Materials Today Bio
·
2022
·
IF 10.761
Lili Liu,Xianjing Li,Wenhuan Bu,Nianqiang Jin,Yuan Meng,Yi Wang,Duan Wang,Xiaowei Xu,Ding Zhou,Hongchen Sun
Pulp injury is one of the most common clinical diseases, and severe cases are usually associated with the functional loss of the tooth, while the current clinical treatment modality is only a cavity filling procedure without the regeneration of the dentin-pulp complex, thus leading to a devitalized and brittle tooth. In this study, carbon dots (CDots) with excellent biocompatibility are prepared from ascorbic acid and polyethyleneimine via a hydrothermal method. The as-prepared CDots can enhance extracellular matrix (ECM) secretion of human dental pulp stem cells (DPSCs), giving rise to increased cell adhesion on ECM and a stronger osteogenic/odontogenic differentiation capacity of DPSCs. Further, the mechanism underlying CDots-enhanced ECM secretion is revealed by the transcriptome analysis, Western blot assay and molecular dynamics simulation, identifying that the pharmacological activities of CDots are originated from a reasonable activation of the autophagy, which is mediated by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway. Based on the abundant CDots-induced ECM and thereby the reinforcement of the cell-ECM adhesion, an intact dental pulp stem cell sheet can be achieved, which in return promote in vivo the efficient regeneration of dentin-pulp complex as well as blood vessels.
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高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2021
·Vol. 37
·期 1
·101-119
·
IF 4.119
Caixia Wang,Zhangyu Gu,Xueyan Gu,Xinyue Tan,Shuang Wang,Rui Zhang,Ruifen Li,Mingkun Sun,Chunyan Gui,Sheng Li,Yixing Ye,Jianhua Ma,Li Su,Changhao Liang
The aim of this study was to investigate the protective effects of Nano-Se against nickel (Ni)-induced hepatotoxicity and the potential mechanism. Hence, we constructed in vivo and in vitro models of Ni-induced hepatotoxicity. Sprague–Dawley (SD) rats were exposed to nickel sulfate (NiSO 4 , 5.0 mg/kg, i.p.) with or without Nano-Se (0.5, 1, and 2 mg/kg, oral gavage) co-administration for 14 days, and HepG2 cells were exposed to NiSO 4 (1500 μM) with or without Nano-Se (20 μM) for 24 h. Nano-Se obviously prevented Ni-induced hepatotoxicity indicated by ameliorating pathological change and decreasing Ni accumulation in rat livers. Ni induced a significant increase in hepatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSH-Px), and malondialdehyde (MDA) level, decreased the glutathione (GSH) content while compared to those in the control group. Nano-Se administration improved the hepatic antioxidant capacity through increase hepatic GSH contents and GSH-Px activity, decrease the activities of SOD, CAT, and MDA level. Nano-Se improved the cell viability, decreased active oxygen (ROS) generation and ameliorated morphological changes of nuclear structures in Ni-treated HepG2 cells. In addition, Nano-Se inhibited the Ni-induced increases of cytochrome c, caspase-9, cleaved caspase-3, increased PI3K and AKT phosphorylation both in vivo and in vitro. Besides, the PI3K inhibitor Y294002 could inhibit the protective effects of Nano-Se on apoptosis. Thus, Nano-Se significantly activates PI3K/AKT signaling to ameliorate apoptosis in Ni-induced hepatotoxicity.
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MOLECULAR MEDICINE
·
2021
·Vol. 27
·期 1
·1-16
·
IF 6.354
Cui Jing,Guo Yao,Wu Heshui,Xiong Jiongxin,Peng Tao
Background Gemcitabine (GEM) resistance remains a significant clinical challenge in pancreatic cancer treatment. Here, we investigated the therapeutic utility of everolimus (Evr), an inhibitor of mammalian target of rapamycin (mTOR), in targeting the Warburg effect to overcome GEM resistance in pancreatic cancer. Methods The effect of Evr and/or mTOR overexpression or GEM on cell viability, migration, apoptosis, and glucose metabolism (Warburg effect) was evaluated in GEM-sensitive (GEM sen ) and GEM-resistant (GEM res ) pancreatic cancer cells. Results We demonstrated that the upregulation of mTOR enhanced cell viability and favored the Warburg effect in pancreatic cancer cells via the regulation of PI3K/AKT/mTOR signaling. However, this effect was counteracted by Evr, which inhibited aerobic glycolysis by reducing the levels of glucose, lactic acid, and adenosine triphosphate and suppressing the expression of glucose transporter 1, lactate dehydrogenase-B, hexokinase 2, and pyruvate kinase M2 in GEM sen and GEM res cells. Evr also promoted apoptosis by upregulating the pro-apoptotic proteins Bax and cytochrome-c and downregulating the anti-apoptotic protein Bcl-2. GEM was minimally effective in suppressing GEM res cell activity, but the therapeutic effectiveness of Evr against pancreatic cancer growth was greater in GEM res cells than that in GEM sen cells. In vivo studies confirmed that while GEM failed to inhibit the progression of GEM res tumors, Evr significantly decreased the volume of GEM res tumors while suppressing tumor cell proliferation and enhancing tumor apoptosis in the presence of GEM. Conclusions Evr treatment may be a promising strategy to target the growth and activity of GEM-resistant pancreatic cancer cells by regulating glucose metabolism via inactivation of PI3K/AKT/mTOR signaling.
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PHYTOMEDICINE
·
2020
·
IF 4.268
Xin Shan,Jing Chen,Shilin Dai,Jie Wang,Zhiheng Huang,Zhiyang Lv,Qian Wang,Qinan Wu
Background Cyanidin (CY) is one of the most abundant anthocyanidins found in red-purple diet sources such as grapes, blueberries and purple corns . CY has been proven to exhibit a wide range of biological functions including antioxidant, antiviral, anticarcinogenic and anti-inflammatory properties. Purpose This study investigated the anti-depressive activity of CY and its related mechanism. Methods In the behavioral tests, CY-related effects on depressive symptoms were evaluated. Then the changes in PI3K/AKT/FOXG1/FGF-2 signaling and adult neurogenesis including doublecortin (DCX+) cell number, dendritic length, secondary and third dendrites number in the hippocampus were investigated by Immunofluorescence and Western blot analyses. PI3K antagonist LY 294,002 was used to verify the unique impact of PI3K/AKT/FoxG1/FGF-2 signaling on CY-related antidepressant efficacy. Results CY grossly reversed CUMS-induced behavioral defects, The DCX+ cell number and protein levels increased in CUMS mice receiving CY administration. LY 294,002 successfully blocked CY-induced improvements in depressive behaviors, neurogenesis, and protein levels in CUMS mice. Conclusion The findings demonstrated that CY was efficacious in alleviating depression-like symptoms, which was dependent on PI3K/AKT/FoxG1/FGF-2 signaling-modulated neurogenesis enhancement.
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OncoTargets and Therapy
·
2022
·
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.
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高影响因子
JOURNAL OF CLINICAL LABORATORY ANALYSIS
·
2022
·Vol. 36
·期 7
·e24406
·
IF 3.124
Zhihai Li,Qiaozhi Jin,Yana Sun
Background LINC00941 has been proved to be related to various tumors, but its relationship with laryngocarcinoma remains vague. Methods LINC00941 expression in laryngocarcinoma tumor and laryngocarcinoma cells was determined by real time-quantitative polymerase chain reaction (RT-qPCR). Besides, the five-year survival of laryngocarcinoma patients with different LINC00941 expression was analyzed with Kaplan–Meier survival analysis, and the clinical characteristics of laryngocarcinoma patients were also recorded. After transfection, cell viability, cell proliferation, apoptosis, cell cycle, migration, and invasion were detected by cell counting kit-8 (CCK-8), colony formation, flow cytometry, cell scratch, and Transwell assays, respectively. Glycolysis was assessed by the colorimetric method. Expressions of proliferation-associated proteins, migration-associated proteins, glycolysis-associated proteins, and phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signal pathway-associated proteins were detected by Western blot. Results In laryngocarcinoma tumor tissues and cells, LINC00941 was highly expressed. High expression of LINC00941 decreased the 5-year survival of laryngocarcinoma patients, and it was positively related to lymph node metastasis and clinical stages. LINC00941 overexpression decreased apoptosis but promoted cell viability, proliferation, cell-cycle progression, migration, and invasion, and glucose consumption and lactate production in laryngocarcinoma cells. Moreover, LINC00941 overexpression elevated expressions of Ki-67, PCNA, MMP2, N-Cadherin, HK2, PFKFB4, and PKM, activated the PI3K/AKT/mTOR signal pathway but reduced E-Cadherin expression, while LINC00941 silencing had the opposite effects. PKM overexpression reversed the effects of LINC00941 silencing on cellular and glycolytic phenotypes. Conclusion LINC00941 promoted in vitro progression and glycolysis of laryngocarcinoma cells by upregulating PKM via activating the PI3K/AKT/mTOR signaling pathway.
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Pharmacognosy Magazine
·
2023
·
IF 0.7
Jiang-Long Shi,Li-Yun Liu,Yu-Ting Dong,Tao Shen
BackgroundSeveral studies have demonstrated the anti-inflammatory properties of gastrodin. However, its specific role and mechanism in the context of osteoarthritis (OA) remain unclear.ObjectivesThe objective of this study was to explore the function and mechanism of gastrodin in both in vivo and in vitro OA models.Materials and MethodsIn this study, the targets of gastrodin against osteoarthritis were analyzed using bioinformatics methods. The effect of gastrodin on neutrophil infiltration and inflammatory cytokines in OA synovial tissue was evaluated using H&E staining. The levels of inflammatory cytokines were determined using ELISA and Q-PCR. The extracellular matrix degradation-related proteins and PI3K/AKT/FoxO1 signaling pathway were tested using western blotting.ResultsBioinformatics analysis predicted that the target of gastrodin against OA might act on the FoxO pathway. The use of gastrodin resulted in a significant reduction in the infiltration of neutrophils in the synovial tissue of rats, as observed through H&E staining. Additionally, gastrodin was found to attenuate IL-1β-induced inhibition of chondrocyte viability, pro-inflammatory cytokine production, and extracellular matrix degradation. This effect can be attributed to the suppression of PI3K/AKT/FoxO1 by gastrodin.ConclusionThese findings indicate that gastrodin is a treatment for OA.
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高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2023
·
IF 4.7
Qian Wu,Wenrui Yang,Yanju Bi,Yujie Yao,Chengzhi Li,Xiaojing Li
Chlorpyrifos (CPF), a widely used organophosphate pesticide that has caused large-scale contamination globally, has become a major concern. Baicalein (BAI), as a flavonoid extract, shows anti-inflammatory as well as antioxidant activities . The kidneys of fish serve to excrete toxins and are major target organs for environmental contaminants. However, it is not obvious whether BAI can counteract the damage caused by CPF exposure to fish kidneys . Therefore, we conducted a 30-day simulation of CPF poisoning and/or BAI treatment by adding 23.2 μg/L CPF to water and/or 0.15 g/kg BAI to feed. In the transmission electron microscopy results, we observed obvious phenomenon of autophagy and apoptosis in the CPF group, and the TUNEL staining and immunofluorescence of LC3B and p62 double-staining results confirmed that CPF induced autophagy and apoptosis in the kidney of common carp . Furthermore, CPF induced the increase of ROS level and inhibition of PI3K and Nrf2 pathways, which in turn triggered oxidative stress , autophagy and apoptosis in carp kidney according to western blot , RT-qPCR and kit assays. However, addition of BAI significantly alleviated oxidative stress , autophagy and apoptosis due to binding to PI3K protein. Additionally, through phylogenetic tree and structural domain analyses, we also found that the binding sites of BAI and PI3K are conserved in a variety of representative species. These results suggest that BAI antagonizes CPF-caused renal impairments in carp involving the PI3K/AKT pathway and the Nrf2 pathway. Our findings provide new insights into the nephrotoxicity effects of CPF and the potential use of BAI as a detoxification agent for CPF intoxication.
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Cancer Cell International
·
2021
·Vol. 21
·期 1
·1-13
·
IF 5.722
Zheng Kebin,Xie Haipeng,Wu Wensong,Wen Xichao,Zeng Zhaomu,Shi Yanfang
Background Increasing studies have revealed that circular RNAs (CircRNAs) make great contributions to regulating tumor progression. Therefore, we intended to explore the expression characteristics, function, and related mechanisms of a novel type of circRNA, PIP5K1A, in glioma.Methods Firstly, reverse transcription-polymerase chain reaction (RT-PCR) was carried out to examine CircPIP5K1A expression in glioma tissues and adjacent normal tissues, and the correlation between CircPIP5K1A level and the clinical-pathological indicators of glioma was analyzed. Then, the CircPIP5K1A expression in various glioma cell lines was detected, and CircPIP5K1A overexpression and knockdown cell models were constructed. Subsequently, cell proliferation and viability were detected by the CCK8 method and BrdU staining. Cell apoptosis was detected by flow cytometry, and cell invasion was examined by Transwell assay. The expression of TCF12, PI3K/AKT pathway apoptotic related proteins (Caspase3, Bax, and Bcl2) and epithelial-mesenchymal transition (EMT) markers (E-cadherin, Vimentin, and N-cadherin) was determined by western blot or RT-PCR.Results The results manifested that CircPIP5K1A was upregulated in glioma tissues (compared with that in normal adjacent tissues), and overexpressed CircPIP5K1A was related to glioma volume and histopathological grade. Functionally, overexpressing CircPIP5K1A notably elevated glioma cell proliferation, invasion, and EMT and inhibited apoptosis both in vivo and in vitro. Besides, CircPIP5K1A upregulated TCF12 and PI3K/AKT activation. Bioinformatics analysis testified that miR-515-5p was a common target of CircPIP5K1A and TCF12, while the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) experiment further confirmed that CircPIP5K1A targeted miR-515-5p, which bound the 3′-untranslated region (UTR) of TCF12.Conclusion sOverall, the study illustrated that CircPIP5K1A is a potential prognostic marker in glioma and regulates glioma evolvement by modulating the miR-515-5p-mediated TCF12/PI3K/AKT axis.
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BIOORGANIC CHEMISTRY
·
2023
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IF 5.1
Ren-Fen Ma,Hu Liu,Xue-Chun Zhao,Peipei Shan,Ping Sun,Jun-Juan Xue,Guodong Wei,Hua Zhang
Phytochemical investigation into the leaves and branches of Daphne genkwa afforded 25 meroterpenoids ( 1 – 16 ) including nine pairs of enantiomers ( 1a / 1b − 8a / 8b and 12a / 12b ), among which 20 compounds have been reported in the present work for the first time. The structures with absolute configurations of the new molecules (excluding 10 – 13 ) were established via comprehensive spectroscopic analyses especially electronic circular dichroism (ECD) and Mosher’s methods. A preliminary in vitro cell viability assay revealed remarkable cytotoxicities of selective compounds against A549 (lung), Hela (cervical), MDA-MB231 (breast) and MCF-7 (breast) cancer cells, and compound 8a showed the best inhibitory activity with IC 50 values in the range of 3.12–4.67 μM toward the four cell lines. Subsequent in vitro antitumor evaluation of 8a disclosed that it could inhibit the proliferation and metastasis, as well as induce significant apoptosis and cycle arrest, of A549 cells. Further mechanistic investigations revealed that 8a could exert its antitumor activity via inhibiting the PI3K/Akt/mTOR signaling pathway.
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高影响因子
MOLECULES
·
2023
·Vol. 28
·期 8
·3395
·
IF 4.6
Yi Ou,Zonglin You,Min Yao,Yingfan Cao,Xiu Xue,Min Chen,Rihui Wu,Lishe Gan,Dongli Li,Panpan Wu,Xuetao Xu,Wingleung Wong,Vincent Kam Wai Wong,Wenfeng Liu,Jiming Ye,Jingwei Jin
Naproxen is widely used for anti-inflammatory treatment but it can lead to serious side effects. To improve the anti-inflammatory activity and safety, a novel naproxen derivative containing cinnamic acid (NDC) was synthesized and used in combination with resveratrol. The results showed that the combination of NDC and resveratrol at different ratios have a synergistic anti-inflammatory efficacy in RAW264.7 macrophage cells. It was indicated that the combination of NDC and resveratrol at a ratio of 2:1 significantly inhibited the expression of carbon monoxide (NO), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), induced nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and reactive oxygen species (ROS) without detectable side effects on cell viability. Further studies revealed that these anti-inflammatory effects were mediated by the activation of nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK) and phosphoinositide-3 kinase (PI3K)/protein kinase B (Akt) signaling pathways, respectively. Taken together, these results highlighted the synergistic NDC and resveratrol anti-inflammatory activity that could be further explored as a strategy for the treatment of inflammatory disease with an improved safety profile.Keywords:naproxen derivative;resveratrol;synergistic;anti-inflammatory;mechanism
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ACTA BIOCHIMICA ET BIOPHYSICA SINICA
·
2018
·Vol. 50
·期 6
·567-578
·
IF 2.224
Zhang Yingying,Cong Linhai,He Jiayan,Wang Yu,Zou Yingying,Yang Zhihong,Hu Yuexin,Zhang Shiwen,He Xiaoguang
Hypopharyngeal carcinoma (HC) is one of the most malignant tumors in the upper aerodigestive tract. Currently, there are no effective treatments for HC. Gold nanoparticles (AuNPs) are a promising tool that can be used for plasmonic photothermal therapy (PPTT), which refers to the use of electromagnetic radiation, most often in near infrared (NIR) region, for the treatment of various medical conditions including cancer. AuNPs have been proved to be a promising tool for NIR spectroscopy-mediated photothermal therapies. In this study, we chemically conjugated AuNPs with a monoclonal antibody (mAb) targeting the epidermal growth factor receptor (EGFR), a cell-surface receptor that is overexpressed in many cancers. We then assessed the effect of NIR photothermal treatment with the EGFRmAb–AuNPs in FaDu HC cells. Our data showed that nanoparticle conjugation with the EGFRmAb improved the specific targeting towards FaDu cells and reduced cytotoxicity towards normal (293 T) cells which do not overexpress the EGFR. A significant amount of our EGFRmAb-conjugated AuNPs could enter the nucleus. Moreover, the expression levels of double strand DNA break repair proteins, including p-ATR, p-CHK1, and p-CHK2 were increased following AuNPs treatment, indicating the presence of DNA damage. These findings suggest that the AuNPs can potentially disrupt genome integrity and induce apoptosis. In addition, EGFRmAb–AuNPs+NIR could induce FaDu cell apoptosis, accompanied by the inhibition of the PI3K/AKT/mTOR pathway and stimulation of DNA damage response. Based on these data, PPTT using the EGFRmAb–AuNPs could be a new promising treatment for HC.
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