PMID: 

Mol Ther Nucleic Acids. 2019 Aug 16 ;18:232-244. Epub 2019 Aug 16. PMID: 31563120

Abstract Title: 

Exosomes Derived from miR-143-Overexpressing MSCs Inhibit Cell Migration and Invasion in Human Prostate Cancer by Downregulating TFF3.

Abstract: 

Exosomes are membrane-enclosed nanovesicles that shuttle active cargoes, such as mRNAs and microRNAs (miRNAs), between different cells. Mesenchymal stem cells (MSCs) are able to migrate to the tumor sites and exert complex functions over tumor progress. We investigated the effect of human bone marrow-derived MSC (BMSC)-derived exosomal miR-143 on prostate cancer. During the co-culture experiments, we disrupted exosome secretion by the inhibitor GW4869 and overexpressed exosomal miR-143 using miR-143 plasmid. miR-143 was involved in the progression of prostate cancer via trefoil factor 3 (TFF3). Moreover, miR-143 was downregulated while TFF3 was upregulated in prostate cancer cells and tissues, and miR-143 was found to specifically inhibit TFF3 expression. Human MSC-derived exosomes enriched miR-143 and transferred miR-143 to prostate cancer cells. Furthermore, elevated miR-143 or exosome-miR-143 or silencing TFF3 inhibited the expression of TFF3, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase (MMP)-2, and MMP-9 and PC3 cell proliferation, migration, invasion, and tumor growth, whereas it promoted apoptosis. In conclusion, hMSC-derived exosomal miR-143 directly and negatively targets TFF3 to suppress prostate cancer.

read more

PMID: 

Nutrition. 2019 Aug 24 ;69:110572. Epub 2019 Aug 24. PMID: 31563826

Abstract Title: 

Maternal consumption of vegetables, fruit, and antioxidants during pregnancy and risk for childhood behavioral problems.

Abstract: 

OBJECTIVE: The aim of this pre-birth cohort study was to examine the associations between maternal intake of vegetables, fruit, and antioxidants during pregnancy and behavioral problems in Japanese children 5 y of age.METHODS: Participants were 1199 mother-child pairs. Dietary intake was assessed using a diet history questionnaire. Emotional, conduct, hyperactivity, and peer problems, as well as low prosocial behavior were assessed using the parent version of the Strengths and Difficulties Questionnaire. Adjustment was made for maternal age, gestation at baseline, region of residence, number of children, maternal and paternal education, household income, maternal depressive symptoms during pregnancy, maternal alcohol intake during pregnancy, maternal smoking during pregnancy, child's birth weight, child's sex, breastfeeding duration, and smoking in the household during the child's first year of life.RESULTS: Maternal intake of total vegetables and green and yellow vegetables during pregnancy was independently inversely associated with childhood low prosocial behavior. Maternal intake of other vegetables during pregnancy was independently inversely related to childhood hyperactivity problems and low prosocial behavior. Maternal intake of fruit and apples during pregnancy was independently inversely related to childhood hyperactivity problems. Maternal intake of citrus fruits during pregnancy was independently inversely related to childhood emotional, conduct, and hyperactivity problems. Maternal vitamin C intake during pregnancy was independently inversely associated with childhood conduct and hyperactivity problems and low prosocial behavior.CONCLUSIONS: Maternal intake of vegetables, fruit, and vitamin C during pregnancy may be preventive against any of the behavioral problems assessed here except for peer problems in Japanese children 5 y of age.

read more

PMID: 

Arch Dis Child. 2019 Sep 15. Epub 2019 Sep 15. PMID: 31523040

Abstract Title: 

Prelacteal and early formula feeding increase risk of infant hospitalisation: a prospective cohort study.

Abstract: 

OBJECTIVE: To ascertain the relationship between prelacteal feeding, early formula feeding and adverse health outcomes, especially hospitalisation during the first year of life.DESIGN: Multicentre prospective cohort study.SETTING: Six hospitals across three cities in Vietnam.PATIENTS: A total of 2030 pregnant women were recruited at 24-28 weeks of gestation and followed up at hospital discharge, 1, 3, 6 and 12 months post partum.MAIN OUTCOME MEASURES: Rates of infant hospitalisation, diarrhoea and lower respiratory tract infection during the first 12 months.RESULTS: For the final complete sample (n=1709, 84%), about one-quarter of the infants experienced diarrhoea (25.5%) or were admitted to hospital with at least one episode (24.8%), and almost half (47.6%) the cohort contracted lower respiratory tract infection by 12 months. The prevalence of prelacteal feeding was high (56.5%) while formula feeding was common (79.5%) before hospital discharge, both of which increased the risks of adverse health outcomes particularly hospitalisation by approximately 1.5-fold, with adjusted OR (95% CI) 1.43 (1.09 to 1.88) and 1.48 (1.07 to 2.05), respectively for these infants by 12 months, when compared with others who were exclusively breast fed.CONCLUSIONS: Prelacteal feeding and early formula feeding before hospital discharge are associated with higher risks of infection and hospital admission in Vietnamese infants. Support for exclusive breast feeding should be provided to mothers to avoid the adverse consequences of giving formula milk and prelateal foods.

read more

PMID: 

Eur J Pediatr. 2019 Sep 6. Epub 2019 Sep 6. PMID: 31493020

Abstract Title: 

Formula feeding increases the risk of antibiotic prescriptions in children up to 2 years: results from a cohort study.

Abstract: 

Association between the use of infant formula and risks for infants' health is seldom studied in western countries. We set up a historical cohort based on record linkage analysis, combining the data from administrative databases providing individual data. Infants receiving the second dose of pediatric immunization between 2015 and 2017 were included. The main outcome measure was antibiotic prescriptions from enrolment up to 24 months of age, by infant feeding category at enrolment. The extended Cox regression technique was used to account for recurrent events. The infants' cohort included 40,258 5-month-old infants; during the study period, 60,932 antibiotic prescriptions were filled. Compared with infants fully breastfed, children fed with both maternal milk and formula received 106 more antibiotic prescriptions per 1000 children/year, whereas infants receiving formula only had 138 excess prescriptions per 1000 children/year. The association with infant feeding was statistically significant and remained unchangedafter adjustment for common confounders (adjusted hazard ratio, HR, for complementary feeding vs full breastfeeding 1.09; 95%CI 1.05 to 1.12; formula only versus full breastfeeding adj. HR 1.12; 95%CI 1.08 to 1.16).Conclusion: In our cohort, we observed a positive association between infant formulause considered a proxy of infections antibiotic prescription rate, considered a proxy of infections. The association followed a gradient. What is Known: • Formula feeding is associated with increased morbidity and mortality even in western countries, but still, it is common. • Information on formula are seldom unbiased; thus, public perception of risks is distorted. What is New: • In a large Italian cohort of infants, formula feeding at 5 months of age results to be associated with an increased rate of antibiotic prescription (considered to be a proxy of infection) up to 24 months ofage: the association follows a dose-response relationship. • Record linkage analysis using administrative databases provides useful information at a limited cost.

read more

PMID: 

Clin Exp Pharmacol. 2016 ;6(6). Epub 2016 Nov 14. PMID: 31565540

Abstract Title: 

Formula Feeding Predisposes Gut to NSAID-Induced Small Intestinal Injury.

Abstract: 

Objectives: Breast feeding protects infants from many diseases, including necrotizing enterocolitis, peptic ulceration and infectious diarrhea. Conversely, maternal separation stress and Non-Steroidal Anti-Inflammatory Drugs (NSAID's) can induce intestinal injury and bleeding. This study aimed to evaluate in suckling rats if maternal separation/formula feeding leads to increased intestinal sensitivity to indomethacin (indo)-induced intestinal injury and to look at potential mechanisms involved.Methods: Nine-day-old rats were dam-fed or separated/trained to formula-feed for 6 days prior to indo administration (5 mg/kg/day) or saline (control) for 3 days. Intestinal bleeding and injury were assessed by measuring luminal and Fecal Hemoglobin (Hob) and jejunal histology. Maturation of the intestine was assessed by measuring luminal bile acids, jejunal sucrase, serum corticosterone, and mRNA expression of ileal Apical Sodium-Dependent Bile Acid Transporter (ASBT).Results: At 17 days, formula-fed indo-treated pups had a 2-fold increase in luminal Hb compared to formula-fed control pups and had evidence of morphological injury to the small intestinal mucosa as observed at the light microscopic level, whereas indo had no effect on dam-fed littermates. In addition, formula-fed rats had significant increases in luminal bile acid, sucrase specific activity, serum corticosterone, and expression of ASBT mRNA compared to dam-fed rats.Conclusion: Maternal separation stress may cause early intestinal maturational changes induced by corticosteroid release, including increased epithelial exposure to bile acids. These maturational changes may have a sensitizing rather than protective effect against indo-induced injury in the new-born.

read more

PMID: 

J Cell Physiol. 2019 Sep 30. Epub 2019 Sep 30. PMID: 31566731

Abstract Title: 

MiR-20a-containing exosomes from umbilical cord mesenchymal stem cells alleviates liver ischemia/reperfusion injury.

Abstract: 

Mesenchymal stem cells (MSCs) have been proved to exert considerable therapeutic effects on ischemia-reperfusion (I/R)-induced injury, but the underlying mechanism remains unknown. In this study, we aimed to explore the potential molecular mechanism underlying the therapeutic effect of MSCs-derived exosome reinforced with miR-20a in reversing liver I/R injury. Quantitative real-time polymerase chain reaction, Western blot, and IHC were carried out to compare the differential expressions of miR-20a, Beclin-I, FAS, Caspase-3, mTOR and P62 in IR rats and normal rats. TUNEL was performed to assess IR-induced apoptosis in IR rats, and luciferase assay was used to confirm the inhibitory effect of miR-20a on Beclin-I and FAS expression. Among the 12 candidate microRNAs (miRNAs), miR-486, miR-25, miR-24, miR-20a,miR-466 and miR-433-3p were significantly downregulated in I/R. In particular, miR-20a, a miRNA highly expressed in umbilical cord-derived mesenchymal stem cells, was proved to bind to the 3' UTR of Beclin-I and FAS to exert an inhibitory effect on their expressions. Since Beclin-I and FAS were aberrantly upregulated in IR, exosomes separated from UC-MSCs showed therapeutic efficacy in reversing I/R induced apoptosis. In addition, exosomes reinforced with miR-20a and separated from UC-MSCs almost fully alleviated I/R injury. Furthermore, our results showed that miR-20a could alleviate the abnormal expression of genes related to apoptosis and autophagy, such as active Caspase-3, mTOR, P62, and LC3II. This study presented detailed evidence to clarify the mechanism underlying the therapeutic efficacy of UC-MSCs in the treatment of I/R injury.

read more

PMID: 

Int J Epidemiol. 2019 Sep 28. Epub 2019 Sep 28. PMID: 31563961

Abstract Title: 

Dietary n-3 polyunsaturated fatty acids, fish intake and healthy ageing.

Abstract: 

BACKGROUND: Seafood consumption and dietary intake of n-3 polyunsaturated fatty acids (PUFA) protect from cardiovascular disease, muscle wasting and mortality; however, their role in delaying unhealthy ageing is uncertain.METHODS: A prospective cohort study with 1592 community-dwelling individuals aged≥60 years recruited in 2008-2010, and followed through 2015. Intake of seafood and n-3 PUFA [eicosapentanoic acid (EPA) and docosahexanoic acid (DHA)] was estimated using a validated diet history and food composition tables. Unhealthy ageing was assessed across the domains of physical and cognitive function, mental health, morbidity, self-rated health and vitality.RESULTS: Higher blue fish consumption was negatively associated with unhealthy ageing in 2015 [multivariateß (95% confidence interval) per interquartile range (IQR) increase of fish: -0.49 (-0.90; -0.08)] and, specifically, was associated with lower accumulation of functional impairments [-1.00 (-1.71; -0.28)] and morbidities [-0.30 (-0.73; 0.13)]. Individuals with high intakes of EPA (≥0.47 g/day)and DHA (≥0.89 g/day) presented the highest reductions in age-related deficits accumulation: -1.61 (-3.01; -0.22) and -1.34 (-2.76; 0.08), respectively. Intake of EPA and DHA were negatively associated with the accumulation of functional deficits [results per IQR increase: -0.79 (-1.64; -0.06) and -0.84 (-1.67; -0.01), respectively] and morbidities [-0.60 (-1.10; -1.11) and -0.60 (-1.09; -0.11)]. No associations were observed between n-3 PUFA and self-rated or mental health, or between white fish and unhealthy ageing.CONCLUSIONS: In this cohort of Spanish individuals with elevated intake of fish and a high adherence to the Mediterranean diet, consumption of blue fish and n-3 PUFA had a prospective protective association with deficits accumulation.

read more

PMID: 

J Allergy Clin Immunol. 2019 Aug 19. Epub 2019 Aug 19. PMID: 31437488

Abstract Title: 

Prenatal oxidative balance and risk of asthma and allergic disease in adolescence.

Abstract: 

BACKGROUND: Fetal oxidative balance (achieved when protective prenatal factors counteract sources of oxidative stress) might be critical for preventing asthma and allergic disease.OBJECTIVE: We examined prenatal intakes of hypothesized protective nutrients (including antioxidants) in conjunction with potential sources of oxidative stress in models of adolescent asthma and allergic disease.METHODS: We used data from 996 mother-child pairs in Project Viva. Exposures of interest were maternal prepregnancy body mass index and prenatal nutrients (energy-adjusted intakes of vitamins D, C, and E;β-carotene; folate; choline; and n-3 and n-6 polyunsaturated fatty acids [PUFAs]), air pollutant exposures (residence-specific third-trimester black carbon or particulate matter with a diameter of less than 2.5 μm [PM]), acetaminophen, and smoking. Outcomes were offspring's current asthma, allergic rhinitis, and allergen sensitization at a median age of 12.9 years. We performed logistic regression. Continuous exposures were log-transformed and modeled as z scores.RESULTS: We observed protective associations for vitamin D (odds ratio [OR], 0.69 [95% CI, 0.53-0.89] for allergic rhinitis), the sum of the n-3 PUFAs eicosapentaenoic acid and docosahexaenoic acid (OR, 0.81 [95% CI, 0.66-0.99] for current asthma), and the n-3 PUFAα-linolenic acid (OR, 0.78 [95% CI, 0.64-0.95] for allergen sensitization and OR, 0.80 [95% CI 0.65-0.99] for current asthma). Black carbon and PMwere associated with an approximately 30% increased risk for allergen sensitization. No multiplicative interactions were observed for protective nutrient intakes with sources of oxidative stress.CONCLUSIONS: We identified potential protective prenatal nutrients (vitamin D and n-3 PUFAs), as well as adverse prenatal pro-oxidant exposures that might alter the risk of asthma and allergic disease into adolescence.

read more

PMID: 

Biol Reprod. 2019 Sep 30. Epub 2019 Sep 30. PMID: 31566218

Abstract Title: 

Protective Effects of Astaxanthin on Lipopolysaccharide-Induced Inflammation in Bovine Endometrial Epithelial Cells.

Abstract: 

Astaxanthin (AST), a natural antioxidant carotenoid, has been shown to exert anti-inflammatory effects. However, to our knowledge, no study has specifically addressed the potential protective effects of AST against bovine endometritis. The purpose of this study was to examine whether treatment with AST could protect endometrial epithelial cells against lipopolysaccharide (LPS)-induced inflammatory injury. Treatment of bovine endometrial epithelial cell line (BEND) with AST reduced LPS-induced production of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), increased the cellular activity of superoxide dismutase (SOD) and catalase (CAT), decreased the proportion of apoptotic cells, and promoted the production of insulin-like growth factor (IGF) and epithelial growth factor (EGF). The effects of AST were mediated through the downregulation of Bcl-2associated X, apoptosis regulator (Bax), and cleaved caspase-3 and through the upregulation of B-cell lymphoma 2 (Bcl-2). Moreover, AST significantly increased the expression of the tight junction proteins claudin, cadherin-1 (CDH1), and tight junction protein 1 (TJP1), which play an essential rolein the maintenance of host endometrial defense barrier against pathogen infection. Collectively, these results demonstrated that treatment with AST protected against oxidative stress, prevented cell apoptosis, promoted BEND cells viability, and increased the production of growth factors, in addition to activating the endometrial defense barrier. Therefore, AST is a promising therapeutic agent for the prevention and treatment of endometritis. This finding is of utmost importance in the present times when the excessive use of antibiotics has resulted in the development of antibiotic-resistant bacteria.

read more

PMID: 

Biomed Res Int. 2019 ;2019:3103946. Epub 2019 Jul 25. PMID: 31428632

Abstract Title: 

Protective Effect of Astragaloside IV on Hepatic Injury Induced by Iron Overload.

Abstract: 

Suitable content of iron is essential for human body, but iron overload is associated with many kinds of diseases including chronic liver damage. Recently, researchers find that iron overload promotes hepatocyte autophagy and apoptosis. However, the mechanism of iron overload in liver damage remains unclear. In this study, Lo2 cells were selected as the research object, iron dextran was a model drug, and astragaloside IV was a therapeutic drug to explore the role of iron overload. MTT assay and Annexin/PI double staining were used to measure cell viability and apoptosis. Ultrastructure was observed by transmission electron microscopy. The expression levels of apoptosis and autophagy-related proteins were determined by real-time PCR and Western Blot. The results showed that iron dextran could significantly inhibit Lo2 cell viability and increase the apoptosis rate, while astragaloside IV could reverse the inhibition of Lo2 cell viability and decrease the apoptosis rate. Transmission electron microscopy showed a significant increase in the number of autophagosomes after administration of iron dextran, and the application of astragaloside IV reduced the production of autophagosomes. LC3II/I was significantly upregulated in the model group but decreased in the astragaloside IV treatment group, and P62 showed the opposite trend. Iron dextran significantly upregulated the expression of Bax and downregulated Bcl2, while astragaloside IV reversed this trend. Finally, the inhibition of hepcidin caused by iron dextran was counteracted by astragaloside IV. In conclusion, the experimental results show that the iron overload model mainly induces excessive autophagy and apoptosis of hepatocytes, thus causing damage to hepatocytes, but astragaloside IV plays a certain therapeutic role in reversing this damage.

read more