Abbas Ranjbar, Mohsen Soltanshahi, Saeid Taghiloo, Hossein Asgarian-Omran
Background: Metabolism reprogramming is a survival mechanism in acute myeloid leukemia (AML) cells in the tumor microenvironment. Therefore, we investigated the effect of signaling pathway inhibitors on the expression of genes rewired in the metabolic pathway of AML cells. Methods: HL-60 cells were treated with Idelalisib, MK-2206, and Everolimus, which respectively are selective inhibitors of phosphatidylinositol-3-kinase (PI3K), AKT, and the mammalian target of rapamycin (mTOR), either individually or in combination. The relative expressions of Glucose Transporter 1, Hexokinase 2, Pyruvate Kinase, Pyruvate Dehydrogenase E1, Citrate synthase, Isocitrate Dehydrogenase 2, and Hypoxia Inducible Factor 1 Subunit Alpha were determined by real-time PCR. Results: The combined treatment of HL-60 cells with Idelalisib, MK-2206, and Everolimus decreased the expression of Glucose Transporter 1, Hexokinase 2, Pyruvate Kinase M2, Pyruvate Dehydrogenase E1, Citrate synthase, Isocitrate Dehydrogenase 2, and Hypoxia Inducible Factor 1 Subunit Alpha. Conclusions: A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, Pyruvate Dehydrogenase Complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells. Combinational therapy approaches to block these pathways might be a promising and novel therapeutic strategy for targeting the metabolic requirements of AML cells.
{"title":"Glucose Metabolism in Acute Myeloid Leukemia Cell Line Is Regulated via Combinational PI3K/AKT/mTOR Pathway Inhibitors","authors":"Abbas Ranjbar, Mohsen Soltanshahi, Saeid Taghiloo, Hossein Asgarian-Omran","doi":"10.5812/ijpr-140507","DOIUrl":"https://doi.org/10.5812/ijpr-140507","url":null,"abstract":"Background: Metabolism reprogramming is a survival mechanism in acute myeloid leukemia (AML) cells in the tumor microenvironment. Therefore, we investigated the effect of signaling pathway inhibitors on the expression of genes rewired in the metabolic pathway of AML cells. Methods: HL-60 cells were treated with Idelalisib, MK-2206, and Everolimus, which respectively are selective inhibitors of phosphatidylinositol-3-kinase (PI3K), AKT, and the mammalian target of rapamycin (mTOR), either individually or in combination. The relative expressions of Glucose Transporter 1, Hexokinase 2, Pyruvate Kinase, Pyruvate Dehydrogenase E1, Citrate synthase, Isocitrate Dehydrogenase 2, and Hypoxia Inducible Factor 1 Subunit Alpha were determined by real-time PCR. Results: The combined treatment of HL-60 cells with Idelalisib, MK-2206, and Everolimus decreased the expression of Glucose Transporter 1, Hexokinase 2, Pyruvate Kinase M2, Pyruvate Dehydrogenase E1, Citrate synthase, Isocitrate Dehydrogenase 2, and Hypoxia Inducible Factor 1 Subunit Alpha. Conclusions: A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, Pyruvate Dehydrogenase Complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells. Combinational therapy approaches to block these pathways might be a promising and novel therapeutic strategy for targeting the metabolic requirements of AML cells.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"50 20","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134902809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Fatigue is one of the most prevalent symptoms, increasing worldwide with no specific medication for fatigue. Iranian traditional medicine (ITM), or Persian medicine, is a reliable source for discovering natural medicine for diseases and their symptoms. Myrtus communis L. (Myrtle), Malus domestica Borkh. (Apple), and Syzygium aromaticum (L.) Merr. & L. M. Perry (Clove) have been utilized as brain and heart tonics in ITM. Based on ITM, cardiac tonics decrease fatigue by enhancing heart function and increasing blood flow to tissues. These plants, particularly myrtle berries, have been utilized as potent enlivening agents that reduce mental fatigue. Objectives: This study aims to investigate the effects of aqueous extracts of these plants on weight-loaded forced swimming (WLFS) tests and three doses of aqueous myrtle extract in an animal model of chronic sleep deprivation-induced fatigue. Methods: Five groups of rats (n = 6) were evaluated: sham, control, apple-treated, clove-treated, and myrtle-treated groups. After 28 days of treatment, the WLFS test was performed, and swimming time was recorded. Subsequently, central fatigue was induced in rats by chronic sleep deprivation for 21 days. Five groups of rats (n = 6) were evaluated: sham, control (sleep-deprived, which received water), and three sleep-deprived + treatment groups, which received aqueous myrtle extract (350, 700, and 1000 mg/kg). An open field test on the 20th day and a WLFS test on the 21st day were performed. Results: The myrtle berries significantly increased glucose, reduced lactate dehydrogenase (LDH) levels, and enhanced swimming time. Fatigue caused by chronic sleep deprivation increased malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and LDH while decreased superoxide dismutase (SOD), glucose, and swimming time. In all treatment groups, SOD levels and swimming time were increased, whereas MDA, IL-1β, and TNF-α levels were decreased significantly. Only the 1000 mg/kg dose significantly reduced LDH levels (P < 0.001). The treatment significantly improved the velocity and the total distance moved in the open-field test. Conclusions: According to the results, the myrtle berries reduced fatigue in two animal models, probably due to its phenolic compounds, flavonoids, and polysaccharides.
背景:疲劳是最普遍的症状之一，在世界范围内增加，没有特定的药物治疗疲劳。伊朗传统医学(ITM)或波斯医学是发现治疗疾病及其症状的天然药物的可靠来源。桃金娘(Myrtus communis L.);(苹果)和Syzygium aromaticum (L.)稳定。,L. M. Perry(丁香)在ITM中被用作大脑和心脏的滋补品。根据ITM，心脏补药通过增强心脏功能和增加组织血流量来减少疲劳。这些植物，特别是桃金娘浆果，已经被用作有效的提神剂，减少精神疲劳。目的:本研究旨在探讨这些植物的水提取物对慢性睡眠剥夺性疲劳动物模型负重强迫游泳(WLFS)试验和三种剂量的桃金娘水提取物的影响。方法:将大鼠分为5组(n = 6):假手术组、对照组、苹果组、丁香组、桃金娘组。治疗28 d后进行WLFS试验，记录游泳时间。随后，慢性睡眠剥夺大鼠21天诱导中枢疲劳。评估五组大鼠(n = 6):假手术组、对照组(剥夺睡眠，给予水)和3个剥夺睡眠+治疗组，给予桃金娘水提取物(350、700和1000 mg/kg)。第20天进行野外试验，第21天进行WLFS试验。结果:桃金娘果实显著提高葡萄糖，降低乳酸脱氢酶(LDH)水平，延长游泳时间。慢性睡眠剥夺引起的疲劳增加丙二醛(MDA)、肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β)和LDH，降低超氧化物歧化酶(SOD)、葡萄糖和游泳时间。在所有治疗组中，SOD水平和游泳时间均升高，MDA、IL-1β和TNF-α水平均显著降低。只有1000mg /kg剂量显著降低LDH水平(P <0.001)。该处理显著提高了裸地试验中的速度和总移动距离。结论:桃金娘果实具有明显的抗疲劳作用，可能与桃金娘果实中的酚类化合物、黄酮类化合物和多糖有关。
{"title":"Antifatigue Effects of the Aqueous Extracts of Myrtle Berries, Apple and Clove: An Animal Study","authors":"Akram Alembagheri, Homa Hajimehdipour, Mona Khoramjouy, Somayeh Esmaeili, Mehrdad Faizi","doi":"10.5812/ijpr-140323","DOIUrl":"https://doi.org/10.5812/ijpr-140323","url":null,"abstract":"Background: Fatigue is one of the most prevalent symptoms, increasing worldwide with no specific medication for fatigue. Iranian traditional medicine (ITM), or Persian medicine, is a reliable source for discovering natural medicine for diseases and their symptoms. Myrtus communis L. (Myrtle), Malus domestica Borkh. (Apple), and Syzygium aromaticum (L.) Merr. & L. M. Perry (Clove) have been utilized as brain and heart tonics in ITM. Based on ITM, cardiac tonics decrease fatigue by enhancing heart function and increasing blood flow to tissues. These plants, particularly myrtle berries, have been utilized as potent enlivening agents that reduce mental fatigue. Objectives: This study aims to investigate the effects of aqueous extracts of these plants on weight-loaded forced swimming (WLFS) tests and three doses of aqueous myrtle extract in an animal model of chronic sleep deprivation-induced fatigue. Methods: Five groups of rats (n = 6) were evaluated: sham, control, apple-treated, clove-treated, and myrtle-treated groups. After 28 days of treatment, the WLFS test was performed, and swimming time was recorded. Subsequently, central fatigue was induced in rats by chronic sleep deprivation for 21 days. Five groups of rats (n = 6) were evaluated: sham, control (sleep-deprived, which received water), and three sleep-deprived + treatment groups, which received aqueous myrtle extract (350, 700, and 1000 mg/kg). An open field test on the 20th day and a WLFS test on the 21st day were performed. Results: The myrtle berries significantly increased glucose, reduced lactate dehydrogenase (LDH) levels, and enhanced swimming time. Fatigue caused by chronic sleep deprivation increased malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and LDH while decreased superoxide dismutase (SOD), glucose, and swimming time. In all treatment groups, SOD levels and swimming time were increased, whereas MDA, IL-1β, and TNF-α levels were decreased significantly. Only the 1000 mg/kg dose significantly reduced LDH levels (P < 0.001). The treatment significantly improved the velocity and the total distance moved in the open-field test. Conclusions: According to the results, the myrtle berries reduced fatigue in two animal models, probably due to its phenolic compounds, flavonoids, and polysaccharides.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135041799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Iman Ansari, Ezzatalsadat Hajiseid Javadi, Hamideh Pakniat, Ali Emami, Fatemeh Ranjkesh, Simindokht Molaverdikhani
Background: A significant number of pregnancies are at risk of threatened abortion (TA). Different types of progesterone are used to treat TA. Objectives: In this study, the effects of 2 forms of progesterone on the continuation of pregnancy and TA-caused pregnancy outcomes were compared. Methods: A total of 190 women with a gestational age of 6 - 13 weeks presenting with uterine bleeding, closed cervix, and absence of fetal heart rate diagnosed by vaginal examination and ultrasound were allocated into 2 groups and treated with either (D) dydrogesterone (10 mg twice a day) or (M) micronized progesterone (200 mg, twice a day) for beyond 2 weeks after the cessation of uterine bleeding to ensure that bleeding would not recur. The participants were followed up and received prenatal care until the end of pregnancy. The outcomes of pregnancy were recorded and compared between the 2 groups. Results: The incidence of preeclampsia, gestational diabetes, cesarean section, intrauterine fetal death (IUFD), placenta previa, and abortion was not significantly different between the 2 groups. However, the prevalence of preterm labor and low birth weight (LBW) was significantly lower in M-treated women (P < 0.001 and P = 0.007, respectively). The baby’s weight and gestational age at delivery were significantly higher in the M group than in the D group (P < 0.001). No serious drug side effects were observed in the 2 groups throughout the study. Conclusions: The results of this study showed that the incidence of preterm labor and LBW was significantly lower in the patients treated with micronized progesterone than in patients treated with dydrogesterone; however, the prevalence of preeclampsia, gestational diabetes, cesarean section, IUFD, and abortion was not significantly different between the 2 groups.
{"title":"Micronized Progesterone or Dydrogesterone? A Comparative Study on the Effects of Two Forms of Progesterone on Pregnancy Outcomes After Threatened Abortion","authors":"Iman Ansari, Ezzatalsadat Hajiseid Javadi, Hamideh Pakniat, Ali Emami, Fatemeh Ranjkesh, Simindokht Molaverdikhani","doi":"10.5812/ijpr-136320","DOIUrl":"https://doi.org/10.5812/ijpr-136320","url":null,"abstract":"Background: A significant number of pregnancies are at risk of threatened abortion (TA). Different types of progesterone are used to treat TA. Objectives: In this study, the effects of 2 forms of progesterone on the continuation of pregnancy and TA-caused pregnancy outcomes were compared. Methods: A total of 190 women with a gestational age of 6 - 13 weeks presenting with uterine bleeding, closed cervix, and absence of fetal heart rate diagnosed by vaginal examination and ultrasound were allocated into 2 groups and treated with either (D) dydrogesterone (10 mg twice a day) or (M) micronized progesterone (200 mg, twice a day) for beyond 2 weeks after the cessation of uterine bleeding to ensure that bleeding would not recur. The participants were followed up and received prenatal care until the end of pregnancy. The outcomes of pregnancy were recorded and compared between the 2 groups. Results: The incidence of preeclampsia, gestational diabetes, cesarean section, intrauterine fetal death (IUFD), placenta previa, and abortion was not significantly different between the 2 groups. However, the prevalence of preterm labor and low birth weight (LBW) was significantly lower in M-treated women (P < 0.001 and P = 0.007, respectively). The baby’s weight and gestational age at delivery were significantly higher in the M group than in the D group (P < 0.001). No serious drug side effects were observed in the 2 groups throughout the study. Conclusions: The results of this study showed that the incidence of preterm labor and LBW was significantly lower in the patients treated with micronized progesterone than in patients treated with dydrogesterone; however, the prevalence of preeclampsia, gestational diabetes, cesarean section, IUFD, and abortion was not significantly different between the 2 groups.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"45 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135042607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Two mangostin compounds, gamma-mangostin and alpha-mangostin, show anticancer properties through the inhibition of cell proliferation and cell migration. Metastatic triple-negative breast cancer (TNBC) cells, including MDA-MB-231, highly express C-X-C chemokine receptor type 4 (CXCR4) to maintain reactive oxygen species (ROS) and cell migration. Objectives: This study was performed to analyze and compare different modes of action of γ-mangostin and α-mangostin as antimigratory effects targeted on CXCR4 in MDA-MB-231 as a model of TNBC cell. Methods: This study investigated the effect of γ-mangostin and α-mangostin using a series of assays, including Cell Counting Kit-8 (CCK-8) assay for cytotoxicity, wound healing assay for migration study, quantitative real-time polymerase chain reaction (qRT-PCR) for gene expression analysis, and flow cytometry for ROS measurement, along with in silico study to observe the binding between the compound and CXCR4. Results: The findings revealed half maximal inhibitory concentration (IC50) values of 25 and 20 μM for γ-mangostin and α-mangostin in MDA-MB 231 cells, respectively. Moreover, a concentration of 10 μM was used for the migration assay. Both γ-mangostin and α-mangostin significantly suppressed cell migration within 24 hours. The present gene expression studies revealed the downregulation of key migration-associated genes, namely Farp, CXCR4, and LPHN2, upon γ-mangostin treatment but not α-mangostin. Additionally, both γ-mangostin and α-mangostin increased cellular ROS generation, highlighting the same effect of γ-mangostin and α-mangostin ROS elevation to inhibit cancer cell migration. Molecular docking simulations further suggested a potential interaction between γ-mangostin and α-mangostin with CXCR4 in high affinity. Conclusions: These findings suggest that both γ-mangostin and α-mangostin inhibit breast cancer cell migration and induce cellular ROS levels in MDA-MB-231 cells; notably, γ-mangostin suppresses CXCR4 mRNA expression that might correlate to its activity to inhibit MDA-MB-231 cell migration.
{"title":"Different Modes of Mechanism of Gamma-Mangostin and Alpha-Mangostin to Inhibit Cell Migration of Triple-Negative Breast Cancer Cells Concerning CXCR4 Downregulation and ROS Generation","authors":"Sarmoko Sarmoko, Dhania Novitasari, Manami Toriyama, Muhamad Salman Fareza, N.A Choironi, Hiroshi Itoh, Edy Meiyanto","doi":"10.5812/ijpr-138856","DOIUrl":"https://doi.org/10.5812/ijpr-138856","url":null,"abstract":"Background: Two mangostin compounds, gamma-mangostin and alpha-mangostin, show anticancer properties through the inhibition of cell proliferation and cell migration. Metastatic triple-negative breast cancer (TNBC) cells, including MDA-MB-231, highly express C-X-C chemokine receptor type 4 (CXCR4) to maintain reactive oxygen species (ROS) and cell migration. Objectives: This study was performed to analyze and compare different modes of action of γ-mangostin and α-mangostin as antimigratory effects targeted on CXCR4 in MDA-MB-231 as a model of TNBC cell. Methods: This study investigated the effect of γ-mangostin and α-mangostin using a series of assays, including Cell Counting Kit-8 (CCK-8) assay for cytotoxicity, wound healing assay for migration study, quantitative real-time polymerase chain reaction (qRT-PCR) for gene expression analysis, and flow cytometry for ROS measurement, along with in silico study to observe the binding between the compound and CXCR4. Results: The findings revealed half maximal inhibitory concentration (IC50) values of 25 and 20 μM for γ-mangostin and α-mangostin in MDA-MB 231 cells, respectively. Moreover, a concentration of 10 μM was used for the migration assay. Both γ-mangostin and α-mangostin significantly suppressed cell migration within 24 hours. The present gene expression studies revealed the downregulation of key migration-associated genes, namely Farp, CXCR4, and LPHN2, upon γ-mangostin treatment but not α-mangostin. Additionally, both γ-mangostin and α-mangostin increased cellular ROS generation, highlighting the same effect of γ-mangostin and α-mangostin ROS elevation to inhibit cancer cell migration. Molecular docking simulations further suggested a potential interaction between γ-mangostin and α-mangostin with CXCR4 in high affinity. Conclusions: These findings suggest that both γ-mangostin and α-mangostin inhibit breast cancer cell migration and induce cellular ROS levels in MDA-MB-231 cells; notably, γ-mangostin suppresses CXCR4 mRNA expression that might correlate to its activity to inhibit MDA-MB-231 cell migration.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"76 16","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135092841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Overactive bladder (OAB) is a symptomatic condition characterized by urinary urgency with or without incontinence, usually associated with frequent daytime urination, enuresis, and nocturia. Objectives: This economic evaluation was aimed at assessing the cost-effectiveness of mirabegron versus solifenacin in the treatment of OAB patients from a payer’s perspective in Iran. Methods: A Markov model with a 5-year time horizon was used. The model consisted of five health states, and OAB patients with an average age of 60 years entered the cycle from the persistent state. Transition probabilities were based on published trials, clinical judgments, and expert opinions. Resource use and costs, including those for medications and adverse events, were extracted from the literature and tariff book, and all costs are presented in 2019 US dollars with a 5% discount rate for the costs and utilities. The incremental cost-effectiveness ratio (ICER) and quality-adjusted life-years (QALYs) were computed for medications, and sensitivity analyses were used to test the robustness of the results. Results: Average per-patient treatment costs were $24,720.7 and $24,668.6 for mirabegron and solifenacin, respectively. Mirabegron was expected to produce higher QALYs than solifenacin (3.20 vs. 3.19). Mirabegron had an ICER of $531.3 over solifenacin, lower than the willingness-to-pay (WTP) threshold. The probabilistic analysis showed mirabegron cost-effectiveness in 80% of simulations at the WTP of $2709/QALY. Conclusions: Compared to solifenacin, mirabegron was more cost-effective in OAB patients in the Iranian healthcare system.
背景:膀胱过动症(OAB)是一种以尿急伴或不伴尿失禁为特征的症状性疾病，通常伴有频繁的日间排尿、遗尿和夜尿症。目的:本经济评价旨在从伊朗支付方的角度评估mirabegron与solifenacin治疗OAB患者的成本效益。方法:采用5年时间跨度的马尔可夫模型。模型由5种健康状态组成，平均年龄为60岁的OAB患者从持续状态进入周期。转移概率基于已发表的试验、临床判断和专家意见。资源使用和成本，包括药物和不良事件的成本，摘自文献和关税手册，所有成本均以2019年美元表示，成本和公用事业的折扣率为5%。计算药物的增量成本-效果比(ICER)和质量调整生命年(QALYs)，并采用敏感性分析来检验结果的稳健性。结果:mirabegron和solifenacin的平均每位患者治疗费用分别为24,720.7美元和24,668.6美元。Mirabegron预期比索利那新产生更高的QALYs (3.20 vs 3.19)。Mirabegron的ICER比solifenacin的ICER为531.3美元，低于支付意愿(WTP)阈值。概率分析显示，在WTP为2709美元/QALY时，mirabegron在80%的模拟中具有成本效益。结论:与索利那新相比，mirabegron在伊朗医疗系统中对OAB患者更具成本效益。
{"title":"Cost-Utility Analysis of Mirabegron Compared to Solifenacin in the Treatment of Overactive Bladder (OAB) in Iran","authors":"Zahra Karimi Majd, Ghader Mohammadnezhad, Saeed Taheri, Nazila Yousefi","doi":"10.5812/ijpr-136447","DOIUrl":"https://doi.org/10.5812/ijpr-136447","url":null,"abstract":"Background: Overactive bladder (OAB) is a symptomatic condition characterized by urinary urgency with or without incontinence, usually associated with frequent daytime urination, enuresis, and nocturia. Objectives: This economic evaluation was aimed at assessing the cost-effectiveness of mirabegron versus solifenacin in the treatment of OAB patients from a payer’s perspective in Iran. Methods: A Markov model with a 5-year time horizon was used. The model consisted of five health states, and OAB patients with an average age of 60 years entered the cycle from the persistent state. Transition probabilities were based on published trials, clinical judgments, and expert opinions. Resource use and costs, including those for medications and adverse events, were extracted from the literature and tariff book, and all costs are presented in 2019 US dollars with a 5% discount rate for the costs and utilities. The incremental cost-effectiveness ratio (ICER) and quality-adjusted life-years (QALYs) were computed for medications, and sensitivity analyses were used to test the robustness of the results. Results: Average per-patient treatment costs were $24,720.7 and $24,668.6 for mirabegron and solifenacin, respectively. Mirabegron was expected to produce higher QALYs than solifenacin (3.20 vs. 3.19). Mirabegron had an ICER of $531.3 over solifenacin, lower than the willingness-to-pay (WTP) threshold. The probabilistic analysis showed mirabegron cost-effectiveness in 80% of simulations at the WTP of $2709/QALY. Conclusions: Compared to solifenacin, mirabegron was more cost-effective in OAB patients in the Iranian healthcare system.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 17","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135390778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jin Ma, Cong Wang, Tieying Yin, Yang Jiang, Wanjun Yu, Xiaoyu Zhang, Qin Qin, Hua Yang, Dechuan Zhang
Background: Hemorrhage control and anti-infection play a crucial role in promoting wound healing in trauma-related injuries. Objectives: This study aimed to prepare nanoparticles with dual functions of hemostasis and antibacterial properties. Methods: The dual-functional nanoparticles (CDCA-PLL NPs) were developed using a self-assembly method based on the electrostatic forces between Poly-L-lysine (PLL) and Chenodeoxycholic acid (CDCA). The physicochemical properties, hemostatic properties, and antibacterial activities were investigated. Results: The prepared nanoparticles displayed a spherical structure, exhibiting a high drug loading capacity, encapsulation efficiency, and good stability. The CDCA-PLL NPs could reduce the hemolysis caused by PLL and promote the proliferation of human fibroblasts, indicating excellent biosafety. Moreover, CDCA-PLL NPs demonstrated a shorter in vivo hemostasis time and reduced blood loss in mouse tail vein hemorrhage, femoral vein hemorrhage, femoral artery hemorrhage, and liver hemorrhage models. Also, CDCA-PLL NPs showed excellent antibacterial efficacy against E. coli and S. aureus. Conclusions: CDCA-PLL NPs have great potential to be extensively applied as a hemostatic and antibacterial agent in various clinical conditions.
{"title":"Preparation and in Vitro Property Research of Cholic Acid Nanoparticles with Dual Functions of Hemostasis and Antibacterial","authors":"Jin Ma, Cong Wang, Tieying Yin, Yang Jiang, Wanjun Yu, Xiaoyu Zhang, Qin Qin, Hua Yang, Dechuan Zhang","doi":"10.5812/ijpr-135437","DOIUrl":"https://doi.org/10.5812/ijpr-135437","url":null,"abstract":"Background: Hemorrhage control and anti-infection play a crucial role in promoting wound healing in trauma-related injuries. Objectives: This study aimed to prepare nanoparticles with dual functions of hemostasis and antibacterial properties. Methods: The dual-functional nanoparticles (CDCA-PLL NPs) were developed using a self-assembly method based on the electrostatic forces between Poly-L-lysine (PLL) and Chenodeoxycholic acid (CDCA). The physicochemical properties, hemostatic properties, and antibacterial activities were investigated. Results: The prepared nanoparticles displayed a spherical structure, exhibiting a high drug loading capacity, encapsulation efficiency, and good stability. The CDCA-PLL NPs could reduce the hemolysis caused by PLL and promote the proliferation of human fibroblasts, indicating excellent biosafety. Moreover, CDCA-PLL NPs demonstrated a shorter in vivo hemostasis time and reduced blood loss in mouse tail vein hemorrhage, femoral vein hemorrhage, femoral artery hemorrhage, and liver hemorrhage models. Also, CDCA-PLL NPs showed excellent antibacterial efficacy against E. coli and S. aureus. Conclusions: CDCA-PLL NPs have great potential to be extensively applied as a hemostatic and antibacterial agent in various clinical conditions.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"66 10","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135863165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Setayesh Sadeghi, Fatemeh Mohammadian, Mehdi Tehrani-Doost, Kheirollah Gholami, Niayesh Mohebbi
Background: Decision-making is a complex process, and most studies showed that patients with mild cognitive impairment (MCI) make worse decisions than healthy people. Objectives: This study aims to evaluate the effect of rivastigmine on the decision-making of MCI patients using the Cambridge Neuropsychological Test Automated Battery (CANTAB) tests. Methods: The study was conducted at the Roozbeh Hospital neurology clinic, and 30 patients with mild cognitive impairment over 40 years old were randomly recruited to receive rivastigmine or placebo twice daily for 12 weeks. The initial dose of rivastigmine or placebo was 1.5 mg twice daily and was increased to 3 mg twice daily per patient compliance. A CANTAB test was conducted before and following the intervention. Results: The mean age of patients in the rivastigmine group was 58.93 ± 10.88, and in the placebo group was 59.33 ± 10.34. The median MMSE (Mini-Mental State Examination) was 26 (IQR = 25 - 26) in both groups. Patients in the rivastigmine group showed significant differences in all subgroup tests of CGT, IST, and SST except in risk adjustment in the CGT test, discrimination in the IST test, and median correct RT on the go trial and SSRT in the SST test. The most commonly reported adverse effects were gastrointestinal complications. Conclusions: According to the results, rivastigmine significantly improved the primary decision-making outcomes in comparison with placebo.
背景:决策是一个复杂的过程，大多数研究表明轻度认知障碍(MCI)患者的决策比健康人更差。目的:采用剑桥神经心理测试自动化电池(CANTAB)测试，评价利瓦斯汀对MCI患者决策的影响。方法:研究在Roozbeh医院神经病学门诊进行，随机招募30例40岁以上轻度认知障碍患者，每天2次接受瑞瓦斯替明或安慰剂治疗，持续12周。利瓦斯汀或安慰剂的初始剂量为1.5 mg，每日两次，并增加至3mg，每日两次。在干预前后分别进行了CANTAB测试。结果:利瓦斯汀组患者平均年龄为58.93±10.88岁，安慰剂组患者平均年龄为59.33±10.34岁。两组的中位MMSE (Mini-Mental State Examination)均为26 (IQR = 25 - 26)。利瓦斯汀组患者在CGT、IST和SST的所有亚组测试中，除了CGT测试的风险调整、IST测试的区分、go试验的中位正确RT和SST测试的中位正确RT外，其他亚组测试均存在显著差异。最常见的不良反应是胃肠道并发症。结论:结果显示，与安慰剂相比，利瓦斯汀可显著改善患者的主要决策结局。
{"title":"Evaluating the Effects of Rivastigmine on Decision-Making in Patients with Mild Cognitive Impairment by Cambridge Neuropsychological Test Automated Battery (CANTAB); A Randomized, Double-Blind, Placebo-Controlled Trial","authors":"Setayesh Sadeghi, Fatemeh Mohammadian, Mehdi Tehrani-Doost, Kheirollah Gholami, Niayesh Mohebbi","doi":"10.5812/ijpr-138943","DOIUrl":"https://doi.org/10.5812/ijpr-138943","url":null,"abstract":"Background: Decision-making is a complex process, and most studies showed that patients with mild cognitive impairment (MCI) make worse decisions than healthy people. Objectives: This study aims to evaluate the effect of rivastigmine on the decision-making of MCI patients using the Cambridge Neuropsychological Test Automated Battery (CANTAB) tests. Methods: The study was conducted at the Roozbeh Hospital neurology clinic, and 30 patients with mild cognitive impairment over 40 years old were randomly recruited to receive rivastigmine or placebo twice daily for 12 weeks. The initial dose of rivastigmine or placebo was 1.5 mg twice daily and was increased to 3 mg twice daily per patient compliance. A CANTAB test was conducted before and following the intervention. Results: The mean age of patients in the rivastigmine group was 58.93 ± 10.88, and in the placebo group was 59.33 ± 10.34. The median MMSE (Mini-Mental State Examination) was 26 (IQR = 25 - 26) in both groups. Patients in the rivastigmine group showed significant differences in all subgroup tests of CGT, IST, and SST except in risk adjustment in the CGT test, discrimination in the IST test, and median correct RT on the go trial and SSRT in the SST test. The most commonly reported adverse effects were gastrointestinal complications. Conclusions: According to the results, rivastigmine significantly improved the primary decision-making outcomes in comparison with placebo.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"73 12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136067942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: Epilepsy, as a neurological disease, can be defined as frequent seizure attacks. Further, it affects many other aspects of patients’ mental activities, such as learning and memory. Scorpion venoms have gained notice as compounds with potential antiepileptic properties. Among them, Buthotus schach (BS) is one of the Iranian scorpions studied by Aboutorabi et al., who fractionated, characterized, and tested this compound using electrophysiological techniques in brain slices (patch-clamp recording). In the present study, the fraction obtained from gel electrophoresis was investigated through behavioral and electrophysiological assays. At first, ventricular cannulation was performed in rats, and then the active fraction (i.e., F3), carbamazepine, and the vehicle were microinjected into the brain before seizure induction by the subcutaneous (SC) injection of pentylenetetrazol (PTZ). Seizure behaviors were scaled according to Racine stages. Memory and learning were evaluated using the Y-maze and passive avoidance tests. Other groups entered evoked field potential recording after microinjection and seizure induction. Population spike (PS) and field excitatory postsynaptic potential (fEPSP) were measured. The F3 fraction could prevent the fifth stage and postpone the third stage of seizure compared to the control (carbamazepine) group. There was no significant improvement in memory and learning in the group treated with the F3 fraction. Also, PS amplitude increased significantly, and long-term potentiation was successfully formed after the high-frequency stimulation of the performant pathway. Our results support the antiepileptic effects of the F3 fraction of BS venom, evidenced by behavioral and electrophysiological studies. However, the effects of this fraction on memory and learning were not in the same direction, suggesting the involvement of two different pathways.
{"title":"The Effects of the Fraction Isolated from Iranian Buthotus shach Scorpion Venom on Synaptic Plasticity, Learning, Memory, and Seizure Susceptibility","authors":"Elmira Heidarli, Hossein Vatanpour, Nafiseh Nasrabadi, Maha Soltani, Saeed Tahmasebi, Mehrdad Faizi","doi":"10.5812/ijpr-138273","DOIUrl":"https://doi.org/10.5812/ijpr-138273","url":null,"abstract":": Epilepsy, as a neurological disease, can be defined as frequent seizure attacks. Further, it affects many other aspects of patients’ mental activities, such as learning and memory. Scorpion venoms have gained notice as compounds with potential antiepileptic properties. Among them, Buthotus schach (BS) is one of the Iranian scorpions studied by Aboutorabi et al., who fractionated, characterized, and tested this compound using electrophysiological techniques in brain slices (patch-clamp recording). In the present study, the fraction obtained from gel electrophoresis was investigated through behavioral and electrophysiological assays. At first, ventricular cannulation was performed in rats, and then the active fraction (i.e., F3), carbamazepine, and the vehicle were microinjected into the brain before seizure induction by the subcutaneous (SC) injection of pentylenetetrazol (PTZ). Seizure behaviors were scaled according to Racine stages. Memory and learning were evaluated using the Y-maze and passive avoidance tests. Other groups entered evoked field potential recording after microinjection and seizure induction. Population spike (PS) and field excitatory postsynaptic potential (fEPSP) were measured. The F3 fraction could prevent the fifth stage and postpone the third stage of seizure compared to the control (carbamazepine) group. There was no significant improvement in memory and learning in the group treated with the F3 fraction. Also, PS amplitude increased significantly, and long-term potentiation was successfully formed after the high-frequency stimulation of the performant pathway. Our results support the antiepileptic effects of the F3 fraction of BS venom, evidenced by behavioral and electrophysiological studies. However, the effects of this fraction on memory and learning were not in the same direction, suggesting the involvement of two different pathways.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"227 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136103450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ali Honarpardaz, Morteza Daliri Joupari, Sajjad Tavakkoli
Background: Tissue engineering is the application system that tries to restore damaged tissues by different approaches, such as cellular therapy, application of cell differential factors, and various materials. One of the important goals in tissue engineering is to guide stem cells directly to the desired tissue, and researchers tried to utilize different molecules as effective factors to improve this technique. Objectives: This study aims to demonstrate the effects of diacerein, a slow-acting drug for the treatment of osteoarthritis, on mesenchymal stem cell proliferation and evaluate its potential in the chondrogenesis process. Methods: Stem cells were isolated from adipose tissue, characterized by flow cytometry, and cells were treated with 10-5M diacerein for three weeks. Chondrogenic gene expression of SOX9, COL2A1, ACAN, and TGFB1 were analyzed by qRT-PCR and immunocytochemistry techniques. Results: Our results showed that diacerein increased the expression of the following genes involved in chondrogenesis: SOX9 (2.9-fold, P < 0.00), COL2A1 (2.2-fold, P < 0.00), ACAN (2.7-fold, P < 0.00), and TGFB1 (2.6-fold, P < 0.00). Immunocytochemistry results also showed increased production of collagen type II as the main protein marker for chondrocytes. Conclusions: We observed that diacerein alone could initiate and enhance chondrogenesis, and it can be used as a differentiation factor for stem cells to chondrocyte besides its ability to inhibit IL-1β. Knowing the actual function of diacerein, it could be a good candidate for the treatment of osteoarthritis.
{"title":"In Vitro Chondrogenic Differentiation of Human Adipose-Derived Stem Cells by Diacerein","authors":"Ali Honarpardaz, Morteza Daliri Joupari, Sajjad Tavakkoli","doi":"10.5812/ijpr-137803","DOIUrl":"https://doi.org/10.5812/ijpr-137803","url":null,"abstract":"Background: Tissue engineering is the application system that tries to restore damaged tissues by different approaches, such as cellular therapy, application of cell differential factors, and various materials. One of the important goals in tissue engineering is to guide stem cells directly to the desired tissue, and researchers tried to utilize different molecules as effective factors to improve this technique. Objectives: This study aims to demonstrate the effects of diacerein, a slow-acting drug for the treatment of osteoarthritis, on mesenchymal stem cell proliferation and evaluate its potential in the chondrogenesis process. Methods: Stem cells were isolated from adipose tissue, characterized by flow cytometry, and cells were treated with 10-5M diacerein for three weeks. Chondrogenic gene expression of SOX9, COL2A1, ACAN, and TGFB1 were analyzed by qRT-PCR and immunocytochemistry techniques. Results: Our results showed that diacerein increased the expression of the following genes involved in chondrogenesis: SOX9 (2.9-fold, P < 0.00), COL2A1 (2.2-fold, P < 0.00), ACAN (2.7-fold, P < 0.00), and TGFB1 (2.6-fold, P < 0.00). Immunocytochemistry results also showed increased production of collagen type II as the main protein marker for chondrocytes. Conclusions: We observed that diacerein alone could initiate and enhance chondrogenesis, and it can be used as a differentiation factor for stem cells to chondrocyte besides its ability to inhibit IL-1β. Knowing the actual function of diacerein, it could be a good candidate for the treatment of osteoarthritis.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"5 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136159411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammad Reza Khalilian, Fariba Esmaeili, Mohamad Reza Vahidi, Mohsen Rouzrokh, Elham Abdoulahzadeh, Hadi Pashapour, Mohammad Ghazavi
: Hemangiomas are benign vascular tumors that often develop in infants. The most common treatment option for complicated hemangiomas is propranolol. We discuss the use of oral propranolol in treating infantile hemangioma (IH) in an Iranian population at our hospital. We conducted a cross-sectional prospective descriptive study on 62 infants aged 1 to 16 months from 2017 to 2021. Propranolol was gradually administered orally at a dose of 3 mg/kg/day. The hemangioma score was examined at 6 intervals (first visit, 1, 3, 6, 9, and 12 months later). Propranolol therapies were stopped when there was no further decrease in scores for 2 successive visits. The study was completed by 62 patients. In terms of hemangiomas, 46 (74.2%) patients had 1 lesion, 12 (19.4%) had 2 lesions, and 4 (6.5%) had 3 lesions. Over time, the average size of hemangiomas steadily decreased, such that 5 patients (9.1%) were completely treated; 1 patient improved after 3 months, 3 after 6 months, 1 after 9 months, and 57 (91.9%) were partially treated. Aside from being safe and effective, propanol can also obtain a higher response rate when treatment is started early in infants aged less than 3 months.
{"title":"The Efficacy and Safety of Propranolol in Treating Infantile Hemangioma: A Prospective Study","authors":"Mohammad Reza Khalilian, Fariba Esmaeili, Mohamad Reza Vahidi, Mohsen Rouzrokh, Elham Abdoulahzadeh, Hadi Pashapour, Mohammad Ghazavi","doi":"10.5812/ijpr-135140","DOIUrl":"https://doi.org/10.5812/ijpr-135140","url":null,"abstract":": Hemangiomas are benign vascular tumors that often develop in infants. The most common treatment option for complicated hemangiomas is propranolol. We discuss the use of oral propranolol in treating infantile hemangioma (IH) in an Iranian population at our hospital. We conducted a cross-sectional prospective descriptive study on 62 infants aged 1 to 16 months from 2017 to 2021. Propranolol was gradually administered orally at a dose of 3 mg/kg/day. The hemangioma score was examined at 6 intervals (first visit, 1, 3, 6, 9, and 12 months later). Propranolol therapies were stopped when there was no further decrease in scores for 2 successive visits. The study was completed by 62 patients. In terms of hemangiomas, 46 (74.2%) patients had 1 lesion, 12 (19.4%) had 2 lesions, and 4 (6.5%) had 3 lesions. Over time, the average size of hemangiomas steadily decreased, such that 5 patients (9.1%) were completely treated; 1 patient improved after 3 months, 3 after 6 months, 1 after 9 months, and 57 (91.9%) were partially treated. Aside from being safe and effective, propanol can also obtain a higher response rate when treatment is started early in infants aged less than 3 months.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"40 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135803279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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