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Kupffer cells are a key source of reactive oxygen species (ROS) and are implicated in the development of steatohepatitis and fibrosis in nonalcoholic steatohepatitis (NASH). We recently developed a polythiolated and mannosylated human serum albumin (SH-Man-HSA), a nano-antioxidant that targets Kupffer cells, in which the mannosyl units on albumin allows their specific uptake by Kupffer cells via the mannose receptor C type 1 (MRC1), and in which the polythiolation confers antioxidant activity. The aim of this study was to investigate the therapeutic potential of SH-Man-HSA in NASH model mice. In livers from mice and/or patients with NASH, we observed a reduced blood flow in the liver lobes and the down-regulation in MRC1 expression in Kupffer cells, and SH-Man-HSA alone failed to improve the pathological phenotype in NASH. However, the administration of a nitric oxide (NO) donor restored hepatic blood flow and increased the expression of the mannose receptor C type 2 (MRC2) instead of MRC1. Consequently, treatment with a combination of SH-Man-HSA and an NO donor improved oxidative stress-associated pathology. Finally, we developed a hybrid type of nano-antioxidant (SNO-Man-HSA) via the S-nitrosation of SH-Man-HSA. This nanomedicine efficiently delivered both NO and thiol groups to the liver, with a hepatoprotective effect that was comparable to the combination therapy of SH-Man-HSA and an NO donor. These findings suggest that SNO-Man-HSA has the potential for functioning as a novel nano-therapy for the treatment of NASH.Allergic airway diseases, with incidence augmenting visibly as industrial development and environmental degradation, are characterized by sneezing, itching, wheezing, chest tightness, airway obstruction, and hyperresponsiveness. Current medical modalities attempt to combat these symptoms mostly by small molecule chemotherapeutants, such as corticosteroids, antihistamines, etc., via intranasal approach which is one of the most noninvasive, rapid-absorbed, and patient-friendly routes. Nevertheless, inherent defects for irritation to respiratory mucosa, drug inactivation and degradation, and rapid drug dispersal to off-target sites are inevitable. Lately, intratracheal micro/nano therapeutic systems are emerging as innovative alternatives for airway allergy interventions. This overview introduces several potential application directions of mic/nano-platform in the treatment of airway allergic diseases, including carriers, therapeutic agents, and immunomodulators. The improvement of the existing drug therapy of respiratory allergy management by micro/nano-platform is described in detail. The challenges of the micro/nano-platform nasal approach in the treatment of airway allergy are summarized and the development of micro/nano-platform is also prospected. Although still a burgeoning area, micro/nano therapeutic systems are gradually turning to be realistic orientations as crucial future alternative therapeutic options in allergic airway inflammation interventions.Disulfiram (DSF), a familiar FDA-approved drug used for alcohol withdrawal, has recently been verified with potent antitumor therapeutic effect by generating Cu(DTC)2, which is the complex of its metabolite diethyldithiocarbamate (DTC) and copper. However, its poor tumor selectivity and insufficient endogenous Cu2+ concentration within tumor site largely hinders the application of DSF-based antitumor therapy. Therefore, a GSH-responsive coordination nanoparticles (Cu-IXZ@DSF) was established as a copper carrier to achieve synchronous but separate delivery of Cu2+ and DSF without antitumor ability, further to realize selectively triggered tumor in situ Cu(DTC)2 generation for antitumor therapy. A widely-used proteasome inhibitor ixazomib (IXZ) was chosen as ligands and Cu2+ was used as coordination nodes to form nanosized Cu-IXZ@DSF. The DSF encapsulated in Cu-IXZ@DSF could be reduced to DTC by intracellular GSH, which could contend for Cu2+ and realize in situ high toxic Cu(DTC)2 generation. Meanwhile, the chelation could lead to the disassembly of Cu-IXZ@DSF and release of IXZ to eventually achieve tumor specific "transformation from low toxicity to high toxicity" chemotherapy. The results of in vitro and in vivo experiments demonstrated that the as-prepared nanoplatform Cu-IXZ@DSF showed good biosafety and excellent antitumor effect via endoplasmic reticulum stress (ERS) as well as reactive oxygen species (ROS) generation pathway. Therefore, this nanocarrier provides an inspiring strategy with specific-triggered antitumor Cu(DTC)2 generation for DSF-based chemotherapy with high therapeutic effect and biosafety and showing great potential of treating cancer.Diatoms are currently considered valuable feedstocks for different biotechnological applications. To deepen the knowledge on the production of these microalgae, the diel pattern of batch growth, photosystem II performance, and accumulation of target metabolites of two commercially relevant diatoms, Phaeodactylum tricornutum and Skeletonema costatum, were followed outdoors in 100-L flat panel photobioreactors. S. costatum presented a higher light-to-biomass conversion resulting in higher growth than P. tricornutum. Both fluorescence data and principal component analysis pointed to temperature as a limiting factor for the growth of P. tricornutum. Higher protein and carbohydrate contents were found in P. tricornutum, whereas S. costatum fatty acids were characterized by a higher unsaturation degree. Higher productivities were found at 1 p.m. for protein, lipid, and ash in the case of S. costatum. Overall, S. costatum showed great potential for outdoor cultivation, revealing a broader temperature tolerance and increased biomass productivity than P. tricornutum.Behavioral research supports the efficacy of intervention for reading disability, but the brain mechanisms underlying improvement in reading are not well understood. Here, we review 39 neuroimaging studies of reading intervention to characterize links between reading improvement and changes in the brain. We report evidence of changes in activation, connectivity, and structure within the reading network, and right hemisphere, frontal and sub-cortical regions. Our meta-analysis of changes in brain activation from pre- to post- reading intervention in eight studies did not yield any significant effects. Methodological heterogeneity among studies may contribute to the lack of significant meta-analytic findings. Based on our qualitative synthesis, we propose that brain changes in response to intervention should be considered in terms of interactions among distributed cognitive, linguistic and sensory systems, rather than via a "normalized" vs. "compensatory" dichotomy. Further empirical research is needed to identify effects of moderating factors such as features of intervention programs, neuroimaging tasks, and individual differences among participants.Understanding the pathophysiological mechanism of Parkinson's disease (PD) in the subthalamic nucleus (STN) has become a critical issue since deep brain stimulation (DBS) in this region has been proven as an effective treatment for this disease. The STN possesses a special ability to switch from the spike to the burst firing mode in response to dopamine deficiency in parkinsonism, and this STN burst is considered an electrophysiological signature of the cortico-basal ganglia circuit in the brains of PD patients. This review focuses on the role of STN burst firing in the pathophysiology of PD and during DBS. Here, we review existing literature on how STN bursts originate and the specific factors affecting their formation; how STN burst firing causes motor symptoms in PD and how interventions can rescue these symptoms. Finally, the similarities and differences between the two electrophysiological hallmarks of PD, STN burst firing and beta-oscillation, are discussed. STN burst firing should be considered as a pathophysiological target in PD during treatment with DBS.Uncovering mechanisms that can help explain the experience and impact of anxiety in women is important for improving etiological models and treatments to meet the needs of unique individuals. An enlarged error-related negativity (ERN) - an electrophysiological marker of cognitive control-related error monitoring- represents one indicator of neural processes more strongly related to anxiety in women than men. In this study, we further examined this association in women by testing the moderating effect of hormonal contraceptive (HC) use on the relationship between worry - i.e., a transdiagnostic cognitive dimension of anxiety - and the ERN. Results revealed that HCs moderated the worry-ERN association. Specifically, we found a significant and large relationship between worry and enlarged ERN in women using HCs, which was smaller and nonsignificant in naturally cycling women (i.e., those not using HCs). These findings suggest that the interplay among HC use, error-related cognitive control, and worry represents a novel mechanism for better characterizing the expression and impact of worry in women.Visual recognition occurs rapidly at multiple categorization levels, including the superordinate level (e.g., animal), basic level (e.g., cat), or exemplar level (e.g., my cat). Visual search for animals is faster than for man-made objects, even when the images from those categories have comparable gist statistics (i.e., low- or mid-level visual information), which suggests that higher-level, conceptual influences may support this search advantage for animals. However, it remains unclear whether the search advantage can be explained in part by early visual search processes via the N2pc ERP component, which emerges earlier than behavioral responses, across different categorization levels. Participants searched for 1) an exact image (e.g., a specific squirrel image, Exemplar-level Search), 2) any images of an item (e.g., any squirrels, Basic-level Search), or 3) any items in a category (e.g., any animals, Superordinate-level Search). In addition to Target Present trials, Foil trials measured involuntary attentional selection of task-irrelevant images related to the targets (e.g., other squirrel images when searching for a specific squirrel image, or other animals when searching for squirrels). ERP results revealed 1) a larger N2pc amplitude during Foil trials in Exemplar-level Search for animals than man-made objects, and 2) faster onset latencies for animal search than man-made object search across all categorization levels. These results suggest that the search advantage for animals over man-made objects emerges early, and that attentional selection is more biased toward the basic-level (e.g., squirrel) for animals than for man-made objects during visual search.The evaluation of nano-priming effect with galactomannan stabilized Phyto-complexed calcium hydroxide (Ca(OH)2), selenium oxyanion‑calcium hydroxide SeO-(Ca(OH)2), and selenium‑calcium hydroxide Se-(Ca(OH)2) nanocomposites was carried out in Vigna radiata (Green gram) seeds. The green source Cassia angustifolia seed rich in galactomannan and other phytoconstituents was detected experimentally and characterized with GC-MS, UV, FT-IR, NMR, XRD, and SEM studies. The highly active galactomannan and other biomolecules, enable their terminal oxygen and hydroxide groups to bind with calcium and selenium ions through bidentate and monodentate chelation, followed by bio-reduction. click here On the mild-thermal agitation, bio-stabilized (Ca(OH)2), SeO-(Ca(OH)2), and Se-(Ca(OH)2) nanocomposite coated with seed-derived biomolecules were precipitated under an alkaline condition. The size and morphological parameters of bio-fabricated nanocomposites were characterized to exhibit the spherical and hexagonal shape in nanoscale images of size 17.
Homepage: https://www.selleckchem.com/GSK-3.html
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