CCND1 Overexpression in Idiopathic Dilated Cardiomyopathy: A Promising Biomarker?

Cardiomyopathy, a disorder of electrical or heart muscle function, represents a type of cardiac muscle failure and culminates in severe heart conditions. The prevalence of dilated cardiomyopathy (DCM) is higher than that of other types (hypertrophic cardiomyopathy and restrictive cardiomyopathy) and causes many deaths. Idiopathic dilated cardiomyopathy (IDCM) is a type of DCM with an unknown underlying cause. This study aims to analyze the gene network of IDCM patients to identify disease biomarkers. Data were first extracted from the Gene Expression Omnibus (GEO) dataset and normalized based on the RMA algorithm (Bioconductor package), and differentially expressed genes were identified. The gene network was mapped on the STRING website, and the data were transferred to Cytoscape software to determine the top 100 genes. In the following, several genes, including VEGFA, IGF1, APP, STAT1, CCND1, MYH10, and MYH11, were selected for clinical studies. Peripheral blood samples were taken from 14 identified IDCM patients and 14 controls. The RT-PCR results revealed no significant differences in the expression of the genes APP, MYH10, and MYH11 between the two groups. By contrast, the STAT1, IGF1, CCND1, and VEGFA genes were overexpressed in patients more than in controls. The highest expression was found for VEGFA, followed by CCND1 (p < 0.001). Overexpression of these genes may contribute to disease progression in patients with IDCM. However, more patients and genes need to be analyzed in order to achieve more robust results.

Beneficial Effects of Anti-Inflammatory Diet in Modulating Gut Microbiota and Controlling Obesity.

Obesity has consistently been associated with an increased risk of metabolic abnormalities such as diabetes, hyperlipidemia, and cardiovascular diseases, as well as the development of several types of cancer. In recent decades, unfortunately, the rate of overweight/obesity has increased significantly among adults and children. A growing body of evidence shows that there is a relationship between metabolic disorders such as obesity and the composition of the gut microbiota. Additionally, inflammation is considered to be a driving force in the obesity-gut microbiota connection. Therefore, it seems that anti-inflammatory nutrients, foods, and/or diets can play an essential role in the management of obesity by affecting the intestinal flora and controlling inflammatory responses. In this review, we describe the links between the gut microbiota, obesity, and inflammation, and summarize the benefits of anti-inflammatory diets in preventing obesity.

Targeting Protein Kinases and Epigenetic Control as Combinatorial Therapy Options for Advanced Prostate Cancer Treatment.

Prostate cancer (PC), the fifth leading cause of cancer-related mortality worldwide, is known as metastatic bone cancer when it spreads to the bone. Although there is still no effective treatment for advanced/metastatic PC, awareness of the molecular events that contribute to PC progression has opened up opportunities and raised hopes for the development of new treatment strategies. Androgen deprivation and androgen-receptor-targeting therapies are two gold standard treatments for metastatic PC. However, acquired resistance to these treatments is a crucial challenge. Due to the role of protein kinases (PKs) in the growth, proliferation, and metastases of prostatic tumors, combinatorial therapy by PK inhibitors may help pave the way for metastatic PC treatment. Additionally, PC is known to have epigenetic involvement. Thus, understanding epigenetic pathways can help adopt another combinatorial treatment strategy. In this study, we reviewed the PKs that promote PC to advanced stages. We also summarized some PK inhibitors that may be used to treat advanced PC and we discussed the importance of epigenetic control in this cancer. We hope the information presented in this article will contribute to finding an effective treatment for the management of advanced PC.

Hypothesis of using albumin to improve drug efficacy in cancers accompanied by hypoalbuminemia.

A common problem in many cancers is the resistance of some patients to common drugs or relapse. Hypoalbuminemia has been reported in some of resistant cancer patients.This article evaluates the usefulness of albumin in the treatment of drug-resistant cancers with hypoalbuminemia based on available evidences.Rapid metabolism and drug excretion from the body is one of the causes of drug resistance. Albumin is the major plasma protein to which almost all drugs are bound. There is some evidence that increasing drug binding to albumin has beneficial effects on drug efficacy in some cancers and cancer cells. On the other hand, some reports have shown that cancer cells can use albumin as the energy and amino acid source.We have hypothesized that in this particular group of cancers, adding albumin to a treatment regimen could have a beneficial effect on drug efficacy and dosage. In fact, excess albumin can prevent rapid metabolism of drug by increasing the fraction of albumin-bound drug, and can increase drug delivery to cancer cells due to the absorption of drug-albumin complex by cancer cells.

The Effect of Arsenic Trioxide on All-trans Retinoic Acid Binding to Human Serum Albumin.

Tretinoin or All-trans retinoic acid (ATRA) is an efficient medication in leukemia treatment. Arsenic trioxide (ATO) significantly improves the effectiveness of ATRA. In this study, the effect of ATO on ATRA binding to human serum albumin (HSA) was investigated. Fluorescence and UV-Vis spectroscopy and equilibrium dialysis technique were used to determine ATRA binding to HSA in the presence and absence of ATO and of two compounds, warfarin and ibuprofen, specific for binding to HSA sites I and II, respectively ("site markers"). The association constants for ATRA binding and the number of binding sites as well as the thermodynamic parameters of complex formation, were obtained at different temperatures. Fluorescence results showed a static quenching mechanism for ATRA binding to HSA. The calculated thermodynamic parameters revealed that the binding reaction is a spontaneous and exothermic process and also that hydrogen bonds and van der Waals forces have a central role in the binding of ATRA to HSA. Competitive experiments showed that none of markers seriously prevents ATRA binding to HSA. Interestingly, the fluorescence and equilibrium dialysis data showed that ATO increases the binding of ATRA to HSA, and converts the binding mode of ATRA from mainly hydrogen bonding to include hydrophobic interactions as well. These results suggest that ATO can prevent the metabolism of ATRA and keep it in the blood for longer by increasing the binding of ATRA to HSA.

Role of Copper in the Onset of Alzheimer's Disease Compared to Other Metals.

Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by amyloid plaques in patients' brain tissue. The plaques are mainly made of ß-amyloid peptides and trace elements including Zn2+, Cu2+, and Fe2+. Some studies have shown that AD can be considered a type of metal dyshomeostasis. Among metal ions involved in plaques, numerous studies have focused on copper ions, which seem to be one of the main cationic elements in plaque formation. The involvement of copper in AD is controversial, as some studies show a copper deficiency in AD, and consequently a need to enhance copper levels, while other data point to copper overload and therefore a need to reduce copper levels. In this paper, the role of copper ions in AD and some contradictory reports are reviewed and discussed.

Binding properties of adenosine deaminase interacted with theophylline.

Thermodynamic studies were carried out to evaluate the binding of theophylline on adenosine deaminase (ADA) in 50 mM sodium phosphate buffer pH 7.5, at 300 K, using isothermal titration calorimetry (ITC). A simple method for determination of binding isotherm in the drug--ADA interaction was applied using ITC data. ADA has two binding sites for theophylline, which show positive cooperativity in its sites. The intrinsic association equilibrium constants are 6 and 52 mM(-1) in the first and second binding sites, respectively. Hence, occupation of the first site has produced an appreciable enhancement by 8.7 of the binding affinity of the second site. The molar enthalpies of binding are -12.2 and -14.9 kJ/mol in the first and second binding sites, respectively.