BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicate...BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicated a potential link between CSF3R expression and the immunosuppressive receptor leukocyte immunoglobulin-like receptor B2(LILRB2)in GC.We hypothesized that CSF3/CSF3R may regulate LILRB2 and its ligands,angiopoietin-like protein 2(ANGPTL2)and human leukocyte antigen-G(HLA-G),contributing to immunosuppression.AIM To investigate the relationship between CSF3/CSF3R and LILRB2,as well as its ligands ANGPTL2 and HLA-G,in GC.METHODS Transcriptome sequencing data from The Cancer Genome Atlas were analyzed,stratifying patients by CSF3R expression.Differentially expressed genes and immune checkpoints were evaluated.Immunohistochemistry(IHC)was performed on GC tissues.Correlation analyses of CSF3R,LILRB2,ANGPTL2,and HLA-G were conducted using The Cancer Genome Atlas data and IHC results.GC cells were treated with CSF3,and expression levels of LILRB2,ANGPTL2,and HLA-G were measured by quantitative reverse transcriptase-polymerase chain reaction and western blotting.RESULTS Among 122 upregulated genes in high CSF3R expression groups,LILRB2 showed the most significant increase.IHC results indicated high expression of LILRB2(63.0%),ANGPTL2(56.5%),and HLA-G(73.9%)in GC tissues.Strong positive correlations existed between CSF3R and LILRB2,ANGPTL2,and HLA-G mRNA levels(P<0.001).IHC confirmed positive correlations between CSF3R and LILRB2(P<0.001),and HLA-G(P=0.010),but not ANGPTL2(P>0.05).CSF3 increased LILRB2,ANGPTL2,and HLA-G expression in GC cells.Heterogeneous nuclear ribonucleoprotein H1 modulation significantly altered their expression,impacting CSF3’s regulatory effects.CONCLUSION The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands,with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role.展开更多
Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanism...Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanisms underlying VM in OSCC.Methods:Bioinformatics analysis was performed utilizing single-cell RNA-seq,bulk RNA-seq,and histone H3 lysine 27 acetylation(H3K27ac)Chromatin Immunoprecipitation(ChIP)-seq data obtained from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.ChIP-qPCR was used to validate the binding of ETS transcription factor ELK4(ELK4)to the dihydrofolate reductase(DHFR)enhancer.In vitro VM formation and invasion of OSCC cells were assessed using Matrigel-based tube formation and Transwell assays,respectively.Results:Elevated expression of VM-related genes predicts unfavorable prognosis in OSCC patients.High-dimensional weighted gene co-expression network analysis(hdWGCNA)identified epithelial subcluster C4 as most strongly associated with VM and metastasis.Three co-expression modules within this subcluster exhibited significant positive correlations with both phenotypic traits.Among the 30 eigengenes from the three modules,DHFR emerged as a key regulator of VM and metastasis.Knockdown or inhibition of DHFR significantly suppressed VM formation and invasion in OSCC cells.Mechanistically,ELK4 activated DHFR transcription through direct binding to its enhancer.DHFR overexpression rescued VM and invasion impairment induced by ELK4 knockdown.Conclusion:DHFR was a pivotal enhancer-regulated gene driving VM and metastasis in OSCC.ELK4 directly binds to DHFR enhancer regions to activate its transcription,thereby promoting these malignant phenotypes.These findings identified the ELK4/DHFR axis as a promising therapeutic target for anti-angiogenic intervention in OSCC.展开更多
BACKGROUND Colorectal cancer(CRC)has become the second most deadly malignancy in the world,and the exploration of screening markers and precise therapeutic targets is urgent.Our previous research identified leukocyte ...BACKGROUND Colorectal cancer(CRC)has become the second most deadly malignancy in the world,and the exploration of screening markers and precise therapeutic targets is urgent.Our previous research identified leukocyte immunoglobulin-like receptor B2(LILRB2)protein as a characteristic protein of CRC,but the association between LILRB2 expression and clinicopathological features,the internal mechanism related to CRC progression,and screening diagnostic efficacy are not clear.Therefore,we hypothesized that LILRB2 is significantly highly expressed in CRC tissues,correlated with advanced stage and a poor prognosis,and could be used as a therapeutic target and potential screening biomarker for CRC.AIM To explore whether LILRB2 can be used as a potential therapeutic target and noninvasive screening biomarker for CRC.METHODS Patients who underwent radical surgery for CRC at China-Japan Friendship Hospital between February 2021 and October 2022 were included.Cancer and paracancerous tissues were collected to verify LILRB2 expression,and the association between LILRB2 expression and clinicopathological features was analysed.Serum was collected from CRC patients,adenoma patients and healthy controls during the same period to assess the diagnostic value of LILRB2 as a noninvasive screening biomarker,and its diagnostic value was further compared with that of the traditional markers carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9).RESULTS A total of 58 CRC patients were included,and LILRB2 protein was significantly overexpressed in cancer tissues compared with paracancerous tissues(P<0.001).Angiopoietin-like protein 2(ANGPTL2)protein,as the ligand of LILRB2,was synergistically overexpressed in CRC tissues(P<0.001),and overexpression of LILRB2 and ANGPTL2 protein was significantly correlated with poor to moderate differentiation,vascular involvement,lymph node metastasis,distant metastasis,advanced tumor-node-metastasis stage and a poor prognosis(P<0.05),which suggested that LILRB2 and ANGPTL2 are closely associated with CRC progression.In addition,serum LILRB2 concentrations increased stepwise in healthy individuals,adenoma patients and CRC patients with statistically significant differences.The sensitivity of serum LILRB2 for the diagnosis of CRC was 89.74%,the specificity was 88.89%,the area under the curve was 0.95,and the diagnostic efficacy was better than that of conventional CEA and CA19-9.CONCLUSION LILRB2 protein can be used as a potential novel therapeutic target and noninvasive screening biomarker for CRC,which is beneficial for early screening and precise treatment.展开更多
Killer cell immunoglobulin-like receptors （KIRs） which are mainly expressed on natural killer （NK） cells are implicated in many virus infections. However, it is unclear whether or not KIRs are associated with susc...Killer cell immunoglobulin-like receptors （KIRs） which are mainly expressed on natural killer （NK） cells are implicated in many virus infections. However, it is unclear whether or not KIRs are associated with susceptibility to Epstein-Barr virus （EBV） infection related diseases. Therefore, the purpose of our study was to investigate possible correlation between polymorphisms of KIR genes and infectious mononucleosis （IM）/EBV-associated hemophagocytic Iymphohistiocytosis （EBV-HLH）. The polymorphisms of KIR genes were detected by polymerase chain reaction with sequence-specific primers （PCR-SSP）. The results would contribute to clarify the association of KIRs with EBV induced diseases, and provide new insights into the role of NK cells and innate immune response against viral infections and/or subsequent progression.展开更多
Many mechanisms have been proposed to explain the hypothetical state of hepatic tolerance,which is described by eventual imbalances or deregulation in the balance of cytokines,mediators,effectors,and regulatory cells ...Many mechanisms have been proposed to explain the hypothetical state of hepatic tolerance,which is described by eventual imbalances or deregulation in the balance of cytokines,mediators,effectors,and regulatory cells in the complex milieu of the liver.In this section,we will comment on the importance of donorspecific anti-human leukocyte antigen(HLA)antibodies(DSA)as well as the compatibility and pairings of HLA and killer-cell immunoglobulin-like receptor(KIR)genotypes in the evolution of liver transplantation.Thus,HLA compatibility,viral infections,and HLA-C/KIR combinations have all been linked to liver transplant rejection and survival.There have been reports of increased risk of acute and chronic rejection with ductopenia,faster graft fibrosis,biliary problems,poorer survival,and even de novo autoimmune hepatitis when DSAs are present in the recipient.Higher mean fluorescence intensity(MFI)values of the DSAs and smaller graft size were associated with poorer patient outcomes,implying that high-risk patients with preformed DSAs should be considered for selecting the graft placed and desensitization methods,according to the investigators.Similarly,in a combined kidney-liver transplant,a pretransplant with a visible expression of several DSAs revealed that these antibodies were resistant to treatment.The renal graft was lost owing to antibody-mediated rejection(AMR).The HLA antigens expressed by the transplanted liver graft influenced antibody elimination.Pathologists are increasingly diagnosing AMR in liver transplants,and desensitization therapy has even been employed in situations of AMR,particularly in patients with DSAs in kidney-hepatic transplants and high-class II MFI due to Luminex.In conclusion,after revealing the negative impacts of DSAs with high MFI,pretransplant virtual crossmatch techniques may be appropriate to improve evolution;however,they may extend cold ischemia periods by requiring the donor to be typed.展开更多
According to the latest global cancer statistics,colorectal cancer(CRC)has emerged as the third most prevalent malignant tumor across the globe.In recent decades,the medical field has implemented several levels of CRC...According to the latest global cancer statistics,colorectal cancer(CRC)has emerged as the third most prevalent malignant tumor across the globe.In recent decades,the medical field has implemented several levels of CRC screening tests,encompassing fecal tests,endoscopic examinations,radiological examinations and blood tests.Previous studies have shown that leukocyte immunoglobulin-like receptor B2(LILRB2)is involved in inhibiting immune cell function,immune evasion,and promoting tumor progression in acute myeloid leukemia and nonsmall cell lung cancer.However,its interaction with CRC has not been reported yet.Recently,a study published in the World Journal of Gastroenterology revealed that LILRB2 and its ligand,angiopoietin-like protein 2,are markedly overexpressed in CRC.This overexpression is closely linked to tumor progression and is indicative of a poor prognosis.The study highlights the potential of utilizing the concentration of LILRB2 in serum as a promising biomarker for tumors.However,there is still room for discussion regarding the data processing and analysis in this research.展开更多
Regenerative capacity is weak after central nervous system injury because of the absence of an enhancing microenvironment and presence of an inhibitory microenvironment for neuronal and axonal repair. In addition to t...Regenerative capacity is weak after central nervous system injury because of the absence of an enhancing microenvironment and presence of an inhibitory microenvironment for neuronal and axonal repair. In addition to the Nogo receptor（Ng R）, the paired immunoglobulin-like receptor B（Pir B） is a recently discovered coreceptor of Nogo, myelin-associated glycoprotein, and myelin oligodendrocyte glycoprotein. Concurrent blocking of Ng R and Pir B almost completely eliminates the inhibitory effect of myelin-associated inhibitory molecules on axonal regeneration. Pir B participates in a key pathological process of the nervous system, specifically axonal regeneration inhibition. Pir B is an inhibitory receptor similar to Ng R, but their effects are not identical. This study summarizes the structure, distribution, relationship with common nervous system diseases, and known mechanisms of Pir B, and concludes that Pir B is also distributed in cells of the immune and hematopoietic systems. Further investigations are needed to determine if immunomodulation and blood cell migration involve inhibition of axonal regeneration.展开更多
Paired immunoglobulin-like receptor B（Pir B） is a functional receptor of myelin-associated inhibitors for axonal regeneration and synaptic plasticity in the central nervous system, and thus suppresses nerve regenera...Paired immunoglobulin-like receptor B（Pir B） is a functional receptor of myelin-associated inhibitors for axonal regeneration and synaptic plasticity in the central nervous system, and thus suppresses nerve regeneration. The regulatory effect of Pir B on injured nerves has received a lot of attention. To better understand nerve regeneration inability after spinal cord injury, this study aimed to investigate the distribution of Pir B（via immunofluorescence） in the central nervous system and peripheral nervous system 10 days after injury. Immunoreactivity for Pir B increased in the dorsal root ganglia, sciatic nerves, and spinal cord segments. In the dorsal root ganglia and sciatic nerves, Pir B was mainly distributed along neuronal and axonal membranes. Pir B was found to exhibit a diffuse, intricate distribution in the dorsal and ventral regions. Immunoreactivity for Pir B was enhanced in some cortical neurons located in the bilateral precentral gyri. Overall, the findings suggest a pattern of Pir B immunoreactivity in the nervous system after unilateral spinal transection injury, and also indicate that Pir B may suppress repair after injury.展开更多
The current study investigated correlations between the expression of leucine-rich repeats and immunoglobulin-like domain 1 （LRIG1） and antioxidant enzymes and related proteins, including manganese superoxide dismut...The current study investigated correlations between the expression of leucine-rich repeats and immunoglobulin-like domain 1 （LRIG1） and antioxidant enzymes and related proteins, including manganese superoxide dismutase, glutamate cysteine ligase catalytic or regulatory subunit, thioredoxin and thioredoxin reductase, in both human ependymoma and oligodendroglioma. Results revealed that the cytoplasmic expression of LRIG1 was associated with expression of glutamate cysteine ligase catalytic subunit in the human ependymoma, while the nuclear expression of LRIG1 was associated with expression of thioredoxin reductase. In human oligodendroglioma, the cytoplasmic expression of LRIG1 was associated with expression of the glutamate cysteine ligase catalytic subunit. Both the nuclear and perinuclear expressions of LRIG1 were associated with expression of glutamate cysteine ligase regulatory subunit. These results indicated that several antioxidant enzymes and related proteins contributed to LRIG1 expression, and that these may participate in the antioxidation of the cells.展开更多
Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecu...Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.展开更多
Tomato is an important economic crop all over the world.Volatile flavors in tomato fruit are key factors influencing consumer liking and commercial quality.However,the regulatory mechanism controlling the volatile fla...Tomato is an important economic crop all over the world.Volatile flavors in tomato fruit are key factors influencing consumer liking and commercial quality.However,the regulatory mechanism controlling the volatile flavors of tomatoes is still not clear.Here,we integrated the metabolome and transcriptome of the volatile flavors in tomato fruit to explore the regulatory mechanism of volatile flavor formation,using wild and cultivated tomatoes with significant differences in flavors.A total of 35 volatile flavor compounds were identified,based on the solid phase microextraction-gas chromatography-mass spectrometry(SPME-GC-MS).The content of the volatiles,affecting fruit flavor,significantly increased in the transition from breaker to red ripe fruit stage.Moreover,the total content of the volatiles in wild tomatoes was much higher than that in the cultivated tomatoes.The content variations of all volatile flavors were clustered into 10 groups by hierarchical cluster and Pearson coefficient correlation(PCC)analysis.The fruit transcriptome was also patterned into 10 groups,with significant variations both from the mature green to breaker fruit stage and from the breaker to red ripe fruit stage.Combining the metabolome and the transcriptome of the same developmental stage of fruits by co-expression analysis,we found that the expression level of 1182 genes was highly correlated with the content of volatile flavor compounds,thereby constructing two regulatory pathways of important volatile flavors.One pathway is tetrahydrothiazolidine N-hydroxylase(SlTNH1)-dependent,which is regulated by two transcription factors(TFs)from the bHLH and AP2/ERF families,controlling the synthesis of 2-isobutylthiazole in amino acid metabolism.The other is lipoxygenase(Sl LOX)-dependent,which is regulated by one TF from the HD-Zip family,controlling the synthesis of hexanal and(Z)-2-heptenal in fatty acid metabolism.Dual-luciferase assay confirmed the binding of b HLH and AP2/ERF to their structural genes.The findings of this study provide new insights into volatile flavor formation in tomato fruit,which can be useful for tomato flavor improvement.展开更多
The NAC(NAM,ATAF1/2,and CUC2)is a defense-associated transcription factor(TF)family that positively regulates defense responses to pathogen infection.TaNAC069 positively regulates resistance in wheat to Puccinia triti...The NAC(NAM,ATAF1/2,and CUC2)is a defense-associated transcription factor(TF)family that positively regulates defense responses to pathogen infection.TaNAC069 positively regulates resistance in wheat to Puccinia triticina(Pt).However,the molecular mechanism of its interaction with a Pt effector is not clear.We found that Pt effector Pt-1234 interacts with TaNAC069 to subvert host immunity during Pt infection.Quantitative real-time PCR analysis showed that expression of Pt-1234 was significantly upregulated during the early stage of Pt infection.Protein-mediated cell death assays in wheat showed that the Pt-1234 protein was unable to induce cell death in wheat near-isogenic lines carrying different leaf rust resistance genes,whereas it suppressed BAX-induced cell death in leaves of Nicotiana benthamiana.Silencing of Pt-1234 by host-induced gene silencing(HIGS)significantly reduced the virulence of Pt in the susceptible wheat variety Thatcher.The C subdomain of TaNAC069 was responsible for its interaction with Pt-1234,and the E subdomain was required for TaNAC069-mediated defense responses to Pt in planta.These findings indicate that Pt utilizes Pt-1234 to interact with wheat transcription factor TaNAC069 through its C subdomain,thereby modulating wheat immunity.展开更多
Tomato(Solanum lycopersicum)is an important fruit and vegetable crop in worldwide.The fertility of tomato reproductive organs can be dramatically decreased when ambient temperatures rise above 35°C,reducing tomat...Tomato(Solanum lycopersicum)is an important fruit and vegetable crop in worldwide.The fertility of tomato reproductive organs can be dramatically decreased when ambient temperatures rise above 35°C,reducing tomato fruit yield.It is necessary to identify transcription factors(TFs)and target genes involved in heat stress response(HSR)signaling cascades in tomato flower buds to improve tomato plant thermotolerance.In this study,we profiled genes expressed in three developmental stages of tomato flower buds.Red and turquoise modules for heat stress(HS)were identified through gene co-expression network analysis,and the genes within these modules were enriched in HS-related pathways.By focusing on the TFs in the two modules,we identified several novel HSR-related TFs,including SlWRKY75,SlMYB117,and SlNAM.Furthermore,homology analysis illustrated a conserved signaling cascade in tomato.Lastly,we identified and experimentally validated four HSF-regulated genes,namely SlGrpE,SlERDJ3A,SlTIL,and SlPOM1,that likely modulate thermotolerance in plants.These results provide a high-resolution atlas of gene expression during tomato flower bud development under HS conditions,which is a valuable resource for uncovering potential regulatory networks associated with the HSR in tomato.展开更多
The emergence of novel phytopathogens and the accelerated spread of plant diseases to new regions,driven by global climate change,constitute significant threats to agricultural resources.Rice,a major tropical staple c...The emergence of novel phytopathogens and the accelerated spread of plant diseases to new regions,driven by global climate change,constitute significant threats to agricultural resources.Rice,a major tropical staple crucial for global food security,possesses six transcription factor superfamilies-AP2/ERF,bHLH,bZIP,MYB,NAC,and WRKY-that function in innate immunity against pathogens.We review their biological functions and regulatory mechanisms in rice immunity.展开更多
Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant...Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.展开更多
BACKGROUND Diabetic retinopathy(DR)is a major microvascular complication of diabetes mellitus,leading to significant visual impairment and blindness among adults.Current treatment options are limited,making it essenti...BACKGROUND Diabetic retinopathy(DR)is a major microvascular complication of diabetes mellitus,leading to significant visual impairment and blindness among adults.Current treatment options are limited,making it essential to explore novel therapeutic strategies.Curcumol,a sesquiterpenoid derived from traditional Chinese medicine,has shown anti-inflammatory and anti-cancer properties,but its potential role in DR remains unclear.AIM To investigate the therapeutic effects of curcumol on the progression of DR and to elucidate the underlying molecular mechanisms,particularly its impact on the fat mass and obesity-associated(FTO)protein and the long non-coding RNA(lncRNA)MAF transcription factor G antisense RNA 1(MAFG-AS1).METHODS A streptozotocin-induced mouse model of DR was established,followed by treatment with curcumol.Retinal damage and inflammation were evaluated through histological analysis and molecular assays.Human retinal vascular endothelial cells were exposed to high glucose conditions to simulate diabetic environments in vitro.Cell proliferation,migration,and inflammation markers were assessed in curcumoltreated cells.LncRNA microarray analysis identified key molecules regulated by curcumol,and further experiments were conducted to confirm the involvement of FTO and MAFG-AS1 in the progression of DR.RESULTS Curcumol treatment significantly reduced blood glucose levels and alleviated retinal damage in streptozotocininduced DR mouse models.In high-glucose-treated human retinal vascular endothelial cells,curcumol inhibited cell proliferation,migration,and inflammatory responses.LncRNA microarray analysis identified MAFG-AS1 as the most upregulated lncRNA following curcumol treatment.Mechanistically,FTO demethylated MAFG-AS1,stabilizing its expression.Rescue experiments demonstrated that the protective effects of curcumol against DR were mediated through the FTO/MAFG-AS1 signaling pathway.CONCLUSION Curcumol ameliorates the progression of DR by modulating the FTO/MAFG-AS1 axis,providing a novel therapeutic pathway for the treatment of DR.These findings suggest that curcumol-based therapies could offer a promising alternative for managing this debilitating complication of diabetes.展开更多
Objective:Polycystic ovary syndrome(PCOS)is a common endocrine disorder that affects women’s health.This study aims to investigate gene and transcription factor(TF)expression differences between PCOS patients and hea...Objective:Polycystic ovary syndrome(PCOS)is a common endocrine disorder that affects women’s health.This study aims to investigate gene and transcription factor(TF)expression differences between PCOS patients and healthy individuals using bioinformatics approaches,and to verify the function of key transcription factors,with the goal of providing new insights into the pathogenesis of PCOS.Methods:Differentially expressed genes(DEGs)and differentially expressed transcription factors(DETFs)between PCOS patients and controls were identified from the RNA sequencing dataset GSE168404 using bioinformatics methods.Functional enrichment analysis was performed using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.The expression and function of core transcription factors were further validated in ovarian tissues of PCOS model mice and control mice using Western blotting and reverse transcription quantitative polymerase chain reaction(RTqPCR).Results:A total of 332 DEGs were identified between PCOS patients and controls,including 259 upregulated and 73 downregulated genes in the PCOS group.19 DETFs were further screened,of which 16 were upregulated and 3 were downregulated in PCOS.The upregulated DETFs(including TFCP2L1,DACH1,ESR2,AFF3,SMAD9,ZNF331,HOPX,ATOH8,HIF3α,DPF3,HOXC4,HES1,ID1,JDP2,SOX4,and ID3)were primarily associated with lipid metabolism,development,and cell adhesion.Protein and mRNA expression analysis in PCOS model mice revealed significantly decreased levels of hypoxia-inducible factor(HIF)1αand HIF2α,and significantly increased expression of HIF3αcompared to control mice(all P<0.001).Conclusion:Significant differences in gene and TF expression exist between PCOS patients and healthy individuals.HIF-3αmay play a crucial role in PCOS and could serve as a novel biomarker for diagnosis and a potential therapeutic target.展开更多
Loss-of-function variants of low-density lipoprotein receptor-related protein 5(LRP5)can lead to reduced bone formation,culminating in diminished bone mass.Our previous study reported transcription factor osterix(SP7)...Loss-of-function variants of low-density lipoprotein receptor-related protein 5(LRP5)can lead to reduced bone formation,culminating in diminished bone mass.Our previous study reported transcription factor osterix(SP7)-binding sites on the LRP5 promoter and its pivotal role in upregulating LRP5 expression during implant osseointegration.However,the potential role of SP7 in ameliorating LRP5-dependent osteoporosis remained unknown.In this study,we used mice with a conditional knockout(c KO)of LRP5 in mature osteoblasts,which presented decreased osteogenesis.The in vitro experimental results showed that SP7 could promote LRP5 expression,thereby upregulating the osteogenic markers such as alkaline phosphatase(ALP),Runt-related transcription factor 2(Runx2),andβ-catenin(P<0.05).For the in vivo experiment,the SP7 overexpression virus was injected into a bone defect model of LRP5 c KO mice,resulting in increased bone mineral density(BMD)(P<0.001)and volumetric density(bone volume(BV)/total volume(TV))(P<0.001),and decreased trabecular separation(Tb.Sp)(P<0.05).These data suggested that SP7 could ameliorate bone defect healing in LRP5 c KO mice.Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.展开更多
bHLH transcription factors,widely exist in various plants,and are vital for the growth and development of these plants.Among them,many have been implicated in anthocyanin biosynthesis across various plants.In the pres...bHLH transcription factors,widely exist in various plants,and are vital for the growth and development of these plants.Among them,many have been implicated in anthocyanin biosynthesis across various plants.In the present study,a PdbHLH57 gene,belonging to the bHLH IIIf group,was characterized,which was isolated and cloned from the colored-leaf poplar‘Zhongshancaiyun’(ZSCY).The cDNA sequence of PdbHLH57 was 1887 base pairs,and the protein encoded by PdbHLH57 had 628 amino acids,the isoelectric point and molecular weight of which were 6.26 and 69.75 kDa,respectively.Through bioinformatics analysis,PdbHLH57 has been classified into the IIIf bHLH subgroup,with many members of this subgroup known to participate in anthocyanin biosynthesis.The subcellular localization analysis conducted in the leaf protoplasts of‘ZSCY’revealed that the PdbHLH57 protein is specifically localized in the nucleus.The transcription activation analysis was also conducted,and the results showed that the PdbHLH57 protein had self-transcription activation.To better explore the functions of the PdbHLH57 protein,two parts of this protein(PdbHLH57-1,PdbHLH57-2)were split to detect their transcriptional activation activity.The results indicated that PdbHLH57-1(1-433aa)had self-transcription activation,and PdbHLH57-2(433-628aa)had no transcription activation.The expression of PdbHLH57 peaked in June during different developmental stages in‘ZSCY’,and it was most highly expressed in the phloem among various tissues.These findings offer a basis for understanding the role of PdbHLH57 in colored-leaf poplar.展开更多
Myeloblastosis(MYB)transcription factors(TFs)are evolutionarily conserved regulatory proteins that are crucial for plantgrowth,development,secondarymetabolism,andstress adaptation.Recent studieshavehighlighted their c...Myeloblastosis(MYB)transcription factors(TFs)are evolutionarily conserved regulatory proteins that are crucial for plantgrowth,development,secondarymetabolism,andstress adaptation.Recent studieshavehighlighted their crucial role in coordinating growth–defense trade-offs through transcriptional regulation of key biosynthetic and stress-response genes.Despite extensive functional characterization in model plants such as Arabidopsis thaliana,systematically evaluating the broader functional landscape of MYB TFs across diverse species and contexts remains necessary.This systematic review integrates results from 24 peer-reviewed studies sourced from Scopus and Web of Science,focusing on the functional diversity of MYB TFs,particularly in relation to abiotic stress tolerance,metabolic regulation,and plant developmental processes.Advances in genomic technologies,such as transcriptomics,genome editing,and comparative phylogenetics,have considerably enhanced our understanding of MYB-mediated regulatory mechanisms.These tools have facilitated the identification and functional characterization of MYB genes across model and non-model plant species.Key findings underscore the multifaceted roles of MYB TFs in enhancing stress resilience,modulating anthocyanin and flavonoid biosynthesis,and contributing to yield-related traits,thereby highlighting their potential applications in crop improvement and sustainable agriculture.However,critical gaps exist in understanding MYB interactions within complex regulatory networks,particularly in underrepresented plant species and ecological contexts.This review consolidates current knowledge as well as identifies research gaps and proposes future directions to advance the understanding and application of MYB TFs.The insights derived from this study underscore their transformative potential in addressing global challenges including food security and climate resilience through innovative agricultural practices.展开更多
基金Supported by Hebei Province Medical Science Research Project Plan,No.20230755.
文摘BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicated a potential link between CSF3R expression and the immunosuppressive receptor leukocyte immunoglobulin-like receptor B2(LILRB2)in GC.We hypothesized that CSF3/CSF3R may regulate LILRB2 and its ligands,angiopoietin-like protein 2(ANGPTL2)and human leukocyte antigen-G(HLA-G),contributing to immunosuppression.AIM To investigate the relationship between CSF3/CSF3R and LILRB2,as well as its ligands ANGPTL2 and HLA-G,in GC.METHODS Transcriptome sequencing data from The Cancer Genome Atlas were analyzed,stratifying patients by CSF3R expression.Differentially expressed genes and immune checkpoints were evaluated.Immunohistochemistry(IHC)was performed on GC tissues.Correlation analyses of CSF3R,LILRB2,ANGPTL2,and HLA-G were conducted using The Cancer Genome Atlas data and IHC results.GC cells were treated with CSF3,and expression levels of LILRB2,ANGPTL2,and HLA-G were measured by quantitative reverse transcriptase-polymerase chain reaction and western blotting.RESULTS Among 122 upregulated genes in high CSF3R expression groups,LILRB2 showed the most significant increase.IHC results indicated high expression of LILRB2(63.0%),ANGPTL2(56.5%),and HLA-G(73.9%)in GC tissues.Strong positive correlations existed between CSF3R and LILRB2,ANGPTL2,and HLA-G mRNA levels(P<0.001).IHC confirmed positive correlations between CSF3R and LILRB2(P<0.001),and HLA-G(P=0.010),but not ANGPTL2(P>0.05).CSF3 increased LILRB2,ANGPTL2,and HLA-G expression in GC cells.Heterogeneous nuclear ribonucleoprotein H1 modulation significantly altered their expression,impacting CSF3’s regulatory effects.CONCLUSION The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands,with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role.
基金supported by Hebei Natural Science Foundation(H2024206476)Medical Science Research Project of Hebei(20240101).
文摘Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanisms underlying VM in OSCC.Methods:Bioinformatics analysis was performed utilizing single-cell RNA-seq,bulk RNA-seq,and histone H3 lysine 27 acetylation(H3K27ac)Chromatin Immunoprecipitation(ChIP)-seq data obtained from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.ChIP-qPCR was used to validate the binding of ETS transcription factor ELK4(ELK4)to the dihydrofolate reductase(DHFR)enhancer.In vitro VM formation and invasion of OSCC cells were assessed using Matrigel-based tube formation and Transwell assays,respectively.Results:Elevated expression of VM-related genes predicts unfavorable prognosis in OSCC patients.High-dimensional weighted gene co-expression network analysis(hdWGCNA)identified epithelial subcluster C4 as most strongly associated with VM and metastasis.Three co-expression modules within this subcluster exhibited significant positive correlations with both phenotypic traits.Among the 30 eigengenes from the three modules,DHFR emerged as a key regulator of VM and metastasis.Knockdown or inhibition of DHFR significantly suppressed VM formation and invasion in OSCC cells.Mechanistically,ELK4 activated DHFR transcription through direct binding to its enhancer.DHFR overexpression rescued VM and invasion impairment induced by ELK4 knockdown.Conclusion:DHFR was a pivotal enhancer-regulated gene driving VM and metastasis in OSCC.ELK4 directly binds to DHFR enhancer regions to activate its transcription,thereby promoting these malignant phenotypes.These findings identified the ELK4/DHFR axis as a promising therapeutic target for anti-angiogenic intervention in OSCC.
基金the National Key Development Plan for Precision Medicine Research,No.2017YFC0910002.
文摘BACKGROUND Colorectal cancer(CRC)has become the second most deadly malignancy in the world,and the exploration of screening markers and precise therapeutic targets is urgent.Our previous research identified leukocyte immunoglobulin-like receptor B2(LILRB2)protein as a characteristic protein of CRC,but the association between LILRB2 expression and clinicopathological features,the internal mechanism related to CRC progression,and screening diagnostic efficacy are not clear.Therefore,we hypothesized that LILRB2 is significantly highly expressed in CRC tissues,correlated with advanced stage and a poor prognosis,and could be used as a therapeutic target and potential screening biomarker for CRC.AIM To explore whether LILRB2 can be used as a potential therapeutic target and noninvasive screening biomarker for CRC.METHODS Patients who underwent radical surgery for CRC at China-Japan Friendship Hospital between February 2021 and October 2022 were included.Cancer and paracancerous tissues were collected to verify LILRB2 expression,and the association between LILRB2 expression and clinicopathological features was analysed.Serum was collected from CRC patients,adenoma patients and healthy controls during the same period to assess the diagnostic value of LILRB2 as a noninvasive screening biomarker,and its diagnostic value was further compared with that of the traditional markers carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9).RESULTS A total of 58 CRC patients were included,and LILRB2 protein was significantly overexpressed in cancer tissues compared with paracancerous tissues(P<0.001).Angiopoietin-like protein 2(ANGPTL2)protein,as the ligand of LILRB2,was synergistically overexpressed in CRC tissues(P<0.001),and overexpression of LILRB2 and ANGPTL2 protein was significantly correlated with poor to moderate differentiation,vascular involvement,lymph node metastasis,distant metastasis,advanced tumor-node-metastasis stage and a poor prognosis(P<0.05),which suggested that LILRB2 and ANGPTL2 are closely associated with CRC progression.In addition,serum LILRB2 concentrations increased stepwise in healthy individuals,adenoma patients and CRC patients with statistically significant differences.The sensitivity of serum LILRB2 for the diagnosis of CRC was 89.74%,the specificity was 88.89%,the area under the curve was 0.95,and the diagnostic efficacy was better than that of conventional CEA and CA19-9.CONCLUSION LILRB2 protein can be used as a potential novel therapeutic target and noninvasive screening biomarker for CRC,which is beneficial for early screening and precise treatment.
基金supported by grants from Chengdu Scientific and Technologic Bureau(No.11DXYB086JH-027)the research funds from the University Program for Changjiang Scholars and Innovative-Research Team(No.IRT0935)
文摘Killer cell immunoglobulin-like receptors （KIRs） which are mainly expressed on natural killer （NK） cells are implicated in many virus infections. However, it is unclear whether or not KIRs are associated with susceptibility to Epstein-Barr virus （EBV） infection related diseases. Therefore, the purpose of our study was to investigate possible correlation between polymorphisms of KIR genes and infectious mononucleosis （IM）/EBV-associated hemophagocytic Iymphohistiocytosis （EBV-HLH）. The polymorphisms of KIR genes were detected by polymerase chain reaction with sequence-specific primers （PCR-SSP）. The results would contribute to clarify the association of KIRs with EBV induced diseases, and provide new insights into the role of NK cells and innate immune response against viral infections and/or subsequent progression.
基金Instituto de Salud Carlos III,Spanish Ministry of Economy and Competitiveness,No.PI15/01370 and P19/01194and the European Union with the European Fund of Regional Development with the principle of“A manner to build Europe”.
文摘Many mechanisms have been proposed to explain the hypothetical state of hepatic tolerance,which is described by eventual imbalances or deregulation in the balance of cytokines,mediators,effectors,and regulatory cells in the complex milieu of the liver.In this section,we will comment on the importance of donorspecific anti-human leukocyte antigen(HLA)antibodies(DSA)as well as the compatibility and pairings of HLA and killer-cell immunoglobulin-like receptor(KIR)genotypes in the evolution of liver transplantation.Thus,HLA compatibility,viral infections,and HLA-C/KIR combinations have all been linked to liver transplant rejection and survival.There have been reports of increased risk of acute and chronic rejection with ductopenia,faster graft fibrosis,biliary problems,poorer survival,and even de novo autoimmune hepatitis when DSAs are present in the recipient.Higher mean fluorescence intensity(MFI)values of the DSAs and smaller graft size were associated with poorer patient outcomes,implying that high-risk patients with preformed DSAs should be considered for selecting the graft placed and desensitization methods,according to the investigators.Similarly,in a combined kidney-liver transplant,a pretransplant with a visible expression of several DSAs revealed that these antibodies were resistant to treatment.The renal graft was lost owing to antibody-mediated rejection(AMR).The HLA antigens expressed by the transplanted liver graft influenced antibody elimination.Pathologists are increasingly diagnosing AMR in liver transplants,and desensitization therapy has even been employed in situations of AMR,particularly in patients with DSAs in kidney-hepatic transplants and high-class II MFI due to Luminex.In conclusion,after revealing the negative impacts of DSAs with high MFI,pretransplant virtual crossmatch techniques may be appropriate to improve evolution;however,they may extend cold ischemia periods by requiring the donor to be typed.
文摘According to the latest global cancer statistics,colorectal cancer(CRC)has emerged as the third most prevalent malignant tumor across the globe.In recent decades,the medical field has implemented several levels of CRC screening tests,encompassing fecal tests,endoscopic examinations,radiological examinations and blood tests.Previous studies have shown that leukocyte immunoglobulin-like receptor B2(LILRB2)is involved in inhibiting immune cell function,immune evasion,and promoting tumor progression in acute myeloid leukemia and nonsmall cell lung cancer.However,its interaction with CRC has not been reported yet.Recently,a study published in the World Journal of Gastroenterology revealed that LILRB2 and its ligand,angiopoietin-like protein 2,are markedly overexpressed in CRC.This overexpression is closely linked to tumor progression and is indicative of a poor prognosis.The study highlights the potential of utilizing the concentration of LILRB2 in serum as a promising biomarker for tumors.However,there is still room for discussion regarding the data processing and analysis in this research.
基金supported by the National Natural Science Foundation of China,No.81170577
文摘Regenerative capacity is weak after central nervous system injury because of the absence of an enhancing microenvironment and presence of an inhibitory microenvironment for neuronal and axonal repair. In addition to the Nogo receptor（Ng R）, the paired immunoglobulin-like receptor B（Pir B） is a recently discovered coreceptor of Nogo, myelin-associated glycoprotein, and myelin oligodendrocyte glycoprotein. Concurrent blocking of Ng R and Pir B almost completely eliminates the inhibitory effect of myelin-associated inhibitory molecules on axonal regeneration. Pir B participates in a key pathological process of the nervous system, specifically axonal regeneration inhibition. Pir B is an inhibitory receptor similar to Ng R, but their effects are not identical. This study summarizes the structure, distribution, relationship with common nervous system diseases, and known mechanisms of Pir B, and concludes that Pir B is also distributed in cells of the immune and hematopoietic systems. Further investigations are needed to determine if immunomodulation and blood cell migration involve inhibition of axonal regeneration.
基金supported by the National Natural Science Foundation of China,No.81171178the Natural Science Foundation of Shanxi Province in China,No.2012011036-3the Research Project of Shanxi Scholarship Council of China,No.2012-047
文摘Paired immunoglobulin-like receptor B（Pir B） is a functional receptor of myelin-associated inhibitors for axonal regeneration and synaptic plasticity in the central nervous system, and thus suppresses nerve regeneration. The regulatory effect of Pir B on injured nerves has received a lot of attention. To better understand nerve regeneration inability after spinal cord injury, this study aimed to investigate the distribution of Pir B（via immunofluorescence） in the central nervous system and peripheral nervous system 10 days after injury. Immunoreactivity for Pir B increased in the dorsal root ganglia, sciatic nerves, and spinal cord segments. In the dorsal root ganglia and sciatic nerves, Pir B was mainly distributed along neuronal and axonal membranes. Pir B was found to exhibit a diffuse, intricate distribution in the dorsal and ventral regions. Immunoreactivity for Pir B was enhanced in some cortical neurons located in the bilateral precentral gyri. Overall, the findings suggest a pattern of Pir B immunoreactivity in the nervous system after unilateral spinal transection injury, and also indicate that Pir B may suppress repair after injury.
基金the Swedish Institute, No. 00287/2006210the North Sweden Cancer Foundation, Specialized Research Fund for the Doctoral Program New Teacher of Higher Education by the Chinese Ministry of Education, No. 200804861039the National Natural Science Foundation of China, No. 30973073, 30973072
文摘The current study investigated correlations between the expression of leucine-rich repeats and immunoglobulin-like domain 1 （LRIG1） and antioxidant enzymes and related proteins, including manganese superoxide dismutase, glutamate cysteine ligase catalytic or regulatory subunit, thioredoxin and thioredoxin reductase, in both human ependymoma and oligodendroglioma. Results revealed that the cytoplasmic expression of LRIG1 was associated with expression of glutamate cysteine ligase catalytic subunit in the human ependymoma, while the nuclear expression of LRIG1 was associated with expression of thioredoxin reductase. In human oligodendroglioma, the cytoplasmic expression of LRIG1 was associated with expression of the glutamate cysteine ligase catalytic subunit. Both the nuclear and perinuclear expressions of LRIG1 were associated with expression of glutamate cysteine ligase regulatory subunit. These results indicated that several antioxidant enzymes and related proteins contributed to LRIG1 expression, and that these may participate in the antioxidation of the cells.
基金supported by the Start-up Fund for new faculty from the Hong Kong Polytechnic University(PolyU)(A0043215)(to SA)the General Research Fund and Research Impact Fund from the Hong Kong Research Grants Council(15106018,R5032-18)(to DYT)+1 种基金the Research Center for SHARP Vision in PolyU(P0045843)(to SA)the InnoHK scheme from the Hong Kong Special Administrative Region Government(to DYT).
文摘Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.
基金supported by the National Natural Science Foundation of China(Grant Nos.32120103010,32002050)Beijing Joint Research Program for Germplasm Innovation and New Variety Breeding(Grant No.G20220628003-03)the Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences。
文摘Tomato is an important economic crop all over the world.Volatile flavors in tomato fruit are key factors influencing consumer liking and commercial quality.However,the regulatory mechanism controlling the volatile flavors of tomatoes is still not clear.Here,we integrated the metabolome and transcriptome of the volatile flavors in tomato fruit to explore the regulatory mechanism of volatile flavor formation,using wild and cultivated tomatoes with significant differences in flavors.A total of 35 volatile flavor compounds were identified,based on the solid phase microextraction-gas chromatography-mass spectrometry(SPME-GC-MS).The content of the volatiles,affecting fruit flavor,significantly increased in the transition from breaker to red ripe fruit stage.Moreover,the total content of the volatiles in wild tomatoes was much higher than that in the cultivated tomatoes.The content variations of all volatile flavors were clustered into 10 groups by hierarchical cluster and Pearson coefficient correlation(PCC)analysis.The fruit transcriptome was also patterned into 10 groups,with significant variations both from the mature green to breaker fruit stage and from the breaker to red ripe fruit stage.Combining the metabolome and the transcriptome of the same developmental stage of fruits by co-expression analysis,we found that the expression level of 1182 genes was highly correlated with the content of volatile flavor compounds,thereby constructing two regulatory pathways of important volatile flavors.One pathway is tetrahydrothiazolidine N-hydroxylase(SlTNH1)-dependent,which is regulated by two transcription factors(TFs)from the bHLH and AP2/ERF families,controlling the synthesis of 2-isobutylthiazole in amino acid metabolism.The other is lipoxygenase(Sl LOX)-dependent,which is regulated by one TF from the HD-Zip family,controlling the synthesis of hexanal and(Z)-2-heptenal in fatty acid metabolism.Dual-luciferase assay confirmed the binding of b HLH and AP2/ERF to their structural genes.The findings of this study provide new insights into volatile flavor formation in tomato fruit,which can be useful for tomato flavor improvement.
基金funded by State Key Laboratory of North China Crop Improvement and Regulation(NCCIR2023ZZ-10)the National Natural Science Foundation of China(32172384 and 31501623)+1 种基金the Natural Science Foundation of Hebei(C2020204028)the Science and Technology Research Project of Higher Education of Hebei(ZC2023178).
文摘The NAC(NAM,ATAF1/2,and CUC2)is a defense-associated transcription factor(TF)family that positively regulates defense responses to pathogen infection.TaNAC069 positively regulates resistance in wheat to Puccinia triticina(Pt).However,the molecular mechanism of its interaction with a Pt effector is not clear.We found that Pt effector Pt-1234 interacts with TaNAC069 to subvert host immunity during Pt infection.Quantitative real-time PCR analysis showed that expression of Pt-1234 was significantly upregulated during the early stage of Pt infection.Protein-mediated cell death assays in wheat showed that the Pt-1234 protein was unable to induce cell death in wheat near-isogenic lines carrying different leaf rust resistance genes,whereas it suppressed BAX-induced cell death in leaves of Nicotiana benthamiana.Silencing of Pt-1234 by host-induced gene silencing(HIGS)significantly reduced the virulence of Pt in the susceptible wheat variety Thatcher.The C subdomain of TaNAC069 was responsible for its interaction with Pt-1234,and the E subdomain was required for TaNAC069-mediated defense responses to Pt in planta.These findings indicate that Pt utilizes Pt-1234 to interact with wheat transcription factor TaNAC069 through its C subdomain,thereby modulating wheat immunity.
基金supported by grants from the National Natural Science Foundation of China(Grant No.32072571)the 111 Project(Grant No.B17043)the Construction of Beijing Science,and Technology Innovation and Service Capacity in Top Subjects(Grant No.CEFF-PXM2019_014207_000032)。
文摘Tomato(Solanum lycopersicum)is an important fruit and vegetable crop in worldwide.The fertility of tomato reproductive organs can be dramatically decreased when ambient temperatures rise above 35°C,reducing tomato fruit yield.It is necessary to identify transcription factors(TFs)and target genes involved in heat stress response(HSR)signaling cascades in tomato flower buds to improve tomato plant thermotolerance.In this study,we profiled genes expressed in three developmental stages of tomato flower buds.Red and turquoise modules for heat stress(HS)were identified through gene co-expression network analysis,and the genes within these modules were enriched in HS-related pathways.By focusing on the TFs in the two modules,we identified several novel HSR-related TFs,including SlWRKY75,SlMYB117,and SlNAM.Furthermore,homology analysis illustrated a conserved signaling cascade in tomato.Lastly,we identified and experimentally validated four HSF-regulated genes,namely SlGrpE,SlERDJ3A,SlTIL,and SlPOM1,that likely modulate thermotolerance in plants.These results provide a high-resolution atlas of gene expression during tomato flower bud development under HS conditions,which is a valuable resource for uncovering potential regulatory networks associated with the HSR in tomato.
基金supported by Research Program for Agricultural Science and Technology Development,Republic of Korea(PJ01570601)the Fellowship Program(PJ01661001)of the National Institute of Agricultural Sciences,Republic of KoreaRural Development Administration,Republic of Korea.
文摘The emergence of novel phytopathogens and the accelerated spread of plant diseases to new regions,driven by global climate change,constitute significant threats to agricultural resources.Rice,a major tropical staple crucial for global food security,possesses six transcription factor superfamilies-AP2/ERF,bHLH,bZIP,MYB,NAC,and WRKY-that function in innate immunity against pathogens.We review their biological functions and regulatory mechanisms in rice immunity.
基金supported by the National Natural Science Foundation of China(Nos.82171552 and 82170479)the Natural Science Foundation of Shanghai Ctiy(No.21ZR1457500)the Science and Technology Bureau of Shanghai Putuo District(No.ptkwws202102).
文摘Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.
文摘BACKGROUND Diabetic retinopathy(DR)is a major microvascular complication of diabetes mellitus,leading to significant visual impairment and blindness among adults.Current treatment options are limited,making it essential to explore novel therapeutic strategies.Curcumol,a sesquiterpenoid derived from traditional Chinese medicine,has shown anti-inflammatory and anti-cancer properties,but its potential role in DR remains unclear.AIM To investigate the therapeutic effects of curcumol on the progression of DR and to elucidate the underlying molecular mechanisms,particularly its impact on the fat mass and obesity-associated(FTO)protein and the long non-coding RNA(lncRNA)MAF transcription factor G antisense RNA 1(MAFG-AS1).METHODS A streptozotocin-induced mouse model of DR was established,followed by treatment with curcumol.Retinal damage and inflammation were evaluated through histological analysis and molecular assays.Human retinal vascular endothelial cells were exposed to high glucose conditions to simulate diabetic environments in vitro.Cell proliferation,migration,and inflammation markers were assessed in curcumoltreated cells.LncRNA microarray analysis identified key molecules regulated by curcumol,and further experiments were conducted to confirm the involvement of FTO and MAFG-AS1 in the progression of DR.RESULTS Curcumol treatment significantly reduced blood glucose levels and alleviated retinal damage in streptozotocininduced DR mouse models.In high-glucose-treated human retinal vascular endothelial cells,curcumol inhibited cell proliferation,migration,and inflammatory responses.LncRNA microarray analysis identified MAFG-AS1 as the most upregulated lncRNA following curcumol treatment.Mechanistically,FTO demethylated MAFG-AS1,stabilizing its expression.Rescue experiments demonstrated that the protective effects of curcumol against DR were mediated through the FTO/MAFG-AS1 signaling pathway.CONCLUSION Curcumol ameliorates the progression of DR by modulating the FTO/MAFG-AS1 axis,providing a novel therapeutic pathway for the treatment of DR.These findings suggest that curcumol-based therapies could offer a promising alternative for managing this debilitating complication of diabetes.
基金supported by the Natural Science Foundation of Hunan Province,China(2022JJ30886).
文摘Objective:Polycystic ovary syndrome(PCOS)is a common endocrine disorder that affects women’s health.This study aims to investigate gene and transcription factor(TF)expression differences between PCOS patients and healthy individuals using bioinformatics approaches,and to verify the function of key transcription factors,with the goal of providing new insights into the pathogenesis of PCOS.Methods:Differentially expressed genes(DEGs)and differentially expressed transcription factors(DETFs)between PCOS patients and controls were identified from the RNA sequencing dataset GSE168404 using bioinformatics methods.Functional enrichment analysis was performed using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.The expression and function of core transcription factors were further validated in ovarian tissues of PCOS model mice and control mice using Western blotting and reverse transcription quantitative polymerase chain reaction(RTqPCR).Results:A total of 332 DEGs were identified between PCOS patients and controls,including 259 upregulated and 73 downregulated genes in the PCOS group.19 DETFs were further screened,of which 16 were upregulated and 3 were downregulated in PCOS.The upregulated DETFs(including TFCP2L1,DACH1,ESR2,AFF3,SMAD9,ZNF331,HOPX,ATOH8,HIF3α,DPF3,HOXC4,HES1,ID1,JDP2,SOX4,and ID3)were primarily associated with lipid metabolism,development,and cell adhesion.Protein and mRNA expression analysis in PCOS model mice revealed significantly decreased levels of hypoxia-inducible factor(HIF)1αand HIF2α,and significantly increased expression of HIF3αcompared to control mice(all P<0.001).Conclusion:Significant differences in gene and TF expression exist between PCOS patients and healthy individuals.HIF-3αmay play a crucial role in PCOS and could serve as a novel biomarker for diagnosis and a potential therapeutic target.
文摘Loss-of-function variants of low-density lipoprotein receptor-related protein 5(LRP5)can lead to reduced bone formation,culminating in diminished bone mass.Our previous study reported transcription factor osterix(SP7)-binding sites on the LRP5 promoter and its pivotal role in upregulating LRP5 expression during implant osseointegration.However,the potential role of SP7 in ameliorating LRP5-dependent osteoporosis remained unknown.In this study,we used mice with a conditional knockout(c KO)of LRP5 in mature osteoblasts,which presented decreased osteogenesis.The in vitro experimental results showed that SP7 could promote LRP5 expression,thereby upregulating the osteogenic markers such as alkaline phosphatase(ALP),Runt-related transcription factor 2(Runx2),andβ-catenin(P<0.05).For the in vivo experiment,the SP7 overexpression virus was injected into a bone defect model of LRP5 c KO mice,resulting in increased bone mineral density(BMD)(P<0.001)and volumetric density(bone volume(BV)/total volume(TV))(P<0.001),and decreased trabecular separation(Tb.Sp)(P<0.05).These data suggested that SP7 could ameliorate bone defect healing in LRP5 c KO mice.Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.
基金supported by the Natural Science Foundation of Jiangsu Province,China(BK20242007)the Natural Science Foundation of China(32271916)the Jiangsu Agricultural Science and Technology Innovation Fund[CX(24)3048].
文摘bHLH transcription factors,widely exist in various plants,and are vital for the growth and development of these plants.Among them,many have been implicated in anthocyanin biosynthesis across various plants.In the present study,a PdbHLH57 gene,belonging to the bHLH IIIf group,was characterized,which was isolated and cloned from the colored-leaf poplar‘Zhongshancaiyun’(ZSCY).The cDNA sequence of PdbHLH57 was 1887 base pairs,and the protein encoded by PdbHLH57 had 628 amino acids,the isoelectric point and molecular weight of which were 6.26 and 69.75 kDa,respectively.Through bioinformatics analysis,PdbHLH57 has been classified into the IIIf bHLH subgroup,with many members of this subgroup known to participate in anthocyanin biosynthesis.The subcellular localization analysis conducted in the leaf protoplasts of‘ZSCY’revealed that the PdbHLH57 protein is specifically localized in the nucleus.The transcription activation analysis was also conducted,and the results showed that the PdbHLH57 protein had self-transcription activation.To better explore the functions of the PdbHLH57 protein,two parts of this protein(PdbHLH57-1,PdbHLH57-2)were split to detect their transcriptional activation activity.The results indicated that PdbHLH57-1(1-433aa)had self-transcription activation,and PdbHLH57-2(433-628aa)had no transcription activation.The expression of PdbHLH57 peaked in June during different developmental stages in‘ZSCY’,and it was most highly expressed in the phloem among various tissues.These findings offer a basis for understanding the role of PdbHLH57 in colored-leaf poplar.
基金funded by the Fundamental Research Grant Scheme(Grant No.FRGS/1/2023/STG03/UM/02/2)Universiti Malaya RU Grant(RU002-2025B).
文摘Myeloblastosis(MYB)transcription factors(TFs)are evolutionarily conserved regulatory proteins that are crucial for plantgrowth,development,secondarymetabolism,andstress adaptation.Recent studieshavehighlighted their crucial role in coordinating growth–defense trade-offs through transcriptional regulation of key biosynthetic and stress-response genes.Despite extensive functional characterization in model plants such as Arabidopsis thaliana,systematically evaluating the broader functional landscape of MYB TFs across diverse species and contexts remains necessary.This systematic review integrates results from 24 peer-reviewed studies sourced from Scopus and Web of Science,focusing on the functional diversity of MYB TFs,particularly in relation to abiotic stress tolerance,metabolic regulation,and plant developmental processes.Advances in genomic technologies,such as transcriptomics,genome editing,and comparative phylogenetics,have considerably enhanced our understanding of MYB-mediated regulatory mechanisms.These tools have facilitated the identification and functional characterization of MYB genes across model and non-model plant species.Key findings underscore the multifaceted roles of MYB TFs in enhancing stress resilience,modulating anthocyanin and flavonoid biosynthesis,and contributing to yield-related traits,thereby highlighting their potential applications in crop improvement and sustainable agriculture.However,critical gaps exist in understanding MYB interactions within complex regulatory networks,particularly in underrepresented plant species and ecological contexts.This review consolidates current knowledge as well as identifies research gaps and proposes future directions to advance the understanding and application of MYB TFs.The insights derived from this study underscore their transformative potential in addressing global challenges including food security and climate resilience through innovative agricultural practices.
