BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.Howeve...BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.However,its specific molecular and biological mechanisms remain unclear.AIM To investigate the therapeutic effect and mechanism of modified PD in IM.METHODS This study used an IM mouse model established using 5-fluorouracil injections to investigate the effects of the modified PD(3,6,and 12 g/kg)in IM.The primary chemical components of the modified PD were identified using liquid chromatography-mass spectrometry.Body weight loss,diarrhea scores,intestinal length,histopathological scores,and inflammatory cytokine levels were measured to evaluate the effects of the modified PD in IM.Effects on the TLR4/MyD88/NF-κB pathway were evaluated using western blot analysis.The intestinal microbiota was characterized using Illumina NovaSeq sequencing.RESULTS The results showed that modified PD significantly improved weight loss and diarrhea and shortened the intestines in IM mice.Mechanistically,modified PD suppressed the TLR4/MyD88/NF-κB pathway and downregulated the expression of reactive oxygen species,lipopolysaccharides,and pro-inflammatory cytokines(IL-1β,TNF-α,IFN-γ,IL-6,IL-8,and IL-17),while increasing the expression of the anti-inflammatory cytokine IL-10.Furthermore,modified PD protected the intestinal mucosal barrier by increasing the expression of tight junction proteins(occludin-1,claudin-1,and ZO-1)and mucin-2.Finally,16S rDNA sequencing revealed that modified PD improved intestinal dysbiosis.CONCLUSION Our research offers new insights into the potential mechanism of modified PD in alleviating IM and provides experimental evidence supporting its pharmaceutical application in clinical IM treatment.展开更多
BackgroundIn the normal life cycle of the parasite(Echinococcus multilocularis)that causes alveolar echinococcosis,domestic and wild carnivores act as definitive hosts,and rodents act as intermediate hosts.The present...BackgroundIn the normal life cycle of the parasite(Echinococcus multilocularis)that causes alveolar echinococcosis,domestic and wild carnivores act as definitive hosts,and rodents act as intermediate hosts.The presented study contributes to the research on the distribution and transmission pattern of E.multilocularis in China having identified sheep as an unusual intermediate host taking part in the domestic transmission of alveolar echinococcosis in Gansu Province,China.MethodsFrom 2020 to 2021,nine whitish different cyst-like were collected from the liver of sheep in Gansu Province for examination.A near complete mitochondrial(mt)genome and selected nuclear genes were amplified from the cyst-like lesion for identification.To confirm the status of the specimen,comparative analysis with reference sequences,phylogenetic analysis,and network analysis were performed.ResultsThe isolates displayed≥98.87%similarity to E.multilocularis NADH dehydrogenase sub-unit 1(nad1)(894 bp)reference sequences deposited in GenBank.Furthermore,amplification of the nad4 and nad2 genes also confirmed all nine samples as E.multilocularis with>99.30%similarity.Additionally,three nuclear genes,pepck(1545 bp),elp-exons VII and VIII(566 bp),and elp-exon IX(256 bp),were successfully amplified and sequenced for one of the isolates with 98.42%similarity,confirming the isolates were correctly identified as E.multilocularis.Network analysis also correctly placed the isolates with other E.multilocularis.ConclusionsAs a result of the discovery of E.multilocularis in an unusual intermediate host,which is considered to have the highest zoonotic potential,the result clearly demonstrated the necessity for expanded surveillance in the area.展开更多
基金Supported by Basic and Applied Basic Research Foundation of Guangdong Province,No.2021B1515140043,No.2022A1515140124 and No.2023A1515140115.
文摘BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.However,its specific molecular and biological mechanisms remain unclear.AIM To investigate the therapeutic effect and mechanism of modified PD in IM.METHODS This study used an IM mouse model established using 5-fluorouracil injections to investigate the effects of the modified PD(3,6,and 12 g/kg)in IM.The primary chemical components of the modified PD were identified using liquid chromatography-mass spectrometry.Body weight loss,diarrhea scores,intestinal length,histopathological scores,and inflammatory cytokine levels were measured to evaluate the effects of the modified PD in IM.Effects on the TLR4/MyD88/NF-κB pathway were evaluated using western blot analysis.The intestinal microbiota was characterized using Illumina NovaSeq sequencing.RESULTS The results showed that modified PD significantly improved weight loss and diarrhea and shortened the intestines in IM mice.Mechanistically,modified PD suppressed the TLR4/MyD88/NF-κB pathway and downregulated the expression of reactive oxygen species,lipopolysaccharides,and pro-inflammatory cytokines(IL-1β,TNF-α,IFN-γ,IL-6,IL-8,and IL-17),while increasing the expression of the anti-inflammatory cytokine IL-10.Furthermore,modified PD protected the intestinal mucosal barrier by increasing the expression of tight junction proteins(occludin-1,claudin-1,and ZO-1)and mucin-2.Finally,16S rDNA sequencing revealed that modified PD improved intestinal dysbiosis.CONCLUSION Our research offers new insights into the potential mechanism of modified PD in alleviating IM and provides experimental evidence supporting its pharmaceutical application in clinical IM treatment.
文摘BackgroundIn the normal life cycle of the parasite(Echinococcus multilocularis)that causes alveolar echinococcosis,domestic and wild carnivores act as definitive hosts,and rodents act as intermediate hosts.The presented study contributes to the research on the distribution and transmission pattern of E.multilocularis in China having identified sheep as an unusual intermediate host taking part in the domestic transmission of alveolar echinococcosis in Gansu Province,China.MethodsFrom 2020 to 2021,nine whitish different cyst-like were collected from the liver of sheep in Gansu Province for examination.A near complete mitochondrial(mt)genome and selected nuclear genes were amplified from the cyst-like lesion for identification.To confirm the status of the specimen,comparative analysis with reference sequences,phylogenetic analysis,and network analysis were performed.ResultsThe isolates displayed≥98.87%similarity to E.multilocularis NADH dehydrogenase sub-unit 1(nad1)(894 bp)reference sequences deposited in GenBank.Furthermore,amplification of the nad4 and nad2 genes also confirmed all nine samples as E.multilocularis with>99.30%similarity.Additionally,three nuclear genes,pepck(1545 bp),elp-exons VII and VIII(566 bp),and elp-exon IX(256 bp),were successfully amplified and sequenced for one of the isolates with 98.42%similarity,confirming the isolates were correctly identified as E.multilocularis.Network analysis also correctly placed the isolates with other E.multilocularis.ConclusionsAs a result of the discovery of E.multilocularis in an unusual intermediate host,which is considered to have the highest zoonotic potential,the result clearly demonstrated the necessity for expanded surveillance in the area.
