Abnormal lipid metabolism, such as systemic increased free fatty acid, results in overproduction of pro‐inflammatory enzymes and cytokines, which is crucial in the development of obesity‐related osteoarthritis (OA). However, there are only a few drugs that target the lipotoxicity of OA. Recent researches have documented that the traditional Chinese medicine, Sparstolonin B (Ssn B), exerted anti‐inflammatory effects in various diseases, but not yet in OA. On the basis of this evidence, our works purposed to evaluate the effect of Ssn B on free fatty acid (FFA) palmitate (PA)‐stimulated human osteoarthritic chondrocytes and obesity‐associated mouse OA model. We found that Ssn B suppressed PA‐triggered inflammatory response and extracellular matrix catabolism in a concentration‐dependent approach. In vivo, Ssn B treatment inhibited cartilage degeneration and subchondral bone calcification caused by joint mechanical imbalance and alleviated metabolic inflammation in obesity. Mechanistically, co‐immunoprecipitine and molecular docking analysis showed that the formation of tolllike receptor 4 (TLR4)/myeloid differentiation protein‐2 (MD‐2) complex caused by PA was blocked by Ssn B. Subsequently, it leads to inactivation of PA‐caused myeloid differentiation factor 88 (MyD88)‐dependent nuclear factor‐kappaB (NF‐κB) cascade. Together, these findings demonstrated that Ssn B is a potential treatment agent for joint degenerative diseases in obese individuals. 相似文献
The Revised International Staging System (R-ISS) is a simple and powerful prognostic tool for multiple myeloma (MM). However, heterogeneity in R-ISS stage is still poorly characterised, hampering improvement of treatments. We used single-cell RNA-seq to examine novel cellular heterogeneity and regular networks in nine MM patients stratified by R-ISS. Plasma cells were clustered into nine groups (P1–P9) based on gene expression, where P1–P5 were almost enriched in stage III.PDIA6 was significantly upregulated in P3 and LETM1 was enriched in P1, and they were validated to be upregulated in the MM cell line and in 22 other patients’ myeloma cells. Furthermore, in progression, PDIA6 was newly found and verified to be activated by UQCRB through oxidative phosphorylation, while LETM1 was activated by STAT1 via the C-type lectin receptor-signalling pathway. Finally, a subcluster of monocytes was exclusively found in stage III specifically expressed chemokines modulated by ATF3. A few ligand-receptor pairs (CCL3/CCL5/CCL3L1-CCR1) were obviously active in monocyte-plasma communications in stage III. Herein, this study identified novel molecules, networks and crosstalk pairs in different R-ISS stages of MM, providing significant insight for its prognosis and treatment.
Schistosomiasis remains a major public health problem in eastern China, particularly along the Yangtze River Basin. The latest national schistosomiasis control program (NSCP) was implemented in 2005 with the main goal of reducing the rate of infection to less than 5% by 2008 and 1% by 2015. To assess the progress, we applied a Bayesian spatio-temporal model to describe dynamics of schistosomiasis in Guichi, Anhui Province, China, using annual parasitological and environmental data collected within 41 sample villages for the period 2005–2011. Predictive maps of schistosomiasis showed that the disease prevalence remains constant and low. Results of uncertainty analysis, in the form of probability contour maps (PCMs), indicated that the first goal of “infection rate less than 5% by 2008” was fully achieved in the study area. More longitudinal data for schistosomiasis are needed for the assessment of the second goal of “infection rate less than 1% by 2015”. Compared with the traditional way of mapping uncertainty (e.g., variance or mean-square error), our PCMs provide more realistic information for schistosomiasis control. 相似文献
The current K-string-based protein sequence comparisons require large amounts of computer memory because the dimension of the protein vector representation grows exponentially with K. In this paper, we propose a novel concept, the “K-string dictionary”, to solve this high-dimensional problem. It allows us to use a much lower dimensional K-string-based frequency or probability vector to represent a protein, and thus significantly reduce the computer memory requirements for their implementation. Furthermore, based on this new concept, we use Singular Value Decomposition to analyze real protein datasets, and the improved protein vector representation allows us to obtain accurate gene trees. 相似文献
Caspases are cysteine proteases that play a critical role in the initiation and regulation of apoptosis. These enzymes act in a cascade to promote cell death through proteolytic cleavage of intracellular proteins. Since activation of apoptosis is implicated in human diseases such as cancer and neurodegenerative disorders, caspases are targets for drugs designed to modulate their action. Active caspases are heterodimeric enzymes with two symmetrically arranged active sites at opposite ends of the molecule. A number of crystal structures of caspases with peptides or proteins bound at the active sites have defined the mechanism of action of these enzymes, but molecular information about the active sites before substrate engagement has been lacking. As part of a study of peptidyl inhibitors of caspase-3, we crystallized a complex where the inhibitor did not bind in the active site. Here we present the crystal structure of the unoccupied substrate-binding site of caspase-3. No large conformational differences were apparent when this site was compared with that in enzyme-inhibitor complexes. Instead, the 1.9 A structure reveals critical side chain movements in a hydrophobic pocket in the active site. Notably, the side chain of tyrosine204 is rotated by approximately 90 degrees so that the phenol group occupies the S2 subsite in the active site. Thus, binding of substrate or inhibitors is impeded unless rotation of this side chain opens the area. The positions of these side chains may have important implications for the directed design of inhibitors of caspase-3 or caspase-7. 相似文献
The expression patterns of different genes encoding antioxidant enzymes and heat shock proteins were investigated, in present study, by real-time quantitative PCR in the hepatopancreas of abalone Haliotis discus hannai fed with different levels of dietary zinc (6.69, 33.8, 710.6 and 3462.5 mg/kg) for 20 weeks. The antioxidant enzymes include Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-superoxide dismutase (Mn-SOD), catalase (CAT), mu-glutathione-s-transferase (mu-GST) and thioredoxin peroxidase (TPx). The results showed that the mRNA expression of these antioxidant enzymes increased and reached the maximum at the dietary zinc level of 33.8 mg/kg, and then dropped progressively. Expression levels of the heat shock proteins (HSP26, HSP70 and HSP90) firstly increased at 33.8 mg/kg dietary Zn level, and reached to the maximum at 710.6 mg/kg, then dropped at 3462.5 mg/kg (p<0.05). Excessive dietary Zn (710.6 and 3462.5 mg/kg) significantly increases the Zn content and significantly decreases the total antioxidant capacity (T-AOC) in hepatopancreas (p<0.05). These findings showed that dietary Zn (33.8 mg/kg) could highly trigger the expression levels of antioxidant enzymes and heat shock proteins, but excessive dietary Zn (710.6 and 3462.5 mg/kg) induces a high oxidative stress in abalone. 相似文献
Photosynthesis is the most important chemical reaction in the world. The measurement of plant photosynthesis rate plays an important role in agriculture. Light-induced delayed fluorescence (DF) in plants is an intrinsic label of the efficiency of charge separation at P680 in photosystem II (PS II). In this paper, we have developed a biosensor that can accurately measure the plant photosynthesis ability by means of DF. Compared with common methods for measuring the photosynthesis rate based on consumption of CO2, the proposed technique can quantify the plant photosynthesis ability with less influence of the environment. The biosensor is an all-weather measuring instrument, it has its own illumination power and utilizes intrinsic DF as the measurement marker. The current investigation has revealed that, there is a good correspondence between the results measured by the biosensor and that by commercially available portable photosynthesis system under controlled conditions. We thus conclude that DF is an excellent marker for evaluating plant photosynthesis ability under its biological status with less interferences of the environment. 相似文献