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Paroxetine alleviates ulcerative colitis in mice via restoring intestinal microbiota homeostasis and metabolism 帕罗西汀通过恢复肠道微生物群稳态和代谢来减轻小鼠溃疡性结肠炎。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-18 DOI: 10.1111/bcpt.14114
Minquan Zhang, Yuxin Zhou, Lianghui Huang, Weiman Hong, Yangbiao Li, Zhenhua Chen, Liangliang Zhou

Ulcerative colitis (UC) is an inflammatory bowel disease and psychological factors may be one of its pathogeneses. Selective serotonin reuptake inhibitor drug such as paroxetine with an effective anti-depression ability may be a new option for UC treatment. To evaluate the therapeutic effect of paroxetine on the exacerbation of UC symptoms caused by depression, a dual model of C57BL/6 mice was established using dextran sulphate sodium and chronic unpredictable mild stress (CUMS). Behavioural experiments, H&E staining and the level of 5-hydroxytryptamine (5-HT) in the brain were used to demonstrate successful replication of the CUMS model. The levels of 5-HT, TNF-α and IL-1β in the colon and the activity of MPO in the serum were determined by ELISA kits. The levels of some gut microbiota in the faeces were measured by qPCR and faecal differential metabolites were analysed by 1H NMR. The results indicate that CUMS can exacerbate UC symptoms in mice by exacerbating inflammation, and UC+CUMS can disrupt gut microbiota and fatty acid metabolism. Paroxetine can improve the mental state of mice, reduce serum MPO activity, but increase TNF-α and IL-1β levels in the colon. In addition, paroxetine also can restore the intestinal flora of mice and improve intestinal absorption and metabolic function of amino acids and short-chain fatty acids.

溃疡性结肠炎是一种炎症性肠病,心理因素可能是其发病机制之一。选择性血清素再摄取抑制剂药物如帕罗西汀具有有效的抗抑郁能力,可能是UC治疗的新选择。为评价帕罗西汀对抑郁症引起的UC症状加重的治疗作用,采用葡聚糖硫酸钠和慢性不可预测轻度应激(CUMS)建立C57BL/6小鼠双模型。行为学实验、H&E染色和脑内5-羟色胺(5-HT)水平证实了CUMS模型的成功复制。ELISA法检测大鼠结肠5-HT、TNF-α、IL-1β水平及血清MPO活性。通过qPCR测量粪便中一些肠道微生物群的水平,并通过1H NMR分析粪便差异代谢物。结果表明,CUMS可通过加重炎症加重小鼠UC症状,UC+CUMS可破坏肠道菌群和脂肪酸代谢。帕罗西汀能改善小鼠精神状态,降低血清MPO活性,升高结肠中TNF-α和IL-1β水平。此外,帕罗西汀还能恢复小鼠肠道菌群,改善肠道对氨基酸和短链脂肪酸的吸收和代谢功能。
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引用次数: 0
Optimizing autophagy modulation for enhanced TRAIL-mediated therapy: Unveiling the superiority of late-stage inhibition over early-stage inhibition to overcome therapy resistance in cancer 优化自噬调节以增强trail介导的治疗:揭示晚期抑制比早期抑制在克服癌症治疗耐药方面的优势。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-12 DOI: 10.1111/bcpt.14110
Kazi Mohammad Ali Zinnah, Ali Newaz Munna, Sang-Youel Park

Autophagy is a vital mechanism that eliminates large cytoplasmic components via lysosomal degradation to maintain cellular homeostasis. The role of autophagy in cancer treatment has been studied extensively. Autophagy primarily prevents tumour initiation by maintaining genomic stability and preventing cellular inflammation. However, autophagy also supports cancer cell survival and growth by providing essential nutrients for therapeutic resistance. Thus, autophagy has emerged as a promising strategy for overcoming resistance and enhancing anti-cancer therapy. Inhibiting autophagy significantly improves the sensitivity of lung, colorectal, breast, liver and prostate cancer cells to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). This review investigates the intricate interplay between autophagy modulation and TRAIL-based therapy, specifically focussing on comparing the efficacy of late-stage autophagy inhibition versus early-stage inhibition in overcoming cancer resistance. We expose the distinctive advantages of late-stage autophagy inhibition by exploring the mechanisms underlying autophagy's impact on TRAIL sensitivity. Current preclinical and clinical investigations are inspected, showing the potential of targeting late-stage autophagy for sensitizing resistant cancer cells to TRAIL-induced apoptosis. This review emphasizes the significance of optimizing autophagy modulation to enhance TRAIL-mediated therapy and overcome the challenge of treatment resistance in cancer. We offer insights and recommendations for guiding the development of potential therapeutic strategies aimed at overcoming the challenges posed by treatment-resistant cancers.

自噬是一种重要的机制,通过溶酶体降解消除大的细胞质成分,以维持细胞的稳态。自噬在癌症治疗中的作用已被广泛研究。自噬主要通过维持基因组稳定性和防止细胞炎症来防止肿瘤的发生。然而,自噬也通过为治疗抵抗提供必需的营养物质来支持癌细胞的生存和生长。因此,自噬已成为克服耐药性和加强抗癌治疗的一种有前途的策略。抑制自噬可显著提高肺癌、结直肠癌、乳腺癌、肝癌和前列腺癌细胞对肿瘤坏死因子相关凋亡诱导配体(TRAIL)的敏感性。这篇综述研究了自噬调节和基于trail的治疗之间复杂的相互作用,特别关注于比较晚期自噬抑制和早期抑制在克服癌症耐药方面的效果。我们通过探索自噬对TRAIL敏感性影响的潜在机制,揭示了晚期自噬抑制的独特优势。目前的临床前和临床研究都显示了靶向晚期自噬使耐药癌细胞对trail诱导的细胞凋亡敏感的潜力。这篇综述强调了优化自噬调节对增强trail介导的治疗和克服癌症治疗耐药挑战的意义。我们为指导潜在治疗策略的发展提供见解和建议,旨在克服治疗抵抗性癌症带来的挑战。
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引用次数: 0
CaMKIIα hub ligands are unable to reverse known phenotypes in Angelman syndrome mice CaMKIIα中枢配体不能逆转Angelman综合征小鼠的已知表型。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-12 DOI: 10.1111/bcpt.14112
Stine J. Gauger, Maria E. K. Lie, Ilse Wallaard, Yongsong Tian, Aleš Marek, Bente Frølund, Geeske M. van Woerden, Ype Elgersma, Birgitte R. Kornum, Petrine Wellendorph

Angelman Syndrome (AS) is a neurodevelopmental disorder caused by the loss of function of ubiquitin-protein ligase E3A (UBE3A), resulting in marked changes in synaptic plasticity. In AS mice, a dysregulation of Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIα) was previously described. This has been convincingly validated through genetic rescue of prominent phenotypes in mouse cross-breeding experiments. Selective ligands that specifically stabilize the CaMKIIα central association (hub) domain and affect different conformational states in vitro are now available. Two of these ligands, 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) and (E)-2-(5-hydroxy-2-phenyl-5,7,8,9-tetrahydro-6H-benzo[7]annulen-6-ylidene)acetic acid (Ph-HTBA), confer neuroprotection after ischemic stroke in mice where CaMKIIα is known to be dysregulated. Here, we sought to investigate whether pharmacological modulation with these prototypical CaMKIIα hub ligands presents a viable approach to alleviate AS symptoms. We performed an in vivo functional evaluation of AS mice treated for a total of 14 days with either HOCPCA or Ph-HTBA (7 days pre-treatment and 7 days of behavioural assessment). Both compounds were well-tolerated but unable to revert robust phenotypes of motor performance, anxiety, repetitive behaviour or seizures in AS mice. Biochemical experiments subsequently assessed CaMKIIα autophosphorylation in AS mouse brain tissue. Taken together our results indicate that pharmacological modulation of CaMKIIα via the selective hub ligands used here is not a viable treatment strategy in AS.

Angelman综合征(AS)是一种泛素蛋白连接酶E3A (UBE3A)功能丧失导致突触可塑性明显改变的神经发育障碍。在AS小鼠中,先前描述了Ca2+/钙调素依赖性蛋白激酶IIα (CaMKIIα)的失调。这已经通过小鼠杂交实验中突出表型的遗传拯救得到了令人信服的验证。选择性配体特异性稳定CaMKIIα中心结合(hub)结构域,并在体外影响不同的构象状态。其中两种配体,3-羟基环戊-1-烯羧酸(HOCPCA)和(E)-2-(5-羟基-2-苯基-5,7,8,9-四氢- 6h -苯并bb0环烯-6-酰基)乙酸(Ph-HTBA),在已知CaMKIIα失调的小鼠缺血性中风后具有神经保护作用。在这里,我们试图研究这些原型CaMKIIα中枢配体的药理学调节是否提供了一种缓解AS症状的可行方法。我们对接受HOCPCA或Ph-HTBA共14天治疗的AS小鼠进行了体内功能评估(预处理7天,行为评估7天)。这两种化合物都具有良好的耐受性,但不能恢复AS小鼠的运动表现、焦虑、重复行为或癫痫发作的强劲表型。生化实验随后评估了CaMKIIα在AS小鼠脑组织中的自磷酸化。综上所述,我们的研究结果表明,通过选择性中心配体对CaMKIIα进行药理学调节并不是一种可行的治疗AS的策略。
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引用次数: 0
Investigating the P53-dependent anti-cancer effect of ibutamoren in human cancer cell lines 研究依p53依赖性的伊布他莫伦在人癌细胞系中的抗癌作用。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-12 DOI: 10.1111/bcpt.14111
Naeem Abdul Ghafoor, Sabina Rasuli, Özgür Tanriverdi, Ayşegül Yildiz

The MDM2-p53 pathway plays a pivotal role in regulating cell cycle and apoptosis, with its dysfunction contributing to approximately 50% of human malignancies. MDM2, an E3 ubiquitin ligase, targets the tumour suppressor p53 for degradation, thereby promoting uncontrolled cell growth in cancers. Inhibiting the MDM2-p53 interaction represents a promising therapeutic strategy for reactivating p53’s tumour-suppressive functions. This study explored the potential of ibutamoren (IBU) as a novel inhibitor of MDM2. In silico analyses utilizing molecular modelling revealed that IBU has a low IC50 for MDM2 inhibition and favourably binds to the p53-binding pocket of MDM2. In vitro experiments demonstrated that IBU treatment reduced the viability of immortalized cancer cell lines with a functional MDM2-p53 pathway but not in cell lines where this pathway harboured damaging mutations. This trend was further supported by RT-qPCR analysis, which showed differential expression of two p53 target genes upon IBU treatment in cell lines with wild MDM2-p53 pathways but not in those harbouring damaging mutations. These findings provide preliminary evidence supporting IBU's anticancer activity, plausibly through the MDM2-p53 pathway, and suggest that further studies are warranted to explore its mechanism of action and potential development as a lead compound in oncology research.

MDM2-p53通路在调节细胞周期和细胞凋亡中起着关键作用,其功能障碍导致了大约50%的人类恶性肿瘤。MDM2是一种E3泛素连接酶,靶向肿瘤抑制因子p53降解,从而促进癌症中不受控制的细胞生长。抑制MDM2-p53相互作用是一种很有前途的治疗策略,可以重新激活p53的肿瘤抑制功能。本研究探讨了ibutamoren (IBU)作为一种新型MDM2抑制剂的潜力。利用分子模型的硅分析显示,IBU对MDM2的抑制作用具有较低的IC50,并且有利于与MDM2的p53结合口袋结合。体外实验表明,IBU治疗降低了具有功能MDM2-p53通路的永生化癌细胞系的生存能力,但在该通路含有破坏性突变的细胞系中则没有。RT-qPCR分析进一步支持了这一趋势,该分析显示,在具有野生MDM2-p53通路的细胞系中,IBU处理后两个p53靶基因的表达存在差异,而在具有破坏性突变的细胞系中则没有差异。这些发现为IBU的抗癌活性提供了初步证据,可能是通过MDM2-p53途径,并表明有必要进一步研究其作用机制和作为肿瘤研究先导化合物的潜力。
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引用次数: 0
BCPT perspectives on studies involving natural products, traditional Chinese medicine and systems pharmacology 从天然产物、中药和系统药理学的角度看BCPT的研究。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 DOI: 10.1111/bcpt.14109
Pernille Tveden-Nyborg, Baoxue Yang, Ulf Simonsen, Jens Lykkesfeldt

Natural products constitute a vast source of bioactive compounds with the potential of providing valuable insight for future medicines. However, from a pharmacological perspective, natural product studies are also often accompanied by serious limitations due to, for example, the complex nature of biological extracts, the challenge of reproducibly characterizing the extract and providing an exhaustive list of constituents and, consequently, the difficulties in linking the observed pharmacological effects to specific chemical entities. The present paper discusses the major challenges of studies with natural products and provides a guideline to be followed by authors submitting research findings involving data from natural products, and their derivatives, to Basic & Clinical Pharmacology & Toxicology.

天然产物构成了生物活性化合物的巨大来源,具有为未来药物提供有价值见解的潜力。然而,从药理学的角度来看,天然产物研究也常常伴随着严重的局限性,例如,由于生物提取物的复杂性,对提取物进行可重复性表征和提供详尽的成分列表的挑战,以及将观察到的药理作用与特定化学实体联系起来的困难。本文讨论了天然产物研究的主要挑战,并提供了一个指南,供作者在基础与临床药理学与毒理学上提交涉及天然产物及其衍生物数据的研究结果时遵循。
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引用次数: 0
Limited sampling approach for model-informed precision dosing of daptomycin to rapidly achieving the target area under the concentration-time curve: A simulation study 以模型为依据的达托霉素精确给药的有限采样方法可快速达到目标浓度-时间曲线下面积:模拟研究。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-26 DOI: 10.1111/bcpt.14108
Tomoyuki Yamada, Kazutaka Oda, Masami Nishihara, Akira Ashida

Daptomycin, an anti-methicillin-resistant Staphylococcus aureus drug, causes exposure-dependent muscle toxicity and eosinophilic pneumonia. Although the area under the concentration-time curve (AUC)-guided dosing is crucial, an optimal blood sampling strategy is lacking. This study aimed to identify an optimal limited sampling strategy using Bayesian forecasting to rapidly achieve the target AUC. Two validated population pharmacokinetic models generated a virtual population of 1000 individuals (models 1 and 2 represent diverse patients and kidney transplant recipients, respectively). The AUC for each blood sample was assessed using the probability of achieving the estimated/reference AUC ratio on the second day (AUC24–48) and at the steady state (AUCss). In Model 1, Bayesian posterior probabilities for AUC24–48 increased from 50.7% (a priori) to 59.4% and for AUCss from 48.9% (a priori) to 61.9%, with one-point Ctrough sampling at 24 h. With two-point sampling at 7 and 24 h, the probabilities increased to 73.8% for AUC24–48 and 69.7% for AUCss. In Model 2, the probabilities for both AUC24–48 and AUCss with one-point Ctrough or two-point sampling incorporating Ctrough sampling increased compared to a priori probabilities. These results suggest that two-point sampling incorporating Ctrough during initial dosing enhanced achieving the target AUC24–48 and AUCss rapidly.

达托霉素是一种抗耐甲氧西林金黄色葡萄球菌药物,会导致暴露依赖性肌肉毒性和嗜酸性粒细胞肺炎。虽然浓度-时间曲线下面积(AUC)指导用药至关重要,但目前还缺乏最佳的血液采样策略。本研究旨在利用贝叶斯预测法确定最佳有限采样策略,以快速达到目标 AUC。两个经过验证的群体药代动力学模型生成了一个由 1000 人组成的虚拟群体(模型 1 和 2 分别代表不同的患者和肾移植受者)。使用第二天(AUC24-48)和稳态(AUCss)达到估计/参考 AUC 比率的概率来评估每个血样的 AUC。在模型 1 中,24 小时单点 Ctrough 采样,AUC24-48 的贝叶斯后验概率从 50.7%(先验)增加到 59.4%,AUCss 从 48.9%(先验)增加到 61.9%。在模型 2 中,与先验概率相比,单点 Ctrough 或包含 Ctrough 采样的两点采样的 AUC24-48 和 AUCss 的概率都有所提高。这些结果表明,在初始给药过程中进行包含 Ctrough 的两点取样可快速达到目标 AUC24-48 和 AUCss。
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引用次数: 0
Diloxanide in amoebiasis management: Unravelling the mechanism of action and effectiveness 地洛沙尼在阿米巴病治疗中的应用:揭示作用机制和有效性。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-20 DOI: 10.1111/bcpt.14106
Samuel Inshutiyimana, Michael Matiop Aleu, Mustaf Aden Abdinoor, Mariyah Murtaza Janoowalla, Norhayati Norhayati

Although diloxanide is a drug of choice for treating asymptomatic amoebiasis, its mechanism of action (MOA) remains unclear. This review aims to shed light on the current understanding of the effectiveness and MOA of diloxanide in treating amoebiasis . It involves analysis of articles, retrieved from PubMed, Google Scholar and EBSCOhost, on diloxanide and the treatment of Entamoeba histolytica infection. Diloxanide is used in an ester form, which allows its high luminal concentration and greater efficacy than metronidazole in the management of asymptomatic amoebiasis. The current understanding of the action of diloxanide is based on its structural similarity to chloramphenicol at dichloroacetamide group. It acts against protein synthesis in E. histolytica trophozoites, blocking their conversion to more virulent and invasive cyst forms. Furthermore, it has a parasite clearance rate of 81–96% and treats amoebic abscesses when combined with metronidazole and chloroquine. Nevertheless, it is associated with adverse events such as flatulence, anorexia, headache and urticaria. Diloxanide is efficacious against amoebiasis but there is a need to explore its structure–activity relationship.The study suggests future directions, including novel drug formulations, diagnostic improvements, and combination regimens to enhance treatment outcomes and mitigate relapse associated with the use of diloxanide.

尽管地洛沙尼是治疗无症状阿米巴病的首选药物,但其作用机制(MOA)仍不明确。本综述旨在阐明目前对地洛沙尼治疗阿米巴病的有效性和作用机制的认识。文章分析了从 PubMed、Google Scholar 和 EBSCOhost 上检索到的有关地洛沙尼和治疗组织溶解恩塔米巴虫感染的文章。地洛沙内酯以酯类形式使用,在治疗无症状阿米巴病时,其腔内浓度高,疗效优于甲硝唑。目前对地洛沙内酯作用的了解是基于它与氯霉素在二氯乙酰胺基团上的结构相似性。它能抑制组织溶解埃希氏菌滋养体的蛋白质合成,阻止其转化为毒性更强的侵袭性包囊形式。此外,它的寄生虫清除率高达 81-96%,与甲硝唑和氯喹合用可治疗阿米巴脓肿。不过,该药也有不良反应,如胀气、厌食、头痛和荨麻疹。该研究提出了未来的发展方向,包括新型药物制剂、诊断改进和联合疗法,以提高治疗效果并减少与使用地洛沙尼相关的复发。
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引用次数: 0
Long-term taurine supplementation regulates brain mitochondrial dynamics in mice 长期补充牛磺酸可调节小鼠大脑线粒体的动态变化。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-18 DOI: 10.1111/bcpt.14101
Heresh Rezaei, Hong-Wei Wang, Weishun Tian, Jing Zhao, Asma Najibi, Socorro Retana-Márquez, Elahe Rafiei, Ayeh Rowhanirad, Samira Sabouri, Mohammadreza Kiafar, Rahil Fazlinezhad, Amir Mohammad Niknahad, Fatemeh Evazzadeh, Seyedeh Tayebeh Anousheh, Mohammad Mehdi Ommati, Hossein Niknahad, Reza Heidari

Background

Taurine (TAU) is the most abundant non-protein amino acid in the central nervous system (CNS). However, the molecular mechanism of TAU in the CNS is still poorly understood. Meanwhile, disruption in mitochondrial dynamics is evident in CNS disorders. This study aimed to investigate the effect of TAU on mitochondrial dynamics.

Methods

TAU (0.25, 0.5 and 1% in drinking water) was administered to young mice for six months. Several memory/cognition parameters and indices of anxiety/depression were assessed. Meanwhile, various mitochondrial indices and the expression/activity of genes involved in mitochondrial biogenesis and dynamics (Akt, CREB, NRF1, TFAM, PGC-1α, Mfn1, Mfn2, UCP2, PINK1, OPA1, Drp1 and Fis1) were examined.

Results

TAU significantly enhanced memory performance, suppressed anxiety and depression-like behaviour, increased mitochondrial biogenesis/dynamics and improved mitochondrial indices. It should be mentioned that there was no significant difference between different concentrations of TAU in changing most brain mitochondrial dynamic biomarkers in the current study.

Conclusions

These findings offer more insights into the molecular mechanism for TAU's action in the CNS. However, there is a need for further research to confirm these effects in humans. Overall, this study suggests the potential application of TAU in various neurological disorders and the need for clinical studies on the effects of this amino acid in the brain.

背景:牛磺酸(TAU)是中枢神经系统(CNS)中含量最高的非蛋白氨基酸。然而,人们对牛磺酸在中枢神经系统中的分子机制仍知之甚少。同时,线粒体动力学的破坏在中枢神经系统疾病中十分明显。本研究旨在探讨TAU对线粒体动力学的影响:方法:给幼年小鼠注射 TAU(0.25%、0.5% 和 1% 的饮用水),为期 6 个月。方法:给幼鼠注射 TAU(在饮用水中分别添加 0.25、0.5 和 1%)6 个月,评估其记忆/认知参数以及焦虑/抑郁指数。同时,还检测了各种线粒体指数以及参与线粒体生物生成和动力学的基因(Akt、CREB、NRF1、TFAM、PGC-1α、Mfn1、Mfn2、UCP2、PINK1、OPA1、Drp1和Fis1)的表达/活性:结果:TAU能明显提高记忆力,抑制焦虑和抑郁行为,增加线粒体生物生成/动力学,改善线粒体指数。值得一提的是,在本研究中,不同浓度的TAU在改变大多数脑线粒体动态生物标志物方面没有明显差异:这些研究结果为TAU在中枢神经系统中发挥作用的分子机制提供了更多见解。然而,还需要进一步的研究来证实这些作用对人体的影响。总之,这项研究表明 TAU 有可能应用于各种神经系统疾病,而且有必要对这种氨基酸在大脑中的作用进行临床研究。
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引用次数: 0
Syringin ameliorates dextran sulphate colitis via alteration oxidative stress, inflammation NF-κB signalling pathway and gut microbiota 丁香素通过改变氧化应激、炎症NF-κB信号通路和肠道微生物群来改善硫酸葡聚糖结肠炎
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-16 DOI: 10.1111/bcpt.14105
Juhui Zhao, Qingqing Zhang, Xudong Hao

Background

The objective of the current study was to investigate the potential effects of syringin against dextran sulphate colitis (DSS)-induced ulcerative colitis (UC) in mice.

Material and methods

In vitro study was performed on the RAW 264.7 cells and cytokines and inflammatory level were estimated. The oxidative stress, inflammatory cytokines, apoptosis and inflammatory parameters were estimated. The mRNA expression and faecal samples were estimated in the colon tissue.

Results

Syringin treatment enhanced the body weight, colon length and reduced the disease activity index (DAI), spleen index. Syringin treatment remarkably suppressed the level of nitric oxide (NO), myeloperoxidase (MPO), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) along with alteration of antioxidant parameters. Syringin treatment also altered level of cytokines in the serum and colon tissue; inflammatory parameters viz., platelet-activating factor (PAF), cyclooxygenase-2 (COX-2), prostaglandin (PGE2), inducible nitric oxide synthetase (iNOS), nuclear factor κ-B (NF-κB); matrix metalloproteinases (MMP) level. Syringin significantly (p < 0.001) enhanced the level of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1). Syringin remarkably altered the relative abundance of gut microbiota like Firmicutes, Bacteroidetes, F/B ratio, Verrucomicrobia and Actinobacteria.

Conclusion

Syringin exhibited the protective effect against DSS-induced UC in mice via alteration of NF-κB signalling pathway.

背景:本研究旨在探讨丁香素对硫酸右旋糖酐结肠炎(DSS)诱导的小鼠溃疡性结肠炎(UC)的潜在作用:对 RAW 264.7 细胞进行体外研究,评估细胞因子和炎症水平。对氧化应激、炎症细胞因子、细胞凋亡和炎症参数进行了估计。对结肠组织中的 mRNA 表达和粪便样本进行了估计:结果:鞘氨醇治疗提高了患者的体重和结肠长度,降低了疾病活动指数(DAI)和脾脏指数。鞘氨醇治疗显著抑制了一氧化氮(NO)、髓过氧化物酶(MPO)、细胞间粘附分子-1(ICAM-1)和血管细胞粘附分子-1(VCAM-1)的水平,并改变了抗氧化参数。丁香素还改变了血清和结肠组织中的细胞因子水平;炎症参数,即血小板活化因子(PAF)、环氧化酶-2(COX-2)、前列腺素(PGE2)、诱导型一氧化氮合成酶(iNOS)、核因子κ-B(NF-κB);基质金属蛋白酶(MMP)水平。紫丁香苷明显(p 2)影响血红素加氧酶-1(HO-1)。人参皂苷明显改变了肠道微生物群的相对丰度,如固着菌、类杆菌、F/B 比率、Verrucomicrobia 和放线菌:结论:Syringin通过改变NF-κB信号通路对DSS诱导的小鼠UC具有保护作用。
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引用次数: 0
Amount, type and storage of medicines in households – A survey for medicine users 家庭药品的数量、种类和储存--针对药品使用者的调查。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-14 DOI: 10.1111/bcpt.14104
Mella Louhisalmi, Piia Lavikainen, Kari Linden, Janne Martikainen, Johanna Timonen

With increasing medicine use, more medicines are being stored at home, yet the understanding of household medicines remains limited. This study aimed to assess the amount, type and storage practices of medicines in households. It also explored the reasons for unnecessary or expired medicines, as well as the factors associated with the presence of expired medicines in a household. The online survey was conducted among loyal customers of University Pharmacy in June 2023 (n = 5004). The data were analysed for frequencies and percentages, and binary logistic regression was used to examine the association between background factors and expired medicines in households. On average, one household had 13.9 active, 2.8 unnecessary and 2.2 expired medicine packs. Medicines were typically stored in the kitchen (67.0%) and in cabinets (58.7%), and 40% were to be stored safely. The main reasons for unnecessary or expired medicines were improved health (39.2%), medication changes (31.9%) and oversized packs (28.0%). Households returning medicines biennially (odds ratio (OR): 2.85; 95% confidence interval (CI): 2.13–3.82) and those with many active medicines (OR: 2.14; 95% CI: 1.79–2.54) had expired medicines more often. The study showed that households had many medicines, highlighting the need for better storage and optimized packaging to improve safety, reduce waste and enhance rational pharmacotherapy.

随着药品使用量的增加,越来越多的药品被储存在家中,但人们对家庭药品的了解仍然有限。本研究旨在评估家庭中药品的数量、类型和储存方式。它还探讨了不必要的药品或过期药品的原因,以及家庭中存在过期药品的相关因素。在线调查于 2023 年 6 月在大学药房的忠实顾客中进行(n = 5004)。对数据进行了频率和百分比分析,并采用二元逻辑回归法研究了背景因素与家庭中过期药品之间的关联。一个家庭平均有 13.9 个有效药包、2.8 个不必要药包和 2.2 个过期药包。药品通常存放在厨房(67.0%)和橱柜(58.7%)中,40%的药品应安全存放。不必要或过期药品的主要原因是健康状况改善(39.2%)、换药(31.9%)和药包过大(28.0%)。每两年归还一次药品的家庭(几率比(OR):2.85;95% 置信区间(CI):2.13-3.82)和拥有许多有效药品的家庭(OR:2.14;95% 置信区间(CI):1.79-2.54)更经常出现药品过期的情况。研究结果表明,家庭中的药品数量较多,因此需要更好地储存和优化包装,以提高安全性、减少浪费并加强合理的药物治疗。
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Basic & Clinical Pharmacology & Toxicology
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