Pik3ip1通过抑制PI3K/AKT/mTOR信号通路促进牛MDSCs分化

PI3K相互作用蛋白1(Pik3ip1)为PI3K/AKT/mTOR信号通路负调控因子,其对牛MDSCs(Muscle derived satellite cells,MDSCs)分化研究较少。采用Western blot及免疫荧光,在牛MDSCs分化过程中检测Pik3ip1表达。构建Pik3ip1基因过表达及抑制载体,研究Pik3ip1对牛MDSCs分化及PI3K/AKT/mTOR信号通路活性的影响。结果表明,在牛MDSCs分化中Pik3ip1表达量逐渐升高;激活Pik3ip1表达后,细胞分化程度升高;抑制Pik3ip1表达则出现相反现象。Co-IP结果表明,在牛MDSCs分化过程中Pik3ip1与p110α相互作用。激活Pik3ip1抑制PI3K/AKT/mTOR信号通路活性。相反在抑制Pik3ip1表达后,PI3K/AKT/mTOR信号通路活性增强。综上所述,Pik3ip1通过抑制PI3K/AKT/mTOR信号通路促进牛MDSCs分化。

Mechanism of stilbene glycosides on apoptosis of SH-SY5Y cells via regulating PI3K/AKT signaling pathway

Objective:To investigate the effects of stilbene glycoside(TSG)on okadaic acid-induced apoptosis in human neuroblastoma cells(SH-SY5Y)via the PI3K/AKT pathway.Methods:The optimal concentration of OA was screened by CCK-8 assay,and SH-SY5Y cells were divided into control group,model group,TSG group,LY294002 group and LY294002+TSG group.The proliferation and apoptosis in each group were detected by CCK-8 and TUNEL assays;Western blotting method and real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of PI3K,P-PI3K(Y607),AKT,P-AKT(Ser473),Bcl-2 and Bax proteins.The relative protein expression was represented by P-PI3K(Y607)/PI3K,P-AKT(Ser473)/AKT and Bcl-2/Bax gray ratio.Results:CCK-8 screened the optimal concentration of OA as 40 nmol/L.Compared with the control group,the model group increased relative cell viability,decreased apoptosis rate,the pathway and apoptotic proteins expression levels of P-PI3K(Y607)/PI3K,P-AKT(Ser473)/AKT and Bcl-2/Bax were decreased,and the mRNA expression levels of PI3K,AKT and Bcl-2 were decreased.Bax mRNA expression level increased(P<0.05);Compared with model group,TSG group increased relative cell viability,decreased apoptosis rate,increased protein expression levels of P-PI3K(Y607)/PI3K,P-AKT(Ser473)/AKT,Bcl-2/Bax,and increased mRNA expression levels of PI3K,AKT,and Bcl-2.Bax mRNA expression decreased(P<0.05),LY294002 group decreased relative cell viability,increased apoptosis rate,P-PI3K(Y607)/PI3K protein expression levels were significantly decreased(P<0.05),P-AKT(Ser473)/AKT and Bcl-2/Bax protein expression levels were significantly decreased,but there was no statistical significance,PI3K,AKT and Bcl-2 mRNA expression levels were decreased,and Bax mRNA expression levels were increased(all P<0.05);Compared with LY294002 group,LY294002+TSG group increased relative cell viability,decreased apoptosis rate,and the protein expression levels of P-PI3K(Y607)/PI3K,P-AKT(Ser473)/AKT and Bcl-2/Bax were increased.The mRNA expression levels of PI3K,AKT,Bcl-2 were increased,Bax was decreased(all P<0.05).Conclusion:Stilbene glycoside may alleviate okadaic acid-induced apoptosis in SH-SY5Y cells by interfering with the PI3K/AKT signaling pathway,which in turn regulates the expression of apoptotic factors such as Bcl-2 and Bax.

Inositol 1,4,5-trisphosphate 3-kinases:functions and regulations

Inositol 1,4,5-trisphosphate 3-kinase (IP3 3-kinase/IP3K) plays an important role in signal transduction in animal cellsby phosphorylating inositol 1,4,5-trisphosphate (IP3) to inositol 1,3,4,5-tetrakisphosphate (IP4). Both IP3 and IP4 arecritical second messengers which regulate calcium (Ca2+) homeostasis. Mammalian IP3Ks are involved in many biologicalprocesses, including brain development, memory, learning and so on. It is widely reported that Ca2+ is a canonicalsecond messenger in higher plants. Therefore, plant IP3K should also play a crucial role in plant development. Recently,we reported the identification of plant IP3K gene (AtIpk2β/AtIP3K) from Arabidopsis thaliana and its characterization.Here, we summarize the molecular cloning, biochemical properties and biological functions of IP3Ks from animal, yeastand plant. This review also discusses potential functions of IP3Ks in signaling crosstalk, inositol phosphate metabolism,gene transcriptional control and so on.

Promoting axon regeneration in the central nervous system by increasing PI3-kinase signaling

Much research has focused on the PI3-kinase and PTEN signaling pathway with the aim to stimulate repair of the injured central nervous system.Axons in the central nervous system fail to regenerate,meaning that injuries or diseases that cause loss of axonal connectivity have life-changing consequences.In 2008,genetic deletion of PTEN was identified as a means of stimulating robust regeneration in the optic nerve.PTEN is a phosphatase that opposes the actions of PI3-kinase,a family of enzymes that function to generate the membrane phospholipid PIP_(3) from PIP_(2)(phosphatidylinositol(3,4,5)-trisphosphate from phosphatidylinositol(4,5)-bisphosphate).Deletion of PTEN therefore allows elevated signaling downstream of PI3-kinase,and was initially demonstrated to promote axon regeneration by signaling through mTOR.More recently,additional mechanisms have been identified that contribute to the neuron-intrinsic control of regenerative ability.This review describes neuronal signaling pathways downstream of PI3-kinase and PIP3,and considers them in relation to both developmental and regenerative axon growth.We briefly discuss the key neuron-intrinsic mechanisms that govern regenerative ability,and describe how these are affected by signaling through PI3-kinase.We highlight the recent finding of a developmental decline in the generation of PIP_(3) as a key reason for regenerative failure,and summarize the studies that target an increase in signaling downstream of PI3-kinase to facilitate regeneration in the adult central nervous system.Finally,we discuss obstacles that remain to be overcome in order to generate a robust strategy for repairing the injured central nervous system through manipulation of PI3-kinase signaling.

Insensitivity of PI3K/Akt/GSK3 signaling in peripheral blood mononuclear cells of age-related macular degeneration patients

Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C（IL-17RC）,a phenomenon observed in peripheral blood and chorioretinal tissues with age-related macular degeneration（AMD）,was associated with altered activation of phosphatidylinositide 3-kinase（PI3K）,Akt,and glycogen synthase kinase 3（GSK3）.We wondered whether or not altered PI3 K,Akt,and GSK3 activities could be detected in peripheral blood mononuclear cells（PBMC） obtained from AMD patients.In the patients＇ PBMC,absent or reduced serine-phosphorylation of GSK3α or GSK3β was observed,which was accompanied with increased phosphorylation of GSK3 substrates（e.g.CCAAT enhancer binding protein a,insulin receptor substrate 1,and TAU）,indicative of enhanced GSK3 activation.In addition,decreased protein mass of PI3K85α and tyrosinephosphorylation of PI3K50α was present in PBMC of the AMD patients,suggesting impaired PI3 K activation.Moreover,abnormally lowered molecular weight forms of Akt and GSK3 were detected in PBMC of the AMD patients.These data demonstrate that despite the presence of high levels of IL-17 RC,Wnt-3a and vascular endothelial growth factor,the PI3K/Akt/GSK3 signaling pathway is insensitive to these stimuli in PBMC of the AMD patients.Thus,measurement of PI3K/Akt/GSK3 expression and activity in PBMC may serve as a surrogate biomarker for AMD.

Effect on Proliferation and Erythroid Differentiation of K562 Cells by IER3IP1-Knockdown

Objective： To investigate the effect on erythroid differentiation and proliferation of K562 cells by IER3IP1-knockdown with RNA interference targeting at IER3IP1 gene. Methods： The shRNA eukaryotic expression vectors targeting at IER3IP1 gene were designed and constructed. Inhibitory effect was detected by semiquantitative RT-PCR. The impacts on K562 cells by RNAi were studied by MTT assay, benzidine staining, light microscope and electron microscopy observation, cell cycles analysis, colony formation assay and RT-PCR. The expressions of erythroid differentiation correlated genes Gfi-lB, GPA and 7-globin were studied after being exposed to 0.2μmol/L imatinib for two days. Results： The shRNA eukaryotic expression vectors were successfully constructed. The expression of IER3IP1 gene was significantly inhibited with an inhibition efficiency of 76% （P〈0.01）. Compared with the control groups, bcr/abl mRNA level was increased in K562/shRNA-IER3IP1 group （P〈0.01）. The proliferation ability was enhanced （P〈0.01） and the proportion of cells at G0/G1 phase decreased but S phase increased （P〈0.05） in K562/shRNA-IER3IP1 group. Under electron microscopy, the amount of euchromatin increased but heterochromatin decreased. There were structural abnomalities in endocytoplasmic reticulum and clusters of vesicular. The percentage of benzidine staining positive cells and mRNA expression levels of Gfi-1B, GPA and γ-globin were all decreased after being exposed to 0.2 μmol/L STI571 for two days in K562/shRNA-IER3IP1 group （P〈0.01）. Conclusion： IER3IP1-knockdown can hinder the erythroid differentiation and elevate the proliferation level of K562 cells. IER3IP1 may play a role in erythroid differentiation and proliferation of K562 cells.

Synergistic suppression of the PI3K inhibitor CAL-101 with bortezomib on mantle cell lymphoma growth

Objective: To investigate the effects of CAL-101, particularly when combined with bortezomib(BTZ) on mantle cell lymphoma(MCL) cells, and to explore its relative mechanisms.Methods: MTT assay was applied to detect the inhibitory effects of different concentrations of CAL-101. MCL cells were divided into four groups: control group, CAL-101 group, BTZ group, and CAL-101/BTZ group. The expression of PI3K-p110σ, AKT, ERK, p-AKT and p-ERK were detected by Western blot. The apoptosis rates of CAL-101 group, BTZ group, and combination group were detected by flow cytometry. The location changes of nuclear factor kappa-B(NF-κB) of 4 groups was investigated by NF-κB Kit exploring. Western blot was applied to detect the levels of caspase-3 and the phosphorylation of AKT in different groups. Results: CAL-101 dose- and time-dependently induced reduction in MCL cell viability. CAL-101 combined with BTZ enhanced the reduction in cell viability and apoptosis. Western blot analysis showed that CAL-101 significantly blocked the PI3K/AKT and ERK signaling pathway in MCL cells. The combination therapy contributed to the inactivation of NF-κB and AKT in MCL cell lines. However, cleaved caspase-3 was up-regulated after combined treatment. Conclusion: Our study showed that PI3K/p110σ is a novel therapeutic target in MCL, and the underlying mechanism could be the blocking of the PI3K/AKT and ERK signaling pathways. These findings provided a basis for clinical evaluation of CAL-101 and a rationale for its application in combination therapy, particularly with BTZ.

Liposomalα-cyperone targeting bone resorption surfaces suppresses osteoclast differentiation and osteoporosis progression via the PI3K/Akt axis

Osteoporosis is a metabolic dysregulation of bone that occurs mainly in postmenopausal women,and the hyperfunction of osteoclasts is the primary contributor to postmenopausal osteoporosis.However,the development of effective therapeutic drugs and precise delivery systems remains a challenge in the field of anti-absorption therapy.Here,we reported theα-cyperone(α-CYP)for anti-osteoporosis and developed a liposome-based nano-drug delivery system ofα-CYP,that specifically targets the bone resorption interface.Firstly,we found that theα-CYP,one of the major sesquiterpenes of Cyperus rotundus L.,attenuated the progression of osteoporosis in ovariectomized(OVX)mice and down-regulated the expression of phosphorylated proteins of phosphoinositide 3-kinase(PI3K)and protein kinase B(Akt),causing down-regulation of osteoclast-related genes/proteins and curbing osteoclast differentiation.Furthermore,α-CYP reversed the activation of osteoclastic differentiation and enhanced osteoporosis-related proteins expression caused by PI3K/Akt agonist(YS-49).More importantly,we adopted the osteoclastic resorption surface targeting peptide Asp8 and constructed the liposome(lipαC@Asp8)to deliverα-CYP to osteoclasts and confirmed its anti-osteoporosis effect and enhanced osteoclast inhibition by blocking PI3K/Akt axis.In conclusion,this study demonstrated thatα-CYP inhibits osteoclast differentiation and osteoporosis development by silencing PI3K/Akt pathway,and the liposome targeting delivery systems loaded withα-CYP might provide a novel and effective strategy to treat osteoporosis.

Regulatory Effects of Zuogui Pill on Apoptosis of Follicles in Rats Injured by 60Co-γRays Based on PI3K/Akt/m TOR Signaling Pathway

[Objectives]To explore the protective effects of Zuogui Pill on ^(60)Co-γ-ray-induced premature aging of rats based on phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)signaling pathway.[Methods]Sixty sexually mature female SD rats were irradiated with ^(60)Co-γ-ray(6.0 Gy,LD 40)for 24 h at one time.These rats were randomly divided into model group,Progynova group[0.18(g·kg)/d],Progynova[0.09(g·kg)/d]+Zuogui Pill high dose[23.625(g·kg)/d)]group,Zuogui Pill high dose[23.625(g·kg)/d)]group,Zuogui Pill medium dose[9.45(g·kg)/d)]group and Zuogui Pill low dose[4.725(g·kg)/d]group.The administration(once a day)lasted 21 d.The rat serum[follicle-stimulating hormone(FSH),luteinizing hormone(LH)and estradiol(E_(2))]were detected by Enzyme-linked immunosorbent assay(ELISA).The morphological changes of ovary were observed by hematoxylin-eosin(HE)staining.The apoptosis rate of granulosa cells was detected by terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL).The protein expression of phosphorylated(p)-PI3K,p-Akt,p-mTOR,B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax)in ovarian tissues were detected by Western blot.[Results]Compared with the normal group,the model group showed significant increase in the serum FSH(P<0.01),significant decrease in serum E_(2)(P<0.05),and decrease in the number of early follicles and luteum in the ovary(P<0.01).Besides,the apoptosis rate of granulosa cells increased significantly(P<0.01);the expression of p-PI3K,p-Akt,p-mTOR and Bcl-2 in ovarian tissue decreased significantly,while the expression of Bax increased significantly(P<0.01).Compared with the model group,the number of early follicles in the ovary increased and the apoptosis rate of granulosa cells decreased after intervention in each administration group.In addition,the protein expressions of p-PI3K,p-Akt,p-mTOR and Bcl-2 increased,while the expression of Bax decreased,especially in Progynova+Zuogui Pill high dose group,the differences were statistically significant(P<0.05,P<0.01).[Conclusions]Zuogui Pill may protect the radiation-injured ovary through activating the expression of PI3K/Akt/mTOR protein in ovarian tissue,increasing the amount of Bcl-2 protein and inhibiting the expression of Bax protein.

8K超高清AVS3编码压缩平台的设计与实现

8K超高清AVS3编码压缩平台是中央广播电视总台8K超高清频道进网入户和在“百城千屏”公共大屏落地播出的重要支撑系统之一。本文主要介绍了该平台的设计与实现,并基于该平台的建设情况进行了关键技术应用和创新的总结与探讨。

Tongxinluo Activates PI3K/AKT Signaling Pathway to Inhibit Endothelial Mesenchymal Transition and Attenuate Myocardial Fibrosis after Ischemia-Reperfusion in Mice

Objective To investigate the potential role of Tongxinluo(TXL)in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury(MIRI)in mice.Methods A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 min.According to a random number table,66 mice were randomly divided into 6 groups(n=11 per group):the sham group,the model group,the LY-294002 group,the TXL group,the TXL+LY-294002 group and the benazepril(BNPL)group.The day after modeling,TXL and BNPL were administered by gavage.Intraperitoneal injection of LY-294002 was performed twice a week for 4 consecutive weeks.Echocardiography was used to measure cardiac function in mice.Masson staining was used to evaluate the degree of myocardial fibrosis in mice.Qualitative and quantitative analysis of endothelial mesenchymal transition(EndMT)after MIRI was performed by immunohistochemistry,immunofluorescence staining and flow cytometry,respectively.The protein expressions of platelet endothelial cell adhesion molecule-1(CD31),α-smoth muscle actin(α-SMA),phosphatidylinositol-3-kinase(PI3K)and phospho protein kinase B(p-AKT)were assessed using Western blot.Results TXL improved cardiac function in MIRI mice,reduced the degree of myocardial fibrosis,increased the expression of CD31 and inhibited the expression ofα-SMA,thus inhibited the occurrence of EndMT(P<0.05 or P<0.01).TXL significantly increased the protein expressions of PI3K and p-AKT(P<0.05 or P<0.01).There was no significant difference between TXL and BNPL group(P>0.05).In addition,the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention,eliminated the protective effect of TXL,further supporting the protective effect of TXL.Conclusion TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice.

8K超高清视频分发技术的研究与实践

8K超高清视频通过高分辨率、高帧率、高色深、宽色域、高动态范围五个维度技术,为观众带来更具感染力和沉浸感的临场收视体验。本文就8K超高清视频分发技术进行了论述,重点对8K超高清视频的卫星传输、地面无线广播传输、有线传输以及互联网传输等不同传播方式进行了分析与探讨,笔者认为不同技术系统可充分发挥自身的优势与特点,为广大用户提供更加优质的8K超高清视音频体验。

Class I phosphatidylinositol 3-kinase inhibitors for cancer therapy

The phosphatidylinositol 3-kinase(PI3K) pathway is frequently activated in human cancers.Class I PI3 Ks are lipid kinases that phosphorylate phosphatidylinositol 4,5-bisphosphate(PIP2) at the 3-OH of the inositol ring to generate phosphatidylinositol 3,4,5-trisphosphate(PIP3), which in turn activates Akt and the downstream effectors like mammalian target of rapamycin(m TOR) to play key roles in carcinogenesis. Therefore, PI3 K has become an important anticancer drug target, and currently there is very high interest in the pharmaceutical development of PI3 K inhibitors. Idelalisib has been approved in USA and Europe as the first-in-class PI3 K inhibitor for cancer therapy. Dozens of other PI3 K inhibitors including BKM120 and ZSTK474 are being evaluated in clinical trials. Multifaceted studies on these PI3 K inhibitors are being performed, such as single and combinational efficacy, resistance, biomarkers,etc. This review provides an introduction to PI3 K and summarizes key advances in the development of PI3 K inhibitors.

Effects of phosphatidylinositol 3-kinase inhibitor on humancervical carcinoma cells in vitro

Phosphatidylinositol 3-kinase(PI3K)is a crucial cell survival pathway implicated in tumorigenesis because of its role in stimulating cell proliferation and suppressing apoptosis.This study was to investigate the regulation of proliferation and apoptosis by LY294002,an inhibitor of PI3K in cervical cancer cells and the expression of FLICE-like inhibitory protein(c-FLIP)in vitro.Human cervical cancer HeLa cells were used in this experiment and cultured.The cultured cells were treated with LY294002 at different concentrations(10,25,50 and 100µmol/L)for 6,12,24,and 48 h before harvesting for evaluation.Cell viability was measured by 3-(4,5)-dimethylthiazol(-2-y1)-3,5-di-phenyltetrazoliumbromide(MTT)assay.Apoptosis was analyzed byflow cytometry.The expression of c-FLIP was detected by Western blot.Cell viability was inhibited by LY294002 significantly(P<0.05).Flow cytometry analysis revealed that cell apoptosis was significantly increased in the presence of LY294002 as compared with the control group.Although the expression of c-FLIP was increased in a short time,the expression of c-FLIP was markedly suppressed after the treatment of LY294002 for 48 h.These results suggested that the PI3K/Akt signal pathway might be involved in the regulation of cell apoptosis in cervical cancer cells.Moreover,the regulation of c-FLIP expression through PI3K/Akt signal pathway in cervical cancer cells was observed in vitro.

苦参碱处理的K562细胞中IER3IP1基因表达及其对细胞增殖的影响

目的研究苦参碱诱导 K562细胞分化过程中 IER3IP1基因的表达,以明确 IER3IP1基因表达与苦参碱作用的量效及时效关系,并初步探讨该基因在 K562细胞中的功能。方法锥虫蓝染色分析苦参碱对 K562细胞的生长抑制作用;用 RT-PCR 半定量方法观察 K562细胞在不同时间、不同剂量苦参碱作用下 IER3IP1基因的表达情况;对 IER3IP1基因重组质粒转染的 K562细胞(K562/eYFP-IER3IP1)作细胞形态学及细胞增殖变化的观察,同时进行细胞周期检测以及超微结构观察。结果苦参碱对 K562细胞有增殖抑制作用,在苦参碱作用3 h 后 IER3IP1基因表达可升高3～4倍,并呈剂量依赖性,其后6～48 h 表达下降,低于非苦参碱处理组。K562/eYFP-IER3IP1细胞的增殖速度显著减缓,G_0/G_1期细胞数升高(P<0.05);且苦参碱作用24 h 后在光镜和电镜下均可见红系分化细胞增多。结论苦参碱抑制 K562细胞生长,同时使 IER3IP1基因表达以剂量依赖的方式瞬时升高,转染了 IER3IP1基因的 K562细胞对苦参碱敏感性增高,提示该基因可能参与了苦参碱作用于 K562细胞的早期反应,并在后续的红系分化中发挥作用。

钙调蛋白在C型Niemann-Pick病小鼠Purkinje细胞的表达

目的:探讨钙调蛋白在C型Niemann-Pick病(NPC)小鼠Purkinje细胞的表达。方法:采用免疫组织化学和Westen Blot技术检测3种钙调蛋白Calbindin D28k、IP3R1、SERCA2b在4、6、8周龄NPC小鼠小脑部的表达,以同周龄WT(野生型)小鼠作为对照组。结果:CalbindinD28k和IP3R1在6、8周龄时表达较WT小鼠显著下降,在4周龄时无明显减少,SERCA2b在8周龄时表达较WT小鼠显著下降。结论:3种钙调蛋白表达的下降可能导致钙失衡,参与神经元变性。

shRNA干扰IER3IP1基因表达对K562细胞增殖和红系分化的影响

目的探讨靶向干扰IER3IP1基因对K562细胞增殖和红系分化的影响。方法针对IER3IP1基因设计并构建小发夹状（shRNA）真核表达载体，转染K562细胞后用RT—PCR方法鉴定沉默效果。采用MTT实验、联苯胺染色、光镜和电镜观察、流式细胞术以及RT—PCR，观察抑制IER3IP1基因表达后对1（562细胞的影响；采用0．2μmol／L伊马替尼诱导K562细胞2d，观察诱导分化过程中IER3IP1基因表达变化情况，抑制IER3IPl基因表达后对红系分化相关基因Gfi—1B、GPA和γ—globin以及细胞表面GPA蛋白表达的影响。结果成功构建针对IER3IP1基因的shRNA真核表达载体，转染至K562细胞中，该基因mRNA表达水平明显降低，抑制率达76％（P〈0．01）。与对照组细胞相比，K562-shRNA—IER3IP1组bcr—ablmRNA表达升高（P〈0．05）；MTT检测结果显示细胞增殖能力增强（P〈0．01）；流式细胞术检测结果显示S期细胞比例增加，G0／G1期细胞比例减少（P〈0．05）；电镜可见细胞常染色质增加、异染色质减少，内质网部分扩张，囊泡样结构滞留。0．2μmol／L伊马替尼作用48h后，K562-shRNA—IER3IP1组联苯胺染色阳性率由作用前的（44．7±2．5）％降低至（22．7±1．5）％（P〈0．01），且红系分化相关基因Gfi-1B、GPA和γ—globin的mRNA表达水平明显降低，细胞表面GPA蛋白表达水平降低。同时伊马替尼作用过程中IER3IP1基因在作用3h时表达明显升高，6h时降低，12～48h表达水平基本不变。结论干扰IER3IP1基因表达后，K562细胞增殖加快，红系分化过程受阻，提示该基因可能在K562细胞增殖和向红系分化过程中发挥作用。

Fructus Zanthoxyli extract improves glycolipid metabolism disorder of type 2 diabetes mellitus via activation of AMPK/PI3K/Akt pathway:Network pharmacology and experimental validation

Objective:This study investigated the potential mechanisms behind the beneficial effects of Fructus Zanthoxyli(FZ)against type 2 diabetes mellitus(T2DM)based on network pharmacology and experimental validation.Methods:Ultra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry,and gas chromatography-mass spectrometry were used to identify the constituents of FZ.Next,the differentially expressed genes linked to the treatment of diabetes with FZ were screened using online databases(including Gene Expression Omnibus database and Swiss Target Prediction online database),and the overlapping genes and their enrichment were analyzed by Kyoto Encyclopedia of Genes and Genomes(KEGG).Finally,the pathway was verified by in vitro experiments,and cell staining with oil red and Nile red showed that the extract of FZ had a therapeutic effect on T2DM.Results:A total of 43 components were identified from FZ,and 39 differentially expressed overlapping genes were screened as the possible targets of FZ in T2DM.The dug component-target network indicated that PPARA,PPARG,PIK3R3,JAK2 and GPR88 might be the core genes targeted by FZ in the treatment of T2DM.Interestingly,the enrichment analysis of KEGG showed that effects of FZ against T2DM were closely correlated with the adenosine monophosphate-activated protein kinase(AMPK)and phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt)signaling pathways.In vitro experiments further confirmed that FZ significantly inhibited palmitic acid-induced lipid formation in Hep G2 cells.Moreover,FZ treatment was able to promote the AMPK and PI3K/Akt expressions in Hep G2 cells.Conclusion:Network pharmacology combined with experimental validation revealed that FZ extract can improve the glycolipid metabolism disorder of T2DM via activation of the AMPK/PI3K/Akt pathway.

云南台4K超高清演播室系统设计

云南广播电视台已经对4K超高清电视的制作系统进行了一些有益的探索,本文对系统的整体情况、建设要求、结构功能进行了简要介绍。

压缩与非压缩——8K电视制作构架的思考

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