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Zuogui Pills Improve the Learning and Memory Ability of Brain-Aging Mice through the Estrogen Receptor ERα Methylation Pathway. 左归丸通过雌激素受体ERα甲基化途径改善脑衰老小鼠的学习和记忆能力
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-09-03 DOI: 10.2174/0113862073306093240820113714
Yang Huang, Lili Zhong, Jing Yang, Qiaomei Dai, Li Zhao, Mengdi Zhang, Hong Liu

Introduction: Sex hormones are important factors in maintaining brain function and acting as brain protectors. Recent research suggests that neuronal damage in brain aging may be linked to the methylation of the estrogen receptor α (ERα). However, the mechanism of Zuogui Pills (ZGW) in brain-aging ERα DNA methylation and neuronal repair remains unknown.

Materials and methods: D-galactose-induced ovary removal mice were used as a model of aging. Changes in estrous cycle were detected in mice by vaginal cell smear. Animal behavior tests, including the Morris water maze (MWM) and new object recognition (NOR) test, were conducted. Hematoxylin-eosin (HE) and Nissl-staining were carried out to assess hippocampal neurogenesis. Enzyme-linked immunosorbent assay (ELISA) was performed for 5- methylcytosine methylation levels, and immunohistochemistry (IHC) and western blotting (WB) experiments were performed to assess ERα/DNA methyltransferase 1 (DNMT1) expression after ZGW treatment. Finally, bisulfite sequencing PCR (BSP) analysis was performed to identify methylated differentially expressed estrogen receptor 1 (ESR1) gene in D-gal-induced senescent neurons before and after ZGW treatment.

Results: We found that ERα methylation was involved in the delayed brain ageing process of ZGW. Mechanistically, ZGW can improve the learning and memory ability of brain-aging mice, reduce the expression of 5-methylcytosine (5-mc) in serum, increase the amount of ERα, inhibit the expression of DNMT1, and significantly reduce methylated expression of the ESRI gene.

Conclusion: Our data suggested that ZGW slowed down D-gal-induced brain aging in mice, and these results showed that ZGW is beneficial for aging. It may be used for neuronal protection in aging.

引言性激素是维持大脑功能和保护大脑的重要因素。最新研究表明,脑衰老过程中神经元的损伤可能与雌激素受体α(ERα)的甲基化有关。然而,左归丸(ZGW)在脑衰老ERα DNA甲基化和神经元修复中的作用机制仍然未知:材料和方法:采用D-半乳糖诱导的卵巢切除小鼠作为衰老模型。通过阴道细胞涂片检测小鼠发情周期的变化。进行动物行为测试,包括莫里斯水迷宫(MWM)和新物体识别(NOR)测试。采用苏木精-伊红(HE)和Nissl染色法评估海马神经发生。酶联免疫吸附试验(ELISA)检测了5-甲基胞嘧啶甲基化水平,免疫组化(IHC)和免疫印迹(WB)实验评估了ZGW处理后ERα/DNA甲基转移酶1(DNMT1)的表达。最后,进行了亚硫酸氢盐测序PCR(BSP)分析,以确定ZGW处理前后D-gal诱导的衰老神经元中甲基化差异表达的雌激素受体1(ESR1)基因:结果:我们发现ERα甲基化参与了ZGW延缓脑衰老的过程。从机理上讲,ZGW能改善脑衰老小鼠的学习记忆能力,降低血清中5-甲基胞嘧啶(5-mc)的表达,增加ERα的含量,抑制DNMT1的表达,并显著降低ESRI基因的甲基化表达:我们的数据表明,ZGW 可延缓 D-gal 诱导的小鼠脑衰老。这些结果表明,ZGW 对衰老有益,可用于衰老过程中的神经元保护。
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引用次数: 0
In Silico Molecular Docking and Molecular Dynamics Analysis of Antimicrobial Triazole Derivatives: Insights from Synthesis, Computational and In Vitro Studies. 抗菌三唑衍生物的分子对接和分子动力学分析:合成、计算和体外研究的启示。
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-08-28 DOI: 10.2174/0113862073314430240730095615
Shikha Sharma, Naveen Kumawat, Suraj N Mali, Monika Meghani, Nitin Kumar, Bijo Mathew, Sunil Kumar

Introduction: In the ongoing fight against bacterial resistance to antibiotics, this study focuses on synthesizing and evaluating 1,2,4-triazole derivatives to explore their potential as new antibacterial agents. 1,2,4-Triazole compounds are promising drug candidates with a wide range of therapeutic effects, including pain relief, antiseptic, antimicrobial, antioxidant, antiurease, anti-inflammatory, diuretic, anticancer, anticonvulsant, antidiabetic, and antimigraine properties.

Method: The structures of all the synthesized compounds were identified using their physicochemical properties and spectral techniques, such as IR and NMR. These compounds were then evaluated in molecular docking studies against antimicrobial activity in vitro and further supported by molecular dynamics studies.

Result: Compound 7, featuring a 6-chloro group on the phenyl ring, emerged as the most effective against Gram-positive S. aureus compared to the standard antibiotic ciprofloxacin. Docking studies revealed high and comparable affinities for all ten ligands, with compounds 4 and 6 showing the best-docked activity against Penicillin Acylase mutants. Further, compounds 6 and 10 displayed significant affinity against D-alanine-D-alanine ligase (DDL) from Yersinia pestis during 100 ns MD simulation.

Conclusion: Notably, compound 7 demonstrated the highest binding score to the 5C1P protein, suggesting its potential as a lead molecule for the development of potent and safer antimicrobial agents. This research contributes valuable insights into addressing the escalating challenge of bacterial resistance.

简介:为了对抗细菌对抗生素的耐药性,本研究重点合成并评估了 1,2,4-三唑衍生物,以探索其作为新型抗菌剂的潜力。1,2,4-三唑化合物是很有前途的候选药物,具有广泛的治疗作用,包括止痛、防腐、抗菌、抗氧化、抗尿素酶、抗炎、利尿、抗癌、抗惊厥、抗糖尿病和抗偏头痛等特性:方法:利用理化性质和光谱技术(如红外光谱和核磁共振)确定所有合成化合物的结构。然后在分子对接研究中对这些化合物的体外抗菌活性进行了评估,并通过分子动力学研究进一步证实了这些化合物的抗菌活性:结果:与标准抗生素环丙沙星相比,苯环上带有 6 个氯基的化合物 7 对革兰氏阳性金黄色葡萄球菌最有效。对接研究显示,所有十种配体都具有很高的亲和力,其中化合物 4 和 6 对青霉素酰化酶突变体的对接活性最好。此外,在 100 ns MD 模拟过程中,化合物 6 和 10 对鼠疫耶尔森菌的 D-丙氨酸-D-丙氨酸连接酶(DDL)具有显著的亲和力:值得注意的是,化合物 7 与 5C1P 蛋白的结合得分最高,这表明它有可能成为开发强效、更安全的抗菌剂的先导分子。这项研究为应对不断升级的细菌耐药性挑战提供了宝贵的见解。
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引用次数: 0
A Novel Cuproptosis-Related Gene Signature Predicts Prognosis in Papillary Thyroid Carcinoma Patients 新型杯突相关基因特征可预测甲状腺乳头状癌患者的预后
IF 1.8 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-08-28 DOI: 10.2174/0113862073333880240819105537
Jun Cao, Shijia Zhang, Kehui Zhou, Xiaochun Mao, Ming Zhao, Jinbiao Shang, Xiabin Lan
background: Cuproptosis is a novel type of cell death mediated by protein lipoylation,and is closely related to mitochondrial metabolism. Clinical association of cuproptosis-related genes(CRGs)in thyroid cancer, however, remains unclear. In this study, we systematically evaluated the differential expression and genetic alterations of CRGs in papillary thyroid cancer (PTC) and constructed a CRG signature to predict the prognosis of PTC patients. method: We integrated the data of The Cancer Genome Atlas (TCGA) database and analyzed the expression of 10 CRGs in PTC. CRG signature was constructed by univariate Cox analysis and selection operator (LASSO) Cox regression. In addition, the signature-related molecular features were validated by a combination of functional enrichment, Cox regression, and immune infiltration analysis. Independent validation cohort data and quantitative real-time polymerase chain reaction (qRT-PCR) were used to validate the expression of differentially expressed CRG (CDKN2A). result: Thyroid cancer patients could be divided into two subtypes (low and high CRG score groups) and we found that overall survival (OS) of patients was lower in high CRG score group (HCSG) than in low CRG score group (LCSG) (p &amp;amp;lt; 0.001). And the area under the curve (AUC) values for 3 years, 5 years, and 8 years were 0.872, 0.941, and 0.976, respectively. Cox regression analysis showed that the CRG score could be used as an independent prognostic indicator for PTC. Functional enrichment analysis indicated that the CRG prognostic signature was also associated with the tumor immune microenvironment. In HCSG, the immune suppression type cell score is significantly higher than in LCSG. In addition, we identified the expression of CRG (CDKN2A) by qRT-PCR, and the results were consistent with the TCGA database. conclusion: Our CRG signature has a good predictive ability for the prognosis of PTC patients. CRGs may play an important role in tumorigenesis and could be used to predict immunotherapy efficacy of PTC.
背景:杯突症是一种由蛋白质脂酰化介导的新型细胞死亡,与线粒体代谢密切相关。然而,杯突相关基因(CRGs)与甲状腺癌的临床关联仍不清楚。在这项研究中,我们系统评估了CRGs在甲状腺乳头状癌(PTC)中的差异表达和基因改变,并构建了一个CRG特征来预测PTC患者的预后:我们整合了癌症基因组图谱(TCGA)数据库的数据,分析了10个CRGs在PTC中的表达。通过单变量考克斯分析和选择算子(LASSO)考克斯回归构建了CRG特征。此外,还结合功能富集、Cox 回归和免疫浸润分析验证了与特征相关的分子特征。独立验证队列数据和定量实时聚合酶链反应(qRT-PCR)用于验证差异表达的 CRG(CDKN2A)的表达:甲状腺癌患者可分为两个亚型(CRG评分低组和高组),我们发现CRG评分高组(HCSG)患者的总生存期(OS)低于CRG评分低组(LCSG)(p&;amp;amp;lt;0.001)。3年、5年和8年的曲线下面积(AUC)值分别为0.872、0.941和0.976。Cox回归分析表明,CRG评分可作为PTC的独立预后指标。功能富集分析表明,CRG预后特征还与肿瘤免疫微环境有关。在 HCSG 中,免疫抑制型细胞得分明显高于 LCSG。此外,我们还通过 qRT-PCR 鉴定了 CRG(CDKN2A)的表达,结果与 TCGA 数据库一致:我们的 CRG 特征对 PTC 患者的预后具有良好的预测能力。CRGs可能在肿瘤发生过程中扮演重要角色,可用于预测PTC的免疫治疗疗效。
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引用次数: 0
Rosmanol Alleviates Myocardial Ischemia-Reperfusion Injury by Enhancing the Myocardial miR-126/VEGF/PI3K/AKT Signaling in STZ-Induced Diabetic Rats. 玫瑰酚通过增强STZ诱导的糖尿病大鼠心肌miR-126/VEGF/PI3K/AKT信号传导缓解心肌缺血再灌注损伤
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-08-26 DOI: 10.2174/0113862073285839240808113152
Menghai Wu, Huaxin Qi, Jun Li, Periyannan Velu, Xia Han

Background: A major factor in type 1 diabetes mortality is Ischemic Heart Disease (IHD). In order to treat IHD, blood flow must be restored to the heart, which results in myocardial ischemia-reperfusion (MI/R) damage. While rosmanol inhibits MI/R damage, its role in diabetic- MI/R (D-MI/R) injury remains unclear. Both microRNA (miR) 126 and the PI3K/AKT signaling pathway have been linked to preventing MI/R damage.

Objective: The objective of the present study was to investigate whether rosmanol inhibits DMI/ R-injury in diabetic rats and whether miR-126-phosphatidylinositol 3-kinase (PI3K)/ protein kinase B axis (miR-126-PI3K/AKT) is implicated in this protective effect.

Methods: For 30 days, diabetic rats received either distilled water or the drug rosmanol (40 mg/kg, orally) before being subjected to MI/R.

Results: The findings from the current study demonstrated how rosmanol reduced MI/R damage in rats with diabetes caused by streptozotocin (STZ). Using spectrophotometry, it was possible to measure the decrease in myocardial enzyme levels, the rise in cardiac viability, the inhibition of myocardial oxidative stress, the increase in cardiac function, and the detection of these changes using a hemodynamic monitoring system. In addition, rosmanol augmented the miR- 126-PI3K/AKT in the hearts of ischemic rats. After stimulating the myocardial miR-126- PI3K/AKT axis, our results showed that rosmanol protected the heart against MI/R in STZinduced diabetic rats.

Conclusion: According to the most recent research, rosmanol may be a useful tool in the therapy of diabetic IHD since it is an effective agent against D-MI/R damage.

背景:导致 1 型糖尿病患者死亡的一个主要因素是缺血性心脏病(IHD)。为了治疗缺血性心脏病,必须恢复心脏的血流量,这会导致心肌缺血再灌注(MI/R)损伤。虽然玫瑰酚能抑制心肌缺血再灌注损伤,但它在糖尿病心肌缺血再灌注损伤(D-MI/R)中的作用仍不清楚。微RNA(miR)126和PI3K/AKT信号通路都与预防MI/R损伤有关:本研究旨在探讨玫瑰酚是否能抑制糖尿病大鼠的 DMI/R 损伤,以及 miR-126 磷脂酰肌醇 3- 激酶(PI3K)/ 蛋白激酶 B 轴(miR-126-PI3K/AKT)是否与这种保护作用有关:方法:糖尿病大鼠在接受MI/R治疗前30天,口服蒸馏水或药物罗司洛尔(40毫克/千克):结果:本研究结果表明,罗司洛尔能减轻链脲佐菌素(STZ)引起的糖尿病大鼠心肌梗死/心肌损伤。通过分光光度法,可以测量心肌酶水平的下降、心脏活力的提高、心肌氧化应激的抑制、心脏功能的增强,并利用血液动力学监测系统检测这些变化。此外,玫瑰酚还能增强缺血大鼠心脏中的 miR- 126-PI3K/AKT。我们的研究结果表明,刺激心肌miR-126- PI3K/AKT轴后,洛司司醇能保护STZ诱导的糖尿病大鼠的心脏免受心肌梗死/再损伤:结论:根据最新研究,玫瑰酚是一种有效的抗 D-MI/R 损伤的药物,因此可能是治疗糖尿病性心肌梗死的有效工具。
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引用次数: 0
WITHDRAWN: Comparative Experimental Study of using Tramadol and Nefopam in Pain Management 使用曲马多和奈福泮治疗疼痛的对比实验研究
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-08-22 DOI: 10.2174/0113862073252534231122073045
Gaber El-Saber Batiha, Hayder M Al-Kuraishy, Omnia Momtaz Al-Fakhrany, Engy Elekhnawy

The manuscript has been withdrawn upon author request.

Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.

The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php

Bentham science disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneouslysubmitted or published elsewhere. Furthermore, any data, illustration, structure, or table that has been published elsewheremust be reported, and copyright permission for reproduction must be obtained. Additionally, plagiarism is strictly forbidden,and by submitting the article for publication, the authors agree that the publishers have the legal right to take appropriate actionagainst the authors if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that thecopyright of their article is transferred to the publishers if and when the article is accepted for publication.

背景:疼痛是一种令人不安的感觉和情绪,主要由组织损伤性刺激引发。本研究旨在评估曲马多和奈福泮对急性疼痛的潜在影响:将 30 只 Sprague-Dawley 大鼠(每只 200-250 克)随机分为三组(n=10)。奈福泮组腹腔注射奈福泮(3.5 毫克/千克),曲马多组腹腔注射曲马多(50 毫克/千克),对照组用生理盐水。评估和监测大鼠疼痛的方法主要有两种:热板法和浸入尾部的弹尾法:结果表明:与对照组相比,接受曲马多和奈福泮治疗的动物疼痛有明显变化(P0.05)。此外,热板试验(手爪舔参数)和尾晕试验在曲马多治疗组和奈福泮治疗组之间也发现了相当大的差异。然而,在热板试验(跳跃参数)中,两组之间未发现明显差异(P=0.101):结论:在中度至重度疼痛的急性期,曲马多在抑制疼痛刺激方面的镇痛活性优于奈福泮,因此曲马多是短期治疗术后疼痛的首选。
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引用次数: 0
Network Pharmacology, Molecular Docking Analysis and Experiment Validations on Molecular Targets and Mechanisms of the Dispel-Scar Ointment in Scar Treatment. 关于 Dispel-Scar 软膏治疗疤痕的分子靶点和机制的网络药理学、分子对接分析和实验验证。
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-08-21 DOI: 10.2174/0113862073335953240820075044
Zhaoyi Li, Yi Cao, Hui Li, Sihua Le, Libo Yin

Ethnopharmacological relevance: Dispel-Scar Ointment is used in Traditional Chinese Medicine to treat scarred tissue and increasing evidence has shown that DSO has potent therapeutic; however, its exact mechanism remains unexplored.

Aim of the study: This study explored the molecular mechanisms of action of DSO in scarring using network pharmacology, molecular docking, and experimental validation.

Materials and methods: Public databases were used to predict the bioactive ingredients and putative targets of DSO against scars. A compounds-targets network was constructed using the Cytoscape software. Enrichment analysis was performed using ClueGo and FunRich to specify the biological functions and associated pathways of hub targets. Molecular docking was used to verify the correlation between the major active components and hub targets, visualised using PyMol 2.3. Experimental validations were conducted to elucidate the influence of DSO on keloid fibroblast cells using the CCK-8, wound-scratch, cell reactive oxygen species, and western blot assays. Results:Network pharmacological analysis of DSO for scar treatment identified 146 ingredients and 1078 gene targets. Major targets included, prostaglandin-endoperoxide synthase 2 matrix metallopeptidases, and nitric oxide synthase 2. ClueGo analysis revealed 29 pathways (p&amp;amp;lt;0.05) and FunRich 345 pathways (p&amp;amp;lt;0.05), mainly toll-like receptor, TGF-β, interleukin-4/13, glypican, and tumour necrosis factor-related apoptosis-inducing ligand pathways. Molecular docking showed MMP2-flavoxanthin, MMP9-luteolin and MMP-9-kaempferol bound best to DSO. DSO could inhibit the proliferation and migration of scar fibroblasts and promote their apoptosis in a concentration-dependent manner. DSO also decreased TGF-β1, -βR2, pSMAD2, pSMAD3, SMAD4, CoL1a1, and MMP2 expression.

Conclusions: Network pharmacology, molecular docking, and experimental validation showed DSO&amp;#039;s potential in treating scars. It may inhibit scars via the TGF-β1/SMADs/MMPs signalling pathway, providing a basis for DSO&amp;#039;s scar treatment application.

民族药理学意义:祛疤膏在中医中被用于治疗瘢痕组织,越来越多的证据表明祛疤膏具有强大的治疗作用;然而,其确切机制仍有待探索:研究目的:本研究采用网络药理学、分子对接和实验验证等方法探讨了DSO对瘢痕的分子作用机制:材料:研究人员利用公共数据库预测了DSO抗疤痕的生物活性成分和假定靶点。使用 Cytoscape 软件构建了化合物-靶点网络。利用ClueGo和FunRich进行了富集分析,以明确枢纽靶点的生物功能和相关途径。分子对接用于验证主要活性成分与中心靶标之间的相关性,并使用 PyMol 2.3 进行可视化。实验验证采用 CCK-8、伤口划痕、细胞活性氧和 Western 印迹检测法阐明了 DSO 对瘢痕疙瘩成纤维细胞的影响。结果:DSO治疗瘢痕的网络药理学分析确定了146种成分和1078个基因靶点。主要靶点包括前列腺素内过氧化物合成酶 2、基质金属肽酶和一氧化氮合成酶 2。ClueGo 分析发现了 29 个通路(p&amp;amp;lt;0.05)和 FunRich 345 个通路(p&amp;amp;lt;0.05),主要是类收费受体、TGF-β、白细胞介素-4/13、glypican 和肿瘤坏死因子相关凋亡诱导配体通路。分子对接显示,MMP2-黄酮黄素、MMP9-木犀草素和MMP-9-山奈酚与DSO结合得最好。DSO可抑制瘢痕成纤维细胞的增殖和迁移,并以浓度依赖的方式促进其凋亡。DSO 还能降低 TGF-β1、-βR2、pSMAD2、pSMAD3、SMAD4、CoL1a1 和 MMP2 的表达:网络药理学、分子对接和实验验证表明,DSO&amp;#039;具有治疗疤痕的潜力。它可能通过 TGF-β1/SMADs/MMPs 信号通路抑制疤痕,为 DSO&amp;#039 的疤痕治疗应用提供了依据。
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引用次数: 0
Exploring the Bioactive Potential of Exotic Fruits from Sri Lanka: A Treasure Trove of Medicinal Properties. 探索斯里兰卡外来水果的生物活性潜力:药用价值的宝库。
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-08-19 DOI: 10.2174/0113862073304276240606102447
D M Danuri Savindi Dissanayake, I G Sahasra Heshani, Sadhana Hassan, Anchala I Kuruppu

Tropical fruits are often studied to determine their content of bioactive compounds that contain health-enhancing properties and are often identified to hold a rich nutritional composition. Their bioactive compounds are classified through their phenolic, flavonoid, and antioxidant properties, while some tropical fruits are known to have other properties such as anticancer and anti-inflammatory activity. Sri Lanka is an island with abundant resources. One such resource is exotic fruits. Exotic fruits are known as edible fruits, which are not necessarily native but consist of a unique flavor profile, fragrance, shape, or appearance. Exotic fruits are usually consumed on their own or consumed as beverages, pickles, jams, salads, and desserts. The market-friendly tropical fruits in Sri Lanka include a vast number, and some of them are mango, Ceylon olives, durian, jackfruit, rambutan, soursop, passion fruit, and star fruit. These fruits contribute to the rice culinary heritage of Sri Lanka, and most of them are exported worldwide. At present, the traditional medicine system is quite popular among the public due to its less toxic nature and easy access. This review is aimed at evaluating the antioxidant, cytotoxic, anticancer, and anti-inflammatory properties of eight selected exotic fruits mentioned above and their traditional usage, which is based on the literature of various scientific studies conducted on these tropical fruits.

人们经常研究热带水果,以确定其生物活性化合物的含量,这些化合物具有增进健康的特性,而且经常被认定含有丰富的营养成分。热带水果的生物活性化合物可根据其酚类、类黄酮和抗氧化特性进行分类,有些热带水果还具有其他特性,如抗癌和抗炎活性。斯里兰卡是一个资源丰富的岛屿。其中一种资源就是奇特水果。异国水果被称为可食用水果,不一定是本地水果,但具有独特的风味、香味、形状或外观。外来水果通常单独食用或作为饮料、腌菜、果酱、沙拉和甜点食用。斯里兰卡市场上的热带水果种类繁多,其中包括芒果、锡兰橄榄、榴莲、菠萝蜜、红毛丹、酸果、百香果和杨桃。这些水果为斯里兰卡的稻米烹饪遗产做出了贡献,其中大部分出口到世界各地。目前,传统医药系统因其毒性较低、易于获取而颇受公众欢迎。本综述旨在评估上述八种精选外来水果的抗氧化、细胞毒性、抗癌和消炎特性及其传统用法,其依据是对这些热带水果进行的各种科学研究文献。
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引用次数: 0
Correlation between Chemical Fertilization Practices, Phytochemical Response, and Biological Activities of Cannabis sativa L. 大麻化学施肥方法、植物化学反应和生物活性之间的相关性
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-08-13 DOI: 10.2174/0113862073319590240801112332
Marianela Simonutti, Gisela Seimandi, Geraldina Richard, Juan Marcelo Zabala, Marcos Derita

The plant kingdom offers a wealth of molecules with potential efficacy against various human, animal, and plant crop infections and illnesses. Cannabis sativa L. has garnered significant attention in recent decades within the scientific community due to its broad biological activity. Key bioactive compounds such as cannabinoids and phenolic compounds have been isolated from this plant, driving its bioactivity. Numerous studies have highlighted the impact of different agronomic practices, particularly fertilization, on the phytochemical composition, notably altering the percentage of various chemical groups. This review aims to present updated fertilization recommendations, crop requirements, and their implications for the chemical composition of C. sativa plants, along with major biological properties documented in the literature over the past five years. Various databases were utilized to summarize information on fertilization and crop requirements, chemical composition, bioassays employed, natural products (extracts or isolated compounds), and bioactivity results. Through this review, it is evident that C. sativa holds promise as a source of novel molecules for treating diverse human diseases. Nonetheless, careful consideration of agronomic practices is essential to optimize chemical composition and maximize therapeutic potential.

植物王国提供了大量对人类、动物和植物作物的各种感染和疾病具有潜在疗效的分子。由于大麻具有广泛的生物活性,近几十年来它在科学界引起了极大的关注。从这种植物中分离出了大麻素和酚类化合物等关键生物活性化合物,推动了其生物活性的发展。许多研究都强调了不同农艺方法(尤其是施肥)对植物化学成分的影响,特别是改变了各种化学组的百分比。本综述旨在介绍最新的施肥建议、作物要求及其对荠菜植物化学成分的影响,以及过去五年文献中记载的主要生物特性。我们利用各种数据库总结了有关施肥和作物要求、化学成分、采用的生物测定、天然产品(提取物或分离化合物)以及生物活性结果的信息。通过这篇综述,可以看出荠菜有望成为治疗各种人类疾病的新型分子来源。然而,要优化化学成分并最大限度地发挥治疗潜力,必须仔细考虑农艺实践。
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引用次数: 0
ITGB3 is a Novel Prognostic Biomarker and Correlates with Aberrant Methylation and Tumor Immunity in Clear Cell Renal Cell Carcinoma. ITGB3 是一种新型预后生物标记物,与透明细胞肾细胞癌的甲基化异常和肿瘤免疫相关。
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-08-12 DOI: 10.2174/0113862073311689240730112355
Hao-Yun Luo, Jun-Ming Feng, Jun Luo, Tian Tian

Background: Current evidence highlights clear cell renal carcinoma (ccRCC) as the most prevalent form of kidney cancer despite ongoing challenges in treating advanced-stage disease. Integrin subunit beta 3 (ITGB3) has recently emerged as a critical player in tumorigenesis, prompting our investigation into its role in ccRCC. This study aimed to elucidate the mechanisms responsible for ITGB3 downregulation and evaluate its clinical significance, particularly regarding its impact on the immune landscape within ccRCC.

Methods: We first conducted analyses utilizing data from both TCGA and GEO datasets to explore ITGB3 expression in ccRCC tissues. Subsequently, we evaluated the association between ITGB3 expression levels and patient prognosis and pathological staging. Pathway and functional enrichment analyses were performed to assess correlations between ITGB3 and immune and methylation-related pathways. Additionally, we examined the relationship between ITGB3 transcriptional expression and DNA hypermethylation. A prognostic risk model was developed using LASSO-based analysis on selected ITGB3-associated DNA methylation probes. Immunohistochemistry (IHC) analysis, alongside TIMER and ssGSEA results, was utilized to investigate ITGB3 expression and its association with immune cell infiltration.

Results: Our analyses revealed significant downregulation of ITGB3 mRNA expression in ccRCC tissues compared to other members of the ITGB family, consistent across TCGA and GEO datasets. Higher ITGB3 expression correlated with improved prognosis and lower pathological stage in ccRCC patients. Pathway and functional enrichment analyses demonstrated positive correlations between ITGB3 and immune and methylation-related pathways, while ITGB3 transcriptional expression showed a negative correlation with DNA hypermethylation. The established prognostic risk model identified a high-risk group with poorer survival probabilities than the low-risk group. Immunohistochemical quantification revealed a positive correlation between CD4+ and CD8+ immune cell infiltration and ITGB3 expression.

Conclusion: Overall, our study provides compelling evidence supporting the significant role of ITGB3 in ccRCC immunity. The downregulation of ITGB3, coupled with its association with better prognosis and immune activation, suggests its potential as a therapeutic target and prognostic marker for this patient population.

背景:尽管晚期肾癌的治疗仍面临挑战,但目前的证据表明透明细胞肾癌(ccRCC)是最常见的肾癌形式。Integrin subunit beta 3(ITGB3)最近被认为是肿瘤发生过程中的一个关键角色,这促使我们研究它在ccRCC中的作用。本研究旨在阐明ITGB3下调的机制,并评估其临床意义,尤其是对ccRCC内免疫环境的影响:我们首先利用TCGA和GEO数据集的数据进行分析,探讨ITGB3在ccRCC组织中的表达。随后,我们评估了 ITGB3 表达水平与患者预后和病理分期之间的关联。我们进行了通路和功能富集分析,以评估 ITGB3 与免疫和甲基化相关通路之间的相关性。此外,我们还研究了ITGB3转录表达与DNA高甲基化之间的关系。通过对选定的 ITGB3 相关 DNA 甲基化探针进行基于 LASSO 的分析,我们建立了一个预后风险模型。免疫组化(IHC)分析与TIMER和ssGSEA结果一起用于研究ITGB3的表达及其与免疫细胞浸润的关系:我们的分析表明,与ITGB家族的其他成员相比,ITGB3 mRNA在ccRCC组织中的表达明显下调,这在TCGA和GEO数据集中是一致的。ITGB3的高表达与ccRCC患者预后的改善和病理分期的降低相关。通路和功能富集分析表明,ITGB3与免疫和甲基化相关通路呈正相关,而ITGB3转录表达与DNA高甲基化呈负相关。已建立的预后风险模型发现,高风险组的生存概率低于低风险组。免疫组化定量分析显示,CD4+和CD8+免疫细胞浸润与ITGB3表达呈正相关:总之,我们的研究提供了令人信服的证据,支持 ITGB3 在 ccRCC 免疫中的重要作用。ITGB3的下调及其与较好预后和免疫激活的相关性表明,ITGB3有可能成为这一患者群体的治疗靶点和预后标志物。
{"title":"ITGB3 is a Novel Prognostic Biomarker and Correlates with Aberrant Methylation and Tumor Immunity in Clear Cell Renal Cell Carcinoma.","authors":"Hao-Yun Luo, Jun-Ming Feng, Jun Luo, Tian Tian","doi":"10.2174/0113862073311689240730112355","DOIUrl":"https://doi.org/10.2174/0113862073311689240730112355","url":null,"abstract":"<p><strong>Background: </strong>Current evidence highlights clear cell renal carcinoma (ccRCC) as the most prevalent form of kidney cancer despite ongoing challenges in treating advanced-stage disease. Integrin subunit beta 3 (ITGB3) has recently emerged as a critical player in tumorigenesis, prompting our investigation into its role in ccRCC. This study aimed to elucidate the mechanisms responsible for ITGB3 downregulation and evaluate its clinical significance, particularly regarding its impact on the immune landscape within ccRCC.</p><p><strong>Methods: </strong>We first conducted analyses utilizing data from both TCGA and GEO datasets to explore ITGB3 expression in ccRCC tissues. Subsequently, we evaluated the association between ITGB3 expression levels and patient prognosis and pathological staging. Pathway and functional enrichment analyses were performed to assess correlations between ITGB3 and immune and methylation-related pathways. Additionally, we examined the relationship between ITGB3 transcriptional expression and DNA hypermethylation. A prognostic risk model was developed using LASSO-based analysis on selected ITGB3-associated DNA methylation probes. Immunohistochemistry (IHC) analysis, alongside TIMER and ssGSEA results, was utilized to investigate ITGB3 expression and its association with immune cell infiltration.</p><p><strong>Results: </strong>Our analyses revealed significant downregulation of ITGB3 mRNA expression in ccRCC tissues compared to other members of the ITGB family, consistent across TCGA and GEO datasets. Higher ITGB3 expression correlated with improved prognosis and lower pathological stage in ccRCC patients. Pathway and functional enrichment analyses demonstrated positive correlations between ITGB3 and immune and methylation-related pathways, while ITGB3 transcriptional expression showed a negative correlation with DNA hypermethylation. The established prognostic risk model identified a high-risk group with poorer survival probabilities than the low-risk group. Immunohistochemical quantification revealed a positive correlation between CD4+ and CD8+ immune cell infiltration and ITGB3 expression.</p><p><strong>Conclusion: </strong>Overall, our study provides compelling evidence supporting the significant role of ITGB3 in ccRCC immunity. The downregulation of ITGB3, coupled with its association with better prognosis and immune activation, suggests its potential as a therapeutic target and prognostic marker for this patient population.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970788","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
Electroacupuncture Ameliorates Knee Osteoarthritis By Rebalancing T Cell Homeostasis as Revealed By Immune Repertoire (IR) Sequencing. 电针通过重新平衡T细胞平衡改善膝骨关节炎--免疫汇聚(IR)测序揭示了这一点
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-08-12 DOI: 10.2174/0113862073303471240805061026
Wenrui Jia, Yunan Zhang, Tianqi Wang, Cunzhi Liu, Jianfeng Tu, Guangxia Shi, LingYi Cai, Jingwen Yang, Guangrui Huang

Background: In this study, we used immune repertoire (IR) sequencing technology to profile the diversity of peripheral blood T cell receptors and used transcriptomics to profile the gene expression of peripheral blood neutrophil mRNA in patients with mild-moderate knee osteoarthritis (KOA) before and after electroacupuncture (EA) treatment.

Methods: An 8-week intervention with EA was performed on 3 subjects with KOA. IR sequencing of complementarity determining region 3 (CDR3) was performed using RNA extracted from peripheral blood T cells of KOA subjects prior to and at the end of the intervention, as well as healthy volunteers (controls) who matched the subjects in sex and age. Neutrophils were extracted from the plasma of healthy individuals, pretreatment patients, and posttreatment patients for further transcriptome sequencing.

Results: The D50, diversity index (DI), and Shannon entropy values of circulatory T-cells were significantly lower in pretreatment KOA patients compared to healthy controls. Posttreatment KOA samples displayed significant decreases in serum proinflammatory factors, IL-8 and IL-18 (P < 0.01), as well as a substantial reduction in serum matrix MMP-3 and MMP-13 (P < 0.01, P < 0.05). Transcriptome analysis revealed that the expression of CXCL2, IRF8, and PEAR1 (P < 0.05) was significantly higher in patients before the treatment than in the healthy population and was significantly down-regulated after the treatment. In contrast, the expression of SMPD3 (P < 0.05) showed the opposite trend.

Conclusion: EA may alleviate KOA by rebalancing T-cell homeostasis and improving systemic inflammation. At the same time, EA treatment can significantly enhance TCR diversity, reduce levels of proinflammatory factors, and increase levels of anti-inflammatory factors, thereby achieving therapeutic effects.

研究背景在这项研究中,我们利用免疫复合物(IR)测序技术分析了外周血T细胞受体的多样性,并利用转录组学分析了轻中度膝骨关节炎(KOA)患者在电针(EA)治疗前后外周血中性粒细胞mRNA的基因表达:方法:对3名KOA患者进行为期8周的电针干预。方法:对 3 名 KOA 受试者进行了为期 8 周的 EA 干预,并使用干预前和干预结束时从 KOA 受试者以及在性别和年龄上与受试者相匹配的健康志愿者(对照组)的外周血 T 细胞中提取的 RNA 对互补决定区 3(CDR3)进行了 IR 测序。从健康人、治疗前患者和治疗后患者的血浆中提取中性粒细胞,进一步进行转录组测序:结果:与健康对照组相比,KOA治疗前患者循环T细胞的D50、多样性指数(DI)和香农熵值明显较低。治疗后的 KOA 样本显示血清促炎因子 IL-8 和 IL-18 明显降低(P < 0.01),血清基质 MMP-3 和 MMP-13 也大幅降低(P < 0.01,P < 0.05)。转录组分析显示,治疗前,患者体内的CXCL2、IRF8和PEAR1(P<0.05)的表达明显高于健康人群,治疗后则明显下调。相比之下,SMPD3(P < 0.05)的表达则呈相反趋势:结论:EA 可通过重新平衡 T 细胞平衡和改善全身炎症来缓解 KOA。结论:EA 可通过重新平衡 T 细胞稳态和改善全身炎症来缓解 KOA,同时,EA 治疗可显著提高 TCR 多样性,降低促炎因子水平,提高抗炎因子水平,从而达到治疗效果。
{"title":"Electroacupuncture Ameliorates Knee Osteoarthritis By Rebalancing T Cell Homeostasis as Revealed By Immune Repertoire (IR) Sequencing.","authors":"Wenrui Jia, Yunan Zhang, Tianqi Wang, Cunzhi Liu, Jianfeng Tu, Guangxia Shi, LingYi Cai, Jingwen Yang, Guangrui Huang","doi":"10.2174/0113862073303471240805061026","DOIUrl":"https://doi.org/10.2174/0113862073303471240805061026","url":null,"abstract":"<p><strong>Background: </strong>In this study, we used immune repertoire (IR) sequencing technology to profile the diversity of peripheral blood T cell receptors and used transcriptomics to profile the gene expression of peripheral blood neutrophil mRNA in patients with mild-moderate knee osteoarthritis (KOA) before and after electroacupuncture (EA) treatment.</p><p><strong>Methods: </strong>An 8-week intervention with EA was performed on 3 subjects with KOA. IR sequencing of complementarity determining region 3 (CDR3) was performed using RNA extracted from peripheral blood T cells of KOA subjects prior to and at the end of the intervention, as well as healthy volunteers (controls) who matched the subjects in sex and age. Neutrophils were extracted from the plasma of healthy individuals, pretreatment patients, and posttreatment patients for further transcriptome sequencing.</p><p><strong>Results: </strong>The D50, diversity index (DI), and Shannon entropy values of circulatory T-cells were significantly lower in pretreatment KOA patients compared to healthy controls. Posttreatment KOA samples displayed significant decreases in serum proinflammatory factors, IL-8 and IL-18 (P < 0.01), as well as a substantial reduction in serum matrix MMP-3 and MMP-13 (P < 0.01, P < 0.05). Transcriptome analysis revealed that the expression of CXCL2, IRF8, and PEAR1 (P < 0.05) was significantly higher in patients before the treatment than in the healthy population and was significantly down-regulated after the treatment. In contrast, the expression of SMPD3 (P < 0.05) showed the opposite trend.</p><p><strong>Conclusion: </strong>EA may alleviate KOA by rebalancing T-cell homeostasis and improving systemic inflammation. At the same time, EA treatment can significantly enhance TCR diversity, reduce levels of proinflammatory factors, and increase levels of anti-inflammatory factors, thereby achieving therapeutic effects.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970787","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
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Combinatorial chemistry & high throughput screening
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