فهرست مطالب
Iranian Journal of Basic Medical Sciences
Volume:24 Issue: 3, Mar 2021
- تاریخ انتشار: 1399/12/10
- تعداد عناوین: 17
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Pages 264-266Prevention and treatment of the Human T-cell leukemia virus, type 1 (HTLV-1) which was discovered nearly 40 years ago, still remain challenging. The reported high prevalence of HTLV-1 in some countries around the world triggered an open letter to the World Health Organization (WHO), urging action against HTLV-1 infection in 2018. This highlights the importance of virus elimination strategies to eradicate HTLV-1 infection. In Iran, we have documented our experiences with the virus in order to achieve and promote the possible ways to manage, control, and eliminate HTLV-1. Although there has been considerable progress apropos of HTLV-1, a series of additional challenges need to be tackled to control HTLV-1 infection in Iran.Keywords: ATL HAM, TSP HTLV, 1 Prevention Treatments
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Pages 267-279
Diabetic retinopathy (DR) is ocular microvascular complications of diabetes mellitus. Along with the increasing prevalence of diabetes worldwide, DR has come into the major cause of human blindness. Several studies have demonstrated the important roles of the expression alteration in the proteins contributed to vascular dysfunction during DR, especially vascular endothelial growth factor (VEGF). However, there is a need for further mechanistic research in this context to design new therapeutic and diagnostic programs. MicroRNAs (miRNAs, miRs) have been introduced as key controllers of gene expression in a variety of biological processes including differentiation, proliferation, and metabolism. Altered expression of miRNAs during DR development indicates a close relationship between these regulatory molecules and DR through regulating gene expressions. This review discusses and updates the functions of miRNA-dependent pathways and key roles of VEGF in the DR, which may increase our understanding and ability to target these small but important molecules to efficiently improve therapeutic and diagnostic approaches.
Keywords: Diabetic retinopathy, Gene regulation, Molecular targeting, miRNAs, VEGF -
Pages 280-292
Metabolic syndrome is a condition associated with obesity, diabetes, dyslipidemia, and high blood pressure. Recently, the use of phytochemicals is suggested in the control and treatment of metabolic syndrome. The Azadirachta indica (neem) is an evergreen tree belonging to the family of Meliaceae. Multiple studies have been confirmed the anti-diabetic and anti-hypertension, anti-hyperlipidemia, and anti-obesity effects of neem. In this review, we reported the protective effects of neem against the complications of metabolic syndrome with a special focus on mechanisms that are involved. It has been shown that neem can control hyperglycemia and hypertension through over-expression of transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2) and anti-oxidant effects. Neem also reduced the glucose uptake through up-regulation of glucose transporter 4 (GLUT4) and inhibition of key intestinal enzymes such as glucosidases. Moreover, neem showed anti-hypertensive effects possibility via the block of calcium channels, up-regulation of endothelial nitric oxide synthase (eNOS), and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathway. Anti-oxidant effects play an important role in protective mechanisms of neem against metabolic syndrome and its complications.
Keywords: Azadirachta indica, Diabetes, Hyperlipidemia, Hypertension, metabolic syndrome, Neem, Obesity -
Pages 293-299Objective(s)Metabolic syndrome (MS) is a cause of death worldwide. The hepatic nuclear factor- NF-kβ (NF-kβ) is the cardinal player of hepatic homeostasis, insulin sensitivity, and lipid metabolism. Thus, we investigated the effect of thiamine on hepatic gene expression of NF-kβ and its levels of activators in MS rats.Materials and MethodsMale Wistar rats were randomly divided into 4 equal groups (ten rats in each group): normal, MS, and two alike groups under thiamine treatment. MS was induced in rats with a high sucrose solution (40 % in drinking water) for 4 months. Treated groups of rats received 0.18 % of thiamine daily in drinking water. Hematoxylin-Eosin stains were employed to determine the histopathological changes of the liver. Metabolic profile, glycation products, oxidative stress, inflammatory markers, the activity of glyoxalase-I, as well as NF-kβ hepatic expression of all rat groups, were determined.ResultsAcute hepatitis was not observed in the livers of the thiamine treated MS rats. Besides, the treatment showed an advantageous effect on glucose, lipid metabolism, and body weight via down-regulation of hepatic NF-kβ and induction of glyoxalase system activity. Furthermore, the treatment decreased diverse glycation, oxidative stress, and inflammatory markers (P>0.001).ConclusionThiamine decreased body weight and improved metabolism and activity of glyoxalase-I in MS rats with anti-glycation, antioxidant, and anti-inflammatory activities. Further, the treatment had a hepato-protective effect via reduction of NF-kβ signaling.Keywords: Glycation Glyoxalase, I Metabolic syndrome Nuclear factor, kβ Thiamine
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Pages 300-311Objective(s)Hypercholesterolemia is correlated with brain amyloid-β (Aβ) deposition and impaired cognitive functions and contributes to Alzheimer’s disease. Effects of cholesterol-lowering dill tablets and aqueous extract of Ocimum basilicum L. (basil) on learning and memory and hippocampus fatty acid composition were examined. mRNA levels of the genes involved in cholesterol homeostasis were also determined in high-cholesterol diet (HCD) fed rats.Materials and MethodsForty male Wistar rats were allocated to 4 groups: rats fed chow diet (C); rats fed high-cholesterol (2%) diet (HCD); rats treated with HCD+300 mg/kg dill tablets (HCD+Dill); and finally, rats fed HCD and treated with 400 mg/kg basil aqueous extract (HCD+basil). Treatment was carried out for 16 weeks. Hippocampus Aβ(1-42) level was determined. Spatial and passive avoidance tests were used to examine cognitive functions. Hippocampal FA composition was assessed by gas chromatography. Basil aqueous extract was analyzed by GC-double mass spectroscopy (GC-MS/MS) and expression of LXR-α, LXR-β, and ABCA1 genes was assessed by qRT-PCR.ResultsDill tablets and basil extract remarkably ameliorated serum cholesterol (p <0.001), retarded hippocampal accumulation of Aβ, and attenuated HCD-induced memory impairment. Hippocampus FA composition did not change but serum cholesterol was found positively correlated with hippocampus Aβ(1-42) (p <0.001), total n 6 PUFA (P=0.013), and Aβ(1-42) showed correlation with the ratio of n6 to n3 PUFA. At least 70 components were identified in basil aqueous extract.ConclusionDill tablets and aqueous extract of basil attenuated the hypercholesterolemia-induced memory impairment by lowering serum cholesterol and hippocampus amyloid deposits, and probably beneficial in AD adjuvant therapy.Keywords: Alzheimer’s disease, Dill, Hypercholesterolemia, Learning, Memory, Ocimum
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Pages 312-321Objective(s)Acrylamide is a toxic compound that forms during food processing at high temperatures. Acrylamide has been shown to induce toxicity in various organs in the body. This study aimed to investigate the effect of acrylamide exposure on the susceptibility of the colon to ulcerative colitis in a mouse model.Materials and MethodsMice were pretreated with acrylamide (oral, 20 and 30 mg/kg/day) for 21 consecutive days, and colitis was induced by intrarectal administration of acetic acid.ResultsThe results revealed that acrylamide-pretreatment significantly increased disease activity index (DAI), macroscopic damage, histological changes of the colonic mucosa and oxidative stress markers carbonyl protein, malondialdehyde (MDA), and nitric oxide (NO), whereas it decreased the levels of anti-oxidants glutathione (GSH), superoxide dismutase (SOD) and catalase. Moreover, induction of colitis in acrylamide-pretreated mice caused a higher increase in colonic levels of myeloperoxidase (MPO), matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-1, cytochrome-c, caspase-3, proinflammatory cytokine tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and interferon (IFN)-γ, whereas it reduced the level of IL-10. The mRNA expression of nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) were further increased in colon tissue of mice exposed to acrylamide.ConclusionThese findings suggest that acrylamide can accelerate the development of acetic acid-induced colitis. In conclusion, chronic acrylamide exposure may aggravate the severity of ulcerative colitis and increase colonic mucosal damage through oxidative stress and inflammatory responses.Keywords: Acrylamide, Apoptosis, Cytokines, Inflammation, Oxidative stress, Ulcerative colitis
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Pages 322-330Objective(s)
Electromagnetic field (EMF) emitted by mobiles may affect the male reproductive system. Selenium, as an antioxidant, may protect against electromagnetic field-induced tissue damage. Theis study aimed to investigate the effects of selenium on rat testis exposed to electromagnetic fields.
Materials and MethodsTwenty-four male Wistar rats were divided into four groups, namely EM group (2100 MHZ), EM/SE group (2100 MHZ + selenium (0.2 mg/kg), SE group (selenium 0.2 mg/kg), CONT (control group). Serum LH, FSH, testosterone, leptin and aromatase levels, testis weight and volume index, sperm parameters (count and abnormal percent), seminiferous tubule diam eters, germinal epithelia thickness, immunoreactivity of leptin receptor and caspase-3 (for apoptotic cells in germinal epithelium) were investigated.
ResultsOur results showed that serum LH, FSH, GnRH, testosterone level, sperm count, germinal epithelium thickness, and seminiferous tubule diameter were significantly declined in the EM group compared with the CONT group (P<0.05). However, in the EM group, the serum leptin level, sperm abnormality, aromatase enzyme level, apoptotic cells, and leptin receptor were increased compared with the CONT group (P<0.05). Furthermore, an increase in sperm count, germinal epithelium thickness, seminiferous diameters, serum LH, FSH, and GnRH, and testosterone levels, and a significant decrease in sperm abnormality, leptin receptor and apoptotic cells in the EM/SE group compared with the EM group were also observed (P<0.05).
ConclusionThis study showed that electromagnetic radiation may have detrimental impacts on the male reproductive system, which can be prevented by use of selenium.
Keywords: Apoptosis, Electromagnetic Radiation, Leptin receptor, Selenium, Testis -
Pages 331-340Objective(s)Ocular inserts are usually polymeric thin films with increased ocular residence time and sustained drug release capacity. Sodium alginate is a biocompatible and biodegradable carrier; however, initial burst release of encapsulated drug within it, is recognized as a challenge. Grafting –addition of functional moieties to a polymer– is a technique to modify polymers’ physicochemical properties, including higher ability to control drug release. Linezolid (LNZ) solution is used in consecutive doses in treatment of antibiotic-resistant Gram-positive bacterial infections especially induced by methicillin resistant Staphylococcus aureus (MRSA).Materials and MethodsGrafted alginate copolymers were synthesized using butyl methacrylate (BMC) and lauryl methacrylate (LMC) at two different reaction times (12 hr and 24 hr). Copolymerization was evaluated by 1H-NMR, Ft-IR, and TGA. Copolymer safety was examined by cytotoxicity test against HEK-293 cell. Linezolid inserts were prepared using optimized copolymers and characterized.Results1H-NMR, Ft-IR, and TGA confirmed the successful grafting of alginate copolymers. ALG-B24 and ALG-L12 showed the highest safety against HEK-293 cell line comparing with intact alginate. Linezolid insert characterization results indicated a slower linezolid release profile related to creation of a lipophilic structure. A better strength property for linezolid loaded ALG-B24 and ALG-L12 inserts was obtained while ALG-L12 showed a stronger adhesive force compared with intact alginate. Antibacterial efficacy on clinical isolated MRSA after 24 hr was similar to linezolid solution.ConclusionLipophilic alginate copolymer (ALG-L12) showed a sustained release capability while retaining its main feature in strong film forming ability so it seems to be a promising safe carrier.Keywords: Copolymer, Grafting, Linezolid, Ocular insert, Sodium alginate
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Pages 341-348Objective(s)
We aimed to observe the effects of preventive electroacupuncture (EA) on the microbiota–gut–brain axis and spatial learning and memory deficits and to investigate the possible mechanism using D-galactose (D-gal)-induced aging rats.
Materials and MethodsD-gal was intraperitoneally injected to establish the aging model. We used Morris water maze to detect spatial learning and memory function of rats. RT-PCR was applied to test targeted gut microbes. The expression of zonula occludens-1 (ZO-1) and Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB pathway proteins were detected by Western blotting. ELISA was employed to evaluate the level of lipopolysaccharides (LPS), diamine oxidase (DAO) and S-100β. Additionally, we observed ionized calcium-binding adapter molecule-1 (Iba-1) expression in the hippocampal CA1 area by immunofluorescence.
ResultsMorris water maze test showed decreased mean escape latency and increased target quadrant time after EA treatment. The gut microbiota composition has been modified in EA treated rats. Molecular examination indicated that expression of ZO-1 was improved and the the concentration of LPS in blood and hippocampus were reduced in EA treated rats. Further, we observed an inhibition of activated microglia and TLR4/NF-κB pathway in EA groups.
ConclusionPreventive EA may alleviate the impairments of the microbiota–gut–brain axis and spatial learning and memory in aging, and the mechanism may be related to the inhibition of TLR4/NF-kB signaling pathway. The combination of acupoints GV20 and ST36 can enhance the therapeutic effect in aging rats.
Keywords: Aging Alzheimer’s disease Electroacupuncture Microbiota, Gut, brain axis NF, κB TLR4 -
Pages 349-359Objective(s)
The contribution of classic progesterone receptors (PR) in interceding the neuroprotective efficacy of progesterone (P4) on the prevention of brain edema and long-time behavioral disturbances was assessed in traumatic brain injury (TBI).
Materials and MethodsFemale Wistar rats were ovariectomized and apportioned into 6 groups: sham, TBI, oil, P4, vehicle, and RU486. P4 or oil was injected following TBI. The antagonist of PR (RU486) or DMSO was administered before TBI. The brain edema and destruction of the blood-brain barrier (BBB) were determined. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), and beam walk (BW) task were evaluated previously and at various times post-trauma. Long-time locomotor and cognitive consequences were measured one day before and on days 3, 7, 14, and 21 after the trauma.
ResultsRU486 eliminated the inhibitory effects of P4 on brain edema and BBB leakage (p <0.05, p <0.001, respectively). RU486 inhibited the decremental effect of P4 on ICP as well as the increasing effect of P4 on CPP (p <0.001) after TBI. Also, RU486 inhibited the effect of P4 on the increase in traversal time and reduction in vestibulomotor score in the BW task (p <0.001). TBI induced motor, cognitive, and anxiety-like disorders, which lasted for 3 weeks after TBI; but, P4 prevented these cognitive and behavioral abnormalities (p <0.05), and RU486 opposed this P4 effect (p <0.001).
ConclusionThe classic progesterone receptors have neuroprotective effects and prevent long-time behavioral and memory deficiency after brain trauma.
Keywords: Behavioral disorders, Mifepristone, Neuroprotection, Progesterone, Spatial Memory, TBI -
Pages 360-368Objective(s)
IL-2Rα plays a critical role in maintaining immune function. However, expression and secretion of CD25 in various malignant disorders and autoimmune diseases are now well established. Thus, CD25 is considered an important target candidate for antibody-based therapy. This study aimed to find the most suitable linker peptide to construct a functional anti-CD25 single-chain fragment variable (scFv) by bioinformatics studies and its production in a bacterial expression system.
Materials and MethodsHere, the 3D structures of the scFvs with different linkers were predicted and molecular dynamics simulation was performed to compare their structures and dynamics. Then, interactions between five models of scFv and human CD25 were calculated via molecular docking. According to MD and docking results, the anti-CD25 scFvs with (Gly4Ser)3 linker were constructed and cloned into pET-22b(+). Then, recombinant plasmids were transformed into Escherichia coli Bl21 (DE3) for expression using IPTG and lactose as inducers. Anti-CD25 scFv was purified from the periplasm and detected by SDS-PAGE and Western blot. Afterward, functionality was evaluated using ELISA.
ResultsIn silico analysis showed that the model containing (Gly4Ser)3 as a linker has more stability compared with other linkers. The results of SDS-PAGE, Western blot, and ELISA confirmed the accuracy of anti-CD25 scFv production and its ability to bind to the human CD25.
ConclusionConclusively, our work provides a theoretical and experimental basis for production of an anti-CD25 scFv, which may be applied for various malignant disorders and autoimmune diseases.
Keywords: CD25 Daclizumab IL, 2Rα Protein engineering Single, chain variable fragment (scFv) -
Pages 369-376Objective(s)There are still challenges regarding c-kit+ cells’ therapeutic outcome in the clinical setting. Here, we examined the c-kit+ cell effect on the alleviation of asthma by modulating miRNAs expression.Materials and MethodsTo induce asthma, male rats were exposed to ovalbumin. Bone marrow-derived c-kit+ cells were enriched by MACS. Animals were classified into four groups (6 rats each). Control rats received PBS intratracheally; Ovalbumin-sensitized rats received PBS intratracheally; Ovalbumin-sensitized rats received PBS intratracheally containing 3×105 c-kit+ and c-kit- cells. Cells were stained with Dil fluorescent dye to track in vivo condition. Pathological changes were monitored in asthmatic rats after transplantation of c-kit+ and c-kit- cells. Serum levels of IL-4 and INF-γ were measured by ELISA. Transcription of miRNAs (-126 and 133) was assessed by real-time PCR analysis.ResultsPathological examination and Th1 and Th2 associated cytokine fluctuation confirmed the occurrence of asthma in rats indicated by chronic changes and prominent inflammation compared with the control group (p <0.05). Both c-kit+ and c-kit- cells were verified in pulmonary niche. Administration of c-kit positive cells had the potential to change INF-γ/IL-4 ratio close to the normal values compared with matched-control asthmatic rats (p <0.05). We also found that c-kit+ cells regulated the expression of miRNA-126 and -133, indicated by an increase of miRNA-133 and decrease of miRNA-126 compared with cell-free sensitized groups (p <0.05).Conclusionc-kit- cells were unable to promote any therapeutic outcomes in the asthmatic milieu. c-kit+ cells had the potential to diminish asthma-related pathologies presumably by controlling the transcription of miRNA-126 and -133.Keywords: Cell therapy, Histological changes, Lung, Ovalbumin, Rat
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Pages 377-382Objective(s)HIV-1 is still considered a serious threat to human health, and accessibility of a suitable and efficient vaccine is urgently needed to address the disease burden. DNA vaccines employ the cells of the vaccinated hosts for in situ production of the vaccines. This strategy is an alternative and effective approach for traditional vaccination against high-risk pathogens, e.g., HIV-1. On the other hand, polyepitope vaccines, containing several immunogenic and conserved epitopes from virus vital regulatory and structural proteins, could more efficiently induce cellular and humoral immune responses against different clades of the virus.Materials and MethodsHerein, we comparatively investigated the immunogenic potency of the HIV-1 polytope DNA vaccine containing CpG oligodeoxynucleotides (CpG-ODNs) in BALB/c mice. To this end, after verifying the expression of the recombinant sequence in the eukaryotic HEK 293 cell line, it was amplified and extracted in the prokaryotic host cells (E. coli DH5α)) and then formulated and administered intramuscularly (IM) to the experimental mice (on days 0, 14, and 28) with and without CpG-ODNs adjuvant.ResultsTaken together, the results demonstrated that CpG-ODNs adjuvanted DNA vaccine could significantly elicit cellular and humoral immune responses in the immunized animals in comparison with the control ones (p <0.05).ConclusionRegarding the obtained results and also considering the advantages of polytopic and DNA vaccines, this approach might be considered a new regimen in HIV-1/AIDS vaccination.Keywords: Cellular immunity CpG oligodeoxynucleotides DNA vaccine HIV, 1 Humoral immunity
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Pages 383-390Objective(s)
Doxorubicin (Dox) is one of the most well-known chemotherapeutics that are commonly applied for a wide range of cancer treatments. However, in most cases, efflux pumps like P-glycoprotein (P-gp), expel the taken drugs out of the cell and decrease the Dox bioavailability. Expression of P-gp is associated with elevated mRNA expression of the ATP-binding cassette B1 (ABCB1) gene.
Materials and MethodsIn the current study, different sequences of cell-penetrating peptides (CPPs) containing tryptophan, lysine, and arginine and their nano-complexes were synthesized and their impact on the expression and activity of the ABCB1 gene was evaluated in the A549 lung carcinoma cell line. Furthermore, the cellular uptake of designed CPPs in the A549 cell line was assessed.
ResultsThe designed peptides, including [W4K4], [WR]3-QGR, R10, and K10 increased Dox cytotoxicity after 48 hr. Furthermore, arginine-rich peptides showed higher cellular uptake. Rhodamin123 accumulation studies illustrated that all the obtained peptides could successfully inhibit the P-gp pump. The designed peptides inhibited the ABCB1 gene expression, of which, [W4K4] resulted in the lowest expression ratio.
Conclusion[W4K4], [WR]3-QGR, R10, and K10 could successfully increase the Dox cytotoxicity by decreasing the efflux pump gene expression.
Keywords: Cancer therapy CPPs Doxorubicin Multi, drug resistance P, gp -
Pages 391-399Objective(s)
Many patients die due to vascular, gastrointestinal lumen problems, and coronary heart diseases. Synthetic vessels that are made of biodegradable-nanofiber polymers have significant properties such as proper biodegradability and efficient physical properties such as high strength and flexibility. Some of the best options for supporting cells in soft tissue engineering and design are applications of thermoplastic polyurethane polymer in the venous tissue. In this study, the first nanoparticle-reinforced polymeric artificial prosthesis was designed and tested to be used in the human body.
Materials and MethodsIn this study, artificial gastrointestinal lumen were fabricated and prepared using a 3D printer. To improve cell adhesion, wettability properties and mechanical stability of elastin biopolymer with magnetic nanoparticles (MNPs) as well as single-walled carbon nanotubes (SWCNT) were prepared as separate filaments. MNPs were made in 5–7 mm sizes and then examined for mechanical, biological, and hyperthermia properties. Then, the obtained results of the gastrointestinal lumen were simulated using the Abaqus software package with a three-branch. The results were evaluated by X-ray diffraction (XRD) and scanning electron microscopy (SEM) for morphology and phase analysis.
ResultsThe obtained results of the designed vessels showed remarkable improvement in mechanical properties of the SWCNT vessels and hyperthermia properties of the vessels containing the MNPs. The results of computational fluid dynamics (CFD) analysis showed that the artificial vessels had lower shear stress at the output.
ConclusionFive-mm MNP containing vessels showed noticeable chemical and biological properties along with ideal magnetic results in the treatment of thrombosis and vascular obstruction.
Keywords: Cardiovascular, Gastrointestinal lumen, Magnetite nanoparticle, Polyurethane, tissue -
Pages 400-407Objective(s)Emergence of multidrug resistance has reduced the choice of antimicrobial regimens for UTIs. To understand the association of phenotype and genotype among uropathogens.Materials and MethodsSix hundred and twenty-eight (628) urine samples were collected and analyzed. Antibiotic sensitivity pattern was determined by the Kirby-Bauer Disc Diffusion Method and minimum inhibitory concentration (MIC) was tested by the E test. Fluoroquinolone resistant mutations in QRDR of gyrA and ParC, phylogenetic groups, and PAIusp subtype were detected by PCR.ResultsMost prevalent uropathogens were Escherichia coli (53.2%) followed by Klebsiella pneumoniae (21%). Multidrug- resistance was observed in > 50% cases for third-generation cephalosporins and ciprofloxacin and lowest in meropenem. E. coli (66.2%) and K. pneumonia (64.4%) were extended-spectrum β-lactamases (ESBLs) producers. MIC to trimethoprim-sulfamethoxazole was highest in E. coli (>1024 µg/ml). In 80 (24%) of the 334 E. coli isolates analyzed in detail, 54 fluoroquinolones (FQ) resistant isolates carried mutations (S83L, D87N, S80I, E84V) in QRDR of gyrA and ParC. Out of 54 FQ-resistant isolates, 43 (79.6%) isolates belonged to the phylogenetic group B2, and 11(20.4%) belonged to group D. Isolates belonged to group B2, 38 (88.4%) of the 43 isolates carried PAIusp subtype IIa and high frequency of mutation E84V in ParC was detected in 37 (97.4%). Other mutations, such as S80I, S83L in gyrA and D87N in ParC were found in all resistant isolates.ConclusionCorrelations between phenotype and genotype provided a basis to understand the resistance development in uropathogens, and PAIusp subtyping indicated that E. coli belonged to the B2 group.Keywords: Escherichia coli, ESBL, MDR, PCR, UTI
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Pages 408-419Objective(s)
We investigated whether NOS3-c.894G>T transversion (rs1799983), which causes the substitution of glutamate with aspartate (E298D) in the oxygenase domain of endothelial nitric oxide synthase (eNOS), is associated with susceptibility to metabolic syndrome (MetS) risk in Iranian-Azerbaijanis.
Materials and MethodsThe frequencies of the alleles and genotypes were compared in the 300 cases and 300 controls using PCR-RFLP assay. Also, higher-order MetS interaction with the genotypes, gender, age, and body mass index (BMI) was evaluated by classification and regression tree (CART) analysis. In silico analysis was done to introduce a hypothesis describing the molecular effects of NOS3-c.894G>T.
ResultsThe T allele (OR:1.46; CI:1.054-2.04; P=0.02), GT genotype (OR:1.44; CI:1.02-2.03; P=0.03), and dominant model (TT+GT vs GG, OR:1.48; CI:1.06-2.06; P=0.01) were found to be associated with increased risk of MetS. In the male subpopulation TT genotype (OR:7.19; CI:1.53-33.70; P=0.01) was discovered to be associated with increased odds of MetS. CART analysis showed that NOS3-c.894G>T genotypes and BMI significantly contribute to modulating MetS risk. Furthermore, in silico investigation revealed that c.894G>T may alter eNOS function through affecting interactions of its oxygenase domain with proteins such as B2R, b-actin, CALM1, CAV1, GIT1, HSP90AA1, NOSIP, and NOSTRIN.
ConclusionWe showed that NOS3-c.894G>T was associated with an increased risk of MetS in Iranian-Azerbaijanis, and BMI modulates the effects of NOS3-c.894G>T genotypes on MetS risk. Also, in silico analysis found that NOS3-c.894G>T may affect the interaction of the eNOS oxygenase domain with its several functional partners.
Keywords: Azar, cohort Bioinformatics Metabolic syndrome Nitric oxide pathway rs1799983