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.

Study of the pharmacokinetics of eriodictyol-6-C-ß-d-glucoside, a flavonoid of rooibos (Aspalathus linearis) extract, after its oral administration in mice.

Systemic dry syndrome affects quality of life, and various effective methods are being developed for its treatment. We recently found that rooibos (Aspalathus linearis) extract activates muscarinic M3 receptor and improves dryness in mice and humans. We identified eriodictyol-6-C-ß-D-glucoside (E6CG) as the active component affecting the secretory functions of exocrine glands; however, the pharmacokinetics and distribution of E6CG in exocrine glands have not been elucidated in mice receiving rooibos extract. We have developed a quantification method using LC-MS/MS to detect E6CG without an internal standard. Experiments on C57BL/6 mice administered rooibos extract showed that E6CG was transferred into blood plasma, with its concentration levels peaking 19.3 min after treatment. Substantial levels of E6CG were detected in the submandibular, sublingual, parotid, and lacrimal glands and in the sweat glands in palm skin. This study reports that rooibos extracts containing E6CG can be used as functional foods for improving systemic dryness.

Estimation of daily selenium intake by 3- to 5-year-old Japanese children based on selenium excretion in 24-h urine samples.

To evaluate the daily Se intake of 3- to 5-year-old Japanese children, we used seventy-two urine samples collected from fifty-three children (twenty-seven male and twenty-six female) from two cities in Miyagi prefecture, Japan. For measuring low Se concentrations with high precision, accuracy and rapidity in the 24-h urine samples, we developed an instrumental neutron activation analysis (INAA) method, that is without any chemical separation, using the short-lived 77mSe (t1/2 = 17·4 s) nuclide. The estimated Se intake of the fifty-three children was 51·5 (sd 30·2) µg/d (geometric mean: 42·7 µg/d). Ten subjects (three male and seven female), successfully provided 24-h urine samples over two or three consecutive days; their Se intake was 37·4 (sd 5·9) µg/d. Based on the logarithmically transformed data of these ten subjects, the ratio of intra-/inter-individual variances of usual Se intake was 16·7 (28·0/1·7) and geometric mean was 27·7 µg/d. The 5th to 95th percentile of usual Se intake of these ten subjects was 17·5 to 40·4 µg/d, which ranged between the recommended dietary allowance and tolerable upper intake level of Se by the Dietary Reference Intakes for Japanese (2015).

Novel effects of rooibos extract on tear and saliva secretion mediated by the muscarinic acetylcholine receptor 3 in mice.

OBJECTIVES: Sicca syndrome is characterized by dry mouth and eyes and results in a reduction of the patient's quality of life. Various natural plants, including certain herbs, have long been employed to alleviate such symptoms. Rooibos grown in South Africa is one of the potent herbal plants used for the treating dry mouth. However, the precise mechanism of action by which rooibos alleviates symptoms of dryness remains unclear. METHODS: The in vivo effects of rooibos extract (RE), which comprises eriodictyol-6-C-glucoside, on the secretory function of saliva and tears were analyzed after intraoral RE administration using wild-type C57BL/6 (B6) mice. In addition, the mechanisms of RE were investigated after administration of a muscarinic acetylcholine receptor 3 (M3R) antagonist. RESULTS: Tear and saliva volumes in mice increased significantly and in a dose-dependent manner following intraoral RE administration compared to those in mice in the control group administered H2O. An experiment performed using darifenacin administration revealed that the effects of RE on secretory function were exerted via M3R. CONCLUSION: These results suggest that RE administration is an effective treatment for symptoms of dryness and may be used in clinical settings against sicca syndrome.

Poor Bifidobacterial Colonization Is Associated with Late Provision of Colostrum and Improved with Probiotic Supplementation in Low Birth Weight Infants.

This study aimed to evaluate the association between bifidobacterial colonization in low birth weight infants and perinatal factors, including the timing of initial colostrum and the effect of probiotics on this colonization. In this non-randomized controlled trial, we enrolled 98 low-birth-weight infants from a neonatal intensive care unit (NICU) in Japan. Infants were divided into three groups: group N (no intervention), group H (received non-live bifidobacteria), and group L (received live bifidobacteria). The number of bifidobacteria in the infants' stools at 1 month of age was measured using real-time polymerase chain reaction (PCR). We divided infants into "rich bifidobacteria" (≥104.8 cells/g feces) and "poor bifidobacteria" (<104.8 cells/g feces) subgroups. The ratio of "rich bifidobacteria" infants was 20/31, 34/36, and 30/30 in groups N, H, and L, respectively. In group N, the "rich bifidobacteria" group received first colostrum significantly earlier than the "poor bifidobacteria" group (1 day vs. 4 days, P < 0.05). Compared with the N group, both groups H and L had a significantly high proportion of "rich bifidobacteria" infants (P < 0.05). Bifidobacterial colonization was poor in premature infants at 1 month compared with term infants, and the level of colonization was associated with the timing of initial provision of colostrum. Providing probiotics to premature infants can improve bifidobacterial colonization.

Comparing Antimicrobial Susceptibilities among Mycoplasma pneumoniae Isolates from Pediatric Patients in Japan between Two Recent Epidemic Periods.

We compared the antimicrobial susceptibility of Mycoplasma pneumoniae isolates from pediatric patients in Japan in 2011-2012 and 2015-2016, when epidemics occurred. The antimicrobial activity of macrolides and tetracyclines against M. pneumoniae infection tended to be restored in 2015-2016. There was no change in the antimicrobial activity of quinolones against M. pneumoniae infection.

1-Kestose consumption during pregnancy and lactation increases the levels of IgA in the milk of lactating mice.

To examine the effect of dietary supplementation with 1-kestose on the IgA levels in milk, BALB/c mice were fed diets with or without 5% 1-kestose during pregnancy and lactation. The total and specific IgA levels in the milk were measured at 7 and 14 days after delivery. A two-way ANOVA with repeated measures resulted in a significant effect of 1-kestose-supplementation on total IgA concentrations (p < 0.05) and the level of anti-Bacteroides IgA (p < 0.05). A significant positive correlation was found between the mean count of Bacteroides spp. in maternal feces and the total IgA concentration in maternal milk (r = 0.55, p < 0.05), suggesting a potential link between the gut and mammary gland immune system. In conclusion, this study demonstrated the effects of dietary prebiotics on milk IgA production.

Silencing HSF1 by short hairpin RNA decreases cell proliferation and enhances sensitivity to hyperthermia in human melanoma cell lines.

BACKGROUND: Heat shock transcription factor 1 (HSF1) is a major transactivator of genes coding for heat shock proteins (Hsps). Recent studies demonstrate that HSF1 is involved in tumor initiation, maintenance, and progression by regulating the expression of Hsps and other molecular targets. However, the role of HSF1 in melanoma is largely unknown. OBJECTIVE: The aim of this study is to analyze the role of HSF1 in melanoma. METHODS: We used short hairpin RNA (shRNA) to silence HSF1 in the human melanoma MeWo cell line and investigated its effect on cell proliferation and in the efficacy of chemotherapy, hyperthermia and thermochemotherapy. RESULTS: We found that proliferation of MeWo cells treated with HSF1 shRNA was markedly reduced, and this was associated with a G1 block of the cell cycle, whereas HSF1 shRNA treatment of normal human keratinocyte HaCat cells had no effect on proliferation. Suppression of cell proliferation by silencing HSF1 was also observed in other melanoma cell lines, HMV-I and HMV-II. Furthermore, silencing HSF1 enhanced the sensitivity of MeWo cells to heat shock, yet did not affect their sensitivity to treatment with dacarbazine. CONCLUSION: These findings show that HSF1 is required for normal growth and survival of melanoma cells under heat shock conditions, and suggests that HSF1 is a promising therapeutic target in melanoma.

Efficacy of limited-duration spinal cord stimulation for subacute postherpetic neuralgia.

Excellent outcomes were achieved with spinal cord stimulation (SCS) for 7 to 10 days on 2 patients who developed postherpetic neuralgia. Both patients were within 2 to 3 months of the onset of the condition, and nerve blocks provided only temporary pain relief and drug therapies had poor efficacy. The authors believe that limited-duration SCS for subacute postherpetic neuralgia is a useful treatment approach that may prevent the pain from progressing to chronic postherpetic neuralgia.

[Efficacy of traditional herbal medicine, Yokukansan on patients with neuropathic pain].

BACKGROUND: Neuropathic pain that is the chronic, severe, and intractable pain, interferes with activities of daily living (ADL) and consequently reduces quality of life (QOL). We reported the efficacy of Yokukansan in patients with neuropathic pain, including acute herpetic pain, postherpetic neuralgia, central poststroke pain, post-traumatic spinal cord injury pain, thalamic syndrome, complex regional pain syndrome and symptomatic trigeminal neuralgia. Yokukansan was more effective compared with traditional medicines, such as tricyclic antidepressants, carbamazepine, gabapentin, and opioids etc., which are recommended to treat neuropathic pain. Recently, effects of Yokukansan is reported on the behavioral and psychological symptoms of dementia (BPSD) in elderly patients with dementia. Repeated administration of Yokukansan decreases expression of 5-hydroxytryptamine (5-HT) 2A receptors in the prefrontal cortex in mice, and Yokukansan also protects destruction of myelin sheaths in rats with thiamine deficient-induced encephalopathy. Mechanism of effectiveness of Yokukansan on neuropathic pain has not been established; however, efficacy of Yokukansan on neuropathic pain has been shown clinically. CONCLUSIONS: As far as we know, this is the first report that Yokukansan was effective on neuropathic pain. Yokukansan without serious adverse reactions may be a possible medicine for treatment of neuropathic pain in future.