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Exploring the Interplay between the Warburg Effect and Glucolipotoxicity in Cancer Development: A Novel Perspective on Cancer Etiology. 探索癌症发展过程中沃伯格效应与糖脂毒性之间的相互作用:癌症病因学的新视角
IF 3.1 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-01 Epub Date: 2024-06-22 DOI: 10.34172/apb.2024.049
Maher Monir Akl, Amr Ahmed

The Warburg effect, first observed by Otto Warburg in the 1920s, delineates a metabolic phenomenon in which cancer cells exhibit heightened glucose uptake and lactate production, even under normoxic conditions. This metabolic shift towards glycolysis, despite the presence of oxygen, fuels the energy demands of rapidly proliferating cancer cells. Dysregulated glucose metabolism, characterized by the overexpression of glucose transporters and the redirection of metabolic pathways towards glycolysis, lies at the crux of this metabolic reprogramming. Consequently, the accumulation of lactate as a byproduct contributes to the creation of an acidic tumor microenvironment, fostering tumor progression and metastasis. However, recent research, notably proposed by Maher Akl, introduces a novel perspective regarding the role of glycolipids in cancer metabolism. Akl's glucolipotoxicity hypothesis posits that aberrant glycolipid metabolism, specifically the intracellular buildup of glycolipids, significantly influences tumor initiation and progression. This hypothesis underscores the disruptive impact of accumulated glycolipids on cellular homeostasis, thereby activating oncogenic pathways and promoting carcinogenesis. This perspective aims to synthesize the intricate mechanisms underlying both the Warburg effect and glucolipotoxicity, elucidating their collective contributions to tumor growth and malignancy. By comprehensively understanding these metabolic aberrations, novel avenues for therapeutic intervention targeting the fundamental drivers of cancer initiation and progression emerge, holding promise for more efficacious treatment strategies in the future.

沃伯格效应是奥托-沃伯格在 20 世纪 20 年代首次观察到的,它描述了一种新陈代谢现象,即即使在常氧条件下,癌细胞也会表现出更高的葡萄糖摄取量和乳酸生成量。尽管存在氧气,这种向糖酵解的代谢转变仍能满足快速增殖的癌细胞的能量需求。以葡萄糖转运体过度表达和代谢途径转向糖酵解为特征的葡萄糖代谢失调是这种代谢重编程的关键所在。因此,作为副产品的乳酸盐的积累有助于形成酸性的肿瘤微环境,促进肿瘤的进展和转移。不过,最近的研究,特别是马希尔-阿克勒(Maher Akl)提出的研究,为糖脂在癌症代谢中的作用引入了一个新的视角。Akl 的糖脂毒性假说认为,糖脂代谢异常,特别是糖脂在细胞内的堆积,对肿瘤的发生和发展有重大影响。这一假说强调了积累的糖脂对细胞稳态的破坏性影响,从而激活致癌途径并促进癌变。这一观点旨在综合沃伯格效应和糖脂毒性的复杂机制,阐明它们对肿瘤生长和恶性肿瘤的共同作用。通过全面了解这些代谢畸变,我们将发现针对癌症发生和发展的基本驱动因素进行治疗干预的新途径,为未来制定更有效的治疗策略带来希望。
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引用次数: 0
Nanomedicine Strategies Utilizing Lipid-Based Nanoparticles for Liver Cancer Therapy: Exploring Signaling Pathways and Therapeutic Modalities. 利用脂质纳米粒子治疗肝癌的纳米医学策略:探索信号通路和治疗模式。
IF 3.1 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-01 Epub Date: 2024-07-31 DOI: 10.34172/apb.2024.061
Fereshteh Asgharzadeh, Maryam Moradi Binabaj, Sahar Fanoudi, William C Cho, Yu-Jeong Yang, Maryam Azarian, Mehdi Shafiee Ardestani, Nasim Nasiri, Marzieh Ramezani Farani, Yun Suk Huh

Liver cancer, specifically hepatocellular carcinoma (HCC), is the second leading cause of cancer-related deaths, following pancreatic cancer. The 5-year overall survival rate for HCC remains relatively low. Currently, there are multiple treatment options available for HCC, including systemic drugs, minimally invasive local therapies such as radiofrequency ablation, transarterial chemoembolization (TACE), and arterial radioembolization (TARE), as well as surgical interventions like liver resection or transplantation. However, the effectiveness of drug delivery to the cancerous liver is hindered by pathophysiological changes in the organ. In order to address this challenge, lipid-based nanoparticles (LNPs) have emerged as promising platforms for delivering a diverse range of therapeutic drugs. LNPs offer various structural configurations that enhance their physical stability and enable them to accommodate different types of cargo with varying mechanical properties and degrees of hydrophobicity. In this article, we provide a comprehensive review of the current applications of LNPs in the development of anti-HCC therapies. By examining the existing research, we aim to shed light on the potential future directions and advancements in this field.

肝癌,特别是肝细胞癌(HCC),是继胰腺癌之后导致癌症相关死亡的第二大原因。HCC 的 5 年总生存率仍然相对较低。目前,HCC 有多种治疗方法可供选择,包括全身用药、局部微创疗法(如射频消融、经动脉化疗栓塞(TACE)和动脉放射栓塞(TARE)),以及外科干预(如肝切除或移植)。然而,由于癌变肝脏的病理生理变化,向该器官给药的有效性受到了阻碍。为了应对这一挑战,脂基纳米颗粒(LNPs)已成为一种很有前景的平台,可用于递送各种治疗药物。LNPs 具有各种结构配置,可增强其物理稳定性,使其能够容纳具有不同机械性能和疏水性的不同类型的货物。在本文中,我们全面综述了目前 LNPs 在开发抗肝癌疗法中的应用。通过审查现有研究,我们旨在阐明这一领域未来的潜在方向和进展。
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引用次数: 0
Investigating Functional and Folding Stability of an Engineered E. coli L-asparaginase Harboring Y176F/S241C Mutations. 研究携带 Y176F/S241C 突变的大肠杆菌 L-天冬酰胺酶的功能和折叠稳定性。
IF 3.1 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-01 Epub Date: 2024-06-22 DOI: 10.34172/apb.2024.048
Mahrokh Dastmalchi, Maryam Hamzeh-Mivehroud, Hassan Rezazadeh, Mohammad M Farajollahi, Siavoush Dastmalchi

Purpose: L-asparaginase has been widely recognized as a critical component in the treatment of various types of lymphoproliferative disorders, since its introduction in 1960s. However, its use in some cases leads to allergic reactions rendering the continuation of treatment unfeasible. Thus, the development of L-asparaginase from alternative sources or the production of engineered enzymes have always been considered. This study aimed to produce and evaluate a novel enzyme designed based on the sequence of L-asparaginase from Escherichia coli bacteria with Y176F/S241C mutations.

Methods: The Y176F/S241C mutant L-asparaginase was successfully expressed as the GST-fusion protein in E. coli, and then was subjected to affinity and size exclusion chromatography. The activity of the purified enzyme was determined based on the released ammonia as the result of substrate hydrolysis using Nessler's reagent. Chemical denaturation experiment in the presence of increasing concentration of guanidinium chloride was applied to determine the folding stability of the purified enzyme.

Results: The mutant enzyme was purified with an efficiency of 77-fold but at a low recovery of 0.7%. The determined kinetic parameters Km, Vmax, kcat, specific activity and catalytic efficiency were 13.96 (mM), 2.218 (mM/min), 273.9 (min-1), 237.8 (IU/mg) and 19.62 (mM-1 min-1), respectively. Moreover, unfolding free energy determined by guanidinium chloride induced denaturation for mutated and commercial L-asparaginase enzymes were 8421 J/mol and 5274 J/mol, respectively.

Conclusion: The mutant enzyme showed improved stability over the wild-type. Although the expression level and recovery were low, the mutant L-asparaginase demonstrated promising activity and stability, with potential clinical and industrial applications.

目的:L-天冬酰胺酶自 20 世纪 60 年代问世以来,已被广泛认为是治疗各类淋巴组织增生性疾病的关键成分。然而,在某些病例中使用 L-天冬酰胺酶会导致过敏反应,从而无法继续治疗。因此,人们一直在考虑从其他来源开发 L-天冬酰胺酶或生产工程酶。本研究旨在生产和评估一种新型酶,该酶是根据大肠杆菌的 L-天冬酰胺酶序列设计的,具有 Y176F/S241C 突变:方法:将Y176F/S241C突变的L-天冬酰胺酶在大肠杆菌中成功表达为GST融合蛋白,并进行亲和层析和尺寸排阻层析。纯化后的酶的活性是根据使用奈斯勒试剂水解底物所释放的氨来测定的。在氯化胍浓度增加的情况下进行化学变性实验,以确定纯化酶的折叠稳定性:结果:突变体酶的纯化效率为 77 倍,但回收率较低,仅为 0.7%。测定的动力学参数 Km、Vmax、kcat、比活度和催化效率分别为 13.96 (mM)、2.218 (mM/min)、273.9 (min-1)、237.8 (IU/mg) 和 19.62 (mM-1 min-1)。此外,用氯化胍诱导变性法测定突变体和商用 L-天冬酰胺酶的解折自由能分别为 8421 J/mol 和 5274 J/mol:结论:与野生型相比,突变型酶的稳定性有所提高。尽管表达水平和恢复能力较低,但突变型 L-天冬酰胺酶表现出了良好的活性和稳定性,具有潜在的临床和工业应用前景。
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引用次数: 0
Dual-stage Acting Dendrimeric Nanoparticle for Deepened Chemotherapeutic Drug Delivery to Tumor Cells. 双级作用树枝状聚合物纳米粒子用于加深对肿瘤细胞的化疗药物输送。
IF 3.1 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-01 Epub Date: 2024-06-29 DOI: 10.34172/apb.2024.054
Mohammad Shahpouri, Mohammad Amin Adili-Aghdam, Hossein Mahmudi, Saeedeh Ghiasvand, Hamed Dadashi, Aysan Salemi, Sajjad Alimohammadvand, Leila Roshangar, Abolfazl Barzegari, Mehdi Jaymand, Rana Jahanban-Esfahlan

Purpose: We report on the design of hypoxia-induced dual-stage acting dendrimeric nanoparticles (NPs) for selective delivery of two chemotherapeutic model drugs doxorubicin (DOX) and tirapazamin (TPZ) for deepened drug delivery into hypoxic tumors in vitro.

Methods: PAMAM G5 dendrimers were crosslinked with a hypoxic azo linker, attached to a mPEG to form a detachable corona on the dendrimer surface (PAP NPs). NPs were characterized by Zeta sizer, transmission electron microscope (TEM), Fourier transforms infrared (FTIR) and drug release kinetics. The anti-cancer performance of PAPs was evaluated by numerous tests in 2D and 3D cultured MDA-MB-231 breast cancer cells.

Results: MTT assay showed a significant difference between PAP and PAMAMG5 in terms of biocompatibility, and the effect of PAP@DOX was significantly greater than free DOX in hypoxic conditions. The results of DAPI and Annexin V-FITC/PI cell staining also confirmed uniform drug penetration as validated by induction of 90% cell apoptosis in spheroids and a high level of PAP@DOX-induced ROS generation under hypoxia conditions. Mechanistically, PAP@DOX significantly reduced the expression of mTOR, and Notch1, while the expression of Bax and Caspase3 was considerably unregulated, compared to the controls. Importantly, hypoxia-responsive disintegration and hypoxia-induced activation of HAP drug were synergized to promote deep and homogenous HAP distribution in whole microtumor regions to efficiently eliminate residual tumor cells.

Conclusion: Our results indicate the safety and high therapeutic potential of PAP system for targeted drug delivery of chemotherapeutics in particular HAPs which show maximum anti-cancer activity against hypoxic solid tumors.

目的:我们报告了缺氧诱导双级作用树枝状分子纳米颗粒(NPs)的设计,用于体外选择性递送两种化疗模型药物多柔比星(DOX)和替拉帕嗪(TPZ),以加深缺氧肿瘤的药物递送:方法:PAMAM G5树枝状聚合物与低氧偶氮连接剂交联,并与mPEG连接,在树枝状聚合物表面形成可分离的电晕(PAP NPs)。研究人员通过 Zeta 分析仪、透射电子显微镜(TEM)、傅立叶变换红外光谱(FTIR)和药物释放动力学对 NPs 进行了表征。通过在二维和三维培养的 MDA-MB-231 乳腺癌细胞中进行多项测试,评估了 PAPs 的抗癌性能:MTT试验表明,PAP与PAMAMG5在生物相容性方面存在显著差异,在缺氧条件下,PAP@DOX的效果明显高于游离DOX。DAPI和Annexin V-FITC/PI细胞染色结果也证实了药物的均匀渗透,球形细胞中90%的细胞凋亡诱导和缺氧条件下PAP@DOX诱导的高水平ROS生成也验证了这一点。从机理上讲,与对照组相比,PAP@DOX 能明显降低 mTOR 和 Notch1 的表达,而 Bax 和 Caspase3 的表达则明显不受调控。重要的是,缺氧反应性解体和缺氧诱导的HAP药物激活协同作用,促进了HAP在整个微小肿瘤区域的深层和均匀分布,从而有效消除残留的肿瘤细胞:我们的研究结果表明,PAP 系统用于化疗药物的靶向给药具有安全性和高治疗潜力,尤其是 HAPs 对缺氧性实体瘤具有最大的抗癌活性。
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引用次数: 0
Evaluating the Accuracy of Large Language Model (ChatGPT) in Providing Information on Metastatic Breast Cancer. 评估大型语言模型 (ChatGPT) 在提供转移性乳腺癌信息方面的准确性。
IF 3.1 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-01 Epub Date: 2024-07-31 DOI: 10.34172/apb.2024.060
Ramakrishna Gummadi, Nagasen Dasari, D Sathis Kumar, Sai Kiran S S Pindiprolu

Purpose: Artificial intelligence (AI), particularly large language models like ChatGPT developed by OpenAI, has demonstrated potential in various domains, including medicine. While ChatGPT has shown the capability to pass rigorous exams like the United States Medical Licensing Examination (USMLE) Step 1, its proficiency in addressing breast cancer-related inquiries-a complex and prevalent disease-remains underexplored. This study aims to assess the accuracy and comprehensiveness of ChatGPT's responses to common breast cancer questions, addressing a critical gap in the literature and evaluating its potential in enhancing patient education and support in breast cancer management.

Methods: A curated list of 100 frequently asked breast cancer questions was compiled from Cancer.net, the National Breast Cancer Foundation, and clinical practice. These questions were input into ChatGPT, and the responses were evaluated for accuracy by two primary experts using a four-point scale. Discrepancies in scoring were resolved through additional expert review.

Results: Of the 100 responses, 5 were entirely inaccurate, 22 partially accurate, 42 accurate but lacking comprehensiveness, and 31 highly accurate. The majority of the responses were found to be at least partially accurate, demonstrating ChatGPT's potential in providing reliable information on breast cancer.

Conclusion: ChatGPT shows promise as a supplementary tool for patient education on breast cancer. While generally accurate, the presence of inaccuracies underscores the need for professional oversight. The study advocates for integrating AI tools like ChatGPT in healthcare settings to support patient-provider interactions and health education, emphasizing the importance of regular updates to reflect the latest research and clinical guidelines.

目的:人工智能(AI),尤其是像 OpenAI 开发的 ChatGPT 这样的大型语言模型,已在包括医学在内的各个领域展现出潜力。虽然 ChatGPT 已显示出通过美国医学执业资格考试(USMLE)第 1 步等严格考试的能力,但它在处理乳腺癌相关咨询--一种复杂而普遍的疾病--方面的能力仍未得到充分探索。本研究旨在评估 ChatGPT 对常见乳腺癌问题回答的准确性和全面性,填补文献中的一个重要空白,并评估其在加强患者教育和支持乳腺癌管理方面的潜力:方法:从 Cancer.net、全美乳腺癌基金会和临床实践中整理出 100 个乳腺癌常见问题。这些问题被输入到 ChatGPT 中,并由两位主要专家使用四点量表对回复的准确性进行评估。评分中出现的差异通过额外的专家审核来解决:在 100 个回答中,5 个完全不准确,22 个部分准确,42 个准确但不够全面,31 个高度准确。大多数回复至少部分准确,这表明 ChatGPT 在提供可靠的乳腺癌信息方面具有潜力:结论:ChatGPT 有希望成为乳腺癌患者教育的辅助工具。虽然总体上是准确的,但不准确之处的存在凸显了专业监督的必要性。该研究提倡将 ChatGPT 等人工智能工具整合到医疗环境中,以支持患者与医护人员之间的互动和健康教育,并强调了定期更新以反映最新研究和临床指南的重要性。
{"title":"Evaluating the Accuracy of Large Language Model (ChatGPT) in Providing Information on Metastatic Breast Cancer.","authors":"Ramakrishna Gummadi, Nagasen Dasari, D Sathis Kumar, Sai Kiran S S Pindiprolu","doi":"10.34172/apb.2024.060","DOIUrl":"10.34172/apb.2024.060","url":null,"abstract":"<p><strong>Purpose: </strong>Artificial intelligence (AI), particularly large language models like ChatGPT developed by OpenAI, has demonstrated potential in various domains, including medicine. While ChatGPT has shown the capability to pass rigorous exams like the United States Medical Licensing Examination (USMLE) Step 1, its proficiency in addressing breast cancer-related inquiries-a complex and prevalent disease-remains underexplored. This study aims to assess the accuracy and comprehensiveness of ChatGPT's responses to common breast cancer questions, addressing a critical gap in the literature and evaluating its potential in enhancing patient education and support in breast cancer management.</p><p><strong>Methods: </strong>A curated list of 100 frequently asked breast cancer questions was compiled from Cancer.net, the National Breast Cancer Foundation, and clinical practice. These questions were input into ChatGPT, and the responses were evaluated for accuracy by two primary experts using a four-point scale. Discrepancies in scoring were resolved through additional expert review.</p><p><strong>Results: </strong>Of the 100 responses, 5 were entirely inaccurate, 22 partially accurate, 42 accurate but lacking comprehensiveness, and 31 highly accurate. The majority of the responses were found to be at least partially accurate, demonstrating ChatGPT's potential in providing reliable information on breast cancer.</p><p><strong>Conclusion: </strong>ChatGPT shows promise as a supplementary tool for patient education on breast cancer. While generally accurate, the presence of inaccuracies underscores the need for professional oversight. The study advocates for integrating AI tools like ChatGPT in healthcare settings to support patient-provider interactions and health education, emphasizing the importance of regular updates to reflect the latest research and clinical guidelines.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"14 3","pages":"499-503"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566303","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
Unveiling the Hidden Menace: A Topic Modeling Analysis of Hijacked Medical Journals. 揭开隐藏威胁的面纱:对被劫持医学期刊的主题建模分析。
IF 3.1 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-01 Epub Date: 2024-03-02 DOI: 10.34172/apb.2024.029
Mehdi Dadkhah, Mihály Hegedűs, Prema Nedungadi, Raghu Raman, Lóránt Dénes Dávid

Purpose: Nowadays, many studies discuss scholarly publishing and associated challenges, but the problem of hijacked journals has been neglected. Hijacked journals are cloned websites that mimic original journals but are managed by cybercriminals. The present study uses a topic modeling approach to analyze published papers in hijacked versions of medical journals.

Methods: A total of 3384 papers were downloaded from 21 hijacked journals in the medical domain and analyzed by topic modeling algorithm.

Results: Results indicate that hijacked versions of medical journals are published in most fields of the medical domain and typically respect the primary domain of the original journal.

Conclusion: The academic world is faced with the third-generation of hijacked journals, and their detection may be more complex than common ones. The usage of artificial intelligence (AI) can be a powerful tool to deal with the phenomenon.

目的:如今,许多研究都在讨论学术出版和相关挑战,但却忽视了期刊被劫持的问题。被劫持期刊是模仿原始期刊的克隆网站,但由网络犯罪分子管理。本研究采用主题建模法分析被劫持版医学期刊上发表的论文:方法:从医学领域的 21 种被劫持期刊中下载了共计 3384 篇论文,并通过主题建模算法进行分析:结果表明,被劫持的医学期刊发表的论文涉及医学领域的大部分领域,并且通常尊重原期刊的主要领域:结论:学术界面临着第三代劫持期刊,对它们的检测可能比普通期刊更复杂。使用人工智能(AI)是应对这一现象的有力工具。
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引用次数: 0
Xenogeneic Transplantation Promoted Human Exosome Sequestration in Rat Specific Organs 异种器官移植促进人类外泌体在大鼠特定器官中的封存
IF 3.6 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-12-04 DOI: 10.34172/apb.2024.022
Halimeh Mobarak, M. Mahdipour, Arshad Ghaffari-Nasab, R. Rahbarghazi
Purpose Exosomes (Exos) are introduced as novel cell-free therapeutics with multiple benefits alongside and/or over-cell therapy. Here, we aimed to study the distribution pattern of normal and cancer xenogeneic Exos and possible interspecies reactions in a rat model. Methods Exos were isolated from normal HUVECs and MDA-MB-231 breast cancer cells. Values like mean diameter size and zeta potential distribution were studied using DLS. The morphology of isolated Exos was monitored by SEM images. Using western blotting, protein levels of exosomal tetraspanins were detected. For the in vivo study, Dil-labeled normal and cancer Exos were injected into the tail vein (100 µg exosomal protein/rat) three times at 1-hour intervals. After 24 hours, rats were euthanized and the cellular uptake of Exos was monitored in different organs using immunofluorescence staining (IF). Results The size distribution and mean zeta potential of HUVEC and MDA-MB-231 cells Exos were 80 ± 29.94 and 64.77 ± 25.49 nm, and −7.58 and −11.8 mV, respectively. Western blotting revealed CD9, CD81, and CD63 in normal and cancer Exos. The SEM images exhibited typical nano-sized round-shape Exo particles. IF staining indicated sequestration of administrated Exos in splenic tissue and lungs. The distribution of Exo in kidneys, aorta, and hepatic tissue was less. These features were more evident in the group that received cancer Exos. We found no obvious adverse effects in rats that received normal or cancer Exos. Conclusion Data indicated that both normal and cancerous xenogeneic human Exos can be sequestrated prominently in splenic tissue and lungs. Novel delivery approaches and engineering tools are helpful in the target delivery of administrated Exos to the injured sites
外泌体(Exos)是一种新型的无细胞治疗药物,与过度细胞治疗一起具有多种益处。在这里,我们的目的是研究正常和癌症异种外显子的分布模式和可能的种间反应在大鼠模型中。方法从正常huvec细胞和MDA-MB-231乳腺癌细胞中分离Exos。用DLS研究了平均直径大小和zeta电位分布等值。利用扫描电镜对分离的Exos进行形态学观察。采用免疫印迹法检测外泌体四联蛋白的蛋白水平。在体内研究中,将dil标记的正常和癌症外泌体(100µg外泌体蛋白/大鼠)注射到尾静脉中,每隔1小时注射3次。24小时后,对大鼠实施安乐死,采用免疫荧光染色法(IF)监测Exos在不同器官的细胞摄取情况。结果HUVEC和MDA-MB-231细胞Exos的大小分布和平均zeta电位分别为80±29.94 nm和64.77±25.49 nm,−7.58 mV和−11.8 mV。Western blotting在正常和癌外显子中发现CD9、CD81和CD63。SEM图像显示典型的纳米级圆形Exo颗粒。IF染色显示给药的Exos在脾组织和肺中被隔离。Exo在肾脏、主动脉和肝组织中的分布较少。这些特征在接受癌症Exos治疗的组中更为明显。我们发现接受正常或癌症Exos的大鼠没有明显的不良反应。结论正常和癌变异种人外显子在脾组织和肺中均有明显的隔离。新的递送方法和工程工具有助于将给药Exos靶向递送到受伤部位
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引用次数: 0
Discrepancies in Open Access Fees within Pharmacology, Toxicology, and Pharmaceutics Journals. 药理学、毒理学和药剂学期刊开放获取费用的差异
IF 3.6 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-01 Epub Date: 2023-04-29 DOI: 10.34172/apb.2023.076
Rana M F Sammour, Aliasgar Shahiwala

Modern science has been transformed by open access (OA) publishing levied a significant economic burden on the authors. This article analyzes the discrepancies among OA publication fees in pharmacology, toxicology, and pharmaceutics. The observations comprise 160 OA journals and their corresponding Q ranking, SJR, H index, impact factor, country, and cost of publication. The OA fees were found to depend on the quality matrices, which was unexpected. Differences in OA fees raise ethical questions as OA fees are meant to cover the publication charges by the publishers or generate more revenues by taking advantage of the authors' temptation to publish in high-impact journals. Despite our findings being based on limited sample size and belonging to a particular field (pharmacy), it will shed considerable light on the issue of discrepancies among APCs charged by OA journals.

开放获取(OA)出版给作者带来了巨大的经济负担,从而改变了现代科学。根据Scimago的观点,本文分析了药理学、毒理学和药学学科领域OA费用之间的差异。观察结果包括160种OA期刊及其相应的Q排名、SJR、H指数、影响因素、国家和出版成本。OA费用取决于质量矩阵,而事实并非如此。OA费用的差异引发了道德问题,因为OA费用旨在支付出版商的出版费用,或通过利用作者在高影响力期刊上发表的诱惑来产生更多收入。尽管我们的研究结果是基于有限的样本量,并且属于特定的领域(药学),但它将对OA期刊收费的APC之间的差异问题提供相当多的线索。
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引用次数: 0
Human Mesenchymal Stem Cell Transplantation Improved Functional Outcomes Following Spinal Cord Injury Concomitantly with Neuroblast Regeneration. 人骨髓间充质干细胞移植改善脊髓损伤后的功能结果并伴有成神经细胞再生
IF 3.6 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-01 Epub Date: 2022-10-20 DOI: 10.34172/apb.2023.058
Maryam Lale Ataei, Mohammad Karimipour, Parviz Shahabi, Hamid Soltani-Zangbar, Maryam Pashaiasl

Purpose: Spinal cord injury (SCI) is damage to the spinal cord that resulted in irreversible neuronal loss, glial scar formation and axonal injury. Herein, we used the human amniotic fluid mesenchymal stem cells (hAF-MSCs) and their conditioned medium (CM), to investigate their ability in neuroblast and astrocyte production as well as functional recovery following SCI.

Methods: Fifty-four adult rats were randomly divided into nine groups (n=6), included: Control, SCI, (SCI + DMEM), (SCI + CM), (SCI + MSCs), (SCI + Astrocyte), (SCI + Astrocyte + DMEM), (SCI + Astrocyte + CM) and (SCI + Astrocyte + MSCs). Following laminectomy and SCI induction, DMEM, CM, MSCs, and astrocytes were injected. Western blot was performed to explore the levels of the Sox2 protein in the MSCs-CM. The immunofluorescence staining against doublecortin (DCX) and glial fibrillary acidic protein (GFAP) was done. Finally, Basso-Beattie-Brenham (BBB) locomotor test was conducted to assess the neurological outcomes.

Results: Our results showed that the MSCs increased the number of endogenous DCX-positive cells and decreased the number of GFAP-positive cells by mediating juxtacrine and paracrine mechanisms (P<0.001). Transplanted human astrocytes were converted to neuroblasts rather than astrocytes under influence of MSCs and CM in the SCI. Moreover, functional recovery indexes were promoted in those groups that received MSCs and CM.

Conclusion: Taken together, our data indicate the MSCs via juxtacrine and paracrine pathways could direct the spinal cord endogenous neural stem cells (NSCs) to the neuroblasts lineage which indicates the capability of the MSCs in the increasing of the number of DCX-positive cells and astrocytes decline.

目的:脊髓损伤(Spinal cord injury, SCI)是脊髓的损伤,导致不可逆的神经元丢失、胶质瘢痕形成和轴突损伤。在此,我们使用人羊水间充质干细胞(half - mscs)及其条件培养基(CM)来研究它们在脊髓损伤后神经母细胞和星形胶质细胞生成以及功能恢复方面的能力。方法:54只成年大鼠随机分为9组(n=6),分别为:对照组、SCI、(SCI + DMEM)、(SCI + CM)、(SCI + MSCs)、(SCI +星形胶质细胞)、(SCI +星形胶质细胞+ DMEM)、(SCI +星形胶质细胞+ CM)和(SCI +星形胶质细胞+ MSCs)。椎板切除术和脊髓损伤诱导后,注射DMEM、CM、MSCs和星形胶质细胞。western -blot检测MSCs-CM中Sox2蛋白的表达水平。对DCX和GFAP进行免疫荧光染色。最后采用BBB (Basso-Beattie-Brenham)运动测试评估神经系统预后。结果:我们的研究结果表明,MSCs通过介导近分泌和旁分泌机制,增加了内源性dcx阳性细胞的数量,减少了gap阳性细胞的数量(p< 0.001)。在骨髓间充质干细胞和骨髓间充质干细胞的影响下,移植的人星形胶质细胞转化为神经母细胞,而不是星形胶质细胞。此外,MSCs和CM组的功能恢复指标均有所提高。结论:综上所述,MSCs通过近分泌和旁分泌途径引导脊髓内源性神经干细胞(NSCs)向成神经细胞谱系转变,表明MSCs具有dcx阳性细胞数量增加和星形胶质细胞数量减少的能力。
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引用次数: 0
Translational challenges in cancer nanotherapy 癌症纳米治疗的转化挑战
Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-10-25 DOI: 10.34172/apb.2024.021
Ravi Kiran V V V Ammu, Kusuma Kumari Garikapati, Praveen T. Krishnamurthy, Bhadram Kalyan Chekraverthy
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引用次数: 0
期刊
Advanced pharmaceutical bulletin
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