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Enhanced Cerebral Hemodynamics and Cognitive Function Via Knockout of Dual-Specificity Protein Phosphatase 5. 通过敲除双特异性蛋白磷酸酶5增强脑血流动力学和认知功能。
Pub Date : 2023-01-01 Epub Date: 2023-05-12 DOI: 10.26502/fjppr.070
Huawei Zhang, Jane J Border, Xing Fang, Yedan Liu, Chengyun Tang, Wenjun Gao, Shaoxun Wang, Seung Min Shin, Ya Guo, Chao Zhang, Ezekiel Gonzalez-Fernandez, Hongwei Yu, Peng Sun, Richard J Roman, Fan Fan

Alzheimer's Disease (AD) and Alzheimer's Disease-Related Dementias (ADRD) are neurodegenerative disorders. Recent studies suggest that cerebral hypoperfusion is an early symptom of AD/ADRD. Dual-specificity protein phosphatase 5 (DUSP5) has been implicated in several pathological conditions, including pulmonary hypertension and cancer, but its role in AD/ADRD remains unclear. The present study builds on our previous findings, demonstrating that inhibition of ERK and PKC leads to a dose-dependent dilation of the middle cerebral artery and penetrating arteriole, with a more pronounced effect in Dusp5 KO rats. Both ERK and PKC inhibitors resulted in a significant reduction of myogenic tone in vessels from Dusp5 KO rats. Dusp5 KO rats exhibited stronger autoregulation of the surface but not deep cortical cerebral blood flow. Inhibition of ERK and PKC significantly enhanced the contractile capacity of vascular smooth muscle cells from both strains. Finally, a significant improvement in learning and memory was observed in Dusp5 KO rats 24 hours after initial training. Our results suggest that altered vascular reactivity in Dusp5 KO rats may involve distinct mechanisms for different vascular beds, and DUSP5 deletion could be a potential therapeutic target for AD/ADRD. Further investigations are necessary to determine the effects of DUSP5 inhibition on capillary stalling, blood-brain barrier permeability, and neurodegeneration in aging and disease models.

阿尔茨海默病(AD)和阿尔茨海默病相关痴呆症(ADRD)是神经退行性疾病。最近的研究表明,脑灌注不足是AD/ARD的早期症状。双特异性蛋白磷酸酶5(DUSP5)与多种病理状况有关,包括肺动脉高压和癌症,但其在AD/ADD中的作用尚不清楚。本研究建立在我们之前的研究结果的基础上,证明ERK和PKC的抑制导致大脑中动脉和穿透小动脉的剂量依赖性扩张,在Dusp5 KO大鼠中具有更显著的作用。ERK和PKC抑制剂均导致Dusp5 KO大鼠血管中肌源性张力的显著降低。Dusp5-KO大鼠表现出更强的皮层表面而非深层脑血流的自动调节。ERK和PKC的抑制显著增强了两种菌株血管平滑肌细胞的收缩能力。最后,在初次训练后24小时,在Dusp5 KO大鼠中观察到学习和记忆的显著改善。我们的研究结果表明,Dusp5 KO大鼠血管反应性的改变可能涉及不同血管床的不同机制,Dusp5缺失可能是AD/ADD的潜在治疗靶点。需要进一步研究DUSP5抑制对衰老和疾病模型中毛细血管停滞、血脑屏障通透性和神经退行性变的影响。
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引用次数: 0
Analgesic, Anti-inflammatory, and Antioxidant potential of S-adenosyl L-Methionine on Nitroglycerine induced Migraine in mice Models s -腺苷- l -蛋氨酸对硝酸甘油诱导的小鼠偏头痛模型的镇痛、抗炎和抗氧化作用
Pub Date : 2023-01-01 DOI: 10.26502/fjppr.067
S. Jalgaonkar, R. Tripathi, Nishtha Khatri, Rachana Patankar, S. Gajbhiye, Mohsin Sayyed, A. Shankar
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引用次数: 0
Vonoprazan-Based versus Esomeprazole-Based Triple Therapy for Helicobacter Pylori: A Randomized Trial 以伏诺哌赞为基础的三联疗法与以埃索美拉唑为基础的三联疗法治疗幽门螺杆菌的随机试验
Pub Date : 2023-01-01 DOI: 10.26502/fjppr.078
Yasser A. Abdelghani, Mahmoud M. Moussa
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引用次数: 0
Estimating Vaccine-Preventable COVID-19 Deaths Among Adults Under Counterfactual Vaccination Scenarios in The United States: A Modeling Study Using Observational Data 在美国反事实疫苗接种情景下估计疫苗可预防的COVID-19成人死亡:一项使用观察数据的建模研究
Pub Date : 2023-01-01 DOI: 10.26502/fjppr.079
Ming Zhong, Tamara Glazer, Meghana Kshirsagar, Richard Johnston, Rahul Dodhia, Allen Kim, Divya Michael, Santiago Salcido, Sameer Nair-Desai, Thomas C. Tsai, Stefanie Friedhoff, William B Weeks, Juan M. Lavista
Introduction: In early 2021, effective SARS-CoV-2 (COVID-19) vaccines became available in the United States; by mid-April 2021, vaccine availability outstripped demand, daily vaccination rates peaked, and COVID-19 vaccines were found highly effective in adult populations. Accurate estimates of the number of vaccine-preventable deaths had higher vaccination rates been attained could have helped local policymakers and possibly persuaded more to get vaccinated.
2021年初,有效的SARS-CoV-2 (COVID-19)疫苗在美国上市;到2021年4月中旬,疫苗供应超过需求,每日疫苗接种率达到峰值,COVID-19疫苗在成年人群中非常有效。如果达到更高的疫苗接种率,对疫苗可预防死亡人数的准确估计可能有助于当地政策制定者,并可能说服更多人接种疫苗。
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引用次数: 0
Supramolecular Chemistry: Unveiling the Fascinating World of Non-Covalent Interactions and Complex Assemblies 超分子化学:揭开非共价相互作用和复杂组装的迷人世界
Pub Date : 2023-01-01 DOI: 10.26502/fjppr.075
Shreya Talreja, Shashank Tiwari
Supramolecular chemistry is a captivating and interdisciplinary field that explores the interactions between molecules to form complex and functional assemblies through non-covalent forces. This review paper presents an in-depth exploration of the fundamental concepts, supramolecular assemblies and structures, applications in nanotechnology and biology, as well as challenges and future perspectives in supramolecular chemistry. The paper begins by elucidating the fundamental principles of supramolecular chemistry, emphasizing the significance of weak, non-covalent interactions such as hydrogen bonding, van der Waals forces, and π-π interactions. Molecular recognition, self-assembly, and host-guest interactions are highlighted as key concepts shaping the field. Subsequently, the review delves into various supramolecular assemblies and structures, showcasing the diversity of nanoscale architectures that arise from self-assembly processes. From nanotubes and nanofibers to metal-organic frameworks and dynamic supramolecular systems, each structure's properties and potential applications are explored. The application of supramolecular chemistry in nanotechnology and biology is a central focus of the paper. It covers the design of supramolecular materials for drug delivery, nanoelectronics, nanosensors, and biomimetic systems. Additionally, the integration of supramolecular approaches in biology, including molecular recognition, enzyme mimics, and bioimaging, is discussed in detail. Furthermore, the challenges faced by supramolecular chemistry, such as predictability, stability, and scalability, are addressed. The paper also looks into the future perspectives of the field, envisioning adaptive materials, supramolecular machines, and data-driven design as exciting prospects. Overall, this comprehensive review offers a thorough understanding of the captivating world of supramolecular chemistry and its potential to revolutionize various scientific and technological domains. Through interdisciplinary efforts and a focus on sustainability, supramolecular chemistry holds promise for addressing real-world challenges and shaping a future defined by innovative materials and transformative applications.
超分子化学是一个迷人的跨学科领域,它探索分子之间的相互作用,通过非共价力形成复杂的功能组装。本文综述了超分子化学的基本概念、超分子组装和结构、在纳米技术和生物学中的应用,以及超分子化学面临的挑战和未来的展望。本文首先阐述了超分子化学的基本原理,强调了弱非共价相互作用的重要性,如氢键、范德华力和π-π相互作用。分子识别、自组装和主客互动被强调为塑造该领域的关键概念。随后,该综述深入研究了各种超分子组装和结构,展示了自组装过程中产生的纳米级结构的多样性。从纳米管和纳米纤维到金属有机框架和动态超分子体系,探索了每种结构的性质和潜在应用。超分子化学在纳米技术和生物学中的应用是本文的中心焦点。它涵盖了用于药物输送的超分子材料的设计,纳米电子学,纳米传感器和仿生系统。此外,还详细讨论了生物学中超分子方法的整合,包括分子识别,酶模拟和生物成像。此外,还解决了超分子化学面临的挑战,如可预测性、稳定性和可扩展性。论文还展望了该领域的未来前景,展望了自适应材料、超分子机器和数据驱动设计等令人兴奋的前景。总的来说,这篇全面的综述提供了对超分子化学的迷人世界的透彻理解及其在各种科学和技术领域的革命性潜力。通过跨学科的努力和对可持续性的关注,超分子化学有望解决现实世界的挑战,塑造一个由创新材料和变革应用定义的未来。
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引用次数: 0
Characterization of Mitotic Phenotypes Associated with a MYC Synthetic Lethal Compound 与MYC合成致死化合物相关的有丝分裂表型的表征
Pub Date : 2023-01-01 DOI: 10.26502/fjppr.082
Qiong Shi
Therapeutic targeting of MYC directly has proven difficult, prompting indirect strategies using a synthetic lethal drug. Here, we characterize one such drug dimethylfasudil (diMF), a rho-associated protein kinase (ROCK) inhibitor. But this diMF activity is not linked to the synthetic lethal interaction with MYC. Instead, this compound induced multiple cell cycle-related liabilities. These included the early mitotic arrest of cycling cells followed by mitotic catastrophe and the induction of polyploidy in cells that do manage to pass through mitosis. As early as prometaphase, we noted diminished staining for BUB1 kinase, which binds to kinetochores and regulates the mitotic spindle checkpoint and chromosome congression. Kinetochore proteins, such as Centromere Protein F (CENP-F), failed to localize at kinetochores in early mitosis, confirming a deficit in centromere assembly. This, presumably, contributed to the development of anomalies in chromosome segregation in cells treated with diMF. In anaphase cells, the protein regulator of cytokinesis 1 (PRC1), failed to be recruited to the midzone, leading to a cascade of defects that included failed recruitment of the chromosomal passenger protein complex, the central spindlin complex, and polo-like-kinase 1 (PLK1). These observations correlate well with the cell death induced by diMF, which may serve as a prototype MYC synthetic lethal compound to explore synthetic lethal therapy or as a scaffold upon which to build superior compounds. The phenotypes described here serve as examples of MYC synthetic lethal drug effects that can be used to explore and maximize drug discovery programs.
直接靶向治疗MYC已被证明是困难的,因此需要使用合成致死药物的间接策略。在这里,我们描述了一种这样的药物二甲法舒地尔(diMF),一种rho相关蛋白激酶(ROCK)抑制剂。但这种diMF活性与MYC的合成致死相互作用无关。相反,这种化合物引起了多种细胞周期相关的缺陷。这些包括循环细胞的早期有丝分裂停滞,随后是有丝分裂灾难,以及在设法通过有丝分裂的细胞中诱导多倍体。早在早期中期,我们就注意到BUB1激酶的染色减少,BUB1激酶结合着丝点并调节有丝分裂纺锤体检查点和染色体聚集。着丝粒蛋白,如着丝粒蛋白F (CENP-F),在有丝分裂早期未能定位于着丝粒,证实了着丝粒组装的缺陷。据推测,这导致了用diMF处理的细胞中染色体分离异常的发生。在后期细胞中,细胞分裂1 (PRC1)的蛋白调节因子不能被募集到中间区,导致一系列缺陷,包括染色体乘客蛋白复合物、中央纺锤子复合物和polo样激酶1 (PLK1)的募集失败。这些观察结果与diMF诱导的细胞死亡密切相关,diMF可以作为MYC合成致死化合物的原型,用于探索合成致死疗法或作为构建优质化合物的支架。这里描述的表型作为MYC合成致死药物效应的例子,可用于探索和最大化药物发现计划。
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引用次数: 0
Effects of Fruits of Aqueous Extract of Sarcocephalus Latifolius B. on Gentamicin-Induced Nephrotoxicity in Rats 大脑瘤水提物果实对庆大霉素所致大鼠肾毒性的影响
Pub Date : 2023-01-01 DOI: 10.26502/fjppr.066
D. Leonard, Ballo Mahamadou, Soudré Albert, T. Basile, Bah Sekou, B. Balé
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引用次数: 2
Systems Pharmacology and Molecular Docking Reveals the Potential Beneficial effect of Rabdosia serra in Treating liver Cancer 系统药理学与分子对接揭示serdosia serra治疗肝癌的潜在有益作用
Pub Date : 2023-01-01 DOI: 10.26502/fjppr.077
Xinhui Niu, Changsheng Dong, Ismael Obaidi, Siying Chen, Junying Liu
,
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引用次数: 0
Clinical Significance of Human Herpesvirus 6 and 7 Infection in a Tertiary Hospital: a Case-Control Study 某三级医院6、7型人疱疹病毒感染的临床意义:病例-对照研究
Pub Date : 2023-01-01 DOI: 10.26502/fjppr.080
Pablo Borque, Juan Carlos Galán, Beatriz Romero, Francesca Gioia, Rosa Escudero, Pilar Martín-Dávila Santiago Moreno, Jesús Fortún
Background: Human herpesviruses (HHV)-6 and HHV-7 are ubiquitous viruses with a global seroprevalence of around 90%, but their pathogenic significance remains unclear.
背景:人类疱疹病毒(HHV)-6和HHV-7是普遍存在的病毒,全球血清阳性率约为90%,但其致病意义尚不清楚。
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引用次数: 0
A Framework on Developing an Integrative Medicine Clinical Practice Guideline (CPG) for Systemic Lupus erythematosus (SLE) with Comorbidities Management in Hong Kong 香港制定系统性红斑狼疮(SLE)及合并症管理的中西医结合临床实践指南(CPG)框架
Pub Date : 2023-01-01 DOI: 10.26502/fjppr.085
Yuanyuan Chen, Philip Hei Li, Cheng Zhang, Ning Wang, Yibin Feng, Che-Shing Lau
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引用次数: 0
期刊
Journal of pharmacy and pharmacology research
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