Evaluation of protein and lipid oxidative stress in the patients with postmenopausal osteoporosis

Objective: Oxidative stress may change cellular function in multiple pathological conditions, including osteoporosis. We aimed to determine malondialdehyde (MDA) levels, advanced oxidation protein pruducts (AOPP), levels end products of protein oxidation, thiol as known antioxidant, serum paraoxonase 1 (PON1) activities as known lipid antioxidant, induced by reactive oxygen species (ROS) for evaluating oxidative stress in osteoporotic patients. Methods: 59 patients diagnosed with postmenopaual osteoporosis were included in the study and compared with 21 healthy controls. Serum AOPP, MDA, thiol levels and PON1 activity were measured according to an enzymatic spectrophotometric method. Results: The serum MDA, AOPP, and thiol levels was significantly higher in the patient group than controls (p<0.05). PON1 activity was found lower in the patients group than the control group. Conclusion: Increased ROS levels in osteoporotic patients may result in a pro-oxidation environment, which in turn could result in increased MDA, AOPP. As a result, lipid peroxidation and protein oxidation may have a role in the pathogenesis of the osteoporotic patients

Macrolipasemia secondary to colon cancer chemotherapy: a case report

We reported macrolipasemia in a colon cancer patient during the chemotherapy period without any evidence of pancreatitis. A 52-year-old man formerly treated for papillary thyroid carcinoma had elevated a carcinoembryonic antigen (CEA) concentration in the latest control and was diagnosed with colon cancer. Xelox chemotherapy (oxaliplatin and capecitabine) protocol was planned for six months. Interestingly, the lipase activities gradually increased from 30 U/L to 434 U/L, and exceeded three times the upper limit of the reference range (13-60 U/L). There were no symptoms of pancreatitis, and the abdominal computed tomography (CT) scan was also normal. Polyethylene glycol (PEG) recovery % values of serum samples gradually decreased and were 27% in the recent sample before the end of chemotherapy. Interestingly, the serum lipase activity fell a month after chemotherapy, and PEG recovery % increased (39%). We considered the following possibilities: (1) macrolipasemia due to chemotherapy drugs, (2) macrolipasemia due to antibodies against chemotherapy drugs

Suberoylanilide Hydroxamic Acid (SAHA) Reduces Fibrosis Markers and Deactivates Human Stellate Cells via the Epithelial-Mesenchymal Transition (EMT)

Hepatic fibrosis is known as the accumulation of connective tissue secondary to chronic damage to the liver. Epithelial-mesenchymal transition (EMT) corresponding increase in liver fibrogenesis was shown with immunohistochemistry and PCR-based studies. Suberoylanilide hydroxamic acid (SAHA), a synthetic compound approved as a histone deacetylase inhibitor (HDAC) by the FDA to treat cutaneous T-cell lymphoma is under investigation for the treatment of lung and renal fibrosis. Experimental modeling for hepatic fibrosis can be constructed with an LX2 cell line isolated from human hepatic stellate cells (HSCs). In this study, we aimed to investigate the modulation of SAHA in the pathogenesis of liver fibrosis by detecting the levels of proteins; (E-cadherin (E-cad), N-cadherin (N-cad), Vimentin (Vim), and genes; E-cad, N-cad, Vim, transforming growth factor-beta (TGF-beta), alpha-smooth muscle actin (alpha-SMA), type 1 collagen (COL1A1), type 3 collagen (COL3A1)) that play a significant role in EMT with the LX2 cell line. We also evaluated the action of SAHA with cell proliferation, clonogenic, and migration assay. Cell proliferation was performed by flow cytometry. All the protein levels were determined by Western blot analysis, and gene expression levels were measured by Real-Time PCR. Our study observed that SAHA treatment decreased cell viability, colony formation and migration in LX2 cells. We found that SAHA increased E-cad expression level, while it decreased N-cad, Vim, COL1A1, COL3A1, alpha-SMA TGF-beta genes expression levels. SAHA decreased the level of E-cad, N-cad, and Vim protein levels. We thought that SAHA possesses potent antifibrotic and anti-EMT properties in LX2

The Effect of EZH2 Inhibition through DZNep on Epithelial-Mesenchymal Transition Mechanism

Although the molecular pathogenesis of hepatocellular carcinoma (HCC) is uncertain, it is known that the epithelial-mesenchymal transition (EMT) mechanism and epigenetic changes have an important role. This study was focused on evaluating the relationship of 3-Deazaneplanocin A (DZNep) with the EMT mechanism, which is a histone methyltransferase inhibitor on HCC and is also known as an enhancer of zeste homolog 2 (EZH2) inhibitor. Cell viability of HepG2 cells (HCC cell line) assessed for DZNep over 72 hours with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Additionally, colony-forming assay, apoptosis assay, RNA isolation, cDNA synthesis, and real-time PCR (RT-PCR) were performed to see the effect of DZNep on HepG2 cells. DZNep reduced cell proliferation for 72 hours, also significantly reduced colony formation in addition it increased the total apoptosis. DZNep on EZH2, E-cadherin, N-cadherin, and Vimentin (Vim) gene expressions was given different results by either decreasing or increasing the expressions. In this study, we observed a positive effect of DZNep on apoptosis and TIMP3 expression level and decreased colony formation. However, it gave complicated results with the level of gene expression E-cadherin and TIMP2, increase the level of Vim and MMP2 expression. Therefore, we think that further studies are necessary to clarify the role of DZNep

Silibinin reduces cell proliferation and migration via EMT pathway in TFK-1 cell line

Objectives: Cholangiocarcinoma (CCA) is usually diagnosed at a late stage due to resistance to chemotherapeutic drugs. Epithelial mesenchymal transition (EMT) is a biological process in cancer that allows multiple biochemical changes that enable epithelial cells to acquire a mesenchymal phenotype. In the present study, we focused on the EMT process which is an important in carcinogenesis and metastatic progression, and also investigate the effect of silibinin on cell proliferation, colony formation, migration, apoptosis, cell cycle and EMT.Methods: Cell viability, apoptosis and cell cycle were measured by Muse Cell Analyzer. All the protein levels were determined by ELISA method.Results : We found that silibinin significantly reduced cell proliferation in a dose-dependent manner and the IC50 value was 200 mu M. Silibinin, significantly inhibited colony formation, inhibited cell migration of cancer cells induced total apoptosis due to the induction of early and late apoptosis, arrest cancer cells in the G0/G1 phase of the cell cycle compared to the control group. We found that E-cadherin, N-cadherin, Vimentin and alpha-SMA protein levels were significantly decreased in the silibinin group compared to the control group.Conclusions: Our results showed that silibinin could significantly prevent tumor proliferation, reduce colony formation, prevent migration, increase the arrest of the G0/G1 phase and induce apoptosis progress in human extracellular cholangiocarcinoma cell line. Another important data is that silibinin inhibits EMT in the cholangiocarcinoma cell line (TFK-1). Our study shows significant effects of silibinin in the TFK-1 cell line, which may be exciting to explore its implications in future animal studies

A new marker for lipid peroxidation: Serum paraoxonase activity in non-alcoholic steatohepatitis

Background/aims: Relationship between hepatic antioxidant paraoxonase 1 (PON1) activity, lipid peroxidation and liver injury was investigated in patients with non-alcoholic steatohepatitis. Methods: A total of 23 patients with non-alcoholic steatohepatitis (15 males, 8 females; mean age: 40.30±7.67 yrs) and 23 healthy controls (14 males, 9 females; mean age: 39.70±8.78 yrs) were enrolled in the study. Serum paraoxonase 1 activity and levels of a well-known lipid peroxidation marker, serum malondialdehyde, were determined. Results: Serum paraoxonase 1 activity decreased significantly in non-alcoholic steatohepatitis compared to the control group (p0.05). Conclusions: Increased lipid peroxidation may be either a cause or a result of liver injury in patients with non-alcoholic steatohepatitis. Although serum paraoxonase 1 activity does not reflect the degree of liver damage in non-alcoholic steatohepatitis, reduced paraoxonase 1 activity, especially in the presence of mild disease, could be interpreted as a biochemical marker of the lipid peroxidation