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Calycosin Enhances Heat Shock Related-Proteins in H9c2 Cells to Modulate Survival and Apoptosis against Heat Shock. 萼萼素能增强 H9c2 细胞中的热休克相关蛋白,从而调节细胞的存活和凋亡,抵御热休克。
Pub Date : 2024-01-01 Epub Date: 2024-06-28 DOI: 10.1142/S0192415X24500472
Pei-Fang Lai, Ramasamy Mahendran, Bruce Chi-Kang Tsai, Cheng-You Lu, Chia-Hua Kuo, Kuan-Ho Lin, Shang-Yeh Lu, Yu-Ling Wu, Yung-Ming Chang, Wei-Wen Kuo, Chih-Yang Huang

Heat shock proteins (HSPs), which function as chaperones, are activated in response to various environmental stressors. In addition to their role in diverse aspects of protein production, HSPs protect against harmful protein-related stressors. Calycosin exhibits numerous beneficial properties. This study aims to explore the protective effects of calycosin in the heart under heat shock and determine its underlying mechanism. H9c2 cells, western blot, TUNEL staining, flow cytometry, and immunofluorescence staining were used. The time-dependent effects of heat shock analyzed using western blot revealed increased HSP expression for up to 2[Formula: see text]h, followed by protein degradation after 4[Formula: see text]h. Hence, a heat shock damage duration of 4[Formula: see text]h was chosen for subsequent investigations. Calycosin administered post-heat shock demonstrated dose-dependent recovery of cell viability. Under heat shock conditions, calycosin prevented the apoptosis of H9c2 cells by upregulating HSPs, suppressing p-JNK, enhancing Bcl-2 activation, and inhibiting cleaved caspase 3. Calycosin also inhibited Fas/FasL expression and activated cell survival markers (p-PI3K, p-ERK, p-Akt), indicating their cytoprotective properties through PI3K/Akt activation and JNK inhibition. TUNEL staining and flow cytometry confirmed that calycosin reduced apoptosis. Moreover, calycosin reversed the inhibitory effects of quercetin on HSF1 and Hsp70 expression, illustrating its role in enhancing Hsp70 expression through HSF1 activation during heat shock. Immunofluorescence staining demonstrated HSF1 translocation to the nucleus following calycosin treatment, emphasizing its cytoprotective effects. In conclusion, calycosin exhibits pronounced protective effects against heat shock-induced damages by modulating HSP expression and regulating key signaling pathways to promote cell survival in H9c2 cells.

热休克蛋白(HSP)具有伴侣蛋白的功能,可在各种环境压力下被激活。除了在蛋白质生产的不同方面发挥作用外,热休克蛋白还能抵御与蛋白质有关的有害应激源。萼萼素有许多有益的特性。本研究旨在探讨热休克条件下钙调素对心脏的保护作用,并确定其潜在机制。研究采用了 H9c2 细胞、Western 印迹、TUNEL 染色、流式细胞术和免疫荧光染色等方法。利用 Western 印迹分析了热休克的时间依赖性效应,发现 HSP 的表达在 2[式中:见正文]小时内增加,4[式中:见正文]小时后蛋白质降解。因此,后续研究选择的热休克损伤持续时间为 4[式中:见正文]小时。热休克后服用钙佐辛可使细胞活力得到恢复,但这与剂量有关。在热休克条件下,卡利科辛通过上调 HSPs、抑制 p-JNK、增强 Bcl-2 激活和抑制裂解的 caspase 3 来防止 H9c2 细胞凋亡。Calycosin还能抑制Fas/FasL的表达,激活细胞存活标志物(p-PI3K、p-ERK、p-Akt),表明它们通过激活PI3K/Akt和抑制JNK具有细胞保护特性。TUNEL 染色和流式细胞术证实钙黄绿素能减少细胞凋亡。此外,钙黄素还逆转了槲皮素对HSF1和Hsp70表达的抑制作用,说明它在热休克过程中通过激活HSF1增强了Hsp70的表达。免疫荧光染色显示,在钙黄素处理后,HSF1转位到细胞核,这强调了钙黄素的细胞保护作用。总之,钙黄素通过调节HSP的表达和关键信号通路来促进H9c2细胞的存活,对热休克诱导的损伤具有明显的保护作用。
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引用次数: 0
The Effectiveness of Traditional Chinese Medicine in Treating Malignancies via Regulatory Cell Death Pathways and the Tumor Immune Microenvironment: A Review of Recent Advances. 中医药通过调控细胞死亡途径和肿瘤免疫微环境治疗恶性肿瘤的疗效:最新进展综述》。
Pub Date : 2024-01-01 Epub Date: 2024-02-07 DOI: 10.1142/S0192415X2450006X
Jingya Fu, Xiaoxia Xie, Huimin Yao, Haijuan Xiao, Zhuoqun Li, Zhenzhi Wang, Ran Ju, Yan Zhao, Zhijun Liu, Nana Zhang

Traditional Chinese Medicine (TCM) has achieved high clinical efficacy in treating malignancies in recent years and is thus gradually becoming an important therapy for patients with advanced tumor for its benefits in reducing side effects and improving patients' immune status. However, it has not been internationally recognized for cancer treatment because TCM's anti-tumor mechanism is not fully elucidated, limiting its clinical application and international promotion. This review traced the mechanism of the TCM-mediated tumor cell death pathway and its effect on remodeling the tumor immune microenvironment, its direct impact on the microenvironment, its anti-tumor effect in combination with immunotherapy, and the current status of clinical application of TCM on tumor treatment. TCM can induce tumor cell death in many regulatory cell death (RCD) pathways, including apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. In addition, TCM-induced cell death could increase the immune cells' infiltration with an anti-tumor effect in the tumor tissue and elevate the proportion of these cells in the spleen or peripheral blood, enhancing the anti-tumor capacity of the tumor-bearing host. Moreover, TCM can directly affect immune function by increasing the population or activating the sub-type immune cells with an anti-tumor role. It was concluded that TCM could induce a pan-tumor death modality, remodeling the local TIME differently. It can also improve the systemic immune status of tumor-bearing hosts. This review aims to establish a theoretical basis for the clinical application of TCM in tumor treatment and to provide a reference for TCM's potential in combination with immunotherapy in cancer treatment.

近年来,中医药在治疗恶性肿瘤方面取得了较高的临床疗效,并因其在减轻副作用、改善患者免疫状态等方面的优势,逐渐成为晚期肿瘤患者的重要治疗手段。然而,由于中医药抗肿瘤机制尚未完全阐明,其在肿瘤治疗方面尚未得到国际认可,限制了其临床应用和国际推广。本综述追溯了中药介导肿瘤细胞死亡途径的机制及其对肿瘤免疫微环境的重塑作用、中药对肿瘤微环境的直接影响、中药联合免疫治疗的抗肿瘤作用以及中药治疗肿瘤的临床应用现状。中药可通过多种调节性细胞死亡(RCD)途径诱导肿瘤细胞死亡,包括凋亡、自噬、热凋亡、坏死和铁凋亡。此外,中药诱导的细胞死亡可增加肿瘤组织中具有抗肿瘤作用的免疫细胞浸润,并提高这些细胞在脾脏或外周血中的比例,增强肿瘤宿主的抗肿瘤能力。此外,中药还能直接影响免疫功能,增加或激活具有抗肿瘤作用的亚型免疫细胞的数量。研究认为,中药可诱导泛肿瘤死亡模式,对局部TIME进行不同程度的重塑。它还能改善肿瘤宿主的全身免疫状态。本综述旨在为中药在肿瘤治疗中的临床应用建立理论基础,并为中药与免疫疗法在肿瘤治疗中的结合潜力提供参考。
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引用次数: 0
Ferroptosis: A New Research Direction of Artemisinin and Its Derivatives in Anti-Cancer Treatment. 青蒿素及其衍生物在抗癌治疗中的新研究方向青蒿素及其衍生物在抗癌治疗中的新研究方向
Pub Date : 2024-01-01 Epub Date: 2024-02-07 DOI: 10.1142/S0192415X24500071
Youke Wang, Xiang Yuan, Min Ren, Zhiyu Wang

Ferroptosis, an iron-dependent cell death mechanism driven by an accumulation of lipid peroxides on cellular membranes, has emerged as a promising strategy to treat various diseases, including cancer. Ferroptosis inducers not only exhibit cytotoxic effects on multiple cancer cells, including drug-resistant cancer variants, but also hold potential as adjuncts to enhance the efficacy of other anti-cancer therapies, such as immunotherapy. In addition to synthetic inducers, natural compounds, such as artemisinin, can be considered ferroptosis inducers. Artemisinin, extracted from Artemisia annua L., is a poorly water-soluble antimalarial drug. For clinical applications, researchers have synthesized various water-soluble artemisinin derivatives such as dihydroartemisinin, artesunate, and artemether. Artemisinin and artemisinin derivatives (ARTEs) upregulate intracellular free iron levels and promote the accumulation of intracellular lipid peroxides to induce cancer cell ferroptosis, alleviating cancer development and resulting in strong anti-cancer effects in vitro and in vivo. In this review, we introduce the mechanisms of ferroptosis, summarize the research on ARTEs-induced ferroptosis in cancer cells, and discuss the clinical research progress and current challenges of ARTEs in anti-cancer treatment. This review deepens the current understanding of the relationship between ARTEs and ferroptosis and provides a theoretical basis for the clinical anti-cancer application of ARTEs in the future.

铁中毒是一种由细胞膜上脂质过氧化物积累驱动的铁依赖性细胞死亡机制,已成为治疗包括癌症在内的各种疾病的一种有前途的策略。铁氧化诱导剂不仅对多种癌细胞(包括耐药性癌症变种)具有细胞毒性作用,而且还具有作为辅助药物提高免疫疗法等其他抗癌疗法疗效的潜力。除合成诱导剂外,青蒿素等天然化合物也可被视为铁突变诱导剂。青蒿素提取自黄花蒿,是一种水溶性很差的抗疟药物。为了临床应用,研究人员合成了各种水溶性青蒿素衍生物,如双氢青蒿素、青蒿琥酯和蒿甲醚。青蒿素和青蒿素衍生物(ARTEs)可上调细胞内游离铁水平,促进细胞内脂质过氧化物的积累,从而诱导癌细胞铁变态反应,缓解癌症的发展,在体外和体内产生强大的抗癌作用。在这篇综述中,我们介绍了铁突变的机制,总结了 ARTEs 诱导癌细胞铁突变的研究,并讨论了 ARTEs 在抗癌治疗中的临床研究进展和目前面临的挑战。这篇综述加深了目前人们对 ARTEs 与铁突变之间关系的理解,并为 ARTEs 未来的临床抗癌应用提供了理论依据。
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引用次数: 0
Natural Bioactive Compounds: Emerging Therapies for Hyperuricemia. 天然生物活性化合物:治疗高尿酸血症的新疗法。
Pub Date : 2024-01-01 Epub Date: 2024-11-19 DOI: 10.1142/S0192415X24500733
Yafei Liu, Kaifeng Zheng, Huanhuan Wang, Hong Liu, Kunyang Zheng, Junjun Zhang, Liang Han, Shenghao Tu, Yaoxian Wang

Hyperuricemia is a crucial feature of metabolic syndrome, characterized by elevated uric acid that causes urate crystal deposits in joints, kidneys, and subcutaneous tissues, resulting in gout and hyperuricemic nephropathy. The primary causes of uric acid metabolism disorder include overproduction and reduced excretion. The majority of uric acid in human body is derived from the breakdown of purine nucleotides. Overproduction of uric acid can result from increased concentration or activity of xanthine oxidase, the key enzyme responsible for uric acid synthesis. Alterations in the activity of proteins responsible for uric acid reabsorption and excretion can also affect serum uric acid. Many bioactive compounds derived from natural plants have been shown to inhibit xanthine oxidase activity to reduce uric acid production, modulate the activity of transport proteins to promote uric acid excretion, or alleviate oxidative stress and inflammation through various signaling pathways. These properties have garnered significant attention from researchers. In this paper, we first introduce the pathophysiological mechanisms of hyperuricemia, then summarize bioactive compounds with urate-lowering effects, and discuss their potential applications in treating hyperuricemia and its complications.

高尿酸血症是代谢综合征的一个重要特征,其特点是尿酸升高,导致尿酸盐结晶沉积在关节、肾脏和皮下组织,引起痛风和高尿酸血症肾病。尿酸代谢紊乱的主要原因包括尿酸生成过多和排泄减少。人体内的尿酸大部分来自嘌呤核苷酸的分解。尿酸合成的关键酶黄嘌呤氧化酶的浓度或活性增加会导致尿酸生成过多。负责尿酸重吸收和排泄的蛋白质的活性改变也会影响血清尿酸。许多从天然植物中提取的生物活性化合物已被证明可抑制黄嘌呤氧化酶的活性以减少尿酸的产生,调节转运蛋白的活性以促进尿酸的排泄,或通过各种信号途径减轻氧化应激和炎症。这些特性引起了研究人员的极大关注。本文首先介绍了高尿酸血症的病理生理机制,然后总结了具有降尿酸作用的生物活性化合物,并讨论了它们在治疗高尿酸血症及其并发症方面的潜在应用。
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引用次数: 0
Acupuncture: A Review of the Safety and Adverse Events and the Strategy of Potential Risk Prevention. 针灸:针灸的安全性、不良事件及潜在风险预防策略综述。
Pub Date : 2024-01-01 Epub Date: 2024-10-26 DOI: 10.1142/S0192415X24500617
Chien-Chen Huang, Peddanna Kotha, Cheng-Hao Tu, Ming-Cheng Huang, Yi-Hung Chen, Jaung-Geng Lin

Acupuncture is widely accepted as a therapeutic treatment by patients and healthcare providers globally. The safety record has been well established in acupuncture practice although some rare adverse events (AEs) were reported in the literature. While acupuncture-related AEs are generally defined as any undesirable event that occurs in patients during acupuncture treatment that may or may not be associated with the treatment, acupuncture-related adverse reactions (ARs) are defined as any undesirable or harmful reaction induced by trained practitioners practicing acupuncture treatment with standard doses. In this review, we clarify the relationship between AEs and ARs. Furthermore, we compile a list of acupuncture-related AEs reported in systematic reviews and meta-analysis articles. We find that serious acupuncture-related AEs are rare, with serious AEs occurring at a rate of approximately 0.04-0.08 per 10,000 treatments. The most likely serious AEs are pneumothorax, central and peripheral nerve injuries, heart injuries, abdominal organ injuries, infections, and needle breakage. Commonly reported minor AEs include bruising, hematoma, or bleeding at the needling site, as well as vasovagal reactions such as tiredness, dizziness, fainting, or residual pain at insertion points. The analysis identifies contributing factors for serious AEs being deep needle penetration, incorrect acupoint selection, and improper needle manipulation. It also addresses infections caused by contaminated needles, environmental factors, and inadequate skin disinfection. Moreover, other serious AEs, like needle breakage, are mostly due to aggressive manipulation and repeated reheating. Importantly, most acupuncture-related AEs are preventable. To avoid such AEs, acupuncturists in clinical practice should carefully select needling areas, be aware of cautions and contraindications of acupuncture, maintain safe acupuncture depth and hygiene, and strictly adhere to standard operating procedures.

针灸作为一种治疗方法已被全球患者和医疗机构广泛接受。尽管文献报道了一些罕见的不良事件(AEs),但针灸实践中的安全记录已经得到了很好的证实。针灸相关不良反应(ARs)是指经过培训的针灸医师在使用标准剂量针灸治疗时引起的任何不良或有害反应。在这篇综述中,我们阐明了AE与AR之间的关系。此外,我们还整理了系统综述和荟萃分析文章中报告的针灸相关AEs。我们发现,与针灸相关的严重 AEs 非常罕见,严重 AEs 的发生率约为每 10,000 次治疗 0.04-0.08 例。最有可能发生的严重AE是气胸、中枢神经和周围神经损伤、心脏损伤、腹部器官损伤、感染和断针。常见的轻微不良反应包括针刺部位瘀伤、血肿或出血,以及血管迷走神经反应,如疲倦、头晕、昏厥或插入点残留疼痛。分析确定了导致严重不良反应的因素,包括针刺过深、穴位选择不当和针刺操作不当。分析还涉及污染针头、环境因素和皮肤消毒不充分造成的感染。此外,其他严重的 AEs(如断针)大多是由于操作不当和反复加热造成的。重要的是,大多数与针灸相关的 AE 都是可以预防的。为避免这些不良反应,针灸师在临床实践中应谨慎选择针刺部位,了解针灸的注意事项和禁忌,保持安全的针刺深度和卫生,并严格遵守标准操作程序。
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引用次数: 0
Traditional Chinese Medicine: A Promising Treatment Option for Intestinal Fibrosis. 中医药:中药:治疗肠纤维化的有效方法。
Pub Date : 2024-01-01 Epub Date: 2024-11-25 DOI: 10.1142/S0192415X24500812
Meng'en Zhou, Yan Chen, Wenqi Jin, Peng Li, Jie Hu, Xiutian Guo

Intestinal fibrosis, a common complication of inflammatory bowel disease, in particular in Crohn's disease, arises from chronic inflammation, leading to intestinal narrowing, structural damage, and functional impairment that significantly impact patients' quality of life. Current treatment options for intestinal fibrosis are limited, with surgery being the primary intervention. Traditional Chinese Medicine (TCM) has emerged as a promising approach in preventing and treating intestinal fibrosis. However, there is a scarcity of literature summarizing the mechanisms underlying TCM's efficacy in this context. To address this gap, we conducted a comprehensive review, uncovering multiple mechanisms through which TCM mitigates intestinal fibrosis. These mechanisms include immune cell balance regulation, suppression of inflammatory responses, reduction of inflammatory mediators, alleviation of colon tissue damage, restoration of intestinal function, modulation of growth factors to inhibit fibroblast activation, dynamic regulation of TIMPs and MMPs to reduce extracellular matrix deposition, inhibition of epithelial-mesenchymal transition and endothelial-mesenchymal transition, autophagy modulation, maintenance of the intestinal mucosal barrier, prevention of tissue damage by harmful factors, and regulation of cell proliferation and apoptosis. This study aims to bridge existing knowledge gaps by presenting recent evidence supporting the utilization of TCM in both clinical and experimental research settings.

肠纤维化是炎症性肠病(尤其是克罗恩病)的常见并发症,由慢性炎症引起,导致肠道狭窄、结构损伤和功能障碍,严重影响患者的生活质量。目前治疗肠纤维化的方法有限,手术是主要的干预手段。中医药已成为预防和治疗肠纤维化的一种很有前景的方法。然而,总结中医药在这方面疗效机制的文献却很少。为了填补这一空白,我们进行了全面综述,发现了中医药缓解肠纤维化的多种机制。这些机制包括调节免疫细胞平衡、抑制炎症反应、减少炎症介质、减轻结肠组织损伤、恢复肠道功能、调节生长因子以抑制成纤维细胞活化、动态调节 TIMPs 和 MMPs 以减少细胞外基质沉积、抑制上皮-间充质转化和内皮-间充质转化、自噬调节、维护肠粘膜屏障、防止有害因素对组织的损伤以及调节细胞增殖和凋亡。本研究旨在通过介绍支持在临床和实验研究环境中使用中药的最新证据,弥补现有的知识差距。
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引用次数: 0
Osthole, a Coumarin from Cnidium monnieri: A Review on Its Pharmacology, Pharmacokinetics, Safety, and Innovative Drug Delivery Platforms. 从蛇床子中提取的香豆素 Osthole:药理学、药代动力学、安全性和创新给药平台综述。
Pub Date : 2024-01-01 DOI: 10.1142/S0192415X24500678
Hao Lin, Qiang You, Xing Wei, Zongjun Chen, Xianwei Wang

Osthole, a coumarin compound mainly derived from Cnidium monnieri (L.), has attracted much interest from the scientific community owing to its multiple therapeutic properties. However, its pharmacological mechanism, pharmacokinetics, and toxicological effects are far from clear. Furthermore, the potential drug delivery platforms of osthole remain to be comprehensively delineated. The present review aimed to systematically summarize the most up-to-date information related to pharmacology, pharmacokinetics, and safety issues related to osthole, and discuss the investigations of novel drug delivery platforms. The information herein discussed was retrieved from authoritative databases, including PubMed, Web of Science, Google Scholar, Chinese National Knowledge Infrastructure (CNKI) and so on, reviewing information published up until February of 2024. New evidence shows that osthole induces a sequence of therapeutic actions and has a moderate absorption rate and rapid metabolic characteristics. In addition, this phytoconstituent possesses potential hepatotoxicity, and caution should be exercised against the risk of the drug combination. Furthermore, given its needy solubility in aqueous medium and non-organizational targeting, novel drug delivery methods have been designed to overcome these shortcomings. Given the properties of osthole, its therapeutic benefits ought to be elucidated in a greater array of comprehensive research studies, and the molecular mechanisms underlying these benefits should be explored.

Osthole 是一种香豆素化合物,主要提取自 Cnidium monnieri(L.),因其具有多种治疗特性而备受科学界关注。然而,它的药理机制、药代动力学和毒理效应还很不清楚。此外,奥司孔的潜在给药平台仍有待全面界定。本综述旨在系统总结与奥司孔相关的药理学、药代动力学和安全性问题的最新信息,并讨论新型给药平台的研究。本文讨论的信息来自权威数据库,包括PubMed、Web of Science、Google Scholar、中国国家知识基础设施(CNKI)等,查阅了截至2024年2月发表的信息。新证据表明,奥司孔可诱导一系列治疗作用,并具有吸收率适中、代谢迅速的特点。此外,这种植物成分还具有潜在的肝毒性,因此应谨慎对待联合用药的风险。此外,鉴于其在水介质中的溶解度较低,且不具有组织靶向性,人们设计了新型给药方法来克服这些缺点。鉴于奥司孔的特性,应在更多的综合研究中阐明其治疗功效,并探索这些功效的分子机制。
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引用次数: 0
Astragalus membranaceus Polysaccharide Regulates Small Intestinal Microbes and Activates IL-22 Signal Pathway to Promote Intestinal Stem Cell Regeneration in Aging Mice. 黄芪多糖调节小肠微生物并激活IL-22信号通路,促进衰老小鼠肠干细胞再生
Pub Date : 2024-01-01 Epub Date: 2024-03-26 DOI: 10.1142/S0192415X24500228
Jia-Ting Yin, Ming-Ruo Zhang, Shu Zhang, Shu-Hui Yang, Jian-Ping Li, Yun Liu, Jin-Ao Duan, Jian-Ming Guo

Aging can cause degenerative changes in multiple tissues and organs. Gastrointestinal diseases and dysfunctions are common in the elderly population. In this study, we investigated the effects of Astragalus membranaceus polysaccharide (APS) and Astragalus membranaceus ethanol extract (AEE) on age-related intestinal dysfunction and gut microbiota dysbiosis in naturally aging mice. The energy expenditure and physical activity of 23-month-old C57BL6/J mice were recorded using a metabolic cage system. Pathological changes in the intestine were evaluated using Alcian blue staining. The protein levels of leucine-rich repeats containing G protein-coupled receptor 5 (Lgr5) and Stat3 in the small intestine were determined using immunohistochemistry. The intestinal cell migration distance was assessed using bromodeoxyuridine (BrdU) immunofluorescence staining. The gene transcription levels of intestinal stem cell (ISC) markers and ISC-related signaling pathways were detected using quantitative real-time PCR (qRT-PCR). Microbiota analysis based on 16S rDNA was performed to evaluate the composition of the gut microbiota. APS and AEE improved a series of aging phenotypes in female but not in male aging mice. APS and AEE ameliorate intestinal dysfunction and histopathological changes in aging mice. APS had a more significant anti-aging effect than AEE, particularly on intestinal dysfunction. APS promotes ISC regeneration by activating the IL-22 signaling pathway. Cohousing (CH) experiments further confirmed that APS induced the IL-22 signaling pathway by increasing the abundance of Lactobacillus, thereby promoting the regeneration of ISCs. Our results show that APS may serve as a promising agent for improving age-related intestinal dysfunction.

衰老会导致多种组织和器官发生退行性变化。胃肠道疾病和功能障碍在老年人群中很常见。本研究探讨了黄芪多糖(APS)和黄芪乙醇提取物(AEE)对自然衰老小鼠与年龄相关的肠道功能障碍和肠道微生物菌群失调的影响。使用代谢笼系统记录了23月龄C57BL6/J小鼠的能量消耗和体力活动。用阿尔新蓝染色法评估了小鼠肠道的病理变化。用免疫组化法测定小肠中富含亮氨酸重复序列的G蛋白偶联受体5(Lgr5)和Stat3的蛋白水平。使用溴脱氧尿苷(BrdU)免疫荧光染色法评估肠细胞迁移距离。使用定量实时 PCR(qRT-PCR)检测肠干细胞(ISC)标记物和 ISC 相关信号通路的基因转录水平。根据 16S rDNA 进行了微生物群分析,以评估肠道微生物群的组成。APS和AEE改善了雌性衰老小鼠的一系列衰老表型,但没有改善雄性衰老小鼠的表型。APS和AEE能改善衰老小鼠的肠道功能障碍和组织病理学变化。APS的抗衰老效果比AEE更明显,尤其是在肠道功能障碍方面。APS通过激活IL-22信号通路促进ISC再生。同室(CH)实验进一步证实,APS通过增加乳酸杆菌的丰度来诱导IL-22信号通路,从而促进ISC的再生。我们的研究结果表明,APS可作为一种有希望改善与年龄有关的肠道功能障碍的药物。
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引用次数: 0
Cucurbitacin B Inhibits the Malignancy of Esophageal Carcinoma through the KIF20A/JAK/STAT3 Signaling Pathway. 葫芦素 B 通过 KIF20A/JAK/STAT3 信号通路抑制食管癌的恶性发展
Pub Date : 2024-01-01 Epub Date: 2024-01-30 DOI: 10.1142/S0192415X24500125
Chao Liu, Jian Ji, Chenglin Li

This study intends to explore the effects of Cucurbitacin B (CuB) and KIF20A on esophageal carcinoma (ESCA). Data were downloaded from the Cancer Genome Atlas (TCGA) database. The expression properties of KIF20A have been confirmed by GEPIA and ualcan from TCGA. The expression of KIF20A was determined using western blotting in ECA109 and KYSE150 cells after transfection with KIF20A, KIF20A siRNA, or numerical control siRNA (si-NC). Then, different concentrations of CuB were used to treat ECA109 and KYSE150 cells. CCK-8 and colony formation assays were used to measure cell viability, and a Transwell assay was utilized to assess cell migration and invasion ability. N-cadherin, E-cadherin, snail, p-Janus kinase 2 (JAK2), JAK2, p-signal transducer and activator of transcription 3 (STAT3), and STAT3 expression levels were evaluated using western blot. KIF20A was higher expressed in ESCA than in normal cells, and its overexpression was associated with squamous cell carcinoma, TNM stage, and lymph nodal metastasis of ESCA patients. In ECA109 and KYSE150 cells, increased KIF20A facilitated cell proliferation, migration, and invasion, whereas the knockdown of KIF20A can reverse these effects with N-cadherin. Snail expression diminished and E-cadherin increased. Similarly, CuB treatment could inhibit cell proliferation, migration, and invasion concentration dependently. Furthermore, KIF20A accelerated the expression of p-JAK2 and p-STAT3, while the application of CuB inhibited KIF20A expression and attenuated the activation of the JAK/STAT3 pathway. These findings revealed that CuB could inhibit the growth, migration, and invasion of ESCA through downregulating the KIF20A/JAK/STAT3 signaling pathway, and CuB could serve as an essential medicine for therapeutic intervention.

本研究旨在探讨葫芦素B(CuB)和KIF20A对食管癌(ESCA)的影响。数据下载自癌症基因组图谱(TCGA)数据库。KIF20A 的表达特性已由 TCGA 的 GEPIA 和 ualcan 证实。在转染 KIF20A、KIF20A siRNA 或数值对照 siRNA(si-NC)后的 ECA109 和 KYSE150 细胞中,用 Western 印迹法测定 KIF20A 的表达。然后用不同浓度的 CuB 处理 ECA109 和 KYSE150 细胞。CCK-8和集落形成试验用于测定细胞活力,Transwell试验用于评估细胞迁移和侵袭能力。用 Western 印迹法评估了 N-cadherin、E-cadherin、蜗牛、p-Janus 激酶 2(JAK2)、JAK2、p-信号转导和激活转录 3(STAT3)以及 STAT3 的表达水平。KIF20A在ESCA中的表达高于正常细胞,其过表达与ESCA患者的鳞状细胞癌、TNM分期和淋巴结转移有关。在 ECA109 和 KYSE150 细胞中,KIF20A 的增加促进了细胞的增殖、迁移和侵袭,而 KIF20A 的敲除可与 N-cadherin一起逆转这些效应。蜗牛表达减少,E-cadherin 增加。同样,CuB 处理可抑制细胞增殖、迁移和侵袭的浓度依赖性。此外,KIF20A 可加速 p-JAK2 和 p-STAT3 的表达,而 CuB 可抑制 KIF20A 的表达并减轻 JAK/STAT3 通路的激活。这些研究结果表明,CuB可通过下调KIF20A/JAK/STAT3信号通路抑制ESCA的生长、迁移和侵袭,CuB可作为一种重要的治疗干预药物。
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引用次数: 0
Using Quercetin to Construct Molecularly Imprinting Polymer in the Preparation and Enrichment of Flavonol and Flavonoid Compounds. 利用槲皮素构建分子印迹聚合物以制备和富集黄酮醇和黄酮类化合物
Pub Date : 2024-01-01 Epub Date: 2024-06-14 DOI: 10.1142/S0192415X24500459
Dan-Dan Yang, Shu-Yi Li, Xiao-Wei Xu, Qing-Yao Li, Jia-Yuan He, Lian-Di Zhou, Qi-Hui Zhang

Flavonol and flavonoid compounds are important natural compounds with various biomedical activities. Therefore, it is of great significance to develop a strategy for the specific extraction of flavonol and flavonoid compounds. Quercetin is a well-studied flavonoid possessing many health benefits. This compound is a versatile antioxidant known to possess protective abilities against body tissue injury induced by pathological situations and various drug toxicities. Although quercetin is widely distributed in many plants, its content generally is not very high. Therefore, the specific extraction of quercetin as well as other flavonol and flavonoid compounds has profound significance. In this work, the quercetin molecularly imprinting polymer (QMIP) was successfully prepared, in which a typical flavonol quercetin was selected as the template molecule. QMIP was synthesized by performing the surface molecular imprinting technology on the surface of NH2-MIL-101(Fe). Our study results showed that QMIP exhibited quick binding kinetic behavior, a high adsorption capacity (57.04[Formula: see text]mg/g), and the specific recognition ability toward quercetin compared with structurally distinct compounds (selective [Formula: see text]). The specific adsorption ability of quercetin by QMIP was further explained using computation simulation that molecules with non-planar 3D conformations hardly entered the molecularly imprinted cavities on QMIP. Finally, QMIP was successfully used for the specific extraction of quercetin and five other flavonol and flavonoid compounds in the crude extracts from Sapium sebiferum. This study proposes a new strategy to synthesize the molecularly imprinted polymer based on a single template for enriching and loading a certain class of active ingredients with similar core structures from variable botanicals.

黄酮醇和类黄酮化合物是重要的天然化合物,具有多种生物医学活性。因此,开发一种特定提取黄酮醇和类黄酮化合物的策略具有重要意义。槲皮素是一种经过充分研究的黄酮类化合物,具有多种健康益处。这种化合物是一种多功能抗氧化剂,对病理情况和各种药物毒性引起的身体组织损伤具有保护能力。虽然槲皮素广泛分布于许多植物中,但其含量一般并不高。因此,对槲皮素以及其他黄酮醇和黄酮类化合物进行特定提取具有重要意义。本研究以典型的黄酮醇槲皮素为模板分子,成功制备了槲皮素分子印迹聚合物(QMIP)。通过在 NH2-MIL-101(Fe)表面进行表面分子印迹技术合成了 QMIP。研究结果表明,与结构不同的化合物相比,QMIP 具有快速的结合动力学行为、较高的吸附容量(57.04[式:见正文]mg/g)和对槲皮素的特异性识别能力(选择性[式:见正文])。计算模拟进一步解释了 QMIP 对槲皮素的特异性吸附能力,即非平面三维构象的分子很难进入 QMIP 上的分子印迹空腔。最后,QMIP 被成功地用于特异性提取乌桕粗提物中的槲皮素及其他五种黄酮醇和黄酮类化合物。本研究提出了一种基于单一模板合成分子印迹聚合物的新策略,用于从不同植物中富集和负载具有相似核心结构的某类活性成分。
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引用次数: 0
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The American journal of Chinese medicine
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