bluuebunny/crossref_metadata_2025 huggingface dataset:
Sponge Whirl-Pak Sampling Method and Droplet Digital RT-PCR Assay for Monitoring of SARS-CoV-2 on Surfaces in Public and Working Environments
Authors: Cardinale Davide , Tafuro Maria , Mancusi Andrea , Girardi Santa , Capuano Federico , Proroga Yolande Thérèse Rose , Corrado Federica , D’Auria Jacopo Luigi , Coppola Annachiara , Rofrano Giuseppe , Volzone Palmiero , Galdi Pio , De Vita Sabato , Gallo Alfonso , Suffredini Elisabetta , Pierri Biancamaria , Cerino Pellegrino , Morgante Maria
Published: May 2022

The SARS-CoV-2 can spread directly via saliva, respiratory aerosols and droplets, and indirectly by contact through contaminated objects and/or surfaces and by air. In the context of COVID-19 fomites can be an important vehicle of virus transmission and contribute to infection risk in public environments. The aim of the study was to analyze through surface sampling (sponge method) the presence of SARS-CoV-2 in public and working environments, in order to evaluate the risk for virus transmission. Seventy-seven environmental samples were taken using sterile sponges in 17 animal farms, 4 public transport buses, 1 supermarket and 1 hotel receptive structure. Furthermore, 246 and 93 swab samples were taken in the farms from animals and from workers, respectively. SARS-CoV-2 detection was conducted by real-time RT-PCR and by digital droplet RT-PCR (dd RT-PCR) using RdRp, gene E and gene N as targets. None of the human and animal swab samples were positive for SARS-CoV-2, while detection was achieved in 20 of the 77 sponge samples (26%) using dd RT-PCR. Traces of the RdRp gene, gene E and gene N were found in 17/77 samples (22%, average concentration 31.2 g.c./cm2, range 5.6 to 132 g.c./cm2), 8/77 samples (10%, average concentration 15.1 g.c./cm2, range 6 to 36 g.c./cm2), and in 1/77 (1%, concentration 7.2 g.c./cm2). Higher detection rates were associated with sampling in animal farms and on public transport buses (32% and 30%) compared to the supermarket (21%) and the hotel (no detection). The result of the study suggests that the risk of contamination of surfaces with SARS-CoV-2 increases in environments in which sanitation strategies are not suitable and/or in highly frequented locations, such as public transportation. Considering the analytical methods, the dd RT-PCR was the only approach achieving detection of SARS-CoV-2 traces in environmental samples. Thus, dd RT-PCR emerges as a reliable tool for sensitive SARS-CoV-2 detection.
Effectiveness of a Brief Lifestyle Intervention in the Prenatal Care Setting to Prevent Excessive Gestational Weight Gain and Improve Maternal and Infant Health Outcomes
Authors: Krebs Franziska , Lorenz Laura , Nawabi Farah , Alayli Adrienne , Stock Stephanie
Published: May 2022

Research on perinatal programming shows that excessive gestational weight gain (GWG) increases the risk of overweight and obesity later in a child’s life and contributes to maternal weight retention and elevated risks of obstetrical complications. This study examined the effectiveness of a brief lifestyle intervention in the prenatal care setting, compared to routine prenatal care, in preventing excessive GWG as well as adverse maternal and infant health outcomes. The GeMuKi study was designed as a cluster RCT using a hybrid effectiveness implementation design and was conducted in the prenatal care setting in Germany. A total of 1466 pregnant women were recruited. Pregnant women in intervention regions received up to six brief counseling sessions on lifestyle topics (e.g., physical activity, nutrition, drug use). Data on GWG and maternal and infant outcomes were entered into a digital data platform by the respective healthcare providers. The intervention resulted in a significant reduction in the proportion of women with excessive GWG (OR = 0.76, 95% CI (0.60 to 0.96), p = 0.024). Gestational weight gain in the intervention group was reduced by 1 kg (95% CI (−1.56 to −0.38), p < 0.001). No evidence of intervention effects on pregnancy, birth, or neonatal outcomes was found.
Mortality, Morbidity and Health-Related Outcomes in Informal Caregivers Compared to Non-Caregivers: A Systematic Review
Authors: Janson Patrick , Willeke Kristina , Zaibert Lisa , Budnick Andrea , Berghöfer Anne , Kittel-Schneider Sarah , Heuschmann Peter U. , Zapf Andreas , Wildner Manfred , Stupp Carolin , Keil Thomas
Published: May 2022

A systematic overview of mental and physical disorders of informal caregivers based on population-based studies with good methodological quality is lacking. Therefore, our aim was to systematically summarize mortality, incidence, and prevalence estimates of chronic diseases in informal caregivers compared to non-caregivers. Following PRISMA recommendations, we searched major healthcare databases (CINAHL, MEDLINE and Web of Science) systematically for relevant studies published in the last 10 years (without language restrictions) (PROSPERO registration number: CRD42020200314). We included only observational cross-sectional and cohort studies with low risk of bias (risk scores 0–2 out of max 8) that reported the prevalence, incidence, odds ratio (OR), hazard ratio (HR), mean- or sum-scores for health-related outcomes in informal caregivers and non-caregivers. For a thorough methodological quality assessment, we used a validated checklist. The synthesis of the results was conducted by grouping outcomes. We included 22 studies, which came predominately from the USA and Europe. Informal caregivers had a significantly lower mortality than non-caregivers. Regarding chronic morbidity outcomes, the results from a large longitudinal German health-insurance evaluation showed increased and statistically significant incidences of severe stress, adjustment disorders, depression, diseases of the spine and pain conditions among informal caregivers compared to non-caregivers. In cross-sectional evaluations, informal caregiving seemed to be associated with a higher occurrence of depression and of anxiety (ranging from 4 to 51% and 2 to 38%, respectively), pain, hypertension, diabetes and reduced quality of life. Results from our systematic review suggest that informal caregiving may be associated with several mental and physical disorders. However, these results need to be interpreted with caution, as the cross-sectional studies cannot determine temporal relationships. The lower mortality rates compared to non-caregivers may be due to a healthy-carer bias in longitudinal observational studies; however, these and other potential benefits of informal caregiving deserve further attention by researchers.
China’s Changing Alcohol Market and Need for an Enhanced Policy Response: A Narrative Review
Authors: Liu Shiwei , Huang Fulin , Zhu Xiaolei , Zhou Suhua , Si Xiang , Zhao Yan , Liu Yang , Zhang Xiaochang , Casswell Sally
Published: May 2022

This study describes trends in alcohol consumption in the context of an expanding commercial context, current policy responses, and flaws in relation to international best practice for alcohol control in China. We surveyed the literature and other documents in Chinese or English up to December 2020 on policy responses to alcohol consumption and harm, industry structure, and marketing practices in China. Databases searched included PubMed, China National Knowledge Internet, Wanfang Data, Web of Science, and Baidu Scholar. We also scanned the official websites of government organizations and gathered information using snowballing. We analyzed existing alcohol policy against evidence-based, cost-effective policies for reducing alcohol harm. Our findings show that although some restrictive policies have been enacted with potential impacts on alcohol harm, they are not comprehensive, and some are poorly executed. The long history of alcohol use remains an important element in alcohol consumption by the Chinese population. However, alcohol marketing and promotion, ease of access, and affordability have become increasingly prominent. The gaps identified in alcohol policy suggest improved strategies and measures to reduce the harmful use of alcohol are urgently needed in China.
Lane-Level Regional Risk Prediction of Mainline at Freeway Diverge Area
Authors: Lyu Nengchao , Wen Jiaqiang , Hao Wei
Published: May 2022

Real-time regional risk prediction can play a crucial role in preventing traffic accidents. Thus, this study established a lane-level real-time regional risk prediction model. Based on observed data, the least squares-support vector machines (LS-SVM) algorithm was used to identify each lane region of the mainline, and the initial traffic parameters and surrogate safety measures (SSMs) were extracted and aggregated. The negative samples that characterized normal traffic and the positive samples that characterized regional risk were identified. Mutual information (MI) was used to determine the information gain of various feature variables in the samples, and the key feature variables affecting the regional conditions were tested and screened by means of binary logit regression analysis. Upon screening the variables and corresponding labels, the construction and verification of a lane-level regional risk prediction model was completed using the catastrophe theory. The results showed that lane difference is an important parameter to reduce the uncertainty of regional risk, and its odds ratio (OR) was 16.30 at the 95% confidence level. The 10%-quantile modified time to collision (MTTC) inverse, the speed difference between lanes, and 10%-quantile headway (DHW) had an obvious influence on regional status. The model achieved an overall accuracy of 86.50%, predicting 84.78% of regional risks with a false positive rate of 13.37% and 86.63% of normal traffic with a false positive rate of 15.22%. The proposed model can provide a basis for formulating individualized active traffic control strategies for different lanes.
Exosomal Metabolic Signatures Are Associated with Differential Response to Neoadjuvant Chemotherapy in Patients with Breast Cancer
Authors: Joshi Shriya , Garlapati Chakravarthy , Bhattarai Shristi , Su Yixin , Rios-Colon Leslimar , Deep Gagan , Torres Mylin A. , Aneja Ritu
Published: May 2022

Neoadjuvant chemotherapy (NAC) is commonly used in breast cancer (BC) patients to increase eligibility for breast-conserving surgery. Only 30% of patients with BC show pathologic complete response (pCR) after NAC, and residual disease (RD) is associated with poor long-term prognosis. A critical barrier to improving NAC outcomes in patients with BC is the limited understanding of the mechanisms underlying differential treatment outcomes. In this study, we evaluated the ability of exosomal metabolic profiles to predict NAC response in patients with BC. Exosomes isolated from the plasma of patients after NAC were used for metabolomic analyses to identify exosomal metabolic signatures associated with the NAC response. Among the 16 BC patients who received NAC, eight had a pCR, and eight had RD. Patients with RD had 2.52-fold higher exosome concentration in their plasma than those with pCR and showed significant enrichment of various metabolic pathways, including citrate cycle, urea cycle, porphyrin metabolism, glycolysis, and gluconeogenesis. Additionally, the relative exosomal levels of succinate and lactate were significantly higher in patients with RD than in those with pCR. These data suggest that plasma exosomal metabolic signatures could be associated with differential NAC outcomes in BC patients and provide insight into the metabolic determinants of NAC response in patients with BC.
A 4-Week Diet Low or High in Advanced Glycation Endproducts Has Limited Impact on Gut Microbial Composition in Abdominally Obese Individuals: The deAGEing Trial
Authors: Linkens Armand M. A. , van Best Niels , Niessen Petra M. , Wijckmans Nicole E. G. , de Goei Erica E. C. , Scheijen Jean L. J. M. , van Dongen Martien C. J. M. , van Gool Christel C. J. A. W. , de Vos Willem M. , Houben Alfons J. H. M. , Stehouwer Coen D. A. , Eussen Simone J. M. P. , Penders John , Schalkwijk Casper G.
Published: May 2022

Dietary advanced glycation endproducts (AGEs), abundantly present in Westernized diets, are linked to negative health outcomes, but their impact on the gut microbiota has not yet been well investigated in humans. We investigated the effects of a 4-week isocaloric and macronutrient-matched diet low or high in AGEs on the gut microbial composition of 70 abdominally obese individuals in a double-blind parallel-design randomized controlled trial (NCT03866343). Additionally, we investigated the cross-sectional associations between the habitual intake of dietary dicarbonyls, reactive precursors to AGEs, and the gut microbial composition, as assessed by 16S rRNA amplicon-based sequencing. Despite a marked percentage difference in AGE intake, we observed no differences in microbial richness and the general community structure. Only the Anaerostipes spp. had a relative abundance >0.5% and showed differential abundance (0.5 versus 1.11%; p = 0.028, after low- or high-AGE diet, respectively). While the habitual intake of dicarbonyls was not associated with microbial richness or a general community structure, the intake of 3-deoxyglucosone was especially associated with an abundance of several genera. Thus, a 4-week diet low or high in AGEs has a limited impact on the gut microbial composition of abdominally obese humans, paralleling its previously observed limited biological consequences. The effects of dietary dicarbonyls on the gut microbiota composition deserve further investigation.
Insecticidal Triterpenes in Meliaceae: Plant Species, Molecules, and Activities: Part II (Cipadessa, Melia)
Authors: Lin Meihong , Bi Xiaoyang , Zhou Lijuan , Huang Jiguang
Published: May 2022

Plant-originated triterpenes are important insecticidal molecules. Research on the insecticidal activity of molecules from Meliaceae plants has always been a hotspot due to the molecules from this family showing a variety of insecticidal activities with diverse mechanisms of action. In this paper, we discussed 116 triterpenoid molecules with insecticidal activity from 22 plant species of five genera (Cipadessa, Entandrophragma, Guarea, Khaya, and Melia) in Meliaceae. In these genera, the insecticidal activities of plants from Entandrophragma and Melia have attracted substantial research attention in recent years. Specifically, the insecticidal activities of plants from Melia have been systemically studied for several decades. In total, the 116 insecticidal chemicals consisted of 34 ring-intact limonoids, 31 ring-seco limonoids, 48 rearranged limonoids, and 3 tetracyclic triterpenes. Furthermore, the 34 ring-intact limonoids included 29 trichilin-class chemicals, 3 azadirone-class chemicals, and 1 cedrelone-class and 1 havanensin-class limonoid. The 31 ring-seco limonoids consisted of 16 C-seco group chemicals, 8 B,D-seco group chemicals, 4 A,B-seco group chemicals, and 3 D-seco group chemicals. Furthermore, among the 48 rearranged limonoids, 46 were 2,30-linkage group chemicals and 2 were 10,11-linkage group chemicals. Specifically, the 46 chemicals belonging to the 2,30-linkage group could be subdivided into 24 mexicanolide-class chemicals and 22 phragmalin-class chemicals. Additionally, the three tetracyclic triterpenes were three protolimonoids. To sum up, 80 chemicals isolated from 19 plant species exhibited antifeedant activity toward 14 insect species; 18 chemicals isolated from 17 plant species exhibited poisonous activity toward 10 insect species; 16 chemicals isolated from 11 plant species possessed growth-regulatory activity toward 8 insect species. In particular, toosendanin was the most effective antifeedant and insect growth-regulatory agent. The antifeedant activity of toosendanin was significant. Owing to its high effect, toosendanin has been commercially applied. Three other molecules, 1,3-dicinnamoyl-11-hydroxymeliacarpin, 1-cinnamoyl-3-methacryl-11-hydroxymeliacarpin, and 1-cinnamoyl-3-acetyl-11-hydroxymeliacarpin, isolated from Meliaazedarach, exhibited a highly poisonous effect on Spodoptera littoralis; thus, they deserve further attention.
Iron Mining for Erythropoiesis
Authors: Correnti Margherita , Gammella Elena , Cairo Gaetano , Recalcati Stefania
Published: May 2022

Iron is necessary for essential processes in every cell of the body, but the erythropoietic compartment is a privileged iron consumer. In fact, as a necessary component of hemoglobin and myoglobin, iron assures oxygen distribution; therefore, a considerable amount of iron is required daily for hemoglobin synthesis and erythroid cell proliferation. Therefore, a tight link exists between iron metabolism and erythropoiesis. The liver-derived hormone hepcidin, which controls iron homeostasis via its interaction with the iron exporter ferroportin, coordinates erythropoietic activity and iron homeostasis. When erythropoiesis is enhanced, iron availability to the erythron is mainly ensured by inhibiting hepcidin expression, thereby increasing ferroportin-mediated iron export from both duodenal absorptive cells and reticuloendothelial cells that process old and/or damaged red blood cells. Erythroferrone, a factor produced and secreted by erythroid precursors in response to erythropoietin, has been identified and characterized as a suppressor of hepcidin synthesis to allow iron mobilization and facilitate erythropoiesis.
Basic Science with Preclinical Models to Investigate and Develop Liquid Biopsy: What Are the Available Data and Is It a Fruitful Approach?
Authors: Cena Benedetta , Melloul Emmanuel , Demartines Nicolas , Dormond Olivier , Labgaa Ismail
Published: May 2022

The molecular analysis of circulating analytes (circulating tumor-DNA (ctDNA), -cells (CTCs) and -RNA (ctRNA)/exosomes) deriving from solid tumors and detected in the bloodstream—referred as liquid biopsy—has emerged as one of the most promising concepts in cancer management. Compelling data have evidenced its pivotal contribution and unique polyvalence through multiple applications. These data essentially derived from translational research. Therewith, data on liquid biopsy in basic research with preclinical models are scarce, a concerning lack that has been widely acknowledged in the field. This report aimed to comprehensively review the available data on the topic, for each analyte. Only 17, 17 and 2 studies in basic research investigated ctDNA, CTCs and ctRNA/exosomes, respectively. Albeit rare, these studies displayed noteworthy relevance, demonstrating the capacity to investigate questions related to the biology underlying analytes release that could not be explored via translational research with human samples. Translational, clinical and technological sectors of liquid biopsy may benefit from basic research and should take note of some important findings generated by these studies. Overall, results underscored the need to intensify the efforts to conduct future studies on liquid biopsy in basic research with new preclinical models.
Patients’ Stem Cells Differentiation in a 3D Environment as a Promising Experimental Tool for the Study of Amyotrophic Lateral Sclerosis
Authors: Scarian Eveljn , Bordoni Matteo , Fantini Valentina , Jacchetti Emanuela , Raimondi Manuela Teresa , Diamanti Luca , Carelli Stephana , Cereda Cristina , Pansarasa Orietta
Published: May 2022

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease (NDD) that affects motor neurons, causing weakness, muscle atrophy and spasticity. Unfortunately, there are only symptomatic treatments available. Two important innovations in recent years are three-dimensional (3D) bioprinting and induced pluripotent stem cells (iPSCs). The aim of this work was to demonstrate the robustness of 3D cultures for the differentiation of stem cells for the study of ALS. We reprogrammed healthy and sALS peripheral blood mononuclear cells (PBMCs) in iPSCs and differentiated them in neural stem cells (NSCs) in 2D. NSCs were printed in 3D hydrogel-based constructs and subsequently differentiated first in motor neuron progenitors and finally in motor neurons. Every step of differentiation was tested for cell viability and characterized by confocal microscopy and RT-qPCR. Finally, we tested the electrophysiological characteristics of included NSC34. We found that NSCs maintained good viability during the 3D differentiation. Our results suggest that the hydrogel does not interfere with the correct differentiation process or with the electrophysiological features of the included cells. Such evidence confirmed that 3D bioprinting can be considered a good model for the study of ALS pathogenesis.
Maternal Separation Alters Ethanol Drinking and Reversal Learning Processes in Adolescent Rats: The Impact of Sex and Glycine Transporter Type 1 (GlyT1) Inhibitor
Authors: Filarowska-Jurko Joanna , Komsta Lukasz , Smaga Irena , Surowka Paulina , Marszalek-Grabska Marta , Grochecki Pawel , Nizio Dorota , Filip Malgorzata , Kotlinska Jolanta H.
Published: May 2022

Adverse early life experiences are associated with an enhanced risk for mental and physical health problems, including substance abuse. Despite clinical evidence, the mechanisms underlying these relationships are not fully understood. Maternal separation (MS) is a commonly used animal model of early neglect. The aim of the current study is to determine whether the N-methyl-D-aspartate receptor (NMDAR)/glycine sites are involved in vulnerability to alcohol consumption (two-bottle choice paradigm) and reversal learning deficits (Barnes maze task) in adolescent rats subjected to the MS procedure and whether these effects are sex dependent. By using ELISA, we evaluated MS-induced changes in the NMDAR subunits (GluN1, GluN2A, GluN2B) expression, especially in the glycine-binding subunit, GluN1, in the prefrontal cortex (PFC) and ventral striatum (vSTR) of male/female rats. Next, we investigated whether Org 24598, a glycine transporter 1 (GlyT1) inhibitor, was able to modify ethanol drinking in adolescent and adult male/female rats with prior MS experience and reversal learning in the Barnes maze task. Our findings revealed that adolescent MS female rats consumed more alcohol which may be associated with a substantial increase in GluN1 subunit of NMDAR in the PFC and vSTR. Org 24598 decreased ethanol intake in both sexes with a more pronounced decrease in ethanol consumption in adolescent female rats. Furthermore, MS showed deficits in reversal learning in both sexes. Org 24598 ameliorated reversal learning deficits, and this effect was reversed by the NMDAR/glycine site inhibitor, L-701,324. Collectively, our results suggest that NMDAR/glycine sites might be targeted in the treatment of alcohol abuse in adolescents with early MS, especially females.
Remodeling Osteoarthritic Articular Cartilage under Hypoxic Conditions
Authors: Mohd Yunus Mohd Heikal , Lee Yemin , Nordin Abid , Chua Kien Hui , Bt Hj Idrus Ruszymah
Published: May 2022

Osteoarthritis (OA) is one of the leading joint diseases induced by abnormalities or inflammation in the synovial membrane and articular cartilage, causing severe pain and disability. Along with the cartilage malfunction, imbalanced oxygen uptake occurs, changing chondrocytes into type I collagen- and type X collagen-producing dedifferentiated cells, contributing to OA progression. However, mounting evidence suggests treating OA by inducing a hypoxic environment in the articular cartilage, targeting the inhibition of several OA-related pathways to bring chondrocytes into a normal state. This review discusses the implications of OA-diseased articular cartilage on chondrocyte phenotypes and turnover and debates the hypoxic mechanism of action. Furthermore, this review highlights the new understanding of OA, provided by tissue engineering and a regenerative medicine experimental design, modeling the disease into diverse 2D and 3D structures and investigating hypoxia and hypoxia-inducing biomolecules and potential cell therapies. This review also reports the mechanism of hypoxic regulation and highlights the importance of activating and stabilizing the hypoxia-inducible factor and related molecules to protect chondrocytes from mitochondrial dysfunction and apoptosis occurring under the influence of OA.
Linalool Activates Oxidative and Calcium Burst and CAM3-ACA8 Participates in Calcium Recovery in Arabidopsis Leaves
Authors: Jiao Chunyang , Gong Junqing , Guo Zhujuan , Li Shuwen , Zuo Yixin , Shen Yingbai
Published: May 2022

Plants produce linalool to respond to biotic stress, but the linalool-induced early signal remains unclear. In wild-type Arabidopsis, plant resistance to diamondback moth (Plutella xylostella) increased more strongly in a linalool-treated group than in an untreated control group. H2O2 and Ca2+, two important early signals that participated in biotic stress, burst after being treated with linalool in Arabidopsis mesophyll cells. Linalool treatment increased H2O2 and intracellular calcium concentrations in mesophyll cells, observed using a confocal microscope with laser scanning, and H2O2 signaling functions upstream of Ca2+ signaling by using inhibitors and mutants. Ca2+ efflux was detected using non-invasive micro-test technology (NMT), and Ca2+ efflux was also inhibited by NADPH oxidase inhibitor DPI (diphenyleneiodonium chloride) and in cells of the NADPH oxidase mutant rbohd. To restore intracellular calcium levels, Ca2+-ATPase was activated, and calmodulin 3 (CAM3) participated in Ca2+-ATPase activation. This result is consistent with the interaction between CAM7 and Ca2+-ATPase isoform 8 (ACA8). In addition, a yeast two-hybrid assay, firefly luciferase complementation imaging assay, and an in vitro pulldown assay showed that CAM3 interacts with the N-terminus of ACA8, and qRT-PCR showed that some JA-related genes and defense genes expressions were enhanced when treated with linalool in Arabidopsis leaves. This study reveals that linalool enhances H2O2 and intracellular calcium concentrations in Arabidopsis mesophyll cells; CAM3-ACA8 reduces intracellular calcium concentrations, allowing cells to resume their resting state. Additionally, JA-related genes and defense genes’ expression may enhance plants’ defense when treated with linalool.
Insights into the Mechanism of Human Deiodinase 1
Authors: Rodriguez-Ruiz Alfonso , Braun Doreen , Pflug Simon , Brol Alexander , Sylvester Marc , Steegborn Clemens , Schweizer Ulrich
Published: May 2022

The three isoenzymes of iodothyronine deiodinases (DIO1-3) are membrane-anchored homo-dimeric selenoproteins which share the thioredoxin-fold structure. Several questions regarding their catalytic mechanisms still remain open. Here, we addressed the roles of several cysteines which are conserved among deiodinase isoenzymes and asked whether they may contribute to dimerization and reduction of the oxidized enzyme with physiological reductants. We also asked whether amino acids previously identified in DIO3 play the same role in DIO1. Human DIO1 and 2 were recombinantly expressed in insect cells with selenocysteine replaced with cysteine (DIO1U126C) or in COS7 cells as selenoprotein. Enzyme activities were studied by radioactive deiodination assays with physiological reducing agents and recombinant proteins were characterized by mass spectrometry. Mutation of Cys124 in DIO1 prevented reduction by glutathione, while 20 mM dithiothreitol still regenerated the enzyme. Protein thiol reductants, thioredoxin and glutaredoxin, did not reduce DIO1U126C. Mass spectrometry demonstrated the formation of an intracellular disulfide between the side-chains of Cys124 and Cys(Sec)126. We conclude that the proximal Cys124 forms a selenenyl-sulfide with the catalytic Sec126 during catalysis, which is the substrate of the physiological reductant glutathione. Mutagenesis studies support the idea of a proton-relay pathway from solvent to substrate that is shared between DIO1 and DIO3.
The Distinct Role of the HDL Receptor SR-BI in Cholesterol Homeostasis of Human Placental Arterial and Venous Endothelial Cells
Authors: Strahlhofer-Augsten Manuela , Schliefsteiner Carolin , Cvitic Silvija , George Meekha , Lang-Olip Ingrid , Hirschmugl Birgit , Marsche Gunther , Lang Uwe , Novakovic Boris , Saffery Richard , Desoye Gernot , Wadsack Christian
Published: May 2022

As opposed to adults, high-density lipoprotein (HDL) is the main cholesterol carrying lipoprotein in fetal circulation. The major HDL receptor, scavenger receptor class B type I (SR-BI), contributes to local cholesterol homeostasis. Arterial endothelial cells (ECA) from human placenta are enriched with cholesterol compared to venous endothelial cells (ECV). Moreover, umbilical venous and arterial plasma cholesterol levels differ markedly. We tested the hypothesis that the uptake of HDL-cholesteryl esters differs between ECA and ECV because of the differential expression of SR-BI. We aimed to identify the key regulators underlying these differences and the functional consequences. Immunohistochemistry was used for visualization of SR-BI in situ. ECA and ECV were isolated from the chorionic plate of human placenta and used for RT-qPCR, Western Blot, and HDL uptake assays with 3H- and 125I-labeled HDL. DNA was extracted for the methylation profiling of the SR-BI promoter. SR-BI regulation was studied by exposing ECA and ECV to differential oxygen concentrations or shear stress. Our results show elevated SR-BI expression and protein abundance in ECA compared to ECV in situ and in vitro. Immunohistochemistry demonstrated that SR-BI is mainly expressed on the apical side of placental endothelial cells in situ, allowing interaction with mature HDL circulating in the fetal blood. This was functionally linked to a higher increase of selective cholesterol ester uptake from fetal HDL in ECA than in ECV, and resulted in increased cholesterol availability in ECA. SR-BI expression on ECV tended to decrease with shear stress, which, together with heterogeneous immunostaining, suggests that SR-BI expression is locally regulated in the placental vasculature. In addition, hypomethylation of several CpG sites within the SR-BI promoter region might contribute to differential expression of SR-BI between chorionic arteries and veins. Therefore, SR-BI contributes to a local cholesterol homeostasis in ECA and ECV of the human feto-placental vasculature.
Activation and Function of NLRP3 Inflammasome in Bone and Joint-Related Diseases
Authors: Murakami Tomohiko , Nakaminami Yuri , Takahata Yoshifumi , Hata Kenji , Nishimura Riko
Published: May 2022

Inflammation is a pivotal response to a variety of stimuli, and inflammatory molecules such as cytokines have central roles in the pathogenesis of various diseases, including bone and joint diseases. Proinflammatory cytokines are mainly produced by immune cells and mediate inflammatory and innate immune responses. Additionally, proinflammatory cytokines accelerate bone resorption and cartilage destruction, resulting in the destruction of bone and joint tissues. Thus, proinflammatory cytokines are involved in regulating the pathogenesis of bone and joint diseases. Interleukin (IL)-1 is a representative inflammatory cytokine that strongly promotes bone and cartilage destruction, and elucidating the regulation of IL-1 will advance our understanding of the onset and progression of bone and joint diseases. IL-1 has two isoforms, IL-1α and IL-1β. Both isoforms signal through the same IL-1 receptor type 1, but the activation mechanisms are completely different. In particular, IL-1β is tightly regulated by protein complexes termed inflammasomes. Recent research using innovative technologies has led to a series of discoveries about inflammasomes. This review highlights the current understanding of the activation and function of the NLRP3 (NOD-like receptor family, pyrin domain-containing 3) inflammasome in bone and joint diseases.
Mitochondria-Mediated Cardiovascular Benefits of Sodium-Glucose Co-Transporter 2 Inhibitors
Authors: Dabravolski Siarhei A. , Zhuravlev Alexander D. , Kartuesov Andrey G. , Borisov Evgeny E. , Sukhorukov Vasily N. , Orekhov Alexander N.
Published: May 2022

Several recent cardiovascular trials of SGLT 2 (sodium-glucose cotransporter 2) inhibitors revealed that they could reduce adverse cardiovascular events in patients with T2DM (type 2 diabetes mellitus). However, the exact molecular mechanism underlying the beneficial effects that SGLT2 inhibitors have on the cardiovascular system is still unknown. In this review, we focus on the molecular mechanisms of the mitochondria-mediated beneficial effects of SGLT2 inhibitors on the cardiovascular system. The application of SGLT2 inhibitors ameliorates mitochondrial dysfunction, dynamics, bioenergetics, and ion homeostasis and reduces the production of mitochondrial reactive oxygen species, which results in cardioprotective effects. Herein, we present a comprehensive overview of the impact of SGLT2 inhibitors on mitochondria and highlight the potential application of these medications to treat both T2DM and cardiovascular diseases.
Zebrafish: A New Promise to Study the Impact of Metabolic Disorders on the Brain
Authors: Ghaddar Batoul , Diotel Nicolas
Published: May 2022

Zebrafish has become a popular model to study many physiological and pathophysiological processes in humans. In recent years, it has rapidly emerged in the study of metabolic disorders, namely, obesity and diabetes, as the regulatory mechanisms and metabolic pathways of glucose and lipid homeostasis are highly conserved between fish and mammals. Zebrafish is also widely used in the field of neurosciences to study brain plasticity and regenerative mechanisms due to the high maintenance and activity of neural stem cells during adulthood. Recently, a large body of evidence has established that metabolic disorders can alter brain homeostasis, leading to neuro-inflammation and oxidative stress and causing decreased neurogenesis. To date, these pathological metabolic conditions are also risk factors for the development of cognitive dysfunctions and neurodegenerative diseases. In this review, we first aim to describe the main metabolic models established in zebrafish to demonstrate their similarities with their respective mammalian/human counterparts. Then, in the second part, we report the impact of metabolic disorders (obesity and diabetes) on brain homeostasis with a particular focus on the blood–brain barrier, neuro-inflammation, oxidative stress, cognitive functions and brain plasticity. Finally, we propose interesting signaling pathways and regulatory mechanisms to be explored in order to better understand how metabolic disorders can negatively impact neural stem cell activity.
Optimizing Chain Topology of Bottle Brush Copolymer for Promoting the Disorder-to-Order Transition
Authors: Park Jihoon , Shin Hyun-Woo , Bang Joona , Huh June
Published: May 2022

The order-disorder transitions (ODT) of core-shell bottle brush copolymer and its structural isomers were investigated by dissipative particle dynamics simulations and theoretically by random phase approximation. Introducing a chain topology parameter λ which parametrizes linking points between M diblock chains each with N monomers, the degree of incompatibility at ODT ((χN)ODT; χ being the Flory–Huggins interaction parameter between constituent monomers) was predicted as a function of chain topology parameter (λ) and the number of linked diblock chains per bottle brush copolymer (M). It was found that there exists an optimal chain topology about λ at which (χN)ODT gets a minimum while the domain spacing remains nearly unchanged. The prediction provides a theoretical guideline for designing an optimal copolymer architecture capable of forming sub-10 nm periodic structures even with non-high χ components.
Self-Renewal and Cancers of the Gastric Epithelium: An Update and the Role of the Lectin TFF1 as an Antral Tumor Suppressor
Authors: Hoffmann Werner
Published: May 2022

In 2020, gastric cancer was the fourth leading cause of cancer deaths globally. About 90% of gastric cancers are sporadic and the vast majority are correlated with Helicobacter pylori infection; whereas familial clustering is observed in about 10% of cases. Gastric cancer is now considered to be a disease originating from dysregulated self-renewal of the gastric glands in the setting of an inflammatory environment. The human stomach contains two types of gastric units, which show bi-directional self-renewal from a complex variety of stem cells. This review focuses on recent progress concerning the characterization of the different stem cell populations and the mainly mesenchymal signals triggering their stepwise differentiation as well as the genesis of pre-cancerous lesions and carcinogenesis. Furthermore, a model is presented (Lectin-triggered Receptor Blocking Hypothesis) explaining the role of the lectin TFF1 as an antral tumor suppressor possibly regulating Lgr5+ antral stem cells in a paracrine or maybe autocrine fashion, with neighboring antral gland cells having a role as niche cells.
Histone Modification on Parathyroid Tumors: A Review of Epigenetics
Authors: Conti de Freitas Luiz C. , Castilho Rogerio M. , Squarize Cristiane H.
Published: May 2022

Parathyroid tumors are very prevalent conditions among endocrine tumors, being the second most common behind thyroid tumors. Secondary hyperplasia can occur beyond benign and malignant neoplasia in parathyroid glands. Adenomas are the leading cause of hyperparathyroidism, while carcinomas represent less than 1% of the cases. Tumor suppressor gene mutations such as MEN1 and CDC73 were demonstrated to be involved in tumor development in both familiar and sporadic types; however, the epigenetic features of the parathyroid tumors are still a little-explored subject. We present a review of epigenetic mechanisms related to parathyroid tumors, emphasizing advances in histone modification and its perspective of becoming a promising area in parathyroid tumor research.
DFT Study of Molecular Structure, Electronic and Vibrational Spectra of Tetrapyrazinoporphyrazine, Its Perchlorinated Derivative and Their Al, Ga and In Complexes
Authors: Ryzhov Igor V. , Eroshin Alexey V. , Zhabanov Yuriy A. , Finogenov Daniil N. , Stuzhin Pavel A.
Published: May 2022

Electronic and geometric structures of metal-free, Al, Ga and In complexes with tetrapyrazinoporphyrazine (TPyzPA) and octachlorotetrapyrazinoporphyrazine (TPyzPACl8) were investigated by density functional theory (DFT) calculations and compared in order to study the effect of chlorination on the structure and properties of these macrocycles. The nature of the bonds between metal atoms and nitrogen atoms was described using the NBO-analysis. Simulation and interpretation of electronic spectra were performed with the use of time-dependent density functional theory (TDDFT). A description of calculated IR spectra was carried out based on the analysis of the distribution of the potential energy of normal vibrational coordinates.
Quest for Quality in Translational Stroke Research—A New Dawn for Neuroprotection?
Authors: Haupt Matteo , Gerner Stefan T. , Bähr Mathias , Doeppner Thorsten R.
Published: May 2022

Despite tremendous progress in modern-day stroke therapy, ischemic stroke remains a disease associated with a high socioeconomic burden in industrialized countries. In light of demographic change, these health care costs are expected to increase even further. The current causal therapeutic treatment paradigms focus on successful thrombolysis or thrombectomy, but only a fraction of patients qualify for these recanalization therapies because of therapeutic time window restrictions or contraindications. Hence, adjuvant therapeutic concepts such as neuroprotection are urgently needed. A bench-to-bedside transfer of neuroprotective approaches under stroke conditions, however, has not been established after more than twenty years of research, albeit a great many data have demonstrated several neuroprotective drugs to be effective in preclinical stroke settings. Prominent examples of substances supported by extensive preclinical evidence but which failed clinical trials are tirilazad and disodium 2,4-sulphophenyl-N-tert-butylnitrone (NXY-059). The NXY-059 trial, for instance, was retrospectively shown to have a seriously weak study design, a trial of insufficient quality and a poor statistical analysis, although it initially met the recommendations of the STAIR committee. In light of currently ongoing novel neuroprotective stroke trials, such as ESCAPE-NA, and to avoid the mistakes made in the past, an improvement in study quality in the field of stroke neuroprotection is urgently needed. In the present review, animal models closely reflecting the “typical” stroke patient, occlusion techniques and the appropriate choice of time windows are discussed. In this context, the STAIR recommendations could provide a useful orientation. Taking all of this into account, a new dawn for neuroprotection might be possible.
Fruit Fly Larval Survival in Picked and Unpicked Tomato Fruit of Differing Ripeness and Associated Gene Expression Patterns
Authors: Roohigohar Shirin , Clarke Anthony R. , Strutt Francesca , van der Burg Chloé A. , Prentis Peter J.
Published: May 2022

The larvae of frugivorous tephritid fruit flies feed within fruit and are global pests of horticulture. With the reduced use of pesticides, alternative control methods are needed, of which fruit resistance is one. In the current study, we explicitly tested for phenotypic evidence of induced fruit defences by running concurrent larval survival experiments with fruit on or off the plant, assuming that defence induction would be stopped or reduced by fruit picking. This was accompanied by RT-qPCR analysis of fruit defence and insect detoxification gene expression. Our fruit treatments were picking status (unpicked vs. picked) and ripening stage (colour break vs. fully ripe), our fruit fly was the polyphagous Bactrocera tryoni, and larval survival was assessed through destructive fruit sampling at 48 and 120 h, respectively. The gene expression study targeted larval and fruit tissue samples collected at 48 h and 120 h from picked and unpicked colour-break fruit. At 120 h in colour-break fruit, larval survival was significantly higher in the picked versus unpicked fruit. The gene expression patterns in larval and plant tissue were not affected by picking status, but many putative plant defence and insect detoxification genes were upregulated across the treatments. The larval survival results strongly infer an induced defence mechanism in colour-break tomato fruit that is stronger/faster in unpicked fruits; however, the gene expression patterns failed to provide the same clear-cut treatment effect. The lack of conformity between these results could be related to expression changes in unsampled candidate genes, or due to critical changes in gene expression that occurred during the unsampled periods.
Is MRPI 2.0 More Useful than MRPI and M/P Ratio in Differential Diagnosis of PSP-P with Other Atypical Parkinsonisms?
Authors: Madetko Natalia , Alster Piotr , Kutyłowski Michał , Migda Bartosz , Nieciecki Michał , Koziorowski Dariusz , Królicki Leszek
Published: May 2022

Differential diagnosis of progressive supranuclear palsy remains difficult, especially when it comes to the parkinsonism predominant type (PSP-P), which has a more favorable clinical course. In this entity, especially during the advanced stages, significant clinical overlaps with other tauopathic parkinsonian syndromes and multiple system atrophy (MSA) can be observed. Among the available additional diagnostic methods in every-day use, magnetic resonance imaging (MRI) focused specifically on the evaluation of the mesencephalon seems to be crucial as it is described as a parameter associated with PSP. There is growing interest in relation to more advanced mesencephalic parameters, such as the magnetic resonance parkinsonism index (MRPI) and MRPI 2.0. Based on the evaluation of 74 patients, we demonstrate that only the mesencephalon/pons ratio and MRPI show a significant difference between PSP-P and MSA-parkinsonian type (MSA-P). Interestingly, this differential feature was not maintained by MRPI 2.0. The mesencephalon to pons ratio (M/P), MRPI and MRPI 2.0 were not found to be feasible for the differentiation of PSP-P from other atypical tauopathic syndromes.
Cardiovascular Disease Risk in Rheumatoid Arthritis Anno 2022
Authors: Dijkshoorn Bas , Raadsen Reinder , Nurmohamed Michael T.
Published: May 2022

The risk for developing cardiovascular diseases (CVD) in rheumatoid arthritis (RA) patients is 1.5 times higher compared to the general population. This risk is partly due to the contribution of systemic inflammation in increased atherogenesis, while an increased prevalence of “traditional” cardiovascular risk factors, such as hypertension and dyslipidemia, is also attributed to nearly 50% of the total CVD risk. Most anti-rheumatic medication partly reduces this CVD risk, primarily by reducing inflammation. The increased risk is recognized by most guidelines, which advise consequent screening and multiplying calculated risk scores by 1.5. However, screening in daily clinical practice is poorly done, and RA patients often have undiagnosed and untreated risk factors. In conclusion, even nowadays, RA patients still have an increased risk of developing CVD. Advances in anti-inflammatory treatment partly mitigate this risk, but RA patients need mandatory screening for CV risk factors to turn their CVD risk towards that of the general population.
The Effect of Pre-Emptive Analgesia on the Postoperative Pain in Pediatric Otolaryngology: A Randomized, Controlled Trial
Authors: Zieliński Jakub , Morawska-Kochman Monika , Dudek Krzysztof , Czapla Michał , Zatoński Tomasz
Published: May 2022

The aim of this randomized, controlled trial was to determine whether children undergoing otolaryngological procedures (adenoidectomy, adenotonsillotomy, or tonsillectomy) benefit from pre-emptive analgesia in the postoperative period. Methods: Fifty-five children were assessed for eligibility for the research. Four children refused to participate during the first stage of the study, leaving fifty-one (n = 51) to be randomly assigned either to receive pre-emptive analgesic acetaminophen (15 mg/kg; n = 26) or a placebo (n = 25) in addition to midazolam (0.5 mg/kg) as premedication. All children were anesthetized with sevoflurane, propofol (2–4 mg/kg), and fentanyl (2 mcg/kg). Postoperative pain was assessed using the Visual Analogue Scale (VAS), the Wong–Baker Faces Pain Rating Scale, and the Face, Legs, Activity, Cry, and Consolability (FLACC) scale. The postoperative pain was measured 1, 2, 4, and 6 h after the surgery. Results: The clinical trial reported a statistically significant correlation between administering pre-emptive analgesia (acetaminophen) and reducing pain in children after otolaryngological procedures compared to placebo. The ratio of boys to girls and age were similar among the groups (p > 0.05), so the groups of children were not divided by gender or age. Conclusions: Standard pre-emptive analgesia reduced the severity of pain in the postoperative period after otolaryngological procedures in children. Acetaminophen given before surgery reduces postoperative pain in children undergoing otolaryngological procedures.