Fluorometric detection of phytase enzyme activity and phosphate ion based on gelatin supported silver nanoclusters.

Phytase is the commercial enzyme for bioconversion of phytate substrate to digestible phosphate ions. Recently silver nanoclusters (AgNCs) have received great attention as the optical transducer nanoparticles in biosensors structure. The novel detection platform was developed to detect the phytase enzyme activity and phosphate ions based on fluorescence quenching of AgNCs. The AgNCs were synthesized through gelatin supported reaction and characterized by TEM, FTIR and XRD analysis. The hydrolytic effect of phytase enzyme and subsequent phosphate release led to suppression of AgNCs fluorescence. The linear range was observed for enzyme in the range of 0.5-5 U/mL with the detection limit of 0.2 U/mL. Also, the same fluorescence quenching effect was observed in the presence of phosphate ion in the linear range of 1 to 16 µM with a detection limit of 0.5 µM. The proposed mechanism showed effectiveness of detection strategy for detection of phytase enzyme and phosphate ion.

Emerging roles of CD133 in the treatment of gastric cancer, a novel stem cell biomarker and beyond.

Gastric cancer (GC) is an aggressive disease with one of the highest mortality rates in the world. In the early stage, most patients are asymptomatic and early diagnosis is difficult. Recently, cancer stem cells (CSCs) have been highlighted as crucial emerging factors in the initiation or invasiveness of solid tumors. CD133, a CSC marker, is highly expressed in various tumors including gastric cancer. CD133-positive cells showed elevated malignant biological behaviors and CD133 upregulation is related to chemoresistance, cancer relapse, and poor prognosis. CD133 also plays an important role in the progression of tumors and metastasis. This review summarizes the current knowledge of the role of CD133 expression in GC and aims to contribute at identifying promising new strategies for treatment and management of gastric cancer.

Association of a variant in the tumor necrosis factor alpha gene with risk of cervical cancer.

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine involved in the regulation of the immune system and potentially the progression of cervical neoplastic lesions. In this study, we aimed to explore the possible relationship between polymorphisms of the TNF-α gene and susceptibility to cervical cancer. The relationship between a single nucleotide polymorphism (SNP) in the TNF-α gene (rs1800629) and the risk of cervical cancer was evaluated in a total of 445 subjects with (n = 153), or without (n = 292) cancer. Genotyping was performed using a Taq-Man based real time PCR method. Logistic regression analysis showed that individuals with AG/AA genotypes had an increased risk of cervical cancer compared to those with a GG genotype (OR 3.79, 95% CI 2.4-5.7, < 0.001). Our findings demonstrated that a genetic variant in the TNF-α gene (rs1800629) was associated with increased level and risk of developing cervical cancer, suggesting its potential use as a genetic risk factor for cervical neoplasia.

The therapeutic potential of renin-angiotensin system inhibitors in the treatment of pancreatic cancer.

Pancreatic cancer is among the most lethal malignancies with poor prognosis and patients become chemoresistant to current therapies, supporting further investigations to identify new therapeutic regimens in the treatment of this condition. Preclinical and clinical studies now appear to support the role of the renin-angiotensin system (RAS) in the regulation of tumor growth, angiogenesis, and metastasis in different malignancies including pancreatic cancer. These studies suggest that RAS blockers; Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs); could have anti-carcinogenic effects and improve clinical outcomes in the management of pancreatic cancer. Here we provided an overview of ACE inhibitors and ARBs as a potential therapeutic option in the treatment of pancreatic cancer.

Examining the Frequency of the JAK2 (V617F) Mutation in Patients with Myeloproliferative Diseases in North Eastern Iran and the Effect of Treatment Intervention.

BACKGROUND: Janus kinase 2 (JAK2) is a tyrosine kinase located in the cytoplasm that plays a critical role in the signal transduction of cytokines and growth hormones. The conversion of valine to phenylalanine at the polypeptide position 617 results in the JAK2 (V617F) mutation, which often found in patients with myeloproliferative neoplasms (MPNs). As a result of this mutation, JAK2 is constitutively activated leading to uncontrolled cell growth. The present study aimed to investigate the frequency and relationship of the JAK2 (V617F) mutation in a population of patients with MPNs in Iran. METHODS: A total of 213 patients with myeloproliferative diseases (MPDs), were included in the study. Real-time PCR was used to detect the presence of the JAK2 (V617F) mutation in the genomic DNA isolated from patient peripheral blood samples. RESULTS: Of the 213 patients with MPDs, approximately 60 (28%) patients were positive for the JAK2 (V617F) mutation. Polycythemia Vera (PV, 42.11%) was the most common MPD, followed by Essential Thrombocythemia (ET, 29.82%), Primary Myelofibrosis (MF, 12.28%), and Chronic Myeloid Leukemia (CML, 10.5%). A significant relationship between all types of MPDs and the clinical course (p< 0.05) was observed. The relationship between age and gender among all types of MPD disease was not significant (p> 0.05). CONCLUSION: Of the examined cohort in North Eastern Iran, 28% of the patients with MPNs were found to have the JAK2 (V617F) mutation which determining the presence of the JAK2 (V617F) mutation helps to decide the correct form of treatment.

Design, synthesis, and SAR study of isopropoxy allylbenzene derivatives as 15-lipoxygenase inhibitors.

OBJECTIVES: Allylbenzenes have been recently developed as inhibitors of lipoxygenases. They decrease peroxidation activity via mimicking 1,4-unsaturated bonds of fatty acids by their allyl portion. We designed and synthesized new derivatives of allyl benzenes (6a-f) with isopropoxy and amide substituents at ortho and meta positions towards allyl group, respectively. The inhibitory potency of the synthetized allylbenzenes against soybean 15-lipoxygenase (SLO) and subsequently structure-activity relationships was assessed. MATERIALS AND METHODS: 3-allyl-4-isopropoxybenzenamine (5) as starting material was synthesized by coupling of 4-nitropheol with allyl bromide, performing Claisen rearrangement and finally reduction of the nitro moiety. Final products 6a-f were prepared via amidation of 5 with the desired acyl chloride. RESULTS: Among the compounds, N-(3-allyl-4-isopropoxyphenyl)adamantan carboxamide (6f) potentially showed best inhibition (IC50 = 1.35 µM) while 6a with cyclopropyl carboxamide moiety was the weakest inhibitor and 6e with phenyl carboxamide moiety showed no effect. Energy minimized 3D structures of the compounds were docked into the active site pocket of SLO. For the aliphatic amides, docking results showed compatibility between inhibitory potency and average Ki of the cluster conformers, in which their allyl moiety oriented towards SLO iron core. For the aliphatic analogs, by enlargement of the amide moiety size the inhibitory potency was increased. CONCLUSION: Docking results showed that orientation of the amide and allyl moieties of the inhibitors in the active site pocket is the major factor in inhibitory potency variation. Based on the mentioned orientation, for cycloaliphatic amides, by enlargement of the amide moiety both inhibition potency and calculated binding energy increases.

Evaluation of the oxidant-antioxidant balance, isoprostane and quantitative CRP in patients with cutaneous leishmaniasis.

INTRODUCTION: Cutaneous leishmaniasis is a dermal disease caused by several species of the genus Leishmania. It is an endemic disease with 1.2 million new cases occurring annually and mostly in developing countries. Oxidative stress is a condition of an imbalance in oxidant/antioxidant which may play a role in many different pathologic conditions. For the first time in this study, we introduced isoprostane as a reliable index for oxidative stress in patients suffering from leishmaniasis. We also investigated the possible relation between quantitative CRP and this disease. METHOD AND MATERIAL: We collected 5 ml blood of 30 patients in addition to the same sample of the control healthy group. After applying appropriate methods, the plasma and serum specimens were extracted in order to conduct oxidant-antioxidant balance and CRP tests in serum as well as measuring isoprostane factor in plasma. STATISTICAL ANALYSIS: We used T-student, ANOVA as well as linear regression to analyze the gathered data with a 0.05 confidence interval in SPSS environment. RESULTS: The results showed a significant difference between the two groups in terms of the oxidant-antioxidant balance. Also, isoprostane and quantitative CRP levels were substantially higher in patients. There was no significant relationship between the mentioned factors and wound size and number. CONCLUSION: Leishmania Amastigotes plays an important role in disturbing the oxidant-antioxidant balance resulting in inflammation and stress in patients. Furthermore, isoprostane was confirmed as a reliable index for evaluating oxidative stress in patients.

Interleukin 10, lipid profile, vitamin D, selenium, metabolic syndrome, and serum antioxidant capacity in elderly people with and without cardiovascular disease: Amirkola health and ageing project cohort-based study.

BACKGROUND: The age-related autoinflammation-mediated atherosclerosis is associated with some immunological, nutritional, and metabolic parameters and redox status. Here, we evaluated the association of circulatory interleukin 10 (IL-10) levels with lipid profile, some nutrients, and total anti-oxidant capacity in elderly people who presented cardiovascular disease (CVD) with or without metabolic syndrome (MetS) and in healthy subjects. METHODS: In this cross-sectional case-control study, 258 sera prepared from elderly people (144 healthy and 114 patient subjects) who participated in a community-based study, the Amirkola Health and Ageing Project (AHAP), were analyzed for IL-10, lipid profile, vitamin D, selenium (Se), antioxidant capacity, and MetS. RESULTS: Compared to patients, the healthy subjects exhibited higher levels of circulatory IL-10 among individuals with detectable serum IL-10 (P = 0.036). However, this difference was not observed when total subjects from both groups were compared, since more than 90% of those people were IL-10-negative. Se, vitamin D, and antioxidant levels were similar in both groups. There was a negative association between IL-10 and body mass index (BMI) (P < 0.050) and an equivocal association with vitamin D levels, whereas the association between IL-10 and other indicated variables was not significant. Significant association was observed between MetS and CVD prevalence (P < 0.001). There was a positive correlation between Se and total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) (P < 0.010) in healthy subjects and with TC in patients (P < 0.050). CONCLUSION: A major proportion of elderly people were serum IL-10-negative, whereas independently to IL-10, MetS was most common in patients with CVD. Weight loss may have the potential to increase IL-10 levels in the elderly.

Effect of propofol and isoflurane on gas exchange parameters following one-lung ventilation in thoracic surgery: a double-blinded randomized controlled clinical trial.

BACKGROUND: The use of anesthetic drugs with minimal inhibitory effects on the hypoxic pulmonary vasoconstriction (HPV) could have a decisive role in preventing the hypoxemia during one-lung ventilation (OLV). OBJECTIVE: The aim of this study was to compare the effects of propofol and isoflurane on the changes in gas exchange parameters following OLV in thoracic surgery. METHODS: This double-blinded randomized controlled clinical trial was conducted on patients who were candidates for elective right thoracotomy referred to the central operating room of Ghaem Hospital in Mashhad, Iran, during February 2016-2017. Patients with age range of 18 to 75 years, class I and II American Society of Anesthesiologists (ASA) and thoracotomy with OLV for pulmonary resection or cyst drainage were included. The patients were randomly allocated (1:1 ratio) into two groups of propofol (P, 50-100µg/kg/min) and isoflurane (I, 1 minimum alveolar concentration (MAC) 1.1%). Partial pressure of carbon dioxide (PaCO2), partial pressure of oxygen (PaO2), end-tidal carbon dioxide (ETCO2) and arterial oxygen saturation (SPO2) were recorded before and 15 minutes after OLV and compared between the two groups. The comparison of the mean gas exchange parameters before and 15 minutes after OLV was performed using Mann-Whitney test in SPSS version 19 software. P<0.05 was considered statistically significant. RESULTS: In this study, 122 patients with mean age of 59.4±14.1 years (two groups of 61) were studied. Both groups were matched for age or gender. The two groups had no significant difference in the gas exchange parameters before the OLV. Only PaCO2 (p=0.001) and ETCO2 (p=0.001) were significantly higher in the propofol group after 15 minutes OLV than in the isoflurane group. However, PaO2 (p=0.67), O2Sat (p=0.333) and PaCO2-ETCO2 gradient (p=0.809) showed no significant difference between the two groups at this minute. CONCLUSION: Based on the results of this study, the propofol or isoflurane selection seems to have no significant effect on the arterial oxygenation. On the other hand, isoflurane and propofol could be an appropriate anesthetic for thoracic surgery by normalizing the carbon dioxide gradient range during the OLV. CLINICAL TRIAL REGISTRATION: The study was also registered at the Iranian Registry of Clinical Trials (IRCT2015123013159N8). FUNDING: The study was financially supported by the Deputy of Research of Mashhad University of Medical Sciences (grant number: 940119).

Therapeutic potency of pharmacological adenosine receptor agonist/antagonist in angiogenesis, current status and perspectives.

OBJECTIVES: Adenosine concentration significantly increases in tumour microenvironment contributing to tumorigenic processes including cell proliferation, survival, invasion and of special interest in this review angiogenesis. KEY FINDINGS: This review summarizes the role of pharmacological adenosine receptor agonist and antagonist in regulating angiogenesis for a better understanding and hence a better management of angiogenesis-associated disorders. SUMMARY: Depending upon the pharmacological characteristics of adenosine receptor subtypes, adenosine elicits anti- or pro-angiogenic responses in stimulated cells. Inhibition of the stimulatory effect of adenosine signalling on angiogenesis using specific pharmacological adenosine receptor agonist, and antagonist is a potentially novel strategy to suppress angiogenesis in tumours.

Saffron against Components of Metabolic Syndrome: Current Status and Prospective.

Saffron, the dried stigmas of Crocus sativus L., is mainly used as a food coloring and flavoring agent. This agricultural product is used in traditional medicine for the treatment of several diseases including asthma, liver disease, menstruation disorders, and, of special interest in this review, metabolic syndrome. Saffron and its active components including crocin, crocetin, and safranal are potential therapeutic candidates for attenuating MetS complications including hypertension, hyperglycemia, obesity, and dyslipidemia. This review summarizes the protective role of saffron and its constituents in the pathogenesis of MetS for a better understanding and hence a better management of this disease.

Matrix Metalloproteinase-13 - A Potential Biomarker for Detection and Prognostic Assessment of Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: Matric metalloproteinase (MMP) 13 gene expression is increased in esophageal squamous cell carcinomas (ESCCs) and associated with increasing tumor invasion, lymph node involvement and decreased survival rates. Levels of the circulating enzyme may be elevated and used as a marker of tumor progression. In this study, clinical application of MMP-13 serum levels was evaluated for early detection, prediction of prognosis and survival time of ESCC patients. MATERIALS AND METHODS: Serum levels of MMP13 were determined by ELISA in 66 ESCC patients prior of any treatment and 54 healthy controls for comparison with clinicopathological data through statistical analysis with Man Whitney U and Log-Rank tests. In addition, clinical value of MMP13 levels for diagnosis was evaluated by receiver operating characteristic (ROC) test. RESULTS: The serum level of MMP-13 in patients (>250 pg/ml) was significantly higher than in the control group (<100 pg/ml) (p value=0.004). Also the results showed a significant correlation between MMP-13 serum levels with tumor stage (p value = 0.003), depth of tumor invasion (p value=0.008), involvement of lymph nodes (p value = 0.011), tumor size (p value = 0.018) and survival time. While there were no significant correlation with grade and location of tumors. ROC analysis showed that MMP-13 level is an accurate diagnostic marker especially to differentiate pre-invasive/ invasive lesions from normal controls (sensitivity and specificity: 100%). CONCLUSIONS: These findings indicate a potential clinical significance of serum MMP13 measurement for early detection and prognostic assessment in ESCC patients.