Amino Acid Formula Containing Synbiotics in Infants with Cow’s Milk Protein Allergy: A Systematic Review and Meta-Analysis

Cow’s milk protein allergy (CMPA) is associated with dysbiosis of the infant gut microbiome, with allergic and immune development implications. Studies show benefits of combining synbiotics with hypoallergenic formulae, although evidence has never been systematically examined. This review identified seven publications of four randomised controlled trials comparing an amino acid formula (AAF) with an AAF containing synbiotics (AAF-Syn) in infants with CMPA (mean age 8.6 months; 68% male, mean intervention 27.3 weeks, n = 410). AAF and AAF-Syn were equally effective in managing allergic symptoms and promoting normal growth. Compared to AAF, significantly fewer infants fed AAF-Syn had infections (OR 0.35 (95% CI 0.19–0.67), p = 0.001). Overall medication use, including antibacterials and antifectives, was lower among infants fed AAF-Syn. Significantly fewer infants had hospital admissions with AAF-Syn compared to AAF (8.8% vs. 20.2%, p = 0.036; 56% reduction), leading to potential cost savings per infant of £164.05–£338.77. AAF-Syn was associated with increased bifidobacteria (difference in means 31.75, 95% CI 26.04–37.45, p < 0.0001); reduced Eubacterium rectale and Clostridium coccoides (difference in means −19.06, 95% CI −23.15 to −14.97, p < 0.0001); and reduced microbial diversity (p < 0.05), similar to that described in healthy breastfed infants, and may be associated with the improved clinical outcomes described. This review provides evidence that suggests combining synbiotics with AAF produces clinical benefits with potential economic implications.     

Multinutrient Biofortification of Maize (Zea mays L.) in Africa: Current Status,Opportunities and Limitations

Macro and micronutrient deficiencies pose serious health challenges globally, with the largest impact in developing regions such as subSaharan Africa (SSA), Latin America and South Asia. Maize is a good source of calories but contains low concentrations of essential nutrients. Major limiting nutrients in maize-based diets are essential amino acids such as lysine and tryptophan, and micronutrients such as vitamin A, zinc (Zn) and iron (Fe). Responding to these challenges, separate maize biofortification programs have been designed worldwide, resulting in several cultivars with high levels of provitamin A, lysine, tryptophan, Zn and Fe being commercialized. This strategy of developing single-nutrient biofortified cultivars does not address the nutrient deficiency challenges in SSA in an integrated manner. Hence, development of maize with multinutritional attributes can be a sustainable and cost-effective strategy for addressing the problem of nutrient deficiencies in SSA. This review provides a synopsis of the health challenges associated with Zn, provitamin A and tryptophan deficiencies and link these to vulnerable societies; a synthesis of past and present intervention measures for addressing nutrient deficiencies in SSA; and a discussion on the possibility of developing maize with multinutritional quality attributes, but also with adaptation to stress conditions in SSA.     

Rational Use of Protein Supplements in the Elderly—Relevance of Gastrointestinal Mechanisms

Protein supplements are increasingly used by older people to maintain nutrition and prevent or treat loss of muscle function. Daily protein requirements in older people are in the range of 1.2 gm/kg/day or higher. Many older adults do not consume this much protein and are likely to benefit from higher consumption. Protein supplements are probably best taken twice daily, if possible soon after exercise, in doses that achieve protein intakes of 30 gm or more per episode. It is probably not important to give these supplements between meals, as we have shown no suppressive effects of 30 gm whey drinks, and little if any suppression of 70 gm given to older subjects at varying time intervals from meals. Many gastrointestinal mechanisms controlling food intake change with age, but their contributions to changes in responses to protein are not yet well understood. There may be benefits in giving the supplement with rather than between meals, to achieve protein intakes above the effective anabolic threshold with lower supplement doses, and have favourable effects on food-induced blood glucose increases in older people with, or at risk of developing, type 2 diabetes mellitus; combined protein and glucose drinks lower blood glucose compared with glucose alone in older people.     

Dampened Muscle mTORC1 Response Following Ingestion of High-Quality Plant-Based Protein and Insect Protein Compared to Whey

Increased amino acid availability acutely stimulates protein synthesis partially via activation of mechanistic target of rapamycin complex 1 (mTORC1). Plant-and insect-based protein sources matched for total protein and/or leucine to animal proteins induce a lower postprandial rise in amino acids, but their effects on mTOR activation in muscle are unknown. C57BL/6J mice were gavaged with different protein solutions: whey, a pea–rice protein mix matched for total protein or leucine content to whey, worm protein matched for total protein, or saline. Blood was drawn 30, 60, 105 and 150 min after gavage and muscle samples were harvested 60 min and 150 min after gavage to measure key components of the mTORC1 pathway. Ingestion of plant-based proteins induced a lower rise in blood leucine compared to whey, which coincided with a dampened mTORC1 activation, both acutely and 150 min after administration. Matching total leucine content to whey did not rescue the reduced rise in plasma amino acids, nor the lower increase in mTORC1 compared to whey. Insect protein elicits a similar activation of downstream mTORC1 kinases as plant-based proteins, despite lower postprandial aminoacidemia. The mTORC1 response following ingestion of high-quality plant-based and insect proteins is dampened compared to whey in mouse skeletal muscle.     

Longitudinal Changes in the Concentration of Major Human Milk Proteins in the First Six Months of Lactation and Their Effects on Infant Growth

Our knowledge related to human milk proteins is still limited. The present study determined the changes in multiple human milk proteins during the first six months of lactation, investigated the influencing factors of milk proteins, and explored the impact of milk proteins on infant growth. A total of 105 lactating women and their full-term infants from China were prospectively surveyed in this research. Milk samples were collected at 1–5 days, 8–14 days, 1 month, and 6 months postpartum. Concentrations of total protein and α-lactalbumin were measured in all milk samples, and concentrations of lactoferrin, osteopontin, total casein, β-casein, α_s−1 casein, and κ-casein were measured in milk from 51 individuals using ultra performance liquid chromatography coupled with mass spectrometry. The concentration of measured proteins in the milk decreased during the first six months of postpartum (p-trend < 0.001). Maternal age, mode of delivery, maternal education, and income impacted the longitudinal changes in milk proteins (p-interaction < 0.05). Concentrations of α_s−1 casein in milk were inversely associated with the weight-for-age Z-scores of the infants (1 m: r −0.29, p 0.038; 6 m: r −0.33, p 0.020). In conclusion, the concentration of proteins in milk decreased over the first six months postpartum, potentially influenced by maternal demographic and delivery factors. Milk protein composition may influence infant weights.     

Plasma and Urinary Amino Acid-Derived Catabolites as Potential Biomarkers of Protein and Amino Acid Deficiency in Rats

Objective: Dietary intakes must cover protein and essential amino acid (EAA) requirements. For this purpose, different methods have been developed such as the nitrogen balance method, factorial method, or AA tracer studies. However, these methods are either invasive or imprecise, and the Food and Agriculture Organization of the United Nations (FAO, 2013) recommends new methods and, in particular, metabolomics. The aim of this study is to determine total protein/EAA requirement in the plasma and urine of growing rats. Methods: 36 weanling rats were fed with diets containing 3, 5, 8, 12, 15, and 20% protein for 3 weeks. During experimentation, urine was collected using metabolic cages, and blood from the portal vein and vena was taken at the end of the experiment. Metabolomics analyses were performed using LC-MS, and the data were analyzed with a multivariate analysis model, partial least Squares (PLS) regression, and independent component-discriminant analysis (ICDA). Each discriminant metabolite identified by PLS or ICDA was tested by one-way ANOVA to evaluate the effect of diet. Results: PLS and ICDA allowed us to identify discriminating metabolites between different diet groups. Protein deficiency led to an increase in the AA catabolism enzyme systems inducing the production of breakdown metabolites in the plasma and urine. Conclusion: These results indicate that metabolites are specific for the state of EAA deficiency and sufficiency. Some types of biomarkers such as AA degradation metabolites appear to be specific candidates for protein/EAA requirement.     

A Three-Year Longitudinal Study Comparing Bone Mass,Density, and Geometry Measured by DXA,pQCT, and Bone Turnover Markers in Children with PKU Taking L-Amino Acid or Glycomacropeptide Protein Substitutes

In patients with phenylketonuria (PKU), treated by diet therapy only, evidence suggests that areal bone mineral density (BMDa) is within the normal clinical reference range but is below the population norm. Aims: To study longitudinal bone density, mass, and geometry over 36 months in children with PKU taking either amino acid (L-AA) or casein glycomacropeptide substitutes (CGMP-AA) as their main protein source. Methodology: A total of 48 subjects completed the study, 19 subjects in the L-AA group (median age 11.1, range 5–16 years) and 29 subjects in the CGMP-AA group (median age 8.3, range 5–16 years). The CGMP-AA was further divided into two groups, CGMP100 (median age 9.2, range 5–16 years) (n = 13), children taking CGMP-AA only and CGMP50 (median age 7.3, range 5–15 years) (n = 16), children taking a combination of CGMP-AA and L-AA. Dual X-ray absorptiometry (DXA) was measured at enrolment and 36 months, peripheral quantitative computer tomography (pQCT) at 36 months only, and serum blood and urine bone turnover markers (BTM) and blood bone biochemistry at enrolment, 6, 12, and 36 months. Results: No statistically significant differences were found between the three groups for DXA outcome parameters, i.e., BMDa (L2–L4 BMDa g/cm²), bone mineral apparent density (L2–L4 BMAD g/cm³) and total body less head BMDa (TBLH g/cm²). All blood biochemistry markers were within the reference ranges, and BTM showed active bone turnover with a trend for BTM to decrease with increasing age. Conclusions: Bone density was clinically normal, although the median z scores were below the population mean. BTM showed active bone turnover and blood biochemistry was within the reference ranges. There appeared to be no advantage to bone density, mass, or geometry from taking a macropeptide-based protein substitute as compared with L-AAs.     

XPO4、MAP2K4及ZIC1在子宫内膜癌组织表达及其对子宫内膜癌患者预后评估价值

目的探讨输出蛋白(XPO)4、丝裂原活化蛋白激酶(MAP2K)4及小脑锌指结构蛋白(ZIC)1在子宫内膜癌(EC)组织中的表达及其对EC患者的预后评估价值。 方法选择2017年6月至2018年6月,无锡市妇幼保健院、复旦大学附属中山医院青浦分院收治的147例EC患者为研究对象。采用免疫组化染色法检测患者EC组织及癌旁正常组织XPO4、MAP2K4、ZIC1表达水平。采用χ²检验,对患者EC组织及癌旁正常组织XPO4、MAP2K4、ZIC1阳性率,以及不同临床病理特征患者EC组织XPO4、MAP2K4、ZIC1阳性率进行比较。采用Two-stage检验,对EC组织XPO4、MAP2K4、ZIC1呈阳性与呈阴性患者的3年总体生存(OS)率进行比较。本研究遵循的程序经过无锡市妇幼保健院、复旦大学附属中山医院青浦分院伦理委员会批准(审批文号：20160803、20160502)。 结果①本组患者EC组织XPO4、MAP2K4阳性率分别为34.7%(51/147)、38.1%(56/147),显著低于癌旁正常组织的66.7%(98/147)与72.8%(107/147),并且差异均有统计学意义(χ²＝30.060、35.812,P<0.001)。本组患者EC组织ZIC1阳性率为72.1%(106/147),显著高于癌旁正常组织的40.1%(59/147),并且差异亦有统计学意义(χ²＝30.512、P<0.001)。②不同年龄、EC直径及绝经与否患者的EC组织XPO4、MAP2K4、ZIC1阳性率比较,差异均无统计学意义(P>0.05)。不同国际妇产科联盟(FIGO)临床分期、组织病理学分级、子宫肌层侵犯程度及淋巴结转移与否患者EC组织XPO4、MAP2K4、ZIC1阳性率分别比较,差异均有统计学意义(P<0.05)。③本组EC组织XPO4、MAP2K4呈阴性患者的3年OS率分别为42.7%、38.5%,均显著低于XPO4、MAP2K4呈阳性者的68.6%、71.4%,并且差异均有统计学意义(χ²＝8.960、P＝0.003,χ²＝15.077、P<0.001)。EC组织ZIC1呈阳性患者3年OS率为35.8%,显著低于ZIC1呈阴性者的68.3%,并且差异亦有统计学意义(χ²＝12.579、P<0.001)。 结论在EC组织中,XPO4、MAP2K4呈低表达,而ZIC1则呈高表达。XPO4、MAP2K4、ZIC1表达水平与患者组织病理学分级、淋巴结转移、FIGO临床分期、子宫肌层侵犯及3年OS率显著相关,其在评估EC患者发病、进展及预后中具有一定价值。     

高迁移率族蛋白B1多态性与肺癌化疗患者肺部感染严重程度的相关性

目的探讨高迁移率族蛋白B1(HMGB1)多态性和血清表达与肺癌化疗患者肺部感染及其严重程度的关系。方法选择2018年3月-2020年1月商丘市第一人民医院肿瘤内科收治的晚期肺癌化疗患者118例作为研究对象,根据其化疗期间是否发生肺部感染分为感染组(n=57)及非感染组(n=61)。采用聚合酶链式扩增反应(PCR)对两组患者外周血HMGB1 rs1412125(T>C)、HMGB1 rs2249825(C>G)进行基因分型,分析感染组HMGB1不同基因型患者、C-反应蛋白(CRP)、降钙素原(PCT)水平及肺部感染严重程度评分(Pneumonia severity index,PSI)。结果感染组HMGB1 rs1412125位点CC基因型、C等位基因频率, rs2249825位点GG基因型、G等位基因频率均显著高于非感染组(P<0.05);校正性别、年龄等因素后,多元Logistic回归结果显示,HMGB1 rs1412125位点CC基因型、C等位基因,rs2249825位点GG基因型、G等位基因是本地区晚期肺癌化疗患者肺部感染的危险因素;感染组患者HMGB1 rs1412125位点CC型血清HMGB1、CRP、PCT水平及PSI评分均高于TT型及TC型(P<0.05),感染组患者HMGB1 rs2249825位点GG型血清HMGB1、CRP、PCT水平及PSI评分高于CG型及CC型(P<0.05)。结论 HMGB1 rs1412125位点、HMGB1 rs2249825位点多态性与本地区肺癌化疗患者肺部感染易感性及严重程度有关,HMGB1 rs1412125位点CC型、HMGB1 rs2249825位点GG型为易感基因型。