Role of crosstalk between synovial cells and chondrocytes in osteoarthritis (Review).

Osteoarthritis (OA) is a low-grade, nonspecific inflammatory disease that affects the entire joint. This condition is characterized by synovitis, cartilage erosion, subchondral bone defects, and subpatellar fat pad damage. There is mounting evidence demonstrating the significance of crosstalk between synovitis and cartilage destruction in the development of OA. To comprehensively explore the phenotypic alterations of synovitis and cartilage destruction, it is important to elucidate the crosstalk mechanisms between chondrocytes and synovial cells. Furthermore, the updated iteration of single-cell sequencing technology reveals the interaction between chondrocyte and synovial cells. In the present review, the histological and pathological alterations between cartilage and synovium during OA progression are described, and the mode of interaction and molecular mechanisms between synovial cells and chondrocytes in OA, both of which affect the OA process mainly by altering the inflammatory environment and cellular state, are elucidated. Finally, the current OA therapeutic approaches are summarized and emerging therapeutic targets are reviewed in an attempt to provide potential insights into OA treatment.

Application of radiomics model based on lumbar computed tomography in diagnosis of elderly osteoporosis.

A metabolic bone disease characterized by decreased bone formation and increased bone resorption is osteoporosis. It can cause pain and fracture of patients. The elderly are prone to osteoporosis and are more vulnerable to osteoporosis. In this study, radiomics are extracted from computed tomography (CT) images to screen osteoporosis in the elderly. Collect the plain scan CT images of lumbar spine, cut the region of interest of the image and extract radiomics features, use Lasso regression to screen variables and adjust complexity, use python language to model random forests, support vector machines, K nearest neighbor, and finally use receiver operating characteristic curve to evaluate the performance of the model, including precision, recall, accuracy and area under the curve (AUC). For the model, 14 radiolomics features were selected. The diagnosis performance of random forest model and support vector machine is good, all around 0.9. The AUC of K nearest neighbor model in training set and test set is 0.828 and 0.796, respectively. We selected the plain scan CT images of the elderly lumbar spine to build radiomics features model, which has good diagnostic performance and can be used as a tool to assist the diagnosis of osteoporosis in the elderly.

Chemiluminescence method based on the KIO4 -K2 CO3 -Mn2+ reaction for rapid and sensitive determination of forchlorfenuron in dried fruit.

Forchlorfenuron is a low-toxic phenylurea plant growth regulator. Excessive intake of forchlorfenuron can lead to metabolic disorders of the matrix and be harmful to human health. The chemiluminescence intensity of the KIO4 -K2 CO3 -Mn2+ reaction decreased in the presence of forchlorfenuron. Based on this result, a rapid and sensitive chemiluminescence method was established to determine forchlorfenuron by combining it with a batch injection static device. The injection speed, injection volume and reagent concentration of the forchlorfenuron-KIO4 -K2 CO3 -Mn2+ chemiluminescence reaction were optimized. Under these optimized conditions, the linear range of the method was 1.0-200.0 µg/L, and the limit of detection was 0.29 µg/L (S/N = 3). The chemiluminescence method for the determination of forchlorfenuron could be completed in 10 s. The method was applied to detect the residual forchlorfenuron in dried fruit samples, and the results are consistent with high-performance liquid chromatography-mass spectrometry. This method has the advantages of high sensitivity, rapid response, less reagent consumption, and convenient operation. It will provide a new perspective for chemiluminescence for the rapid and sensitive determination of forchlorfenuron in various complex samples.

Dihydro-Resveratrol Attenuates Oxidative Stress, Adipogenesis and Insulin Resistance in In Vitro Models and High-Fat Diet-Induced Mouse Model via AMPK Activation.

Management of obesity has become a prevalent strategy for preventing the diseases closely integrated with excess body weight such as diabetes over the last half century. Searching for therapeutic agents acting on oxidative stress, adipogenesis and insulin resistance is considered as an efficient approach to control obesity-related diseases. The present study was designed to examine the in vitro and in vivo effects of dihydro-resveratrol (DR2), a naturally occurring compound from Dendrobium medicinal plants, on oxidative stress aggravation, adipogenesis, lipogenesis and insulin sensitivity. We utilized an in vitro 3T3-L1 adipocyte differentiation model to show that DR2 could reduce pre-adipocyte maturation by activation of AMPK/SIRT1 signaling proteins to inhibit p38MAPK proteins. With the use of in vitro oxidative-stress-induced hepatocytes and myoblasts models, DR2 was also shown to be able to reduce oxidative stress aggravation through mediation of Nrf2-related antioxidative cascade, reduce intracellular lipid accumulation through phosphorylation of ACC protein, reduce lipid peroxidation in hepatocytes and promote insulin sensitivity via activation of AKT protein in the insulin-resistant HepG2 cells and C2C12 cells. The effects of DR2 on adipogenesis, lipid accumulation, insulin resistance and blood glucose clearance were further demonstrated in the high-fat diet-induced obesity mouse model. Our in vitro and in vivo studies determined that DR2 could contain therapeutic potential for the treatment of obesity and type 2 diabetes.

Improvement in the healing of bone fractures using a cyclodextrin/Ni-MOF nanofibers network: the development of a novel substrate to increase the surface area with desirable functional properties.

In this study, a ß-cyclodextrins (ß-CDs)/Ni-based MOF (ß-CDs/Ni-based MOF) fibrous network with focus on biocompatible and biodegradable properties was used as a new material for orthopedic applications. The final products were synthesized by an efficient, rapid, and controllable electrospinning route under optimal conditions, including a flow rate of 0.3 mL g-1, applied voltage of 18 kV, and spinning distance of 20 cm. Efficient characterization by various analyzes showed that the ß-CDs/Ni-based MOF fibrous nanostructures had a thermal stability at about 320 °C and homogeneous particles with a narrow size distribution. The BET analysis results showed a specific surface area of 2140 m2 g-1 for these compounds, which facilized potential conditions needed for the application of these compounds as a new substrate to improve the healing of bone fractures. The results showed the better porosity of the ß-CDs/Ni-based MOF scaffolds as an essential property, leading to higher proliferation and nutrition and oxygen delivery, resulting in more tissue regeneration. This study proposes a novel strategy for a fibrous network substrate with distinct properties for orthopedic purposes.

Role of macrophage polarization in osteoarthritis (Review).

Osteoarthritis (OA) is a disease involving the whole joint that seriously reduces the living standards of individuals. Traditional treatments include physical therapy, administration of anti-inflammatory and analgesic drugs and injection of glucocorticoids or hyaluronic acid into the joints. However, these methods have limited efficacy and it is difficult to reverse the progression of OA, therefore it is urgent to find new effective treatment methods. Immune microenvironment is significant in the occurrence and development of OA. Recent studies have shown that macrophages are important targets for the treatment of OA. Macrophages are polarized into M1 pro-inflammatory phenotype and M2 anti-inflammatory phenotype under stimulation of different factors, which release and regulate inflammatory response and cartilage growth. Accumulating studies have tried to alleviate OA by regulating macrophage homeostasis. The present study summarized the related studies, discuss the mechanism of various therapeutic reagents on OA, expound the molecular mechanism of drug effect on OA and attempted to provide clues for the treatment of OA.

Omics approach to reveal the effects of obesity on the protein profiles of the exosomes derived from different adipose depots.

BACKGROUND: Obesity affects the cargo packaging of the adipocyte-derived exosomes. Furthermore, adipocytes in different adipose tissues have different genetic makeup, the cargo contents of the exosomes derived from different adipose tissues under obesity conditions should be different, and hence their impacts on the pathophysiological conditions. METHODS AND RESULTS: iTRAQ-based quantitative proteomics show that obesity has more prominent effects on the protein profiles of the exosomes derived from subcutaneous adipose tissue (SAT-Exos) in the high fat diet-induced obesity (DIO) mice than those derived from epididymal adipose tissue (EAT-Exos) and visceral adipose tissue (VAT-Exos). The differentially expressed proteins (DEPs) in SAT-Exos and VAT-Exos are mainly involved in metabolism. Subsequent untargeted metabolomic and lipidomics analyses reveal that injection of these SAT-Exos into the B6/J-Rab27a-Cas9-KO mice significantly affects the mouse metabolism such as fatty acid metabolism. Some of the DEPs in SAT-Exos are correlated with fatty acid metabolism including ADP-ribosylation factor and mitogen-activated protein kinase kinase kinase-3. Pathway analysis also shows that SAT-Exos affect adipocyte lipolysis and glycerophospholipid metabolism, which is in parallel with the enhanced plasma levels of fatty acids, diglycerides, monoglycerides and the changes in glycerophospholipid levels in DIO mice. CONCLUSION: Our data provide scientific evidence to suggest SAT-Exos contribute to the changes in plasma lipid profiles under obesity conditions.

Discovery of a novel anti-obesity meroterpenoid agent targeted subcutaneous adipose tissue.

BACKGROUND: Meroterpenoid furanasperterpene A (T2-3) with a novel 6/6/6/6/5 pentacyclic skeleton was isolated from the Aspergillus terreus GZU-31-1. Previously, we showed that T2-3 possessed significant lipid-lowering effects in 3T3-L1 adipocytes at 5 µM concentration. However, its therapeutic effect in metabolic disease and the underlying mechanisms of action remain unclear. METHODS: High fat diet-induced obesity (DIO) mouse model and 3T3-L1 cell model were used to assess the anti-obesity effects of T2-3. Lipids in the adipocytes were examined by Oil Red O staining. ß-catenin expression was examined by immunofluorescence and Western blotting, its activity was assessed by TOPflash/FOPflash assay. RESULTS: T2-3 possessed potent anti-obesity effects in DIO mice, it significantly reduced body weight and subcutaneous adipose tissue (SAT) mass. Mechanistic studies showed that T2-3 significantly inhibited 3T3-L1 preadipocyte differentiation as indicated by the reduced number of mature adipocytes. The treatments also reduced the expressions of critical adipogenic transcription factors CEBP-α and PPAR-γ in both 3T3-L1 adipocytes and SAT in DIO mice. Interestingly, T2-3 increased the cytoplasmic and nuclear expressions of ß-catenin and the transcriptional activity of ß-catenin in 3T3-L1 adipocytes; the elevated ß-catenin expression was also observed in SAT of the T2-3-treated DIO mice. Indeed, upregulation of ß-catenin activity suppressed adipogenesis, while ß-catenin inhibitor JW67 reversed the anti-adipogenic effect of T2-3. Taken together, our data suggest that T2-3 inhibits adipogenesis by upregulating ß-catenin activity. CONCLUSIONS: Our study is the first report demonstrating meroterpenoid furanasperterpene A as a novel 6/6/6/6/5 pentacyclic skeleton (T2-3) that possesses potent anti-adipogenic effect by targeting ß-catenin signaling pathway. Our findings drive new anti-obesity drug discovery and provide drug leads for chemists and pharmacologists.

Magnetic porous carbons derived from iron-based metal-organic framework loaded with glucose for effective extraction of synthetic organic dyes in drinks.

The conversion of metal-organic frameworks (MOFs) to porous carbon has attracted extensive attention for developing multifunctional adsorbent materials. Herein, we demonstrated a facile method to prepare magnetic porous carbon via calcinating MIL-101(Fe) precursor loaded with glucose at 700 °C in an N2 atmosphere. The obtained magnetic porous carbon (MPCG) contained plenty of oxygen-containing functional groups and exhibited an enlarged specific surface area (177.7 m2/g) compared with its precursor (41.2 m2/g). In addition, MPCG can be easily separated from the matrix by a magnet. Benefitting from these advantages, the magnetic porous carbon exhibited high affinity toward four synthetic organic dyes (amaranth, ponceau 4R, sunset yellow, and lemon yellow) in an aqueous solution. Moreover, the adsorbent can be applied to quantitatively detect synthetic organic dyes in drinks coupled with chromatography. A new magnetic solid-phase extraction method for dye analysis yielded reasonable linearity (r â–¡ 0.99), low limits of detection (0.047-0.076 µg/L), and good precision within the analyte concentration range of 0.25-50 µg/L.

The impact of obesity on adipocyte-derived extracellular vesicles.

Recently, the emerging roles of adipocyte-derived extracellular vesicles (EVs) linking obesity and its comorbidities have been recognized. In obese subjects, adipocytes are having hypertrophic growth and are under stressed. The dysfunction adipocytes dysregulate the assembly of the biological components in the EVs including exosomes. This article critically reviews the current findings on the impact of obesity on the exosomal cargo contents that induce the pathophysiological changes. Besides, this review also summarizes the understanding on how obesity affects the biogenesis of adipocyte-derived exosomes and the exosome secretion. Furthermore, the differences of the exosomal contents in different adipose depots, and the impact of obesity on the exosomes that are derived from the stromal vascular fraction such as the adipose tissue macrophages and adipocyte-derived stem cells will also be discussed. The current development and potential application of exosome-based therapy will be summarized. This review provides crucial information for the design of novel exosome-based therapy for the treatment of obesity and its comorbidities.

Combination of Wogonin and Artesunate Exhibits Synergistic anti-Hepatocellular Carcinoma Effect by Increasing DNA-Damage-Inducible Alpha, Tumor Necrosis Factor α and Tumor Necrosis Factor Receptor-Associated Factor 3-mediated Apoptosis.

Hepatocellular carcinoma (HCC) is difficult to treat, and is the second leading cause of cancer-related death worldwide. This study aimed to examine whether combination of wogonin and artesunate exhibits synergistic anti-HCC effect. Our data show that the combination treatment exhibits synergistic effect in reducing HCC cell viability by increasing apoptosis as indicated by the elevated cleavage of caspase 8, 3 and PARP. Interestingly, PCR array and the subsequent studies indicate that the combination treatment significantly increases the expression of DNA-damage-inducible, alpha (GADD45A), tumor necrosis factor (TNFα) and TNF receptor-associated factor 3 (TRAF3). Knockdown of GADD45A, TNFα or TRAF3 abolishes the combination treatment-enhanced apoptosis and the synergistic effect in reducing HCC cell viability. In the HCC-bearing xenograft mouse models, although the combination treatment increases the activity of NFκB in the tumor tissues, it exhibits a more potent anti-HCC effect than the mono-treatment, which may due to the enhanced apoptosis as indicated by the increased expression of GADD45A, TNFα, TRAF3 and apoptotic markers. Our study clearly demonstrates that the combination of artesunate and wogonin exhibits synergistic anti-HCC effect, and support the further development of this combination as alternative therapeutics for HCC management.