Food Science and Human Wellness
·
2023
·
IF 7
Qihong Jiang,Lin Chen,Rui Wang,Yin Chen,Shanggui Deng,Guoxin Shen,Shulai Liu,Xingwei Xiang
Type 2 diabetes mellitus (T2DM) is a complex metabolic disease threatening human health. We investigated the effects of Tegillarca granosa polysaccharide (TGP) and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin. TGP (5.1 × 10 3 Da) was composed of mannose, glucosamine, rhamnose, glucuronic acid, galactosamine, glucose, galactose, xylose, and fucose. It could significantly alleviate weight loss, reduce fasting blood glucose levels, reverse dyslipidemia, reduce liver damage from oxidative stress, and improve insulin sensitivity. RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance. TGP increased the abundance of Allobaculum , Akkermansia , and Bifidobacterium , restored the microbiota abundance in the intestinal tracts of mice with T2DM, and promoted short-chain fatty acid production. This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.
研究领域:
营养保健品
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内分泌学
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分子生物学
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微生物组研究
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Bio Materials
·
2025
·
IF 4.7
Dong Fan,Zhongyu Wang,Xingyi Yuan,Shixue Luo,Runsi Zhan,Weiyu Hu,Huitong Chen,Weiwen Wang,Jing Liu,Zongming Wang,Xin Wang
Aims Nonfunctioning pituitary adenomas (NFPAs) are a common intracranial tumor in clinical practice, and currently available treatments for NFPA include surgical resection and radiotherapy. However, this is due to the relatively high risk of recurrence and persistent side effects of these therapies. As a local treatment, photodynamic therapy (PDT) shows promise in solid tumors through spatiotemporally controlled cytotoxicity. The aim of this study was to investigate the mechanism of action of photosensitizer Ru2 in NFPA. Materials and methods [Ru(tpy)(tpy-Br)] (PF6)2 was synthesized from Ru(tpy)Cl3, and further synthesized into Ru2. Cell viability of Light+Ru2 or Dark+Ru2 was assayed using the CCK-8 assay and live–dead cell staining. RNA-seq of Light+Ru2-treated PDFS cells yielded differentially expressed genes. The expression of PI3K/ATK/P53 was detected using qPCR, Western blot. PI3K agonist 740Y–P and AKT agonist SC79 were added for further pathway validation. The effect of PDT on PDFS cell viability by 3D multicellular tumor spheroids (MCTSs) was evaluated. Key findings We untangle that Ru2-PDT specifically activates the p53 pathway and inhibits PI3K/AKT phosphorylation in PDFS cells. Under 595 nm illumination, Ru2 activates p53 and induces cell cycle arrest in the G0/G1 phase. Simultaneously, Ru2-PDT significantly suppressed the phosphorylation of the PI3K/AKT signaling pathway. Further investigation reveals that the PI3K/AKT agonist treatment partially inhibits p53 expression, alleviates Ru2-PDT-induced apoptosis, and reverses its inhibitory effects on PDFS cell migration and invasion. Significance This study, for the first time, elucidates the molecular mechanism of Ru2-PDT targeting the PI3K/AKT/p53 signaling axis, providing a theoretical basis for the clinical treatment of nonfunctioning pituitary adenomas.
研究领域:
肿瘤学
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神经外科
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分子生物学
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药理学
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生物化学
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医学科学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2025
·
IF 4
Ping Jiang,Yanfei He,Guangpei Xu,Chuanbo Sun
This study aims to evaluate the mechanism of RCH against CCl 4 -induced liver injury in mice. RCH treatment effectively inhibited CCl 4 -induced liver injury and apoptosis in mice, and reduced liver enzyme activities, blood inflammatory cell and serum inflammatory factor levels. Network pharmacology and machine learning predicted that PI3K-Akt pathway and Met proteins play important roles in RCH anti-CCl 4 -induced liver injury. The results of qRT-PCR and Western blot showed that RCH could down-regulate the expression of the receptor proteins Met, Tlr2, and Tlr4, and inhibit the phosphorylation of Pik3ca and Akt1, and prevent the phosphorylation of NF-κB P65, and decrease cleaved Caspase3 expression. These findings suggest that RCH effectively alleviated liver injury in CCl 4 -induced mice by inhibiting the Met/Tlr2/Tlr4-mediated PI3K-Akt signaling pathway.
研究领域:
药理学
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分子生物学
✓ 已验证
DOI
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2022
·Vol. 37
·期 8
·1840-1852
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IF 4.109
Huijie Chen,Yue Zhang,Mengmeng Zou,Xiaowei Sun,Xiaodan Huang,Shiwen Xu
Dibutyl phthalate (DBP) is a phthalic acid ester (PAE) that has posed a health hazard to the organisms. Naringenin (NRG) is a flavanone compound that has shown protection against several environmental chemicals through suppression of oxidative stress and activation of phosphatidylinositol 3-kinase/threonine kinase (PI3K/AKT) signaling pathway. Herein, swine testis (ST) cells were treated with 1.8 μM of DBP or/and 25.39 nM of NRG for 24 h, we described the discovery path of NRG inhibition on apoptosis in DBP-exposed ST cells through targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN). We first found that the anti-apoptosis effect of NRG is dependent on mitochondrial pathway through flow cytometry and related gene/protein expression, and then we detected PI3K/AKT pathway-related gene/protein expression, and established a computational docking assay between NRG and PTEN. We found that NRG specifically binds to three basic residues (His93, Lys125, Lys128) of P loop in PTEN, as well as phosphatase domains (Asp92, His93, Cys124, Lys125, Ala126, Lys128, and Arg130) in active dephosphorylation pockets, thereby reducing PTEN level and activating PI3K/AKT signaling pathway, and further inhibiting oxidative stress and mitochondrial pathway apoptosis. Taken together, our results push forward that NRG deserves further attention as a potential antagonistic therapy against DBP through targeting PTEN to inhibit oxidative stress and activate PI3K/AKT signaling pathway.
研究领域:
毒理学
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细胞生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2019
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IF 3.17
Jihang Dai,Yu Sun,Duoyun Chen,Yaxin Zhang,Lianqi Yan,Xiaolei Li,Jingcheng Wang
Fibroblasts excessive proliferation was considered as a decisive reason for epidural fibrosis , which was known as a serious complication of lumbar laminectomy. As a traditional Chinese medicine , triptolide (TP) was used to be proved effective in preventing several fibrosis scar formation diseases. However, little is known about the effect of TP on preventing epidural fibrosis and its possible mechanism. Here, we performed in vitro and in vivo experiments to detect the possible mechanism of TP in preventing epidural fibrosis. In vitro, the effect of TP on impacting fibroblasts proliferation activities was detected by CCK-8, cell cycle assay and EdU incorporation assay. Also, the expressions of cell proliferation protein markers and the expressions of p-PI3K, p-AKT, p-mTOR were detect by Western blot . Besides, the effect of TP on inducing fibroblast apoptosis and autophagy was tested by Western blots, flow cytometry, TUNEL staining , Transmission electron microscope (TEM) analysis and LC3 immunofluorescent staining. The results suggested that TP could suppress the activation of PI3K/AKT/mTOR signaling pathway. Meanwhile, TP could inhibit fibroblast proliferation and induce fibroblast apoptosis as well as autophagy, which was known as two cellular self-destructions. Furthermore, we speculated the possible molecular pathway, through which that TP could inhibit fibroblast proliferation, induce fibroblast apoptosis and autophagy. We used PI3-kinase activator (740Y-P) to activate the PI3K/AKT/mTOR signaling. Activation of PI3K/AKT/mTOR signaling pathway increase the proliferation of fibroblasts and suppressed the autophagy and apoptosis induced by TP. In vivo, we built epidural fibrosis models in rats and locally applied TP of various concentrations. Hematoxylin–eosin (HE) and Masson's trichrome were used to detect the effect of TP on reducing epidural fibrosis. And the results showed that TP could significantly reduce the surgery-induced epidural fibrosis. In conclusion, the results above shown that TP could reduce epidural fibrosis formation, and the potential mechanism might through inhibiting fibroblast proliferation and stimulating apoptosis and autophagy via suppressing PI3K/AKT/mTOR signaling pathway. It might provide a novel thought for reducing surgery-induced epidural fibrosis.
研究领域:
药理学
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神经外科
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2025
·
IF 8.1
Wen Zhuohao,Li Shuyi,Qiu Huiguo,Liu Xueyan,You Zhiying,Yan Yuhan,Che Yuejuan,Zhou Miao
Periosteum plays an indispensable role in bone regeneration by providing osteogenic and angiogenic cues essential for tissue repair. In cases of severe bone defects or nonunion, autologous vascularized periosteum transplantation remains a highly effective clinical solution. However, its application is restricted by donor site morbidity and limited tissue availability, thereby underscoring the urgent need for artificial periosteum that mimics both the composition and structure of the native counterpart. Among these properties, the topological morphology of the periosteum is believed to be critical, yet its influence on bone regeneration remains insufficiently understood. In this study, biomimetic periosteum membranes composed of coaxially electrospun poly(ε-caprolactone) (PCL) and periosteal extracellular matrix (pECM) were fabricated with either random or aligned nanofiber architectures. Their osteogenic potential was systematically evaluated in vitro and in vivo. Compared to the randomly arranged structure, aligned pECM (aPEC) significantly enhanced the adhesion, alignment, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by activating the ITGB1/PI3K/AKT signaling pathway, whereas these effects were not observed in pure PCL membranes. These findings demonstrate that aligned topological morphology in biomimetic periosteum plays a pivotal role in directing stem cell behavior and promoting bone regeneration. This work provides mechanistic insight and technical guidance for the future design of functionally enhanced artificial periosteum for bone tissue engineering applications.
研究领域:
组织工程
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生物材料学
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分子生物学
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再生医学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
OncoTargets and Therapy
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2022
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IF 4.345
Ping Chen,Xiaoyong Zhao,Hui Wang,Mengdan Zheng,Qinghua Wang,Wenjuan Chang
Purpose LncRNAs are important regulators in cancers. In this study, we investigated the role of lncRNA PCAT18 in gastric cancer (GC).Patients and Methods The level of PCAT18 in GC tissues and cells was determined by qRT-PCR. The cellular behaviors of GC cells with knockdown or overexpression of PCAT18 were respectively detected by CCK-8 assays, colony formation assays, flow cytometry and Western blot. A GC mice model was established by subcutaneous injection of MGC-803 and HGC-27 cells with the knockdown or overexpression of PCAT18. The tumor size and weight were measured, and IHC was performed to determine ki-67 level. Predicted by bioinformatics software and confirmed by dual-luciferase reporter assay, PCAT18 was involved in miR-107/PTEN axis, thus, the expression of and relationship among PCAT18, miR-107 and PTEN pathway were explored in clinical cases and GC cell lines. Rescue assay was performed in GC cells by co-transfection with miR-107 mimic or PCAT18. The PTEN/PI3K/AKT pathway was then detected by Western blot.Results PCAT18 was down-regulated in GC tissues and cells, and it had a significant diagnostic value for GC. The expression of PCAT18 was highly associated with tumor size, and PCAT18 was found to inhibit GC growth in vitro and in vivo. It was also found that PCAT18 was involved in PTEN/PI3K/AKT signaling pathway through targeting miR-107.Conclusion PCAT18 inhibits the progression of GC via miR-107/PTEN/PI3K/AKT signaling pathway. Additionally, PCAT18 is possibly a promising target for treatment of GC.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Neuroinflammation
·
2024
·Vol. 21
·期 1
·1-16
·
IF 9.3
Chen Lushu,Zhang HuiYing,Zhang Ying,Li Xiumiao,Wang MeiHuan,Shen Yaming,Cao Yuan,Xu Yong,Yao Jin
Retinal neovascularisation is a major cause of blindness in patients with proliferative diabetic retinopathy (PDR). It is mediated by the complex interaction between dysfunctional ganglion cells, microglia, and vascular endothelial cells. Notably, retinal microglia, the intrinsic immune cells of the retina, play a crucial role in the pathogenesis of retinopathy. In this study, we found that lysophosphatidylserines (LysoPS) released from injured ganglion cells induced microglial extracellular trap formation and retinal neovascularisation. Mechanistically, LysoPS activated the GPR34-PI3K-AKT-NINJ1 signalling axis by interacting with the GPR34 receptor on the microglia. This activation upregulated the expression of inflammatory cytokines, such as IL-6, IL-8, VEGFA, and FGF2, and facilitated retinal vascular endothelial cell angiogenesis. As a result, inhibition of the GPR34-PI3K-AKT-NINJ1 axis significantly decreased microglial extracellular trap formation and neovascularisation by suppressing LysoPS-induced microglial inflammatory responses, both in vitro and in vivo. This study reveals the crucial role of apoptotic ganglion cells in activating microglial inflammation in PDR, thereby enhancing our understanding of the pathogenesis of retinal neovascularisation.
研究领域:
眼科学
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免疫学
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOSCIENCE REPORTS
·
2021
·Vol. 41
·期 10
·
IF 3.84
Wang Yingying,Hou Yongqiang,Hou Lanjiao,Wang Wei,Li Ke,Zhang Zhe,Du Bo,Kong Dexin
Lung cancer remains the leading cause of cancer mortality because of its metastatic potential and high malignancy. The discovery of new applications for old drugs is a shortcut for cancer therapy. We recently investigated the antitumor effect of digoxin, a well-established drug for treating heart failure, against nonsmall cell lung cancer A549 and H1299 cells. Digoxin inhibited the proliferation and colony-forming ability of the two cell lines and arrested the cell cycle at the G0/G1 phase in A549 cells and the G2/M phase in H1299 cells. Mitochondria-mediated apoptosis was induced in A549 cells but not in H1299 cells after treatment with digoxin. Moreover, digoxin inhibited the migration, invasion, adhesion and epithelial–mesenchymal transition of A549 and H1299 cells. Autophagy was induced in both cell lines after treatment with digoxin, with an increase in autophagosome foci. In addition, digoxin inhibited the phosphorylation of Akt, mTOR and p70S6K, signaling molecules of the PI3K/Akt pathway that are known to be involved in tumor cell survival, proliferation, metastasis and autophagy. Our findings suggest that digoxin has the potential to be used for therapy for human nonsmall cell lung cancer, but further evidence is required.
研究领域:
肿瘤学
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药理学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
RENAL FAILURE
·
2022
·
IF 3.222
Qi Xiao
Background To prove the internal connection, we deciphered the effect of cinnamaldehyde on kidney senescence through establishing animal and cell models.Methods In vivo, a rat senescence model was constructed using D-galactose (D-gal), and the modeled rats were further treated with cinnamaldehyde. In vitro, rat renal tubular epithelial cells (NRK-52E) were transfected with miR-155 mimic or inhibitor and then treated with cinnamaldehyde, D-gal or PI3K inhibitor (LY294002). The serum levels of blood urea nitrogen (BUN) and serum creatinine (Scr) of the rats were measured by an automatic biochemical analyzer. Pathological changes of kidney were determined by hematoxylin-eosin staining. The senescence and viability of NRK-52E cells were assessed by SA-β-gal staining and CCK-8 assay, respectively. The levels of miR-155, p-PI3K/PI3K, p-Akt/Akt, LC3B (LC3-II and LC3-I) and Beclin1 were detected by qRT-PCR, immunohistochemistry, or western blot.Results D-gal elevated the levels of BUN, Scr and miR-155 in the kidney, induced the renal pathological damage, inhibited the cell viability, increased the numbers of SA-β-gal-, LC3B- and Beclin1-positive cells and upregulated the levels of LC3-II/LC3-I and Beclin1 both in the kidney and cells. Cinnamaldehyde reversed D-gal-induced effects on the kidney and cells, and moreover, the cinnamaldehyde-induced anti-D-gal effects on cells could be suppressed by miR-155 mimic but promoted by miR-155 inhibitor. LY294002 potentiated D-gal-induced effects, and reversed cinnamaldehyde- and miR-155 inhibitor-caused impacts on the PI3K/Akt pathway and LC3-II/LC3-I level in D-gal-induced cells.Conclusion Cinnamaldehyde attenuates kidney senescence and injury through PI3K/Akt pathway-mediated autophagy via downregulating miR-155.
研究领域:
药理学
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分子生物学
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肾病学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Ying Ren,Xiangka Hu,Mushuang Qi,Wanjun Zhu,Jin Li,Shuyu Yang,Chunmei Dai
Background Diabetes is a metabolic disease characterized by hyperglycaemia. Tangningtongluo Tablet (TNTL) is an inpatient formula extensively utilized to treat diabetes mellitus (DM), but the protective mechanism is not clear. This study aimed to investigate the relevant mechanisms by which TNTL affects pancreatic damage in diabetic mice and autophagy. Methods The impact of TNTL on pancreatic damage in diabetic mice in vitro and in vivo was investigated via glucose and lipid metabolism analyses, HE staining, CCK-8, TUNEL staining, Annexin V/PI, and Western blotting. Molecular docking and Western blotting were used to verify the results of network pharmacological analysis, which was carried out to explore the mechanism by which TNTL affects DM. The autophagosome levels were visualized via RFP-GFP-LC3 and transmission electron microscopy, and lysosomal function was evaluated via Lysotracker red staining. Western blot, immunohistochemistry and immunofluorescence staining were used to detect the expression of the autophagy proteins LC3, p62 and LAMP2. Results Compared with the model group, TNTL protected pancreas from oxidative stress, decreased the level of MDA, increased the levels of SOD and GSH-px, induced the occurrence of autophagy and decreased the levels of apoptotic factors. Moreover, TNTL inhibited the protein expression of p-PI3K, p-Akt and p-mTOR, increased the levels of LC3 and LAMP2 and decreased the level of p62, and the autophagy inhibitor CQ blocked the protective effect of TNTL on pancreatic damage in diabetic mice. Conclusion These results demonstrated that TNTL ameliorated pancreatic damage in diabetic mice by inhibiting the PI3K/Akt/mTOR signaling and regulating autophagy.
研究领域:
药理学
·
糖尿病
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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
JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Min Liu,Hongqiu Zhu,Ying Zhu,Xiaodan Hu
Ethnopharmacological relevance Guizhi Fuling Wan (GFW) is a traditional Chinese medicine used to remove blood stasis and dissipate phlegm for treating gynecological diseases that was invented by Zhang Zhongjing in the Eastern Han dynasty. In recent years, GFW has been widely used to treat patients with polycystic ovary syndrome (PCOS). Clinical and animal studies have shown that it is effective in the treatment of PCOS, but its mechanism is unknown. Generally, it works by regulating autophagy via the PI3K/AKT/mTOR signaling pathway. Aim of the study This study investigated the effects and mechanism of GFW in PCOS rats with insulin resistance (IR) in order to provide better understanding of its observed clinical effects and a theoretical basis for the study of traditional Chinese medicine. Materials and methods Eighty-four female Sprague–Dawley rats were randomly divided into seven groups (n = 12 per group): 1) control, 2) PCOS model, 3) low-dose GFW, 4) medium-dose GFW, 5) high-dose GFW, 6) metformin , and 7) medium-dose GFW plus LY294002 . In all non-control groups, we induced PCOS through daily letrozole combined with intragastric high-fat emulsion for 21 days. After treatment, rats were sacrificed and serum follicle-stimulating hormone (FSH), testosterone (T), progesterone , luteinizing hormone (LH), 17β-estradiol, fasting insulin (FINS), and fasting plasma glucose levels were measured by enzyme-linked immunosorbent assay (ELISA). The LH/FSH ratios and HOMA-IR values were calculated. Ovarian morphology was observed by hematoxylin and eosin staining, and all follicles were counted under a microscope. MDC-positive vesicles were used as markers to detect autophagy, and the expression levels of p62, Beclin1 , and LC3-II were examined by immunostaining. Western blotting was used to measure PI3K/AKT/mTOR pathway activation, granulosa cell apoptosis , and autophagy. Results Compared with the PCOS model group, GFW-treated rats had less atretic and cystic follicles, and more mature follicles and corpus lutea. The GFW-treated rats had lower serum T, LH, and FINS levels than the PCOS model group, as well as lower LH/FSH ratios and HOMA-IR values. GFW treatment resulted in significantly reduced levels of cleaved-Caspase-3, cleaved-Caspase-9, BAX, Beclin1, Atg5, and LC3-II. Phosphorylation of PI3K, AKT, and mTOR was significantly higher in GFW-treated rats compared with the PCOS model group. The phosphorylation of PI3K, AKT, and mTOR was decreased with the use of a PI3K antagonist. Conclusions Our results indicate that GFW inhibited granulosa cell autophagy and promoted follicular development to attenuate ovulation disorder in PCOS-IR rats. This was associated with activation of the PI3K/AKT/mTOR signaling pathway.
研究领域:
药理学
·
中医药
·
内分泌学
·
生殖生物学
✓ 已验证
DOI
PubMed
高影响因子
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