Genetic analysis of nephrogenic diabetes insipidus patients: A study on the Iranian population.

INTRODUCTION: Nephrogenic diabetes insipidus (NDI) is a rare genetic disease that causes water imbalance. The kidneys play a crucial role in regulating body fluids by controlling water balance through urine excretion. This highlights their essential function in managing the body's water levels, but individuals with NDI may have excess urine production (polyuria), that leads to excessive thirst (polydipsia). Untreated affected individuals may exhibit poor feeding and failure to thrive. This disease is caused by mutations in the AVPR2 and the AQP2 genes which have the X-linked and autosomal recessive/dominant inheritance, respectively. Both of these genes are expressed in the kidney. METHODS: Twelve Iranian patients from 10 consanguineous families were studied in this project. DNA was extracted from the whole blood samples of the patients and their parents. All coding exons and exon-intron boundaries of the AVPR2 and AQP2 genes were sequenced in the affected individuals, and the identified variants were investigated in the parents. All variants were analyzed according to the ACMG (American College of Medical Genetics and Genomics) guidelines. RESULTS: In this study, 6 different mutations were identified in the patients, including 5 in the AQP2 gene (c.439G>A, c.538G>A, c.140C>T, c.450T>A, and the novel c.668T>C) and 1 in the AVPR2 gene (c.337C>T) in the present study. DISCUSSION: As expected, all the detected mutations in this study were missense. According to the ACMG guideline, the identified mutations were categorized as pathogenic or likely pathogenic. Unlike previous studies which showed more than 90% of mutations were in the AVPR2 gene, and only less than 10% of the mutations were in the AQP2 gene, it was found that more than 90% of our identified mutations located in the AQP2 gene, and only one mutation was observed in the AVPR2 gene, which seems it may be a result of the high rate of consanguineous marriages in the Iranian population. We observed genotype-phenotype correlation in some of our affected individuals, and some of the mutations were observed in unrelated families from same ethnicity which could be suggestive of a founder mutation.

Process optimization for green synthesis of silver nanoparticles using Rubus discolor leaves extract and its biological activities against multi-drug resistant bacteria and cancer cells.

Multi-drug resistant (MDR) bacteria are considered a serious public health threat. Also, increasing rate of resistance to anticancer drugs, as well as their toxicity, is another point of concern. Therefore, the new antibacterial and anticancer agents are always needed. The synthesizing silver nanoparticles (AgNPs) using medicinal plants, is an effective approach for developing novel antibacterial and anticancer agents. Rubus discolor, a native species of the Caucasus region, produces leaves that are typically discarded as a by-product of raspberry production. The present study has focused on optimizing the green synthesis of AgNPs using R. discolor leaves extract through response surface methodology. The optimal values for AgNPs synthesis were an AgNO3 concentration of 7.11 mM, a time of 17.83 h, a temperature of 56.51 °C, and an extract percentage of 29.22. The production of AgNPs was confirmed using UV-visible spectroscopy (λmax at 456.01 nm). TEM analysis revealed well-dispersed AgNPs (an average size of 37 nm). The XRD analysis confirmed the crystalline structure. The EDX detected a strong peak at 3 keV corresponded to Ag. The zeta potential value (- 44.2 mV) indicated the stability of nanoparticles. FT-IR spectra showed the presence of various functional groups from plant compounds, which play an important role in the capping and bio-reduction processes. The AgNPs revealed impressive antibacterial activities against MDR Escherichia coli and Pseudomonas aeruginosa (MIC ranging from 0.93 to 3.75 mg ml-1). The phytochemical analysis indicated the presence of phenolics, tannins, and flavonoids on the surface of AgNPs. They also showed significant cytotoxic effects on A431, MCF-7, and HepG2 cells (IC50 values ranging from 11 to 49.1 µg ml-l).

Isolation and structure elucidation of the compounds from Teucrium hyrcanicum L. and the investigation of cytotoxicity, antioxidant activity, and protective effect on hydrogen peroxide-induced oxidative stress.

BACKGROUND: Teucrium hyrcanicum L. (family Lamiaceae) is widely distributed in the North and Northwest of Iran. It has been used in the form of tea, tonic, and tincture for the treatment of various diseases such as cough, rheumatism, and fever. METHODS: In this study, the total phenolic and flavonoid contents, antioxidant and cytotoxic activities of methanol extract and different fractions of T. hyrcanicum were measured. Furthermore, the potential ability of T. hyrcanicum to protect against H2O2-induced oxidative stress was tested on the NIH3T3 cell line. Then, the isolation and structure elucidation of the compounds were performed on the most potent fractions. Finally, the quantification of isolated compounds in methanol extract (ME) was done by the HPLC method. Isolated phytochemicals were assessed for the cytotoxic and antioxidant activities. RESULTS: The results indicated that the methanol fraction (MF) had the highest amount of phenolic and flavonoid contents (69.36 mg GAE/g extract and 68.95 mg QE/g extract). The highest radical scavenging activities were observed from MF and ME (IC50 44.32 and 61.12 µg.ml-1, respectively). The best cytotoxicity was obtained by ethyl acetate fraction (EF) against A431 and MCF7 cell lines (IC50 values of 235.4and 326.6 µg.ml-1, respectively). The pretreatment with MF exerts the highest reduction in malondialdehyde (MDA) formation (IC50 2.51 µM, p < 0.001) compared to the H2O2 group (5.77 µM). Also, MF significantly inhibited H2O2-induced Glutathione (GSH) oxidation (p < 0.001). Furthermore, two phenolic compounds, acteoside and quercetin, were isolated and identified in MF and EF, respectively. The IC50 values of acteoside and quercetin in the DPPH assay were 7.19 and 5.56 µg.ml-1, respectively. Both quercetin and acteoside significantly reduced the MDA formation and inhibited GSH oxidation, which was comparable with BHA (as a standard antioxidant) (p < 0.05). Acteoside demonstrated significant cytotoxicity against all tested cell lines (IC50 = 32 to 145 µg.ml-1). The HPLC quantification of isolated compounds revealed that the quantity of acteoside and quercetin in ME were 93.31 and 16.87 µg.mg-1, respectively. CONCLUSION: The isolated compounds (quercetin and acteoside) had significant antioxidant activities and revealed a protective effect on H2O2-induced oxidative stress which was comparable with BHA.

The effect of educational program based on the clinical practice protocol on treatment adherence, self-efficacy and quality of life of patients undergoing coronary artery bypass graft surgery.

BACKGROUND AND AIM: Educating the patients undergoing coronary artery bypass graft (CABG) before and after surgery is one of the most important factors for success in this surgery, as it improves their treatment adherence, self-efficacy, and quality of life. The aim of this study was to determine the impact of the educational program based on clinical practice protocol upon treatment adherence, self-efficacy, and quality of life of patients undergoing CABG surgery in Tehran, Iran, during the period 2021-2022. MATERIALS AND METHODS: This experimental study was conducted on 100 patients who were undergoing CABG and were hospitalized in a public hospital (Shahid Modarres Educational Hospital) in Tehran, Iran, in 2021-2022. Patients were randomly assigned to intervention (n = 50) and control (n = 50) groups. Four questionnaires (demographic-clinical questionnaire, Modanloo's adherence to treatment questionnaire, Sullivan's self-efficacy questionnaire, and McNew's quality of life questionnaire) were completed by both intervention and control groups before and 1 month after the educational intervention. The intervention group received an education program based on the clinical practice protocol. Data were analyzed using descriptive and inferential methods in Statistical Package for the Social Sciences (SPSS) 22 software. RESULTS: The results of the study showed that the intervention and control groups were similar in terms of demographic and clinical characteristics. The average scores of treatment adherence, self-efficacy, and quality of life 1 month after the intervention were significantly higher in the intervention group compared to the control group. Also, the average scores of treatment adherence, self-efficacy, and quality of life were significantly higher 1 month after the intervention than before in the intervention group (P < 0.001). CONCLUSIONS: The results of this study showed that education program based on the clinical practice protocol can be effective and useful for increasing the level of treatment adherence, self-efficacy, and quality of life of patients undergoing CABG.

Exploring the Impacts of Caring for Hospitalized COVID-19 Patients on Nurses: A Qualitative Descriptive Study.

Background: The impacts of caring for hospitalized COVID-19 patients on nurses are wide and varied and have not been comprehensively explained in the existing literature. The aim of this study was to explore the nurses' perception of the impacts of caring for hospitalized COVID-19 patients. Materials and Methods: In this qualitative descriptive study, data were collected via semi-structured interviews with 20 nurses and head nurses of emergency/internal wards and Intensive Care Units (ICUs) of 2 hospitals in Tehran, Iran. The purposive sampling method was used, and data analysis was performed using a conventional content analysis approach. Results: After data analysis, 12 subcategories, 3 main categories, and 1 theme (professional resilience) were extracted. The three main categories included "complex care," "professional development," and "caring self-efficacy." Caring for hospitalized COVID-19 patients was complex for nurses; however, the care provided to these patients could also lead to the nurses' professional development and caring self-efficacy. Conclusions: Health organizations and nursing managers can better manage the COVID-19 pandemic and other similar future crises through strategies such as providing nurses with adequate and diverse resources and facilities, encouraging and supporting nurses in various dimensions, providing positive media advertisements for the nursing profession and nurses, and providing nurses with necessary and applicable knowledge and skills.

Exopolysaccharide from the yeast Papiliotrema terrestris PT22AV for skin wound healing.

INTRODUCTION: Exopolysaccharides (EPSs) are high-value functional biomaterials mainly produced by bacteria and fungi, with nutraceutical, therapeutic and industrial potentials. OBJECTIVES: This study sought to characterize and assess the biological properties of the EPS produced by the yeast Papiliotrema terrestris PT22AV. METHODS: After extracting the yeast's DNA and its molecular identification, the EPS from P. terrestris PT22AV strain was extracted and its physicochemical properties (structural, morphological, monosaccharide composition and molecular weight) were characterized. The EPS's in vitro biological activities and in vivo wound healing potential were also evaluated. RESULTS: The obtained EPS was water-soluble and revealed an average molecular weight (Mw) of 202 kDa. Mannose and glucose with 97% and 3% molar percentages, respectively, constituted the EPS. In vitro antibacterial activity analysis of the extracted EPS exhibited antibacterial activity (>80%) against Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis at a concentration of 2 mg/mL. The EPS showed cytocompatibility against the human fibroblast and macrophage cell lines and the animal studies showed a dose-dependent wound healing capacity of the EPS with higher wound closure at 10 mg/mL compared to negative and positive control after 14 days. CONCLUSION: The EPS from P. terrestris PT22AV could serve as a promising source of biocompatible macromolecules with potential for skin wound healing.

Phytochemical analysis, antioxidant, cytotoxic, and antimicrobial activities of golden chamomile (Matricaria aurea (Loefl.) Schultz Bip).

Matricaria aurea (Loefl.) Schultz Bip. (Asteraceae), known as golden chamomile, has been traditionally used for the treatment of various diseases. In this study, total phenolic, flavonoid, and tannin contents of total extract and different fractions of this plant were determined. The antioxidant, cytotoxic, and antimicrobial activities were also evaluated. Moreover, the phenolic profiles of selected fractions were determined by HPLC and LC-MS/MS analysis. Results demonstrated total phenolic contents of 37.8-57.2 mg GAE/g and total flavonoid contents of 3.0-111.2 mg QE/g. The ethyl acetate and methanol fractions (EF and MF) had the highest concentrations of phenolic, tannin, and flavonoid compounds. In both DPPH radical scavenging assay and phosphomolybdenum reduction assay, EF showed the best antioxidant activity, followed by MF. EF and MF indicated also the best antibacterial activities against Bacillus subtilis (MIC 1.56 and 12.5 mg ml-1) and Staphylococcus aureus (MIC 0.78 and 12.5 mg ml-1). Hexane fraction (HF) had no antibacterial effect. None of the samples had antifungal effect. MTT (3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay revealed for EF and HF the highest antiproliferative activities (IC50 values ranged from 111.8 to 294.6 µg ml-1). The presence of chlorogenic acid, ferulic acid, and luteolin-7-O-glucoside in MF, and p-coumaric acid in EF was confirmed and quantified.

Apoptosis Effects of Oxalis corniculata L. Extract on Human MCF-7 Breast Cancer Cell Line:.

Background: Recently, the non-toxic properties of natural plant products have gained more focus as anticancer agents. Therefore, this study aimed to assess the apoptosis effects of the ethanolic extract of Oxalis corniculata on the MCF-7 breast cancer cell line.Materials and Methods: In this experimental study, aerial parts of O. corniculata were collected in Lahijan city (Iran), and after confirmation, they were dried and extracted with ethanol for 24 h. Then, the total phenolic and flavonoid contents of the extract were measured. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay was used to measure the antioxidant properties of the extract. Selected cell lines (MCF-7 and human dermal fibroblast) were cultured in 6-wells dishes (1×106 cells/well). After 72 h of treating the extract, cytotoxicity was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The expression of apoptotic genes (such as p53, bcl-2, bax, and CD95) was studied by real-time polymerase chain reaction (PCR). Results: The extract's total phenolic content was 31.30±02 µg of gallic acid equivalents/mg of dry extract, and the total flavonoid content was 49.61±04 µg of quercetin as equivalents/mg of extract. The antioxidant activity ofO. corniculata was measured at the dose of 619.2 µg/µl, indicating that it decreases cancer cell viability and enhances apoptosis. Within the half maximal inhibitory concentrations, real-time PCR revealed substantial increases in p53 (P<0.001), CD95 (P<0.05), and bcl-2 expression (P<0.05) in MCF-7 cells treated with O. corniculata. Conclusion: This study suggests that O. corniculata may cause apoptosis by oxidative stress in cancer cells.[GMJ.2022;11:e2484].

Protection Behaviors and Related Factors Against COVID-19 in the Healthcare Workers of the Hospitals in Iran: A Cross-Sectional Study.

Background: Protective behaviors play a key role in reducing the incidence of COVID-19 in HealthCare Workers (HCWs), and these behaviors are related to other factors. These related factors have not been comprehensively evaluated and determined in the literature. This study aimed to determine protection behaviors against COVID-19 and their related factors using the Protection Motivation Theory (PMT) among HCWs of hospitals in Tehran, Iran, in 2021. Materials and Methods: For this cross-sectional study, 270 HCWs of different wards in 3 hospitals in Tehran, Iran, were selected through multistage sampling (April to July 2021). The participants completed a self-reporting questionnaire which consisted of a demographic characteristics form and questions about protective behaviors against COVID-19 and other constructs of the PMT (60 items). Data analysis was performed using descriptive and inferential methods. Results: The mean score of the protective behaviors of the HCWs was 4.20 (SD = 0.56) and was significantly higher in the nurses, women, married individuals, and those with a BSc degree compared with others (p < 0.05). Furthermore, the results of multiple regression analysis showed that protection behavior among HCWs could be strongly predicted by the type of profession, protection motivation/intention, and self-efficacy constructs (F14, 255 = 16.34, p < 0.001). Conclusions: The protection behaviors of HCWs against COVID-19 were relatively desirable and these behaviors were related to and predicted by various factors. These results could apply to developing plans for protective behaviors against COVID-19 and possibly other infectious diseases among HCWs. Further research in this regard is recommended.

Professional Responsibility and Its Related Factors among Bachelor Degree Nursing Students in Iran: A Cross-Sectional Study.

BACKGROUND: Professional responsibility is important for bachelor degree nursing students, but it has not been measured specifically among these students and findings of the studies on its related factors are inconsistent. This study aimed to determine the level of professional responsibility and its related factors among bachelor degree nursing students in selected public nursing schools in Iran. MATERIALS AND METHODS: For this cross-sectional study, 388 bachelor degree nursing students from 8 selected public nursing schools in Iran were selected through convenience sampling (2018-2019). The participants completed the demographic questionnaire and Responsibility among Bachelor Degree Nursing Students Scale (RABDNSS). This valid and reliable scale consists of 45 items that determine professional responsibility and its 5 subscales. Data were analyzed using descriptive and inferential methods in SPSS software. RESULTS: The mean (SD) total score of professional responsibility was 175.26 (23.58), indicating a high level of responsibility. The highest and lowest mean (SD) scores were obtained in the subscales of situational self-mandatory 4.20 (0.52) and positive professional attitude 3.71 (0.82), respectively. Students' educational grade average and level of interest in nursing were significantly correlated with professional responsibility and its subscales (p < 0.05). CONCLUSIONS: The relationship of students' interest in nursing and students' educational grade average with professional responsibility can be useful for planning admission policies and evaluating and promoting professional responsibility related behaviors among nursing students. However, further research in these areas is recommended.

Design, Synthesis and Biological Evaluation of Novel Piperazinone Derivatives as Cytotoxic Agents.

Purpose: In this study, a series of piperazin-2-one derivatives were prepared through bioisosteric substitution of the imidazole ring of L-778,123 (imidazole-containing FTase inhibitor) and rearrangement of groups based on the tipifarnib structure. Final compounds were evaluated for their cytotoxic activities on cancer and normal cell lines by MTT assay. Methods: Methyl α-bromophenylacetic acid and 1-(3-chlorophenyl) piperazin-2-one were synthesized using previously described methods. Methyl 2-(4-chlorophenyl)-2-(4-(3- chlorophenyl)-3-oxopiperazin-1-yl) acetate was prepared by reaction between these two compounds in presence of potassium carbonate. Finally, methoxy group of ester was substituted by various amines such as guanidine, thiourea, urea and hydrazide. The synthesized compounds were tested for their cytotoxicity against colon cancer (HT-29) and lung cancer (A549) cell lines as well as MRC-5 (normal fetal lung fibroblasts) cells as a healthy cell line using MTT colorimetric assay method. Results: Replacement of imidazole moiety with guanidine, thiourea, and hydrazide could increase cytotoxicity toward all three cell lines. Some substituents, such as amine, urea, and hydroxylamine exhibited significant cytotoxicity (<500 µM) but lower than L-778,123 as standard compound. Hydroxyl and methoxy substituents did not show significant cytotoxicity. Imidazole substituent group revealed cytotoxicity similar to L-778,123 All compounds showed lower cytotoxic activity against normal cell lines compared with cancer cell lines. Conclusion: It seems the electron density of substituted groups and rearrangement of groups may significantly increase cytotoxic activity.

The effect of aromatherapy with rose and lavender on anxiety, surgical site pain, and extubation time after open-heart surgery: A double-center randomized controlled trial.

To determine the effect of aromatherapy with rose and lavender on the patient outcomes after open-heart surgery (OHS). In the clinical trial, patients were randomized to four groups. One group received routine care, the placebo group received a cotton swab soaked in water and the other two groups received either a cotton swab containing three drops of rose or lavender essence (0.2 ml). A total of 160 patients were randomized into four groups. Intergroup anxiety was not significantly different; however, the reciprocal time-group effect was significant among the four groups. The extubation time was significant among the four groups which related to rose essence group compared with the control group (p < .001) and placebo group (p = .029). The surgical site pain was significant in the rose essence and lavender groups compared to the control group. Aromatherapy can reduce extubation time, surgical site pain severity, and anxiety in patients undergoing OHS.

Professional responsibility-acquiring process among bachelor degree nursing students: A grounded theory study.

INTRODUCTION: Professional responsibility-acquiring process among bachelor degree nursing students is important for their current and future performance and educational and health-care system, but this process has not been explored in the literature. The aim of the current study is to explore the process of acquiring professional responsibility among bachelor degree nursing students. METHODOLOGY: The study design was based on grounded theory (Corbin and Strauss 2015). Purposive and theoretical sampling led to the inclusion of 18 individual interviews and a focus group interview with bachelor degree nursing students, their instructors, and key informants in a nursing school and university, an educational hospital, and a health comprehensive service center in Tehran in 2019-2020. RESULTS: After data analysis, 6 categories, 17 primary categories, 64 subcategories, and 1747 initial codes were extracted. Trying to optimal use of the educational period was the main category of this study and its primary categories were responsible learning and performance management strategies, there were facilitators and inhibitors categories for applying these strategies. Personal, educational, and professional context factors were primary categories that may lead to the main concern (uncertain productivity of the educational period) with regard to acquiring professional responsibility. Protection of the students and others versus irresponsibility was consequence category of this process. CONCLUSION: Knowing the process of acquiring professional responsibility among bachelor degree nursing students can be used to facilitate the formation, promotion, and evaluation of professional responsible behaviors. Further researches in these areas are recommended.

Medium containing different concentrations of catalase as a strategy for optimising sperm parameters and chromatin in normospermic persons.

The aim of this study was to comprise the effect of catalase on sperm parameters and chromatin in normospermic persons. Semen samples were obtained from fertile men. A certain amount of different concentrations of catalase (0.1, 1, 10, 50, 100, 150 and 200 IU.ml) was added to each vial containing semen. Control group had similar condition to treated groups without treatment. Treatment was done for one hour in incubator and 4 and 24 hr in room temperature. Sperm parameters (motility, viability and morphology) and chromatin were evaluated after incubation. The results show that percentage of motility was insignificantly increased at concentration of 100 IU.ml catalase. This increase was higher than other examined concentration in all incubation time. The increase in sperm motility had significant difference in concentrations of 100 IU.ml with other concentrations. Other parameters showed no significant difference in all concentrations. Regarding the health of sperm chromatin, low concentrations of catalase had significant effect on this variable. This effect was more in low concentrations than high concentrations. This study showed the use of lower concentrations of antioxidant can improve the sperm parameters and chromatin quality. The low concentrations of catalase led to protection of chromatin and optimisation of sperm parameters.

Responsibility among bachelor degree nursing students: A concept analysis.

BACKGROUND: Responsibility is an important component of the professional values and core competencies for bachelor degree nursing students and has relationships with nursing education and professionalization. It is important for providing safe and high-quality care to the clients for the present and future performance of student. But there is no clear and operational definition of this concept for bachelor degree nursing students; however, there are extensive contents and debates about the definitions, attributes, domains and boundaries of responsibility in nursing and non-nursing literature. OBJECTIVE: To examine the concept of responsibility among bachelor degree nursing students using the evolutionary approach to concept analysis. METHODS: A total of 75 articles published between 1990 and 2016 and related to the concept of responsibility were selected from seven databases and considered for concept analysis based on Rogers' evolutionary approach. ETHICAL CONSIDERATIONS: Throughout all stages of data collection, analysis and reporting, accuracy and bailment were respected. FINDINGS: Responsibility is a procedural, spectral, dynamic and complex concept. The attributes of the concept are smart thinking, appropriate managerial behaviours, appropriate communicational behaviours, situational self-mandatory and task-orientation behaviours. Personal, educational and professional factors lead to the emergence of the responsible behaviours among bachelor degree nursing students. The emergence of such behaviours facilitates the learning and education process, ensures nursing profession life and promotes clients and community health level. Responsibility has some effects on nursing students. DISCUSSION: This concept had been changed over time since 1990-2016. There are similarities and differences in the elements of this concept in disciplines of nursing and other educational disciplines. CONCLUSION: The analysis of this concept can help to develop educational or managerial theories, design instruments for better identification and evaluation of responsible behaviours among bachelor degree nursing students, develop strategies for enhancing the responsibility and improve the safety and quality of nursing care in the community and healthcare system.

Investigation of phenolic compounds and antioxidant activity of leaves extracts from seventeen cultivars of Iranian olive (Olea europaea L.).

The leaves of seventeen cultivars of olive growing in the north of Iran were investigated for total phenol content and antioxidant activity. The identification and quantification of main phenolic compounds were performed by reverse phase high performance liquid chromatography with diode array detector. The cultivars Kalamon, Gordal, and Coratina contained the highest concentration of phenolic compounds (190.65 ± 0.03, 184.72 ± 0.001, and 155.91 ± 0.06 mg GAE/g extract, respectively). The maximum radical scavenging activities were found in Gordal, Coratina, and Kalamon extracts (IC50 20.66, 22.95, and 26.74 µg ml-1, respectively). The extracts of Mishen, Fishomi, and Arbequina (1971.37 ± 0.007, 1794.57 ± 0.001, and 1760.57 ± 0.005 µmol Fe II/g dried extract, respectively) showed highest antioxidant activity in FRAP assay. The identification analysis demonstrated the present of vanillin, rutin, luteolin 7-O-glucoside, oleuropein, and quercetin. The highest oleuropein concentrations were detected in cultivars Mishen, Beleidi, Kalamon, and Roghani while it was not detected in cultivars Conservolea, Amigdalolia, Leccino, and Fishomi.

2D-QSAR study of some 2,5-diaminobenzophenone farnesyltransferase inhibitors by different chemometric methods.

Quantitative structure activity relationship (QSAR) models can be used to predict the activity of new drug candidates in early stages of drug discovery. In the present study, the information of the ninety two 2,5-diaminobenzophenone-containing farnesyltranaferase inhibitors (FTIs) were taken from the literature. Subsequently, the structures of the molecules were optimized using Hyperchem software and molecular descriptors were obtained using Dragon software. The most suitable descriptors were selected using genetic algorithms-partial least squares and stepwise regression, where exhibited that the volume, shape and polarity of the FTIs are important for their activities. The two-dimensional QSAR models (2D-QSAR) were obtained using both linear methods (multiple linear regression) and non-linear methods (artificial neural networks and support vector machines). The proposed QSAR models were validated using internal validation method. The results showed that the proposed 2D-QSAR models were valid and they can be used for prediction of the activities of the 2,5-diaminobenzophenone-containing FTIs. In conclusion, the 2D-QSAR models (both linear and non-linear) showed good prediction capability and the non-linear models were exhibited more accuracy than the linear models.

SULF 1 gene polymorphism, rs6990375 is in significant association with fetus failure in IVF technique.

BACKGROUND: Sulfatase 1 (SULF1) function is to remove the 6-O-sulphate group from heparan sulfate. This action changes the binding sites of extracellular growth factors. SULF1 expression has been reported to be changed in angiogenesis. We hypothesized that single nucleotide polymorphisms (SNPs) of SULF1 would impact clinicopathologic characteristics. OBJECTIVE: Study of SULF1 gene polymorphism with fetus failure in in vitro fertilization (IVF) technique. MATERIALS AND METHODS: We studied one common (minor allele frequency >0.05) regulatory SNP, rs6990375, with polymerase chain reaction and restriction fragment length polymorphism method, in 53 infertile women with fetus failure in IVF technique and 53 women with at least one healthy child as controls. RESULTS: We found that rs6990375 is significantly associated with an early failure in IVF and frequency of G allele is high in women with fetus failure in IVF technique (p<0.001). CONCLUSION: These findings suggest that SULF1genetic variations may play a role in IVF technique fetus failure. Further studies with large sample sizes on SULF1 SNPs may be useful in support of this claim.

Functional liposomes in the cancer-targeted drug delivery.

Cancer is considered as one of the most severe health problems and is currently the third most common cause of death in the world after heart and infectious diseases. Novel therapies are constantly being discovered, developed and trialed. Many of the current anticancer agents exhibit non-ideal pharmaceutical and pharmacological properties and are distributed non-specifically throughout the body. This results in death of the both normal healthy and malignant cells and substantially leads to accruing a variety of serious toxic side effects. Therefore, the efficient systemic therapy of cancer is almost impossible due to harmful side effects of anticancer agents to the healthy organs and tissues. Furthermore, several problems such as low bioavailability of the drugs, low drug concentrations at the site of action, lack of drug specificity and drug-resistance also cause many restrictions on clinical applications of these drugs in the tumor therapy. Different types of the liposomal formulations have been used in medicine due to their distinctive advantages associated with their structural flexibility in the encapsulation of various agents with different physicochemical properties. They can also mediate delivery of the cargo to the appropriate cell type and subcellular compartment, reducing the effective dosage and possible side effects which are related to high systemic concentrations. Therefore, these novel systems were found very promising and encouraging dosage forms for the treatment of different types of cancer by increasing efficiency and reducing the systemic toxicity due to the specific drug delivery and targeting.

Pioglitazone prevents morphine antinociceptive tolerance via ameliorating neuroinflammation in rat cerebral cortex.

BACKGROUND: Opioid induced neuroinflammation is shown to be implicated in opioid analgesic tolerance development. In the present study the effect of pioglitazone on morphine-induced tolerance and neuroinflammation in the cerebral cortex of the rat was investigated. MATERIALS AND METHODS: Various groups of rats received morphine (10mg/kg; ip) and vehicle (po), or morphine (10mg/kg) and pioglitazone (20 or 40 mg/kg; po) once a day for 17 days. In order to determine the possible involvement of PPAR-γ in the pioglitazone effect, one group of rats received PPAR-γ antagonist, GW-9662 (2mg/kg; sc), and pioglitazone (40 mg/kg) and morphine once daily for 17 days. Nociception was assessed using a tail flick apparatus and the percentage of the maximal possible effect was calculated as well. On 18th day, 2h after the last morphine injection, the cerebral cortex of the animals were harvested and the tissue levels of tumour necrosis factor alpha, interleukin-1beta, interleukin-6, interleukin-10 and nuclear factor-kappa B activity were determined. RESULTS: Co-administration of pioglitazone (40 mg/kg) with morphine not only attenuated morphine-induced tolerance, but also prevented the up-regulation of pro-inflammatory cytokines (tumour necrosis factor alpha, interleukin-1beta, interleukin-6) and nuclear factor-kappa B activity in the rat cerebral cortex. Moreover, GW-9662 (2mg/kg) administration 30 min before pioglitazone, antagonized the above mentioned pioglitazone-induced effects. CONCLUSION: It is concluded that oral administration of pioglitazone attenuates morphine-induced tolerance. This effect of pioglitazone may be, at least in part, due to its anti-inflammatory property which suppressed the cortical pro-inflammatory cytokine and inhibited of nuclear factor-kappa B activity.