bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of Mitochondrial Folate Transporter Gene (Slc25A32) Induces Embryonic Lethality and Neural Tube Defects in Mice
Authors: Kim Jimi 
Published: November 2023

Neural tube defects (NTDs) are among the most common birth defects in humans. The causes of NTDs are thought to be multifactorial, including genetic, environmental, and nutritional factors. Multiple studies have shown that periconceptional supplementation with folic acid can reduce the incidence of NTDs. Despite more than 40 years of intensive effort, we still do not understand the mechanisms that underlie these folate‐dependent processes. Having a long‐standing interest in transport systems involved in one carbon metabolism, we developed a new mouse NTD model by knocking out the mitochondrial folate transporter MFT (Slc25A32) gene. MFT is an inner mitochondrial membrane protein that transports folates into mitochondria. In the inner mitochondrial membrane, MFT mediates the reversible transport of tetrahydrofolate (THF) between the cytosol and the mitochondrial matrix and plays a role in maintaining folate concentration within the cell.To examine the function of MFT during embryonic development, embryos had been dissected from heterozygous pregnant MFT+/− dams between E10.5‐E12.5. We analyzed the phenotypes of MFT knockout embryos from heterozygous MFT+/− breeding pairs. All nullizygous MFT−/−embryos exhibited 100% penetrant neural tube defects that were confined mostly to the head region and sometimes extending to the cervical or thoracic region. We determined that loss of a specific folate‐dependent transport protein leads to NTDs and this new mouse model provides insight to understand a folate‐specific transport mechanism of the MFT that underlie folate dependent process of NTD.Support or Funding InformationSupported in part by National Institutes of Health (NIH) grants HD067244, ES021006, and NS076465 to RHF.
The effects of glutamine‐ and n‐3 polyunsaturated fatty acids‐supplemented resuscitation fluid on circulating cytokines and neutrophil activity in rats with trauma‐hemorrhagic shock
Authors: Wu Yi‐Chen , Lo Hui‐Chen , Huang Fu‐Huan 
Published: November 2023

Hemorrhagic shock is an emergent condition usually caused by trauma, surgery, and parturition. Patients with hemorrhagic shock suffer from decreased energy and oxygen delivery and need immediate fluid resuscitation. However, extensive volume of resuscitation fluids may increase oxidative stress and activate inflammatory response. Studies showed that n‐3 polyunsaturated fatty acids (PUFAs) have anti‐inflammatory activity and glutamine is the main source of energy for immune cells. Therefore, the aim of the present study was to investigate the effects of n‐3 PUFA‐ and/or glutamine‐supplemented resuscitation fluids on systemic inflammation in rats with trauma‐hemorrhagic shock (THS). Male SD rats suffered with 5 cm laparotomy and catheterization in the left carotid artery and right jugular vein were divided into a sham‐operated group (SM group) and 5 THS groups. For the 5 THS groups, the blood was withdrawn from the left carotid artery to reach a mean arterial pressure 30 to 35 mmHg within 10 min for the induction of THS. After 60 minutes of hypovolemia, THS rats were resuscitated with shed blood and 3‐fold (LR group) or equal volume of lactate Ringer's solutions without (TH group) or with supplementation of L‐alanyl‐L‐glutamine (GN group), n‐3 PUFAs (FA group), or glutamine plus n‐3 PUFAs (GF group) within 10 minutes via right jugular vein. The SM, TH, GN, FA, and GF groups were further infused with continuous, low rate (~1.4 ml/h) of resuscitation fluids for 42 hours. Normal control rats with no surgery (NC group) were also included. The results showed that the TH group had significantly decreased circulating red blood cells, hemoglobin, hematocrit, serum albumin, and plasma myeloperoxidase (MPO) activity, a neutrophil produced enzyme, compared to the NC and SM groups. Compared to the SM group, the LR and TH groups had significantly increased plasma interleukin (IL)‐6 and relative liver weights, respectively. Serum blood urea nitrogen was significantly increased in the LR and TH groups and was further increased in the GN and GF groups. Compared to the TH group, the GN group had significantly increased serum glucose and decreased plasma interferon‐gamma; the FA group had significantly increased spleen weights and plasma MPO activity and decreased plasma interferon‐gamma; and the GF group had significantly decreased plasma IL‐4, IL‐6, tumor‐necrosis factor‐alpha, and interferon‐gamma. These results suggest that n‐3 PUFAs‐supplemented resuscitation fluids with or without glutamine may decrease circulating pro‐and anti‐inflammatory cytokines and increase systemic neutrophil activity in rats with THS.Support or Funding InformationNSC 102‐2320‐B‐030‐005‐MY3
Effects of Choline Deficiency on Composition of Sow's Milk
Authors: Mudd Austin T , Johnson Stacey K , Alexander Lindsey S , Getty Caitlyn M , Dilger Ryan N 
Published: November 2023

Choline is an essential micronutrient required for many biological functions including synthesis of phospholipids, proper neurodevelopment, and DNA methylation. Whereas choline is known to be expressed at high concentrations in early postpartum milk, little emphasis has been placed on how choline status affects maternal milk composition throughout lactation. As such, the objective of this study was to use the choline‐deficient sow model to assess the compositional changes of expressed milk throughout lactation and its impact on piglet growth. Up to 250 ml of milk was collected from 14 sows (n = 7 each on choline‐deficiency and choline‐adequate lactation diets) at each of 3 time‐points from farrowing to weaning: d 0 (colostrum), d 7–9 (mature milk), and d 17–19 (weaning). Colostrum was collected within 6 h of farrowing and 3‐day intervals were used for mature and weaning milk to ensure adequate and representative milk collection. To promote milk letdown, intramuscular injections of oxytocin were administered. Sow milk production and piglet growth were measured using the weigh‐suckle‐weigh procedure on piglet d of age 1, 8, and 18. Piglet bodyweight growth, measured at 2, 7, and 18 d of age, exhibited a main effect of day (P < 0.05); however no interaction (i.e., diet x day) or main effect of diet were observed. Proximate analysis of milk revealed a main effect of day (P < 0.05) for each of the following measures: dry matter, ash, crude protein, organic matter, gross energy, acid‐hydrolyzed fat, lactose, phosphorus, and calcium. Total free choline exhibited a main effect of day (P < 0.05) with choline concentrations decreasing from colostrum to mature and finally weaning milk; no interaction (i.e., diet x day) or main effect of diet were observed. Diet by day interactions were observed for phosphoethanolamine (P = 0.02), threonine (P = 0.01), asparagine (P = 0.04), and cystathionine/allocystathionine (P = 0.01). A main effect of diet was also observed for alpha‐amino‐n‐butyric acid (P = 0.04). In summary, perinatal choline status appears to affect nutrient composition of sow's milk, but these effects were not sufficient to cause differences in piglet growth during the pre‐weaning period.Support or Funding InformationSupport for this project provided by Mead Johnson Nutrition.
Newborn cardiac structural alterations in response to salt restriction or overload during pregnancy
Authors: Seravalli Priscila , Zago Breno Calazans , de Oliveira Ivone Braga , Veras Mariana Matera , Heimann Joel 
Published: November 2023

ObjectiveThis study aims to evaluate a possible influence of high‐ or low‐salt diet during pregnancy on heart structure in neonate males and females of Wistar rats.MethodsPregnant rats were fed with normal, high‐ or low‐salt diet (NR, HO and HR groups, respectively) from the first day of pregnancy until delivery. Hearts of the newborns (5–6/group) were collected in the first 24 hours of life. Total heart volume (stereology) and nuclear transversal diameter were evaluated.Results (mean±SEMtableConclusionAlterations in cardiac structure in male but not in female neonates are induced by high‐salt intake during pregnancy.Support or Funding InformationThis study was funded by FAPESP (2013/00458‐7)

HO
NR
HR
Statistical Analysis

Dams weight (g)

351±23*
377±36
386±42
* P<0.05 vs HR

Litter size (n)

14±0.8
14±0.6
14±0.5
NS

Newborns

Body Weight (g)
Male
6.4±0.09*
6.47±0.07
6.45±0.08
* P<0.05 vs NR e HR

Female
5.1±0.07*
6.1±0.09
6.0±0.08
* P<0.05 vs NR e HR

Heart weight (g)
Male
5.9±0.2
6.3±0.2
6.0±0.2
NS

Female
6.1±0.2
6.2±0.1
5.9±0.2
NS

Heart volume (mm3)
Male
2.6±0.14*
3.1±0.12
3.1 ±0.20
* P<0.05 vs NR

Female
2.4±0.10
3.0±0.36
2.8±0.20
NS

Left ventricle nuclear transversal diameter (μm)
Male
5.9±0.1S
5.7±0J21
6.6±0.15*
* P<0.05 vs NR

Female
5.9±0.23
5.5±0.23
6.1±0.25
NS

Right ventricle nuclear transversal diameter (μm)
Male
5.9±0.18
5.6±0.13
6.4±0.31*
* P<0.05 vs NR

Female
5.7±0.20
5.3±0.17
5.8±0.16
NS
A reduction of myeloperoxidase and interleukin‐10 expressions in mesenteric lymph nodes of the rats fed a cholic acid‐supplemented diet
Authors: JOE GA‐HYUN , Hori Shota , Shimizu Hidehisa , Hara Hiroshi , Ishizuka Satoshi 
Published: November 2023

BackgroundBile acids (BAs) are synthesized from cholesterol in hepatocytes and contribute to absorption of hydrophobic nutrients such as lipids and hydrophobic vitamins. Ingestion of high‐fat diet promotes BA secretion. Aging increases the ratio of cholic acid (CA) against chenodeoxycholic acid in the primary BAs. To mimic these conditions, we fed a diet supplemented CA and found attenuation of intestinal permeability, suggesting a possibility that immune system is involved in subsequent development of disorders. To investigate the effect of CA on immune functions, we analyzed gene expressions of immune responses in mesenteric lymph nodes of the CA‐fed rats.Material and methodWKAH/HkmSlc male rats (three weeks old) were fed an AIN‐93G‐based diet with or without a CA supplementation for 13 weeks. Also, BA metabolism was evaluated by using feces and some tissues. Mesenteric lymph nodes were collected at 13 weeks to analyze immune‐related gene expressions with PCR array and RT‐qPCR.ResultThe CA supplementation significantly decreased the myeloperoxidase (Mpo) and interleukin‐10 (Il10) expressions. Mpo is an enzyme found in neutrophils and monocytes that catalyze radical production and modulate macrophage functions. Il10 is one of the key cytokines to down‐regulate a variety of inflammatory responses and expressed in M2 macrophages. Also, CA‐ingestion had no effect on tumor necrosis factor and interleukin‐1β expressions known as pro‐inflammatory cytokines.ConclusionThe CA supplementation might modulate function of immune cells as well as neutrophils, macrophages and dendritic cells. Also, the decreases of Mpo and Il10 expressions can participate in disease developments observed in the CA‐fed rats.
Relationship Between Vitamin D Status and Plasma Aminothiol Redox in Critically Ill Children
Authors: Alvarez Jessica A , Grunwell Jocelyn R , Gillespie Scott E , Tangpricha Vin , Hebbar Kiran 
Published: November 2023

BackgroundCritically ill populations incur high levels of oxidative stress. Vitamin D deficiency, which is common in children presenting to the pediatric intensive care unit (PICU), has been shown to correlate with plasma aminothiol redox imbalance, as well as systemic inflammation. The purpose of this study was to investigate the relationship between vitamin D status and plasma markers of aminothiol redox and inflammation in critically ill children.MethodsThis was a cross‐sectional study of n = 50 PICU patients. Blood was drawn within 24 hr of admission to the PICU. Plasma glutathione (GSH), glutathione disulfide (GSSG), cystine (Cys), and cysteine (CySS) were measured with high‐performance liquid chromatography, and their associated redox potentials determined (EhGSSG and Eh CySS, respectively). Plasma 25‐hydroxyvitamin D [25(OH)D] was measured using a chemiluminescent assay. Vitamin D insufficiency was defined as 25(OH)D levels < 30 ng/mL. Plasma markers of inflammation were assayed with a multiplex platform and ELISA.ResultsMean age (± SD) was 11.8 ± 5.2 yrs, and 56% of patients were male. 74% of patients had vitamin D insufficiency.. Proportionally fewer patients in the vitamin D insufficient group required mechanical ventilation (p=0.009). Plasma Cys and CySS did not differ by vitamin D status, although Eh CySS was lower (more reduced; p−=0.005) in the vitamin D sufficient group. Plasma GSH and GSSG were lower in the vitamin D sufficient group (p=0.017 and 0.011, respectively), with a trend towards lower EhGSSG in the vitamin D insufficient group (p=0.076). Plasma glutamine levels were lower in the vitamin D sufficient group (p=0.005). Plasma LL‐37 was higher in the vitamin D sufficient group (p=0.025), although there were no differences in other markers of inflammation. Adjustment for age, sex, race, weight, and ventilation status attenuated the difference in plasma Eh CySS (p=0.08). In linear regression analyses, serum 25(OH)D was inversely associated with plasma Eh CySS p=0.006), although adjustment for age, sex, race, weight, and ventilation status attenuated the relationship (p=0.09).ConclusionIn critically ill children, vitamin D sufficiency was associated with less oxidized plasma EhCySS, the redox state of the primary extracellular redox couple (Cys and CySS), and with higher plasma LL‐37, an indicator of innate immune function. Lower plasma GSH, GSSG, and glutamine in vitamin D sufficient patients may suggest vitamin D‐regulated mechanisms to preserve extracellular and/or the intracellular redox states during critical illness, although further study is needed.Support or Funding InformationThis study was supported by the Children's Healthcare of Atlanta Friends (grant number 38234), the National Institutes of Health (UL1 TR000454 and K01 DK102851), the Emory+Children's Statistical Core, and the Emory+Children's Biomarkers Core.
Undernutrition, Nutrient Intake and Acute Phase Response of Anemic Children
Authors: Agdeppa Imelda Angeles , Capanzana Mario V 
Published: November 2023

BackgroundUndernutrition in the Philippines is alarmingly high and this increases the risk to infection.ObjectiveThis study aimed to assess the acute phase response, iron and physical growth and nutrient intake of anemic schoolchildren aged 6 to 9 years old.MethodsScreening for haemoglobin (hb) was done among 2423 children. The anemia rate was 10 % (246) with mean hb of 11.0 g/dl. Only 228 children were included in the analysis. All Mean age of children was 7.3 years. The average household size is 6 members. Mean monthly income tended to cluster around approximately P14,000.00 with an average daily food expenditure of P260.00 or U$5.5. Major occupation of breadwinner are production and service related. Weight and height were measured using standard techniques. Serum Ferritin (SF), transferrin receptors (TfR), C‐reactive protein (CRP) and α1 – acid glycoprotein (AGP) and retinol – binding proteins (RBP) were measured using sandwich ELISA method. The presence of infection is defined as values higher than the cut‐offs for CRP (>10mg/L) or AGP (>1g/L). Food intake was collected using 24h recall.ResultsAmong the anemic children, mean weight was 19.7 kg, mean height was 115.4 cm. Stunting prevalence among anemic children was 27.6 %, underweight 24.1 % and wasting 10.5 %. Mean levels SF was 69.2ug/L, TfR 6.9 mg/L and RBP 0.99 umol/L. Mean intakes of energy was 1325 kcal, protein 42.8g, carbohydrates 189.3g, fats 44.2g, iron 7.7mg, vitamin A 526 IU, and vitamin C 29.2 mg. Among anemic children, 15% are with infections of which 28.6% was underweight, stunted (25.7%), and wasted (20.0%). Among anemic children with infections the mean SF level was 94.5 ug/L, TfR 7.0 mg/L, and mean food intake was 1299 kcal. The presence of infection puts children to undernutrition by 20%.ConclusionAnemic children with high CRP or high AGP are more likely to be vitamin A deficient.RecommendationPolicies addressing reduction of malnutrition must integrate policies to reduce infection to improve health outcomes.
Serum retinol and selenium levels correlate negatively with hemolysis markers in sickle cell disease adult patients
Authors: Citelli Marta , Delesderrier Emília , Cordovil Karen , Omena Juliana , Santos‐Rodrigues Claudia Cople 
Published: November 2023

Sickle cell disease (SCD) is the most prevalent inherited hemoglobinopathy in the world. It is a hemolytic disease characterized by the presence of chronic inflammation and production of reactive species of oxygen and nitrogen. Very little is known about the adequate diet therapy for people with SCD, but it is seems that foods rich in antioxidants components should benefit these individuals. Thus, we hypothesized that insufficient quantities of selenium, retinol, alpha‐tocopherol and zinc could reduce the body's ability to regulate free radicals insults, leading to oxidative stress condition which could affect hemolysis in patients with SCD. We then conducted a study with 55 patients aged over 40 years and assessed the possible associations between serum levels of these nutrients and the indices of oxidative damage, inflammation and hemolysis markers. Reduced serum concentrations of retinol and selenium correlated negatively with hemolysis and inflammation markers values. In parallel, selenium and zinc were inversely correlated to to the concentrations of serum malondialdehyde. Therefore, our data point to the necessity for an adequate dietary intake of these nutrients.Support or Funding InformationBrasil Ministry of Health and FAPERJ
Synergistic effects of glutamine, citrulline, and antioxidant vitamin C and E on modulating splenocytic immune responses in rats with intestinal ischemia and reperfusion
Authors: Lo Hui‐Chen , Chiu Yu‐Wen , Lee Chien‐Hsing 
Published: November 2023

Intestinal ischemia and reperfusion (IIR) is a common event in patients with acute mesenteric ischemia, intestinal obstruction, organ transplantation, and hemorrhagic and septic shock. It has been demonstrated that IIR‐induced intestinal mucosa damage may cause systemic inflammation and multiple organ failure and further lead to death. Our previous study showed that oral glutamine/citrulline and antioxidant vitamins C/E have additive effects on attenuating intestinal damage and systemic inflammation in IIR rats. Herein, we investigated the effects of these supplements on IIR‐induced immune alterations. Male Wistar rats were divided into normal rats and IIR rats that underwent intestinal ischemia for 60 min and fed with placebo, glutamine/citrulline (AA), vitamins C/E (CE), or glutamine/citrulline plus vitamins C/E (AV) at 15 minutes before and 3, 9 and 21 hr after reperfusion. After 24 hr reperfusion, IIR‐increased plasma nitrate/nitrite was significantly reversed in rats with AA and CE and IIR‐increased interleukin‐6 was reversed in rats with AA, CE, and AV. The results of two‐way ANOVA showed that CE was a main factor to reverse IIR‐altered T‐helper leukocytes, B‐leukocytes, and monocytes and to increase tumor necrosis‐factor (TNF)‐alpha production in lipopolysaccharide‐stimulated leukocytes; and AA and CE were main factors to increase granulocytes in the circulation. In concanavalin A‐ and lipopolysaccharide‐stimulated splenocytes, AA was a main factor to increase TNF‐alpha and interleukin‐4 productions, CE was a main factor to increase interleukin‐4 productions, and AA and CE have significant interactions in TNF‐alpha and IL‐4 productions as shown in the significant increases in IIR rats with AV, not with AA or CE alone. In conclusion, oral glutamine/citrulline and vitamins C/E may have synergistic effects on modulating splenocytic immune responses in intestinal ischemia and reperfusion injury. The alleviated intestinal damage and systemic inflammation and the elevated splenocytic activity reveal that oral, combined administration of glutamine, citrulline, and antioxidant vitamins C and E may have beneficial effects in patients with intestinal ischemia and reperfusion.Support or Funding InformationNSC 98‐2320‐B‐030‐003‐MY3
Vitamin D attenuates MED28‐mediated cell growth and migration in human colon cancer cells
Authors: Hsieh Nien‐Tsu , Huang Chun‐Yin , Weng Yu‐Ting , Lee Ming‐Fen 
Published: November 2023

Increasing lines of evidence indicate that vitamin D can prevent cancer progression by reducing cell proliferation and increasing cell differentiation. MED28 is both a Mediator subunit for transcriptional activation and an interactor with Grb2, Src kinases, actin cytoskeleton, and merlin. Our laboratory previously reported that MED28 regulates cell growth and migration in human breast cancer cells, indicating a role of MED28 in cancer development. Recently we have also found that MED28 mediates Wnt/β‐catenin signaling in human colon cancer cells. This study was to investigate the effect of vitamin D on MED28 in colorectal cancer. Our data indicated that MED28 not only upregulated Wnt/β‐catenin signaling but also increased the expression of fibronectin, a mesenchymal marker, and reduced the expression of E‐cadherin, an epithelial marker, in human colon cancer cells. Moreover, MED28 suppressed the expression of microRNA‐22 (miR‐22) which has been shown involved in suppressing tumor growth, migration, and invasion in colorectal cancer cells. However, vitamin D reversed these MED28‐mediated effects by downregulating the expression of MED28 at both mRNA and protein levels. Taken together, vitamin D suppresses cell growth and migration, at least partially, by targeting MED28‐regulated miR‐22 and Wnt/β‐catenin signaling in colorectal cancer.Support or Funding InformationThis work was supported by the grant NSC102‐2320‐B‐309‐001‐MY3 to M‐F Lee.