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.
Atopic dermatitis (AD) is a chronic inflammatory skin disease with specific immune and inflammatory mechanisms. Atopy is among the major features of the diagnosis criteria for AD but is not an ...essential feature. Thus, patients diagnosed with AD can be atopic or non-atopic. This review focuses on the role of IgE, mast cells, and eosinophils in the pathogenesis of AD. The known functions of IgE in allergic inflammation suggest that IgE and IgE-mediated mast cell and eosinophil activation contribute to AD, but direct evidence supporting this is scarce. The level of IgE (thus the degree of allergic sensitization) is associated with severity of AD and contributed by abnormality of skin barrier, a key feature of AD. The function of IgE in development of AD is supported by the beneficial effect of anti-IgE therapy in a number of clinical studies. The role of mast cells in AD is suggested by the increase in the mast cell number and mast cell activation in AD lesions and the association between mast cell activation and AD. It is further suggested by their role in mouse models of AD as well as by the effect of therapeutic agents for AD that can affect mast cells. The role of eosinophils in AD is suggested by the presence of eosinophilia in AD patients and eosinophil infiltrates in AD lesions. It is further supported by information that links AD to cytokines and chemokines associated with production, recruitment, and activation of eosinophils.
Introduction
Severe spinal cord injury results in the loss of neurons in the relatively intact spinal cord below the injury area and skeletal muscle atrophy in the paralyzed limbs. These pathological ...processes are significant obstacles for motor function reconstruction.
Objective
We performed tail nerve electrical stimulation (TNES) to activate the motor neural circuits below the injury site of the spinal cord to elucidate the regulatory mechanisms of the excitatory afferent neurons in promoting the reconstruction of locomotor function.
Methods
Eight days after T10 spinal cord transection in rats, TNES was performed for 7 weeks. Behavioral scores were assessed weekly. Electrophysiological tests and double retrograde tracings were performed at week 8.
Results
After 7 weeks of TNES treatment, there was restoration in innervation, the number of stem cells, and mitochondrial metabolism in the rats' hindlimb muscles. Double retrograde tracings of the tail nerve and sciatic nerve further confirmed the presence of synaptic connections between the tail nerve and central pattern generator (CPG) neurons in the lumbar spinal cord, as well as motor neurons innervating the hindlimb muscles.
Conclusion
The mechanisms of TNES induced by the stimulation of primary afferent nerve fibers involves efficient activation of the motor neural circuits in the lumbosacral segment, alterations of synaptic plasticity, and the improvement of muscle and nerve regeneration, which provides the structural and functional foundation for the future use of cutting‐edge biological treatment strategies to restore voluntary movement of paralyzed hindlimbs.
The specific neural pathway and the mechanism of activation in the spinal cord CPG and effects on the motor neural circuits during TNES treatment.
...developmental stages of B cells, that is B220+CD43+IgM−IgD− (pro‐B), B220+CD43−IgM−IgD− (pre‐B), B220+CD43−IgM+IgD− (immature B) and B220+CD43−IgM+IgD+ (mature B), were detected in mouse BM, ...intestinal lamina propria (LPL) and Peyer's patches (PPs) by flow cytometry. ...the expression levels of CD40, CD80 and MHC‐Ⅱ on B cells were detected in mouse SPL, MLN and PPs. ...we examined the Secretory Immunoglobulin A (SIgA) level in intestinal lavage fluid and serum IgM, IgA and Immunoglobulin G (IgG) by ELISA. ...LGG intervention can promote the development and maturation of B lymphocytes, enhance the activation and antigen‐presentation ability of B lymphocytes, and regulate the secretion of immunoglobulin by B lymphocytes. ...LGG can regulate the mucosal immunity and humoural immunity of mice.
Abstract
While glycans are generally displayed on the cell surface or confined within the lumen of organelles, they can become exposed to the cytosolic milieu upon disruption of organelle membrane by ...various stresses or pathogens. Galectins are a family of β-galactoside-binding animal lectins synthesized and predominantly localized in the cytosol. Recent research indicates that some galectins may act as “danger signal sensors” by detecting unusual exposure of glycans to the cytosol. Galectin-8 was shown to promote antibacterial autophagy by recognizing host glycans on ruptured vacuolar membranes and interacting with the autophagy adaptor protein NDP52. Galectin-3 also accumulates at damaged phagosomes containing bacteria; however, its functional consequence remains obscure. By studying mouse macrophages infected with Listeria monocytogenes (LM), we showed that endogenous galectin-3 protects intracellular LM by suppressing the autophagic response through a host N-glycan-dependent mechanism. Knock out of the galectin-3 gene resulted in enhanced LC3 recruitment to LM and decreased bacterial replication, a phenotype recapitulated when Galectin-8-deficient macrophages were depleted of N-glycans. Moreover, we explored the concept that alterations in cell surface glycosylation by extracellular factors can be deciphered by cytosolic galectins during the process of phagocytosis/endocytosis, followed by rupture of phagosomal/endosomal membrane. Notably, treatment of cells with sialidase, which removes sialic acid from glycans, resulted in increased galectin-3 accumulation and decreased galectin-8 recruitment at damaged phagosomes, and led to a stronger anti-autophagic response. Our findings demonstrate that cytosolic galectins may sense changes in glycosylation at the cell surface and modulate cellular response through differential recognition of glycans on ruptured phagosomal membranes.
Galectin-3 is absent in resting CD4⁺ and CD8⁺ T cells but is inducible by various stimuli. These include viral transactivating factors, T-cell receptor (TCR) ligation, and calcium ionophores. In ...addition, galectin-3 is constitutively expressed in human regulatory T cells and CD4⁺ memory T cells. Galectin-3 exerts extracellular functions because of its lectin activity and recognition of cell surface and extracellular matrix glycans. These include cell activation, adhesion, induction of apoptosis, and formation of lattices with cell surface glycoprotein receptors. Formation of lattices can result in restriction of receptor mobility and cause attenuation of receptor functions. Consistent with the presence of galectin-3 in intracellular locations, several functions have been described for this protein inside T cells. These include inhibition of apoptosis, promotion of cell growth, and regulation of TCR signal transduction. Studies of cell surface glycosylation have led to convergence of glycobiology and galectin biology and provided new clues on how galectin-3 may participate in the regulation of cell surface receptor activities. The rapid expansion of the field of galectin research has positioned galectin-3 as a key regulator in T-cell functions.
Conservation tillage can improve soil physical structure and water storage, protect moisture, and increase crop yield. However, the long-term adoption of a single tillage method may have some adverse ...effects on soil and ecological environment, although crop yields have increased. Through informed allocation of soil tillage techniques, the combination and configuration of soil tillage measures, such as rotary tillage, subsoiling, and no tillage may reduce the shortcomings of traditional long-term farming. To explore the long-term production mode suitable for production of maize in the loess dryland area, a long-term experiment was conducted in Fuping County, Shaanxi Province, from 2013 to 2018. Six farming modes were used in the experiment: no tillage/subsoiling (N ↔ S), subsoiling/rotary tillage (S ↔ R), rotary tillage/no tillage (R ↔ N), continuous no tillage (N ↔ N), continuous subsoiling (S ↔ S), and continuous rotary tillage (R ↔ R). The changes in soil physical and chemical properties, soil water use patterns, soil water storage, conservation effects during the fallow and growth period, and the effects on farmland yield increase were analyzed. The results showed that rotary tillage can effectively improved soil structure and reduced soil bulk density, where N ↔ S treatment soil bulk density is low and in 0-60 cm soil layer averaged 1.31 g/cm
. Different tillage treatments could be used during the fallow period to store additional soil moisture: the N ↔ S treatment showed good water storage effect. Compared to traditional tillage, different tillage methods provided better soil moisture conditions for crops during the growth period, where N ↔ S treatment showed good soil moisture status during the growth period of spring maize. Among all the treatments, N ↔ S treatment effectively increased the organic carbon storage in the 0-60 cm soil layer, which was 54.3 t/hm
. Compared with traditional tillage, different tillage treatments effectively increased plant height and dry matter accumulation of spring maize, where N ↔ S treatment was found to be the best. Compared with the traditional rotary tillage model, the N ↔ S treatment significantly increased crop yield and water use efficiency (WUE) in continuous cropping fields of corn, the average yield of spring corn was 9340.2 kg/hm
, and the average WUE was 22.9 kg/(hm
·mm). In summary, for long-term sustainable development, the N ↔ S model is the best rotational tillage mode for continuous maize cropping in loess soil.
The Asian honey bee
is a valuable biological resource insect that plays an important role in the ecological environment and agricultural economy. The composition of the gut microbiota has a great ...influence on the health and development of the host. However, studies on the insect gut microbiota are rarely reported, especially studies on the dynamic succession of the insect gut microbiota. Therefore, this study used high-throughput sequencing technology to sequence the gut microbiota of
at different developmental stages (0 days post emergence (0 dpe), 1 dpe, 3 dpe, 7 dpe, 12 dpe, 19 dpe, 25 dpe, 30 dpe, and 35 dpe). The results of this study indicated that the diversity of the gut microbiota varied significantly at different developmental stages (ACE,
= 0.045; Chao1,
= 0.031; Shannon,
= 0.0019; Simpson,
= 0.041). In addition, at the phylum and genus taxonomic levels, the dominant constituents in the gut microbiota changed significantly at different developmental stages. Our results also suggest that environmental exposure in the early stages of development has the greatest impact on the gut microbiota. The results of this study reveal the general rule of gut microbiota succession in the
life cycle. This study not only deepens our understanding of the colonization pattern of the gut microbiota in workers but also provides more comprehensive information for exploring the colonization of the gut microbiota in insects and other animals.
Highly pathogenic avian influenza A H5N1 virus causes pneumonia and acute respiratory distress syndrome in humans. Virus-induced excessive inflammatory response contributes to severe disease and high ...mortality rates. Galectin-3, a β-galactoside-binding protein widely distributed in immune and epithelial cells, regulates various immune functions and modulates microbial infections. Here, we describe galectin-3 up-regulation in mouse lung tissue after challenges with the H5N1 influenza virus. We investigated the effects of endogenous galectin-3 on H5N1 infection and found that survival of galectin-3 knockout (Gal-3KO) mice was comparable with wild-type (WT) mice after infections. Compared with infected WT mice, infected Gal-3KO mice exhibited less inflammation in the lungs and reduced IL-1β levels in bronchoalveolar lavage fluid. In addition, the bone marrow–derived macrophages (BMMs) from Gal-3KO mice exhibited reduced oligomerization of apoptosis-associated speck-like proteins containing caspase-associated recruitment domains and secreted less IL-1β compared with BMMs from WT mice. However, similar levels of the inflammasome component of nucleotide oligomerization domain–like receptor protein 3 (NLRP3) were observed in two genotypes of BMMs. Co-immunoprecipitation data indicated galectin-3 and NLRP3 interaction in BMMs infected with H5N1. An association was also observed between galectin-3 and NLRP3/apoptosis-associated speck-like proteins containing caspase-associated recruitment domain complex. Combined, our results suggest that endogenous galectin-3 enhances the effects of H5N1 infection by promoting host inflammatory responses and regulating IL-1β production by macrophages via interaction with NLRP3.
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