Iranian Journal of Basic Medical Sciences
Volume:22 Issue: 2, Feb 2019

Previous studies have reached different conclusions regarding an association between apolipoprotein E (APOE) polymorphisms and depression. This meta-analysis was designed to clarify these controversies. Literatures were identified reviewing the national and international databases. The eligible articles for meta-analysis were determined by quality assessment and implementation of inclusion/exclusion criteria. This meta-analysis was performed using Review Manager 5.2 software. The odds ratios (ORs) with corresponding 95% confidence interval (CIs) were calculated using a fixed effects model. Funnel plots and Egger’s regression tests were used to assess the publication bias. A total of nine studies that met the inclusion criteria were identified by performing a comprehensive search on the association between APOE polymorphisms and depression. APOE ε4 allele was significantly associated with depression (allele: OR=1.36, 95%CI=1.11-1.66, P=0.003; dominant: OR=1.34, 95%CI=1.06-1.68, P=0.001; recessive: OR= 1.11, 95%CI =0.45-2.76, P=0.82). HAMD scores were higher in depression patients with-APOE ε4 genotype than who without-APOE ε4 genotype (OR=0.96, 95%CI=0.16-1.76, P=0.02). APOE ε4 allele increased the depression risk; depressive patients carrying APOE ε4 allele had more severe depressive symptoms.

Integrons, as a potential element in the distribution and maintenance of drug resistance, have thoroughly been established. It is known that the high prevalence of integrons in multidrug-resistant (MDR) clinical isolates has become a serious public health concern. The objective of the present study was to determine the frequency of different classes of integrons in clinical isolates in Iran. Electronic global databases were systematically searched. The raw data for integrons among bacterial isolates were collected and their prevalence was analyzed using Comprehensive Meta-Analysis V2.0 (Biostat, Englewood, NJ, USA) software. In a comprehensive literature review, 29 eligible studies were determined with their meta-analyses indicating the prevalence of integron class 1 to be 41% (95% CI 36.3-46.1) and integron class 2 as 17.7% (95% CI 13-23.3) in Gram-negative bacteria. The highest prevalence of integron class 1 was reported in Acinetobacter spp (58%) while the highest prevalence of integron class 2 was reported in Shigella isolates (83.7%). The frequencies of class 1 integron in MDR (79%) and non-MDR isolates (41%) were higher than those for class 2 integron in MDR (13.4%) and non-MDR isolates (17.7%). The current systematic review demonstrated the significant presence of integrons among clinical isolates. Our analysis showed that measures such as estimates of the prevalence of this transposable element and diligence in continued surveillance might be necessary to prevent its spread.

It is known that extremely low frequency-pulsed electromagnetic fields (ELF-PEMF) influence multiple cellular and molecular processes. Retinal pigment epithelial (RPE) cells have a significant part in the emergence and pathophysiology of several ocular disorders, such as neovascularization. This study assessed the impact of ELF-PEMF on the proangiogenic features of RPE cells. Primary cultured RPE cells were treated with ELF-PEMF (50 Hz) for three days. Using ELISA assay, we evaluated the effects of treatment on RPE cell proliferation and apoptosis. Also, RT-PCR was used to determine the gene expression of proangiogenic factors, such as matrix metalloproteinase-2 (MMP-2), MMP-9, vascular endothelial growth factors receptor 2 (VEGFR-2), hypoxia-inducible factor 1 (HIF-1α), VEGFA, cathepsin D, connective tissue growth factor (CTGF), E2F3, tissue inhibitors of metalloproteinases 1 (TIMP-1), and TIMP-2. No noticeable changes were observed in cell proliferation and cell death of ELF-PEMF-exposed RPE cells, while transcript levels of proangiogenic genes (HIF-1α, VEGFA, VEGFR-2, CTGF, cathepsin D, TIMP-1, E2F3, MMP-2, and MMP-9) increased significantly. RPE cells are important for homeostasis of the retina. ELF-PEMF increased the gene expression of proangiogenic factors in RPE cells, which highlights concerns about the impact of this treatment on human health.

Hydatidosis is a zoonotic infection and endemic in Iran. Due to the serological cross-reactivity (of sera) with other parasitic infection, diagnosis of hydatid cyst is considered to be problematic. In this regard, application of recombinant antigens improves serological diagnosis for human hydatidosis. Here, we present an ELISA test based on B8/2 recombinant antigen of Echinococcus granulosus with particular regard to its capability to diagnose human hydatidosis. The synthesized E. granulosus B8/2 (EgB8/2) gene was sub-cloned into pET28b (+) plasmid. Nde1 and Hind3 restriction enzymes were used to confirm the recombinant plasmid extraction. Cloning was verified by colony PCR, digestion enzymes, and sequence determination methods. To express rtEgB8/2, strains of Escherichia coli BL21 (DE3) pLysS and Rosetta (DE3) were induced with isopropyl β-D-1-thiogalactopyranoside (IPTG). A Ni-NTA column was used for purification, and the expressed protein was analyzed by SDS-PAGE as well as western blotting. ELISA test was used to identify the antigenicity of produced protein. The presence of EgB8/2 gene fragment in the recombinant plasmid was confirmed. SDS-PAGE showed that the BL21 (DE3) pLysS strain had the highest level of expression and a protein band of 11 kDa was observed in induced bacteria. Western blotting approved the purity of rtEgB8/2 protein, and ELISA test measured sensitivity and specificity as 95% and 97.5%, respectively. E. granulosus metacestode contains a high amount of antigen B protein. These results confirm the reproducibility of high-quality rtEgB8/2 recombinant antigen as a reliable candidate in serological test.

The aim of this study is to explore the potential neuroprotective effects of Ginkgolide B (GB), a main terpene lactone and active component in Ginkgo biloba, in hypoxia-induced neuronal damage, and to further investigate its possible mechanisms. 54 Sprague-Dawley rats were randomly divided into three groups: the untreated control group (n=18); the hypoxia group (n=18; exposed to 6000 m simulated plateau altitude for six days); and the GB group (n=18; intragastric administration of 12 mg/kg GB three days prior to rapid adaption to 6000 m and on the first two days of hypoxia). After hypoxia exposure for six days, we dissected out the brain hippocampi and performed hematoxylin and eosin staining, Nissl staining, and TUNEL staining. Homogenates of the hippocampi were used to test the oxidative stress indices including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and catalase. Bax and caspase-3 expression in the hippocampal tissue was measured using qRT-PCR. Treatment with GB before exposure to hypoxia could protect neural cells and increase the number of Nissl bodies. TUNEL and qRT-PCR results demonstrated that GB treatment could decrease apoptotic cells in different areas of the hippocampus. Antioxidant defense systems such as SOD, GSH, and catalase were decreased (P<0.05), and the concentration of MDA was reduced significantly in the hippocampi of rats of the GB group (P<0.05). GB could alleviate hypoxia-induced neuronal damage in rat hippocampus by inhibiting oxidative stress and apoptosis.

Because leishmaniasis is related to the impaired functioning of T-cells, the use of an immunomodulator can increase the efficacy of antileishmanial therapy in visceral leishmaniasis. In this study, we used shark cartilage extract with artemisinin and glucantime against visceral leishmaniasis in BALB/c mice, and evaluated the synergistic therapeutic effect. The culturing method and quantitative real-time PCR by using the kDNA gene was used to detect parasite loads in the spleen and liver. INF-γ and IL-4 cytokine levels and survival rates were assayed. The drug therapy with target drugs reduced parasite burden in the spleen and liver significantly. Although parasite burden was lower in the artemisinin treated group than in the glucantime treated group (P<0.05). The mice survival rate records, throughout the experimental period, showed highly significant survival rates in the test groups compared to the control group (P<0.001). The results of cytokine assay in mice treated with glucantime-shark cartilage extract combination indicated significant increases of IFNγ and IL-4 (P<0.05). Although the increase of IFNγ was more notable than IL-4. The synergistic therapeutic effect is shown in all groups except in the group treated with shark cartilage extract-artemisinin combination. The IFN-γ in glucantime-shark cartilage extract combination treated group was higher than in other groups (P<0.05). The survival rate in this group was more than in other groups too (P<0.05). Combination therapy with shark cartilage extract as an immunomodulator can increase antileishmanial effects of antimony drugs in VL treatment.

The main goal of the current research was to examine the effects of Berberine (BBR) on apoptotic signaling and hippocampal oxidative stress induced by common carotid artery occlusion. Chronic cerebral hypoperfusion (CCH) model was created by occluding the two common carotid arteries (two-vessel occlusion [2VO]) permanently. BBR (50 and 100 mg/kg/daily) was intra-gastrically administered to ischemic rats. Neuronal survival was evaluated by Nissl staining. The levels of malondialdehyde (MDA) and antioxidant enzymes, including catalase (CAT) and superoxide dismutase (SOD), along with the activities of caspase 3 were estimated in the hippocampus 2 month after treating the rats with 2VO. According to findings of the present research, the BBR therapy inhibited the neuro-degeneration of hippocampus. BBR also significantly decreased the amount of MDA and activity of caspase 3 in the hippocampus. Furthermore, the administration of BBR alleviated the lowered activities of SOD and CAT after 2VO surgery. The antioxidant and antiapoptotic properties of BBR might play important roles in improving functional outcomes and might have significant neuroprotective effects on the CCH damage.

Tanshinone IIA (T. IIA), one of the most pharmacologically active components extracted from Salviae miltiorrhiza, has anti-inflammatory and antioxidant features. The aim of the present study is to investigate the benefit of T. IIA on asthma using a murine model of asthma induced by ovalbumin (OVA). Male BALB/c mice were used in the present study. The mice were sensitized by OVA intraperitoneal injection on days 0 and 14, and received aerosolized OVA challenge for 30 min daily on days 21-23 Results T. T. IIA (10 mg/kg twice daily) intraperitoneal injection was performed on days 18-23. Treatment of T. IIA reduced the levels of interleukin (IL)-4, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF) (P T. IIA inhibits OVA-induced airway inflammation and hyperresponsiveness. T. IIA is a potential therapeutic agent for asthma.

Amyloid β plaques, in Alzheimer’s disease, are deposits in different areas of the brain such as prefrontal cortex, molecular layer of the cerebellum, and the hippocampal formation. Amyloid β aggregates lead to the release of cytochrome c and finally neuronal cell death in brain tissue. hCG has critical roles in brain development, neuron differentiation, and function. Therefore, we investigated the effect of hCG on the density of the congophilic Aβ plaque and cytochrome c-ir neurons in the hippocampus, prefrontal cortex, and cerebellum of Streptozotocin (STZ)-treated rats. Alzheimer model in rats (except the control group) was induced by streptozotocin (3 mg/kg, Intracerebroventricularly (ICV)). Experimental group rats received streptozotocin and then different doses of hCG (50, 100, and 200 IU, intraperitoneally) for 3 days. 48 hr after last drug injection and after histological processing, the brain sections were stained by congo red for congophilic amyloid β plaques and cytochrome c in the hippocampus, prefrontal cortex, and cerebellum were immunohistochemically stained. Density of congophilic Aβ plaques and cytochrome c-immunoreactive neurons was significantly higher in ICV STZ treated rats than controls. Treatment with three doses of hCG significantly decreased the density of congophilic Aβ plaques and cytochrome c-immunoreactive neurons in the rat hippocampus, prefrontal cortex, and cerebellum in ICV STZ-treated rats (P<0.05). hCG can be useful in AD patients to prevent the congophilic Aβ plaque formation and decrease cytochrome c-immunoreactive neuron density in the brain.

The prognosis of osteoporosis is very poor, and it is very important to identify a biomarker for prevention of osteoporosis. In this study, we aimed to identify candidate markers in osteoporosis and to investigate the role of candidate markers in osteogenic differentiation. Using Weighted Gene Co-Expression Network analysis, we identified three hub genes might associate with osteoporosis. The mRNA expression of hub genes in osteoblasts from osteoporosis patients or healthy donor was detected by qRT-PCR. Using siRNA and overexpression, we investigated the role of hub gene BRCC3 in osteogenic differentiation by alkaline phosphatase staining and Alizarin red staining. Moreover, the role of β-catenin signaling in the osteogenic differentiation was detected by using β-catenin signaling inhibitor XAV939. We identified three hub genes that might associate with osteoporosis including BRCC3, UBE2N, and UBE2K. UBE2N mRNA and UBE2K mRNA were not changed in osteoblasts isolated from osteoporosis patients, compared with healthy donors, whereas BRCC3 mRNA was significantly increased. Depletion of BRCC3 promoted the activation of alkaline phosphatase and formation of calcified nodules in osteoblasts isolated from osteoporosis patients and up-regulated β-catenin expression. XAV939 reversed the BRCC3 siRNA-induced osteogenic differentiation. Additionally, inhibited osteogenic differentiation was also observed after BACC3 overexpression, and this was accompanied by decreased β-catenin expression. BRCC3 is an important regulator for osteogenic differentiation of osteoblasts through β-catenin signaling, and it might be a promising target for osteoporosis treatment.

Cisplatin is an effective antineoplastic agent; its clinical utility, however, is limited by a few salient toxic side effects like nephrotoxicity. This study aimed to determine the potential protective effects of tangeretin, a citrus-derived flavonoid, against renal tubular cell injury in cisplatin-induced renal toxicity of rats. Tangeretin was injected intraperitoneally at 2.5 and 5 mg/kg doses for 10 days, and a single dose of cisplatin (8 mg/kg) was injected on the 7th day. Tests of kidney function and tubular injury in renal tissues and urine together with oxidative stress and inflammation markers were examined. Tangeretin ameliorated cisplatin-induced elevations in serum creatinine, BUN, and histopathologic changes. It also attenuated kidney oxidative stress elicited by cisplatin as demonstrated by reduced MDA and increased GSH, CAT, and SOD activities, elevated Nrf2 expression and protein levels of its downstream effectors, HO-1 and NQO-1. Tangeretin further alleviated inflammation evoked by cisplatin as indicated by reduced NF-κB p65 subunit phosphorylation with a simultaneous decrement in its downstream effectors IL-1β and TNF-α expression and protein levels. Moreover, it declined caspase-3 protein levels and TUNEL positive cells in the kidneys, the markers of apoptosis and DNA fragmentation, thus improving renal endurance. Additionally, tangeretin mitigated renal levels of KIM-1 and NGAL, as well as urinary cystatin C and β2-microglobulin concentrations, the markers of renal tubular injury. Collectively, these data signify the binary profit of tangeretin: enhancement of renal protective mechanisms against cisplatin and attenuation of renal tubular cell injuries induced by the agent.

This study was conducted to evaluate the cerebroprotective effect of methanolic leaf extract of Punica granatum (MePG) in Wistar rats. The MePG was initially assessed for in vitro antioxidant activity, and later evaluated on LPS-induced RAW 264.7 cell line assay. Finally, the MePG was evaluated against ischemia-reperfusion (I/R) induced brain injury in Wistar rats. In DPPH, FRAP and ORAC assays, the MePG has exhibited potent antioxidant activity. Further, the MePG has significantly inhibited the generation of nitrite, ROS and TNF-α in LPS-induced RAW 264.7 cell lines. Besides, global ischemia followed by reperfusion caused significant changes in the neurological and behavioral functions in I/R control animals compared to sham control. Additionally, in the I/R control group there was a substantial decrease in the catalase and superoxide dismutase activities; Likewise, reduced glutathione levels reduced and lipid peroxidation levels enhanced significantly. Also, pro-inflammatory cytokines such as TNF-α, IL-6, and ICAM-I were increased and the levels of IL-10 was decreased significantly. Furthermore, the I/R insult caused increase in brain volume and cerebral infarct formation. Similarly, histopathology of the brain tissue revealed hallmarks like necrosis, leukocyte infiltration, cerebral edema and vascular congestion in I/R control. Notably, MePG (200 and 400 mg/kg) pretreatment for 7 days, has attenuated all the I/R-persuaded pathological changes compared to I/R control. In addition, the LC-MS/MS analysis showed presence of acteoside, apigenin, gallic acid, gossypin, pentagalloyl glucose, quercetin, and rutin as major ingredients in the MePG. These findings suggest that the MePG possesses significant cerebroprotective activity.

Diabetes can gradually cause damage to the function and structure of male gonads. This survey was conducted to investigate the effect of troxerutin on hormonal changes, serum oxidative stress indices, and testicular function and structure in prepubertal diabetic rats.

Fifty prepubertal (6 weeks old) male Wistar rats were divided into five groups including Control, Troxerutin, Diabetic, Diabetic+Troxerutin, and Diabetic+Insulin. Type I diabetes was induced by 55 mg/kg of streptozotocin intraperitoneally. The groups were treated with 150 mg/kg/day troxerutin via oral gavage or 4-6 IU/day insulin via subcutaneous injection for 4 consecutive weeks. Blood sugar (BS) and serum levels of insulin, FSH, LH, testosterone, glutathione peroxidase (GPX), superoxide dismutase (SOD), malondialdehyde (MDA), and total antioxidant capacity (TAC) were analyzed. Testis and epididymis were removed for histopathologic study and analysis of sperm parameters.

Troxerutin significantly reduced the BS in the diabetic group similar to insulin but could not affect insulin, FSH, or LH significantly. Troxerutin caused a significant increase in testosterone and GPX but had no significant effect on serum MDA, TAC, and SOD levels. In addition, troxerutin had a better effect than insulin on diabetes-induced testicular structural damage. Sperm analysis results also revealed that troxerutin and insulin could improve sperm number, motility, and viability in diabetic rats.

According to these results, it can be derived that administration of troxerutin is a suitable protective strategy for side effects of diabetes in testis of prepubertal diabetic male rats.

To investigate the effect of cocoa on orthodontic tooth movement (OTM) rate, osteoprotegerin (OPG), and receptor activator of nuclear factor κ β ligand (RANKL) levels after OTM. A total of 24 Sprague-Dawley rats were included in the study. They were equally divided into two groups: cocoa and control. The upper incisors of all rats were subjected to 35 cN orthodontic force and moved distally with a stainless steel 3-spin coil spring. During OTM, the cocoa group was given 4.8 g of unsweetened cocoa once a day. At 4 subsequent time points (0, 1, 7, and 14 days), the OTM rate was determined by measuring the distance between the mesial tips using a digital caliper, while OPG and RANKL levels were examined based on their gingival crevicular fluid through specific enzyme-linked immunosorbent assay (ELISA). Data gathered were analyzed through independent t-test (P<0.05). The OTM rate of the cocoa group was significantly higher than that of the control group on days 1, 7, and 14 (P<0.05). ELISA analysis revealed that the OPG level was significantly lower on day 14. Furthermore, the RANKL level was significantly higher on days 0, 1, and 7 for the cocoa group compared with the control group (P<0.05). These results indicate that cocoa has the potential effect to modulate the OTM rate by inducing osteoclastogenesis, which suppresses the OPG level and stimulates the RANKL level, in rats.

Escherichia coli strains are common pathogens that can cause urinary tract infections (UTI). This study aimed to assess E. coli phylogroups and virulence types in male and female UTI patients. In the present study, 160 uropathogenic E. coli (UPEC) isolates (from both sexes) were assigned to phylogroups/types and some extraintestinal virulence factors were detected within them by multiplex-PCR. The isolates from women and men were predominantly distributed within phylogroup B2 and D, respectively. The presence of D2 phylotype was higher in men isolates than women, significantly (P=0.045). In male isolates papEF and sfa/focDE are more prevalent in B2 group than D, significantly (P=0.048; P=0.035). The prevalence of hly in B2 group is significantly higher than D (P=0.034) in female isolates. This study highlighted different features of E. coli genotypes from phylogenetic and virulence point of view implicated in UTI’s in both human genders.