Protein-protein interactions regulating α-synuclein pathology.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the formation of Lewy bodies (LBs). The main proteinaceous component of LBs is aggregated α-synuclein (α-syn). However, the mechanisms underlying α-syn aggregation are not yet fully understood. Converging lines of evidence indicate that, under certain pathological conditions, various proteins can interact with α-syn and regulate its aggregation. Understanding these protein-protein interactions is crucial for unraveling the molecular mechanisms contributing to PD pathogenesis. In this review we provide an overview of the current knowledge on protein-protein interactions that regulate α-syn aggregation. Additionally, we briefly summarize the methods used to investigate the influence of protein-protein interactions on α-syn aggregation and propagation.

A new comprehensive quantitative index for the assessment of essential amino acid quality in beef using Vis-NIR hyperspectral imaging combined with LSTM.

The quality of beef is usually predicted by measuring a single index rather than a comprehensive index. To precisely determine the essential amino acid (EAA) contents in 360 beef samples, the feasibility of optimized spectral detection techniques based on the comprehensive EAA index (CEI) and comprehensive weight index (CWI) constructed by factor analysis was explored. Two-dimensional correlation spectroscopy (2D-COS) was used to analyse the mechanisms of spectral peak shifts in complex disturbance systems with CEI and CWI contents, and 15 sensitive feature variables were extracted to establish a quantitative analysis model of a long short-term memory network (LSTM). The results indicated that 2D-COS had good predictive performance in both CEI-LSTM (R2P of 0.9095 and RPD of 2.76) and CWI-LSTM (R2P of 0.8449 and RPD of 2.45), which reduced data information by 88%. This indicates that utilizing 2D-COS can eliminate collinearity and redundant information among variables while achieving data dimensionality reduction and simplification of calibration models. Furthermore, a spatial distribution map of the comprehensive EAA content was generated by combining the optimal prediction model. This study demonstrated that the comprehensive index method furnishes a new approach to rapidly evaluate EAA content.

Structural Characterization and Effects on Insulin Resistance of a Novel Chondroitin Sulfate from Halaelurus burgeri Skin.

Several studies have isolated chondroitin sulphate (CHS) from sharks' jaws or cartilage. However, there has been little research on CHS from shark skin. In the present study, we extracted a novel CHS from Halaelurus burgeri skin, which has a novel chemical structure and bioactivity on improvement in insulin resistance. Results using Fourier transform-infrared spectroscopy (FT-IR), 1H-nuclear magnetic resonance spectroscopy (1H-NMR), and methylation analysis showed that the structure of the CHS was [4)-ß-D-GlcpA-(1→3)-ß-D-GlcpNAc-(1→]n with 17.40% of sulfate group concentration. Its molecular weight was 238.35 kDa, and the yield was 17.81%. Experiments on animals showed that this CHS could dramatically decrease body weight, reduce blood glucose and insulin levels, lower lipid concentrations both in the serum and the liver, improve glucose tolerance and insulin sensitivity, and regulate serum-inflammatory factors. These results demonstrated that the CHS from H. burgeri skin has a positive effect in reducing insulin resistance because of its novel structure, which provides a significant implication for the polysaccharide as a functional food.

Anti-Obesity and Gut Microbiota Regulation Effects of Phospholipids from the Eggs of Crab, Portunus Trituberculatus, in High Fat Diet-Fed Mice.

There are resourceful phospholipids in the eggs of the crab, Portunus trituberculatus (Pt-PL). However, their components and bioactivities regarding obesity were unclear. Here, we investigated the composition of Pt-PL and their fatty acids. Moreover, its effects on obesity and gut microbiota were also evaluated in high fat diet (HFD)-fed mice. The results showed that Pt-PL contained 12 kinds of phospholipids, mainly including phosphatidylcholine (PC, 32.28%), phosphatidylserine (PS, 26.51%), phosphatidic acid (PA, 19.61%), phosphatidylethanolamine (PE, 8.81%), and phosphatidylinositol (PI, 7.96%). Polyunsaturated fatty acids (PUFAs) predominated in the fatty acids components of Pt-PL, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Animal experiments demonstrated that Pt-PL significantly alleviated body weight gain, adipose gain, hepatic gain, fasting blood glucose, serum insulin, lipid levels in serum and the liver, and systematic inflammation in HFD-fed mice. Furthermore, Pt-PL regulated gut microbiota, especially in a dramatic reduction in the ratio of Firmicutes to Bacteroidetes at phylum level, as well as significant amelioration in their subordinate categories. Pt-PL reduced fecal lipopolysaccharide and total bile acids, and elevated fecal short chain fatty acid (SCFA) concentrations, particularly acetate and butyrate. These findings suggest that Pt-PL possesses anti-obesity effects and can alter gut microbiota owing to the abundance of PUFAs. Therefore, Pt-PL may be developed as an effective food supplement for anti-obesity and regulation of human gut health.

The role of Sirt6 in osteoarthritis and its effect on macrophage polarization.

Osteoarthritis (OA), the commonest arthritis type, features irreversible cartilage loss and synovitis. It was reported that macrophages have an important function in synovial inflammation, and our team revealed that the amounts of Sirt6, a nicotinamide adenine dinucleotide (NAD)+-dependent histone deacetylase, decrease during synovial inflammation and osteoarthritis. This work aimed to examine the anti-inflammatory properties of Sirt6 in synovial inflammation. Firstly, we compared Sirt6 amounts in acute meniscus injury and OA human knee synovial tissue samples by immunofluorescence and immunoblot. Secondly, Sirt6's suppressive effects on inflammatory markers and macrophage polarization were evaluated. Finally, OA mice were histologically evaluated, and serum inflammatory factors were detected for assessing the impact of Sirt6 overexpression on the mouse synovium. We found significantly lower interleukin-4 (IL-4) amounts and M2 polarization in OA patients compared with control individuals. The expression of Sirt6 was lower in RAW264.7 cells of the lipopolysaccharides (LPS) + interferon-gamma (IFN-γ) group compared with the phosphate buffer saline (PBS) group, but higher than in the IL-4 group. The polarization of macrophages affected Sirt6 expression, which was reduced and elevated in M1 and M2 macrophages, respectively. Sirt6 inhibition could promote the release of proinflammatory cytokines by macrophages in the synovial membrane, induce M1 polarization in macrophages and inhibit M2 polarization in vitro, and Sirt6 overexpression alleviated osteoarthritis in vivo. These data strongly suggested that Sirt6 could inhibit synovial inflammation. Thus, this study provides a novel therapeutic target in osteoarthritis.

Coniferaldehyde prevents articular cartilage destruction in a murine model via Nrf2/HO­1 pathway.

Osteoarthritis (OA) is the most prevalent joint disorder characterized by progressive cartilage damage, resulting in gradual disability among the elderly. We previously provided in vivo evidence that nuclear factor erythroid 2­related factor 2 (Nrf2) deficiency is associated with the development of OA. It has been reported that coniferaldehyde (CFA) acts as a potential Nrf2 activator. The aim of the present study was to investigate the protective effects of CFA against osteoarthritis. A murine model of surgical­induced OA was used in the present study and CFA was administered by peritoneal injection every day, and the knee joints were assessed by histological analysis. The results demonstrated that CFA activated the Nrf2 signaling pathway in primary chondrocytes and articular cartilage from the knee joints. Cartilage damage in mice subjected to the destabilization of the medial meniscus was evidently alleviated by CFA treatment. CFA also robustly suppressed apoptosis induced by H2O2 in murine chondrocytes and reduced the expression of matrix metalloproteinase (MMP)1, MMP3, interleukin (IL)­1 and IL­6 in vivo. On the whole, the findings suggested that CFA exerts a therapeutic effect against OA, and the activation of the Nrf2/heme oxygenase­1 pathway may play a crucial role in CFA­mediated cartilage protection.

Ergosterol limits osteoarthritis development and progression through activation of Nrf2 signaling.

Osteoarthritis (OA) is a common joint disorder characterized by progressive articular cartilage degeneration and destruction and results in gradual disability among middle-aged and elderly patients. Our previous study demonstrated that depletion of nuclear factor erythroid 2-related factor 2 (Nrf2) exacerbated cartilage erosion in an OA model and that activation of the Nrf2 pathway could counter this process. As a downstream target of Nrf2, heme oxygenase (HO) degrades heme to free iron, biliverdin and carbon monoxide (CO), which protects against oxidative stress. Ergosterol (ER), which is extracted from fungi, is a newly discovered Nrf2 activator and displayed efficacy against myocardial injury. The present study aimed to investigate the potential protective effects of ER against cartilage damage during OA. Primary mouse chondrocytes were treated with ER for in vitro assays. Furthermore, mice that underwent destabilization of the medial meniscus surgery were orally administered with ER. Western blotting suggested that ER increased protein expression of Nrf2 and HO-1 in primary chondrocytes and articular cartilage from knee joints. Cartilage damage in knee joints was significantly reduced by ER treatment. Western blotting and PCR analysis confirmed that ER could also suppress the expression of MMP-9 and MMP-13 in vivo and in vitro. The present findings suggested that ER effectively alleviated cartilage degradation and that activation of the Nrf2-heme oxygenase 1 pathway may play a role in ER-mediated cartilage protection against OA.

Low Molecular Weight, 4-O-Sulfation, and Sulfation at Meta-Fucose Positively Promote the Activities of Sea Cucumber Fucoidans on Improving Insulin Resistance in HFD-Fed Mice.

Fucoidans from sea cucumber (SC-FUC) have been proven to alleviate insulin resistance in several species. However, there are few studies that clarify the relationship between their structure and bioactivity. The present study evaluated the influence of molecular weight (Mw), sulfation concentrations (Cs), and sulfation position on improving insulin resistance using SC-FUC. Results showed that fucoidans with lower Mw exerted stronger effects. Having a similar Mw, Acaudina molpadioides fucoidans (Am-FUC) with lower Cs and Holothuria tubulosa fucoidans with higher Cs showed similar activities. However, Isostichopus badionotus fucoidans (higher Cs) activity was superior to that of low-Mw Thelenota ananas fucoidans (Ta-LFUC, lower Cs). Eliminating the effects of Mw and Cs, the bioactivity of Am-FUC with sulfation at meta-fucose exceeded that of Ta-FUC with sulfation at ortho-position. Moreover, the effects of Pearsonothuria graeffei fucoidans with 4-O-sulfation were superior to those of Am-LFUC with 2-O-sulfation. These data indicate that low Mw, 4-O-sulfation, and sulfation at meta-fucose contributed considerably to insulin resistance alleviation by SC-FUC, which could accelerate the development of SC-FUC as a potential food supplement to alleviate insulin resistance.

7,8-Dihydroxyflavone activates Nrf2/HO-1 signaling pathways and protects against osteoarthritis.

The aim of the present study was to investigate the effect of 7,8-dihydroxyflavone (7,8-DHF) against osteoarthritis (OA) and examine its regulatory role in the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway in chondrocytes. Primary mouse chondrocytes were treated with 7,8-DHF to examine the expression of Nrf2 and downstream heme oxygenase 1 (HO-1). The surgical destabilization of the medial meniscus model was used to assess the effectiveness of 7,8-DHF in protecting the cartilage from damage, with knee cartilage harvested from mice for histological analysis. The results revealed that 7,8-DHF activated the Nrf2 signaling pathway in primary chondrocytes. Cartilage degradation in the 7,8-DHF-treated group was reduced significantly compared with that in the vehicle-treated group, according to histological evaluation. The gene expression of matrix metalloproteinase (MMP)1, MMP3, MMP13, interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α were reduced in the cartilage of OA mice following 7,8-DHF treatment. Genetic and protein analyses indicated that the expression levels of HO-1 were upregulated in the cartilage of the knee with OA, and 7,8-DHF treatment further promoted the induction of HO-1. These results suggest that 7,8-DHF may serve as a potential therapeutic agent in OA.

Synthesis, structure and characterization of two copper(II) supramolecular coordination polymers based on a multifunctional ligand 2-amino-4-sulfobenzoic acid.

Copper(II) coordination polymers have attracted considerable interest due to their catalytic, adsorption, luminescence and magnetic properties. The reactions of copper(II) with 2-amino-4-sulfobenzoic acid (H(2)asba) in the presence/absence of the auxiliary chelating ligand 1,10-phenanthroline (phen) under ambient conditions yielded two supramolecular coordination polymers, namely (3-amino-4-carboxybenzene-1-sulfonato-κO(1))bis(1,10-phenanthroline-κ(2)N,N')copper(II) 3-amino-4-carboxybenzene-1-sulfonate monohydrate, [Cu(C7H6N2O5S)(C12H8N2)2](C7H6N2O5S)·H2O, (1), and catena-poly[[diaquacopper(II)]-µ-3-amino-4-carboxylatobenzene-1-sulfonato-κ(2)O(4):O(4')], [Cu(C7H6N2O5S)(H2O)2]n, (2). The products were characterized by FT-IR spectroscopy, thermogravimetric analysis (TGA), solid-state UV-Vis spectroscopy and single-crystal X-ray diffraction analysis, as well as by variable-temperature powder X-ray diffraction analysis (VT-PXRD). Intermolecular π-π stacking interactions in (1) link the mononuclear copper(II) cation units into a supramolecular polymeric chain, which is further extended into a supramolecular double chain through interchain hydrogen bonds. Supramolecular double chains are then extended into a two-dimensional supramolecular double layer through hydrogen bonds between the lattice Hasba(-) anions, H2O molecules and double chains. Left- and right-handed 21 helices formed by the Hasba(-) anions are arranged alternately within the two-dimensional supramolecular double layers. Complex (2) exhibits a polymeric chain which is further extended into a three-dimensional supramolecular network through interchain hydrogen bonds. Complex (1) shows a reversible dehydration-rehydration behaviour, while complex (2) shows an irreversible dehydration-rehydration behaviour.

Synthesis, structure and properties of a new three-dimensional interpenetrated metal-organic framework with 3,3'-azodibenzoic acid (H2azdc) and 1,4-bis(1H-imidazol-1-yl)butane (bimb): {[Cd(azdc)(bimb)2]·H2O}n.

A new three-dimensional interpenetrated Cd(II)-organic framework based on 3,3'-azodibenzoic acid [3,3'-(diazenediyl)dibenzoic acid, H2azdc] and the auxiliary flexible ligand 1,4-bis(1H-imidazol-1-yl)butane (bimb), namely poly[[bis[µ2-1,4-bis(1H-imidazol-1-yl)butane-κ(2)N(3):N(3')][µ2-3,3'-(diazenediyl)dibenzoato-κ(2)O:O']cadmium(II)] monohydrate], {[Cd(C14H8N2O4)(C10H14N2)2]·H2O}n, (1), was obtained by a typical solution reaction in mixed solvents (water and N,N'-dimethylformamide). Each Cd(II) centre is six-coordinated by two O atoms of bis-monodentate bridging carboxylate groups from two azdc(2-) ligands and by four N atoms from four bimb ligands, forming an octahedral coordination environment. The Cd(II) ions are connected by the bimb ligands, resulting in two-dimensional (4,4) layers, which are further pillared by the azdc(2-) ligands, affording a threefold interpenetrated three-dimensional α-Po topological framework with the Schläfli symbol 4(12)6(3). The thermal stability and solid-state fluorescence properties of (1) have been investigated.