The Ras/MAPK signaling cascade plays an essential role in the regulation of cellular processes,including proliferation,differentiation,and survival,serving as a pivotal intracellular communication network.Dysregulatio...The Ras/MAPK signaling cascade plays an essential role in the regulation of cellular processes,including proliferation,differentiation,and survival,serving as a pivotal intracellular communication network.Dysregulation of this pathway,frequently attributable to mutations within Ras genes,has been strongly associated with the development of a spectrum of cancers.This review underscores the pivotal role of the Ras/MAPK pathway in oncogenic transformation and tumor progression,briefing the intricate mechanisms through which the aberrant activation of this pathway leads to unbridled cell proliferation,inhibition of apoptosis,promotion of metastasis,and induction of angiogenesis,thereby providing valuable insights into the pathogenesis of malignancies.It also underscores the significance of the Ras/MAPK pathway as a therapeutic target and discusses the challenges and potential of targeted therapies,including combination treatments and personalized medicine approaches,to overcome resistance and enhance treatment efficacy in cancers driven by pathway dysregulation.展开更多
AIM To evaluate the relationship between expression of ras, p53, bcl 2 gene products, and hepatocarcinogenesis since endotoxemia produced from lipopolysaccharide admi nistration and/or the hypophagocytic state of ...AIM To evaluate the relationship between expression of ras, p53, bcl 2 gene products, and hepatocarcinogenesis since endotoxemia produced from lipopolysaccharide admi nistration and/or the hypophagocytic state of splenectomy significantly accelerated hepatocarcinogenesis induced by thioacetamide. 〖WTH4〗METHODS〓〖WTXFZ〗The hepatocarcinoma model was induced by oral intake of 0 03% thioacetamide for six months. During the induction of hepatocarcinoma model, rats were additionally treated with splenectomy and/or lipopolysaccharide administration. The techniques of flow cytometry, immunohistochemistry and immunoelectronmicroscopy were applied to quantitative analysis of the expression of oncogene proteins. RESULTS In this model system, overexpression of ras p21 protein mainly occurred on precancerous cell population or in early stage of hepatocyte transformation. And the levels of ras p21 declined when nuclear DNA aneuploid increased. Expression of bcl 2 protein slowly and steadily rose with more hepatocytes staying in S+G2M phases as the hepatocarcinoma became more malignant. P53 was moderately expressed during the hepatocarcinogenesis. There was no statistical correlation between endotoxemia levels and the changes of ras, p53 and bcl 2 gene products. CONCLUSION Over expression of oncogene ras p21 was likely to be a precursor of the premalignant hepatocytes and it might be responsible for the initiation of hepatocarcinogenesis. Bcl 2 protein expression is proportional to the severity of the malignancies. P53 may be a key pathway on the transformation and development of hepatocarcinoma. This study confirmed the hypothesis that there are multiple genes and multiple steps involved in hepatocarcinogenesis. Expressions of oncogene proteins reflected the properties of the premalignant and malignant cells, but not directly related to endotoxemia statistically.[JP]展开更多
AIM:To explore the effect of miR-184 and miR-205 on the proliferation and metastasis of conjunctival mucosa associated lymphoid tissue(MALT)lymphoma.METHODS:Tissue of tumor and adjacent normal control from 5 patients ...AIM:To explore the effect of miR-184 and miR-205 on the proliferation and metastasis of conjunctival mucosa associated lymphoid tissue(MALT)lymphoma.METHODS:Tissue of tumor and adjacent normal control from 5 patients with conjunctival MALT was included.RPMI8226 cell line was selected to verify the effect of mi RNAs in B cells.The function of micro RNA on the RPMI8226 cell apoptosis,migration and invasion was evaluated by apoptosis assay and Transwell assay.The m RNA and protein expression were examined by quantitative RT-PCR and Western blotting.The effect of micro RNA on regulation of downstream gene expression was evaluated by luciferase report assay.RESULTS:A decreased level of miR-184 and miR-205 was observed in MALT lymphoma tissue.Exogenous miR-184 and miR-205 analogues promoted apoptosis,and inhibited the survival,migration,and invasion of RPMI8226 cells.miR-184 and miR-205 inhibitor reversed the process.The RNA and protein level of Ras L10 B and TNFAIP8 were downregulated in MALT lymphoma tissue.The exogenous of miR-184 and miR-205 promoted the expression of Ras L10 B and TNFAIP8.Meanwhile,inhibition of miR-184 and miR-205 repressed the expression of target gene,Ras L10 B and TNFAIP8.CONCLUSION:miR-184 and miR-205 suppresses the tumorigenesis of conjunctival MALT lymphoma through regulating Ras L10 B and TNFAIP8.展开更多
Researchers from the Institute of Genetics and Developmental Biology(IGDB)of the Chinese Academy of Sciences,with collaborators,identified two sorghum genes(SbSLT1 and SbSLT2)that block Striga-a parasitic plant,also k...Researchers from the Institute of Genetics and Developmental Biology(IGDB)of the Chinese Academy of Sciences,with collaborators,identified two sorghum genes(SbSLT1 and SbSLT2)that block Striga-a parasitic plant,also known as“witchweed,”that causes$1.5 billion annual losses in Africa by draining crop nutrients.Published in Cell(February 12,2025),the study shows that these genes regulate strigolactones(SLs).展开更多
The point mutation at codons 12 and 61 of c-Ha-ras gene,at codon 12 of N-ras gene and at codons 12 and 13 of K-ras gene was observed in formalin-fixed and paraffin-embedded tissue specimens of 42 cases of gastric canc...The point mutation at codons 12 and 61 of c-Ha-ras gene,at codon 12 of N-ras gene and at codons 12 and 13 of K-ras gene was observed in formalin-fixed and paraffin-embedded tissue specimens of 42 cases of gastric cancer with PCR-RFLP method. It was found that the point mutation at codon 12 of c-Ha-ras occurred in 14 cases out of the 42(33. 3%) and that at codon 12 of K-ras in 2 cases(4. 8%). Statistical analysis showed that the point mutation of ras genes plays an itnportant role in the prognosis for the patients with gastric cancer.展开更多
By in situ hybridization and immunohistochemistry, the expression of c H ras, c fos, c jun and p 53 genes was studied in 11 human cirrhotic liver fragments and 7 histologically normal livers. The results showed ...By in situ hybridization and immunohistochemistry, the expression of c H ras, c fos, c jun and p 53 genes was studied in 11 human cirrhotic liver fragments and 7 histologically normal livers. The results showed that no abnormal expression was found in normal livers. By contrast, 10 out of 11 cirrhotic speciments(91%) displayed abnormally overexpression of c H ras transcripts; five cirrhotic samples revealed increased level of c fos mRNA; only one case exhibited increased level of c jun mRNA. Mutated p 53 protein was all negative, as assessed by immunohistochemistry, in the cirrhotic livers. These data suggest that the overexpression of ras and fos genes might consititute part of an early event of gene abnormality predisposing to the later development of hepatocellular carcinoma.展开更多
The Ras gene,a conserved member of the insulin pathway,andβ-glucosidase gene,an important cellulase,are two important growth-related genes.However,there is no study on the association between mutations of these two g...The Ras gene,a conserved member of the insulin pathway,andβ-glucosidase gene,an important cellulase,are two important growth-related genes.However,there is no study on the association between mutations of these two genes and growth traits in bivalves.Here,the polymorphism of these two genes in Crassostrea gigas were revealed.Their association with growth traits was evaluated in 290 oysters from five families,and was further confirmed in another 186 oysters from three fast-growing strains.Seventeen and twelve SNPs were identified in the Ras gene andβ-glucosidase gene,respectively.Among these SNPs,four SNPs in each gene(Ras:C.86C>A,C.90T>C,C.112A>G and C.118G>A;β-glucosidase:C.247G>A,C.284C>T,C.1260C>T and C.1293T>C)were significantly(P<0.05)associated with the growth of these oysters.Furthermore,eight and nine haplotypes were constructed in the Ras gene andβ-glucosidase gene,respectively.Oysters with both haplotypes R-Hap5(CCAA)andβ-Hap7(ACCT),or with both R-Hap 6(ATGG)andβ-Hap 6(ACTC),or with both R-Hap 6 andβ-Hap 9(ACTT),or with both R-Hap 7(ATAA)andβ-Hap 7,showed the highest growth performances.These results provide candidate markers for selecting C.gigas with fast growth.展开更多
Objective: To investigate the effects of DNA methylation and histone deacetylase inhibitors in the re-expression of P16 and RASSIF1A of QBC939. Methods: The QBC939 cells were treated with hydralazine and valproate eit...Objective: To investigate the effects of DNA methylation and histone deacetylase inhibitors in the re-expression of P16 and RASSIF1A of QBC939. Methods: The QBC939 cells were treated with hydralazine and valproate either alone or combined, and the control group was added with RPIM-1640 culture medium. After 48 h, the expression of P16 and RASSF1A genes were evaluated by reverse transcription-PCR, Western blot, and the methylation status of the two genes were detected with MSP (methylation specific PCR). Results: Hydralazine and valproate could induce demethylation of the promoter region of the two genes, and could make them re-active. The expressions of P16 and RASSF1A of cells treated with both drugs were higher than that of the cells treated with either hydralazine or valproate (P < 0.01). There was no RASSF1A gene, and few P16 gene expressing in the control group. The demethylation effect could be found in the groups treated with hydralazine or both drugs, whereas no demethylation effect happened in the valproate group. Conclusion: The two drugs could synergistically re-express P16 and RASSF1A genes silenced in QBC939, and they exerted a great anti-tumour effect on QBC cells.展开更多
Objective: To observe the series of pathological changes during the development of gastric adenocarcinoma in ulcerative rats induced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), and the expression profile of relat...Objective: To observe the series of pathological changes during the development of gastric adenocarcinoma in ulcerative rats induced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), and the expression profile of related oncogenic protein.Methods: MNNG was administered in rats with ulcers due to acetic acid treatment to induce gastric cancer, and the protein expressions of ras and c-erbB2 genes in the ulcer were examined immunohistochemically along with pathological examination.Results: The incidence of gastric adenocarcinoma in the model group reaches 40% (6/15), while none of the rats developed cancer in the control group with ulcers.Positive expressions of the proteins of p21ras and c-erbB2 were observed in the tissues undergoing canceration in the 6 rats of model group, but were not observed in the 5 control rats; p53 protein expression, however, failed to be detected in both groups.Conclusion: A new animal model of gastric cancer has been established in rats with gastric ulcer after MNNG treatment, which may facilitate the pharmacological research of gastric cancer.展开更多
Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in...Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in enduring neurological deficits.Recent findings from our research indicate that inhibition of Rho-associated kinase(ROCK)2 facilitates neuroprotection in different models of central nervous system diseases.In addition,our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons.However,it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis.In this study,we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus(AAV)vector(AAV-sh.ROCK2).We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo.Furthermore,AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury.Notably,AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury.Mechanistically,AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression.Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis,highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.展开更多
A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an or...A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.展开更多
Antibiotic resistance genes(ARGs) are recognized as a primary threat to the sustainability of environment and human health in the 21^(st) century.Nanomaterials(NMs) have attracted substantial attention due to their un...Antibiotic resistance genes(ARGs) are recognized as a primary threat to the sustainability of environment and human health in the 21^(st) century.Nanomaterials(NMs) have attracted substantial attention due to their unique dimensions and structures.Unfortunately,emerging evidence suggests that NMs may facilitate the transmission of ARGs.It is crucial to elucidate how NMs affect the evolution and dissemination of ARGs.The current review comprehensively examines the role of NMs in the widespread transmission of ARGs in aquatic environments and the underlying mechanisms involved in the process.It aims to clarify the effects and mechanisms of NMs on the horizontal gene transfer processes that are associated with ARGs,including the enhancement of cell membrane permeability,the formation of nanopores on membranes,promotion of mutagenesis,and the generation of reactive oxygen species(ROSs).Furthermore,the trade-off between the removal of ARGs and horizontal transfer has been elucidated.The review aspires to guide future research directions,advance knowledge on the implications of NMs in the field of ARGs' transmission,and provide a theoretical foundation for the development of safer and more effective applications of NMs.展开更多
AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induc...AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induced in Wistar rats through subcutaneous injection of lipopolysaccharide(LPS,200μg)and the rats were then randomly assigned to EIU group(n=5)and the HPS intervention group(n=5).HPS(400 mg/kg,intraperitoneally)or its carrier was administered 24h and 1h prior to EIU induction.Eyes were examined and enucleated 24h post-induction,and total RNA was extracted from the iris-ciliary body.Gene expression microarrays were used to identify differentially expressed genes(DEGs),followed by bioinformatics analyses,including gene ontology(GO)and pathway analysis.Key findings were not experimentally validated at the mRNA or protein level.RESULTS:A total of 322 DEGs were identified,comprising 254 mRNA and 68 lncRNA genes.GO analysis revealed significant functional categories,including response to LPS.Pathway analysis identified key signaling pathways involved in uveitis,such as cytokine-cytokine receptor interactions.Notably,16 mRNA and 7 lncRNA DEGs emerged as central nodes in the gene correlation network.CONCLUSION:HPS exerts its anti-inflammatory effects through coordinated signaling pathways,offering insights into potential therapeutic targets for managing uveitis.展开更多
Aspergillus species are ubiquitous fungi that produce mycotoxins(secondary metabolites)known as sterigmatocystin and aflatoxins in many different kinds of foods,which leads to serious contamination in agricultural pro...Aspergillus species are ubiquitous fungi that produce mycotoxins(secondary metabolites)known as sterigmatocystin and aflatoxins in many different kinds of foods,which leads to serious contamination in agricultural products,thereby endangering human health.Extensive studies on Aspergillus fungi have been conducted on growth and development,aflatoxin biosynthesis,and their interactions with environment.Here,we summarized a series of functional genes of the main Aspergillus fungi relative to toxins occurrence in foods,which revealed the signal transduction mechanisms of their involvement in growth and development,toxin production,and response to light,anticipating providing theoretical guidance on developing control and prevention technologies for mycotoxin contamination in agricultural products to ensure food safety.展开更多
Catalpa bungei,a fast-growing timber tree,is threatened by the lepidopteran pest Omphisa plagialis.Previous studies in our laboratory successfully generated transgenic C.bungei lines overexpressing Cry genes(Cry1Ab,Cr...Catalpa bungei,a fast-growing timber tree,is threatened by the lepidopteran pest Omphisa plagialis.Previous studies in our laboratory successfully generated transgenic C.bungei lines overexpressing Cry genes(Cry1Ab,Cry2A,and Cry9-2)that exhibited resistance to O.plagialis,but their potential impact on soil bacterial communities remains unclear.In this study,we analyzed nine transgenic C.bungei lines(three independent lines for each Cry gene)to characterize their rhizosphere bacterial communities using high-throughput sequencing of the 16S ribosomal DNA(rDNA)V4-V5 regions.A total of 628 amplicon sequence variants(ASVs)were shared among all transgenic and wild-type(WT)lines,forming a stable core microbiome dominated by Proteobacteria,Bacteroidota,Acidobacteriota,and Actinobacteriota.Alpha diversity showed no significant differences,while beta diversity revealed minor but distinct compositional shifts.Cry1Ab lines exhibited higher abundances of fast-growing taxa,particularly Proteobacteria and Bacteroidota;Cry2A lines displayed intermediate profiles,whereas Cry9-2 lines were nearly indistinguishable from WT communities.Linear discriminant analysis of the effect size revealed significant enrichment of taxa such as Burkholderiaceae and Ralstonia in the Cry1Ab rhizosphere,in contrast to the higher abundance of Chloroflexi in the WT.Functional predictions indicated consistent metabolic pathways across all treatments,suggesting strong ecological redundancy.This study demonstrates minimal impact on rhizosphere microbial communities in transgenic C.bungei plants.The Cry9-2 construct exhibited superior environmental stability,whereas the Cry1Ab construct caused only slight but ecologically acceptable shifts.These findings support the ecological safety of Bt-transgenic C.bungei and identify Cry9-2 as a particularly favorable candidate for forestry applications.This comparative evaluation of three Cry genes in a tree species provides a framework for future gene-specific biosafety assessments in woody plants.展开更多
Background:Alzheimer's disease(AD)represents the most prevalent neurodegenerative disorder,with mitochondrial dysfunction being observed in both AD patients and mouse models.Nonetheless,further investigation is re...Background:Alzheimer's disease(AD)represents the most prevalent neurodegenerative disorder,with mitochondrial dysfunction being observed in both AD patients and mouse models.Nonetheless,further investigation is required to elucidate the pathogenic genes associated with AD and to develop early diagnostic methodologies centered on mitochondrial function.Methods:In this study,the dataset GSE132903 was retrieved from the GEO database,encompassing both non-demented(ND)control and AD samples.Through the combination of differential expression gene analysis,weighted gene co-expression network analysis,and intersection with mitochondrial database gene sets,four hub genes associated with AD were identified.These four hub genes were subsequently validated in APP/PS1 and 5xFAD mouse models using molecular biology techniques.Results:The hub genes identified through bioinformatics analysis include SYNJ2BP,VDAC1,NUBPL,and COX19.Within the GSE132903 dataset,the expression levels of SYNJ2BP,NUBPL,and COX19 were significantly elevated in the AD group compared to the non-demented(ND)group,whereas VDAC1 expression was reduced in the AD group relative to the ND group.Furthermore,in the hippocampus of APP/PS1 and 5xFAD mouse models,the expression patterns of SYNJ2BP and NUBPL were consistent with the bioinformatics analysis results.Conclusion:Hub genes identified here through bioinformatics and molecular biology may help early diagnosis of AD patients and may also help build new AD models to explore its pathogenesis.展开更多
Cell competition is an evolutionarily ancient mechanism that functions to remove unfit or dangerous clonal cells in a multicellular community.A classical model is the removal of polarity-deficient clones,such as the p...Cell competition is an evolutionarily ancient mechanism that functions to remove unfit or dangerous clonal cells in a multicellular community.A classical model is the removal of polarity-deficient clones,such as the precancerous scribble(scrib)mutant clones,in Drosophila imaginal discs.The activation of Ras,Yki,or Notch signaling robustly reverses the scrib mutant clonal fate from elimination to tumorous growth.Whether these signals converge to adopt a common mechanism to overcome the elimination pressure posed by cell competition remains unclear.Using single-cell transcriptomics,we find that a critical converging point downstream of Ras,Yki,and Notch signals is the upregulation of Upd2,an IL-6 family cytokine.Overexpression of Upd2 is sufficient to rescue the scrib mutant clones from elimination.Depletion of Upd2 blocks the growth of the scrib mutant clones with active Ras,Yki,and Notch signals.Moreover,Upd2 overexpression promotes robust intestinal stem cell(ISC)proliferation,while Upd2 is intrinsically required in ISCs for the growth of the adult intestine.Together,these results identify Upd2 as a crucial cell fitness factor that sustains tissue growth but can potentiate tumorigenesis when deregulated.展开更多
As a large family of RNA helicases,DEAD-box(DDX)RNA helicases play crucial roles in almost all cellular RNA processing activities.However,the role of the DDX gene family in cold tolerance of mei(Prunus mume)remains un...As a large family of RNA helicases,DEAD-box(DDX)RNA helicases play crucial roles in almost all cellular RNA processing activities.However,the role of the DDX gene family in cold tolerance of mei(Prunus mume)remains unclear.In this study,we identified 45 DDX genes through whole-genome analysis unevenly distributed across eight chromosomes and scaffolds of mei.Based on the phylogenetic tree and gene structure analysis,the DDX genes were classified into nine subfamilies based on their motif compositions and intron-exon structures.The results of synteny analysis showed that segmental duplication was considered a major factor contributing to the amplification of the PmDDX family.RNA-Seq and qRT-PCR results revealed differential expression of PmDDX genes under cold stress.Among these,PmDDX39 was significantly up-regulated under cold stress,suggesting its positive role in modulating mei cold tolerance.We found that silenced PmDDX39 under cold stress led to greater damage than the wild seedlings via virus-induced gene silencing(VIGS).Conversely,overexpression of PmDDX39 in Arabidopsis enhanced cold stress tolerance.Moreover,dual luciferase and yeast one-hybrid(Y1H)demonstrated that PmDDX39 directly activates the expression of the C-repeat binding factor(PmCBFf)by binding to its promoters.This study provides new insights into the structure,evolution,and functional role of the PmDDX gene family in mei responses to cold stress.展开更多
The transcriptomes of three different parts of the fertile tetrasporophyte of Gracilariopsis lemaneiformis,including tip(T),middle(M),and subjacent(S)parts,with a gradual tetrasporangium maturity were analyzed and com...The transcriptomes of three different parts of the fertile tetrasporophyte of Gracilariopsis lemaneiformis,including tip(T),middle(M),and subjacent(S)parts,with a gradual tetrasporangium maturity were analyzed and compared to identify the genes involved in the process of tetrasporogenesis.The number of differentially expressed genes(DEGs)for the Gple-S versus Gple-T comparison was 10296,and the numbers of DEGs for the Gple-S versus Gple-M and Gple-T versus Gple-M comparisons were 7435 and 1337,respectively.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed,and the results showed the enrichment of 132 KEGG pathways(corrected P<0.05).A total of 58 DEGs related to meiosis were screened and blasted against 18 meiosis-related genes(dmc1,mlh1,mnd1,msh4,msh2,msh6,mre11,pds5,pms1,rad21,rad50,rad51,smc1,smc2,smc4,smc5,smc6,and spo11),including four meiosis-specific genes.The transcriptome comparison indicated that in the T part,the meiosis,ribosome,and RNA transport-related genes were mostly up-regulated compared with those in the other two groups.In the M part,the genes related to ribosomes and the endoplasmic reticulum were also up-regulated compared with those in the lower part.Finally,in the S part,the genes associated with photosynthesis were mostly up-regulated,which might be helpful to the recovery from spore formation and release.展开更多
基金supported by the Sichuan Outstanding Youth Fund Project(23NSFJQ0099)the Chengdu Science and Technology Bureau(2024-YF05-02599-SN).
文摘The Ras/MAPK signaling cascade plays an essential role in the regulation of cellular processes,including proliferation,differentiation,and survival,serving as a pivotal intracellular communication network.Dysregulation of this pathway,frequently attributable to mutations within Ras genes,has been strongly associated with the development of a spectrum of cancers.This review underscores the pivotal role of the Ras/MAPK pathway in oncogenic transformation and tumor progression,briefing the intricate mechanisms through which the aberrant activation of this pathway leads to unbridled cell proliferation,inhibition of apoptosis,promotion of metastasis,and induction of angiogenesis,thereby providing valuable insights into the pathogenesis of malignancies.It also underscores the significance of the Ras/MAPK pathway as a therapeutic target and discusses the challenges and potential of targeted therapies,including combination treatments and personalized medicine approaches,to overcome resistance and enhance treatment efficacy in cancers driven by pathway dysregulation.
文摘AIM To evaluate the relationship between expression of ras, p53, bcl 2 gene products, and hepatocarcinogenesis since endotoxemia produced from lipopolysaccharide admi nistration and/or the hypophagocytic state of splenectomy significantly accelerated hepatocarcinogenesis induced by thioacetamide. 〖WTH4〗METHODS〓〖WTXFZ〗The hepatocarcinoma model was induced by oral intake of 0 03% thioacetamide for six months. During the induction of hepatocarcinoma model, rats were additionally treated with splenectomy and/or lipopolysaccharide administration. The techniques of flow cytometry, immunohistochemistry and immunoelectronmicroscopy were applied to quantitative analysis of the expression of oncogene proteins. RESULTS In this model system, overexpression of ras p21 protein mainly occurred on precancerous cell population or in early stage of hepatocyte transformation. And the levels of ras p21 declined when nuclear DNA aneuploid increased. Expression of bcl 2 protein slowly and steadily rose with more hepatocytes staying in S+G2M phases as the hepatocarcinoma became more malignant. P53 was moderately expressed during the hepatocarcinogenesis. There was no statistical correlation between endotoxemia levels and the changes of ras, p53 and bcl 2 gene products. CONCLUSION Over expression of oncogene ras p21 was likely to be a precursor of the premalignant hepatocytes and it might be responsible for the initiation of hepatocarcinogenesis. Bcl 2 protein expression is proportional to the severity of the malignancies. P53 may be a key pathway on the transformation and development of hepatocarcinoma. This study confirmed the hypothesis that there are multiple genes and multiple steps involved in hepatocarcinogenesis. Expressions of oncogene proteins reflected the properties of the premalignant and malignant cells, but not directly related to endotoxemia statistically.[JP]
文摘AIM:To explore the effect of miR-184 and miR-205 on the proliferation and metastasis of conjunctival mucosa associated lymphoid tissue(MALT)lymphoma.METHODS:Tissue of tumor and adjacent normal control from 5 patients with conjunctival MALT was included.RPMI8226 cell line was selected to verify the effect of mi RNAs in B cells.The function of micro RNA on the RPMI8226 cell apoptosis,migration and invasion was evaluated by apoptosis assay and Transwell assay.The m RNA and protein expression were examined by quantitative RT-PCR and Western blotting.The effect of micro RNA on regulation of downstream gene expression was evaluated by luciferase report assay.RESULTS:A decreased level of miR-184 and miR-205 was observed in MALT lymphoma tissue.Exogenous miR-184 and miR-205 analogues promoted apoptosis,and inhibited the survival,migration,and invasion of RPMI8226 cells.miR-184 and miR-205 inhibitor reversed the process.The RNA and protein level of Ras L10 B and TNFAIP8 were downregulated in MALT lymphoma tissue.The exogenous of miR-184 and miR-205 promoted the expression of Ras L10 B and TNFAIP8.Meanwhile,inhibition of miR-184 and miR-205 repressed the expression of target gene,Ras L10 B and TNFAIP8.CONCLUSION:miR-184 and miR-205 suppresses the tumorigenesis of conjunctival MALT lymphoma through regulating Ras L10 B and TNFAIP8.
文摘Researchers from the Institute of Genetics and Developmental Biology(IGDB)of the Chinese Academy of Sciences,with collaborators,identified two sorghum genes(SbSLT1 and SbSLT2)that block Striga-a parasitic plant,also known as“witchweed,”that causes$1.5 billion annual losses in Africa by draining crop nutrients.Published in Cell(February 12,2025),the study shows that these genes regulate strigolactones(SLs).
文摘The point mutation at codons 12 and 61 of c-Ha-ras gene,at codon 12 of N-ras gene and at codons 12 and 13 of K-ras gene was observed in formalin-fixed and paraffin-embedded tissue specimens of 42 cases of gastric cancer with PCR-RFLP method. It was found that the point mutation at codon 12 of c-Ha-ras occurred in 14 cases out of the 42(33. 3%) and that at codon 12 of K-ras in 2 cases(4. 8%). Statistical analysis showed that the point mutation of ras genes plays an itnportant role in the prognosis for the patients with gastric cancer.
文摘By in situ hybridization and immunohistochemistry, the expression of c H ras, c fos, c jun and p 53 genes was studied in 11 human cirrhotic liver fragments and 7 histologically normal livers. The results showed that no abnormal expression was found in normal livers. By contrast, 10 out of 11 cirrhotic speciments(91%) displayed abnormally overexpression of c H ras transcripts; five cirrhotic samples revealed increased level of c fos mRNA; only one case exhibited increased level of c jun mRNA. Mutated p 53 protein was all negative, as assessed by immunohistochemistry, in the cirrhotic livers. These data suggest that the overexpression of ras and fos genes might consititute part of an early event of gene abnormality predisposing to the later development of hepatocellular carcinoma.
基金the National Natural Sci-ence Foundation of China(No.31972789)the Industrial Development Project of Qingdao City(No.20-3-4-16-nsh)the Science and Technology Development Pro-ject of Weihai City(No.2018NS01).
文摘The Ras gene,a conserved member of the insulin pathway,andβ-glucosidase gene,an important cellulase,are two important growth-related genes.However,there is no study on the association between mutations of these two genes and growth traits in bivalves.Here,the polymorphism of these two genes in Crassostrea gigas were revealed.Their association with growth traits was evaluated in 290 oysters from five families,and was further confirmed in another 186 oysters from three fast-growing strains.Seventeen and twelve SNPs were identified in the Ras gene andβ-glucosidase gene,respectively.Among these SNPs,four SNPs in each gene(Ras:C.86C>A,C.90T>C,C.112A>G and C.118G>A;β-glucosidase:C.247G>A,C.284C>T,C.1260C>T and C.1293T>C)were significantly(P<0.05)associated with the growth of these oysters.Furthermore,eight and nine haplotypes were constructed in the Ras gene andβ-glucosidase gene,respectively.Oysters with both haplotypes R-Hap5(CCAA)andβ-Hap7(ACCT),or with both R-Hap 6(ATGG)andβ-Hap 6(ACTC),or with both R-Hap 6 andβ-Hap 9(ACTT),or with both R-Hap 7(ATAA)andβ-Hap 7,showed the highest growth performances.These results provide candidate markers for selecting C.gigas with fast growth.
文摘Objective: To investigate the effects of DNA methylation and histone deacetylase inhibitors in the re-expression of P16 and RASSIF1A of QBC939. Methods: The QBC939 cells were treated with hydralazine and valproate either alone or combined, and the control group was added with RPIM-1640 culture medium. After 48 h, the expression of P16 and RASSF1A genes were evaluated by reverse transcription-PCR, Western blot, and the methylation status of the two genes were detected with MSP (methylation specific PCR). Results: Hydralazine and valproate could induce demethylation of the promoter region of the two genes, and could make them re-active. The expressions of P16 and RASSF1A of cells treated with both drugs were higher than that of the cells treated with either hydralazine or valproate (P < 0.01). There was no RASSF1A gene, and few P16 gene expressing in the control group. The demethylation effect could be found in the groups treated with hydralazine or both drugs, whereas no demethylation effect happened in the valproate group. Conclusion: The two drugs could synergistically re-express P16 and RASSF1A genes silenced in QBC939, and they exerted a great anti-tumour effect on QBC cells.
文摘Objective: To observe the series of pathological changes during the development of gastric adenocarcinoma in ulcerative rats induced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), and the expression profile of related oncogenic protein.Methods: MNNG was administered in rats with ulcers due to acetic acid treatment to induce gastric cancer, and the protein expressions of ras and c-erbB2 genes in the ulcer were examined immunohistochemically along with pathological examination.Results: The incidence of gastric adenocarcinoma in the model group reaches 40% (6/15), while none of the rats developed cancer in the control group with ulcers.Positive expressions of the proteins of p21ras and c-erbB2 were observed in the tissues undergoing canceration in the 6 rats of model group, but were not observed in the 5 control rats; p53 protein expression, however, failed to be detected in both groups.Conclusion: A new animal model of gastric cancer has been established in rats with gastric ulcer after MNNG treatment, which may facilitate the pharmacological research of gastric cancer.
基金supported by the National Natural Science Foundation of China,No.82471327the Natural Science Foundation of ShandongProvince,No.ZR2024MH200(both to SL).
文摘Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in enduring neurological deficits.Recent findings from our research indicate that inhibition of Rho-associated kinase(ROCK)2 facilitates neuroprotection in different models of central nervous system diseases.In addition,our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons.However,it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis.In this study,we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus(AAV)vector(AAV-sh.ROCK2).We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo.Furthermore,AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury.Notably,AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury.Mechanistically,AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression.Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis,highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.
文摘A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.
基金supported by the State Key Laboratory of Urban Water Resource and Environment (Harbin Institute of Technology) (No.2022TS13)the key projects of National Natural Science Foundation of China (No.2019YFC0408503)the Key Research Program of Wuhan (No.2022022202015015)。
文摘Antibiotic resistance genes(ARGs) are recognized as a primary threat to the sustainability of environment and human health in the 21^(st) century.Nanomaterials(NMs) have attracted substantial attention due to their unique dimensions and structures.Unfortunately,emerging evidence suggests that NMs may facilitate the transmission of ARGs.It is crucial to elucidate how NMs affect the evolution and dissemination of ARGs.The current review comprehensively examines the role of NMs in the widespread transmission of ARGs in aquatic environments and the underlying mechanisms involved in the process.It aims to clarify the effects and mechanisms of NMs on the horizontal gene transfer processes that are associated with ARGs,including the enhancement of cell membrane permeability,the formation of nanopores on membranes,promotion of mutagenesis,and the generation of reactive oxygen species(ROSs).Furthermore,the trade-off between the removal of ARGs and horizontal transfer has been elucidated.The review aspires to guide future research directions,advance knowledge on the implications of NMs in the field of ARGs' transmission,and provide a theoretical foundation for the development of safer and more effective applications of NMs.
基金Supported by the National Natural Science Fundation of China(No.82101107No.81471575).
文摘AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induced in Wistar rats through subcutaneous injection of lipopolysaccharide(LPS,200μg)and the rats were then randomly assigned to EIU group(n=5)and the HPS intervention group(n=5).HPS(400 mg/kg,intraperitoneally)or its carrier was administered 24h and 1h prior to EIU induction.Eyes were examined and enucleated 24h post-induction,and total RNA was extracted from the iris-ciliary body.Gene expression microarrays were used to identify differentially expressed genes(DEGs),followed by bioinformatics analyses,including gene ontology(GO)and pathway analysis.Key findings were not experimentally validated at the mRNA or protein level.RESULTS:A total of 322 DEGs were identified,comprising 254 mRNA and 68 lncRNA genes.GO analysis revealed significant functional categories,including response to LPS.Pathway analysis identified key signaling pathways involved in uveitis,such as cytokine-cytokine receptor interactions.Notably,16 mRNA and 7 lncRNA DEGs emerged as central nodes in the gene correlation network.CONCLUSION:HPS exerts its anti-inflammatory effects through coordinated signaling pathways,offering insights into potential therapeutic targets for managing uveitis.
基金supported by the key project of National Natural Sciences Foundation of China(U22A20551,32030085)the Major Project of Hubei Hongshan Laboratory,China(2021hszd015)+2 种基金the Hubei Province Major Science and Technology Special Project,China(2023BBA002)the National Natural Sciences Foundation of China(U22A20551)the National Natural Science Foundation of China Excellent Youth Fund(32422072)。
文摘Aspergillus species are ubiquitous fungi that produce mycotoxins(secondary metabolites)known as sterigmatocystin and aflatoxins in many different kinds of foods,which leads to serious contamination in agricultural products,thereby endangering human health.Extensive studies on Aspergillus fungi have been conducted on growth and development,aflatoxin biosynthesis,and their interactions with environment.Here,we summarized a series of functional genes of the main Aspergillus fungi relative to toxins occurrence in foods,which revealed the signal transduction mechanisms of their involvement in growth and development,toxin production,and response to light,anticipating providing theoretical guidance on developing control and prevention technologies for mycotoxin contamination in agricultural products to ensure food safety.
基金funded by the Chinese Academy of Forestry-Special funds for basic scientific research service expenses of the central level public welfare research institutes(Grant No.CAFYBB2020QD001)the National Natural Science Foundation of China(Grant Nos.32101550,32271917)+1 种基金Jiangsu Agricultural Science and Technology Innovation Fund(Grant No.CX(24)3052)National Forestry and Grassland Administration’s Center for Science and Technology Development Projects(Grant No.KJZXSA202202).
文摘Catalpa bungei,a fast-growing timber tree,is threatened by the lepidopteran pest Omphisa plagialis.Previous studies in our laboratory successfully generated transgenic C.bungei lines overexpressing Cry genes(Cry1Ab,Cry2A,and Cry9-2)that exhibited resistance to O.plagialis,but their potential impact on soil bacterial communities remains unclear.In this study,we analyzed nine transgenic C.bungei lines(three independent lines for each Cry gene)to characterize their rhizosphere bacterial communities using high-throughput sequencing of the 16S ribosomal DNA(rDNA)V4-V5 regions.A total of 628 amplicon sequence variants(ASVs)were shared among all transgenic and wild-type(WT)lines,forming a stable core microbiome dominated by Proteobacteria,Bacteroidota,Acidobacteriota,and Actinobacteriota.Alpha diversity showed no significant differences,while beta diversity revealed minor but distinct compositional shifts.Cry1Ab lines exhibited higher abundances of fast-growing taxa,particularly Proteobacteria and Bacteroidota;Cry2A lines displayed intermediate profiles,whereas Cry9-2 lines were nearly indistinguishable from WT communities.Linear discriminant analysis of the effect size revealed significant enrichment of taxa such as Burkholderiaceae and Ralstonia in the Cry1Ab rhizosphere,in contrast to the higher abundance of Chloroflexi in the WT.Functional predictions indicated consistent metabolic pathways across all treatments,suggesting strong ecological redundancy.This study demonstrates minimal impact on rhizosphere microbial communities in transgenic C.bungei plants.The Cry9-2 construct exhibited superior environmental stability,whereas the Cry1Ab construct caused only slight but ecologically acceptable shifts.These findings support the ecological safety of Bt-transgenic C.bungei and identify Cry9-2 as a particularly favorable candidate for forestry applications.This comparative evaluation of three Cry genes in a tree species provides a framework for future gene-specific biosafety assessments in woody plants.
基金Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences,Grant/Award Number:2023-PT180-01 and 2023-PT330-01Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-034National Natural Science Foundation of China,Grant/Award Number:82161138027。
文摘Background:Alzheimer's disease(AD)represents the most prevalent neurodegenerative disorder,with mitochondrial dysfunction being observed in both AD patients and mouse models.Nonetheless,further investigation is required to elucidate the pathogenic genes associated with AD and to develop early diagnostic methodologies centered on mitochondrial function.Methods:In this study,the dataset GSE132903 was retrieved from the GEO database,encompassing both non-demented(ND)control and AD samples.Through the combination of differential expression gene analysis,weighted gene co-expression network analysis,and intersection with mitochondrial database gene sets,four hub genes associated with AD were identified.These four hub genes were subsequently validated in APP/PS1 and 5xFAD mouse models using molecular biology techniques.Results:The hub genes identified through bioinformatics analysis include SYNJ2BP,VDAC1,NUBPL,and COX19.Within the GSE132903 dataset,the expression levels of SYNJ2BP,NUBPL,and COX19 were significantly elevated in the AD group compared to the non-demented(ND)group,whereas VDAC1 expression was reduced in the AD group relative to the ND group.Furthermore,in the hippocampus of APP/PS1 and 5xFAD mouse models,the expression patterns of SYNJ2BP and NUBPL were consistent with the bioinformatics analysis results.Conclusion:Hub genes identified here through bioinformatics and molecular biology may help early diagnosis of AD patients and may also help build new AD models to explore its pathogenesis.
基金supported by grants to Yan Yan from the Research Grants Council of the Hong Kong Special Administrative Region(GRF16103620,GRF16104324,T13-602/21N)from Shenzhen Science and Technology Innovation Commission(JCYJ20200109140201722)+1 种基金to Toyotaka Ishibashi from the National Natural Science Foundation of China(32170548)to Zongzhao Zhai from the National Natural Science Foundation of China(32170509 and 31871469).
文摘Cell competition is an evolutionarily ancient mechanism that functions to remove unfit or dangerous clonal cells in a multicellular community.A classical model is the removal of polarity-deficient clones,such as the precancerous scribble(scrib)mutant clones,in Drosophila imaginal discs.The activation of Ras,Yki,or Notch signaling robustly reverses the scrib mutant clonal fate from elimination to tumorous growth.Whether these signals converge to adopt a common mechanism to overcome the elimination pressure posed by cell competition remains unclear.Using single-cell transcriptomics,we find that a critical converging point downstream of Ras,Yki,and Notch signals is the upregulation of Upd2,an IL-6 family cytokine.Overexpression of Upd2 is sufficient to rescue the scrib mutant clones from elimination.Depletion of Upd2 blocks the growth of the scrib mutant clones with active Ras,Yki,and Notch signals.Moreover,Upd2 overexpression promotes robust intestinal stem cell(ISC)proliferation,while Upd2 is intrinsically required in ISCs for the growth of the adult intestine.Together,these results identify Upd2 as a crucial cell fitness factor that sustains tissue growth but can potentiate tumorigenesis when deregulated.
基金supported by the Fundamental Research Funds for the Central Universities(Grant No.QNTD202503)Forestry and Grassland Science and Technology Innovation Youth Top Talent Project of China(Grant No.2020132608)Beijing High-Precision Discipline Project,Discipline of Ecological Environment of Urban and Rural Human Settlements.
文摘As a large family of RNA helicases,DEAD-box(DDX)RNA helicases play crucial roles in almost all cellular RNA processing activities.However,the role of the DDX gene family in cold tolerance of mei(Prunus mume)remains unclear.In this study,we identified 45 DDX genes through whole-genome analysis unevenly distributed across eight chromosomes and scaffolds of mei.Based on the phylogenetic tree and gene structure analysis,the DDX genes were classified into nine subfamilies based on their motif compositions and intron-exon structures.The results of synteny analysis showed that segmental duplication was considered a major factor contributing to the amplification of the PmDDX family.RNA-Seq and qRT-PCR results revealed differential expression of PmDDX genes under cold stress.Among these,PmDDX39 was significantly up-regulated under cold stress,suggesting its positive role in modulating mei cold tolerance.We found that silenced PmDDX39 under cold stress led to greater damage than the wild seedlings via virus-induced gene silencing(VIGS).Conversely,overexpression of PmDDX39 in Arabidopsis enhanced cold stress tolerance.Moreover,dual luciferase and yeast one-hybrid(Y1H)demonstrated that PmDDX39 directly activates the expression of the C-repeat binding factor(PmCBFf)by binding to its promoters.This study provides new insights into the structure,evolution,and functional role of the PmDDX gene family in mei responses to cold stress.
基金This research was supported by the Key Program of Science and Technology Innovation in Ningbo(No.2019B10009)the National Natural Science Foundation of China(No.41476111).
文摘The transcriptomes of three different parts of the fertile tetrasporophyte of Gracilariopsis lemaneiformis,including tip(T),middle(M),and subjacent(S)parts,with a gradual tetrasporangium maturity were analyzed and compared to identify the genes involved in the process of tetrasporogenesis.The number of differentially expressed genes(DEGs)for the Gple-S versus Gple-T comparison was 10296,and the numbers of DEGs for the Gple-S versus Gple-M and Gple-T versus Gple-M comparisons were 7435 and 1337,respectively.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed,and the results showed the enrichment of 132 KEGG pathways(corrected P<0.05).A total of 58 DEGs related to meiosis were screened and blasted against 18 meiosis-related genes(dmc1,mlh1,mnd1,msh4,msh2,msh6,mre11,pds5,pms1,rad21,rad50,rad51,smc1,smc2,smc4,smc5,smc6,and spo11),including four meiosis-specific genes.The transcriptome comparison indicated that in the T part,the meiosis,ribosome,and RNA transport-related genes were mostly up-regulated compared with those in the other two groups.In the M part,the genes related to ribosomes and the endoplasmic reticulum were also up-regulated compared with those in the lower part.Finally,in the S part,the genes associated with photosynthesis were mostly up-regulated,which might be helpful to the recovery from spore formation and release.
