CD4+CD25+Foxp3+ Tregs control the immune response and maintain immune homeostasis. This study examined whether Tregs can affect mouse enteritis and the Foxp3 (Forkhead transcription factor) transcriptional pathway. Mouse CD4+CD25+ Treg cells were labelled using CFSE (5,6-carboxyfluorescein diacetate succinimidyl ester) and transferred to enteritis model mice. The mice were randomly divided into an enteritis group, a Treg-infusion group, a Treg-inhibiting group, and a control group. Histopathology, ELISA, flow cytometry, western blot, immunohistochemistry, and immunofluorescence were performed. Our results demonstrated that CD4+CD25+ Tregs were successfully transferred. The disease activity index (DAI) scores in the Tregs-infusion group were lower than those of the enteritis and Tregs-inhibiting groups. The number of goblet cells and inflammatory cells was reduced, and the levels of IL-1β, TNF-α, NO, and PGE2 were significantly decreased in the Tregs-infusion group compared to those in the enteritis group (p<0.05). The number of CD4+CD25+Foxp3+ Tregs and CD4+IL-17A+ Th17 cells in the mesenteric lymph nodes differed significantly from the enteritis and Tregs-inhibiting groups (p<0.05). There were more Foxp3+ Tregs and Smad3 and NFAT2 infiltrated into the duodenum after adoptive transfer of CD4+CD25+ Tregs, which was a significant difference relative to the enteritis group (p<0.05). This study demonstrated that adoptive transfer of CD4+CD25+ Tregs can decrease mouse enteritis. Foxp3 expression may be improved through the Smad3 and NFAT2 signalling pathways.
Background:
Persistent high-risk genital human papillomavirus (HPV) infection is a major cause of cervical
cancer in women. The products of the viral transforming genes E6 and E7 in the high-risk HPVs are known to be similar
in their amino acid composition and structure. We performed a comparative analysis of codon usage patterns in the E6
and E7 genes of HPVs.
Methods:
The E6 and E7 gene sequences of eight HPV subtypes were analyzed to determine their nucleotide
composition, relative synonymous codon usage (RSCU), effective number of codons (ENC), neutrality, genetic
variability, selection pressure, and codon adaptation index (CAI). Additionally, a correspondence analysis (CoA) was
performed.
Results:
The analysis to determine the effects of differences in composition on the codon usage patterns revealed that
there may be usage bias for ‘A’ nucleotides. This was consistent with the results of the RSCU analysis, which
demonstrated that the selection of A/T-rich patterns and the preference for A/T-ended codons in HPVs are influenced by
compositional constraints. Moreover, the results reveal that selection pressure plays an important role in the CoA results
for the RSCU values, Tajima’s D tests, and neutrality tests.
Conclusion:
The results of this study are consistent with previous findings that most papillomavirus genes are under
purifying selection pressure, which limits changes to the encoded proteins. Natural selection and mutation pressures
resulting in changes in the nucleotide composition and codon usage bias in the two tumor genes of HPV act differently
during the evolution of the HPV subtype; thus, throughout the viral life cycle, HPV can constantly evolve to adapt to a
new environment.
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