[Correlation of nutritional status with clinical characteristics and lung function in children with cystic fibrosis]. / å›Šæ€§çº¤ç»´åŒ–å„¿ç«¥è¥å »çŠ¶å†µä¸Žä¸´åºŠç‰¹å¾å’Œè‚ºåŠŸèƒ½çš„ç›¸å ³æ€§åˆ†æž.

OBJECTIVES: To investigate the nutritional status of children with cystic fibrosis (CF) and understand the correlation between malnutrition and clinical characteristics as well as lung function. METHODS: A retrospective analysis was performed on clinical data of CF children admitted from January 2016 to June 2023. Clinical characteristics of CF children with different nutritional statuses were compared, and the correlation between malnutrition and lung function was analyzed. RESULTS: A total of 52 CF children were included, comprising 25 boys (48%) and 27 girls (52%), aged between 7 months and 17 years. Respiratory symptoms were the predominant clinical manifestations (96%, 50/52). The prevalence of malnutrition was 65% (34/52), with moderate/severe malnutrition being the most common (65%, 22/34). The malnutrition group had a longer duration of illness, higher proportion of digestive system symptoms, and lower levels of serum albumin (P<0.05). Pulmonary function parameters, including forced expiratory volume in one second as a percentage of the predicted value, ratio of forced expiratory volume in one second to forced vital capacity, forced expiratory flow at 25% of forced vital capacity exhaled, forced expiratory flow at 50% of forced vital capacity exhaled, forced expiratory flow at 75% of forced vital capacity exhaled, and maximum mid-expiratory flow as a percentage of the predicted value, were lower in the malnutrition group compared to the normal nutrition group (P<0.05). Correlation analysis showed body mass index Z-score was positively correlated with the above six pulmonary function parameters (P<0.05). CONCLUSIONS: The prevalence of malnutrition is high in CF children and is associated with decreased lung function. CF children with higher body mass index have better lung function. Therefore, screening and evaluation of nutritional status as well as appropriate nutritional intervention should be emphasized in CF children.

Decreased vitamin D bio-availability with altered DNA methylation of its metabolism genes in association with the metabolic disorders among the school-aged children with degree I, II, and III obesity.

Obesity is strongly associated with disturbances of vitamin D (VD) metabolites in the animal models. However, the related epidemiological evidence is still controversial, especially the different degrees of obesity children. Hence, in this present representative case-control study, 106 obesity school-age children aged 7-12 years were included and divided into different subgroups as degree I (the age- and sex-specific BMI≥95th percentile, n=45), II (BMI ≥120% percentile, n=34) and III (BMI ≥140% percentile, n=27) obesity groups across the ranges of body mass index (BMI). While the age- and sex-matched subjects without obesity were as the control group. Notably, it was significantly different of body composition, anthropological and clinical characteristics among the above four subgroups with the dose-response relationships (P<.05). Moreover, comparing with the control group, the serum VD concentrations were higher, VD metabolites like 25(OH)D, 25(OH)D3 and 1,25(OH)2D, and related hydroxylases as CYP27A1, CYP2R1 and CYP27B1 were lower in the degree I, II, and III obesity subgroups (P<.05), which were more disorder with the anthropological and clinical characteristics as the obesity was worsen in a BMI-independent manner (P<.05). However, there was a significant increase of CYP27B1 in the degree III obesity group than those in the degree I and II obesity subgroups. Furthermore, the methylation patterns on the genome-wide (Methylation/Hydroxymethylation) and VD metabolism genes (CYP27A1, CYP2R1 and CYP27B1) were negatively correlated with the worse obesity and their related expressions (P<.05). In summary, these results indicated that obesity could affect the homeostasis of VD metabolism related genes such as CYP27A1, CYP2R1, CYP27B1 and etc through abnormal DNA methylation, resulting in the disorders of VD related metabolites to decrease VD bio-availability with the BMI-independent manner. In turn, the lower levels of VD metabolites would affect the liver function to exacerbate the progression of obesity, as the Degree II and III obesity subgroups.

Silencing of CPNE1-TRAF2 Axis Restrains the Development of Pancreatic Cancer.

BACKGROUND: Copine 1 (CPNE1) acts as a promoter in the progression of many kinds of cancers with the exception of pancreatic cancer (PC). This research is designed to probe the function of the CPNE1-tumor necrosis factor receptor-associated factor 2 (TRAF2) axis in PC. METHODS: In vivo and in vitro models of PC were constructed, and a series of biological function tests, including MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], colony formation, flow cytometry, and immunohistochemistry, were performed. RESULTS: The level of CPNE1 elevated dramatically in PC cells. Downregulation of CPNE1in PC cells resulted in the inhibition of colony formation and proliferation. In addition, the silencing of CPNE1 induced the G1/S arrest and apoptosis in PC cells. Additionally, TRAF2 positively interacted with CPNE1 in PANC cells. CPNE1 silencing also inhibited the growth of tumors in in vivo mouse models. Functional experiments revealed that the anti-tumor effect of CPNE1 silencing was counteracted by TRAF2 overexpression, and the tumor-promoting effect of TRAF2 overexpression was reversed by CPNE1 silencing. CONCLUSIONS: In summary, our findings indicate that the silencing of the CPNE1-TRAF2 axis restrains PC development.

A Novel Dual PI3K/mTOR Inhibitor, XIN-10, for the Treatment of Cancer.

An imbalance in PI3K/AKT/mTOR pathway signaling in humans often leads to cancer. Therefore, the investigation of anti-cancer medications that inhibit PI3K and mTOR has emerged as a significant area of research. The aim of this study was to explore the effect of XIN-10, a dual PI3K/mTOR inhibitor, on the growth as well as antiproliferation of tumor cells and to investigate the anti-tumor mechanism of XIN-10 by further exploration. We screened three cell lines for more in-depth exploration by MTT experiments. From the AO staining, cell cycle and apoptosis, we found that XIN-10 had a more obvious inhibitory effect on the MCF-7 breast cancer cell line and used this as a selection for more in-depth experiments. A series of in vitro and in vivo experiments showed that XIN-10 has superior antiproliferative activity compared with the positive drug GDC-0941. Meanwhile, through the results of protein blotting and PCR experiments, we concluded that XIN-10 can block the activation of the downstream pathway of mTOR by inhibiting the phosphorylation of AKT(S473) as well as having significant inhibitory effects on the gene exons of PI3K and mTOR. These results indicate that XIN-10 is a highly potent inhibitor with low toxicity and has a strong potential to be developed as a novel PI3Kα/mTOR dual inhibitor candidate for the treatment of positive breast cancer.

Cellular Id1 inhibits hepatitis B virus transcription by interacting with the novel covalently closed circular DNA-binding protein E2F4.

Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), which required developing novel therapies targeting the inhibition of HBV transcription and replication due to current limited treatment options. We explored novel target for the development of novel therapies targeting the inhibition of HBV replication and transcription. The expression of Id1 and E2F4 in HCC cells and tissues was detected by qRT-PCR and western blot. We investigated the Id1 and E2F4-mediated transcription of HBV infection by using HepG2.2.15, HepAD38, HepG2-NTCP cell lines and AAV/HBV-infected mice. Interactions between the two host proteins and viral covalently closed circular DNA (cccDNA) were assessed using subcellular localization, protein-protein interaction, chromatin immunoprecipitation, and luciferase assays. Ectopic Id1 significantly reduced HBV transcription and replication in both HBV-expressing cells and AAV/HBV-infected mice. Id1 and E2F4 could form a heterodimer to prevent E2F4 from promoting HBV transcription and replication. E2F4 could directly bind to cccDNA and activate the HBV core promoter in cell lines. Furthermore, in vitro binding experiments confirmed that the sequence 1758'-TTAAAGGTC-1766', which is highly conserved among HBV genotypes, is the target site of the E2F4 homodimer. The findings suggest that E2F4 function as novel cccDNA-binding protein to directly activate HBV transcription by binding to Cp promoter region. Our results highlight the ability that E2F4 represent a pan-potential therapeutic target against HBV transcription and provide more clues to better understand the life cycle of HBV.

E2F4 Promotes the Proliferation of Hepatocellular Carcinoma Cells through Upregulation of CDCA3.

Liver cancer, the second most commonly diagnosed cancer, is associated with high mortality rates. E2F4 is a member of the E2F transcription factor family. There are limited studies on the role of E2F4 in hepatocellular carcinoma (HCC). In this study, the expression of E2F4 in HCC tissue samples and cell lines was analyzed using quantitative real-time polymerase chain reaction. E2F4 expression positively correlated with tumor size in patients with HCC. Additionally, E2F4 expression was greater in HCC cells than in normal LO2 cells. Furthermore, overexpression of E2F4 significantly enhanced the proliferation, migration, and invasion of HCC cells. The results of a luciferase assay revealed that E2F4 upregulated the expression of CDCA3 by binding to its promoter region (1863'-ACGCGCGAGAATG-1875') and consequently promoted proliferation and cell cycle progression of HCC cells. Taken together, these results demonstrated that E2F4 might play a vital role in HCC progression and could serve as a potential biomarker for the diagnosis and as a therapeutic target of HCC.

Circular RNA circSP3 promotes hepatocellular carcinoma growth by sponging microRNA-198 and upregulating cyclin-dependent kinase 4.

As a new class of endogenous noncoding RNAs, circular RNAs (circRNAs), have been found to influence cell development and function by sponging microRNAs. MicroRNA (miR)-198 is downregulated in various cancers, including hepatocellular carcinoma (HCC). We therefore searched for dysregulated circRNAs that could sponge miR-198 in HCC. By analyzing relevant circRNA databases (circBase, TargetScan and CircInteractome), we found that the miR-198-binding circRNA hsa_circSP3 is upregulated in HCC. CircSP3 expression correlated negatively with miR-198 expression in HCC tissues. Dual luciferase reporter assays indicated that circSP3 bound to miR-198. CircSP3 overexpression in HCC cells induced expression of cyclin-dependent kinase 4, a target gene of miR-198. Silencing circSP3 inhibited HCC cell proliferation and migration by downregulating cyclin-dependent kinase 4, whereas inhibiting miR-198 reversed those effects. In vivo experiments confirmed that circSP3 promoted xenograft tumor growth. These data suggest that circSP3 may be a novel biomarker for HCC.

Volumetric cone-beam computed tomography evaluation and risk factor analysis of external apical root resorption with clear aligner therapy.

OBJECTIVES: To investigate the prevalence and severity of external apical root resorption (EARR) volumetrically with clear aligner therapy using cone-beam computed tomography (CBCT) as well as determine the possible risk factors and develop a prediction model for EARR. MATERIALS AND METHODS: In this retrospective study, 320 incisors from 40 Class II patients treated with aligners (Invisalign) were included in this study. CBCT images were obtained at pretreatment (T0) and posttreatment (T1). Root volume was calculated by three-dimensional reconstruction of CBCT images, and apical tooth movement was measured from superimposed CBCT images. Changes in root volume were compared using paired t-tests, and the relationship between root volume loss and potential risk factors was analyzed by multiple linear regression. RESULTS: All of the measured incisors showed root volume loss, with an average of 11.48 ± 6.70 mm3, and the prevalence of severe resorption was 0.625%. The prediction model for EARR included variables of posttreatment sagittal root position (SRP), extraction, tooth type, and apical intrusion and extrusion displacements, with an R2 of 0.51. Age, sex, duration, pretreatment SRP, attachment, advancement, and retraction movements were excluded from the model. CONCLUSIONS: Most incisors showed mild to moderate resorption during aligner treatment; only a minimal percentage showed severe resorption. Posttreatment SRP (which showed the highest association with EARR), extraction, tooth type, and apical intrusion and extrusion displacements were risk factors for EARR.

Predicted and actual outcome of anterior intrusion with Invisalign assessed with cone-beam computed tomography.

INTRODUCTION: The purpose of this study was to compare predicted anterior teeth intrusion measurements with the actual clinical intrusion measurements using cone-beam computed tomography. Understanding the precision of the software in anticipating changes may help practitioners predict the need for overcorrection. METHODS: Twenty-two patients, with a mean age of 23.74 years, who underwent Invisalign (Align Technology, Santa Clara, Calif) clear aligners treatment for both arches only after having completed treatment with an initial series of aligners were included in this study. The pretreatment and posttreatment cone-beam computed tomography scans after the initial series were acquired by a single orthodontist practitioner. ClinCheck measurements were recorded with Align Technology. The long axis of the anterior tooth intrusion movement was measured in 142 teeth. A comparison between the predicted and actual measurements of anterior intrusion of the teeth was performed, and the intraclass correlation coefficients showed an almost perfect agreement in the linear measurements. RESULTS: A statistically notable difference between the predicted and actual measurements of anterior intrusion. The predicted intrusion movement of the maxillary canines (P = 0.001), maxillary lateral incisors (P <0.0001), and maxillary central incisors (P <0.0001) significantly differed from the actual values. Similarly, the intrusion movement in the mandibular teeth seemed to be inaccurate, with significant differences in the mandibular canines (P <0.0001) and mandibular lateral and central incisors (P <0.0001). CONCLUSIONS: The mean precision of true anterior intrusion with Invisalign clear aligners was 51.19%, and the mean amount of correction was 48.81%. The use of other supplementary methods of anterior teeth intrusion may be helpful to reduce the rate of midcourse corrections and refinements.

Improving rehabilitation and quality of life after percutaneous transhepatic cholangiography drainage with a rapid rehabilitation model.

BACKGROUND: Percutaneous transhepatic cholangiography drainage (PTCD) effectively treats biliary obstruction. However, patients must maintain the drainage tube after hospital discharge, which may interfere with daily life and work, potentially causing psychological distress. Postoperative rehabilitation is crucial, and strengthened nursing interventions can shorten recovery time. AIM: The aim was to evaluate an inpatient model to shorten rehabilitation duration and improve quality of life after PTCD. METHODS: A total of 118 patients with malignant obstructive jaundice who were admitted to our hospital between May 2018 and January 2021 were included and divided into observational (with therapy) and control (no therapy) groups of 59 each. RESULTS: The observational group had fewer hospitalization days than the control group. The complication, the PTCD fixed-tube prolapse, and tube-related admission rates within 3 mo after PTCD were significantly lower in the observation group than in the control group (P < 0.05). The fatigue, pain, nausea, vomiting, pruritus, emaciation, and fever scores after PTCD decreased in both groups compared with the scores before PTCD (P < 0.05). The quality of life scores after the intervention were higher in the observation than in the control group (P < 0.05). CONCLUSION: The model promoted rehabilitation after PTCD, reduced post-PTCD complications, and the tube-related admissions in the 3 mo after the procedure, and improved the quality of life.

Alteration of gut microbiota affects expression of adiponectin and resistin through modifying DNA methylation in high-fat diet-induced obese mice.

BACKGROUND: Adiponectin and resistin are typically secreted by the adipose tissue and are abnormally expressed in obesity. However, the underlying influential factors and mechanisms are to be elucidated. It is well known that the expression of genes is regulated by epigenetics while gut microbiota participates in epigenetic processes through its metabolites such as folate, biotin, and short-chain fatty acids (SCFAs). Therefore, we supposed that alteration of gut microbiota might affect the transcriptional expression of adiponectin and resistin through epigenetic regulation in obesity. METHODS: C57BL/6J mice were fed either a high-fat diet (34.9% fat by wt., 60% kcal) or a normal-fat diet (4.3% fat by wt., 10% kcal) for 16 weeks, with ampicillin and neomycin delivered via drinking water to interfere with gut microbiota development. Fecal microbiota was analyzed by 16S rRNA high-throughput sequencing. The mRNA expression levels of genes were measured by real-time quantitative RT-PCR. SCFA contents in feces were examined using gas chromatography. RESULTS: Alteration of the gut microbiota induced by antibiotic use, characterized by a dramatic reduction of the phylum Firmicutes and Actinobacteria and an increase of Proteobacteria with reductions of genera including Lactobacillus, norank_f_Bacteroidales_S24-7_group, Alistipes, Desulfovibrio, Helicobacter, etc., and increases in Bacteroides, Enterobacter, Klebsiella, inhibited the body weight gain in mice fed the high-fat diet instead of the normal-fat diet. The mRNA expression of adiponectin and resistin was upregulated by antibiotic use in mice fed the high-fat diet, accompanied by increased expression of fat oxidation and thermogenesis-related genes (PPAR-α, Pgc-1α, and Atgl) in the fat and/or liver, whereas no change in the expression of adiponectin and resistin was found in mice fed the normal-fat diet. Furthermore, antibiotic use reduced DNA methylation fractions of the adiponectin and resistin promoters and downregulated the expression of DNA methyltransferase 1 and 3a (DNMT1 and DNMT3a) with the high-fat diet feeding. CONCLUSION: Alteration of gut microbiota induced by antibiotic use may affect the expression of adiponectin and resistin in mice fed the high-fat diet by modifying promoter DNA methylation, thus leading to increased fatty acid oxidation and less body weight gain.

Perceived air quality and cognitive performance decrease at moderately raised indoor temperatures even when clothed for comfort.

This study investigated whether adjusting clothing to remain in neutral thermal comfort at moderately elevated temperature is capable of avoiding negative effects on perceived acute subclinical health symptoms, comfort, and cognitive performance. Two temperatures were examined: 23°C and 27°C. Twelve subjects were able to remain thermally comfortable at both temperatures by adjusting their clothing. They rated the physical environment, their comfort, the intensity of acute subclinical health symptoms, and their mental load, and they performed a number of cognitive tasks. Their physiological reactions were monitored. Their performance of several tasks was significantly worse at 27°C, and they reported increased mental load at this temperature. Skin temperature and humidity and respiration rate were higher, while blood oxygen saturation (SpO2) and pNN50 were lower at this temperature, the latter indicating increased stress. It is inferred that the observed physiological responses were mainly responsible for the negative effects on performance, as the subjects did not indicate any increased intensity of acute subclinical health symptoms although perceived air quality was worse at the higher temperature. The present results suggest that moderately elevated temperatures should be avoided even if thermal comfort can be achieved, as it may lead to reduced performance.

The HBx and HBc of hepatitis B virus can influence Id1 and Id3 by reducing their transcription and stability.

Hepatitis B virus (HBV) infection is closely related with the occurrence and development of hepatocellular carcinoma (HCC), in which Hepatitis B virus x protein (HBx) and core protein (HBc) play crucial roles. Additionally, inhibitors of differentiation (Id) proteins exhibited significant correlation with liver cancer development. Here, we identified that HBV dramatically inhibited the expression of Id1 and Id3 in both protein and transcriptional levels for the first time, whereas there was little effect of the virus on Id2. Additionally, two HBV coded protein, HBc and HBx, could reduce the expression of Id1 and Id3 distinctly, whereas the other two viral proteins, HBs and HBp were unable to affect Id1 and Id3 proteins. Both the activity inhibitors and activators further confirmed that HBc inhibited the expression of Id1 and Id3 by BMP/Smad signaling pathway. HBx could interact with both Id1 and Id3 at residues 112-136 of HBx protein, and it could inhibit the two Id proteins by accelerating their degradation. This is the first report about HBc and HBx regulating Id1 and Id3, whereas the detailed mechanism associated with above needed further experiments to clarify.

The expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in the compression area during orthodontic relapse.

OBJECTIVE: This study investigated the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in the compression area during orthodontic relapse in rat molars. MATERIALS AND METHODS: Thirty Wistar rats (6 weeks old) underwent orthodontic tooth movement (OTM) of the left first maxillary molar for 21 days, followed by removal of the force device. The contralateral maxillary molar served as a control with no mechanical force stimuli. Animals were sacrificed at 0, 1, 3, 7, and 14 days of relapse after force withdrawal. Tooth relapse and alveolar bone parameters were measured using microcomputed tomography (micro-CT). Maxilla sections were obtained for haematoxylin and eosin (HE), immunohistochemical staining [EMMPRIN, nuclear factor kappa B ligand (RANKL) and vascular endothelial growth factor (VEGF)] and tartrate-resistant acid phosphatase (TRAP). Correlation analyses were then performed. RESULTS: After force removal, nearly 79.88% of the total relapse occurred within the initial 3 days. The number of osteoclasts clearly increased while the alveolar bone density decreased on the pressure side on Day 3 of relapse. Moreover, the EMMPRIN expression level significantly increased on Day 1, peaked up on Day 3 and decreased on Days 7 and 14. Statistically, a strong positive correlation was found between EMMRPIN expression and the osteoclast number and RANKL and VEGF expression. CONCLUSION: EMMPRIN was highly expressed on the pressure side during the orthodontic tooth relapse, which could be involved in osteoclastogenesis and alveolar bone resorption in association with RANKL and VEGF expression.

Effects of Twin Inclined Plane Device on Adaptation and Ultrastructure Variations in Condyle of Growing Rats.

OBJECTIVE: This study investigates the effects of using a twin inclined plane device (TIPD) on the remolding and ultrastructure variation of mandibular condyle in growing rats. MATERIALS AND METHODS: Forty-eight male Wistar rats (six weeks old, body weight of approximately 190-210 g) were divided into experimental group (wearing appliance, n = 32) and control group (no appliance, n = 16). Samples were collected on days 3, 14, 30, and 60. The immunohistochemical analysis for vascular endothelial growth factor (VEGF) and type II collagen was carried out. Tartrate-resistant acid phosphatase (TRAP) reaction was performed to evaluate the osteoclastic activity. Three-dimensional morphometric images were reconstructed for morphometric analysis by microcomputed tomography (micro-CT). The ultrastructure of the condylar surface was observed by scanning electron microscopy (SEM). RESULTS: The expression of VEGF significantly increased, while the expression of type II collagen decreased in the experimental group at days 30 and 60. Furthermore, the enhanced osteoclast activity was observed under the subchondral bone, which was highest at day 30, and decreased to the lowest at day 60 in the experimental group. In addition, adaptive subchondral bone remolding in the posterior part of the condyle was observed at day 60 in the experimental group, and the SEM revealed the ultrastructure variations after installation of the TIPD. However, these changes began to reverse after 30 days. CONCLUSION: Condylar tissue changes point to the osteoclastic activity in the posterior region of the condyle. These adaptive changes point to bone resorption in the posterior condyle. Type II collagen and VEGF contribute to the MCC remolding induced by the TIPD. The ultrastructural changes in the posterior condylar area in response to mechanical stresses are recoverable at the initial stage.

Elevated airflow can maintain sleep quality and thermal comfort of the elderly in a hot environment.

The effect of elevated airflow on sleep quality was investigated with 18 elderly. Three airflow conditions were set: ceiling fan/30°C/max.0.8 m/s and mean 0.7 m/s, task fan/30°C/max.0.8 m/s and mean 0.6 m/s, and thermally neutral /27°C/0.2 m/s. Sleep quality was evaluated objectively by analysis of electroencephalogram signals that were continuously monitored during the sleeping period. Urinary cortisol concentrations were analyzed to measure the activity of sympathetic nervous system. No significant difference in sleep quality, thermal comfort, or cortisol concentration was found between the ceiling fan and the neutral condition. The duration of total sleep time decreased by 35 minutes, the duration of REM sleep decreased by 15 minutes, and the cortisol concentration in the morning increased by 50 ng/mL in the task fan than the other two conditions. Compared with ceiling fan, less heat load was removed in the task fan condition, possibly due to the lower air speed. This study shows that even small heat load led to reduced sleep quality and overactive sympathetic nervous system of the elderly. By supplying an airflow of 0.8 m/s evenly over the human body, the elderly could maintain sleep quality and thermal comfort at an air temperature that was 3 K higher than the neutral temperature.

LC-MS guided identification of dimeric 2-(2-phenylethyl)chromones and sesquiterpene-2-(2-phenylethyl)chromone conjugates from agarwood of Aquilaria crassna and their cytotoxicity.

Four previously unreported dimeric 2-(2-phenylethyl)chromones (1-4a) and three unprecedented sesquiterpene-2-(2-phenylethyl)chromone conjugates (5-7), comprising a sesquiterpenoid and a 5,6,7,8-tetrahydroxy-2-(2-phenylethyl)-5,6,7,8 -tetrahydro-4H-chromone moiety, as well as three known dimeric 2-(2-phenylethyl)chromones (4b, 8a, 8b) were identified from agarwood originating from Aquilaria crassna in Cambodia by LC-MS guided separation. Their structures were elucidated by extensive NMR techniques, HRESIMS and CD. All compounds were evaluated for their cytotoxicity against four human cancer cell lines. Compounds 6, 7, 8a, 8b displayed a range of cytotoxic activities with IC50 values in the rang 10.93-49.0 µM.

Dietary ratios of n-6/n-3 polyunsaturated fatty acids during maternal pregnancy affect hippocampal neurogenesis and apoptosis in mouse offspring / Las ratios nutricionales de ácidos grasos poliinsaturados n-6/n-3 durante la gestación afectan a la neurogénesis hipocampal y a la apoptosis en las crías de ratones

Objective: although n-3 polyunsaturated fatty acids (PUFAs) play crucial roles in brain development and function, neither the optimal level of n-3 PUFAs nor the optimal ratio of n-6/n-3 PUFAs in the maternal diet are well defined. In this study, we investigated the effects of dietary n-6/n-3 PUFA ratios during pregnancy on neurogenesis and apoptosis in the brains of mouse offspring. Metods: female C57BL/6J mice were fed one of three diets with high, medium and low ratios of n-6/n-3 PUFAs (15.7:1, 6.3:1, 1.6:1), as well as a high fish oil diet with a n-6/n-3 ratio of 1:5.7; an n-3 PUFA-deficient diet served as control. The feeding regimens began two months before mouse conception and continued for the duration of the pregnancy. The neurogenesis and apoptosis of hippocampal CA3 area in the offspring were detected. Results: compared to the n-3 PUFA-deficient diet, n-3 PUFA-containing diets, particularly those with n-6/n-3 PUFA ratios of 6.3:1 and 1.6:1, significantly increased both phosphorylation of histone H3 at ser 10 (p-H3ser10) and calretinin-positive cells in hippocampus CA3 of the offspring. Furthermore, increased expression of Bcl2 protein, decreased expression of Bax protein, and reduced caspase 3 activity and numbers of TUNEL apoptotic cells were found in the three diets with high, medium and low n-6/n-3 PUFA ratios. However, there were no differences in any of these parameters between the high fish oil diet group and the n-3 PUFA-deficient diet group. Conclusions: these data suggest that a higher intake of n-3 PUFAs with a lower ratio of n-6/n-3 PUFAs of between about 6:1 to 1:1, supplied to mothers during pregnancy, may benefit brain neurogenesis and apoptosis in offspring. However, excessive maternal intake of n-3 PUFAs may exert a negative influence on brain development in the offspring (AU)

Objetivo: a pesar de que los ácidos grasos poliinsaturados n-3 (PUFAs por sus siglas en inglés) desempeñan un papel fundamental en el desarrollo y en las funciones cerebrales, aún no está bien definido el nivel óptimo de PUFAs n-3 ni la ratio óptima de PUFA n-6/n-3 en la dieta materna. En este estudio hemos investigado los efectos de las ratios nutricionales de PUFA n-6/n-3 durante la gestación sobre la neurogénesis y la apoptosis en el cerebro de crías de ratón. Métodos: se alimentó a hembras de ratón C57BL/6J con una de las tres dietas de estudio: ratio alta, media y baja de PUFA n-6/n-3 (15,7:1, 6,3:1, 1,6:1). También se añadió una dieta rica en aceite de pescado con una ratio n-6/n-3 de 1:5,7; como control se empleó una dieta deficitaria en PUFA n-3. Los regímenes alimenticios se iniciaron dos meses antes de la concepción de los ratones y continuó durante todo el embarazo. Se detectó la neurogénesis y apoptosis del área hipocampal CA3 en las crías. Resultados: en comparación con la dieta deficitaria en PUFA n-3, las dietas con PUFA que contienen n-3, particularmente aquellas con ratios PUFA n-6/n-3 de 6,3:1 y 1,6:1, aumentaron significativamente la fosforilación de histona H3 en la Ser10 (p-H3ser10) y las células calretinina positivas en el área hipocampal CA3 de las crías. Además, se detectó un aumento de la expresión de proteí- na Bcl2, una reducción de la expresión de proteína Bax, y una reducción de la actividad de caspasa 3, así como de las cifras de células apoptósicas TUNEL en las tres dietas, con ratios altas, medias y bajas de PUFA n-6/n-3. Sin embargo, no se observó diferencias en ninguno de estos parámetros entre el grupo de dieta rica en aceite de pescado y el grupo de dieta deficitaria en PUFA n-3. Conclusiones: estos datos sugieren que una ingesta más elevada de PUFA n-3 con una ratio más baja de PUFAs n-6/n-3 entre 6:1 y 1:1 aproximadamente, administrada a las madres durante la gestación, podría ser beneficiosa para la neurogénesis cerebral y la apoptosis de las crías. Sin embargo, una ingesta excesiva de PUFA n-3 puede ejercer una influencia negativa sobre el desarrollo de las crías (AU)