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Aging Cell Jul 2021Hematopoietic stem cells (HSCs) reside in a quiescent niche to reserve their capacity of self-renewal. Upon hematopoietic injuries, HSCs enter the cell cycle and...
Hematopoietic stem cells (HSCs) reside in a quiescent niche to reserve their capacity of self-renewal. Upon hematopoietic injuries, HSCs enter the cell cycle and encounter protein homeostasis problems caused by accumulation of misfolded proteins. However, the mechanism by which protein homeostasis influences HSC function and maintenance remains poorly understood. Here, we show that C/EBP homologous protein (CHOP), demonstrated previously to induces cell death upon unfolded protein response (UPR), plays an important role in HSCs regeneration. CHOP mice showed normal hematopoietic stem and progenitor cell frequencies in steady state. However, when treated with 5-FU, CHOP deficiency resulted in higher survival rates, associated with an increased number of HSCs and reduced level of apoptosis. In serial competitive transplantation experiments, CHOP HSCs showed a dramatic enhancement of repopulation ability and a reduction of protein aggresomes. Mechanistically, CHOP deletion causes reduced ATF3 expression and further leads to decreased protein aggregation and ROS. In addition, CHOP HSCs exhibited an increased resistance to IR-induced DNA damage and improved HSCs homeostasis and function in telomere dysfunctional (G3Terc ) mice. In summary, these findings disclose a new role of CHOP in the regulation of the HSCs function and homeostasis through reducing ATF3 and ROS signaling.
Topics: Activating Transcription Factor 3; Animals; Apoptosis; CCAAT-Enhancer-Binding Proteins; Cell Differentiation; Hematopoietic Stem Cells; Mice; Protein Deficiency; Reactive Oxygen Species
PubMed: 34128315
DOI: 10.1111/acel.13382 -
Nefrologia : Publicacion Oficial de La... 2014The presence of malnutrition in chronic kidney disease (CKD) is well-known. The discovery in the last 15 years of pathophysiological mechanisms that lead to this... (Review)
Review
The presence of malnutrition in chronic kidney disease (CKD) is well-known. The discovery in the last 15 years of pathophysiological mechanisms that lead to this process, such as anorexia, the increase of protein catabolism and inflammation, has created the need for a new name by the International Society of Renal Nutrition and Metabolism (ISRNM): protein-energy wasting syndrome (PEW). This document’s objectives are to propose the use of the term "desgaste proteico energético" (DPE) as a more accurate translation of the English term and to update the pathogenic mechanisms involved that are inherent to DPE (PEW). We simultaneously review the latest epidemiological evidence that highlight the relevance of malnutrition and its impact both on mortality and morbidity in CKD. Finally, we point out the need to redefine DPE (PEW) diagnostic criteria so that they are applicable to the Spanish population with CKD. We do not think that the criteria established by the ISRNM can be extrapolated to different populations, as is the case, for example, with interracial anthropometric differences.
Topics: Humans; Nutritional Status; Prevalence; Protein-Energy Malnutrition; Renal Insufficiency, Chronic; Terminology as Topic; Wasting Syndrome
PubMed: 25036065
DOI: 10.3265/Nefrologia.pre2014.Apr.12522 -
International Journal of Experimental... Apr 2021In a large part of the population inefficient ingestion of proteins, whether for cultural, aesthetic or economic reasons, is a global concern. Low-protein diets can...
In a large part of the population inefficient ingestion of proteins, whether for cultural, aesthetic or economic reasons, is a global concern. Low-protein diets can cause severe functional complications, mainly during the development and maturation of organs and systems, including the female reproductive system. The present study investigated the effect of nutritional protein restriction during puberty on the oestrous cycle and expression of sex steroid receptors (AR, ERα e ERβ) in ovarian and uterine tissues of adult rats. Protein restriction promoted lower body weight gain, feed efficiency and higher caloric intake. There was an increase in the oestrus phase arrest without changing the total length of the oestrous cycle. The consumption of low-protein diet also reduced the thickness of the uterine endometrium (uterine epithelium and endometrial stroma) in addition to increasing the number of primary and atretic follicles in the ovaries. Furthermore, the low-protein diet reduced the levels of androgen receptor (AR) and increased the oestrogen receptor β (ERβ) in the ovary, while no significant changes were observed in the uterus. Our study reinforces the importance of adequate protein intake during puberty, since physiological changes in this developmental period interfere with the histomorphometry of the ovaries and uteri, possibly resulting in impaired folliculogenesis and fertility in the reproductive period.
Topics: Animals; Estrous Cycle; Female; Ovary; Protein Deficiency; Rats; Rats, Inbred F344; Sexual Maturation; Uterus
PubMed: 33729619
DOI: 10.1111/iep.12388 -
International Journal For Parasitology Jan 2018Maternal dietary protein deficiency and gastrointestinal nematode infection during early pregnancy have negative impacts on both maternal placental gene expression and...
Maternal dietary protein deficiency and gastrointestinal nematode infection during early pregnancy have negative impacts on both maternal placental gene expression and fetal growth in the mouse. Here we used next-generation RNA sequencing to test our hypothesis that maternal protein deficiency and/or nematode infection also alter the expression of genes in the developing fetal brain. Outbred pregnant CD1 mice were used in a 2×2 design with two levels of dietary protein (24% versus 6%) and two levels of infection (repeated sham versus Heligmosomoides bakeri beginning at gestation day 5). Pregnant dams were euthanized on gestation day 18 to harvest the whole fetal brain. Four fetal brains from each treatment group were analyzed using RNA Hi-Seq sequencing and the differential expression of genes was determined by the edgeR package using NetworkAnalyst. In response to maternal H. bakeri infection, 96 genes (88 up-regulated and eight down-regulated) were differentially expressed in the fetal brain. Differentially expressed genes were involved in metabolic processes, developmental processes and the immune system according to the PANTHER classification system. Among the important biological functions identified, several up-regulated genes have known neurological functions including neuro-development (Gdf15, Ing4), neural differentiation (miRNA let-7), synaptic plasticity (via suppression of NF-κβ), neuro-inflammation (S100A8, S100A9) and glucose metabolism (Tnnt1, Atf3). However, in response to maternal protein deficiency, brain-specific serine protease (Prss22) was the only up-regulated gene and only one gene (Dynlt1a) responded to the interaction of maternal nematode infection and protein deficiency. In conclusion, maternal exposure to GI nematode infection from day 5 to 18 of pregnancy may influence developmental programming of the fetal brain.
Topics: Animals; Brain; Carrier Proteins; Female; Fetal Development; Fetal Diseases; Growth Differentiation Factor 15; Male; Maternal Inheritance; Mice; MicroRNAs; Pregnancy; Pregnancy Complications; Protein Deficiency; Trichostrongyloidea; Trichostrongyloidiasis; Troponin T; Tumor Suppressor Proteins
PubMed: 28903026
DOI: 10.1016/j.ijpara.2017.07.005 -
Haematologica May 2020Highly conserved among species and expressed in various types of cells, numerous roles have been attributed to the cellular prion protein (PrPC). In hematopoiesis, PrPC...
Highly conserved among species and expressed in various types of cells, numerous roles have been attributed to the cellular prion protein (PrPC). In hematopoiesis, PrPC regulates hematopoietic stem cell self-renewal but the mechanisms involved in this regulation are unknown. Here we show that PrPC regulates hematopoietic stem cell number during aging and their determination towards myeloid progenitors. Furthermore, PrPC protects myeloid progenitors against the cytotoxic effects of total body irradiation. This radioprotective effect was associated with increased cellular prion mRNA level and with stimulation of the DNA repair activity of the Apurinic/pyrimidinic endonuclease 1, a key enzyme of the base excision repair pathway. Altogether, these results show a previously unappreciated role of PrPC in adult hematopoiesis, and indicate that PrPC-mediated stimulation of BER activity might protect hematopoietic progenitors from the cytotoxic effects of total body irradiation.
Topics: Hematopoietic Stem Cells; Humans; Myeloid Progenitor Cells; Prion Proteins; Prions; Protein Deficiency
PubMed: 31371412
DOI: 10.3324/haematol.2018.205716 -
Gut Mar 1977The relationship between iron deficiency and protein deficiency and infestation of the rat with the nematode Nippostrongylus brasiliensis was investigated. There was a...
The relationship between iron deficiency and protein deficiency and infestation of the rat with the nematode Nippostrongylus brasiliensis was investigated. There was a significant delay in the expulsion of N. brasiliensis from the small intestine of both iron deficient and protein deficient animals and those with a combined deficiency of iron and protein. Iron repletion returned the time of worm expulsion to normal and this would appear to be related to iron deficiency per se rather than to anaemia. Antibody initiated damage to worms was normal in the control animals and in animals with nutritional deficiencies. This suggests that the defect in worm expulsion occurs either in the cell-mediated immune system or in one of the other mediators of expulsion. Extrapolation to the human situation has important therapeutic implications in that iron and protein deficiency may play an important role in the perpetuation of helminth infestations. Thus, to be successful antihelminth therapy should be accompanied by iron and protein supplementation.
Topics: Ancylostomatoidea; Animals; Hookworm Infections; Immunity, Cellular; Intestine, Small; Iron Deficiencies; Nippostrongylus; Protein Deficiency; Rats; Time Factors
PubMed: 558135
DOI: 10.1136/gut.18.3.182 -
The Journal of Nutrition Jan 2013Neonatal immune development begins in pregnancy and continues into lactation and may be affected by maternal diet. We investigated the possibility that maternal protein...
Neonatal immune development begins in pregnancy and continues into lactation and may be affected by maternal diet. We investigated the possibility that maternal protein deficiency (PD) during a chronic gastrointestinal (GI) nematode infection could impair neonatal immune development. Beginning on d 14 of pregnancy, mice were fed protein-sufficient (PS; 24%) or protein-deficient (PD; 6%) isoenergetic diets and were infected weekly with either 0 (sham) or 100 Heligmosomoides bakeri larvae. Pups were killed on d 2, 7, 14, and d 21 and dams on d 20 of lactation. Lymphoid organs were weighed. Cytokine concentration in maternal and pup serum and in milk from pup stomachs and lymphoid cell populations in pup spleen and thymus were determined using luminex and flow cytometry, respectively. GI nematode infection increased Th2 cytokines (IL-4, IL-5, IL-13), IL-2, IL-10, and eotaxin in serum of dams whereas PD reduced IL-4 and IL-13. The lower IL-13 in PD dams was associated with increased fecal egg output and worm burdens. Maternal PD increased vascular endothelial growth factor in pup milk and eotaxin in pup serum. Maternal infection increased eotaxin in pup serum. Evidence of impaired neonatal immune development included reduced lymphoid organ mass in pups associated with both maternal infection and PD and increased percentage of T cells and T:B cell ratio in the spleen associated with maternal PD. Findings suggest that increases in specific proinflammatory cytokines as a result of the combination of infection and dietary PD in dams can impair splenic immune development in offspring.
Topics: Animals; Animals, Newborn; Animals, Outbred Strains; Cytokines; Feces; Female; Gastrointestinal Diseases; Heligmosomatoidea; Immune System Diseases; Lactation; Lymphocyte Subsets; Lymphoid Tissue; Male; Maternal Nutritional Physiological Phenomena; Mice; Milk; Nematode Infections; Parasite Load; Pregnancy; Pregnancy Complications, Parasitic; Protein Deficiency; Random Allocation
PubMed: 23190758
DOI: 10.3945/jn.112.160457 -
Dietary Protein Intake and Transition between Frailty States in Octogenarians Living in New Zealand.Nutrients Aug 2021Adequate nutritional status may influence progression to frailty. The purpose of this study is to determine the prevalence of frailty and examine the relationship... (Comparative Study)
Comparative Study
Adequate nutritional status may influence progression to frailty. The purpose of this study is to determine the prevalence of frailty and examine the relationship between dietary protein intake and the transition between frailty states and mortality in advanced age. We used data from a longitudinal cohort study of Māori (80-90 years) and non-Māori (85 years). Dietary assessments (24-h multiple pass dietary recalls) were completed at the second year of follow-up (wave 2 and forms the baseline in this study). Frailty was defined using the Fried Frailty criteria. Multi-state modelling examined the association of protein intake and transitions between frailty states and death over four years. Over three quarters of participants were pre-frail or frail at baseline (62% and 16%, respectively). Those who were frail had a higher co-morbidity ( < 0.05), where frailty state changed, 44% showed a worsening of frailty status (robust → pre-frail or pre-frail → frail). Those with higher protein intake (g/kg body weight/day) were less likely to transition from robust to pre-frail [Hazard Ratio (95% Confidence Interval): 0.28 (0.08-0.91)] but also from pre-frail to robust [0.24 (0.06-0.93)]. Increased protein intake was associated with lower risk of transitioning from pre-frailty to death [0.19 (0.04-0.80)], and this association was moderated by energy intake [0.22 (0.03-1.71)]. Higher protein intake in this sample of octogenarians was associated with both better and worse outcomes.
Topics: Age Factors; Aged, 80 and over; Aging; Comorbidity; Dietary Proteins; Female; Frail Elderly; Frailty; Geriatric Assessment; Humans; Male; Native Hawaiian or Other Pacific Islander; New Zealand; Nutrition Assessment; Nutritional Status; Prevalence; Protein Deficiency; Recommended Dietary Allowances; Risk Assessment; Risk Factors
PubMed: 34445004
DOI: 10.3390/nu13082843 -
Lakartidningen May 2018There is a widespread myth that we have to be careful about what we eat so that we do not cause protein deficiency. We know today that it is virtually impossible to...
There is a widespread myth that we have to be careful about what we eat so that we do not cause protein deficiency. We know today that it is virtually impossible to design a calorie-sufficient diet, whether it is based on meat, fish, eggs, various vegetarian diets or even unprocessed whole natural plant foods, which is lacking in protein and any of the amino acids. The body is capable of taking incomplete proteins and making them complete by utilizing the amino acid recycling mechanism. The majority of amino acids absorbed from the intestinal tract are derived from recycled body protein. Research shows that high levels of animal protein intake may significantly increase the risk of premature mortality from all causes, among them cardiovascular diseases, cancer and type 2 diabetes.
Topics: Animals; Diet; Diet, High-Protein; Diet, Vegan; Fishes; Humans; Nutrition Policy; Protein Deficiency
PubMed: 29786804
DOI: No ID Found -
BMC Public Health Feb 2024Nutritional deficiencies remain serious medical and public health issues worldwide, especially in children. This study aims to analyze cross-country inequality in four...
BACKGROUND
Nutritional deficiencies remain serious medical and public health issues worldwide, especially in children. This study aims to analyze cross-country inequality in four common nutritional deficiencies (protein-energy malnutrition, dietary iron deficiency, vitamin A deficiency and iodine deficiency) among children from 1990 to 2019 based on Global Burden of Disease (GBD) 2019 data.
METHODS
Prevalence and disability-adjusted life years (DALYs) data as measures of four nutritional deficiency burdens in people aged 0 to 14 years were extracted from the GBD Results Tool. We analyzed temporal trends in prevalence by calculating the average annual percent change (AAPC) and quantified cross-country inequalities in disease burden using the slope index.
RESULTS
Globally, the age-standardized prevalence rates of dietary iron deficiency, vitamin A deficiency and iodine deficiency decreased, with AAPCs of -0.14 (-0.15 to -0.12), -2.77 (-2.96 to -2.58), and -2.17 (-2.3 to -2.03) from 1999 to 2019, respectively. Significant reductions in socio-demographic index (SDI)-related inequality occurred in protein-energy malnutrition and vitamin A deficiency, while the health inequality for dietary iron deficiency and iodine deficiency remained basically unchanged. The age-standardized prevalence and DALY rates of the four nutritional deficiencies decreased as the SDI and healthcare access and quality index increased.
CONCLUSIONS
The global burden of nutritional deficiency has decreased since 1990, but cross-country health inequalities still exist. More efficient public health measures are needed to reduce disease burdens, particularly in low-SDI countries/territories.
Topics: Child; Humans; Global Burden of Disease; Quality-Adjusted Life Years; Protein-Energy Malnutrition; Vitamin A Deficiency; Health Status Disparities; Iron, Dietary; Malnutrition; Health Inequities; Iron Deficiencies; Iodine; Global Health
PubMed: 38360585
DOI: 10.1186/s12889-024-17942-y