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Anticancer Potential of Pineapple and its Bioactive Compound Bromelain. 菠萝及其生物活性化合物菠萝蛋白酶的抗癌潜力
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-12 DOI: 10.2174/0113816128303910240713180835
Davinder Kumar, Suchitra, Jyoti Mundlia, Shiv Kumar Yadav, Deepika Yadav, Navidha Aggarwal, Hitesh Chopra, Virender Kumar, Mohammad Amjad Kamal

Various ailments have been treated with pineapple [Ananas comosus (L.) Merr.] throughout medicinal history. Pineapple and its bioactive compound bromelain possess health-promoting benefits. Detailed information on the chemotherapeutic activities of pineapple and its bioactive compound bromelain is provided in this review, which analyses the current literature regarding their therapeutic potential in cancer. Research on disease models in cell cultures is the focus of much of the existing research. Several studies have demonstrated the benefits of pineapple extract and bromelain for in vitro and in vivo cancer models. Preliminary animal model results show promise, but they must be translated into the clinical setting. Research on these compounds represents a promising future direction and may be well-tolerated.

在医学史上,人们一直用菠萝(Ananas comosus (L.) Merr.)治疗各种疾病。菠萝及其生物活性化合物菠萝蛋白酶具有促进健康的功效。本综述提供了有关菠萝及其生物活性化合物菠萝蛋白酶化疗活性的详细信息,分析了有关其癌症治疗潜力的现有文献。细胞培养的疾病模型研究是现有研究的重点。一些研究已经证明了菠萝提取物和菠萝蛋白酶对体外和体内癌症模型的益处。初步的动物模型结果显示了前景,但这些结果必须转化到临床环境中。对这些化合物的研究是一个很有前景的未来方向,而且可能具有良好的耐受性。
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引用次数: 0
Improving Vaccine Response through Probiotics and Micronutrient Supplementation: Evaluating the Role of TLR5 in Adult Female BALB/c Mice. 通过补充益生菌和微量营养素改善疫苗反应:评估TLR5在成年雌性BALB/c小鼠中的作用
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-10 DOI: 10.2174/0113816128310203240823053538
Zohre Eftekhari, Delaram Doroud, Maryam Tajabadi-Ebrahimi, Fatemeh Kazemi-Lomedasht

Background: The role of probiotics and micronutrients in improving immune system function and response to vaccination has been proven. Hence, this study aimed to investigate the effects of probiotics enriched with micronutrients on the immunogenicity of PastoCovac® vaccine.

Methods: The probiotic supplement BioBoost® and PastoCovac® vaccine, which contain six expressed receptor-binding domains (RBD) and conjugated with tetanus toxin, were administered concurrently. The safety and efficacy were assessed by determining Immunoglobulin G (IgG) antibody titers to RBD and cytokines, mRNA expression of Toll-like Receptors (TLRs) 5, and clinical symptoms.

Results: Results revealed that the administration of the probiotics enriched with micronutrients and vitamins for 14 days before the first vaccine dose, followed by continued supplementation for 14 days after the first dose, and in conjunction with the second vaccine dose, yielded the most significant elevation in interleukin 4 (IL-4), Tumor Necrosis Factor-alpha (TNF alpha), Interferon-gamma (IFN-gamma), and anti-SARS-CoV-2 RBD IgG levels within the supernatant samples collected from spleen cultures with the highest expression of TLR5 genes in intestinal samples, compared to the control group.

Conclusion: Our results indicated that the inclusion of probiotics enriched with micronutrients and vitamins significantly enhanced the immunogenicity of the PastoCovac® vaccine. Based on the recommendation to administer third and fourth vaccine doses, particularly for vulnerable and elderly individuals, the utilization of supplements containing probiotics is expected to favorably influence immune responses.

背景:益生菌和微量营养素在改善免疫系统功能和疫苗接种反应方面的作用已得到证实。因此,本研究旨在探讨富含微量营养素的益生菌对PastoCovac®疫苗免疫原性的影响:方法:同时接种益生菌补充剂 BioBoost® 和 PastoCovac® 疫苗,后者含有六个表达的受体结合域 (RBD),并与破伤风毒素共轭。通过测定 RBD 和细胞因子的免疫球蛋白 G (IgG) 抗体滴度、Toll 样受体 (TLR) 5 的 mRNA 表达以及临床症状来评估疫苗的安全性和有效性:结果:结果显示,在接种第一剂疫苗前 14 天服用富含微量元素和维生素的益生菌,在接种第一剂疫苗后 14 天继续补充,并在接种第二剂疫苗的同时服用富含微量元素和维生素的益生菌、与对照组相比,从脾脏培养物收集的上清样本中白细胞介素 4 (IL-4)、肿瘤坏死因子-α (TNF alpha)、γ 干扰素 (IFN-gamma) 和抗 SARS-CoV-2 RBD IgG 水平的升高最为明显,肠道样本中 TLR5 基因的表达量最高。结论我们的研究结果表明,加入富含微量营养素和维生素的益生菌可显著增强 PastoCovac® 疫苗的免疫原性。根据接种第三和第四剂疫苗的建议,尤其是针对易感人群和老年人,使用含有益生菌的补充剂有望对免疫反应产生有利影响。
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引用次数: 0
Potential Signal Pathways and Therapeutic Effects of Mesenchymal Stem Cell on Oxidative Stress in Diseases. 间充质干细胞对疾病中氧化应激的潜在信号通路和治疗效果。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-10 DOI: 10.2174/0113816128308454240823074555
Yina Xie, Lingqian Zheng, Wenmin Chen, Yang Zeng, Kaijin Yao, Tianbiao Zhou

Oxidative stress is a biological stress response produced by the destruction of redox equilibrium in aerobic metabolism in organisms, which is closely related to the occurrence of many diseases. Mesenchymal stem cells (MSCs) have been found to improve oxidative stress injury in a variety of diseases, including arthritis, chronic obstructive pulmonary disease, asthma, multiple sclerosis, focal segmental glomerulosclerosis, diabetic nephropathy, ischemia-reperfusion injury, hepatic fibrosis, myocardial infarction, diabetes, inflammatory bowel disease, etc. The antioxidant stress capacity of MSCs may be a breakthrough in the treatment of these diseases. This review found that MSCs have the ability to resist oxidative stress, which may be achieved through MSCs involvement in mediating the Nrf2, MAPK, NF-κB, AMPK, PI3K/AKT and Wnt/b-catenin signaling pathways.

氧化应激是生物体有氧代谢中氧化还原平衡遭到破坏而产生的一种生物应激反应,与多种疾病的发生密切相关。研究发现,间充质干细胞(MSCs)可改善多种疾病的氧化应激损伤,包括关节炎、慢性阻塞性肺病、哮喘、多发性硬化、局灶节段性肾小球硬化、糖尿病肾病、缺血再灌注损伤、肝纤维化、心肌梗死、糖尿病、炎症性肠病等。间充质干细胞的抗氧化应激能力可能是治疗这些疾病的突破口。本综述发现,间充质干细胞具有抗氧化能力,这可能是通过间充质干细胞参与介导Nrf2、MAPK、NF-κB、AMPK、PI3K/AKT和Wnt/b-catenin信号通路实现的。
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引用次数: 0
Some Highly Potent Nepalese Medicinal Plants with Antimicrobial Properties 一些具有抗菌特性的强效尼泊尔药用植物
IF 3.1 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-10 DOI: 10.2174/0113816128309718240822060114
Asmita Khanal, Sabina Shrestha, Rameshwar Adhikari
: In recent years, microbial infections have emerged as a serious global health problem, necessitating the search for novel and effective treatments. Medicinal plants contain phytochemicals that can be used to prevent and treat various infections. Traditional medicinal practices have long relied on the healing properties of herbs, and Nepal is particularly rich in this knowledge. Bioactive compounds found in plants possess antibacterial, antifungal, and antiviral properties, making them a valuable resource for the fight against microbial infections. This review focuses on three medicinal plants native to Nepal, Amomum subulatum, Cymbopogon jwarancusa, and Cinnamomum glaucescens, which contain potent antimicrobial phytochemicals. The traditional uses, bioactive components, and biological activities of these plants are discussed, providing valuable insights into their potential as natural remedies to combat microbial infections.
:近年来,微生物感染已成为一个严重的全球健康问题,因此有必要寻找新颖有效的治疗方法。药用植物含有植物化学物质,可用于预防和治疗各种感染。长期以来,传统医学一直依赖草药的治疗特性,尼泊尔在这方面的知识尤为丰富。植物中发现的生物活性化合物具有抗菌、抗真菌和抗病毒的特性,使其成为抗击微生物感染的宝贵资源。本综述重点介绍尼泊尔的三种药用植物:Amomum subulatum、Cymbopogon jwarancusa 和 Cinnamomum glaucescens,它们都含有强效的抗微生物植物化学物质。本文讨论了这些植物的传统用途、生物活性成分和生物活性,为了解它们作为天然疗法对抗微生物感染的潜力提供了宝贵的见解。
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引用次数: 0
Alendronate for Effective Treatment of Male Osteoporosis : An Insight. 阿仑膦酸钠有效治疗男性骨质疏松症:透视。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-05 DOI: 10.2174/0113816128310838240820065324
Hanan Al Lawati, Sara Al Busaidi, Thuraiya Al Rawahi, Abdullah Al Lawati, Ahmed Kifah, Srijit Das

Osteoporosis is a major global health problem. The increase in the incidence of osteoporosis in the elderly poses a challenge to treat and also results in an economic burden for the nation. Osteoporosis has been given more importance in females, and there is an urgent need to address this disease in males. Various drugs, such as nitrogen-containing phosphonates, RANK ligand inhibitors, parathormones, and alendronate, have been used for effective treatment of osteoporosis. Alendronate (alendronic acid), a nitrogen-containing bisphosphonate that inhibits bone resorption by osteoclasts, was synthesized during the 1970s. In the present review, we discuss the pharmacokinetics, mechanism of action, adverse effects, contraindications, and toxicity monitoring of alendronate. The drug may be effectively used for the treatment of male osteoporosis in order to increase bone mineral density and prevent fractures.

骨质疏松症是一个重大的全球性健康问题。老年人骨质疏松症发病率的增加给治疗带来了挑战,也给国家造成了经济负担。女性骨质疏松症更受重视,而男性骨质疏松症则亟待解决。含氮膦酸盐、RANK 配体抑制剂、副激素和阿仑膦酸钠等多种药物已被用于有效治疗骨质疏松症。阿仑膦酸盐(阿仑膦酸)是一种含氮双膦酸盐,可抑制破骨细胞的骨吸收,于 20 世纪 70 年代合成。在本综述中,我们讨论了阿仑膦酸钠的药代动力学、作用机制、不良反应、禁忌症和毒性监测。该药物可有效用于治疗男性骨质疏松症,以增加骨矿密度和预防骨折。
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引用次数: 0
Harnessing Nanoparticles to Overcome Antimicrobial Resistance: Promises and Challenges. 利用纳米粒子克服抗菌剂耐药性:前景与挑战。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-29 DOI: 10.2174/0113816128326718240809091654
Akash Mishra, Anupam Jyoti, Krishna Aayush, Juhi Saxena, Kanika Sharma

The rise of antimicrobial resistance (AMR) has become a serious global health issue that kills millions of people each year globally. AMR developed in bacteria is difficult to treat and poses a challenge to clinicians. Bacteria develop resistance through a variety of processes, including biofilm growth, targeted area alterations, and therapeutic drug alteration, prolonging the period they remain within cells, where antibiotics are useless at therapeutic levels. This rise in resistance is linked to increased illness and death, highlighting the urgent need for effective solutions to combat this growing challenge. Nanoparticles (NPs) offer unique solutions for fighting AMR bacteria. Being smaller in size with a high surface area, enhancing interaction with bacteria makes the NPs strong antibacterial agents against various infections. In this review, we have discussed the epidemiology and mechanism of AMR development. Furthermore, the role of nanoparticles as antibacterial agents, and their role in drug delivery has been addressed. Additionally, the potential, challenges, toxicity, and future prospects of nanoparticles as antibacterial agents against AMR pathogens have been discussed. The research work discussed in this review links with Sustainable Development Goal 3 (SDG-3), which aims to ensure disease-free lives and promote well-being for all ages.

抗菌药耐药性(AMR)的增加已成为一个严重的全球健康问题,每年导致全球数百万人死亡。细菌产生的 AMR 难以治疗,给临床医生带来了挑战。细菌通过各种过程产生耐药性,包括生物膜生长、靶区改变和治疗药物改变,从而延长了细菌在细胞内的存活时间,使抗生素在治疗水平上失去作用。抗药性的增加与疾病和死亡的增加有关,因此迫切需要有效的解决方案来应对这一日益严峻的挑战。纳米粒子(NPs)为抗击 AMR 细菌提供了独特的解决方案。纳米粒子体积小、比表面积大,能增强与细菌的相互作用,是抗击各种感染的强力抗菌剂。在这篇综述中,我们讨论了 AMR 的流行病学和发展机制。此外,还讨论了纳米粒子作为抗菌剂的作用及其在药物输送中的作用。此外,我们还讨论了纳米粒子作为抗菌剂对抗 AMR 病原体的潜力、挑战、毒性和未来前景。本综述中讨论的研究工作与可持续发展目标 3(SDG-3)相关联,该目标旨在确保无疾病生活并促进所有年龄段的人的福祉。
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引用次数: 0
In-silico Studies and Antioxidant and Neuroprotective Assessment of Microencapsulated Celecoxib against Scopolamine-induced Alzheimer's Disease. 微胶囊塞来昔布针对东莨菪碱诱发的阿尔茨海默病的分子内研究及抗氧化和神经保护评估
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-28 DOI: 10.2174/0113816128298289240723103828
Rajendra Herur Vishnumurthy, M Gnana Ruba Priya, Prashant Tiwari, Viswas Raja Solomon

Background and objective: Alzheimer's Disease (AD) is an enervating and chronic progressive neurodegenerative disorder. Celecoxib (CXB) possesses efficacious antioxidants and has neuroprotective, anti- inflammatory, and immunomodulatory properties. However, the poor bioavailability of CXB limits its therapeutic utility. Thus, this study aimed to evaluate the microencapsulated celecoxib MCXB) for neuroprotection.

Methodology: CXB was screened by molecular docking study using AutoDock (version 5.2), and the following proteins, such as 4EY7, 2HM1, 2Z5X, and 1PBQ were selected for predicting its neuroprotective effect. Scopolamine 20 mg/kg/day for approximately 7 days was administered to albino rats. Pure CXB 100 mg/kg/- day and 200 mg/kg/day, and MCXB 100 mg/kg/day and 200 mg/kg/day were administered, respectively. Further, to assess the oxidative stress, the nitric oxide (NO), superoxide dismutase (SOD), catalase, and lipid peroxidation (LPO) were evaluated using chemical methods. The neurochemical biomarkers like AChE, glutamate, and dopamine were evaluated using the ELISA method. Further, the histopathology of brain cells was carried out to assess the neuro-regeneration and neurodegeneration of the neurons.

Results: There was a significant binding interaction of CXB (score -6.3, -6.5, -5.1, -9.1) and donepezil (score- 5.5, -7.6, -7.0, and -8.6) with AchE (4EY7), β-secretase (2HM1, monoamine oxidase (2Z5X), and glutamate (1PBQ), respectively. MCXB-treated rats (100 mg/kg/day, 200 mg/kg/day) showed increased SOD levels (p < 0.001), whereas NO, catalase, and LPO levels were significantly (p < 0.001) decreased as compared to scopolamine-treated rats. Further, MCXB-treated rats showed a modulatory effect in the level of dopamine and AchE. However, the glutamate level was significantly (p < 0.001) decreased.

Conclusion: In addition to that, histopathological examination of the hippocampus part showed remarkable improvement in brain cells. So, the findings of the results revealed that MCXB, in a dose-dependent manner, showed a neuroprotective effect against scopolamine-induced AD. This effect may be attributed to the activation of cholinergic pathways.

背景和目的:阿尔茨海默氏症(AD)是一种慢性进行性神经退行性疾病。塞来昔布(CXB)是一种有效的抗氧化剂,具有神经保护、抗炎和免疫调节特性。然而,塞来昔布的生物利用度较低,限制了其治疗作用。因此,本研究旨在评估微囊塞来昔布(MCXB)的神经保护作用:使用 AutoDock(5.2 版)进行分子对接研究,筛选出 4EY7、2HM1、2Z5X 和 1PBQ 等蛋白质用于预测 CXB 的神经保护作用。给白化大鼠注射东莨菪碱 20 毫克/千克/天,持续约 7 天。分别给予纯 CXB 100 毫克/千克/天和 200 毫克/千克/天,以及 MCXB 100 毫克/千克/天和 200 毫克/千克/天。此外,为了评估氧化应激,还使用化学方法评估了一氧化氮(NO)、超氧化物歧化酶(SOD)、过氧化氢酶和脂质过氧化物(LPO)。使用 ELISA 方法评估了 AChE、谷氨酸和多巴胺等神经化学生物标志物。此外,还对脑细胞进行了组织病理学检查,以评估神经元的神经再生和神经退化情况:结果:CXB(得分-6.3、-6.5、-5.1、-9.1)和多奈哌齐(得分-5.5、-7.6、-7.0、-8.6)分别与 AchE(4EY7)、β-分泌酶(2HM1)、单胺氧化酶(2Z5X)和谷氨酸(1PBQ)有明显的结合相互作用。与东莨菪碱处理的大鼠相比,MCXB(100 毫克/千克/天、200 毫克/千克/天)处理的大鼠的 SOD 水平升高(p < 0.001),而 NO、过氧化氢酶和 LPO 水平则显著降低(p < 0.001)。此外,经 MCXB 处理的大鼠对多巴胺和 AchE 水平有调节作用。结论:MCXB 对大鼠的组织病理学研究结果表明,MCXB 对大鼠的多巴胺和 AchE 水平有调节作用,但谷氨酸水平明显下降(p < 0.001):此外,海马部分的组织病理学检查显示脑细胞有明显改善。因此,研究结果表明,MCXB 对东莨菪碱诱导的注意力缺失症具有神经保护作用。这种效应可能归因于胆碱能通路的激活。
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引用次数: 0
Murraya koenigii (L.) Spreng. as a Natural Intervention for Diabesity: A Review Murraya koenigii (L.) Spreng.作为治疗肥胖症的自然干预措施:综述
IF 3.1 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-28 DOI: 10.2174/0113816128304471240801183021
Sanjay Madhukar Jachak, Mridula Singh Thakur, Pallavi Ahirrao, Alok Goyal
Background: Murraya koenigii (L.) Spreng. (family: Rutaceae), commonly known as curry leaf or sweet neem, is a tropical plant native to India and Southeast Asia. It is highly valued in Ayurveda for its medicinal properties. Almost every part (fresh leaves, fruits, bark, and roots) of this plant is used to treat various ailments. Its fresh leaves are considered to have numerous medicinal properties for various diseases, including piles, inflammation, itching, fresh cuts, dysentery, and edema. A combination of curry leaf and buttermilk is used to treat diseases, such as amoebiasis, diabetes, and hepatitis. Its leaves are also believed to possess antioxidant, anti-inflammatory, and antimicrobial properties. The bark has been traditionally used for treating snakebites. Its roots are utilized in Ayurveda for the treatment of body aches. Being a storehouse of carbazole alkaloids, M. koenigii has been reported to show anti-obesity and anti-diabetic activity in in vitro and in vivo studies. The review aimed to appraise the role of M. koenigii leaf in the prevention of diabesity. Methods: We performed a literature search with the keywords “diabesity”, “obesity”, “diabetes”, “adipose tissue”, and “carbazole alkaloids” on Google Scholar, PubMed, and ScienceDirect databases. Several in vitro and in vivo studies conducted on cell lines and animals for anti-diabetic/anti-hyperglycemic and antihyperlipidemic activities have been included and appraised in the article, providing supporting evidence for the ethnomedicinal claims. Results and Conclusion: This review has been an attempt to summarize comprehensively the overall research done on M. koenigii with regard to obesity and diabetes. The studies on anti-diabetic/anti-hyperglycemic and anti-hyperlipidemic activities of the plant have ranged from studies on crude extracts to isolated compounds. However, some of the studies require further in-depth analysis and validation of obtained results.
背景介绍Murraya koenigii (L.) Spreng.(芸香科),俗称咖喱叶或甜楝树,是一种原产于印度和东南亚的热带植物。在阿育吠陀中,它的药用价值很高。这种植物的几乎每个部分(鲜叶、果实、树皮和根)都可用于治疗各种疾病。它的鲜叶被认为对痔疮、炎症、瘙痒、新伤口、痢疾和水肿等各种疾病具有多种药用功效。咖喱叶与酪乳的组合可用于治疗阿米巴病、糖尿病和肝炎等疾病。人们还认为咖喱叶具有抗氧化、消炎和抗菌的功效。树皮传统上用于治疗蛇咬伤。其根部在阿育吠陀中用于治疗身体疼痛。据报道,作为咔唑生物碱的宝库,M. koenigii 在体外和体内研究中显示出抗肥胖和抗糖尿病活性。本综述旨在评估鹅掌楸叶在预防肥胖症方面的作用。方法:我们在 Google Scholar、PubMed 和 ScienceDirect 数据库中以 "肥胖症"、"肥胖"、"糖尿病"、"脂肪组织 "和 "咔唑生物碱 "为关键词进行了文献检索。文章纳入并评估了在细胞系和动物身上进行的几项抗糖尿病/抗高血糖和抗高血脂活性的体外和体内研究,为民族药用声称提供了佐证。结果与结论:本综述试图全面总结有关柯尼希菌在肥胖症和糖尿病方面的整体研究。有关该植物抗糖尿病/抗高血糖和抗高血脂活性的研究包括粗提取物研究和分离化合物研究。然而,其中一些研究还需要进一步深入分析和验证所获得的结果。
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引用次数: 0
Activin A-Targeted Therapy in Cancer: An Updated Review on Challenges and Opportunities in Clinical Translation 癌症中的激活素 A 靶向疗法:关于临床转化的挑战与机遇的最新综述
IF 3.1 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-28 DOI: 10.2174/0113816128320120240805104433
Nima Rastegar-Pouyani, Mohammad Amin Farzin, Pegah Karimi, Sedighe Kolivand, Emad Jafarzadeh, Mohadeseh Haji Abdolvahab, Masoud Najafi
Activin A (ActA) is a cytokine from the TGF-β superfamily that mediates a vast number of physiological mechanisms, mainly through the SMAD signaling pathway. Growing evidence indicates that ActA overexpression is also correlated with poor prognosis in cancer patients and several tumor characteristics, including cancer proliferation, metastasis, immunosuppression, drug resistance, cachexia, and cancer-associated fibroblast activation. As such, ActA-targeted therapy has been viewed as a potential adjuvant therapy alongside other anti-cancer modalities that may result in more efficient anti-cancer effects, such as stronger immune responses, overcoming drug resistance, reversing cachexia, etc. However, despite its interesting concept, targeting ActA is not without certain challenges and considerations. Indeed, ActA has unexpectedly shown anti-tumor effects in some cases, which might be explained by differences in the expression levels of different ActA receptors on the cell surface, activation of non-SMAD pathways, and imbalance in ActA levels. Besides, many of the current ActA antagonists lack enough specificity and, as a result, bind to non-ActA receptors as well. Furthermore, ubiquitous expression of ActA in the body can cause serious adverse effects following systemic administration. Furthermore, to address these issues, anti-ActA monoclonal antibodies and nanoparticle drug delivery systems have recently been suggested to target ActA with better precision in the affected area. In this review, first, we provide the different implications of ActA in cancer. Then, we discuss the recent insights into targeting ActA signaling as an adjuvant therapy alongside other anti-cancer modalities, as well as the possible challenges and novel opportunities on the path of clinical translation.
激活素 A(ActA)是 TGF-β 超家族中的一种细胞因子,主要通过 SMAD 信号通路介导大量生理机制。越来越多的证据表明,ActA 的过表达与癌症患者的不良预后以及癌症增殖、转移、免疫抑制、耐药性、恶病质和癌症相关成纤维细胞激活等多种肿瘤特征相关。因此,ActA 靶向疗法被视为一种潜在的辅助疗法,可与其他抗癌方式一起产生更有效的抗癌效果,如更强的免疫反应、克服耐药性、逆转恶病质等。然而,尽管其概念很有趣,但以 ActA 为靶点并非没有一定的挑战和考虑因素。事实上,ActA 在某些情况下会意外地显示出抗肿瘤效果,这可能是由于细胞表面不同 ActA 受体的表达水平存在差异、非 SMAD 通路被激活以及 ActA 水平失衡等原因造成的。此外,目前许多 ActA 拮抗剂缺乏足够的特异性,因此也会与非 ActA 受体结合。此外,ActA 在体内的普遍表达会在全身用药后产生严重的不良反应。此外,为了解决这些问题,最近有人提出了抗ActA单克隆抗体和纳米颗粒给药系统,以更精确地靶向ActA受累区域。在这篇综述中,我们首先介绍了 ActA 对癌症的不同影响。然后,我们将讨论针对 ActA 信号与其他抗癌方法一起作为辅助疗法的最新见解,以及在临床转化道路上可能面临的挑战和新机遇。
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引用次数: 0
Magnesium (Mg2+): Essential Mineral for Neuronal Health: From Cellular Biochemistry to Cognitive Health and Behavior Regulation 镁(Mg2+):神经元健康的必需矿物质:从细胞生物化学到认知健康和行为调节
IF 3.1 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-27 DOI: 10.2174/0113816128321466240816075041
Aakash Kumar, Sidharth Mehan, Aarti Tiwari, Zuber Khan, Ghanshyam Das Gupta, Acharan S. Narula, Rajaram Samant
Magnesium (Mg2+) is a crucial mineral involved in numerous cellular processes critical for neuronal health and function. This review explores the multifaceted roles of Mg2+, from its biochemical interactions at the cellular level to its impact on cognitive health and behavioral regulation. Mg2+ acts as a cofactor for over 300 enzymatic reactions, including those involved in ATP synthesis, nucleic acid stability, and neurotransmitter release. It regulates ion channels, modulates synaptic plasticity, and maintains the structural integrity of cell membranes, which are essential for proper neuronal signaling and synaptic transmission. Recent studies have highlighted the significance of Mg2+ in neuroprotection, showing its ability to attenuate oxidative stress, reduce inflammation, and mitigate excitotoxicity, thereby safeguarding neuronal health. Furthermore, Mg2+ deficiency has been linked to a range of neuropsychiatric disorders, including depression, anxiety, and cognitive decline. Supplementation with Mg2+, particularly in the form of bioavailable compounds such as Magnesium-L-Threonate (MgLT), Magnesium-Acetyl-Taurate (MgAT), and other Magnesium salts, has shown some promising results in enhancing synaptic density, improving memory function, and alleviating symptoms of mental health disorders. This review highlights significant current findings on the cellular mechanisms by which Mg2+ exerts its neuroprotective effects and evaluates clinical and preclinical evidence supporting its therapeutic potential. By elucidating the comprehensive role of Mg2+ in neuronal health, this review aims to underscore the importance of maintaining optimal Mg2+ levels for cognitive function and behavioral regulation, advocating for further research into Mg2+ supplementation as a viable intervention for neuropsychiatric and neurodegenerative conditions.
镁(Mg2+)是一种重要的矿物质,它参与了许多对神经元健康和功能至关重要的细胞过程。本综述探讨了 Mg2+ 的多方面作用,从其在细胞水平的生化相互作用到其对认知健康和行为调节的影响。Mg2+ 是 300 多种酶促反应的辅助因子,包括参与 ATP 合成、核酸稳定性和神经递质释放的反应。它还能调节离子通道、调节突触的可塑性,并保持细胞膜结构的完整性,这对神经元信号的正常传递和突触传输至关重要。最近的研究强调了 Mg2+ 在神经保护中的重要作用,表明它能够减轻氧化应激、减少炎症和减轻兴奋毒性,从而保护神经元的健康。此外,Mg2+ 缺乏还与一系列神经精神疾病有关,包括抑郁症、焦虑症和认知能力下降。补充 Mg2+,特别是以生物可利用化合物的形式补充 Mg2+,如柠檬酸镁(MgLT)、乙酰牛磺酸镁(MgAT)和其他镁盐,在增强突触密度、改善记忆功能和缓解精神疾病症状方面取得了一些有希望的结果。本综述重点介绍了目前关于 Mg2+ 发挥神经保护作用的细胞机制的重要发现,并评估了支持其治疗潜力的临床和临床前证据。通过阐明 Mg2+ 在神经元健康中的综合作用,本综述旨在强调维持最佳 Mg2+ 水平对认知功能和行为调节的重要性,倡导进一步研究 Mg2+ 补充剂,将其作为治疗神经精神疾病和神经退行性疾病的可行干预措施。
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Current pharmaceutical design
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