Gga-miRNA-181-5p family facilitates chicken myogenesis via targeting TGFBR1 to block TGF-βsignaling

MicroRNAs(miRNAs)have been demonstrated to control chicken skeletal muscle growth,however,the potential function of the miR-181-5p family in chicken myogenesis remains largely unknown.Here,our study identified the two chicken(Gallus gallus;Gga)miR-181-5p family members widely expressed in various tissues,specifically miR-181a-5p and miR-181b-5p.Besides,the breast muscles of fast-growing broilers expressed higher levels of miR-181a-5p and miR-181b-5p than those of slow-growing layers.Functionally,miR-181a-5p and miR-181b-5p both promote the expression level of myogenic factors including myogenin(MyoG),myogenic differentiation 1(MyoD1),and myosin heavy chain(MyHC),meanwhile accelerating the myotube formation of skeletal muscle satellite cells(SMSCs).Mechanistically,miR-181a-5p and miR-181b-5p directly bind to the 3′untranslated region(UTR)of the transforming growth factor beta receptor 1(TGFBR1)mRNA,further reducing the expression of TGFBR1.TGFBR1 is a key Transforming growth factor beta(TGF-β)signaling transduction receptor and had a negative function in muscle cell differentiation.Furthermore,knockdown of TGFBR1 facilitated the expression of chicken myogenic factors,boosted myotube formation,and decreased the SMAD family member 2/3(SMAD2/3)phosphorylation in chicken SMSCs.SMAD2/3 are downstream of TGF-βsignaling,and miR-181a-5p and miR-181b-5p could reduce the expression of TGFBR1 to further diminish the SMAD2/3 phosphorylation.Our findings revealed that the miR-181-5p family targets TGFBR1 to break the TGF-βsignaling transduction,which resulted in promoting chicken skeletal muscle development.

Inhibition of Notch 1 signaling in the subacute stage after stroke promotes striatal astrocyte-derived neurogenesis

Inhibition of Notch1 signaling has been shown to promote astrocyte-derived neurogenesis after stroke.To investigate the regulatory role of Notch1 signaling in this process,in this study,we used a rat model of stroke based on middle cerebral artery occlusion and assessed the behavior of reactive astrocytes post-stroke.We used theγ-secretase inhibitor N-[N-(3,5-diuorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester(DAPT)to block Notch1 signaling at 1,4,and 7 days after injury.Our results showed that only administration of DAPT at 4 days after stroke promoted astrocyte-derived neurogenesis,as manifested by recovery of white matter fiber bundle integrity on magnetic resonance imaging,which is consistent with recovery of neurologic function.These findings suggest that inhibition of Notch1 signaling at the subacute stage post-stroke mediates neural repair by promoting astrocyte-derived neurogenesis.

18β-glycyrrhetinic acid promotes gastric cancer cell autophagy and inhibits proliferation by regulating miR-328-3p/signal transducer and activator of transcription 3

BACKGROUND Gastric cancer(GC)is one of the most common cancer types worldwide,and its prevention and treatment methods have garnered much attention.As the active ingredient of licorice,18β-glycyrrhetinic acid(18β-GRA)has a variety of pharmacological effects.The aim of this study was to explore the effective target of 18β-GRA in the treatment of GC,in order to provide effective ideas for the clinical prevention and treatment of GC.AIM To investigate the mechanism of 18β-GRA in inhibiting cell proliferation and promoting autophagy flux in GC cells.METHODS Whole transcriptomic analyses were used to analyze and screen differentially expressed microRNAs(miRNAs)in GC cells after 18β-GRA intervention.Lentivirus-transfected GC cells and the Cell Counting Kit-8 were used to detect cell proliferation ability,cell colony formation ability was detected by the clone formation assay,and flow cytometry was used to detect the cell cycle and apoptosis.A nude mouse transplantation tumor model of GC cells was constructed to verify the effect of miR-328-3p overexpression on the tumorigenicity of GC cells.Tumor tissue morphology was observed by hematoxylin and eosin staining,and microtubule-associated protein light chain 3(LC3)expression was detected by immunohistochemistry.TransmiR,STRING,and miRWalk databases were used to predict the relationship between miR-328-3p and signal transducer and activator of transcription 3(STAT3)-related information.Expression of STAT3 mRNA and miR-328-3p was detected by quantitative polymerase chain reaction(qPCR)and the expression levels of STAT3,phosphorylated STAT3(p-STAT3),and LC3 were detected by western blot analysis.The targeted relationship between miR-328-3p and STAT3 was detected using the dual-luciferase reporter gene system.AGS cells were infected with monomeric red fluorescent protein-green fluorescent protein-LC3 adenovirus double label.LC3 was labeled and autophagy flow was observed under a confocal laser microscope.RESULTS The expression of miR-328-3p was significantly upregulated after 18β-GRA intervention in AGS cells(P=4.51E-06).Overexpression of miR-328-3p inhibited GC cell proliferation and colony formation ability,arrested the cell cycle in the G0/G1 phase,promoted cell apoptosis,and inhibited the growth of subcutaneous tumors in BALB/c nude mice(P<0.01).No obvious necrosis was observed in the tumor tissue in the negative control group(no drug intervention or lentivirus transfection)and vector group(the blank vector for lentivirus transfection),and more cells were loose and necrotic in the miR-328-3p group.Bioinformatics tools predicted that miR-328-3p has a targeting relationship with STAT3,and STAT3 was closely related to autophagy markers such as p62.After overexpressing miR-328-3p,the expression level of STAT3 mRNA was significantly decreased(P<0.01)and p-STAT3 was downregulated(P<0.05).The dual-luciferase reporter gene assay showed that the luciferase activity of miR-328-3p and STAT33’untranslated regions of the wild-type reporter vector group was significantly decreased(P<0.001).Overexpressed miR-328-3p combined with bafilomycin A1(Baf A1)was used to detect the expression of LC3 II.Compared with the vector group,the expression level of LC3 II in the overexpressed miR-328-3p group was downregulated(P<0.05),and compared with the Baf A1 group,the expression level of LC3 II in the overexpressed miR-328-3p+Baf A1 group was upregulated(P<0.01).The expression of LC3 II was detected after intervention of 18β-GRA in GC cells,and the results were consistent with the results of miR-328-3p overexpression(P<0.05).Additional studies showed that 18β-GRA promoted autophagy flow by promoting autophagosome synthesis(P<0.001).qPCR showed that the expression of STAT3 mRNA was downregulated after drug intervention(P<0.05).Western blot analysis showed that the expression levels of STAT3 and p-STAT3 were significantly downregulated after drug intervention(P<0.05).CONCLUSION 18β-GRA promotes the synthesis of autophagosomes and inhibits GC cell proliferation by regulating the miR-328-3p/STAT3 signaling pathway.

Antitumor activity of miR-188-3p in gastric cancer is achieved by targeting CBL expression and inactivating the AKT/mTOR signaling

BACKGROUND Altered miR-188-3p expression has been observed in various human cancers.AIM To investigate the miR-188-3p expression,its roles,and underlying molecular events in gastric cancer.METHODS Fifty gastric cancer and paired normal tissues were collected to analyze miR-188-3p and CBL expression.Normal and gastric cancer cells were used to manipulate miR-188-3p and CBL expression through different assays.The relationship between miR-188-3p and CBL was predicted bioinformatically and confirmed using a luciferase gene reporter assay.A Kaplan-Meier analysis was used to associate miR-188-3p or CBL expression with patient survival.A nude mouse tumor cell xenograft assay was used to confirm the in vitro data.RESULTS MiR-188-3p was found to be lower in the plasma of gastric cancer patients,tissues,and cell lines compared to their healthy counterparts.It was associated with overall survival of gastric cancer patients(P<0.001),tumor differentiation(P<0.001),lymph node metastasis(P=0.033),tumor node metastasis stage(I/II vs III/IV,P=0.024),and American Joint Committee on Cancer stage(I/II vs III/IV,P=0.03).Transfection with miR-188-3p mimics reduced tumor cell growth and invasion while inducing apoptosis and autophagy.CBL was identified as a direct target of miR-188-3p,with its expression antagonizing the effects of miR-188-3p on gastric cancer(GC)cell proliferation by inducing tumor cell apoptosis and autophagy through the inactivation of the Akt/mTOR signaling pathway.The in vivo data confirmed antitumor activity via CBL downregulation in gastric cancer.CONCLUSION The current data provides ex vivo,in vitro,and in vivo evidence that miR-188-3p acts as a tumor suppressor gene or possesses antitumor activity in GC.

Low noise,continuous-wave single-frequency 1.5-μm laser generated by a singly resonant optical parametric oscillator

We report a low noise continuous-wave （CW） single-frequency 1.5-μm laser source obtained by a singly resonant optical parametric oscillator （SRO） based on periodically poled lithium niobate （PPLN）. The SRO was pumped by a CW single-frequency Nd：YVO4 laser at 1.06μm. The 1.02 W of CW single-frequency signal laser at 1.5 μm was obtained at pump power of 6 W. At the output power of around 0.75 W, the power stability was better than ±l.5% and no mode-hopping was observed in 30 min and frequency stability was better than 8.5 MHz in 1 min. The signal wavelength could be tuned from 1.57 to 1.59 μm by varying the PPLN temperature. The 1.5-μm laser exhibits low noise characteristics, the intensity noise of the laser reaches the shot noise limit （SNL） at an analysis frequency of 4 MHz and the phase noise is less than 1 dB above the SNL at analysis frequencies above 10 MHz.

A Probable Short Decimetric Type Ⅰ-like Noise Storm: Associated with Type Ⅲ Bursts?

A rare Type I-like noise storm was observed with the solar radio spectrometers (1.0-2.0 GHz and 2.60-3.8 GHz) at National Astronomical Observatories of China (NAOC) on September 23, 1998. We concentrate on checking the Type I-like noise storm occurred in the decay phase of a Type Ⅳ radio burst. This noise storm consists of many Type I bursts and isolated Type Ⅲ or Type Ⅲ pair bursts. It has a bandwidth of ≤0.5 GHz. The duration of each Type I burst is of the order of 100-300 ms. The total duration is greater than 11 minutes. The circular polarization degree of the components of Type Ⅰ and associated Type Ⅲ bursts are about 40%-100% and almost 100%, respectively, which is greater than that of the background continuum (nearly the precision of our instrument). This short decimetric Type Ⅰ-like storm may be another kind or the extension of the kind of metric Type Ⅰ storm, and may possess the duality of metric and decimetric radio emission. It may be in favor of an earlier emission mechanism of the fundamental plasma radiation due to the coalescence of Langmuir waves with low-frequency waves.

Performance Analysis of Outage Probability and Error Rate of Square M-QAM in Mobile Wireless Communication Systems over Generalized α-μ Fading Channels with Non-Gaussian Noise

This paper derives new and exact closed-form expressions for the average symbol error rate(SER) of square M-ary quadrature amplitude modulation(M-QAM) in wireless communication systems over theα-μfading channels subject to an additive non-Gaussian noise. The obtained expressions take into account static and mobile wireless receivers. In addition, a closed-form expression for the outage probability in mobile networks is obtained. Please note that all derived expressions in this paper a valid for integer and non-integer values of the fading parameters. Analytical results are presented to study the impact of noise shaping parameter, severity of fading, and mobility on the average SER. Monte-Carlo simulations results are also provided to validate the accuracy of the analytical results.

Suppressive Influence of Time- Space White Noise on the Explosion of Solutions of Stochastic Fokker- Planck Delay Differential Equations

It is generally known that the solutions of deterministic and stochastic differential equations （SDEs） usually grow linearly at such a rate that they may become unbounded after a small lapse of time and may eventually blow up or explode in finite time. If the drift and diffusion functions are globally Lipschitz, linear growth may still be experienced, as well as a possible blow-up of solutions in finite time. In this paper, a nonlinear scalar delay differential equation with a constant time lag is perturbed by a multiplicative Ito-type time - space white noise to form a stochastic Fokker-Planck delay differential equation. It is established that no explosion is possible in the presence of any intrinsically slow time - space white noise of Ito - type as manifested in the resulting stochastic Fokker- Planck delay differential equation. Time - space white noise has a role to play since the solution of the classical nonlinear equation without it still exhibits explosion.

MiR-204-3p overexpression inhibits gastric carcinoma cell proliferation by inhibiting the MAPK pathway and RIP1/MLK1 necroptosis pathway to promote apoptosis

BACKGROUND Gastric carcinoma(GC)is the third most frequent cause of cancer-related death,highlighting the pressing need for novel clinical treatment options.In this regard,microRNAs(miRNAs)have emerged as a promising therapeutic strategy.Studies have shown that miRNAs can regulate related signaling pathways,acting as tumor suppressors or tumor promoters.AIM To explore the effect of miR-204-3p on GC cells.METHODS We measured the expression levels of miR-204-3p in GC cells using quantitative real-time polymerase chain reaction,followed by the delivery of miR-204-3p overexpression and miR-204-3p knockdown vectors into GC cells.CCK-8 was used to detect the effect of miR-204-3p on the proliferation of GC cells,and the colony formation ability of GC cells was detected by the clonal formation assay.The effects of miR-204-3p on GC cell cycle and apoptosis were detected by flow cytometry.The BABL/c nude mouse subcutaneous tumor model using MKN-45 cells was constructed to verify the effect of miR-204-3p on the tumorigenicity of GC cells.Furthermore,the study investigated the effects of miR-204-3p on various proteins related to the MAPK signaling pathway,necroptosis signaling pathway and apoptosis signaling pathway on GC cells using Western blot techniques.RESULTS Firstly,we found that the expression of miR-204-3p in GC was low.When treated with the lentivirus overexpression vector,miR-204-3p expression significantly increased,but the lentivirus knockout vector had no significant effect on miR-204-3p.In vitro experiments confirmed that miR-204-3p overexpression inhibited GC cell viability,promoted cell apoptosis,blocked the cell cycle,and inhibited colony formation ability.In vivo animal experiments confirmed that miR-204-3p overexpression inhibited subcutaneous tumorigenesis ability in BABL/c nude mice.Simultaneously,our results verified that miR-204-3p overexpression can inhibit GC cell proliferation by inhibiting protein expression levels of KRAS and p-ERK1/2 in the MAPK pathway,as well as inhibiting protein expression levels of p-RIP1 and p-MLK1 in the necroptosis pathway to promote the BCL-2/BAX/Caspase-3 apoptosis pathway.CONCLUSION MiR-204-3p overexpression inhibited GC cell proliferation by inhibiting the MAPK pathway and necroptosis pathway to promote apoptosis of GC cells.Thus,miR-204-3p may represent a new potential therapeutic target for GC.

Diurnal emission of herbivore-induced(Z)-3-hexenyl acetate and allo-ocimene activates sweet potato defense responses to sweet potato weevils

The sweet potato weevil(Cylas formicarius(Fab.)(Coleoptera: Brentidae)) is a pest that feeds on sweet potato(Ipomoea batatas(L.) Lam.(Solanales: Convolvulaceae)), causing substantial economic losses annually. However, no safe and effective methods have been found to protect sweet potato from this pest. Herbivore-induced plant volatiles(HIPVs)promote various defensive bioactivities, but their formation and the defense mechanisms in sweet potato have not been investigated. To identify the defensive HIPVs in sweet potato, the release dynamics of volatiles was monitored.The biosynthetic pathways and regulatory factors of the candidate HIPVs were revealed via stable isotope tracing and analyses at the transcriptional and metabolic levels. Finally, the anti-insect activities and the defense mechanisms of the gaseous candidates were evaluated. The production of(Z)-3-hexenyl acetate(z3HAC) and allo-ocimene was induced by sweet potato weevil feeding, with a distinct circadian rhythm. Ipomoea batatas ocimene synthase(IbOS) is first reported here as a key gene in allo-ocimene synthesis. Insect-induced wounding promoted the production of the substrate,(Z)-3-hexenol, and upregulated the expression of IbOS, which resulted in higher contents of z3HAC and allo-ocimene,respectively. Gaseous z3HAC and allo-ocimene primed nearby plants to defend themselves against sweet potato weevils. These results provide important data regarding the formation, regulation, and signal transduction mechanisms of defensive volatiles in sweet potato, with potential implications for improving sweet potato weevil management strategies.

Improved extracellular endo-1,4-β-mannosidase activity of recombinant Pichia pastoris by optimizing signal peptide

In order to improve the extracellular endo-1,4-β-mannosidase(MAN) activity of recombinant Pichia pastoris, optimization of signal peptides was investigated. At first, five potential signal peptides(W1, MF4 I, INU1 A, αpre, HFBI) were chosen to be analyzed by Signal P 4.0, among which W1 was designed. Then, the widely used signal peptide α-factor in expression vector p GAPZαA was replaced by those five signal peptides to reconstruct five new expression vectors. MAN activity was assayed after expression vectors were transformed into Pichia pastoris. The data show that the relative efficiencies of W1, MF4 I, INU1 A, αpre, and HFBI signal peptides are 23.5%, 203.5%, 0, 79.7%, and 120.3% compared with α-factor, respectively. The further gene copy number determination by the quantitative real-time PCR reveals that the MAN activities mediated by α-factor from 1 to 6 gene copy number levels are 12.95, 43.33, 126.63, 173.53, 103.23 and 88.63 U/m L, while those mediated by MF4 I are 79.22, 133.89, 260.14, 347.5, 206.15 and 181.89 U/m L, respectively. The maximum MAN activity reached 347.5 U/m L with 4 gene copies mediated by MF4 I. These results indicate that replacing the signal peptide α-factor with MF4 I and increasing MAN gene copies to a proper number can greatly improve the secretory expression of MAN.

Hepatitis C virus core protein-induced miR-93-5p upregulation inhibits interferon signaling pathway by targeting IFNAR1

AIM To investigate the mechanism by which hepatitis C virus(HCV) core protein-induced mi R-93-5 p up-regulation regulates the interferon(IFN) signaling pathway.METHODS HCV-1 b core protein was exogenously expressed in Huh7 cells using pc DNA3.1(+) vector. The expression of mi R-93-5 p and interferon receptor 1(IFNAR1) was measured using quantitative reverse transcriptionpolymerase chain reaction and Western blot. The protein expression and phosphorylation level of STAT1 were evaluated by Western blot. The overexpression and silencing of mi R-93-5 p and IFNAR1 were performed using mi R-93-5 p agomir and antagomir, and pc DNA3.1-IFNAR1 and IFNAR1 si RNA, respectively. Luciferase assay was used to identify whether IFNAR1 is a target of mi R-93-5 p. Cellular experiments were also conducted.RESULTS Serum mi R-93-5 p level was increased in patients with HCV-1 b infection and decreased to normal level after HCV-1 b clearance, but persistently increased in those with pegylated interferon-α resistance, compared with healthy subjects. Serum mi R-93-5 p expression had an AUC value of 0.8359 in distinguishing patients with pegylated interferon-α resistance from those with pegylated interferon-α sensitivity. HCV-1 b core protein increased mi R-93-5 p expression and induced inactivation of the IFN signaling pathway in Huh7 cells. Furthermore, IFNAR1 was identified as a direct target of mi R-93-5 p, and IFNAR1 restore could rescue mi R-93-5 p-reduced STAT1 phosphorylation, suggesting that the mi R-93-5 p-IFNAR1 axis regulates the IFN signaling pathway.CONCLUSION HCV-1 b core protein-induced mi R-93-5 p up-regulation inhibits the IFN signaling pathway by directly targeting IFNAR1, and the mi R-93-5 p-IFNAR1 axis regulates STAT1 phosphorylation. This axis may be a potential therapeutic target for HCV-1 b infection.

Differentially expressed genes and signalling pathways are involved in mouse osteoblast-like MC3T3-E1 cells exposed to 17-β estradiol

Oestrogen is essential for maintaining bone mass, and it has been demonstrated to induce osteoblast proliferation and bone formation.In this study, complementary DNA（cDNA） microarrays were used to identify and study the expression of novel genes that may be involved in MC3T3-E1 cells’ response to 17-b estradiol. MC3T3-E1 cells were inoculated in minimum essential media alpha（a-MEM）cell culture supplemented with 17-b estradiol at different concentrations and for different time periods. MC3T3-E1 cells treated with1028mol？L2117-b estradiol for 5 days exhibited the highest proliferation and alkaline phosphatase（ALP） activity; thus, this group was chosen for microarray analysis. The harvested RNA was used for microarray hybridisation and subsequent real-time reverse transcription polymerase chain reaction（RT-PCR） to validate the expression levels for selected genes. The microarray results were analysed using both functional and pathway analysis. In this study, microarray analysis detected 5 403 differentially expressed genes,of which 1 996 genes were upregulated and 3 407 genes were downregulated, 1 553 different functional classifications were identified by gene ontology（GO） analysis and 53 different pathways were involved based on pathway analysis. Among the differentially expressed genes, a portion not previously reported to be associated with the osteoblast response to oestrogen was identified. These findings clearly demonstrate that the expression of genes related to osteoblast proliferation, cell differentiation, collagens and transforming growth factor beta（TGF-b）-related cytokines increases, while the expression of genes related to apoptosis and osteoclast differentiation decreases, following the exposure of MC3T3-E1 cells to a-MEM supplemented with 17-b estradiol. Microarray analysis with functional gene classification is critical for a complete understanding of complementary intracellular processes. This microarray analysis provides large-scale gene expression data that require further confirmatory studies.

Geniposide, the component of the Chinese herbal formula Tongluojiunao, protects amyloid-β peptide(1–42)-mediated death of hippocampal neurons via the non-classical estrogen signaling pathway

Tongluojiunao （TLJN） is an herbal medicine consisting of two main components, geniposide and ginsenoside Rg1. TLJN has been shown to protect primary cultured hippocampal neurons. How-ever, its mechanism of action remains unclear. In the present study, primary cultured hippocampal neurons treated with Aβ1-42 （10 μmol/L） signiifcantly increased the release of lactate dehydroge-nase, which was markedly reduced by TLJN （2 μL/mL）, speciifcally by the component geniposide （26 μmol/L）, but not ginsenoside Rg1 （2.5 μmol/L）. hTe estrogen receptor inhibitor, ICI182780 （1 μmol/L）, did not block TLJN-or geniposide-mediated decrease of lactate dehydrogenase under Aβ1-42-exposed conditions. However, the phosphatidyl inositol 3-kinase or mitogen-activated protein kinase pathway inhibitor, LY294002 （50 μmol/L） or U0126 （10 μmol/L）, respectively blo cked the decrease of lactate dehydrogenase mediated by TLJN or geniposide. hTerefore, these results suggest that the non-classical estrogen pathway （i.e., phosphatidyl inositol 3-kinase or mitogen-activated protein kinase） is involved in the neuroprotective effect of TLJN, speciifcally its component, geniposide, against Aβ1-42-mediated cell death in primary cultured hippocampal neurons.

miR-146a-5p affects inflammation response of trophoblast by inhibiting TRAF6/NF-кB signaling pathway

Objective:To investigate the association of Micro-rna(miR)-146a-5p expression with preeclampsia,and further explore the potential mechanism involved.Methods:Compared with the blank control group,the expressions of miR-146a-5p and TRAF6 were detected in lipopolysaccharide(LPS)-induced JEG-3 cells.Chorionic carcinoma cell JEG-3 in vitro culture are divided into control,miR-146a-5p mimic+lipopolysaccharide(lps),miR-146a-5p mimic and miR-146a-5p inhibitor groups.qRT-PCR analysis were used to detect the mRNA of miR-146a-5p,IL-1β,IL-6,IL-8 and TNF-α.Western blot assays were carried out to determine the protein expression of TRAF6/NF-кB pathway related proteins.Results:1.miR-146a expression in miR-146a mimic group were significantly higher than the other three groups(P<0.05).2.Compared with the control group,the expression level of miR-146a-5p in JEG-3 cells induced by LPS was significantly increased,and the expression level of TRAF6 was significantly reduced(P<0.05).3.Compared with the control group,the mRNA expression levels of IL-1β,IL-6,IL-8,and TNF-αdecreased significantly after using miR-146a mimic(P<0.05).After adding miR-146a inhibitor,the mRNA expression levels of IL-1β,IL-6,IL-8,and TNF-αwere significantly increased(P<0.05).However,compared with the mimic+LPS group,the difference was not statistically significant(all P>0.05).The results of Western Blot showed that the expression of TRAF6 and NF-κB protein in JEG-3 cells decreased significantly after adding miR-146a mimic and increased after adding miR-146a inhibitor.Conclusion:MiR-146-5p can affect the inflammation response of Maternal-fetal interface by inhibiting TRAF6/NF-кB signaling pathway in preeclampsia.

Effects of (-)-Epigallocatechin gallate on some protein factors involved in the epidermal growth factor receptor signaling pathway

（-）-Epigallocatechin gallate （EGCG）, a major polyphenolic constituent of green tea, can inhibit activity of specific receptor tyrosine kinases （RTKs） and related downstream signal transduction pathways, resulting in the control of unwanted cell proliferation. The epidermal growth factor receptor （EGFR） signaling pathway is one of the most important pathways that regulates growth, survival,proliferation and differentiation in mammalian cells. This review addresses the effects of EGCG on some protein factors involved in the EGFR signaling pathway in a direct or indirect manner. Based on our understanding of the interaction between EGCG and these factors, and based on their structures, EGCG could be used as a lead compound for designing and synthesizing novel drugs with significant biological activity.

Promotion effect of FOXCUT as a microRNA sponge for miR-24-3p on progression in triple-negative breast cancer through the p38 MAPK signaling pathway

Background:Triple-negative breast cancer(TNBC)is a type of highly invasive breast cancer with a poor prognosis.According to new research,long noncoding RNAs(lncRNAs)play a significant role in the progression of cancer.Although the role of lncRNAs in breast cancer has been well reported,few studies have focused on TNBC.This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript(FOXCUT)in triple-negative breast cancer.Methods:Based on a bioinformatic analysis of the cancer genome atlas(TCGA)database,we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues,which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University.The functions of FOXCUT in proliferation,migration,and invasion were detected in vitro or in vivo.Luciferase assays and RNA immunoprecipitation(RIP)were performed to reveal that FOXCUT acted as a competitive endogenous RNA(ceRNA)for the microRNA miR-24-3p and consequently inhibited the degradation of p38.Results:lncRNA FOXCUT was markedly highly expressed in breast cancer,which was associated with poor prognosis in some cases.Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo.Mechanistically,FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38,which might act as an oncogene in breast cancer.Conclusion:Collectively,this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.

Activation of stress-response genes by retrograde signaling-mediated destabilization of nuclear importin IMPα-9 and its interactor TPR2

Stress-induced retrograde signal transmission from the plastids to the nucleus has long puzzled plant biologists.To address this,we performed a suppressor screen of the ceh1 mutant,which contains elevated 2-C-methyl-d-erythritol-2,4-cyclopyrophosphate(MEcPP)levels,and identified the gain-of-function mutant impα-9,which shows reversed dwarfism and suppressed expression of stress-response genes in the ceh1 background despite heightened MEcPP.Subsequent genetic and biochemical analyses established that the accumulation of MEcPP initiates an upsurge in Arabidopsis SKP1-like 1(ASK1)abundance,a pivotal component in the proteasome degradation pathway.This increase in ASK1 prompts the degradation of IMPα-9.Moreover,we uncovered a protein-protein interaction between IMPα-9 and TPR2,a transcriptional co-suppressor and found that a reduction in IMPα-9 levels coincides with a decrease in TPR2 abundance.Significantly,the interaction between IMPα-9 and TPR2 was disrupted in impα-9 mutants,highlighting the critical role of a single amino acid alteration in maintaining their association.Disruption of their interaction results in the reversal of MEcPP-associated phenotypes.Chromatin immunoprecipitation coupled with sequencing analyses revealed that TPR2 binds globally to stress-response genes and suggested that IMPα-9 associates with the chromatin.They function together to suppress the expression of stress-response genes under normal conditions,but this suppression is alleviated in response to stress through the degradation of the suppressing machinery.The biological relevance of our discoveries was validated under high light stress,marked by MEcPP accumulation,elevated ASK1 levels,IMPα-9 degredation,reduced TPR2 abundance,and subsequent activation of a network of stress-response genes.In summary,our study collectively unveils fresh insights into plant adaptive mechanisms,highlighting intricate interactions among retrograde signaling,the proteasome,and nuclear transport machinery.

Effects ofβ-1,3-glucan and ascorbic acid on the nutritional-immune response and antioxidant signaling pathways of live tiger grouper during simulated transport

Transport in water is the most common method for transporting live fish in China,however,transport is a strong stressor.Transport stress could lead to a reduced immune and antioxidant system function of tiger grouper,resulting in sickness and death.Besides,tiger grouper were continuously stressed during transport,which resulted in quality deterioration.It is necessary that find a way to relieve the stress of transportation of tiger grouper.Ascorbic acid is not only a good anti-stress agent,but it is also an effective immunostimulant.β-1,3-glucan is a feed additive that can enhance the immune response of fish.Therefore,this study evaluated the effects ofβ-1,3-glucan and ascorbic acid on the nutritional-immune response and antioxidant signaling pathways of live tiger grouper during simulated transport.Results indicated that addingβ-1,3-glucan and ascorbic acid in transport-water muted the increase of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activity.In addition,β-1,3-glucan and ascorbic acid activated Nrf2 and mediated TOR expression and then up-regulate related mRNA expression of antioxidant and immune enzymes.We concluded that the application ofβ-1,3-glucan and ascorbic acid inhibit the increase of metabolism enzymes and inflammatory factors and activate immune and antioxidant signaling pathways to relieve oxidant stress,immune response,and apoptosis.Reducing the loss of amino acids provided nutrients to relieve oxidative stress and immune response,which demonstrated immune-nutritional response in live tiger grouper during simulated transport.These results may provide a new solution for alleviating the decline of immune and antioxidant function of tiger grouper caused by transportation stress.

MicroRNA regulatory pattern in spinal cord ischemia-reperfusion injury

After spinal cord injury, dysregulated miRNAs appear and can participate in inflammatory responses, as well as the inhibition of apoptosis and axon regeneration through multiple pathways. However, the functions of miRNAs in spinal cord ischemia-reperfusion injury progression remain unclear. miRCURY LNATM Arrays were used to analyze miRNA expression profiles of rats after 90 minutes of ischemia followed by reperfusion for 24 and 48 hours. Furthermore, subsequent construction of aberrantly expressed miRNA regulatory patterns involved cell survival, proliferation, and apoptosis. Remarkably, the mitogen-activated protein kinase(MAPK) signaling pathway was the most significantly enriched pathway among 24-and 48-hour groups. Bioinformatics analysis and quantitative reverse transcription polymerase chain reaction confirmed the persistent overexpression of miR-22-3 p in both groups. These results suggest that the aberrant miRNA regulatory network is possibly regulated MAPK signaling and continuously affects the physiological and biochemical status of cells, thus participating in the regulation of spinal cord ischemia-reperfusion injury. As such, miR-22-3 p may play sustained regulatory roles in spinal cord ischemia-reperfusion injury. All experimental procedures were approved by the Animal Ethics Committee of Jilin University, China [approval No. 2020(Research) 01].