Expression of SMADs in orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine model.

Activin A promotes the development of endometriotic lesions in a murine model of endometriosis, and the immunohistochemical localization of phosphorylated suppressor of mothers against decapentaplegic homolog 2/3 (pSMAD2/3) complex in endometriotic lesions has been reported. Activin may therefore be involved in the development and proliferation of endometriotic cells via the SMAD signaling pathway. However, few detailed reports exist on SMAD7 expression in endometriosis. The purpose of this study was to investigate the expression of pSMAD2/3 or pSMAD3 and SMAD7 in the orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine model and the effect of activin A on pSMAD2/3 and SMAD7 expression. We established an endometriosis murine model via the intraperitoneal administration of endometrial tissue and blood from donor mice. Activin A was intraperitoneally administered to the activin group. We immunohistochemically evaluated orthotopic endometria, ovarian endometriotic tissues, and endometriotic lesions in the murine model followed by western blotting. We found that pSMAD3 and SMAD7 were expressed in ovarian endometriosis and orthotopic endometria from patients with and without endometriosis. In the murine model, endometriotic lesions expressed pSMAD2/3 and SMAD7 in the activin and control groups, and higher SMAD7 expression was found in the activin group. To the best of our knowledge, this study is the first to show that SMAD7 expression is upregulated in endometriosis. In conclusion, these results suggest that activin A activates the SMAD signaling pathway and promotes the development of endometriotic lesions, thus identifying SMAD7 as a potential therapeutic target for endometriosis.

Developmental Changes in Hypothalamic and Serum Oxytocin Levels in Prenatally Normally Nourished and Undernourished Rats.

Changes in the activities of some metabolic factors have been suggested to increase the risk of conditions associated with the Developmental Origins of Health and Disease (DOHaD). We examined changes in oxytocin (OT), a metabolic factor, and OT receptor (OTR) mRNA levels throughout the developmental period in rats of intrauterine undernutrition. Pregnant rats were divided into two groups: a maternal normal nutrition (mNN) and maternal undernutrition (mUN) group. Serum OT concentrations and hypothalamic mRNA levels of OT and OTR were measured in both offspring at various postnatal stages. Both offspring showed significant increases in serum OT concentrations during the neonatal period, significant reductions around the pubertal period, and significant increases in adulthood. Hypothalamic OT mRNA expression levels gradually increased from the neonatal to pubertal period and decreased in adulthood in both offspring. In the pre-weaning period, hypothalamic OT mRNA expression levels were significantly lower in the mUN offspring than in the mNN offspring. In the mUN offspring, hypothalamic OTR mRNA expression levels transiently increased during the neonatal period, decreased around the pubertal period, and increased again in adulthood, whereas transient changes were not detected in mNN offspring. These changes could affect nutritional and metabolic regulation systems in later life and play a role in the mechanisms underlying DOHaD.

The effects of androgens on metabolic functions in females.

The metabolic effects of androgens and their underlying mechanisms in females have been revealed by recent studies. An excess of androgens can have adverse effects on feeding behavior and metabolic functions and induce metabolic disorders / diseases, such as obesity, insulin resistance, and diabetes, in women and experimental animals of reproductive age. Interestingly, these effects of androgens are not observed in ovariectomized animals, indicating that their effects might be dependent on the estrogen milieu. Central and peripheral mechanisms, such as alterations in the activity of hypothalamic factors, reductions in energy expenditure, skeletal muscle insulin resistance, and ß-cell dysfunction, might be related to these androgens' effects. J. Med. Invest. 68 : 228-231, August, 2021.

Detection and isolation of low molecular weight alginate- and laminaran-susceptible gut indigenous bacteria from ICR mice.

Alginate and laminaran are the main water-soluble polysaccharides in edible brown algae such as arame Eisenia bicyclis. To determine the alginate- and/or laminaran-susceptible indigenous bacteria (SIB) in the gut, the caecal microbiomes of ICR mice fed a diet containing 2% low molecular weight (LMW ≒50 kDa) alginate or laminaran were analysed by 16S rRNA gene (V4) amplicon sequencing. At the phylum level abundances, compared to those in mice fed a no-fibre diet, Firmicutes was lower and Bacteroidetes was higher in both LMW alginate- or laminaran-fed mouse groups. At the operational taxonomic unit level, Bacteroides acidifaciens- and Bacteroides intestinalis-like bacteria were considered alginate- and laminaran-SIB, respectively. B. acidifaciens PS-4 isolated from the ICR mice fermented LMW alginate and laminaran and mainly produced succinate. B. intestinalis ALB-11 also isolated from these mice fermented laminaran and mainly produced lactate. These SIB might exert interactive effects with edible brown algal consumption and affect host health.

In vitro antioxidant, anti-glycation and immunomodulation activities of fermented blue-green algae Aphanizomenon flos-aquae.

To clarify the antioxidant, anti-glycation and immunomodulatory capacities of fermented blue-green algae Aphanizomenon flos-aquae (AFA), hot aqueous extract suspensions made from 10% AFA were fermented by Lactobacillus plantarum AN7 and Lactococcus lactis subsp. lactis Kushiro-L2 strains isolated from a coastal region of Japan. The DPPH and O2- radical scavenging capacities and Fe-reducing power were increased in the fermented AFA. The increased DPPH radical scavenging capacity of the fermented AFA was fractionated to mainly < 3 kDa and 30-100 kDa. The increased O2- radical scavenging capacities were fractionated to mainly < 3 kDa. Anti-glycation activity in BSA-fructose model rather than BSA-methylglyoxal model was increased by the fermentation. The increased anti-glycation activity was fractionated to mainly 30-100 kDa. The NO concentration in the murine macrophage RAW264.7 culture media was high with the fermented AFA. The increased immunomodulation capacity was also fractionated to mainly 30-100 kDa. These results suggest that the fermented AFA is a more useful material for health foods and supplements.

Empirical research on the utility of a preparation manual for a disaster medical response drill.

PURPOSE: It is difficult for emergency physicians to plan and execute a disaster medical response drill while conducting their daily work activities. Readily available drill preparation manuals are therefore essential, alongside assessment methods to ensure quality. Here, we propose email text analysis as a manual assessment method, and investigate its validity. METHODS: The preparation status of two similar large-scale disaster medical response drills were compared. All email texts exchanged during the preparation stage were analyzed, and frequently appearing words (quality element) and word counts (quantity element) were compared between Drill 1, which was organized without a manual, and Drill 2, organized with a manual. RESULTS: Word frequency analysis revealed that the key components of the manual (visualization of necessary work, preparation of documents in a certain format, and clarification of aims of the drill) contributed to the effectiveness of the preparation process for Drill 2. Furthermore, work volume during the preparation for Drill 2 was decreased by 41.9% from that during the preparation for Drill 1. CONCLUSION: Preparation of a high-quality manual is crucial so that emergency physicians can plan and execute a disaster medical response drill. Email text analysis can serve as an objective method assessing the quality of manuals.