The role of microRNAs involved in PI3-kinase signaling pathway in colorectal cancer

In recent decades, cancer has been one of the most important concerns of the human community, which affects human life from many different ways, such as breast, lung, colorectal, prostate, and other cancers. Colorectal cancer is one of the most commonly diagnosed cancers in the world that has recently been introduced as the third leading cause of cancer deaths in the world. microRNAs have a very crucial role in tumorgenesis and prevention of cancer, which plays a significant role with influencing various factors through different signaling pathways. Phosphoinositide 3 (PI3)-kinase/AKT is one of the most important signaling pathways involved in the control and growth of tumor in colorectal cancer, through important proteins of this pathway, such as PTEN and AKT, that they can perform specific influence on this process. Our effort in this study is to collect microRNAs that act as tumor suppressors and oncomirs in this cancer through PI3-kinase/AKT signaling pathway.     

The role of microRNAs regulating the expression of matrix metalloproteinases (MMPs) in breast cancer development,progression, and metastasis

MicroRNAs (miRNAs) regulate several biological and physiological processes in mammalian cells, including cellular proliferation, differentiation, apoptosis, and metabolism. Recent studies have confirmed the alteration of them during the cancer development. Matrix metalloproteinases (MMPs), belonging to the large family of proteases, have also been demonstrated to play crucial roles in tissue remodeling, and to support cancer progression and metastasis. There are several known miRNAs which regulate the MMP family and their expression. The expression profiles of miRNAs involved in MMP regulation, change during cancer progression, and metastasis. The present review focuses on important miRNAs capable of targeting MMPs through direct and indirect interactions during the breast cancer development, progression, and metastasis.     

Effects of alpha lipoic acid and its derivative “andrographolid-lipoic acid-1” on ulcerative colitis: A systematic review with meta-analysis of animal studies

We aimed to review and meta-analyze the inflammatory and oxidative factors following alpha lipoic acid (ALA) and its derivative “andrographolid-lipoic acid-1” (AL-1) in ulcerative colitis (UC). ALA plays an important role in scavenging intracellular radicals and inflammatory elements. AL-1 is found in herbal medicines with potent anti-inflammatory properties. Data were collected from the Google Scholar, PubMed, Scopus, Evidence-based medicine/clinical trials, and Cochrane library database until 2017, which finally resulted in 22 animal studies (70 rats and 162 mice). The beneficial effects of ALA or AL-1 on the most important parameters of UC were reviewed; also, studies were considered separately in mice and rats. Administration of ALA and AL-1 significantly reduced the tumor necrosis factor-α level compared with the controls, while data were not noteworthy in the meta-analysis (mean differences = −18.57 [95% CI = −42.65 to 5.51], P = 0.13). In spite of insignificant decrease in meta-analysis outcomes (differences = 6.92 [95% CI = −39.33 to 53.16], P = 0.77), a significant reduction in myeloperoxidase activity was shown following ALA or AL-1 treatment compared with the controls. Despite significant differences in each study, we had to exclude some studies to homogenize data for meta-analyzing as they showed insignificant results. Interleukin 6, cyclooxygenase-2, glutathione, malondialdehyde, superoxide dismutase, histopathological score, macroscopic and microscopic scores, disease activity index, body weight change, and colon length were also reviewed. Most studies have emphasized on significant positive effects of ALA and AL-1. Comprehensive clinical trials are obligatory to determine the precious position of ALA or AL-1 in the management of UC.     

Bis‐ and Tetrakis(carboxylato)platinum(IV) Complexes with Mixed Axial Ligands – Synthesis,Characterization, and Cytotoxicity

A series of twelve novel diamminetetrakis(carboxylato)platinum(IV) and 18 novel bis(carboxylato)dichlorido(ethane‐1,2‐diamine)platinum(IV) complexes with mixed axial carboxylato ligands was synthesized and characterized by multinuclear ¹H‐, ¹³C‐, ¹⁵N‐, and ¹⁹⁵Pt‐NMR spectroscopy. Their cytotoxic potential was evaluated (by MTT assay) against three human cancer cell lines derived from ovarian teratocarcinoma (CH1/PA‐1), lung (A549), and colon carcinoma (SW480). In the cisplatin‐sensitive CH1/PA‐1 cancer cell line, diamminetetrakis(carboxylato)platinum(IV) complexes showed IC₅₀ values in the low micromolar range, whereas, for the most lipophilic compounds of the bis(carboxylato)dichlorido(ethane‐1,2‐diamine)platinum(IV) series, IC₅₀ values in the nanomolar range were found.     

Urinary Biomarkers of Polycyclic Aromatic Hydrocarbons Are Associated with Cardiometabolic Health Risk

Background

Polycyclic aromatic hydrocarbons (PAH) are both man-made and naturally occurring environmental pollutants that may be related to cardiometabolic health risk.

Objective

To determine whether PAH is associated with obesity in the adult population and to examine whether urinary concentrations of PAH metabolites are associated with differences in how obesity relates to 3 or more risk factors for the metabolic syndrome (3RFMetS), type 2 diabetes (T2D), hypertension, and dyslipidemia.

Methods

A total of 4765 adult participants from the 2001–2008 National Health and Nutrition Examination Survey were examined. The association between 8 urinary hydroxylated PAH metabolites, obesity, and health were examined using weighted logistic regressions adjusting for age, sex, ethnicity, PIR, smoking status, and urinary creatinine.

Results

There was a positive dose-dependent association between obesity and 2-phenanthrene quintiles (P trend <0.0001). Contrarily, higher quintiles of 1-naphthalene were associated with lower risk of obesity (P trend = 0.0004). For a given BMI, those in the highest quintile of 2-naphthalene, 2-fluorene, 3-fluorene and 2-phenanthrene had a 66–80% greater likelihood of 3RFMetS (P≤0.05) compared to low levels. Higher quintiles of 1-naphthalene, 2-naphthalene, 2-phenanthrene and 1-pyrene were associated with a 78–124% greater likelihood of T2D (P≤0.05) compared to low levels while high 1-naphthalene, 2-naphthalene, 2-fluorene, 3-fluorene and 2-phenanthrene were associated with a 38–68% greater likelihood of dyslipidemia (P≤0.05) compared to lower levels. Finally, 2-naphthalene and 2-phenanthrene were positively associated with hypertension (P trend = 0.008 and P trend = 0.02 respectively).

Conclusions

PAH is related to obesity and the expression of a number of obesity-related cardiometabolic health risk factors. Future research is needed to bring to light the mechanistic pathways related to these findings.     

Atheroprotective and hepatoprotective effects of trans-chalcone through modification of eNOS/AMPK/KLF-2 pathway and regulation of COX-2, Ang-II,and PDGF mRNA expression in NMRI mice fed HCD

Molecular Biology Reports - The effects of trans-chalcone on atherosclerosis and NAFLD have been investigated. However, the underlying molecular mechanisms of these effects are not completely...     

Simplified method for the collection, storage, and comet assay analysis of DNA damage in whole blood

Single-cell gel electrophoresis (comet assay) is one of the most common methods used to measure oxidatively damaged DNA in peripheral blood mononuclear cells (PBMC), as a biomarker of oxidative stress in vivo. However, storage, extraction, and assay workup of blood samples are associated with a risk of artifactual formation of damage. Previous reports using this approach to study DNA damage in PBMC have, for the most part, required the isolation of PBMC before immediate analysis or freezing in cryopreservative. This is very time-consuming and a significant drain on human resources. Here, we report the successful storage of whole blood in ~ 250 μl volumes, at − 80 °C, without cryopreservative, for up to 1 month without artifactual formation of DNA damage. Furthermore, this blood is amenable for direct use in both the alkaline and the enzyme-modified comet assay, without the need for prior isolation of PBMC. In contrast, storage of larger volumes (e.g., 5 ml) of whole blood leads to an increase in damage with longer term storage even at − 80 °C, unless a cryopreservative is present. Our “small volume” approach may be suitable for archived blood samples, facilitating analysis of biobanks when prior isolation of PBMC has not been performed.     

VEGF gene mRNA expression in patients with coronary artery disease

To assess the expression of vascular endothelium growth factor (VEGF) mRNA in unstimulated peripheral blood mononuclear cells of patients with and without coronary artery disease (CAD). We also studied whether the functional VEGF -2,578C/A polymorphism may influence the level of VEGF mRNA expression in individuals undergoing coronary angiography because chest pain. We assessed 50 consecutive patients with angiographically confirmed CAD (CAD+). Also, 50 consecutive individuals with normal coronary studies were included in the study for comparison. VEGF mRNA expression was examined using quantitative real-time PCR and genotyping for VEGF -2,578C/A was performed using ARMS-PCR technique. VEGF mRNA expression was significantly decreased in CAD+ patients when compared to CAD- individuals (p = 0.01). The frequency of VEGF -2578 allele C and genotype CC was increased in CAD+ patients. In this regard, homozygosity for the CC genotype was more commonly observed in CAD+ (30 %) than in those without CAD disease (18 %). However, the difference was slightly out of the range of significance (p = 0.1). In addition, a trend for reduction in the expression of VEGF mRNA was observed when patients carrying the VEGF -2,578AA genotype were compared with those VEGF -2,578AC heterozygous or those homozygous for the VEGF -2,578CC genotype. VEGF gene expression is decreased in individuals with CAD+ disease. The VEGF -2,578C/A polymorphism may influences the expression of VEGF.