ADAMTS4 and ADAMTS5 Knockout Mice Are Protected from Versican but Not Aggrecan or Brevican Proteolysis during Spinal Cord Injury

The chondroitin sulfate proteoglycans (CSPGs) aggrecan, versican, and brevican are large aggregating extracellular matrix molecules that inhibit axonal growth of the mature central nervous system (CNS). ADAMTS proteoglycanases, including ADAMTS4 and ADAMTS5, degrade CSPGs, representing potential targets for ameliorating axonal growth-inhibition by CSPG accumulation after CNS injury. We investigated the proteolysis of CSPGs in mice homozygous for Adamts4 or Adamts5 null alleles after spinal cord injury (SCI). ADAMTS-derived 50-60 kDa aggrecan and 50 kDa brevican fragments were observed in Adamts4−/−, Adamts5−/−, and wt mice but not in the sham-operated group. By contrast Adamts4−/− and Adamts5−/− mice were both protected from versican proteolysis with an ADAMTS-generated 70 kDa versican fragment predominately observed in WT mice. ADAMTS1, ADAMTS9, and ADAMTS15 were detected by Western blot in Adamts4−/− mice' spinal cords after SCI. Immunohistochemistry showed astrocyte accumulation at the injury site. These data indicate that aggrecan and brevican proteolysis is compensated in Adamts4−/− or Adamts5−/− mice by ADAMTS proteoglycanase family members but a threshold of versican proteolysis is sensitive to the loss of a single ADAMTS proteoglycanase during SCI. We show robust ADAMTS activity after SCI and exemplify the requirement for collective proteolysis for effective CSPG clearance during SCI

a New Alternative for Fish Oil Supplements

The proximate composition of male and female Leuciscus lepidus in Beyşehir Lake was investigated. The fatty acid profiles of total lipid, phospholipid, and triacylglycerol in muscle and liver of male and female L. lepidus were evaluated by gas chromatography. Proximate analyses showed that meat of male and female L. lepidus had 15.13 ± 0.04 and 18.75 ± 0.11% fat, 20.42 ± 0.45 and 22.21 ± 0.56% protein, 65.47 ± 1.37 and 61.28 ± 1.03% moisture, and 1.51 ± 0.05 and 1.50 ± 0.03% ash, respectively. The percentage of total saturated fatty acids was higher in liver than in muscle, whereas the total polyunsaturated fatty acid (PUFA) content was the lowest in all fatty acid profiles. The phospholipids contained more PUFAs than triacylglycerol. Analysis of variance indicated significant differences ( < 0.05) between male (47.51%) and female (49.98%) muscle PUFAs in total lipid. The proportion of omega 3 ( 3) to omega 6 ( 6) fatty acids of total lipid was 3.15 in male and 3.68 in female. The ratio is an important indicator for comparing the value of fish oil. Therefore, it was concluded that L. lepidus was considered to be a high quality product for healthy food choice. Additionally, female L. lepidus may especially be used to produce fish oil supplements from freshwater fish combined with vegetable oils

Caffeic Acid Phenethyl Ester as a Protective Agent against Nephrotoxicity and/or Oxidative Kidney Damage: A Detailed Systematic Review

Caffeic acid phenethyl ester (CAPE), an active component of propolis, has been attracting the attention of different medical and pharmaceutical disciplines in recent years because of its antioxidant, anti-inflammatory, antiproliferative, cytotoxic, antiviral, antifungal, and antineoplastic properties. One of the most studied organs for the effects of CAPE is the kidney, particularly in the capacity of this ester to decrease the nephrotoxicity induced by several drugs and the oxidative injury after ischemia/reperfusion (I/R). In this review, we summarized and critically evaluated the current knowledge regarding the protective effect of CAPE in nephrotoxicity induced by several special medicines such as cisplatin, doxorubicin, cyclosporine, gentamycin, methotrexate, and other causes leading to oxidative renal injury, namely, I/R models and senility

Caffeic Acid Phenethyl Ester As a Protective Agent Against Nephrotoxicity and/or Oxidative Kidney Damage: A Detailed Systematic Review

Caffeic acid phenethyl ester (CAPE), an active component of propolis, has been attracting the attention of different medical and pharmaceutical disciplines in recent years because of its antioxidant, anti-inflammatory, antiproliferative, cytotoxic, antiviral, antifungal, and antineoplastic properties. One of the most studied organs for the effects of CAPE is the kidney, particularly in the capacity of this ester to decrease the nephrotoxicity induced by several drugs and the oxidative injury after ischemia/reperfusion (I/R). In this review, we summarized and critically evaluated the current knowledge regarding the protective effect of CAPE in nephrotoxicity induced by several special medicines such as cisplatin, doxorubicin, cyclosporine, gentamycin, methotrexate, and other causes leading to oxidative renal injury, namely, I/R models and senility.PubMedWoSScopu

Effects of Silybum marianum Extract on High-Fat Diet Induced Metabolic Disorders in Rats

Silybum marianum extract (SME) has been used for centuries as a natural remedy for diseases of liver and biliary tract. Lately, it has been promoted as a nutritional supplement for beneficial effects on some risk factors of diabetes and hyperlipidemia. In this study we aimed to determine the effects of SME on high-fat diet (HFD) induced metabolic disorders. Male Sprague Dawley rats were fed HFD for 11 weeks to induce obesity. SME was given to animals for two different durations, for 11 weeks or for 7 weeks. The results showed significant increase in plasma transaminases, total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), leptin, high sensitive C-reactive protein (hsCRP), glucose and insulin along with significant increase in body mass index (BMI) and liver weights in rats fed the HFD diet compared to rats fed with standard rat diet. SME supplementation for different durations raised improvement in the HFD-induced metabolic disorders such as insulin resistance, hyperlipidemia and hepatopathy at different degrees. Our study concludes that SME can be well considered as an effective supplement to improve insulin and leptin sensitivity and hyperlipidemia and to suppress body weight gain

A disintegrin-like metalloproteinase with thrombospondin motif 8 expression analysis in OUMS-27 chondrosarcoma cells before and after insulin administration

12-16A disintegrin-like and metalloproteinase with thrombospondin motif 8 (ADAMTS8) is a secreted protease with anti-angiogenic properties. It inhibits vascular endothelial growth factor (VEGF) induced angiogenesis and suppresses fibroblast growth factor 2 (FGF-2) induced vascularization. Angiogenesis and extracellular matrix degradation are the key events in tumor progression, and ADAMTS8 is also known to be a member of the aggrecanases family. In the present study, we  investigated the expression levels of ADAMTS8 in chondrosarcoma cells to elucidate the effect of insulin on the tumor cells in terms of ADAMTS production. The OUMS-27 cells were cultured and separately exposed to 10 μmol/mL insulin up to 11 days in Dulbecco’s modified Eagle’s medium. After specific time limits (days 1, 3, 7, and 11), the culture was terminated and RNA was isolated using TRIzol reagent and converted to cDNA. The expression levels of ADAMTS8 were evaluated by qRT-PCR. The ADAMTS8 expression in OUMS-27 cells exhibited about 4-fold decrease following insulin treatment on day 11. Statistically significant differences were noted between the control and day 1 (P = 0.008), day 7 (P = 0.047) and day 11 (P = 0.008) groups. The effect of insulin on chondrosarcoma cells in terms of ADAMTS8 expression has not been reported earlier. The decrease in ADAMTS8 expression could be considered as a novel finding that has the potential to explain some pathophysiological mechanisms of tumor cells. Furthermore, the finding could also shed some light on the relationships between matrix degradation and insulin treatment in vitro

Adamts12 Depletion By Insulin In Oums-27 Human Chondrosarcoma Cells

Objectives: In this study, we aim to investigate the association between articular damage in diabetes and a disintegrin-like and metalloproteinase with thrombospondin motifs 12 (ADAMTS12) at gene expression and protein levels. Materials and methods: OUMS-27 human chondrosarcoma cells were used to investigate how ADAMTS12 levels changed in vitro condition in presence and absence of insulin. The study included three groups of cells treated with 10 mu g/mL of insulin, and a control group. Cells were incubated with insulin in medium for one day, three days, and seven days. The effects of insulin on ADAMTS12 were investigated at both gene expression and protein levels. The relationships between the variables were tested by Mann-Whitney U test. Results: ADAMTS12 expression was significantly lower in the groups treated with insulin medium for one day and seven day periods (p=0.008 and p=0.008, respectively) compared to the control group. No significant difference was detected in the expression level between the groups kept in insulin medium for three days and the control group (p=0.55). In addition, protein amounts of the groups exposed to insulin medium for one, three, and seven day periods were lower. Conclusion: Insulin reduces the amount of ADAMTS12 which causes delayed recovery of cartilage tissue in the OUMS-27 cell lines utilized in our study for their chondrocytic properties. This reduction due to insulin treatment may contribute to recovery of cartilage tissue.WoSScopu

Hydrogen Peroxide-Induced Oxidative Damage In Human Chondrocytes: The Prophylactic Effects Of Hypericum Perforatum Linn Extract On Deoxyribonucleic Acid Damage, Apoptosis And Matrix Remodeling By A Disintegrin-Like And Metalloproteinase With Thrombospondin Motifs Proteinases

Objectives: This in vitro study aimed to examine the protective roles of Hypericum perforatum Linn (HPL) extract on cell viability, DNA damage, apoptosis and a disintegrin-like and metalloproteinase with thrombospondin motifs (ADAMTS) proteins in chondrocytes induced by hydrogen peroxide (H2O2), as a model of chondrocytes subjected to reactive oxygen species attack in rheumatoid arthritis and osteoarthritis. Materials and methods: Human chondrosarcoma cell line (OUMS-27) was used. Cells were incubated with different concentrations of methanolic extract (100, 400, and 750 mu g/ml) of HPL for 36 hours, and then treated with 0.7 mM H2O2 for two hours. Trypan blue was used for evaluation of cell viability, while DNA damage was evaluated by alkaline Comet assay. Caspase-1, ADAMTS5, ADAMTS9, and glyceraldehyde-3-phosphate dehydrogenase proteins were analyzed by Western blot. Results: In vitro H2O2 treatment decreased OUMS-27 cell viability. Cells pretreated with HPL at concentration of 400 mu g/mL were best protected from H2O2 toxicity. Compared to 100 mu g/ml concentration, pretreatment of cells with 750 or 400 mu g/ml of HPL generated more protection against H2O2-induced DNA damage. Hydrogen peroxide application to the cells led to a slight increase in Caspase-1 expression, which shows no apoptosis. The most prominent increase in Caspase-1 level was shown in cells treated with 400 mu g/ml of HPL extract. There was an increase in ADAMTS9 and a decrease in ADAMTS5 levels upon H2O2 administration. Pretreatment with HPL led to more decrease in ADAMTS5 level, indicating the protection of extracellular matrix attacked by these proteinases in cartilage tissue. Conclusion: It can be concluded that HPL has a potential to reverse the negative effects and processes induced by H2O2 in OUMS-27 cells and it can protect the surrounding cartilage area of chondrocytes from oxidative damage, which is suggested to be one of the main molecular factors accused for progression of rheumatoid arthritis and osteoarthritis.WoSScopu

Female Leuciscus lepidus May Be a New Alternative for Fish Oil Supplements

The proximate composition of male and female Leuciscus lepidus in Beysehir Lake was investigated. The fatty acid profiles of total lipid, phospholipid, and triacylglycerol in muscle and liver of male and female L. lepidus were evaluated by gas chromatography. Proximate analyses showed that meat of male and female L. lepidus had 15.13 +/- 0.04 and 18.75 +/- 0.11\% fat, 20.42 +/- 0.45 and 22.21 +/- 0.56\% protein, 65.47 +/- 1.37 and 61.28 +/- 1.03\% moisture, and 1.51 +/- 0.05 and 1.50 +/- 0.03\% ash, respectively. The percentage of total saturated fatty acids was higher in liver than in muscle, whereas the total polyunsaturated fatty acid (PUFA) content was the lowest in all fatty acid profiles. The phospholipids contained more PUFAs than triacylglycerol. Analysis of variance indicated significant differences (P < 0.05) between male (47.51\%) and female (49.98\%) muscle PUFAs in total lipid. The proportion of omega 3 (omega 3) to omega 6 (omega 6) fatty acids of total lipid was 3.15 in male and 3.68 in female. The ratio is an important indicator for comparing the value of fish oil. Therefore, it was concluded that L. lepidus was considered to be a high quality product for healthy food choice. Additionally, female L. lepidusmay especially be used to produce fish oil supplements from freshwater fish combined with vegetable oils

The Investigation of ADAMTS16 in Insulin-Induced Human Chondrosarcoma Cells.

A disintegrin-like metalloproteinase with thrombospondin motifs (ADAMTS) is a group of proteins that have enzymatic activity secreted by cells to the outside extracellular matrix. Insulin induces proteoglycan biosynthesis in chondrosarcoma chondrocytes. The purpose of the present in vitro study is to assess the time course effects of insulin on ADAMTS16 expression in OUMS-27 (human chondrosarcoma) cell line to examine whether insulin regulates ADAMTS16 expression as well as proteoglycan biosynthesis with multifaceted properties or not