Miracle-dz/UniFAR-FTUs huggingface dataset:
A Maternal High-Fat Diet during Early Development Provokes Molecular Changes Related to Autism Spectrum Disorder in the Rat Offspring Brain

Autism spectrum disorder (ASD) is a disruptive neurodevelopmental disorder manifested by abnormal social interactions, communication, emotional circuits, and repetitive behaviors and is more often diagnosed in boys than in girls. It is postulated that ASD is caused by a complex interaction between genetic and environmental factors. Epigenetics provides a mechanistic link between exposure to an unbalanced maternal diet and persistent modifications in gene expression levels that can lead to phenotype changes in the offspring. To better understand the impact of the early development environment on the risk of ASD in offspring, we assessed the effect of maternal high-fat (HFD), high-carbohydrate, and mixed diets on molecular changes in adolescent and young adult offspring frontal cortex and hippocampus. Our results showed that maternal HFD significantly altered the expression of 48 ASD-related genes in the frontal cortex of male offspring. Moreover, exposure to maternal HFD led to sex- and age-dependent changes in the protein levels of ANKRD11, EIF4E, NF1, SETD1B, SHANK1 and TAOK2, as well as differences in DNA methylation levels in the frontal cortex and hippocampus of the offspring. Taken together, it was concluded that a maternal HFD during pregnancy and lactation periods can lead to abnormal brain development within the transcription and translation of ASD-related genes mainly in male offspring.
Polydatin Counteracts 5-Fluorouracil Resistance by Enhancing Apoptosis via Calcium Influx in Colon Cancer

Colon cancer is a disease with a high prevalence rate worldwide, and for its treatment, a 5-fluorouracil (5-FU)-based chemotherapeutic strategy is generally used. However, conventional anticancer agents have some limitations, including the development of drug resistance. Therefore, there has recently been a demand for the improvement of antitumor agents using natural products with low side effects and high efficacy. Polydatin is a natural active compound extracted from an annual plant, and widely known for its anticancer effects in diverse types of cancer. However, it is still not clearly understood how polydatin ameliorates several drawbacks of standard anticancer drugs by reinforcing the chemosensitivity against 5-FU, and neither are the intrinsic mechanisms behind this process. In this study, we examined how polydatin produces anticancer effects in two types of colon cancer, called HCT116 and HT-29 cells. Polydatin has the ability to repress the progression of colon cancer, and causes a modification of distribution in the cell cycle by a flow cytometry analysis. It also induces mitochondrial dysfunctions through oxidative stress and the loss of mitochondrial membrane potential. The present study investigated the apoptosis caused by the disturbance of calcium regulation and the expression levels of related proteins through flow cytometry and immunoblotting analysis. It was revealed that polydatin suppresses the signaling pathways of the mitogen-activated protein kinase (MAPK) and PI3K/AKT. In addition, it was shown that polydatin combined with 5-FU counteracts drug resistance in 5-FU-resistant cells. Therefore, this study suggests that polydatin has the potential to be developed as an innovative medicinal drug for the treatment of colon cancer.
Tumor-Associated Macrophages in Bladder Cancer: Biological Role, Impact on Therapeutic Response and Perspectives for Immunotherapy

Simple Summary Tumor-associated macrophages (TAMs) play major roles in solid tumor development. They can have both anti-tumor and pro-tumor properties depending on their polarization. In this review, we summarize the observations and associations made between the presence of TAMs and their subtypes within bladder cancer and the type of disease, its evolution, the prognostic value for patients and the impact on current treatments. Only few studies focused on the effect of targeting TAMs in bladder cancer thus far. We propose several potential targets/treatments that may benefit for the limitation of pro-tumor TAMs and thus for the improvement of bladder cancer therapies. Abstract Tumor-associated macrophages (TAMs) are one of the most abundant infiltrating immune cells of solid tumors. Despite their possible dual role, i.e., pro- or anti-tumoral, there is considerable evidence showing that the accumulation of TAMs promotes tumor progression rather than slowing it. Several strategies are being developed and clinically tested to target these cells. Bladder cancer (BCa) is one of the most common cancers, and despite heavy treatments, including immune checkpoint inhibitors (ICIs), the overall patient survival for advanced BCa is still poor. TAMs are present in bladder tumors and play a significant role in BCa development. However, few investigations have analyzed the effect of targeting TAMs in BCa. In this review, we focus on the importance of TAMs in a cancerous bladder, their association with patient outcome and treatment efficiency as well as on how current BCa treatments impact these cells. We also report different strategies used in other cancer types to develop new immunotherapeutic strategies with the aim of improving BCa management through TAMs targeting.
The Impact of Package Type and Temperature on the Changes in Quality and Fatty Acids Profile of Table Eggs during Their Storage

The aim of the study was to evaluate the possibility of reducing changes in the quality of consumer hen eggs by storing them in various package type and under various temperature conditions (room and refrigeration). The material consisted of 960 chicken eggs packed in cardboard or plastic boxes, 10 pcs in each. Half of the packages were stored at room temperature (21 °C), the rest in the refrigerator (5 °C). The eggs were stored for 28 days qualitatively evaluated at 14-day intervals. The characteristics of whole egg (weight, specific weight, proportion of morphological elements, air cell depth) as well as of shell (weight, color, crushing strength, thickness, density, water conductivity), albumen (height, Haugh units, weight, pH) and yolk (weight, color, pH) were analyzed. The fatty acids profile of yolks was also evaluated as a freshness indicator. Packaging types available on the market, apart from its marketing and eggs protection function, can also influence the quality and stability of the product during storage. The use of plastic boxes can help to maintain higher eggs quality during the storage period, even after a significant extension of the storage time. Eggs stored in plastic boxes at room temperature had very similar results to those stored under refrigeration using conventional cardboard boxes. This effect is probably related to the lower permeability of plastic boxes in comparison to cardboard ones, but detailed research work in this direction is necessary to verify this relation.
Perinatal Resveratrol Therapy to Dioxin-Exposed Dams Prevents the Programming of Hypertension in Adult Rat Offspring

Exposure to environmental chemicals during pregnancy and lactation is a contributing factor in gut microbiota dysbiosis and linked to programming of hypertension. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic dioxin, induces toxic effects by mediating aryl hydrocarbon receptor (AHR). Resveratrol, a potent antioxidant with prebiotic properties, can possess high affinity for AHR and protect against TCDD-activated AHR attack. We examined whether perinatal resveratrol therapy prevents offspring hypertension programmed by maternal TCDD exposure and whether its beneficial effects are related to reshaping gut microbiota and antagonizing AHR-mediated T helper 17 (TH17) cells responses using a maternal TCDD exposure rat model. Pregnant Sprague-Dawley rats were given a weekly oral dose of TCDD 200 ng/kg for four doses (T), 50 mg/L of resveratrol in drinking water (CR), TCDD + resveratrol (TR), or vehicle (C) in pregnancy and lactation periods. Male offspring (n = 7–8/group) were sacrificed at the age of 12 weeks. Perinatal TCDD exposure caused elevated blood pressure in adult male offspring, which resveratrol supplementation prevented. Additionally, the TCDD-induced programming of hypertension is coincided with the activation of AHR signaling, TH17-induced renal inflammation, and alterations of gut microbiota compositions. Conversely, TCDD-mediated induction of AHR signaling and TH17 responses were restored by maternal resveratrol supplementation. Furthermore, maternal resveratrol supplementation prevented the programming of hypertension and was related to increased genera Bacteroides, ASF356, and Lachnoclostridium. Taken together, these results suggest that the interplay between gut microbiota, AHR-mediated TH17 responses, and renal inflammation in the gut and kidneys may play an important role in the action of resveratrol against TCDD-induced programming of hypertension.
Association between Physical Activity and Sleep Difficulties among Adolescents in Germany: The Role of Socioeconomic Status

We examined sleep difficulties among adolescents in Germany and the association with physical activity (PA). Furthermore, we analyzed whether the association varied with the socioeconomic status (SES) among adolescent girls and boys in Germany. Using data from the German Health Interview Examination Survey for Children and Adolescents (KiGGS) study (Wave 2), 6599 adolescents aged 11 to 17 years were included in the analyses. We conducted sex-stratified logistic regression analyses. Dependent variables were unrecommended sleep duration (defined as a duration of sleep that does not meet the recommended duration), sleep-onset difficulties, trouble sleeping, and daytime sleepiness. Most adolescent girls and boys reported sleep difficulties. While no associations between PA and sleep difficulties were observed, a significant interaction between PA and SES was found for sleep duration in boys and daytime sleepiness in girls. Thus, adolescents with low SES had fewer sleep difficulties if they met the recommendation for PA, compared with those in other SES groups. In Germany, a large proportion of adolescents have sleep difficulties. We found that the experience of sleep difficulties varied according to PA, sex, and the family SES. Future sleep promotion programs should consider these differences.
Predictors of Early and Late Mortality for Patients with Hematologic Malignancy and Invasive Mold Disease

Background: Invasive mold infections (IMI) are leading infectious causes of mortality among patients with hematological malignancies. Objectives: To determine the relative contribution of host, disease, and treatment-related factors to patient survival. Methods: An observational, retrospective cohort study reviewing the medical records of patients with hematological malignancy and IMI (2006–2016). Causes of death were classified up to 90 days after diagnosis. Kaplan–Meier and Cox regression analyses were used to determine risk factors for early, late, and overall mortality. Results: Eighty-six patients with IMI were included; 29 (34%) and 41 (47%) died within 6 and 12 weeks of diagnosis, respectively. Death was attributed to IMI in 22 (53.6%) patients, all of whom died within 45 days of diagnosis. Risk factors for early mortality were elevated serum galactomannan, treatment with amphotericin B, IMI progression 3 weeks after diagnosis, and lymphoma undergoing HCT. Late mortality was associated with relapsed/refractory malignancy and elevated serum galactomannan. Conclusions: In this single-center study of patients with IMI, infections were the most frequent causes of death, and time-dependent risk factors for death were identified. These results may help direct risk-assessment and monitoring of patients undergoing treatment of IMI.
Social Acceptance of Gas, Wind, and Solar Energies in the Canary Islands

Background: This study tested a theoretical model including key psychosocial factors that could be involved in the acceptance of different energy sources (gas, wind, and solar); Methods: Participants were 550 adult residents of the Canary Islands. Variables assessed were information and utility (normative motives), perceived risk and perceived benefits (gain motives), and negative and positive emotions (hedonic motives), with acceptance of each of the three energy sources as outcome variables; Results: It was found that renewable energies (wind and solar) had a higher degree of acceptance than non-renewable energy (gas). The proposed model satisfactorily explained the social acceptance of the three energy sources, although the psychosocial factors involved differed by energy source. The gain motives, mainly perceived benefits, were associated to a greater extent with gas energy, whereas normative motives, such as utility, and hedonic motives, such as positive emotions, had greater weight for renewables. Gender differences in gas energy were found. Information about renewable energy increased positive emotions and acceptance, whereas information about fossil fuel-based energy generated more negative emotions and perceived risk, decreasing acceptance; Conclusions: Utility, perceived benefits and positive emotions were involved on the acceptance of both renewables and non-renewables. The theoretical model tested seems to be useful for understanding the psychosocial functioning of the acceptance of the various energy sources as an essential aspect for the transition of non-renewable to renewable energies.
Anti-Inflammatory Effect of Charantadiol A, Isolated from Wild Bitter Melon Leaf, on Heat-Inactivated Porphyromonas gingivalis-Stimulated THP-1 Monocytes and a Periodontitis Mouse Model

Porphyromonas gingivalis has been identified as one of the major periodontal pathogens. Activity-directed fractionation and purification processes were employed to identify bioactive compounds from bitter melon leaf. Ethanolic extract of bitter melon leaf was separated into five subfractions by open column chromatography. Subfraction-5-3 significantly inhibited P. gingivalis-induced interleukin (IL)-8 and IL-6 productions in human monocytic THP-1 cells and then was subjected to separation and purification by using different chromatographic methods. Consequently, 5β,19-epoxycucurbita-6,23(E),25(26)-triene-3β,19(R)-diol (charantadiol A) was identified and isolated from the subfraction-5-3. Charantadiol A effectively reduced P. gingivalis-induced IL-6 and IL-8 productions and triggered receptors expressed on myeloid cells (TREM)-1 mRNA level of THP-1 cells. In a separate study, charantadiol A significantly suppressed P. gingivalis-stimulated IL-6 and tumor necrosis factor-α mRNA levels in gingival tissues of mice, confirming the inhibitory effect against P. gingivalis-induced periodontal inflammation. Thus, charantadiol A is a potential anti-inflammatory agent for modulating P. gingivalis-induced inflammation.
Integrating Dietary Data into Microbiome Studies: A Step Forward for Nutri-Metaomics

Diet is recognised as the main driver of changes in gut microbiota. However, linking habitual dietary intake to microbiome composition and activity remains a challenge, leaving most microbiome studies with little or no dietary information. To fill this knowledge gap, we conducted two consecutive studies (n = 84: a first pilot study (n = 40) to build a web-based, semi-quantitative simplified FFQ (sFFQ) based on three 24-h dietary recalls (24HRs); a second study (n = 44) served to validate the newly developed sFFQ using three 24HRs as reference method and to relate gut microbiome profiling (16S rRNA gene) with the extracted dietary and lifestyle data. Relative validation analysis provided acceptable classification and agreement for 13 out of 24 (54%) food groups and 20 out of 29 nutrients (69%) based on intraclass correlation coefficient, cross-classification, Spearman’s correlation, Wilcoxon test, and Bland–Altman. Microbiome analysis showed that higher diversity was positively associated with age, vaginal birth, and intake of fruit. In contrast, microbial diversity was negatively associated with BMI, processed meats, ready-to-eat meals, sodium, and saturated fat. Our analysis also revealed a correlation between food groups or nutrients and microbial composition. Overall, we provide the first dietary assessment tool to be validated and correlated with microbiome data for population studies.
Self-Sensing Cementitious Composites: Review and Perspective

Self-sensing concrete (SSC) has been vastly studied for its possibility to provide a cost-effective solution for structural health monitoring of concrete structures, rendering it very attractive in real-life applications. In this review paper, comprehensive information about the components of self-sensing concrete, dispersion methods and mix design, as well as the recent progress in the field of self-sensing concrete, has been provided. The information and recent research findings about self-sensing materials for smart composites, their properties, measurement of self-sensing signal and the behavior of self-sensing concrete under different loading conditions are included. Factors influencing the electrical resistance of self-sensitive concrete such as dry-wet cycle, ice formation and freeze thaw cycle and current frequency, etc., which were not covered by previous review papers on self-sensing concrete, are discussed in detail. Finally, major emphasis is placed on the application of self-sensing technology in existing and new structures.
Efficacy and Safety of Insulin Degludec/Insulin Aspart Compared with a Conventional Premixed Insulin or Basal Insulin: A Meta-Analysis

Insulin degludec/insulin aspart (IDegAsp) is a novel co-formulation of 70% insulin degludec and 30% insulin aspart. The present meta-analysis was conducted to assess the efficacy and safety of IDegAsp compared with a conventional premixed insulin or basal insulin. We extracted data from citation databases, including PubMed, EMBASE, and the Cochrane Library, since inception to 2021. We calculated the mean differences for hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), self-measured mean glucose, and postprandial glucose (PPG) and odds ratios for confirmed hypoglycemia events. Compared with twice-daily conventional premixed insulin, twice-daily IDegAsp showed a similar effect on changes in HbA1c, but it significantly reduced FPG and self-measured mean glucose levels. Furthermore, compared to once-daily basal insulin, once-daily IDegAsp had a similar effect on changes in HbA1c, but it significantly reduced self-measured mean glucose and PPG levels. The risk of overall confirmed hypoglycemia was similar between treatments; however, the risk of nocturnal hypoglycemia events was significantly lower with IDegAsp than with conventional premixed insulin and basal insulin. Thus, IDegAsp was more effective than conventional premixed insulin and basal insulin at reducing blood glucose with fewer nocturnal hypoglycemia events.
Evaluation of the Correlation between the mRNA Expression Levels of ystA and ymoA Genes in Y. enterocolitica Strains with Different Enterotoxic Properties

Yersinia enterocolitica is one of the main causative agents of human diarrhea. Pigs are a reservoir and the most common source of infection for humans. The aim of this study was to analyze the expression of ystA and ymoA genes in Y. enterocolitica strains with different enterotoxic properties, isolated from humans and pigs. The experiment involved two groups of Y. enterocolitica strains producing and not producing enterotoxin YstA, which were isolated from humans and pigs. All strains were ystA- and ymoA-positive. The expression of ystA and ymoA genes was analyzed by quantitative real-time PCR (qPCR). The relative expression level of the ystA gene was significantly higher than the expression level of the ymoA gene in Y. enterocolitica strains isolated from humans with clinical symptoms of yersiniosis. In other strains, a significant decrease in ystA gene transcription was observed, and the relative expression level of the ymoA gene was significantly higher than the expression level of the ystA gene. Statistically significant differences were not observed in either group of strains isolated from pigs. The results of our study revealed a correlation between mRNA expression levels of ystA and ymoA genes in Y. enterocolitica strains isolated from humans.
Differential Regulation of Circulating Soluble Receptor for Advanced Glycation End Products (sRAGEs) and Its Ligands S100A8/A9 Four Weeks Post an Exercise Intervention in a Cohort of Young Army Recruits

Apart from its beneficial effects on cardiovascular risk factors, an anti-inflammatory effect of exercise is strongly implicated. Yet, data regarding the effect of an exercise intervention on healthy individuals are limited and contradictory. The present study aimed to investigate the effects of a physical activity intervention on the soluble form of the receptor for advanced glycation end products (sRAGEs) and its ligands S100A8/A9. A total of 332 young army recruits volunteered and 169 completed the study. The participants underwent the standard basic training of Greek army recruits. IL-6, IL-1β, S100A8/A9, and sRAGEs were measured at the beginning and at the end of the training period. Primary rodent adult aortic smooth muscle cells (ASMCs) were analyzed for responsiveness to direct stimulation with S100A8/A9 alone or in combination with sRAGEs. At the end of the training period, we observed a statistically significant reduction in S100A8/A9 (630.98 vs. 472.12 ng/mL, p = 0.001), IL-1β (9.39 [3.8, 44.14] vs. 5.03 [2.44, 27.3] vs. pg/mL, p = 0.001), and sRAGEs (398.38 vs. 220.1 pg/mL, p = 0.001). IL-6 values did not change significantly after exercise. S100A8/A9 reduction was positively correlated with body weight (r = 0.236 [0.095, 0.370], p = 0.002) and BMI (r = 0.221 [0.092, 0.346], p = 0.004). Direct stimulation of ASMCs with S100A8/A9 increased the expression of IL-6, IL-1β, and TNF-α and, in the presence of sRAGEs, demonstrated a dose-dependent inhibition. A 4-week military training resulted in significant reduction in the pro-inflammatory cytokines IL-1β and S100A8/A9 complex. The observed reduction in sRAGEs may possibly reflect diminished RAGE axis activation. Altogether, our findings support the anti-inflammatory properties of physical activity.
Histologic Transformation in EGFR-Mutant Lung Adenocarcinomas: Mechanisms and Therapeutic Implications

Simple Summary Despite being effective initially, almost all patients eventually develop resistance to EGFR-tyrosine kinase inhibitors (TKI). Changes in the histology of the tumor have been increasingly recognized as a critical mechanism of resistance to EGFR-directed therapies. This article summarizes histologic changes known to impart resistance to EGFR TKIs and discusses novel pathways to develop effective novel therapies. Abstract With the advent of potent EGFR tyrosine kinase inhibitors (TKIs), the treatment landscape of EGFR-mutant lung adenocarcinomas has changed drastically in recent years. However, the development of resistance to EGFR TKIs remains a critical barrier to improving survival in these patients. Histologic transformations to small cell lung carcinoma, large cell neuroendocrine carcinoma, squamous cell carcinoma, and the sarcomatoid phenotype have been increasingly recognized as important mechanisms of resistance. In this article, we summarize the known biological bases for such phenotypic switches in regard to EGFR TKIs and describe novel pathways that might be harnessed to develop effective novel therapies for patients with EGFR-mutant non-small cell lung cancers.