Rheumatoid arthritis (RA) is one of the chronic systemic autoimmune diseases that cardinally affect the joints. Many people all over the world suffer from the disease. Fibroblast‐like synoviocytes ...(FLSs) play a significant role in the occurrence and development of RA. The long noncoding RNA maternally expressed gene 3 (MEG3) is an imprinted gene, which participates in various cancers as a tumor suppressor. Previous studies have shown that nucleotide oligomerization domain (NOD)‐like receptors 5 (NLRC5) plays a key role in inflammatory and autoimmune diseases. Nonetheless, we know very little about the biofunctionality of MEG3 during the development of RA. In this paper, we used complete Freund's adjuvant (CFA)‐induced rats as RA animal models. The level of MEG3 significantly reduced in CFA‐induced synovial tissues and FLSs, whereas the NLRC5 levels were increased. Enforced expression of MEG3 may be responsible for the decreased level of NLRC5 and inflammatory cytokine level. The results of methylation‐specific PCR suggested that the MEG3 gene promoter was significantly methylated in CFA‐induced synovial tissues and FLSs. More important, hypermethylation of MEG3 promoter could be inhibited by 5‐aza‐2‐deoxycytidine (5‐azadC; methylation inhibitor). Besides, the expression of NLRC5 significantly decreased followed by 5‐azadc. Furthermore, DNA methyltransferases 1 (DNMT1) increased in CFA‐induced synovial tissues and cells. These results indicated that MEG3 regulates RA by targeting NLRC5 potentially.
Maternally expressed gene 3 (MEG3) may be involved in the development of rheumatoid arthritis (RA) by affecting the proliferation of fibroblast‐like synoviocytes (FLSs), whereas nucleotide oligomerization domain (NOD)‐like receptors 5 (NLRC5) promotes proliferation of FLSs in RA. Enforced expression of MEG3 decreased NLRC5 expression. These results further verified that MEG3 regulates RA by targeting NLRC5 potentially.
Gout arthritis (GA) is a common and curable type of inflammatory arthritis that has been attributed to a combination of genetic, environmental and metabolic factors. Chronic deposition of monosodium ...urate (MSU) crystals in articular and periarticular spaces as well as subsequent activation of innate immune system in the condition of persistent hyperuricemia are the core mechanisms of GA. As is well known, drugs for GA therapy primarily consists of rapidly acting anti-inflammatory agents and life-long uric acid lowering agents, and their therapeutic outcomes are far from satisfactory. Although MSU crystals in articular cartilage detected by arthrosonography or in synovial fluid found by polarization microscopy are conclusive proofs for GA, the exact molecular mechanism of NLRP3 inflammasome activation in the course of GA still remains mysterious, severely restricting the early diagnosis and therapy of GA. On the one hand, the activation of Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome requires nuclear factor kappa B (NF-κB)-dependent transcriptional enhancement of NLRP3, precursor (pro)-caspase-1 and pro-IL-1β, as well as the assembly of NLRP3 inflammasome complex and sustained release of inflammatory mediators and cytokines such as IL-1β, IL-18 and caspase-1. On the other hand, NLRP3 inflammasome activated by MSU crystals is particularly relevant to the initiation and progression of GA, and thus may represent a prospective diagnostic biomarker and therapeutic target. As a result, pharmacological inhibition of the assembly and activation of NLRP3 inflammasome may also be a promising avenue for GA therapy. Herein, we first introduced the functional role of NLRP3 inflammasome activation and relevant biological mechanisms in GA based on currently available evidence. Then, we systematically reviewed therapeutic strategies for targeting NLRP3 by potentially effective agents such as natural products, novel compounds and noncoding RNAs (ncRNAs) in the treatment of MSU-induced GA mouse models. In conclusion, our present review may have significant implications for the pathogenesis, diagnosis and therapy of GA.
Background
Dysregulated bile acid (BA) metabolism has been linked to steatosis, inflammation, and fibrosis in nonalcoholic fatty liver disease (NAFLD).
Aim
To determine whether circulating BA levels ...accurately stage liver fibrosis in NAFLD.
Methods
We recruited 550 Chinese adults with biopsy‐proven NAFLD and varying levels of fibrosis. Ultra‐performance liquid chromatography coupled with tandem mass spectrometry was performed to quantify 38 serum BAs.
Results
Compared to those without fibrosis, patients with mild fibrosis (stage F1) had significantly higher levels of secondary BAs, and increased diastolic blood pressure (DBP), alanine aminotransferase (ALT), body mass index, and waist circumstance (WC). The combination of serum BAs with WC, DBP, ALT, or Homeostatic Model Assessment for Insulin Resistance performed well in identifying mild fibrosis, in men and women, and in those with/without obesity, with AUROCs 0.80, 0.88, 0.75 and 0.78 in the training set (n = 385), and 0.69, 0.80, 0.61 and 0.69 in the testing set (n = 165), respectively. In comparison, the combination of BAs and clinical/biochemical biomarkers performed less well in identifying significant fibrosis (F2‐4). In women and in non‐obese subjects, AUROCs were 0.75 and 0.71 in the training set, 0.65 and 0.66 in the validation set, respectively. However, these AUROCs were higher than those observed for the fibrosis‐4 index, NAFLD fibrosis score, and Hepamet fibrosis score.
Conclusions
Secondary BA levels were significantly increased in NAFLD, especially in those with mild fibrosis. The combination of serum BAs and clinical/biochemical biomarkers for identifying mild fibrosis merits further assessment.
Secondary bile acids were significantly increased in NAFLD, especially in those with mild fibrosis. The combination of serum bile acids and clinical/biochemical biomarkers for identifying mild fibrosis is worthy of further assessment.
According to the types of organic polymers, the design, preparation, performance and application value of composite membranes using MOFs as fillers were classified and summarized. The future ...development trends and priorities are also discussed and prospected.
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•Proton exchange membranes based on MOFs were reviewed.•PEMs are classified in the light of the types of polymeric matrix.•Proton conduction and conductve mechanism were concluded.•The future development trend of such PEMs was highlighted.
To overcome the defects of traditional proton exchange membranes (PEMs) (Nafion and Nafion-based membranes, etc.), the introduction of proton-conducting MOFs with performance advantages into the PEM system is a smart strategy, many exciting research results have emerged one after another in recent years. For the convenience of researchers and to explore trends for future development, in this review. MOF-based PEMs are divided into the mixed-matrix membranes using MOFs as fillers and PEMs formed by MOFs directly based on different film-forming methods, and the properties of these PEMs are concluded. The following aspects were focused on the preparation strategies and techniques, stability (covering thermal-, water-, chemical-, and mechanical stabilities, etc.), proton conductive properties under damp or anhydrous conditions, and proton conduction mechanism, and structure–activity relationship. Finally, the prospects and challenges of future research are highlighted.
This study aims to explore the mechanism of Liujunzi Decoction in the treatment of 4-nitroquinoline-N-oxide(4NQO)-induced esophageal cancer in mice. One hundred mice of 35-45 days were randomized ...into blank, model, and low-, medium-, and high-concentration(18.2, 36.4, and 54.6 g·kg~(-1), respectively) Liujunzi Decoction groups. The mice in other groups except the blank group had free access to the water containing 100 μg·mL~(-1) 4NQO for 16 weeks for the modeling of esophageal cancer. The mice in the Liujunzi Decoction groups were fed with the diets supplemented with corresponding concentrations of Liujunzi Decoction. The body weight and organ weights were weighed for the calculation of organ indexes. The pathological changes of the esophageal tissue were observed by hematoxylin-eosin(HE) staining. Ultra performance liquid chromatography-mass spectrometry(UPLC-MS/MS) was employed to collect metabolites from mouse serum samples, screen out potential biomarkers, and predict related metabolic pathways. Compared
Innate immunity activates the corresponding immune response relying on multiple pattern recognition receptors (PRRs) that includes pattern recognition receptors (PRRs), like NOD-like receptors ...(NLRs), RIG-I-like receptors (RLRs), and C-type lectin receptors (CLRs), which could accurately recognize invasive pathogens. In particular, NLRs belong to a large protein family of pattern recognition receptors in the cytoplasm, where they are highly correlated with activation of inflammatory response system followed by rapid clearance of invasive pathogens. Among the NLRs family, NLRC5, also known as NOD4 or NOD27, accounts for a large proportion and involves in immune responses far and wide. Notably, in the above response case of inflammation, the expression of NLRC5 remarkably increased in immune cells and immune-related tissues. However, the evidence for higher expression of NLRC5 in immune disease still remains controversial. It is noted that the growing evidence further accounts for the participation of NLRC5 in the innate immune response and inflammatory diseases. Moreover, NLRC5 has also been confirmed to exert a critical role in the control of regulatory diverse signaling pathways. Together with its broad participation in the occurrence and development of immune diseases, NLRC5 can be consequently treated as a potential therapeutic target. Nevertheless, the paucity of absolute understanding of intrinsic characteristics and underlying mechanisms of NLRC5 still make it hard to develop targeting drugs. Therefore, current summary about NLRC5 information is indispensable. Herein, current knowledge of NLRC5 is summarized, and research advances in terms of NLRC5 in characteristics, biological function, and regulatory mechanisms are reviewed.
Under the rapid urbanization, quantitatively assessing the impacts of land use and cover change (LUCC) on ecosystem service is of great significance for regional ecological environment construction. ...Based on the land use maps of Shangqiu City (as the typical agricultural area of North China Plain) in the year of 1990, 2005 and 2015, the spatio-temporal dynamics of land use and ecosystem service were analyzed, and the impacts of LUCC on ecosystem services was quantified with the impact assessment model. The results showed that, from 1990 to 2015, farmland and construction land area, which covered more than 95% of the total area of the research area, changed the most in quantity as -104.38 and 201.59 km
respectively, while forestland, grassland and water area changed the most by 79.3%, -73.7% and -24.2%, respectively. The total value of ecosystem service continuously decreased by 1.005 billion yuan, among which the value of hydrolo-gical regulation service suffered the most. The value of ecosystem service (ESV)
Macroporous cryogels were prepared and used to deplete abundant proteins. It was accomplished based on the sample heterogeneity rather than any exogenous assistance. Human serum was added in monomer ...solutions to synthesize molecularly imprinted polymers; therein some abundant proteins were imprinted in the polyacrylamide cryogels. Meanwhile the rare components remained aqueous. Chromatography and electrophoresis showed that albumin, serotransferrin, and most globulins were depleted by columns packed with the molecularly imprinted polymers. After the depletion, lower abundance proteins were revealed by SDS‐PAGE, peptide fingerprint analysis, and identified by MALDI‐TOF‐MS. This is an example that a “per se imprint” protocol enables to gradually dimidiate proteomes, simplify sample complexities, and facilitate further proteome profiling or biomarker discovery.
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•Proton conductive MOFs based on main-group metals were reviewed.•MOFs are classified in the light of the types of metals.•Proton conduction and conductve mechanism were ...discussed.•The future development trend of such MOFs was highlighted.
Attracted by the excellent structural stability and structural diversity of the metal–organic frameworks based on main group metals, we review the proton conductive properties of such MOFs herein, and hope to provide comprehensive and accurate guidance for related research. The properties of these MOFs are classified and reviewed according to the types of main group metal elements (s-block and p-block). We mainly focus on the following aspects: preparation strategy and synthesis techniques, influence of organic ligands on the final structures, structural stability including thermal, water and chemical stability, the proton conductivity under humidity or anhydrous conditions, the proton conducting mechanisms, and the structure–property relationship. In the end, the highlights and deficiencies of the previous research and the future challenges and trend of the research will be highlighted.
In this work, biogas residues, the remnant of the anaerobic digestion, was used for composting with livestock manure as the co-substrate. It is important for improving the soil quality in China, ...because the negative influence of biogas residues being utilized directly as organic fertilizer (a mainstream way of disposing biogas residues in China) on the soil could be eliminated or mitigated via composting. The composition of composting substrate has a great influence on the composting process. To explore the influence of the composition of the initial mixtures on the physicochemical properties and spectroscopic characteristics of composts, fifteen co-composting of biogas residue, pig manure and chicken manure, with different material ratios, were carried out. Physicochemical and biological indicators were determined. Meanwhile, spectroscopic methods, such as UV-Vis, synchronous fluorescence and 3D-EEM spectra were used for identifying characteristic spectral parameters companied with FRI and PARAFAC. Therefore
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