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Chitosan and Its Structural Modifications for siRNA Delivery. 壳聚糖及其用于siRNA递送的结构修饰。
IF 3.6 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-01 DOI: 10.34172/apb.2023.030
Mona Y Al-Absi, Anna Eleonora Caprifico, Gianpiero Calabrese

The use of RNA interference mechanism and small interfering RNA (siRNA) in cancer gene therapy is a very promising approach. However, the success of gene silencing is underpinned by the efficient delivery of intact siRNA into the targeted cell. Nowadays, chitosan is one of the most widely studied non-viral vectors for siRNA delivery, since it is a biodegradable, biocompatible and positively charged polymer able to bind to the negatively charged siRNA forming nanoparticles (NPs) that will act as siRNA delivery system. However, chitosan shows several limitations such as low transfection efficiency and low solubility at physiological pH. Therefore, a variety of chemical and non-chemical structural modifications of chitosan were investigated in the attempt to develop a chitosan derivative showing the features of an ideal siRNA carrier. In this review, the most recently proposed chemical modifications of chitosan are outlined. The type of modification, chemical structure, physicochemical properties, siRNA binding affinity and complexation efficiency of the modified chitosan are discussed. Moreover, the resulting NPs characteristics, cellular uptake, serum stability, cytotoxicity and gene transfection efficiency in vitro and/or in vivo are described and compared to the unmodified chitosan. Finally, a critical analysis of a selection of modifications is included, highlighting the most promising ones for this purpose in the future.

利用RNA干扰机制和小干扰RNA (siRNA)进行肿瘤基因治疗是一种很有前景的方法。然而,基因沉默的成功是由完整的siRNA有效地传递到目标细胞的基础上的。壳聚糖是一种可生物降解的、具有生物相容性的、带正电荷的聚合物,能够与带负电荷的siRNA结合形成纳米颗粒(NPs),作为siRNA递送系统,是目前研究最广泛的siRNA非病毒载体之一。然而,壳聚糖存在转染效率低、生理ph下溶解度低等局限性。因此,研究了壳聚糖的多种化学和非化学结构修饰,试图开发出具有理想siRNA载体特征的壳聚糖衍生物。本文综述了最近提出的壳聚糖化学改性方法。讨论了改性壳聚糖的改性类型、化学结构、理化性质、siRNA结合亲和力和络合效率。此外,所得到的NPs特性、细胞摄取、血清稳定性、细胞毒性和基因转染效率在体外和/或体内进行了描述,并与未修饰的壳聚糖进行了比较。最后,对选择的修改进行了批判性分析,突出了未来最有希望实现这一目的的修改。
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引用次数: 1
Iron Withdrawal with DIBI, a Novel 3-Hydroxypyridin-4-One Chelator Iron-Binding Polymer, Attenuates Macrophage Inflammatory Responses. DIBI是一种新型的3-羟基吡啶-4- 1螯合剂铁结合聚合物,它可以减轻巨噬细胞的炎症反应。
IF 3.6 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-01 DOI: 10.34172/apb.2023.040
Javad Ghassemi-Rad, Wasundara Fernando, Bruce E Holbein, David W Hoskin

Purpose: Iron is an essential trace element for the inflammatory response to infection. In this study, we determined the effect of the recently developed iron-binding polymer DIBI on the synthesis of inflammatory mediators by RAW 264.7 macrophages and bone marrow-derived macrophages (BMDMs) in response to lipopolysaccharide (LPS) stimulation. Methods: Flow cytometry was used to determine the intracellular labile iron pool, reactive oxygen species production, and cell viability. Cytokine production was measured by quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Nitric oxide synthesis was determined by the Griess assay. Western blotting was used to assess signal transducer and activator of transcription (STAT) phosphorylation. Results: Macrophages cultured in the presence of DIBI exhibited a rapid and significant reduction in their intracellular labile iron pool. DIBI-treated macrophages showed reduced expression of proinflammatory cytokines interferon-β, interleukin (IL)-1β, and IL-6 in response to LPS. In contrast, exposure to DIBI did not affect LPS-induced expression of tumor necrosis factor-α (TNF-α). The inhibitory effect of DIBI on IL-6 synthesis by LPS-stimulated macrophages was lost when exogenous iron in the form of ferric citrate was added to culture, confirming the selectivity of DIBI for iron. DIBI-treated macrophages showed reduced production of reactive oxygen species and nitric oxide following LPS stimulation. DIBI-treated macrophages also showed a reduction in cytokine-induced activation of STAT 1 and 3, which potentiate LPS-induced inflammatory responses. Conclusion: DIBI-mediated iron withdrawal may be able to blunt the excessive inflammatory response by macrophages in conditions such as systemic inflammatory syndrome.

目的:铁是一种必需的微量元素对感染的炎症反应。在这项研究中,我们确定了最近开发的铁结合聚合物DIBI对RAW 264.7巨噬细胞和骨髓源性巨噬细胞(bmdm)在脂多糖(LPS)刺激下合成炎症介质的影响。方法:采用流式细胞术检测细胞内不稳定铁池、活性氧生成及细胞活力。采用定量逆转录聚合酶链反应和酶联免疫吸附法测定细胞因子的产生。用Griess法测定一氧化氮的合成。Western blotting检测信号转导因子和转录激活因子(STAT)磷酸化。结果:在DIBI存在下培养的巨噬细胞显示出细胞内不稳定铁池的快速和显著减少。dibi处理的巨噬细胞对LPS的反应显示促炎细胞因子干扰素-β、白细胞介素(IL)-1β和IL-6的表达降低。相反,暴露于DIBI不影响lps诱导的肿瘤坏死因子-α (TNF-α)的表达。当向培养物中加入柠檬酸铁形式的外源铁时,DIBI对lps刺激的巨噬细胞合成IL-6的抑制作用消失,证实了DIBI对铁的选择性。LPS刺激后,dibi处理的巨噬细胞显示活性氧和一氧化氮的产生减少。dibi处理的巨噬细胞也显示细胞因子诱导的STAT 1和3激活减少,STAT 1和3增强了lps诱导的炎症反应。结论:dibi介导的铁戒断可能能够减弱全身炎症综合征等疾病中巨噬细胞的过度炎症反应。
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引用次数: 0
Electrosprayed Nanoparticles Containing Hydroalcoholic Extract of Echinacea purpurea (L.) Moench Stimulates Immune System by Increasing Inflammatory Factors in Male Wistar Rats. 紫锥菊水醇提取物电喷涂纳米颗粒Moench通过增加雄性Wistar大鼠的炎症因子刺激免疫系统。
IF 3.6 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-01 DOI: 10.34172/apb.2023.031
Fatemeh Mehdizadeh, Ramin Mohammadzadeh, Hossein Nazemiyeh, Mehran Mesgari-Abbasi, Mohammad Barzegar-Jalali, Morteza Eskandani, Khosro Adibkia

Purpose: Echinacea purpurea (L.) Moench is a member of the Asteraceae family and is traditionally used mainly due to its immunostimulatory properties. Various compounds including alkylamides and chicoric acid were reported as active ingredients of E. purpurea. Here, we aimed to prepare electrosprayed nanoparticles (NPs) containing hydroalcoholic extract of E. purpurea using Eudragit RS100 (EP-Eudragit RS100 NPs) to improve the immunomodulatory effects of the extract. Methods: The EP-Eudragit RS100 NPs with the different extract:polymer ratios and solution concentrations were prepared using the electrospray technique. The size and morphology of the NPs were evaluated using dynamic light scattering (DLS) and field emission-scanning electron microscopy (FE-SEM). To evaluate the immune responses, male Wistar rats were administrated with the prepared EP-Eudragit RS100 NPs and plain extract in the final dose of 30 or 100 mg/kg. The blood samples of the animals were collected and the inflammatory factors and complete blood count (CBC) were investigated. Results: In vivo studies indicated that the plain extract and EP-Eudragit RS100 NPs (100 mg/kg) significantly increased the serum level of tumor necrosis factor-α (TNF-α) and interleukin 1-β (IL1-β) whereas the EP-Eudragit RS100 NPs (30 mg/kg) significantly increased the number of white blood cells (WBCs) compared to the control group. Lymphocytes' count in all groups was increased significantly compared to the control group (P<0.05) whereas other CBC parameters remained unchanged. Conclusion: The prepared EP-Eudragit RS100 NPs by electrospray technique caused significant reinforcement in the immunostimulatory effects of the extract of E. purpurea.

目的:紫锥菊(L.)牡丹是一种菊科植物,传统上主要是由于其免疫刺激特性而被使用。各种化合物包括烷基酰胺和菊苣酸被报道为紫荆的有效成分。本实验以紫荆草RS100 (EP-Eudragit RS100 NPs)为材料,制备含有紫荆草水醇提取物的电喷涂纳米颗粒(NPs),以提高紫荆草水醇提取物的免疫调节作用。方法:采用电喷雾技术制备不同萃取物与聚合物比例和溶液浓度的EP-Eudragit RS100 NPs。采用动态光散射(DLS)和场发射扫描电镜(FE-SEM)对NPs的大小和形貌进行了评价。为了评价免疫应答,雄性Wistar大鼠分别以30或100 mg/kg的终剂量给药制备的EP-Eudragit RS100 NPs和纯提取物。采集动物血液,检测炎症因子和全血细胞计数(CBC)。结果:体内研究表明,与对照组相比,平提物和EP-Eudragit RS100 NPs (100 mg/kg)显著提高了血清肿瘤坏死因子-α (TNF-α)和白细胞介素1-β (il - 1-β)水平,EP-Eudragit RS100 NPs (30 mg/kg)显著增加了白细胞(wbc)数量。与对照组相比,各组大鼠淋巴细胞计数均显著升高(p)。结论:电喷雾技术制备的EP-Eudragit RS100 NPs可显著增强紫荆提取物的免疫刺激作用。
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引用次数: 0
Current and Novel Emerging Medical Therapies for Peripheral Artery Disease: A Literature Review. 当前和新出现的外周动脉疾病的医学治疗:文献综述。
IF 3.6 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-01 DOI: 10.34172/apb.2023.025
AmirAhmad Arabzadeh, Elnaz Faghfuri, Saiedeh Razi Soofiyani, Elaheh Dalir Abdolahinia, Samaneh Siapush, Kazem Nejati-Koshki, Bita Shahrami, Vahid Asghariazar, Yasamin Pahlavan

Despite the improvements in endovascular techniques during the last decades, there is still an increase in the prevalence of peripheral artery disease (PAD) with limited practical treatment, which timeline impact of any intervention for critical limb ischemia (CLI) is poor. Most common treatments are not suitable for many patients due to their underlying diseases, including aging and diabetes. On the one hand, there are limitations for current therapies due to the contraindications of some individuals, and on the other hand, there are many side effects caused by common medications, for instance, anticoagulants. Therefore, novel treatment strategies like regenerative medicine, cell-based therapies, Nano-therapy, gene therapy, and targeted therapy, besides other traditional drugs combination therapy for PAD, are newly considered promising therapy. Genetic material encoding for specific proteins concludes with a potential future for developed treatments. Novel approaches for therapeutic angiogenesis directly used the angiogenetic factors originating from key biomolecules such as genes, proteins, or cell-based therapy to induce blood vessel formation in adult tissues to initiate the recovery process in the ischemic limb. As PAD is associated with high mortality and morbidity of patients causing disability, considering the limited treatment choices for these patients, developing new treatment strategies to prevent PAD progression and extending life expectancy, and preventing threatening complications is urgently needed. This review aims to introduce the current and the novel strategies for PAD treatment that lead to new challenges for relief the patient's suffered from the disorder.

尽管在过去的几十年里血管内技术得到了改进,但外周动脉疾病(PAD)的患病率仍然在增加,实际治疗方法有限,任何干预对严重肢体缺血(CLI)的时间影响都很差。大多数常见的治疗方法都不适合许多患者,因为他们有潜在的疾病,包括衰老和糖尿病。一方面,由于某些个体的禁忌症,目前的治疗方法存在局限性,另一方面,常见药物如抗凝血剂会产生许多副作用。因此,除了传统的药物联合治疗外,再生医学、细胞疗法、纳米疗法、基因疗法、靶向治疗等新的治疗策略被认为是治疗PAD的新方法。编码特定蛋白质的遗传物质具有开发治疗方法的潜在未来。治疗性血管生成的新方法直接使用源自关键生物分子的血管生成因子,如基因、蛋白质或基于细胞的治疗来诱导成人组织中的血管形成,以启动缺血肢体的恢复过程。由于PAD患者致残的死亡率和发病率较高,考虑到这些患者的治疗选择有限,开发新的治疗策略以防止PAD进展和延长预期寿命,并预防威胁并发症是迫切需要的。本文旨在介绍当前和新的PAD治疗策略,为减轻患者的痛苦带来新的挑战。
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引用次数: 1
Coenzyme Q10 and Its Therapeutic Potencies Against COVID-19 and Other Similar Infections: A Molecular Review. 辅酶Q10及其对COVID-19和其他类似感染的治疗作用:分子综述
IF 3.6 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-01 DOI: 10.34172/apb.2023.026
Mohammad Fakhrolmobasheri, Mahnaz-Sadat Hosseini, Seyedeh-Ghazal Shahrokh, Zahra Mohammadi, Mohammad-Javad Kahlani, Seyed-Erfan Majidi, Mehrdad Zeinalian

Purpose: New lethal coronavirus disease 2019 (COVID-19), currently, has been converted to a disastrous pandemic worldwide. As there has been found no definitive treatment for the infection in this review we focused on molecular aspects of coenzyme Q10 (CoQ10) and possible therapeutic potencies of CoQ10 against COVID-19 and similar infections. Methods: This is a narrative review in which we used some authentic resources including PubMed, ISI, Scopus, Science Direct, Cochrane, and some preprint databases, the molecular aspects of CoQ10 effects, regarding to the COVID-19 pathogenesis, have been analyzed and discussed. Results: CoQ10 is an essential cofactor in the electron transport chain of the phosphorylative oxidation system. It is a powerful lipophilic antioxidant, anti-apoptotic, immunomodulatory and anti-inflammatory supplement which has been tested for the management and prevention of a variety of diseases particularly diseases with inflammatory pathogenesis. CoQ10 is a strong anti-inflammatory agent which can reduce tumor necrosis factor-α (TNF-α), interleukin (IL)- 6, C-reactive protein (CRP), and other inflammatory cytokines. The cardio-protective role of CoQ10 in improving viral myocarditis and drug induced cardiotoxicity has been determined in different studies. CoQ10 could also improve the interference in the RAS system caused by COVID-19 through exerting anti-Angiotensin II effects and decreasing oxidative stress. CoQ10 passes easily through blood-brain barrier (BBB). As a neuroprotective agent CoQ10 can reduce oxidative stress and modulate the immunologic reactions. These properties may help to reduce CNS inflammation and prevent BBB damage and neuronal apoptosis in COVID-19 patients. Conclusion: CoQ10 supplementation may prevent the COVID-19-induced morbidities with a potential protective role against the deleterious consequences of the disease, further clinical evaluations are encouraged.

目的:2019年新型致命冠状病毒病(COVID-19)目前已转变为全球性灾难性大流行。由于目前还没有发现针对这种感染的明确治疗方法,因此在本综述中,我们将重点关注辅酶Q10 (CoQ10)的分子方面以及CoQ10对COVID-19和类似感染的可能治疗作用。方法:利用PubMed、ISI、Scopus、Science Direct、Cochrane及部分预印数据库等权威资源,从分子层面对CoQ10在COVID-19发病机制中的作用进行分析和探讨。结果:辅酶q10是磷酸化氧化系统电子传递链中必不可少的辅助因子。它是一种强大的亲脂性抗氧化,抗凋亡,免疫调节和抗炎补充剂,已被测试用于管理和预防各种疾病,特别是炎症发病的疾病。CoQ10是一种强抗炎剂,可降低肿瘤坏死因子-α (TNF-α)、白细胞介素(IL)- 6、c反应蛋白(CRP)等炎性因子。不同的研究已经确定了辅酶q10在改善病毒性心肌炎和药物性心脏毒性中的心脏保护作用。CoQ10还可以通过发挥抗血管紧张素II作用和降低氧化应激来改善COVID-19对RAS系统的干扰。辅酶q10很容易通过血脑屏障(BBB)。辅酶q10作为一种神经保护剂,可以减轻氧化应激,调节免疫反应。这些特性可能有助于减少COVID-19患者的中枢神经系统炎症,防止血脑屏障损伤和神经元凋亡。结论:补充辅酶q10可预防covid -19引起的疾病,对疾病的有害后果具有潜在的保护作用,鼓励进一步的临床评估。
{"title":"Coenzyme Q10 and Its Therapeutic Potencies Against COVID-19 and Other Similar Infections: A Molecular Review.","authors":"Mohammad Fakhrolmobasheri,&nbsp;Mahnaz-Sadat Hosseini,&nbsp;Seyedeh-Ghazal Shahrokh,&nbsp;Zahra Mohammadi,&nbsp;Mohammad-Javad Kahlani,&nbsp;Seyed-Erfan Majidi,&nbsp;Mehrdad Zeinalian","doi":"10.34172/apb.2023.026","DOIUrl":"https://doi.org/10.34172/apb.2023.026","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> New lethal coronavirus disease 2019 (COVID-19), currently, has been converted to a disastrous pandemic worldwide. As there has been found no definitive treatment for the infection in this review we focused on molecular aspects of coenzyme Q<sub>10</sub> (CoQ<sub>10</sub>) and possible therapeutic potencies of CoQ<sub>10</sub> against COVID-19 and similar infections. <b><i>Methods:</i></b> This is a narrative review in which we used some authentic resources including PubMed, ISI, Scopus, Science Direct, Cochrane, and some preprint databases, the molecular aspects of CoQ<sub>10</sub> effects, regarding to the COVID-19 pathogenesis, have been analyzed and discussed. <b><i>Results:</i></b> CoQ<sub>10</sub> is an essential cofactor in the electron transport chain of the phosphorylative oxidation system. It is a powerful lipophilic antioxidant, anti-apoptotic, immunomodulatory and anti-inflammatory supplement which has been tested for the management and prevention of a variety of diseases particularly diseases with inflammatory pathogenesis. CoQ<sub>10</sub> is a strong anti-inflammatory agent which can reduce tumor necrosis factor-α (TNF-α), interleukin (IL)- 6, C-reactive protein (CRP), and other inflammatory cytokines. The cardio-protective role of CoQ<sub>10</sub> in improving viral myocarditis and drug induced cardiotoxicity has been determined in different studies. CoQ<sub>10</sub> could also improve the interference in the RAS system caused by COVID-19 through exerting anti-Angiotensin II effects and decreasing oxidative stress. CoQ<sub>10</sub> passes easily through blood-brain barrier (BBB). As a neuroprotective agent CoQ<sub>10</sub> can reduce oxidative stress and modulate the immunologic reactions. These properties may help to reduce CNS inflammation and prevent BBB damage and neuronal apoptosis in COVID-19 patients. <b><i>Conclusion:</i></b> CoQ<sub>10</sub> supplementation may prevent the COVID-19-induced morbidities with a potential protective role against the deleterious consequences of the disease, further clinical evaluations are encouraged.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 2","pages":"233-243"},"PeriodicalIF":3.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9764065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Liposome-Fe3 O4-Doxorubicin Mediated Treatment of Melanoma Tumors. 脂质体- fe3o4 -阿霉素介导的黑色素瘤治疗。
IF 3.6 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-01 DOI: 10.34172/apb.2023.034
Azalia Azlegini, Sirus Javadpour, Mohamad Ebrahim Bahrololoom

Purpose: Magnetic hyperthermia is a treatment method based on eddy currents, hysteresis, and relaxation mechanisms of magnetic nanoparticles (MNPs). MNPs such as Fe3 O4 have the ability to generate heat under an alternating magnetic field. Heat sensitive liposomes (Lip) convert from lipid layer to liquid layer through heat generated by MNPs and can release drugs. Methods: In this study, different groups of doxorubicin (DOX), MNPs and liposomes were evaluated. The MNPs were synthesized by co-precipitation method. The MNPs, DOX and a combination of MNPs and DOX were efficiently loaded into the liposomes using the evaporator rotary technique. Magnetic properties, microstructure, specific absorption rate (SAR), zeta potential, loading percentage of the MNPs and DOX concentration in liposomes, in vitro drug release of liposomes were studied. Finally, the necrosis percentage of cancer cells in C57BL/6J mice bearing melanoma tumors was assessed for all groups. Results: The loading percentages of MNPs and concentration of DOX in the liposomes were 18.52 and 65% respectively. The Lip-DOX-MNPs at the buffer citrate solution, showed highly SAR as the solution temperature reached 42°C in 5 minutes. The release of DOX occurred in a pH-dependent manner. The volume of tumor in the therapeutic groups containing the MNPs significantly decreased compared to the others. Numerical analysis showed that the tumor volume in mice receiving Lip-MNPs-DOX was 9.29% that of the control and a histological examination of the tumor section showed 70% necrosis. Conclusion: The Lip-DOX-MNPs could be effective agents which reduce malignant skin tumors growth and increase cancer cell necrosis.

目的:磁热疗是一种基于磁纳米颗粒(MNPs)涡流、磁滞和弛豫机制的治疗方法。像fe3o4这样的MNPs能够在交变磁场下产生热量。热敏脂质体(Lip)通过MNPs产生的热量从脂质层转化为液体层,并释放药物。方法:对不同组的阿霉素(DOX)、MNPs和脂质体进行评价。采用共沉淀法合成MNPs。利用蒸发器旋转技术将MNPs、DOX以及MNPs和DOX的组合有效地装载到脂质体中。研究了脂质体的磁性、微观结构、比吸收率(SAR)、zeta电位、MNPs的负载率和DOX浓度,以及脂质体的体外药物释放情况。最后,评估各组携带黑色素瘤的C57BL/6J小鼠的癌细胞坏死百分比。结果:脂质体中MNPs的负载率为18.52%,DOX的浓度为65%。Lip-DOX-MNPs在缓冲柠檬酸溶液中,当溶液温度在5分钟内达到42°C时,表现出很高的SAR。DOX的释放以ph依赖的方式发生。与其他治疗组相比,含有MNPs的治疗组的肿瘤体积显著减少。数值分析表明,Lip-MNPs-DOX小鼠的肿瘤体积为对照组的9.29%,肿瘤切片组织学检查显示70%坏死。结论:Lip-DOX-MNPs可作为抑制皮肤恶性肿瘤生长、促进肿瘤细胞坏死的有效药物。
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引用次数: 1
The Impact of Single Nucleotide Polymorphisms on the Pharmacokinetics of Tacrolimus in Kidney Allograft Recipients of Northern-West, Iran. 单核苷酸多态性对他克莫司在伊朗西北部肾移植受者体内药代动力学的影响。
IF 3.6 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-01 DOI: 10.34172/apb.2023.038
Elaheh Jabbari Hagh, Ali Mousavi, Seyyedeh Mina Hejazian, Mehdi Haghi, Samaneh Esfahanian, Elham Ahmadian, Sepideh Zununi Vahed, Mohammadreza Ardalan

Purpose: Calcineurin inhibitors (CNIs) such as tacrolimus are a major immunosuppressive therapy after renal transplantation, which inhibit cytokine expression. The pharmacokinetics of such drugs is influenced by cytochrome P450 (CYP) enzymes, multi-drug resistance-1 (MDR-1), and C25385T pregnane X receptor (PXR). This study aimed to investigate the impact of single nucleotide polymorphisms (SNP) in these genes on the ratio of tacrolimus level per drug dosage (C/D ratio), acute graft rejection, and viral infections. Methods: Kidney transplantation recipients (n=65) under similar immunosuppressive treatment were included. Amplification refractory mutation systempolymerase chain reaction (ARMS-PCR) method was applied to amplify the loci containing the SNPs of interest. Results: Overall, 65 patients with a male/female ratio of 37/28 were included. The mean age was 38±1.75 years. The variant allele frequencies of CYP3A5*3, MDR-1 C3435T, and PXR C25385T were 95.38, 20.77, and 26.92%, respectively. No significant correlations were found between the studied SNPs and the tacrolimus C/D ratios. However, there was a significant difference in the C/D ratios at 2 and 8 weeks in homozygote CYP3A5 *3/*3 carriers (P=0.015). No significant association was found between the studied polymorphisms and viral infections and acute graft rejection (P>0.05). Conclusion: Homozygote CYP3A5 *3/*3 genotype could influence the tacrolimus metabolism rate (C/D ratio).

目的:钙调磷酸酶抑制剂(CNIs)如他克莫司是肾移植后主要的免疫抑制药物,可抑制细胞因子的表达。这些药物的药代动力学受细胞色素P450 (CYP)酶、多药耐药-1 (MDR-1)和C25385T妊娠X受体(PXR)的影响。本研究旨在探讨这些基因的单核苷酸多态性(SNP)对他克莫司剂量比(C/D比)、急性移植排斥反应和病毒感染的影响。方法:采用相似免疫抑制治疗的肾移植受者(n=65)。扩增难解突变系统聚合酶链反应(ARMS-PCR)法扩增目标snp位点。结果:共纳入65例患者,男女比例为37/28。平均年龄38±1.75岁。CYP3A5*3、MDR-1 C3435T和PXR C25385T变异等位基因频率分别为95.38%、20.77%和26.92%。snp与他克莫司C/D比值无显著相关性。纯合子CYP3A5 *3/*3携带者在2周和8周时的C/D比有显著差异(P=0.015)。所研究的多态性与病毒感染和急性移植排斥反应无显著相关性(P>0.05)。结论:纯合子CYP3A5 *3/*3基因型影响他克莫司代谢率(C/D比)。
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引用次数: 0
Bioactive PI3-kinase/Akt/mTOR Inhibitors in Targeted Lung Cancer Therapy. 生物活性pi3激酶/Akt/mTOR抑制剂在肺癌靶向治疗中的应用
IF 3.6 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.34172/apb.2023.003
Somayyeh Ghareghomi, Vahideh Atabaki, Naseh Abdollahzadeh, Shahin Ahmadian, Salar Hafez Ghoran

One of the central signaling pathways with a regulatory effect on cell proliferation and survival is Akt/mTOR. In many human cancer types, for instance, lung cancer, the overexpression of Akt/mTOR has been reported. For this reason, either targeting cancer cells by synthetic or natural products affecting the Akt/mTOR pathway down-regulation is a useful strategy in cancer therapy. Direct inhibition of the signaling pathway or modulation of each related molecule could have significant feedback on the growth and proliferation of cancer cells. A variety of secondary metabolites has been identified to directly inhibit the AKT/mTOR signaling, which is important in the field of drug discovery. Naturally occurring nitrogenous and phenolic compounds can emerge as two pivotal classes of natural products possessing anticancer abilities. Herein, we have summarized the alkaloids and flavonoids for lung cancer treatment together with all the possible mechanisms of action relying on the Akt/mTOR pathway down-regulation. This review suggested that in search of new drugs, phytochemicals could be considered as promising scaffolds to be developed into efficient drugs for the treatment of cancer. In this review, the terms "Akt/mTOR", "Alkaloid", "flavonoid", and "lung cancer" were searched without any limitation in search criteria in Scopus, PubMed, Web of Science, and Google scholar engines.

Akt/mTOR是调控细胞增殖和存活的主要信号通路之一。在许多人类癌症类型中,例如肺癌,Akt/mTOR的过度表达已被报道。因此,通过影响Akt/mTOR通路下调的合成或天然产物靶向癌细胞是一种有效的癌症治疗策略。直接抑制信号通路或调节各相关分子对癌细胞的生长和增殖有显著的反馈作用。多种次生代谢物可直接抑制AKT/mTOR信号传导,这在药物研发领域具有重要意义。天然存在的氮化合物和酚类化合物可以作为具有抗癌能力的两类关键天然产物出现。在此,我们总结了生物碱和黄酮类化合物治疗肺癌的作用,以及依赖于Akt/mTOR通路下调的所有可能的作用机制。这一综述表明,在寻找新的药物的过程中,植物化学物质可以被认为是一个有前途的支架,可以开发成有效的治疗癌症的药物。在本文中,我们在Scopus、PubMed、Web of Science和Google学术搜索引擎中对“Akt/mTOR”、“Alkaloid”、“flavonoids”和“lung cancer”等关键词进行了检索,检索条件不受任何限制。
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引用次数: 2
The Potential of Vouacapanes from Pterodon emarginatus Vogel Against COVID-19 Cytokine Storm. 叶面翼龙武棘烷抗COVID-19细胞因子风暴的潜力。
IF 3.6 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.34172/apb.2023.016
Leandra de Almeida Ribeiro Oliveira, Arthur Christian Garcia da Silva, Douglas Vieira Thomaz, Fabiana Brandão, Edemilson Cardoso da Conceição, Marize Campos Valadares, Maria Tereza Freitas Bara, Dâmaris Silveira

Purpose: The emergence of the COVID-19 pandemic has led to the search for potential therapeutic responses for various aspects of this disease. Fruits of Pterodon emarginatus Vogel (Fabaceae), sucupira, have been used in Brazilian traditional medicine because of their anti-inflammatory properties, which have been proven in vivo, in vitro, and in silico. Therefore, the aim of this work is to evaluate P. emarginatus oleoresin and isolated diterpenes by in vitro anti-inflammatory models. Methods: In this study, the mechanisms underlying the anti-inflammatory activity of P. emarginatus oleoresin and vouacapanes 6α,19β-diacetoxy-7β,14β-dihydroxyvouacapan (V1), 6α-acetoxy-7β,14β-dihydroxyvouacapan (V2), and methyl 6α-acetoxy-7β-hydroxyvouacapan-17β-oate (V3) were investigated in HaCaT cells. Results: Oleoresin, V2, and V3 inhibited phospholipase A2 (30.78%, 24.96%, and 77.64%, respectively). Both vouacapanes also inhibited the expression of COX-2 (28.3% and 33.17%, respectively). The production of interleukin 6 (IL-6) was inhibited by oleoresin by 35.47%. However, oleoresin did not interfere with Nrf-2 expression or IL-8 production. Conclusion: The results support the ethnomedicinal use of P. emarginatus oleoresin as an anti-inflammatory herbal medicine, and also highlight P. emarginatus oleoresin and isolated vouacapanes as an attractive therapeutic approach for COVID-19 through the reduction or chronological control of the inflammatory mediators IL-6, cyclooxygenase-2 (COX-2), phospholipase A2, and INF-y (indirectly) during the SARS-CoV-2 infection process.

目的:COVID-19大流行的出现促使人们寻找针对该疾病各个方面的潜在治疗反应。翼龙的果实emarginatus Vogel(豆科),sucupira,已被用于巴西传统医学,因为他们的抗炎特性,已被证明在体内,体外和硅。因此,本研究的目的是通过体外抗炎模型对油麻油树脂和分离的二萜进行评价。方法:本研究在HaCaT细胞中研究了油树油树脂和武卡帕烷6α、19β-二乙酰氧基-7β、14β-二羟武卡帕(V1)、6α-乙酰氧基-7β、14β-二羟武卡帕(V2)和甲基6α-乙酰氧基-7β-羟武卡帕-17β-oate (V3)抗炎作用的机制。结果:油脂树脂、V2、V3对磷脂酶A2的抑制作用分别为30.78%、24.96%、77.64%。对COX-2的表达均有抑制作用(分别为28.3%和33.17%)。油脂树脂对白细胞介素6 (IL-6)的抑制作用为35.47%。然而,油树脂不干扰Nrf-2的表达或IL-8的产生。结论:本研究结果支持了艾油树油树脂作为抗炎中药的民族医学应用,并通过降低或按时间顺序(间接)控制SARS-CoV-2感染过程中的炎症介质IL-6、环氧合酶-2 (COX-2)、磷脂酶A2和nf -y,突出了艾油树油树脂和分离的戊烷类化合物是一种有价值的治疗COVID-19的方法。
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引用次数: 0
Taurine in Septic Critically Ill Patients: Plasma versus Blood. 牛磺酸在脓毒症危重病人中的作用:血浆vs血液。
IF 3.6 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.34172/apb.2023.015
Ata Mahmoodpoor, Afsaneh Farjami, Niloufar Farzan, Hamed Hamishehkar, Parina Asgharian, Sarvin Sanaie, Kamran Shadvar, Farnaz Naeimzadeh, Hadi Hamishehkar

Purpose: Sepsis and systemic inflammatory response syndrome (SIRS) encompass various problems throughout the body, and two of its major problems are the creation of oxidative substances in the body and decrease of the body's antioxidant capacity to deal with the stress and organ damage. Optimal enteral nutrition fortified with antioxidant or immunomodulator amino acid is a hot topic concerning sepsis in the critical care setting. Taurine plays a protective role as an antioxidant in cells that is likely to have a protective role in inflammation and cytotoxicity. Methods: In the present study, 20 septic patients and 20 healthy volunteers were enrolled. The blood and plasma taurine levels of the patients on days 1, 3 and 7 were measured. Blood and plasma taurine level and the correlation between them, organ failure, and severity of the disease were assessed. Results: Taurine concentrations in the plasma of the septic patients were significantly lower than control group, and the whole blood concentrations were significantly higher than those of the control group (P<0.001). There was not a significant correlation between the blood and plasma taurine levels in control and septic patients. In addition, there was not any correlation between the severity of the disease, organ failure, mortality, and plasma as well as the blood concentration of taurine. Conclusion: In septic patients, taurine concentration in plasma and blood are low and high, respectively. These concentrations are not linked to each other and not associated with the patients' outcome, and the disease severity, and organ failure.

目的:脓毒症和全身炎症反应综合征(SIRS)包括全身的各种问题,其中两个主要问题是体内氧化物质的产生和身体抗氧化能力的下降,以应对压力和器官损伤。最佳肠内营养强化抗氧化或免疫调节剂氨基酸是一个热门话题有关败血症在重症监护设置。牛磺酸作为抗氧化剂在细胞中起保护作用,可能在炎症和细胞毒性中起保护作用。方法:选取20例脓毒症患者和20例健康志愿者。测定患者第1、3、7天的血液和血浆牛磺酸水平。评估血液和血浆牛磺酸水平及其与器官衰竭和疾病严重程度的相关性。结果:脓毒症患者血浆中牛磺酸浓度显著低于对照组,全血中牛磺酸浓度显著高于对照组(p结论:脓毒症患者血浆中牛磺酸浓度低,血中牛磺酸浓度高。这些浓度彼此之间没有联系,也与患者的预后、疾病严重程度和器官衰竭无关。
{"title":"Taurine in Septic Critically Ill Patients: Plasma versus Blood.","authors":"Ata Mahmoodpoor,&nbsp;Afsaneh Farjami,&nbsp;Niloufar Farzan,&nbsp;Hamed Hamishehkar,&nbsp;Parina Asgharian,&nbsp;Sarvin Sanaie,&nbsp;Kamran Shadvar,&nbsp;Farnaz Naeimzadeh,&nbsp;Hadi Hamishehkar","doi":"10.34172/apb.2023.015","DOIUrl":"https://doi.org/10.34172/apb.2023.015","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Sepsis and systemic inflammatory response syndrome (SIRS) encompass various problems throughout the body, and two of its major problems are the creation of oxidative substances in the body and decrease of the body's antioxidant capacity to deal with the stress and organ damage. Optimal enteral nutrition fortified with antioxidant or immunomodulator amino acid is a hot topic concerning sepsis in the critical care setting. Taurine plays a protective role as an antioxidant in cells that is likely to have a protective role in inflammation and cytotoxicity. <b><i>Methods:</i></b> In the present study, 20 septic patients and 20 healthy volunteers were enrolled. The blood and plasma taurine levels of the patients on days 1, 3 and 7 were measured. Blood and plasma taurine level and the correlation between them, organ failure, and severity of the disease were assessed. <b><i>Results:</i></b> Taurine concentrations in the plasma of the septic patients were significantly lower than control group, and the whole blood concentrations were significantly higher than those of the control group (<i>P</i><0.001). There was not a significant correlation between the blood and plasma taurine levels in control and septic patients. In addition, there was not any correlation between the severity of the disease, organ failure, mortality, and plasma as well as the blood concentration of taurine. <b><i>Conclusion:</i></b> In septic patients, taurine concentration in plasma and blood are low and high, respectively. These concentrations are not linked to each other and not associated with the patients' outcome, and the disease severity, and organ failure.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 1","pages":"143-149"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10599948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Advanced pharmaceutical bulletin
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