Medicines (Basel, Switzerland)最新文献

{"title":"Hypomyelinating Leukodystrophy 14 (HLD14)-Related UFC1 p.Arg23Gln Decreases Cell Morphogenesis: A Phenotype Reversable with Hesperetin.","authors":"Yuri Ichihara, Maho Okawa, Minori Minegishi, Hiroaki Oizumi, Masahiro Yamamoto, Katsuya Ohbuchi, Yuki Miyamoto, Junji Yamauchi","doi":"10.3390/medicines12010002","DOIUrl":"10.3390/medicines12010002","url":null,"abstract":"<p><strong>Introduction: </strong>In the central nervous system (CNS), proper interaction between neuronal and glial cells is crucial for the development of mature nervous tissue. Hypomyelinating leukodystrophies (HLDs) are a group of genetic CNS disorders characterized by hypomyelination and/or demyelination. In these conditions, genetic mutations disrupt the biological functions of oligodendroglial cells, which are responsible for wrapping neuronal axons with myelin sheaths. Among these, an amino acid mutation of the ubiquitin-fold modifier conjugating enzyme 1 (UFC1) is associated with HLD14-related disease, characterized by hypomyelination and delayed myelination in the brain. UFC1 is a critical component of the UFMylation system, functioning similarly to E2-conjugating enzymes in the ubiquitin-dependent protein degradation system.</p><p><strong>Methodology: </strong>We describe how a missense mutation in UFC1 (p.Arg23Gln) leads to the aggregation of UFC1 primarily in lysosomes in FBD-102b cells, which are undergoing oligodendroglial cell differentiation.</p><p><strong>Results: </strong>Cells with mutated UFC1 exhibit reduced Akt kinase phosphorylation and reduced expression of differentiation and myelination marker proteins. Consistently, these cells exhibit impaired morphological differentiation with a reduced ability to extend widespread membranes. Interestingly, hesperetin, a citrus flavonoid with known neuroprotective properties, was found to restore differentiation abilities in cells with the UFC1 mutation.</p><p><strong>Conclusions: </strong>These findings indicate that the HLD14-related mutation in UFC1 causes its lysosomal aggregation, impairing its morphological differentiation. Furthermore, the study highlights potential therapeutic insights into the pathological molecular and cellular mechanisms underlying HLD14 and suggests hesperetin as a promising candidate for treatment.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Pharmacokinetic Changes in Cystic Fibrosis Patients Population: Narrative Review.","authors":"Ayda Awaness, Rania Elkeeb, Sepehr Afshari, Eman Atef","doi":"10.3390/medicines12010001","DOIUrl":"10.3390/medicines12010001","url":null,"abstract":"<p><p>Cystic fibrosis (CF) is a rare genetic disorder commonly affecting multiple organs such as the lungs, pancreas, liver, kidney, and intestine. Our search focuses on the pathophysiological changes that affect the drugs' absorption, distribution, metabolism, and excretion (ADME). This review aims to identify the ADME data that compares the pharmacokinetics (PK) of different drugs in CF and healthy subjects. The published data highlight multiple factors that affect absorption, such as the bile salt precipitation and the gastrointestinal pH. Changes in CF patients' protein binding and body composition affected the drug distribution. The paper also discusses the factors affecting metabolism and renal elimination, such as drug-protein binding and metabolizing enzyme capacity. The majority of CF patients are on multidrug therapy, which increases the risk of drug-drug interactions (DDI). This is particularly true for those receiving the newly developed transmembrane conductance regulator (CFTR), as they are at a higher risk for CYP-related DDI. Our research highlights the importance of meticulously evaluating PK variations and DDIs in drug development and the therapeutic management of CF patients.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTED: Zulfiqar et al. Obesity and Frailty Syndrome in the Elderly: Prospective Study in Primary Care. <i>Medicines</i> 2022, <i>9</i>, 38.","authors":"Abrar-Ahmad Zulfiqar, Perla Habchi, Ibrahima Amadou Dembele","doi":"10.3390/medicines11080022","DOIUrl":"10.3390/medicines11080022","url":null,"abstract":"<p><p>The journal retracts the article titled \"Obesity and Frailty Syndrome in the Elderly: Prospective Study in Primary Care\" [...].</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"11 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11676820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of Aprepitant in the Management of Pediatric Patients with Cyclical Vomiting Syndrome.","authors":"Aravind Thavamani, Sindhoosha Malay, Jasmine Khatana, Sujithra Velayuthan, Senthilkumar Sankararaman","doi":"10.3390/medicines11080021","DOIUrl":"10.3390/medicines11080021","url":null,"abstract":"<p><p><b>Introduction</b>: Cyclical vomiting syndrome (CVS) is a recurrent debilitating illness characterized by intense episodes of nausea and emesis with widely varied pharmacological management across the country. Aprepitant is now increasingly used in patients with CVS. The impact of aprepitant as an abortive therapy in the readmission of pediatric patients with CVS is currently unknown. <b>Methodology</b>: We analyzed all pediatric patients with a primary diagnosis of CVS using the ICD-10 code in the Pediatric Health Information System database of the Children's Hospital Association. We evaluated the demographic data, comorbid conditions, and management details during the inpatient stay. CVS patients who received aprepitant during their inpatient hospitalization were compared with patients without aprepitant use. Seven-day readmission rate for CVS was used as the outcome variable to assess the effectiveness of the aprepitant in aborting an episode. Propensity score matching was used to match the two cohorts. <b>Results</b>: We analyzed 1775 patients of which 96 received aprepitant during the inpatient hospitalization. The aprepitant group had a more severe hospitalization course as evidenced by an increased duration of hospital stay (5 vs. 3 days) and total hospitalization costs ($11,790 vs. $6380). There were no significant differences in the 7-day (17% vs. 16%, <i>p</i> = 0.91) readmission rate and results were not altered by propensity score matching. <b>Conclusions</b>: Aprepitant use as an abortive therapy did not affect the 7-day CVS-related readmission rate. Further prospective studies are needed to explore the role of aprepitant as an abortive agent in the management of CVS in the pediatric population.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"11 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11677684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety Implications of Off-Label Medication Use in Athletes: A Narrative Review.","authors":"Vítor Silva, Ricardo Madeira, João Joaquim, Cristiano Matos","doi":"10.3390/medicines11080020","DOIUrl":"10.3390/medicines11080020","url":null,"abstract":"<p><p>In recent years, the off-label use of medications in sports has increased significantly, primarily driven by psychological and social factors. Athletes frequently misuse drugs without adequate medical supervision, relying on unreliable sources of information, which leads to improper usage and serious health risks. This narrative review analyzes literature from PubMed^® (Medline), Scopus^®, and Web of Science^® databases, focusing on studies up to December 2023, to examine the safety concerns related to off-label drug use in sports. The review presents an overview of the off-label use of pharmacological substances by athletes, focusing on both hormonal and non-hormonal drugs. Hormonal substances such as anabolic steroids and growth hormones, and non-hormonal agents like diuretics and β2-agonists, are frequently abused. These practices are associated with severe side effects, including infections, cardiovascular complications, hormonal imbalances, psychological disorders, dependence, and even cases of death. The study emphasizes the need for stronger regulation, public awareness initiatives, and preventive strategies to mitigate the health risks associated with this growing trend.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"11 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does Ortho-Substitution Enhance Cytotoxic Potencies in a Series of 3,5-Bis(benzylidene)-4-piperidones?","authors":"Subhas S Karki, Umashankar Das, Jan Balzarini, Erik De Clercq, Hiroshi Sakagami, Yoshihiro Uesawa, Praveen K Roayapalley, Jonathan R Dimmock","doi":"10.3390/medicines11080019","DOIUrl":"10.3390/medicines11080019","url":null,"abstract":"<p><p><b>Background:</b> A series of 3,5-benzylidene-4-piperidones, <b>1a</b>-<b>n</b>, were prepared to evaluate the hypothesis that the placement of different groups in the ortho-location of the aryl rings led to compounds with greater cytotoxic potencies than structural analogs. <b>Methods:</b> The bioevaluation of <b>1a</b>-<b>n</b> was undertaken using human Molt/4C8 and CEM cells as well as murine L1210 cells. Correlations were sought between the interplanar angles θ_A and θ_B and the cytotoxic potencies. A QSAR analysis was also undertaken. In order to evaluate whether these compounds demonstrated greater toxicity to neoplasms than non-malignant cells, <b>1a</b>-<b>n</b> were evaluated against HSC-2, HSC-3, HSC-4 and HL60 neoplasms as well as non-malignant HGF, HPC and HPLF cells. <b>Results:</b> A positive correlation was noted between the interplanar angle θ_A of one of the aryl rings and the adjacent olefinic linkage with IC₅₀ values in the Molt4/C8 screens. The QSAR analysis revealed a positive correlation between the Hansch pi (π) value of the aryl substituents and the IC₅₀ values of the compounds towards the Molt4/C8 and CEM cells. The dienones in series <b>1</b> demonstrated higher tumor-selective toxicity towards HSC-2, HSC-3, HSC-4 and HL-60 neoplasms than HGF, HPC and HPLF cells. <b>Conclusions:</b> The bioevaluations revealed some support for greater cytotoxic potencies to be displayed by compounds having ortho-substituents.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"11 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breathing for Two: Asthma Management, Treatment, and Safety of Pharmacological Therapy during Pregnancy.","authors":"Jovan Javorac, Dejan Živanović, Biljana Zvezdin, Vesna Mijatović Jovin","doi":"10.3390/medicines11070018","DOIUrl":"10.3390/medicines11070018","url":null,"abstract":"<p><p>The primary objectives of asthma management during pregnancy are to achieve adequate symptom control, reduce the risk of acute exacerbations, and maintain normal pulmonary function, all of which contribute to ensuring the health and well-being of both the mother and the baby. The Global Initiative for Asthma (GINA) recommends that pregnant women with asthma continue using asthma medications throughout pregnancy, as the benefits of well-controlled asthma for both the mother and fetus outweigh the potential risks of medication side effects, poorly controlled asthma, and exacerbations. The classification of asthma medications by the US Food and Drug Administration (FDA) into categories A, B, C, D, and X is no longer applied. Instead, the potential benefits and risks of each medication during pregnancy and lactation are considered individually. The use of medications to achieve good asthma control and prevent exacerbations during pregnancy is justified, encompassing inhaled corticosteroids (ICS), some leukotriene receptor antagonists (LTRA), short-acting beta-2 agonists (SABA), long-acting beta-2 agonists (LABA), short-acting muscarinic antagonists (SAMA), long-acting muscarinic antagonists (LAMA), and, recently, biological therapies, even in the absence of definitive safety data during pregnancy.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"11 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GDF15 Targeting for Treatment of Hyperemesis Gravidarum.","authors":"Jamie Thygerson, Dallin Oyler, Jackson Thomas, Brandon Muse, Benjamin D Brooks, Jessica E Pullan","doi":"10.3390/medicines11070017","DOIUrl":"10.3390/medicines11070017","url":null,"abstract":"<p><p>Nausea and vomiting during pregnancy (NVP), particularly its severe form, Hyperemesis gravidarum (HG), affects up to 70% of pregnancies and significantly impacts the quality of life for those with the condition as well as generates a great economic burden, with annual costs exceeding $1.7 billion in the United States. Despite the available treatments targeting neurotransmitters like serotonin and dopamine, many patients experience inadequate relief and suffer from severe side effects, including headaches and dizziness. Recent research has underscored the role of GDF15, a protein mainly produced by the placenta and linked to NVP symptoms. This protein, part of the TGF-<i>β</i> superfamily, has been implicated in appetite and weight regulation and is altered in those with HG due to specific genetic mutations. Addressing the challenges of delivering effective treatments, current innovations focus on targeting GDF15 to reduce symptoms while ensuring fetal safety. Promising therapeutic strategies include non-IgG immunotherapies, small peptide and molecule antagonists, and novel administration methods such as transdermal patches. These approaches aim to optimize dosage and reduce adverse effects. The effective development and testing of these treatments necessitate advanced animal models that closely resemble human pregnancy physiology, highlighting the need for further research and funding. This ongoing research holds significant potential to improve the clinical outcomes for HG patients and decrease the economic impact on healthcare systems, urging a dedicated response from the scientific and medical communities to advance these promising treatments.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"11 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering Mechanisms, Prevention Strategies, Management Plans, Medications, and Research Techniques for Strokes in Systemic Lupus Erythematosus.","authors":"Ola A Al-Ewaidat, Moawiah M Naffaa","doi":"10.3390/medicines11070015","DOIUrl":"10.3390/medicines11070015","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is an autoimmune rheumatic condition characterized by an unpredictable course and a wide spectrum of manifestations varying in severity. Individuals with SLE are at an increased risk of cerebrovascular events, particularly strokes. These strokes manifest with a diverse range of symptoms that cannot be solely attributed to conventional risk factors, underscoring their significance among the atypical risk factors in the context of SLE. This complexity complicates the identification of optimal management plans and the selection of medication combinations for individual patients. This susceptibility is further complicated by the nuances of neuropsychiatric SLE, which reveals a diverse array of neurological symptoms, particularly those associated with ischemic and hemorrhagic strokes. Given the broad range of clinical presentations and associated risks linking strokes to SLE, ongoing research and comprehensive care strategies are essential. These efforts are critical for improving patient outcomes by optimizing management strategies and discovering new medications. This review aims to elucidate the pathological connection between SLE and strokes by examining neurological manifestations, risk factors, mechanisms, prediction and prevention strategies, management plans, and available research tools and animal models. It seeks to explore this medical correlation and discover new medication options that can be tailored to individual SLE patients at risk of stroke.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"11 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine Storm in COVID-19: Insight into Pathological Mechanisms and Therapeutic Benefits of Chinese Herbal Medicines.","authors":"Qingyuan Yu, Xian Zhou, Rotina Kapini, Anthony Arsecularatne, Wenting Song, Chunguang Li, Yang Liu, Junguo Ren, Gerald Münch, Jianxun Liu, Dennis Chang","doi":"10.3390/medicines11070014","DOIUrl":"10.3390/medicines11070014","url":null,"abstract":"<p><p>Cytokine storm (CS) is the main driver of SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) in severe coronavirus disease-19 (COVID-19). The pathological mechanisms of CS are quite complex and involve multiple critical molecular targets that turn self-limited and mild COVID-19 into a severe and life-threatening concern. At present, vaccines are strongly recommended as safe and effective treatments for preventing serious illness or death from COVID-19. However, effective treatment options are still lacking for people who are at the most risk or hospitalized with severe disease. Chinese herbal medicines have been shown to improve the clinical outcomes of mild to severe COVID-19 as an adjunct therapy, particular preventing the development of mild to severe ARDS. This review illustrates in detail the pathogenesis of CS-involved ARDS and its associated key molecular targets, cytokines and signalling pathways. The therapeutic targets were identified particularly in relation to the turning points of the development of COVID-19, from mild symptoms to severe ARDS. Preclinical and clinical studies were reviewed for the effects of Chinese herbal medicines together with conventional therapies in reducing ARDS symptoms and addressing critical therapeutic targets associated with CS. Multiple herbal formulations, herbal extracts and single bioactive phytochemicals with or without conventional therapies demonstrated strong anti-CS effects through multiple mechanisms. However, evidence from larger, well-designed clinical trials is lacking and their detailed mechanisms of action are yet to be well elucidated. More research is warranted to further evaluate the therapeutic value of Chinese herbal medicine for CS in COVID-19-induced ARDS.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"11 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11270433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}