The galectin family consists of carbohydrate (glycan) binding proteins that are expressed by a wide variety of cells and bind to galactose-containing glycans. Galectins can be located in the nucleus ...or the cytoplasm, or can be secreted into the extracellular space. They can modulate innate and adaptive immune cells by binding to glycans on the surface of immune cells or intracellularly via carbohydrate-dependent or carbohydrate-independent interactions. Galectins expressed by immune cells can also participate in host responses to infection by directly binding to microorganisms or by modulating antimicrobial functions such as autophagy. Here we explore the diverse ways in which galectins have been shown to impact immunity and discuss the opportunities and challenges in the field.
L-Ergothioneine (EGT) is a natural antioxidant derived from microorganisms, especially in edible mushrooms. EGT is found to be highly accumulated in tissues that are susceptible to oxidative damage, ...and it has attracted extensive attention due to its powerful antioxidant activity and the tight relationships of this natural product with various oxidative stress-related diseases. Herein, we 1) introduce the biological source and
distribution of EGT; 2) review the currently available evidence concerning the relationships of EGT with diabetes, ischemia-reperfusion injury-related diseases like cardiovascular diseases and liver diseases, neurodegenerative diseases, and other diseases pathogenically associated with oxidative stress; 3) summarize the potential action mechanisms of EGT against these diseases; 4) discuss the advantages of EGT over other antioxidants; and 5) also propose several future research perspectives for EGT. These may help to promote the future application of this attractive natural antioxidant.
Galectins, β‐galactoside‐binding animal lectins, are differentially expressed by various immune cells as well as a wide range of other cell types. Extracellularly, galectins are able to exhibit ...bivalent or multivalent interactions with cell‐surface glycans on various immune cells and exert various effects. These include cytokine and mediator production, cell adhesion, apoptosis, and chemoattraction. In addition, they can form lattices with cell‐surface glycoprotein receptors, resulting in modulation of receptor functions, including clustering and endocytosis. Intracellularly, galectins can participate in signaling pathways and modulate biologic responses. These include apoptosis, cell differentiation, and cell migration. Thus, a large body of literature indicates that galectins play important roles in the immune and inflammatory responses through regulating the homeostasis and functions of immune cells. The use of mice deficient in individual galectins has provided additional evidence for the contributions of these proteins to these responses. Current research indicates that galectins play important roles in the development of acute inflammation as well as chronic inflammation associated with allergies, autoimmune diseases, atherosclerosis, infectious processes, and cancer. Thus, recombinant proteins or specific galectin inhibitors may be used as therapeutic agents for inflammatory diseases.
Huntington's disease (HD) is a neurodegenerative disorder that manifests with movement dysfunction. The expression of mutant Huntingtin (mHTT) disrupts the functions of brain cells. Galectin-3 (Gal3) ...is a lectin that has not been extensively explored in brain diseases. Herein, we showed that the plasma Gal3 levels of HD patients and mice correlated with disease severity. Moreover, brain Gal3 levels were higher in patients and mice with HD than those in controls. The up-regulation of Gal3 in HD mice occurred before motor impairment, and its level remained high in microglia throughout disease progression. The cell-autonomous up-regulated Gal3 formed puncta in damaged lysosomes and contributed to inflammation through NFκB- and NLRP3 inflammasome-dependent pathways. Knockdown of Gal3 suppressed inflammation, reduced mHTT aggregation, restored neuronal DARPP32 levels, ameliorated motor dysfunction, and increased survival in HD mice. Thus, suppression of Gal3 ameliorates microglia-mediated pathogenesis, which suggests that Gal3 is a novel druggable target for HD.
•All ELISA kits evaluated could effectively quantify milk protein in unheated oil.•Frying reduced the level of milk protein detected in the oil by all methods.•Depending on the test kits, ...preextraction may improve or lower detection in fried oil.•Very little protein could be detected in oil fried at typical frying temperature.•Impact of heat should be considered when ELISA results are used for risk assessment.
Milk is a common ingredient in fried foods. Allergen cross-contact can occur through the reuse of frying oil. To enable assessment of the allergy risk of reused oil, methods for quantification of milk protein in oil are needed. This study evaluated four commercial ELISA test kits in comparison with the 660 nm total protein assay for the detection of milk protein in oil after frying. Corn oil spiked with nonfat or whole milk powder were fried at 150 °C or 180 °C for 3 min and were analyzed by ELISA kits either directly or after preextraction with phosphate-buffered saline containing 0.05% Tween (PBST). All four ELISA kits performed well in quantifying milk protein in unheated oil, achieving normalized recoveries of 72.1–115.9% compared with that determined in reference solutions (PBST spiked with nonfat or whole milk powder, 100%). Frying lowered the amount of protein detected, but the extent of reduction differed between test kits. In nonfat milk powder-spiked oil fried at 150 °C, normalized recoveries determined by Veratox Total Milk and BioKits BLG Assay (49.9% and 43.6%, respectively) were higher than that determined by the 660 nm assay (25.4%). Normalized recoveries determined by ELISA Systems Casein and Beta-Lactoglobulin (BLG) kits were substantially lower (9.7% and 2.4%, respectively). In samples fried under typical frying temperature (180 °C), very little protein (0.1–7.4%) was detected. Inclusion of PBST preextraction improved the detection of the two test kits targeting BLG but lowered the level of protein detected by Veratox and ELISA Systems Casein in fried samples. Overall, the ELISA kits evaluated could effectively quantify milk protein in unheated oil without the need to remove the oil phase prior to analysis. Heat treatment was the key factor negatively affecting protein quantitation. Such impact needs to be considered when ELISA test results are used for assessing the allergy risk of reused frying oil.
The tumor microenvironment is highly complex, and immune escape is currently considered an important hallmark of cancer, largely contributing to tumor progression and metastasis. Named for their ...capability of killing target cells autonomously, natural killer (NK) cells serve as the main effector cells toward cancer in innate immunity and are highly heterogeneous in the microenvironment. Most current treatment options harnessing the tumor microenvironment focus on T cell-immunity, either by promoting activating signals or suppressing inhibitory ones. The limited success achieved by T cell immunotherapy highlights the importance of developing new-generation immunotherapeutics, for example utilizing previously ignored NK cells. Although tumors also evolve to resist NK cell-induced cytotoxicity, cytokine supplement, blockade of suppressive molecules and genetic engineering of NK cells may overcome such resistance with great promise in both solid and hematological malignancies. In this review, we summarized the fundamental characteristics and recent advances of NK cells within tumor immunometabolic microenvironment, and discussed potential application and limitations of emerging NK cell-based therapeutic strategies in the era of presicion medicine.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Intracellular galectins are carbohydrate-binding proteins capable of sensing and repairing damaged lysosomes. As in the physiological conditions glycosylated moieties are mostly in the lysosomal ...lumen but not cytosol, it is unclear whether galectins reside in lysosomes, bind to glycosylated proteins, and regulate lysosome functions. Here, we show in gut epithelial cells, galectin-9 is enriched in lysosomes and predominantly binds to lysosome-associated membrane protein 2 (Lamp2) in a Asn(N)-glycan dependent manner. At the steady state, galectin-9 binding to glycosylated Asn
of Lamp2 is essential for functionality of lysosomes and autophagy. Loss of N-glycan-binding capability of galectin-9 causes its complete depletion from lysosomes and defective autophagy, leading to increased endoplasmic reticulum (ER) stress preferentially in autophagy-active Paneth cells and acinar cells. Unresolved ER stress consequently causes cell degeneration or apoptosis that associates with colitis and pancreatic disorders in mice. Therefore, lysosomal galectins maintain homeostatic function of lysosomes to prevent organ pathogenesis.
Antibodies are an important component in host immune responses to viral pathogens. Because of their unique maturation process, antibodies can evolve to be highly specific to viral antigens. ...Physicians and researchers have been relying on such high specificity in their quest to understand host-viral interaction and viral pathogenesis mechanisms and to find potential cures for viral infection and disease. With more than 60 recombinant monoclonal antibodies developed for human use in the last 20 years, monoclonal antibodies are now considered a viable therapeutic modality for infectious disease targets, including newly emerging viral pathogens such as Ebola representing heightened public health concerns, as well as pathogens that have long been known, such as human cytomegalovirus. Here, we summarize some recent advances in identification and characterization of monoclonal antibodies suitable as drug candidates for clinical evaluation, and review some promising candidates in the development pipeline.
Recent studies have shown that a carbohydrate-binding protein, galectin-3, is a novel pro-angiogenic molecule. The mechanism by which galectin-3 promotes angiogenesis remains unknown. We demonstrate ...here that galectin-3 is a mediator of vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (bFGF)-mediated angiogenic response. Angiogenesis assays revealed that galectin-3 inhibitors, beta-lactose and dominant-negative galectin-3, reduce VEGF- and bFGF-mediated angiogenesis in vitro and that VEGF- and bFGF-mediated angiogenic response is reduced in galectin-3 knockdown cells and Gal3(-/-) animals. Integrin alphavbeta3 was identified as the major galectin-3-binding protein and anti-alphav, -beta3, and -alphavbeta3 integrin function-blocking antibodies significantly inhibited the galectin-3-induced angiogenesis. Furthermore, galectin-3 promoted the clustering of integrin alphavbeta3 and activated focal adhesion kinase. Knockdown of GnTV, an enzyme that synthesizes high-affinity glycan ligands for galectin-3, substantially reduced: (a) complex N-glycans on alphavbeta3 integrins and (b) VEGF- and bFGF-mediated angiogenesis. Collectively, these data suggest that galectin-3 modulates VEGF- and bFGF-mediated angiogenesis by binding via its carbohydrate recognition domain, to the GnTV synthesized N-glycans of integrin alphavbeta3, and subsequently activating the signaling pathways that promote the growth of new blood vessels. These findings have broad implications for developing novel, carbohydrate-based therapeutic agents for inhibition of angiogenesis.
Microbial contamination of sprouts by Salmonella and Escherichia coli O157 : H7 has been a common cause of foodborne diseases and a continuing challenge to the sprout industry. Seed disinfection ...treatment has been recommended as a major intervention step in a multihurdle approach to reduce the risk of illness associated with contaminated sprouts. U.S. Food and Drug Administration cited 20000 ppm calcium hypochlorite as an example treatment in its recommendation for seed treatment and this treatment has been considered the reference standard for seed disinfection treatment for over a decade. However, promising new disinfection treatments have emerged in recent years. In this study, we summarized published data and compared the efficacies of different disinfection methods in the reduction of microbial contamination on seeds. Our findings suggest that while biological interventions such as competitive exclusion and certain chemical treatments appear to be similar to 20000 ppm calcium hypochlorite for seed disinfection, physical methods especially high pressure may be more effective than the reference standard regardless of the type of bacteria or seed. The combination of 2 or more treatments, sequentially or simultaneously, may further improve disinfection results. Since treatments with high levels of chemical disinfectants, especially 20000 ppm calcium hypochlorite, can pose environmental and worker safety risks, alternative intervention approaches should be considered. Additional studies to confirm the greater efficacy of certain physical and combined seed disinfection treatments and to identify other effective management strategies are needed to further improve sprout safety.
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