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 Inflammatory bowel disease is a significant health concern for both humans and large-scale farm animals.In the quest for effective alternatives to antibiotics,next-generation probiotics(NGPs)have emerged as...Background Inflammatory bowel disease is a significant health concern for both humans and large-scale farm animals.In the quest for effective alternatives to antibiotics,next-generation probiotics(NGPs)have emerged as a promising option.The genus Blautia presents a rich source of potential NGP strains.Here we successfully isolated Blautia hominis LYH1 strain from the intestines of healthy weaned piglets and characterized its biological traits.Its antiinflammatory activity was then assessed using macrophages,while its protective effects against colitis and gut barrier damage were validated in a DSS-induced mouse colitis model.Results B.hominis LYH1 displayed typical characteristics of an obligate anaerobe,including non-hemolytic and nonmotile features,and a genome enriched with carbohydrate-active enzyme genes.It produced metabolites with antibiotic-like compounds,demonstrating antimicrobial activity against Escherichia coli.In vitro,B.hominis LYH1 effectively inhibited pathogen replication in macrophages,reducing cellular infections and alleviating inflammatory damage.In vivo,oral administration of B.hominis LYH1 or its metabolites significantly mitigated DSS-induced colitis in mice by suppressing pro-inflammatory cytokines,inhibiting T-lymphocyte activation,and enhancing short-chain fatty acid production.Conclusions Our findings underscore B.hominis LYH1’s potential as a NGP for maintaining gut health and combating intestinal inflammation.These findings offer valuable insights into the development of antibiotic alternatives and innovative strategies for preventing and treating enteritis in both agricultural and medical settings.展开更多
Abstract:Ulcerative Colitis(UC)has been reported to be related to Porphyromonas gingivalis(P.gingivalis).Porphyromonas gingivalis peptidylarginine deiminase(PPAD),a virulence factor released by P.gingivalis,is known t...Abstract:Ulcerative Colitis(UC)has been reported to be related to Porphyromonas gingivalis(P.gingivalis).Porphyromonas gingivalis peptidylarginine deiminase(PPAD),a virulence factor released by P.gingivalis,is known to induce inflammatory responses.To explore the pathological relationships between PPAD and UC,we used homologous recombination technology to construct a P.gingivalis strain in which the PPAD gene was deleted(Δppad)and aΔppad strain in which the PPAD gene was restored(comΔppad).C57 BL/6 mice were orally gavaged with saline,P.gingivalis,Δppad,or comΔppad twice a week for the entire 40 days(days 0-40),and then,UC was induced by dextran sodium sulfate(DSS)solution for 10 days(days 31-40).P.gingivalis and comΔppad exacerbated DDS-induced colitis,which was determined by assessing the parameters of colon length,disease activity index,and histological activity index,butΔppad failed to exacerbate DDS-induced colitis.Flow cytometry and ELISA revealed that compared withΔppad,P.gingivalis,and comΔppad increased T helper 17(Th17)cell numbers and interleukin(IL)-17 production but decreased regulatory T cells(Tregs)numbers and IL-10 production in the spleens of mice with UC.We also cocultured P.gingivalis,Δppad,or comΔppad with T lymphocytes in vitro and found that P.gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers.Immunofluorescence staining of colon tissue paraffin sections also confirmed these results.The results suggested that P.gingivalis exacerbated the severity of UC in part via PPAD.展开更多
Unlike other parts of the body, jaw defection often involves dental and periodontal tissues, which colonized a great many oral anaerobic bacteria. As a remarkable degradable material, magnesium has become an excellent...Unlike other parts of the body, jaw defection often involves dental and periodontal tissues, which colonized a great many oral anaerobic bacteria. As a remarkable degradable material, magnesium has become an excellent candidate for orthopedic appliances recently. But the high degradation rate is still a big problem. Making a biodegradable coating with good biocompatibility to slow down the degeneration rate of magnesium is one of the best methods. However, protective coatings will impair the antibacterial effects of magnesium which is caused by the rise of p H value throughout its degradation. To solve this problem, a series of composite coatings with different amounts of Cu O particles(3, 5 and 7 wt.%) were fabricated on pure magnesium through plasma electrolytic oxidation(PEO) to investigate in vitro biocompatibility and the antibacterial abilities against Porphyromonas gingivalis(P. gingivalis). Surface characterization and degradation behavior of the copper-bearing PEO coatings were also systematically studied. Furthermore,the most optimum coating was also systematically studied by X-ray photoelectron spectroscopy(XPS)and electrochemical corrosion test. Results of the present research revealed that adding proper amount of Cu O into PEO coatings could greatly improve the antibacterial abilities of the PEO coatings. The antibacterial activities of copper-bearing PEO coatings were excellent and revealed concentration-dependent and time-dependent. Biocompatibility of copper-bearing PEO coatings showed that proper amount of Cu could promote cell proliferation. Compared with other PEO coatings in this study, PEO-7 Cu showed some inhibition effects on cell proliferation and adhesion for long-term use. Electrochemical corrosion tests and immersion tests showed that PEO-5 Cu and PEO-7 Cu copper-bearing PEO coatings would provide satisfying corrosion resistance effects, while PEO-3 Cu was poorer than PEO coatings without Cu. However, compared with uncoated pure magnesium, the corrosion resistance of the PEO coating was much better. Based on the results of antibacterial ability, biocompatibility, and corrosion resistance of the above copper-bearing PEO coatings, PEO-5 Cu in this research was recommended to be used in patients with jaw defects.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 by Natural Science Foundation of Sichuan Province(2023NSFSC0237)National Natural Science Foundation of China(32372900)Major Special Projects in Sichuan Province(2021ZDZX0009).
文摘Background Inflammatory bowel disease is a significant health concern for both humans and large-scale farm animals.In the quest for effective alternatives to antibiotics,next-generation probiotics(NGPs)have emerged as a promising option.The genus Blautia presents a rich source of potential NGP strains.Here we successfully isolated Blautia hominis LYH1 strain from the intestines of healthy weaned piglets and characterized its biological traits.Its antiinflammatory activity was then assessed using macrophages,while its protective effects against colitis and gut barrier damage were validated in a DSS-induced mouse colitis model.Results B.hominis LYH1 displayed typical characteristics of an obligate anaerobe,including non-hemolytic and nonmotile features,and a genome enriched with carbohydrate-active enzyme genes.It produced metabolites with antibiotic-like compounds,demonstrating antimicrobial activity against Escherichia coli.In vitro,B.hominis LYH1 effectively inhibited pathogen replication in macrophages,reducing cellular infections and alleviating inflammatory damage.In vivo,oral administration of B.hominis LYH1 or its metabolites significantly mitigated DSS-induced colitis in mice by suppressing pro-inflammatory cytokines,inhibiting T-lymphocyte activation,and enhancing short-chain fatty acid production.Conclusions Our findings underscore B.hominis LYH1’s potential as a NGP for maintaining gut health and combating intestinal inflammation.These findings offer valuable insights into the development of antibiotic alternatives and innovative strategies for preventing and treating enteritis in both agricultural and medical settings.
基金supported by grants from the National Natural Science Foundation of China(81870771)the plan of the talents for Liaoning development(XLYC1802129)。
文摘Abstract:Ulcerative Colitis(UC)has been reported to be related to Porphyromonas gingivalis(P.gingivalis).Porphyromonas gingivalis peptidylarginine deiminase(PPAD),a virulence factor released by P.gingivalis,is known to induce inflammatory responses.To explore the pathological relationships between PPAD and UC,we used homologous recombination technology to construct a P.gingivalis strain in which the PPAD gene was deleted(Δppad)and aΔppad strain in which the PPAD gene was restored(comΔppad).C57 BL/6 mice were orally gavaged with saline,P.gingivalis,Δppad,or comΔppad twice a week for the entire 40 days(days 0-40),and then,UC was induced by dextran sodium sulfate(DSS)solution for 10 days(days 31-40).P.gingivalis and comΔppad exacerbated DDS-induced colitis,which was determined by assessing the parameters of colon length,disease activity index,and histological activity index,butΔppad failed to exacerbate DDS-induced colitis.Flow cytometry and ELISA revealed that compared withΔppad,P.gingivalis,and comΔppad increased T helper 17(Th17)cell numbers and interleukin(IL)-17 production but decreased regulatory T cells(Tregs)numbers and IL-10 production in the spleens of mice with UC.We also cocultured P.gingivalis,Δppad,or comΔppad with T lymphocytes in vitro and found that P.gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers.Immunofluorescence staining of colon tissue paraffin sections also confirmed these results.The results suggested that P.gingivalis exacerbated the severity of UC in part via PPAD.
基金financially supported by the National Natural Science Foundation of China(No.U1737102)the Shenyang Key R&D and Technology Transfer Program(No.Z18-0-027)+1 种基金the Shenyang Science and Technology Program(No.19-112-4-029)the Fundamental Research Funds for the Central Universities(N181903009and N2002009)。
文摘Unlike other parts of the body, jaw defection often involves dental and periodontal tissues, which colonized a great many oral anaerobic bacteria. As a remarkable degradable material, magnesium has become an excellent candidate for orthopedic appliances recently. But the high degradation rate is still a big problem. Making a biodegradable coating with good biocompatibility to slow down the degeneration rate of magnesium is one of the best methods. However, protective coatings will impair the antibacterial effects of magnesium which is caused by the rise of p H value throughout its degradation. To solve this problem, a series of composite coatings with different amounts of Cu O particles(3, 5 and 7 wt.%) were fabricated on pure magnesium through plasma electrolytic oxidation(PEO) to investigate in vitro biocompatibility and the antibacterial abilities against Porphyromonas gingivalis(P. gingivalis). Surface characterization and degradation behavior of the copper-bearing PEO coatings were also systematically studied. Furthermore,the most optimum coating was also systematically studied by X-ray photoelectron spectroscopy(XPS)and electrochemical corrosion test. Results of the present research revealed that adding proper amount of Cu O into PEO coatings could greatly improve the antibacterial abilities of the PEO coatings. The antibacterial activities of copper-bearing PEO coatings were excellent and revealed concentration-dependent and time-dependent. Biocompatibility of copper-bearing PEO coatings showed that proper amount of Cu could promote cell proliferation. Compared with other PEO coatings in this study, PEO-7 Cu showed some inhibition effects on cell proliferation and adhesion for long-term use. Electrochemical corrosion tests and immersion tests showed that PEO-5 Cu and PEO-7 Cu copper-bearing PEO coatings would provide satisfying corrosion resistance effects, while PEO-3 Cu was poorer than PEO coatings without Cu. However, compared with uncoated pure magnesium, the corrosion resistance of the PEO coating was much better. Based on the results of antibacterial ability, biocompatibility, and corrosion resistance of the above copper-bearing PEO coatings, PEO-5 Cu in this research was recommended to be used in patients with jaw defects.
