Iranian Journal of Basic Medical Sciences
Year:2018 | Volume:21 | Issue:11|Papers Count:15

Saffron petal is the main by-product of saffron processing which produced at high level but it is not applied and thrown out. Saffron petal is containing of several compounds such as mineral agents, anthocyanins, flavonoids, glycosides, alkaloids and kaempferol. As saffron petal is cheaper and produces in large amounts compared to saffron stigma, so, it can be considered as an appropriate source for different purposes. In this review different pharmacological properties of saffron petal such as antibacterial, antispasmodic, immunomodulatory, antitussive, antidepressant, antinociceptive, hepatoprotective, renoprotective, antihypertensive, antidiabetic and antioxidant activity have been introduced. According to these properties, saffron petal can be used as an alternative or supplementary medicine in some diseases.

Objective(s): Phage therapy is a potential alternative treatment for infections caused by Acinetobacter baumannii, a significant nosocomial pathogen, which has evolved resistance to almost all conventional antimicrobial drugs in poor hygiene and conflicts areas such as Iraq. Materials and Methods: Bacteriophages were isolated to highly resistant isolates of A. baumannii to form therapeutic phage cocktail, and to extract and evaluate native endolysin activity. Bacterial samples were collected in Al-Imamein Al-kadhimein Medical City Hospital. Phages were isolated from different regions in Baghdad city including (soil, sewage, irrigation channels). Phage endolysin was extracted from highly lytic phages that produced halo-like appearance around inhibition zone. Results: Up to 23 isolates of extensive-and pan-drug resistant (XDR, PDR) A. baumannii were isolated from patients with various infections, and 136 lytic phages specific to A. baumannii were isolated. Each bacterial isolate was sensitive to at least one lytic phage. Accordingly, a phage cocktail was formulated which remarkably minimized bacterial resistance to lysis by phages when compared to individual lytic phages. And, the phage cocktail succeeded in treating and saving life of all bacteremic mice with A. baumannii versus the non-treated group. In addition, the endolysin native activity to A. baumannii was evaluated in this study; endolysin revealed a potent antibacterial activity (> 1 log) reduction of bacterial density in just one hour of endolysin treatment. Conclusion: The phage therapy assessed in this study showed an ability to efficiently solve the problems of “ superbug” bacteria by lysing effectively most XDR, PDR bacteria in vitro and in vivo. And, phage cocktail was shown to be superior over single-phage preparations in treating A. baumannii with much less resistance rate to therapeutic phages. Furthermore, intrinsic activity of native endolysin revealed promising results to tackling superbug pathogens.

Objective(s): Failed fertilization after intra-cytoplasmic sperm injection (ICSI) is mainly attributed to failed oocyte activation and can be overcome by artificial oocyte activation (AOA). The present study aims to compare in vitro outcomes of ICSI following two different assisted oocyte activation chemical procedures (SrCl2 and Ionomycin) in sibling oocytes of ICSI candidates. Materials and Methods: From March 2015 until February 2016, 105 infertile men with 99– 100% abnormal sperm morphology, irrespective of sperm motility, concentration, or origin (semen or testicular) were included in this study. Out of these, 66 couples accepted to be included in the study group (Ionomycin/ SrCl2) and 39 couples requested routine AOA procedure (Ionomycin) as external control group. Primary outcomes of this study (fertilization, embryo quality, and post-implantation development) were compared between these groups. Results: Significantly higher oocyte activation (67. 90± 3. 6% vs. 51. 16± 3. 6%, P=0. 004) and fertilization (65. 23± 3. 63% vs. 49. 65± 3. 63%, P=0. 008) rates were observed in sibling oocytes treated with Ionomycin in comparison to the SrCl2 sibling group. Percentage of top quality embryos was insignificantly higher in SrCl2 groups compared to the Ionomycin group (29. 90± 4. 27 vs. 20. 65± 4. 05%, P=0. 26). Conclusion: Ionomycin may be superior to SrCl2 for inducing oocyte activation. However, SrCl2 may be a more efficient means to support the development of better quality embryos following ICSI.

Objective(s): In this study, potential protective effects of Bortezomib (Bort), as a proteasome inhibitor, were investigated on the uterus of ovariectomized rats by histological, morphometric and immunohistochemical methods. Materials and Methods: In this study, 18 Sprague dawley strain female rats (12 weeks old, 250-300 g body weight) were used. Animals in the control group (Cont, n=6) were not exposed to any treatment. Ovariectomy was performed on the experimental groups. They (n=12) were divided into ovariectomy (Ovt, n=6) and Bortezomib (Bort, n=6) subgroups. Twelve weeks later, the rats were perfused. Then, uterine tissues were removed and examined by morphometrical, and light and electron microscopy methods. In addition, immunoreactivity of nuclear factor-kappa (NF-κ B) was evaluated. Results: Morphometric and histopathological evaluations showed that Bort was effective in the uterus and protects the layer structures and the cells. Conclusion: In the light of these findings, we suggest that for proteasome inhibitor particularly Bort is thought to be useful through proteasome inhibition and NF-κ B pathway

Objective(s): The use of a co-culture of islets with mesenchymal stromal cells (MSCs) is a promising therapy in islet transplantation to revert hyperglycaemia, but the resulting insulin-producing cells (IPCs) express low levels of pancreas endocrine developmental genes. This study aims to investigate the morphochronology of a co-culture of islets with MSCs from injured adult pancreata, and characterize pancreatic duodenal homeobox protein-1 (Pdx1), neurogenin-3 (Ngn3) and insulin protein expressions to establish the fate of their interaction. Materials and Methods: Islets and MSCs were isolated from sham operated control (SOC) and ductligated (PPDL) pancreata. Islets from SOC or PPDL tissues were cultured with or without MSCs in RPMI1640, supplemented by 1% Penicillin-Streptomycin, and maintained at 37 ° C± 1 ° C at 95% relative humidity and 95% /5% air/CO2. Pdx1, Ngn3 and insulin expressions were determined by immunohistochemistry and islet morphochronological changes were assessed. Results: Pdx1 was expressed in all islet-cell cultures with or without MSCs. Pdx1+ islet cells were significantly increased in the presence of MSCs compared to the islet culture without MSCs. Similarly, Ngn3 was highly expressed in all cultures with MSCs from both SOC and PPDL tissues and the expression was prolonged in cultures using PPDL tissues before it was down-regulated, thereby, extending the period of Ngn3+ cell expansion and differentiation into mature functional islets. Conclusion: In vitro, MSCs maintain a pool of Ngn3+ that contributes to insulin production from mature beta cells but the activation of insulin production from non-beta cells may not be induced by direct signals from MSCs.

Objective(s): Photo-thermal therapy (PTT) is a therapeutic method in which photon energy is converted into heat to induce hyperthermia in malignant tumor cells. In this method, energy conversion is performed by nanoparticles (NPs) to enhance induced heat efficacy. The low-cytotoxicity and high optical absorbance of NPs used in this technique are very important. In the present study, titanium dioxide (TiO2) NPs were used as agents for PTT. For increasing water dispersibility and biocompatibility, polyethylene glycol (PEG)-TiO2 NPs (PEGylated TiO2 NPs) were synthesized and the effect of these NPs on reducing melanoma tumor size after PTT was experimentally assessed. Materials and Methods: To improve the dispersibility of TiO2 NPs in water, PEG was used for wrapping the surface of TiO2 NPs. The formation of a thin layer of PEG around the TiO2 NPs was confirmed through thermo-gravimetric analysis and transmission electron microscopy techniques. Forty female cancerous mice were divided into four equal groups and received treatment with NPs and a laser diode (λ = 808 nm, P = 2 W & I = 2 W/cm2) for seven min once in the period of the treatment. Results: Compared to the mice receiving only the laser therapy, the average tumor size in the mice receiving TiO2-PEG NPs with laser excitation treatment sharply decreased. Conclusion: The results of animal studies showed that PEGylated TiO2 NPs were exceptionally potent in destroying solid tumors in the PTT technique.

Objective(s): As the most prevalent endocrine system malignancy, papillary thyroid carcinoma had a very fast rising incidence in recent years for unknown reasons besides the fact that the current methods in thyroid cancer diagnosis still hold some limitations. Therefore, the aim of this study was to improve the potential molecular markers for diagnosis of benign and malignant thyroid nodules to prevent unnecessary surgeries for benign tumors. Materials and Methods: In this study, 1H-NMR metabolomics platform was used to seek the discriminating serum metabolites in malignant papillary thyroid carcinoma (PTC) compared to benign multinodular goiter (MNG) and healthy subjects and also to better understand the disease mechanisms using bioinformatics analysis. Multivariate statistical analysis showed that PTC and MNG samples could be successfully discriminated in PCA and OPLS-DA score plots. Results: Significant metabolites that differentiated malignant and benign thyroid lesions included citrate, acetylcarnitine, glutamine, homoserine, glutathione, kynurenine, nicotinic acid, hippurate, tyrosine, tryptophan, β-alanine, and xanthine. The significant metabolites in the PTC group compared to healthy subjects also included scyllo-and myo-inositol, tryptophan, propionate, lactate, homocysteine, 3-methyl glutaric acid, asparagine, aspartate, choline, and acetamide. The metabolite sets enrichment analysis demonstrated that aspartate metabolism and urea cycle were the most important pathways in papillary thyroid cancer progression. Conclusion: The study results demonstrated that serum metabolic fingerprinting could serve as a viable method for differentiating various thyroid lesions and for proposing novel potential markers for thyroid cancers. Obviously, further studies are needed for the validation of the results.

Objective(s):-methyl-D-aspartate NMDA receptor (NMDAR) and aquaporin 4 (AQP4) are involved in the molecular cascade of edema after traumatic brain injury (TBI) and are potential targets of studies in pharmacology and medicine. However, their association and interactions are still unknown. Materials and Methods: We established a rat TBI model in this study. The cellular distribution patterns of AQP4 after inhibition of NMDAR were determined by Western blotting and immunoreactive staining. Furthermore, the regulation of NMDA receptor 1 by AQP4 was studied by injection of a viral vector targeting AQP4 by RNAi into the rat brain before TBI. Results: The results suggest that AQP4 protein expression increased significantly (P<0. 05) after TBI and was down-regulated by the NMDAR inhibitor MK801. This decrease could be partly reversed using the NMDAR agonist NMDA. This indicated that AQP4 mRNA levels and protein expression are regulated by the NMDA signaling pathway. By injection of AQP4 RNAi viral vector into the brain of TBI rat models, we found that the mRNA and protein levels of NMDAR decreased significantly (P<0. 05). This suggested that NMDAR is also regulated by AQP4. Conclusion: These data suggested that the inhibition of AQP4 down-regulates NMDAR expression, which might be one of the mechanisms involved in edema after TBI.

Objective(s): Among several cell sources, adult human neural stem/progenitor cells (hNS/PCs) have been considered outstanding cells for performing mechanistic studies in in vitro and in vivo models of neurological disorders as well as for potential utility in cell-based therapeutic approaches. Previous studies addressed the isolation and culture of hNS/PCs from human neocortical and hippocampal tissues. However, little data are available on hNS/PCs obtained from the adult human amygdala. Materials and Methods: The present study explored the capacity of the amygdala harvested from resected brain tissues of patients with medically refractory epilepsy to generate neurosphere-like bodies and motor neuron-like cells. Results: Although the proliferation process was slow, a considerable amount of cells was obtained after the 3rd passage. In addition, the cells could generate motor neuron-like cells under appropriate culture conditions. Conclusion: Isolation and culture of these cells enable us to improve our knowledge of the role of the amygdala in some neurological and psychological disorders and provide a novel source for therapeutic cell transplantation.

Objective(s): A growing body of evidence indicates that rhomboid domain containing 1 (RHBDD1) plays an important role in a variety of physiological and pathological processes, including tumorigenesis. We aimed to determine the function of RHBDD1 in breast cancer cells. Materials and Methods: In this study, we used the Oncomine™ database to determine the expression patterns of RHBDD1 in normal and breast cancer tissues. We performed lentiviral transfection of RHBDD1-specific small interfering RNA into the breast cancer cell lines ZR-75-30 and MDA-MB-231 in order to investigate the effects of RHBDD1 deficiency on breast cancer metastasis. Results: We found that knockdown of RHBDD1 inhibited breast cancer cell migration and invasion in vitro. Moreover, knockdown of RHBDD1 promoted epithelial– mesenchymal transition (EMT) by suppressing the expression of MPP2, MPP9, fibronectin 1, vimentin, SRY-box 2, zinc finger E-box binding homeobox 1, and snail family transcriptional repressor 1, and promoting the expression of cadherin 1. Additionally, knockdown of RHBDD1 inhibited the protein expression and phosphorylation of Akt. Conclusion: Our data indicate that RHBDD1 overexpression may promote breast cancer metastasis via the regulation of EMT, suggesting that RHBDD1 may be an important regulator of breast cancer metastasis.

Objective(s): Breast cancer remains a global challenge, and further chemopreventive therapies are still immediately required. Emerging evidence has revealed the potent anti-cancer effects of biguanides, Metformin (MET) and phenformin (PHE). Thus, to explore an efficient chemopreventive strategy for breast cancer, the antiproliferative effects of the combination of MET and PHE against breast cancer cells were assessed. Materials and Methods: Cytotoxicity of the drugs individually and in combination against T47D and MDAMB-231 breast cancer cells were assessed using MTT assay and the median-effect method was used to analyze the precise nature of the interaction between MET and PHE. Besides, the expression levels of hTERT after 48 hr drug exposure were determined using qRT-PCR. Results: Based on the cytotoxicity assay, both MET and PHE further inhibited the growth of MDAMB-231 cells compared with T47D cells. It was found that MET+PHE reduced the IC50s of MET and PHE in both cells drastically more than the single treatments in a synergistic manner. Importantly, MET+PHE showed higher antiproliferative effect with smaller IC50 values against MDA-MB-231 cells than against T47D cells. Real-time PCR results revealed that hTERT expression was significantly reduced in both breast cancer cell lines treated with MET+PHE than the single treatments. In comparison between two types of breast cancer cells, it was detected that MET+PHE could further decline hTERT expression in MDAMB-231cells than in T47D cells (P<0. 001). Conclusion: It is speculated that the combination of MET and PHE may be a promising and convenient approach to improve the efficiency of breast cancer treatment. speculated that the combination of MET and PHE may be a promising and convenient approach to improve the efficiency of breast cancer treatment.

Objective(s): Paeoniflorin (PF) has anti-oxidation, anti-inflammation, anti-apoptosis, and neuroprotection pharmacological effects against ischemic injury. The aim of the present study was to investigate the neuroprotection mechanisms of PF in cerebral ischemia-reperfusion injury rats. Materials and Methods: We established an animal model of cerebral infarct by occlusion of the middle cerebral artery for 15 min, followed by reperfusion, and PF was administered 24 hr later (20 mg/kg, intraperitoneally for 6 days) after reperfusion Results: Treatment with PF reduced the neurological deficit score, improved motor function, decreased cell counts of nicotinic acetylcholine receptor (nAChR) α 4β 2 immunoreactive cells, and increased cell counts of nAChR α 7. Furthermore, PF administration suppressed neuronal apoptosis and promoted neurogenesis. Conclusion: PF rescued neurological deficit and underlying mechanisms were inhibition of neurological apoptosis and inflammation by nAChRs.

Objective(s): Iranian crack (IC) is a heroin-based substance manifesting various pathologic side effects. Herein, we aimed to investigate the mechanism of IC-induced liver injuries in Wistar rats. Materials and Methods: Twenty male Wistar rats were randomly divided into two groups: control, and IC (0. 9 mg/kg/day/IP, for 30 days). Mitochondrial reactive oxygen species (ROS) production was measured by DCF fluorescence staining. The expression of tumor necrosis factor-alpha (TNF-α ), interleukin 1β (IL-1β ), and phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (c-JNK) were assessed by immunoblotting assay. The intensity of collagen fiber in the liver was also determined by Trichrome-Masson staining. Furthermore, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities were measured using colorimetric methods. Results: Our results showed that ROS production, p38 MAPK, c-JNK phosphorylation levels, and expression of TNF-α and IL-1β were significantly elevated in the liver tissue of IC group as compared to the control group. Moreover, collagen fiber and ALT activity were increased in the liver tissue of IC group compared to the control group. However, there was no statistically significant difference in the levels of ALP between two groups. In addition, there was a positive correlation between the intensity of collagen fiber and the ALT activity, and the levels of TNF-α and IL-1β and liver enzymes activities including ALP, ALT, and AST. Conclusion: Our findings revealed that IC-induced liver cells injury is partially mediated by MAPK stress kinases. Therefore, regular liver examination in substance abuse is strongly recommended.

Objective(s): Circular RNAs (circRNAs), a new class of non-coding RNAs, have emerged as important regulators during tumorigenesis. However, the functions of circRNAs have not been completely clarified in the progression of cancers. In our study, a novel circRNA hsa_circ_0109291 was investigated in oral squamous cell carcinoma (OSCC) tissues and cell lines. Materials and Methods: The expression profile of circRNAs in OSCC tumor tissues was performed by highthroughput sequencing. The CCK-8 wound healing and apoptosis assay were measured in OSCC cell lines after transfection with si-0109291 or si-NC. Results: We discovered that hsa_circ_0109291 was significantly increased in OSCC tissues and cell lines compared with their corresponding control group. Knockdown of hsa_circ_0109291 inhibited proliferation and migration of OSCC cell lines in vitro. In addition, inhibition of hsa_circ_0109291 dramatically induced apoptosis of OSCC cells. We further found that high hsa_circ_0109291 levels in OSCC patients resulted in a poorer prognosis than in patients with low hsa_circ_0109291 levels. Conclusion: These findings indicated that hsa_circ_0109291 correlated with the progression of OSCC and might be a new therapeutic target for the treatment of OSCC.

Objective(s): Crocetin, one of the main substances of saffron extract, has anti-cancer effects. Drug resistance proteins (e. g. MRP1 and MRP2) are important reasons for the failure of cancer therapy. We intended to investigate the efficacy of crocetin on MRP1 and MRP2 activity in human ovarian cisplatinresistant carcinoma cell line (A2780-RCIS). Materials and Methods: The cytotoxic effect of crocetin was evaluated by the MTT assay. The efficacy of crocetin on MRP1 and MRP2 expression at mRNA level was studied by real-time RT-PCR. The effect of crocetin on the activity of MRP transporters was determined by drug efflux assay. Results: Crocetin decreased cell proliferation in the A2780 (IC50: 183± 7 μ M) and A2780-RCIS (IC50: 316± 9 μ M). Crocetin decreased the expression level of MRP1 (22± 2 %) and MRP2 (48± 8 %) in A2780-RCIS and inhibited MRP pumps function directly in A2780 (44± 1 %) and A2780-RCIS (88± 10 %) and indirectly in A2780 (32± 2 %) and A2780-RCIS (48± 15 %) respectively. Conclusion: Our findings showed that crocetin could quench drug resistance through modulation of MRP transporters in the drug resistant human ovarian cancer cells.