Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuron-Glia-Immune Triad and Cortico-Limbic System in Pathology of Pain

Pain is an unpleasant sensation that alerts one to the presence of obnoxious stimuli or sensations. These stimuli are transferred by sensory neurons to the dorsal root ganglia-spinal cord and finally to the brain. Glial cells in the peripheral nervous system, astrocytes in the brain, dorsal root ganglia, and immune cells all contribute to the development, maintenance, and resolution of pain. Both innate and adaptive immune responses modulate pain perception and behavior. Neutrophils, microglial, and T cell activation, essential components of the innate and adaptive immune responses, can play both excitatory and inhibitory roles and are involved in the transition from acute to chronic pain. Immune responses may also exacerbate pain perception by modulating the function of the cortical-limbic brain regions involved in behavioral and emotional responses. The link between an emotional state and pain perception is larger than what is widely acknowledged. In positive psychological states, perception of pain along with other somatic symptoms decreases, whereas in negative psychological states, these symptoms may worsen. Sex differences in mechanisms of pain perception are not well studied. In this review, we highlight what is known, controversies, and the gaps in this field.
The Influence of Drug–Polymer Solubility on Laser-Induced In Situ Drug Amorphization Using Photothermal Plasmonic Nanoparticles

In this study, laser-induced in situ amorphization (i.e., amorphization inside the final dosage form) of the model drug celecoxib (CCX) with six different polymers was investigated. The drug–polymer combinations were studied with regard to the influence of (i) the physicochemical properties of the polymer, e.g., the glass transition temperature (Tg) and (ii) the drug–polymer solubility on the rate and degree of in situ drug amorphization. Compacts were prepared containing 30 wt% CCX, 69.25 wt% polymer, 0.5 wt% lubricant, and 0.25 wt% plasmonic nanoparticles (PNs) and exposed to near-infrared laser radiation. Upon exposure to laser radiation, the PNs generated heat, which allowed drug dissolution into the polymer at temperatures above its Tg, yielding an amorphous solid dispersion. It was found that in situ drug amorphization was possible for drug–polymer combinations, where the temperature reached during exposure to laser radiation was above the onset temperature for a dissolution process of the drug into the polymer, i.e., TDStart. The findings of this study showed that the concept of laser-induced in situ drug amorphization is applicable to a range of polymers if the drug is soluble in the polymer and temperatures during the process are above TDStart.
The Influence of Internal Packaging (Liners) on Moisture Dynamics and Physical and Physiological Quality of Pomegranate Fruit during Cold Storage

Weight loss and decay are common physiological disorders during postharvest handling and storage of pomegranates. The study focused on relating the ability of plastic liners as internal packaging to modify both gaseous and moisture atmosphere around the fruit to moisture dynamics and physical and physiological quality of pomegranate fruit (cv. Wonderful) during storage. Fruit were packed with no-liner, non-perforated ‘Decco’, non-perforated ‘Zoe’, micro-perforated Xtend®, 2 mm macro-perforated high density polyethylene (HDPE), and 4 mm macro-perforated HDPE plastic liners. After 84 days of storage at 5 °C and 90–95% relative humidity (RH), fruit packed with no-liner lost 15.6 ± 0.3% of initial weight. Non-perforated (Decco and Zoe) liners minimised losses to 0.79 and 0.82% compared to Xtend® micro-perforated (4.17%) and 2 mm HDPE (2.44%) and 4 mm macro-perforated HDPE (4.17%) liners, respectively. Clearly, micro- and macro-perforation of liners minimised moisture condensation, fruit decay, and shrivel severity. Micro-perforated Xtend® and macro-perforated 4 mm HDPE were the best treatments in minimising postharvest losses that are often associated with inadequate environment control inside packaging compared to the use of non-perforated liners.
Kinase Inhibitors of DNA-PK, ATM and ATR in Combination with Ionizing Radiation Can Increase Tumor Cell Death in HNSCC Cells While Sparing Normal Tissue Cells

(1) Kinase inhibitors (KI) targeting components of the DNA damage repair pathway are a promising new type of drug. Combining them with ionizing radiation therapy (IR), which is commonly used for treatment of head and neck tumors, could improve tumor control, but could also increase negative side effects on surrounding normal tissue. (2) The effect of KI of the DDR (ATMi: AZD0156; ATRi: VE-822, dual DNA-PKi/mTORi: CC-115) in combination with IR on HPV-positive and HPV-negative HNSCC and healthy skin cells was analyzed. Cell death and cell cycle arrest were determined using flow cytometry. Additionally, clonogenic survival and migration were analyzed. (3) Studied HNSCC cell lines reacted differently to DDRi. An increase in cell death for all of the malignant cells could be observed when combining IR and KI. Healthy fibroblasts were not affected by simultaneous treatment. Migration was partially impaired. Influence on the cell cycle varied between the cell lines and inhibitors; (4) In conclusion, a combination of DDRi with IR could be feasible for patients with HNSCC. Side effects on healthy cells are expected to be limited to normal radiation-induced response. Formation of metastases could be decreased because cell migration is impaired partially. The treatment outcome for HPV-negative tumors tends to be improved by combined treatment.
Hyperalphalipoproteinemia and Beyond: The Role of HDL in Cardiovascular Diseases

Hyperalphalipoproteinemia (HALP) is a lipid disorder characterized by elevated plasma high-density lipoprotein cholesterol (HDL-C) levels above the 90th percentile of the distribution of HDL-C values in the general population. Secondary non-genetic factors such as drugs, pregnancy, alcohol intake, and liver diseases might induce HDL increases. Primary forms of HALP are caused by mutations in the genes coding for cholesteryl ester transfer protein (CETP), hepatic lipase (HL), apolipoprotein C-III (apo C-III), scavenger receptor class B type I (SR-BI) and endothelial lipase (EL). However, in the last decades, genome-wide association studies (GWAS) have also suggested a polygenic inheritance of hyperalphalipoproteinemia. Epidemiological studies have suggested that HDL-C is inversely correlated with cardiovascular (CV) risk, but recent Mendelian randomization data have shown a lack of atheroprotective causal effects of HDL-C. This review will focus on primary forms of HALP, the role of polygenic inheritance on HDL-C, associated risk for cardiovascular diseases and possible treatment options.
On the Inhibitability of Natural Products Isolated from Tetradium ruticarpum towards Tyrosine Phosphatase 1B (PTP1B) and α-Glucosidase (3W37): An In Vitro and In Silico Study

Folk experiences suggest natural products in Tetradium ruticarpum can be effective inhibitors towards diabetes-related enzymes. The compounds were experimentally isolated, structurally elucidated, and tested in vitro for their inhibition effects on tyrosine phosphatase 1B (PTP1B) and α-glucosidase (3W37). Density functional theory and molecular docking techniques were utilized as computational methods to predict the stability of the ligands and simulate interaction between the studied inhibitory agents and the targeted proteins. Structural elucidation identifies two natural products: 2-heptyl-1-methylquinolin-4-one (1) and 3-[4-(4-methylhydroxy-2-butenyloxy)-phenyl]-2-propenol (2). In vitro study shows that the compounds (1 and 2) possess high potentiality for the inhibition of PTP1B (IC50 values of 24.3 ± 0.8, and 47.7 ± 1.1 μM) and α-glucosidase (IC50 values of 92.1 ± 0.8, and 167.4 ± 0.4 μM). DS values and the number of interactions obtained from docking simulation highly correlate with the experimental results yielded. Furthermore, in-depth analyses of the structure–activity relationship suggest significant contributions of amino acids Arg254 and Arg676 to the conformational distortion of PTP1B and 3W37 structures overall, thus leading to the deterioration of their enzymatic activity observed in assay-based experiments. This study encourages further investigations either to develop appropriate alternatives for diabetes treatment or to verify the role of amino acids Arg254 and Arg676.
Dendrimer-Coated Gold Nanoparticles for Efficient Folate-Targeted mRNA Delivery In Vitro

Messenger RNA (mRNA) is not an attractive candidate for gene therapy due to its instability and has therefore received little attention. Recent studies show the advantage of mRNA over DNA, especially in cancer immunotherapy and vaccine development. This study aimed to formulate folic-acid-(FA)-modified, poly-amidoamine-generation-5 (PAMAM G5D)-grafted gold nanoparticles (AuNPs) and to evaluate their cytotoxicity and transgene expression using the luciferase reporter gene (FLuc-mRNA) in vitro. Nanocomplexes were spherical and of favorable size. Nanocomplexes at optimum nanoparticle:mRNA (w/w) binding ratios showed good protection of the bound mRNA against nucleases and were well tolerated in all cell lines. Transgene expression was significantly (p < 0.0001) higher with FA-targeted, dendrimer-grafted AuNPs (Au:G5D:FA) in FA receptors overexpressing MCF-7 and KB cells compared to the G5D and G5D:FA NPs, decreasing significantly (p < 0.01) in the presence of excess competing FA ligand, which confirmed nanocomplex uptake via receptor mediation. Overall, transgene expression of the Au:G5D and Au:G5D:FA nanocomplexes exceeded that of G5D and G5D:FA nanocomplexes, indicating the pivotal role played by the inclusion of the AuNP delivery system. The favorable properties imparted by the AuNPs potentiated an increased level of luciferase gene expression.
First Dose of the BNT162b2 mRNA COVID-19 Vaccine Reduces Symptom Duration and Viral Clearance in Healthcare Workers

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than one hundred million people since the beginning of the worldwide pandemic. In this study, data from a large hospital in central Italy was used to evaluate the impact of the first dose of the BNT162b2 mRNA vaccine on SARS-CoV-2 infections in terms of the prevalence of symptomatic cases, symptom duration, and viral clearance timing. All vaccinated Healthcare Workers (HCWs) with positive RT-PCR by nasopharyngeal (NP) swabs were divided into two cohorts (positive RT-PCR within day 12 and positive RT-PCR between day 13 and day 21 after first dose administration) and compared for the presence and duration of symptoms and the timing of viral clearance. The same variables were evaluated across HCWs with positive RT-PCR within 6 days after first dose administration and non-vaccinated HCWs with positive RT-PCR between 1 October 2020 and 28 February 2021. Eighteen HCWs tested positive on RT-PCR by NP swab from day 1 to day 12 after the 1st dose administration (incidence rate 6.2 × 10−4) and 5 HCWs from day 13 to day 21 (incidence rate 2.3 × 10−4). Symptom duration and viral clearance timing are significantly shorter in the cohort of HCWs with positive RT-PCR 12 days after the first dose of the BNT162b2 mRNA vaccine. The administration of the first dose proved effective in reducing presence, symptom duration, and viral clearance even in HCWs vaccinated for less than 6 days. These results could have implications on public health and post-exposure prophylaxis.
Trace Amine-Associated Receptor 1 Trafficking to Cilia of Thyroid Epithelial Cells

Trace amine-associated receptor 1 (rodent Taar1/human TAAR1) is a G protein-coupled receptor that is mainly recognized for its functions in neuromodulation. Previous in vitro studies suggested that Taar1 may signal from intracellular compartments. However, we have shown Taar1 to localize apically and on ciliary extensions in rodent thyrocytes, suggesting that at least in the thyroid, Taar1 may signal from the cilia at the apical plasma membrane domain of thyrocytes in situ, where it is exposed to the content of the follicle lumen containing putative Taar1 ligands. This study was designed to explore mouse Taar1 (mTaar1) trafficking, heterologously expressed in human and rat thyroid cell lines in order to establish an in vitro system in which Taar1 signaling from the cell surface can be studied in future. The results showed that chimeric mTaar1-EGFP traffics to the apical cell surface and localizes particularly to spherical structures of polarized thyroid cells, procilia, and primary cilia upon serum-starvation. Moreover, mTaar1-EGFP appears to form high molecular mass forms, possibly homodimers and tetramers, in stably expressing human thyroid cell lines. However, only monomeric mTaar1-EGFP was cell surface biotinylated in polarized human thyrocytes. In polarized rat thyrocytes, mTaar1-EGFP is retained in the endoplasmic reticulum, while cilia were reached by mTaar1-EGFP transiently co-expressed in combination with an HA-tagged construct of the related mTaar5. We conclude that Taar1 trafficking to cilia depends on their integrity. The results further suggest that an in vitro cell model was established that recapitulates Taar1 trafficking in thyrocytes in situ, in principle, and will enable studying Taar1 signaling in future, thus extending our general understanding of its potential significance for thyroid autoregulation.
Neurodegeneration in Niemann–Pick Type C Disease: An Updated Review on Pharmacological and Non-Pharmacological Approaches to Counteract Brain and Cognitive Impairment

Niemann–Pick type C (NPC) disease is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol in the late endo-lysosomal system of cells. Progressive neurological deterioration and the onset of symptoms, such as ataxia, seizures, cognitive decline, and severe dementia, are pathognomonic features of the disease. In addition, different pathological similarities, including degeneration of hippocampal and cortical neurons, hyperphosphorylated tau, and neurofibrillary tangle formation, have been identified between NPC disease and other neurodegenerative pathologies. However, the underlying pathophysiological mechanisms are not yet well understood, and even a real cure to counteract neurodegeneration has not been identified. Therefore, the combination of current pharmacological therapies, represented by miglustat and cyclodextrin, and non-pharmacological approaches, such as physical exercise and appropriate diet, could represent a strategy to improve the quality of life of NPC patients. Based on this evidence, in our review we focused on the neurodegenerative aspects of NPC disease, summarizing the current knowledge on the molecular and biochemical mechanisms responsible for cognitive impairment, and suggesting physical exercise and nutritional treatments as additional non-pharmacologic approaches to reduce the progression and neurodegenerative course of NPC disease.
Balancing the CD38 Expression on Effector and Target Cells in Daratumumab-Mediated NK Cell ADCC against Multiple Myeloma

Simple Summary We tracked the cytotoxic potential of NK cells towards multiple myeloma cells in daratumumab-mediated antibody-dependent cellular cytotoxicity assays. These cytotoxicity levels could be directly correlated to the expression of the target antigen (CD38) and to the percentage of fratricide between effector cells. Increasing the expression of CD38 on target cells or neutralizing CD38 on effector cells changed the equilibrium between target and effector cell lysis and promoted multiple myeloma cell death. This study highlights the importance of a balanced CD38 expression on target and effector cells and attempts to alter this balance will affect the susceptibility of MM cells towards daratumumab-mediated cellular toxicity. Abstract Multiple myeloma (MM) is an incurable cancer characterized by the proliferation and accumulation of monoclonal plasma cells in the bone marrow. The monoclonal anti-CD38 daratumumab has taken a central place in the different treatment regimens for newly diagnosed and relapsed, refractory myeloma. In this study, we correlated the NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and potential fratricide induced by daratumumab with CD38-expression levels on both effector and target cells. We show that CD38 expression can be modulated by adding all-trans retinoic acid (ATRA) or interferon-α to MM cells to further fine-tune these effects. In addition, we observed that ADCC becomes inefficient when fratricide occurs and both ADCC and fratricide depend on the balance between CD38 expression on effector and target cells. However, the addition of adjuvants (retinoic acid or interferon-α) to myeloma cells or the inhibition of fratricide using a CD38-blocking nanobody on NK-cells can reverse this balance towards ADCC and thus promote lysis of target cells by ADCC. ATRA and interferon-α increased the CD38 expression at the surface of MM cells about three-fold and two-fold, respectively. This increase was of interest for MM cells with low CD38 expression, that became susceptible to daratumumab-mediated ADCC after preincubation. A CD38-blocking nanobody prevented the binding of daratumumab to these NK-cells and blunted the fratricidal effect on effector NK cells. In conclusion, our study highlights the importance of a balanced CD38 expression on target and effector cells and attempts to alter this balance will affect the susceptibility of MM cells towards daratumumab-mediated ADCC.
Fast Solution Synthesis of NiO-Gd0.1Ce0.9O1.95 Nanocomposite via Different Approach: Influence of Processing Parameters and Characterizations

The synthesis of the nickel oxide-gadolinium doped ceria (NiO-GDC with 65:35 wt. %) nanocomposite powders with a stoichiometry of Gd0.1Ce0. 9O1.95 was performed via fast solution combustion technique; using three different mixing methods: (i) CM (metal cations in an aqueous solution), (ii) HM (hand mortar), and (iii) BM (ball milling). The nanocomposite powders were calcined at 700 °C for 2 h and characterized by Transmission Electron Microscopy (TEM), X-ray fluorescence (XRF), and X-ray Diffraction XRD. The TEM and XRD analyses evidenced the well-dispersed NiO and GDC crystallites with the absence of secondary phases, respectively. Later, the calcined powders (NiO-GDC nanocomposites) were compacted and sintered at 1500 °C for 2 h. The microhardness of the sintered nanocomposites varies in accordance with the synthesis approach: a higher microhardness of 6.04 GPa was obtained for nanocomposites synthesized through CM, while 5.94 and 5.41 GPa were obtained for ball-milling and hand-mortar approach, respectively. Furthermore, it was observed that regardless of the long time-consuming ball-milling process with respect to the hand mortar, there was no significant improvement in the electrical properties.
Flow Characteristics, Mechanical, Thermal, and Thermomechanical Properties, and 3D Printability of Biodegradable Polylactide Containing Boehmite at Different Loadings

This work investigates the effects of modification of polylactide (PLA) using dicumyl peroxide (DCP) as a crosslinker and Joncryl as a chain extender on boehmite distribution. The PLA/boehmite (PLA/BA) composites at various concentrations were prepared via a twin-screw extruder. Transmission electron microscopy showed more agglomerations of BA particles when Joncryl and DCP were added individually to the PLA matrix, with lesser agglomeration upon simultaneous addition of DCP and Joncryl, which led to an enhancement of 10.7% of the heat distortion temperature and 8.8% of the modulus. The existence of fine dispersed BA particles in the BA3 sample improved the cold crystallization by 4 °C. Moreover, the maximum reinforcing effect in increasing the storage modulus of the prepared system was observed upon concurrent addition of DCP and Joncryl, with minimum reinforcing effect upon individual addition of DCP and Joncryl. In general, a bio-based PLA composite base BA with enhanced properties was successfully prepared for various applications.
The Role of Dishware Size in the Perception of Portion Size in Children and Adolescents with Obesity

Purpose: The influence of dishware on portion size perception in children and adolescents is inconclusive. This study investigated how children and adolescents with both obesity and a normal weight perceived portion size in different sized and shaped dishware items. Methods: The study included 60 children and adolescents with overweight and obesity (OBE) and 27 children and adolescents with normal weight (NW) aged from 9 to 17 years. The participants estimated quantities in three pairs of drinking glasses, one pair of bowls and two pairs of plates which varied in size and shape. The children were instructed to state intuitively which portion they would choose for big or small thirst/hunger. Thereafter they were asked to determine the exact amount by answering which dishware item contained the larger/smaller portion (cognitive evaluation). Results: There were no substantial differences in the intuitive evaluation of portion sizes between OBE and NW. During the cognitive evaluation, OBE estimated the amount of water in the glasses more correctly compared to NW (61% vs. 43%; p = 0.008); OBE estimated the amount of lentils in the bowls and on the plates significantly less correctly (39%) compared to NW (56%; p = 0.013). Conclusions: Habit formation and environmental stimuli might play a greater role in estimating food amounts in dishware than the child’s and adolescent’s body weight.
Health Literacy, Health Behavior and States of Health among Trainee Personnel in Northern Germany

(1) Background: The start of vocational education is a challenge for many people whose careers are just beginning. The working conditions exact new physical and mental tolls that can have an impact on their state of health and health behavior. Well-developed health literacy helps to encourage greater self-responsibility with respect to health and safety in the workplace. This study aimed to contribute to the evolution of health-related interventions in vocational training and instruction. (2) Methodology: This cross-sectional study examined health literacy, health behavior, and states of health among trainees engaged in work-and-study vocational training in 11 professions at the start of their education courses in northern Germany. The data were collected using a paper and pencil format. (3) Results: The survey was approved by 47 vocational schools (response rate 14%), with 1797 trainees returning their questionnaires (response rate 36%). The average age of the overall cohort was 21, and 70% of the trainees were female. A total of 47% of the participants began their careers with sufficient health literacy; health literacy was problematic in 40% of cases, and inadequate in 13% of cases. Around 50% of trainees exhibited poor dietary regime and risky alcohol intake, while 58% reported having a medical condition that had been previously formally diagnosed. (4) Conclusion: There is a need to provide support for developing a healthier approach to work at the start of vocational training.