Dysfunction of the Murine Liver with Aging and Its Improvement with the Continuous Consumption of Enterococcus faecalis EC-12.

Chronic inflammation is involved in the development of age-related diseases. Given its persistence, controlling chronic inflammation is essential for preventing age-related diseases. In this study, we investigated the effects of Enterococcus faecalis EC-12 (EC-12), which has immunomodulatory and antioxidant effects, on liver gene expression and aging phenomena in mice. Short-term EC-12 administration stimulated the expression of genes involved in lipid synthesis and metabolism in the liver. Furthermore, long-term EC-12 administration from 10 weeks to 1.5 years of age resulted in significant increases in blood interleukin (IL)-6 and IL-10 concentrations (both p < 0.05) and a significant decrease in the monocyte chemotactic protein-1 concentration (p < 0.05). These results indicated pathologic improvement, such as suppression of fat degeneration in the liver. These results suggest that continuous EC-12 intake from a young age can suppress liver function abnormalities, which is one of the aging phenomena in old age, and contribute to health in old age.

Urolithin A-mediated augmentation of intestinal barrier function through elevated secretory mucin synthesis.

Maintaining the mucus layer is crucial for the innate immune system. Urolithin A (Uro A) is a gut microbiota-derived metabolite; however, its effect on mucin production as a physical barrier remains unclear. This study aimed to elucidate the protective effects of Uro A on mucin production in the colon. In vivo experiments employing wild-type mice, NF-E2-related factor 2 (Nrf2)-deficient mice, and wild-type mice treated with an aryl hydrocarbon receptor (AhR) antagonist were conducted to investigate the physiological role of Uro A. Additionally, in vitro assays using mucin-producing cells (LS174T) were conducted to assess mucus production following Uro A treatment. We found that Uro A thickened murine colonic mucus via enhanced mucin 2 expression facilitated by Nrf2 and AhR signaling without altering tight junctions. Uro A reduced mucosal permeability in fluorescein isothiocyanate-dextran experiments and alleviated dextran sulfate sodium-induced colitis. Uro A treatment increased short-chain fatty acid-producing bacteria and propionic acid concentration. LS174T cell studies confirmed that Uro A promotes mucus production through the AhR and Nrf2 pathways. In conclusion, the enhanced intestinal mucus secretion induced by Uro A is mediated through the actions of Nrf-2 and AhR, which help maintain intestinal barrier function.

Investigation of activation-induced markers (AIM) in porcine T cells by flow cytometry.

Activation-induced markers (AIMs) are frequently analyzed to identify re-activated human memory T cells. However, in pigs the analysis of AIMs is still not very common. Based on available antibodies, we designed a multi-color flow cytometry panel comprising pig-specific or cross-reactive antibodies against CD25, CD69, CD40L (CD154), and ICOS (CD278) combined with lineage/surface markers against CD3, CD4, and CD8α. In addition, we included an antibody against tumor necrosis factor alpha (TNF-α), to study the correlation of AIM expression with the production of this abundant T cell cytokine. The panel was tested on peripheral blood mononuclear cells (PBMCs) stimulated with phorbol 12-myristate 13-acetate (PMA)/ionomycin, Staphylococcus enterotoxin B (SEB) or PBMCs from African swine fever virus (ASFV) convalescent pigs, restimulated with homologous virus. PMA/ionomycin resulted in a massive increase of CD25/CD69 co-expressing T cells of which only a subset produced TNF-α, whereas CD40L expression was largely associated with TNF-α production. SEB stimulation triggered substantially less AIM expression than PMA/ionomycin but also here CD25/CD69 expressing T cells were identified which did not produce TNF-α. In addition, CD40L-single positive and CD25+CD69+CD40L+TNF-α- T cells were identified. In ASFV restimulated T cells TNF-α production was associated with a substantial proportion of AIM expressing T cells but also here ASFV-reactive CD25+CD69+TNF-α- T cells were identified. Within CD8α+ CD4 T cells, several CD25/CD40L/CD69/ICOS defined phenotypes expanded significantly after ASFV restimulation. Hence, the combination of AIMs tested will allow the identification of primed T cells beyond the commonly used cytokine panels, improving capabilities to identify the full breadth of antigen-specific T cells in pigs.

Delayed diagnosis in a child with strangulated mesenteric hernia.

Background: Strangulated intestinal obstruction is a life-threatening condition that should be considered as a differential diagnosis in children with shock. However, it has pitfalls in diagnosis and can lead to diagnostic errors. Case Presentation: A 3-month-old male patient presented with a pale complexion lasting 2 h and abnormal crying. He was in shock with lactic acidosis, altered mental status, and slight abdominal distension. He required volume resuscitation, vasoactive agents, and transfusion. On Day 2, he had marked abdominal distension and acute kidney injury, which required continuous kidney replacement therapy. Contrast-enhanced computed tomography revealed extensive intestinal ischemia. It took 33.5 h from his arrival to the computed tomography, leading to operative management. The small intestine had entered a mesenteric hiatus, leading to ischemia. He was diagnosed with strangulated mesenteric hernia. Conclusion: In this case, four pitfalls led to delayed diagnosis. Factors for diagnostic errors specific to strangulated intestinal obstruction and intensive care should be noted.

Persistence of the Antibacterial and Antiviral Effects after Skin Cleansing ~A New Approach to Suppress the Contact Infection~.

Handwashing represents an important personal hygiene measure for preventing infection. Herein, we report the persistence of antibacterial and antiviral effects after handwashing with fatty acid salt-based hand soap. To this end, we developed a new in vitro test method to measure persistence, utilizing coacervation formed by anionic surfactants and cationic polymers to retain highly effective soap components against each bacterium and virus on the skin. Coacervation with fatty acid salts and poly diallyldimethylammonium chloride (PDADMAC) as a cationic polymer allowed the persistence of antibacterial and antiviral effects against E. coli, S. aureus, and influenza virus even 4 h after handwashing. Furthermore, we confirmed an increase in the number of residual components effective against each bacterium and virus on the skin. In summary, the current findings describe an effective approach for enhancing the protective effects of handwashing.

On the Moisture Absorption Capability of Ionic Liquids.

Due to their many attractive physicochemical properties, ionic liquids (ILs) have received extensive attention with numerous applications proposed in various fields of science and technology. Despite this, the molecular origins of many of their properties, such as the moisture absorption capability, are still not well understood. For insight into this, we systematically synthesized 24 types of ILs by the combination of the dimethyl phosphate anion with various types of alkyl group-substituted cyclic cations─imidazolium, pyrazolium, 1,2,3-triazolium, and 1,2,4-triazolium cations─and performed a detailed analysis of the dehumidification properties of these ILs and their aqueous solutions. It was found that these IL systems have a high dehumidification capability (DC). Among the monocationic ILs, the best performance was obtained with 1-cyclohexylmethyl-4-methyl-1,2,4-triazolium dimethyl phosphate, whose DC (per mol) value is 14 times higher than that of popular solid desiccants like CaCl2 and silica gel. Dicationic ILs, such as 1,1'-(propane-1,3-diyl)bis(4-methyl-1,2,4-triazolium) bis(dimethyl phosphate), showed an even better moisture absorption, with a DC (per mol) value about 20 times higher than that of CaCl2. Small- and wide-angle X-ray scattering measurements of eight types of 1,2,4-triazolium dimethyl phosphate ILs were performed and revealed that the majority of these ILs form nanostructures. Such nanostructures, which vary with the identity of the IL and the water content, fall into three main categories: bicontinuous microemulsions, hexagonal cylinders, and micelle-like structures. Water in the solutions exists primarily in polar regions in the nanostructures; these spaces function as water pockets at relatively low water concentrations. Since the structure and stability of the aggregated forms of the ILs are mainly governed by the interactions of nonpolar groups, the alkyl side chains of the cations play an important role in the DC and temperature-dependent equilibrium water vapor pressure of the IL solutions. Our experimental findings and molecular dynamics simulation results shed light on the moisture absorption mechanism of the IL aqueous solutions from a molecular perspective.

Relationship between the components of mare breast milk and foal gut microbiome: shaping gut microbiome development after birth.

The gut microbiota (GM) is essential for mammalian health. Although the association between infant GM and breast milk (BM) composition has been well established in humans, such a relationship has not been investigated in horses. Hence, this study was conducted to analyze the GM formation of foals during lactation and determine the presence of low-molecular-weight metabolites in mares' BM and their role in shaping foals' GM. The fecal and BM samples from six pairs of foals and mares were subjected to 16S ribosomal RNA metagenomic and metabolomic analyses, respectively. The composition of foal GM changed during lactation time; hierarchical cluster analysis divided the fetal GM into three groups corresponding to different time points in foal development. The level of most metabolites in milk decreased over time with increasing milk yield, while threonic acid and ascorbic acid increased. Further analyses revealed gut bacteria that correlated with changes in milk metabolites; for instance, there was a positive correlation between Bacteroidaceae in the foal's gut microbiota and serine/glycine in the mother's milk. These findings help improve the rearing environment of lactating horses and establish artificial feeding methods for foals.

Hydrogen peroxide in breast milk is crucial for gut microbiota formation and myelin development in neonatal mice.

Early life environment influences mammalian brain development, a growing area of research within the Developmental Origins of Health and Disease framework, necessitating a deeper understanding of early life factors on children's brain development. This study introduces a mouse model, LAO1 knockout mice, to investigate the relationship between breast milk, the gut microbiome, and brain development. The results reveal that breast milk's reactive oxygen species (ROS) are vital in shaping the neonatal gut microbiota. Decreased hydrogen peroxide (H2O2) levels in milk disrupt the gut microbiome and lead to abnormal metabolite production, including D-glucaric acid. This metabolite inhibits hippocampal myelin formation during infancy, potentially contributing to behavioral abnormalities observed in adulthood. These findings suggest that H2O2 in breast milk is crucial for normal gut microbiota formation and brain development, with implications for understanding and potentially treating neurodevelopmental disorders in humans.

Perturbed maternal microbiota shapes offspring microbiota during early colonization period in mice.

Recent studies have highlighted the impact of disrupted maternal gut microbiota on the colonization of offspring gut microbiota, with implications for offspring developmental trajectories. The extent to which offspring inherit the characteristics of altered maternal gut microbiota remains elusive. In this study, we employed a mouse model where maternal gut microbiota disruption was induced using non-absorbable antibiotics. Systematic chronological analyses of dam fecal samples, offspring luminal content, and offspring gut tissue samples revealed a notable congruence between offspring gut microbiota profiles and those of the perturbed maternal gut microbiota, highlighting the profound influence of maternal microbiota on early-life colonization of offspring gut microbiota. Nonetheless, certain dominant bacterial genera in maternal microbiota did not transfer to the offspring, indicating a bacterial taxonomy-dependent mechanism in the inheritance of maternal gut microbiota. Our results embody the vertical transmission dynamics of disrupted maternal gut microbiota in an animal model, where the gut microbiota of an offspring closely mirrors the gut microbiota of its mother.

The quality of life and work productivity are affected by the presence of nausea/vomiting in patients taking iron preparations for heavy menstrual bleeding or anemia: a population-based cross-sectional survey in Japan.

BACKGROUND: Patients with iron deficiency anemia are treated with iron preparations, but gastrointestinal symptoms such as nausea and vomiting occur frequently. These symptoms may negatively affect the quality of life and work productivity in patients with iron deficiency anemia. This study assessed the impact of nausea and vomiting on the quality of life and work productivity of patients taking iron preparations for heavy menstrual bleeding or anemia. METHODS: An online survey was conducted among patients taking iron preparations for heavy menstrual bleeding or anemia. Demographic data and information about medication use and the health condition were collected. The patients were asked to answer the 5-level EQ-5D version, and work productivity and activity impairment questionnaires. The outcomes were reported by patients in the presences of nausea, vomiting, and nausea or vomiting. The association with the 5-level EQ-5D version utility score for the severity and frequency of the symptoms were also assessed. RESULTS: A total of 385 patients were enrolled, and 96 were patients with nausea or vomiting, of which 94 were with nausea and 27 were with vomiting. The 5-level EQ-5D version utility scores for the patients with nausea, vomiting, and nausea or vomiting were significantly lower than those of the patients without these symptoms (p < 0.001 for each). The 5-level EQ-5D version utility score was correlated with the severity of nausea and the frequency of vomiting per day (p < 0.001 for each). As for the work productivity and activity impairment, the presenteeism, the overall work impairment, and the activity impairment of the patients with nausea, vomiting, and nausea or vomiting were significantly higher than those without these symptoms (p < 0.001 for each). The absenteeism was slightly higher trend was observed, but not significant. CONCLUSION: Patients taking iron preparations who have nausea or vomiting experience a significant burden in terms of poorer quality of life and higher work productivity impairment. TRIAL REGISTRATION: UMIN000045700 ( http://www.umin.ac.jp/ctr/ ). Registered on October 11, 2021.

Dietary Supplementation of Vitamin B12 to Rats Fed High-Amylose Cornstarch Normalizes Propionate Fermentation in the Colon.

Since propionate exerts several physiological effects, maintenance of its normal colonic fermentation is essential. To investigate whether vitamin B12 (VB12) is essential for normal propionate fermentation by colonic bacteria, via the succinate pathway, we examined if high-amylose cornstarch (HACS) feeding activated such a pathway, if high HACS feeding impaired propionate fermentation, and if oral VB12 supplementation normalized propionate fermentation. Male rats were given control, 20% HACS or 3% fucose diets (Expt. 1); a VB12-free control diet or one supplemented with 5-30% HACS (Expt. 2); and the 20% HACS diet supplemented with 0.025-25 mg/kg of VB12 (Expt. 3), for 14 d. HACS feeding significantly increased cecal succinate concentration, activating the succinate pathway (Expt. 1). Cecal cobalamin concentration in 20% and 30% HACS groups was about 75% of that in the control group (Expt. 2). Cecal succinate and propionate concentrations significantly increased and decreased in 30% HACS groups, respectively, compared with the control group. Although HACS group supplemented with 0.025 mg/kg of VB12 had a low concentration of cecal propionate, adding high amounts of VB12 to HACS diets provided sufficient amounts of VB12 to rat ceca and increased cecal propionate concentration (Expt. 3). Compared with the non-HACS group, the relative abundance of Akkermansia muciniphila, but not Bacteroides/Phocaeicola, was lower in the HACS counterpart and showed improvement with increased VB12 doses. To summarize, feeding high HACS decreased and increased cecal VB12 and succinate concentrations, respectively. Furthermore, colonic delivery of sufficient amounts of VB12 to rats likely reduced accumulation of succinate and normalized propionate fermentation.

Accurate estimation of modulation amplitude in Brillouin optical correlation-domain reflectometry based on Rayleigh noise spectrum.

In Brillouin optical correlation-domain reflectometry (BOCDR), spatial resolution relies on the modulation amplitude of the light. We propose a Rayleigh-based method that utilizes the spectral width of Rayleigh-induced noise to measure this amplitude without altering the setup or requiring an optical spectrum analyzer. With high frequency resolution and ease of implementation, our approach enhances the convenience and accuracy of spatial resolution evaluation in BOCDR.

Alpha-glycosyl isoquercitrin alleviates subchronic social defeat stress-induced depression symptoms by modulating the microbiota-gut-brain axis in mice.

AIMS: Increasing evidence suggests a link between gut microbial dysbiosis and the pathogenesis of depression. Alpha-glycosyl isoquercitrin (AGIQ), consisting of isoquercitrin and its glycosylated quercetin, has beneficial effects on the gut microbiome and brain function. Here, we detected the potential antidepressant impact of a four-week administration of AGIQ and its underlying mechanisms using a mouse model of depression. MAIN METHODS: Male C57BL/6 mice were orally administered AGIQ (0.05 % or 0.5 % in drinking water) for 28 days; subchronic social defeat stress was performed in the last 10 days. Behavior tests were conducted to assess anxiety and depressive-like behaviors. Additionally, evaluations encompassed 5-hydroxytryptamine (5-HT) levels, the gut microbiota composition, lipopolysaccharide (LPS) concentrations, short-chain fatty acids levels, and intestinal barrier integrity changes. KEY FINDINGS: AGIQ significantly alleviated depression-like behaviors and increased hippocampal 5-HT levels. Further, AGIQ mitigated stress-induced gut microbial abnormalities and reduced the levels of LPS in the serum, which affected the relative gene expression levels of 5-HT biosynthesis enzymes in vitro. Furthermore, AGIQ reversed the reduced butyrate levels in cecal contents and improved the impaired intestinal barrier by increasing the expression of colonic zonula occluden-1 (ZO-1) and occludin, thereby decreasing LPS leakage. SIGNIFICANCE: Our results suggest that AGIQ could improve stress-induced depression by regulating the gut microbiome, which inhibits LPS production and maintains the gut barrier. This is the first report on the potential effect of AGIQ on depression via the gut microbiota-brain axis, shedding new light on treatment options.

Comparison of the fecal bacterial microbiota in mice, rats, and pigs after oral administration of alpha-glycosyl isoquercitrin.

Alpha-glycosyl isoquercitrin (AGIQ) is composed of isoquercitrin and its glucosylated derivatives and has many biological activities, including anti-inflammatory, antioxidant, and anti-cancer properties. However, the effect of AGIQ administered orally on gut microbiota composition remains unclear. The objective of this study was to evaluate the effect of AGIQ on the gut microbiota of animals in different dose groups. Male rats and mice received different doses of AGIQ (1.5%, 3%, or 5% w/v) in diet for carcinogenic or chronic toxicity studies (rasH2 mice: 6 months; Sprague-Dawley rats: 12 months). Male minipigs received 100, 300, or 1000 mg/kg/day for 28 days. Fecal samples were collected from the different animal species and analyzed using 16S-rRNA gene sequencing. No significant changes were observed in alpha and beta diversity of the gut microbiota. Characteristic bacteria that responded to AGIQ were identified in each animal species, and, interestingly, Kineothrix alysoides, a butyrate-producing bacterium, was commonly detected in all three species, suggesting that it may be related to the biological activities of AGIQ. AGIQ selectively modulated the number of beneficial butyrate-producing commensal bacterium beneficial bacteria without changing the diversity of gut microbiota, which further supports the safe use of AGIQ in food products.

Changes in fecal microbiota during estrous cycle in healthy thoroughbred mares.

Gut microbiota plays a crucial role in various physiological processes, including the regulation of the reproductive system and steroid sex hormones. Throughout the normal estrous cycle of healthy mares, the levels of estradiol-17ß (E2) and progesterone (P4) in the blood exhibit periodic changes. To investigate the relationship between cyclic changes in steroid sex hormones and the gut microbiome of mares, we analyzed the fecal microbiota composition in healthy mares during the typical estrous cycle. Blood and fecal samples from five healthy mares were collected, E2 and P4 levels in serum were analyzed using radioimmunoassay (RIA), and the gut microbiome was analyzed by 16S rRNA sequencing. The overall richness and composition of the gut microbiota remained relatively stable during the normal estrous cycle in mares. The Linear Discriminant Analysis Effect Size analysis of the microbial composition during the follicular and luteal phases identified the Rhodococcus genus as differentially abundant. These findings indicate that the mare's gut microbiota's significant composition remains consistent throughout the estrous cycle. At the same time, specific low-abundance pathogenic bacteria exhibit changes that align with sexual hormonal fluctuations.

D-alanine Inhibits Murine Intestinal Inflammation by Suppressing IL-12 and IL-23 Production in Macrophages.

BACKGROUND AND AIMS: Free D-amino acids, which have different functions from L-amino acids, have recently been discovered in various tissues. However, studies on the potential interactions between intestinal inflammation and D-amino acids are limited. We examined the inhibitory effects of D-alanine on the pathogenesis of intestinal inflammation. METHODS: We investigated serum D-amino acid levels in 40 patients with ulcerative colitis and 34 healthy volunteers. For 7 days [d], acute colitis was induced using dextran sulphate sodium in C57BL/6J mice. Plasma D-amino acid levels were quantified in mice with dextran sulphate sodium-induced colitis, and these animals were administered D-alanine via intraperitoneal injection. IFN-γ, IL-12p35, IL-17A, and IL-23p19 mRNA expression in the colonic mucosa was measured using real-time polymerase chain reaction [PCR]. In vitro proliferation assays were performed to assess naïve CD4+ T cell activation under Th-skewing conditions. Bone marrow cells were stimulated with mouse macrophage-colony stimulating factor to generate mouse bone marrow-derived macrophages. RESULTS: Serum D-alanine levels were significantly lower in patients with ulcerative colitis than in healthy volunteers. Dextran sulphate sodium-treated mice had significantly lower plasma D-alanine levels than control mice. D-alanine-treated mice had significantly lower disease activity index than control mice. IFN-γ, IL-12p35, IL-17A, and IL-23p19 mRNA expression levels were significantly lower in D-alanine-administered mice than in control mice. D-alanine suppressed naïve T cell differentiation into Th1 cells in vitro, and inhibited the production of IL-12p35 and IL-23p19 in bone marrow-derived macrophages. CONCLUSIONS: Our results suggest that D-alanine prevents dextran sulphate sodium-induced colitis in mice and suppresses IL-12p35 and IL-23p19 production in macrophages.

Oral Function and the Oral Microbiome in the Elderly in the Kyotango Area.

INTRODUCTION: Prevention of tooth loss contributes to an extended life expectancy, namely longevity. Aging-related oral hypofunction, including tooth loss, markedly increases the risks of functional disorder and mortality. Dysbiosis of the oral microbiome has recently been associated with various diseases, such as liver cirrhosis, pancreatic cancer, colorectal cancer, and inflammatory bowel disease. Therefore, the relationship between the oral microbiome and systemic health has been attracting increasing attention. In the present study, we examined oral function and the oral microbiome in the elderly in a world-leading longevity area. MATERIALS AND METHODS: An oral examination, chewing ability/tongue-lip motor function/saliva tests, and a metagenomic analysis with a 16S rRNA gene-targeting next-generation sequencer were conducted on 78 subjects aged ≥80 years. Twenty-six healthy individuals aged between 20 and 39 years were also investigated as controls. The data obtained were statistically analyzed. The protocol of the present study was approved by the Ethics Review Board of our university (ERB-C-885). RESULTS: Chewing ability, tongue-lip motor function, and saliva volume were normal in elderly subjects with a current tooth number ≥20, but were significantly lower in those with a current tooth number <20. The oral microbiome in elderly subjects with a current tooth number ≥20 and young controls differed from that in elderly subjects with a current tooth number <20. CONCLUSION: Tooth number ≥20 in elderly subjects in the longevity area contributed to the maintenance of both oral function and the diversity of the oral microbiome.

Synthesis and characterization of one-handed helical oligo(o-phenylene)s: control of axial chirality by planar chiral [2.2]paracyclophane.

Optically active oligo(o-phenylene)-layered molecules were synthesized from planar chiral enantiopure [2.2]paracyclophane. Their structures and optical properties were characterized by experimental and theoretical approaches. The axial chiralities between phenylene rings of the oligo(o-phenylene)s were controlled by the planar chirality to form one-handed helical structures. The o-quinquephenyl-layered molecule was emissive, and circularly polarized luminescence was observed with a high anisotropy factor (|glum| value) of 0.012.

Aggregation-induced emission from optically active X-shaped molecules based on planar chiral [2.2]paracyclophane.

An optically active π-stacked molecule was synthesized incorporating planar chiral [2.2]paracyclophane and o-carborane units to impart circularly polarized luminescence and aggregation-induced emission properties to the molecule. The molecule exhibited a strong emission from the aggregated state in a mixed solvent system (H2O/THF) and the solid state in the PMMA matrix. In the aggregated state, weak circularly polarized luminescence was observed owing to the random intermolecular orientation. On the other hand, the circularly polarized luminescence was clearly observed in the PMMA film containing 1 wt% molecule. Theoretical studies using time-dependent density functional theory reproduced the molecule's circular dichroism and circularly polarized luminescence properties.