Medicinal Research Reviews最新文献

{"title":"Preclinical evidence using synthetic compounds and natural products indicates that AMPK represents a potential pharmacological target for the therapy of pulmonary diseases","authors":"Chao Yang,&nbsp;Limor Rubin,&nbsp;Xiyong Yu,&nbsp;Philip Lazarovici,&nbsp;Wenhua Zheng","doi":"10.1002/med.22014","DOIUrl":"10.1002/med.22014","url":null,"abstract":"<p>Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) is a highly conserved eukaryotic enzyme discovered as a key regulator of cellular energy homeostasis, with anti-inflammation, antioxidative stress, anticancer, and antifibrosis beneficial effects. AMPK is dysregulated in human pulmonary diseases such as acute lung injury, nonsmall cell lung cancer, pulmonary fibrosis, chronic obstructive pulmonary disease, and asthma. This review provides an overview of the beneficial role of natural, synthetic, and Chinese traditional medicines AMPK modulators in pulmonary diseases, and highlights the role of the AMPK signaling pathway in the lung, emphasizing the importance of finding lead compounds and drugs that can target and modulate AMPK to treat the lung diseases.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 3","pages":"1326-1369"},"PeriodicalIF":13.3,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139477258","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}

{"title":"The role of Toll-like receptors in neuropsychiatric disorders: Immunopathology, treatment, and management","authors":"Kiarash Saleki,&nbsp;Parsa Alijanizadeh,&nbsp;Nima Javanmehr,&nbsp;Nima Rezaei","doi":"10.1002/med.22012","DOIUrl":"10.1002/med.22012","url":null,"abstract":"<p>Neuropsychiatric disorders denote a broad range of illnesses involving neurology and psychiatry. These disorders include depressive disorders, anxiety, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder, autism spectrum disorders, headaches, and epilepsy. In addition to their main neuropathology that lies in the central nervous system (CNS), lately, studies have highlighted the role of immunity and neuroinflammation in neuropsychiatric disorders. Toll-like receptors (TLRs) are innate receptors that act as a bridge between the innate and adaptive immune systems via adaptor proteins (e.g., MYD88) and downstream elements; TLRs are classified into 13 families that are involved in normal function and illnesses of the CNS. TLRs expression affects the course of neuropsychiatric disorders, and is influenced during their pharmacotherapy; For example, the expression of multiple TLRs is normalized during the major depressive disorder pharmacotherapy. Here, the role of TLRs in neuroimmunology, treatment, and management of neuropsychiatric disorders is discussed. We recommend longitudinal studies to comparatively assess the cell-type-specific expression of TLRs during treatment, illness progression, and remission. Also, further research should explore molecular insights into TLRs regulation and related pathways.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 3","pages":"1267-1325"},"PeriodicalIF":13.3,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.22012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into Ganoderma fungi meroterpenoids opening a new era of racemic natural products in mushrooms","authors":"Jiao-Jiao Zhang,&nbsp;Fu-Ying Qin,&nbsp;Yong-Xian Cheng","doi":"10.1002/med.22006","DOIUrl":"10.1002/med.22006","url":null,"abstract":"<p><i>Ganoderma</i> meroterpenoids (GMs) containing 688 structures to date were discovered to have multiple remarkable biological activities. 65.6% of meroterpenoids featuring stereogenic centers from <i>Ganoderma</i> species are racemates. Further, GMs from different <i>Ganoderma</i> species seem to have their own characteristics. In this review, a comprehensive summarization of GMs since 2000 is presented, including GM structures, structure corrections, biological activities, physicochemical properties, total synthesis, and proposed biosynthetic pathways. Additionally, we especially discuss the racemic nature, species-related structural distribution, and structure–activity relationship of GMs, which will provide a likely in-house database and shed light on future studies on GMs.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 3","pages":"1221-1266"},"PeriodicalIF":13.3,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139415945","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}

{"title":"CXCR4/CXCL12 axis: “old” pathway as “novel” target for anti-inflammatory drug discovery","authors":"Liuxin Lu,&nbsp;Junjie Li,&nbsp;Xiaoying Jiang,&nbsp;Renren Bai","doi":"10.1002/med.22011","DOIUrl":"10.1002/med.22011","url":null,"abstract":"<p>Inflammation is the body's defense response to exogenous or endogenous stimuli, involving complex regulatory mechanisms. Discovering anti-inflammatory drugs with both effectiveness and long-term use safety is still the direction of researchers' efforts. The inflammatory pathway was initially identified to be involved in tumor metastasis and HIV infection. However, research in recent years has proved that the CXC chemokine receptor type 4 (CXCR4)/CXC motif chemokine ligand 12 (CXCL12) axis plays a critical role in the upstream of the inflammatory pathway due to its chemotaxis to inflammatory cells. Blocking the chemotaxis of inflammatory cells by CXCL12 at the inflammatory site may block and alleviate the inflammatory response. Therefore, developing CXCR4 antagonists has become a novel strategy for anti-inflammatory therapy. This review aimed to systematically summarize and analyze the mechanisms of action of the CXCR4/CXCL12 axis in more than 20 inflammatory diseases, highlighting its crucial role in inflammation. Additionally, the anti-inflammatory activities of CXCR4 antagonists were discussed. The findings might help generate new perspectives for developing anti-inflammatory drugs targeting the CXCR4/CXCL12 axis.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 3","pages":"1189-1220"},"PeriodicalIF":13.3,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097000","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}

{"title":"H+-slip correlated to rotor free-wheeling as cause of F1FO-ATPase dysfunction in primary mitochondrial disorders","authors":"Salvatore Nesci,&nbsp;Giovanni Romeo","doi":"10.1002/med.22013","DOIUrl":"10.1002/med.22013","url":null,"abstract":"<p>Inborn errors of metabolism are related to mitochondrial disorders caused by dysfunction of the oxidative phosphorylation (OXPHOS) system. Congenital hypermetabolism in the infant is a rare disease belonging to Luft syndrome, nonthyroidal hypermetabolism, arising from a singular example of a defect in OXPHOS. The mitochondria lose coupling of mitochondrial substrates oxidation from the ADP phosphorylation. Since Luft syndrome is due to uncoupled cell respiration responsible for deficient in ATP production that originates in the respiratory complexes, a de novo heterozygous variant in the catalytic subunit of mitochondrial F₁F_O-ATPase arises as the main cause of an autosomal dominant syndrome of hypermetabolism associated with dysfunction in ATP production, which does not involve the respiratory complexes. The F₁F_O-ATPase works as an embedded molecular machine with a rotary action using two different motor engines. The F_O, which is an integral domain in the membrane, dissipates the chemical potential difference for H⁺, a proton motive force (Δ<i>p</i>), across the inner membrane to generate a torsion. The F₁ domain—the hydrophilic portion responsible for ATP turnover—is powered by the molecular rotary action to synthesize ATP. The structural and functional coupling of F₁ and F_O domains support the energy transduction for ATP synthesis. The dissipation of Δ<i>p</i> by means of an H⁺ slip correlated to rotor free-wheeling of the F₁F_O-ATPase has been discovered to cause enzyme dysfunction in primary mitochondrial disorders. In this insight, we try to offer commentary and analysis of the molecular mechanism in these impaired mitochondria.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 3","pages":"1183-1188"},"PeriodicalIF":13.3,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.22013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139085249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emergence of machine learning force fields in drug design","authors":"Mingan Chen,&nbsp;Xinyu Jiang,&nbsp;Lehan Zhang,&nbsp;Xiaoxu Chen,&nbsp;Yiming Wen,&nbsp;Zhiyong Gu,&nbsp;Xutong Li,&nbsp;Mingyue Zheng","doi":"10.1002/med.22008","DOIUrl":"10.1002/med.22008","url":null,"abstract":"<p>In the field of molecular simulation for drug design, traditional molecular mechanic force fields and quantum chemical theories have been instrumental but limited in terms of scalability and computational efficiency. To overcome these limitations, machine learning force fields (MLFFs) have emerged as a powerful tool capable of balancing accuracy with efficiency. MLFFs rely on the relationship between molecular structures and potential energy, bypassing the need for a preconceived notion of interaction representations. Their accuracy depends on the machine learning models used, and the quality and volume of training data sets. With recent advances in equivariant neural networks and high-quality datasets, MLFFs have significantly improved their performance. This review explores MLFFs, emphasizing their potential in drug design. It elucidates MLFF principles, provides development and validation guidelines, and highlights successful MLFF implementations. It also addresses potential challenges in developing and applying MLFFs. The review concludes by illuminating the path ahead for MLFFs, outlining the challenges to be overcome and the opportunities to be harnessed. This inspires researchers to embrace MLFFs in their investigations as a new tool to perform molecular simulations in drug design.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 3","pages":"1147-1182"},"PeriodicalIF":13.3,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139085250","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}

{"title":"Metabolomics at the tumor microenvironment interface: Decoding cellular conversations","authors":"Naomi Berrell,&nbsp;Habib Sadeghirad,&nbsp;Tony Blick,&nbsp;Charles Bidgood,&nbsp;Graham R. Leggatt,&nbsp;Ken O'Byrne,&nbsp;Arutha Kulasinghe","doi":"10.1002/med.22010","DOIUrl":"10.1002/med.22010","url":null,"abstract":"<p>Cancer heterogeneity remains a significant challenge for effective cancer treatments. Altered energetics is one of the hallmarks of cancer and influences tumor growth and drug resistance. Studies have shown that heterogeneity exists within the metabolic profile of tumors, and personalized-combination therapy with relevant metabolic interventions could improve patient response. Metabolomic studies are identifying novel biomarkers and therapeutic targets that have improved treatment response. The spatial location of elements in the tumor microenvironment are becoming increasingly important for understanding disease progression. The evolution of spatial metabolomics analysis now allows scientists to deeply understand how metabolite distribution contributes to cancer biology. Recently, these techniques have spatially resolved metabolite distribution to a subcellular level. It has been proposed that metabolite mapping could improve patient outcomes by improving precision medicine, enabling earlier diagnosis and intraoperatively identifying tumor margins. This review will discuss how altered metabolic pathways contribute to cancer progression and drug resistance and will explore the current capabilities of spatial metabolomics technologies and how these could be integrated into clinical practice to improve patient outcomes.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 3","pages":"1121-1146"},"PeriodicalIF":13.3,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.22010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental structure based drug design (SBDD) applications for anti-leishmanial drugs: A paradigm shift?","authors":"Miguel Marín,&nbsp;Marta López,&nbsp;Laura Gallego-Yerga,&nbsp;Raquel Álvarez,&nbsp;Rafael Peláez","doi":"10.1002/med.22005","DOIUrl":"10.1002/med.22005","url":null,"abstract":"<p>Leishmaniasis is a group of neglected tropical diseases caused by at least 20 species of <i>Leishmania</i> protozoa, which are spread by the bite of infected sandflies. There are three main forms of the disease: cutaneous leishmaniasis (CL, the most common), visceral leishmaniasis (VL, also known as kala-azar, the most serious), and mucocutaneous leishmaniasis. One billion people live in areas endemic to leishmaniasis, with an annual estimation of 30,000 new cases of VL and more than 1 million of CL. New treatments for leishmaniasis are an urgent need, as the existing ones are inefficient, toxic, and/or expensive. We have revised the experimental structure-based drug design (SBDD) efforts applied to the discovery of new drugs against leishmaniasis. We have grouped the explored targets according to the metabolic pathways they belong to, and the key achieved advances are highlighted and evaluated. In most cases, SBDD studies follow high-throughput screening campaigns and are secondary to pharmacokinetic optimization, due to the majoritarian belief that there are few validated targets for SBDD in leishmaniasis. However, some SBDD strategies have significantly contributed to new drug candidates against leishmaniasis and a bigger number holds promise for future development.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 3","pages":"1055-1120"},"PeriodicalIF":13.3,"publicationDate":"2023-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.22005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutathione-triggered prodrugs: Design strategies, potential applications, and perspectives","authors":"Jintao Zhao,&nbsp;Xinming Li,&nbsp;Tao Ma,&nbsp;Bingbing Chang,&nbsp;Baoxin Zhang,&nbsp;Jianguo Fang","doi":"10.1002/med.22007","DOIUrl":"10.1002/med.22007","url":null,"abstract":"<p>The burgeoning prodrug strategy offers a promising avenue toward improving the efficacy and specificity of cytotoxic drugs. Elevated intracellular levels of glutathione (GSH) have been regarded as a hallmark of tumor cells and characteristic feature of the tumor microenvironment. Considering the pivotal involvement of elevated GSH in the tumorigenic process, a diverse repertoire of GSH-triggered prodrugs has been developed for cancer therapy, facilitating the attenuation of deleterious side effects associated with conventional chemotherapeutic agents and/or the attainment of more efficacious therapeutic outcomes. These prodrug formulations encompass a spectrum of architectures, spanning from small molecules to polymer-based and organic–inorganic nanomaterial constructs. Although the GSH-triggered prodrugs have been gaining increasing interests, a comprehensive review of the advancements made in the field is still lacking. To fill the existing lacuna, this review undertakes a retrospective analysis of noteworthy research endeavors, based on a categorization of these molecules by their diverse recognition units (i.e., disulfides, diselenides, Michael acceptors, and sulfonamides/sulfonates). This review also focuses on explaining the distinct benefits of employing various chemical architecture strategies in the design of these prodrug agents. Furthermore, we highlight the potential for synergistic functionality by incorporating multiple-targeting conjugates, theranostic entities, and combinational treatment modalities, all of which rely on the GSH-triggering. Overall, an extensive overview of the emerging field is presented in this review, highlighting the obstacles and opportunities that lie ahead. Our overarching goal is to furnish methodological guidance for the development of more efficacious GSH-triggered prodrugs in the future. By assessing the pros and cons of current GSH-triggered prodrugs, we expect that this review will be a handful reference for prodrug design, and would provide a guidance for improving the properties of prodrugs and discovering novel trigger scaffolds for constructing GSH-triggered prodrugs.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 3","pages":"1013-1054"},"PeriodicalIF":13.3,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138883759","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}

{"title":"Advances in machine intelligence-driven virtual screening approaches for big-data","authors":"Neeraj Kumar,&nbsp;Vishal Acharya","doi":"10.1002/med.21995","DOIUrl":"10.1002/med.21995","url":null,"abstract":"<p>Virtual screening (VS) is an integral and ever-evolving domain of drug discovery framework. The VS is traditionally classified into ligand-based (LB) and structure-based (SB) approaches. Machine intelligence or artificial intelligence has wide applications in the drug discovery domain to reduce time and resource consumption. In combination with machine intelligence algorithms, VS has emerged into revolutionarily progressive technology that learns within robust decision orders for data curation and hit molecule screening from large VS libraries in minutes or hours. The exponential growth of chemical and biological data has evolved as “big-data” in the public domain demands modern and advanced machine intelligence-driven VS approaches to screen hit molecules from ultra-large VS libraries. VS has evolved from an individual approach (LB and SB) to integrated LB and SB techniques to explore various ligand and target protein aspects for the enhanced rate of appropriate hit molecule prediction. Current trends demand advanced and intelligent solutions to handle enormous data in drug discovery domain for screening and optimizing hits or lead with fewer or no false positive hits. Following the big-data drift and tremendous growth in computational architecture, we presented this review. Here, the article categorized and emphasized individual VS techniques, detailed literature presented for machine learning implementation, modern machine intelligence approaches, and limitations and deliberated the future prospects.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 3","pages":"939-974"},"PeriodicalIF":13.3,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138827374","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}