ABSTRACT
Regulatory T (Treg) cells are essential for maintenance of immune homeostasis. Here we found that hydrogen sulfide (H2S) was required for Foxp3(+) Treg cell differentiation and function and that H2S deficiency led to systemic autoimmune disease. H2S maintained expression of methylcytosine dioxygenases Tet1 and Tet2 by sulfhydrating nuclear transcription factor Y subunit beta (NFYB) to facilitate its binding to Tet1 and Tet2 promoters. Transforming growth factor-ß (TGF-ß)-activated Smad3 and interleukin-2 (IL-2)-activated Stat5 facilitated Tet1 and Tet2 binding to Foxp3. Tet1 and Tet2 catalyzed conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in Foxp3 to establish a Treg-cell-specific hypomethylation pattern and stable Foxp3 expression. Consequently, Tet1 and Tet2 deletion led to Foxp3 hypermethylation, impaired Treg cell differentiation and function, and autoimmune disease. Thus, H2S promotes Tet1 and Tet2 expression, which are recruited to Foxp3 by TGF-ß and IL-2 signaling to maintain Foxp3 demethylation and Treg-cell-associated immune homeostasis.
Subject(s)
Colitis/immunology , DNA-Binding Proteins/metabolism , Forkhead Transcription Factors/metabolism , Hydrogen Sulfide/metabolism , Proto-Oncogene Proteins/metabolism , T-Lymphocytes, Regulatory/immunology , Adoptive Transfer , Animals , CCAAT-Binding Factor/metabolism , Cell Differentiation/genetics , Colitis/genetics , DNA Methylation/genetics , DNA-Binding Proteins/genetics , Dioxygenases , Forkhead Transcription Factors/genetics , Homeostasis/genetics , Homeostasis/immunology , Humans , Interleukin-2/immunology , Mice , Mice, Inbred C57BL , Mice, Knockout , Proto-Oncogene Proteins/genetics , STAT5 Transcription Factor/metabolism , Smad3 Protein/metabolism , T-Lymphocytes, Regulatory/transplantation , Transforming Growth Factor beta/immunologyABSTRACT
Anaerobic ammonium oxidation (anammox) granulation which contributed to system stabilization and performance improvement has great potential in the field of wastewater nitrogen removal. The researchers fractionated anammox granules into small-size (0.5-0.9 mm), medium-size (1.8-2.2 mm), and large-size (2.8-3.5 mm) categories to examine their properties and mechanisms. Various analyses, including high-throughput sequencing, determination of inorganic elements and extracellular polymeric substances (EPS), and microbial function prediction, were conducted to characterize these granules and understand their impact. The results revealed distinct characteristics among the different-sized granules. Medium-size granules exhibited the highest sphericity, EPS content, and anammox abundance. In contrast, large-size granules had the highest specific surface area, heme c content, specific anammox activity, biodiversity, and abundance of filamentous bacteria. Furthermore, the precipitates within the granules were identified as CaCO3 and MgCO3, with the highest inorganic element content found in the large-size granules. Microbial community and function annotation also varied with granule size. Based on systematic analysis, the researchers concluded that cell growth, chemical precipitation, EPS secretion, and interspecies interaction all played a role in granulation. Small-size granules were primarily formed through cell growth and biofilm formation. As granule size increased, EPS secretion and chemical precipitation became more influential in the granulation process. In the large-size granules, chemical precipitation and interspecies interaction, including synergistic effects with nitrifying, denitrifying, and filamentous bacteria, as well as metabolic cross-feeding, played significant roles in aggregation. This interplay ultimately contributed to higher anammox activity in the large-size granules. By fully understanding the mechanisms involved in granulation, this study provides valuable insights for the acclimation of anammox granules with optimal sizes under different operational conditions.
ABSTRACT
Digestive slurry normally contains various nutrient ions with high concentrations, including NH4+, PO43-, K+, Mg2+, Ca2+ and SO42-, which is a resource pool for nutrient recovery. In this study, a synchronously cationic and anionic selective electrodialysis (SCAE) was developed to recover anionic and cationic nutrient ions. Results showed that SCAE could synchronously recover more than 85.0%, 90.2% and 97.8% of PO43-, SO42- and other cations (including NH4+, K+, Ca2+, Mg2+) from the simulated digestive slurry, respectively. The ionic permeation sequence, NH4+ > K+ > Ca2+ > Mg2+ for cations, and SO42- > PO43- for anions, was affected by hydrated radius and hydration numbers, and did not alter despite the variation in electric field. High electrolyte concentration in the product streams would promote the recovery efficiency of both divalent cations and anions due to the ionic replacement effect and the demand for charge neutrality. Under continuous operation, the maximum concentrations of PO43-, SO42-, Mg2+, Ca2+, NH4+ and K+ in product streams reached 231.9, 496.6, 180.7, 604.3, 9,648.4 and 4,571.4 mg·L-1, respectively. By directly mixing different streams, the feasibility of producing mineral fertilizers without dosing externally precipitating chemicals was proved. Struvite, NH4HSO4 and potassium chloride minerals were produced successfully. The outcome provided an optional method for nutrient recovery from wastewater.
Subject(s)
Nutrients , Wastewater , Ions , Struvite , ElectricityABSTRACT
The change in phenols, polysaccharides and volatile profiles of noni juice from laboratory- and factory-scale fermentation was analyzed during a 63-day fermentation process. The phenol and polysaccharide contents and aroma characteristics clearly changed according to fermentation scale and time conditions. The flavonoid content in noni juice gradually increased with fermentation. Seventy-three volatile compounds were identified by solid-phase microextraction coupled with gas chromatography-mass spectrometry (SPME-GC-MS). Methyl hexanoate, 3-methyl-3-buten-1-ol, octanoic acid, hexanoic acid and 2-heptanone were found to be the main aroma components of fresh and fermented noni juice. A decrease in octanoic acid and hexanoic acid contents resulted in the less pungent aroma in noni juice from factory-scale fermentation. The results of principal component analysis of the electronic nose suggested that the difference in nitrogen oxide, alkanes, alcohols, and aromatic and sulfur compounds, contributed to the discrimination of noni juice from different fermentation times and scales.
Subject(s)
Fermentation , Morinda/chemistry , Phenols/analysis , Polysaccharides/analysis , Volatile Organic Compounds/analysis , Electronic Nose , Gas Chromatography-Mass Spectrometry , KineticsABSTRACT
Responses of a microbial community in the completely autotrophic nitrogen removal over nitrite (CANON) process, which was shocked by a pH of 11.0 for 12 h, were investigated. During the recovery phase, the performance, anaerobic ammonia oxidation (anammox) activity, microbial community, and correlation of bacteria as well as the influencing factors were evaluated synchronously. The performance of the CANON process deteriorated rapidly with a nitrogen removal rate (NRR) of 0.13 kg·m-3·d-1, and Firmicutes, spore-forming bacteria, were the dominant phyla after alkaline shock. However, it could self-restore within 107 days after undergoing four stages, at which Planctomycetes became dominant with a relative abundance of 64.62%. Network analysis showed that anammox bacteria (Candidatus Jettenia, Kuenenia, and Brocadia) were positively related to some functional bacteria such as Nitrosomonas, SM1A02, and Calorithrix. Canonical correspondence analysis presented a strong correlation between the microbial community and influencing factors during the recovery phase. With the increase of nitrogen loading rate, the decrease of free nitrous acid and the synergistic effects, heme c content, specific anammox activity (SAA), NRR, and the abundance of dominant genus increased correspondingly. The increase of heme c content regulates the quorum sensing system, promotes the secretion of extracellular polymeric substances, and further improves SAA, NRR, and the relative abundance of the dominant genus. This study highlights some implications for the recovery of the CANON reactor after being exposed to an alkaline shock.
Subject(s)
Antacids/toxicity , Bioreactors , Microbiota/drug effects , Microbiota/physiology , Ammonium Compounds/chemistry , Ammonium Compounds/metabolism , Anaerobiosis , Filtration/instrumentation , Heme/analogs & derivatives , Hydrogen-Ion Concentration , Oxidation-Reduction , Pilot Projects , Signal Transduction , Waste Disposal, Fluid/methods , WastewaterABSTRACT
Anaerobic ammonium oxidation (anammox) pathway is sensitive to organic matter, and its recovery requires reliable evidence regarding the dominance of anammox in N-removal. This study showed that the anammox process deteriorated, with N-removal efficiencies rapidly decreasing from 87.2 to 45.7% when reactors were exposed to COD shocks of 1.12, 2.24 and 3.36 g L-1 (COD/N ratio 2, 4 and 6). Comprehensive assessments of water quality, microbial characteristics and isotope analysis were adopted to investigate anammox recovery. Operational performance took 8-20 days to recover; anammox relative abundance recovered after 20 days, based on the results of fluorescence in situ hybridisation and quantitative PCR; and the anammox pathway contributed to 80.0-91.5% of N-loss 40 days after COD shock terminated, based on the results of the isotope labelling experiment. Therefore, a complete recovery required 40 days. The isotope labelling method supplied a reliable reference for recovery assessment of anammox system in real-world applications.
Subject(s)
Ammonium Compounds/metabolism , Isotope Labeling , Nitrogen/metabolism , Wastewater/microbiology , Water Microbiology , Water Quality , Anaerobiosis , Oxidation-ReductionABSTRACT
Studies have shown that long noncoding RNA Zinc finger E-box-binding homeobox 2 antisense RNA 1 (ZEB2-AS1) is involved in the progression of lung cancer, bladder cancer, and hepatocellular carcinoma. However, its role in the pathogenesis of gastric cancer remains unknown. The Wnt/ß-catenin pathway contributes to the development of gastric cancer. ZEB2-AS1 expression was firstly detected in the gastric carcinoma tissue samples as well as in gastric cancer cells. Knockdown of ZEB2-AS1 was performed by ZEB2-AS1-shRNA, and the viability, migration, invasion, and apoptosis of gastric cancer cells were determined by CCK-8, scratch assay, transwell, and flow cytometry, respectively. Furthermore, levels of Ki-67, PCNA, VEGF, MMP9, epithelial-mesenchymal transition (EMT) markers (E-cadherin, Vimentin and ZEB2), cleaved caspase 3/8/9 and PARP, active ß-catenin, c-Myc, cyclinD1, and AXIN2 were assayed by Western blot or real-time PCR. Additionally, the role and mechanism of ZEB2-AS1 were confirmed in a xenograft nude mouse model. We found ZEB2-AS1 expression was increased in gastric carcinoma samples, and it was correlated with tumor progression. Also, its expression was elevated in gastric cancer cells. Knockdown of ZEB2-AS1 reduced the proliferation, migration, invasion, and EMT, but increased the apoptosis of gastric carcinoma cells. Furthermore, ZEB2-AS1 downregulation remarkably suppressed the expression of Ki-67, PCNA, VEGF and MMP9, and the activation of Wnt/ß-catenin signaling, whereas elevated the levels of cleaved caspase 3/8/9 and PARP in gastric cancer cells. And ZEB2 overexpression reversed the effects of ZEB2-AS1 downregulation on the proliferation, EMT and inactivation of Wnt/ß-catenin signaling. Additionally, ZEB2-AS1 knockdown inhibited tumor growth, Ki-67 staining, and the expression of VEGF, MMP9, active ß-catenin, c-Myc, cyclinD1, and AXIN2 in mice. In conclusion, ZEB2-AS1 promotes the tumorigenesis of gastric carcinoma that is related to the upregulation of ZEB2 and the activation of the Wnt/ß-catenin pathway.
Subject(s)
Down-Regulation , Gene Expression Regulation, Neoplastic , RNA, Long Noncoding/biosynthesis , RNA, Neoplasm/biosynthesis , Stomach Neoplasms/metabolism , Wnt Signaling Pathway , Cell Line, Tumor , Humans , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , RNA, Long Noncoding/genetics , RNA, Neoplasm/genetics , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , beta Catenin/genetics , beta Catenin/metabolismABSTRACT
OBJECTIVES: Temporomandibular joint osteoarthritis (TMJOA) is approximately twice as prevalent in women than in men. Synoviocytes are believed to play a critical role in joint inflammation. However, it is unknown whether synoviocytes from different genders possess sexual dimorphisms that contribute to female-predominant TMJOA. MATERIALS AND METHODS: Freund's complete adjuvant combined with monosodium iodoacetate was used to induce TMJOA in female and male rats. Histologic and radiographic features were used to evaluate TMJOA. The expression of CD68, MCP-1, iNOS, and IL-1ß was detected by immunohistochemistry and real-time PCR. Primary fibroblast-like synoviocytes (FLSs) isolated from the synovial membrane of female and male rats were used for in vitro experiments. RESULTS: Female rats showed aggravated TMJOA features as compared to male rats. Increased expression of iNOS and IL-1ß was detected in synovial membrane from female TMJOA rats as compared to male rats. Furthermore, greater amounts of CD68-positive macrophage infiltration and increased MCP-1 expression around the synovial membrane were detected in female TMJOA rats compared to males. Primary cultured FLSs from female rats showed higher sensitivity to TNF-α treatment and recruited increased macrophage migration than male FLSs. More important, ovariectomy (OVX) by ablation in female rats repressed the sensitivity of female FLSs to TNF-α treatment due to the loss of estrogen production. Blockage of the estrogen receptor repressed estrogen-potentiated TNF-α-induced pro-inflammatory cytokine expression in OVX-FLSs. Moreover, the injection of estrogen receptor antagonists relieved the cartilage destruction and bone deterioration of TMJOA in female rats. CONCLUSION: Estrogen-sensitized synoviocytes in female rats may contribute to gender differences in the incidence and progression of TMJOA.
Subject(s)
Estrogens , Osteoarthritis/metabolism , Synoviocytes/metabolism , Temporomandibular Joint Disorders/metabolism , Animals , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Cell Movement/drug effects , Cells, Cultured , Chemokine CCL2/metabolism , Estrogen Receptor Antagonists/pharmacology , Estrogens/metabolism , Estrogens/pharmacology , Female , Interleukin-1beta/metabolism , Macrophages/metabolism , Macrophages/physiology , Male , Nitric Oxide Synthase Type II/metabolism , Osteoarthritis/pathology , Ovariectomy , Rats , Rats, Sprague-Dawley , Receptors, Estrogen/antagonists & inhibitors , Sex Factors , Synovial Membrane/metabolism , Synoviocytes/drug effects , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
The aim of this work was to evaluate the main nutrients and their antioxidant properties of a Chinese wild edible fruit, Passiflora foetida, collected from the ecoregion of Hainan province, China. The analytical results revealed that P. foetida fruits were rich in amino acids (1097 mg/100 g in total), minerals (595.75 mg/100 g in total), and unsaturated fatty acids (74.18 g/100 g in total fat). The lyophilized powder of edible portion contained the higher polyphenols content than the inedible portion powder. The UPLC-Q-TOF-MSE analysis of the extractable and non-extractable phenolics indicated the presence of 65 compounds including 39 free phenolics, 14 insoluble-glycoside-phenolics, and 22 insoluble-ester-phenolics. In addition, the non-extractable phenolics obtained by alkali hydrolysis showed significant antioxidant activities by/through DPPH and ABTS radical scavenging. These findings of P. foetida fruits, for the first time, suggest that these polyphenol-rich fruits may have potential nutraceutical efficacies.
Subject(s)
Antioxidants/chemistry , Passiflora/chemistry , Plant Extracts/chemistry , Polyphenols/chemistry , China , Flavonoids/chemistry , Fruit/chemistry , Nutrition Assessment , Phenols/chemistryABSTRACT
Longan (Dimcarpus longan Lour.) is a kind of traditional fruit used as a medicine and a food. Fresh longan is primarily consumed as a fruit, whereas dried longan is commonly employed for medicinal purposes. The differences in the immunomodulatory activities and mechanisms of polysaccharides between dried and fresh longan remain unclear. The present study comparatively analyzed the mechanisms of macrophage activation induced by polysaccharides from dried (LPG) and fresh longan (LPX). The results revealed that LPG and LPX differentially promoted macrophage phagocytosis and the secretion of NO, TNF-α, and IL-6. RNA-seq analysis revealed that LPG and LPX differentially affected gene expression in macrophages. The LPG treatment identified Tnf and chemokine-related genes as core genes, while myd88 and interferon-related genes were the core genes affected by LPX. A comprehensive analysis of the differentially expressed genes showed that LPG initiated macrophage activation primarily through the TLR2/4-mediated TRAM/TRAF6 and CLR-mediated Src/Raf1 NF-κB signaling pathways. LPX initiated macrophage activation predominantly via the CLR-mediated Bcl10/MALT1 and NLR-mediated Rip2/TAK1 MAPK and NF-κB signaling pathways. Interestingly, the non-classical NF-κB signaling pathway was activated by polysaccharides in both dried and fresh longan to elicit a slow, mild immune response. LPG tends to promote immune cell migration to engage in the immune response, while LPX facilitates antigen presentation to promote T cell activation. These findings contribute insights into the mechanisms underlying the differences in bioactivity between dried and fresh longan and their potential applications in immune-enhancing strategies and functional-food development.
Subject(s)
Fruit , Macrophage Activation , Macrophages , Phagocytosis , Polysaccharides , Sapindaceae , Signal Transduction , Macrophage Activation/drug effects , Polysaccharides/pharmacology , Animals , Mice , RAW 264.7 Cells , Macrophages/drug effects , Macrophages/metabolism , Macrophages/immunology , Signal Transduction/drug effects , Fruit/chemistry , Sapindaceae/chemistry , Phagocytosis/drug effects , NF-kappa B/metabolismABSTRACT
Antimicrobial blue light (aBL) is utilized as a new approach to inhibit the growth of Staphylococcus aureus (S. aureus). Mediated by the endogenous chromophore, aBL possesses the similar photokilling property with aPDI (antimicrobial photodynamic inactivation), however, their mechanistic discrepancies in triggering the death of staphylococcal cells are not yet understood. Here, we describe the use of a 460-nm-LED to curb the viability of S. aureus. According to the results, the bacterial survival was sharply decreased when blue light was applied, reaching a maximum of 4.11 ± 0.04 log10 units. Moreover, the membrane integrity was damaged by aBL, causing the leakage of intracellular DNA. Transcriptomic analysis indicates the divergent gene expression upon either aBL or aPDI, with pathways such as transport, DNA repair, expression regulation and porphyrin massively affected by aBL. Among the commonly regulated genes, LrgA was underpinned on account of its involvement with biofilm formation and protein transport. By comparing the wildtype with the LrgA-overexpressing (LrgA+) strain, the survival rate, membrane penetration, surface structure and biofilm formation were, to a varying degree, improved for LrgA+, which may suggest that LrgA plays essential roles in modulating the responsiveness of S. aureus. Besides, LrgA may function through regulating the expression of autolysis-related systems. Finally, LrgA overexpression did not attenuate but aggravate the impairment induced by aPDI, showcasing a distinct responsive strategy from aBL. Taken together, this study unveils a unique molecular alteration for the aBL-mediated inactivation, providing the basis of utilizing blue light to reduce the harm brought by S. aureus.
Subject(s)
Bacterial Proteins , Biofilms , Blue Light , Staphylococcus aureus , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Biofilms/drug effects , Biofilms/radiation effects , Gene Expression Regulation, Bacterial/radiation effects , Gene Expression Regulation, Bacterial/drug effects , Microbial Viability/radiation effects , Microbial Viability/drug effects , Porphyrins/chemistry , Porphyrins/pharmacology , Staphylococcus aureus/drug effects , Staphylococcus aureus/radiation effects , Staphylococcus aureus/genetics , Staphylococcus aureus/physiology , Transcription, Genetic/radiation effects , Transcription, Genetic/drug effectsABSTRACT
Dyes contaminating the sewages have seriously threatened the living beings and their separation from wastewater in terms of potential resource recovery is of high value. Herein, both of metal node doping and ligand group grafting were taken into account to enhance the adsorption selectivity of Fe-MOFs towards cationic dyes. The positive correlation between copper doping amount and selective coefficient (∂MOMB) for methylene blue (MB) over methyl orange (MO) within a certain range was mainly attributed to the increased surface negative charges via partial replacement of Fe(III) with Cu(II). Moreover, the amount of surface negative charges was further increased after amino functionalization and there was a synergism between Cu(II) and -NH2 in selectivity enhancement. As a result, Fe0.6Cu0.4-BDC-NH2 exhibited a 22.5-times increase in ∂MOMB and other cationic dyes including malachite green (MG) and rhodamine B (Rh. B) could also be selectively separated from binary and quaternary mixed dye systems. Moreover, Fe0.6Cu0.4-BDC-NH2 showed many superiorities like a wide pH range of 4.0-8.0, strong anti-interference ability over various inorganic ions, good recyclability, and stability. The adsorption kinetics and isotherm suggested that the MB adsorption process was a homogeneous single-layer chemisorption. Additionally, the thermodynamics manifested that the overall process was exothermic and spontaneous. According to the FT-IR and XPS spectra analysis, the electrostatic interaction and hydrogen bonding were determined as the main driving forces, and π-π interaction also contributed to the adsorption process.
ABSTRACT
Activating autologous stem cells after the implantation of biomaterials is an important process to initiate bone regeneration. Although several studies have demonstrated the mechanism of biomaterial-mediated bone regeneration, a comprehensive single-cell level transcriptomic map revealing the influence of biomaterials on regulating the temporal and spatial expression patterns of mesenchymal stem cells (MSCs) is still lacking. Herein, the osteoimmune microenvironment is depicted around the classical collagen/nanohydroxyapatite-based bone repair materials via combining analysis of single-cell RNA sequencing and spatial transcriptomics. A group of functional MSCs with high expression of matrix Gla protein (Mgp) is identified, which may serve as a pioneer subpopulation involved in bone repair. Remarkably, these Mgp high-expressing MSCs (MgphiMSCs) exhibit efficient osteogenic differentiation potential and orchestrate the osteoimmune microenvironment around implanted biomaterials, rewiring the polarization and osteoclastic differentiation of macrophages through the Mdk/Lrp1 ligand-receptor pair. The inhibition of Mdk/Lrp1 activates the pro-inflammatory programs of macrophages and osteoclastogenesis. Meanwhile, multiple immune-cell subsets also exhibit close crosstalk between MgphiMSCs via the secreted phosphoprotein 1 (SPP1) signaling pathway. These cellular profiles and interactions characterized in this study can broaden the understanding of the functional MSC subpopulations at the early stage of biomaterial-mediated bone regeneration and provide the basis for materials-designed strategies that target osteoimmune modulation.
Subject(s)
Bone Regeneration , Calcium-Binding Proteins , Collagen , Durapatite , Matrix Gla Protein , Mesenchymal Stem Cells , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/immunology , Bone Regeneration/genetics , Bone Regeneration/immunology , Animals , Durapatite/metabolism , Calcium-Binding Proteins/genetics , Calcium-Binding Proteins/metabolism , Mice , Collagen/metabolism , Collagen/genetics , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , Osteogenesis/drug effects , Osteogenesis/genetics , Osteogenesis/immunology , Cell Differentiation/genetics , Biocompatible MaterialsABSTRACT
BACKGROUND: The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years, which also may lead to some complications such as alveolar bone resorption or tooth root resorption. Low-intensity pulsed ultrasound (LIPUS), a noninvasive physical therapy, has been shown to promote bone fracture healing. It is also reported that LIPUS could reduce the duration of orthodontic treatment; however, how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear. AIM: To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement (OTM) model and explore the underlying mechanisms. METHODS: A rat model of OTM was established, and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections. In vitro, human bone marrow mesenchymal stem cells (hBMSCs) were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction, Western blot, alkaline phosphatase (ALP) staining, and Alizarin red staining. The expression of Yes-associated protein (YAP1), the actin cytoskeleton, and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA (siRNA) application via immunofluorescence. RESULTS: The force treatment inhibited the osteogenic differentiation potential of hBMSCs; moreover, the expression of osteogenesis markers, such as type 1 collagen (COL1), runt-related transcription factor 2, ALP, and osteocalcin (OCN), decreased. LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force. Mechanically, the expression of LaminA/C, F-actin, and YAP1 was downregulated after force treatment, which could be rescued by LIPUS. Moreover, the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment. Consistently, LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo. The decreased expression of COL1, OCN, and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS. CONCLUSION: LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis, which may be a promising strategy to reduce the orthodontic treatment process.
ABSTRACT
Streptococcus pneumoniae is a Gram-positive, extracellular bacterium that is responsible for significant mortality and morbidity worldwide. Pneumolysin (PLY), a cytolysin produced by all clinical isolates of the pneumococcus, is one of the most important virulence factors of this pathogen. We have previously reported that PLY is an essential factor for activation of caspase-1 and consequent secretion of IL-1ß and IL-18 in macrophages infected with S. pneumoniae. However, the host molecular factors involved in caspase-1 activation are still unclear. To further elucidate the mechanism of caspase-1 activation in macrophages infected with S. pneumoniae, we examined the involvement of inflammasomes in inducing this cellular response. Our study revealed that apoptosis-associated specklike protein containing a caspase recruitment domain (ASC), an adaptor protein for inflammasome receptors such as nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2), is essentially required for the induction of caspase-1 activation by S. pneumoniae. Caspase-1 activation was partially impaired in NLRP3(-/-) macrophages, whereas knockdown and knockout of AIM2 resulted in a clear decrease in caspase-1 activation in response to S. pneumoniae. These results suggest that ASC inflammasomes, including AIM2 and NLRP3, are critical for caspase-1 activation induced by S. pneumoniae. Furthermore, ASC(-/-) mice were more susceptible than wild-type mice to S. pneumoniae, with impaired secretion of IL-1ß and IL-18 into the bronchoalveolar lavage after intranasal infection, suggesting that ASC inflammasomes contribute to the protection of host from infection with PLY-producing S. pneumoniae.
Subject(s)
Caspase 1/metabolism , Cytoskeletal Proteins/physiology , Immunity, Innate , Inflammasomes/physiology , Pneumococcal Infections/immunology , Pneumococcal Infections/metabolism , Animals , Apoptosis Regulatory Proteins , Bacterial Proteins/antagonists & inhibitors , Bacterial Proteins/biosynthesis , CARD Signaling Adaptor Proteins , Carrier Proteins/physiology , Caspase 1/deficiency , Caspase 1/genetics , Cell Line , Cell Line, Transformed , Cells, Cultured , Cytoskeletal Proteins/deficiency , Cytoskeletal Proteins/genetics , DNA-Binding Proteins , Disease Resistance/immunology , Enzyme Activation/immunology , Female , Interleukin-18/metabolism , Interleukin-1beta/metabolism , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Knockout , NLR Family, Pyrin Domain-Containing 3 Protein , Nuclear Proteins/physiology , Pneumococcal Infections/enzymology , Streptolysins/antagonists & inhibitors , Streptolysins/biosynthesisABSTRACT
Rice bean (Vigna umbellata) is a medicinal and dietary legume rich in polyphenols. In this study, the free and bound phenolics in rice bean were extracted by water, 80% methanol, and acid, base, and composite enzymatic hydrolysis, respectively. The polyphenol profiles of the extracted fractions were analyzed. The outcome demonstrated that base hydrolysis was the most effective way to liberate bound phenolics from rice bean (14.18 mg GAE/g DW), which was 16.68 and 56.72 folds higher than those extracted by acid and enzymatic hydrolysis, respectively. The bound polyphenols released by base hydrolysis contributed to 71.15% of the total phenolic content. A total of 35 individual phenolics was identified, of which isoquercitrin, procyanidin B1, rutin, taxifolin, and catechin were the main monomeric phenolics in the free fraction, while gallic acid, protocatechuic acid, p-hydroxybenzoic acid, catechin, and phloroglucinol were the main monomeric phenolics in the bound fraction. In comparison to the free phenolics extracted by water and 80% methanol and the bound phenolics extracted using acid and composite enzymatic hydrolysis, the bound phenolics from base hydrolysis had a superior antioxidant capacity. The antioxidant activity of rice bean is primarily attributed to individual phenolics such as catechin, abundant both in free and bound fractions, and also p-hydroxybenzoic acid, gallic acid, and protocatechuic acid in bound fractions. The bound phenolics of rice bean were first reported and showed large differences with the composition of free phenolics. This work suggests that the bound fraction of rice bean must be taken into account in assessing its potential benefits to health.
ABSTRACT
Electrochemical advanced oxidation process (EAOP) is recommended for high-strength refractory organics wastewater treatment, but the accompanying chlorinated byproduct generation becomes a bottleneck that limits the application of this technology to actual wastewater. In this study, we applied EAOP (0.4-40 mA cm-2) to treat ultrafiltration effluent of an actual landfill leachate, and quantitatively assessed the toxicities of the dominant chlorinated byproducts in EAOP-treated effluent. Considering both toxic effect and dose, it followed the order: active chlorine > chlorate > perchlorate > organochlorines. The toxic active chlorine could spontaneously decompose by settling. And secondary bioreactor originally serving for denitrification could be used to reduce perchlorate and chlorate. The effects of residual active chlorine and extra carbon addition on simultaneous denitrification, perchlorate, and chlorate reduction were investigated. It seemed that 20 mg of active chlorine was an acceptable level to bioactivity, and sufficient electron donors favored the removal of chlorate and perchlorate. Pseudomonas was identified as an active chlorine tolerant chlorate-reducing bacteria. And Thauera was responsible for perchlorate reduction under the conditions of sufficient carbon source supply. Our results confirmed that the perchlorate and chlorate concentrations in the effluent below their health advisory levels were achievable, solving the issue of toxic chlorinated byproduct generation during EAOP. This study provided a solution to realistic application of EAOP to treat high chloride wastewater.
Subject(s)
Wastewater , Water Pollutants, Chemical , Chlorine , Chlorides , Perchlorates , Chlorates , Oxidation-Reduction , CarbonABSTRACT
Ellagic acid (EA) exhibits potential antiaging activity. Differences in individual ability to produce urolithins may result in large interindividual variability in the health effects of EA. Therefore, the effects and mechanism of EA on d-galactose-induced aging, considering urolithin A-producing ability, were investigated. Our results showed that EA improved cognitive impairment and hippocampal damage, increased the GABA (by 107.84-117.86%) and 5-HT (by 72.56-100.85%) levels, and suppressed the inflammatory and oxidative stress in aging rats. Thirteen plasma metabolites and 12 brain metabolites were improved by EA administration in aging rats. In particular, EA showed a better anti-aging effect in high-UroA-producing rats than in the low counterparts, while antibiotic intervention almost offset EA-alleviated aging induced by d-gal. Furthermore, the lower ratio of Firmicutes and Bacteroidota as well as the greater abundances of Akkermansia (by 139.21%), Bifidobacterium (by 88.04%), Clostridium_sensu_stricto_1 (by 183.47%), Lactobacillus (by 97.23%), and Turicibacter (by 83.06%) were observed in the high-UroA-producing group compared with the model group (p < 0.05). These findings provide novel insights into the anti-aging effects of EA and suggest that the ability of the gut microbiota responding to EA largely determines EA's anti-aging performance.
Subject(s)
Gastrointestinal Microbiome , Rats , Animals , Ellagic Acid/metabolism , Aging , Coumarins/pharmacologyABSTRACT
Annexin A3 (ANXA3), a member of Annexin family, is reported to mediate membrane transport and cancer development. However, the effect of ANXA3 on osteoclast formation and bone metabolism is still unclear. In this study, we found that knockdown of ANXA3 can significantly inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation through NF-κB signaling. ANXA3 downregulation abrogated the expression of osteoclast-specific genes, including Acp5, Mmp9 and Ctsk in osteoclast precursors. Moreover, lentiviral of shRNA against ANXA3 reversed the bone loss in osteoporosis using ovariectomized mice model. Mechanistically, we found that ANXA3 directly bound to RANK and TRAF6 to accelerate osteoclast differentiation by promoting their transcription and limiting degradation. In conclusion, we propose a fundamentally novel RANK-ANXA3-TRAF6 complex to effectively modulate the formation and differentiation of osteoclast to manipulate bone metabolism. The ANXA3-targeted therapeutic strategy may provide new insight for bone degrading-related diseases prevention and treatment.
Subject(s)
Bone Resorption , Osteoclasts , Mice , Animals , Osteoclasts/metabolism , TNF Receptor-Associated Factor 6/metabolism , Annexin A3/metabolism , Annexin A3/pharmacology , Bone and Bones/metabolism , Signal Transduction , NF-kappa B/metabolism , RANK Ligand/metabolism , Cell Differentiation , Bone Resorption/metabolism , OsteogenesisABSTRACT
An active polysaccharide (LP) from longan was purified and characterized. LP consisted of galactose and glucose in a molar ratio of 1.5: 98.5, with a molecular weight of 4.67 × 107 g/mol. The main backbone of LP was T-α-D-Glcp-[(1 â 6)-α-D-Glcp-(1 â 6)-α-D-Glcp]n. After simulated gastrointestinal digestion, the molecular weight distribution, monosaccharide composition, and major glycosidic bonds of LP were not significantly changed. LP and digested LP (DLP) reduced phagocytosis and promoted IL-10 and IL-12 secretion of dendritic cells. In addition, the effects of LP and DLP on activating dendritic cells showed no significant difference. This study helps to illuminate the potential mode of immunomodulatory action of longan polysaccharides in vivo.