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Integration of Machine Learning and Structural Analysis for Predicting Peptide Antibiofilm Effects: Advancements in Drug Discovery for Biofilm-Related Infections 整合机器学习和结构分析预测肽抗生物膜效应:生物膜相关感染药物发现的进展
4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-09-30 DOI: 10.5812/ijpr-138704
Fatemeh Ebrahimi Tarki, Mahboobeh Zarrabi, Ahya Abdiali, Mahkame Sharbatdar
Background: The rise of antibiotic resistance has become a major concern, signaling the end of the golden age of antibiotics. Bacterial biofilms, which exhibit high resistance to antibiotics, significantly contribute to the emergence of antibiotic resistance. Therefore, there is an urgent need to discover new therapeutic agents with specific characteristics to effectively combat biofilm-related infections. Studies have shown the promising potential of peptides as antimicrobial agents. Objectives: This study aimed to establish a cost-effective and streamlined computational method for predicting the antibiofilm effects of peptides. This method can assist in addressing the intricate challenge of designing peptides with strong antibiofilm properties, a task that can be both challenging and costly. Methods: A positive library, consisting of peptide sequences with antibiofilm activity exceeding 50%, was assembled, along with a negative library containing quorum-sensing peptides. For each peptide sequence, feature vectors were calculated, while considering the primary structure, the order of amino acids, their physicochemical properties, and their distributions. Multiple supervised learning algorithms were used to classify peptides with significant antibiofilm effects for subsequent experimental evaluations. Results: The computational approach exhibited high accuracy in predicting the antibiofilm effects of peptides, with accuracy, precision, Matthew's correlation coefficient (MCC), and F1 score of 99%, 99%, 0.97, and 0.99, respectively. The performance level of this computational approach was comparable to that of previous methods. This study introduced a novel approach by combining the feature space with high antibiofilm activity. Conclusions: In this study, a reliable and cost-effective method was developed for predicting the antibiofilm effects of peptides using a computational approach. This approach allows for the identification of peptide sequences with substantial antibiofilm activities for further experimental investigations. Accessible source codes and raw data of this study can be found online (hiABF), providing easy access and enabling future updates.
背景:抗生素耐药性的上升已经成为一个主要问题,标志着抗生素黄金时代的结束。细菌生物膜对抗生素具有较高的耐药性,是抗生素耐药性产生的重要因素。因此,迫切需要发现具有特异性的新型治疗剂来有效对抗生物膜相关感染。研究表明,多肽作为抗菌药物具有广阔的应用前景。目的:本研究旨在建立一种经济高效的计算方法来预测多肽的抗生物膜作用。这种方法可以帮助解决设计具有强抗菌膜特性的肽的复杂挑战,这是一项既具有挑战性又昂贵的任务。方法:将含有抗菌膜活性超过50%的肽序列的阳性文库与含有群体感应肽的阴性文库进行组装。对于每个肽序列,考虑初级结构、氨基酸顺序、理化性质及其分布,计算特征向量。使用多个监督学习算法对具有显著抗生物膜效应的肽进行分类,以进行后续实验评估。结果:计算方法预测多肽的抗菌膜效应具有较高的准确性,准确度为99%,精密度为99%,马修相关系数(MCC)为0.97,F1评分为0.99。这种计算方法的性能水平与以前的方法相当。本研究提出了一种将特征空间与高抗菌膜活性相结合的新方法。结论:在本研究中,我们开发了一种可靠且经济的方法来预测多肽的抗生物膜效应。这种方法允许鉴定具有大量抗生素膜活性的肽序列,用于进一步的实验研究。可访问的源代码和本研究的原始数据可以在网上(hiABF)找到,提供方便的访问和将来的更新。
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引用次数: 0
Designing and Expression of Recombinant Chimeric Spike Protein from SARS-CoV-2 in Escherichia coli and Its Immunogenicity Assessment 重组SARS-CoV-2嵌合刺突蛋白在大肠杆菌中的设计表达及其免疫原性评价
4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-09-10 DOI: 10.5812/ijpr-137751
Sahar Karimi, Shahram Nazarian, Fattah Sotoodehnejadnematalahi, Roohollah Dorostkar, Jafar Amani
: Since December 2019, the world has been grappling with an ongoing global COVID-19 pandemic. Various virus variants have emerged over the past two years, each posing a greater threat than its predecessors. The recent appearance of the omicron variant (B.1.1.529) has raised significant alarm within the field of epidemiology due to its highly contagious nature and rapid transmission rate. The omicron variant possessed mutations in the key receptor-binding domain (RBD) region, the S region, and these modifications have shown a notable impact on the strain's susceptibility to neutralizing antibodies. Developing safe and efficient vaccines to prevent a future severe acute respiratory outbreak of coronavirus syndrome 2 (SARS-CoV-2) is significant. Viral surface spike proteins are ideal targets for vaccines. This study aimed to find a multi-subunit chimeric vaccine. After conducting bioinformatics analysis, the recombinant spike (RS) protein of SARS-CoV-2 was deliberately designed and subsequently produced using E. coli expression systems. The immunogenicity of RS and neutralizing antibody responses were evaluated on immunized BALB/c mice. There was a significant difference in antibody titers between RS-immunized mice and control groups. The endpoint of the serum antibody titer of mice immunized with our chimeric protein was 2.5 times higher than that of the negative control. The chimeric construct could present multiple antigens simultaneously, influentially affecting immunization. Sera from mice vaccinated by RS could recognize the SARS-CoV-2 virus and neutralize antibodies. Our chimeric peptide could bind to antibodies in the serum of patients infected with different serotypes of the SARS-CoV-2 virus, such as alpha, delta, and omicron variants. The results indicated that the RS protein would be a potential novel antigenic candidate for subunit vaccine development and could be used as a useful alternative to generate diagnostic serological tests for SARS-CoV-2 infection.
自2019年12月以来,世界一直在努力应对持续的全球COVID-19大流行。在过去两年中出现了各种各样的病毒变种,每一种病毒都比前一种病毒构成更大的威胁。最近出现的组粒变异(B.1.1.529)由于其高度传染性和快速传播率,在流行病学领域引起了重大警报。该组粒变体在关键受体结合域(RBD)区域S区发生突变,这些修饰对该菌株对中和抗体的易感性有显著影响。开发安全有效的疫苗以预防未来冠状病毒综合征2 (SARS-CoV-2)的严重急性呼吸道暴发具有重要意义。病毒表面刺突蛋白是疫苗的理想靶点。本研究旨在寻找一种多亚基嵌合疫苗。经过生物信息学分析,我们设计了SARS-CoV-2的重组刺突蛋白(RS),并利用大肠杆菌表达系统进行了生产。在免疫BALB/c小鼠上评价RS的免疫原性和中和抗体反应。rs免疫小鼠的抗体滴度与对照组有显著差异。用我们的嵌合蛋白免疫小鼠的终点血清抗体滴度比阴性对照高2.5倍。嵌合结构可同时呈递多种抗原,影响免疫。经RS疫苗接种的小鼠血清能够识别SARS-CoV-2病毒并中和抗体。我们的嵌合肽可以与感染不同血清型SARS-CoV-2病毒(如α、δ和组粒变体)的患者血清中的抗体结合。结果表明,RS蛋白可能是开发亚单位疫苗的一个潜在的新抗原候选物,并可作为产生SARS-CoV-2感染诊断血清学检测的有用替代方法。
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引用次数: 0
Cerasome Versus Liposome: A Comparative Pharmacokinetic Analysis Following Intravenous Administration into Rats 脂质体与脂质体:大鼠静脉给药后的比较药代动力学分析
4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-09-09 DOI: 10.5812/ijpr-138362
Shima Bahri, Erfan Abdollahizad, Iman Mahlooji, Elham Rezaee, Zahra Abbasian, Simin Dadashzadeh
Background: Cerasomes, due to their external siloxane network, demonstrate markedly higher physicochemical stability and, therefore, easier handling and storage than liposomes. Objectives: The main objective of this study was to compare the pharmacokinetics (PK) of cerasome and liposome following intravenous administration. The PK of PEGylated and non-PEGylated cerasomes was also compared to see whether the presence of a hydrophilic siloxane network on the surface of cerasomes can play the role of polyethylene glycol (PEG) in increasing the blood circulation of these vesicles. Methods: Silver sulfide (Ag2S) quantum dots (Qds)-loaded PEGylated and non-PEGylated cerasomes and PEGylated liposomes were fabricated and thoroughly characterized in terms of particle size, polydispersity index, zeta potential, entrapment efficiency, and in vitro stability. For pharmacokinetic evaluation, the free Qds and the selected formulations were intravenously injected into rats, and blood samples were collected for up to 72 hours. Pharmacokinetic parameters were calculated by the non-compartmental method. Results: Both cerasomal and liposomal carriers significantly improved the PK of Qds. For example, the elimination half-life (t1/2) and the area under the plasma concentration-time curve from time 0 to time infinity (AUC0-∞) for the free Qds were 4.39 h and 8.01 µg/mL*h and for cerasomal and liposomal formulations were 28.82 versus 26.95 h and 73.25 versus 62.02 µg/mL*h, respectively. However, compared to each other, the plasma concentration-time profiles of PEGylated cerasomes and liposomes displayed similar patterns, and the statistical comparison of their pharmacokinetic parameters did not show any significant difference between the two types of carriers. For PEGylated cerasomes, t1/2 and AUC0-∞ values were respectively 1.6 and 3.3 times greater than the classic cerasome, indicating that despite the presence of a hydrophilic siloxane network, the incorporation of PEG is necessary to reduce the clearance of cerasomes. Conclusions: The comparable PK of PEGylated cerasomes and liposomes, along with the higher physicochemical stability of cerasomes, can be considered an important advantage for the clinical application of cerasomes. Additionally, the easy surface functionalizing ability of cerasomes confers a dual advantage over liposomes. The study findings also showed that the presence of a hydrophilic siloxane network on the surface of cerasomes alone is not enough to make them circulate long.
背景:脂质体,由于其外部硅氧烷网络,表现出明显更高的物理化学稳定性,因此,比脂质体更容易处理和储存。目的:本研究的主要目的是比较静脉给药后脂质体和脂质体的药代动力学(PK)。我们还比较了聚乙二醇化和非聚乙二醇化的脂质体的PK,以观察脂质体表面亲水性硅氧烷网络的存在是否可以发挥聚乙二醇(PEG)在增加这些囊泡血液循环中的作用。方法:制备装载聚乙二醇化和非聚乙二醇化酶体和聚乙二醇化脂质体的硫化银(Ag2S)量子点,并对其粒径、多分散性指数、zeta电位、包封效率和体外稳定性进行了全面表征。为了进行药代动力学评价,将游离Qds和所选制剂静脉注射到大鼠体内,并采集血样长达72小时。采用非室室法计算药动学参数。结果:血清体和脂质体携带者均能显著改善Qds的PK。例如,自由量子点的消除半衰期(t1/2)和血浆浓度-时间曲线下面积(AUC0-∞)分别为4.39 h和8.01µg/mL*h,血清体和脂质体制剂的消除半衰期分别为28.82 h和26.95 h, 73.25 h和62.02µg/mL*h。然而,聚乙二醇化脂质体和脂质体的血药浓度-时间谱相互比较表现出相似的模式,其药动学参数的统计比较在两类携带者之间没有明显差异。对于聚乙二醇化的cerasome, t1/2和AUC0-∞值分别是经典cerasome的1.6倍和3.3倍,这表明尽管存在亲水性硅氧烷网络,但为了降低cerasome的清除率,PEG的加入是必要的。结论:聚乙二醇化脂质体与脂质体的PK相当,且脂质体具有较高的理化稳定性,可视为脂质体临床应用的重要优势。此外,脂质体易于表面功能化的能力赋予了脂质体的双重优势。研究结果还表明,仅在脂质体表面存在亲水性硅氧烷网络并不足以使它们长时间循环。
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引用次数: 0
A Mechanistic Study on the Fluidization and Enhancement Effects of Cineole Toward Stratum Corneum Intercellular Lamellar Lipids: A Liquid Crystalline Model Approach 桉叶脑对角质层细胞间层状脂质流化和增强作用的机理研究:液晶模型方法
IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-06-22 DOI: 10.5812/ijpharm-134731
L. Karami, H. Moghimi
Background: The stratum corneum (SC) serves as the primary barrier for permeation in human skin. Penetration enhancers, such as 1,8-cineole, are utilized to enhance the permeation of drugs. Cineole increases the permeation of chemicals through different mechanisms. However, its mechanism, particularly at high concentrations, has not been well-studied and is the subject of the present investigation. Objectives: In continuation of our previous studies, the present investigation aims to elucidate the mechanism of action and concentration dependency of the effects of 1,8-cineole on the structure, diffusional properties, and partitioning behavior of the SC at high concentrations. This will be achieved through lamellar liquid crystalline models and ex-vivo skin studies. Methods: A lamellar liquid crystalline lipid matrix model in the presence (25 - 90%, w/w) and absence of cineole was prepared from SC lipids and characterized by X-ray diffraction, differential scanning calorimetry (DSC), Thermogravimetric Analysis (TGA), and Polarized Light Microscopy (PLM) studies. The release of the model lipophilic drug (diazepam) from cineole and cineole-treated matrices and the permeation of the drug from cineole and cineole-containing matrices (as a vehicle similar to the stratum corneum lipids) through excised rat skin were studied. A drug assay was performed by HPLC. Results: The PLM, DSC, and X-ray studies showed that the model matrix had a lamellar gel-liquid crystalline structure, and cineole fluidized the structure concentration dependently and created other mesomorphic textures, such as myelinic figures. Release experiments showed that diffusion coefficients remained almost constant at high cineole concentrations of 40-90%, suggesting similar fluidization states. Skin permeation studies indicated that the diffusion coefficient (estimated from lag-time) increased concentration-dependently and played a role in permeability coefficient (Kp) increments alongside the increased partitioning of the model drug into the skin. Data suggest that high concentrations of cineole at the skin surface might not provide enough cineole in the skin for full fluidization, despite the similarity of the vehicle to SC lipids and even at high concentrations. Conclusions: The enhancement effect of cineole is concentration-dependent and might reach maximum fluidization at certain concentrations, but this maximum might not be easily achievable when cineole is used in formulations as pure or in a vehicle.
背景:角质层(SC)是人体皮肤渗透的主要屏障。渗透促进剂,如1,8-桉树脑,被用来增强药物的渗透。桉树脑通过不同的机制增加化学物质的渗透。然而,其机制,特别是在高浓度时,尚未得到充分研究,这是本研究的主题。目的:在我们之前研究的基础上,本研究旨在阐明1,8-桉树脑在高浓度下对SC结构、扩散特性和分配行为影响的作用机制和浓度依赖性。这将通过层状液晶模型和离体皮肤研究来实现。方法:以SC脂质为原料制备了桉树脑存在(25 - 90%,w/w)和不存在(w/w)的片层状液晶脂质基质模型,并通过x射线衍射、差示扫描量热法(DSC)、热重分析(TGA)和偏光显微镜(PLM)对其进行了表征。研究了桉树脑和桉叶脑处理基质中模型亲脂性药物(安定)的释放,以及药物从桉叶脑和含桉叶脑基质(作为类似于角质层脂质的载体)通过切除大鼠皮肤的渗透。采用高效液相色谱法进行药物含量测定。结果:PLM、DSC和x射线研究表明,该模型基质具有层状凝胶-液晶结构,桉树脑对该结构的浓度进行了流态化,并产生了其他中形态织构,如髓鞘图形。释放实验表明,在桉树脑浓度为40-90%时,扩散系数基本保持不变,表明流体化状态相似。皮肤渗透研究表明,扩散系数(从滞后时间估计)随浓度的增加而增加,并在渗透系数(Kp)增量中发挥作用,同时增加模型药物进入皮肤的分配。数据表明,皮肤表面高浓度的桉树脑可能无法在皮肤中提供足够的桉树脑来实现完全流化,尽管载体与SC脂质相似,甚至在高浓度下也是如此。结论:桉树脑的增强作用是浓度依赖性的,在一定浓度下可能达到最大流化,但当桉树脑作为纯制剂或在载体中使用时,可能不容易达到最大流化。
{"title":"A Mechanistic Study on the Fluidization and Enhancement Effects of Cineole Toward Stratum Corneum Intercellular Lamellar Lipids: A Liquid Crystalline Model Approach","authors":"L. Karami, H. Moghimi","doi":"10.5812/ijpharm-134731","DOIUrl":"https://doi.org/10.5812/ijpharm-134731","url":null,"abstract":"Background: The stratum corneum (SC) serves as the primary barrier for permeation in human skin. Penetration enhancers, such as 1,8-cineole, are utilized to enhance the permeation of drugs. Cineole increases the permeation of chemicals through different mechanisms. However, its mechanism, particularly at high concentrations, has not been well-studied and is the subject of the present investigation. Objectives: In continuation of our previous studies, the present investigation aims to elucidate the mechanism of action and concentration dependency of the effects of 1,8-cineole on the structure, diffusional properties, and partitioning behavior of the SC at high concentrations. This will be achieved through lamellar liquid crystalline models and ex-vivo skin studies. Methods: A lamellar liquid crystalline lipid matrix model in the presence (25 - 90%, w/w) and absence of cineole was prepared from SC lipids and characterized by X-ray diffraction, differential scanning calorimetry (DSC), Thermogravimetric Analysis (TGA), and Polarized Light Microscopy (PLM) studies. The release of the model lipophilic drug (diazepam) from cineole and cineole-treated matrices and the permeation of the drug from cineole and cineole-containing matrices (as a vehicle similar to the stratum corneum lipids) through excised rat skin were studied. A drug assay was performed by HPLC. Results: The PLM, DSC, and X-ray studies showed that the model matrix had a lamellar gel-liquid crystalline structure, and cineole fluidized the structure concentration dependently and created other mesomorphic textures, such as myelinic figures. Release experiments showed that diffusion coefficients remained almost constant at high cineole concentrations of 40-90%, suggesting similar fluidization states. Skin permeation studies indicated that the diffusion coefficient (estimated from lag-time) increased concentration-dependently and played a role in permeability coefficient (Kp) increments alongside the increased partitioning of the model drug into the skin. Data suggest that high concentrations of cineole at the skin surface might not provide enough cineole in the skin for full fluidization, despite the similarity of the vehicle to SC lipids and even at high concentrations. Conclusions: The enhancement effect of cineole is concentration-dependent and might reach maximum fluidization at certain concentrations, but this maximum might not be easily achievable when cineole is used in formulations as pure or in a vehicle.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"1 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2023-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89788613","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}
引用次数: 0
A Mechanistic Study on the Fluidization and Enhancement Effects of Cineole Toward Stratum Corneum Intercellular Lamellar Lipids: A Liquid Crystalline Model Approach 桉叶脑对角质层细胞间层状脂质流化和增强作用的机理研究:液晶模型方法
4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-06-22 DOI: 10.5812/ijpr-134731
Leila Karami, Hamid Reza Moghimi
Background: The stratum corneum (SC) serves as the primary barrier for permeation in human skin. Penetration enhancers, such as 1,8-cineole, are utilized to enhance the permeation of drugs. Cineole increases the permeation of chemicals through different mechanisms. However, its mechanism, particularly at high concentrations, has not been well-studied and is the subject of the present investigation. Objectives: In continuation of our previous studies, the present investigation aims to elucidate the mechanism of action and concentration dependency of the effects of 1,8-cineole on the structure, diffusional properties, and partitioning behavior of the SC at high concentrations. This will be achieved through lamellar liquid crystalline models and ex-vivo skin studies. Methods: A lamellar liquid crystalline lipid matrix model in the presence (25 - 90%, w/w) and absence of cineole was prepared from SC lipids and characterized by X-ray diffraction, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and polarized light microscopy (PLM) studies. Release of the model lipophilic drug (diazepam) from cineole and cineole-treated matrices and the permeation of the drug from cineole and cineole-containing matrices (as a vehicle similar to the stratum corneum lipids) through excised rat skin were studied. Drug assay was performed by HPLC. Results: The PLM, DSC, and X-ray studies showed that the model matrix had a lamellar gel-liquid crystalline structure, and cineole fluidized the structure concentration-dependently and created other mesomorphic textures, such as myelinic figures. Release experiments showed that diffusion coefficients remained almost constant at high cineole concentrations of 40-90%, suggesting similar fluidization states. Skin permeation studies indicated that the diffusion coefficient (estimated from lag-time) increased concentration-dependently and played a role in permeability coefficient (Kp) increments alongside the increased partitioning of the model drug into the skin. Data suggest that high concentrations of cineole at the skin surface might not provide enough cineole in the skin for full fluidization, despite the similarity of the vehicle to SC lipids and even at high concentrations. Conclusions: The enhancement effect of cineole is concentration-dependent and might reach maximum fluidization at certain concentrations, but this maximum might not be easily achievable when cineole is used in formulations as pure or in a vehicle.
背景:角质层(SC)是人体皮肤渗透的主要屏障。渗透促进剂,如1,8-桉树脑,被用来增强药物的渗透。桉树脑通过不同的机制增加化学物质的渗透。然而,其机制,特别是在高浓度时,尚未得到充分研究,这是本研究的主题。目的:在我们之前研究的基础上,本研究旨在阐明1,8-桉树脑在高浓度下对SC结构、扩散特性和分配行为影响的作用机制和浓度依赖性。这将通过层状液晶模型和离体皮肤研究来实现。方法:以SC脂质为原料制备了桉树脑存在(25 - 90%,w/w)和不存在(25 - 90%,w/w)的片层状液晶脂质基质模型,并通过x射线衍射、差示扫描量热法(DSC)、热重分析(TGA)和偏光显微镜(PLM)对其进行了表征。研究了模型亲脂性药物(安定)从桉叶脑和桉叶脑处理的基质中释放,以及药物从桉叶脑和含桉叶脑的基质(作为类似于角质层脂质的载体)通过切除的大鼠皮肤的渗透。HPLC法测定药物含量。结果:PLM、DSC和x射线研究表明,该模型基质具有层状凝胶-液晶结构,桉树脑对该结构进行了浓度依赖性流化,并产生了其他中形态织构,如髓鞘图形。释放实验表明,在桉树脑浓度为40-90%时,扩散系数基本保持不变,表明流体化状态相似。皮肤渗透研究表明,扩散系数(从滞后时间估计)随浓度的增加而增加,并在渗透系数(Kp)增量中发挥作用,同时增加模型药物进入皮肤的分配。数据表明,皮肤表面高浓度的桉树脑可能无法在皮肤中提供足够的桉树脑来实现完全流化,尽管载体与SC脂质相似,甚至在高浓度下也是如此。结论:桉树脑的增强作用是浓度依赖性的,在一定浓度下可能达到最大流化,但当桉树脑作为纯制剂或在载体中使用时,可能不容易达到最大流化。
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引用次数: 0
Effects of Komouni Formulation (Herbal Product of Persian Medicine) With a Low-Calorie Diet on Cardiometabolic Risk Factors in Overweight and Obese Women: A Triple-Blinded Randomized Clinical Trial 低热量饮食对超重和肥胖女性心脏代谢危险因素的影响:一项三盲随机临床试验
4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-06-21 DOI: 10.5812/ijpr-136114
Zahra Aghabeiglooei, Nazli Namazi, Mehrdad Karimi, Samaneh Soleymani, Mohammad Hossein Ayati, Hossein Rezaeizadeh
Background: The prevalence of obesity has almost tripled since 1975, and obesity places a heavy economic burden on healthcare systems. There is a high tendency to use a variety of complementary medicine modalities for weight management among obese patients. Persian Medicine is an ancient medical school practiced for thousands of years in Iran. Found in reliable Iranian traditional resources, Komouni formulation (KF) is a compound medicine that can be effective in the treatment of obesity. It comprises black caraway (Bunium persicum Boiss.), anise (Pimpinella anisum L.), fennel (Foeniculum vulgare Miller), and ajwain (Trachyspemum ammi L.) Objectives: This study aimed to determine the effects of KF on anthropometric indices and metabolic parameters in overweight and obese women. Methods: This triple-blinded randomized controlled clinical trial was performed on 70 overweight or obese women aged 20 - 40 years, with a body mass index (BMI) of 25 - 34.9 kg/m2. The subjects were randomly divided into two groups (each group n = 35) to receive a calorie-restricted diet with 2 g/day (500 mg 30 minutes before breakfast, 1000 mg 30 minutes before lunch, and 500 mg 30 minutes before dinner) KF or placebo for 8 weeks. Anthropometric indices, food intake, and biochemical parameters were measured at baseline and after the intervention. Results: A total of 60 women (intervention = 30; placebo = 30) completed the trial. After the intervention, the KF group experienced a significant reduction in weight (-4.8 vs. -3.2 kg; P = 0.0001), BMI (-1.8 vs. -0.79 kg/m2; P = 0.0001), waist circumference (-5.28 vs. -3.20 cm; P = 0.004), hip circumference (-0.018 vs. -0.008 cm; P = 0.047), fasting blood sugar (-5.6 vs. 0.33; P = 0.025), and low-density lipoprotein (-11.7 vs. 6.7; P = 0.0001), compared to the placebo group. None of the patients in the intervention and placebo groups reported any side effects. Conclusions: Using KF, along with a calorie-restricted diet, can reduce cardiometabolic risk factors in overweight and obese women. However, further studies are needed to elucidate the efficacy of KF as a complementary therapy in obesity.
背景:自1975年以来,肥胖的患病率几乎增加了两倍,肥胖给医疗保健系统带来了沉重的经济负担。在肥胖患者中,使用各种补充医学模式进行体重管理的趋势很高。波斯医学是一种古老的医学流派,在伊朗已有数千年的历史。在可靠的伊朗传统资源中发现,Komouni配方(KF)是一种可以有效治疗肥胖的复合药物。它包括黑香菜(Bunium persicum Boiss.)、茴香(Pimpinella anisum L.)、茴香(Foeniculum vulgare Miller)和茴香(Trachyspemum ammi L.)。目的:本研究旨在确定KF对超重和肥胖女性人体测量指标和代谢参数的影响。方法:对70名体重指数(BMI)在25 ~ 34.9 kg/m2之间、年龄在20 ~ 40岁的超重或肥胖女性进行三盲随机对照临床试验。受试者被随机分为两组(每组n = 35),接受热量限制饮食,每天2克(早餐前30分钟500毫克,午餐前30分钟1000毫克,晚餐前30分钟500毫克)KF或安慰剂,为期8周。在基线和干预后测量人体测量指数、食物摄入量和生化参数。结果:共60名妇女(干预= 30;安慰剂= 30)完成试验。干预后,KF组体重显著减轻(-4.8 vs -3.2 kg;P = 0.0001), BMI (-1.8 vs. -0.79 kg/m2;P = 0.0001),腰围(-5.28 vs -3.20 cm;P = 0.004)、臀围(-0.018 vs. -0.008 cm;P = 0.047),空腹血糖(-5.6 vs. 0.33;P = 0.025),低密度脂蛋白(-11.7 vs. 6.7;P = 0.0001),与安慰剂组相比。在干预组和安慰剂组中,没有患者报告有任何副作用。结论:使用KF和限制卡路里的饮食可以减少超重和肥胖妇女的心脏代谢危险因素。然而,需要进一步的研究来阐明KF作为肥胖补充疗法的功效。
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引用次数: 0
Effects of Komouni Formulation (Herbal Product of Persian Medicine) With a Low-Calorie Diet on Cardiometabolic Risk Factors in Overweight and Obese Women: A Triple-Blinded Randomized Clinical Trial 低热量饮食对超重和肥胖女性心脏代谢危险因素的影响:一项三盲随机临床试验
IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-06-21 DOI: 10.5812/ijpharm-136114
Zahra Aghabeiglooei, N. Namazi, M. Karimi, S. Soleymani, M. Ayati, H. Rezaeizadeh
Background: The prevalence of obesity has almost tripled since 1975, and obesity places a heavy economic burden on healthcare systems. There is a high tendency to use a variety of complementary medicine modalities for weight management among obese patients. Persian Medicine is an ancient medical school practiced for thousands of years in Iran. Found in reliable Iranian traditional resources, Komouni formulation (KF) is a compound medicine that can be effective in the treatment of obesity. It comprises black caraway (Bunium persicum Boiss.), anise (Pimpinella anisum L.), fennel (Foeniculum vulgare Miller), and ajwain (Trachyspemum ammi L.) Objectives: This study aimed to determine the effects of KF on anthropometric indices and metabolic parameters in overweight and obese women. Methods: This triple-blinded randomized controlled clinical trial was performed on 70 overweight or obese women aged 20 - 40 years, with a body mass index (BMI) of 25 - 34.9 kg/m2. The subjects were randomly divided into two groups (each group n = 35) to receive a calorie-restricted diet with 2 g/day (500 mg 30 minutes before breakfast, 1000 mg 30 minutes before lunch, and 500 mg 30 minutes before dinner) KF or placebo for 8 weeks. Anthropometric indices, food intake, and biochemical parameters were measured at baseline and after the intervention. Results: A total of 60 women (intervention = 30; placebo = 30) completed the trial. After the intervention, the KF group experienced a significant reduction in weight (-4.8 vs. -3.2 kg; P = 0.0001), BMI (-1.8 vs. -0.79 kg/m2; P = 0.0001), waist circumference (-5.28 vs. -3.20 cm; P = 0.004), hip circumference (-0.018 vs. -0.008 cm; P = 0.047), fasting blood sugar (-5.6 vs. 0.33; P = 0.025), and low-density lipoprotein (-11.7 vs. 6.7; P = 0.0001), compared to the placebo group. None of the patients in the intervention and placebo groups reported any side effects. Conclusions: Using KF, along with a calorie-restricted diet, can reduce cardiometabolic risk factors in overweight and obese women. However, further studies are needed to elucidate the efficacy of KF as a complementary therapy in obesity.
背景:自1975年以来,肥胖的患病率几乎增加了两倍,肥胖给医疗保健系统带来了沉重的经济负担。在肥胖患者中,使用各种补充医学模式进行体重管理的趋势很高。波斯医学是一种古老的医学流派,在伊朗已有数千年的历史。在可靠的伊朗传统资源中发现,Komouni配方(KF)是一种可以有效治疗肥胖的复合药物。它包括黑香菜(Bunium persicum Boiss.)、茴香(Pimpinella anisum L.)、茴香(Foeniculum vulgare Miller)和茴香(Trachyspemum ammi L.)。目的:本研究旨在确定KF对超重和肥胖女性人体测量指标和代谢参数的影响。方法:对70名体重指数(BMI)在25 ~ 34.9 kg/m2之间、年龄在20 ~ 40岁的超重或肥胖女性进行三盲随机对照临床试验。受试者被随机分为两组(每组n = 35),接受热量限制饮食,每天2克(早餐前30分钟500毫克,午餐前30分钟1000毫克,晚餐前30分钟500毫克)KF或安慰剂,为期8周。在基线和干预后测量人体测量指数、食物摄入量和生化参数。结果:共60名妇女(干预= 30;安慰剂= 30)完成试验。干预后,KF组体重显著减轻(-4.8 vs -3.2 kg;P = 0.0001), BMI (-1.8 vs. -0.79 kg/m2;P = 0.0001),腰围(-5.28 vs -3.20 cm;P = 0.004)、臀围(-0.018 vs. -0.008 cm;P = 0.047),空腹血糖(-5.6 vs. 0.33;P = 0.025),低密度脂蛋白(-11.7 vs. 6.7;P = 0.0001),与安慰剂组相比。在干预组和安慰剂组中,没有患者报告有任何副作用。结论:使用KF和限制卡路里的饮食可以减少超重和肥胖妇女的心脏代谢危险因素。然而,需要进一步的研究来阐明KF作为肥胖补充疗法的功效。
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引用次数: 0
Investigating the Relationship Between the Market Orientation Approach of Pharmaceutical Companies and Their Innovative Performance: The Mediating Role of Dynamic Capabilities and Corporate Social Responsibility 医药企业市场导向方式与创新绩效的关系研究:动态能力和企业社会责任的中介作用
IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-06-19 DOI: 10.5812/ijpr-135094
J. Shirmohammadi, S. Azizi, H. Rasekh, F. Peiravian, Mahyar Polroudi Moghaddam
Background: Given the intensifying competition, adapting to the market environment and meeting customer demands are crucial aspects of the evolving marketing process. Market orientation (MO) represents an organizational culture encompassing shared beliefs and values that prioritize the customer's role in business planning. Objectives: This study seeks to explore the impact of MO on innovative performance (IP) and the potential mediating role of dynamic capabilities (DC) and corporate social responsibility (CSR) in this relationship. Methods: For this study, a structured quantitative questionnaire was distributed to 100 local pharmaceutical companies, resulting in 300 completed questionnaires. Each questionnaire consisted of four main components, which were filled out by three managers from each company: Chief executive officer (CEO), marketing manager, and research and development manager. The collected data were analyzed using SPSS software and structural equation methods to examine the research questions and hypotheses. Results: According to the study findings, there was a positive correlation between employee age, organizational structure, sales volume, and the presence of private companies with IP. MO, DC, and CSR showed a direct and significant relationship with IP. Moreover, the CSR of the company influenced IP through the mediating role of DC. Market orientation was found to enhance explorative IP, leading to improvements in existing processes and services. Conclusions: Based on the study results, it was found that MO has a direct positive impact on IP, leading to improvements in the company's existing processes through its influence on exploratory performance.
背景:随着竞争的加剧,适应市场环境和满足客户需求是不断发展的营销过程的关键方面。市场导向(MO)代表了一种组织文化,包括共同的信念和价值观,优先考虑客户在商业计划中的作用。目的:本研究旨在探讨MO对创新绩效(IP)的影响,以及动态能力(DC)和企业社会责任(CSR)在这一关系中的潜在中介作用。方法:本研究采用结构化定量问卷对100家地方制药企业进行问卷调查,共收集问卷300份。每份问卷由四个主要部分组成,由每家公司的三名经理填写:首席执行官(CEO)、营销经理和研发经理。采用SPSS软件和结构方程法对收集到的数据进行分析,检验研究问题和假设。结果:研究发现,员工年龄、组织结构、销售额与拥有知识产权的民营企业存在正相关。MO、DC和CSR与IP存在直接且显著的关系。企业社会责任通过DC的中介作用影响知识产权。研究发现,以市场为导向可以增强探索性知识产权,从而改善现有流程和服务。结论:根据研究结果,MO对IP有直接的正向影响,通过对探索性绩效的影响,导致公司现有流程的改进。
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引用次数: 0
The Interaction of SRL-2 Peptide with LRP-1 Receptor and Identification of Breast Cancer Related Biomarkers: An In-silico Approach SRL-2肽与LRP-1受体的相互作用及乳腺癌相关生物标志物的鉴定:一种计算机方法
4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-06-11 DOI: 10.5812/ijpr-136624
Yasamin Davatgaran-Taghipour, Yousof Saeedi-Honar, Roya Salehi, Amir Zarebkohan, Vladimir P.Torchilin
Background: Breast cancer is a multifaceted disease characterized by genetic and epigenetic changes that lead to uncontrolled cell growth and metastasis. Early detection and treatment are crucial for managing diseases. Objectives: The objective of this study is to investigate the potential of chimeric peptides for drug delivery and to identify biomarkers associated with breast cancer. Recent studies have shown that the low-density lipoprotein receptor-related protein 1 (LRP-1) receptor has a significant impact on the development of breast cancer. In order to facilitate the identification of biomarkers, we have created a chimeric peptide that has been proven to bind successfully to the LRP-1 receptor. Methods: To identify biomarkers, we utilized advanced computational methods to conduct a meta-analysis of microarray data. Specifically, the g:Profiler and eXpression2Kinases (X2K) databases were utilized to identify gene ontologies and transcription factors. We then used the Human Protein Atlas to identify and assess crucial gene expressions. Results: Our results demonstrated that nucleolar and spindle-associated protein 1 (NUSAP1), melatonin receptor 1A (MELT), and cyclin-dependent kinase 1 (CDK1) are three hub genes that play pivotal roles in the pathogenesis of breast cancer. Conclusions: The research findings provide a deeper understanding of the molecular mechanisms involved in developing breast cancer. These findings have significant implications for developing novel therapies and diagnostics for this disease.
背景:乳腺癌是一种多面性疾病,其特征是遗传和表观遗传改变,导致细胞生长和转移失控。早期发现和治疗对于控制疾病至关重要。目的:本研究的目的是研究嵌合肽用于药物传递的潜力,并确定与乳腺癌相关的生物标志物。近年来的研究表明,低密度脂蛋白受体相关蛋白1 (LRP-1)受体在乳腺癌的发生发展中具有重要影响。为了方便生物标志物的鉴定,我们已经创建了一个嵌合肽,已被证明可以成功地与LRP-1受体结合。方法:为了识别生物标志物,我们利用先进的计算方法对微阵列数据进行了荟萃分析。具体来说,利用g:Profiler和expression2激酶(X2K)数据库来识别基因本体和转录因子。然后,我们使用人类蛋白质图谱来识别和评估关键基因的表达。结果:我们的研究结果表明,核仁和纺锤体相关蛋白1 (NUSAP1)、褪黑素受体1A (MELT)和细胞周期蛋白依赖性激酶1 (CDK1)是三个在乳腺癌发病机制中起关键作用的枢纽基因。结论:本研究结果对乳腺癌发生的分子机制有了更深入的了解。这些发现对开发新的治疗方法和诊断方法具有重要意义。
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引用次数: 0
The Interaction of SRL-2 Peptide with LRP-1 Receptor and Identification of Breast Cancer Related Biomarkers: An In-silico Approach SRL-2肽与LRP-1受体的相互作用及乳腺癌相关生物标志物的鉴定:一种计算机方法
IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-06-11 DOI: 10.5812/ijpharm-136624
Yasamin Davatgaran-Taghipour, Yousef Saeedi-Honar, R. Salehi, A. Zarebkohan, Vladimir P.Torchilin
Background: Breast cancer is a multifaceted disease characterized by genetic and epigenetic changes that lead to uncontrolled cell growth and metastasis. Early detection and treatment are crucial for managing diseases. Objectives: The objective of this study is to investigate the potential of chimeric peptides for drug delivery and to identify biomarkers associated with breast cancer. Recent studies have shown that the low-density lipoprotein receptor-related protein 1 (LRP-1) receptor has a significant impact on the development of breast cancer. In order to facilitate the identification of biomarkers, we have created a chimeric peptide that has been proven to bind successfully to the LRP-1 receptor. Methods: To identify biomarkers, we utilized advanced computational methods to conduct a meta-analysis of microarray data. Specifically, the g:Profiler and eXpression2Kinases (X2K) databases were utilized to identify gene ontologies and transcription factors. We then used the Human Protein Atlas to identify and assess crucial gene expressions. Results: Our results demonstrated that nucleolar and spindle-associated protein 1 (NUSAP1), melatonin receptor 1A (MELT), and cyclin-dependent kinase 1 (CDK1) are three hub genes that play pivotal roles in the pathogenesis of breast cancer. Conclusions: The research findings provide a deeper understanding of the molecular mechanisms involved in developing breast cancer. These findings have significant implications for developing novel therapies and diagnostics for this disease.
背景:乳腺癌是一种多面性疾病,其特征是遗传和表观遗传改变,导致细胞生长和转移失控。早期发现和治疗对于控制疾病至关重要。目的:本研究的目的是研究嵌合肽用于药物传递的潜力,并确定与乳腺癌相关的生物标志物。近年来的研究表明,低密度脂蛋白受体相关蛋白1 (LRP-1)受体在乳腺癌的发生发展中具有重要影响。为了方便生物标志物的鉴定,我们已经创建了一个嵌合肽,已被证明可以成功地与LRP-1受体结合。方法:为了识别生物标志物,我们利用先进的计算方法对微阵列数据进行了荟萃分析。具体来说,利用g:Profiler和expression2激酶(X2K)数据库来识别基因本体和转录因子。然后,我们使用人类蛋白质图谱来识别和评估关键基因的表达。结果:我们的研究结果表明,核仁和纺锤体相关蛋白1 (NUSAP1)、褪黑素受体1A (MELT)和细胞周期蛋白依赖性激酶1 (CDK1)是三个在乳腺癌发病机制中起关键作用的枢纽基因。结论:本研究结果对乳腺癌发生的分子机制有了更深入的了解。这些发现对开发新的治疗方法和诊断方法具有重要意义。
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引用次数: 0
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Iranian Journal of Pharmaceutical Research
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