فهرست مطالب aliasghar rahimian

Negative effects of statins on glucose metabolism have been reported. The present study aimed to investigate the effects of co-administration of vitamin E and atorvastatin on glycemic control in hyperlipidemic patients with type 2 diabetes mellitus (T2DM).

A randomized double-blind clinical trial was conducted at Vali-e-Asr Teaching Hospital (Zanjan, Iran) from July 2017 to March 2018. A total of 30 T2DM female patients were allocated to two groups, namely atorvastatin with placebo (n=15) and atorvastatin with vitamin E (n=15). The patients received daily 20 mg atorvastatin and 400 IU vitamin E or placebo for 12 weeks. Anthropometric and biochemical measures were recorded pre- and post-intervention. Peroxisome proliferator-activated receptor-γ (PPAR-γ) expression was measured in peripheral blood mononuclear cells (PBMCs). Independent sample t test and paired t test were used to analyze between- and within-group variables, respectively. The analysis of covariance (ANCOVA) was used to adjust the effect of baseline variables on the outcomes. P<0.05 was considered statistically significant.

After baseline adjustment, there was a significant improvement in homeostatic model assessment for insulin resistance (HOMA-IR) (P=0.04) and serum insulin (P<0.001) in the atorvastatin with vitamin E group compared to the atorvastatin with the placebo group. In addition, co-administration of vitamin E with atorvastatin significantly upregulated PPAR-γ expression (OR=5.4, P=0.04) in the PBMCs of T2DM patients.

Co-administration of vitamin E and atorvastatin reduced insulin resistance and improved PPAR-γ mRNA expression. Further studies are required to substantiate our findings.

Some heavy metals are nutritionally essential elements playing key roles in different physiological and biological processes, like: iron, cobalt, zinc, copper, chromium, molybdenum, selenium and manganese, while some others are considered as the potentially toxic elements in high amounts or certain chemical forms. Nowadays, various usage of heavy metals in industry, agriculture, medicine and technology has led to a widespread distribution in nature raising concerns about their effects on human health and environment. Metallic ions may interact with cellular components such as DNA and nuclear proteins leading to apoptosis and carcinogenesis arising from DNA damage and structural changes. As a result, exposure to heavy metals through ingestion, inhalation and dermal contact causes several health problems such as, cardiovascular diseases, neurological and neurobehavioral abnormalities, diabetes, blood abnormalities and various types of cancer. Due to extensive damage caused by heavy metal poisoning on various organs of the body, the investigation and identification of therapeutic methods for poisoning with heavy metals is very important. The most common method for the removal of heavy metals from the body is administration of chemical chelators. Recently, medicinal herbs have attracted the attention of researchers as the potential treatments for the heavy metals poisoning because of their fewer side effects. In the present study, we review the potential of medicinal herbs such as: Allium sativum (garlic), Silybum marianum (milk thistle), Coriandrum sativum (cilantro), Ginkgo biloba (gingko), Curcuma longa (turmeric), phytochelatins, triphala, herbal fibers and Chlorophyta (green algae) to treat heavy metal poisoning.

Chanarin-Dorfman syndrome (CDS) is a rare autosomal recessive metabolic disorder caused by mutations in gene encoding the domain-5 of α/β-hydrolase enzyme (ABHD5). It is known as a natural lipid storage disorder arising from impaired lipid metabolism often characterized by hepatomegaly, myopathy, ataxia, non-bullous ichthyosiform erythroderma, hearing loss, and mental retardation. In the present study, we report two affected 28-month-old monozygotic twin boys as new cases of CDS. Genetic analysis was performed in patients, and the results showed a homozygote deletion in exon 4 of ABHD5. According to the the American College of Medical Genetics and Genomics, this variant is categorized as a pathogenic variant.

Fatty acid synthase (FASN) is a key enzyme in de novo lipogenesis pathway. FASN overexpression is a common feature of many human cancers like breast cancer. Furthermore, FASN expression in HER2 - positive cell lines like SKBR3 is more than other cell lines, such as MCF - 7, which are not HER2 - positive. Cichorium intybus is a medicinal herb and methanolic extract of this plant significantly suppressed cell viability and growth in some cancer cells.
In this study, we aimed at investigating the effect of methanolic extract of Cichorium intybus on the FASN expression and, therefore, lipogenesis pathway in human breast cancer SKBR3 cell line.
We assessed the cytotoxicity effect of Chicorium intybus on the cell viability of SKBR3 cells, using MTT assay. In addition, apoptosis rate was assessed by annexinV/PI flow cytometry. Finally, Real time q - PCR was used for the analysis of FASN gene expression.
The results showed that the methanolic extract of Cichorium intybus caused a dose - dependent decrease in the cell viability of SKBR3 cells. Additionally, the treatment of confluent SKBR3 cells with extract led to reduced FASN expression at mRNA level.
These results suggest that Chicorium intybus not only inhibits cell viability in a dose - dependent manner, but also presumably inhibits lipogenesis by markedly decreased FASN expression as a key lipogenic enzyme.

The Basal-Like breast cancer, is always known for lack of expression of estrogen receptor (ER), progesterone receptor (PR) and as well, absence of epidermal growth factor receptor 2 (HER2) gene amplification. Improper expression pattern of ER, PR, and Her2, makes Basal-Like breast tumors resistant to the current hormonal and anti HER2 treatments. In recent decades, several studies have been conducted to investigate the regulatory role of chemical modifications of core histones in gene expression. Their results have shown that histone acetylation is involved in regulation of cell survival. Acetylation of core histones is regulated by the epigenetic-modifying enzymes named Histone Deacetylases (HDACs). As a new approach to control the viability of breast tumor cells resistant to the hormonal and anti-HER2 treatments, we have targeted the HDACs. Using Trichostatin A (TSA) as a known HDACs inhibitor, we have tried to hyperacetylate the core histones of MDA-MB-231 cells as an in vitro model of Basal-Like breast tumors. Then we have investigated the effect of histone hyperacetylation on viability of MDA-MB-231 cells.

MDA-MB-231 cells were cultured in RPMI 1640 medium containing 10% fetal bovine serum (FBS) and were incubated at 37°C, in a humidified incubator with 5% CO2 atmosphere. Then cells were treated with different concentrations of TSA including: 50, 100, 200, 400, 800 and 1000 nM or control (1% DMSO). After 24 and 48 hours, viability of cells was evaluated by MTT assay.

After 24 and 48h exposure to different concentrations of TSA, MDA-MB-231 cells showed a maximum tolerable dose. At higher concentrations, TSA decreased the percentage of cell viability through a time-dose dependent manner. IC50 value for 48h treatment was 600 nM.

Our results indicate that HDACs inhibition and subsequently hyperacetylation of histones, leads to cytotoxic effects on breast tumor cells resistant to the current treatments. Following this pilot research we are trying to suggest molecular mechanisms underlying the anti-proliferative effects triggered by HDACs inhibition.