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  • Article
    Roy R, Soldin SJ, Stolze B, Barbieri M, Tawalbeh SM, Rouhana N, Fronczek AE, Nagaraju K, van den Anker J, Dang UJ, Hoffman EP.
    Steroids. 2022 02;178:108953.
    Pharmacological glucocorticoids are the most prescribed anti-inflammatory medications, and are chemical variants of cortisol, the circadian and stress hormone. Both endogenous and pharmacological glucocorticoids bind the glucocorticoid receptor (NR3C1) with high affinity, and both then bind downstream gene promoter elements (GRE) to drive positive gene transcription of many proteins. Glucocorticoid/GR complexes also bind distinct negative gene promoter elements (nGRE) to inhibit expression of genes involved in NF-κB innate immunity signaling. We sought to define the acute response of a single dose of prednisone (0.2 mg/kg) in young adult volunteers, with blood samples taken at baseline, 2, 3, 4 and 6 h post-oral dose. To control for circadian morning cortisol hitting the same molecular pathways, a day of blood draws was done without oral prednisone (same time of day), one day prior to drug day. Serum samples were processed for steroid hormone profiles (mass spectrometry; 9 steroidal hormones), proteomics (SOMAscan aptamer panels, 1,305 proteins), and inflammatory markers (Meso Scale Discovery; 10 pro-inflammatory cytokines). The pharmacological effect of the prednisone dose was shown by significant declines of adrenal steroids by 3 h after dosing. IL-10 showed drug-related increase to 4 hrs, then decrease to 6 hrs. IL-8 showed drug-related decrease in serum by 4 h, consistent with direct negative action of GR/ligand on IL-8 gene promoter. Proteomics data showed beta-2 microglobulin, TNFSF15, TSH, CST3, NBL1 to show time-related decreases with prednisone, while CXCL13 showed increases, although these require validation. In summary, a single low dose of prednisone leads to broad suppression of the adrenal axis within 3 h, and down-regulation of inflammatory serum proteins by 6 h.
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  • Article
    Phillips T, Gaoue OG, Lenhart S, Strickland WC.
    Math Biosci. 2023 01;355:108953.
    Several forest plant species are harvested both lethally for their timber and non-lethally for their non-timber forest products by the local people for cultural and economic reasons. To maximize yield, harvesters target various life stages of these species including both adults and juveniles particularly when the number of harvestable adults decline. The demographic consequences of harvesting various plant sizes differ based on what life stage is targeted. In this paper, we develop a size-structured, seasonal system of difference equations and corresponding matrix model with time-varying harvest to model the effects of size-dependent harvesting strategies on the population dynamics of tropical trees. We illustrate numerically our work specifically on African mahogany, Khaya senegalensis, a tropical tree in Benin. Novel applications and combinations of previously established matrix compression algorithms are presented to determine certain rates in our model, with other rates coming from the use of generalized linear modeling and ordinary least squares estimation incorporating observed population data. Harvesting rates for two types of populations are estimated, one with simulated harvest and the other experiencing natural harvest. Eigenvalue analysis suggests that for the populations in our study, harvesting may not have a drastic effect on the long-term persistence of the population. However, this should be taken with caution given that our model does not account for stochastic environmental variations that can interactively reduce population growth rates.
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  • Article
    Shen J, Yu D, Liu Z, Di H, He JZ.
    Environ Int. 2024 Sep;191:108953.
    Land use conversion in estuary wetlands may affect the transmission of antibiotic resistance genes (ARGs), while the risk rank of the ARGs and the change of clinically relevant ARGs under various land-use types are not well understood. This study used metagenomics to reveal the diversity and abundance of ARGs across five distinct land uses: reed wetland, tidal flat, grassland, agricultural land and fallow land, as well as their distribution and potential health risks. Results showed that high numbers of ARG subtypes and classes were detected irrespective of land-use types, notably higher in agricultural land (144 ARG subtypes). The most shared ARG subtypes were multidrug resistance genes across all the land uses (29 subtypes, 4.7 × 10-2-1.5 × 10-1 copies per 16S rRNA gene copy). Proteobacteria and Actinobacteria were primary ARG hosts, with 18 and 15 ARGs were found in both of them, respectively. The ARG subtype mdtB was the most dominant clinical ARG detected with 90 % amino acid identity. The change of ARGs exhibited a consistent trend across land uses in terms of health risk ranks, with the highest observed in fallow land and the lowest in reed wetland. This study reveals the distribution pattern of ARGs across various land-use types, and enhances our understanding of the potential health risks associated with ARGs in the context of coastal wetland conversion in estuary areas.
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  • Article
    Quass GL, Kral A.
    Hear Res. 2024 03 01;443:108953.
    The present study investigates effects of current focusing and pulse shape on threshold, dynamic range, spread of excitation and channel interaction in the time domain using cochlear implant stimulation. The study was performed on 20 adult guinea pigs using a 6-channel animal cochlear implant, recording was performed in the auditory midbrain using a multielectrode array. After determining the best frequencies for individual recording contacts with acoustic stimulation, the ear was deafened and a cochlear implant was inserted into the cochlea. The position of the implant was controlled by x-ray. Stimulation with biphasic, pseudomonophasic and monophasic stimuli was performed with monopolar, monopolar with common ground, bipolar and tripolar configuration in two sets of experiments, allowing comparison of the effects of the different stimulation strategies on threshold, dynamic range, spread of excitation and channel interaction. Channel interaction was studied in the temporal domain, where two electrodes were activated with pulse trains and phase locking to these pulse trains in the midbrain was quantified. The results documented multifactorial influences on the response properties, with significant interaction between factors. Thresholds increased with increasing current focusing, but decreased with pseudomonophasic and monophasic pulse shapes. The results documented that current focusing, particularly tripolar configuration, effectively reduces channel interaction, but that also pseudomonophasic and monophasic stimulation and phase duration intensity coding reduce channel interactions.
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  • Article
    Tatum J, Punia A, Kostiuk L, Secanell M, Olfert J.
    Data Brief. 2023 Apr;47:108953.
    Methane pyrolysis is a process used to generate hydrogen gas and carbon black without the creation of carbon dioxide. Methane pyrolysis in a constant volume batch reactor was investigated at temperatures of 892, 1093, and 1292 K with reaction times of 15, 30, 60, 180, and 300 s at an initial pressure of 399 kPa. A quartz vessel (32 mL) was placed inside an oven where it was heated to high temperatures. At the beginning of the process, the quartz vessel was vacuumed, then flushed with nitrogen before being vacuumed again prior to every experiment. Pressurized methane was then injected into the vessel for an allocated reaction time and collected in a sample bag post reaction for analysis. The molar concentration of the product gas was analyzed using gas chromatography. Hydrogen molar concentration increased as temperature and reaction time increased. For experiments completed at 892 K the hydrogen molar concentration varied from 10.0 ± 5.9% with a 15 s reaction time to 26.5 ± 0.8% for a 300 s reaction time. For experiments completed at 1093 K the hydrogen molar concentration varied from 21.8 ± 3.7% for a 15 s reaction time to 53.0 ± 2.9% for a 300 s reaction time. For experiments completed at 1292 K the hydrogen molar concentration varied from 31.5 ± 1.7% for a 15 s reaction time to 53.0 ± 2.4% for a 300 s reaction time.
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  • Article
    Liang R, Yuan Y, Bai Y, Liu X, Chen J, Jiang D, Meng D, Chen G, Li B, Zhou L, Guo W.
    Int Immunopharmacol. 2022 Sep;110:108953.
    Neobavaisoflavone (NBIF), a monomolecular compound extracted from Psoralea corylifolia (Leguminosae), is commonly used in traditional Chinese medicine for multiple purposes. NBIF is known to exert anti-fungal and anti-tumor effects, and promote bone formation. Whether NBIF exhibits anti-allergic effects by regulating mast cell activation remains unclear. Therefore, we designed this study to investigate the anti-allergic effects of NBIF on IgE/Ag-induced mouse bone marrow-derived mast cells and ovalbumin-induced asthma, and the passive systemic anaphylaxis (PSA) reaction in mice. Our results showed that NBIF suppresses the production of leukotriene C4, prostaglandin D2 and inflammatory cytokines, and decreases the degranulation of BMMCs stimulated by IgE/Ag. A thorough investigation ascertained that NBIF suppresses the phosphorylation of mitogen-activated protein kinases, and represses the nuclear factor-κB-related signaling pathway. In addition, the oral administration of NBIF in mice inhibited the IgE-induced PSA reaction in a dose-dependent manner. Overall, we provide new insights into how NBIF regulates the IgE/Ag-mediated signaling pathways. Moreover, our investigation promotes the potential use of NBIF in treating allergy and asthma.
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  • Article
    Ikeno Y, Inomata M, Tsukimura Y, Suzuki Y, Takeuchi H, Harada Y, Kon R, Ikarashi N, Chiba Y, Yamada T, Kamei J, Sakai H.
    J Nutr Biochem. 2022 05;103:108953.
    Previously it was shown that cisplatin causes muscle atrophy. Under this condition, cisplatin increased the expression of atorogenes, such as muscle ring finger 1 and atrogin-1 (also known as muscle atrophy F-box protein), in mouse skeletal muscle. It was reported recently that ubiquitin (Ub) and ubiquitinated protein levels in skeletal muscle were also up-regulated in cisplatin-induced muscle atrophy, and cisplatin-induced ubiquitinated proteins were degraded by the 26S proteasome pathway. Eicosapentaenoic acid (EPA) is effective against skeletal muscle atrophy in mice. However, it is unclear how EPA suppresses the Ub-proteasome pathway. In this study, the effect of EPA on cisplatin-induced muscle atrophy in mice was examined. Mice were intraperitoneally injected with cisplatin or vehicle control once daily for 4 d. EPA or its vehicle was orally administered 30 min before cisplatin administration. Cisplatin systemic administration induced decrease in muscle mass, myofiber diameter, and increase in Ub genes and ubiquitinated proteins in mouse skeletal muscle were recovered by co-treatment with EPA. However, weight loss and up-regulated atrogenes induced by cisplatin were not changed by co-treatment with EPA in skeletal muscle. In this study, EPA attenuated cisplatin-induced muscle atrophy via down-regulation of up-regulated Ub gene expression. Although further clinical studies are needed, EPA administration can be effective in the development of muscle atrophy in cisplatin-treated patients.
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  • Article
    Zhu Y, Uytiepo M, Bushong E, Haberl M, Beutter E, Scheiwe F, Zhang W, Chang L, Luu D, Chui B, Ellisman M, Maximov A.
    Cell Rep. 2021 04 06;35(1):108953.
    Chemical synapses of shared cellular origins have remarkably heterogeneous structures, but how this diversity is generated is unclear. Here, we use three-dimensional (3D) electron microscopy and artificial intelligence algorithms for image processing to reconstruct functional excitatory microcircuits in the mouse hippocampus and microcircuits in which neurotransmitter signaling is permanently suppressed with genetic tools throughout the lifespan. These nanoscale analyses reveal that experience is dispensable for morphogenesis of synapses with different geometric shapes and contents of membrane organelles and that arrangement of morphologically distinct connections in local networks is stochastic. Moreover, loss of activity increases the variability in sizes of opposed pre- and postsynaptic structures without disrupting their alignments, suggesting that inherently variable weights of naive connections become progressively matched with repetitive use. These results demonstrate that mechanisms for the structural diversity of neuronal synapses are intrinsic and provide insights into how circuits essential for memory storage assemble and integrate information.
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  • Article
    Vardi R, Berger-Tal O, Roll U.
    Biol Conserv. 2021 Feb;254:108953.
    Restricted human activity during the COVID-19 pandemic raised global attention to the presence of wildlife in cities. Here, we analyzed iNaturalist observations of prominent wildlife species around North-American urban centers, before and during the COVID-19 pandemic outbreak. We suggest that the popular notion of 'wildlife reclaiming cities' may have been exaggerated. We found that while pumas ventured deeper into urban habitats during the COVID-19 pandemic, bears, bobcats, coyotes, and moose did not. Species differential behavioral responses may highlight their evolutionary history cohabiting human habitats. Nevertheless, our results highlight the importance of urban nature for people during the pandemic. Our insights could help manage urban wildlife, better plan greenspaces, and promote positive nature engagements.
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  • Article
    Krunt O, Zita L, Kraus A, Bureš D, Needham T, Volek Z.
    Meat Sci. 2022 Nov;193:108953.
    The present study analysed the effect of housing system (caged versus penned) on the growth performance, carcass traits, and meat quality of rabbits. The physiochemical quality of five muscles was evaluated, together with the chemical composition and fatty acid profile of the meat from the hind leg. Sensory properties of the longissimus lumborum (LL) was also assessed. The LL yields were higher in caged rabbits. According to the results, meat from rabbits raised in cages had higher b* values for the LL (i.e., meat was yellower) than rabbits raised in pens. In addition, the quadriceps femoris from penned rabbits had higher a* and b* values (i.e., were redder and yellower) than caged rabbits. The MUFAs (18:1 n-9 and 20:1 n-9) and ash contents of the hind leg meat were higher in caged rabbits. In conclusion, while housing system influenced the physiochemical traits of rabbit meat, the sensory properties were not influenced.
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  • Article
    Li X, Chen X, Hu S, Xu J, Liu Z.
    iScience. 2024 Feb 16;27(2):108953.
    The maximum clique (MC) problem holds significance in network analysis. Quantum-based algorithms have recently emerged as promising approaches for this problem. However, these algorithms heavily depend on parameters of quantum system and vary significantly for different graphs. In order to tackle this issue, we initially demonstrate that continuous-time quantum walks (CTQW) driven by the Seidel matrix offer valuable insights into the clique structure of graphs, outperforming the CTQW driven by adjacency matrix. Specifically, we conduct an in-depth analysis for CTQW of 4 types of graphs, meticulously calculating the amplitudes associated with different vertices. Our findings consistently reveal that vertices belonging to MC exhibit the highest intensity at the largest frequency component of the probability amplitude for these types of graphs. Considering the varying intensities, we propose a parameter-independent algorithm for determining the MC. We compare our algorithm with a typical quantum-based algorithm, the results indicate that our algorithm exhibits greater stability.
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  • Article
    Parmes E, Pesce G, Sabel CE, Baldacci S, Bono R, Brescianini S, D'Ippolito C, Hanke W, Horvat M, ... Show More Liedes H, Maio S, Marchetti P, Marcon A, Medda E, Molinier M, Panunzi S, Pärkkä J, Polańska K, Prud'homme J, Ricci P, Snoj Tratnik J, Squillacioti G, Stazi MA, Maesano CN, Annesi-Maesano I.
    Environ Res. 2020 04;183:108953.
    INTRODUCTION: Recent research focused on the interaction between land cover and the development of allergic and respiratory disease has provided conflicting results and the underlying mechanisms are not fully understood. In particular, green space, which confers an overall positive impact on general health, may be significantly contributing to adverse respiratory health outcomes. This study evaluates associations between surrounding residential land cover (green, grey, agricultural and blue space), including type of forest cover (deciduous, coniferous and mixed), and childhood allergic and respiratory diseases.
    METHODS: Data from 8063 children, aged 3-14 years, were obtained from nine European population-based studies participating in the HEALS project. Land-cover exposures within a 500 m buffer centred on each child's residential address were computed using data from the Coordination of Information on the Environment (CORINE) program. The associations of allergic and respiratory symptoms (wheeze, asthma, allergic rhinitis and eczema) with land coverage were estimated for each study using logistic regression models, adjusted for sex, age, body mass index, maternal education, parental smoking, and parental history of allergy. Finally, the pooled effects across studies were estimated using meta-analyses.
    RESULTS: In the pooled analyses, a 10% increase in green space coverage was significantly associated with a 5.9%-13.0% increase in the odds of wheezing, asthma, and allergic rhinitis, but not eczema. A trend of an inverse relationship between agricultural space and respiratory symptoms was observed, but did not reach statistical significance. In secondary analyses, children living in areas with surrounding coniferous forests had significantly greater odds of reporting wheezing, asthma and allergic rhinitis.
    CONCLUSION: Our results provide further evidence that exposure to green space is associated with increased respiratory disease in children. Additionally, our findings suggest that coniferous forests might be associated with wheezing, asthma and allergic rhinitis. Additional studies evaluating both the type of green space and its use in relation to respiratory conditions should be conducted in order to clarify the underlying mechanisms behind associated adverse impacts.
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  • Article
    Berg AT, Kaat AJ, Gaebler-Spira D.
    Epilepsy Behav. 2022 12;137(Pt A):108953.
    OBJECTIVE: Developmental and epileptic encephalopathies (DEE) entail moderate to profound impairments in gross motor skills and mobility, which are poorly quantified with clinical outcomes assessments (COA) used in neuro-typical populations. We studied the motor domain of the Adaptive Behavior Assessment System-3 for ages 0-5 years (ABAS) used outside of its intended age range with a focus on raw scores.
    METHODS: In a cross-sectional survey, 117 parents of children with a variety of DEEs (ages 1-35 years, median = 9) completed the motor domain section of the ABAS. Floor and ceiling effects and associations with epilepsy-related factors were assessed with appropriate parametric and nonparametric statistical techniques. The sensitivity of the ABAS and additional measures of mobility borrowed from the cerebral palsy literature (Functional Activities Questionnaire (FAQ-22) walking level (FAQ-WL)) to different levels of the Functional Mobility Scale was determined.
    RESULTS: ABAS motor scores corresponded to a median age equivalent of 20.5 months (Inter-Quartile Range (IQR) 8-34). Most raw scores corresponded to standardized scores > 2 standard deviations below the ABAS standardization sample mean. ABAS raw scores demonstrated minimal floor and ceiling effects (<5%). In linear regression models, scores increased with age under 6 years (p < 0.0001) but flattened out thereafter. Scores varied substantially by DEE group (p < 0.001) and decreased with higher convulsive seizure frequency (<0.0001) and number of seizure medications (p < 0.001). ABAS and other motor scores were sensitive to important differences in mobility as represented by the FMS at 5 yards. Further, they correlated with declines in mobility function from 5 to 500 yards.
    SIGNIFICANCE: An out-of-range COA with raw scores may provide a measure of motor ability and mobility sensitive within the range of moderate to profound impairment seen in patients with DEE. This approach could shorten the time to appropriate COA development and ensure timely clinical trial readiness for novel therapies for rare DEEs.
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  • Article
    Ozaki E, Delaney C, Campbell M, Doyle SL.
    Exp Eye Res. 2022 04;217:108953.
    As the resident immune cells in the retina, microglia play important homeostatic roles in retinal immune regulation and neuroprotection. However, chronic microglia activation is a common hallmark of many degenerative retinal diseases. The semi-synthetic tetracycline antibiotic, minocycline, appears to inhibit pro-inflammatory microglia which coincides with protection against photoreceptor cell degeneration. A sub-type of microglia termed disease associated microglia (DAM) have recently been associated with a wide range of central nervous system (CNS) diseases. In this study we examine the kinetics of microglia infiltration towards the outer retina of rhodopsin knockout mice (Rho-/-) by immunofluorescence, and undertake transcriptional and spatial localization analysis of markers for evidence of both homeostatic function and appearance of DAM. We demonstrate in the Rho-/- mice, IBA1+ and P2RY12+ microglia take on an activated morphology early in disease, prior to notable photoreceptor loss and are capable of infiltrating the subretinal space. Expression of lipid processing enzyme and DAM-marker lipoprotein lipase (LPL) is primarily observed only after microglia have traversed the ONL. Administration of minocycline to Rho-/- mice induced loss of phagocytic/DAM microglia in the outer retina in vivo coinciding with photoreceptor survival and amelioration of retinal degeneration. Overall, we show that minocycline suppresses many DAM markers, in particular those associated with lipid metabolism indicating that suppression of this process is one mechanism by which minocycline protects against inflammation induced photoreceptor cell death.
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  • Article
    Zhao YN, Wang H, Su LL, Wang HQ, Zhang BJ, Su Y.
    Vet Microbiol. 2021 Mar;254:108953.
    Strangles is an acute and frequently diagnosed infectious disease caused by Streptococcus equi subsp. equi. Infection with this pathogen can cause grave losses to the equine industry. The present work investigates glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an important surface-localized virulence factor of S. equi, to determine whether it could be developed into an efficacious and suitable subunit vaccine against strangles. Two different recombinant fragments of S. equi GAPDH, namely, GAPDH-L and GAPDH-S, were constructed and expressed. Further, the antigenicity and immunogenicity of these two recombinant proteins were compared and evaluated in a mouse model. Our results revealed that immune responses were efficiently induced by the proteins in immunized mice. Remarkably, higher survival rates and significantly lower bacterial loads in the lung, liver, kidney, and spleen were observed in the GAPDH-S group compared with the GAPDH-L group after challenge with S. equi. High levels of specific antibodies, elevated antibody titers, and increased proportions of CD8 + T cells further indicated that GAPDH-S elicited better humoral and cellular immune responses than GAPDH-L. Furthermore, the induction of TCR, TLR-2, TLR-3, and TLR-4 significantly increased in the GAPDH-S group compared with those in the GAPDH-L and negative control groups. In summary, our results indicate that the optimized recombinant protein GAPDH-S is a promising candidate construct that may be further developed into a multivalent subunit vaccine for strangles.
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  • Article
    Zeng M, Zhang X, Zhao C, Lu X, Meng Q.
    J Neurosci Methods. 2021 01 01;347:108953.
    BACKGROUND: The classification of epileptiform electroencephalogram (EEG) signals has been treated as an important but challenging issue for realizing epileptic seizure detection. In this work, combing gray recurrence plot (GRP) and densely connected convolutional network (DenseNet), we developed a novel classification system named GRP-DNet to identify seizures and epilepsy from single-channel, long-term EEG signals.
    NEW METHODS: The proposed GRP-DNet classification system includes three main modules: 1) input module takes an input long-term EEG signal and divides it into multiple short segments using a fixed-size non-overlapping sliding window (FNSW); 2) conversion module transforms short segments into GRPs and passes them to the DenseNet; 3) fusion and decision, the predicted label of each GRP is fused using a majority voting strategy to make the final decision.
    RESULTS: Six different classification experiments were designed based on a publicly available benchmark database to evaluate the effectiveness of our system. Experimental results showed that the proposed GRP-DNet achieved an excellent classification accuracy of 100 % in each classification experiment, Furthermore, GRP-DNet gave excellent computational efficiency, which indicates its tremendous potential for developing an EEG-based online epilepsy diagnosis system.
    COMPARISON WITH EXISTING METHODS: Our GRP-DNet system was superior to the existing competitive classification systems using the same database.
    CONCLUSIONS: The GRP-DNet is a potentially powerful system for identifying and classifying EEG signals recorded from different brain states.
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  • Article
    Ren F, Nian Y, Perussello CA.
    Food Res Int. 2020 06;132:108953.
    Onions play an important part in the daily diet for most populations around the world owing to their nutritional composition and their unique capacity to naturally flavor dishes. Onions contain quercetin and its derivatives - the predominant flavonoid in onions that exert a great contribution to the effective bioactive properties of onion, including its derived products. The present paper comprehensively reviewed flavonoids (with a specific focus on quercetin in onions): their chemical composition, distribution, bioactivities in onion, and impacting factors with a focus on how they can be affected by various post-harvest conditions (storage and food processing). In addition, research on the extraction of flavonoid compounds from onions using a number of novel technologies was also reviewed.
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  • Article
    Harley ITW, Sawalha AH.
    Clin Immunol. 2022 03;236:108953.
    Systemic lupus erythematosus is the prototypical systemic autoimmune disease, as it is characterized both by protean multi-organ system manifestations and by the uniform presence of pathogenic autoantibodies directed against components of the nucleus. Prior to the modern genetic era, the diverse clinical manifestations of SLE suggested to many that SLE patients were unlikely to share a common genetic risk basis. However, modern genetic studies have revealed that SLE usually arises when an environmental exposure occurs in an individual with a collection of genetic risk variants passing a liability threshold. Here, we summarize the current state of the field aimed at: (1) understanding the genetic architecture of this complex disease, (2) synthesizing how this genetic risk architecture impacts cellular and molecular disease pathophysiology, (3) providing illustrative examples that highlight the rich complexity of the pathobiology of this prototypical autoimmune disease and (4) communicating this complex etiopathogenesis to patients.
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  • Article
    Ciardullo G, Orlando C, Russo N, Marchese E, Galano A, Marino T, Prejanò M.
    Comput Biol Med. 2024 Sep;180:108953.
    Natural antioxidants have become the subject of many investigations due to the role that they play in the reduction of oxidative stress. Their main scavenging mechanisms concern the direct inactivation of free radicals and the coordination of metal ions involved in Fenton-like reactions. Recently, increasing attention has been paid to non-covalent inhibition of enzymes involved in different diseases by the antioxidants. Here, a computational investigation on the primary antioxidant power of (+)-catechin against the •OOH radical has been performed in both lipid-like and aqueous environments, taking into account the relevant species present in the simulated acid-base equilibria at the physiological pH. Hydrogen Atom Transfer (HAT), Single Electron Transfer (SET), and Radical Adduct Formation (RAF) mechanisms were studied, and relative rate constants were estimated. The potential inhibitory activity of the (+)-catechin towards the most important proteases from SARS-CoV-2, 3C-like (Mpro) and papain-like (PLpro) proteases was also investigated by MD simulations to provide deeper atomistic insights on the binding sites. Based on the antioxidant and antiviral properties also unravelled by comparison with other molecules having similar chemical scaffold, our results propose that (+)-CTc satisfies can explicate a dual action as antioxidant and antiviral in particular versus Mpro from SARS-CoV-2.
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  • Article
    Zhu K, Jiang B, Hu R, Yang Y, Miao M, Li Y, Liu Z.
    PLoS One. 2014;9(9):e108953.
    BACKGROUND: CXCL12 is a small chemotactic cytokine belonging to the CXC chemokine family expressed in various organs. It contributes to the migration, invasion and angiogenesis of cancer cells. Recently, the CXCL12 G801A polymorphism was shown to be associated with an increased risk of various kinds of cancers, but the results were too inconsistent to be conclusive.
    METHODS: To solve the problem of inadequate statistical power and conflicting results, a meta-analysis of published case-control studies was performed, including 4,435 cancer cases and 6,898 controls. Odds ratios (ORs) and their 95% confidence intervals (CIs) were used to determine the strength of association between CXCL12 G801A polymorphism and cancer risk.
    RESULTS: A significant association between CXCL12 G801A polymorphism and cancer risk was found under all genetic models. Further, subgroup analysis stratified by ethnicity suggested a significant association between CXCL12 G801A polymorphism and cancer risk in the Asian subgroup under all genetic models. However, in the Caucasian subgroup, a significant association was only found under an additive genetic model and a dominant genetic model. The analysis stratified by cancer type found that CXCL12 G801A polymorphism may increase the risk of breast cancer, lung cancer, and "other" cancers. Based on subgroup stratified by source of controls, a significant association was observed in hospital-based studies under all genetic models.
    CONCLUSIONS: The CXCL12 G801A polymorphism is associated with an increased risk of cancer based on current published data. In the future, large-scale well-designed studies with more information are needed to better estimate possible gene-gene or gene-environment interactions.
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