Miracle-dz/UniFAR-FTUs huggingface dataset:
Update of P2X receptor properties and their pharmacology: IUPHAR Review 30

The known seven mammalian receptor subunits (P2X1–7) form cationic channels gated by ATP. Three subunits compose a receptor channel. Each subunit is a polypeptide consisting of two transmembrane regions (TM1 and TM2), intracellular N‐ and C‐termini, and a bulky extracellular loop. Crystallization allowed the identification of the 3D structure and gating cycle of P2X receptors. The agonist‐binding pocket is located at the intersection of two neighbouring subunits. In addition to the mammalian P2X receptors, their primitive ligand‐gated counterparts with little structural similarity have also been cloned. Selective agonists for P2X receptor subtypes are not available, but medicinal chemistry supplied a range of subtype‐selective antagonists, as well as positive and negative allosteric modulators. Knockout mice and selective antagonists helped to identify pathological functions due to defective P2X receptors, such as male infertility (P2X1), hearing loss (P2X2), pain/cough (P2X3), neuropathic pain (P2X4), inflammatory bone loss (P2X5), and faulty immune reactions (P2X7).
A FRET-ICT Dual-Modulated Ratiometric Fluorescence Sensor for Monitoring and Bio-Imaging of Cellular Selenocysteine

Since the fluctuation of cellular selenocysteine (Sec) concentration plays an all-important role in the development of numerous human disorders, the real-time fluorescence detection of Sec in living systems has attracted plenty of interest during the past decade. In order to obtain a faster and more sensitive small organic molecule fluorescence sensor for the Sec detection, a new ratiometric fluorescence sensor Q7 was designed based on the fluorescence resonance energy transfer (FRET) strategy with coumarin fluorophore as energy donor and 4-hydroxy naphthalimide fluorophore (with 2,4-dinitrobenzene sulfonate as fluorescence signal quencher and Sec-selective recognition site) as an energy acceptor. The sensor Q7 exhibited only a blue fluorescence signal, and displayed two well distinguished emission bands (blue and green) in the presence of Sec with ∆λ of 68 nm. Moreover, concentrations ranging of quantitative detection of Sec of Q7 was from 0 to 45 μM (limit of detection = 6.9 nM), with rapid ratiometric response, high sensitivity and selectivity capability. Impressively, the results of the living cell imaging test demonstrated Q7 has the potentiality of being an ideal sensor for real-time Sec detection in biosystems.
Older person’s experiences of benefits gained from the support and advice given during preventive home visits

Background Life expectancy is increasing all over the world. To be able to support this positive development, health interventions focusing on promotion and prevention are crucial. Preventive home visits represent one example of a health intervention which addresses both promotion through a supportive dialogue and prevention by giving advice. However, to give support and advice that older persons experience as beneficial, there is a need for more research. Aim The aim of this study was to explore older person’s experiences of the benefits gained from the support and advice given during the preventive home visit. Method Individual semi‐structured interviews were conducted with 13 older persons, median age 77 years old, living at home, who had received a preventive home visit. The interviews were analysed with content analysis. Findings The overarching theme Becoming empowered and recognised as a person was experienced as the major benefit of the support and advice given during the preventive home visit. The support and advice generated conditions for the person to become empowered, by contributing to a feeling of control and preparedness for the future. Furthermore, the support and advice given contributed to a feeling of becoming recognised as a person, as an outcome of the supportive dialogue and the assessment of their health, behaviour and their surrounding environment. Conclusion The support and advice given during the preventive home visit were experienced as person‐centred, and conditions for becoming empowered were created. In order to create a positive outcome from the support and advice given during the preventive home visit, it seems important to focus on providing both a supportive dialogue and a structured assessment.
Drug injection-related norms and high-risk behaviors of people who inject drugs in Athens, Greece.

Drug use involves social interactions. Therefore, norms in the proximal environment of people who inject drugs (PWID) can favor behaviors that may in turn result in HIV transmission. This work aimed at studying drug injection-related norms and their potential association with risky behaviors among PWID in Athens, Greece, in the context of severe economic recession and political activism that followed the fiscal crisis and soon after a recent HIV outbreak had leveled off. The Transmission Reduction Intervention Project (TRIP) was a social network-based approach (June 2013 - July 2015) that involved two groups of PWID seeds - one with recent HIV infection and one with long-term HIV infection - and one control group of HIV-negative PWID. Network contacts of seeds were also enrolled. TRIP participants answered a structured questionnaire that included items on injection-related norms and behaviors. TRIP recruited 320 PWID (HIV positive, 44.4%). TRIP participants, especially those without HIV, often recalled or perceived as normative among their partners and in their networks some behaviors that can lead to HIV transmission. TRIP participants who recalled that they were encouraged by their regular drug partners to use an unclean syringe were almost twice as likely to report that they share syringes [Odds ratio (OR): 2.03 (95% Confidence Interval: 1.86, 2.21), or give syringes to someone else (OR: 1.70; 95% CI: 1.42, 2.04) as those who did not recall such an encouragement. Associations were modified by HIV-status. Further research is needed on the multiple determinants (social, economic, political) of norms in the social environments of PWID. Since peer norms are associated with risky behaviors, interventions should be developed to encourage norms and peer pressure against the sharing of injection equipment.
The Metabolic Effects of Cynara Supplementation in Overweight and Obese Class I Subjects with Newly Detected Impaired Fasting Glycemia: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Impaired fasting glucose (IFG) is a condition that precedes diabetes and increases the risk of developing it. Studies support the hypoglycemic effect of Cynara scolymus (Cs) extracts due to the content of chlorogenic acid, which is a potent inhibitor of glucose 6-phosphate translocase and of dicaffeoylquinic acid derivatives that modulate the activity of alpha-glucosidase. Given this background, we investigated whether a new highly standardized Cs extract could improve glycemic control, insulin sensitivity and other metabolic parameters (total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) Triglycerides, Apolipo protein B (ApoB), Apolipo protein A (ApoA), waist circumference, visceral adipose tissue (VAT) by dual-energy X-ray absorptiometry (DXA) in overweight subjects with newly diagnosed IFG. Fifty-four subjects (females/males 26/28, mean ± SD age 51.5 ± 6.2) were randomly assigned to the supplemented group (n = 27) and placebo (n = 27). After multiple testing correction, statistically significant interactions between time and group were observed for the primary endpoint glycemia (β = 0.36, p < 0.0001) and for the secondary endpoints HDL (β = −0.10, p < 0.0001), total cholesterol/HDL (β = 0.27, p < 0.0001), LDL (β = 0.15, p = 0.005), LDL/HDL (β = 0.23, p = 0.001), insulin (β = 1.28, p = 0.04), glycated hemoglobin (β = 0.21, p = 0.0002), A1c-derived average glucose (β = 0.34, p = 0.0002), ApoB (β = 6.00, p = 0.01), ApoA (β = −4.50, p = 0.04), ApoB/ApoA (β = 0.08, p = 0.003), waist circumference (β = 1.89, p = 0.05), VATβ = 222.37, p = 0.005). In conclusion, these results confirm that Cs supplementation has a significant effect on metabolic parameters in IFG patients.
Regulation and functions of the RhoA regulatory guanine nucleotide exchange factor GEF-H1

ABSTRACT Since the discovery by Madaule and Axel in 1985 of the first Ras homologue (Rho) protein in Aplysia and its human orthologue RhoB, membership in the Rho GTPase family has grown to 20 proteins, with representatives in all eukaryotic species. These GTPases are molecular switches that cycle between active (GTP bound) and inactivate (GDP bound) states. The exchange of GDP for GTP on Rho GTPases is facilitated by guanine exchange factors (GEFs). Approximately 80 Rho GEFs have been identified to date, and only a few GEFs associate with microtubules. The guanine nucleotide exchange factor H1, GEF-H1, is a unique GEF that associates with microtubules and is regulated by the polymerization state of microtubule networks. This review summarizes the regulation and functions of GEF-H1 and discusses the roles of GEF-H1 in human diseases.
Antitumor, Immunomodulatory and Antiangiogenic Efficacy of Medicinal Mushroom Extract Mixtures in Advanced Colorectal Cancer Animal Model

Due to frequent drug resistance and/or unwanted side-effects during conventional and targeted cancer treatments, development of multi-target therapies is an important research field. Medicinal mushrooms’ isolated specific compounds and mushroom extracts have been already proven as non-toxic multi-target inhibitors of specific oncogenic pathways, as well as potent immunomodulators. However, research on antitumor effects of multiple-species extract mixtures was limited so far. The aim of this study was therefore, a study of medicinal mushroom preparations AGARIKON.1 and AGARIKON PLUS on colorectal cell lines in vitro and colorectal mice model in vivo. We found a significant antiproliferative and pro-apoptotic effect of tested medicinal mushroom preparations on colorectal (HCT-116, SW620) tumor cell lines, while the effect on human fibroblast cell line (WI-38) was proliferative emphasizing a specificity towards tumor cell lines. We further investigated the effect of the medicinal mushroom preparations AGARIKON.1 and AGARIKON PLUS in various combinations with conventional cytostatic drug 5-fluorouracil in the advanced metastatic colorectal cancer mouse model CT26.WT. AGARIKON.1 and AGARIKON PLUS exhibited immunostimulatory and antiangiogenic properties in vivo which resulted in significantly increased survival and reduction in tumor volume. The antitumor effects of AGARIKON.1 and AGARIKON PLUS, with or without 5-fluorouracil, are based on M1 macrophage polarization enhancement, inhibition of M2 and tumor-associated macrophage (TAM) polarization, effects on T helper cell Th1/Th2/Th17 cytokine profiles, direct inhibition of CT26.WT tumor growth, inhibition of vascular endothelial growth factors (VEGF) and metalloproteinases 2 and 9 (MMP-2 and MMP-9) modulation. The administration of AGARIKON.1 and AGARIKON PLUS did not show genotoxic effect. This data provides good basis for an expanded translational study.
Structure, mechanism, and regulation of mitochondrial DNA transcription initiation

Mitochondria are specialized compartments that produce requisite ATP to fuel cellular functions and serve as centers of metabolite processing, cellular signaling, and apoptosis. To accomplish these roles, mitochondria rely on the genetic information in their small genome (mitochondrial DNA) and the nucleus. A growing appreciation for mitochondria's role in a myriad of human diseases, including inherited genetic disorders, degenerative diseases, inflammation, and cancer, has fueled the study of biochemical mechanisms that control mitochondrial function. The mitochondrial transcriptional machinery is different from nuclear machinery. The in vitro re-constituted transcriptional complexes of Saccharomyces cerevisiae (yeast) and humans, aided with high-resolution structures and biochemical characterizations, have provided a deeper understanding of the mechanism and regulation of mitochondrial DNA transcription. In this review, we will discuss recent advances in the structure and mechanism of mitochondrial transcription initiation. We will follow up with recent discoveries and formative findings regarding the regulatory events that control mitochondrial DNA transcription, focusing on those involved in cross-talk between the mitochondria and nucleus.
Trial of Rivaroxaban in AntiPhospholipid Syndrome (TRAPS): Two‐year outcomes after the study closure

Trial of Rivaroxaban in AntiPhospholipid Syndrome was a prospective randomized, open‐label, noninferiority study conducted in 14 centers in Italy. Rivaroxaban was compared with warfarin for the prevention of thromboembolic events, major bleeding, and vascular death in high‐risk, triple‐positive patients with antiphospholipid syndrome.
Development of improved sampling and analysis methods for measuring organic, elemental, and water-soluble organic carbon in atmospheric aerosols and application to aerosol studies in Europe and tropical/equatorial and oceanic regions

The work conducted in this thesis had the following objectives: (1) to develop improved methods for a better discrimination between organic and elemental carbon (OC and EC) using the thermal-optical transmission (TOT) technique; (2) to deploy improved collection procedures for carbonaceous aerosols, whereby the sampling artifacts are better controlled or can be corrected for; (3) to perform detailed carbonaceous aerosol characterisation studies in Belgium and at urban and forested sites throughout Europe and (4) in the Brazilian Amazon basin, the tropical Atlantic Ocean, and at Amsterdam Island in the Indian Ocean. With regard to objective (1), the OC/EC split in three different temperature programs was examined for samples from widely different origins. This study confirmed that the OC/EC split in TOT depends upon the temperature program used, particularly that in the first phase of the analysis (in pure He). As to objective (2), a denuded sampling setup (with upstream of the filter holder with two quartz fibre filters a denuder for volatile organic compounds and oxidising inorganic gases) and the tandem filter method (with two quartz fibre filters in series without denuder) were used in parallel for low-volume PM2.5 collections in several campaigns since 2002. It was found that subtracting the back filter OC from the front filter OC yields “artifact-free” particulate OC data. With regard to objective (3), the median PM2.5 EC concentrations at our various sites in Europe ranged from 0.07 μg/m3 in the 2007 campaign at Hyytiala, Finland, to 3.3 μg/m3 during the 2002 campaign at a kerbside site in Budapest. There was a general increasing trend for EC levels from forested sites, to urban sites, and to kerbside sites, reflecting the increasing impact of local anthropogenic emissions, especially those from traffic. For OC, however, there was no clear spatial trend. As to objective (4), the OC and EC data from a 2006 oceanic cruise in the northern hemisphere contrasted substantially with those found for Amsterdam Island. At the latter site, EC was below the detection limit (of 10 ng/m3) and total OC was around a factor of 4 lower than during the northern hemisphere cruise.
The Effects of Resistance Training on Blood Pressure in Preadolescents and Adolescents: A Systematic Review and Meta-Analysis

The aim was to systematically review and meta-analyze the current evidence for the effects of resistance training (RT) on blood pressure (BP) as the main outcome and body mass index (BMI) in children and adolescents. Two authors systematically searched the PubMed, SPORTDiscus, Web of Science Core Collection and EMBASE electronic databases. Inclusion criteria were: (1) children and adolescents (aged 8 to 18 years); (2) intervention studies including RT and (3) outcome measures of BP and BMI. The selected studies were analyzed using the Cochrane Risk-of-Bias Tool. Eight articles met inclusion criteria totaling 571 participants. The mean age ranged from 9.3 to 15.9 years and the mean BMI of 29.34 (7.24) kg/m2). Meta-analysis indicated that RT reduced BMI significantly (mean difference (MD): −0.43 kg/m2 (95% CI: −0.82, −0.03), P = 0.03; I2 = 5%) and a non-significant decrease in systolic BP (SBP) (MD: −1.09 mmHg (95% CI: −3.24, 1.07), P = 0.32; I2 = 67%) and diastolic BP (DBP) (MD: −0.93 mmHg (95% CI: −2.05, 0.19), P = 0.10; I2 = 37%). Limited evidence suggests that RT has no adverse effects on BP and may positively affect BP in youths. More high-quality studies are needed to clarify the association between RT and BP in light of body composition changes throughout childhood and adolescence.
Characterization of D-17 Canine Osteosarcoma Cell Line and Evaluation of Its Ability to Response to Infective Stressor Used as Alternative Anticancer Therapy

Simple Summary Osteosarcoma (OSA) is the most common primary bone tumor both in dogs and in humans. Canine and human OSA share common characteristics making dogs a good model in comparative oncology. In the last years, in order to reduce animal testing, researchers shifted their attention to in vitro studies using cell lines. Aim of this work is to understand if cells obtained from canine metastatic pulmonary OSA can be a good model for cancer studies, both in humans and dogs. Results of this study were obtained by: the characterization of the expression of genes involved in the innate immune response, the sequencing of a single gene with a key role in immune response and the evaluation of the capacity of these cells to interact with microorganisms that can be used as alternative anticancer therapies. Obtained data were in agreement with those reported in literature regarding the expression of genes both in spontaneous tumors and in vitro cell lines. So, they confirmed the maintenance of cell line D-17 of the pulmonary metastatic OSA characteristics. The selected cells also demonstrated the ability to interact with the microorganism, this suggests that they may be a possible model for the preliminary evaluation of new therapeutic approaches based on the use of bacteria. Abstract Osteosarcoma (OSA) is a rare cancer both in human and dog although the incidence rate in dogs is 27 times higher than in human. Many studies employed D-17 as cell line for in vitro test to evaluate conventional anticancer therapies; however, little is known about D-17 cell line. The aim of our study was to evaluate the basal level of gene expression of pivotal molecules in the innate immune response and cell cycle regulation and to establish the ability of this cell line to react to Salmonella typhimurium (ST) infective stressor. IL15, IL10, iNOS, TLR5, CD14, PTEN and IL18 were expressed in an inconsistent manner among experiments. The other genes under study were expressed in all samples. ST showed ability to penetrate D-17 causing pro-inflammatory response. Our results outline the expression in D-17 of important genes involved in innate immune response. These results provide important data on D-17 basal gene expression profile useful for in vitro preliminary evaluation of new therapeutic approaches.
Thaumatin-like proteins and a cysteine protease inhibitor secreted by the pine wood nematode Bursaphelenchus xylophilus induce cell death in Nicotiana benthamiana

Pine wilt disease (PWD) is an infectious disease of pines that typically kills affected trees. The causal pathogen of PWD is the pine wood nematode (PWN), Bursaphelenchus xylophilus. Understanding of the disease has advanced in recent years through the use of a highly sensitive proteomics procedure and whole genome sequence analysis; in combination, these approaches have enabled identification of proteins secreted by PWNs. However, the roles of these proteins during the onset of parasitism have not yet been elucidated. In this study, we used a leaf-disk assay based on transient overexpression in Nicotiana benthamiana to allow functional screening of 10 candidate pathogenic proteins secreted by PWNs. These proteins were selected based on previous secretome and RNA-seq analyses. We found that five molecules induced significant cell death in tobacco plants relative to a GFP-only control. Three of these proteins (Bx-TH1, Bx-TH2, and Bx-CPI) may have a role in molecular mimicry and likely make important contributions to inducing hypersensitive responses in host plants.
Point-of-Care Testing for Pharyngitis in the Pharmacy

Pharyngitis (also known as sore throat) is a common, predominately viral, self-limiting condition which can be symptomatically managed without antibiotic treatment. Inappropriate antibiotic use for pharyngitis contributes to the development and spread of antibiotic resistance. However, a small proportion of sore throats caused by group A streptococcal (GAS) infection may benefit from the provision of antibiotics. Establishing the cause of infection is therefore an important step in effective antibiotic stewardship. Point-of-care (POC) tests, where results are available within minutes, can distinguish between viral and GAS pharyngitis and can therefore guide treatment in primary healthcare settings such as community pharmacies, which are often the first point of contact with the healthcare system. In this opinion article, the evidence for the use of POC testing in the community pharmacy has been discussed. Evidence suggests that pharmacy POC testing can promote appropriate antibiotic use and reduce the need for general practitioner consultations. Challenges to implementation include cost, training and ‘who prescribes’, with country and regional differences presenting a particular issue. Despite these challenges, POC testing for pharyngitis has become widely available in pharmacies in some countries and may represent a strategy to contain antibiotic resistance and contribute to antimicrobial stewardship.
Lactic Acid Bacteria Ameliorate Diesel Exhaust Particulate Matter-Exacerbated Allergic Inflammation in a Murine Model of Asthma

Several air pollution components such as sulfur dioxide, ozone, nitrogen dioxide, and diesel exhaust particulate matter (DEPM) have been linked to the development of asthma. In this study, we investigated the therapeutic potential of three lactic acid bacteria species, Lactobacillus plantarum GREEN CROSS Wellbeing (GCWB)1001, Pediococcus acidilactici GCWB1085, and Lactobacillus rhamnosus GCWB1156, in preventing DEPM-exacerbated asthma in mice. BALB/c mice were first sensitized with ovalbumin (OVA) and were either challenged with OVA or DEPM (DEPM-exacerbated asthma model) by intranasal instillation. All three strains showed no hemolytic activity, suggesting a good safety profile. Oral administration of lactic acid bacteria reduced OVA + DEPM-induced inflammatory infiltration, goblet cell hyperplasia, airway remodeling, and the levels of proinflammatory cytokines and chemokines in bronchoalveolar lavage fluid (BALF). The probiotics also attenuated OVA + DEPM-induced immunoglobulin E (IgE) levels in serum and in BALF, and significantly reduced caspase-3 activity, total collagen level, and matrix metalloproteinase (MMP)-9 activity. In conclusion, lactic acid bacteria such as L. plantarum GCWB1001, P. acidilactici GCWB1085, and L. rhamnosus treatment in mice with asthma showed significant efficacy in preventing lung inflammation exacerbated by DEPM administration.