Cancer stem cells(CSCs)are widely acknowledged as primary mediators to the initiation and progression of tumors.The association between microbial infection and cancer stemness has garnered considerable scholarly inter...Cancer stem cells(CSCs)are widely acknowledged as primary mediators to the initiation and progression of tumors.The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years.Porphyromonas gingivalis(P.gingivalis)is increasingly considered to be closely related to the development of oral squamous cell carcinoma(OSCC).Nevertheless,the role of P.gingivalis in the stemness of OSCC cells remains uncertain.Herein,we showed that P.gingivalis was positively correlated with CSC markers expression in human OSCC specimens,promoted the stemness and tumorigenicity of OSCC cells,and enhanced tumor formation in nude mice.Mechanistically,P.gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1(SCD1)expression,a key enzyme involved in lipid metabolism,which ultimately resulted in enhanced acquisition of stemness.Moreover,SCD1 suppression attenuated P.gingivalis-induced stemness of OSCC cells,including CSCs markers expression,sphere formation ability,chemoresistance,and tumor growth,in OSCC cells both in vitro and in vivo.Additionally,upregulation of SCD1 in P.gingivalis-infected OSCC cells was associated with the expression of KLF5,and that was modulated by P.gingivalis-activated NOD1 signaling.Taken together,these findings highlight the importance of SCD1-dependent lipid synthesis in P.gingivalis-induced stemness acquisition in OSCC cells,suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.展开更多
Background:Benign prostatic hyperplasia(BPH)is the most common disease in elderly men.There is increasing evidence that periodontitis increases the risk of BPH,but the specific mechanism remains unclear.This study aim...Background:Benign prostatic hyperplasia(BPH)is the most common disease in elderly men.There is increasing evidence that periodontitis increases the risk of BPH,but the specific mechanism remains unclear.This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis(P.gingivalis)in the development of BPH.Methods:The subgingival plaque(Sp)and prostatic fluid(Pf)of patients with BPH concurrent periodontitis were extracted and cultured for 16S r DNA sequencing.Ligature-induced periodontitis,testosterone-induced BPH and the composite models in rats were established.The P.gingivalis and its toxic factor P.gingivalis lipopolysaccharide(P.gLPS)were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate.P.g-LPS was used to construct the prostate cell infection model for mechanism exploration.Results:P.gingivalis,Streptococcus oralis,Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Sp and Pf of patients with BPH concurrent periodontitis,and the average relative abundance of P.gingivalis was found to be the highest.P.gingivalis was detected in both Sp and Pf in 62.5%of patients.Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes.P.gingivalis and P.gLPS infection could induce obvious hyperplasia of the prostate epithelium and stroma(epithelial thickness was 2.97-fold and 3.08-fold that of control group,respectively),and increase of collagen fibrosis(3.81-fold and 5.02-fold that of control group,respectively).P.gingivalis infection promoted prostate cell proliferation,inhibited apoptosis,and upregulated the expression of inflammatory cytokines interleukin-6(IL-6;4.47-fold),interleukin-6 receptor-α(IL-6Rα;5.74-fold)and glycoprotein 130(gp130;4.47-fold)in prostatic tissue.P.g-LPS could significantly inhibit cell apoptosis,promote mitosis and proliferation of cells.P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex,which destroys the imbalance between proliferation and apoptosis of prostate cells,induces BPH.Conclusion:P.gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis.P.gingivalis infection can promote BPH,which may affect the progression of BPH via inflammation and the Akt signaling pathway.展开更多
Periodontal disease is a risk factor for many systemic diseases such as Alzheimer’s disease and adverse pregnancy outcomes.Cleft palate(CP),the most common congenital craniofacial defect,has a multifaceted etiology i...Periodontal disease is a risk factor for many systemic diseases such as Alzheimer’s disease and adverse pregnancy outcomes.Cleft palate(CP),the most common congenital craniofacial defect,has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection.A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring.However,the precise relationship remains unclear.In this study,the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P.gingivalis injected intravenously and orally into pregnant mice.We investigated an obvious increasing CP(12.5%)in sonicated P.gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium.Then glycolysis and H4K12 lactylation(H4K12la)were detected to elevate in both mouse embryonic palatal mesenchyme(MEPM)cells and macrophages under P.gingivalis exposure which further promoted the transcription of metallopeptidase domain17(ADAM17),subsequently mediated the shedding of transforming growth factor-beta receptor 1(TGFBR1)in MEPM cells and mer tyrosine kinase(MerTK)in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate,eventually caused abnormalities in palate fusion and ossification.The abnormal efferocytosis also led to a predominance of M1 macrophages,which indirectly inhibited palatal osteogenesis via extracellular vesicles.Furthermore,pharmacological ADAM17 inhibition could ameliorate the abnormality of P.gingivalis-induced abnormal palate development.Therefore,our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.展开更多
基金supported by the National Natural Science Foundation of China(grant#82370975 and 82170969)。
文摘Cancer stem cells(CSCs)are widely acknowledged as primary mediators to the initiation and progression of tumors.The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years.Porphyromonas gingivalis(P.gingivalis)is increasingly considered to be closely related to the development of oral squamous cell carcinoma(OSCC).Nevertheless,the role of P.gingivalis in the stemness of OSCC cells remains uncertain.Herein,we showed that P.gingivalis was positively correlated with CSC markers expression in human OSCC specimens,promoted the stemness and tumorigenicity of OSCC cells,and enhanced tumor formation in nude mice.Mechanistically,P.gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1(SCD1)expression,a key enzyme involved in lipid metabolism,which ultimately resulted in enhanced acquisition of stemness.Moreover,SCD1 suppression attenuated P.gingivalis-induced stemness of OSCC cells,including CSCs markers expression,sphere formation ability,chemoresistance,and tumor growth,in OSCC cells both in vitro and in vivo.Additionally,upregulation of SCD1 in P.gingivalis-infected OSCC cells was associated with the expression of KLF5,and that was modulated by P.gingivalis-activated NOD1 signaling.Taken together,these findings highlight the importance of SCD1-dependent lipid synthesis in P.gingivalis-induced stemness acquisition in OSCC cells,suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.
基金supported(in part)by the National Natural Science Foundation of China(82200862,82370778)the Hubei Provincial Natural Science Foundation(2022CFB681,2023AFA061,2019CFB760)+4 种基金the Hubei Province Health and Family Planning Scientific Research Project(WJ2023M058,WJ2019H035)the Key Scientific Research Project of Education Department of Henan Province(22A320038)the Fundamental Research Funds for the Central Universities(2042023kf1019,2042023kf0051,2042022kf0072)the Zhongnan Hospital of Wuhan University,Science Technology and Innovation Seed Fund(CXPY2022074)the Young Top-notch Talent Cultivation Program of Hubei Province(for Prof.Zeng XT).
文摘Background:Benign prostatic hyperplasia(BPH)is the most common disease in elderly men.There is increasing evidence that periodontitis increases the risk of BPH,but the specific mechanism remains unclear.This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis(P.gingivalis)in the development of BPH.Methods:The subgingival plaque(Sp)and prostatic fluid(Pf)of patients with BPH concurrent periodontitis were extracted and cultured for 16S r DNA sequencing.Ligature-induced periodontitis,testosterone-induced BPH and the composite models in rats were established.The P.gingivalis and its toxic factor P.gingivalis lipopolysaccharide(P.gLPS)were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate.P.g-LPS was used to construct the prostate cell infection model for mechanism exploration.Results:P.gingivalis,Streptococcus oralis,Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Sp and Pf of patients with BPH concurrent periodontitis,and the average relative abundance of P.gingivalis was found to be the highest.P.gingivalis was detected in both Sp and Pf in 62.5%of patients.Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes.P.gingivalis and P.gLPS infection could induce obvious hyperplasia of the prostate epithelium and stroma(epithelial thickness was 2.97-fold and 3.08-fold that of control group,respectively),and increase of collagen fibrosis(3.81-fold and 5.02-fold that of control group,respectively).P.gingivalis infection promoted prostate cell proliferation,inhibited apoptosis,and upregulated the expression of inflammatory cytokines interleukin-6(IL-6;4.47-fold),interleukin-6 receptor-α(IL-6Rα;5.74-fold)and glycoprotein 130(gp130;4.47-fold)in prostatic tissue.P.g-LPS could significantly inhibit cell apoptosis,promote mitosis and proliferation of cells.P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex,which destroys the imbalance between proliferation and apoptosis of prostate cells,induces BPH.Conclusion:P.gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis.P.gingivalis infection can promote BPH,which may affect the progression of BPH via inflammation and the Akt signaling pathway.
基金funded by grants from the National Natural Science Foundation of China(grant numbers 82170912 and 82370910)the Beijing Stomatological Hospital,Capital Medical University Young Scientist Program(No.YSP202404).
文摘Periodontal disease is a risk factor for many systemic diseases such as Alzheimer’s disease and adverse pregnancy outcomes.Cleft palate(CP),the most common congenital craniofacial defect,has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection.A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring.However,the precise relationship remains unclear.In this study,the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P.gingivalis injected intravenously and orally into pregnant mice.We investigated an obvious increasing CP(12.5%)in sonicated P.gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium.Then glycolysis and H4K12 lactylation(H4K12la)were detected to elevate in both mouse embryonic palatal mesenchyme(MEPM)cells and macrophages under P.gingivalis exposure which further promoted the transcription of metallopeptidase domain17(ADAM17),subsequently mediated the shedding of transforming growth factor-beta receptor 1(TGFBR1)in MEPM cells and mer tyrosine kinase(MerTK)in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate,eventually caused abnormalities in palate fusion and ossification.The abnormal efferocytosis also led to a predominance of M1 macrophages,which indirectly inhibited palatal osteogenesis via extracellular vesicles.Furthermore,pharmacological ADAM17 inhibition could ameliorate the abnormality of P.gingivalis-induced abnormal palate development.Therefore,our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.
