Investigating the crucial role of selected Bifidobacterium probiotic strains in preventing or reducing inflammation by affecting the autophagy pathway.

Several studies have shown that probiotics can prevent and reduce inflammation in inflammation-related diseases. However, few studies have focused on the interaction between host and probiotics in modulating the immune system through autophagy. Therefore, we aimed to investigate the preventive and/or therapeutic effects of native potential probiotic breast milk-isolated Bifidobacterium spp. (i.e. B. bifidum, B. longum, and B. infantis) on the inflammatory cascade by affecting autophagy gene expression 24 and 48 h after treatment. Autophagy genes involved in different stages of the autophagy process were selected by quantitative polymerase chain reaction (qPCR). Gene expression investigation was accomplished by exposing the human colorectal adenocarcinoma cell line (HT-29) to sonicated pathogens (1.5 × 108 bacterial CFU ml-1) and adding Bifidobacterium spp. (MOI10) before, after, and simultaneously with induction of inflammation. An equal volume of RPMI medium was used as a control. Generally, our native potential probiotic Bifidobacterium spp. can increase the autophagy gene expression in comparison with pathogen. Moreover, an increase in gene expression was observed with our probiotic strains' consumption in all stages of autophagy. Totally, our selected Bifidobacterium spp. can increase autophagy gene expression before, simultaneously, and after the inflammation induction, so they can prevent and reduce inflammation in an in vitro model of inflammation.

Q192R variant in paraoxonase 1 gene confers susceptibility to leiomyoma.

OBJECTIVE: Paraoxonase 1 (PON1) plays a defensive role against oxidative stress by destroying oxidized lipids. Q192R single nucleotide polymorphism of PON1 gene alters the enzyme's activity. Several investigations reported a link between Q192R and an increased risk of developing tumors including uterine leiomyomas. We assessed the antioxidant effects of Q192R on myoma which fluctuate in frequency between populations. STUDY DESIGN: The cohort consisted of 68 unrelated uterine leiomyoma patients and 93 healthy controls that were randomly selected from women with no ultrasonographic evidence of myoma. MATERIALS AND METHODS: Genotyping was performed using tetra-primer amplification refractory mutation system-polymerase chain reaction. Chi-square test was selected to evaluate differences between the groups. RESULTS: To analyze the correlation between PON1 Q192R and leiomyoma risk, the AA genotype was given as a reference genotype then the two other genotypes were compared with the reference. A significantly (P < 0.05) increased risk of myoma was observed with both Q192R homozygote GG and heterozygote AG genotypes. The odds ratio (OR) of AG genotype was calculated 1.8 (confidence interval [CI]: 0.94-3.62). A higher OR was seen with GG genotype (OR: 2.8; 95% CI: 0.98-8.18). CONCLUSION: Oxidative stress has been suspected of having a link with tumor development, and the role of endogenous-free radical scavenger is taken into consideration. Increased protein oxidative stress status and reduced antioxidant capacity have been observed in leiomyomas patients. Our study indicates that the low-antioxidant PON1 R192 allele correlates to leiomyoma development.

Identification of Differentially Expressed K-Ras Transcript Variants in Patients With Leiomyoma.

PURPOSE: Molecular studies have demonstrated a wide range of gene expression variations in uterine leiomyoma. The rat sarcoma virus/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase (RAS/RAF/MAPK) is the crucial cellular pathway in transmitting external signals into nucleus. Deregulation of this pathway contributes to excessive cell proliferation and tumorigenesis. The present study aims to investigate the expression profile of the K-Ras transcripts in tissue samples from patients with leiomyoma. METHODS: The patients were leiomyoma cases who had no mutation in mediator complex subunit 12 ( MED12) gene. A quantitative approach has been applied to determine the difference in the expression of the 2 main K-Ras messenger RNA (mRNA) variants. The comparison between gene expression levels in leiomyoma and normal myometrium group was performed using relative expression software tool. RESULTS: The expression of K-Ras4B gene was upregulated in leiomyoma group ( P = .016), suggesting the involvement of K-Ras4B in the disease pathogenesis. Pairwise comparison of the K-Ras4B expression between each leiomyoma tissue and its matched adjacent normal myometrium revealed gene upregulation in 68% of the cases. The expression of K-Ras4A mRNA was relatively upregulated in leiomyoma group ( P = .030). In addition, the mean expression of K-Ras4A gene in leiomyoma tissues relative to normal samples was 4.475 (95% confidence interval: 0.10-20.42; standard error: 0.53-12.67). In total, 58% of the cases showed more than 2-fold increase in K-Ras4A gene expression. CONCLUSION: Our results demonstrated increased expression of both K-Ras mRNA splicing variants in leiomyoma tissue. However, the ultimate result of KRAS expression on leiomyoma development depends on the overall KRAS isoform balance and, consequently, on activated signaling pathways.