Multiomic meta-analysis suggests a correlation between steroid hormone-related genes and litter size in goats.

Litter size is a key indicator of production performance in livestock. However, its genetic basis in goats remains poorly understood. In this work, a genome-wide selection sweep analysis (GWSA) on 100 published goat genomes with different litter rates was performed for the first time to identify candidate genes related to kidding rate. This analysis was combined with the public RNA-sequencing data of ovary tissues (follicular phase) from high- and low-yielding goats. A total of 2278 genes were identified by GWSA. Most of these genes were enriched in signaling pathways related to ovarian follicle development and hormone secretion. Moreover, 208 differentially expressed genes between groups were obtained from the ovaries of goats with different litter sizes. These genes were substantially enriched in the cholesterol and steroid synthesis signaling pathways. Meanwhile, the weighted gene co-expression network was used to perform modular analysis of differentially expressed genes. The results showed that seven modules were reconstructed, of which one module showed a very strong correlation with litter size (r = -0.51 and p-value <0.001). There were 51 genes in this module, and 39 hub genes were screened by Pearson's correlation coefficient between core genes > 0.4, correlation coefficient between module members > 0.80 and intra-module connectivity ≥5. Finally, based on the results of GWSA and hub gene Venn analysis, seven key genes (ACSS2, HECW2, KDR, LHCGR, NAMPT, PTGFR and TFPI) were found to be associated with steroid synthesis and follicle growth development. This work contributes to understanding of the genetic basis of goat litter size and provides theoretical support for goat molecular breeding.

Progress on deer genome research.

Deer family is one of the most abundant mammalian families in the world. Deer species are distributed in wide geographic ranges including the North Pole, tropical regions and high-altitude mountains. Of these deer species, China accounts for more than 40% of them and is the main site for deer evolution. Besides the common phenotypical attributes for ruminants, deer family is evolved to possess the unique head gears with periodic regeneration, i.e. antlers. It is currently well accepted that deer is a very valuable model for the studies of ecology, behavior, evolution and biology, especially for the study of mammalian organ regeneration. Reference deer genome is the basis for systematically illustrating deer evolution, deciphering unique biological attributes of deer species, and is significant in protection and utilization of deer genetic resources. In this review, we summarize the recent progress in the field of deer genome research, including data of deer genetic variation, molecular basis of adaptive evolution, and key genes and functional genomics involved in deer antler origin and evolution. The overall aim of the paper is to provide the reference neccessary for in depth investigation of deer species.

Follistatin-like protein 1 (FSTL1) promotes chondrocyte expression of matrix metalloproteinase and inflammatory factors via the NF-κB pathway.

BACKGROUND: The expression of follistatin-like protein 1 (FSTL1) is closely associated with diseases of the musculoskeletal system. However, despite being a well characterized inflammatory mediator, the effects of FSTL1 on chondrocytes are not completely understood. In this study, we investigated the effects of FSTL1 on the expression of inflammatory and catabolic factors in rat chondrocytes. METHODS: Rat chondrocytes were treated directly with various concentrations of FSTL1 in vitro. The levels of matrix metalloproteinases (MMPs), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-1ß, tumour necrosis factor (TNF)-α and IL-6 were measured by polymerase chain reaction, ELISA and Western blotting. In addition, activation of the nuclear factor kappa B (NF-κB) pathway was explored to identify potential regulatory mechanisms. RESULTS: Follistatin-like protein 1 directly increased the expression of MMP-1, MMP-13, iNOS, COX-2, IL-1ß, TNF-α and IL-6 at both gene and protein level in a dose-dependent manner. Activation of NF- κB and phosphorylation of p65 were also promoted by FSTL1 stimulation. CONCLUSIONS: Follistatin-like protein 1 exerts pro-inflammatory and catabolic effects on cultured chondrocytes via activation of the NF-κB signalling pathway. FSTL1 may therefore be a target in the treatment of OA.

Production of bioactive metabolites by submerged fermentation of the medicinal mushroom Antrodia cinnamomea: recent advances and future development.

Edible and medicinal mushrooms have usually been considered as a sustainable source of unique bioactive metabolites, which are valued as promising provisions for human health. Antrodia cinnamomea is a unique edible and medicinal fungus widespread in Taiwan, which has attracted much attention in recent years for its high value in both scientific research and commercial applications owing to its potent therapeutic effects, especially for its hepatic protection and anticancer activity. Due to the scarcity of the fruiting bodies, the cultivation of A. cinnamomea by submerged fermentation appears to be a promising substitute which possesses some unique advantages, such as short culture time period and its high feasibility for scale-up production. However, the amount of fungal bioactive metabolites derived from the cultured mycelia of A. cinnamomea grown by submerged fermentation is much less than those obtained from the wild fruiting bodies. Hence, there is an urgent need to bridge such a discrepancy on bioactive metabolites between the wild fruiting bodies and the cultured mycelia. The objective of this article is to review recent advances and the future development of the mycelial submerged fermentation of A. cinnamomea in terms of enhancement for the production of fungal bioactive components by the optimization of culture conditions and the regulation of fungal metabolism. This review provides valuable information for further biotechnological applications of A. cinnamomea as well as other mushrooms being the source of bioactive ingredients by submerged fermentation.

Leonurine Exerts Anti-Catabolic and Anti-Apoptotic Effects via Nuclear Factor kappa B (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) Signaling Pathways in Chondrocytes.

BACKGROUND Leonurine confers neuroprotection, inhibits myocardial apoptosis, ameliorates endothelial dysfunction, and shows anti-inflammatory effects, and may be beneficial for clinical applications. However, the effects of leonurine on chondrocytes remain unknown. Here, we investigated the protective role of leonurine in rat chondrocytes. MATERIAL AND METHODS To explore the potential therapeutic effect of leonurine against osteoarthritis (OA), rat chondrocytes were treated with IL-1ß along with different concentrations of leonurine in vitro. The levels of matrix metalloproteinases (MMPs), ADAMTS, Bax, and Bcl-2 were measured by PCR, ELISA, and Western blotting. Caspase-3 activity in chondrocytes was determined using a caspase-3 activity assay. Western blotting was also performed to examine activation of the NF-kappaB and mitogen-activated protein kinase (MAPK) pathways to elucidate the likely regulatory mechanisms. RESULTS Leonurine counteracted IL-1ß-induced production of MMP-1, MMP-13, ADAMTS-4, and ADAMTS-5. Leonurine treatment reduced both the mRNA and protein levels of Bax and increased the level of Bcl-2. Leonurine also inhibited the activity of caspase-3 in IL-1ß-induced chondrocytes. Furthermore, the activation of MAPK and phosphorylation of p65 were suppressed by leonurine. CONCLUSIONS The results of this study indicate that leonurine exerts anti-catabolic and anti-apoptotic effects in chondrocytes in vitro via suppression of the NF-kappaB and MAPK signaling pathways.

Rosmarinic acid down-regulates NO and PGE2 expression via MAPK pathway in rat chondrocytes.

Rosmarinic acid (RosA) is a water-soluble polyphenol, which can be isolated from many herbs such as orthosiphon diffuses and rosmarinus officinalis. Previous studies have shown that RosA possesses various biological properties. In this study, we investigate the anti-osteoarthritic effects of RosA in rat articular chondrocytes. Chondrocytes were pre-treated with RosA, followed by the stimulation of IL-1ß. Real-time PCR and Western blot were performed to detect the expression of matrix metalloproteinase (MMP)-1, MMP-3 and MMP-13. Nitric oxide and PGE2 production were measured by Griess reagent and enzyme-linked immunosorbent assay (ELISA). The expression of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) was also investigated by Western blot analysis. We found that RosA down-regulated the MMPs expression as well as nitric oxide and PGE2 production in IL-1ß-induced chondrocytes. In addition, RosA inhibited p38 and JNK phosphorylation as well as p65 translocation. The results suggest that RosA may be considered a possible agent in the treatment of OA.

Diagnostic performance of computed tomography angiography in the detection of coronary artery in-stent restenosis: evidence from an updated meta-analysis.

OBJECTIVES: To evaluate the performance of computed tomography angiography (CTA) ≥64 slices for detecting coronary in-stent restenosis (ISR) and determine the influence of separate characteristics on diagnostic accuracy. METHODS: We searched the PubMed, EMBASE and Cochrane databases for studies of CTA ≥64 slices in diagnosing ISR. We pooled data on bivariate modelling, and subgroup analysis was also performed. RESULTS: A total of 35 studies involving 4131 stents were included. The pooled positive likelihood ratio (LR+) and the negative likelihood ratio (LR-) were 14.0 and 0.10, for CTA in diagnosis-significant ISR ≥50%. LR+ and LR- were similar between CTA >64 slices versus 64 slices (both P > 0.99). LR- (0.10) was good for ruling out suspected ISR for <3-mm diameter. Time between CTA and stent implantation >6 months did not affect the ability of CTA for the high LR+ (12.3) and the LR- (0.10). Thick-strut stents ≥100 µm or bifurcation stenting demonstrated inferior accuracy, which was unfavourable for stent imaging. CONCLUSIONS: With the high LR+ and LR- of CTA, patients with ISR may be appropriate for non-invasive angiographic follow-up. However, CTA imaging seems unsuitable for patients with characteristics unfavourable for stent imaging, such as thick-strut stents or bifurcation stenting. KEY POINTS: • CTA may provide accurate information on characteristics of in-stent restenosis lesions. • Using CTA, ISR patients may be appropriate for non-invasive angiographic follow-up. • Stent diameter and the number of slices do not influence CTA. • CTA seems unsuitable for patients with thick-strut stents or bifurcation stenting.

Structural Analysis of the Catalytic Mechanism and Substrate Specificity of Anabaena Alkaline Invertase InvA Reveals a Novel Glucosidase.

Invertases catalyze the hydrolysis of sucrose to glucose and fructose, thereby playing a key role in primary metabolism and plant development. According to the optimum pH, invertases are classified into acid invertases (Ac-Invs) and alkaline/neutral invertases (A/N-Invs), which share no sequence homology. Compared with Ac-Invs that have been extensively studied, the structure and catalytic mechanism of A/N-Invs remain unknown. Here we report the crystal structures of Anabaena alkaline invertase InvA, which was proposed to be the ancestor of modern plant A/N-Invs. These structures are the first in the GH100 family. InvA exists as a hexamer in both crystal and solution. Each subunit consists of an (α/α)6 barrel core structure in addition to an insertion of three helices. A couple of structures in complex with the substrate or products enabled us to assign the subsites -1 and +1 specifically binding glucose and fructose, respectively. Structural comparison combined with enzymatic assays indicated that Asp-188 and Glu-414 are putative catalytic residues. Further analysis of the substrate binding pocket demonstrated that InvA possesses a stringent substrate specificity toward the α1,2-glycosidic bond of sucrose. Together, we suggest that InvA and homologs represent a novel family of glucosidases.

Screening weight related genes of velvet antlers by whole genome re-sequencing.

The velvet antler is a special organ that has important biological significance for deer, and its growth is a complicated biological metabolism process. Growing evidence suggests that genetics factors play essential roles in the weight of velvet antlers. In this study, we investigated five sika deer (Cervus nippon) populations under the same feeding condition, and screened genetic variations in the 100 samples (including 50 heavy and 50 light velvet antler weight samples) by whole genome re-sequencing. The results showed that 94 genetic variations were related to the velvet antler weight, among which two single nucleotide polymorphism (SNP) sites were located on the exon regions of OAS2 and ALYREF/THOC4, respectively. Furthermore, ALYREF/THOC4 is highly expressed in the velvet antler. The biological functions of these genetic variations were highly related to the growth and development of deer velvet antlers. Collectively, we screened genes related to the velvet antler weight in sika deer populations by whole genome re-sequencing and identified 94 sites as candidate genetic variations related to the velvet antler weight. We hope that it will contribute to further mechanistic studies of velvet antler development and weight variations.

Acacetin inhibits expression of matrix metalloproteinases via a MAPK-dependent mechanism in fibroblast-like synoviocytes.

It is well known that rheumatoid arthritis (RA) is an autoimmune joint disease in which fibroblast-like synoviocytes (FLSs) play a pivotal role. In this study, we investigated the anti-arthritic properties of acacetin in FLSs. The expression of matrix metalloproteinase (MMP)-1, MMP-3 and MMP-13 were investigated by quantitative RT-PCR and western blot at gene and protein levels. At the same time, the phosphorylation of mitogen-activated protein kinases (MAPK) was investigated. The DNA-binding activity of NF-κB was investigated by electrophoretic mobility shift assay. We found that acacetin inhibits p38 and JNK phosphorylation and reduces MMP-1, MMP-3 and MMP-13 expression in interleukin-1ß-induced FLSs. Our results suggest that acacetin has antiarthritic effects in FLSs. Thus, acacetin should be further studied for the treatment of arthritis.

Baicalein Inhibits MMPs Expression via a MAPK-Dependent Mechanism in Chondrocytes.

BACKGROUND: Baicalein is a flavonoid isolated from Scutellaria baicalensis Georgi. Here, we investigated the anti-osteoarthritic effect of baicalein in vitro and in vivo. METHODS: Interleukin-1 beta (IL-1ß)-induced chondrocytes were treated with different concentrations of baicalein, real-time PCR and ELISA were performed to detect the matrix metalloproteinases (MMPs) expression. Western blot was used to evaluate the mitogen-activated protein kinase (MAPK) expression. In experimental osteoarthritis (OA), rabbits were treated with baicalein, gross morphological and histological assessment was performed to evaluate the cartilage damage. RESULTS: Baicalein significantly reduced the expression of MMPs in vitro and in vivo. Moreover, baicalein significantly reduced the phosphorylation of p38 and extracellular signal regulated kinase (ERK), but not of c-Jun N-terminal kinase (JNK). In addition, intra-articular injection of baicalein ameliorated the cartilage damage in a rabbit model of OA induced by anterior cruciate ligament transection (ACLT). CONCLUSIONS: The results indicate that baicalein may be considered as a potential agent for OA treatment.

Designing Symmetric Gradient Honeycomb Structures with Carbon-Coated Iron-Based Composites for High-Efficiency Microwave Absorption.

The impedance matching of absorbers is a vital factor affecting their microwave absorption (MA) properties. In this work, we controllably synthesized Material of Institute Lavoisier 88C (MIL-88C) with varying aspect ratios (AR) as a precursor by regulating oil bath conditions, followed by one-step thermal decomposition to obtain carbon-coated iron-based composites. Modifying the precursor MIL-88C (Fe) preparation conditions, such as the molar ratio between metal ions and organic ligands (M/O), oil bath temperature, and oil bath time, influenced the phases, graphitization degree, and AR of the derivatives, enabling low filler loading, achieving well-matched impedance, and ensuring outstanding MA properties. The MOF-derivatives 2 (MD2)/polyvinylidene Difluoride (PVDF), MD3/PVDF, and MD4/PVDF absorbers all exhibited excellent MA properties with optimal filler loadings below 20 wt% and as low as 5 wt%. The MD2/PVDF (5 wt%) achieved a maximum effective absorption bandwidth (EAB) of 5.52 GHz (1.90 mm). The MD3/PVDF (10 wt%) possessed a minimum reflection loss (RLmin) value of - 67.4 at 12.56 GHz (2.13 mm). A symmetric gradient honeycomb structure (SGHS) was constructed utilizing the high-frequency structure simulator (HFSS) to further extend the EAB, achieving an EAB of 14.6 GHz and a RLmin of - 59.0 dB. This research offers a viable inspiration to creating structures or materials with high-efficiency MA properties.

[Severity Differences and Mechanisms of Algal Blooms Among Sections in Pengxi River of the Three Gorges Reservoir].

Since the impoundment of the Three Gorges Dam, 50% of the first-order tributaries in the reservoir area have had frequent algal blooms but with variations regarding the geographical locations of the seriously bloomed sections and the scope of the latter being influenced by the mainstream. This study took the Pengxi River, a first-order tributary of the reservoir area, as an example in order to explore the difference in eutrophication among the river sections and the influence of the Yangtze River on its tributaries. During the spring bloom season of 2019, sampling was carried out in one-week intervals for a total duration of one month. Seven sampling sections (PX1-PX7) were set up from the confluence to upstream. According to the profiles of vertical water temperature and conductivity of each section, the influence scope and form of the backwater of the Yangtze River were inferred; in addition, severity differences and mechanisms of algal blooms among sections were explored through the comparison of the hydrology, water quality, and sediment nutrients among Gaoyang Lake (PX5), which has had serious algal blooms, and the upstream (PX6) and downstream (PX4) sections of PX5, which are both 4 km away from PX5. The results showed that during the sampling month, the average ρ(Chl-a) in the confluence area of the Pengxi River (PX1-PX4) and in the upstream (PX5-PX7) were in the range of 14.55-44.00 µg·L-1 and 42.66-175.40 µg·L-1, respectively. The ρ(Chl-a) of PX5 was up to 413.00 µg·L-1, which was significantly higher than that of other sections (P<0.05). Temperature and conductivity results showed that the backwater from Yangtze River flowed into the Pengxi River from the middle and bottom layers during the period from April to May. The confluence (PX1-PX4) sections were in the intersection area of the backwater from Yangtze River and the upstream of the Pengxi River; thus, the waterbody was unstable, which was not conducive to the formation of algal blooms. However, the upstream (PX5-PX7) sections were not directly affected by the backwater from Yangtze River, leading the nutrient exchange mainly vertically. Most averages of n(TN)/n(TP) and n(DTN)/n(DTP) of PX4-PX6 were all greater than 16, indicating a phosphorus-limited state. During sampling, the average sediment total phosphorus of PX5 was 91% of that in upstream PX6, which was only 4 km away, whereas the surface water total phosphorus of PX5 was 180% of that in PX6. The important reason for this phenomenon is that the water surface width of PX5 was 3.6-4.7 times that of PX6, indicating longer wind fetch in the former section. Owing to the mountainous landscape in the Three Gorges Reservoir (TGR) region where windy weather is rare, the disturbance effect of wind and waves on PX5 was stronger than that of PX6, and the nutrients released from the sediment at the PX5 section caused by wind and waves resupplied the surface water more easily, causing more serious algal blooms at PX5 than those at the remaining sections in the Pengxi River. The main causes of the algal blooms in the tributaries of the TGR area lied in the stability of water stratification and the supply of internal phosphorus. The stability of water stratification was mainly affected by the backwater from Yangtze River, and the supply of internal phosphorus in the algal bloom season was affected by the special water stratification phenomenon of the tributaries of TGR-the "surface density layers." The duration and degree of weather disturbance to the surface density layers can be used to predict the time and scale of algal blooms.

Integration of RNA-Seq and Machine Learning Identifies Hub Genes for Empagliflozin Benefitable Heart Failure with Reduced Ejection Fraction.

Purpose: This study aimed to analyze the hub genes of heart failure with reduced ejection fraction (HFrEF) treated with Empagliflozin using RNA sequencing (RNA-seq) and bioinformatics methods, including machine learning. Methods: From February 2021 to February 2023, nine patients with HFrEF were enrolled from our hospital's cardiovascular department. In addition to routine drug treatment, these patients received 10 mg of Empagliflozin once daily for two months. Efficacy was assessed and RNA-seq was performed on peripheral blood before and after treatment with empagliflozin. HFrEF-related hub genes were identified through bioinformatics analyses including differential gene expression analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, immune infiltration analysis, machine learning, immune cell correlation analysis and clinical indicator correlation analysis. Results: The nine patients included in this study completed a two-month treatment regimen, with an average age of 62.11 ± 6.36 years. By performing bioinformatics analysis on the transcriptome from the treatment groups, 42 differentially expressed genes were identified, with six being up-regulated and 36 being down-regulated (|log2FC|>1 and adj.pvalue<0.05). Immune infiltration analysis of these genes demonstrated a significant difference in the proportion of plasma between the pre-treatment and post-treatment groups (p<0.05). Two hub genes, GTF2IP14 and MTLN, were finally identified through machine learning. Further analysis of the correlation between the hub genes and immune cells suggested a negative correlation between GTF2IP14 and naive B cells, and a positive correlation between MTLN and regulatory T cells and resting memory CD4+ T cells (p<0.05). Conclusion: Through RNA-seq and bioinformatics analysis, this study identified GTF2IP14 and MTLN as the hub genes of HFrEF, and their mechanisms may be related to immune inflammatory responses and various immune cells.

Identification of Key Immune-Related Genes in the Treatment of Heart Failure After Myocardial Infarction with Empagliflozin Based on RNA-Seq.

Purpose: Heart failure is a serious complication after acute myocardial infarction (AMI). It is crucial to investigate the mechanism of action of empagliflozin in the treatment of heart failure. Methods: A total of 20 wild type (WT) male C57BL6/J mice were used to establish a model of heart failure after myocardial infarction and randomly divided into 2 groups: treatment group and control group. The treatment group was treated with empagliflozin, and the control group was treated with placebo. After 8 weeks of treatment, mouse heart tissues were collected for next generation sequencing. Bioinformatics methods were used to screen the key genes. Finally, the correlation between clinical data and gene expression was analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression of key genes. Results: A mouse model of heart failure was successfully constructed. By DEG analysis, a total of 740 DEGs in the treatment group vs the control group were obtained. Dendritic cells, granulocytes, follicular B, plasma cell, cDC1, cDC2, pDC and neutrophils were 8 different immune cells identified by immunoinfiltration analysis. Through WGCNA, the turquoise module with the highest correlation with the above differential immune cells was selected. One hundred and forty-two immune-related DEGs were obtained by taking intersection of the DEGs and the genes of the turquoise module. Col17a1 and Gria4 were finally screened out as key immune-related genes via PPI analysis and machine learning. Col17a1 was significantly up-regulated, while Gria4 was significantly down-regulated in the treatment group. At the same time, the expression level of Col17a1 was significantly correlated with left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS) and left ventricular internal dimension systole (LVIDs). Conclusion: Col17a1 and Gria4 are key immune-related genes of empagliflozin in the treatment of heart failure after myocardial infarction. This study provides a scientific basis for elucidating the mechanism of action of empagliflozin in treating heart failure after myocardial infarction.

Effects of exogenous melatonin on growth and physiological characteristics of Agropyron mongolicum seedlings under drought stress.

To clarify the alleviation effect of exogenous melatonin (MT) on Agropyron mongolicum under drought stress, we examined the response of A. mongolicum 'Yanchi' seedlings to simulated drought stress with polyethylene glycol 6000 (PEG-6000), by investigating the effects of exogenous addition of different concentrations (0, 1, 10, 50, 100, 150 and 200 mg·L-1) of MT on seedlings growth and physiological characteristics under drought stress. The results showed that drought stress significantly inhibited the growth of A. mongolicum seedlings, and that exogenous addition of different concentrations of MT could alleviate the growth inhibition caused by drought stress, with the strongest mitigation effect observed at MT concentration of 100 mg·L-1. Compared with the drought stress treatment alone, exogenous addition of 100 mg·L-1 MT under drought stress increased plant height, aboveground dry weight, and leaf relative water content by 58.2%, 121.2% and 48.1%. The contents of chlorophyll a, chlorophyll b, carotenoids increased by 48.7%, 80.8% and 38.3%, superoxide dismutase, peroxidase and root activity increased by 12.6%, 33.9% and 39.1%, and the contents of ascorbic acid and glutathione increased by 19.5% and 18.3%, respectively. The contents of proline, soluble sugar and soluble protein were increased by 16.2%, 32.6% and 14.3%, while that of malondialdehyde, hydrogen peroxide and superoxide anion radical were decreased by 45.8%, 65.8% and 30.8%, respectively. In summary, exogenous addition of 100 mg·L-1 MT could improve drought tolerance of A. mongolicum seedlings by promoting growth, enhancing antioxidant capacity, increasing the content of osmoregulation substances, inhibiting the excessive production of reactive oxygen, and reducing membrane peroxide level.

2-Hy-droxy-ethanaminium 2-methyl-5-nitro-benzene-sulfonate.

In the crystal structure of the title salt, C(2)H(8)NO(+)·C(7)H(6)NO(5)S(-), the cations and anions are linked together by N-H⋯O and O-H⋯O hydrogen bonds, forming layers parallel to (100). The plane of nitro group is skew with respect to the plane of benzene ring, making a dihedral angle of 17.5 (2)°.

The emerging role of adipokines in osteoarthritis: a narrative review.

Osteoarthritis (OA) is a most common multifactorial degenerative joint disease in elderly individuals. OA is affecting severely the quality of life of patients, while the causes of OA are not completely understood. Age, obesity, the female sex, and previous injury are considered as significant risk factors. Recently, increased levels of adipokines which are mainly produced by adipocytes have been detected in patients with osteoarthritis. Moreover, studies on different adipokines all reveal that they have played proinflammatory and catabolic/anabolic roles during the pathophysiology of OA. In the present review, we summarize current data on the effect of the adipose tissue-derived hormones leptin, adiponectin, resistin and visfatin on initiation and progression of OA.

Sphingosine-1-phosphate: a potential therapeutic target for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, which has as its primary target, the synovial tissues and articular cartilage. The current pharmacological treatment of RA includes non-steroidal anti-inflammatory drugs, corticosteroids, and disease-modifying anti-rheumatic drugs. Newer biological agents that work by inactivation of proinflammatory cytokines are available for treatment of RA. Sphingosine-1-phosphate (S1P) is a bioactive lipid that is generated from phosphorylation of sphingosine by activation of sphingosine kinase, and has been implicated as an important mediator in pathophysiological processes, including cell growth, differentiation, migration and survival, and angiogenesis. Several studies have explored the role of S1P in the pathogenesis of RA. The aim of this article was to review the biology and distribution of S1P, together with its role in RA, and to discuss its potential as a therapeutic target for RA.

Trichostatin A inhibits expression of cathepsins in experimental osteoarthritis.

The aim of this study was to investigate the effects of trichostatin A (TSA) on expression of cathepsins in cartilage in experimental osteoarthritis (OA). OA was induced in 18 rabbits by bilateral anterior cruciate ligament transection (ACLT). Four weeks after surgery, rabbits received intra-articular injection with TSA dissolved in the dimethylsulphoxide (DMSO) in the right knees and DMSO in the left knees once a week for 5 weeks. Rabbits were killed 7 days after the last injection. The knee joints were assessed by morphological and histological examination. Messenger RNA expression of cathepsins K, B, L, S and cystatin C was studied by real-time PCR. TSA inhibited the expression of cathepsins K, B, L, S and cystatin C accompanied with the less degradation in cartilage. The results suggest that TSA exhibits protective effects against cartilage degradation in rabbits with OA and the effects may be associated with the inhibition of cathepsins.