Nutritional Deprivation Research Articles

The interaction between neuroendocrine and immune systems in infants and children during under nutrition

Malnutrition remains an international concern because it represents a major cause of childhood morbidity and mortality. In infants and children malnutrition significant metabolic, hormonal, and immune changes occur with short- and long-term effects and outcomes. Thus, studies which contribute to the prevention, amelioration, or rehabilitation of the detrimental effect of malnutrition are necessary. Investigations on endocrine, metabolic, and immune changes related to severe malnutrition started a long time ago. However, recently there has been little work on these important changes, their mechanism/s of action and interactions, and their effect on different systems. The neuroendocrine system is the initial response to stress, so it is reasonable to assume that this system also plays a key role in the pathophysiological changes during nutritional deprivation. However, many of the newly identified functions/changes are better explained by the action of conventional neurotransmitters (e.g., glutamate and GABA) that constitute a neuronal circuit. In addition, the mechanistic Target of Rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase has emerged as a sensor for nutrients that has a central joint in cellular metabolism, cell growth, and differentiation. Its functions during malnutrition in the central nervous system, endocrine system, and different end organs and tissues (liver, pancreas, muscle, and adipose tissue) need elucidation. This article presents a brief review of neuroendocrine changes during malnutrition and their effects on the modulation of metabolism, growth, and immune functions. The pros and cons of these endocrine changes are discussed as well as their reversibility on nutritional rehabilitation.

Guanidine and Galactose Decorated Nanophotosensitizer with Oxygen Self‐Sufficient Capability for the Localized Ablation of Oral Biofilm

AbstractDental caries is a common disease caused by plaque biofilms, which are important pathogenic factors in many diseases. When hosts are overexposed to dietary sugars, pathogens such as Streptococcus mutans (S. mutans) and other cariogenic bacteria, metabolically assemble an extracellular matrix rich in exopolysaccharides to form a disease‐causing biofilm, in which the microenvironment is characterized by regional hypoxia, low pH, and nutritional deprivation. Current antimicrobials with inadequate penetration and a lack of pathogens targeting the biofilm do not degrade the protective matrix within the biofilm. In this study, a guanidine and galactose decorated nanophotosensitizer with oxygen self‐sufficient capability, p(GF/GEF)‐I, is developed to enhance the permeability of biofilms by positively charging the particle surface and easily binding to the bacteria within the membrane through electrostatic interactions. 90% of the biofilm on enamel surface is eliminated after treatment with p(GF/GEF)‐I under laser irradiation. Notably, the nanophotosensitizer inhibits the recolonization of dental biofilms by S. mutans, preventing secondary infections. Furthermore, dental caries in a rodent model are reduced with exposure to nanophotosensitizer. p(GF/GEF)‐I is a significantly higher efficacy without damaging the surrounding soft tissue. With further development and optimization, p(GF/GEF)‐I shows significant potential as a phototherapeutic agent for the treatment of biofilm‐induced diseases.

Investigating the unaccounted ones: insights on age-dependent reproductive loss in a viviparous fly

Most empirical and theoretical studies on reproductive senescence focus on observable attributes of offspring produced, such as size or postnatal survival. While harder to study, an important outcome of reproduction for a breeding individual is whether a viable offspring is produced at all. While prenatal mortality can sometimes be directly observed, this can also be indicated through an increase in the interval between offspring production. Both direct reproductive loss and presumed losses have been found to increase in older females across several species. Here, we study such reproductive loss (or “abortion”) in tsetse, a viviparous and relatively long-lived fly with high maternal allocation. We consider how age-dependent patterns of abortion depend on the developmental stage of offspring and find that, as per previous laboratory studies, older females have higher rates of abortion at the late-larval stage, while egg-stage abortions are high both for very young and older females. We track the reproductive output of individual females and find little evidence that experiencing an abortion is an adaptive strategy to improve future reproductive outcomes. After an abortion, females do not generally take less time to produce their next offspring, these offspring are not larger, and there is no sex bias towards females, the sex with presumed higher fitness returns (being slightly larger and longer-lived than males, and with high insemination rates). Abortion rates are higher for breeding females experiencing stress, measured as nutritional deprivation, which echoes previous work in tsetse and other viviparous species, i.e., humans and baboons. We discuss our results in the context of studies on reproductive loss across taxa and argue that this is an important yet often overlooked reproductive trait which can vary with maternal age and can also depend on environmental stressors.

Clonal mesenchymal stem cell-derived extracellular vesicles improve mouse model of weight drop-induced traumatic brain injury through reducing cistauosis and apoptosis

ObjectiveTraumatic brain injury (TBI) is a major risk factor for disabilities globally with no effective treatment thus far. Recently, homogenous population of clonal mesenchymal stem cells (cMSC) and their derived extracellular vesicles (cMSC-EVs) have been proposed as a promising TBI treatment strategy. We herein investigated possible therapeutic effect of cMSC-EVs in TBI treatment and the underlying mechanisms considering cis p-tau as an early hallmark of TBI. MethodsWe examined the EVs morphology, size distribution, marker expression, and uptake. Moreover, the EVs neuroprotective effects were studied in both in-vitro and in-vivo model. We also examined the anti-cis p-tau antibody-loading characteristics of the EVs. We treated TBI mouse model with EVs; prepared from cMSC-conditioned media. TBI mice were given cMSC-EVs intravenously and their cognitive functions were analyzed two months of the treatment. We employed immunoblot analysis to study the underlying molecular mechanisms. ResultsWe observed a profound cMSC-EVs uptake by primary cultured neurons. We found a remarkable neuroprotective effect of cMSC-EVs upon nutritional deprivation stress. Furthermore, cMSC-EVs were effectively loaded with an anti-cis p-tau antibody. There was a significant improvement in cognitive function in TBI animal models treated with cMSC-EVs compared to the saline-treated group. There was a decreased cis p-tau and cleaved caspase3 as well as increased p-PI3K in all treated animals. ConclusionsThe results revealed that cMSC-EVs efficiently improved animal behaviors after TBI by reducing cistauosis and apoptosis. Moreover, the EVs can be employed as an effective strategy for antibody delivery during passive immunotherapy.

Decreased Expression of KLF4 Leading to Functional Deficit in Pediatric Patients with Intestinal Failure and Potential Therapeutic Strategy Using Decanoic Acid.

Pediatric intestinal failure (IF) is the reduction in gut function to below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth. The overall goal in treating IF is to achieve intestinal adaptation; however, the underlying mechanisms have not been fully understood. In this study, by performing single-cell RNA sequencing in pediatric IF patients, we found that decreased Kruppel-Like Factor 4 (KLF4) may serve as the hub gene responsible for the functional deficit in mature enterocytes in IF patients, leading to the downregulation of solute carrier (SLC) family transporters (e.g., SLC7A9) and, consequently, nutrient malabsorption. We also found that inducible KLF4 was highly sensitive to the loss of certain enteral nutrients: in a rodent model of total parenteral nutrition mimicking the deprivation of enteral nutrition, the expression of KLF4 dramatically decreased only at the tip of the villus and not at the bottom of crypts. By using IF patient-derived intestinal organoids and Caco-2 cells as in vitro models, we demonstrated that the supplementation of decanoic acid (DA) could significantly induce the expression of KLF4 along with SLC6A4 and SLC7A9, suggesting that DA may function as a potential therapeutic strategy to promote cell maturation and functional improvement. In summary, this study provides new insights into the mechanism of intestinal adaptation depending on KLF4, and proposed potential strategies for nutritional management using DA.

Genome-wide identification and analysis of TCP family genes in Medicago sativa reveal their critical roles in Na+/K+ homeostasis

BackgroundMedicago sativa is the most important forage world widely, and is characterized by high quality and large biomass. While abiotic factors such as salt stress can negatively impact the growth and productivity of alfalfa. Maintaining Na+/K+ homeostasis in the cytoplasm helps reduce cell damage and nutritional deprivation, which increases a salt-tolerance of plant. Teosinte Branched1/ Cycloidea/ Proliferating cell factors (TCP) family genes, a group of plant-specific transcription factors (TFs), involved in regulating plant growth and development and abiotic stresses. Recent studies have shown TCPs control the Na+/K+ concentration of plants during salt stress. In order to improve alfalfa salt tolerance, it is important to identify alfalfa TCP genes and investigate if and how they regulate alfalfa Na+/K+ homeostasis.ResultsSeventy-one MsTCPs including 23 non-redundant TCP genes were identified in the database of alfalfa genome (C.V XinJiangDaYe), they were classified into class I PCF (37 members) and class II: CIN (28 members) and CYC/TB1 (9 members). Their distribution on chromosome were unequally. MsTCPs belonging to PCF were expressed specifically in different organs without regularity, which belonging to CIN class were mainly expressed in mature leaves. MsTCPs belongs to CYC/TB1 clade had the highest expression level at meristem. Cis-elements in the promoter of MsTCPs were also predicted, the results indicated that most of the MsTCPs will be induced by phytohormone and stress treatments, especially by ABA-related stimulus including salinity stress. We found 20 out of 23 MsTCPs were up-regulated in 200 mM NaCl treatment, and MsTCP3/14/15/18 were significantly induced by 10 μM KCl, a K+ deficiency treatment. Fourteen non-redundant MsTCPs contained miR319 target site, 11 of them were upregulated in MIM319 transgenic alfalfa, and among them four (MsTCP3/4/10A/B) genes were directly degraded by miR319. MIM319 transgene alfalfa plants showed a salt sensitive phenotype, which caused by a lower content of potassium in alfalfa at least partly. The expression of potassium transported related genes showed significantly higher expression in MIM319 plants. ConclusionsWe systematically analyzes the MsTCP gene family at a genome-wide level and reported that miR319-TCPs model played a function in K+ up-taking and/ or transportation especially in salt stress. The study provide valuable information for future study of TCP genes in alfalfa and supplies candidate genes for salt-tolerance alfalfa molecular-assisted breeding.

Inhibition of stress proteins TRIB3 and STC2 potentiates sorafenib sensitivity in hepatocellular carcinoma

Sorafenib resistance is one of the main obstacles to the treatment of advanced hepatocellular carcinoma (HCC). Stress proteins TRIB3 and STC2 confer cell resistance to a variety of stresses, including hypoxia, nutritional deprivation, and other perturbations, which induce endoplasmic reticulum stress. However, the role of TRIB3 and STC2 in sorafenib sensitivity to HCC remains unclear. In this study, our results indicated that the common differentially expressed genes (DEGs) in sorafenib-treated HCC cells obtained from the NCBI-GEO database (Huh7 and Hep3B cells; GSE96796) included TRIB3, STC2, HOXD1, C2orf82, ADM2, RRM2, and UNC93A. The most significantly upregulated DEGs were TRIB3 and STC2, which were both stress protein genes. Bioinformatic analysis in NCBI public databases indicated that TRIB3 and STC2 were highly expressed in HCC tissues and closely associated with poor prognoses in HCC patients. Further investigation showed that inhibition of TRIB3 or STC2 with siRNA could enhance the anti-cancer effect of sorafenib in HCC cell lines. In conclusion, our study showed that stress proteins TRIB3 and STC2 are closely associated with sorafenib resistance in HCC. The combination of TRIB3 or STC2 inhibition and sorafenib may be a promising therapeutic strategy for HCC.

Cellular Senescence in Intervertebral Disc Aging and Degeneration: Molecular Mechanisms and Potential Therapeutic Opportunities.

Closely associated with aging and age-related disorders, cellular senescence (CS) is the inability of cells to proliferate due to accumulated unrepaired cellular damage and irreversible cell cycle arrest. Senescent cells are characterized by their senescence-associated secretory phenotype that overproduces inflammatory and catabolic factors that hamper normal tissue homeostasis. Chronic accumulation of senescent cells is thought to be associated with intervertebral disc degeneration (IDD) in an aging population. This IDD is one of the largest age-dependent chronic disorders, often associated with neurological dysfunctions such as, low back pain, radiculopathy, and myelopathy. Senescent cells (SnCs) increase in number in the aged, degenerated discs, and have a causative role in driving age-related IDD. This review summarizes current evidence supporting the role of CS on onset and progression of age-related IDD. The discussion includes molecular pathways involved in CS such as p53-p21CIP1, p16INK4a, NF-κB, and MAPK, and the potential therapeutic value of targeting these pathways. We propose several mechanisms of CS in IDD including mechanical stress, oxidative stress, genotoxic stress, nutritional deprivation, and inflammatory stress. There are still large knowledge gaps in disc CS research, an understanding of which will provide opportunities to develop therapeutic interventions to treat age-related IDD.

A Novel Phenazine Analog, CPUL1, Suppresses Autophagic Flux and Proliferation in Hepatocellular Carcinoma: Insight from Integrated Transcriptomic and Metabolomic Analysis

CPUL1, a phenazine analog, has demonstrated potent antitumor properties against hepatocellular carcinoma (HCC) and indicates a promising prospect in pharmaceutical development. However, the underlying mechanisms remain largely obscure. Multiple HCC cell lines were used to investigate the in vitro effects of CPUL1. The antineoplastic properties of CPUL1 were assessed in vivo by establishing a xenograft nude mice model. After that, metabolomics, transcriptomics, and bioinformatics were integrated to elucidate the mechanisms underlying the therapeutic efficacy of CPUL1, highlighting an unanticipated involvement of autophagy dysregulation. CPUL1 suppressed HCC cell proliferation in vitro and in vivo, thereby endorsing the potential as a leading agent for HCC therapy. Integrative omics characterized a deteriorating scenario of metabolic debilitation with CPUL1, presenting an issue in the autophagy contribution of autophagy. Subsequent observations indicated that CPUL1 treatment could impede autophagic flow by suppressing autophagosome degradation rather than its formation, which supposedly exacerbated cellular damage triggered by metabolic impairment. Moreover, the observed late autophagosome degradation may be attributed to lysosome dysfunction, which is essential for the final stage of autophagy and cargo disposal. Our study comprehensively profiled the anti-hepatoma characteristics and molecular mechanisms of CPUL1, highlighting the implications of progressive metabolic failure. This could partially be ascribed to autophagy blockage, which supposedly conveyed nutritional deprivation and intensified cellular vulnerability to stress.

Protein-Deficient Pigs Cannot Maintain Reduced Glutathione Homeostasis When Subjected to the Stress of Inflammation

The mechanisms responsible for depletion of systemic glutathione levels in nutritional deprivation and/or in infective and inflammatory conditions have not been fully established. We quantified the effects of protein undernutrition and experimental inflammation on the concentration and synthesis of reduced glutathione in the erythrocytes, liver and jejunal mucosa of young pigs. Two groups of five piglets consumed diets containing either 23 or 3% protein and, after 4 wk, were infused intravenously with [13C2]glycine before and 48 h after subcutaneous injections of turpentine. Erythrocyte, hepatic and intestinal mucosal reduced glutathione was quantified as the monobromobimane derivative by HPLC. Reduced glutathione synthesis was determined by measurements of the tracer/tracee ratio of reduced glutathione-bound glycine. In well-nourished piglets, turpentine injection had no effect on erythrocyte reduced glutathione concentrations or rate of synthesis. Protein undernutrition was associated with lower erythrocyte reduced glutathione concentrations (1.05 ± 0.04 vs. 1.32 ± 0.06 mmol/L, P < 0.01) and synthesis (42 ± 5 vs. 60 ± 5%/d), and turpentine inflammation caused a further fall in erythrocyte reduced glutathione concentration to 0.96 ± 0.05 mmol/L, despite a significant (P < 0.05) increase in reduced glutathione synthesis. The combination of protein undernutrition and inflammation had a marked effect on mucosal reduced glutathione concentration (37 ± 3% of control) and synthesis (65 ± 5% of control). Hepatic reduced glutathione concentration and synthesis did not differ in the two groups. We conclude that the biosynthetic supply of reduced glutathione is sufficient to withstand an inflammatory challenge in well-nourished piglets but not in protein-deficient animals.

Tritrichomonas foetus Cell Division Involves DNA Endoreplication and Multiple Fissions.

Tritrichomonas foetus and Trichomonas vaginalis are extracellular flagellated parasites that inhabit animals and humans, respectively. Cell division is a crucial process in most living organisms that leads to the formation of 2 daughter cells from a single mother cell. It has been assumed that T. vaginalis and T. foetus modes of reproduction are exclusively by binary fission. However, here, we showed that multinuclearity is a phenomenon regularly observed in different T. foetus and T. vaginalis strains in standard culture conditions. Additionally, we revealed that nutritional depletion or nutritional deprivation led to different dormant phenotypes. Although multinucleated T. foetus are mostly observed during nutritional depletion, numerous cells with 1 larger nucleus have been observed under nutritional deprivation conditions. In both cases, when the standard culture media conditions are restored, the cytoplasm of these multinucleated cells separates, and numerous parasites are generated in a short period of time by the fission multiple. We also revealed that DNA endoreplication occurs both in large and multiple nuclei of parasites under nutritional deprivation and depletion conditions, suggesting an important function in stress nutritional situations. These results provide valuable data about the cell division process of these extracellular parasites. IMPORTANCE Nowadays, it's known that T. foetus and T. vaginalis generate daughter cells by binary fission. Here, we report that both parasites are also capable of dividing by multiple fission under stress conditions. We also demonstrated, for the first time, that T. foetus can increase its DNA content per parasite without concluding the cytokinesis process (endoreplication) under stress conditions, which represents an efficient strategy for subsequent fast multiplication when the context becomes favorable. Additionally, we revealed the existence of novel dormant forms of resistance (multinucleated or mononucleated polyploid parasites), different than the previously described pseudocysts, that are formed under stress conditions. Thus, it is necessary to evaluate the role of these structures in the parasites' transmission in the future.

Redox Regulation of Autophagy in Cancer: Mechanism, Prevention and Therapy.

Reactive oxygen species (ROS), products of normal cellular metabolism, play an important role in signal transduction. Autophagy is an intracellular degradation process in response to various stress conditions, such as nutritional deprivation, organelle damage and accumulation of abnormal proteins. ROS and autophagy both exhibit double-edged sword roles in the occurrence and development of cancer. Studies have shown that oxidative stress, as the converging point of these stimuli, is involved in the mechanical regulation of autophagy process. The regulation of ROS on autophagy can be roughly divided into indirect and direct methods. The indirect regulation of autophagy by ROS includes post-transcriptional and transcriptional modulation. ROS-mediated post-transcriptional regulation of autophagy includes the post-translational modifications and protein interactions of AMPK, Beclin 1, PI3K and other molecules, while transcriptional regulation mainly focuses on p62/Keap1/Nrf2 pathway. Notably, ROS can directly oxidize key autophagy proteins, such as ATG4 and p62, leading to the inhibition of autophagy pathway. In this review, we will elaborate the molecular mechanisms of redox regulation of autophagy in cancer, and discuss ROS- and autophagy-based therapeutic strategies for cancer treatment.

The long-term and intergenerational effects of early-life hunger experience on human capital and labor market outcomes

Using individual-level retrospective data on early-life hunger experience from China, we investigate the long-term effects of early nutritional deprivation on one's own and adult children's human capital and labor market outcomes. With an instrumental variable approach, we find that hunger experience lowers educational attainment and job quality of the first generation. But this negative impact on human capital does not transmit to the second generation, possibly due to parents' compensatory behavior of human capital investment and extra attention given to children. Our findings imply that the negative impact of non-extreme nutritional adversities on human capital and labor market outcomes are likely to decrease over generations.

Protein-caloric restriction induced HPA axis activation and altered the milk composition imprint metabolism of weaned rat offspring

ObjectivesMaternal protein-caloric restriction during lactation can malprogram offspring into having a lean phenotype associated with metabolic dysfunction in early life and adulthood. The aim of this study was to investigate the relationships between nutritional stress, maternal behavior and metabolism, milk composition, and offspring parameters. Additionally, we focused on the role of hypothalamus–pituitary–adrenal axis hyperactivation during lactation. MethodsDams were fed a low-protein diet (4% protein) during the first 2 wk of lactation or a normal-protein diet (20% protein) during all lactation. Analyses of dams, milk, and offspring were conducted on postnatal days (PD) 7, 14, and 21. ResultsBody weight and food intake decreased in dams, which was associated with reduced fat pad stores and increased corticosterone levels at PD 14. The stressed low-protein diet dams demonstrated alterations in behavior and offspring care. Despite nutritional deprivation, dams adapted their metabolism to provide adequate energy supply through milk; however, we demonstrated elevated corticosterone and total fat levels in milk at PD 14. Male offspring also showed increased corticosterone at PD 7, associated with a lean phenotype and alterations in white and brown adipose tissue morphology at PD 21. ConclusionExposure to protein-caloric restriction diet of dams during lactation increased the glucocorticoid levels in dams, milk, and offspring, which is associated with alterations in maternal behavior and milk composition. Thus, glucocorticoids and milk composition may play an important role in metabolic programming induced by maternal undernutrition.

COMPARITVE STUDY OF SMEAR LAYER REMOVAL AND ANTIBACTERIAL ACTIVITY OF SILVER, CHITOSAN NANOPARTICLES AND SODIUM HYPOCHLORITE AGAINST ENTEROFECALIS WHEN USED AS ROOT CANAL IRRIGANTS- IN VITRO STUDY

Background: As a very resistant microorganism in infected root canals, Enterococcus faecalis (E. faecalis) can stubbornly survive lethal challenges and invade dentinal tubules, making it the most persistent pathogen in root canal treatment. Enterococcus faecalis (E. faecalis) is the most commonly encountered microorganism detected in persistent root canal infections. These bacteria possess certain virulence factors, invade dentinal tubules and resist nutritional deprivation. Proper irrigation is an essential step for success in root canal therapies which is achieved by using excellent endodontic irrigants. Aim: To evaluate the antimicrobial efficacy of Sodium Hypochlorite (NaOCl), Silver Diamine Fluoride (SDF), Chitosan Nanoparticles (CNPs) root canal irrigants against the bacterial strain of Enterococcus Faecalis (E. faecalis) using agar well diffusion method. Materials and Methods: In this in-vitro study, the test materials were manipulated in accordance with the manufacturer’s instructions. The antimicrobial properties of root canal irrigants were evaluated by using agar diffusion method using bacterial strain of Enterococcus faecalis (ATCC 29212). 0.25 mL of each irrigant was placed on to 6.5 mm diameter blotting papers which were placed in 7 mm diameter wells on the Mueller Hinton agar plates. Later, E. faecalis strains were inoculated with sterile cotton swab on to the agar plates. Results: The p-value Sodium Hypochlorite showed the greatest zone of inhibition followed by SDF and Chitosan Nanoparticles respectively (p Sodium Hypochlorite showed the greatest zone of inhibition followed by SDF, Bioactive Glass Nanoparticles and Chitosan Nanoparticles respectively. Conclusion: Sodium Hypochlorite was the most effective root canal irrigant followed by SDF ,whereas Chitosan Nanoparticles was the least efficacious compared to the rest against Enterococcus Faecalis.

Labour markets, families and public policies shaping gender relations and parenting: Introduction to the Special Issue

Objective: This article introduces the reader to the Special Issue "Labour markets, families and public policies shaping gender relations and parenting" and gives a theoretical and empirical overview of gender roles and gender equality in Europe. Background: This Special Issue analyses the connection between labour markets, families, social policy, and gender relations in several European countries. Method: The six included articles are based on qualitative and quantitative approaches and data that have been gathered in Finland, Norway, Poland, Spain, and across the entire EU. Results: Key findings are: (1) In less egalitarian countries, children of single parents suffer more nutritional, educational and social life deprivation. (2) The institutional design of parental leave can contribute to reproducing gender inequality in the use of leave. (3) The institutional design interacts with cultural norms in shaping fatherhood practices of migrant fathers. (4) Individualised, performance-based wage and career schemes can counteract the effects of gender-equalising family policies. (5) Fathers taking leave independently from the mother and for an extended period are more involved in childcare beyond the leave period, and (6) the use of longer unpaid parental leave by mothers leads to a more unequal distribution of childcare between the parents. Conclusion: This Special Issue highlights that even in the most egalitarian countries, there remain persistent challenges to achieving gender equality regarding labour market, institutions and family life.

Do unwanted children face growth penalties in resource poor environments? Evidence from Roma Settlements in Serbia.

In a high fertility context, research on the relationship between parental investment, unwanted births and child nutritional outcomes is limited. The implications may be especially relevant for children coming from the most disadvantaged backgrounds and at increased risk of nutritional deprivation. This study assessed the association between maternal investment, unwanted births disaggregated into mistimed and unwanted children, and child nutritional outcomes in a poor population of Serbian Roma. Multiple Indicator Cluster Surveys rounds 5 and 6 data for Serbian Roma settlements were used to account for the association between two measures of maternal investment: weight at birth and parity, and mistimed and unwanted children, and children height-for-age z-score (HAZ), weight-for-age z score (WAZ) and weight-for- height z-score (WHZ). The sample included 130 children aged 0-24 months. The child variables were age, gender, and birth order, while maternal independent variables included age, literacy and access to improved toilet facility as proxies for socioeconomic status. Children born with low birth weight (lower maternal investment in utero) face a significant deficit in terms of their nutritional outcomes, measured by HAZ and WAZ. The effect was aggravated for height if the child was unwanted while there was a positive relationship between access to improved toilet facility and WHZ. Unwanted children were of higher birth order, with older, higher parity mothers than mistimed children. Many of the Roma children may be at risk of undernutrition, however, Roma children who received lower maternal investment in utero, unwanted and living in poorest households may face additional risk.

Nutrition regulates the expression of storage proteins in Bombyx mori via insulin-like/FoxO signaling pathway

Insect serum proteins, also termed storage proteins (SPs), are hexamer proteins that form amino acid reservoirs important for the development of pupae and embryos in most insects. In this study, we investigated the SP genes expression and regulation pathways in silkworms (Bombyx mori). We observed that B. mori SPs (BmSPs) in the fat body of larvae were strongly decreased by starvation, suggesting they respond to nutrition deprivation. Further, we examined the relationship between BmSP expression and the insulin-like signaling pathway (ILS) to study the regulation of BmSPs expression. The results showed that insulin up-regulated the expression of BmSPs, but an inhibitor of the ILS pathway protein PI3K downregulated the expression of BmSPs in B. mori larvae. Similar results were observed in cultured fat body in vitro and BmE cells. We then over-expressed FoxO, an ILS transcriptional factor, in BmE cells and B. mori larvae to further verify the regulatory role of ILS on expression of BmSPs and found BmFoxO negatively regulates the expression of BmSPs in both BmE cells and larvae. Moreover, BmFoxO was dephosphorylated and translocated from the cytoplasm to the nucleus under starvation treatment. Finally, an element on −2627–2644 bp upstream of the transcription start site of BmSP1 was identified as the binding site of BmFoxO by electrophoretic mobility shift assay and verified by chromatin immunoprecipitation. In summary, our results indicate that nutrient uptake triggers the expression of BmSPs via the ILS/FoxO signaling pathway. This study provides a reference for further study on the expression and regulation of insect SP genes.

Nutrition deprivation affects the cytotoxic effect of CD8 T cells in hepatocellular carcinoma

Nutrition deprivation affects the cytotoxic effect of CD8 T cells in hepatocellular carcinoma

Nutrition deprivation affects the cytotoxic effect of CD8 T cells in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the third leading cause of cancer-related death worldwide. Factors including carcinogens, infection of hepatitis viruses, alcohol abuse, and metabolic disorders such as non-alcoholic fatty liver disease mainly contribute to HCC initiation and progression. Immunotherapy is one of the most powerful tools for unresectable HCC treatment in patients. CD8+ T cells are a major immune component in the tumor microenvironment with cytotoxic effects against cancer cells. However, these CD8+ T cells commonly display an exhaustion phenotype with high expression of programmed cell death protein 1, T-cell immunoglobulin and mucin-domain containing-3, and/or lymphocyte-activation gene 3, producing low levels of perforin (PRF1) and granzyme B (GZMB), as well as anti-tumor cytokines, such as interferon gamma and tumor necrosis factor alpha. In the referenced study, the authors also showed that deprivation of glutamine decreased the antitumor function of CD8+ T cells, as well as the production of PRF1 and GZMB. However, the role of each amino acid in T cell function and exhaustion may depend on tumor type and tumor microenvironment, including the source of other nutrients. Overall, amino acids or other nutrient metabolites in the tumor microenvironment play a pivotal role in both tumor growth and immune response.