International Journal of Molecular and Cellular Medicine
Year:2018 | Volume:7 | Issue:1|Papers Count:7

Animal cells possess thousands of long non-coding (lnc) RNAs, such as antisense noncoding RNA in the INK4 locus (ANRIL), which have regulatory roles in the cells’ molecular mechanisms, including X-chromosome inactivation, and developmental processes. These lnc RNAs are known to influence the extensive spectrum of agerelated disorders. Accordingly, there is evidence for the role of these lnc RNAs in cardiovascular diseases, particularly coronary artery diseases (CAD). The aim of this study was to assess whether the expression of the lnc RNAANRIL was associated with a susceptibility to CAD by evaluating the expression level of the two transcripts of ANRIL. Peripheral blood was taken from fifty patients affected by CAD and relative expression of ANRIL was determined by Real-Time PCR assay. The obtained data indicated that theEU741058 transcript expression level significantly decreased in CAD patients in comparison with the healthy individuals (P=0.001). Furthermore, there was no significant association between theNR_003529 transcript expression, and CAD risk in Iranian patients (P=0.751). Our results suggest that the expression level of theEU741058 transcript of ANRIL may be implicated in CAD development, creating a predictive biomarker for CAD patients in future.

Upregulation of matrix metalloproteinases (MMPs), in particularMMP-2 and MMP-9 contributes to secondary pathogenesis of spinal cord injury (SCI) via promoting inflammation. Recently, we have reported that trehalose suppresses inflammatory responses following SCI. Therefore, we investigated the effect of trehalose onMMP-2 and MMP-9expression in SCI. A weight-drop contusion SCI was induced in male rats. Then, the animals received trehalose at three doses of 10 (T10), 100 (T100) and 1000 (T1000) mM intrathecally.MMP-2 and MMP-9 transcripts were then measured in damaged spinal cord at 1, 3 and 7 days after trauma, and compared with vehicle and sham groups. Additionally, behavioral analysis was conducted for 1 week using Basso-Beattie-Bresnahan (BBB) locomotor rating scale. Our data showed an early upregulation ofMMP-9 at 1 day post-SCI. However, MMP-2expression was increased at 3 days after trauma. Treatment with 10 mM trehalose significantly reduced MMP-2expression in 3 and 7 days (P<0.01) and MMP-9 expression in 1, 3, and 7 days (P<0.05) post-damage compared with vehicle. Nonetheless, downregulation of both MMPs was not observed in T100 and T1000 groups. In addition, T10 group showed more rapid recovery of hind limb strength compared with T100 and T1000 groups. We propose that the neuroprotective effect of low dose trehalose is mediated by attenuation ofMMP-2 and MMP-9 expression.

Waardenburg syndrome (WS) is a neurocristopathy with an autosomal dominant mode of inheritance, and considerable clinical and genetic heterogeneity. WS type II is the most common type of WS in many populations presenting with sensorineural hearing impairment, heterochromia iridis, hypoplastic blue eye, and pigmentary abnormalities of the hair and skin. To date, mutations ofMITF, SOX10, and SNAI2 have been implicated in the pathogenesis of WS2. Although different pathogenic mutations have been reported in many ethnic groups, the data on Iranian WS2 patients is insufficient.31WS2 patients, including 22 men and 9 women from 14 families were included. Waardenburg consortium guidelines were employed for WS2 diagnosis. WS2 patients underwent screening forMITF, SOX10, and SNAI2 mutations using direct sequencing and MLPA analysis. Clinical evaluation revealed prominent phenotypic variability in Iranian WS2 patients. Sensorineural hearing impairment and heterochromia iridis were the most common features (67% and 45%, respectively), whereas anosmia was the least frequent phenotype. Molecular analysis revealed ade novo heterozygous c.640C>T (p.R214X) in MITF and a de novoheterozygous SOX10 gross deletion in the study population. Our data help illuminate the phenotypic and genotypic spectrum of WS2 in an Iranian series of patients, and could have implications for the genetic counseling of WS in Iran.

Dysregulated expression of miRNAs can play a vital role in pathogenesis of leukemia. The shortened telomere length, and elevated telomerase activity in acute promyelocytic leukemia cells are mainly indicative of extensive proliferative activity. This study aimed to investigate the effect of overexpression of miR-138 on telomerase activity, and cell proliferation of acute promyelocytic leukemia NB4 cells. MiR-138 was overexpressed in NB4 cells using GFP hsa-miR-138-expressing lentiviruses. hTERT mRNA and protein expression levels were assessed by qRT-PCR and western blot analysis. For evaluation of apoptosis, annexin-V staining and activation of caspases were assessed using flow cytometry and western blot analysis, respectively. Our data demonstrate that overexpression of miR-138 attenuated the hTERT mRNA and protein expression levels. In addition, cell growth was inhibited, and malignant cells underwent caspase mediated-apoptosis in response to miR-138 overexpression. These findings suggest that loss of miR-138 expression may be associated with increased telomerase activity in NB4 cells.Therefore, strategies for up-regulation of miR-138 may result in inhibition of malignant cell growth, and provide a promising therapeutic approach for acute promyelocytic leukemia.

Epidemiological situation of infantile visceral leishmaniasis (IVL), which is a public health problem in Algeria, is almost unknown in the cities of Western part of the country. The aim of this study was to analyze the epidemiological, clinical, biological, therapeutic, and evolutionary aspects of IVL in Western Algeria, to evaluate the performance of the immunochromatography as a rapid diagnostic test of the disease, and to propose a diagnosis approach by real-time polymerase chain reaction (RT-PCR) assay from the serum. This prospective study was performed on 63 suspicious cases of visceral leishmaniasis collected from the infectious diseases department at the Pediatric Hospital of Oran from January 2012 to July 2017. For each patient, the epidemiological parameters, and the clinical and biological data were collected. Bone marrow and blood samples were drawn from all cases. Bone marrow was performed to research amastigote forms ofLeishmania and to identify the species by PCR-sequencing.Blood samples were used to detect anti-Leishmania antibodies as well as parasite DNA. Patients from the Western regions were mostly from rural areas. Sensitivity of RT-PCR from the bone marrow and from serum was 95.45% and 94.44%, respectively. The immunochromatography allowed the disease’s diagnosis for 11 cases whose myelogram did not confirm the presence of the amastigote forms ofLeishmania. Immunochromatography was revealed to be a good technique for disease diagnosis regarding the strongly evocative clinical signs. The results also suggest the interest of the RT-PCR assay from patient serum as a non-invasive sample, in the detection of parasite DNA.

Considering antimicrobial resistance problem, marine microorganisms with the bioactivity against multi-drug resistant (MDR) pathogens have attracted many scientific interests. To address this issue, a total of 21 marine actinomycetes isolated from the Caspian Sea have been screened out. Primary screening via cross-streak method revealed that 3 strains: MN2, MN39, and MN40 produce antimicrobial agents with wide spectrum activity. In the second step, the potent strains were characterized morphologically, and then identified genetically using 16S rRNA analysis. After that, the bioactivity of the ethyl acetate extracts of liquid culture against some MDR bacteria has been studied using disc diffusion method. Finally, the exoenzymatic activity of the strains, and the anti-vibrio activity of the extracts have been evaluated. The nucleotide sequence of the 16S rRNA gene (1.5 kb) showed that the potent strains belong to the genusStreptomyces. The results of disk diffusion method indicated that among the 3 potent isolates, MN39 and MN2 produce biomolecules with antibacterial activity against MDR bacteria specially methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). In addition, potent strains showed remarkable anti-vibrio activity as well as extracellular enzyme production including amylase and protease. The results of this study revealed that the marine actinomycetes isolated from the sediments of Caspian Sea produce biomolecules effective against MDR bacteria, and suggested that these strains deserve to be studied as potential probiotics due to their anti-vibrio activity besides exoenzyme production.

Neisseria meningitidisis a facultative pathogen bacterium which is well founded with a number of adhesion molecules to facilitate its colonization in human nasopharynx track.Neisseria meningitidis is a major cause of mortality from severe meningococcal disease and septicemia.Neisseria meningitidis adhesion, NadA, is a trimeric autotransporter adhesion molecule which is involved in cell adhesion, invasion, and antibody induction. It is identified in approximately 50% ofN. meningitidis isolates, and is established as a vaccine candidate due to its antigenic effects. In the present study, we exploited bioinformatics tools to better understand and determine the 3D structure of NadA and its functional residues to select B cell epitopes, and provide information for elucidating the biological function and vaccine efficacy of Nad A. Therefore, this study provided essential data to close gaps existing in biological areas. The most appropriate model of NadA was designed by SWISS MODEL software and important residues were determined using the subsequent epitope mapping procedures. Locations of important linear and conformational epitopes were determined and conserved residues were identified to broaden our knowledge of efficient vaccine design to reduce meningococcal infectioun in population. These data now provide a theme to design more broadly cross-protective antigens.