significantly mitigated body weight (BW) loss by 6%, increased colon length by 11%, and reduced liver and spleen weights by 19% and 81%, respectively, compared to the colitis group. Mechanistically, AF suppressed inflammation by downregulating the Toll-like receptor 4 (TLR4)/IκB/nuclear factor-κB (NF-κB)/cyclooxygenase-2 (COX-2) pathway and inhibiting nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby lowering levels of pro-inflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6], interleukin 1 beta [IL-1β]). Concurrently, AF enhanced antioxidant defense via the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels while increasing catalase (CAT) (69%), glutathione peroxidase (GPx) (83%), and superoxide dismutase (SOD) (21%) activities. Moreover, AF preserved epithelial and mucosal barriers by reducing apoptosis and upregulating tight junction proteins (Claudin1, ZO-1, E-cadherin) and goblet cell marker Ulex europaeus (Gorse) Agglutinin I (UEA-1). Microbiota analysis revealed that AF significantly enriched beneficial bacteria, including Akkermansia , Oscillibacter , and butyrate-producing taxa, thereby counteracting Salmonella -induced dysbiosis. Furthermore, AF restored the disrupted profile of short-chain fatty acids (SCFAs), strengthening the relationship between symbiotic microbiota and mucosal defense. Overall, AF exerted multifaced protection against Salmonella -induced colitis by alleviating oxidative stress, stabilizing intestinal homeostasis, and thus attenuating inflammation. These findings make AF a promising phytopharmaceutical for the prevention and treatment of inflammatory diseases.
研究领域:
药理学
·
微生物学
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免疫学
✓ 已验证
产品关联
DOI
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2025
·
IF 3.9
Mijia Li,Wei Yuan,Shiyi Duan,Yang Li,Sijie Zhang,Yan Zhao,Shimei Xiao,Keyuan Zhong
The large-scale mining and utilization of rare earth elements have significantly increased their concentration in the environment, especially in regions surrounding mining areas. These environmentally-enriched rare earth elements accumulate in agricultural products and organisms through soil and water, potentially impacting in human health through the food chain. Erbium (Er), a rare earth element of the lanthanide series (Group IIIB), plays a crucial role in various modern technological applications. It is primarily utilized in ceramics, glass coloring, optical fibers, laser technology, and the nuclear industry, among others. However, a paucity of information on the health effects and ecotoxicity of erbium is currently available. In this study, we used the zebrafish as experimental animal to investigate the potential impact of the rare earth element erbium on the immune system. We exposed fertilized zebrafish embryos to different concentrations of erbium (0, 4, 8 and 16 mg/L) from 6 hours post-fertilization (hpf) until 72 hpf. We found that with increasing concentrations of erbium exposure, there was an increasing and dispersing trend in the number of zebrafish neutrophils; a decreasing trend in the number of macrophages. Exposure to erbium was demonstrated to impair the phagocytic capability of macrophages, reduce the recruitment of neutrophils to the wound site, and lower the resistance of zebrafish to Escherichia coli infection. Erbium exposure led to macrophage apoptosis and upregulation of oxidative stress in the zebrafish. The individual application of the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine, the IKBKB inhibitor resveratrol and the NF-κB inhibitor andrographolide was demonstrated to alleviate erbium-induced immune toxicity, as confirmed by assays including acridine orange staining, neutrophil enumeration and recruitment, and real-time quantitative PCR. Therefore, the rare earth element erbium induced immune toxicity in zebrafish through the ROS/NF-κB pathway. The findings of this study provide information for assessing the impact of rare earth elements on human health and ecosystems.
研究领域:
环境毒理学
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免疫学
·
分子生物学
✓ 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）