Medicinal Research Reviews最新文献_第2页

Spatiotemporal Control Over Circadian Rhythms With Light. 光对昼夜节律的时空控制。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2025-01-05 DOI: 10.1002/med.22099

Dušan Kolarski, Wiktor Szymanski, Ben L Feringa

{"title":"Spatiotemporal Control Over Circadian Rhythms With Light.","authors":"Dušan Kolarski, Wiktor Szymanski, Ben L Feringa","doi":"10.1002/med.22099","DOIUrl":"https://doi.org/10.1002/med.22099","url":null,"abstract":"Circadian rhythms are endogenous biological oscillators that synchronize internal physiological processes and behaviors with external environmental changes, sustaining homeostasis and health. Disruption of circadian rhythms leads to numerous diseases, including cardiovascular and metabolic diseases, cancer, diabetes, and neurological disorders. Despite the potential to restore healthy rhythms in the organism, pharmacological chronotherapy lacks spatial and temporal resolution. Addressing this challenge, chrono-photopharmacology, the approach that employs small molecules with light-controlled activity, enables the modulation of circadian rhythms when and where needed. Two approaches-relying on irreversible and reversible drug activation-have been proposed for this purpose. These methodologies are based on photoremovable protecting groups and photoswitches, respectively. Designing photoresponsive bioactive molecules requires meticulous structural optimization to obtain the desired chemical and photophysical properties, and the design principles, detailed guidelines and challenges are summarized here. In this review, we also analyze all the known circadian modulators responsive to light and dissect the rationale following their construction and application to control circadian biology from the protein level to living organisms. Finally, we present the strength of a reversible approach in allowing the modulation of the circadian period and the phase.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

α-Synuclein in Parkinson's Disease: From Bench to Bedside. α-突触核蛋白在帕金森病中的作用：从实验室到临床。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-12-20 DOI: 10.1002/med.22091

Gabriele Bellini, Vanessa D'Antongiovanni, Giovanni Palermo, Luca Antonioli, Matteo Fornai, Roberto Ceravolo, Nunzia Bernardini, Pascal Derkinderen, Carolina Pellegrini

{"title":"α-Synuclein in Parkinson's Disease: From Bench to Bedside.","authors":"Gabriele Bellini, Vanessa D'Antongiovanni, Giovanni Palermo, Luca Antonioli, Matteo Fornai, Roberto Ceravolo, Nunzia Bernardini, Pascal Derkinderen, Carolina Pellegrini","doi":"10.1002/med.22091","DOIUrl":"https://doi.org/10.1002/med.22091","url":null,"abstract":"α-Synuclein (α-syn), a pathological hallmark of PD, is emerging as a bridging element at the crossroads between neuro/immune-inflammatory responses and neurodegeneration in PD. Several evidence show that pathological α-syn accumulates in neuronal and non-neuronal cells (i.e., neurons, microglia, macrophages, skin cells, and intestinal cells) in central and peripheral tissues since the prodromal phase of the disease, contributing to brain pathology. Indeed, pathological α-syn deposition can promote neurogenic/immune-inflammatory responses that contribute to systemic and central neuroinflammation associated with PD. After providing an overview of the structure and functions of physiological α-syn as well as its pathological forms, we review current studies about the role of neuronal and non-neuronal α-syn at the crossroads between neuroinflammation and neurodegeneration in PD. In addition, we provide an overview of the correlation between the accumulation of α-syn in central and peripheral tissues and PD, related symptoms, and neuroinflammation. Special attention was paid to discussing whether targeting α-syn can represent a suitable therapeutical approach for PD.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Advances in the Delivery, Activation and Therapeutics Applications of Bioorthogonal Prodrugs. 生物正交前药的传递、活化及治疗应用研究进展。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-12-18 DOI: 10.1002/med.22095

Zhou Zhou, Yuanjun Sun, Jing Pang, Ya-Qiu Long

{"title":"Advances in the Delivery, Activation and Therapeutics Applications of Bioorthogonal Prodrugs.","authors":"Zhou Zhou, Yuanjun Sun, Jing Pang, Ya-Qiu Long","doi":"10.1002/med.22095","DOIUrl":"https://doi.org/10.1002/med.22095","url":null,"abstract":"Traditional prodrug strategies have been leveraged to overcome many inherent drawbacks of active native drugs in the drug research and development. However, endogenous stimuli such as specific microenvironment or enzymes are relied on to achieve the prodrug activation, resulting in unintended drug release and systemic toxicity. Alternatively, bioorthogonal cleavage reaction-enabled bioorthogonal prodrugs activation via exogenous triggers has emerged as a valuable approach, featuring spatiotemporally controlled drug release. Such bioorthogonal prodrug strategies would ensure targeted drug delivery and/or in situ generation, further circumventing systemic toxicity or premature elimination of active drugs. In recent years, metal-free bioorthogonal cleavage reactions with fast kinetics have boomed in the bioorthogonal prodrug design. Meanwhile, transition-metal-catalyzed and photocatalytic deprotection reactions have also been developed to trigger prodrug activation in biological systems. Besides traditional small molecule prodrugs, gasotransmitters have been successfully delivered to specific organelles or cells via bioorthogonal reactions, and nanosystems have been devised into bioorthogonal triggers as well. Herein, we present an overview of the latest advances in these bioorthogonally-uncaged prodrugs, focused on the delivery, activation and therapeutics applications.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Comparison of Radionuclide Drug Conjugates With Boron Neutron Capture Therapy: An Overview of Targeted Charged Particle Radiation Therapy. 放射性核素药物偶联物与硼中子俘获治疗的比较：靶向带电粒子放射治疗综述。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-12-17 DOI: 10.1002/med.22093

Yingjun Zhang, Paolo Coghi, Zimo Ren, Narayan S Hosmane, Yinghuai Zhu

引用次数: 0

Front Cover Image, Volume 45, Issue 1 封面图像，第45卷，第1期

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-12-13 DOI: 10.1002/med.22094

Jinyi Wang, Tingting Zhou

引用次数: 0

β₃-Adrenoceptor Agonism to Mimic the Biological Effects of Intrauterine Hypoxia: Taking Great Strides Toward a Pharmacological Artificial Placenta. β3-肾上腺素受体激动剂模拟宫内缺氧的生物效应：向药理人工胎盘迈出一大步。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-11-27 DOI: 10.1002/med.22092

Luca Filippi, Francesca Innocenti, Francesca Pascarella, Rosa Teresa Scaramuzzo, Riccardo Morganti, Paola Bagnoli, Maurizio Cammalleri, Massimo Dal Monte, Maura Calvani, Alessandro Pini

{"title":"β3-Adrenoceptor Agonism to Mimic the Biological Effects of Intrauterine Hypoxia: Taking Great Strides Toward a Pharmacological Artificial Placenta.","authors":"Luca Filippi, Francesca Innocenti, Francesca Pascarella, Rosa Teresa Scaramuzzo, Riccardo Morganti, Paola Bagnoli, Maurizio Cammalleri, Massimo Dal Monte, Maura Calvani, Alessandro Pini","doi":"10.1002/med.22092","DOIUrl":"https://doi.org/10.1002/med.22092","url":null,"abstract":"At different stages of life, from embryonic to postnatal, varying oxygen concentrations modulate cellular gene expression by enhancing or repressing hypoxia-inducible transcription factors. During embryonic/fetal life, these genes encode proteins involved in adapting to a low-oxygen environment, including the induction of specific enzymes related to glycolytic metabolism, erythropoiesis, angiogenesis, and vasculogenesis. However, oxygen concentrations fluctuate during intrauterine life, enabling the induction of tissue-specific differentiation processes. Fetal well-being is thus closely linked to the physiological benefits of a dynamically hypoxic environment. Premature birth entails the precocious exposure of the immature fetus to a more oxygen-rich environment compared to the womb. As a result, preterm newborns face a condition of relative hyperoxia, which alters the postnatal development of organs and contributes to prematurity-related diseases. However, until recently, the molecular mechanism by which high oxygen tension alters normal fetal differentiation remained unclear. In this review, we discuss the research trajectory followed by our research group, which suggests that early exposure to a relatively hyperoxic environment may impair preterm neonates due to reduced expression of the β3-adrenoceptor. Additionally, we explore how these impairments could be prevented through the pharmacological stimulation of the remaining β3-adrenoceptors. Recent preclinical studies demonstrate that pharmacological stimulation of the β3-adrenoceptor can decouple exposure to hyperoxia from its harmful effects, offering a glimpse of the possibility to recreating the conditions typical of intrauterine life, even after premature birth.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Deciphering the landscape of triple negative breast cancer from microenvironment dynamics and molecular insights to biomarker analysis and therapeutic modalities. 从微环境动力学和分子洞察到生物标记分析和治疗模式，解密三阴性乳腺癌的全貌。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-10-24 DOI: 10.1002/med.22090

Harshita Tiwari, Swati Singh, Sonal Sharma, Priyamvada Gupta, Ashish Verma, Amrit Chattopadhaya, Brijesh Kumar, Sakshi Agarwal, Rajiv Kumar, Sanjeev Kumar Gupta, Vibhav Gautam

{"title":"Deciphering the landscape of triple negative breast cancer from microenvironment dynamics and molecular insights to biomarker analysis and therapeutic modalities.","authors":"Harshita Tiwari, Swati Singh, Sonal Sharma, Priyamvada Gupta, Ashish Verma, Amrit Chattopadhaya, Brijesh Kumar, Sakshi Agarwal, Rajiv Kumar, Sanjeev Kumar Gupta, Vibhav Gautam","doi":"10.1002/med.22090","DOIUrl":"https://doi.org/10.1002/med.22090","url":null,"abstract":"Triple negative breast cancer (TNBC) displays a notable challenge in clinical oncology due to its invasive nature which is attributed to the absence of progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor (HER-2). The heterogenous tumor microenvironment (TME) of TNBC is composed of diverse constituents that intricately interact to evade immune response and facilitate cancer progression and metastasis. Based on molecular gene expression, TNBC is classified into four molecular subtypes: basal-like (BL1 and BL2), luminal androgen receptor (LAR), immunomodulatory (IM), and mesenchymal. TNBC is an aggressive histological variant with adverse prognosis and poor therapeutic response. The lack of response in most of the TNBC patients could be attributed to the heterogeneity of the disease, highlighting the need for more effective treatments and reliable prognostic biomarkers. Targeting certain signaling pathways and their components has emerged as a promising therapeutic strategy for improving patient outcomes. In this review, we have summarized the interactions among various components of the dynamic TME in TNBC and discussed the classification of its molecular subtypes. Moreover, the purpose of this review is to compile and provide an overview of the most recent data about recently discovered novel TNBC biomarkers and targeted therapeutics that have proven successful in treating metastatic TNBC. The emergence of novel therapeutic strategies such as chemoimmunotherapy, chimeric antigen receptor (CAR)-T cells-based immunotherapy, phytometabolites-mediated natural therapy, photodynamic and photothermal approaches have made a significant positive impact and have paved the way for more effective interventions.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Front Cover Image, Volume 44, Issue 6 封面图片，第 44 卷第 6 期

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-10-03 DOI: 10.1002/med.22089

Yunxiao Zhong, Xinya Zhang, Ruibing Feng, Yu Fan, Zhang Zhang, Qing-Wen Zhang, Jian-Bo Wan, Yitao Wang, Hua Yu, Guodong Li

引用次数: 0

Inside Front Cover Image, Volume 44, Issue 6 封面内页图片，第 44 卷第 6 期

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-10-03 DOI: 10.1002/med.22088

Vijay K. Boda, Nelufar Yasmen, Jianxiong Jiang, Wei Li

引用次数: 0

An overview of the progress made in research into the Mpox virus Mpox 病毒研究进展概述。