Abstract
Metabolite alteration has been associated with the pathogenesis of inflammatory bowel disease (IBD), including colitis. Mannose, a natural bioactive monosaccharide that is involved in ...metabolism and synthesis of glycoproteins, exhibits anti-inflammatory and anti-oxidative activities. We show here that the circulating level of mannose is increased in patients with IBD and mice with experimental colitis. Mannose treatment attenuates intestinal barrier damage in two mouse colitis models, dextran sodium sulfate (DSS)-induced colitis and spontaneous colitis in
IL-10
-deficient mice. We demonstrate that mannose treatment enhanced lysosomal integrity and limited the release of cathepsin B, preventing mitochondrial dysfunction and myosin light chain kinase (MLCK)-induced tight junction disruption in the context of intestinal epithelial damage. Mannose exerts a synergistic therapeutic effect with mesalamine on mouse colitis. Cumulatively, the results indicate that mannose supplementation may be an optional approach to the treatment of colitis and other diseases associated with intestinal barrier dysfunction.
Mannan-binding lectin (MBL) is a pattern-recognition molecule that plays a crucial role in innate immunity. MBL deficiency correlates with an increased risk of chronic kidney disease (CKD). However, ...the molecular mechanisms are not fully defined. Here, we established a CKD model in wild-type (WT) and MBL-deficient (MBL−/−) mice via unilateral ureteral obstruction (UUO). The result showed that MBL deficiency aggravated the pathogenesis of renal fibrosis in CKD mice. Strikingly, the in vivo macrophage depletion investigation revealed that macrophages play an essential role in the MBL-mediated suppression of renal fibrosis. We found that MBL limited the progression of macrophage-to-myofibroblast transition (MMT) in kidney tissues of UUO mice. Further in vitro study showed that MBL−/− macrophages exhibited significantly increased levels of fibrotic-related molecules compared with WT cells upon transforming growth factor beta (TGF-β) stimulation. We demonstrated that MBL inhibited the MMT process by suppressing the production of matrix metalloproteinase 9 (MMP-9) and activation of Akt signaling. In summary, our study revealed an expected role of MBL on macrophage transition during renal fibrosis, thus offering new insight into the potential of MBL as a therapeutic target for CKD.
Mannose is a unique natural sugar that can be found in a variety of fruits and vegetables. During the past decades, mannose has been reported to be effective in promoting immune tolerance and ...suppressing inflammatory diseases. Metabolic dysfunction and altered inflammation have clear implications for the development and progression of inflammatory diseases. Herein, we intended to reveal the molecular mechanism of mannose in protecting against intestinal epithelial damage in experimental colitis. We showed that mannose treatment significantly attenuated dextran sodium sulfate (DSS)-induced intestinal barrier damage. The AMPK pathway was responsible for the mannose-mediated protective effect in DSS-induced intestinal epithelial damage. Mechanistically, mannose promoted the axis inhibition protein (AXIN)-based AMPK activation, thereby preventing mitochondrial dysfunction and tight junction disruption in response to the DSS challenge. Cumulatively, the results indicate the use of mannose as a novel approach to treat IBD and other diseases involving tight junction dysfunction. The therapeutic effect of mannose is related to its regulatory function in AMPK pathway activation.
Mannan-binding lectin (MBL), a soluble pattern recognition molecule in the innate immune system, is reported to be associated with the function of immune cells. Myeloid-derived suppressor cells ...(MDSCs) are mainly characterized by immunosuppressive activities involving several inflammatory diseases such as cancer, infection, and arthritis. Some of the factors inducing their apoptosis are known, however, mechanisms have not been identified. The underlying impact of MBL on the MDSCs especially under inflammatory conditions remains unknown. This study was designed to investigate whether MBL affects MDSCs survival during inflammation conditions.
WT and MBL-deficient (MBL
) mice were induced on day 0 of the experiment by subcutaneous injection of complete Freund's adjuvant and then injected with incomplete Freund's adjuvant into the knee joint space under general anesthesia on day 14 to induce inflammatory arthritis. The proportions of MDSCs in the spleen and blood and the serum level of the inflammatory cytokines were measured. In vitro study, MDSCs were isolated from the bone marrow of WT and MBL
mice and cultured in the presence of interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) for 5 days with or without tumor necrosis factor-alpha (TNF-α).
After adjuvant treatment, MBL
mice had a significantly lower frequency of MDSCs as well as elevated serum inflammatory cytokines levels compared to WT mice. MBL deficiency markedly inhibited the MDSCs frequency from mice bone marrow induced by IL-6 and GM-CSF in the presence of TNF-α
. Mechanistic studies established that MBL inhibited MDSCs apoptosis via down-regulation of TNF-α/tumor necrosis factor-alpha receptor 1 (TNFR1) signaling pathway and subsequent caspase 3-dependent manner.
Mannan-binding lectin deficiency inhibits myeloid-derived suppressor cells expansion via modulating TNF-α triggered apoptosis.
β-TCP ceramics drug carrier was first prepared and characterized. SEM showed that β-TCP carrier was in porous amorphous structure with diameters around 10 μm. The physical properties including ...apparent porosity, volume-weight, tensile strength and the permeability were measured and the results indicated those properties fit the clinical usage of β-TCP drug carrier. Furthermore, drug release experiment in vitro showed that the carrier could prolong drug release in simulated body fluid which provides basis for the clinical use of β-TCP ceramics as drug carrier.
β-tricalcium phosphate （β-TCP） powder and Na20-CaO-MgO-P205 glass binder were synthesized and mixed, and then the biodegradable porous calcium phosphate ceramics were successfully prepared by foaming ...and sintering at 850℃. The as-prepared ceramics possess a high porosity with partial three-dimension interconnected macro- and micro-pores. As in vitro experiment testified, the calcium phosphate ceramics （CPCs） has good degradability.
The basolateral amygdala (BLA) and ventral hippocampal CA1 (vCA1) are cellularly and functionally diverse along their anterior-posterior and superficial-deep axes. Here, we find that anterior BLA ...(aBLA) and posterior BLA (pBLA) innervate deep-layer calbindin1-negative (Calb1-) and superficial-layer calbindin1-positive neurons (Calb1+) in vCA1, respectively. Photostimulation of pBLA-vCA1 inputs has an anxiolytic effect in mice, promoting approach behaviours during conflict exploratory tasks. By contrast, stimulating aBLA-vCA1 inputs induces anxiety-like behaviour resulting in fewer approaches. During conflict stages of the elevated plus maze task vCA1
neurons are preferentially activated at the open-to-closed arm transition, and photostimulation of vCA1
neurons at decision-making zones promotes approach with fewer retreats. In the APP/PS1 mouse model of Alzheimer's disease, which shows anxiety-like behaviour, photostimulating the pBLA-vCA1
circuit ameliorates the anxiety in a Calb1-dependent manner. These findings suggest the pBLA-vCA1
circuit from heterogeneous BLA-vCA1 connections drives approach behaviour to reduce anxiety-like behaviour.
The ability of light beams to rotate nano-objects has important applications in optical micromachines and biotechnology. However, due to the diffraction limit, it is challenging to rotate ...nanoparticles at subwavelength scale. Here, we propose a method to obtain controlled fast orbital rotation (i.e., circumgyration) at deep subwavelength scale, based on the nonlinear optical effect rather than sub-diffraction focusing. We experimentally demonstrate rotation of metallic nanoparticles with orbital radius of 71 nm, to our knowledge, the smallest orbital radius obtained by optical trapping thus far. The circumgyration frequency of particles in water can be more than 1 kHz. In addition, we use a femtosecond pulsed Gaussian beam rather than vortex beams in the experiment. Our study provides paradigms for nanoparticle manipulation beyond the diffraction limit, which will not only push toward possible applications in optically driven nanomachines, but also spur more fascinating research in nano-rheology, micro-fluid mechanics and biological applications at the nanoscale.
Epididymal white adipose tissue (eWAT) secretes an array of cytokines to regulate the metabolism of organs and tissues in high-fat diet (HFD)-induced obesity, but its effects on bone metabolism are ...not well understood. Here, we report that macrophages in eWAT are a main source of osteopontin, which selectively circulates to the bone marrow and promotes the degradation of the bone matrix by activating osteoclasts, as well as modulating bone marrow-derived macrophages (BMDMs) to engulf the lipid droplets released from adipocytes in the bone marrow of mice. However, the lactate accumulation induced by osteopontin regulation blocks both lipolysis and osteoclastogenesis in BMDMs by limiting the energy regeneration by ATP6V0d2 in lysosomes. Both surgical removal of eWAT and local injection of either clodronate liposomes (for depleting macrophages) or osteopontin-neutralizing antibody show comparable amelioration of HFD-induced bone loss in mice. These results provide an avenue for developing therapeutic strategies to mitigate obesity-related bone disorders.
Fabric computer-aided design has become a hot research topic in recent years. The main objective of this research is to innovate a method of design, simulation and virtual display for weft-knitted ...striped jacquard fabrics. Preferentially, the fabric design and simulation models were established and the virtual yarns are intermeshed by connecting each control point of the loops to generate the structural simulation. The simulated image was captured as the texture image. The virtual display method of the garment based on texture mapping was mainly studied and innovated. Texture matching was realized based on the two-dimensional garment piece models and the vertices texture coordinates of the three-dimensional garment models were reset, then the three-dimensional garment virtual display was realized according to the mapping relationship between the triangles. During this process, the position of the texture can be dynamically designed and adjusted to achieve the desired effect. This research introduced the design of four kinds of striped fabrics and illustrated the corresponding simulation and virtual display effect to verify the feasibility of the method. The analysis of simulation efficiency reveals that the method responds quickly and has favorable adaptability to diverse patterns and models. The research provides a new idea for the computer-aided design of knitted fabrics and promotes the development of personalized garment customization.
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