查找使用阿拉丁产品的科研文献

Long noncoding RNA BMPR1B-AS1 facilitates endometrial cancer cell proliferation and metastasis by sponging miR-7-2-3p to modulate the DCLK1/Akt/NF-κB pathway

Tianjiao Lai,Haifeng Qiu,Lulu Si,Yu Zhen,Danxia Chu,Ruixia Guo

Endometrial carcinoma (EC) originates from the endometrium and is one of the most common tumors in female patients, and its incidence has continued to increase in recent decades. LncRNAs are involved in the pathogenesis and metastasis of a variety of malignant tumors, which indicates that lncRNAs can be used as tumor diagnostic markers and potential therapeutic targets. In this study, we analyzed the RNA transcripts of EC cells from The Cancer Genome Atlas (TCGA) and first reported a novel lncRNA, BMPR1B-AS1, that was more highly expressed in endometrial cancer tissues than in adjacent tissues, and BMPR1B-AS1 could promote endometrial cancer cell proliferation and metastasis. Bioinformatics prediction and experimental results both suggested that BMPR1B-AS1 could modulate the malignant behaviors of endometrial cancer cell lines by sponging miR-7-2-3p to modulate DCLK1, and a DCLK1 inhibitor blocked the activation of the PI3K/Akt/NF-κB signaling pathway. Collectively, this study suggests that the BMPR1B-AS1/miR-7-2-3p/DCLK1 axis contributes to the proliferation and metastasis of endometrial cancer cells via the PI3K/Akt/NF-κB pathway.

Guanxinping Tablets Inhibit ET-1-Induced Proliferation and Migration of MOVAS by Suppressing Activated PI3K/Akt/NF-κB Signaling Cascade

Ying-Ying Wu,Yi-Lin Huang,Bin Dai,Jian-Wei Liu,Xu Han

Background/Aim. Abnormal proliferation and migration of vascular smooth muscle cells is one of the main causes of atherosclerosis (AS). Therefore, the suppression of abnormal proliferation and migration of smooth muscle cells are the important means for the prevention and inhibition of AS. The clinical effects of Guanxinping (GXP) tablets and preliminary clinical research on the topic have proved that GXP can effectively treat coronary heart disease, but its underlying mechanism remains unclear. This study aimed to confirm the inhibitory effect of GXP on the abnormal proliferation of mouse aortic vascular smooth muscle (MOVAS) cells and to explore the underlying mechanism. Methods. MOVAS cells were divided into two major groups: physiological and pathological groups. In the physiological group, MOVAS cells were directly stimulated with GXP, whereas in the pathological group, the cells were stimulated by endothelin-1 (ET-1) before intervention by GXP. At the same time, atorvastatin calcium, which effectively inhibits the abnormal proliferation of MOVAS cells, was used in the negative control group. CCK8 assay, scratch test, ELISA, Western blotting, and immunofluorescence staining were performed to observe the proliferation and migration of MOVAS cells and the expression levels of related factors after drug intervention in each group. Results. In the physiological group, GXP had no significant effect on the proliferation and migration of MOVAS cells and the related factors. In the pathological group, a high dose of GXP reduced the abnormal proliferation and migration of MOVAS cells. Further, it reduced the expression levels of PI3K; inhibited the phosphorylation of Akt (protein kinase B); upregulated IκB-α levels; prevented nuclear factor kappa B (NF-κB) from entering the nucleus; downregulated the expression of interleukin 6 (IL6), IL-1β, and iNOS; and upregulated the ratio of apoptosis-related factor Bax/Bcl-2. There was no significant difference between the high-dose GXP group and the atorvastatin calcium group (negative control group). Conclusion. Our findings revealed that GXP was able to inhibit the proliferation and migration of MOVAS cells by regulating the PI3K/Akt/NF-κB pathway.

Pyrazole permethrin-induced liver toxicity in mice involves the PI3K/AKT/NF-κB pathway: Integrated network pharmacology and experimental validation

Jingjing Chen,Bin Liu,Yuanyuan Li,Binwu Zhuang,Dong Su,Yunlong Sang,Zibo Dong,Hao Liu

Pyrazole permethrin (also known as pyraclostrobin, abbreviated as PP) is a widely used fungicide that is chemically stable and fat-soluble; however, due to its accumulation in the environment and bioaccumulation, it poses potential health risks.This study systematically elucidates PP-induced liver injury through a combination of network toxicology and in vitro/in vivo investigations. Network toxicology identified 328 potential targets and 12 core genes associated with PP-induced liver injury. GO and KEGG enrichment analyses revealed pathway enrichment emphasizing biological processes such as inflammation, oxidative stress, apoptosis, and lipid metabolism. In vivo experiments in mice revealed that after 28 days of exposure, histopathological analysis showed minor local inflammatory cell infiltration and extensive hepatocyte necrosis and vacuolation in both low- and high-dose groups. High-dose PP significantly elevated serum transaminase (AST and ALT) activity. Biochemical analysis revealed that PP treatment reduced antioxidant enzyme activity (CAT, T-AOC, GSH-Px) while increasing malondialdehyde (MDA) levels, inducing oxidative stress. Additionally, PP exposure enhanced the expression of inflammatory cytokines (IL-1β, TNF-α). This indicates activation of oxidative stress and inflammatory pathways: oxidative damage occurs via depletion of the antioxidant enzyme system, while inflammatory cascades are mediated through the PI3K/AKT/NF-κB signaling axis. This study reveals key molecular targets and pathways involved in PP-induced hepatotoxicity, suggesting that subacute exposure risks should be fully considered when establishing safety standards for agricultural chemical use.

Shi-Wei-Long-Dan-Hua capsule alleviates LPS-induced acute lung injury by suppressing pulmonary inflammation and the PI3K-Akt-NF-κB/MAPK axis

Qian Sun,Shi-Liu Xu,Shuang-Ning Liu,De-Jian Chen,Zheng-Jun Li,Xiao-Jun Qiu,Xia Yang,Feng-Xiang Zhang,Jian-Xin Chen

SWLDH was firstly confirmed to treat bacterial infection-induced ALI. • PI3K-AKT/NF- κ B and MAPK signaling pathways were confirmed as the core mechanism for SWLDH to treat ALI. • Five potential anti-ALI compounds in SWLDH were identified. Shi-Wei-Long-Dan-Hua capsule (SWLDH) is clinically used to alleviate bacterial or viral infection induced bronchitis. Recent studies have reported its effects on viral infection induced acute lung injury, broadening our understanding of its clinical applications. However, its effects against bacterial infection-induced ALI were still unclear, along with not fully elucidated chemical profile, significantly limiting its clinical application and product improvement. In this work, we aimed to systematically characterize the chemical components in SWLDH and explore its effects and mechanisms against bacterial infection-induced ALI. Results showed that SWLDH (2 g/kg/day) significantly reduced lung index, alleviated pathological injury and depressed cytokine expression in LPS-challenged mice. SWLDH also inhibited LPS-induced over-expression of iNOS and pro-inflammatory cytokines (TNF- α , IL-1 β , IL-6) in RAW264.7 cells. Moreover, 128 chemical components in SWLDH and its 32 prototypes in rats were identified by using UPLC-Q/TOF MS. Network pharmacology and Western blot were used to confirm that SWLDH can alleviate LPS- induced ALI by suppressing pulmonary inflammation and the PI3K-Akt-NF- κ B/MAPK axis. Further, five potential anti-ALI substances in SWLDH were found. This is the first time to comprehensively profile the chemical components in SWLDH and reveal its effects and mechanisms against bacterial infection-induced ALI, providing the potential substances and pharmacological data for further quality improvement and product development. Download: Download high-res image (166KB) Download: Download full-size image

Shen-Qi-Ling extract alleviates spleen deficiency syndrome in mice: insights into the gut microbiota–metabolite axis and PI3K/Akt/NF-κB/AQP3 signaling pathway

Xiao Qiang,Mengyuan Gao,Zongshuo Li,Weidong Li

SQLE is a potential functional food for alleviating spleen deficiency syndrome. • SQLE contains diverse bioactive compounds with flavonoids as major components. • SQLE restores gut microbiota homeostasis and promotes SCFAs production. • SQLE improves spleen deficiency via the PI3K/Akt/NF-κB/AQP3 signaling pathway. Spleen deficiency syndrome (SDS) manifests as impaired digestive function, fatigue, and metabolic issues, which are closely associated with dysbiosis of the gut microbiota. Shen-Qi-Ling extract (SQLE) is a natural extract prepared from food-medicine homologous resources, primarily consisting of Codonopsis pilosula , Astragalus membranaceus , and Poria cocos . However, the bioactive constituents and mechanisms by which it alleviates SDS remain unclear. In this study, we systematically characterized the chemical constituents of SQLE and elucidated its potential mechanisms of action against SDS in mice. Using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) analysis, 137 compounds were identified in SQLE, with flavonoids being the most abundant, followed by coumarins, phenylpropanoids, and organic acids. Molecular docking analysis indicated that SQLE might have a spleen-strengthening effect. Treatment with SQLE, particularly SQLE-M, significantly enhanced intestinal absorption, exercise performance, tissue damage, and oxidative stress. Moreover, SQLE-M restored gut microbial homeostasis, increased the relative abundance of potentially beneficial bacteria, and promoted the production of short-chain fatty acids (SCFAs). Notably, SQLE-M normalized the intestinal barrier dysfunction and metabolic disorders by activating the PI3K/Akt signaling pathway, inhibiting NF-κB-mediated inflammatory responses, and upregulating aquaporin 3 (AQP3) expression. Collectively, SQLE mitigates SDS, which may be associated with alterations in the gut microbiota-metabolite axis and the PI3K/Akt/NF-κB/AQP3 signaling pathway, offering new perspectives for developing spleen-strengthening functional foods derived from food-medicine homologous resources. Download: Download high-res image (462KB) Download: Download full-size image

Rosmarinic acid inhibits cell proliferation, migration, and invasion and induces apoptosis in human glioma cells

Yunsheng Liu,Xiangping Xu,Han Tang,Yuchen Pan,Bing Hu,Guodong Huang

There is a growing evidence that Fyn kinase is upregulated in glioblastoma multiforme (GBM), where it plays a key role in tumor proliferation and invasion. In the present study, the antitumor effects of rosmarinic acid (RA), a Fyn inhibitor, were explored in human‑derived U251 and U343 glioma cell lines. These cells were treated with various concentrations of RA to determine its effects on proliferation, migration, invasion, apoptosis, and gene and protein expression levels. The CCK‑8 assay revealed that RA significantly suppressed cell viability of U251 and U343 cells. Furthermore, RA significantly reduced proliferation rates, inhibited migration and invasion, and decreased the expression levels of invasion‑related factors, such as matrix metalloproteinase (MMP)‑2 and MMP‑9. TUNEL staining revealed that RA resulted in a dose‑dependent increase of U251 and U343 cell apoptosis. In line with this finding, the expression of apoptosis suppressor protein Bcl‑2 was downregulated and that of the pro‑apoptotic proteins Bax and cleaved caspase‑3 was increased. In addition, it was revealed that the phosphatidylinositol 3‑kinase (PI3K)/Akt/nuclear factor‑κB (NF‑κB) signaling pathway was involved in RA‑induced cytotoxicity in U251 and U343 cells. Collectively, the present study suggested RA as a drug candidate for the treatment of GBM.

The ameliorating effects of Guizhi Fuling Wan combined with rosiglitazone in a rat ovarian model of polycystic ovary syndrome by the PI3K/AKT/NF-κB and Nrf2/HO-1 pathways

Yongju Ye,Weimei Zhou,Yuefang Ren,Jiali Lu,Aixue Chen,Ruiying Jin,Feilan Xuan

The Flavonoid Extract of Polygonum viviparum L. Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis by Regulating Intestinal Flora Homeostasis and Uric Acid Levels Through Inhibition of PI3K/AKT/NF-κB/IL-17 Signaling Pathway

Haoyu Liu,Zhen Yang,Qian Chen,Hongjuan Zhang,Yu Liu,Di Wu,Dan Shao,Shengyi Wang,Baocheng Hao

Chronic inflammatory bowel disease, ulcerative colitis (UC), currently lacks specific drugs for clinical treatment, and screening effective therapeutic agents from natural plants represents a critical research strategy. This study aimed to investigate the therapeutic potential of the flavonoid extract of Polygonum viviparum L. (TFPV) against UC. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical components of TFPV, while cell and animal models were employed to evaluate its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation. The mechanism of anti-inflammatory action was further investigated using a mouse model of UC induced by dextran sulfate sodium (DSS). The results revealed the identification of 32 bioactive components in TFPV, with major compounds such as kaempferol, luteolin, galangin, and quercetin. TFPV effectively mitigated inflammatory damage induced by LPS in IPEC-J2 cells and C57BL/6 mice. In the UC modeled by DSS, TFPV attenuated intestinal inflammation by reducing pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; increasing the anti-inflammatory cytokine IL-10; up-regulating tight junction protein expression such as Claudin-1, Occludin, and ZO-1; and inhibiting the expression of PI3K, AKT, NF-κB, and IL-17 proteins. Analysis of mice fecal samples through 16S rRNA gene sequencing demonstrated that TFPV adjusted the equilibrium of gut microbiota by boosting the abundance of Dubosiella and diminishing that of Enterococcus , Romboutsia , and Enterobacter . Untargeted metabolomics analysis further revealed that TFPV reduced inosine and ADP levels while increasing dGMP levels by the regulation of purine metabolism, ultimately resulting in decreased uric acid levels and thereby alleviating intestinal inflammation. Additionally, TFPV safeguarded the intestinal mucosal barrier by enhancing the expression of tight junctions. In conclusion, TFPV alleviates UC by blocking the PI3K/AKT/NF-κB and IL-17 signaling pathways, lessening intestinal inflammation and injury, safeguarding intestinal barrier integrity, balancing gut microbiota, and lowering uric acid levels, suggesting its promise as a therapeutic agent for UC.

Pi-Pa-Run-Fei-Tang alleviates lung injury by modulating IL-6/JAK2/STAT3/IL-17 and PI3K/AKT/NF-κB signaling pathway and balancing Th17 and Treg in murine model of OVA-induced asthma

Xiao-Lu Jie,Zi-Rui Luo,Jin Yu,Zhe-Ren Tong,Qiao-Qiao Li,Jia-Hui Wu,Yi Tao,Pei-Shi Feng,Ji-Ping Lan,Ping Wang

Ethnopharmacological relevance Pi-Pa-Run-Fei-Tang (PPRFT) is an empirical TCM prescription for treating asthma. However, the underlying mechanisms of PPRFT in asthma treatment have yet to be elucidated. Recent advances have revealed that some natural components could ameliorate asthma injury by affecting host metabolism. Untargeted metabolomics can be used to better understand the biological mechanisms underlying asthma development and identify early biomarkers that can help advance treatment. Aim of the study The aim of this study was to verification the efficacy of PPRFT in the treatment of asthma and to preliminarily explore its mechanism. Materials and methods A mouse asthma model was built by OVA induction. Inflammatory cell in BALF was counted. The level of IL-6, IL-1β, and TNF-α in BALF were measured. The levels of IgE in the serum and EPO , NO , SOD , GSH-Px, and MDA in the lung tissue were measured. Furthermore, pathological damage to the lung tissues was detected to evaluate the protective effects of PPRFT. The serum metabolomic profiles of PPRFT in asthmatic mice were determined by GC-MS. The regulatory effects on mechanism pathways of PPRFT in asthmatic mice were explored via immunohistochemical staining and western blotting analysis. Results PPRFT displayed lung-protective effects through decreasing oxidative stress, airway inflammation , and lung tissue damage in OVA-induced mice, which was demonstrated by decreasing inflammatory cell levels, IL-6, IL-1β, and TNF-α levels in BALF, and IgE levels in serum, decreasing EPO, NO, and MDA levels in lung tissue, elevating SOD and GSH-Px levels in lung tissue and lung histopathological changes. In addition, PPRFT could regulate the imbalance in Th17/Treg cell ratios, suppress RORγt, and increase the expression of IL-10 and Foxp3 in the lung. Moreover, PPRFT treatment led to decreased expression of IL-6, p-JAK2/Jak2, p-STAT3/STAT3, IL-17, NF-κB, p-AKT/AKT, and p-PI3K/PI3K. Serum metabolomics analysis revealed that 35 metabolites were significantly different among different groups. Pathway enrichment analysis indicated that 31 pathways were involved. Moreover, correlation analysis and metabolic pathway analysis identified three key metabolic pathways: galactose metabolism; tricarboxylic acid cycle; and glycine, serine , and threonine metabolism. Conclusion This research indicated that PPRFT treatment not only attenuates the clinical symptoms of asthma but is also involved in regulating serum metabolism. The anti-asthmatic activity of PPRFT may be associated with the regulatory effects of IL-6/JAK2/STAT3/IL-17 and PI3K/AKT/NF-κB mechanistic pathways.

Pu-erh tea alleviated colitis-mediated brain dysfunction by promoting butyric acid production

Shanshan Hu,Zhiyuan Lin,Sibo Zhao,Bowen Zhang,Liyong Luo,Liang Zeng

Brain inflammation develops with increased colitis . Pu-erh tea is considered a potential dietary intervention to improve colitis. However, it's unclear whether Pu-erh tea helps alleviate colitis-mediated brain dysfunction . Here, we found that colitis triggered brain dysfunction and increased the risk of depression. Pu-erh tea improved gut-brain barrier function (increased ZO-1 and Occludin) and restored short-chain fatty acids (SCFAs) as well as neurotransmitter release (γ-GABA, 5-HT, and dopamine), which stemmed from the production of butyric acid (BA). Pu-erh tea and BA promoted the production of SCFAs by reshaping the gut microbes (increased Lactobacillus , Akkermansia , Faecalibaculum ), thereby downregulating gut inflammatory protein expression (PI3K/AKT/NF-κB). SCFAs, especially BA, intervened directly in the blood-brain barrier via the gut-brain axis to restore neurotransmitter release. Collectively, our results highlighted that increasing BA through Pu-erh tea consumption may be a key mechanism for improving colitis-mediated brain dysfunction by lowering gut inflammation and balancing gut microbe-gut-brain axis homeostasis . These results provide a promising step that might encourage further investigations of Pu-erh tea as a protective agent for brain function in colitis patients.

A genetically engineered “reinforced concrete” scaffold regulates the N2 neutrophil innate immune cascade to repair bone defects

Wenxiao Shi,Yu Feng,Jincheng Tang,Yichang Xu,Wang Wei,Lichen Zhang,Xinzhao Jiang,Zhouye Ding,Kun Xi,Liang Chen,Yong Gu

The innate immune response is crucial to the inflammation, but how neutrophils and macrophages act in bone repair and tissue engineering treatment strategies await clarification. In this study, we found N2 neutrophils release stronger “eat me” signals to induce macrophage phagocytosis which then polarize into the M2c anti-inflammatory phenotype. This is beneficial for bone repair. Guided by this biological mechanism, we filled a mesoporous bioactive glass scaffold (MBG) with HAMA hydrogel loaded with TGFβ1 adenovirus (Ad@H), constructing a genetically engineered composite scaffold (Ad@H/M). The scaffold not only has good hydrophilicity and biocompatibility, but also provides mechanical stress support for bone repair. Adenovirus infection quickly induces N2 neutrophils, upregulating NF-κB and MAPK signaling pathways through Toll-like receptor 4 (TLR4) to promote the inflammatory response and macrophage phagocytosis. Macrophages perform phagocytosis and polarize towards the M2 phenotype, mediating the inflammatory response by inhibiting the PI3K-AKT-NF-κB pathway, maintaining homeostasis of the osteogenic microenvironment. The role of Ad@H/M scaffold in regulating early inflammation and promoting long-term bone regeneration was further validated in vivo. In brief, this study focuses on the cascade of reactions between neutrophils and macrophage subtypes, and reports a composite scaffold that coordinates the innate immune response to promote bone repair. This article is protected by copyright. All rights reserved