REPRODUCTION FERTILITY AND DEVELOPMENT
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2023
·Vol. 35
·期 14
·669-675
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IF 1.9
Min Liu,Yong-Jie Mi,Juan Dai
Context Aquaporin 7 (AQP7) is selectively expressed in decidualised endometrial stromal cells (ESCs) of mice surrounding the embryonic implantation sites. However, the roles of AQP7 and the underlying mechanism that regulates AQP7 expression in endometrial decidualisation after implantation are still unclear.Aims This study aimed to investigate the role of the PI3K-Akt pathway in regulating the expression of AQP7 in ESCs and decidualisation.Methods Primary ESCs of pregnant mice were isolated to establish in vitro decidualisation models. PI3K inhibitor LY294002 was added to the decidualisation models, then AQP7 expression, changes in decidualised ESC morphology and expression of decidualisation marker molecules were examined.Key results AQP7 knockdown reduced the proliferation and differentiation of ESCs with in vitro induced decidualisation. Furthermore, when the activity of PI3K was inhibited by LY294002, the expression of AQP7 in decidualised ESCs was decreased and both the proliferation and differentiation of ESCs were significantly reduced.Conclusions This indicates that AQP7 is a key molecule involved in endometrial decidualisation and the expression of AQP7 is upregulated through activation of the PI3K-Akt pathways, which promotes the proliferation and differentiation of the ESCs, thus affecting occurrence of decidualisation.Implications This study may provide a new biomarker for the diagnosis of infertility and a new drug target for the prevention and treatment of infertility.
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Oncology Letters
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2018
·Vol. 15
·期 4
·5739-5743
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IF 1.664
Hua Zhang,Yumei Cao,Yuru Chen,Guangxi Li,Hanshu Yu
The present study investigated the inhibitory effects of apatinib on the proliferation of the SMMC-7721 hepatocellular carcinoma cell line to explore the possible mechanism. The MTT assay was used to detect the inhibitory effects of the different concentrations of apatinib on the proliferation of SMMC-7721 cells. Annexin V/PI double staining was performed to investigate the effects of apatinib on the apoptosis of SMMC‑7721 cells. Expression of the apoptosis-related genes Bcl-2, Bax and caspase-9 after apatinib treatment was detected by reverse transcription‑quantitative PCR (RT-qPCR) and western blot analysis. Expression of the PI3K, p-PI3K, Akt and p-Akt proteins after apatinib treatment was detected using western blot analysis. The MTT results showed that apatinib inhibited the in vitro proliferation of SMMC-7721 cells. Annexin V/PI double staining showed that apatinib induced the apoptosis of SMMC‑7721 cells in a concentration-dependent manner. Results of RT-qPCR and western blot analysis showed that apatinib was able to induce the expression of pro-apoptotic genes Bax and caspase-9 and inhibited the expression of anti-apoptotic gene Bcl-2. In addition, the western blot analysis revealed that p-PI3K and p-Akt was significantly decreased following apatinib treatment, while no significant differences were found in the total protein levels of PI3K and Akt. The results of the present show that apatinib is capable of promoting the apoptosis of SMMC-7721 cells by inhibiting the PI3K/Akt signal transduction pathway, upregulating the expression of pro-apoptotic genes Bax and caspase-9, and downregulating the expression level of the anti-apoptotic gene Bcl-2.
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BMC Complementary Medicine and Therapies
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2022
·Vol. 22
·期 1
·1-10
·
IF 2.838
Deng Jiuhong,Zheng Chao,Hua Zhou,Ci Haideng,Wang Guiying,Chen Lijing
Background Diosmin has been reported to treat diabetes, but its role in diabetic nephropathy (DN) remains unclear. This research investigated the mechanism by which diosmin alleviated high glucose (HG)-induced HK-2 cell injury.Methods First, we used CCK-8 to detect the effect of 0.1, 1, or 10 μg/mL diosmin on the viability of HK-2 cells treated with normal glucose or HG. Next, we used flow cytometry, automatic biochemical analyzer, ELISA, immunofluorescence, and colorimetric assay kit to examine the apoptosis, oxidative stress, inflammatory factors, and Caspase-3 expression in HK-2 cells. Thereafter, we used the western blot and qRT-PCR to examine the expression of the endoplasmic reticulum stress-, oxidative stress-, inflammation-, apoptosis-, and autophagy, and PI3K/AKT pathway-related factors.Results Diosmin was non-cytotoxic to normal HK-2 cells and enhanced the HK-2 cell viability suppressed by HG. Meanwhile, diosmin restrained apoptosis, the contents of MDA, pro-inflammatory factors, and Caspase-3 but intensified the contents of SOD and CAT induced by HG. We further confirmed that diosmin blunted oxidative stress-, inflammation-, apoptosis-, and autophagy-related factors expression induced by HG via restraining the CHOP and GRP78 expressions. Further, we also discovered that PTEN level was restrained and the ratios of p-PI3K/PI3K and p-AKT/AKT were enhanced in HK-2 cells induced by HG, which was reversed by co-treatment of HG and diosmin.Conclusion sOur study manifested that diosmin alleviated the HG-mediated endoplasmic reticulum stress injury in HK-2 cells via restraining the PI3K/AKT pathway.
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RENAL FAILURE
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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.
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Orthopaedic Surgery
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2022
·Vol. 14
·期 10
·2669-2681
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IF 2.279
Bo-yong Jang,Shi-bing Guo,Rui Bai,Wan-lin Liu,Yu-lin Gong,Zhen-qun Zhao
Objective To study the relationship between vascular endothelial cells (VEC) and autophagy, and its regulatory mechanism in steroid-induced avascular necrosis of the femoral head (SANFH). Methods In cell experiment, VEC were isolated and cultured from the femoral head of Sprague–Dawley rats and divided into three groups: blank control group (Ctrl), methylprednisolone group (MP), and methylprednisolone+mTOR-shRNA group (MP + shmTOR). The autophagy formation was observed by transmission electron microscope. The mRNA expression of PI3K, Akt, mTOR, Beclin1 and MAP1LC3 was detected by RT-PCR and the protein expression was detected by Western blot and immunofluorescence. Expression of the damage marker 6-keto-PGF1α was detected by the ELISA method. In vivo experiment, after establishing the model, the grouping method was the same as cell experiment. Autophagosomes were observed by same method, and the expression of related factors was detected by the same method in cell experiment. Results In the cell experiment, autophagosomes in the MP group were significantly lower than in the Ctrl group, and the autophagosomes in the MP + shmTOR group were intermediate between two groups ( P < 0.05). The mRNA expression levels of PI3K, Akt and mTOR in the MP group were significantly higher than in the Ctrl group, while the MP+ shmTOR group presented intermediate levels between these groups (average gray value were 3837.90, 2996.30, 3005.60, F = 428.64, P < 0.05). MRNA expression levels of Beclin1 and MAP1LC3 in the MP group were significantly lower than that in Ctrl group ( P < 0.05). The content of 6-keto-PGF1α in the MP + shmTOR group was higher than in the Ctrl group and lower than in the MP group at the evaluated time intervals (average absorbance value were 104.98, 206.83, 145.91, F = 352.83, P < 0.01). In vivo experiment, the content of 6-Keto-PGF1α in the hormone group increased as time went on; the mTOR-si group was higher than that in control group, but lower than that in the hormone group ( P < 0.01). The mRNA expressions of Beclin1 and MAP1LC3 in the control group were higher than those in the hormone group, while the mRNA expressions of PI3K, Akt and mTOR were lower than those in the mTOR-si group ( P < 0.05). Conclusion The steroid inhibited the physiological protective effect of autophagy on SANFH by increasing the expression of PI3K/Akt/mTOR signaling pathway related factors and decreasing the expression of Beclin1 and MAP1LC3 in the femoral head VEC.
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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.
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Frontiers in Nutrition
·
2021
·
IF 6.576
Wei Wei,Fan Xiao-Man,Jia Shao-Hui,Zhang Xi-Ping,Zhang Zhao,Zhang Xue-Jun,Zhang Jiu-Xun,Zhang Ye-Wang
Sea cucumbers are one of many marine echinoderm animals that contain valuable nutrients and medicinal compounds. The bioactive substances in sea cucumbers make them have promising biological and pharmacological properties, including antioxidant, anti-bacterial, and anti-tumor effects. In this study, sea cucumber intestinal peptide (SCIP) is a small molecular oligopeptide (<1,000 Da) extracted from sea cucumber intestines hydrolyzed by alkaline protease. The analysis of amino acid composition showed that hydrophobic amino acids and branched-chain amino acids were rich in SCIP. Nowadays, although increasing studies have revealed the biological functions of the sea cucumber active substances, there are few studies on the function of SCIP. Furthermore, due to the anti-cancer activity being an essential characteristic of sea cucumber active substances, we also investigated the anti-cancer potential and the underlying mechanism of SCIP in vivo and in vitro. The results indicate that SCIP inhibits the growth of MCF-7 tumor cells in zebrafish and increases the apoptosis of human breast cancer MCF-7 cells. Further mechanism studies confirm that SCIP promotes the expression of apoptosis-related proteins and thus promotes the breast cancer cells (MCF-7) apoptosis via inhibition of PI3K/AKT signal transduction pathway.
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Bioengineered
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2021
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IF 3.269
Yingnan Dai,Yeping Chen,Guoqian Wei,Li Zha,Xueqi Li
Ivabradine (Iva), a heart rate reducing agent that specifically inhibits the pacemaker I(f) ionic current, has been demonstrated to be cardioprotective in many cardiovascular diseases. Autophagy is an evolutionarily conserved metabolic process that regulates cardiac homeostasis. This study is aimed to explore whether autophagy is functionally involved in the cardioprotective effect of Iva in a rat model of myocardial infarction (MI). We observed that Iva treatment (po, 10 mg/kg/day) showed significant recovery on the hemodynamics parameters in MI rats, including left ventricular systolic pressure, left ventricular end diastolic pressure, and maximal ascending/descending rate of left ventricular pressure. Also, Iva treatment dramatically decreased infarct size, inhibited myocardial apoptosis, and reduced the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in MI rats. Moreover, Iva treatment enhanced autophagy and inhibited PI3K/AKT/mTOR/p70S6K pathway in MI rats. Simultaneously, we observed that autophagy enhancer rapamycin (ip, 10 mg/kg/day) showed similar cardioprotective effects with Iva. Furthermore, we observed that addition of autophagy inhibitor 3-methyladenine (ip, 10 mg/kg/day) counteracted the therapeutic effect of Iva, addressing that Iva attenuated post-MI cardiac injury by enhancing autophagy. In summary, these findings demonstrated that Iva attenuated MI in rats by enhancing autophagy, and PI3K/AKT/mTOR/p70S6K pathway might be involved in the process. Autophagy activation by Iva may be a potential therapeutic strategy for the treatment of MI.
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International Journal of Biological Sciences
·
2021
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IF 6.582
Deng-Pan Wu,Yan Zhou,Li-Xiang Hou,Xiao-Xiao Zhu,Wen Yi,Si-Man Yang,Tian-Yu Lin,Jin-Lan Huang,Bei Zhang,Xiao-Xing Yin
Tamoxifen (TAM) resistance has indicated a significant challenge during endocrine therapy for hormone-sensitive breast cancer. Thus, it is significant to elucidate the molecular events endowing TAM resistance to endocrine therapy. In this study, we found that epithelial-mesenchymal transition (EMT) was an important event to confer TAM resistance, and attenuating EMT by elevating connexin (Cx) 43 expression could reverse TAM resistance. Specifically, Cx43 overexpression improved TAM sensitivity, while Cx43 depletion facilitated TAM insensitivity by modulating EMT in T47D TAM-resistant and -sensitive cells, and transplanted xenografts. Importantly, we found a novel reciprocal regulation between Cx43 and c-Src/PI3K/Akt pathway contributing to EMT and TAM resistance in breast cancer. Moreover, we identified that Cx43 deficiency was significantly correlated with poor relapse-free survival in patients undergoing TAM treatment. Therefore, Cx43 represents a prognostic marker and an attractive target for breast cancer treatments. Therapeutic strategies designed to increase or maintain Cx43 function may be beneficial to overcome TAM resistance.
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Bio-Design and Manufacturing
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2020
·Vol. 4
·期 1
·72-86
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IF 4.095
Xing Zheng,Zhao Chen,Zhang Chunchen,Fan Yubo,Liu Haifeng
For the surgical treatment of cardiovascular disease (CVD), there is a clear and unmet need in developing small-diameter (diameter < 6 mm) vascular grafts. In our previous work, sulfated silk fibroin (SF) was successfully fabricated as a potential candidate for preparing vascular grafts due to the great cytocompatibility and hemocompatibility. However, vascular graft with single layer is difficult to adapt to the complex internal environment. In this work, polycaprolactone (PCL) and sulfated SF were used to fabricate bilayer vascular graft (BLVG) to mimic the structure of natural blood vessels. To enhance the biological activity of BLVG, nicorandil (NIC), an FDA-approved drug with multi-bioactivity, was loaded in the BLVG to fabricate NIC-loaded BLVG. The morphology, chemical composition and mechanical properties of NIC-loaded BLVG were assessed. The results showed that the bilayer structure of NIC-loaded BLVG endowed the graft with a biphasic drug release behavior. The in vitro studies indicated that NIC-loaded BLVG could significantly increase the proliferation, migration and antioxidation capability of endothelial cells (ECs). Moreover, we found that the potential biological mechanism was the activation of PI3K/AKT/eNOS signaling pathway. Overall, the results effectively demonstrated that NIC-loaded BLVG had a promising in vitro performance as a functional small-diameter vascular graft.
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JOURNAL OF HAZARDOUS MATERIALS
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2020
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IF 9.038
Lanqiao Wang,Lanxi Wang,Xu Shi,Shiwen Xu
Excessive chlorpyrifos (CPF) in the environment causes toxicity to nontarget organisms by triggering oxidative stress. Phosphatase and tensin homolog deleted on chromosome ten (PTEN) plays an important role in controlling apoptosis and necrosis by negatively regulating the phosphatidylinositol 3-kinase/threonine kinase (PI3K/AKT) pathway. However, the effects of different concentrations of CPF on grass fish liver cell injury and the role of the ROS/PTEN/PI3K/AKT axis remain poorly understood. In this study, L8824 cells treated with different concentrations of CPF (0, 40, 60, or 80 μM) were used as the research object. The results showed that the median inhibitory concentration (IC50) was 112.226 μM. As the CPF concentrations increased, the ROS and MDA levels increased, and the T-AOC levels and SOD/GPx/GST activities decreased. As PTEN expression increased, PI3K/AKT, BCL-2, and Caspase-8 expression dramatically decreased. Conversely, RIPK1/RIPK3/MLKL and Bax/Cyt-c/Caspase-3 expression increased. Additionally, necroptosis increased in a dose-dependent manner, while apoptosis first increased and then decreased. In conclusion, our study showed that CPF could trigger oxidative stress and induce apoptosis and necroptosis in fish liver cells by regulating the ROS/PTEN/PI3K/AKT axis, and the type of damage induced was dose-dependent. These results are meaningful for toxicological studies of CPF and efforts to protect the ecosystem.
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2020
·
IF 2.985
Gen Liu,Bo-fang Zhang,Qi Hu,Xiao-pei Liu,Jing Chen
Syringic acid is an abundant phenolic acid compound that possesses anti-oxidant, anti-microbial, anti-inflammatory, and anti-endotoxic properties. However, the research of pretreatment with syringic acid against myocardial ischemia reperfusion is still limited. Thus, our research revealed the protective effect of syringic acid in the rat model with myocardial ischemia reperfusion injury. Histological analysis was performed by hematoxylin and eosin (H&E). The myocardial systolic function was detected by echocardiographic. Myocardial infarct size was measured by Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC) double staining. The apoptosis index was recorded by Terminal deoxynucleotidyl transferase dUTP nick end labeling staining (TUNEL). The contents of creatine kinase MB (CK-MB) and lactate dehydrogenase (LDH) in the serum were determined by a commercial kit. The expression of the PI3K/Akt/GSK-3β signaling pathway-related molecules and apoptosis-associated indicators was detected by western blotting or real-time PCR. We found that pretreatment with syringic acid obviously increased the myocardial systolic function (LVEF and LVFS) and decreased the infarct size, the apoptosis index as well as the serum level of CK-MB and LDH. Meanwhile, syringic acid also remarkably augmented the contents of p-PI3K, p-Akt, p-GSK-3β, Bcl-2 and mitochondria cytochrome c . However, the expression of caspase-3, -9 and Bax significantly reduced. Interestingly, co-treatment with PI3K inhibitor of LY294002 counteracted those effects induced by syringic acid. In conclusion, pretreatment with syringic acid can mitigate myocardial ischemia reperfusion injury by inhibiting mitochondria-induced apoptosis which is regulated by the PI3K/Akt/GSK-3β signaling pathway .
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