Standardised mortality ratios in people exposed to sulphur mustard during the Iran-Iraq war: a retrospective study with 39-year follow-up.

OBJECTIVES: Sulphur mustard (SM) is a chemical weapon agent that was extensively used by Iraqi troops during the Iran-Iraq war (1980-1988), resulting in exposure among Iranian military personnel and civilians. However, there is limited and conflicting information about the long-term mortality effects of SM exposure. This study aimed to determine the standardised mortality ratios (SMRs) in individuals exposed to SM gas during the Iran-Iraq war. STUDY DESIGN: This was a retrospective follow-up study. METHODS: Data were obtained from the Veterans and Martyr Affair Foundation of Iran (VMAF) regarding all confirmed individuals who were exposed to SM during the Iran-Iraq war (1980-1988) up to 30 March 2019. The mortality rate, cumulative mortality and SMR with 95 % confidence intervals (CIs) were calculated to assess mortality in chemical warfare survivors (CWS), and results were compared with the general Iranian population. Overall survival was analysed using the Kaplan-Meier curve, and the log-rank test was employed to compare survival probability across different categories. RESULTS: Among the 48,067 confirmed CWS, a total of 4358 (9.1 %) individuals had died by the end of the study period (30 March 2019), with a mean age of 55.5 ± 14.4 years at the time of death. Overall, at the 39-year follow-up, the mortality rate due to all causes of death for people who were exposed to SM was lower than the general Iranian population (SMR: 0.70, 95 % CI: 0.68-0.72). However, cause-specific SMR analysis showed that the mortality rate due to liver cancer (SMR: 1.98, 95 % CI: 1.59-2.45), poisonings (SMR: 1.92, 95 % CI: 1.52-2.38), respiratory disorders (SMR: 1.59, 95 % CI: 1.46-1.73) and multiple myeloma (SMR: 1.72, 95 % CI: 1.06-2.62) were approximately twofold higher in CWS than the general population. CONCLUSIONS: This study provides valuable insights into the mortality effects of SM exposure among the Iranian population affected by the Iran-Iraq war. The results emphasise the importance of continued monitoring and support for individuals exposed to SM, particularly in the context of managing and addressing the heightened risks associated with liver cancer, poisonings, respiratory disorders and multiple myeloma. Further research and interventions may be necessary to mitigate these specific health challenges in the affected population.

Antibiotic resistance profiles of Salmonella serotypes isolated from animals in Iran: a meta-analysis.

BACKGROUND: Salmonella infection (salmonellosis) is a zoonotic bacterial disease. Widespread use of antibiotics in livestock and poultry production for different purposes such as treatment and growth promotion has led to the emergence of antibiotic-resistant Salmonella, causing treatment of Salmonella infections more difficult with each passing year. AIMS: To determine the antibiotic resistance prevalence of Salmonella serotypes isolated from animals in different provinces of Iran. METHODS: To find eligible articles, we searched the international and national electronic databases using appropriate keywords in English and Persian. RESULTS: After applying predefined criteria, 54 articles reporting antibiotic resistance profiles of Salmonella serotypes were included. Salmonella isolates were mostly resistant against nalidixic acid (67%), tetracycline (66.9%), and streptomycin (49.6%), followed by trimethoprim/sulfamethoxazole (41.6%) and kanamycin (23.6%). The highest sensitivity was observed against imipenem, meropenem, and cefepime with 1.7%, 1.4%, and 1.9% of all isolates being resistant, respectively. CONCLUSION: Results revealed that the prevalence of resistant isolates to nalidixic acid, tetracycline and streptomycin is high and their use must be restricted. In addition, resistance to other antibiotics such as chloramphenicol, ampicillin, cephalothin, cefixime, and enrofloxacin is at an alarming level that calls for attention in the future infection control and antibiotic stewardship programs.

Ceramides and diabetes mellitus: an update on the potential molecular relationships.

Recent evidence suggests that ceramides can play an important pathophysiological role in the development of diabetes. Ceramides are primarily recognized as lipid bilayer building blocks, but recent work has shown that these endogenous molecules are important intracellular signalling mediators and may exert some diabetogenic effects via molecular pathways involved in insulin resistance, ß-cell apoptosis and inflammation. In the present review, we consider the available evidence on the possible roles of ceramides in diabetes mellitus and introduce eight different molecular mechanisms mediating the diabetogenic action of ceramides, categorized into those predominantly related to insulin resistance vs those mainly implicated in ß-cell dysfunction. Specifically, the mechanistic evidence involves ß-cell apoptosis, pancreatic inflammation, mitochondrial stress, endoplasmic reticulum stress, adipokine release, insulin receptor substrate 1 phosphorylation, oxidative stress and insulin synthesis. Collectively, the evidence suggests that therapeutic agents aimed at reducing ceramide synthesis and lowering circulating levels may be beneficial in the prevention and/or treatment of diabetes and its related complications.

A systematic review and meta-analysis on the epidemiology of antibiotic resistance of Vibrio cholerae in Iran.

BACKGROUND: Cholera, an acute diarrheal disease caused by Vibrio cholerae (V. cholerae), is an endemic disease and a major public health problem in Iran. Antibiotic therapy can decrease duration of the disease, transmission of infection and contamination of the environment. Considering different pattern of V. cholerae antibiotic resistance around the world, the aim of the current systematic review and meta-analysis was to evaluate the prevalence of antibiotic resistance of V. cholerae in Iran. METHODS: A systematic review of the literature was performed using related keywords in the electronic national and international databases including SID, Irandoc, Iran Medex and Magiran as well as PubMed, Scopus, Google Scholar and ISI web of knowledge. Up to July 31, 2018, 27 eligible papers were included in our meta-analysis based on the defined inclusion criteria. RESULTS: V. cholerae O1 was the most prevalent strain isolated in Iran and exhibited a high resistance rate against numerous antibiotics including chloramphenicol (33.6%), oxytetracycline (40.2%), trimethoprim/sulphamethoxazole (86%), tetracycline (34.5%), furazolidone (69.8%), streptomycin (93.8%), polymyxin (80.7%), ampicillin (32.1%), nalidixic acid (88.9%), kanamycin (29%) and amoxicillin (30.5%). CONCLUSIONS: According to the meta-analysis results, antibiotic therapy with ciprofloxacin, doxycycline, erythromycin, gentamicin, azithromycin, cefixime and cefepime could be effective for the treatment of severe cases of cholera in Iran.

ETC-1002 (Bempedoic acid) for the management of hyperlipidemia: from preclinical studies to phase 3 trials.

INTRODUCTION: Tolerability problems in treating hypercholesterolemic patients undergoing statin treatment are of growing concern to physicians and patients, thus underlining the need for an agent with a similar mechanism but minimal side effects. A drug with a somewhat similar mechanism to statins but free of muscular side effects is ETC-1002 (bempedoic acid). It inhibits cholesterol biosynthesis at a step preceding HMG-CoA reductase, i.e. ATP citrate lyase (ACLY). A prodrug, ETC-1002 is converted to the active agent only in liver, not in skeletal muscle, and this may prevent any myotoxic activity. Area covered: The mechanism of ETC-1002 activity is described in detail, considering that ACLY inhibition markedly attenuated atherosclerosis in animal models. Clinical studies are also reported. Expert opinion: Present day LDL-C lowering treatments lead to significant reductions of cardiovascular (CV) events but, at times, the need to interrupt statin treatment appears to be dangerous due to a rapid rise in CV risk. The excellent tolerability of ETC-1002 makes it a useful alternative, either alone or as an adjunct to ezetimibe, for patients with statin intolerance needing to achieve significant CV risk reduction. ETC-1002 is also associated with a marked fall in high-sensitivity C-reactive protein.

Molecular mechanisms involved in the protective actions of Selective Estrogen Receptor Modulators in brain cells.

Synthetic selective modulators of the estrogen receptors (SERMs) have shown to protect neurons and glial cells against toxic insults. Among the most relevant beneficial effects attributed to these compounds are the regulation of inflammation, attenuation of astrogliosis and microglial activation, prevention of excitotoxicity and as a consequence the reduction of neuronal cell death. Under pathological conditions, the mechanism of action of the SERMs involves the activation of estrogen receptors (ERs) and G protein-coupled receptor for estrogens (GRP30). These receptors trigger neuroprotective responses such as increasing the expression of antioxidants and the activation of kinase-mediated survival signaling pathways. Despite the advances in the knowledge of the pathways activated by the SERMs, their mechanism of action is still not entirely clear, and there are several controversies. In this review, we focused on the molecular pathways activated by SERMs in brain cells, mainly astrocytes, as a response to treatment with raloxifene and tamoxifen.

Paraoxonase-1 activity in patients with cancer: A systematic review and meta-analysis.

PURPOSE: Paraoxonase-1 (PON1) is a lipolactonase implicated in the elimination of carcinogenic free radicals and in the scavenging mechanisms to maintain oxidative balance. The objective of the present systematic review and meta-analysis was to evaluate possible alterations in serum PON1 activity in patients with cancer. METHODS: A systematic search of the observational studies in humans published in the last 15 years was performed through Medline databases following the PRISMA and STARLITE statements. Further, a keyword-based computerized search with restrictions on publication date, and a meta-analysis of case-control studies was performed. RESULTS: In total, 23 studies were included most of which reported decreased PON1 activity in patients with cancer. This could indicate impaired defense ability against oxidative stress with potential implications in cell proliferation, promotion of genetic instability, and alterations in cellular sensitivity to chemotherapy. CONCLUSION: This systematic review and meta-analysis confirms a consistent association between cancer and decreased serum PON1 activities. These findings may open fruitful lines of research with clinical relevance, and an understanding of molecular alterations underlying carcinogenesis.

Appropriateness of statin prescription in the elderly.

Statins, the most widely used drugs in the Western world, have become a pivotal component in the primary and secondary prevention of vascular diseases. Although benefits have been well documented in younger-than-75-year-old individuals, the value of statins in people aged >75years and over is controversial. The CTT meta-analysis calculated an absolute risk reduction of 0.6%/year per 38.7mg/dl reduction in LDL-C levels in patients aged >75years, that would translate into a number needed to treat of 167. However, the absolute effect of a 38.7mg/dl cholesterol lowering on the rate of annual ischemic heart disease mortality is 10-fold larger in older vs younger patients. In order to advise physician prescription, three major Guidelines have been published over the last few years, i.e. the AHA/ACC and the NLA in the US, and the ESC/EAS in Europe. Moreover, statin prescription in the elderly should also consider the cardiovascular outcomes of elderly patients reported in classical statin preventive trials which give important clues on adherence and persistence of use, as well as on drug safety. The present review discusses benefits of intensive vs moderate statin therapy, justifications for the use of aggressive lipid management in the very old and the use of statins in frail elderlies. The final decision on the therapeutic strategy with statins in elderlies at higher risk to develop cardiovascular events should be always based on a careful analysis of the patient's general health and on the presence of metabolic abnormalities or drug interactions potentially leading to risk.

Stable and sustained release liposomal formulations of celecoxib: In vitro and in vivo anti-tumor evaluation.

Celecoxib (CLX) is a selective COX-2 inhibitor with anticancer potential in a COX-2 dependent and independent manner. CLX's low water solubility has a dose limiting effect on its utilization in cancer treatment. Here, we developed liposomal drug delivery systems to allow a systemic administration and increase tumor accumulation of CLX based on the enhanced permeability and retention (EPR) mechanism. Nine liposomal formulations has been prepared with different phospholipid compositions; among them three sets of liposomal formulations were selected based on characterization and stability for further studies. Anti-tumor effects of CLX-entrapped liposomal formulations were tested in vitro by cytotoxicity test and in vivo in BALB/c mice bearing C26 colon carcinoma. Biodistribution of liposomal-CLX has been studied by radiolabeling of CLX with I125.The selected formulations had average size of about 100 nm, a narrow monomodal distribution with storage stability of at least one year at 4 °C. The HSPC/DSPG/cholesterol/DSPE-PEG2000/CLX (65/10/10/5/10 M ratio) liposomal formulation had slowest release profile and greatest antitumor effects in vivo. This liposomal I125CLX formulation had a three times more accumulation in tumor site in comparison to the free I125CLX. Liposomal CLX may serve as a safe, slow release and effective anti-tumor agent and merits further investigation.

The Genetic Spectrum of Familial Hypercholesterolemia (FH) in the Iranian Population.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder associated with premature cardiovascular disease (CVD). Mutations in the LDLR, APOB, and PCSK9 genes are known to cause FH. In this study, we analysed the genetic spectrum of the disease in subjects from the Iranian population with a clinical diagnosis of FH. Samples were collected from 16 children and family members from five different cities of Iran. Probands were screened for mutations in the LDLR, APOB, and PCSK9 genes using next generation sequencing, with results confirmed by Sanger sequencing. The likely pathology of identified variants was examined using in silico tools. Of the probands, 14 had a clinical diagnosis of homozygous FH and two of heterozygous FH. No mutations were found in either APOB or PCSK9, but nine probands were homozygous for seven different LDLR mutations, with p.(Trp577Arg) occurring in three and p.Val806Glyfs*11 occurring in two patients. Two mutations were novel: p.(Leu479Gln) and p.(Glu668*). Seven probands with a clinical diagnosis of FH were mutation negative. This pilot study, integrating clinical and molecular-based techniques, begins to elucidate the FH heterogeneity and the mutation spectrum in the Iranian population. Such information is important for future disease management and cost savings.

The most prevalent side effects of pegylated liposomal doxorubicin monotherapy in women with metastatic breast cancer: a systematic review of clinical trials.

Despite benefits of systemic chemotherapy in breast cancer treatment, several patients with early-stage breast cancer will develop metastatic breast cancer (MBC). Doxorubicin is among the most active agents against MBC. However, the use of doxorubicin is related to some life-threatening side effects including cardiotoxicity. Many efforts were made to lessen the side effects of doxorubicin and improve its efficacy. Pegylated liposomal doxorubicin (PLD) is a product claimed to achieve these two objectives because of its different pharmacokinetic profile. The aim of this study was to determine the side-effect profile of PLD in MBC through a systematic review of phase II clinical trials. A literature search in PubMed-MEDLINE was performed using terms covering nano-based pharmaceutical systems, 'breast cancer' and 'doxorubicin'. Articles were evaluated according to the inclusion criteria. Reported hematological and non-hematological side effects were categorized. Out of 718 articles that were initially identified, 8 were in accordance with the inclusion criteria. We found that the most important side effects of PLD were skin toxicity and mucositis, but the proportion of patients who showed grade III and IV of these side effects was relatively low. On the other hand, the occurrence of cardiotoxicity, the most important problem with doxorubicin, was considerably reduced in patients treated with PLD. Although PLD has demonstrated a lower toxicity profile than conventional anthracyclines, it has also new side effects. However, it seems that the reduced cardiotoxicity of PLD has made it a more appropriate option in patients with MBC, especially in those with risk factors for cardiac diseases.

Preventing cardiovascular heart disease: Promising nutraceutical and non-nutraceutical treatments for cholesterol management.

Hypercholesterolemia is one of the major risk factors for the development of cardiovascular disease. Atherosclerosis resulting from hypercholesterolemia causes many serious cardiovascular diseases. Statins are generally accepted as a treatment of choice for lowering low-density lipoprotein (LDL) cholesterol, which reduces coronary heart disease morbidity and mortality. Since statin use can be associated with muscle problems and other adverse symptoms, non-adherence and discontinuation of statin therapy often leads to inadequate control of plasma cholesterol levels and increased cardiovascular risk. Moreover, there is compelling evidence on the presence of still considerable residual cardiovascular risk in statin-treated patients. Ezetimibe improves cholesterol-lowering efficacy and provides mild additional cardiovascular protection when combined with statin treatment. Despite a favorable safety profile compared to statins, ezetimibe-induced cholesterol-lowering is modest when used alone. Hence, there is a critical need to identity additional effective hypolipidemic agents that can be used either in combination with statins, or alone, if statins are not tolerated. Thus, hypolipidemic agents such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, apolipoprotein B-100 antisense oligonucleotides, cholesteryl ester transfer protein (CETP) inhibitors, and microsomal triglyceride transfer protein (MTTP) inhibitors, as well as yeast polysaccharides (beta-glucans and mannans) and compounds derived from natural sources (nutraceuticals) such as glucomannans, plant sterols, berberine, and red yeast rice are being used. In this review, we will discuss hypercholesterolemia, its impact on the development of cardiovascular disease (CVD), and the use of yeast polysaccharides, various nutraceuticals, and several therapeutic agents not derived from 'natural' sources, to treat hypercholesterolemia.

Imaging techniques: new avenues in cancer gene and cell therapy.

Cancer is one of the world's most concerning health problems and poses many challenges in the range of approaches associated with the treatment of cancer. Current understanding of this disease brings to the fore a number of novel therapies that can be useful in the treatment of cancer. Among them, gene and cell therapies have emerged as novel and effective approaches. One of the most important challenges for cancer gene and cell therapies is correct monitoring of the modified genes and cells. In fact, visual tracking of therapeutic cells, immune cells, stem cells and genetic vectors that contain therapeutic genes and the various drugs is important in cancer therapy. Similarly, molecular imaging, such as nanosystems, fluorescence, bioluminescence, positron emission tomography, single photon-emission computed tomography and magnetic resonance imaging, have also been found to be powerful tools in monitoring cancer patients who have received therapeutic cell and gene therapies or drug therapies. In this review, we focus on these therapies and their molecular imaging techniques in treating and monitoring the progress of the therapies on various types of cancer.

Uric acid and bone mineral density in postmenopausal osteoporotic women: the link lies within the fat.

The association between serum uric acid (SUA) levels and bone mineral density (BMD) is controversial. Fat accumulation is linked to SUA and BMD, thus possibly explaining the mixed results. We found that adiposity drives part of the association between SUA and BMD in women with postmenopausal osteoporosis. INTRODUCTION: Both positive and negative associations between SUA and BMD have been reported. SUA levels and BMD increase with higher body weight and other indices of adiposity; hence, the association between SUA and BMD might be a consequence of the confounding effect of adiposity. We investigated in this cross-sectional study whether the association between SUA and BMD is independent of measures of fat accumulation and other potential confounders. METHODS: SUA levels, femur BMD, markers of bone metabolism, body mass index (BMI), fat mass (FM), waist circumference (WC), and abdominal visceral fat area were measured in 180 treatment-naive postmenopausal osteoporotic women (mean age 66.3 ± 8.5 years, age range 48-81 years). RESULTS: Women with higher SUA levels (third tertile) had significantly higher femur BMD and lower cross-linked C-terminal telopeptide of type I collagen (CTX) and bone alkaline phosphatase (bALP) levels. SUA levels were positively associated with all indices of adiposity. In multivariable analysis with femur BMD as dependent variable, the association between logarithmic (LG)-transformed SUA levels and BMD (beta = 0.42, p < 0.001) was lessened progressively by the different indices of adiposity, like LG-BMI (beta = 0.22, p = 0.007), LG-WC (beta = 0.21, p = 0.01), LG-FM (beta = 0.18, p = 0.01), and LG-abdominal visceral fat area (beta = 0.12, p = 0.05). The association between SUA levels and markers of bone metabolism was dependent on the effect of confounders. CONCLUSION: In postmenopausal osteoporotic women, the strong univariable association between SUA levels and femur BMD is partly explained by the confounding effect of indices of adiposity.

Molecular imaging and cancer gene therapy.

Gene therapy is known as one of the most advanced approaches for therapeutic prospects ranging from tackling genetic diseases to combating cancer. In this approach, different viral and nonviral vector systems such as retrovirus, lentivirus, plasmid and transposon have been designed and employed. These vector systems are designed to target different therapeutic genes in various tissues and cells such as tumor cells. Therefore, detection of the vectors containing therapeutic genes and monitoring of response to the treatment are the main issues that are commonly faced by researchers. Imaging techniques have been critical in guiding physicians in the more accurate and precise diagnosis and monitoring of cancer patients in different phases of malignancies. Imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are non-invasive and powerful tools for monitoring of the distribution of transgene expression over time and assessing patients who have received therapeutic genes. Here, we discuss most recent advances in cancer gene therapy and molecular approaches as well as imaging techniques that are utilized to detect cancer gene therapeutics and to monitor the patients' response to these therapies worldwide, particularly in Iranian Academic Medical Centers and Hospitals.Cancer Gene Therapy advance online publication, 18 November 2016; doi:10.1038/cgt.2016.62.

Circulating microRNA-192 as a diagnostic biomarker in human chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is known as the most common lymphoid malignancy in the Western world. MicroRNAs (miRNAs) are a class of small noncoding RNAs with pivotal roles in cellular and molecular processes related to different malignancies including CLL. Recently, some studies have shown that miR-192 plays a key role in CLL pathogenesis through increasing CDKN1A/p21 levels, suppression of Bcl-2 and enhancement of wild-type P53 and cell cycle arrest. Forty samples, including 20 patients with CLL, diagnosed in Omid hospital (Isfahan, Iran) and 20 healthy controls were sampled during a period of 4 months. Using real-time PCR method, expression of miR-192 was analyzed in peripheral blood mononuclear cells (PBMCs) of CLL patients in comparison with healthy subjects. In silico molecular signaling pathway enrichment analysis was also performed on validated and predicted targets (targetome) of miR-192 in DAVID database to explore possible role of miR-192 in some pathways. The expression of miR-192 was found to be significantly reduced (~2.5-folds) in CLL patients compared with healthy subjects (P=0.002). In silico molecular signaling pathway enrichment analysis detected cell indicated signaling pathway as one of the most statistically relevant pathway with miR-192 targetome. Our findings showed that miR-192 could be a biomarker for early diagnosis of CLL.

Adjunctive Therapy with Curcumin for Peptic Ulcer: a Randomized Controlled Trial.

BACKGROUND: Curcumin, the bioactive ingredient of turmeric, has been shown to improve the treatment of peptic ulcer (PU) in animal studies. However, clinical studies confirming this effect of curcumin have been scant. OBJECTIVE: To assess the efficacy of adjunctive therapy with curcumin on the eradication of Helicobacter pylori infection and severity of dyspepsia in patients with PU. METHODS: In this randomized double-blind placebo-controlled parallel-group trial, patients diagnosed with PU were assigned to standard H. pylori eradication triple therapy with clarithromycin (500 mg b.i.d.), amoxicillin (1 000 mg b.i.d.) and pantoprazole (40 mg b.i.d.), and randomized to receive either curcumin (500 mg/day) or placebo as adjunct to standard treatment. Severity of dyspepsia symptoms was evaluated using the Hong Kong dyspepsia index (HKDI). Eradication of H. pylori infection was assessed using the urea breath test (UBT) at 4 weeks following the end of treatment. RESULTS: Adjunctive therapy with curcumin was associated with a greater improvement of dyspepsia symptoms according to the HKDI score (change score: -12.90±2.81 vs. -9.60±3.39 in the curcumin and control group, respectively; p<0.001). The number of subjects whose dyspepsia was resolved during the course of treatment was significantly higher in the curcumin (27.6%) vs. placebo (6.7%) group (p=0.042). Nevertheless, the results of UBT test showed equal rate (73.3%) of H. pylori eradication in the study groups. Curcumin was safe during the course of trial. CONCLUSION: Addition of curcumin on top of the standard anti-helicobacter regimen in patients with PU is safe and improves dyspepsia symptoms but has no enhancing effect on the eradication of H. pylori infection.

Improvement of hypertension, endothelial function and systemic inflammation following short-term supplementation with red beet (Beta vulgaris L.) juice: a randomized crossover pilot study.

Hypertension is a major risk factor for cardiovascular disease and has a prevalence of about one billion people worldwide. It has been shown that adherence to a diet rich in fruits and vegetables helps in decreasing blood pressure (BP). This study aimed to investigate the effect of raw beet juice (RBJ) and cooked beet (CB) on BP of hypertensive subjects. In this randomized crossover study, 24 hypertensive subjects aged 25-68 years old were divided into two groups. One group took RBJ for 2 weeks and the other group took CB. After 2 weeks of treatment, both groups had a washout for 2 weeks then switched to the alternate treatment. Each participant consumed 250 ml day(-1) of RBJ or 250 g day(-1) of CB each for a period of 2 weeks. Body weight, BP, flow-mediated dilation (FMD), lipid profile and inflammatory parameters were measured at baseline and after each period. According to the results, high-sensitivity C-reactive protein (hs-CRP) and tumour necrosis factor alpha (TNF-α) were significantly lower and FMD was significantly higher after treatment with RBJ compared with CB (P<0.05). FMD was significantly (P<0.05) increased, but systolic and diastolic BP, intracellular adhesion molecule-1 (ICAM-1), vascular endothelial adhesion molecule-1 (VCAM-1), hs-CRP, interleukin-6, E-selectin and TNF-α were significantly (P<0.05) decreased with RBJ or CB. Total antioxidant capacity was increased and non-high-density lipoprotein (HDL), low-density lipoprotein (LDL) and total cholesterol (TC) were decreased with RBJ but not with CB. Although both forms of beetroot were effective in improving BP, endothelial function and systemic inflammation, the raw beetroot juice had greater antihypertensive effects. Also more improvement was observed in endothelial function and systemic inflammation with RBJ compared with CB.

PiggyBac as a novel vector in cancer gene therapy: current perspective.

Selection of suitable delivery system is one of the crucial aspects in gene therapy that determines the efficiency of gene therapy. The past two decades have witnessed extensive efforts for finding safe and efficient vectors to overcome the limitations of viral vectors. The utilization of DNA transposon-based vectors for gene therapy has emerged as a promising non-viral alternative. DNA 'cut-and-paste' is one of the main mechanisms of genome engineering by transposon elements. However, the lack of an efficient transposition system has limited the utilization of transposon vectors in mice and mammalian systems. PiggyBac (PB) is known as a highly efficient DNA transposon originally isolated from Trichoplusia ni as an alternative to Sleeping Beauty (SB). It has been shown that PB can be functional in various species including mammalian systems. This vector could overcome some limitations of other vectors in cancer gene therapy. Some advantages of PB include the capacity for integration into the genome and providing a stable expression, capacity to harbor 10 and 9.1 kb of foreign DNA into the host genome, without a significant reduction in their transposition activity and display non-overlapping targeting preferences. However, to advance PB to clinical applications, some obstacles still require to be overcome to improve its safety and efficiency. Hence, it seems that this vector could open new horizons in gene and cancer therapy.

SERUM LEVELS OF FIBROBLAST GROWTH FACTOR 21 IN TYPE 2 DIABETIC PATIENTS.

BACKGROUND AND PURPOSE: Fibroblast growth factor 21 (FGF21) has recently been identified as a metabolic regulator, but its physiological role is still not completely known. The aim of this study was to evaluate serum FGF21 levels in an Iranian population with type 2 diabetes. MATERIALS AND METHODS: This cross-sectional study was conducted in patients with type 2 diabetes. All patients were evaluated for fasting serum levels of glucose, glycated hemoglobin (HbA1c), lipids, urea and creatinine. Participants were divided into two groups with poorly-controlled and well-controlled diabetes based on their HbA1c levels. Healthy non-diabetic subjects (matched with patients in terms of age, sex and body mass index [BMI]) were also recruited as control group. Serum FGF21 concentrations were determined in all subjects using ELISA. RESULTS: Of the evaluated 141 subjects, 49 (34.8%) were categorized as having well-controlled diabetes, 66 (46.8%) had poorly-controlled diabetes, and there were 26 subjects in the normal control group. Mean serum FGF-21 concentration was 337.89±283.67 ng/L in the diabetic group and 237.25±43.22 ng/mL in the non-diabetic group (p<0.001). Mean serum FGF21 level was 237.25 ± 43.22 ng/mL in the control group, 309.81 ± 301.68 ng/mL in the well-controlled diabetic group, and 358.73 ± 269.98 ng/mL in the poorly controlled diabetic group. Serum FGF21 level in the poorly controlled diabetic group was significantly higher than that in the well-controlled diabetic and the healthy control groups (p=0.02) but there was no significant difference between the well-controlled and healthy groups. There was no significant association between serum FGF21 levels with lipid levels, presence of diabetic complications and BMI (p > 0.05). CONCLUSIONS: The present results suggested an association between elevated serum levels of FGF21 and poor control of diabetes. Future studies are warranted to elucidate the prognostic role of these elevated levels of FGF21 in diabetic subjects.