Miracle-dz/UniFAR-FTUs huggingface dataset:
Primary and Memory Response of Human Monocytes to Vaccines: Role of Nanoparticulate Antigens in Inducing Innate Memory

Innate immune cells such as monocytes and macrophages are activated in response to microbial and other challenges and mount an inflammatory defensive response. Exposed cells develop the so-called innate memory, which allows them to react differently to a subsequent challenge, aiming at better protection. In this study, using human primary monocytes in vitro, we have assessed the memory-inducing capacity of two antigenic molecules of Schistosoma mansoni in soluble form compared to the same molecules coupled to outer membrane vesicles of Neisseria lactamica. The results show that particulate challenges are much more efficient than soluble molecules in inducing innate memory, which is measured as the production of inflammatory and anti-inflammatory cytokines (TNFα, IL-6, IL-10). Controls run with LPS from Klebsiella pneumoniae compared to the whole bacteria show that while LPS alone has strong memory-inducing capacity, the entire bacteria are more efficient. These data suggest that microbial antigens that are unable to induce innate immune activation can nevertheless participate in innate activation and memory when in a particulate form, which is a notion that supports the use of nanoparticulate antigens in vaccination strategies for achieving adjuvant-like effects of innate activation as well as priming for improved reactivity to future challenges.
Role of Neonatal Biomarkers of Exposure to Psychoactive Substances to Identify Maternal Socio-Demographic Determinants

Simple Summary The rapid identification of newborns exposure to psychoactive drugs allows an appropriate clinical care. This study tried to identify maternal profiles that help to identify newborns exposed to psychoactive drugs during pregnancy. Mothers were interviewed using a questionnaire. The biomarkers of fetal exposure were measured in meconium samples. Statistical analysis was performed to identify the maternal characteristics that were most likely to be associated with drug use during pregnancy. Of a total of 372 mothers, 49 (13.2%) tested positive for psychoactive drugs use: 24 (49.0%) for cannabis, 11 (22.5%) for ethyl glucuronide, six (12.2%) for cocaine, and eight (16.3%) for more than one psychoactive substance. The maternal characteristics that most likely identify substance use during pregnancy are: maternal age < 24 years, lack of pregnancy care, single-mother families, and active tobacco smoking. The profiles of prenatal maternal exposure identified in a clinical setting can be used to request specific detection tests for identifying newborns exposed to these drugs. Abstract Background: The accurate assessment of fetal exposure to psychoactive substances provides the basis for appropriate clinical care of neonates. The objective of this study was to identify maternal socio-demographic profiles and risk factors for prenatal exposure to drugs of abuse by measuring biomarkers in neonatal matrices. Methods: A prospective, observational cohort study was completed. Biomarkers of fetal exposure were measured in meconium samples. The mothers were interviewed using a questionnaire. Univariate and multivariate logistic regression analyses were performed. Results: A total of 372 mothers were included, 49 (13.2%) testing positive for psychoactive substances use: 24 (49.0%) for cannabis, 11 (22.5%) for ethyl glucuronide, six (12.2%) for cocaine, and in eight (16.3%) more than one psychoactive substance. Mothers who consumed any psychoactive substance (29.7 ± 6.6 years) or cannabis (27.0 ± 5.7 years) were younger than non-users (32.8 ± 6.2 years, p < 0.05). Cocaine (50.0% vs. 96.9%, p < 0.05) and polydrug users (37.5% vs. 96.9%, p < 0.05) showed a lower levels of pregnancy care. Previous abortions were associated with the use of two or more psychoactive substances (87.5% vs. 37.8%, p < 0.05). Single-mother families (14.3% vs. 2.5%, p < 0.05) and mothers with primary level education (75.5% vs. 55.1%, p < 0.05) presented a higher consumption of psychoactive substances. Independent risk factors that are associated with prenatal exposure include: maternal age < 24 years (odds ratio: 2.56; 95% CI: 1.12–5.87), lack of pregnancy care (odds ratio: 7.27; 95%CI: 2.51–21.02), single-mother families (odds ratio: 4.98; 95%CI: 1.37–8.13), and active tobacco smoking (odds ratio: 8.13; 95%CI: 4.03–16.43). Conclusions: These results will allow us to develop several risk-based drug screening approaches to improve the early detection of exposed neonates.
Doses de superfosfato simples na produção da berinjela ‘ciça’ em cassilândia (MS) Brasil

O objetivo deste experimento foi avaliar a resposta da berinjela ( Solanum melongena L.) submetida a diferentes doses de fosforo aplicadas na cova de plantio. Os tratamentos foram compostos por quatro doses de superfosfato simples (0, 1000, 2000, 3000 kg ha -1 ; o experimento foi conduzido no delineamento experimental em blocos casualizados, com cinco repeticoes, tendo cada unidade experimental quatro plantas. A adubacao fosfatada propiciou aumento do diâmetro do colo da planta adulta, do numero de frutos por planta e produtividade de frutos; podendo ser utilizada doses entre 1814 a 2054 kg.ha -1 de superfosfato simples nas condicoes de Cassilândia (MS). Palavras-chave : Adubacao fosfatada; caracteristicas de frutos ; Solanum melongena L.
The rs599839 A>G Variant Disentangles Cardiovascular Risk and Hepatocellular Carcinoma in NAFLD Patients

Simple Summary Dyslipidemia is a hallmark of nonalcoholic fatty liver disease (NAFLD) and the rs599839 variant in the CELSR2-PSRC1-SORT1 genetic cluster, has been associated with a protection against cardiovascular events. Here, we revealed a novel link between the rs599839 variant and hepatocellular carcinoma (HCC) whose onset in the context of NAFLD is rapidly increasing. We found that the rs599839 variant disentangled the risk of HCC from that of cardiovascular abnormalities by modulating SORT1 and PSRC1 expressions. The latter emerged as a potential modifier of liver carcinogenesis. Abstract Background and Aims: Dyslipidemia and cardiovascular diseases (CVD) are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from steatosis to hepatocellular carcinoma (HCC). The rs599839 A>G variant, in the CELSR2-PSRC1-SORT1 gene cluster, has been associated CVD, but its impact on metabolic traits and on the severity liver damage in NAFLD has not been investigated yet. Methods: We evaluated the effect of the rs599839 variant in 1426 NAFLD patients (Overall cohort) of whom 131 had HCC (NAFLD-HCC), in 500,000 individuals from the UK Biobank Cohort (UKBBC), and in 366 HCC samples from The Cancer Genome Atlas (TCGA). Hepatic PSRC1, SORT1 and CELSR2 expressions were evaluated by RNAseq (n = 125). Results: The rs599839 variant was associated with reduced circulating LDL, carotid intima-media thickness, carotid plaques and hypertension (p < 0.05) in NAFLD patients and with protection against dyslipidemia in UKBBC. The minor G allele was associated with higher risk of HCC, independently of fibrosis severity (odds ratio (OR): 5.62; 95% c.i. 1.77–17.84, p = 0.003), poor prognosis and advanced tumor stage (p < 0.05) in the overall cohort. Hepatic PSRC1, SORT1 and CELSR2 expressions were increased in NAFLD patients carrying the rs599839 variant (p < 0.0001). SORT1 mRNA levels negatively correlated with circulating lipids and with those of genes involved in lipoprotein turnover (p < 0.0001). Conversely, PSRC1 expression was positively related to that of genes implicated in cell proliferation (p < 0.0001). In TCGA, PSRC1 over-expression promoted more aggressive HCC development (p < 0.05). Conclusions: In sum, the rs599839 A>G variant is associated with protection against dyslipidemia and CVD in NAFLD patients, but as one it might promote HCC development by modulating SORT1 and PSRC1 expressions which impact on lipid metabolism and cell proliferation, respectively.
Reduced Thiamine Availability and Hyperglycemia Impair Thiamine Transport in Renal Glomerular Cells through Modulation of Thiamine Transporter 2

Thiamine helps transketolase in removing toxic metabolites, counteracting high glucose-induced damage in microvascular cells, and progression of diabetic retinopathy/nephropathy in diabetic animals. Diabetic subjects show reduced thiamine levels. Hyperglycemia and reduced thiamine availability concur in impairing thiamine transport inside the blood-retinal barrier, with thiamine transporter-2 (THTR2) primarily involved. Here, we examined the behavior of thiamine transporter-1 (THTR1), THTR2, and their transcription factor Sp1 in response to high glucose and altered thiamine availability in renal cells involved in diabetic nephropathy. Human proximal tubule epithelial cells, podocytes, glomerular endothelial, and mesangial cells were exposed to high glucose and/or thiamine deficiency/oversupplementation. Localization and modulation of THTR1, THTR2, and Sp1; intracellular thiamine; transketolase activity; and permeability to thiamine were examined. Reduced thiamine availability and hyperglycemia impaired thiamine transport and THTR2/Sp1 expression. Intracellular thiamine, transketolase activity, and permeability were strongly dependent on thiamine concentrations and, partly, excess glucose. Glomerular endothelial cells were the most affected by the microenvironmental conditions. Our results confirmed the primary role of THTR2 in altered thiamine transport in cells involved in diabetic microvascular complications. Lack of thiamine concurs with hyperglycemia in impairing thiamine transport. Thiamine supplementation could represent a therapeutic option to prevent or slow the progression of these complications.
Maternal Obesity and Risk of Low Birth Weight, Fetal Growth Restriction, and Macrosomia: Multiple Analyses

The associations between maternal pre-pregnancy obesity and low birth weight (LBW, <2500 g) remain inconclusive. Therefore, birth weight in a Polish prospective cohort of 912 mothers was investigated depending on the pre-pregnancy body mass index (BMI). The whole cohort and the subgroup of gestational weight gain (GWG) in the range of the Institute of Medicine (IOM) recommendations, as well as ‘healthy’ women (who did not develop diabetes or hypertension in this pregnancy) were investigated. Adjusted odds ratios (AOR) of the newborn outcomes (with 95% confidence intervals, CI) for obesity (BMI ≥ 30 kg/m2) vs. normal BMI (18.5−24.9 kg/m2) were calculated using multiple logistic regression. Risk profiles (in the Lowess method) were presented for BMI values (kg/m2) and threshold BMI values were calculated. (1) In the cohort, LBW affected 6.6% of pregnancies, fetal growth restriction (FGR) 2.3%, and macrosomia 10.6%. (2) The adjusted risk of macrosomia was more than three-fold higher for obesity compared to normal BMI in the whole cohort (AOR = 3.21 (1.69−6.1), p < 0.001) and the result was maintained in the subgroups. A 17-fold higher adjusted LBW risk for obesity was found (AOR = 17.42 (1.5−202.6), p = 0.022), but only in the normal GWG subgroup. The FGR risk profile was U-shaped: in the entire cohort, the risk was more than three times higher for obesity (AOR = 3.12 (1.02−9.54), p = 0.045) and underweight (AOR = 3.84 (1.13−13.0), p = 0.031). (3) The risk profiles showed that the highest BMI values were found to be associated with a higher risk of these three newborn outcomes and the threshold BMI was 23.7 kg/m2 for macrosomia, 26.2 kg/m2 for LBW, and 31.8 kg/m2 for FGR. These results confirm the multidirectional effects of obesity on fetal growth (low birth weight, fetal growth restriction, and macrosomia). The results for LBW were heavily masked by the effects of abnormal gestational weight gain.
Neutrophil-to-Lymphocyte Ratio as a Cardiovascular Risk Marker May Be Less Efficient in Women Than in Men

Cardiovascular disease (CVD) is the leading cause of death in women, although traditionally, it has been considered as a male dominated disease. Chronic inflammation plays a crucial role in the development of insulin resistance, diabetes type 2 and CVD. Since studies on women were scarce, in order to improve diagnosis and treatment of CVD, there is a need to improve understanding of the role of inflammation in the development of CVD in women. The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive and widely available marker of inflammation, and has been studied in cardio-metabolic disorders. There is a paucity of data on sex specific differences in the lifetime course of NLR. Men and women differ to each other in sex hormones and characteristics of immune reaction and the expression of CVD. These factors can determine NLR values and their variations along the life course. In particular, menopause in women is a period associated with profound physiological and hormonal changes, and is coincidental with aging. An emergence of CV risk factors with aging, and age-related changes in the immune system, are factors that are associated with an increase in prevalence of CVD in both sexes. The aim of this review is to comprehend the available evidence on this issue, and to discuss sex specific differences in the lifetime course of NLR in the light of immune and inflammation mechanisms.
Adherence and Dietary Composition during Intermittent vs. Continuous Calorie Restriction: Follow-Up Data from a Randomized Controlled Trial in Adults with Overweight or Obesity

Although intermittent calorie restriction (ICR) has become popular as an alternative weight loss strategy to continuous calorie restriction (CCR), there is insufficient evidence on diet quality during ICR and on its feasibility over longer time periods. Thus, we compared dietary composition and adherence between ICR and CCR in a follow-up analysis of a randomized trial. A total of 98 participants with overweight or obesity [BMI (kg/m2) 25–39.9, 35–65 years, 49% females] were randomly assigned to ICR, operationalized as a “5:2 diet” (energy intake: ~100% on five non-restricted (NR) days, ~25% on two restricted (R) days), or CCR (daily energy intake: ~80%). The trial included a 12-week (wk) intervention phase, and follow-up assessments at wk24, wk50 and wk102. Apart from a higher proportion of energy intake from protein with ICR vs. CCR during the intervention (wk2: p < 0.001; wk12: p = 0.002), there were no significant differences with respect to changes in dietary composition over time between the groups, while overall adherence to the interventions appeared to be good. No significant difference between ICR and CCR regarding weight change at wk102 was observed (p = 0.63). However, self-reported adherence was worse for ICR than CCR, with 71.1% vs. 32.5% of the participants reporting not to or only rarely have followed the regimen to which they were assigned between wk50 and wk102. These results indicate that within a weight management setting, ICR and CCR were equivalent in achieving modest weight loss over two years while affecting dietary composition in a comparable manner.
Flavor and Metabolite Profiles of Meat, Meat Substitutes, and Traditional Plant-Based High-Protein Food Products Available in Australia

Demand for plant-based proteins and plant-based food products is increasing globally. This trend is driven mainly by global population growth and a consumer shift towards more sustainable and healthier diets. Existing plant-based protein foods and meat mimetics often possess undesirable flavor and sensory properties and there is a need to better understand the formation of desirable meat-like flavors from plant precursors to improve acceptance of novel high-protein plant foods. This study aimed to comprehensively characterize the non-volatile flavor metabolites and the volatiles generated in grilled meat (beef, chicken, and pork) and compare these to commercially available meat substitutes and traditional high-protein plant-based foods (natto, tempeh, and tofu). Solid phase microextraction with gas-chromatography mass-spectrometry was used for elucidation of the flavor volatilome. Untargeted characterization of the non-volatile metabolome was conducted using Orbitrap mass spectrometry and Compound DiscovererTM datamining software. The study revealed greater diversity and higher concentrations of flavor volatiles in plant-based foods in comparison to grilled meat, although the odor activity of specific volatiles was not considered. On average, the total amount of volatiles in plant-based products were higher than in meat. A range of concentrations of free amino acids, dipeptide, tripeptides, tetrapeptides, nucleotides, flavonoids, and other metabolites was identified in meat and plant-based foods.
Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study

In the present paper, new pyrimidine derivatives were designed, synthesized and analyzed in terms of their anticancer properties. The tested compounds were evaluated in vitro for their antitumor activity. The cytotoxic effect on normal human dermal fibroblasts (NHDF) was also determined. According to the results, all the tested compounds exhibited inhibitory activity on the proliferation of all lines of cancer cells (colon adenocarcinoma (LoVo), resistant colon adenocarcinoma (LoVo/DX), breast cancer (MCF-7), lung cancer (A549), cervical cancer (HeLa), human leukemic lymphoblasts (CCRF-CEM) and human monocytic (THP-1)). In particular, their feature stronger influence on the activity of P-glycoprotein of cell cultures resistant to doxorubicin than doxorubicin. Tested compounds have more lipophilic character than doxorubicin, which determines their affinity for the molecular target and passive transport through biological membranes. Moreover, the inhibitory potential against topoisomerase II and DNA intercalating properties of synthesized compounds were analyzed via molecular docking.
Public-Health-Driven Microfluidic Technologies: From Separation to Detection

Separation and detection are ubiquitous in our daily life and they are two of the most important steps toward practical biomedical diagnostics and industrial applications. A deep understanding of working principles and examples of separation and detection enables a plethora of applications from blood test and air/water quality monitoring to food safety and biosecurity; none of which are irrelevant to public health. Microfluidics can separate and detect various particles/aerosols as well as cells/viruses in a cost-effective and easy-to-operate manner. There are a number of papers reviewing microfluidic separation and detection, but to the best of our knowledge, the two topics are normally reviewed separately. In fact, these two themes are closely related with each other from the perspectives of public health: understanding separation or sorting technique will lead to the development of new detection methods, thereby providing new paths to guide the separation routes. Therefore, the purpose of this review paper is two-fold: reporting the latest developments in the application of microfluidics for separation and outlining the emerging research in microfluidic detection. The dominating microfluidics-based passive separation methods and detection methods are discussed, along with the future perspectives and challenges being discussed. Our work inspires novel development of separation and detection methods for the benefits of public health.
Characterization of the Aerobic Anoxygenic Phototrophic Bacterium Sphingomonas sp. AAP5

An aerobic, yellow-pigmented, bacteriochlorophyll a-producing strain, designated AAP5 (=DSM 111157=CCUG 74776), was isolated from the alpine lake Gossenköllesee located in the Tyrolean Alps, Austria. Here, we report its description and polyphasic characterization. Phylogenetic analysis of the 16S rRNA gene showed that strain AAP5 belongs to the bacterial genus Sphingomonas and has the highest pairwise 16S rRNA gene sequence similarity with Sphingomonas glacialis (98.3%), Sphingomonas psychrolutea (96.8%), and Sphingomonas melonis (96.5%). Its genomic DNA G + C content is 65.9%. Further, in silico DNA-DNA hybridization and calculation of the average nucleotide identity speaks for the close phylogenetic relationship of AAP5 and Sphingomonas glacialis. The high percentage (76.2%) of shared orthologous gene clusters between strain AAP5 and Sphingomonas paucimobilis NCTC 11030T, the type species of the genus, supports the classification of the two strains into the same genus. Strain AAP5 was found to contain C18:1ω7c (64.6%) as a predominant fatty acid (>10%) and the polar lipid profile contained phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, sphingoglycolipid, six unidentified glycolipids, one unidentified phospholipid, and two unidentified lipids. The main respiratory quinone was ubiquinone-10. Strain AAP5 is a facultative photoheterotroph containing type-2 photosynthetic reaction centers and, in addition, contains a xathorhodopsin gene. No CO2-fixation pathways were found.
Adjuvants and Vaccines Used in Allergen-Specific Immunotherapy Induce Neutrophil Extracellular Traps

Aluminum hydroxide (alum) and monophosphoryl-lipid A (MPLA) are conventional adjuvants in vaccines for allergen-specific immunotherapy (AIT). Alum triggers the release of neutrophil extracellular traps (NETs) by neutrophils. NETs contain expelled decondensed chromatin associated with granular material and may act as danger-associated molecular patterns and activate antigen-presenting cells. We investigated whether adjuvant-induced NETs contribute to innate responses to AIT-vaccines. Human neutrophils were incubated with alum, MPLA and adjuvant-containing AIT-vaccine preparations. NETs were verified by time-lapse and confocal fluorescence microscopy and quantitatively assessed by DNA and elastase release and ROS production. In contrast to MPLA, alum represented a potent trigger for NET release. Vaccine formulations containing alum resulted in less NET release than alum alone, whereas the vaccine containing MPLA induced stronger NET responses than MPLA alone. NETs and alum alone and synergistically increased the expression of molecules involved in antigen presentation, i.e., CD80, CD86 and CD83, by peripheral blood monocytes. Monocyte priming with NETs resulted in individually differing IL-1β- and IL-6-responses. Thus, NETs induced by adjuvants in AIT-vaccines can provide autonomous and cooperative effects on early innate responses. The high diversity of individual innate responses to adjuvants and AIT-vaccines may affect their therapeutic efficacy.
β-Cyclodextrin-Based Nanosponges Functionalized with Drugs and Gold Nanoparticles

Drugs are widely used as therapeutic agents; however, they may present some limitations. To overcome some of the therapeutic disadvantages of drugs, the use of β-cyclodextrin-based nanosponges (βCDNS) constitutes a promising strategy. βCDNS are matrices that contain multiple hydrophobic cavities, increasing the loading capacity, association, and stability of the included drugs. On the other hand, gold nanoparticles (AuNPs) are also used as therapeutic and diagnostic agents due to their unique properties and high chemical reactivity. In this work, we developed a new nanomaterial based on βCDNS and two therapeutic agents, drugs and AuNPs. First, the drugs phenylethylamine (PhEA) and 2-amino-4-(4-chlorophenyl)-thiazole (AT) were loaded on βCDNS. Later, the βCDNS–drug supramolecular complexes were functionalized with AuNPs, forming the βCDNS–PhEA–AuNP and βCDNS–AT–AuNP systems. The success of the formation of βCDNS and the loading of PhEA, AT, and AuNPs was demonstrated using different characterization techniques. The loading capacities of PhEA and AT in βCDNS were 90% and 150%, respectively, which is eight times higher than that with native βCD. The functional groups SH and NH2 of the drugs remained exposed and allowed the stabilization of the AuNPs, 85% of which were immobilized. These unique systems can be versatile materials with an efficient loading capacity for potential applications in the transport of therapeutic agents.