Sensory factors may play an important role in the determination of appetite and food choices. Also, some adipokines may alter or predict the perception and pleasantness of specific odors. We aimed to ...analyze differences in smell-taste capacity between females with different weights and relate them with fat and fat-free mass, visceral fat, and several adipokines.
179 females with different weights (from low weight to morbid obesity) were studied. We analyzed the relation between fat, fat-free mass, visceral fat (indirectly estimated by bioelectrical impedance analysis with visceral fat rating (VFR)), leptin, adiponectin and visfatin. The smell and taste assessments were performed through the "Sniffin' Sticks" and "Taste Strips" respectively.
We found a lower score in the measurement of smell (TDI-score (Threshold, Discrimination and Identification)) in obese subjects. All the olfactory functions measured, such as threshold, discrimination, identification and the TDI-score, correlated negatively with age, body mass index (BMI), leptin, fat mass, fat-free mass and VFR. In a multiple linear regression model, VFR mainly predicted the TDI-score. With regard to the taste function measurements, the normal weight subjects showed a higher score of taste functions. However a tendency to decrease was observed in the groups with greater or lesser BMI. In a multiple linear regression model VFR and age mainly predicted the total taste scores.
We show for the first time that a reverse relationship exists between visceral fat and sensory signals, such as smell and taste, across a population with different body weight conditions.
Stress control as well as other psychological characteristics influence sports performance (SP) and could be relevant according to the playing position in team sports, such as the futsal where ...players have different specific functions within the team. The aim of this study was to analyze the psychological characteristics and profile related to SP of top-level young futsal players, according to the offensive or defensive role. A total of one hundred sixty-seven young promises futsal players participated in this study (84 U16 and 83 U19) and have been chosen to play Championship of Spain Selections. The Psychological Characteristics related to SP for soccer players Questionnaire was used, and one-way ANOVA test was performed based on the playing position (goalkeeper, defender and defender-wing, wing and wing-defender, pivot and wing-pivot, and universal). Results showed that goalkeepers had the best psychological profile and characteristics related to SP. Pivots and wing-pivots had less self-confidence, and universals players, less stress control in relation to the rest of the playing positions (p < 0.05). The main findings revealed that the psychological characteristics and profile related to SP in young promises futsal players are different according to the playing position, and this study suggest the inclusion of psychological-training programs in order to improve the psychological abilities of players, especially for players with offensive role who seek to score goals.
Although chemotherapy is the cornerstone treatment for patients with metastatic colorectal cancer (mCRC), acquired chemoresistance is common and constitutes the main reason for treatment failure. ...Monoclonal antibodies against insulin-like growth factor-1 receptor (IGF-1R) have been tested in pre-treated mCRC patients, but results have been largely deceiving.
We analysed time to progression, overall survival, and the mutational status of RAS, BRAF and nuclear p-IGF-1R expression by immunohistochemistry, in 470 metastatic CRC patients. The effect of IGF-1R activation and distribution was also assessed using cellular models of CRC and RNAi for functional validation.
Nuclear IGF-1R increased in metastatic tumours compared to paired untreated primary tumours, and significantly correlated with poor overall survival in mCRC patients. In vitro, chemo-resistant cell lines presented significantly higher levels of IGF-1R expression within the nuclear compartment, and PIAS3, a protein implicated also in the sumoylation process of intranuclear proteins, contributed to IGF-1R nuclear sequestration, highlighting the essential role of PIAS3 in this process. Intriguingly, we observed that ganitumab, an IGF-1R blocking-antibody used in several clinical trials, and dasatinib, an SRC inhibitor, increased the nuclear localisation of IGF-1R.
Our study demonstrates that IGF-1R nuclear location might lead to chemotherapy and targeted agent resistance.
Lack of vitamin D (VD) has been associated with colorectal cancer (CRC). VD has anti-inflammatory effects and regulates several cellular pathways by means of its receptor, including epigenetic ...modifications. Adipose tissue dysfunction has been related to low-grade inflammation, which is related to diseases like cancer. The aim of this study was to explore the relationship between serum 25-hydroxyvitamin D (25(OH)D), adipose tissue gene expression of VD receptor (VDR), pro-inflammatory markers, and the epigenetic factor DNA methyltransferase 3a (DNMT3A) as well as VDR promoter methylation in CRC.
Blood and visceral adipose tissue from 57 CRC and 50 healthy control subjects were collected. CRC subjects had lower serum 25(OH)D levels and higher VDR gene expression, and these were negatively correlated in the CRC group.
Adipose tissue
,
, and
gene expression were higher in the CRC subjects than in the control subjects. 25(OH)D correlated negatively with
and CRP. In turn, CRP correlated positively with
,
,
, and
gene expression as well as
that correlated positively with
and
.
mRNA was negatively correlated with serum 25(OH)D and positively correlated with
DNA methylation.
DNA methylation at position 4 had lower levels in the CRC group. Global
methylation at dinucleotide 3 was lower in the CRC group.
Our results suggest that adipose tissue may be a key factor in CRC development. The low 25(OH)D levels and high adipose tissue
expression in CRC may, at least in part, mediate this relationship by modifying adipose tissue DNA methylation and promoting inflammation.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by the intracellular lipid accumulation in hepatocytes. Excess caloric intake and high-fat diets are considered to ...significantly contribute to MASLD development.
To evaluate the hepatic and serum fatty acid (FA) composition in patients with different stages of MASLD, and their relationship with FA dietary intake and MASLD-related risk factors.
This was a case-control study in patients with obesity undergoing bariatric surgery at a University Hospital between January 2020 and December 2021. Participants were distributed in three groups: no MASLD (n = 26), steatotic liver disease (n = 33), and metabolic dysfunction-associated steatohepatitis (n = 32). Hepatic and serum FAs levels were determined by GC-MS. The nutritional status was evaluated using validated food frequency questionnaires. The hepatic expression of genes involved in FA metabolism was analyzed by RT-qPCR.
The hepatic, but not serum, FA profiles were significantly altered in patients with MASLD compared to those without MASLD. No differences were observed in FA intake between the groups. Levels of C16:0, C18:1, and the C18:1/C18:0 ratio were higher, while C18:0 levels and C18:0/C16:0 ratio were lower in patients with MASLD being significantly different between the three groups. Hepatic FA levels and ratios correlated with histopathological diagnosis and other MASLD-related parameters. The expression of genes involved in the FA metabolism was upregulated in patients with MASLD.
Alterations in hepatic FA levels in MASLD patients were due to an enhancement of the de novo lipogenesis in the liver.
Objective
Alterations in the hepatic lipidome are a crucial factor involved in the pathophysiology of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the serum and ...hepatic profile of branched‐chain fatty acids (BCFAs) in patients with different stages of NAFLD.
Methods
This was a case–control study performed in 27 patients without NAFLD, 49 patients with nonalcoholic fatty liver, and 17 patients with nonalcoholic steatohepatitis, defined by liver biopsies. Serum and hepatic levels of BCFAs were analyzed by gas chromatography–mass spectrometry. The hepatic expression of genes involved in the endogenous synthesis of BCFAs was analyzed by real‐time quantitative polymerase chain reaction (RT‐qPCR).
Results
A significant increase in hepatic BCFAs was found in subjects with NAFLD compared with those without NAFLD; no differences were observed in serum BCFAs between study groups. Trimethyl BCFAs, iso‐BCFAs, and anteiso‐BCFAs were increased in subjects with NAFLD (either nonalcoholic fatty liver or nonalcoholic steatohepatitis) compared with those without NAFLD. Correlation analysis showed a relationship between hepatic BCFAs and the histopathological diagnosis of NAFLD, as well as other histological and biochemical parameters related to this disease. Gene expression analysis in liver showed that the mRNA levels of BCAT1, BCAT2, and BCKDHA were upregulated in patients with NAFLD.
Conclusions
These results suggest that the increased production of liver BCFAs might be related to NAFLD development and progression.
It has been proposed that a mild form of acquired resistance to thyroid hormone may occur in the general population. Its clinical significance remains largely unknown. The objective of the study was ...to explore whether a newly described thyroid hormone resistance index is associated with the risk of mortality in a sample of community-dwelling euthyroid subjects representative of the adult population of Spain.
Longitudinal observational study including 3750 individuals, free of thyroid disease, TPO antibodies-negative (<50 IU/mL) and with TSH levels within the euthyroid range (≥0.5 and ≤5.0 mUI/mL) participating in the nationwide study Di@bet.es (2008-2010).
We used the Thyroid Feedback Quantile-based Index (TFQI) as a marker of resistance to thyroid hormone. The study population was grouped into categories according to their TFQI values at baseline. Fatal events were ascertained from the national death registry (end of follow-up December 2016).
A total of 231 deaths were recorded during an average follow-up of 7.3 years. Compared with the category with the highest sensitivity to free thyroxine (TFQI ≤ p5) (reference), the relative risk of mortality in the categories with TFQI > p5 and ≤p25; >p25 and ≤p50; >p50 and ≤p75; >p75 and ≤p95 and >p95 were 1.01, (0.47-2.19), 1.42 (0.68-2.97), 1.54 (0.74-3.22), 1.47 (0.70-3.11) and 2.61 (1.16-5.89), respectively (P for trend 0.003). The association remained significant after multivariate adjustment of the data (P for trend 0.017).
A thyroid hormone resistance index focused on deviations of the average pituitary response to thyroid hormones may be associated with all-cause mortality independently of other conventional risk factors and comorbidities.
Background
Inclusion body myositis (IBM) is an inflammatory myopathy clinically characterized by proximal and distal muscle weakness, with inflammatory infiltrates, rimmed vacuoles and mitochondrial ...changes in muscle histopathology. There is scarce knowledge on IBM aetiology, and non‐established biomarkers or effective treatments are available, partly due to the lack of validated disease models.
Methods
We have performed transcriptomics and functional validation of IBM muscle pathological hallmarks in fibroblasts from IBM patients (n = 14) and healthy controls (n = 12), paired by age and sex. The results comprise an mRNA‐seq, together with functional inflammatory, autophagy, mitochondrial and metabolic changes between patients and controls.
Results
Gene expression profile of IBM vs control fibroblasts revealed 778 differentially expressed genes (P‐value adj < 0.05) related to inflammation, mitochondria, cell cycle regulation and metabolism. Functionally, an increased inflammatory profile was observed in IBM fibroblasts with higher supernatant cytokine secretion (three‐fold increase). Autophagy was reduced considering basal protein mediators (18.4% reduced), time‐course autophagosome formation (LC3BII 39% reduced, P‐value < 0.05), and autophagosome microscopic evaluation. Mitochondria displayed reduced genetic content (by 33.9%, P‐value < 0.05) and function (30.2%‐decrease in respiration, 45.6%‐decline in enzymatic activity (P‐value < 0.001), 14.3%‐higher oxidative stress, 135.2%‐increased antioxidant defence (P‐value < 0.05), 11.6%‐reduced mitochondrial membrane potential (P‐value < 0.05) and 42.8%‐reduced mitochondrial elongation (P‐value < 0.05)). In accordance, at the metabolite level, organic acid showed a 1.8‐fold change increase, with conserved amino acid profile. Correlating to disease evolution, oxidative stress and inflammation emerge as potential markers of prognosis.
Conclusions
These findings confirm the presence of molecular disturbances in peripheral tissues from IBM patients and prompt patients' derived fibroblasts as a promising disease model, which may eventually be exported to other neuromuscular disorders. We additionally identify new molecular players in IBM associated with disease progression, setting the path to deepen in disease aetiology, in the identification of novel biomarkers or in the standardization of biomimetic platforms to assay new therapeutic strategies for preclinical studies.
Neuronal loss is the best neuropathological substrate that correlates with cortical atrophy and dementia in Alzheimer's disease (AD). Defective GABAergic neuronal functions may lead to cortical ...network hyperactivity and aberrant neuronal oscillations and in consequence, generate a detrimental alteration in memory processes. In this study, using immunohistochemical and stereological approaches, we report that the two major and non‐overlapping groups of inhibitory interneurons (SOM‐cells and PV‐cells) displayed distinct vulnerability in the perirhinal cortex of APP/PS1 mice and AD patients. SOM‐positive neurons were notably sensitive and exhibited a dramatic decrease in the perirhinal cortex of 6‐month‐old transgenic mice (57% and 61% in areas 36 and 35, respectively) and, most importantly, in AD patients (91% in Braak V–VI cases). In addition, this interneuron degenerative process seems to occur in parallel, and closely related, with the progression of the amyloid pathology. However, the population expressing PV was unaffected in APP/PS1 mice while in AD brains suffered a pronounced and significant loss (69%). As a key component of cortico‐hippocampal networks, the perirhinal cortex plays an important role in memory processes, especially in familiarity‐based memory recognition. Therefore, disrupted functional connectivity of this cortical region, as a result of the early SOM and PV neurodegeneration, might contribute to the altered brain rhythms and cognitive failures observed in the initial clinical phase of AD patients. Finally, these findings highlight the failure of amyloidogenic AD models to fully recapitulate the selective neuronal degeneration occurring in humans.
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