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.

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.

Synthesis of Two Novel Optically Active #-Shaped Cyclic Tetramers Based on Planar Chiral [2.2]Paracyclophanes.

This study reports the synthesis of optically active cyclic tetramers comprising four stacked π-electron systems from two enantiomerically pure [2.2]paracyclophane compounds (bis-(para)-pseudo-ortho- and bis-(para)-pseudo-meta-tetrasubstituted [2.2]paracyclophane compounds). Depending on the combination of the absolute configurations of the planar chiral pseudo-ortho- and pseudo-meta-[2.2]paracyclophane units, the cyclic tetramers formed either parallel-#- or weave-#-structures. The optical and chiroptical properties of both structures were investigated experimentally and theoretically. In particular, the weave-#-shaped cyclic tetramer exhibited good chiroptical properties and emitted circularly polarized luminescence (CPL) with a high anisotropy factor (|glum | value of the order of 10-3 ) and a CPL brightness (BCPL ) higher than 100.

Direct Synthesis of ABCD-Porphyrin Platinum(II) Complexes via Dehydrative Aromatization.

Since the development of the first method for porphyrin synthesis by Rothemund in 1935, porphyrin derivatives have been widely investigated and have played an essential role in chemical sciences. Most synthetic routes of porphyrins involve oxidative aromatization. Herein, we present a synthetic method to produce ABCD-porphyrins, including chiral ones, through a one-pot reaction involving "coordination, cyclization, and dehydrative aromatization" using a mono-dipyrrinatoPt(II)Cl(COE) (COE=cyclooctene) complex as a platinum template.

Development of a panel for detection of pathogens in xenotransplantation donor pigs.

There have been high expectations in recent years of using xenotransplantation and regenerative medicine to treat humans, and pigs have been utilized as the donor model. Pigs used for these clinical applications must be microbiologically safe, that is, free of infectious pathogens, to prevent infections not only in livestock, but also in humans. Currently, however, the full spectrum of pathogens that can infect to the human host or cause disease in transplanted porcine organs/cells has not been fully defined. In the present study, we thus aimed to develop a larger panel for the detection of pathogens that could potentially infect xenotransplantation donor pigs. Our newly developed panel, which consisted of 76 highly sensitive PCR detection assays, was able to detect 41 viruses, 1 protozoa, and a broad range of bacteria (by use of universal 16S rRNA primers). The applicability of this panel was validated using blood samples from uterectomy-born piglets, and pathogens suspected to be vertically transmitted from sows to piglets were successfully detected. We estimate that, at least for viruses and bacteria, the number of target pathogens detected by the developed screening panel should suffice to meet the microbiological safety levels required worldwide for xenotransplantation and/or regenerative therapy. This panel provides greater diagnosis options to produce donor pigs so that it would render unnecessary to screen for all pathogens listed. Instead, the new panel could be utilized to detect only required pathogens within a given geographic range where the donor pigs for xenotransplantation have been and/or are being developed.

Characteristics of Gastric Mucosa-Associated Microbiota in Patients with Early Gastric Cancer After Successful Helicobacter pylori Eradication.

BACKGROUND: Helicobacter pylori (H. pylori) is widely recognized as a definite carcinogen in gastric cancer (GC). Although H. pylori eradication reduces the risk of GC, GC recurrence has been detected even after successful H. pylori eradication. Recently, the analysis of gut microbiota was reported. AIMS: This study aimed to evaluate the correlation between gastric mucosa-associated microbiota (G-MAM) and early gastric cancer (EGC) after successful H. pylori eradication. METHODS: In this pilot study, G-MAM were collected during the esophagogastroduodenoscopy of 17 patients, receiving H. pylori eradication therapy at least 5 years ago. The patients were divided into those with EGC (the EGC group, 8 patients) and those without EGC (the NGC group, 9 patients). Microbial samples in the greater curvature of the pyloric site were obtained using an endoscopic cytology brush, and the G-MAM profiles of each sample were analyzed using 16S rRNA V3-V4 gene sequencing. RESULTS: Between the two groups, there was no significant difference in the median age, sex, median period after successful eradication of H. pylori, the α diversity, and the average abundance at the phylum level. At the genus level, the average abundance of Unclassified Oxalobacteraceae, Capnocytophaga, and Haemophilus was significantly lower in the EGC group than in the NGC group (0.89 vs. 0.14%, P < 0.01, 0.28 vs. 0.00%, P < 0.01 and 5.84 vs. 2.16%, P = 0.034, respectively). CONCLUSIONS: We demonstrated alternations in the profiles of G-MAM between the two groups. Our results suggest that G-MAM may influence carcinogenesis after successful H. pylori eradication.

2'-Fucosyllactose Alleviates Early Weaning-Induced Anxiety-Like Behavior, Amygdala Hyperactivity, and Gut Microbiota Changes.

Early life stress has a significant impact on development of the central nervous system (CNS), with lasting rather than transient consequences; therefore, it is important to alleviate these effects. In recent years, functional communication between the CNS and gut microbiota through the so-called brain-gut-microbiota axis has been examined, and it is likely that prebiotics contribute to development of the CNS through the gut microbiota. In this study, we performed behavioral, neurohistological, and fecal microbiota analyses in early-weaned mice to examine the effects of 2'-fucosyllactose (2'-FL), a human milk oligosaccharide, on anxiety induced by early life stress. Mice weaned at 17 d old (17-d mice) showed anxiety-like behaviors, such as decreased time in the open arms in the elevated plus maze test, compared to mice weaned at 24 d old (24-d mice). The number of cells that were positive for the neuronal activity marker c-Fos in the amygdala was also higher in 17-d mice. The behavioral and neural abnormalities caused by early weaning were alleviated by post-weaning ingestion of 2'-FL. The composition of the fecal microbiota differed among control diet-fed 24-d and 17-d mice, and 2'-FL diet-fed 17-d mice. These findings indicate that human milk oligosaccharides 2'-FL alleviate early stress-induced anxiety, amygdala hyperactivity, and gut microbiota changes.

Matcha green tea beverage moderates fatigue and supports resistance training-induced adaptation.

BACKGROUND: Resistance training adaptively increases muscle strength and mass, contributing to athletic performance and health promotion. Dietary intervention with natural foods provides nutrients that help accelerate muscle adaptation to training. Matcha green tea contains several bioactive factors such as antioxidants, amino acids, and dietary fibers; however, its effect on muscle adaptation is unclear. In this study, we aimed to investigate the effects of matcha beverage intake on muscle adaptation to resistance training. METHODS: Healthy, untrained men were randomized into placebo and matcha groups. Participants consumed either a matcha beverage containing 1.5 g of matcha green tea powder or a placebo beverage twice a day and engaged in resistance training programs for 8 (trial 1) or 12 weeks (trial 2). RESULTS: In trial 1, maximum leg strength after training tended to increase more in the matcha group than that in the placebo group. In the matcha group, subjective fatigue after exercise at 1 week of training was lower than that in the placebo group. Gut microbe analysis showed that the abundance of five genera changed after matcha intake. The change in Ruminococcus, Butyricimonas, and Oscillospira compositions positively correlated with the change in maximum strength. In trial 2, the change in skeletal muscle mass in response to training was larger in the matcha group. In addition, the salivary cortisol level was lower in the matcha group than that in the placebo group. CONCLUSION: Daily intake of matcha green tea beverages may help in muscle adaptation to training, with modulations in stress and fatigue responses and microbiota composition.

Impact of nausea/vomiting on EQ-5D-5L utility scores in patients taking iron preparations for heavy menstrual bleeding or anemia.

BACKGROUND: The purpose of this study was to establish an estimating equation to predict the 5-level EQ-5D version (EQ-5D-5L) utility score in patients taking iron preparations for heavy menstrual bleeding (HMB) or anemia and to evaluate whether the presence of nausea or vomiting was a significant predictor of EQ-5D-5L-based quality of life. METHODS: A cross-sectional survey was conducted to collect EQ-5D-5L utility scores and other patient reported outcomes from 385 patients taking iron preparations for HMB or anemia who were selected from the disease patient panel. Using the utility scores as objective variables, explanatory variable candidates were selected considering correlations, multicollinearity, and clinical validity. Predicting models were constructed using regression-based models (linear model, generalized linear model (GLM), Tobit model). Stepwise regression method was applied for selecting statistically significant (p < 0.05) predictors. Goodness-of-fit of models were assessed by mean absolute error and mean squared error (MSE). RESULTS: The EQ-5D-5L utility scores (mean ± standard deviation) of 96 patients with nausea/vomiting and 289 patients without nausea/vomiting were 0.67 ± 0.16 and 0.84 ± 0.14, respectively (p < 0.001). The presence of nausea/vomiting was shown to be the most significant factor reducing the utility score in the statistical models using the explanatory variable candidates selected in the study. As the results of the goodness-of-fit test, GLM with the smallest MSE was selected to establish the estimating equation. CONCLUSION: The estimating equation to predict the EQ-5D-5L utility scores in patients taking iron preparations for HMB or anemia was established. The presence of nausea/vomiting was found to be a factor significantly reducing utility scores, with a decrement of the value estimated to be -0.117. TRIAL REGISTRATION: UMIN000045700 ( http://www.umin.ac.jp/ctr/ ). Registered on October 11, 2021.

Astaxanthin attenuated the stress-induced intestinal motility disorder via altering the gut microbiota.

Gut microbiota and short-chain fatty acids (SCFAs) are recognized as key factors in the pathophysiology of irritable bowel syndrome. Astaxanthin is a carotenoid with strong antioxidant and anti-inflammatory activities. In this study, we examined the effects of astaxanthin on gut microbiota-, SCFAs-, and corticotropin-releasing factor (CRH)-induced intestinal hypermotility. Male Wistar rats (n=12 per group) were fed a diet with or without 0. 02% (w/w) astaxanthin for four weeks and CRH or saline was administered intravenously. The number of fecal pellets was counted 2 h after injection. Then the rats were sacrificed, and the cecal content were collected 3 h after injection. The number of feces was significantly increased by CRH injection in the control group (2.0 vs. 6.5; p=0.028), but not in the astaxanthin group (1.0 vs. 2.2; p=0.229) (n=6 per group). The cecal microbiota in the astaxanthin group was significantly altered compared with that in the control group. The concentrations of acetic acid (81.1 µmol/g vs. 103.9 µmol/g; p=0.015) and butyric acid (13.4 µmol/g vs. 39.2 µmol/g; p<0.001) in the astaxanthin group were significantly lower than that in the control group (n=12 per group). Astaxanthin attenuates CRH-induced intestinal hypermotility and alters the composition of gut microbiota and SCFAs.

Amelioration of Pulmonary Fibrosis by Matrix Metalloproteinase-2 Overexpression.

Idiopathic pulmonary fibrosis is a progressive and fatal disease with a poor prognosis. Matrix metalloproteinase-2 is involved in the pathogenesis of organ fibrosis. The role of matrix metalloproteinase-2 in lung fibrosis is unclear. This study evaluated whether overexpression of matrix metalloproteinase-2 affects the development of pulmonary fibrosis. Lung fibrosis was induced by bleomycin in wild-type mice and transgenic mice overexpressing human matrix metalloproteinase-2. Mice expressing human matrix metalloproteinase-2 showed significantly decreased infiltration of inflammatory cells and inflammatory and fibrotic cytokines in the lungs compared to wild-type mice after induction of lung injury and fibrosis with bleomycin. The computed tomography score, Ashcroft score of fibrosis, and lung collagen deposition were significantly reduced in human matrix metalloproteinase transgenic mice compared to wild-type mice. The expression of anti-apoptotic genes was significantly increased, while caspase-3 activity was significantly reduced in the lungs of matrix metalloproteinase-2 transgenic mice compared to wild-type mice. Active matrix metalloproteinase-2 significantly decreased bleomycin-induced apoptosis in alveolar epithelial cells. Matrix metalloproteinase-2 appears to protect against pulmonary fibrosis by inhibiting apoptosis of lung epithelial cells.

A randomized, double-blinded study evaluating effect of matcha green tea on human fecal microbiota.

Matcha green tea is made from powdered green tea leaves. Unlike regular green tea, Matcha green tea is believed to exert beneficial effects on the gut microbiota, as it is richer in nutrients such as tea catechins and insoluble dietary fiber. In the present study, we aimed to investigate the effects of consumption of Matcha green tea on the gut microbiota. Human participants were randomly assigned to a placebo (n = 16) or a Matcha green tea (n = 17) drink group and asked to drink the treatments for two weeks. Feces were collected from the participants pre- and post-treatment and fecal microbiota composition was analyzed by 16S rRNA metagenomic sequencing. The beta-diversity of microbial composition significantly (p<0.05) changed in MGT group but not in placebo group. In addition, the number of unique bacterial genera significantly (p<0.05) changed in the Matcha green tea group was 30, while it was only 3 in the Placebo group. Increase and decrease in abundances of Coprococcus and Fusobacterium, respectively, in the gut microbiota of Matcha green tea group, conferred potential health benefits to the host. The present study was registered in the UMIN Clinical Trial Registry (UMIN000043857).

Reduced abundance of butyric acid-producing bacteria in the ileal mucosa-associated microbiota of ulcerative colitis patients.

Compositional changes in the microbiota are associated with various inflammatory diseases, including ulcerative colitis (UC). Aim: This study aimed to investigate the mucosa-associated microbiota (MAM) in patients with UC and its difference related with disease activity and classification. Brush samples were collected from the terminal ileum and sigmoid colon during endoscopic procedures. The microbiota of samples was profiled using the Illumina MiSeq platform. The V3-V4 regions of the gene encoding 16S rRNA (460 bp) were amplified using PCR. Fifty UC patients and twenty healthy controls were enrolled. UC patients displayed significantly reduced α-diversity in both the ileum and sigmoid colon compared to controls. A difference in ß-diversity in the unweighted analysis was observed between the two groups. The abundance of Lactobacillus and Veillonella was significantly higher and that of Butyricicoccus, Ruminococcus and Lachnospiraceae was significantly lower in the ileum of UC patients than in controls. The abundance of Odoribacter in the ileum was significantly lower in left-sided colitis and pancolitis patients than in proctitis patients and lower in patients with highly severe disease activity than with mild disease activity. The reduction in abundance of butyric acid-producing bacteria, especially Odoribacter, in ileal MAM may play an important role in the pathophysiology of UC.

Partially hydrolyzed guar gum is associated with improvement in gut health, sleep, and motivation among healthy subjects.

Partially hydrolyzed guar gum dietary fiber is well recognized for a number of health benefits. In the present study, we aim to investigate the effects of partially hydrolyzed guar gum on constipation, intestinal microbiota as well as mental health in healthy subjects. In the randomized, parallel, double-blind, and placebo-controlled study the enrolled healthy men and women volunteers took either 3 g/day (T3) or 5 g/day (T5) of dietary fiber intakes for eight consecutive weeks compared to placebo (T0). The fecal characteristics, fecal microbiota, defecation characteristics, and quality of life (QOL) questionnaire were investigated. The results revealed a significant suppression in fecal potent harmful mucolytic bacteria in the T3 and T5 groups compared to the T0 group. The defecation frequency, excretory feeling, and scores of sleep and motivation questionnaire were also improved in the dietary fiber intake groups, showing a significant difference in the T5 group compared to the T0 group. In summary, the consumption of partially hydrolyzed guar gum dietary fiber is found effective in suppressing the potent harmful mucolytic bacteria that could be associated with the improvement of constipation-related symptoms including mental health in terms of sleep and motivation among the healthy subjects.

Water-soluble dietary fiber alleviates cancer-induced muscle wasting through changes in gut microenvironment in mice.

Cancer cachexia and the associated skeletal muscle wasting are considered poor prognostic factors, although effective treatment has not yet been established. Recent studies have indicated that the pathogenesis of skeletal muscle loss may involve dysbiosis of the gut microbiota and the accompanying chronic inflammation or altered metabolism. In this study, we evaluated the possible effects of modifying the gut microenvironment with partially hydrolyzed guar gum (PHGG), a soluble dietary fiber, on cancer-related muscle wasting and its mechanism using a colon-26 murine cachexia model. Compared with a fiber-free (FF) diet, PHGG contained fiber-rich (FR) diet-attenuated skeletal muscle loss in cachectic mice by suppressing the elevation of the major muscle-specific ubiquitin ligases Atrogin-1 and MuRF1, as well as the autophagy markers LC3 and Bnip3. Although tight-junction markers were partially reduced in both FR and FF diet-fed cachectic mice, the abundance of Bifidobacterium, Akkermansia, and unclassified S24-7 family increased by FR diet, contributing to the retention of the colonic mucus layer. The reinforcement of the gut barrier function resulted in the controlled entry of pathogens into the host system and reduced circulating levels of lipopolysaccharide-binding protein (LBP) and IL-6, which in turn led to the suppression of proteolysis by downregulating the ubiquitin-proteasome system and autophagy pathway. These results suggest that dietary fiber may have the potential to alleviate skeletal muscle loss in cancer cachexia, providing new insights for developing effective strategies in the future.

The Regional Specificity of Mucosa-Associated Microbiota in Patients with Distal Colorectal Cancer.

BACKGROUND/AIMS: Recent studies have demonstrated that the populations of several microbes are significantly increased in fecal samples from patients with colorectal cancer (CRC), suggesting their involvement in the development of CRC. The aim of this study was to identify microbes which are increased in distal CRCs and to identify the specific location of microbes increased in mucosal tissue around the tumor. METHODS: Tissue specimens were collected from surgical resections of 28 distal CRCs. Five samples were collected from each specimen (location A: tumor, B: adjacent normal mucosa, C: normal mucosa 1 cm proximal to the tumor, D: normal mucosa 3 cm proximally, and E: normal mucosa 6 cm proximally). The microbiota in the sample were analyzed using 16S rRNA gene amplicon sequencing and the relative abundance (RA) of microbiota compared among the 5 locations. RESULTS: At the genus level, the RA of Fusobacterium and Streptococcus at location A was the highest among the 5 locations, significantly different from that in location E. The dominant species of each genus was Fusobacterium nucleatum and Streptococcus anginosus. The RAs of these species gradually decreased from locations B to E with a statistically significant difference in F. nucleatum. The genus Peptostreptococcus also showed a similar trend, and the RA of Peptostreptococcus stomatis in location A was significantly associated with depth of tumor invasion and tumor size. CONCLUSION: Although the clinical relevance is not clear yet, these results suggest that F. nucleatum, S. anginosus, and P. stomatis can spread to the adjacent normal tissues and may change the surrounding microenvironment to support the progression of CRC.

Extending the Limbus-to-Cannula Distance to 6.0 mm During Pars Plana Vitrectomy in Highly Myopic Eyes.

PURPOSE: To evaluate the utility of extending the limbus-to-cannula distance to 6.0 mm during pars plana vitrectomy for highly myopic eyes. METHODS: Four eyes with axial lengths exceeding 31.0 mm, that underwent 25-gauge pars plana vitrectomy were retrospectively evaluated. Assuming that cannulas were inserted 3.5 mm and 6.0 mm from the corneal limbus, the distance from the cannula to the fovea (CF distance) was preoperatively evaluated using anterior segmental optical coherence tomography. Surgical complications were also investigated. RESULTS: The CF distance was shortened by 1.22 ± 0.05 mm and 1.22 ± 0.09 mm on the temporal and nasal sides, respectively, by inserting the cannula at 3.5 mm to 6.0 mm from the corneal limbus. As per the preoperatively measured CF distance, one of the cannulas was inserted 6.0 mm from the corneal limbus in three eyes. Their cannulas were confirmed to be inserted at the pars plana, and no surgical complications associated with this technique were observed. CONCLUSION: Extending the limbus-to-cannula distance to 6.0 mm during pars plana vitrectomy could be one of the options to reach the posterior pole in highly myopic eyes. A preoperatively measured CF distance can be a clinical criterion in determining the cannula position.

Central fibrous area in the glomerular vascular pole consists of fibrous collagens and is associated with advanced age: a cross-sectional study.

BACKGROUND: For the optimal management of patients with both allograft kidneys and native kidney diseases, the recognition of the histological features associated with older age is important. This is because most pathological findings are non-specific. Central fibrous areas (CFAs) have recently been proposed to be age-related. However, the components of CFAs and whether CFAs are observed in various kidney diseases remain undetermined. This cross-sectional study was undertaken to clarify the histological features, epidemiology, and clinicopathological features of CFAs. METHODS: One hundred and one consecutive kidney needle biopsy specimens were retrospectively collected from seven facilities in the Hokuriku region and diagnosed at the Kanazawa University Hospital in 2015. First, the components of CFAs were analyzed using normal histostaining, immunostaining, and electron microscopy. Second, the patients were divided into two groups (CFA [+] or CFA [-]) according to the presence of CFA in the obtained samples. Clinical and histological features were compared between the two groups, and factors associated with CFA formation were determined using univariate and multivariate analyses. The number of CFAs per specimen was counted in the CFA (+) group. Third, the presence of myofibroblasts in CFA was examined by immunostaining. RESULTS: CFAs were observed in 56 of 101 patients (55.4%) with various kidney diseases. CFAs consist of fibrillar collagens (collagen I and III) in addition to non-fibrillar collagens (collagen IV and VI), as confirmed by electron microscopy. Clinically, the CFA (+) group was older and had a significantly higher prevalence of hypertension and hyperlipidemia than the CFA (-) group. Histologically, elastofibrosis of the interlobular artery, arteriolar hyalinosis, and membranous nephropathy were significantly more evident in the CFA (+) group than in the CFA (-) group. Multivariate analysis revealed that older age was the sole factor associated with CFA formation. Finally, 27 of 58 (46.6%) CFA-containing glomeruli in 26 cases included alpha-smooth muscle actin-positive cells in or adjacent to the CFA. CONCLUSIONS: CFAs consist of fibrous collagens in addition to matrix collagens. CFA formation is associated with older age and was observed in various kidney diseases.

Highest concentration of breast-milk-derived exosomes in colostrum.

BACKGROUND: Exosomes are nanosized extracellular vesicles, that play important roles in intercellular immune regulation. They have potential therapeutic utility for neonatal diseases including necrotizing enterocolitis. Breast-milk-derived exosomes have recently shown beneficial effects on intestinal damage in vitro and in vivo. However, the chronological change in breast-milk-derived exosome concentrations after delivery are unclear. METHODS: In this prospective study, we enrolled 17 mothers who delivered premature infants admitted to a neonatal intensive care unit in Japan. We measured the consecutive concentrations of breast-milk-derived exosomes in the mothers for 48 weeks after delivery. RESULTS: The median concentration of breast-milk-derived exosomes was 1.62 × 108 particles/ml in colostrum, showing a significant decrease after 2 weeks (P < 0.01). There was no association between the exosome concentration in colostrum and maternal perinatal factors including parity, mode of delivery, maternal age, and gestational age at delivery. CONCLUSIONS: We concluded that breast-milk-derived exosomes were the richest in colostrum. Our basic data regarding breast-milk-derived exosomes are expected to aid in the clinical application of exosomes for treating neonatal diseases.

Chronological changes of serum exosome in preterm infants: A prospective study.

BACKGROUND: Exosomes, which are observed in all human fluid, including serum, are nanosized extracellular vesicles with a mechanism of intercellular communication. Potential clinical applications of exosomes in neonatal diseases have recently been discussed. However, the characteristics of exosomes in serum during early infancy is unclear. METHODS: In this prospective study, we evaluated the chronological changes in the concentration of serum-derived exosomes of 20 infants for 12 months after birth. RESULTS: The average concentration of serum-derived exosomes was 4.6 × 1010 particles/mL at birth and increased significantly until the age of 48 weeks. There was a moderate correlation between the gestational age and the concentration of serum-derived exosomes both at birth (r = 0.54, P = 0.01) and during the 8 weeks after birth (r = 0.48, P < 0.001). A multivariable analysis showed that gestational age at birth was associated with the concentration of serum-derived exosomes at birth (partial regression coefficient, 0.86; 95% confidence interval, 0.37-1.37; P = 0.002). CONCLUSIONS: The concentration of serum-derived exosomes in preterm infants increased both chronologically and by gestational age after birth. These basic data may help to further understand physiology of exosomes in preterm infants.