Alterations in the intestinal microbial flora are known to cause various diseases, and many people routinely consume probiotics or prebiotics to balance intestinal microorganisms and the growth of beneficial bacteria. In this study, we selected a peptide from fish (tilapia) skin that induces significant changes in the intestinal microflora of mice and reduces the Firmicutes/Bacteroidetes ratio, which is linked to obesity. We attempted to verify the anti-obesity effect of selected fish collagen peptides in a high-fat-diet-based obese mouse model. As anticipated, the collagen peptide co-administered with a high-fat diet significantly inhibited the increase in the Firmicutes/Bacteroidetes ratio. It increased specific bacterial taxa, including Clostridium_sensu_stricto_1, Faecalibaculum, Bacteroides, and Streptococcus, known for their anti-obesity effects. Consequently, alterations in the gut microbiota resulted in the activation of metabolic pathways, such as polysaccharide degradation and essential amino acid synthesis, which are associated with obesity inhibition. In addition, collagen peptide also effectively reduced all obesity signs caused by a high-fat diet, such as abdominal fat accumulation, high blood glucose levels, and weight gain. Ingestion of collagen peptides derived from fish skin induced significant changes in the intestinal microflora and is a potential auxiliary therapeutic agent to suppress the onset of obesity.

Yeasts are very useful microorganisms that are used in many industrial fermentation processes such as food and alcohol production. Microbial contamination of such processes is inevitable, since most of the fermentation substrates are not sterile. Contamination can cause a reduction of the final product concentration and render industrial yeast strains unable to be reused. Alternative approaches to controlling contamination, including the use of antibiotics, have been developed and proposed as solutions. However, more efficient and industry-friendly approaches are needed for use in industrial applications. This review covers: (i) general information about industrial uses of yeast fermentation, (ii) microbial contamination and its effects on yeast fermentation, and (iii) currently used and suggested approaches/strategies for controlling microbial contamination at the industrial and/or laboratory scale.

O-linked β-N-acetylglucosamine (O-GlcNAc) modification regulates the activity of hundreds of nucleocytoplasmic proteins involved in a wide variety of cellular processes, such as gene expression, signaling, and cell growth; however, the mechanism underlying the regulation of B cell development and function by O-GlcNAcylation remains largely unknown. Here, we demonstrate that changes in cellular O-GlcNAc levels significantly affected the growth of pre-B cells, which rapidly proliferate to allow expansion of functional clones that express successfully rearranged heavy chains at the pro-B stage during early B cell development. In our study, the overall O-GlcNAc levels in these proliferative pre-B cells, which are linked to the glucose uptake rate, were highly induced when compared with those in pro-B cells. Thus, pharmacologically, genetically, or nutritionally, inhibition of O-GlcNAcylation in pre-B cells markedly downregulated c-Myc expression, resulting in cell cycle arrest via blockade of cyclin expression. Importantly, the population of B cells after the pro-B cell stage in mouse bone marrow was severely impaired by the administration of an O-GlcNAc inhibitor. These results strongly suggest that O-GlcNAcylation-dependent expression of c-Myc represents a new regulatory component of pre-B cell proliferation, as well as a potential therapeutic target for the treatment of pre-B cell-derived leukemia.

Shiga toxins (Stxs) produced by enterohemorrhagic Escherichia coli (EHEC) are the major virulence factors responsible for hemorrhagic colitis, which can lead to life‐threatening systemic complications including acute renal failure (hemolytic uremic syndrome) and neuropathy. Here, we report that O‐GlcNAcylation, a type of post‐translational modification, was acutely increased upon induction of endoplasmic reticulum (ER) stress in host cells by Stxs. Suppression of the abnormal Stx‐mediated increase in O‐GlcNAcylation effectively inhibited apoptotic and inflammatory responses in Stx‐susceptible cells. The protective effect of O‐GlcNAc inhibition for Stx‐mediated pathogenic responses was also verified using three‐dimensional (3D)‐cultured spheroids or organoids mimicking the human kidney. Treatment with an O‐GlcNAcylation inhibitor remarkably improved the major disease symptoms and survival rate for mice intraperitoneally injected with a lethal dose of Stx. In conclusion, this study elucidates O‐GlcNAcylation‐dependent pathogenic mechanisms of Stxs and demonstrates that inhibition of aberrant O‐GlcNAcylation is a potential approach to treat Stx‐mediated diseases.

Shiga toxins (Stxs) produced by Shiga toxin-producing bacteria Shigella dysenteriae serotype 1 and select serotypes of Escherichia coli are the most potent known virulence factors in the pathogenesis of hemorrhagic colitis progressing to potentially fatal systemic complications such as acute renal failure, blindness and neurological abnormalities. Although numerous studies have defined apoptotic responses to Shiga toxin type 1 (Stx1) or Shiga toxin type 2 (Stx2) in a variety of cell types, the potential significance of Stx-induced apoptosis of photoreceptor and pigmented cells of the eye following intoxication is unknown. We explored the use of immortalized human retinal pigment epithelial (RPE) cells as an in vitro model of Stx-induced retinal damage. To the best of our knowledge, this study is the first report that intoxication of RPE cells with Stxs activates both apoptotic cell death signaling and the endoplasmic reticulum (ER) stress response. Using live-cell imaging analysis, fluorescently labeled Stx1 or Stx2 were internalized and routed to the RPE cell endoplasmic reticulum. RPE cells were significantly sensitive to wild type Stxs by 72 h, while the cells survived challenge with enzymatically deficient mutant toxins (Stx1A⁻ or Stx2A⁻). Upon exposure to purified Stxs, RPE cells showed activation of a caspase-dependent apoptotic program involving a reduction of mitochondrial transmembrane potential (Δψ_m), increased activation of ER stress sensors IRE1, PERK and ATF6, and overexpression CHOP and DR5. Finally, we demonstrated that treatment of RPE cells with Stxs resulted in the activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK), suggesting that the ribotoxic stress response may be triggered. Collectively, these data support the involvement of Stx-induced apoptosis in ocular complications of intoxication. The evaluation of apoptotic responses to Stxs by cells isolated from multiple organs may reveal unique functional patterns of the cytotoxic actions of these toxins in the systemic complications that follow ingestion of toxin-producing bacteria.

Host defense mechanisms against viral infections have been extensively studied over the past few decades and continue to be a crucial area of research in understanding human diseases caused by acute and chronic viral infections. Among various host mechanisms, recent findings have revealed that several host RNA-binding proteins play pivotal roles in regulating viral RNA to suppress viral replication and eliminate infection. We have focused on identifying host proteins that function as regulators of viral RNA, specifically targeting viral components without adversely affecting host cells. Interestingly, these proteins exhibit dual roles in either restricting viral infections or promoting viral persistence by interacting with cofactors to either degrade viral genomes or stabilize them. In this review, we discuss RNA-binding zinc finger proteins as viral RNA regulators, classified into two major types: ZCCCH-type and ZCCHC-type. By highlighting the functional diversity of these zinc finger proteins, this review provides insights into their potential as therapeutic targets for the development of novel antiviral therapies.