Nutritional Management for Intolerance to Human Milk Fortifier in a Preterm Small-for-Gestational-Age Infant: a Case Report.

Adequate nutrition is extremely crucial for the growth and development of preterm, small-for-gestational-age (SGA) infants owing to an increased risk of postnatal growth failure and poor neurodevelopmental outcome. Despite the beneficial properties of human milk (HM), it should be fortified to prevent extrauterine growth restriction; however, fortification of HM with a bovine-based human milk fortifier (BHMF) may induce feeding intolerance (FI) and necrotizing enterocolitis in preterm newborns. Herein, we have described the nutritional management of a preterm SGA newborn with intolerance to BHMF. A male infant was born at a gestational age of 32 weeks and 5 days, SGA weighing 1,490 grams (< 10th percentile). During BHMF use, he presented with symptoms of FI including abdominal distention, increased gastric residuals, and delayed enteral feeding advancement. Therefore, HM was fortified with carbohydrate powder, whey protein powder, and medium-chain triglycerides oil instead of BHMF to prevent FI and promote weight gain. Caloric density of feeds was increased once every 3 or 4 days by approximately 5 kcal/kg/day until an intake of 100 kcal/kg/day was achieved. Subsequently, his caloric and protein intake increased, growth rate improved, and full enteral feeding was achieved without any further symptom of FI. In conclusion, the symptoms of FI with BHMF in a preterm SGA neonate improved with the administration of a macronutrient fortified HM without compromising his enteral feed advancements, growth rate, and energy or protein intake.

Designing Tyrosinase siRNAs by Multiple Prediction Algorithms and Evaluation of Their Anti-Melanogenic Effects.

Melanin is a pigment produced from tyrosine in melanocytes. Although melanin has a protective role against UVB radiation-induced damage, it is also associated with the development of melanoma and darker skin tone. Tyrosinase is a key enzyme in melanin synthesis, which regulates the rate-limiting step during conversion of tyrosine into DOPA and dopaquinone. To develop effective RNA interference therapeutics, we designed a melanin siRNA pool by applying multiple prediction programs to reduce human tyrosinase levels. First, 272 siRNAs passed the target accessibility evaluation using the RNAxs program. Then we selected 34 siRNA sequences with ΔG ≥-34.6 kcal/mol, i-Score value ≥65, and siRNA scales score ≤30. siRNAs were designed as 19-bp RNA duplexes with an asymmetric 3' overhang at the 3' end of the antisense strand. We tested if these siRNAs effectively reduced tyrosinase gene expression using qRT-PCR and found that 17 siRNA sequences were more effective than commercially available siRNA. Three siRNAs further tested showed an effective visual color change in MNT-1 human cells without cytotoxic effects, indicating these sequences are anti-melanogenic. Our study revealed that human tyrosinase siRNAs could be efficiently designed using multiple prediction algorithms.

Role of MEK partner-1 in cancer stemness through MEK/ERK pathway in cancerous neural stem cells, expressing EGFRviii.

BACKGROUND: Glioma stem cells (GSCs) are a major cause of the frequent relapse observed in glioma, due to their high drug resistance and their differentiation potential. Therefore, understanding the molecular mechanisms governing the 'cancer stemness' of GSCs will be particularly important for improving the prognosis of glioma patients. METHODS: We previously established cancerous neural stem cells (CNSCs) from immortalized human neural stem cells (F3 cells), using the H-Ras oncogene. In this study, we utilized the EGFRviii mutation, which frequently occurs in brain cancers, to establish another CNSC line (F3.EGFRviii), and characterized its stemness under spheroid culture. RESULTS: The F3.EGFRviii cell line was highly tumorigenic in vitro and showed high ERK1/2 activity as well as expression of a variety of genes associated with cancer stemness, such as SOX2 and NANOG, under spheroid culture conditions. Through meta-analysis, PCR super-array, and subsequent biochemical assays, the induction of MEK partner-1 (MP1, encoded by the LAMTOR3 gene) was shown to play an important role in maintaining ERK1/2 activity during the acquisition of cancer stemness under spheroid culture conditions. High expression of this gene was also closely associated with poor prognosis in brain cancer. CONCLUSION: These data suggest that MP1 contributes to cancer stemness in EGFRviii-expressing glioma cells by driving ERK activity.

BCL2 induced by LAMTOR3/MAPK is a druggable target of chemoradioresistance in mesenchymal lung cancer.

Mesenchymal-type cancers after epithelial mesenchymal transition (EMT) were recently shown to acquire chemoresistance through expressing EMT specific transcription factors. However, druggable (or actionable) target(s) for chemoresistance in mesenchymal-type lung cancers remain unidentified. Here, we used a public clinical genomic database and mesenchymal lung cancer cells (MLCC) model derived from the A549 lung adenocarcinoma cell line to demonstrate that BCL2 expression, which is highly induced in mesenchymal-type lung cancers, as a predictor of poor prognosis in mesenchymal lung cancer patients and association with acquired chemoradioresistance. Thereby, combination treatment with BH3 mimetics, such as ABT-263 and ABT-737, clearly attenuated chemoresistance in MLCCs. BCL2 expression in MLCCs was induced by ERK1 activity through the upregulation of the MEK1/ERK1 scaffold protein MEK partner-1 (MP1). Interfering with the MEK1/MP1/ERK1 axis using a MEK1 inhibitor or MP1 depletion repressed BCL2 expression and sensitized MLCCs to chemoradiotherapy. Taken together, our results suggest that targeting druggable proteins in the MEK1/MP1/ERK1/BCL2 axis, such as MEK1 or BCL2, with currently available FDA approved drugs is a currently feasible approach to improve clinical outcomes of mesenchymal lung cancer patients.

Association between Urinary Sodium Excretion and Bone Health in Male and Female Adults.

BACKGROUND: High salt intake is a well-known risk factor for osteoporosis, but the association between bone mass and urinary sodium excretion has not been studied as yet. This study investigates the hypothesis that urinary sodium excretion is negatively associated with bone mass and the risk of osteoporosis. METHODS: This cross-sectional study was performed using data from the Korea National Health and Nutrition Examination Survey, 2008-2011. Participants (n = 16,279) were divided into age groups; men were categorized as younger than 50 years of age or 50 years or greater, women were categorized as pre- or post-menopausal. RESULTS: Multivariate linear regression analysis showed that urinary sodium excretion was negatively associated with bone mineral content (BMC) and bone mineral density (BMD) in premenopausal and postmenopausal women. Sodium excretion was negatively associated with BMC and BMD of the lumbar spine in women with normal bone health, osteopenia and osteoporosis, but there was no association in men. Increased sodium excretion was significantly associated with risk for osteoporosis/osteopenia in premenopausal women. CONCLUSIONS: This study demonstrates that urinary sodium excretion is negatively associated with bone health, suggesting that high salt intake could be a possible risk factor for osteoporosis in Korean women, but not in men.

Influence of preparation design on fit and ceramic thickness of CEREC 3 partial ceramic crowns after cementation.

OBJECTIVE: This study investigated the influence of preparation design on the marginal and internal gap and ceramic thickness of partial ceramic crowns (PCCs) fabricated with the CEREC 3 system. MATERIALS AND METHODS: Sixteen extracted human mandibular molars were prepared according to two different preparation designs (n = 8): a retentive preparation design with traditional cusp capping (Group I) and a non-retentive preparation design with horizontal reduction of cusps (Group II). PCCs were fabricated from IPS Empress CAD with the CEREC 3 system. The parameters for luting space and minimum occlusal ceramic thickness were set to 30 µm and 1.5 mm, respectively. The fabricated PCCs were cemented to their corresponding teeth with self-adhesive resin cement and were then scanned by micro-computed tomography. The marginal and internal gaps were measured at pre-determined measuring points in five bucco-lingual and three mesio-distal cross-sectional images. The ceramic thicknesses of the PCCs were measured at the measuring points for cusp capping areas. RESULTS: Group II (167.4 ± 76.4 µm) had a smaller overall mean gap, which included the marginal and internal gap measurements, than that of Group I (184.8 ± 89.0 µm). The internal gaps were larger than the marginal gaps, regardless of preparation design. Group I presented a thinner ceramic thickness in the cusp capping areas than the minimum occlusal ceramic thickness parameter of 1.5 mm. CONCLUSION. Preparation design had an influence on fit, particularly the internal gap of the PCCs. Ceramic thickness could be thinner than the minimum ceramic thickness parameter.