Objective: To study the potential role of macrophage migration inhibitory factor (MIF), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the development of chronic virus hepatitis B (CH) and hepatitis cir...Objective: To study the potential role of macrophage migration inhibitory factor (MIF), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the development of chronic virus hepatitis B (CH) and hepatitis cirrhosis (HC). Methods: The serum concentrations of MIF, TNF-α and IL-6 in 18 patients with chronic virus hepatitis B and in 14 patients with hepatitis cirrhosis without as- citic fluid, and the serum and ascites cytokine con- centrations in 22 HC patients with ascitic fluid were detected by enzyme linked immunity sorbed assay. Results: The cytokine concentrations of the patients were significantly higher than those of the controls. The serum levels of MIF, TNF-α and IL-6 of the 22 patients with ascitic fluid were higer than those of 14 HC patients without ascites. In the 18 patients with CH, the serum cytokine concentrations were the low- est. The serum cytokine concentrations of the 22 HC patients with ascites were significantly higher than those of the 14 HC patients without ascites (P< 0. 01). Their serum cytokine concentrations were sig- nificantly higher than those in the 18 patients with CH (P<0. 01). The concentration of IL-6 in ascites was the highest among all the groups. The serum le- vels of MIF, TNF-α and IL-6 are correlated with al- anine aminotransferase (ALT) in the patients with CH, but not in those with HC with or without asci- tes. Conclusions: These results indicated that MIF, TNF- α and IL-6 may participate in the pathological process of CH and cirrhosis, that IL-6 seems to play an important role in ascites formation, and that se- rum levels of MIF, TNF-α and IL-6 appear to reflect the severity of tissue injury in HBV disease.展开更多
The rapid development of metagenomics,metabolomics,and metatranscriptomics provides novel insights into the intestinal microbiota factors linked to inflammatory bowel disease(IBD).Multiple microorganisms play a role i...The rapid development of metagenomics,metabolomics,and metatranscriptomics provides novel insights into the intestinal microbiota factors linked to inflammatory bowel disease(IBD).Multiple microorganisms play a role in intestinal health;these include bacteria,fungi,and viruses that exist in a dynamic balance to maintain mucosal homeostasis.Perturbations in the intestinal microbiota disrupt mucosal homeostasis and are closely related to IBD in humans and colitis in mice.Therefore,preventing or correcting the imbalance of microbiota may serve as a novel prevention or treatment strategy for IBD.We review the most recent evidence for direct or indirect interventions targeting intestinal microbiota for treatment of IBD in order to overcome the current limitations of IBD therapies and shed light on personalized treatment options.展开更多
Irinotecan(CPT11)chemotherapy-induced diarrhea affects a substantial cancer population due to b-glucuronidase(Gus)converting 10-O-glucuronyl-7-ethyl-10-hydroxycamptothecin(SN38G)to toxic 7-ethyl-10-hydroxycamptothecin...Irinotecan(CPT11)chemotherapy-induced diarrhea affects a substantial cancer population due to b-glucuronidase(Gus)converting 10-O-glucuronyl-7-ethyl-10-hydroxycamptothecin(SN38G)to toxic 7-ethyl-10-hydroxycamptothecin(SN38).Existing interventions primarily address inflammation and Gus enzyme inhibition,neglecting epithelial repair and Gus-expressing bacteria.Herein,we discov-ered that dehydrodiisoeugenol(DDIE),isolated from nutmeg,alleviates CPT11-induced intestinal muco-sitis alongside a synergistic antitumor effect with CPT11 by improving weight loss,colon shortening,epithelial barrier dysfunction,goblet cells and intestinal stem cells(ISCs)loss,and wound-healing.The anti-mucositis effect of DDIE is gut microbiota-dependent.Analysis of microbiome profiling data from clinical patients and CPT11-induced mucositis mice reveals a strong correlation between CPT11 chemotoxicity and Gus-expressing bacteria,particularly Enterococcus faecalis(E.faecalis).DDIE coun-ters CPT11-induced augmentation of E.faecalis,leading to decreased intestinal Gus and SN38 levels.The Partial Least Squares Path Model(PLS-PM)algorithm initially links E.faecalis to dysregulated epithelial renovation.This is further validated in a 3D intestinal organoid model,in which both SN38 and E.faecalis hinder the formation and differentiation of organoids.Interestingly,colonization of E.fae-calis exacerbates CPT11-induced mucositis and disturbs epithelial differentiation.Our study unveils a microbiota-driven,epithelial reconstruction-mediated action of DDIE against mucositis,proposing the‘Gus bacteriaehosteirinotecan axis’as a promising target for mitigating CPT11 chemotoxicity.展开更多
文摘Objective: To study the potential role of macrophage migration inhibitory factor (MIF), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the development of chronic virus hepatitis B (CH) and hepatitis cirrhosis (HC). Methods: The serum concentrations of MIF, TNF-α and IL-6 in 18 patients with chronic virus hepatitis B and in 14 patients with hepatitis cirrhosis without as- citic fluid, and the serum and ascites cytokine con- centrations in 22 HC patients with ascitic fluid were detected by enzyme linked immunity sorbed assay. Results: The cytokine concentrations of the patients were significantly higher than those of the controls. The serum levels of MIF, TNF-α and IL-6 of the 22 patients with ascitic fluid were higer than those of 14 HC patients without ascites. In the 18 patients with CH, the serum cytokine concentrations were the low- est. The serum cytokine concentrations of the 22 HC patients with ascites were significantly higher than those of the 14 HC patients without ascites (P< 0. 01). Their serum cytokine concentrations were sig- nificantly higher than those in the 18 patients with CH (P<0. 01). The concentration of IL-6 in ascites was the highest among all the groups. The serum le- vels of MIF, TNF-α and IL-6 are correlated with al- anine aminotransferase (ALT) in the patients with CH, but not in those with HC with or without asci- tes. Conclusions: These results indicated that MIF, TNF- α and IL-6 may participate in the pathological process of CH and cirrhosis, that IL-6 seems to play an important role in ascites formation, and that se- rum levels of MIF, TNF-α and IL-6 appear to reflect the severity of tissue injury in HBV disease.
基金Supported by National Natural Science Foundation of China,No.81273572 and No.81530096the Natural Science Foundation of Shanghai,No.17ZR1427800.
文摘The rapid development of metagenomics,metabolomics,and metatranscriptomics provides novel insights into the intestinal microbiota factors linked to inflammatory bowel disease(IBD).Multiple microorganisms play a role in intestinal health;these include bacteria,fungi,and viruses that exist in a dynamic balance to maintain mucosal homeostasis.Perturbations in the intestinal microbiota disrupt mucosal homeostasis and are closely related to IBD in humans and colitis in mice.Therefore,preventing or correcting the imbalance of microbiota may serve as a novel prevention or treatment strategy for IBD.We review the most recent evidence for direct or indirect interventions targeting intestinal microbiota for treatment of IBD in order to overcome the current limitations of IBD therapies and shed light on personalized treatment options.
基金supported by the National Natural Science Foundation of China(No.82274329,82304991,82130115)the China Postdoctoral Science Foundation(No.2023M732336)the Shanghai Science and Technology Committee Sailing Program Foundation(No.23YF1442500,China).
文摘Irinotecan(CPT11)chemotherapy-induced diarrhea affects a substantial cancer population due to b-glucuronidase(Gus)converting 10-O-glucuronyl-7-ethyl-10-hydroxycamptothecin(SN38G)to toxic 7-ethyl-10-hydroxycamptothecin(SN38).Existing interventions primarily address inflammation and Gus enzyme inhibition,neglecting epithelial repair and Gus-expressing bacteria.Herein,we discov-ered that dehydrodiisoeugenol(DDIE),isolated from nutmeg,alleviates CPT11-induced intestinal muco-sitis alongside a synergistic antitumor effect with CPT11 by improving weight loss,colon shortening,epithelial barrier dysfunction,goblet cells and intestinal stem cells(ISCs)loss,and wound-healing.The anti-mucositis effect of DDIE is gut microbiota-dependent.Analysis of microbiome profiling data from clinical patients and CPT11-induced mucositis mice reveals a strong correlation between CPT11 chemotoxicity and Gus-expressing bacteria,particularly Enterococcus faecalis(E.faecalis).DDIE coun-ters CPT11-induced augmentation of E.faecalis,leading to decreased intestinal Gus and SN38 levels.The Partial Least Squares Path Model(PLS-PM)algorithm initially links E.faecalis to dysregulated epithelial renovation.This is further validated in a 3D intestinal organoid model,in which both SN38 and E.faecalis hinder the formation and differentiation of organoids.Interestingly,colonization of E.fae-calis exacerbates CPT11-induced mucositis and disturbs epithelial differentiation.Our study unveils a microbiota-driven,epithelial reconstruction-mediated action of DDIE against mucositis,proposing the‘Gus bacteriaehosteirinotecan axis’as a promising target for mitigating CPT11 chemotoxicity.
