Miracle-dz/UniFAR-FTUs huggingface dataset:
Gliosis of astrocytes cultivated on coral skeleton is regulated by the matrix surface topography

Astrogilosis is the response of astrocytes to brain trauma which manifest opposite roles on brain injury repair. On the one hand, astrocytes undergoing astrogliosis inhibit tissue regeneration by forming scar tissue, but, on the other hand, they enhance damage repair through secretion of neuro-protecting and neurotrophic factors. Therefore, identifying means that regulate astrogliosis can provide a control over progression and repair of brain damage. We have previously shown that the calcium carbonate skeleton of corals upregulates two manifestations of astrogliosis in astrocytes in culture—expression of the Glial Fibrillay Acidic Protein (GFAP), and shape conversion from non-spiky to reactive spiky cell morphology. Here, we investigated if the surface topography of the coralline skeleton plays a role in GFAP expression and the morphogenesis of reactive astrocytes. To address that, we utilized the non-porous exoskeleton of the coral Trachyphyllia geoffroyi, having three topographies of distinct heights on its surface: rough surface (made of <30 μm height bumps), protrusions (50–250 μm) and ridges (>250 μm). We observed that astrocytes reacted similarly to all three structures in terms of adhesion, acquisition of a spiky morphology and organization in networks. By contrast, the extent by which these cells expressed GFAP was structure-dependent. The expression was 2-fold higher on protrusions and ridges than on the rough surface and acquired. Accordingly, the distribution pattern of the GFAP overexpressing astrocytes followed that of the protrusions and ridges. Hence, fabricating coralline scaffolds with designed flatness/protrusions/ridges ratios can serve to control astrogliosis-derived regeneration in TBI wounds, and as a result improve the capacity to repair brain damage.
Hemodynamic Stimulation Using the Biomimetic Cardiac Tissue Model (BCTM) Enhances Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) hold great promise for cardiovascular disease modeling and regenerative medicine. However, these cells are both structurally and functionally immature, primarily due to their differentiation into cardiomyocytes occurring under static culture which only reproduces biomolecular cues and ignores the dynamic hemodynamic cues that shape early and late heart development during cardiogenesis. To evaluate the effects of hemodynamic stimuli on hiPSC-CM maturation, we used the biomimetic cardiac tissue model to reproduce the hemodynamics and pressure/volume changes associated with heart development. Following 7 days of gradually increasing stimulation, we show that hemodynamic loading results in (a) enhanced alignment of the cells and extracellular matrix, (b) significant increases in genes associated with physiological hypertrophy, (c) noticeable changes in sarcomeric organization and potential changes to cellular metabolism, and (d) a significant increase in fractional shortening, suggestive of a positive force frequency response. These findings suggest that culture of hiPSC-CMs under conditions that accurately reproduce hemodynamic cues results in structural organization and molecular signaling consistent with organ growth and functional maturation.
Potassium channels in vascular smooth muscle: a pathophysiological and pharmacological perspective

Potassium (K+) ion channel activity is an important determinant of vascular tone by regulating cell membrane potential (MP). Activation of K+ channels leads to membrane hyperpolarization and subsequently vasodilatation, while inhibition of the channels causes membrane depolarization and then vasoconstriction. So far five distinct types of K+ channels have been identified in vascular smooth muscle cells (VSMCs): Ca+2‐activated K+ channels (BKCa), voltage‐dependent K+ channels (KV), ATP‐sensitive K+ channels (KATP), inward rectifier K+ channels (Kir), and tandem two‐pore K+ channels (K2P). The activity and expression of vascular K+ channels are changed during major vascular diseases such as hypertension, pulmonary hypertension, hypercholesterolemia, atherosclerosis, and diabetes mellitus. The defective function of K+ channels is commonly associated with impaired vascular responses and is likely to become as a result of changes in K+ channels during vascular diseases. Increased K+ channel function and expression may also help to compensate for increased abnormal vascular tone. There are many pharmacological and genotypic studies which were carried out on the subtypes of K+ channels expressed in variable amounts in different vascular beds. Modulation of K+ channel activity by molecular approaches and selective drug development may be a novel treatment modality for vascular dysfunction in the future. This review presents the basic properties, physiological functions, pathophysiological, and pharmacological roles of the five major classes of K+ channels that have been determined in VSMCs.
The prevalence of awake bruxism and sleep bruxism in the Dutch adult population

Summary Background Awake bruxism and sleep bruxism are common conditions amongst adult populations, although prevalence data are scarce. Objective This study aimed to assess the prevalence of awake bruxism and sleep bruxism in the Dutch adult population. Methods As part of a large epidemiologic survey on oral health of the general Dutch adult population, a total of 1209 subjects were asked about their bruxism behaviour during the day and during their sleep. The collected data were subjected to stratified analysis by five age groups (25‐34, 35‐44, 45‐54, 55‐64 and 65‐74 years), socioeconomic status, and gender. Results A prevalence of 5.0% of the total population was found for awake bruxism and of 16.5% for sleep bruxism. Regarding the five age groups, prevalence of 6.5%, 7.8%, 4.0%, 3.2% and 3.0%, respectively, were found for awake bruxism, and of 20.0%, 21.0%, 16.5%, 14.5% and 8.3%, respectively, for sleep bruxism. Women reported both awake bruxism and sleep bruxism more often than men. These differences were statistically significant. Concerning socioeconomic status (SES), both awake bruxism and sleep bruxism were more often found in high SES groups, being statistically significant for awake bruxism only. Conclusion Sleep bruxism is a common condition in the Dutch adult population, while awake bruxism is rarer.
Ghrelin Upregulates Oncogenic Aurora A to Promote Renal Cell Carcinoma Invasion

Ghrelin is a peptide hormone, originally identified from the stomach, that functions as an endogenous ligand of the growth hormone secretagogue receptor (GHSR) and promotes growth hormone (GH) release and food intake. Increasing reports point out ghrelin’s role in cancer progression. We previously characterized ghrelin’s prognostic significance in the clear cell subtype of renal cell carcinoma (ccRCC), and its pro-metastatic ability via Snail-dependent cell migration. However, ghrelin’s activity in promoting cell invasion remains obscure. In this study, an Ingenuity Pathway Analysis (IPA)-based investigation of differentially expressed genes in Cancer Cell Line Encyclopedia (CCLE) dataset indicated the potential association of Aurora A with ghrelin in ccRCC metastasis. In addition, a significant correlation between ghrelin and Aurora A expression level in 15 ccRCC cell line was confirmed by variant probes. ccRCC patients with high ghrelin and Aurora A status were clinically associated with poor outcome. We further observed that ghrelin upregulated Aurora A at the protein and RNA levels and that ghrelin-induced ccRCC in vitro invasion and in vivo metastasis occurred in an Aurora A-dependent manner. Furthermore, MMP1, 2, 9 and 10 expressions are associated with poor outcome. In particular, MMP10 is significantly upregulated and required for the ghrelin-Aurora A axis to promote ccRCC invasion. The results of this study indicated a novel signaling mechanism in ccRCC metastasis.
Evolutionary genomics of gypsy moth populations sampled along a latitudinal gradient

The European gypsy moth (Lymantria dispar L.) was first introduced to Massachusetts in 1869 and within 150 years has spread throughout eastern North America. This large‐scale invasion across a heterogeneous landscape allows examination of the genetic signatures of adaptation potentially associated with rapid geographical spread. We tested the hypothesis that spatially divergent natural selection has driven observed changes in three developmental traits that were measured in a common garden for 165 adult moths sampled from six populations across a latitudinal gradient covering the entirety of the range. We generated genotype data for 91,468 single nucleotide polymorphisms based on double digest restriction‐site associated DNA sequencing and used these data to discover genome‐wide associations for each trait, as well as to test for signatures of selection on the discovered architectures. Genetic structure across the introduced range of gypsy moth was low in magnitude (FST = 0.069), with signatures of bottlenecks and spatial expansion apparent in the rare portion of the allele frequency spectrum. Results from applications of Bayesian sparse linear mixed models were consistent with the presumed polygenic architectures of each trait. Further analyses indicated spatially divergent natural selection acting on larval development time and pupal mass, with the linkage disequilibrium component of this test acting as the main driver of observed patterns. The populations most important for these signals were two range‐edge populations established less than 30 generations ago. We discuss the importance of rapid polygenic adaptation to the ability of non‐native species to invade novel environments.
Contralateral suppression of otoacoustic emissions in a clinical sample of children with auditory processing disorder

Abstract Objective: The suppression of evoked otoacoustic emissions (EOAE) may serve as a clinical tool to evaluate the medial olivocochlear (MOC) reflex, which is thought to aid speech discrimination (particularly in noise) by selectively inhibiting cochlear amplification. The present study aimed to determine if contralateral transient evoked otoacoustic emission (TEOAE) suppression was present in a clinical sample of children with listening difficulties with and without auditory processing disorder (APD). Design: A three-group, repeated measure design was used. Study sample: Forty three children aged 8–14 years underwent an auditory processing assessment and were divided into three groups: children with reported listening difficulties with APD, children with reported listening difficulties without APD, and children with normal hearing. APD was defined as per British Society of Audiology. Results: TEOAE suppression was present in all three participant groups. No significant group, age or ear effects were observed for TEOAE suppression in dB or as a normalised index. Conclusion: Contralateral TEOAE suppression method could not be used as a clinical tool to identify APD in this study’s participating children and did not support the hypothesised link between reduced MOC function and general listening difficulties in background noise in children with or without APD.
Increased fraction of exhaled nitric oxide predicts new-onset wheeze in a general population.

RATIONALE Fraction of exhaled nitric oxide (Fe(NO)) is regarded as a marker of airway inflammation. It is unknown whether increased Fe(NO) in respiratorily healthy subjects increases the risk of developing wheeze. OBJECTIVES To examine if increased levels of Fe(NO) predicts later onset of wheeze. METHODS We followed up 2,200 men and women from a general population-based study. At baseline, the subjects were investigated with questionnaires, blood samples, pulmonary function tests, and Fe(NO). At follow-up 4 years later, all subjects were mailed a respiratory questionnaire. The association between incident wheeze and baseline levels of Fe(NO) over the 90th percentile were evaluated calculating hazard ratios using Cox regression models adjusted for smoking habits, age, height, sex, and atopy. MEASUREMENTS AND MAIN RESULTS The follow-up questionnaire was completed by 1,896 subjects (86.2%). All subjects reporting wheeze, asthma, or asthma symptoms at baseline were excluded resulting in a study population of 1,506 subjects. Of these, 49 subjects reported new-onset wheeze. The median concentration of Fe(NO) at baseline was significantly higher among those with new-onset wheeze (18.8 ppb vs. 15.8 ppb, P = 0.03). In a Cox regression model including all subjects, Fe(NO) over the 90th percentile predicted onset of wheeze (hazard ratio 2.7; 95% confidence interval, 1.4-5.4). In stratified models, this was most apparent among never-smokers and in atopic subjects, for whom the odds ratios were higher. CONCLUSIONS Our results indicate that increased Fe(NO) is associated with an increased risk of developing wheeze. The results also support the hypothesis that increased level of Fe(NO) among subjects without respiratory symptoms is a sign of subclinical airways inflammation.
Novel contribution of epigenetic changes to nuclear dynamics

ABSTRACT Migrating cells have to cross many physical barriers and confined in 3D environments. The surrounding environment promotes mechano- and biological signals that orchestrate cellular changes, such as cytoskeletal and adhesion rearrangements and proteolytic digestion. Recent studies provide new insights into how the nucleus must alter its shape, localization and mechanical properties in order to promote nuclear deformability, chromatin compaction and gene reprogramming. It is known that the chromatin structure contributes directly to genomic and non-genomic functions, such as gene transcription and the physical properties of the nucleus. Here, we appraise paradigms and novel insights regarding the functional role of chromatin during nuclear deformation. In so doing, we review how constraint and mechanical conditions influence the structure, localization and chromatin decompaction. Finally, we highlight the emerging roles of mechanogenomics and the molecular basis of nucleoskeletal components, which open unexplored territory to understand how cells regulate their chromatin and modify the nucleus.
Assessing the cost-effectiveness of a fluoride varnish programme in Chile: The use of a decision analytic model in dentistry.

OBJECTIVES This study illustrates the use of a decision analytic model (DAM) to evaluate whether fluoride varnish application (FV) increases the proportion of caries-free children in the Chilean preschool population, at an acceptable cost. METHODS Different FV interventions were compared with an oral health counselling-only intervention. The FV interventions were tested (with and without screening) every 6 months over 2 years, in either a preschool setting or during a well-child programme appointment in a primary care setting. A Markov model was developed to simulate the FV performance. The model was populated with data obtained from Chilean epidemiologic studies, a systematic review and a costing study. The counselling-only intervention was compared with FV interventions to estimate the incremental cost per child. As there was uncertainty in terms of precise parameter values both probabilistic and deterministic sensitivity analyses were performed. RESULTS Delivery of FV in a primary care setting without screening was the most effective and the least costly intervention. Compared with counselling-only intervention, this intervention increased the prevalence of caries-free children in the population by 3.7%, with an extra cost (in March 2015) of £3 per caries-free child. The results were sensitive to the starting age of FV application; increasing age would reduce the cost-effectiveness of the FV intervention. Furthermore, cost-effectiveness improves if some equipment such as an oral hygiene kit was not used and if less costly but qualified staff applied FV rather than dentists. CONCLUSIONS This analysis allowed the comparison of the performance of FV in realistic scenarios incorporating important aspects of health and education policies. The application of FV in a primary care setting was the most cost-effective strategy. The work demonstrated that both the methodology and results are useful for decision-makers.
Tumor Energy Metabolism and Potential of 3-Bromopyruvate as an Inhibitor of Aerobic Glycolysis: Implications in Tumor Treatment

Tumor formation and growth depend on various biological metabolism processes that are distinctly different with normal tissues. Abnormal energy metabolism is one of the typical characteristics of tumors. It has been proven that most tumor cells highly rely on aerobic glycolysis to obtain energy rather than mitochondrial oxidative phosphorylation (OXPHOS) even in the presence of oxygen, a phenomenon called “Warburg effect”. Thus, inhibition of aerobic glycolysis becomes an attractive strategy to specifically kill tumor cells, while normal cells remain unaffected. In recent years, a small molecule alkylating agent, 3-bromopyruvate (3-BrPA), being an effective glycolytic inhibitor, has shown great potential as a promising antitumor drug. Not only it targets glycolysis process, but also inhibits mitochondrial OXPHOS in tumor cells. Excellent antitumor effects of 3-BrPA were observed in cultured cells and tumor-bearing animal models. In this review, we described the energy metabolic pathways of tumor cells, mechanism of action and cellular targets of 3-BrPA, antitumor effects, and the underlying mechanism of 3-BrPA alone or in combination with other antitumor drugs (e.g., cisplatin, doxorubicin, daunorubicin, 5-fluorouracil, etc.) in vitro and in vivo. In addition, few human case studies of 3-BrPA were also involved. Finally, the novel chemotherapeutic strategies of 3-BrPA, including wafer, liposomal nanoparticle, aerosol, and conjugate formulations, were also discussed for future clinical application.
Oral Glutamine Supplementation Reduces Obesity, Pro-Inflammatory Markers, and Improves Insulin Sensitivity in DIO Wistar Rats and Reduces Waist Circumference in Overweight and Obese Humans

In the present study, we aimed to investigate whether chronic oral glutamine (Gln) supplementation may alter metabolic parameters and the inflammatory profile in overweight and obese humans as well as whether Gln may modulate molecular pathways in key tissues linked to the insulin action in rats. Thirty-nine overweight/obese volunteers received 30 g of Gln or alanine (Ala-control) for 14 days. Body weight (BW), waist circumference (WC), hormones, and pro-inflammatory markers were evaluated. To investigate molecular mechanisms, Gln or Ala was given to Wistar rats on a high-fat diet (HFD), and metabolic parameters, euglycemic hyperinsulinemic clamp with tracers, and Western blot were done. Gln reduced WC and serum lipopolysaccharide (LPS) in overweight volunteers. In the obese group, Gln diminished WC and serum insulin. There was a positive correlation between the reduction on WC and LPS. In rats on HFD, Gln reduced adiposity, improved insulin action and signaling, and reversed both defects in glucose metabolism in the liver and muscle. Gln supplementation increased muscle glucose uptake and reversed the increased hepatic glucose production, in parallel with a reduced glucose uptake in adipose tissue. This insulin resistance in AT was accompanied by enhanced IRS1 O-linked-glycosamine association in this tissue, but not in the liver and muscle. These data suggest that Gln supplementation leads to insulin resistance specifically in adipose tissue via the hexosamine pathway and reduces adipose mass, which is associated with improvement in the systemic insulin action. Thus, further investigation with Gln supplementation should be performed for longer periods in humans before prescribing as a beneficial therapeutic approach for individuals who are overweight and obese.
Injury Occurrence and Return to Dance in Professional Ballet: Prospective Analysis of Specific Correlates

Professional ballet is a highly challenging art, but studies have rarely examined factors associated with injury status in ballet professionals. This study aimed to prospectively examine gender-specific correlates of injury occurrence and time-off from injury in professional ballet dancers over a one-year period. The participants were 99 professional ballet dancers (41 males and 58 females). Variables included: (i) predictors: sociodemographic data (age, educational status), ballet-related factors (i.e., experience in ballet, ballet status), cigarette smoking, alcohol drinking, and consumption of illicit drugs; and (ii) outcomes: injury occurrence and time-off from injury. Participants were questioned on predictors at the beginning of the season, while data on outcomes were collected continuously once per month over the study period. Dancers reported total of 196 injuries (1.9 injuries (95% CI: 1.6–2.3) per dancer in average), corresponding to 1.4 injuries per 1000 dance-hours (95% CI: 1.1–1.7). In females, cigarette smoking was a predictor of injury occurrence in females (OR: 4.33, 95% CI: 1.05–17.85). Alcohol drinking was a risk factor for absence from dance in females (OR: 1.29, 95% CI: 1.01–4.21) and males (OR: 1.21, 95% CI: 1.05–3.41). Less experienced dancers were more absent from dance as a result of injury than their more experienced peers (Mann-Whitney Z: 2.02, p < 0.04). Ballet dancers and their managers should be aware of the findings of this study to make informed decisions on their behavior (dancers) or to initiate specific programs aimed at the prevention of substance use and misuse in this profession (managers).
Specific Interactions between Human Norovirus and Environmental Matrices: Effects on the Virus Ecology

Human norovirus is the major cause of non-bacterial epidemic gastroenteritis. Human norovirus binds to environmental solids via specific and non-specific interactions, and several specific receptors for human norovirus have been reported. Among them, histo-blood group antigens (HBGA) are the most studied specific receptor. Studies have identified the presence of HBGA-like substances in the extracellular polymeric substances (EPS) and lipopolysaccharides (LPS) of human enteric bacteria present in aquatic environments, gastrointestinal cells, gills, and palps of shellfish, and cell walls, leaves, and veins of lettuce. These HBGA-like substances also interact with human norovirus in a genotype-dependent manner. Specific interactions between human norovirus and environmental matrices can affect norovirus removal, infectivity, inactivation, persistence, and circulation. This review summarizes the current knowledge and future directions related to the specific interactions between human norovirus and HBGA-like substances in environmental matrices and their possible effects on the fate and circulation of human norovirus.