V-raf-leukemia viral oncogene 1(RAF1),a serine/threonine protein kinase,is well established to play a crucial role in tumorigenesis and cell development.However,the specific role of hypothalamic RAF1 in regulating ene...V-raf-leukemia viral oncogene 1(RAF1),a serine/threonine protein kinase,is well established to play a crucial role in tumorigenesis and cell development.However,the specific role of hypothalamic RAF1 in regulating energy metabolism remains unknown.In this study,we found that the expression of RAF1 was significantly increased in hypothalamic AgRP neurons of diet-induced obesity(DIO)mice.Under normal chow diet feeding,overexpression of Raf1 in AgRP neurons led to obesity in mice characterized by increased body weight,fat mass,and impaired glucose tolerance.Conversely,Raf1 knockout in AgRP neurons protected against diet-induced obesity,reducing fat mass and improving glucose tolerance.Mechanistically,Raf1 activated the MAPK signaling pathway,culminating in the phosphorylation of cAMP response element-binding protein(CREB),which enhanced transcription of Agrp and Npy.Insulin stimulation further potentiated the RAF1-MEK1/2-ERK1/2-CREB axis,highlighting RAF1's role in integrating hormonal and nutritional signals to regulate energy balance.Collectively,these findings underscore the important role of RAF1 in AgRP neurons in maintaining energy homeostasis and obesity pathogenesis,positioning it and its downstream pathways as potential therapeutic targets for innovative strategies to combat obesity and related metabolic diseases.展开更多
Objective:To examine the protective effect of saikosaponin D against streptozotocin(STZ)-induced gestational diabetes mellitus in female rats.Methods:Intraperitoneal administration of STZ(40 mg/kg)was used for the ind...Objective:To examine the protective effect of saikosaponin D against streptozotocin(STZ)-induced gestational diabetes mellitus in female rats.Methods:Intraperitoneal administration of STZ(40 mg/kg)was used for the induction of diabetes in pregnant rats,and rats orally received sikosaponin D(10,20,and 40 mg/kg).The body weight,placental weight,fetal weight,fetal index,and various biochemical parameters,including antioxidant,glucose level,cytokines,and apoptosis parameters,were estimated.The expression levels of various mRNAs were also analyzed.Results:Saikosaponin D increased body weight and fetal weight while decreasing placental weight and placental index.Saikosaponin D significantly altered various biochemical parameters such as fasting blood glucose,glycated hemoglobin(HbA1c),hemoglobin,hepatic glycogen,advanced glycation end products,lipid parameters(total cholesterol,triglyceride,low density lipoprotein,high density lipoprotein,very low density lipoprotein),antioxidant parameters(superoxide dismutase,glutathione,glutathione peroxidase,malonaldehyde,catalase),inflammatory cytokines(tumor necrosis factor-α,interleukin-6,interleukin-1β,interleukin-10),apoptosis parameters(Bcl-2,Bax,caspase-3),resistin,adiponectin,leptin,intercellular adhesion molecule 1,vascular cell adhesion molecule-1,and monocyte chemotactic protein-1.Furthermore,saikosaponin D modulated the mRNA expression of TLR4,MyD88,NF-κB,NLRP3,TNF-α,IL-6,CRP,SIRT1,and MAPK.Conclusions:Saikosaponin D exhibits a protective effect against STZinduced gestational diabetes mellitus in rats via regulation of TLR4/MyD88/NF-κB and MAPK signaling pathways.展开更多
The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research...The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research,Vol.26,No.1,2018,pp.131–143.展开更多
Background Uterine aging is a key factor contributing to the deterioration of egg quality and reproductive performance in laying hens.Despite its importance,the molecular mechanisms underlying uterine aging remain poo...Background Uterine aging is a key factor contributing to the deterioration of egg quality and reproductive performance in laying hens.Despite its importance,the molecular mechanisms underlying uterine aging remain poorly defined.This study aimed to characterize gene expression and regulatory changes associated with uterine aging in hens at different life stages.Results Transcriptomic Analysis of uterine tissue from hens aged 350,500,And 700 d revealed dynamic changes in gene expression patterns during aging.A significant upregulation of genes involved in cellular senescence was observed,including increased expression of the p53 signaling pathway And markers associated with inflammation And cell cycle arrest.The most notable changes occurred between 350 And 500 d of age,suggesting this as a critical window for the onset of uterine aging.MicroRNA sequencing identified miR-210a-5p as significantly reduced with age.Target prediction and experimental validation showed that miR-210a-5p directly suppresses the expression of RASL11B,a Ras-like small GTPase that activates the MAPK signaling pathway.In primary uterine epithelial cells,reduced miR-210a-5p levels led to elevated RASL11B expression,increased activation of B-Raf,MEK,and ERK proteins,and enhanced expression of aging-related genes and inflammatory factors.In contrast,overexpression of miR-210a-5p or inhibition of the MAPK pathway delayed senescence and reduced inflammatory signaling.RASL11B overexpression was sufficient to induce aging phenotypes,confirming its central role in promoting uterine cellular aging.Conclusions This study identifies a novel regulatory pathway in which miR-210a-5p modulates uterine aging through the RASL11B-MAPK signaling cascade.The findings provide mechanistic insight into age-related reproductive decline in hens and suggest that targeting this pathway may offer new strategies for maintaining uterine function and extending reproductive lifespan in poultry.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection disrupts immune function by activating inflammatory pathways related to disease severity.Understanding virus-induced inflammation is crucial for dev...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection disrupts immune function by activating inflammatory pathways related to disease severity.Understanding virus-induced inflammation is crucial for developing anti-coronavirus disease 2019(COVID-19)therapies.This study used principal component analysis,heatmaps,and other tools to examine mitogen-activated protein kinase(MAPK)pathway gene expression,and found that alterations in MAPK pathway genes were correlated with immune response changes.Further analysis linked P38-related gene expression to clinical symptoms,with transcriptomic data showing a strong association between MAPK gene expression changes and SARS-CoV-2 infection.In infected cell models,phosphorylated P38(P-P38)protein and inflammatory factors were significantly upregulated.Analysis of the GSE217948 dataset showed a significant correlation between plasma markers(interferon inducible protein-10(IP-10)and interleukin(IL)-6)and symptoms(fever and fatigue).Activation of P38 appears to release inflammatory factors tied to these symptoms making P38 as a key pathway in virus-induced inflammation.Forsythin(KD-1),an anti-inflammatory compound from forsythia showed efficacy against SARS-CoV-2,inhibiting replication,reducing P38 levels,and lowering inflammatory markers(IL-6,IL-8,IP-10,tumor necrosis factor-α(TNF-α),and monocyte chemotactic protein-1(MCP-1))in both cell and animal models.In specific cell models,KD-1 blocked P38 activation,thereby reducing inflammation.In a P38 overexpression model,KD-1 decreased P38 phosphorylation and downstream inflammatory proteins.This study identifies the P38 pathway as a therapeutic target for COVID-19,supporting KD-1’s potential in mitigating virus-induced inflammation and guiding further research into anti-inflammatory treatments for respiratory viruses.展开更多
The published article titled“Procaine inhibits the proliferation and migration of colon cancer cells through inactivation of the ERK/MAPK/FAK pathways by regulation of RhoA”has been retracted from Oncology Research,...The published article titled“Procaine inhibits the proliferation and migration of colon cancer cells through inactivation of the ERK/MAPK/FAK pathways by regulation of RhoA”has been retracted from Oncology Research,Vol.26,No.2,2018,pp.209–217.展开更多
Colorectal cancer(CRC)is one of the most common malignancies.In recent years,despite the widespread application of new endoscopic techniques and continuous advancements in treatment methods that have improved the earl...Colorectal cancer(CRC)is one of the most common malignancies.In recent years,despite the widespread application of new endoscopic techniques and continuous advancements in treatment methods that have improved the early diagnosis rate of CRC,the disease often has an insidious onset.Many patients are already in the middle or late stages of the disease when diagnosed,leading to poor treatment outcomes and prognosis.Therefore,further investigation into the pathogenesis of CRC and exploration of new therapeutic targets remain hot topics of research.The mitogen-activated protein kinase(MAPK)signaling pathway belongs to the large family of serine/threonine kinases and is a crucial pathway for signal transduction in eukaryotes.The MAPK signaling pathway can be activated by various extracellular signals such as cytokines,growth factors,and oxidative stress,thereby influencing biological processes like cell cycle,differentiation,malignant transformation,metastatic potential,and apoptosis.It plays a significant regulatory role in the development and progression of malignancies[1].The evolution of CRC involves abnormal regulation of multiple signaling pathways,among which dysregulation of the MAPK signaling pathway is a key molecular event.This article provides a comprehensive overview of the research progress on the MAPK signaling pathway in CRC.展开更多
Objective:To characterize the tumor-suppressive role of LINC00936 in non-small cell lung cancer(NSCLC)through mechanistic exploration of its regulatory pathways.Methods:Bioinformatics interrogation of TCGA/NSCLC cohor...Objective:To characterize the tumor-suppressive role of LINC00936 in non-small cell lung cancer(NSCLC)through mechanistic exploration of its regulatory pathways.Methods:Bioinformatics interrogation of TCGA/NSCLC cohorts assessed LINC00936 expression,clinical correlations,and immune contexture.Functional enrichment analyses predicted pathway associations.In H1299 cells,LINC00936 overexpression(plasmid)and knockdown(siRNA)models were validated by RT-qPCR.Transcriptomic profiling identified differentially expressed genes(DEGs)subjected to KEGG pathway analysis.Results:LINC00936 was significantly downregulated in NSCLC tissues(TCGA,P<0.05)and cell lines(vs.16-HBE,P<0.05),correlating with poor prognosis and altered tumor-infiltrating immune subsets.DEG enrichment implicated Ras/MAPK signaling as the dominant pathway(FDR<0.05).Successful LINC00936 modulation(overexpression/knockdown,P<0.05)confirmed its regulatory capacity.Conclusion:LINC00936 acts as a tumor suppressor in NSCLC via Ras/MAPK pathway modulation,proposing its therapeutic candidacy for precision oncology strategies.展开更多
Introduction:Acral melanoma(AM)is the predominant subtype of cutaneous melanoma in Asian populations,characterized by more aggressive clinical features and limited neoadjuvant therapy response.Centrosomal protein 55 k...Introduction:Acral melanoma(AM)is the predominant subtype of cutaneous melanoma in Asian populations,characterized by more aggressive clinical features and limited neoadjuvant therapy response.Centrosomal protein 55 kDa(CEP55)has been implicated in the pathogenesis of various malignancies,but its role in AM remains undefined.Methods:CEP55 expression in melanoma tissues and cell lines was analyzed by RT-qPCR,Western blotting,and immunohistochemistry(IHC).Databases(GEPIA,Sangerbox,Kaplan-Meier plotter,and TIMER)were used to analyze the expression of CEP55 and its correlation with clinical data of melanoma patients.Functional assays were conducted in vitro and in vivo.RNA sequencing(RNA-seq)and rescue experiments were used to explore underlying mechanisms.Tissue microarrays were used to verify the relationship between CEP55 and immune checkpoints.Results:CEP55 overexpression is associated with Breslow thickness and TNM stage in melanoma tissues and cell lines.CEP55 knockdown inhibited melanoma cell proliferation,migration,and invasion.And CEP55 activated mitogen-activated protein kinase(MAPK)signaling,leading to BRAF inhibitor resistance.Besides,CEP55 overexpression was associated with more favorable responses to immunotherapy in melanoma patients.Conclusions:CEP55 plays a critical role in AM progression and immunotherapy.Targeting CEP55 may be a promising therapeutic strategy for AM.展开更多
AIM:To investigate the effects of a Chinese medicine formula“Qingxuan Runmu Yin”(QRY)on ocular surface inflammation in a rat model of dry eye,and its mechanism via the toll-like receptor 4(TLR4)/transforming growth ...AIM:To investigate the effects of a Chinese medicine formula“Qingxuan Runmu Yin”(QRY)on ocular surface inflammation in a rat model of dry eye,and its mechanism via the toll-like receptor 4(TLR4)/transforming growth factor kinase 1(TAK1)/p38 mitogen-activated protein kinase(p38MAPK)signaling pathway.METHODS:Seventy-two Sprague-Dawley rats were randomly divided into six groups(n=12 each):the control group,model group,3 groups of QRY(with low-,medium-,and high-doses),and SB203580 group.Dry eye was induced using benzalkonium chloride.Schirmer’s test(SIT)and corneal fluorescein staining(CFS)were performed every 14d throughout the experiment.Histopathological changes in corneal and conjunctival tissues were observed using hematoxylin and eosin(HE)and periodic acid-Schiff(PAS)staining.Protein expression levels of key inflammatory markers and signaling pathway targets were assessed via immunohistochemistry,ELISA,and Western blotting.RESULTS:Compared to the control group,the model group showed significant reductions in SIT and increases in CFS scores,alongside structural disorganization of corneal/conjunctival tissues,decreased conjunctival goblet cell(CGC)numbers,and elevated expression of inflammatory markers[interleukin(IL)-1β,IL-6,tumor necrosis factoralpha(TNF-α),matrix metalloproteinase-9(MMP9)]and pathway proteins(TLR4,p-TAK1,p-p38MAPK;P<0.05).Treatment with QRY(low,medium,and high doses)and SB203580 significantly improved SIT scores,reduced CFS scores,restored corneoconjunctival structure,increased CGC numbers,and decreased expression levels of IL-1β,IL-6,TNF-α,MMP9,TLR4,p-TAK1,and p-p38MAPK proteins compared to the model group(P<0.05).CONCLUSION:QRY may alleviate ocular surface inflammation associated with dry eye by inhibiting the TLR4/TAK1/p38MAPK signaling pathway,highlighting its potential therapeutic efficacy for dry eye.展开更多
Inflammation underlies many chronic diseases,and inflammatory bowel disease(IBD)is a condition characterized by long-term inflammation of the gut.Egg whites have been shown to contain many beneficial active substances...Inflammation underlies many chronic diseases,and inflammatory bowel disease(IBD)is a condition characterized by long-term inflammation of the gut.Egg whites have been shown to contain many beneficial active substances.Therefore,we obtained 2 peptides from salted egg white:Val-Val-His-Phe(VF-4)and Asp-Thr-Gln-Ala-Met-Pro-Phe-Arg(DR-8).The sodium dextran sulfate(DSS)-induced mice colitis model was used to evaluate its regulatory effect on colitis in vivo.The results showed that VF-4 and DR-8 improved the clinical symptoms of DSS-induced colitis,attenuated colon tissue damage,inhibited the activation of nuclear factor kappa-B(NF-κB)/mitogen-activated protein kinase(MAPK)/phosphoinositide 3-kinase-Akt(PI3K-AKT)signaling pathways,and inhibited the expression of inflammatory cytokines.16S rRNA gene sequencing showed that VF-4 and DR-8 administration increased the relative abundance of intestinal beneficial bacteria including Lactobacillus,Blautia,and down-regulated the relative abundance of inflammation-related bacteria including Acinetobacter,Lachnospiraceae_NK4A136_group,Klebsiella.Moreover,the degree of correlation between pro-inflammatory cytokines and microbiota was as follows:interleukin-6(IL-6)>tumor necrosis factor-α(TNF-α)>interleukin-1β(IL-1β)>interferon-γ(IFN-γ).In conclusion,this study suggests that salted egg white peptides VF-4 and DR-8 have a significant antiinflammatory effect in vivo.It also provides a strategy for the treatment of IBD and a new way for the highvalue utilization of salted egg white.展开更多
Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins.However,the underlying mechanism(s)remain not completely understood.The aim ...Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins.However,the underlying mechanism(s)remain not completely understood.The aim of this study is thus to elucidate the possible mechanisms related to the melanogenesis suppression by glabridin in cultured B16 murine melanoma cells and in UVA radiation induced hyperpigmentation model of BALB/c mice as well.Molecular docking simulations revealed that between catalytic core residues and the compound.The treatment by glabridin significantly downregulated both transcriptional and/or protein expression of melanogenesis-related factors including melanocyte stimulating hormone receptor(MC1R),microphthalmia-associated transcription factor(MITF),tyrosinase(TYR),TYR-related protein-1(TRP-1)and TRP-2 in B16 cells.Both PKA/MITF and MAPK/MITF signaling pathways were found to be involved in the suppression of melanogenesis by glabridin in B16 cells.Also in vivo glabridin therapy significantly reduced hyperpigmentation,epidermal thickening,roughness and inflammation induced by frequent UVA exposure in mice skins,thus beneficial for skin healthcare.These data further look insights into the molecular mechanisms of melanogenesis suppression by glabridin,rationalizing the application of the natural compound for skin healthcare.展开更多
Both tea polyphenols and selenium(Se)have been suggested to exert the health benefits via the regulatory capacities of chronic inflammation,which make Se-enriched oolong tea a promising beverage as an anti-inflammator...Both tea polyphenols and selenium(Se)have been suggested to exert the health benefits via the regulatory capacities of chronic inflammation,which make Se-enriched oolong tea a promising beverage as an anti-inflammatory diet.The aim of this study is to investigate the anti-inflammatory effects of Se-enriched oolong tea extract(Se-TE)and underlying mechanism in lipopolysaccharide(LPS)-induced RAW264.7 cells.Se-TE treatments(50 and 150μg/m L)significantly suppressed the over-production of nitric oxide(NO)and prostaglandin E2(PGE2)in LPS-stimulated macrophages via downregulating the expression of nitric oxide synthase(i NOS)and cyclooxygenase-2(COX-2).Moreover,Se-TEs also effectively inhibited the productions of inflammatory cytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β).Furthermore,Se-TE could block mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signaling pathways through the inhibition of the phosphorylation of key proteins(IκB-α,p65,p38,ERK,and JNK)and the translocation of the p65 subunit into the nucleus.Collectively,our results indicated that Se-TE may have the potential to be used as a novel food ingredient for the development of various anti-inflammatory foods and the treatment and prevention of chronic inflammation-related diseases.展开更多
Two immunomodulatory polysaccharides(Vp2a-Ⅱ and Vp3) were isolated and identified from Apocynum venetum L. flowers, and their innate immune-stimulating functions and working mechanisms were evaluated in RAW264.7 cell...Two immunomodulatory polysaccharides(Vp2a-Ⅱ and Vp3) were isolated and identified from Apocynum venetum L. flowers, and their innate immune-stimulating functions and working mechanisms were evaluated in RAW264.7 cells. Both the level of released nitric oxide(NO) and expression of inducible nitric oxide synthase(iNOS) m RNA were significantly enhanced in the RAW264.7 macrophages cells treated by Vp2a-Ⅱ and Vp3. Vp2a-Ⅱ(100–800 μg/m L) and Vp3(400 μg/mL) could significantly increase the phagocytic activity of RAW264.7 cells and the secretion and m RNA expression of TNF-α and IL-6 in a concentrationdependent manner through affecting mitogen-activated protein kinase(MAPK) activity and nuclear factor κB(NF-κB) nuclear translocation. Vp2a-Ⅱ might activate the MAPK signaling pathways and induce the nuclear translocation of NF-κB p65, whilst Vp3 likely activated the NF-κB and MAPK signaling pathways without influencing the p38 MAPK route.展开更多
Nasopharyngeal carcinoma(NPC)is the third most common malignancy with a high recurrence and metastasis rate in South China.Natural compounds extracted from traditional Chinese herbal medicines have been developed and ...Nasopharyngeal carcinoma(NPC)is the third most common malignancy with a high recurrence and metastasis rate in South China.Natural compounds extracted from traditional Chinese herbal medicines have been developed and utilized for the treatment of a variety of cancers with modest properties and slight side effects.Maackiain(MA)is a type of flavonoid that was first isolated from leguminous plants,and it has been reported to relieve various nervous system disorders and exert anti-allergic as well as antiinflammatory effects.In this study,we demonstrated that MA inhibited proliferation,arrested cell cycle and induced apoptosis in nasopharyngeal carcinoma CNE1 and CNE2 cells in vitro and in vivo.The expression of the related proteins associated with these processes were consistent with the above effects.Moreover,transcriptome sequencing and subsequent Western blot experiments revealed that inhibition of the MAPK/Ras pathway may be responsible to the anti-tumor effect of MA on NPC cells.Therefore,the effects of MA and an activator of this pathway,tertiary butylhydroquinone(TBHQ),alone or combination,were investigated.The results showed TBHQ neutralized the inhibitory effects of MA.These data suggest that MA exerts its anti-tumor effect by inhibiting the MAPK/Ras signaling pathway and it has the potential to become a treatment for patients with NPC.展开更多
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 ...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.展开更多
Botrytis cinerea is a typical necrotrophic pathogenic fungus that causes severe diseases in a wide range of plant species, leading to significant economic losses. Our previous study showed that BcSDR1 positively regul...Botrytis cinerea is a typical necrotrophic pathogenic fungus that causes severe diseases in a wide range of plant species, leading to significant economic losses. Our previous study showed that BcSDR1 positively regulates growth,development, and pathogenicity of B. cinerea. However, the regulation mechanism of BcSDR1 and the relationship between BcSDR1 and cAMP and MAPK signaling pathways are not well understood. In this study, transcriptome data showed that BcSDR1 is involved in glucose transmembrane transport, signal transduction, secondary metabolism, and other biological processes. BcSDR1 mutant(BCt41) showed remarkably weak sensitivity to cAMP and MAPK signaling pathways specific inhibitors, SQ22536 and U0126, and significantly decreased cAMP content. The key genes of cAMP and MAPK signaling pathways, BcGB1, BcBTP1, BcBOS1, BcRAS1, and BcBMP3 were significantly upregulated,whereas BcPLC1, BcBCG1, BcCDC4, BcSAK1, BcATF1, and BcBAP1 were significantly downregulated(P<0.05).BcSDR1 was obviously upregulated in BcBCG2, BcBCG3, BcPKA1, and BcPKAR RNA interference(RNAi) mutants, but significantly downregulated in BcPKA2, BcBMP1, and BcBMP3 RNAi mutants. Thus, BcBCG2, BcBCG3, BcPKA1, and BcPKAR negatively regulate BcSDR1 expression, whereas BcPKA2, BcBMP1, and BcBMP3 positively regulate BcSDR1expression.展开更多
Cyanidin-3-glucoside(C3G)is the most common anthocyanin in dark grains and berries and is a food functional factor to improve visual health.However,the mechanisms of C3G on blue light-induced retinal pigment epithelia...Cyanidin-3-glucoside(C3G)is the most common anthocyanin in dark grains and berries and is a food functional factor to improve visual health.However,the mechanisms of C3G on blue light-induced retinal pigment epithelial(RPE)cell photooxidative damage needs further exploration.We investigated the effects of C3G on blue light-irradiated A2E-containing RPE cells and explored whether sphingolipid,mitogen-activated protein kinase(MAPK),and mitochondria-mediated pathways are involved in this mechanism.Blue light irradiation led to mitochondria and lysosome damage in RPE cells,whereas C3G preserved mitochondrial morphology and function and maintained the lysosomal integrity.C3G suppressed the phosphorylation of JNK and p38 MAPK and mitochondria-mediated pathways to inhibit RPE cell apoptosis.Lipidomics data showed that C3G protected RPE cells against blue light-induced lipid peroxidation and apoptosis by maintaining sphingolipids balance.C3G significantly inhibited ceramide(Cer d18:0/15:0,Cer d18:0/16:0 and Cer d18:0/18:0)accumulation and elevated galactosylceramide(GalCer d18:1/15:0 and GalCer d18:1/16:0)levels in the irradiated A2E-containing RPE cells.Furthermore,C3G attenuated cell membrane damage by increasing phosphatidylcholine and phosphatidylserine levels.C3G inhibited apoptosis and preserved the structure of mitochondria and lysosome by regulating sphingolipid signaling and suppression of MAPK activation in RPE cells.Thus,dietary supplementation of C3G prevents retinal photooxidative damage.展开更多
Background:Natural astaxanthin(ASTA)has strong antioxidant properties and has been widely used as a health product to improve human health.However,the effects of ASTA on the reproductive performance of aging roosters ...Background:Natural astaxanthin(ASTA)has strong antioxidant properties and has been widely used as a health product to improve human health.However,the effects of ASTA on the reproductive performance of aging roosters have been poorly studied.We aimed to investigate the effects of dietary ASTA on semen quality and antioxidant capacity in aging roosters and to explore the potential mechanism of semen quality change via antioxidation defense system.Methods:In the present study,9653-week-old Jinghong No.1 layer breeder roosters were fed a corn-soybean meal basal diet containing 0,25,50,or 100 mg/kg ASTA for 6 weeks.Results:Semen quality in the ASTA groups remarkably improved than that in the control group,and antioxidant activities,the abilities to scavenge hydroxyl radicals and superoxide anions,increased gradually with ASTA addition(P<0.05).In addition,the mRNA levels of antioxidant enzymes as well as the mRNA and protein levels of the mitogen-activated protein kinase(MAPK)and nuclear factor-erythroid 2-related factor 2(Nrf2)were markedly increased in the 50-100 mg/kg ASTA group(P<0.05).Conclusions:Collectively,these results demonstrate that dietary ASTA may improve semen quality by increasing antioxidant enzyme activities and the ability to scavenge hydroxyl radicals,which may be related to upregulation of the MAPK/Nrf2 pathway.展开更多
Objective:To evaluate the antiviral activity and phytochemicals of selected plant extracts and their effect on the mitogen-activated protein kinase(MAPK)signaling pathway modulated by hepatitis C virus(HCV)nonstructur...Objective:To evaluate the antiviral activity and phytochemicals of selected plant extracts and their effect on the mitogen-activated protein kinase(MAPK)signaling pathway modulated by hepatitis C virus(HCV)nonstructural protein 5 A(NS5A).Methods:A total of ten plant extracts were initially screened for their toxicities against Hep G2 cells.The non-toxic plants were tested for their inhibitory effect on the expression of HCV NS5A at both m RNA and protein levels using real-time PCR and Western blotting assays,respectively.The differential expression of the genes associated with MAPK pathway in the presence of NS5A gene and plant extract was measured through real-time PCR.Subsequently,the identification of secondary metabolites was carried out by phytochemical and HPLC analysis.Results:The phytochemical profiling of Berberis lyceum revealed the presence of alkaloids,phenols,saponins,tannins,flavonoids,carbohydrates,terpenoids,steroids,and glycosides.Similarly,quercetin,myricetin,gallic acid,caffeic acid,and ferulic acid were identified through HPLC analysis.The methanolic extract of Berberis lyceum strongly inhibited HCV RNA replication with an IC50 of 11.44μg/m L.RT-PCR and Western blotting assays showed that the extract reduced the expression of HCV NS5A in a dosedependent manner.Berberis lyceum extract also attenuated NS5A-induced dysregulation of the MAPK signaling pathway.Conclusions:Our findings suggest that Berberis lyceum extract strongly inhibits HCV propagation by reducing HCV NS5A-induced perturbation of MAPK signaling.展开更多
基金support from various sources,including the National Natural Science Foundation of China(Grant Nos.81570774,82070872,92049118,and 82370854)the Junior Thousand Talents Program of China,and the Nanjing Medical University Startup Fund(All awarded to J.L.)support provided by Jiangsu Province's Innovation Personal as well as Innovative and Entrepreneurial Team of Jiangsu Province(Grant No.JSSCTD2021)(All awarded to J.L.).
文摘V-raf-leukemia viral oncogene 1(RAF1),a serine/threonine protein kinase,is well established to play a crucial role in tumorigenesis and cell development.However,the specific role of hypothalamic RAF1 in regulating energy metabolism remains unknown.In this study,we found that the expression of RAF1 was significantly increased in hypothalamic AgRP neurons of diet-induced obesity(DIO)mice.Under normal chow diet feeding,overexpression of Raf1 in AgRP neurons led to obesity in mice characterized by increased body weight,fat mass,and impaired glucose tolerance.Conversely,Raf1 knockout in AgRP neurons protected against diet-induced obesity,reducing fat mass and improving glucose tolerance.Mechanistically,Raf1 activated the MAPK signaling pathway,culminating in the phosphorylation of cAMP response element-binding protein(CREB),which enhanced transcription of Agrp and Npy.Insulin stimulation further potentiated the RAF1-MEK1/2-ERK1/2-CREB axis,highlighting RAF1's role in integrating hormonal and nutritional signals to regulate energy balance.Collectively,these findings underscore the important role of RAF1 in AgRP neurons in maintaining energy homeostasis and obesity pathogenesis,positioning it and its downstream pathways as potential therapeutic targets for innovative strategies to combat obesity and related metabolic diseases.
文摘Objective:To examine the protective effect of saikosaponin D against streptozotocin(STZ)-induced gestational diabetes mellitus in female rats.Methods:Intraperitoneal administration of STZ(40 mg/kg)was used for the induction of diabetes in pregnant rats,and rats orally received sikosaponin D(10,20,and 40 mg/kg).The body weight,placental weight,fetal weight,fetal index,and various biochemical parameters,including antioxidant,glucose level,cytokines,and apoptosis parameters,were estimated.The expression levels of various mRNAs were also analyzed.Results:Saikosaponin D increased body weight and fetal weight while decreasing placental weight and placental index.Saikosaponin D significantly altered various biochemical parameters such as fasting blood glucose,glycated hemoglobin(HbA1c),hemoglobin,hepatic glycogen,advanced glycation end products,lipid parameters(total cholesterol,triglyceride,low density lipoprotein,high density lipoprotein,very low density lipoprotein),antioxidant parameters(superoxide dismutase,glutathione,glutathione peroxidase,malonaldehyde,catalase),inflammatory cytokines(tumor necrosis factor-α,interleukin-6,interleukin-1β,interleukin-10),apoptosis parameters(Bcl-2,Bax,caspase-3),resistin,adiponectin,leptin,intercellular adhesion molecule 1,vascular cell adhesion molecule-1,and monocyte chemotactic protein-1.Furthermore,saikosaponin D modulated the mRNA expression of TLR4,MyD88,NF-κB,NLRP3,TNF-α,IL-6,CRP,SIRT1,and MAPK.Conclusions:Saikosaponin D exhibits a protective effect against STZinduced gestational diabetes mellitus in rats via regulation of TLR4/MyD88/NF-κB and MAPK signaling pathways.
文摘The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research,Vol.26,No.1,2018,pp.131–143.
基金funded by the National Key Research and Development Program of China,grant number 2021YFD1300600Sichuan Science and Technology Program(2024YFNH0025,2022YFYZ0005,2021YFYZ0031)China Agriculture Research System of MOF and MARA(CARS-40).
文摘Background Uterine aging is a key factor contributing to the deterioration of egg quality and reproductive performance in laying hens.Despite its importance,the molecular mechanisms underlying uterine aging remain poorly defined.This study aimed to characterize gene expression and regulatory changes associated with uterine aging in hens at different life stages.Results Transcriptomic Analysis of uterine tissue from hens aged 350,500,And 700 d revealed dynamic changes in gene expression patterns during aging.A significant upregulation of genes involved in cellular senescence was observed,including increased expression of the p53 signaling pathway And markers associated with inflammation And cell cycle arrest.The most notable changes occurred between 350 And 500 d of age,suggesting this as a critical window for the onset of uterine aging.MicroRNA sequencing identified miR-210a-5p as significantly reduced with age.Target prediction and experimental validation showed that miR-210a-5p directly suppresses the expression of RASL11B,a Ras-like small GTPase that activates the MAPK signaling pathway.In primary uterine epithelial cells,reduced miR-210a-5p levels led to elevated RASL11B expression,increased activation of B-Raf,MEK,and ERK proteins,and enhanced expression of aging-related genes and inflammatory factors.In contrast,overexpression of miR-210a-5p or inhibition of the MAPK pathway delayed senescence and reduced inflammatory signaling.RASL11B overexpression was sufficient to induce aging phenotypes,confirming its central role in promoting uterine cellular aging.Conclusions This study identifies a novel regulatory pathway in which miR-210a-5p modulates uterine aging through the RASL11B-MAPK signaling cascade.The findings provide mechanistic insight into age-related reproductive decline in hens and suggest that targeting this pathway may offer new strategies for maintaining uterine function and extending reproductive lifespan in poultry.
基金supported by the National Administration of Traditional Chinese Medicine(ZYYCXTU-D-202201 and ZYYCXTU-D-202206)the National Natural Science Foundation of China(82474155,82174053,82141201,and 82341099)+3 种基金the Guangdong Basic and Applied Basic Research Foundation(2022A1515010301)the Macao Science and Technology Development Fund(0022/2021/A1)the Young Top Talent of Science and Technology Innovation Department of Guangdong Province(2021TQ060189)the Youth Lift Project of China Association for Science and Technology(2020-2022QNRC001).
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection disrupts immune function by activating inflammatory pathways related to disease severity.Understanding virus-induced inflammation is crucial for developing anti-coronavirus disease 2019(COVID-19)therapies.This study used principal component analysis,heatmaps,and other tools to examine mitogen-activated protein kinase(MAPK)pathway gene expression,and found that alterations in MAPK pathway genes were correlated with immune response changes.Further analysis linked P38-related gene expression to clinical symptoms,with transcriptomic data showing a strong association between MAPK gene expression changes and SARS-CoV-2 infection.In infected cell models,phosphorylated P38(P-P38)protein and inflammatory factors were significantly upregulated.Analysis of the GSE217948 dataset showed a significant correlation between plasma markers(interferon inducible protein-10(IP-10)and interleukin(IL)-6)and symptoms(fever and fatigue).Activation of P38 appears to release inflammatory factors tied to these symptoms making P38 as a key pathway in virus-induced inflammation.Forsythin(KD-1),an anti-inflammatory compound from forsythia showed efficacy against SARS-CoV-2,inhibiting replication,reducing P38 levels,and lowering inflammatory markers(IL-6,IL-8,IP-10,tumor necrosis factor-α(TNF-α),and monocyte chemotactic protein-1(MCP-1))in both cell and animal models.In specific cell models,KD-1 blocked P38 activation,thereby reducing inflammation.In a P38 overexpression model,KD-1 decreased P38 phosphorylation and downstream inflammatory proteins.This study identifies the P38 pathway as a therapeutic target for COVID-19,supporting KD-1’s potential in mitigating virus-induced inflammation and guiding further research into anti-inflammatory treatments for respiratory viruses.
文摘The published article titled“Procaine inhibits the proliferation and migration of colon cancer cells through inactivation of the ERK/MAPK/FAK pathways by regulation of RhoA”has been retracted from Oncology Research,Vol.26,No.2,2018,pp.209–217.
文摘Colorectal cancer(CRC)is one of the most common malignancies.In recent years,despite the widespread application of new endoscopic techniques and continuous advancements in treatment methods that have improved the early diagnosis rate of CRC,the disease often has an insidious onset.Many patients are already in the middle or late stages of the disease when diagnosed,leading to poor treatment outcomes and prognosis.Therefore,further investigation into the pathogenesis of CRC and exploration of new therapeutic targets remain hot topics of research.The mitogen-activated protein kinase(MAPK)signaling pathway belongs to the large family of serine/threonine kinases and is a crucial pathway for signal transduction in eukaryotes.The MAPK signaling pathway can be activated by various extracellular signals such as cytokines,growth factors,and oxidative stress,thereby influencing biological processes like cell cycle,differentiation,malignant transformation,metastatic potential,and apoptosis.It plays a significant regulatory role in the development and progression of malignancies[1].The evolution of CRC involves abnormal regulation of multiple signaling pathways,among which dysregulation of the MAPK signaling pathway is a key molecular event.This article provides a comprehensive overview of the research progress on the MAPK signaling pathway in CRC.
文摘Objective:To characterize the tumor-suppressive role of LINC00936 in non-small cell lung cancer(NSCLC)through mechanistic exploration of its regulatory pathways.Methods:Bioinformatics interrogation of TCGA/NSCLC cohorts assessed LINC00936 expression,clinical correlations,and immune contexture.Functional enrichment analyses predicted pathway associations.In H1299 cells,LINC00936 overexpression(plasmid)and knockdown(siRNA)models were validated by RT-qPCR.Transcriptomic profiling identified differentially expressed genes(DEGs)subjected to KEGG pathway analysis.Results:LINC00936 was significantly downregulated in NSCLC tissues(TCGA,P<0.05)and cell lines(vs.16-HBE,P<0.05),correlating with poor prognosis and altered tumor-infiltrating immune subsets.DEG enrichment implicated Ras/MAPK signaling as the dominant pathway(FDR<0.05).Successful LINC00936 modulation(overexpression/knockdown,P<0.05)confirmed its regulatory capacity.Conclusion:LINC00936 acts as a tumor suppressor in NSCLC via Ras/MAPK pathway modulation,proposing its therapeutic candidacy for precision oncology strategies.
基金supported by CAMS Innovation Fund for Medical Sciences(CIFMS)(2024-I2M-C&T-B-089)National Key Research and Development Program(2022YFC2504700,2022YFC2504701,2022YFC2504705)National Natural Science Foundation of China(NSFC81872216).
文摘Introduction:Acral melanoma(AM)is the predominant subtype of cutaneous melanoma in Asian populations,characterized by more aggressive clinical features and limited neoadjuvant therapy response.Centrosomal protein 55 kDa(CEP55)has been implicated in the pathogenesis of various malignancies,but its role in AM remains undefined.Methods:CEP55 expression in melanoma tissues and cell lines was analyzed by RT-qPCR,Western blotting,and immunohistochemistry(IHC).Databases(GEPIA,Sangerbox,Kaplan-Meier plotter,and TIMER)were used to analyze the expression of CEP55 and its correlation with clinical data of melanoma patients.Functional assays were conducted in vitro and in vivo.RNA sequencing(RNA-seq)and rescue experiments were used to explore underlying mechanisms.Tissue microarrays were used to verify the relationship between CEP55 and immune checkpoints.Results:CEP55 overexpression is associated with Breslow thickness and TNM stage in melanoma tissues and cell lines.CEP55 knockdown inhibited melanoma cell proliferation,migration,and invasion.And CEP55 activated mitogen-activated protein kinase(MAPK)signaling,leading to BRAF inhibitor resistance.Besides,CEP55 overexpression was associated with more favorable responses to immunotherapy in melanoma patients.Conclusions:CEP55 plays a critical role in AM progression and immunotherapy.Targeting CEP55 may be a promising therapeutic strategy for AM.
基金Supported by National Natural Science Foundation of China(No.81973908)Natural Science Foundation of Heilongjiang Province(No.PL2024H224)Postgraduate Innovation Fund of Heilongjiang University of Chinese Medicine(No.2023yjscx018).
文摘AIM:To investigate the effects of a Chinese medicine formula“Qingxuan Runmu Yin”(QRY)on ocular surface inflammation in a rat model of dry eye,and its mechanism via the toll-like receptor 4(TLR4)/transforming growth factor kinase 1(TAK1)/p38 mitogen-activated protein kinase(p38MAPK)signaling pathway.METHODS:Seventy-two Sprague-Dawley rats were randomly divided into six groups(n=12 each):the control group,model group,3 groups of QRY(with low-,medium-,and high-doses),and SB203580 group.Dry eye was induced using benzalkonium chloride.Schirmer’s test(SIT)and corneal fluorescein staining(CFS)were performed every 14d throughout the experiment.Histopathological changes in corneal and conjunctival tissues were observed using hematoxylin and eosin(HE)and periodic acid-Schiff(PAS)staining.Protein expression levels of key inflammatory markers and signaling pathway targets were assessed via immunohistochemistry,ELISA,and Western blotting.RESULTS:Compared to the control group,the model group showed significant reductions in SIT and increases in CFS scores,alongside structural disorganization of corneal/conjunctival tissues,decreased conjunctival goblet cell(CGC)numbers,and elevated expression of inflammatory markers[interleukin(IL)-1β,IL-6,tumor necrosis factoralpha(TNF-α),matrix metalloproteinase-9(MMP9)]and pathway proteins(TLR4,p-TAK1,p-p38MAPK;P<0.05).Treatment with QRY(low,medium,and high doses)and SB203580 significantly improved SIT scores,reduced CFS scores,restored corneoconjunctival structure,increased CGC numbers,and decreased expression levels of IL-1β,IL-6,TNF-α,MMP9,TLR4,p-TAK1,and p-p38MAPK proteins compared to the model group(P<0.05).CONCLUSION:QRY may alleviate ocular surface inflammation associated with dry eye by inhibiting the TLR4/TAK1/p38MAPK signaling pathway,highlighting its potential therapeutic efficacy for dry eye.
基金the financial support provided by the Project of Jiangxi Provincial Department of Education,China(GJJ200433)。
文摘Inflammation underlies many chronic diseases,and inflammatory bowel disease(IBD)is a condition characterized by long-term inflammation of the gut.Egg whites have been shown to contain many beneficial active substances.Therefore,we obtained 2 peptides from salted egg white:Val-Val-His-Phe(VF-4)and Asp-Thr-Gln-Ala-Met-Pro-Phe-Arg(DR-8).The sodium dextran sulfate(DSS)-induced mice colitis model was used to evaluate its regulatory effect on colitis in vivo.The results showed that VF-4 and DR-8 improved the clinical symptoms of DSS-induced colitis,attenuated colon tissue damage,inhibited the activation of nuclear factor kappa-B(NF-κB)/mitogen-activated protein kinase(MAPK)/phosphoinositide 3-kinase-Akt(PI3K-AKT)signaling pathways,and inhibited the expression of inflammatory cytokines.16S rRNA gene sequencing showed that VF-4 and DR-8 administration increased the relative abundance of intestinal beneficial bacteria including Lactobacillus,Blautia,and down-regulated the relative abundance of inflammation-related bacteria including Acinetobacter,Lachnospiraceae_NK4A136_group,Klebsiella.Moreover,the degree of correlation between pro-inflammatory cytokines and microbiota was as follows:interleukin-6(IL-6)>tumor necrosis factor-α(TNF-α)>interleukin-1β(IL-1β)>interferon-γ(IFN-γ).In conclusion,this study suggests that salted egg white peptides VF-4 and DR-8 have a significant antiinflammatory effect in vivo.It also provides a strategy for the treatment of IBD and a new way for the highvalue utilization of salted egg white.
基金supported by the Inner Mongolia Autonomous Region Science and Technology Revitalization Foundation (2021CG0029)the National Natural Science Foundation of China (22178070)
文摘Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins.However,the underlying mechanism(s)remain not completely understood.The aim of this study is thus to elucidate the possible mechanisms related to the melanogenesis suppression by glabridin in cultured B16 murine melanoma cells and in UVA radiation induced hyperpigmentation model of BALB/c mice as well.Molecular docking simulations revealed that between catalytic core residues and the compound.The treatment by glabridin significantly downregulated both transcriptional and/or protein expression of melanogenesis-related factors including melanocyte stimulating hormone receptor(MC1R),microphthalmia-associated transcription factor(MITF),tyrosinase(TYR),TYR-related protein-1(TRP-1)and TRP-2 in B16 cells.Both PKA/MITF and MAPK/MITF signaling pathways were found to be involved in the suppression of melanogenesis by glabridin in B16 cells.Also in vivo glabridin therapy significantly reduced hyperpigmentation,epidermal thickening,roughness and inflammation induced by frequent UVA exposure in mice skins,thus beneficial for skin healthcare.These data further look insights into the molecular mechanisms of melanogenesis suppression by glabridin,rationalizing the application of the natural compound for skin healthcare.
基金funded by Fujian Special Research Projects for Public Scientific Research Institutions(grant number 2020R1032001)。
文摘Both tea polyphenols and selenium(Se)have been suggested to exert the health benefits via the regulatory capacities of chronic inflammation,which make Se-enriched oolong tea a promising beverage as an anti-inflammatory diet.The aim of this study is to investigate the anti-inflammatory effects of Se-enriched oolong tea extract(Se-TE)and underlying mechanism in lipopolysaccharide(LPS)-induced RAW264.7 cells.Se-TE treatments(50 and 150μg/m L)significantly suppressed the over-production of nitric oxide(NO)and prostaglandin E2(PGE2)in LPS-stimulated macrophages via downregulating the expression of nitric oxide synthase(i NOS)and cyclooxygenase-2(COX-2).Moreover,Se-TEs also effectively inhibited the productions of inflammatory cytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β).Furthermore,Se-TE could block mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signaling pathways through the inhibition of the phosphorylation of key proteins(IκB-α,p65,p38,ERK,and JNK)and the translocation of the p65 subunit into the nucleus.Collectively,our results indicated that Se-TE may have the potential to be used as a novel food ingredient for the development of various anti-inflammatory foods and the treatment and prevention of chronic inflammation-related diseases.
基金supported by Research on Precision Nutrition and Health Food,Department of Science and Technology of Henan Province(CXJD2021006)。
文摘Two immunomodulatory polysaccharides(Vp2a-Ⅱ and Vp3) were isolated and identified from Apocynum venetum L. flowers, and their innate immune-stimulating functions and working mechanisms were evaluated in RAW264.7 cells. Both the level of released nitric oxide(NO) and expression of inducible nitric oxide synthase(iNOS) m RNA were significantly enhanced in the RAW264.7 macrophages cells treated by Vp2a-Ⅱ and Vp3. Vp2a-Ⅱ(100–800 μg/m L) and Vp3(400 μg/mL) could significantly increase the phagocytic activity of RAW264.7 cells and the secretion and m RNA expression of TNF-α and IL-6 in a concentrationdependent manner through affecting mitogen-activated protein kinase(MAPK) activity and nuclear factor κB(NF-κB) nuclear translocation. Vp2a-Ⅱ might activate the MAPK signaling pathways and induce the nuclear translocation of NF-κB p65, whilst Vp3 likely activated the NF-κB and MAPK signaling pathways without influencing the p38 MAPK route.
基金the Independent Subject of Guangxi Key Laboratory of Medicinal Resources Protection and Genetic Improvement(No.KL2022ZZ01)Guangxi Innovation-Driven Development Project(No.GuiKe AA18242040)+3 种基金the National Key R&D Program of China(Nos.2019YFC1711000 and 2019YFC1711008)the Innovation Team Project of Guangxi Botanical Garden of Medicinal Plant(No.GuiYaoChuang2019002)the Innovation and Demonstration of Guangxi Academician Workstation(No.2021AV07007)Government Guided Local Science and Technology Development Project(No.GuiKeZY 20198018).
文摘Nasopharyngeal carcinoma(NPC)is the third most common malignancy with a high recurrence and metastasis rate in South China.Natural compounds extracted from traditional Chinese herbal medicines have been developed and utilized for the treatment of a variety of cancers with modest properties and slight side effects.Maackiain(MA)is a type of flavonoid that was first isolated from leguminous plants,and it has been reported to relieve various nervous system disorders and exert anti-allergic as well as antiinflammatory effects.In this study,we demonstrated that MA inhibited proliferation,arrested cell cycle and induced apoptosis in nasopharyngeal carcinoma CNE1 and CNE2 cells in vitro and in vivo.The expression of the related proteins associated with these processes were consistent with the above effects.Moreover,transcriptome sequencing and subsequent Western blot experiments revealed that inhibition of the MAPK/Ras pathway may be responsible to the anti-tumor effect of MA on NPC cells.Therefore,the effects of MA and an activator of this pathway,tertiary butylhydroquinone(TBHQ),alone or combination,were investigated.The results showed TBHQ neutralized the inhibitory effects of MA.These data suggest that MA exerts its anti-tumor effect by inhibiting the MAPK/Ras signaling pathway and it has the potential to become a treatment for patients with NPC.
文摘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.
基金supported by the National Natural Science Foundation of China(31972217 and 32072369)the Central Government Guides Local Science and Technology Development Projects,China(206Z6501G and 216Z6502G)the Research Project of Basic Scientific Research Business Fees in Provincial Universities of Hebei Province,China(KY2021043 and KY2021044)。
文摘Botrytis cinerea is a typical necrotrophic pathogenic fungus that causes severe diseases in a wide range of plant species, leading to significant economic losses. Our previous study showed that BcSDR1 positively regulates growth,development, and pathogenicity of B. cinerea. However, the regulation mechanism of BcSDR1 and the relationship between BcSDR1 and cAMP and MAPK signaling pathways are not well understood. In this study, transcriptome data showed that BcSDR1 is involved in glucose transmembrane transport, signal transduction, secondary metabolism, and other biological processes. BcSDR1 mutant(BCt41) showed remarkably weak sensitivity to cAMP and MAPK signaling pathways specific inhibitors, SQ22536 and U0126, and significantly decreased cAMP content. The key genes of cAMP and MAPK signaling pathways, BcGB1, BcBTP1, BcBOS1, BcRAS1, and BcBMP3 were significantly upregulated,whereas BcPLC1, BcBCG1, BcCDC4, BcSAK1, BcATF1, and BcBAP1 were significantly downregulated(P<0.05).BcSDR1 was obviously upregulated in BcBCG2, BcBCG3, BcPKA1, and BcPKAR RNA interference(RNAi) mutants, but significantly downregulated in BcPKA2, BcBMP1, and BcBMP3 RNAi mutants. Thus, BcBCG2, BcBCG3, BcPKA1, and BcPKAR negatively regulate BcSDR1 expression, whereas BcPKA2, BcBMP1, and BcBMP3 positively regulate BcSDR1expression.
基金funded by the National Natural Science Foundation of China(31901698)Young Elite Scientists Sponsorship Program by the China Association for Science and Technology(2019QNRC001)。
文摘Cyanidin-3-glucoside(C3G)is the most common anthocyanin in dark grains and berries and is a food functional factor to improve visual health.However,the mechanisms of C3G on blue light-induced retinal pigment epithelial(RPE)cell photooxidative damage needs further exploration.We investigated the effects of C3G on blue light-irradiated A2E-containing RPE cells and explored whether sphingolipid,mitogen-activated protein kinase(MAPK),and mitochondria-mediated pathways are involved in this mechanism.Blue light irradiation led to mitochondria and lysosome damage in RPE cells,whereas C3G preserved mitochondrial morphology and function and maintained the lysosomal integrity.C3G suppressed the phosphorylation of JNK and p38 MAPK and mitochondria-mediated pathways to inhibit RPE cell apoptosis.Lipidomics data showed that C3G protected RPE cells against blue light-induced lipid peroxidation and apoptosis by maintaining sphingolipids balance.C3G significantly inhibited ceramide(Cer d18:0/15:0,Cer d18:0/16:0 and Cer d18:0/18:0)accumulation and elevated galactosylceramide(GalCer d18:1/15:0 and GalCer d18:1/16:0)levels in the irradiated A2E-containing RPE cells.Furthermore,C3G attenuated cell membrane damage by increasing phosphatidylcholine and phosphatidylserine levels.C3G inhibited apoptosis and preserved the structure of mitochondria and lysosome by regulating sphingolipid signaling and suppression of MAPK activation in RPE cells.Thus,dietary supplementation of C3G prevents retinal photooxidative damage.
基金This study was supported by Modern Agricultural Industry Technology System-Peking Poultry Innovation Team(BAIC04–2021)the National Key R&D Program of China(2016YFD0700201).
文摘Background:Natural astaxanthin(ASTA)has strong antioxidant properties and has been widely used as a health product to improve human health.However,the effects of ASTA on the reproductive performance of aging roosters have been poorly studied.We aimed to investigate the effects of dietary ASTA on semen quality and antioxidant capacity in aging roosters and to explore the potential mechanism of semen quality change via antioxidation defense system.Methods:In the present study,9653-week-old Jinghong No.1 layer breeder roosters were fed a corn-soybean meal basal diet containing 0,25,50,or 100 mg/kg ASTA for 6 weeks.Results:Semen quality in the ASTA groups remarkably improved than that in the control group,and antioxidant activities,the abilities to scavenge hydroxyl radicals and superoxide anions,increased gradually with ASTA addition(P<0.05).In addition,the mRNA levels of antioxidant enzymes as well as the mRNA and protein levels of the mitogen-activated protein kinase(MAPK)and nuclear factor-erythroid 2-related factor 2(Nrf2)were markedly increased in the 50-100 mg/kg ASTA group(P<0.05).Conclusions:Collectively,these results demonstrate that dietary ASTA may improve semen quality by increasing antioxidant enzyme activities and the ability to scavenge hydroxyl radicals,which may be related to upregulation of the MAPK/Nrf2 pathway.
基金supported by the CEMB-TWAS Postgraduate Fellowship(FR number 3240286682,2015)granted to Mr.Koloko Brice Landry
文摘Objective:To evaluate the antiviral activity and phytochemicals of selected plant extracts and their effect on the mitogen-activated protein kinase(MAPK)signaling pathway modulated by hepatitis C virus(HCV)nonstructural protein 5 A(NS5A).Methods:A total of ten plant extracts were initially screened for their toxicities against Hep G2 cells.The non-toxic plants were tested for their inhibitory effect on the expression of HCV NS5A at both m RNA and protein levels using real-time PCR and Western blotting assays,respectively.The differential expression of the genes associated with MAPK pathway in the presence of NS5A gene and plant extract was measured through real-time PCR.Subsequently,the identification of secondary metabolites was carried out by phytochemical and HPLC analysis.Results:The phytochemical profiling of Berberis lyceum revealed the presence of alkaloids,phenols,saponins,tannins,flavonoids,carbohydrates,terpenoids,steroids,and glycosides.Similarly,quercetin,myricetin,gallic acid,caffeic acid,and ferulic acid were identified through HPLC analysis.The methanolic extract of Berberis lyceum strongly inhibited HCV RNA replication with an IC50 of 11.44μg/m L.RT-PCR and Western blotting assays showed that the extract reduced the expression of HCV NS5A in a dosedependent manner.Berberis lyceum extract also attenuated NS5A-induced dysregulation of the MAPK signaling pathway.Conclusions:Our findings suggest that Berberis lyceum extract strongly inhibits HCV propagation by reducing HCV NS5A-induced perturbation of MAPK signaling.
