Formula Milk Supplementation and Bone Acquisition in 4-6 Years Chinese Children: A 12-Month Cluster-Randomized Controlled Trial.

Dairy foods are crucial for adequate calcium intake in young children, but scarce data are available on the effects of formula milk on bone acquisition. This cluster-randomized controlled trial investigated the effects of the supplementation of formula milk on bone health in rural children accustomed to a low-calcium diet between September 2021 and September 2022. We recruited 196 healthy children aged 4-6 years from two kindergartens in Huining County, Northwest China. A class-based randomization was used to assign them to receive 60 g of formula milk powder containing 720 mg calcium and 4.5 µg vitamin D or 20-30 g of bread per day for 12 months, respectively. Bone mineral density (BMD) and bone mineral content (BMC) at the left forearm and calcaneus, bone biomarkers, bone-related hormones/growth factors, and body measures were determined at baseline, 6, and 12 months. A total of 174 children completed the trial and were included in the analysis. Compared with the control group, formula milk intervention showed significant extra increments in BMD (3.77% and 6.66%) and BMC (4.55% and 5.76%) at the left forearm at 6th and 12th months post-intervention (all p < 0.001), respectively. Similar trends were observed in BMD (2.83%) and BMC (2.38%) in the left calcaneus at 6 months (p < 0.05). The milk intervention (vs. control) also showed significant changes in the serum concentrations of osteocalcin level (-7.59%, p = 0.012), 25-hydroxy-vitamin-D (+5.54%, p = 0.001), parathyroid hormone concentration (-15.22%, p = 0.003), and insulin-like growth factor 1 (+8.36%, p = 0.014). The percentage increases in height were 0.34%, 0.45%, and 0.42% higher in the milk group than in the control group after 3-, 6-, and 9-month intervention, respectively (p < 0.05). In summary, formula milk supplementation enhances bone acquisition at the left forearm in young Chinese children.

Neurodevelopmental Outcomes and Gut Bifidobacteria in Term Infants Fed an Infant Formula Containing High sn-2 Palmitate: A Cluster Randomized Clinical Trial.

A few studies suggested high stereo-specifically numbered (sn)-2 palmitate in a formula might favor the gut Bifidobacteria of infants. The initial colonization and subsequent development of gut microbiota in early life might be associated with development and later life functions of the central nervous system via the microbiota-gut-brain axis, such as children with autism. This study aims to assess the hypothesized effect of increasing the amount of palmitic acid esterified in the sn-2 position in infant formula on neurodevelopment in healthy full-term infants and to explore the association of this effect with the altered gut Bifidobacteria. One hundred and ninety-nine infants were enrolled in this cluster randomized clinical trial: 66 breast-fed (BF group) and 133 formula-fed infants who were clustered and randomly assigned to receive formula containing high sn-2 palmitate (sn-2 group, n = 66) or low sn-2 palmitate (control group, n = 67), where 46.3% and 10.3% of the palmitic acid (PA) was sn-2-palmitate, respectively. Infants' neurodevelopmental outcomes were measured by the Ages and Stages Questionnaire, third edition (ASQ-3). Stool samples were collected for the analysis of Bifidobacteria (Trial registration number: ChiCTR1800014479). At week 16, the risk of scoring close to the threshold for fine motor skills (reference: scoring above the typical development threshold) was significantly lower in the sn-2 group than the control group after adjustment for the maternal education level (p = 0.036) but did not differ significantly versus the BF group (p = 0.513). At week 16 and week 24, the sn-2 group (week 16: 15.7% and week 24: 15.6%) had a significantly higher relative abundance of fecal Bifidobacteria than the control group (week 16: 6.6%, p = 0.001 and week 24:11.2%, p = 0.028) and did not differ from the BF group (week 16: 14.4%, p = 0.674 and week 24: 14.9%, p = 0.749). At week 16, a higher relative abundance of Bifidobacteria was associated with the decreased odds of only one domain scoring close to the threshold in the formula-fed infants group (odds ratio (OR), 95% confidence interval (CI): 0.947 (0.901-0.996)). Elevating the sn-2 palmitate level in the formula improved infants' development of fine motor skills, and the beneficial effects of high sn-2 palmitate on infant neurodevelopment was associated with the increased gut Bifidobacteria level.

[Relations between serum adipocyte fatty acid-binding protein and type 2 diabetes in a community population].

OBJECTIVE: To study the relationship between the serum levels of adipocyte fatty acid-binding protein (A-FABP) level and type 2 diabetes mellitus in a community population. METHODS: A total of 255 residents (aged 45-85 years) were randomly selected from 4 communities in Guangzhou to examine the fasting plasma glucose (FPG), 2-hour postprandial blood glucose (2hPG), glycosylated hemoglobin (HbA1c), body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), blood pressure (BP), triglyceride (TG), cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). The insulin resistance index (HOMA-IR) was calculated and enzyme-linked immunosorbent assay (ELISA) was used to determine serum A-FABP and fasting insulin (FINs) levels. The cases were divided into 3 groups according to blood glucose level, namely the normal group (group A, n=90), impaired glucose tolerance group (group B, n=85), and diabetic group (group C, n=80), and the A-FABP levels were compared between them. RESULTS: Compared with group A, the subjects in groups B and C showed significantly increased FPG, 2hPGh, HbA1C, HOMA-IR, systolic blood pressure (SBP), and waist circumference (P=0.000) as well as FINs, WHR, diastolic blood pressure (DBP) , TG, and HDL-C (P=0.038, 0.047, 0.01, and 0.046, respectively). Compared with group B, group C showed significantly higher FPG, 2hPG, HbA1c, TG, and SBP (P=0.00), with also higher levels of FINs, BMI, WC, DBP, and HDL-C (P=0.012, 0.006, 0.03, 0.019, and 0.029, respectively). A-FABP increased significantly in the order of group A, B, and C (P=0.00), and this result was not affected by the differences in age between the 3 groups (P>0.05). A-FABP level was positively correlated to FPB, 2hPG, FINS, WHR, BMI, WC, SBP, and HOMA-IR, but inversely to TG and HDL-C (P=0.00). CONCLUSION: Elevated serum A-FABP is closely related to glucose metabolism disorder, and A-FABP may serve as a useful marker for the occurrence and development of type 2 diabetes in the community population.

Efficient intracellular delivery of functional proteins using cationic polymer core/shell nanoparticles.

Cationic core/shell nanoparticles self-assembled from biodegradable, cationic and amphiphilic copolymer poly{N-methyldietheneamine sebacate)-co-[(cholesteryl oxocarbonylamido ethyl) methyl bis(ethylene) ammonium bromide] sebacate}, P(MDS-co-CES), were fabricated and employed to deliver lectin A-chain, an anticancer glycoprotein. Lectin A-chain was efficiently bound onto the surfaces of the nanoparticles at high mass ratios of nanoparticles to lectin A-chain. The nanoparticle/lectin A-chain complexes had an average size of approximately 150 nm with zeta potential of about +30 mV at the mass ratio of 50 or above while the BioPorter/lectin A-chain complexes had a larger particle size and relatively lower zeta potential (150 nm vs. 455 nm; +30 mV vs. +20 mV). Therefore, the cellular uptake of nanoparticle/lectin A-chain complexes was much greater than that of BioPorter/lectin A-chain complexes. The results obtained from cytotoxicity tests show that lectin A-chain delivered by the nanoparticles was significantly more toxic against MDA-MB-231, HeLa, HepG2 and 4T1 cell lines when compared to BioPorter, and IC50 of lectin A-chain delivered by the nanoparticles was 0.2, 0.5, 10 and 50 mg/l, respectively, while that of lectin A-chain delivered by BioPorter was higher than 100 mg/l in all cell lines tested. These nano-sized particles may provide an efficient approach for intracellular delivery of biologically active proteins.

Co-delivery of drugs and DNA from cationic core-shell nanoparticles self-assembled from a biodegradable copolymer.

Non-viral gene-delivery systems are safer to use and easier to produce than viral vectors, but their comparatively low transfection efficiency has limited their applications. Co-delivery of drugs and DNA has been proposed to enhance gene expression or to achieve the synergistic/combined effect of drug and gene therapies. Attempts have been made to deliver drugs and DNA simultaneously using liposomes. Here we report cationic core-shell nanoparticles that were self-assembled from a biodegradable amphiphilic copolymer. These nanoparticles offer advantages over liposomes, as they are easier to fabricate, and are more readily subject to modulation of their size and degree of positive charge. More importantly, they achieve high gene-transfection efficiency and the possibility of co-delivering drugs and genes to the same cells. Enhanced gene transfection with the co-delivery of paclitaxel has been demonstrated by in vitro and in vivo studies. In particular, the co-delivery of paclitaxel with an interleukin-12-encoded plasmid using these nanoparticles suppressed cancer growth more efficiently than the delivery of either paclitaxel or the plasmid in a 4T1 mouse breast cancer model. Moreover, the co-delivery of paclitaxel with Bcl-2-targeted small interfering RNA (siRNA) increased cytotoxicity in MDA-MB-231 human breast cancer cells.