Carbohydrate and lipid metabolism in multiple sclerosis: Clinical implications for etiology, pathogenesis, diagnosis, prognosis, and therapy.

Multiple sclerosis (MS) is a complicated autoimmune disease characterized by inflammatory and demyelinating events in the central nervous system. The exact etiology and pathogenesis of MS have not been elucidated. However, a set of metabolic changes and their effects on immune cells and neural functions have been explained. This review highlights the contribution of carbohydrates and lipids metabolism to the etiology and pathogenesis of MS. Then, we have proposed a hypothetical relationship between such metabolic changes and the immune system in patients with MS. Finally, the potential clinical implications of these metabolic changes in diagnosis, prognosis, and discovering therapeutic targets have been discussed. It is concluded that research on the pathophysiological alterations of carbohydrate and lipid metabolism may be a potential strategy for paving the way toward MS treatment.

Serum cytokines, adipokines and ferritin for non-invasive assessment of liver fibrosis in chronic liver disease: a systematic review.

Chronic liver disease (CLD) is a major health problem worldwide. Non-alcoholic fatty liver disease (NAFLD), chronic hepatitis C (CHC), chronic hepatitis B (CHB), and alcoholic liver disease (ALD) are the most common etiologies of CLD. Liver biopsy is the gold standard for assessment of liver fibrosis, however, it is an invasive method. This review attempts to evaluate the usefulness of serum adiponectin, serum leptin, serum ferritin, serum transforming growth factor-ß1 (TGF-ß1), and serum platelet derived growth factor-BB (PDGF-BB) as non-invasive markers in the diagnosis of liver fibrosis/cirrhosis. A systematic search in MEDLINE, Web of Science, Scopus, and local databases was performed to identify articles published in English or Persian as of November 2017. Studies conducted among CLD patients, with biopsy proven fibrosis/cirrhosis, and providing sufficient details of patients' clinicopathological characteristics were included. In the 95 studies included, there were a total of 15,548 CLD patients. More than 83% of studies were carried out in Asia and Europe. The relationship between liver fibrosis/cirrhosis and serum levels of ferritin, adiponectin, leptin, TGF-ß1, and PDGF-BB was assessed in 42, 33, 27, nine, and three studies, respectively. Serum levels of the markers, particularly ferritin, could successfully predict liver fibrosis/cirrhosis, however, these data might not be clinically replicated and further studies are needed.

Prognostic value of rare and complex mutations in EGFR and serum levels of soluble EGFR and its ligands in non-small cell lung carcinoma patients.

BACKGROUND: A number of complex and rare mutations in epidermal growth factor receptor (EGFR) gene have been identified and the clinical implication of serum EGFR ligands has also been reported. However, the prognostic significance of these mutations and also the serum EGFR and its ligands in Non-Small Cell Lung Carcinoma (NSCLC) has remained a challenging issue. This study is aimed at finding the prognostic importance of EGFR rare mutations and serum EGFR, amphiregulin (AR), and TGF-α (Transforming Growth Factor-alpha) in NSCLC. MATERIALS AND METHOD: NSCLC patients (n=98) with mean age of 59±10.5 were enrolled (M/F: 75/23). DNA was extracted from formalin fixed paraffin embedded tissues. Exons 19 and 21 were amplified using polymerase chain reaction followed by direct sequencing for identification of mutations. Serum EGFR, AR, and TGF-α were measured by ELISA. RESULTS: EGFR mutation rate in patients was 37% (exon 19 deletions: 72.2%, exon 21 substitutions: 27.8%). The E872K in exon 21 mutation-positive cases was the most frequent rare mutation detected (90%; 9/10 samples). A significant relationship was found between EGFR exon 21mutations and serum EGFR and TGF-α (P<0.05). Increased serum AR (>3pg/ml) and TGF-α (>10.5pg/ml) were associated with shorter overall survival (P<0.05). CONCLUSIONS: The data clearly show that elevation of serum TGF-α and AR are associated with poor prognosis of NSCLC. In addition to the close relationship between EGFR mutations and serum EGFR, serum TGF-α changes was associated with the gene mutations. These findings could be implicated in clinical decision making related to EGFR-TKIs.

Pharmacogenomics and targeted therapy of cancer: Focusing on non-small cell lung cancer.

Recent studies have been established high degree of genetic diversity in solid organ tumors among individuals and even between individual tumor cells. This intratumor and intertumor genetic diversity results in a heterogeneous tumor with unique characteristics which potentially allows effective drug therapy. The goal of pharmacogenomics is to elucidate the genetic network(s) that underlie drug efficacy and drug resistance. Advances in targeted and personalized therapy play an increasingly important role in many common cancers, notably lung cancer, due to the high incidence, prevalence, mortality and the greater tendency towards drug resistance seen in these patients. Non-small cell lung cancer (NSCLC) is characterized by mutations in the epidermal growth factor receptor (EGFR) and or downstream kinase pathways. This has led to the development of highly selective monoclonal antibodies and EGFR tyrosine kinase inhibitors (EGFR-TKIs) to prevent cancer initiation, proliferation, differentiation, angiogenesis, survival, and invasion. However, resistance to many of these new treatments is induced and further pharmacogenomic analysis has revealed mutations associated with increased or reduced drug efficacy. Combinations of kinase inhibitors or potentially the targeting of cancer stem cells may further increase the success of pharmacogenomics in treating patients with lung cancer.

Epidemiology of HIV/AIDS in the East Azerbaijan Province, Northwest of Iran.

BACKGROUND: This study was performed in response to the rapid propagation of HIV/AIDS across Iran and its status in this region. Accordingly, an evidence-based program is required to combat this disease. OBJECTIVES: The present study estimated the prevalence of HIV/AIDS in East Azerbaijan (population: 3,724,000). MATERIALS AND METHODS: We created a database of all positive cases from 1987 to 2012. We also analyzed and described the epidemiological status of HIV/AIDS during a 25-year period by using SPSS. RESULTS: In East Azerbaijan, 371 HIV/AIDS cases have been reported, i.e. 1 case per 10,000 population. The vast majority of reported cases (91%, n =338) were men, whereas only 9% (n = 33) were women. The mean age of patients was 30.8 ± 12.3 years. Unsafe drug injection (59%, n = 219) and sexual interaction (13%, n = 48) were the two major modes of HIV transmission. In addition, 7% (n = 25) of patients have been diagnosed with HIV, hepatitis B Virus, and hepatitis C virus simultaneously. Moreover, 60% (n = 205) of men were infected via drug injection, while 82% (n = 27) of women were infected via unprotected sexual interaction (P < 0.001). CONCLUSIONS: The results indicate a rapid increase in the number of HIV/AIDS cases in East Azerbaijan, necessitating immediate attention and strategies to combat the rapid spread of the disease. Development of provincial and national HIV/AIDS strategies demands more accurate and comprehensive HIV/AIDS surveillance.