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Exploring the role of sex in asthma and COPD pharmacological treatment 探讨性别在哮喘和慢性阻塞性肺病药物治疗中的作用
Q2 Agricultural and Biological Sciences Pub Date : 2025-01-01 DOI: 10.1016/j.crphar.2025.100234
Luigino Calzetta , Shima Gholamalishahi , Elena Pistocchini , Bartolomeo Zerillo , Maria Gabriella Matera , Paola Rogliani
Sex is a fundamental determinant in pharmacology, influencing disease prevalence, severity, and therapeutic responses. Differences in pharmacokinetics and pharmacodynamics between men and women contribute to variations in drug efficacy and safety profiles. While sex refers to biological and physiological characteristics, gender encompasses social and behavioral factors. Despite their distinct meanings, these terms are often used interchangeably in medical research, potentially leading to misinterpretations. Historically, female and intersex individuals have been underrepresented in clinical studies, resulting in biased treatment approaches. Acknowledging these disparities, researchers now emphasize the importance of sex-specific differences to enhance therapeutic outcomes.
This review explores the impact of sex on the pharmacological treatment of chronic obstructive respiratory diseases, particularly asthma and chronic obstructive pulmonary disease (COPD).
Asthma is more prevalent in women, whereas COPD severity is rising among female patients. Sex influences the response to bronchodilators, inhaled corticosteroids (ICS), and combination therapies. Studies suggest that men exhibit a greater response to β2-adrenoceptor agonists and sex differences in muscarinic acetylcholine receptor (mAChR) expression may influence bronchodilator response to muscarinic antagonists. Moreover, women display stronger immune responses and higher corticosteroid receptor expression, potentially modulating the efficacy of ICS. Women are also more likely to experience adverse drug reactions and face challenges in correct inhaler device use, impacting treatment adherence and clinical outcomes. Despite these differences between men and women, sex-specific approaches remain insufficiently integrated into clinical practice. Addressing sex disparities in pharmacotherapy is crucial to optimize treatment strategies. Further research is needed to elucidate sex-related differences and incorporate them into evidence-based guidelines for asthma and COPD management.
在药理学中,性别是一个基本的决定因素,影响疾病的流行、严重程度和治疗反应。男性和女性在药代动力学和药效学上的差异导致了药物疗效和安全性的差异。性指的是生物和生理特征,而性别则包括社会和行为因素。尽管这些术语的含义不同,但在医学研究中经常互换使用,这可能会导致误解。从历史上看,女性和双性人在临床研究中的代表性不足,导致治疗方法存在偏见。认识到这些差异,研究人员现在强调了性别特异性差异对提高治疗效果的重要性。这篇综述探讨了性别对慢性阻塞性呼吸系统疾病,特别是哮喘和慢性阻塞性肺疾病(COPD)药物治疗的影响。哮喘在女性中更为普遍,而COPD在女性患者中的严重程度正在上升。性别影响对支气管扩张剂、吸入皮质类固醇(ICS)和联合治疗的反应。研究表明,男性对β2-肾上腺素受体激动剂表现出更大的反应,毒蕈碱乙酰胆碱受体(mAChR)表达的性别差异可能影响支气管扩张剂对毒蕈碱拮抗剂的反应。此外,女性表现出更强的免疫反应和更高的皮质类固醇受体表达,可能调节ICS的疗效。女性也更有可能出现药物不良反应,并在正确使用吸入器装置方面面临挑战,从而影响治疗依从性和临床结果。尽管男性和女性之间存在这些差异,但针对性别的方法仍未充分纳入临床实践。解决药物治疗中的性别差异对于优化治疗策略至关重要。需要进一步的研究来阐明与性别相关的差异,并将其纳入哮喘和COPD管理的循证指南。
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引用次数: 0
Probing into the chemopreventive properties of synthetic 1,3,6-tri-O-galloyl-α-D-glucose (α-TGG) against glioblastoma and triple-negative breast cancer-derived cell models 探讨合成1,3,6-三- o -没食子酰-α- d -葡萄糖(α-TGG)对胶质母细胞瘤和三阴性乳腺癌源性细胞模型的化学预防作用
Q2 Agricultural and Biological Sciences Pub Date : 2025-01-01 DOI: 10.1016/j.crphar.2025.100219
Carolane Veilleux , Jihane Khalifa , Alain Zgheib , Angélique Sabaoth Konan , Roger Gaudreault , Borhane Annabi
Inflammation plays a significant role in cancer progression. Chemopreventive strategies against cellular response to pro-inflammatory cues may therefore contribute to inhibit the acquisition of an invasive phenotype. 1,3,6-Tri-O-Galloyl-β-D-Glucose (β-TGG) is a type of gallotannin naturally found in plants like Paeonia lactiflora and Terminalia chebula. Unfortunately, the overall yields of β-TGG extraction require complex purification protocols from plant sources and are relatively low. Here, a new synthetic α-anomer of TGG (α-TGG) was characterized for anti-inflammatory and anticancer biological properties. In vitro pro-inflammatory and epithelial-to-mesenchymal transition (EMT) cues, triggered by phorbol 12-myristate 13-acetate (PMA), concanavalin A (ConA), tumor necrosis factor (TNF) α, and transforming growth factor (TGF) β, were used to screen α-TGG in two highly aggressive human cancer cell models, namely the U87 glioblastoma and the MDA-MB-231 triple-negative breast cancer (TNBC)-derived cells. α-TGG dose-dependently inhibited ConA-mediated activation of the latent matrix metalloproteinase pro-MMP-2 into its active MMP-2 form as well as the ConA- and PMA-mediated cyclooxygenase (COX)-2 expression, two biomarkers of inflammation, in U87 cells. In MDA-MB-231, α-TGG inhibited PMA- and TNFα-mediated induction of pro-MMP-9, a marker of inflammation and invasive phenotype. Finally, in both cell lines, α-TGG further inhibited TGFβ-induced chemotaxis, as well as TGFβ-induced Smad2 phosphorylation and Snail expression, crucial upstream signaling pathway and downstream biomarkers associated with EMT. Collectively, we confirm that α-TGG retained potent anti-inflammatory and anti-invasive pharmacological properties which support its chemopreventive potential.
炎症在癌症进展中起着重要作用。因此,针对细胞对促炎线索的反应的化学预防策略可能有助于抑制侵入性表型的获得。1,3,6-三- o -没食子酰-β- d -葡萄糖(β-TGG)是一种天然存在于芍药和chebula等植物中的没食子酰素。不幸的是,β-TGG提取的总体产量需要复杂的植物源纯化方案,并且相对较低。本文合成了一种新的TGG α-异头物(α-TGG),具有抗炎和抗癌的生物学特性。采用体外促炎和上皮-间质转化(EMT)信号,分别由phorbol 12-肉豆肉酸13-乙酸酯(PMA)、魔豆蛋白A (ConA)、肿瘤坏死因子(TNF) α和转化生长因子(TGF) β触发,在两种高侵袭性人肿瘤细胞模型(U87胶质母细胞瘤和MDA-MB-231三阴性乳腺癌(TNBC)来源细胞中筛选α- tgg。α-TGG剂量依赖性地抑制了ConA介导的潜在基质金属蛋白酶pro-MMP-2向活性MMP-2形式的激活,以及ConA-和pma介导的两种炎症生物标志物环氧化酶(COX)-2的表达。在MDA-MB-231中,α-TGG抑制PMA-和tnf - α介导的促mmp -9的诱导,促mmp -9是炎症和侵袭表型的标志。最后,在这两种细胞系中,α-TGG进一步抑制tgf β诱导的趋化性,以及tgf β诱导的Smad2磷酸化和Snail表达,这是与EMT相关的重要上游信号通路和下游生物标志物。总的来说,我们证实α-TGG保留了有效的抗炎和抗侵袭药理特性,这支持了其化学预防潜力。
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引用次数: 0
Real-world clinical utility (effectiveness) of omalizumab as add-on therapy in patient with difficult-to-treat severe allergic asthma 奥马珠单抗作为难以治疗的严重过敏性哮喘患者的附加疗法的实际临床效用(有效性
Q2 Agricultural and Biological Sciences Pub Date : 2025-01-01 DOI: 10.1016/j.crphar.2025.100218
Rowshne Jahan, Ziaul Huq

Background

Severe allergic asthma (SAA) requires high-dose inhaled corticosteroids and additional medications. It poses a substantial health and financial burden. Omalizumab, an antibody that targets IgE, has improved symptoms and quality of life in severe allergic asthma (SAA) patients. Its impact in Bangladeshi patients is unknown, and this study aimed to evaluate its effectiveness in improving lung function in severe allergic asthma (SAA) patients.

Methods

This single-centre, real-world study aimed to assess omalizumab's effectiveness in 131 Bangladeshi patients with SAA. Information regarding demographics, BMI, and IgE levels, were collected from patients >12 years with poorly controlled SAA before and 3 months after omalizumab treatment. Pulmonary function tests (PFTs), including Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 s (FEV1 %), FEV1/FVC (%), and Fractional Exhaled Nitric Oxide (FeNO), were performed according to established guidelines. A structured questionnaire was used for data collection. Ethical measures were taken in accordance with the current Declaration of Helsinki.

Results

The mean age of study population was 42.7 ± 16.15 (SD) years with majority being female (67.9 %). The mean BMI and IgE level was 28 ± 5.37 kg/m2 and 594.3 ± 679.9 IU/mL respectively. The mean baseline FVC, FEV1 and FEV1/FVC ratio was 63.5 % ± 19.2, 61.3 % ± 21.8 and 80.4 % ± 12.6 respectively. The mean post-omalizumab FVC, FEV1 and FEV1/FVC ratio was 72.5 % ± 25.6, 68.3 % ± 28.2 and 79.1 % ± 13.8 respectively. The FeNO reading revealed that number of patients with <25 ppb reading increased post omalizumab treatment (70.2 % vs 84 %).FEV1 expressed was significantly higher in patients post-omalizumab treatment than at the baseline (p = 0.019) and percentage of patients with FEV1 below the predicted 50 % was higher at baseline compared to after omalizumab treatment (31.3 % vs 23.7 %). Similarly, the FVC was significantly higher post-omalizumab treatment compared to baseline (p = 0.001). The FEV1/FVC ratio was not significantly different post omalizumab treatment (p = 0.758).

Conclusion

Our study finding have suggested that omalizumab as add on therapy achieved an adequate asthma control in patients with severe allergic asthma.
背景:严重过敏性哮喘(SAA)需要大剂量吸入皮质类固醇和其他药物治疗。它造成了巨大的健康和财政负担。Omalizumab是一种靶向IgE的抗体,可改善严重过敏性哮喘(SAA)患者的症状和生活质量。其对孟加拉国患者的影响尚不清楚,本研究旨在评估其改善严重过敏性哮喘(SAA)患者肺功能的有效性。本研究旨在评估omalizumab在131例孟加拉国SAA患者中的有效性。在奥玛单抗治疗前和治疗后3个月,收集了12年SAA控制不佳的患者的人口统计学、BMI和IgE水平信息。肺功能测试(PFTs),包括用力肺活量(FVC)、1s用力呼气量(FEV1 %)、FEV1/FVC(%)和呼气一氧化氮分数(FeNO),均按照既定指南进行。数据收集采用结构化问卷。按照目前的《赫尔辛基宣言》采取了道德措施。结果研究人群平均年龄为42.7±16.15 (SD)岁,女性居多(67.9%)。BMI平均值为28±5.37 kg/m2, IgE平均值为594.3±679.9 IU/mL。平均基线FVC、FEV1和FEV1/FVC比值分别为63.5%±19.2、61.3%±21.8和80.4%±12.6。平均FVC、FEV1和FEV1/FVC比值分别为72.5%±25.6、68.3%±28.2和79.1%±13.8。FeNO读数显示,奥玛珠单抗治疗后,读数为<; 25ppb的患者数量增加(70.2%对84%)。omalizumab治疗后患者FEV1的表达明显高于基线(p = 0.019), FEV1低于预测的50%的患者百分比在基线时高于omalizumab治疗后(31.3%对23.7%)。同样,与基线相比,奥玛珠单抗治疗后FVC显著升高(p = 0.001)。奥玛珠单抗治疗后FEV1/FVC比值无显著差异(p = 0.758)。结论我们的研究结果表明,奥玛珠单抗加药治疗对严重过敏性哮喘患者达到了充分的哮喘控制。
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引用次数: 0
Unveiling the mechanisms of synthetic compounds against Candida auris: An integrative review 揭示合成化合物抗耳念珠菌的机制:综合综述
Q2 Agricultural and Biological Sciences Pub Date : 2025-01-01 DOI: 10.1016/j.crphar.2025.100231
Yamini Saini , Zeeshan Fatima , Muriel Billamboz , Saif Hameed
The multidrug-resistant fungal species Candida auris has drawn attention from across the world due to its capacity to elude traditional therapies and flourish in medical environments. Its resilience, which includes biofilm development and efflux-mediated drug resistance, highlighted the need for novel antifungal approaches. Despite advancements in antifungal therapeutics, the rising prevalence of resistance and limited antifungal arsenal demand ongoing research into novel and more effective treatments. To tackle this rising issue, the available literature suggests several approaches. Among those, the use of synthetic compounds (SCs) appears as first-line option. However, to prove the efficacy of these SCs against C. auris a complete coverage is still elusive in a single study. Thus, in this integrative review, we aimed to summarize the anti-C. auris SCs that are reported in literature. About 47 articles were included in this review using predefined selection criteria. Data were extracted for detailed reviews from PubMed, Google scholar and Science direct. All the included studies tested antifungal activities of the SCs and evaluated their mode of actions. These data highlighted diverse modes of action such as perturbation of biofilm formation, disruption of cell wall and organelles, inhibition of efflux and generation of reactive oxygen species to name few. Taken together, SCs represent viable candidates for effective antifungal treatment. The information gathered in the present study emphasizes the need for further investigations, including preclinical studies and clinical trials, to evaluate the therapeutic potential of these agents against C. auris.
耐多药真菌品种耳念珠菌因其能够避开传统疗法并在医疗环境中蓬勃发展而引起了全世界的关注。它的弹性,包括生物膜的发育和外排介导的耐药性,强调了新的抗真菌方法的需要。尽管在抗真菌治疗方面取得了进展,但不断上升的耐药性和有限的抗真菌武器库需要持续研究新的和更有效的治疗方法。为了解决这个日益严重的问题,现有文献提出了几种方法。其中,使用合成化合物(SCs)似乎是一线选择。然而,为了证明这些SCs对金黄色葡萄球菌的疗效,在单一的研究中仍然难以完全覆盖。因此,在这篇综合综述中,我们旨在总结抗c。有文献报道的耳廓SCs。本综述采用预定的选择标准纳入了约47篇文章。数据从PubMed, b谷歌scholar和Science direct中提取以进行详细评论。所有纳入的研究都测试了SCs的抗真菌活性并评估了它们的作用模式。这些数据强调了不同的作用模式,如生物膜形成的扰动,细胞壁和细胞器的破坏,抑制外排和活性氧的产生等等。综上所述,SCs是有效抗真菌治疗的可行候选药物。本研究收集的信息强调需要进一步的研究,包括临床前研究和临床试验,以评估这些药物对金黄色葡萄球菌的治疗潜力。
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引用次数: 0
Advancing organ-on-chip systems: the role of microfluidics in neuro-cardiac research 推进器官芯片系统:微流体在神经心脏研究中的作用
Q2 Agricultural and Biological Sciences Pub Date : 2025-01-01 DOI: 10.1016/j.crphar.2025.100227
Maria João Ferreira , Sarah Colombani , Albin Bernardin , Alain Lacampagne , Jean-Luc Pasquié , Pedro F. Costa , Benoit Charlot , Albano C. Meli
The neuro-cardiac junction is involved in many pathological conditions in humans, but no model currently allows translational studies to investigate its role. Animal models fail to accurately represent this interaction. This review explores the role of microfluidic technologies in advancing organ-on-chip systems that simulate neuro-cardiac interactions in a controlled environment. By offering precise control over cellular environments, microfluidic platforms significantly enhance the modeling of dynamic cardiac-neural cell interactions. These systems allow the development of more accurate and functional neuro-cardiac junctions, vital for investigating cardiovascular diseases and the neuronal impact in these pathologies. While traditional animal models and co-culture techniques have their merits, they are limited in replicating human-specific physiology. Recent innovations in microfluidics, in combination with human-induced pluripotent stem cell technology, provide more physiologically relevant models and address ethical concerns regarding animal use. This review emphasizes the potential of these advanced microfluidic models in improving disease modeling, drug screening, and therapeutic strategies, ultimately advancing personalized medicine.
神经-心脏连接点与人类的许多病理状况有关,但目前还没有模型允许对其作用进行转化研究。动物模型不能准确地反映这种相互作用。这篇综述探讨了微流控技术在推进器官芯片系统中的作用,该系统在受控环境中模拟神经-心脏相互作用。通过提供对细胞环境的精确控制,微流控平台显着增强了动态心脏-神经细胞相互作用的建模。这些系统允许更准确和功能性的神经-心脏连接的发展,对于研究心血管疾病和这些病理中的神经元影响至关重要。虽然传统的动物模型和共培养技术有其优点,但它们在复制人类特定生理方面受到限制。最近微流体技术的创新与人类诱导的多能干细胞技术相结合,提供了更多与生理相关的模型,并解决了有关动物使用的伦理问题。这篇综述强调了这些先进的微流控模型在改善疾病建模、药物筛选和治疗策略方面的潜力,最终推进个性化医疗。
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引用次数: 0
The simultaneous activation of μ- and δ-opioid receptors by (−)-2S-LP2 rescues allodynia with the contribution of TGF-β1 signaling in a rat chronic constriction injury model (−)- 2s - lp2同时激活μ-和δ-阿片受体,通过TGF-β1信号的作用,在大鼠慢性收缩损伤模型中缓解异位性疼痛
Q2 Agricultural and Biological Sciences Pub Date : 2025-01-01 DOI: 10.1016/j.crphar.2025.100229
Fidilio A. , Grasso M. , Spoto S. , Varrasi S. , Al-Khrasani M. , Caraci F. , Parenti C. , Pasquinucci L.
In neuropathic pain (NP), a dysregulation of glial functions in the central and peripheral nervous systems has been described, and the balance between pro-inflammatory and anti-inflammatory mediators is lost in the transition from acute to chronic pain. This raises the possibility to resolve pain via the induction of anti-inflammatory cytokines that have a protective role against neuroinflammatory events. Transforming growth factor-β1 (TGF-β1), an anti‐inflammatory cytokine is able to counteract the development of chronic NP. Given the correlation between opioid agonists and TGF-β1 pathway, here we describe the pharmacological profile of the dual-target μ-opioid receptor (MOR)/δ-opioid receptor (DOR) agonist (−)-2S-LP2. (−)-2S-LP2, given intraperitoneally at a dose of 0.7 mg/kg, significantly mitigated mechanical allodynia induced by chronic constriction injury in rats. This antiallodynic effect was sensitive to subcutaneous (s.c.) injection of either the MOR-selective antagonist naloxonazine (NLX, 10 mg/kg) or the DOR-selective antagonist naltrindole (NTD, 3 mg/kg), alone or when combined, demonstrating that (−)-2S-LP2 interacted simultaneously with both MOR and DOR. At mRNA or protein level, a positive effect on TGF-β1 and its receptor TGFβ-R2 expression were found and (−)-2S-LP2 also modulated the expression of spinal TGF-β1 pathway via co‐targeting MOR/DOR. Thus, the dual‐target profile of the MOR/DOR agonist (−)-2S-LP2 exerts its analgesic efficacy by rescue of TGF-β1 and could represent a novel pharmacological tool able to increase anti-inflammatory cytokines in pain conditions such as NP associated with an imbalance between inflammatory and anti-inflammatory cytokines.
在神经性疼痛(NP)中,中枢和周围神经系统的神经胶质功能失调已经被描述,在从急性到慢性疼痛的过渡中,促炎和抗炎介质之间的平衡丢失。这增加了通过诱导抗炎细胞因子来解决疼痛的可能性,抗炎细胞因子对神经炎症事件具有保护作用。转化生长因子-β1 (TGF-β1)是一种抗炎细胞因子,能够抑制慢性NP的发展。鉴于阿片受体激动剂与TGF-β1通路之间的相关性,本文描述了双靶点μ-阿片受体(MOR)/δ-阿片受体(DOR)激动剂(−)-2S-LP2的药理学特征。(−)-2S-LP2以0.7 mg/kg的剂量腹腔注射,可显著减轻大鼠慢性收缩损伤引起的机械性异常痛。这种抗异动作用对皮下注射MOR选择性拮抗剂纳洛唑嗪(NLX, 10 mg/kg)或DOR选择性拮抗剂纳曲多(NTD, 3 mg/kg)均敏感,表明(−)-2S-LP2同时与MOR和DOR相互作用。在mRNA或蛋白水平上,我们发现TGF-β1及其受体TGF-β - r2的表达有正向影响,(−)-2S-LP2也通过共靶向MOR/DOR调节脊柱TGF-β1通路的表达。因此,MOR/DOR激动剂(−)-2S-LP2的双靶点特征通过挽救TGF-β1发挥其镇痛作用,可能代表一种新的药理学工具,能够增加疼痛条件下的抗炎细胞因子,如与炎症和抗炎细胞因子之间不平衡相关的NP。
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引用次数: 0
Gallic acid serves as an effective therapeutic agent of inflammatory bowel disease: Pharmacological impacts on tight junction-dependent intestinal permeability in vivo and its related intracellular signaling 没食子酸作为炎症性肠病的有效治疗剂:对体内紧密连接依赖性肠通透性及其相关细胞内信号传导的药理影响
Q2 Agricultural and Biological Sciences Pub Date : 2025-01-01 DOI: 10.1016/j.crphar.2025.100223
Apiwan Arinno , Pichayapa Sukmak , Purisha Kulworasreth , Thaniya Sricharunrat , Chutima S. Vaddhanaphuti , Pawin Pongkorpsakol
Intestinal tight junction disruption contributes to the pathogenesis of inflammatory bowel diseases (IBD). We have recently reported that gallic acid was able to enhance intestinal tight junction assembly via CaMKK-β/AMPK/SIRT-1/ERK-dependent mechanisms with unknown possible therapeutic applications in IBD. The main aims of this study are to investigate the in vivo effects of gallic acid in experimental colitis mice and to search for feasible mechanisms of action. Here, we found that gallic acid attenuated weight loss, reduced disease activity index, and reversed colon length shortening in DSS-induced colitis mice. Importantly, gallic acid also significantly increased survival rates of DSS-induced colitis mice. Based on histopathological analyses, gallic acid diminished immune cell infiltration and neutrophil activity in colitis tissues. Of particular interest, gallic acid significantly reduced gene expressions of proinflammatory cytokines, including TNF, IFN-γ, IL-1β, IL-6, and IL-8. In addition, gallic acid suppressed MLCK gene transcription and protein expression in DSS-induced colitis mice. Furthermore, gallic acid also enhanced the expression of tight junction proteins, including ZO-1 and occludin. Consistently, gallic acid reduced tight junction-dependent leak pathway permeability and was shown to increase SIRT-1 activity, AMPK, and ERK phosphorylation in colon tissues of DSS-induced colitis mice. This study not only explores anti-colitogenic impacts of gallic acid, but also sheds some light on the mechanisms of its action. According to our findings, gallic acid may be useful as an anti-colitogenic nutraceutical.
肠道紧密连接破坏有助于炎症性肠病(IBD)的发病机制。我们最近报道没食子酸能够通过CaMKK-β/AMPK/SIRT-1/ erk依赖机制增强肠紧密连接组装,但在IBD中的治疗应用尚不清楚。本研究的主要目的是研究没食子酸在实验性结肠炎小鼠体内的作用,并寻找可行的作用机制。在这里,我们发现没食子酸减轻了dss诱导的结肠炎小鼠的体重减轻,降低了疾病活动指数,并逆转了结肠长度缩短。重要的是,没食子酸还显著提高了dss诱导结肠炎小鼠的存活率。根据组织病理学分析,没食子酸降低了结肠炎组织中的免疫细胞浸润和中性粒细胞活性。特别有趣的是,没食子酸显著降低了促炎细胞因子的基因表达,包括TNF、IFN-γ、IL-1β、IL-6和IL-8。此外,没食子酸抑制dss诱导结肠炎小鼠MLCK基因转录和蛋白表达。此外,没食子酸还增强了紧密连接蛋白的表达,包括ZO-1和occludin。一致地,没食子酸降低了紧密连接依赖性泄漏通路的通透性,并在dss诱导的结肠炎小鼠结肠组织中增加了SIRT-1活性、AMPK和ERK磷酸化。本研究不仅探讨了没食子酸的抗结肠炎作用,还揭示了其作用机制。根据我们的发现,没食子酸可能是一种有用的抗结肠炎的营养保健品。
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引用次数: 0
A 10-year interval of cardiovascular effects of albuterol in asthma management: Graphical review 沙丁胺醇在哮喘治疗中心血管作用的10年间隔:图形回顾
Q2 Agricultural and Biological Sciences Pub Date : 2025-01-01 DOI: 10.1016/j.crphar.2025.100236
Ghulam H. Abbas , Faaizah Ahmed , Reda Iqbal , Fathimathul Henna , Edmon R. Khouri , Frank W.J.M. Smeenk , Sjaak Pouwels
Asthma is a widespread chronic respiratory disease that requires effective management to reduce exacerbations and improve patient outcomes. Albuterol (salbutamol), a short-acting beta-2-agonist (SABA), remains a mainstay treatment for acute symptom relief due to its rapid bronchodilatory effect. However, accumulating evidence over the past decade has raised concerns about its cardiovascular safety, particularly in vulnerable populations such as children, elderly individuals, and those with underlying cardiac conditions. This review synthesizes clinical findings from the last ten years (2015–2025) evaluating the cardiovascular effects of albuterol, including tachycardia, arrhythmias, QTc prolongation, and hypotension. Literature across PubMed, Cochrane, and Google Scholar was analyzed to assess frequency, severity, and risk factors associated with these events. Notably, intravenous administration was associated with markedly higher rates of adverse effects, while inhaled formulations remained safer with moderate risk. Pediatric patients on continuous therapy showed increased susceptibility to electrolyte imbalances and hypotension. Although alternatives like levalbuterol demonstrated a reduced cardiovascular risk profile, they were linked with increased healthcare costs and longer hospital stays. The review highlights the importance of risk stratification, personalized dosing, and enhanced monitoring, particularly in high-risk groups, to maximize the therapeutic benefits of SABAs while minimizing cardiovascular harm. Overall, the findings underscore the need for ongoing pharmacovigilance and tailored clinical decision-making when prescribing albuterol in asthma care.
哮喘是一种广泛存在的慢性呼吸系统疾病,需要有效管理以减少病情恶化并改善患者预后。沙丁胺醇(沙丁胺醇)是一种短效β -2激动剂(SABA),由于其快速的支气管扩张作用,仍然是急性症状缓解的主要治疗方法。然而,在过去的十年中,越来越多的证据引起了人们对其心血管安全性的担忧,特别是在儿童、老年人和那些有潜在心脏病的易感人群中。这篇综述综合了过去十年(2015-2025)评价沙丁胺醇心血管作用的临床发现,包括心动过速、心律失常、QTc延长和低血压。对PubMed、Cochrane和谷歌Scholar的文献进行分析,以评估与这些事件相关的频率、严重程度和风险因素。值得注意的是,静脉给药与明显较高的不良反应率相关,而吸入制剂仍然更安全,风险中等。持续治疗的儿科患者对电解质失衡和低血压的易感性增加。尽管左旋布特罗等替代药物显示出降低心血管风险的特征,但它们与医疗费用增加和住院时间延长有关。该综述强调了风险分层、个性化给药和加强监测的重要性,特别是在高危人群中,以最大限度地提高SABAs的治疗效益,同时最大限度地减少心血管危害。总的来说,研究结果强调了在哮喘治疗中处方沙丁胺醇时需要持续的药物警戒和量身定制的临床决策。
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引用次数: 0
Expression of concern regarding the article titled “Variability in the serum and tissue concentrations of pre-incisional ceftriaxone for surgery in paediatric population and outcome of surgical-site infections; An open labelled, prospective, non-randomized, analytical study” 对题为“儿科手术术前头孢曲松的血清和组织浓度的变异性和手术部位感染的结果”的文章表示关注;一项开放的、前瞻性的、非随机的、分析性的研究。”
Q2 Agricultural and Biological Sciences Pub Date : 2025-01-01
Luigino Calzetta
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引用次数: 0
Carnosine modulates Aβ-induced transcriptional aberrations in murine microglial cells
Q2 Agricultural and Biological Sciences Pub Date : 2025-01-01 DOI: 10.1016/j.crphar.2025.100221
Veronica Rivi , Giuseppe Carota , Fabio Tascedda , Johanna M.C. Blom , Filippo Caraci , Cristina Benatti , Giuseppe Caruso
Carnosine (β-alanyl-L-histidine) is an endogenous dipeptide known for its anti-inflammatory and antioxidant effects, making it a promising agent for neurodegenerative diseases like Alzheimer's disease (AD). Carnosine has shown protective effects against amyloid beta (Aβ)-induced oxidative stress and inflammation in murine microglial cells, yet its full immunomodulatory impact on these cells, particularly in terms of transcriptional regulation and cytokine interplay, remains underexplored. This study examined carnosine's effects on immune response markers in BV-2 cells exposed to Aβ oligomers. Specifically, gene expression changes in anti-inflammatory mediators (CXCL2 and IL-10) and phagocytic markers (CD11b, CD68, TNFα, IL-1β) were assessed. Notably, carnosine increased CXCL2 and IL-10 expression, promoting an anti-inflammatory response and enhancing microglial phagocytosis. Additionally, carnosine restored CX3CR1 expression, a receptor implicated in Aβ- effects in murine macrophages, and upregulated TGF-β1 and its receptor, supporting its neuroprotective role. These results underscore carnosine's potential to modulate immune responses, enhance microglial activity, and provide neuroprotection in Aβ-induced conditions. The findings highlight carnosine's therapeutic promise for AD treatment, offering a pathway for future research on its use in neurodegenerative disease interventions.
肌肽(β-丙烯酰- l-组氨酸)是一种内源性二肽,以其抗炎和抗氧化作用而闻名,使其成为治疗阿尔茨海默病(AD)等神经退行性疾病的有希望的药物。肌肽在小鼠小胶质细胞中显示出对β -淀粉样蛋白(Aβ)诱导的氧化应激和炎症的保护作用,但其对这些细胞的全面免疫调节作用,特别是在转录调节和细胞因子相互作用方面,仍未得到充分的研究。本研究检测了肌肽对暴露于Aβ低聚物的BV-2细胞免疫应答标志物的影响。具体而言,评估抗炎介质(CXCL2和IL-10)和吞噬标志物(CD11b, CD68, TNFα, IL-1β)的基因表达变化。值得注意的是,肌肽增加CXCL2和IL-10的表达,促进抗炎反应和增强小胶质细胞吞噬。此外,肌肽恢复小鼠巨噬细胞中与a β-作用有关的受体CX3CR1的表达,并上调TGF-β1及其受体,支持其神经保护作用。这些结果强调了肌肽在调节免疫反应、增强小胶质细胞活性和在a β诱导的条件下提供神经保护方面的潜力。这些发现突出了肌肽在阿尔茨海默病治疗中的治疗前景,为其在神经退行性疾病干预方面的未来研究提供了一条途径。
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引用次数: 0
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Current Research in Pharmacology and Drug Discovery
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