Publications by authors named "Ram Reifen"

64 Publications

Antimicrobial Effect of Zn Ions Governs the Microbial Quality of Donor Human Milk.

Foods 2021 Mar 17;10(3). Epub 2021 Mar 17.

Department of Food Sciences, Institute for Postharvest Technology and Food Sciences, Agricultural Research Organization (ARO), Volcani Center, Rishon LeZion 7528809, Israel.

Donor human milk (HM) obtained at HM banks is exceptionally crucial for the feeding and treatment of preterm infants. Bacterial contaminations of HM in various stages of its handling are very common and can lead to disqualification of donations or severe infections in worse cases. Hence, HM donations are subject to strict bacteriological evaluations pre- and post-pasteurization. The main contaminating species vary between countries, banks and donors and even exhibit inter-individual variation. We initiated an assessment of the bacteriological composition of HM donated by women hospitalized in a neonatal intensive care unit in Israel. The most common bacterium identified was , found in all but one of the HM samples; the presence of several species of coagulase-negative was also noted. Next, we sought to develop a platform towards antibacterial treatment using Zn ions that have recently been found to be potent against contaminants isolated from bovine milk. Zn efficiently inhibited the growth of viable aerobic population and in HM. Growth was also inhibited in other Gram-positive bacteria such as , a well-known food-borne pathogen. and cells grown in the presence of zinc were taken for microscopic evaluation, aiming to demonstrate zinc's antimicrobial mode of action morphologically. Images obtained using scanning electron microscopy indicated leakage of cellular content and cell lysis in . Besides, cells showed abnormalities in their cell surface and complete loss of flagella upon treatment with zinc. Along with the above findings, it should be noted that this was a pilot study that tested how high doses of Zn affect breast milk as a product. Further research is likely needed on the safety of consumption of Zn-treated HM in infants and older children.
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http://dx.doi.org/10.3390/foods10030637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002753PMC
March 2021

Assessing adaptive requirements and breeding potential of spelt under Mediterranean environment.

Sci Rep 2021 Mar 30;11(1):7208. Epub 2021 Mar 30.

Department of Vegetable and Field Crops, Institute of Plant Sciences, Agricultural Research Organization (ARO)-Volcani Center, 7528809, Rishon LeZion, Israel.

The rising demand for spelt wheat (Triticum aestivum ssp. spelta) as a high-value grain crop has raised interest in its introduction into non-traditional spelt growing areas. This study aimed to assess adaptive constrains of spelt under short Mediterranean season. At first screening of a wide spelt collection for phenology and allelic distribution at the photoperiod (PPD) and vernalization (VRN) loci was done. In addition an in-depth phenotypic evaluation of a selected panel (n = 20) was performed, including agronomically important traits and concentration of grain mineral (GMC) and grain protein (GPC) content. Results from both wide screening and in-depth in panel (group of 18 spelt lines and two bread wheat lines) evaluation shows that the major adaptive constraint for spelt under Mediterranean conditions is late heading, caused by day length sensitivity, as evident from phenology and allelic profile (PPD and VRN). All lines carrying the photoperiod-sensitive allele (PPD-D1b) were late flowering (> 120DH). Based on the panel field evaluations those consequently suffer from low grain yield and poor agronomic performances. As for minerals, GMC for all but Zn, significantly correlated with GPC. In general, GMC negatively correlated with yield which complicated the assessment of GMC per-se and challenge the claim for higher mineral content in spelt grains. The exceptions were, Fe and Zn, which did not correlate with yield. Spelt lines showing high Fe and Zn concentration in a high-yield background illustrate their potential for spelt wheat breeding. Improving spelt adaptation to Mediterranean environments could be mediated by introducing the insensitive-PPD-D1a allele to spelt wheat background. Following this breeding path spelt could better compete with bread wheat under short season with limited and fluctuating rain fall.
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http://dx.doi.org/10.1038/s41598-021-86276-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010017PMC
March 2021

Genetic Architecture Underpinning Yield Components and Seed Mineral-Nutrients in Sesame.

Genes (Basel) 2020 Oct 18;11(10). Epub 2020 Oct 18.

The Robert H. Smith Institute of Plant Sciences and Genetics in Agriculture, The Hebrew University of Jerusalem, Rehovot 7610001, Israel.

Genetic dissection of yield components and seed mineral-nutrient is crucial for understanding plant physiological and biochemical processes and alleviate nutrient malnutrition. Sesame ( L.) is an orphan crop that harbors rich allelic repertoire for seed mineral-nutrients. Here, we harness this wide diversity to study the genetic architecture of yield components and seed mineral-nutrients using a core-collection of worldwide genotypes and segregating mapping population. We also tested the association between these traits and the effect of seed nutrients concentration on their bio-accessibility. Wide genetic diversity for yield components and seed mineral-nutrients was found among the core-collection. A high-density linkage map consisting of 19,309 markers was constructed and used for genetic mapping of 84 QTL associated with yield components and 50 QTL for seed minerals. To the best of our knowledge, this is the first report on mineral-nutrients QTL in sesame. Genomic regions with a cluster of overlapping QTL for several morphological and nutritional traits were identified and considered as genomic hotspots. Candidate gene analysis revealed potential functional associations between QTL and corresponding genes, which offers unique opportunities for synchronous improvement of mineral-nutrients. Our findings shed-light on the genetic architecture of yield components, seed mineral-nutrients and their inter- and intra- relationships, which may facilitate future breeding efforts to develop bio-fortified sesame cultivars.
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http://dx.doi.org/10.3390/genes11101221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603122PMC
October 2020

Biofilm formation onto starch fibres by Bacillus subtilis governs its successful adaptation to chickpea milk.

Microb Biotechnol 2020 Oct 20. Epub 2020 Oct 20.

Departmet of Food Science, Institute of Postharvest Technology and Food Sciences, Agricultural Research Organization (ARO), The Volcani Center, Rishon LeZion, 7528809, Israel.

Beneficial biofilms may confer effective adaptation to food matrices that assist bacteria in enduring hostile environmental conditions. The matrices, for instance, dietary fibres of various food products, might serve as a natural scaffold for bacterial cells to adhere and grow as biofilms. Here, we report on a unique interaction of Bacillus subtilis cells with the resistant starch fibresof chickpea milk (CPM), herein CPM fibres, along with the production of a reddish-pink pigment. Genetic analysis identified the pigment as pulcherrimin, and also revealed the involvement of Spo0A/SinI pathway in modulating the observed phenotypes. Besides, through successful colonization of the CPM fibres, the wild-type cells of B. subtilis displayed enhanced survivability and resilience to environmental stress, such as heat and in vitro gastrointestinal treatments. In total, we infer that the biofilm formation on CPM fibres is an adaptation response of B. subtilis for strategic survival.
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http://dx.doi.org/10.1111/1751-7915.13665DOI Listing
October 2020

Mitigating Milk-Associated Bacteria through Inducing Zinc Ions Antibiofilm Activity.

Foods 2020 Aug 11;9(8). Epub 2020 Aug 11.

Department of Food Science, Institute for Postharvest Technology and Food Sciences, Agricultural Research Organization (ARO), Volcani Center, Rishon LeZion 7505101, Israel.

Dairy products are a sector heavily impacted by food loss, often due to bacterial contaminations. A major source of contamination is associated with the formation of biofilms by bacterial species adopted to proliferate in milk production environment and onto the surfaces of milk processing equipment. Bacterial cells within the biofilm are characterized by increased resistance to unfavorable environmental conditions and antimicrobial agents. Members of the genus are the most commonly found spoilage microorganisms in the dairy environment. It appears that physiological behavior of these species is somehow depended on the availability of bivalent cations in the environment. One of the important cations that may affect the bacterial physiology as well as survivability are Zn ions. Thus, the aim of this study was to examine the antimicrobial effect of Zn ions, intending to elucidate the potential of a zinc-based antibacterial treatment suitable for the dairy industry. The antimicrobial effect of different doses of ZnCl was assessed microscopically. In addition, expression of biofilm related genes was evaluated using RT-PCR. Analysis of survival rates following heat treatment was conducted in order to exemplify a possible applicative use of Zn ions. Addition of zinc efficiently inhibited biofilm formation by and further disrupted the biofilm bundles. Expression of matrix related genes was found to be notably downregulated. Microscopic evaluation showed that cell elongation was withheld when cells were grown in the presence of zinc. Finally, and cells were more susceptible to heat treatment after being exposed to Zn ions. It is believed that an anti-biofilm activity, expressed in downregulation of genes involved in construction of the extracellular matrix, would account for the higher sensitivity of bacteria during heat pasteurization. Consequently, we suggest that Zn ions can be of used as an effective antimicrobial treatment in various applications in the dairy industry, targeting both biofilms and vegetative bacterial cells.
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http://dx.doi.org/10.3390/foods9081094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466369PMC
August 2020

Antimicrobial Properties of Magnesium Open Opportunities to Develop Healthier Food.

Nutrients 2019 Oct 3;11(10). Epub 2019 Oct 3.

Department of Food Sciences, Institute for Postharvest Technology and Food Sciences, Agricultural Research Organization, Volcani Center, Rishon LeZion 7528809, Israel.

Magnesium is a vital mineral that takes part in hundreds of enzymatic reactions in the human body. In the past several years, new information emerged in regard to the antibacterial effect of magnesium. Here we elaborate on the recent knowledge of its antibacterial effect with emphasis on its ability to impair bacterial adherence and formation complex community of bacterial cells called biofilm. We further talk about its ability to impair biofilm formation in milk that provides opportunity for developing safer and qualitative dairy products. Finally, we describe the pronounced advantages of enrichment of food with magnesium ions, which result in healthier and more efficient food products.
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http://dx.doi.org/10.3390/nu11102363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835631PMC
October 2019

Corrigendum to "Expression of Duodenal Iron Transporter Proteins in Diabetic Patients with and without Iron Deficiency Anemia".

J Diabetes Res 2018 26;2018:1326193. Epub 2018 Dec 26.

The Kamila Gonczarowski Institute of Gastroenterology, Assaf Harofeh Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

[This corrects the article DOI: 10.1155/2018/7494821.].
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http://dx.doi.org/10.1155/2018/1326193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327267PMC
December 2018

Encapsulation of beneficial probiotic bacteria in extracellular matrix from biofilm-forming Bacillus subtilis.

Artif Cells Nanomed Biotechnol 2018 27;46(sup2):974-982. Epub 2018 May 27.

a Department of Food Quality and Safety , Institute for Postharvest Technology and Food Sciences, Agricultural Research Organization, Volcani Center , Rishon LeZion , Israel.

Probiotics, live microbial supplements, are often incorporated into foods and beverages to provide putative health benefits. To ensure their beneficial effects, these organisms must survive processing and storage of food, its passage through the upper gastrointestinal tract (GIT), and subsequent chemical ingestion processes until they reach their target organ. However, there is considerable loss of viability of probiotic bacteria in the acidic conditions of the stomach and the high bile concentration in the small intestine. Bacillus subtilis, a spore-forming non-pathogenic bacterium, recently has gained interest in its probiotic properties; it can effectively maintain a favorable balance of microflora in the GIT. In addition, B. subtilis produces an extracellular matrix that protects it from stressful environments. We suggested that the extracellular matrix produced by B. subtilis could protect other probiotic bacteria and therefore potentially could be used as a vehicle for delivering viable probiotic cells to humans. Therefore, we developed a novel cultivation system that enables co-culturing of B. subtilis along with probiotic lactic acid bacteria (LAB) by increasing production of the extracellular matrix by B. subtilis cells. Moreover, we showed that B. subtilis improved survivability of LAB during food preparation, storage and ingestion. Therefore, we believe that the results of our study will provide a novel technique of using a natural system for preservation and delivery of probiotics to humans.
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http://dx.doi.org/10.1080/21691401.2018.1476373DOI Listing
June 2019

Expression of Duodenal Iron Transporter Proteins in Diabetic Patients with and without Iron Deficiency Anemia.

J Diabetes Res 2018 6;2018:7494821. Epub 2018 Mar 6.

The Kamila Gonczarowski Institute of Gastroenterology, Assaf Harofeh Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

The role of iron transport proteins in the pathogenesis of anemia in patients with diabetes mellitus (T2DM) is still unclear. We investigated the expression of duodenal transporter proteins in diabetic patients with and without iron deficiency anemia (IDA). . Overall, 39 patients were included: 16 with T2DM and IDA (group A), 11 with T2DM without IDA (group B), and 12 controls (group C). Duodenal mucosal expression of divalent metal transporter 1 (DMT1), ferroportin 1 (FPN), hephaestin (HEPH), and transferrin receptor 1 (TfR) was evaluated by Western blotting. Chronic disease activity markers were measured as well. . FPN expression was increased in group A compared to group B and controls: 1.17 (0.72-1.46), 0.76 (0.53-1.04), and 0.71 (0.64-0.86), respectively ( = 0.011). TfR levels were over expressed in groups A and B compared to controls: 0.39 (0.26-0.61), 0.36 (0.24-0.43), and 0.18 (0.16-0.24), respectively, ( = 0.004). The three groups did not differ significantly with regard to cellular HEPH and DMT1 expression. The normal CRP and serum ferritin levels, accompanied with normal FPN among diabetic patients without IDA, do not support the association of IDA with chronic inflammatory state. . In patients with T2DM and IDA, duodenal iron transport protein expression might be dependent on body iron stores rather than by chronic inflammation or diabetes per se.
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http://dx.doi.org/10.1155/2018/7494821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859831PMC
September 2018

Enrichment of milk with magnesium provides healthier and safer dairy products.

NPJ Biofilms Microbiomes 2017 11;3:24. Epub 2017 Oct 11.

Department of Food Quality and Safety, Institute of Postharvest Technology and Food Sciences, Agricultural Research Organization (ARO) the Volcani Center, 7528809 Rishon LeZion, Israel.

Biofilms on the surfaces of milk-processing equipment are often a major source of contamination of dairy products. Members of the genus appear to be among the most commonly found bacteria in dairy farms and processing plants. species may thrive in dairy farm equipment and in dairy products since they can form robust biofilms during growth within milk. We found that fortification of milk with magnesium mitigated biofilm formation by species, and thus could notably reduce dairy product spoilage. We also show that the mode of action of Mg ions is specific to inhibition of transcription of genes involved in biofilm formation. Our further findings indicate that in the presence of Mg bacterial cells are hypersensitive to the heat pasteurization applied during milk processing. Additionally, we demonstrated that enrichment of milk with magnesium improved technological properties of milk products such as soft cheeses. Finally, we report that there is a notable increase in the intestinal bioavailability potential of magnesium from supplemented milk compared with that from non-supplemented milk.
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http://dx.doi.org/10.1038/s41522-017-0032-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636824PMC
October 2017

Guide for Current Nutrigenetic, Nutrigenomic, and Nutriepigenetic Approaches for Precision Nutrition Involving the Prevention and Management of Chronic Diseases Associated with Obesity.

J Nutrigenet Nutrigenomics 2017 8;10(1-2):43-62. Epub 2017 Jul 8.

Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara "Fray Antonio Alcalde" and Health Sciences University Center, University of Guadalajara, Guadalajara, Mexico.

Chronic diseases, including obesity, are major causes of morbidity and mortality in most countries. The adverse impacts of obesity and associated comorbidities on health remain a major concern due to the lack of effective interventions for prevention and management. Precision nutrition is an emerging therapeutic approach that takes into account an individual's genetic and epigenetic information, as well as age, gender, or particular physiopathological status. Advances in genomic sciences are contributing to a better understanding of the role of genetic variants and epigenetic signatures as well as gene expression patterns in the development of diverse chronic conditions, and how they may modify therapeutic responses. This knowledge has led to the search for genetic and epigenetic biomarkers to predict the risk of developing chronic diseases and personalizing their prevention and treatment. Additionally, original nutritional interventions based on nutrients and bioactive dietary compounds that can modify epigenetic marks and gene expression have been implemented. Although caution must be exercised, these scientific insights are paving the way for the design of innovative strategies for the control of chronic diseases accompanying obesity. This document provides a number of examples of the huge potential of understanding nutrigenetic, nutrigenomic, and nutriepigenetic roles in precision nutrition.
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http://dx.doi.org/10.1159/000477729DOI Listing
May 2018

The vicious cycle of vitamin a deficiency: A review.

Crit Rev Food Sci Nutr 2017 Nov;57(17):3703-3714

a The Center of Nutrigenomics, The Robert H. Smith Faculty of Agriculture , Food and Environment, The Hebrew University of Jerusalem , Rehovot , Israel.

Vitamin A deficiency (VAD) is a serious and widespread public health problem and the leading cause of preventable blindness in young children. It is also associated with increased rates of death from severe infections, especially in developing countries. Over the past 35 years, researchers have examined the numerous activities of vitamin A in different tissues of the human body. VAD can lead to a series of ocular symptoms, anemia, and weak resistance to infection, which can increase the severity of infectious diseases and the risk of death. Cell development, vision, growth, and normal metabolism are among the vital processes that are insufficiently supported in the presence of VAD. VAD leads to impaired tissue function especially during the developmental periods of infancy, childhood, pregnancy, and lactation. We describe a multidirectional model of VAD that demonstrates how VAD can have progressive, negative effects on vital processes of the human body throughout the life cycle. This model starts with impaired intake and its link to decreased absorption and digestion and includes outcomes such as malnutrition, inflammation, and improper growth processes, including possible mechanisms. Together, these clinical and biochemical manifestations contribute to the vicious cycle of VAD.
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http://dx.doi.org/10.1080/10408398.2016.1160362DOI Listing
November 2017

Human milk fatty acids composition is affected by maternal age.

J Matern Fetal Neonatal Med 2017 Jan 29;30(1):34-37. Epub 2016 Jun 29.

d Department of Biochemistry and Food Sciences , The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem , Jerusalem , Israel.

Human colostrums and transition milk were collected from women under the age of 37 years and women aged 37 years and older. Transition milk of the younger group had lower fat content and 10-fold higher concentrations of omega 6 FA, eicosadecanoic, and arachdonic acids. Gestational age affected the colostrum concentration of total fat and omega 3 and omega 6 FA composition only in the older group. We concluded that age may be a factor in the FA composition of human milk. This should be taken into account when planning diets for pregnant women of different ages.
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http://dx.doi.org/10.3109/14767058.2016.1140142DOI Listing
January 2017

Vitamin A and the epigenome.

Crit Rev Food Sci Nutr 2017 Jul;57(11):2404-2411

a The Robert H. Smith Faculty of Agricultural, Food, and Nutritional Sciences, The Hebrew University of Jerusalem , Rehovot , Israel.

The epigenetic phenomena refer to heritable changes in gene expression other than those in the DNA sequence, such as DNA methylation and histone modifications. Major research progress in the last few years has provided further proof that environmental factors, including diet and nutrition, can influence physiologic and pathologic processes through epigenetic alterations, which in turn influence gene expression. This influence is termed nutritional epigenetics, and one prominent example is the regulation of gene transcription by vitamin A through interaction to its nuclear receptor. Vitamin A is critical throughout life. Together with its derivatives, it regulates diverse processes including reproduction, embryogenesis, vision, growth, cellular differentiation and proliferation, maintenance of epithelial cellular integrity and immune function. Here we review the epigenetic role of vitamin A in cancer, stem cells differentiation, proliferation, and immunity. The data presented here show that retinoic acid is a potent agent capable of inducing alterations in epigenetic modifications that produce various effects on the phenotype. Medical benefits of vitamin A as an epigenetic modulator, especially with respect to its chronic use as nutritional supplement, should rely on our further understanding of its epigenetic effects during health and disease, as well as through different generations.
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http://dx.doi.org/10.1080/10408398.2015.1060940DOI Listing
July 2017

Fatty acids composition of human milk fed to small for gestational age infants.

J Matern Fetal Neonatal Med 2016 Sep 30;29(18):3041-4. Epub 2015 Nov 30.

a Departments of Neonatology and Pediatrics , Tel Aviv Medical Center , Tel Aviv , Israel .

Objectives: To test the null hypothesis that mothers of asymmetric small for gestational age (SGA) infants produce milk with fatty acids composition similar to that of lactating mothers of appropriate-for-gestational-age (AGA) infants.

Methods: We obtained human milk (HM) from 2 groups of lactating volunteers that gave birth to asymmetric SGA (study group) or AGA infants (control group). Each mother was asked to contribute by manual expression at least one of 3 samples: first 72 hours after labor (colostrum), day 2-7 postpartum (transitional milk) and 14 days post partum (mature milk). After lipid extraction using Folch's cold-extraction procedure fatty acids were analyzed using gas chromatography.

Results: A total of 108 samples were obtained in 60 women. In univariate analysis, there were no significant differences in any of the fatty acids concentrations examined between groups. This remained true when timing of the sample (colostrum, transitional or mature milk) or gestational age were introduced as confounders in analysis of variance (general linear model).

Conclusion: Fatty acid composition of human milk is not affected by whether or not the infant was fetal growth restricted. We suggest that mothers of SGA infants may be reassured about the fat quality of their milk.
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http://dx.doi.org/10.3109/14767058.2015.1114082DOI Listing
September 2016

Vitamin A exerts its antiinflammatory activities in colitis through preservation of mitochondrial activity.

Nutrition 2015 Nov-Dec;31(11-12):1402-7. Epub 2015 Jun 6.

The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Jerusalem, Israel.

Objectives: The aim of this study was to assess the protective effects of vitamin A in a rat model of colitis to elucidate a possible mechanism of action.

Methods: Male rats were fed for 21 d with either a normal diet or high vitamin A diet (5000 IU/d). On day 22, colitis was induced with 2,4,6-trinitrobenzenesulfonic acid (TNBS). Rats were sacrificed after 24 h and colonic tissue was removed for evaluation.

Results: Morphologically, in the supplemented group preservation of tissue architecture, no vasculitis or necroses were detected. Biochemically, decreased myeloperoxidase activity and protection of the mitochondria as evaluated by preserving tissue oxygen consumption, mitochondrial DNA, and expression of cytochrome c, was observed. Vitamin A supplementation also increased the levels of nuclear respiratory factor (NFR)-1 and mitochondrial transcription factor-A (TFAM) in normal colon tissue and in colon tissue under inflammatory conditions.

Conclusion: The results indicate that tissue damage in colitis is accompanied by the arrest of mitochondrial respiration, loss of mitochondrial DNA, and the expression of mitochondrial proteins. Vitamin A effectively protects colon mitochondria by upregulation of mitochondrial transcription factors, NFR-1 and TFAM, and prevents inflammatory and necrotic changes in colitis. Vitamin A is therefore a potential therapeutic agent in inflammatory bowel disease.
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http://dx.doi.org/10.1016/j.nut.2015.05.011DOI Listing
July 2016

α-Linolenic acid (ALA) is an anti-inflammatory agent in inflammatory bowel disease.

J Nutr Biochem 2015 Dec 14;26(12):1632-40. Epub 2015 Aug 14.

Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Studies suggest that consumption of omega-3 (n-3) polyunsaturated fatty acids (PUFA) plays a protective role in inflammatory bowel disease; however, the use of plant-derived oils rich in α-linolenic acid (ALA) has not been widely investigated. The aims of this study were to test the effects of two different sources of (n-3) PUFA, fish and plant-derived oils, in two animal models of experimental colitis and to determine whether the (n-3) PUFA-enriched diets could ameliorate the inflammatory status. Rats were fed diets rich in corn, fish or sage oil with or without vitamin A supplementation for 3weeks then colitis was induced by adding dextran sodium sulfate to the drinking water or by injecting 2,4,6-trinitrobenzene sulfonic acid. We show that colitic rats fed the sage oil diets had a lower inflammatory response, improved histological repair and had less necrotic damage in the mucosa when compared to the corn and fish oil groups. Colonic damage and myeloperoxidase activity were significantly lower. Colonic mRNA levels of pro-inflammatory genes including interleukin IL-6, cyclooxygenase 2 and tumor necrosis factor α were markedly down-regulated in rats fed fish and sage oils compared to control. These results were supported by experiments in the human colonic epithelial cell line Caco-2, where ALA supplementation was shown to be effective in inhibiting inflammation induced by IL-1β by down-regulating mRNA levels of pro-inflammatory genes including IL-8, COX2 and inducible nitric oxide synthase. Taken together, these results suggest that plant-derived oil rich in ALA could ameliorate the inflammatory damage in colitis.
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http://dx.doi.org/10.1016/j.jnutbio.2015.08.006DOI Listing
December 2015

Vitamin A supplementation via aerosol spray in asthmatic children.

Pediatr Allergy Immunol 2015 Sep;26(6):578-9

The Pulmonary Unit, Department of Pediatrics, Edit Wolfson Medical Center Holon, Holon, Israel.

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http://dx.doi.org/10.1111/pai.12443DOI Listing
September 2015

Past and Present Insights on Alpha-linolenic Acid and the Omega-3 Fatty Acid Family.

Crit Rev Food Sci Nutr 2016 Oct;56(14):2261-7

b Division of Cancer and Surgery, Imperial College , Chelsea and Westminster Campus , London , UK.

Alpha-linolenic acid (ALA) is the parent essential fatty acid of the omega-3 family. This family includes docosahexaenoic acid (DHA), which has been conserved in neural signaling systems in the cephalopods, fish, amphibian, reptiles, birds, mammals, primates, and humans. This extreme conservation, in spite of wide genomic changes of over 500 million years, testifies to the uniqueness of this molecule in the brain and affirms the importance of omega-3 fatty acids. While DHA and its close precursor, eicosapentaenoic acids (EPA), have received much attention by the research community, ALA, as the precursor of both, has been considered of little interest. There are many papers on ALA requirements in experimental animals. Unlike humans, rats and mice can readily convert ALA to EPA and DHA, so it is unclear whether the effect is solely due to the conversion products or to ALA itself. The intrinsic role of ALA has yet to be defined. This paper will discuss both recent and historical findings related to this distinctive group of fatty acids, and will highlight the physiological significance of the omega-3 family.
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http://dx.doi.org/10.1080/10408398.2013.828678DOI Listing
October 2016

Elevated milk β-carotene and lycopene after carrot and tomato paste supplementation.

Nutrition 2015 Mar 20;31(3):443-5. Epub 2014 Nov 20.

Institute of Biochemistry, Food Science and Nutrition, The Hebrew University of Jerusalem, Rehovot, Israel. Electronic address:

Objectives: To measure concentrations of β-carotene and lycopene in the breast milk of healthy, well-nourished, lactating women supplemented with fresh carrot or tomato paste.

Methods: Twelve women were given fresh carrot paste and another 14 were given fresh tomato paste once a day for 3 d with a high-lipid-content meal. The women were instructed to avoid any food containing β-carotene or lycopene, other than the test meal. Milk carotenoid levels were measured before, during, and after the trial. The carrot and tomato meals contained 15 mg of all-trans β-carotene and 15 mg of all-trans lycopene, respectively.

Results: We demonstrated a significant increase in milk β-carotene and elevated milk lycopene levels after the lipid-rich fresh carrot and tomato meals, respectively.

Conclusions: We suggest that breast milk carotenoid levels reflect the mother's level of intake and can thus be raised by simple nutritional intervention. The results of this study may be relevant to breast-feeding mothers of both preterm and term infants by raising antiinflammatory and antioxidant properties in their milk.
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http://dx.doi.org/10.1016/j.nut.2014.10.009DOI Listing
March 2015

Facial Expression in Response to Smell and Taste Stimuli in Small and Appropriate for Gestational Age Newborns.

J Child Neurol 2015 Oct 18;30(11):1466-71. Epub 2015 Feb 18.

Institute for Child Development and Pediatric Neurology Unit, Tel Aviv Medical Center and Tel Aviv University, Tel Aviv, Israel.

Small for gestational age newborns can later suffer from eating difficulties and slow growth. Nutritional preferences can be influenced by changes in sensory perception of smell and taste. To determine whether these could be detected at birth, the authors examined the different recognition pattern of smell and taste in small for gestational age newborns compared to appropriate for gestational age controls, as expressed by gusto-facial and naso-facial reflexes. The authors performed video analysis of facial expressions of 10 small for gestational age and 12 control newborns exposed to various tastes and smells. No difference in the facial recognition patterns for taste or smell was demonstrated between small for gestational age and controls, except for perception of distilled water. Newborns show recognizable patterns of facial expression in response to taste and smell stimuli. Perception of taste and smell in small for gestational age newborns is not different from controls, as measured by the method of facial recognition.
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http://dx.doi.org/10.1177/0883073815570153DOI Listing
October 2015

β-Carotene can reverse dysregulation of iron protein in an in vitro model of inflammation.

Immunol Res 2015 Feb;61(1-2):70-8

The Faculty of Agriculture, Food and Environmental Sciences, The School of Nutritional Sciences, The Hebrew University of Jerusalem, 76100, Rehovot, Israel.

Anemia of chronic disease is frequently seen in chronic inflammatory conditions. Its hallmark is disrupted iron homeostasis, with increased uptake and retention of iron in cells of the reticuloendothelial system. Using the Caco-2 cell line as an in vitro model for iron absorption, local intestinal iron-related protein dynamics were evaluated during interleukin (IL)1β/iron-induced inflammation, confirmed by IL8 release, and following β-carotene and vitamin A supplementation. Time- and dose-dependent iron administration to the cells was then studied. The effects on heavy and light ferritin, ferroportin, transferrin receptor and intracellular iron levels were compared in inflamed Caco-2 cells with and without application of the anti-inflammatory agents β-carotene and vitamin A. IL1β treatment led to IL8 release, a surge in both ferritins' expressions and suppression of ferroportin and transferrin receptor expression. β-Carotene significantly reduced IL8 (1,306.2-253.75 pg/ml), decreased light and heavy ferritin by 77.8 and 45.8%, respectively, and increased ferroportin by 59.9% (P < 0.05). Increasing iron concentrations and incubation periods resulted in increased IL8 release. A strong correlation was found between the levels of IL8 and the ferritins. Intracellular iron sequestration was induced by IL1β and iron and alleviated by β-carotene. β-Carotene normalized the main iron-related proteins' levels, reduced IL8 production, and released intracellular trapped iron. These results highlight local mucosal control of iron regulation and suggest that by applying anti-inflammatory compounds, less iron is locked in inflamed intestinal epithelial cells, leading to its increased bioavailability. This suggests a possible approach to combating anemia associated with chronic inflammatory conditions.
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http://dx.doi.org/10.1007/s12026-014-8570-8DOI Listing
February 2015

Food allergy and cross-reactivity-chickpea as a test case.

Food Chem 2014 Dec 4;165:483-8. Epub 2014 Jun 4.

The School of Nutritional Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environmental Sciences, The Hebrew University of Jerusalem, 76100 Rehovot, Israel. Electronic address:

Chickpea has become one of the most abundant crops consumed in the Mediterranean and also in western world. Chickpea allergy is reported in specific geographic areas and is associated with lentil and/or pea allergy. We investigated cross-reactivity between chickpea and pea/lentil/soybean/hazelnut. The IgE-binding profiles of chickpea globulin and pea/lentil/soybean/hazelnut extracts were analyzed by immunoblotting and immunoblot-inhibition studies. Inhibition-assay with pea/lentil completely suppressed IgE-binding to chickpea globulin allergens, while not so in the reciprocal inhibition. Pre-absorption of sera with chickpea globulin caused the disappearance of IgE-binding to protein on an immunoblot of soybean/hazelnut protein extract. These results suggest that cross-reactivity exists between chickpea and pea/lentil/soybean/hazelnut. Chickpea allergy is associated with lentil and/or pea allergy, but evidently may not present independently. This, together with the described asymmetric cross-reactivity and phylogenetic aspects, suggest that chickpea allergy is merely an expression of cross-reactivity, caused by pea and/or lentil as the "primary" allergen.
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http://dx.doi.org/10.1016/j.foodchem.2014.05.138DOI Listing
December 2014

The potential use of chickpeas in development of infant follow-on formula.

Nutr J 2014 Jan 22;13. Epub 2014 Jan 22.

The School of Nutritional Sciences Plant Genetics, The Hebrew University of Jerusalem, P,O, Box 12, Rehovot 76100, Israel.

Background: Undernutrition during childhood is a common disorder in the developing countries, however most research has focussed much on its treatment rather than its prevention.

Objective: We investigated the potential of using chickpeas in infant follow-on formula production against the requirements of WHO/FAO on complementary foods and EU regulations on follow-on formula.

Methods: Chickpeas were germinated for 72 hours followed by boiling, drying and dehulling in order to minimise associated anti-nutrition factors. Saccharifying enzymes were used to hydrolyse starch to maltose and the resulting flours were analysed for their protein content and amino acid profile.

Results: The protein content (percentage) increased from 16.66 ± 0.35 and 20.24 ± 0.50 to 20.00 ± 0.15 and 21.98 ± 0.80 for the processed desi and kabuli cultivar compared to raw chickpeas, respectively (P < 0.05). There was insignificant change (P = 0.05) in amino acid profile following processing and the resulting flour was found to meet the amino acid requirements of WHO/FAO protein reference for 0-24 month's children.

Conclusion: The designed chickpea based infant follow-on formula meets the WHO/FAO requirements on complementary foods and also the EU regulations on follow-on formula with minimal addition of oils, minerals and vitamins. It uses chickpea as a common source of carbohydrate and protein hence making it more economical and affordable for the developing countries without compromising the nutrition quality.
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http://dx.doi.org/10.1186/1475-2891-13-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913840PMC
January 2014

Desalination of water: nutritional considerations.

Isr Med Assoc J 2013 Apr;15(4):164-8

Department of Nutrition, Ministry of Health, Jerusalem, Israel.

Background: Desalination of seawater and brackish water (mixed seawater and freshwater) provides an increasing portion of the Israeli drinking water supply. However, desalinated water contains little calcium (Ca) and magnesium (Mg), and consumers may be at risk for deficiencies of these essential minerals.

Objectives: To assess intakes of Mg and Ca from water, other beverages, and food in communities with different water supplies, and assess the proportion of individuals with intakes below the Estimated Average Requirement (EAR).

Methods: Telephone interviews were conducted using a food frequency questionnaire to assess Mg and Ca intakes by adults in four communities. The proportion of individuals with Mg and Ca intakes below the EAR were evaluated based on current intakes and on potential intakes assuming that desalinated water had been introduced countrywide.

Results: The proportion of individuals with Mg intake below the EAR was higher in Kibbutz Maagan Michael (30.6%), an agricultural settlement supplied with desalinated water, than in Hadera (16.7%), a city supplied by the National Water Carrier (NWC) (P < 0.05). The proportion of individuals with Ca intake below the EAR was higher in Maagan Michael (61.7%) than in the communities supplied with water from the NWC or mixed water (37.9%-48.2%), P < 0.05.

Conclusions: Returning Mg and Ca to desalinated water may be beneficial for raising intakes in Israeli communities supplied with desalinated water. Individuals with intake of Mg and/or Ca below the EAR may be at risk for cardiac abnormalities and other medical conditions.
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April 2013

Vicilin and the basic subunit of legumin are putative chickpea allergens.

Food Chem 2013 May 2;138(1):13-8. Epub 2012 Nov 2.

The School of Nutritional Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, 76100 Rehovot, Israel.

IgE-mediated reactions to food allergens constitute a major health problem in industrialized countries. Chickpea is consumed in Mediterranean countries, and reportedly associated with IgE-mediated hypersensitivity reactions. However, the nature of allergic reactions to chickpea has not been characterized. A serum pool from paediatric patients allergic to chickpeas was used to detect IgE-binding proteins from chickpea seeds by immunoassay and immunoblot inhibition assay. Protein samples enriched in chickpea legumin and vicilin were obtained by anion exchange chromatography, and were identified by mass spectrometric analysis. IgE-immunoassays of globulin fractions from chickpeas revealed that vicilin (50 kDa) and the basic subunit of legumin (20 kDa) were bound by IgE from patient sera. Pea and lentil protein extracts strongly inhibited the IgE binding to chickpea globulin. We speculate that vicilin and the basic subunit of legumin are major chickpea allergens. Also, the globulin fraction of chickpea likely cross-reacts with the allergenic proteins of pea and lentil.
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http://dx.doi.org/10.1016/j.foodchem.2012.10.031DOI Listing
May 2013

Needle biopsy for hepatic vitamin A levels in lions (Panthera leo).

J Zoo Wildl Med 2012 Jun;43(2):207-13

Neurology and Neurosurgery Service, Hebrew University Veterinary Teaching Hospital, Koret School of Veterinary Medicine, Hebrew University of Jerusalem, P.O. Box 12, 76100 Rehovot, Israel.

Hypovitaminosis A (HA)-related skull malformations resulting in neurologic abnormalities and death have been, and still are, reported in captive lions (Panthera leo) worldwide. Liver vitamin A (VA) concentration is the most reliable indicator of animals' VA status, and its assessment is essential in prevention and treatment of HA in lions. A percutaneous needle liver biopsy using high-performance liquid chromatography ultraviolet retinoid analysis for VA concentration measurement was validated. It was first assessed in vitro using chicken liver. Later, the safety and feasibility of ultrasound-guided percutaneous needle liver biopsy was assessed in living lions. Hepatic VA concentrations in lion liver were measured using the above laboratory method. Mean chicken hepatic VA concentration in needle biopsy (NB) and wedge biopsy (WB) of the same liver lobes were 108.66 and 60.89 microg/g wet tissue, respectively, and were significantly (P = 0.03) correlated (r = 0.74). The calculated linear regression for predicting VA concentration in WB using NB VA for chicken liver was 25.194 + 0.3234x NB (microg/g). Four ultrasound-guided percutaneous needle liver biopsies were obtained from each of the four lions under general anesthesia. Mean hepatic VA concentration was 8.25 microg/g wet tissue (range 1.43-25.29 microg/g). Mean serum VA concentration, measured in these four lions was 1,011.1 nmol/L with a standard deviation of 337.91 nmol/L (range 590.26-1,077.2 nmol/L). The lions recovered uneventfully, and no complications were observed during a 4-yr follow-up period. In conclusion, the percutaneous needle liver biopsy technique is a reliable, practical, safe tool for obtaining liver tissue samples antemortem for assessment of the VA status in lions and can be used in future studies.
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http://dx.doi.org/10.1638/2010-0038.1DOI Listing
June 2012

Dietary acculturation and increasing rates of obesity in Ethiopian women living in Israel.

Nutrition 2012 Jan 18;28(1):30-4. Epub 2011 Jul 18.

The Hebrew University of Jerusalem, The Robert H. Smith Faculty of Agriculture, Food and Environment, Institute of Biochemistry, Food Science and Nutrition, Rehovot, Israel.

Objective: Immigration from Third World countries to the developed world is characterized by modification of lifestyle and acculturation to local customs. This study investigated changes in nutritional status and eating behaviors in female Ethiopian immigrants in Israel.

Methods: Personal interviews, two 24-h dietary recalls, and anthropometric measurements were carried out in a random sample of 53 women 32 ± 6 y of age.

Results: After living in Israel for an average of 14 y, body mass index was similar to the general Israeli population, with 42% of participants with a body mass index greater than 24.9 kg/m², including 11% categorized as obese. This is in stark contrast to the body mass index measured at arrival in Israel (∼19-20 kg/m²). Less than optimal consumption of dietary fiber, calcium, folate, and B12 was documented. Analysis by food groups showed that intake of dairy products, fruits, and vegetables was negligible, whereas simple sugar intakes were high. The women continued to prepare traditional Ethiopian foods but also incorporated local, less healthy foods into their diets. Compared with the high energy expenditure in rural Ethiopia, participants reported minimal physical activity in Israel.

Conclusions: This immigrant community is at high risk for developing nutrition-related chronic diseases. Culturally sensitive nutrition education programs are urgently needed.
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http://dx.doi.org/10.1016/j.nut.2011.02.010DOI Listing
January 2012

Leptin administration affects growth and skeletal development in a rat intrauterine growth restriction model: preliminary study.

Nutrition 2011 Sep 25;27(9):973-7. Epub 2011 Feb 25.

School of Nutritional Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.

Objective: Skeletal abnormalities are one of the hallmarks of growth delay during gestation. The aim of this study was to determine changes induced by leptin in skeletal growth and development in a rat model of intrauterine growth retardation (IUGR) and to elucidate the possible underlying mechanisms.

Methods: Intrauterine growth retardation was induced prepartum and the effects of leptin to mothers prenatally or to offspring postnatally were studied. Radii were harvested and tested mechanically and structurally. Tibias were evaluated for growth-plate morphometry.

Results: On day 40 postpartum, total bone length and mineral density and tibial growth-plate width and numbers of cells within its zones of offspring treated with leptin were significantly greater than in the control group.

Conclusion: Postnatal leptin administration in an IUGR model improves the structural properties and elongation rate of bone. These findings could pave the way to preventing some phenotypic presentations of IUGR.
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http://dx.doi.org/10.1016/j.nut.2010.10.020DOI Listing
September 2011

Vitamin A deficiency associated with enhanced proliferation of bile duct epithelial cells in the rat.

Isr Med Assoc J 2010 Feb;12(2):82-6

Division of Pediatric Gastroenterology and Nutrition, Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel.

Background: Vitamin A and its derivative retinoic acid regulate various aspects of cell behavior as growth, differentiation, and proliferation. Retinoic acid derivative have been suggested to play a role in processes such as hepatic regeneration and fibrosis.

Objectives: To evaluate the influence of vitamin A on rat liver epithelial cell proliferation.

Methods: We performed common bile duct ligation in rats that had been subjected to differing vitamin A diets and compared their livers to control rats. Proliferation, apoptosis, and retinoic acid receptors were evaluated by histology and immunohistochemistry in bile duct cells and hepatocytes.

Results: Vitamin A deficiency was found to be associated with enhanced proliferation of bile duct epithelial cells following CBD ligation. The proliferation was manifested by increased numbers of ducts, by aberrant extended ductal morphology, and by elevated numbers of nuclei expressing the proliferation marker Ki67. The amount of vitamin A in the rat diet did not affect detectably ductal cell apoptosis. We observed up-regulated expression of the retinoid X receptor-alpha in the biliary epithelium of vitamin A-deficient rats that had undergone CBD ligation, but not in vitamin A-sufficient rats.

Conclusions: We speculate that the mechanism underlying the ductal proliferation response involves differential expression of RXR-alpha. Our observations suggest that deficiency of vitamin A may exacerbate cholestasis, due to excessive intrahepatic bile duct proliferation.
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February 2010