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Maria L. Dentici Vittorio Maglione Emanuele Agolini Gino Catena Rossella Capolino Valentina Lanari Antonio Novelli Lorenzo Sinibaldi Davide Vecchio Michaela V. Gonfiantini Marina Macchiaiolo Maria C. Digilio Bruno Dallapiccola Andrea Bartuli 《American journal of medical genetics. Part A》2020,182(8):1977-1984
The tubulinopathies refer to a wide range of brain malformations caused by mutations in one of the seven genes encoding different tubulin's isotypes. The β‐tubulin isotype III (TUBB3) gene has a primary function in nervous system development and axon generation and maintenance, due to its neuron‐specific expression pattern. A recurrent heterozygous mutation, c.1228G > A; p.E410K, in TUBB3 gene is responsible of a rare disorder clinically characterized by congenital fibrosis of the extraocular muscle type 3 (CFEOM3), intellectual disability and a wide range of neurological and endocrine abnormalities. Other mutations have been described spanning the entire gene and genotype–phenotype correlations have been proposed. We report on a 3‐year‐old boy in whom clinical exome sequencing allowed to identify a de novo TUBB3 E410K mutation as the molecular cause underlying a complex phenotype characterized by a severe bilateral palpebral ptosis refractory to eye surgery, psychomotor delay, absent speech, hypogonadism, celiac disease, and cyclic vomiting. Brain MRI revealed thinning of the corpus callosum with no evidence of malformation cortical dysplasia. We reviewed available records of patients with TUBB3 E410K mutation and compared their phenotype with the clinical outcome of patients with other mutations in TUBB3 gene. The present study confirms that TUBB3 E410K results in a clinically recognizable phenotype, unassociated to the distinct cortical dysplasia caused by other mutations in the same gene. Early molecular characterization of TUBB3 E410K syndrome is critical for targeted genetic counseling and prompt prospective care in term of neurological, ophthalmological, endocrine, and gastrointestinal follow‐up. 相似文献
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Burova L Thern A Pigarevsky P Gladilina M Seliverstova V Gavrilova E Nagornev V Schalén C Totolian A 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2003,111(10):955-962
Our previous studies have indicated that the IgG-binding M-family proteins (IgGBP) of group A streptococci may be involved in eliciting experimental acute poststreptococcal glomerulonephritis (APSGN) in the rabbit. These surface proteins were also found to trigger production of anti-IgG, which might conceivably act to enhance renal deposition of immune complexes (IC). In the present study, a clinical isolate of serotype M22 (strain AL168), an isogenic double mutant deficient for both the IgGBPs Mrp and Emm, as well as mutants deficient in only one of the proteins were tested for capacity to induce glomerulonephritis. Streptococci to be used for injecting rabbits were heat-killed. Surface-bound IgG was removed by 1 M KSCN and cells were then repeatedly washed in PBS before use. Rabbits were injected intravenously with 109 cells three times a week for 8 weeks and, following one month of rest, for another 6 weeks. Deposits of IgG and C3 as well as induced chemokines TNF-alpha, IL-1beta and IL-6 were traced in cryostat sections using specific antibodies and appropriate peroxidase-labelled anti-antibodies. In four rabbits immunized with the double mutant strain, no deposits were found, and as examined by TEM, only subtle and transient renal changes were observed. In contrast, the original strain AL168 induced pronounced inflammatory and degenerative glomerular changes in all four rabbits injected, and deposits of TNF-alpha, IL-1beta and IL-6 were found in mesangial and endothelial cells. Similar deposits and glomerular changes were seen in all eight rabbits injected with the mrp-emm+ mutant and in four out of seven animals receiving the mrp+emm- mutant. There was a highly significant correlation between high levels of circulating anti-IgG and development of APSGN. These results confirm an important role of streptococcal IgGBP in triggering experimental APSGN as earlier proposed by our group. 相似文献
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Davide Serrano Chiara Pozzi Silvia Guglietta Bruno Fosso Mariano Suppa Patrizia Gnagnarella Federica Corso Federica Bellerba Debora Macis Valentina Aristarco Paolo Manghi Nicola Segata Cristina Trovato Maria Giulia Zampino Marinella Marzano Bernardo Bonanni Maria Rescigno Sara Gandini 《Nutrients》2021,13(2)
Obesity and diet are associated with colorectal cancer (CRC) risk, and microbiome could mediate this risk factor. To investigate this interaction, we performed a case–control study (34 CRC cases and 32 controls) and analyzed fecal microbiota composition using 16S rRNA metabarcoding and sub-sequential shotgun analyses of genomic bacterial DNA to evaluate the role of microbiome and diet in CRC etiology, taking into account vitamin D and other risk biomarkers. Dietary habits were evaluated using a short questionnaire. Multivariate methods for data integration and mediation analysis models were used to investigate causal relationships. CRC cases were significantly more often deficient in vitamin D than controls (p = 0.04); FokI and CYP24A1 polymorphism frequency were different between cases and controls (p = 0.03 and p = 0.02, respectively). A diet poor in fatty fish and rich in carbohydrates was found to be significantly associated with CRC risk (p = 0.011). The mediation analysis confirmed the significant role of the microbiome in mediating CRC risk—increasing levels of Bifidobacteria/Escherichia genera ratio, an indicator of “healthy” intestinal microbiome, can overcome the effect of diet on CRC risk (p = 0.03). This study suggests that microbiome mediates the diet effect on CRC risk, and that vitamin D, markers of inflammation, and adipokines are other factors to consider in order to achieve a better knowledge of the whole carcinogenic process. 相似文献
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Claudia Tonini Marco Segatto Francesca Martino Luisa Cigliano Martina Nazzaro Laura Barberio Maurizio Mandal Valentina Pallottini 《Nutrients》2021,13(1)
Background: A major problem of aging is the disruption of metabolic homeostasis. This is particularly relevant in the brain where it provokes neurodegeneration. Caloric restriction is a physiologic intervention known to delay the deleterious consequences of aging in several species ranging from yeast to mammals. To date, most studies on experimental models have started this dietary intervention from weaning, which is very difficult to be translated to human beings. Here, we study the effects of a more realistic dietary regimen in rats, starting at an advanced age and lasting for six months. Methods: we analyzed in the cortex and hippocampus, the proteins involved in the energetic balance of the cells, cholesterol metabolism, oxidative stress response, inflammation, synaptic impairment, and brain trophism. Results: our results suggest that caloric restriction in late life can revert only some age-related changes studied here. 相似文献
17.
Gabriele Piuri Monica Zocchi Matteo Della Porta Valentina Ficara Michele Manoni Gian Vincenzo Zuccotti Luciano Pinotti Jeanette A. Maier Roberta Cazzola 《Nutrients》2021,13(2)
Magnesium (Mg2+) deficiency is probably the most underestimated electrolyte imbalance in Western countries. It is frequent in obese patients, subjects with type-2 diabetes and metabolic syndrome, both in adulthood and in childhood. This narrative review aims to offer insights into the pathophysiological mechanisms linking Mg2+ deficiency with obesity and the risk of developing metabolic syndrome and type 2 diabetes. Literature highlights critical issues about the treatment of Mg2+ deficiency, such as the lack of a clear definition of Mg2+ nutritional status, the use of different Mg2+ salts and dosage and the different duration of the Mg2+ supplementation. Despite the lack of agreement, an appropriate dietary pattern, including the right intake of Mg2+, improves metabolic syndrome by reducing blood pressure, hyperglycemia, and hypertriglyceridemia. This occurs through the modulation of gene expression and proteomic profile as well as through a positive influence on the composition of the intestinal microbiota and the metabolism of vitamins B1 and D. 相似文献
18.
Milica Zrnic Ciric Miodrag Ostojic Ivana Baralic Jelena Kotur-Stevuljevic Brizita I. Djordjevic Stana Markovic Stefan Zivkovic Ivan Stankovic 《Nutrients》2021,13(3)
Dietary supplementation with sugar cane derivates may modulate low-density lipoprotein cholesterol (LDL-C) and proprotein convertase subtilisin/kexin type 9 (PCSK9) levels. The purpose of this study was to determine if dietary supplement (DS), containing Octacosanol (20 mg) and vitamin K2 (45 µg), could restore the disrupted physiologic relation between LDL-C and serum PCSK9. Double-blind, randomized, placebo-controlled, single-center study including 87 patients on chronic atorvastatin therapy was conducted. Eighty-seven patients were randomized to receive DS (n = 42) or placebo (n = 45), and followed for 13 weeks. Serum PCSK9 levels, lipid parameters and their relationship were the main efficacy endpoints. The absolute levels of PCSK9 and LDL-C were not significantly different from baseline to 13 weeks. However, physiologic correlation between % change of PCSK9 and % change of LDL-C levels was normalized only in the group of patients treated with DS (r = 0.409, p = 0.012). This study shows that DS can restore statin disrupted physiologic positive correlation between PCSK9 and LDL-C. Elevated PCSK9 level is an independent risk factor so controlling its rise by statins may be important in prevention of cardiovascular events. 相似文献
19.
Humberto Pea-Jorquera Valentina Campos-Núez Kabir P. Sadarangani Gerson Ferrari Carlos Jorquera-Aguilera Carlos Cristi-Montero 《Nutrients》2021,13(4)
This study aimed to determine whether pupils who have breakfast just before a cognitive demand, do not regularly skip breakfast, and consume a high-quality breakfast present higher cognitive performance than those who do not; furthermore, to establish differences according to their nutritional status. In this study, 1181 Chilean adolescents aged 10–14 years participated. A global cognitive score was computed through eight tasks, and the body mass index z-score (BMIz) was calculated using a growth reference for school-aged adolescents. The characteristics of breakfast were self-reported. Analyses of covariance were performed to determine differences in cognitive performance according to BMIz groups adjusted to sex, peak height velocity, physical fitness global score, and their schools. A positive association was found in adolescents’ cognitive performance when they had breakfast just before cognitive tasks, did not regularly skip breakfast, presented at least two breakfast quality components, and included dairy products. No significant differences were found between breakfast components, including cereal/bread and fruits/fruit juice. Finally, pupils who were overweight/obese who declared that they skipped breakfast regularly presented a lower cognitive performance than their normal-BMIz peers. These findings suggest that adolescents who have breakfast just prior to a cognitive demand and regularly have a high quality breakfast have better cognitive performance than those who do not. Educative nutritional strategies should be prioritized, especially in “breakfast skippers” adolescents living with overweight/obesity. 相似文献
20.
Silvio Buscemi Carola Buscemi Davide Corleo Giovanni De Pergola Rosalia Caldarella Francesco Meli Cristiana Randazzo Salvatore Milazzo Anna Maria Barile Giuseppe Rosafio Valentina Settipani Sabina Gurrera Antonio Maria Borzì Marcello Ciaccio 《Nutrients》2021,13(6)
Background: Vitamin D plays a pivotal role in calcium and phosphorus metabolism, also influencing bone tissue. Several studies have reported that vitamin D blood levels were significantly lower in people with obesity, probably due to its uptake by the adipose tissue. Clinical studies that investigated the changes of circulating levels of vitamin D following weight loss reported controversial data. A very low-calorie ketogenic diet is acknowledged as a reliable treatment to achieve a rapid weight loss. Therefore, we investigated the effect of weight loss, consequent to a very low-calorie ketogenic diet, on vitamin D blood concentrations. Methods: A cohort of 31 people with obesity underwent a very low-calorie ketogenic diet for 10–12 weeks. The serum concentrations of vitamin D, parathormone, calcium and phosphorous were measured before and after weight loss; they were compared to a control group of 20 non-obese, non-diabetic, age- and gender-matched persons. Results: Patients with obesity had a higher habitual intake of vitamin D than the control group (p < 0.05). However, the vitamin D blood levels of the obese group were significantly lower than those of the control group (p < 0.005) and they increased after weight loss (p < 0.001). At baseline, vitamin D blood concentrations of the persons with obesity were significantly correlated with both fat mass–kg (r = −0.40; p < 0.05) and body mass index (r = −0.47; p < 0.01). Following very low-calorie ketogenic diet, the change in vitamin D serum concentrations was correlated only with the change in fat mass–kg (r = −0.43; p < 0.01). Conclusion: This study confirmed that patients with obesity have lower vitamin D levels that normalize after significant weight loss, supporting the hypothesis that vitamin D is stored in the adipose tissue and released following weight loss. 相似文献