Formulation and In-Vitro Evaluation of Rosuvastatin Nanoemulsions

Introduction: Rosuvastatin (ROS) calcium is the latest synthetic drug in the statin group that has an anti-hyperlipidemic activity. It is available as tablets, and its poor aqueous solubility, slow dissolution rate and low-absorption extent result in less than 20% bioavailability and about 80% being excreted unchanged in the feces without absorption. The present study aimed at developing an optimal oral nanoemulsion formulation containing rosuvastatin using different proportions of oil and surfactant system for enhancing its water solubility and bioavailability. Methods and results: The solubility of ROS in different oils, surfactants and co-surfactants was tested. Based on the solubility study, liquid formulations were prepared using Arachis oil as oil phase and Tween 80 as surfactant and polyethylene 400 as co-surfactant. Pseudo-ternary phase diagrams were developed and various nanoemulsion formulations were prepared and evaluated for globule size, zeta potential, and emulsion properties. The formulations were subjected to different thermodynamic stability studies such as centrifugation, heating-cooling cycle and freeze-thaw cycle, to avoid the selection of metastable formulations. Transmittance study and in-vitro dissolution studies were carried out. An optimal nanoemulsion system was successfully developed with the droplet size of 260 nm and a composition of (Arachis oil; 20%), Tween 80 (40%) and PEG 400 (40%). The cumulative percentage drug release from optimal nanoemulsion formulation was found to be 93.29±1.11% for 50 minutes, which was significantly higher than the drug suspension (43.42±1.30%). Thus, in vitro results reveal that the prepared nanoemulsion formulations showed improved solubility of ROS. Conclusions: Nanoemulsion formulations of ROS represent a promising novel formula with a higher dissolution rate when compared to the drug in suspension. &nbsp

Effect of sodium butyrate on HDAC8 mRNA expression in colorectal cancer cell lines and molecular docking study of LHX1 - sodium butyrate interaction

Colorectal cancer (CRC) is the third common cancer and the fourth leading cause of cancer related death worldwide. Histone Deacetylase 8 (HDAC8) has a unique feature and is a good target for drug design. The LHX1 factor is an important transcription factor for this gene. The aim of this study was to investigate the effect of sodium butyrate (NaB) as a histone deacetylase inhibitors on the expression of the HDAC8 gene in the colorectal cancer cell line, and the molecular docking of LHX1 transcription factor with NaB. HCT-116 and HT-29 cell lines were treated with different concentrations of NaB (6.25mM to 150 mM) at 24, 48 and 72 hours. RNA was extracted from the treated and untreated cells and cDNA was synthesized. Quantitative Real-Time-PCR was done to investigate the mRNA expression of HDAC8. Molecular docking was performed to investigate NaB and LHX1 interaction. On the base of Real-time-PCR results, the concentration of 150 mM NaB after 24 hours in HT-29 and HCT-116 cell lines caused a significant reduction in mRNA expression of HDAC8 (P<0.05). In 48 hours of treatment, there was a significant decrease in the mRNA expression of HDAC8 at all concentrations (P<0.05). The docking results showed that LHX1 and NaB interacted the best way with the lowest energy levels. Our results showed that NaB bond to LHX1 strongly. Our results demonstrated that NaB bind to the LHX1 transcription factor and inhibited the function of this factor and subsequently the transcription from the HDAC8 gene was decreased and results in cell death. Future studies are needed to assess the molecular mechanisms of NaB on gene expression

Association of rs16917496 polymorphism at the miR-502 binding site in the SET8 3'UTR with the risk of Prostate Cancer and benign prostatic hyperplasia

Background: MicroRNAs (miRNAs) can bind to the 3'-untranslated regions (UTRs) of messenger RNAs, where they interfere with translation and thereby regulate cell differentiation, apoptosis, and tumorigenesis. Genetic polymorphisms in the 3'-UTRs targeted by miRNAs alter the strength of miRNA binding in a manner that affects the behavior of individual miRNAs. The histone methyltransferase SET8 has been reported to be a regulator of Tumor Protein 53 (TP53) methylation, a tumor suppressor gene, and regulate genomic stability. Furthermore, an association between the TP53 and Prostate Cancer has been reported in several studies. The present study aimed to evaluate whether (rs16917496) polymorphism at the miR-502 binding site in the 3' untranslated region of the histone methyltransferase SET8 is associated with the expression of this gene in Benign Prostatic Hyperplasia (BPH) and prostate cancer (PCa) patients.Materials and Methods: We examined whether an rs16917496 polymorphism is associated with the risk of PCa and BPH in the Iranian population. This case-control study included 40 patients with pathologically confirmed PCa, 59 patients with BPH, and 45 controls. The rs16917496 polymorphism was determined using a restriction fragment length polymorphism (RFLP).Results: We found significant association of rs16917496 in benign prostatic hyperplasia (BPH). The most frequent genotype in the control, prostate cancer, and BPH groups were TT, TC, and CC, respectively.Conclusion: This study demonstrates that the heterozygote genotype of the SET8 polymorphism in the mir-502 gene could be considered a risk factor for the emergence of prostate cancer

The Importance of the Place of Comparative Approach in the History of Persian Folk Literature and Criticism of Arabic Poetry and Prose Texts, the Heading of Folk Literature, Master's Degree in Persian Language and Literature

1.IntroductionAfter the term "Folklore" was coined by Ambroise Morton in 1846 and the beginning of research on folk literature and culture, Studies related to this field had many developments and scientific advances. Research in the field of Persian folk culture and literature also began with the research of orientalists (see Afshari, 1388: 289).After that, even despite the increasing process of recording the components of folk culture and literature and even the establishment of the orientation of folk literature in 2013 and the specialization of studies in this field in Iran, the research conducted in this field still has obvious flaws. Stopping at the stage of registering the components of folk literature, the ambiguity in the structure and characteristics of these components, and most importantly, the weakness in the theoretical foundations are among the most important things that can be pointed out (see. Aliani et al, 2019: 10).One of the main reasons for this issue is the neglect of the Arabic sources of the early Islamic centuries as the preservers of Iranian folklore culture and literature in the era of the loss of Persian sources and neglect in the history of folklore Persian literature.. "It is an important issue that the Arabic language played an important role as the preserver of Iranian folklore literature before Islam." (Cejpek, 2014: 27 & 26). Despite this, in addition to the researches that have been done in the field of folklore culture and literature, the importance of these resources and the effective role of the comparative approach have not been paid attention to in the design of the  lessons of the folkliterature orientation. Especially since in the list of courses of this heading, there is a course called "Arabic Prose and Poetry" in which these sources are expected to be paid attention to, but these sources were not paid attention to in its design.Based on this, in this article, while explaining the reasons for the importance of these sources, the most important available Arabic sources are introduced in terms of the reflection of Iranian folk literature and its developments in the first centuries of Islam, And in order to eliminate the existend shortcomings, a heading has been designed for the course "Arabic Poetry and Prose Texts". 2.MethodologyConsidering the need to refer to Arabic sources for the historical connection of the elements and components of Iranian culture and literature before Islam with the Islamic era, this research has been done by descriptive-analytical method and by analyzing the literature history data available in the library sources. 3.DiscussionThe task of transferring Iranian culture and literature to Arabic culture and language in the first centuries of Islam has been undertaken by the translation movement. "Many sources of the past folklore of Iran have been translated into Arabic by Iranian scholars such as Ibn Moqfa, Tabari, Masoudi, Thaalebi, Hamzeh Isfahani and others and are available to us today." (Beihaghi, 1365: 41). Despite this, the heading designed for Arabic poetry and prose lesson of the heading of Persian folk literature in order to get familiar with official Arabic literature, including Arabic mystical texts, poems by Arab poets, Arabic works by Persian poets and writers, and contemporary Arabic research texts in the field of language and literature, the Qur'an, Nahj al-Balagha, and commentary texts,  Arabic proverbs, phrases and verses common in Persian texts. The general approach and a cursory look in the selection of texts and the focus of this heading on official literature texts and neglecting the importance of the comparative approach do not meet the scientific needs of students in this field. Therefore, the issue of interest in this article is that despite the many reasons for the high importance of Arabic texts in the history of Iranian folk literature, how the sources of Arabic poetry and prose texts in the heading of folk literature to explain the nature of Iranian folk culture and literature and its developments In the first centuries of Islam and attention to the importance of the comparative approach has not been organized?Reasons for the importance of the comparative approach in the history of Persian folk literatureSome of the most important intratextual and extratextual reasons for the importance of Arabic sources in the field of Iranian folk culture and literature are as follows:1.The existence of different forms of Iranian folk stories and proverbs and and anecdotes in Arabic sources: in many cases, these sources have become the oldest or only sources of Iranian folklore stories. Such as the reflection of a story about Ardeshir Babkan, in the book "nehayat-al-arab" under the name of Irajosteh and Khosrow in the persian translation of Varavini's Marzbannameh.The importance of the works of Arabic-speaking Iranian writers and poets, especially the Shaoubians, in terms of recording the components of Iranian folk literature: The Shaoubieh movement is one of the most important factors in the transfer of Iranian folk culture and literature to Arabic culture and sources. The works of this group, such as Ibn Muqafa, Mahmoud vorraq, Saleh ibn Abd al-Quddus and Bashar ibn Burd, contain a large number of poetice or prose form of components of Iranian folk literature such as Iranian proverbs and admonition in ArabicIn Arabic: “The tooth is still worn out, and the one who has it is still in pain and is leaving it.  ” (Ibn Muqaffa, 2002: 140).In Persian: " The eaten by worm (destroyed) tooth of the  should be removed " (Amini, 2009: 287).The importance of Arab collections(collections of poetries and writers works and folklore content too) in Iranian folk culture and literature: whith spread of a new style in Arabic writings is via Jahiz Basri  (under name of collection writing)  and the creation of numerous works imitating it, the reflecting ideas, admonitions and anecdotes related to folklore culture and literature in written works increased. The reflection of some common beliefs in Iranian culture in Abu hayyan Tawhidi's Al-Emta va Al-Moanesat about trees, animals and mineral stones is one of these (cf. Tawhidi, 2005: 235).The need to pay attention to the literary components in Arabic sources that have a folk origin: one of the main necessary steps in explaining the importance of Arabic written sources in the field of Iranian folk literature is to pay attention to the literary components that have a folk origin. "There has been a continuous mutual influence between written and oral literature" (wellek, 2013: 41 & 42). Fables, parables, jokes, Arabic folk poems of Iranian origin, quatrains, and beggars' stories originating from Iranian culture are among the most important of this group.5. The importance of Arabic sources in terms of recording the legendary history of Iranians and its importance in the discussion of mythological studies: the translation of Iranian history sources into Arabic, especially the "Khuday nameh", and the comparison of different characterizations of Iranian mythological champions such as Rostam in these sources with the Shahnameh and Iranian folk culture, It doubles the importance of Arabic sources in studying the history of developments in Iranian mythology.The influence of Arabic-Islamic culture on the components of Iranian folk literature: When discussing the importance of Arabic sources in the discussion of Iranian folklore literature, it is necessary to consider the effects of Arabic-Islamic culture on Iranian public culture and literature. including the influence of Arabic proverbs and admonitions and the importance of influence of Semitic and Islamic history in the discussion of comparative mythology and the spread of Arabic love stories in Iranian culture.Authors and important works: the works of Ibn Muqafa as the first collections containing Iranian proverbs and rulings after Islam, the works of Jahiz, the important work of Abu al-Faraj Isfahani called Al-Aghani, the works of Thaalibi Neishabouri, the book of Abu hayyan Tawhidi’s Al-EMtaa and Al-Mu’anasat, the works of Qazi Mohsen Tanukhi and the work of Ragheb Isfahani With the name of Mohazerat al-odaba va Mohaverat al-shoara va al-bolagha, which contain verse and prose form of proverbs and admonitions, anecdotes, stories, superstitions, Arabic stories that are influential in Iranian culture, jokes and popular opinions. these cases are the most important things is the importance of Arabic sources in reflecting folk culture and literature.Designing the heading of the Iranian folk culture and literature course in Arabic poetry and prose texts: based on the discussed topics, it is suggested to change the title of the Arabic poetry and prose texts course in the Persian folk literature heading to "Iranian folk culture and literature in Arabic prose and poetry texts" and educational topics should be organize under these main headings:"The importance and role of Nahj al-Balagha and the Holy Quran in Iranian folk culture and literature""Iranian admonitions, Arabic admonitions and understanding the importance of moral and religious admonitions and advice in Iranian culture (before and after Islam)"" Iranian proverbs in sources of Arabic proverbs, Arabic proverbs, stories of proverbs, examples of Arabic poems by Iranian poets (poetice form of proverbs and admonitions)""The importance of historical sources in the analysis and investigation of Iranian, Semitic and Islamic mythology and how to synchronize them"" Analysis and investigation of Iranian folk culture and literature in the Arabic collections""Study of Arabic love stories introduced into Persian culture and literature""The influence of folk culture and literature in the creation of the literary type of Maghameh""Jokes and comical in Arabic sources""Familiarization with the research texts of Arabic writers in the field of the connection between Iranian folk culture and literature with Arabic and Islamic culture and literature". 4.ConclusionThe current heading of the course on Arabic poetic and prose texts of the folk literature major does not fit with the goals and nature of the major. In the design of the proposed heading in this article, three effect-oriented, component-oriented and research-oriented approaches have been considered. In teaching these cases, you can pay attention to these three approaches. This means that in effect-oriented cases, the focus should be on the study of literary components that have an impact on people's culture, in component-oriented cases, emphasis should be placed on comparing and studying the course of changes in literary components, and in research-oriented cases, emphasis should be placed on the reflection of various components of Iranian folk culture in the Arabic collections. By presenting such cases, it is possible to solve part of the historical problem regarding the nature of Iranian folk culture and manners after Islam, and to direct students' minds to the importance of theoretical foundations in research in this field

Characterization of perfect Roman domination edge critical‎ ‎trees

‎A perfect Roman dominating function on a graph $G =(V‎, ‎E)$ is a function $f‎: ‎V \longrightarrow \{0‎, ‎1‎, ‎2\}$‎ ‎satisfying the condition that every vertex $u$ with $f(u) = 0$ is adjacent to exactly one vertex‎ ‎$v$ for which $f(v) = 2$‎. ‎The weight of a perfect Roman dominating function $f$ is the sum of‎ ‎the weights of the vertices‎. ‎The perfect Roman domination number of $G$‎, ‎denoted by $\gamma_{R}^{p}(G)$‎, ‎is‎ ‎the minimum weight of a perfect Roman dominating function in $G$‎. ‎In this paper‎, ‎we study the‎ ‎graphs for which adding any new edge decreases the perfect Roman‎ ‎domination number‎. ‎We call these graphs $\gamma_R^p$-edge critical‎. ‎The purpose of this paper is to characterize the class of‎ ‎$\gamma_R^p$-edge critical trees‎

Sumatriptan effects on morphine-induced antinociceptive tolerance and physical dependence: The role of nitric oxide

Sumatriptan, a 5HT (5-hydroxytryptamine)1B/1D receptor agonist, showed neuroprotection in different studies. The aim of the present study was to investigate the effect of sumatriptan on morphine-induced antinociceptive tolerance and physical dependence. We also investigated the possible role of nitric oxide (NO) on sumatriptan effects. Tolerance was induced by morphine injection (50, 50, 75 mg/kg) three times daily for five days. Antinociceptive latency after acute and chronic treatment with sumatriptan (0.001, 0.01, 0.1 and 1 mg/kg) was measured by hot plate test in morphine-dependent animals. To investigate the possible involvement of NO, different isoforms of nitric oxide synthase (NOS) inhibitors including L-NAME, aminoguanidine and 7-nitroindazole were co-administered with sumatriptan. Nitrite level in mice hippocampus was quantified by Griess method. To examine the role of sumatriptan on physical dependence, three parameters of withdrawal signs were recorded after injection of naloxone (4 mg/kg). Acute treatment with sumatriptan (0.01, 0.1 and 1 mg/kg) attenuated the antinociceptive tolerance (P < 0.001). Chronic injection of sumatriptan (0.001, 0.01 and 0.1 mg/kg), as well, decreased the antinociceptive tolerance (P < 0.001). Moreover, co-administration of NOS inhibitors prevented the effects of sumatriptan. Sumatriptan significantly increased the level of nitrite only after chronic administration. Sumatriptan administration showed no alteration in naloxone-precipitated withdrawal signs. Acute and chronic administration of sumatriptan attenuated morphine antinociceptive tolerance; at least in chronic phase via nitrergic pathway. Our data did not support beneficial effects of sumatriptan on morphineinduced physical dependence in mice

Modelling and solving the bi-objective production–transportation problem with time windows and social sustainability

We model and solve the production routing problem (PRP) with time windows, product deterioration and split delivery. A bi-objective PRP model for a single perishable product, which is subject to deterioration, is presented. The two objectives represent the economic and social aspects of sustainability, whereas the environmental impact is enforced by incorporating ad-hoc constraints. The economic dimension of sustainability consists of minimizing the costs related to the production, setup, holding, transportation and lateness penalty. The social responsibilities are modelled through maximizing the total freshness of the delivered products at all nodes over the planning horizon. The outcomes of our formulation are represented by the lot sizes, and the amounts of product to be delivered, as well as the routing at each planning period. To solve the resulting problem, we develop an interval robust possibilistic approach, and we carry out an experimental study and a sensitivity analysis. Finally, we further validate our optimization model and solution method using a real-life case of a food factory producing a product that is subject to perishability and deterioration

Comparing Perinatal Outcome in Twin and Singleton Pregnancies Regarding Doppler Evaluation of Uterine Artery Indices in the Second Trimester

Background: Prediction of adverse perinatal and postnatal outcomes could be possible by using ultrasound Doppler evaluation, however there are some controversies regarding this issue in the literature. The goal of present study was to evaluate predictive value of Doppler indices in single and twin pregnancies during second trimester. Materials and Methods: This prospective study was conducted in Yas Hospital, Tehran, between February 2015 and January 2016. The number of 71 singleton pregnancies and 59 twin pregnancies enrolled in this study. A single expert perinatalogist / sonographer did all Doppler ultrasound exams and followed up cases until the end of pregnancy. To compare Doppler indices and pre-postnatal outcomes between singleton and twin groups, the Student’s t-test, Pearson χ2 test and Fisher’s exact test were used for continue and categorical variables, respectively. Results: Rates of preterm delivery and SGA were significantly higher in twin pregnancies compared with singletons (

Experiencing neonatal maternal separation increased the seizure threshold in adult male mice: Involvement of the opioid system

Experiencing early-life stress has been considered as a potent risk factor for the development of many of brain disorders, including seizures. Intervening mechanisms through which neonatal maternal separation (MS) alters the seizure susceptibility in adulthood have not been well studied. In the current study, by applying 180 min of MS stress (PND 2–14), we determined the seizure susceptibility and considered the role of the opioid system. Maternal separation increased the seizure threshold, and administration of anticonvulsant/proconvulsant doses of morphine (1 and 30 mg/kg, respectively) reversed the impact of MS. Using tail flick and hot plate tests, we exposed animals to 30 min Restraint stress (RS) and found that MS decreased the pain threshold, suggesting the hyporesponsiveness of the opioid system. These results supported the abnormal seizure activity observed in the MS mice and suggested that abnormalities in the opioid system following MS alter seizure susceptibility in later life