International journal of molecular and cellular medicine

Journal Information
ISSN / EISSN : 2251-9637 / 2251-9645
Current Publisher: Babol University of Medical Sciences (10.22088)
Total articles ≅ 4
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Fereshteh Dorazehi, Mohammad Nabiuni, Hanieh Jalali
International journal of molecular and cellular medicine, Volume 7, pp 91-101; doi:10.22088/IJMCM.BUMS.7.2.91

Abstract:
Scaffolds derived from decellularized tissues provide a natural microenvironment for cell culture. Embryonic cerebrospinal fluid (e-CSF) contains factors which play vital roles in the development of the nervous system. This research was aimed to survey the effect of Wistar rat e-CSF on neural differentiation of bone marrow derived mesenchymal stem cells (BM-MSCs) cultured on the human amniotic membrane (AM). BM-MSCs were collected from femurs and tibias, and were cultured in Dulbecco's Modified Eagle's Medium. The placenta was harvested from healthy women during cesarean section and AM was acellularized using EDTA and physical scrubbing. e- CSF was harvested from rat fetuses at E17. Adequate numbers of BM-MSCs were cultured on acellularized membrane, and were treated with E17 CSF for 7 days. MTT (3-(4, 5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide) assay confirmed the survival and proliferation of BM-MSCs cultured on AM derived scaffold. Hematoxylin/eosin staining and scanning electron microscopy showed the morphological and the structural changes of BM-MSCs throughout the culture and treatment with e-CSF. The results of immunocytochemistry showed that microtubule associated protein 2 and beta-III tubulin were expressed in BM-MSCs cultured on acellular amnion scaffold and treated with e-CSF. Our results showed for the first time that the combination of acellular AM as a natural scaffold and e-CSF as a source of neurological factors could effectively improve the BM-MSCs cultivation and differentiation
Manoj Kumar, Vijay Kumar Shukla, Pravas Kumar Misra, Mercy Jacob Raman
International journal of molecular and cellular medicine, Volume 7, pp 119-132; doi:10.22088/IJMCM.BUMS.7.2.119

Abstract:
Base excision repair (BER) pathway is one of the repair systems that has an impact on radiotherapy and chemotherapy for cancer patients. The molecular pathogenesis of gallbladder cancer is not known extensively. In the present study we investigated whether the expression of AP endonuclease 1 (APE1) and DNA polymerase β (DNA pol β), key enzymes of BER pathway has any clinical significance with gallbladder carcinogenesis. 41 gallbladder cancer, 27 chronic cholecystitis, and 3 normal gallbladder specimens were analyzed for the expression of APE1 and DNA polymerase β by western blotting, and subcellular localization studied by immunohistochemistry. The enzymatic activity of APE1 was also studied. The correlations with expression of the above proteins with clinical-pathological characteristics of gallbladder cancer patients were analyzed. The integrated density value ratio (relative expression) of total APE1 (37 kDa + 35 kDa variant) analyzed in the three groups of tissues, was 0.76±0.03 in normal gallbladder, 0.91±0.08 in chronic cholecystitis, and 1.12±0.05 in gallbladder cancer. APE1 was found to be up-regulated in 80% of gallbladder carcinoma samples (P = 0.01). A positive trend of APE1 expression with tumor stage and lymph node positivity was observed. The enzymatic activity of APE1 was found higher in gallbladder cancer samples in comparison with chronic cholecystitis. The integrated density value ratio of DNA polymerase β for normal gallbladder, chronic cholecystitis and gallbladder cancer tissue samples were 0.46±0.03, 0.7±0.06 and 1.33±0.1, respectively. DNA polymerase β was found to be upregulated in almost all gallbladder carcinoma samples (P =0.0001), and its expression was negatively correlated with age (P=0.02). DNA polymerase β expression showed a positive trend with tumor stage and nuclear differentiation of gallbladder cancer. It may be concluded that alteration of these BER pathway proteins may be the causal factors for carcinogenesis of gallbladder, and has targeted therapeutic potential.
Puneet Gandhi, Richa Khare, Hanni VasudevGulwani, Sukhpreet Kaur
International journal of molecular and cellular medicine, Volume 7, pp 111-118; doi:10.22088/IJMCM.BUMS.7.2.111

Abstract:
In addition to histopathological parameters, evaluation of associated hematological factors is essential for devising a sensitive prognostic scale in glioma. Increased neutrophil-lymphocyte ratio (NLR), a marker of systemic inflammatory response, has recently been associated with worse outcome in various cancers. Given that glioma progression is characterized by inflammation, aggressive angiogenesis, and invasion, increased levels of systemic human-chitinase-3-like-one protein (YKL-40) have also been linked to poor prognosis. The aim of the present study was to assess the plausible association of YKL-40, NLR, and platelet count with increasing tumor grade, and evaluate their status as independent prognostic factors in terms of overall survival (OS) in treatment naive patients with diffuse glioma. Plasma levels of both biochemical markers in 72 diffuse gliomas, median age 42 years, were compared with 36 controls. Comparison of YKL-40, NLR, and PC with respect to tumor grade was found to be significant for each of the markers (P
Renata Neves Granito, Ana Claudia Muniz Renno, Hirochi Yamamura, Matheus Cruz De Almeida, Pedro Luiz Menin Ruiz, Daniel Araki Ribeiro
International journal of molecular and cellular medicine, Volume 7, pp 80-90; doi:10.22088/IJMCM.BUMS.7.2.80

Abstract:
Natural or synthetic hydroxyapatite (HA) has been frequently used as implant materials for orthopaedic and dental applications, showing excellent bioactivity, adequate mechanical rigidity and structure, osteoconductivity and angiogenic properties, no toxicity, and absence of inflammatory or antigenic reactions. HA can be easily synthesized or extracted from natural sources, such as bovine bone. However, the manufacturing costs to obtain HA are high, restricting the therapy. Herein, much effort has been paid for obtaning alternative natural sources for HA. The potential of HA extracted from skeleton of animals has been investigated. The aim of this review is to exploit the potential of HA derived from fish to fulfill biological activities for bone tissue engineering. In particular, HA from fish is easy to be manufactured regarding the majority of protocols that are based on the calcination method. Furthermore, the composition and structure of HA from fish were evaluated; the biomaterial showed good biocompatibility as a result of non-cytotoxicity and handling properties, demonstrating advantages in comparison with synthetic ones. Interestingly, another huge benefit brought by HA from bone fish is its positive effect for environment since this technique considerably reduces waste. Certainly, the process of transforming fish into HA is an environmentally friendly process and stands as a good chance for reducing costs of treatment in bone repair or replacement with little impact into the environment.
Raheleh Rafaiee, Naghmeh Ahmadiankia
International journal of molecular and cellular medicine, Volume 7, pp 69-79; doi:10.22088/IJMCM.BUMS.7.2.69

Abstract:
The brain is an important organ that controls all sensory and motor actions, memory, and emotions. Each anatomical and physiological modulation in various brain centers, results in psychological, behavioral, and sensory-motor changes. Alcohol and addictive drugs such as opioids and amphetamines have been shown to exert a great impact on brain, specifically on the hippocampus. Emerging evidence has indicated that altered hippocampal neurogenesis is associated with the pathophysiology of neuropsychological disorders including addiction. The addictive drugs impair neurogenesis and undermine the function of neural stem/progenitor cells in hippocampus. This feature was claimed to be one of the underlying mechanisms of behavioral changes in patients with addiction. As the impairment of stem cells’ function has been proven to be the underlying cause of pathologic neuroadaptations in the brain, the administration of stem cell populations has shown promising results for re-modulating of neuronal status in the brain and especially in the hippocampus. Among the different types of stem cells, bone marrow derived mesenchymal stem cells are the most proper candidates for stem cell therapies. In this review article, the recent studies on the effects of addictive drugs on brain neurogenesis, and also the promising potential effects of stem cells in curing addiction related hippocampal damages are discussed.
Ahmed Nafis, Najoua Elhidar, Brahim Oubaha, Salah Eddine Samri, Timo Niedermeyer, Yedir Ouhdouch, Lahcen Hassani, Mustapha Barakate
International journal of molecular and cellular medicine, Volume 7, pp 133-145; doi:10.22088/IJMCM.BUMS.7.2.133

Abstract:
Fungal diseases are currently a serious public health problem, due to the limited number of fact-based effective principles, and the emergence of resistant strains to the polyenic antifungals. The aim of this study was to screen, for non-polyenic antifungals production by Actinobacteria, and to validate the screening program by characterizingthe produced compounds.Actinobacteria isolates were tested against four clinic human-pathogenic fungi isolated from Hospital Mohammed V Rabat, Morocco. The production of non-polyenic antifungal metabolites by active isolates was investigated based on the yeast cell specificity as challenging targets, antibacterial activity, activity against resistant Candida tropicalis R2 and Pythium irregular (resistant to polyenes), inhibition of antifungal activity by the addition of exogenous ergosterol, and the UV-visible light spectrophotometric analysis of the active crude extracts.The antifungal compound produced was purified using various chromatographic techniques and the selected producing strain was identified using the polyphasic approach.Among 480 Actinobacteria isolates, 55 showed antifungal activity against all tested clinically derived fungi. After performing the screening program, 4 Actinobacteria that hadall the desired criteriawere selected. Using the polyphasic approach, the taxonomic position of the selected Streptomyces AS25, isolated from rhizospheric soil of Alyssum spinosum, showed that it belongs to Streptomyces genus with 100% partial 16S similarity with Streptomyces albidoflavus NBRC13010. On the basis of HPLC and mass spectrometry, the purified compound produced by Streptomyces AS25 was identified as a non-polyenic lactone, antimycin A19, which has been found for the first time to be produced by Streptomyces albidoflavus strain. Following the obtained results, it is important to note that our screening criteria for non-polyenic antifungals have been validated and the rhizospheric soil represents an interesting source to isolate Actinobacteria.
Jalal Gharesouran, Mohammad Taheri, Arezou Sayad, Soudeh Ghafouri-Fard, Mehrdokht Mazdeh, Mir Davood Omrani
International journal of molecular and cellular medicine, Volume 7, pp 102-110; doi:10.22088/IJMCM.BUMS.7.2.102

Abstract:
Recent studies have revealed that long noncoding RNAs (lncRNAs) are connected with pathogenesis of neurodegenerative diseases. Additionally, glucocorticoids have fundamental regulatory roles on the immune system, and act as potent therapeutic compounds for autoimmune and inflammatory diseases. The long noncoding RNA growth arrest-specific 5 (GAS5) which accumulates inside the cells in response to cellular starvation/growth arrest, acts as a potent repressor of the glucocorticoid receptor (GR) through its glucocorticoid response element (GRE). The aim of the present study was to investigate the role of lncRNA GAS5 and its downstream target Nuclear Receptor Subfamily 3 Group C Member 1(NR3C1) in the pathogenesis of multiple sclerosis (MS), and to define the role of GAS5 in the regulation of NR3C1 expression. Quantitative polymerase chain reaction was performed for investigating the expression of GAS5 and NR3C1 in MS patients and healthy subjects. We found that GAS5 levels were up-regulated in the MS patients, blood compared with healthy subjects in correlation with NR3C1 expression. Our findings suggest that GAS5 may play on important role in the molecular etiology and treatment of MS.
Hamed Norouzi, Abolghasem Danesh, Mojtaba Mohseni, Mohammad Rabbani Khorasgani
International journal of molecular and cellular medicine, Volume 7, pp 44-52; doi:10.22088/IJMCM.BUMS.7.1.44

Abstract:
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 genus Streptomyces. 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.
Rima Manafi Shabestari, Fatemeh Alikarami, Davood Bashash, Mostafa Paridar, Majid Safa
International journal of molecular and cellular medicine, Volume 7, pp 24-31; doi:10.22088/IJMCM.BUMS.7.1.24

Abstract:
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.
Nazanin Jalilian, Mohammad Amin Tabatabaiefar, Mahboubeh Yazdanpanah, Elham Darabi, Tayyeb Bahrami, Ali Zekri, Mohammad Reza Noori-Daloii
International journal of molecular and cellular medicine, Volume 7, pp 17-23; doi:10.22088/IJMCM.BUMS.7.1.17

Abstract:
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 of MITF, 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. 31 WS2 patients, including 22 men and 9 women from 14 families were included. Waardenburg consortium guidelines were employed for WS2 diagnosis. WS2 patients underwent screening for MITF, 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 a de novo heterozygous c.640C>T (p.R214X) in MITF and a de novo heterozygous 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.
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