Modulating Wnt/ß-Catenin Signaling Pathway on U251 and T98G Glioblastoma Cell Lines Using a Combination of Paclitaxel and Temozolomide, A Molecular Docking Simulations and Gene Expression Study.

One of the most lethal cancers, glioblastoma (GBM), affects 14.5% of all central nervous system (CNS) tumors. Patients diagnosed with GBM have a meager median overall survival (OS) of 15 months. Extensive genetic analysis has shown that many dysregulated pathways, including the Wnt/ß-catenin signaling system, contribute to the pathogenicity of GBM. Paclitaxel (PTX) and temozolomide (TMZ) are recognized to have therapeutic potential in several types of cancer, including GBM. This work aimed to examine the impact of PTX and TMZ on the human glioma cell lines U251 and T98G using molecular docking simulations and gene expression profiles in the Wnt/ß-catenin signaling pathway. Standard procedure for Molecular Docking simulation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay, and Flow Cytometry assay was used. Genes implicated in the Wnt/ß-catenin signaling pathway, including Dvl, Axin, APC, ß-catenin, and glycogen synthase kinase3-ß (GSK3ß), were subjected to real-time PCR. The estimated parameters for targets revealed that the average binding energy and inhibition constant (Ki) for the DVL, ß-Catenin, and GSK3ß, when targeted by PTX, were - 5.01 kcal/mol, - 5.4 kcal/mol, and - 9.06 kcal/mol, respectively. This energy range was - 6.34 kcal/mol for DVL, - 5.52 kcal/mol for ß-Catenin, and - 5.66 kcal/mol for GSK3ß as a result of TMZ's inhibitory actions. Gene expression analyses indicated that PTX and PTX/TMZ suppressed GSK3ß (p < 0.05). GSK3ß from the Wnt/ß-catenin signaling pathway was significantly targeted by PTX alone, and adding TMZ to PTX may improve the efficacy of glioblastoma treatment. In addition, the GSK3ß gene may help GBM therapy strategies as a potential PTX target.

The Effect Of Preoperative Gabapentin on Pain Severity After Posterior Urethral Surgery: A Randomized, Double-Blind, Placebo-Controlled Study.

PURPOSE: Prevention and treatment of urethroplastic postoperative pain is a major challenge in post-surgery care. gabapentin can treat postoperative pain by preventing excessive sensitivity to the central nervous system. we have tried to compare the effect of gabapentin with the placebo on reducing the pain associated with posterior urethroplasty in patients. MATERIAL AND METHOD: This prospective, randomized, double-blind study was scheduled in Shohad e Tajrish hospital where a single dose of Gabapentin was compared with placebo given to patients preoperatively. In this study,100 patients with posterior urethral stricture were included for surgery with 50 patients in each arms .All patients underwent posterior urethroplasty. After surgery, the pain level is assessed and evaluated by the visual analog scale in two hours,four hours, six hours,eight hours, twelve hours, and 24 hours after the operation. RESULT: In this study, there was a significant difference in the pain level that was evaluated by the visual analog scale in two hours, four hours, six hours, eight hours, twelve hours, and 24 hours after the surgery (p.value <0.001). We also found a significant decrease in morphine consumption in the gabapentin group vs the placebo group. (p.value <0.001) The post-surgery assessments showed significant lower adverse effects such as vomiting, nausea, drowsiness, and pruritus in the gabapentin group vs. placebo group. CONCLUSION: The consequences of this study revealed that gabapentin effective in controlling posterior urethroplasty postoperative pain, consumption of opioid, nausea, vomiting, drowsiness, and pruritus compared with the placebo group.

Oncogenic miRNAs and target therapies in colorectal cancer.

OncomiRNAs involved in human colorectal cancer (CRC) are capable of suppressing the expression of their targets via cleavage or translational arrest. Therefore, an improved understanding the functions of these oncomiRNAs and the molecular pathways in CRC development that they are involved in will assist in the manipulation of miRNAs, providing a novel therapeutic approach against CRC. In this review, we provide a particular perspective of miRNAs implicated in the progression of CRC. We describe an interaction network of CRC-associated miRNAs and their targets involved in tumor growth, proliferation, migration/invasion, epithelial-to-mesenchymal transition (EMT) formation, metastasis, and anticancer resistance. Additionally, the therapeutic potentials of these miRNAs in CRC are fully discussed. Thus, key oncogenic miRNAs involved in progression and metastasis of CRC (e.g., miR-181a/b, miR-135a/b, miR-150 and miR-150-5p, miR-155, miR-181b, miR-200 a/c, miR-22, miR-106a, hsa-miR-103a, hsa-miR-1827, miR-135b, miR-150 and miR-150-5p, miR-181b, and let-7f-5p) are considered in this review. Furthermore, proangiogenic and antiapoptotic miRNAs, their molecular regulatory networks, biological functions, and target genes are also discussed. An in-depth understanding of the molecular mechanisms underlying the regulation of miRNAs will increase the knowledge of miRNA regulatory function in the progression of CRC and promote the development of novel therapeutic measures.

Novel management of glioma by molecular therapies, a review article.

The most frequent type of brain tumors is Glioma which commonly appears initially in the neuroglia in the central nervous system. They grow steadily and generally do not outspread to neighboring tissue of the brain. By applying dominant remedial regimens, the patients would have negligible survival rates. Despite the achieved advances in conventional glioma therapy, it proved that a proper medication for glioma is not easily reachable. The glioma penetration nature and accumulate resistance considerably limit the remedial options. Superior explanation of the glioma complex pathobiology and characterization of biological proteogenomic may finally open new approaches for the outlining of extra artificial and impressive combination regimens. This aim could be achieved by exclusively outfitting advanced techniques of neuroimaging, terminating synthesis of DNA via genes that activated via prodrugs, experimental technique of gene therapy via conciliating genes of gliomagenesis, targeting miRNA-mRNA activity of oncogenic, applying stem cell therapy for combining inhibitors of Hedgehog-Gli, adaptive transmission of chimeric immunoreceptors T cells, incorporate inhibitors of regulators of the immune system with conventional remedial modalities and additionally using tumor cell lysates as sources of antigen for efficient evacuation of particular stem cells of tumor via cytotoxic T lymphocytes. Consequently, in this study the authors trying to survey the latest progressions related to the molecular procedures connected with the formation of glial tumors in addition to the radiation, surgery and chemotherapy limitations. Additionally, the novel strategies of molecular remedies and their procedure for the prosperous treatment of glioma will be discussed.

Studying the Prevalence of Medical Interventions in the Recipes.

BACKGROUND: Drug interaction is a term used to refer to unfavourable side effects caused by mixing or taking two or more drugs simultaneously. Although it is not possible to identify all drug interactions, awareness of therapeutic team of potential drug interactions, risk factors that enhance the possibility of these interactions and familiarity with mechanisms of drug interactions can help reduce real drug interactions. AIM: The present research seeks to study the frequency and intensity of possible interactions among various age groups and their correlation with doctor's speciality, time of drug prescription, patient's gender, etc. MATERIAL AND METHOD: This is observational, cross-sectional research conducted in spring and winter to study the prevalence of drug interactions among 6000 recipes belonging to 2 private and 2 public drug stores. The information associated with recipes was recorded, and drug interactions were studied based upon quick index of interactions using Up to Date software. Quick index of medical interactions is a response to data dealing with how drugs interact with one another. The risk factor is divided into groups A, B, C, D, and X according to this index with each one having its own definition. The data analysis was studied in terms of prevalence type of drug interactions and the possible correlation with other parameters. SPSS v.16 was used for statistical analysis. RESULTS: The average age of the patients was 42.07 ± 21.56 years. The frequency of male patients was 41.7%. An average number of 4.82 ± 1.91 drugs were prescribed for each patient and an average number of 1.95 ± 2.40 drugs had interaction with one another with levels C, D, and X having the following drug interaction levels: 1.60 ± 2.05, 0.275 ± 0.69, and 0.072 ± 0.31. No such interactions were observed in 31.1% (1846 cases) of recipes. The presence of drug interaction was statistically significant in terms of age, season, drug store and speciality of doctor (P-value < 0.05). The average number of interactions in the recipes issued by psychologists, cardiologists, rheumatologist, neurologists, and general practitioners was more, and this result was statistically significant (P-value < 0.05). CONCLUSION: Considering the results achieved in this research, we may conclude that the drug interactions in recipes exhibit a noticeable frequency with the highest frequency observed in level C influenced by factors such as age, season, class of drugs, and expertise of the doctor.

The relationship between components of metabolic syndrome and plasma level of sex hormone-binding globulin.

Plasma concentration of sex hormone-binding globulin (SHBG), as an androgen binding protein, is impressed by many physiological and environmental factors. Recent studies have shown that plasma level of SHBG is related to some components of metabolic syndrome (MetS); however, in contrast, few articles failed to show any associations between SHBG and MetS. So, this study was conducted to investigate the relationship between Components of Metabolic Syndrome and Plasma Level of Sex Hormone-Binding Globulin. In this study, after measuring the plasma level of SHBG in 84 individuals, the relation between MetS and the plasma level of SHBG was investigated. After evaluating the plasma level of SHBG and metabolic abnormalities in men and women, we investigated the factors which mentioned above in two groups including patients with and without MetS. Also, the metabolic abnormalities which evaluated in this study including plasma level of 25-hydroxyvitamin D, serum uric acid (SUA), Albumin, lipid profiles and etc. according to five components of MetS. Our result shows that SHBG could contributed to some laboratory parameters such as LDL-C (P<0.05), total cholesterol (P<0.05), triglycerides (P<0.05) and etc. in men, but not in women. On the other hand, we observed that concentration of SHBG is higher in patients with MetS (P<0.05); however, results from our experiment showed that there is no relation between lower level of SHBG and five components of MetS such as central obesity, raised fasting plasma glucose (FPG) (P>0.05), reduced HDL-C (P>0.05), raised triglycerides (P>0.05) and raised blood pressure (P>0.05) in both men and women. There is a significant association between SHBG and Log-Hip Circumference (P<0.05), Non-HDL-C (P<0.05) and Log-25(OH)D (P<0.05) was seen in this cross-section study in both men and women. Results obtained from our study suggest that SHBG is not a powerful enough factor to use as a predictor of MetS alone and there is no association between plasma level of SHBG and development of five components of MetS, however, lower SHBG level may contributed to lipid profiles.