Screening and introduction of key cell cycle microRNAs deregulated in colorectal cancer by integrated bioinformatics analysis

Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men worldwide. Impaired cell cycle regulation leads to many cancers and is also approved in CRC. Therefore, cell cycle regulation is a critical therapeutic target for CRC. Furthermore, miRNAs have been discovered as regulators in a variety of cancer-related pathways. This study is designed to investigate how miRNAs and mRNAs interact to regulate the cell cycle in CRC patients. Utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Expression Omnibus (GEO), and Therapeutic Target Database (TTD), cell cycle-associated genes were identified and evaluated. Seven of the 22 differentially expressed genes (DEGs) implicated in the cell cycle in three GSEs (GSE24514, GSE10950, and GSE74604) were identified as potential therapeutic targets. Then, using PyRx software, we performed docking proteins with selected drugs. The results demonstrated that these drugs are appropriate molecules for targeting cell cycle DEGs. Tarbase, miRTarbase, miRDIP, and miRCancer databases were used to find miRNAs that target the indicated genes. The ability of these six miRNAs to impact the cell cycle in colorectal cancer may be concluded. These miRNAs were found to be downregulated in SW480 cells when compared to the normal tissue. Our data imply that a precise selection of bioinformatics tools can facilitate the identification of miRNAs that impact mRNA translation at different stages of the cell cycle. The candidates can be investigated more as targets for cell cycle arrest in cancers.     

In vitro effects of clomiphene citrate on sperm parameters and fertilisation rate in male NMRI mice

Clomiphene citrate (CC), as a medication in male infertility, improves the sperm parameters in oral consumption but various detrimental side effects have been reported including testicular tumours, gynaecomastia, skin allergic reactions and ocular symptoms. Therefore, this study was designed to evaluate the in vitro effects of CC on sperm parameters and fertilisation rate in IVF protocol. Sperm samples of NMRI adult mice were divided into six groups: group 1 received no treatment (control group), while groups of 2, 3, 4, 5 and 6 (experimental groups) were incubated with the doses of 0.001, 0.01, 0.1, 1 and 10 µg/ml of CC in culture medium respectively. Sperm parameters (viability, morphology and motility), DNA fragmentation levels and fertilisation rate in IVF were evaluated. The results demonstrated that the doses of 0.1 µg/ml (p = .000007 for viability and p = .00006 for fertilisation rate) and 1 µg/ml (p = .032 for viability and p = .005 for fertilisation rate) CC cause a significant improvements; also, the dose of 0.1 µg/ml CC found effective on sperm motility (p = .0003). In the field of IVF, the application of 0.1 and 1 µg/ml of CC in the culture medium may improve the sperm parameters in IVF protocol with no side effects.     

Comparing the long-term retention of a physiology course for medical students with the traditional and problem-based learning

The rapid improvements in medical sciences and the ever-increasing related data, however, require novel methods of instruction. One such method, which has been given less than due attention in Iran, is problem-based learning (PBL). In this study, we aimed to evaluate the impact of study skills and the PBL methods on short and long-term retention of information provided for medical students in the course of respiratory physiology and compare it with traditional learning method. In this study, 39 medical students from Medical School of Kerman University of Medical Sciences, Kerman, Iran (2006–2010) were enrolled in the study and allocated randomly in three equal groups (13 in each group). All groups underwent a pre-test to be assessed for their basic information regarding respiratory physiology. Two groups were instructed using the traditional method, and one group used PBL. Among the two groups of the traditional method, one was instructed about study skills and the other was not. Once the PBL group took the study skill workshop, they were aided by tutors for their education. In the final term test, those students who had learned study skills and were instructed with the traditional method scored higher compared to other groups (p < 0.05). However, in the 1 year (p < 0.05) and 4 year (p < 0.01) interval examinations, the PBL group achieved significantly higher scores. Despite the fact that PBL had no positive effect on the final term exam of our students, it yielded a more profound and retained understanding of the subject course. Moreover, considering the positive effect of study skills on long-term student scores, we recommend students to receive instructions regarding the appropriate study skills when initiated into universities.     

Endovenous laser ablation of the great saphenous vein versus high ligation: long-term results

Endovenous laser therapy (EVLT) for greater saphenous vein (GSV) insufficiency is a relatively new method of treatment only recently made available in Iran. This is the first long-term randomized trial comparing EVLT with high ligation of saphenous vein (HLS) in the Iranian population. Sixty-five patients met the inclusion criteria and were divided into homogenous treatment groups of EVLT (n?=?30) or HLS (n?=?35). Clinical severity, etiology, anatomy, pathophysiology (CEAP) classification and Aberdeen Varicose Vein Symptom Severity Scores (AVSS) were used to determine disease severity and symptoms before and after the procedure in both groups. Outcome was measured by the rate of recurrence as shown in Doppler ultrasonography evaluation. Follow-up was conducted 1 week and 3, 6, 12, and 18 months after the intervention. The occlusion rate of GSV was similar in both groups (93.6 % for EVLT, 88.3 for HLS) at 18 months of follow-up. The median CEAP score showed a dramatic decrease in both groups after 1 week which was sustained for the rest of the study. The Aberdeen Varicose Vein Symptom Severity score was significantly lower in the EVLT group at 12 and 18 months of follow-up. There was no significant difference in patient satisfaction in both groups. Our findings show that EVLT may offer a better long-term relief of symptoms. This, alongside its better cosmetic outcome, and less invasive anesthesia requirements may make it the favorable choice for treatment of GSV insufficiency.     

The effect of estrogen on serum nitric oxide concentrations in normotensive and DOCA Salt hypertensive ovariectomized rats

BACKGROUND: Cardiovascular disease (CVD) is less prevalent in premenopausal women and women receiving estrogen replacement therapy (ERT) than in postmenopausal women or men. It proposed that the cardiovascular effects of estrogen are mediated, at least in part, through the ability of estrogen to increase nitric oxide (NO) synthesis. This study investigated the effect of estrogen on serum NO concentrations in normotensive and deoxycorticostrone acetate (DOCA) Salt hypertensive ovariectomized rats. METHODS: Forty-eight female rats were ovariectomized and randomly divided into six groups. Hypertension was induced by DOCA Salt method. DOCA was injected 30 mg/kg of body weight subcutaneously, twice a week with NaCl 1% instead of tap water for drinking throughout the treatment period. Estradiol valerate (Es) was injected i.m. once a week. The groups were as follows: (2) DOCA (4 weeks) and DOCA+Es (6 weeks), (22) DOCA (10 weeks), (222) normal saline (N/S) (4 weeks)+Es (6 weeks), (2V) N/S (10 weeks), (V) DOCA (4 weeks), and (V2) N/S (4 weeks). Serum NO concentrations were measured in groups 1, 3 and 4 before and after treatment. Other groups were used as control. RESULTS: Results showed that in normotensive animals, serum NO concentrations were increased after estrogen treatment significantly (90.20 +/- 18.67 vs. 19.11 +/- 1.78 micromol/l) (p < 0.05). Also, estrogen increased serum NO concentrations in DOCA Salt hypertensive rats (73.54 +/- 22.55 vs. 36.94 +/- 10.73 micromol/l) (p = 0.06). CONCLUSION: Estrogen can increase serum NO concentrations in normotensive and DOCA Salt hypertensive animals and it may be important in cardiovascular effects of estrogen.     

Human leukocyte antigen profile in the Zaboli ethnic group living in the South-East region of Iran

The human leukocyte antigen has become a key component in investigating the genetic relationships between populations. The aim of this study was to determine the genetic diversity of HLA class I and II alleles among Zaboli ethnic group of South-east Iran to establish a database for further investigations on ancestry and the genetic factors contributing to complex diseases in this region.Unrelated individuals from the Southeast geographic location throughout Iran were serologically typed using standard microcytotoxicity assays with commercial and local trays. The ethnic background of each individual was self-defined. HLA profiles were determined in 41 Zaboli populations. The most frequent class I alleles of the Zaboli ethnic group being the following: HLA-A1 (34.1%), -A2 (58.5%), -A11 (29.3%), -A24 (23.9%), -B5 (70.7%), -B16 (26.8%), and -Cw4 (24.4%). The class II alleles more frequently observed in this group were HLA-DR1 (26.8%), -DR2 (26.8%), -DR3 (31.7%), -DR4 (29.3%), -DR7 (24.4%), -DR8 (22%), -DR11 (48.8%), -DRw52 (73.2%), -DRw53 (53.7%), -DQ1 (53.7%), -DQ2 (31.7%), and -DQ3 (29.3%). This report utilized a first study of HLA class I and II typed individuals, from widely dispersed areas of Iran. This will help in studies related to disease associations and cadaver organ allocation programmes.     

The study of type 1 allergy prevalence among people of South-East of iran by skin prick test using common allergens

The prevalence of allergic disorders has increased markedly throughout the world over the past three decades. It seems probable that the increased prevalence is real because longitudinal studies have shown a rapid exponential increase in allergic disorders. In order to determine the prevalence of type 1 allergy in patients with allergic disorders in Sistan-Blouchestan province, in the Southeast of Iran, patients referred to Immunology and Allergy Medical Center of Khatam Hospital during a 7-year period were studied. One thousand two hundred and eighty-six patients (554 males and 732 females), aged 2-79 years, had allergic disorders. The most frequent allergic disease was rhinitis, seen in 959 patients ( 74.57%). Also, 939 patients had a history of sinusitis (73.02%). Among the skin prick test(SPT)-positive patients, a positive prick test reaction to the house dust mites (89.74%), feathers (70.29%), and Aspergillus (65.08%) was most common, followed by Alternaria (57.39%), Cladosporium (47.12%), grasses (43.39%), trees (41.29%), Penicillium (39.19%), fruits (38.41%), and weeds (32.50%). Also, 30.33% of the subjects were sensitized to Hen's egg in the prick test, walnut (29.16%), cow's milk (21.46%), beef meat (19.21%), and hazel-nut (15.32%) accounting for other positive reactions. The prevalence of SPT-positive to common allergens is high among Iranian patients with allergic disorders. So, it should be recognized in the diagnosis of allergic diseases as well as in allergen-reduction programs.     

Role of peroxisome proliferator-activated receptor β agonist on angiogenesis in hindlimb ischemic diabetic rats

IntroductionStudies indicated that PPARβ agonists play a role in modulation of angiogenesis. In this study, we evaluated the effect of specific PPARβ agonist, GW0742, on angiogenesis and serum vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), and nitrite concentrations in hindlimb ischemia in normal and diabetic rats.MethodsHindlimb ischemic rats were divided into four groups: control, diabetic, control, and diabetic treated with GW0742 (n = 7 each). Diabetes was induced by injection of streptozotocin (55 mg/kg, ip). GW0742 was injected 1 day after surgery (1 mg/kg, sc). After 21 days, blood samples were taken, and gastrocnemius muscles were harvested for immunohistochemistry.ResultsGW0742 significantly increased serum nitrite and VEGFR-2 concentrations and VEGF-to-VEGFR-2 ratio in control and diabetic rats. Capillary density was lower in diabetic animals compared to the control, and GW0742 significantly restored the capillary density in the control and diabetic hindlimb ischemic rats.ConclusionPPARβ agonists restore skeletal muscle angiogenesis and can be considered for prevention and/or treatment of peripheral vascular complications in diabetic subjects.     

Effect of acute and chronic hypertension on short- and long-term spatial and avoidance memory in male rats

It has been demonstrated that hypertension can lead to coronary heart disease, heart failure, stroke, and memory loss. In this study we investigated the effect of acute and chronic hypertension on the avoidance and spatial learning and memory in rats. The forty male rats were divided into acute hypertensive, chronic hypertensive and control for each group rats. Hypertension was induced by Deoxy Corticosterone Acetate (DOCA)-salt method. DOCA was injected 30 mg/kg of body weight subcutaneously, twice a week. These rats received NaCl 1% instead of tap water for drinking throughout the experiment. The control group received normal saline injection with usual drinking water. Spatial learning and memory was investigated by Morris water maze test and passive avoidance learning by Shuttle box test in the rats after hypertension induction. Results showed that acute hypertension impaired short-term memory in passive avoidance learning. However, acute and chronic hypertension did not affect spatial learning and memory. These data suggest that simple uncomplicated hypertension does not remarkably alter cognition.