Saturated fatty acids can activate Toll-like receptor 2 (TLR2) and TLR4 but polyunsaturated fatty acids, particularly docosahexaenoic acid (DHA) inhibit the activation. Lipopolysaccharides (LPS) and ...lipopetides, ligands for TLR4 and TLR2, respectively, are acylated by saturated fatty acids. Removal of these fatty acids results in loss of their ligand activity suggesting that the saturated fatty acyl moieties are required for the receptor activation. X-ray crystallographic studies revealed that these saturated fatty acyl groups of the ligands directly occupy hydrophobic lipid binding domains of the receptors (or co-receptor) and induce the dimerization which is prerequisite for the receptor activation. Saturated fatty acids also induce the dimerization and translocation of TLR4 and TLR2 into lipid rafts in plasma membrane and this process is inhibited by DHA. Whether saturated fatty acids induce the dimerization of the receptors by interacting with these lipid binding domains is not known. Many experimental results suggest that saturated fatty acids promote the formation of lipid rafts and recruitment of TLRs into lipid rafts leading to ligand independent dimerization of the receptors. Such a mode of ligand independent receptor activation defies the conventional concept of ligand induced receptor activation; however, this may enable diverse non-microbial molecules with endogenous and dietary origins to modulate TLR-mediated immune responses. Emerging experimental evidence reveals that TLRs play a key role in bridging diet-induced endocrine and metabolic changes to immune responses.
Regenerative medicine involves interdisciplinary biomimetic approaches for cell therapy and tissue regeneration, employing the triad of cells, signals, and/or scaffolds. Remarkably, the field of ...therapeutic cells has evolved from the use of embryonic and adult stem cells to the use of induced pluripotent stem cells. For application of these cells in regenerative medicine, cell fate needs to be carefully controlled via external signals, such as the physical properties of an artificial extracellular matrix (ECM) and biologically active molecules in the form of small molecules, peptides, and proteins. It is therefore crucial to develop biomimetic scaffolds, reflecting the nanoenvironment of three-dimensional (3D) ECM in the body. Here, we describe in situ-forming injectable hydrogel systems, prepared using a variety of chemical crosslinkers and/or physical interactions, for application in regenerative medicine. Selective and fast chemical reactions under physiological conditions are prerequisites for in situ formation of injectable hydrogels. These hydrogels are attractive for regenerative medicine because of their ease of administration, facile encapsulation of cells and biomolecules without severe toxic effects, minimally invasive treatment, and possibly enhanced patient compliance. Recently, the Michael addition reaction between thiol and vinyl groups, the click reaction between bis(yne) molecules and multiarm azides, and the Schiff base reaction have been investigated for generation of injectable hydrogels, due to the high selectivity and biocompatibility of these reactions. Noncovalent physical interactions have also been proposed as crosslinking mechanisms for in situ forming injectable hydrogels. Hydrophobic interactions, ionic interactions, stereocomplex formation, complementary pair formation, and host–guest interactions drive the formation of 3D polymeric networks. In particular, supramolecular hydrogels have been developed using the host–guest chemistry of cyclodextrin (CD) and cucurbituril (CB), which allows highly selective, simple, and biocompatible crosslinking. Molecular recognition and complex formation of supramolecules, without the need for additional additives, have been successfully applied to the 3D network formation of polymer chains. Finally, we review the current state of the art of injectable hydrogel systems for application in regenerative medicine, including cell therapy and tissue regeneration.
Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary complication in patients with hematologic malignancies or systemic autoimmune disorders. Pathologic findings show pulmonary ...capillaritis, bland hemorrhage, diffuse alveolar damage, and hemosiderin-laden macrophages, but in the majority of cases, pathogenesis remains unclear. Despite the severity and high mortality, the current treatment options for DAH remain empirical. Systemic treatment to control inflammatory activity including high-dose corticosteroids, cyclophosphamide, and rituximab and supportive care have been applied, but largely unsuccessful in critical cases. Activated recombinant factor VII (FVIIa) can achieve rapid local hemostasis and has been administered either systemically or intrapulmonary for the treatment of DAH. However, there is no randomized controlled study to evaluate the efficacy and safety, and the use of FVIIa for DAH remains open to debate. This review discusses the pathogenesis, diverse etiologies causing DAH, diagnosis, and treatments focusing on hemostasis using FVIIa. In addition, the risks and benefits of the off-label use of FVIIa in pediatric patients will be discussed in detail.
Recently, organic thermally activated delayed fluorescence (TADF) emitters have attracted a great deal of attention because they can theoretically realize 100% internal quantum efficiency. Many TADF ...emitters have been developed since the first demonstration of close to 20% external quantum efficiency in the devices. Recently developed TADF emitters demonstrated close to 37% external quantum efficiency in blue, above 30% external quantum efficiency in green, and close to 18% external quantum efficiency in red devices. Therefore, TADF organic light-emitting diodes could potentially be substituted for high-efficiency phosphorescent organic light-emitting diodes. In this work, we reviewed molecular design strategies of organic-based TADF emitters by classifying them into several categories depending on the material parameters required for the TADF emitters. In addition, we proposed a future development direction of TADF emitters to make them competitive with phosphorescent emitters.
Soybean paste is manufactured through microbial fermentation and may become contaminated with aflatoxins. Herein, we conducted nationwide large-scale monitoring (n = 1436) over three years ...(2018–2020) to investigate aflatoxin levels according to geographic, demographic, manufacturing, quality factors, and risk characteristics of homemade soybean paste produced through fermentation. The mean level of total aflatoxins was 5.88 μg/kg (range, 0.01–281.92), with the most common contaminating type being the B type. Aflatoxin levels significantly differed according to the region, age of the manufacturer, type of starter used, and the amino-type nitrogen content and pH of the homemade soybean paste (p < 0.05). Aflatoxin levels was significantly higher when starters were manufactured using the traditional method (inoculation with a naturally occurring strain in the surrounding environment). The aflatoxin exposure level estimated through the average intake of homemade soybean paste in all age groups was 0.1012 ng/kg body weight/day. The risk assessment for the genotoxic and carcinogenic potential of aflatoxins using the margin of exposure approach revealed values of 3705–3954 for average intake of homemade soybean paste, indicating public health concern. These results suggest that follow-up studies and safety management strategies are needed to reduce aflatoxin levels in homemade soybean paste.
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•Fermented soybean food has excellent nutritional value.•Traditional soybean paste is manufactured using microbes in the environment.•Contamination and risk characteristics of homemade soybean paste were evaluated.•Aflatoxin level was higher when starters were prepared with the traditional method.•Safety management is needed to reduce aflatoxin levels in homemade soybean paste.
Novel and selective detection of Tabun mimics Jang, Yoon Jeong; Tsay, Olga G; Murale, Dhiraj P ...
Chemical communications (Cambridge, England),
01/2014, Volume:
50, Issue:
56
Journal Article
Peer reviewed
Detection of nerve agent-related molecules based on BODIPY-salicylaldehyde oxime conjugation was studied. Fluorescence intensity of the B-SAL-OXIME species increases in the presence of DECP, whereas ...it decreases in the presence of DCP and DEMP (limit of detection = 997 nM). Benzonitrile formation in the novel fluorescent B-SAL-OXIME system was elucidated using model substrates.
Next-generation battery development necessitates the coevolution of liquid electrolyte and electrode chemistries, as their erroneous combinations lead to battery failure. In this regard, priority ...should be given to the alleviation of the volumetric stress experienced by silicon and lithium-metal anodes during cycling and the mitigation of other problems hindering their commercialization. This review summarizes the advances in sacrificial compound-based volumetric stress-adaptable interfacial engineering, which has primarily driven the development of liquid electrolytes for high-performance lithium batteries. Besides, we discuss how the regulation of lithium-ion solvation structures helps expand the range of electrolyte formulations and thus enhance the quality of solid electrolyte interphases (SEIs), improve lithium-ion desolvation kinetics, and realize longer-lasting SEIs on high-capacity anodes. The presented insights are expected to inspire the design and synthesis of next-generation electrolyte materials and accelerate the development of advanced electrode materials for industrial battery applications.
This review comprehensively summarizes the key features of existing liquid electrolyte formulations for Si and Li metal anodes and proposes design rules for advanced liquid electrolyte chemistry.
The complexity of the pathogenic cascade in lysosomal storage disorders suggests that combination therapy will be needed to target various aspects of pathogenesis. The standard of care for Pompe ...disease (glycogen storage disease type II), a deficiency of lysosomal acid alpha glucosidase, is enzyme replacement therapy (ERT). Many patients have poor outcomes due to limited efficacy of the drug in clearing muscle glycogen stores. The resistance to therapy is linked to massive autophagic buildup in the diseased muscle. We have explored two strategies to address the problem. Genetic suppression of autophagy in muscle of knockout mice resulted in the removal of autophagic buildup, increase in muscle force, decrease in glycogen level, and near-complete clearance of lysosomal glycogen following ERT. However, this approach leads to accumulation of ubiquitinated proteins, oxidative stress, and exacerbation of muscle atrophy. Another approach involves AAV-mediated TSC knockdown in knockout muscle leading to upregulation of mTOR, inhibition of autophagy, reversal of atrophy, and efficient cellular clearance on ERT. Importantly, this approach reveals the possibility of reversing already established autophagic buildup, rather than preventing its development.
Conventional enzyme replacement therapy for Pompe disease is of limited effectiveness at least in part because of the presence of large areas of autophagic debris in the diseased muscle. Here, Lim et al. explore pros and cons of different ways to manipulate autophagic process in order to improve the therapy. The authors also investigate protein synthesis and degradation in Pompe muscle and suggest a strategy to improve altered proteostasis.
Green tea is rich in polyphenol flavonoids including catechins. Epigallocatechin 3-gallate (EGCG) is the most abundant and potent green tea catechin. EGCG has been extensively studied for its ...beneficial health effects as a nutriceutical agent. Based upon its chemical structure, EGCG is often classified as an antioxidant. However, treatment of cells with EGCG results in production of hydrogen peroxide and hydroxyl radicals in the presence of Fe (III). Thus, EGCG functions as a pro-oxidant in some cellular contexts. Recent investigations have revealed many other direct actions of EGCG that are independent from anti-oxidative mechanisms. In this review, we discuss these novel molecular mechanisms of action for EGCG. In particular, EGCG directly interacts with proteins and phospholipids in the plasma membrane and regulates signal transduction pathways, transcription factors, DNA methylation, mitochondrial function, and autophagy to exert many of its beneficial biological actions.
Alzheimer's disease (AD) is characterized by the accumulation of amyloid plaques and neurofibrillary tangles accompanied by cognitive dysfunction. The aim of the present study was to elucidate ...preventive and therapeutic potential of stem cells for AD. Among stem cells, autologous human adipose-derived stem cells (hASCs) elicit no immune rejection responses, tumorigenesis, or ethical problems. We found that intravenously transplanted hASCs passed through the BBB and migrated into the brain. The learning, memory and pathology in an AD mouse model (Tg2576) mice greatly improved for at least 4 months after intravenous injection of hASC. The number of amyloid plaques and Aβ levels decreased significantly in the brains of hASC-injected Tg mice compared to those of Tg-sham mice. Here, we first report that intravenously or intracerebrally transplanted hASCs significantly rescues memory deficit and neuropathology, in the brains of Tg mice by up-regulating IL-10 and VEGF and be a possible use for the prevention and treatment of AD.
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