Effect of inosine monophosphate dehydrogenase-1 gene polymorphisms on mycophenolate mofetil effectiveness in neuromyelitis optica spectrum disorder patients.

BACKGROUND: Inosine monophosphate dehydrogenase-1 is the target of mycophenolate mofetil. This research investigated the association between the gene polymorphism of inosine monophosphate dehydrogenase-1 and effectiveness of mycophenolate mofetil therapy in neuromyelitis optica spectrum disorder patients. METHODS: Fifty-nine neuromyelitis optica spectrum disorder patients accepted Mycophenolate Mofetil therapy for 1 year at least were divided into two groups: relapsing (n=21) and non-relapsing (n=38). Four single-nucleotide polymorphisms (SNPs: rs2228075, rs2278294, rs2288550, and rs3793165) in the inosine monophosphate dehydrogenase-1 gene were detected. Then we analyzed the allelic frequencies and the genotypes of SNPs in two groups. RESULTS: The allelic frequency of rs2278294 distributed differently between the relapse and non-relapsing patients (P=0.03), while no significant difference found in rs2228075, rs2288550 and rs3793165 between two groups. The genotypes C/C, C/T and T/T of rs2278294 (P = 0.031) also distributed differently between the two groups. Logistic regression analysis (adjusted by optic neuritis) showed that compared to the wild genotype C/C, C/T genotype had a 9-fold protection against relapse (OR=0.111 (0.022-0.548)), and T/T genotype had a 6.7-fold protection against relapse (OR=0.149 (0.026-0.854)). CONCLUSION: Our study provides preliminary evidence that the genotype of rs2278294 is associated with the response of neuromyelitis optica spectrum disorder patients to mycophenolate mofetil therapy. And compared to wild allelic C, the mutation to T tended to respond better to MMF.

ICAM-1 deletion delays the repair process in aging diabetic mice.

BACKGROUND: The delayed repair process in the aging diabetic population is becoming an alarming public health concern. ICAM-1 plays an important role in orchestrating the repair process by mediating neutrophil recruitment and phagocytosis. However, little is known about the role of ICAM-1 in aging diabetic repair. METHODS: By causing injury in aging diabetic mice with ICAM-1 deletion (AD-ICAM-1-/-), we found that AD-ICAM-1-/- mice exhibited a delayed repair process with incomplete re-epithelialization and reduced angiogenesis. Additionally, high-throughput Illumina sequencing was performed to evaluate the microbiota of such mice. RESULTS: The results indicate that the microbiota of the AD-ICAM-1-/- injury site differed taxonomically at both the phylum and genus levels. Neutrophil recruitment and phagocytic function were also reduced in the AD-ICAM-1-/- group. Notably, major inflammatory biomarker expression was also detected in AD-ICAM-1-/- injured tissue. CONCLUSIONS: Overall, this study demonstrated that AD-ICAM-1-/- mice exhibit delayed repair. In addition, neutrophil recruitment and phagocytic activity were impaired in the AD-ICAM-1-/- group, which may have allowed microbes to colonize the injury site.

Glucorticoid-induced obesity individuals have distinct signatures of the gut microbiome.

The human intestine and its resident microbiota are known to play an essential role in the pathogenesis of primary obesity. However, a little is known of the gut microbiota profiles in individuals with obesity induced by glucocorticoid (GC) therapy. Here, we recruited 28 people with GC-induced obesity and 27 age- and gender-matched healthy controls, whose feces have been collected separately, to delineate the gut microbial characteristics in GC-induced obesity individuals. High-throughput Illumina sequencing targeting the V4 region of the 16S rRNA gene has been applied to analyze the structure of the intestinal microbiome. Gas chromatography was also used to measure levels of short-chain fatty acids (SCFAs), a subset of key gut microbial metabolites mainly produced by Bacteroidetes. We found dramatically decreased gut microbial diversity in individuals with GC-induced obesity. In addition, the bacterial communities of the GC-induced obesity group were enriched in Firmicutes (e.g., genus Streptococcus) and depleted in Bacteroidetes. Furthermore, SCFA content was decreased in GC-induced obesity status. Overall, this study conducted a case-control study with 55 participants in which we analyzed gut microbiota to develop intestinal microbial profiles of patients undergoing long-term treatment with GCs. Concomitantly, the level of SCFAs was also detected in those study participants.