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Metformin is widely used as a first-line therapy for type 2 diabetes mellitus. However, the molecular mechanisms by which it modulates intestinal glucose metabolism remain incompletely defined. Here metformin was orally administered to male C57BL/6 mice, followed by intraperitoneal glucose tolerance testing and fluorine-18 fluorodeoxyglucose tracing to evaluate glucose homeostasis. To investigate changes in intestinal glucose metabolism, IEC6 and Caco-2 cell lines were used for in vitro analysis, with organoid experiments conducted for further validation. qRT-PCR, western blotting, flow cytometry and immunohistochemistry were performed to elucidate the effects of metformin on glucose metabolism pathways. Metformin enhanced glucose uptake and excretion in the distal intestine, particularly in the ileum and colon. Mechanistically, metformin upregulated the expression and membrane localization of glucose transporter 1 (GLUT1) by downregulating thioredoxin-interacting protein (TXNIP) expression. Consistently, intestinal-specific overexpression of TXNIP abolished metformin-induced improvements in glucose tolerance, while pharmacological inhibition of GLUT1 similarly negated metformin’s glucose-lowering effects. Our findings identified intestinal glucose excretion, mediated through the intestinal TXNIP–GLUT1 regulatory axis, as a previously unrecognized contributor to metformin’s glucoregulatory action. These results highlight a novel intestinal mechanism underlying metformin’s efficacy and provide insights for potential therapeutic strategies beyond traditional glucose regulation. New insights into metformin’s role in glucose metabolism Type 2 diabetes is a common health issue, and metformin is a widely used medication to manage it. Researchers explored how metformin affects glucose handling in the intestines. The researchers gave metformin to mice and observed increased glucose uptake and excretion in the intestines, particularly in the ileum and colon. They found that metformin enhances the activity of a protein called GLUT1, which helps transport glucose across cell membranes. This effect was linked to a decrease in another protein, TXNIP, which usually inhibits GLUT1. The study showed that metformin’s ability to lower blood sugar involves increasing GLUT1 activity by reducing TXNIP levels. This mechanism does not rely on AMPK (a protein involved in energy regulation), suggesting a new pathway for metformin’s action. These findings could lead to better diabetes treatments by targeting the intestinal TXNIP–GLUT1 pathway. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

Intestinal glucose excretion, defined as increased intestinal serum glucose uptake and secretion into the lumen, influences bariatric surgery-associated glycaemic control. Here, we investigate molecular mechanisms that activate intestinal glucose excretion. We evaluate altered transcriptomes in variable intestinal glucose excretion models and big data-based drug discovery systems. We show that protein kinase C (PKC) activation mimics transcriptome alterations observed during intestinal glucose excretion. Among PKC subfamilies, atypical PKC (aPKC) facilitates glucose transporter 1 (GLUT1)-mediated intestinal glucose excretion without inducing oncogenic proliferation. Intestinal aPKC activation via transposon expression vector induces serum glucose uptake into intestinal tissues and excretion into the lumen. Prostratin, a non-tumorigenic phorbol ester, activates aPKC and induces a similar effect on intestinal glucose excretion. We identify the prostratin and aPKC/GLUT1 signalling pathways as putative targets for treating diabetes, providing insights into the future development of antidiabetic and weight-loss drugs. Intestinal glucose excretion is a gut-based mechanism contributing to improved glycemic control after weight-loss surgery. Here, the authors describe a signaling pathway that drives intestinal glucose uptake and luminal excretion, identifying a potential therapeutic target for diabetes and weight loss.

The emergence of multidrug-resistant Shiga toxin-producing Escherichia coli (STEC) poses a major challenge to public health and necessitates the development of alternative antimicrobial strategies. This study aimed to isolate and characterize five lytic bacteriophages belonging to the genus Mosigvirus and evaluate their potential as biocontrol against MDR STEC strains and their biofilms. The five bacteriophages, designated vB_EcoM-pJBB (ΦB), vB_EcoM-pJBC (ΦC), vB_EcoM-pJBJ (ΦJ), vB_EcoM-pJBK (ΦK), and vB_EcoM-pJBL (ΦL), were isolated from sewage treatment plant samples using STEC ATCC 43895 as host. Biological characterization included host range determination against 19 MDR STEC strains, one-step growth analysis, environmental stability assays, bacteriolytic activity assessment, and antibiofilm efficacy testing. Whole-genome sequencing and phylogenetic analyses were performed to determine genomic features and taxonomic classification. The phages demonstrated varying infectious capacities, lysing between six and 12 strains, with ΦL exhibiting the broadest spectrum of activity. All phages showed MOI-independent antibiofilm activity, preventing biofilm formation by approximately 70% and disrupting pre-formed biofilms by up to 80.3%. Genomic analysis revealed the absence of lysogeny markers, virulence factors, and antimicrobial resistance genes, while identifying putative depolymerase genes associated with tail fiber proteins. Phylogenetic analysis confirmed the taxonomic position of these phages within the Mosigvirus genus in the Straboviridae family. Our findings indicate that the newly identified Mosigvirus phages are promising candidates for phage-based biocontrol applications.

Acute hepatopancreatic necrosis disease (AHPND) is one of the most important diseases in the global shrimp industry. The emergence of mutant AHPND-associated V. parahaemolyticus (VpAHPND) strains has raised concerns regarding potential misdiagnosis and unforeseen pathogenicity. In this study, we report the first emergence of a type II (pirA−, pirB+) natural mutant, VpAHPND (strain 20-082A3), isolated from cultured Penaeus vannamei in Korea. Phenotypic and genetic analyses revealed a close relationship between the mutant strain 20-082A3 and the virulent Korean VpAHPND strain 19-021-D1, which caused an outbreak in 2019. Detailed sequence analysis of AHPND-associated plasmids showed that plasmid pVp_20-082A3B in strain 20-082A3 was almost identical (>99.9%) to that of strain 19-021-D1. Moreover, strains 20-082A3 and 19-021-D1 exhibited the same multilocus sequence type (ST 413) and serotype (O1:Un-typeable K-serogroup), suggesting that the mutant strain is closely related to and may have originated from the virulent strain 19-021-D1. Similar to previous reports on the natural mutant VpAHPND, strain 20-082A3 did not induce AHPND-related symptoms or cause mortality in the shrimp bioassay. The emergence of a mutant strain which is almost identical to the virulent VpAHPND highlights the need for surveillance of the pathogen prevalent in Korea. Further investigations to elucidate the potential relationship between ST 413 and recent Korean VpAHPND isolates are needed.

Shiga toxin-producing Escherichia coli (STEC) infections have increased in humans, animals, and the food industry, with ready-to-eat (RTE) food products being particularly susceptible to contamination. The prevalence of multidrug-resistant strains has rendered the current control strategies insufficient to effectively control STEC infections. Herein, we characterized the newly isolated STEC phage vB_ESM-pEJ01, a polyvalent phage capable of infecting Escherichia and Salmonella species, and assessed its efficacy in reducing STEC in vitro and food matrices. The phage, belonging to the Tevenvirinae, exhibits effective bacteriolytic activity, a short latent period, large burst size, and stability under a broad pH range and moderate temperatures. Moreover, the phage demonstrated strong anti-biofilm efficacy even at low concentrations. Genomic analysis revealed that the phage was similar to the well-characterized RB49 phage (T4-like phage) but possesses distinct host-specificity-related genes that potentially contribute to its extensive host range. The efficacy of phage vB_ESM-pEJ01 was evaluated in artificially STEC-inoculated green juice samples, where it significantly reduced STEC and the abundance of Shiga toxin-producing genes at 4 and 25 °C. Therefore, these results suggest that the polyvalent phage vB_ESM-pEJ01 is a promising biocontrol agent for foodborne pathogens in RTE foods such as fresh juices.

We aimed to compare the molecular mechanisms and metabolic outcomes of Roux-en-Y gastric bypass (RYGB) and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) using a preclinical model. Otsuka Long-Evans Tokushima Fatty rats with diet-induced obesity underwent RYGB, SADI-S, or sham surgery. Metabolic parameters, including glucose tolerance, body weight, and 18F-fluorodeoxyglucose biodistribution, were assessed at 1- and 2-month postsurgery. The expression of Glucose transporter 1 (GLUT1) and glucose metabolism-related genes in intestinal segments was analyzed. Although RYGB and SADI-S yielded comparable improvements in glucose tolerance and body weight at 1 month postsurgery, they exerted their effects through distinct mechanisms. RYGB enhanced GLUT1-mediated glucose excretion in the common limb, whereas SADI-S upregulated the expression of the glycolytic genes and in the colon. Two months postsurgery, the observed metabolic improvements diminished despite sustained weight loss, which coincided with decreased expression of GLUT1 and glycolytic genes. RYGB and SADI-S achieve similar benefits through distinct glucose handling pathways; however, these effects decline over time. Our data do not support the superiority of SADI-S over RYGB, particularly given its higher complication rate, and instead highlight the need for strategies aimed at prolonging the therapeutic benefits of metabolic surgeries.

subsp. (PDD) is an emerging marine bacterial pathogen that infects marine animals and humans, causing fatal necrotizing fasciitis and histamine fish poisoning. Despite its clinical and ecological importance, the microbiological and genomic characteristics of PDD remain largely unknown. We report the first case of systemic infection caused by PDD in a free-ranging spotted seal ( ) stranded in Korea. Histopathological and microbial examinations were performed, followed by genomic analysis of the isolated PDD strain GCUPdd. Histamine production capability and cytotoxic effects on human cells were also evaluated. PDD was identified as the presumptive cause of systemic infection in the seal. Genomic analysis revealed the presence of pPHDD-like plasmid and major virulence factors including damselysin, phobalysin, and phospholipase. Strain GCUPdd harbored a gene cluster for histamine production (histidyl-tRNA synthetase, histidine decarboxylase, and histidine-histamine antiporter) and exhibited significantly higher histamine-producing ability than the reference PDD strain. The strain also demonstrated cytotoxic effects on human cells. Although the pathogenic role of PDD in pinnipeds remains unclear, this study highlights its zoonotic potential and the importance of monitoring PDD in marine environments. Our findings contribute to understanding risk factors for histamine fish poisoning and provide insights into microbial diversity in marine mammals, emphasizing the need for further surveillance concerning PDD pathogenicity and role in public health.

Abstract Disclosure: Y. Kim: None. Introduction: Age-related decline in endocrine function has been associated with multiple physiological changes. However, aging-associated molecular shifts in the pituitary gland have not yet been systematically investigated. This study aimed to investigate the mechanism underlying these age-related molecular changes in young and old mice model using single cell transcriptomics. Method: Single-cell RNA sequencing (scRNA-seq) were conducted in young (2-month) and old (20-month) mouse. We used systems biology techniques to build a specific protein interaction network for somatotrophs, integrating validated interactions and gene expression data. By simulating drug effects on this network, we predicted changes in transcription factor activities due to aging. We identified potential therapeutic targets for preventing aging in somatotrophs by assessing the anti-aging effects of chemical perturbations, similar to methods used in the Connectivity Map project. Results: We identified 14 distinct cell types including follicular stellate cells (FSCs), somatotrophs, corticotrophs, gonadotrophs, lactotrophs, and melanotrophs. We found that the effect of aging on transcription was cell type dependent. FSC subtypes are heterogeneously regulated by aging at the transcriptomic level. However, somatotroph subtypes shared functional alterations with aging in terms of mRNA surveillance and spliceosome pathways. Our systems biology approach identified SENP1(Sentrin specific peptidase gene), as a critical node in the regulatory network affecting somatotroph aging. The senescence-associated beta-galactosidase staining (SAbgal) showed that Momordin (Mc), a SENP1 inhibitor, had anti-aging effects on somatotrophs, regardless of age-promoting doxorubicin. Western blot analysis indicated a two-fold increase in growth hormone levels in aged GH3 cells treated with Mc compared to vehicle. Conclusion: Our data and analysis provide promising resources to better understand the molecular shifts of pituitary aging at the transcriptomic level and help the community generate interesting hypotheses to develop anti-aging strategies for the pituitary gland. We suggest that SENP1 inhibitors may represent potential anti-aging targets in somatotroph. Presentation: 6/3/2024

Although Streptococcus bovis/equinus complex (SBSEC) lysogens are prevalent in the rumen, studies on prophages experimentally induced from these strains are limited. Herein, we screened inducible prophages from ruminant-derived SBSEC strains, including the newly reported S. ruminicola, leading to the characterization of a representative temperate phage. We successfully induced a temperate phage (vB_SbS-proRumen) from S. ruminicola KCCM 90354, which has a broad host range, capable of lysing several SBSEC strains and other lactic acid bacteria. The vB_SbS-proRumen belongs to the Siphovirus, characterized by a short latent period, high burst size, and stability across pH and temperature conditions typical of subacute ruminal acidosis. The phage also demonstrates potent anti-biofilm activity. The vB_SbS-proRumen has a 38,092 bp double-stranded DNA genome with 58 predicted open reading frames, sharing high similarity and conserved genetic organization with other previously predicted SBSEC prophages. This study provides valuable insights into the diversity and plasticity of SBSEC phages.