فهرست مطالب
Avicenna Journal of Medical Biotechnology
Volume:11 Issue: 3, Jul-Sep 2019
- تاریخ انتشار: 1398/04/01
- تعداد عناوین: 11
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Page 1Despite the advent of several antidepressant medications, treatment of Major Depressive Disorder (MDD) is still far from optimal 1-3. A large proportion of patients with MDD do not respond to their first medication. To achieve favorable response, these patients are generally treated with either switching to another treatment or augmentation therapy. In the recent decade, several augmentative strategies for treatment of MDD have been developed. Some of these treatment modalities focus on recently developed hypotheses of pathophysiological processes in patients with MDD 1-3. These mainly include immune system dysfunction, hypothalamic-pituitary-adrenal (HPA) axis and metabolic derangements, impaired neuroprotection, or neuroinflammation 1-3.
Growing body of evidence suggests that inflammation is implicated in the pathophysiology of MDD 4-6. Sickness be-havior which is a result of inflammatory activation, shares many clinical features such as anhedonia, anorexia, irritability, and mild cognitive problems with MDD 4-6. Several studies have shown an elevation of proinflammatory cytokines [particularly IL-6 and Tumor Necrosis Factor (TNF-α)] in patients with MDD 7. A large body of research now suggests that depression is associated with a low-grade, chronic inflammatory response and is accompanied by increased oxidative stress.
• depression frequently is comorbid with many inflammatory illnesses
• increased inflammatory biomarkers are associated with major depressive disorder (MDD)
• exposure to immunomodulating agents may increase the risk of developing depression
• stress can activate proinflammatory pathways
• antidepressants can decrease inflammatory response
• inhibition of inflammatory pathways can improve mood 4-7.
IL-6 is one of the most widely studied cytokines in patients with MDD 8,9. In addition to elevation of this cytokine in patients with MDD, relation of IL-6 concentration to severity of depression, a shift in circadian rhythm 8,9, and a reduction in its concentration in response to antidepressants have been shown in several studies.
Previous studies have already shown that elevated levels of inflammation are associated with poor response to antidepressants. The scientists found that they could pinpoint a threshold and precisely predict which patients would respond to conventional antidepressants. None of the patients with MIF and IL-1β levels above the threshold responded to the antidepressants most often prescribed. Those with inflammation levels below the threshold would likely respond. One reason for the lack of predictive biomarkers in MDD is that little is known with absolute certainty about how antidepressants improve mood. All currently approved medications for depression act in a similar way, increasing the availability of monoamine neurotransmitters like serotonin in the brain. Psychiatrists continue to search for biomarkers to help guide therapy and, potentially, improve chances of discovering new drugs 9.
In conclusion, the link between depression and the body's inflammatory response continues getting stronger, with more research showing an ever-tighter correlation. -
Pages 208-214BackgroundMarine environment is a valuable source of bioactive compounds with variable medicinal properties. Previously, it was shown that Ophiocoma erinaceus extracted polysaccharide has prominent cytotoxic effect on HeLa human cervical cancer cells. In the present study, the anti-cancer properties of polysaccharide extracted from Ophiocoma scolopendrina (O. scolopendrina) were examined in comparison with paclitaxel as a conventional drug against resistant ovarian cancer; also, its related mechanism against A2780cp ovarian cancer cells was investigated.MethodsThe A2780cp cancer cells and NIH3T3 normal cells were cultured and treated with different concentrations of polysaccharide extracted from O. scolopendrina for 24 hr and 48 hr. Then, cell toxicity was studied by MTT assay, morphology of cells was observed under inverted microscopy and the type of induced cancer cell death was assessed by annexin V-FITC, propodium iodide and acridine orange staining. Finally, the apoptosis pathway was determined by measurement of caspase-3 and caspase-9 activity and assessment of p53 and Bcl-2. The statistical analysis was performed by SPSS software, one way ANOVA and p<0.05 was considered significant.ResultsOur observations from MTT assay and morphological assessment exhibited that O. scolopendrina isolated polysaccharide inhibited proliferation of ovarian cancer cells with IC50 of 35 µg/ml, while paclitaxel suppressed tumor cell growth with IC50=10 µg/ml. In contrast, MTT observations revealed low cytotoxicity of these chemotherapeutic agents against NIH3T3 normal cells. Also, the analysis correlated with induced cell death elucidated that concurrent treatment of polysaccharide plus paclitaxel had a further anti-cancer effect against A2780cp cells mainly through restoration of p53 and mitochondrial apoptosis cell death induction.ConclusionTaken together, our research supports the finding that application of polysaccharide extracted from O. scolopendrina can be considered a promising marine chemotherapeutic approach for advancing efficacy of paclitaxel in treatment of resistant ovarian cancer. Additional in vivo experiments are required to elucidate the role of brittle star polysaccharides in animal and clinical trials.Keywords: Apoptosis, Ovarian neoplasms, Paclitaxel
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Pages 215-220BackgroundAlthough Saccharomyces cerevisiae has several industrial applications, there are still fundamental problems associated with sequential use of carbon sources. As such, glucose repression effect can direct metabolism of yeast to preferably anaerobic conditions. This leads to higher ethanol production and less efficient production of recombinant products. The general glucose repression system is constituted by MIG1, TUP1 and SSN6 factors. The role of MIG1 is known in glucose repression but the evaluation of effects on aerobic/anaerobic metabolism by deletion of MIG1 and constructing an optimal strain brand remains unclear and an objective to be explored.MethodsTo find the impact of MIG1 in induction of glucose-repression, the Mig1 disruptant strain (∆MIG1) was produced for comparing with its congenic wild-type strain (2805). The analysis approached for changes in the rate of glucose consumption, biomass yield, cell protein contents, ethanol and intermediate metabolites production. The MIG1 disruptant strain exhibited 25% glucose utilization, 12% biomass growth rate and 22% protein content over the wild type. The shift to respiratory pathway has been demonstrated by 122.86 and 40% increase of glycerol and pyruvate production, respectively as oxidative metabolites, while the reduction of fermentative metabolites such as acetate 35.48 and ethanol 24%.ResultsResults suggest that ∆MIG1 compared to the wild-type strain can significantly present less effects of glucose repression.ConclusionThe constructed strain has more efficient growth in aerobic cultivations and it can be a potential host for biotechnological recombinant yields and industrial interests.Keywords: Saccharomyces cerevisiae, Homologous recombination, Metabolic pathways, Yeasts
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Pages 221-228BackgroundIntrafamilial spread of Hepatitis B virus (HBV) infection in Iran has only been investigated with serological testing without using molecular studies as the most informative and definitive type of analysis.MethodsIn the present study, intrafamilial transmission of HBV among family members of Iranian index HBsAg carriers was investigated using phylogenetic analysis of the S region of the viral genome. Nested polymerase chain reaction was used for detection of HBV DNA in serum samples from 22 index and 43 contact patients with chronic HBV infection. HBV DNA was detected in 37 samples (14 indexes, 23 contacts). The S gene region of the DNA isolates was subjected to direct sequencing and phylogenetic analysis by Bioedit, Mega and Phylip programs.ResultsAll isolates (from 26 patients) were clustered with genotype D, of which 24 strains were of subgenotype D1, subtype ayw2, while 2 additional strains were of subgenotype D2, subtype ayw3. Evidence of intrafamilial transmission of the virus was found in 8 families studied phylogenetically. Overall, 60 changes were detected in the amino acid sequences of the surface antigen protein in 23 patients. Four premature stop codons occurred in 3 isolates at residues 69 and 182. Seven out of 8 families displayed 25−100% common amino acid substitutions among their members.ConclusionOur data corroborated intrafamilial transmission of HBV, as evidenced by concordant HBV genotype among household members, viral sequence homology and close genetic relatedness of the strains on the phylogenetic tree, and horizontal transmission of S gene mutations among family members.Keywords: Genotype_Hepatitis B virus_Phylogenetic analysis_Surface antigen_Transmission
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Pages 229-233BackgroundSome products of bacteria are reported as an immunomodulator. The Helicobacter pylori (H. pylori) outer membrane proteins play an important role in stimulation of immune system. The present study was performed to determine the in vitro effect of recombinant HopH of H. pylori on Nitric Oxide (NO) production and viability of mouse peritoneal macrophages.MethodsH. pylori recombinant HopH was produced in this study. Mice peritoneal macrophages were purified and cultured. Different concentrations of recombinant HopH were used for stimulation of macrophages in order to evaluate NO production. The cell viability was detected by MTT assay. NO amounts released in to the supernatants of cultured macrophages and LPS-stimulated macrophages (10 μg/ml) were detected by Griess reagent.ResultsResults demonstrated that the suppressive effect of high concentrations of recombinant HopH on NO release and the stimulation effect of protein was shown in 15 µg/ml, compared to the control group. NO stimulation was significant in all the concentrations of LPS stimulated with HopH groups.ConclusionAccording to our findings, recombinant HopH has a toxic effect in high concentration on cell. So it can be an anticancer candidate.Keywords: Helicobacter pylori, Macrophage, Recombinant HopH
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Pages 234-238BackgroundPatients with diabetes present with lipid disorders, including hypercholesterolemia, which can be a high-risk factor for atherosclerosis. Recently, increasing interest has been focused on anti-lipidemic function of herbal medicines, especially Zingiber officinale (known as ginger), in diabetes. However, the mechanism underlying the effect of ginger on some players involved in cholesterol homeostasis of Central Nervous System (CNS) among diabetic patients remains unclear. To our knowledge, this is the first study to investigate the effect of ginger on brain regulation of Hydroxymethylglutaryl-CoA Reductase (HMG-CoA reductase) and Cholesterol 24-hydroxylase (CYP46A1), which provides a rational model for understanding brain dyslipidemia mechanisms associated with diabetes.MethodsBrains of rats were isolated from four groups: control, non-treated diabetic, and treated diabetic groups receiving 200 or 400 mg/kg of hydroalcoholic extracts of ginger for eight weeks. HMG-CoA reductase and CYP46A1 levels in brain homogenates were determined by western-blot technique.ResultsGinger root extract caused a significant decrease in HMG-CoA reductase and an increase in CYP46A1 levels in treated diabetic groups compared to diabetic control. In comparison to diabetic group, these effects were more remarkable with 400 mg/kg concentration of ginger extract.ConclusionThe findings showed that ginger extract has a regulatory effect on proteins involved in cholesterol homeostasis in CNS by a significant down- and up-regulation of HMG-CoA reductase and CYP46A1 levels, respectively. It can be suggested that adding ginger to daily diet of diabetic patients has useful effects and may ameliorate diabetes complications.Keywords: Brain, Cholesterol 24-hydroxylase, Diabetes mellitus, Ginger, Hydroxymethylglutaryl-CoA reductases
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Pages 239-244BackgroundType 2 Diabetes Mellitus (T2DM) is a serious problem in the world. 5-Hydroxytryptamine (5-HT, serotonin) plays an important role in obesity, glucose control and insulin resistance. The polymorphism of the serotonin transporter gene linked promoter region (5-HTTLPR) might influence 5-HTT expression and serotonin uptake. The polymorphism results in two alleles of L (Long) and S (Short). The aim of the present study was to evaluate the association between 5-HTTLPR genotypes in type 2 diabetes mellitus (T2DM), obesity as well as serum biochemical profiles in Iranian population from 2012 until 2015.Methods180 patients with T2DM and 180 controls were selected and the frequency of S and L alleles was determined by PCR. Then, the relationship between genotypes, body mass index (BMI) and serum biochemical variables was investigated.ResultsThe frequency of S and L alleles in experimental and control groups was the same [for the L allele p=0.754, OR (95%CI)=1.103 (0.597 to 2.041) and for the S allele p=0.906, OR (95%CI)=(0.490 to 1.676)]. However, the mean triglyceride, cholesterol, LDL-C, systolic and diastolic blood pressure levels in the diabetic subjects with LL genotype were significantly higher than LS and SS genotypes (p<0.001) in this population.ConclusionThe L allele of 5-HTTLPR was related to the increased serum lipids and blood pressure in the diabetic patients. However, there was no relationship between the polymorphism of 5-HTTLPR L/S and T2DM in Iranian population.Keywords: 5-HTT gene_5-HTTLPR polymorphism_Serotonin_Type 2 diabetes mellitus
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Pages 245-252BackgroundIn the process of sperm cryopreservation, apart from cryoinjury, the production of Reactive Oxygen Species (ROS) can adversely affect the integrity of chromatin and cellular membranes. Addition of natural antioxidants to freezing me-dium is an approach to reduce the destructive effects of ROS on sperm.MethodsIn this study, during 60 min of cooling process, the ejaculates of five stallions were diluted in the following media: INRA 82 medium as Control (C), INRA 82 medium supplemented with 0.25% Sericin (S), INRA 82 medium supplemented with 1.5 mM Glutathione (G), and INRA 82 medium supplemented with 0.25% Sericin+1.5 mM Glutathione (S+G).ResultsIn the frozen/thawed sericin supplemented group, while the integrity of DNA and the activity of catalase and Glutathione Peroxidase (GPx) were increased, the lipid peroxidation and midpieceab normality decreased, compared with other groups (p<0.05). The proportions of sperms with abnormal head in group S and the sperm with distal droplet in G and S+G groups decreased, compared with group C (p<0.05). In CTC assay, the percentage of capacitated spermatozoa in treatment groups was lower than control (p<0.01).ConclusionIn conclusion, the presence of sericin in freezing medium of stallion semen could improve sperm DNA integrity and its resistance to ROS and lipid peroxidation.Keywords: Antioxidants, Glutathione, Sericins, Spermatozoa
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Pages 253-258Wiskott-Aldrich Syndrome (WAS) is a rare X-linked recessive Primary Immunodeficiency (PID) caused by mutations in WAS gene which encodes a protein known as WASp. WASp plays important roles in cytoskeletal functions that compromise multiple aspects of normal cellular activity including proliferation, phagocytosis, immune synapse formation, adhesion and directed migration. WASp defect particularly causes platelets abnormality which is presented in forms of decrease of Mean Platelet Volume (MPV) and thrombocytopenia in most WAS conditions; nevertheless, some studies reported WAS patients with a normal or large size of platelets in recent years. This phenomenon is unique and the exact mechanism of thrombocytopenia with a normal or large size of platelets is still unknown. In this study, Next Generation Sequencing (NGS) was utilized to discover the causing mutation in WAS gene; furthermore, an attempt was made to evaluate the possibility of other mutations or genes especially WASp interacting proteins and inherited platelet disorder genes in patient clinical symptoms for the purpose of understanding the origin of such unique symptom and to perform further analysis if it is required. Therefore, clinical manifestations and immunologic functions of the patient were checked and Whole Exome Sequencing (WES) was performed to analyze all exonic variations which can be associated with patient phenotypes. Finally, a novel de novo mutation in WAS gene which truncates WASp to half of its normal size was determined as the only cause of clinical manifestation.Keywords: Blood platelets, Thrombocytopenia, Whole exome sequencing, Wiskott-Aldrich syndrome
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Pages 259-263BackgroundThe CRISPR/Cas9 genome editing system is a powerful and simple gene editing method. The format of the CRISPR components is one of the important factors in targeting efficiency. Compared to plasmid or mRNA (IVTs) format, using the CRISPR/Cas9 system as Cas9–crRNA–tracrRNA RNP format is more efficient and rapid, especially in minimizing some of the pitfalls of CRISPR-mediated gene editing. In addition to efficient in vivo applications of the CRISPR RNP format in a variety of cell types and organisms, another advantage of this approach is usability for in vitro applications in which the crRNAs in the tracrRNA–crRNA structure guides the Mg2+-dependent RNAdirected DNA endonuclease to introduce double-strand breaks at specific sites in DNA.MethodsHere, Cas9–crRNA–tracrRNA RNP system was used to test the designed crRNAs for in vitro DNA cleavage by Cas9 protein in RAG1, RAG2 and IL2RG genes.ResultsThe results of cleavage reveal theCas9–crRNA–tracrRNA RNP system is a rapid and efficient way to pre-validate the efficiency of CRISPR cleavage with crRNAs designed for RAG1, RAG2 and IL2RG genes.Conclusionone step in vitro cleavage of DNA by CRISPR/Cas9 ribonucleoprotein complex can be used to pre-validate the functionality and relative efficiency of CRISPR system for targeting genes.Keywords: CRISPR-Cas9, In vitro digestion, Ribonucleoprotein
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Pages 264-267BackgroundBrucellosis is still an important health problem in under developing countries and researches for finding efficient vaccine are going on. Brucella melitensis (B. mellitensis) bp26 gene is a good candidate for brucellosis vaccine and investigations showed that Lactococcus lactis (L. lactis) with several positive characteristic are attractive for protein expression as a live delivery vectors. These fast growing bacteria need no aeration, are easy to handle, have no exotoxin, endotoxin and protease, so the cost of culturing is inexpensive.MethodsB. mellitensis bp26 gene was cloned in food grade pNZ 8149 vector and expressed in L. lactis NZ 3900.ResultsResults showed that we can produce a food-grade recombinant L. lactis producing the B. melitensis BP26 protein.ConclusionIn this study, for Future evaluation about ability of L. lactis as a live delivery vector, a food-grade recombinant L. lactis producing the B. melitensis BP26 protein was produced.Keywords: Brucellosis, Exotoxins, Lactococcus lactis, Vaccines