Frontiers in Pharmacology最新文献

{"title":"Case report: Acute liver failure during deferasirox therapy and the potential role of pharmacogenetics.","authors":"Belén García-Fariña, Lydia Rink, Virginia Santarini, Marco Westkemper, Christian Dohna-Schwake, Birte Möhlendick","doi":"10.3389/fphar.2024.1477755","DOIUrl":"10.3389/fphar.2024.1477755","url":null,"abstract":"<p><strong>Background and aims: </strong>A number of case reports have documented the occurrence of acute hepatic and renal toxicity during treatment with deferasirox (DFX). The precise mechanisms underlying these adverse events remain unclear, with the time to toxicity varying considerably between patients-some experiencing it within weeks of treatment initiation, while others after several years. Recent studies have underscored the association of pharmacogenetic variants in genes responsible for the metabolism and clearance of DFX (<i>ABCC2</i>, <i>ABCG2</i>, and <i>UGT1A1</i>) in the development of toxicity. We present the case of an 8-year-old patient with beta thalassemia major who developed acute hepatic failure years after the initiation of DFX therapy. After ruling out the most likely causes, we performed a pharmacogenetic analysis, which suggested a possible link between the patient's genotype and the development of toxicity.</p><p><strong>Methods: </strong>Sanger sequencing was performed for the most extensively studied single nucleotide polymorphisms (SNPs) studied associated with changes in transporter/enzyme function: <i>ABCC2</i> rs717620 (c.-24C>T), rs2273697 (c.1249G>A), rs8187710 (c.4544G>A), rs369192412 (g.99781071delG); <i>ABCG2</i> rs2231142 (c.421C>A); <i>UGT1A1 *6</i> rs4148323 (c.211G>A), <i>*28</i> rs3064744 (g.233760235TA[8]), <i>*36</i> rs3064744 (g.233760235TA[6]) and <i>*37</i> rs3064744 (g.233760235TA[9]).</p><p><strong>Results: </strong>The patient is heterozygous for two <i>ABCC2</i> variants, namely rs717620 (c.-24C>T) and rs2273697 (c.1249G>A). These variants have the potential to cause a reduction in transporter function, which could in turn result in decreased drug clearance and increased toxicity.</p><p><strong>Discussion: </strong>The precise mechanism by which toxicity developed in this case remains unclear and is likely multifactorial. However, it is probable that the presence of SNPs in the gene <i>ABCC2</i> played a substantial role. Our findings align with those of previously published reports of remarkably similar cases, where patients also exhibited genetic variants in the gene <i>ABCC2</i>.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Composition of lipid nanoparticles for targeted delivery: application to mRNA therapeutics.","authors":"Olga Vasileva, Olga Zaborova, Bogdan Shmykov, Roman Ivanov, Vasiliy Reshetnikov","doi":"10.3389/fphar.2024.1466337","DOIUrl":"10.3389/fphar.2024.1466337","url":null,"abstract":"<p><p>Today, lipid nanoparticles (LNPs) are some of the main delivery systems for mRNA-based therapeutics. The scope of LNP applications in terms of RNA is not limited to antiviral vaccines but encompasses anticancer drugs and therapeutics for genetic (including rare) diseases. Such widespread use implies high customizability of targeted delivery of LNPs to specific organs and tissues. This review addresses vector-free options for targeted delivery of LNPs, namely the influence of lipid composition of these nanoparticles on their biodistribution. In the review, experimental studies are examined that are focused on the biodistribution of mRNA or of the encoded protein after mRNA administration via LNPs in mammals. We also performed a comprehensive analysis of individual lipids' functional groups that ensure biodistribution to desired organs. These data will allow us to outline prospects for further optimization of lipid compositions of nanoparticles for targeted delivery of mRNA therapeutics.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPAG6 overexpression decreases the pro-apoptotic effect of daunorubicin in acute myeloid leukemia cells through the ROS/JNK MAPK axis in a GSTP1-dependent manner.","authors":"Jie Luo, Li Ding, Shirui Pan, Jing Luo, Haiqiu Zhao, Jiaxiu Yin, Rong Su, Jiamin Zhang, Lin Liu","doi":"10.3389/fphar.2024.1390456","DOIUrl":"10.3389/fphar.2024.1390456","url":null,"abstract":"<p><strong>Introduction: </strong>As a malignant hematological disease, the incidence of acute myeloid leukemia (AML) has exhibited an upward trend in recent years. Nevertheless, certain limitations persist in the treatment of AML. Sperm-associated antigen 6 (SPAG6) has been implicated in the onset and progression of various human cancers, with its expression levels significantly elevated in AML. Consequently, we undertook a series of experiments to investigate the role and underlying mechanisms of SPAG6 in AML cell lines.</p><p><strong>Methods: </strong>In the <i>in vitro</i> experiments of this study, DEPs and GO and KEGG enrichment analysis subsequent to SPAG6 down-regulation were detected by TMT. CCK8 was employed to determine cell viability. The levels of apoptosis and ROS were measured by flow cytometry. In the <i>in vivo</i> experiments, a xenografted tumor model was constructed, and the expression of SPAG6 and GSTP1 in tumor tissues was detected by IHC.</p><p><strong>Results: </strong>Ultimately, our findings indicated that over-expression of SPAG6 promoted cell growth and decreased reactive oxygen species (ROS) and malondialdehyde levels. Furthermore, SPAG6 knockdown was found to diminish mitochondrial membrane potential and facilitate cell apoptosis. <i>In vivo</i>, SPAG6 could also promote tumor growth, suggesting that SPAG6 may serve as a pro-tumor factor. In addition, daunorubicin (DNR) may cause oxidative stress and initiate apoptosis, resulting in oxidative damage to AML cells. However, the overexpression of SPAG6 may attenuate the efficacy of DNR. This was due to SPAG6 promoted GSTP1 expression, thereby reducing ROS levels. Simultaneously, the elevation of GSTP1 and JNK complex may reduce the expression of p-JNK and inhibit the activation of JNK pathway, which might inhibit cell apoptosis.</p><p><strong>Discussion: </strong>In conclusion, our experiments suggested that upregulated SPAG6 might mitigate the pro-apoptotic effects of DNR through ROS/JNK MAPK axis in a GSTP1-dependent manner.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem cell-derived exosomes for ischemic stroke: a conventional and network meta-analysis based on animal models.","authors":"Kangli Xu, Xiaohui Zhao, Yuxuan He, Hongxin Guo, Yunke Zhang","doi":"10.3389/fphar.2024.1481617","DOIUrl":"10.3389/fphar.2024.1481617","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;We aimed to evaluate the efficacy of stem cell-derived exosomes for treating ischemic stroke and to screen for the optimal administration strategy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We searched PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases for relevant studies published from their inception to 31 December 2023. Conventional and network meta-analyses of the routes of administration, types, and immune compatibility of stem cell-derived exosomes were performed using the cerebral infarct volume (%) and modified neurological severity score (mNSS) as outcome indicators.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 38 randomized controlled animal experiments were included. Conventional meta-analysis showed that compared with the negative control group: intravenous administration significantly reduced the cerebral infarct volume (%) and mNSS; intranasal administration significantly reduced the cerebral infarct volume (%); and intracerebral administration significantly reduced the mNSS. Adipose-derived mesenchymal stem cell-derived exosomes (ADSC-Exos), bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos), dental pulp stem cell-derived exosomes (DPSC-Exos) and neural stem cell-derived exosomes (NSC-Exos) significantly reduced the cerebral infarct volume (%) and mNSS; Endothelial progenitor cell-derived exosomes (EPC-Exos), embryonic stem cell-derived exosomes (ESC-Exos), induced pluripotent stem cell-derived exosomes (iPSC-Exos) and neural progenitor cell-derived exosomes (NPC-Exos) significantly reduced the cerebral infarct volume (%); Umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exos) significantly reduced the mNSS; and there was no significant difference between urogenital stem cell-derived exosomes (USC-Exos) and negative controls. Engineered modified exosomes had better efficacy than unmodified exosomes. Both allogeneic and xenogeneic stem cell-derived exosomes significantly reduced the cerebral infarct volume (%) and the mNSS. The network meta-analysis showed that intravenous administration was the best route of administration for reducing the cerebral infarct volume (%) and mNSS. Among the 10 types of stem cell-derived exosomes that were administered intravenously, BMSC-Exos were the best type for reducing the cerebral infarct volume (%) and the mNSS. Allogeneic exosomes had the best efficacy in reducing the cerebral infarct volume (%), whereas xenogeneic stem cell-derived exosomes had the best efficacy in reducing the mNSS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This meta-analysis, by integrating the available evidence, revealed that intravenous administration is the best route of administration, that BMSC-Exos are the best exosome type, that allogeneic exosomes have the best efficacy in reducing the cerebral infarct volume (%), and that xenogeneic exosomes have the best efficacy in reducing mNSS, which can provide options for preclinical studies. In the future, more high-qu","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights into the roles of lactylation in cancer.","authors":"Yajun Zhu, Wenhui Liu, Zhiying Luo, Feiyan Xiao, Bao Sun","doi":"10.3389/fphar.2024.1412672","DOIUrl":"10.3389/fphar.2024.1412672","url":null,"abstract":"<p><p>Lactylation, a novel discovered posttranslational modification, is a vital component of lactate function and is prevalent in a wide range of cells, interacting with both histone and non-histone proteins. Recent studies have confirmed that lactylation as a new contributor to epigenetic landscape is involved in multiple pathological processes. Accumulating evidence reveals that lactylation exists in different pathophysiological states and leads to inflammation and cancer; however, few mechanisms of lactylation have been elaborated. This review summarizes the biological processes and pathophysiological roles of lactylation in cancer, as well as discusses the relevant mechanisms and potential therapeutic targets, aiming to provide new insights for targeted cancer therapy.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of semaglutide induced adverse reactions: Insights from FAERS database and social media reviews with a focus on oral vs subcutaneous administration.","authors":"Jing Zhang, Xiaofen Wang, Yiting Zhou","doi":"10.3389/fphar.2024.1471615","DOIUrl":"10.3389/fphar.2024.1471615","url":null,"abstract":"<p><strong>Background: </strong>Compared to alternative weight-loss strategies and medications, semaglutide stands out for its convenience and efficacy, resulting in a significant increase in prescriptions and raising public safety concerns. Furthermore, the safety profiles of its oral and subcutaneous formulations require further examination.</p><p><strong>Objective: </strong>Our goal is to investigate the potential safety risks associated with semaglutide by analyzing data from the FAERS database and social media. Additionally, we aim to compare the adverse drug reaction (ADR) signals between the oral and subcutaneous administration routes of semaglutide.</p><p><strong>Methods: </strong>We collected semaglutide-related reports from the FAERS database spanning Q1 2018 to Q2 2023, and patient reviews on WebMD and AskaPatient up to 20 July 2023. Following data extraction and cleansing, we conducted descriptive analyses of demographic characteristics. Subsequently, we calculated adverse drug reaction (ADR) signals using the reporting odds ratio (ROR).</p><p><strong>Results: </strong>We identified 19,289 and 422 semaglutide-related adverse drug events (ADEs) reported in the FAERS database and online patient reviews, respectively. Gastrointestinal disorders emerged as the most commonly reported System Organ Class (SOC) in both datasets. Predominant Preferred Terms (PTs) included nausea, vomiting, and diarrhea. Serious outcomes constituted 3.07% and 2.25% of all cases for oral and subcutaneous semaglutide, respectively. At the SOC level, gastrointestinal disorders accounted for 30.19% of total ADEs in oral semaglutide, slightly surpassing the 27.76% in subcutaneous semaglutide. The median onset for gastrointestinal PTs was 4 days in both oral (Q1: 1, Q3: 32) and subcutaneous (Q1: 1, Q3: 35) formulations. Noteworthy, new serious adverse event (AE) signals were identified, including hemorrhagic diarrhea (ROR: 3.69), hepatic pain (ROR: 4.20), abnormal hormone levels (ROR: 6.51), and pancreatic failure (ROR: 36.34) in subcutaneous semaglutide, and Dupuytren's contracture (ROR: 46.85) in oral semaglutide.</p><p><strong>Conclusion: </strong>Our study delineates the safety profile of semaglutide using data from the FAERS database and social media. And identified novel ADR signals specific to oral and subcutaneous forms of semaglutide.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium danshensu modulates skeletal muscle fiber type formation and metabolism by inhibiting pyruvate kinase M1.","authors":"Yunxia Zhang, Xiaoxiao Wu, Ruoqi Li, Mengru Sui, Guoyin Li, Shuhua Fan, Mingsheng Yang, Qiuping Liu, Xiaomeng Liu, Changjing Wu, Lili Li","doi":"10.3389/fphar.2024.1467620","DOIUrl":"10.3389/fphar.2024.1467620","url":null,"abstract":"<p><p>Sodium Danshensu (SDSS) is extracted from <i>Salvia miltiorrhiza</i> and has many pharmacological effects. However, little is known about its effects on muscle fiber formation and metabolism. Here, we aimed to investigated the role and molecular mechanisms of SDSS in modulating the formation of skeletal muscle fiber. C2C12 cells were incubated in differentiation medium with or without SDSS for 4 days. C57BL/6 mice were orally administered SDSS by gavage once a day for 8 weeks. Grip strength, treadmill, muscle weight, western blotting, qPCR, immunofluorescence staining and H&E staining were performed. SDSS target proteins were searched through drug affinity responsive target stability (DARTS) and mass spectrometry analysis. Furthermore, molecular docking was carried out for Pyruvate kinase M1 (PKM1). The effect of PKM1 on myosin heavy chain (<i>MyHCs</i>) gene expression was verified by knockdown of PKM1 experiment. SDSS induced oxidative muscle fiber-related gene expression, and inhibited glycolytic fiber-related gene expression in C2C12 cells. Muscle mass, the percentage of slow oxidative fibers, succinic dehydrogenase activity, muscle endurance, glucose tolerance, and the expression of the <i>MyHC1</i> and <i>MyHC2a</i> genes increased while <i>MyHC2b</i> expression, lactate dehydrogenase activity, and the percentage of glycolytic muscle fibers decreased in SDSS-treated mice. Mechanistically, SDSS bound to the pyruvate kinase PKM1 and significantly repressed its activity. PKM1 inhibited <i>MyH</i>C1 and <i>MyHC2</i>a expression but promoted <i>MyHC2b</i> expression. SDSS also significantly attenuated the effects of PKM1 on muscle fiber-related gene expression in C2C12 cells. Our findings indicate that SDSS promotes muscle fiber transformation from the glycolytic type to the oxidative type by inhibiting PKM1 activity, which provide a new idea for treating muscle atrophy, muscle metabolism diseases and improving animal meat production.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the effects of moxibustion on cognitive function in rats with multiple cerebral infarctions from the perspective of glial vascular unit repairing.","authors":"Jingji Wang, Kunrui Du, Chang Liu, Xiaoyu Chen, Wenming Ban, Guoqi Zhu, Jun Yang","doi":"10.3389/fphar.2024.1428907","DOIUrl":"10.3389/fphar.2024.1428907","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore the effect of moxibustion at Governor Vessel (GV) acupoints, including Baihui (GV 20), Shenting (GV 24) and Dazhui (GV 14) for 14 days on glial vascular unit (GVU) in rats with multiple microinfarctions (MMI), and to explore its action mechanism.</p><p><strong>Methods: </strong>The effect and mechanism of moxibustion on vascular dementia (VD) were studied in MMI rats by means of behavioral and molecular biology experiments.</p><p><strong>Results: </strong>Rats receiving MMI showed impairment of memory function, reduction of cerebral blood flow, damage of blood-brain barrier (BBB) integrity and increased brain mass. MMI also increased neuronal degeneration in the hippocampus. Notably, levels of glial fibrillary acidic protein (GFAP) and complement component 3 significantly increased, but those of Connexin43 (CX43) and platelet derived growth factor receptor β (PDGFRβ) significantly decreased in the hippocampus of the rats receiving MMI. Moxibustion, as well as oxiracetam (ORC) treatment improved memory function and neuronal degeneration, ameliorated BBB integrity, increased cerebral blood flow and decreased brain mass. In addition, moxibustion as well as oxiracetam (ORC) treatment reduced the decrease of CX43 protein and increased PDGFRβ protein level in the hippocampus of MMI rats. Moreover, moxibustion treatment reversed MMI-induced increase of the GFAP/CX43 ratio in vascular structural units. Importantly, after PDGFRβ inhibition, VD rats treated with moxibustion had impaired learning and memory, decreased cerebral blood flow, and BBB disruption.</p><p><strong>Conclusion: </strong>Moxibustion treatment at various GV acupoints improved cerebral blood flow and repaired BBB function in rats with MMI, likely through protecting GVU.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green rush and red warnings: Retrospective chart review of adverse events of interactions between cannabinoids and psychotropic drugs.","authors":"Adrian Andrzej Chrobak, Jarosław Woroń, Marcin Siwek","doi":"10.3389/fphar.2024.1500312","DOIUrl":"10.3389/fphar.2024.1500312","url":null,"abstract":"<p><strong>Aim: </strong>Our objective was to systematically assess the prevalence and clinical features of adverse events related to interactions between cannabinoids and psychotropic drugs through a retrospective chart review.</p><p><strong>Methodology: </strong>1586 adverse event reports were assessed. Cases included in the analysis showed a high probability of a causal relationships between cannabinoid-psychotropic drug interactions and adverse events. Data extracted included age, sex, psychotropic drug, cannabinoid products, other medications, and the clinical outcomes and mechanisms of these interactions.</p><p><strong>Results: </strong>Cannabinoids were involved in 8% of adverse events associated with the concomitant use of psychotropic drugs and other preparations. We identified 20 reports in which side effects presented a causal relationship with the use of psychotropic drugs and cannabinoids. Preparations containing 18% or more tetrahydrocannabinol (THC), presented significant side effects with the following antidepressants: mianserine (restless legs syndrome, urogenital pain, ventricular tachycardia), mirtazapine (pancreatitis, hyperhidrosis, arthralgia), quetiapine (myocarditis, renal failure, bradycardia, sialorrhea), haloperidol (ventricular arrhythmia, prolonged QTc), aripiprazole (prolonged QTc), ventricular tachycardia) and cariprazine (stomach pain, hepatotoxicity), sertraline (ataxia, hyperactivity, coma, hallucinations, anxiety, agitation, tachycardia, panic attacks, disorientation, headache, dizziness, blurry vision, severe emesis, xerostomia, dry eyes), trazodone (disorientation, memory impairment, sedation), fluvoxamine (tachycardia, tachypnoea, dysarthria, auditory hallucinations). Two out of 20 reports (10%) analyzed in our study was related with the simultaneous use of cannabidiol (CBD) oil and sertraline. Concomitant use of those substances was associated with the adverse events in form of diarrhea, emesis, fever and severe fatigue.</p><p><strong>Conclusion: </strong>Clinicians need to closely monitor adverse events resulting from the combined use of cannabinoids and psychotropic medications. The accumulation of side effects and pharmacokinetic interactions (including CYP and p-glycoprotein inhibition) between these drugs can lead to clinically significant adverse outcomes.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nervonic acid as novel therapeutics initiates both neurogenesis and angiogenesis for comprehensive wound repair and healing.","authors":"Yu-Da Liu, Xiao Peng, Hao-Ran Chen, Xue-Song Liu, Li-Hua Peng","doi":"10.3389/fphar.2024.1487183","DOIUrl":"10.3389/fphar.2024.1487183","url":null,"abstract":"<p><p>Rapid tissue reconstruction in acute and chronic injuries are challengeable, the inefficient repair mainly due to the difficulty in simultaneous promoting the regeneration of peripheral nerves and vascular, which are closely related. Main clinical medication strategy of tissue repair depends on different cytokines to achieve nerves, blood vessels or granulation tissue regeneration, respectively. However, their effect is still limited to single aspect with biorisk exists upon long-time use. Herein, for the first time, we have demonstrated that NA isolated from <i>Malania oleifera</i> has potential to simultaneously promote both neurogenesis and angiogenesis <i>in vitro</i> and <i>in vivo</i>. First, NA was identified by NMR and FTIR structural characterization analysis. In a model of oxidative stress in neural cells induced by hydrogen peroxide, the cells viability of RSC96 and PC12 were protected from oxidative stress injury by NA. Similarly, based on the rat wound healing model, effective blood vessel formation and wound healing can be observed in tissue staining under NA treatment. In addition, according to the identification of nerve and vascular related markers in the wound tissue, the mechanism of NA promoting nerve regeneration lies in the upregulation of the secretion NGF, NF-200 and S100 protein, and NA treatment was also able to up-regulate VEGF and CD31 to directly promote angiogenesis during wound healing. This study provides an important candidate drug molecules for acute or chronic wound healing and nerve vascular synchronous regeneration.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}