Association of CCL5 rs2107538, and CCL2 rs3760396 Gene Polymorphisms with the Risk of Cardiovascular Disease.

BACKGROUND: Chemokines are proinflammatory cytokines that play key roles in development of cardiovascular diseases (CVD). Chemokine-induced recruitment of peripheral leucocytes to tissues is a crucial step in the CVD progression. CC chemokines ligand 5, 2 (CCL5 and CCL2), have been characterized as emerging inflammatory biomarkers of atherosclerotic CVD. The aim of this study was to find out whether genetic polymorphisms of CCL5 -403 G>A (rs2107538) and CCL2 -927 G>C, (rs3760396) were associated with the risk of CVD. METHODS: In this case-control study, 500 Iranian individuals including 250 CVD patients and 250 healthy subjects as the control group participated in 2017. Genotyping of CCL5 -403 G>A and CCL2 -927 G>C polymorphisms were executed using Tetra-ARMS PCR method. RESULTS: At genotypic level both CCL5 -403 G>A and CCL2 -927 G>C polymorphisms were not associated with the risk of CVD (P>0.05), even after adjustment by age, sex, race, and history of hypertension, DM and smoking. However, the CCL2 -927 C allele was associated with an increased risk of CVD (OR=1.42, P=0.050) with a higher prevalence in CVD patient than in controls (17% vs. 12%). Moreover, the haplotype analysis revealed that CCL5/CCL2 haplotype (G/C) was a risk factor for CVD (OR=2.13, P=0.001), and that carriers of this haplotype were at 2.13-fold higher risk of CVD than subjects with G/G haplotype. CONCLUSION: CCL2 -927 C variant and CCL5/CCL2 haplotype (G/C) were associated with susceptibility to CVD, and were risk factors for CVD in our population but more studies with large sample size are recommended.

Synthesis and evaluation of 99mTc-DOTA-ARA-290 as potential SPECT tracer for targeting cardiac ischemic region.

Objectives: Myocardial infarction caused by ischemia of heart tissue is the main reason for death worldwide; therefore, early detection can reduce mortality and treatment costs. Erythropoietin (EPO) has protection effects on ischemic tissue due to nonhematopoietic peptide (pHBSP; ARA-290) which is derived from the B-subunit of EPO. Materials and Methods: We designed and synthesized a modified DOTA-(Lys-Dabcyl6, Phe7)-ARA-290 using Fmoc solid-phase peptide synthesis strategies. To improve serum stability, Fmoc-Lys-(Dabcyl)-OH as lipophilic amino acid was synthesized along with Fmoc-Phe-OH which then were substituted with Arg6 and Ala7, respectively; they were then investigated for the ability to detect ischemic cardiac imaging. DOTA-(Lys-Dabcyl6,Phe7)-ARA-290 was labeled with technetium 99m, and its radiochemical purity (RCP), stability in the presence of human serum and, specific bind to hypoxic H9c2 cells were evaluated. In vivo studies for biodistribution and SPECT scintigraphy were checked in a normal and cardiac ischemia rat model. Results: Radiolabeling purity was obtained more than 96% by ITLC, and in vitro stability of the radiopeptide up to 6 hr was 85%. The binding of 99mTc-ARA-290 to hypoxic cells was remarkably higher than normoxic cells (3 times higher than normoxic cells at 1 hr). Biodistribution and SPECT imaging on the cardiac ischemic model showed that radiopeptide considerably accumulated in the ischemic region (cardiac ischemic-to-lung rate = 3.65 ID/g % at 0.5 hr). Conclusion: The results of studies, in vitro and in vivo, indicated that 99mTc-DOTA-(Lys-Dabcyl6,Phe7)-ARA-290 could be an appropriate candidate for early diagnosis of cardiac ischemia.

Effects of N-acetylcysteine on Noise Exposure-induced Oxidative Stress and Depressive- and Anxiety-like Behaviors in Adult Male Mice.

INTRODUCTION: Depression and anxiety are the most common psychiatric disorders. These conditions widely occur in industrial societies and severely affect individuals' lives. N-Acetylcysteine (NAC) is a mucolytic compound with antioxidant and anti-inflammatory effects. This study aimed to investigate the potential therapeutic effects of NAC on chronic noise-induced depression- and anxiety-like behaviors in mice. METHODS: Fifty male BALB/c mice were randomly divided into 5 groups, as follows: control, noise90 dB, noise110 dB, noise 90+NAC, and noise 110+NAC groups. Animals in the noise groups were exposed to 90 dB 2 h/day and 110 dB 2 h/day for 30 days. The NAC groups received NAC (325 mg/kg P.O.) 20 min after being exposed to noise. To evaluate depressive- and anxiety-like behaviors, the examined mice were subjected to the Open Field Test (OFT), Sucrose Preference Test (SPT), Tail Suspension Test (TST), and Elevated Plus Maze (EPM) tasks. At the end of the behavioral tests, the study animals were sacrificed. Accordingly, the levels of Malondialdehyde (MDA), Total Antioxidant Capacity (TAC), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) were determined in the Hippocampus (HIP) and the Prefrontal Cortex (PFC). RESULTS: The obtained results suggested that noise exposure would induce anxiety- and depressive-like behaviors, being reversed by NAC administration. Moreover, chronic administration of NAC significantly increased antioxidant enzyme activities and reduced lipid peroxidation (MDA levels) in the PFC and HIP of noise-exposed mice. CONCLUSION: Our findings revealed that administrating NAC would reduce the adverse effects of noise on the brain and would exert anti-depressant and anxiolytic effects.

Application of radiolabeled peptides in tumor imaging and therapy.

Scientists are looking for new therapies to cope with the rise in cancer worldwide. Since cancer cells overexpress peptide receptors and owing to small size, easy uptake by tumor cells, easy preparation, and with no toxicity, the use of radiolabeled peptides with high specificity and affinity for accurate imaging and therapy has attracted much attention. To develop an ideal imaging or treatment radiolabeled peptide, there are some aspects in the components of radiolabeled peptide including radionuclide, peptide, chelator, and spacer that should be considered. Some peptides, including somatostatin, RGD, neurotensin, bombesin, exendin, vasoactive intestinal peptide, and gastrin are currently under (pre)clinical investigations. Today, nanoparticles are suitable tools for targeting peptide for molecular imaging and therapy of tumors with low toxicity. This paper presents some essential aspects in developing a valuable radiolabeled peptide and some radiolabeled peptides with regard to their applications in tumor imaging and therapy in pre-clinical and clinical phases.

Technetium-99 m-PEGylated dendrimer-G2-(Dabcyle-Lys6,Phe7)-pHBSP: A novel Nano-Radiotracer for molecular and early detecting of cardiac ischemic region.

In cardiac ischemic disorder, pyroglutamate helix B surface peptide (pHBSP) which derived from erythropoietin causes to increase cell stability. To improve the serum stability of pHBSP, two lipophilic amino acids Arg6, Ala7 were replaced with Fmoc-(Dabcyle)-Lys-OH and Fmoc-Phe-OH during the peptide synthesis. This peptide was subsequently conjugated to PEGylated dendrimer-G2 and labeled with 99mTcO4- to detect cardiac ischemic region. Radiochemical purity (RCP) of 99mTc-PEGylated dendrimer-G2-(Dabcyle-Lys6,Phe7)-pHBSP was evaluated by ITLC method. In addition, the radiopeptide was investigated for stability in human serum and binding affinity to hypoxic cells in myocardium H9c2 cell lines. Biodistribution and SPECT/CT scintigraphy were assessed in cardiac ischemic rats. Radiochemical yield indicated that the anionic dendrimer has a very high potential to complex formation with 99mTcO-4 (RCP > 94%) which was stable in human serum with RCP 89% up to 6 h. The binding of 99mTc- nanoconjugate to hypoxic cells was significantly more than normoxic cells (3-fold higher compared to normoxic cells at 1 h). In biodistribution studies, erythropoietin receptor-Beta common receptor (EPO-BcR)-positive uptake in the cardiac ischemic region was 3.62 ± 0.44% ID/g 30 min post injection. SPECT imaging showed a prominent uptake of 99mTc-nanoconjugate in EPO-BcR expressing ischemic heart.

Global prevalence of colistin resistance in clinical isolates of Acinetobacter baumannii: A systematic review and meta-analysis.

INTRODUCTION: Acinetobacter baumannii antimicrobial resistance is a public health concern in developing and developed countries, especially in the hospital setting. Understanding the antibiotic resistance profile can help to provide better guidelines for the prescription of appropriate antibiotics, reduction of antibiotic resistance, and introducing new and effective treatment options. METHOD: Using the PRISMA guidelines, databases of PubMed, Embase, and Cochrane Library were searched systematically from January 1, 2000, to January 1, 2018. All statistical analyses were carried out via Comprehensive Meta-Analysis Software Version 2.0 (Biostat, Englewood, NJ). Depending on the heterogeneity test, either random or fix effect models were used for determining the pooled prevalence of drug resistance. RESULT: A total of 150 studies were included from 41 countries of six different WHO regional offices worldwide. The highest and the lowest rate of resistance were observed for cefotaxime (99%, 95% CI: 95-99.9) in Africa and colistin (1.1%, 95% CI: 0.3-4.5) in Western Pacific, respectively. Lebanon (17.5%, 95% CI: 16-19) and China (12%, 95% CI: 3.5-32.5) had the highest and Germany (0.2%, 95% CI: 0-2.5) had the lowest rate of resistance for colistin. CONCLUSION: Our analysis showed that prevalence and rate of increased colistin resistance in South-East Asia and Eastern Mediterranean countries are higher than other regions of the world. Therefore, the establishment of appropriate antibiotic usage guidelines should be essential in these countries.

Global estimate of gastric cancer in Helicobacter pylori-infected population: A systematic review and meta-analysis.

There is information regarding the rates of gastric cancer (GC) in different populations and the important role of Helicobacter pylori in GC development; however, no comprehensive study has yet been performed to investigate the prevalence of GC in H. pylori-infected patients. PubMed, Embase, and Cochrane Library through January 1, 2000 were searched without language restrictions. Quality of included studies was assessed with a critical appraisal checklist recommended by the Joanna Briggs Institute. All of the analyses were conducted using Comprehensive Meta-Analysis Software Version 2.0 and Stata 14.0. Forty-four studies from 17 countries were included. The pooled frequency of GC was 17.4% (95% confidence interval: 16.4-18.5) in H. pylori-infected population. The frequency of GC among H. pylori-infected population varied markedly across countries. The highest rate of GC was observed in H. pylori-infected individuals from Asian countries. The frequency of GC was relatively high in H. pylori-infected population in the world. However, the eradication of H. pylori might be a promising strategy for GC prevention, especially in high-risk populations such as Asian countries.